bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-reciprocal acoustics in a viscous environment
Authors: Heo Hyeonu , Walker Ezekiel , Zubov Yurii , Shymkiv Dmitrii , Wages Dylan , Krokhin Arkadii , Choi Tae-Youl , Neogi Arup
Published: December 2020

It is demonstrated that acoustic transmission through a phononic crystal with anisotropic solid scatterers becomes non-reciprocal if the background fluid is viscous. In an ideal (inviscid) fluid, the transmission along the direction of broken
P
symmetry is asymmetric. This asymmetry is compatible with reciprocity since time-reversal symmetry (
T
symmetry) holds. Viscous losses break
T
symmetry, adding a non-reciprocal contribution to the transmission coefficient. The non-reciprocal transmission spectra for a phononic crystal of metallic circular cylinders in water are experimentally obtained and analysed. The surfaces of the cylinders were specially processed in order to weakly break
P
symmetry and increase viscous losses through manipulation of surface features. Subsequently, the non-reciprocal part of transmission is separated from its asymmetric reciprocal part in numerically simulated transmission spectra. The level of non-reciprocity is in agreement with the measure of broken
P
symmetry. The reported study contradicts commonly accepted opinion that linear dissipation cannot be a reason leading to non-reciprocity. It also opens a way for engineering passive acoustic diodes exploring the natural viscosity of any fluid as a factor leading to non-reciprocity.
Environmental heterogeneity and population density affect the functional diversity of personality traits in small mammal populations
Authors: Mortelliti Alessio , Brehm Allison M.
Published: December 2020

Understanding factors affecting the functional diversity of ecological communities is an important goal for ecologists and conservationists. Previous work has largely been conducted at the community level; however, recent studies have highlighted the critical importance of considering intraspecific functional diversity (i.e. the functional diversity of phenotypic traits among conspecifics). Further, a major limitation of existing literature on this topic is the lack of empirical studies examining functional diversity ofbehavioural phenotypes—including animal personalities. This is a major shortcoming because personality traits can affect the fitness of individuals, and the composition of personalities in a population can have important ecological consequences. Our study aims to contribute to filling this knowledge gap by investigating factors affecting the functional diversity of personality traits in wild animal populations. Specifically, we predicted that the richness, divergence and evenness associated with personality traits would be impacted by key components of forest structure and would vary between contrasting forest types. To achieve our objective we conducted a fully replicated large-scale field experiment over a 4 year period using small mammal populations as a model system. We found that greater heterogeneity in the cover of shrubs, coarse woody debris and canopy cover was associated with a greater richness, lower divergence and lower evenness in personality traits. Greater population density was associated with greater functional richness and lower functional divergence and evenness of personality traits. To maintain a behaviourally diverse population and its associated functions, managers may promote heterogeneity in vegetation and increased population density, which we found to be the most important determinants driving functional diversity of personality traits.
Flexibility of nutritional strategies within a mutualism: food availability affects algal symbiont productivity in two congeneric sea anemone species
Authors: Bedgood Samuel A. , Mastroni Sarah E. , Bracken Matthew E. S.
Published: December 2020

Mutualistic symbioses are common, especially in nutrient-poor environments where an association between hosts and symbionts can allow the symbiotic partners to persist and collectively out-compete non-symbiotic species. Usually these mutualisms are built on an intimate transfer of energy and nutrients (e.g. carbon and nitrogen) between host and symbiont. However, resource availability is not consistent, and the benefit of the symbiotic association can depend on the availability of resources to mutualists. We manipulated the diets of two temperate sea anemone species in the genusAnthopleurain the field and recorded the responses of sea anemones and algal symbionts in the family Symbiodiniaceae to our treatments. Algal symbiont density, symbiont volume and photosynthetic efficiency of symbionts responded to changes in sea anemone diet, but the responses depended on the species of sea anemone. We suggest that temperate sea anemones and their symbionts can respond to changes in anemone diet, modifying the balance between heterotrophy and autotrophy in the symbiosis. Our data support the hypothesis that symbionts are upregulated or downregulated based on food availability, allowing for a flexible nutritional strategy based on external resources.
Asymmetric interspecific competition drives shifts in signalling traits in fan-throated lizards
Authors: Zambre Amod M. , Khandekar Akshay , Sanap Rajesh , O'Brien Clairissa , Snell-Rood Emilie C. , Thaker Maria
Published: December 2020

Interspecific competition can occur when species are unable to distinguish between conspecific and heterospecific mates or competitors when they occur in sympatry. Selection in response to interspecific competition can lead to shifts in signalling traits—a process called agonistic character displacement. In two fan-throated lizard species—
Sitana laticeps
and
Sarada darwini
—females are morphologically indistinguishable and male agonistic signalling behaviour is similar. Consequently, in areas where these species overlap, males engage in interspecific aggressive interactions. To test whether interspecific male aggression between
Si. laticeps
and
Sa. darwini
results in agonistic character displacement, we quantified species recognition and signalling behaviour using staged encounter assays with both conspecifics and heterospecifics across sympatric and allopatric populations of both species. We found an asymmetric pattern, wherein males of
Si. laticeps
but not
Sa. darwini
showed differences in competitor recognition and agonistic signalling traits (morphology and behaviour) in sympatry compared with allopatry. This asymmetric shift in traits is probably due to differences in competitive abilities between species and can minimize competitive interactions in zones of sympatry. Overall, our results support agonistic character displacement, and highlight the role of asymmetric interspecific competition in driving shifts in social signals.
Two decades of carbonate budget change on shifted coral reef assemblages: are these reefs being locked into low net budget states?
Authors: Molina-Hernández Ana , González-Barrios F. Javier , Perry Chris T. , Álvarez-Filip Lorenzo
Published: December 2020

