bluuebunny/crossref_metadata_2025 huggingface dataset:
Sleep and diurnal rest-activity rhythm disturbances in a mouse model of Alzheimer’s disease
Authors: Filon Mikolaj J , Wallace Eli , Wright Samantha , Douglas Dylan J , Steinberg Lauren I , Verkuilen Carissa L , Westmark Pamela R , Maganti Rama K , Westmark Cara J
Published: May 2020

Study Objectives

Accumulating evidence suggests a strong association between sleep, amyloid-beta (Aβ) deposition, and Alzheimer’s disease (AD). We sought to determine if (1) deficits in rest-activity rhythms and sleep are significant phenotypes in J20 AD mice, (2) metabotropic glutamate receptor 5 inhibitors (mGluR5) could rescue deficits in rest-activity rhythms and sleep, and (3) Aβ levels are responsive to treatment with mGluR5 inhibitors.

Methods

Diurnal rest-activity levels were measured by actigraphy and sleep-wake patterns by electroencephalography, while animals were chronically treated with mGluR5 inhibitors. Behavioral tests were performed, and Aβ levels measured in brain lysates.

Results

J20 mice exhibited a 4.5-h delay in the acrophase of activity levels compared to wild-type littermates and spent less time in rapid eye movement (REM) sleep during the second half of the light period. J20 mice also exhibited decreased non-rapid eye movement (NREM) delta power but increased NREM sigma power. The mGluR5 inhibitor CTEP rescued the REM sleep deficit and improved NREM delta and sigma power but did not correct rest-activity rhythms. No statistically significant differences were observed in Aβ levels, rotarod performance, or the passive avoidance task following chronic mGluR5 inhibitor treatment.

Conclusions

J20 mice have disruptions in rest-activity rhythms and reduced homeostatic sleep pressure (reduced NREM delta power). NREM delta power was increased following treatment with a mGluR5 inhibitor. Drug bioavailability was poor. Further work is necessary to determine if mGluR5 is a viable target for treating sleep phenotypes in AD.
Characterization of Peptacetobacter hominis gen. nov., sp. nov., isolated from human faeces, and proposal for the reclassification of Clostridium hiranonis within the genus Peptacetobacter
Authors: Chen Xiao-Jiao , Wang Zhan-Qiang , Zhou Zu-Yi , Zeng Nian-Yi , Huang Qing-Fa , Wang Zhong-Wei , Tang Wen-Li , Zhou Hong-Wei
Published: May 2020

A novel, Gram-stain-positive, rod-shaped, non-motile, non-spore-forming, obligately anaerobic bacterium, designated strain ZHW00191T, was isolated from human faeces and characterized by using a polyphasic taxonomic approach. Growth occurred at 25–45 °C (optimum, 37–42 °C), at pH 5.5–10.0 (optimum, pH 6.5–7.0) and with 0–2 % (w/v) NaCl (optimum, 0 %). The end products of glucose fermentation were acetic acid, isobutyric acid and isovaleric acid and a small amount of propionic acid. The dominant cellular fatty acids (>10 %) of strain ZHW00191Twere C16 : 0, C18 : 1ω9сand C18 : 2ω6,9с. Its polar lipid profile comprised diphosphatidylglycerol, phosphatidylglycerol, three unidentified phospholipids and ten unidentified glycolipids. Respiratory quinones were not detected. The cell-wall peptidoglycan containedmeso-2,6-diaminopimelic acid, and the whole-cell sugars were ribose and glucose. The genomic DNA G+C content was 32.8 mol%. Analysis of the 16S rRNA gene sequence indicated that ZHW00191Twas most closely related toClostridium hiranonisTO-931T(95.3 % similarity). Average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) analyses with closely related reference strains indicated that reassociation values were both well below the thresholds of 95–96% and 70 % for species delineation, respectively. Based on phenotypic, chemotaxonomic and genetic studies, a novel genus,Peptacetobactergen. nov., is proposed. The novel isolate ZHW00191T(=JCM 33482T=GDMCC 1.1530T) is proposed as the type strain of the type speciesPeptacetobacter hominisgen. nov., sp. nov. of the proposed new genus. Furthermore, it is proposed thatClostridium hiranonisbe transferred to this novel genus, asPeptacetobacter hiranoniscomb. nov.
Luteimonas gilva sp. nov., isolated from farmland soil
Authors: Xiong Luo , An Lijin , Zong Yuanyuan , Wang Mengjie , Wang Gejiao , Li Mingshun
Published: May 2020

A Gram-stain-negative, rod-shaped bacterium, strain H23T, was isolated from farmland soil sampled in Enshi City, Hubei Province, PR China. The isolate grew optimally at 28–32 °C, pH 8.0 and with 0.5 % (w/v) NaCl. Based on the results of 16S rRNA gene sequence and phylogenetic analyses, strain H23T belonged to the genus

Luteimonas

with the highest degree of 16S rRNA gene sequence similarity to

Luteimonas cucumeris

Y4T (97.41 %). The DNA G+C content was 65.88 mol%. The average nucleotide identity and the Genome-to-Genome Distance Calculator results also showed low relatedness (below 95 and 70 %, respectively) between strain H23T and type strains in the genus

Luteimonas

. Ubiquinone-8 was the predominant quinone. The major fatty acids were iso-C15 : 0, iso-C16 : 0, iso-C17 : 0 and iso-C17 : 1 ω9c. Polar lipids were dominated by diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and unidentified phospholipids. Low digital DNA–DNA hybridization values, as well as physiological and biochemical differences, such as no casein hydrolysis, being catalase-negative, and tesing positive for cystine arylamidase, α-chymotrypsin and N-acetyl-β-glucosaminidase, could distinguish strain H23T from its closely related species. Strain H23T is considered to represent a novel species in the genus

