bluuebunny/crossref_metadata_2025_split huggingface dataset:
Koisio Technology-Modulated Cell Culture Media can Lead to Markedly Increased Intracellular ATP Levels of Fibroblast Cell Cultures
Authors: Men Yinghui , Zhang Mingchao , Zhu Qi , Ying Weihai 
Published: March 2022

AbstractIt has been reported that Koisio technology-modulated water without external additions of any substances can enter several types of aquaporins with significantly higher rate. In this study we determined the effects of Koisio technology-modulated cell culture media (Koisio media) on the energy state of cells. We found that for the lung fibroblast (L929) cell cultures, Koisio media without any additions of external substances led to approximately an 57% increase in the intracellular ATP levels of the cell cultures at the Cell Passage 6 - 18, compared with regular cell culture media. Seemingly surprisingly, we did not find that Koisio media could significantly affect the mitochondrial membrane potential of the cells, compared with regular cell culture media. Collectively, our study has provided first evidence indicating that Koisio media can lead to remarkable increases in the intracellular ATP levels of the L929 cell cultures, suggesting significant potential of Koisio technology in generating energy-enhancing water. Our finding that Koisio media did not affect the mitochondrial membrane potential has suggested that novel mechanisms may underlie the effects of Koisio media on cellular energy.
ABA-IMPORTING TRANSPORTER 1.1 activity in the endosperm of tomato seeds restrains germination under salinity stress
Authors: Shohat Hagai , Cheriker Hadar , Cohen Amir , Weiss David 
Published: March 2022

AbstractThe plant hormone abscisic acid (ABA) has a central role in the regulation of seed maturation and dormancy. ABA also restrains germination under abiotic-stress conditions. Here we show in tomato (Solanum lycopersicum) that the ABA importer ABA-IMPORTING TRANSPORTER 1.1 (AIT1.1) has a role in radicle emergence following imbibition. AIT1.1 expression was upregulated during imbibition, and CRISPR/Cas9-derived ait1.1 mutant seeds exhibited faster radicle emergence, increased germination and partial resistance to ABA. AIT1.1 was highly expressed in the endosperm, but not in the embryo, and ait1.1 isolated embryos did not show resistance to ABA. On the other hand, loss of AIT1.1 activity promoted the expression of endosperm-weakening related genes, and seed-coat scarification eliminated the promoting effect of ait1.1 on radicle emergence. Therefore, we propose that imbibition-induced AIT1.1 expression in the endosperm, mediates ABA-uptake into endosperm cells to restrain endosperm weakening. While salinity conditions strongly inhibited the wild-type (WT) M82 seed germination, it had much weaker effect on ait1.1 germination. We suggest that this AIT1.1 function was evolved to inhibit germination under unfavorable conditions, such as salinity. Unlike other ABA mutants, ait1.1 exhibited normal seed longevity, and therefore, the ait1.1 allele may have a potential for improving seed germination in crops.
Stage dependent differential influence of metabolic and structural networks on memory across Alzheimer’s disease continuum
Authors: Ng Kok Pin , Qian Xing , Ng Kwun Kei , Ji Fang , Rosa-Neto Pedro , Gauthier Serge , Kandiah Nagaendran , Zhou Juan Helen ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: March 2022

ABSTRACTBackgroundLarge-scale neuronal network breakdown underlies memory impairment in Alzheimer’s disease (AD). However, the differential trajectories of the relationships between network organization and memory across pathology and cognitive stages in AD remain elusive. We determined whether and how the influences of individual-level structural and metabolic covariance network integrity on memory varied with amyloid pathology across clinical stages without assuming a constant relationship.Methods708 participants from the Alzheimer’s Disease Neuroimaging Initiative were studied. Individual-level structural and metabolic covariance scores in higher-level cognitive and hippocampal networks were derived from magnetic resonance imaging and [18F]fluorodeoxyglucose positron emission tomography using seed-based partial least square analyses. The non-linear associations between network scores and memory across cognitive stages in each pathology group were examined using sparse varying coefficient modelling.ResultsWe showed that the associations of memory with structural and metabolic networks in the hippocampal and default mode regions exhibited pathology-dependent differential trajectories across cognitive stages using sparse varying coefficient modelling. In amyloid pathology group, there was an early influence of hippocampal structural network deterioration on memory impairment in the preclinical stage, and a biphasic influence of the angular gyrus-seeded default mode network metabolism on memory in both preclinical and dementia stages. In non-amyloid pathology groups, in contrast, the trajectory of the hippocampus-memory association was opposite and weaker overall, while no metabolism covariance networks were related to memory. Key findings were replicated in a larger cohort of 1280 participants.ConclusionsOur findings highlight potential windows of early intervention targeting network breakdown at the preclinical AD stage.
Mucin-degrading gut bacteria promote anti-parasitic immunity
Authors: Wolter Mathis , Boudaud Marie , Grant Erica T. , Parrish Amy , De Sciscio Alessandro , Thompson Seona , Gerardy Jean-Jacques , Mittelbronn Michel , Thornton David J. , Macpherson Andrew J. , Grencis Richard K. , Desai Mahesh S. 
Published: March 2022

