bluuebunny/crossref_metadata_2025_split huggingface dataset:
Syngeneic model of carcinogen-induced tumor mimics basal/squamous, stromal-rich, and neuroendocrine molecular and immunological features of muscle-invasive bladder cancer
Authors: Shah Shruti D , Gillard Bryan M , Wrobel Michelle M , Karasik Ellen , Moser Michael T , Mastri Michalis , Sule Norbert , Brackett Craig M , Huss Wendy J , Foster Barbara A 
Published: December 2022

AbstractBackgroundBladder cancer is a heterogenous disease and the emerging knowledge on molecular classification of bladder tumors could have impact to drive treatment decisions based on molecular subtype. Pre-clinical models representing each subtype are needed to test novel therapies. Carcinogen-induced bladder cancer models represent heterogeneous, immune-competent, pre-clinical testing options with many features found in the human disease.MethodsInvasive bladder tumors were induced in C57BL/6 mice when continuously exposed to N-butyl-N-(4-hydroxbutyl nitrosamine) (BBN) in the drinking water. Tumors were excised and serially passed by subcutaneous implantation into sex-matched syngeneic C57BL/6 hosts. Eight tumor lines were developed and named BBN-induced Urothelium Roswell Park (BURP) tumor lines. The BURP lines were characterized by applying consensus molecular classification to RNA expression, histopathology, and immune profiles by CIBERSORT. Two lines were further characterized for cisplatin response.ResultsEight BURP tumor lines were established with 3 male and 3 female BURP tumor lines, having the basal/squamous (BaSq) molecular phenotype and morphology. BURP-16SR was established from a male mouse and has a stromal-rich (SR) molecular phenotype and a sarcomatoid carcinoma morphology. BURP-19NE was established from a male mouse and has a neuroendocrine (NE)-like molecular phenotype and poorly differentiated morphology. The established BURP tumor lines have unique immune profiles with fewer immune infiltrates compared to their originating BBN-induced tumors. The immune profiles of the BURP tumor lines capture some of the features observed in the molecular classifications of human bladder cancer. BURP-16SR growth was inhibited by cisplatin treatment, while BURP-24BaSq did not respond to cisplatin.ConclusionsThe BURP tumor lines represent several molecular classifications, including basal/squamous, stroma-rich, and NE-like. The stroma-rich (BURP-16SR) and NE-like (BURP-19NE) represent unique immunocompetent models that can be used to test novel treatments in these less common bladder cancer subtypes. Six basal/squamous tumor lines were established from both male and female mice. Overall, the BURP tumor lines have less heterogeneity than the carcinogen-induced tumors and can be used to evaluate treatment response without the confounding mixed response often observed in heterogeneous tumors. Additionally, basal/squamous tumor lines were established and maintained in both male and female mice, thereby allowing these tumor lines to be used to compare differential treatment responses between sexes.
Ascending and Descending Aortic ECM Hydrogels for Modeling Aortic Wall Biology
Authors: Lee Yoojin C. , Richards Tara D. , Fantini Dalia A. , Kaczorowski David J. , Brown Bryan N. , Phillippi Julie A. 
Published: December 2022

ABSTRACTAlthoughin vitromodeling systems are becoming increasingly advanced, the complex pathophysiology of aortic diseases remains a challenge to mimic and adequately replicate. Biomechanical weakening of the vessel wall, medial degeneration and remodeling are all hallmarks of aneurysmal diseases via incompletely understood mechanisms. Understanding what factors disrupt the multi-layer biology of large blood vessels during the progression of aneurysmal disease can aid in the unmet clinical need to slow or halt disease progression. In particular, the microvascular network of the vasa vasorum provides the primary blood supply to the outer aortic wall and is a key component of inter-layer vascular health. Different origins of the vasa vasorum correspond to the anatomically specific functions of the aortic regions, which can further pertain to the differing origins of vascular wall cells and putative differences in the composition of extracellular matrix (ECM). Biologic scaffolds produced from ECM are useful biomaterials to understand biological processes and address wound healing, stem cell differentiation, and angiogenesis for bothin vitroandin vivodisease models. In the present study, we investigated putative differences in composition and structure between ascending and descending aorta-derived ECM to better understand intra- and inter-layer cell-matrix interactions relevant to vasa vasorum function in the aorta. Ascending and descending aortic ECM (AECM) hydrogels were shown to retain bioactivity and influence contractility of human vasa vasorum-associated pericytes. A comprehensive understanding of the effect of layer-specific ECM on cells in different aortic regions could help uncover novel disease mechanisms.
Molecular basis of interactions between CaMKII and α-actinin-2 that underlie dendritic spine enlargement
Authors: Curtis Ashton J. , Zhu Jian , Penny Christopher J. , Gold Matthew G. 
Published: December 2022

