bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid Evolution of Knockdown Resistance Haplotypes in Response to Pyrethroid Selection inAedes aegypti
Authors: Baltzegar Jennifer , Vella Michael , Gunning Christian , Vasquez Gissella , Astete Helvio , Stell Fred , Fisher Michael , Scott Thomas W. , Lenhart Audrey , Lloyd Alun L. , Morrison Amy , Gould Fred 
Published: April 2021

AbstractThis study describes the evolution ofknockdown resistance (kdr)haplotypes inAedes aegyptiin response to pyrethroid insecticide use over the course of 18 years in Iquitos, Peru. Based on the duration and intensiveness of sampling (∼10,000 samples), this is the most thorough study of kdr population genetics inAe. aegyptito date within a city. We provide evidence for the direct connection between programmatic citywide pyrethroid spraying and the increase in frequency of specifickdrhaplotypes by identifying two evolutionary events in the population. The relatively high selection coefficients, even under infrequent insecticide pressure, emphasizes how quickly populations can evolve. The observed rapid increase in frequency of resistance alleles might have been aided by the incomplete dominance of resistance-conferring alleles over corresponding susceptibility alleles. In addition to dramatic temporal shifts, spatial suppression experiments reveal that genetic heterogeneity existed not only at the citywide scale, but also on a very fine scale within the city.
The evolution of germ-soma specialization under different genetic and environmental effects
Authors: Tverskoi Denis , Gavrilets Sergey 
Published: April 2021

AbstractDivision of labor exists at different levels of biological organization - from cell colonies to human societies. One of the simplest examples of the division of labor in multicellular organisms is germ-soma specialization, which plays a key role in the evolution of organismal complexity. Here we formulate and study a general mathematical model exploring the emergence of germ-soma specialization in colonies of cells. We consider a finite population of colonies competing for resources. Colonies are of the same size and are composed by asexually reproducing haploid cells. Each cell can contribute to activity and fecundity of the colony, these contributions are traded-off. We assume that all cells within a colony are genetically identical but gene expression is affected by variation in the microenvironment experienced by individual cells. Through analytical theory and evolutionary agent-based modeling we show that the shape of the trade-off relation between somatic and reproductive functions, the type and extent of variation in within-colony microenvironment, and, in some cases, the number of genes involved, are important predictors of the extent of germ-soma specialization. Specifically, increasing convexity of the trade-off relation, the number of different environmental gradients acting within a colony, and the number of genes (in the case of random microenvironmental effects) promote the emergence of germ-soma specialization. Overall our results contribute towards a better understanding of the role of genetic, environmental, and microenvironmental factors in the evolution of germ-soma specialization.
Vaccine Hyporesponse Induced By Individual Antibiotic Treatment In Mice And Non-Human Primates Is Diminished Upon Recovery Of The Gut Microbiome
Authors: Swaminathan Gokul , Citron Michael , Xiao Jianying , Norton James E , Reens Abigail L , Topçuoğlu Begüm D. , Maritz Julia M , Lee Keun-Joong , Freed Daniel C , Weber Teresa M , White Cory H , Kadam Mahika , Spofford Erin , Bryant-Hall Erin , Salituro Gino , Kommineni Sushma , Liang Xue , Danilchanka Olga , Fontenot Jane A , Woelk Christopher H , Gutierrez Dario A , Hazuda Daria J , Hannigan Geoffrey D 
Published: April 2021

