bluuebunny/crossref_metadata_2025_split huggingface dataset:
Taste Bud Connectome: Implications for Taste Information Processing
Authors: Wilson Courtney E. , Lasher Robert S. , Yang Ruibiao , Dzowo Yannick , Kinnamon John C. , Finger Thomas E. 
Published: April 2021

AbstractTaste buds contain 3 types of morphologically identifiable mature cells, 2 of which mediate transduction of specific taste qualities: Type III cells transduce sour while Type II cells transduce either sweet, bitter or umami. A long-standing controversy is whether the nerve fibers innervating these cells are wired specifically, in a labeled-line fashion, or non-specifically, leading to broad responsiveness across taste qualities, the so-called across-fiber system of encoding. Using serial blockface scanning electron microscopy through 5 circumvallate mouse taste buds, we reconstructed the patterns of connectivity of nerve fibers as well as the degree of potential interaction between the two types of taste transducing cells. Type II and Type III cells share few points of contact with one another, and display no morphologically identifiable synapses, suggesting limited direct interaction between these cell types. Of the 127 nerve fibers that make synaptic contacts with taste cells in the sampling volume, about 70% (n=91) synapse with only one taste cell. Of the remaining 36 fibers, 4 synapse with both Type II and Type III cells, the remainder synapsing exclusively with multiple Type II taste cells or multiple Type III cells. Since Type II and Type III cells transduce different taste qualities, the few mixed fibers do not follow a labeled-line organization according to taste quality information and show that connectional specificity in taste buds is not absolute.Significance StatementTaste buds, the sensory end organs for the sense of taste, contain multiple types of sensory cells, with each responding to one of the primary tastes: salt, sweet, sour, bitter and umami. A long-standing question is whether each type of taste cell is wired specifically to a unique set of nerve fibers conveying a “labeled-line” message to the brain. Using serial sections, we determined the neural connectivity in mouse circumvallate taste buds. The majority of individual nerve fibers connect to a single type of taste cell, but 3.1% of the fibers branch to receive input from taste cells known to have different specificities. Thus taste cannot entirely be carried along nerve fibers dedicated to single taste qualities.
The genetics of assisted gene flow: immediate costs and long-term benefits
Authors: Grummer Jared A. , Booker Tom R. , Matthey-Doret Remi , Nietlisbach Pirmin , Thomaz Andréa T. , Whitlock Michael C. 
Published: April 2021

ABSTRACTPlant and animal populations are facing several novel risks such as human-mediated habitat fragmentation and climate change that threaten their long-term productivity and persistence. With the genetic health of many populations deteriorating due to climate change outpacing physiological adaptation, human interventions in the form of assisted gene flow (AGF) may provide genetic variation to adapt populations to predicted climate change scenarios and result in more robust and productive populations. We ran genetic simulations to mimic a variety of AGF scenarios and measured their outcomes on population-level fitness to answer the question: in which circumstances is it worthwhile to perform AGF? Based on the parameters we explored, AGF may be harmful in certain situations over the short term (e.g., the first ∼10-20 generations), due to outbreeding depression and introducing deleterious genetic variation. Moreover, under many parameter sets, the benefits of AGF were relatively weak or took many generations to accrue. In general, when the adaptive trait is controlled by many loci of small effect, the benefits of assisted gene flow take much longer to realize–potentially too long for most climate-related management decisions. We also show that when translocation effort is divided across several generations and outbreeding depression is strong, the recipient population experiences a smaller decrease in fitness as compared to moving all individuals in a single effort. Importantly, in most cases, we show that the genomic integrity of the recipient population remains relatively intact following AGF; the amount of genetic material from the donor population typically ends up constituting no more of the recipient population’s genome than the fraction introduced. Our results will be useful for conservation practitioners and silviculturists, for instance, aiming to intervene and adaptively manage so that populations maintain a robust genetic health and maintain productivity into the future given anthropogenic climate change.
The Backbone Network of Dynamic Functional Connectivity
Authors: Asadi Nima , Olson Ingrid R. , Obradovic Zoran 
Published: April 2021