AbstractCa2+/calmodulin-dependent protein kinase II (CaMKII) is essential for long-term potentiation (LTP) of excitatory synapses that is linked to learning and memory. In this study, we focused on understanding how interactions between CaMKIIα and the actin crosslinking protein α-actinin-2 underlie long-lasting changes in dendritic spine architecture. We found that association of the two proteins was unexpectedly elevated following stimulation of NMDA receptors to trigger structural LTP in primary hippocampal neurons. Furthermore, disruption of interactions between the two proteins prevented the accumulation of enlarged mushroom-type dendritic spines following NMDA receptor activation. α-actinin-2 binds to the regulatory segment of CaMKII. Calorimetry experiments, and a crystal structure of α-actinin-2 EF hands 3 and 4 in complex with the CaMKII regulatory segment, indicate that the regulatory segment of autoinhibited CaMKII is not fully accessible to α-actinin-2. Pull-down experiments show that occupation of the CaMKII substrate binding groove by GluN2B markedly increases α-actinin-2 access to the CaMKII regulatory segment. Overall, our study provides new mechanistic insight into the molecular basis of structural LTP and reveals an added layer of sophistication to the function of CaMKII.
A NOVEL METHOD FOR BLOOD DETECTION USING FLUORESCENT DYE
Authors: Vajpayee Kamayani , Desai Preet , Dash Hirak Ranjan , Shukla Ritesh Kumar 
Published: December 2022

AbstractDetection of the body fluid present at a crime scene is essential for any forensic investigation. Amongst all the body fluids (sweat, semen, vaginal fluid, saliva, etc.,) blood is the most frequently encountered evidence at the crime scene. Currently, reagents like benzidine, orthotoluidine, tetramethylbenzidine, phenolphthalein, leucomalachite green, luminol, and fluorescein are used to screen the presence of blood on different surfaces (porous/nonporous). Majority of these tests are based on colorimetric changes owing to the nature of hemoglobin to catalyze the oxidation of chromogenic compounds. Apart from aiding the investigation, these reagents show toxic behavior (DNA damage, carcinogenic, etc.) and false-positive results. Hence, to circumvent this issue, the present study attempts to develop a state-of-art methodology for preliminary blood detection and screening using fluorescein-derived 2’,7’-dichlorofluorescein di-acetate (DCFDA) dye. It is hereby proposed that the fluorescein-based dye can successfully detect blood and bloodstains aged up to 20 days. Moreover, supplemental experiments have suggested that the dye doesn’t interfere with DNA integritycausing any damage to DNA. Parallelly, no false-positive reactions have been observed as tested against similar-looking substances.
White Matter microstructure effect in ADHD: a two-sample mendelian randomization study
Authors: Tavares Maria Eduarda de Araujo , Carpena Marina Xavier , Vitola Eduardo Schneider , Bandeira Cibele Edom , Cupertino Renata Basso , Colbeich Eduarda , da Cunha Pamela Ferreira , Rovaris Diego Luiz , Grevet Eugenio Horacio , da Silva Bruna Santos , Bau Claiton Henrique Dotto 
Published: December 2022

