bluuebunny/crossref_metadata_2025 huggingface dataset:
Editorial: Scaling the Turbulence Edifice
Authors: Bec Jérémie , Krstulovic Giorgio , Matsumoto Takeshi , Ray Samriddhi Sankar , Vincenzi Dario
Published: January 2022

Turbulence is unique in its appeal across physics, mathematics and engineering. And yet a microscopic theory, starting from the basic equations of hydrodynamics, still eludes us. In the last decade or so, new directions at the interface of physics and mathematics have emerged, which strengthens the hope of ‘solving’ one of the oldest problems in the natural sciences. This two-part theme issue unites these new directions on a common platform emphasizing the underlying complementarity of the physicists’ and the mathematicians’ approaches to a remarkably challenging problem.

This article is part of the theme issue ‘Scaling the turbulence edifice (part 1)’.
regentrans: a framework and R package for using genomics to study regional pathogen transmission
Authors: Hoffman Sophie , Lapp Zena , Wang Joyce , Snitkin Evan S.
Published: January 2022

Increasing evidence of regional pathogen transmission networks highlights the importance of investigating the dissemination of multidrug-resistant organisms (MDROs) across a region to identify where transmission is occurring and how pathogens move across regions. We developed a framework for investigating MDRO regional transmission dynamics using whole-genome sequencing data and created regentrans, an easy-to-use, open source R package that implements these methods (https://github.com/Snitkin-Lab-Umich/regentrans). Using a dataset of over 400 carbapenem-resistant isolates of

Klebsiella pneumoniae

collected from patients in 21 long-term acute care hospitals over a one-year period, we demonstrate how to use our framework to gain insights into differences in inter- and intra-facility transmission across different facilities and over time. This framework and corresponding R package will allow investigators to better understand the origins and transmission patterns of MDROs, which is the first step in understanding how to stop transmission at the regional level.
FAMILY SUPPORT-BASED PSYCHOEDUCATION IN CARING SCHIZOPHRENIC PATIENTS: A LITERATURE REVIEW
Authors: Iswanti Dwi Indah , Rumambo Pandin Moses Glorino
Published: January 2022

Background

The burden of family in caring a schizophrenia impacts on psychological shock and emotional burden; lack of disease knowledge and care skills; poor patient medication adherence; the difficulty of getting along with patients; conflict in the family or at work; financial burden; and need adequate social support.

Aim

This study discussed how family support takes care of people with schizophrenia with a psychoeducational approach in mental health service settings.

Method

A non-systematic literature review was carried out using the PICO (Population, Intervention, Comparison, Outcome) framework utilizing Scopus, CINAHL, and ProQuest databases in the last 5 years, searching with keywords “Family Support AND Schizophrenia OR Family Psychoeducation”.

Results

Families with schizophrenia experience the most potent stressors on the burden of care borne, in addition to stigma and the frequency of relapse of sufferers. Community care providers can involve the family in various ways, such as providing psychoeducation, supporting the family’s physical, emotional and social needs, and behavioral family assessment or family therapy.

Conclusion

Mental health services must develop and imply family psychoeducation training.
Identifying the potential role of insomnia on multimorbidity: A Mendelian randomization phenome-wide association study in UK Biobank
Authors: Gibson Mark J , Lawlor Deborah A , Millard Louise AC
Published: January 2022

Objectives: To identify the breadth of potential causal effects of insomnia on health outcomes and hence its possible role in multimorbidity.
Design: Mendelian randomisation (MR) Phenome-wide association study (MR-PheWAS) with two-sample Mendelian randomisation follow-up.
Setting: Individual data from UK Biobank and summary data from a number of genome-wide association studies.
Participants: 336,975 unrelated white-British UK Biobank participants.
Exposures: Standardised genetic risk of insomnia for the MR-PheWAS and genetically predicted insomnia for the two-sample MR follow-up, with insomnia instrumented by a genetic risk score (GRS) created from 129 single-nucleotide polymorphisms (SNPs).
Main outcomes measures: 11,409 outcomes from UK Biobank extracted and processed by an automated pipeline (PHESANT). Potential causal effects (i.e., those passing a Bonferroni-corrected significance threshold) were followed up with two-sample MR in MR-Base, where possible.
Results: 437 potential causal effects of insomnia were observed for a number of traits, including anxiety, stress, depression, mania, addiction, pain, body composition, immune, respiratory, endocrine, dental, musculoskeletal, cardiovascular and reproductive traits, as well as socioeconomic and behavioural traits. We were able to undertake two-sample MR for 71 of these 437 and found evidence of causal effects (with directionally concordant effect estimates across all analyses) for 25 of these. These included, for example, risk of anxiety disorders (OR=1.55 [95% confidence interval (CI): 1.30, 1.86] per category increase in insomnia), diseases of the oesophagus/stomach/duodenum (OR=1.32 [95% CI: 1.14, 1.53]) and spondylosis (OR=1.57 [95% CI: 1.22, 2.01]).
Conclusion: Insomnia potentially causes a wide range of adverse health outcomes and behaviours. This has implications for developing interventions to prevent and treat a number of diseases in order to reduce multimorbidity and associated polypharmacy.
No One Is Leaving This Time: Appraisal of Awareness and Knowledge of Port Health Officers on International Health Regulation IHR (2005)
Authors: Adiama Yusuf Babatunde , Adewoye Solomon Olayinka , Olaniyi Opasola Afolabi , Lateefat Habeeb Modupe , Ahmed Abdullahi , Raimi Morufu Olalekan
Published: January 2022

Background

Historically, ships have played an important role in transmitting infectious diseases around the world. The spread of cholera pandemics in the 19th century was thought to be linked to trade routes and facilitated by merchant shipping. The international maritime traffic of people and goods has often contributed to the spread of pathogens affecting public health.