AbstractBACKGROUND & AIMSHost-secreted gastrointestinal mucus plays a key role in the expulsion of intestinal nematode parasites. A balance between mucin secretion by the host and the gut microbial mucin foraging is essential to maintain the intestinal homeostasis, yet little is known about how changes in the mucin–microbiome interactions affect worm infections. Here, we aimed to examine how mucin foraging activity by the microbiome changes the course of parasitic worm infections by modulating the host immune responses.METHODSWe utilized a gnotobiotic mouse model containing a synthetic human gut microbiota that allows for: 1) a complete removal of the mucin-degrading bacteria from the community; and 2) diet-driven manipulation of the microbiota toward mucin foraging. We infected mice with a murine nematode,Trichuris muris, which resembles human infection withTrichuris trichiura. We examined the temporal dynamics of worm infection including worm burden and the host immune responses, and coupled these readouts to the microbial changes and mucin foraging activity.RESULTSThe absence of mucin-degrading bacteria in the microbiota enhances susceptibility to parasitic infection—evidenced by higher worm number—by promoting stronger Th1 immune responses. Dietary fiber deprivation increases the microbial mucin-foraging activity, which coincides with a shift in host immune responses from susceptible (chronic, Th1 type) to resistant (acute, Th2 type), thereby promoting worm clearance.CONCLUSIONSOur results provide mechanistic insights into how the colonic mucin-degrading bacteria promote anti-parasitic immunity through modulation of the host immune responses. Our study documents a clinically-relevant, novel link in the microbiome–parasite–host immune axis that is useful prerequisite knowledge in managing parasitic infections.
Drastic differential CRISPR-Cas9 induced mutagenesis influenced by DNA methylation and chromatin features
Authors: Weiss Trevor , Crisp Peter A. , Rai Krishan M. , Song Meredith , Springer Nathan M. , Zhang Feng 
Published: March 2022

AbstractCRISPR-Cas9 mediated genome editing has been widely adopted for basic and applied biological research in eukaryotic systems. While many studies considered DNA sequences of CRISPR target sites as the primary determinant for CRISPR mutagenesis efficiency and mutation profiles, increasing evidence revealed the significant role of chromatin context. Nonetheless, most of the prior studies were limited by the lack of sufficient epigenetic resources and/or by only transiently expressing CRISPR-Cas9 in a short time window. In this study, we leveraged the wealth of high-resolution epigenomic resources in Arabidopsis thaliana to address the impact of chromatin features on CRISPR-Cas9 mutagenesis using stable transgenic plants. Our results indicated that DNA methylation and chromatin features could lead to significant variations in mutagenesis efficiency by up to 250 folds. Low mutagenesis efficiencies were mostly associated with repressive heterochromatic features. This repressive effect appeared to persist through cell divisions but could be alleviated through substantial reduction of DNA methylation at CRISPR target sites. Moreover, specific chromatin features, such as H3K4me1, H3.3, and H3.1, appear to be associated with significant variations in CRISPR-Cas9 mutation profiles reflected by the 1 bp insertion rates. Our findings provided strong evidence that specific chromatin features could have significant and lasting impacts on both CRISPR-Cas9 mutagenesis efficiency and DNA double strand break repair outcomes.
Self-organizing Single-Rosette Brain Organoids from Human Pluripotent Stem Cells
Authors: Tidball Andrew M. , Niu Wei , Ma Qianyi , Takla Taylor N. , Walker J. Clayton , Margolis Joshua L. , Mojica-Perez Sandra P. , Sudyk Roksolana , Moore Shannon J. , Chopra Ravi , Shakkottai Vikram G. , Murphy Geoffrey G. , Li Jun Z. , Parent Jack M. 
Published: March 2022

