Publication date: Available online 4 April 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Kate Gardner Burt, Pamela Koch, Isobel Contento
BackgroundResearchers have established the benefits of school gardens on students' academic achievement, dietary outcomes, physical activity, and psychosocial skills, yet limited research has been conducted about how school gardens become institutionalized and sustained.ObjectiveOur aim was to develop a tool that captures how gardens are effectively established, integrated, and sustained in schools.DesignWe conducted a sequential, exploratory, mixed-methods study. Participants were identified with the help of Grow To Learn, the organization coordinating the New York City school garden initiative, and recruited via e-mail.Participants/settingA stratified, purposeful sample of 21 New York City elementary and middle schools participated in this study throughout the 2013/2014 school year. The sample was stratified in their garden budgets and purposeful in that each of the schools' gardens were determined to be well integrated and sustained.Main outcome measuresThe processes and strategies used by school gardeners to establish well-integrated school gardens were assessed via data collected from surveys, interviews, observations, and concept mapping.Statistical analyses performedDescriptive statistics as well as multidimensional scaling and hierarchical cluster analysis were used to examine the survey and concept mapping data. Qualitative data analysis consisted of thematic coding, pattern matching, explanation building and cross-case synthesis.ResultsNineteen components within four domains of school garden integration were found through the mixed-methods concept mapping analysis. When the analyses of other data were combined, relationships between domains and components emerged. These data resulted in the development of the GREEN (Garden Resources, Education, and Environment Nexus) Tool.ConclusionsWhen schools with integrated and sustained gardens were studied, patterns emerged about how gardeners achieve institutionalization through different combinations of critical components. These patterns are best described by the GREEN Tool, the first framework to identify how to operationalize school gardening components and describe an evidence-based strategy of successful school garden integration.
http://ift.tt/2nVZIf7
Τρίτη 4 Απριλίου 2017
Development of the GREEN (Garden Resources, Education, and Environment Nexus) Tool: An Evidence-Based Model for School Garden Integration
Components of the Hanging Columella: Strategies for Refinement.
http://ift.tt/2nIwsYm
Simplifying the Forehead Flap for Nasal Reconstruction: A review of 420 consecutive cases.
http://ift.tt/2oBJkDg
A National Study of the Impact of Delayed Flap Timing for Treatment of Patients with Deep Sternal Wound Infection.
http://ift.tt/2oBFJFh
New cranium of the endemic Caribbean platyrrhine, Antillothrix bernensis, from La Altagracia Province, Dominican Republic
Source:Journal of Human Evolution, Volume 106
Author(s): Lauren B. Halenar, Siobhán B. Cooke, Alfred L. Rosenberger, Renato Rímoli
Recent paleontological collection in submerged caves in the eastern Dominican Republic has yielded new specimens of Antillothrix bernensis. Here we describe a complete cranium of an adult individual (MHD 20) and provide phenetic comparisons to other endemic Caribbean taxa and extant mainland platyrrhines using three-dimensional geometric morphometric methods (3DGM). Qualitative and quantitative comparisons support conclusions based on other recently described fossil material: Antillothrix has a dentition lacking clear dietary specialization, an elongated brain case with strong temporal lines, and a vertically oriented nuchal plane. MHD 20 shares a combination of traits with a previously published subadult specimen (MHD 01) including a deep depression at glabella, dorsoventrally elongated orbits, and a relatively large face. This shared morphology reinforces the taxonomic affinity of the two specimens, with differences between the two likely reflecting the younger ontogenetic age of MHD 01.Comparisons to the extant platyrrhines paint a complicated picture as the results of between-group principal components analyses (bgPCA) indicate that Antillothrix does not share a suite of morphological features exclusively with any one genus. Depending on which bgPC axes are visualized, and which subset of landmarks is included (i.e., only those describing the shape of the face/palate for inclusion of Xenothrix), MHD 20 is most similar in shape to the atelids, Alouatta, Lagothrix, and Brachyteles, or an otherwise "empty" region of shape space. It groups neither with Cebus nor Callicebus, two taxa that Antillothrix has been associated with in previous studies based on much less complete material. The Antillothrix cranium does not exhibit any of the derived characters classically used to diagnose or define any single clade; rather its morphology shares features with multiple platyrrhine groups. This is consistent with the interpretation that Antillothrix preserves a primitive morphology, which accords with the hypothesis positing an early arrival of platyrrhines in the Caribbean.
http://ift.tt/2nIIalC
Seeds in the liver
Source:Acta Histochemica
Author(s): Hongjie Ji, Yanrong Lu, Yujun Shi
The liver is a crucial organ for homeostasis and has a tremendous self-renewal and regenerative capacity. It has long been believed that the self-renewal and repair of the liver within a given physiological condition or its repopulation in chronic liver diseases, when hepatocyte proliferation is impaired, will primarily be conducted by the proliferating duct cells, termed "oval cells" or hepatic progenitor cells (HPCs). In addition, numerous studies have revealed that HPCs are the initial tumor cells of liver cancer under certain micro-environments. However, benefit from the extensive application of lineage tracing strategies using the Cre/LoxP system, researchers have redefined the fate of these bipotential cells, raising obvious controversies regarding the capacity of liver cells to control their own biology and differentiation. Here, we review the relevant articles, focusing on cell-lineage tracing to better understanding seed cells and their distinct fate in the liver.
http://ift.tt/2oGS6gJ
Elongated Dorsal Nasal Flap to Reconstruct Large Defects of the Nose.
http://ift.tt/2oGU3JZ
Striae Distensae: Preventative and Therapeutic Modalities to Improve Aesthetic Appearance.
http://ift.tt/2oAiuf9
IncobotulinumtoxinA for Aesthetic Indications: A Systematic Review of Prospective Comparative Trials.
http://ift.tt/2oGPizU
Creation and Validation of a Photonumeric Scale to Assess Volume Deficiency in the Infraorbital Region.
http://ift.tt/2oAuCNw
Autologous Pure Platelet-Rich Plasma Dermal Injections for Facial Skin Rejuvenation: Clinical, Instrumental, and Flow Cytometry Assessment.
http://ift.tt/2oGVSqc
Advancing Keloid Treatment: A Novel Multimodal Approach to Ear Keloids.
http://ift.tt/2oAwBRW
Primary Cutaneous Follicular Helper T-Cell Lymphoma: A Case Series and Review of the Literature.
http://ift.tt/2nCFsxi
Commentary on Some Recent Theses Relevant to Combating Aging: April 2017
Rejuvenation Research , Vol. 0, No. 0.
http://ift.tt/2nI2Ydg
Multiple cutaneous reticulohistiocytosis with T-cell large granular lymphocyte clonopathy
Abstract
A 63-year-old Caucasian man presented with a 4-month history of disseminated asymptomatic reddish-brown papulonodular lesions. A skin biopsy showed dermal infiltration with CD68+ histiocytes, predominantly with eosinophilic cytoplasm, some with a ground-glass cytoplasm, and a small number of giant cells. The diagnosis of multiple cutaneous reticulohistiocytosis was made. Bone marrow immunophenotyping due to peripheral blood lymphocytosis revealed the presence of a monoclonal population of CD3+, CD8+ CD57+ large granular lymphocytes. The present case suggests the coexistence of multiple cutaneous reticulohistiocytosis with an underlying disorder.
http://ift.tt/2oAjcZW
Biologics,Biologic Response Modifiers,Biopharmaceutical.
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
Contractile force generation by 3D hiPSC-derived cardiac tissues is enhanced by rapid establishment of cellular interconnection in matrix with muscle-mimicking stiffness
Source:Biomaterials, Volume 131
Author(s): Soah Lee, Vahid Serpooshan, Xinming Tong, Sneha Venkatraman, Meelim Lee, Jaecheol Lee, Orlando Chirikian, Joseph C. Wu, Sean M. Wu, Fan Yang
Engineering 3D human cardiac tissues is of great importance for therapeutic and pharmaceutical applications. As cardiac tissue substitutes, extracellular matrix-derived hydrogels have been widely explored. However, they exhibit premature degradation and their stiffness is often orders of magnitude lower than that of native cardiac tissue. There are no reports on establishing interconnected cardiomyocytes in 3D hydrogels at physiologically-relevant cell density and matrix stiffness. Here we bioengineer human cardiac microtissues by encapsulating human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in chemically-crosslinked gelatin hydrogels (1.25 × 108/mL) with tunable stiffness and degradation. In comparison to the cells in high stiffness (16 kPa)/slow degrading hydrogels, hiPSC-CMs in low stiffness (2 kPa)/fast degrading and intermediate stiffness (9 kPa)/intermediate degrading hydrogels exhibit increased intercellular network formation, α-actinin and connexin-43 expression, and contraction velocity. Only the 9 kPa microtissues exhibit organized sarcomeric structure and significantly increased contractile stress. This demonstrates that muscle-mimicking stiffness together with robust cellular interconnection contributes to enhancement in sarcomeric organization and contractile function of the engineered cardiac tissue. This study highlights the importance of intercellular connectivity, physiologically-relevant cell density, and matrix stiffness to best support 3D cardiac tissue engineering.