1.AbstractTemporal networks have become increasingly pervasive in many real-world applications, including the functional connectivity analysis of spatially separated regions of the brain. A major challenge in analysis of such networks is the identification of noise confounds, which introduce temporal ties that are non-essential, or links that are formed by chance due to local properties of the nodes. Several approaches have been suggested in the past for static networks or temporal networks with binary weights for extracting significant ties whose likelihood cannot be reduced to the local properties of the nodes. In this work, we propose a data-driven procedure to reveal the irreducible ties in dynamic functional connectivity of resting state fRMI data with continuous weights. This framework includes a null model that estimates the latent characteristics of the distributions of temporal links through optimization, followed by a statistical test to filter the links whose formation can be reduced to the activities and local properties of their interacting nodes. We demonstrate the benefits of this approach by applying it to a resting state fMRI dataset, and provide further discussion on various aspects and advantages of it.
Estimating parameters of a stochastic cell invasion model with fluorescent cell cycle labelling using Approximate Bayesian Computation
Authors: Carr Michael J , Simpson Matthew J , Drovandi Christopher 
Published: April 2021

AbstractWe develop a parameter estimation method based on approximate Bayesian computation (ABC) for a stochastic cell invasion model using fluorescent cell cycle labeling with proliferation, migration, and crowding effects. Previously, inference has been performed on a deterministic version of the model fitted to cell density data, and not all the parameters were identifiable. Considering the stochastic model allows us to harness more features of experimental data, including cell trajectories and cell count data, which we show overcomes the parameter identifiability problem. We demonstrate that, whilst difficult to collect, cell trajectory data can provide more information about the parameters of the cell invasion model. To handle the intractability of the likelihood function of the stochastic model, we use an efficient ABC algorithm based on sequential Monte Carlo. Rcpp and MATLAB implementations of the simulation model and ABC algorithm used in this study are available athttps://github.com/michaelcarr-stats/FUCCI.
Forecasting the effects of water regulation on the population viability of a threatened amphibian
Authors: Mathwin Rupert , Wassens Skye , Gibbs Matthew S. , Young Jeanne , Ye Qifeng , Saltré Frédérik , Bradshaw Corey J.A. 
Published: April 2021

AbstractThe regulation of river systems alters hydrodynamics and often reduces lateral connectivity between river channels and floodplains. For taxa such as frogs that rely on floodplain wetlands to complete their lifecycle, decreasing inundation frequency can reduce recruitment and increase the probability of local extinction. We virtually reconstructed the inundation patterns of wetlands under natural and regulated flow conditions and built stochastic population models to quantify the probability of local extinction under different inundation scenarios. Specifically, we explored the interplay of habitat size, inundation frequency, and successive dry years on the local extinction probability of the threatened southern bell frogLitoria raniformisin the Murray River floodplains of South Australia. We hypothesised that the changes to wetland inundation resulting from river regulation are a principal driver ofL. raniformisdeclines in this semi-arid system.Regulation has reduced the inundation frequency of essential habitats below critical thresholds for the persistence of many fresh water-dependent species. Successive dry years raise the probability of local extinction, and these effects are strongest in smaller wetlands. Larger wetlands and those with more frequent average inundation are less susceptible to these effects.Elucidating these trends informs the prioritisation of treatment sites and the frequency of conservation interventions. Environmental water provision (through pumping or the operation of flow-regulating structures) is a promising tool to reduce the probability of breeding failure and local extinction. Our modelling approach can be used to prioritise the delivery of environmental water toL. raniformisand potentially many other frog species.
Daily rhythms in the transcriptomes of the human parasite Schistosoma mansoni
Authors: Rawlinson Kate A. , Reid Adam J. , Lu Zhigang , Driguez Patrick , Wawer Anna , Coghlan Avril , Sankaranarayanan Geetha , Buddenborg Sarah Kay , Soria Carmen Diaz , McCarthy Catherine , Holroyd Nancy , Sanders Mandy , Hoffmann Karl , Wilcockson David , Rinaldi Gabriel , Berriman Matt 
Published: April 2021

