Non-cell Autonomous OTX2 Homeoprotein Regulates Visual Cortex Plasticity Through Gadd45b/g

Abstract

The non-cell autonomous transfer of OTX2 homeoprotein transcription factor into juvenile mouse cerebral cortex regulates parvalbumin interneuron maturation and critical period timing. By analyzing gene expression in primary visual cortex of wild-type and Otx2^+/GFP mice at plastic and nonplastic ages, we identified several putative genes implicated in Otx2-dependent visual cortex plasticity for ocular dominance. Cortical OTX2 infusion in juvenile mice induced Gadd45b/g expression through direct regulation of transcription. Intriguingly, a reverse effect was found in the adult, where reducing cortical OTX2 resulted in Gadd45b/g upregulation. Viral expression of Gadd45b in adult visual cortex directly induced ocular dominance plasticity with concomitant changes in MeCP2 foci within parvalbumin interneurons and in methylation states of several plasticity gene promoters, suggesting epigenetic regulation. This interaction provides a molecular mechanism for OTX2 to trigger critical period plasticity yet suppress adult plasticity.

https://ift.tt/2jZ0WoL

Term or Preterm Cesarean Section Delivery Does Not Lead to Long-term Detrimental Consequences in Mice

Abstract

Epidemiological studies have provided contradictory data on the deleterious sequels of cesarean section (C-section) delivery and their links with developmental brain disorders such as Autism Spectrum Disorders. To gain better insight on these issues, we have now compared physiological, morphological, and behavioral parameters in vaginal, term, and preterm C-section delivered mice. We report that C-section delivery does not lead to long-term behavioral alterations though preterm C-section delivery modifies communicative behaviors in pups. Moreover, C-section delivery neither alters the gamma-aminobutyric acid (GABA) developmental excitatory to inhibitory shift nor the frequency or amplitude of glutamatergic and GABAergic postsynaptic currents in hippocampal pyramidal neurons. However, these neurons present an underdeveloped dendritic arbor at birth in pups born by C-section delivery, but this difference disappears 1 day later suggesting an accelerated growth after birth. Therefore, C-section delivery, with prematurity as an aggravating factor, induces transient developmental delays but neither impacts the GABA developmental sequence nor leads to long-term consequences in mice. The deleterious sequels of C-section delivery described in epidemiological studies might be due to a perinatal insult that could be aggravated by C-section delivery.

https://ift.tt/2wIxD2Z

Sex Differences in the Adult Human Brain: Evidence from 5216 UK Biobank Participants

Abstract

Sex differences in the human brain are of interest for many reasons: for example, there are sex differences in the observed prevalence of psychiatric disorders and in some psychological traits that brain differences might help to explain. We report the largest single-sample study of structural and functional sex differences in the human brain (2750 female, 2466 male participants; mean age 61.7 years, range 44–77 years). Males had higher raw volumes, raw surface areas, and white matter fractional anisotropy; females had higher raw cortical thickness and higher white matter tract complexity. There was considerable distributional overlap between the sexes. Subregional differences were not fully attributable to differences in total volume, total surface area, mean cortical thickness, or height. There was generally greater male variance across the raw structural measures. Functional connectome organization showed stronger connectivity for males in unimodal sensorimotor cortices, and stronger connectivity for females in the default mode network. This large-scale study provides a foundation for attempts to understand the causes and consequences of sex differences in adult brain structure and function.

https://ift.tt/2IKNnHv

Local Cortical Gyrification is Increased in Children With Autism Spectrum Disorders, but Decreases Rapidly in Adolescents

Abstract

Extensive MRI evidence indicates early brain overgrowth in autism spectrum disorders (ASDs). Local gyrification may reflect the distribution and timing of aberrant cortical expansion in ASDs. We examined MRI data from (Study 1) 64 individuals with ASD and 64 typically developing (TD) controls (7–19 years), and from (Study 2) an independent sample from the Autism Brain Imaging Data Exchange (n = 31/group). Local Gyrification Index (lGI), cortical thickness (CT), and surface area (SA) were measured. In Study 1, differences in lGI (ASD > TD) were found in left parietal and temporal and right frontal and temporal regions. lGI decreased bilaterally with age, but more steeply in ASD in left precentral, right lateral occipital, and middle frontal clusters. CT differed between groups in right perisylvian cortex (TD > ASD), but no differences were found for SA. Partial correlations between lGI and CT were generally negative, but associations were weaker in ASD in several clusters. Study 2 results were consistent, though less extensive. Altered gyrification may reflect unique information about the trajectory of cortical development in ASDs. While early overgrowth tends to be undetectable in later childhood in ASDs, findings may indicate that a trace of this developmental abnormality could remain in a disorder-specific pattern of gyrification.

https://ift.tt/2wHp4W0

Multiple Regions of a Cortical Network Commonly Encode the Meaning of Words in Multiple Grammatical Positions of Read Sentences

Abstract

Deciphering how sentence meaning is represented in the brain remains a major challenge to science. Semantically related neural activity has recently been shown to arise concurrently in distributed brain regions as successive words in a sentence are read. However, what semantic content is represented by different regions, what is common across them, and how this relates to words in different grammatical positions of sentences is weakly understood. To address these questions, we apply a semantic model of word meaning to interpret brain activation patterns elicited in sentence reading. The model is based on human ratings of 65 sensory/motor/emotional and cognitive features of experience with words (and their referents). Through a process of mapping functional Magnetic Resonance Imaging activation back into model space we test: which brain regions semantically encode content words in different grammatical positions (e.g., subject/verb/object); and what semantic features are encoded by different regions. In left temporal, inferior parietal, and inferior/superior frontal regions we detect the semantic encoding of words in all grammatical positions tested and reveal multiple common components of semantic representation. This suggests that sentence comprehension involves a common core representation of multiple words' meaning being encoded in a network of regions distributed across the brain.

https://ift.tt/2L6naS3

Impact of steroid hormones E2 and P on the NLRP3/ASC/Casp1 axis in primary mouse astroglia and BV-2 cells after in vitro hypoxia

Publication date: Available online 15 May 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Alexander Slowik, Leoni Lammerding, Adib Zendedel, Pardes Habib, Cordian Beyer
Clinical and animal model studies have demonstrated the neuroprotective and anti-inflammatory effects of 17beta-estradiol (E2) and progesterone (P) in different disease models of the central nervous system (CNS) including ischemic stroke. Inflammasomes are involved in the interleukin-1 beta (IL1beta) maturation, in particular, NLRP3, the adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) and the active caspase-1 (Casp1) form. Recently, we showed that administration of E2 or P selectively regulated these components after experimental ischemic stroke in rats. Therefore, we investigated the impact of E2 and P on the NLRP3/ASC/Casp1 axis in the murine microglia-like cell line BV-2 cells and primary astrocytes after short-term in vitro hypoxia.The inflammatory cytokine IL1beta but not IL18 was increased after short-term hypoxia in astroglia and BV-2 cells. The same applied to NLPR3 and ASC. Casp1 activity was also elevated in astroglia and BV-2 cells after hypoxia. The administration of E2 or P selectively dampened IL1beta, ASC and NLRP3 expression mainly in BV-2 cells. Both steroid hormones failed to reduce Casp1 activity after hypoxia.We conclude that E2- and P-mediated anti-inflammatory mechanisms occur upstream of Casp1 through the regulation of NLRP3 and its adaptor ASC.



https://ift.tt/2rKOhcx

EURAPS Editorial: BIA-ALCL, a brief overview

The history of breast implants includes important technological breakthroughs, but also safety controversies such as the 1992 FDA moratorium against silicone, the 2010 PIP implant scandal, and the 2015 Silimed ban.1–3 Nevertheless, the popularity of breast augmentation continues to grow, and millions of patients receive breast implants each year.4

https://ift.tt/2KsKCro

Multidisciplinary management of periocular tumour excision repair

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2IGmZOX

Prominent nose, its modalities and their treatment

Abstract

Background

Size of the nose varies in the different parts of the world, and perception of what is the aesthetically acceptable nose shows large differences depending on the ethnic background, type of the society, gender and age. Nose which is generally larger than the average nose in a given society, particularly regarding the height of its nasal bridge, could be defined as a prominent nose.

Methods

Photographs of the 414 consecutive patients who underwent rhinoplasty by the author during the years 2014 and 2015 were reviewed. Attention was directed to the following outer features: overall length, height and width of the nose, nasofrontal angle, nasolabial angle, nose-lip and nose-chin relations, shape and position of the chin and the evaluation of the respiratory function. Among determinants was formula of Goode, which delineates the approximate relationship between tip projection and nasal length.

Results

A total of 144 patients, 112 females and 31 males, who fulfilled criteria of prominent nose were selected for the further analysis. A total of 70% of the patients were of Middle-Eastern origin. The following four types of prominent nose were recognised: (1) short prominent nose, or tension nose was present in 38 patients. It has overprojecting dorsum, which usually forms a hump. Nasolabial angle is obtuse, and nasal spina is frequently overgrown. The rate of functional problems is quite high due to the overdevelopment and subsequent deviation of the septal cartilage. (2) Long prominent nose, present in 96 patients, usually has an arched dorsum, sharp NL angle and drooping tip. (3) Long nose depending on the height of the dorsum in the lateral projection can be the low long nose and it was seen in four patients, or when the nose is both long and the tip is overprojecting, it is called Pinocchio nose and it was present in eight patients. (4) Rhinomegaly is the term describing nose which is very large in all dimensions, the height, length and width and was also seen in eight patients.

Conclusions

Prominent nose has several modalities and each of them requires different techniques applied during the surgical intervention. Both aesthetic and functional topics are frequently present, and multiple nasal structures, both external and internal, are commonly involved. In the aesthetically pleasing Caucasian nose, Goode's ratio should equal 0.55 to 0.60. If there is before operation unrecognised deviation from this norm, which is also persistent after the rhinoplasty, the final result will be substandard.

Level of Evidence IV, risk / prognostic study.

https://ift.tt/2Kqj5XF

When the Gut Gets Tough, the Enterocytes Get Going

Publication date: 15 May 2018
Source:Immunity, Volume 48, Issue 5
Author(s): Grischa Y. Chen, Janelle S. Ayres
It is assumed that collateral damage from the immune system drives intestinal epithelial cell (IEC) expulsion during enteric infections. In this issue of Immunity, Zhai et al. (2018) describe how Drosophila's canonical immune deficiency (Imd) pathway programs IEC delamination in the gut.

Teaser

It is assumed that collateral damage from the immune system drives intestinal epithelial cell (IEC) expulsion during enteric infections. In this issue of Immunity, Zhai et al. (2018) describe how Drosophila's canonical immune deficiency (Imd) pathway programs IEC delamination in the gut.


https://ift.tt/2jXBujA

A Worm’s Gut Feelings: Neuronal Muscarinic and Epithelial Canonical Wnt Pathways Promote Antimicrobial Defense

Publication date: 15 May 2018
Source:Immunity, Volume 48, Issue 5
Author(s): Romana R. Gerner, Manuela Raffatellu
Molecular mechanisms connecting the gut-brain axis to immunity remain elusive. In this issue of Immunity, Labed et al. (2018) demonstrate that two evolutionarily conserved signaling mechanisms, the neuronal muscarinic and the epithelial Wnt pathways, together induce antimicrobial peptide expression that protects Caenorhabditis elegans against intestinal infection.

