bluuebunny/crossref_metadata_2025 huggingface dataset:
Susceptibility of Midge and Mosquito Vectors to SARS-CoV-2
Authors: Balaraman Velmurugan , Drolet Barbara S , Gaudreault Natasha N , Wilson William C , Owens Jeana , Bold Dashzeveg , Swanson Dustin A , Jasperson Dane C , Noronha Leela E , Richt Juergen A , Mitzel Dana N
Published: March 2021

SARS-CoV-2 is a recently emerged, highly contagious virus and the cause of the current COVID-19 pandemic. It is a zoonotic virus, although its animal origin is not clear yet. Person-to-person transmission occurs by inhalation of infected droplets and aerosols, or by direct contact with contaminated fomites. Arthropods transmit numerous viral, parasitic, and bacterial diseases; however, the potential role of arthropods in SARS-CoV-2 transmission is not fully understood. Thus far, a few studies have demonstrated that SARS-CoV-2 replication is not supported in cells from certain insect species nor in certain species of mosquitoes after intrathoracic inoculation. In this study, we expanded the work of SARS-CoV-2 susceptibility to biting insects after ingesting a SARS-CoV-2-infected bloodmeal. Species tested included Culicoides sonorensis (Wirth & Jones) (Diptera: Ceratopogonidae) biting midges, as well as Culex tarsalis (Coquillett) and Culex quinquefasciatus (Say) mosquitoes (Diptera: Culicidae), all known biological vectors for numerous RNA viruses. Arthropods were allowed to feed on SARS-CoV-2-spiked blood and at a time point postinfection analyzed for the presence of viral RNA and infectious virus. Additionally, cell lines derived from C. sonorensis (W8a), Aedes aegypti (Linnaeus) (Diptera: Culicidae) (C6/36), Cx. quinquefasciatus (HSU), and Cx. tarsalis (CxTrR2) were tested for SARS-CoV-2 susceptibility. Our results indicate that none of the biting insects, nor the insect cell lines evaluated support SARS-CoV-2 replication, suggesting that these species are unable to be biological vectors of SARS-CoV-2.
A Tale of Two Meckel’s: small bowel obstruction secondary to Meckel’s Diverticulum
Authors: Ebrahimi Nargus , Quinn Rakesh , Liang Yi , Curran Richard
Published: March 2021

We present two rare cases of small bowel obstruction (SBO) secondary to Meckel’s diverticulum (MD) where the mechanism of obstruction was not readily apparent. Both were cases of virgin abdomen with pre-operative CT scans demonstrating SBO without a clear underlying cause or mass. Diagnostic laparoscopy was performed, which established the underlying cause to be MD, and laparoscopic-assisted resection was undertaken to resect small bowel and perform a side-to-side stapled anastomosis. We subsequently describe the different mechanisms by which MD can cause obstruction as described in the literature.
Risk-Efficient Bayesian Data Synthesis for Privacy Protection
Authors: Hu Jingchen , Savitsky Terrance D , Williams Matthew R
Published: March 2021

Statistical agencies utilize models to synthesize respondent-level data for release to the public for privacy protection. In this study, we efficiently induce privacy protection into any Bayesian synthesis model by employing a pseudo-likelihood that exponentiates each likelihood contribution by an observation record-indexed weight ∈[0,1], defined to be inversely proportional to the identification risk for that record. We start with the marginal probability of identification risk for a record, which is composed as the probability that the identity of the record may be disclosed. Our application to the Consumer Expenditure Surveys (CE) of the U.S. Bureau of Labor Statistics demonstrates that the marginally risk-weighted synthesizer provides an overall improved privacy protection. However, the identification risks actually increase for some moderate-risk records after risk-weighted pseudo-posterior estimation synthesis owing to increased isolation after weighting, a phenomenon we label “whack-a-mole.” We proceed to construct a weight for each record from a collection of pairwise identification risk probabilities with other records, where each pairwise probability measures the joint probability of reidentification of the pair of records, which mitigates the whack-a-mole issue and produces a more efficient set of synthetic data with lower risk and higher utility for the CE data.
Diagnosis of Eating Disorders Among College Students: A Comparison of Military and Civilian Students
Authors: Falvey Sarah E , Hahn Samantha L , Anderson Olivia S , Lipson Sarah K , Sonneville Kendrin R
Published: March 2021

Introduction

Eating disorders are often under-detected, which poses a serious threat to the health of individuals with eating disorder symptoms. There is evidence to suggest that the military represents a subpopulation that may be susceptible to high prevalence of eating disorders and vulnerable to their underdiagnosis. Underreporting of eating disorder symptoms in the military could lead to this underdiagnosis of individuals with eating disorder symptoms. The purpose of this study was to examine the association between military affiliation and eating disorder symptoms among college students and the likelihood of eating disorder diagnosis among those with eating disorder symptoms using a large, diverse college-aged sample of both military-involved and civilian students.

Materials and Methods

Participants for this study were from the 2015-2016, 2016-2017, and 2017-2018 Healthy Minds Study (HMS). Healthy Minds Study is a large, cross-sectional cohort study of both undergraduate and graduate students from universities and colleges across the United States and Canada. The Healthy Minds Study survey questions include assessment of demographic information, military status, self-reported eating disorder symptoms using the SCOFF questionnaire, and self-reported eating disorder diagnosis. Univariate analysis, chi-square analysis, and logistic regression with an unadjusted and covariate adjusted model were used to examine the association between eating disorder symptoms and military affiliation. These analyses were also used to examine the association between eating disorder diagnosis among those with eating disorder symptoms and military affiliation. All analyses were conducted using SPSS.