The ecology of coral reefs is rapidly shifting from historical baselines. One key-question is whether under these new, less favourable ecological conditions, coral reefs will be able to sustain key geo-ecological processes such as the capacity to accumulate carbonate structure. Here, we use data from 34 Caribbean reef sites to examine how the carbonate production, net erosion and net carbonate budgets, as well as the organisms underlying these processes, have changed over the past 15 years in the absence of further severe acute disturbances. We find that despite fundamental benthic ecological changes, these ecologically shifted coral assemblages have exhibited a modest but significant increase in their net carbonate budgets over the past 15 years. However, contrary to expectations this trend was driven by a decrease in erosion pressure, largely resulting from changes in the abundance and size-frequency distribution of parrotfishes, and not by an increase in rates of coral carbonate production. Although in the short term, the carbonate budgets seem to have benefitted marginally from reduced parrotfish erosion, the absence of these key substrate grazers, particularly of larger individuals, is unlikely to be conducive to reef recovery and will thus probably lock these reefs into low budget states.
Electroretinographic study of the magnetic compass in European robins
Authors: Astakhova Luba A. , Rotov Alexander Yu. , Cherbunin Roman V. , Goriachenkov Arsenii A. , Kavokin Kirill V. , Firsov Michael L. , Chernetsov Nikita
Published: December 2020

Migratory birds are known to be sensitive to external magnetic field (MF). Much indirect evidence suggests that the avian magnetic compass is localized in the retina. Previously, we showed that changes in the MF direction could modulate retinal responses in pigeons. In the present study, we performed similar experiments using the traditional model animal to study the magnetic compass, European robins. The photoresponses of isolated retina were recorded usingex vivoelectroretinography (ERG). Blue- and red-light stimuli were applied under an MF with the natural intensity and two MF directions, when the angle between the plane of the retina and the field lines was 0° and 90°, respectively. The results were separately analysed for four quadrants of the retina. A comparison of the amplitudes of the a- and b-waves of the ERG responses to blue stimuli under the two MF directions revealed a small but significant difference in a- but not b-waves, and in only one (nasal) quadrant of the retina. The amplitudes of both the a- and b-waves of the ERG responses to red stimuli did not show significant effects of the MF direction. Thus, changes in the external MF modulate the European robin retinal responses to blue flashes, but not to red flashes. This result is in a good agreement with behavioural data showing the successful orientation of birds in an MF under blue, but not under red illumination.
Pseudomonas cremoris sp. nov., a novel proteolytic species isolated from cream
Authors: Hofmann Katharina , Woller Alexandra , Huptas Christopher , Wenning Mareike , Scherer Siegfried , Doll Etienne V.
Published: December 2020

During a study investigating the microbiota of raw milk and its semi-finished products, strains WS 5106T and WS 5096 were isolated from cream and skimmed milk concentrate. They could be assigned to the genus

Pseudomonas

by their 16S rRNA sequences, but not to any validly named species. In this work, a polyphasic approach was used to characterize the novel strains and to investigate their taxonomic status. Examinations based on the topology of core genome phylogenomy as well as average nucleotide identity (ANIm) comparisons suggested a novel

Pseudomonas

species within the

Pseudomonas fluorescens

subgroup. With pairwise ANIm values of 90.1 and 89.8 %, WS 5106T was most closely related to

Pseudomonas nabeulensis

CECT 9765T and

Pseudomonas kairouanensis

CECT 9766T. The G+C content of strain WS 5106T was 60.1 mol%. Morphologic analyses revealed Gram-stain-negative, aerobic, catalase and oxidase positive, rod-shaped and motile cells. Proteolysis on skimmed milk agar as well as lipolysis on tributyrin agar occurred at both 28 and 6 °C. Tolerated growth conditions were temperatures between 4 and 34 °C, pH values between 6.0 and 8.0, and salt concentrations of up to 5 %. Fatty acid profiles showed a pattern typical for

Pseudomonas

, with C16 : 0 as the dominant component. The major cellular polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol and the dominating quinone was Q-9. Based on these results, it is proposed to classify the strains as a novel species, Pseudomonas cremoris sp. nov., with WS 5106T (=DSM 111143T=LMG 31863T) as type strain and WS 5096 (=DSM 111129=LMG 31864) as an additional strain.
Fundamental differences in physiology of Bordetella pertussis dependent on the two-component system Bvg revealed by gene essentiality studies
Authors: Belcher Thomas , MacArthur Iain , King Jerry D. , Langridge Gemma C. , Mayho Matthew , Parkhill Julian , Preston Andrew
Published: December 2020

The identification of genes essential for a bacterium’s growth reveals much about its basic physiology under different conditions.