Objectives

To assess level of awareness and knowledge of international Health regulation (IHR 2005) content among port health officer

Methods

The study design was descriptive cross-sectional evaluation, questionnaires were used to capture the respondents’ knowledge, awareness and sanitary condition of ship in accordance with (IHR 2005)

Results

On awareness and knowledge, Majority of the respondent (77.1 %) demonstrate good awareness of the IHR (2005), while 22.9% had not and some even testified of hearing the said document for the first time. Despite the fact that majority of respondent were aware but only 24.6% of them can actually demonstrate good knowledge of IHR (2005) and its intent to protect and prevent spread of disease along the international route.

Conclusion

There is need to improve the knowledge of port health officers by expand training and guidance on application of the IHR’s to frontline officer at point of entries. Also ensure more thorough inspection and avoid influence of ship agent during inspection of ship.
CCPLS reveals cell-type-specific spatial dependence of transcriptomes in single cells
Authors: Tsuchiya Takaho , Hori Hiroki , Ozaki Haruka
Published: January 2022

Motivation

Cell-cell communications regulate internal cellular states, e.g., gene expression and cell functions, and play pivotal roles in normal development and disease states. Furthermore, single-cell RNA sequencing methods have revealed cell-to-cell expression variability of highly variable genes (HVGs), which is also crucial. Nevertheless, the regulation on cell-to-cell expression variability of HVGs via cell-cell communications is still largely unexplored. The recent advent of spatial transcriptome methods has linked gene expression profiles to the spatial context of single cells, which has provided opportunities to reveal those regulations. The existing computational methods extract genes with expression levels influenced by neighboring cell types. However, limitations remain in the quantitativeness and interpretability: they neither focus on HVGs nor consider the effects of multiple neighboring cell types.

Results

Here, we propose CCPLS (Cell-Cell communications analysis by Partial Least Square regression modeling), which is a statistical framework for identifying cell-cell communications as the effects of multiple neighboring cell types on cell-to-cell expression variability of HVGs, based on the spatial transcriptome data. For each cell type, CCPLS performs PLS regression modeling and reports coefficients as the quantitative index of the cell-cell communications. Evaluation using simulated data showed our method accurately estimated the effects of multiple neighboring cell types on HVGs. Furthermore, applications to the two real datasets demonstrate that CCPLS can extract biologically interpretable insights from the inferred cell-cell communications.

Availability

The R package is available athttps://github.com/bioinfo-tsukuba/CCPLS. The data are available athttps://github.com/bioinfo-tsukuba/CCPLS_paper.

Contact

haruka.ozaki@md.tsukuba.ac.jp

Supplementary information

Supplementary data are available at Bioinformatics online.
Assessing the clinical severity of the Omicron variant in the Western Cape Province, South Africa, using the diagnostic PCR proxy marker of RdRp target delay to distinguish between Omicron and Delta infections – a survival analysis
Authors: Hussey Hannah , Davies Mary-Ann , Heekes Alexa , Williamson Carolyn , Valley-Omar Ziyaad , Hardie Diana , Korsman Stephen , Doolabh Deelan , Preiser Wolfgang , Maponga Tongai , Iranzadeh Arash , Wasserman Sean , Boloko Linda , Symons Greg , Raubenheimer Peter , Viljoen Abraham , Parker Arifa , Schrueder Neshaad , Solomon Wesley , Rousseau Petro , Wolter Nicole , Jassat Waasila , Cohen Cheryl , Lessells Richard , Wilkinson Robert J , Boulle Andrew , Hsiao Nei-yuan
Published: January 2022

Background

Emerging data suggest that SARS-CoV-2 Omicron variant of concern (VOC)is associated with reduced risk of severe disease. The extent to which this reflects a difference in the inherent virulence of Omicron, or just higher levels of population immunity, is currently not clear.

Methods

RdRp target delay (RTD: a difference in cycle threshold value of RdRp - E > 3.5) in the Seegene Allplex™ 2019-nCoV PCR assay is a proxy marker for the Delta VOC. The absence of this proxy marker in the period of transition to Omicron was used to identify suspected Omicron VOC infections.

Cox regression was performed for the outcome of hospital admission in those who tested positive for SARS-CoV-2 on the Seegene Allplex™ assay from 1 November to 14 December 2021 in the Western Cape Province, South Africa, public sector. Vaccination status at time of diagnosis, as well as prior diagnosed infection and comorbidities, were adjusted for.

Results

150 cases with RTD (proxy for Delta) and 1486 cases without RTD (proxy for Omicron) were included. Cases without RTD had a lower hazard of admission (adjusted Hazard Ratio [aHR] of 0.56, 95% confidence interval [CI] 0.34-0.91). Complete vaccination was protective of admission with an aHR of 0.45 (95%CI 0.26-0.77).

