bluuebunny/crossref_metadata_2025 huggingface dataset:
Slip-Fall Predictors in Community-Dwelling, Ambulatory Stroke Survivors: A Cross-sectional Study
Authors: Gangwani Rachana , Dusane Shamali , Wang Shuaijie , Kannan Lakshmi , Wang Edward , Fung Joyce , Bhatt Tanvi
Published: August 2020

Background and Purpose:

Considering the multifactorial nature and the often-grave consequences of falls in people with chronic stroke (PwCS), determining measurements that best predict fall risk is essential for identifying those who are at high risk. We aimed to determine measures from the domains of the International Classification of Functioning, Disability and Health (ICF) that can predict laboratory-induced slip-related fall risk among PwCS.

Methods:

Fifty-six PwCS participated in the experiment in which they were subjected to an unannounced slip of the paretic leg while walking on an overground walkway. Prior to the slip, they were given a battery of tests to assess fall risk factors. Balance was assessed using performance-based tests and instrumented measures. Other fall risk factors assessed were severity of sensorimotor impairment, muscle strength, physical activity level, and psychosocial factors. Logistic regression analysis was performed for all variables. The accuracy of each measure was examined based on its sensitivity and specificity for fall risk prediction.

Results:

Of the 56 participants, 24 (43%) fell upon slipping while 32 (57%) recovered their balance. The multivariate logistic regression analysis model identified dynamic gait stability, hip extensor strength, and the Timed Up and Go (TUG) score as significant laboratory-induced slip-fall predictors with a combined sensitivity of 75%, a specificity of 79.2%, and an overall accuracy of 77.3%.

Discussion and Conclusions:

The results indicate that fall risk measures within the ICF domains—body, structure, and function (dynamic gait stability and hip extensor strength) and activity limitation (TUG)—could provide a sensitive laboratory-induced slip-fall prediction model in PwCS.

Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A323).
Does Pregnenolone Adjunct to Risperidone Ameliorate Irritable Behavior in Adolescents With Autism Spectrum Disorder: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial?
Authors: Ayatollahi Arghavan , Bagheri Sayna , Ashraf-Ganjouei Amir , Moradi Kamyar , Mohammadi Mohammad-Reza , Akhondzadeh Shahin
Published: August 2020

Objectives

Pregnenolone is a neurosteroid with modulatory effects on γ-aminobutyric acid neurotransmission. Here, we aimed to evaluate the effectiveness and safety of pregnenolone add-on to risperidone in adolescents with autism spectrum disorders (ASD).

Methods

Sixty-four ASD patients were randomly allocated to receive either pregnenolone (n = 32) or matching placebo (n = 32) in addition to risperidone. The Aberrant Behavior Checklist-Community Edition scale was used to evaluate the behavioral status of patients at baseline, week 5, and the trial end point. The change in score of irritability subscale was the primary outcome. Frequency of adverse effects due to trial medications was compared between the treatment groups.

Results

Fifty-nine patients completed the trial (30 in pregnenolone and 29 in the placebo arm). Baseline characteristics of both treatment groups were similar (P > 0.05). Repeated measures analysis was suggestive of greater exhibited improvement for the pregnenolone group on irritability, stereotypy, and hyperactivity subscales of the Aberrant Behavior Checklist-Community Edition over the trial period (F = 3.84, df = 1.96, P = 0.025; F = 4.29, df = 1.39, P = 0.029; F = 6.55, df = 1.67, P = 0.004, respectively). Nonetheless, the alterations in lethargy and inappropriate speech domains scores were similar for both arms (F = 0.93, df = 1.49, P = 0.375; F = 1.10, df = 1.60, P = 0.325, respectively). There was no significant difference in frequency as well as severity of adverse effects between the 2 groups.

Conclusions

Pregnenolone adjunct to risperidone could attenuate core features associated with ASD.
Mitogen- and stress-activated protein kinase-1 activation is involved in melanocortin-induced BDNF expression in Neuro2a neuronal cells
Authors: Zhang Weibo , Wu Yue
Published: August 2020

Melanocortins are neuropeptides exerting versatile functions in the nervous system. Melanocortin 4 receptor (MC4R) is primarily expressed in the brain and is thought to be a major mediator for melanocortin. Brain-derived neurotrophic factor (BDNF) may be a crucial downstream molecule of MC4R activation, to yield neurite outgrowth, neuroregenerative, anorexigenic and other actions. In this study, we stimulated Neuro2a murine neuronal cells with an α-melanocyte stimulating hormone (α-MSH) analog, [Nle(4), D-Phe(7)]melanocyte-stimulating hormone (NDP-MSH). In Neuro2a cells, NDP-MSH promoted neurite outgrowth. Upon NDP-MSH administration, BDNF expression was greatly enhanced. Furthermore, this effect was effectively reversed by the MC4R antagonist, JKC-363. We found that NDP-MSH treatment activated the ERK cascade and its downstream kinase MSK1 (mitogen- and stress-activated protein kinase-1). Antagonism of the MSK1 cascade by a specific inhibitor or overexpression of a defective MSK1 mutant interrupted the phosphorylation of the transcription factor cAMP-response element binding protein (CREB), blocking BDNF upregulation. In addition, MSK1 activation triggered an epigenetic alteration in histone H3 (Ser10), facilitating the expression of the BDNF gene. Taken together, our results showed that MSK1 kinase positively activates MC4R-induced BDNF expression via modulating the phosphorylation of CREB and histone H3 in Neuro2a neuronal cells.
Interaction network effects on position- and velocity-based models of collective motion
Authors: Turgut Ali Emre , Boz İhsan Caner , Okay İlkin Ege , Ferrante Eliseo , Huepe Cristián
Published: August 2020