Results

The prevalence of eating disorder symptoms was high among both the civilian (20.4%) and military-involved (14.4%) students. Among females, there was a significantly higher (P value = .041) prevalence of eating disorder symptoms among civilian college students (24.7%) compared to military-involved students (21.3%). Among those with eating disorder symptoms, the prevalence of diagnosis was low in both military and civilian students. Specifically, the prevalence of diagnosis was significantly lower (P value = .032) among military-involved college students (10.8%) compared to civilian college students (16.4%). Differences in sociodemographic characteristics (e.g., gender, race/ethnicity, and age) among military-involved and civilian college students appear to explain this association.

Conclusions

The underdiagnosis of eating disorders is far too common, and this represents a threat to the health of military and civilian populations alike. Underdiagnosis of eating disorders within military environments may be due to underreporting, particularly among men and racial/ethnic minority groups.
ConsHMM Atlas: conservation state annotations for major genomes and human genetic variation
Authors: Arneson Adriana , Felsheim Brooke , Chien Jennifer , Ernst Jason
Published: March 2021

ConsHMM is a method recently introduced to annotate genomes into conservation states, which are defined based on the combinatorial and spatial patterns of which species align to and match a reference genome in a multi-species DNA sequence alignment. Previously, ConsHMM was only applied to a single genome for one multi-species sequence alignment. Here, we apply ConsHMM to produce 22 additional genome annotations covering human and seven other organisms for a variety of multi-species alignments. Additionally, we extend ConsHMM to generate allele-specific annotations, which we use to produce conservation state annotations for every possible single-nucleotide mutation in the human genome. Finally, we provide a web interface to interactively visualize parameters and annotation enrichments for ConsHMM models. These annotations and visualizations comprise the ConsHMM Atlas, which we expect will be a valuable resource for analyzing a variety of major genomes and genetic variation.
Family Matters: Education and the (Conditional) Effect of State Indoctrination in China
Authors: Kao Jay C
Published: March 2021

When and how does state indoctrination work? Building upon research on motivated reasoning and family socialization, I argue that only those individuals whose parents have connections to political patronage are subject to state indoctrination because their pro-regime biases transmitted from parents induce higher receptivity prior to government messages. Focusing on political education in China, I conduct a quasi-experimental analysis exploiting the sharp variation in textbook content generated by China’s most recent curriculum reform. Results based on a national survey show that the new politics textbooks successfully affected only those individuals whose parents had worked for the government. The finding survives extensive robustness checks and falsification tests. I also consider several alternative explanations of the effects: preference falsification, selective attention, parental indoctrination, and educational quality. This paper not only highlights the role of intergenerational transmission in moderating the effectiveness of state indoctrination but also casts doubt on the actual degree to which regimes can change minds by changing educational content.
Faster than warp speed: early attention to COVD-19 by anti-vaccine groups on Facebook
Authors: Kalichman Seth C , Eaton Lisa A , Earnshaw Valerie A , Brousseau Natalie
Published: March 2021

Background

The unprecedented rapid development of COVID-19 vaccines has faced SARS-CoV- (COVID-19) vaccine hesitancy, which is partially fueled by the misinformation and conspiracy theories propagated by anti-vaccine groups on social media. Research is needed to better understand the early COVID-19 anti-vaccine activities on social media.

Methods

This study chronicles the social media posts concerning COVID-19 and COVID-19 vaccines by leading anti-vaccine groups (Dr Tenpenny on Vaccines, the National Vaccine Information Center [NVIC] the Vaccination Information Network [VINE]) and Vaccine Machine in the early months of the COVID-19 pandemic (February–May 2020).

Results

Analysis of 2060 Facebook posts showed that anti-vaccine groups were discussing COVID-19 in the first week of February 2020 and were specifically discussing COVID-19 vaccines by mid-February 2020. COVID-19 posts by NVIC were more widely disseminated and showed greater influence than non-COVID-19 posts. Early COVID-19 posts concerned mistrust of vaccine safety and conspiracy theories.

Conclusion

Major anti-vaccine groups were sowing seeds of doubt on Facebook weeks before the US government launched its vaccine development program ‘Operation Warp Speed’. Early anti-vaccine misinformation campaigns outpaced public health messaging and hampered the rollout of COVID-19 vaccines.
Evaluating dietary acidifiers as alternatives for conventional feed-based antibiotics in nursery pig diets
Authors: Dahmer Payton L , Jones Cassandra K
Published: March 2021

