bluuebunny/crossref_metadata_2025 huggingface dataset:
EXPERT: Transfer Learning-enabled context-aware microbial source tracking
Authors: Chong Hui , Yu Qingyang , Zha Yuguo , Xiong Guangzhou , Wang Nan , Huang Xinhe , Huang Shijuan , Sun Chuqing , Wu Sicheng , Chen Wei-Hua , Coelho Luis Pedro , Ning Kang
Published: February 2021

Microbial source tracking quantifies the potential origin of microbial communities, facilitates better understanding of how the taxonomic structure and community functions were formed and maintained. However, previous methods involve a tradeoff between speed and accuracy, and have encountered difficulty in source tracking under many context-dependent settings. Here, we present EXPERT for context-aware microbial source tracking, in which we adopted a Transfer Learning approach to profoundly elevate and expand the applicability of source tracking, enabling biologically informed novel microbial knowledge discovery. We demonstrate that EXPERT can predict microbial sources with performance superior to other methods in efficiency and accuracy. More importantly, we demonstrate EXPERT’s context-aware ability on several applications, including tracking the progression of infant gut microbiome development and monitoring the changes of gut microbiome for colorectal cancer patients. Broadly, transfer learning enables accurate and context-aware microbial source tracking and has the potential for novel microbial knowledge discovery.
linc2function: A deep learning model to identify and assign function to long noncoding RNA (lncRNA)
Authors: Ramakrishnaiah Yashpal , Kuhlmann Levin , Tyagi Sonika
Published: February 2021

Motivation

LncRNAs are much more versatile and are involved in many regulatory roles inside the cell than previously believed. Existing databases lack consistencies in lncRNA annotations, and the functionality of over 95% of the known lncRNAs are yet to be established. LncRNA transcript identification involves discriminating them from their coding counterparts, which can be done with traditional experimental approaches, or viain silicomethods. The later approach employs various computational algorithms, including machine learning classifiers to predict the lncRNA forming potential of a given transcript. Such approaches provide an economical and faster alternative to the experimental methods. Currentin silicomethods mainly use primary-sequence based features to build predictive models limiting their accuracy and robustness. Moreover, many of these tools make use of reference genome based features, in consequence making them unsuitable for non-model species. Hence, there is a need to comprehensively evaluate the efficacy of different predictive features to build computational models. Additionally, effective models will have to provide maximum prediction performance using the least number of features in a species-agnostic manner.

It is popularly known in the protein world that “structure is function”. This also applies to lncRNAs as their functional mechanisms are similar to those of proteins. Generally, lncRNA function by structurally binding to its target proteins or nucleic acid forming complexes. The secondary structures of the lncRNAs are modular providing interaction sites for their interactome made of DNA, RNA, and proteins. Through these interactions, they epigenetically regulate cellular biology, thereby forming a layer of genomic programming on top of the coding genes. We demonstrate that in addition to using transcript sequence, we can provide comprehensive functional annotation by collating their interactome and secondary structure information.

Results

Here, we evaluated an exhaustive list of sequence-based, secondary-structure, interactome, and physicochemical features for their ability to predict the lncRNA potential of a transcript. Based on our analysis, we built different machine learning models using optimum feature-set. We found our model to be on par or exceeding the execution of the state-of-the-art methods with AUC values of over 0.9 for a diverse collection of species tested. Finally, we built a pipeline calledlinc2functionthat provides the information necessary to functionally annotate a lncRNA conveniently in a single window.

Availability

The source code is accessible use under MIT license in standalone mode, and as a webserver (https://bioinformaticslab.erc.monash.edu/linc2function).
Lateral electric field inhibits gel-to-fluid transition in lipid bilayers
Authors: Thomas Nidhin , Agrawal Ashutosh
Published: February 2021

We report evidence of lateral electric field-induced changes in the phase transition temperatures of lipid bilayers. Our atomic scale molecular dynamics simulations show that lateral electric field increases the melting temperature of DPPC, POPC and POPE bilayers. Remarkably, this shift in melting temperature is only induced by lateral electric field, and not normal electric field. This mechanism could provide new mechanistic insights into lipid-lipid and lipid-protein interactions in the presence of endogenous and exogenous electric fields.
Defensive freezing and its relation to approach-avoidance decision-making under threat
Authors: Klaassen Felix H. , Held Leslie , Figner Bernd , O’Reilly Jill X. , Klumpers Floris , de Voogd Lycia D. , Roelofs Karin
Published: February 2021

