bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real Time Direct Detection of β – hydroxybutyrate Production in Perfused Mice Livers Using HP DHA
Authors: Giacalone Anthony Gregory , Ragavan Mukundan , Downes Daniel , McLeod Marc , Carter Alan , Michel Keith , Bankson James A. , Merritt Matthew E. 
Published: April 2020

Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH) are increasingly prevalent in the United States. A diagnosis of NAFLD left untreated directly leads to the increase of NASH morbidity which is a result of over‐nutrition, poor diet, lack of exercise, and a sedentary lifestyle. However, NAFLD is typically reversible with a change in lifestyle. NAFLD is a group of common conditions that occur when excess fat accumulates in the liver of those who consume little alcohol. Changes in ketogenesis within the liver has been associated with NAFLD development in high‐fat diet models in mice, and in humans, lower ketogenesis is associated with an increase in hepatic steatosis. Since changes in ketogenesis are associated with different physiological conditions, it would be beneficial if the de novo ketone production can be measured in real‐time.Here, we report the detection of β‐hydroxybutyrate (BHB) in perfused liver using hyperpolarized [2‐13C] dihydroxyacetone (HP‐DHA) and Magnetic Resonance Spectroscopy (MRS). Dihydroxyacetone (DHA) is avidly taken up by the liver and rapidly phosphorylated into dihydroxyacetone phosphate (DHAP). DHAP is then metabolized into (Fig.
1) phosphoenolpyruvate (PEP), glycerol‐3‐phosphate (G3P) and glucose (in fasted mice), representing glycolysis, fatty acid synthesis, and gluconeogenesis, respectively. HP‐DHA injection does not drive BHB production by a mass action effect. Fasting mice show significantly increased ketone production, but a low alanine and lactate signal are observed as gluconeogenesis is increased. BHB is a compelling indicator of rapid flux of carbon skeletons towards ketones. Metabolism of DHA to BHB requires at least 11 steps with most of the metabolites in fasted mice not being observable. This establishes the interplay between pool size and observable HP MR Signal.The chemical shift of BHB makes it a prime target for imaging, as it does not overlap with other resonances. While previous research designs have been too complicated for clinical application, this work sets a foundation for a straightforward approach in measuring real‐time ketogenesis even as part of a routine MRI exam. This method, in particular, could serve as a powerful diagnostic tool for NAFLD and its transition to NASH.Support or Funding InformationNIH R01DK105346Sum spectra obtained by adding individual transients of the pseudo‐2D NMR acquisition post HP DHA injection. DHA and DHA‐hydrate resonances are not shown. Note dramatically increased BHB intensity in fasting. In the fasted state, 3‐ carbon precursors of glucose (alanine and lactate) show much reduced intensity.Figure 1
Construct structurally defined Low molecular Heparan Sulfate microarray and its application
Authors: Su Guowei 
Published: April 2020

Glycan microarray analysis is a high throughput method to screen the interaction between heparin oligosaccharides and target proteins. It is a powerful tool to investigate the binding between carbohydrates and carbohydrate‐binding proteins. Unlike other screening methods, microarray analysis uses a very small amount of target proteins (10 μg) to screen an entire library of Heparan Sulfate (HS) oligosaccharides. Currently we offers the microarray analysis covering up to 52 structurally defined HS oligosaccharides with a size range from pentasaccharides (5‐mer) to octodecasaccharides (18‐mer) representing many different sulfation types that can be found in nature.Support or Funding InformationNational Heart, Lung and Blood Institute, 1R01HL094463‐05National Institute of General Medical Sciences, 1U01GM1022137‐01, 1R41GM123792US FDA: U19FD004994‐01,NIH SBIR HHSN261201500019CSymbolic structures of low molecular heparan sulfate synthesized for microarrayFigure 1Workflow of Printed glycan arrays with fluorescent readout.Figure 2
Automated Analysis of Microscale Cardiac Contractile Dynamics from Intravital Multiphoton Microscopy in Mouse Ventricle
Authors: Allan-Rahill Nathaniel H. , Small David M. , Lamont Michael R. E. , Djakpa Salomon , Nishimura Nozomi 
Published: April 2020

