bluuebunny/crossref_metadata_2025 huggingface dataset:
Fibromyalgia in Axial Spondyloarthritis
Authors: Son Seung Min , Kim Dong Suk , Lee Jung Sub
Published: December 2020

Objectives

This study aimed to compare the demographic characteristics, disease activity, functional status, and quality of life between patients with axial spondyloarthritis and fibromyalgia and patients with axial spondyloarthritis without fibromyalgia.

Methods

We searched MEDLINE via PubMed, Cochrane, Scopus, and Embase databases, from the earliest available indexing date to March 30, 2019, for comparative studies evaluating fibromyalgia in patients with axial spondyloarthritis. Two authors extracted data independently, and all discrepancies were resolved through consensus.

Results

Seven comparative studies were identified. No statistically significant differences were observed in terms of age, levels of inflammatory markers, and prevalence of extra-articular manifestations such as uveitis, psoriasis, and inflammatory bowel disease between patients with Axial spondyloarthritis fibromyalgia and those without it. Sex ratios (female to male) were approximately 3:2 and 1:3 in patients with and without fibromyalgia, respectively. The ratios concerning human leukocyte antigen B27–positive patients with and without fibromyalgia were 45.1% and 65.6%, respectively. Patients with fibromyalgia had significantly higher Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, and Ankylosing Spondylitis Quality of Life scores.

Conclusions

Our meta-analysis showed that patients with Axial spondyloarthritis fibromyalgia had considerably higher pain severity, disease activity, and worse quality of life than patients without fibromyalgia. The sex ratios (female to male) were approximately 3:2 and 1:3, and ratios for human leukocyte antigen B27–positive patients were 45.1% and 65.6% in patients with and without fibromyalgia, respectively. Further well-designed studies are needed to substantiate our results.
High Prevalence of Metabolic Syndrome in Patients With Psoriatic Arthritis From Northeastern Brazil
Authors: Adeodato Ramos Lysiane Maria , Gomes Kirla Wagner Poti , de Saboia Mont'Alverne Andrea Rocha , Braga Marcio Vale , Costa Vasconcelos Antonio Helder , Rodrigues Carlos Ewerton Maia
Published: December 2020

Background

Metabolic syndrome (MetS) causes morbidity in patients with psoriatic arthritis (PsA).

Objective

The aims of this cross-sectional study were to evaluate the prevalence of MetS in PsA patients compared with sex- and age-matched healthy controls and to test possible associations with clinical and laboratory variables.

Methods

The prevalence of MetS was determined for 76 PsA patients and 76 sex- and age-matched healthy controls, using the criteria of NCEP/ATPIII and Harmonizing, adjusted for South Americans. Multivariate logistic regression analysis was used to identify independent risk factors for MetS.

Results

Metabolic syndrome was significantly more prevalent in the PsA group than in the control group (53.9% vs 18.4%, p < 0.001). Psoriatic arthritis was associated with hypertension, diabetes mellitus, increased waist circumference (WC), elevated body mass index, and raised levels of blood glucose and triglycerides. When comparing MetS and non-Mets PsA patients, MetS was not significantly associated with disease activity, skin involvement, or quality of life. In the logistic regression model, the variables independently associated with MetS were use of biologic disease-modifying antirheumatic drugs (p = 0.001), elevated arterial pressure (p = 0.006), age (p = 0.0015), WC (p = 0.004), and low HDL (p = 0.042).

Conclusions

In this study on PsA patients from Northeastern Brazil, MetS was highly prevalent and associated with biologic disease-modifying antirheumatic drugs use, increased WC, and low HDL.
Development and Validation of an Age-Appropriate Website for Children Requiring Clean Intermittent Catheterization
Authors: de Avila Marla Andréia Garcia , Rabello Thaís , de Araújo Maria Paula Bortoleti , Amaro João Luiz , Zornoff Denise de Cássia Moreira , Ferreira Ana Silvia Sartori Barraviera Seabra , de Oliveira Ananda Stefani
Published: December 2020

Purpose

This study describes the development and validation of an age-appropriate website for preschool children who require clean intermittent catheterization (CIC).

Methods

An age-appropriate website was developed at an academic medical center in Brazil and included child-friendly characters, details of the urinary system anatomy and physiology, hand-washing, and the CIC procedure. Content was validated by physicians, nurses, and health informatics professionals. Face validity was assessed by parents.

Findings

Content and face validity indices were 0.94 and 0.92, respectively.

Conclusions

The free website (www.doutorbexiga.com.br) was successfully validated and considered suitable and user-friendly for the health education of children requiring CIC.

Clinical Relevance

Physicians and nurses can use the website as a model for developing similar materials. The website can be a resource for health professionals and parents of children with spinal cord injury or other neurological disorders to encourage children to learn about CIC through animated educational materials.
Cardiac Magnetic Resonance Imaging in Coronavirus Disease 2019 (COVID-19)
Authors: Ojha Vineeta , Verma Mansi , Pandey Niraj N. , Mani Avinash , Malhi Amarinder S. , Kumar Sanjeev , Jagia Priya , Roy Ambuj , Sharma Sanjiv
Published: December 2020

Objective:

Cardiac magnetic resonance imaging (CMR) with its new quantitative mapping techniques has proved to be an essential diagnostic tool for detecting myocardial injury associated with coronavirus disease 2019 (COVID-19) infection. This systematic review sought to assess the important imaging features on CMR in patients diagnosed with COVID-19.

