bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual Versus Single Oxygenated Hypothermic Machine Perfusion of Porcine Livers: Impact on Hepatobiliary and Endothelial Cell Injury
Authors: de Vries Yvonne , Brüggenwirth Isabel M. A. , Karangwa Shanice A. , von Meijenfeldt Fien A. , van Leeuwen Otto B. , Burlage Laura C. , de Jong Iris E. M. , Gouw Annette S. H. , de Meijer Vincent E. , Lisman Ton , Porte Robert J.
Published: August 2021

Background.

Hypothermic oxygenated machine perfusion (HOPE) reduces ischemia-reperfusion injury of donor livers and is increasingly used in clinical transplantation. However, it remains unclear whether perfusion via the portal vein alone (HOPE) or via both the portal vein and hepatic artery (dual HOPE or DHOPE) is superior.

Methods.

Twelve porcine livers donated after circulatory death were randomized for 2 h of HOPE (n = 6) or DHOPE (n = 6), followed by 4 h of warm reperfusion with whole blood, to mimic transplantation. Hepatobiliary and endothelial cell function and injury markers were determined in perfusate and bile samples. Biopsies of bile ducts, hepatic arteries, and liver parenchyma were collected to assess histological damage and the expression of endothelial protective genes (KLF-2, eNOS, ET-1, CD31, VWF, VEGF-A).

Results.

There were no differences in hepatobiliary function and injury after warm reperfusion between the groups, apart from a 2-fold lower concentration of alanine aminotransferase in the perfusate (P = 0.045) and a lower peak lactate dehydrogenase in bile (P = 0.04) of livers preserved by DHOPE. Endothelial cell function and injury, as assessed by perfusate nitric oxide and von Willebrand factor antigen levels, as well as endothelial protective gene expressions, were similar between the groups. The hepatic arteries of both groups showed no microscopic evidence of injury.

Conclusions.

This study did not reveal major differences in hepatobiliary or endothelial function and injury after preservation by single or dual HOPE of porcine livers donated after circulatory death.
Development and Preliminary Evaluation of a Patient-facing Educational Video About Live Kidney Donor Surgical Complications
Authors: Smith Sophia , Haseley Nicole , Keller Maria , Cadzow Renee , Feeley Thomas H. , Kayler Liise K.
Published: August 2021

Background.

Living kidney donation (LKD) improves transplant access; however, its use is compromised, in part, by individuals’ unaddressed concerns about perioperative complications.

Methods.

We developed an animated, patient-centered educational video about LKD surgical complications, with input from experts in transplantation, communication, and anthropology, 35 patients/care partners (5 LKD candidates, 5 prior LKDs, 10 kidney transplant recipients, 10 kidney transplant candidates, 5 care partners), and 1 community advocate. We then conducted an online pre-post study with 24 potential kidney donors and recipients to measure the video’s acceptability and feasibility to improve donation complication knowledge and concerns.

Results.

Knowledge of LKD surgical complications increased 23% (mean 5.7 to 7.0, P < 0.01) from pre- to post- animation viewing. Large knowledge effect size increases were observed for different levels of age, race, health literacy, and technology access. The frequency of positive responses about donation safety increased from 88% preanimation to 96% postanimation. Concerns about surgical complications remained at 17% before and after exposure. After viewing the animation, over 90% indicated positive ratings on ease of watching, understanding, and engaging.

Conclusions.

An animated educational video about LKD surgical complications was developed in collaboration with multiple stakeholders. The video was well received and promised to positively impact individuals’ knowledge and concerns.
Centre-specific bacterial pathogen typing affects infection-control decision making
Authors: Coolen Jordy P. M. , Jamin Casper , Savelkoul Paul H. M. , Rossen John W. A. , Wertheim Heiman F. L. , Matamoros Sébastien P. , van Alphen Lieke B. ,   On behalf of SIG Bioinformatics in Medical Microbiology NL Consortium*
Published: August 2021

Whole-genome sequencing is becoming the de facto standard for bacterial outbreak surveillance and infection prevention. This is accompanied by a variety of bioinformatic tools and needs bioinformatics expertise for implementation. However, little is known about the concordance of reported outbreaks when using different bioinformatic workflows. In this multi-centre proficiency testing among 13 major Dutch healthcare-affiliated centres, bacterial whole-genome outbreak analysis was assessed. Centres who participated obtained two randomized bacterial datasets of Illumina sequences, a

