bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamical Network Stability Analysis of Multiple Biological Ages Provides a Framework for Understanding the Aging Process
Authors: Pridham Glen , Rutenberg Andrew D
Published: January 2024

Widespread interest in nondestructive biomarkers of aging has led to a multitude of biological ages that each proffers a “true” health-adjusted individual age. Although each measure provides salient information on the aging process, they are each univariate, in contrast to the “hallmark” and “pillar” theories of aging, which are explicitly multidimensional, multicausal, and multiscale. Fortunately, multiple biological ages can be systematically combined into a multidimensional network representation. The interaction network between these biological ages permits analysis of the multidimensional effects of aging, as well as quantification of causal influences during both natural aging and, potentially, after anti-aging intervention. The behavior of the system as a whole can then be explored using dynamical network stability analysis, which identifies new, efficient biomarkers that quantify long-term resilience scores on the timescale between measurements (years). We demonstrate this approach using a set of 8 biological ages from the longitudinal Swedish Adoption/Twin Study of Aging (SATSA). After extracting an interaction network between these biological ages, we observed that physiological age, a proxy for cardiometabolic health, serves as a central node in the network, implicating it as a key vulnerability for slow, age-related decline. We furthermore show that while the system as a whole is stable, there is a weakly stable direction along which recovery is slow—on the timescale of a human lifespan. This slow direction provides an aging biomarker, which correlates strongly with chronological age and predicts longitudinal decline in health—suggesting that it estimates an important driver of age-related changes.
Vulture: cloud-enabled scalable mining of microbial reads in public scRNA-seq data
Authors: Chen Junyi , Yin Danqing , Wong Harris Y H , Duan Xin , Yu Ken H O , Ho Joshua W K
Published: January 2024

The rapidly growing collection of public single-cell sequencing data has become a valuable resource for molecular, cellular, and microbial discovery. Previous studies mostly overlooked detecting pathogens in human single-cell sequencing data. Moreover, existing bioinformatics tools lack the scalability to deal with big public data. We introduce Vulture, a scalable cloud-based pipeline that performs microbial calling for single-cell RNA sequencing (scRNA-seq) data, enabling meta-analysis of host–microbial studies from the public domain. In our benchmarking experiments, Vulture is 66% to 88% faster than local tools (PathogenTrack and Venus) and 41% faster than the state-of-the-art cloud-based tool Cumulus, while achieving comparable microbial read identification. In terms of the cost on cloud computing systems, Vulture also shows a cost reduction of 83% ($12 vs. ${\$}$70). We applied Vulture to 2 coronavirus disease 2019, 3 hepatocellular carcinoma (HCC), and 2 gastric cancer human patient cohorts with public sequencing reads data from scRNA-seq experiments and discovered cell type–specific enrichment of severe acute respiratory syndrome coronavirus 2, hepatitis B virus (HBV), and Helicobacter pylori–positive cells, respectively. In the HCC analysis, all cohorts showed hepatocyte-only enrichment of HBV, with cell subtype-associated HBV enrichment based on inferred copy number variations. In summary, Vulture presents a scalable and economical framework to mine unknown host–microbial interactions from large-scale public scRNA-seq data. Vulture is available via an open-source license at https://github.com/holab-hku/Vulture.
A cross-sectional study of Australian teachers’ health: are work-related factors associated with lifestyle behaviours?
Authors: Corbett Lucy , Phongsavan Philayrath , Okely Anthony D , Peralta Louisa R , Bauman Adrian
Published: January 2024

Teacher’s lifestyle behaviours are important because they lead to positive health outcomes for teachers themselves and because teachers model behaviour to their students. This cross-sectional study examined the lifestyle behaviours of a large sample of teachers in New South Wales (NSW), Australia and assessed the association between work-related factors and lifestyle behaviours. From February to October 2021, data were collected on the lifestyle behaviours, work-related factors and socio-demographics of primary and secondary school teachers in NSW, via an online survey. Associations between individual work-related factors and lifestyle behaviours were modelled using logistic regression and adjusted for sex, age, number of children and geographic location. Most of our survey sample (n = 1136) were women (75%) and 53% were reported as having overweight or obesity. Only 23% of teachers met the recommended physical activity guidelines, 39% met fruit intake guidelines, 9% met vegetable intake guidelines and 58% met healthy sleep guidelines. Most teachers (78%) met the recommendation of sugar-sweetened beverage consumption, 89% were not current smokers, but only 46% met the recommended alcohol consumption guidelines. Hours worked, teaching load, school sector and teacher role were associated with one or more lifestyle behaviours after adjusting for the demographic variables. This study highlights the need for additional support to improve the health-related behaviours of teachers in NSW. Policymakers should recognize the negative impact of high workloads on teachers’ health-related behaviours, increasing their risk of chronic disease.
The endometrial microbiota and early pregnancy loss
Authors: Odendaal Joshua , Black Naomi , Bennett Phillip R , Brosens Jan , Quenby Siobhan , MacIntyre David A
Published: January 2024

