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Cystic Fibrosis Transmembrane Regulator Correction Attenuates Heart Failure-Induced L...
Franziska Uhl
Lotte Vanherle

Franziska Uhl

and 2 more

October 16, 2021
Background and Purpose: Heart failure (HF) affects 64 million people worldwide. Despite advancements in prevention and therapy, quality of life remains poor for many HF patients due to target organ damage. Pulmonary manifestations of HF are well-established. However, difficulties in the treatment of HF patients with chronic lung phenotypes remain, as standard therapies are often complicated by contraindications. Here, we verify the downregulation of the cystic fibrosis transmembrane regulator (CFTR) in the HF lung, a concept that may provide new mechanism-based therapies for HF patients with pulmonary complications. Experimental Approach: Ligation of the left anterior descending coronary artery in mice was used to induce myocardial infarction (MI). At 10 weeks post-MI, pharmacological CFTR corrector therapy (Lumacaftor (Lum)) was applied systemically or lung-specific for 2 weeks, and the lungs were analysed using histology, flow cytometry, Western blotting, and qPCR. Key Results: Experimental HF associated with an apparent lung phenotype characterized by reduction of pulmonary CFTR+ cells, vascular remodelling, and pronounced tissue inflammation as evidenced by infiltration of pro-inflammatory monocytes and elevation of classically-activated macrophages in the lung. PharmacologicalCFTR correction with Lum mitigated the HF-induced downregulation of pulmonary CFTR expression, increased the proportion of CFTR+ cells in the lung, and diminished the HF-associated elevation of classically-activated non-alveolar macrophages within the lungs with implication for vessel wall thickness. Conclusion and Implications: Collectively, our data suggest that pharmacological CFTR correction possesses the capacity to alleviate HF-induced inflammation in the lung and may emerge as treatment option for HF patients with chronic lung phenotypes.
Large paracetamol overdose -- higher dose NAC is required - CON
Ruben Thanacoody

Ruben Thanacoody

October 16, 2021
Paracetamol overdose is common in developed countries but less than 10% involve large ingestions exceeding 30g or 500mg/kg. High dose acetylcysteine (NAC) has been proposed in patients taking large paracetamol overdoses based on reports of hepatotoxicity despite early initiation of NAC treatment with the commonly used 300 mg/kg intravenous acetylcysteine regimen. The evidence from cohorts of patients treated with the standard NAC regimen after large paracetamol overdoses shows that it is effective in most patients. Small studies in patients whose paracetamol concentration are above the 300mg/L nomogram line show that modification of the standard NAC regimen to provide a total of 400-500 mg/kg NAC over 21-22h may reduce the risk of hepatotoxicity (peak ALT>1000 IU/L) but the impact on development of hepatic failure, liver transplantation and mortality with this approach is presently unknown. Better risk stratification of patients taking paracetamol overdose may allow higher dose NAC and adjunctive treatments such as CYP2E1 inhibition and extracorporeal removal of paracetamol to be targeted to those patients at the highest risk of hepatotoxicity after a large paracetamol overdose.
Acute administration of Baclofen after spinal cord injury improves locomotor behavior...
Nídia de Sousa
Andreia  Pinho

Nídia de Sousa

and 9 more

October 16, 2021
Spinal cord injury (SCI) leads to severe motor and sensory functional impairments that affect personal and social behaviors. With no effective treatment, deficits in motor function are the most visible consequence of SCI. However, other complications produce a significant impact on SCI patient’s welfare. Spasticity is a neurological impairment that affects the control of muscle tone as a consequence of an insult in the central nervous system (e.g., SCI). Baclofen, a GABA agonist, is the most effective drug for spasticity treatment. This drug activates GABAB receptors decreasing the neurotransmitters release and neuronal hyperpolarization, which results in spasticity relief. Interestingly, emerging data reveals that Baclofen can also play a role on neuroprotection and regeneration after SCI. Our goal is to highlight the role of Baclofen as a potential treatment to promote recovery from SCI. We used a compression SCI mouse model with the administration of Baclofen at different time-points after injury. Our data showed that Baclofen is more effective when a single dose is administered acutely, leading to locomotor improvements in mice. Moreover, Baclofen administration also led to improved bladder function control in all experimental groups. Interestingly, acute Baclofen administration modulates microglia activation state and levels of circulating cytokines, suggesting a role of Baclofen in the modulation of the immune response. Although deeper studies must be performed to understand the cellular/molecular mechanisms that underlie the functional improvements produced by Baclofen, our data shed light into the pharmacological potential of Baclofen to promote recovery in a SCI context.
An SVEICRD model for assessing the impact of the lock-down intervention and vaccinati...
Idil Aydin
Aysun Bozanta