Materials and Methods:

We performed a systematic literature review within the PubMed, Embase, Google Scholar, and WHO databases for articles describing the CMR findings in COVID-19 patients.

Results:

A total of 34 studies comprising 199 patients were included in the final qualitative synthesis. Of the CMRs 21% were normal. Myocarditis (40.2%) was the most prevalent diagnosis. T1 (109/150; 73%) and T2 (91/144; 63%) mapping abnormalities, edema on T2/STIR (46/90; 51%), and late gadolinium enhancement (LGE) (85/199; 43%) were the most common imaging findings. Perfusion deficits (18/21; 85%) and extracellular volume mapping abnormalities (21/40; 52%), pericardial effusion (43/175; 24%), and pericardial LGE (22/100; 22%) were also seen. LGE was most commonly seen in the subepicardial location (81%) and in the basal-mid part of the left ventricle in inferior segments. In most of the patients, ventricular functions were normal. Kawasaki-like involvement with myocardial edema without necrosis/LGE (4/6; 67%) was seen in children.

Conclusion:

CMR is useful in assessing the prevalence, mechanism, and extent of myocardial injury in COVID-19 patients. Myocarditis is the most common imaging diagnosis, with the common imaging findings being mapping abnormalities and myocardial edema on T2, followed by LGE. As cardiovascular involvement is associated with poor prognosis, its detection warrants prompt attention and appropriate treatment.
Advanced age heightens hepatic damage in a murine model of scald burn injury
Authors: Idrovo Juan-Pablo , Boe Devin M. , Kaahui Soncy , Walrath Travis , McMahan Rachel H. , Kovacs Elizabeth J.
Published: December 2020

BACKGROUND

Elderly burn patients exhibit a lower survival rate compared with younger counterparts. The liver is susceptible to damage after burn injury, which predisposes to poor outcomes. Lipid homeostasis and the antioxidant glutathione system play fundamental roles in preserving liver integrity. Herein, we explored changes in these major pathways associated with liver damage in the aging animals after burn injury.

METHODS

We compared liver enzymes, histology, lipid-peroxidation, and glutathione-metabolism profiles from young and aged female mice after a 15% total body surface area burn. Mice were euthanized at 24 hours after injury, and livers and serum were collected.

RESULTS

Aged burn animals exhibited elevated (p < 0.05) aspartate aminotransferase and alanine aminotransferase levels and increased inflammatory cell infiltration, edema, and necrosis compared with their younger counterparts. The percentage of adipophilin-stained area in livers from young sham, young burn, aged sham, and aged burn groups was 10%, 44%, 16%, and 78% (p < 0.05), respectively. Liver malondialdehyde levels were 1.4 ± 0.5 nmol/mg, 2.06 ± 0.2 nmol/mg, 1.81 ± 0.12 nmol/mg, and 3.45 ± 0.2 nmol/mg (p < 0.05) in young sham, young burn, aged sham, and aged burn mice, respectively. Oxidized glutathione (GSSG) content increased 50% in the young burn, and 88% in aged burn animals compared with the young sham group (p < 0.05). The reduced glutathione GSH/GSSG ratio was significantly reduced by 54% in aged burn mice compared with young sham animals (p < 0.05). Furthermore, glutathione peroxidase gene expression showed a 96% decrease in the aged burn group compared with young sham mice (p < 0.05).

CONCLUSION

Aged burn animals exhibit severe liver damage from heightened lipid peroxidation and inadequate antioxidative response. The increased peroxidation is associated with abundant lipid deposits in hepatic tissue postburn and a weak antioxidative response due to hepatic glutathione peroxidase downregulation. Further studies will focus on the functional significance of these findings concerning hepatic homeostasis.
“We tend to get pad happy”: a qualitative study of health practitioners’ perspectives on continence care for older people in hospital
Authors: Percival John , Abbott Katharine , Allain Theresa , Bradley Rachel , Cramp Fiona , Donovan Jenny , McCabe Candy , Neubauer Kyra , Redwood Sabi , Cotterill Nikki
Published: December 2020

Background

Bladder and bowel control difficulties affect twenty and ten per cent of the UK population respectively, touch all age groups and are particularly prevalent in the older (65+) population. However, the quality of continence care is often poor, compromising patient health and wellbeing, increasing the risk of infection and is a predisposing factor to nursing and residential home placement.

Objective

To identify factors that help or hinder good continence care in hospital.

Methods

We conducted 27 qualitative interviews with nursing, medical and allied health practitioners in three hospitals. We used a purposive sample and analysed data thematically, both manually and with the aid of NVivo software.

Results

Interviews revealed perspectives on practice promoting or inhibiting good quality continence care, as well as suggestions for improvements. Good continence care was said to be advanced through person-centred care, robust assessment and monitoring, and a proactive approach to encouraging patient independence. Barriers to quality care centred on lack of oversight, automatic use of incontinence products and staffing pressures. Suggested improvements centred on participatory care, open communication and care planning with a higher bladder and bowel health profile. In order to drive such improvements, hospital-based practitioners indicate a need and desire for regular continence care training.

