bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fever-like temperature impacts onStaphylococcus aureusandPseudomonas aeruginosainteraction, physiology, and virulence bothin vitroandin vivo
Authors: Solar Venero EC , Galeano MB , Luqman A , Ricardi MM , Serral F , Fernandez Do Porto D , Robaldi SA , Ashari BAZ , Munif TH , Egoburo DE , Nemirovsky S , Escalante J , Nishimura B , Ramirez MS , Götz F , Tribelli PM 
Published: March 2023

AbstractBackgroundStaphylococcus aureusandPseudomonas aeruginosacause a wide variety of bacterial infections and coinfections, showing a complex interaction that involves the production of different metabolites and metabolic changes. Temperature is a key factor for bacterial survival and virulence and within the host, bacteria could be exposed to an increment in temperature during fever development. We analyzed the previously unexplored effect of fever-like temperatures (39°C) onS. aureusUSA300 andP. aeruginosaPAO1 microaerobic mono- and co-cultures compared with 37°C, by using RNAseq and physiological assays includingin-vivoexperiments.ResultsIn general terms both temperature and co-culturing had a strong impact on both PA and SA with the exception of the temperature response of monocultured PA. We studied metabolic and virulence changes on both species. Altered metabolic features at 39°C included arginine biosynthesis and the periplasmic glucose oxidation inS. aureusandP. aeruginosamonocultures respectively. When PA co-cultures were exposed at 39°C they upregulated ethanol oxidation related genes along with an increment in organic acid accumulation. Regarding virulence factors, monocultured SA showed an increase in the mRNA expression of theagroperon andhld, pmsαandpmsβgenes at 39°C. Supported by mRNA data, we performed physiological experiments and detected and increment in hemolysis, staphylxantin production and a decrease in biofilm formation at 39°C. On the side of PA monocultures, we observed increase in extracellular lipase and protease and biofilm formation at 39°C along with a decrease in motility in correlation with changes observed at mRNA abundance. Additionally, we assessed host-pathogen interaction bothin-vitroandin-vivo.S. aureusmonocultured at 39°C showed a decrease in cellular invasion and an increase in IL-8 -but not in IL-6- production by A549 cell line. PA also decreased its cellular invasion when monocultured at 39°C and did not induce any change in IL-8 or IL-6 production. PA strongly increased cellular invasion when co-cultured at 37°C and 39°C. Finally, we observed increased lethality in mice intranasally inoculated withS. aureusmonocultures pre-incubated at 39°C and even higher levels when inoculated with co-cultures. The bacterial burden forP. aeruginosawas higher in liver when the mice were infected with co-cultures previously incubated at 39°C comparing with 37°C.ConclusionOur results highlight a relevant change in the virulence of bacterial opportunistic pathogens exposed to fever-like temperatures in presence of competitors, opening new questions related to bacteria-bacteria and host-pathogen interactions and coevolution.
An epigenetic molluscicide
Authors: Luviano Nelia , Halby Ludovic , Jallet Corinne , Arimondo Paola B. , Cosseau Celine , Grunau Christoph 
Published: March 2023

AbstractBiomphalaria glabratais a fresh-water mollusk that serves as obligatory intermediate host toSchistosoma mansoni, agent of the neglected tropical disease schistosomiasis that affects roughly 250 Mio people. One of the ways to control the pathogenic agent is to interrupt the life cycle by eliminating the intermediate snail host though foal treatment of water bodies with molluscicides. Currently recommended molluscicides were developed in the 1950ths and lack sufficient specificity, e.g., they are toxic to fish. To provide new lead compounds for the development of a new type of molluscicides we used a rational approach based on the hypotheses that interfering with an important epigenetic mark, DNA methylation, would impede development of the snail host. We present here the compound 29, analogues-based compound that mimic substrates of DNA methyltransferases. We show that compound 29 has (i) low cytotoxicity for human cells, (ii) it inhibits DNA methylation, and (iii) it decreases fecundity inB.glabrata. It is therefore conceivable to produce compounds that act as specific epigenetic molluscicides.
Endocytic myosin-1 is a force-insensitive, power-generating motor
Authors: Pedersen Ross TA , Snoberger Aaron , Pyrpassopoulos Serapion , Safer Daniel , Drubin David G , Ostap E Michael 
Published: March 2023

