bluuebunny/crossref_metadata_2025_split huggingface dataset:
Steady-state measures of visual suppression
Authors: Baker Daniel H. , Vilidaite Greta , Wade Alex R. 
Published: July 2021

AbstractIn the early visual system, suppression occurs between neurons representing different stimulus properties. This includes features such as orientation (cross-orientation suppression), eye-of-origin (interocular suppression) and spatial location (surround suppression), which are thought to involve distinct anatomical pathways. We asked if these separate routes to suppression can be differentiated by their pattern of gain control on the contrast response function measured in human participants using steady-state electroencephalography. Changes in contrast gain shift the contrast response function laterally, whereas changes in response gain scale the function vertically. We used a Bayesian hierarchical model to summarise the evidence for each type of gain control. A computational meta-analysis of 16 previous studies found the most evidence for contrast gain effects with overlaid masks, but no clear evidence favouring either response gain or contrast gain for other mask types. We then conducted two new experiments, comparing suppression from four mask types (monocular and dichoptic overlay masks, and aligned and orthogonal surround masks) on responses to sine wave grating patches flickering at 5Hz. At the occipital pole, there was strong evidence for contrast gain effects in all four mask types at the first harmonic frequency (5Hz). Suppression generally became stronger at more lateral electrode sites, but there was little evidence of response gain effects. At the second harmonic frequency (10Hz) suppression was stronger overall, and involved both contrast and response gain effects. Although suppression from different mask types involves distinct anatomical pathways, gain control processes appear to serve a common purpose, which we suggest might be to suppress less reliable inputs.
One year later: longitudinal effects of flexible school start times on teenage sleep and subjective psychological outcomes
Authors: Biller Anna M. , Molenda Carmen , Zerbini Giulia , Roenneberg Till , Winnebeck Eva C. 
Published: July 2021

AbstractEarly school times fundamentally clash with the late sleep of teenagers. This mismatch results in chronic sleep deprivation, which poses acute and long-term health risks and impairs students’ learning. Despite conclusive evidence that delaying school times has immediate benefits for sleep, the long-term effects on sleep are unresolved due to a shortage of longitudinal data. Here, we studied whether a flexible school start system, with the daily choice of an 8AM or 08:50AM-start, allowed secondary school students to improve their sleep and psychological functioning in a longitudinal pre-post design over exactly 1 year. Based on 2 waves, each with 6-9 weeks of daily sleep diary, we found that students maintained their 1-hour-sleep gain on days with later starts, both longitudinally (n=28) and cross-sectionally (n=79). This sleep gain was independent of chronotype and frequency of later starts but differed between genders. Girls were more successful in keeping early sleep onsets despite later sleep offsets, whereas boys delayed their onsets and thus had reduced sleep gains after 1 year. Students also reported psychological benefits (n=93), increased sleep quality and reduced alarm-driven waking on later school days. Despite these benefits on later schooldays, overall sleep duration was not extended in the flexible system. This was likely due to the persistently low uptake of the late-start option. If uptake can be further promoted, the flexible system is an appealing alternative to a fixed delay of school starts owing to possible circadian advantages (speculatively through prevention of phase-delays) and psychological mechanisms (e.g. sense of control).Significance statementTeenage sleep becomes progressively later during adolescence but school starts do not accommodate this shifted sleep window. This mismatch results in chronic sleep deprivation in teenagers worldwide, which is a pervasive public health concern. Delaying school starts could counteract this misalignment if students keep sleep onsets stable. However, few studies have investigated long-term effects of delayed starts on sleep. We observed here that students slept persistently longer and better when school started later in a flexible start system. Girls were especially successful in keeping stable onsets. Students also benefitted psychologically and liked the flexible system despite only a modest uptake of later starts. The flexible system is an interesting alternative to a fixed delay and should receive more scientific attention.
A Novel, Improved, Application for the Normalization of RNA-seq Expression Data in Complex Polyploids
Authors: Evans Dyfed Lloyd 
Published: July 2021

