bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of the Temporal Pole in Temporal Lobe Epilepsy: A Diffusion Kurtosis Imaging Study
Authors: Kasa Loxlan W , Peters Terry , Mirsattari Seyed M. , Jurkiewicz Michael T. , Khan Ali R. , Haast Roy A.M 
Published: October 2021

ABSTRACTObjectiveThis study aims to evaluate the use of diffusion kurtosis imaging (DKI) to detect microstructural abnormalities within the temporal pole (TP) in temporal lobe epilepsy (TLE) patients.MethodsDKI quantitative maps were obtained from fourteen lesional (MRI+) and ten non-lesional (MRI-) TLE patients, along with twenty-one healthy controls. This included mean (MK); radial (RK) and axial kurtosis (AK); mean diffusivity (MD) and axonal water fraction (AWF). Automated fiber quantification (AFQ) was used to quantify DKI measurements along the inferior longitudinal (ILF) and uncinate fasciculus (Unc). ILF and Unc tract profiles were compared between groups and tested for correlation with seizure duration. To characterize temporopolar cortex (TC) microstructure, DKI maps were sampled at varying depths from superficial white matter (WM) towards the pial surface. Each patient group was separated according to side ipsilateral to the epileptogenic temporal lobe and their AFQ results were used as input for statistical analyses.ResultsSignificant differences were observed between MRI+ and controls (p < 0.005), towards the most anterior of ILF and Unc proximal to the TP of the left (not right) ipsilateral temporal lobe for MK, RK, AWK and MD. Noticeable differences were also observed mostly towards the TP for MK, RK and AWK in the MRI-group. DKI measurements correlated with seizure duration, mostly towards the anterior segments of the WM bundles. Stronger differences in MK, RK and AWF within the TC were observed in the MRI+ and noticeable differences (except for MD) in MRI-groups compared to controls.SignificanceThe study demonstrates that DKI has potential to detect subtle microstructural alterations within the anterior segments of the ILF and Unc and the connected TC in TLE patients including MRI-subjects. This could aid our understanding of the extrahippocampal areas involved in seizure generation in TLE and might inform surgical planning, leading to better seizure outcomes.
High Expression of Glycolytic Genes in Clinical Glioblastoma Patients Correlates with Lower Survival
Authors: Stanke Kimberly M , Wilson Carrick , Kidambi Srivatsan 
Published: October 2021

AbstractGlioblastoma (GBM), the most aggressive brain tumor, is associated with a median survival at diagnosis of 16-20 months and limited treatment options. The key hallmark of GBM is altered tumor metabolism and marked increase in the rate of glycolysis. Aerobic glycolysis along with elevated glucose consumption and lactate production supports rapid cell proliferation and GBM growth. In this study, we examined the gene expression profile of metabolic targets in GBM samples from patients with low grade glioma (LGG) and GBM. We found that gene expression of glycolytic enzymes is up-regulated in GBM samples and significantly associated with an elevated risk for developing GBM. Our findings of clinical outcomes showed that GBM patients with high expression of HK2 and PKM2 in the glycolysis related genes and low expression of genes involved in mitochondrial metabolism-SDHB and COX5A related to tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS), respectively, was associated with poor patient overall survival. Surprisingly, expression levels of genes involved in mitochondrial oxidative metabolism are markedly increased in GBM compared to LGG but was lower compared to normal brain. The fact that in GBM the expression levels of TCA cycle and OXPHOS-related genes are higher than those in LGG patients suggests the metabolic shift in GBM cells when progressing from LGG to GBM. These results are an important step forward in our understanding of the role of metabolic reprogramming in glioma as drivers of the tumor and could be potential prognostic targets in GBM therapies.
WUSCHEL-Related Homeobox Genes Cooperate with Cytokinin Signalling to Promote Bulbil Formation in Lilium lancifolium
Authors: He Guoren , Cao Yuwei , Wang Jing , Song Meng , Bi Mengmeng , Tang Yuchao , Xu Leifeng , Yang Panpan , Ming Jun 
Published: October 2021

