Beyond Genomics - Targeting the Epigenome in Diffuse Large B-Cell Lymphoma

Publication date: Available online 9 August 2017
Source:Cancer Treatment Reviews
Author(s): Andrea Kühnl, David Cunningham, Ian Chau
After decades of intense research on genetic alterations in cancer and successful implementation of genetically-based targeted therapies, the field of cancer epigenetics is only beginning to be fully recognized. The discovery of frequent mutations in genes modifying the epigenome in diffuse large B-cell lymphoma (DLBCL) has highlighted the outstanding role of epigenetic deregulation in this disease. Identification of epigenetically-driven DLBCL subgroups and development of novel epigenetic drugs have rapidly advanced. However, further insights are needed into the biological consequences of epigenetic alterations and the possibility of restoring the aberrant epigenome with specific therapies to bring this treatment concept further into clinical practice. This review will summarize the main epigenetic changes found in DLBCL and their potential for precision medicine approaches.



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Novel method of extracting motion from natural movies

Publication date: Available online 9 August 2017
Source:Journal of Neuroscience Methods
Author(s): Wataru Suzuki, Noritaka Ichinohe, Toshiki Tani, Taku Hayami, Naohisa Miyakawa, Satoshi Watanabe, Hiroshige Takeichi
BackgroundThe visual system in primates can be segregated into motion and shape pathways. Interaction occurs at multiple stages along these pathways. Processing of shape-from-motion and biological motion is considered to be a higher-order integration process involving motion and shape information. However, relatively limited types of stimuli have been used in previous studies on these integration processes.New methodWe propose a new algorithm to extract object motion information from natural movies and to move random dots in accordance with the information. The object motion information is extracted by estimating the dynamics of local normal vectors of the image intensity projected onto the x-y plane of the movie.ResultsAn electrophysiological experiment on two adult common marmoset monkeys (Callithrix jacchus) showed that the natural and random dot movies generated with this new algorithm yielded comparable neural responses in the middle temporal visual area.Comparison with existing methodsIn principle, this algorithm provided random dot motion stimuli containing shape information for arbitrary natural movies. This new method is expected to expand the neurophysiological and psychophysical experimental protocols to elucidate the integration processing of motion and shape information in biological systems.ConclusionsThe novel algorithm proposed here was effective in extracting object motion information from natural movies and provided new motion stimuli to investigate higher-order motion information processing.



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Dissipation kinetics, pre-harvest residue limits, and hazard quotient assessments of pesticides flubendiamide and fluopicolide in Korean melon ( Cucumis melo L. var. makuwa ) grown under regulated conditions in plastic greenhouses

Abstract

The dissipation kinetics, pre-harvest residue limits, and hazard quotient (HQ) assessments of the pesticides flubendiamide and fluopicolide were conducted for Korean melon (Cucumis melo L. var. makuwa) cultivated at two different sites. A single extraction and cleanup procedure was carried out using acetone (partitioned with dichloromethane) and amino solid-phase extraction cartridges, respectively. Residue analysis was performed by HPLC with ultraviolet detection. Both pesticides showed excellent linearity with correlation coefficients of 0.9999 and 0.9996 for flubendiamide and fluopicolide, respectively. The accuracy (expressed as recovery %) at three spiking levels was 92.0–103.6 and 82.8–105.3%, and the precision (expressed as relative standard deviation) was 1.7–3.4 and 2.7–5.3% for flubendiamide and fluopicolide, respectively. The initial residues of flubendiamide/fluopicolide were 0.326/0.376 and 0.206/0.298 mg/kg at sites 1 and 2, respectively. These amounts were substantially lower than the maximum residue limits (MRLs = 1 and 0.5 mg/kg for flubendiamide and fluopicolide, respectively) established by the Korean Ministry of Food and Drug Safety. The half-lives of flubendiamide were 5.8 and 6.5 days, and those of fluopicolide were 6.7 and 9.1 days at sites 1 and 2, respectively. The shorter half-lives were attributed to seasonal variations (higher temperatures) and enzymatic and metabolic profiling. The risk assessment HQs of flubendiamide were 0.217/0.249 on day 0, which decreased to 0.102/0.168 on day 5, and to 0.065/0.88 on day 10; the HQ values for fluopicolide were 0.029/0.042, 0.022/0.025, and 0.010/0.019 on day 0, day 5, and day 10, for sites 1/2, respectively. From this data, we concluded that the fruits could be consumed safely.

http://ift.tt/2fv619w

Flexible biodegradable citrate-based polymeric step-index optical fiber

Publication date: October 2017
Source:Biomaterials, Volume 143
Author(s): Dingying Shan, Chenji Zhang, Surge Kalaba, Nikhil Mehta, Gloria B. Kim, Zhiwen Liu, Jian Yang
Implanting fiber optical waveguides into tissue or organs for light delivery and collection is among the most effective ways to overcome the issue of tissue turbidity, a long-standing obstacle for biomedical optical technologies. Here, we report a citrate-based material platform with engineerable opto-mechano-biological properties and demonstrate a new type of biodegradable, biocompatible, and low-loss step-index optical fiber for organ-scale light delivery and collection. By leveraging the rich designability and processibility of citrate-based biodegradable polymers, two exemplary biodegradable elastomers with a fine refractive index difference and yet matched mechanical properties and biodegradation profiles were developed. Furthermore, we developed a two-step fabrication method to fabricate flexible and low-loss (0.4 db/cm) optical fibers, and performed systematic characterizations to study optical, spectroscopic, mechanical, and biodegradable properties. In addition, we demonstrated the proof of concept of image transmission through the citrate-based polymeric optical fibers and conducted in vivo deep tissue light delivery and fluorescence sensing in a Sprague-Dawley (SD) rat, laying the groundwork for realizing future implantable devices for long-term implantation where deep-tissue light delivery, sensing and imaging are desired, such as cell, tissue, and scaffold imaging in regenerative medicine and in vivo optogenetic stimulation.



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PNIPAAm-co-Jeffamine® (PNJ) scaffolds as in vitro models for niche enrichment of glioblastoma stem-like cells

Publication date: October 2017
Source:Biomaterials, Volume 143
Author(s): John M. Heffernan, James B. McNamara, Sabine Borwege, Brent L. Vernon, Nader Sanai, Shwetal Mehta, Rachael W. Sirianni
Glioblastoma (GBM) is the most common adult primary brain tumor, and the 5-year survival rate is less than 5%. GBM malignancy is driven in part by a population of GBM stem-like cells (GSCs) that exhibit indefinite self-renewal capacity, multipotent differentiation, expression of neural stem cell markers, and resistance to conventional treatments. GSCs are enriched in specialized niche microenvironments that regulate stem phenotypes and support GSC radioresistance. Therefore, identifying GSC-niche interactions that regulate stem phenotypes may present a unique target for disrupting the maintenance and persistence of this treatment resistant population. In this work, we engineered 3D scaffolds from temperature responsive poly(N-isopropylacrylamide-co-Jeffamine M-1000^® acrylamide), or PNJ copolymers, as a platform for enriching stem-specific phenotypes in two molecularly distinct human patient-derived GSC cell lines. Notably, we observed that, compared to conventional neurosphere cultures, PNJ cultured GSCs maintained multipotency and exhibited enhanced self-renewal capacity. Concurrent increases in expression of proteins known to regulate self-renewal, invasion, and stem maintenance in GSCs (NESTIN, EGFR, CD44) suggest that PNJ scaffolds effectively enrich the GSC population. We further observed that PNJ cultured GSCs exhibited increased resistance to radiation treatment compared to GSCs cultured in standard neurosphere conditions. GSC radioresistance is supported in vivo by niche microenvironments, and this remains a significant barrier to effectively treating these highly tumorigenic cells. Taken in sum, these data indicate that the microenvironment created by synthetic PNJ scaffolds models niche enrichment of GSCs in patient-derived GBM cell lines, and presents tissue engineering opportunities for studying clinically important behaviors such as radioresistance in vitro.



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Astrocytes and endoplasmic reticulum stress: A bridge between obesity and neurodegenerative diseases

Publication date: Available online 10 August 2017
Source:Progress in Neurobiology
Author(s): Cynthia A. Martin-Jiménez, Ángela García-Vega, Ricardo Cabezas, Gjumrakch Aliev, Valentina Echeverria, Janneth González, George E. Barreto
Endoplasmic reticulum (ER) is a subcellular organelle involved in protein folding and processing. ER stress constitutes a cellular process characterized by accumulation of misfolded proteins, impaired lipid metabolism and induction of inflammatory responses. ER stress has been suggested to be involved in several human pathologies, including neurodegenerative diseases and obesity. Different studies have shown that both neurodegenerative diseases and obesity trigger similar cellular responses to ER stress. Moreover, both diseases are assessed in astrocytes as evidences suggest these cells as key regulators of brain homeostasis. However, the exact contributions to the effects of ER stress in astrocytes in the various neurodegenerative diseases and its relation with obesity are not well known. Here, we discuss recent advances in the understanding of molecular mechanisms that regulate ER stress-related disorders in astrocytes such as obesity and neurodegeneration. Moreover, we outline the correlation between the activated proteins of the unfolded protein response (UPR) in these pathological conditions in order to identify possible therapeutic targets for ER stress in astrocytes. We show that ER stress in astrocytes shares UPR activation pathways during both obesity and neurodegenerative diseases, demonstrating that UPR related proteins like ER chaperone GRP 78/Bip, PERK pathway and other exogenous molecules ameliorate UPR response and promote neuroprotection.



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Valproic Acid Sensitizes Breast Cancer Cells to Hydroxyurea through Inhibiting RPA2 Hyperphosphorylation-Mediated DNA Repair Pathway

Publication date: Available online 9 August 2017
Source:DNA Repair
Author(s): Youjia Tian, Guochao Liu, Hui Wang, Zhujun Tian, Zuchao Cai, Fengmei Zhang, Yue Luo, Shue Wang, Gongshe Guo, Xiaowei Wang, Simon Powell, Zhihui Feng
It was reported that valproic acid (VPA, a histone deacetylase inhibitor) can sensitize cancer cells to hydroxyurea (HU, a ribonucleotide reductase inhibitor) for chemotherapy, although the mechanism of VPA-induced HU sensitization is unclear. In this study, we systematically characterized VPA-induced HU sensitization of breast cancer cells. Multiple breast cancer cell models were employed to investigate whether the safe concentration of 0.5mM VPA and 2mM HU can result in DNA double-strand breaks (DSBs) and impact cell survival. Furthermore, the underlying mechanism was explored through cell biology assays, including clonogenic survival, homologous recombination (HR) activity, immunoblot and immunofluorescence. We found that VPA and HU cooperatively suppressed cancer cell survival. VPA resulted in the accumulation of more DNA double-strand breaks (DSBs) in response to HU-induced replication arrest and was able to block HU-stimulated homologous recombination (HR) through inhibiting the activity of two key HR repair proteins by hyperphosphorylation of replication protein A2 (RPA2-p) and recombinase Rad51. However, apoptosis was not detected under this condition. In addition, the results from the survival fraction in the cells expressing defective RPA2-p showed that VPA disrupted the HU-induced RPA2-p-Rad51-mediated HR pathway. Importantly, these findings were further supported by analyzing primary-culture cells from the tissue of chemical carcinogen (DMBA)-induced breast cancer in rats. Thus, our data demonstrated that VPA and HU synergistically suppressed tumor cells via disturbing RPA2-p-mediated DNA repair pathway, which provides a new way for combining chemotherapeutic drugs to sensitize breast cancer cells.