Klebsiella pneumoniae

and a Vancomycin-resistant Enterococcus faecium, and were asked to apply their bioinformatic workflows. Centres reported back on antimicrobial resistance, multi-locus sequence typing (MLST), and outbreak clusters. The reported clusters were analysed using a method to compare landscapes of phylogenetic trees and calculating Kendall–Colijn distances. Furthermore, fasta files were analysed by state-of-the-art single nucleotide polymorphism (SNP) analysis to mitigate the differences introduced by each centre and determine standardized SNP cut-offs. Thirteen centres participated in this study. The reported outbreak clusters revealed discrepancies between centres, even when almost identical bioinformatic workflows were used. Due to stringent filtering, some centres failed to detect extended-spectrum beta-lactamase genes and MLST loci. Applying a standardized method to determine outbreak clusters on the reported de novo assemblies, did not result in uniformity of outbreak-cluster composition among centres.
Ion-dependent structure, dynamics, and allosteric coupling in a non-selective cation channel
Authors: Lewis Adam , Kurauskas Vilius , Tonelli Marco , Henzler-Wildman Katherine
Published: August 2021

The selectivity filter (SF) determines which ions are efficiently conducted through ion channel pores. NaK is a non-selective cation channel that conducts Na+ and K+ with equal efficiency. Crystal structures of NaK suggested a rigid SF structure, but later solid-state NMR and MD simulations questioned this interpretation. Here, we use solution NMR to characterize how bound Na+ vs. K+ affects NaK SF structure and dynamics. We find that the extracellular end of the SF is flexible on the ps-ns timescale regardless of bound ion. On a slower timescale, we observe a structural change between the Na+ and K+-bound states, accompanied by increased structural heterogeneity in Na+. We also show direct evidence that the SF structure is communicated to the pore via I88 on the M2 helix. These results support a dynamic SF with multiple conformations involved in non-selective conduction. Our data also demonstrate allosteric coupling between the SF and pore-lining helices in a non-selective cation channel that is analogous to the allosteric coupling previously demonstrated for K+-selective channels, supporting the generality of this model.
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

Extracellular 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

Multiple 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

Background

Symptoms 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.

Methods

This 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.

Results

The 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.

Conclusions

AM-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 registration

German 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

Heart 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

Background

The 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 Methods

Cross-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.

Result

The 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.

Conclusion

This 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

Present 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 relevance

Laser 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

In 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

Human-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

Salinized 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

Tumours 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

Background

Multiple 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.

Results

We 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.

Conclusions

We 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

The 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 Figure

For 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

Entamoeba 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.

IMPORTANCE

Entamoeba 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.
Leaf area index estimation of even-aged oak (Quercus petraea) forests using in situ stand dendrometric parameters
Authors: Briere M. , François C. , Lebourgeois F. , Seynave I. , Vincent G. , Korboulewsky N. , Ningre F. , Perot T. , Perret S. , Calas A. , Dufrêne E.
Published: August 2021

The leaf area index (LAI) is a key characteristic of forest stand aboveground net productivity (ANP), and many methods have been developed to estimate the LAI. However, every method has flaws, e.g., methods may be destructive, require means or time and/or show intrinsic bias and estimation errors.

A relationship using basal area (G) and stand age to estimate LAI was proposed by Sonohat et al. (2004). We used literature data in addition to data form measurements campaign made in the northern half of France to build a data set with large ranges of pedoclimatic conditions, stand age and measured LAI. We validated the Sonohat et al. (2004) relationship and attempted to improve or modify it using other stand/dendrometric characteristics that could be predictors of the LAI.

The result is a series of three models using the G, age and/or quadratic mean diameter (Dg), and the models were able to estimate the LAI of an oak only even-aged forest stand with good confidence (root mean square error, RMSE < 0.75) While G is the main predictor here, age and Dg could be used conjointly or exclusively given the available data, with variable precision in the estimations.

