bluuebunny/crossref_metadata_2025 huggingface dataset:
Family responsibilities and mental health of kindergarten educators during the first COVID-19 pandemic lockdown in Ontario, Canada
Authors: Spadafora Natalie , Reid-Westoby Caroline , Pottruff Molly , Janus Magdalena
Published: May 2021

The present study, conducted during the first wave of the COVID-19 pandemic in Ontario, Canada, addressed the association between family responsibilities and mental health (depression and anxiety) among kindergarten educators. Participants comprised 1,790 (97.9% female) kindergarten educators (73.6% kindergarten teachers; 26.4% early childhood educators) across Ontario. Results revealed that educators were more likely to report moderate levels of depressive symptoms if they had the responsibility of caring for their own children, and more likely to report moderate levels of depressive and anxious symptoms if they had the responsibility of caring for an older adult. Theoretical and practical implications are discussed.
Integrative Analyses Reveal Novel Disease-associated Loci and Genes for Idiopathic Pulmonary Fibrosis
Authors: Chen Ming , Zhang Yiliang , Adams Taylor S. , Ji Dingjue , Jiang Wei , Wain Louise V. , Cho Michael H. , Kaminski Naftali , Zhao Hongyu
Published: May 2021

Background

Although genome-wide association studies have identified many genomic regions associated with idiopathic pulmonary fibrosis (IPF), the causal genes and functions remain largely unknown. Many bulk and single-cell expression data have become available for IPF, and there is increasing evidence suggesting a shared genetic basis between IPF and other diseases.

Methods

By leveraging shared genetic information and transcriptome data, we conducted an integrative analysis to identify novel genes for IPF. We first considered observed phenotypes, polygenic risk scores, and genetic correlations to investigate associations between IPF and other traits in the UK Biobank. We then performed local genetic correlation analysis and cross-tissue transcriptome-wide association analysis (TWAS) to identify IPF genes. We further prioritized genes using bulk and single-cell gene expression data.

Findings

We identified 25 traits correlated with IPF on the phenotype level and seven traits genetically correlated with IPF. Using local genetic correlation, we identified 12 candidate genes across 14 genomic regions, including the POT1 locus (p-value = 4·1E-4), which contained variants with protective effects on lung cancer but increasing IPF risk. Using TWAS, we identified 36 genes, including 12 novel genes for IPF. Annotation-stratified heritability estimation and differential expression analysis of downstream-regulated genes suggested regulatory roles of two candidate genes, MAFK and SMAD2, on IPF.

Interpretation

Our integrative analysis identified new genes for IPF susceptibility and expanded the understanding of the complex genetic architecture of IPF.

Funding

NIHR Leicester Biomedical Research Centre, Three Lakes Partners, the National Institutes of Health, the National Science Foundation, U01HL145567, and UH2HL123886.
Perception and Attitudes of Medical Students Regarding Postoperative Pain Management
Authors: Johora Fatema , Abbasy Asma Akter , Jeenia Fatiha Tasmin , Sojib Ferdaush Ahmed , Aktar Mohsena , Moitra Priyanka , Ferdoush Jannatul , Momen Afroza , Ali Mohammad
Published: May 2021

Background

Postoperative pain remains a challenging problem, which requires a dynamic approach using a variety of treatment modalities to obtain an optimal outcome with respect to enhancing patient comfort and facilitating the recovery process. Multimodal analgesia signifies an increasingly popular approach to prevent postoperative pain. The approach includes administering a combination of opioid and nonopioid analgesics that act at different sites within the central and peripheral nervous systems in an effort to improve pain control while eliminating opioid-related adverse effects.

Materials and Methods

To understand the perception and attitude of 4th year medical students, a structured questionnaire survey was done among six different medical colleges including government (Armed Forces Medical College, Cumilla Medical College and Colonel Malek Medical College, Manikganj) and non-government medical colleges (Army Medical College Bogura, Brahmanbaria Medical College and Chattogram International Medical College) of Bangladesh in October 2019. Total 340 students participated in the study.

Result

Among the 340 students, almost 336 (98.2%) students were agreed that postoperative pain management is an essential element of patient care. Only 4 (1.18%) respondents disagreed. On the other hand, regarding its influence on early recovery and reduction of hospital staying, 311 (91.47%) respondents agreed and 29 (8.53%) respondents were found as disagreed. Regarding the issue of opioid commonly induced respiratory depression, 257 (75.59%) respondents thought it is a common adverse event and 81 (23.82%) respondents disagreed. 206 (60.59%) respondents didn’t agree that opioid always produce addiction or tolerance and 134 (39.71%) respondents disagreed with the same issue. 294 (86) respondents agreed that multimodal analgesia increases patient’s cost and 46 (14%) disagreed. 249 (74%) students agreed that regional techniques are useful for postoperative pain management and 89 (26%) respondents disagreed.