Idil Aydin

and 3 more

October 16, 2021
In this research, we aim to forecast the trajectory of the COVID-19 pandemic in terms of the number of exposed, infected, vaccinated, hospitalized, recovered, and dead people, and observe the effects of different vaccination strategies on the spread of the COVID-19. We simulate the ongoing trajectory of the outbreak in three countries, namely, Canada, the UK, and Israel using the susceptible - vaccinated - exposed - infected - critical - recovered - dead (SVEICRD) model. We consider two vaccination strategies and investigate their effects on the number of exposed and death cases. We perform an extensive numerical study to assess the implications of different strategies and spread scenarios. Our findings confirm that the fourth wave has begun in all three countries, and already reached its peak. We observe that starting second dose vaccination as early as possible is the most effective in mitigating the spread of COVID-19, although it does require more vaccination supply than the alternative strategies. Our results show that the SVEICRD model successfully forecasts the changing number of people in each compartment and the vaccination strategy significantly impacts the trajectory of the outbreak.
A left bundle branch block morphology tachycardia with fragmented potentials at the H...
Masahiro Toba
Toshihiro Nasu

Masahiro Toba

and 5 more

October 15, 2021
A left bundle branch block morphology tachycardia with fragmented potentials at the His bundle area Masahiro Toba, MDa, Toshihiro Nasu, CEb, Nobuyoshi Nekomiya, CEb, Ryo Itasaka, CEb, Takao Makino, MDa, Hisashi Yokoshiki, MD, PhDaaDepartment of Cardiovascular Medicine, Sapporo City General Hospital, Sapporo, JapanbDivision of Medical Engineering Center, Sapporo City General Hospital, Sapporo, JapanAddress for correspondence :Hisashi Yokoshiki MD, PhDE-mail:hisashi.yokoshiki@doc.city.sapporo.jpDepartment of Cardiovascular Medicine Sapporo City General Hospital, Kita-11, Nishi-13, Chuo-ku, Sapporo 060-8604, Japan.Phone: 81-11-726-2211Fax: 81-11-726-7912Key words : longitudinal dissociated his bundle, left bundle branch block morphology tachycardia, fragmented potentials, radiofrequency ablation
Biological and physiological properties of reverse ankyrin engineered for dimer const...
On-anong Juntit
Umpa Yasamut

On-anong Juntit

and 12 more

October 15, 2021
Assembly and budding in the late-stage of human immunodeficiency virus type 1 (HIV-1) production relies on the polymerization of Gag protein at the inner leaflet of the plasma membrane. We previously generated an ankyrin repeat protein (Ank1D4) that specifically interacts with the CAp24 protein. This study aimed to improve the binding activity of Ank1D4 by generating two platforms for the Ank1D4 dimer. The design of these constructs featured a distinct orientation of monomeric Ank1D4 connected by a linker peptide (G 4S) 4. The binding surfaces in either dimer generated from the C-terminus of the Ank1D4 monomer linked with the N-terminus of another monomer (Ank1D4 NC-NC) or its inverted form (Ank1D4 NC-CN), similar to monomeric Ank1D4. The interaction of Ank1D4 NC-CN with CAp24 from capture ELISA was significantly greater than that of Ank1D4 NC-NC and the parental Ank1D4. The bifunctional characteristic of Ank1D4 NC-CN was further demonstrated using sandwich ELISA. The binding kinetics of these ankyrins were evaluated using bio-layer interferometry analysis. The K D of Ank1D4 NC-CN, Ank1D4 NC-NC and monomeric Ank1D4 was 3.5 nM, 53.7 nM, and 126.2 nM, respectively. The dynamics of the interdomain linker and the behavior of ankyrin dimers were investigated in silico. Upon the binding distance calculation from the candidate structures, the achievement in obtaining double active sites is more possible in Ank1D4 NC-CN. The CD spectroscopic data indicated that secondary structure of dimer forms resemble Ank1D4 monomer α-helical content. This finding confers the strategy to generate dimer from rigid scaffold for acquiring the binding avidity.
Intraspecific independent evolution of floral spur length in response to local flower...
Tsubasa Toji
Shun Hirota

