bluuebunny/crossref_metadata_2025 huggingface dataset:
Current practices, facilitators, and barriers experienced by program providers implementing the National Diabetes Prevention Program in Los Angeles County
Authors: Green Gabrielle , DeFosset Amelia R , Sivashanmugam Megala , Mosst Jennifer , Kuo Tony
Published: April 2020

Individuals with prediabetes can lower their diabetes risk by participating in the National Diabetes Prevention Program (National DPP), an evidence-based, group lifestyle change program that is taught by a certified lifestyle coach. To date, studies have not explicitly compared National DPP implementation across multiple settings (i.e., types of organizations) to understand comparative setting advantages or challenges to engaging priority groups. The purpose of this study was to gain an in-depth understanding of: (a) the variation in National DPP implementation across clinic, community-based, and digital settings and (b) associated facilitators and barriers. The study focused on three core implementation domains: recruitment, retention, and data reporting. This study used a descriptive, qualitative approach to identify current practices, facilitators, and barriers to National DPP implementation by conducting semistructured key informant interviews in spring 2018 with 12 organizations delivering the National DPP in Los Angeles County. There was a general commonality between in-person settings (clinics and community-based), while the experiences of digital providers were relatively distinct. Recruitment and retention were widely described by all settings as labor- and time-intensive, while data reporting was seen as relatively less burdensome. All respondents reported using multiple recruitment strategies. Lifestyle coaches were seen as key to retention, and they spent substantial time engaging with participants outside of class, which often was not accounted for in program costs. Data reporting was easier for organizations that invested in sophisticated data management systems and had staff with sufficient data experience. This study advances knowledge around the translation of the National DPP in diverse settings in the nation’s largest county and highlights opportunities for targeted, setting-specific support.
Larval chaetotaxy and morphology are highly homoplastic yet phylogenetically informative in Hydrobiusini water scavenger beetles (Coleoptera: Hydrophilidae)
Authors: Archangelsky Miguel , Martínez Román Nicolás Rafael , Fikáček Martin
Published: April 2020

Phylogenetic analyses testing the monophyly of the tribe Hydrobiusini and the relationships among its genera are performed based on a data matrix including characters of larval morphology and morphometrics, larval chaetotaxy and adult morphology, including eight of the nine hydrobiusine genera plus 15 outgroup taxa. The head chaetotaxy of six genera of the tribe Hydrobiusini is described (Ametor, Hybogralius, Hydramara, Limnohydrobius, Limnoxenus and Sperchopsis). Morphometric characters derived from the head capsule and mouthparts are included. All characters are illustrated in detail. The analyses performed on the above datasets and their combinations reveal the monophyly of the Hydrobiusini except for Hybogralius, and reconstruct the internal topology of the tribe, largely corresponding to results of previous molecular analyses. Hybogralius groups with genera having larvae adapted to underwater feeding in all analyses. The position of the genus Tritonus within the Laccobiini is questioned by our analyses, which suggest a closer relationship with the tribes Hydrophilini or Hydrobiusini. Larval characters are revealed as highly homoplastic, with chaetotaxic characters performing slightly worse than usual larval morphology. Nonetheless, they are phylogenetically informative and useful for testing phylogenetic hypotheses resulting from analyses of molecules or adult morphology. A key to larvae of the genera of the Hydrobiusini is presented.
Quantifying the Effects of Temperature and Relative Humidity on the Development of Wheat Blast Incited by the Lolium Pathotype of Magnaporthe oryzae
Authors: Mills Karasi B. , Madden Laurence V. , Paul Pierce A.
Published: April 2020

The Triticum pathotype of Magnaporthe oryzae (MoT) that causes wheat blast has not yet been reported in the U.S., but the closely related M. oryzae Lolium pathotype (MoL), also capable of inciting blast, is found in several wheat growing regions. Since the epidemiology of MoL-incited wheat blast is unknown, it is difficult to project where and under what conditions this pathogen may be of importance. To quantify conditions favorable for MoL infection and temporal development of wheat blast, separate cohorts of wheat spikes were spray or point inoculated at anthesis and immediately subjected to different combinations of temperature (TEMP; 20, 25, and 30°C) and 100% relative humidity (RH) duration (0, 3, 6, 12, 24, and 48 h). Blast developed under all tested conditions, with both incidence (INC) and severity (SEV) increasing over time. The effects of TEMP on angular-transformed INC and SEV (arcINC and arcSEV) were significant (P < 0.05) in most cases, with the magnitude of the TEMP effect influenced by RH duration when spikes were spray-inoculated. Between 12 and 21 days after inoculation (DAI), there were significant, positive linear relationships between hours of high RH and arcINC and arcSEV at 25 and 30°C, but not at 20°C. The estimated rates of increase in transformed INC or SEV per hour increase in high RH duration were significantly higher at 30°C than at 25°C at 12 to 14 DAI, but not at 19 to 21 DAI. The highest estimated temporal rates of increase in INC and SEV and the shortest estimated incubation periods (5 to 8 days) occurred at 25 and 30°C, with 24 and 48 h of high RH immediately after inoculation. These results will contribute to ongoing efforts to better understand the epidemiology of wheat blast incited by MoL as well as MoT.
Bayesian Adaptive Clinical Trials for Anti-Infective Therapeutics during Epidemic Outbreaks
Authors: Xu Qingyang , Chaudhuri Shomesh , Xiao Danying , Lo Andrew W.
Published: April 2020