Successful responding to acutely threatening situations requires adequate approach-avoidance decisions. However, it is unclear how threat-induced states-like freezing-related bradycardia-impact the weighing of the potential outcomes of such value-based decisions. Insight into the underlying computations is essential, not only to improve our models of decision-making but also to improve interventions for maladaptive decisions, for instance in anxiety patients and first-responders who frequently have to make decisions under acute threat. Forty-two participants made passive and active approach-avoidance decisions under threat-of-shock when confronted with mixed outcome-prospects (i.e., varying money and shock amounts). Choice behavior was best predicted by a model including individual action-tendencies and bradycardia, beyond the subjective value of the outcome. Moreover, threat-related bradycardia interacted with subjective value, depending on the action-context (i.e., passive vs. active). Specifically, in action-contexts incongruent with participants’ intrinsic action-tendencies, strong freezers showed diminished effects of subjective value on choice. These findings illustrate the relevance of testing approach-avoidance decisions in relatively ecologically valid conditions of acute and primarily reinforced threat. These mechanistic insights into approach-avoidance conflict-resolution may inspire biofeedback-related techniques to optimize decision-making under threat. Critically, the findings demonstrate the relevance of incorporatinginternalpsychophysiological states andexternalaction-contexts into models of approach-avoidance decision-making.
Chemical defense and tonic immobility in early life stages of the Harlequin cabbage bug,Murgantia histrionica(Heteroptera: Pentatomidae)
Authors: Guerra-Grenier Eric , Liu Rui , Arnason John T. , Sherratt Thomas N.
Published: February 2021

Antipredation strategies are important for the survival and fitness of animals, especially in more vulnerable life stages. In insects, eggs and early juvenile stages are often either immobile or unable to rapidly flee and hide when facing predators. Understanding what alternative antipredation strategies they use, but also how those change over development time, is required to fully appreciate how species have adapted to biotic threats.Murgantia histrionicais a stink bug, conspicuously colored from egg to adult, known to sequester defensive glucosinolates from its cruciferous hosts as adults. We sought to assess whether this chemical defense is also present in its eggs and early nymphal instars and quantified how it fluctuates among life stages. In parallel, we looked at an alternative antipredation strategy, described for the first time in this species: tonic immobility. Our results show that the eggs are significantly more chemically defended than the first two mobile life stages, but not than the third instar. Tonic immobility is also favored by hatchlings, but less so by subsequent instars. We argue the case that over development time, tonic immobility is a useful defensive strategy until adequate chemical protection is achieved over an extended feeding period.
Gypenosides modulate NCX calcium flux, insulin secretion and cytoprotection in BRIN-BD11 pancreatic β-cells
Authors: Patibandla Chinmai , Shu Xinhua , Shaw Angus M , Dolan Sharron , Patterson Steven
Published: February 2021

Gypenosides are saponins extracted from the plantGynostemma pentaphyllum, suggested to have antidiabetic and anti-obesity potential. However, its mechanism of action is not fully understood. The present study aimed to investigate the cytoprotective and insulin stimulatory effects of gypenosides using the rat BRIN-BD11 β-cell line. Gypenosides provided a significant cytoprotective effect against palmitate-, peroxide- and cytokine-induced cytotoxicity, with upregulation of antioxidant genesNrf2,Cat,Sod1,andGpx1. Acutely, gypenosides enhanced intracellular calcium ([Ca2+]i) and insulin secretion in a dose-dependent manner. The presence of the sodium/calcium exchanger (NCX) reverse mode inhibitor SN-6 blocked the gypenosides mediated increase in [Ca2+]Ibut not the insulin secretion. These findings indicate that gypenosides may enhance [Ca2+]iby activating the reverse mode of NCX channels and a possible calcium-independent mechanism involved in their insulin secretion. Gypenosides also upregulate the antioxidant gene expression and protect against oxidative stress and lipotoxicity, providing the rationale for their observed antidiabetic actions.
Natural IgA andTNFRSF13Bpolymorphism: a double edged sword fueling balancing selection
Authors: Platt Jeffrey L. , de Mattos Barbosa Mayara Garcia , Huynh Daniel , Lefferts Adam R. , Katta Juhi , Kharas Cyra , Freddolino Peter , Bassis Christine M. , Wobus Christiane , Geha Raif , Bram Richard , Nunez Gabriel , Kamada Nobuhiko , Cascalho Marilia
Published: February 2021

TNFRSF13Bencodes the “transmembrane-activator and CAML-interactor” (TACI) receptor, which drives plasma cell differentiation. AlthoughTNFRSF13Bsupports host defense, dominant-negativeTNFRSF13Balleles are common in humans and other species and only rarely associate with disease. We reasoned the high frequency of disruptiveTNFRSF13Balleles reflects balancing selection, the loss of function conferring advantage in some settings. Testing that concept, we asked whether and how a common human dominant negative variant, TNFRSF13B A181E, imparts resistance to enteric pathogens. Mice engineered to express mono-allelic or bi-allelic A144E variants oftnrsf13B, corresponding to A181E exhibited striking resistance to pathogenicity and transmission ofC. rodentium, a murine pathogen that models enterohemorrhagicE. coli, and resistance was principally owed to deficiency of natural IgA in the intestine. In wild type mice with gut IgA and in mutant mice fed IgA, binding of Ig induces expression ofLEEencoded virulence genes, which confer pathogenicity and transmission. C. rodentiumand probably some other enteric organisms thus appropriated binding of otherwise protective antibodies to signal induction of the virulence program and the high prevalence ofTNFRSF13Bdominant negative variants thus reflects balancing selection.
Quantitative analysis and genome-scale modeling of human CD4+T-cell differentiation reveals subset-specific regulation of glycosphingolipid pathways
Authors: Sen Partho , Andrabi Syed Bilal Ahmad , Buchacher Tanja , Khan Mohd Moin , Ullah Ubaid , Lindeman Tuomas , Amaral Marina Alves , Hinkkanen Victoria , Kemppainen Esko , Dickens Alex M , Rasool Omid , Hyötyläinen Tuulia , Lahesmaa Riitta , Orešič Matej
Published: February 2021