Conclusions

Findings help explain the persistence of barriers to providing good quality care for patients with incontinence. Resolute continence promotion, in hospitals and throughout the NHS, would reduce reliance on products and the accompanying risks of patient dependency and catheter associated gram negative bacteraemia. Robust assessment and care planning, open communication and regular continence care training would assist such promotion and also help mitigate resource limitations by developing safer, time-efficient continence care.
Theoretical Epidemic Laws Based on Data of COVID-19 Pandemic
Authors: Guo Junke
Published: December 2020

The standard growth model of epidemic evolution such as the Richards generalized logistic function is remarkably successful because it agrees with almost all previous epidemic data. Yet, it fails to explain intervention measures for mitigations of the ongoing coronavirus 2019 disease (COVID-19) pandemic. It also fails to replicate an endemic phase that occurs in many countries epidemic curves (time series data of daily new cases). These discrepancies demonstrate that new epidemic laws are required to understand, predict and mitigate the COVID-19 pandemic. Here we show that almost all COVID-19 evolution can be modeled by three innovative epidemic laws. Specifically, based on the world COVID-19 data, we first divide an epidemic curve into three phases: an exponential growth phase, an exponential decay phase, and a constant endemic phase. We next integrate the growth and the decay phases into the first epidemic law with interventions as a model parameter. This law is completely opposite to the Richards generalized logistic function in terms of intervention measures. We then combine the first epidemic law with the endemic phase to form the second epidemic law, which makes the curve of cumulative cases increase linearly as time tends to infinity. The third epidemic law states if an epidemic is composed of multiple epidemic waves, the superposition principle applies. These laws were confirmed by the COVID-19 data from 18 countries including undeveloped, developing and developed countries. Finally, we pave the way for future research to incorporate the proposed theory into the classic SIR model. We anticipate that the results from this research can provide a scientific base for governments to mitigate the COVID-19 and other epidemic disasters.
THE DUAL-TASK COST IS DUE TO NEURAL INTERFERENCES DISRUPTING THE OPTIMAL SPATIO-TEMPORAL DYNAMICS OF THE COMPETING TASKS
Authors: Mac-Auliffe Diego , Chatard Benoit , Petton Mathilde , Croizé Anne-Claire , Sipp Florian , Bontemps Benjamin , Gannerie Adrien , Bertrand Olivier , Rheims Sylvain , Kahane Philippe , Lachaux Jean-Philippe
Published: December 2020

Dual-tasking is extremely prominent nowadays, despite ample evidence that it comes with a performance cost: the Dual-Task (DT) cost. Neuroimaging studies have established that tasks are more likely to interfere if they rely on common brain regions, but the precise neural origin of the DT cost has proven elusive so far, mostly because fMRI does not record neural activity directly and cannot reveal the key effect of timing, and how the spatio-temporal neural dynamics of the tasks coincide.

Recently, DT electrophysiological studies in monkeys have recorded neural populations shared by the two tasks with millisecond precision to provide a much finer understanding of the origin of the DT cost. We used a similar approach in humans, with intracranial EEG, to assess the neural origin of the DT cost in a particularly challenging naturalistic paradigm which required accurate motor responses to frequent visual stimuli (task T1) and the retrieval of information from long-term memory (task T2), as when answering passengers’ questions while driving.

We found that T2 elicited neuroelectric interferences in the gamma-band (>40 Hz), in key regions of the T1 network including the Multiple Demand Network. They reproduced the effect of disruptive electrocortical stimulations to create a situation of dynamical incompatibility, which might explain the DT cost. Yet, participants were able to flexibly adapt their strategy to minimize interference, and most surprisingly, reduce the reliance of T1 on key regions of the executive control network – the anterior insula and the dorsal anterior cingulate cortex – with no performance decrement.

HIGHLIGHTS

- First direct evidence in humans of neural interferences between two tasks.

- First explanation of the Dual-Task cost at the neural level in humans.

- First Dual-Tasking study with intracranial EEG in naturalistic conditions.
Linkage disequilibrium under polysomic inheritance
Authors: Huang Kang , Dunn Derek W. , Li Wenkai , Wang Dan , Li Baoguo
Published: December 2020

The influence of genetic drift on linkage disequilibrium in finite populations has been extensively studied in diploids. However, to date the effects of ploidy on LD has not been extensively studied. We here extend the linkage disequilibrium measureDand Burrow’s Δ statistic to include polysomic inheritance, as well as their corresponding squared correlation coefficientsr2and, where the former is for phased genotypes and the latter for unphased genotypes. Weir & Hill’s double non-identity framework is also extended to include polysomic inheritance, and the expressions of double non-identity coefficients are derived under five mating systems. On this basis, the approximated expectations of estimatedr2andat equilibrium state,d2andδ2, are derived under five mating systems. We assess the behaviors of the estimatedr2andand the influence of the recombination rate ond2orδ2, simulate the application of estimating effective population size, and evaluate the statistical performance of the method of estimating.
The genetic case for cardiorespiratory fitness as a clinical vital sign and the routine prescription of physical activity in healthcare
Authors: Hanscombe Ken B. , Persyn Elodie , Traylor Matthew , Glanville Kylie P. , Hamer Mark , Coleman Jonathan R. I. , Lewis Cathryn M.
Published: December 2020

Background

Cardiorespiratory fitness (CRF) and physical activity (PA) are well-established predictors of morbidity and all-cause mortality. However, CRF is not routinely measured and PA not routinely prescribed as part of standard healthcare. The American Heart Association (AHA) recently presented a scientific case for the inclusion of CRF as a clinical vital sign based on epidemiological and clinical observation. Here, we leverage genetic data in the UK Biobank (UKB) to strengthen the case for CRF as a vital sign, and make a case for the prescription of PA.