AbstractIntroductionGenome Wide Association Studies (GWAS) revealed the highly polygenic architecture of Attention-Deficit/Hyperactivity Disorder (ADHD) and highlighted the contribution of common variants related to brain development and function. In parallel, several imaging studies attempted to discover disorder-related brain structures, with some significant findings concerning white matter. Two-sample mendelian randomization (2SMR) is a powerful tool to evaluate causality between two phenotypes using summary statistics data. We aimed to investigate a possible causal relationship between white matter genetically predicted variation and ADHD diagnosis through 2SMR.MethodsA unidirectional two-sample MR analysis was performed based on summary statistics of GWAS between 22 different white matter (WM) mean fractional anisotropy measures and ADHD. We used 4 different MR approaches, considering IVW random effects as the main analysis, followed by several sensitivity analyses. Linkage Disequilibrium Score Regression (LDSC) was evaluated in the same set of samples to corroborate the direction of associations.Results and DiscussionOur most consistent finding across MR and LDSC approach, following the sensitivity analyses, indicate that the decreased WM microstructure integrity of the fornix stria terminalis (FXSTivwbeta:-0.266 SE:0.083 pFDR:0.021) genetic liability has a causal influence on ADHD diagnosis. The FXST is formed by connection fibers inside the limbic system, which is crucial to emotional processing, learning, and memory, functions usually impaired in ADHD. Therefore, this study increases knowledge concerning ADHD neurobiology and provides novel evidence of the causal effect of WM integrity in the limbic system, which could contribute to the advances in additional diagnostic tools as well as pharmacological brain structure targets.
Early and late onset preeclampsia associated with different placental pathology and clinical risk characteristics
Authors: Zhang Peilin , Shama Naureen 
Published: December 2022

AbstractBackgroundPreeclampsia is classified as early onset and late onset types with different clinical manifestation and pathogenesis. Placental pathology of preeclampsia has been largely based on description of the early onset type, and the morphologic features of placenta from late onset preeclampsia were similar to those of non-preeclamptic placentas.ObjectiveTo identify clinically relevant maternal and neonatal risk characteristics and placental pathology for early onset and late onset preeclampsia.Study designWe have collected all placental pathology information as well as maternal and neonatal birth information from March 2020 to December 2021 including preeclampsia and non-preeclampsia patients. We compared preterm and term preeclampsia in regards to maternal and neonatal complication and placental pathology by using logistic regression models to determine the important clinical risk factors associated with preeclampsia and placental pathology.ResultsA total 3724 placentas including 614 placentas from preeclamptic and 3110 non-preeclamptic patients were studied. Preterm preeclampsia (<37 weeks) was similar to early onset preeclampsia (<34 weeks) in maternal and neonatal complications as well as placental pathology, and these features were statistically different from those from term preeclampsia. More male fetuses were associated with early onset preeclampsia and female fetuses associated with late onset term preeclampsia when compared to non-preeclamptic patients. Maternal race/ethnicity and marital status were associated with preeclampsia but this association was no longer significant after logistic regression analysis. Preterm preeclampsia was statistically associated with gestational diabetes, placental infarcts, intrauterine fetal growth restriction and fetal vascular malperfusion, whereas term preeclampsia was associated with decidual vasculopathy and maternal obesity.ConclusionsEarly onset preeclampsia is a different clinical syndrome from the late onset type with clinical implication of pathogenesis and management.
Condom use and HIV testing among adults in Switzerland: repeated national cross-sectional surveys 2007, 2012, and 2017
Authors: Buitrago-Garcia Diana , Salanti Georgia , Low Nicola 
Published: December 2022

