bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut-innervating nociceptor neurons protect against enteric infection by modulating the microbiota and Peyer’s patch microfold cells
Authors: Lai Nicole Y. , Musser Melissa A. , Pinho-Ribeiro Felipe A. , Baral Pankaj , Ma Pingchuan , Potts David E. , Chen Zuojia , Paik Donggi , Soualhi Salima , Shi Hailian , Misra Aditya , Goldstein Kaitlin , Sivanathan Kisha N. , Jacobson Amanda , Wallrapp Antonia , Lagomarsino Valentina , Kuchroo Vijay K. , Nowarski Roni , Starnbach Michael N. , Surana Neeraj K. , An Dingding , Wu Chuan , Huh Jun R. , Rao Meenakshi , Chiu Isaac M. 
Published: March 2019

SUMMARYGut-innervating nociceptor sensory neurons respond to noxious/tissue-damaging stimuli by initiating protective responses and releasing mediators that regulate tissue inflammation, gastrointestinal secretion, and motility. The role of nociceptors in host defense against enteric pathogens is unclear. Here, we found that gut-extrinsic nociceptor neurons are critical in protecting the host against Salmonella typhimurium (STm) infection. Nociceptors responded to STm by releasing the neuropeptide calcitonin gene-related peptide (CGRP). Targeted depletion of Nav1.8 and TRPV1 neurons from gut-extrinsic dorsal root ganglia and vagal ganglia increased STm colonization, invasion, and dissemination. Nociceptors regulated the gut microbiota at homeostasis, specifically segmented filamentous bacteria (SFB) levels in the ileum, which protected against STm by colonization resistance. Nociceptors also regulated the density of microfold epithelial cells in the Peyer’s patch via CGRP to limit points of entry for STm invasion into host tissues. Understanding how host sensory neurons crosstalk with pathogenic bacteria may impact treatments for enteric infections.HIGHLIGHTSNav1.8 and TRPV1 nociceptors defend against Salmonella typhimurium (STm) infectionNociceptors shape the gut microbiota and SFB levels which resist pathogen colonizationNociceptors suppress Peyer’s patch microfold cell density to limit pathogen invasionNeurons sense STm and release CGRP to modulate microfold cells and host defense
lionessR: single-sample network reconstruction in R
Authors: Kuijjer Marieke L. , Quackenbush John , Glass Kimberly 
Published: March 2019

SummaryWe recently developed LIONESS (Linear Interpolation to Obtain Network Estimates for Single Samples), a method that can be used together with network reconstruction algorithms to extract networks for individual samples in a population. LIONESS was originally made available as a function within the PANDA (Passing Attributes between Networks for Data Assimilation) regulatory network reconstruction framework. In this application note, we describe lionessR, an R implementation of LIONESS that can be applied to any network reconstruction method in R that outputs a complete, weighted adjacency matrix. As an example, we use lionessR to model single-sample co-expression networks on a bone cancer dataset, and show how lionessR can be used to identify differential co-expression between two groups of patients.Availability and implementationThe lionessR open source R package, which includes a vignette of the application, is freely available athttps://github.com/mararie/lionessR.Contactmarieke.kuijjer@ncmm.uio.no
Loss of microbial diversity and pathogen domination of the gut microbiota in critically ill patients
Authors: Ravi Anuradha , Halstead Fenella D , Bamford Amy , Casey Anna , Thomson Nicholas M. , van Schaik Willem , Snelson Catherine , Goulden Robert , Foster-Nyarko Ebenezer , Savva George M. , Whitehouse Tony , Pallen Mark J. , Oppenheim Beryl A. 
Published: March 2019

