bluuebunny/crossref_metadata_2025 huggingface dataset:
Seasonal resource pulses and the foraging depth of a Southern Ocean top predator
Authors: Beltran Roxanne S. , Kilpatrick A. Marm , Breed Greg A. , Adachi Taiki , Takahashi Akinori , Naito Yasuhiko , Robinson Patrick W. , Smith Walker O. , Kirkham Amy L. , Burns Jennifer M.
Published: March 2021

Seasonal resource pulses can have enormous impacts on species interactions. In marine ecosystems, air-breathing predators often drive their prey to deeper waters. However, it is unclear how ephemeral resource pulses such as near-surface phytoplankton blooms alter the vertical trade-off between predation avoidance and resource availability in consumers, and how these changes cascade to the diving behaviour of top predators. We integrated data on Weddell seal diving behaviour, diet stable isotopes, feeding success and mass gain to examine shifts in vertical foraging throughout ice break-out and the resulting phytoplankton bloom each year. We also tested hypotheses about the likely location of phytoplankton bloom origination (advected or producedin situwhere seals foraged) based on sea ice break-out phenology and advection rates from several locations within 150 km of the seal colony. In early summer, seals foraged at deeper depths resulting in lower feeding rates and mass gain. As sea ice extent decreased throughout the summer, seals foraged at shallower depths and benefited from more efficient energy intake. Changes in diving depth were not due to seasonal shifts in seal diets or horizontal space use and instead may reflect a change in the vertical distribution of prey. Correspondence between the timing of seal shallowing and the resource pulse was variable from year to year and could not be readily explained by our existing understanding of the ocean and ice dynamics. Phytoplankton advection occurred faster than ice break-out, and seal dive shallowing occurred substantially earlier than local break-out. While there remains much to be learned about the marine ecosystem, it appears that an increase in prey abundance and accessibility via shallower distributions during the resource pulse could synchronize life-history phenology across trophic levels in this high-latitude ecosystem.
Tactic-specific antimicrobial activity suggests a parental care function for accessory glands in a marine toadfish
Authors: Pepler Meghan A. , Hindra  , Miller Jessica S. , Elliot Marie A. , Balshine Sigal
Published: March 2021

Males of some species possess extra reproductive organs called accessory glands which are outgrowths of the testes or sperm duct. These organs have a well-established role in reproduction; however, they also appear to have other important functions that are less understood. Here, we investigate the function of the highly complex accessory glands of a marine toadfish,
Porichthys notatus
, a fish with two reproductive male types: large care-providing ‘guarder’ males and small non-caring ‘sneaker’ males. While both male types have accessory glands, guarder male accessory glands are much larger relative to their body size. We show that accessory gland fluids strongly inhibit the growth of bacterial genera associated with unhealthy eggs and have no effect on the growth of strains isolated from healthy eggs. This antibacterial effect was particularly pronounced for extracts from guarder males. Furthermore, we demonstrate that both healthy and unhealthy plainfin midshipman eggs have diverse but distinct microbial communities that differ in their composition and abundance. The highly specific inhibitory capacity of accessory gland fluid on bacteria from unhealthy eggs was robust across a wide range of ecologically relevant temperatures and salinities. Collectively, these ecological and molecular observations suggest a care function for the accessory gland mediated by antimicrobial agents.
Series elasticity facilitates safe plantar flexor muscle–tendon shock absorption during perturbed human hopping
Authors: Dick Taylor J. M. , Clemente Christofer J. , Punith Laksh K. , Sawicki Gregory S.
Published: March 2021

In our everyday lives, we negotiate complex and unpredictable environments. Yet, much of our knowledge regarding locomotion has come from studies conducted under steady-state conditions. We have previously shown that humans rely on the ankle joint to absorb energy and recover from perturbations; however, the muscle–tendon unit (MTU) behaviour and motor control strategies that accompany these joint-level responses are not yet understood. In this study, we determined how neuromuscular control and plantar flexor MTU dynamics are modulated to maintain stability during unexpected vertical perturbations. Participants performed steady-state hopping and, at an unknown time, we elicited an unexpected perturbation via rapid removal of a platform. In addition to kinematics and kinetics, we measured gastrocnemius and soleus muscle activations using electromyography andin vivofascicle dynamics using B-mode ultrasound. Here, we show that an unexpected drop in ground height introduces an automatic phase shift in the timing of plantar flexor muscle activity relative to MTU length changes. This altered timing initiates a cascade of responses including increased MTU and fascicle length changes and increased muscle forces which, when taken together, enables the plantar flexors to effectively dissipate energy. Our results also show another mechanism, whereby increased co-activation of the plantar- and dorsiflexors enables shortening of the plantar flexor fascicles prior to ground contact. This co-activation improves the capacity of the plantar flexors to rapidly absorb energy upon ground contact, and may also aid in the avoidance of potentially damaging muscle strains. Our study provides novel insight into how humans alter their neural control to modulatein vivomuscle–tendon interaction dynamics in response to unexpected perturbations. These data provide essential insight to help guide design of lower-limb assistive devices that can perform within varied and unpredictable environments.
Loss of vocal culture and fitness costs in a critically endangered songbird
Authors: Crates Ross , Langmore Naomi , Ranjard Louis , Stojanovic Dejan , Rayner Laura , Ingwersen Dean , Heinsohn Robert
Published: March 2021