SummaryThe bulbil is an important vegetative reproductive organ in triploid Lilium lancifolium. Based on our previously obtained transcriptome data, we screened two WUSCHCEL-related homeobox (WOX) genes closely related to bulbil formation, LlWOX9 and LlWOX11. However, the biological functions and regulatory mechanisms of LlWOX9 and LlWOX11 are unclear. In this study, we cloned the full-length coding sequences of LlWOX9 and LlWOX11. Transgenic Arabidopsis showed increased branch numbers, and the overexpression of LlWOX9 and LlWOX11 in stem segments promoted bulbil formation, while the silencing of LlWOX9 and LlWOX11 inhibited bulbil formation, indicating that LlWOX9 and LlWOX11 are positive regulators of bulbil formation. Cytokinins acting through type-B response regulators (type-B RRs) could bind to the promoters of LlWOX9 and LlWOX11 and promote their transcription. LlWOX11 could enhance cytokinin pathway signalling by inhibiting the transcription of type-A LlRR9. Our study enriches the understanding of the regulation of plant development by the WOX gene family and lays a foundation for further research on the molecular mechanism of bulbil formation in lily.
Suppression of B-Cell Activation by Human Cord Blood-Derived Stem Cells (CB-SC) through the Galectin-9-Dependent Cell Contact Mechanism
Authors: Hu Wei , Song Xiang , Yu Haibo , Fan Sophia , Shi Andrew , Sun Jingyu , Wang Hongjun , Zhao Laura , Zhao Yong 
Published: October 2021

AbstractBackgroundWe developed the Stem Cell Educator therapy among multiple clinical trials based on the immune modulations of multipotent cord blood-derived stem cells (CB-SC) on different compartments of immune cells such as T cells and monocytes/macrophages in diabetes and other autoimmune diseases. However, the effects of CB-SC on the B cells remained unclear. To better understand the molecular mechanisms underlying the immune education of CB-SC, we explored the modulations of CB-SC on human B cells.MethodsCB-SC were isolated from human cord blood units and confirmed by flow cytometry with different markers for their purity. B cells were purified by using anti-CD19 immunomagnetic beads from human peripheral blood mononuclear cells (PBMC). Next, the activated B cells were treated in the presence or absence of coculture with CB-SC for 7 days before undergoing flow cytometry analysis of phenotypic change with different markers. RT-PCR was utilized to evaluate the levels of galectin expressions with or without treatment of activated B cells in order to find the key galectin contributing to the B-cell modulation.ResultsFlow cytometry demonstrated that the proliferation of activated B cells was markedly suppressed in the presence of CB-SC, leading to the down-regulation of immunoglobulin productions from the activated B cells. Phenotypic analysis revealed that treatment with CB-SC increased the percentage of IgD+CD27-naïve B cells, but decreased the percentage of IgD-CD27+switched B cells. Transwell assay showed that the immune suppression of CB-SC on B cells was dependent on the manner of cell-cell contact via Gal-9 molecule, as confirmed by the blocking experiment with the anti-Gal-9 monoclonal antibody. Mechanistic studies demonstrated that both calcium levels of cytoplasm and mitochondria were down-regulated after the treatment with CB-SC, causing the decline of mitochondrial membrane potential in the activated B cells. Western blot exhibited that the levels of phosphorylated Akt and Erk1/2 signaling proteins in the activated B cells were also markedly reduced in the presence of CB-SC.ConclusionsCB-SC displayed multiple immune modulations on B cells through the Gal-9-mediated cell-cell contact mechanism and calcium flux/Akt/Erk1/2 signaling pathways. The data advances current understanding about the molecular mechanisms underlying the Stem Cell Educator therapy to treat autoimmune diseases in clinics.
Pseudofinder: detection of pseudogenes in prokaryotic genomes
Authors: Syberg-Olsen Mitchell J. , Garber Arkadiy I. , Keeling Patrick J. , McCutcheon John P. , Husnik Filip 
Published: October 2021