The human endometrium is a dynamic entity that plays a pivotal role in mediating the complex interplay between the mother and developing embryo. Endometrial disruption can lead to pregnancy loss, impacting both maternal physical and psychological health. Recent research suggests that the endometrial microbiota may play a role in this, although the exact mechanisms are still being explored, aided by recent technological advancements and our growing understanding of host immune responses. Suboptimal or dysbiotic vaginal microbiota, characterized by increased microbial diversity and reduced Lactobacillus dominance, has been associated with various adverse reproductive events, including miscarriage. However, the mechanisms linking the lower reproductive tract microbiota with pregnancy loss remain unclear. Recent observational studies implicate a potential microbial continuum between the vaginal and endometrial niche in patients with pregnancy loss; however, transcervical sampling of the low biomass endometrium is highly prone to cross-contamination, which is often not controlled for. In this review, we explore emerging evidence supporting the theory that a dysbiotic endometrial microbiota may modulate key inflammatory pathways required for successful embryo implantation and pregnancy development. We also highlight that a greater understanding of the endometrial microbiota, its relationship with the local endometrial microenvironment, and potential interventions remain a focus for future research.
Peripheral voices: women in international trade scholarship
Authors: Muzaka Valbona , Scott James
Published: January 2024

We ask how women are faring in the field of international trade both as knowledge producers and as policy-makers, with a focus on the former. This is an important question in light of the increased, if belated, attention paid to the gendered impact of international trade rules and of the gendered nature of academia. Using article publishing as a proxy for international trade scholarship, we create a unique dataset consisting of trade-related articles published in the 27 most influential journals in the field during the past 20 years. Examining the gender balance of authors in our database reveals that, despite recent progress, women's voices are still peripheral in the field, comprising just 31.5 percent of authors in the past five years. We find no reasons to believe this is a peculiarity of knowledge creation in the field of international trade. Rather, the analysis suggests that it is the highly gendered nature of the broad fields of International Relations and International Political Economy that explains the gender imbalance we find. Looking ahead, if we are serious about addressing gender imbalances in international trade policy-making and knowledge production, new knowledge and strategies are needed that address the structural reasons that contribute to the arbitrary but very real gender inequalities both in academia and policy-making. Ensuring women scholars and policy-makers are fully represented in formulating and implementing these strategies is a basic, even if insufficient, precondition for their success. Only after the weaknesses and hurdles are addressed will the deterrence and defence of the region attain a fully credible level.
Index of Minimal Hypersurfaces in Real Projective Spaces
Authors: Chen Shuli
Published: January 2024

We prove that for an embedded unstable one-sided minimal hypersurface of the $(n+1)$-dimensional real projective space, the Morse index is at least $n+2$, and this bound is attained by the cubic isoparametric minimal hypersurfaces. We also show that there exist closed embedded two-sided minimal surfaces in the 3-dimensional real projective space of each odd index by computing the index of the Lawson surfaces.
Unraveling the Immune Signature of Herpes Zoster: Insights Into the Pathophysiology and Human Leukocyte Antigen Risk Profile
Authors: Vandoren Romi , Boeren Marlies , Schippers Jolien , Bartholomeus Esther , Mullan Kerry , Michels Nele , Aerts Olivier , Leysen Julie , Bervoets An , Lambert Julien , Leuridan Elke , Wens Johan , Peeters Karin , Emonds Marie-Paule , Jansens Hilde , Casanova Jean-Laurent , Bastard Paul , Suls Arvid , Van Tendeloo Viggo , Ponsaerts Peter , Delputte Peter , Ogunjimi Benson , Laukens Kris , Meysman Pieter
Published: January 2024

The varicella-zoster virus (VZV) infects >95% of the population. VZV reactivation causes herpes zoster (HZ), known as shingles, primarily affecting the elderly and individuals who are immunocompromised. However, HZ can occur in otherwise healthy individuals. We analyzed the immune signature and risk profile in patients with HZ using a genome-wide association study across different UK Biobank HZ cohorts. Additionally, we conducted one of the largest HZ human leukocyte antigen association studies to date, coupled with transcriptomic analysis of pathways underlying HZ susceptibility. Our findings highlight the significance of the major histocompatibility complex locus for HZ development, identifying 5 protective and 4 risk human leukocyte antigen alleles. This demonstrates that HZ susceptibility is largely governed by variations in the major histocompatibility complex. Furthermore, functional analyses revealed the upregulation of type I interferon and adaptive immune responses. These findings provide fresh molecular insights into the pathophysiology and activation of innate and adaptive immune responses triggered by symptomatic VZV reactivation.
Mucosal Immunity to Poliovirus in Children 0–15 Years of Age: A Community-Based Study in Karachi, Pakistan in 2019
Authors: Saleem Ali Faisal , Kazi Zaubina Umar , Zehra Syeda Mahjabeen , Parkar Sadia , Macklin Grace , Sifontes Giovanna , Mainou Bernardo A , Alam Masroor , Lopez Cavestany Rocio , Mach Ondrej
Published: January 2024

