bluuebunny/crossref_metadata_2025 huggingface dataset:
Impairments in Hippocampal Place Cell Sequences during Errors in Spatial Memory
Authors: Zheng Chenguang , Hwaun Ernie , Colgin Laura Lee
Published: April 2020

Theta and gamma rhythms temporally coordinate sequences of hippocampal place cell ensembles during active behaviors, while sharp wave-ripples coordinate place cell sequences during rest. We used a delayed match-to-place memory task to investigate whether such coordination of hippocampal place cell sequences is disrupted when memory errors occur. As rats approached a learned reward location, place cell sequences represented paths extending toward the reward location during correct trials. During error trials, paths coded by place cell sequences were significantly shorter as rats approached incorrect stop locations, with place cell sequences starting at a significantly delayed phase of the theta cycle. During rest, place cell sequences replayed representations of paths that were highly likely to end at the correct reward location during correct but not error trials. The relationship between place cell sequences and gamma rhythms, however, did not differ between correct and error trials. These results suggest that coordination of place cell sequences by theta rhythms and sharp wave-ripples is important for successful spatial memory.
Reactive Oxygen Species Modulate Activity-Dependent AMPA Receptor Transport inC. elegans
Authors: Doser Rachel L. , Amberg Gregory C. , Hoerndli Frederic J.
Published: April 2020

The AMPA subtype of synaptic glutamate receptors (AMPARs) play an essential role in cognition. Their function, numbers and change at synapses during synaptic plasticity, is tightly regulated by neuronal activity. Although we know that long-distance transport of AMPARs is essential for this regulation, we don’t understand the regulatory mechanisms of it. Neuronal transmission is a metabolically demanding process in which ATP consumption and production are tightly coupled and regulated. Aerobic ATP synthesis unavoidably produces reactive oxygen species (ROS), such as hydrogen peroxide, which are known modulators of calcium signaling. Although a role for calcium signaling in AMPAR transport has been described, there is little understanding of the mechanisms involved and no known link to physiological ROS signaling. Here, using real-timein vivoimaging of AMPAR transport in the intactC. elegansnervous system, we demonstrate that long-distance synaptic AMPAR transport is bidirectionally regulated by calcium influx and activation of calcium/calmodulin-dependent protein kinase II. Quantifyingin vivocalcium dynamics revealed that modest, physiological increases in ROS decrease calcium transients inC. elegansglutamatergic neurons. By combining genetic and pharmacological manipulation of ROS levels and calcium influx, we reveal a mechanism in which physiological increases in ROS cause a decrease in synaptic AMPAR transport and delivery by modulating activity-dependent calcium signaling. Taken together, our results identify a novel role for oxidant signaling in the regulation of synaptic AMPAR transport and delivery, which in turn could be critical for coupling the metabolic demands of neuronal activity with excitatory neurotransmission.

SIGNIFICANCE AND IMPACT

Synaptic AMPARs are critical for excitatory synaptic transmission. The disruption of their synaptic localization and numbers is associated with numerous psychiatric, neurological, and neurodegenerative conditions. However, very little is known about the regulatory mechanisms controlling transport and delivery of AMPAR to synapses. Here, we describe a novel physiological signaling mechanism in which ROS, such as hydrogen peroxide, modulate AMPAR transport by modifying activity-dependent calcium influx. Our findings provide the first evidence in support of a mechanistic link between physiological ROS signaling, AMPAR transport, localization, and excitatory transmission. Of potential therapeutic importance, dysregulation of intracellular calcium and ROS signaling is implicated in the pathogenesis of several neurodegenerative disorders including Alzheimer’s and Parkinson’s disease.
iPSC-derived hepatocytes from patients with nonalcoholic fatty liver disease display a disease-specific gene expression profile
Authors: Duwaerts Caroline C. , Her Chris L. , Phillips Nathaniel J. , Willenbring Holger , Mattis Aras N. , Maher Jacquelyn J.
Published: April 2020

Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of liver disease worldwide.1 Animal models are widely used to investigate the mechanisms of fatty liver disease, but they do not faithfully represent NAFLD in humans.2 Thus, there is strong interest in studying NAFLD pathogenesis directly in humans whenever possible. One strategy that is gaining momentum is to utilize iPSC-derived hepatocytes from individual human subjects in complex cell/organ platforms with the goal of reproducing a NAFLD-like state in vitro.3-6 Our group has taken a different approach, positing that iPSC-Heps from a population of NAFLD patients would provide independent insight into the human disease. In this study we generated iPSCs and iPSC-Heps from a well-defined cohort of NAFLD patients. Our objective was to determine whether as a group, in the absence of any metabolic challenge, they exhibit common disease-specific signatures that are distinct from healthy controls.
Repeatability and reproducibility assessment in a large-scale population-based microbiota study: case study on human milk microbiota
Authors: Moossavi Shirin , Fehr Kelsey , Moraes Theo J. , Khafipour Ehsan , Azad Meghan B.
Published: April 2020

Background

Quality control including assessment of batch variabilities and confirmation of repeatability and reproducibility are integral component of high throughput omics studies including microbiome research. Batch effects can mask true biological results and/or result in irreproducible conclusions and interpretations. Low biomass samples in microbiome research are prone to reagent contamination; yet, quality control procedures for low biomass samples in large-scale microbiome studies are not well established.