Bordetella pertussis

, the causative agent of whooping cough, adopts both virulent and avirulent states through the activity of the two-component system, Bvg. The genes essential for

B. pertussis

growth in vitro were defined using transposon sequencing, for different Bvg-determined growth states. In addition, comparison of the insertion indices of each gene between Bvg phases identified those genes whose mutation exerted a significantly different fitness cost between phases. As expected, many of the genes identified as essential for growth in other bacteria were also essential for

B. pertussis

. However, the essentiality of some genes was dependent on Bvg. In particular, a number of key cell wall biosynthesis genes, including the entire mre/mrd locus, were essential for growth of the avirulent (Bvg minus) phase but not the virulent (Bvg plus) phase. In addition, cell wall biosynthesis was identified as a fundamental process that when disrupted produced greater fitness costs for the Bvg minus phase compared to the Bvg plus phase. Bvg minus phase growth was more susceptible than Bvg plus phase growth to the cell wall-disrupting antibiotic ampicillin, demonstrating the increased susceptibility of the Bvg minus phase to disruption of cell wall synthesis. This Bvg-dependent conditional essentiality was not due to Bvg-regulation of expression of cell wall biosynthesis genes; suggesting that this fundamental process differs between the Bvg phases in

B. pertussis

and is more susceptible to disruption in the Bvg minus phase. The ability of a bacterium to modify its cell wall synthesis is important when considering the action of antibiotics, particularly if developing novel drugs targeting cell wall synthesis.
Head-to-head comparison of SARS-CoV-2 antigen-detecting rapid test with professional-collected nasal versus nasopharyngeal swab
Authors: Lindner Andreas K. , Nikolai Olga , Rohardt Chiara , Burock Susen , Hülso Claudia , Bölke Alisa , Gertler Maximilian , Krüger Lisa J. , Gaeddert Mary , Tobian Frank , Lainati Federica , Seybold Joachim , Jones Terry C. , Hofmann Jörg , Sacks Jilian A. , Mockenhaupt Frank P. , Denkinger Claudia M.
Published: December 2020

Background

Nasopharyngeal (NP) swab samples for antigen-detecting rapid diagnostic tests (Ag-RDTs) require qualified healthcare professionals and are frequently perceived as uncomfortable by patients.

Methods

We performed a manufacturer-independent, prospective diagnostic accuracy study, comparing professional-collected nasal mid-turbinate (NMT) to nasopharyngeal swab, using the test kits of a WHO-listed SARS-CoV-2 Ag-RDT (STANDARD Q COVID-19 Ag Test, SD Biosensor), which is also being distributed by Roche. Individuals with high suspicion for COVID-19 infection were tested. The reference standard was RT-PCR using a combined oro-/nasopharyngeal swab sample. Percent positive and negative agreement, as well as sensitivity and specificity were calculated.

Results

Among the 179 participants, 41 (22.9%) tested positive for SARS-CoV-2 by RT-PCR. The positive percent agreement of the two different sampling techniques for the Ag-RDT was 93.5% (CI 79.3-98.2). The negative percent agreement was 95.9% (CI 91.4-98.1). The Ag-RDT with NMT-sampling showed a sensitivity of 80.5% (33/41 PCR positives detected; CI 66.0-89.8) and specificity of 98.6% (CI 94.9-99.6) compared to RT-PCR. The sensitivity with NP-sampling was 73.2% (30/41 PCR positives detected; CI 58.1-84.3) and specificity was 99.3% (CI 96.0-100). In patients with high viral load (>7.0 log10 SARS-CoV-2 RNA copies/swab), the sensitivity of the Ag-RDT with NMT-sampling was 100% and 94.7% with NP-sampling.

Conclusion

This study demonstrates that sensitivity of a WHO-listed SARS-CoV-2 Ag-RDT using a professional nasal-sampling kit is at least equal to that of the NP-sampling kit, although confidence intervals overlap. Of note, differences in the IFUs of the test procedures could have contributed to different sensitivities. NMT-sampling can be performed with less training, reduces patient discomfort, and it enables scaling of antigen testing strategies. Additional studies of patient self-sampling should be considered to further facilitate the scaling-up of Ag-RDT testing.
A novel homozygous missense mutation p.P388S in TULP1 causes protein instability and retinitis pigmentosa
Authors: Woodard DaNae R. , Xing Chao , Ganne Pratyusha , Liang Hanquan , Mahindrakar Avinash , Sankurathri Chandrasekhar , Hulleman John D. , Mootha V. Vinod
Published: December 2020

Purpose

Retinitis pigmentosa (RP) is an inherited retinal disorder that results in the degeneration of photoreceptor cells, ultimately leading to severe visual impairment. We characterized a consanguineous family from Southern India wherein an individual in his 20’s presented with night blindness since childhood. The purpose of this study was to identify the causative mutation for RP in this individual as well as characterize how the mutation may ultimately affect protein function.

Methods

We performed a complete ophthalmologic examination of the proband followed by exome sequencing. The identified mutation was then modeled in cultured cells, evaluating its expression, solubility (both by western blot), subcellular distribution (confocal microscopy), and testing whether this variant induced endoplasmic reticulum (ER) stress (qPCR and western blotting).

Results

The proband presented with generalized and parafoveal retinal pigment epithelial atrophy with bone spicule pigmentation in the mid periphery and arteriolar attenuation. Optical coherence tomography scans through the macula of both eyes showed atrophy of outer retinal layers with loss of the ellipsoid zone, whereas systemic examination of this individual was normal. The proband’s parents and sibling were asymptomatic and had normal funduscopic examinations. We discovered a novel homozygous p.Pro388Ser mutation in the tubby-like protein 1 (TULP1) gene in the individual with RP. In cultured cells, the P388S mutation does not alter the subcellular distribution of TULP1 or induce ER stress when compared to wild-type TULP1, but instead significantly lowers protein stability as indicated by steady-state and cycloheximide-chase experiments.

