bluuebunny/crossref_metadata_2025_split huggingface dataset:
Superior prognostic value of three-dimensional echocardiography-derived right ventricular ejection fraction: a meta-analysis
Authors: Sayour Alex Ali , Tokodi Márton , Celeng Csilla , Takx Richard A. P. , Fábián Alexandra , Lakatos Bálint K. , Friebel Rocco , Surkova Elena , Merkely Béla , Kovács Attila 
Published: June 2022

ABSTRACTAimsWe aimed to confirm that three-dimensional echocardiography (3DE)-derived right ventricular (RV) ejection fraction (EF) is a more robust predictor of adverse cardiopulmonary outcomes than the conventional echocardiographic parameters.Methods and ResultsWe performed a meta-analysis of studies reporting the impact of unit change of RVEF, tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and free-wall longitudinal strain (FWLS) on clinical outcomes (all-cause mortality and/or adverse cardiopulmonary outcomes). Hazard ratios (HR) were rescaled by the within-study standard deviations (SD) to represent standardized changes. Within each study, we calculated the ratio of HRs related to 1 SD reduction in RVEF versus TAPSE, or FAC, or FWLS, to quantify the predictive value of RVEF relative to the other metrics. These ratios of HRs were pooled using random-effects models.Ten independent studies were identified as suitable, including data on 1,928 patients with various cardiopulmonary conditions. Overall, 1 SD reduction in RVEF was robustly associated with adverse outcomes (HR: 2.64 [95% CI: 2.18 to 3.20], p<0.001; heterogeneity: I2=65%, p=0.002). In studies reporting HRs for RVEF and TAPSE, FAC, or FWLS in the same cohort, RVEF had superior predictive value per SD reduction versus the other three parameters (vs. TAPSE, HR: 1.54 [95% CI: 1.04 to 2.28], p=0.031; vs. FAC, HR: 1.45 [95% CI: 1.15 to 1.81], p=0.001; vs. FWLS, HR: 1.44 [95% CI: 1.07 to 1.95], p=0.018).Conclusion3DE-derived RVEF has superior prognostic value compared with conventional RV indices, therefore, it might further refine the risk stratification of patients with cardiopulmonary diseases.Graphical AbstractAdded predictive value of three-dimensional (3D) echocardiography-derived right ventricular ejection fraction (RVEF) versus conventional metrics of RV systolic function on clinical outcomes: a meta-analysis of 10 studies. FAC: fractional area change, FWLS: free-wall longitudinal strain, HR: hazard ratio, SD: standard deviation, TAPSE: tricuspid annular plane systolic excursion
Osmotic stress response in BetP: How lipids and K+ team up to overcome downregulation
Authors: Heinz Veronika , Güler Günnur , Leone Vanessa , Madej M. Gregor , Maksimov Stanislav , Gärtner Rebecca M. , Rudi Olga , Hamdi Farzad , Kastritis Panagiotis L. , Mäntele Werner , Krämer Reinhard , Forrest Lucy R. , Perez Camilo , Ziegler Christine 
Published: June 2022

AbstractThe trimeric betaine symporter BetP senses an osmotic upshift via its osmosensory C-terminal domain and responds rapidly with a steep increase in transport rate. Full activation requires both an elevated internal K+ concentration and a yet unknown membrane stimulus. Moreover, the molecular mechanisms of stress sensing and upregulation remain unclear. Here, we show that K+ binding to BetP in vivo is highly cooperative. Using X-ray crystallography, we identify four putative K+ interaction sites at the C-terminal domains of BetP. Single particle CryoEM on BetP reconstituted in amphipols (AMP-BetP), in the absence of K+, revealed that the three C-terminal domains are oriented symmetrically near the membrane surface, representing a new downregulated state. The presence of K+ resulted in asymmetric partial unfolding of the C-terminal domains, which was assigned as an intermediate between the downregulated state and the conformation observed in crystal structures. Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy in 2D crystals of BetP reveal glutamate/aspartate and tyrosine responses to K+, in agreement with the identified K+ interaction sites, as well as specific unfolding events in the C-terminal domain upon activation. A rearrangement of the relative protomer orientations confers upregulation through key structural elements involved in the alternating access of BetP affecting sodium and betaine binding affinities. Although K+-specific regulation is unique to BetP we discuss unfolding/refolding of sensory domains as a unifying element in hyperosmotic stress response of osmoregulated transporters.
Inhibition of Tgfβ signaling enables durable ventricular pacing by TBX18 gene transfer
Authors: Fan Jinqi , Kim Nam Kyun , Fernandez Natasha , Kim Tae Yun , Li Jun , Wolfson David , Cho Hee Cheol 
Published: June 2022