AbstractProkaryotic genomes are generally gene dense and encode relatively few pseudogenes, or nonfunctional/inactivated remnants of genes. However, in certain contexts, such as recent ecological shifts or extreme population bottlenecks (such as those experienced by symbionts and pathogens), pseudogenes can quickly accumulate and form a substantial fraction of the genome. Identification of pseudogenes is, thus, a critical step for understanding the evolutionary forces acting upon, and the functional potential encoded within, prokaryotic genomes. Here, we present Pseudofinder, an open-source software dedicated to pseudogene identification and analysis. With Pseudofinder’s multi-pronged, reference-based approach, we demonstrate its capacity to detect a wide variety of pseudogenes, including those that are highly degraded and typically missed by gene-calling pipelines, as well newly formed pseudogenes, which can have only one or a few inactivating mutations. Additionally, Pseudofinder can detect intact genes undergoing relaxed selection, which may indicate incipient pseudogene formation. Implementation of Pseudofinder in annotation pipelines will not only clarify the functional potential of sequenced microbes, but will also generate novel insights and hypotheses regarding the evolutionary dynamics of bacterial and archaeal genomes.
Comprehensive antibody profiling of mRNA vaccination in children
Authors: Bartsch Yannic C , St Denis Kerri J , Kaplonek Paulina , Kang Jaewon , Lam Evan C. , Burns Madeleine D , Farkas Eva J , Davis Jameson P , Boribong Brittany P , Edlow Andrea G , Fasano Alessio , Shreffler Wayne , Zavadska Dace , Johnson Marina , Goldblatt David , Balazs Alejandro B , Yonker Lael M , Alter Galit 
Published: October 2021

AbstractWhile children have been largely spared from COVID-19 disease, the emergence of viral variants of concern (VOC) with increased transmissibility, combined with fluctuating mask mandates and school re-openings have led to increased infections and disease among children. Thus, there is an urgent need to roll out COVID-19 vaccines to children of all ages. However, whether children respond equivalently to adults to mRNA vaccines and whether dosing will elicit optimal immunity remains unclear. Given the recent announcement of incomplete immunity induced by the pediatric dose of the BNT162b2 vaccine in young children, here we aimed to deeply profile and compare the vaccine-induced humoral immune response in 6-11 year old children receiving the pediatric (50μg) or adult (100μg) dose of the mRNA-1273 vaccine compared to adults and naturally infected children or children that experienced multi inflammatory syndrome in children (MIS-C) for the first time. Children elicited an IgG dominant vaccine induced immune response, surpassing adults at a matched 100μg dose, but more variable immunity at a 50μg dose. Irrespective of titer, children generated antibodies with enhanced Fc-receptor binding capacity. Moreover, like adults, children generated cross-VOC humoral immunity, marked by a decline of omicron receptor binding domain-binding, but robustly preserved omicron Spike-receptor binding, with robustly preserved Fc-receptor binding capabilities, in a dose dependent manner. These data indicate that while both 50μg and 100μg of mRNA vaccination in children elicits robust cross-VOC antibody responses, 100ug of mRNA in children results in highly preserved omicron-specific functional humoral immunity.One-Sentence SummarymRNA vaccination elicits robust humoral immune responses to SARS-CoV-2 in children 6-11 years of age.
Longitudinal changes in home confinement and mental health implications: A 17-month follow-up study in England during the COVID-19 pandemic
Authors: Bu Feifei , Steptoe Andrew , Fancourt Daisy 
Published: October 2021

AbstractBackgroundThe COVID-19 pandemic has brought about significant behavioural changes, one of which is increased time spent at home. Although official lockdowns were typically short-term and allowed people to leave their homes for exercise and essential activities, some individuals did not leave their home for prolonged periods due to a range of factors including clinical vulnerability. This study aimed to explore longitudinal patterns of such ‘home confinement’ across different stages of the COVID-19 pandemic in the UK, and its associated predictors and mental health outcomes.MethodsData were from the UCL COVID -19 Social Study. The analytical sample consisted of 25,390 adults in England who were followed up for 17 months from March 2020 to July 2021. Data were analysed using growth mixture models.ResultsOur analyses identified three classes of growth trajectories, including one class showing a high level of persistent home confinement (24.8%), one changing class with clear alignment with national containment policy/advice (32.0%), and one class with a persistently low level of confinement (43.1%). A range of factors were found to be associated the class membership of home confinement trajectories, such as age, gender, income, employment status, social relationships and health. The class with a high level of confinement had the highest number of depressive and anxiety symptoms at the end of the follow-up independent of potential confounders.ConclusionsThere was substantial heterogeneity in longitudinal patterns of home confinement during the COVID-19 pandemic. However, a striking proportion of our sample maintained a high level of home confinement over the course of 17 months, even during periods when containment measures were eased or removed and when infection rates were low. They also had the worst mental health outcomes. This group warrants special attention in addressing the mental health impact of the COVID-19 pandemic.
Boston Cognitive Assessment (BOCA) — a comprehensive self-administered smartphone- and computer-based at-home test for longitudinal tracking of cognitive performance
Authors: Vyshedskiy Andrey , Netson Rebecca , Fridberg Elisabeth , Jagadeesan Priyanka , Arnold Matthew , Barnett Sophie , Gondalia Anjali , Maslova Victoria , deTorres Lauren , Ostrovsky Simone , Durakovic Danijel , Savchenko Andrei , McNett Sienna , Kogan Mikhail , Piryatinsky Irene , Gold Dov 
Published: October 2021