Luteimonas

, for which the name Luteimonas gilva sp. nov. is proposed, with strain H23T (=CCTCC AB 2019255T=KCTC 72593T) as the type strain.
Pusillimonas maritima sp. nov., isolated from surface seawater
Authors: Li Jianyang , Qi Mingming , Lai Qiliang , Dong Chunming , Liu Xiupian , Wang Guangyi , Shao Zongze
Published: May 2020

Two Gram-stain-negative, short rod-shaped and non-flagellated strains, designated 17-4AT and L52-1-41, were isolated from the surface seawater of the Indian Ocean and South China Sea, respectively. The 16S rRNA genes of the two strains shared sequence similarity of 99.45 %. Strain 17-4AT shared the highest 16S rRNA gene similarity of 98.02 % with

Pusillimonas caeni

EBR-8-1T, followed by

Pusillimonas noertemannii

BN9T (97.47 %),

Pusillimonas soli

MJ07T (96.93 %),

Parapusillimonas granuli

Ch07T (96.68 %),

Pusillimonas ginsengisoli

DCY25T (96.65 %),

Eoetvoesia caeni

PB3-7BT (96.63 %),

Paracandidimonas caeni

24T (96.34 %),

Castellaniella defragrans

54PinT (96.28 %) and

Pusillimonas harenae

B201T (96.05 %). L52-1-41 shared the highest 16S rRNA gene similarity of 97.74 % with

Pusillimonas caeni

EBR-8-1T, followed by

Pusillimonas noertemannii

BN9T (97.47 %),

Pusillimonas soli

MJ07T (96.65 %),

Parapusillimonas granuli

Ch07T (96.41 %),

Pusillimonas ginsengisoli

DCY25T (96.37 %),

Eoetvoesia caeni

PB3-7BT (96.35 %),

Pusillimonas harenae

B201T (96.28 %), and

Paracandidimonas caeni

24T (96.06 %). The results of phylogenetic analyses indicated that 17-4AT and L52-1-41 formed a stable, distinct and highly supported lineage affiliated to the genus

Pusillimonas

. The results of the digital DNA–DNA hybridization (dDDH) and average nucleotide identity (ANI) analyses indicated that they represented a single species. They featured similar genomic DNA G+C contents of 53.2–53.4 mol%. Activities of catalase and oxidase were negative for both strains. The fatty acids patterns of 17-4AT and L52-1-41 were most similar, mostly comprised of C16 : 0, C17 : 0cyclo, C18 : 0, C18 : 1ω9c and summed feature 8 (C18 : 1ω7c and/or C18 : 1
 ω6c). The major polar lipids of the two strains were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and unidentified aminolipids. The respiratory quinone of the two strains was Q-8. Hence, on the basis of the phenotypic, chemotaxonomic and genotypic data presented in this study, we proposed the classification of both strains as representatives of a novel species named Pusillimonas maritima sp. nov., with the type strain 17-4AT (=MCCC 1A12670T=KCTC 62121T=NBRC 113794T), and another strain L52-1-41 (=MCCC 1A05046=KCTC 52313).
Ability of quantitative PCR to discriminate Pneumocystis jirovecii pneumonia from colonization
Authors: Perret Thomas , Kritikos Antonios , Hauser Philippe M. , Guiver Malcolm , Coste Alix T. , Jaton Katia , Lamoth Frederic
Published: May 2020

Introduction.
Pneumocystis jirovecii pneumonia (PCP) is a severe disease affecting immunocompromised patients. Diagnosis is difficult due to the low sensitivity of direct examination and inability to grow the pathogen in culture. Quantitative PCR in bronchoalveolar lavage fluid (BAL) has high sensitivity, but limited specificity for distinguishing PCP from colonization.

Aim. To assess the performance of an in-house quantitative PCR to discriminate between PCP and colonization.

Methodology. This was a single-centre retrospective study including all patients with a positive PCR result for P. jirovecii in BAL between 2009 and 2017. Irrespective of PCR results, PCP was defined as the presence of host factors and clinical/radiological criteria consistent with PCP and (i) the presence of asci at direct examination of respiratory sample or (ii) anti-PCP treatment initiated with clinical response and absence of alternative diagnosis. Colonization was considered for cases who did not receive anti-PCP therapy with a favourable outcome or an alternative diagnosis. Cases who did not meet the above mentioned criteria were classified as ‘undetermined’.

Results. Seventy-one patients with positive P. jirovecii PCR were included (90 % non-HIV patients). Cases were classified as follows: 37 PCP, 22 colonization and 12 undetermined. Quantitative PCR values in BAL were significantly higher in patients with PCP versus colonization or undetermined (P<0.0001). The cut-off of 5×103 copies/ml was able to discriminate PCP cases from colonization with 97 % sensitivity, 82 % specificity, 90 % positive predictive value and 95 % negative predictive value.

Conclusions. Our quantitative PCR for P. jirovecii in BAL was reliable to distinguish PCP cases from colonization in this predominantly non-HIV population.
Transmission dynamics of coronavirus disease 2019 outside of Daegu-Gyeongsangbuk provincial region in South Korea
Authors: Ryu Sukhyun , Ali Sheikh Taslim , Jang Cheolsun , Kim Baekjin , Cowling Benjamin J.
Published: May 2020

We analyzed transmission of coronavirus disease 2019 in South Korea. We estimated that non-pharamaceutical measures reduced the immediate transmissibility by maximum of 34% for coronavirus disease 2019. Continuous efforts are needed for monitoring the transmissibility to optimize epidemic control.
Sensitivity evaluation of 2019 novel coronavirus (SARS-CoV-2) RT-PCR detection kits and strategy to reduce false negative
Authors: Zhou Yunying , Pei Fengyan , Wang Li , Zhao Huailong , Li Huanjie , Ji Mingyu , Yang Weihua , Wang Qingxi , Zhao Qianqian , Wang Yunshan
Published: May 2020