T-cells are sentinels of adaptive cell-mediated immune responses. T-cell activation, proliferation and differentiation involves metabolic reprogramming involving the interplay of genes, proteins and metabolites. Here, we aim to understand the metabolic pathways involved in the activation and functional differentiation of human CD4+T-cell subsets (Th1, Th2, Th17 and iTregs). We combined genome-scale metabolic modeling, gene expression data, targeted and non-targeted lipidomics experiments, together within vitrogene knockdown experiments and showed that human CD4+T-cells undergo specific metabolic changes during activation and functional differentiation. In addition, we identified and confirmed the importance of ceramide and glycosphingolipid synthesis pathways in Th17 differentiation and effector functions. Finally, throughin vitrogene knockdown experiments, we substantiated the requirement of serine palmitoyl transferase (SPT), ade novosphingolipid pathway in the expression of proinflammatory cytokine (IL17A and IL17F) by Th17 cells. Our findings may provide a comprehensive resource for identifying CD4+T-cell-specific targets for their selective manipulation under disease conditions, particularly, diseases characterized by an imbalance of Treg / Th17 cells. Our data also suggest a role for elevated levels of ceramides in conditions comorbid with these diseases,e.g., obesity and insulin resistance.
Moving outside the lab: The viability of conducting sensorimotor learning studies online
Authors: Tsay Jonathan S. , Lee Alan S. , Ivry Richard B. , Avraham Guy
Published: February 2021

Collecting data online via crowdsourcing platforms has proven to be a very efficient way to recruit a large and diverse sample. Studies of motor learning, however, have been largely confined to the lab due to the need for special equipment to record movement kinematics and, as such, are typically only accessible to specific participants (e.g., college students). As a first foray to make motor learning studies accessible to a larger and more diverse audience, we developed an online, web-based platform (OnPoint) to collect kinematic data, serving as a template for researchers to create their own online sensorimotor control and learning experiments. As a proof-of-concept, we asked if fundamental motor learning phenomena discovered in the lab could be replicated online. In a series of three experiments, we observed a close correspondence between the results obtained online with those previously reported from research conducted in the laboratory. This web-based platform paired with online crowdsourcing can serve as a powerful new method for the study of motor control and learning.
In silicoassessment of missense point mutations on human cathelicidin LL-37
Authors: Porto William F. , Alencar Sergio A.
Published: February 2021

Cathelicidin antimicrobial peptides are a diverse family of cationic amphipathic peptides with multiple activities. In humans, cathelicidin LL-37 is one of the main host defense peptides with a remarkable medical and biotechnological potential. Deregulation of LL-37 expression has been associated with inflammatory diseases. However the effects of point mutations driven by single nucleotide polymorphisms (SNPs) on LL-37 are unknown. Here we applied an array of computational tools to investigate the effects of such mutations on LL-37 structure and activity. Due to the fact that, on cathelicidins, the prodomain is more conserved than the mature peptide, the SNP effect predictions were biased and, overall, resulted in neutral effects; and due to the slight changes in physicochemical properties, the antimicrobial predictions indicated the maintenance of such activity. Nonetheless, R07P, R07W, R29Q, R29W mutations reduced the peptide net charge, which in turn could result in less active LL-37 variants. Molecular dynamics data indicated that R07Q and N30Y mutations altered the LL-37 structure, leading to potential deleterious effects. In addition, the helix dipole is altered in G03A, R07P, R07W and L31P mutations, which could also alter the antimicrobial activity. Our results indicated that despite the mutations did not alter the residues from LL-37 active core, they could influence the antimicrobial activity and consequently, could be involved in inflammatory diseases.
An artificial self-assembling nanocompartment for organising metabolic pathways in yeast
Authors: Cheah Li Chen , Stark Terra , Adamson Lachlan S. R. , Abidin Rufika S. , Lau Yu Heng , Sainsbury Frank , Vickers Claudia E.
Published: February 2021

Metabolic pathways are commonly organised by sequestration into discrete cellular compartments. Compartments prevent unfavourable interactions with other pathways and provide local environments conducive to the activity of encapsulated enzymes. Such compartments are also useful synthetic biology tools for examining enzyme/pathway behaviour and for metabolic engineering. Here, we expand the intracellular compartmentalisation toolbox for budding yeast (Saccharomyces cerevisiae) with engineered Murine polyomavirus virus-like particles (MPyV VLPs). The MPyV system has two components: VP1 which self-assembles into the compartment shell; and a short anchor, VP2C, which mediates cargo protein encapsulation via binding to the inner surface of the VP1 shell. Destabilised GFP fused to VP2C was specifically sorted into VLPs and thereby protected from host-mediated degradation. In order to access metabolites of native and engineered yeast metabolism, VLP-based nanocompartments were directed to assemble in the cytosol by removal of the VP1 nuclear localisation signal. To demonstrate their ability to function as a metabolic compartment, MPyV VLPs were used to encapsulate myo-inositol oxygenase (MIOX), an unstable and rate-limiting enzyme in D-glucaric acid biosynthesis. Strains with encapsulated MIOX produced ~20% more D-glucaric acid compared to controls expressing ‘free’ MIOX - despite accumulating dramatically less expressed protein - and also grew to higher cell densities. These effects were linked to enzyme stabilisation and mitigation of cellular toxicity by the engineered compartment. This is the first demonstration in yeast of an artificial biocatalytic compartment that can participate in a metabolic pathway and establishes the MPyV platform as a promising synthetic biology tool for yeast engineering.
Vasoconstriction in isolated goat aorta does not increase mean aortic pressure
Authors: Gangadharan Naveen , Aravindhan V , Jebaraj Benjamin , Zachariah Shikha Mary , Devasahayam Suresh , Kumar G Saravana , Subramani Sathya
Published: February 2021

