bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human adipocyte differentiation and composition of disease-relevant lipids are regulated by miR-221-3p
Authors: Ahonen Maria A. , Asghar Muhammad Yasir , Parviainen Suvi J. , Liebisch Gerhard , Höring Marcus , Leidenius Marjut , Fischer-Posovszky Pamela , Wabitsch Martin , Mikkola Tomi S. , Törnquist Kid , Savolainen-Peltonen Hanna , Haridas P.A. Nidhina , Olkkonen Vesa M. 
Published: July 2020

AbstractMicroRNA-221-3p (miR-221-3p) is associated with both metabolic diseases and cancers. However, its role in terminal adipocyte differentiation, adipocyte lipid metabolism, and lipid signaling in human disease are uncharacterized. miR-221-3p or its inhibitor were transfected into differentiating or mature human adipocytes. Triglyceride (TG) content and adipogenic gene expression were monitored, global lipidome analysis was carried out, and mechanisms underlying the effects of miR-221-3p were investigated. Finally, cross-talk between miR-221-3p expressing adipocytes and MCF-7 breast carcinoma (BC) cells was studied, and miR-221-3p expression in tumor-proximal adipose biopsies from BC patients analyzed. miR-221-3p overexpression inhibited terminal differentiation of adipocytes, as judged from reduced TG storage and gene expression of the adipogenic markersSCD1, GLUT4, FAS, DGAT1/2, AP2, ATGLandAdipoQ. The signaling adaptor protein 14-3-3γ was identified as a potential mediator of the miR-221-3p effects. Importantly, miR-221-3p overexpression inhibitedde novolipogenesis but increased the concentrations of ceramides and sphingomyelins, while reducing diacylglycerols, concomitant with suppression of sphingomyelin phosphodiesterase, ATP citrate lyase, and acid ceramidase. miR-221-3p expression was elevated in tumor proximal adipose tissue from patients with invasive BC. Conditioned medium of miR-221-3p overexpressing adipocytes stimulated the invasion and proliferation of BC cells, while medium of the BC cells enhanced miR-221-3p expression in adipocytes. miR-221-3p plays a pivotal role in the terminal differentiation of white adipocytes and their lipid composition. Elevated miR-221-3p impairs adipocyte lipid storage and differentiation, and modifies their ceramide, sphingomyelin, and diacylglycerol content. These alterations are relevant for metabolic diseases but may also affect cancer progression.
Lateral Hypothalamic GABAergic neurons encode and potentiate sucrose’s palatability
Authors: Garcia Aketzali , Coss Alam , Luis-Islas Jorge , Puron-Sierra Liliana , Luna Monica , Villavicencio Miguel , Gutierrez Ranier 
Published: July 2020

AbstractSucrose is attractive to most species in the animal kingdom, not only because it induces a sweet taste sensation but also for its positive palatability (i.e., oromotor responses elicited by increasing sucrose concentrations). Although palatability is such an important sensory attribute, it is currently unknown which cell types encode and modulate sucrose’s palatability. Studies in mice have shown that activation of GABAergic LHAVgat+neurons evokes voracious eating; however, it is not known whether these neurons would be driving consumption by increasing palatability. Using optrode recordings, we measured sucrose’s palatability while VGAT-ChR2 transgenic mice performed a brief access sucrose test. We found a subpopulation of LHAVgat+neurons encodes palatability by increasing (or decreasing) their activity as a function of the increment in licking responses evoked by sucrose concentrations. Optogenetic gain of function experiments, where mice were able to choose among available water, 3%, or 18% sucrose solution, uncovered that opto-stimulation of LHAVgat+neurons consistently promoted higher intake of the most palatable stimulus (18% sucrose). In contrast, if they self-stimulated near the less palatable stimulus, some VGAT-ChR2 mice preferred water over 18% sucrose. Unexpectedly, activation of LHAVgat+neurons increased quinine intake but only during water deprivation, since in sated animals, they failed to promote quinine intake or tolerate an aversive stimulus. Conversely, these neurons promoted overconsumption of sucrose when it was the nearest stimulus. Also, experiments with solid foods further confirmed that these neurons increased food interaction time with the most palatable food available. We conclude that LHAVgat+neurons increase the drive to consume, but it is potentiated by the palatability and proximity of the tastant.
Stimulus-dependent contrast sensitivity asymmetries around the visual field
Authors: Himmelberg Marc M. , Winawer Jonathan , Carrasco Marisa 
Published: July 2020