BackgroundMultiphoton microscopy (MPM) has enabled in vivo time‐lapse imaging of the heart that shows motion of cells within the tissue with micrometer resolution. We developed automated analysis techniques to quantify cellular motion from in vivo cardiac MPM images throughout the cardiac cycle.MethodsIntravital cardiac MPM was performed on ventilated, male and female, 4–6 month‐old, C57Bl6 mice (n=9). MPM image volumes (100 μm deep) of the beating mouse left ventricle were acquired at 30 frames per second while recording the electrocardiogram and respiratory pressure (Fig.
a). Image volumes were reconstructed by assembling lines acquired nearest to a specified point in the cardio‐respiratory phase space. Bulk‐tissue motion was calculated from the three‐dimensional translational transformation that best aligned images at each point of the cardiac cycle to a reference image at the most stable portion of the cardio‐respiratory phase space (respiratory 50%, cardiac 80%). After bulk‐tissue motion was subtracted, local tissue deformation was extracted via non‐rigid registration of the reconstructed images to the reference image and divergence was calculated from the resulting vector field. Analysis methods were applied to images before and after epinephrine injection (50 μg intramuscular), and following focal sterile injury by laser irradiation (FSI).ResultsVolumes were reconstructed in 50 intervals across the cardiac cycle that show vasculature (intravenous Texas‐red dextran, red) and cardiomyocytes and leukocytes (rhodamine 6G, cyan) moving across the field of view (Fig.
b–c). Automated analysis of bulk‐tissue motion (Fig.
d–e) indicated maximum displacements occurring at 16 % (anterior‐posterior direction), 36 % (superior‐inferior) and 38 % (epi‐endocardial) of the cardiac cycle. The calculated epi‐endocardial motion amplitude correlated with stroke volume (R2=0.35) measured by echocardiography in the same animal one day before MPM imaging. Automated analysis of local tissue deformation indicated a maximum absolute deformation occurring at 10 % of the cardiac cycle (Fig.
f). Comparison to manual feature tracking across the cardiac cycle validated the automated measurements. Rigid and non‐rigid motion analysis techniques were applied to epinephrine stress test and focal sterile injury (FSI) lesion models showing, respectively, increased and decreased bulk‐tissue and local deformation and divergence.ConclusionsWe have shown and applied novel, fast, and accurate techniques for characterizing cardiac motion from in vivo cardiac MPM to study the performance of contractile cells in the heart during health and disease.Support or Funding InformationAmerican Heart Association (17POST33680127), National Institutes of Health (5R21EB024694‐03), and National Science Foundation (DBI‐1707312).Figure 1
Social interventions can lower COVID-19 deaths in middle-income countries
Authors: Paternina-Caicedo Angel , Choisy Marc , Garcia-Calavaro Christian , España Guido , Rojas-Suarez José , Dueñas Carmelo , Smith Adrian , De la Hoz-Restrepo Fernando 
Published: April 2020

Summary paragraphA novel pandemic coronavirus disease (COVID-19) was first detected in late 2019 in Wuhan (China)1,2. COVID-19 has caused 77 national governments worldwide to impose a lockdown in part or all their countries, as of April 4, 20203. The United States and the United Kingdom estimated the effectiveness of non-pharmaceutical interventions to reduce COVID-19 deaths, but there is less evidence to support choice of control measures in middle-income countries4. We used Colombia, an upper-middle income country, as a case-study to assess the effect of social interventions to suppress or mitigate the COVID-19 pandemic. Here we show that a combination of social distancing interventions, triggered by critical care admissions, can suppress and mitigate the peak of COVID-19, resulting in less critical care use, hospitalizations, and deaths. We found, through a mathematical simulation model, that a one-time social intervention may delay the number of critical care admissions and deaths related to the COVID-19 pandemic. However, a series of social interventions (social and work distance and school closures) over a period of a year can reduce the expected burden of COVID-19, however, these interventions imply long periods of lockdown. Colombia would prevent up to 97% of COVID-19 deaths using these triggered series of interventions during the first year. Our analyses could be used by decision-makers from other middle-income countries with similar demographics and contact patterns to Colombia to reduce COVID-19 critical care admissions and deaths in their jurisdictions.
Effect of emergency declaration for the COVID-19 outbreak in Tokyo, Japan in the first two weeks
Authors: Kurita Junko , Sugawara Tamie , Ohkusa Yasushi 
Published: April 2020