Cultures in humans and other species are maintained through interactions among conspecifics. Declines in population density could be exacerbated by culture loss, thereby linking culture to conservation. We combined historical recordings, citizen science and breeding data to assess the impact of severe population decline on song culture, song complexity and individual fitness in critically endangered regent honeyeaters (
Anthochaera phrygia
). Song production in the remaining wild males varied dramatically, with 27% singing songs that differed from the regional cultural norm. Twelve per cent of males, occurring in areas of particularly low population density, completely failed to sing any species-specific songs and instead sang other species' songs. Atypical song production was associated with reduced individual fitness, as males singing atypical songs were less likely to pair or nest than males that sang the regional cultural norm. Songs of captive-bred birds differed from those of all wild birds. The complexity of regent honeyeater songs has also declined over recent decades. We therefore provide rare evidence that a severe decline in population density is associated with the loss of vocal culture in a wild animal, with concomitant fitness costs for remaining individuals. The loss of culture may be a precursor to extinction in declining populations that learn selected behaviours from conspecifics, and therefore provides a useful conservation indicator.
Spirosoma utsteinense sp. nov. isolated from Antarctic ice-free soils from the Utsteinen region, East Antarctica
Authors: Tahon Guillaume , Lebbe Liesbeth , Willems Anne
Published: March 2021

Between 2014 and 2016, 16 Gram-stain-negative, aerobic, rod-shaped and yellow-orange pigmented bacteria were isolated from exposed soils from the Utsteinen region, Sør Rondane Mountains, East Antarctica. Analysis of their 16S rRNA gene sequences revealed that the strains form a separate cluster in the genus

Spirosoma

, with

Spirosoma rigui

KCTC 12531T as its closest neighbour (97.8 % sequence similarity). Comparative genome analysis of two representative strains (i.e. R-68523T and R-68079) of the new group with the type strains of

Spirosoma rigui

(its closest neighbour) and

Spirosoma linguale

(type species of the genus), yielded average nucleotide identity values of 73.9–78.7 %. Digital DNA–DNA reassociation values of the two strains and these type strains ranged from 20.3 to 22.0 %. The predominant cellular fatty acids of the two novel strains were summed feature 3 (i.e. C16 : 1
 ω7c and/or iso-C15 2-OH), C16 : 1
 ω5c, C16 : 0 and iso-C15 : 0. The new

Spirosoma

strains grew with 0–0.5 % (w/v) NaCl, at pH 6.5–8.0 and displayed optimum growth between 15 and 25 °C. Based on the results of phenotypic, genomic, phylogenetic and chemotaxonomic analyses, the new strains represent a novel species of the genus

Spirosoma

for which the name Spirosoma utsteinense sp. nov. is proposed. The type strain is R-68523T (=LMG 31447T=CECT 9925T).
Identification of novel interactions between host and non-structural protein 2C of foot-and-mouth disease virus
Authors: Mahajan Sonalika , Sharma Gaurav Kumar , Bora Kavita , Pattnaik Bramhadev
Published: March 2021

The 2C protein of foot-and-mouth disease virus (FMDV) is reported to play a critical role in the virus replication complex and modulating the host’s immune response. However, the underlying molecular intricacies of subversion of cellular machinery remains poorly understood, thus emphasizing the need to study 2C-host interactions. In this study, we identified the host proteins interacting with the 2C using yeast-two hybrid (Y2H) approach, which is one of the most recognized, high-throughput tools to study protein-protein interactions. The FMDV-2C bait was characterized for auto-activation, toxicity, and expression and was found to be suitable for mating with cDNA library. On preliminary screening a total of 32 interacting host proteins were identified which were reduced to 22 on subsequent confirmation with alternative yeast based assays. Amongst these, NMI/2C interaction has been reported earlier by Wang et al. (2012) and remaining 21 are novel interactions. The Reactome analysis has revealed the role of the identified host proteins in cellular pathways exploited by 2C during FMDV replication. We also confirmed interaction of MARCH7, an E3 ubiquitin ligase with 2C using mammalian two-hybrid system and co-immunoprecipitation. This study leads to the identification of novel 2C interacting host proteins which enhance our understanding of 2C-host interface and may provide checkpoints for development of potential therapeutics against FMDV.
In vivoevaluation of the virucidal efficacy of Chlorhexidine and Povidone-iodine mouthwashes against salivary SARS-CoV-2
Authors: Elzein Rola , Abdel-Sater Fadi , Fakhreddine Soha , Hanna Pierre Abi , Feghali Rita , Hamad Hassan , Ayoub Fouad
Published: March 2021

Background

The oral cavity is potentially high-risk transmitter of COVID-19. Antimicrobial mouthrinses are used in many clinical pre procedural situations for prophylactic purposes. An evident-based investigation for an effective mouthwash solution against salivary SARS-CoV-2 is urgently required for the exposure reduction during dental procedures.

Aims

This study aimed to evaluate in vivo virucidal efficacy of 2 mouthwashes: 1% Povidoneiodine and 0.2% Chlorhexidine as a dental preprocedural oral disinfection against salivary SARS-CoV-2.