AbstractMuch of the work on the normalization of RNA-seq data has been performed on human, notably cancer tissue. Little work has been done in plants, particularly polyploids and those species with incomplete or no genomes. We present a novel implementation of GeTMM (Gene Length Corrected TMM) that accounts for GC bias and works at the transcript level. The algorithm also employs transcript length as a factor, allowing for incomplete transcripts and alternate transcripts. This significantly improves overall normalization. The GCGeTMM methodology also allows for simultaneous determination of differentially expressed transcripts (and by extension genes) and stably expressed genes to act as references for qRT-PCR and microarray analyses.
Structural basis of Ty3 retrotransposon integration at RNA Polymerase III-transcribed genes
Authors: Abascal-Palacios Guillermo , Jochem Laura , Pla-Prats Carlos , Beuron Fabienne , Vannini Alessandro 
Published: July 2021

ABSTRACTRetrotransposons are endogenous elements that have the ability to mobilise their DNA and integrate at different locations in the host genome. In budding yeast, the Ty3 retrotransposon integrates with an exquisite specificity in a narrow window upstream of RNA Polymerase III-transcribed genes, such as the genes of transfer RNAs, representing a paradigm for specific targeted integration.Here we present the cryo-EM reconstruction at 4.0 Å-resolution of an active Ty3 strand-transfer complex (Ty3 intasome) caught in the act of integrating onto a specific tRNA gene bound to the RNA Polymerase III general transcription factor TFIIIB, which is required for Ty3 specific targeting.The structure unravels the molecular mechanisms underlying Ty3 integration specificity at RNA Polymerase III-transcribed genes and sheds light into the architecture of a retrotransposon integration machinery during the process of strand transfer at a genomic locus. The Ty3 intasome establishes contacts with a region of the TATA-binding protein (TBP), a subunit of TFIIIB, which is blocked by the ubiquitous transcription regulator negative cofactor 2 (NC2) in RNA Pol II-transcribed genes.A previously unrecognised chromodomain of the Ty3 integrase mediates non- canonical interactions with TFIIIB and the tRNA gene itself, defining with extreme precision the position of the integration site. Surprisingly, Ty3 retrotransposon tethering to TFIIIB topologically resembles LEDGF/p75 transcription factor targeting by HIV retrovirus, highlighting mechanisms of convergent evolution by unrelated mobile elements and host organisms.The Ty3 intasome-TFIIIB-tRNA promoter complex presented here represents a detailed molecular snapshot of a general transcription factor’s co-option by a mobile element, resulting in harmless integration into the host genome.
Can fMRI functional connectivity index dynamic neural communication?
Authors: Martínez Sonsoles Alonso , Llera Alberto , Horst Gert ter , Vidaurre Diego 
Published: July 2021

AbstractIn order to continuously respond to a changing environment and support self-generating cognition and behaviour, neural communication must be highly flexible and dynamic at the same time than hierarchically organized. While whole-brain fMRI measures have revealed robust yet changing patterns of statistical dependencies between regions, it is not clear whether these statistical patterns —referred to as functional connectivity— can reflect dynamic large-scale communication in a way that is relevant to human cognition. For functional connectivity to reflect cognition, and therefore actual communication, we propose three necessary conditions: it must span sufficient temporal complexity to support the needs of cognition while still being highly organized so that the system behaves reliably; it must be able to adapt to the current behavioural context; it must exhibit fluctuations at timescales that are compatible with the timescales of cognition. To obtain reliable estimations of time-varying functional connectivity, we developed principal components of connectivity analysis (PCCA), an approach based on applying principal component analysis on multiple runs of a time-varying functional connectivity model. We use PCCA to show that functional connectivity follows low-yet multi-dimensional trajectories that can be reliably measured, and that these trajectories meet the aforementioned criteria. These analyses suggest that these trajectories might index certain aspects of communication between neural populations and support moment-to-moment cognition.Significance StatementfMRI functional connectivity is one of the most widely used metrics in neuroimaging research in both theoretical research and clinical applications. However, this work suffers from a lack of context because we still do not fully understand what fMRI functional connectivity can or cannot reflect biologically and behaviourally. In particular, can it reflect between-region neuronal communication? We develop methods to reliably quantify temporal trajectories of functional connectivity and investigate the nature of these trajectories across different experimental conditions. Using these methods, we demonstrate that functional connectivity exhibits reliable changes that are context-dependent, reflect cognitive complexity, and bear a relationship with cognitive abilities. These conditions show that fMRI functional connectivity could reflect changes in between-region communication above and beyond non-neural factors.
Orthogonal but linked neural codes for value
Authors: Maisson David J-N. , Fine Justin M. , Yoo Seng Bum Michael , Cash-Padgett Tyler V. , Wang Maya Zhe , Sleezer Brianna J. , Zimmermann Jan , Hayden Benjamin Y. 
Published: July 2021