In the midst of epidemics such as COVID-19, therapeutic candidates are unlikely to be able to complete the usual multi-year clinical trial and regulatory approval process within the course of an outbreak. We apply a Bayesian adaptive patient-centered model—which minimizes the expected harm of false positives and false negatives—to optimize the clinical trial development path during such outbreaks. When the epidemic is more infectious and fatal, the Bayesian-optimal sample size in the clinical trial is lower and the optimal statistical significance level is higher. For COVID-19 (assuming a static R0 = 2 and initial infection percentage of 0.1%), the optimal significance level is 7.1% for a clinical trial of a non-vaccine anti-infective therapeutic clinical trial and 13.6% for that of a vaccine. For a dynamic R0 ranging from 2 to 4, the corresponding values are 14.4% and 26.4%, respectively. Our results illustrate the importance of adapting the clinical trial design and the regulatory approval process to the specific parameters and stage of the epidemic.
A Robust and Reproducible Connectome Fingerprint of Ketamine is Highly Associated with the Connectomic Signature of Antidepressants
Authors: Abdallah Chadi G. , Ahn Kyung-Heup , Averill Lynnette A. , Nemati Samaneh , Averill Christopher L. , Fouda Samar , Ranganathan Mohini , Morgan Peter T. , D’Souza Deepak C. , Mathalon Daniel H. , Krystal John H. , Driesen Naomi R.
Published: April 2020

Over the past decade, various N-Methyl-D-Aspartate modulators have failed in clinical trials, underscoring the challenges of developing novel rapid-acting antidepressants based solely on the receptor or regional targets of ketamine. Thus, identifying the effect of ketamine on the brain circuitry and networks is becoming increasingly critical. In this longitudinal functional magnetic resonance imaging study of data from 265 participants, we used a validated predictive model approach that allows the full assessment of brain functional connectivity, without the need for seed selection or connectivity summaries. First, we identified a connectome fingerprint (CFP) in healthy participants (Cohort A, n=25) during intravenous infusion of a subanesthetic dose of ketamine, compared to normal saline. We then demonstrated the robustness and reproducibility of the discovered Ketamine CFP in two separate healthy samples (Cohort B, n=22; Cohort C, n=18). Finally, we investigated the Ketamine CFP connectivity at 1-week post treatment in major depressive disorder patients randomized to 8 weeks of sertraline or placebo (Cohort D, n=200). We found a significant, robust, and reproducible Ketamine CFP, consistent with reduced connectivity within the primary cortices and within the executive network, but increased connectivity between the executive network and the rest of the brain. Compared to placebo, the Ketamine CFP connectivity changes at 1-week predicted response to sertraline at 8-weeks. In each of Cohort A-C, ketamine significantly increased connectivity in a previously identified Antidepressant CFP. Investigating the brain connectivity networks, we successfully identified a robust and reproducible ketamine biomarker that is related to the mechanisms of antidepressants.

Graphical Abstract
Safety and efficacy of three-cavity clearance in the management of cryptoglandular perianal abscess: A multicentre randomized controlled study
Authors: Zhang Xin-Yi , Chen Cheng , Wei Ping , Wang Yu-Yao , Ji Li-Jiang , Zhang Qiong , Zhang Chun-Xia , Jin Hei-Ying
Published: April 2020

OBJECTIVE

To evaluate the safety and efficacy of three-cavity clearance in the management of cryptoglandular perianal abscess.

METHOD

This was a multicentre randomized controlled study. The study was designed and approved by the ethics committee of the Second Affiliated Hospital of Nanjing University of Traditional Chinese Medicine. The study was registered in the Chinese Clinical Trial Register centre (ChiCTR1800016958).Patients with cryptoglandular perianal abscess in 5 Hospitals from Sept.2018 to Sept. 2019 were included.The anal fistula rate, anal incontinence, abscess recurrence, success rate, postoperative pain, wound healing time, and hospitalization duration were compared.

RESULTS

Total 334 patients were enrolled in the study, who were 162 in the three-cavity clearance group and 172 in the control group. The anal fistula rate and abscess recurrence rate were 6.2% and 1.9% in the three-cavity clearance group (P=0.001) and 18.0% and 8.1% in the control group (P=0.009). No patients experienced fecal incontinence. The success rate in the three-cavity clearance group was 92.0% and that in the control group was 73.8% (P=0.00001). The postoperative pain on day 3 was lower in the three-cavity clearance group than that in the control group (P=0.002). The hospitalization duration was 9.0±5.4 days in the three-cavity clearance group and 10.4±6.1days in the control group (P=0.049). The wound healing time was 27.1±16.4 days in the three-cavity clearance group and 28.2±14.1 days in the control group (P=0.764).

