bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sphingosine‐1‐Phosphate Receptor 1 Mediated Vasodilation in Human Arterioles
Authors: Katunaric Boran , Schulz Mary E. , Freed Julie K. 
Published: April 2020

Precise regulation of vascular resistance is critical to maintain proper tissue perfusion. Recent data in animal models have shown that sphingolipids, a ubiquitous class of bioactive lipid messengers, can influence vasomotor tone via dilation or constriction. It has been suggested that sphingosine‐1‐phosphate (S1P) elicits vasodilation through generation of endothelial cell nitric oxide (NO) via activation of sphingosine‐1‐phosphate receptor 1 (S1PR1). We therefore examined the hypothesis that S1P is a regulator of human microvascular tone and elicits dilation via S1PR1‐induced increase in NO. Arterioles from healthy human adipose tissue were dissected and prepared for videomicroscopy, equilibrated and pre‐constricted with endothelin 1. Changes in arteriolar luminal diameter were recorded in response to increasing concentrations of S1P (10−12 to 10−6M) in the presence or absence of the S1PR1 receptor antagonist W146 (10−5M), nitric oxide synthase (NOS) inhibitor Nω‐nitro‐
l‐arginine (L‐NAME, 10−4M) or hydrogen peroxide (H2O2) scavenger polyethylene glycol‐catalase (peg‐Cat, 500U/ml). Administration of exogenous S1P induced vasodilation in healthy vessels to a maximal dilation of 63.7%±5.0, n=8 (mean±SEM). As with previous animal studies, vascular constriction was observed with higher, but still physiological levels of S1P (10−6 M). Vasodilation due to S1P was reduced following inhibition of S1PR1 compared to S1P alone (1.8%±4, n=5). In the presence of L‐NAME, S1P‐induced dilation decreased (9%±7.9, n=6). Interestingly, addition of peg‐Cat, an H2O2 scavenger, also decreased S1P‐induced dilation (11.1%±6.6, n=3). Together these data suggest that S1PR1 is a critical mechanistic component of S1P‐induced vasodilation in the human vasculature. Further, the S1P vasodilatory pathway may require formation of H2O2 in addition to NO.Support or Funding InformationThis research was supported by National Institute of Health (NHLBI) K08 HL141562‐02 (JKF)
Bioengineered microRNAs suppress lung cancer cell metabolism and proliferation through targeting of folate cycle
Authors: Chen Yixin , Liu Zhenzhen , Tu Meijuan , Batra Neelu , Yu Ai-ming 
Published: April 2020

Lung cancer remains as the leading cause of cancer deaths in the world. Ver recently, we have established a novel technology for the production of bioengineered miRNA agents for the study of cancer biology and new therapies. Using recombinant miRNA molecules produced and folded in living cells, we identified a number of the most effective miRNAs for the inhibition of non‐small cell lung cancer (NSCLC) cell proliferation, among which miR‐22‐3p, miR‐9‐5p and miR‐218‐5p are all predicted to interfere with folate cycle and one‐carbon metabolism. The serine hydroxymethyltransferase‐1 (SHMT‐1), a tumor biomarker and important enzyme in folate biotransformation, was verified as a new target for both miR‐9‐5p and miR‐218‐5p. The methylenetetrahydrofolate dehydrogenase 1 like (MTHFD1L) was proven to be regulated by miR‐9‐5p directly. Furthermore, both methylenetetrahydrofolate reductase (MTHFR) and methylenetetrahydrofolate dehydrogenase‐2 (MTHFD2) were significantly suppressed by miR‐22‐3p in NSCLC cells. As determined by accurate LC‐MS/MS methods, folate metabolites and amino acid metabolome were altered remarkably by individual miRNAs in human NSCLC cells. Consequently, glycolysis rate and mitochondrial function were significantly inhibited in NSCLC cells treated with these miRNAs, accompanied by cell cycle arrest, ROS accumulation, NADP+/NADPH imbalance and other metabolic dysfunctions. In conclusion, our results demonstrated that bioengineered miR‐22‐3p, miR‐9‐5p, and miR‐218‐5p act on folate cycle to suppress NSCLC cell metabolic capacity and exhibit strong antiproliferation activities. These findings provide new insights into mechanistic actions of tumor suppressive miRNAs and development of novel therapeutic strategies.Support or Funding InformationThis study was supported by National Cancer Institute (grant No. R01CA225958) and National Institute of General Medical Sciences (R01GM113888), National Institutes of Health.
Highly effective methods for expression/purification of recombinant human HSP90 and its four distinct (N‐LR‐M‐C) domains
Authors: Thongboonkerd Visith , Aluksanasuwan Siripat , Plumworasawat Sirikanya , Manissorn Juthatip , Peerapen Paleerath 
Published: April 2020