Methods

We derived two CRF measures from the heart rate data collected during a submaximal cycle ramp test: CRF-vo2max, an estimate of the participants’ maximum volume of oxygen uptake, per kilogram of body weight, per minute; and CRF-slope, an estimate of the rate of increase of heart rate during exercise. Average PA over a 7-day period was derived from a wrist-worn activity tracker. After quality control, 70,783 participants had data on the two derived CRF measures, and 89,683 had PA data. We performed genome-wide association study (GWAS) analyses by sex, and post-GWAS techniques to understand genetic architecture of the traits and prioritize functional genes for follow-up.

Results

We found strong evidence that genetic variants associated with CRF and PA influenced genetic expression in a relatively small set of genes in heart, artery, lung, skeletal muscle, and adipose tissue. These functionally relevant genes were enriched among genes known to be associated with coronary artery disease (CAD), type 2 diabetes (T2D), and Alzheimer’s disease (three of the top 10 causes of death in high-income countries) as well as Parkinson’s disease, pulmonary fibrosis, and blood pressure, heart rate, and respiratory phenotypes. Genetic variation associated with lower CRF and PA was also correlated with several disease risk factors (including greater body mass index, body fat and multiple obesity phenotypes); a typical T2D profile (including higher insulin resistance, higher fasting glucose, impaired beta-cell function, hyperglycaemia, hypertriglyceridemia); increased risk for CAD and T2D; and a shorter lifespan.

Conclusions

Genetics supports three decades of evidence for the inclusion of CRF as a clinical vital sign. Given the genetic, clinical, and epidemiological evidence linking CRF and PA to increased morbidity and mortality, regular measurement of CRF as a marker of health and routine prescription of PA could be a prudent strategy to support public health.
Stress-related emotional and behavioural impact following the first COVID-19 outbreak peak
Authors: Benjamin Asaf , Kuperman Yael , Eren Noa , Amitai Maya , Rossman Hagai , Shilo Smadar , Meir Tomer , Keshet Ayya , Shwartz Orit Nuttman , Segal Eran , Chen Alon
Published: December 2020

Background

The coronavirus disease 2019 (COVID-19) pandemic poses multiple psychologically-stressful challenges and is associated with increased risk for mental illness. Previous studies have mostly focused on the psychopathological symptoms associated with the outbreak peak.

Methods

We examined the behavioural and mental health impact of the pandemic in Israel using an online survey. We collected 12,125 responses from 4,933 adult respondents during six weeks encompassing the end of the first outbreak and the beginning of the second. We used clinically validated instruments (Brief Symptom Inventory 18 (BSI-18), Perceived stress scale (PSS), Brief COPE inventory) to assess anxiety- and depression-related emotional distress, symptoms, and coping strategies, as well as questions designed to specifically assess COVID-19-related concerns.

Results

Respondents indicated worrying more about the situation in their country and their close ones contracting the virus, than about their own health and financial situation. The reported distress correlates with the number of new COVID-19 cases and higher emotional burden was associated with being female, younger, unemployed, living in low socioeconomic status localities, encountering more people, and experiencing physiological symptoms. Unexpectedly, older age and having a prior medical condition were associated with reduced emotional distress.

Conclusions

Our findings show that inequalities in mental-health burden associated with the COVID-19 pandemic are relevant also following the initial outbreak, and highlight the environmental context and its importance in understanding individual ability to cope with the long-term stressful challenges of the pandemic.
A Selective Increase in OC Symptoms is Driving Information Seeking and Guideline Adherence During the Covid-19 Pandemic
Authors: Loosen Alisa M. , Skvortsova Vasilisa , Hauser Tobias U.
Published: December 2020

Background

Increased mental health problems as a reaction to stressful life events, such as the Covid-19 pandemic, are common. Critically, successful adaptation helps reduce such symptoms to baseline, preventing long-term psychiatric disorders. It is thus important to understand whether and which psychiatric symptoms only show transient elevations, and which persist long-term and become chronically heightened. At particular risk for the latter trajectory are disorders with symptoms directly affected by the pandemic, such as obsessive-compulsive disorder.

Methods

In this longitudinal large-scale study (N=416), we assessed how obsessive-compulsive (OC), anxiety, and depression symptoms changed throughout the course of the first pandemic wave in a sample of the general UK public. We further examined how these symptoms affected pandemic-related information seeking and adherence to governmental guidelines.

Findings

All psychiatric domains were initially elevated, but showed distinct adaptation patterns. Depression scores decreased during the first pandemic wave, however, OC symptoms further increased, even after the end of lockdown. These OC symptoms were directly linked to Covid-related information seeking which gave rise to higher adherence to government guidelines.

Interpretation

The rise and persistence of OC symptoms, despite the ease of Covid-19 restrictions, shows that OCD is disproportionally and chronically affected by the pandemic. This is particularly worrying with regards to the long-term impact of the Covid-19 pandemic on public mental health and indicates that patients with OCD may require particular treatment efforts.
A common 1.6 Mb Y-chromosomal inversion predisposes to subsequent deletions and severe spermatogenic failure in humans
Authors: Hallast Pille , Kibena Laura , Punab Margus , Arciero Elena , Rootsi Siiri , Grigorova Marina , Flores Rodrigo , Jobling Mark A. , Poolamets Olev , Pomm Kristjan , Korrovits Paul , Rull Kristiina , Xue Yali , Tyler-Smith Chris , Laan Maris
Published: December 2020

