bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of Exosome Biogenesis Genes is Pervasively Altered by Aging in the Mouse and in the Human Brain During Alzheimer’s Disease
Authors: Lark Daniel S. , LaRocca Thomas J. 
Published: August 2021

AbstractExtracellular vesicles (EVs) like exosomes are secreted by numerous cell types in a variety of tissues. EVs have been implicated in both aging and age-related disorders like Alzheimer’s disease (AD). However, how aging and AD affect EV biogenesis within and across cell types is poorly understood. Moreover, cells acquire characteristics based on tissue niche, but the impact of tissue residence on cell type EV biogenesis is unknown.We explored theTabula Muris Senis, Mayo RNA-seq and ROSMAP data sets to characterize the cell and tissue-specific effects of aging and AD on genes involved in EV biogenesis. Specifically, we examined the age-dependent expression (age coefficient) of genes involved in EV biogenesis (22 genes), EV cargo (3 genes) and senescence (5 genes). Of the 131 cell populations (cell type x tissue) studied, 95 have at least one EV biogenesis gene impacted by age. The most common gene increased by age was charged multivesicular body protein 2A (CHMP2A) (54 cell populations). The most common gene decreased by age was syndecan binding protein (SDCBP) (58 cell populations). The senescence-associated genes cyclin-dependent kinase 1A (CDKN1A) and CDKN2A were not related to changes in CHMP2A and SDCBP and were altered by age in fewer cell populations. Finally, individuals with AD had decreased CHMP2A and increased SDCBP expression, opposite of what is observed with aging in the absence of diagnosed neurological disease. These findings indicate that age modifies exosome biogenesis gene expression in many cell populations mostly independent of senescence, and may be further altered in AD.
Genomic Basis of Multiple Myeloma Subtypes from the MMRF CoMMpass Study
Authors: Skerget Sheri , Penaherrera Daniel , Chari Ajai , Jagannath Sundar , Siegel David S. , Vij Ravi , Orloff Gregory , Jakubowiak Andrzej , Niesvizky Ruben , Liles Darla , Berdeja Jesus , Levy Moshe , Wolf Jeffrey , Usmani Saad Z. ,   The MMRF CoMMpass Network, Christofferson Austin W. , Nasser Sara , Aldrich Jessica L. , Legendre Christophe , Benard Brooks , Miller Chase , Turner Bryce , Kurdoglu Ahmet , Washington Megan , Yellapantula Venkata , Adkins Jonathan R. , Cuyugan Lori , Boateng Martin , Helland Adrienne , Kyman Shari , McDonald Jackie , Reiman Rebecca , Stephenson Kristi , Tassone Erica , Blanski Alex , Docter Brianne , Kirchhoff Meghan , Rohrer Daniel C. , D’Agostino Mattia , Gamella Manuela , Collison Kimberly , Stumph Jennifer , Kidd Pam , Donnelly Andrea , Zaugg Barbara , Toone Maureen , McBride Kyle , DeRome Mary , Yesil Jennifer , Craig David , Liang Winnie , Gutierrez Norma C. , Jewell Scott D. , Carpten John , Anderson Kenneth C. , Cho Hearn Jay , Auclair Daniel , Lonial Sagar , Keats Jonathan J. 
Published: August 2021

AbstractMultiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The MMRF CoMMpass study is a longitudinal, observational clinical study of newly diagnosed multiple myeloma patients where tumor samples are characterized using whole genome, exome, and RNA sequencing at diagnosis and progression, and clinical data is collected every three months. Analyses of the baseline cohort identified genes that are the target of recurrent gain- and loss-of-function events. Consensus clustering identified 8 and 12 unique copy number and expression subtypes of myeloma, respectively, identifying high- risk genetic subtypes and elucidating many of the molecular underpinnings of these unique biological groups. Analysis of serial samples showed 25.5% of patients transition to a high-risk expression subtype at progression. We observed robust expression of immunotherapy targets in this subtype, suggesting a potential therapeutic option.
Efficacy and safety of a drug-free, barrier-forming nasal spray for allergic rhinitis: randomized, open-label, crossover noninferiority trial
Authors: Nehrig Julian , Grosse Nicole , Hohenfeld Ilja P. , Fais Fabio , Meyer Thomas , Hohlfeld Jens M. , Badorrek Philipp 
Published: August 2021