A total of 360 weanling pigs (DNA 200 × 400; initially 9.7 ± 0.23 kg BW) were used in a 21-d experiment with 6 pigs/pen, 10 replicate pens/treatment, and 2 separate nursery rooms, each with 30 pens. Pigs were weighed and allotted to pens based on BW in a completely randomized block design to one of six treatment diets: 1) Negative control (no organic acids or antibiotics) and the control with 2) 0.25% acidifier A; 3) 0.3% acidifier B; 4) 0.5% acidifier C); 5) 50 g/ton carbadox; and 6) 400 g/ton chlortetracycline (CTC). Upon weaning, a common diet with no antibiotics or additives was fed for 21 d (Phases 1 and 2; days −21 to 0), followed by a 21-d experimental period (Phase 3; days 0 to 21) where treatment diets were fed. Pigs and feeders were individually weighed on a weekly basis to calculate average daily gain (ADG), average daily feed intake (ADFI), and feed efficiency (G:F). Data were analyzed using the PROC GLIMMIX procedure of SAS (v 9.4, SAS Inst., Cary, NC) with pen as the experimental unit, treatment as a fixed effect, and room as a random effect. Dietary treatment had a significant impact (P < 0.05) on ADG, ADFI, and G:F each week and for the overall experimental period (days 0 to 21). Specifically, from days 0 to 7, pigs fed CTC had increased (P = 0.001) ADG compared with those fed acidifier B, acidifier C, and carbadox, whereas pigs fed the negative control and acidifier A diets were intermediate. Additionally, pigs fed the CTC diet had improved (P = 0.0002) ADFI when compared with all other treatments. From days 7 to 14 and days 14 to 21, pigs fed the carbadox diet had decreased (P < 0.0001) ADG compared with all other treatments. During the overall period (days 0 to 21), pigs fed diets containing carbadox had reduced ADG and ADFI (P < 0.0001), whereas pigs fed CTC had improved (P < 0.0001) ADG compared with all other treatments. Additionally, blood parameters, fecal consistency, and fecal microbial populations were analyzed on a subset of pigs (n = 5 pigs/treatment). Dietary treatment significantly affected (P < 0.05) concentrations of protein, globulin, phosphorus, alkaline phosphatase, and sorbitol dehydrogenase in the blood. Treatment also significantly impacted (P = 0.0005) fecal score but did not affect (P = 0.59) fecal microbial growth from days 0 to 21. In summary, CTC continues to be a valuable additive to improve performance in the nursery. Further investigation surrounding the efficacy of dietary acidifiers as antibiotic alternatives is warranted given inconclusive evidence in this study.
Comparative genomic analysis of genogroup 1 and genogroup 2 rotaviruses circulating in seven US cities, 2014–2016
Authors: Esona Mathew D , Gautam Rashi , Katz Eric , Jaime Jose , Ward M Leanne , Wikswo Mary E , Betrapally Naga S , Rustempasic Slavica M , Selvarangan Rangaraj , Harrison Christopher J , Boom Julie A , Englund Jan , Klein Eileen J , Staat Mary Allen , McNeal Monica M , Halasa Natasha , Chappell James , Weinberg Geoffrey A , Payne Daniel C , Parashar Umesh D , Bowen Michael D
Published: March 2021

For over a decade, the New Vaccine Surveillance Network (NVSN) has conducted active rotavirus (RVA) strain surveillance in the USA. The evolution of RVA in the post-vaccine introduction era and the possible effects of vaccine pressure on contemporary circulating strains in the USA are still under investigation. Here, we report the whole-gene characterization (eleven ORFs) for 157 RVA strains collected at seven NVSN sites during the 2014 through 2016 seasons. The sequenced strains included 52 G1P[8], 47 G12P[8], 18 G9P[8], 24 G2P[4], 5 G3P[6], as well as 7 vaccine strains, a single mixed strain (G9G12P[8]), and 3 less common strains. The majority of the single and mixed strains possessed a Wa-like backbone with consensus genotype constellation of G1/G3/G9/G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1, while the G2P[4], G3P[6], and G2P[8] strains displayed a DS-1-like genetic backbone with consensus constellation of G2/G3-P[4]/P[6]/P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Two intergenogroup reassortant G1P[8] strains were detected that appear to be progenies of reassortment events between Wa-like G1P[8] and DS-1-like G2P[4] strains. Two Rotarix® vaccine (RV1) and two RV5 derived (vd) reassortant strains were detected. Phylogenetic and similarity matrices analysis revealed 2–11 sub-genotypic allelic clusters among the genes of Wa- and DS-1-like strains. Most study strains clustered into previously defined alleles. Amino acid (AA) substitutions occurring in the neutralization epitopes of the VP7 and VP4 proteins characterized in this study were mostly neutral in nature, suggesting that these RVA proteins were possibly under strong negative or purifying selection in order to maintain competent and actual functionality, but fourteen radical (AA changes that occur between groups) AA substitutions were noted that may allow RVA strains to gain a selective advantage through immune escape. The tracking of RVA strains at the sub-genotypic allele constellation level will enhance our understanding of RVA evolution under vaccine pressure, help identify possible mechanisms of immune escape, and provide valuable information for formulation of future RVA vaccines.
Digital Health Technology and Telemedicine-Based Hospital and Home Programs in Pulmonary Medicine During the COVID-19 Pandemic
Authors: Ilowite Jonathan , Lisker Gita , Greenberg Harly
Published: March 2021

Background:

The current coronavirus disease 2019 (COVID-19) pandemic has caused a significant strain on medical resources throughout the world. A major shift to telemedicine and mobile health technologies has now taken on an immediate urgency. Newly developed devices designed for home use have facilitated remote monitoring of various physiologic parameters relevant to pulmonary diseases. These devices have also enabled home-based pulmonary rehabilitation programs. In addition, telemedicine and home care services have been leveraged to rapidly develop acute care hospital-at-home programs for the treatment of mild-to-moderate COVID-19 illness.

