bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined Effects of Standing and Passive Heating on Attenuating Sitting-Induced Vascular Dysfunction
Authors: Caldwell Aaron R. , Jansen Lisa T. , Rosa-Caldwell Megan E. , Howie Erin K. , Gallagher Kaitlin M. , Turner Ronna C. , Ganio Matthew S. 
Published: May 2020

AbstractRecent evidence suggests prolonged sitting strains the arteries through angulations that create turbulent blood flow. This turbulent flow reduces flow-mediated dilation (FMD), a key indicator of vascular health. The purpose of this study was to determine if arterial angulations (through sitting or standing), shear stress (through local heating), or a combination of these factors affected vascular function. In addition, we sought examined the impact of biological sex on these responses.MethodsTwenty-six healthy, young (18-40 years old) males (n=13) and females (n=13) participated. Participants completed two experimental trials (2-h sitting and 2-h standing), and, in a randomized fashion, one leg was passively heated. Flow-mediated dilation (FMD) at the superficial femoral artery (SFA), and central and peripheral pulse-wave velocity (PWV) were measured using vascular ultrasound.ResultsThere was a non-significant decrease in FMD (- 1.48%;p =.06) during sitting and the decline in FMD was not different between biological sexes (−1.96% vs -0.93%;p =.49, males and females respectively). Passive heating (1.42%;p< .05) and standing (1.42%;p< .05) both improved FMD in comparison to sitting. However, standing resulted in a significant increase in peripheral PWV (50 cm/s;p< .05). Interestingly, the standing was not well tolerated among female participants with seven participants having to stop their initial trial early due to lightheadedness.ConclusionsBoth interventions appear to be equally effective at mitigating reductions FMD associated with sitting, but standing increased peripheral PWV. In addition, it does not appear that biological sex moderates these physiological responses.New FindingsWhat is the central question of this study?Prolonged sitting can cause acutely vascular dysfunction while interventions such as local heating or standing have been explored they have not been used in combination and the role of biological sex has not been fully explored.What is the main finding and its importance?In this study we demonstrate that either local heating or standing are effective at reducing some of the vascular dysfunction associated with prolonged sitting. Biological sex did not appear appear to play a role in this response. However, standing may also cause some negative effects such as increased arterial stiffness and increase the risk of syncope.
Locating the sex determining region of linkage group 12 of guppy (Poecilia reticulata)
Authors: Charlesworth Deborah , Bergero Roberta , Graham Chay , Gardner Jim , Yong Lengxob 
Published: May 2020

AbstractWe describe new genetic mapping results from 6 full-sib families in the guppy (Poecilia reticulata), two of which included recombinants between the X and Y chromosomes. These recombinants confirm that the guppy sex-determining locus is in the region identified by all previous studies, including a recent report suggesting a candidate sex-determining gene in this fish, close to the pseudo-autosomal region (or PAR) at the chromosome terminus. Our results suggest the presence of some errors in the current assembly of the guppy genome. In males, crossing over occurs at a very high rate in the PAR, and our genetic map of the region allows us to correct the marker order. We also identified two unplaced scaffolds carrying genes that map to the PAR. Genetic mapping cannot be used to order markers in the region where crossing over is infrequent. However, our recombinant male is informative about the order, under the reasonable assumption that crossovers are infrequent. Our mapping families and natural population samples also show that the recently proposed candidate for this species’ sex-determining gene is not completely sex-linked. We detect an association between individuals’ sex and an SNP in the sex-determining region, but not with a marker 0.9 Mb away from it, suggesting that variants in this region may be in linkage disequilibrium with the actual sex-determining factor, but that the factor itself has not yet been identified. So far, no consistently male-specific variant has been identified in the guppy sex-determining region.
Comparing proportional and ordinal dominance ranks reveals multiple competitive landscapes in an animal society
Authors: Levy Emily J , Zipple Matthew N , McLean Emily , Campos Fernando A , Dasari Mauna , Fogel Arielle S , Franz Mathias , Gesquiere Laurence R , Gordon Jacob B , Grieneisen Laura , Habig Bobby , Jansen David J , Learn Niki H , Weibel Chelsea J , Altmann Jeanne , Alberts Susan C , Archie Elizabeth A 
Published: May 2020