http://ift.tt/2nA2epI
Microfluidic-enhanced 3D bioprinting of aligned myoblast-laden hydrogels leads to functionally organized myofibers in vitro and in vivo
Publication date: July 2017
Source:Biomaterials, Volume 131
Author(s): Marco Costantini, Stefano Testa, Pamela Mozetic, Andrea Barbetta, Claudia Fuoco, Ersilia Fornetti, Francesco Tamiro, Sergio Bernardini, Jakub Jaroszewicz, Wojciech Święszkowski, Marcella Trombetta, Luisa Castagnoli, Dror Seliktar, Piotr Garstecki, Gianni Cesareni, Stefano Cannata, Alberto Rainer, Cesare Gargioli
We present a new strategy for the fabrication of artificial skeletal muscle tissue with functional morphologies based on an innovative 3D bioprinting approach. The methodology is based on a microfluidic printing head coupled to a co-axial needle extruder for high-resolution 3D bioprinting of hydrogel fibers laden with muscle precursor cells (C2C12). To promote myogenic differentiation, we formulated a tailored bioink with a photocurable semi-synthetic biopolymer (PEG-Fibrinogen) encapsulating cells into 3D constructs composed of aligned hydrogel fibers. After 3–5 days of culture, the encapsulated myoblasts started migrating and fusing, forming multinucleated myotubes within the 3D bioprinted fibers. The obtained myotubes showed high degree of alignment along the direction of hydrogel fiber deposition, further revealing maturation, sarcomerogenesis, and functionality. Following subcutaneous implantation in the back of immunocompromised mice, bioprinted constructs generated organized artificial muscle tissue in vivo. Finally, we demonstrate that our microfluidic printing head allows to design three dimensional multi-cellular assemblies with an exquisite compartmentalization of the encapsulated cells. Our results demonstrate an enhanced myogenic differentiation with the formation of parallel aligned long-range myotubes. The approach that we report here represents a robust and valid candidate for the fabrication of macroscopic artificial muscle to scale up skeletal muscle tissue engineering for human clinical application.
http://ift.tt/2o5Etto
Raman spectroscopy for the detection of organ distribution and clearance of PEGylated reduced graphene oxide and biological consequences
Publication date: July 2017
Source:Biomaterials, Volume 131
Author(s): Santhakumar Syama, Willi Paul, Arumugam Sabareeswaran, Parayanthala Valappil Mohanan
Graphene, a 2D carbon material has found vast application in biomedical field because of its exciting physico-chemical properties. The large planar sheet like structure helps graphene to act as an effective carrier of drug or biomolecules in enormous amount. However, limited data available on the biocompatibility of graphene upon interaction with the biological system prompts us to evaluate their toxicity in animal model. In this study organ distribution, clearance and toxicity of PEGylated reduced nanographene (PrGO) on Swiss Albino mice was investigated after intraperitoneal and intravenous administration. Biodistribution and blood clearance was monitored using confocal Raman mapping and indicated that PrGO was distributed on major organs such as brain, liver, kidney, spleen and bone marrow. Presence of PrGO in brain tissue suggests that it has the potential to cross blood brain barrier. Small amount of injected PrGO was found to excrete via urine. Repeated administration of PrGO induced acute liver injury, congestion in kidney and increased splenocytes proliferation in days following exposure. Hence the result of the study recommended that PrGO should undergo intensive safety assessment before clinical application or validated to be safe for medical use.
Graphical abstract
http://ift.tt/2o1cmLs
Magnetic and thermal transport properties of SrFe12O19 permanent magnets with anisotropic grain structure
Publication date: 5 July 2017
Source:Materials & Design, Volume 125
Author(s): A.D. Volodchenkov, S. Ramirez, R. Samnakay, R. Salgado, Y. Kodera, A.A. Balandin, J.E. Garay
Permanent magnets are gaining increasing interest and importance for applications such as generators and motors. Thermal management is a key concern since performance of magnets decreases with temperature. We investigate the magnetic and thermal transport properties of rare earth-free, fine-grained SrFe12O19 magnets produced by the current activated pressure assisted densification. We propose a cooling scheme based on an anisotropic grain structure that can help retain magnetic performance under high temperature conditions. The synthesized magnets have aligned grains such that their magnetic easy axis is perpendicular to their largest surface area to maximize their magnetic performance. The SrFe12O19 magnets have fine grain sizes in the cross-plane direction and substantially larger grain sizes in the in-plane direction. This microstructure results in approximately a factor of two higher thermal conductivity in the in-plane direction, providing an opportunity for effective cooling. The phonons are the dominant heat carriers near room temperature. Temperature and direction dependent thermal conductivity measurements indicate that both Umklapp and grain boundary scattering are important in the in-plane direction, while grain boundary scattering dominates the cross-plane thermal transport. The proposed design strategy should translate well to other material systems and has important implications for thermal management of nanostructured permanent magnets.
Graphical abstract
http://ift.tt/2n9iNNS
Functionally graded shape memory alloys: Design, fabrication and experimental evaluation
Publication date: 15 June 2017
Source:Materials & Design, Volume 124
Author(s): Bashir S. Shariat, Qinglin Meng, Abdus S. Mahmud, Zhigang Wu, Reza Bakhtiari, Junsong Zhang, Fakhrodin Motazedian, Hong Yang, Gerard Rio, Tae-hyun Nam, Yinong Liu
Functionally graded shape memory alloys have the advantage of combining the functionalities of the shape memory effect and those of functionally graded structures. By proper design, they can exhibit new and complex deformation behaviour that is unmatched in uniform shape memory alloys. One obvious advantage of functionally graded shape memory alloys is their widened transformation stress and temperature windows that provide improved controllability in actuating applications. This paper reports on the concept, fabrication, experimentation and thermomechanical behaviour of several designs of functionally graded NiTi alloys, including compositionally graded, microstructurally graded and geometrically graded NiTi alloys, and the various techniques that may be used to create these functionally graded materials. It is found that the property gradients created along the loading direction or perpendicular to the loading direction produce distinct thermomechanical behaviours. The property gradient along the loading direction provides stress gradient over stress-induced transformation, which can be adjusted by the property gradient profile. The property gradient through the thickness direction of plate specimens and perpendicular to the loading direction provides four-way shape memory behaviour during stress-free thermal cycling after tensile deformation.
Graphical abstract
http://ift.tt/2n9i5jr
Complete Metabolic Response on Interim 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography to Predict Long-Term Survival in Patients with Breast Cancer Undergoing Neoadjuvant Chemotherapy
Background.
This study aims to investigate the prognostic role of complete metabolic response (CMR) on interim 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in patients with breast cancer (BC) receiving neoadjuvant chemotherapy (NAC) according to tumor subtypes and PET timing.
Patients and Methods.Eighty-six consecutive patients with stage II/III BC who received PET/CT during or following NAC were included. Time-dependent receiver operating characteristic analysis and Kaplan-Meier analysis were used to determine correlation between metabolic parameters and survival outcomes.
Results.The median follow-up duration was 71 months. Maximum standardized uptake value (SUVmax) on an interim PET/CT independently correlated with survival by multivariate analysis (overall survival [OS]: hazard ratio: 1.139, 95% confidence interval: 1.058–1.226, p = .001). By taking PET timing into account, best association of SUVmax with survival was obtained on PET after two to three cycles of NAC (area under the curve [AUC]: 0.941 at 1 year after initiation of NAC) and PET after four to five (AUC: 0.871 at 4 years), while PET after six to eight cycles of NAC had less prognostic value. CMR was obtained in 62% of patients (23/37) with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2–) BC, in 48% (12/25) triple-negative BC (TNBC), and in 75% (18/24) HER2-positive (HER2+) tumors. Patients with CMR on an early-mid PET had 5-year OS rates of 92% for ER+/HER2– tumors and 80% for TNBC, respectively. Among HER2+ subtype, 89% patients (16/18) with CMR had no relapse.