Results

In this study we have proposed a framework for an in-depth step-by-step approach to address this gap. The framework consists of three independent stages: 1) verification of sequencing accuracy by assessing technical repeatability and reproducibility of the results using mock communities and biological controls; 2) contaminant removal and batch variability correction by applying a two-tier strategy using statistical algorithms (e.g.decontam) followed by comparison of the data structure between batches; and 3) corroborating the repeatability and reproducibility of microbiome composition and downstream statistical analysis. Using this approach on the milk microbiota data from the CHILD Cohort generated in two batches (extracted and sequenced in 2016 and 2019), we were able to identify potential reagent contaminants that were missed with standard algorithms, and substantially reduce contaminant-induced batch variability. Additionally, we confirmed the repeatability and reproducibility of our reslults in each batch before merging them for downstream analysis.

Conclusion

This study provides important insight to advance quality control efforts in low biomass microbiome research. Within-study quality control that takes advantage of the data structure (i.e.differential prevalence of contaminants between batches) would enhance the overall reliability and reproducibility of research in this field.
Disease-associated mutations in TRPM3 render the channel overactive via two distinct mechanisms
Authors: Zhao Siyuan , Yudin Yevgen , Rohacs Tibor
Published: April 2020

Transient Receptor Potential Melastatin 3 (TRPM3) is a Ca2+permeable non-selective cation channel activated by heat and chemical agonists such as pregnenolone sulfate and CIM0216. TRPM3 mutations in humans were recently reported to be associated with intellectual disability and epilepsy; the functional effects of those mutations however were not reported. Here we show that both disease-associated mutations of TRPM3 render the channel overactive, but likely via different mechanisms. The Val to Met substitution in the S4-S5 loop induced a larger increase in basal activity and agonist sensitivity at room temperature than the Pro to Gln substitution in the extracellular segment of S6. In contrast, heat activation was increased more by the S6 mutant than by the S4-S5 segment mutant. Both mutants were inhibited by the TRPM3 antagonist primidone, suggesting a potential therapeutic intervention to treat this disease.
Recovery and Community Succession of theZostera marinaRhizobiome After Transplantation
Authors: Wang Lu , English Mary K. , Tomas Fiona , Mueller Ryan S.
Published: April 2020

Seagrasses can form mutualisms with their microbiomes that facilitate the exchange of energy sources, nutrients, and hormones, and ultimately impact plant stress resistance. Little is known about community succession within the belowground seagrass microbiome after disturbance and its potential role in the plant’s recovery after transplantation. We transplantedZostera marinashoots with and without an intact rhizosphere and cultivated plants for four weeks while characterizing microbiome recovery and effects on plant traits. Rhizosphere and root microbiomes were compositionally distinct, likely representing discrete microbial niches. Furthermore, microbiomes of washed transplants were initially different from those of sod transplants, and recovered to resemble an undisturbed state within fourteen days. Conspicuously, changes in microbial communities of washed transplants corresponded with changes in rhizosphere sediment mass and root biomass, highlighting the strength and responsive nature of the relationship between plants, their microbiome, and the environment. Potential mutualistic microbes that were enriched over time include those that function in the cycling and turnover of sulfur, nitrogen, and plant-derived carbon in the rhizosphere environment. These findings highlight the importance and resiliency of the seagrass microbiome after disturbance. Consideration of the microbiome will have meaningful implications on habitat restoration practices.

Importance

Seagrasses are important coastal species that are declining globally, and transplantation can be used to combat these declines. However, the bacterial communities associated with seagrass rhizospheres and roots (the microbiome) are often disturbed or removed completely prior to transplantation. The seagrass microbiome benefits seagrasses through metabolite, nutrient, and phytohormone exchange, and contributes to the ecosystem services of seagrass meadows by cycling sulfur, nitrogen, and carbon. This experiment aimed to characterize the importance and resilience of the seagrass belowground microbiome by transplantingZostera marinawith and without intact rhizospheres and tracking microbiome and plant morphological recovery over four weeks. We found the seagrass microbiome to be resilient to transplantation disturbance, recovering after fourteen days. Additionally, microbiome recovery was linked with seagrass morphology, coinciding with increases in rhizosphere sediment mass and root biomass. Results of this study can be used to include microbiome responses in informing future restoration work.
Mendelian randomization analysis revealed causal effects from gut microbiota to abdominal obesity
Authors: Xu Qian , Zhang Shan-Shan , Pei Yu-Fang , Ni Jing-Jing , Zhang Lei , Wang Rui-Rui , Weng Yu-Jing , Cui Xun , Wei Xin-Tong
Published: April 2020

Although recent studies have revealed the association between the gut microbiota and obesity, the causality remains elusive. We performed a Mendelian Randomization (MR) analysis to determine whether there is a causal relationship between gut microbiota and abdominal obesity. We used a two-sample MR approach to assess the causal effect from gut microbiota to obesity based on genome-wide association studies (GWAS) summary statistics. The GWAS summary statistics of gut microbiota obtained from UK-twins cohort (N=1,126) were used as discovery sample exposure, and the GWAS summary statistics from the Genetic Environmental Microbial (GEM) project (N=1,098) were used as replication sample exposure. Trunk fat mass (TFM) summary statistics from the UK Biobank (UKB) cohort (N=330,762) were used as outcome. Bacteria were grouped into taxa features at family level. A total of 16 families were analyzed in the discovery sample. FamilyBarnesiellaceaewas associated with TFM at the nominal significance level (b=-3.81×10−4,P=1.96×10−3). The causal association was successfully replicated in the replication sample (b=-7.34×10−3,P=2.77×10−2). Our findings provided evidence of causal relationship from microbiota to fat development, and may be helpful in selecting potential causal bacteria for manipulating candidate gut microbiota to therapy obesity.