Heat shock protein 90 (HSP90) plays essential roles in normal physiology to maintain homeostasis and in many human diseases. It comprises four distinct domains, including NH2‐terminal (N), charged linker region (LR), middle (M), and COOH‐terminal (C) domains, all of which are important for regulating HSP90 biological functions. We reported herein detailed protocols to produce recombinant full‐length (FL) and all these four domains of human HSP90 from Escherichia coli. cDNAs encoding FL, N, LR, M and C domains of human HSP90α were amplified and cloned into pET‐32b(+) expression vector. All HSP90 constructs were expressed as soluble Trx‐His‐S tagged proteins after induction with 0.25 mM isopropyl‐β‐D‐thiogalactopyranoside (IPTG) at 18°C overnight and further purified by affinity chromatography using nickel‐nitrilotriacetic acid (Ni‐NTA) resin. The enterokinase (EK) digestion was optimized for efficient cleavage of the Trx‐His‐S tag from each HSP90 construct by varying concentrations of EK (0.5–1 U) and urea (0–3 M). After rebinding to Ni‐NTA resin, each HSP90 construct was highly purified and approximately 0.1–1 mg proteins were obtained from 100 ml of bacterial culture. All the purified HSP90 constructs were successfully confirmed by tandem mass spectrometry (nanoLC‐ESI‐ETD MS/MS). Our expression and purification protocols would facilitate further structural and functional studies of human HSP90.Support or Funding InformationThis study was supported by Mahidol University research grant and the Thailand Research Fund (IRN60W0004).
Use of Ion Exchange and Lectin Chromatograpy To Fractionate Proteins from Carcinus maenus
Authors: Johnson Heidi , Myracle Angela D. , Grant Jennifer E. 
Published: April 2020

Across many different species of crabs, it is notable that their shells have a high abundance of protein. For instance, the snow crab is 34.2% w/w of protein within its shell (Asunchion, et al., 2011.) And while the blue crab contains about 33.4% w/w protein within its shell (Lee et al 2017), the red crab contains about 16% w/w protein (Aklog 2016). Less is known about the European green crab, Carcinus maenus, which is a species found in Europe and North Africa. This organism has also invaded the coast of Maine.We have developed an acid extraction and acetone precipitation strategy for isolating proteins from the shells of the European green crab, Carcinus maenus. Typically, roughly 5 to 10 proteins are visible when this extract is analyzed by 12% SDS‐PAGE gel. In this study, cation and anion‐exchange resins, and lectin resins, were utilized to fractionate protein species based on their charge and glycoprotein content, respectively. This work reports on the progress of these studies.This work is of value to the study of bioactive materials present in shelled marine organisms.
Membraneless Organelles and Viscosity Changes during Desiccation: A New Phase in Anhydrobiosis
Authors: Belott Clinton J. , Janis Brett R. , Sithu Tryphena S. , Menze Michael A. 
Published: April 2020