Areas of Uncertainty:

The benefit of remote monitoring technologies on patient outcomes has not been established in robust trials. Furthermore, the use of these devices, which can increase the burden of care, has not been integrated into current clinical workflows and electronic medical records. Finally, reimbursement for these telemedicine and remote monitoring services is variable.

Data Sources:

Literature review.

Therapeutic Advances:

Advances in digital technology have improved remote monitoring of physiologic parameters relevant to pulmonary medicine. In addition, telemedicine services for the provision of pulmonary rehabilitation and novel hospital-at-home programs have been developed. These new home-based programs have been adapted for COVID-19 and may also be relevant for the management of acute and chronic pulmonary diseases after the pandemic.

Conclusion:

Digital remote monitoring of physiologic parameters relevant to pulmonary medicine and novel hospital-at-home programs are feasible and may improve care for patients with acute and chronic respiratory-related disorders.
Advances in Treatment of Sleep-Disordered Breathing
Authors: Lou Becky X , Greenberg Harly , Korotun Maksim
Published: March 2021

Background:

Sleep-disordered breathing, composed of obstructive sleep apnea (OSA) and central sleep apnea (CSA), affects millions of people worldwide carrying with it significant morbidity and mortality. Diagnosis is made by polysomnography, and severity of sleep apnea is determined by the apnea–hypopnea index (AHI). Positive airway pressure (PAP) therapy has been the gold standard in treating both OSA and CSA. PAP therapy can greatly reduce AHI burden as well as morbidity and mortality and improve quality of life.

Areas of Uncertainty:

However, patients report difficulties adhering to PAP therapy because of discomfort with mask interface, sensation of excessive pressure, and claustrophobia. Although other options exist to treat sleep apnea, such as mandibular advancement oral appliance devices, positional therapy, and surgery, these additional therapeutic modalities as current options have limitations. Emerging technology is now available to overcome hindrances to standard therapy.

Data Sources:

A literature search was performed from the following databases: PubMed, Cochrane Library (Cochrane Database of Systematic Reviews), and Cochrane Central Register of Controlled Trials, and FDA device database (clinicaltrial.gov).

Therapeutic Advances:

Other modalities of treating sleep-disordered breathing now include the hypoglossal nerve stimulator, which stimulates the hypoglossal nerve during sleep to alleviate airflow obstruction by contracting the genioglossus muscle thus treating OSA. Similarly, the phrenic nerve stimulator restores a more stable breathing pattern during sleep by stimulating the phrenic nerve to activate the diaphragm during CSA. Both nerve stimulators have been shown to reduce AHI severity and improve quality of life for patients suffering from sleep-disordered breathing.

Conclusions:

PAP therapy, although the gold standard, has limitations in the treatment of sleep apnea. New modalities such as hypoglossal nerve stimulator and phrenic nerve stimulator may help to overcome difficulties with adherence and offer new options for treatment of both obstructive and central sleep apnea.
Brain structure and function show distinct relations with genetic predispositions to mental health and cognition
Authors: Liu Shu , Smit Dirk J.A. , Abdellaoui Abdel , van Wingen Guido A. , Verweij Karin J.H.
Published: March 2021

Mental health and cognitive achievement are partly heritable. To identify the underlying neural mechanisms, we associated genetic predispositions to various mental health and cognitive traits with a large set of structural and functional brain measures from the UK Biobank (N=36,799). We show that genetic predispositions to attention deficit hyperactivity disorder, smoking initiation, and cognitive traits have stronger associations with brain structure than with brain function, whereas genetic predispositions to most other psychiatric disorders have stronger associations with brain function than with brain structure. These results reveal that genetic predispositions to mental health and cognitive traits have distinct brain profiles.
SARS-COV-2 antibody prevalence in patients on dialysis in the US in January 2021
Authors: Anand Shuchi , Montez-Rath Maria , Han Jialin , Cadden LinaCel , Hunsader Patti , Kerschmann Russell , Beyer Paul , Boyd Scott D , Garcia Pablo , Dittrich Mary , Block Geoffrey A , Parsonnet Julie , Chertow Glenn M
Published: March 2021

Background

To estimate seroprevalence of SARS-CoV-2 antibodies in the US, the country with the world’s largest absolute numbers of COVID19 cases and deaths, we conducted a cross-sectional assessment from a sample of patients receiving dialysis in January 2021.

Methods

We tested remainder plasma of 21,424 patients receiving dialysis through the third-largest US dialysis organization, with facilities located nationwide. We used the Siemens spike protein receptor binding domain total antibody assay to estimate crude SARS-CoV-2 seroprevalence, and then estimated seroprevalence for the US dialysis and adult population by standardizing by age, sex and region. We also compared January 2021 seroprevalence and case-detection rates to that from a similar subsample of patients receiving dialysis who had been tested in July 2020.

