bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding phase-amplitude coupling from bispectral analysis
Authors: Zandvoort Coen S. , Nolte Guido 
Published: March 2020

AbstractTwo measures of cross-frequency coupling (CFC) are Phase-Amplitude Coupling (PAC) and bicoherence. The estimation of PAC with meaningful bandwidth for the high frequency amplitude is crucial in order to avoid misinterpretations. While recommendations on the bandwidth of PAC’s amplitude component exist, there is no consensus yet. Here, we show that the earlier recommendations on filter settings lead to estimates which are smeared in the frequency domain, which makes it difficult to distinguish higher harmonics from other types of CFC. We also show that smearing can be avoided with a different choice of filter settings by theoretically relating PAC to bicoherence. To illustrate this, PAC estimates of simulations and empirical data are compared to bispectral analyses. We used simulations replicated from an earlier study and empirical data from human electro-encephalography and rat local field potentials. PAC’s amplitude component was estimated using a bandwidth with a ratio of (1) 2:1, (2) 1:1, or (3) 0.5:1 relative to the frequency of the phase component. For both simulated and empirical data, PAC was smeared over a broad frequency range and not present when the estimates comprised a 2:1- and 0.5:1-ratio, respectively. In contrast, the 1:1-ratio accurately avoids smearing and results in clear signals of CFC. Bicoherence estimates, which do not smear across frequencies by construction, were found to be essentially identical to PAC calculated with the recommended frequency setting.
Adaptable pulsatile flow generated by quantitative imaging of stem-cell derived cardiomyocytes for disease modeling
Authors: Qian Tongcheng , Gil Daniel A. , Guzman Emmanuel Contreras , Gastfriend Benjamin D. , Tweed Kelsey E. , Palecek Sean P. , Skala Melissa C. 
Published: March 2020

AbstractEndothelial cells (EC)in vivoare continuously exposed to a mechanical microenvironment from blood flow, and fluidic shear stress plays an important role in EC behavior. New approaches to generate physiologically and pathologically relevant pulsatile flows are needed to understand EC behavior under different shear stress regimes. Here, we demonstrate an adaptable pump (Adapt-Pump) platform for generating pulsatile flows via quantitative imaging of human pluripotent stem cell-derived cardiac spheroids (CS). Pulsatile flows generated from the Adapt-Pump system can recapitulate unique CS contraction characteristics, accurately model responses to clinically relevant drugs, and simulate CS contraction changes in response to fluidic mechanical stimulation. We discovered that ECs differentiated under a long QT syndrome derived pathological pulsatile flow exhibit abnormal EC monolayer organization. This Adapt-Pump platform provides a powerful tool for modeling the cardiovascular system and improving our understanding of EC behavior under different mechanical microenvironments.
Versatile Method to measure locomotion
Authors: Barwell Taylor , Raina Sehaj , Seroude Laurent 
Published: March 2020

AbstractMany studies require the ability to quantify locomotor behavior over time. The list of tracking softwares and their capabilities are constantly growing. At the 2019 CanFly Conference we presented preliminary results from an investigation of the effects of expressing polyglutamine repeats in fly muscles on longevity, locomotion and protein aggregation and received a lot of inquiries about our protocol to measure locomotion and how to use the FlyTracker MatLab software. This report describes a versatile locomotion measuring device and custom MatLab scripts for the extraction and analysis, and compilation of FlyTracker data in a format compatible with spreadsheet softwares. The measurement and analysis of multiple genotypes and both sexes across age shows that this method yields reproducible results that confirm that normal aging is associated with a progressive decline in locomotion as indicated by increased immobility and reduced velocity.
Window of Opportunity for Mitigation to Prevent Overflow of ICU capacity in Chicago by COVID-19
Authors: Maslov Sergei , Goldenfeld Nigel 
Published: March 2020