AfrLEA6 is an intrinsically disordered protein found in the anhydrobiotic cysts of Artemia franciscana. AfrLEA6 shares homology with plant seed maturation proteins (SMPs), which have been linked to the longevity of orthodox seeds in the desiccated state. Therefore, it was hypothesized that ectopically expressing AfrLEA6 will increase the desiccation tolerance of a desiccation‐sensitive Drosophila melanogaster (Kc167) cell line. Surprisingly, ectopically expressed AfrLEA6 was found to undergo a liquid‐liquid phase separation (LLPS) in the cytoplasm of Kc167 cells. The overall architecture of the protein is composed of two SMP domains connected with a glycine‐ and proline‐rich spacer to a potential protein‐binding domain. It was determined that AfrLEA6 LLPS is dependent on the SMP domains, regulated by polysome assembly and disassembly, and may best be described as a specialized biphasic stress granule. It is speculated that AfrLEA6 stress granules protect desiccation‐sensitive proteins prior to glassy‐state formation during water loss. This hypothesis was strengthened by the observation that expression of AfrLEA6 in Kc167 cells increases their desiccation tolerance. Unexpectedly, AfrLEA6 also increases intracellular viscosity during desiccation compared to control cells, which reduced plasma membrane fusion between adjacent cells and may protect against internal sheer stresses. These data agree with recently reported cellular dielectrophoretic data, that AfrLEA6 expressed in Kc167 cells underwent a shift to become more entangled when cells were exposed to osmotic stress, thereby suggesting an increase intracellular viscosity. In A. franciscana, a rapid increase in cytoplasmic viscosity at relatively high‐water contents may be key to successfully entering the anhydrobiotic state, while trehalose glass formation at relatively low‐water contents may create a more stable intracellular environment for long‐term dormancy.Support or Funding InformationSupported by NSF IOS‐1659970.
Ivermectin as a potential COVID-19 treatment from the pharmacokinetic point of view: antiviral levels are not likely attainable with known dosing regimens
Authors: Momekov Georgi , Momekova Denitsa 
Published: April 2020

AbstractThe broad-spectrum antiparasitic agent ivermectin has been very recently found to inhibit SARS-CoV-2 in vitro and proposed as a candidate for drug repurposing in COVID-19. In the present report the in vitro antiviral activity end-points are analyzed from the pharmacokinetic perspective. The available pharmacokinetic data from clinically relevant and excessive dosing studies indicate that the SARS-CoV-2 inhibitory concentrations are not likely to be attainable in humans.
Estimates of regional infectivity of COVID-19 in the United Kingdom following imposition of social distancing measures
Authors: Challen Robert , Tsaneva-Atanasova Krasimira , Pitt Martin , Edwards Tom , Gompels Luke , Lacasa Lucas , Brooks-Pollock Ellen , Martin Chris , Griffith Gareth , Danon Leon 
Published: April 2020

AbstractWe describe regional variation in the reproduction number of SARS-CoV-2 infections observed using publicly reported data in the UK, with a view to understanding both if there are clear hot spots in viral spread in the country, or other spatial patterns. Based on case data up to the 9th April, we estimate that the viral replication number remains above 1 overall in the UK but that its trend is to decrease. This suggests the peak of the first wave of COVID-19 patients is imminent. We find that there is significant regional variation in the UK and that this is changing over time. Within England currently the reproductive ratio is lowest in the Midlands (1.11 95% CI 1.07; 1.14), and highest in the North East of England (1.38 95% CI 1.33-1.42). There are long and variable time delays between infection and detection of cases, and thus it remains unclear whether the reduction in the reproductive number is a result of social distancing measures. If we are to prevent further outbreaks, it is critical that we both reduce the time taken for detection and improve our ability to predict the regional spread of outbreaks.
Comparison of psychological distress and demand induced by COVID-19 during the lockdown period in patients undergoing peritoneal dialysis and hemodialysis: a cross-section study in a tertiary hospital
Authors: Xia Xiaoxiao , Wu Xiaofang , Zhou Xueli , Zang Zhiyun , Pu Li , Li Zi 
Published: April 2020

ABSTRACTBackgroundSince the outbreak of COVID-19 in December 2019, it has spread rapidly and widely, bringing great psychological pressure to the public. In order to prevent the epidemic, lockdown was required in many areas of China, which led to inconvenience of treatment for dialysis patients. To explore the psychological distress and the psychological demand induced by COVID-19 in the patients undergoing dialysis and compare the difference between hemodialysis (HD) and peritoneal (PD) patients during the lockdown period.MethodsQuestionnaires were given to the dialysis patients in West China Hospital of Sichuan University. The Impact of Event Scale (IES) was used to investigate the patients’ trauma-related distress in response to COVID-19.Results232 eligible respondents were enrolled in this cross-section study, consisting of 156 PD patients and 76 HD patients. The median IES score for all the enrolled patients was 8.00 (2.00-19.00), which belonged to the subclinical dimension of post-traumatic stress symptoms. HD patients had a significant higher IES score than PD patients (11.50 vs 8.00) (p<0.05). HD patients already got more psychological support from the medical staff. There was no significant difference on further demand of psychological support between the two groups. In the multivariate regression analysis, we found that dialysis vintage, the impact of COVID-19 on the severity of illness and daily life, and confidence in overcoming the disease contributed to IES score (p<0.05).ConclusionsHD patients had more severe trauma-related stress symptoms than PD patients. When major public healthy events occurred, careful psychological estimate and sufficient psychological support should be provided to the dialysis patients, especially to the HD patients.
SimCOVID: Open-Source Simulation Programs for the COVID-19 Outbreak
Authors: Abdulrahman Ismael 
Published: April 2020

