bluuebunny/crossref_metadata_2025_split huggingface dataset:
The fate of sulfamethoxazole and trimethoprim in a micro-aerated anaerobic membrane bioreactor: implications for antibiotic resistance spreading
Authors: Piaggio Antonella L. , Mittapalli Srilekha , Calderón-Franco David , Weissbrodt David G. , van Lier Jules B. , de Kreuk Merle K. , Lindeboom Ralph E.F. 
Published: July 2023

AbstractInterest in reusing treated wastewater drives efforts to eliminate antibiotics from water sources to prevent antibiotic resistance. Micro-aerated anaerobic membrane bioreactors (MA-AnMBR) promote wastewater reuse with high organic matter conversion to biogas, under a small footprint. However, the fates of antibiotics, antibiotic-resistant bacteria (ARB), and their antibiotic-resistance genes (ARGs) are not known in these systems. We studied the effects, conversions, and resistance induction, following the addition of 150 μg·L-1of two antibiotics, sulfamethoxazole (SMX) and trimethoprim (TMP), in a laboratory-scale MA-AnMBR. TMP and SMX were removed at 97 and 86%, indicating that micro-aeration did not hamper the removal of the antibiotics. These antibiotics only affected the pH and biogas composition of the process, with a significant change in pH from 7.8 to 7.5, and a decrease in biogas CH4content from 84 to 78%. TMP was rapidly adsorbed onto the sludge and subsequently degraded during the long retention of the solids of 27 days. SMX adsorption was minimal, but the applied hydraulic retention time of 2.6 days was sufficiently long to biodegrade SMX. The levels of three ARGs (sul1andsul2for SMX,dfrA1) and one mobile genetic element biomarker (intI1) were analysed by qPCR, in combination with ARB tracked by plating. Additions of the antibiotics increased the relative abundances of all ARGs andintI1in the MA-AnMBR sludge, with thesul2gene folding 15 times after 310 days of operation. The MA-AnMBR was able to reduce the concentration of ARB in the permeate by 3 log.HighlightsAdditions of SMX and TMP had a negligible effect on the MA-AnMBR performance.The laboratory-scale MA-AnMBR removed 86% of SMX and 97% of TMP.A 3 log removal of ARB was achieved between sludge and UF permeate.Relative abundances of ARGs were similar in sludge and permeate.TMP and SMX resistance is better assessed by the heterotrophic plate count of ARB.
The night-time sleep and autonomic activity of male and female professional road cyclists competing in the Tour de France and Tour de France Femmes
Authors: Sargent Charli , Jasinski Summer , Capodilupo Emily R. , Powers Jeremy , Miller Dean J. , Roach Gregory D. 
Published: July 2023

AbstractObjectiveThe objective of this study was to examine the capacity of male and female professional cyclists to recover between daily race stages while competing in the 109thedition of the Tour de France (2022) and the 1stedition of the Tour de France Femmes (2022), respectively.MethodsThe 17 participating cyclists were 8 males from a single team (aged 28.0 ± 2.5 years [mean ± 95% confidence interval]) and 9 females from two separate teams (aged 26.7 ± 3.1 years). Cyclists wore a fitness tracker (WHOOP 4.0) to capture recovery metrics primarily related to night-time sleep and autonomic activity. Data were collected for the entirety of the events and for 7 days of baseline before the events. The primary analyses tested for a main effect of ‘stage type’ – i.e., rest, flat, hilly, mountain or time trial for males and flat, hilly or mountain for females – on the various recovery metrics.ResultsDuring baseline, total sleep time at night was 7.2 ± 0.3 h for male cyclists and 7.7 ± 0.3 h for female cyclists, sleep efficiency (i.e., total sleep time as a percentage of time in bed) was 87.0 ± 4.4 % for males and 88.8 ± 2.6 % for females, resting heart rate was 41.8 ± 4.5 beats·min-1for males and 45.8 ± 4.9 beats·min-1for females, and heart rate variability during sleep was 108.7 ± 17.0 ms for males and 119.8 ± 26.4 ms for females. During their respective events, total sleep time at night was 7.2 ± 0.1 h for males and 7.5 ± 0.3 h for females, sleep efficiency was 86.4 ± 1.2 % for males and 89.6 ± 1.2 % for females, resting heart rate was 44.5 ± 1.2 beats·min-1for males and 50.2 ± 2.0 beats·min-1for females, and heart rate variability during sleep was 99.1 ± 4.2 ms for males and 114.3 ± 11.2 ms for females. For male cyclists, there was a main effect of ‘stage type’ on recovery, such that heart rate variability during sleep was lowest after mountain stages. For female cyclists, there was also a main effect of ‘stage type’ on recovery, such that the percentage of light sleep in a sleep period (i.e., lower-quality sleep) was highest after mountain stages.ConclusionsSome aspects of recovery were compromised in cyclists after the most demanding days of racing, i.e., mountain stages. Overall however, the cyclists obtained a reasonable amount of good-quality sleep while competing in these highly demanding endurance events. This study demonstrates that it is now feasible to assess recovery metrics in professional athletes during multiple-day endurance events using validated fitness trackers.
Strengthening Community Roots: Anchoring Newcomers in Wellness and Sustainability (SCORE!): A protocol for the co-design and evaluation of a healthy active living program among a newcomer community in Canada
Authors: Wahi Gita , Kandasamy Sujane , Bangdiwala Shrikant , Baumann Andrea , Arsenio Mary Crea- , Desai Dipika , Georgiades Kathy , Jackson-Best Fatimah , Kwan Matthew , Montague Patricia , Newbold Bruce , Sherifali Diana , Sim Amanda , de Souza Russell J. , Anand Sonia S. 
Published: July 2023