Executive SummaryWe estimate the growth in demand for ICU beds in Chicago during the emerging COVID-19 epidemic, using state-of-the-art computer simulations calibrated for the SARS-CoV-2 virus. The questions we address are these:Will the ICU capacity in Chicago be exceeded, and if so by how much?Can strong mitigation strategies, such as lockdown or shelter in place order, prevent the overflow of capacity?When should such strategies be implemented?Our answers are as follows:The ICU capacity may be exceeded by a large amount, probably by a factor of ten.Strong mitigation can avert this emergency situation potentially, but even that will not work if implemented too late.If the strong mitigation precedes April 1st, then the growth of COVID-19 can be controlled and the ICU capacity could be adequate. The earlier the strong mitigation is implemented, the greater the probability that it will be successful. After around April 1 2020, any strong mitigation will not avert the emergency situation. In Italy, the lockdown occurred too late and the number of deaths is still doubling every 2.3 days. It is difficult to be sure about the precise dates for this window of opportunity, due to the inherent uncertainties in computer simulation. But there is high confidence in the main conclusion that it exists and will soon be closed.Our conclusion is that, being fully cognizant of the societal trade-offs, there is a rapidly closing window of opportunity to avert a worst-case scenario in Chicago, but only with strong mitigation/lockdown implemented in the next week at the latest. If this window is missed, the epidemic will get worse and then strong mitigation/lockdown will be required after all, but it will be too late.
Deletion of calcineurin from astrocytes reproduces proteome signature of Alzheimer’s disease and epilepsy and predisposes to seizures
Authors: Tapella Laura , Dematteis Giulia , Ruffinatti Federico Alessandro , Ponzoni Luisa , Fiordaliso Fabio , Corbelli Alessandro , Albanese Enrico , Pistolato Beatrice , Pagano Jessica , Barberis Elettra , Marengo Emilio , Balducci Claudia , Forloni Gianluigi , Verpelli Chiara , Sala Carlo , Distasi Carla , Sala Mariaelvina , Genazzani Armando A. , Manfredi Marcello , Lim Dmitry 
Published: March 2020

ABSTRACTIn astrocytes, calcineurin (CaN) is involved in neuroinflammation and gliosis, while its role in healthy CNS or in early neuro-pathogenesis is poorly understood. Here we report that in astroglial CaN KO (ACN-KO) mice, at one month of age, proteome is deranged in hippocampus and cerebellum. Bioinformatic analysis reveals association with Alzheimer’s disease (AD) and epilepsy. We found significant overlap with the proteome of an AD mouse model and of human subjects with drug-resistant epilepsy. In Barnes maze ACN-KO mice learned the task but adopted serial search strategy. Strikingly, from five months of age ACN-KO mice develop spontaneous seizures with an inflammatory signature of epileptic brains. These results suggest that astroglial CaN KO impairs hippocampal connectivity, produces proteome features of neurological disorders and predisposes mice to seizures. We suggest that astroglial CaN may serve as a novel Ca2+-sensitive switch which regulates protein expression and homeostasis in the CNS.
Genes critical for development and differentiation of dopaminergic neurons are downregulated in Parkinson’s disease
Authors: Verma Aditi , Suresh Priya , Gnanabharathi Barathan , Hirsch Etienne C. , Ravindranath Vijayalakshmi 
Published: March 2020

AbstractWe performed transcriptome analysis using RNA sequencing on substantia nigra pars compacta (SNpc) from mice after acute and chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment and Parkinson’s disease (PD) patients. Acute and chronic exposure to MPTP resulted in decreased expression of genes involved in sodium channel regulation. However, upregulation of pro-inflammatory pathways was seen after single dose but not after chronic MPTP treatment. Dopamine biosynthesis and synaptic vesicle recycling pathways were downregulated in PD patients and after chronic MPTP treatment in mice. Genes essential for midbrain development and determination of dopaminergic phenotype such as, LMX1B, FOXA1, RSPO2, KLHL1, EBF3, PITX3, RGS4, ALDH1A1, RET, FOXA2, EN1, DLK1, GFRA1, LMX1A, NR4A2, GAP43, SNCA, PBX1, and GRB10 were downregulated in human PD and overexpression of LMX1B rescued MPP+induced death in SH-SY5Y neurons. Downregulation of gene ensemble involved in development and differentiation of dopaminergic neurons indicate their critical involvement in pathogenesis and progression of human PD.
CTCF Promotes Long-range Enhancer-promoter Interactions and Lineage-specific Gene Expression in Mammalian Cells
Authors: Kubo Naoki , Ishii Haruhiko , Xiong Xiong , Bianco Simona , Meitinger Franz , Hu Rong , Hocker James D. , Conte Mattia , Gorkin David , Yu Miao , Li Bin , Dixon Jesse R. , Hu Ming , Nicodemi Mario , Zhao Huimin , Ren Bing 
Published: March 2020