An ongoing outbreak of pneumonia associated with SARS-CoV-2 has now been confirmed globally. In absence of effective vaccines, infection prevention and control through diagnostic testing and quarantine is critical. Early detection and differential diagnosis of respiratory infections increases the chances for successful control of COVID-19 disease. The nucleic acid RT-PCR test is regarded as the current standard for molecular diagnosis with high sensitivity. However, the highest specificity confirmation target ORF1ab gene is considered to be less sensitive than other targets in clinical application. In addition, a large amount of recent evidence indicates that the initial missed diagnosis of asymptomatic patients with SARS-CoV-2 and discharged patients with “re-examination positive” may be due to low viral load, and the ability of rapid mutation of coronavirus also increases the rate of false negative results. We aimed to evaluate the sensitivity of different nucleic acid detection kits so as to make recommendations for the selection of validation kit, and amplify the suspicious result to be reportable positive by means of simple continuous amplification, which is of great significance for the prevention and control of the current epidemic and the discharge criteria of low viral load patients.
Vitamin D status, body mass index, ethnicity and COVID-19: Initial analysis of the first-reported UK Biobank COVID-19 positive cases (n 580) compared with negative controls (n 723)
Authors: Darling Andrea L. , Ahmadi Kourosh R. , Ward Kate A , Harvey Nicholas C , Alves Alexessander Couto , Dunn-Walters Deborah K. , Lanham-New Susan A. , Cooper Cyrus , Blackbourn David J.
Published: May 2020

In this short report we present a preliminary assessment of the serum 25-hydroxyvitamin D status (25(OH)D), body mass index (BMI), ethnicity and other lifestyle factors in the first-reported UK Biobank COVID-19 positive cases (n 580) compared with negative controls (n 723). The COVID-19 cases include those who have been treated as a hospital inpatient as well as those who have not, and are from England only. Mean (SD) for age was 57.5 (8.7) in positive cases and 57.9 (8.7) in negative controls.
Pre-Existing Traits Associated with Covid-19 Illness Severity
Authors: Ebinger Joseph E. , Achamallah Natalie , Ji Hongwei , Claggett Brian L. , Sun Nancy , Botting Patrick , Nguyen Trevor-Trung , Luong Eric , Kim Elizabeth H. , Park Eunice , Liu Yunxian , Rosenberry Ryan , Matusov Yuri , Zhao Steven , Pedraza Isabel , Zaman Tanzira , Thompson Michael , Raedschelders Koen , Berg Anders H. , Grein Jonathan D. , Noble Paul W. , Chugh Sumeet S. , Merz C. Noel Bairey , Marbán Eduardo , Van Eyk Jennifer E. , Solomon Scott D. , Albert Christine M. , Chen Peter , Cheng Susan
Published: May 2020

Background

Certain individuals, when infected by SARS-CoV-2, tend to develop the more severe forms of Covid-19 illness for reasons that remain unclear.

Methods

We studied N=442 patients who presented with laboratory confirmed Covid-19 illness to our U.S. metropolitan healthcare system. We curated data from the electronic health record, and used multivariable logistic regression to examine the association of pre-existing traits with a Covid-19 illness severity defined by level of required care: need for hospital admission, need for intensive care, and need for intubation.

Results

Of all patients studied, 48% required hospitalization, 17% required intensive care, and 12% required intubation. In multivariable-adjusted analyses, patients requiring a higher levels of care were more likely to be older (OR 1.5 per 10 years, P<0.001), male (OR 2.0, P=0.001), African American (OR 2.1, P=0.011), obese (OR 2.0, P=0.021), with diabetes mellitus (OR 1.8, P=0.037), and with a higher comorbidity index (OR 1.8 per SD, P<0.001). Several clinical associations were more pronounced in younger compared to older patients (Pinteraction<0.05). Of all hospitalized patients, males required higher levels of care (OR 2.5, P=0.003) irrespective of age, race, or morbidity profile.

Conclusions

In our healthcare system, greater Covid-19 illness severity is seen in patients who are older, male, African American, obese, with diabetes, and with greater overall comorbidity burden. Certain comorbidities paradoxically augment risk to a greater extent in younger patients. In hospitalized patients, male sex is the main determinant of needing more intensive care. Further investigation is needed to understand the mechanisms underlying these findings.
Simple ventilators for emergency use based on Bag-Valve pressing systems: Lessons learned and future steps
Authors: Castro-Camus E. , Ornik J. , Mach C. , Hernandez-Cardoso G. G. , Savalia B. , Taiber J. , Ruiz-Marquez A. , Kesper K. , Konde S. , Sommer C. , Wiener J. , Geisel D. , Hüppe F. , Kräling G. , Nguyen J. , Wiesmann T. , Beutel B. , Koch M.
Published: May 2020

As part of a plethora of global efforts to minimize the negative effects of the SARS-CoV2 (COVID-19) pandemic, we developed two different mechanisms that, after further development, could potentially be of use in the future in order to increase the capacity of ventilators with low-cost devices based on single-use-bag-valve mask systems. We describe the concept behind the devices and report a characterization of them. Finally, we make a description of the solved and unsolved challenges and propose a series of measures in order to better cope with future contingencies.
A model to estimate demand for personal protective equipment for Ontario acute care hospitals during the COVID-19 pandemic
Authors: Barrett Kali A , Nakamachi Yoshiko , Ierasts Terra , Khan Yasin , Mac Stephen , Naimark David , Stall Nathan , Ximenes Raphael , Morris Andrew , Sander Beate
Published: May 2020