IMPORTANCE

Obesity, as a global public health problem, is one of the most important risk factors contributing to the overall global burden of disease, and is associated with an increased risk of cardiovascular disease, type 2 diabetes, and certain cancers. Recent studies have shown that gut microbiota is closely related to the development of obesity, but the causal relationship is unclear. Therefore, it is necessary to identify the causality between gut microbiota and obesity. The significance of our research is in identifying the causal relationship from specific bacteria to fat development, which will provide the new insights into the microbiota mediated the fat development mechanism.
Gastrointestinal symptoms as Covid-19 onset in hospitalized Italian patients
Authors: Buscarini Elisabetta , Manfredi Guido , Brambilla Gianfranco , Menozzi Fernanda , Londoni Claudio , Alicante Saverio , Iiritano Elena , Romeo Samanta , Pedaci Marianna , Benelli Gianpaolo , Canetta Ciro , Lapiana Giuseppe , Merli Guido , Scartabellati Alessandro , Viganò Giovanni , Sfogliarini Roberto , Melilli Giovanni , Assandri Roberto , Cazzato Daniele , Rossi Davide Sebastiano , Usai Susanna , Tramacere Irene , Pellegata Germano , Lauria Giuseppe
Published: April 2020

Objective

To assess the prevalence of gastrointestinal symptoms and their correlation with need of non-invasive ventilatory support, intensive care unit admission and death in hospitalized SARS-CoV-2 patients.

Design

Since February 21th 2020, all individuals referred to our emergency department for suspected SARS-CoV-2 underwent a standardized assessment of body temperature and pulse oximetry, hematological screening, chest X-ray and/or computed tomography (CT), and SARS-CoV-2 assay on nasopharyngeal swab. Medical history and GI symptoms including nausea, vomit, diarrhea, and abdominal pain were recorded. were recorded.

Results

GI symptoms were the main presentation in 42 (10.2%) of 411 patients, with a mean onset 4.9 +/-… days before admission. In 5 (1.2%) patients GI symptoms have not been associated with respiratory symptoms or fever. We found an inverse trend for ICU admission and death as compared with patients without GI symptoms.

Conclusions

GI symptoms can be an early and not negligible feature of Covid-19, and might be correlated with a more benign disease course.
Characterization and clinical course of 1000 patients with COVID-19 in New York: retrospective case series
Authors: Argenziano Michael G , Bruce Samuel L , Slater Cody L , Tiao Jonathan R , Baldwin Matthew R , Barr R Graham , Chang Bernard P , Chau Katherine H , Choi Justin J , Gavin Nicholas , Goyal Parag , Mills Angela M , Patel Ashmi A , Romney Marie-Laure S , Safford Monika M. , Schluger Neil W , Sengupta Soumitra , Sobieszczyk Magdalena E , Zucker Jason E , Asadourian Paul A , Bell Fletcher M , Boyd Rebekah , Cohen Matthew F , Colquhoun MacAlistair I , Colville Lucy A , de Jonge Joseph H , Dershowitz Lyle B , Dey Shirin A , Eiseman Katherine A , Girvin Zachary P , Goni Daniella T , Harb Amro A , Herzik Nicholas , Householder Sarah , Karaaslan Lara E , Lee Heather , Lieberman Evan , Ling Andrew , Lu Ree , Shou Arthur Y , Sisti Alexander C , Snow Zachary E , Sperring Colin P , Xiong Yuqing , Zhou Henry W , Natarajan Karthik , Hripcsak George , Chen Ruijun
Published: April 2020

Objective

To characterize patients with coronavirus disease 2019 (COVID-19) in a large New York City (NYC) medical center and describe their clinical course across the emergency department (ED), inpatient wards, and intensive care units (ICUs).

Design

Retrospective manual medical record review.

Setting

NewYork-Presbyterian/Columbia University Irving Medical Center (NYP/CUIMC), a quaternary care academic medical center in NYC.

Participants

The first 1000 consecutive patients with laboratory-confirmed COVID-19.

Methods

We identified the first 1000 consecutive patients with a positive RT-SARS-CoV-2 PCR test who first presented to the ED or were hospitalized at NYP/CUIMC between March 1 and April 5, 2020. Patient data was manually abstracted from the electronic medical record.

Main outcome measures

We describe patient characteristics including demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, mortality, and disposition.

Results

Among the first 1000 patients, 150 were ED patients, 614 were admitted without requiring ICU-level care, and 236 were admitted or transferred to the ICU. The most common presenting symptoms were cough (73.2%), fever (72.8%), and dyspnea (63.1%). Hospitalized patients, and ICU patients in particular, most commonly had baseline comorbidities including of hypertension, diabetes, and obesity. ICU patients were older, predominantly male (66.9%), and long lengths of stay (median 23 days; IQR 12 to 32 days); 78.0% developed AKI and 35.2% required dialysis. Notably, for patients who required mechanical ventilation, only 4.4% were first intubated more than 14 days after symptom onset. Time to intubation from symptom onset had a bimodal distribution, with modes at 3-4 and 9 days. As of April 30, 90 patients remained hospitalized and 211 had died in the hospital.