Although these models could not, by construction, relate to the interannual variability of the LAI, they may provide the theoretical LAI of an untouched forest (no meteorological, biotic or anthropogenic perturbation) in recent years. additionally, the use of this model may be more interesting than an LAI measurement campaign, depending on the means to be invested in such a campaign.
Red queen’s race: rapid evolutionary dynamics of an expanding family of meiotic drive factors and their hpRNA suppressors
Authors: Vedanayagam Jeffrey , Lin Ching-Jung , Lai Eric C.
Published: August 2021

Meiotic drivers are a class of selfish genetic elements that are widespread across eukaryotes. As their activities are often detrimental to organismal fitness, opposing regulatory mechanisms are usually required to silence them, to ensure fair segregation during meiosis. Accordingly, the existence of such selfish elements is frequently hidden in genomes, and their molecular functions are little known. Here, we trace evolutionary steps that generated the Dox meiotic drive system in Drosophila simulans (Dsim), which distorts male:female balance (sex-ratio) by depleting male progeny. We show that Dox emerged via stepwise mobilization and acquisition of portions of multiple D. melanogaster genes, notably including from protamine, which replaces histones in haploid sperm and mediates the highly condensed state of sperm chromatin. Moreover, we reveal novel Dox homologs in Dsim and massive, recent, amplification of Dox superfamily genes specifically on X chromosomes of its closest sister species D. mauritiana (Dmau) and D. sechellia (Dsech). The emergence of Dox superfamily genes is tightly associated with 359-bp repeats (in the 1.688 family of satellite repeats) that flank de novo genomic copies. In concert, we find coordinated emergence and diversification of autosomal hairpin RNA-class siRNA loci that target subsets of Dox superfamily genes across simulans clade species. Finally, an independent set of protamine amplifications on the Y chromosome of D. melanogaster indicates that protamine genes are frequent and recurrent players in sex chromosome dynamics. Overall, we reveal fierce genetic arms races between meiotic drive factors and siRNA suppressors associated with recent speciation.
Role of autophagy in sepsis-induced skeletal muscle dysfunction, whole-body metabolism, and survival
Authors: Leduc-Gaudet Jean-Philippe , Miguez Kayla , Cefis Marina , Moamer Alaa , Chaffer Tomer Jordi , Faitg Julie , Reynaud Olivier , Broering Felipe E , Shams Anwar , Mayaki Dominique , Huck Laurent , Sandri Marco , Gouspillou Gilles , Hussain Sabah NA
Published: August 2021

Septic patients frequently develop skeletal muscle wasting and weakness, resulting in severe clinical consequences and adverse outcomes. Autophagy is a stress-induced degradative process essential to cell survival. Recent studies have demonstrated that sepsis triggers sustained induction of autophagy in skeletal muscles, although the impact of this enhanced autophagy on sepsis-induced muscle dysfunction remains unclear. Atg7 is an autophagy gene that plays a major role in autophagosome formation. Using an inducible and muscle-specific Atg7 knockout mouse model (Atg7iSkM-KO), we investigated the functional importance of skeletal muscle autophagy in sepsis. Sepsis was induced using cecal ligation and perforation (CLP) with a sham operation serving as a control. Atg7iSkM-KO mice exhibited a more severe phenotype in response to sepsis, marked by severe muscle wasting and contractile dysfunction, hypoglycemia, higher ketone levels and a decreased in survival as compared to mice with intact Atg7. Several genes that encode 26S proteasome subunits were upregulated, suggesting that activation of the ubiquitin-proteasome system is responsible for the severe muscle atrophy that was seen in these mice. Sepsis and Atg7 deletion resulted in the accumulation of mitochondrial dysfunction, although sepsis did not further worsen mitochondrial dysfunction in Atg7iSkM-KO mice. Overall, our study demonstrates that autophagy inactivation in skeletal muscles triggers significant worsening of sepsis-induced contractile and metabolic dysfunctions and negatively impacts survival. Induction of autophagy in skeletal muscles in response to sepsis thus represents a protective mechanism.
Interbacterial transfer of carbapenem resistance and large antibiotic resistance islands by natural transformation in pathogenic Acinetobacter
Authors: Godeux Anne-Sophie , Sveldhom Elin , Barreto Samuel , Potron Anaïs , Venner Samuel , Charpentier Xavier , Laaberki Maria-Halima
Published: August 2021