AbstractBackgroundFor long-stay patients on the adult intensive care unit, the gut microbiota plays a key role in determining the balance between health and disease. However, it remains unclear which ICU patients might benefit from interventions targeting the gut microbiota or the pathogens therein.MethodsWe undertook a prospective observational study of twenty-four ICU patients, in which serial faecal samples were subjected to shotgun metagenomic sequencing, phylogenetic profiling and microbial genome analyses.ResultsTwo-thirds of patients experienced a marked drop in gut microbial diversity (to an inverse Simpson’s index of <4) at some stage during their stay in ICU, often accompanied by absence or loss of beneficial commensal bacteria. Intravenous administration of the broad-spectrum antimicrobial agent meropenem was significantly associated with loss of gut microbial diversity, but administration of other antibiotics, including piperacillin-tazobactam, failed to trigger statistically detectable changes in microbial diversity. In three quarters of ICU patients, we documented episodes of gut domination by pathogenic strains, with evidence of cryptic nosocomial transmission ofEnterococcus faecium. In some patients we also saw domination of the gut microbiota by commensal organisms, such asMethanobrevibacter smithii.ConclusionsOur results support a role for metagenomic surveillance of the gut microbiota and pave the way for patient-specific interventions that maintain or restore gut microbial diversity in the ICU.
Population history from the Neolithic to present on the Mediterranean island of Sardinia: An ancient DNA perspective
Authors: Marcus Joseph H. , Posth Cosimo , Ringbauer Harald , Lai Luca , Skeates Robin , Sidore Carlo , Beckett Jessica , Furtwängler Anja , Olivieri Anna , Chiang Charleston , Al-Asadi Hussein , Dey Kushal , Joseph Tyler A. , Der Sarkissian Clio , Radzevičiūtė Rita , Gradoli Maria Giuseppina , Haak Wolfgang , Reich David , Schlessinger David , Cucca Francesco , Krause Johannes , Novembre John 
Published: March 2019

AbstractRecent ancient DNA studies of western Eurasia have revealed a dynamic history of admixture, with evidence for major migrations during the Neolithic and Bronze Age. The population of the Mediterranean island of Sardinia has been notable in these studies – Neolithic individuals from mainland Europe cluster more closely with Sardinian individuals than with all other present-day Europeans. The current model to explain this result is that Sardinia received an initial influx of Neolithic ancestry and then remained relatively isolated from expansions in the later Neolithic and Bronze Age that took place in continental Europe. To test this model, we generated genome-wide capture data (approximately 1.2 million variants) for 43 ancient Sardinian individuals spanning the Neolithic through the Bronze Age, including individuals from Sardinia’s Nuragic culture, which is known for the construction of numerous large stone towers throughout the island. We analyze these new samples in the context of previously generated genome-wide ancient DNA data from 972 ancient individuals across western Eurasia and whole-genome sequence data from approximately 1,500 modern individuals from Sardinia. The ancient Sardinian individuals show a strong affinity to western Mediterranean Neolithic populations and we infer a high degree of genetic continuity on the island from the Neolithic (around fifth millennium BCE) through the Nuragic period (second millennium BCE). In particular, during the Bronze Age in Sardinia, we do not find significant levels of the “Steppe” ancestry that was spreading in many other parts of Europe at that time. We also characterize subsequent genetic influx between the Nuragic period and the present. We detect novel, modest signals of admixture between 1,000 BCE and present-day, from ancestry sources in the eastern and northern Mediterranean. Within Sardinia, we confirm that populations from the more geographically isolated mountainous provinces have experienced elevated levels of genetic drift and that northern and southwestern regions of the island received more gene flow from outside Sardinia. Overall, our genetic analysis sheds new light on the origin of Neolithic settlement on Sardinia, reinforces models of genetic continuity on the island, and provides enhanced power to detect post-Bronze-Age gene flow. Together, these findings offer a refined demographic model for future medical genetic studies in Sardinia.
An image-computable model for the stimulus selectivity of gamma oscillations
Authors: Hermes Dora , Petridou Natalia , Kay Kendrick , Winawer Jonathan 
Published: March 2019

AbstractGamma oscillations in visual cortex have been hypothesized to be critical for perception, cognition, and information transfer. However, observations of these oscillations in visual cortex vary widely; some studies report little to no stimulus-induced narrowband gamma oscillations, others report oscillations for only some stimuli, and yet others report large oscillations for most stimuli. To reconcile these findings and better understand this signal, we developed a model that predicts gamma responses for arbitrary images and validated this model on electrocorticography (ECoG) data from human visual cortex. The model computes variance across the outputs of spatially pooled orientation channels, and accurately predicts gamma amplitude across 86 images. Gamma responses were large for a small subset of stimuli, differing dramatically from fMRI and ECoG broadband (non-oscillatory) responses. We suggest that gamma oscillations in visual cortex serve as a biomarker of gain control rather than being a fundamental mechanism for communicating visual information.
Identification of reduced host transcriptomic signatures for tuberculosis and digital PCR-based validation and quantification
Authors: Gliddon Harriet D. , Kaforou Myrsini , Alikian Mary , Habgood-Coote Dominic , Zhou Chenxi , Oni Tolu , Anderson Suzanne T. , Brent Andrew J. , Crampin Amelia C. , Eley Brian , Kern Florian , Langford Paul R. , Ottenhoff Tom H. M. , Hibberd Martin L. , French Neil , Wright Victoria J. , Dockrell Hazel M. , Coin Lachlan J. , Wilkinson Robert J. , Levin Michael ,   on behalf of the ILULU Consortium
Published: March 2019

