bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaccine-induced ICOS+CD38+ cTfh are sensitive biosensors of age-related changes in inflammatory pathways
Authors: Herati Ramin Sedaghat , Silva Luisa Victoria , Vella Laura A. , Muselman Alexander , Alanio Cecile , Bengsch Bertram , Kurupati Raj K. , Kannan Senthil , Manne Sasikanth , Kossenkov Andrew V. , Canaday David H. , Doyle Susan A. , Ertl Hildegund C.J. , Schmader Kenneth E. , Wherry E. John 
Published: July 2019

AbstractHumoral immune responses are dysregulated with aging but details remain incompletely understood. In particular, little is known about the effects of aging on T follicular helper (Tfh) CD4 cells, the subset that provides critical help to B cells for effective humoral immunity. We previously demonstrated that influenza vaccination increases a circulating Tfh (cTfh) subset that expresses ICOS and CD38, contains influenza-specific memory cells, and is correlated with antibody responses. To directly study the effects of aging on the cTfh response, we performed transcriptional profiling and cellular analysis before and after influenza vaccination in young and elderly adults. Several key differences in cTfh responses were revealed in the elderly. First, whole blood transcriptional profiling defined cross-validated genesets of youth versus aging and these genesets were, compared to other T cells, preferentially enriched in ICOS+CD38+ cTfh from young and elderly subjects, respectively, following vaccination. Second, vaccine-induced ICOS+CD38+ cTfh from the elderly were enriched for transcriptional signatures of inflammation including TNF-NFkB pathway activation. Indeed, we reveal a paradoxical positive effect of TNF signaling on Tfh providing help to B cells linked to survival circuits that may explain detrimental effects of TNF blockade on vaccine responses. Finally, vaccine-induced ICOS+CD38+ cTfh displayed strong enrichment for signatures of underlying age-associated biological changes. Thus, these data reveal key biological changes in cTfh during aging and also demonstrate the sensitivity of vaccine-induced cTfh to underlying changes in host physiology. This latter observation suggests that vaccine-induced cTfh could function as sensitive biosensors of underlying inflammatory and/or overall immune health.One sentence summaryTranscriptional profiling of vaccine-induced circulating T follicular helper cell responding to influenza vaccination reveals age-associated effects on Tfh such as alterations in TNF-NFkB signaling.
How range residency and long-range perception change encounter rates
Authors: Martinez-Garcia Ricardo , Fleming Christen H. , Seppelt Ralf , Fagan William F. , Calabrese Justin M. 
Published: July 2019

AbstractEncounter rates link movement strategies to intra- and inter-specific interactions, and therefore translate individual movement behavior into higher-level ecological processes. Indeed, a large body of interacting population theory rests on the law of mass action, which can be derived from assumptions of Brownian motion in an enclosed container with exclusively local perception. These assumptions imply completely uniform space use, individual home ranges equivalent to the population range, and encounter dependent on movement paths actually crossing. Mounting empirical evidence, however, suggests that animals use space non-uniformly, occupy home ranges substantially smaller than the population range, and are often capable of nonlocal perception. Here, we explore how these empirically supported behaviors change pairwise encounter rates. Specifically, we derive novel analytical expressions for encounter rates under Ornstein-Uhlenbeck motion, which features non-uniform space use and allows individual home ranges to differ from the population range. We compare OU-based encounter predictions to those of Reflected Brownian Motion, from which the law of mass action can be derived. For both models, we further explore how the interplay between the scale of perception and home range size affects encounter rates. We find that neglecting realistic movement and perceptual behaviors can systematically bias encounter rate predictions.
HdaB: a novel and conserved DnaA-related protein that targets the RIDA process to stimulate replication initiation
Authors: Frandi Antonio , Collier Justine 
Published: July 2019