Conclusions

These results add to the list of known TULP1 mutations associated with RP and suggest a unique pathogenic mechanism in TULP1-induced RP, which may be shared amongst select mutations in TULP1.
Does HIV impact susceptibility to COVID-19 (SARS-CoV-2) infection and pathology? A review of the current literature
Authors: Aghakishiyeva Elnara , Macallan Derek
Published: December 2020

Objectives

Giving appropriate guidance to people living with HIV (PLWH) during the COVID-19 pandemic depends on having adequate data to inform recommendations. Several studies have now been published which inform such advice. The objective of this study was to collate this information and review the implications of emerging data.

Methods

We performed a systematic literature search of studies relating COVID-19 to HIV infection from the beginning of the pandemic to end of November 2020. We included both published and pre-published manuscripts and analysed papers according to whether they primarily informed risk of infection or risk of adverse outcome.

Results

68 papers (including 11 pre-prints) were identified. In terms of risk of infection, it appears that PLWH are no more or less likely to become infected with COVID-19. In terms of outcomes and mortality, most early small studies did not demonstrate an increase in mortality compared to background populations. However, several larger, more recent studies from South Africa, New York and two from the UK demonstrate higher mortality among PLWH when results are adjusted for other risk factors, giving relative risks of 2.1, 1.2, 1.7 and 2.3 respectively. Apparently conflicting results may arise from differences between studies in their power to account for cofactors and confounding variables. HIV-positive non-survivors tend to be younger and have fewer comorbidities than their HIV-negative counterparts; mortality may be higher in PLWH with low CD4 counts.

Conclusions

Although the literature appears conflicting, large studies which account for covariates strongly suggest that HIV infection increases COVID-19 mortality.
Sensitive detection and quantification of SARS-CoV-2 in saliva
Authors: Abasiyanik Mustafa Fatih , Flood Blake , Lin Jing , Ozcan Sefika , Rouhani Sherin J , Pyzer Athalia , Trujillo Jonathan , Zhen Chaojie , Wu Ping , Jumic Stephen , Wang Andrew , Gajewski Thomas F. , Wang Peng , Hartley Madeline , Ameti Bekim , Niemiec Rachael , Fernando Marian , Aydogan Bulent , Bethel Cindy , Matushek Scott , Beavis Kathleen G. , Agrawal Nishant , Segal Jeremy , Tay Savaş , Izumchenko Evgeny
Published: December 2020

Saliva has significant advantages as a test medium for detection of SARS-CoV-2 infection in patients, such as ease of collection, minimal requirement of supplies and trained personnel, and safety. Comprehensive validation in a large cohort of prospectively collected specimens with unknown SARS-CoV-2 status should be performed to evaluate the potential and limitations of saliva-based testing. We developed a saliva-based testing pipeline for detection of SARS-CoV-2 nucleic acids using real-time reverse transcription PCR (RT-PCR) and droplet digital PCR (ddPCR) readouts, and measured samples from 137 outpatients tested at a curbside testing facility and 29 inpatients hospitalized for COVID-19. These measurements were compared to the nasal swab results for each patient performed by a certified microbiology laboratory. We found that our saliva testing positively detects 100% (RT-PCR) and 93.75% (ddPCR) of curbside patients that were identified as SARS-CoV-2 positive by the Emergency Use Authorization (EUA) certified nasal swab testing assay. Quantification of viral loads by ddPCR revealed an extremely wide range, with 1 million-fold difference between individual patients. Our results demonstrate for both community screening and hospital settings that saliva testing reliability is on par with that of the nasal swabs in detecting infected cases, and has potential for higher sensitivity when combined with ddPCR in detecting low-abundance viral loads that evade traditional testing methods.
At-home self-testing of teachers with a SARS-CoV-2 rapid antigen test to reduce potential transmissions in schools
Authors: Hoehl Sebastian , Schenk Barbara , Rudych Olga , Göttig Stephan , Foppa Ivo , Kohmer Niko , Karaca Onur , Toptan Tuna , Ciesek Sandra
Published: December 2020

Background

Rapid antigen tests for SARS-CoV-2 became available recently, offering an opportunity to vastly increase testing capacities. Antigen tests offer lower sensitivity than the gold standard, RT-PCR, but rapid sample-to-answer time. High-frequency testing with an antigen test may offset the lower sensitivity, and testing can be done with at-home collection of samples, offering potential benefit in screening efforts. In this study, we set out to evaluate the practical application of self-performed high-frequency antigen test in a school setting.

Method

A total of 711 teachers from 86 schools were enrolled in a seven-week study. After instruction, participants tested themselves every 48 hours at home with a rapid antigen test for SARS-CoV-2 (target: nucleocapsid protein) in a self-collected anterior nasal swab. Positive results in the antigen test were confirmed via RT-PCR from the same sample that had been determined to be positive by the study participant. A questionnaire was given to all participants to evaluate whether the test failed to detect infection.