Vasoconstriction in small arteries and arterioles is known to increase resistance to flow, while vasoconstriction in large arteries and aorta is known to decrease their compliance. Besides this general understanding, there is no systematic documentation on what happens to small artery compliance and large artery resistance during vasoconstriction and the corresponding alterations in vascular pressure. The aim of the study is to assess the effect of adrenaline on goat aortae and small arteries in terms of resistance and compliance.

Isolated goat aortae and small arteries were perfused with a pulsatile pump and lumen pressure was recorded before and after addition of adrenaline. In the aortae, systolic pressure increased, diastolic pressure decreased, pulse pressure increased (p = 0.018, WSR); but the mean pressure remained the same (p = 0.357, WSR). Small artery vasoconstriction caused an increase in systolic, diastolic and mean pressures (p = 0.028, WSR). Using length, radius, and thickness data from the tissues and the tubes of the experimental set-up, electrical models were simulated to understand the biological data. The simulations allow us to infer that vasoconstriction in aorta leads to a reduction in compliance, but an increase in resistance if any, is not sufficient to change the mean aortic pressure. On the other hand, vasoconstriction in small arteries increases resistance, but a decrease in compliance if any, does not affect any of the four pressure parameters measured. Vasoconstriction in aorta decreases compliance and therefore increases pulse pressure but does not change resistance significantly enough to alter mean pressure.

Key Points Summary

The main aim of the study is to understand where exactly resistance (R) and compliance (C) components of the vasculature occur. There is no definitive evidence for the effect of large artery vasoconstriction on resistance and hence the mean arterial pressure.

The manuscript presents biological experiments studying the pressure response of goat aorta and small arteries to adrenaline (invitro) and the interpretations using equivalent electrical models.

The study shows that in aorta and large arteries, vasoconstriction does not lead to a reduction in lumen diameter sufficient to cause a rise in resistance and mean pressure as compared to small arteries.

Knowledge of exact location ofRandCin the arterial tree enables re-assessment of the differential action of vasoactive drugs on resistance versus compliance vessels once we resolve beat-to-beatRandCchanges in response to a drug. This way antihypertensive therapy can be tailored to address the specific cause of the type of hypertension.
The role of Gdf5 in the development of the zebrafish fin endoskeleton
Authors: Waldmann Laura , Leyhr Jake , Zhang Hanqing , Allalou Amin , Öhman-Mägi Caroline , Haitina Tatjana
Published: February 2021

Background

The development of the vertebrate limb skeleton requires a complex interaction of multiple factors to facilitate correct shaping and positioning of bones and joints. Growth and differentiation factor 5 (Gdf5), a member of the transforming growth factor-beta family (TGF-β) is involved in patterning appendicular skeletal elements including joints. Expression ofgdf5in zebrafish has been detected within the first pharyngeal arch jaw joint, fin mesenchyme condensations and segmentation zones in median fins, however little is known about the functional role of Gdf5 outside of Amniota.

Results

We generated CRISPR/Cas9 knockout ofgdf5in zebrafish and analysed the resulting phenotype at different developmental stages. Homozygousgdf5mutant zebrafish displayed changes in segmentation of the endoskeletal disc and, in consequence, loss of posterior radials in the pectoral fins. Mutant fish also displayed affected organisation and length of skeletal elements in the median fins, however joint formation and mineralisation process seemed unaffected.

Conclusions

Our study demonstrates the importance of Gdf5 for the paired and median fin endoskeleton development in zebrafish and reveals that the severity of the effect increases from anterior to posterior side of the elements. Our findings are consistent with phenotypes observed in human and mouse appendicular skeleton in response toGdf5knockout, suggesting a broadly conserved role for Gdf5 in Osteichthyes.
Cardiac progenitors auto-regulate second heart field cell fate via Wnt secretion
Authors: Miyamoto Matthew , Kannan Suraj , Uosaki Hideki , Kakani Tejasvi , Murphy Sean , Andersen Peter , Kwon Chulan
Published: February 2021