CONCLUSIONS

This randomized controlled study showed that three-cavity clearance is a safe and effective management of cryptoglandular perianal abscess.
A Preliminary Assessment of Novel Coronavirus (COVID-19) Knowledge and Perceptions in Nigeria
Authors: Olapegba P.O. , Ayandele O. , Kolawole S.O. , Oguntayo R. , Gandi J.C. , Dangiwa A.L. , Ottu I.F.A. , Iorfa S.K.
Published: April 2020

This study assessed knowledge and perceptions about COVID-19 among the general public in Nigeria during the initial week of the pandemic lockdown in the country. From March 28 to April 4, 2020, this cross-sectional survey used an anonymous online questionnaire to collect data from respondents within Nigeria. Purposive and snowball sampling techniques were used to recruit 1357 respondents, aged 15-70 years, from 180 cities and towns within Nigeria. Study data were analysed using descriptive statistics. Approximately more than half (57.02%) of the respondents were male with high level of education (48.86% bachelor’s degree or higher). Approximately half of the respondents (46.94%) opined that COVID-19 was “a biological weapon designed by the Chinese government.” About 94% of the respondents identified “contact with airborne droplets via breathing, sneezing, or coughing” as the most common mode of transmission; most respondents associated COVID-19 with coughing (81.13%), shortness of breath (73.47%) and fever (62.79%). “Regular hand washing and social distancing” was selected by most respondents (94.25%) as a way of preventing infection whereas 11.86% reported “consuming gins, garlic, ginger, herbal mixtures and African foods/soups” as preventive measures against COVID-19. Majority of the respondents (91.73%) thought COVID-19 is deadly; and most respondents (84.3%) got 4 or more answers correctly. It was also observed that the traditional media (TV/Radio) are the most common source of health information about COVID-19 (93.5%). Findings revealed that Nigerians have relatively high knowledge, mostly derived from traditional media, about COVID-19. Their perceptions of COVID-19 bear implications across public health initiatives, compliance with precautionary behavior as well as bilateral relations with foreign nations. Evidence-based campaign should be intensified to remove misconceptions and promote precautionary measures.
Cardiac or Infectious? Transfer Learning with Chest X-Rays for ER Patient Classification
Authors: Stubblefield Jonathan , Hervert Mitchell , Causey Jason , Qualls Jake , Dong Wei , Cai Lingrui , Fowler Jennifer , Bellis Emily , Walker Karl , Moore Jason H. , Nehring Sara , Huang Xiuzhen
Published: April 2020

One of the challenges with urgent evaluation of patients with acute respiratory distress syndrome (ARDS) in the emergency room (ER) is distinguishing between cardiac vs infectious etiologies for their pulmonary findings. We evaluated ER patient classification for cardiac and infection causes with clinical data and chest X-ray image data. We show that a deep-learning model trained with an external image data set can be used to extract image features and improve the classification accuracy of a data set that does not contain enough image data to train a deep-learning model. We also conducted clinical feature importance analysis and identified the most important clinical features for ER patient classification. This model can be upgraded to include a SARS-CoV-2 specific classification with COVID-19 patients data. The current model is publicly available with an interface at the web link: http://nbttranslationalresearch.org/.

Data statement

The clinical data and chest x-ray image data for this study were collected and prepared by the residents and researchers of the Joint Translational Research Lab of Arkansas State University (A-State) and St. Bernards Medical Center (SBMC) Internal Medicine Residency Program. As data collection is on-going for the project stage-II of clinical testing, raw data is not currently available for data sharing to the public.

Ethics

This study was approved by the St. Bernards Medical Center’s Institutional Review Board (IRB).
Effect of various decontamination procedures on disposable N95 mask integrity and SARS-CoV-2 infectivity
Authors: Smith Jeffrey S. , Hanseler Haley , Welle John , Rattray Rogan , Campbell Mary , Brotherton Tacy , Moudgil Tarsem , Pack Thomas F. , Wegmann Keith , Jensen Shawn , Jin Justin , Bifulco Carlo B. , Prahl Scott A. , Fox Bernard A. , Stucky Nicholas L.
Published: April 2020

The COVID-19 pandemic has created a high demand on personal protective equipment, including disposable N95 masks. Given the need for mask reuse, we tested the feasibility of vaporized hydrogen peroxide (VHP), ultraviolet light (UV), and ethanol decontamination strategies on N95 mask integrity and the ability to remove the infectious potential of SARS-CoV-2. FIT test data showed functional degradation by both ethanol and UV decontamination to different degrees. VHP treated masks showed no significant change in function after two treatments. We also report a single SARS-CoV-2 virucidal experiment using Vero E6 cell infection. We hope our data will guide further research for evidenced-based decisions for disposable N95 mask reuse and help protect caregivers from SARS-CoV-2 and other pathogens.
Self-Collected Oral Fluid and Nasal Swabs Demonstrate Comparable Sensitivity to Clinician Collected Nasopharyngeal Swabs for Covid-19 Detection
Authors: Kojima N , Turner F , Slepnev V , Bacelar A , Deming L , Kodeboyina S , Klausner JD
Published: April 2020

Background

Currently, there is a pandemic caused by the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes Covid-19. We wanted to compare specimen types and collection methods to explore if a simpler to collect specimen type could expand access to testing.