Tsubasa Toji

and 4 more

October 15, 2021
Geographic differences in floral traits may reflect geographic differences in effective pollinator assemblages. Independent local adaptation to pollinator assemblages in multiple regions would be expected to cause parallel floral trait evolution, although sufficient evidence for this is still lacking. In this study, we investigated the relationship between flower spur length and pollinator size in 16 populations of Aquilegia buergeriana var. buergeriana distributed in four mountain regions in the Japanese Alps. We also examined the genetic relationship between yellow- and red-flowered individuals, to see if color differences caused genetic differentiation by pollinator isolation. Genetic relationships among 16 populations were analyzed based on genome-wide single-nucleotide polymorphisms. Even among populations within the same mountain region, pollinator size varied widely, and the average spur length of A. buergeriana var. buergeriana in each population was strongly related to the average visitor size of that population. Genetic relatedness between populations was not related to the similarity of spur length between populations; rather, it was related to the geographic proximity of populations in each mountain region. Our results indicate that spur length in each population evolved independently of the population genetic structure but in parallel in different mountain regions. Further, yellow- and red-flowered individuals of A. buergeriana var. buergeriana were not genetically differentiated. Unlike other Aquilegia species in Europe and America visited by hummingbirds and hawkmoths, this species is consistently visited by bumblebees in Japan. As a result, genetic isolation by flower color has not occurred.
Ground-nesting by arboreal American robins (Turdus migratorius)
Sarah  Winnicki
Mark Hauber

Sarah Winnicki

and 3 more

October 15, 2021
Animals with dependent and vulnerable young need to decide where to raise their offspring to minimize ill effects of weather, competition, parasitism, and predation. These decisions have critical fitness consequences through impacting the survival of both adults and juveniles. Birds routinely place their nest in specific sites, allowing species to be broadly classified based on nest location (e.g., ground- or tree-nesting). However, from 2018–2020 we observed 24 American robin (Turdus migratorius) nests placed not on their species-typical arboreal substrates or human-made structures but on the ground at a predator-rich commercial arbor in Illinois, U.S.A. This behavior does not appear to be in response to competition and did not affect nest daily survival rate but was restricted to the early half of the breeding season. We hypothesize that ground-nesting may be an adaptive response to avoid exposure and colder temperatures at sites above the ground early in the breeding season or a non-adaptive consequence of latent robin nest-placement flexibility.
Brain Mineralocorticoid receptor in health and disease: from molecular signaling to c...
Susana Paul
Katja Wingenfeld

Susana Paul

and 3 more

October 15, 2021
Brain mineralocorticoid receptors (MR) mediate effects of aldosterone in relation to salt homeostasis, and of glucocorticoid stress hormones corticosteroids in the context of stress adaptation. Brain stem MRs respond to aldosterone, while forebrain MRs mediate rapid and delayed MR-mediated glucocorticoids effects in conjunction with the glucocorticoid receptor. MR-mediated effects depend on gender, genetic variations and environmental influences. Disturbed MR activity by chronic stress or in certain (endocrine) diseases can cause deleterious effects on affective state, cognitive and behavioural function in susceptible individuals. High MR activation may have protective effects in healthy individuals, whereas dysregulated high MR activity during a stress response would require treatment with mineralocorticoid receptor antagonists (MRAs). Here, we discuss recent pharmacological and genetic developments, from the molecular underpinnings of MR signaling and function, to pharmacological interventions in the clinic. Improved understanding of MR dependent pathways will help to improve glucocorticoid therapy, unwanted side effects and psychiatric symptoms.
Best practices in metabarcoding of fungi: from experimental design to results
Leho Tedersoo
Mohammad Bahram

Leho Tedersoo

and 7 more

October 15, 2021
The development of high-throughput sequencing (HTS) technologies has greatly improved our capacity to identify fungi and unveil their ecological roles across a variety of ecosystems. Here we provide an overview about current best practices in metabarcoding analysis of fungal communities, from experimental design through molecular and computational analyses. By re-analysing published datasets, we find that operational taxonomic units (OTUs) outperform amplified sequence variants (ASVs) in recovering fungal diversity, which is particularly evident for long markers. Additionally, analysis of the full-length ITS region allows more accurate taxonomic placement of fungi and other eukaryotes compared with the ITS2 subregion. We conclude that metabarcoding analyses of fungi are especially promising for co-analyses with the functional metagenomic or transcriptomic data, integrating fungi in the entire microbiome, recovery of novel fungal lineages and ancient organisms as well as barcoding of old specimens including type material.
A Subject-Transfer Framework for Obviating Inter- and Intra- Subject Variability in E...
Valentin Chiffard

