bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluctuating Weak Magnetic Fields Induce Marked Mitophagy
Authors: Toda Takuro , Ito Mikako , Mori Kaneo , Ohno Kinji 
Published: April 2020

Previous epidemiological studies have revealed that occupational exposure to extremely low frequency weak magnetic fields (ELF‐WMF) is associated with the development of neurodegenerative diseases including Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS). The molecular mechanism of these detrimental effects, however, remain mostly unelucidated.We examined the effects of extremely low frequency fluctuation of weak magnetic fields (ELF‐WMF) on cultured mammalian cells. While applying ELF‐WMF, we examined the temporal profiles of expression levels of VDAC1, a mitochondrial outer membrane protein, and seven electron transport complex (ETC) proteins of NDUFS1 (ETC I), NDUFB8 (ETC I), SDHB (ETC II), UQCRFS1 (ETC III), UQCRC2 (ETC III), MTCOI (ETC IV), and ATP5A (ETC V). ELF‐WMF downregulated the amounts of these proteins at 3 h and recovered them at 12 h. Quantification of the amount of mitochondria with MitoTracker Green showed that the mitochondrial mass was decreased to 70% at 3 h and recovered at 12 h. In addition, mitophagy‐related proteins of PINK1 and LC3‐II were increased by ELF‐WMF at 1.5–2.5 h. Quantification of ETC enzymatic activities in protein homogenates revealed that ELF‐WMF exclusively suppressed the activity of ETC II in 10 min.We report that ELF‐WMF much weaker than geomagnetic fields suppresses the enzymatic activity of ETC II, and provokes mitophagy. Mitophagy is a cellular quality‐assurance system to eliminate damaged mitochondria. Mitophagy induced by ELF‐WMF may be causally associated with the development and progression of AD and ALS. Contrarily, ELF‐WMF finely tuned to preferentially eliminate damaged mitochondria may be able to ameliorate Parkinson’s disease, in which compromised mitophagy is a cause of the disease.Support or Funding InformationThis research was supported by grants‐in‐aids from MEXT, MHLW, and AMED of Japan.
Structure and functions of the Mediator complex: A key regulator of RNA polymerase II transcription
Authors: SATO Shigeo , Tomomori-Sato Chieri , Ranjan Amol , Conaway Ronald C. , Conaway Joan W. 
Published: April 2020

In eukaryotic cells from yeast to humans, the multi‐subunit Mediator complex contributes to transcriptional regulation of RNA polymerase II (Pol II) by acting as a coregulator. The Mediator regulates multiple stages of transcription by interacting with gene‐specific transcription factors, Pol II, and factors that regulate Pol II initiation and elongation. Mediator also affects the activities of factors involved in mRNA processing and chromatin regulation. Because of its central role in transcription, Mediator modulates pathways linked to cell differentiation, cell growth, and tissue development.Metazoan Mediator is composed of over 30 subunits in organized into several modules. In metazoa, Mediator core, composed of head, middle, and tail modules, can interact with a dissociable subunit called MED26. When isolated from cells, a large fraction of MED26‐containing Mediator is associated with Pol II; however, it remains unclear whether or how MED26 contributes to the Mediator‐Pol II interaction. A second form of Mediator lacks MED26 and instead binds a dissociable kinase module containing one of two kinase‐cyclin pairs, CDK8/Cyclin C or CDK19/Cyclin C. Because kinase module interferes with binding of the Mediator core to Pol II, it was proposed that Mediator associated with kinase module might function as a repressive cofactor; however, more recent results from multiple labs supports the model that both MED26‐Mediator and kinase module‐associated Mediator contribute to gene activation.A major focus of our research is to understand how these two forms of Mediator are involved in transcription regulation. Ongoing experiments seek to explore mechanisms that regulate Mediator‐Pol II interactions. In particular, we wish to understand (i) how Mediator recognizes Pol II and how the Mediator‐Pol II interaction is maintained, (ii) how Mediator is released from Pol II after transcription initiation, and (iii) whether and how the kinase module and MED26 contribute to each of these processes.Support or Funding InformationThe Stowers Institute for Medical ResearchThe Helen Nelson Medical Research Fund at Greater Kansas City Community Foundation
STUB Network: Statisticians and Biologists Improving Statistics Education in Introductory Biology
Authors: Keeling Elena , Bunting Jamie , Chance Beth , Roy Soma , Blank Jason , Tintle Nathan 
Published: April 2020