ABSTRACTBACKGROUNDThe burden of childhood obesity and cardiometabolic risk factors affecting newcomer Canadians living in lower socioeconomic circumstances is a concerning public health issue. This paper describes Strengthening Community Roots: Anchoring Newcomers in Wellness and Sustainability (SCORE!), an academic-community research partnership to co-design interventions that nurture and optimize healthy activity living (HAL) among a community of children and families new to Canada in Hamilton, Ontario, Canada.METHODS/DESIGNOur overarching program is informed by a socio-ecological model, and will co-create HAL interventions for children and families new to Canada rooted in outdoor, nature-based physical activity. We will proceed in three phases: Phase 1) synthesis of existing evidence regarding nature based HAL interventions among children and families; Phase 2) program development through four data collection activities including: i) community engagement activities to build trustful relationships and understand barriers and facilitators, including establishing a community advisory and action board, qualitative studies including a photovoice study, and co-design workshops to develop programs; ii) characterizing the demographics of the community through a household survey; iii) characterizing the built environment and HAL programs/services available in the community by developing an accessible real-time systems map; and iv) reviewing municipal policies relevant to HAL and sustainability; leading to Phase 3) implementation and evaluation of the feasibility of co-designed HAL programs.CONCLUSIONThe etiology of childhood obesity and related chronic diseases is complex and multifactorial, as are intervention strategies. The SCORE! program of research brings together partners including community members, service providers, academic researchers, and organizational leaders to build a multi-component intervention that promotes the health and wellness of newcomer children and families.
Mon1a and FCHO2 are required for maintenance of Golgi architecture
Authors: Bagley Dustin C. , Morham Scott G. , Kaplan Jerry , Ward Diane M. 
Published: July 2023

AbstractMon1a has been shown to function in the endolysosomal pathway functioning in the Mon1-Ccz1 complex and it also acts in the secretory pathway where it interacts with dynein and affects ER to Golgi traffic. Here we show that Mon1a is also required for maintenance of the Golgi apparatus. We identified the F-BAR protein FCHO2 as a Mon1a-interacting protein by both yeast two-hybrid analysis and co-immunoprecipitation. siRNA-dependent reductions in Mon1a or FCHO2 resulted in Golgi fragmentation. Membrane trafficking through the secretory apparatus in FCHO2-depleted cells was unaltered, however, reduction of FCHO2 affected the uniform distribution of Golgi enzymes necessary for carbohydrate modification. Fluorescence recovery after photobleaching analysis showed that the Golgi ministacks in Mon1a- or FCHO2-silenced cells did not exchange resident membrane proteins. The effect of FCHO2 silencing on Golgi structure was partially cell cycle-dependent and required mitosis-dependent Golgi fragmentation, whereas the effect of Mon1a-silencing on Golgi disruption was not cell cycle-dependent. mCherry-FCHO2 transiently colocalized on Golgi structures independent of Mon1a. These findings suggest that Mon1a has functions throughout the secretory pathway including interacting with dynein at the ER-Golgi interface in vesicle formation and then interacting with FCHO2 at the Golgi to generate lateral links between ministacks, thus creating Golgi ribbons.
Coupled Environmental and Demographic Fluctuations Shape the Evolution of Cooperative Antimicrobial Resistance
Authors: Hernández-Navarro Lluís , Asker Matthew , Rucklidge Alastair M. , Mobilia Mauro 
Published: July 2023