ABSTRACTOur ability to effectively choose between dissimilar options implies that information regarding the options’ values must be available, either explicitly or implicitly, in the brain. Explicit realizations of value involve single neurons whose responses depend on value and not on the specific features that determine it. Implicit realizations, by contrast, come from the coordinated action of neurons that encode specific features. One signature of implicit value coding is that population responses to offers with the same value but different features should occupy semi- or fully orthogonal neural subspaces that are nonetheless linked. Here, we examined responses of neurons in six core value-coding areas in a choice task with risky and safe options. Using stricter criteria than some past studies have used, we find, surprisingly, no evidence for abstract value neurons (i.e., neurons with the response to equally valued risky and safe options) in any of these regions. Moreover, population codes for value resided in orthogonal subspaces; these subspaces were linked through a linear transform of each of their constituent subspaces. These results suggest that in all six regions, populations of neurons embed value implicitly in a distributed population.
Executable Network of SARS-CoV-2-Host Interaction Predicts Drug Combination Treatments
Authors: Howell Rowan , Clarke Matthew A. , Reuschl Ann-Kathrin , Chen Tianyi , Abbott-Imboden Sean , Singer Mervyn , Lowe David M. , Bennett Clare L. , Chain Benjamin , Jolly Clare , Fisher Jasmin 
Published: July 2021

AbstractThe COVID-19 pandemic has pushed healthcare systems globally to a breaking point. The urgent need for effective and affordable COVID-19 treatments calls for repurposing combinations of approved drugs. The challenge is to identify which combinations are likely to be most effective and at what stages of the disease. Here, we present the first disease-stage executable signalling network model of SARS-CoV-2-host interactions used to predict effective repurposed drug combinations for treating early- and late-stage severe disease. Using our executable model, we performed in silico screening of 9870 pairs of 140 potential targets and have identified 12 new drug combinations. Camostat and Apilimod were predicted to be the most promising combination in effectively supressing viral replication in the early stages of severe disease and were validated experimentally in human Caco-2 cells. Our study further demonstrates the power of executable mechanistic modelling to enable rapid pre-clinical evaluation of combination therapies tailored to disease progression. It also presents a novel resource and expandable model system that can respond to further needs in the pandemic.
A phospho-switch at Acinus-Serine437 controls autophagic responses to Cadmium exposure and neurodegenerative stress
Authors: Nandi Nilay , Zaidi Zuhair , Tracy Charles , Krämer Helmut 
Published: July 2021

SummaryNeuronal health depends on quality control functions of autophagy, but mechanisms regulating neuronal autophagy are poorly understood. Previously, we showed that in Drosophila starvation-independent quality control autophagy is regulated by Acinus and the Cdk5-dependent phosphorylation of its serine437 (Nandi et al., 2017). Here, we identify the phosphatase that counterbalances this activity and provides for the dynamic nature of Acinus-S437 phosphorylation. A genetic screen identified six phosphatases that genetically interacted with an Acinus gain-of-function model. Among these, loss of function of only one, the PPM-type phosphatase Nil (CG6036), enhanced pS437-Acinus levels. Cdk5-dependent phosphorylation of Acinus serine437 in nil1 animals elevates neuronal autophagy and reduces the accumulation of polyQ proteins in a Drosophila Huntington’s disease model. Consistent with previous findings that Cd2+ inhibits PPM-type phosphatases, Cd2+-exposure elevated Acinus-serine437 phosphorylation which was necessary for increased neuronal autophagy and protection against Cd2+-induced cytotoxicity. Together, our data establish the Acinus- S437 phospho-switch as critical integrator of multiple stress signals regulating neuronal autophagy.
Endorsement and Phylogenetic Analysis of some Fabaceae Plants based on DNA Barcoding gene MatK
Authors: Abdelsalam Nader R. , Hasan Mohamed E. , Rabie Samar M.A. , El-wakeel Houssam El-Din M.F. , Zaitoun Amera F. , Ghareeb Rehab Y. , Abdelsalam Aly Z. , Aly Hesham M. , Ibrahim Amira A. , Hemeida Alaa A. 
Published: July 2021