Introductory biology courses typically incorporate data collection and analysis into laboratory assignments, and therefore teach some basic statistics. However, these curricula are generally developed without input from statisticians and are taught by instructors, often graduate students, with a range of experience using statistics but no training in statistics education. Given the importance of statistical thinking and other quantitative approaches in biology, the Statistical Thinking in Undergraduate Biology (STUB) network was established to facilitate coordination of best practices and assessment of statistical thinking in introductory biology students. As an example of the network’s benefits, we present a case study involving redesign of laboratory activities in an Introduction to Organismal Form and Function course. Changes include alignment of language with that used in statistics courses, more thorough instruction about experimental design and statistical tests, and use of an online simulation tool shown to improve understanding of statistical inference in statistics courses. These changes are supported by statistics faculty participating in the training of biology teaching assistants. An assessment in progress compares conceptual understanding and attitudes toward statistics before and after the redesigned lab activity; the assessment tool is being used throughout the STUB network, providing comparable data across institutions. This kind of cross‐disciplinary collaboration has the potential to improve statistical thinking in undergraduate biology students, better preparing them for advanced coursework and for careers in modern biology.Support or Funding InformationNSF Research Coordination Network‐Undergraduate Biology Education (RCN‐UBE)
Electron Scavenging Not Free Radical Scavenging by Fullerene Materials Protects Against Mitochondrial Oxidative Stress in Complex Organisms.
Authors: Bourassa Daniel J. , Tulp Orien Lee , Einstein George P. 
Published: April 2020

Fullerene materials are often reported to be excellent antioxidants in cells. Usually, direct free radical scavenging mechanisms, as seen in polymer and food industry research, is the proposed antioxidant mechanism. However, free radical scavenging by antioxidants in vivo is kinetically unlikely and conflicts with fullerene material’s molecular properties. Pristine fullerene materials, and many of their derivatives, are pro‐oxidant and form adducts, which are both potentially toxic mechanisms in vivo. Although they are electrophilic, and potentially oxidative molecules with an affinity for electrons, they appear to function like other non‐radical electrophilic antioxidants and stimulate enzymatic oxidative stress management and protection. We approach fullerene material’s antioxidant role from the perspective that they do not act as direct free radical scavengers. Other mechanisms have been previously proposed that are more consistent with fullerene properties, and antioxidant benefits in vivo. Here we discuss fullerene materials as electron scavenging antioxidants rather than free radical scavengers. We propose that fullerene materials scavenge excess electrons in the ETC preventing the formation of superoxide and hydroxyl radicals in the mitochondria. The scavenging of electrons would help in preventing damage to mitochondrial structures and DNA, maintaining optimum NAD+/NADH ratios, as well as in maintaining an oxidized OX/PHOS enzyme system in mitochondrial conditions resulting from excess caloric intake in the absence of cellular energy requirements and progressive mitochondrial dysfunction related to oxidative stress. Further research is needed to evaluate the utilization of fullerene materials for use in metabolic syndromes and neurodegenerative conditions complicated by progressive mitochondrial damage.Support or Funding InformationSupported by Institutional Resources of the University of Science Arts and Technology, Montserrat, BWI, The University of Health and Humanities, BVI and the Einstein Medical Institute, Florida USA.
MiR 208a Deficiency Promotes Mitochondrial Biogenesis in the metabolic heart
Authors: Rosca Mariana Georgeta , Mekala Naveen , Kurdys Jacob G. , Vicenzi Alexis , Avramut Carmen , Ragina Neli Petrova 
Published: April 2020