Teaser

Molecular mechanisms connecting the gut-brain axis to immunity remain elusive. In this issue of Immunity, Labed et al. (2018) demonstrate that two evolutionarily conserved signaling mechanisms, the neuronal muscarinic and the epithelial Wnt pathways, together induce antimicrobial peptide expression that protects Caenorhabditis elegans against intestinal infection.


https://ift.tt/2Io9JLH

TREMendous 2 Be Social

Publication date: 15 May 2018
Source:Immunity, Volume 48, Issue 5
Author(s): Narghes Calcagno, Caroline Baufeld, Charlotte Madore, Oleg Butovsky
TREM2 is known for its role in microglial phagocytosis and in neurodegenerative diseases. In this issue of Immunity, Filipello et al. (2018) show that microglial TREM2 is required for synaptic pruning in early development. TREM2-deficient mice show altered social behavior in adulthood, linking TREM2 to neurodevelopmental disease.

Teaser

TREM2 is known for its role in microglial phagocytosis and in neurodegenerative diseases. In this issue of Immunity, Filipello et al. (2018) show that microglial TREM2 is required for synaptic pruning in early development. TREM2-deficient mice show altered social behavior in adulthood, linking TREM2 to neurodevelopmental disease.


https://ift.tt/2IGkNab

Getting DAMP(s) Wets the Whistle for Neutrophil Recruitment

Publication date: 15 May 2018
Source:Immunity, Volume 48, Issue 5
Author(s): Emily R. Watts, Sarah R. Walmsley
Neutrophil recruitment in response to pathogen invasion is mediated through "self" tissue damage signals (DAMPs) and pathogen associated signals (PAMPs). In this issue of Immunity, Huang and Niethammer, (2018) demonstrate that DAMP signaling is a prerequisite for neutrophil recruitment.

Teaser

Neutrophil recruitment in response to pathogen invasion is mediated through "self" tissue damage signals (DAMPs) and pathogen associated signals (PAMPs). In this issue of Immunity, Huang and Niethammer, (2018) demonstrate that DAMP signaling is a prerequisite for neutrophil recruitment.


https://ift.tt/2jY2ZJL

Conditional Gene-Targeting in Mice: Problems and Solutions

Publication date: 15 May 2018
Source:Immunity, Volume 48, Issue 5
Author(s): Burkhard Becher, Ari Waisman, Li-Fan Lu




https://ift.tt/2IpljGi

Trained Microglia Trigger Memory Loss

Publication date: 15 May 2018
Source:Immunity, Volume 48, Issue 5
Author(s): Iva Lelios, Melanie Greter
Innate immune training is a recently described mechanism that allows innate cells to recollect a previous inflammatory episode. In a recent issue of Nature, Wendeln et al. (2018) show that peripheral inflammation can alter long-term microglia function, influencing neuropathology later in life.

Teaser

Innate immune training is a recently described mechanism that allows innate cells to recollect a previous inflammatory episode. In a recent issue of Nature, Wendeln et al. (2018) show that peripheral inflammation can alter long-term microglia function, influencing neuropathology later in life.


https://ift.tt/2jXB4tw

Peek-Peak-Pique: Repeating Motifs of Subtle Variance Are Targets for Potent Malaria Antibodies

Publication date: 15 May 2018
Source:Immunity, Volume 48, Issue 5
Author(s): Stephen W. Scally, Jean-Philippe Julien
Biomedical interventions to curb malaria-causing Plasmodium falciparum (Pf) infections are critically needed. Two studies in Nature Medicine,Kisalu et al. (2018) and Tan et al. (2018), report the isolation of potent human antibodies that target a new epitope on Pf sporozoites and mediate effective parasite inhibition in pre-clinical models.

Teaser

Biomedical interventions to curb malaria-causing Plasmodium falciparum (Pf) infections are critically needed. Two studies in Nature Medicine,Kisalu et al. (2018) and Tan et al. (2018), report the isolation of potent human antibodies that target a new epitope on Pf sporozoites and mediate effective parasite inhibition in pre-clinical models.


https://ift.tt/2Im67cZ

HIV-1 Vaccines Based on Antibody Identification, B Cell Ontogeny, and Epitope Structure

Publication date: 15 May 2018
Source:Immunity, Volume 48, Issue 5
Author(s): Peter D. Kwong, John R. Mascola
HIV-1 vaccine development has been stymied by an inability to induce broadly reactive neutralizing antibodies to the envelope (Env) trimer, the sole viral antigen on the virion surface. Antibodies isolated from HIV-1-infected donors, however, have been shown to recognize all major exposed regions of the prefusion-closed Env trimer, and an emerging understanding of the immunological and structural characteristics of these antibodies and the epitopes they recognize is enabling new approaches to vaccine design. Antibody lineage-based design creates immunogens that activate the naive ancestor-B cell of a target antibody lineage and that mature intermediate-B cells toward effective neutralization, with proof of principle achieved with select HIV-1-neutralizing antibody lineages in human-gene knock-in mouse models. Epitope-based vaccine design involves the engineering of sites of Env vulnerability as defined by the recognition of broadly neutralizing antibodies, with cross-reactive neutralizing antibodies elicited in animal models. Both epitope-based and antibody lineage-based HIV-1 vaccine approaches are being readied for human clinical trials.

Teaser

Kwong and Mascola review vaccine approaches to overcome the formidable challenge of eliciting effective antibodies against HIV-1. The structural and immunological information provided by analysis of infection-elicited broadly neutralizing antibodies provides a framework for antibody-to-vaccine approaches of vaccine design.


https://ift.tt/2IFgEmW

Targeting the Latent Reservoir for HIV-1

Publication date: 15 May 2018
Source:Immunity, Volume 48, Issue 5
Author(s): Srona Sengupta, Robert F. Siliciano
Antiretroviral therapy can effectively block HIV-1 replication and prevent or reverse immunodeficiency in HIV-1-infected individuals. However, viral replication resumes within weeks of treatment interruption. The major barrier to a cure is a small pool of resting memory CD4⁺ T cells that harbor latent HIV-1 proviruses. This latent reservoir is now the focus of an intense international research effort. We describe how the reservoir is established, challenges involved in eliminating it, and pharmacologic and immunologic strategies for targeting this reservoir. The development of a successful cure strategy will most likely require understanding the mechanisms that maintain HIV-1 proviruses in a latent state and pathways that drive the proliferation of infected cells, which slows reservoir decay. In addition, a cure will require the development of effective immunologic approaches to eliminating infected cells. There is renewed optimism about the prospect of a cure, and the interventions discussed here could pave the way.

Teaser

Developing a cure for HIV-1 requires understanding the mechanisms of HIV-1 persistence in the latent reservoir. In this review, we discuss historical and recent paradigms in the HIV-1 persistence field as well as novel immunologic and pharmacologic strategies for eliminating this reservoir.


https://ift.tt/2Is7eIl

The Chaperone UNC93B1 Regulates Toll-like Receptor Stability Independently of Endosomal TLR Transport

Publication date: 15 May 2018
Source:Immunity, Volume 48, Issue 5
Author(s): Karin Pelka, Damien Bertheloot, Elisa Reimer, Kshiti Phulphagar, Susanne V. Schmidt, Anette Christ, Rainer Stahl, Nicki Watson, Kensuke Miyake, Nir Hacohen, Albert Haas, Melanie M. Brinkmann, Ann Marshak-Rothstein, Felix Meissner, Eicke Latz
Unc-93 homolog B1 (UNC93B1) is a key regulator of nucleic acid (NA)-sensing Toll-like receptors (TLRs). Loss of NA-sensing TLR responses in UNC93B1-deficient patients facilitates Herpes simplex virus type 1 (HSV-1) encephalitis. UNC93B1 is thought to guide NA-sensing TLRs from the endoplasmic reticulum (ER) to their respective endosomal signaling compartments and to guide the flagellin receptor TLR5 to the cell surface, raising the question of how UNC93B1 mediates differential TLR trafficking. Here, we report that UNC93B1 regulates a step upstream of the differential TLR trafficking process. We discovered that UNC93B1 deficiency resulted in near-complete loss of TLR3 and TLR7 proteins in primary splenic mouse dendritic cells and macrophages, showing that UNC93B1 is critical for maintaining TLR expression. Notably, expression of an ER-retained UNC93B1 version was sufficient to stabilize TLRs and largely restore endosomal TLR trafficking and activity. These data are critical for an understanding of how UNC93B1 can regulate the function of a broad subset of TLRs.

Graphical abstract

Teaser

UNC93B1 is known as a trafficking chaperone for both endosomal TLRs and cell-surface TLR5, but how UNC93B1 transports its client TLRs to different compartments remains to be determined. Pelka and colleagues show that, in fact, UNC93B1 functions upstream of differential trafficking pathways and is crucial for stabilizing UNC93B1-dependent TLRs.


https://ift.tt/2k0ZulS

Expression of the DNA-Binding Factor TOX Promotes the Encephalitogenic Potential of Microbe-Induced Autoreactive CD8+ T Cells

Publication date: 15 May 2018
Source:Immunity, Volume 48, Issue 5
Author(s): Nicolas Page, Bogna Klimek, Mathias De Roo, Karin Steinbach, Hadrien Soldati, Sylvain Lemeille, Ingrid Wagner, Mario Kreutzfeldt, Giovanni Di Liberto, Ilena Vincenti, Thomas Lingner, Gabriela Salinas, Wolfgang Brück, Mikael Simons, Rabih Murr, Jonathan Kaye, Dietmar Zehn, Daniel D. Pinschewer, Doron Merkler
Infections are thought to trigger CD8⁺ cytotoxic T lymphocyte (CTL) responses during autoimmunity. However, the transcriptional programs governing the tissue-destructive potential of CTLs remain poorly defined. In a model of central nervous system (CNS) inflammation, we found that infection with lymphocytic choriomeningitis virus (LCMV), but not Listeria monocytogenes (Lm), drove autoimmunity. The DNA-binding factor TOX was induced in CTLs during LCMV infection and was essential for their encephalitogenic properties, and its expression was inhibited by interleukin-12 during Lm infection. TOX repressed the activity of several transcription factors (including Id2, TCF-1, and Notch) that are known to drive CTL differentiation. TOX also reduced immune checkpoint sensitivity by restraining the expression of the inhibitory checkpoint receptor CD244 on the surface of CTLs, leading to increased CTL-mediated damage in the CNS. Our results identify TOX as a transcriptional regulator of tissue-destructive CTLs in autoimmunity, offering a potential mechanistic link to microbial triggers.