ABSTRACTExquisite control of the DnaA initiator is critical to ensure that bacteria initiate chromosome replication in a cell cycle-coordinated manner. In many bacteria, the DnaA-related and replisome-associated Hda/HdaA protein interacts with DnaA to trigger the regulatory inactivation of DnaA (RIDA) and prevent over-initiation events. In theC. crescentus Alphaproteobacterium, the RIDA process also targets DnaA for its rapid proteolysis by Lon. The impact of the RIDA process on adaptation of bacteria to changing environments remains unexplored. Here, we identify a novel and conserved DnaA-related protein, named HdaB, and show that homologs from three differentAlphaproteobacteriacan inhibit the RIDA process, leading to over-initiation and cell death when expressed in actively growingC. crescentuscells. We further show that HdaB interacts with HdaAin vivo, most likely titrating HdaA away from DnaA. Strikingly, we find that HdaB accumulates mainly during stationary phase and that it shortens the lag phase upon exit from stationary phase. Altogether, these findings suggest that expression ofhdaBduring stationary phase prepares cells to restart the replication of their chromosome as soon as conditions improve, a situation often met by free-living or facultative intracellularAlphaproteobacteria.
Genetic algorithm-based personalized models of human cardiac action potential
Authors: Smirnov D.N. , Syunyaev R.A. , Deviatiiarov R.M. , Gusev O.A. , Aras K.K. , Koppel A.C. , Efimov I.R. 
Published: July 2019

AbstractWe present a novel genetic algorithm-based solution to determine the set of cardiomyocyte model parameters based on experimental human action potential (AP) recordings. The novel approach is based on AP waveform dependence on the heart rate. In order to find the steady-state solution, optimized parameters include conductivities of ionic channels and exchangers augmented by slow variables, intracellular sodium concentration and sarcoplasmic reticulum calcium load. The algorithm is enhanced by a novel mutation operator, based on Cauchy distribution along a random direction in parameter space. We also demonstrate that increasing the number of elite organisms up to 7% results in faster convergence. Test runs indicate that algorithm error is below 5% for IKr, 7% for IK1and INaand 13% for ICaL. Experimental signal-to-noise ratio above 28 dB was sufficient for high quality algorithm performance. The algorithm validation using optical mapping recordings of human ventricular AP demonstrated low error that was below 6 mV for AP waveform and less than 16 ms for AP duration. Further validation of the personalized models was done using mRNA expression profile of two donor hearts. The mRNA-based model reproduced AP waveform dependence on cycle length with 13 mV accuracy and AP duration with 20 ms accuracy.
Rapid dissolution of dioecy by experimental evolution
Authors: Cossard G. G. , Gerchen J. F. , Li X. , Cuenot Y. , Pannell J. R. 
Published: July 2019

AbstractEvolutionary transitions from hermaphroditism to dioecy have been frequent in flowering plants, but recent analysis indicates that reversions from dioecy to hermaphroditism have also been common. Here, we use experimental evolution to expose a mechanism for such reversions. We removed males from dioecious populations of the wind-pollinated plant Mercurialis annua and allowed natural selection to act on the remaining females that varied in their propensity for the occasional production of male flowers; such ‘leaky’ sex expression is common in both males and females of dioecious plants. Over only four generations, females evolved a 23-fold increase in average male-flower production. The phenotypic masculinization of females was also sufficient to render them effective at siring progeny in the presence of males. Our study illustrates the rapid dissolution of dioecy and the evolution of functional hermaphroditism under conditions that may frequently occur during periods of low population density, repeated colonization, or range expansion. It thereby experimentally validates a mechanism for a major transition in plant sexual systems..
Cortical selectivity driven by connectivity: Innate connectivity patterns of the visual word form area
Authors: Li Jin , Osher David E. , Hansen Heather A. , Saygin Zeynep M. 
Published: July 2019

AbstractWhat determines the functional organization of cortex? One hypothesis is that innate connectivity patterns set up a scaffold upon which functional specialization can later take place. We tested this hypothesis by asking whether the visual word form area (VWFA), an experience-driven region, was already connected to proto language networks in neonates scanned within one week of birth. With resting-state fMRI, we found that neonates showed adult-like functional connectivity, and observed that i) language regions connected more strongly with the putative VWFA than other adjacent ventral visual regions that also show foveal bias, and ii) the VWFA connected more strongly with frontotemporal language regions than with regions adjacent to these language regions. These data suggest that the location of the VWFA is earmarked at birth due to its connectivity with the language network, providing evidence that innate connectivity instructs the later refinement of cortex.
The Genetic History of France
Authors: Pierre Aude Saint , Giemza Joanna , Karakachoff Matilde , Alves Isabel , Amouyel Philippe , Dartigues Jean-François , Tzourio Christophe , Monteil Martial , Galan Pilar , Hercberg Serge , Redon Richard , Génin Emmanuelle , Dina Christian 
Published: July 2019