AbstractLongitudinal cognitive testing is essential for developing novel preventive interventions for dementia and Alzheimer’s disease; however, the few available tools have significant practice effect and depend on an external evaluator. We developed a self-administered 10-minute at-home test intended for longitudinal cognitive monitoring, Boston Cognitive Assessment or BOCA. The goal of this project was to validate BOCA. BOCA uses randomly selected non-repeating tasks to minimize practice effects. BOCA evaluates eight cognitive domains: 1) Memory/Immediate Recall, 2) Language Comprehension/Prefrontal Synthesis, 3) Visuospatial Reasoning / Mental rotation, 4) Executive function / Clock Test, 5) Attention, 6) Mental math, 7) Orientation, and 8) Memory/Delayed Recall. BOCA was administered to patients with cognitive impairment (n = 50) and age- and education-matched controls (n = 50). Test scores were significantly different between patients and controls (p < 0.001) suggesting good discriminative ability. The Cronbach’s alpha was 0.87 implying good internal consistency. BOCA demonstrated strong correlation with Montreal Cognitive Assessment (MOCA) (R= 0.90, p <0.001). The study revealed strong (R=0.94, p <0.001) test-retest reliability of the total BOCA score one week after participants’ initial administration. The practice effect tested by daily BOCA administration over 10 days was insignificant (β=0.03, p=0.74). BOCA has the potential to reduce the cost and improve the quality of longitudinal cognitive tracking essential for testing novel interventions designed to reduce or reverse cognitive aging. BOCA is available online gratis at www.bocatest.org.
CRISPR-Cas9-mediated knockout of CYP79D1 and CYP79D2 in cassava attenuates toxic cyanogen production
Authors: Gomez Michael A. , Berkoff Kodiak C. , Gill Baljeet K. , Iavarone Anthony T. , Lieberman Samantha E. , Ma Jessica M. , Schultink Alex , Wyman Stacia K. , Chauhan Raj Deepika , Taylor Nigel J. , Staskawicz Brian J. , Cho Myeong-Je , Rokhsar Daniel S. , Lyons Jessica B. 
Published: October 2021

SummaryCassava (Manihot esculenta Crantz) is a starchy root crop that supports over a billion people in tropical and subtropical regions of the world. This staple, however, produces toxic cyanogenic compounds and requires processing for safe consumption. Excessive consumption of insufficiently processed cassava, in combination with protein-poor diets, can have neurodegenerative impacts. Reducing the cyanogen content by conventional breeding is problematic due to the heterozygous nature of the crop; recombination will generally disrupt a clonally propagated cultivar’s suite of desirable traits. To reduce cyanide levels in cassava, we used CRISPR-mediated mutagenesis to disrupt the cytochrome P450 genes CYP79D1 and CYP79D2 whose protein products catalyze the first step in cyanogenic glucoside biosynthesis. Knockout of both genes eliminated cyanide in leaves and storage roots of cassava accession 60444 and the West African, farmer-preferred cultivar TME 419. Although knockout of CYP79D2 alone resulted in significant reduction of cyanide, mutagenesis of CYP79D1 did not, indicating these paralogs have diverged in their function. Our work demonstrates cassava genome editing for food safety, reduced processing requirements, and environmental benefits that could be readily extended to other farmer-preferred cultivars.
Activation of the essential kinase PDK1 by phosphoinositide-driven trans-autophosphorylation
Authors: Levina Aleksandra , Fleming Kaelin D. , Burke John E. , Leonard Thomas A. 
Published: October 2021