Graphical abstract

Teaser

Little is known about the transcriptional programs that drive the tissue destructive capacity of effector CD8⁺ T cells during autoimmunity. In an animal model of CNS inflammation, Page et al. demonstrate that expression of the DNA-binding factor TOX promotes the encephalitogenic potential of pathogen-primed CD8⁺ T cells and that TOX expression is determined by the microbial context of CTL priming.


https://ift.tt/2Ip9ZtV

Trained Memory of Human Uterine NK Cells Enhances Their Function in Subsequent Pregnancies

Publication date: 15 May 2018
Source:Immunity, Volume 48, Issue 5
Author(s): Moriya Gamliel, Debra Goldman-Wohl, Batya Isaacson, Chamutal Gur, Natan Stein, Rachel Yamin, Michael Berger, Myriam Grunewald, Eli Keshet, Yoach Rais, Chamutal Bornstein, Eyal David, Adam Jelinski, Iris Eisenberg, Caryn Greenfield, Arbel Ben-David, Tal Imbar, Ronit Gilad, Ronit Haimov-Kochman, David Mankuta, Matan Elami-Suzin, Ido Amit, Jacob H. Hanna, Simcha Yagel, Ofer Mandelboim
Natural killer cells (NKs) are abundant in the human decidua, regulating trophoblast invasion and angiogenesis. Several diseases of poor placental development are associated with first pregnancies, so we thus looked to characterize differences in decidual NKs (dNKs) in first versus repeated pregnancies. We discovered a population found in repeated pregnancies, which has a unique transcriptome and epigenetic signature, and is characterized by high expression of the receptors NKG2C and LILRB1. We named these cells Pregnancy Trained decidual NK cells (PTdNKs). PTdNKs have open chromatin around the enhancers of IFNG and VEGFA. Activation of PTdNKs led to increased production and secretion of IFN-γ and VEGFα, with the latter supporting vascular sprouting and tumor growth. The precursors of PTdNKs seem to be found in the endometrium. Because repeated pregnancies are associated with improved placentation, we propose that PTdNKs, which are present primarily in repeated pregnancies, might be involved in proper placentation.

Graphical abstract

Teaser

Natural killer cells are present in the human decidua, regulating trophoblast invasion and angiogenesis. Here, Gamliel et al. report on a special subset of human decidual natural killer cells, which "remember" pregnancy and better support subsequent pregnancies. This might explain why first pregnancies are at increased risk of developing diseases of poor placentation.


https://ift.tt/2IP740K

Intestinal Epithelial Wnt Signaling Mediates Acetylcholine-Triggered Host Defense against Infection

Publication date: 15 May 2018
Source:Immunity, Volume 48, Issue 5
Author(s): Sid Ahmed Labed, Khursheed A. Wani, Sakthimala Jagadeesan, Abdul Hakkim, Mehran Najibi, Javier Elbio Irazoqui
Regulated antimicrobial peptide expression in the intestinal epithelium is key to defense against infection and to microbiota homeostasis. Understanding the mechanisms that regulate such expression is necessary for understanding immune homeostasis and inflammatory disease and for developing safe and effective therapies. We used Caenorhabditis elegans in a preclinical approach to discover mechanisms of antimicrobial gene expression control in the intestinal epithelium. We found an unexpected role for the cholinergic nervous system. Infection-induced acetylcholine release from neurons stimulated muscarinic signaling in the epithelium, driving downstream induction of Wnt expression in the same tissue. Wnt induction activated the epithelial canonical Wnt pathway, resulting in the expression of C-type lectin and lysozyme genes that enhanced host defense. Furthermore, the muscarinic and Wnt pathways are linked by conserved transcription factors. These results reveal a tight connection between the nervous system and the intestinal epithelium, with important implications for host defense, immune homeostasis, and cancer.

Graphical abstract

Teaser

How intestinal epithelial antimicrobial defense functions are regulated is poorly understood. Using Caenorhabditis elegans, Labed et al. found infection-triggered neuronal acetylcholine release, driving intestinal defense gene expression via conserved muscarinic and Wnt pathways. This newly identified pathway may be relevant to the microbiota-gut-brain axis and immune homeostasis in humans.


https://ift.tt/2Im65ln

Dietary Fiber Confers Protection against Flu by Shaping Ly6c− Patrolling Monocyte Hematopoiesis and CD8+ T Cell Metabolism

Publication date: 15 May 2018
Source:Immunity, Volume 48, Issue 5
Author(s): Aurélien Trompette, Eva S. Gollwitzer, Céline Pattaroni, Isabel C. Lopez-Mejia, Erika Riva, Julie Pernot, Niki Ubags, Lluis Fajas, Laurent P. Nicod, Benjamin J. Marsland
Dietary fiber protects against chronic inflammatory diseases by dampening immune responses through short-chain fatty acids (SCFAs). Here we examined the effect of dietary fiber in viral infection, where the anti-inflammatory properties of SCFAs in principle could prevent protective immunity. Instead, we found that fermentable dietary fiber increased survival of influenza-infected mice through two complementary mechanisms. High-fiber diet (HFD)-fed mice exhibited altered bone marrow hematopoiesis, characterized by enhanced generation of Ly6c⁻ patrolling monocytes, which led to increased numbers of alternatively activated macrophages with a limited capacity to produce the chemokine CXCL1 in the airways. Blunted CXCL1 production reduced neutrophil recruitment to the airways, thus limiting tissue immunopathology during infection. In parallel, diet-derived SCFAs boosted CD8⁺ T cell effector function by enhancing cellular metabolism. Hence, dietary fermentable fiber and SCFAs set an immune equilibrium, balancing innate and adaptive immunity so as to promote the resolution of influenza infection while preventing immune-associated pathology.

Graphical abstract

Teaser

Trompette et al. report that a diet rich in the fermentable fiber inulin and the associated metabolites—short-chain fatty acids—improve the response of mice to influenza infection by dampening deleterious immunopathology caused by neutrophils while enhancing anti-viral CD8⁺ T cell responses through a boost in T cell metabolism.


https://ift.tt/2IP6P5Q

Tissue Damage Signaling Is a Prerequisite for Protective Neutrophil Recruitment to Microbial Infection in Zebrafish

Publication date: 15 May 2018
Source:Immunity, Volume 48, Issue 5
Author(s): Cong Huang, Philipp Niethammer
Tissue damage and infection are deemed likewise triggers of innate immune responses. But whereas neutrophil responses to microbes are generally protective, neutrophil recruitment into damaged tissues without infection is deleterious. Why neutrophils respond to tissue damage and not just to microbes is unknown. Is it a flaw of the innate immune system that persists because evolution did not select against it, or does it provide a selective advantage? Here we dissect the contribution of tissue damage signaling to antimicrobial immune responses in a live vertebrate. By intravital imaging of zebrafish larvae, a powerful model for innate immunity, we show that prevention of tissue damage signaling upon microbial ear infection abrogates leukocyte chemotaxis and reduces animal survival, at least in part, through suppression of cytosolic phospholipase A2 (cPla2), which integrates tissue damage- and microbe-derived cues. Thus, microbial cues are insufficient, and damage signaling is essential for antimicrobial neutrophil responses in zebrafish.

Graphical abstract

Teaser

Tissue damage signaling in the absence of pathogens causes harmful neutrophil infiltration into damaged organs with no obvious benefit for the host. By intravital imaging of zebrafish larvae, Huang and Niethammer reveal a beneficial role for tissue damage signaling as prerequisite for rapid neutrophil recruitment to microbial infection sites.


https://ift.tt/2Im5hgf

Epigenomic-Guided Mass Cytometry Profiling Reveals Disease-Specific Features of Exhausted CD8 T Cells

Publication date: 15 May 2018
Source:Immunity, Volume 48, Issue 5
Author(s): Bertram Bengsch, Takuya Ohtani, Omar Khan, Manu Setty, Sasikanth Manne, Shaun O'Brien, Pier Federico Gherardini, Ramin Sedaghat Herati, Alexander C. Huang, Kyong-Mi Chang, Evan W. Newell, Niels Bovenschen, Dana Pe'er, Steven M. Albelda, E. John Wherry
Exhausted CD8 T (Tex) cells are immunotherapy targets in chronic infection and cancer, but a comprehensive assessment of Tex cell diversity in human disease is lacking. Here, we developed a transcriptomic- and epigenetic-guided mass cytometry approach to define core exhaustion-specific genes and disease-induced changes in Tex cells in HIV and human cancer. Single-cell proteomic profiling identified 9 distinct Tex cell clusters using phenotypic, functional, transcription factor, and inhibitory receptor co-expression patterns. An exhaustion severity metric was developed and integrated with high-dimensional phenotypes to define Tex cell clusters that were present in healthy subjects, common across chronic infection and cancer or enriched in either disease, linked to disease severity, and changed with HIV therapy. Combinatorial patterns of immunotherapy targets on different Tex cell clusters were also defined. This approach and associated datasets present a resource for investigating human Tex cell biology, with implications for immune monitoring and immunomodulation in chronic infections, autoimmunity, and cancer.

Graphical abstract

Teaser

Exhausted T (Tex) cells have poor function in chronic infections and cancer but can be therapeutically re-invigorated. Bengsch et al. use genes modified epigenetically during exhaustion and high-dimensional CyTOF profiling to define Tex cell heterogeneity in humans with HIV or lung cancer and link Tex cell features to disease progression and response to immunotherapy.


https://ift.tt/2IJrIzy

Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency

Publication date: 15 May 2018
Source:Immunity, Volume 48, Issue 5
Author(s): Yannick Simoni, Michael Fehlings, Henrik N. Kløverpris, Naomi McGovern, Si-Lin Koo, Chiew Yee Loh, Shawn Lim, Ayako Kurioka, Joannah R. Fergusson, Choong-Leong Tang, Ming Hian Kam, Koh Dennis, Tony Kiat Hon Lim, Alexander Chung Yaw Fui, Chan Weng Hoong, Jerry Kok Yen Chan, Maria Curotto de Lafaille, Sriram Narayanan, Sonia Baig, Muhammad Shabeer, Sue-Anne Ee Shiow Toh, Henry Kun Kiaang Tan, Rosslyn Anicete, Eng-Huat Tan, Angela Takano, Paul Klenerman, Alasdair Leslie, Daniel S.W. Tan, Iain Beehuat Tan, Florent Ginhoux, Evan W. Newell




https://ift.tt/2IplMrS

MicroRNA-21 up-regulates metalloprotease by down-regulating TIMP3 during cumulus cell-oocyte complex in vitro maturation

Publication date: Available online 15 May 2018
Source:Molecular and Cellular Endocrinology
Author(s): Bo PanJulang Li
Cumulus cells and the remodeling of their extracellular matrix around oocytes are essential for oocyte maturation and ovulation in the ovary. An important extracellular metalloprotease, ADAMTS1, and its partner VERSICAN, mediate essential cumulus-oocyte-complex (COC) structural remodeling. However, how the expression of these proteinases is regulated during oocyte maturation is unclear. Here we report that both ADAMTS1 and VERSICAN significantly increased in porcine cumulus cells during COC in vitro maturation (IVM). Interestingly, one of the tissue inhibitors of the metalloproteinase family member, TIMP3, was found to be significantly decreased in cumulus cells during this process. Down-regulation of TIMP3 using specific small interfering RNA decreased TIMP3 expression, while increased the levels of ADAMTS1 and VERSICAN, suggesting an inverse relationship between TIMP3, the metalloprotease, and the breakdown product of its substrate. MiR-21 significantly increased in cumulus cells during COC maturation. Knockdown of miR-21 in cumulus cells during COC maturation resulted in increased TIMP3 and decreased ADAMTS1 and VERSICAN expression, which is accompanied by a decrease in cumulus cell expansion and the ratio of oocytes that reached MII stage. In contrast, over-expression of miR-21 decreased TIMP3 and increased ADAMTS1, and enhanced cumulus cell expansion and oocyte maturation. Moreover, in silico prediction revealed that a miR-21 binding site is present at the 3-untranslated region (3-UTR) of the TIMP3 mRNA, which was further confirmed to be the target site of miR-21 by luciferase gene reporter assays. Our findings revealed that miR-21 promotes cumulus expansion and oocyte maturation via down-regulating TIMP3, and subsequent increase of ADAMTS1 and VERSICAN during in vitro COC maturation.