A high caloric regimen causes metabolic syndrome, which is a pre‐requisite for type 2 diabetes mellitus, and increases the risk for cardiovascular disease. Both metabolic syndrome and diabetes induce a common cardiac phenotype known as metabolic cardiomyopathy with an early onset as diastolic dysfunction that may progress to systolic dysfunction and congestive heart failure.While the normal heart is able to freely switch between glucose and fatty acid (FA) oxidation, the metabolic heart becomes almost completely reliant on FA oxidation for ATP production. This energetic dysregulation is supported by increased mitochondrial metabolism, which includes an increased mitochondrial mass and function. Based on the reported cardiac specificity of the microRNA (miR) 208a, we investigated its role in bioenergetic metabolism in the metabolic heart. Lewis rats exposed to a high fat diet (HFD) exhibit obesity, systemic insulin resistance, hyperglycemia, hyperlipidemia, cardiac diastolic dysfunction, and cardiac fibrosis. Microarray studies highlighted an altered miRNA expression profile in the heart upon HFD, including a decrease in miR 208a. CRISPR deletion of the miR 208a in cultured human SV40 cardiomyocytes exposed to diabetogenic conditions (high glucose, high albumin‐bound palmitate) led to a bioenergetics profile that favors mitochondrial FA metabolism including an increase in mitochondrial biogenesis signaling, electron transport chain complexes and critical enzymes for FA beta‐oxidation. In addition, miR 208‐a deficiency prevented the switch in the myosin heavy chain isoforms by increasing myosin heavy chain alpha, thus preserving cardiac contractility. We analyzed in silico for putative miR 208a targets focusing on mitochondrial outcomes using the TargetScanHuman database (
http://www.targetscan.org/cgi‐bin/targetscan/vert_71/targetscan.cgi). We found that mitochondrial ribosomal protein 28 (involved in mitochondrial translation and generation of mitochondrial DNA‐encoded electron transport chain subunits), MINOS1 (a conserved component of mitofilin complexes required for mitochondrial function and cristae organization), and MED7 (component of the Mediator Complex that regulates the transcription by facilitating the interaction between nuclear receptors, transcriptional co‐activator and co‐repressors, and chromatic modification factors with RNA Pol II) are rescued by miR 208a deficiency in cardiomyocytes exposed to diabetogenic conditions. In summary, miR 208a regulates nuclear and mitochondrial transcription, mitochondrial cristae organization and integrity in the diabetic heart, and supports the metabolic remodeling towards increased FA oxidation. Our data suggest that miR 208a may be a therapeutic target to promote mitochondrial biogenesis in chronic diseases associated with mitochondrial defects.Support or Funding InformationCentral Michigan University Early Career Grant, AIREA American Heart Association
Feeding Patterns and Medical Diagnosis Frequency in a National Survey of Older Dogs
Authors: Hollar Regina L. , Schiefelbein Heidi M. , Stone Becky A. , MacLeay Jennifer M. , Wernimont Susan M. 
Published: April 2020