ABSTRACTImplantable cardiac pacemaker devices are generally effective for patients with symptomatic bradyarrhythmia. However, device-dependent cardiac pacing is far from ideal and often inadequate, particularly for pediatric patients who need to go through invasive revision of the indwelling hardware. Biological pacemakers have been proposed as device-free alternatives to the current treatment, but sustained, unwavering biological pacing beyond days after the biologic delivery has not been demonstrated. We have previously demonstrated that re-expression of an embryonic transcription factor, TBX18, could reprogram ventricular cardiomyocytes into induced pacemaker myocytes (iPMs). Here, we report that exogenous expression of TBX18 per se leads to severe fibrosis in situ, impairing the iPMs’ ability to pace together. Acute fibrosis is accompanied with proliferation and activation of cardiac fibroblasts via Tgfβ-Smad2/3 pathway. Small molecule inhibition of Tgfβ signaling mitigated the interstitial remodeling, independent from TBX18-induced iPM reprogramming at the single-cell level. Direct and focal gene transfer of TBX18 into the left ventricular myocardium created ventricular pacing in a rat model of chronic atrioventricular block, but such activity began to wane in a week. In contrast, a combination therapy consisting of TBX18 gene transfer and Tgfβ inhibition enabled sustained biological pacing beyond the four-week study period. Our data demonstrate that inhibition of Tgfβ signaling suffices to achieve durable cardiac pacing by TBX18-induced biological pacemakers.
Spatial metabolomics reveal divergent cardenolide processing in the monarch butterfly (Danaus plexippus) and the common crow (Euploea core)
Authors: Dreisbach Domenic , Bhandari Dhaka R. , Betz Anja , Tenbusch Linda , Vilcinskas Andreas , Spengler Bernhard , Petschenka Georg 
Published: June 2022

AbstractAlthough being famous for sequestering milkweed cardenolides, the mechanism of sequestration and where cardenolides are localized in caterpillars of the monarch butterfly (Danaus plexippus) is still unknown. While monarchs tolerate cardenolides by a resistant Na+/K+-ATPase, it is unclear how closely related species such as the non-sequestering common crow (Euploea core) cope with these toxins. Using novel atmospheric-pressure scanning microprobe matrix-assisted laser/desorption ionization mass spectrometry imaging, we compared the distribution of cardenolides in caterpillars ofD. plexippusandE. core. Specifically, we tested at which physiological scale quantitative differences between both species are mediated and how cardenolides distribute across body tissues. WhereasD. plexippussequestered most cardenolides from milkweed (Asclepias curassavica), no cardenolides were found in the tissues ofE. core. Remarkably, quantitative differences already manifest in the gut lumen: while monarchs retain and accumulate cardenolides above plant concentrations, the toxins are degraded in the gut lumen of crows. We visualized cardenolide transport over the monarch midgut epithelium and identified integument cells as the final site of storage where defenses might be perceived by predators. Our study provides molecular insight into cardenolide sequestration and highlights the great potential of mass spectrometry imaging for understanding the kinetics of multiple compounds including endogenous metabolites, plant toxins, or insecticides in insects.
Uncovering the evolutionary tail of GZMM: An NSP4 related protease
Authors: Hafeez Ahmer Bin , Ahmad Jamshaid 
Published: June 2022

AbstractSerine proteases are the most predominant class performing a number of activities in organisms. Undergoing several mutations in their sequence over a span of a billion years yet S1 chymotrypsin/trypsin family has maintained a common fold. Granule Associated Serine Peptidases of Immune Defense (GASPIDS) belonging to the S1 class, found in the granules of immune cells are explicitly involved in the regulation of immune-related functions possessing a conserved catalytic triad Ser-Asp-His. The neutrophils along with other cells express four serine proteases (ELA2, PR3, CTSG and NSP4) sharing certain common characteristics. Similarly, CTLs and NK cells express a set of proteases, Granzymes. This study infers an evolutionary relationship among GASPIDs. We employed computational strategies and found that a higher degree of similarity existed between NSP4 and GZMM as compared to their members i.e. NSPs and granzymes, respectively. Similarly, GZMM a protease of NK cells and t cells lineage is found in the Met-ase locus consisting of NSPs genes i.e.,Ela2, Prtn3andCtsg. The evolutionary relationship ofPrss57/NSP4 andgzmm/GZMM was reconstructed through empirical phylogenetic analysis which revealedPrss57/NSP4 to be closely related togzmm/GZMM. Additional co-expression analysis was carried out to determine the regulatory role ofPrss57, inducingGzmm. From this work, we inferred thatPrss57/NSP4 is closely related toGzmm/GZMM.
A modular T7-based gene expression platform in Pseudomonas putida: Construction and in silico analysis
Authors: Beentjes Marleen , Löwe Hannes , Pflüger-Grau Katharina , Kremling Andreas 
Published: June 2022