https://ift.tt/2wKbDET

Fetal meningocele manqué

MH Shabina Banu, Rajeswaran Rangasami, Indrani Suresh

Neurology India 2018 66(3):879-881



https://ift.tt/2IrWPvS

Necklace body myopathy: A rare entity

Aditya Choudhary, Saurabh Bansal, Louis Gaspar Balan, Manoj Goyal, Manish Modi

Neurology India 2018 66(3):841-842



https://ift.tt/2k0VUbu

Backward glance o'er travel'd roads

K Rajasekharan Nair

Neurology India 2018 66(3):604-609



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Department of Neurosurgery, Madurai Medical College and the development of neurosurgery in South Tamil Nadu

Subbiah Thiruppathy, Ramiah Manimaran, Gopalakrishnan M Niban, Natarajan Muthukumar

Neurology India 2018 66(3):807-814

The development of neurosurgery in South Tamil Nadu can be traced to the Department of Neurosurgery, Madurai Medical College and Government Rajaji Hospital, Madurai, Tamil Nadu, India. The hospital was established in the year 1940 and Madurai Medical College was started in 1954. Prof. M. Natarajan founded this department in September, 1963. This department has a Neurosurgery Residency Program that is 50 years old. The establishment of this department and its growth to its present stature is documented here.

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Founders of Indian Neurosciences: Professor Krishna Prasad Bhargava(5th October 1925- 16th August 1991)

Prakash N Tandon, Balram Bhargava

Neurology India 2018 66(3):610-612



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Giant cell tumor at the clivus: Not an area 51

Ayusman Satapathy, Manjul Tripathi, Ravi B Chauhan, Jenil Gurnaani, Sandeep Mohindra

Neurology India 2018 66(3):861-864



https://ift.tt/2IFhxfr

Evolution of concepts in the management of craniopharyngiomas: Lessons learnt from Prof. S.N. Bhagwati's article published in 1993

Harjinder S Bhatoe

Neurology India 2018 66(3):613-636



https://ift.tt/2Ind0dX

Wilder Penfield. The second career with other essays and addresses.

Sunil Pandya

Neurology India 2018 66(3):896-897



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False localizing oculomotor nerve palsy after endovascular coiling of a posterior communicating artery aneurysm

Boby V Maramattom, Vijay Jayakrishnan, Dilip Panikar, S Shyam Sundar

Neurology India 2018 66(3):830-832



https://ift.tt/2jYTTMT

Telemedicine and neurosciences

Krishnan Ganapathy

Neurology India 2018 66(3):642-651

It is well documented that there is an acute shortage of neurologists and neurosurgeons in India and globally. Despite all efforts, it will be impossible to make available neurospecialists in all suburban and rural areas. Simultaneously, there has been an exponential increase in the growth and development of Information and Communication Technology (ICT). Plummeting costs and unbelievable sophistication in the availability of user-friendly mobile video conferencing devices is making distance meaningless. Geography has become History! Worldwide, the ultraconservative health care industry, in particular, the medical community, has been uniformly slow to adopt and embrace the use of ICT to extend their clinical reach. In the last decade, however, specialists in all branches of neurosciences are slowly accepting the inevitable that telemedicine must and will have to be incorporated into the core of the healthcare delivery system. This literature review summarizes the current use of telemedicine in different subspecialties of neurosciences. The author defines the growth and development of clinical telemedicine in India with special reference to Neurosciences and attempts to show the stellar role telemedicine has to play in enhancing the services provided by doctors. As clinicians regularly using technology, it should not be difficult for us to convince our patients that today a virtual remote consult and management can indeed effectively substitute for a physical face-to-face encounter.

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Peripheral primitive neuroectodermal tumor of cauda equina: A report and review of literature

A Ajaya Kumar, Shaikhali Barodawala

Neurology India 2018 66(3):850-852



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Training residents and fellows in the procedure of diagnostic cervicocerebral angiography: Techniques to avoid complications

Xianli Lv, Wei Li, Youxiang Li

Neurology India 2018 66(3):652-656

We examine the problems arising when training residents/fellows (RFs) initiate the learning of diagnostic cervicocerebral angiography (DCCA) and describe the steps on how to facilitate the learning process while avoiding complications. The risk of permanent neurological deficit as a result of DCCA ranges from 0.3–0.5%. Factors that correlated with complications include the following: the history of cerebral infarction, infusion of a large amount of contrast medium, a prolonged fluoroscopic time (>80 min) and the efficiency of training received. These findings suggest that the neurological morbidity depends largely upon the technique of catheterization of the patient. In order to reduce the complications arising from the lack of training, a personalised mentorship with a careful supervision of trainees is necessary. To ensure a good patient outcome, a decreased procedural time, awareness of complications at every step of the procedure and their avoidance, as well as the provision of good quality images is necessary. A mentorship program with a close supervision of the RFs is also one of the prerequisites for obtaining a good result.

https://ift.tt/2IlrR8Y

Primary cerebellar agenesis in a normal man

Shah Omair, Wani Arif, Bashir Muiez, Suhail Jan, Dar Musaib, Gojwari Tariq

Neurology India 2018 66(3):871-873



https://ift.tt/2IGXgWK

Parent vessel occlusion and revascularization: A dying art?

Paritosh Pandey

Neurology India 2018 66(3):657-660



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What is the current role of bypass surgery in the management of cerebral aneurysms?

Laligam N Sekhar, Chun-Yu Cheng, Harley Brito Da Silva, Zeeshan Qazi

Neurology India 2018 66(3):661-663



https://ift.tt/2IqGN5H

Craniovertebral junction evaluation by computed tomography in asymptomatic individuals in the Indian population

Chinmaya Dash, Raghav Singla, Mohit Agarwal, Ambuj Kumar, Hitesh Kumar, Shashwat Mishra, Bhawani S Sharma

Neurology India 2018 66(3):797-803

Background: The available literature on the anatomy and imaging of the craniovertebral junction (CVJ) focusses on the osteometric indices described for the detection of abnormal relationships between the components of CVJ. However, a knowledge of the normal osteometry of this region in the Indian population is critically important for the operating surgeon as it may influence the surgical technique as well as the choice, size and configurations of the implants. It is also important to determine whether critical differences exist between the osteometric data of Indians and the rest of the world for this part of the anatomy. Accordingly, the present study is an attempt to quantitate the osteometric indices for the anatomically normal CVJ in Indian subjects Materials and Methods: We retrospectively studied the imaging data of 49 consecutive adult patients (31 males, 18 females) who underwent a computed tomographic (CT) angiogram for suspected vascular conditions unrelated to the craniovertebral junction. Several parameters related to the atlanto-dental relationship, foramen magnum, atlas and axis vertebrae were recorded, including the dimensions of the commonly instrumented bony regions and also the indices related to the CVJ bony relationships. The data was also compared between the two genders, statistically through the Student's t-test using the statistical program "R". Results: No patient had an atlanto dens interval >2.5 mm. The mean distance of the odontoid tip from the McRae line in this series was 5.11 mm and no patient had the odontoid tip above the McRae line. Female subjects had significantly smaller diameters of C1 lateral masses and odontoid screw trajectory length when compared to males. Additionally, in the Indian population, the length range of odontoid screw trajectory and the thickness of the narrowest part of the C2 pedicles was smaller with respect to similar data from other geographical regions. However, the rest of the parameters resembled the data from studies conducted on populations with other ethnicities. Conclusion: The osteometric parameters of the CVJ in the Indian population are largely similar to those described globally. However, there are some important differences too which can influence the design of surgical implants suited to the Indian population.

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High time we focus on sleep in amyotrophic lateral sclerosis!

Garima Shukla, Anupama Gupta

Neurology India 2018 66(3):664-665



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Methamphetamine-induced internal carotid artery vasospasm: A rapidly fatal stroke

Chen Fei Ng, Chia Yin Chong

Neurology India 2018 66(3):826-827



https://ift.tt/2IMPKd7

Adsorption performance and mechanism of magnetic reduced graphene oxide in glyphosate contaminated water

Abstract

In this study, the magnetic reduced graphene oxide (RGO/Fe₃O₄), with easy separation and high adsorption performance, was prepared and used to treat glyphosate (GLY) contaminated water. GLY adsorption performance of RGO/Fe₃O₄ was investigated, and influences of pH, adsorption time, temperature, contaminant concentration, and competing anions were analyzed. Moreover, the adsorption mechanism was discussed in the light of several characterization methods, including scanning electron microscopy (SEM), energy dispersive spectrum (EDS), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). The results demonstrated that the RGO/Fe₃O₄ presented a significant GLY adsorption capacity and acid condition was beneficial for this adsorption. The pseudo-second-order kinetic model and the Langmuir model correlated satisfactorily to the experimental data, indicating that this process was controlled by chemical adsorption and monolayer adsorption. Thermodynamic studies revealed that the adsorption of glyphosate onto RGO/Fe₃O₄ was spontaneous, endothermic, and feasible process. High temperatures were beneficial to GLY adsorption. The GLY adsorption mechanism of RGO/Fe₃O₄ was mainly attributed to hydrogen-bond interaction, electrostatic interaction, and coordination. Therefore, the RGO/Fe₃O₄ investigated in this research may offer an attractive adsorbent candidate for treatment of glyphosate contaminated water and warrant further study as a mechanism for glyphosate efficient removal.

https://ift.tt/2GkrRny

Effects of fouling on separation performance by forward osmosis: the role of specific organic foulants

Abstract

In this study, forward osmosis (FO) membranes and fouling solutions were systematically characterized to elucidate the effects of organic fouling on the rejection of two pharmaceutically active compounds, namely, sulfamethoxazole and carbamazepine. Municipal wastewater resulted in a more severe flux decline compared to humic acid and sodium alginate fouling solutions. This result is consistent with the molecular weight distribution of these foulant solutions. Liquid chromatography with organic carbon detection analysis shows that municipal wastewater consists of mostly low molecular weight acids and neutrals, which produce a more compact cake layer on the membrane surface. By contrast, humic acid and sodium alginate consist of large molecular weight humic substances and biopolymers, respectively. The results also show that membrane fouling can significantly alter the membrane surface charge and hydrophobicity as well as the reverse salt flux. In particular, the reverse salt flux of a fouled membrane was significantly higher than that under clean conditions. Although the rejection of sulfamethoxazole and carbamazepine by FO membrane was high, a discernible impact of fouling on their rejection could still be observed. The results show that size exclusion is a major rejection mechanism of both sulfamethoxazole and carbamazepine. However, they respond to membrane fouling differently. Membrane fouling results in an increase in sulfamethoxazole rejection while carbamazepine rejection decreases due to membrane fouling.