ABSTRACTThe study of the genetic structure of different countries within Europe has provided significant insights into their demographic history and their actual stratification. Although France occupies a particular location at the end of the European peninsula and at the crossroads of migration routes, few population genetic studies have been conducted so far with genome-wide data. In this study, we analyzed SNP-chip genetic data from 2 184 individuals born in France who were enrolled in two independent population cohorts. Using FineStructure, six different genetic clusters of individuals were found that were very consistent between the two cohorts. These clusters match extremely well the geography and overlap with historical and linguistic divisions of France. By modeling the relationship between genetics and geography using EEMS software, we were able to detect gene flow barriers that are similar in the two cohorts and corresponds to major French rivers or mountains. Estimations of effective population sizes using IBDNe program also revealed very similar patterns in both cohorts with a rapid increase of effective population sizes over the last 150 generations similar to what was observed in other European countries. A marked bottleneck is also consistently seen in the two datasets starting in the fourteenth century when the Black Death raged in Europe. In conclusion, by performing the first exhaustive study of the genetic structure of France, we fill a gap in the genetic studies in Europe that would be useful to medical geneticists but also historians and archeologists.
Template Switching Mediates Contractions of a Repetitive Coding Region inS. cerevisiae
Authors: Stewart Taylor , Exner Alexandra E. , Patnaik Paras , Fuchs Stephen M. 
Published: July 2019

ABSTRACTThe C-terminal domain (CTD) is an essential domain of the largest subunit of RNA polymerase II, Rpb1p, and is composed of 26 tandem repeats of a seven-amino acid sequence, YSPTSPS. Despite being an essential domain within an essential gene, we have previously demonstrated that the CTD coding region is genetically unstable. Furthermore, yeast with a truncated or mutated CTD sequence are capable of promoting spontaneous genetic expansion or contraction of this coding region to improve fitness. We investigated the mechanism by which the CTD contracts using a tet-off reporter system forRPB1to monitor genetic instability within the CTD coding region. We report that contractions require the post-replication repair factor Rad5p but, unlike expansions, not the homologous recombination factors Rad51p and Rad52p. Sequence analysis of contraction events reveals that deleted regions are flanked by microhomologies. We also find that G-quadruplex forming sequences predicted by the QGRS Mapper are enriched on the noncoding strand of the CTD compared to the body ofRPB1. Formation of G-quadruplexes in the CTD coding region could block the replication fork, necessitating post-replication repair by template switching. We propose that contractions of the CTD result when microhomologies misalign during Rad5p-dependent template switching via fork reversal.
Broadband slow-wave modulation in posterior and anterior cortex tracks distinct states of propofol-induced unconsciousness
Authors: Stephen Emily P. , Hotan Gladia C. , Pierce Eric T. , Harrell P. Grace , Walsh John L. , Brown Emery N. , Purdon Patrick L. 
Published: July 2019