AbstractEmerging evidence demonstrates a connection between microbiome composition and suboptimal response to vaccines (vaccine hyporesponse). Harnessing the interaction between microbes and the immune system could provide novel therapeutic strategies for improving vaccine response. Currently we do not fully understand the mechanisms and dynamics by which the microbiome influences vaccine response. Using both mouse and non-human primate models, we report that short-term oral treatment with a single antibiotic (vancomycin) results in disruption of the gut microbiome and this correlates with a decrease in systemic levels of antigen-specific IgG upon subsequent parenteral vaccination. We further show that recovery of microbial diversity before vaccination prevents antibiotic-induced vaccine hyporesponse, and that the antigen specific IgG response correlates with the recovery of microbiome diversity. RNA-sequencing analysis of small intestine, spleen, whole blood, and secondary lymphoid organs from antibiotic treated mice revealed a dramatic impact on the immune system, and a muted inflammatory signature is correlated with loss of bacteria fromLachnospiraceae, Ruminococcaceae, andClostridiaceae. These results suggest that microbially modulated immune pathways may be leveraged to promote vaccine response and will inform future vaccine design and development strategies.ImportanceAntibiotic-induced gut microbiome disruption has been linked to reduced vaccine efficacy. Despite these observations, there remains a knowledge gap in the specific mechanisms by which antibiotics and the gut microbiome influence vaccine efficacy. We aim to contribute to the field’s growing mechanistic understanding by presenting a detailed analysis of antibiotic treatment and recovery as it relates to vaccine response and the microbiome. Using animal models, we show that short-term antibiotic treatment prior to vaccination results in diminished vaccine-specific immune responses, and that these are correlated with specific microbiome signatures. We also demonstrate the converse, in which gut microbiome recovery can result in improved vaccine response. We further reveal that antibiotics can significantly alter multiple relevant immune pathways and this alteration in immune tone may contribute to the vaccine hyporesponse. We expect our findings will enable the continued prosecution of the role of the microbiome in modulating the host immune system.
Taking aim at the perceptual side of motor learning: Exploring how explicit and implicit learning encode perceptual error information through depth vision
Authors: Campagnoli Carlo , Domini Fulvio , Taylor Jordan A. 
Published: April 2021

AbstractMotor learning in visuomotor adaptation tasks results from both explicit and implicit processes, each responding differently to an error signal. While the motor output side of these processes is extensively studied, their visual input side is relatively unknown. We investigated if and how depth perception affects the computation of error information by explicit and implicit motor learning. Two groups of participants threw virtual darts at a virtual dartboard while receiving perturbed endpoint feedback. The Delayed group was allowed to re-aim and their feedback was delayed to emphasize explicit learning, while the Clamped group received clamped cursor feedback which they were told to ignore, and continued to aim straight at the target to emphasize implicit adaptation. Both groups played this game in a highly detailed virtual environment (Depth condition) and in an empty environment (No-Depth condition). The Delayed group showed an increase in error sensitivity under Depth relative to No-Depth conditions. In contrast, the Clamped group adapted to the same degree under both conditions. The movement kinematics of the Delayed participants also changed under the Depth condition, consistent with the target appearing more distant, unlike the Clamped group. A comparison of the Delayed behavioral data with a perceptual task from the same individuals showed that the effect of the Depth condition on the re-aiming direction was consistent with an increase in the scaling of the error distance and size. These findings suggest that explicit and implicit learning processes may rely on different sources of perceptual information.New & NoteworthyWe leveraged a classic sensorimotor adaptation task to perform a first systematic assessment of the role of perceptual cues in the estimation of an error signal in the 3D space during motor learning. We crossed two conditions presenting different amounts of depth information, with two manipulations emphasizing explicit and implicit learning processes. Explicit learning responded to the visual conditions, consistent with perceptual reports, while implicit learning appeared to be independent of them.
Statistical properties of the MetaCore network of protein-protein interactions
Authors: Kotelnikova Ekaterina , Frahm Klaus M. , Lages José , Shepelyansky Dima L 
Published: April 2021

AbstractThe MetaCore commercial database describes interactions of proteins and other chemical molecules and clusters in the form of directed network between these elements, viewed as nodes. The number of nodes goes beyond 40 thousands with almost 300 thousands links between them. The links have essentially bi-functional nature describing either activation or inhibition actions between proteins. We present here the analysis of statistical properties of this complex network applying the methods of the Google matrix, PageRank and CheiRank algorithms broadly used in the frame of the World Wide Web, Wikipedia, the world trade and other directed networks. We specifically describe the Ising PageRank approach which allows to treat the bi-functional type of protein-protein interactions. We also show that the developed reduced Google matrix algorithm allows to obtain an effective network of interactions inside a specific group of selected proteins. This method takes into account not only direct protein-protein interactions but also recover their indirect nontrivial couplings appearing due to summation over all the pathways passing via the global bi-functional network. The developed analysis allows to espablish an average action of each protein being more oriented to activation or inhibition. We argue that the described Google matrix analysis represents an efficient tool for investigation of influence of specific groups of proteins related to specific diseases.
Focal fMRI signal enhancement with implantable inductively coupled detectors
Authors: Chen Yi , Wang Qi , Choi Sangcheon , Zeng Hang , Takahashi Kengo , Qian Chunqi , Yu Xin 
Published: April 2021