https://ift.tt/2L0X0jw

Progesterone Receptor Regulation of Uterine Adaptation for Pregnancy

Publication date: Available online 25 April 2018
Source:Trends in Endocrinology & Metabolism
Author(s): San-Pin Wu, Rong Li, Francesco J. DeMayo
Progesterone acts through the progesterone receptor to direct physiological adaption of the uterus in preparation and completion of pregnancy. Genome-wide transcriptome and cistrome analyses have uncovered new members and novel modifiers of the progesterone signaling pathway. Genetically engineered mice allow functional assessment of newly identified genes in vivo and provide insights on the impact of progesterone receptor-dependent molecular mechanisms on pregnancy at the organ system level. Progesterone receptor isoforms collectively mediate progesterone signaling via their distinct and common downstream target genes, which makes the stoichiometry of isoforms relevant in modifying the progesterone activity. This review discusses recent advances on the discovery of the progesterone receptor network, with special focus on the endometrium at early pregnancy and myometrium during parturition.



https://ift.tt/2IkYRSO

Editorial Board and Contents

Publication date: June 2018
Source:Trends in Endocrinology & Metabolism, Volume 29, Issue 6





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A Novel Regulator of Type II Diabetes: MicroRNA-143

Publication date: June 2018
Source:Trends in Endocrinology & Metabolism, Volume 29, Issue 6
Author(s): Biao Li, Jingjing Fan, Ning Chen
MiR-143 is an miRNA with the function of specifically inhibiting the insulin-AKT pathway via the downregulation of oxysterol-binding protein-related protein 8 (ORP8), thus resulting in the inhibition of AKT phosphorylation, insulin tolerance, and final development of type II diabetes mellitus (T2DM). Aerobic exercise can prevent T2DM by downregulating miR-143. However, the underlying mechanisms for exercise-induced change of miR-143 remain unclear. In the present study, we will summarize the involvement of miR-143 in regulating the development of T2DM and the underlying mechanisms for potential diagnosis, prevention, and treatments, including exercise intervention for T2DM by targeting miR-143.



https://ift.tt/2IjFWHW

Does This Schlank Make Me Look Fat?

Publication date: Available online 21 April 2018
Source:Trends in Endocrinology & Metabolism
Author(s): Bhagirath Chaurasia, William L. Holland, Scott A. Summers
Chaurasia and colleagues discuss the provocative new finding that some enzymes in the de novo sphingolipid synthesis pathway have dual roles as transcriptional regulators.



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Advances in the Molecular Pathophysiology, Genetics, and Treatment of Primary Ovarian Insufficiency

Publication date: June 2018
Source:Trends in Endocrinology & Metabolism, Volume 29, Issue 6
Author(s): Ilpo Huhtaniemi, Outi Hovatta, Antonio La Marca, Gabriel Livera, Danielle Monniaux, Luca Persani, Abdelkader Heddar, Katarzyna Jarzabek, Triin Laisk-Podar, Andres Salumets, Juha S. Tapanainen, Reiner A. Veitia, Jenny A. Visser, Peter Wieacker, Slawomir Wolczynski, Micheline Misrahi
Primary ovarian insufficiency (POI) affects ∼1% of women before 40 years of age. The recent leap in genetic knowledge obtained by next generation sequencing (NGS) together with animal models has further elucidated its molecular pathogenesis, identifying novel genes/pathways. Mutations of >60 genes emphasize high genetic heterogeneity. Genome-wide association studies have revealed a shared genetic background between POI and reproductive aging. NGS will provide a genetic diagnosis leading to genetic/therapeutic counseling: first, defects in meiosis or DNA repair genes may predispose to tumors; and second, specific gene defects may predict the risk of rapid loss of a persistent ovarian reserve, an important determinant in fertility preservation. Indeed, a recent innovative treatment of POI by in vitro activation of dormant follicles proved to be successful.



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Molecular Mechanisms Governing Embryonic Differentiation of Pituitary Somatotropes

Publication date: Available online 11 May 2018
Source:Trends in Endocrinology & Metabolism
Author(s): Buffy S. Ellsworth, Caitlin E. Stallings
Pituitary somatotropes secrete growth hormone (GH), which is essential for normal growth and metabolism. Somatotrope defects result in GH deficiency (GHD), leading to short stature in childhood and increased cardiovascular morbidity and mortality in adulthood. Current hormone replacement therapies fail to recapitulate normal pulsatile GH secretion. Stem cell therapies could overcome this problem but are dependent on a thorough understanding of somatotrope differentiation. Although several transcription factors, signaling pathways, and hormones that regulate this process have been identified, the mechanisms of action are not well understood. The purpose of this review is to highlight the known players in somatotrope differentiation while emphasizing the need to better understand these pathways to serve patients with GHD.



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Atherosclerosis Is an Epigenetic Disease

Publication date: Available online 10 May 2018
Source:Trends in Endocrinology & Metabolism
Author(s): Suowen Xu, Jaroslav Pelisek, Zheng Gen Jin
Atherosclerosis is a chronic inflammatory and lipid-depository disease that eventually leads to acute cardiovascular events. Emerging evidence supports that epigenetic processes such as DNA methylation, histone modification, and noncoding RNAs play an important role in plaque progression and vulnerability, highlighting the therapeutic potential of epigenetic drugs in cardiovascular therapeutics.



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GABAergic Signaling Mediates Central Cardiovascular Angiotensin II Type 2 Receptor Effects

Publication date: Available online 5 May 2018
Source:Trends in Endocrinology & Metabolism
Author(s): Laura Légat, Ilse Smolders, Alain G. Dupont




https://ift.tt/2wK0UKD

Fine-Tuning Mitochondrial Dysfunction and Reductive Carboxylation

Publication date: Available online 23 April 2018
Source:Trends in Endocrinology & Metabolism
Author(s): Christopher J. Halbrook, Zeribe C. Nwosu, Costas A. Lyssiotis
Metabolic processes within cells are dynamically interconnected. If mitochondria become defective, cells must rewire their metabolism to survive. Here we highlight recent work by Gaude et al. that used a tunable model of mitochondrial dysfunction combined with metabolic tracing and in silico analyses to define these compensatory pathways.



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Hippo Signaling: Key Emerging Pathway in Cellular and Whole-Body Metabolism

Publication date: Available online 5 May 2018
Source:Trends in Endocrinology & Metabolism
Author(s): Amin Ardestani, Blaz Lupse, Kathrin Maedler
The evolutionarily conserved Hippo pathway is a key regulator of organ size and tissue homeostasis. Its dysregulation is linked to multiple pathological disorders. In addition to regulating development and growth, recent studies show that Hippo pathway components such as MST1/2 and LATS1/2 kinases, as well as YAP/TAZ transcriptional coactivators, are regulated by metabolic pathways and that the Hippo pathway controls metabolic processes at the cellular and organismal levels in physiological and metabolic disease states such as obesity, type 2 diabetes (T2D), nonalcoholic fatty liver disease (NAFLD), cardiovascular disorders, and cancer. In this review we summarize the connection between key Hippo components and metabolism, and how this interplay regulates cellular metabolism and metabolic pathways. The emerging function of Hippo in the regulation of metabolic homeostasis under physiological and pathological conditions is highlighted.



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miR-33: A Metabolic Conundrum

Publication date: Available online 21 April 2018
Source:Trends in Endocrinology & Metabolism
Author(s): Anders M. Näär
The miR-33 microRNAs (miRNAs) are crucial regulators of cholesterol/lipids, and may represent therapeutic targets for the treatment of atherosclerosis. A recent report by Price et al. showed that miR-33 knockout (KO) mice exhibit obesity, insulin resistance, and increased food intake, suggesting that metabolic regulation by miR-33 is more complex than was previously known.



https://ift.tt/2IiInup

Editorial Board and Contents

Publication date: May 2018
Source:Trends in Endocrinology & Metabolism, Volume 29, Issue 5





https://ift.tt/2KslAZs

Autologous Liquid Platelet Rich Fibrin: a novel drug delivery system

Publication date: Available online 15 May 2018
Source:Acta Biomaterialia
Author(s): Richard J Miron, Yufeng Zhang
There is currently widespread interest within the biomaterial field to locally deliver biomolecules for bone and cartilage regeneration. Substantial work to date has focused on the potential role of these biomolecules during the healing process, and the carrier system utilized is a key factor in their effectiveness. Platelet rich fibrin (PRF) is a naturally derived fibrin scaffold that is easily obtained from peripheral blood following centrifugation. Slower centrifugation speeds have led to the commercialization of a liquid formulation (liquid-PRF) resulting in an upper plasma layer composed of liquid fibrinogen/thrombin prior to clot formation that remains in its liquid phase for approximately 15 minutes until injected into bodily tissues. Herein, we introduce the use of liquid PRF as an advanced local delivery system for small and large biomolecules. Potential target molecules including large (growth factors/cytokines and morphogenetic/angiogenic factors), as well as small (antibiotics, peptides, gene therapy and anti-osteoporotic) molecules are considered potential candidates for enhanced bone/cartilage tissue regeneration. Furthermore, liquid-PRF is introduced as a potential carrier system for various cell types and nano-sized particles that are capable of limiting/by-passing the immune system and minimizing potential foreign body reactions within host tissues following injection.statement of significanceThere is currently widespread interest within the biomaterial field to locally deliver biomolecules for bone and cartilage regeneration. This review article focuses on the use of a liquid version of platelet rich fibrin (PRF) composed of liquid fibrinogen/thrombin as a drug delivery system. Herein, we introduce the use of liquid PRF as an advanced local delivery system for small and large biomolecules including growth factors, cytokines and morphogenetic/angiogenic factors, as well as antibiotics, peptides, gene therapy and anti-osteoporotic molecules as potential candidates for enhanced bone/cartilage tissue regeneration.