In addition to instituting public health measures for COVID-19, managing healthcare resources is important for outcomes. The experiences in Italy and New York have shown that personal protective equipment (PPE) shortages can cause increased morbidity and mortality. We demonstrate a method to predict PPE demand across a health care system.
Forecasting Novel Corona Positive Cases in India using Truncated Information: A Mathematical Approach
Authors: Singh Brijesh P.
Published: May 2020

Novel corona virus is declared as pandemic and India is struggling to control this from a massive attack of death and destruction, similar to the other countries like China, Europe, and the United States of America. India reported 2545 cases novel corona confirmed cases as of April 2, 2020 and out of which 191 cases were reported recovered and 72 deaths occurred. The first case of novel corona is reported in India on January 30, 2020. The growth in the initial phase is following exponential. In this study an attempt has been made to model the spread of novel corona infection. For this purpose logistic growth model with minor modification is used and the model is applied on truncated information on novel corona confirmed cases in India. The result is very exiting that till date predicted number of confirmed corona positive cases is very close to observed on. The time of point of inflexion is found in the end of the April, 2020 means after that the increasing growth will start decline and there will be no new case in India by the end of July, 2020.
The Utility of rRT-PCR in Diagnosis and Assessment of Case-fatality rates of COVID-19 In the Iranian Population – Positive Test Results are a Marker for Illness Severity
Authors: Janbabaei Ghasem , Brandt Eric J. , Golpira Reza , Raeisi Alireza , Tabrizi Jafar Sadegh , Safikhani Hamid Reza , Talebian Mohammad Taghi , Samiee Siamak Mirab , Biglar Alireza , Malekzadeh Reza , Mani Arya
Published: May 2020

The utility of PCR-based testing in characterizing patients with COVID-19 and the severity of their disease remains unknown. We performed an observational study among patients presenting to hospitals in Iran who were tested for 2019-nCoV viral RNA by rRT-PCR between the fourth week of February 2020 to the fourth week of March 2020. Frequency of symptoms, comorbidities, intubation, and mortality rates were compared between COVID-19 positive vs. negative patients. 96103 patients were tested from 879 hospitals. 18754 (19.5%) tested positive for COVID-19. Positive testing was more frequent in those 50 years or older. The prevalence of cough (54.5% vs. 49.7%), fever (49.5% vs. 44.7%), and respiratory distress (43.0% vs. 39.0%) but not hypoxia (46.9% vs. 56.7%) was higher in COVID-19 positive vs. negative patients (p<0.001 for all). More patients had cardiovascular diseases (10.6% vs. 9.5%, p<0.001) and type 2 diabetes mellitus (10.8% vs. 8.7%, p<0.001) among COVID-19 positive vs. negative patients. There were fewer patients with cancer (1.1%, vs. 1.4%, p<0.001), asthma (1.9% vs. 2.5%, p<0.001), or pregnant (0.4% vs. 0.6%, =0.001) in COVID-19 positive vs. negative groups. COVID-19 positive vs. negative patients required more intubation (7.7% vs. 5.2%, p<0.001) and had higher mortality (14.6% vs. 6.3%, p<0.001). Odds ratios for death of positive vs negative patients range from 2.01 to 3.10 across all age groups. In conclusion, COVID-19 test-positive vs. test-negative patients had more severe symptoms and comorbidities, required higher intubation, and had higher mortality. rRT-PCR positive result provided diagnosis and a marker of disease severity in Iranians.
Chloroquine Administration in Breastfeeding Mothers Associates with Increased HIV-1 Plasma Viral Loads
Authors: Paxton William A , Naarding Marloes A , Wit Ferdinand WNM , Veldhuijzen Nienke J , Chersich Matthew F , Kankindi Brigitte , Douma Rene A , Tuyizere Samuel , Jurriaans Suzanne , Sparidans Rolf W , Beijnen Jos H , Pollakis Georgios , Boelaert Johan R , Lange Joep MA , Vyankandondera Joseph , Luchters Stanley
Published: May 2020

Chloroquine (CQ) and Hydroxychloroquine (HCQ) have been proposed to be effective at treating COVID-19 patients. We, and others, have previously reported on the capacity of CQ to reduce HIV-1 replication in vitro. We tested CQ administration in post-partum mothers on influencing HIV-1 viral loads in human milk as a means of lowering mother to child transmission. A Phase I/II, randomized, placebo-controlled study to evaluate chloroquine administration to reduce HIV-1 RNA levels in human milk: the CHARGE study. Thirty HIV-1 positive pregnant Rwandese women (CQ n = 20; placebo n = 10) were enrolled in a 16-week study, with the treatment group receiving a 200 mg oral dose of CQ daily. Base-line plasma viral load (pVL) measurements and CD4 counts were determined prior to delivery, and pVL, breast milk VL (bmVL) and CQ levels measured during treatment. For women receiving treatment, CQ concentration was higher in breast milk compared to plasma (over 2.5-fold), with a positive correlation between the levels in the two compartments (P < 0.003). A link between high CQ concentrations in plasma and high CD4 counts (P < 0.001) was observed. Surprisingly, we found a significant increase in pVL after CQ treatment in over half of the mothers (n=11; P < 0.001) and with no alteration to bmVL measurements. No specific amino acid alterations in the gp120 envelope sequences could be associated with CQ administration. CQ usage is associated with a significant increase to pVL in early breastfeeding mothers from Rwanda which cautions against the use of CQ in such individuals. Our results highlight a discrepancy between CQ effects on modulating HIV-1 replication in vitro versus in vivo and indicate caution when prescribing CQ to postpartum HIV-1 untreated mothers. This discrepancy should be taken into consideration when testing CQ or HCQ treatment in COVID-19 clinical trials, especially relating to the post-partum setting.
Modeling COVID-19 on a network: super-spreaders, testing and containment
Authors: Reich Ofir , Shalev Guy , Kalvari Tom
Published: May 2020

