bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Vagus and Glossopharyngeal Nerves in Two Autonomic Disorders
Authors: Norcliffe-Kaufmann Lucy 
Published: November 2019

Summary:
The glossopharyngeal and vagus cranial nerves provide the brainstem with sensory inputs from different receptors in the heart, lung, and vasculature. This afferent information is critical for the short-term regulation of arterial blood pressure and the buffering of emotional and physical stressors. Glossopharyngeal afferents supply the medulla with continuous mechanoreceptive signals from baroreceptors at the carotid sinus. Vagal afferents ascending from the heart supply mechanoreceptive signals from baroreceptors in different reflexogenic areas including the aortic arch, atria, ventricles, and pulmonary arteries. Ultimately, afferent information from each of these distinct pressure/volume baroreceptors is all relayed to the nucleus tractus solitarius, integrated within the medulla, and used to rapidly adjust sympathetic and parasympathetic activity back to the periphery. Lesions that selectively destroy the afferent fibers of the vagus and/or glossopharyngeal nerves can interrupt the transmission of baroreceptor signaling, leading to extreme blood pressure fluctuations. Vagal efferent neurons project back to the heart to provide parasympathetic cholinergic inputs. When activated, they trigger profound bradycardia, reduce myocardial oxygen demands, and inhibit acute inflammation. Impairment of the efferent vagal fibers seems to play a role in stress-induced neurogenic heart disease (i.e., takotsubo cardiomyopathy). This focused review describes: (1) the importance of the vagus and glossopharyngeal afferent neurons in regulating arterial blood pressure and heart rate, (2) how best to assess afferent and efferent cardiac vagal function in the laboratory, and (3) two clinical phenotypes that arise when the vagal and/or glossopharyngeal nerves do not survive development or are functionally impaired.
How the past impacts the future: modelling the performance of evolutionarily distinct mammals through time
Authors: Bennett D. J. , Sutton M. D. , Turvey S. T. 
Published: November 2019

How does past evolutionary performance impact future evolutionary performance? This is an important question not just for macroevolutionary biologists who wish to chart the phenomena that describe deep-time changes in biodiversity but also for conservation biologists, as evolutionarily distinct species—which may be deemed ‘low-performing’ in our current era—are increasingly the focus of conservation efforts. Contrasting hypotheses exist to account for the history and future of evolutionarily distinct species: on the one hand, they may be relicts of large radiations, potentially ‘doomed’ to extinction; or they may be slow-evolving, ‘living fossils’, likely neither to speciate nor go extinct; or they may be seeds of future radiations. Here, we attempt to test these hypotheses in Mammalia by combining a molecular phylogenetic supertree with fossil record occurrences and measuring change in evolutionary distinctness (ED) at different time slices. With these time slices, we modelled future ED as a function of past ED. We find that past evolutionary performance does indeed have an impact on future evolutionary performance: the most evolutionarily isolated clades tend to become more evolutionarily distinct with time, indicating that low-performing clades tend to remain low-performing throughout their evolutionary history.This article is part of a discussion meeting issue ‘The past is a foreign country: how much can the fossil record actually inform conservation?’
All is flux: the predictive power of fluctuating Quaternary mammalian faunal-climate scenarios
Authors: Schreve Danielle 
Published: November 2019

The long-term impact of Middle and Late Pleistocene glacial-interglacial change led to the major reorganization of mammalian faunal communities in northern Europe through species origination, extinction, evolutionary change and distributional shifts. A Bray–Curtis cluster analysis with single linkage to examine relative faunal similarity was performed on mammalian assemblages from five successively older interglacials (MIS 1, 5e, 7c-a, 9 and 11) in Britain, a region with an exceptionally well-resolved faunal record for this time period. The results indicate a degree of continuity in terms of common interglacial elements occurring across all periods but also reveal that the particular climatic and environmental parameters of each interglacial resulted in the generation of very different faunal assemblages, depending on the length, intensity and structure of the interglacial. Of particular note are the comparability of the mammalian assemblages from warm interglacials MIS 5e and 9, and the high species diversity seen in MIS 7c-a, linked to relatively cool temperate conditions and the spread of dry grasslands. Together, these results offer insight into the overall ‘predictability' of Quaternary mammalian interglacial community composition and what might be expected in the natural evolution of a Holocene interglacial freed of anthropogenic interference.This article is part of a discussion meeting issue ‘The past is a foreign country: how much can the fossil record actually inform conservation?’
Conservation evidence from climate-related stressors in the deep-time marine fossil record
Authors: Clapham Matthew E. 
Published: November 2019