Conclusion

Omicron has resulted in a lower risk of hospital admission, compared to contemporaneous Delta infection in the Western Cape Province, when using the proxy marker of RTD. Under-ascertainment of reinfections with an immune escape variant like Omicron remains a challenge to accurately assessing variant virulence.
Addressing selection bias in the UK Biobank neurological imaging cohort
Authors: Bradley Valerie , Nichols Thomas E.
Published: January 2022

The UK Biobank is a national prospective study of half a million participants between the ages of 40 and 69 at the time of recruitment between 2006 and 2010, established to facilitate research on diseases of aging. The imaging cohort is a subset of UK Biobank participants who have agreed to undergo extensive additional imaging assessments. However, Fry et al. (2017) finds evidence of “healthy volunteer bias” in the UK Biobank – participants are less likely to smoke, be obese, consume alcohol daily than the target population of UK adults. Here we examine selection bias in the UK Biobank imaging cohort. We address two common misconceptions: first, that study size can compensate for bias in data collection, and second that selection bias does not affect estimates of associations, which are the primary interest of the UK Biobank. We introduce inverse probability weighting (IPW) as an approach commonly used in survey research that can be used to address selection bias in volunteer health studies like the UK Biobank. We discuss 6 such methods – five existing and one novel –, assess relative performance in simulation studies, and apply them to the UK Biobank imaging cohort. We find that our novel method, BART for predicting the probability of selection combined with raking, performs well relative to existing methods, and helps alleviate selection bias in the UK Biobank imaging cohort.
Prom1 and Notch regulate ciliary length and dynamics in multiciliated cells of the airway epithelium
Authors: Serra Carlos F. H. , Liu Helu , Qian Jun , Mori Munemasa , Lu Jining , Cardoso Wellington V.
Published: January 2022

Differences in ciliary morphology and dynamics among multiciliated cells of the respiratory tract have been well reported and known to contribute to efficient mucociliary clearance. Nevertheless, little is known about how phenotypic differences among multiciliated cells are established in the mammalian lung. Here we show that Prominin-1 (Prom1), a transmembrane protein widely used as stem cell and tumor-initiating marker, is crucial to this process. During airway differentiation, Prom1 becomes restricted to multiciliated cells, where it is expressed at distinct levels along the proximal-distal axis of the airways and in the adult airway epithelium in vitro. We found that Prom1 is induced by Notch in post-specified multiciliated cells and that Notch inactivation abolishes the gradients of Prom1 in the developing airways and in differentiating organotypic cultures. Prom1 was not required for multicilia formation and when inactivated resulted in longer cilia, which remained functional but beating at a lower frequency. Disruption of Notch resulted in opposite effects and suggested that Notch fine-tunes Prom1 levels to regulate the multiciliated cell phenotype and generate diversity among these cells in the respiratory tract. By controlling these features, this mechanism contributes to the innate defense of the lung against environmental agents and prevent pulmonary disease.

Significance Statement

Multiciliated cells are integral components of the epithelia from a variety of organs. In the respiratory tract they are crucial for mucociliary clearance, a first line of defense against environmental agents and microorganisms. Regional differences in ciliary morphology and dynamics of multiciliated cells have been well described. However, little is known about the events generating phenotypical and functional differences among these cells in airways. Here we provide evidence of a novel mechanism in post-specified multiciliated progenitors whereby local Notch and Prom1 regulate ciliary length and ciliary beating to generate morphological and functional diversity among the multiciliated cells. The findings provide insights into the impact of these signals in maintaining the integrity and function of the airway epithelium, preventing pulmonary disease.
Time-lapsed proteomics reveals a role for the novel protein, SNED1, in modulating ECM composition and protein folding
Authors: Lee Fred , Shao Xinhao , Gao Yu (Tom) , Naba Alexandra
Published: January 2022

The extracellular matrix (ECM) is a complex and dynamic meshwork of proteins providing structural support to cells. It also provides biochemical signals governing cellular processes including proliferation and migration. Alterations of ECM structure and/or composition has been shown to lead to, or accompany, many pathological processes including cancer and fibrosis. To understand how the ECM contributes to diseases, we first need to obtain a comprehensive characterization of the ECM of tissues and of its changes during disease progression. Over the past decade, mass-spectrometry-based proteomics has become the state-of-the-art method to profile the protein composition of ECMs. However, existing methods do not fully capture the broad dynamic range of protein abundance in the ECM, nor do they permit to achieve the high coverage needed to gain finer biochemical information, including the presence of isoforms or post-translational modifications. In addition, broadly adopted proteomic methods relying on extended trypsin digestion do not provide structural information on ECM proteins, yet, gaining insights into ECM protein structure is critical to better understanding protein functions. Here, we present the optimization of a time-lapsed proteomic method using limited proteolysis of partially denatured samples and the sequential release of peptides to achieve superior sequence coverage as compared to standard ECM proteomic workflow. Exploiting the spatio-temporal resolution of this method, we further demonstrate how 3-dimensional time-lapsed peptide mapping can identify protein regions differentially susceptible to trypsin and can thus identify sites of post-translational modifications, including protein-protein interactions. We further illustrate how this approach can be leveraged to gain insight on the role of the novel ECM protein SNED1 in ECM homeostasis. We found that the expression of SNED1 by mouse embryonic fibroblasts results in the alteration of overall ECM composition and the sequence coverage of certain ECM proteins, raising the possibility that SNED1 could modify accessibility to trypsin by engaging in protein-protein interactions.
LiCl-induced sickness modulates spontaneous activity and response dynamics in rat gustatory cortex
Authors: Stone Bradly T. , Lin Jian-You , Mahmood Abuzar , Sanford Alden J. , Katz Donald B.
Published: January 2022