Materials and Methods

In this randomized-controlled clinical trial, studied group comprised laboratory-confirmed COVID-19 positive patients through nasopharyngeal swabs. Participants were divided into 3 groups. For 30 seconds, group A gargled with 1% Povidone-iodine, group B mouthrinsed with 0.2% Chlorhexidine and control group C mouthrinsed with distilled water. Saliva samples were collected before and 5 minutes after mouthwash. SARS-CoV-2 rRT-PCR was then performed for each sample. Evaluation of the efficacy was based on difference in Ct value. The analysis of data was carried out usingGraphPad Prismversion 5 for Windows. Paired t test and unpaired t test were used. A probability value of less than 0.05 was regarded as statistically significant.

Results

Sixty-one compliant participants (36 female and 25 male) with a mean age 45.3 ± 16.7 years-old were enrolled. A significant mean Ct value difference (p< 0.0001) between the paired samples in group A (n = 25) and also in group B (n = 27) (p< 0.0001) was found. In contrast, no significant difference (p= 0.566) existed before and after the experiment in the control group C (n = 9). Moreover, a significant difference was noted between the delta Ct of distilled water wash and each of the 2 solutions 1 % Povidone-iodine (p= 0.012) and Chlorhexidine 0.2% (p= 0.0024). No significant difference was found between the delta Ct of patients using 1% Povidone-iodine and Chlorhexidine 0.2% solutions (p= 0.24).

Conclusion

Chlorhexidine 0.2% and 1% Povidone-iodine oral solutions are effective preprocedural mouthwashes against salivary SARS-COV-2 in dental treatments. Their use as a preventive strategy to reduce the spread of COVID-19 during dental practice should be systematically implemented.
KidneyNetwork: Using kidney-derived gene expression data to predict and prioritize novel genes involved in kidney disease
Authors: Boulogne Floranne , Claus Laura R. , Wiersma Henry , Oelen Roy , Schukking Floor , de Klein Niek , Li Shuang , Westra Harm-Jan , van der Zwaag Bert , van Reekum Franka , Sierks Dana , Schönauer Ria , Halbritter Jan , Knoers Nine V.A.M. ,   Genomics England Research Consortium, Deelen Patrick , Franke Lude , van Eerde Albertien M.
Published: March 2021

Background

Genetic testing in patients with suspected hereditary kidney disease may not reveal the genetic cause for the disorder as potentially pathogenic variants can reside in genes that are not yet known to be involved in kidney disease. To help identify these genes, we have developed KidneyNetwork, that utilizes tissue-specific expression to predict kidney-specific gene functions.

Methods

KidneyNetwork is a co-expression network built upon a combination of 878 kidney RNA-sequencing samples and a multi-tissue dataset of 31,499 samples. It uses expression patterns to predict which genes have a kidney-related function and which (disease) phenotypes might result from variants in these genes. We applied KidneyNetwork to prioritize rare variants in exome sequencing data from 13 kidney disease patients without a genetic diagnosis.

Results

KidneyNetwork can accurately predict kidney-specific gene functions and (kidney disease) phenotypes for disease-associated genes. Applying it to exome sequencing data of kidney disease patients allowed us to identify a promising candidate gene for kidney and liver cysts: ALG6.

Conclusion

We present KidneyNetwork, a kidney-specific co-expression network that accurately predicts which genes have kidney-specific functions and can result in kidney disease. We show the added value of KidneyNetwork by applying it to kidney disease patients without a molecular diagnosis and consequently, we propose ALG6 as candidate gene in one of these patients. KidneyNetwork can be applied to clinically unsolved kidney disease cases, but it can also be used by researchers to gain insight into individual genes in order to better understand kidney physiology and pathophysiology.

Significance statement

Genetic testing in patients with suspected hereditary kidney disease may not reveal the genetic cause for the patient’s disorder. Potentially pathogenic variants can reside in genes not yet known to be involved in kidney disease, making it difficult to interpret the relevance of these variants. This reveals a clear need for methods to predict the phenotypic consequences of genetic variation in an unbiased manner. Here we describe KidneyNetwork, a tool that utilizes tissue-specific expression to predict kidney-specific gene functions. Applying KidneyNetwork to a group of undiagnosed cases identified ALG6 as a candidate gene in cystic kidney and liver disease. In summary, KidneyNetwork can aid the interpretation of genetic variants and can therefore be of value in translational nephrogenetics and help improve the diagnostic yield in kidney disease patients.
PD-1highCXCR5–CD4+ Peripheral Helper T (Tph) cells Promote Tissue-Homing Plasmablasts in COVID-19
Authors: Asashima Hiromitsu , Mohanty Subhasis , Comi Michela , Ruff William E. , Hoehn Kenneth B. , Wong Patrick , Cohen Inessa , Coffey Sarah , Raddassi Khadir , Chaudhary Omkar , Unterman Avraham , Emu Brinda , Kleinstein Steven H. , Montgomery Ruth R. , Iwasaki Akiko , Cruz Charles S. Dela , Kaminski Naftali , Shaw Albert C. , Hafler David A. , Sumida Tomokazu S.
Published: March 2021