Conclusions

Hospitalized patients with COVID-19 illness at this medical center faced significant morbidity and mortality, with high rates of AKI, dialysis, and a bimodal distribution in time to intubation from symptom onset.
Term Matrix: A novel Gene Ontology annotation quality control system based on ontology term co-annotation patterns
Authors: Wood Valerie , Carbon Seth , Harris Midori A. , Lock Antonia , Engel Stacia R. , Hill David P. , Van Auken Kimberly , Attrill Helen , Feuermann Marc , Gaudet Pascale , Lovering Ruth C. , Poux Sylvain , Rutherford Kim M. , Mungall Christopher J.
Published: April 2020

Biological processes are accomplished by the coordinated action of gene products. Gene products often participate in multiple processes, and can therefore be annotated to multiple Gene Ontology (GO) terms. Nevertheless, processes that are functionally, temporally, and/or spatially distant may have few gene products in common, and co-annotation to unrelated processes likely reflects errors in literature curation, ontology structure, or automated annotation pipelines. We have developed an annotation quality control workflow that uses rules based on mutually exclusive processes to detect annotation errors, based on and validated by case studies including the three we present here: fission yeast protein-coding gene annotations over time; annotations for cohesin complex subunits in human and model species; and annotations using a selected set of GO biological process terms in human and five model species. For each case study, we reviewed available GO annotations, identified pairs of biological processes which are unlikely to be correctly co-annotated to the same gene products (e.g., amino acid metabolism and cytokinesis), and traced erroneous annotations to their sources. To date we have generated 107 quality control rules, and corrected 289 manual annotations in eukaryotes and over 2.5 million automatically propagated annotations across all taxa.
Two decades of suspect evidence for adaptive DNA-sequence evolution – Less negative selection misconstrued as positive selection
Authors: Chen Qipian , He Ziwen , Feng Xiao , Yang Hao , Shi Suhua , Wu Chung-I
Published: April 2020

Evidence for biological adaptation is often obtained by studying DNA sequence evolution. Since the analyses are affected by both positive and negative selection, studies usually assume constant negative selection in the time span of interest. For this reason, hundreds of studies that conclude adaptive evolution might have reported false signals caused by relaxed negative selection. We test this suspicion two ways. First, we analyze the fluctuation in population size, N, during evolution. For example, the evolutionary rate in the primate phylogeny could vary by as much as 2000 fold due to the variation in N alone. Second, we measure the variation in negative selection directly by analyzing the polymorphism data from four taxa (Drosophila, Arabidopsis, primates, and birds, with 64 species in total). The strength of negative selection, as measured by the ratio of nonsynonymous/synonymous polymorphisms, fluctuates strongly and at multiple time scales. The two approaches suggest that the variation in the strength of negative selection may be responsible for the bulk of the reported adaptive genome evolution in the last two decades. This study corroborates the recent report1on the inconsistent patterns of adaptive genome evolution. Finally, we discuss the path forward in detecting adaptive sequence evolution.
Iterative inhibition of commissural growth cone exploration, not post-crossing barrier, ensures forward midline navigation through SlitC-PlxnA1 signaling
Authors: Ducuing Hugo , Gardette Thibault , Pignata Aurora , Kindbeiter Karine , Bozon Muriel , Thoumine Olivier , Delloye-Bourgeois Céline , Tauszig-Delamasure Servane , Castellani Valérie
Published: April 2020

Sensitization to Slits and Semaphorin (Sema)3B floor plate repellents after midline crossing is thought to be the mechanism expelling commissural axons contralaterally and preventing their back-turning. We studied the role of Slit-C terminal fragment sharing with Sema3B the Plexin (Plxn) A1 receptor, newly implicated in midline guidance. We generated a knock-in mouse strain baring PlxnA1Y1815F mutation altering SlitC but not Sema3B responses and observed recrossing phenotypes. Using fluorescent reporters, we found that Slits and Sema3B form clusters decorating an unexpectedly complex mesh of ramified FP glia basal processes spanning the entire navigation path. Time-lapse analyzes revealed that impaired SlitC sensitivity destabilized axon trajectories by inducing high levels of growth cone exploration from the floor plate entry, increasing risk of aberrant decisions. Thus, FP crossing is unlikely driven by post-crossing sensitization to SlitC. Rather, SlitC limits growth cone plasticity and exploration through reiterated contacts, continuously imposing a straight and forward-directed trajectory.
Half of the world’s tree biodiversity is unprotected and is increasingly threatened by human activities
Authors: Guo Wen-Yong , Serra-Diaz Josep M. , Schrodt Franziska , Eiserhardt Wolf L. , Maitner Brian S. , Merow Cory , Violle Cyrille , Anand Madhur , Belluau Michaël , Bruun Hans Henrik , Byun Chaeho , Catford Jane A. , Cerabolini Bruno E. L. , Chacón-Madrigal Eduardo , Ciccarelli Daniela , Cornelissen Johannes H. C. , Dang-Le Anh Tuan , de Frutos Angel , Dias Arildo S. , Giroldo Aelton B. , Guo Kun , Gutiérrez Alvaro G. , Hattingh Wesley , He Tianhua , Hietz Peter , Hough-Snee Nate , Jansen Steven , Kattge Jens , Klein Tamir , Komac Benjamin , Kraft Nathan , Kramer Koen , Lavorel Sandra , Lusk Christopher H. , Martin Adam R. , Mencuccini Maurizio , Michaletz Sean T. , Minden Vanessa , Mori Akira S. , Niinemets Ülo , Onoda Yusuke , Onstein Renske E. , Peñuelas Josep , Pillar Valério D. , Pisek Jan , Robroek Bjorn J.M. , Schamp Brandon , Slot Martjin , Sosinski Ênio , Soudzilovskaia Nadejda A. , Thiffault Nelson , van Bodegom Peter , van der Plas Fons , Wright Ian J. , Xu Wu-Bing , Zheng Jingming , Enquist Brian J. , Svenning Jens-Christian
Published: April 2020