AbstractThe T7 RNA polymerase is considered one of the most popular tools for heterologous gene expression in the gold standard biotechnological host Escherichia coli. However, the exploitation of this tool in other prospective biotechnological hosts is still very scarce. To this intent, we established and characterized a modular T7 RNA polymerase-based system for heterologous protein production in Pseudomonas putida, using the model protein eGFP as an easy-to-quantify reporter protein. We have effectively targeted the limitations associated with the initial genetic set-up of the system, such as slow growth and low protein production rates. By replacing the T7-phage inherent TΦ terminator downstream of the heterologous gene with the synthetic tZ terminator, growth and protein production rates improved drastically, and the T7 RNA polymerase system reached a productivity level comparable to that of an intrinsic RNA polymerase based system. Furthermore, we could show that the system is saturated with T7 RNA polymerase by applying a T7 RNA polymerase ribosome binding site library to tune heterologous protein production. The saturation points to an essential role for the ribosome binding sites of the T7 RNA polymerase since, in an oversaturated system, cellular resources are lost to the synthesis of unnecessary T7 RNA polymerase. Eventually, we combined the experimental data into a model that can predict the eGFP production rate with respect to the relative strength of the ribosome binding sites upstream of the T7 gene.Abstract Figure
AlphaFold2 reveals commonalities and novelties in protein structure space for 21 model organisms
Authors: Bordin Nicola , Sillitoe Ian , Nallapareddy Vamsi , Rauer Clemens , Lam Su Datt , Waman Vaishali P. , Sen Neeladri , Heinzinger Michael , Littmann Maria , Kim Stephanie , Velankar Sameer , Steinegger Martin , Rost Burkhard , Orengo Christine 
Published: June 2022

AbstractOver the last year, there have been substantial improvements in protein structure prediction, particularly in methods like DeepMind’s AlphaFold2 (AF2) that exploit deep learning strategies. Here we report a new CATH-Assign protocol which is used to analyse the first tranche of AF2 models predicted for 21 model organisms and discuss insights these models bring on the nature of protein structure space. We analyse good quality models and those with no unusual structural characteristics, i.e., features rarely seen in experimental structures. For the ∼370,000 models that meet these criteria, we observe that 92% can be assigned to evolutionary superfamilies in CATH. The remaining domains cluster into 2,367 putative novel superfamilies. Detailed manual analysis on a subset of 618 of those which had at least one human relative revealed some extremely remote homologies and some further unusual features, but 26 could be confirmed as novel superfamilies and one of these has an alpha-beta propeller architectural arrangement never seen before. By clustering both experimental and predicted AF2 domain structures into distinct ‘global fold’ groups, we observe that the new AF2 models in CATH increase information on structural diversity by 36%. This expansion in structural diversity will help to reveal associated functional diversity not previously detected. Our novel CATH-Assign protocol scales well and will be able to harness the huge expansion (at least 100 million models) in structural data promised by DeepMind to provide more comprehensive coverage of even the most diverse superfamilies to help rationalise evolutionary changes in their functions.
massDatabase: utilities for the operation of the public compound and pathway database
Authors: Shen Xiaotao , Wang Chuchu , Snyder Michael P. 
Published: June 2022