A dysregulated immune response against coronavirus-2 (SARS-CoV-2) plays a critical role in the outcome of patients with coronavirus disease 2019 (COVID-19). A significant increase in circulating plasmablasts is characteristic of COVID-19 though the underlying mechanisms and its prognostic implications are not known. Here, we demonstrate that in the acute phase of COVID-19, activated PD-1highCXCR5−CD4+ T cells, peripheral helper T cells, (Tph) are significantly increased and promote inflammatory tissue-homing plasmablasts in patients with stable but not severe COVID-19. Analysis of scRNA-seq data revealed that plasmablasts in stable patients express higher levels of tissue-homing receptors including CXCR3. The increased Tph cells exhibited “B cell help” signatures similar to that of circulating T follicular helper (cTfh) cells and promoted B cell differentiation in vitro. Compared with cTfh cells, Tph cells produced more IFNγ, inducing tissue-homing chemokine receptors on plasmablasts. Finally, expansion of activated Tph cells was correlated with the frequency of CXCR3+ plasmablasts in the acute phase of patients with stable disease. Our results demonstrate a novel role for Tph cells in acute viral immunity by inducing ectopic, antibody secreting plasmablasts.
The potential for bike riding across entire cities: quantifying spatial variation in interest in bike riding
Authors: Pearson Lauren K , Dipnall Joanna , Gabbe Belinda , Braaf Sandy , White Shelley , Backhouse Melissa , Beck Ben
Published: March 2021

Background

Riding a bike is beneficial for health, the environment and for reducing traffic congestion. Despite this, bike riding participation in the state of Victoria, Australia, is low. To inform planning and practice, there is a need to understand the proportion of the population (the ‘near-market’) that are interested in riding a bike, and how this varies across regions. The Geller typology classifies individuals into one of four groups, based on their confidence to ride a bike in various infrastructure types, and frequency of bike riding. The typology has been used at a city, state and country-wide scale, however not at a smaller spatial scale. We aimed to characterise and quantify the distribution of the Geller typology within Local Government Areas (LGAs) in the state of Victoria, Australia.

Methods

An online survey was conducted in 37 LGAs in Victoria, including all LGAs in Greater Melbourne, and a selection of six key regional centres. Participants were recruited from an opt-in online research company panel with the objective of recruiting a representative sample of adults across each LGA. The Geller typology classified individuals as either: ‘Strong and Fearless, ‘Enthused and Confident’, ‘Interested but Concerned’, or ‘No Way No How’. ‘Interested but Concerned’ participants are those that would ride a bike if protected infrastructure were provided.

Results

The survey was completed by 3999 individuals. Most participants owned a bike (58%), however only 20% rode at least once per week. The distribution of the Geller groups was: ‘Strong and Fearless’ (3%), ‘Enthused and Confident’ (3%), ‘Interested but Concerned’ (78%), and ‘No Way No How’ (16%). While variation in the distributions of the Geller groups was observed between LGAs within Greater Melbourne., the ‘Interested but Concerned’ group, reflecting people who are comfortable riding only in protected lanes or off-road paths, was high across all LGAs and all demographic sub-groups. Even though the frequency of riding a bike was lower in women, interest in riding a bike was high and comparable to men. Participants who resided in the outer urban fringe regions of Greater Melbourne had high interest, but low participation in bike riding.

Conclusions

While there was variation in interest in bike riding across an entire metropolitan region and across population groups, interest was high across all areas and demographics. Our results show the potential for substantial increases in cycling participation, but only when high-quality cycling infrastructure is provided. Further research is required to understand the policy and practice barriers to equitable provision of protected infrastructure.
Factors associated with the stigma-discrimination complex towards healthcare workers among university students during the coronavirus pandemic in Mexico
Authors: Cassiani-Miranda Carlos Arturo , Álvarez-Solorza Isabel , Campo-Arias Adalberto , Arismendy-López Yinneth Andrea , Tirado-Otálvaro Andrés Felipe , Bustamante-Montes Lilia Patricia , Toxqui-Tlachino María Juana Gloria
Published: March 2021

The COVID-19-related stigma towards healthcare workers negatively influences their performance and job satisfaction, and well-being. The frequency of COVID-19-related stigma towards healthcare workers and its associated factors has not been sufficiently investigated. The objective was to determine the frequency and variables associated with COVID-19-related stigmatisation towards health workers in emerging-age university adults in Mexico. Analytical and cross-sectional study using an online questionnaire in 1,054 students between 18 and 29 years of age. Demographic variables, religiosity, fear of COVID-19 and stigma-discrimination related to COVID-19 towards healthcare workers were analysed. The latter was set as the dependent variable, while demographic variables, religiosity and high fear of COVID-19 were the independent variables. For the association between the variables, a binomial and logarithmic generalised linear model was designed to calculate the adjusted prevalence ratios. The proportion of high stigma-discrimination was 12.4%, and this was associated with a high fear of COVID-19 (APR 1.51, 95% CI 1.06 to 2.23). The main limitations were the cross-sectional nature, social desirability bias, non-probabilistic sampling. The results highlight the importance of establishing programmes to reduce COVID-19-related stigmatisation towards healthcare workers.
Characterizing altruistic motivation in potential volunteers for SARS-CoV-2 challenge trials
Authors: Rose Sophie M , Schmit Virginia L , Darton Thomas C , Eyal Nir , Magalhaes Monica , Morrison Josh , Peeler Matthew , Shah Seema K , Marsh Abigail A
Published: March 2021