Conclusion.CMR indicated a significantly better outcome in BC and may serve as a favorable imaging prognosticator. The Oncologist 2017;22:1–9
Implications for Practice: This study shows a significantly better outcome for breast cancer (BC) patients who achieved complete metabolic response (CMR) on 18F-fluorodeoxyglucose emission tomography/computed tomography (PET/CT) during neoadjuvant chemotherapy, especially for hormone receptor-positive tumors and triple negative BC. Moreover, PET/CT performed during an early- or mid-course neoadjuvant therapy is more predictive for long-term survival outcome than a late PET/CT. These findings support that CMR may serve as a favorable imaging prognosticator for BC and has potential for application to daily clinical practice.
http://ift.tt/2oGnifI
Silk I and Silk II Studied by Fast Scanning Calorimetry
Publication date: Available online 5 April 2017
Source:Acta Biomaterialia
Author(s): Peggy Cebe, Benjamin P. Partlow, David L. Kaplan, Andreas Wurm, Evgeny Zhuravlev, Christoph Schick
Using fast scanning calorimetry (FSC), we investigated the glass transition and crystal melting of samples of B. mori silk fibroin containing Silk I and/or Silk II crystals. Due to the very short residence times at high temperatures during such measurements, thermal decomposition of silk protein can be significantly suppressed. FSC was performed at 2000 K/s using the Mettler Flash DSC1 on fibroin films with masses around 130-270 ng. Films were prepared with different crystalline fractions (ranging from 0.26 to 0.50) and with different crystal structures (Silk I, Silk II, or mixed) by varying the processing conditions. These included water annealing at different temperatures, exposure to 50% MeOH in water, or autoclaving. The resulting crystal structure was examined using wide angle X-ray scattering. Degree of crystallinity was evaluated from Fourier transform infrared (FTIR) spectroscopy and from analysis of the heat capacity increment at the glass transition temperature. Silk fibroin films prepared by water annealing at 25 °C were the least crystalline and had Silk I structure. FTIR and FSC studies showed that films prepared by autoclaving or 50% MeOH exposure were the most crystalline and had Silk II structure. Intermediate crystalline fraction and mixed Silk I/Silk II structures were found in films prepared by water annealing at 37 °C. FSC results indicate that Silk II crystals exhibit endotherms of narrower width and have higher mean melting temperature Tm(II) = 351 ± 2.6 °C, compared to Silk I crystals which melt at Tm(I) = 292 ± 3.8 °C. Films containing mixed Silk I/Silk II structure showed two clearly separated endothermic peaks. Evidence suggests that the two types of crystals melt separately and do not thermally interconvert on the extremely short time scale (0.065 s between onset and end of melting) of the FSC experiment.Statement of significanceSilkworm silk is a naturally occurring biomaterial. The fibroin component of silk forms two types of crystals. Silk properties depend upon the amount and type of crystals, and their stability. One measure of stability is crystal melting temperature. Crystals which are more stable have a higher melting temperature. Until now, it has been challenging to study thermal behavior of silk crystals because they degrade at high temperature. To avoid degradation, and study the melting properties of silk biomaterial, we heated silk at a very fast rate of 2000 K/s using a special calorimeter. We have shown that the two crystal types have very different melting temperatures, indicating that one crystal type is much more stable than the other.
Graphical abstract
http://ift.tt/2o7QU8a
Cancer chemopreventive activity of compounds isolated from Waltheria indica
Publication date: 5 May 2017
Source:Journal of Ethnopharmacology, Volume 203
Author(s): Aymeric Monteillier, Sylvian Cretton, Olivier Ciclet, Laurence Marcourt, Samad Nejad Ebrahimi, Philippe Christen, Muriel Cuendet
Ethnopharmacological relevanceWaltheria indica L. is traditionally used in several countries against inflammatory related diseases and cancer, mainly as a decoction of the aerial parts.Aim of the studyThe transcription factor NF-κB is known to induce tumor promotion and progression and is considered a major player in inflammation-driven cancers. Therefore, inhibitors of this pathway possess cancer chemopreventive and chemotherapeutic activities. This study aimed first to confirm the use of Waltheria indica as a traditional anti-inflammatory remedy by assessing the NF-κB inhibitory activity and then to identify the major bioactive compounds. The isolated compounds were also tested for their QR inducing property, a complementary strategy in cancer chemoprevention able to target tumor initiation. Finally, the relevance of in vitro results was examined by investigating the occurrence of the active compounds in traditional preparations.Materials and methodsCompounds were isolated from the dichloromethane extract of the aerial parts using flash chromatography and semi-preparative HPLC. NF-κB inhibitory activity of pure compounds from Waltheria indica was assessed using a luciferase reporter assay in HEK293 cells. Their QR inducing activity was also assessed in Hepa1c1c7 cells.ResultsTwenty-nine compounds, of which 5 are new, were obtained from the dichloromethane extract and tested for their cancer chemoprevention activity. Eleven compounds inhibited NF-κB and/or induced QR in the low to mid µM range. Chrysosplenol E (20) was active in both tests. Two of the most potent NF-κB inhibitors, waltherione A (4) and waltherione C (5), as well as 20 were found in the traditional decoction, in which 4 and 5 were major compounds.ConclusionThe presence of potent NF-κB inhibitors and QR inducing compounds in the decoction of the aerial parts of Waltheria indica supports its traditional use in inflammatory-related diseases and cancer chemoprevention.
Graphical abstract
http://ift.tt/2nIaPr3
IFC (Journal of Ethnopharmacology)
Publication date: 18 April 2017
Source:Journal of Ethnopharmacology, Volume 202
http://ift.tt/2oA2bzb
Prolactin receptors in Rip-cre cells, but not in AgRP neurons, are involved in energy homeostasis
Abstract
Among its many functions, prolactin has been implicated in energy homeostasis, particularly during pregnancy and lactation. The arcuate nucleus is a key site in the regulation of energy balance. The aim of this study was to examine whether arcuate nucleus neuronal populations involved in energy homeostasis are prolactin responsive and if they can mediate the effects of prolactin on energy homeostasis. To determine if Agrp neurons or Rip-Cre neurons are prolactin responsive, transgenic mice expressing the reporter td-tomato in Agrp neurons (td-tomato/AgRP-Cre) or Rip-Cre neurons (td-tomato/Rip-Cre) were treated with prolactin and perfused 45 minutes later. Brains were processed for double-labeled immunohistochemistry for pSTAT5, a marker of prolactin-induced intracellular signaling, and td-tomato. In addition, Agrp-Cre mice and Rip-Cre mice were crossed with mice in which the prolactin receptor gene (Prlr) was flanked with LoxP sites (Prlrlox/lox mice). The Prlrlox/lox construct was designed such that Cre-mediated recombination resulted in deletion of the Prlr and expression of GFP in its place. In td-tomato/Rip-Cre mice, prolactin-induced pSTAT5 was co-localized with td-tomato, indicating that there is a subpopulation of Rip-Cre neurons in the arcuate nucleus that respond to prolactin. Furthermore, mice with a specific deletion of Prlr in Rip-Cre neurons had lower body weights, increased oxygen consumption, increased running wheel activity, and numerous cells in the arcuate nucleus had positive GFP staining indicating deletion of Prlr from Rip-Cre neurons. In contrast, no co-localization of td-tomato and pSTAT5 was observed in td-tomato/Agrp-Cre mice following prolactin treatment. Moreover, Prlrlox/lox/Agrp-Cre mice had no positive GFP staining in the arcuate nucleus and did not differ in body weight compared to litter mate controls. Overall these results indicate that Rip-Cre neurons in the arcuate nucleus are responsive to prolactin and may play a role in the orexigenic effects of prolactin, while prolactin does not directly affect Agrp neurons.
This article is protected by copyright. All rights reserved.
http://ift.tt/2ozPMex
A Tunable Diffusion-Consumption Mechanism of Cytokine Propagation Enables Plasticity in Cell-to-Cell Communication in the Immune System
Publication date: Available online 4 April 2017
Source:Immunity
Author(s): Alon Oyler-Yaniv, Jennifer Oyler-Yaniv, Benjamin M. Whitlock, Zhiduo Liu, Ronald N. Germain, Morgan Huse, Grégoire Altan-Bonnet, Oleg Krichevsky
Immune cells communicate by exchanging cytokines to achieve a context-appropriate response, but the distances over which such communication happens are not known. Here, we used theoretical considerations and experimental models of immune responses in vitro and in vivo to quantify the spatial extent of cytokine communications in dense tissues. We established that competition between cytokine diffusion and consumption generated spatial niches of high cytokine concentrations with sharp boundaries. The size of these self-assembled niches scaled with the density of cytokine-consuming cells, a parameter that gets tuned during immune responses. In vivo, we measured interactions on length scales of 80–120 μm, which resulted in a high degree of cell-to-cell variance in cytokine exposure. Such heterogeneous distributions of cytokines were a source of non-genetic cell-to-cell variability that is often overlooked in single-cell studies. Our findings thus provide a basis for understanding variability in the patterning of immune responses by diffusible factors.