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Reflections on a Decade

Publication date: 9 August 2017
Source:Cell Host & Microbe, Volume 22, Issue 2

We invited ten Cell Host & Microbe authors, who are experts in their field, to join us in celebrating our anniversary by highlighting an area of host-microbe research that the journal has contributed to advancing.

Teaser

We invited ten Cell Host & Microbe authors, who are experts in their field, to join us in celebrating our anniversary by highlighting an area of host-microbe research that the journal has contributed to advancing.


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The Gut Microbiota, Food Science, and Human Nutrition: A Timely Marriage

Publication date: 9 August 2017
Source:Cell Host & Microbe, Volume 22, Issue 2
Author(s): Michael J. Barratt, Carlito Lebrilla, Howard-Yana Shapiro, Jeffrey I. Gordon
Analytic advances are enabling more precise definitions of the molecular composition of key food staples incorporated into contemporary diets and how the nutrient landscapes of these staples vary as a function of cultivar and food processing methods. This knowledge, combined with insights about the interrelationship between consumer microbiota configurations and biotransformation of food ingredients, should have a number of effects on agriculture, food production, and strategies for improving the nutritional value of foods and health status. These effects include decision-making about which cultivars of current or future food staples to incorporate into existing and future food systems, and which components of waste streams from current or future food manufacturing processes have nutritional value that is worth capturing. They can also guide which technologies should be applied, or need to be developed, to produce foods that support efficient microbial biotransformation of their ingredients into metabolic products that sustain health.

Teaser

In this Perspective, Barratt et al. propose the integration of preclinical models, food science technologies, and human studies to generate detailed knowledge of the biotransformation of food ingredients by consumers' gut microbiota. This could alter traditional definitions of nutrient content and inform global efforts designed to produce affordable, healthier foods.


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Establishing Causality: Opportunities of Synthetic Communities for Plant Microbiome Research

Publication date: 9 August 2017
Source:Cell Host & Microbe, Volume 22, Issue 2
Author(s): Julia A. Vorholt, Christine Vogel, Charlotte I. Carlström, Daniel B. Müller
Plant microbiome research highlights the importance of indigenous microbial communities for host phenotypes such as growth and health. It aims to discover the molecular basis by which host-microbe and microbe-microbe interactions shape and maintain microbial communities and to understand the role of individual microorganisms, as well as their collective ecosystem function. Here, we discuss reductionist approaches to disentangle the inherent complexity of interactions in situ. Experimentally tractable, synthetic communities enable testing of hypotheses by targeted manipulation in gnotobiotic systems. Modifications of microbial, host, and environmental parameters allow for the quantitative assessment of host and microbe characteristics with dynamic and spatial resolution. We summarize first insights from this emerging field and discuss current challenges and limitations. Using multifaceted approaches to detect interactions and functions will provide new insights into the fundamental biology of plant-microbe interactions and help to harness the power of the microbiome.

Teaser

Plant microbiome research highlights the importance of indigenous microbial communities for host phenotypes such as growth and health. It aims to discover the molecular basis by which host-microbe and microbe-microbe interactions shape and maintain microbial communities and to understand the role of individual microorganisms, as well as their collective ecosystem function. Here, we discuss reductionist approaches to disentangle the inherent complexity of interactions in situ. Experimentally tractable, synthetic communities enable testing of hypotheses by targeted manipulation in gnotobiotic systems. Modifications of microbial, host, and environmental parameters allow for the quantitative assessment of host and microbe characteristics with dynamic and spatial resolution. We summarize first insights from this emerging field and discuss current challenges and limitations. Using multifaceted approaches to detect interactions and functions will provide new insights into the fundamental biology of plant-microbe interactions and help to harness the power of the microbiome.


http://ift.tt/2uqZ9AE

Commensal Fungi in Health and Disease

Publication date: 9 August 2017
Source:Cell Host & Microbe, Volume 22, Issue 2
Author(s): Jose J. Limon, Joseph H. Skalski, David M. Underhill
Fungi are increasingly being recognized as common members of the microbiomes found on nearly all mucosal surfaces, and interest is growing in understanding how these organisms may contribute to health and disease. In this review, we investigate recent developments in our understanding of the fungal microbiota or "mycobiota" including challenges faced in characterizing it, where these organisms are found, their diversity, and how they interact with host immunity. Growing evidence indicates that, like the bacterial microbiota, the fungal microbiota is often altered in disease states, and increasingly studies are being designed to probe the functional consequences of such fungal dysbiosis on health and disease.

Teaser

Like bacteria, fungi are part of the microbiomes found on body surfaces, and interest is growing in how these organisms contribute to health and disease. Limon et al. review recent developments in identifying members of the fungal microbiota as well as understanding how our immune systems interact with commensal fungi.


http://ift.tt/2uIrm0O

Innate Immunity to Intracellular Pathogens: Balancing Microbial Elimination and Inflammation

Publication date: 9 August 2017
Source:Cell Host & Microbe, Volume 22, Issue 2
Author(s): Gabriel Mitchell, Ralph R. Isberg
Recent excitement regarding immune clearance of intracellular microorganisms has focused on two systems that maintain cellular homeostasis. One system includes cellular autophagy components that mediate degradation of pathogens in membrane-bound compartments, in a process termed xenophagy. The second system is driven by interferon-regulated GTPases that promote rupture of pathogen-containing vacuoles and microbial degradation. In the case of xenophagy, pathogen sequestration and compartmentalization suppress inflammation. In contrast, interferon-driven events can lead to exposure of pathogen-associated molecular patterns to the host cytosol with consequent inflammasome activation. Paradoxically, signals and factors involved in xenophagy also mobilize interferon-regulated GTPases, which drive the inflammatory response, indicating considerable cross-talk between these pathways. How these responses are prioritized remains to be understood. In this review, we describe mechanisms of intracellular pathogen clearance that rely on the autophagy machinery and interferon-regulated GTPases, and speculate how these pathways engage each other to balance pathogen elimination with inflammation.

Teaser

In their review, Mitchell and Isberg describe mechanisms of intracellular pathogen clearance that rely on the autophagy machinery and interferon-regulated GTPases and discuss how these pathways may be interacting with each other to balance pathogen elimination with inflammation.


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10 for 10!

Publication date: 9 August 2017
Source:Cell Host & Microbe, Volume 22, Issue 2
Author(s): Christine Cosma, Ella Hinson, Lakshmi Goyal




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Ten Strategies of Interferon Evasion by Viruses

Publication date: 9 August 2017
Source:Cell Host & Microbe, Volume 22, Issue 2
Author(s): Adolfo García-Sastre
Viruses infecting vertebrate hosts must overcome the interferon (IFN)-mediated antiviral response to replicate and propagate to new hosts. The complex regulation of the IFN response allows viruses to antagonize IFN at multiple levels. However, no single strategy appears to be the golden ticket, and viruses have adopted multiple means to dampen this host defense. This Review does not exhaustively cover all mechanisms of viral IFN antagonism. Rather it examines the ten most common strategies that viruses use to subvert the IFN response with examples from publications appearing in the last 10 years of Cell Host & Microbe. The virus-host interactions involved in induction and evasion of IFN represent a fertile area of research due to the significant large number of host and viral products that regulate this response, resulting in an intricate dance between hosts and their pathogens to achieve an optimal balance between virus replication, host disease, and survival.

Teaser

Viruses are formidable pathogens that take advantage of the infected cell machinery while disarming the antiviral host defenses. García-Sastre reviews the most common mechanisms used by viruses to antagonize the antiviral interferon response, illustrating the complexity of pathways that sense viral infection and regulate antiviral innate immune responses.


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Circadian Coordination of Antimicrobial Responses

Publication date: 9 August 2017
Source:Cell Host & Microbe, Volume 22, Issue 2
Author(s): Paola Tognini, Christoph A. Thaiss, Eran Elinav, Paolo Sassone-Corsi
Microbial infection poses a threat to organismal homeostasis and therefore must be efficiently counteracted by host defense mechanisms. It has been recently demonstrated that the immune system may anticipate an emerging pathogenic exposure through a heightened inflammatory state. Such anticipatory responses to fluctuating environmental conditions are typically orchestrated by the circadian clock, an intrinsic time-keeping system that adapts tissue physiology to diurnal variations in external influences. Here, we review current knowledge about the interplay between the circadian clock and antimicrobial responses. We summarize the molecular strategies employed by the circadian system against specific pathogens, the core-clock proteins as well as cells in which they are expressed that mediate host defense, and the consequences of circadian variations on immune function. Furthermore, we highlight the possible implications of such circadian gating in immune reactions against pathogenic infections for the chronopharmacology of antibacterial and antiviral therapies.

Teaser

Tognini et al. review evidence showing how the circadian clock regulates the immune response to multiple infectious agents in different tissues, and the importance of the daily control of immune system functions to maximize the host defense against a pathogenic attack.


http://ift.tt/2uItaqJ

Principles of Broad and Potent Antiviral Human Antibodies: Insights for Vaccine Design

Publication date: 9 August 2017
Source:Cell Host & Microbe, Volume 22, Issue 2
Author(s): James E. Crowe
Antibodies are the principal immune effectors that mediate protection against reinfection following viral infection or vaccination. Robust techniques for human mAb isolation have been developed in the last decade. The study of human mAbs isolated from subjects with prior immunity has become a mainstay for rational structure-based, next-generation vaccine development. The plethora of detailed molecular and genetic studies coupling the structure of antigen-antibody complexes with their antiviral function has begun to reveal common principles of critical interactions on which we can build better vaccines and therapeutic antibodies. This review outlines the approaches to isolating and studying human antiviral mAbs and discusses the common principles underlying the basis for their activity. This review also examines progress toward the goal of achieving a comprehensive understanding of the chemical and physical basis for molecular recognition of viral surface proteins in order to build predictive molecular models that can be used for vaccine design.