Valentin Chiffard

November 08, 2021
1- IntroductionL’article que nous allons étudier est intitulé "A Subject-Transfer Framework for Obviating Inter- and Intra- Subject Variability in EEG-Based Drowsiness Detection" \cite{Wei2018}. Dans le cadre de la détection de la somnolence par un électroencéphalogramme, cet article présente une nouvelle approche d'apprentissage par transfert permettant de « réduire le temps de calibration pour un nouvel utilisateur de 90% (18,00 min à 1,72±0,36min) sans compromettre les performances »\cite{Wei2018}. Cet article est paru le 01 juillet 2018 dans la revue scientifique NeuroImage (volume 174, pages 407-419). Cette revue publiée par Elsevier Science est spécialisée dans le domaine de la neuroimagerie. Les contributeurs de l’article étudié sont : Chun-Shu Wei, doctorant du département de bioingénierie de l’université de Californie San Diego aux États-Unis lors de l'écriture de l'article, actuellement professeur agrégé dans le Departement of computeur science de l'Univérsité nationale Yang Ming Chiao Tung. (Lien bio)Yuan-Pin Lin, professeur agrégé à l’Institut des Sciences Médicale et Technologique de l’Université nationale Sun Yat-sen à Taïwan. (Lien bio) Yu-Te Wang, doctorant du département de bioingénierie de l’université de Californie San Diego aux États-Unis lors de l'écriture de l'article, actuellement chercheur dans le domaine des Brain Computeur Interface chez Microsoft. (Lien bio)Chin-Teng Lin, professeur agrégé à l’Institut de l’Intelligence Artificielle à l’université de Technologie à Sydney en Australie. (Lien bio)Tzyy-Ping Jung, professeur agrégé du département de bioingénierie de l’université de Californie San Diego aux États-Unis. (Lien bio) Dans un premier temps, nous allons présenter le contexte dans lequel l’article s’inscrit. Dans un second temps, nous étudierons les différents travaux réalisés sur le sujet abordé par l’article, puis nous présenterons les contributions de ce dernier. Après avoir expliqué les différentes expériences et les différents résultats obtenus, nous conclurons sur cet article. 2- Contexte de l'article Les BCI (Brain Computer Interface) enregistrent des signaux émis par le cerveau et les « traduits sous forme de message ou de commande pour certaines tâches interactives »  \cite{2016}.
A coupled dynamic leakage loss and flood routing model for ephemeral rivers with comp...
Congmin Liu
Chengzhong Pan

Congmin Liu

and 4 more

October 15, 2021
Ephemeral rivers commonly occur in regions with a shortage of water resources, and their channel configuration tends to change substantially owing to cultivation, tree planting and sand extraction. There is an urgent need to restore degraded river ecosystems. During short-term water conveyance, water storage in sand pits and leakage in dry riverbeds retards the flow of water, which is detrimental for ecological restoration of the riparian zone. A coupled dynamic leakage loss and flood routing model was established to predict the flow processes in the complex river channel of the Yongding River in China. The model mainly included three sub-models of flow dynamics, dynamic leakage loss, and water balance along multiple cross sections of the river channel. The complex section is reflected in the different infiltration properties for each section, and the existence of sand pits. The water head was dominated by flow velocity and the overflow from sand pits. Owing to the difference in landforms and the deposited sediment size of the riverbed bottom, the river channel was divided into 11 cross sections and a sand pit to ascertain the respective infiltration or leakage loss processes. The input parameters of the model came from field surveys of sand pits, river geometry and hydrogeology. The model was also calibrated and validated using monitoring data from ecological water releases into the Yongding River in 2019 and 2020. This coupled model can predict the water leakage loss and flow process of the water head and also provide important guidance for river reconstruction and ecological restoration.
On the importance of monsoon rainstorm impact period in soil salinization
Zengming Ke
Xiaoli Liu

