bluuebunny/crossref_metadata_2025_split huggingface dataset:
Respiration aligns perception with neural excitability
Authors: Kluger Daniel S. , Balestrieri Elio , Busch Niko A. , Gross Joachim 
Published: March 2021

AbstractRecent studies from the field of interoception have highlighted the link between bodily and neural rhythms during action, perception, and cognition. The mechanisms underlying functional body-brain coupling, however, are poorly understood, as are the ways in which they modulate behaviour. We acquired respiration and human magnetoencephalography (MEG) data from a near-threshold spatial detection task to investigate the trivariate relationship between respiration, neural excitability, and performance. Respiration was found to significantly modulate perceptual sensitivity as well as posterior alpha power (8 – 13 Hz), a well-established proxy of cortical excitability. In turn, alpha suppression prior to detected vs undetected targets underscored the behavioural benefits of heightened excitability. Notably, respiration-locked excitability changes were maximised at a respiration phase lag of around - 30° and thus temporally preceded performance changes. In line with interoceptive inference accounts, these results suggest that respiration actively aligns sampling of sensory information with transient cycles of heightened excitability to facilitate performance.
A tau class Glutathione-S-Transferase (OsGSTU5) acts as a negative regulator of VirE2 interaction with T-DNA duringAgrobacteriuminfection in rice
Authors: Tiwari Madhu , Gautam Neelam , Indoliya Yuvraj , Kidwai Maria , Mishra Arun Kumar , Chakrabarty Debasis 
Published: March 2021

AbstractDuringAgrobacterium-mediated transformation (AMT), T-DNA along with several virulence proteins like VirD2, VirE2, VirE3, VirD5, and VirF enter into the plant cytoplasm. VirE2 is supposed to serve as single-stranded DNA binding (SSB) protein and assist the cytoplasmic trafficking of T-DNA inside the host cell. In the present study, a rice glutathione-S-transferase (OsGSTU5) that interacts with VirE2 protein in plant cytoplasm has been identified. OsGSTU5 is observed to be involved in post-translational glutathionylation of VirE2 protein (gVirE2).In silicoanalysis revealed that ‘gVirE2+ssDNA’ complex is structurally less stable than ‘VirE2+ ssDNA’ complex. The gel shift activity confirms the attenuated SSB property of gVirE2 over VirE2 protein underin vitrocondition. Moreover, knock-down and overexpressionOsGSTU5phenotypes of rice showed increased and decreased T-DNA expression, respectively afterAgrobacteriuminfection. The present finding convincingly establishes the role of OsGSTU5 as defense protein in rice that can further serve as an important target for modulation of AMT efficiency in rice.
Patterns and mechanisms underlying ecoregion delineation in North American freshwater plants
Authors: Alahuhta Janne , García–Girón Jorge 
Published: March 2021

AbstractAimBiogeographical regionalisations are actively studied in different ecosystems, because they increase our understanding on fundamental broad□scale patterns and can help us in the establishment of conservation areas. Thus, we studied how well existing freshwater ecoregions describe geographical delineation for inland water plants and which ecogeographical gradients explain them.LocationNorth America, excluding Mexico and remote islands.TaxonFreshwater vascular plants of all taxa and different functional groups.MethodsUsing newly available fine–grained data on freshwater plant distributions, we calculated internal homogeneity and cross–boundary heterogeneity among neighbouring ecoregions. We further integrated measures of community dissimilarity to assess whether the degree of within–ecoregion homogeneity and distinctness are driven by their relationships to species replacements and richness differences, and explored how a complex suite of ecogeographical mechanisms and plant life forms affect ecoregion delineation using spatially explicit regression routines.ResultsWe found a clear geographical patterning of ecoregion robustness for North American freshwater plants, with their communities being more internally homogeneous and more similar to one another in polar and subtropical inland waters. Surprisingly, the degree of internal homogeneity and ecoregion distinctness were almost equally driven by species replacements and richness differences. Considering different life forms, ecoregion delineation performed best for emergent and floating–leaved plants. Finally, within–ecoregion homogeneity and distinctness were best explained by annual mean temperature and terrain ruggedness, respectively, with mean water alkalinity, ecoregion area and Late Quaternary Ice Age legacies having supplementary effects.Main conclusionsOur findings emphasise that geographical regionalisations founded on a particular organismal group are not applicable for all taxa. Our study is a promising starting point for further investigations of geographical delineations for different freshwater taxa. These updated regionalisations can then be used for conserving different biotas in freshwaters, which are currently among the most threatened ecosystems in the world.Statement of significanceIn biogeographical regionalisation biota is categorized to meaningful geographical units, such as ecoregions. However, ecoregions delineated for a particular group of organisms may not be applicable to another assemblages. We studied how ecoregions founded on fish are suitable for freshwater plants across North America. Our findings suggest that these ecoregions did not show consistent robustness for freshwater plants in North America. This study is a promising starting point for further investigations of geographical delineations for different freshwater taxa, having also value in conservation planning and management.
Adjustment of spurious correlations in co-expression measurements from RNA-Sequencing data
Authors: Hsieh Ping-Han , Lopes-Ramos Camila Miranda , Zucknick Manuela , Sandve Geir Kjetil , Glass Kimberly , Kuijjer Marieke Lydia 
Published: March 2021