Teaser

Antibodies are the principal immune effectors that protect against viral reinfection. The review by Crowe outlines approaches to isolating and studying human antiviral monoclonal antibodies and details the common principles underlying the basis for their antiviral activity. Use of this understanding to build predictive models for vaccine design is discussed.


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Of Mice, Macaques, and Men: Broadly Neutralizing Antibody Immunotherapy for HIV-1

Publication date: 9 August 2017
Source:Cell Host & Microbe, Volume 22, Issue 2
Author(s): Yoshiaki Nishimura, Malcolm A. Martin
The neutralizing antibodies targeting the HIV-1 envelope protein have been a major focus for HIV therapy. Early studies with anti-HIV-1 neutralizing monoclonal antibodies (mAbs) administered to infected individuals showed some promise, as they resulted in transient reductions in plasma viremia in some recipients. However, resistant viral variants rapidly emerged. A major development during the past 6 to 7 years has been the isolation and characterization of highly potent and broadly neutralizing mAbs (bNAbs) from infected individuals known as "elite neutralizers." These "next-generation" bNAbs have been tested in animal model systems and shown to effectively control virus replication, particularly following combination immunotherapy. The success of these preclinical animal studies has led to human clinical trials using an individual bNAb for therapy. This review examines recent findings from animal models and human clinical trials and discusses the future use of bNAbs for HIV-1 treatment.

Teaser

Broadly neutralizing antibodies (bNAbs) can reduce HIV-1 levels to variable extents and time periods in animals inoculated with HIV and HIV-like viruses and, recently, in HIV-infected individuals. Nishimura and Martin review these recent findings in HIV immunotherapy and discuss the potential for combination bNAb treatment, using newly engineered derivatives, to exhibit improved potency.


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Salmonella SPI-2 Type III Secretion System Effectors: Molecular Mechanisms And Physiological Consequences

Publication date: 9 August 2017
Source:Cell Host & Microbe, Volume 22, Issue 2
Author(s): Elliott Jennings, Teresa L.M. Thurston, David W. Holden
Serovars of Salmonella enterica cause both gastrointestinal and systemic diseases in a broad range of mammalian hosts, including humans. Salmonella virulence depends in part on its pathogenicity island 2 type III secretion system (SPI-2 T3SS), which is required to translocate at least 28 effector proteins from vacuolar-resident bacteria into host cells. Comparative genomic analysis reveals that all serovars encode a subset of "core" effectors, suggesting that they are critical for virulence in different hosts. An additional subset of effectors is found sporadically throughout different serovars, and several inhibit activation of the innate immune system. In this Review, we summarize the biochemical activities, host cell interaction partners, and physiological functions of SPI-2 T3SS effectors in the context of the selective pressures encountered by S. enterica in vivo. We also consider some of the remaining challenges to achieve a unified understanding of how effector activities work together to promote Salmonella virulence.

Teaser

The Salmonella SPI-2 type III secretion system transfers a large number of effector proteins to host cells. In this Review, Holden and colleagues summarize the biochemical activities, host cell interaction partners, and physiological functions of these effectors in the context of the selective pressures encountered by S. enterica in vivo.


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The Molecular Basis of Erythrocyte Invasion by Malaria Parasites

Publication date: 9 August 2017
Source:Cell Host & Microbe, Volume 22, Issue 2
Author(s): Alan F. Cowman, Christopher J. Tonkin, Wai-Hong Tham, Manoj T. Duraisingh
Plasmodium species cause malaria by proliferating in human erythrocytes. Invasion of immunologically privileged erythrocytes provides a relatively protective niche as well as access to a rich source of nutrients. Plasmodium spp. target erythrocytes of different ages, but share a common mechanism of invasion. Specific engagement of erythrocyte receptors defines target cell tropism, activating downstream events and resulting in the physical penetration of the erythrocyte, powered by the parasite's actinomyosin-based motor. Here we review the latest in our understanding of the molecular composition of this highly complex and fascinating biological process.

Teaser

Malaria parasites invade erythrocytes, a host cell that provides a protective niche and rich source of nutrients. In this review, Cowman et al. examine this invasion process and the roles of multiple ligand-receptor interactions that define target cell tropism, and activate downstream events resulting in physical penetration of the erythrocyte.


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Inflammation, Antibiotics, and Diet as Environmental Stressors of the Gut Microbiome in Pediatric Crohn’s Disease

Publication date: 9 August 2017
Source:Cell Host & Microbe, Volume 22, Issue 2
Author(s): James D. Lewis, Eric Z. Chen, Robert N. Baldassano, Anthony R. Otley, Anne M. Griffiths, Dale Lee, Kyle Bittinger, Aubrey Bailey, Elliot S. Friedman, Christian Hoffmann, Lindsey Albenberg, Rohini Sinha, Charlene Compher, Erin Gilroy, Lisa Nessel, Amy Grant, Christel Chehoud, Hongzhe Li, Gary D. Wu, Frederic D. Bushman




http://ift.tt/2uIqTvK

Diversity of Functionally Permissive Sequences in the Receptor-Binding Site of Influenza Hemagglutinin

Publication date: 9 August 2017
Source:Cell Host & Microbe, Volume 22, Issue 2
Author(s): Nicholas C. Wu, Jia Xie, Tianqing Zheng, Corwin M. Nycholat, Geramie Grande, James C. Paulson, Richard A. Lerner, Ian A. Wilson




http://ift.tt/2uqKsxt

Interlaminar strengthening of multidirectional laminates using polymer additive manufacturing

Publication date: 5 November 2017
Source:Materials & Design, Volume 133
Author(s): M.S. Islam, P. Prabhakar
A novel approach for improving the interlaminar shear strength (ILSS) properties of multi-directional prepreg laminates using polymer additive manufacturing (PAM) technology is proposed in this paper. Fused deposition modeling (FDM) is the PAM technology used for imparting patterns onto carbon prepregs. These modified prepregs are further used for fabricating multi-directional laminates. Prior to manufacturing the laminates, interlaminar regions that are most susceptible to delamination type failure are identified using numerical simulations for selectively reinforcing these critical regions. Next, the influence of printed reinforcements on the ILSS of modified laminates is compared against pristine laminates by conducting short beam shear (SBS) tests. Significant improvement in the ILSS values of up to 28% is observed, which can be attributed to the resistance offered by the printed reinforcements that steered the delamination surfaces along undulated paths as opposed to smooth or straight paths in pristine laminates. Such behavior corroborates the resistance to delamination offered by these printed reinforcements. In summary, this is a pioneering study for exploring the feasibility of using PAM technology for imparting reinforcements at the interlaminar regions in multi-directional laminates with the intention of minimizing delamination.

Graphical abstract

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Control of the cell structure of microcellular silicone rubber/nanographite foam for enhanced mechanical performance

Publication date: 5 November 2017
Source:Materials & Design, Volume 133
Author(s): Jianwei Bai, Xia Liao, Erbo Huang, Yong Luo, Qi Yang, Guangxian Li
Microcellular silicone rubber/nanographite foam with the smallest cell diameter and the largest cell density compared to the previous studies was prepared using supercritical carbon dioxide as an environmentally benign foaming agent in this study. Both the cell microstructure and properties of porous composite were investigated in detail. In silicone rubber/nanographite system, the incorporation of nanographite into silicone rubber significantly induced heterogeneous bubble nucleation and enhanced the matrix strength, which resulted in the decreased average cell diameter from 4.97 to 1.12μm and the increased cell density from 8.87×10⁸cells/cm³ to 1.25×10¹⁰cells/cm³. The microcellular rubber foam with decreased cell size, increased cell density and narrow cell distribution was corresponded to the excellent compressive strength and higher hardness, which reduced the content of silica. Furthermore, the thermal decomposition temperature of the obtained foam increased from 380°C to 413°C due to the introduction of nanographite. The silicone rubber/nanographite foam with improved performance possessed potential in wide applications.

Graphical abstract

http://ift.tt/2vGrBOC

Self-organizing silver and ultrasmall iron oxide nanoparticles prepared with ginger rhizome extract: Characterization, biomedical potential and microstructure analysis of hydrocolloids

Publication date: 5 November 2017
Source:Materials & Design, Volume 133
Author(s): Olena Ivashchenko, Jacek Gapiński, Barbara Peplińska, Łucja Przysiecka, Tomasz Zalewski, Grzegorz Nowaczyk, Marcin Jarek, Anna Marcinkowska-Gapińska, Stefan Jurga
Multimodal nanoparticles (NPs) that may be used for therapies and diagnostics is the most promising trend for efficient therapy. We demonstrate that nanocomposite based on self-organizing silver and ultrasmall magnetic iron oxide NPs (MAg) produced in one-step synthesis revealed unique combination of fluorescence, bactericidal, fungicidal properties and have a potential as magnetic resonance imaging (MRI) contrast agent. Using the green chemistry approach, ginger (Zingiber officinale) rhizome extract was applied as capping agent for MAg synthesis, providing also additional fluorescent properties of NPs and inducing hydrocolloids structuring. The MAg were investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive microanalysis (EDS), fluorescence microscopy, cryo-SEM, dynamic light scattering (DLS) techniques, Fourier transform infrared (FTIR) and ultraviolet–visible (UV–Vis) spectroscopies. MAg dispersions in water and some biological media are very stable which is important for biomedical application. The existence of microstructure in MAg hydrocolloids was proved. The hierarchical character and high ordering of this microstructure were discovered and its level-by-level building blocks were investigated. The microstructure was found to be responsible for fluorescence emittance of MAg hydrocolloids. The properties as well as potential application of the MAg hydrocolloids is yet to be discovered.

Graphical abstract

http://ift.tt/2vGMrgR

Fatigue behavior of a Fe-Mn-Si shape memory alloy used for prestressed strengthening

Publication date: 5 November 2017
Source:Materials & Design, Volume 133
Author(s): E. Ghafoori, E. Hosseini, C. Leinenbach, J. Michels, M. Motavalli
Cyclic deformation and fatigue behavior of an iron-based shape memory alloy (Fe-SMA) Fe-17Mn-5Si-10Cr-4Ni-1(V,C) were studied. In the first step, cyclic tensile tests were performed to characterize the material's mechanical properties in tension (elongation at break, yield, and tensile strength) as well as the recovery behavior of the alloy. Furthermore, the effect of strain rate on the cyclic loading tests was investigated. It was observed that the strain rate has a clear influence on the stress-strain behavior of the alloy. In the second step, the fatigue behavior of the alloy after pre-straining and thermal activation under strain-controlled conditions was evaluated. While the stiffness of the alloy remained almost constant during high-cycle fatigue loading, a decrease in the recovery stress was observed, which should be taken into account in design assessments. The loss in the recovery stress was assumed to be mainly a result of a transformation-induced relaxation (TIR) under cyclic loading. Furthermore, this study examines the applicability of a constant life diagram (CLD) model to determine the fatigue limit of the alloy for different stress ratios (R). The existing results of the fatigue tests showed full consistency with the proposed fatigue design criterion. A formulation based on the CLD model was proposed for a safe design of the alloy as a structural pre-stressing element under a high-cycle fatigue loading regime.