Conclusion

Adequate post-operative pain management knowledge is necessary to reduce post-operative complications.
Temporal Dynamics of Neural Processing of Facial Expressions and Emotions
Authors: Nara Sanjeev , Rathee Dheeraj , Molinaro Nicola , Bois Naomi Du , Bhushan Braj , Prasad Girijesh
Published: May 2021

Emotion processing has been a focus of research in psychology and neuroscience for some decades. While the evoked neural markers in human brain activations in response to different emotions have been reported, the temporal dynamics of emotion processing has received less attention. Differences in processing speeds, that depend on emotion type, have not been determined. Furthermore, behavioral studies have found that the right side of the human face expresses emotions more accurately than the left side. Therefore, accounting for both the content of the emotion and the visual angle of presentation from the perspective of the viewer, here we have investigated variability in the discrimination of happy and sad faces when the visual angle of presentation was Positive (right side of the face) compared to Negative (left side of the face). Furthermore, the temporal dynamics involved in processing happy and sad emotions have been compared. Regardless of visual angle, happy emotions were processed faster than sad emotions. However, the evoked response to sad emotions significantly increased in amplitude compared to that for happy emotions, when faces were presented at Positive visual angles only. Source reconstruction from sensor-level ERFs show localized activities in ventral and dorsal stream, including fusiform gyrus, lingual gyrus, putamen and Pre and Post central gyrus. Multivariate pattern analysis (MVPA) confirmed these findings – demonstrating successful decoding of happy and sad emotions only occurred when the facial expression was viewed from a positive visual angle, and that happy emotions were processed faster than sad emotions.
Dynein light chain-dependent dimerization of Egalitarian is essential for maintaining oocyte fate in Drosophila
Authors: Neiswender Hannah , Goldman Chandler H. , Veeranan-Karmegam Rajalakshmi , Gonsalvez Graydon B.
Published: May 2021

Egalitarian (Egl) is an RNA adaptor for the Dynein motor and is thought to link numerous, perhaps hundreds, of mRNAs with Dynein. Dynein, in turn, is responsible for the transport and localization of these mRNAs. Studies have shown that efficient mRNA binding by Egl requires the protein to dimerize. We recently demonstrated that Dynein light chain (Dlc) is responsible for facilitating the dimerization of Egl. Mutations in Egl that fail to interact with Dlc do not dimerize, and as such, are defective for mRNA binding. Consequently, this mutant does not efficiently associate with BicaudalD (BicD), the factor responsible for linking the Egl/mRNA complex with Dynein. In this report, we tested whether artificially dimerizing this Dlc-binding mutant using a leucine zipper would restore mRNA binding and rescue mutant phenotypes in vivo. Interestingly, we found that although artificial dimerization of Egl restored BicD binding, it only partially restored mRNA binding. As a result, Egl-dependent phenotypes, such as oocyte specification and mRNA localization, were only partially rescued. We hypothesize that Dlc-mediated dimerization of Egl results in a three-dimensional conformation of the Egl dimer that is best suited for mRNA binding. Although the leucine zipper restores Egl dimerization, it likely does not enable Egl to assemble into the conformation required for maximal mRNA binding activity.
TAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations
Authors: Cheng Yubao , Liu Miao , Hu Mengwei , Wang Siyuan
Published: May 2021

Background

Topologically associating domains (TADs) are important building blocks of three-dimensional genome architectures. The formation of TADs was shown to depend on cohesin in a loop-extrusion mechanism. Recently, advances in an image-based spatial genomics technique known as chromatin tracing led to the discovery of cohesin-independent TAD-like structures, also known as single-cell domains — highly variant self-interacting chromatin domains with boundaries that occasionally overlap with TAD boundaries but tend to differ among single cells and among single chromosome copies. Recent computational modeling studies suggest that epigenetic interactions may underlie the formation of the single-cell domains.

Results

Here we use chromatin tracing to visualize in female human cells the fine-scale chromatin folding of inactive and active X chromosomes, which are known to have distinct global epigenetic landscapes and distinct population-averaged TAD profiles, with inactive X chromosomes largely devoid of TADs and cohesin. We show that both inactive and active X chromosomes possess highly variant single-cell domains across the same genomic region despite the fact that only active X chromosomes show clear TAD structures at the population level. These X chromosome single-cell domains exist in distinct cell lines. Perturbations of major epigenetic components did not significantly affect the frequency or strength of the single-cell domains. Increased chromatin compaction of inactive X chromosomes occurs at a length scale above that of the single-cell domains.

Conclusions

In sum, this study suggests that single-cell domains are genome architecture building blocks independent of the tested major epigenetic components.
Selective recruitment of endoplasmic reticulum-targeted and cytosolic mRNAs into membrane-associated stress granules
Authors: Child Jessica R. , Chen Qiang , Reid David W. , Jagannathan Sujatha , Nicchitta Christopher V.
Published: May 2021