1AbstractGene co-expression measurements are widely used in computational biology to identify coordinated expression patterns across a group of samples, which may indicate that these genes are controlled by the same transcriptional regulatory program, or involved in common biological processes. Gene co-expression is generally estimated from RNA-Sequencing data, which are commonly normalized to remove technical variability. Here, we demonstrate that certain normalization methods, in particular quantile-based methods, can introduce false-positive associations between genes, and that this can consequently hamper downstream co-expression network analysis. Quantile-based normalization can, however, be extremely powerful. In particular when preprocessing large-scale heterogeneous data, quantile-based normalization methods such as smooth quantile normalization can be applied to remove technical variability while maintaining global differences in expression for samples with different biological attributes. We therefore developed SNAIL, a normalization method based on smooth quantile normalization specifically designed for modeling of co-expression measurements. We show that SNAIL avoids formation of false-positive associations in co-expression as well as in downstream network analyses. Using SNAIL, one can avoid arbitrary gene filtering and retain associations to genes that only express in small subgroups of samples. This highlights the method’s potential future impact on network modeling and other association-based approaches in large-scale heterogeneous data.
Genome-wide identification of Arabidopsis non-AUG-initiated upstream ORFs with evolutionarily conserved regulatory sequences that control protein expression levels
Authors: Hiragori Yuta , Takahashi Hiro , Hayashi Noriya , Sasaki Shun , Nakao Kodai , Motomura Taichiro , Yamashita Yui , Naito Satoshi , Onouchi Hitoshi 
Published: March 2021

ABSTRACTUpstream open reading frames (uORFs) are short ORFs found in the 5′-UTRs of many eukaryotic transcripts and can influence the translation of protein-coding main ORFs (mORFs). Recent genome-wide ribosome profiling studies have revealed that thousands of uORFs initiate translation at non-AUG start codons. However, the physiological significance of these non-AUG uORFs has so far been demonstrated for only a few of them. It is conceivable that physiologically important non-AUG uORFs are evolutionarily conserved across species. In this study, using a combination of bioinformatics and experimental approaches, we searched the Arabidopsis genome for non-AUG-initiated uORFs with conserved sequences that control the expression of the mORF-encoded proteins. As a result, we identified four novel regulatory non-AUG uORFs. Among these, two exerted repressive effects on mORF expression in an amino acid sequence-dependent manner. These two non-AUG uORFs are likely to encode regulatory peptides that cause ribosome stalling, thereby enhancing their repressive effects. In contrast, one of the identified regulatory non-AUG uORFs promoted mORF expression by alleviating the inhibitory effect of a downstream AUG-initiated uORF. These findings provide insights into the mechanisms that enable non-AUG uORFs to play regulatory roles despite their low translation initiation efficiencies.
Neural activity during story listening is synchronized across individuals despite acoustic masking
Authors: Irsik Vanessa C. , Johnsrude Ingrid S. , Herrmann Björn 
Published: March 2021