We study how the structure of the interaction network affects self-organized collective motion in two minimal models of self-propelled agents: the Vicsek model and the Active-Elastic (AE) model. We perform simulations with topologies that interpolate between a nearest-neighbour network and random networks with different degree distributions to analyse the relationship between the interaction topology and the resilience to noise of the ordered state. For the Vicsek case, we find that a higher fraction of random connections with homogeneous or power-law degree distribution increases the critical noise, and thus the resilience to noise, as expected due to small-world effects. Surprisingly, for the AE model, a higher fraction of random links with power-law degree distribution can decrease this resilience, despite most links being long-range. We explain this effect through a simple mechanical analogy, arguing that the larger presence of agents with few connections contributes localized low-energy modes that are easily excited by noise, thus hindering the collective dynamics. These results demonstrate the strong effects of the interaction topology on self-organization. Our work suggests potential roles of the interaction network structure in biological collective behaviour and could also help improve decentralized swarm robotics control and other distributed consensus systems.
Estimating the protective effect of case isolation with transmission tree reconstruction during the Ebola outbreak in Nigeria, 2014
Authors: Chan Yat Hin , Nishiura Hiroshi
Published: August 2020

The mainstream interventions used during the 2014–2016 Ebola epidemic were contact tracing and case isolation. The Ebola outbreak in Nigeria that formed part of the 2014–2016 epidemic demonstrated the effectiveness of control interventions with a 100% hospitalization rate. Here, we aim to explicitly estimate the protective effect of case isolation, reconstructing the time events of onset of illness and hospitalization as well as the transmission network. We show that case isolation reduced the reproduction number and shortened the serial interval. Employing Bayesian inference with the Markov chain Monte Carlo method for parameter estimation and assuming that the reproduction number exponentially declines over time, the protective effect of case isolation was estimated to be 39.7% (95% credible interval: 2.4%–82.1%). The individual protective effect of case isolation was also estimated, showing that the effectiveness was dependent on the speed, i.e. the time from onset of illness to hospitalization.
A mathematical analysis for constructal design of tree flow networks under unsteady flow
Authors: Soni Bharat , Miguel Antonio F. , Kumar Nayak Ameeya
Published: August 2020

Tree flow networks play an important role in both natural and man-made systems. In an effort to develop a deeper understanding of the optimal design of these networks, we have developed a simple analytical approach to deal with steady and unsteady flows. As a result, optimal relations for the homothetic ratio of tube sizes and optimal angles between daughter tubes are obtained. The obtained optimum homothetic ratios satisfy the criterion of the minimization procedure of flow impedance based on geometry and the svelteness ratio. The robustness, accuracy and convergence of model are also proved mathematically in order to validate the results.
Performance of a new molecular assay for the detection of gastrointestinal pathogens
Authors: Gingras Bruce A. , Maggiore Jack A.
Published: August 2020

Introduction. Conventional diagnostic laboratory algorithms for determining the cause of infectious gastroenteritis include culture, biochemical identification and immunoassays. In addition, multiplex PCR-based testing has advanced into the gastroenterology diagnostic arena in recent years.

Aim. The purpose of this study was to evaluate the performance of a new molecular test (Diagnostics Solutions Laboratory GI-MAP) for the detection of bacterial and parasitic pathogens in stool samples spiked with known organisms.

Methodology. Faeces from a healthy human subject were pooled into a standard matrix and screened for the absence of bacteria, parasites and

Helicobacter pylori

antigen. Once confirmed negative single faecal aliquots from the matrix were spiked with solely one pathogen-type from a panel of 14 bacterial pathogens or one of 2 parasitic pathogens at a density of 5×106 organisms ml−1. Sixteen spiked samples in appropriate transport media were sent to two testing labs, specifically a reference site using the PCR-based BioFire FilmArray Gastrointestinal Panel, and a second lab using the GI-MAP assay. Seven negative control samples comprised solely of stool matrix were also submitted.

Results. Significant variability was found when the GI-MAP assay was used to test normal stool matrix with and without known bacteria and parasites at densities well within the expected limits of detection. The GI-MAP assay displayed a sensitivity of 80 % and a specificity of only 26 % due to many false positive results. This assay also reported quantitative numbers for pathogens. The BioFire FilmArray Gastrointestinal Panel achieved a sensitivity and specificity of 100 %.