A controversy 5 has developed in recent years over the role that frontal and posterior cortices play in mediating consciousness and unconsciousness. One hypothesis proposes that posterior sensory and association cortices are the principal mediators of consciousness, citing evidence that strong slow-wave activity over posterior cortex during sleep disrupts the contents of dreaming. A competing hypothesis proposes that frontal-posterior interactions are critical to ignite a conscious percept, since activation of frontal cortex appears necessary for perception and can reverse unconsciousness under anesthesia. In both cases, EEG slow-waves (< 1 Hz) are considered evidence that up- and down-states are disrupting cortical activity necessary for consciousness. Here, we used anesthesia to study the interaction between the slow-wave and higher frequency activity in humans. If slow-waves are derived from underlying up and down-states, then they should modulate activity across a broad range of frequencies. We found that this broadband slow-wave modulation does occur: broadband slow-wave modulation occurs over posterior cortex when subjects initially become unconscious, but later encompasses both frontal and posterior cortex when subjects are more deeply anesthetized and likely unarousable. Based on these results, we argue that unconsciousness under anesthesia comprises several shifts in brain state that disrupt the sensory contents of consciousness distinct from arousal and awareness of those contents.Significance StatementThe roles of frontal and posterior cortices in mediating consciousness and unconsciousness are controversial. Disruption of posterior cortex during sleep appears to suppress the contents of dreaming, yet activation of frontal cortex appears necessary for perception and can reverse unconsciousness under anesthesia. We studied the time course of regional cortical disruption, as mediated by slow-wave modulation of broadband activity, during anesthesia-induced unconsciousness in humans. We found that broadband slow-wave modulation covered posterior cortex when subjects initially became unconscious, but later encompassed both frontal and posterior cortex when subjects were deeply anesthetized and likely unarousable. This suggests that unconsciousness under anesthesia comprises several shifts in brain state that disrupt the contents of consciousness distinct from arousal and awareness of those contents.
A Halo of Reduced Dinoflagellate Abundances In and Around Eelgrass Beds
Authors: Jacobs-Palmer Emily , Gallego Ramón , Ramón-Laca Ana , Kunselman Emily , Cribari Kelly , Horwith Micah , Kelly Ryan P. 
Published: July 2019

ABSTRACTSeagrass beds provide a variety of ecosystem services, both within and outside the bounds of the habitat itself. Here we use environmental DNA (eDNA) amplicons to analyze a broad cross-section of taxa from ecological communities in and immediately surrounding eelgrass (Zostera marina). Sampling seawater along transects extending alongshore outward from eelgrass beds, we demonstrate that eDNA provides meter-scale resolution of communities in the field. We evaluate eDNA abundance indices for thirteen major phylogenetic groups of marine and estuarine taxa along these transects, finding highly local changes linked with proximity to Z. marina for a diverse group of dinoflagellates, and for no other group of taxa. Eelgrass habitat is consistently associated with dramatic reductions in dinoflagellate abundance both within the contiguous beds and for at least fifteen meters outside, relative to nearby sites without eelgrass. These results are consistent with the hypothesis that eelgrass-associated communities have allelopathic effects on dinoflagellates, and that these effects can extend in a halo beyond the bounds of the contiguous beds. Because many dinoflagellates are capable of forming Harmful Algal Blooms (HABs) toxic to humans and other animal species, the apparent salutary effect of eelgrass habitat on neighboring waters has important implications for public health as well as shellfish aquaculture and harvesting.
Urbilaterian origin and evolution of sNPF-type neuropeptide signalling
Authors: Yañez-Guerra Luis Alfonso , Zhong Xingxing , Moghul Ismail , Butts Thomas , Zampronio Cleidiane G. , Jones Alexandra M. , Mirabeau Olivier , Elphick Maurice R. 
Published: July 2019

AbstractPhysiology and behaviour are controlled by neuropeptide signalling systems comprising peptide ligands and cognate receptors. Molecular phylogenetics combined with experimental identification of neuropeptide-receptor pairs has revealed that many neuropeptide signalling systems originated in the urbilaterian common ancestor of protostomes and deuterostomes. Neuropeptide-Y/neuropeptide-F (NPY/NPF)-type signalling is one such example, whereas NPY/NPF-related short-NPF (sNPF)-type signalling has hitherto only been identified in protostomes. Here we report the discovery of a neuropeptide (pQDRSKAMQAERTGQLRRLNPRF-NH2) that is the ligand for an sNPF-type receptor in a deuterostome, the starfish Asterias rubens (Phylum Echinodermata). Informed by phylogenetic analysis of sequence data, we conclude that the paralogous NPY/NPF-type and sNPF-type signalling systems originated in Urbilateria but NPY/NPF-type signalling was lost in echinoderms. Furthermore, we present evidence that sNPF-type peptides are orthologs of vertebrate prolactin-releasing peptides. Our findings demonstrate the importance of experimental studies on echinoderms for reconstructing the evolutionary history of neuropeptide signalling systems.
Genome-wide analysis identifies cis-acting elements regulating mRNA polyadenylation and translation during vertebrate oocyte maturation
Authors: Yang Fei , Wang Wei , Cetinbas Murat , Sadreyev Ruslan I. , Blower Michael D. 
Published: July 2019