Stress granules (SGs) are membraneless organelles composed of mRNAs and RNA binding proteins which undergo assembly in response to stress-induced inactivation of translation initiation. The biochemical criteria for mRNA recruitment into SGs are largely unknown. In general, SG recruitment is limited to a subpopulation of a given mRNA species and RNA-seq analyses of purified SGs revealed that signal sequence-encoding (i.e. endoplasmic reticulum (ER)-targeted) transcripts are significantly under-represented, consistent with prior reports that ER-localized mRNAs are excluded from SGs. Using translational profiling, cell fractionation, and single molecule mRNA imaging, we examined SG biogenesis during the unfolded protein response (UPR) and report that UPR-elicited SG formation is gene selective. Combined immunofluorescence-smFISH studies demonstrated that UPR-induced mRNA granules co-localized with SG protein markers and were in close physical proximity to or directly associated with the ER membrane. mRNA recruitment into ER-associated SGs required stress-induced translational inhibition, though translational inhibition was not solely predictive of mRNA accumulation in SGs. SG formation in response to UPR activation or arsenite addition was blocked by the transcriptional inhibitors actinomycin D or triptolide, suggesting a functional link between gene transcriptional state and SG biogenesis. These data demonstrate that ER-targeted mRNAs can be recruited into SGs and identify the ER as a subcellular site of SG assembly. On the basis of the transcriptional inhibitor studies, we propose that newly transcribed mRNAs undergoing nuclear export during conditions of suppressed translation initiation are key substrates for SG biogenesis.
Distinct developmental mechanisms influence sexual dimorphisms in the milkweed bugOncopeltus fasciatus
Authors: Just Josefine , Laslo Mara , Lee Ye Jin , Yarnell Michael , Zhang Zhuofan , Angelini David R.
Published: May 2021

Sexual dimorphism is common in animals. The most complete model of sex determination comes fromDrosophila melanogaster, where the relative dosage of autosomes and X chromosomes leads indirectly to sex-specific transcripts ofdoublesex. Female Dsx interacts with a mediator complex protein encoded byintersexto activate female development. In males the transcription factor encoded byfruitlesspromotes male-specific behavior. The genetics of sex determination have been examined in a small number of other insects, yet several questions remain about the pleisomorphic state. Isdoublesexrequired for female and male development? Isfruitlessconserved in male behavior or morphology? Are other components such asintersexfunctionally conserved? To address these questions, we report expression and functional tests ofdoublesex, intersexandfruitlessin the hemipteranOncopeltus fasciatus, characterizing three sexual dimorphisms.doublesexprevents intersex phenotypes in all sexes and dimorphic traits in the milkweed bug.intersexandfruitlessare expressed across the body, in females and males.fruitlessandintersexalso affect the genitalia of both sexes, but have effects limited to different dimorphic structures in different sexes. These results reveal roles forintersexandfruitlessdistinct from other insects, and demonstrate distinct development mechanisms in different sexually dimorphic structures.
Dynamical Origin for Winner-Take-All Competition in A Biological Network of The Hippocampal Dentate Gyrus
Authors: Kim Sang-Yoon , Lim Woochang
Published: May 2021

We consider a biological network of the hippocampal dentate gyrus (DG). The DG is a pre-processor for pattern separation which facilitates pattern storage and retrieval in the CA3 area of the hippocampus. The main encoding cells in the DG are the granule cells (GCs) which receive the input from the entorhinal cortex (EC) and send their output to the CA3. We note that the activation degree of GCs is so low (~ 5%). This sparsity has been thought to enhance the pattern separation. We investigate the dynamical origin for winner-take-all (WTA) competition which leads to sparse activation of the GCs. The whole GCs are grouped into lamellar clusters. In each GC cluster, there is one inhibitory (I) basket cell (BC) along with excitatory (E) GCs. There are three kinds of external inputs into the GCs; the direct excitatory EC input, the indirect inhibitory EC input, mediated by the HIPP (hilar perforant path-associated) cells, and the excitatory input from the hilar mossy cells (MCs). The firing activities of the GCs are determined via competition between the external E and I inputs. The E-I conductance ratio (given by the time average of the external E to I conductances) may represents well the degree of such external E-I input competition. It is thus found that GCs become active when their is larger than a threshold , and then the mean firing rates of the active GCs are strongly correlated with . In each GC cluster, the feedback inhibition of the BC may select the winner GCs. GCs with larger than the threshold survive, and they become winners; all the other GCs with smaller become silent. In this way, WTA competition occurs via competition between the firing activity of the GCs and the feedback inhibition from the BC in each GC cluster. In this case, the hilar MCs are also found to play an essential role of enhancing the WTA competition in each GC cluster by exciting both the GCs and the BC.

PACS numbers: 87.19.lj, 87.19.lm, 87.19.lv
A chemically-defined growth medium to support Lactobacillus – Acetobacter community analysis
Authors: Aumiller Kevin , Stevens Eric , Scheffler Robert , Tüzün Güvener Zehra , Tung Emily , Grimaldo Anna B. , Carlson Hans K. , Deutschbauer Adam M. , Taga Michiko E. , Marco Maria L. , Ludington William B.
Published: May 2021

Lactobacilli and acetobacters are commercially important bacteria that often form communities in natural fermentations, including food preparations, spoilage, and in the digestive tract of Drosophila melanogaster fruit flies. Communities of these bacteria are widespread and prolific, despite numerous strain-specific auxotrophies, suggesting they have evolved nutrient interdependencies that regulate their growths. The use of a chemically-defined medium (CDM) supporting the growth of both groups of bacteria would greatly facilitate identification of the precise metabolic interactions between these two groups of bacteria. While numerous such media have been developed that support specific strains of lactobacilli and acetobacters, there has not been a medium formulated to support both genera. We developed such a medium, based on a previous Lactobacillus CDM, by modifying the nutrient abundances to improve growth of both groups of bacteria. We further simplified the medium by substituting casamino acids for individual amino acids and the standard Wolfe’s vitamins and mineral stocks for individual vitamins and minerals, resulting in a reduction from 40 to 8 stock solutions. The new CDM and variations of it support robust growth of lactobacilli and acetobacters. We provide the composition and an example of its use to measure nutritional interactions.
A Method for Rapid Flow-cytometric Isolation of Endothelial Nuclei and RNA from Archived Frozen Brain Tissue
Authors: Kimble Amy L. , Silva Jordan , Murphy Melissa , Hensel Jessica A. , Nicholas Sarah-Anne E. , Jellison Evan R. , Reese Bo , Murphy Patrick A.
Published: May 2021