Gustatory Cortex (GC), a structure deeply involved in the making of consumption decisions, presumably performs this function by integrating information about taste, experiences, and internal states related to the animal’s health, such as illness. Here, we investigated this assertion, examining whether illness is represented in GC activity, and how this representation impacts taste responses and behavior. We recorded GC single-neuron activity and local field potentials (LFP) from healthy rats and (the same) rats made ill (via LiCl injection). We show (consistent with the extant literature) that the onset of illness-related behaviors arises contemporaneously with alterations in spontaneous 7-12Hz LFP power at ∼11 min following injection. This process was accompanied by reductions in single-neuron taste response magnitudes and discriminability, and with enhancements in palatability-relatedness – a result reflecting the collapse of responses toward a simple “good-bad” code arising in a specific subset of GC neurons. Overall, our data show that a state (illness) that profoundly reduces consumption changes basic properties of the sensory cortical response to tastes, in a manner that can easily explain illness’ impact on consumption.

Significance Statement

Neural responses in primary sensory cortex are often thought to faithfully represent physical stimuli, and while recent studies (including ours) have challenged this view by documenting enhancements and decrements in stimulus-induced firing related to animals’ internal states, there has been little work setting these changes in any sort of functional, mechanistic context. Here we show that a state (illness) that profoundly reduces consumption changes basic properties of the sensory cortical response to tastes, and then go beyond this to precisely characterize this response plasticity, connecting it to the specific perceptual changes that drive illness’ impact on consumption.
Origin of congenital coronary arterio-ventricular fistulae from anomalous epicardial and myocardial development
Authors: Palmquist-Gomes P , Ruiz-Villalba A , Guadix JA , Romero JP , Bessiéres B , MacGrogan D , Conejo L , Ortiz A , Picazo B , Houyel L , Gómez-Cabrero D , Meilhac SM , de la Pompa JL , Pérez-Pomares JM
Published: January 2022

Aims

In this work we investigated the embryonic origin of coronary arterio-ventricular connections, known as coronary artery fistulas (CAF), a congenital heart disease associated to postnatal and adult changes in systemic hemodynamics that may cause cardiac ischemia.

Methods and results

we have used different animal models (mouse and avian embryos) to experimentally model CAF morphogenesis. Conditional Itga4 (alpha 4 integrin) epicardial deletion in mice and cryocauterisation of chick and quail embryonic hearts disrupted epicardial development and ventricular wall growth, two essential events in coronary embryogenesis. Additional transcriptomics and in vitro analyses were performed to better understand how arterio-ventricular connections are originated in the embryonic heart. Our results show myocardial discontinuities in the developing heart of mutant mice presenting epicardial defects and avian embryos submitted to a physical cryodamage of the ventricle. These ventricular discontinuities promote the formation of endocardial pouch-like structures resembling human CAF. The structure of these CAF-like anomalies was compared with histopathological data from a human CAF, showing histomorphological and immunochemical similarities. Both human and mutant mouse hearts showed similar anomalies in the compaction of the ventricular myocardium. In vitro experiments showed the abnormal contact between the epicardium and the endocardium promote the precocious differentiation of epicardial cells to smooth muscle.

Conclusion

Our work suggests that myocardial discontinuities in the embryonic ventricular wall are a causative of CAF. These discontinuities would promote the early contact of the endocardium with epicardial-derived coronary progenitors at the cardiac surface, leading to ventricular endocardial extrusion, precocious differentiation of coronary smooth muscle cells, and the formation of pouch-like aberrant coronary-like structures in direct connection with the ventricular lumen.

Translational perspective

Congenital coronary artery fistulas (CAFs) lead to complications such as myocardial hypertrophy, endocarditis, heart dilatation and failure. Unfortunately, and despite their clinical relevance, the origins these congenital anomalies remain unknown. In this work, we provide information on the developmental mechanisms involved in the formation of CAFs that is relevant for their early diagnosis and prevention.
In vitro Kinase-to-Phosphosite database (iKiP-DB) predicts kinase activity in phosphoproteomic datasets
Authors: Mari Tommaso , Mösbauer Kirstin , Wyler Emanuel , Landthaler Markus , Drosten Christian , Selbach Matthias
Published: January 2022

Phosphoproteomics routinely quantifies changes in the levels of thousands of phosphorylation sites, but functional analysis of such data remains a major challenge. While databases like PhosphoSitePlus contain information about many phosphorylation sites, the vast majority of known sites are not assigned to any protein kinase. Assigning changes in the phosphoproteome to the activity of individual kinases therefore remains a key challenge.. A recent large-scale study systematically identified in vitro substrates for most human protein kinases. Here, we reprocessed and filtered these data to generate an in vitro Kinase-to-Phosphosite database (iKiP-DB). We show that iKiP-DB can accurately predict changes in kinase activity in published phosphoproteomic datasets for both well-studied and poorly characterized kinases. We apply iKiP-DB to a newly generated phosphoproteomic analysis of SARS-CoV-2 infected human lung epithelial cells and provide evidence for coronavirus-induced changes in host cell kinase activity. In summary, we show that iKiP-DB is widely applicable to facilitate the functional analysis of phosphoproteomic datasets.
An essential function for autocrine Hedgehog signaling in epithelial proliferation and differentiation in the trachea
Authors: Yin Wenguang , Liontos Andreas , Koepke Janine , Ghoul Maroua , Mazzocchi Luciana , Liu Xinyuan , Lu Chunyan , Wu Haoyu , Fysikopoulos Athanasios , Sountoulidis Alexandros , Seeger Werner , Ruppert Clemens , Günther Andreas , Stainier Didier Y.R. , Samakovlis Christos
Published: January 2022