Although trees are key to ecosystem functioning, many forests and tree species across the globe face strong threats. Preserving areas of high biodiversity is a core priority for conservation; however, different dimensions of biodiversity and varied conservation targets make it difficult to respond effectively to this challenge. Here, we (i) identify priority areas for global tree conservation using comprehensive coverage of tree diversity based on taxonomy, phylogeny, and functional traits; and (ii) compare these findings to existing protected areas and global biodiversity conservation frameworks. We find thatca. 51% of the top-priority areas for tree biodiversity are located in current protected areas. The remaining half top-priority areas are subject to moderate to high human pressures, indicating conservation actions are needed to mitigate these human impacts. Our findings emphasize the effectiveness of using tree conservation priority areas for future global conservation planning.
Exploration of natural red-shifted rhodopsins using a machine learning-based Bayesian experimental design
Authors: Inoue Keiichi , Karasuyama Masayuki , Nakamura Ryoko , Konno Masae , Yamada Daichi , Mannen Kentaro , Nagata Takashi , Inatsu Yu , Yura Kei , Béjà Oded , Kandori Hideki , Takeuchi Ichiro
Published: April 2020

Microbial rhodopsins are photoreceptive membrane proteins utilized as molecular tools in optogenetics. In this paper, a machine learning (ML)-based model was constructed to approximate the relationship between amino acid sequences and absorption wavelengths using ~800 rhodopsins with known absorption wavelengths. This ML-based model was specifically designed for screening rhodopsins that are red-shifted from representative rhodopsins in the same subfamily. Among 5,558 candidate rhodopsins suggested by a protein BLAST search of several protein databases, 40 were selected by the ML-based model. The wavelengths of these 40 selected candidates were experimentally investigated, and 32 (80%) showed red-shift gains. In addition, four showed red-shift gains > 20 nm, and two were found to have desirable ion-transporting properties, indicating that they were potentially useful in optogenetics. These findings suggest that an ML-based model can reduce the cost for exploring new functional proteins.
Parallel factor analysis enables quantification and identification of highly-convolved data independent-acquired protein spectra
Authors: Buric Filip , Zrimec Jan , Zelezniak Aleksej
Published: April 2020

High-throughput data-independent acquisition (DIA) is the method of choice for quantitative proteomics, combining the best practices of targeted and shotgun proteomics approaches. The resultant DIA spectra are, however, highly convolved and with no direct precursor-fragment correspondence, complicating the analysis of biological samples. Here we present PARADIAS (PARAllel factor analysis of Data Independent Acquired Spectra), a GPU-powered unsupervised multiway factor analysis framework that deconvolves multispectral scans to individual analyte spectra, chromatographic profiles, and sample abundances, using the PARAFAC tensor decomposition method based on variation of informative spectral features. The deconvolved spectra can be annotated with traditional database search engines or used as a high-quality input forde novosequencing methods. We demonstrate that spectral libraries generated with PARADIAS substantially reduce the false discovery rate underlying the validation of spectral quantification. PARADIAS covers up to 33 times more total ion current than library-based approaches, which typically use less than 5 % of total recorded ions, thus allowing the quantification and identification of signals from unexplored DIA spectra.
Analysis of continuous neuronal activity evoked by natural speech with computational corpus linguistics methods
Authors: Schilling Achim , Tomasello Rosario , Henningsen-Schomers Malte R. , Zankl Alexandra , Surendra Kishore , Haller Martin , Karl Valerie , Uhrig Peter , Maier Andreas , Krauss Patrick
Published: April 2020

In the field of neurobiology of language, neuroimaging studies are generally based on stimulation paradigms consisting of at least two different conditions. Designing those paradigms can be very time-consuming and this traditional approach is necessarily data-limited. In contrast, in computational linguistics analyses are often based on large text corpora, which allow a vast variety of hypotheses to be tested by repeatedly re-evaluating the data set. Furthermore, text corpora also allow exploratory data analysis in order to generate new hypotheses. By drawing on the advantages of both fields, neuroimaging and corpus linguistics, we here present a unified approach combining continuous natural speech and MEG to generate a corpus of speech-evoked neuronal activity.
The early development and physiology ofXenopus laevistadpole lateral line system
Authors: Saccomanno Valentina , Love Heather , Sylvester Amy , Li Wen-Chang
Published: April 2020