AbstractThere is a pressing need to better understand how microbial populations respond to antimicrobial drugs, and to find mechanisms to possibly eradicate antimicrobial-resistant cells. The inactivation of antimicrobials by resistant microbes can often be viewed as a cooperative behavior leading to the coexistence of resistant and sensitive cells in large populations and static environments. This picture is however greatly altered by the fluctuations arising in volatile environments, in which microbial communities commonly evolve. Here, we study the eco-evolutionary dynamics of a population consisting of an antimicrobial resistant strain and microbes sensitive to antimicrobial drugs in a time-fluctuating environment, modeled by a carrying capacity randomly switching between states of abundance and scarcity. We assume that antimicrobial resistance is a shared public good when the number of resistant cells exceeds a certain threshold. Eco-evolutionary dynamics is thus characterized by demographic noise (birth and death events) coupled to environmental fluctuations which can cause population bottlenecks. By combining analytical and computational means, we determine the environmental conditions for the long-lived coexistence and fixation of both strains, and characterize afluctuation-drivenantimicrobial resistance eradication mechanism, where resistant microbes experience bottlenecks leading to extinction. We also discuss the possible applications of our findings to laboratory-controlled experiments.
A stress sensor IRE1α is required for bacterial exotoxin-induced inflammasome activation in tissue-resident macrophages
Authors: Sasaki Izumi , Fukuda-Ohta Yuri , Nakai Chihiro , Wakaki-Nishiyama Naoko , Okamoto Chizuyo , Orimo Takashi , Okuzaki Daisuke , Morita Shuhei , Kaji Shiori , Furuta Yuki , Hemmi Hiroaki , Kato Takashi , Yamamoto Asumi , Tanaka Takashi , Hoshino Katsuaki , Fukuda Shinji , Miyake Kensuke , Kuroda Etsushi , Ishii Ken J. , Iwawaki Takao , Furukawa Koichi , Kaisho Tsuneyasu 
Published: July 2023

AbstractCholera toxin (CT), a bacterial exotoxin composed of one A subunit (CTA) and five B subunits (CTB), functions as an immune adjuvant. CTB can induce production of interleukin-1β (IL-1β), a proinflammatory cytokine, in synergy with a lipopolysaccharide (LPS), from resident peritoneal macrophages (RPMs) through the pyrin and NLRP3 inflammasomes. However, how CTB or CT activates these inflammasomes in the macrophages has been unclear. Here, we clarified the roles of IRE1α, an endoplasmic reticulum (ER) stress sensor, in CT-induced IL-1β production from RPMs. In RPMs, CTB is incorporated into ER and induced ER stress responses, depending on GM1, a cell membrane ganglioside. IRE1α-deficient RPMs showed a significant impairment of CT- or CTB-induced IL-1β production, indicating that IRE1α was required for CT- or CTB-induced IL-1β production from RPMs. This study first demonstrates the critical roles of IRE1α in activation of both NLRP3 and pyrin inflammasomes in tissue-resident macrophages.One sentence summaryIRE1α is required for NLRP3 and pyrin-mediated IL-1β production
Breaking Down Cell-Free DNA Fragmentation: A Markov Model Approach
Authors: Tsui Terence H.L. , Xie Phil F. , Chulián Salvador , Pérez-García Víctor M. 
Published: July 2023