The tracheal epithelium is a primary target for pulmonary diseases as it provides a conduit for air flow between the environment and the lung lobes. The cellular and molecular mechanisms underlying airway epithelial cell proliferation and differentiation remain poorly understood. Hedgehog (Hh) signaling orchestrates communication between epithelial and mesenchymal cells in the lung, where it modulates stromal cell proliferation, differentiation and signaling back to the epithelium. Here, we reveal a new, autocrine function of Hh signaling in airway epithelial cells. Epithelial cell depletion of the ligand Sonic hedgehog (SHH) or its effector Smoothened (SMO) causes defects in both epithelial cell proliferation and differentiation. In cultured primary human airway epithelial cells, Hh signaling inhibition also hampers cell proliferation and differentiation. Epithelial Hh function is mediated, at least in part, through transcriptional activation as Hh signaling inhibition leads to downregulation of cell-type specific transcription factor genes in both the mouse trachea and human airway epithelial cells. These results provide new insights into the role of Hh signaling in epithelial cell proliferation and differentiation during airway development.
Nicotinic signaling is required for motor learning but not rehabilitation after spinal cord injury
Authors: Li Yue , Hollis Edmund R
Published: January 2022

Currently, therapeutic intervention for spinal cord injury is limited. Many approaches rely on strengthening the remaining substrate and driving recovery through rehabilitative training. As compared to learning novel compensatory strategies, rehabilitation focuses on restoring movements lost to injury. Whether rehabilitation of previously learned movements after spinal cord injury requires the molecular mechanisms of motor learning, or if it engages previously trained motor circuits without requiring novel learning. Our findings implicate the latter mechanism, as we demonstrate that nicotinic acetylcholine signaling is required for motor learning but is dispensable for the recovery of previously trained motor behavior after cervical spinal cord injury.
Environmental factors shape the culturable bacterial diversity in deep-sea water and surface sediments from the Mariana Trench
Authors: Ma Yuewei , Ding Wenmian , Wang Yuepeng , Chen Ping , Zhou Hui , Li Xuan , Huang Yanyan , Nan Peng
Published: January 2022

Hailed as “The Fourth Pole”, the Mariana Trench is the deepest part of the ocean. The microbial diversity in it is extremely complicated, which might be caused by the unique environmental factors such as high salinity, low temperature, high hydrostatic pressure, and limited nutrition. Based on 4 seawater samples and 4 sediment samples obtained from the Mariana Trench, we isolated and fostered the microorganism clones with kinds of culture mediums and high-throughput culturing. By using the molecular identification methods based on PCR of 16S rDNA and ITS gene, 1266 bacterial strains in total were isolated and identified, which affiliated to 7 classes, 16 orders, 25 families and 36 genera in four phyla : Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes. Strains in genera Halomonas, Pseudoaltermonas were the dominant bacteria isolated from the samples. With Mantel tests on the sample-environmental parameter matrix, the sample-environmental organic matter diversity matrix and the sample-microbial diversity matrix, we concluded that the environmental parameters and the organic matters in the condition can shape the culturable bacterial diversity in deep-sea water and surface sediments from the Mariana Trench.
Contextual associations represented both in neural networks and human behavior
Authors: Aminoff Elissa M. , Baror Shira , Roginek Eric W. , Leeds Daniel D.
Published: January 2022

Contextual associations facilitate object recognition in human vision. However, the role of context in artificial vision remains elusive as does the characteristics that humans use to define context. We investigated whether contextually related objects (bicycle-helmet) are represented more similarly in convolutional neural networks (CNNs) used for image understanding than unrelated objects (bicycle-fork). Stimuli were of objects against a white background and consisted of a diverse set of contexts (N=73). CNN representations of contextually related objects were more similar to one another than to unrelated objects across all CNN layers. Critically, the similarity found in CNNs correlated with human behavior across three experiments assessing contextual relatedness, emerging significant only in the later layers. The results demonstrate that context is inherently represented in CNNs as a result of object recognition training, and that the representation in the later layers of the network tap into the contextual regularities that predict human behavior.
The immune synapses reveal aberrant functions of CD8 T cells during chronic HIV infection
Authors: Anikeeva Nadia , Steblyanko Maria , Kuri-Cervantes Leticia , Buggert Marcus , Betts Michael R. , Sykulev Yuri
Published: January 2022