Methods

We recruited individuals recently tested for SARS-CoV-2 infection through a “drive-through” testing program. In participants’ homes, we assessed the performance of self-collected oral fluid swab specimens with and without clinician supervision, clinician-supervised self-collected mid-turbinate (nasal) swab specimens, and clinician-collected nasopharyngeal swab specimens. We tested specimens with a validated reverse transcription-quantitative polymerase chain reaction assay for the detection of SARS-CoV-2 and measured cycle threshold values. Symptom status and date of onset of symptoms was also recorded for each participant.

Results

We recruited 45 participants. The median age of study participant was 42 years old (Interquartile range, 31 to 52 years). Of the participants, 29 had at least one specimen test positive for SARS-CoV-2. Of those, 21 (73%) of 29 reported active symptoms. By specimen type and home-based collection method, clinician-supervised self-collected oral fluid swab specimens detected 26 (90%) of 29 infected individuals, clinician-supervised self-collected nasal swab specimens detected 23 (85%) of 27, clinician-collected posterior nasopharyngeal swab specimens detected 23 (79%) of 29, and unmonitored self-collected oral fluid swab specimens detected 19 (66%) of 29. Despite nasopharyngeal swabs being considered the gold standard, 4 participants tested negative by clinician-collected nasopharyngeal swab and positive by the 3 other specimen types. Additionally, false negative results by each sample type were seen to generally not overlap.

Conclusions

Supervised self-collected oral fluid and nasal swab specimens performed similarly to, if not better than clinician-collected nasopharyngeal swab specimens for the detection of SARS-CoV-2 infection. No sample type captured all SARS-CoV-2 infections, suggesting potential heterogeneity in the distribution of viral load in different parts of the respiratory tract between individuals. Supervised self-collection performed comparably to clinician collection and would allow for rapid expansion of testing capacity in the United States by reducing the need for trained healthcare workers, reducing exposure of healthcare workers, and reducing the amount of PPE (personal protective equipment) being used for testing during a critical shortage.
Prevalence and spectrum of diabetic peripheral neuropathy and its correlation with insulin resistance - An experience from eastern India
Authors: Majumdar Manidipa , Banerjee Mainak , Sengupta Jinesh , Deb Soudeep , Jana Chanchal Kr. , Roy Biman Kanti
Published: April 2020

AIMS

Diabetes mellitus is a public health problem worldwide, with diabetic neuropathy (DN) being a common complication. Studies indicate that, neurons can develop insulin resistance (IR) and cannot respond to the neurotrophic properties of insulin. Although studies exist on the relation between DN and glycemic exposure index (GEi), papers about correlation of DN with IR is rare. This study focused on the prevalence of neuropathies in DM patients and usefulness of IR as a marker of DN.

METHODS

A cross sectional observational study was done. All patients satisfying American Diabetes Association criteria and none of the exclusion criteria were included. Total sample size was 142. Main parameters studied were glycemic status, neurological examination and nerve conduction study findings. Dyck grading was used for severity of distal symmetric polyneuropathy (DSPN). For statistical analysis, logistic and ordinal logistic regressions were used as appropriate.

RESULTS

34.5% of the sample had DN, the commonest type being DSPN (72.9%). The study population was equally divided in terms of gender and 88.7% were type 2 diabetic. About 62.5% neuropathic cases were asymptomatic. Occurrence of DN correlated significantly with duration of diabetes, FBS and IR. Age, when adjusted for other risk factors was not significantly correlated to neuropathy. The severity of DSPN correlated significantly with GEi but not with IR.

CONCLUSIONS

The prevalence of neuropathy was found to be similar to earlier western studies. This paper further establishes IR as a significant predictor for existence of DN, but it may not affect the progress of the neuropathy.
The clinical characteristics and mortal causes analysis of COVID-19 death patients
Authors: Guo Ao-Xiang , Cui Jia-Jia , OuYang Qian-Ying , He Li , Guo Cheng-Xian , Yin Ji-Ye
Published: April 2020

Purpose

Currently, COVID-19 is causing a large number of deaths globally. However, few researches focused on the clinical features of death patients. This study conducted a retrospective analysis of clinical characteristics and mortal causes in Chinese COVID-19 death patients.

Patients and methods

The clinical characteristics of death patients were collected from publicized by local health authorities in China. Expressions of virus targets in human organs were obtained from GTEx database.

Results

159 patients from 24 provinces in China were recruited in our study, including 26 young patients under 60 and 133 aged 60 or older. The median age was 71 years, which indicated that most death patients were elderly. More male patients died of COVID-19 than females (1.65 fold). Hypertension was the most common coexisting disorder and respiratory failure was the most common direct cause of death. Fever (71.19%) and cough (55.08%) were the predominant presenting symptoms. There was one asymptomatic patient. In addition, by comparing young and old patients, heart disease was identified as an important risk factor for death in the aged patients. ACE2 and TMPRSS2 were the targets of SARS-CoV-2, we analyzed their expression in different organs. TMPRSS2 and ACE2 had a high expression in the organs which had corresponding clinical features in death patients.

Conclusion

Male, age and heart disease were the main risk factors of death. Beside, asymptomatic patients with serious coexisting disorders may also die of SARS-CoV-2. Thus, more attention should be paid to the old patients with heart disease and asymptomatic patients in the treatment.
Clinical characteristics of 34 COVID-19 patients admitted to ICU in Hangzhou, China
Authors: Zheng Yi , Sun Lijun , Xu Mi , Pan Jian , Zhang Yuntao , Fang Xueling , Fang Qiang , Cai Hongliu
Published: April 2020

Introduction

The purpose of the study was to summarize the clinical and laboratory characteristics of the coronavirus disease 2019 patients admitted to intensive care unit.