Conservation of marine species requires the ability to predict the effects of climate-related stressors in an uncertain future. Experiments and observations in modern settings provide crucial information, but lack temporal scale and cannot anticipate emergent effects during ongoing global change. By contrast, the deep-time fossil record contains the long-term perspective at multiple global change events that can be used, at a broad scale, to test hypothesized effects of climate-related stressors. For example, geologically rapid carbon cycle disruption has often caused crises in reef ecosystems, and selective extinctions support the hypothesis that greater activity levels promote survival. Geographical patterns of extinction and extirpation were more variable than predicted from modern physiology, with tropical and temperate extinction peaks observed at different ancient events. Like any data source, the deep-time record has limitations but also provides opportunities that complement the limitations of modern and historical data. In particular, the deep-time record is the best source of information on actual outcomes of climate-related stressors in natural settings and over evolutionary timescales. Closer integration of modern and deep-time evidence can expand the types of hypotheses testable with the fossil record, yielding better predictions of extinction risk as climate-related stressors continue to intensify in future oceans.
This article is part of a discussion meeting issue ‘The past is a foreign country: how much can the fossil record actually inform conservation?’
Conservation palaeobiology and the shape of things to come
Authors: Dietl Gregory P. 
Published: November 2019

Conservation decision-making is a forward-looking process that involves choices among alternative images of how the future will unfold. Scenarios, easily understood as stories about plausible futures, are emerging as a powerful approach used by the conservation community to define a range of socio-ecological futures when standard, predictive modelling approaches to decision-making are inappropriate, providing a framework for making robust decisions under uncertainties. Conservation palaeobiologists can help the conservation community imagine the future. The utility of the past centres on orienting us to the present—grounding the future in the realm of what is plausible—by providing context against which to think about future scenarios, which may help stakeholders and decision-makers to develop a new mental map of a conservation problem, inspiring our intentions and moving us purposefully toward a desirable tomorrow.
This article is part of a discussion meeting issue ‘The past is a foreign country: how much can the fossil record actually inform conservation?’
Identification ofde novomutations in prenatal neurodevelopment-associated genes in schizophrenia in two Han Chinese patient-sibling family-based cohorts
Authors: Jiang Shan , Zhou Daizhan , Wang Yin-Ying , Jia Peilin , Wan Chunling , Li Xingwang , He Guang , Cao Dongmei , Jiang Xiaoqian , Kendler Kenneth S. , Tsuang Ming , Mize Travis , Wu Jain-Shing , Lu Yimei , He Lin , Chen Jingchun , Zhao Zhongming , Chen Xiangning 
Published: November 2019

AbstractSchizophrenia (SCZ) is a severe psychiatric disorder with a strong genetic component. High heritability of SCZ suggests a major role for transmitted genetic variants. Furthermore, SCZ is also associated with a marked reduction in fecundity, leading to the hypothesis that alleles with large effects on risk might often occur de novo. In this study, we conducted whole-genome sequencing for 23 families from two cohorts with matched unaffected siblings and parents. Two nonsensede novomutations (DNMs) inGJC1andHIST1H2ADwere identified in SCZ patients. Ten genes (DPYSL2, NBPF1, SDK1, ZNF595, ZNF718, GCNT2, SNX9, AACS, KCNQ1andMSI2) were found to carry more DNMs in SCZ patients than their unaffected siblings by burden test. Expression analyses indicated that these DNM implicated genes showed significantly higher expression in prefrontal cortex in prenatal stage. The DNM in theGJC1gene is highly likely a loss function mutation (pLI = 0.94), leading to the dysregulation of ion channel in the glutamatergic excitatory neurons. Analysis of rare variants in independent exome sequencing dataset indicates thatGJC1has significantly more rare variants in SCZ patients than in unaffected controls. Data from genome-wide association studies suggested that common variants in theGJC1gene may be associated with SCZ and SCZ-related traits. Genes co-expressed withGJC1are involved in SCZ, SCZ-associated pathways and drug targets. These evidence suggest thatGJC1may be a risk gene for SCZ and its function may be involved in prenatal and early neurodevelopment, a vulnerable period for developmental disorders such as SCZ.
HIV-1 Rev interacts with HERV-K RcREs present in the human genome and promotes export of unspliced HERV-K proviral RNA
Authors: Gray Laurie R. , Jackson Rachel E. , Jackson Patrick E. H. , Bekiranov Stefan , Rekosh David , Hammarskjöld Marie-Louise 
Published: November 2019

