bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using kinematics to re-define the pull test as a quantitative biomarker of the postural response
Authors: Daly Samuel , Hanson Jacob T. , Mavanji Vibha , Gravely Amy , Lewis Scott , Ashe James , Looft John M. , McGovern Robert A. 
Published: May 2021

AbstractBackgroundQuantitative biomarkers are needed for the diagnosis, monitoring and therapeutic assessment of postural instability.ObjectiveCreate a practical and objective measure of postural instability using kinematic measurement of the pull test to incorporate into clinical practice.MethodsTwenty patients evaluated and treated for normal pressure hydrocephalus were tested over a number of sessions. Patients were fitted with 15 inertial measurement units during each session. At each session, the patient underwent 10-20 pull tests performed by a trained clinician. The clinician purposefully induced a range of perturbations during each session to assess the patient’s step response. Kinematic data was extracted for each pull test and aggregated.ResultsPatients participated in 57 sessions for a total of 860 trials and were separated into groups by pull test score. The center of mass velocity profile easily distinguished between groups such that score increases correlated with decreases in peak velocity and later peak velocity onset. All patients except those scored as “3” demonstrated an increase in step length and decrease in reaction time with increasing pull intensity. Groups were distinguished by differences in overall step length or reaction time regardless of pull intensity (y-intercept). A logistic regression model including only kinematic variables identified three kinematic factors that could be used to identify trials in which patients needed to be caught (i.e. “fell”).ConclusionAn instrumented, purposefully varied pull test produces kinematic metrics useful for distinguishing clinically meaningful differences between and within NPH patients. These metrics should be followed prospectively to examine fall risk.
Investigating the possible origin and transmission routes of SARS-CoV-2 genomes and variants of concern in Bangladesh
Authors: Nahid Abdullah Al , Ghosh Ajit 
Published: May 2021

AbstractThe COVID-19 pandemic induced by the SARS-CoV-2 virus and its variants has ravaged most countries around the world including Bangladesh. We have analyzed publicly available genomic data to understand the current COVID-19 outbreak scenario as well as the evolutionary origin and transmission routes of SARS-CoV-2 isolates in Bangladesh. All the early isolates as well as recent B.1.1.7 and B.1.351 variants had already spread across the major divisional cities of Bangladesh. A sex biasness towards male COVID-19 patient samples sequencing has observed over female in all age-group, that could be the trend in infection rate. Phylogenetic analysis indicated a total of 13 estimated countries, including Italy, India, United Kingdom, Saudi Arabia, United Arab Emirates, Germany, Australia, New Zealand, South Africa, Democratic Republic of the Congo, United States, Russia, and Denmark, could be the possible origin introduced SARS-CoV-2 isolates in Bangladesh due to regional and intercontinental travel. Recent, B.1.1.7 variant could be imported from a total of 7 estimated countries including UK, India, Nigeria, Spain, Ireland, Australia, and Indonesia, while South Africa and the United States are the most likely sources of B.1351 variant in Bangladesh. Based on these findings, public health strategies could be designed and implemented to reduce the local transmission of the virus.
Distinct changes in mature root and growing root tip proteomes underlie physiological responses of bread wheat to salinity stress
Authors: Dissanayake Bhagya M. , Staudinger Christiana , Munns Rana , Taylor Nicolas L. , Millar A. Harvey 
Published: May 2021

SummaryThe impact of salinity on wheat plants is often studied by analysis of shoot responses, even though the main mechanism of tolerance is shoot Na+ exclusion. There is a need to understand the molecular responses of root tissues that directly experience rising NaCl concentrations. We have combined analysis of root growth, ion content and respiration with proteome responses in wheat root tip and mature root tissues under saline conditions. We find significant changes in translation and protein synthesis, energy metabolism and amino acid metabolism in a root tissue specific manner. Translation and protein synthesis related proteins showed significant decreases in abundance only in root tips, as did most of the glycolytic enzymes and selected TCA cycle enzymes and ATP synthase subunits. This selective root tip proteome response indicates protein synthesis capacity and energy production were impaired under salt stress, correlating with the anatomical response of roots and reduced root tip respiration rate. Wheat roots respond directly to soil salinity, therefore shoot responses such as reduction in shoot growth and photosynthetic capacity need to be considered in light of these effects.
Undivided attention: The temporal effects of attention dissociated from decision, memory, and expectation
Authors: Moerel Denise , Grootswagers Tijl , Robinson Amanda K. , Shatek Sophia M. , Woolgar Alexandra , Carlson Thomas A. , Rich Anina N. 
Published: May 2021