Graphical abstract

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Cold gas dynamic spray additive manufacturing today: Deposit possibilities, technological solutions and viable applications

Publication date: 5 November 2017
Source:Materials & Design, Volume 133
Author(s): R.N. Raoelison, Ch. Verdy, H. Liao
This paper reports the current potentials of cold gas dynamic spraying (CGDS). CGDS has been significantly developed to produce several functional solutions categorized as follows: deposits with a single powder nature, composites-based deposits, nanotechnological deposits and hybrid coating/substrate assemblies. CGDS process has improved in proficiency and is still gaining attention from scientists and industry. Covering a wide range of materials, both standard and advanced, this additive manufacturing process offers substantial applications for surface functionalization, structural or dimensional restoration, bulk production providing specific material properties, and art/decoration. Progress in terms of material processing capabilities and applications are ongoing. CGDS brings opportunities of better materials and innovative solutions. This review also indicates some recent challenges of cold spraying. Those represent future research directions to increase the enactment of CGDS as a proven viable innovative additive manufacturing method.

Graphical abstract

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Microstructure, mechanical and thermionic emission properties of a directionally solidified LaB6-VB2 eutectic composite

Publication date: 5 November 2017
Source:Materials & Design, Volume 133
Author(s): Xinyu Yang, Pan Wang, Zhenghong Wang, Ke Hu, Hefa Cheng, Zhi Li, Jiuxing Zhang
The directionally solidified (DS) LaB6-VB2 eutectic composite is successfully prepared by the optical floating zone technique. The effect of solidification rate on the microstructure characteristic, mechanical and thermionic properties are investigated. DS LaB6-VB2 eutectic composite presents a mixed rod and lamellar microstructures as the solidification rate is increased from 8.3 to 55.6μm/s, and the formation of rod structure is ascribed to the necking of unstable lamellar. The fracture toughness in transverse section is higher than that in longitudinal section at the same rate, and the highest fracture toughness of 7.23MPa·m^1/2 in transverse section and 6.47MPa·m^1/2 in longitudinal section are obtained at V=27.8μm/s. Thermionic emission of DS LaB6-VB2 eutectic composite obeys the Longo theory, and the optimal current density of 51.92A·cm⁻² is measured at 1873K.

Graphical abstract

http://ift.tt/2vGI05R

Combining stereolithography and replica molding: On the way to superhydrophobic polymeric devices for photovoltaics

Publication date: 5 November 2017
Source:Materials & Design, Volume 133
Author(s): Caterina Credi, Diego Pintossi, Claudia L. Bianchi, Marinella Levi, Gianmarco Griffini, Stefano Turri
A strategy combining stereolithography (SL) and soft-lithography for the straightforward fabrication of superhydrophobic bulk devices is reported. Microtextured masters are rapidly prototyped by SL and passivated with a perfluorosilane. Such surface treatment enables the faultless fabrication of negative microstructured polydimethylsiloxane molds ultimately utilized to obtain bulk polymeric micropatterned structures by replica molding. As illustrative proof of concept, this approach is employed in the field of photovoltaics to realize the first example of superhydrophobic luminescent solar concentrators (LSCs) showing superior self-cleaning properties. Following our strategy, a new dye-doped acrylate mixture is developed and optimized to ensure complete wetting of the hollow microstructures present on the mold. By judiciously tailoring the photoinitiator concentration and by implementing a tailored double-step UV-irradiation process, complete UV-photopolymerization is achieved despite the significant thickness of the target samples. The high fidelity replication of the original SL-printed features on the daughter replicas as well as their super water-repellency are successfully demonstrated. The performance of the resulting superhydrophobic LSCs is investigated at varying device dimensions and found to be comparable with state-of-the-art systems. This study demonstrates the potential of high-resolution SL-printing in combination with replication techniques as a versatile tool to reproducibly fabricate microstructured superhydrophobic polymeric bulk devices in a straightforward fashion.

Graphical abstract

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Understanding and quantification of grain growth mechanism in ZrO2‑carbon nanotube composites

Publication date: 5 November 2017
Source:Materials & Design, Volume 133
Author(s): Ben Milsom, Harshit Porwal, Giuseppe Viola, Zhipeng Gao, Micheal J. Reece
The high temperature grain growth behaviour of Y2O3 partially stabilised ZrO2 and ZrO2-CNT (0.5 and 2vol%) composites was investigated in a series of isothermal experiments carried out between 1500 and 1800°C. The grain growth activation energy was found to be 417±20kJmol⁻¹ for the ZrO2, which increased with the addition of CNTs to 509±41 and 497±17 kJ mol⁻¹ for the 0.5 and 2vol% composites respectively. A sintering exponent of 2 was observed for the ZrO2, corresponding to normal grain growth, whilst the nanocomposites showed a CNT drag dominated sintering mechanism, with exponents of 2.7 and 3.2 for the 0.5 and 2vol% composites respectively. This work confirms and quantifies the direct influence of CNTs on the grain growth mechanism and activation energy of ZrO2-CNT composites.

Graphical abstract

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Experimental and numerical study on honeycomb sandwich panels under bending and in-panel compression

Publication date: 5 November 2017
Source:Materials & Design, Volume 133
Author(s): Guangyong Sun, Xintao Huo, Dongdong Chen, Qing Li
Sandwich structures have been extensively employed as lightweight composite components in aerospace and shipbuilding engineering for their high capacity of stiffness, strength and energy absorption. To explore the crushing behaviors of honeycomb sandwiches, both three-point bending (TPB) and in-panel compression (IPC) tests were performed on aluminum honeycomb sandwich panels in this study. The effects of several key structural parameters on crashworthiness characteristics and collapse mechanism were first explored through the experiments here. The experimental results divulged that crashworthiness and collapse mode of sandwich structures were greatly influenced by the structural parameters under the TPB test. The crash behaviors can be also affected by both structural and adhesive parameters in the IPC test. Through validating with the experimental data, the numerical models were established to capture some deformation and failure details in the crushing processes. Taking into account the adhesive interface in the finite element (FE) model, glue debonding was simulated for the IPC loading, which is in good agreement with the experimental results at the skin panel buckling. Based on the experimental results, theoretical solutions for the TPB test were also established to predict the peak load, energy absorption and collapse mode. This study provided a new basis for the further studies on the crashworthiness optimization of sandwich structures.

Graphical abstract

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TEMPO-oxidized cellulose nanofibers as interfacial strengthener in continuous-fiber reinforced polymer composites

Publication date: 5 November 2017
Source:Materials & Design, Volume 133
Author(s): B.E.B. Uribe, E.M.S. Chiromito, A.J.F. Carvalho, R. Arenal, J.R. Tarpani
This paper presents a fast and practical route to improve the stress transfer of continuous fiber-reinforced polymer matrix composite laminates. This method concerns on-the-surface treatment of unsized carbon and glass fiber fabrics with 2,2,6,6-TetraMethyl-1-PiperidinylOxy (TEMPO) oxidized cellulose nanofibers before the laminate manufacturing step. The proposed method generated an increase in ultimate flexural strength of 62% and 54% for carbon and glass fiber-reinforced epoxy, respectively, and enhanced the out-of-plane properties of both hierarchical systems, as proved by short beam strength test, which showed an improvement of approximately 40% for both. The nanocellulose interphase was measured via transmission electron microscopy and energy-dispersive X-ray spectroscopy (EDS) techniques, showing a thickness of approximately 20 nm for the hierarchical carbon fiber composite laminate.Taking into account these results, this method demonstrates to be a useful alternative in the design and manufacturing of modern hierarchical composite structures.

Graphical abstract

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Self nitrogen-doped carbon nanotubes as anode materials for high capacity and cycling stability lithium-ion batteries

Publication date: 5 November 2017
Source:Materials & Design, Volume 133
Author(s): Jiangang Li, Feng Zhang, Chundong Wang, Changzhen Shao, Baozong Li, Yi Li, Qi-Hui Wu, Yonggang Yang
The great demand for high-power lithium-ion batteries has spurred extensive research on carbonaceous electrode materials. Herein, we reported a facile way of preparing novel carbon nanotubes with high nitrogen doping. Helical and straight 3-aminophenol formaldehyde resin nanotubes were first prepared based on the self-assembly of the chiral amphiphiles, which were then used as carbon sources to fabricate self nitrogen-doped carbon nanotubes via pyrolysis process. When the resins were carbonized at 600°C, carbon nanotubes with a high nitrogen-content of 9.6wt% were obtained, which maintained the original morphology of the resins. The electrochemical tests disclosed that the carbon nanotubes exhibited excellent Li storage capacity and superior cycling stability. A high reversible specific capacity of 1056mAhg⁻¹ at 0.1Ag⁻¹ was obtained after 300cycles, which is greatly higher than that of graphite and most of polymer derived carbonaceous materials. The research data implied that the nitrogen doping content plays an important role in the electrochemical performance of the carbon nanotubes.

Graphical abstract

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Mechanical properties of explosively welded AA2519-AA1050-Ti6Al4V layered material at ambient and cryogenic conditions

Publication date: 5 November 2017
Source:Materials & Design, Volume 133
Author(s): Dariusz Boroński, Maciej Kotyk, Paweł Maćkowiak, Lucjan Śnieżek
This study presents the results of the mechanical properties of explosively welded AA2519-AA1050-Ti6Al4V layered material tested at ambient temperature and in cryogenic conditions. The possibility of modeling its mechanical properties based on the base material properties was additionally verified. Fractures of base materials and layered material specimens were also analyzed in order to determine the failure mechanisms in both temperature conditions. The results confirmed that the strength of aluminum alloys and titanium alloys improved with a decrease in temperature. The same effect was achieved for the layered material.It has been proved in this study that it is possible to model the layered material yield stress and ultimate tensile strength based on the analysis of its base material properties with some percent error. A much more problematic issue is to predict the elastic properties of the layered material described, e.g., by tensile elasticity modulus. The stiffness of the layered material depends on the load level and varies after aluminum alloy plastification. An influence of the mutual interaction of the explosively welded layers on Poisson's ratio was also observed.