Abstract3-phosphoinositide-dependent kinase 1 (PDK1) is an essential serine/threonine protein kinase, which plays a crucial role in cell growth and proliferation. It is often referred to as a ‘master’ kinase due to its ability to activate at least 23 downstream protein kinases implicated in various signaling pathways. In this study, we have elucidated the mechanism of phosphoinositide-driven PDK1 auto-activation. We show that PDK1 trans- autophosphorylation is mediated by a PIP3-mediated face-to-face dimer. We report regulatory motifs in the kinase-PH interdomain linker that allosterically activate PDK1 autophosphorylation via a linker-swapped dimer mechanism. Finally, we show that PDK1 is autoinhibited by its PH domain and that positive cooperativity of PIP3binding drives switch- like activation of PDK1. Our work implies that the PDK1-mediated activation of effector kinases, including Akt, PKC, Sgk, S6K and RSK, many of whom are not directly regulated by phosphoinositides, is also likely to be dependent on PIP3or PI(3, 4)P2.
Impairment of the cellulose degradation machinery enhances fungal virulence but limits reproductive fitness
Authors: Gámez-Arjona Francisco M. , Vitale Stefania , Voxeur Aline , Dora Susanne , Müller Sascha , Sancho-Andrés Gloria , Montesinos Juan Carlos , Di Pietro Antonio , Sánchez-Rodríguez Clara 
Published: October 2021

AbstractFungal endophytes grow in the apoplastic space, in constant contact with the plant cell wall (CW) that hinders microbe progression, while representing a source of nutrients. Although numerous fungal CW modifying proteins have been identified, their role during host colonization remains underexplored. Here we show that the root-infecting plant pathogenFusarium oxysporum(Fo) does not require its complete arsenal of cellulases to infect the host plant. Quite the opposite, Fo mutants impaired in cellulose degradation become hypervirulent by enhancing the secretion of virulence factors. On the other hand, the reduction on cellulase activity had a severe negative effect on saprophytic growth and microconidia production during the final stages of the Fo infection cycle. These findings enhance our understanding on the function of plant CW degradation on the outcome of host-microbe interactions and reveal an unexpected role of cellulose degradation in a pathogen’s evolutionary success.TeaserUnexpectedly, fungi compromised in their capacity to degrade plant cellulose are hypervirulent but impaired in sporulation.
Analysis of DYRK1B, PPARG, and CEBPB Expression Patterns in Adipose-Derived Stem Cells from Patients carrying DYRK1B R102C and Healthy Individuals During Adipogenesis
Authors: Armanmehr Azam , Khamirani Hossein Jafari , Zoghi Sina , Dianatpour Mehdi 
Published: October 2021

AbstractBackgroundMetabolic syndrome (MetS) is a group of signs and symptoms that are associated with higher risk of Type 2 Diabetes Mellitus (T2DM) and Cardiovascular Diseases (CVDs). The major risk factor for developing MetS is abdominal obesity that is caused by increase in adipocyte size or number. Adipocyte number multiplication is caused by differentiation of mesenchymal stem cells into adipose tissue. Numerous studies have evaluated the expression of key transcription factors including PPARG and CEBPB during adipocyte differentiation in murine cells such as 3T3-L1 cell line. In order to comprehend the expression changes during the process of fat accumulation in adipose tissue derived stem cells (ASCs), we compared the expression of DYRK1B, PPARG, and CEBPB in undifferentiated and differentiated ASCs into mature adipocytes between the patient (harboring DYRK1b R102C) and control (healthy individuals) groups.MethodsGene expression was evaluated on eighth days pre-induction and day 1, 5 and 15 post-induction. The pluripotent capacity of ASCs and the potential for differentiation into adipocyte were confirmed by flow cytometry analysis of surface markers (CD34, CD44, CD105 and CD90), and Oil red O staining, respectively. Expression of DYRK1B, PPARG, and CEBPB were assessed by RT-PCR in patients’ and normal individuals’ samples.ResultsThe expression of DYRK1B kinase and transcription factors (CEBPB and PPARG) are significantly higher in adipose derived stem cells harboring DYRK1b R102C compared to non-carriers on day 5 and 15 during adipocyte differentiation. These proteins may be suitable targets for therapeutic strategies in obesity and obesity related disorders like metabolic syndrome. Furthermore, AZ191 exhibited a potent and selectively inhibitory activity toward DYRK1B and CEBPB.ConclusionCEBPB, PPARA and DYRK1B contribute to adipogenesis and the development of metabolic syndrome; thus, they can be harnessed in developing therapeutic agents against metabolic syndrome.