AbstractBackgroundThe HERV-K (HML-2) viruses are the youngest of the human endogenous retroviruses. They are present as several almost complete proviral copies and numerous fragments in the human genome. Many HERV-K proviruses express a regulatory protein Rec, which binds to an element present in HERV-K mRNAs called the RcRE. This interaction is necessary for the nucleo-cytoplasmic export and expression of HERV-K mRNAs that retain introns and plays a role analogous to that of Rev and the RRE in HIV replication. There are over 900 HERV-K RcREs distributed throughout the human genome. Thus, it was of interest to determine if Rev could functionally interact with selected RcRE elements that map either to HERV-K proviruses or human gene regions. This interaction would have the potential to alter the expression of both HERV-K mRNAs and cellular mRNAs during HIV-1 infection.ResultsIn this study we employed a combination of RNAseq, bioinformatics and cell-based functional assays. Potential RcREs were identified through a number of bioinformatic approaches. They were then tested for their ability to promote export and translation of a reporter mRNA with a retained intron in conjunction with Rev or Rec. Some of the selected elements functioned well with either Rev, Rec or both, whereas some showed little or no function. Rev function on individual RcREs varied and was also dependent on the Rev sequence. We also performed RNAseq on total and cytoplasmic RNA isolated from SupT1 cells expressing HIV Rev, with or without Tat, or HERV-K Rec. Proviral mRNA from three HERV-K loci (4p16.1b, 22q11.23 and most significantly 3q12.3) accumulated in the cytoplasm in the presence of Rev or Tat and Rev, but not Rec. Consistent with this, the 3’ RcRE from 3q12.3 functioned well with HIV-Rev in our reporter assay. In contrast, this RcRE showed little or no function with Rec.ConclusionsThe HIV Rev protein can functionally interact with many RcREs present in the human genome, depending on the RcRE sequence, as well as the Rev sequence. This leads to export of some of the HERV-K proviral mRNAs and also has the potential to change the expression of non-viral genes.
ATP Binding Cassette Proteins ABCG37 and ABCG33 are required for potassium-independent cesium uptake in Arabidopsis roots
Authors: Ashraf Mohammad Arif , Kumagai Sayaka , Ito Keita , Sugita Ryohei , Tanoi Keitaro , Rahman Abidur 
Published: November 2019

AbstractRadiocesium, accumulated in the soil by nuclear accidents is a major environmental concern. The transport process of cesium (Cs+) is tightly linked to the indispensable plant nutrient potassium (K+) as they both belong to the group I alkali metal with similar chemical properties. Most of the transporters that had been characterized to date as Cs+ transporters are directly or indirectly linked to K+. Using a combinatorial approach of physiology, genetics, cell biology and root uptake assay, here we identified two ATP-Binding Cassette (ABC) proteins, ABCG37 and ABCG33 as facilitators of Cs+ influx. The gain-of-function mutant of ABCG37 (abcg37-1) showed hypersensitive response to Cs+-induced root growth inhibition, while the double knock out mutant of ABCG33 and ABCG37 (abcg33-1abcg37-2) showed resistance. Single loss-of-function mutant of ABCG33 and ABCG37 did not show any alteration in Cs+ response. Short term uptake experiment with radioactive Cs+ revealed reduced Cs+ uptake in abcg33-1abgc37-2 compared with wild type in presence or absence of K+. Potassium response and content were unaffected in the double mutant background confirming that Cs+ uptake by ABCG33 and ABCG37 is independent of K+. Collectively, this work identified two ABC proteins as new Cs+ influx carriers, which act redundantly and independent of K+ uptake pathway.
Septal GABAergic Inputs to CA1 Govern Contextual Memory Retrieval
Authors: Sans-Dublanc Arnau , Razzauti Adrià , Desikan Srinidhi , Pascual Marta , de la Rocha Jaime , Monyer Hannah , Sindreu Carlos 
Published: November 2019