Male infertility is a prevalent condition, concerning 5-10% of men. So far, only some recurrent genetic factors have been described as confident contributors to spermatogenic failure. Here, we report the first re-sequencing study of the Y-chromosomalAzoospermia Factor c(AZFc) region combined with gene dosage and Y-haplogroup determination. In analysing 2,324 Estonian men, we uncovered a novel structural variant as a high-penetrant risk factor to male infertility. The Y lineage R1a1-M458, reported at >20% frequency in several European populations, carries a fixed ∼1.6 Mb longr2/r3inversion destabilizing theAZFcregion and predisposing to recurrent microdeletions. Such complex rearrangements were significantly enriched among severe oligozoospermia cases. The carriervsnon-carrier risk to spermatogenic failure was increased 8.6-fold (p= 6.0 × 10−4). The finding contributes to improved molecular diagnostics and clinical management of infertility. Carrier identification in young age will facilitate timely counselling and reproductive decision-making.
Ligand-receptor promiscuity enables cellular addressing
Authors: Su Christina J. , Murugan Arvind , Linton James M. , Yeluri Akshay , Bois Justin , Klumpe Heidi , Antebi Yaron E. , Elowitz Michael B.
Published: December 2020

In multicellular organisms, secreted ligands selectively activate, or “address,” specific target cell populations to control cell fate decision-making and other processes. Key cell-cell communication pathways use multiple promiscuously interacting ligands and receptors, provoking the question of how addressing specificity can emerge from molecular promiscuity. To investigate this issue, we developed a general mathematical modeling framework based on the bone morphogenetic protein (BMP) pathway architecture. We find that promiscuously interacting ligand-receptor systems allow a small number of ligands, acting in combinations, to address a larger number of individual cell types, each defined by its receptor expression profile. Promiscuous systems outperform seemingly more specific one-to-one signaling architectures in addressing capacity. Combinatorial addressing extends to groups of cell types, is robust to receptor expression noise, grows more powerful with increasing receptor multiplicity, and is maximized by specific biochemical parameter relationships. Together, these results identify fundamental design principles governing cell addressing by ligand combinations.
Structural basis of the protochromic green/red photocycle of the chromatic acclimation sensor RcaE
Authors: Nagae Takayuki , Unno Masashi , Koizumi Taiki , Miyanoiri Yohei , Fujisawa Tomotsumi , Masui Kento , Kamo Takanari , Wada Kei , Eki Toshihiko , Ito Yutaka , Hirose Yuu , Mishima Masaki
Published: December 2020

Cyanobacteriochromes (CBCRs) are bilin-binding photosensors of the phytochrome superfamily that show remarkable spectral diversity. The green/red CBCR subfamily is important for regulating chromatic acclimation of photosynthetic antenna in cyanobacteria and is applied for optogenetic control of gene expression in synthetic biology. They are suggested to combine the bilin C15-Z/C15-Ephotoisomerization with a change in the bilin protonation state to drive their absorption changes. However, structural information and direct evidence of the bilin protonation state are lacking. Here we report a high-resolution (1.63Å) crystal structure of the bilin-binding domain of the chromatic acclimation sensor RcaE in the red-absorbing photoproduct state. The bilin is buried within a “pan” consisting of hydrophobic residues, where the bilin configuration/conformation is C5-Z,syn/C10-Z,syn/C15-E,synwith the A–C rings co-planar and the D-ring tilted. Three pyrrole nitrogens of the A–C rings are covered in the α-face with a hydrophobic lid of Leu249 influencing the bilin pKa, whereas they are directly hydrogen-bonded in the β-face with the carboxyl group of Glu217. Glu217 is further connected to a cluster of waters forming a hole in the pan, which are in exchange with solvent waters in molecular dynamics simulation. We propose that the “holey pan” structure functions as a proton-exit/influx pathway upon photoconversion. NMR analysis demonstrated that the four pyrrole nitrogen atoms are indeed fully protonated in the red-absorbing state, but one of them, most likely the B-ring nitrogen, is deprotonated in the green-absorbing state. These findings deepen our understanding of the diverse spectral tuning mechanisms present in CBCRs.

Significance Statement

Green/red CBCRs are one of the most important CBCR subfamilies owing to their physiological roles in cyanobacteria phylum and optogenetic applications. They are known to utilize a change in the bilin protonation state to drive the marked change in green/red absorption, but the structural basis of the protochromic green/red photocycle are not well understood. Here, we have determined the crystal structure of the chromatic acclimation sensor RcaE of this subfamily in the photoproduct state, demonstrating a unique conformation of the bilin and its interacting residues. In addition, we provide direct evidence of the protonation state of the bilin via NMR analysis. These findings bring insight to our understanding of the molecular mechanisms underlying the spectral diversity of CBCRs.
Pre-existing T cell-mediated cross-reactivity to SARS-CoV-2 cannot solely be explained by prior exposure to endemic human coronaviruses
Authors: Tan Cedric C.S. , Owen Christopher J. , Tham Christine Y.L. , Bertoletti Antonio , van Dorp Lucy , Balloux Francois
Published: December 2020

