bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multisensory processes can compensate for attention deficits in schizophrenia
Authors: Moran James K. , Keil Julian , Masurovsky Alexander , Gutwinski Stefan , Montag Christiane , Senkowski Daniel 
Published: August 2020

AbstractStudies on schizophrenia (SCZ) and aberrant multisensory integration (MSI) show conflicting results. These divergent results are potentially confounded by attention deficits in SCZ. To test this, we examined the interplay between MSI and intersensory attention (IA) in healthy controls (N=27) and in SCZ (N=27). Evoked brain potentials to unisensory-visual (V), unisensory-tactile (T) or bisensory VT stimuli were measured with high density electroencephalography, whilst participants attended block-wise to either visual or tactile inputs. Behaviourally, IA effects in SCZ are uncompromised for bisensory stimuli, but diminished for unisensory stimuli. At the neural level, we observed reduced IA effects for bisensory stimuli over mediofrontal scalp regions (230-320ms) in SCZ. The analysis of MSI revealed multiple phases of integration over occipital and frontal scalp regions (240-364ms), with comparable performance between HC and SCZ. The magnitudes of IA and MSI effects were both positively related to the behavioural performance in SCZ, indicating that IA and MSI mutually facilitate bisensory stimulus processing. Our study suggests that widely intact MSI, which facilitates stimulus processing, can compensate for top-down attention deficits in SCZ. Further, the interplay of IA and MSI implies that differences in attentional demands may account for previous conflicting findings on MSI in schizophrenia.
The risks of using the chi-square periodogram to estimate the period of biological rhythms
Authors: Tackenberg Michael C. , Hughey Jacob J. 
Published: August 2020

AbstractThe chi-square periodogram (CSP), developed over 40 years ago, continues to be one of the most popular methods to estimate the period of circadian (circa 24-h) rhythms. Previous work has indicated the CSP is sometimes less accurate than other methods, but understanding of why and under what conditions remains incomplete. Using simulated rhythmic time-courses, we found that the CSP is prone to underestimating the period in a manner that depends on the true period and the length of the time-course. This underestimation bias is most severe in short time-courses (e.g., 3 days), but is also visible in longer simulated time-courses (e.g., 12 days) and in experimental time-courses of mouse wheel-running and ex vivo bioluminescence. We traced the source of the bias to discontinuities in the periodogram that are related to the number of time-points the CSP uses to calculate the observed variance for a given test period. By revising the calculation to avoid discontinuities, we developed a new version, the greedy CSP, that shows reduced bias and improved accuracy. Nonetheless, even the greedy CSP tended to be less accurate on our simulated time-courses than an alternative method, namely the Lomb-Scargle periodogram. Thus, although our study describes a major improvement to a classic method, it also suggests that users should generally avoid the CSP when estimating the period of biological rhythms.
The yeast ISW1b ATP-dependent chromatin remodeler is critical for nucleosome spacing and dinucleosome resolution
Authors: Eriksson Peter R. , Clark David J. 
Published: August 2020

AbstractIsw1 and Chd1 are ATP-dependent nucleosome-spacing enzymes required to establish regular arrays of phased nucleosomes near transcription start sites of yeast genes. Cells lacking both Isw1 and Chd1 have extremely disrupted chromatin, with weak phasing, irregular spacing and a propensity to form closed-packed dinucleosomes. The Isw1 ATPase subunit occurs in two different remodeling complexes: ISW1a (composed of Isw1 and Ioc3) and ISW1b (composed of Isw1, Ioc2 and Ioc4). The Ioc4 subunit of ISW1b binds preferentially to the H3-K36me3 mark. Here we show that ISW1b is primarily responsible for setting nucleosome spacing and resolving close-packed dinucleosomes, whereas ISW1a plays only a minor role. ISW1b and Chd1 make additive contributions to dinucleosome resolution, such that neither enzyme is capable of resolving all dinucleosomes on its own. Loss of the Set2 H3-K36 methyltransferase partly phenocopies loss of Ioc4, resulting in increased dinucleosome levels with only a weak effect on nucleosome spacing, suggesting that Set2-mediated H3-K36 trimethylation contributes to ISW1b-mediated dinucleosome separation. The H4 tail domain is required for normal nucleosome spacing but not for dinucleosome resolution. We conclude that the nucleosome spacing and dinucleosome resolving activities of ISW1b and Chd1 are critical for normal global chromatin organisation.
WgLink: reconstructing whole-genome viral haplotypes usingL0+L1-regularization
Authors: Cao Chen , Greenberg Matthew , Long Quan 
Published: August 2020