ABSTRACTThe field of brain organoid research is complicated by morphological variability with multiple neural rosette structures per organoid. We have developed a new human brain organoid technique that generates self-organizing, single-rosette spheroids (SOSRS) with reproducible size, cortical-like lamination, and cell diversity. Rather than patterning a 3-dimensional embryoid body, we initiate brain organoid formation from a 2-dimensional monolayer of human pluripotent stem cells (hPSCs) that is patterned with small molecules into neuroepithelium and differentiated to cells of the developing dorsal cerebral cortex. This approach recapitulates the 2D to 3D transition from neural plate to neural tube that occurs during neurodevelopment. The vast majority of monolayer fragments form spheres with a single central lumen and consistent growth rates. Over time, the SOSRS develop appropriately ordered lamination consistent with six cortical layers by immunocytochemistry and single cell RNA-sequencing. The reproducibility of this method has allowed us to demonstrate robust structural phenotypes arising from chemical teratogen exposure or when modeling a genetic neurodevelopmental epileptic disorder. This platform should advance studies of human cortical development, brain disorder mechanisms, and precision therapies.SUMMARY STATEMENTSimple procedure for generating reproducible single rosette cortical brain organoids used to identify robust structural phenotypes with neuroteratogen exposure and in a genetic neurodevelopmental disease model.
Sex differences in contextual pattern separation, activation of new neurons, and functional connectivity within the limbic system
Authors: Yagi Shunya , Lee Amanda , Truter Nadine , Galea Liisa AM 
Published: March 2022

AbstractSex differences in the structure and function of hippocampus exist. Here, we examined sex differences in contextual pattern separation, functional connectivity, and activation of new neurons during fear memory. Two-month-old male and female Sprague-Dawley rats were injected with the DNA synthesis markers, iododeoxyuridine (IdU) and chlorodeoxyuridine (CldU) three weeks and four weeks before perfusion, respectively. One week after CldU injection, the rats underwent a context discrimination task in which rats were placed in context A (shock) and context A’ (no shock) every day for 12 days. On the test day, rats were placed in the shock context (context A) to measure fear memory and expression of zif268, an immediate early gene across 15 different limbic and reward regions. We found that females, but not males, showed contextual discrimination during the last days of training. On the test day, both sexes displayed similar levels of freezing, indicating equivalent fear memory for context A. Despite similar fear memory, males showed more positive correlations of zif268 activation between the limbic regions and the striatum, whereas females showed more negative correlations among these regions. Females showed greater activation of the frontal cortex, dorsal CA1, and 3-week-old adult-born dentate granular cells compared to males. These results highlight the importance of studying sex differences in fear memory and the contribution of adult neurogenesis to the neuronal network and may contribute to differences in susceptibility to fear related disorders such as posttraumatic stress disorder.
A quartz crystal microbalance method to quantify the size of hyaluronan and other glycosaminoglycans on surfaces
Authors: Srimasorn Sumitra , Souter Luke , Green Dixy E. , Djerbal Lynda , Goodenough Ashleigh , Duncan James A. , Roberts Abigail R. E. , Zhang Xiaoli , Débarre Delphine , DeAngelis Paul L. , Kwok Jessica C. F. , Richter Ralf P. 
Published: March 2022

AbstractHyaluronan (HA) is a major component of peri- and extra-cellular matrices and plays important roles in many biological processes such as cell adhesion, proliferation and migration. The abundance, size distribution and presentation of HA dictate its biological effects and are also useful indicators of pathologies and disease progression. Methods to assess the molecular mass of free-floating HA and other glycosaminoglycans (GAGs) are well established. In many biological and technological settings, however, GAGs are displayed on surfaces, and methods to obtain the size of surface-attached GAGs are lacking. Here, we present a method to size HA that is end-attached to surfaces. The method is based on the quartz crystal microbalance with dissipation monitoring (QCM-D) and exploits that the softness and thickness of films of grafted HA increase with HA size. These two quantities are sensitively reflected by the ratio of the dissipation shift (ΔD) and the negative frequency shift (-Δf) measured by QCM-D upon the formation of HA films. Using a series of size-defined HA preparations, ranging in size from ∼2 kDa tetrasaccharides to ∼1 MDa polysaccharides, we establish a monotonic yet non-linear standard curve of the ΔD/-Δf ratio as a function of HA size, which reflects the distinct conformations adopted by grafted HA chains depending on their size and surface coverage. We demonstrate that the standard curve can be used to determine the mean size of HA, as well as other GAGs, such as chondroitin sulfate and heparan sulfate, of preparations of previously unknown size in the range from 1 to 500 kDa, with a resolution of better than 10%. For polydisperse samples, our analysis shows that the process of surface-grafting preferentially selects smaller GAG chains, and thus reduces the average size of GAGs that are immobilised on surfaces comparative to the original solution sample. Our results establish a quantitative method to size HA and other GAGs grafted on surfaces, and also highlight the importance of sizing GAGs directly on surfaces. The method should be useful for the development and quality control of GAG-based surface coatings in a wide range of research areas, from molecular interaction analysis to biomaterials coatings.
Hedgehog signaling is non-cell autonomously activated in the cystic kidney of Arl13b mutant mice
Authors: Hsieh Chia-Ling , Jerman Stephanie Justine , Sun Zhaoxia 
Published: March 2022