AbstractTopologically associating domains (TAD) and insulated neighborhoods (INs) have been proposed to constrain enhancer-promoter communications to enable cell-type specific transcription programs, but recent studies show that disruption of TADs and INs resulted in relatively mild changes in gene expression profiles. To better understand the role of chromatin architecture in dynamic enhancer-promoter contacts and lineage-specific gene expression, we have utilized the auxin-inducible degron system to acutely deplete CTCF, a key factor involved in TADs and IN formation, in mouse embryonic stem cells (mESCs) and examined chromatin architecture and gene regulation during neural differentiation. We find that while CTCF depletion leads to global weakening of TAD boundaries and loss of INs, only a minor fraction of enhancer-promoter contacts are lost, affecting a small subset of genes. The CTCF-dependent enhancer-promoter contacts tend to be long-range, spanning hundreds of kilobases, and are established directly by CTCF binding to promoters. Disruption of CTCF binding at the promoter reduces enhancer-promoter contacts and transcription, while artificial tethering of CTCF to the promoter restores the enhancer-promoter contacts and gene activation. Genome-wide analysis of CTCF binding and gene expression across multiple mouse tissues suggests that CTCF-dependent promoter-enhancer contacts may regulate expression of additional mouse genes, particularly those expressed in the brain. Our results uncover both CTCF-dependent and independent enhancer-promoter contacts, and highlight a distinct role for CTCF in promoting enhancer-promoter contacts and gene activation in addition to its insulator function.
Myocardial injury is associated with in-hospital mortality of confirmed or suspected COVID-19 in Wuhan, China: A single center retrospective cohort study
Authors: Zhang Fan , Yang Deyan , Li Jing , Gao Peng , Chen Taibo , Cheng Zhongwei , Cheng Kangan , Fang Quan , Pan Wan , Yi Chunfeng , Fan Hongru , Wu Yonghong , Li Liwei , Fang Yong , Liu Juan , Tian Guowei , He Liqun 
Published: March 2020

AbstractBackgroundSince December 2019, a cluster of coronavirus disease 2019 (COVID-19) occurred in Wuhan, Hubei Province, China and spread rapidly from China to other countries. In-hospital mortality are high in severe cases and cardiac injury characterized by elevated cardiac troponin are common among them. The mechanism of cardiac injury and the relationship between cardiac injury and in-hospital mortality remained unclear. Studies focused on cardiac injury in COVID-19 patients are scarce.ObjectivesTo investigate the association between cardiac injury and in-hospital mortality of patients with confirmed or suspected COVID-19.MethodsDemographic, clinical, treatment, and laboratory data of consecutive confirmed or suspected COVID-19 patients admitted in Wuhan No.1 Hospital from 25thDecember, 2019 to 15thFebruary, 2020 were extracted from electronic medical records and were retrospectively reviewed and analyzed. Univariate and multivariate Cox regression analysis were used to explore the risk factors associated with in-hospital death.ResultsA total of 110 patients with confirmed (n=80) or suspected (n=30) COVID-19 were screened and 48 patients (female 31.3%, mean age 70.58±13.38 year old) among them with high-sensitivity cardiac troponin I (hs-cTnI) test within 48 hours after admission were included, of whom 17 (17/48, 35.4%) died in hospital while 31 (31/48, 64.6%) were discharged or transferred to other hospital. High-sensitivity cardiac troponin I was elevated in 13 (13/48, 27.1%) patents. Multivariate Cox regression analysis showed pulse oximetry of oxygen saturation (SpO2) on admission (HR 0.704, 95% CI 0.546-0.909, per 1% decrease, p=0.007), elevated hs-cTnI (HR 10.902, 95% 1.279-92.927, p=0.029) and elevated d-dimer (HR 1.103, 95%CI 1.034-1.176, per 1mg/L increase, p=0.003) on admission were independently associated with in-hospital mortality.ConclusionsCardiac injury defined by hs-cTnI elevation and elevated d-dimer on admission were risk factors for in-hospital death, while higher SpO2could be seen as a protective factor, which could help clinicians to identify patients with adverse outcome at the early stage of COVID-19.
A microscopy-based kinetic analysis of yeast vacuolar protein sorting
Authors: Casler Jason C. , Glick Benjamin S. 
Published: March 2020