Proper heart formation requires coordinated development of two anatomically distinct groups of cells - the first and second heart fields (FHF and SHF). Given that congenital heart defects are often restricted to derivatives of the FHF or SHF, it is crucial to understand the mechanisms controlling their development. Wnt signaling has previously been implicated in SHF proliferation; however, the source of Wnts remains unknown. Through comparative gene analysis, we found upregulation of Wnts and Wnt receptor/target genes in the FHF and SHF, respectively, raising the possibility that early cardiac progenitors may secrete Wnts to influence SHF cell fate. To probe this further, we deletedWntless (Wls), a gene required for Wnt ligand secretion, in various populations of precardiac cells. Deletion of Wls in Mesp1+cells resulted in formation of a single chamber heart with left ventricle identity, implying compromised SHF development. This phenotype was recapitulated by deleting Wls in cells expressing Islet1, a pan-cardiac marker. Similarly, Wls deletion in cells expressing Nkx2.5, a later-expressed pan-cardiac marker, resulted in hypoplastic right ventricle, a structure derived from the SHF. However, no developmental defects were observed when deleting Wls in SHF progenitors. To gain mechanistic insights, we isolated Mesp1-lineage cells from developing embryos and performed single-cell RNA-sequencing. Our comprehensive single cell transcriptome analysis revealed that Wls deletion dysregulates developmental trajectories of both anterior and posterior SHF cells, marked by impaired proliferation and premature differentiation. Together, these results demonstrate a critical role of local precardiac mesodermal Wnts in SHF fate decision, providing fundamental insights into understanding heart field development and chamber formation.

Significance Statement

There is significant interest in understanding the mechanisms underlying heart formation to develop treatments and cures for patients suffering from congenital heart disease. In particular, we were interested in the intricacies of first (FHF) and second heart field (SHF) development, as many congenital heart defects present with heart field-specific etiologies. Here, we uncovered a novel relationship between specified cardiac progenitor cells and second heart field progenitors. Through genetic manipulation of Wnt secretion in developing mouse embryos, we identified a population of cardiac progenitor cells that acts as a local source of Wnts which are necessary for proper SHF development. Our single cell transcriptomic analysis of developing anterior mesoderm showed cardiac progenitor-secreted Wnts function through regulation of differentiation and proliferation among SHF progenitors. Thus, this study provides insight into the source and timing of Wnts required for SHF development, and points to the crucial role of co-developing cell populations in heart development.
Genomic and demographic processes differentially influence genetic variation across the X chromosome
Authors: Cotter Daniel J. , Webster Timothy H. , Wilson Melissa A.
Published: February 2021

Mutation, recombination, selection, and demography affect genetic variation across the genome. Increased mutation and recombination both lead to increases in genetic diversity in a region-specific manner, while complex demographic patterns shape patterns of diversity on a more global scale. The X chromosome is particularly interesting because it contains several distinct regions that are subject to different combinations and strengths of these processes, notably the pseudoautosomal regions (PARs) and the X-transposed region (XTR). The X chromosome thus can serve as a unique model for studying how genetic and demographic forces act in different contexts to shape patterns of observed variation. Here we investigate diversity, divergence, and linkage disequilibrium in each region of the X chromosome using genomic data from 26 human populations. We find that both diversity and substitution rate are consistently elevated in PAR1 and the XTR compared to the rest of the X chromosome. In contrast, linkage disequilibrium is lowest in PAR1 and highest on the non-recombining X chromosome, with the XTR falling in between, suggesting that the XTR (usually included in the non-recombining X) may need to be considered separately in future studies. We also observed strong population-specific effects on genetic diversity; not only does genetic variation differ on the X and autosomes among populations, but the effects of linked selection on the X relative to autosomes have been shaped by population-specific history. The substantial variation in patterns of variation across these regions provides insight into the unique evolutionary history contained within the X chromosome.

Significance Statement

Demography and selection affect the X chromosome differently from non-sex chromosomes. However, the X chromosome can be subdivided into multiple distinct regions that facilitate even more fine-scaled assessment of these processes. Here we study regions of the human X chromosome in 26 populations to find evidence that recombination may be mutagenic in humans and that the X-transposed region may undergo recombination. Further we observe that the effects of selection and demography act differently on the X chromosome relative to the autosomes across human populations. Together, our results highlight profound regional differences across the X chromosome, simultaneously making it an ideal system for exploring the action of evolutionary forces as well as necessitating its careful consideration and treatment in genomic analyses.
Structural and functional sex differences in the ventral pallidal vasopressin system are associated with the sex-specific regulation of juvenile social play behavior in rats
Authors: Lee J.D.A. , Reppucci C.J. , Bowden S.M. , Huez E.D.M. , Bredewold R. , Veenema A.H.
Published: February 2021

The ventral pallidum (VP) has been implicated in the regulation of rewarding adult social behaviors, such as pair-bonding and sociosexual motivation. However, the role of the VP in regulating rewarding juvenile social behaviors, such as social play, is unknown. Social play is predominantly displayed by juveniles of many mammalian species and engagement in social play helps develop social competence. In this study, we determined whether the VP is involved in regulating social play in juvenile rats by temporarily inactivating the VP via bilateral infusions of muscimol, the GABAAreceptor agonist. Muscimol treatment decreased social play duration in males and females compared to the same-sex control groups. We then focused on the vasopressin (AVP) system in the VP as one potential modulator of social play. We examined the organization of the AVP system in the VP in juvenile rats and found robust sex differences, with denser AVP-immunoreacive fibers and denser vasopressin 1a receptor (V1aR) binding in males compared to females, but a greater number of V1aR-expressing cells in females compared to males. Next, we determined whether exposure to social play changed the activation of V1aR-expressing VP cells in male and female juvenile rats. We found that exposure to social play enhanced the number of V1aR-expressing VP cells co-expressingfos, a marker of neuronal activation, in males only. Finally, we determined the causal involvement of AVP signaling in the VP in social play behavior by infusion of a specific V1aR antagonist into the VP prior to social play exposure. We found that V1aR blockade in the VP increased social play duration in juvenile male rats but decreased social play duration in juvenile female rats compared to same-sex control groups. These findings reveal structural and functional sex differences in the AVP system in the VP that are associated with the sex-specific regulation of juvenile social play behavior.
Cell of all trades: oligodendrocyte precursor cells in synaptic, vascular, and immune function
Authors: Akay Leyla Anne , Effenberger Audrey H. , Tsai Li-Huei
Published: February 2021