Graphical abstract

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Probing InGaN immiscibility at AlGaN/InGaN heterointerface on silicon (111) through two-step capacitance-voltage and conductance-voltage profiles

Publication date: 5 November 2017
Source:Materials & Design, Volume 133
Author(s): Ankush Bag, Shubhankar Majumdar, Subhashis Das, Dhrubes Biswas
Immiscibility of InGaN hinders epitaxial growth of high-quality AlGaN/InGaN heterojunction, which could have superior performances than AlGaN/GaN in view of high-speed devices. AlGaN/InGaN/GaN double heterostructures have been grown on silicon (111) substrate using plasma assisted molecular beam epitaxy. All growth conditions for each sample have been kept identical except the InGaN channel thickness. Alloy inhomogeneity has been found to occur in the InGaN channel by high resolution (HR) X-ray diffractometer (XRD) and cross-sectional HR- transmission electron microscopy (TEM). This non-uniformity of alloy causes reduced indium incorporation with a decrease of channel thickness along with a thin InN binary alloy. Capacitance-voltage (C-V) profile has revealed non-uniformity of alloy and spatial position of InN in the channel due to variation of band-offset and carrier confinement. Unconventional two-step profile has been obtained for the heterostructure. Higher capacitance at near zero bias corroborates the formation of InN at AlGaN/InGaN due to larger band offset. Conductance-voltage (G-V) profiles further validate mapping of InGaN phase separation in terms of carrier trapping. Lower effect of trapping has been identified due to low bandgap InN formation at the interface. Effect of epilayer relaxation on the phase separation has also been discussed in terms of threading dislocation and V-defects.

Graphical abstract

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In vitro wear, corrosion and biocompatibility of electron beam melted γ-TiAl

Publication date: 5 November 2017
Source:Materials & Design, Volume 133
Author(s): Ashfaq Mohammad, Abdulrahman M. Al-Ahmari, Vamsi Krishna Balla, Mitun Das, Susmit Datta, Devinder Yadav, G.D. Janaki Ram
Electron beam melting (EBM), a powder bed fusion based additive manufacturing process, has been used to fabricate Ti-48Al-2Cr-2Nb γ-TiAl samples. The samples were evaluated for their potential use in biomedical applications in terms of in vitro wear, corrosion and biocompatibility in as-deposited (AD) and hot isostatically pressed (HIPed) conditions. The samples were found to exhibit a lamellar microstructure consisting of γ-TiAl and Ti3Al (α2) phases in both the conditions. However, their in vitro wear and corrosion performance in Hank's balanced salt solution (HBSS), with and without fetal bovine serum (FBS), was found to be very different. The AD samples exhibited comparable passive behavior to commercially pure titanium (CP-Ti). Their corrosion potentials and currents were better than those of CP-Ti. The γ-TiAl samples exhibited wear rates of the order of 10⁻⁴mm³/N·m in HBSS. The presence of FBS was found to increase the corrosion and the wear rate of this alloy increased by 65%. In vitro cell culture experiments, using NIH3T3 cells, demonstrated that the EBM processed γ-TiAl is non-toxic and can allow cell adhesion and proliferation as effectively as CP-Ti.

Graphical abstract

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Fabrication of multiple-layered gradient cellular metal scaffold via electron beam melting for segmental bone reconstruction

Publication date: 5 November 2017
Source:Materials & Design, Volume 133
Author(s): Maria A. Surmeneva, Roman A. Surmenev, Ekaterina A. Chudinova, Andrei Koptioug, Mikhail S. Tkachev, Svetlana N. Gorodzha, Lars-Erik Rännar
The triple- and double-layered mesh Ti-based alloy scaffolds were successfully fabricated using electron beam melting (EBM). In this study Ti-based alloy cylindrical scaffolds with different 3D architectures intended for the segmental bone defect treatment were systematically compared. All lattice-like scaffolds were additively manufactured using EBM technology from Ti6Al4V to mimic the structures of human trabecular bone. Cylindrically-shaped lattice scaffolds (outer diameter of 15mm and length of 35mm) of five different types were designed and manufactured. Four types were tubular with inner hole diameter of 5mm and two lattice layers of different density. Fifth type was cylindrical with three lattice layers of different density. In all samples outer lattice layer was most dense, and inner layers- least dense. Mechanical properties of scaffolds were determined by conducting uniaxial compression testing. The strain-stress curves for all samples with gradient porosities showed considerable ductility.

Graphical abstract

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Effect of scan pattern on the microstructure and mechanical properties of Powder Bed Fusion additive manufactured 17-4 stainless steel

Publication date: 5 November 2017
Source:Materials & Design, Volume 133
Author(s): Andelle Kudzal, Brandon McWilliams, Clara Hofmeister, Frank Kellogg, Jian Yu, Joshua Taggart-Scarff, Jianyu Liang
Additive manufacturing (AM) of metallic parts is generating significant interest due to the ability to produce complex parts in a short period of time with minimal finishing required. However, the effect of laser scan strategy on the properties of finished parts is not well understood. In this paper the effects of laser scan line strategy on the microstructure and mechanical properties of stainless steel produced using metal Powder Bed Fusion (PBF) AM were characterized. Microstructure and phase identification were measured using X-ray diffraction and quantitative optical microscopy which found that all samples had a dual phase austenite-ferrite composition. Shorter scan lines perpendicular to the load direction resulted in 25% retained austenite, while elongated scan lines parallel to the load direction more than doubled the amount of austenite retained. A change of direction within the scan line path resulted in increased delamination porosity along the melt pool boundary and changes in volume fraction of retained austenite. Fractography, revealed cracks that propagated along melt pool boundaries. Understanding the effect of strategy on the microstructure and mechanical properties allows the producer of AM parts to implement materials by design strategies.

Graphical abstract

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Analysis of the 3D microstructure of tape-cast open-porous materials via a combination of experiments and modeling

Publication date: 5 November 2017
Source:Materials & Design, Volume 133
Author(s): S. Haj Ibrahim, M. Neumann, F. Klingner, V. Schmidt, T. Wejrzanowski
In the present paper, fabrication, characterization and modeling techniques are combined to analyze the microstructure of tape-cast open-porous materials. This kind of material is highly permeable to gases and at the same time has a high catalytic reactivity which leads to successful applications e.g. in high-temperature fuel cells. However, the microstructure of such material is complex and not fully understood. The main goal of this paper is to provide a realistic model of tape-cast porous microstructures based on the simulation of their fabrication process. In order to accomplish this, four different samples are fabricated by firing the green tapes obtained by the tape casting process. The microstructure of each sample is analyzed by means of micro-tomographic image data. Furthermore, a method for modeling open-porous 3D microstructures is proposed, where the cast slurry is represented by a system of spheres with a given volume fraction and radius distribution. Model-based post-processing of the simulated microstructures is proposed to improve the fit of the surface area. Finally, model validation is performed by means of a detailed statistical analysis of experimentally produced and virtual microstructures.

Graphical abstract

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Modeling and coupling effect evaluation of thermal conductivity of ternary opacifier/fiber/aerogel composites for super-thermal insulation

Publication date: 5 November 2017
Source:Materials & Design, Volume 133
Author(s): Jianming Yang, Huijun Wu, Gongsheng Huang, Yuying Liang, Yundan Liao
Nano-porous silica aerogel material exhibits extensive application prospects in aerospace, industry and buildings for excellent thermal insulation and energy efficiency owing to its ultra-low thermal conductivity. To further improve the high-temperature thermal insulation and mechanical property of aerogels, infrared opacifiers and reinforcing fibers are added into the aerogel matrix to form ternary opacifier/fiber/aerogel composites. In this study a theoretical model of predicting thermal conductivity of the ternary opacifier/fiber/aerogel composite is presented and validated with experimental results. Based on the model the effects of ternary opacifier/fiber/aerogel contents on the thermal conductivity are investigated by using a seven-batch ternary factorial design. A super-thermal insulation of 0.0185W·m⁻¹·K⁻¹ is achieved when the ternary opacifier/fiber/aerogel contents are 10wt%, 5wt% and 85wt% respectively. The coupling effect of the ternary opacifier/fiber/aerogel contents on the thermal conductivity of the composites is then explored to decrease the coupling thermal conductivity and improve the thermal insulating performance of the ternary aerogel composites. The results indicate that the coupling thermal conductivity can be decreased by enlarging the difference between the fiber and opacifier contents. This study could be used in the design of ternary opacifier/fiber/aerogel composites for improving their super-thermal insulation.

Graphical abstract

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Hemispherical nosed steel projectile high-speed penetration into aluminum target

Publication date: 5 November 2017
Source:Materials & Design, Volume 133
Author(s): Y.K. Xiao, H. Wu, Q. Fang, W. Zhang, X.Z. Kong
Terminal ballistic performance of high-strength projectiles penetrating into metallic targets is mostly concerned by both weapon and armor designers. Most existing works are concentrated on the rigid-eroding penetration regime, and limited studies have addressed the rigid-deforming-eroding penetration regime. In this paper, nineteen shots of hemispherical nosed D6A steel projectiles penetration test on 5A06-H112 aluminum targets is conducted with a wide range of velocities (696m/s–1870m/s). The non-monotonic dependence of depth of penetration (DOP) on the impact velocity is observed, which successively corresponds to the three penetration stages, i.e., rigid projectile penetration, deforming projectile penetration without eroding and eroding projectile penetration. Then, for the non-monotonic rigid-deforming-eroding projectile penetration regime, the applicability of the existing six classical theoretical models for both rigid and eroding projectile penetrations is evaluated. Furthermore, the transition velocities (the upper limit of rigid penetration and the lower limit of eroding penetration) are discussed and an empirical judgement criterion for the occurrence of non-monotonic dependence is proposed. Finally, by conducting the dynamic compression test, quasi-static tension test under varying temperature, etc., the Johnson-Cook model parameters for the present target and projectile are calibrated and validated by numerically simulating the present test.

Graphical abstract

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Contact-induced deformation and damage of rocks used in pavement materials

Publication date: 5 November 2017
Source:Materials & Design, Volume 133
Author(s): Carlos Celma Cervera, Denis Jelagin, Manfred N. Partl, Per-Lennart Larsson
Performance of stone-based construction materials, such as asphalt and unbound aggregate mixtures is defined to a great extent by the mechanics of the stone-to-stone interactions. Accordingly, the Discrete Element Method (DEM) is gaining popularity as a modelling tool to investigate the mechanical behavior of these materials. Contact and failure laws defining particles force-displacement relationships and the propensity of particles to break are crucial inputs for the DEM simulations. The present study aims at providing an experimental contact mechanics basis for the development of physically based stone-to-stone interaction laws. The attention is focused on investigating stone's force-displacement relationship and damage characteristics at pure normal loading for two stone materials used by the road industry. Experiments are performed at spherical contact profiles for cyclic and monotonically increasing loads. The emphasis lies on the evolution of contact compliance and accumulation of contact induced damage. The effect of surface roughness on the materials response is examined through comparative experiments performed on the specimens with different roughness values. Optical and environmental scanning electron microscopy (ESEM) observations of the contact induced damage at the material surface are presented and discussed in the context of contact mechanics. The implications of the reported experimental findings on the development of mechanics based contact and failure laws for the DEM modelling of stone-based construction materials are discussed.