Methods

We tracked the data until March 5, 2020. The cases in our cohort were divided into cases only received noninvasive ventilation (NIV) and cases required invasive mechanical ventilation (IMV). The characteristics between the two groups were compared.

Results

34 cases were included in the study. The complications rate (including, acute liver injury, acute cardiac injury and acute kidney injury) were higher in IMV cases. Lymphocytopenia and neutrophilia occurred in most cases in both groups on the admission day, however, lymphocyte levels dropped progressively and more severe lymphopenia occurred in IMV group. Increased amounts of plasma IL-6 and IL-10 were found in both groups on the admission day, the progressive decrease of which occurred in NIV cases rather than IMV cases, and the levels were higher in IMV cases during hospitalization.

Conclusions

Lymphocytopenia, neutrophilia, and increase of IL-6 and IL-10 occurred in SARS-CoV-2 infected patients in ICU, however, the dynamics of those were significantly different in IMV cases and NIV cases during hospitalization.
Deflating the RNA Mg2+bubble. Stereochemistry to the rescue!
Authors: Auffinger Pascal , Ennifar Eric , D’Ascenzo Luigi
Published: April 2020

Proper evaluation of the ionic structure of biomolecular systems remains challenging in X-ray and cryo-EM techniques but is essential for advancing our understanding of complex structure/activity/solvent relationships. However, numerous studies overestimate the number of Mg2+in the deposited structures and underrate the importance of stereochemical rules to correctly assign these ions. Herein, we re-evaluate the PDBid 6QNR and 6SJ6 models of the ribosome ionic structure and establish that stereochemical principles should always be considered when evaluating ion binding features, even when K+anomalous signals are available as it is the case for 6QNR. Assignment errors can result in misleading conceptions of the solvent structure of ribosomes and other RNA systems and should therefore be avoided. Our analysis resulted in a significant decrease of bound Mg2+ions in the 6QNR structure, suggesting that K+and not Mg2+is the prevalent ion in the ribosome 1stsolvation shell. We stress that the use of proper stereochemical guidelines is critical for deflating the current Mg2+bubble witnessed in many ribosome and other RNA structures. Herewith, we would like to draw the attention of the researchers interested in the ionic structure of biomolecular systems on the importance and complementarity of stereochemistry and other ion identification techniques such as those pertaining to the detection of anomalous signals of transition metals and K+. We also stress that for the identification of lighter ions such as Mg2+, Na+, …, stereochemistry coupled with high resolution structures remain the best currently available option.
Induction of long-lived potential aestivation states in laboratoryAn. gambiaemosquitoes
Authors: Krajacich Benjamin J. , Sullivan Margery , Faiman Roy , Veru Laura , Graber Leland , Lehmann Tovi
Published: April 2020

Background

HowAnophelinemosquitoes persist through the long dry season in Africa remains a gap in our understanding of these malaria vectors. To span this period in locations such as the Sahelian zone of Mali, mosquitoes must either migrate to areas of permanent water, recolonize areas as they again become favorable, or survive in harsh conditions including high temperatures, low humidity, and an absence of surface water (required for breeding). Adult mosquitoes surviving through this season must dramatically extend their typical lifespan (averaging 2-3 weeks) to 7 months. Previous work has found evidence that the malaria mosquitoAn. coluzzii, survives over 200 days in the wild between rainy seasons in a presumed state of aestivation (hibernation), but this state has so far not been replicated in laboratory conditions. The inability to recapitulate aestivation in the lab hinders addressing key questions such as how this state is induced, how it affects malaria vector competence, and its impact on disease transmission.

Methods

We compared survivorship of mosquitoes in climate-controlled incubators that adjusted humidity (40-85% RH), temperature (18-27 °C), and light conditions (8-12 hours of light). A range of conditions were chosen to mimic the late rainy and dry seasons as well as relevant extremes these mosquitoes may experience during aestivation.

Results

We found that by priming mosquitoes in conditions simulating the late wet season in Mali, and maintaining mosquitoes in reduced light/temperature, mean mosquito survival increased from 18.34 +/− 0.65 to 48.02 +/− 2.87 days, median survival increased from 19 (95% CI: 17-21) to 50 days (95% CI: 40-58), and the maximum longevity increased from 38 to 109 days (p-adj < 0.001). While this increase falls short of the 200+ day survival seen in field mosquitoes, this extension is substantially higher than previously found through environmental or dietary modulation and is hard to reconcile with states other than aestivation. Future work will expand on these findings, looking to further extend the gains in life span while also investigating transcriptional changes in genes affecting aging, metabolism, and epigenetic regulation; hormone and nutrient levels; and vector competence for malaria causing parasites.