AbstractCell-free DNA (cfDNA) is released into the bloodstream from cells in various physiological and pathological conditions. The use of cfDNA as a non-invasive biomarker has attracted attention, but the dynamics of cfDNA fragmentation in the bloodstream are not well understood and have not been previously studied computationally.To address this issue, we present a Markovian model called FRIME (Fragmentation, Immigration, and Exit) that captures three leading mechanisms governing cfDNA fragmentation in the bloodstream. The FRIME model enables the simulation of cfDNA fragment profiles by sampling from the stationary distribution of FRIME processes. By varying the parameters of our model, we generate fragment profiles similar to those observed in liquid biopsies and provide insight into the underlying biological mechanisms driving the fragmentation dynamics.To validate our model, we compare simulated FRIME profiles with mitochondrial and genomic cfDNA fragment profiles. Our simulation results are consistent with experimental and clinical observations and highlight potential physicochemical differences between mitochondrial and genomic cfDNA.The FRIME simulation framework provides an initial step towards an improved computational understanding of DNA fragmentation dynamics in the bloodstream and may aid in the analysis of liquid biopsy data.Author summaryCell-free DNA (cfDNA) released into the bloodstream from cells in different conditions is the basis for liquid biopsies, thus being non-invasive biomarkers of potential interest. However, the dynamics of cfDNA fragmentation in the bloodstream remain poorly understood and are yet to be studied computationally. To address this issue, we developed a Markovian model which captures the three leading mechanisms governing cfDNA fragmentation in the bloodstream: FRagmentation, IMmigration, and Exit (FRIME). The FRIME model enables the simulation of cfDNA fragment profiles by sampling from the stationary distribution of FRIME processes. Simulation results are compared with mitochondrial and genomic cfDNA fragment profiles, which show consistency with experimental and clinical observations. The FRIME simulation framework is a significant step towards understanding DNA fragmentation dynamics in the bloodstream, uncovering potential physicochemical differences between mitochondrial and genomic cfDNA, and aiding the analysis of liquid biopsy data.
Induction of plant disease resistance by mixed oligosaccharide elicitors prepared from plant cell wall and crustacean shells
Authors: Pring Sreynich , Kato Hiroaki , Imano Sayaka , Camagna Maurizio , Tanaka Aiko , Kimoto Hisashi , Chen Pengru , Shrotri Abhijit , Kobayashi Hirokazu , Fukuoka Atsushi , Saito Makoto , Suzuki Takamasa , Terauchi Ryohei , Sato Ikuo , Chiba Sotaro , Takemoto Daigo 
Published: July 2023

ABSTRACTBasal plant immune responses are activated by the recognition of the conserved pathogen-associated molecular patterns (PAMPs), or breakdown molecules released from plants after damage by pathogen infection, so-called danger-associated molecular patterns (DAMPs). While chitin-oligosaccharide (CHOS), a primary component of the fungal cell wall, is most known as PAMP, plant cell wall-derived oligosaccharides, cello-oligosaccharides (COS) from cellulose and xylo-oligosaccharide (XOS) from hemicellulose, are representative DAMPs, which activate signaling steps similar to PAMP-induced immunity to elicit defenses and provide protection against pathogens. In this study, elicitor activities of COS prepared from cotton linters, XOS prepared from corn cobs as well as chitin-oligosaccharide (CHOS) from crustacean shells were comparatively investigated. In Arabidopsis, treatment of COS, XOS or CHOS triggered typical defense responses such as reactive oxygen species (ROS) production, activation of MAP kinases phosphorylation, callose depositions, and activation of the promoter for defense-related transcription factorWRKY33. When COS, XOS and CHOS were used at concentrations with similar activity in inducing ROS production and callose depositions, CHOS was particularly highly potent in activating the MAPK kinases andWRKY33promoters. Among the COS and XOS with different degrees of polymerization (DP), cellotriose (DP3) and xylotetraose (DP4) showed the highest activity for the activation ofWRKY33promoter. Simultaneous treatment of COS, XOS and CHOS leads to a strong transcriptional change for defense-related genes, and gene ontology (GO) enrichment analysis of RNAseq data revealed that a mixture of three oligosaccharide (oligo-mix) effectively activate the plants disease resistance. In practice, treatment of the oligo-mix enhanced the resistance of tomato to powdery mildew, but plant growth was not inhibited but rather tended to be promoted, providing evidence that mixed oligosaccharides have beneficial effects on improving disease resistance in plants, making them a promising class of compounds for practical application.
DICTrank: The largest reference list of 1318 human drugs ranked by risk of drug-induced cardiotoxicity using FDA labeling
Authors: Qu Yanyan , Li Ting , Liu Zhichao , Li Dongying , Tong Weida 
Published: July 2023