AbstractSummaryOne of the major challenges in LC-MS data (metabolome, lipidome, and exposome) is converting many metabolic feature entries to biological function information, such as metabolite annotation and pathway enrichment, which are based on the compound and pathway databases. Multiple online databases have been developed, containing lots of information about compounds and pathways. However, there is still no tool developed for operating all these databases for biological analysis. Therefore, we developed massDatabase, an R package that operates the online public databases and combines with other tools for streamlined compound annotation and pathway enrichment analysis. massDatabase is a flexible, simple, and powerful tool that can be installed on all platforms, allowing the users to leverage all the online public databases for biological function mining. A detailed tutorial and a case study are provided in the Supplementary Materials.Availability and implementationhttps://massdatabase.tidymass.org/.Contactshenxt@stanford.edu and mpsnyder@stanford.eduSupplementary informationSupplementary data are available at Bioinformatics online.
Wheat pollen uptake of CRISPR/Cas9 RNP-PDMAEMA nanoassemblies results in targeted loss of gene function in progeny
Authors: Gogoi Neelam , Kanwal Mehwish , Norman Michael , Downs Jacob , Ahmad Nabil , Mago Rohit , Bariana Harbans , Müllner Markus , Bansal Urmil , Jones Brian 
Published: June 2022

AbstractThe utility of CRISPR in plants has remained limited by the dual difficulties of delivering the molecular machinery to target cells and the use of somatic cell techniques that require tissue culture-basedde novoorganogenesis. We developed 5-10 nm isodiametric polyplex nanoassemblies, comprising poly [2-(dimethylamino)ethylmethacrylate] PDMAEMA (PD) polycationic linear homopolymers and CRISPR/Cas9 ribonucleoproteins (RNPs), that enable endocytosis-driven RNP uptake into pollen grains. Pollen from wheat plants (genotype Gladius+Sr50), homozygous for monogenicSr50-mediated resistance to stem rust (Puccinia graminisf. sp. tritici -Pgt), were incubated with RNP/PD nanoassemblies targeting the dominant,Sr50rust resistance gene. The treated pollen grains were then used to fertilize Gladius+Sr50 florets and the resulting M1 plants were tested for loss ofSr50function via rust resistance screens. The identification of fully susceptible M1 seedlings indicated that theSr50RNPs acted on both alleles, indicating they were transferred via the treated pollen to the zygote. The ability to readily deliver CRISPR RNPs to reproductive cells via biodegradable, polymeric nanocomplexes has significant implications for the efficiency of gene editing in plants.
Confounding effects of heart rate, breathing rate, and frontal fNIRS on interoception
Authors: Candia-Rivera Diego , Sappia M. Sofía , Horschig Jörn M. , Colier Willy N. J. M. , Valenza Gaetano 
Published: June 2022

AbstractRecent studies have established that cardiac and respiratory phases can modulate perception and related neural dynamics. While heart rate and respiratory sinus arrhythmia possibly affect interoception biomarkers, such as heartbeat-evoked potentials, the relative changes in heart rate and cardiorespiratory dynamics in interoceptive processes have not yet been investigated. In this study, we investigated the variation in heart and breathing rates, as well as higher functional dynamics including cardiorespiratory correlation and frontal hemodynamics measured with fNIRS, during a heartbeat counting task. To further investigate the functional physiology linked to changes in vagal activity caused by specific breathing rates, we performed the heartbeat counting task together with a controlled breathing rate task. The results demonstrate that focusing on heartbeats decreases breathing and heart rates in comparison, which may be part of the physiological mechanisms related to “listening” to the heart, the focus of attention, and self-awareness. Focusing on heartbeats was also observed to increase frontal connectivity, supporting the role of frontal structures in the neural monitoring of visceral inputs. However, cardiorespiratory correlation is affected by both heartbeats counting and controlled breathing tasks. Based on these results, we concluded that variations in heart and breathing rates are confounding factors in the assessment of interoceptive abilities and relative fluctuations in breathing and heart rates should be considered to be a mode of covariate measurement of interoceptive processes.
Long non-coding RNA L13Rik promotes high glucose-induced mesangial cell injury by regulating miR-2861/CDKN1B axis
Authors: Sun Linlin , Ding Miao , Chen Fuhua , Zhu Dingyu , Xie Xinmiao 
Published: June 2022