Conclusion. The highly variable results for the GI-MAP assay were unexpected due to the precise pre-spike analysis and the overall maturation of nucleic acid amplification methods within the industry. Problematic to this assay is the poor level of specificity displayed by this assay reporting the presence of several pathogens, which could cause clinicians to treat with antibacterial and/or antiparasitic agents in the absence of any true pathogens.
Rhodovarius crocodyli sp. nov., isolated from a crocodile pond
Authors: Chen Wen-Ming , Xie Yi-Ru , Sheu Der-Shyan , Tsai Jyh-Ming , Sheu Shih-Yi
Published: August 2020

Bacterial strain CCP-6T, isolated from a freshwater pond in Taiwan, was characterized using a polyphasic taxonomy approach. Phylogenetic analyses based on 16S rRNA gene sequences and an up-to-date bacterial core gene set (92 protein clusters) indicated that strain CCP-6Tis affiliated with species in the genusRhodovarius. Strain CCP-6Twas most closely related toRhodovarius lipocyclicusCCUG 44693Twith a 98.9% 16S rRNA gene sequence similarity. Cells were Gram-stain-negative, aerobic, non-motile, rod-shaped and formed light pink-coloured colonies. Optimal growth occurred at 30 °C, pH 6 and in the absence of NaCl. The major fatty acids of strain CCP-6Twere C18 : 1ω7c, C16 : 0and C19 : 0cycloω8c. The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, phosphatidyldimethylethanolamine, phosphatidylmethylethanolamine, diphosphatidylglycerol, three unidentified aminophospholipids and an unidentified phospholipid. The predominant polyamine was spermidine. The major isoprenoid quinone was Q-10. The DNA G+C content of the genomic DNA was 69.3 mol%. Strain CCP-6Tshowed 85.8% average nucleotide identity and 14.5% digital DNA–DNA hybridization identity withRhodovarius lipocyclicusCCUG 44693T. On the basis of the genotypic, chemotaxonomic and phenotypic data, strain CCP-6Trepresents a novel species in the genusRhodovarius, for which the nameRhodovarius crocodylisp. nov. is proposed. The type strain is CCP-6T(=BCRC 81095T=LMG 30310T=KCTC 62188T).
High frequency of colonization by diverse clones of beta-lactam-resistant Gram-negative bacilli in haemodialysis: different sources of transmission outside the renal unit?
Authors: Vanegas Johanna M. , Salazar-Ospina Lorena , Montoya-Urrego Daniela , Builes Julián , Roncancio Gustavo E. , Jiménez J. Natalia
Published: August 2020

Introduction. While colonization by

Staphylococcus aureus

in haemodialysis patients has been assessed, knowledge about colonization by beta-lactam-resistant Gram-negative bacilli is still limited.

Aim. To describe clinical and molecular characteristics in haemodialysis patients colonized by

S. aureus

(MSSA-MRSA) and beta-lactam-resistant Gram-negative bacilli in an ambulatory renal unit.

Methodology. The study included patients with central venous catheters in an outpatient haemodialysis facility in Medellín, Colombia (October 2017–October 2018). Swab specimens were collected from the nostrils and skin around vascular access to assess colonization by

S. aureus

(MSSA-MRSA). Stool samples were collected from each patient to evaluate beta-lactam-resistant Gram-negative bacilli colonization. Molecular typing included PFGE, multilocus sequence typing (MLST), spa typing and enterobacterial repetitive intergenic consensus-PCR (ERIC). Clinical information was obtained from medical records and personal interview.

Results. A total of 210 patients were included in the study.

S. aureus

colonization was observed in 33.8 % (n=71) of the patients, 4.8 % (n=10) of which were colonized by methicillin-resistant

S. aureus

. Stool samples were collected from 165 patients and of these 41.2 % (n=68) and 11.5 % (n=19) were colonized by extended-spectrum-beta-lactamase-producing (ESBL) and carbapenem-resistant bacilli, respectively. Typing methods revealed high genetic diversity among

S. aureus

and ESBL-producing Gram-negative bacilli (ESBL-GNB). Antibiotic use and hospitalization in the previous 6 months were observed in more than half of the studied population.

Conclusion. The high colonization by ESBL-GNB in haemodialysis patients shows evidence for the need for stronger surveillance, not only for

S. aureus

but also for multidrug-resistant bacilli in order to avoid their spread. Additionally, the high genetic diversity suggests other sources of transmission outside the renal unit instead of horizontal transmission between patients.
Heart disease mortality during the early pandemic period in the United States
Authors: Faust Jeremy Samuel , Lin Zhenqiu , Wright Kalen N. , Di Iorio Michael A. , Walsh Carrie D. , Krumholz Harlan M.
Published: August 2020

Importance

The coronavirus disease 2019 (COVID-19) outbreak has been associated with decreases in acute myocardial infarction diagnoses (AMI) and admissions in the United States. Whether this affected heart disease deaths is unknown.

Objective

To determine whether changes in heart disease deaths occurred during the early pandemic period in the US, we analyzed areas without large COVID-19 outbreaks. This isolated the effect of decreased healthcare-seeking behavior during the early outbreak.

Design, Setting, and Participants

We performed an observational study of heart disease-specific mortality using National Center for Health Statistics data (NCHS). Weekly provisional counts were disaggregated by jurisdiction of occurrence during 2019 and 2020 for all-cause deaths, COVID-19 deaths, and heart disease deaths. For the primary analysis, jurisdictions were included if; 1) There was no all-cause excess mortality during the early pandemic period (weeks 14–17, 2020); 2) The completeness of that data was estimated by NCHS to be >97% as of July 22, 2020, and; 3) Decreases in emergency department (ED) visits occurred during the study period. We compared heart disease death rates during the early pandemic period with corresponding weeks in 2019 and a pre-pandemic control period of 2020 as a sensitivity analysis. Incident rate and rate ratios were calculated.

Exposure

The US COVID-19 outbreak.

Main Outcomes and Measures

Incidence of heart disease deaths.