ABSTRACTDespite extensive efforts to increase the signal-to-noise ratio (SNR) of fMRI images for brain-wide mapping, technical advances of focal brain signal enhancement are lacking, in particular, for animal brain imaging. Emerging studies have combined fMRI with fiber optic-based optogenetics to decipher circuit-specific neuromodulation from meso to macroscales. Acquiring fMRI signal with high spatiotemporal resolution is needed to bridge cross-scale functional dynamics, but SNR of targeted cortical regions is a limiting factor. We have developed a multi-modal fMRI imaging platform with an implanted inductive coil detector. This detector boosts the tSNR of MRI images, showing a 2-3 fold sensitivity gain over conventional coil configuration. In contrast to the cryoprobe or array coils with limited spaces for implanted brain interface, this setup offers a unique advantage to study brain circuit connectivity with optogenetic stimulation and can be further extended to other multi-modal fMRI mapping schemes.
Autophagy Induced by Palmitic Acid: a Brake in NAFLD Neutrophils
Authors: Peng Zhicheng , Wang Heyuan , Hsu Alan Y. , Du Xiliang , Yang Yuchen , Fang Baochen , Li Yunfei , Zhu Yiwei , Song Yuxiang , Li Xiaobing , Wang Zhe , Li Xinwei , Liu Guowen 
Published: April 2021

AbstractInnate immune suppression and high blood fatty acid levels are the pathological basis of multiple metabolic diseases. Neutrophil vacuolation is an indicator of the immune status of patients, which is associated with autophagy-dependent granule degradation. Vacuolated neutrophils are observed in ethanol toxicity and septicemia patients due to the changes in their blood constituents, but how about the neutrophils in nonalcoholic fatty liver disease (NAFLD) patient is unknown. Here, we confirmed that an adhesion deficiency and an increased autophagy level existed in NAFLD neutrophils, and the three neutrophil granule subunits, namely, the azurophil granules, specific granules and gelatinase granules, could be engulfed by autophagosomes for degradation, and these autophagy-triggered granule degradation events were associated with vacuolation in palmitic acid (PA)-treated and NAFLD neutrophils. Concordantly, the adhesion-associated molecules CD11a, CD11b, CD18 and Rap1 on the three granule subunits were degraded during PA induced autophagy. Moreover, the cytosolic CD11a, CD11b, CD18 and Rap1 were targeted by Hsc70 and then delivered to lysosomal-like granules for degradation. Notably,in vitro and ex vivo, PA induced autophagy by inhibiting the p-PKCα/PKD2 pathway. Overall, we showed that high blood PA level inhibited the p-PKCα/PKD2 pathway to induce NAFLD neutrophil autophagy, which promoted the degradation of CD11a, CD11b, CD18 and Rap1 and further decreased the adhesion of neutrophils, thereby impairing the neutrophil function of NAFLD patients. This theory provides a new therapeutic strategy to improve the immune deficiency in NAFLD patients.Visual AbstractKey PointsVacuolation and adhesion deficiency of NAFLD neutrophils are associated with autophagy-dependent granule degradationPA inhibits p-PKCα/PKD2 to induce autophagy, which induces the degradation of CD11a, CD11b, CD18 and Rap1 and decreases neutrophil adhesion
Recovery from acute SARS-CoV-2 infection and development of anamnestic immune responses in T cell-depleted rhesus macaques
Authors: Hasenkrug Kim J. , Feldmann Friederike , Myers Lara , Santiago Mario L. , Guo Kejun , Barrett Bradley S. , Mickens Kaylee L. , Carmody Aaron , Okumura Atsushi , Rao Deepashri , Collins Madison M. , Messer Ronald J. , Lovaglio Jamie , Shaia Carl , Rosenke Rebecca , van Doremalen Neeltje , Clancy Chad , Saturday Greg , Hanley Patrick , Smith Brian , Meade-White Kimberly , Shupert W. Lesley , Hawman David W. , Feldmann Heinz 
Published: April 2021