Zengming Ke

and 6 more

October 15, 2021
Abstract: Long-term soil salt accumulation could lead to salinization. Aimed to prevent soil salinization, we investigated soil salt dynamics, its interface with the groundwater table, rainfalls duration and the impact periods when salt is mostly accumulated. Total soil salt accumulation and dynamic distribution were monitored in the 0–80 cm layer in alluvial farmland from 2018 to 2020. We found soil salt contents increased by 0.15 g kg–1 and 0.07 g kg–1 in the 0–40 and 40–80 cm soil layers, respectively, which indicated that soil salinization occurred. We defined the rainstorm impact period (RIP) as period when soil salt dynamic distribution was affected by rainstorm event. The salinity time-trend during RIP was sequentially characterized by a first salt leaching, followed by a rapid and then slow salt accumulation, which took the first 4 days, from day 4 to 10, and then beyond, respectively. In the first leaching stage, salt migration content was determined by rainfall (P < 0.05) which could leach 41.5% of salt on average in the whole soil layer. In the rapid accumulation stage, lots of salt accumulated due to high evapotranspiration and shallow groundwater table. In the slow accumulation stage, salt accumulation rate was inhibited by deeper groundwater table. In addition, the total accumulated soil salt in the whole soil layer increased by 0.14 g kg–1 in the RIPs, which comprised only 14.5% of the overall study period, but the value accounted for 63.6% of the salt accumulation, thereby indicating that RIPs were the main periods when salt accumulated during the soil salinization process. Our results provided insights into soil salt dynamic distribution during RIPs, thereby facilitating the effective prevention and control of soil salinization.
Estimation of subsurface flow from high-resolution temperature profiles
Bo Zhang
Kai Gu

Bo Zhang

and 6 more

October 15, 2021
Subsurface flow rates are critical for hydrology and geothermal research, while field characterization remains a challenge. There are several analytical solutions for calculating the vertical water flux based on measured temperatures. Heat is a popular natural tracer to estimate subsurface flow rates. However, quantifying flow rates is impeded by insufficient sensors spacing during field investigations or simplifying assumptions for analysis such as sinusoidal temperature boundary. The objective of this study is to develop a convenient method to investigate subsurface flow on the sub-meter scale. Here, we present a program to estimate water fluxes based on temperature-depth profiles, so-called TempFlow. TempFlow is a numerical program written in MATLAB that calculates steady state flow in transient heat tracing based on the inversion of measured high-resolution temperature-depth series observed at a certain time. In this program, the Fiber Optic Distributed Temperature Sensing (FO-DTS) is recommended for temperature collection. FO-DTS techniques provide high-resolution temperature measurements with continuous temperature profiles that account for sub-meter scale and nonperiodic boundary conditions in saturated sediments. The estimated subsurface flow using TempFlow was validated in a medium-scale tank with a series of experiments, where the hydraulic and temperature boundary conditions were well-controlled. The results indicate that the estimation using TempFlow obtained similar results as the experiments. Thus, the method could potentially be used to determine the flow rate of the subsurface.
Advancing Remote Sensing and Machine Learning-Driven Frameworks for Groundwater Withd...
Sayantan Majumdar
Ryan Smith

Sayantan Majumdar

and 3 more

October 15, 2021
Groundwater plays a crucial role in sustaining global food security but is being over-exploited in many basins of the world. Despite its importance and finite availability, local-scale monitoring of groundwater withdrawals required for sustainable water management practices is not carried out in most countries, including the United States. In this study, we combine publicly available datasets into a machine learning framework for estimating groundwater withdrawals over the state of Arizona. Here we include evapotranspiration, precipitation, crop coefficients, land use, well density, and watershed stress metrics for our predictions. We employ random forests to predict groundwater withdrawals from 2002-2020 at a 2 km spatial resolution using in-situ groundwater withdrawal data available for Arizona Active Management Areas (AMA) and Irrigation Non-Expansion Areas (INA) from 2002-2009 for training and 2010-2020 for validating the model respectively. The results show high training (R2≈ 0.86) and good testing (R2≈ 0.69) scores with normalized mean absolute error (NMAE) ≈ 0.64 and normalized root mean square error (NRMSE) ≈ 2.36 for the AMA/INA region. Using this method, we spatially extrapolate the existing groundwater withdrawal estimates to the entire state and observe the co-occurrence of both groundwater withdrawals and land subsidence in South-Central and Southern Arizona. Our model predicts groundwater withdrawals in regions where production wells are present on agricultural lands and subsidence is observed from Interferometric Synthetic Aperture Radar (InSAR), but withdrawals are not monitored. By performing a comparative analysis over these regions using the predicted groundwater withdrawals and InSAR-based land subsidence estimates, we observe a varying degree of subsidence for similar volumes of withdrawals in different basins. The performance of our model on validation datasets and its favorable comparison with independent water use proxies such as InSAR demonstrate the effectiveness and extensibility of our combined remote sensing and machine learning-based approach.
Whole genome resequencing reveals signatures of rapid selection in a virus affected c...
Owen Holland
Madeline Toomey