Abstract Figure
Using coverage-based rarefaction to infer non-random species distributions
Authors: Engel Thore , Blowes Shane A. , McGlinn Daniel J. , May Felix , Gotelli Nicholas J. , McGill Brian J. , Chase Jonathan M.
Published: April 2020

Understanding how species are non-randomly distributed in space, as well as how the resulting spatial structure of diversity responds to ecological, biogeographic and anthropogenic drivers is a critical piece of the biodiversity puzzle. However, most metrics that quantify the spatial structure of diversity (i.e., community differentiation), such as Whittaker’s classical β-diversity metric are influenced by sampling effects. As a result, these measures are influenced by species pool size, species abundance distributions and numbers of individuals. Null models have been proposed to evaluate the degree of differentiation among communities due to spatial structuring relative to that expected from sampling effects. However, to date, these null models do not accommodate the influence of sample completeness (i.e. the proportion of the species pool in the sample). Here, we develop an approach that makes use of individual- and coverage-based rarefaction and extrapolation. Using spatially explicit simulations, we show that our derived metric,βC, captures changes in intraspecific aggregation independently of changes in the species pool size. We then provide two case studies examining spatial structure in forest plots spanning latitudinal gradients: (1) a re-analysis of the “Gentry” plot dataset, and (2) comparing a high diversity plot in Barro Colorado Island, Panama with a low diversity plot in Harvard Forest, Massachusetts, USA. We find no evidence for systematic changes in spatial structure with latitude in these datasets. As it is rooted in biodiversity sampling theory and explicitly controls for sample completeness, our approach represents an important advance over existing null models for spatial aggregation. Potential applications of the approach range from better descriptors of biogeographic diversity patterns to the consolidation of local and regional diversity trends in the current biodiversity crisis.

Open research statement

The novel code for the calculation ofβCcan be found in supplementary material S4. Empirical data sets utilized for this research are as follows: Phillips & Miller (2002), Orwig et al. (2015), Condit et al. (2019). Our research repository including the novel code is also available athttps://github.com/t-engel/betaCand will be uploaded to Zenodo upon acceptance of this manuscript.
Cold acclimation has a differential effect on leaf vascular bundle structure and carbon export rates in natural Arabidopsis accessions originating from southern and northern Europe
Authors: Schneider Katja , Abazaj Lorena , Niemann Cornelia , Schröder Laura , Nägele Thomas
Published: April 2020

Acclimation to low but non-freezing temperature represents an ecologically important process forArabidopsis thalianabut also for many other plant species from temperate regions. Cold acclimation comprises and affects numerous molecular and physiological processes and the maintenance of sugar supply of sink tissue by photosynthetically active source tissue is preliminary for plant survival. Here, we analysed the correlation of changes in vascular bundle structure at the leaf petiole and sucrose exudation rates before and after cold acclimation. We compared six natural Arabidopsis accessions originating from southern and northern Europe. Photosynthetic capacities, i.e. maximum and effective quantum yield of photosystem II, revealed a significant effect of condition but not of genotype. Only for northern accessions we observed a highly significant negative correlation between leaf sucrose exudation rates, xylem and petiole cross section areas. Further, only for northern accessions we observed a significant increase of vascular bundle and leaf petiole cross section area during cold acclimation. In contrast, variance of cross section areas of cold acclimated southern accessions was strongly reduced compared to control plants while mean areas remained similar under both conditions. In summary, our findings suggest that natural Arabidopsis accessions from northern Europe significantly adjust sink strength and leaf vascular bundle structure to stabilize plant growth and photosynthesis for survival under low and freezing temperature.
Single-cell transcriptomic profiling maps monocyte/macrophage transitions after myocardial infarction in mice
Authors: Rizzo Giuseppe , Vafadarnejad Ehsan , Arampatzi Panagiota , Silvestre Jean-Sébastien , Zernecke Alma , Saliba Antoine-Emmanuel , Cochain Clément
Published: April 2020

Rationale

Monocytes and macrophages have a critical and dual role in post-ischemic cardiac repair, as they can foster both tissue healing and damage. To decipher how monocytes/macrophages acquire heterogeneous functional phenotypes in the ischemic myocardium, we profiled the gene expression dynamics at the single-cell level in circulating and cardiac monocytes/macrophages following experimental myocardial infarction (MI) in mice.

Methods and results

Using time-series single-cell transcriptome and cell surface epitope analysis of blood and cardiac monocytes/macrophages, as well as the integration of publicly available and independently generated single-cell RNA-seq data, we tracked the transitions in circulating and cardiac monocyte/macrophage states from homeostatic conditions up to 11 days after MI in mice. We show that MI induces marked and rapid transitions in the cardiac mononuclear phagocyte population, with almost complete disappearance of tissue resident macrophages 1 day after ischemia, and rapid infiltration of monocytes that locally acquire discrete and time-dependent transcriptional states within 3 to 7 days. Ischemic injury induced a shift of circulating monocytes towards granulocyte-like transcriptional features (Chil3, Lcn2, Prtn3). Trajectory inference analysis indicated that while conversion to Ly6Clowmonocytes appears as the default fate of Ly6Chimonocytes in the blood, infiltrated monocytes acquired diverse gene expression signatures in the injured heart, notably transitioning to two main MI-associated macrophage populations characterized by MHCIIhiandTrem2hiIgf1higene expression signatures. Minor ischemia-associated macrophage populations with discrete gene expression signature suggesting specialized functions in e.g. iron handling or lipid metabolism were also observed. We further identified putative transcriptional regulators and new cell surface markers of cardiac monocyte/macrophage states.