AbstractSelective attention prioritises relevant information amongst competing sensory input. Time-resolved electrophysiological studies have shown stronger representation of attended compared to unattended stimuli, which has been interpreted as an effect of attention on information coding. However, because attention is often manipulated by making only the attended stimulus a target to be remembered and/or responded to, many reported attention effects have been confounded with target-related processes such as visual short-term memory or decision-making. In addition, the effects of attention could be influenced by temporal expectation. The aim of this study was to investigate the dynamic effect of attention on visual processing using multivariate pattern analysis of electroencephalography (EEG) data, while 1) controlling for target-related confounds, and 2) directly investigating the influence of temporal expectation. Participants viewed rapid sequences of overlaid oriented grating pairs at fixation while detecting a “target” grating of a particular orientation. We manipulated attention, one grating was attended and the other ignored, and temporal expectation, with stimulus onset timing either predictable or not. We controlled for target-related processing confounds by only analysing non-target trials. Both attended and ignored gratings were initially coded equally in the pattern of responses across EEG sensors. An effect of attention, with preferential coding of the attended stimulus, emerged approximately 230ms after stimulus onset. This attention effect occurred even when controlling for target-related processing confounds, and regardless of stimulus onset predictability. These results provide insight into the effect of attention on the dynamic processing of competing visual information, presented at the same time and location.
The mechanism underlying the organization of Borna disease virus inclusion bodies is unique among mononegaviruses
Authors: Hirai Yuya , Tomonaga Keizo , Horie Masayuki 
Published: May 2021

AbstractInclusion bodies (IBs) are characteristic biomolecular condensates organized by mononegaviruses. Here, we characterize the IBs of Borna disease virus 1 (BoDV-1), a unique mononegavirus that forms IBs in the nucleus, in terms of liquid-liquid phase separation (LLPS). The BoDV-1 phosphoprotein (P) alone induces LLPS and the nucleoprotein (N) is incorporated into the P droplet in vitro. In contrast, co-expression of N and P is required for the formation of IB-like structure in cells. Furthermore, while BoDV-1 P binds to RNA, an excess amount of RNA dissolves the liquid droplets formed by N and P. Notably, the N-terminal intrinsically disordered region of BoDV-1 P is essential to drive LLPS and bind to RNA, suggesting that both abilities could compete with one another. These features are unique among mononegaviruses, and thus this study will contribute to a deeper understanding of LLPS-driven organization and RNA-mediated regulation of biomolecular condensates.
Systemic gene therapy with thymosin β4 alleviates glomerular injury in mice
Authors: Mason William J , Jafree Daniyal J , Pomeranz Gideon , Kolatsi-Joannou Maria , Pacheco Sabrina , Moulding Dale A , Wolf Anja , Kupatt Christian , Peppiatt-Wildman Claire , Papakrivopoulou Eugenia , Riley Paul R , Long David A , Vasilopoulou Elisavet 
Published: May 2021

AbstractPlasma ultrafiltration in the kidney occurs across glomerular capillaries, which are surrounded by epithelial cells called podocytes. Podocytes have a unique shape maintained by a complex cytoskeleton, which becomes disrupted in glomerular disease resulting in defective filtration and albuminuria. Lack of endogenous thymosin β4 (TB4), an actin sequestering peptide, exacerbates glomerular injury and disrupts the organisation of the podocyte actin cytoskeleton, however, the effect of exogenous TB4 therapy on podocytopathy is unknown. Here, through interrogating single-cell RNA-sequencing data of isolated glomeruli we demonstrate that Adriamycin, a toxin which injures podocytes and leads to leakage of albumin in the urine of mice, results in reduced levels of podocyte TB4. Systemic administration of an adeno-associated virus vector encoding TB4 prevented Adriamycin-induced podocyte loss and albuminuria. Adriamycin injury was associated with disorganisation of the actin cytoskeleton in vitro, which was ameliorated by exogenous TB4. Furthermore, Adriamycin administration in mice was associated with increased prevalence of podocyte vesicles, a mechanism by which albumin may leak into the urine, which was also prevented by TB4. Collectively, we propose that TB4 gene therapy prevents podocyte injury and maintains glomerular filtration via modulation of the podocyte cytoskeleton thus presenting a novel treatment strategy for glomerular disease.
Standard Sample Storage Conditions Impact on Inferred Microbiome Composition and Antimicrobial Resistance Patterns
Authors: Poulsen Casper Sahl , Kaas Rolf Sommer , Aarestrup Frank M. , Pamp Sünje Johanna 
Published: May 2021