In human challenge trials, volunteers are deliberately infected with a pathogen to accelerate vaccine development and answer key scientific questions. In the U.S., preparations for challenge trials with the novel coronavirus are complete, and in the U.K., challenge trials have recently begun. However, ethical concerns have been raised about the potential for invalid consent or exploitation. These concerns largely reflect worries that challenge trial volunteers may be unusually risk-seeking or too economically vulnerable to refuse the payments these trials provide, rather than being motivated primarily by altruistic goals. We conducted the first large-scale survey of intended human challenge trial volunteers and found that SARS-CoV-2 challenge trial volunteers exhibit high levels of altruistic motivations without any special indication of poor risk perception or economic vulnerability. Findings indicate that challenge trials with the novel coronavirus can attract volunteers with background conditions, attitudes, and motivations that should allay key ethical concerns.
A minimal robophysical model of quadriflagellate self-propulsion
Authors: Diaz Kelimar , Robinson Tommie L. , Aydin Yasemin Ozkan , Aydin Enes , Goldman Daniel I. , Wan Kirsty Y.
Published: March 2021

Locomotion at the microscale is remarkably sophisticated. Microorganisms have evolved diverse strategies to move within highly viscous environments, using deformable, propulsion-generating appendages such as cilia and flagella to drive helical or undulatory motion. In single-celled algae, these appendages can be arranged in different ways around an approximately 10µm cell body, and coordinated in distinct temporal patterns. Inspired by the observation that some quadriflagellates (bearing four flagella) have an outwardly similar morphology and flagellar beat pattern, yet swim at different speeds, this study seeks to determine whether variations in swimming performance could arise solely from differences in swimming gait. Robotics approaches are particularly suited to such investigations, where the phase relationships between appendages can be readily manipulated. Here, we developed autonomous, algae-inspired robophysical models that can self-propel in a viscous fluid. These macroscopic robots (length and width = 8.5 cm, height = 2 cm) have four independently actuated ‘flagella’ that oscillate back and forth under low-Reynolds number conditions (Re∼ 𝒪(10−1)). We tested the swimming performance of these robot models with appendages arranged in one of two distinct configurations, and coordinated in one of three distinct gaits. The gaits, namely the pronk, the trot, and the gallop, correspond to gaits adopted by distinct microalgal species. When the appendages are inserted perpendicularly around a central ‘body’, the robot achieved a net performance of 0.15−0.63 body lengths per cycle, with the trot gait being the fastest. Robotic swimming performance was found to be comparable to that of the algal microswimmers across all gaits. By creating a minimal robot that can successfully reproduce cilia-inspired drag-based swimming, our work paves the way for the design of next-generation devices that have the capacity to autonomously navigate aqueous environments.
Deficiency of peroxisomal L-bifunctional protein (EHHADH) causes male-specific kidney hypertrophy and proximal tubular injury in mice
Authors: Ranea-Robles Pablo , Portman Kensey , Bender Aaron , Lee Kyung , He John Cijiang , Mulholland David J , Argmann Carmen , Houten Sander M
Published: March 2021

Background

Proximal tubular (PT) cells are enriched in mitochondria and peroxisomes. Whereas mitochondrial fatty acid oxidation (FAO) plays an important role in kidney function by supporting the high-energy requirements of PT cells, the role of peroxisomal metabolism remains largely unknown. EHHADH, also known as L-bifunctional protein, catalyzes the second and third step of peroxisomal FAO.

Methods

We studied kidneys of WT andEhhadhKO mice using histology, immunohistochemistry, immunofluorescence, immunoblot, RNA-sequencing, metabolomics and orchiectomy.

Results

We observed male-specific kidney hypertrophy and glomerular filtration rate reduction in adultEhhadhKO mice. Transcriptome analysis unveiled a gene expression signature similar to PT injury in acute kidney injury mouse models. This was further illustrated by the presence of KIM-1 (kidney injury molecule-1), SOX-9, and Ki67-positive cells in the PT of maleEhhadhKO kidneys. MaleEhhadhKO kidneys had metabolite changes consistent with peroxisomal dysfunction as well as an elevation in glycosphingolipids levels. Orchiectomy ofEhhadhKO mice reversed kidney enlargement and decreased the number of KIM-1 positive cells. We reveal a pronounced sexual dimorphism in the expression of peroxisomal FAO proteins in mouse kidney, underlining a role of androgens in the kidney phenotype ofEhhadhKO mice.

Conclusions

Our data highlight the importance of EHHADH and peroxisomal metabolism in male kidney physiology and reveal peroxisomal FAO as a sexual dimorphic metabolic pathway in mouse kidneys.
3D genomic capture of regulatory immuno-genetic profiles in COVID-19 patients for prognosis of severe COVID disease outcome
Authors: Hunter Ewan , Koutsothanasi Christina , Wilson Adam , Santos Francisco C. , Salter Matthew , Powell Ryan , Dring Ann , Brajer Paulina , Egan Benedict , Westra Jurjen W. , Ramadass Aroul , Messer William , Brunton Amanda , Lyski Zoe , Vancheeswaran Rama , Barlow Andrew , Pchejetski Dmitri , Robbins Peter A. , Mellor Jane , Akoulitchev Alexandre
Published: March 2021