Endothelial cells are important contributors to brain development, physiology, and disease. Although RNA sequencing has contributed to the understanding of brain endothelial cell diversity, bulk analysis and single-cell approaches have relied on fresh tissue digestion protocols for the isolation of single endothelial cells and flow cytometry-based sorting on surface markers or transgene expression. These approaches are limited in the analysis of the endothelium in human brain tissues, where fresh samples are difficult to obtain. Here, we developed an approach to examine endothelial RNA expression by using an endothelial-specific marker to isolate nuclei from abundant archived frozen brain tissues. We show that this approach rapidly and reliably extracts endothelial nuclei from frozen mouse brain samples, and importantly, from archived frozen human brain tissues. Furthermore, isolated RNA transcript levels are closely correlated with expression in whole cells from tissue digestion protocols and are enriched in endothelial markers and depleted of markers of other brain cell types. As high-quality RNA transcripts could be obtained from as few as 100 nuclei in archived frozen human brain tissues, we predict that this approach should be useful for both bulk analysis of endothelial RNA transcripts in human brain tissues as well as single-cell analysis of endothelial sub-populations.
A Randomized Placebo-Controlled Trial of Sarilumab in Hospitalized Patients with Covid-19
Authors: Sivapalasingam Sumathi , Lederer David J. , Bhore Rafia , Hajizadeh Negin , Criner Gerard , Hosain Romana , Mahmood Adnan , Giannelou Angeliki , Somersan-Karakaya Selin , O’Brien Meagan , Boyapati Anita , Parrino Janie , Musser Bret , Labriola-Tompkins Emily , Ramesh Divya , Purcell Lisa A. , Gulabani Daya , Kampman Wendy , Waldron Alpana , Gong Michelle Ng , Saggar Suraj , Sperber Steven J. , Menon Vidya , Stein David K. , Sobieszczyk Magdalena E. , Park William , Aberg Judith A. , Brown Samuel M. , Kosmicki Jack A. , Horowitz Julie E. , Ferreira Manuel A. , Baras Aris , Kowal Bari , DiCioccio A. Thomas , Akinlade Bolanle , Nivens Michael C. , Braunstein Ned , Herman Gary , Yancopoulos George D. , Weinreich David M. ,   for the Sarilumab-COVID-19 Study Team
Published: May 2021

BACKGROUND

Sarilumab (anti-interleukin-6 receptor-α monoclonal antibody) may attenuate the inflammatory response in Covid-19.

METHODS

We performed an adaptive, phase 2/3, randomized, double-blind, placebo-controlled trial of intravenous sarilumab 200 mg or 400 mg in adults hospitalized with Covid-19. The phase 3 primary analysis population (cohort 1) was patients with critical Covid-19 receiving mechanical ventilation (MV) randomized to sarilumab 400 mg or placebo. The primary end point for phase 3 was the proportion of patients with ≥1-point improvement in clinical status from baseline to day 22.

RESULTS

Four-hundred fifty-seven (457) and 1365 patients were randomized and treated in phases 2 and 3, respectively. Among phase 3 critical patients receiving MV (n=289; 34.3% on corticosteroids), the proportion with ≥1-point improvement in clinical status (alive not receiving MV) at day 22 was 43.2% in sarilumab 400 mg and 35.5% in placebo (risk difference [RD] +7.5%; 95% confidence interval [CI], –7.4 to 21.3; P=0.3261), representing a relative risk improvement of 21.7%. Day 29 all-cause mortality was 36.4% in sarilumab 400 mg versus 41.9% in placebo (RD –5.5%; 95% CI, –20.2 to 8.7; relative risk reduction 13.3%). In post hoc analyses pooling phase 2 and 3 critical patients receiving MV, the hazard ratio (HR) for death in sarilumab 400 mg compared with placebo was 0.76 (95% CI, 0.51 to 1.13) overall, improving to 0.49 (95% CI, 0.25 to 0.94) in patients receiving corticosteroids at baseline.

CONCLUSION

In hospitalized patients with Covid-19 receiving MV, numerical benefits with sarilumab did not achieve statistical significance, but benefit may be greater in patients receiving corticosteroids. A larger study is required to confirm this observed numerical benefit.

(ClinicalTrials.gov number, NCT04315298)
Measuring post-discharge socioeconomic and quality of life outcomes in trauma patients: A scoping review
Authors: David Siddarth , Roy Nobhojit , Solomon Harris , Lundborg Cecilia Stålsby , Wärnberg Martin Gerdin
Published: May 2021

Purpose

Managing trauma is a global public health challenge. Measuring post-discharge socioeconomic and quality-of-life outcomes can help better understand and reduce the consequences of trauma.