AbstractRecently, host whole blood gene expression signatures have been identified for diagnosis of tuberculosis (TB). Absolute quantification of the concentrations of signature transcripts in blood have not been reported, but would facilitate the development of diagnostic tests.To identify minimal transcript signatures, we applied a novel transcript selection procedure to microarray data from African adults comprising 536 patients with TB, other diseases (OD) and latent TB (LTBI), divided into training and test sets. Signatures were validated using reverse transcriptase (RT) - digital PCR (dPCR).A four-transcript signature (GBP6, TMCC1, PRDM1, ARG1) measured using RT-dPCR distinguished TB patients from those with OD (area under the curve (AUC) 93.8% (CI95% 82.2 – 100%). A three-transcript signature (FCGR1A, ZNF296, C1QB) differentiated TB from LTBI (AUC 97.3%, CI95%: 93.3 – 100%), regardless of HIV.These signatures have been validated across platforms and across samples offering strong, quantitative support for their use as diagnostic biomarkers for TB.
TheC. elegansSET-2 histone methyltransferase maintains germline fate by preventing progressive transcriptomic deregulation across generations
Authors: Robert Valérie J. , Knutson Andrew K. , Rechtsteiner Andreas , Yvert Gaël , Strome Susan , Palladino Francesca 
Published: March 2019

AbstractChromatin factors contribute to germline maintenance by preserving a germline-appropriate transcriptional program. In the absence of the conserved histone H3 Lys4 (H3K4) methyltransferase SET-2,C. elegansgerm cells progressively lose their identity over generations, leading to sterility. How this transgenerational loss of fertility results from the absence of SET-2 is unknown. Here we performed expression profiling across generations on germlines from mutant animals lacking SET-2 activity. We found that gene deregulation occurred in 2 steps: a priming step in early generations progressing to loss of fertility in later generations. By performing Within-Class Analysis (WCA), a derivative of Principal Component Analysis, we identified transcriptional signatures associated with SET-2 inactivation, both at the priming step and later on during loss of fertility. Further analysis showed that repression of germline genes, derepression of somatic programs, and X-chromosome desilencing through interference with PRC2-dependent repression, are priming events driving loss of germline identity in the absence of SET-2. Decreasing expression of identified priming genes, including the C/EBP homologuecebp-1and TGF-β pathway components, was sufficient to delay the onset of sterility, suggesting that they individually contribute to the loss of germ cell fate. Altogether, our findings illustrate how the loss of a chromatin regulator at one generation can progressively deregulate multiple transcriptional and signaling programs, ultimately leading to loss of appropriate cell fate.
ThePax6master control gene initiates spontaneous retinal development via a self-organising Turing network
Authors: Grocott Timothy , Lozano-Velasco Estefania , Mok Gi Fay , Münsterberg Andrea E 
Published: March 2019