AbstractSevere COVID-19 has been associated with T cell lymphopenia1,2, but no causal effect of T cell deficiency on disease severity has been established. To investigate the specific role of T cells in recovery from SARS-CoV-2 infections we studied rhesus macaques that were depleted of either CD4+, CD8+or both T cell subsets prior to infection. Peak virus loads were similar in all groups, but the resolution of virus in the T cell-depleted animals was slightly delayed compared to controls. The T cell-depleted groups developed virus-neutralizing antibody responses and also class-switched to IgG. When re-infected six weeks later, the T cell-depleted animals showed anamnestic immune responses characterized by rapid induction of high-titer virus-neutralizing antibodies, faster control of virus loads and reduced clinical signs. These results indicate that while T cells play a role in the recovery of rhesus macaques from acute SARS-CoV-2 infections, their depletion does not induce severe disease, and T cells do not account for the natural resistance of rhesus macaques to severe COVID-19. Neither primed CD4+or CD8+T cells appeared critical for immunoglobulin class switching, the development of immunological memory or protection from a second infection.
Ventral tegmental area glutamate neurons mediate the nonassociative consequences of traumatic stress
Authors: McGovern Dillon J. , Ecton Koy L. , Huynh David T. , Rau Andrew R. , Hentges Shane T. , Ly Annie , Baratta Michael V. , Root David H. 
Published: April 2021

SUMMARYExposure to trauma is a risk factor for the development of a number of mood disorders, and may enhance vulnerability to future adverse life events. Recent data implicate ventral tegmental area (VTA) glutamate neuronal activity as functionally important for signaling aversive or threating stimuli. However, it is unknown whether VTA glutamate neurons regulate transsituational outcomes that result from stress and whether these neurons are sensitive to stressor controllability. This work established an operant mouse paradigm to examine the impact of stressor controllability on VTA glutamate neuron function and stressor outcome. Uncontrollable (inescapable) stress, but not physically identical controllable (escapable) stress, produced social avoidance in male mice. Cell-type-specific calcium recordings showed that both controllable and uncontrollable stressors increased VTA glutamate neuronal activity. Chemogenetic reduction of VTA glutamate neuron activity prevented the behavioral sequelae of uncontrollable stress. Our results provide causal evidence that mice can be used to model stressor controllability and that VTA glutamate neurons may contribute to transsituational stressor outcomes, such as social avoidance and exaggerated fear that are observed within trauma-related disorders.
Sex differences in behavioral and brainstem transcriptomic neuroadaptations following neonatal opioid exposure in outbred mice
Authors: Borrelli Kristyn N. , Yao Emily J. , Yen Will W. , Ruan Qiu T. , Chen Melanie M. , Kelliher Julia C. , Langan Carly R. , Scotellaro Julia L. , Babbs Richard K. , Beierle Jacob C. , Logan Ryan W. , Johnson William Evan , Wachman Elisha M. , Cruz-Martín Alberto , Bryant Camron D. 
Published: April 2021