AbstractBackgroundSymptoms of allergic rhinitis can be reduced by nonpharmacological nasal sprays that create a barrier between allergens and the nasal mucosa. A new nasal spray (AM-301) containing the clay mineral bentonite was tested for its ability to reduce symptoms to grass pollen.MethodsThis open label, crossover, noninferiority trial compared the efficacy and safety of AM-301 to that of hydroxypropyl methylcellulose (HPMC; Nasaleze Allergy Blocker), an established barrier method. Adults with seasonal allergic rhinitis were exposed to Dactylis glomerata pollen, in the Fraunhofer Allergen Challenge Chamber, first without protection and then protected by HPMC or AM-301 (7 days apart). Efficacy was assessed from total nasal symptom score (TNSS), nasal secretion weight, and subjective rating. The primary endpoint was the difference, between AM-301 and HPMC, in least square mean change in TNSS over a 4-hour exposure to allergen.ResultsThe study enrolled 36 persons, and 35 completed all study visits. The mean TNSS was 5.91 during unprotected exposure, 5.20 during protection with HPMC, and 4.82 during protection with AM-301. The difference in least square means between the two treatments was -0.39 (95% CI, -0.89 to 0.10), establishing the noninferiority of AM-301. No difference in mean weight of nasal secretions was observed between the treatments. Efficacy was rated as good or very good for AM-301 by 31% and for HPMC by 14% of subjects. 16 subjects reported adverse events with a relationship to AM-301 or HPMC; most adverse events were mild and none was serious.ConclusionsAM-301 demonstrated noninferiority towards HPMC in the primary endpoint and was perceived better in subjective secondary endpoints. Both barrier-forming products had a persisting protective effect over 4 hours and were safe.Trial registrationGerman Clinical Trial Register (DRKS00024356). EUDAMED (CIV-20-10-034870).
Multi-ancestry Multivariate Genome-Wide Analysis Highlights the Role of Common Genetic Variation in Cardiac Structure, Function, and Heart Failure-related Traits
Authors: Levin Michael G. , Tsao Noah L. , Bellomo Tiffany R. , Bone William P. , Aragam Krishna G. , Yang Yifan , Morley Michael P. , Burke Megan , Judy Renae L. , Arany Zoltan , Cappola Thomas P. , Day Sharlene M. , Ellinor Patrick T. , Margulies Kenneth B. , Voight Benjamin F. , Damrauer Scott M. 
Published: August 2021

ABSTRACTHeart failure (HF) is a leading cause of cardiovascular morbidity and mortality, yet the contribution of common genetic variation to HF risk has not been fully elucidated, particularly in comparison to other common cardiometabolic traits. We conducted a multi-ancestry genome-wide association study (GWAS) meta-analysis of all-cause HF including up to 56,722 HF cases and 1,133,054 controls, identifying 4 novel loci. We then performed a multi-ancestry multivariate association study of HF and related cardiac imaging endophenotypes, identifying 71 conditionally-independent variants, including 16 novel loci. Secondary colocalization and transcriptome-wide association analyses identified known and novel candidate cardiomyopathy genes, which were validated in gene-expression profiling of failing and healthy human hearts. Colocalization, gene expression profiling, and Mendelian randomization provided convergent evidence for the roles ofBCKDHAand circulating branch-chain amino acids in heart failure and cardiac structure. Finally, proteome-wide Mendelian randomization revealed 11 circulating proteins associated with HF or quantitative imaging traits. These analyses highlight similarities and differences among heart failure and associated cardiovascular imaging endophenotypes, implicate novel common genetic variation in the pathogenesis of HF, and identify circulating proteins that may represent novel cardiomyopathy treatment targets.
CAREGIVERS’ PERSPECTIVE: SATISFACTION WITH HEALTHCARE SERVICES AT THE PAEDIATRIC SPECIALIST CLINIC OF THE NATIONAL REFERRAL CENTRE IN MALAYSIA
Authors: Selvarajah Thinakaran , Yamamoto Eiko , Saw Yu Mon , Kariya Tetsuyoshi , Hamajima Nobuyuki 
Published: August 2021