Conclusions

Altogether, our work provides a comprehensive landscape of circulating and cardiac monocyte/macrophage states and their regulators after MI, and will help to further understand their contribution to post-myocardial infarction heart repair.
The global population of SARS-CoV-2 is composed of six major subtypes
Authors: Júnior Ivair José Morais , Polveiro Richard Costa , Souza Gabriel Medeiros , Bortolin Daniel Inserra , Sassaki Flávio Tetsuo , Lima Alison Talis Martins
Published: April 2020

The World Health Organization characterized the COVID-19 as a pandemic in March 2020, the second pandemic of the 21stcentury. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-stranded RNA betacoronavirus of the familyCoronaviridae. Expanding virus populations, as that of SARS-CoV-2, accumulate a number of narrowly shared polymorphisms imposing a confounding effect on traditional clustering methods. In this context, approaches that reduce the complexity of the sequence space occupied by the SARS-CoV-2 population are necessary for a robust clustering. Here, we proposed the subdivision of the global SARS-CoV-2 population into sixteen well-defined subtypes by focusing on the widely shared polymorphisms in nonstructural (nsp3,nsp4,nsp6,nsp12,nsp13 andnsp14) cistrons, structural (spikeandnucleocapsid) and accessory (ORF8) genes. Six virus subtypes were predominant in the population, but all sixteen showed amino acid replacements which might have phenotypic implications. We hypothesize that the virus subtypes detected in this study are records of the early stages of the SARS-CoV-2 diversification that were randomly sampled to compose the virus populations around the world, a typical founder effect. The genetic structure determined for the SARS-CoV-2 population provides substantial guidelines for maximizing the effectiveness of trials for testing the candidate vaccines or drugs.
Actin binding domain of Rng2 sparsely bound on F-actin strongly inhibits actin movement on myosin II
Authors: Hayakawa Yuuki , Takaine Masak , Ngo Kien Xuan , Imai Taiga , Yamada Masafumi D. , Behjat Arash Badami , Umeda Kenichi , Hirose Keiko , Yurtsever Ayhan , Kodera Noriyuki , Tokuraku Kiyotaka , Numata Osamu , Fukuma Takeshi , Ando Toshio , Nakano Kentaro , Uyeda Taro Q.P.
Published: April 2020

Substoichiometric binding of certain actin-binding proteins induces conformational changes in a disproportionally large number of actin protomers in actin filaments. Here, we report a case in which such conformational changes in actin filaments have profound functional consequences. Rng2 is an IQGAP protein implicated in the assembly and contraction of contractile rings inSchizosaccharomyces pombe. We found that the calponin-homology actin-binding domain of Rng2 (Rng2CHD) strongly inhibits the motility of actin filaments on myosin IIin vitro.On skeletal muscle myosin II-coated surfaces, Rng2CHD halved the sliding speed of actin filaments at a binding ratio of 1.3% (=1/77), and virtually stopped movement at a binding ratio of 11% (=1/9). Rng2CHD also inhibited actin movements onDictyosteliummyosin II, but in this case by inducing the detachment of actin filaments from myosin II-coated surfaces. Rng2CHD induced cooperative structural changes of actin filaments accompanied by shortening of the filament helical pitch, and reduced the affinity between actin filaments and subfragment 1 (S1) of muscle myosin II in the presence of ADP. Intriguingly, actin-activated ATPase of S1 was hardly inhibited by Rng2CHD. We suggest that sparsely bound Rng2CHD induces global structural changes of actin filaments and interferes with the force generation by actin-myosin II.
Single-nucleus transcriptomics reveals functional compartmentalization in syncytial skeletal muscle cells
Authors: Kim Minchul , Franke Vedran , Brandt Bettina , Lowenstein Elijah D. , Schöwel Verena , Spuler Simone , Akalin Altuna , Birchmeier Carmen
Published: April 2020

Syncytial skeletal muscle cells contain hundreds of nuclei in a shared cytoplasm. We investigated nuclear heterogeneity and transcriptional dynamics in the uninjured and regenerating muscle using single-nucleus RNA-sequencing (snRNAseq) of isolated nuclei from muscle fibers. This revealed distinct nuclear subtypes unrelated to fiber type diversity, completely novel subtypes as well as the expected ones at the neuromuscular and myotendinous junctions. In fibers of theMdxdystrophy mouse model, new subtypes emerged, among them nuclei expressing a repair signature that were also abundant in the muscle of dystrophy patients, and a nuclear population associated with necrotic fibers. Finally, modifications of our approach revealed the compartmentalization in the rare and specialized muscle spindle. Our data identifies new nuclear compartments of the myofiber and defines a molecular roadmap for their functional analyses; the data can be freely explored on the MyoExplorer server (https://shiny.mdc-berlin.net/MyoExplorer/).
Forget the stress: retrograde amnesia for the stress-induced impairment of extinction retrieval
Authors: Briggs James F. , McMullen Kaitlyn M.
Published: April 2020