To model COVID-19 spread, we use an SEIR agent-based model on a graph, which takes into account several important real-life attributes of COVID-19: super-spreaders, realistic epidemiological parameters of the disease, testing and quarantine policies. We find that mass-testing is much less effective than testing the symptomatic and contact tracing, and some blend of these with social distancing is required to achieve suppression. We also find that the fat tail of the degree distribution matters a lot for epidemic growth, and many standard models do not account for this. Additionally, the average reproduction number for individuals, equivalent in many models to R0, is not an upper bound for the effective reproduction number, R. Even with an expectation of less than one new case per person, our model shows that exponential spread is possible. The parameter which closely predicts growth rate is the ratio between 2nd to 1st moments of the degree distribution. We provide mathematical arguments to argue that certain results of our simulations hold in more general settings.
Worldwide Effectiveness of Various Non-Pharmaceutical Intervention Control Strategies on the Global COVID-19 Pandemic: A Linearised Control Model
Authors: Naude Jacques , Mellado Bruce , Choma Joshua , Correa Fabio , Dahbi Salah , Dwolatzky Barry , Dwolatzky Leslie , Hayasi Kentaro , Lieberman Benjamin , Maslo Caroline , Monnakgotla Kgomotso , Ruan Xifeng , Stevenson Finn
Published: May 2020

Background
COVID-19 is a virus which has lead to a global pandemic. Worldwide, more than 130 countries have imposed severe restrictions, which form part of a set of non-pharmaceutical interventions (NPI)s. We aimed to quantify the country-specific effects of these NPIs and compare them using the Oxford COVID-19 Government Response Tracker (OxCGRT) stringency index, p, as a measure of NPI stringency.
Methods
We developed a dual latent/observable Susceptible Infected Recovered Deaths (SIRD) model and applied it on each of 22 countries and 25 states in the US using publicly available data. The observable model parameters were extracted using kernel functions. The regression of the transmission rate, β, as a function of p in each locale was modeled through the intervention leverage, αs, an initial transmission rate, β0 and a typical adjustment time, br-1.
Results
The world average for the intervention leverage, αs=0.01 (95% CI 0.0102 - 0.0112) had an ensemble standard deviation of 0.0017 (95% C.I. 0.0014 - 0.0021), strongly indicating a universal behavior.
Discussion
Our study indicates that removing NPIs too swiftly will result in the resurgence of the spread within one to two months, in alignment with the current WHO recommendations. Moreover, we have quantified and are able to predict the effect of various combinations of NPIs. There is a minimum NPI level, below which leads to resurgence of the outbreak (in the absence of pharmaceutical and clinical advances). For the epidemic to remain sub-critical, the rate with which the intervention leverage αs increases should outpace that of the relaxation of NPIs.
A non-parametric mathematical model to investigate the dynamic of a pandemic
Authors: Sosa Robert , Sosa Wilfredo
Published: May 2020

Populations are diverse in size, capacity response, and measures to contain a pandemic such covid19. Then, it rises serious and critical questions to whether general measures can be taken worldwide. Also, it is unclear if conventional parametric methods are suitable to study pandemics since their dynamic is modulated by biological, economical, environmental, social, and cultural factors. In this manuscript, we apply a recently developed non-parametric mathematical method that comes from regional economy, to investigate the dynamic of a pandemic. We apply this novel methodology to study the ongoing covid19 pandemic in all USA states and in the country itself. The generality of our methodology makes it suitable to investigate also the worldwide dynamics of diseases such HIV or tuberculosis.
Mathematical Mo Del with So Cial Distancing Parameter for Early Estimation of Covid-19 Spread
Authors: Chandra Saroj Kumar , Singh Avaneesh , Bajpai Manish Kumar
Published: May 2020

COVID-19 is well known to everyone in the world. It has spread around the world. No vaccine or antiviral treatment is available till now. COVID-19 patients are increasing day by day. All countries have adopted social distancing as a preventive measure to reduce spread. It becomes necessary to estimate the number of peoples going to be affected with COVID-19 in advance so that necessary arrangements can be done. Mathematical models are used to provide early disease estimation based on limited parameters. In the present manuscript, a novel mathematical model with a social distancing parameter has been proposed to provide early COVID-19 spread estimation. The model has been validated with real data set. It has been observed that the proposed model is more accurate in spread estimation.
Prediction of the Epidemic Peak of Covid19 in Egypt, 2020
Authors: El Desouky Eman D.
Published: May 2020

Objectives

Since December 2019 a pandemic of new novel coronavirus has started from Wuhan, China, in Egypt, the first case reported on February 14, 2020. In this study we aimed to predict the time of possible peak and simulate the changes could be happen by the social behavior of Egyptians during Ramadan (the holy month).

Methods

SIR and SEIR compartmental models were used to predict the peak time. We simulated different expected scenarios based to examine their effects on the peak timing.

Results

We found that the peak most likely to be in middle of June 2020. Simulating different transmission rate probability and R0 the earliest peak could to be in the May 20 and latest one could be in 18 July. The peak shifted much earlier to 11th April 2020 without lockdown and other mitigation strategies.