AbstractAcross group-living animals, linear dominance hierarchies lead to disparities in access to resources, health outcomes, and reproductive performance. Studies of how dominance rank affects these outcomes typically employ one of several dominance rank metrics without examining the assumptions each metric makes about its underlying competitive processes. Here we compare the ability of two dominance rank metrics—ordinal rank and proportional or ‘standardized’ rank—to predict 20 distinct traits in a well-studied wild baboon population in Amboseli, Kenya. We propose that ordinal rank best predicts outcomes when competition is density-dependent, while proportional rank best predicts outcomes when competition is density-independent. We found that for 75% (15/20) of the traits, one of the two rank metrics performed better than the other. Strikingly, all male traits were better predicted by ordinal than by proportional rank, while female traits were evenly split between being better predicted by proportional or ordinal rank. Hence, male and female traits are shaped by different competitive regimes: males’ competitive environments are largely driven by density-dependent resource access (e.g., access to estrus females), while females’ competitive environments are shaped by both density-independent resource access (e.g. distributed food resources) and density-dependent resource access. However, traits related to competition for social and mating partners are an exception to this sex-biased pattern: these traits were better predicted by ordinal rank than by proportional rank for both sexes. We argue that this method of comparing how different rank metrics predict traits of interest can be used as a way to distinguish between different competitive processes operating in animal societies.
Neonatal immune challenge induces female-specific changes in social behavior and somatostatin cell number, independent of microglial inflammatory signaling
Authors: Smith Caroline J. , Kingsbury Marcy A. , Dziabis Julia E. , Hanamsagar Richa , Malacon Karen E. , Tran Jessica N. , Norris Haley A. , Gulino Mary , Bilbo Staci D. 
Published: May 2020

AbstractDecreases in social behavior are a hallmark aspect of acute “sickness behavior” in response to infection. However, immune insults that occur during the perinatal period may have long-lasting consequences for adult social behavior by impacting the developmental organization of underlying neural circuits. Microglia, the resident immune cells of the central nervous system, are sensitive to immune stimulation and play a critical role in the developmental sculpting of neural circuits, making them likely mediators of this process. Here, we investigated the impact of a postnatal day (PND) 4 lipopolysaccharide (LPS) challenge on social behavior in adult mice. Somewhat surprisingly, neonatal LPS treatment decreased sociability in adult female, but not male mice. LPS-treated females also displayed reduced social interaction and social memory in a social discrimination task as compared to saline-treated females. Somatostatin (SST) interneurons within the anterior cingulate cortex (ACC) have recently been suggested to modulate a variety of social behaviors. Interestingly, the female-specific changes in social behavior observed here were accompanied by an increase in SST interneuron number in the ACC. Finally, these changes in social behavior and SST cell number do not appear to depend on microglial inflammatory signaling, because microglia-specific genetic knock-down of myeloid differentiation response protein 88 (MyD88; the removal of which prevents LPS from increasing proinflammatory cytokines such as TNFα and IL-1β) did not prevent these LPS-induced changes. This study provides novel evidence for enduring effects of neonatal immune activation on social behavior and SST interneurons in females, independent of microglial inflammatory signaling.
Modeling and Analyzing Neural Signals with Phase Variability using the Fisher-Rao Registration
Authors: Zhao Weilong , Xu Zishen , Li Wen , Wu Wei 
Published: May 2020

AbstractThe Dynamic Time Warping (DTW) has recently been introduced to analyze neural signals such as EEG and fMRI where phase variability plays an important role in the data. In this study, we propose to adopt a more powerful method, referred to as the Fisher-Rao Registration (FRR), to study the phase variability. We systematically compare the FRR with the DTW in three aspects: 1) basic framework, 2) mathematical properties, and 3) computational efficiency. We show that the FRR has superior performance in all these aspects and the advantages are well illustrated with simulation examples. We then apply the FRR method to two real experimental recordings – one fMRI and one EEG data set. It is found the FRR method properly removes the phase variability in each set. Finally, we use the FRR framework to examine brain networks in these two data sets and the result demonstrates the effectiveness of the new method.
Macrophages inhibit and enhance endometriosis depending on their origin
Authors: Hogg Chloe , Dhami Priya , Rosser Matthew , Mack Matthias , Soong Daniel , Pollard Jeffrey W , Jenkins Stephen J , Horne Andrew W , Greaves Erin 
Published: May 2020