AbstractBackgroundJapan’s Prime Minister Abe declared an emergency to control the COVID-19 outbreak on April 7, 2020. He asked almost half of the population of Japan to reduce their personal contacts by 70–80%.ObjectThis study estimates the effectiveness of that emergency declaration. Method: We applied a simple susceptible–infected–recovery model to data of patients with symptoms in Tokyo, Japan for January 14 – April 21 as of April 22. We estimate the reproduction number in four periods: R0 before voluntary event cancellation and school closure (VECSC) which was introduced since February 27 to March 19, Rv during the VECSC, Ra after VECSC, and Re after the emergency declaration.ResultsResults suggest that the value of R0 was estimated as 1.267; its range was [1.214, 1.341]. However, Rv was estimated as 2.360 [1.844, 2.623]. Ra was estimated as 2.307 [2.035, 2.794] and Re was 0.462 [0.347, 0.514].Discussion and ConcussionOne must be reminded that these results reflect only those at two weeks after the emergency declaration. The reproduction number probably changed thereafter continuously.
Development and validation of an early warning score (EWAS) for predicting clinical deterioration in patients with coronavirus disease 2019
Authors: Guo Yabing , Liu Yingxia , Lu Jiatao , Fan Rong , Zhang Fuchun , Yin Xueru , Liu Zhihong , Zeng Qinglang , Yuan Jing , Hu Shufang , Wang Qiongya , Liao Baolin , Huang Mingxing , Yin Sichun , Zhang Xilin , Xin Rui , Lin Zhanzhou , Hu Changzheng , Zhao Boliang , He Ridong , Liang Minfeng , Zhang Zheng , Liu Li , Sun Jian , Tang Lu , Deng Lisi , Xia Jinyu , Tang Xiaoping , Liu Lei , Hou Jinlin 
Published: April 2020

AbstractBackgroundSince the pandemic outbreak of coronavirus disease 2019 (COVID-19), the health system capacity in highly endemic areas has been overwhelmed. Approaches to efficient management are urgently needed. We aimed to develop and validate a score for early prediction of clinical deterioration of COVID-19 patients.MethodsIn this retrospective multicenter cohort study, we included 1138 mild to moderate COVID-19 patients admitted to 33 hospitals in Guangdong Province from December 27, 2019 to March 4, 2020 (N =818; training cohort), as well as two hospitals in Hubei Province from January 21 to February 22, 2020 (N =320; validation cohort) in the analysis.ResultsThe 14-day cumulative incidences of clinical deterioration were 7.9% and 12.1% in the training and validation cohorts, respectively. An Early WArning Score (EWAS) (ranging from 0 to 4.5), comprising of age, underlying chronic disease, neutrophil to lymphocyte ratio, C-reactive protein, and D-dimer levels, was developed (AUROC: 0.857). By applying the EWAS, patients were categorized into low-, medium-, and high risk groups (cut-off values: two and three). The 14-day cumulative incidence of clinical deterioration in the low-risk group was 1.8%, which was significantly lower than the incidence rates in the medium-(14.4%) and high-risk (40.9%) groups (P <.001). The predictability of EWAS was similar in the validation cohort (AUROC =0.781), patients in the low-, medium-, and high-risk groups had 14-day cumulative incidences of 2.6%, 10.0%, and 25.7%, respectively (P <.001).ConclusionThe EWAS, which is based on five common parameters, can predict COVID-19-related clinical deterioration and may be a useful tool for a rapid triage and establishing a COVID-19 hierarchical management system that will greatly focus clinical management and medical resources to reduce mortality in highly endemic areas.
A nitrogen source-regulated microprotein confers an alternative mechanism of G1/S transcriptional activation in budding yeast
Authors: Tollis Sylvain , Singh Jaspal , Thattikota Yogitha , Palou Roger , Ghazal Ghada , Coulombe-Huntington Jasmin , Tang Xiaojing , Moore Susan , Blake Deborah , Bonneil Eric , Royer Catherine A. , Thibault Pierre , Tyers Mike 
Published: April 2020