AbstractDNA barcodes have been considered as a tool to facilitate species identification based on their simplicity and high-level accuracy compression to the complexity and subjective biases linked to morphological identification of taxa. MaturaseK gene “MatK” of the chloroplast is very crucial in the plant system which is involved in the group II intron splicing. The main objective of this current study is determining the relative utility of the “MatK” chloroplast gene for barcoding in fifteen legume trees by both single region and multiregional approaches. The chloroplast “MatK” gene sequences were submitted to GenBank and accession numbers (GenBank: LC602060, LC602154, LC602263, LC603347, LC603655, LC603845, LC603846, LC603847, LC604717, LC604718, LC605994, LC604799, LC605995, LC606468, LC606469) were obtained with sequence length ranging from 730 to 1545 nucleotides. These DNA sequences were aligned with database sequence using PROMALS server, Clustal Omega server and Bioedit program. Also, the maximum likelihood and neighbor-joining algorithms for phylogenetic reconstruction using the MEGA-X program were employed. Overall, these results indicated that the phylogenetic tree analysis and the evolutionary distances of an individual dataset of each species were agreed with a phylogenetic tree of all each other consisting of two clades, the first clade comprising (Enterolobium contortisiliquum, Albizia lebbek), Acacia saligna, Leucaena leucocephala, Dichrostachys Cinerea, (Delonix regia, Parkinsonia aculeata), (Senna surattensis, Cassia fistula, Cassia javanica) and Schotia brachypetala were more closely to each other, respectively. The remaining four species of Erythrina humeana, (Sophora secundiflora, Dalbergia Sissoo, Tipuana Tipu) constituted the second clade. Therefore, MatK gene is considered promising a candidate for DNA barcoding in plant family Fabaceae and providing a clear relationship between the families. Moreover, their sequences could be successfully utilized in single nucleotide polymorphism (SNP) or part of the sequence as DNA fragment analysis utilizing polymerase chain reaction (PCR) in plant systematic.
Targeted Protein Acetylation in Cells Using Heterobifunctional Molecules
Authors: Wang Wesley W. , Chen Li-Yun , Wozniak Jacob M. , Jadhav Appaso M. , Anderson Hayden , Malone Taylor E. , Parker Christopher G. 
Published: July 2021

ABSTRACTProtein acetylation is a central event in orchestrating diverse cellular processes. However, current strategies to investigate protein acetylation in cells are often non-specific or lack temporal and magnitude control. Here, we developed an acetylation tagging system, AceTAG, to induce acetylation of targeted proteins. The AceTAG system utilizes bifunctional molecules to direct the lysine acetyltransferase p300/CBP to proteins fused with the small protein tag FKBP12F36V, resulting in their induced acetylation. Using AceTAG, we induced targeted acetylation of a diverse array of proteins in cells, specifically histone H3.3, the NF-κB subunit p65/RelA, and the tumor suppressor p53. We demonstrate that targeted acetylation with the AceTAG system is rapid, selective, reversible, and can be controlled in a dose-dependent fashion. AceTAG represents a useful strategy to modulate protein acetylation and will enable the exploration of targeted acetylation in basic biological and therapeutic contexts.Abstract Figure
Automated slice-specific z-shimming for fMRI of the human spinal cord
Authors: Kaptan Merve , Vannesjo S. Johanna , Mildner Toralf , Horn Ulrike , Hartley-Davies Ronald , Oliva Valeria , Brooks Jonathan C.W. , Weiskopf Nikolaus , Finsterbusch Jürgen , Eippert Falk 
Published: July 2021