Results

Twelve states met the primary inclusion criteria, capturing 747,375,188 person-weeks for the early pandemic period and 740,987,984 person-weeks for the 2019 control period. The mean incidence rate (per 100,000 person-weeks) for heart disease in states without excess deaths during the early pandemic period was 3.95 (95% CI 3.83 to 4.06) versus 4.19 (95% CI 4.14 to 4.23) during the corresponding period in 2019. The incident rate ratio (2020/2019) was 0.91 (95% CI 0.87 to 0.97). No state recorded an increase from either the corresponding period in 2019 or the 2020 prepandemic control period. Two states recorded fewer heart disease deaths.

Conclusions and Relevance

This observational study found a decrease in heart disease deaths during the early US outbreak in regions without significant COVID-19 burdens, despite decreases in ED utilization. Long term follow-up data are needed.
Multi-organ Proteomic Landscape of COVID-19 Autopsies
Authors: Nie Xiu , Qian Liujia , Sun Rui , Huang Bo , Dong Xiaochuan , Xiao Qi , Zhang Qiushi , Lu Tian , Yue Liang , Chen Shuo , Li Xiang , Sun Yaoting , Li Lu , Xu Luang , Li Yan , Yang Ming , Xue Zhangzhi , Liang Shuang , Ding Xuan , Yuan Chunhui , Peng Li , Liu Wei , Yi Xiao , Lyu Mengge , Xiao Guixiang , Xu Xia , Ge Weigang , He Jiale , Fan Jun , Wu Junhua , Luo Meng , Chang Xiaona , Pan Huaxiong , Cai Xue , Zhou Junjie , Yu Jing , Gao Huanhuan , Xie Mingxing , Wang Sihua , Ruan Guan , Chen Hao , Su Hua , Mei Heng , Luo Danju , Zhao Dashi , Xu Fei , Li Yan , Zhu Yi , Xia Jiahong , Hu Yu , Guo Tiannan
Published: August 2020

The molecular pathology of multi-organ injuries in COVID-19 patients remains unclear, preventing effective therapeutics development. Here, we report an in-depth multi-organ proteomic landscape of COVID-19 patient autopsy samples. By integrative analysis of proteomes of seven organs, namely lung, spleen, liver, heart, kidney, thyroid and testis, we characterized 11,394 proteins, in which 5336 were perturbed in COVID-19 patients compared to controls. Our data showed that CTSL, rather than ACE2, was significantly upregulated in the lung from COVID-19 patients. Dysregulation of protein translation, glucose metabolism, fatty acid metabolism was detected in multiple organs. Our data suggested upon SARS-CoV-2 infection, hyperinflammation might be triggered which in turn induces damage of gas exchange barrier in the lung, leading to hypoxia, angiogenesis, coagulation and fibrosis in the lung, kidney, spleen, liver, heart and thyroid. Evidence for testicular injuries included reduced Leydig cells, suppressed cholesterol biosynthesis and sperm mobility. In summary, this study depicts the multi-organ proteomic landscape of COVID-19 autopsies, and uncovered dysregulated proteins and biological processes, offering novel therapeutic clues.

HIGHLIGHTS

Characterization of 5336 regulated proteins out of 11,394 quantified proteins in the lung, spleen, liver, kidney, heart, thyroid and testis autopsies from 19 patients died from COVID-19.

CTSL, rather than ACE2, was significantly upregulated in the lung from COVID-19 patients.

Evidence for suppression of glucose metabolism in the spleen, liver and kidney; suppression of fatty acid metabolism in the kidney; enhanced fatty acid metabolism in the lung, spleen, liver, heart and thyroid from COVID-19 patients; enhanced protein translation initiation in the lung, liver, renal medulla and thyroid.

Tentative model for multi-organ injuries in patients died from COVID-19: SARS-CoV-2 infection triggers hyperinflammatory which in turn induces damage of gas exchange barrier in the lung, leading to hypoxia, angiogenesis, coagulation and fibrosis in the lung, kidney, spleen, liver, heart, kidney and thyroid.

Testicular injuries in COVID-19 patients included reduced Leydig cells, suppressed cholesterol biosynthesis and sperm mobility.
How are residents trained in neuropathology? A survey of neurology program directors in the United States
Authors: Rayi Appaji , Rajneesh Kiran , Punia Vineet , Start Amanda R.
Published: August 2020

To understand the current state of neuropathology education during neurology residency training in the United States, we electronically distributed a 16-item survey to 150 adult and 70 child neurology program directors (PDs). The survey inquired about their residency program characteristics, neuropathology curriculum and assessment methods, trainee performance in the subject and attitude about neuropathology education. Descriptive analysis was used to summarize categorical variables as frequencies and percentages and continuous as means and standard deviations. We conducted a series of Mann-Whitney U and Fisher’s exact tests to evaluate differences between various program characteristics. Sixty-four (29%) PDs responded to the survey, including 45 (30%) adult and 19 (27%) child neurology PDs. Thirty-one programs required a dedicated neuropathology rotation typically during the latter years of the program. Residency in-service training exam (RITE) was the main assessment tool (92%) for assessing the trainee’s knowledge in neuropathology. Overall, 87% of the PDs agreed that neuropathology is essential and 85% agreed that there is a clear need for a defined neuropathology curriculum during residency training. There was no difference in the RITE scores between programs with and without a dedicated neuropathology rotation. We conclude that a neuropathology rotation was felt to be essential even though the RITE scores did not differ between programs with and without a dedicated rotation. Alternative evaluation methods and neuropathology training techniques such as web modules, virtual reality may be helpful tools to optimize training and need consideration.
Effects of case- and population-based COVID-19 interventions in Taiwan
Authors: Ng Ta-Chou , Cheng Hao-Yuan , Chang Hsiao-Han , Liu Cheng-Chieh , Yang Chih-Chi , Jian Shu-Wan , Liu Ding-Ping , Cohen Ted , Lin Hsien-Ho
Published: August 2020