AbstractThe yeastSaccharomyces cerevisiaeis amenable to studying membrane traffic by live-cell fluorescence microscopy. We used this system to explore two aspects of cargo protein traffic through prevacuolar endosome (PVE) compartments to the vacuole. First, at what point during Golgi maturation does a biosynthetic vacuolar cargo depart from the maturing cisternae? To address this question, we modified a regulatable fluorescent secretory cargo by adding a vacuolar targeting signal. Traffic of the vacuolar cargo requires the GGA clathrin adaptors, which arrive during the early-to-late Golgi transition. Accordingly, the vacuolar cargo begins to exit the Golgi near the midpoint of maturation, significantly before exit of a secretory cargo. Second, how are cargoes delivered from PVE compartments to the vacuole? To address this question, we tracked biosynthetic and endocytic cargoes after they had accumulated in PVE compartments. The results imply that stable PVE compartments repeatedly deliver material to the vacuole by a kiss-and-run mechanism.
Dynamic Sex Chromosome Expression in Drosophila Male Germ Cells
Authors: Mahadevaraju Sharvani , Fear Justin M. , Akeju Miriam , Galletta Brian J. , Pinheiro Mara MLS. , Avelino Camila C. , Cabral-de-Mello Diogo C. , Conlon Katie , Dell’Orso Stafania , Demere Zelalem , Mansuria Kush , Mendonça Carolina A. , Palacios-Gimenez Octavio M. , Ross Eli , Savery Max , Yu Kevin , Smith Harold E. , Sartorelli Vittorio , Rusan Nasser M. , Vibranovski Maria D. , Matunis Erika , Oliver Brian 
Published: March 2020

AbstractSex chromosome gene content and expression is unusual. In many organisms the X and Y chromosomes are inactivated in spermatocytes, possibly as a defense mechanism against insertions into unpaired chromatin. In addition to current sex chromosomes, Drosophila has a small gene-poor X-chromosome relic (4th) that re-acquired autosomal status. Using single cell RNA-Seq, we demonstrate that the single X and pair of 4thchromosomes are specifically inactivated in primary spermatocytes. In contrast, genes on the single Y chromosome become maximally active in primary spermatocytes. Reduced X steady-state transcript levels are due to failed activation of RNA-Polymerase-II by phosphorylation of Serine 2 and 5.One Sentence SummarySex chromosome expression during spermatogenesis at the single cell level
Mechanisms of up-regulation of Ubiquitin-Proteasome activity in the absence of NatA dependent N-terminal acetylation
Authors: Kats Ilia , Kschonsak Marc , Khmelinskii Anton , Armbruster Laura , Ruppert Thomas , Knop Michael 
Published: March 2020

AbstractN-terminal acetylation is a prominent protein modification and inactivation of N-terminal acetyltransferases (NATs) cause protein homeostasis stress. Using multiplexed protein stability (MPS) profiling with linear ubiquitin fusions as reporters for the activity of the ubiquitin proteasome system (UPS) we observed increased UPS activity in NatA, but not NatB or NatC mutants. We find several mechanisms contributing to this behavior. First, NatA-mediated acetylation of the N-terminal ubiquitin independent degron regulates the abundance of Rpn4, the master regulator of the expression of proteasomal genes. Second, the abundance of several E3 ligases involved in degradation of UFD substrates is increased in cells lacking NatA. Finally, we identify the E3 ligase Tom1 as a novel chain elongating enzyme (E4) involved in the degradation of linear ubiquitin fusions via the formation of branched K11 and K29 ubiquitin chains, independently of the known E4 ligases involved in UFD, leading to enhanced ubiquitination of the UFD substrates.
Acute stressors experienced by layer breeders do not affect measures of stress and fear in their offspring
Authors: Peixoto Mariana R. L. V. , Karrow Niel A. , Newman Amy , Head Jessica , Widowski Tina M. 
Published: March 2020

AbstractStressors experienced by layer breeders during egg production can lead to changes in the egg hormone content, potentially impacting their offspring, the commercial layers. Genetic differences might also affect the offspring’s susceptibility to maternal experiences. In this study, we tested if maternal stress affects measures of stress and fear in five strains of layer breeders: commercial brown 1 & 2, commercial white 1 & 2 and a pure line White Leghorn. Each strain was equally separated into two groups: “Maternal Stress” (MS), where hens were subjected to a series of 8 consecutive days of acute psychological stressors, and “Control,” which received routine husbandry. Additional eggs from Control were injected either with corticosterone diluted in a vehicle solution (“CORT”) or just “Vehicle.” Stress- and fear-responses of the offspring were measured in a plasma corticosterone test and a combined human approach and novel object test. Both MS and CORT treatments failed to affect the measured endpoints in the offspring, but significant strain differences were found. The offspring of the white strains showed a higher physiological response compared to brown strains, but the White 2 offspring was consistently the least fearful strain in the behaviour tests. Our study found that the acute psychological stressors experienced by layer breeders did not affect the parameters tested in their offspring and that corticosterone does not seem to be the primary mediator of maternal stress in laying hens. This is highly important, as in poultry production, layer breeders are often subjected to short-term stressors. In addition, we successfully dissociated the physiological and behavioural parameters of stress response in laying hens, showing that increased concentrations of plasma corticosterone in response to stress is not directly associated with high levels of fear.
Mitochondrial Genome Sequence ofPhytophthora sansomeanaand Comparative Analysis ofPhytophthoraMitochondrial Genomes
Authors: Cai Guohong , Scofield Steven R. 
Published: March 2020