ABSTRACTThe opioid epidemic led to an increase in the number of Neonatal Opioid Withdrawal Syndrome (NOWS) cases in infants born to opioid-dependent mothers. Hallmark features of NOWS include weight loss, severe irritability, respiratory problems, and sleep fragmentation. Mouse models provide an opportunity to identify brain mechanisms that contribute to NOWS. Neonatal outbred Swiss Webster Cartworth Farms White (CFW) mice were administered morphine (15mg/kg, s.c.) twice daily for postnatal days (P) 1-14, an approximate of the third trimester of human gestation. Male and female mice underwent behavioral testing on P7 and P14 to determine the impact of opioid exposure on anxiety and pain sensitivity. Ultrasonic vocalizations (USVs) and daily body weights were also recorded. Brainstems containing pons and medulla were collected during morphine withdrawal on P14 for RNA-sequencing. Morphine induced weight loss from P2-14, which persisted during adolescence (P21) and adulthood (P50). USVs markedly increased at P7 in females, emerging earlier than males. On P7 and P14, both morphine exposed female and male mice displayed hyperalgesia on the hot plate and tail flick assays, with females having greater hyperalgesia than males. Morphine-exposed mice exhibited increased anxiety-like behavior in the open-field arena at P21. Transcriptome analysis of the brainstem (medulla plus pons), an area implicated in opioid withdrawal and NOWS, identified pathways enriched for noradrenergic signaling in females and males. We also found sex-specific pathways related to mitochondrial function and neurodevelopment in females and circadian entrainment in males. Sex-specific transcriptomic neuroadaptations implicate unique neurobiological mechanisms underlying NOWS-like behaviors.SIGNIFICANCE STATEMENTNeonatal opioid withdrawal syndrome (NOWS) is a poorly understood condition that has both a genetic and environmental component and is thought to be mechanistically distinct from opioid withdrawal in adults. The development of murine models for measuring neurobehavioral responses is critical for informing the neurobiological adaptations underlying NOWS. Using outbred mice that more closely model human genetic variation, we discovered a surprising degree of sexual dimorphism in behavioral timing and severity of NOWS-model behaviors as well as transcriptomic adaptations in brain tissue that together suggest distinct mechanisms and sex-specific therapeutics for reversing withdrawal symptoms and restoring brain function.
Detection of Junctional Ectopic Tachycardia by Central Venous Pressure
Authors: Tan Xin , Dai Yanwan , Humayun Ahmed Imtiaz , Chen Haoze , Allen Genevera I. , Jain Parag N. 
Published: April 2021

AbstractCentral venous pressure (CVP) is the blood pressure in the venae cavae, near the right atrium of the heart. This signal waveform is commonly collected in clinical settings, and yet there has been limited discussion of using this data for detecting arrhythmia and other cardiac events. In this paper, we develop a signal processing and feature engineering pipeline for CVP waveform analysis. Through a case study on pediatric junctional ectopic tachycardia (JET), we show that our extracted CVP features reliably detect JET with comparable results to the more commonly used electrocardiogram (ECG) features. This machine learning pipeline can thus improve the clinical diagnosis and ICU monitoring of arrhythmia. It also corroborates and complements the ECG-based diagnosis, especially when the ECG measurements are unavailable or corrupted.
Genomic and epigenomic adaptation in SP-R210 (Myo18A) isoform-deficient macrophages
Authors: Yau Eric , Chen Yan , Song Chunhua , Webb Jason , Carillo Marykate , Ikawasawa Yuka Imamura , Tang Zhenyuan , Takahashi Yoshinori , Umstead Todd M , Dovat Sinisa , Chroneos Zissis C. 
Published: April 2021

1AbstractMacrophages play fundamental roles in regulation of inflammatory responses to pathogens, resolution of inflammation and tissue repair, and maintenance of tissue homeostasis. The long (L) and short (S) isoforms of SP-R210/MYO18A, a macrophage receptor for surfactant protein A (SP-A) and C1q, regulate basal and inflammatory macrophage phenotype at multiple gene expression, translational, and subcellular levels in addition to their SP-A and C1q-mediated functions; disruption of L renders macrophages hyper-inflammatory, although the underlying mechanism had previously been unexplored. We asked whether disruption of the L isoform led to the hyper-inflammatory state via alteration of global genomic responses. RNA sequencing analysis of SP-R210L(DN) macrophages revealed basal and influenza induced upregulation of genes associated with inflammatory pathways, including TLR, RIG-I, NOD, and cytoplasmic DNA signaling, whereas knockdown of both SP-R210 isoforms (L and S) only resulted in increased RIG-I and NOD signaling. Chromatin immunoprecipitation sequencing (ChIP-seq) analysis showed increased genome-wide deposition of the pioneer transcription factor PU.1 in SP-R210L(DN) compared to WT cells. ChIP-seq analysis of histone H3 methylation showed alterations in both repressive (H3K9me3 and H3K27me3) and transcriptionally active (H3K9me3) histone marks. Influenza A virus (IAV) infection, which stimulates an array of cytosolic and TLR-mediated antiviral mechanisms, resulted in differential redistribution between proximal promoter and distal sites and decoupling of PU.1 binding from Toll-like receptor regulated gene promoters in SP-R210L(DN) cells. Our findings suggest that SP-R210L-deficient macrophages are poised with an open PU.1-primed chromatin conformation to rapidly respond to inflammatory and metabolic stimuli.