In the first wave of the COVID-19 pandemic, broad usage of non-pharmaceutical interventions played a crucial role in controlling epidemics1–6. However, the substantial economic and societal costs of continuous use of border controls, travel restrictions, and physical distancing measures suggest that these measures may not be sustainable and that policymakers have to seek strategies to lift the restrictions. Taiwan was one of the few countries that demonstrated initial success in eliminating the COVID-19 outbreak without strict lockdown or school closure. To understand the key contributors to the successful control, we applied a stochastic branching model to empirical case data to evaluate and compare the effectiveness of more targeted case-based (including contact tracing and quarantine) and less targeted population-based interventions (including social distancing and face mask use) in Taiwan. We found that case-based interventions alone would not be sufficient to contain the epidemic, even in a setting where a highly efficient contact tracing program was in place. The voluntary population-based interventions have reduced the reproduction numbers by more than 60% and have likely played a critical role at the early stage of the outbreak. Our analysis of Taiwan’s success highlights that coordinated efforts from both the government and the citizens are indispensable in the fight against COVID-19 pandemic.
Practice of Hyperglycaemia Control in Intensive Care Units of the Military Hospital, Sudan – Needs of a Protocol
Authors: El-Raheem Ghada Omer Hamad Abd , Abdallah Mudawi Mohammed Ahmed , Noma Mounkaila
Published: August 2020

Hyperglycaemia is a major risk factor in critically ill patients as it leads to adverse outcomes and mortality in diabetic and non-diabetic patients. The target blood glucose remained controversial; this study aimed to contribute in assessing the practice of hyperglycaemia control in intensive care units of Khartoum Military Hospital. Furthermore, it proposed a protocol for hyperglycaemia control based on findings. A hospital-based cross-sectional study assessed the awareness and practice towards hyperglycaemia management in a sample of 83 healthcare staff selected through stratified random sampling technique. In addition, 55 patients were enrolled, through quota sampling, after excluding those with diabetic ketoacidosis, hyperosmolar-hyperglycaemic state and patients < 18 years. A self-administrated questionnaire enabled to collect data from healthcare staff, patients data were extracted from medical records. SPSS 23 was used to analyse the collected data. Chi-square and ANOVA tests assessed the association among variables. All statistical tests were considered statistically significant whenp< 0.05. The training on hyperglycaemia control differed statistically (p= 0.017) among healthcare staff. The target glycaemic level (140-180 mg/dl) was knew by 11.1% of the study participants. Neither the knowledge nor the practice of hyperglycaemia control methods differed among staff (p> 0.05). The use of sliding scale was 79.3% across the ICUs with a statistically significant difference (p= 0.002). 31.5% of patients had received glycaemic control based on different methods and 11.8% were in the targeted blood glucose level. Sliding scale was the prevalent method used by doctors (71.4%) and nurses (81.6%). A patient benefited from insulin infusion method, which achieved the NICE-SUGAR target. The poor knowledge and lack of awareness towards hyperglycaemia monitoring led to inappropriate implementation of glycaemia control methods across the Military Hospital ICUs. Sustained training programs on hyperglycaemia control to ICU staff and the availability of a protocol on glycaemia control are highly required.
Non-apoptotic function of caspase-3 in morphogenesis of epithelial tubes ofDrosophilarenal system
Authors: Ojha Shainy , Tapadia Madhu G.
Published: August 2020

Cells trigger apoptosis to eliminate themselves from the system, when tissue needs to be sculptured or they detect any abnormality within them, thus preventing irreparable damage to the host.DrosophilaMalpighian tubules express apoptotic proteins, without succumbing to cell death. Here we present evidence to show apoptosis independent role of executioner caspase, Drice, for precise architecture and function of Malpighian tubules. Drice is required for precise cytoskeleton organization and convergent extension, failing which the morphology, size, cellular number and arrangement gets affected. Acquisition of star shape of stellate cells in adult Malpighian tubules requires Drice. We demonstrate that Drice regulates expression of Rho1GTPase and localization of polarity proteins. Our study shows a probable mechanism by which Drice governs tubulogenesis via Rho1GTPase mediated coordinated organization of actin cytoskeleton and membrane stablisation. Furthermore, defective morphology of tubules leads to abnormal osmoregulation and excretory functions. Collectively our findings suggest a possible non-apoptotic function of caspase-3 in the fine tuning of cell mobility during tubule development and our results will add to the growing understanding of diverse roles of caspases during its evolution in metazoans.
Bacterial modification of the host glycosaminoglycan heparan sulfate modulates SARS-CoV-2 infectivity
Authors: Martino Cameron , Kellman Benjamin P. , Sandoval Daniel R. , Clausen Thomas Mandel , Marotz Clarisse A. , Song Se Jin , Wandro Stephen , Zaramela Livia S. , Salido Benítez Rodolfo Antonio , Zhu Qiyun , Armingol Erick , Vázquez-Baeza Yoshiki , McDonald Daniel , Sorrentino James T. , Taylor Bryn , Belda-Ferre Pedro , Liang Chenguang , Zhang Yujie , Schifanella Luca , Klatt Nichole R. , Havulinna Aki S. , Jousilahti Pekka , Huang Shi , Haiminen Niina , Parida Laxmi , Kim Ho-Cheol , Swafford Austin D. , Zengler Karsten , Cheng Susan , Inouye Michael , Niiranen Teemu , Jain Mohit , Salomaa Veikko , Esko Jeffrey D. , Lewis Nathan E. , Knight Rob
Published: August 2020