Findings

10 836 tests from 602 teachers were recorded and analyzed. A total of five confirmed cases of viral shedding of SARS-CoV-2 was detected by use of the antigen test. One study participant with a SARS-CoV-2 infection was presymptomatic and four were mildly symptomatic at the time of the antigen test. Sixteen false positive antigen tests (0.15% of all tests) were reported, predominantly when the local incidence in the general population was low. In four cases, the study participant reported that a PCR had detected a SARS-CoV-2 infection, but the antigen test was negative, indicating a false negative result.

Interpretation

High-frequency, self-performed rapid antigen tests can detect individuals with a SARS-CoV-2 infection, and therefore potentially reduce transmissions. Testing may be most beneficial when applied during high local incidence of SARS-CoV-2 infections and when mild or atypical symptoms are present. To avoid a high rate of false positive results, a test with optimized specificity should be used.

Funding

The study was commissioned and funded by the Hessian Ministry of Education and the Hessian Ministry of Integration and Social Affairs.
A Mendelian randomisation study of smoking causality in IPF compared with COPD
Authors: Duckworth Anna , Gibbons Michael A. , Beaumont Robin N , Wood Andrew R , Almond Howard , Lunnon Katie , Lindsay Mark A. , Scotton Chris J , Tyrrell Jess
Published: December 2020

In a normal year, the fatal lung disease Idiopathic Pulmonary Fibrosis (IPF) accounts for ∼1% of UK deaths. Smoking is a recognised risk factor for IPF but the question of causality remains unanswered. Here, we used data from the UK Biobank (UKBB) and the well-established genetic technique of Mendelian randomisation (MR) methods to investigate whether smoking is causal for IPF compared with COPD, where causality is established.

We looked at observational associations in unrelated Europeans, with 871 IPF cases, 11,413 COPD cases and 366,942 controls. We performed analyses using one-sample MR to test for inferred smoking causality in ever smokers using genetic variants that have a previously demonstrated association with smoking heaviness.

Strong associations between disease status and ever having smoked were found in both IPF (OR = 1.52; 95%CI:1.32-1.74; P=2.4×10−8) and COPD (OR= 5.77; 95%CI:5.48-6.07; P<1×10−15). Using MR, a one allele increase in smoking volume genetic risk score was associated with higher odds of COPD in ever smokers, (OR = 4.32; 95%CI:3.37-5.54; P<1×10−15), but no association was seen in IPF (OR=0.55; 95%CI: 0.17-1.81; P=0.33). No association was found between the genetic risk score and disease prevalence in never smokers with IPF (OR = 1.00; 95%CI:0.98-1.02; P=1.00) or COPD (OR = 1.00; 95%CI:0.99-1.01; P=0.53).

Although both IPF and COPD are observationally associated with smoking, our analysis provides evidence inferring that the association is causal in COPD but there is no such evidence in IPF. This suggests that other environmental exposures also need consideration in IPF.
Shift work is associated with positive COVID-19 status in hospitalised patients
Authors: Maidstone Robert , Anderson Simon G , Ray David W , Rutter Martin K , Durrington Hannah J , Blaikley John F
Published: December 2020

Introduction

Shift work is associated with both mental, and physical ill health, including lung disease and infections. However, the impact of shift work on significant COVID-19 illness has not be assessed. We therefore investigated whether shift work is associated with COVID-19.

Methods

501,000 UK biobank participants were linked to secondary care SARS-CoV-2 PCR results from public health England. Healthcare workers and those without an occupational history were excluded from analysis.

Results

Multivariate logistic regression taking into account age, sex, ethnicity and deprivation index revealed that irregular shift work (OR 2.42 95%CI 1.92-3.05), permanent shift work (OR 2.5, 95%CI 1.95-3.19), day shift work (OR 2.01, 95%CI 1.55-2.6), irregular night shift work (OR 3.04, 95%CI 2.37-3.9) and permanent night shift work (OR 2.49, 95%CI 1.67-3.7) were all associated with positive COVID-19 tests compared to participants that did not perform shift work. This relationship persisted after adding sleep duration, chronotype, pre-morbid disease, BMI, alcohol and smoking. Work factors (proximity to a colleague combined with estimated disease exposure) were positively correlated with COVID-19 incidence (r2=0.248, p=0.02). If this was added to the model shift work frequency remained significantly associated with COVID-19. To control for non-measured occupational factors the incidence of COVID-19 in shift workers was compared to colleagues in the same job who did not do shift work. Shift workers had a higher incidence of COVID-19 (p<0.01).

Conclusions

Shift work is associated with a higher likelihood of in-hospital COVID-19 positivity. This risk could potentially be mitigated via additional workplace precautions or vaccination.
The Feasibility of Studying Metabolites in PICU Multi-Organ Dysfunction Syndrome Patients Over an 8-day Course Using An Untargeted Approach
Authors: Leimanis-Laurens Mara L. , Gil Danny , Kampfshulte Andrew , Krohn Claire , Prentice Elizabeth , Sanfilippo Dominic , Prokop Jeremy W. , Lydic Todd , Rajasekaran Surender
Published: December 2020