AbstractMacrophages are intimately involved in the pathophysiology of endometriosis, a chronic inflammatory disorder characterized by the growth of endometrial-like tissue (lesions) outside the uterus. By combining genetic and pharmacological monocyte and macrophage depletion strategies we determined the ontogeny and function of macrophages in a mouse model of induced endometriosis. We demonstrate that lesion-resident macrophages are derived from eutopic endometrial tissue, infiltrating large peritoneal macrophages (LpM) and monocytes. Furthermore, we found endometriosis to trigger continuous recruitment of monocytes and expansion of CCR2+ LpM. Depletion of eutopic endometrial macrophages results in smaller endometriosis lesions, whereas constitutive inhibition of monocyte recruitment significantly reduces peritoneal macrophage populations and increased the number of lesions. We propose a putative model whereby endometrial macrophages are pro-endometriosis whilst newly-recruited monocyte-derived macrophages, possibly in LpM form, are ‘anti-endometriosis’. These observations highlight the importance of monocyte-derived macrophages in limiting disease progression.
Transcriptional profiling reveals a subset of human breast tumors that retain wtTP53but display mutant p53-associated features
Authors: Benor Gal , Fuks Garold , Chin Suet-Feung , Rueda Oscar , Mukherjee Saptaparna , Arandkar Sharathchandra , Aylon Yael , Caldas Carlos , Domany Eytan , Oren Moshe 
Published: May 2020

AbstractTP53gene mutations are very common in human cancer. While such mutations abrogate the tumor suppressive activities of the wild type (wt) p53 protein, some of them also endow the mutant protein with oncogenic gain-of-function (GOF), facilitating cancer progression. Yet, p53 may acquire altered functionality even without being mutated; in particular, experiments with cultured cells revealed that wt p53 can be rewired to adopt mutant-like features in response to growth factors or cancer-mimicking genetic manipulations. To assess whether such rewiring also occurs in human tumors, we interrogated gene expression profiles and pathway deregulation patterns in the METABRIC breast cancer (BC) dataset as a function ofTP53gene mutation status. Harnessing the power of machine learning, we optimized a gene expression classifier for ER+Her2- patients that distinguishes tumors carryingTP53mutations from those retaining wtTP53. Interestingly, a small subset of wtTP53tumors displayed gene expression and pathway deregulation patterns markedly similar to those ofTP53-mutated tumors. Moreover, similar toTP53mutated tumors, these “pseudomutant” cases displayed a signature for enhanced proliferation and had worse prognosis than typical wt p53 tumors. Notably, these tumors revealed upregulation of genes which, in BC cell lines, were reported to be positively regulated by p53 GOF mutants. Thus, such tumors may benefit from mutant p53-associated activities without having to accrueTP53mutations.
Manipulation of the human tRNA pool reveals distinct tRNA sets that act in cellular proliferation or cell cycle arrest
Authors: Aharon-Hefetz Noa , Frumkin Idan , Mayshar Yoav , Dahan Orna , Pilpel Yitzhak , Rak Roni 
Published: May 2020

AbstractDifferent subsets of the tRNA pool in human are expressed in different cellular conditions. The “proliferation-tRNAs” are induced upon normal and cancerous cell division, while the “differentiation tRNAs” are active in non-dividing, differentiated cells. Here we examine the essentiality of the various tRNAs upon cellular growth and arrest. We established a CRISPR-based editing procedure with sgRNAs that each target a tRNA family. We measured tRNA essentiality for cellular growth and found that most proliferation tRNAs are essential compared to differentiation tRNAs in rapidly growing cell lines. Yet in more slowly dividing lines, the differentiation tRNAs were more essential. In addition, we measured these tRNAs roles upon response to cell cycle arresting signals. Here we detected a more complex behavior with both proliferation-tRNAs and differentiation tRNAs showing various levels of essentiality. These results provide the so-far most comprehensive functional characterization of human tRNAs with intricate roles in various proliferation states.
Post-transcriptional regulation of cellulose synthase genes by small RNAs derived from CESA antisense transcripts
Authors: Nething Daniel B. , Mishler-Elmore John W. , Held Michael A. 
Published: May 2020