Veterinarians and owners are often concerned with the nutrition of dogs, but most knowledge of real‐world pet feeding practices is anecdotal. A survey was conducted among owners of dogs aged ≥ 5 yrs at general practice veterinary clinics across the United States (2016–2017). Owners participated in a clinic visit with their dog, and demographics including age and breed were collected. Veterinarians documented the dog’s medical history and completed a physical exam including Body Fat Index (BFI) rated using a visual scale. Owners completed a nutrition survey by estimating the proportions of dry, wet, human food, treats, and other foods (including homemade petfoods) offered to their dog the prior day. Complete nutrition survey information was obtained from 992 dogs (5.0 to 20.8 yrs, median 9.4 yrs); of these 982 (99%) had complete medical histories. Dogs represented 15 states: PA (17%), CO (17%), NY (12.7%), IL (8.5%), VA (7.9%), FL (7.8%), MO (6.8%), NJ (5.0%), MI (4.6%), MD (4.5%), TX (3.3%), LA (2.5%), GA (1.5%), CT (0.6%), and CA (0.2%). In addition to mixed breeds, 115 dog breeds were reported by owners, most commonly: Labrador Retriever (13.1%), Golden Retriever (5.3%), Shih Tzu (3.9%), Other (3.7%), German Shepherd (3.7%), Dachshund (3.3%), Yorkshire Terrier (3.1%), Beagle (2.7%), Bichon Frise (2.6%) and Pug (2.4%). Giant breeds together represented 3.8% of all dogs. The 10 most common diagnoses observed in the medical history were mild/moderate dental/gum disease: 83.7%, benign tumors (including lipomas): 46.2%, overweight/obese: 34.8%, otitis (in which atopic dermatitis was ruled out): 20.3%, arthritis (elbow, stifle, back, and/or neck): 19.6%, atopic dermatitis: 15.3%, hypothyroidism: 13.1%, sebaceous cysts: 11.3%, arthritis of the hip: 10.7%, urinary tract infection: 10.0%. BFI as assessed by vets at the time of the survey ranged from 10 to 70, median 30; 69.2% dogs had a BFI of 20 or 30 while 23.5% had a BFI of 40 or more. 92.5% of dogs were offered any dry food while 72.6% of dogs were offered ≥ 90% of their intake as dry food and 19.5% of dogs were offered exclusively dry food. 23.6% of dogs were offered any wet food; 2.6% were offered ≥ 90% of their intake as wet food and only 0.7% of dogs were offered exclusively wet food. 58.8% of dogs were offered any treats, 32.0% of dogs were offered any human food, and 5.0% were offered other food, including homemade petfoods. Most owners of older dogs fed predominantly dry food and only a minority fed wet food exclusively. Treats and human food were commonly offered. The frequency of breeds and diagnoses observed in this population were generally similar to other national surveys; this analysis provides important information about feeding patterns among older dogs.Support or Funding InformationThis study was funded by Hill’s Pet Nutrition, Inc.
Revealing variants in SARS-CoV-2 interaction domain of ACE2 and loss of function intolerance through analysis of >200,000 exomes
Authors: Cirulli Elizabeth T. , Riffle Stephen , Bolze Alexandre , Washington Nicole L. 
Published: April 2020

Lay summaryOur researchers took a look at a sequence of DNA known as theACE2gene. This gene is most well known for its role in regulating blood pressure. But in recent times, it’s drawn a lot of attention from the scientific community because it may also serve as a doorway of sorts, enabling viruses like SARS-CoV-2 to infect cells. Our researchers looked at theACE2gene in more than 200,000 people, comparing their exact DNA sequences to see where there are differences among people. Variation in the DNA sequence of a gene is common and is sometimes meaningless. But other times, small changes in the DNA sequence can alter the protein that is made from that gene. In this case theACE2gene makes the ACE2 protein, which is what the SARS-CoV-2 virus interacts with. We found a lot of variation between individuals and checked to see if that variation coincided with any traits (i.e., people with variant X tend to have high blood pressure more often than people without variant X). All of the traits we looked at were non-COVID-19-related traits, meaning we haven’t asked these people anything about COVID-19 yet (this is because these DNA sequences were collected before the pandemic).We found that there are a number of variations observed among people in a specific part of theACE2gene. These variations are expected to alter the shape or functionality of a specific part of the ACE2 protein: The part that interacts with the SARS-CoV-2 virus. We don’t yet know what the real-life significance of this variation is, but it’s possible that these variants decrease the protein’s ability to interact with the SARS-CoV-2 virus, thus decreasing the person’s likelihood of being infected. We can speculate that there will be a spectrum of vulnerability to COVID-19 among people, where some people are more vulnerable than others, and that variants in this part of theACE2gene may be one of the reasons. The research we presented here shines a light on this part of theACE2gene and may give future researchers a direction to go in as they try to figure out what makes people vulnerable to COVID-19 and similar viruses.
Improving Coronavirus (COVID-19) Diagnosis using Deep Transfer Learning
Authors: Rehman Arshia , Naz Saeeda , Khan Ahmed , Zaib Ahmad , Razzak Imran 
Published: April 2020