Conclusion

Social behaviors of citizens during the holy month will dramatically affect the peak timing. Mitigations strategies and other lockdown measure helped to delay the expected peak.
Transcriptome analyses of 7-day-old zebrafish larvae possessing a familial Alzheimer’s disease-like mutation inpsen1indicate effects on oxidative phosphorylation, mcm functions, and iron homeostasis
Authors: Dong Yang , Newman Morgan , Pederson Stephen , Hin Nhi , Lardelli Michael
Published: May 2020

Early-onset familial Alzheimer’s disease (EOfAD) is promoted by dominant mutations, enabling the study of Alzheimer’s disease (AD) pathogenic mechanisms through generation of EOfAD-like mutations in animal models. In a previous study, we generated an EOfAD-like mutation,psen1Q96_K97del, in zebrafish and performed a transcriptome analysis comparing entire brains from 6-month-old wild type and heterozygous mutant fish. We identified predicted effects on mitochondrial function and endolysosomal acidification. Here we aimed to determine whether similar effects occur in 7 day post fertilization (dpf) zebrafish larvae that might be exploited in screening of chemical libraries to find ameliorative drugs. We generated clutches of wild type and heterozygouspsen1Q96_K97del7 dpf larvae using a paired-mating strategy to reduce extraneous genetic variation before performing a comparative transcriptome analysis. We identified 228 differentially expressed genes and performed Goseq analysis and gene set enrichment analysis (GSEA). This predicted a significant effect on oxidative phosphorylation, consistent with our earlier observations of predicted effects on ATP synthesis in adult heterozygouspsen1Q96_K97delbrains. The dysregulation of minichromosome maintenance protein complex (MCM) genes strongly contributed to predicted effects on DNA replication and the cell cycle and may explain earlier observations of genome instability due toPSEN1mutation. The upregulation ofcrystallingene expression may be a response to defective activity of mutant Psen1 protein in endolysosomal acidification. Extracellular matrix (ECM) related genes were downregulated, consistent with previous studies of EOfAD mutant iPSC neurons and postmortem late onset AD brains. Also, changes in expression of genes controlling iron ion transport were observed without identifiable changes in the prevalence of transcripts containing iron responsive elements (IREs) in their 3’ untranslated regions. These changes may, therefore, predispose to the apparent iron dyshomeostasis previously observed in 6-month-old heterozygouspsen1Q96_K97delEOfAD-like mutant brains.
Closure motif-mediated state changes of the HORMA protein ASY1
Authors: Yang Chao , Hu Bingyan , Portheine Stephan Michael , Chuenban Pichaporn , Schnittger Arp
Published: May 2020

Meiotic HORMA domain-containing proteins (HORMADs) are key components of the chromosome axis and play an essential role in meiosis in many organisms. The meiotic HORMADs, including yeast Hop1, mouse HORMAD1 and HORMAD2, and Arabidopsis ASY1, assemble along chromosomes at early prophase and the closure motif at their C-termini has been hypothesized to be instrumental for this step by promoting HORMAD oligomerization. In late prophase, ASY1 and its homologs are progressively removed from synapsed chromosomes promoting chromosome synapsis and recombination. The conserved AAA+ ATPase PCH2/TRIP13 has been intensively studied for its role in removing HORMADs from synapsed chromosomes. In contrast, not much is known about how HORMADs are loaded onto chromosomes. Here, we reveal that the PCH2-mediated dissociation of the HORMA domain of ASY1 from its closure motif is important for the nuclear targeting and subsequent chromosomal loading of ASY1. This indicates that the promotion of ASY1 to an ‘unlocked’ state is a prerequisite for its nuclear localization and chromosomal assembly. Likewise, we find that the closure motif is also necessary for the removal of ASY1 by PCH2 later in prophase. Our work results in a grand unified model for PCH2 and HORMADs function in meiosis.
Oncogenic GLI1 and STAT1/3 activation drives immunosuppressive tryptophan/kynurenine metabolism via synergistic induction of IDO1 in skin cancer cells
Authors: Elmer Dominik P. , Strobl Victoria , Stockmaier Georg , Dang Hieu-Hoa , Wiederstein Markus , Licha David , Strobl Anna , Sternberg Christina , Tesanovic Suzana , Grund-Groeschke Sandra , Gruber Wolfgang , Wolff Florian , Moriggl Richard , Risch Angela , Reischl Roland , Huber Christian G. , Horejs-Hoeck Jutta , Aberger Fritz
Published: May 2020

Pharmacological targeting of Hedgehog (HH)/GLI has proven effective for certain blood, brain and skin cancers including basal cell carcinoma (BCC). However, limited response rates and the development of drug resistance call for improved anti-HH therapies that take into account synergistic crosstalk mechanisms and immune evasion strategies.

In previous work, we demonstrated that crosstalk of HH/GLI with pro-inflammatory Interleukin-6 (IL6) signaling drives BCC by promoting tumor cell proliferation [1]. In the present study, we screened for possible mechanisms of cancer immune evasion regulated by synergistic HH-IL6 signaling and identified the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO1) as a novel transcriptional target co-regulated by HH-IL6 signaling. Analysis of thecis-regulatory region of IDO1 by chromatin-immunoprecipitation revealed co-occupancy of this region by HH- IL6 induced GLI1 and STAT3 transcription factors along with active chromatin marks at the histone level. Elevated expression of IDO1 in human BCC with high-level HH and IL6 signatures supports the clinical relevance of our mechanistic data. Genetic inhibition of GLI1 expression prevented the induction of IDO1 expression in response to IL6/STAT3 and IFNγ/STAT1 signaling in human melanoma cells. Pharmacological targeting of HH signaling at the level of GLI proteins interfered with IDO1 expression and consequently prevented the production of the immunosuppressive metabolite kynurenine generated by active IDO1 from tryptophan. Further, inhibition of GLI1 enhanced the efficacy of the selective IDO1 inhibitor epacadostat. Of note, inhibition of HH/GLI signaling in melanoma cells not only reduced IDO1 expression but also interfered with the repression of T cell activation by attenuating IDO1/kynurenine-mediated immunosuppression. These data identify the immunosuppressive IDO1-kynurenine pathway as a novel pro-tumorigenic effector of oncogenic HH-IL6 and GLI-STAT cooperation. Our data suggest simultaneous pharmacological targeting of the HH/GLI, JAK/STAT and IDO1- kynurenine axis as rational combination therapy in skin cancers.
The paraventricular thalamus provides a polysynaptic brake on limbic CRF neurons to sex-dependently blunt binge alcohol drinking and avoidance behavior
Authors: Levine Olivia B. , Skelly Mary Jane , Miller John D. , Rivera-Irizarry Jean K. , Rowson Sydney A. , DiBerto Jeffrey F. , Rinker Jennifer A. , Thiele Todd E. , Kash Thomas L. , Pleil Kristen E.
Published: May 2020