AbstractOlder people with hearing problems often experience difficulties understanding speech in the presence of background sound. As a result, they may disengage in social situations, which has been associated with negative psychosocial health outcomes. Measuring listening (dis-)engagement during challenging listening situations has received little attention thus far. We recruit young, normal-hearing human adults (both sexes) and investigate how speech intelligibility and engagement during naturalistic story listening is affected by the level of acoustic masking (12-talker babble) at different signal-to-noise ratios (SNRs). In Experiment 1, we observed that word-report scores were above 80% for all but the lowest SNR (-3 dB SNR) we tested, at which performance dropped to 54%. In Experiment 2, we calculated inter-subject correlation (ISC) using electroencephalography (EEG) data to identify dynamic spatial patterns of shared neural activity evoked by the stories. ISC has previously been used as a neural measure of participants’ engagement with naturalistic materials. Our results show that ISC was stable across all but the lowest SNRs, despite reduced speech intelligibility. Comparing ISC and intelligibility demonstrated that word-report performance declined more strongly with decreasing SNR compared to ISC. Our measure of neural engagement suggests that individuals remain engaged in story listening despite missing words due to background noise. Our work provides a potentially fruitful approach to investigate listener engagement with naturalistic, spoken stories that may be used to investigate (dis)engagement in older adults with hearing impairment.
INPP4B drives lysosome biogenesis to restrict leukemic stem cell differentiation and promote leukemogenesis
Authors: Woolley John F. , Chen Keyue , Saffi Golam T. , Genc Gizem E. , Lee Daniel K.C. , Dzneladze Irakli , He Ruijuan , Chow Jonathan T.S. , Gabra Martino M. , Hi Son Meong , Melo Ché M.P. , Newell Candaice A. , He Aobo , Schoof Erwin M. , Xie Stephanie Z. , Mangialardi Emily M. , Kotlyar Max , Rashid Ayesha , Gams Miki. S. , Vacher Jean , Guidos Cynthia J. , Jurisica Igor , Dick John E. , Botelho Roberto J. , Minden Mark D. , Salmena Leonardo 
Published: March 2021

AbstractSignaling pathways that control vital features of leukemic stem cells including multipotency, self-renewal, clonal expansion and quiescence remain unclear. Emerging studies illustrate critical roles for lysosomes in hematopoietic and leukemic stem cell fate. By investigating consequences ofINPP4Balterations in AML, we have discovered its role in driving leukemic ‘stemness’. We observed thatINPP4Bis highly expressed leukemic stem cell populations andInpp4b-deficeint leukemias demonstrate increased disease latency, reduced leukemia initiating potential which is associated with a differentiated leukemic phenotype. Molecular analyses show thatInpp4b-deficient leukemias have compromised lysosomal gene expression, lysosomal content, and lysosomal activity. Our discovery of a novel pathway linking INPP4B, lysosomal biogenesis and leukemic stemness, provides a mechanism to explain the association of highINPP4Bexpression with poor AML prognosis, and highlights novel patient stratification strategies and LSC-specific leukemic therapies.Key PointsOur findings highlight a novel pathway linking INPP4B, lysosomal function and leukemic stemness that explains the prognostic role of INPP4B in AML.Our data reveal the utility of INPP4B as a biomarker of aggressive AML and provide a rationale to explore INPP4B and its associated function in lysosome biology as novel strategies to target LSC and AML
DNA methylation and demethylation underlie the sex difference in estrogen receptor alpha in the arcuate nucleus
Authors: Cortes Laura R. , Cisternas Carla D. , Cabahug Iagn N.K.V. , Mason Damian , Ramlall Emma K. , Castillo-Ruiz Alexandra , Forger Nancy G. 
Published: March 2021