Xenopus laevishas a lateral line mechanosensory system throughout its full life cycle. Previous studies of the tadpole lateral line system revealed that it may play a role in escape behaviour. In this study, we used DASPEI staining to reveal the location of tadpole lateral line neuromasts. Destroying these neuromasts with neomycin resulted in loss of escape responses in tadpoles. We then studied the physiology of anterior lateral line in immobilised tadpoles. Activating the neuromasts behind one eye could evoke asymmetrical motor nerve discharges when the tadpole was resting, suggestive of turning/escape, followed by fictive swimming. When the tadpole was already producing fictive swimming however, anterior lateral line activation reliably led to the termination of swimming. The anterior lateral line had spontaneous afferent discharges at rest, and when activated showed typical adaptation. There were also efferent activities during tadpole swimming, the activity of which was loosely in phase with ipsilateral motor nerve discharges, implying modulation by the motor circuit from the same side. Calcium imaging experiments located sensory interneurons in the primary anterior lateral line nucleus in the hindbrain. Future studies are needed to reveal how sensory information is processed by the central circuit to determine tadpole motor behaviour.

Summary statement

Activating tadpole anterior lateral line evokes escape responses followed by swimming and halts ongoing swimming. The afferent and efferent activities and sensory interneuron locations in the hindbrain are reported.
Intrinsic/extrinsic duality of large-scale neural functional integration in the human brain
Authors: Sjøgård Martin , Bourguignon Mathieu , Costers Lars , Dumitrescu Alexandru , Coolen Tim , Roshchupkina Liliia , Destoky Florian , Bertels Julie , Niesen Maxime , Ghinst Marc Vander , van Schependom Jeroen , Nagels Guy , Urbain Charline , Peigneux Philippe , Goldman Serge , Woolrich Mark W. , De Tiège Xavier , Wens Vincent
Published: April 2020

Human brain activity is not merely responsive to environmental context but includes intrinsic dynamics, as suggested by the discovery of functionally meaningful neural networks at rest, i.e., even without explicit engagement of the corresponding function. Yet, the neurophysiological coupling mechanisms distinguishing intrinsic (i.e., task-invariant) from extrinsic (i.e., task-dependent) brain networks remain indeterminate. Here, we investigated functional brain integration using magnetoencephalography throughout rest and various tasks recruiting different functional systems and modulating perceptual/cognitive loads. We demonstrated that two distinct modes of neural communication continually operate in parallel: extrinsic coupling supported by phase synchronization and intrinsic integration encoded in amplitude correlation. Intrinsic integration also contributes to phase synchronization, especially over short (second-long) timescales, through modulatory effects of amplitude correlation. Our study establishes the foundations of a novel conceptual framework for human brain function that fundamentally relies on electrophysiological features of functional integration. This framework blurs the boundary between resting-state and task-related neuroimaging.
Defining Epidermal Stem Cell Fate Infidelity and Immunogenicity in Hidradenitis Suppurativa at the Single-Cell Resolution
Authors: Marohn Meaghan , Lin Meng-ju , Yu Wei-wen , Mendoza Ciara Mae , Remark Juliana , Khodadadi-Jamayran Alireza , Chiu Ernest S. , Lu Catherine Pei-ju
Published: April 2020

Hidradenitis suppurativa (HS) is a severe chronic inflammatory skin disease affecting human apocrine sweat gland-bearing skin regions. One unique feature of HS is the development of keratinized sinus tracts that grow extensively deep in the dermis and are highly immunogenic. Here, we demonstrated that the stem cell fate infidelity exists in the HS sinus tracts, which exhibit features of both surface epidermis and appendages. Using single cell transcriptome analyses, we finely dissected different compartments of the HS epithelium and identified their respective changes in cytokine expression during disease progression and the critical interactions with the immune cells. Together, our work provides advanced understanding of the pathological epidermal remodeling and important implications for HS therapeutics.
White matter microstructure across the adult lifespan: A mixed longitudinal and cross-sectional study using advanced diffusion models and brain-age prediction
Authors: Beck Dani , de Lange Ann-Marie , Maximov Ivan I. , Richard Geneviève , Andreassen Ole A. , Nordvik Jan E. , Westlye Lars T.
Published: April 2020

The macro- and microstructural architecture of human brain white matter undergoes substantial alterations throughout development and ageing. Most of our understanding of the spatial and temporal characteristics of these lifespan adaptations come from magnetic resonance imaging (MRI), including diffusion MRI (dMRI), which enables visualisation and quantification of brain white matter with unprecedented sensitivity and detail. However, with some notable exceptions, previous studies have relied on cross-sectional designs, limited age ranges, and diffusion tensor imaging (DTI) based on conventional single-shell dMRI. In this mixed cross-sectional and longitudinal study (mean interval: 15.2 months) including 702 multi-shell dMRI datasets, we combined complementary dMRI models to investigate age trajectories in healthy individuals aged 18 to 94 years (57.12% women). Using linear mixed effect models and machine learning based brain age prediction, we assessed the age-dependence of diffusion metrics, and compared the age prediction accuracy of six different diffusion models, including diffusion tensor (DTI) and kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), restriction spectrum imaging (RSI), spherical mean technique multi-compartment (SMT-mc), and white matter tract integrity (WMTI). The results showed that the age slopes for conventional DTI metrics (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [AD], radial diffusivity [RD]) were largely consistent with previous research, and that the highest performing advanced dMRI models showed comparable age prediction accuracy to conventional DTI. Linear mixed effects models and Wilk’s theorem analysis showed that the ‘FA fine’ metric of the RSI model and ‘orientation dispersion’ (OD) metric of the NODDI model showed the highest sensitivity to age. The results indicate that advanced diffusion models (DKI, NODDI, RSI, SMT mc, WMTI) provide sensitive measures of age-related microstructural changes of white matter in the brain that complement and extend the contribution of conventional DTI.
An alternative interpretation of the slow KaiB-KaiC binding of the cyanobacterial clock proteins
Authors: Koda Shin-ichi , Saito Shinji
Published: April 2020