AbstractUnderstanding how complex organ systems are assembled from simple embryonic tissues is a major challenge. Across the animal kingdom a great diversity of visual organs are initiated by a ‘master control gene’ calledPax6, which is both necessary and sufficient for eye development1–6. Yet precisely howPax6achieves this deeply homologous function is poorly understood. Here we show that vertebratePax6interacts with a pair of morphogen-coding genes,Tgfb2andFst, to form a putative Turing network7, which we have computationally modelled. Computer simulations suggest that this gene network is sufficient to spontaneously polarise the developing retina, establishing the eye’s first organisational axis and prefiguring its further development. Our findings reveal how retinal self-organisation may be initiated independent of the highly ordered tissue interactions that help to assemble the eyein vivo. These results help to explain how stem cell aggregates spontaneously self-organise into functional eye-cupsin vitro8. We anticipate these findings will help to underpin retinal organoid technology, which holds much promise as a platform for disease modelling, drug development and regenerative therapies.
The crustaceanArmadillidium vulgare(Latreille, 1804) (Isopoda: Oniscoidea), a new promising model for the study of cellular senescence
Authors: Depeux Charlotte , Samba-Louaka Ascel , Becking Thomas , Braquart-Varnier Christine , Moreau Jérôme , Lemaître Jean-François , Laverre Tiffany , Paulhac Hélène , Dechaume-Moncharmont François-Xavier , Gaillard Jean-Michel , Beltran-Bech Sophie 
Published: March 2019

ABSTRACTSenescence, the decline of physiological parameters with increasing age, is a quasi-ubiquitous phenomenon in the living world. The observed patterns of senescence, however, can markedly differ across species and populations, between sexes, and even among individuals. To identify the drivers of this variation in senescence, experimental approaches are essential and involve the development of tools and new study models. Current knowledge of the senescence process is mostly based on studies on vertebrates and main information about senescence in invertebrates is mostly limited to model organisms such asCaenorhabditis elegansorDrosophila melanogaster. In this context, we tested whether biomarkers of vertebrate ageing could be used to study senescence in a new invertebrate model: the common woodlouseArmadillidium vulgare(Latreille, 1804). More specifically, we looked for the effect of age in woodlouse on three well-established physiological biomarkers of ageing in vertebrates: immune cells (cell size, density, and viability), β-galactosidase activity, and the gene expression of telomerase reverse transcriptase (TERT), an essential subunit of telomerase protein. We found that the size of immune cells was higher in older individuals, whereas their density and viability decreased, and that the β-galactosidase activity increased with age, whereas the TERT gene expression decreased. These findings demonstrate that woodlouse displays age-related changes in biomarkers of vertebrate senescence, with different patterns depending on gender. The tools used in studies of vertebrate senescence can thus be successfully used in studies of senescence of invertebrates such as the woodlouse. The application of commonly used tools to new biological models offers a promising approach to assess the diversity of senescence patterns across the tree of life.
Extensive memory testing improves prediction of progression to MCI in late middle age
Authors: Gustavson Daniel E. , Elman Jeremy A. , Sanderson-Cimino Mark , Franz Carol E. , Panizzon Matthew S. , Jak Amy J. , Reynolds Chandra A. , Neale Michael C. , Lyons Michael J. , Kremen William S. 
Published: March 2019

AbstractINTRODUCTIONPredicting risk for Alzheimer’s disease when most people are likely still biomarker negative would aid earlier identification. We hypothesized that combining multiple memory tests and scores in middle-aged adults would provide useful, and non-invasive, prediction of 6-year progression to MCI.METHODSWe examined 849 men who were cognitively normal at baseline (mean age=55.69±2.45).RESULTSCalifornia Verbal Learning Test learning trials was the best individual predictor of amnestic MCI (OR=4.75). A latent factor incorporating 7 measures across 3 memory tests provided much stronger prediction (OR=9.88). This compared favorably with biomarker-based prediction in a study of much older adults.DISCUSSIONNeuropsychological tests are sensitive and early indicators of Alzheimer’s disease risk at an age when few individuals are likely to have yet become biomarker positive. Single best measures may appear time- and cost-effective, but 30 additional minutes of testing, and use of multiple scores within tests, provides substantially improved prediction
microRNA mir-598-3p mediates susceptibility to stress-enhancement of remote fear memory
Authors: Jones Meghan E , Sillivan Stephanie E. , Jamieson Sarah , Rumbaugh Gavin , Miller Courtney A. 
Published: March 2019