AbstractAsymmetries in visual performance at isoeccentric locations are known asperformance fields. At a fixed eccentricity, visual performance is best along the horizontal, intermediate along the lower vertical, and poorest along the upper vertical meridian. Theseperformance fieldsare pervasive across a range of visual tasks, including those mediated by contrast sensitivity. However, contrastperformance fieldshave not been characterized with a systematic manipulation of stimulus spatial frequency, eccentricity, and size; three parameters that constrain contrast sensitivity. Further, individual differences inperformance fieldsmeasurements have not been assessed. Here, we use an orientation discrimination task to characterize the pattern of contrast sensitivity across four isoeccentric locations along the cardinal meridians, and to examine whether and how this asymmetry pattern changes with systematic manipulation of stimulus spatial frequency (4 cpd to 8 cpd), eccentricity (4.5° to 9°), and size (3° visual angle to 6° visual angle). Our data demonstrate that contrast sensitivity is highest along the horizontal, intermediate along the lower vertical, and poorest along the upper vertical meridian. This pattern is consistent across stimulus parameter manipulations, even though they cause profound shifts in contrast sensitivity. Eccentricity-dependent decreases in contrast sensitivity can be compensated for by scaling stimulus size alone. Moreover, we find that individual variability in the strength ofperformance fieldasymmetries is consistent across conditions. This study is the first to systematically and jointly manipulate, and compare, contrastperformance fieldsacross spatial frequency, eccentricity, and size, and to address individual variability inperformance fields.
A testis-specific Heme Peroxidase HPX12 regulates male fertility in the mosquitoAnopheles stephensi
Authors: Kumari Seena , Chauhan Charu , Rani Jyoti , Das De Tanwee , Tevatiya Sanjay , Sharma Punita , Pandey Kailash C , Pande Veena , Dixit Rajnikant 
Published: July 2020

AbstractIn humans, dysregulation of the antioxidant defense system has a detrimental impact on male fertility and reproductive physiology. Establishing such a correlation in disease vectors may pave a new way to manipulate male’s reproductive physiology, but remains the least attended. Since long - term storage of healthy and viable sperm earmarks male’s reproductive competency, we tested whether the anti-oxidative system protein also influences male fertility in the mosquitoAn. stephensi. We showed that a testis-specific HPX12 is critical for maintaining the physiological homeostasis of male mosquito’s reproductive organs. Disruption of this antioxidant enzyme by dsRNA silencing in the male mosquito severely impairs the reproductive potential of mated blood-fed female mosquitoes,resulting in a loss of 60% eggs. Our data demonstrate that increased ROS in the HPX12 mRNA depleted mosquitoes is an ultimate cause of sperm disabilities both qualitatively as well as quantitatively.
Inactivation of p21-Activated Kinase 2 (Pak2) Inhibits the Development ofNf2-Deficient Malignant Mesothelioma
Authors: Sementino Eleonora , Kadariya Yuwaraj , Cheung Mitchell , Menges Craig W. , Tan Yinfei , Kukuyan Anna-Mariya , Shrestha Ujjawal , Karchugina Sofiia , Cai Kathy Q. , Peri Suraj , Duncan James S. , Chernoff Jonathan , Testa Joseph R. 
Published: July 2020