The biological clock of cyanobacteria is composed of three proteins, KaiA, KaiB, and KaiC. The KaiB-KaiC binding brings the slowness into the system, which is essential for the long period of the circadian rhythm. However, there is no consensus as to the origin of the slowness due to the pre-binding conformational transition of either KaiB or KaiC. In this study, we propose a simple KaiB-KaiC binding scheme in a hexameric form with an attractive interaction between adjacent bound KaiB monomers, which is independent of KaiB’s conformational change. We then show that the present scheme can explain several important experimental results on the binding, including that used as evidence for the slow conformational transition of KaiB. The present result thus indicates that the slowness arises from KaiC rather than KaiB.
Endoplasmic Reticulum Associated Degradation (ERAD) Deficiency Promotes Mitochondrial Dysfunction and Transcriptional Rewiring in Human Hepatic Cells
Authors: Yang Xiaoqing , Liu Qingqing , Long Guangyu , Hu Yabin , Gu Zhenglong , Boisclair Yves R. , Long Qiaoming
Published: April 2020

Mitochondrial dysfunction has been associated with a variety of human diseases including neurodegeneration, diabetes, non-alcohol fatty liver disease (NAFLD) and cancer, but its underlying causes are incompletely understood. Endoplasmic reticular associated degradation (ERAD) is a protein quality control process essential for maintaining ER homeostasis. Using the human hepatic cell line HepG2 as a model, we show here that ERAD is critically required for mitochondrial function in mammalian cells. Pharmacological inhibition or genetic ablation of ERAD increases cell death under both basal conditions and in response to proinflammatory cytokines. Decreased viability of ERAD-deficient HepG2 cells was traced to impaired mitochondrial functions including reduced ATP production, enhanced reactive oxygen species (ROS) accumulation and increased mitochondrial outer membrane permeability (MOMP). Transcriptome profiling reveals widespread down-regulation in the expression of genes underpinning mitochondrial functions, and up-regulation in the genes with association to tumor growth and aggression. These results highlight a critical role for ERAD in maintaining mitochondrial functional and structural integrity and raise the possibility to improve cellular and organismal mitochondrial function via enhancing cellular ERAD capacity.
Contribution Evenness: A functional redundancy metric sensitive to trait stability in microbial communities
Authors: Royalty Taylor M. , Steen Andrew D.
Published: April 2020

The concept of functional redundancy has received considerable attention in both the macroecology and microbial ecology literature. As a result, multiple metrics of functional redundancy have been proposed. These vary in how they weight trait levels, species abundance, functional richness, and species richness. Here we present a new functional redundancy metric tailored for community-aggregated traits, which are traits that are quantified at the community level and can be quantitatively partitioned among species. We call this metric Contribution Evenness (CE) because it measures how evenly species contribute to a community-aggregated trait. As CE is an evenness measurement, it ranges from 0 and 1, where 0 corresponds to a single species contributing to a community-aggregated trait and 1 corresponds to all species contributing equally. Usingin silicosimulations of species extinctions, we demonstrate that CE reflects the stability of an ecosystem function to species extinction, a hypothesized ecological consequence of functional redundancy. As a positive control and to illustrate how CE can be used with sequence data, we analyzed the functional redundancy of eight nitrogen-transforming pathways using 2,631 metagenome-assembled genomes from 47 marine sites. CE for marine nitrogen cycle marker genes was consistent with our qualitative understanding of which nitrogen pathways are most functionally redundant in the ocean. We found that, on average, the NH4+assimilation pathway was the most functionally redundant (0.44 ± 0.08) while dissimilatory nitrate reduction was the least redundant (0.005 ± 0.005). As demonstrated here, CE provides a promising framework for measuring trait stability in microbiomes.
Chronic consumption of alcohol increase alveolar bone loss
Authors: de Almeida Juliano Milanezi , Pazmino Victor Fabrizio Cabrera , Novaes Vivian Cristina Noronha , Bomfim Suely Regina Mogami , Nagata Maria José Hitomi , Oliveira Fred Lucas Pinto , Ervolino Edilson
Published: April 2020

Background

This study evaluated the effects of the chronic consumption of different concentrations of alcohol on the experimental periodontitis (EP).

Methods

160 rats were divided into 4 groups: (EP-NT) rats with EP and no alcohol exposure; (EP-A14) rats with EP exposed to 14% alcohol; (EP-A25) rats with EP exposed to 25% alcohol; (EP-A36) rats with EP exposed to 36% alcohol. The animals from the EP-A14, EP-A25 and EP-A36 groups were subjected to different concentrations of alcohol 30 days before EP induction. The histological characteristics, percentage of bone in the furcation (PBF) and bone metabolism in the furcation region were evaluated. The PBF and tartrate-resistant acid phosphatase (TRAP) data were subjected to statistical analysis.