The human microbiota has a close relationship with human disease and it remodels components of the glycocalyx including heparan sulfate (HS). Studies of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) spike protein receptor binding domain suggest that infection requires binding to HS and angiotensin converting enzyme 2 (ACE2) in a codependent manner. Here, we show that commensal host bacterial communities can modify HS and thereby modulate SARS-CoV-2 spike protein binding and that these communities change with host age and sex. Common human-associated commensal bacteria whose genomes encode HS-modifying enzymes were identified. The prevalence of these bacteria and the expression of key microbial glycosidases in bronchoalveolar lavage fluid (BALF) was lower in adult COVID-19 patients than in healthy controls. The presence of HS-modifying bacteria decreased with age in two large survey datasets, FINRISK 2002 and American Gut, revealing one possible mechanism for the observed increase in COVID-19 susceptibility with age.In vitro, bacterial glycosidases from unpurified culture media supernatants fully blocked SARS-CoV-2 spike binding to human H1299 protein lung adenocarcinoma cells. HS-modifying bacteria in human microbial communities may regulate viral adhesion, and loss of these commensals could predispose individuals to infection. Understanding the impact of shifts in microbial community composition and bacterial lyases on SARS-CoV-2 infection may lead to new therapeutics and diagnosis of susceptibility.

Graphical Abstract. Diagram of hypothesis for bacterial mediation of SARS-CoV-2 infection through heparan sulfate (HS).

It is well known that host microbes groom the mucosa where they reside. Recent investigations have shown that HS, a major component of mucosal layers, is necessary for SARS-CoV-2 infection. In this study we examine the impact of microbial modification of HS on viral attachment.
Hypoxia triggers collective aerotactic migration inDictyostelium discoideum
Authors: Cochet-Escartin O. , Demircigil M. , Hirose S. , Allais B. , Gonzalo P. , Mikaelian I. , Funamoto K. , Anjard C. , Calvez V. , Rieu J.-P.
Published: August 2020

It is well known that eukaryotic cells can sense oxygen (O2) and adapt their metabolism accordingly. It is less known that they can also move towards regions of higher oxygen level (aerotaxis). Using a self-generated hypoxic assay, we show that the social amoebaDictyostelium discoideumdisplays a spectacular aerotactic behavior. When a cell colony is covered by a coverglass, cells quickly consume the available O2and the ones close to the periphery move directionally outward forming a dense ring keeping a constant speed and density. To confirm that O2is the main molecular player in this seemingly collective process, we combined two technological developments, porphyrin based O2sensing films and microfluidic O2gradient generators. We showed thatDictyosteliumcells exhibit aerotactic and aerokinetic (increased speed at low O2) response in an extremely low range of O2concentration (0-1.5%) indicative of a very efficient detection mechanism. The various cell behaviors under self-generated or imposed O2gradients were modeled with a very satisfactory quantitative agreement using anin silicocellular Potts model built on experimental observations. This computational model was complemented with a parsimonious ‘Go or Grow’ partial differential equation (PDE) model. In both models, we found that the collective migration of a dense ring can be explained by the interplay between cell division and the modulation of aerotaxis, without the need for cell-cell communication.
Host auxin machinery is important in mediating root architecture changes induced byPseudomonas fluorescensGM30 andSerendipita indica
Authors: Matthiadis Anna , Sukumar Poornima , DeLeon Alyssa , Pelletier Dale , Labbé Jessy L. , Tuskan Gerald A , Kalluri Udaya C
Published: August 2020

Auxin is a key phytohormone that is integral to plant developmental processes including those underlying root initiation, elongation, and branching. Beneficial microbes have been shown to have an impact on root development, potentially mediated through auxin. In this study, we explore the role of host auxin signaling and transport components in mediating the root growth promoting effects of beneficial microbes. Towards this end, we undertook co-culture studies ofArabidopsis thalianaplants with microbes previously reported to promote lateral root proliferation and produce auxin. Two types of beneficial microbes were included in the present study; a plant growth promoting bacterial species of interest,Pseudomonas fluorescensGM30, and a well-studied plant growth promoting fungal species,Serendipita indica (Piriformospora indica). Following co-culture, lateral root production was found restored in auxin transport inhibitor-treated plants, suggesting involvement of microbe and/or microbially-produced auxin in altering plant auxin levels. In order to clarify the role of host auxin signaling and transport pathways in mediating interactions with bacterial and fungal species, we employed a suite of auxin genetic mutants as hosts in co-culture screens. Our result show that the transport proteins PIN2, PIN3, and PIN7 and the signaling protein ARF19, are required for mediating root architecture effects by the bacterial and/or fungal species. Mutants corresponding to these proteins did not significantly respond to co-culture treatment and did not show increases in lateral root production and lateral root density. These results implicate the importance of host auxin signaling in both bacterial and fungal induced changes in root architecture and serve as a driver for future research on understanding the role of auxin-dependent and auxin-independent pathways in mediating plant-microbe interactions in economically important crop species.
Normothermic Ex-vivo Kidney Perfusion in a Porcine Auto-Transplantation Model Preserves the Expression of Key Mitochondrial Proteins: An Unbiased Proteomics Analysis
Authors: McEvoy Caitriona M. , Clotet-Freixas Sergi , Tokar Tomas , Pastrello Chiara , Reid Shelby , Batruch Ihor , RaoPeters Adrien A.E. , Kaths J. Moritz , Urbanellis Peter , Farkona Sofia , Van Julie A.D. , Urquhart Bradley L. , John Rohan , Jurisica Igor , Robinson Lisa A. , Selzner Markus , Konvalinka Ana
Published: August 2020