Oligodendrocyte precursor cells (OPCs) are not merely a transitory progenitor cell type, but rather a distinct and heterogeneous population of glia with various functions in the developing and adult central nervous system. In this review, we discuss the fate and function of OPCs in the brain beyond their contribution to myelination. OPCs are electrically sensitive, form synapses with neurons, support blood–brain barrier integrity, and mediate neuroinflammation. We explore how sex and age may influence OPC activity, and we review how OPC dysfunction may play a primary role in numerous neurological and neuropsychiatric diseases. Finally, we highlight areas of future research.
Dietary interventions as regulators of stem cell behavior in homeostasis and disease
Authors: Novak Jesse S.S. , Baksh Sanjeethan C. , Fuchs Elaine
Published: February 2021

Stem cells maintain tissues by balancing self-renewal with differentiation. A stem cell's local microenvironment, or niche, informs stem cell behavior and receives inputs at multiple levels. Increasingly, it is becoming clear that the overall metabolic status of an organism or metabolites themselves can function as integral members of the niche to alter stem cell fate. Macroscopic dietary interventions such as caloric restriction, the ketogenic diet, and a high-fat diet systemically alter an organism's metabolic state in different ways. Intriguingly, however, they all converge on a propensity to enhance self-renewal. Here, we highlight our current knowledge on how dietary changes feed into stem cell behavior across a wide variety of tissues and illuminate possible explanations for why diverse interventions can result in similar stem cell phenotypes. In so doing, we hope to inspire new avenues of inquiry into the importance of metabolism in stem cell homeostasis and disease.
Learning from the worm: the effectiveness of protein-bound Moco to treat Moco deficiency
Authors: Sewell Aileen K. , Han Min
Published: February 2021

Molybdenum cofactor (Moco) is synthesized endogenously in humans and is essential for human development. Supplementation of Moco or its precursors has been explored as a therapy to treat Moco-deficient patients but with significant limitations. By using the nematode C. elegans as a model, Warnhoff and colleagues (pp. 212–217) describe the beneficial impact of protein-bound Moco supplementation to treat Moco deficiency. If such an effect is conserved, this advance from basic research in worms may have significant clinical implications as a novel therapy for molybdenum cofactor deficiency.
Wild and domestic savanna herbivores increase smaller vertebrate diversity, but less than additively
Authors: Wells Harry B. M. , Kimuyu Duncan M. , Odadi Wilfred O. , Dougill Andrew J. , Stringer Lindsay C. , Young Truman P.
Published: February 2021

Cattle and other livestock graze more than a quarter of the world's terrestrial area and are widely regarded to be drivers of global biodiversity declines. Studies often compare the effects of livestock presence/absence but, to our knowledge, no studies have tested for interactive effects between large wild herbivores and livestock at varying stocking rates on small‐bodied wild vertebrates.

We investigated the effects of cattle stocking rates (none/moderate/high) on the diversity of wildlife 0.05–1,000 kg using camera traps at a long‐term exclosure experiment within a semi‐arid savanna ecosystem in central Kenya. In addition, by selectively excluding wild ‘mesoherbivores’ (50–1,000 kg) and ‘megaherbivores’ (>1,000 kg; elephant and giraffe), we tested whether the presence of these two wild herbivore guilds (collectively, ‘larger wild herbivores’) mediates the effect of cattle stocking rate on habitat use and diversity of ‘smaller wildlife’ (mammals ranging between 10 and 70 cm shoulder height and birds).

Our results show that cattle enhance alpha diversity of smaller wildlife (with or without larger wild herbivore presence) and of all wildlife 0.05–1,000 kg (with or without megaherbivore presence), by altering vegetation structure. However, for smaller wildlife, this effect is less pronounced in the presence of larger wild herbivores, which also shorten grass. In the absence of cattle, mesoherbivore‐accessible sites showed higher alpha diversity of smaller wildlife than sites excluding mesoherbivores.

Smaller wildlife habitat use was increased by high cattle stocking rates and wild mesoherbivores more in the presence of the other.