ABSTRACTBackgroundThe idea of consumer satisfaction is gaining momentum across all business sectors around the world and a satisfaction survey is utilized as an instrument to recognize deficiencies with various facets of services and offers a valuable opportunity for customers to evaluate their experience with healthcare services. A first research performed at a public hospital’s paediatric clinic, which is also the first hospital to adopt the Public-Private-Partnership (PPP) model under the Ministry of Health Malaysia (MoH), with the aim of discovering prevalence and factors affecting the satisfaction of caregivers at the national referral centre.Materials and MethodsCross-sectional research using the standard self-administered SERVQUAL questionnaire was conducted amongst caregivers accompanying their child to the clinic. It consists of 16 paired statements to evaluate their expectations and experiences with the clinic services. 459 caregivers were involved with a majority being satisfied with the clinic services.ResultThe most significant dimensions were “tangibles”, “assurance” and “outcome”. Caregivers from the Indian community, lower household income, and lower educational background demonstrated a higher level of satisfaction.ConclusionThis article suggests that although most caregivers are very satisfied with the services, greater emphasis must be placed on delivering reliable service in response to MoH’s mission to provide quality and integrated people-centred health services in Malaysia.
Effect of laser assisted local anesthesia in single-visit root canal treatment for mandibular molar teeth with acute irreversible pulpitis
Authors: Subashri V , Nivedha V , Sherwood Anand , Abbott Paul V , Gutmann James L , Endo Cert , Farooq Omar , Aarthi MV 
Published: August 2021

AbstractPresent study evaluated the efficacy of laser activation to control intra- and post-operative pain in single-visit root treatment for mandibular molar teeth with acute irreversible pulpitis following 2% lignocaine inferior alveolar nerve block. Ninety-eight patients presenting with pain were randomly divided into two anesthetic groups. Group-I inferior alveolar nerve block plus buccal infiltration and intra-ligamentary injections, Group-II inferior alveolar nerve block followed by laser irradiation focused directly on the pulp tissue. Intra- and post-operative pain intensities were assessed on a 10-point scale.The mean intra-operative pain scores in group-I was 6.62 ± 1.6 and in group-II before and after laser irradiation pain scores was 6.94 ± 2.1 and 1.3 ± 2.04, respectively. Post-operative pain scores at 24-hrs in the laser group were significantly higher. Laser irradiation applied directly on pulp tissue for control of intra-operative pain was effective, thereby negating the need for additional local anesthesia.Clinical relevanceLaser activation was effective method to control intra-operative pain in irreversibly inflamed pulp.Laser irradiation did not cause adverse post-operative pain.
First observation of Aedes albopictus in the Tshuapa province (Boende) of the Democratic Republic of the Congo
Authors: Mariën Joachim , Laurent Nicolas , Smitz Nathalie , Gombeer Sophie 
Published: August 2021

AbstractIn May-June 2021, we detected Aedes albopictus adults near the central hospital in Boende, the capital city of the Tshuapa province of the Democratic Republic of the Congo (DRC). We identified the mosquitoes using morphological and molecular techniques (COI barcoding). This is the first report of this species in the DRC outside of Kinshasa and Kongo Central. Given the central location of Boende in the Congo Basin, our finding suggests that the vector might also have spread to other cities which are located upstream of the Congo River and its major tributaries. Because Aedes albopictus is an important vector for human arbovirus transmission, we highlight the need to investigate its distribution range and to update disease risk maps in Central Africa.
Opposite effects of nutrient enrichment and herbivory by an alien snail on growth of an invasive macrophyte and native macrophytes
Authors: Yan Yimin , Oduor Ayub M.O. , Li Feng , Xie Yonghong , Liu Yanjie 
Published: August 2021

AbstractHuman-mediated introduction of plant and animal species into biogeographic ranges where they did not occur before has been so pervasive globally that many ecosystems are now co-invaded by multiple alien plant and animal species. Although empirical evidence of invaders modifying recipient ecosystems to the benefit of other aliens is accumulating, these interactions remain underexplored and underrepresented in heuristic models of invasion success. Many freshwater ecosystems are co-invaded by aquatic macrophytes and mollusks and at the same time experience nutrient enrichment from various sources. However, studies are lacking that test how nutrient enrichment and co-invasion by alien herbivores and plant species can interactively affect native plant communities in aquatic habitats. To test such effects, we performed a freshwater mesocosm experiment in which we grew a synthetic native macrophyte community of three species under two levels of nutrient enrichment (enrichment vs. no-enrichment) treatment and fully crossed with two levels of competition from an invasive macrophyte Myriophyllum aquaticum (competition vs. no-competition), and two levels of herbivory by an invasive snail Pomacea canaliculata (herbivory vs. no-herbivory) treatments. Results show that herbivory by the invasive snail enhanced above-ground biomass yield of the invasive macrophyte. Moreover, the invasive herbivore preferentially fed on biomass of the native macrophytes over that of the invasive macrophyte. However, nutrient enrichment reduced above-ground biomass yield of the invasive macrophyte. Our results suggest that eutrophication of aquatic habitats that are already invaded by M. aquaticum may slow down invasive spread of the invasive macrophyte. However, herbivory by the invasive snail P. canaliculata may enhance invasive spread of M. aquaticum in the same habitats. Broadly, our study underscores the significance of considering several factors and their interaction when assessing the impact of invasive species, especially considering that many habitats experience co-invasion by plants and herbivores and simultaneously undergo varous other disturbances including nutrient enrichment.
Effect of EMS induced mutation in rice cultivar Nagina 22 on salinity tolerance
Authors: Shankar Arun , Choudhary OP , Bhatia Dharminder , Kuldeep-Singh  
Published: August 2021