Graphical abstract

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Cue-Dependent Inhibition in Posttraumatic Stress Disorder and Attention-Deficit/Hyperactivity Disorder

Publication date: Available online 9 August 2017
Source:Journal of Anxiety Disorders
Author(s): Zachary W. Adams, Michael Meinzer, Howard Mandel, Joshua Voltin, Blaine Caughron, Floyd R. Sallee, Mark Hamner, Zhewu Wang
ObjectiveAttention-deficit/hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD) are common among military veterans, but the comorbidity of these two psychiatric disorders remains largely unstudied. Evaluating response inhibition and cue-dependent learning as behavioral and neurocognitive mechanisms underlying ADHD/PTSD can inform etiological models and development of tailored interventions.MethodA cued go/no-go task evaluated response inhibition in 160 adult males. Participants were recruited from the community and a Veterans Administration medical center. Four diagnostic groups were identified: ADHD-only, PTSD-only, ADHD+PTSD, controls.ResultsGroup differences were observed across most indices of inhibitory functioning, reaction time, and reaction time variability, whereby PTSD-only and ADHD+PTSD participants demonstrated deficits relative to controls. No cue dependency effects were observed.ConclusionFinding complement prior work on neurocognitive mechanisms underlying ADHD, PTSD, and ADHD+PTSD. Lack of expected group differences for the ADHD-only group may be due to limited power. Additional work is needed to better characterize distinctions among clinical groups, as well as to test effects among women and youth.



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Cross-sectional and longitudinal associations between different exercise types and food cravings in free-living healthy young adults

Publication date: 1 November 2017
Source:Appetite, Volume 118
Author(s): Clemens Drenowatz, Line H. Evensen, Linda Ernstsen, John E. Blundell, Gregory A. Hand, Robin P. Shook, James R. Hébert, Stephanie Burgess, Steven N. Blair
IntroductionAn increase in energy intake due to alterations in hedonic appetite sensations may, at least in part, contribute to lower-than-expected weight loss in exercise interventions. The aim of this study was to examine cross-sectional and longitudinal associations between habitual exercise participation and food cravings in free-living young adults.MethodsA total of 417 adults (49% male, 28 ± 4 years) reported frequency and duration of walking, aerobic exercise, resistance exercise and other exercise at baseline and every 3 months over a 12-month period. Food cravings were assessed via the Control of Eating Questionnaire at baseline and 12-month follow-up.ResultsCross-sectional analyses revealed more frequent cravings for chocolate and a greater difficulty to resist food cravings in women compared to men (p < 0.01). Only with resistance exercise significant sex by exercise interaction effects were observed with favorable responses in men but not in women. Significant main effects were shown for walking and aerobic exercise with exercisers reporting more frequent food cravings for chocolate and fruits and greater difficulty to resist eating compared to non-exercisers (p < 0.05). Longitudinal analyses revealed significant interaction effects for other exercise (p < 0.05) with favorable results in men but not women. Furthermore, significant main effects were observed for aerobic exercise, resistance exercise and total exercise with an increase in exercise being associated with a reduced difficulty to resist food cravings (p < 0.05).DiscussionThe association between exercise participation and hedonic appetite sensations varies by exercise type and sex. Even though exercise was associated with more frequent and greater difficulty to food cravings in the cross-sectional analyses, which may be attributed to greater energy demands, longitudinal results indicate beneficial effects of increased exercise on appetite control, particularly in men.



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A small molecule activator of SIRT3 promotes deacetylation and activation of manganese superoxide dismutase

Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Jiaqi Lu, Hua Zhang, Xian Chen, Yong Zou, Jiasong Li, Li Wang, Minhao Wu, Jianye Zang, Yang Yu, Wei Zhuang, Qing Xia, Jiangyun Wang
The modulation of protein acetylation network is a promising strategy for life span extension and disease treatment (Sabari et al., 2016; Giblin et al., 2014) [1,2]. A variety of small molecules have been developed to target deacetylases, but extremely few of these molecules are capable of activating the mitochondrial NAD-dependent deacetylase sirtuin-3 (SIRT3) (Gertz and Steegborn, 2016; Scholz et al., 2015) [3,4]. Manganese superoxide dismutase (MnSOD) is the major superoxide scavenger in mitochondria, whose activity is regulated by SIRT3-mediated deacetylation, particularly at the Lys68 site (Chen et al., 2011) [5]. To investigate the influence of Lys68 acetylation on MnSOD activity, we produced a mutant MnSOD protein-bearing N-acetyllysine (AcK) at its Lys68 position through the genetic code expansion approach. We solved the crystal structure of this acetylated MnSOD (MnSODK68AcK), thus revealing the structural and electrostatic basis for the significant activity decrease upon Lys68 acetylation. On the basis of an assay we developed for the SIRT3-mediated deacetylation of MnSODK68AcK, we identified a novel SIRT3 activator, 7-hydroxy-3-(4′-methoxyphenyl) coumarin (C12), which binds to SIRT3 with high affinity and can promote the deacetylation and activation of MnSOD. C12 adds to the current repertoire of extremely few SIRT3 activators, which are potentially valuable for treating a wide array of diseases via modulating the cellular acetylome.

Graphical abstract

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Fructose induced neurogenic hypertension mediated by overactivation of p38 MAPK to impair insulin signaling transduction caused central insulin resistance

Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Pei-Wen Cheng, Yu-Te Lin, Wen-Yu Ho, Pei-Jung Lu, Hsin-Hung Chen, Chi-Cheng Lai, Gwo-Ching Sun, Tung-Chen Yeh, Michael Hsiao, Ching-Jiunn Tseng, Chun-Peng Liu
Type 2 diabetes are at a high risk of complications related to hypertension, and reports have indicated that insulin levels may be associated with blood pressure (BP). Fructose intake has recently been reported to promote insulin resistance and superoxide formation. The aim of this study is to investigate whether fructose intake can enhance superoxide generation and impair insulin signaling in the NTS and subsequently elevate BP in rats with fructose-induced hypertension. Treatment with fructose for 4 weeks increased the BP, serum fasting insulin, glucose, homeostatic model assessment-insulin resistance, and triglyceride levels and reduced the serum direct high-density lipoprotein level in the fructose group. The Tempol treatment recovered the fructose-induced decrease in nitric oxide production in the NTS. Immunoblotting and immunofluorescence analyses further showed that fructose increased the p38- and fructose-induced phosphorylation of insulin receptor substrate 1 (IRS1^S307) and suppressed Akt^S473 and neuronal nitric oxide synthase phosphorylation. Similarly, fructose was able to impair insulin sensitivity and increase insulin levels in the NTS. Fructose intake also increased the production of superoxide in the NTS. The results of this study suggest that fructose might induce central insulin resistance and elevate BP by enhancing superoxide production and activating p38 phosphorylation in the NTS.

Graphical abstract

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The Computerized Perceptual Motor Skills Assessment: A new visual perceptual motor skills evaluation tool for children in early elementary grades

Publication date: October 2017
Source:Research in Developmental Disabilities, Volume 69
Author(s): Tsu-Hsin Howe, Hao-Ling Chen, Candy Chieh Lee, Ying-Dar Chen, Tien-Ni Wang
Visual perceptual motor skills have been proposed as underlying courses of handwriting difficulties. However, there is no evaluation tool currently available to assess these skills comprehensively and to serve as a sensitive measure. The purpose of this study was to validate the Computerized Perceptual Motor Skills Assessment (CPMSA), a newly developed evaluation tool for children in early elementary grades. Its test-retest reliability, concurrent validity, discriminant validity, and responsiveness were examined in 43 typically developing children and 26 children with handwriting difficulty. The CPMSA demonstrated excellent reliability across all subtests with intra-class correlation coefficients (ICCs)≥0.80. Significant moderate correlations between the domains of the CPMSA and corresponding gold standards including Beery VMI, the TVPS-3, and the eye-hand coordination subtest of the DTVP-2 demonstrated good concurrent validity. In addition, the CPMSA showed evidence of discriminant validity in samples of children with and without handwriting difficulty. This article provides evidence in support of the CPMSA. The CPMSA is a reliable, valid, and promising measure of visual perceptual motor skills for children in early elementary grades. Directions for future study and improvements to the assessment are discussed.



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Comparison of the Efficacy of Tenofovir Versus Tenofovir plus Entecavir in the Treatment of Chronic Hepatitis B in Patients With Poor Efficacy of Entecavir: A Systematic Review and Meta-analysis

Publication date: Available online 7 August 2017
Source:Clinical Therapeutics
Author(s): Jun Chen, Shu-Shan Zhao, Xiao-xiao Liu, Ze-Bing Huang, Yan Huang
PurposeThis study aimed to compare the efficacy between tenofovir disoproxil fumarate (TDF) and TDF plus entecavir (ETV) combination therapy in patients with chronic hepatitis B (CHB) with a poor response to ETV.MethodsWe searched the China National Knowledge Infrastructure (CNKI), PubMed, EMBASE, and SCOPE libraries for articles using the keywords chronic hepatitis B virus or CHB or HBV, entecavir or ETV, and tenofovir or TDF.FindingsFive studies (from CNKI and PubMed) with a total of 408 patients met the inclusion criteria: 212 patients in the TDF group and 196 patients in the TDF plus ETV group. The rates of viral suppression between the 2 groups were comparable at weeks 24 and 48 of treatment (P = 0.546 vs P = 0.818). In addition, the subanalysis revealed that no significant differences were observed in the rates of viral suppression between the 2 groups at week 24 (subgroup 1 [partial response to ETV]: P = 0.822; subgroup 2 [resistance to ETV]: P = 0.294) and week 48 (subgroup 1: P = 0.797; subgroup 2: P = 0.545). No significant differences were found in alanine aminotransferase normalization, hepatitis B e antigen loss, hepatitis B e antigen seroconversion, virologic breakthrough, and tolerability between the 2 groups at weeks 24 and 48. Therefore, the results suggest that TDF monotherapy should be chosen for patients with CHB with a poor response to ETV for reasons of economy and convenience.ImplicationsWe conclude that TDF monotherapy is comparable to TDF-ETV combination therapy for patients with a poor response to ETV; thus, TDF monotherapy may be a better choice for these patients. However, because of the limited citations in this meta-analysis, complete and systematic evidence is needed to evaluate the differences in efficacy and tolerability between TDF and TDF-ETV. Larger and longer randomized clinical trials and further studies should be conducted to verify the results.