Owen Holland

and 6 more

October 15, 2021
Infectious diseases are recognised as one of the greatest global threats to biodiversity and ecosystem functioning. Consequently, there is a growing urgency to understand the speed at which adaptive phenotypes can evolve and spread in natural populations to inform future management. Here we provide evidence of rapid genomic changes in wild Australian blacklip abalone (Haliotis rubra) following a major population crash associated with an infectious disease. A genome wide association study on H. rubra was conducted using pooled whole genome re-sequencing data from commercial fishing stocks varying in historical exposure to haliotid herpesvirus-1 (HaHV-1). Approximately 25,000 SNP loci associated with virus exposure were identified, many of which mapped to genes known to contribute to HaHV-1 immunity in the New Zealand pāua (H. iris) and herpesvirus response pathways in haliotids and other animal systems. These findings indicate genetic changes across a single generation in H. rubra fishing stocks decimated by HaHV-1, with stock recovery determined by rapid evolutionary changes leading to virus resistance. This is a novel example of rapid adaptation in natural populations of a non-model marine organism, highlighting the pace at which selection can potentially act to counter disease in wildlife communities.
Pollinator guilds respond contrastingly at different scales to landscape parameters o...
Kolja Bergholz
Lara-Pauline Sittel

Kolja Bergholz

and 4 more

October 15, 2021
Land-use intensification is the main factor for the catastrophic decline of insect pollinators. However, land-use intensification includes multiple processes that act across various scales and should affect pollinator guilds differently depending on their ecology. We aimed to reveal how two main pollinator guilds, wild bees (specialists) and hoverflies (generalists), respond to different land-use intensification measures, i.e. arable field cover (AFC), landscape heterogeneity (LH) and functional flower composition of local plant communities as a measure of habitat quality. We sampled wild bees and hoverflies on 22 dry grassland sites within a highly intensified landscape (NE Germany) within three campaigns using pan traps. We estimated AFC and LH on consecutive radii (60-3000m) around the dry grassland sites and estimated the local functional flower composition. Wild bee species richness and abundance was positively affected by LH and negatively by AFC at small scales (140-400m). In contrast, hoverflies were positively affected by AFC and negatively by LH at larger scales (500-3000m), where both landscape parameters were negatively correlated to each other. At small spatial scales, though, LH had a positive effect on hoverflies abundance. Functional flower diversity had no positive effect on pollinators, but conspicuous flowers seem to attract abundance of both guilds. In conclusion, landscape parameters contrarily affect two pollinator guilds at different scales. The correlation of landscape parameters may influence the observed relationships between landscape parameters and pollinators. Hence, effects of land-use intensification seems to be highly landscape-specific.
Association between Reduced estimated Glomerular Filtration Rate and Cardiac Structur...
Liying Mu
Lu Chen

Liying Mu

and 6 more

October 15, 2021
Objectives To investigate the relationship between small reductions in estimated glomerular filtration rate (eGFR) and cardiac structure and function in patients with essential hypertension. Methods The study group included 565 patients with essential hypertensive. eGFR was calculated by EPI equation and cardiac structure and function were assessed using echocardiography. The participants were divided into three groups: eGFR ≥90 mL/min /1.73 m2, 60-89 mL/min/1.73 m2, and 30-59 mL/min /1.73 m2. Pearson correlation analysis and multiple stepwise linear regression analysis were performed to evaluate associations between eGFR and echocardiogram parameters. Results Compared with patients with eGFR ≥ 90 mL/min/ 1.73 m2, those with eGFR 60-89 mL/min/ 1.73 m2 and 30-59 mL/min/ 1.73 m2 had higher left ventricular end-diastolic diameter (LVEDD) (p=0.019), mitral valve E wave (p=0.004), left atrial diameter (LAD) (p=0.001), right atrial diameter (RAD) (p=0.001), right ventricular diameter (RVD) (p=0.001) and lower left ventricular ejection fraction (LVEF) (p=0.01). After further adjustment for traditional cardiovascular risk factors including systolic and diastolic blood pressure, BMI, diabetes, dyslipidemia and smoking, eGFR was still associated with LVEF (p<0.001), LAD (p<0.001) and RAD (p=0.003). Conclusion Among patients with essential hypertension, even mildly reduced renal function is independently associated with greater cardiac remodeling, indicated by left atrial and right atrial enlargement, and worse left ventricular systolic function.
Global identification of full-length cassava lncRNAs unveils the role of CRIR1 in col...
shuxia li
Zhihao Cheng