AbstractIntroductionNeurons expressing estrogen receptor (ER) α in the arcuate nucleus (ARC) of the hypothalamus sex-specifically control energy homeostasis and bone density. Females have more of these neurons than do males, but how this sex difference develops is unknown.ObjectiveWe tested the hypothesis that DNA methylation and/or demethylation control the development of a sex difference in ERα in the ARC.MethodsERα immunoreactive neurons were quantified at birth and at weaning in male, female and testosterone-treated female mice that received neonatal, intracerebroventricular injections of vehicle or zebularine, a DNA methyltransferase inhibitor. Methylation status ofEsr1was determined in the ARC and ventromedial hypothalamus (VMH) using bisulfite conversion of DNA followed by pyrosequencing. Small interfering RNAs against ten-eleven translocases were used to examine effects of demethylation on ERα cell number.ResultsA sex difference in ERα cell number in the ARC, favoring females, developed between birth and weaning and was due to programming effects of testosterone. Zebularine treatment eliminated the sex difference in ERα in the ARC at weaning bydecreasingERαin femalesto male-like levels. Previously, the same treatmentincreasedERαin malesin the VMH. A promoter region ofEsr1exhibited sex differences in opposite directions in percent of total methylation in the ARC (females > males) and VMH (males > females). Moreover, neonatal inhibition of demethylation increased ERα in the ARC of males.ConclusionDNA methylation and demethylation regulate ERα cell number in the ARC, and methyl marks may paradoxically activateEsr1in this region.
Neural speech tracking shifts from the syllabic to the modulation rate of speech as intelligibility decreases
Authors: Schmidt Fabian , Chen Ya-Ping , Keitel Anne , Rösch Sebastian , Hannemann Ronny , Serman Maja , Hauswald Anne , Weisz Nathan 
Published: March 2021

ABSTRACTThe most prominent acoustic features in speech are intensity modulations, represented by the amplitude envelope of speech. Synchronization of neural activity with these modulations is vital for speech comprehension. As the acoustic modulation of speech is related to the production of syllables, investigations of neural speech tracking rarely distinguish between lower-level acoustic (envelope modulation) and higher-level linguistic (syllable rate) information. Here we manipulated speech intelligibility using noise-vocoded speech and investigated the spectral dynamics of neural speech processing, across two studies at cortical and subcortical levels of the auditory hierarchy, using magnetoencephalography. Overall, cortical regions mostly track the syllable rate, whereas subcortical regions track the acoustic envelope. Furthermore, with less intelligible speech, tracking of the modulation rate becomes more dominant. Our study highlights the importance of distinguishing between envelope modulation and syllable rate and provides novel possibilities to better understand differences between auditory processing and speech/language processing disorders.Abstract Figure
A multitask transfer learning framework for novel virus-human protein interactions
Authors: Dong Ngan Thi , Khosla Megha 
Published: March 2021

AbstractUnderstanding the interaction patterns between a particular virus and human proteins plays a crucial role in unveiling the underlying mechanism of viral infection. This could further help in developing treatments of viral diseases. The main issues in tackling it as a machine learning problem is the scarcity of training data as well input information of the viral proteins. We overcome these limitations by exploiting powerful statistical protein representations derived from a corpus of around 24 Million protein sequences in a multi task framework. Our experiments on 7 varied benchmark datasets support the superiority of our approach.
A covariation analysis reveals elements of selectivity in quorum sensing systems
Authors: Wellington Miranda S , Cong Q , Schaefer AL , MacLeod EK , Zimenko A , Baker D , Greenberg EP 
Published: March 2021

AbstractMany bacteria communicate with kin and coordinate group behaviors through a form of cell-cell signaling called acyl-homoserine lactone (AHL) quorum sensing (QS). In these systems, a signal synthase produces an AHL to which its paired receptor selectively responds. Selectivity is fundamental to cell signaling. Despite its importance, it has been challenging to determine how this selectivity is achieved and how AHL QS systems evolve and diversify. We hypothesized that we could use covariation within the protein sequences of AHL synthases and receptors to identify selectivity residues. We began by identifying about 6,000 unique synthase-receptor pairs. We then used the protein sequences of these pairs to identify covariation patterns and mapped the patterns onto the LasI/R system fromPseudomonas aeruginosaPAO1. The covarying residues in both proteins cluster around the ligand binding sites. We demonstrate that these residues are involved in system selectivity toward the cognate signal and go on to engineer the Las system to both produce and respond to an alternate AHL signal. We have thus demonstrated a new application for covariation methods and have deepened our understanding of how communication systems evolve and diversify.
Characterization of a glycolipid glycosyltransferase with broad substrate specificity from the marine bacteriumCandidatusPelagibacter sp. HTCC7211
Authors: Wei Tao , Zhao Caimeng , Quareshy Mussa , Wu Nan , Huang Shen , Zhao Yuezhe , Yang Pengfei , Mao Duobin , Chen Yin 
Published: March 2021