Methods

We performed a scoping review to map the existing research on post-discharge outcomes for trauma patients, irrespective of the country or setting in which the study was performed. The scoping review was conducted by searching six databases: MEDLINE, EMBASE, the Cochrane Library, Global Index Medicus, BASE, and Web of Science to identify all articles that report post-discharge socioeconomic or quality of life outcomes in trauma patients from 2009 to 2018.

Results

758 articles were included in this study, extracting 958 outcomes. Most studies (82%) were from high-income countries (HICs). More studies from low- and middle-income countries (LMICs) were cross-sectional (71%) compared with HIC settings (46%). There was a wide variety of different definitions, interpretations, and measurements used by various articles for similar outcomes. Quality of life, return to work, social support, cost, and participation were the main outcomes studied in post-discharge trauma patients.

Conclusions

The wide range of outcomes and outcome measures reported across different types of injuries and settings. This variability can be a barrier when comparing across different types of injuries and settings. Post-discharge trauma studies should move towards building evidence based on standardized measurement of outcomes.
Recovery from severe mental health problems: A systematic review of service user and informal caregiver perspectives
Authors: Vera San Juan Norha , Gronholm Petra C , Heslin Margaret , Lawrence Vanessa , Bain Matt , Okuma Ayako , Evans-Lacko Sara
Published: May 2021

Introduction

The recovery approach aims to have users’ perspectives at the heart of service development and research; it is a holistic perspective that considers social needs, personal growth and inclusion. In the last decade recovery-oriented research and practice has increased greatly, however, a comprehensive model of recovery considering exclusively the perspectives of people with lived experience has not been devised.

Aims

This review aimed to develop a framework and contextualise service users’ and informal caregivers’ understanding of recovery from severe mental health problems.

Methods

A systematic search of 6 databases including key terms related to knowledge, experience and narratives AND mental health AND personal recovery. The search was supplemented with reference sourcing through grey literature, reference tracking and expert consultation. Data analysis consisted of a qualitative meta-synthesis using constant comparative methods.

Results

Sixty-two studies were analysed. A pattern emerged regarding the recovery paradigms that the studies used to frame their findings. Recovery domains included Legal, political and economic recovery; Social recovery; Individual recovery; and Clinical recovery experience. Service users’ definitions of recovery tended to prioritise social aspects, particularly being accepted and connecting with others, while caregivers focused instead on clinical definitions of recovery such as symptom remission. Both groups emphasised individual aspects such as becoming self-sufficient and achieving personal goals, which was strongly linked with having economic means for independence.

Conclusions

The recovery model provided by this review offers a template for further research in the field and a guide for policy and practice. Predominant definitions of recovery currently reflect understandings of mental health which focus on an individual perspective, while this review found an important emphasis on socio-political aspects. At the same time, only a small number of studies took place in low-income countries, focused on minoritised populations, or included caregivers’ perspectives. These are important gaps in the literature that require further attention.

Visual abstract
Different approaches to quantify years of life lost from COVID-19
Authors: Ferenci Tamás
Published: May 2021

The burden of an epidemic is often characterized by death counts, but this can be misleading as it fails to acknowledge the age of the deceased patients. Years of life lost is therefore widely used as a more relevant metric, however, such calculations in the context of COVID-19 are all biased upwards: patients dying from COVID-19 are typically multimorbid, having far worse life expectation than the general population. These questions are quantitatively investigated using a unique Hungarian dataset that contains individual patient level data on comorbidities for all COVID-19 deaths in the country. To account for the comorbidities of the patients, a parametric survival model using 11 important long-term conditions was used to estimate a more realistic years of life lost. As of 12 May, 2021, Hungary reported a total of 27,837 deaths from COVID-19 in patients above 50 years of age. The usual calculation indicates 10.5 years of life lost for each death, which decreases to 9.2 years per death after adjusting for 11 comorbidities. The expected number of years lost implied by the life table, reflecting the mortality of a developed country just before the pandemic is 11.1 years. The years of life lost due to COVID-19x in Hungary is therefore 12% or 1.3 years per death lower when accounting for the comorbidities and is below its expected value, but how this should be interpreted is still a matter of debate. Further research is warranted on how to optimally integrate this information into epidemiologic risk assessments during a pandemic.
Localization and RNAi-driven inhibition of a Brugia malayi encoded Interleukin-5 Receptor Binding protein
Authors: Mejia Rojelio , Bennuru Sasisekhar , Oksov Yelena , Lustigman Sara , Munirathinam Gnanasekar , Kalyanasundaram Ramaswamy , Nutman Thomas B.
Published: May 2021

A molecule termed BmIL5Rbp (aka Bm8757) was identified from Brugia malayi filarial worms and found to competitively inhibit human IL-5 binding to its human receptor.