Graphical abstract
Teaser
Cytokine-mediated communication allows immune cells to achieve a context-appropriate response, but the distance over which this communication happens is unclear. Oyler-Yaniv et al. (2017) show that a simple diffusion-consumption mechanism quantitatively describes the spatial spread of cytokines in vivo and results in localized niches of high cytokine concentrations that contribute to cell-to-cell variability.http://ift.tt/2oAWxMB
Iodide Handling Disorders (NIS, TPO, TG, IYD)
Publication date: Available online 4 April 2017
Source:Best Practice & Research Clinical Endocrinology & Metabolism
Author(s): Héctor M. Targovnik, Cintia E. Citterio, Carina M. Rivolta
Iodide Handling Disorders lead to defects of the biosynthesis of thyroid hormones (thyroid dyshormonogenesis, TD) and thereafter congenital hypothyroidism (CH), the most common endocrine disease characterized by low levels of circulating thyroid hormones. The prevalence of CH is 1 in 2000 – 3000 live births. Prevention of CH is based on prenatal diagnosis, carrier identification, and genetic counseling. In neonates a complete diagnosis of TD should include clinical examination, biochemical thyroid tests, thyroid ultrasound, radioiodine or technetium scintigraphy and perchlorate discharge test (PDT).Biosynthesis of thyroid hormones requires the presence of iodide, thyroid peroxidase (TPO), a supply of hydrogen peroxide (DUOX system), an iodine acceptor protein, thyroglobulin (TG), and the rescue and recycling of iodide by the action of iodotyrosine deiodinase or dehalogenase 1 (IYD or DEHAL1). The iodide transport is a two-step process involving transporters located either in the basolateral or apical membranes, sodium iodide symporter (NIS) and pendrin (PDS), respectively. TD has been linked to mutations in the solute carrier family 5, member 5 transporter (SLC5A5, encoding NIS), solute carrier family 26, member 4 transporter (SLC26A4, encoding PDS), TPO, DUOX2, DUOXA2, TG and IYD genes. These mutations produce a heterogeneous spectrum of CH, with an autosomal recessive inheritance. Thereafter, the patients are usually homozygous or compound heterozygous for the gene mutations and the parents, carriers of one mutation. In the last two decades, considerable progress has been made in identifying the genetic and molecular causes of TD. Recent advances in DNA sequencing technology allow the massive screening and facilitate the studies of phenotype variability. In this article we included the most recent data related to disorders caused by mutations in NIS, TPO, TG and IYD.
http://ift.tt/2oA2qdF
The Motor-Cognitive Model of Motor Imagery: Evidence From Timing Errors in Simulated Reaching and Grasping.
http://ift.tt/2nVvCbB
The Magical Number One-on-Square-Root-Two: The Double-Target Detection Deficit in Brief Visual Displays.
http://ift.tt/2ozTfto
Avoiding the Conflict: Metacognitive Awareness Drives the Selection of Low-Demand Contexts.
http://ift.tt/2nVA7mI
The Role of Allograph Representations in Font-Invariant Letter Identification.
http://ift.tt/2ozPkg7
Domain-General Biases in Spatial Localization: Evidence Against a Distorted Body Model Hypothesis.
http://ift.tt/2nVgJGb
Conceptual Biases Explain Distortion Differences Between Hand and Objects in Localization Tasks.
http://ift.tt/2ozLmnR
Co-Representation of Others' Task Constraints in Joint Action.
http://ift.tt/2nVtdxH
Dual-Target Cost in Visual Search for Multiple Unfamiliar Faces.
http://ift.tt/2ozOwbi
Attention Mediates the Flexible Allocation of Visual Working Memory Resources.
http://ift.tt/2nVlqji
Cognitive-Behavioral High Parental Involvement Treatments for Pediatric Obsessive-Compulsive Disorder: A Meta-analysis
Source:Journal of Anxiety Disorders
Author(s): Marina Iniesta-Sepúlveda, Ana I. Rosa-Alcázar, Julio Sánchez-Meca, Ángel Rosa-Alcázar, José L. Parada-Navas
http://ift.tt/2ozMw2L
Clinical laser treatment of toenail onychomycoses
Abstract
Onychomycoses are fungal infections of the fingernails or toenails having a prevalence of 3% among adults and accounts for 50% of nail infections. It is caused by dermatophytes, non-dermatophyte filamentous fungi, and yeasts. Compressions and microtraumas significantly contribute to onychomycosis. Laser and photodynamic therapies are being proposed to treat onychomycosis. Laser light (1064 nm) was used to treat onychomycosis in 156 affected toenails. Patients were clinically followed up for 9 months after treatment. Microbiological detection of fungal presence in lesions was accomplished. A total of 116 samples allowed the isolation of at least a fungus. Most of nails were affected in more than two thirds surface (some of them in the full surface). In 85% of cases, after 18 months of the onset of treatment, culture turned negative. After 3 months months, only five patients were completely symptom-free with negative culture. In 25 patients, only after 6 months, the absence of symptoms was achieved and the cultures negativized; in 29 patients, 9 months were required. No noticeable adverse effects were reported. This study reinforces previous works suggesting the applicability of laser therapies to treat toenail onychomycosis.
http://ift.tt/2nGqO9n
Training spatial-simultaneous working memory in individuals with Down syndrome
Source:Research in Developmental Disabilities, Volume 64
Author(s): Silvia Lanfranchi, Francesca Pulina, Barbara Carretti, Irene C. Mammarella
Recent studies have suggested that the spatial-simultaneous component of working memory (WM), which is involved when stimuli are presented simultaneously, is selectively impaired in individuals with Down syndrome (DS).The main objective of the present study was to examine whether WM performance can be enhanced in individuals with DS by analyzing the immediate and maintenance effects of a training program. For this purpose, 61 individuals with DS were randomly assigned to three groups: one trained on simultaneous components of visuospatial WM; one serving as an active control group, that completed activities on vocabulary; and one serving as a passive control group, that only attended the pre- and post-test and follow-up assessments. The efficacy of the training was analyzed in terms of specific (spatial-simultaneous WM tasks), near transfer (spatial-sequential and verbal WM tasks), far transfer (spatial abilities, everyday competences), and maintenance effects (with a follow-up at 1 month). The results showed an overall significant effect on the WM on the group receiving the training. The benefit was generally specific, however, with some transfer to other WM tasks, but only in the immediate (post-test) assessment.
http://ift.tt/2oXNphI
Dictating genomic destiny: Epigenetic regulation of pancreatic neuroendocrine tumours
Source:Molecular and Cellular Endocrinology
Author(s): Justin S. Gundara, Karim Jamal, Tom Kurzawinski
Pancreatic neuroendocrine tumours are a diverse group of neoplasms with an increasingly well-defined genomic basis. Despite this, much of what drives this disease is still unknown and epigenetic influences represent the next tier of gene, and hence disease modifiers that are of unquestionable importance. Moreover, they are of arguably more significance than the genes themselves given their malleable nature and potential to be exploited for not only diagnosis and prognosis, but also therapy. This review summarises what is known regarding the key epigenetic modifiers of disease through the domains of diagnosis, prognosis and treatment.
http://ift.tt/2n8Xs7h
Brown Fat-Derived Exosomes: Small Vesicles with Big Impact
Publication date: 4 April 2017
Source:Cell Metabolism, Volume 25, Issue 4
Author(s): Yong Chen, Alexander Pfeifer
Adipose tissue (AT) not only stores energy, but also secretes hormones and releases small vesicles known as exosomes. Thomou et al. (2017) now show that exosomes secreted by brown fat carry miRNAs that regulate the liver. Thus, AT exosomes might have therapeutic and diagnostic relevance for metabolic disorders.
Teaser
Adipose tissue (AT) not only stores energy, but also secretes hormones and releases small vesicles known as exosomes. Thomou et al. (2017) now show that exosomes secreted by brown fat carry miRNAs that regulate the liver. Thus, AT exosomes might have therapeutic and diagnostic relevance for metabolic disorders.http://ift.tt/2oXBjoT
Now UCP(rotein), Now You Don’t: UCP1 Is Not Mandatory for Thermogenesis
Publication date: 4 April 2017
Source:Cell Metabolism, Volume 25, Issue 4
Author(s): Ildiko Szabo, Mario Zoratti
Adipocyte-targeted therapies could potentially combat obesity and metabolic disorders; however, our understanding of adipogenesis and the characterization of the various adipose tissues are incomplete. In this issue, Bertholet et al. (2017) report the existence of two types of heat-producing beige-like adipocytes, those with and those without the mitochondrial uncoupling protein 1 (UCP1).
Teaser
Adipocyte-targeted therapies could potentially combat obesity and metabolic disorders; however, our understanding of adipogenesis and the characterization of the various adipose tissues are incomplete. In this issue, Bertholet et al. report the existence of two types of heat-producing beige-like adipocytes, those with and those without the mitochondrial uncoupling protein 1 (UCP1).http://ift.tt/2oztRUz
A Novel Protective Role for FXR against Inflammasome Activation and Endotoxemia
Publication date: 4 April 2017
Source:Cell Metabolism, Volume 25, Issue 4
Author(s): Oihane Garcia-Irigoyen, Antonio Moschetta
During conditions of impaired bile flow (cholestasis), increased serum bile acids (BAs) are prognostic markers of sepsis. In this issue, Hao et al. (2017) show that the BA receptor FXR binds NLRP3 inflammasome in macrophages and inhibits activation of inflammasome components, thus reducing endotoxemia in cholestasis.
Teaser
During conditions of impaired bile flow (cholestasis), increased serum bile acids (BAs) are prognostic markers of sepsis. In this issue, Hao et al. (2017) show that the BA receptor FXR binds NLRP3 inflammasome in macrophages and inhibits activation of inflammasome components, thus reducing endotoxemia in cholestasis.http://ift.tt/2oXssUi
The Enigma of the Respiratory Chain Supercomplex
Publication date: 4 April 2017
Source:Cell Metabolism, Volume 25, Issue 4
Author(s): Dusanka Milenkovic, James N. Blaza, Nils-Göran Larsson, Judy Hirst
Respiratory chain dysfunction plays an important role in human disease and aging. It is now well established that the individual respiratory complexes can be organized into supercomplexes, and structures for these macromolecular assemblies, determined by electron cryo-microscopy, have been described recently. Nevertheless, the reason why supercomplexes exist remains an enigma. The widely held view that they enhance catalysis by channeling substrates is challenged by both structural and biophysical information. Here, we evaluate and discuss data and hypotheses on the structures, roles, and assembly of respiratory-chain supercomplexes and propose a future research agenda to address unanswered questions.