Results

The EP-A14, EP-A25 and EP-A36 groups had lower PBFs compared with the EP-NT group. A more severe inflammatory process and a greater number of TRAP+ cells were also observed. In the EP-A14, EP-A25 and EP-A36 groups, the inflammatory process became more severe as the ingested alcoholic concentration increased. An increase in RANKL immunostaining and a significantly higher number of TRAP+ cells were also observed.

Conclusion

We conclude that chronic alcohol consumption increases the severity of experimental periodontitis in a dose-dependent manner by increasing the magnitude of local inflammatory responses and stimulating alveolar bone resorption.
Molecular basis for the distinct cellular functions of the Lsm1-7 and Lsm2-8 complexes
Authors: Montemayor Eric J. , Virta Johanna M. , Hayes Samuel M. , Nomura Yuichiro , Brow David A. , Butcher Samuel E.
Published: April 2020

Eukaryotes possess eight highly conserved Lsm (like Sm) proteins that assemble into circular, heteroheptameric complexes, bind RNA, and direct a diverse range of biological processes. Among the many essential functions of Lsm proteins, the cytoplasmic Lsm1-7 complex initiates mRNA decay, while the nuclear Lsm2-8 complex acts as a chaperone for U6 spliceosomal RNA. It has been unclear how these complexes perform their distinct functions while differing by only one out of seven subunits. Here, we elucidate the molecular basis for Lsm-RNA recognition and present four high-resolution structures of Lsm complexes bound to RNAs. The structures of Lsm2-8 bound to RNA identify the unique 2′,3′ cyclic phosphate end of U6 as a prime determinant of specificity. In contrast, the Lsm1-7 complex strongly discriminates against cyclic phosphates and tightly binds to oligouridylate tracts with terminal purines. Lsm5 uniquely recognizes purine bases, explaining its divergent sequence relative to other Lsm subunits. Lsm1-7 loads onto RNA from the 3′ end and removal of the Lsm1 C-terminal region allows Lsm1-7 to scan along RNA, suggesting a gated mechanism for accessing internal binding sites. These data reveal the molecular basis for RNA binding by Lsm proteins, a fundamental step in the formation of molecular assemblies that are central to eukaryotic mRNA metabolism.
Dyrk1b is a key Regulatory Kinase Integrating Fgf, Shh and mTORC1 signaling in Skeletal Muscle Development and Homeostasis
Authors: Bhat Neha , Narayanan Anand , Fathzadeh Mohsen , Srivastava Anup , Mani Arya
Published: April 2020

The advent of human genetics has provided unprecedented opportunities for discovery of novel disease pathways. Mutations inDYRK1Bhave been associated with metabolic syndrome and sarcopenic obesity in humans, underscoring the critical role of the encoded protein in skeletal muscle development and homeostasis. By the novel creation of Dyrk1b knockout zebrafish models we demonstrate that Dyrk1b kinase activity is critical for specification of the paraxialmyoD. Mechanistically, Dyrk1b mediates and amplifies Fgf signaling in the paraxial domain by the transcriptional suppression of its negative feedback inhibitorsprouty1. In the adaxialmyoDdomain, Dyrk1b amplifies Shh signaling and partially rescues defects caused by its disruption. The investigations of C2C12 terminal differentiation revealed that Dyrk1b also plays a critical role in myofiber fusion. Combined biochemical and proteomic analysis of C2C12 myoblasts undergoing differentiation showed that Dyrk1b kinase activation is induced by shh inhibition, and triggers differentiation by inhibiting mTOR, subsequent upregulation of 4e-bp1 and induction of autophagy. In conclusion, we demonstrate that Dyrk1b plays a critical role in sustaining myocyte specification and differentiation by integrating Fgf, Shh and mTORC1 signaling pathways.
Modulation of cell adhesion and migration by poly-dispersed-acid-functionalized-single-walled carbon nanotubes in lung epithelial cells
Authors: Behera Sushreesangita P. , Saxena Rajiv K.
Published: April 2020

Epithelial cell lining of the lung alveoli is under constant onslaught of airborne pathogens and pollutants that may cause injury and disruption of the epithelial lining. Repair mechanisms involve proliferation and migration of nearby healthy epithelial cells to the site of injury. Using murine LA4 and human A549 lung epithelial cell lines, andin vitromodels of cell migration we have examined the modulation of cellular adhesion and migration by poly-dispersed acid-functionalized single-walled carbon nanotubes (AF-SWCNTs). Flow cytometric and confocal microscopy studies indicated that AF-SWCNTs were efficiently internalized by both cell lines and were localized essentially in the cytoplasmic area. In the scratch wound repair model, exposure to AF-SWCNTs blocked the filling of the scratched area of the cellular monolayers in both cells. Behaviour of the cells around the scratch area was examined in by live-cell imaging time-lapse micrography. The results indicated active cell proliferation around the scratch area that was totally blocked by AF-SWCNTs in LA4 cells and significantly inhibited in A549 cells. Cell migration across a porous membrane in transwell assay system also indicated a marked inhibition of migration of both cells across the membrane. Effect of AF-SWCNTs on the expression levels of important cell proteins involved in cell migration and adhesion were examined by western blotting and immunofluorescence staining. Expressions of proteins like β-Catenin, NM-Myosin and Vimentin that play crucial role in cell migration were suppressed in AF-SWCNTs-exposed cells whereas the expression levels of E-cadherin and Claudin-1, involved in cell-cell adhesion remained unaltered. Our results provide an insight into the mechanism of repair of lung epithelial cell layers.