AbstractTranscriptional regulatory mechanisms governing plant cell wall biosynthesis are incomplete. Expression programs that activate wall biosynthesis are well understood, but mechanisms that control the attenuation of gene expression networks remain elusive. Previous work has shown that small RNAs (sRNAs) derived from theHvCESA6 (Hordeum vulgare, Hv) antisense transcripts are naturally produced and are capable of regulating aspects of wall biosynthesis. Here, we further test the hypothesis thatCESA-derived sRNAs generated fromCESAantisense transcripts are involved in the regulation of cellulose and broader cell wall biosynthesis. Antisense transcripts were detected for some, but not all members of theCESAgene family in both barley andBrachypodium distachyon. Phylogenetic analysis indicates that antisense transcripts are detected for most primary cell wall CESA genes, suggesting a possible role in the transition from primary to secondary cell wall biosynthesis. Focusing on one antisense transcript,HvCESA1shows dynamic expression throughout development, is correlated with corresponding sRNAs over the same period and is anticorrelated withHvCESA1mRNA expression. To assess the broader impacts ofCESA-derived sRNAs on the regulation of cell wall biosynthesis, transcript profiling was performed on barley tissues overexpressingCESA-derived sRNAs. Together the data support the hypothesis thatCESAantisense transcripts function, through an RNA-induced silencing mechanism, to degradecistranscripts, and may also triggertrans-acting silencing on related genes to alter the expression of cell wall gene networks.
A Novel Efficient L-Lysine Exporter Identified by Functional Metagenomics
Authors: Malla Sailesh , van der Helm Eric , Darbani Behrooz , Wieschalka Stefan , Forster Jochen , Borodina Irina , Sommer Morten O. A. 
Published: May 2020

AbstractLack of active export system often limits the industrial bio-based production processes accumulating the intracellular product and hence complexing the purification steps. L-lysine, an essential amino acid, is produced biologically in quantities exceeding two million tons per year; yet, L-lysine production is challenged by efficient export system at high titres during fermentation. To address this issue, new exporter candidates for efficient efflux of L-lysine are needed. Using metagenomic functional selection, we identified 58 genes encoded on 28 unique metagenomic fragments from cow gut microbiome library that improved L-lysine tolerance. These genes include a novel putative L-lysine transporter, belonging to a previously uncharacterized EamA superfamily. Characterization usingXenopus oocyteexpression system as well as anEscherichia colihost demonstrates activity as a L-lysine transporter. This novel exporter improved L-lysine tolerance inE. coliby 40% and enhanced the specific productivity of L-lysine in an industrialCorynebacterium glutamicumstrain by 12%. Our approach allows the sequence-independent discovery of novel exporters and can be deployed to increase titres and productivity of toxicity-limited bioprocesses.
Protoporphyrin IX and verteporfin prevent SARS-CoV-2 infectionin vitroand in a mouse model expressing human ACE2
Authors: Gu Chenjian , Wu Yang , Guo Huimin , Zhu Yuanfei , Xu Wei , Wang Yuyan , Zhou Yu , Sun Zhiping , Cai Xia , Li Yutang , Liu Jing , Huang Zhong , Yuan Zhenghong , Zhang Rong , Deng Qiang , Qu Di , Xie Youhua 
Published: May 2020

AbstractThe SARS-CoV-2 infection is spreading rapidly worldwide. Efficacious antiviral therapeutics against SARS-CoV-2 is urgently needed. Here, we discovered that protoporphyrin IX (PpIX) and verteporfin, two FDA-approved drugs, completely inhibited the cytopathic effect produced by SARS-CoV-2 infection at 1.25 μM and 0.31 μM respectively, and their EC50 values of reduction of viral RNA were at nanomolar concentrations. The selectivity indices of PpIX and verteporfin were 952.74 and 368.93, respectively, suggesting broad margin of safety. Importantly, PpIX and verteporfin prevented SARS-CoV-2 infection in mice adenovirally transduced with human ACE2. The compounds, sharing a porphyrin ring structure, were shown to bind viral receptor ACE2 and interfere with the interaction between ACE2 and the receptor-binding domain of viral S protein. Our study suggests that PpIX and verteporfin are potent antiviral agents against SARS-CoV-2 infection and sheds new light on developing novel chemoprophylaxis and chemotherapy against SARS-CoV-2.
Heat inactivation of the Severe Acute Respiratory Syndrome Coronavirus 2
Authors: Batéjat Christophe , Grassin Quentin , Manuguerra Jean-Claude , Leclercq India 
Published: May 2020