AbstractThis paper presents open-source computer simulation programs developed for simulating, tracking, and estimating the COVID-19 outbreak. The programs consist of two separate parts: one set of programs built in Simulink with a block diagram display, and another one coded in MATLAB as scripts. The mathematical model used in this package is the SIR, SEIR, and SEIRD models represented by a set of differential-algebraic equations. It can be easily modified to develop new models for the problem. A generalized method is adopted to simulate worldwide outbreaks in an efficient, fast, and simple way. To get a good tracking of the virus spread, a sum of sigmoid functions was proposed to capture any dynamic changes in the data. The parameters used for the input (infection and recovery rate functions) are computed using the parameter estimation tool in MATLAB. Several statistic methods were applied for the rate function including linear, mean, root-mean-square, and standard deviation. In addition, an adaptive neuro-fuzzy inference system is employed and proposed to train the model and predict its output. The programs can be used as a teaching tool and for research studies.
“Knowledge and practices towards COVID-19 during its outbreak: a multinational cross-sectional study”
Authors: Naser Abdallah Y , Dahmash Eman Zmaily , Alwafi Hassan , Alsairafi Zahra Khalil , Rajeh Ahmed M. Al , Alhartani Yosra J , Turkistani Fawaz Mohammad , Alyami Hamad S. 
Published: April 2020

ABSTRACTBackgroundThe emergence of COVID-19 globally coupled with its unknown aetiology and its high transmission rate has created an unprecedented state of emergency worldwide. Public knowledge and awareness about COVID-19 are essential in suppressing its pandemic status.MethodA cross-sectional study using an online survey was conducted between 19th of March and 6th of April 2020 in three Middle Eastern countries (Jordan, Saudi Arabia and Kuwait) to explore the knowledge and practices of Middle Eastern population towards COVID-19. A previously developed questionnaire was used. Multiple linear regression analysis was used to identify predictors of COVID-19 knowledge.ResultsA total of 1,208 participants were involved in this study from the three countries (Jordan = 389, Saudi Arabia = 433, and Kuwait = 386). The majority of participants (n = 810, 67.2%) were females and aged 30 to 49 years (n = 501, 41.5%). Participants had moderate overall COVID-19 knowledge with a mean score of 7.93 (±1.72) out of 12, 66.1%. Participants had better knowledge about disease prevention and control with 83.0%, whereas the lowest sub-scale scores were for questions about disease transmission routes (43.3%). High education level was an important predictor of greater COVID-19 knowledge scores (p<0.01).ConclusionMiddle Eastern participants are of a relatively low level of knowledge about COVID-19, particularly regarding its transmission routes. Policymakers are recommended to develop informative COVID-19 related campaigns targeted specifically towards university students, unemployed individuals and those with lower levels of education.
Estimating the impact of mobility patterns on COVID-19 infection rates in 11 European countries
Authors: Bryant Patrick , Elofsson Arne 
Published: April 2020