Graphical abstract

https://ift.tt/2IlS4nF

An integrated biomanufacturing platform for the large-scale expansion and neuronal differentiation of human pluripotent stem cell-derived neural progenitor cells

Publication date: Available online 15 May 2018
Source:Acta Biomaterialia
Author(s): Gayathri Srinivasan, Daylin Morgan, Divya Varun, Nicholas Brookhouser, David A. Brafman
Human pluripotent stem cell derived neural progenitor cells (hNPCs) have the unique properties of long-term in vitro expansion as well as differentiation into the various neurons and supporting cell types of the central nervous system (CNS). Because of these characteristics, hNPCs have tremendous potential in the modeling and treatment of various CNS diseases and disorders. However, expansion and neuronal differentiation of hNPCs in quantities necessary for these applications is not possible with current two dimensional (2-D) approaches. Here, we used a fully defined peptide substrate as the basis for a microcarrier (MC)-based suspension culture system. Several independently derived hNPC lines were cultured on MCs for multiple passages as well as efficiently differentiated to neurons. Finally, this MC-based system was used in conjunction with a low shear rotating wall vessel (RWV) bioreactor for the integrated, large-scale expansion and neuronal differentiation of hNPCs. Overall, this fully defined and scalable biomanufacturing system will facilitate the generation of hNPCs and their neuronal derivatives in quantities necessary for basic and translational applications.Statement of significanceIn this work, we developed a microcarrier (MC)-based culture system that allows for the expansion and neuronal differentiation of human pluripotent stem cell-derived neural progenitor cells (hNPCs) under defined conditions. In turn, this MC approach was implemented in a rotating wall vessel (RWV) bioreactor for the large-scale expansion and neuronal differentiation of hNPCs. This work is of significance as it overcomes current limitations of conventional two dimensional (2-D) culture systems to enable the generation of hNPCs and their neuronal derivatives in quantities required for downstream applications in disease modeling, drug screening, and regenerative medicine.

Graphical abstract

https://ift.tt/2k0D5ow

Biosafety, stability, and osteogenic activity of novel implants made of Zr70Ni16Cu6Al8 bulk metallic glass for biomedical application

Publication date: Available online 15 May 2018
Source:Acta Biomaterialia
Author(s): Hiroto Ida, Masahiro Seiryu, Nobuo Takeshita, Masanari Iwasaki, Yoshihiko Yokoyama, Yusuke Tsutsumi, Etsuko Ikeda, Satoshi Sasaki, Shunro Miyashita, Shutaro Sasaki, Tomohiro Fukunaga, Toru Deguchi, Teruko Takano-Yamamoto
Superior mechanical and chemical properties of Zr70Ni16Cu6Al8 bulk metallic glass (BMG) demonstrate its promise as a novel biomaterial for fabrication of implants. The aim of the present study was to validate mechanical, chemical, and biological properties of Zr70Ni16Cu6Al8 BMG through comparison with titanium (Ti). Our data indicated higher tensile strength, lower Young's modulus, and reduced metal ion release of Zr70Ni16Cu6Al8 BMG compared with Ti. Biosafety of bone marrow mesenchymal cells on Zr70Ni16Cu6Al8 BMG was comparable to that of Ti. Next, screw-type implant prototypes made of Zr70Ni16Cu6Al8 BMG were fabricated and inserted into rat long bones. Zr70Ni16Cu6Al8 BMG implants indicated a higher removal-torque value and lower Periotest value compared with Ti implants. In addition, higher amounts of new bone formation and osseointegration were observed around Zr70Ni16Cu6Al8 BMG implants compared with Ti implants. Moreover, gene expression analysis displayed higher expression of osteoblast- and osteoclast-associated genes in the Zr70Ni16Cu6Al8 BMG group compared with the Ti group. Importantly, loading to implants upregulated bone formation, as well as osteoblast- and osteoclast-associated gene expression in the peri-implant area. No significant difference in concentrations of Ni, Al, Cu, and Zr in various organs was shown between in the Zr70Ni16Cu6Al8 BMG and Ti groups. Collectively, these findings suggest that Zr70Ni16Cu6Al8 BMG is suitable for fabricating novel implants with superior mechanical properties, biocompatibility, stability, and biosafety compared with Ti.Statement of significanceTitanium is widely used to fabricate orthopedic and dental implants. However, Titanium has disadvantages for biomedical applications in regard to strength, elasticity, and biosafety. Recently, we developed a novel hypoeutectic Zr70Ni16Cu6Al8 BMG, which has superior mechanical and chemical properties. However, the validity of Zr70Ni16Cu6Al8 BMG for biomedical application has not been cleared.The aim of the present study was to validate the mechanical, chemical, and biological properties of Zr70Ni16Cu6Al8 BMG for biomedical applications through comparison with Titanium. The present study clarifies that Zr70Ni16Cu6Al8 BMG has good mechanical properties, corrosion resistance, and osteogenic activity, which are necessary features for biomedical applications. The present study provides for the first time the superiority of Zr70Ni16Cu6Al8 BMG implants to Titanium implants for biomedical applications.

Graphical abstract

https://ift.tt/2IqzA5D

IgG4-Associated Adrenalis—a Case Report

Abstract

A 67-year-old man was adrenalectomized due to a tumor measuring 100 mm. Specimens revealed an inflammation with slight fibrosis and moderate infiltrates of lymphocytes and plasmacytes with immunoreactivity for IgG and IgG4 resulting in the diagnosis of an active IgG4-associated adrenalitis. To our knowledge, this is the first reported active adrenalitis of this type. It should be the precursor lesion of the adrenal calcifying fibrous tumor that was reported once before.

https://ift.tt/2KnA4dl

Prestimulus delta and theta contributions to equiprobable Go/NoGo processing in healthy ageing

Publication date: Available online 15 May 2018
Source:International Journal of Psychophysiology
Author(s): Frances M. De Blasio, Robert J. Barry
Ongoing EEG activity contributes to ERP outcomes of stimulus processing, and each of these measures is known to undergo (sometimes significant) age-related change. Variation in their relationship across the life-span may thus elucidate mechanisms of normal and pathological ageing. This study assessed the relationships between low-frequency EEG prestimulus brain states, the ERP, and behavioural outcomes in a simple equiprobable auditory Go/NoGo paradigm, comparing these for 20 young (Mage = 20.4 years) and 20 healthy older (Mage = 68.2 years) adults. Prestimulus delta and theta amplitudes were separately assessed; these were each dominant across the midline region, and reduced in the older adults. For each band, (within-subjects) trials were sorted into ten increasing prestimulus EEG levels for which separate ERPs were derived. The set of ten ERPs for each band-sort was then quantified by PCA, independently for each group (young, older adults). Four components were primarily assessed (P1, N1-1, P2/N2b complex, and P3), with each showing age-related change. Mean RT was comparable, but intra-individual RT variability increased in older adults. Prestimulus delta and theta each generally modulated component positivity, indicating broad influence on task processing. Prestimulus delta was primarily associated with the early sensory processes, and theta more with the later stimulus-specific processes; prestimulus theta also inversely modulated intra-individual RT variability across the groups. These prestimulus EEG–ERP dynamics were consistent between the young and older adults in each band for all components except the P2/N2b, suggesting that across the lifespan, Go/NoGo categorisation is differentially affected by prestimulus delta and theta.



https://ift.tt/2wGuVv2

The role of heat shock protein 70 in oxidant stress and inflammatory injury in quail spleen induced by cold stress

Abstract

The aim of this study was to investigate the role of heat shock protein 70 (Hsp70) in oxidative stress and inflammatory damage in the spleen of quails which were induced by cold stress. One hundred ninety-two 15-day-old male quails were randomly divided into 12 groups and kept at 12 ± 1 °C to examine acute and chronic cold stress. We first detected the changes in activities of antioxidant enzymes in the spleen tissue under acute and chronic cold stress. The activities of glutathione peroxidase (GSH-Px) fluctuated in acute cold stress groups, while they were significantly decreased (p < 0.05) after chronic cold stress. The activities of superoxide dismutase (SOD), inducible nitric oxide synthase (iNOS), and nitric oxide (NO) content were decreased significantly (p < 0.05) in both of the acute and chronic cold stress groups. Malondialdehyde (MDA) content was significantly increased (p < 0.05) under cold stress except the 0.5 h group of acute cold stress. Besides, histopathological analysis showed that quail's spleen tissue was inflammatory injured seriously in both the acute and chronic cold stress groups. Additionally, the inflammatory factors (cyclooxygenase-2 (COX-2), prostaglandin E synthase (PTGES), iNOS, nuclear factor-kappa B (NF-κB), and tumor necrosis factor-a (TNF-α)) and Hsp70 mRNA levels were increased in both of the acute and chronic cold stress groups compared with the control groups. These results suggest that oxidative stress and inflammatory injury could be induced by cold stress in spleen tissues of quails. Furthermore, the increased expression of Hsp70 may play a role in protecting the spleen against oxidative stress and inflammatory damage caused by cold stress.

https://ift.tt/2k0lMnP

Comparative study on adsorption of crude oil and spent engine oil from seawater and freshwater using algal biomass

Abstract

Efficiency of a biosorbent prepared from the green macroalga Enteromorpha intestinalis biomass for decontamination of seawater and freshwater polluted by crude oil and engine spent oil was compared. The effect of different experimental conditions including contact time, pH, particle size, initial oil concentration, and biosorbent dose on the oil biosorption was studied in the batch method. The biosorbent was characterized by CHNOS, FTIR, and SEM analysis. The experimental data were well fitted to the pseudo-second-order kinetic model and the Langmuir adsorption isotherm model. Based on the obtained results, the adsorption of spent oil with higher viscosity was better than crude oil. The biosorption of oil hydrocarbons from seawater was more efficient than freshwater. The algal biomasses which are abundantly available could be effectively used as a low-cost and environmentally friendly adsorbent for remediation of oil spill in the marine environments or in the water and wastewater treatment.

https://ift.tt/2wHtsEB

Cl-initiated photo-oxidation reactions of methyl propionate in atmospheric condition

Abstract

Cl-initiated photo-oxidation reaction of methyl propionate was investigated experimentally using relative rate method. Gas chromatography/mass spectrometry (GC-MS) and GC/infrared spectroscopy (GC-IR) were used as analytical tools to follow the concentrations of reactants and products during reaction. The gas-phase kinetics of methyl propionate with Cl atoms was measured over the temperature range of 263–363 K at 760 Torr in N₂ atmosphere using C₂H₆ and C₂H₄ as reference compounds. The temperature-dependent rate coefficient for the reaction of methyl propionate with Cl atom was obtained as k(T) = [(3.25 ± 1.23) × 10⁻¹⁶] T² exp [− (33 ± 4) / T] cm³ molecule⁻¹ s⁻¹. Theoretical calculations were also performed at CCSD(T)/cc-pVDZ//B3LYP/6-31G(d,p) level of theory, and the rate coefficients for H abstraction reactions were evaluated using canonical variational transition state theory (CVT/SCT) with interpolated single point energy (ISPE) method over the temperature range of 200–400 K. The rate coefficients over the studied temperature range yielded the Arrhenius expression k(T) = (7.22 × 10⁻¹⁶) T^1.5 exp (466 / T) cm³ molecule⁻¹ s⁻¹. The reaction mechanism based on product analysis, thermochemistry, branching ratios, atmospheric implications, degradation pathways, and cumulative lifetime of methyl propionate is also presented in this manuscript.