AbstractDrug-induced cardiotoxicity (DICT) is one of the leading causes of drug attrition in clinical trials or withdrawal from the market. Many studies have been conducted to detect DICT in the early stage of drug development and clinical diagnosis, but the success is limited, as evident by the high attrition rate at all clinical phases due to DICT. Most of these efforts, if not all, have focused on specific adverse events and/or mechanisms associated with DICT, such as QT prolongation and hERG-related cardiotoxicity. However, given the broad spectrum of cardiotoxicity, it is necessary to develop a reference drug list with a systematic annotation of DICT potential across a large number of drugs and drug classes. Such a list is essential for developing effective DICT diagnostic biomarkers and early prediction strategies using new approach methods (NAMs), including artificial intelligence (AI). By utilizing labeling documents for FDA (U.S. Food and Drug Administration)-approved drugs, we developed a drug classification scheme to prioritize drugs based on their DICT potential. This resulted in DICTrank, which is the largest dataset of drugs annotated with ranked DICT risk in humans. DICTrank categorizes drugs into four categories of DICT concerns by integrating DICT severity and labeling content. The dataset consists of 1318 drugs, classified as follows: Most-DICT-Concern (341), Less-DICT-Concern (528), No-DICT-Concern (343), and Ambiguous-DICT-Concern (106; lacking sufficient information in the labeling document to determine cardiotoxicity potential). DICTrank covers a wide range of drug therapeutic categories. Using this extensive DICT dataset, we discovered that several therapeutic categories were significantly enriched with drugs of Most-DICT-Concern as well as the association of daily dose with drug class. These categories include antineoplastic agents, sex hormones and modulators of the genital system, anti-inflammatory and antirheumatic products, beta-blocking agents, and cardiac therapy. DICTrank represents the largest drug list for DICT to date, and it could contribute to the development of NAMs and AI models for the early identification of DICT risk during drug development and beyond.
The PHB Granule Biogenesis Pathway inCaulobacter
Authors: de Koning Edward A. , Panjalingam Mayura , Tran Jessica , Eckhart Michael R. , Dahlberg Peter D. , Shapiro Lucy 
Published: July 2023

AbstractPHB granules are bacterial organelles that store excess carbohydrates in the form of water-insoluble polyhydroxybutyrate (PHB). The PHB polymerase, phasin (a small amphipathic protein), and active PHB synthesis are essential for the formation of mature PHB granules inCaulobacter crescentus. Granule formation was found to be initiated by the condensation of self-associating PHB polymerase-GFP into foci, closely followed by the recruitment and condensation of phasin-mCherry. Following the active synthesis of PHB and granule maturation, the polymerase dissociates from mature granules and the PHB depolymerase is recruited to the granule. The polymerase directly binds phasinin vitrothrough its intrinsically disordered N-terminal domain. Thus, granule biogenesis is initiated and controlled by the action of a PHB polymerase and an associated helper protein, phasin, that together synthesize the hydrophobic granule content while forming the granule’s protein boundary.ImportanceLike eukaryotes, bacteria organize their cytoplasm in subcellular compartments. These bacterial compartments can be membrane-bound (e.g. magnetosomes), or membraneless with protein-encased shells (e.g. carboxysomes). Here we investigate howCaulobacterforms membrane-less compartments that store the water-insoluble carbohydrate polymer polyhydroxybutyrate (PHB). A PHB polymerase is essential for granule biogenesis and we observed a direct interaction with the granule associated protein phasin through the disordered N-terminus of the polymerase. We found that PHB granules form by sequential recruitment of key proteins, beginning with the polymerase, and that the granule composition changes as these organelles mature.
Myosin XV is a negative regulator of signaling filopodia during long-range lateral inhibition
Authors: Clements Rhiannon , Smith Tyler , Cowart Luke , Zhumi Jennifer , Sherrod Alan , Cahill Aidan , Hunter Ginger L 
Published: July 2023

AbstractThe self-organization of cells during development is essential for the formation of healthy tissues, and requires the coordination of cell activities at local scales. Cytonemes, or signaling filopodia, are dynamic actin-based cellular protrusions that allow cells to engage in contact mediated signaling at a distance. While signaling filopodia have been shown to support several signaling paradigms during development, less is understood about how these protrusions are regulated. We investigated the role of the plus-end directed, unconventional MyTH4-FERM myosins in regulating signaling filopodia during sensory bristle patterning on the dorsal thorax of the fruit fly Drosophila melanogaster. We found that Myosin XV is required for regulating signaling filopodia dynamics and, as a consequence, lateral inhibition more broadly throughout the patterning epithelium. We found that Myosin XV is required for limiting the length and number of signaling filopodia generated by bristle precursor cells. Cells with additional and longer signaling filopodia due to loss of Myosin XV are not signaling competent, due to altered levels of Delta ligand and Notch receptor along their lengths. We conclude that Myosin XV acts to negatively regulate signaling filopodia, as well as promote the ability of signaling filopodia to engage in long-range Notch signaling. Since Myosin XV is present across several vertebrate and invertebrate systems, this may have significance for other long-range signaling mechanisms.