ABSTRACTBackgroundPolycystic kidney disease (PKD) is a ciliopathy characterized by fluid-filled epithelial cysts in the kidney. Although it is well established that the primary cilium is essential for Hedgehog (HH) signalling and HH signalling is abnormally activated in cystic kidneys of multiple PKD models, the mechanism and function of HH activation in PKD pathogenesis remains incompletely understood.MethodsWe used a transgenic HH reporter line to identify the target tissue of HH signalling in Arl13f/f;Ksp-Cre mutant kidney, in which the cilia biogenesis gene Arl13b is specifically deleted in epithelial cells of the distal nephron. In addition, we treated Arl13bf/f;Ksp-Cre mice with the GLI inhibitor GANT61 and analyzed its impact on PKD progression in this model.ResultsIn vivo in the mouse kidney, deletion of Arl13b in epithelial cells led to non-cell autonomous activation of the HH pathway in the interstitium. In addition, whole body inhibition of the HH pathway by GANT61 reduced cyst burden, suppressed fibrosis and reduced kidney function decline in Arl13bf/f;Ksp-Cre mice.ConclusionsOur results reveal non-cell autonomous activation of HH signalling in the interstitium of the cystic kidney of Arl13bf/f;Ksp-Cre mice and suggest that abnormal activation of the HH pathway contributes to PKD progression.
Insights into the role of Nup62 and Nup93 in assembling cytoplasmic ring and central transport channel of the nuclear pore complex
Authors: Madheshiya Pankaj K. , Shukla Ekta , Singh Jyotsna , Bawaria Shrankhla , Ansari Mohammed Yousuf , Chauhan Radha 
Published: March 2022

ABSTRACTThe nuclear pore complex (NPC) is a highly modular assembly of 34 distinct nucleoporins (Nups), to form a versatile transport channel between the nucleus and cytoplasm. Among them, Nup62 is known as an essential component for nuclear transport while, Nup93 for the proper nuclear envelope assembly. These Nups constitute various NPC subcomplexes: such as central transport channel (CTC), cytoplasmic ring (CR) and inner ring (IR). However, how they play their role in the NPC assembly and transport activity is not clear. Here we delineated the interacting regions, conducted biochemical reconstitution and structural characterization of the mammalian CR complex to reveal its intrinsic dynamic behaviour and a distinct ‘4’ shaped architecture resembling the CTC complex. Our data demonstrate that Nup62 coiled-coil domain is critical to form both Nup62•Nup88 and Nup62•Nup88•Nup214 heterotrimers and both can bind to the Nup93. We therefore propose that Nup93 act as a ‘sensor’ to bind to Nup62 shared heterotrimers including Nup62•Nup54 heterotrimer of the CTC, which was not shown previously as an interacting partner. Altogether, our study establishes that the Nup62 via its coiled-coil domain is central to form compositionally distinct yet structurally similar heterotrimers, and the Nup93 anchors these diverse heterotrimers by recognizing them non-selectively.
CircRNA_33702 promotes renal fibrosis by targeting the miR-29b-3p/WISP1 pathway
Authors: Ai Kai , Yi Lei , Wang Yinhuai 
Published: March 2022