AbstractBackgroundMonitoring of HIV and sexually transmitted infection (STI) prevention is important for guiding national sexual health programmes for both the general population and key populations. The objectives of this study were to examine patterns of condom use at last intercourse and lifetime HIV testing from 2007 to 2017 in Switzerland, and to explore factors associated with these behaviours in men and women with opposite-sex partners and with same sex partners.MethodsWe analysed data from the 2007, 2012 and 2017 Swiss Health Survey. At each time point, outcome and population group, we conducted a descriptive analysis of weighted data and conducted multivariable logistic regression to obtain adjusted odds ratios (aOR) with 95% confidence intervals (CI) and compared outcomes between the timepoints.ResultsIn total, 43,949 people were interviewed: 21,274 men and 22,675 women, who reported having sex only with partners of the opposite sex, 633 men who reported sex with a male partner and 699 women who reported sex with a female partner. Among the three surveys the prevalence of condom use varied from 24 to 26% of men and 18 to 21% in women with only opposite-sex partners (aOR men, 0.93, 95% CI 0.82, 1.06; women 0.98, 95% CI 0.86 to 1.11). In men with any same sex partner the prevalence of condom use increased from 43% in 2007 to 54% in 2017 (aOR 1.80, 95% CI 0.97, 3.34). In multivariable analysis, the factor most strongly associated with condom use was sex with an occasional partner at last intercourse. HIV testing ever increased across all three survey years in all groups: 2017 vs. 2007, aOR men with only opposite-sex partners 1.57 (95% CI 1.42, 1.74), women with only opposite-sex partners 1.54 (1.39, 1.71), men with any same sex partner 1.85 (0.96, 3.55), women with any same sex partner 1.31 (0.74, 2.30).ConclusionsMonitoring of condom use, and HIV testing should continue and contribute to the development of the national sexual health programme. Stronger promotion of condoms for people with opposite-sex partners might be needed, since overall condom use at last intercourse has not changed since 2007.
Assessment of Environmental Factors Associated with Antibiotic Resistance Genes (ARGs) in the Yangtze Delta, China
Authors: Miao Jiazheng , Ling Yikai , Chen Xiaoyuan , Wu Siyuan , Umar Sajid , Xu Shixin , Anderson Benjamin D. 
Published: December 2022

AbstractThe emergence of antimicrobial resistance (AMR) is an urgent and complex public health challenge worldwide. As a sub-problem of AMR, antibacterial resistance (ABR) is of particular concern due to inadequacy of alternative medication. Earlier studies have shown that ABR is not only impacted by antibiotics, but also affected by the interactions between bacteria and their environments. Therefore, to combat ABR in a specific region, local environmental conditions must be investigated to comprehensively understand which environmental factors might contribute to ABR and propose more tailored solutions. This study surveyed environmental contributors of antibiotic resistance genes (ARGs), the parameter for measuring ABR, in the Yangtze Delta. A high abundance of ARGs was detected, despite low antibiotic and heavy metal concentrations. Phosphorus, chromium, manganese, calcium, and strontium were identified as potential key contributors of ARGs. Suppression of ARGs could be realized through decreasing the concentration of phosphorus in surface water. Group 2A light metals (e.g., magnesium and calcium) could be developed as eco-friendly reagents for controlling antibiotic resistance in the future.
IKBKB reduces huntingtin aggregation by phosphorylating Serine 13 via a non-canonical IKK pathway
Authors: Cariulo Cristina , Martufi Paola , Verani Margherita , Toledo-Sherman Leticia , Lee Ramee , Dominguez Celia , Petricca Lara , Caricasole Andrea 
Published: December 2022

AbstractN-terminal phosphorylation at residues T3 and S13 is believed to have important beneficial implications for the biological and pathological properties of mutant huntingtin, where IKBKB was identified as a candidate regulator of huntingtin N-terminal phosphorylation. The paucity of mechanistic information on IKK pathways, together with the lack of sensitive methods to quantify endogenous huntingtin phosphorylation, prevented detailed study of the role of IKBKB in Huntington’s disease. Using novel ultrasensitive assays, we demonstrate that IKBKB can regulate endogenous S13 huntingtin phosphorylation in a manner dependent on its kinase activity and known regulators. We found that the ability of IKBKB to phosphorylate endogenous huntingtin S13 is mediated through a non-canonical IRF3-mediated IKK-pathway, distinct from the established involvement of IKBKB in mutant huntingtin’s pathological mechanisms mediated via the canonical pathway. Furthermore, increased huntingtin S13 phosphorylation by IKBKB resulted in decreased aggregation of mutant huntingtin in cells, again dependent on its kinase activity. These findings point to a non-canonical IKK-pathway linking S13 huntingtin phosphorylation to the pathological properties of mutant huntingtin aggregation, thought to be significant to Huntington’s disease.
Cis-regulatory evolution of the potassium channel genekcnj13during pigment pattern diversification inDaniofish
Authors: Podobnik Marco , Singh Ajeet P. , Fu Zhenqiang , Dooley Christopher M. , Frohnhöfer Hans Georg , Firlej Magdalena , Elhabashy Hadeer , Weyand Simone , Weir John R. , Lu Jianguo , Nüsslein-Volhard Christiane , Irion Uwe 
Published: December 2022