AbstractWhether projections from the medial septum regulate the function of the CA1 hippocampus in episodic memory retrieval is not known. Here we show that septal GABAergic inputs to CA1 promote contextual fear memory, blocking the activation of parvalbumin-rich interneurons to facilitate Erk/MAP-kinase signaling in pyramidal cells during retrieval. Thus, suppression of feed-forward inhibition onto CA1 by septal GABAergic neurons gates contextual fear behavior.
Transformation of population code from dLGN to V1 facilitates linear decoding
Authors: Gajic N. Alex Cayco , Durand Séverine , Buice Michael , Iyer Ramakrishnan , Reid Clay , Zylberberg Joel , Shea-Brown Eric 
Published: November 2019

SummaryHow neural populations represent sensory information, and how that representation is transformed from one brain area to another, are fundamental questions of neuroscience. The dorsolateral geniculate nucleus (dLGN) and primary visual cortex (V1) represent two distinct stages of early visual processing. Classic sparse coding theories propose that V1 neurons represent local features of images. More recent theories have argued that the visual pathway transforms visual representations to become increasingly linearly separable. To test these ideas, we simultaneously recorded the spiking activity of mouse dLGN and V1 in vivo. We find strong evidence for both sparse coding and linear separability theories. Surprisingly, the correlations between neurons in V1 (but not dLGN) were shaped as to be irrelevant for stimulus decoding, a feature which we show enables linear separability. Therefore, our results suggest that the dLGN-V1 transformation reshapes correlated variability in a manner that facilitates linear decoding while producing a sparse code.
Prefrontal deep projection neurons enable cognitive flexibility via persistent feedback monitoring
Authors: Timothy Spellman , Malka Svei , Jesse Kaminsky , Gabriela Manzano-Nieves , Conor Liston 
Published: November 2019

SummaryCognitive flexibility, the ability to alter one’s strategy according to changing stimulus-response-reward relationships, is critical for acquiring and updating learned behavior. Attentional set-shifting, a test of cognitive flexibility, depends on the activity of prefrontal cortex (PFC). It remains unclear, however, what specific role PFC neurons play and how they interact to support set-shifting. One widely held view is that prefrontal activity biases sensorimotor responses by mediating attention. Using optogenetics and 2-photon calcium imaging, we demonstrate that, while PFC activity does encode attentional sets, this activity does not bias sensorimotor responses. Rather, PFC activity enables set-shifting by encoding trial feedback information, a role it has been known to play in other contexts. We identify a circuit-level mechanism that supports feedback monitoring through persistent, recurring activity bridging multiple trials. Unexpectedly, the functional properties of PFC cells did not vary with their efferent projection targets in this context. Instead, representations of trial feedback formed a topological gradient, with cells more strongly selective for feedback information located further from the pial surface and receiving denser afferent inputs from the anterior cingulate cortex. Together, these findings identify a critical role for deep PFC projection neurons in enabling set-shifting through behavioral feedback monitoring.
Early Treatment Response in First Episode Psychosis: A 7-Tesla Magnetic Resonance Spectroscopic Study of Glutathione and Glutamate
Authors: Dempster Kara , Jeon Peter , MacKinley Michael , Williamson Peter , Théberge Jean , Palaniyappan Lena 
Published: November 2019