Normothermicex-vivokidney perfusion (NEVKP) results in significantly improved graft function in porcine auto-transplant models of DCD injury compared to static cold storage (SCS); however, the molecular mechanisms underlying these beneficial effects remain unclear. We performed an unbiased proteomics analysis of 28 kidney biopsies obtained at 3 time points from pig kidneys subjected to 30-minutes of warm ischemia, followed by 8 hours of NEVKP or SCS, and auto-transplantation. 70/6593 proteins quantified were differentially expressed between NEVKP and SCS groups (FDR<0.05). Proteins increased in NEVKP mediated key metabolic processes including fatty acid ß-oxidation, the TCA-cycle and oxidative phosphorylation. Comparison of our findings with external datasets of ischemia-reperfusion, and other models of kidney injury confirmed that 47 of our proteins represent a common signature of kidney injury reversed or attenuated by NEVKP. We validated key metabolic proteins (ETFB, CPT2) by immunoblotting. Transcription factor databases identified PPARGC1A, PPARA/G/D and RXRA/B as the upstream regulators of our dataset, and we confirmed their increased expression in NEVKP with RT-PCR. The proteome-level changes observed in NEVKP mediate critical metabolic pathways that may explain the improved graft function observed. These effects may be coordinated by PPAR-family transcription factors, and may represent novel therapeutic targets in ischemia-reperfusion injury.
Generalized linear models provide a measure of virulence for specific mutations in SARS-CoV-2 strains
Authors: Oulas Anastasis , Zanti Maria , Tomazou Marios , Zachariou Margarita , Minadakis George , Bourdakou Marilena M , Pavlidis Pavlos , Spyrou George M.
Published: August 2020

This study aims to highlight SARS-COV-2 mutations which are associated with increased or decreased viral virulence. We utilize, genetic data from all strains available from GISAID and countries’ regional information such as deaths and cases per million as well as covid-19-related public health austerity measure response times. Initial indications of selective advantage of specific mutations can be obtained from calculating their frequencies across viral strains. By applying modelling approaches, we provide additional information that is not evident from standard statistics or mutation frequencies alone. We therefore, propose a more precise way of selecting informative mutations. We highlight two interesting mutations found in genes N (P13L) and ORF3a (Q57H). The former appears to be significantly associated with decreased deaths and cases per million according to our models, while the latter shows an opposing association with decreased deaths and increased cases per million. Moreover, protein structure prediction tools show that the mutations infer conformational changes to the protein that significantly alter its structure when compared to the reference protein.
Sodium leak channel as a therapeutic target for neuronal sensitization in neuropathic pain
Authors: Zhang Donghang , Zhao Wenling , Liu Jin , Ou Mengchan , Liang Peng , Li Jia , Chen Yali , Liao Daqing , Bai Siqi , Shen Jiefei , Chen Xiangdong , Huang Han , Zhou Cheng
Published: August 2020

Neuropathic pain affects up to 10% of the total population and no specific target is ideal for therapeutic need. The sodium leak channel (NALCN), a voltage-independent cation channel, mediates the background Na+leak conductance and controls neuronal excitability and rhythmic behaviors. Here, we show that increases of NALCN expression and function in dorsal root ganglion (DRG) and dorsal spinal cord contribute to chronic constriction injury (CCI)-induced neuropathic pain in rodents. NALCN current and neuronal excitability in acutely isolated DRG neurons and spinal cord slices of rats were increased after CCI which were decreased to normal levels by NALCN-siRNA. Accordingly, pain-related symptoms were significantly alleviated by NALCN-siRNA-mediated NALCN knockdown and completely reversed by NALCN-shRNA-mediated NALCN knockdown in rats or by conditional NALCN knockout in mice. Our results indicate that increases in NALCN expression and function contribute to CCI-induced neuronal sensitization; therefore, NALCN may be a novel therapeutic target for neuropathic pain.
Oxidative Stress Responses and Nutrient Starvation in MCHM TreatedSaccharomyces cerevisiae
Authors: Ayers Michael C. , Sherman Zachary N. , Gallagher Jennifer E.G.
Published: August 2020