Results

Patients in the sample were disproportionately from older age and minority race/ethnic groups. Seroprevalence of SARS-CoV-2 was 18.9% (95% CI: 18.3-19.5%) in the sample, 18.7% (18.1-19.2%) standardized to the US dialysis population, and 21.3% (20.3-22.3%) standardized to the US adult population (range 15.3-20.8% in the Northeast and South respectively). Younger age groups (18-44 years), and persons self-identifying as Hispanic or living in Hispanic neighborhoods, and persons living in the poorest neighborhoods were among the subgroups with the highest seroprevalence (25.9% (24.1-27.8%), 25.1% (23.6-26.4%), 24.8% (23.2-26.5%) respectively). Compared to data from July 2020, we observed diminished variability in seroprevalence by geographic region and urban-rural status. Estimated case detection rate increased from 14% to 23% in July 2020 to January 2021.

Conclusions

A year after the first case of SARS-CoV-2 infection was detected in the US, fewer than one in four adults have evidence of SARS-CoV-2 antibodies. Vaccine roll out to majority minority neighborhoods and poorer neighborhoods will be critical to disrupting the spread of infection.

Funding

Ascend Clinical Laboratories funded remainder-plasma testing.
AI-driven prediction of SARS-CoV-2 variant binding trends from atomistic simulations
Authors: Capponi Sara , Wang Shangying , Navarro Erik J. , Bianco Simone
Published: March 2021

We present a novel technique to predict binding affinity trends between two molecules from atomistic molecular dynamics simulations. The technique uses a neural network algorithm applied to a series of images encoding the distance between two molecules in time. We demonstrate that our algorithm is capable of separating with high accuracy non-hydrophobic mutations with low binding affinity from those with high binding affinity. Moreover, we show high accuracy in prediction using a small subset of the simulation, therefore requiring a much shorter simulation time. We apply our algorithm to the binding between several variants of the SARS-CoV-2 spike protein and the human receptor ACE2.
Make Interactive Complex Heatmaps in R
Authors: Gu Zuguang , Hübschmann Daniel
Published: March 2021

Heatmap is a powerful visualization method on two-dimensional data to reveal patterns shared by subsets of rows and columns. InR, there are many packages that make heatmaps. Among them,ComplexHeatmapprovides rich tools for constructing highly customizable heatmaps. It can easily establish connections between information from multiple sources by automatically concatenating and adjusting multiple heatmaps as well as complex annotations, which makes it widely applied in data analysis in various fields, especially in Bioinformatics. Nevertheless, the limit ofComplexHeatmapstill exists. It only generates static plots which restricts deeper inspections on complex heatmaps,e.g., to look into a subset of rows and columns when a specific pattern of interest is observed from the heatmap. In this work, we described a newR/Bioconductor packageInteractiveComplexHeatmapthat brings interactivity toComplexHeatmap.InteractiveComplexHeatmapis designed with an easy-to-use interface where static complex heatmaps can be directly exported to an interactive Shiny web application only with one extra line of code. The interactive application contains comprehensive tools for manipulating heatmaps. Besides common tools as supported in other interactive heatmap packages,InteractiveComplexHeatmapadditionally supports,e.g., selecting over multiple heatmaps and searching heatmaps via row or column labels. Also,InteractiveComplexHeatmapprovides methods for exporting static heatmaps from other popular heatmap functions,e.g.,heatmap.2()orpheatmap(), to interactive heatmap applications. Finally,InteractiveComplexHeatmapprovides flexible functionalities for integrating interactive heatmap widgets into other Shiny applications.InteractiveComplexHeatmapprovides a user interface for self-defining response to the selection events on heatmaps, which helps to implement more complex Shiny web applications.
Genome-Wide Covariation in SARS-CoV-2
Authors: Cresswell-Clay Evan , Periwal Vipul
Published: March 2021

The SARS-CoV-2 virus causing the global pandemic is a coronavirus with a genome of about 30Kbase length [Song et al., 2019]. The design of vaccines and choice of therapies depends on the structure and mutational stability of encoded proteins in the open reading frames(ORFs) of this genome. In this study, we computed, using Expectation Reflection, the genome-wide covariation of the SARS-CoV-2 genome based on an alignment of ≈ 130000 SARS-CoV-2 complete genome sequences obtained from GISAID[Shu & McCauley, 2017]. We used this covariation to compute the Direct Information between pairs of positions across the whole genome, investigating potentially important relationships within the genome, both within each encoded protein and between encoded proteins. We then computed the covariation within each clade of the virus. The covariation detected recapitulates all clade determinants and each clade exhibits distinct covarying pairs.
Sexual conflict promotes species coexistence through negative frequency dependence
Authors: Gomez-Llano Miguel , Nilén Sofie , Moodie Iain , Svensson Erik I.
Published: March 2021

A major challenge in community ecology is to understand the mechanisms promoting stable local coexistence. A necessary feature of local coexistence is that species show negative frequency dependence, rescuing rare species from exclusion. However, most studies have focused on ecological differences driving negative frequency dependence, ignoring non-ecological mechanisms such as reproductive interactions. Here, we combined field studies with behavioural and mesocosm experiments to investigate how reproductive interactions within and between species promote coexistence. Our results indicate that the intensity of male mating harassment and sexual conflict increases as species become more common, reducing female productivity and leading to negative frequency dependence. Moreover, field surveys reveal that negative frequency dependence operates in natural settings, consistent with our experimental results. These results suggest that sexual conflict can promote local coexistence and highlights the importance of studying reproductive interactions together with ecological differences to better understand the mechanisms promoting species coexistence.