AbstractMyosins are required for clathrin-mediated endocytosis, but their precise molecular roles in this process are not known. This is, in part, because the biophysical properties of the relevant motors have not been investigated. Myosins have diverse mechanochemical activities, ranging from powerful contractility against mechanical loads to force-sensitive anchoring. To better understand the essential molecular contribution of myosin to endocytosis, we studied the in vitro force-dependent kinetics of theSaccharomyces cerevisiaeendocytic type I myosin called Myo5, a motor whose role in clathrin-mediated endocytosis has been meticulously studied in vivo. We report that Myo5 is a low-duty-ratio motor that is activated ∼10-fold by phosphorylation, and that its working stroke and actin-detachment kinetics are relatively force-insensitive. Strikingly, the in vitro mechanochemistry of Myo5 is more like that of cardiac myosin than like that of slow anchoring myosin-1s found on endosomal membranes. We therefore propose that Myo5 generates power to augment actin assembly-based forces during endocytosis in cells.SummaryPedersen, Snoberger et al. measure the force-sensitivity of the yeast endocytic the myosin-1 called Myo5 and find that it is more likely to generate power than to serve as a force-sensitive anchor in cells. Implications for Myo5’s role in clathrin-mediated endocytosis are discussed.
Effectiveness of using reward strategies combined with transcranial direct current stimulation (RstDCS) on motivation in chronic stroke patients with upper limb disorders: study protocol for a randomized controlled trial
Authors: Zhou Ping , Li Wenxi , Zhao Jingwang , Chen Siyun , Chen Yufeng , Shen Xia , Xu Dongsheng 
Published: March 2023

AbstractIntroductionStroke survivors tend to have low motivation for rehabilitation, which prevent them from completing the rehabilitation training task effectively and participating in daily activities. Reward strategies can stimulate patients’ motivation for rehabilitation, but the duration of their effect is unknown. tDCS is a technique capable of promoting plastic changes and functional reorganization of cortical functional areas. When it acts on dlPFC, it can improve the functional connectivity of brain areas associated with goal-directed behavior. Reward strategies combined with tDCS (RstDCS) have been shown to make normal individuals work harder at performing tasks. However, there are no studies on whether this combined strategy improves motivation in stroke patients and whether it has a long-lasting effect on motivation maintenance.Methods and analysis87 stroke survivors who have low motivation and upper extremity dysfunction will be randomized to receive conventional, Rs, or RstDCS treatment. Patients in each group will undertake 15 sessions of tDCS real or sham stimulation of the left dlPFC for 3 weeks in conjunction with conventional rehabilitation or reward strategy training. Following this, the RS treatment group and RstDCS treatment group will be given a 3-week outpatient self-monitoring training program, while the conventional group will be given home rehabilitation instruction prior to discharge.Rehabilitation motivation is the primary outcome measure and will be assessed using RMS. RMS,FMA, FIM and ICF activity and social engagement scale will be compared at baseline, 3 weeks, 6 weeks, and 3 months after enrollment.Ethics and disseminationThe study has been approved by the Ethics Committee of Yueyang Hospital of Integrated Chinese and Western Medicine Affiliated to SHUTCM (2021-122). All participating patients will provide written informed consent. The results will be disseminated through (open access) peer-reviewed publications, networks of scientists, professionals, and the public.Trial registration number:ChiCTR2300069068
Cardiovascular events and venous thromboembolism after primary malignant and non-malignant brain tumour diagnosis: a population matched cohort study in Wales (United Kingdom)
Authors: Poon Michael TC , Brennan Paul M , Jin Kai , Sudlow Cathie LM , Figueroa Jonine D 
Published: March 2023