AbstractMany tools can reconstruct viral sequences based on next generation sequencing reads. Although existing tools effectively recover local regions, their accuracy suffers when reconstructing the whole viral genomes (strains). Moreover, they consume significant memory when the sequencing coverage is high or when the genome size is large. We present WgLink to meet this challenge. WgLink takes local reconstructions produced by other tools as input and patches the resulting segments together into coherent whole-genome strains. We accomplish this using anL0+L1-regularized regression synthesizing variant allele frequency data with physical linkage between multiple variants spanning multiple regions simultaneously. WgLink achieves higher accuracy than existing tools both on simulated and real data sets while using significantly less memory (RAM) and fewer CPU hours. Source code and binaries are freely available athttps://github.com/theLongLab/wglink.
Parallel processing of quickly and slowly mobilized reserve vesicles in hippocampal synapses
Authors: Rodríguez Gotor Juan José , Mahfooz Kashif , Pérez-Otaño Isabel , Wesseling John F. 
Published: August 2020

AbstractVesicles within presynaptic terminals are thought to be segregated into a variety of readily releasable and reserve pools. The nature of the pools and trafficking between them is not well understood, but pools that are slow to mobilize when synapses are active are often assumed to feed pools that are mobilized more quickly, in a series. However, electrophysiological studies of synaptic transmission have suggested instead a parallel organization where vesicles within slowly and quickly mobilized reserve pools would separately feed independent reluctant- and fast-releasing subdivisions of the readily releasable pool. Here we use FM-dyes to confirm the existence of multiple reserve pools at hippocampal synapses and a parallel organization that prevents intermixing between the pools, even when stimulation is intense enough to drive exocytosis at the maximum rate. The experiments additionally demonstrate extensive heterogeneity among synapses in the relative sizes of the slowly and quickly mobilized reserve pools, which suggests equivalent heterogeneity in the numbers of reluctant and fast-releasing readily releasable vesicles that may be relevant for understanding information processing and storage.
BamA and BamD are essential for the secretion of trimeric autotransporter adhesins
Authors: Rooke Jessica L. , Icke Chris , Wells Timothy J. , Rossiter Amanda E. , Browning Douglas F. , Morris Faye C. , Leo Jack C. , Schütz Monika S. , Autenrieth Ingo B , Cunningham Adam F. , Linke Dirke , Henderson Ian R. 
Published: August 2020

AbstractThe BAM complex inEscherichia coliis composed of five proteins, BamA-E. BamA and BamD are essential for cell viability and are required for the assembly of β-barrel outer membrane proteins. Consequently, BamA and BamD are indispensable for secretion via the classical autotransporter pathway (Type 5a secretion). In contrast, BamB, BamC and BamE are not required for the biogenesis of classical autotransporters. Recently, we demonstrated that TamA, a homologue of BamA, and its partner protein TamB, were required for efficient secretion of proteins via the classical autotransporter pathway. The trimeric autotransporters are a subset of the Type 5-secreted proteins. Unlike the classical autotransporters, they are composed of three identical polypeptide chains which must be assembled together to allow secretion of their cognate passenger domains. In contrast to the classical autotransporters, the role of the Bam and Tam complex components in the biogenesis of the trimeric autotransporters has not been investigated fully. Here, using theSalmonella entericatrimeric autotransporter SadA and the structurally similar YadA protein ofYersiniaspp., we identify the importance of BamA and BamD in the biogenesis of the trimeric autotransporters and reveal that BamB, BamC, BamE, TamA and TamB are not required for secretion of functional passenger domain on the cell surface.ImportanceThe secretion of trimeric autotransporters (TAA’s) has yet to be fully understood. Here we show that efficient secretion of TAAs requires the BamA and D proteins, but does not require BamB, C or E. In contrast to classical autotransporter secretion, neither trimeric autotransporter tested required TamA or B proteins to be functionally secreted.
ConvertingEscherichia coliMG1655 into a chemical overproducer through inactivating defense system against exogenous DNA
Authors: Wang Jingge , Huang Chaoyong , Guo Kai , Ma Lianjie , Meng Xiangyu , Wang Ning , Huo Yi-Xin 
Published: August 2020