Significance statement

Research on the mechanisms promoting local species coexistence have focused on canonical ecological differences that increase intraspecific over interspecific competition. However, one intrinsic factor of species that can promote coexistence are the reproductive interactions. We performed a series of behavioural and mesocosm experiments manipulating species frequencies together with field observations and show that sexual conflict can decrease female fitness when species are common and promote local coexistence. Our results suggest that reproductive interactions are an understudied mechanism that can promote species coexistence even when species are ecologically equivalent.
Silkworm spinning: the programmed self-assembly from natural silk fibroin to superfibre
Authors: Song Kai , Wang Yejing , Dong Wenjie , Li Zhenzhen , He Huawei , Zhu Ping , Xia Qingyou
Published: March 2021

Silkworm silk is one of the best natural protein fibers spun by the silkworm at ambient temperature and pressure using aqueous silk protein solution. It is a great challenge to reproduce high-performance artificial fibers comparable to natural silk by bionics for the incomplete understanding of silkworm spinning mechanism, especially the structure and assembly of natural silk fibroin (NSF) in the silk gland. Here, we studied the structure and assembly of NSF with the assistance of amphipol and digitonin. Our results showed NSFs were present as nanofibrils primarily composed of random coils in the silk gland. Metal ions were vital for the formation of NSF nanofibrils. The successive decrease in pH from posterior silk gland (PSG) to anterior silk gland (ASG) resulted in a gradual increase in NSF hydrophobicity. NSF nanofibrils were randomly arranged from PSG to ASG-1, and then self-assembled into herringbone-like patterns near the spinneret (ASG-2) ready for silkworm spinning. Our study reveals the mechanism by which silkworms cleverly utilize metal ions and pH gradient in the silk gland to drive the programmed self-assembly of NSF from disordered nanofibrils to anisotropic liquid crystalline spinning dope (herringbone-like patterns) for silkworm spinning, thus providing novel insights into silkworm/spider spinning mechanism and bionic creation of high-performance fibers.
G-quadruplex RNA motifs influence gene expression in the malaria parasitePlasmodium falciparum
Authors: Dumetz Franck , Chow Eugene Yui-Ching , Harris Lynne M. , Umar Mubarak I. , Jensen Anders , Chung Betty , Chan Ting Fung , Merrick Catherine J. , Kwok Chun Kit
Published: March 2021

G-quadruplexes are non-helical secondary structures that can foldin vivoin both DNA and RNA. In human cells, they can influence replication, transcription and telomere maintenance in DNA, or translation, transcript processing and stability of RNA. We have previously showed that G-quadruplexes are detectable in the DNA of the malaria parasitePlasmodium falciparum, despite a very highly A/T-biased genome with unusually few guanine-rich sequences. Here, we show that RNA G-quadruplexes can also form inP. falciparumRNA, using rG4-seq for transcriptome-wide structure-specific RNA probing. Many of the motifs, detected here via the rG4seeker pipeline, have non-canonical forms and would not be predicted by standardin silicoalgorithms. However,in vitrobiophysical assays verified the formation of non-canonical motifs. The G-quadruplexes in theP. falciparumtranscriptome are frequently clustered in certain genes and associated with regions encoding low-complexity peptide repeats. They are overrepresented in particular classes of genes, notably those that encodePfEMP1 virulence factors, stress response genes and DNA binding proteins.In vitrotranslation experiments andin vivomeasures of translation efficiency showed that G-quadruplexes can influence the translation ofP. falciparummRNAs. Thus, the G-quadruplex is a novel player in post-transcriptional regulation of gene expression in this major human pathogen.
Full-length native CGRP neuropeptide and its stable analogue SAX, but not CGRP peptide fragments, inhibit mucosal HIV-1 transmission
Authors: Bomsel Morgane , Sams Anette , Cohen Emmanuel , Sennepin Alexis , Siracusano Gabriel , Sanvito Francesca , Edvinsson Lars , Lopalco Lucia , Ganor Yonatan
Published: March 2021

The vasodilator neuropeptide calcitonin gene-related peptide (CGRP) plays both detrimental and protective roles in different pathologies. CGRP is also an essential component of the neuro-immune dialogue between nociceptors and mucosal immune cells. We previously reported that CGRP strongly inhibits human immunodeficiency virus type 1 (HIV-1) infection, by suprresing Langerhans cells (LCs)-mediated HIV-1 transfer to T-cells during trans-infection. To understand the requirements for CGRP receptor (CGRP-R) activation during inhibition of HIV-1 transmission, we here investigated the anti-HIV-1 activities of full-length native CGRP and its recently developed stable analogue SAX, as well as several CGRP peptide fragments containing its binding C-terminal and activating N-terminal regions. We show that SAX significantly inhibits LCs-mediated HIV-1 trans-infection but with lower potency than CGRP, while all CGRP peptide fragments tested have no effect. In addition, CGRP readily enters the epithelial compartment of mucosal tissues and does not modify the distribution and density of mucosal immune cells.In-vivo, a single CGRP treatment in humanized mice, before vaginal challenge with high-dose HIV-1, restricts the increase in plasma viral load and maintains higher CD4+ T-cell counts. Together, our results call for the optimization and design of CGRP analogues and agonists, which could be harnessed for prevention of mucosal HIV-1 transmission.
The force loading rate drives cell mechanosensing through both reinforcement and fluidization
Authors: Andreu Ion , Falcones Bryan , Hurst Sebastian , Chahare Nimesh , Quiroga Xarxa , Roux Anabel-Lise Le , Kechagia Zanetta , Beedle Amy E.M. , Elósegui-Artola Alberto , Trepat Xavier , Farré Ramon , Betz Timo , Almendros Isaac , Roca-Cusachs Pere
Published: March 2021