AbstractTeleost fish of the genusDanioare excellent models to study the genetic and cellular bases of pigment pattern variation in vertebrates. The two sister speciesDanio rerioandDanio aesculapiishow divergent patterns of horizontal stripes and vertical bars that are partly caused by the evolution of the potassium channel genekcnj13. InD. rerio, kcnj13is required in melanophores for interactions with xanthophores and iridophores, which cause location-specific pigment cell shapes and thereby influence colour pattern and contrast. Here, we show that cis-regulatory rather than protein coding changes underliekcnj13evolution between the two species.D. aesculapiiexpress lowerkcnj13levels and exhibit low-contrast patterns similar toD. reriomutants. Our results suggest that homotypic and heterotypic interactions between the pigment cells and their shapes diverged between species by quantitative changes inkcnj13expression during pigment pattern diversification.
Hepatitis E virus genome replication is independent of cyclophilins A and B
Authors: Buchanan Frazer J.T. , Chen Shucheng , Harris Mark , Herod Morgan R. 
Published: December 2022

AbstractHepatitis E virus (HEV) is an emerging pathogen responsible for more than 20 million cases of acute hepatitis globally per annum. Healthy individuals typically have a self-limiting infection, however, mortality rates in some populations such as pregnant women can reach 30%. A detailed understanding of the virus lifecycle is lacking, mainly due to limitations in experimental systems. In this regard, the cyclophilins are an important family of proteins that have peptidyl-prolyl isomerase activity and play roles in the replication of a number of positive-sense RNA viruses, including hepatotropic viruses such as hepatitis C virus (HCV). Cyclophilin A (CypA) and cyclophilin B (CypB) are the two most abundant human cyclophilins in hepatocytes and are therefore potential targets for pan-viral therapeutics. Here, we investigated the importance of CypA and CypB for HEV genome replication using a sub-genomic replicon system. This system removes the requirements for viral entry and packaging and therefore allows for the sensitive measurement of viral genome replication in isolation. Using pharmacological inhibition by cyclosporine A (CsA), known to suppress HCV replication, and silencing by shRNA we find that CypA and CypB are not essential for replication of genotype 1 or 3 HEV replication. However, we find that silencing of CypB reduces replication of genotype 1 HEV in some cells, but not genotype 3. These data suggests HEV is atypical in its requirements for cyclophilin for viral genome replication and that this phenomenon could be genotype specific.
MADS31 supports female germline development by repressing the post-fertilization program in cereal ovules
Authors: Yang Xiujuan , Li Gang , Shi Jin , Wilkinson Laura G. , Aubert Matthew K. , Houston Kelly , Shirley Neil J. , Colombo Lucia , Tucker Matthew R. 
Published: December 2022

AbstractThe female germline of flowering plants develops within a niche of somatic ovule cells, also referred to as the nucellus. How niche cells maintain their own somatic developmental program, yet support the development of adjoining germline cells, remains largely unknown. Here we report that MADS31, a conserved MADS-box transcription factor from the B-sister subclass, is a potent regulator of niche cell identity in barley. MADS31 is preferentially expressed in nucellar cells directly adjoining the germline, and loss-of-functionmads31mutants exhibit deformed and disorganized nucellar cells, leading to impaired germline development and partial female sterility. Molecular assays indicate that MADS31 encodes a potent transcriptional repressor, repressing genes in the ovule that are normally active in the seed. One prominent target of MADS31 isNRPD4b, a seed-expressed component of RNA polymerase IV/V that is involved in gene silencing via RNA directed DNA methylation.NRPD4bis directly repressed by MADS31in vivoand is de-repressed inmads31ovules, while overexpression ofNRPD4brecapitulates themads31ovule phenotype. This coincides with specific changes in histone methylation and is consistent withNRPD4bbeing directly repressed by MADS31 to maintain ovule niche functionality. Our findings reveal a new mechanism by which somatic ovule tissues maintain their own identity before transitioning to the post-fertilization program.