Metabolites are generated from critical biological functions and metabolism. This pediatric study reviewed plasma metabolites in patients suffering from multi-organ dysfunction syndrome (MODS) in the pediatric intensive care unit (PICU) using an untargeted metabolomics approach. Patients meeting criteria for MODS were screened for eligibility and consented (n=24), and blood samples were collected at baseline, 72 hours, and 8 days; control patients (n=4), were presenting for routine sedation in an outpatient setting. A sub-set of MODS patients (n=8) required additional support with veno-atrial extracorporeal membrane oxygenation (VA-ECMO) therapy. Metabolites from thawed blood plasma were determined from ion pairing reversed-phase LC-MS analysis. Chromatographic peak alignment, identification, relative quantitation, statistical and bioinformatics evaluation were performed using MAVEN and MetaboAnalyst 4.0. Metabolite analysis revealed 115 peaks per sample. From the PLS-DA with VIP scores above ≥2.0, 7 dynamic metabolites emerged over the 3 time points: tauro-chenodeoxycholic acid (TCDCA), hexose,p-hydroxybenzoate, hydroxyphenylacetic acid (HPLA), 2_3-dihydroxybenzoic acid, 2-keto-isovalerate, and deoxyribose phosphate. After Bonferonni adjustment for repeated measures hexose andp-hydroxybenzoate were significant at one time point, or more. Kendall’s tau-b test was used for internal validation of creatinine. Metabolites may be benign or significant in describing a patient’s pathophysiology and require operator interpretation.
COVID-19 RELATED IMMUNIZATION DISRUPTIONS IN RAJASTHAN, INDIA: A RETROSPECTIVE OBSERVATIONAL STUDY
Authors: Jain Radhika , Chopra Ambika , Falézan Camille , Patel Mustufa , Dupas Pascaline
Published: December 2020

Introduction

Governments around the world suspended immunization outreach to control COVID-19 spread. Many have since resumed services with an emphasis on catch-up vaccinations to reach children with missed vaccinations. This paper evaluated immunization disruptions during India’s March-May 2020 lockdown and the extent to which subsequent catch-up efforts reversed them in Rajasthan, India.

Methods

In this retrospective observational study, we conducted phone surveys to collect immunization details for 2,144 children that turned one year old between January and October 2020. We used logistic regressions to compare differences in immunization timeliness and completed first-year immunization status among children that were due immunizations just before (unexposed), during (heavily exposed), and after (post-exposure) the lockdown.

Results

Relative to unexposed children, heavily exposed children were significantly less likely to be immunized at or before 9 months (OR 0.550; 95%CI 0.367-0.824; p=0.004), but more likely to be immunized at 10-12 months (OR 1.761; 95%CI 1.196-2.591; p=0.004). They were also less likely to have completed their key first-year immunizations (OR 0.624; 95%CI 0.478-0.816; p=0.001) by the time of survey. In contrast, post-exposure children showed no difference in timeliness or completed first-year immunizations relative to unexposed children, and their immunization coverage was 6.9pp above heavily exposed children despite their younger age. Declines in immunization coverage were larger among children in households that were poorer, less educated, lower caste, and residing in COVID red zones, although subgroup comparisons were not statistically significant.

Conclusion

Disruptions to immunization services resulted in children missing immunization during the lockdown, but catch-up efforts after it was eased ensured many children were reached at later ages. Nevertheless, catch-up was incomplete and children due their immunizations during the lockdown remained less likely to be fully immunized 4-5 months after it lifted, even as younger cohorts due immunizations in June or later returned to pre-lockdown schedules.
PANOPLY: A cloud-based platform for automated and reproducible proteogenomic data analysis
Authors: Mani D. R. , Maynard Myranda , Kothadia Ramani , Krug Karsten , Christianson Karen E. , Heiman David , Clauser Karl R. , Birger Chet , Getz Gad , Carr Steven A.
Published: December 2020

Proteogenomics involves the integrative analysis of genomic, transcriptomic, proteomic and post-translational modification data produced by next-generation sequencing and mass spectrometry-based proteomics. Several publications by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and others have highlighted the impact of proteogenomics in enabling deeper insight into the biology of cancer and identification of potential drug targets. In order to encapsulate the complex data processing required for proteogenomics, and provide a simple interface to deploy a range of algorithms developed for data analysis, we have developed PANOPLY—a cloud-based platform for automated and reproducible proteogenomic data analysis. A wide array of algorithms have been implemented, and we highlight the application of PANOPLY to the analysis of cancer proteogenomic data.
Cognitive and neural bases of decision-making causing civilian casualties during intergroup conflict
Authors: Han Xiaochun , Zhou Shuai , Fahoum Nardine , Wu Taoyu , Gao Tianyu , Shamay-Tsoory Simone , Gelfand Michele J. , Wu Xinhuai , Han Shihui
Published: December 2020

Civilian casualties occur during military attacks. Such “collateral damage” is prohibited by international laws but increases with substantial consequences when intergroup conflict escalates. Here, we investigate cognitive and neural bases of decision-making processes resulting in civilian harm, using a task that simulates punishment decision-making during intergroup conflict. We test two groups of Chinese participants in a laboratory setting, and two ethnic groups (Jewish and Palestinian) in Israel. The results dissociate two psychological constructs, harm preference and harm avoidance, which respectively characterize punishment decision-making related to outgroup combatants and outgroup noncombatants during intergroup conflict. In particular, individuals show decreased avoidance of harming outgroup noncombatants when conflict escalates. Brain imaging (functional magnetic resonance imaging) reveals that decreased harm avoidance is predicted by inhibition of the left middle frontal activity during selection of punishment decisions. Our findings provide insight into the cognitive and neural bases of decision-making involving civilian harm during intergroup conflict.
Impact of evolutionary selection on dynamic behavior of MCAK protein
Authors: Limbu Shiwani
Published: December 2020