AbstractStorage of biological specimens is crucial in the life and medical sciences. The storage conditions for samples can be different for a number of reasons, and it is unclear which effect this can have on the inferred microbiome composition in metagenomics analyses. Here, we assess the effect of common storage temperatures (deep freezer: -80°C, freezer: -20°C, fridge: 5°C, room temperature: 22°C) and storage times, (immediate sample processing: 0h, next day: 16h, over weekend: 64h, and longer term: 4, 8, 12 months), as well as repeated sample freezing and thawing (2-4 freeze-thaw cycles). We examine two different pig feces and sewage samples, unspiked and spiked with a mock community, and in triplicates, respectively, amounting to a total of 438 samples (777 Gbp; 5.1 billion reads). Storage conditions had a significant and systematic effect on the taxonomic and functional composition of microbiomes. Distinct microbial taxa and antimicrobial resistance classes were in some situations similarly effected across samples, while others were not, suggesting an impact of individual inherent sample characteristics. With an increasing number of freeze-thaw cycles, an increasing abundance of Firmicutes, Actinobacteria, and eukaryotic microorganisms was observed. We include recommendations for sample storage, and strongly suggest including more detailed information in the metadata together with the DNA sequencing data in public repositories to better facilitate meta-analyses and reproducibility of findings.IMPORTANCEPrevious research has reported effects of DNA isolation, library preparation, and sequencing technology on metagenomics-based microbiome composition; however, the effect of biospecimen storage conditions has not been thoroughly assessed. We examined the effect of common sample storage conditions on metagenomics-based microbiome composition and find significant and, in part, systematic effects. Repeated freeze-thaw cycles could be used to improve the detection of microorganisms with more rigid cell walls, including parasites. We provide a dataset that could also be used for benchmarking algorithms to identify and correct for batch effects. Overall, the findings suggest that all samples of a microbiome study should be stored in the same way. Furthermore, there is a need to mandate more detailed information about sample storage and processing published together with the DNA sequencing data at INSDC (ENA/EBI, NCBI, DDBJ) or other repositories.
In vivo complex haploinsufficiency-based genetic analysis identifies a transcription factor circuit regulating Candida albicans oropharyngeal infection and epithelial cell endocytosis
Authors: Solis Norma V. , Wakade Rohan S. , Ollinger Tomye L. , Wellington Melanie , Mitchell Aaron P. , Filler Scott G. , Krysan Damian J. 
Published: May 2021