Teaser
Milenkovic et al. review the present understanding of the structure, function, and assembly of mitochondrial respiratory chain supercomplexes. Only weak molecular interactions between the individual respiratory chain complexes hold supercomplexes together and their function remains enigmatic because structural data do not support a role in substrate channeling during electron transport.http://ift.tt/2ozrrWm
GPCR-Mediated Signaling of Metabolites
Publication date: 4 April 2017
Source:Cell Metabolism, Volume 25, Issue 4
Author(s): Anna Sofie Husted, Mette Trauelsen, Olga Rudenko, Siv A. Hjorth, Thue W. Schwartz
In addition to their bioenergetic intracellular function, several classical metabolites act as extracellular signaling molecules activating cell-surface G-protein-coupled receptors (GPCRs), similar to hormones and neurotransmitters. "Signaling metabolites" generated from nutrients or by gut microbiota target primarily enteroendocrine, neuronal, and immune cells in the lamina propria of the gut mucosa and the liver and, through these tissues, the rest of the body. In contrast, metabolites from the intermediary metabolism act mainly as metabolic stress-induced autocrine and paracrine signals in adipose tissue, the liver, and the endocrine pancreas. Importantly, distinct metabolite GPCRs act as efficient pro- and anti-inflammatory regulators of key immune cells, and signaling metabolites may thus function as important drivers of the low-grade inflammation associated with insulin resistance and obesity. The concept of key metabolites as ligands for specific GPCRs has broadened our understanding of metabolic signaling significantly and provides a number of novel potential drug targets.
Graphical abstract
Teaser
Husted et al. describe how metabolites act not only as energy sources and building blocks, but as extracellular signaling molecules activating cell-surface GPCRs to control metabolism. "Signaling metabolites" are derived from nutrients, generated by gut microbiota, or function locally as metabolic stress signals and drivers of low-grade inflammation.http://ift.tt/2oXoqv2
Pancreas and Not Gut Mediates the GLP-1-Induced Glucoincretin Effect
Publication date: 4 April 2017
Source:Cell Metabolism, Volume 25, Issue 4
Author(s): Joel F. Habener, Violeta Stanojevic
The gut is believed to be the source of GLP-1 that augments insulin secretion in response to oral nutrients. In this issue of Cell Metabolism, Chambers et al. (2017) shift the paradigm by finding that GLP-1 produced within the islets of the pancreas, and not the gut, is responsible for the incretin effect in mice.
Teaser
The gut is believed to be the source of GLP-1 that augments insulin secretion in response to oral nutrients. In this issue of Cell Metabolism, Chambers et al. (2017) shift the paradigm by finding that GLP-1 produced within the islets of the pancreas, and not the gut, is responsible for the incretin effect in mice.http://ift.tt/2oXIehL
Imbalanced Insulin Actions in Obesity and Type 2 Diabetes: Key Mouse Models of Insulin Signaling Pathway
Publication date: 4 April 2017
Source:Cell Metabolism, Volume 25, Issue 4
Author(s): Tetsuya Kubota, Naoto Kubota, Takashi Kadowaki
Since the discovery of the tyrosine kinase activity of the insulin receptor (IR), researchers have been engaged in intensive efforts to resolve physiological functions of IR and its major downstream targets, insulin receptor substrate 1 (Irs1) and Irs2. Studies conducted using systemic and tissue-specific gene-knockout mice of IR, Irs1, and Irs2 have revealed the physiological roles of these molecules in each tissue and interactions among multiple tissues. In obesity and type 2 diabetes, selective downregulation of Irs2 and its downstream actions to cause reduced insulin actions was associated with increased insulin actions through Irs1 in variety tissues. Thus, we propose the novel concept of "organ- and pathway-specific imbalanced insulin action" in obesity and type 2 diabetes, which includes and extends "selective insulin resistance." This Review focuses on recent progress in understanding insulin signaling and insulin resistance using key mouse models for elucidating pathophysiology of human obesity and type 2 diabetes.
Teaser
The application of mouse models has provided new mechanistic insights into the insulin signaling pathways. Kubota et al. review the physiology of insulin signaling and pathophysiology of obesity and type 2 diabetes, proposing the concept of "organ- and pathway-specific imbalanced insulin actions."http://ift.tt/2oztbyB
Mitochondrial Patch Clamp of Beige Adipocytes Reveals UCP1-Positive and UCP1-Negative Cells Both Exhibiting Futile Creatine Cycling
Publication date: 4 April 2017
Source:Cell Metabolism, Volume 25, Issue 4
Author(s): Ambre M. Bertholet, Lawrence Kazak, Edward T. Chouchani, Marta G. Bogaczyńska, Ishan Paranjpe, Gabrielle L. Wainwright, Alexandre Bétourné, Shingo Kajimura, Bruce M. Spiegelman, Yuriy Kirichok
Cold and other environmental factors induce "browning" of white fat depots—development of beige adipocytes with morphological and functional resemblance to brown fat. Similar to brown fat, beige adipocytes are assumed to express mitochondrial uncoupling protein 1 (UCP1) and are thermogenic due to the UCP1-mediated H+ leak across the inner mitochondrial membrane. However, this assumption has never been tested directly. Herein we patch clamped the inner mitochondrial membrane of beige and brown fat to provide a direct comparison of their thermogenic H+ leak (IH). All inguinal beige adipocytes had robust UCP1-dependent IH comparable to brown fat, but it was about three times less sensitive to purine nucleotide inhibition. Strikingly, only ∼15% of epididymal beige adipocytes had IH, while in the rest UCP1-dependent IH was undetectable. Despite the absence of UCP1 in the majority of epididymal beige adipocytes, these cells employ prominent creatine cycling as a UCP1-independent thermogenic mechanism.
Graphical abstract
Teaser
Using patch-clamping and bioenergetics analyses of isolated mitochondria, Bertholet et al. investigated the thermogenic mechanisms of beige fat and identified two distinct types of beige adipocytes: UCP1 positive and UCP1 negative. Beige adipocytes of abdominal fat are mostly UCP1 negative but possess thermogenic capacity associated with a futile creatine cycle.http://ift.tt/2oXs9IS
A Class of Reactive Acyl-CoA Species Reveals the Non-enzymatic Origins of Protein Acylation
Publication date: 4 April 2017
Source:Cell Metabolism, Volume 25, Issue 4
Author(s): Gregory R. Wagner, Dhaval P. Bhatt, Thomas M. O'Connell, J. Will Thompson, Laura G. Dubois, Donald S. Backos, Hao Yang, Grant A. Mitchell, Olga R. Ilkayeva, Robert D. Stevens, Paul A. Grimsrud, Matthew D. Hirschey
The mechanisms underlying the formation of acyl protein modifications remain poorly understood. By investigating the reactivity of endogenous acyl-CoA metabolites, we found a class of acyl-CoAs that undergo intramolecular catalysis to form reactive intermediates that non-enzymatically modify proteins. Based on this mechanism, we predicted, validated, and characterized a protein modification: 3-hydroxy-3-methylglutaryl(HMG)-lysine. In a model of altered HMG-CoA metabolism, we found evidence of two additional protein modifications: 3-methylglutaconyl(MGc)-lysine and 3-methylglutaryl(MG)-lysine. Using quantitative proteomics, we compared the "acylomes" of two reactive acyl-CoA species, namely HMG-CoA and glutaryl-CoA, which are generated in different pathways. We found proteins that are uniquely modified by each reactive metabolite, as well as common proteins and pathways. We identified the tricarboxylic acid cycle as a pathway commonly regulated by acylation and validated malate dehydrogenase as a key target. These data uncover a fundamental relationship between reactive acyl-CoA species and proteins and define a new regulatory paradigm in metabolism.
Graphical abstract
Teaser
Wagner et al. discover a class of negatively charged acyl-CoA species that are highly reactive metabolites capable of non-enzymatic acylation on a wide range of proteins. They identify the TCA cycle as a pathway commonly regulated by acylation and validate malate dehydrogenase as a key target.http://ift.tt/2oXJstp
SIRT4 Is a Lysine Deacylase that Controls Leucine Metabolism and Insulin Secretion
Publication date: 4 April 2017
Source:Cell Metabolism, Volume 25, Issue 4
Author(s): Kristin A. Anderson, Frank K. Huynh, Kelsey Fisher-Wellman, J. Darren Stuart, Brett S. Peterson, Jonathan D. Douros, Gregory R. Wagner, J. Will Thompson, Andreas S. Madsen, Michelle F. Green, R. Michael Sivley, Olga R. Ilkayeva, Robert D. Stevens, Donald S. Backos, John A. Capra, Christian A. Olsen, Jonathan E. Campbell, Deborah M. Muoio, Paul A. Grimsrud, Matthew D. Hirschey
Sirtuins are NAD+-dependent protein deacylases that regulate several aspects of metabolism and aging. In contrast to the other mammalian sirtuins, the primary enzymatic activity of mitochondrial sirtuin 4 (SIRT4) and its overall role in metabolic control have remained enigmatic. Using a combination of phylogenetics, structural biology, and enzymology, we show that SIRT4 removes three acyl moieties from lysine residues: methylglutaryl (MG)-, hydroxymethylglutaryl (HMG)-, and 3-methylglutaconyl (MGc)-lysine. The metabolites leading to these post-translational modifications are intermediates in leucine oxidation, and we show a primary role for SIRT4 in controlling this pathway in mice. Furthermore, we find that dysregulated leucine metabolism in SIRT4KO mice leads to elevated basal and stimulated insulin secretion, which progressively develops into glucose intolerance and insulin resistance. These findings identify a robust enzymatic activity for SIRT4, uncover a mechanism controlling branched-chain amino acid flux, and position SIRT4 as a crucial player maintaining insulin secretion and glucose homeostasis during aging.