Acinetobacter baumannii infection poses a major health threat with recurrent treatment failure due to antibiotic resistance, notably to carbapenems. While genomic analyses of clinical strains indicate that homologous recombination plays a major role in the acquisition of antibiotic resistance genes, the underlying mechanisms of horizontal gene transfer often remain speculative. Our understanding of the acquisition of antibiotic resistance is hampered by the lack of experimental systems able to reproduce genomic observations. We here report the detection of recombination events occurring spontaneously in mixed bacterial populations and which can result in the acquisition of resistance to carbapenems. We show that natural transformation is the main driver of intra-, but also inter-strain recombination events between A. baumannii clinical isolates and pathogenic species of Acinetobacter. We observed that interbacterial natural transformation in mixed populations is more efficient at promoting the acquisition of large resistance islands (AbaR4, AbaR1) than when the same bacteria are supplied with large amounts of purified genomic DNA. Importantly, analysis of the genomes of the recombinant progeny revealed large recombination tracts (from 13 to 123 kb) similar to those observed in the genome of clinical isolates. Moreover, we highlight that transforming DNA availability is a key determinant of the rate of recombinants and results from both spontaneous release and interbacterial predatory behavior. In the light of our results, natural transformation should be considered as a leading mechanism of genome recombination and horizontal gene transfer of antibiotic resistance genes in Acinetobacter baumannii.

Importance

Acinetobacter baumannii is a multidrug resistant pathogen responsible for difficult-to-treat hospital-acquired infections. Understanding the mechanisms leading to the emergence of the multi-drug resistance in this pathogen is today crucial. Horizontal gene transfer is assumed to largely contribute to this multidrug resistance. However, in A. baumannii, the mechanisms leading to genome recombination and the horizontal transfer of resistance genes are poorly understood. We bring experimental evidence that natural transformation, a horizontal gene transfer mechanism recently highlighted in A. baumannii, allows the highly efficient interbacterial transfer of genetic elements carrying resistance to last line antibiotic carbapenems. Importantly, we demonstrated that natural transformation, occurring in mixed populations of Acinetobacter, enables the transfer of large resistance island mobilizing multiple resistance genes.
Differential use of multiple genetic sex determination systems in divergent ecomorphs of an African crater lake cichlid
Authors: Munby Hannah , Linderoth Tyler , Fischer Bettina , Du Mingliu , Vernaz Grégoire , Tyers Alexandra M. , Ngatunga Benjamin P. , Shechonge Asilatu , Denise Hubert , McCarthy Shane A. , Bista Iliana , Miska Eric A. , Santos M. Emília , Genner Martin J. , Turner George F. , Durbin Richard
Published: August 2021

African cichlid fishes not only exhibit remarkably high rates of speciation but also have some of the fastest evolving sex determination systems in vertebrates. However, little is known empirically in cichlids about the genetic mechanisms generating new sex-determining variants, what forces dictate their fate, the demographic scales at which they evolve, and whether they are related to speciation. To address these questions, we looked for sex-associated loci in full genome data from 647 individuals of Astatotilapia calliptera from Lake Masoko, a small isolated crater lake in Tanzania, which contains two distinct ecomorphs of the species. We identified three separate XY systems on recombining chromosomes. Two Y alleles derive from mutations that increase expression of the gonadal soma-derived factor gene (gsdf) on chromosome 7; the first is a tandem duplication of the entire gene observed throughout much of the Lake Malawi haplochromine cichlid radiation to which A. calliptera belongs, and the second is a 5 kb insertion directly upstream of gsdf. Both the latter variant and another 700 bp insertion on chromosome 19 responsible for the third Y allele arose from transposable element insertions. Males belonging to the Masoko deep-water benthic ecomorph are determined exclusively by the gsdf duplication, whereas all three Y alleles are used in the Masoko littoral ecomorph, in which they appear to act antagonistically among males with different amounts of benthic admixture. This antagonism in the face of ongoing admixture may be important for sustaining multifactorial sex determination in Lake Masoko. In addition to identifying the molecular basis of three coexisting sex determining alleles, these results demonstrate that genetic interactions between Y alleles and genetic background can potentially affect fitness and adaptive evolution.
Knockout of murine Lyplal1 confers sex-specific protection against diet-induced obesity
Authors: Vohnoutka Rishel B. , Kuppa Annapurna , Hegde Yash , Chen Yue , Pant Asmita , Choi Eun-Young (Karen) , McCarty Sean M. , Bagchi Devika P. , Du Xiaomeng , Chen Yanhua , Chen Vincent L. , Bielak Lawrence F. , Maguire Lillias H. , Handelman Samuel K. , Sexton Jonathan Z. , Saunders Thomas L. , Halligan Brian D. , Speliotes Elizabeth K.
Published: August 2021