AbstractOropharyngeal candidiasis (OPC) is a common infection that complicates a wide range of medical conditions which can cause either mild or severe disease depending on the patient. The pathobiology of OPC shares many features with candidal biofilms of abiotic surfaces. The transcriptional regulation of C. albicans formation of biofilms on abiotic surfaces has been extensively characterized and involves six key transcription factors (Efg1, Ndt80, Rob1, Bcr1, Brg1, and Tec1). To determine whether this same in vitro biofilm transcriptional regulatory network played a role in OPC, we have carried out the first systematic genetic interaction analysis in a mouse model of C. albicans infection. Whereas all six transcription factors are required for in vitro biofilm formation, only three homozygous deletion mutants (tec1ΔΔ, bcr1ΔΔ, and rob1ΔΔ) and one heterozygous mutant (tec1Δ/TEC1) have reduced infectivity in a mouse model of OPC, indicating the network is more robust in vivo than in vitro. Although single mutants (heterozygous or homozygous) of BRG1 and EFG1 have no effect on fungal burden, the double heterozygous and homozygous mutants have dramatically reduced infectivity, indicating a critical genetic interaction between these two transcription factors. Using epistasis analysis, we have formulated a genetic circuit [EFG1+BRG1]→TEC1→BCR1 that is required for OPC infectivity and oral epithelial cell endocytosis. Surprisingly, we also found transcription factor mutants with in vitro defects in filamentation such as efg1ΔΔ and brg1ΔΔ filament during oral infection and that decreased filamentation did not correlate with decreased infectivity. Taken together, these data indicate that key in vitro biofilm transcription factors are involved in OPC but that the network characteristics and functional connections are remodeled significantly during interactions with tissues.Author SummaryThe pathology of oral candidiasis has features of biofilm formation, a well-studied process in vitro. Based on that analogy, we hypothesized that network of transcription factors that regulates in vitro biofilm formation might have similarities and differences in during oral infection. To test this, we employed the first systematic genetic interaction analysis of C. albicans in a mouse model of oropharyngeal infection. This revealed that the six regulators involved in in vitro biofilm formation played roles in vivo but that the functional connections between factors were quite distinct. Surprisingly, we also found that, while many of the factors are required for filamentation in vitro, none of the transcription factor deletion mutants was deficient for this key virulence trait in vivo. These observations clearly demonstrate that C. albicans regulates key aspects of its biology differently in vitro and in vivo.
Improved HIV-1 drug resistance mutation prediction using quasispecies reconstruction supported analysis
Authors: Sutar Jyoti , Bhowmick Shilpa , Padwal Varsha , Nagar Vidya , Patil Priya , Patel Vainav , Bandivdekar Atmaram 
Published: May 2021

AbstractAccurate and sensitive approaches to detect HIV-1 drug resistance mutations (DRMs) are indispensable for the paradigm of ‘treatment as prevention’. While HIV-1 proviral DNA allows sensitive high throughput sequencing (HTS)-based DRM detection, its applicability is limited by presence of defective genomes. This study demonstrates application of quasispecies reconstruction algorithms (QRAs) to improve DRM detection sensitivity from proviral DNA. A robust benchmarking of 5 QRAs was performed with 2 distinct experimental control-datasets including a stringent, novel control: DCPM, simulating in-vivo variant distribution (0.08%-86.5%). Selected QRA was further evaluated for its ability to differentiate DRMs from hypermutated sequences using an in-silico control. PredictHaplo outperformed all others in terms of precision and was selected for further analysis. Near full-genome HTS was performed on proviral DNA from 20 HIV-1C infected individuals, at different stages of ART, from Mumbai, India. DRM detection was performed through residue-wise variation analysis and implementation of QRAs. Both analyses were highly concordant for DRM frequencies >10% (spearman r=0.91, p<0.0001). Phylogenetic association in HTS datasets with shared transmission history could also be demonstrated by PredictHaplo. This study highlights utility of QRAs as an adjunct to traditional residue-wise variation-based DRM detection leading to optimal personalized ART as well as better disease management.
Rab3a regulates melanin exocytosis induced by keratinocyte-conditioned medium
Authors: Cabaço Luís C. , Bento-Lopes Liliana , Neto Matilde V. , Ramalho José S. , Seabra Miguel C. , Barral Duarte C. 
Published: May 2021