Graphical abstract

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https://ift.tt/2rJnQEN

A wavelength-modulated localized surface plasmon resonance (LSPR) optical fiber sensor for sensitive detection of mercury(II) ion by gold nanoparticles-DNA conjugates

Publication date: 30 August 2018
Source:Biosensors and Bioelectronics, Volume 114
Author(s): Shuo Jia, Chao Bian, Jizhou Sun, Jianhua Tong, Shanhong Xia
The study presented herein investigated an easy preparation, high performance, wavelength-modulated LSPR optical fiber chemosensor coated by gold nanospheres(AuNS) for Hg²⁺ detection based on thymine-Hg²⁺-thymine base pair mismatches and the coupled plasmonic resonance effect.Utilizing electrostatic self-assembly method, the high density and dispersivity monolayer AuNS coated LSPR fiber sensor had the near field refractive index sensitivity up to 2016 nm/RIU. The single-strand probe DNA served as a binding element for free AuNS labelled-target DNA conjugates was attached to the monolayer AuNS by Au-S bond. In the present of Hg²⁺, the coupled plasmonic resonance band between monolayer AuNS and free AuNS was produced by thymine-Hg²⁺-thymine structure and leaded to red-shift of LSPR peak. Under the optimal conditions, the enlarged red-shift in peak of LSPR spectroscopy was linearly with the concentration of Hg²⁺ in the range from 1.0 × 10⁻⁹ to 5.0 × 10⁻⁸ M with the coefficient of 0.976. The limit of detection was 0.7 nM(S/N = 3). The specificity of the sensor was proved high by evaluating the response to other heavy metal ions. The proposed fiber sensor provided a label-free, miniature, low-cost approach for the Hg²⁺ detection and had potential in real environmental evaluations.



https://ift.tt/2KrWkTq

Dual-core all-fiber integrated immunosensor for detection of protein antigens

Publication date: 30 August 2018
Source:Biosensors and Bioelectronics, Volume 114
Author(s): Karol Wysokiński, Dawid Budnicki, Janusz Fidelus, Łukasz Szostkiewicz, Łukasz Ostrowski, Micha Murawski, Marcin Staniszewski, Magdalena Staniszewska, Marek Napierała, Tomasz Nasiłowski
An optical fiber interferometric microprobe for detection of specific proteins is presented in this paper. The microprobe is an all-fiber device, which is based on Michelson interferometer configuration, which allows for detection of protein antigens in an analyzed solution thanks to antibodies immobilized on the sensor surface. The interferometer is made of dual core fiber and has a precisely formed arm length difference, achieved by splicing a fragment of polarization maintaining fiber to one of the cores. An all-fiber configuration of the sensor decreases substantially cross-sensitivities to temperature and deformation in comparison to other optical fiber interferometers. Reported sensor has a sensing region on the tip of the interferometer and therefore may be used for point measurements in medicine. The immunosensor and optical measuring system are designed to utilize the most common broadband light sources that operate at a central wavelength of 1.55 µm. The results show that it is possible to detect a protein antigen present in a solution by using an all-fiber interferometer coated with specific antibodies. The resulting peak shift can reaches 0.6 nm, which is sufficient to be measured by an optical spectrum analyzer or a spectrometer. A model allowing for estimation of the value of lower limit of detection for such sensors has been elaborated. The elaborated detection system may act as a framework for detection of various antigens and thus it can find future applications in medical diagnostics.



https://ift.tt/2IiZeNu

A simple ultrasensitive electrochemical sensor for simultaneous determination of gallic acid and uric acid in human urine and fruit juices based on zirconia-choline chloride-gold nanoparticles-modified carbon paste electrode

Publication date: 30 August 2018
Source:Biosensors and Bioelectronics, Volume 114
Author(s): Seyed Alireza Shahamirifard, Mehrorang Ghaedi, Zahra Razmi, Shaaker Hajati
The determination of gallic acid (GA) and uric acid (UA) is essential due to their biological properties. Numerous methods have been reported for the analysis of GA and UA in various real samples. However, the development of a simple, rapid and practical sensor still remains a great challenge. Here, a carbon paste electrode (CPE) was modified by nanocomposite containing zirconia nanoparticles (ZrO2NPs), Choline chloride (ChCl) and gold nanoparticles (AuNPs) to construct ZrO2-ChCl-AuNPs/CPE as electrochemical sensor for the simultaneous electro-oxidation of GA and UA. Characterization was performed by Fourier transform infrared spectroscopy, X-ray diffraction, field emission scanning electron microscopy and energy dispersive X-ray spectroscopy. The modified electrode was investigated by different methods including electrochemical impedance spectroscopy and cyclic voltammetry. Kinetic parameters such as charge transfer coefficient, standard heterogeneous electron transfer rate constant and other parameters were calculated via voltammetry techniques. Differential pulse voltammetry was used for simultaneous determination of GA and UA applying the ZrO2-ChCl-AuNPs/CPE electrode. At the optimum conditions, this sensor showed a linear response in the ranges 0.22– 55 and 0.12–55 µM for GA and UA, respectively. In addition, low detection limits of 25 and 15 nM were obtained for GA and UA, respectively. Furthermore, ZrO2-ChCl-AuNPs/CPE was successfully applied for the independent determination of GA in green tea and fruit juice as well as the simultaneous determination of GA and UA in human urine samples.



https://ift.tt/2KrW7j6

An ultrasensitive electrochemiluminescence biosensor for detection of MicroRNA by in-situ electrochemically generated copper nanoclusters as luminophore and TiO2 as coreaction accelerator

Publication date: 30 August 2018
Source:Biosensors and Bioelectronics, Volume 114
Author(s): Hongxia Liao, Ying Zhou, Yaqin Chai, Ruo Yuan
Herein, we constructed an ultrasensitive electrochemiluminescence (ECL) biosensor for detecting microRNA-21 (miR-21) based on in-situ generation of copper nanoclusters (Cu NCs) as luminophore and titanium dioxide (TiO2) as coreaction accelerator. First, numerous AT-rich double-stranded DNA (dsDNA) was produced from the conversion of a small amount of target miR-21 via the combination of exonuclease III (Exo III)-assisted amplification and hybridization chain reaction (HCR), which could reduce the aggregation-caused self-etching effect of Cu NCs and improve the emitting of Cu NCs. Simultaneously, the introduction of TiO2 in the sensing interface not just acted as the immobilizer of dsDNA-stabilized Cu NCs, more than acted as the coreaction accelerator to accelerate the reduction of the coreaction reagent (S2O8²⁻) for significantly enhancing the ECL efficiency of Cu NCs. The biosensor showed an excellent linear relationship in the concentration range from 100 aM to 100 pM with the detection limit of 19.05 aM Impressively, the strategy not only opened up a novel and efficient preparation method for the Cu NCs, but expanded the application of Cu NCs in ultrasensitive biodetection owing to the addition of coreaction accelerator.



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Biomimetic magnetoelectric nanocrystals synthesized by polymerization of heme as advanced nanomaterials for biosensing application

Publication date: 30 August 2018
Source:Biosensors and Bioelectronics, Volume 114
Author(s): Jeong Eun Hyeon, Da Woon Jeong, Young Jin Ko, Seung Wook Kim, Chulhwan Park, Sung Ok Han
Regardless of the malaria disease risk, the malaria parasite Plasmodium falciparum has an interesting mechanism. During its growth within the red blood cell, toxic free heme is converted into an insoluble crystalline form called the malaria pigment, or hemozoin. In particular, natural hemozoin nanocrystals can provide multiple applications in biosensing fields for health care and diagnosis as similar to artificial metal nanoparticles. In this study, the heme was biologically synthesized and polymerized by Corynebacterium glutamicum and final polymer was applied as a biomimetic conductive biopolymer. The biosynthesized monomer heme by metabolic engineered strain was enzymatically polymerized by an enzyme complex containing two different heme polymerization proteins. Moreover, the electrical conductivities of hemozoin prepared by heme polymerase enzyme complexes were investigated and compared with those of the heme monomer. Because of the synergetic effects of polymerized heme, synthesized artificial nanocrystals exhibited a greater conductive property than a heme monomer. As a result of their surpassing properties, developed novel magnetoelectric nanocrystals could be motivated as smaller scale electronic devices with advanced properties. Thus, these results will open a brand new field in the frontier of the heme detoxification mechanism of the malaria parasite and its biomimetic application as advanced nanomaterials for biological and biomedical sensing.

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Understanding one’s body and movements from the perspective of young adults with autism: A mixed-methods study

Publication date: July 2018
Source:Research in Developmental Disabilities, Volume 78
Author(s): Ingrid Bertilsson, Amanda Lundvik Gyllensten, Arve Opheim, Gunvor Gard, Catharina Sjödahl Hammarlund
BackgroundThere are but a few studies of how persons with autism perceive their bodies and movements. Difficulties in perceiving the surrounding world along with disturbed motor coordination and executive functions may affect physical and psychological development.AimsTo explore the experiences of body and movements in young adults with autism and how two physiotherapeutic instruments may capture these experiences.ProceduresEleven young adults (16–22 years) with autism were interviewed and assessed using Bruininks-Oseretsky Test of Motor Proficiency (BOT2) and Body Awareness Scale Movement Quality and Experience (BAS MQ-E). Following a mixed- methods design, the interviews were deductively analyzed and conceptually integrated to the results of the two assessments.ResultsExperiencing conflicting feelings about their bodies/movements, led to low understanding of themselves. The assessments captured these experiences relatively well, presenting both movement quality and quantity. Positive experiences and better movement quality related to having access to more functional daily strategies.ConclusionCombining motor proficiency and body awareness assessments was optimal to understand the participants' experiences.ImplicationsTo capture body and movement functions in persons with autism in this standardized manner will lead to improved and reliable diagnoses, tailored interventions, increased body awareness and activity, and enhanced quality of life.



https://ift.tt/2rKZWYW

Solid waste management of small island developing states—the case of the Seychelles: a systemic and collaborative study of Swiss and Seychellois students to support policy

Abstract

Solid waste management (SWM) is a significant challenge for the Seychelles. Waste generation, fueled by economic development and tourism, increases steadily, while landfilling continues to be the main disposal path, thus exacerbating the island nation's specific weaknesses. Due to the small scale of the Seychelles economy, there is little capital available to stimulate innovations in SWM and generate the knowledge for setting priorities and guiding SWM action. Students from ETH Zurich and UniSey conducted a transdisciplinary case study (tdCS) to fill this knowledge gap and gain insights into the obstacles and opportunities related to sustainable SWM. The tdCS approach allowed students to gain comprehensive and in-depth knowledge about the SWM system required to set priorities for action and next steps. The government should streamline the different financial frameworks according to a clear principle (e.g., polluter pays principle). Specific biogenic waste streams represent a potential source of energy and fertilizers. Expanding the scope and densifying the network of collection points could help raise recycling rates of other waste fractions. Diverting biogenic waste and recycling more glass, metals, paper, and plastics would also significantly reduce landfilling rates. Regardless of future amounts of waste ending up on landfills, the latter must be reengineered before the surrounding environment suffers major adverse impacts. All these actions imply a government-driven approach which integrates the views of stakeholders and consumers alike.

https://ift.tt/2wIa0rc

The indoor-outdoor characteristics of water-soluble ion in PM 2.5 in Tianjin wintertime