Several studies have reported the presence of pre-existing humoral or cell-mediated cross-reactivity to SARS-CoV-2 peptides in healthy individuals unexposed to SARS-CoV-2. In particular, the current literature suggests that this pre-existing cross-reactivity could, in part, derive from prior exposure to ‘common cold’ endemic human coronaviruses (HCoVs). In this study, we characterised the sequence homology of SARS-CoV-2-derived T-cell epitopes reported in the literature across the entire diversity of theCoronaviridaefamily. Slightly over half (54.8%) of the tested epitopes did not have noticeable homology to any of the human endemic coronaviruses (HKU1, OC43, NL63 and 229E), suggesting prior exposure to these viruses cannot explain the full cross-reactive profiles observed in healthy unexposed individuals. Further, we find that the proportion of cross-reactive SARS-CoV-2 epitopes with noticeable sequence homology is extremely well predicted by the phylogenetic distance to SARS-CoV-2 (R2= 96.6%). None of the coronaviruses sequenced to date showed a statistically significant excess of T-cell epitope homology relative to the proportion of expected random matches given the sequence similarity of their core genome to SARS-CoV-2. Taken together, our results suggest that the repertoire of cross-reactive epitopes reported in healthy adults cannot be primarily explained by prior exposure to any coronavirus known to date, or any related yet-uncharacterised coronavirus.
DIAproteomics: A multi-functional data analysis pipeline for data-independent-acquisition proteomics and peptidomics
Authors: Bichmann Leon , Gupta Shubham , Rosenberger George , Kuchenbecker Leon , Sachsenberg Timo , Alka Oliver , Pfeuffer Julianus , Kohlbacher Oliver , Röst Hannes
Published: December 2020

Data-independent acquisition (DIA) is becoming a leading analysis method in biomedical mass spectrometry. Main advantages include greater reproducibility, sensitivity and dynamic range compared to data-dependent acquisition (DDA). However, data analysis is complex and often requires expert knowledge when dealing with large-scale data sets. Here we present DIAproteomics a multi-functional, automated high-throughput pipeline implemented in Nextflow that allows to easily process proteomics and peptidomics DIA datasets on diverse compute infrastructures. Central components are well-established tools such as the OpenSwathWorkflow for DIA spectral library search and PyProphet for false discovery rate assessment. In addition, it provides options to generate spectral libraries from existing DDA data and carry out retention time and chromatogram alignment. The output includes annotated tables and diagnostic visualizations from statistical post-processing and computation of fold-changes across pairwise conditions, predefined in an experimental design. DIAproteomics is open-source software and available under a permissive license to the scientific community athttps://www.openms.de/diaproteomics/.
A broadly resolved molecular phylogeny of New Zealand cheilostome bryozoans as a framework for hypotheses of morphological evolution
Authors: Orr RJS , Di Martino E , Gordon DP , Ramsfjell MH , Mello HL , Smith AM , Liow LH
Published: December 2020

Larger molecular phylogenies based on ever more genes are becoming commonplace with the advent of cheaper and more streamlined sequencing and bioinformatics pipelines. However, many groups of inconspicuous but no less evolutionarily or ecologically important marine invertebrates are still neglected in the quest for understanding species- and higher-level phylogenetic relationships. Here, we alleviate this issue by presenting the molecular sequences of 165 cheilostome bryozoan species from New Zealand waters. New Zealand is our geographic region of choice as its cheilostome fauna is taxonomically, functionally and ecologically diverse, and better characterized than many other such faunas in the world. Using this most taxonomically broadly-sampled and statistically-supported cheilostome phylogeny comprising 214 species, when including previously published sequences, we tested several existing systematic hypotheses based solely on morphological observations. We find that lower taxonomic level hypotheses (species and genera) are robust while our inferred trees did not reflect current higher-level systematics (family and above), illustrating a general need for the rethinking of current hypotheses. To illustrate the utility of our new phylogeny, we reconstruct the evolutionary history of frontal shields (i.e., a calcified bodywall layer in ascus-bearing cheilostomes) and asked if its presence has any bearing on the diversification rates of cheilostomes.
HDLs extract lipophilic drugs from cells
Authors: Zheng Adi , Dubuis Gilles , Ferreira Carla Susana Mendes , Mercier Thomas , Decosterd Laurent , Widmann Christian
Published: December 2020

High-density lipoproteins (HDLs) prevent cell death induced by a variety of cytotoxic drugs. The underlying mechanisms are however still poorly understood. Here we present evidence that HDLs efficiently protect cells against thapsigargin (a SERCA inhibitor) by extracting the drug from cells. Drug efflux could also be triggered to some extent by low-density lipoproteins (LDLs) and serum, which contains lipoproteins. HDLs did not reverse the non-lethal mild endoplasmic reticulum (ER) stress response induced by low thapsigargin concentrations or by SERCA knock-down but HDLs inhibited the toxic SERCA-independent effects mediated by high thapsigargin concentrations. HDLs were also found to extract other lipophilic compounds, such as the anti-diabetic drug glibenclamide. In contrast, hydrophilic substances (doxorubicin hydrochloride, rhodamine 123) were not extracted from cells by HDLs. This work shows that HDLs utilize their capacity of loading themselves with lipophilic compounds, akin to their ability to extract cellular cholesterol, to reduce the cell content of hydrophobic drugs. Silencing of the P-glycoprotein/ABCB1 transporter reduced the capacity of cells to load thapsigargin on HDLs. This work suggests that HDL-mediated cell efflux of toxic lipophilic xenobiotic is beneficial but also that HDL-mediated efflux can be detrimental to the therapeutic benefit of lipophilic drugs such as glibenclamide. Lipoprotein-mediated drug efflux should therefore be considered when evaluating drug efficacy.
Genomic analyses reveal FoxG as an upstream regulator ofwnt1required for posterior identity specification in planarians
Authors: Pascual-Carreras E. , Marín-Barba M. , Castillo-Lara S. , Coronel-Córdoba P. , Magri M.S. , Wheeler G.N. , Abril J.F. , Gomez-Skarmeta J.L. , Saló E. , Adell T.
Published: December 2020