AbstractCommitment to cell division at the end of G1 phase, termed Start in the budding yeastSaccharomyces cerevisiae,is strongly influenced by nutrient availability. To identify new dominant activators of Start that might operate under different nutrient conditions, we screened a genome-wide ORF overexpression library for genes that bypass a Start arrest caused by absence of the G1 cyclin Cln3 and the transcriptional activator Bck2. We recovered a hypothetical geneYLR053c,renamedNRS1for Nitrogen-Responsive Start regulator 1, which encodes a poorly characterized 108 amino acid microprotein. Endogenous Nrs1 was nuclear-localized, restricted to poor nitrogen conditions, induced upon mTORCl inhibition, and cell cycle-regulated with a peak at Start.NRS1interacted genetically withSWI4andSWI6,which encode subunits of the main G1/S transcription factor complex SBF. Correspondingly, Nrs1 physically interacted with Swi4 and Swi6 and was localized to G1/S promoter DNA. Nrs1 exhibited inherent transactivation activity and fusion of Nrs1 to the SBF inhibitor Whi5 was sufficient to suppress other Start defects. Nrs1 appears to be a recently evolved microprotein that rewires the G1/S transcriptional machinery under poor nitrogeny conditions.Author SummarUnicellular microorganisms must adapt to ever-changing nutrient conditions and hence must adjust cell growth and proliferation to maximize fitness. In the budding yeastSaccharomyces cerevisiae, commitment to cell division, termed Start, is heavily influenced by nutrient availability. Our understanding of how Start is activated is based mainly on experiments carried out under rich nutrient conditions. To identify potential new Start regulators specific to poor nutrient environments, we screened for genes able to bypass a genetic Start arrest caused by loss of the G1 cyclin Cln3 and the transcriptional activator Bck2. This screen uncoveredYLR053c, which we renamedNRS1for Nitrogen-Responsive Start regulator. Sequence analysis across yeast species indicated that Nrs1 is a recently-evolved microprotein. We showed thatNRS1is nutrient- and cell cycle-regulated, and directly binds the main G1/S transcription factor complex SBF. We demonstrated that Nrs1 has an intrinsic trans-activation activity and provided genetic evidence to suggest that Nrs1 can bypass the requirement for normal Cln3-dependent activation of G1/S transcription. These results uncover a new mechanism of Start activation and illustrate how microproteins can rapidly emerge to rewire fundamental cellular processes.
Neural correlates of cognitive motor signals in primary somatosensory cortex
Authors: Jafari Matiar , Aflalo Tyson NS , Chivukula Srinivas , Kellis Spencer S , Salas Michelle Armenta , Norman Sumner L , Pejsa Kelsie , Liu Charles Y. , Andersen Richard A 
Published: April 2020

AbstractClassical systems neuroscience positions primary sensory areas as early feed-forward processing stations for refining incoming sensory information. This view may oversimplify their role given extensive bi-directional connectivity with multimodal cortical and subcortical regions. Here we show that single units in human primary somatosensory cortex encode imagined reaches centered on imagined limb positions in a cognitive motor task. This result suggests a broader role of primary somatosensory cortex in cortical function than previously demonstrated.
Interactions between fungal hyaluronic acid and host CD44 promote internalization by recruiting host autophagy proteins to forming phagosomes
Authors: Ding Sheng Li , Pandey Aseem , Feng Xuehuan , Yang Jing , da Costa Luciana Fachini , Mouneimne Roula , Rice-Ficht Allison , Bell Samantha L. , Watson Robert O. , Patrick Kristin , Qin Qing-Ming , Ficht Thomas A. , de Figueiredo Paul 
Published: April 2020