Human infection with the SARS-CoV-2 virus leads to coronavirus disease (COVID-19). A striking characteristic of COVID-19 infection in humans is the highly variable host response and the diverse clinical outcomes, ranging from clinically asymptomatic to severe immune reactions leading to hospitalization and death. Here we used a 3D genomic approach to analyse blood samples at the time of COVID diagnosis, from a global cohort of 80 COVID-19 patients, with different degrees of clinical disease outcomes. Using 3D whole genomeEpiSwitch®arrays to generate over 1 million data points per patient, we identified a distinct and measurable set of differences in genomic organization at immune-related loci that demonstrated prognostic power at baseline to stratify patients with mild forms of illness and those with severe forms that required hospitalization and intensive care unit (ICU) support. Further analysis revealed both well established and new COVID-related dysregulated pathways and loci, including innate and adaptive immunity; ACE2; olfactory, Gβψ, Ca2+and nitric oxide (NO) signalling; prostaglandin E2 (PGE2), the acute inflammatory cytokine CCL3, and the T-cell derived chemotactic cytokine CCL5. We identified potential therapeutic agents for mitigation of severe disease outcome, with several already being tested independently, including mTOR inhibitors (rapamycin and tacrolimus) and general immunosuppressants (dexamethasone and hydrocortisone). Machine learning algorithms based on establishedEpiSwitch®methodology further identified a subset of 3D genomic changes that could be used as prognostic molecular biomarker leads for the development of a COVID-19 disease severity test.
In Poetry, if Meter has to Help Memory, it Takes its Time
Authors: Andreetta Sara , Soldatkina Oleksandra , Boboeva Vezha , Treves Alessandro
Published: March 2021

To test the idea that poetic meter emerged as a cognitive schema to aid verbal memory, we have focused on classical Italian poetry and on its three basic components of meter: rhyme, accent and verse length. Meaningless poems were generated by introducing prosody-invariant non-words into passages from Dante’sDivina Commediaand Ariosto’sOrlando Furioso, which were then further manipulated by selectively ablating rhymes, modifying accent patterns or altering the number of syllables. The resulting four versions of each non-poem were presented in a fully balanced design to cohorts of high school educated Italian native speakers, who were then asked to retrieve 3 target non-words. Surprisingly, we found that the integrity of Dante’s meter has no significant effect on memory performance. With passages derived from Ariosto, instead, removing each component downgrades memory by an amount proportional to its contribution to perceived metric plausibility, with rhymes having the strongest effects, followed by accents and then by verse length. Counterintuitively, the fully metric versions required longer reaction times, implying that activating metric schemata involves a cognitive cost. Within schema theories, this finding provides evidence for high-level interactions between procedural and episodic memory.
Altered effective connectivity in sensorimotor cortices: a novel signature of severity and clinical course in depression
Authors: Ray Dipanjan , Bezmaternykh Dmitry , Mel’nikov Mikhail , Friston Karl J , Das Moumita
Published: March 2021

Functional neuroimaging research on depression has traditionally targeted neural networks associated with the psychological aspects of depression. In this study, instead, we focus on alterations of sensorimotor function in depression. We used resting-state functional MRI data and Dynamic Causal Modeling (DCM) to assess the hypothesis that depression is associated with aberrant effective connectivity within and between key regions in the sensorimotor hierarchy. Using hierarchical modeling of between-subject effects in DCM with Parametric Empirical Bayes we first established the architecture of effective connectivity in sensorimotor cortices. We found that in (interoceptive and exteroceptive) sensory cortices across participants, the backward connections are predominantly inhibitory whereas the forward connections are mainly excitatory in nature. In motor cortices these parities were reversed. With increasing depression severity, these patterns are depreciated in exteroceptive and motor cortices and augmented in the interoceptive cortex: an observation that speaks to depressive symptomatology. We established the robustness of these results in a leave-one-out cross validation analysis and by reproducing the main results in a follow-up dataset. Interestingly, with (non-pharmacological) treatment, depression associated changes in backward and forward effective connectivity partially reverted to group mean levels. Overall, altered effective connectivity in sensorimotor cortices emerges as a promising and quantifiable candidate marker of depression severity and treatment response.

Significance Statement

Research into neurobiology of depression primarily focuses on its complex psychological aspects. Here, we propose an alternative approach and target sensorimotor alterations - a prominent but often neglected feature of depression. We demonstrated using resting-state fMRI data and computational modelling that top-down and bottom-up information flow in sensory and motor cortices is altered with increasing depression severity in a way that is consistent with depression symptoms. Depression associated changes were found to be consistent across sessions, amenable to treatment and of effect size sufficiently large to predict whether somebody has mild or severe depression. These results pave the way for a new avenue of research into the neural underpinnings of mental health conditions.
Tracing evolution history of 100 whole genome sequences of diffuse stem brain tumor
Authors: Zou Lihua
Published: March 2021

Diffuse intrinsic pontine glioma (DIPG) is a deadly disease among young children. The evolution path and mutational processes giving rise to DIPG remain elusive. We analyzed 100 whole genome sequences (WGS) from 60 DIPG patients. This revealed 25% DIPGs acquired whole-genome duplications (WGD) early during tumor evolution. WGD samples are associated with loss of TP53 and poorer survival. In addition, almost all WGD samplers harbor complex structural variations (SVs) and show characteristic short microhomology at SV breakpoints. Mutation analysis revealed that H3K27M driver mutation is acquired early during tumor clonal evolution. Mutation signature analysis identified a unique mutational process at a late stage of tumor evolution. This study revealed that tumor evolution of DIPG is characterized by chromosomal instability shaped by DNA repair defects and dynamic mutational processes. Our work shed new insights on the disease pathogenesis of DIPG and provided rationale for designing novel therapy for this deadly disease.
Time dependent proinflammatory responses shape virus interference during coinfections of influenza A virus and influenza D virus
Authors: Guan Minhui , Blackmon Sherry , Olivier Alicia K. , Zhang Xiaojian , Liu Liyuan , Woolums Amelia , Crenshaw Mark A. , Liao Shengfa F. , Webby Richard , Epperson William , Wan Xiu-Feng
Published: March 2021