Bed nucleus of the stria terminalis (BNST) neurons that synthesize and release the stress neuropeptide corticotropin-releasing factor (CRF) drive binge alcohol drinking and anxiety, behaviors that are primary risk factors for alcohol use disorder (AUD) and comorbid neuropsychiatric diseases more common in women than men. Here, we show that female C57BL/6J mice binge drink more than males and have greater basal BNSTCRFneuron excitability and synaptic excitation. We identified a dense VGLUT2+ glutamatergic synaptic input from the paraventricular thalamus (PVT) that is anatomically similar in males and females. These PVTBNSTneurons release glutamate directly onto BNSTCRFneurons but also engage a large BNST interneuron population to ultimately provide a net inhibition of BNSTCRFneurons, and both components of this polysynaptic PVTVGLUT2-BNSTCRFcircuit are more robust in females than males. Chemogenetic inhibition of the PVTBNSTprojection promoted binge alcohol drinking in females without affecting males, and chemogenetic activation of the pathway was sufficient to reduce avoidance behavior in both sexes in anxiogenic contexts. Lastly, we show that withdrawal from repeated binge drinking produces a female-like phenotype in the male PVT-BNSTCRFexcitatory synapse without altering the function of PVTBNSTneuronsper se. Our data describe a complex feedforward inhibitory PVTVGLUT2-BNSTCRFglutamatergic circuit that is more robust in females, plays sex-dependent roles in alcohol drinking and avoidance behavior, and undergoes sex-dependent alcohol-induced plasticity.
Mechanism and function of root circumnutation
Authors: Taylor Isaiah , Lehner Kevin , McCaskey Erin , Nirmal Niba , Ozkan-Aydin Yasemin , Murray-Cooper Mason , Jain Rashmi , Hawkes Elliot W. , Ronald Pamela C. , Goldman Daniel I. , Benfey Philip N.
Published: May 2020

Early root growth is critical for plant establishment and survival. We have identified a molecular pathway required for oscillatory root tip movement known as circumnutation. Here we report a multiscale investigation of the regulation and function of this phenomenon. We identify key cell signaling events comprising interaction of the ethylene, cytokinin, and auxin hormone signaling pathways. We identify the geneOryza sativa Histidine Kinase-1/OsHK1, as well as the auxin influx carrier geneOsAUX1, as essential regulators of this process in rice. Robophysical modelling demonstrated the benefits of tip movement for navigating past obstacles, prompting us to challenge mutant and wild-type plants with different substrates. Consistent with model behavior, root circumnutation facilitated exploration of a solid surface and promoted seedling establishment in rocky soil. Thus, the integration of robotics, physics and biology elucidated the functional importance of root circumnutation and uncovered the molecular mechanisms underlying its regulation.

One sentence summary

Circumnutation facilitates root exploration.
Mass spectrometric method for the unambiguous profiling of cellular dynamic glycosylation
Authors: Shajahan Asif , Supekar Nitin T. , Wu Han , Wands Amberlyn M. , Bhat Ganapati , Kalimurthy Aravind , Matsubara Masaaki , Ranzinger Rene , Kohler Jennifer J. , Azadi Parastoo
Published: May 2020

Various biological processes at the cellular level are regulated by glycosylation which is a highly micro-heterogeneous post-translational modification (PTM) on proteins and lipids. The dynamic nature of glycosylation can be studied through bio-orthogonal tagging of metabolically engineered non-natural sugars into glycan epitopes. However, this approach possesses a significant drawback due to non-specific background reactions and ambiguity of non-natural sugar metabolism. Here we report a tag-free strategy for their direct detection by glycoproteomics and glycomics using mass spectrometry. The method dramatically simplifies the detection of non-natural functional group bearing monosaccharides installed through promiscuous sialic acid, GalNAc, and GlcNAc biosynthetic pathways. Multistage enrichment of glycoproteins by cellular fractionation, subsequent ZIC-HILIC based glycopeptide enrichment, and a spectral enrichment algorithm for the MS data processing enabled direct detection of non-natural monosaccharides that are incorporated at low abundance on the N/O-glycopeptides along with their natural counterparts. Our approach allowed the detection of both natural and non-natural sugar bearing glycopeptides, N and O-glycopeptides, differentiation of non-natural monosaccharide types on the glycans and also their incorporation efficiency through quantitation. Through this we could deduce some interconversion of monosaccharides during their processing through glycan salvage pathway and subsequent incorporation into glycan chains. The study of glycosylation dynamics through this method can be conducted in high throughput as few sample processing steps are involved, enabling understanding of glycosylation dynamics under various external stimuli and thereby could bolster the use of metabolic glycan engineering in glycosylation functional studies.
A consistent evaluation of miRNA-disease association prediction models
Authors: Dong Ngan Thi , Khosla Megha
Published: May 2020

Motivation

A variety of machine learning based approaches have been applied to predicting miRNA-disease association. Although promising, the evaluation set up to measure prediction performance is inconsistent making it difficult to assess the actual progress. A more acute problem is that most of the models overlook the problem of data leakage due to the use of precomputed miRNA and disease similarity features.