SummaryPhagocytosis and autophagy play critical roles in immune defense.Cryptococcus neoformans(Cn), a fungal pathogen that causes fatal infection, subverts the host autophagy initiation complex (AIC) and its upstream regulatory proteins, to promote its phagocytosis and intracellular parasitism of host cells. The mechanisms by which the pathogen engages host AIC proteins remain obscure. Here, we show that the recruitment of host AIC proteins to forming phagosomes is dependent upon the activity of CD44, a host cell surface receptor that engages fungal hyaluronic acid (HA). This interaction elevates intracellular Ca2+concentrations and activates CaMKKβ and its downstream target AMPKα, which results in activation of ULK1 and the recruitment of AIC components. Moreover, we demonstrate that HA-coated beads efficiently recruit AIC components to phagosomes. Taken together, these findings show that fungal HA plays a critical role in directing the internalization and productive intracellular membrane trafficking of a fungal pathogen of global importance.Graphical AbstractIn BriefDing et al. reveal that interactions between fungal hyaluronic acid (HA) and host CD44 activate a Ca2+- CaMKKβ-AMPK-ULK1 signaling pathway that recruits autophagy initiation complex components to forming phagosomes to drive fungal internalization.HighlightsFungal HA interactions with host cells drive a novel non-canonical, ligand-induced, autophagy pathway in phagocytic cellsCryptococcus neoformansrecruits host CD44, together with AIC components and regulatory proteins, to forming phagocytic cups to initiate host cell internalizationFungal HA interactions with CD44 on host cell surfaces elevate intracellular Ca2+concentrations, leading to activation of CaMKKβA Ca2+-CaMKKβ-AMPK-ULK1 signaling axis is involved in HA and CD44 induced autophagy protein recruitment during Cn internalization
Interplay of host regulatory network on SARS-CoV-2 binding and replication machinery
Authors: Ahmed Shiek SSJ , Paramasivam Prabu , Raj Kamal , Kumar Vishal , murugesan Ram , Ramakrishnan  
Published: April 2020

AbstractWe dissect the mechanism of SARS-CoV-2 in human lung host from the initial phase of receptor binding to viral replication machinery. We constructed two independent lung protein interactome to reveal the signaling process on receptor activation and host protein hijacking machinery in the pathogenesis of virus. Further, we test the functional role of the hubs derived from both interactome. Most hubs proteins were differentially regulated on SARS-CoV-2 infection. Also, the proteins of viral replication hubs were related with cardiovascular disease, diabetes and hypertension confirming the vulnerability and severity of infection in the risk individual. Additionally, the hub proteins were closely linked with other viral infection, including MERS and HCoVs which suggest similar infection pattern in SARS-CoV-2. We identified five interconnecting cascades between hubs of both networks that show the preparation of optimal environment in the host for viral replication process upon receptor attachment. Interestingly, we propose that seven potential miRNAs, targeting the intermediate phase that connects receptor and viral replication process a better choice as a drug for SARS-CoV-2.
Grapevine pruning time affects natural wound colonization by wood-invading fungi
Authors: del Pilar Martínez-Diz María , Eichmeier Ales , Spetik Milan , Bujanda Rebeca , Díaz-Fernández Ángela , Díaz-Losada Emilia , Gramaje David 
Published: April 2020

ABSTRACTGrapevine pruning wounds made during the dormant season are a port of entry of wood-invading fungi. Timing of pruning may affect the wound susceptibility to these fungi, such as those associated with grapevine trunk diseases (GTDs). This study aimed to determine the effect of pruning time on natural fungal infection in six vineyards in Galicia, Spain, belonging to three Denominations of Origin (D.O) over two growing seasons. Pruning wounds were left unprotected physically and chemically during two periods of three months each, from November to February and from February to May. The diversity and composition of the fungal microbiome that colonized the pruning wounds was identified by ITS2 high-throughput amplicon sequencing (HTAS). A broad range of fungi was able to colonize grapevine pruning wounds at both infection periods. Fungal microbiome composition did not shift as year of sampling. Fungal communities were affected in their diversity and composition by the D.O., whereas the spatial variation (i.e. vineyard within each region) was low. Pruned canes harboured a core community of fungal species, which appeared to be independent of the infection period. Accumulated rainfall over 8 and 11 weeks after pruning positively correlated with the total fungal microbiome and in particular with the GTD fungal genusDiaportheabundances. A strong seasonal effect on GTD fungal infection was detected for most genera, with higher percentages of abundance detected after pruning in February (winter) as compared with that of pruning in November (mid-autumn). In light of the GTD colonization results and given the environmental conditions and the geographical location of this study, early pruning is recommended to reduce the infections caused by GTD fungi during the pruning season in Galicia.