Both influenza A virus (IAV) and influenza D virus (IDV) are enzootic in pigs. IAV causes approximately 100% morbidity with low mortality, whereas IDV leads to only mild respiratory diseases in pigs. In this study, we performed a series of coinfection experimentsin vitroandin vivoto understand how IAV and IDV interact and cause pathogenesis during coinfection. Results showed that IAV inhibited IDV replication when infecting swine tracheal epithelial cells (STEC) with IAV 24- or 48-hours prior to IDV inoculation, and that IDV suppressed IAV replication when IDV preceded IAV inoculation by 48 hours. Virus interference was not identified during simultaneous IAV/IDV infections or with 6 hours between the two viral infections, regardless of their order. The interference pattern at 24- and 48-hours correlated with proinflammatory responses induced by the first infection, which was about 24-hours slower for IDV than IAV. The viruses did not interfere with each other if both infected the cells before proinflammatory responses were induced. Coinfection in pigs further demonstrated that IAV interfered both viral shedding and virus replication of IDV, especially in the upper respiratory tract. Clinically, coinfection of IDV and IAV did not show significant enhancement of disease pathogenesis, compared with the pigs infected with IAV alone. In summary, this study suggests that interference during coinfection of IAV and IDV is primarily due to the proinflammatory response and is therefore dependent on the time between infection, and the order of infection.

Importance

Both IAV and IDV are enzootic in pigs, and feral pigs have a higher risk for both IAV and IDV exposures than IDV exposure alone. This study suggests that in coinfection with IAV and IDV either virus can interfere with the replication of the other virus by stimulating proinflammatory responses; however, the proinflammatory response was 24 hours slower for IDV than IAV.In vitrothere was no interference during simultaneous coinfection, regardless of infection order. Coinfection of IDV and IAV in pigs did not show enhanced pathogenesis, compared with those infected only with IAV. This study can facilitate our understanding of virus epidemiology and pathogenesis associated with IAV and IDV coinfection.
SARS-CoV-2 Epidemiology on a Public University Campus in Washington State
Authors: Weil Ana A. , Sohlberg Sarah L. , O’Hanlon Jessica A. , Casto Amanda M. , Emanuels Anne W , Lo Natalie K. , Greismer Emily P. , Magedson Ariana M. , Wilcox Naomi C. , Kim Ashley E. , Back Lewis , Frazar Christian D. , Pelle Ben , Sibley Thomas R. , Ilcisin Misja , Lee Jover , Ryke Erica L. , Chris Craft J. , Schwabe-Fry Kristen M. , Fay Kairsten A. , Cho Shari , Han Peter D. , Heidl Sarah J. , Pfau Brian A. , Truong Melissa , Zhong Weizhi , Srivatsan Sanjay R. , Harb Katia F. , Gottlieb Geoffrey S. , Hughes James P. , Nickerson Deborah A. , Lockwood Christina M. , Starita Lea M. , Bedford Trevor , Shendure Jay A. , Chu Helen Y.
Published: March 2021

Background

Testing programs have been utilized as part of SARS-CoV-2 mitigation strategies on university campuses, and it is not known which strategies successfully identify cases and contain outbreaks.

Objective

Evaluation of a testing program to control SARS-CoV-2 transmission at a large university.

Design

Prospective longitudinal study using remote contactless enrollment, daily mobile symptom and exposure tracking, and self-swab sample collection. Individuals were tested if the participant was (1) exposed to a known case, developed new symptoms, or reported high-risk behavior, (2) a member of a group experiencing an outbreak, or (3) at baseline upon enrollment.

Setting

An urban, public university during Autumn quarter of 2020

Participants

Students, staff, and faculty.

Measurements

SARS-CoV-2 PCR testing was conducted, and viral genome sequencing was performed.

Results

We enrolled 16,476 individuals, performed 29,783 SARS-CoV-2 tests, and detected 236 infections. Greek community affiliation was the strongest risk factor for testing positive. 75.0% of positive cases reported at least one of the following: symptoms (60.8%), exposure (34.7%), or high-risk behaviors (21.5%). 88.1% of viral genomes (52/59) sequenced from Greek-affiliated students were genetically identical to at least one other genome detected, indicative of rapid SARS-CoV-2 spread within this group, compared to 37.9% (11/29) of genomes from non-Greek students and employees.

Limitations

Observational study.