AbstractSalinized hydroponic culture experiment with three salinity levels (EC control, 6 and 12 dS/m) was performed to screen salt tolerant mutants of aerobic rice cultivar Nagina 22 and to study the nature of salt tolerance from a total of 432 EMS induced M4 mutants. Plants were harvested 30 days after sowing. Growth parameters viz. root weight, shoot weight, root length, shoot length, Na and K concentrations in shoot and roots were measured. Combined Factor scores of growth parameters was computed by Principle Component Analysis using Minitab software.At EC 12 dS/m 10 mutants out of 432 were able to survive. At moderate salinity, some mutant lines produced higher shoot weight compared to their respective control showing inverse trend and the effectiveness of EMS induced mutation in inducing salinity tolerance to these mutants. At high salinity only10 mutants survived (remained green) up to the time of 30 days harvest. These mutants performed well in terms of overall growth recording 2.1-2.5 times higher factor score and 8-14 times higher shoot weight compared to the N 22 check. One mutant N22-L-1010 almost completely excluded Na at xylem parenchyma level. Two other mutants N22-L-1013 and N22-L-806 maintained Na exclusion compared to the N22 check. N22 check and mutant N22-L-1009 maintained similar degree of Na exclusion though the N22 check died because it cannot maintain adequate K in shoot.We conclude that EMS has induced salinity tolerance in some mutants. The study can be advanced further to characterize the putative mutants through molecular genetics approaches.
A comparison of data integration methods for single-cell RNA sequencing of cancer samples
Authors: Richards Laura M. , Riverin Mazdak , Mohanraj Suluxan , Ayyadhury Shamini , Croucher Danielle C. , Díaz-Mejía J. Javier , Coutinho Fiona J. , Dirks Peter B. , Pugh Trevor J. 
Published: August 2021

ABSTRACTTumours are routinely profiled with single-cell RNA sequencing (scRNA-seq) to characterize their diverse cellular ecosystems of malignant, immune, and stromal cell types. When combining data from multiple samples or studies, batch-specific technical variation can confound biological signals. However, scRNA-seq batch integration methods are often not designed for, or benchmarked, on datasets containing cancer cells. Here, we compare 5 data integration tools applied to 171,206 cells from 5 tumour scRNA-seq datasets. Based on our results, STACAS and fastMNN are the most suitable methods for integrating tumour datasets, demonstrating robust batch effect correction while preserving relevant biological variability in the malignant compartment. This comparison provides a framework for evaluating how well single-cell integration methods correct for technical variability while preserving biological heterogeneity of malignant and non-malignant cell populations.
Relative model selection of evolutionary substitution models can be sensitive to multiple sequence alignment uncertainty
Authors: Spielman Stephanie J. , Miraglia Molly L. 
Published: August 2021