AbstractMalignant mesotheliomas (MM) show frequent somatic loss of theNF2tumor suppressor gene. TheNF2product, Merlin, is implicated in several tumor-related pathways, including p21-activated kinase (PAK) signaling. Merlin is both a phosphorylation target for PAK and a negative regulator of this oncogenic kinase. Merlin loss results in PAK activation, and PAK inhibitors hold promise for the treatment ofNF2-deficient tumors. To test this possibility in anin vivogenetic system,Nf2f/f;Cdkn2af/fmice were crossed to mice with conditional knockout ofPak2, a highly expressed group I Pak member. Cohorts of these animals were injected in either the thoracic or peritoneal cavities with adeno-Cre virus to delete floxed alleles in the mesothelial lining. Loss ofPak2resulted in a markedly decreased incidence and delayed onset and progression of pleural and peritoneal MMs inNf2;Cdkn2a-deficient (NC)mice, as documented by Kaplan-Meier survival curves andin vivobioluminescent imaging. RNA-seq revealed that MMs fromNC;Pak2-/-mice showed downregulated expression of genes involved in several oncogenic pathways (Wnt, Akt) when compared to MMs from mice retaining Pak2. Kinome profiling showed that, as compared toNCMM cells,NC;Pak2-/-MM cells had multiple kinase changes indicative of an epithelial to mesenchymal transition. Collectively, these findings suggest thatNC;Pak2-/-MMs adapt by reprogramming their kinome and gene signature profiles to bypass the need for PAK activity via the activation of other compensatory oncogenic kinase pathways. The identification of such secondary pathways offers opportunities for rational combination therapies to circumvent resistance to anti-PAK drugs.
A secreted NlpC/P60 endopeptidase fromPhotobacterium damselaesubsp.piscicidacleaves the peptidoglycan of potentially competing bacteria
Authors: Lisboa Johnny , Pereira Cassilda , Rifflet Aline , Ayala Juan , Terceti Mateus S. , Barca Alba V. , Rodrigues Inês , Pereira Pedro J.B. , Osorio Carlos R. , García-del Portillo Francisco , Boneca Ivo Gomperts , Vale Ana do , dos Santos Nuno M.S. 
Published: July 2020

ABSTRACTPeptidoglycan(PG) is a major component of the bacterial cell wall, forming a mesh-like structure enwrapping the bacteria that is essential for maintaining structural integrity and providing support for anchoring other components of the cell envelope. PG biogenesis is highly dynamic and requires multiple enzymes, including several hydrolases that cleave glycosidic or amide bonds in the PG. Here, it is described the structural and functional characterization of an NlpC/P60-containing peptidase fromPhotobacterium damselaesubsp.piscicida(Phdp), a Gram-negative bacterium that causes high mortality of warm-water marine fish with great impact for the aquaculture industry. PnpA (PhotobacteriumNlpC-likeProteinA) has a four-domain structure with a hydrophobic and narrow access to the catalytic center and specificity for the γ-D-glutamyl-meso-diaminopimelic acid bond. However, PnpA does not cleave the PG ofPhdpand neither PG of several Gram-negative and Gram-positive bacterial species. Interestingly, it is secreted by thePhdptype II secretion system and degrades the PG ofVibrio anguillarumandV. vulnificus. This suggests that PnpA is used byPhdpto gain an advantage over bacteria that compete for the same resources or to obtain nutrients in nutrient-scarce environments. Comparison of the muropeptide composition of PG susceptible and resistant to the catalytic activity of PnpA, showed that the global content of muropeptides is similar, suggesting that susceptibility to PnpA is determined by the three-dimensional organization of the muropeptides in the PG.IMPORTANCEPeptidoglycan (PG) is a major component of the bacterial cell wall formed by long chains of two alternating sugars interconnected by short peptides, originating a mesh-like structure that enwraps the bacterial cell. Although PG provides structural integrity and support for anchoring other components of the cell envelope, it is constantly being remodeled through the action of specific enzymes that cleave or joint its components. Here, it is shown thatPhotobacterium damselaesubsp.piscicida, a bacterium that causes high mortality in warm-water marine fish, produces PnpA, an enzyme that is secreted into the environment and is able to cleave the PG of potentially competing bacteria, either for gaining competitive advantages and/or to get nutrients. The specificity of PnpA to the PG of some bacteria and its inability to cleave others may be explained by differences in the structure of the PG mesh and not by different muropeptide composition.
Positivity of SARS-CoV-2, by RT-PCR among workers of a Public Hospital in the city of Santos, SP, Brazil 2020
Authors: Caseiro Marcos Montani , Mazzurana Monica , Barreiro Bruno , Barbosa Estela Capelas , Barbosa Antônio Pires 
Published: July 2020