AbstractBackgroundThe consequences of the earth’s daily rotation have led to 24-hour biological rhythms in most organisms. Even parasites have daily rhythms, which, when in synchrony with host rhythms, optimize their fitness. Understanding these rhythms may enable development of novel control strategies that take advantage of rhythmic vulnerabilities. Recent work on blood-dwelling protozoan parasites has revealed daily rhythms in gene expression, physiology, drug sensitivity and the presence of an intrinsic circadian clock. However, similar studies on metazoan parasites are lacking. The aims of this study were to investigate if a metazoan parasite has daily molecular oscillations, whether they give us insight into how these longer-lived organisms can survive host daily cycles over a life-span of many years and to determine whether canonical metazoan circadian clock genes are present and rhythmic. We addressed these questions using the human blood fluke Schistosoma mansoni, that lives in the vasculature for decades and causes the serious neglected tropical disease schistosomiasis.ResultsUsing round-the-clock transcriptomics of male and female adult worms we discovered that ∼2% of its genes followed a daily pattern of expression. Rhythmic processes included a night-time stress response and a day-time metabolic ‘rush hour’. Transcriptional profiles in the female reproductive system were mirrored by daily patterns in egg laying (eggs are the main drivers of the host pathology). Genes cycling with the highest amplitudes include drug targets and a vaccine candidate. These 24hr rhythms may be driven by host rhythms and/or generated by a circadian clock. However, core clock genes are missing and orthologues of secondary clock genes show no 24hr rhythmicity in transcript abundance.ConclusionsThe daily rhythms identified here reveal temporally compartmentalised internal processes and host interactions over the daily cycle, including processes relevant to within-host survival and between-host transmission. Our findings suggest that if these daily rhythms are generated by an intrinsic circadian clock then the oscillatory mechanism must be distinct from that in other Metazoa. Most importantly, knowing which gene transcripts oscillate at this temporal scale is relevant to functional genomic studies that will lead to the development and delivery of therapeutics against schistosomiasis.
Musical experience partially counteracts temporal speech processing deficits in mild cognitive impairment
Authors: Price Caitlin N. , Bidelman Gavin M. 
Published: April 2021

ABSTRACTMild cognitive impairment (MCI) commonly impacts older adults resulting in more rapid cognitive and behavioral declines than typical aging. Individuals with MCI can exhibit impaired receptive speech abilities that may reflect neurophysiological changes in auditory-sensory processing prior to usual cognitive deficits. Benefits from current interventions targeting communication difficulties in MCI are limited. Yet, neuroplasticity associated with musical experience has been implicated in improving neural representations of speech and offsetting age-related declines in perception. Here, we asked whether these experience-dependent effects of musicianship might extend to aberrant aging and offer some degree of cognitive protection against MCI. During a vowel categorization task, we recorded single-channel EEGs in older adults with putative MCI to evaluate speech encoding across subcortical and cortical levels of the auditory system. Critically, listeners varied in their duration of formal musical training experience (0-21 years). Older musicians exhibited sharpened temporal precision in auditory cortical responses suggesting musical experience produces more efficient processing of acoustic features by offsetting age-related neural delays. Additionally, we found robustness of brainstem responses predicted severity of cognitive decline suggesting early speech representations are sensitive to pre-clinical stages of cognitive impairment. Our preliminary results extend prior studies by demonstrating positive benefits of musical experience in older adults with emergent cognitive impairments.
The ß-catenin-target Fascin-1, altering hepatocyte differentiation, is a new marker of immature cells in hepatoblastomas
Authors: Gest Caroline , Sena Sandra , Neaud Véronique , Loesch Robin , Dugot-Senant Nathalie , Paysan Lisa , Piquet Léo , Robbe Terezinha , Allain Nathalie , Dembele Doulaye , Guettier Catherine , Bioulac-Sage Paulette , Bail Brigitte Le , Grosset Christophe F. , Saltel Frédéric , Lagrée Valérie , Colnot Sabine , Moreau Violaine 
Published: April 2021