Results

We unearth a crucial problem of data leakage in evaluation of machine learning models for miRNA-disease association prediction. In particular, information from test set, in the form of precomputed input features for miRNA and disease, is used during training of the model. Moreover, we point out problems in the widely used performance metrics used in model evaluation. While resolving the issues of data leakage and model evaluation, we perform an indepth study of 3 recent models along with our proposed 9 variants of these models. Our proposed variants have resulted in improvements in Average Precision scores (as compared to original models) by approximately 287.7% and 36.7% on HMDDv2.0 (AP:0.504) and HMDDv3.0 (AP: 0.216) datasets respectively.

Availability and Implementation

We release a unified evaluation framework including all models and datasets athttps://git.l3s.uni-hannover.de/dong/simplifying_mirna_disease.
Inference of Population Admixture Network from Local Gene Genealogies: a Coalescent-based Maximum Likelihood Approach
Authors: Wu Yufeng
Published: May 2020

Population admixture is an important subject in population genetics. Inferring population demographic history with admixture under the so-called admixture network model from population genetic data is an established problem in genetics. Existing admixture network inference approaches work with single genetic variation sites. While these methods are usually very fast, they don’t fully utilize the information (e.g., linkage disequilibrium or LD) contained in population genetic data. In this paper, we develop a new admixture network inference method called GTmix. Different from existing methods, GTmix works with local gene genealogies that can be inferred from population haplotypes. Local gene genealogies represent the evolutionary history of sampled alleles and contain the LD information. GTmix performs coalescent-based maximum likelihood inference of admixture networks with the inferred genealogies based on the well-known multispecies coalescent (MSC) model. GTmix utilizes various techniques to speed up likelihood computation on the MSC model and optimal network search. Our simulations show that GTmix can infer more accurate admixture networks with much smaller data than existing methods, even when these existing methods are run with much larger data. GTmix is reasonably efficient and can analyze genetic datasets of current interests.
Multistep substrate binding and engagement by the AAA+ ClpXP protease
Authors: Saunders Reuben A. , Stinson Benjamin M. , Baker Tania A. , Sauer Robert T.
Published: May 2020

E. coliClpXP is one of the most thoroughly studied AAA+ proteases, but relatively little is known about the reactions that allow it to bind and then engage specific protein substrates before the ATP-fueled mechanical unfolding and translocation steps that lead to processive degradation. Here, we employ a fluorescence-quenching assay to study the binding of ssrA-tagged substrates to ClpXP. Polyphasic stopped-flow association and dissociation kinetics support the existence of at least three distinct substrate-bound ClpXP complexes. These kinetic data fit well to a model in which ClpXP and substrate form an initial binding complex, followed by an intermediate complex, and then an engaged complex that is competent for substrate unfolding. The initial association and dissociation steps do not require ATP hydrolysis, but subsequent forward and reverse kinetic steps are accelerated by faster ATP hydrolysis. Our results, together with recent cryo-EM structures of ClpXP bound to substrates, support a model in which the ssrA degron initially binds in the top portion of the axial channel of the ClpX hexamer and then is translocated deeper into the channel in steps that eventually pull the native portion of the substrate against the channel opening. Reversible initial substrate binding allows ClpXP to check potential substrates for degrons, potentially increasing specificity. Subsequent substrateengagement steps allow ClpXP to grip a wide variety of sequences to ensure efficient unfolding and translocation of almost any native substrate.

Significance

AAA+ proteases play key regulatory and quality-control roles in all domains of life. These destructive enzymes recognize damaged, unneeded, or regulatory proteins via specific degrons and unfold them prior to processive degradation. Here, we show thatE. coliClpXP, a model AAA+ protease, recognizes ssrA-tagged substrates in a multistep binding and engagement reaction. Together with recent cryo-EM structures, our experiments reveal how ClpXP transitions from a machine that checks potential substrates for appropriate degrons to one that can unfold and translocate almost any protein. Other AAA+ proteases in organelles and bacteria are likely to use similar mechanisms to specifically identify and then destroy their target proteins.
Identification and selection of optimal reference genes for qPCR-based gene expression analysis inFucus distichusunder various abiotic stresses
Authors: Linardić Marina , Braybrook Siobhan A
Published: May 2020

Quantitative gene expression analysis is an important tool in the scientist’s belt. The identification of evenly expressed reference genes is necessary for accurate quantitative gene expression analysis, whether by traditional RT-PCR (reverse-transcription polymerase chain reaction) or by qRT-PCR (quantitative real-time PCR; qPCR). In the Stramenopiles (the major line of eukaryotes that includes brown algae) there is a noted lack of known reference genes for such studies, largely due to the absence of available molecular tools. Here we present a set of nine reference genes (Elongation Factor 1 alpha (EF1A), Elongation Factor 2 alpha (EF2A), Elongation Factor 1 beta (EF1B), 14-3-3 Protein, Ubiquitin Conjugating Enzyme (UBCE2), Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH), Actin Related Protein Complex (ARP2/3), Ribosomal Protein (40s; S23), and Actin) for the brown algaFucus distichus. These reference genes were tested on adult sporophytes across six abiotic stress conditions (desiccation, light and temperature modification, hormone addition, pollutant exposure, nutrient addition, and wounding). Suitability of these genes as reference genes was quantitatively evaluated across conditions using standard methods and the majority of the tested genes were evaluated favorably. However, we show that normalization genes should be chosen on a condition-by-condition basis. We provide a recommendation that at least two reference genes be used per experiment, a list of recommended pairs for the conditions tested here, and a procedure for identifying a suitable set for an experimenter’s unique design. With the recent expansion of interest in brown algal biology and accompanied molecular tools development, the variety of experimental conditions tested here makes this study a valuable resource for future work in basic biology and understanding stress responses in the brown algal lineage.