AbstractBackgroundElevated standardised mortality ratio of cardiovascular diseases (CVD) in patients with brain tumours may result from differences in the distribution of risk factors. We compared the risk of CVD among patients with a primary malignant or non-malignant brain tumour to a matched general population cohort, accounting for other co-morbidities.MethodsUsing data from the Secured Anonymised Information Linkage (SAIL) Databank in Wales (United Kingdom), we identified all adults aged ≥18 years in the primary care database with first diagnosis of malignant and non-malignant brain tumour identified in the cancer registry in 2000-2014, and a matched cohort (case-to-control ratio 1:5) by age, sex and primary care provider from the general population without any tumour diagnosis. Outcomes included fatal and non-fatal major vascular events (stroke, ischaemic heart disease, aortic and peripheral vascular diseases) and venous thromboembolism (VTE). We used multivariable cox models adjusted for clinical risk factors to compare risks, stratified by tumour behaviour and follow-up period.ResultsThere were 2,869 and 3,931 people diagnosed with malignant and non-malignant brain tumours, respectively, between 2000 and 2014 in Wales. They were matched to 33,785 controls. Within the first year of tumour diagnosis, malignant tumour was associated with a higher risk of VTE (hazard ratio [HR] 21.58, 95% confidence interval 16.12-28.88) and stroke (HR 3.32, 2.44-4.53). Risks of VTE (HR 2.20, 1.52-3.18) and stroke (HR 1.45, 1.00-2.10) remained to be higher than controls for those surviving one year. Patients with non-malignant tumours had higher risks of VTE (HR 3.72, 2.73-5.06), stroke (HR 4.06, 3.35-4.93) and aortic and peripheral arterial disease (HR 2.09, 1.26-3.48) within the first year of diagnosis compared with their controls.ConclusionsThe elevated CVD and VTE risks suggested risk reduction may be a strategy to improve life quality and survival in people with a brain tumour.
Whole blood DNA methylation changes are associated with anti-TNF drug concentration in patients with Crohn’s disease
Authors: Lin Simeng , Hannon Eilis , Reppell Mark , Waring Jeffrey F. , Smaoui Nizar , Pivorunas Valerie , Guay Heath , Chanchlani Neil , Bewshea Claire , Bai Benjamin Y H , Kennedy Nicholas A , Goodhand James R , Mill Jonathan , Ahmad Tariq ,   PANTS Consortium
Published: March 2023

AbstractBackground and AimsAnti-TNF treatment failure in patients with inflammatory bowel disease (IBD) is common and frequently related to low drug concentrations.In order to identify patients who may benefit from dose optimisation at the outset of anti-TNF therapy, we sought to define epigenetic biomarkers in whole blood at baseline associated with anti-TNF drug concentrations at week 14.MethodsDNA methylation from 1,104 whole blood samples from the Personalised Anti-TNF Therapy in Crohn’s disease (PANTS) study were assessed using the Illumina EPIC Beadchip at baseline, weeks 14, 30 and 54. We compared DNA methylation profiles in anti-TNF-treated patients who experienced primary non-response at week 14 and were not in remission at week 30 or 54 (infliximab n = 99, adalimumab n = 94) with patients who responded at week 14 and were in remission at week 30 or 54 (infliximab n = 99, adalimumab n = 93).ResultsOverall, between baseline and week 14, we observed 4,999 differentially methylated probes (DMPs) annotated to 2376 genes following anti-TNF treatment. Pathway analysis identified 108 significant gene ontology terms enriched in biological processes related to immune system processes and responses.Epigenome-wide association (EWAS) analysis identified 323 DMPs annotated to 210 genes at baseline associated with higher anti-TNF drug concentrations at week 14. Of these, 125 DMPs demonstrated shared associations with other common traits (proportion of shared CpGs compared to DMPs) including body mass index (23.2%), followed by CRP (11.5%), smoking (7.4%), alcohol consumption per day (7.1%) and IBD type (6.8%). EWAS of primary non-response to anti-TNF identified 20 DMPs that were associated with both anti-TNF drug concentration and primary non-response to anti-TNF with a strong correlation of the coefficients (Spearman’s rho = −0.94, p < 0.001).ConclusionBaseline DNA methylation profiles may be used as a predictor for anti-TNF drug concentration at week 14 to identify patients who may benefit from dose optimisation at the outset of anti-TNF therapy.
Time trends and modifiable factors of contact tracing coverage in Geneva, Switzerland, June 2020 to February 2022
Authors: Mongin Denis , Bürgisser Nils ,   the Covid-SMC Study Group, Courvoisier Delphine Sophie 
Published: March 2023