It is well-established that chronic HIV infection causes persistent low-grade inflammation that induces premature aging of the immune system in HIV patient including senescence of memory and effector CD8 T cells. To uncover the reasons of gradually diminished potency of CD8 T cells from chronically HIV infected people, we have analyzed cellular morphology and dynamics of the synaptic interface followed exposure of peripheral polyclonal CD8 T cells at various differentiation stages to planar lipid bilayers. The above parameters were linked to pattern of degranulation that determines efficiency of CD8 T cells cytolytic response. We found a large fraction of naive T cells from HIV infected people developing mature synapses and demonstrating focused degranulation, a signature of a differentiated T cells. Further differentiation of aberrant naïve T cells leads to development of anomalous effector T cells undermining their capacity to control HIV and other viruses that could be contained otherwise.
The effect of mainland dynamics on data and parameter estimates in island biogeography
Authors: Lambert Joshua W. , Santos Neves Pedro , Bilderbeek Richèl J.C. , Valente Luis , Etienne Rampal S.
Published: January 2022

Understanding macroevolution on islands requires knowledge of the closest relatives of is-land species on the mainland. The evolutionary relationships between island and mainland species can be reconstructed using phylogenies, to which models can be fitted to understand the dynamical processes of colonisation and diversification. But how much information on the mainland is needed to gain insight into macroevolution on islands? Here we first test whether species turnover on the mainland and incomplete mainland sampling leave recognis-able signatures in community phylogenetic data. We find predictable phylogenetic patterns: colonisation times become older and the perceived proportion of endemic species increases as mainland turnover and incomplete knowledge increase. We then analyse the influence of these factors on the inference performance of the island biogeography model DAISIE, a whole-island community phylogenetic model that assumes that mainland species do not diversify, and that the mainland is fully sampled in the phylogeny. We find that colonisation and diversification rate are estimated with little bias in the presence of mainland extinction and incomplete sampling. By contrast, the rate of anagenesis is overestimated under high levels of mainland extinction and incomplete sampling, because these increase the perceived level of island endemism. We conclude that community-wide phylogenetic and endemism datasets of island species carry a signature of mainland extinction and sampling. The ro-bustness of parameter estimates suggests that island diversification and colonisation can be studied even with limited knowledge of mainland dynamics.
The assembled Banana dihaploid mitochondrial genome is compact with a high number of gene copies
Authors: Prakash Shruthy Priya , Chandrasekar Vaidheki , Subramanian Selvi , Ummar Rahamatthunnisha
Published: January 2022

Banana being a major food crop all around the world, attracts various research interests in crop improvement. In banana, complete genome sequences of Musa accuminata and Musa balbisiana are available. However, the mitochondrial genome is not sequenced or assembled. Mitochondrial (mt) genes play an important role in flower and seed development and in Cytoplasmic Male Sterility. Unraveling banana mt genome architecture will be a foundation for understanding inheritance of traits and their evolution. In this study, the complete banana mt genome is assembled from the whole genome sequence data of the Musa acuminata subsp. malaccensis DH-Pahang. The mt genome sequence acquired by this approach was 409574 bp and it contains, 54 genes coding for 25 respiratory complex proteins 15 ribosomal proteins, 12 tRNA genes and two ribosomal RNA gene. Except atpB, rps11 and rps19 other genes are in multiple copies. The copy number is 12 in tRNA genes. In addition, nearly 25% tandem repeats are also present in it. These mt proteins are identical to the mt proteins present in the other members of AA genome and share 98% sequence similarity with M. balbisiana. The C to U RNA editing is profoundly higher (87 vs 13%) in transcripts of M. balbisiana (BB) compared to M. accuminata (AA). The banana AA mitochondrial genome is tightly packed with 233 genes, with less rearrangements and just 5.3% chloroplast DNA in it. The maintenance of high copy number of functional mt genes suggest that they have a crucial role in the evolution of banana.
Rab35 Governs Apicobasal Polarity Through Regulation of Actin Dynamics During Sprouting Angiogenesis
Authors: Francis Caitlin R. , Kincross Hayle , Kushner Erich J.
Published: January 2022

In early blood vessel development, trafficking programs, such as those using Rab GTPases, are tasked with delivering vesicular cargo with high spatiotemporal accuracy. However, the function of many Rab trafficking proteins remain ill-defined in endothelial tissue; therefore, their relevance to blood vessel development is unknown. Rab35 has been shown to play an enigmatic role in cellular behaviors which differs greatly between tissue-type and organism. Importantly, Rab35 has never been characterized for its potential contribution in sprouting angiogenesis; thus, our goal was to map Rab35’s primary function in angiogenesis. Our results demonstrate that Rab35 is critical for sprout formation; in its absence apicobasal polarity is entirely lost in vitro and in vivo. To determine mechanism, we systematically explored established Rab35 effectors and show that none are operative in endothelial cells. However, we find that Rab35 partners with DENNd1c, an evolutionarily divergent guanine exchange factor, to localize to actin. Here, Rab35 regulates actin polymerization, which is required to setup proper apicobasal polarity during sprout formation. Our findings establish that Rab35 is a potent regulator of actin architecture during blood vessel development.
RefZ and Noc act synthetically to prevent aberrant divisions during Bacillus subtilis sporulation
Authors: Miller Allyssa K. , Herman Jennifer K.
Published: January 2022