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Levofloxacin is phytotoxic and modifies the protein profile of lupin seedlings

Abstract

The toxicity of levofloxacin to yellow lupin plants was evaluated in this study. Recommended indexes of plant (roots and shoots) growth were determined and new indexes were proposed which better characterise the phytotoxicity of levofloxacin. These were, in particular, the activity of antioxidative enzymes, the content of free radicals, as well as the root protein content and the root protein profile. The results showed that levofloxacin considerably affected EC₅₀, measured as the activity of catalase in roots, and leaves (1.05 and 0.069 mM, respectively). The activity of peroxidase in the roots and the dry weight of seedlings were the least sensitive parameters (EC₅₀ was 1.8 and 1.76 mM, respectively). Units of toxicity clearly showed that the activity of catalase is a better measure of toxicity for low concentrations of the drug, and it is a better index of plant physiological state than the morphological parameters of seedlings. Moreover, levofloxacin changed the location of free radicals and the protein profile in plants. The changes in location of reactive oxygen species in roots were an important symptom of the drug toxicity to lupin seedlings. Our results have shown that the toxicity of levofloxacin was manifested mainly by changes in the protein profile. The content of the glyceraldehyde-3-phosphate dehydrogenase, 14-3-3-like protein A, expansin-B3-like precursor, fructose-bisphosphate aldolase, lipoxygenase, nucleotide-binding subunit of vacuolar ATPase and pyruvate dehydrogenase were found to decrease. On the other hand, plant exposure to levofloxacin resulted in an increase in the content of enolase, protein LlR18A, class III chitinase, ascorbate peroxidase, aspartate aminotransferase, alcohol dehydrogenase 1, leghemoglobin reductase-like 17 and heat shock cognate protein 80-like.

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Cytoskeleton and nuclear lamina affection in recessive osteogenesis imperfecta: A functional proteomics perspective

Publication date: Available online 9 August 2017
Source:Journal of Proteomics
Author(s): Assunta Gagliardi, Roberta Besio, Chiara Carnemolla, Claudia Landi, Alessandro Armini, Mona Aglan, Ghada Otaify, Samia A. Temtamy, Antonella Forlino, Luca Bini, Laura Bianchi
Osteogenesis imperfecta (OI) is a collagen-related disorder associated to dominant, recessive or X-linked transmission, mainly caused by mutations in type I collagen genes or in genes involved in type I collagen metabolism.Among the recessive forms, OI types VII, VIII, and IX are due to mutations in CRTAP, P3H1, and PPIB genes, respectively. They code for the three components of the endoplasmic reticulum complex that catalyzes 3-hydroxylation of type I collagen α1Pro986. Under-hydroxylation of this residue leads to collagen structural abnormalities and results in moderate to lethal OI phenotype, despite the exact molecular mechanisms are still not completely clear.To shed light on these recessive forms, primary fibroblasts from OI patients with mutations in CRTAP (n=3), P3H1 (n=3), PPIB (n=1) genes and from controls (n=4) were investigated by a functional proteomic approach. Cytoskeleton and nucleoskeleton asset, protein fate, and metabolism were delineated as mainly affected. While western blot experiments confirmed altered expression of lamin A/C and cofilin-1, immunofluorescence analysis using antibody against lamin A/C and phalloidin showed an aberrant organization of nucleus and cytoskeleton.This is the first report describing an altered organization of intracellular structural proteins in recessive OI and pointing them as possible novel target for OI treatment.SignificanceOI is a prototype for skeletal dysplasias. It is a highly heterogeneous collagen-related disorder with dominant, recessive and X-linked transmission. There is no definitive cure for this disease, thus a better understanding of the molecular basis of its pathophysiology is expected to contribute in identifying potential targets to develop new treatments.Based on this concept, we performed a functional proteomic study to delineate affected molecular pathways in primary fibroblasts from recessive OI patients, carrying mutations in CRTAP (OI type VII), P3H1 (OI type VIII), and PPIB (OI type IX) genes. Our analyses demonstrated the occurrence of an altered cytoskeleton and, for the first time in OI, of nuclear lamina organization. Hence, cytoskeleton and nucleoskeleton components may be considered as novel drug targets for clinical management of the disease.Finally, according to our analyses, OI emerged to share similar deregulated pathways and molecular aberrances, as previously described, with other rare disorders caused by different genetic defects.Those aberrances may provide common pharmacological targets to support classical clinical approach in treating different diseases.

Graphical abstract

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Label-free quantitative proteomic analysis of Lactobacillus fermentum NCDC 400 during bile salt exposure

Publication date: Available online 9 August 2017
Source:Journal of Proteomics
Author(s): Gurjeet Kaur, Syed Azmal Ali, Sudarshan Kumar, Ashok Kumar Mohanty, Pradip Behare
Lactobacillus fermentum NCDC 400 is a commonly used and a comprehensively studied probiotic organism. The distinctive capability to endure the harsh environment of the gastrointestinal tract owing to the presence of bile salts in gastric juice facilitates gut microbiota, especially the probiotic organisms to transiently inhabit the host gut. In the present study, Label-Free Quantification (LFQ) approach has been employed to analyze the expression pattern of Lactobacillus fermentum NCDC 400 strain proteins, under bile acid stress, using high-resolution mass spectrometer connected to nano-liquid chromatography (LC) system. We report the identification of a total of 538 differentially expressed (DE) proteins in response to 1.2% bile salt which is required for the growth of this bacterium. Among the DE proteins, 80 were found to be up-regulated, with greater than 1.3 fold change vis-à-vis 107 proteins which were down-regulated with <0.76 fold change (p<0.05). The functions of down-regulated proteins were largely unknown nevertheless; the putative functions of the up-regulated proteins were categorized into categories viz. stress response, DNA repair, peptidoglycan biosynthesis, amino acids metabolism, signal transduction, transcription, translation, and carbohydrate metabolism. These results suggest that the differentially expressed proteins provide the tolerance towards the various gastrointestinal challenges and involved in bile acid stress response mechanism.

Graphical abstract

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Synthesis, vibrational spectrometry and thermal characterizations of coordination polymers derived from divalent metal ions and hydroxyl terminated polyurethane as ligand

Publication date: 5 January 2018
Source:Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Volume 188
Author(s): Laxmi, Shabnam Khan, Abdul Kareem, Fahmina Zafar, Nahid Nishat
A series of novel coordination polyurethanes [HTPU-M, where M=Mn(II) 'd⁵', Ni(II) 'd⁸', and Zn(II) 'd¹⁰'] have been synthesized to investigate the effect of divalent metal ions coordination on structure, thermal and adsorption properties of low molecular weight hydroxyl terminated polyurethane (HTPU). HTPU-M have been synthesized in situ where, OH group of HTPU (synthesized by the condensation polymerization reaction of ethylene glycol (EG) and toluene diisocyanate (TDI) in presence of catalyst) on condensation polymerization with metal acetate in presence of acid catalyst synthesized HTPU-M followed by coordination of metal ions with hetero atoms. The structure, composition and geometry of HTPU-M have been confirmed by vibrational spectrometry (FTIR), ¹H NMR, elemental analysis and UV–Visible spectroscopy. Morphological structures of HTPU-M were analyzed by X-Ray Diffraction analysis (XRD), Field Emission Scanning Electron Microscope (FE-SEM) with Energy Dispersive X-ray spectroscopy (EDX) and High Resolution Transmission Electron Microscope (HR-TEM) techniques. The thermal degradation pattern and thermal stability of HTPU-M in comparison to HTPU was investigated by thermal-gravimetric (TG)/differential thermal (DT), analyses along with Integral procedure decomposition temperature (IPDT) by Doyle method. The molecular weight of HTPU was determined by gel permeation chromatography (GPC). The preliminary adsorption/desorption studies of HTPU-M for Congo red (CR) was studied by batch adsorption techniques.The results indicated that HTPU-M have amorphous, layered morphology with higher number of nano-sized grooves in comparison to HTPU. Coordination of metal to HTPU plays a key role in enhancing the thermal stability [HTPU-Ni(II)>HTPU-Mn(II)>HTPU-Zn(II)>HTPU]. The HTPU-M can be utilized for industrial waste water treatment by removing environmental pollutants.

Graphical abstract

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Tissue magnetic susceptibility mapping as a marker of tau pathology in Alzheimer's disease

Publication date: 1 October 2017
Source:NeuroImage, Volume 159
Author(s): J. O'Callaghan, H. Holmes, N. Powell, J.A. Wells, O. Ismail, I.F. Harrison, B. Siow, R. Johnson, Z. Ahmed, A. Fisher, S. Meftah, M.J. O'Neill, T.K. Murray, E.C. Collins, K. Shmueli, M.F. Lythgoe
Alzheimer's disease is connected to a number of other neurodegenerative conditions, known collectively as 'tauopathies', by the presence of aggregated tau protein in the brain. Neuroinflammation and oxidative stress in AD are associated with tau pathology and both the breakdown of axonal sheaths in white matter tracts and excess iron accumulation grey matter brain regions. Despite the identification of myelin and iron concentration as major sources of contrast in quantitative susceptibility maps of the brain, the sensitivity of this technique to tau pathology has yet to be explored. In this study, we perform Quantitative Susceptibility Mapping (QSM) and T2* mapping in the rTg4510, a mouse model of tauopathy, both in vivo and ex vivo. Significant correlations were observed between histological measures of myelin content and both mean regional magnetic susceptibility and T2* values. These results suggest that magnetic susceptibility is sensitive to tissue myelin concentrations across different regions of the brain. Differences in magnetic susceptibility were detected in the corpus callosum, striatum, hippocampus and thalamus of the rTg4510 mice relative to wild type controls. The concentration of neurofibrillary tangles was found to be low to intermediate in these brain regions indicating that QSM may be a useful biomarker for early stage detection of tau pathology in neurodegenerative diseases.



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Bilinguals have more complex EEG brain signals in occipital regions than monolinguals

Publication date: 1 October 2017
Source:NeuroImage, Volume 159
Author(s): John G. Grundy, John A.E. Anderson, Ellen Bialystok
Brain signal complexity increases with development and is associated with better cognitive outcomes in older age. Research has also shown that bilinguals are able to stave off cognitive decline for longer periods of time than monolinguals, but no studies to date have examined whether bilinguals have more complex brain signals than monolinguals. Here we explored the hypothesis that bilingualism leads to greater brain signal complexity by examining multiscale entropy (MSE) in monolingual and bilingual young adults while EEG was recorded during a task-switching paradigm. Results revealed that bilinguals had greater brain signal complexity than monolinguals in occipital regions. Furthermore, bilinguals performed better with increasing occipital brain signal complexity, whereas monolinguals relied on coupling with frontal regions to demonstrate gains in performance. These findings are discussed in terms of how a lifetime of experience with a second language leads to more automatic and efficient processing of stimuli and how these adaptations could contribute to the prevention of cognitive decline in older age.