After the expression and purification of a recombinant BmIL5Rbp and generation of BmIL5Rbp-specific rabbit antibody, we localized the molecule on B. malayi worms through immunohistochemistry and immunoelectron microscopy. RNA interference was used to inhibit BmIL5Rbp mRNA and protein production. BmIL5Rbp was shown to localize to the cuticle of Brugia malayi and to be released in their excretory/secretory products. RNAi inhibited BmIL5Rbp mRNA production by 33% and reduced the surface protein expression by ~50% and suppressed the release of BmIL5Rbp in the excretory/secretory products. RNAi has been used successfully to knock down the mRNA and protein expression of BmIL5Rbp in the early larval stages of B. malayi and provided a proof-of-principle for the local inhibition of the human IL5 receptor. These findings provide evidence that a parasite encoded IL5R antagonist could be utilized therapeutically.
nGauge: Integrated and extensible neuron morphology analysis in Python
Authors: Walker Logan A , Williams Jennifer S , Li Ye , Roossien Douglas H , Michki Nigel S , Cai Dawen
Published: May 2021

The study of neuron morphology requires robust and comprehensive methods to quantify the differences between neurons of different subtypes and animal species. Several software packages have been developed for the analysis of neuron tracing results stored in the standard SWC format. However, providing relatively simple quantifications and their non-extendable architecture prohibit their use for advanced data analysis and visualization. We developed nGauge, a Python toolkit to support the parsing and analysis of neuron morphology data. As an application programming interface (API), nGauge can be referenced by other popular open-source software to create custom informatics analysis pipelines and advanced visualizations. nGauge defines an extendable data structure that handles volumetric constructions (e.g. soma), in addition to the SWC linear reconstructions, while remaining light-weight. This greatly extends nGauge’s data compatibility.
Truncating Tau Reveals Different Pathophysiological Actions of Oligomers in Single Neurons
Authors: Hill Emily , Karikari Thomas K. , Lantero-Rodriguez Juan , Zetterberg Henrik , Blennow Kaj , Richardson Magnus J , Wall Mark J
Published: May 2021

Tau protein is involved in maintaining neuronal structure. In Alzheimer’s disease, small numbers of tau molecules can aggregate to forms oligomers. However, how these oligomers produce changes in neuronal function remains unclear. Previously, oligomers made from full-length human tau were found to have multiple effects on neuronal properties. Here we have cut the tau molecule into two parts: the first 123 amino acids and the remaining 124-441 amino acids. These truncated tau molecules had specific effects on neuronal properties, allowing us to assign the actions of full-length tau to different regions of the molecule. We identified one key target for the effects of tau, the voltage gated sodium channel, which could account for the effects of tau on the action potential. By truncating the tau molecule, we have probed the mechanisms that underlie tau dysfunction, and this increased understanding of tau’s pathological actions, will build towards developing future tau-targeting therapies.
A Genome-Scale TF-DNA Interaction Network of Transcriptional Regulation of Arabidopsis Primary and Specialized Metabolism
Authors: Tang Michelle , Li Baohua , Zhou Xue , Bolt Tayah , Li Jia Jie , Cruz Neiman , Gaudinier Allison , Ngo Richard , Clark-Wiest Caitlin , Kliebenstein Daniel J. , Brady Siobhan M.
Published: May 2021

In single-celled microbes, transcriptional regulation by single transcription factors is sufficient to shift primary metabolism. Corresponding genome-level transcriptional regulatory maps of metabolism reveal the underlying design principles responsible for these shifts as a model in which master regulators largely coordinate specific metabolic pathways. Relative to individual microbes, plant metabolism is more complex. Primary and specialized metabolism occur within innumerable cell types, and their reactions shift depending on internal and external cues. Given the importance of plants and their metabolites in providing humanity with food, fiber and medicine, we set out to develop a genome-scale transcriptional regulatory map of Arabidopsis metabolic genes. A comprehensive set of protein-DNA interactions between Arabidopsis thaliana transcription factors and promoters of primary metabolism and specialized metabolism were mapped. To demonstrate the utility of this resource, we identified and functionally validated regulators of the TCA cycle. The resulting network suggests that plant metabolic design principles are distinct from that of microbes. Instead, metabolism appears to be transcriptionally coordinated via developmental- and stress-conditional processes that can coordinate across primary and specialized metabolism. These data represent the most comprehensive resource of interactions between TFs and metabolic genes in plants.
PEN receptor GPR83 in anxiety-like behaviors: differential regulation in global vs amygdalar knockdown
Authors: Fakira Amanda K. , Lueptow Lindsay M. , Trimbake Nikita A. , Devi Lakshmi A.
Published: May 2021

Anxiety disorders are prevalent across the United States and result in a large personal and societal burden. Currently, numerous therapeutic and pharmaceutical treatment options exist. However, drugs to classical receptor targets have shown limited efficacy and often come with unpleasant side effects, highlighting the need to identify novel targets involved in the etiology and treatment of anxiety disorders. GPR83, a recently deorphanized receptor activated by the abundant neuropeptide PEN, has also been identified as a glucocorticoid regulated receptor (and named GIR) suggesting that this receptor may be involved in stress-responses that underlie anxiety. Consistent with this, GPR83 null mice have been found to be resistant to stress-induced anxiety. However, studies examining the role of GPR83 within specific brain regions or potential sex differences have been lacking. In this study, we investigate anxiety-related behaviors in male and female mice with global knockout and following local GPR83 knockdown in female mice. We find that a global knockdown of GPR83 has minimal impact on anxiety-like behaviors in female mice and a decrease in anxiety-related behaviors in male mice. In contrast, a local GPR83 knockdown in the basolateral amygdala leads to more anxiety-related behaviors in female mice. Local GPR83 knockdown in the central amygdala or nucleus accumbens showed no significant effect on anxiety-related behaviors. Finally, dexamethasone administration leads to a significant decrease in receptor expression in the amygdala and nucleus accumbens of female mice. Together, our studies uncover a significant, but divergent role for GPR83 in different brain regions in the regulation of anxiety-related behaviors, which is furthermore dependent on sex.
Predicted the impacts of climate change and extreme-weather events on the future distribution of fruit bats in Australia
Authors: Diengdoh Vishesh L. , Ondei Stefania , Hunt Mark , Brook Barry W.
Published: May 2021