AbstractBackgroundMultiple sequence alignments (MSAs) represent the fundamental unit of data inputted to most comparative sequence analyses. In phylogenetic analyses in particular, errors in MSA construction have the potential to induce further errors in downstream analyses such as phylogenetic reconstruction itself, ancestral state reconstruction, and divergence time estimation. In addition to providing phylogenetic methods with an MSA to analyze, researchers must also specify a suitable evolutionary model for the given analysis. Most commonly, researchers apply relative model selection to select a model from candidate set and then provide both the MSA and the selected model as input to subsequent analyses. While the influence of MSA errors has been explored for most stages of phylogenetics pipelines, the potential effects of MSA uncertainty on the relative model selection procedure itself have not been explored.ResultsWe assessed the consistency of relative model selection when presented with multiple perturbed versions of a given MSA. We find that while relative model selection is mostly robust to MSA uncertainty, in a substantial proportion of circumstances, relative model selection identifies distinct best-fitting models from different MSAs created from the same set of sequences. We find that this issue is more pervasive for nucleotide data compared to amino-acid data. However, we also find that it is challenging to predict whether relative model selection will be robust or sensitive to uncertainty in a given MSA.ConclusionsWe find that that MSA uncertainty can affect virtually all steps of phylogenetic analysis pipelines to a greater extent than has previously been recognized, including relative model selection.
Ribosome elongation kinetics of consecutively charged residues are coupled to electrostatic force
Authors: Leininger Sarah E. , Rodriguez Judith , Vu Quyen V. , Jiang Yang , Li Mai Suan , Deutsch Carol , O’Brien Edward P. 
Published: August 2021

AbstractThe speed of protein synthesis can dramatically change when consecutively charged residues are incorporated into an elongating nascent protein by the ribosome. The molecular origins of this class of allosteric coupling remain unknown. We demonstrate, using multi-scale simulations, that positively charged residues generate large forces that pull the P-site amino acid away from the A-site amino acid. Negatively charged residues generate forces of similar magnitude but opposite direction. And that these conformational changes, respectively, raise and lower the transition state barrier height to peptide bond formation, explaining how charged residues mechanochemically alter translation speed. This mechanochemical mechanism is consistent within vivoribosome profiling data exhibiting a proportionality between translation speed and the number of charged residues, experimental data characterizing nascent chain conformations, and a previously published cryo-EM structure of a ribosome-nascent chain complex containing consecutive lysines. These results expand the role of mechanochemistry in translation, and provide a framework for interpreting experimental results on translation speed.Abstract FigureFor table of contents use only.
Entamoeba histolyticadevelops resistance to complement deposition and lysis after acquisition of human complement regulatory proteins through trogocytosis
Authors: Miller Hannah W. , Tam Tammie S.Y. , Ralston Katherine S. 
Published: August 2021

ABSTRACTEntamoeba histolyticais the cause of amoebiasis. The trophozoite (amoeba) form of this parasite is capable of invading the intestine, and can disseminate through the bloodstream to other organs. The mechanisms that allow amoebae to evade complement deposition during dissemination have not been well characterized. We previously discovered a novel complement-evasion mechanism employed byE. histolytica.E. histolyticaingests small bites of living human cells in a process termed trogocytosis. We demonstrated that amoebae were protected from lysis by human serum following trogocytosis of human cells, and that amoebae acquired and displayed human membrane proteins from the cells they ingested. Here, we aimed to define how amoebae are protected from complement lysis after performing trogocytosis. We found that amoebae were protected from complement lysis after ingestion of both human Jurkat T cells and red blood cells, and that the level of protection correlated with the amount of material ingested. Trogocytosis of human cells led to a reduction in deposition of C3b on the surface of amoebae. We asked whether display of human complement regulators is involved in amoebic protection, and found that CD59 was displayed by amoebae after trogocytosis. Deletion of a single complement regulatory protein, CD59 or CD46, from Jurkat cells was not sufficient to alter amoebic protection from lysis, suggesting that multiple, redundant complement regulators mediate amoebic protection. However, exogeneous expression of CD46 or CD55 in amoebae was sufficient to confer protection from lysis. These studies shed light on a novel strategy for immune evasion by a pathogen.IMPORTANCEEntamoeba histolyticais the cause of amoebiasis, a diarrheal disease of global importance. While infection is often asymptomatic, the trophozoite (amoeba) form of this parasite is capable of invading and ulcerating the intestine, and can disseminate through the bloodstream to other organs. Understanding howE. histolyticaevades the complement system during dissemination is of great interest. Here we demonstrate for the first time that amoebae that have performed trogocytosis (nibbling of human cells) resist deposition of the complement protein C3b. Amoebae that have performed trogocytosis display the complement regulatory protein CD59. Overall, our studies suggest that acquisition and display of multiple, redundant complement regulators is involved in amoebic protection from complement lysis. These findings shed light on a novel strategy for immune evasion by a pathogen. Since other parasites use trogocytosis for cell killing, our findings may apply to the pathogenesis of other infections.