In 2014, the coal cleaning chemical 4-methylcyclohexane methanol (MCHM) spilled into the water supply for 300,000 West Virginians. Initial toxicology tests showed relatively mild results, but the underlying effects on cellular biology were underexplored. Treated wildtype yeast cells grew poorly, but there was only a small decrease in cell viability. Cell cycle analysis revealed an absence of cells in S phase within thirty minutes of treatment. Cells accumulated in G1 over a six-hour time course, indicating arrest instead of death. A genetic screen of the haploid knockout collection revealed 329 high confidence genes required for optimal growth in MCHM. These genes encode three major cell processes: mitochondrial gene expression/translation, the vacuolar ATPase, and aromatic amino acid biosynthesis. The transcriptome showed an upregulation of pleiotropic drug response genes and amino acid biosynthetic genes and downregulation in ribosome biosynthesis. Analysis of these datasets pointed to environmental stress response activation upon treatment. Overlap in datasets included the aromatic amino acid genesARO1,ARO3, and four of the fiveTRPgenes. This implicated nutrient deprivation as the signal for stress response. Excess supplementation of nutrients and amino acids did not improve growth on MCHM, so the source of nutrient deprivation signal is still unclear. Reactive oxygen species and DNA damage were directly detected with MCHM treatment, but timepoints showed these accumulated slower than cells arrested. We propose that wildtype cells arrest from nutrient deprivation and survive, accumulating oxidative damage through the implementation of robust environmental stress responses.
Casein Kinase 1G2 Suppresses Necroptosis-Promoted Testis Aging by Inhibiting Receptor-Interacting Kinase 3
Authors: Li Dianrong , Ai Youwei , Guo Jia , Dong Baijun , Li Lin , Cai Gaihong , Chen She , Xu Dan , Wang Fengchao , Wang Xiaodong
Published: August 2020

Casein kinases are a large family of intracellular serine/threonine kinases that control a variety of cellular signaling functions. Here we report that a member of casein kinase 1 family, casein kinase 1G2, CSNK1G2, binds and inhibits the activation of receptor-interacting kinase 3, RIP3, thereby attenuating RIP3-mediated necroptosis. The binding of CSNK1G2 to RIP3 is triggered by auto-phosphorylation at serine 211/threonine 215 sites in its C-terminal domain. CSNK1G2-knockout mice showed significantly enhanced necroptosis response and pre-maturing aging of their testis, a phenotype that was rescued by either double knockout of the RIP3 gene or feeding the animal with a RIP1 kinase inhibitor-containing diet. Moreover, CSNK1G2 is also co-expressed with RIP3 in human testis, and the necroptosis activation marker phospho-MLKL was observed in the testis of old (>80) but not young men, indicating that the testis-aging program carried out by the RIP3-mediated and CSNK1G2-attenuated necroptosis is evolutionarily conserved between mice and men.
Structure of long-range direct and indirect spinocerebellar pathways as well as local spinal circuits mediating proprioception
Authors: Pop Iliodora V. , Espinosa Felipe , Blevins Cheasequah J. , Okafor Portia C. , Ogujiofor Osita W. , Goyal Megan , Mona Bishakha , Landy Mark A. , Dean Kevin M. , Gurumurthy Channabasavaiah B. , Lai Helen C.
Published: August 2020

Proprioception, the sense of limb and body position, generates a map of the body that is essential for proper motor control, yet we know little about precisely how neurons in proprioceptive pathways are wired. Defining the anatomy of secondary neurons in the spinal cord that integrate and relay proprioceptive and potentially cutaneous information from the periphery to the cerebellum is fundamental to understanding how proprioceptive circuits function. Here, we use genetic tools in both male and female mice to define the unique anatomical trajectories of long-range direct and indirect spinocerebellar pathways as well as local intersegmental spinal circuits. We find that Clarke’s column (CC) neurons, a major contributor to the direct spinocerebellar pathway, has mossy fiber terminals that diversify extensively in the cerebellar cortex with axons terminating bilaterally, but with no significant axon collaterals within the spinal cord, medulla, or cerebellar nuclei. By contrast, we find that two of the indirect pathways, the spino-lateral reticular nucleus (spino-LRt) and spino-olivary pathways, are in part, derived from cervicalAtoh1-lineage neurons, while thoracolumbarAtoh1-lineage neurons project mostly locally within the spinal cord. Notably, while cervical and thoracolumbarAtoh1-lineage neurons connect locally with motor neurons, no CC to motor neuron connections were detected. Silencing of caudalAtoh1- lineage neurons results in a subtle motor impairment consistent with a defect in local proprioceptive circuitry. Altogether, we define anatomical differences between long-range direct, indirect, and local proprioceptive subcircuits that likely mediate different components of proprioceptive-motor behaviors.

Significance Statement

We define the anatomy of long-range direct and indirect spinocerebellar pathways as well as local spinal proprioceptive circuits. We observe that mossy fiber axon terminals of Clarke’s column (CC) neurons diversify proprioceptive information across granule cells in multiple lobules on both ipsilateral and contralateral sides sending no significant collaterals within the spinal cord, medulla, or cerebellar nuclei. Strikingly, we find that cervical spinal cordAtoh1-lineage neurons form mainly the indirect spino- lateral reticular nucleus and spino-olivary tracts and thoracolumbarAtoh1-lineage neurons project locally within the spinal cord while only a fewAtoh1-lineage neurons form a direct spinocerebellar tract. Altogether, we define the development, anatomical projections, and some behavioral consequences of silencing spinal proprioceptive pathways.
Seeding of outbreaks of COVID-19 by contaminated fresh and frozen food
Authors: Fisher Dale , Reilly Alan , Kang Eng Zheng Adrian , Cook Alex , Anderson Danielle
Published: August 2020

The authors have withdrawn this manuscript because some aspects of the published work were completed prior to regulatory approval. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.