ABSTRACTPhytophthora sansomeanainfects soybean and causes root rot. It was recently separated from the species complexP. megasperma sensu lato.In this study, we sequenced and annotated its complete mitochondrial genome and compared it to that of nine otherPhytophthoraspecies. The genome was assembled into a circular molecule of 39,618 bp with a 22.03% G+C content. Forty-two protein coding genes, 25 tRNA genes and two rRNA genes were annotated in this genome. The protein coding genes include 14 genes in the respiratory complexes, four ATP synthetase genes, 16 ribosomal proteins genes, atatCtranslocase gene, six conserved ORFs and a uniqueorf402.The tRNA genes encode tRNAs for 19 amino acids. Comparison among mitochondrial genomes of 10Phytophthoraspecies revealed three inversions, each covering multiple genes. These genomes were conserved in gene content with few exceptions. A 3’ truncatedatp9gene was found inP. nicotianae.All 10Phytophthoraspecies, as well as other oomycetes and stramenopiles, lacked tRNA genes for threonine in their mitochondria. Phylogenomic analysis using the mitochondrial genomes supported or enhanced previous findings of the phylogeny ofPhytophthoraspp.
Antibiotic resistance genes and class 1 integron: Evidence of fecal pollution as a major driver for their abundance in water and sediments impacted by metal contamination and wastewater in the Andean region of Bolivia
Authors: Agramont Jorge , Gutierrez-Cortez Sergio , Joffré Enrique , Sjöling Åsa , Toledo Carla Calderon 
Published: March 2020

AbstractWater and sediment samples affected by mining activities were collected from three lakes in Bolivia, the pristine Andean lake Pata Khota, the Milluni Chico lake directly impacted by acid mine drainage, and the Uru-Uru lake located close to Oruro city and highly polluted by mining activities and human wastewater discharges. Physicochemical parameters, including metal compositions, were analyzed in water and sediment samples. Antibiotic resistance genes (ARGs), were screened for, and verified by quantitative PCR together with the mobile element class 1 integron (intl1) as well as crAssphage, a marker of human fecal pollution. The geneintl1showed a positive correlation withsul1, sul2, tetAandblaOXA-2. CrAssphage was only detected in Uru-Uru lake and its tributaries and significantly higher abundance of ARGs were found in these sites. Multivariate analysis showed that crAssphage abundance, electrical conductivity and pH were positively correlated with higher levels ofintl1and ARGs. Taken together our results suggest that fecal pollution is the major driver of higher ARGs andintl1in wastewater and mining contaminated environments.
Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes
Authors: Szpirer Claude 
Published: March 2020

AbstractThe rat has been used for a long time as the model of choice in several biomedical disciplines. Numerous inbred strains have been isolated, displaying a wide range of phenotypes and providing many models of human traits and diseases. Rat genome mapping and genomics was considerably developed in the last decades. The availability of these resources has stimulated numerous studies aimed at discovering disease genes by positional identification. Numerous rat genes have now been identified that underlie monogenic or complex diseases and remarkably, these results have been translated to the human in a significant proportion of cases, leading to the identification of novel human disease susceptibility genes, helping in studying the mechanisms underlying the pathological abnormalities and also suggesting new therapeutic approaches. In addition, reverse genetic tools have been developed. Several genome-editing methods were introduced to generate targeted mutations in genes the function of which could be clarified in this manner [generally these are knockout (KO) mutations]. Furthermore, even when the human gene causing a disease is identified, mutated rat strains (in particular KO strains) were created to analyze the gene function and the disease pathogenesis. Today, about 300 rat genes have been identified as underlying diseases or playing a key role in critical biological processes that are altered in diseases. This article provides the reader with an inventory of these genes.