Graphical abstract
Teaser
Anderson and Huynh et al. show that SIRT4 is a protein deacylase targeting lysine modifications derived from reactive acyl species produced from leucine catabolism. Mice lacking SIRT4 have dysregulated leucine metabolism leading to chronically elevated insulin secretion and accelerated age-induced insulin resistance.http://ift.tt/2oXoATh
Farnesoid X Receptor Regulation of the NLRP3 Inflammasome Underlies Cholestasis-Associated Sepsis
Publication date: 4 April 2017
Source:Cell Metabolism, Volume 25, Issue 4
Author(s): Haiping Hao, Lijuan Cao, Changtao Jiang, Yuan Che, Songyang Zhang, Shogo Takahashi, Guangji Wang, Frank J. Gonzalez
Cholestasis is a common complication of sepsis, and the increased plasma levels of bile acids are predictive of sepsis-associated mortality. However, the exact mechanism by which cholestasis aggravates sepsis development remains elusive. Here, we show that bile acids are danger-associated molecular patterns (DAMPs) that can activate both signal 1 and 2 of the NLRP3 inflammasome in inflammatory macrophages. Mechanistically, bile acids induce a prolonged calcium influx and activate the NLRP3 inflammasome synergistically with ATP. Experimental cholestasis sensitizes, while cholestyramine, a bile acid sequestrant, protects mice from LPS-induced sepsis. FXR negatively regulates the NLRP3 inflammasome via physical interaction with NLRP3 and caspase 1. Fxr-null mice are more sensitive, while FXR-overexpressing mice are more resistant, to endoxemia shock. These findings suggest that bile acids and FXR play pivotal roles in sepsis via controlling the NLRP3 inflammasome, and that targeting FXR may represent a therapeutic strategy for cholestasis-associated sepsis.
Graphical abstract
Teaser
Cholestasis is associated with high mortality due to sepsis. Hao et al. dissect how cholestasis potentiates septic shock progression and reveal that bile acids act as DAMPs activating both signal 1 and 2 of the NLRP3 inflammasome in inflammatory macrophages. They further show that FXR negatively regulates NLRP3 activation.http://ift.tt/2oXNKki
Targeting ABL-IRE1α Signaling Spares ER-Stressed Pancreatic β Cells to Reverse Autoimmune Diabetes
Publication date: 4 April 2017
Source:Cell Metabolism, Volume 25, Issue 4
Author(s): Shuhei Morita, S. Armando Villalta, Hannah C. Feldman, Ames C. Register, Wendy Rosenthal, Ingeborg T. Hoffmann-Petersen, Morvarid Mehdizadeh, Rajarshi Ghosh, Likun Wang, Kevin Colon-Negron, Rosa Meza-Acevedo, Bradley J. Backes, Dustin J. Maly, Jeffrey A. Bluestone, Feroz R. Papa
In cells experiencing unrelieved endoplasmic reticulum (ER) stress, the ER transmembrane kinase/endoribonuclease (RNase)—IRE1α—endonucleolytically degrades ER-localized mRNAs to promote apoptosis. Here we find that the ABL family of tyrosine kinases rheostatically enhances IRE1α's enzymatic activities, thereby potentiating ER stress-induced apoptosis. During ER stress, cytosolic ABL kinases localize to the ER membrane, where they bind, scaffold, and hyperactivate IRE1α's RNase. Imatinib—an anti-cancer tyrosine kinase inhibitor—antagonizes the ABL-IRE1α interaction, blunts IRE1α RNase hyperactivity, reduces pancreatic β cell apoptosis, and reverses type 1 diabetes (T1D) in the non-obese diabetic (NOD) mouse model. A mono-selective kinase inhibitor that allosterically attenuates IRE1α's RNase—KIRA8—also efficaciously reverses established diabetes in NOD mice by sparing β cells and preserving their physiological function. Our data support a model wherein ER-stressed β cells contribute to their own demise during T1D pathogenesis and implicate the ABL-IRE1α axis as a drug target for the treatment of an autoimmune disease.
Graphical abstract
Teaser
Morita et al. show that the non-receptor ABL tyrosine kinases enhance the enzymatic activities of the ER transmembrane kinase/endoribonuclease, IRE1α, thereby potentiating ER stress-induced apoptosis. Targeting the ABL-IRE1α pathway with imatinib or selective IRE1α kinase inhibitors reverses autoimmune diabetes in mice.http://ift.tt/2oXNKRk
β Cell Aging Markers Have Heterogeneous Distribution and Are Induced by Insulin Resistance
Publication date: 4 April 2017
Source:Cell Metabolism, Volume 25, Issue 4
Author(s): Cristina Aguayo-Mazzucato, Mark van Haaren, Magdalena Mruk, Terence B. Lee, Caitlin Crawford, Jennifer Hollister-Lock, Brooke A. Sullivan, James W. Johnson, Aref Ebrahimi, Jonathan M. Dreyfuss, Jan Van Deursen, Gordon C. Weir, Susan Bonner-Weir
We hypothesized that the known heterogeneity of pancreatic β cells was due to subpopulations of β cells at different stages of their life cycle with different functional capacities and that further changes occur with metabolic stress and aging. We identified new markers of aging in β cells, including IGF1R. In β cells IGF1R expression correlated with age, dysfunction, and expression of known age markers p16ink4a, p53BP1, and senescence-associated β-galactosidase. The new markers showed striking heterogeneity both within and between islets in both mouse and human pancreas. Acute induction of insulin resistance with an insulin receptor antagonist or chronic ER stress resulted in increased expression of aging markers, providing insight into how metabolic stress might accelerate dysfunction and decline of β cells. These novel findings about β cell and islet heterogeneity, and how they change with age, open up an entirely new set of questions about the pathogenesis of type 2 diabetes.
Graphical abstract
Teaser
Aguayo-Mazzucato et al. show that the heterogeneity of pancreatic β cells is likely due to individual β cells at their respective life cycle stage expressing different markers and functional characteristics. Both age and environmental factors, including metabolic stress, can shift the composition of the β cell population contributing to diabetes.http://ift.tt/2oXBgJJ
Virgin Beta Cells Persist throughout Life at a Neogenic Niche within Pancreatic Islets
Publication date: 4 April 2017
Source:Cell Metabolism, Volume 25, Issue 4
Author(s): Talitha van der Meulen, Alex M. Mawla, Michael R. DiGruccio, Michael W. Adams, Vera Nies, Sophie Dólleman, Siming Liu, Amanda M. Ackermann, Elena Cáceres, Anna E. Hunter, Klaus H. Kaestner, Cynthia J. Donaldson, Mark O. Huising
Postnatal maintenance or regeneration of pancreatic beta cells is considered to occur exclusively via the replication of existing beta cells, but clinically meaningful restoration of human beta cell mass by proliferation has never been achieved. We discovered a population of immature beta cells that is present throughout life and forms from non-beta precursors at a specialized micro-environment or "neogenic niche" at the islet periphery. These cells express insulin, but lack other key beta cell markers, and are transcriptionally immature, incapable of sensing glucose, and unable to support calcium influx. They constitute an intermediate stage in the transdifferentiation of alpha cells to cells that are functionally indistinguishable from conventional beta cells. We thus identified a lifelong source of new beta cells at a specialized site within healthy islets. By comparing co-existing immature and mature beta cells within healthy islets, we stand to learn how to mature insulin-expressing cells into functional beta cells.
Graphical abstract
Teaser
Van der Meulen et al. identify a population of immature beta cells originating by transdifferentiation of alpha cells at a pancreatic neogenic niche. Immature beta cells are also present in human islets. They propose targeting this ongoing plasticity within the neogenic niche for beta cell regeneration.http://ift.tt/2oXIgGs
FGF21 Regulates Metabolism Through Adipose-Dependent and -Independent Mechanisms
Publication date: 4 April 2017
Source:Cell Metabolism, Volume 25, Issue 4
Author(s): Lucas D. BonDurant, Magdalene Ameka, Meghan C. Naber, Kathleen R. Markan, Sharon O. Idiga, Michael R. Acevedo, Susan A. Walsh, David M. Ornitz, Matthew J. Potthoff
FGF21 is an endocrine hormone that regulates energy homeostasis and insulin sensitivity. The mechanism of FGF21 action and the tissues responsible for these effects have been controversial, with both adipose tissues and the central nervous system having been identified as the target site mediating FGF21-dependent increases in insulin sensitivity, energy expenditure, and weight loss. Here we show that, while FGF21 signaling to adipose tissue is required for the acute insulin-sensitizing effects of FGF21, FGF21 signaling to adipose tissue is not required for its chronic effects to increase energy expenditure and lower body weight. Also, in contrast to previous studies, we found that adiponectin is dispensable for the metabolic effects of FGF21 in increasing insulin sensitivity and energy expenditure. Instead, FGF21 acutely enhances insulin sensitivity through actions on brown adipose tissue. Our data reveal that the acute and chronic effects of FGF21 can be dissociated through adipose-dependent and -independent mechanisms.