Synthesis and applications. Our findings imply that grazing, whether by livestock or wildlife, can enhance local savanna wildlife diversity. The biodiversity benefits of localised increases in herbivory are likely to be due to shortened grass and associated visibility improvements (for predator avoidance/foraging). This suggests that land managers can increase local biodiversity by shortening grass, with wild or domestic herbivores (or both), at least in patches within a taller grass matrix.
‘It's the best job in the world, but one of the hardest, loneliest, most misunderstood roles in a school.’ Understanding the complexity of the SENCO role post‐SEND reform
Authors: Curran Helen , Boddison Adam
Published: February 2021

In schools, the Special Educational Needs Coordinator (SENCO) could be considered a key policy implementer of special educational needs and inclusive policy. Issues related to time, status and the effective facilitation of the SENCO role have been reported on extensively, yet literature has predominantly focused on the role prior to the introduction of the Special Educational Needs and Disability (SEND) reforms in 2014.

This paper reports on research which explored the SENCO role post‐reform. The research aimed to understand how widely the role varied across differing educational settings and phases, whilst also exploring the breadth and depth of the role, post‐SEND reform. The research design was mixed methods and had two phases: online focus groups (n = 15), followed by a national online survey (n = 1903).

The findings suggest that the facilitation of the SENCO role remains problematic post‐reform. Constraints include the time to undertake responsibilities, the increasing breadth of the role and how the role is understood by others. This combined with increased external bureaucracy, budgetary constraints and a lack of consistency nationally has led to a situation where only approximately one‐third of SENCOs intend to remain in the role in five years’ time.
Changing the attitudes of high school students towards intellectual disabilities: the contribution of a social coexistence programme
Authors: Vasileiadis Ilias , Koutras Spyros , Stagiopoulos Petros
Published: February 2021

Students’ attitudes towards peers with intellectual disabilities are mostly negative, and negative attitudes appear more among secondary education students than any other age group. Social coexistence programmes are intervention programmes implemented by school psychologists to manage and change negative attitudes and enforce social interaction with students with disabilities. The research sample consisted of 193 public high school students in Greece who were given the Chedoke–McMaster Attitudes Toward Children with Handicaps (CATCH) Scale. The study aimed to explore whether there is a change in the attitudes of high school students towards peers with intellectual disabilities after participation in a social coexistence programme. The findings showed that students who participated in the programme had more positive attitudes towards people with intellectual disabilities after the completion of the programme. The above findings confirm the research on the possibility of changing attitudes of secondary school students towards peers with disabilities and reinforce the need for the systematic development of social coexistence programmes for the entire student population. Future research should focus on the benefits of students with disabilities from their participation in social coexistence programmes.
The Value of USDA Announcements in the Electronically Traded Corn Futures Market: A Modified Sufficient Test with Risk Adjustments
Authors: Huang Joshua , Serra Teresa , Garcia Philip
Published: February 2021

The paper assesses the value of USDA information in the electronic corn futures markets. While recent research has documented large price volatility spikes after USDA announcements, increased volatility does not directly translate into value. Using multiple newly developed risk‐premium measures and intraday data, we extend the Carter and Galopin approach based on estimating the risk‐adjusted profits that accrue to advanced USDA information. Using the 2010–2020 period, the analysis demonstrates that USDA announcement surprises have economic value, with WASDE surprises from NASS‐WASDE joint events being always valuable under all risk preferences. While the value is sensitive to these preferences, risk is relatively small because prices usually move in the direction of the market surprise which minimises losses. NASS surprises also contain value, though less than WASDE and only for the less risk averse traders. While overall risk is generally small, the intensified volatility right after the announcement points to the presence of noise and to the inadequacy of inferring the value of public information through price variability alone.
Milk proteins and their derived peptides on bone health: Biological functions, mechanisms, and prospects
Authors: Bu Tingting , Zheng Jiexia , Liu Ling , Li Shanshan , Wu Jianping
Published: February 2021

Bone is a dynamic organ under constant metabolism (or remodeling), where a delicate balance between bone resorption and bone formation is maintained. Disruption of this coordinated bone remodeling results in bone diseases, such as osteoporosis, the most common bone disorder characterized by decreased bone mineral density and microarchitectural deterioration. Epidemiological and clinical evidence support that consumption of dairy products is beneficial for bone health; this benefit is often attributed to the presence of calcium, the physiological contributions of milk proteins on bone metabolism, however, are underestimated. Emerging evidence highlighted that not only milk proteins (including individual milk proteins) but also their derived peptides positively regulate bone remodeling and attenuate bone loss, via the regulation of cellular markers and signaling of osteoblasts and osteoclasts. This article aims to review current knowledge about the roles of milk proteins, with an emphasis on individual milk proteins, bioactive peptides derived from milk proteins, and effect of milk processing in particular fermentation, on bone metabolism, to highlight the potential uses of milk proteins in the prevention and treatment of osteoporosis, and, to discuss the knowledge gap and to recommend future research directions.
Investigating the prevalence of intimate partner violence victimisation in women presenting to the emergency department in suicidal crisis
Authors: Rasmussen Victoria , Steel Zachary , Spangaro Jo , Torok Michelle
Published: February 2021

Objective

To investigate the prevalence of intimate partner violence (IPV) and frequency of victimisation questioning by hospital staff in women presenting to EDs for suicide‐related complaints and injuries.