During sporulation, Bacillus subtilis undergoes an atypical cell division that requires overriding mechanisms which protect chromosomes from damage and ensure inheritance by daughter cells. Instead of assembling between segregated chromosomes at midcell, the FtsZ-ring (Z-ring) coalesces polarly, directing division over one chromosome. The DNA-binding protein RefZ facilitates the timely assembly of polar Z-rings and partially defines the region of chromosome initially captured in the forespore. RefZ binds to motifs (RBMs) located proximal to the origin of replication (oriC). Although refZ and the RBMs are conserved across the Bacillus genus, a refZ deletion mutant sporulates with wildtype efficiency, so the functional significance of RefZ during sporulation remains unclear. To further investigate RefZ function, we performed a candidate-based screen for synthetic sporulation defects by combining ΔrefZ with deletions of genes previously implicated in FtsZ regulation and/or chromosome capture. Combining ΔrefZ with deletions of ezrA, sepF, parA, or minD did not detectably affect sporulation. In contrast, a ΔrefZ Δnoc mutant exhibited a sporulation defect, revealing a genetic interaction between RefZ and Noc. Using reporters of sporulation progression, we determined the ΔrefZ Δnoc mutant exhibited sporulation delays after Spo0A activation but prior to late sporulation, with a subset of cells failing to divide polarly or activate the first forespore-specific sigma factor, SigF. The ΔrefZ Δnoc mutant also exhibited extensive dysregulation of cell division, producing cells with extra, misplaced, or otherwise aberrant septa. Our results reveal a previously unknown epistatic relationship that suggests refZ and noc contribute synthetically to regulating cell division and supporting spore development.

IMPORTANCE

The DNA-binding protein RefZ and its binding sites (RBMs) are conserved in sequence and location on the chromosome across the Bacillus genus and contribute to the timing of polar FtsZ-ring assembly during sporulation. Only a small number of non-coding and non-regulatory DNA motifs are known to be conserved in chromosomal position in bacteria, suggesting there is strong selective pressure for their maintenance; however a refZ deletion mutant sporulates efficiently, providing no clues as to their functional significance. Here we find that in the absence of the nucleoid occlusion factor Noc, deletion of refZ results in a sporulation defect characterized by developmental delays and aberrant divisions.
Bat Red Blood Cells express Nucleic Acid Sensing Receptors and bind RNA and DNA
Authors: Lam LK Metthew , Dobkin Jane , Eckart Kaitlyn A. , Gereg Ian , DiSalvo Andrew , Nolder Amber , Anis Eman , Ellis Julie C. , Turner Greg , Mangalmurti Nilam S.
Published: January 2022

Red blood cells (RBCs) demonstrate immunomodulatory capabilities through the expression of nucleic acid sensors. However, little is known about bat RBCs, and no studies have examined the immune function of bat erythrocytes. Here we show that bat RBCs express the nucleic acid-sensing Toll-like receptors TLR7 and TLR9 and bind the nucleic acid ligands, single-stranded RNA, and CpG DNA. Collectively, these data suggest that, like human RBCs, bat erythrocytes possess immune function and may be reservoirs for nucleic acids. These findings provide unique insight into bat immunity and may uncover potential mechanisms by which virulent pathogens in humans are concealed in bats.
OrganoID: a versatile deep learning platform for tracking and analysis of single-organoid dynamics
Authors: Matthews Jonathan , Schuster Brooke , Kashaf Sara Saheb , Liu Ping , Ben-Yishay Rakefet , Ishay-Ronen Dana , Shen Le , Weber Christopher , Bielski Margaret , Kupfer Sonia S. , Bilgic Mustafa , Rzhetsky Andrey , Tay Savaş
Published: January 2022

Organoids have immense potential as ex vivo disease models for drug discovery and personalized drug screening. Dynamic changes in individual organoid morphology, number, and size can indicate important drug responses, however these metrics are difficult and labor-intensive to obtain for high-throughput image datasets. Here, we present OrganoID, a robust image analysis platform that automatically recognizes, labels, and tracks single organoids, pixel-by-pixel, in brightfield and phase-contrast microscopy experiments. The platform was trained on images of pancreatic cancer organoids and validated on separate images of pancreatic, lung, colon, and adenoid cystic carcinoma organoids, which showed excellent agreement with manual measurements of organoid count (96%) and size (95%) without any parameter adjustments. Single-organoid tracking accuracy remained above 89% over a four-day time-lapse microscopy study. Automated single-organoid morphology analysis of a chemotherapy dose-response experiment identified decreased organoid circularity as an important morphological feature reflecting drug response. OrganoID enables straightforward, detailed, and accurate image analysis to accelerate the use of organoids in high-throughput, data-intensive biomedical applications.
Multifunctional properties of Nej1XLF C-terminus promote end-joining and impact DNA double-strand break repair pathway choice
Authors: Mojumdar Aditya , Adam Nancy , Cobb Jennifer
Published: January 2022

A DNA double strand break (DSB) is primarily repaired by one of two canonical pathways, non-homologous end-joining (NHEJ) and homologous recombination (HR). NHEJ requires no or minimal end processing for ligation, whereas HR requires 5’ end resection followed by a search for homology. The main event that determines the mode of repair is the initiation of 5’ resection because if resection starts, then NHEJ cannot occur. Nej1 is a canonical NHEJ factor that functions at the cross-roads of repair pathway choice and prior to its function in stimulating Dnl4 ligase. Nej1 competes with Dna2, inhibiting its recruitment to DSBs and thereby inhibiting resection. The highly conserved C-terminal region (CTR) of Nej1 (330-338) is important for two events that drive NHEJ, stimulating ligation and inhibiting resection, but it is dispensable for end-bridging. By combining nej1 point mutants with nuclease-dead dna2-1, we find that Nej1-F335 is essential for end-joining whereas V338 promotes NHEJ indirectly through inhibiting Dna2-mediated resection.