Kinesins of class 13 (kinesin-13s), also known as KinI family proteins, are non-motile microtubule binding kinesin proteins. Mitotic centromere-associated kinesin (MCAK), a member of KinI family protein, diffuses along the microtubule and plays a key role in microtubule depolymerization. Here we have demonstrated the role of evolutionary selection in MCAK protein coding region in regulating its dynamics associated with microtubule binding and stability. Our results indicate that evolutionary selection within MCAK motor domain at amino acid position 440 in carnivora and artiodactyla order results in significant change in the dynamics ofα – helixand loop 11, indicating its likely impact on changing the microtubule binding and depolymerization process. Furthermore, evolutionary selections at amino acid position 600, 617 and 698 are likely to affect MCAK stability. A deeper understanding of evolutionary selections in MCAK can reveal the mechanism associated with change in microtubule dynamics within eutherian mammals.
Handling and accuracy of four rapid antigen tests for the diagnosis of SARS-CoV-2 compared to RT-qPCR
Authors: Olearo Flaminia , Nörz Dominik , Heinrich Fabian , Sutter Jan Peter , Rödel Kevin , Schultze Alexander , Zur Wiesch Julian Schulze , Braun Platon , Oesterreich Lisa , Kreuels Benno , Wichmann Dominic , Aepfelbacher Martin , Pfefferle Susanne , Lütgehetmann Marc
Published: December 2020

Background

SARS-CoV-2 molecular diagnostics is facing material shortages and long turnaround times due to exponential increase of testing demand.

Objective

We evaluated the analytic performance and handling of four rapid Antigen Point of Care Tests (AgPOCTs) I-IV (Distributors: (I) Roche, (II) Abbott, (III) MEDsan and (IV) Siemens).

Methods

100 RT-PCR negative and 84 RT-PCR positive oropharyngeal swabs were prospectively collected and used to determine performance and accuracy of these AgPOCTs. Handling was evaluated by 10 healthcare workers/users through a questionnaire.

Results

The median duration from symptom onset to sampling was 6 days (IQR 2-12 days). The overall relative sensitivity was 49.4%, 44.6%, 45.8% and 54.9 % for tests I, II, III and IV, respectively. In the high viral load subgroup (containing >106copies of SARS-CoV-2 /swab, n=26), AgPOCTs reached sensitivities of 92.3% or more (range 92.3%-100%). Specificity was 100% for tests I, II and IV and 97% for test III. Regarding handling, test I obtained the overall highest scores, while test II was considered to have the most convenient components. Of note, users considered all assays, with the exception of test I, to pose a significant risk for contamination by drips or spills.

Discussion

Besides some differences in sensitivity and handling, all four AgPOCTs showed acceptable performance in high viral load samples. However, due to the significantly lower sensitivity compared to RT-qPCR, a careful consideration of pro and cons of AgPOCT has to be taken into account before clinical implementation.
Source-sink dynamics can maintain mismatched range and bioclimatic limits even at large spatial scales
Authors: Goel Nikunj , Keitt Timothy H.
Published: December 2020

Bioclimatic models assume that at broad spatial scales, climate is the primary determinant of species distribution. Meanwhile, processes such as source-sink dynamics can be ignored because they are thought to manifest at length scales comparable to species mean dispersal distance. We present a reaction-diffusion model to show species can use sink patches near the bioclimatic (or niche) limit as stepping-stones to occupy sinks much further than the mean dispersal distance, thereby extending the distribution far beyond the bioclimatic envelope. This mismatch between geographical and bioclimatic limits is mediated by the shape of the bioclimatic limit and may be significant for low growth sensitivity and fast dispersal life strategy. These findings challenge one of the core assumptions of the bioclimatic models. Therefore, we advocate that biogeographers consider the role of dispersal when using bioclimatic models to generate inferences about the ecological and evolutionary processes that determine the distribution of biota.
DIFFERENTIAL EXPRESSION OF CB1 CANNABINOID RECEPTOR AND CANNABINOID RECEPTOR INTERACTING PROTEIN 1A IN LABOR
Authors: Kozakiewicz Melissa L. , Zhang Jie , Leone-Kabler Sandra , Yamaleyeva Liliya M. , Brost Brian C. , Howlett Allyn C.
Published: December 2020

Background

The endocannabinoid system is present in multiple organ systems and is involved in smooth muscle regulation, immune function, neuroendocrine modulation and metabolism of tissues. Limited data are available regarding the presence and role of this system in reproductive tissues. Components of the endocannabinoid system have been identified in myometrial and placental tissues. However, no study has investigated differential expression of the endocannabinoid system in labor.

Objectives

The purpose of this study was to identify and quantify two components of the endocannabinoid system, the CB1 cannabinoid receptor and cannabinoid receptor interacting protein 1a, in uterine and placental tissues, and to determine if there is differential expression in tissues exposed to labor. We hypothesized that CB1 cannabinoid receptor concentration would be altered in uterine and placental tissue exposed to labor as compared to tissues not exposed to labor.

Study Design

Uterine and placental tissue samples were collected in nine laboring and 11 non-laboring women undergoing cesarean delivery. CB1 cannabinoid receptor and cannabinoid receptor interacting protein 1a presence and quantification were evaluated using western blot and real-time quantitative polymerase chain reaction. Statistical comparisons of laboring and non-laboring subjects were made for uterine and placental tissue using a Mann-Whitney test.