Cell response to force regulates essential processes in health and disease. However, the fundamental mechanical variables that cells sense and respond to remain unclear. Here we show that the rate of force application (loading rate) drives mechanosensing, as predicted by a molecular clutch model. By applying dynamic force regimes to cells through substrate stretching, optical tweezers, and atomic force microscopy, we find that increasing loading rates trigger talin-dependent mechanosensing, leading to adhesion growth and reinforcement, and YAP nuclear localization. However, above a given threshold the actin cytoskeleton undergoes fluidization and softens, decreasing loading rates and preventing reinforcement. By stretching rat lungsin vivo, we show that a similar phenomenon occurs at the organ level. Our results show that cell sensing of external forces and of passive mechanical parameters (like tissue stiffness) can be understood through the same mechanisms, driven by the properties under force of the mechanosensing molecules involved.
Mixed fatty acid-phospholipid protocell networks
Authors: Põldsalu Inga , Köksal Elif Senem , Gözen Irep
Published: March 2021

Self-assembled membranes composed of both fatty acids and phospholipids are both permeable for solutes and structurally stable, which was likely an advantageous combination for the development of primitive cells on the early Earth. Here we report on the solid surface-assisted formation of primitive mixed-surfactant membrane compartments,i.e.model protocells, from multilamellar lipid reservoirs composed of different ratios of fatty acids and phospholipids. Similar to the previously discovered enhancement of model protocell formation on solid substrates, we achieve spontaneous multi-step self-transformation of mixed surfactant reservoirs into closed surfactant containers, interconnected via nanotube networks. Some of the fatty acid containing compartments in the networks exhibit colony-like growth. We demonstrate that the compartments generated from fatty acid-containing phospholipid membranes feature increased permeability coefficients for molecules in the ambient solution, for fluorescein up to 7*10-6cm/s and for RNA up to 3.5*10-6cm/s. Our findings indicate that surface-assisted autonomous protocell formation and development, starting from mixed amphiphiles, is a plausible scenario for the early stages of the emergence of primitive cells.
Boundary convection during velocity sedimentation in the Optima analytical ultracentrifuge
Authors: Berkowitz Steven A. , Laue Thomas
Published: March 2021

Analytical ultracentrifugation (AUC) provides the most widely applicable, precise and accurate means for characterizing solution hydrodynamic and thermodynamic properties. In recent times AUC has found broad application in the biopharmaceutical industry as a first-principle means for quantitatively characterizing biopharmaceuticals. Boundary sedimentation velocity AUC (SV-AUC) analysis is widely used to assess protein aggregation, fragmentation and conformational variants in the same solvents used during drug development and production. SV-AUC is especially useful for the analysis of drug substance, drug product and dosing solution, where other techniques may exhibit solvent matrix issues or concentration limitations. Recently, the only manufacturer of the analytical ultracentrifuge, released its newest (third generation) analytical ultracentrifuge, the Optima, in early 2017 to replace its aging 2ndgeneration XL series ultracentrifuges. However, SV-AUC data from four Optima units used in conducting characterization work on adeno-associated virus (AAV) has shown evidence of sample convection. Further investigation reveals that this problem arises from the temperature control system design, which is prone to producing destabilizing temperature induced density gradients that can lead to density inversions. The observed convection impacts both the qualitative and quantitative data generated by the Optima. The problem is intermittent and variable in severity within a given Optima unit and between Optima units. This convection appears to be mainly associated with low rotor speeds and dilute samples in dilute solvents, such as AAV samples in formulation buffers containing relatively low concentrations of salts, sugars, etc. Under these conditions it is found that a sufficiently robust stabilizing density gradient is not always present during sedimentation, making the sample susceptible to convection by localized density inversions. Because SV-AUC is used as an analytical tool in making critical decisions in the development and quality control of biotherapeutics, it is imperative to alert users about this potential problem. In general special attention to data quality needs to be made by those researchers working with very large biopharmaceutical particles (e.g. gene therapy products that involve viral vectors or nanoparticles), where the conditions leading to convection are most likely to occur. It is important to note that the XL series analytical ultracentrifuges do not suffer from this problem, indicating that this problem is unique to the Optima. Attributes that reveal the presence of this problem and strategies for its elimination or minimization are provided.
Optimizing mechanostable anchor points of engineered lipocalin in complex with CTLA-4
Authors: Liu Zhaowei , Moreira Rodrigo A. , Dujmović Ana , Liu Haipei , Yang Byeongseon , Poma Adolfo B. , Nash Michael A.
Published: March 2021