ABSTRACTmicroRNAs (miRNAs) have emerged as potent regulators of learning, recent memory and extinction. However, our understanding of miRNAs directly involved in regulating complex psychiatric conditions perpetuated by aberrant memory, such as in posttraumatic stress disorder (PTSD), remains limited. To begin to address the role of miRNAs in persistent memory, we performed small-RNA sequencing on basolateral amygdala (BLA) tissue to identify miRNAs altered by auditory fear conditioning (FC) one month after training. mir-598-3p, a highly conserved miRNA previously unstudied in the brain, was downregulated in the BLA. Further decreasing BLA mir-598-3p levels did not alter the expression or extinction of the remote fear memory. Given that stress is a critical component in PTSD, we next assessed the impact of stress-enhanced fear learning (SEFL) on mir-598-3p levels, finding the miRNA is elevated in the BLA of male, but not female, mice susceptible to the effects of stress in SEFL. Accordingly, intra-BLA inhibition of mir-598-3p interfered with expression and extinction of the remote fear memory in male, but not female, mice. This effect could not be attributed to an anxiolytic effect of miRNA inhibition. Finally, bioinformatic analysis following quantitative proteomics on BLA tissue collected 30 days post-SEFL training identified putative mir-598-3p targets and related pathways mediating the differential susceptibility, with evidence for regulation of the actin cytoskeleton.
Levels of sdRNAs in cytoplasm and their association with ribosomes are dependent upon stress conditions but independent from snoRNA expression
Authors: Mleczko Anna M. , Machtel Piotr , Walkowiak M. , Wasilewska A. , Bąkowska-Żywicka K. 
Published: March 2019

ABSTRACTIn recent years, a number of small RNA molecules derived from snoRNAs have been observed. Findings concerning the functions of sdRNAs in cells are limited primarily to their involvement in microRNA pathways. However, similar molecules have been observed inSaccharomyces cerevisiae, which is an organism lacking miRNA machinery. Considering our previous observations, we examined the subcellular localization of sdRNAs in yeast. Our findings reveal that both sdRNAs and their precursors, snoRNAs, are present in the cytoplasm at levels dependent upon stress conditions. Moreover, both sdRNAs and snoRNAs interact with translating ribosomes in a stress-dependent manner. As a consequence of binding to ribosomes, yeast sdRNAs exhibit inhibitory activity on translation. However, observed levels of sdRNAs and snoRNAs in the cytoplasm and their association with ribosomes suggest independent regulation of these molecules by yet unknown factors.
Single trial dynamics of attentional intensity in visual area V4
Authors: Ghosh Supriya , Maunsell John H.R. 
Published: March 2019

ABSTRACTUnderstanding how activity of visual neurons represents distinct components of attention and their dynamics that account for improved visual performance remains elusive because single-unit experiments have not isolated the intensive aspect of attention from attentional selectivity. We isolated attentional intensity and its single trial dynamics as determined by spatially non-selective attentional performance in an orientation discrimination task while recording from neurons in monkey visual area V4. We found that attentional intensity is a distinct cognitive signal that can be distinguished from spatial selectivity, reward expectations and motor actions. V4 spiking on single trials encodes a combination of sensory and cognitive signals on different time scales. Attentional intensity and the detection of behaviorally relevant sensory signals are well represented, but immediate reward expectation and behavioral choices are poorly represented in V4 spiking. These results provide a detailed representation of perceptual and cognitive signals in V4 that are crucial for attentional performance.
The yeast proteases Ddi1 and Wss1 are both involved in the DNA replication stress response
Authors: Svoboda Michal , Konvalinka Jan , Trempe Jean-François , Saskova Klara Grantz 
Published: March 2019

AbstractGenome integrity and cell survival are dependent on proper replication stress response. Multiple repair pathways addressing obstacles generated by replication stress arose during evolution, and a detailed understanding of these processes is crucial for treatment of numerous human diseases. Here, we investigated the strong negative genetic interaction between two proteases involved in the DNA replication stress response, yeast Wss1 and Ddi1. While Wss1 proteolytically acts on DNA-protein crosslinks, mammalian DDI1 and DDI2 proteins remove RTF2 from stalled forksviaa proposed proteasome shuttle hypothesis. We show that the double-deleted Δddi1, Δwss1 yeast strain is hypersensitive to the replication drug hydroxyurea and that this phenotype can be complemented only by catalytically competent Ddi1 protease. Furthermore, our data show the key involvement of the helical domain preceding the Ddi1 protease domain in response to replication stress caused by hydroxyurea, offering the first suggestion of this domain’s biological function. Overall, our study provides a basis for a novel dual protease-based mechanism enabling yeast cells to counteract DNA replication stress.