AbstractChanges in gene expression are required to orchestrate changes in cell state during development. Most cells change patterns of gene expression through transcriptional regulation. In contrast, oocytes are transcriptionally silent and use changes in mRNA poly-A tail length to control protein production. Poly-A tail length is positively correlated with translation activation during early development. However, it is not clear how poly-A tail changes affect mRNA translation at a during vertebrate oocyte maturation. We used Tail-seq and polyribosome analysis to measure poly-A tail and translational changes during oocyte maturation in Xenopus laevis. We identified large-scale poly-A and translational changes during oocyte maturation and found that poly-A tail changes precede translation changes. Additionally, we identified a family of U-rich sequence elements that are enriched near the polyadenylation signal of polyadenylated and translationally activated mRNAs. A modest density of U-rich elements was correlated with polyadenylation while a high density of U-rich elements was required to activate translation, showing that polyadenylation and translation activation can be uncoupled. Collectively, our data show that changes in mRNA polyadenylation are a key mechanism regulating protein expression during vertebrate oocyte maturation and that these changes are controlled by a spatial code of cis-acting sequence elements. Our results provide insight into mechanisms of translational control in oocytes and identify novel proteins important for the completion of meiosis.
Fungal seed pathogens of wild chili peppers possess multiple mechanisms to tolerate capsaicinoids
Authors: Adams Catharine A. , Zimmerman Kolea , Fenstermacher Kristi , Thompson Mitchell G. , Skyrud Will , Behie Scott , Pringle Anne 
Published: July 2019

AbstractThe wild chili pepper Capsicum chacoense produces the spicy defense compounds known as capsaicinoids, including capsaicin and dihydrocapsaicin, antagonistic to the growth of fungal pathogens. Compared to other microbes, fungi isolated from infected seeds of C. chacoense possess much higher tolerance to these spicy compounds, having their growth slowed, but not entirely inhibited. Previous research has shown capsaicinoids inhibit microbes by disrupting ATP production via the binding of NADH dehydrogenase in the Electron Transport Chain (ETC), throttling Oxidative Phosphorylation (OXPHOS). Capsaicinoids may also disrupt cell membranes. Here, we investigated capsaicinoid tolerance in fungal seed pathogens isolated from C. chacoense. We selected 16 fungal isolates from four Ascomycete genera (Alternaria, Colletotrichum, Fusarium and Phomopsis). Using relative growth rate as a readout for tolerance, fungi were challenged with ETC inhibitors to infer if fungi possess alternative respiratory enzymes, and if effects on the ETC fully explained inhibition by capsaicinoids. In all isolates, we found evidence for at least one alternative NADH dehydrogenase. In many isolates we also found evidence for an alternative oxidase. These data suggest wild plant pathogens may be a rich source of alternative respiratory enzymes. We further demonstrate these fungal isolates are capable of the breakdown of capsaicinoids. Lastly, we determine the OXPHOS theory weakly explains the primary mechanism by which dihydrocapsaicin slows fungal growth, but not capsaicin. Our findings suggest capsaicinoids likely disrupt membranes in addition to energy poisoning, with implications for microbiology and human health.ImportancePlants make chemical compounds to protect themselves. For example, chili peppers produce the spicy compound capsaicin to inhibit animal feeding and pathogen damage. In humans, capsaicin binds to a membrane channel protein, creating the sensation of heat, while in microbes, capsaicin limits energy production by binding respiratory enzymes. However, some data suggest capsaicin also disrupts membranes. Here we studied fungal pathogens (Alternaria, Colletotrichum, Fusarium, and Phomopsis) isolated from a wild chili pepper, Capsicum chacoense. By measuring growth rate in the presence of antibiotics with known respiratory targets, we infer wild plant pathogens may be rich with alternative respiratory enzymes. A zone of clearance around the colonies, as well as LCMS data, further indicate these fungi can break down capsaicin. Lastly, the total inhibitory effect of capsaicin was not fully explained by its effect on respiratory enzymes. Our findings lend credence to studies proposing capsaicin may disrupt cell membranes, with implications for microbiology as well as human health.