Graphical abstract
Teaser
Pharmacological administration of FGF21 increases insulin sensitivity and promotes weight loss. BonDurant et al. show that FGF21 signaling to adipose tissues is essential for the acute insulin-sensitizing effects of FGF21, but not for its effects on body weight. Importantly, loss of FGF21 signaling specifically to brown adipocytes disrupts FGF21-mediated glucose disposal.http://ift.tt/2oXA891
A Single Adaptable Cochaperone-Scaffold Complex Delivers Nascent Iron-Sulfur Clusters to Mammalian Respiratory Chain Complexes I–III
Publication date: 4 April 2017
Source:Cell Metabolism, Volume 25, Issue 4
Author(s): Nunziata Maio, Ki Soon Kim, Anamika Singh, Tracey A. Rouault
The iron-sulfur (Fe-S) cluster of the Rieske protein, UQCRFS1, is essential for Complex III (CIII) activity, though the mechanism for Fe-S cluster transfer has not previously been elucidated. Recent studies have shown that the co-chaperone HSC20, essential for Fe-S cluster biogenesis of SDHB, directly binds LYRM7, formerly described as a chaperone that stabilizes UQCRFS1 prior to its insertion into CIII. Here we report that a transient subcomplex involved in CIII assembly, composed of LYRM7 bound to UQCRFS1, interacts with components of an Fe-S transfer complex, consisting of HSC20, its cognate chaperone HSPA9, and the holo-scaffold ISCU. Binding of HSC20 to the LYR motif of LYRM7 in a pre-assembled UQCRFS1-LYRM7 intermediate in the mitochondrial matrix facilitates Fe-S cluster transfer to UQCRFS1. The five Fe-S cluster subunits of Complex I also interact with HSC20 to acquire their clusters, highlighting the crucial role of HSC20 in the assembly of the mitochondrial respiratory chain.
Graphical abstract
Teaser
Maio et al. identify the crucial role of the co-chaperone HSC20 for the assembly and function of the mitochondrial respiratory chain. Their work also highlights that Complexes I–III share a common molecular mechanism for Fe-S cluster acquisition.http://ift.tt/2oXu93S
Using DNA Methylation Profiling to Evaluate Biological Age and Longevity Interventions
Publication date: 4 April 2017
Source:Cell Metabolism, Volume 25, Issue 4
Author(s): Daniel A. Petkovich, Dmitriy I. Podolskiy, Alexei V. Lobanov, Sang-Goo Lee, Richard A. Miller, Vadim N. Gladyshev
The DNA methylation levels of certain CpG sites are thought to reflect the pace of human aging. Here, we developed a robust predictor of mouse biological age based on 90 CpG sites derived from partial blood DNA methylation profiles. The resulting clock correctly determines the age of mouse cohorts, detects the longevity effects of calorie restriction and gene knockouts, and reports rejuvenation of fibroblast-derived iPSCs. The data show that mammalian DNA methylomes are characterized by CpG sites that may represent the organism's biological age. They are scattered across the genome, they are distinct in human and mouse, and their methylation gradually changes with age. The clock derived from these sites represents a biomarker of aging and can be used to determine the biological age of organisms and evaluate interventions that alter the rate of aging.
Graphical abstract
Teaser
Petkovich et al. developed a precise biomarker of mouse aging based on blood DNA methylation patterns. Their epigenetic clock can estimate the biological age of various mouse models and can be applied to evaluate the effects of genetic, pharmacological, and dietary interventions on average lifespan.http://ift.tt/2oXsqMa
Clock Regulation of Metabolites Reveals Coupling between Transcription and Metabolism
Publication date: 4 April 2017
Source:Cell Metabolism, Volume 25, Issue 4
Author(s): Saikumari Y. Krishnaiah, Gang Wu, Brian J. Altman, Jacqueline Growe, Seth D. Rhoades, Faith Coldren, Anand Venkataraman, Anthony O. Olarerin-George, Lauren J. Francey, Sarmistha Mukherjee, Saiveda Girish, Christopher P. Selby, Sibel Cal, Ubeydullah ER, Bahareh Sianati, Arjun Sengupta, Ron C. Anafi, I. Halil Kavakli, Aziz Sancar, Joseph A. Baur, Chi V. Dang, John B. Hogenesch, Aalim M. Weljie
The intricate connection between the circadian clock and metabolism remains poorly understood. We used high temporal resolution metabolite profiling to explore clock regulation of mouse liver and cell-autonomous metabolism. In liver, ∼50% of metabolites were circadian, with enrichment of nucleotide, amino acid, and methylation pathways. In U2 OS cells, 28% were circadian, including amino acids and NAD biosynthesis metabolites. Eighteen metabolites oscillated in both systems and a subset of these in primary hepatocytes. These 18 metabolites were enriched in methylation and amino acid pathways. To assess clock dependence of these rhythms, we used genetic perturbation. BMAL1 knockdown diminished metabolite rhythms, while CRY1 or CRY2 perturbation generally shortened or lengthened rhythms, respectively. Surprisingly, CRY1 knockdown induced 8 hr rhythms in amino acid, methylation, and vitamin metabolites, decoupling metabolite from transcriptional rhythms, with potential impact on nutrient sensing in vivo. These results provide the first comprehensive views of circadian liver and cell-autonomous metabolism.
Graphical abstract
Teaser
Using high temporal resolution metabolite profiling, Krishnaiah et al. show that over 50% of liver metabolites are circadian, with a significant overlap of cycling metabolites between mouse and human liver, especially those involved in epigenetic regulation. Coupling of metabolite with transcriptional rhythms is regulated by core clock genes.http://ift.tt/2oXujbw
Palatability Can Drive Feeding Independent of AgRP Neurons
Publication date: 4 April 2017
Source:Cell Metabolism, Volume 25, Issue 4
Author(s): Raphaël G.P. Denis, Aurélie Joly-Amado, Emily Webber, Fanny Langlet, Marie Schaeffer, Stéphanie L. Padilla, Céline Cansell, Bénédicte Dehouck, Julien Castel, Anne-Sophie Delbès, Sarah Martinez, Amélie Lacombe, Claude Rouch, Nadim Kassis, Jean-Alain Fehrentz, Jean Martinez, Pascal Verdié, Thomas S. Hnasko, Richard D. Palmiter, Michael J. Krashes, Ali D. Güler, Christophe Magnan, Serge Luquet
http://ift.tt/2oXDpoJ
Not Only Limbs in Atypical Restless Legs Syndrome
Restless legs syndrome (RLS) typically affects the limbs, but the involvement of other body parts has also been reported. In this assay, we critically review all literature reports of atypical RLS cases with unusual localizations. Applying the updated diagnostic criteria of the International Restless Legs Syndrome Study Group (IRLSSG), which also consider symptoms localized outside of the lower limbs, a few of these atypical cases reported in the previous literature resulted in a definitive diagnosis of RLS.
http://ift.tt/2nUV6Wx
Bibliometric Indices of Scientific Journals: Time to overcome the obsession and think beyond the Impact Factor
Publication date: Available online 3 April 2017
Source:Medical Journal Armed Forces India
Author(s): C.K. Ranjan
Journal Impact Factor (JIF) has been widely used for a long time as a proxy marker of journal prestige. However, off late, accuracy and reliability of JIF for evaluation of scientific journals has been increasingly questioned by numerous stakeholders in the field of scholarly publications. Having realized the perils and pitfalls of JIF, there is an increasing understanding among academia to develop and consider alternatives to the traditional JIF. It is possibly time for all concerned to understand the pros and cons of JIF to overcome this obsession. Limitations of JIF and possible alternative and emerging bibliometric indicators are being discussed in this article for the benefit of the readers of MJAFI.