Methods

A cross‐sectional survey design was used to assess IPV and ED experiences among women with a recent (<18 months) suicide‐related presentation to EDs within six Local Health Districts across New South Wales. Women aged 16 years and over, residing in participating health districts were recruited in‐person by hospital staff, or via Facebook advertisements. Variables assessed included demographic characteristics, psychosocial assessment coverage and exposure to IPV (Composite Abuse Scale [Revised]‐Short‐Form). Binary logistic regression was used to test for independent associations between variables on victimisation questioning by hospital staff.

Results

A total of 563 women completed questionnaires following presentation to the ED for a suicide attempt (n = 329; 58%) or suicide crisis (n = 234; 42%). Of these, 200 women (36%) reported IPV exposure in the 18 months prior and 141 women (25%) reported earlier lifetime victimisation. Of the 341 women with a history of IPV, 155 women (45%) were asked about victimisation by hospital staff. Younger age and lower socio‐economic status were significantly associated with questioning (P = 0.03).

Conclusion

Findings suggest a large proportion of women seeking support for suicide in the ED are affected by IPV, although few are asked about abuse experiences. Victimisation is associated with complex health issues and heightened mortality risk, which carry important implications for patient‐care. Findings support routine ED screening and can be applied to stratify risk within IPV responses.
Dysphagia management in Parkinson's disease: Comparison of the effect of thickening agents on taste, aroma, and texture
Authors: Baert Florence , Vlaemynck Geertrui , Beeckman Anne‐Sophie , Van Weyenberg Stephanie , Matthys Christophe
Published: February 2021

Dysphagia is a frequent symptom in Parkinson's disease (PD). Thickening liquids facilitates safe swallowing, however, low treatment compliance is a major issue, due to patients’ dislike of thickened liquids. Some studies suggest a negative impact of gum‐based thickeners, currently most used in clinical practice, on sensory properties compared to starch‐based thickeners. This has not yet been investigated in PD. This study's aim was to compare taste, texture, and aroma of gum‐based and starch‐based thickened soups in participants with PD. Gum‐based resource thicken up clear (RTUC) and starch‐based kitchen products potato starch (PS) and quinoa flour (QF) were evaluated in broccoli soup. Texture, aroma, and taste were characterized by rheology, volatile, and sensory profiling. Thickened soups were evaluated in participants with PD and controls through a paired comparison test. Reduced release of 61.4%, 46.2%, and 38.5% of volatiles was observed after thickening with RTUC, PS, and QF, respectively. Overall taste intensity was reduced in RTUC‐ and PS‐thickened soup, respectively. Taste and aroma of PS‐thickened soup were considered more intense by 70.3% and 63.8% of all participants, respectively (n = 36 PD, n = 41 controls), 56.3% preferred the PS‐thickened soup's texture . Taste and aroma of QF‐thickened soup were considered more intense by 68.1% and 65.6% of all participants, respectively (n = 47 PD, n = 31 controls), 58.0% preferred the QF‐thickened soup's texture. Starch‐based thickeners demonstrated higher taste and aroma intensity. However, volatile and sensory profiling demonstrated reduced taste and aroma in all thickeners. Combining kitchen products with flavor enhancers may increase palatability of thickened beverages.
Effectiveness of EGFR‐TKI rechallenge immediately after PD‐1 blockade failure
Authors: Kaira Kyoichi , Kobayashi Kunihiko , Shiono Ayako , Yamaguchi Ou , Hashimoto Kosuke , Mouri Atsuto , Shinomiya Shun , Miura Yu , Imai Hisao , Kagamu Hiroshi
Published: February 2021

Background

There is currently insufficient information available on effective therapies that can be administered to patients with non‐small cell cancer (NSCLC) who develop resistance to epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs). However, sequential treatment via programmed death‐1 (PD‐1) blockade followed by EGFR‐TKI rechallenge is suggested to improve the therapeutic efficacy in such patients.

Methods

A total of 75 patients with advanced NSCLC harboring sensitive EGFR mutations treated with afatinib, erlotinib, or gefitinib after EGFR‐TKI treatment failure were retrospectively analyzed. Among them, 13 patients were treated with EGFR‐TKI rechallenge immediately after the failure of PD‐1 blockade therapy (experimental group) and the remaining 62 patients did not receive PD‐1 inhibitor therapy before EGFR‐TKI rechallenge (control group). Blood samples were collected at two time points; before the initiation of anti‐PD‐1 therapy and at EGFR‐TKI rechallenge.

Results

The objective response rates of EGFR‐TKI rechallenge in the experimental and control groups were 46.1% and 16.1%, respectively, with a significant difference (p = 0.026). In the experimental group, the median progression‐free survival (PFS) and overall survival (OS) after EGFR‐TKI rechallenge were 5.0 and 25.0 months, respectively, and no statistically significant difference in the percentage of lymphocytes before immune checkpoint inhibitor (ICI) therapy and EGFR‐TKIs was observed in patients with partial response (PR) and without PR after EGFR‐TKI rechallenge. In particular, the sequential treatment of PD‐1 blockade therapy followed by EGFR‐TKI rechallenge was consecutively repeated three times in two out of 13 patients in the experimental group, and EGFR‐TKI rechallenge consecutively for the third time yielded a PR without increased toxicities.

Conclusions

EGFR‐TKI rechallenge immediately after PD‐1 blockade treatment was identified as an effective therapy for NSCLC patients with resistance to EGFR‐TKIs.