AbstractSupernatants of cells infected with SARS-CoV-2, nasopharyngeal and sera samples containing SARS-CoV-2 were submitted to heat inactivation for various periods of time, ranging from 30 seconds to 60 minutes. Our results showed that SARS-CoV-2 could be inactivated in less than 30 minutes, 15 minutes and 3 minutes at 56°C, 65°C and 95°C respectively. These data could help laboratory workers to improve their protocols with handling of the virus in biosafety conditions.
The transmembrane proteins M6 and Anakonda cooperate to initiate tricellular junction assembly in epithelia ofDrosophila
Authors: Wittek Anna , Hollmann Manuel , Schleutker Raphael , Luschnig Stefan 
Published: May 2020

SummaryCell vertices in epithelia comprise specialized tricellular junctions (TCJs) that seal the paracellular space between three adjoining cells [1, 2]. Although TCJs play fundamental roles in tissue homeostasis, pathogen defense, and in sensing tension and cell shape [3-5], how they are assembled, maintained and remodeled is poorly understood. InDrosophilathe transmembrane proteins Anakonda (Aka [6]) and Gliotactin (Gli [7]) are TCJ components essential for epithelial barrier formation. Additionally, the conserved four-transmembrane-domain protein M6, the only myelin proteolipid protein (PLP) family member inDrosophila, localizes to TCJs [8, 9]. PLPs associate with cholesterol-rich membrane domains and induce filopodia formation [10, 11] and membrane curvature [12], andDrosophila M6acts as a tumor suppressor [8], but its role in TCJ formation remained unknown. Here we show that M6 is essential for the assembly of tricellular, but not bicellular occluding junctions, and for barrier function in embryonic epithelia. M6 and Aka localize to TCJs in a mutually dependent manner and are jointly required for TCJ localization of Gli, whereas Aka and M6 localize to TCJs independently of Gli. Aka acts instructively and is sufficient to direct M6 to cell vertices in the absence of septate junctions, while M6 is required permissively to maintain Aka at TCJs. Furthermore, M6 and Aka are mutually dependent for their accumulation in a low-mobility pool at TCJs. These findings suggest a hierarchical model for TCJ assembly, where Aka and M6 promote TCJ formation through synergistic interactions that demarcate a distinct plasma membrane microdomain at cell vertices.
Impaired hand dexterity function in a non-human primate model with chronic Parkinson’s disease
Authors: Seo Jincheol , Won Jinyoung , Kim Keonwoo , Park Junghyung , Yeo Hyeon-Gu , Kim Yu Gyeong , Baek Seung Ho , Lee Hoonwon , Jeon Chang-Yeop , Choi Won Seok , Lee Sangil , Kim Ki Jin , Park Sung-Hyun , Son Yeonghoon , Jeong Kang Jin , Lim Kyung Seob , Kang Philyong , Lee Hwal-Yong , Son Hee-Chang , Huh Jae-Won , Kim Young-Hyun , Jin Yeung Bae , Lee Dong-Seok , Lee Sang-Rae , Choi Ji-Woong , Lee Youngjeon 
Published: May 2020

AbstractSymptoms of Parkinson’s disease (PD) caused by loss of dopaminergic neurons are accompanied by movement disorders, including tremors, rigidity, bradykinesia, and akinesia. Non-human primate (NHP) models with PD play an essential role in the analysis of PD pathophysiology and behavior symptoms. As impairments of hand dexterity function can affect activities of daily living in patients with PD, research on hand dexterity function in NHP models with chronic PD is essential. Traditional rating scales previously used in the evaluation of animal spontaneous behavior were insufficient due to factors related to subjectivity and passivity. Thus, experimentally designed applications for an appropriate apparatus are necessary. In this study, we aimed to longitudinally assess hand dexterity function using hand dexterity task (HDT) in NHP-PD models. To validate this assessment, we analyzed an alteration in Parkinsonian tremor symptoms, loss of dopaminergic neuron, and positron emission tomography (PET) imaging of dopamine transporters (DAT) in these models. HDT latency significantly increased in NHP-PD models. In addition, a significant inverse correlation between HDT and DAT was identified, but no local bias was found. The correlation with intention tremor symptoms was lower than the resting tremor. In conclusion, the evaluation of HDT may reflect behavioral symptoms of NHP-PD models. Furthermore, HDT was effectively used to experimentally distinguish intention tremors from other tremors.