Highlights

Nej1 C-terminus is critical for repair pathway choice.

The KKRK region of Nej1 is important for interactions with ssDNA and dsDNA.

Nej1-F335 and V338 are key residues for end-joining and inhibition of resection at DSB.

Nej1-mediated end-bridging is not sufficient for end-joining repair.
A biphasic Deep Semi-supervised framework for Suptype Classification and biomarker discovery
Authors: Le Hoang , Nguyen Van-Minh , Nguyen Quang-Huy , Le Duc-Hau
Published: January 2022

To take full advantage of the unprecedented development of -omics technologies and generate further biological insights into human disease, it is a pressing need to develop novel computational methods for integrative analysis of multi-omics data. Here we proposed a biphasic Deep Semi-supervised multi-omics integration framework for Subtype Classification and biomarker discovery, DeepSSC. In phase 1, each denoising autoencoder was used to extract a compact representation for each -omics data, and then they were concatenated and put into a feed-forward neural network for subtype classification. In phase 2, our Biomarker Gene Identification procedure leveraged that neural network classifier to render subtype-specific important biomarkers. We also validated our given results on independent dataset. We demonstrated that DeepSSC exhibited better performance over other state-of-the-art techniques concerning classification tasks. As a result, DeepSSC successfully detected well-known biomarkers and hinted at novel candidates from different -omics data types related to the investigated biomedical problems.
The bladder microbiome, metabolome, cytokines, and phenotypes in patients with systemic lupus erythematosus
Authors: Liu Fengping , Du Jingjie , Zhai Qixiao , Hu Jialin , Miller Aaron W. , Ren Tianli , Feng Yangkun , Jiang Peng , Hu Lei , Sheng Jiayi , Gu Chaoqun , Yan Ren , Lv Longxian , Wolfe Alan J. , Feng Ninghan
Published: January 2022

Background and aims

Emerging studies reveal a unique bacterial community in the human bladder, with alteration of composition associated to disease states. Systemic lupus erythematosus (SLE) is a complex autoimmune disease that is characterized by frequent impairment of the kidney. Here, we explored the bladder microbiome, metabolome, and cytokine profiles in SLE patients, as well as correlations between microbiome and metabolome, cytokines, and disease profiles.

Methods and materials

We recruited a cohort of 50 SLE patients and 50 individually matched asymptomatic controls. We used transurethral catheterization to collect urine samples, 16S rRNA gene sequencing to profile bladder microbiomes, and LC-MS/MS to perform untargeted metabolomic profiling.

Results

Compared to controls, SLE patients possessed a unique bladder microbial community and increased alpha diversity. These differences were accompanied by differences in urinary metabolomes, cytokines, and patients’ disease profiles. The SLE-enriched genera, including Bacteroides, were positively correlated with several SLE-enriched metabolites, including olopatadine. The SLE-depleted genera, such as Pseudomonas, were negatively correlated to SLE-depleted cytokines, including IL-8. Alteration of the bladder microbiome was associated with disease profile. For example, the genera Megamonas and Phocaeicola were negatively correlated with serum complement C3, and Streptococcus was positively correlated with IgG.

Conclusions

Our present study reveals associations between the bladder microbiome and the urinary metabolome, cytokines, and disease phenotypes. Our results could help identify biomarkers for SLE.
Efficacy, Practicality, Intimal Health, and Sustainability of Menstrual Cups use among Undergraduate Medical Students: a cross-sectional study
Authors: Lobascz Brenda Czekalski , de França Reis Maria Beatriz , e Tiburcio Mendes Gabriella de Perez Monteiro , de Oliveira Cruz Danillo Christian , Ferreira Damaceno Maria Jose Caetano , Sartorao Filho Carlos Izaias
Published: January 2022

Introduction

Women need effective, safe, and affordable menstrual hygiene products. The menstrual cup is an alternative method.

Objective

To identify the prevalence of menstrual cups among the medical students and the independent variables associated with their use adherence.

Methods

a cross-sectional study with an online survey applied to regularly matriculate women from FEMA Medical School in January 2021.

Results

Of 277 women, 164 participated. The mean age was 22.26 (SD 3.21). 136 preferred external pads, 60 internal pads, 28 menstrual cups, and 11 did not use. Using a 1-10 scale, price, efficacy, sustain, practice, intimal health status, hygiene, and importance of internal genitalia integrity were questioned. 37 (22,56%) women related the use of menstrual cups in the last year. Using any method to reduce menstruation had an odds ratio adjusted of 0.310 (95%CI 0.122-0.787). Concern about the environmental biodegradation had ORadj of 6.369 (95%CI 1.372-29.562); Intimal Health, ORadj of 1.996 (95%CI 1.183-3.368); internal genital integrity, ORadj of 0.824 (95%CI 0.682-0.995), for menstrual cups use.

Conclusion

women using a method to reduce their menstrual flow, concerning about biodegradation, concerning with intimal health, and with no concerns about manipulating their genitalia were significant independent factors for the adherence of menstrual cups.