ABSTRACTBackgroundInfection with SARS-CoV-2, associated with severe respiratory symptoms, currently called COVID-19, represents one of the greatest health challenges of this century. Health professionals, as well as hospital workers, are the most vulnerable population for acquiring SARS-CoV-2 due to their greater proximity to sick patients, especially in specialized hospitals for the treatment of these patients.Study DesignWe ran a questionnaire by all the employees of a Public Service Hospital specialised in COVID-19 treatment (1307 employees), in the municipality of Santos, São Paulo, Brazil, who presented some symptoms compatible with COVID-19 and positive results by RT-PCR, in Oropharynx Swab collection. The questionnaire collected socio-demographic information, as well as data related to the work areas where they were divided into two groups: Employees at higher risk or those who directly deal with patients (914 employees or 69.9%) and lower risk for employees in the administrative area (393 employees or 30.1%).Results211 (16.1%) of the Hospital’s employees had to stop their work-related activities due to presenting positive RT-PCR. There were 39 (9.9%) positives in low risk areas and 172 (18.8%) positives in employees in high risk areas. Within the latter group, Nurses, Nursing Assistants and Doctors were the most frequently infected professionals. Regarding the symptoms of professionals positively diagnosed based on RT-PCR, the most frequent symptoms were body pain (83.4%); headache (80.6%); fever (57.8%) and dry cough (53.1%).ConclusionA high proportion of workers in COVID-19 specialized hospitals was infected by the virus, despite all the protective measures adopted, showing the high transmission capacity of this virus. Stricter individual protection measures among employees must be adopted.
Twitter and Census Data Analytics to Explore Socioeconomic Factors for Post-COVID-19 Reopening Sentiment
Authors: Rahman Md. Mokhlesur , Ali G. G. Md. Nawaz , Li Xue Jun , Paul Kamal Chandra , Chong Peter H.J. 
Published: July 2020

AbstractInvestigating and classifying sentiments of social media users (e.g., positive, negative) towards an item, situation, and system are very popular among the researchers. However, they rarely discuss the underlying socioeconomic factor associations for such sentiments. This study attempts to explore the factors associated with positive and negative sentiments of the people about reopening the economy, in the United States (US) amidst the COVID-19 global crisis. It takes into consideration the situational uncertainties (i.e., changes in work and travel pattern due to lockdown policies), economic downturn and associated trauma, and emotional factors such as depression. To understand the sentiment of the people about the reopening economy, Twitter data was collected, representing the 51 states including Washington DC of the US. State-wide socioeconomic characteristics of the people (e.g., education, income, family size, and employment status), built environment data (e.g., population density), and the number of COVID-19 related cases were collected and integrated with Twitter data to perform the analysis. A binary logit model was used to identify the factors that influence people toward a positive or negative sentiment. The results from the logit model demonstrate that family households, people with low education levels, people in the labor force, low-income people, and people with higher house rent are more interested in reopening the economy. In contrast, households with a high number of members and high income are less interested to reopen the economy. The accuracy of the model is good (i.e., the model can correctly classify 56.18% of the sentiments). The Pearson chi2 test indicates that overall this model has high goodness-of-fit. This study provides a clear indication to the policymakers where to allocate resources and what policy options they can undertake to improve the socioeconomic situations of the people and mitigate the impacts of pandemics in the current situation and as well as in the future.
periscope: sub-genomic RNA identification in SARS-CoV-2 Genomic Sequencing Data
Authors: Parker Matthew D , Lindsey Benjamin B , Leary Shay , Gaudieri Silvana , Chopra Abha , Wyles Matthew , Angyal Adrienn , Green Luke R , Parsons Paul , Tucker Rachel M , Brown Rebecca , Groves Danielle , Johnson Katie , Carrilero Laura , Heffer Joe , Partridge David G , Evans Cariad , Raza Mohammad , Keeley Alexander J , Smith Nikki , Filipe Ana Da Silva , Shepherd James G , Davis Chris , Bennett Sahan , Kohl Alain , Aranday-Cortes Elihu , Tong Lily , Nichols Jenna , Thomson Emma C ,   The COVID-19 Genomics UK (COG-UK) consortium, Wang Dennis , Mallal Simon , de Silva Thushan I 
Published: July 2020