AbstractBackgroundContact tracing has been one of the central non-pharmaceutical interventions implemented worldwide to try to control the spread of Sars-CoV-2, but its effectiveness strongly depends on its ability to detect contacts.MethodsWe analysed 166’892 concomitant infections occurring at the same address from June 2020 until February 2022 using an extensive operational database of SARS-CoV-2 tests in Geneva and used permutations statistics to compare the total number of secondary infections occurring at the address with those reported through contact tracing.ResultsManual contact tracing captured on average 41% of the secondary infections, with variation in time from 23% during epidemic peaks to 60% during low epidemic activity. People living in wealthy neighbourhoods were less likely to report contacts (adjusted odds ratio (aOR): 1.6). People living in buildings, compared to people living in single house, were also less likely to report contacts than those living in houses, with an aOR of 1.1 to 3.1 depending on the variant, the size of the building and the presence of shops. This under-reporting of contacts in buildings decreased during periods of mandatory face masking and restriction of private gathering.ConclusionsContact tracing alone does not detect enough secondary infections to efficiently reduce the propagation of Sars-CoV-2. Public messages and outreach campaigns targeting specific populations, such as those in affluent areas, could enhance coverage. Additionally, measures like wearing face masks, improving ventilation, and implementing gathering restrictions should also be considered to reduce the number of infections occurring during interactions that may not be perceived as high risk.
Structure and Function of the Dot/Icm T4SS
Authors: Dutka Przemysław , Liu Yuxi , Maggi Stefano , Ghosal Debnath , Wang Jue , Carter Stephen D. , Zhao Wei , Vijayrajratnam Sukhithasri , Vogel Joseph P. , Jensen Grant J. 
Published: March 2023

AbstractTheLegionella pneumophilaDot/Icm type IV secretion system (T4SS) delivers effector proteins into host cells during infection. Despite its significance as a potential drug target, our current understanding of its atomic structure is limited to isolated subcomplexes. In this study, we used subtomogram averaging and integrative modeling to construct a nearly-complete model of the Dot/Icm T4SS accounting for seventeen protein components. We locate and provide insights into the structure and function of six new components including DotI, DotJ, DotU, IcmF, IcmT, and IcmX. We find that the cytosolic N-terminal domain of IcmF, a key protein forming a central hollow cylinder, interacts with DotU, providing insight into previously uncharacterized density. Furthermore, our model, in combination with analyses of compositional heterogeneity, explains how the cytoplasmic ATPase DotO is connected to the periplasmic complex via interactions with membrane-bound DotI/DotJ proteins. Coupled within situinfection data, our model offers new insights into the T4SS-mediated secretion mechanism.
Temporal genome-wide fitness analysis ofMycobacterium marinumduring infection reveals genetic requirement for virulence and survival in amoebae and microglial cells
Authors: Lefrançois Louise H. , Nitschke Jahn , Panis Gaël , Prados Julien , Butler Rachel E. , Mendum Tom A. , Hanna Nabil , Stewart Graham R. , Soldati Thierry 
Published: March 2023

ABSTRACTTuberculosis remains the most pervasive infectious disease and the recent emergence of multiple or even fully drug-resistant strains increases the risk and emphasizes the need for more efficient and better drug treatments. A key feature of mycobacteria pathogenesis is the metabolic switch during infection and expression of virulence genes is often adapted to specific infection conditions. This study aims to identify genes that are involved in the establishment and maintenance of the infection. To answer these questions, we have applied Transposon Sequencing (Tn-Seq) inM. marinum, an unbiased genome-wide strategy that combines saturation insertional mutagenesis and high throughput sequencing. This approach allowed us to precisely identify the localization and relative abundance of insertions in pools of Tn mutants. The essentiality and fitness cost, in terms of growth advantage and disadvantage of over 105mutants were quantitatively compared betweenin vitroand different stages of infection in two evolutionary distinct hosts,D. discoideumand BV2 microglial cells. We found that 57% of TA sites in theM. marinumgenome were disrupted and that 568 genes (10.2%) are essential forM. marinum, which is comparable to previous Tn-Seq studies onM. tuberculosis. The major pathways involved in the survival ofM. marinumduring infection ofD. discoideumwere related to vitamin metabolism, theesx-1operon, as well as the mce1 operon.
Experimental validation of the mechanism of stomatal development diversification
Authors: Doll Yuki , Koga Hiroyuki , Tsukaya Hirokazu 
Published: March 2023