Results

The protein abundance of CB1 cannabinoid receptor in uterine tissue was significantly lower in tissues exposed to labor (p = 0.01). The protein abundance of cannabinoid receptor interacting protein 1a was lower in uterine tissue exposed to labor but did not reach statistical significance (p = 0.06). mRNA expression of CB1 cannabinoid receptor (p = 0.20) and cannabinoid receptor interacting protein 1a (p = 0.63) did not differ in labored compared to non-labored uterine tissues.

Conclusions

Our findings of diminished protein density of CB1 cannabinoid receptor in uterine tissue exposed to labor support the hypothesis that the endocannabinoid system plays a role in parturition. Our data add to the growing body of evidence indicating the endocannabinoid system is of importance for successful reproduction and support the need for additional research investigating this complex system as it pertains to labor.
Tau-mediated axonal degeneration is prevented by activation of the WldSpathway
Authors: Stubbs Katy , Sealey Megan , Moreno Miguel Ramirez , Perry V Hugh , Newman Tracey A , Mudher Amritpal
Published: December 2020

Tauopathy is characterised by neuronal dysfunction and degeneration occurring as a result of changes to the microtubule associated protein tau. The neuronal changes evident in Tauopathy bear striking morphological resemblance to those reported in models of Wallerian degeneration. The mechanisms underpinning Wallerian degeneration are not fully understood although it can be delayed by the expression of the slow Wallerian degeneration (WldS) protein, which has also been demonstrated to delay axonal degeneration in some models of neurodegenerative disease. Given the morphological similarities between tauopathy and Wallerian degeneration, this study investigated whether tau-mediated phenotypes can be modulated by expression of WldS. In aDrosophilamodel of tauopathy in which expression of human Tau protein (hTau0N3R) leads to progressive age-dependent phenotypes, activation of the pathway downstream of WldScompletely suppressed tau-mediated degeneration. This protective effect was evident even if the pathway downstream of WldSwas activated several weeks after hTau-mediated degeneration had become established. In contrast, WldSexpression without activation of the downstream protective pathway did not rescue tau-mediated degeneration in adults or improve tau-mediated neuronal dysfunction including deficits in axonal transport, synaptic alterations and locomotor behaviour in hTau0N3R–expressing larvae. This collectively implies that the pathway mediating the protective effect of WldSintersects with the mechanism(s) of degeneration initiated by hTau and can effectively halt tau-mediated degeneration at both early and late stages. Understanding the mechanisms underpinning this protection could identify much-needed disease-modifying targets for tauopathies.
A slow-exchange conformational switch regulates off-target cleavage by high-fidelity Cas9
Authors: De Paula Viviane S. , Dubey Abhinav , Arthanari Haribabu , Sgourakis Nikolaos G.
Published: December 2020

The Cas9 endonuclease is broadly used for genome engineering applications by programming its single-guide RNA, where high specificity is required. Although mechanistic understanding of DNA cleavage in the CRISPR-Cas9 system has been guided by crystallographic structures and single-molecule FRET experiments, the role of conformational plasticity within its DNA recognition lobe (REC) for target accuracy remains elusive. Through NMR analysis of milliseconds-timescale dynamics, we show that the REC3 domain exchanges between a major, closed and a minor, open conformation. We find that a single mutation in the HiFi Cas9 variant (R691A) increases conformational dynamics in REC3, eliciting a global transition to the open conformation which is regulated by an intramolecular salt-bridge network. These observations suggest a mechanism for reduced off-target recognition by switching on a global conformational exchange process to allow REC3 scanning for proper base pairing. Our data establish a framework for rational engineering Cas9 variants with improved target discrimination.
A new hypothesis for type 1 diabetes risk: The at-risk allele at rs3842753 associates with increased beta cellINSmRNA in a meta-analysis of single cell RNA sequencing data
Authors: Wang Su , Flibotte Stephane , Camunas-Soler Joan , MacDonald Patrick E. , Johnson James D.
Published: December 2020

Type 1 diabetes is characterized by the autoimmune destruction of insulin secreting β cells. Genetic variations upstream at the insulin (INS) locus contribute to ~10% of type 1 diabetes heritable risk. Multiple studies showed an association between rs3842753 C/C genotype and type 1 diabetes susceptibility, but the molecular mechanisms remain unclear. To date, no large-scale studies have looked at the effect of genetic variation at rs3842753 onINSmRNA at the single cell level. We aligned all human islet single cell RNA sequencing datasets available to us in 2020 to the reference genome GRCh38.98 and genotyped rs3842753, integrating 2315 β cells and 1223 β-like cells from 13 A/A protected donors, 23 A/C heterozygous donors, and 35 C/C at-risk donors, including adults without diabetes and with type 2 diabetes.INSexpression mean and variance were significantly higher in single β cells from females compared with males. Comparing across β cells and β-like cells, we found that rs3842753 C containing cells (either homozygous or heterozygous) had the highestINSexpression. We also found that β cells with the rs3842753 C allele had significantly higher ER stress marker gene expression compared to the A/A homozygous genotype. These findings support the emerging concept that inherited risk of type 1 diabetes may be associated with inborn, persistent elevated insulin production which may lead to β cell ER stress and fragility.