AbstractFunctional magnetic resonance imaging (fMRI) of the human spinal cord faces many challenges, such as signal loss due to local magnetic field inhomogeneities. This issue can be addressed with slice-specific z-shimming, which compensates for the dephasing effect of the inhomogeneities using a slice-specific gradient pulse. Here, we aim to address outstanding issues regarding this technique by evaluating its effects on several aspects that are directly relevant for spinal fMRI and by developing two automated procedures in order to improve upon the time-consuming and subjective nature of manual selection of z-shims: one procedure finds the z-shim that maximizes signal intensity in each slice of an EPI reference-scan and the other finds the through-slice field inhomogeneity for each EPI-slice in field map data and calculates the required compensation gradient moment. We demonstrate that the beneficial effects of z-shimming are apparent across different echo times, hold true for both the dorsal and ventral horn, and are also apparent in the temporal signal-to-noise ratio (tSNR) of EPI time-series data. Both of our automated approaches were faster than the manual approach, lead to significant improvements in gray matter tSNR compared to no z-shimming and resulted in beneficial effects that were stable across time. While the field-map-based approach performed slightly worse than the manual approach, the EPI-based approach performed as well as the manual one and was furthermore validated on an external corticospinal data-set (N>100). Together, automated z-shimming may improve the data quality of future spinal fMRI studies and lead to increased reproducibility in longitudinal studies.
DectiSomes: Glycan Targeting of Liposomal Drugs Improves the Treatment of Disseminated Candidiasis
Authors: Ambati Suresh , Phan Tuyetnhu , Lewis Zachary A. , Lin Xiaorong , Meagher Richard B. 
Published: July 2021

ABSTRACTCandida albicans causes life-threatening disseminated candidiasis. Individuals at greatest risk have weakened immune systems. An outer cell wall, exopolysaccharide matrix, and biofilm rich in oligoglucans and oligomannans help Candida spp. evade host defenses. Even after antifungal drug treatment the one-year mortality rate exceeds 25%. Undoubtedly there is room to improve antifungal drug performance. The mammalian C-type lectin pathogen receptors Dectin-1 and Dectin-2 bind to fungal oligoglucans and oligomannans, respectively. We previously coated amphotericin B-loaded liposomes, AmB-LLs, pegylated analogs of AmBisome, with the ligand binding domains of these two Dectins. DectiSomes, DEC1-AmB-LLs and DEC2-AmB-LLs, showed two distinct patterns of binding to the exopolysaccharide matrix surrounding C. albicans hyphae grown in vitro, while untargeted AmB-LLs did not bind. DectiSomes were preferentially associated with fungal colonies in the kidneys. In a neutropenic mouse model of candidiasis, DEC1-AmB-LLs and DEC2-AmB-LLs delivering only one dose of 0.2 mg/kg AmB significantly reduced the kidney fungal burden several fold relative to AmB-LLs, based on either colony forming units (P= 0.013 to 8.8 × 10-5) or quantitative PCR of fungal rRNA ITS (P= 5.5×10-5 to 3.0×10-10). DEC1-AmB-LLs and DEC2-AmB-LLs significantly increased the percent of surviving mice relative to AmB-LLs. Dectin-2 targeted anidulafungin loaded liposomes and AmBisomes, DEC2-AFG-LLs and DEC2-AmBisome reduced fungal burden in the kidneys several fold over their untargeted counterparts (P=7.8×10-5 and 0.0020, respectively). The data herein suggest that targeting of a variety of antifungal drugs to fungal glycans may achieve lower safer effective doses and improve drug efficacy against a variety of invasive fungal infections.
Characterization of a Novel Plasmid in Serratia marcescens Harboring blaGES-5 Isolated from a Nosocomial Outbreak in Japan
Authors: Nakanishi Noriko , Komatsu Shoko , Iwamoto Tomotada , Nomoto Ryohei 
Published: July 2021

AbstractSerratia marcescens is a nosocomial pathogen with carbapenem resistance, limiting the availability of effective treatment options. In this study, we performed molecular characterization of GES-5 carbapenemase-producing S. marcescens isolated from an outbreak in Japan. Comparative genetic analysis revealed that the blaGES-5–encoding plasmid p2020-O-9 is a unique plasmid contributing towards carbapenem resistance. Furthermore, this study highlights the necessity of surveillance programs for monitoring novel, along with commonly occurring carbapenemases in clinical settings.