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Task modulates functional connectivity networks in free viewing behavior

Publication date: 1 October 2017
Source:NeuroImage, Volume 159
Author(s): Hossein Seidkhani, Andrey R. Nikolaev, Radha Nila Meghanathan, Hamid Pezeshk, Ali Masoudi-Nejad, Cees van Leeuwen
In free visual exploration, eye-movement is immediately followed by dynamic reconfiguration of brain functional connectivity. We studied the task-dependency of this process in a combined visual search-change detection experiment. Participants viewed two (nearly) same displays in succession. First time they had to find and remember multiple targets among distractors, so the ongoing task involved memory encoding. Second time they had to determine if a target had changed in orientation, so the ongoing task involved memory retrieval. From multichannel EEG recorded during 200 ms intervals time-locked to fixation onsets, we estimated the functional connectivity using a weighted phase lag index at the frequencies of theta, alpha, and beta bands, and derived global and local measures of the functional connectivity graphs. We found differences between both memory task conditions for several network measures, such as mean path length, radius, diameter, closeness and eccentricity, mainly in the alpha band. Both the local and the global measures indicated that encoding involved a more segregated mode of operation than retrieval. These differences arose immediately after fixation onset and persisted for the entire duration of the lambda complex, an evoked potential commonly associated with early visual perception. We concluded that encoding and retrieval differentially shape network configurations involved in early visual perception, affecting the way the visual input is processed at each fixation. These findings demonstrate that task requirements dynamically control the functional connectivity networks involved in early visual perception.



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Assessment and elimination of the effects of head movement on MEG resting-state measures of oscillatory brain activity

Publication date: 1 October 2017
Source:NeuroImage, Volume 159
Author(s): Eirini Messaritaki, Loes Koelewijn, Diana C. Dima, Gemma M. Williams, Gavin Perry, Krish D. Singh
Magnetoencephalography (MEG) is increasingly being used to study brain function because of its excellent temporal resolution and its direct association with brain activity at the neuronal level. One possible cause of error in the analysis of MEG data comes from the fact that participants, even MEG-experienced ones, move their head in the MEG system. Head movement can cause source localization errors during the analysis of MEG data, which can result in the appearance of source variability that does not reflect brain activity. The MEG community places great importance in eliminating this source of possible errors as is evident, for example, by recent efforts to develop head casts that limit head movement in the MEG system. In this work we use software tools to identify, assess and eliminate from the analysis of MEG data any possible correlations between head movement in the MEG system and widely-used measures of brain activity derived from MEG resting-state recordings. The measures of brain activity we study are a) the Hilbert-transform derived amplitude envelope of the beamformer time series and b) functional networks; both measures derived by MEG resting-state recordings. Ten-minute MEG resting-state recordings were performed on healthy participants, with head position continuously recorded. The sources of the measured magnetic signals were localized via beamformer spatial filtering. Temporal independent component analysis was subsequently used to derive resting-state networks.Significant correlations were observed between the beamformer envelope time series and head movement. The correlations were substantially reduced, and in some cases eliminated, after a participant-specific temporal high-pass filter was applied to those time series. Regressing the head movement metrics out of the beamformer envelope time series had an even stronger effect in reducing these correlations. Correlation trends were also observed between head movement and the activation time series of the default-mode and frontal networks. Regressing the head movement metrics out of the beamformer envelope time series completely eliminated these correlations. Additionally, applying the head movement correction resulted in changes in the network spatial maps for the visual and sensorimotor networks. Our results a) show that the results of MEG resting-state studies that use the above-mentioned analysis methods are confounded by head movement effects, b) suggest that regressing the head movement metrics out of the beamformer envelope time series is a necessary step to be added to these analyses, in order to eliminate the effect that head movement has on the amplitude envelope of beamformer time series and the network time series and c) highlight changes in the connectivity spatial maps when head movement correction is applied.

Graphical abstract

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Considering healthiness promotes healthier choices but modulates medial prefrontal cortex differently in children compared with adults

Publication date: 1 October 2017
Source:NeuroImage, Volume 159
Author(s): Floor van Meer, Laura N. van der Laan, Max A. Viergever, Roger A.H. Adan, Paul A.M. Smeets
Childhood obesity is a rising problem worldwide mainly caused by overconsumption, which is driven by food choices. In adults, food choices are based on a value signal encoded in the medial prefrontal cortex (mPFC). This signal is modulated by the dorsolateral prefrontal cortex (dlPFC), which is involved in self-control.We aimed to examine the neural correlates of food choice in children, and how considering healthiness affects neural activity and choice behavior.24 children and 28 adults performed a food choice task while being scanned with fMRI and provided health and taste ratings of the foods afterwards. During the choice task participants considered either the healthiness or tastiness of the food or chose naturally.Health rating was a positive predictor of choice in adults, but a negative predictor in children. Children had weaker dlPFC activation than adults during yes vs. no independent of health or taste condition. Both children and adults made healthier choices when considering healthiness. Taste rating modulated mPFC activation in both children and adults. When considering the healthiness, health rating positively modulated mPFC activation in adults, but negatively in children. Considering the healthiness increased connectivity between dlPFC and mPFC in adults, but not in children.In conclusion, considering healthiness can promote healthier choices in both children and adults, but is accompanied by an opposing pattern of brain activation in the mPFC. Since the absolute number of healthy choices remained lower in children, this suggests that children may not yet be geared to modify their choices away from their natural tendency to choose unhealthy tasty foods. Thus, this study suggests that it may be promising to develop interventions that increase children's preference for healthy food, for example by increasing the habitual consumption of healthy foods from a young age.



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Biomonitoring of coastal pollution in the Gulf of Gabes (SE, Tunisia): use of Posidonia oceanica seagrass as a bioindicator and its mat as an archive of coastal metallic contamination

Abstract

Within the framework of a study on the extent and history of marine pollution in the central area of Gabes Gulf, the concentrations of four trace metals (Cd, Cu, Pb, and Zn) were assessed in three different tissues of the seagrass species, Posidonia oceanica (leaves, rhizomes, and roots), in the mat of P. oceanica meadows at different depths from the sea floor (− 30 to − 150 cm) and in sediments. The results showed that P. oceanica leaves accumulate more Cd, Cu, and Zn, whereas Pb was found to be more concentrated in roots. The analysis of P. oceanica mat highlighted a clear decreasing gradient of trace metal concentrations from lower (− 30 cm) to higher (− 150 cm) depths. Considering that P. oceanica mat continuously rises above the initial level, with a rate of 1 m per century (~1 cm year⁻¹; Molinier and Picard Ann Inst Océanogr Fr 27:157–234, 1952), the latter observation suggested that the pollution level in Gabes Gulf increased continuously during the last few decades. The results of the P. oceanica mapping in the study area showed a continuous regression of its meadows as well as its local disappearance from various areas in the central part of Gabes Gulf. The current status of P. oceanica is most likely due to the cumulative effects of the discharges from the coastal industrial complex of Gabes-Ghannouche represented mainly by the phosphogypsum discharges. This study confirms the usefulness of P. oceanica not only as a bioindicator of the "health status" of coastal ecosystems but also as a record register tracing back the history and temporal evolution of coastal contamination level.

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La Cascada Declaration

Abstract

We are a group of senior scientists—researchers, academics and intellectuals—from various parts of the world, with over 250 years' combined experience of working to improve the oral health of communities. The group is entirely independent of any institution, government body or corporate entity.

This article is protected by copyright. All rights reserved.

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Graphene: A Versatile Platform for Nanotheranostics and Tissue Engineering

Publication date: Available online 9 August 2017
Source:Progress in Materials Science
Author(s): Renu Geetha Bai, Neethu Ninan, Kasturi Muthoosamy, Sivakumar Manickam
The sustained extensive research on graphene and its derivatives in the last decade portrayed its significance in the field of material science and carved its own niche in nanotechnology. Starting from the simple pencil, the role of graphene now extends to a lifesaver through innovations in nanomedicine specifically the early detection of abnormalities and efficient treatments. Graphene has the potential to satisfy the nanotechnological concepts of personalized and regenerative medicine for a disease-free future. The functionalization techniques ameliorate graphene for improved solubility, stability, loading capacity, etc. which makes it an ideal nanosystem for theranostic applications such as biosensing, drug delivery, gene therapy, bioimaging, phototherapy and hybrid theranostics. In addition, due to its electrically tunable surface chemistry, maximal surface-to-volume ratio, easy functionalization capacity and mechanical robustness, graphene gained enormous attention in tissue engineeringspecifically in cardiac, nerve, bone, skin and stem cells. This review focusses on the recent developments in graphene-based nanotheranostics and tissue engineering, which reveals the hidden potential of modern medical notions in efficiently handling the variety of abnormalities. Moreover, it raises the necessity of successful therapeutic systems to transfer from bench-to-bedside through clinical trials to enhance the current treatment scenario.

Graphical abstract

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Facing the facts: The Runx2 gene is associated with variation in facial morphology in primates

Publication date: October 2017
Source:Journal of Human Evolution, Volume 111
Author(s): Terrence B. Ritzman, Nicholas Banovich, Kaitlin P. Buss, Jennifer Guida, Meagan A. Rubel, Jennifer Pinney, Bao Khang, Matthew J. Ravosa, Anne C. Stone
The phylogenetic and adaptive factors that cause variation in primate facial form—including differences among the major primate clades and variation related to feeding and/or social behavior—are relatively well understood. However, comparatively little is known about the genetic mechanisms that underlie diversity in facial form in primates. Because it is essential for osteoblastic differentiation and skeletal development, the runt-related transcription factor 2 (Runx2) is one gene that may play a role in these genetic mechanisms. Specifically, polymorphisms in the QA ratio (determined by the ratio of the number of polyglutamines to polyalanines in one functional domain of Runx2) have been shown to be correlated with variation in facial length and orientation in other mammal groups. However, to date, the relationship between variation in this gene and variation in facial form in primates has not been explicitly tested. To test the hypothesis that the QA ratio is correlated with facial form in primates, the current study quantified the QA ratio, facial length, and facial angle in a sample of 33 primate species and tested for correlation using phylogenetic generalized least squares. The results indicate that the QA ratio of the Runx2 gene is positively correlated with variation in relative facial length in anthropoid primates. However, no correlation was found in strepsirrhines, and there was no correlation between facial angle and the QA ratio in any groups. These results suggest that, in primates, the QA ratio of the Runx2 gene may play a role in modulating facial size, but not facial orientation. This study therefore provides important clues about the genetic and developmental mechanisms that may underlie variation in facial form in primates.



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