shuxia li

and 9 more

October 15, 2021
Long non-coding RNAs (lncRNAs) have been considered to be important regulators of gene expression in a range of biological processes in plants. A large number of lncRNAs have been identified in plants. However, most of their biological functions still remain to be determined. Here, we identified total 3 004 lncRNAs in cassava under normal or cold-treated conditions from Iso-seq data. We further characterized a lincRNA, CRIR1, as a novel positive regulator of the plant response to cold stress. CRIR1 can be significantly induced by cold treatment. Overexpression of CRIR1 in cassava enhanced the cold tolerance of transgenic plants. Transcriptome analysis demonstrated that CRIR1 regulates a range of cold stress-related genes in a CBF-independent pathway. We further found that CRIR1 RNA can interact with MeCSP5, a homolog of the cold shock protein that acts as RNA chaperones, indicating that CRIR1 may recruit MeCSP5 to improve the translation efficiency of mRNA. In summary, our study greatly extends the repertoire of lncRNAs in plants as well as its responding to cold stress. Moreover, it reveals a sophisticated mechanism by which CRIR1 regulates plant cold stress response by modulating the expression of stress-responsive genes and increasing the translational yield.
ArVirInd - a database of arboviral antigenic proteins from the Indian subcontinent
Nitin Atre
Kalichamy Alagarasu

Nitin Atre

and 2 more

October 15, 2021
Studies on antigenic proteins for arboviruses are important for providing diagnostics and vaccine development. India and its neighbouring countries have huge burden of arboviral diseases. Data mining for country-specific sequences from existing databases is cumbersome and time-consuming. This necessitated the development of a database of antigenic proteins from arbo-viruses isolated from the countries of the Indian subcontinent. Arboviral antigenic protein sequences were obtained from the NCBI and other databases. In silico antigenic characterization was performed (Epitope predictions) and data incorporated in the database. The front end is designed and developed using HTML, CSS and PHP. For the backend of the database, we have used MySQL. A database, named ArVirInd, is created as a repository of information on antigenic proteins. This enlists sequences by country and year of outbreak or origin of the viral strain. For each entry antigenic information is provided along with functional sites, etc. Researchers can search this database by virus/protein name, country and year of collection (or in combination). It is available publicly via Internet at http://www.arvirind.co.in. ArVirInd will be useful in the study of immuno-informatics, diagnostics and vaccinology for arboviruses.
‘Fluvial’ from ‘Dorset Waterbodies, a Common / Weal’, Helen Moore
Helen Moore

Helen Moore

October 15, 2021
‘Fluvial’, excerpt from ‘Dorset Waterbodies’, a new landscape ecopoem by Helen Moore
Brain thermal kinetics at brain-eyelid thermal tunnels overcoming COVID-19 thermometr...