AbstractEarly response to antipsychotic medications is one of the most important determinants of later symptomatic and functional outcomes in psychosis. Glutathione and glutamate have emerged as promising therapeutic targets for patients demonstrating inadequate response to dopamine-blocking antipsychotics. Nevertheless, the role of these neurochemicals in the mechanism of early antipsychotic response remains poorly understood. Using a longitudinal design and ultra-high field 7-Tesla magnetic resonance spectroscopy (MRS) protocol in 53 subjects, we report the association between dorsal anterior cingulate cortex glutamate and glutathione, with time to treatment response in drug-naïve (34.6% of the sample) or minimally medicated first episode patients with non-affective psychosis. Time to response was defined as the number of weeks required to reach a 50% reduction in the PANSS-8 scores. Higher glutathione was associated with shorter time to response (F=4.86,P= .017), while higher glutamate was associated with more severe functional impairment (F=5.33,P= .008). There were no significant differences between patients and controls on measures of glutamate or glutathione. For the first time, we have demonstrated an association between higher glutathione and favourable prognosis in FEP. We propose that interventions that increase brain glutathione levels may improve outcomes of early intervention in psychosis.
Differential effects of ethanol on behavior and GABAAreceptor subunit expression in zebrafish (Danio rerio) with alternative stress coping styles
Authors: Goodman Alexander C. , Wong Ryan Y. 
Published: November 2019

AbstractVariation in stress responses between individuals is linked to factors ranging from stress coping styles to sensitivity of neurotransmitter systems. Many anxiolytic compounds (e.g. ethanol) can increase stressor engagement through modulation of neurotransmitter systems and are used to investigate stress response mechanisms. Here we assessed the role of the GABAAsystem on the variation of the behavioral stress response by comparing individuals differing in stress coping styles that were chronically treated with ethanol. Specifically, we investigated resulting changes in stress-related behavior and whole-brain GABAAreceptor subunits (gabra1, gabra2, gabrd, &gabrg2) in response to a novelty stressor. There were significant main and interaction effects on two stress-related behaviors, where the ethanol-treated proactive individuals showed lower stress-related behaviors than their reactive counterparts. Proactive individuals showed significantly higher expression ofgabra1, gabra2, andgabrg2compared to reactive individuals and ethanol treatment resulted in upregulation ofgabra1andgabrg2in both stress coping styles. These results show that differences in stress-related behaviors between stress coping styles may be facilitated in part by expression of select GABAAreceptor subunits.
MS2-TRIBE evaluates protein-RNA interactions and nuclear organization of transcription by RNA editing
Authors: Biswas Jeetayu , Rahman Reazur , Gupta Varun , Rosbash Michael , Singer Robert H. 
Published: November 2019

AbstractNearly every step of RNA regulation is mediated by binding proteins (RBPs). The most common method to identify specific RBP target transcripts in vivo is by crosslinking (“CLIP” and its variants), which rely on protein-RNA crosslinking and specific antibodies. Another recently introduced method exploits RNA editing, with the catalytic domain of ADAR covalently attached to a specific RBP (“TRIBE”). Both approaches suffer from difficulties in distinguishing real RNA targets from false negative and especially false positive signals. To critically evaluate this problem, we used fibroblasts from a mouse where every endogenous β-actin mRNA molecule was tagged with the bacteriophage MS2 RNA stem loops; hence there is only a single bona fide target mRNA for the MS2 capsid protein (MCP). CLIP and TRIBE could both detect the single RNA target, albeit with some false positives (transcripts lacking the MS2 stem loops). Consistent false positive CLIP signals could be attributed to nonspecific antibody crosslinking. To our surprise, the supposed false positive TRIBE targets correlated with the location of genes spatially proximal to the β-actin gene. This result indicates that MCP-ADAR bound to β-actin mRNA contacted and edited nearby nascent transcripts, as evidenced by frequent intronic editing. Importantly, nascent transcripts on nearby chromosomes were also edited, agreeing with the interchromosomal contacts observed in chromosome paint and Hi-C. The identification of nascent RNA-RNA contacts imply that RNA-regulatory proteins such as splicing factors can associate with multiple nascent transcripts and thereby form domains of post-transcriptional activity, which increase their local concentrations. These results more generally indicate that TRIBE combined with the MS2 system, MS2-TRIBE, is a new tool to study nuclear RNA organization and regulation.