AbstractEscherichia colistrain K-12 MG1655 has been proposed as an appropriate host strain for industrial production. However, the direct application of this strain suffers from the transformation inefficiency and plasmid instability. Herein, we conducted genetic modifications at a serial of loci of MG1655 genome, generating a robust and universal host strain JW128 with higher transformation efficiency and plasmid stability that can be used to efficiently produce desired chemicals after introducing the corresponding synthetic pathways. Using JW128 as the host, the titer of isobutanol reached 5.76 g/L in shake-flask fermentation, and the titer of lycopene reached 1.91 g/L in test-tube fermentation, 40-fold and 5-fold higher than that of original MG1655, respectively. These results demonstrated JW128 is a promising chassis for high-level production of value-added chemicals.
Vortex chip incorporating an orthogonal turn for size-based isolation of circulating cells
Authors: Rastogi Navya , Seth Pranjal , Bhat Ramray , Sen Prosenjit 
Published: August 2020

AbstractLabel-free separation of rare cells (e.g. circulating tumor cells (CTCs)) based on their size is attractive due to its wider applicability, simpler sample preparation, faster turnaround, better efficiency and higher purity. Amongst cognate protocols for the same, vortex-trapping based techniques offer high throughput but operate at high flow velocities where the resulting hydrodynamic shear stress is likely to damage cells and compromise their viability for subsequent assays. We present here an orthogonal vortex chip which can carry out size-differentiated trapping at significantly lower (38% of previously reported) flow velocities. Fluid flowing through the chip is constrained to exit the trapping chamber at right angles to that of its entry. Such a flow configuration leads to the formation of vortex in the chamber. Above a critical flow velocity, larger particles are trapped in the vortex whereas smaller particles get ejected with the flow: we call this phenomenon the turn-effect. We have characterized the critical velocities for trapping of cells and particles of different sizes on chips with distinct entry-exit configurations. Optimal architectures for stable vortex trapping at low flow velocities are identified. We explain how shear-gradient lift, centrifugal and Dean flow drag forces contribute to the turn-effect by acting on cells which pushes them into specific vortices in a size- and velocity-dependent fashion. Finally, we demonstrate selective trapping of human breast cancer cells mixed with whole blood at low-concentration. Our findings suggest that the device shows promise for the gentle isolation of rare cells from blood.
Dendritic spikes in apical oblique dendrites of cortical layer 5 pyramidal neurons
Authors: Castañares Michael Lawrence G. , Stuart Greg J. , Daria Vincent R. 
Published: August 2020

AbstractDendritic spikes in layer 5 pyramidal neurons (L5PNs) play a major role in cortical computation. While dendritic spikes have been studied extensively in apical and basal dendrites of L5PNs, whether oblique dendrites, which ramify in the input layers of the cortex, also generate dendritic spikes is unknown. Here we report the existence of dendritic spikes in apical oblique dendrites of L5PNs.In silicoinvestigations indicate that oblique branch spikes are triggered by brief, low-frequency action potential (AP) trains (~40 Hz) and are characterized by a fast sodium spike followed by activation of voltage-gated calcium channels.In vitroexperiments confirmed the existence of oblique branch spikes in L5PNs during brief AP trains at frequencies of around 60 Hz. Oblique branch spikes offer new insights into branch-specific computation in L5PNs and may be critical for sensory processing in the input layers of the cortex.
Protocol for clustering of non-unified protein sequences through memory-map guided deep learning
Authors: Prakash Om 
Published: August 2020