AbstractDiabetic nephropathy (DN) is a frequent and severe microvascular complication of diabetes. Glomerular mesangial cell (MC) injury occurs at the initial phase of DN and acts as a critical role in the pathogenesis of DN. Given the importance of long non-coding RNA (lncRNA) in regulating MC hyperplasia and extracellular matrix (ECM) accumulation, it is essential to identify functional lncRNAs during MC injury. Here a novel lncRNA, C920021L13Rik (L13Rik for short), was identified to up-regulated in DN progression. The expression of L13Rik in DN patients and diabetic rats was assessed using quantitative real-time PCR (qRT-PCR), and the function of L13Rik on regulating HG-induced MC injury was assessed using cell counting kit-8 (CCK-8) and western blot assay to analyze MC viability and ECM accumulation. We found that L13Rik level was significantly increased while miR-2861 level was significantly decreased in peripheral blood of DN patients, renal tissues of diabetic rats, and HG-treated MCs. Functionally, both L13Rik depletion and miR-2861 overexpression effectively reduced HG-induced MC survival, ECM accumulation, and cell hypertrophy. Mechanistically, L13Rik functioned as a competing endogenous RNA (ceRNA) to sponge miR-2861, resulting in the de-repression of its target cyclin-dependent kinase inhibitor 1B (CDKN1B), a gene known to accelerate MC injury. Collectively, the current results demonstrate that up-regulated L13Rik is correlated with DN, and may be a hopeful therapeutic target for DN.
Association of Striatal Connectivity Gradients to Functional Domains Across Psychiatric Disorders
Authors: Mulders Peter C.R. , van Eijndhoven Philip F.P. , van Oort Jasper , Oldehinkel Marianne , Duyser Fleur A. , Kist Josina D. , Collard Rose M. , Vrijsen Janna N. , Haak Koen V. , Beckmann Christian F. , Tendolkar Indira , Marquand Andre F. 
Published: June 2022

AbstractObjectiveTo uncover transdiagnostic domains of functioning across stress- and neurodevelopmental disorders, and to map these on to the topographic functional organization of cortico-striatal circuitry.MethodsIn a clinical sample (n=186) of subjects with high rates of comorbidity of major depressive disorder, anxiety disorder, attention-deficit/hyperactivity disorder and/or autism spectrum disorder, we use exploratory factor analysis on a wide range of clinical questionnaires to identify consistent functional domains of symptomatology across disorders, then replicate these functional domains in an independent dataset (n=188). Then, we use canonical correlation analysis link these functional domains to the topographic organization of the striatum as represented by connectopic maps.ResultsWe reveal four functional domains that transcend current diagnostic categories relating to negative valence, cognition, social functioning and inhibition/arousal. These functional domains are replicated in an independent sample and are associated with the fine-grained topographical organization of functional connectivity in the striatum (out of sample r=0.20, p=0.026), a central hub in motor, cognitive, affective and reward-related brain circuits.Conclusions and relevanceFunctional domains across stress- and neurodevelopmental disorders are associated with the functional organization of the striatum. We propose that investigating psychiatric symptoms across disorders is a promising path to linking them to underlying biology, and can help bridge the gap between neuroscience and clinical psychiatry.
Population Transcriptome and Phenotype Reveal that theRht-D1bContribute a Larger Seedling Roots to Modern Wheat Cultivars
Authors: Wang Xiaoming , Zhao Peng , Guo Xiaolong , Liu Zihui , Ma Xiuyun , Zhao Yuqian , Lai Xiangjun , Huang Liuying , Wang Wanying , Han Dejun , Kang Zhensheng , Xu Shengbao 
Published: June 2022

ABSTRACTThe crop root system is pivotal for water and nutrient uptake. Although the breeding selection significantly increased the yield of modern wheat cultivars, then how this selection reshapes the root system remains largely unknown. Here we performed a large-scale transcriptomic and phenotypical investigations on the seedling root of 406 wheat accessions, which demonstrated modern cultivars (MC) had significantly changed in the root transcriptome and root development. The MC had a significantly larger seedling root system than that in landraces (LA), and this was mainly due to theRht-D1ballele introduction. Physiological and cytological investigations showed that theRht-D1bsuppressed gibberellin (GA) signaling, thus inhibiting the cell length in above-ground tissue but increasing the cell length in roots. This distinct regulation of GA signaling between above- and under-ground tissues contributed to MC having a significantly larger root-shoot ratio. Moreover,Rht-D1balso has a GA-independent role to enlarge root cell width that enhanced the root diameter, ultimately contribute to a larger root surface and volume to MC seedlings. These findings provide new insights to understand the successful application of GA-suppressing alleles in modern wheat breeding and its futural application to form a robust wheat root system.Short SummaryRht-D1bis the major allele that contribute a larger root system and higher root-shoot ratio to modern wheat cultivars.