http://ift.tt/2nV24uM
Physical examination: The dying art
Publication date: Available online 3 April 2017
Source:Medical Journal Armed Forces India
Author(s): Bipin Puri, V. Shankar Raman
http://ift.tt/2n8VxPU
Simplified edentulous treatment: A multicenter randomized controlled trial to evaluate the timing and clinical outcomes of the technique
Source:The Journal of Prosthetic Dentistry
Author(s): Paola Ceruti, Nicola Mobilio, Elisabetta Bellia, Andrea Borracchini, Santo Catapano, Gianfranco Gassino
Statement of problemThe time and cost of conventional complete denture procedures have been questioned in favor of simplified and faster methods. Whether the simplified edentulous treatment (SET) method yields complete dentures with acceptable outcomes is unclear.PurposeThe purpose of this randomized clinical trial (RCT) was to evaluate the outcomes of 2 techniques in providing complete dentures: the conventional and the SET methods.Material and methodsThree Italian academic institutions participated in this single-blind parallel RCT. In total, 64 participants were selected and agreed to join the study. They were allocated randomly to 1 of 2 treatment groups, the conventional and SET group: 32 participants per group, 50% women in each group. Treatment was provided by final year predoctoral dental students. The time required for the clinical and laboratory procedures, the number of clinical sessions, and the laboratory returns were recorded. The clinical quality of the dentures and participant satisfaction were evaluated using questionnaires. Differences between treatment group outcomes were analyzed with 2-tailed independent sample Student t tests for clinical and technical timing and clinical and technical steps and Mann-Whitney U tests for denture quality and participant satisfaction (α=.05).ResultsThe clinical time required (−34%, P<.001), number of clinical sessions (−34%, P<.001), and laboratory returns (−46.5%, P<.001) were significantly lower for the SET than for the conventional method. The laboratory time required (−10.6%) was not significantly less with the SET method (P=.06). Participant satisfaction (P=.816) and prosthodontist ratings of denture quality (P=.539) were comparable between the groups. The participants appreciated the reduced number of clinical sessions with SET (P=.003).ConclusionsSimplified edentulous treatment may be considered a reliable method for providing complete dentures in a shorter timeframe while maintaining denture quality and patient satisfaction.
http://ift.tt/2ozVEnz
Restoration of a large class IV fracture using direct composite resin: A clinical report
Source:The Journal of Prosthetic Dentistry
Author(s): Mario F. Romero, Jamie Austin Grant, Megan Todd
Restoration of anterior tooth fractures is a common dental procedure. Both direct and indirect options are clinically acceptable to repair fractured teeth. For a large class IV fracture, treatment planning is time consuming, and the artistic skills necessary to achieve optimal results can be daunting. This clinical report describes a step-by-step protocol for achieving highly esthetic direct anterior restorations.
http://ift.tt/2nGV0RK
A combined digital and stereophotogrammetric technique for rehabilitation with immediate loading of complete-arch, implant-supported prostheses: A randomized controlled pilot clinical trial
Source:The Journal of Prosthetic Dentistry
Author(s): María Peñarrocha-Diago, José Carlos Balaguer-Martí, David Peñarrocha-Oltra, José Francisco Balaguer-Martínez, Miguel Peñarrocha-Diago, Rubén Agustín-Panadero
Statement of problemTraditional impressions for complete-arch restorations are complex and time-consuming, and they can be uncomfortable for the patient. New digital techniques such as stereophotogrammetry may mitigate this.PurposeThe purpose of this randomized controlled pilot clinical trial was to compare the patient and dentist satisfaction and work times of traditional impressions (control group) and digital impressions with stereophotogrammetry in complete-arch, implant-supported prostheses. Success rates, implant survival, marginal bone loss around the dental implants, and prosthesis survival were also analyzed.Material and methodsThis randomized controlled pilot clinical trial included 18 participants who received 131 dental implants. Implant impressions in the experimental group were made with stereophotogrammetry (8 participants with 66 implants), while traditional impressions were made in the control group (10 participants with 65 implants). Working times were measured in minutes starting from removal of the healing abutments to their replacement after the impression. Patient and dentist satisfaction was analyzed using a questionnaire with a visual analog scale, and implant success was assessed using the Buser success criteria. Prosthesis survival was defined as the presence of the prosthesis in the mouth, without screw loosening or fracture.ResultsThe work times were 15.6 (experimental group) and 20.5 minutes (control group) (P<.001). The patient satisfaction scores were 8.8 in the experimental and 7.9 in the control group (P=.02). The dentist satisfaction scores were 9.1 in the experimental group and 8.5 in the control group (P=.03). The implant success rate was 100% in both groups. Marginal bone loss was 0.6 ±0.5 mm (experimental group) and 0.6 ±0.2 mm (control group) (P=.72).ConclusionsDigital impressions using stereophotogrammetry may be an alternative to traditional impressions. Patient and dentist satisfaction improved, and the work time was reduced in the experimental group. No statistically significant differences were found in terms of the implant success rate, implant survival, marginal bone loss, or prosthesis survival between the 2 groups.
http://ift.tt/2oA7nCI
Computer-aided analysis of digital dental impressions obtained from intraoral and extraoral scanners
Source:The Journal of Prosthetic Dentistry
Author(s): Lauren Oliveira Lima Bohner, Graziela De Luca Canto, Bruno Silva Marció, Dalva Cruz Laganá, Newton Sesma, Pedro Tortamano Neto
Statement of problemThe internal and marginal adaptation of a computer-aided design and computer-aided manufacturing (CAD-CAM) prosthesis relies on the quality of the 3-dimensional image. The quality of imaging systems requires evaluation.PurposeThe purpose of this in vitro study was to evaluate and compare the trueness of intraoral and extraoral scanners in scanning-prepared teeth.Material and methodsTen acrylic resin teeth to be used as a reference dataset were prepared according to standard guidelines and scanned with an industrial computed tomography system. Data were acquired with 4 scanner devices (n=10): the Trios intraoral scanner (TIS), the D250 extraoral scanner (DES), the Cerec Bluecam intraoral scanner (CBIS), and the Cerec InEosX5 extraoral scanner (CIES). For intraoral scanners, each tooth was digitized individually. Extraoral scanning was obtained from dental casts of each prepared tooth. The discrepancy between each scan and its respective reference model was obtained by deviation analysis (μm) and volume/area difference (μm). Statistical analysis was performed using linear models for repeated measurement factors test and 1-way ANOVA (α=.05).ResultsNo significant differences in deviation values were found among scanners. For CBIS and CIES, the deviation was significantly higher (P<.05) for occlusal and cervical surfaces. With regard to volume differences, no statistically significant differences were found (TIS=340 ±230 μm; DES=380 ±360 μm; CBIS=780 ±770 μm; CIES=340 ±300 μm).ConclusionsIntraoral and extraoral scanners showed similar trueness in scanning-prepared teeth. Higher discrepancies are expected to occur in the cervical region and on the occlusal surface.
http://ift.tt/2nHeUMf
Assessment of in vitro dopamine-neuroblastoma cell interactions with a bioelectric biosensor: perspective for a novel in vitro functional assay for dopamine agonist/antagonist activity
Publication date: 1 August 2017
Source:Talanta, Volume 170
Author(s): Theofylaktos Apostolou, Georgia Moschopoulou, Evdokia Kolotourou, Spyridon Kintzios
Current receptor-binding assays for dopamine do not measure the in vitro whole cellular response against dopamine or potential agonist/antagonist molecules. We herewith report the development of a novel functional assay concept for studying the in vitro interaction of the neurotransmitter dopamine with neural cells bearing dopamine receptors. The concept is based on the ultra-rapid measurement of changes in the electric properties of cultured N2a mouse neuroblastoma cells (corresponding to cumulative changes of the cell membrane potential). A close relationship between cumulative cell membrane potential and dopamine concentration was observed. Membrane depolarization was observed at nanomolar dopamine concentrations, while hyperpolarization was associated with micromolar ones. Treatment with the dopamine D2-receptor antagonist eticlopride resulted to a concentration-dependent membrane depolarization. Treatment with sodium chloride caused considerable weakening of the dopamine-associated hyperpolarization effect. The observed bioelectric response to dopamine was highly inversely correlated with the pattern of dopamine release-uptake balance by N2a cells, as determined with cyclic voltammetry. The bioelectric approach was also used to evaluate the dopaminergic activity of chaste tree (Vitex agnus-castus) extracts. The novel assay concept offers promising perspectives for the development of advanced companion diagnostics system for the high throughput, fast functional characterization of neurotransmitter agonists and antagonists.
Graphical abstract
http://ift.tt/2nBmbMY
Intracellular DNA and microRNA sensing based on metal-organic framework nanosheets with enzyme-free signal amplification
Publication date: 1 August 2017
Source:Talanta, Volume 170
Author(s): Wen-Jun Song
A new fluorescent sensing platform based on ultrathin metal-organic framework (MOF) nanosheets (MnDMS) was prepared from the flexible ligand 2,2-dimethylsuccinate and Mn ions. The MnDMS nanoparticles can be obtained by simply ultrasonication of the MnDMS crystal, and then can be exfoliated into nanosheets by Li-intercalation method. The MnDMS nanosheets can be easily assembled with biological probes, leading to efficient fluorescence quenching of the fluorophore tagged ssDNA and microRNA (miRNA). By using a hybridization chain reaction (HCR) strategy, the fluorescence signal can be obviously amplified. A good linearity was obtained from 1 pM to 200 pM of target ssDNA, with a detection limit of 0.2 pM. The HCR/MnDMS system provides an effective way to monitor miRNA in living cells. Therefore, the MnDMS nanosheets can be used as a new kind of platform in biomedical sensing applications.
Graphical abstract
http://ift.tt/2nBwOPD
-
Summary Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an un...
-
The online platform for Taylor & Francis Online content New for Canadian Journal of Remote Sen...