We used single-molecule AFM force spectroscopy (AFM-SMFS) to screen residues along the backbone of a non-antibody protein binding scaffold (lipocalin/anticalin), and determine the optimal anchor point that maximizes binding strength of the interaction with its target (CTLA-4). By incorporating non-canonical amino acids into anticalin, and using click chemistry to attach an Fgβ peptide at internal sequence positions, we were able to mechanically dissociate anticalin from CTLA-4 by pulling from eight different anchoring residues using an AFM cantilever tip. We found that pulling on the anticalin from residue 60 or 87 resulted in significantly higher rupture forces and a decrease inkoffby 2-3 orders of magnitude over a force range of 50-200 pN. Five of the six internal pulling points tested were significantly more stable than N- or C-terminal anchor points, rupturing at up to 250 pN at loading rates of 0.1-10 nN sec-1. Anisotropic network modelling and molecular dynamics simulations using the Gō-MARTINI approach explained the mechanism underlying the geometric dependency of mechanostability. These results suggest that optimization of attachment residue position for therapeutic and diagnostic cargo can provide large improvements in binding strength, allowing affinity maturation without requiring genetic mutation of binding interface residues.
Metabolic breakdown of non-small cell lung cancers by mitochondrial HSPD1 targeting
Authors: Parma Beatrice , Ramesh Vignesh , Gollavilli Paradesi Naidu , Siddiqui Aarif , Pinna Luisa , Schwab Annemarie , Marschall Sabine , Zhang Shuman , Pilarsky Christian , Napoli Francesca , Volante Marco , Urbanczyk Sophia , Mielenz Dirk , Daa Schrøder Henrik , Stemmler Marc , Wurdak Heiko , Ceppi Paolo
Published: March 2021

The identification of novel targets is of paramount importance to develop more effective drugs and improve the treatment of non-small cell lung cancer (NSCLC), the leading cause of cancer-related deaths worldwide. Since cells alter their metabolic rewiring during tumorigenesis and along cancer progression, targeting key metabolic players and metabolism-associated proteins represents a valuable approach with a high therapeutic potential. Metabolic fitness relies on the functionality of heat shock proteins (HSPs), molecular chaperones that facilitate the correct folding of metabolism enzymes and their assembly in macromolecular structures. Here, we show HSPD1 (HSP60) as a survival gene ubiquitously expressed in NSCLC and associated with poor patients’ prognosis. HSPD1 knockdown or its chemical disruption by the small molecule KHS101 induces a drastic breakdown of oxidative phosphorylation, and suppresses cell proliferation both in vitro and in vivo. By combining drug profiling with transcriptomics and through a whole-genome CRISPR/Cas9 screen, we demonstrate that HSPD1-targeted anti-cancer effects are dependent on OXPHOS and validated molecular determinants of KHS101 sensitivity, in particular, the creatine-transporter SLC6A8 and the subunit of the cytochrome c oxidase complex COX5B. These results highlight mitochondrial metabolism as an attractive target and HSPD1 as a potential theranostic marker for developing therapies to combat NCSLC.

Significance

HSPD1 elimination or disruption interferes with NSCLC metabolic activity causing a strong OXPHOS-dependent energetic breakdown, which the cancer cells fail to overcome, highlighting HSPD1 as a potential theranostic marker for improving lung cancer therapy.
Corporate governance, internal audit quality and financial reporting quality of financial institutions
Authors: Kaawaase Twaha Kigongo , Nairuba Catherine , Akankunda Brendah , Bananuka Juma
Published: March 2021

Purpose

The purpose of this study is to establish the relationship between corporate governance attributes (board expertise, board independence and board role performance), internal audit quality and financial reporting quality using evidence from Uganda's financial institutions.

Design/methodology/approach

This study research design is cross sectional and correlational. The study used a questionnaire survey of Chief Finance Officers, Senior Accountants and Internal audit managers of financial institutions in Uganda. Data were analyzed with the help of Statistical Package for Social Sciences.

Findings

Results indicate that board expertise and board role performance are significantly associated with financial reporting quality. Also, internal audit quality is significantly associated with financial reporting quality. Board independence is not a significant predictor of financial reporting quality.

Originality/value

This paper provides insights of what matters for financial reporting quality in Uganda's financial reporting quality. It uses the qualitative characteristics of financial statements to measure financial reporting quality. This paper focuses mainly on the conceptual framework developed by the International Accounting Standards Board.
Has the dependence structure of the BRICS exchange rates changed after the financial crisis? Evidence from R-Vine copula model
Authors: Zhang Zhuoqun , Zhang Tao
Published: March 2021

Purpose

The authors examine the dependence structure of the BRICS exchange rates.

Design/methodology/approach

The authors construct a regular vine copula model to study the co-movements of exchange rates in BRICS controlling the influences from the SDR currencies and the oil prices.

Findings

The main findings show that, after the financial crisis, RMB pursued a more balanced strategy shifting from USD-centered to USD-EUR dependency and the oil prices become more dependent on RUB than USD, which could weaken the dollar hegemony. From robustness tests, we find that the inclusion of RMB in SDR has certain but limited impacts on the dependence structure and the influence of the GBP weakened as well. The results have important implications for currency trade, policy design and the future of the BRICS.

Originality/value

The contribution of this paper is twofold. First, we examine the interdependence structure of the BRICS exchange rates controlling for the influence of SDR currencies and the oil prices with R-Vine copula model. Second, we compare the pre- and after-crisis structure and see if the financial crisis and the BRICS summits have changed the structure.