AbstractGrowing evidence suggest that circular RNAs (circRNAs) are critical mediators in renal diseases. However, there have been very few reports about the role of circRNAs in renal fibrosis. In this study, circRNA_33702 was found to be upregulated, both in UUO mice and in TGF-β 1-treated BUMPT cells. Whilst knockdown of circRNA_33702 was shown to relieve the TGF-β 1-induced expression of collagen I, collagen III and fibronectin; overexpression of circRNA_33702 was found to exert an inhibitory effect on the expression of the same genes. Mechanistically, circRNA_33702 was demonstrated to bind directly with miR-29b-3p and inhibit its expression. Moreover, WISP1 was identified as a target of miR-29b-3p and the expression of WISP1 was observed to be repressed by miR-29b-3p. Notably, knockdown of circRNA_33702 was found to attenuate the expression of collagen I, collagen III and fibronectin by inhibiting the expression of WISP1, and the observed inhibitory effect can be reversed by miR-29b-3p inhibitor. Finally, inhibition of circRNA_33702 was shown to attenuate interstitial fibrosis in UUO mice via the miR-29b-3p/WISP1 axis. In general, our data show that circRNA_33702 may promote renal fibrosis via the miR-29b-3p/WISP1 axis, which may potentially be developed as a new therapeutic target.
Variability in SARS-Cov-2 IgG Antibody Affinity To Omicron and Delta Variants in Convalescent and Community mRNA Vaccinated Individuals
Authors: Tu Michael K. , Chiang Samantha H. , Wong David T.W. , Strom Charles M 
Published: March 2022

AbstractThe emergence of Omicron and Delta variants of SARS-CoV-2 has begun a number of discussions regarding breakthrough infection, waning immunity, need and timing for vaccine boosters and whether existing mRNA vaccines for the wildtype strain are adequate. Our work leverages a biosensor-based technique to evaluate the binding efficacy of SARS-CoV-2 S1 specific salivary antibodies to the Omicron and Delta variants using a cohort of mRNA vaccinated (n=109) and convalescent (n=19) subjects. We discovered a wide range of binding efficacies to the variant strains, with a mean reduction of 60.5%, 26.7%, and 14.7% in measurable signal to the Omicron strain and 13.4%, 2.4%, and −6.4% percent mean reduction to the Delta Variant for convalescent, Pfizer, and Moderna vaccinated groups respectively. This assay may be an important tool in determining susceptibility to infection or need for booster immunization as the pandemic evolves.Key PointsAMPERIAL assay developed to quantify salivary SARS-CoV-2 S1 IgG antibodies to Omicron and Delta variantsThere was a reduction in affinity to both Delta and Omicron VariantsThe reduction in affinity was more pronounced to Omicron than for Delta VariantsThere was a significant difference between IgG affinities in Individuals vaccinated with Pfizer versus Moderna Vaccines
Association of the medical therapy with beta-blockers or inhibitors of renin-angiotensin system with clinical outcomes in patients with mildly reduced left ventricular ejection fraction after acute myocardial infarction
Authors: Joo Seung-Jae , Kim Song-Yi , Lee Jae-Geun , Choi Joon-Hyouk , Park Hyeung Keun , Beom Jong Wook , Boo Ki Yung , Yoon Chang-Hwan , Lee Jung-Hee , Hur Seung-Ho , Chae Jei Keon , Jeong Myung Ho 
Published: March 2022

AbstractIn the era of the initial optimal interventional and medical therapy for acute myocardial infarction (AMI), a number of patients with mildly reduced left ventricular ejection fraction (EF) (41 - 49%) have been increasing. This observational study aimed to investigate the association between the medical therapy with oral beta-blockers or inhibitors of renin-angiotensin system (RAS) and 2-year clinical outcomes in patients with mildly reduced EF after AMI. Among patients enrolled in the Korea Acute Myocardial Infarction Registry-National Institute of Health, propensity-score matched patients who survived the initial attack and had mildly reduced EF were selected according to beta-blocker or RAS inhibitor therapy at discharge. Beta-blocker therapy at discharge was associated with lower 2-year major adverse cardiac events which was a composite of cardiac death, myocardial infarction, revascularization and re-hospitalization due to heart failure (8.7 vs. 12.8/100 patient-years; hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.50-0.93; P=0.015), and no significant interaction between EF ≤45% and >45% was observed (Pinteraction=0.354). This association was mainly driven by lower myocardial infarction in patients with beta-blockers (HR 0.50; 95% CI 0.26-0.95; P=0.035). Inhibitors of RAS at discharge were associated with lower re-hospitalization due to heart failure (1.8 vs. 3.5/100 patient-years; HR 0.53; 95% CI 0.33-0.86; P=0.010) without a significant interaction between EF ≤45% and >45% (Pinteraction=0.333). In patients with mildly reduced EF after AMI, the medical therapy with beta-blockers or RAS inhibitors at discharge was associated with better 2-year clinical outcomes.