We investigated whether cycloheximide (CHX) would induce amnesia for the stress-induced impairment of extinction retrieval. First, a single restraint stress session was demonstrated to impair extinction retrieval, but not fear conditioning. A second experiment showed that when CHX was administered immediately after restraint, rats exhibited significant extinction retrieval at test (i.e., retrograde amnesia for the stress). In a third experiment, the stress session impaired various amounts of extinction durations, suggesting that the stress inhibited extinction retrieval rather than enhancing the original fear learning. These results suggest memories for acute stress are susceptible to disruption, which could have clinical implications.
Learning-induced mRNA alterations in olfactory bulb mitral cells in neonatal rats
Authors: Nartey Michaelina N. , Peña-Castillo Lourdes , LeGrow Megan , Doré Jules , Bhattacharya Sriya , Darby-King Andrea , Carew Samantha J. , Yuan Qi , Harley Carolyn W. , McLean John H.
Published: April 2020

In the olfactory bulb, a cAMP/PKA/CREB-dependent form of learning occurs in the first week of life that provides a unique mammalian model for defining the epigenetic role of this evolutionarily ancient plasticity cascade. Odor preference learning in the week-old rat pup is rapidly induced by a 10-min pairing of odor and stroking. Memory is demonstrable at 24 h, but not 48 h, posttraining. Using this paradigm, pups that showed peppermint preference 30 min posttraining were sacrificed 20 min later for laser microdissection of odor-encoding mitral cells. Controls were given odor only. Microarray analysis revealed that 13 nonprotein-coding mRNAs linked to mRNA translation and splicing and 11 protein-coding mRNAs linked to transcription differed with odor preference training. MicroRNA23b, a translation inhibitor of multiple plasticity-related mRNAs, was down-regulated. Protein-coding transcription was up-regulated for Sec23b, Clic2, Rpp14, Dcbld1, Magee2, Mstn, Fam229b, RGD1566265, and Mgst2. Gng12 and Srcg1 mRNAs were down-regulated. Increases in Sec23b, Clic2, and Dcbld1 proteins were confirmed in mitral cells in situ at the same time point following training. The protein-coding changes are consistent with extracellular matrix remodeling and ryanodine receptor involvement in odor preference learning. A role for CREB and AP1 as triggers of memory-related mRNA regulation is supported. The small number of gene changes identified in the mitral cell input/output link for 24 h memory will facilitate investigation of the nature, and reversibility, of changes supporting temporally restricted long-term memory.
Crystal structures of two furazidin polymorphs revealed by a joint effort of crystal structure prediction and NMR crystallography
Authors: Dudek Marta K. , Paluch Piotr , Pindelska Edyta
Published: April 2020

This work presents the crystal structure determination of two elusive polymorphs of furazidin, an antibacterial agent, employing a combination of crystal structure prediction (CSP) calculations and an NMR crystallography approach. Two previously uncharacterized neat crystal forms, one of which has two symmetry-independent molecules (form I), whereas the other one is a Z′ = 1 polymorph (form II), crystallize in P21/c and P
1 space groups, respectively, and both are built by different conformers, displaying different intermolecular interactions. It is demonstrated that the usage of either CSP or NMR crystallography alone is insufficient to successfully elucidate the above-mentioned crystal structures, especially in the case of the Z′ = 2 polymorph. In addition, cases of serendipitous agreement in terms of 1H or 13C NMR data obtained for the CSP-generated crystal structures different from the ones observed in the laboratory (false-positive matches) are analyzed and described. While for the majority of analyzed crystal structures the obtained agreement with the NMR experiment is indicative of some structural features in common with the experimental structure, the mentioned serendipity observed in exceptional cases points to the necessity of caution when using an NMR crystallography approach in crystal structure determination.
Crystal and solution structures of fragments of the human leucocyte common antigen-related protein
Authors: Vilstrup Joachim , Simonsen Amanda , Birkefeldt Thea , Strandbygård Dorthe , Lyngsø Jeppe , Pedersen Jan Skov , Thirup Søren
Published: April 2020

Leucocyte common antigen-related protein (LAR) is a post-synaptic type I transmembrane receptor protein that is important for neuronal functionality and is genetically coupled to neuronal disorders such as attention deficit hyperactivity disorder (ADHD). To understand the molecular function of LAR, structural and biochemical studies of protein fragments derived from the ectodomain of human LAR have been performed. The crystal structure of a fragment encompassing the first four FNIII domains (LARFN1–4) showed a characteristic L shape. SAXS data suggested limited flexibility within LARFN1–4, while rigid-body refinement of the SAXS data using the X-ray-derived atomic model showed a smaller angle between the domains defining the L shape compared with the crystal structure. The capabilities of the individual LAR fragments to interact with heparin was examined using microscale thermophoresis and heparin-affinity chromatography. The results showed that the three N-terminal immunoglobulin domains (LARIg1–3) and the four C-terminal FNIII domains (LARFN5–8) both bound heparin, while LARFN1–4 did not. The low-molecular-weight heparin drug Innohep induced a shift in hydrodynamic volume as assessed by size-exclusion chromatography of LARIg1–3 and LARFN5–8, while the chemically defined pentameric heparin drug Arixtra did not. Together, the presented results suggest the presence of an additional heparin-binding site in human LAR.