AbstractBackgroundCoronavirus disease (COVID-19) is an infectious disease caused by a new virus. Exponential growth is not only threatening lives, but also impacting businesses and disrupting travel around the world.AimThe aim of this work is to develop an efficient diagnosis of COVID-19 disease by differentiating it from viral pneumonia, bacterial pneumonia and healthy cases using deep learning techniques.MethodIn this work, we have used pre-trained knowledge to improve the diagnostic performance using transfer learning techniques and compared the performance different CNN architectures.ResultsEvaluation results using K-fold (10) showed that we have achieved state of the art performance with overall accuracy of98.75%on the perspective of CT and X-ray cases as a whole.ConclusionQuantitative evaluation showed high accuracy for automatic diagnosis of COVID-19. Pre-trained deep learning models develop in this study could be used early screening of coronavirus, however it calls for extensive need to CT or X-rays dataset to develop a reliable application.
Lockdowns to Contain COVID-19 Increase Risk and Severity of Mosquito-Borne Disease Outbreaks
Authors: Jindal Akshay , Rao Shrisha 
Published: April 2020

AbstractMany countries are implementing lockdown measures to slow the COVID-19 pandemic, putting more than a third of the world’s population under restrictions. The scale of such lockdowns is unprecedented, and while some effects of lockdowns are readily apparent, it is less clear what effects they may have on outbreaks of serious communicable diseases. We examine the impact of these lockdowns on outbreaks of mosquito-borne diseases. Using an agent-based model and simulations, we find that the risk and severity of such outbreaks is much greater under lockdown conditions, with the number of infected people doubling in some cases. This increase in number of cases varies by different mosquito-borne diseases, and is significantly higher for diseases spread by day-biting mosquitoes. We analysed various intervention strategies and found that during lockdowns, decentralised strategies such as insecticide-treated nets and indoor residual spraying are more effective than centralised strategies.
Lopinavir/ritonavir for the treatment of COVID-19: A living systematic review protocol
Authors: Verdugo-Paiva Francisca , Izcovich Ariel , Ragusa Martín , Rada Gabriel 
Published: April 2020

ABSTRACTObjectiveTo assess the efficacy and safety of lopinavir/ritonavir for the treatment of patients with COVID-19.DesignThis is the protocol of a living systematic review.Data sourcesWe will conduct searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), grey literature and in a centralised repository in L·OVE (Living OVerview of Evidence). L·OVE is a platform that maps PICO questions to evidence from Epistemonikos database. In response to the COVID-19 emergency, L·OVE was adapted to expand the range of evidence it covers and customised to group all COVID-19 evidence in one place. The search will cover the period until the day before submission to a journal.Eligibility criteria for selecting studies and methodsWe adapted an already published common protocol for multiple parallel systematic reviews to the specificities of this question.We will include randomised trials evaluating the effect of lopinavir/ritonavir— as monotherapy or in combination with other drugs — versus placebo or no treatment in patients with COVID-19. Randomised trials evaluating lopinavir/ritonavir in infections caused by other coronaviruses, such as MERS-CoV and SARS-CoV, and non-randomised studies in COVID-19 will be searched in case no direct evidence from randomised trials is found, or if the direct evidence provides low- or very low-certainty for critical outcomes.Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will perform random-effects meta-analyses and use GRADE to assess the certainty of the evidence for each outcome.A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it if the conclusions change or there are substantial updates.Ethics and disseminationNo ethics approval is considered necessary. The results of this review will be widely disseminated via peer-reviewed publications, social networks and traditional media.PROSPERO RegistrationSubmitted to PROSPERO (awaiting ID allocation).