Aim

Fruit bats (Megachiroptera) are important pollinators and seed dispersers whose distribution might be affected by climate change and extreme-weather events. We assessed the potential impacts of those changes, particularly more frequent and intense heatwaves, and drought, on the future distribution of fruit bats in Australia. We also focus a case study on Tasmania, the southernmost island state of Australia, which is currently devoid of fruit bats but might serve as a future climate refugium.

Location

Australia (continental-scale study) and Tasmania.

Methods

Species distribution modelling was used to predict the occurrence of seven species of fruit bats, using an ensemble of machine-learning algorithms. Predictors included extreme-weather events (heatwave and drought), vegetation (as a proxy for habitat) and bioclimatic variables. Predictions were made for the current-day distribution and future (2050 and 2070) scenarios using multiple emission scenarios and global circulation models.

Results

Changes in climate and extreme-weather events are forecasted to impact all fruit-bat species, with the loss and gain of suitable areas being predominantly along the periphery of a species’ current distribution. A higher emission scenario resulted in a higher loss of areas for Grey-headed flying fox (Pteropus poliocephalus) and Spectacled flying fox (P. conspicillatus) but a higher gain of areas for the Northern blossom bat (Macroglossus minimus). The Grey-headed flying fox (Pteropus poliocephalus) is the only study species predicted to potentially occur in Tasmania under future scenarios.

Main conclusions

Fruit bats are likely to respond to climate change and extreme weather by migrating to more suitable areas, including regions not historically inhabited by those species such as Tasmania—possibly leading to human-wildlife conflicts. Conservation strategies (e.g., habitat protection) should focus on areas we found to remain suitable under future scenarios, and not be limited by state-political boundaries.
Robust and Remote Measurement of Heart Rate Based on A Surveillance Camera
Authors: Yang Yiming , Lian Chao , Zhang Hongyu , Li Liangjiang , Zhao Yuliang
Published: May 2021

Arrhythmia is a marked symptom of many cardiovascular diseases (CVDs). The accurate and timely detection of heart rate can greatly reduce the harm of arrhythmia to people. However, it is still a challenge to robustly and remotely measure heart rate in daily life due to the changing environmental conditions during measurement, such as the varying light intensity, the movement of people, and the uncertain distance between the sensor to people. In this study, we propose a method to accurately measure human heart rate within a distance of 4.5 meters under different light intensities by simply using a surveillance camera. After a 20-second color video of a person’s hand is captured by the camera, a method based on the Fast Fourier Transform (FFT) algorithm is designed to extract the blood volume pulse wave to calculate the heart rate. According to the comparison between the real heart rate and results measured by electrocardiography (ECG), the proposed method achieves an accuracy of 95.8% when the measurement is performed within a distance of 4.5 meters and 90% when within 5.0 meters. Our experiments show that when the illuminance varies between 100-1000 lux (lighting level indoor), we still get the correct results. Our experiments also demonstrate that the proposed method accurately obtain heart rate even when the light intensity is below 32 lux (300-500 lux in a workplace environment). The method’s strong adaptability to changing environmental conditions makes it applicable to many scenarios, such as homes of the elderly, classrooms, and other public spaces.
Thrombopoietin from hepatocytes promotes hematopoietic stem cell regeneration after myeloablation
Authors: Gao Longfei , Decker Matthew , Chen Haidee , Ding Lei
Published: May 2021

The bone marrow niche plays a critical role in hematopoietic recovery and hematopoietic stem cell (HSC) regeneration after myeloablation. However, it is not clear whether systemic factors beyond the local niche are required for these essential processes in vivo. Thrombopoietin (TPO) is a critical cytokine promoting hematopoietic rebound after myeloablation and its transcripts are expressed by multiple cellular sources. The upregulation of bone marrow-derived TPO has been proposed to be crucial for hematopoietic recovery and HSC regeneration after stress. Nonetheless, the cellular source of TPO in stress has never been investigated genetically. We assessed the functional sources of TPO following two common myeloablative perturbations: 5-fluorouracil (5-FU) administration and irradiation. Using a Tpo translational reporter, we found that the liver but not the bone marrow is the major source of TPO protein after myeloablation. Mice with conditional Tpo deletion from osteoblasts or bone marrow stromal cells showed normal recovery of HSCs and hematopoiesis after myeloablation. In contrast, mice with conditional Tpo deletion from hepatocytes showed significant defects in HSC regeneration and hematopoietic rebound after myeloablation. Thus, systemic TPO from the liver is necessary for HSC regeneration and hematopoietic recovery in myeloablative stress conditions.
Vector-borne Trypanosoma brucei parasites develop in artificial human skin and persist as skin tissue forms
Authors: Reuter Christian , Imdahl Fabian , Hauf Laura , Vafadarnejad Ehsan , Fey Philipp , Finger Tamara , Walles Heike , Saliba Antoine-Emmanuel , Groeber-Becker Florian , Engstler Markus
Published: May 2021