ABSTRACTProtocol established and validated for clustering of non-unified protein sequences through memorymap guided deep learning. Data evaluated belongs to the disease causing proteins/genes from human hormonal system. Possibilities for future experiments validation was found for genes as: ACTHR, AGMX1, ATK, BPK, DPDE3, ERBA2, FSHB, GH1, GHSR, GNAS1, GSP, HANF, LCGR, LGR2, LGR3, LHRHR, NR1A2, PKR1, PRKAR1, RNF216, SBP2, SECISBP2, THR1, THRB, TPIT, TRIAD3, TSE1, UBCE7IP1, XAP2, and ZIN. Protocol is recommended for implementation with small to large dataset (protein/ DNA/ RNA sequences of unified or non-unified length) with unclassified data flags.
Nitric oxide prevents aortic valve calcification by S-nitrosylation of USP9X to activate NOTCH signaling
Authors: Majumdar Uddalak , Manivannan Sathiyanarayanan , Basu Madhumita , Ueyama Yukie , Blaser Mark C. , Cameron Emily , McDermott Michael R. , Lincoln Joy , Cole Susan E. , Wood Stephen , Aikawa Elena , Lilly Brenda , Garg Vidu 
Published: August 2020

AbstractCalcific aortic valve disease (CAVD) is an increasingly prevalent condition and endothelial dysfunction is implicated in its etiology. We previously identified nitric oxide (NO) as a calcification inhibitor by its activation ofNOTCH1, which is genetically linked to human CAVD. Here, we show that NO rescues calcification by a S-nitrosylation-mediated mechanism in porcine aortic valve interstitial cells (pAVICs) and single cell RNA-seq demonstrated regulation of NOTCH pathway by NO. A unbiased proteomic approach to identify S-nitrosylated proteins in valve cells found enrichment of the ubiquitin proteasome pathway and implicated S-nitrosylation of USP9X in NOTCH regulation during calcification. Furthermore, S-nitrosylated USP9X was shown to deubiquitinate and stabilize MIB1 for NOTCH1 activation. Consistent with this, genetic deletion ofUsp9xin mice demonstrated aortic valve disease and human calcified aortic valves displayed reduced S-nitrosylation of USP9X. These results demonstrate a novel mechanism by which S-nitrosylation dependent regulation of ubiquitin-associated pathway prevents CAVD.
Human ORC/MCM density is low in active genes and correlates with replication time but does not solely define replication initiation zones
Authors: Kirstein Nina , Buschle Alexander , Wu Xia , Krebs Stefan , Blum Helmut , Hammerschmidt Wolfgang , Lacroix Laurent , Hyrien Olivier , Audit Benjamin , Schepers Aloys 
Published: August 2020

AbstractEukaryotic DNA replication initiates during S phase from origins that have been licensed in the preceding G1 phase. Here, we compare ChIP-seq profiles of the licensing factors Orc2, Orc3, Mcm3, and Mcm7 with gene expression, replication timing and fork directionality profiles obtained by RNA-seq, Repli-seq and OK-seq. ORC and MCM are strongly and homogeneously depleted from transcribed genes, enriched at gene promoters, and more abundant in early-than in late-replicating domains. Surprisingly, after controlling these variables, no difference in ORC/MCM density is detected between initiation zones, termination zones, unidirectionally replicating and randomly replicating regions. Therefore, ORC/MCM density correlates with replication timing but does not solely regulate the probability of replication initiation. Interestingly, H4K20me3, a histone modification proposed to facilitate late origin licensing, was enriched in late replicating initiation zones and gene deserts of stochastic replication fork direction. We discuss potential mechanisms that specify when and where replication initiates in human cells.
A maternal effect regulates global DNA methylation patterns
Authors: Loos Remco , Carola Valeria , Audero Enrica , Brini Elena , Iacono Luisa Lo , Moles Anna , Bertone Paul , Gross Cornelius 
Published: August 2020

AbstractVariation in DNA methylation between individuals has been shown to be influenced by both genetic and environmental factors. However, the relative impact of genetic and non-genetic factors on DNA methylation patterns across the mammalian genome has not been systematically studied. We performed whole-genome methylation analysis in two inbred mouse strains, revealing striking differences in the global distribution of DNA methylation. Although global methylation patterns were indistinguishable for most genomic features, a significant increase in the number of unmethylated CpG-island promoters and first exons was observed between strains. Experiments using F1 reciprocal hybrid strains demonstrated that the genotype of the mother dictated global DNA methylation patterns. Cross-fostering experiments ruled out a postnatal maternal effect on these differences and suggested that they were driven by a prenatal maternal effect, possibly via differential deposition of maternal gene products into the oocyte or uterine environment. These data demonstrate that maternal effects have a major impact on global DNA methylation patterns.
Asymmetric histone inheritance regulates stem cell fate inDrosophilamidgut
Authors: Zion Emily , Chen Xin 
Published: August 2020