ABSTRACTBACKGROUND & AIMSß-catenin is a well-known effector of the Wnt pathway and a key player in cadherin-mediated cell adhesion. Oncogenic mutations of ß-catenin are highly frequent in pediatric liver primary tumors. Those mutations are mostly heterozygous allowing the co-expression of wild-type (WT) and mutated ß-catenins in tumor cells. We investigated the interplay between WT and mutated ß-catenins in liver tumor cells, and searched for new actors of the ß-catenin pathway.METHODSUsing an RNAi strategy in ß-catenin-mutated hepatoblastoma (HB) cells, we dissociated the structural and transcriptional activities of β-catenin, carried mainly by, respectively, WT and mutated proteins. Their impact was characterized using transcriptomic and functional analyses. We studied mice that develop liver tumors upon activation of ß-catenin in hepatocytes (APCKOand ß-cateninΔexon3mice). We made use of transcriptomic data from mouse and human HB specimens and analyzed samples by immunohistochemistry.RESULTSWe highlighted an antagonist role of WT and mutated ß-catenins on hepatocyte differentiation as attested by alteration of hepatocyte markers expression and bile canaliculi formation. We characterized Fascin-1 as a target of ß-catenin involved in hepatocyte differentiation. Using mouse models that allow the formation of two phenotypically distinct tumors (differentiated or undifferentiated), we found that Fascin-1 expression is higher in undifferentiated tumors. Finally, we found that Fascin-1 is a specific marker of the embryonal component in human HBs.CONCLUSIONSIn mice and human, Fascin-1 expression is linked to loss of differentiation and polarity of hepatocytes. Thus, we highlighted Fascin-1 as a new player in the modulation of hepatocyte differentiation associated to ß-catenin pathway alteration in the liver.Data Transparency Statementstudy materials will be made available to other researchers upon request.
Cas9-mediated gene disruption in tetraploidGiardia intestinalis
Authors: Horáčková Vendula , Voleman Luboš , Hagen Kari D. , Petrů Markéta , Vinopalová Martina , Weisz Filip , Janowicz Natalia , Marková Lenka , Motyčková Alžběta , Tůmová Pavla , Dawson Scott C. , Doležal Pavel 
Published: April 2021

ABSTRACTCRISPR/Cas9 system is an extremely powerful technique that is extensively used for various genome modifications in different organisms including parasitic protists.Giardia intestinalis, a protist parasite infecting about 280 million people around the world each year, has been eluding the routine use of CRISPR/Cas9 for generating knock-out cell lines due to the presence of four copies of each gene in its two nuclei. Apart from single exception employing rather laborious Cre/loxP system, no full knock-out cell line has been established yet. In this work, we show the ability ofin-vitroassembled CRISPR/Cas9 components to successfully edit the genome ofG. intestinalis. We further established a cell line stably expressing Cas9 in bothG. intestinalisnuclei. Subsequent introduction of a template for homologous recombination containing the transcription units for the resistance marker and gRNA resulted in the removal of all gene copies at once for three independent experimental genes,mem, cwp1andmlf1. The method was also applicable for the incomplete disruption of an essential gene, as documented by markedly decreased expression oftom40. Finally, testing the efficiency of Cas9-induced recombination revealed that homologous arms as short as 150 bp can be sufficient to establish a full knock-out cell line inG. intestinalis.
Evolution under low antibiotic concentrations: a risk for the selection ofPseudomonas aeruginosamultidrug resistant mutants in nature
Authors: Sanz-García Fernando , Hernando-Amado Sara , Martínez José Luis 
Published: April 2021

ABSTRACTBACKGROUNDAntibiotic pollution of non-clinical environments might have a relevant impact on human health if resistant pathogens are selected. However, this potential risk is often overlooked, since drug concentrations in nature are usually below their minimal inhibitory concentrations (MICs). Albeit, antibiotic resistant bacteria can be selected even at sub-MIC concentrations, in a range that is dubbed the sub-MIC selective window, which depends on both the antibiotic and the pathogen.OBJECTIVESDetermine the sub-MIC selective windows of seven antibiotics of clinical relevance in the opportunistic pathogenPseudomonas aeruginosaand evaluate the risk for selecting resistant mutants in nature, based on published data about the amount of antimicrobials detected in natural environments.METHODSWe conducted evolution experiments ofP. aeruginosaPA14 in presence of sub-MIC concentrations of ceftazidime, amikacin, levofloxacin, ciprofloxacin, tetracycline, polymyxin B or imipenem, and measured drug susceptibility of the evolved populations.RESULTSSub-MIC selective window of quinolones was the largest, and the ones of polymyxin B and imipenem, the narrowest. Clinically relevant multidrug resistant (MDR) mutants (presenting MICs above EUCAST clinical breakpoints) arose within the sub-MIC selective windows of the majority of antibiotics tested, being these phenotypes probably mediated by efflux pumps′ activity.DISCUSSIONOur data show that the concentration of antibiotics reported in aquatic ecosystems -colonizable byP. aeruginosa- are, in occasions, higher than the ones able to select MDR mutants. This finding has implications for understanding the role of different ecosystems and conditions in the emergence of antibiotic resistance from a One-Health point of view. Further, it highlights the importance of delineating the sub-MIC selective windows for drugs of clinical value in pathogens with environmental niches, in order to evaluate the health risks due to antibiotic pollution of natural ecosystems and ultimately tackle antibiotic resistance.
Climate-induced forest dieback drives compositional change in insect communities that is concentrated amongst rare species
Authors: Sire Lucas , Yáñez Paul Schmidt , Wang Cai , Bézier Annie , Courtial Béatrice , Cours Jérémy , Fontaneto Diego , Larrieu Laurent , Bouget Christophe , Thorn Simon , Müller Jörg , Yu Douglas W. , Monaghan Michael T. , Herniou Elisabeth A. , Lopez-Vaamonde Carlos 
Published: April 2021