Transmission of Trypanosoma brucei by tsetse flies involves the deposition of the cell cycle-arrested metacyclic life cycle stage into mammalian skin at the site of the fly’s bite. In the skin, the metacyclic parasites reactivate and differentiate into proliferative trypanosomes before colonizing the host’s blood and tissues. We generated an advanced human skin equivalent and used tsetse flies to naturally infect the artificial skin with trypanosomes. We detailed the chronological order of the parasites’ development in the skin, and found a rapid activation of metacyclic trypanosomes and differentiation to proliferative parasites. Single-cell parasite transcriptomics were used to document the biological events during differentiation and host invasion at five different timepoints. After the establishment of a proliferative trypanosome population in the skin, the parasites entered a reversible quiescent state characterized by slow replication and a strongly reduced metabolism. We termed these quiescent trypanosomes skin tissue forms (STF), a parasite population that may play an important role in maintaining the infection over long time periods and in asymptomatic infected individuals.
Composition and Biophysical Properties of the Sorting Platform Pods in the Shigella Type III Secretion System
Authors: Tachiyama Shoichi , Skaar Ryan , Chang Yunjie , Carroll Brittany , Muthuramalingam Meenakumari , Whittier Sean K. , Barta Michael L. , Picking Wendy L. , Liu Jun , Picking William D.
Published: May 2021

Shigella flexneri, causative agent of bacillary dysentery (shigellosis), uses a type III secretion system (T3SS) as its primary virulence factor. The T3SS injectisome delivers effector proteins into host cells to promote entry and create an important intracellular niche. The injectisome’s cytoplasmic sorting platform (SP) is a critical assembly that contributes to substrate selection and energizing secretion. The SP consists of oligomeric Spa33 “pods” that associate with the basal body via MxiK and connect to the Spa47 ATPase via MxiN. The pods contain heterotrimers of Spa33 with one full-length copy associated with two copies of a C-terminal domain (Spa33C). The structure of Spa33C is known, but the precise makeup and structure of the pods in situ remains elusive. We show here that recombinant wild-type Spa33 can be prepared as a heterotrimer that forms distinct stable complexes with MxiK and MxiN. In two-hybrid analyses, association of the Spa33 complex with these proteins occurs via the full-length Spa33 component. Furthermore, these complexes each have distinct biophysical properties. Based on these properties, new high-resolution cryo-electron tomography data and architectural similarities between the Spa33 and flagellar FliM-FliN complexes, we provide a preliminary model of the Spa33 heterotrimers within the SP pods. From these findings and evolving models of SP interfaces and dynamics in the Yersinia and Salmonella T3SS, we suggest a model for SP function in which two distinct complexes come together within the context of the SP to contribute to form the complete pod structures during the recruitment of T3SS secretion substrates.
Mechanistic model: Analysis of diffusion dynamics of Lugol’s chromoendoscopy in Basal layer-type squamous cell carcinoma in situ via Euler’s method and Law of mass action
Authors: Xiong Fei
Published: May 2021

Basal layer-type squamous cell carcinoma in situ(BLSCC) is an aggressive malignancy tumor. In the past, it usually went ignored because its aggressive biological behavior is different from typical esophageal squamous cancer(SCC). For our mechanistic model, we analyzed diffusion dynamics of iodine stain in BLSCC with the help of Euler’s method. We used the law of mass action description of the forming process of the iodine-glycogen Complex. Based on the above analysis, our mechanistic model reveals that the efficacy of Lugol’s chromoendoscopy is determined by the thickness of the squamous epithelial cell layer, which contains glycogen granules, and the convection of the interpupillary capillary loop(IPCL). A further inference can be made: the unique histological structure of BLSCC suggests Lugol’s chromoendoscopy does not detect some components of it because these components neither break enough squamous epithelial cells which contain glycogen granules nor contain enough number of IPCL in a specific time frame. Besides, if our mechanistic model starting point is BLSCC and typical SCC share the same evolution path, we found both their cytoplasm tends to solid phase from the iodine diffusion dynamics analysis in “pink color sign.”
Understanding Microbeads Stacking in Deformable Nano-Sieve for Efficient Plasma Separation and Blood Cell Retrieval
Authors: Chen Xinye , Zhang Shuhuan , Gan Yu , Liu Rui , Wang Ruo-Qian , Du Ke
Published: May 2021

Efficient separation of blood cells and plasma is key for numerous molecular diagnosis and therapeutics applications. Despite various microfluidics-based separation strategies have been developed, a simple, reliable, and multiplexing separation device that can process a large volume of blood is still missing. Here we show a microbead packed deformable microfluidic system that can efficiently separate highly purified plasma from whole blood as well as retrieve blocked blood cells from the device. Combining microscope imaging, optical tomography scanning, and computational fluidic modeling, a highly accurate model is constructed to understand the link between the mechanical properties of the microfluidics, flow rate, and microbeads packing/leaking, which supports and rationalizes the experimental observations. This deformable nano-sieve device establishes a key technology for centrifuge-free diagnosis and treatment of bloodborne diseases and may be important for the design of next-generation deformable microfluidics for separation applications.