Human genome-wide association studies found SNPs near LYPLAL1 that have sex-specific effects on fat distribution and metabolic traits. To determine whether altering LYPLAL1 affects obesity and metabolic disease we created and characterized a mouse knockout of Lyplal1. Here we show that CRISPR-Cas9 whole-body Lyplal1 knockout (KO) mice fed a high fat, high sucrose (HFHS) diet showed sex-specific differences in weight gain and fat accumulation. Female, not male, KO mice weighed less than WT mice, had reduced body fat percentage, white fat mass, and adipocyte diameter not accounted for by changes in metabolic rate. Female, but not male, KO mice had increased serum triglycerides, decreased aspartate, and alanine aminotransferase. Lyplal1 KO mice of both sexes have reduced liver triglycerides and steatosis. These diet-specific effects resemble the effects of SNPs near LYPLAL1 in humans, suggesting that LYPLAL1 has an evolutionary conserved sex-specific effect on adiposity. This murine model can be used to study this novel gene-by-sex-by-diet interaction to elucidate the metabolic effects of LYPLAL1 on human obesity.
Crystal structure and Hirshfeld surface analysis of (3Z)-7-methoxy-3-(2-phenylhydrazinylidene)-1-benzofuran-2(3H)-one
Authors: Atioğlu Zeliha , Akkurt Mehmet , Askerova Ulviyya F. , Mukhtarova Sevinc H. , Askerov Rizvan K. , Mlowe Sixberth
Published: August 2021

In the title compound, C15H12N2O3, pairs of molecules are linked into dimers by N—H...O hydrogen bonds, forming an R
2
2(12) ring motif, with the dimers stacked along the a axis. These dimers are connected through π–π stacking interactions between the centroids of the benzene and furan rings of their 2,3-dihydro-1-benzofuran ring systems. Furthermore, there exists a C—H...π interaction that consolidates the crystal packing. A Hirshfeld surface analysis indicates that the most important contacts are H...H (40.7%), O...H/H...O (24.7%), C...H/H...C (16.1%) and C...C (8.8%).
Online time-optimal path and trajectory planning for robotic multipoint assembly
Authors: Liu Yi , Er Meng Joo , Guo Chen
Published: August 2021

Purpose

The purpose of this paper is to propose an efficient path and trajectory planning method to solve online robotic multipoint assembly.

Design/methodology/approach

A path planning algorithm called policy memorized adaptive dynamic programming (PM-ADP) combines with a trajectory planning algorithm called adaptive elite genetic algorithm (AEGA) for online time-optimal path and trajectory planning.

Findings

Experimental results and comparative study show that the PM-ADP is more efficient and accurate than traditional algorithms in a smaller assembly task. Under the shortest assembly path, AEGA is used to plan the time-optimal trajectories of the robot and be more efficient than GA.

Practical implications

The proposed method builds a new online and efficient path planning arithmetic to cope with the uncertain and dynamic nature of the multipoint assembly path in the Cartesian space. Moreover, the optimized trajectories of the joints can make the movement of the robot continuously and efficiently.

Originality/value

The proposed method is a combination of time-optimal path planning with trajectory planning. The traveling salesman problem model of assembly path is established to transfer the assembly process into a Markov decision process (MDP). A new dynamic programming (DP) algorithm, termed PM-ADP, which combines the memorized policy and adaptivity, is developed to optimize the shortest assembly path. GA is improved, termed AEGA, which is used for online time-optimal trajectory planning in joints space.
The post-SOX comparative dynamics of public accounting firm efficiency
Authors: Clark Ephraim , Qiao Zhuo
Published: August 2021

Purpose

This paper aims to analyze the differences in the efficiency of public accounting firms across both firms and countries in the post-Sarbanes-Oxley world. It also investigates the issues surrounding the dynamics of their efficiency gaps.

Design/methodology/approach

This study uses four-stage data envelopment analysis to estimate the efficiency of public accounting firms in the USA, the UK and Canada over the period 2008–2015. The ß- and σ- convergence tests are applied to analyze the dynamics of the efficiency gaps across firms and countries.

Findings

The results show that market competition in the accounting sector increases efficiency. Gross domestic product growth also increases it while inflation decreases it. The analytical results indicate that the lagging public accounting firms are catching up to the leading public accounting firms within the same country, within the Big 4 group and within the non-Big 4 group. They also show that the non-Big 4 groups are catching up to the Big 4 group and that the countries with less efficient accounting firms are catching up to the country with the more efficient accounting firms.

Originality/value

This study accounts explicitly for the effect of business environmental factors on public accounting firm efficiency. Furthermore, the research also adds to the literature by investigating the comparative dynamics of the efficiency gaps of public accounting firms.