Embryonic specification of the first body axis requires the formation of an Organizer, a group of cells with the ability to instruct fates in the surrounding tissue. The existence of organizing regions in adults, i.e. during regeneration, which also requires patterning of new tissues, remains unstudied. To that aim, we study regeneration in planarians, flatworms that can regenerate any missing structure, even the head, in a few days. In planarians, as described in embryonic models, the cWNT pathway specifies the anterior-posterior axis. During the first 12-24h after amputation bothwnt1andnotum(a Wnt inhibitor) are expressed in any wound, but 48 hours later they become restricted to posterior or anterior facing wounds, forming the anterior and the posterior organizers, respectively. In this study we undertook a genomic approach to further understand the mechanism that triggers the early expression ofwnt1and the specification of the posterior identity. Through ATAC-sequencing and CHIPmentation techniques we uncovered Cis-Regulatory Elements ofSchmidtea mediterraneagenome and analyzed them innotumandwnt1(RNAi) animals. The result shows that already at 12 hours after amputation the chromatin structure of the wounds has changed its conformation according to the polarity of the pre-existing tissue. Analysing the DNA binding motives present in the proximal regulatory regions of genes down-regulated afterwnt1(RNAi) we found a few genes containing a TCF binding site, which include posterior Homeobox genes and chromatin remodelling proteins, suggesting that those are direct targets of the cWNT pathway and the responsible to trigger the expression of the posterior effectors. Furthermore, we have identified FoxG as an up-stream regulator ofwnt1transcription, probably though binding to an enhancer found in its first intron. Silencing offoxGinhibits the early phase ofwnt1expression and phenocopies thewnt1(RNAi) phenotype, indicating its early role in specifying posteriorversusanterior identity. Moreover, we have created a new open platform to interpret all transcriptomic and genomic results obtained (https://compgen.bio.ub.edu/PlanNET/planexp).
Pathway to Validate Gene Function in Key Bioenergy Crop,Sorghum bicolor
Authors: Aregawi K , Shen J , Pierroz G , Bucheli C , Sharma M , Dahlberg J , Owiti J , Lemaux PG
Published: December 2020

Determining gene function is an essential goal for the key bioenergy crop,Sorghum bicolor(L.) Moench - particularly for genes associated with its notable abiotic stress tolerances. However, detailed molecular understanding of the genes associated with those traits is limited. This was made clear in our in-depth transcriptome studies in sorghum, which indicated nearly 50% of its transcriptome is not annotated. In this report, we describe a full spectrum of tools needed to transform sorghum in order to validate and annotate genes. Efforts began with modifying a transformation method that uses the morphogenic genesBaby BoomandWuschel2(Ovule Development Protein2) to accelerate transformation speed and expand amenable genotypes. In our experience, transforming RTx430 without morphogenic genes requires ~18 to 21 weeks, compared with ~10 to 12 weeks to generate T0plants using methods with morphogenic genes. Utilizing morphogenic genes also allowed for the transformation of several sorghum genotypes not previously transformed or historically recalcitrant to transformation, i.e., rapid cycling SC187, stay-green BTx642, BTx623 and sweet sorghum Ramada. In order to validate candidate genes via engineering, while simultaneously introducing the morphogenic genes, a co-transformation strategy, termed altruistic transformation, was developed. To accomplish editing of the target gene, phytoene desaturase, novel constructs were created that also included morphogenic genes. To enable full characterization of transformed plants, we adapted techniques to determine copy number and independence of events at high-throughput levels. Through these efforts, we created a complete pathway from Agrobacterium infection to high-throughput molecular genotyping that can be used to ascertain gene function and expedite basic genetic research in this widely-grown bioenergy crop plant.
Microglia orchestrate neuronal activity in brain organoids
Authors: Fagerlund Ilkka , Dougalis Antonios , Shakirzyanova Anastasia , Gómez-Budia Mireia , Konttinen Henna , Ohtonen Sohvi , Feroze Fazaludeen , Koskuvi Marja , Kuusisto Johanna , Hernández Damián , Pebay Alice , Koistinaho Jari , Lehtonen Sarka , Korhonen Paula , Malm Tarja
Published: December 2020

Human stem cell-derived brain organoids provide a physiologically relevantin vitro3D brain model for studies of neurological development that are unique to the human nervous system. Prior studies have reported protocols that support the maturation of microglia from mesodermal progenitors leading to innately developing microglia within the organoids. However, although microglia are known to support neuronal development in rodents, none of the previous studies have reported what is the impact of microglia on neuronal growth and maturation in human brain organoids. Here we show that incorporating microglial progenitors into the developing organoid supports neuronal maturation, the emergence of neurons capable of firing repetitive action potentials and the appearance of synaptic and neuronal bursting activity. Immunocompetent organoids enable experimental strategies for interrogating fundamental questions on microglial and neuronal diversity and function during human brain development.
Bioluminescence and fluorescence of three sea pens in the north-west Mediterranean sea
Authors: Francis Warren R , de Vilar Anaïs Sire
Published: December 2020