BackgroundAs governments across Europe have issued non-pharmaceutical interventions (NPIs) such as social distancing and school closing, the mobility patterns in these countries have changed. It is likely different countries and populations respond differently to the same NPIs and that these differences are reflected in the epidemic development.MethodsWe build a Bayesian model that estimates the number of deaths on a given day dependent on changes in the basic reproductive number, R0, due to changes in mobility patterns. We utilize mobility data from Google mobility reports using five different categories: retail and recreation, grocery and pharmacy, transit stations, workplace and residential. The importance of each mobility category for predicting changes in R0is estimated through the model.FindingsThe changes in mobility have a large overlap with the introduction of governmental NPIs, highlighting the importance of government action for population behavioural change. The grocery and pharmacy sector is estimated to account for 97 % of the reduction in R0(95% confidence interval [0·79,0·99]).InterpretationOur model predicts three-week epidemic forecasts, using real-time observations of changes in mobility patterns, which can provide governments with direct feedback on the effects of their NPIs. The model predicts the changes in a majority of the countries accurately but overestimates the impact of NPIs in Sweden and Denmark and underestimates them in France and Belgium.FundingFinancial support: Swedish Research Council for Natural Science, grant No. VR-2016-06301 and Swedish E-science Research Center. Computational resources: Swedish National Infrastructure for Computing, grant No. SNIC-2019/3-319.
Severe underestimation of COVID-19 case numbers: effect of epidemic growth rate and test restrictions
Authors: Richterich Peter 
Published: April 2020

AbstractTo understand the scope and development of the COVID-19 pandemic, knowledge of the number of infected persons is essential. Often, the number of “confirmed cases”, which is based on positive RT-PCR test results, is regarded as a reasonable indicator. However, limited COVID-19 test capacities in many countries are restricting the amount of testing that can be done. This can lead to the implementation of testing policies that restrict access to COVID-19 tests, and to testing backlogs and delays. As a result, confirmed case numbers can be significantly lower than the actual number of infections, especially during rapid growth phases of the epidemic.This study examines the quantitative relation between infections and reported confirmed case numbers for two different testing strategies, “limited” and “inclusive” testing, in relation to the growth rate of the epidemic. The results indicate that confirmed case numbers understate the actual number of infections substantially; during rapid growth phases where the daily growth rate can reach or exceed 30%, as has been seen in many countries, the confirmed case numbers under-report actual infections by up to 50 to 100-fold.
Estimating the number of SARS-CoV-2 infections in the United States
Authors: Thorpe Dayton G. , Lyberger Kelsey 
Published: April 2020

AbstractWe apply a model developed by The COVID-19 Response Team [S. Flaxman, S. Mishra, A. Gandy, et al., “Estimating the number of infections and the impact of non-pharmaceutical interventions on COVID-19 in 11 European countries,” tech. rep., Imperial College London, 2020.] to estimate the total number of SARS-CoV-2 infections in the United States. Across the United States we estimate as of April 18, 2020 the fraction of the population infected was 4.6% [3.6%, 5.8%], 21 times the portion of the population with a positive test result. Excluding New York state, which we estimate accounts for over half of infections in the United States, we estimate an infection rate of 2.3% [2.1%, 2.8%].We include the timing of each state’s implementation of interventions including encouraging social distancing, closing schools, banning public events, and a lockdown / stay-at-home order. We assume fatalities are reported correctly and infer the number and timing of infections based on the infection fatality rate measured in populations that were tested universally for SARS-CoV-2. Underreporting of deaths would drive our estimates to be too low. Reporting of deaths on the wrong day could drive errors in either direction. This model does not include effects of herd immunity; in states where the estimated infection rate is very high - namely, New York - our estimates may be too high.
Carbon Stock of Human-Disturbed Forest Areas in Bukidnon, Philippines
Authors: Medina Michael Arieh P. , Cabahug Vember C. , Zapico Gabriel Erico G. 
Published: April 2020

AbstractA carbon stock assessment was done on two forest areas in Bukidnon, Philippines specifically in Mt. Kiamo in Kibalabag Village and Mt. Capistrano in Managok Village both in Malaybalay City, Bukidnon. Using a nested sampling design, tree diameter at breast height as well as tree height were measured. Allometric equations were then used to calculate for the above and below ground biomass density of trees. Destructive sampling was then employed to determine the biomass density of understory and litterfall, while composite sampling was done for soil analysis. Carbon content was then used to compute for the carbon stock of the different carbon pools in the studied ecosystems. The average biomass density of the two areas was found to be 247.80 Mg ha−1which are closely similar to other areas of the same forest type in Mindanao. Likewise the average carbon stock of the two areas is 143.14 MgC ha−1which is similar to tree plantations based on previous studies. Furthermore, the said carbon stock is approximately 40% lower than the country average for natural forests (250 MgC ha−1). The results demonstrate the extent of the diminishing carbon sequestration capability of forest areas due to human disturbance.