AbstractStomata are the structures responsible for gas exchange in plants. The established framework for stomatal development is based on the model plant Arabidopsis, but diverse patterns of stomatal development have been observed in other plant lineages and species. The molecular mechanisms behind these diversified patterns are still poorly understood. We recently proposed a model for the molecular mechanisms of the diversification of stomatal development based on the genusCallitriche(Plantaginaceae), according to which a temporal shift in the expression of key stomatal transcription factors SPEECHLESS and MUTE leads to changes in the behavior of meristemoids (stomatal precursor cells). In the present study, we have tried to validate this model through genetic manipulation experiments on Arabidopsis. By altering the timing of MUTE expression, we successfully generated Arabidopsis plants with early differentiation or prolonged divisions of meristemoids, as predicted by the model. The epidermal morphology of the generated lines resembled that of species with prolonged or no meristemoid divisions. Thus, the evolutionary process was reproduced via shifting MUTE expression. We also observed unexpected phenotypes, which indicated the participation of additional factors in the evolution of the patterns observed in nature. This study provides novel experimental insights into the diversification of meristemoid behaviors.HighlightGenetic manipulation in Arabidopsis uncovered how changes in temporal gene expression patterns lead to the diversification of stomatal patterns, providing new experimental insights into the evolution of stomatal development.
Interspecies interactions determine growth dynamics of biopolymer degrading populations in microbial communities
Authors: D’Souza Glen , Schwartzman Julia , Keegstra Johannes , Schreier Jeremy E , Daniels Michael , Cordero Otto , Stocker Roman , Ackermann Martin 
Published: March 2023

AbstractMicrobial communities perform essential ecosystem functions such as the remineralization of organic carbon that exists as biopolymers. The first step in mineralization is performed by biopolymer degraders, which harbor enzymes that can break down polymers into constituent oligo- or monomeric forms. The released nutrients not only allow degraders to grow, but also promote growth of cells that either consume the breakdown products, i.e., exploiters, or consume metabolites released by the degraders, i.e., scavengers. It is currently not clear how such remineralizing communities assemble at the microscale – how interactions between the different guilds influence their growth and spatial distribution, and hence the development and dynamics of the community. Here we address this knowledge gap by studying marine microbial communities that grow on the abundant marine biopolymer alginate. We used batch growth assays and microfluidics coupled to time-lapse microscopy to quantitatively investigate growth and spatial distribution of single cells. We found that the presence of exploiters or scavengers alters the spatial distribution of degrader cells. In general, exploiters and scavengers – which we collectively refer to as consumer cells – slowed down the growth of degrader cells. In addition, coexistence with consumers altered the production of the extracellular enzymes that breakdown polymers by degrader cells. Our findings reveal that ecological interactions by non-degrading community members have a profound impact on the functions of microbial communities that remineralize carbon biopolymers in nature.ImportanceBiopolymers are the most abundant source of carbon on the planet and their breakdown by microbial degraders releases metabolic products that allow cross-feeding cells to grow and fuel the assembly of microbial communities. While it is known that the growth of degraders can facilitate growth of downstream cross-feeders in microbial communities, it has remained generally unclear if and how cross-feeders influence growth of degraders. Bridging this knowledge gap is important because degraders primarily drive the remineralization of carbon, a central process in the carbon cycle. We found that the presence cross-feeders can influence the growth of degraders by altering their spatial distribution as well as extracellular breakdown enzyme activity. Our study sheds light on the role of microbial interactions in shaping the rate of carbon remineralization in nature.
Multicellular PD Control in Microbial Consortia
Authors: Martinelli Vittoria , Salzano Davide , Fiore Davide , di Bernardo Mario 
Published: March 2023

AbstractWe propose a multicellular implementation of a biomolecular PD feedback controller to regulate gene expression in a microbial consortium. The implementation involves distributing the proportional and derivative control actions between two different cellular populations that can communicate with each other and regulate the output of a third target cellular population. We derive analytical conditions on biological parameters and control gains to adjust the system’s static and dynamical properties. We then validate the strategy’s performance and robustness through extensivein silicoexperiments.