Conclusion

In a setting of limited resources during a pandemic, we prioritized testing of individuals with symptoms and high-risk exposure during outbreaks. Rapid spread of SARS- CoV-2 occurred within outbreaks without evidence of further spread to the surrounding community. A testing program focused on high-risk populations may be effective as part of a comprehensive university-wide mitigation strategy to control the SARS-CoV-2 pandemic.
Can we predict antibody responses in SARS-CoV-2? A cohort analysis
Authors: Gaeddert Mary , Kitchen Philip , Broger Tobias , Weber Stefan , Bartenschlager Ralf , Plaszczyca Anna , Kräusslich Hans-Georg , Müller Barbara , Souto-Carneiro Margarida , Janssen Maike , Müller-Tidow Carsten , Merle Uta , Herrmann Yannis , Raedeker Lukas , Sebastian Jakob , Brindl Niall , Starck Tim , Denkinger Claudia M.
Published: March 2021

Background

After infection with severe acute respiratory syndrome coronavirus (SARS-CoV-2), Immunoglobulin G (IgG) antibodies and virus-specific neutralizing antibodies (nAbs) develop. This study describes antibody responses in a cohort of recovered COVID-19 patients to identify predictors.

Methods

We recruited patients with confirmed SARS-CoV-2 infection from Heidelberg, Germany. Blood samples were collected three weeks after COVID-19 symptoms ended. Participants with high antibody titers were invited for follow-up visits. IgG titers were measured by the Euroimmun Assay, and nAbs titers in a SARS-CoV-2 infection-based assay.

Results

281 participants were enrolled between April and August 2020 with IgG testing, 145 (51.6%) had nAbs, and 35 (12.5%) had follow-up. The median IgG optical density (OD) ratio was 3.1 (Interquartile range (IQR) 1.6-5.1), and 24.1% (35/145) had a nAb titer>1:80. Higher IgG titers were associated with increased age and more severe disease, and higher nAbs were associated with male gender and CT-value of 25-30 on RT-PCR at diagnosis. The median IgG OD ratio on follow-up was 3.7 (IQR 2.9-5.9), a median increase of 0.5 (IQR −0.3-1.7). Six participants with follow-up nAbs all had titers ≤ 1:80.

Conclusions

While age and disease severity were correlated with IgG responses, predictive factors for nAbs in convalescent patients remain unclear.
Using Machine Learning along with Data Science algorithms to pre-process and forecast COVID-19 Cases and Deaths
Authors: Choudhary Avi
Published: March 2021

The Covid-19 pandemic has taken a major toll on the health and state of our global population. With tough decisions for allocating resources(i.e. vaccines)[1] are being made, forecasting through machine learning has become more important than ever. Moreover, as vaccines are being brought to the public and cases are going down, it is time that we reflect on where the pandemic has taken the most toll:for the purpose of future reform. This research illustrates two different models and algorithms for COVID-19 forecasting: Auto Regressive models and Recurrent Neural Networks(RNNs). The results show the true potential of RNNs to work with sequential and time-series data to forecast future cases and deaths in different states. As the paper utilizes the tanh activation function and multiple LSTM layers, the research will show the importance of machine learning and its ability to help politicians make decisions when it comes to helping states during the pandemic and future reform. The data will also pre-process the time-series data, using rolling statistics and will clean the data for the auto-regressive model and RNN layers. Thus, we show that along with Recurrent Neural Network layers, activation functions also play a crucial role in the accuracy of the forecast.
Acute Respiratory Distress Syndrome is associated with impaired alveolar macrophage efferocytosis
Authors: Mahida Rahul Y. , Scott Aaron , Parekh Dhruv , Lugg Sebastian T. , Hardy Rowan S. , Lavery Gareth G. , Matthay Michael A. , Naidu Babu , Perkins Gavin D. , Thickett David R.
Published: March 2021

Background

Alveolar macrophage dysfunction may contribute to Acute Respiratory Distress Syndrome (ARDS) pathogenesis, however this has been little studied. Objective: To investigate the pathophysiological link between alveolar macrophage efferocytosis, alveolar neutrophil apoptosis and clinical outcomes in ARDS patients, and to determine whether efferocytosis can be restored.

Methods

Ventilated sepsis patients with or without ARDS underwent broncho-alveolar lavage. Apoptosis of alveolar neutrophils was assessed using flow cytometry. Alveolar macrophages were isolated and used in flow cytometric efferocytosis assays with labelled apoptotic neutrophils. Alveolar macrophages were also isolated from the lung tissue of lobectomy patients, then treated with pooled ARDS BAL fluid prior to functional assessment. Rac1 gene expression was assessed using RT-qPCR.

Results

Patients with sepsis-related ARDS have decreased alveolar macrophage efferocytosis and increased alveolar neutrophil apoptosis compared to control ventilated sepsis patients. Across all ventilated sepsis patients, alveolar macrophage efferocytosis correlated negatively with alveolar cytokines (IL-8, IL-1ra), duration of ventilation and mortality. ARDS BAL treatment of alveolar macrophages decreased efferocytosis and Rac1 gene expression, however bacterial phagocytosis was preserved. Unexpectedly, alveolar macrophage efferocytosis receptor expression (MerTK, CD206) decreased and expression of the anti-efferocytosis receptor SIRPα increased following ARDS BAL treatment. Rho-associated kinase inhibition partially restored alveolar macrophage efferocytosis in an in vitro model of ARDS.

Conclusions

Patients with sepsis-related ARDS have impaired AM efferocytosis, which potentially contributes to ARDS pathogenesis and negatively impacts clinical outcomes, including mortality. Strategies to upregulate AM efferocytosis may be of value for attenuating inflammation in ARDS.