ABSTRACTSkin pigmentation relies on melanin and is crucial for photoprotection against ultraviolet radiation-induced toxicity. Melanin is synthesized and stored in melanosomes, within melanocytes and then transferred to keratinocytes. While the molecular players involved in melanogenesis have been extensively studied, those underlying melanin transfer remain poorly characterized. Previously, our group proposed that coupled exo/phagocytosis is the predominant mechanism of melanin transfer in human skin and showed an essential role for Rab11b and the exocyst tethering complex in this process. Using a fluorescence-based assay, we show here that keratinocyte-conditioned medium (KCM) specifically induces melanin exocytosis from melanocytes. Moreover, we found that Rab3a, but not Rab11b, regulates melanin exocytosis upon KCM stimulation. In fact, melanosomes accumulate in melanocyte dendrites upon KCM stimulation, co-localizing with Rab3a mainly in the vicinity of the plasma membrane. Additionally, Rab3a silencing does not affect melanin transfer in melanocyte/keratinocyte co-cultures, in contrast with Rab11b depletion, indicating that Rab11b regulates non-KCM-stimulated melanin exocytosis. Thus, our results suggest the existence of at least two distinct routes of melanin exocytosis: one controlled by Rab11b and another Rab3a-dependent, stimulated by KCM. Furthermore, these results provide evidence that soluble factors secreted by keratinocytes can control skin pigmentation via induction of melanocyte signaling pathways that promote peripheral transport of melanosomes and a Rab3a-mediated exocytosis mechanism.
ProteinBERT: A universal deep-learning model of protein sequence and function
Authors: Brandes Nadav , Ofer Dan , Peleg Yam , Rappoport Nadav , Linial Michal 
Published: May 2021

AbstractSelf-supervised deep language modeling has shown unprecedented success across natural language tasks, and has recently been repurposed to biological sequences. However, existing models and pretraining methods are designed and optimized for text analysis. We introduce ProteinBERT, a deep language model specifically designed for proteins. Our pretraining scheme consists of masked language modeling combined with a novel task of Gene Ontology (GO) annotation prediction. We introduce novel architectural elements that make the model highly efficient and flexible to very large sequence lengths. The architecture of ProteinBERT consists of both local and global representations, allowing end-to-end processing of these types of inputs and outputs. ProteinBERT obtains state-of-the-art performance on multiple benchmarks covering diverse protein properties (including protein structure, post translational modifications and biophysical attributes), despite using a far smaller model than competing deep-learning methods. Overall, ProteinBERT provides an efficient framework for rapidly training protein predictors, even with limited labeled data. Code and pretrained model weights are available at https://github.com/nadavbra/protein_bert.
Testing the maintenance of natural responses to survival-relevant calls in the conservation breeding population of a critically endangered corvid (Corvus hawaiiensis)
Authors: Sabol Anne C. , Greggor Alison L. , Masuda Bryce , Swaisgood Ronald R. 
Published: May 2021

AbstractVocal communication serves an important role in driving many animals’ social interactions and ultimately their survival. However, both the structure of and responses towards natural vocal behavior can be lost or subject to alteration under human care. Determining if animals in conservation breeding programs exhibit and respond appropriately to species-specific vocalizations is therefore important for ensuring their survival and persistence post-release. We tested whether endangered ‘alalā(Corvus hawaiiensis),which are extinct in nature, have retained their natural responses to vocal calls that were previously linked to survival and reproduction in the wild. We conducted our studies on breeding populations derived from a small number of founding ‘alalā maintained under human care since their extinction in the wild in 2002. We presented pairs of ‘alalā with alarm, territorial intrusion, and two types of control playback calls (a non-threatening territorial maintenance call and a novel heterospecific call). ‘Alalā were significantly more likely to approach the speaker following alarm call playback than other call types, and were more likely to respond to territorial intrusion calls with the same aggressive territorial calls. Males were more likely to make these aggressive calls than females, mirroring their roles in territory defense. We also found individual consistency in the level of vocal behavior response across all call types, indicating that some individuals are more vocal than others. These results are encouraging, showing that ‘alalā exhibit relevant, species-specific behaviors despite generations under human care. They do illustrate, however, that not all individuals respond appropriately, so animals’ responses to vocal stimuli may be an important factor to consider in determining the release suitability of individuals.Significance StatementEffective communication is crucial to the survival of many animals, but can erode without natural selection. Therefore, testing the flexibility and maintenance of communication and vocal responses in contexts where animals are isolated from conspecifics or from survival consequences, such as in conservation breeding centers, can help determine species’ susceptibility to communication loss. We used playbacks of survival-related conspecific calls to test if ‘alalā(Corvus hawaiiensis),retained species-specific responses to these calls after generations under human care. We found that birds maintained a species-level natural response, however these natural responses were not consistent across individuals, suggesting that some birds may not be well equipped to survive in the wild without additional training or care.