AbstractWe have developed periscope, a tool for the detection and quantification of sub-genomic RNA (sgRNA) in SARS-CoV-2 genomic sequence data. The translation of the SARS-CoV-2 RNA genome for most open reading frames (ORFs) occurs via RNA intermediates termed “sub-genomic RNAs”. sgRNAs are produced through discontinuous transcription which relies on homology between transcription regulatory sequences (TRS-B) upstream of the ORF start codons and that of the TRS-L which is located in the 5’ UTR. TRS-L is immediately preceded by a leader sequence. This leader sequence is therefore found at the 5’ end of all sgRNA. We applied periscope to 1,155 SARS-CoV-2 genomes from Sheffield, UK and validated our findings using orthogonal datasets andin vitrocell systems. Using a simple local alignment to detect reads which contain the leader sequence we were able to identify and quantify reads arising from canonical and non-canonical sgRNA. We were able to detect all canonical sgRNAs at expected abundances, with the exception of ORF10. A number of recurrent non-canonical sgRNAs are detected. We show that the results are reproducible using technical replicates and determine the optimum number of reads for sgRNA analysis. In VeroE6 ACE2+/− cell lines, periscope can detect the changes in the kinetics of sgRNA in orthogonal sequencing datasets. Finally, variants found in genomic RNA are transmitted to sgRNAs with high fidelity in most cases. This tool can be applied to all sequenced COVID-19 samples worldwide to provide comprehensive analysis of SARS-CoV-2 sgRNA.
Geographic patterns of human allele frequency variation: a variant-centric perspective
Authors: Biddanda Arjun , Rice Daniel P. , Novembre John 
Published: July 2020

AbstractA key challenge in human genetics is to describe and understand the distribution of human genetic variation. Often genetic variation is described by showing relationships among populations or individuals, in each case drawing inferences over a large number of variants. Here, we present an alternative representation of human genetic variation that reveals the relative abundance of different allele frequency patterns across populations. This approach allows viewers to easily see several features of human genetic structure: (1) most variants are rare and geographically localized, (2) variants that are common in a single geographic region are more likely to be shared across the globe than to be private to that region, and (3) where two individuals differ, it is most often due to variants that are common globally, regardless of whether the individuals are from the same region or different regions. To guide interpretation of the results, we also apply the visualization to contrasting theoretical scenarios with varying levels of divergence and gene flow. Our variant-centric visualization clarifies the major geographic patterns of human variation and can be used to help correct potential misconceptions about the extent and nature of genetic differentiation among populations.
A genome epidemiological study of SARS-CoV-2 introduction into Japan
Authors: Sekizuka Tsuyoshi , Itokawa Kentaro , Hashino Masanori , Kawano-Sugaya Tetsuro , Tanaka Rina , Yatsu Koji , Ohnishi Asami , Goto Keiko , Tsukagoshi Hiroyuki , Ehara Hayato , Sadamasu Kenji , Taira Masakatsu , Shibata Shinichiro , Nomoto Ryohei , Hiroi Satoshi , Toho Miho , Shimada Tomoe , Matsui Tamano , Sunagawa Tomimasa , Kamiya Hajime , Yahata Yuichiro , Yamagishi Takuya , Suzuki Motoi , Wakita Takaji , Kuroda Makoto ,   COVID-19 Genomic Surveillance Network in Japan
Published: July 2020

AbstractBackgroundAfter the first case of COVID-19 in Japan on 15 January 2020, multiple nationwide COVID-19 clusters were identified by the end of February. The Japanese government focused on mitigating emerging COVID-19 clusters by conducting active nationwide epidemiological surveillance. However, an increasing number of cases appeared until early April, many with unclear infection routes exhibiting no recent history of travel outside Japan. We aimed to evaluate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome sequences from COVID-19 cases until early April and characterise the genealogical networks to demonstrate possible routes of spread in Japan.MethodsNasopharyngeal specimens were collected from patients and a quantitative reverse transcription polymerase chain reaction testing for SARS-CoV-2 was performed. Positive RNA samples were subjected whole genome sequencing and a haplotype network analysis was performed.FindingsSome of the primary clusters identified during January and February in Japan directly descended from Wuhan-Hu-1-related isolates in China and other distinct clusters. Clusters were almost contained until mid-March; the haplotype network analysis demonstrated that COVID-19 cases from late March through early April may have caused an additional large cluster related to the outbreak in Europe, leading to additional spread within Japan. National self-restraint during February was effective in mitigating the COVID-19 spread, but late action on stopping immigration and declaring national emergency in Japan might be involved in the later increase in cases.InterpretationGenome surveillance suggested that at least two distinct SARS-CoV-2 introductions from China and other countries occurred.FundingJapan Agency for Medical Research and Development.