Abstract

The indoor and outdoor PM_2.5 mass concentration, water-soluble ion by filter sampler was analyzed on December 3–21, 2015 during wintertime in Tianjin, China. The results indicate that high humidity conditions result in the accumulation of atmospheric pollutants and reduce atmosphere visibility. The I/O ratio for PM_2.5 concentration in dormitory and lab are less than 1 in haze days. Indoor PM_2.5 concentration increases rapidly with outdoor PM_2.5 concentration increasing in haze days. The filtration factors of the dormitory and lab indicate nearly half of the outdoor PM_2.5 enters indoor environment. The human activities in dormitory could cause more the formation of PM_2.5 than those in lab. The concentration of SO₄²⁻ is the highest ion in water-soluble ion for outdoor PM_2.5. The SO₄²⁻, NO₃⁻, NH₄⁺, and Cl⁻ are generated mainly by outdoor sources; however, the Na⁺, Ca²⁺, and Mg²⁺ are generated mainly by indoor sources. The NH₄NO₃, (NH₄)₂SO₄, and NH₄Cl accounts for 20.2~41.8%, 32.0~51.4%, and 6.4~10.6% of the total water-soluble ion in different indoor-outdoor environment. The total secondary aerosols including NH₄NO₃, (NH₄)₂SO₄, and NH₄Cl in PM_2.5 are 28.3, 42.1, 28.2, 31.0, and 33.9% in outdoor environment for haze days, outdoor environment for non-haze days, dormitory for haze days, dormitory for non-haze days, and lab for haze days, respectively.

https://ift.tt/2rEGcab

Memory circuits: CA2

Publication date: October 2018
Source:Current Opinion in Neurobiology, Volume 52
Author(s): Rebecca A Piskorowski, Vivien Chevaleyre
The hippocampus is a central region in the coding of spatial, temporal and episodic memory. Recent discoveries have revealed surprising and complex roles of the small area CA2 in hippocampal function. Lesion studies have revealed that this region is required for social memory formation. Area CA2 is targeted by extra-hippocampal paraventricular inputs that release vasopressin and can act to enhance social memory performance. In vivo recordings have revealed nonconventional activity by neurons in this region that act to both initiate hippocampal sharp-wave ripple events as well as encode spatial information during immobility. Silencing of CA2 pyramidal neurons has revealed that this area also acts to control hippocampal network excitability during encoding, and this balance of excitation and inhibition is disrupted in disease. This review summarizes recent findings and attempts to integrate these results into pre-existing models.



https://ift.tt/2L19gAC

Neuronal coding mechanisms mediating fear behavior

Publication date: October 2018
Source:Current Opinion in Neurobiology, Volume 52
Author(s): Robert R Rozeske, Cyril Herry
The behavioral repertoire of an organism can be highly diverse, spanning from social to defensive. How an animal efficiently switches between distinct behaviors is a fundamental question whose inquiry will provide insights into the mechanisms that are necessary for an organism's survival. Previous work aimed at identifying the neural systems responsible for defensive behaviors, such as freezing, has demonstrated critical interactions between the prefrontal cortex and amygdala. Indeed, this foundational research has provided an indispensable anatomical framework that investigators are now using to understand the physiological mechanisms of defined neural circuits within the prefrontal cortex that code for the rapid and flexible expression of defensive behaviors. Here we review recent findings demonstrating temporal and rate coding mechanisms of freezing behavior in the prefrontal cortex. We hypothesize that anatomical features, such as target structure and cortical layer, as well as the nature of the information to be coded, may be critical factors determining the coding scheme. Furthermore, detailed behavioral analyses may reveal subtypes of defensive behaviors that represent the principle factor governing coding selection.



https://ift.tt/2GjdxM4

The neural circuits of thermal perception

Publication date: October 2018
Source:Current Opinion in Neurobiology, Volume 52
Author(s): Phillip Bokiniec, Niccolò Zampieri, Gary R Lewin, James FA Poulet
Thermal information about skin surface temperature is a key sense for the perception of object identity and valence. The identification of ion channels involved in the transduction of thermal changes has provided a genetic access point to the thermal system. However, from sensory specific 'labeled-lines' to multimodal interactive pathways, the functional organization and identity of the neural circuits mediating innocuous thermal perception have been debated for over 100 years. Here we highlight points in the system that require further attention and review recent advances using in vivo electrophysiology, cellular resolution calcium imaging, optogenetics and thermal perceptual tasks in behaving mice that have begun to uncover the anatomical principles and neural processing mechanisms underlying innocuous thermal perception.



https://ift.tt/2L2emMU

Gender- and age-varying associations of sensation seeking and substance use across young adulthood

Publication date: September 2018
Source:Addictive Behaviors, Volume 84
Author(s): Rebecca J. Evans-Polce, Megan S. Schuler, John E. Schulenberg, Megan E. Patrick
IntroductionSensation seeking is associated with elevated risk for substance use among adolescents and young adults. However, whether these associations vary across age for young men and women is not well characterized.MethodsUsing data from the Monitoring the Future (MTF) panel study, we examine the age-varying associations of sensation seeking and three types of substance use behavior (binge drinking, cigarette use, and marijuana use) across ages 18 to 30 using time-varying effect modeling. Analyses include participants in the eleven most recent MTF cohorts (12th-graders in 1994–2004), who are eligible to respond through age 29/30 (N = 6338 people; 30,237 observations).ResultsWhile sensation seeking levels and substance use are lower among women, the magnitude of the association of sensation seeking with binge drinking and with marijuana use among women exceeds that of men in the later 20s. Differential age trends were observed; among men, the associations generally decreased or remained constant with age. Yet among women, the associations decayed more slowly or even increased with age. Specifically, the association of sensation seeking with marijuana use among women increased during the late 20s, such that the association at age 30 exceeded that in the early 20s.ConclusionsThe significantly stronger associations of sensation seeking with binge drinking and marijuana use observed among women compared to men during the mid- to late-20s suggests divergent risk factors across genders for substance use during young adulthood, with sensation seeking remaining a strong risk factor for women but not men.



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Anti-inflammatory activities and potential mechanisms of phenolic acids isolated from Salvia miltiorrhiza f. alba roots in THP-1 macrophages

Publication date: 10 August 2018
Source:Journal of Ethnopharmacology, Volume 222
Author(s): Haimei Liu, Shuli Ma, Hongrui Xia, Hongxiang Lou, Faliang Zhu, Longru Sun
Ethnopharmacological relevanceThe roots of Salvia miltiorrhiza f. alba (Lamiaceae) (RSMA) are used as the Danshen, a traditional Chinese medicine, to treat the vascular diseases at local clinics, especially for the remedy of thromboangiitis obliterans (TAO) more than 100 years. Phenolic acids are one of the major effective constituents of RSMA, and some studies have linked phenolic acids with anti-inflammatory functions.Aim of the studyThe purpose of this research was to isolate phenolic acids from RSMA and investigate their anti-inflammatory effects and potential mechanisms.Materials and methodsNine already known compounds were obtained from RSMA. Their structures were elucidated through the spectroscopic analysis and comparing the reported data. The anti-inflammatory effects and potential mechanisms were investigated in LPS-stimulated THP-1 cells, using salvianolic acid B (SalB) as the positive control. The enzyme-linked immunosorbent assays (ELISA) were used to determine the secretory protein levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). And quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the mRNA levels of these inflammatory cytokines. The expression of TLR4, p65, p-p65, IκBα, and p-IκBα were measured using western blot.ResultsAll these compounds, except for rosmarinic acid (5) and isosalvianolic acid (6) for IL-6 protein levels, rosmarinic acid-o-β-D-glucopyranoside (3) for IL-6 mRNA, and rosmarinic acid-o-β-D-glucopyranoside (3), rosmarinic acid (5) and isosalvianolic acid (6) for TNF-α mRNA levels, remarkably inhibited the production of TNF-α, IL-1β, and IL-6 at the concentration of 5 and 25 μM in the mRNA and protein levels. Lithospermic acid (7) showed the strongest inhibitory effect among them and was similar to that of SalB. In particular, lithospermic acid (7) and SalB markedly downregulated the expressions of TLR4, p-p65, and p-IκBα induced by LPS in THP-1 macrophages.ConclusionsAll the phenolic acids displayed anti-inflammatory properties and the potential mechanisms involved the TLR4/NF-κB signal pathway. Results of this study indicate that phenolic acids may be effective constituents of RSMA to treat vascular diseases associated with inflammation.

Graphical abstract

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Paris in the spring: A review of the trade, conservation and opportunities in the shift from wild harvest to cultivation of Paris polyphylla (Trilliaceae)

Publication date: 10 August 2018
Source:Journal of Ethnopharmacology, Volume 222
Author(s): A.B. Cunningham, J.A. Brinckmann, Y.-F. Bi, S.-J. Pei, U. Schippmann, P. Luo
Ethnopharmacological relevanceP. polyphylla Smith is used in traditional medicine in China, India and Nepal and is likely to be similarly used through most of its geographic range. China is at the centre of demand for P. polyphylla where it is used as an ingredient in several very successful Chinese medicinal herbal formulations. The Chinese e-commerce platform 'alibaba.com', for example, lists 97 P. polyphylla items offered by 46 Asian suppliers, of which 21 are situated in the Chinese mainland, 12 in Nepal, 7 in India, 2 in Pakistan, and 1 each in Bhutan, Hong Kong, Thailand, and Vietnam. Products offered include the crude drug (dried whole or cut rhizomes), extracts and formulations containing this herbal drug.Aims of the reviewThe aims of this review were to assess the scale of the P. polyphylla trade, reviewing evidence on the impacts of wild harvest on P. polyphylla populations and on the role of cultivation as an alternative to wild harvest.Materials and methodsFirstly, we reviewed published information on Paris population biology and studies on impacts of wild P. polyphylla harvest from across the geographic range of this species. Secondly, global trade data for P. polyphylla were analysed. Thirdly, we reviewed published information on P. polyphylla cultivation and made field visits to P. polyphylla cultivation areas in Yunnan and Sichuan.ResultsSince the 1980s, there has been a 400-fold increase in the market price paid in China for P. polyphylla rhizomes, from 2.7 Chinese Yuan (CNY) per kg in the 1980s to market prices up to 1100 CNY per kg in 2017. Cross-border trade in dried P. polyphylla rhizomes occurs at three different scales. Firstly, an internal, national trade of P. polyphylla rhizomes within countries (such as India, Nepal and China). Secondly, trade in P. polyphylla rhizomes from Nepal (and possibly from Bhutan) to the two range states that have the largest traditional medicine trade in the world: China and India. Thirdly, trade in processed herbal products. In China, for example, P. polyphylla is widely used as an ingredient in several very successful herbal products, including a famous first aid treatment to stop bleeding. Some of these products are exported globally, in addition to entering into regional trade. Trade data in our review shows that c. 800–1050 t of P. polyphylla rhizomes are sold annually, significantly more than recorded in earlier studies. China is the only country where P. polyphylla is cultivated on a significant scale, although small-scale cultivation is taking place in India and Nepal.ConclusionsBased on the criteria for the inclusion of species in CITES Appendix II (Art. IV 2(a)), there is compelling evidence for adding Paris polyphylla. At the same time, cultivation of P. polyphylla outside of high conservation value habitats needs to be encouraged and supported. One way of doing this may be to develop separate, traceable supply chains for cultivated supplies in order to distinguish them from wild harvested stocks.

Graphical abstract

https://ift.tt/2IiRUBz