AbstractA fundamental question in developmental biology is how distinct cell fates are established and maintained through epigenetic mechanisms in multicellular organisms. Here, we report that preexisting (old) and newly synthesized (new) histones H3 and H4 are asymmetrically inherited by the distinct daughter cells during asymmetric division ofDrosophilaintestinal stem cells (ISCs). By contrast, in symmetrically dividing ISCs that produce two self-renewed stem cells, old and new H3 and H4 show symmetric inheritance patterns. These results indicate that asymmetric histone inheritance is tightly associated with the distinct daughter cell fates. To further understand the biological significance of this asymmetry, we express a mutant histone that compromises asymmetric histone inheritance pattern. We find increased symmetric ISC division and ISC tumors during aging under this condition. Together, our results demonstrate that asymmetric histone inheritance is important for establishing distinct cell identities in a somatic stem cell lineage, consistent with previous findings in asymmetrically dividing male germline stem cells inDrosophila. Therefore, this work sheds light on the principles of histone inheritance in regulating stem cell fatein vivo.
Airborne point counts: a method for estimating songbird abundance with drones
Authors: Somers McKenzie D. , Glass Darren B. , Immordino Marisa A. , Ozoh Precious S. , Sherman Lauren B. , Wilson Andrew M. 
Published: August 2020

AbstractUsing drones to conduct airborne bioacoustic surveys is a potentially useful new way to estimate the abundance of vocal bird species. Here we show that by using two recording devices suspended from a quadcopter drone it is possible to estimate distances to birds with precision. In an experimental test, the mean error of our estimated distances to a broadcast song across 11 points between 0 and 100 m away was just 3.47 m. In field tests we compared 1-minute airborne counts with 5-minute terrestrial counts at 34 count locations. We found that the airborne counts yielded similar data to the terrestrial point counts for most of the 10 the songbirds included in our analysis, and that the effective detection radii were also similar. However, airborne counts significantly under-detected the Northern Cardinal (χ29= 22.8, post-hoc testP= 0.007), which we attribute to a behavioral response to the drone. Airborne counts work best for species that vocalize close to the ground and have high frequency-range songs. Under those circumstances, airborne bioacoustics could have several advantages over ground-based surveys, including increased precision, increased repeatability, and easier access in difficult terrain. Further, we show that it is possible to do rapid surveys using airborne techniques, which could lead to the development of much more efficient survey protocols than are possible using traditional survey techniques.Lay SummaryWe show that it is possible to estimate the distance of singing birds from a drone, which then allows bird counts to be converted to true abundance or population densities.Using drones to count birds allows researchers to survey areas that may be difficult or dangerous to access on foot.Airborne counts are potentially a highly efficient and highly repeatable way to estimate populations of vocal bird species.
Hearing loss in Alzheimer Disease is associated with altered serum lipidomic biomarker profiles
Authors: Llano Daniel A. , Issa Lina K. , Devanarayan Priya , Devanarayan Viswanath ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: August 2020

AbstractRecent data have found that aging-related hearing loss (ARHL) is associated with the development of Alzheimer Disease (AD). However, the nature of the relationship between these two disorders is not clear. There are multiple potential factors that link ARHL and AD, and previous investigators have speculated that shared metabolic dysregulation may underlie the propensity to develop both disorders. Here, we investigate the distribution of serum lipidomic biomarkers in AD subjects with or without hearing loss in a publicly available dataset. Serum levels of 349 known lipids from 16 lipid classes were measured in 185 AD patients. Using previously defined co-regulated sets of lipids, both age- and sex-adjusted, we found that lipid sets enriched in phosphatidylcholine and phosphatidylethanolamine showed a strong inverse association with hearing loss. Examination of biochemical classes confirmed these relationships and revealed that serum phosphatidylcholine levels were significantly lower in AD subjects with hearing loss. A similar relationship was not found in normal subjects. These data suggest that a synergistic relationship may exist between AD, hearing loss and metabolic biomarkers, such that in the context of a pathological state such as AD, alterations in serum metabolic profiles are associated with hearing loss. These data also point to a potential role for phosphatidylcholine, a molecule with antioxidant properties, in the underlying pathophysiology of ARHL in the context of AD, which has implications for our understanding and potential treatment of both disorders.