AbstractIn the marine environment, phosphorus availability significantly affects the lipid composition in many cosmopolitan marine heterotrophic bacteria, including members of the SAR11 clade and the Roseobacter clade. Under phosphorus stress conditions, non-phosphorus sugar-containing glycoglycerolipids are substitutes for phospholipids in these bacteria. Although these glycoglycerolipids play an important role as surrogates for phospholipids under phosphate deprivation, glycoglycerolipid synthases in marine microbes are poorly studied. In the present study, we biochemically characterized a glycolipid glycosyltransferase (GTcp) from the marine bacteriumCandidatusPelagibacter sp. HTCC7211, a member of the SAR11 clade. Our results showed that GTcpis able to act as a multifunctional enzyme by synthesizing different glycoglycerolipids with UDP-glucose, UDP-galactose, or UDP-glucuronic acid as sugar donors and diacylglycerol as the acceptor. Analyses of enzyme kinetic parameters demonstrated that Mg2+notably changes the enzyme’s affinity for UDP-glucose, which improves its catalytic efficiency. Homology modelling and mutational analyses revealed binding sites for the sugar donor and the diacylglycerol lipid acceptor, which provided insights into the retaining mechanism of GTcpwith its GT-B fold. A phylogenetic analysis showed that GTcpand its homologs form a group in the GT4 glycosyltransferase family. These results not only provide new insights into the glycoglycerolipid synthesis mechanism in lipid remodelling, but also describe an efficient enzymatic tool for future synthesis of bioactive molecules.ImportanceThe bilayer formed by membrane lipids serves as the containment unit for living microbial cells. In the marine environment, it has been firmly established that phytoplankton and heterotrophic bacteria can substitute phospholipids with non-phosphorus sugar-containing glycoglycerolipids in response to phosphorus limitation. However, little is known about how these glycoglycerolipids are synthesized. Here, we determined the biochemical characteristics of a glycolipid glycosyltransferase (GTcp) from the marine bacteriumCandidatusPelagibacter sp. HTCC7211. GTcpand its homologs form a group in the GT4 glycosyltransferase family, and can synthesize neutral glycolipids (MGlc-DAG and MGal-DAG) and an acidic glycolipid (MGlcA-DAG). We also uncover the key residues for DAG-binding through molecular docking, site-direct mutagenesis and subsequent enzyme activity assays. Our data provide new insights into the glycoglycerolipid synthesis mechanism in lipid remodelling.
α2δ-2 is Required for Depolarization-induced Suppression of Excitation in Purkinje cells
Authors: Beeson Kathleen A. , Westbrook Gary L. , Schnell Eric 
Published: March 2021

Abstractα2δ proteins (CACNA2D1-4) are required for normal neurological function, although how they control neuronal output remains unclear. Using whole-cell recordings of mouse Purkinje cells, we show α2δ-2 is required for functional coupling of postsynaptic voltage-dependent calcium entry with effector mechanisms controlling two different outputs, depolarization-induced suppression of excitation mediated by endocannabinoid signaling, and spike afterhyperpolarization generated by calcium-dependent potassium channels. Our findings indicate an important role for α2δ-2 proteins in regulating functional postsynaptic calcium channel-coupling in neurons.Significance StatementCalcium influx via membrane voltage-dependent calcium channels drives numerous neuronal processes by signaling through calcium-dependent effector molecules. Signal precision is achieved in part by calcium channel-effector coupling. In mouse Purkinje cell neurons, we show that neuronal α2δ-2 protein functionally couples calcium entry to two different postsynaptic calcium-dependent signals, retrograde endocannabinoid signaling and the action potential afterhyperpolarization. Our findings provide new insights about the control of calcium channel-effector coupling as well as new roles for α2δ-2 proteins in neurons.