Bioluminescence of Mediterranean sea pens has been known for a long time, but basic parameters such as the emission spectra are unknown. Here we examined bioluminescence in three species of Pennatulacea,Pennatula rubra, Pteroeides griseum, andVeretillum cynomorium. Following dark adaptation, all three species could easily be stimulated to produce green light. All species were also fluorescent, with bioluminescence being produced at the same sites as the fluorescence. The shape of the fluorescence spectra indicates the presence of a GFP closely associated with light production, as seen inRenilla. Our videos show that light proceeds as waves along the colony from the point of stimulation for all three species, as observed in many other octocorals. Features of their bioluminescence are strongly suggestive of a “burglar alarm” function.
Mysterious disappearances of a large mammal in Neotropical forests
Authors: Fragoso J.M.V. , Antunes A.P. , Altrichter M. , Constantino P.A.L. , Zapata-Ríos G. , Camino M. , de Thoisy B. , Wallace R.B. , El Bizri H.R. , Morcatty T.Q. , Mayor P. , Richard-Hansen C. , Hallett M.T. , Reyna-Hurtado R.A. , Beck H. , de Bustos S. , Bodmer R.E. , Keuroghlian A. , Nava A. , Montenegro O.L. , Painkow Neto E. , Desbiez A.L.J. , Silvius K.M.
Published: December 2020

The drivers of periodic population cycling by some animal species in northern systems remain unresolved1. Mysterious disappearances of populations of the Neotropical, herdforming white-lipped peccary (Tayassu pecari, henceforth “WLP”) have been anecdotally documented and explained as local events resulting from migratory movements or overhunting2,3,4, or as disease outbreaks5,6, and have not been considered in the context of large-scale species-specific population dynamics. Here we present evidence that WLP disappearances represent troughs in population cycles that occur with regular periodicity and are synchronized at regional and perhaps continent-wide spatial scales. Analysis of 43 disappearance events and 88 years of commercial and subsistence harvesting data reveals boom – bust population cycles lasting from 20 to 30 years, in which a rapid population crash occurring over 1 to 5 years is followed by a period of absence of 7 to12 years and then a slow growth phase. Overhunting alone cannot explain the crashes, but as in northern systems dispersal during the growth phase appears to play a key role. This is the first documentation of population cycling in a tropical vertebrate.
Intranasal administration of SARS-CoV-2 neutralizing human antibody prevents infection in mice
Authors: Zhang Hongbing , Yang Zhiyuan , Xiang Jingyi , Cui Ziyou , Liu Jianying , Liu Cheng
Published: December 2020

Prevention of SARS-CoV-2 infection at the point of nasal entry is a novel strategy that has the potential to help contain the ongoing pandemic. Using our proprietary technologies, we have engineered a human antibody that recognizes SARS-CoV-2 S1 spike protein with an enhanced affinity for mucin to improve the antibody’s retention in respiratory mucosa. The modified antibody, when administered into mouse nostrils, was shown to block infection in mice that were exposed to high titer SARS-CoV-2 pseudovirus 10 hours after the initial antibody treatment. Our data show that the protection against SARS-CoV-2 infection is effective in both nasal and lung areas 7 days after viral exposure. The modified antibody is stable in a nasal spray formulation and maintains its SARS-CoV-2 neutralizing activity. Nasal spray of the modified antibody can be developed as an affordable and effective prophylactic product to protect people from infection by exposure to SARS-CoV-2 virus in the air.

One-sentence summary

A Fc-modified human antibody prevents SARS-CoV-2 viral infection via nasal administration
Mechanisms for Communicating in a Marmoset ‘Cocktail Party’
Authors: Jovanovic Vladimir , Miller Cory T
Published: December 2020

A fundamental challenge for audition is parsing the voice of a single speaker amid a cacophony of other voices known as the Cocktail Party Problem (CPP). Despite its prevalence, relatively little remains known about how our simian cousins solve the CPP for active, natural communication. Here we employed an innovative, multi-speaker paradigm comprising five computer-generated Virtual Monkeys (VM) whose respective vocal behavior could be systematically varied to construct marmoset cocktail parties and tested the impact of specific acoustic scene manipulations on vocal behavior. Results indicate that marmosets not only employ auditory mechanisms – including attention – for speaker stream segregation, but also selectively change their own vocal behavior in response to the dynamics of the acoustic scene to overcome the challenges of the CPP. These findings suggest notable parallels between human and nonhuman primate audition and highlight the active role that speakers play to optimize communicative efficacy in complex real-world acoustic scenes.
Making the Most of Potential: Potential Games and Genotypic Convergence
Authors: Edhan OMER , Hellman ZIV , Nehama ILAN
Published: December 2020

Abstract

We consider genotypic convergence of populations and show that under fixed fitness asexual and haploid sexual populations attain monomorphic convergence (even under genetic linkage between loci) to basins of attraction with locally exponential convergence rates; the same convergence obtains in single locus diploid sexual reproduction but to polymorphic populations. Furthermore, we show that there is a unified underlying theory underlying these convergences: all of them can be interpreted as instantiations of players in a potential game implementing a multiplicative weights updating algorithm to converge to equilibrium, making use of the Baum–Eagon Theorem. To analyse varying environments, we introduce the concept of ‘virtual convergence’, under which, even if fixation is not attained, the population nevertheless achieves the fitness growth rate it would have had under convergence to an optimal genotype. Virtual convergence is attained by asexual, haploid sexual, and multi-locus diploid reproducing populations, even if environments vary arbitrarily. We also study conditions for true monomorphic convergence in asexually reproducing populations in varying environments.