M Marc Abreu

and 11 more

October 19, 2021
For centuries, temperature measurement deficiencies attributable to biological barriers and low thermo-conductivity (k) have precluded accurate surface-based fever assessment. At this stage of the pandemic, infection detection in children (who due to immature immune system may not effectively respond to vaccines) is critical because children can be readily infected and also become a large mutation reservoir. We reveal hitherto-unrecognized worldwide body temperature measurements (T°), in children and adults, over tissue typified by low-k similar to wood that may reach 6.8°C in thermal variability, hampering thereby COVID-19 control. Brain-eyelid thermal tunnels’ (BTT) integration of low-k and high-k regions creating a thermal pathway for undisturbed heat transmission from hypothalamus to high-k skin eliminates current shortcomings and makes the brain indispensable for defeating COVID-19 given that brain thermoregulatory signals are not limited by mutations. Anatomo-histologic, emissive, physiologic, and thermometric bench-to-bedside studies characterized and overcome biophysical limitations of thermometry through high-k eyelid-enabled brain temperature measurements in children and adults. BTT eyelid features fat-free skin (~900 µm) and unique light emission through a blood/fat configuration in the underlying tunnel. Contrarily, forehead features variable and thick dermis (2000–2500 µm) and variable fat layers (1100–2800 µm) resulting in variable low-k as well as temperatures 1.97 °C lower than BTT temperature (BTT°). Highest emission present in only ~3.1% of forehead averaged 1.08±0.49 °C (mean±SD) less than BTT° (p=0.008). Environmental and biological impacts during fanning revealed thermal imaging limitations for COVID-19 screening. Comparison of paired measurements for 100 pediatric patients showed that in the children subgroup above 37°C, BTT° exceeded body core temperature (Core°) in 60/72 patients; the average difference in the 72 patients was 0.62±0.7°C  (p<0.001 by unpaired t-test); and in the subgroup beyond 37.5°C, BTT° exceeded Core° in 30/32 patients. Delineating hypothalamic activity in children facilitates early infection detection, which is essential because children’s immunogenicity prevents effective vaccination and causes accelerated viral evolution. Capturing hypothalamic thermal signals from BTT was further supported by brain thermal kinetics via BTT using wearables during anesthesia, sedation, sleep, brain injury, exercise, and asymptomatic infection, which revealed brain/core discordance and enabled automated noninvasive afebrile infection detection for interrupting asymptomatic human-to-human transmission. BTT-based spot-check thermometry can be harmlessly implemented for children worldwide without undue burden and costs; meanwhile, continuous brain-eyelid T° in concert with biological and physical principles affords a new dimension for combating pandemics. The “detection–vaccination” pair solution presented is required to mitigate COVID-19 from spreading indefinitely through mutations and vaccine evasion while opening a viable path for eradicating COVID-19.
Systematic meta-analysis of subsequent pregnancy outcomes in recurrent pregnancy loss...
Peng-Sheng Zheng
Shan Li

Peng-Sheng Zheng

and 2 more

October 14, 2021
Background Parental abnormal chromosomal karyotypes are considered as reasons for recurrent pregnancy loss. Objective This systematic meta-analysis evaluated the current evidence on pregnancy outcomes amongst couples with abnormal versus normal chromosomal karyotypes. Search strategy Two independent reviewers screened titles and abstracts identified in EMBASE and PubMed from inception to January 2021. Selection criteria Studies were included if they provided a description of pregnancy outcomes of parental chromosomal abnormality. Data collection and analysis Random effects meta-analysis was used to compare odds of pregnancy outcomes associated with noncarriers and carriers. Main results A significantly lower first pregnancy live birth rate (FPLBR) was found in carriers than in noncarriers with RPL (OR: 0.55; 95% CI: 0.46-0.65; p<0.00001). Regarding FPLBR between translocation or inversion carriers and noncarriers, a markedly decreased FPLBR was found in translocation (OR: 0.44; 95% CI: 0.31–0.61; p<0.00001) but not inversion carriers. The accumulated live birth rate (ALBR) (OR: 0.96; 95% CI: 0.90–1.03; p=0.26) was similar, while the miscarriage rate (MR) of accumulated pregnancies (OR: 2.21; 95% CI: 1.69–2.89; p<0.00001) was significantly higher in the carriers than in noncarriers with RPL. The ALBR was not significant (OR: 1.82; 95% CI: 0.38–8.71; p=0.45) but the MR (OR: 5.75; 95% CI: 2.57–12.86; p<0.0001) was markedly lower for carriers who choose PGD than natural conception. Conclusions Carriers with RPL had higher risk of miscarriage but obtained a satisfying pregnancy outcome through multiple attempts. No sufficient evidence was found PGD could enhance the ALBR but it was an alternative to decrease the MR.
Occurrence of malformed calves in April - May 2021 indicates an unnoticed 2020 emerge...
Jorgen Agerholm
Kerstin Wernike

Jorgen Agerholm

and 1 more

October 14, 2021
During the European emergence of Schmallenberg virus (SBV) in 2011, examination of Culicoides spp. showed that SBV infected midges were present across Denmark. However, SBV associated malformations in ruminant species have not been reported in Denmark. In April 2021, seven calves with severe congenital generalized arthrogryposis and reduced body weight originating from a narrow region of the Jutlandic peninsula were submitted for examination. Analysis of fetal brain tissue for SBV viral RNA and pleural effusion for fetal anti-SBV antibodies identified SBV as the cause of the congenital syndrome. Backwards calculation from the calving dates indicated the occurrence of an unnoticed emergence of SBV in Denmark from early August 2020 and during the late summer and autumn. As SBV associated malformations may lead to dystocia urging for fetotomy or Cesarean section, veterinarians performing obstetric intervention are first line personnel in recognition of SBV emergence in domestic ruminants.
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