AbstractMarked decline in insect species richness, abundance and biomass have recently been quantified in Europe. We metabarcoded 224 Malaise-trap samples to investigate whether drought-induced forest dieback and subsequent salvage logging have an impact on flying insects (ca. 3000 insect species) in silver fir Pyrenean forests. We found no evidence that climate-induced forest dieback impacted species richness of flying insects but revealed compositional turnover patterns consistent with those seen during natural forest succession, given that the key covariates explaining compositional variation were canopy openness versus microhabitat diversity and deadwood amount at local and landscape scales, respectively. Importantly, most change was driven by rare species. In contrast, observed levels of salvage logging did not explain change in species richness or composition. Hence, although forest dieback appears to cause changes in species assemblages mimicking natural forest succession, it also increases the risk of catastrophic loss of rare species through homogenization of environmental conditions.
FMRP DIRECTLY INTERACTS WITH R-LOOP AND SHOWS COMPLEX INTERPLAY WITH THE DHX9 HELICASE
Authors: Chakraborty Arijita , Dutta Arijit , Dettori Leonardo G. , Li Jing , Gonzalez Leticia , Xue Xiaoyu , Hehnly Heidi , Sung Patrick , Bah Alaji , Feng Wenyi 
Published: April 2021

ABSTRACTMutations in, or deficiency of, FMRP is responsible for the Fragile X syndrome (FXS), the most common cause for inherited intellectual disability. FMRP is a nucleocytoplasmic protein, primarily characterized as a translation repressor with poorly understood nuclear function(s). We recently uncovered a genome protective role of FMRP. We reported that FXS patient-derived cells lacking FMRP sustain higher level of DNA double-strand breaks than normal cells, a phenotype further exacerbated by DNA replication stress. The stress-induced DSBs occur at sequences prone to form R-loops, which are co-transcriptional RNA:DNA hybrids that have been associated with genome instability. Concordantly, we showed that FXS cells accumulate R-loops under replication stress. Moreover, expression of FMRP and not a mutant deficient in binding nucleic acids and known to cause FXS, FMRPI304N, reduced R-loop-associated DSBs. These observations demonstrated that FMRP promotes genome integrity by preventing R-loop accumulation and chromosome breakage. Here, we explore the mechanism through which FMRP prevents R-loop accumulation in an isogenically controlled CRISPR KO ofFMR1(gene encoding for FMRP) in HEK293T cells. We demonstrate for the first time that FMRP directly binds R-loops. We show that FMRP interacts with DHX9, an RNA helicase that unwinds both double strand RNA and RNA:DNA hybrids and regulates R-loop formation through modulating these activities. This interaction is reduced with FMRPI304N, suggesting that FMRP regulation of R-loop is mediated through DHX9. Interestingly, we show that FMRP inhibits DHX9 helicase activity on RNA:DNA hybrids. Moreover, DHX9 binds chromatin containing R-loops more efficiently in the absence of a functional FMRP. These results suggest an antagonistic relationship between FMRP and DHX9 at the chromatin, where FMRP prevents R-loop formation by suppressing DHX9. Our study sheds new light on our understanding of the genome functions of FMRP.