This study assesses poliovirus type 1 (PV1) immunity in children to inform the contribution of mucosal immunity in and prevention of poliovirus circulation. A community-based study was conducted in periurban Karachi, Pakistan. Randomly selected children (0–15 years of age) received oral poliovirus vaccine (OPV) challenge dose. Blood and stool samples were collected at several time points and evaluated for polio-neutralizing antibodies and serotype-specific poliovirus, respectively. Eighty-one of 589 (14%) children excreted PV1 7 days post-OPV challenge; 70 of 81 (86%) were seropositive at baseline. Twelve of 610 (2%) were asymptomatic wild poliovirus type 1 (WPV1) excretors. Most poliovirus excretors had humoral immunity, suggesting mucosal immunity in these children likely waned or never developed. Without mucosal immunity, they are susceptible to poliovirus infection, shedding, and transmission. Asymptomatic WPV1 excretion suggests undetected poliovirus circulation within the community.
Metabolic and phylogenetic diversity in the phylum Nitrospinota revealed by comparative genome analyses
Authors: Kop Linnea F M , Koch Hanna , Jetten Mike S M , Daims Holger , Lücker Sebastian
Published: January 2024

The most abundant known nitrite-oxidizing bacteria in the marine water column belong to the phylum Nitrospinota. Despite their importance in marine nitrogen cycling and primary production, there are only few cultured representatives that all belong to the class Nitrospinia. Moreover, although Nitrospinota were traditionally thought to be restricted to marine environments, metagenome-assembled genomes have also been recovered from groundwater. Over the recent years, metagenomic sequencing has led to the discovery of several novel classes of Nitrospinota (UBA9942, UBA7883, 2-12-FULL-45-22, JACRGO01, JADGAW01), which remain uncultivated and have not been analyzed in detail. Here, we analyzed a nonredundant set of 98 Nitrospinota genomes with focus on these understudied Nitrospinota classes and compared their metabolic profiles to get insights into their potential role in biogeochemical element cycling. Based on phylogenomic analysis and average amino acid identities, the highly diverse phylum Nitrospinota could be divided into at least 33 different genera, partly with quite distinct metabolic capacities. Our analysis shows that not all Nitrospinota are nitrite oxidizers and that members of this phylum have the genomic potential to use sulfide and hydrogen for energy conservation. This study expands our knowledge of the phylogeny and potential ecophysiology of the phylum Nitrospinota and offers new avenues for the isolation and cultivation of these elusive bacteria.
Taxonomic and functional stability overrules seasonality in polar benthic microbiomes
Authors: Miksch Sebastian , Orellana Luis H , Oggerin de Orube Monike , Vidal-Melgosa Silvia , Solanki Vipul , Hehemann Jan-Hendrik , Amann Rudolf , Knittel Katrin
Published: January 2024

Coastal shelf sediments are hot spots of organic matter mineralization. They receive up to 50% of primary production, which, in higher latitudes, is strongly seasonal. Polar and temperate benthic bacterial communities, however, show a stable composition based on comparative 16S rRNA gene sequencing despite different microbial activity levels. Here, we aimed to resolve this contradiction by identifying seasonal changes at the functional level, in particular with respect to algal polysaccharide degradation genes, by combining metagenomics, metatranscriptomics, and glycan analysis in sandy surface sediments from Isfjorden, Svalbard. Gene expressions of diverse carbohydrate-active enzymes changed between winter and spring. For example, β-1,3-glucosidases (e.g. GH30, GH17, GH16) degrading laminarin, an energy storage molecule of algae, were elevated in spring, while enzymes related to α-glucan degradation were expressed in both seasons with maxima in winter (e.g. GH63, GH13_18, and GH15). Also, the expression of GH23 involved in peptidoglycan degradation was prevalent, which is in line with recycling of bacterial biomass. Sugar extractions from bulk sediments were low in concentrations during winter but higher in spring samples, with glucose constituting the largest fraction of measured monosaccharides (84% ± 14%). In porewater, glycan concentrations were ~18-fold higher than in overlying seawater (1107 ± 484 vs. 62 ± 101 μg C l−1) and were depleted in glucose. Our data indicate that microbial communities in sandy sediments digest and transform labile parts of photosynthesis-derived particulate organic matter and likely release more stable, glucose-depleted residual glycans of unknown structures, quantities, and residence times into the ocean, thus modulating the glycan composition of marine coastal waters.
Plankton community changes during the last 124 000 years in the subarctic Bering Sea derived from sedimentary ancient DNA
Authors: Buchwald Stella Z , Herzschuh Ulrike , Nürnberg Dirk , Harms Lars , Stoof-Leichsenring Kathleen R
Published: January 2024

Current global warming results in rising sea-water temperatures, and the loss of sea ice in Arctic and subarctic oceans impacts the community composition of primary producers with cascading effects on the food web and potentially on carbon export rates. This study analyzes metagenomic shotgun and diatom rbcL amplicon sequencing data from sedimentary ancient DNA of the subarctic western Bering Sea that records phyto- and zooplankton community changes over the last glacial–interglacial cycles, including the last interglacial period (Eemian). Our data show that interglacial and glacial plankton communities differ, with distinct Eemian and Holocene plankton communities. The generally warm Holocene period is dominated by picosized cyanobacteria and bacteria-feeding heterotrophic protists, while the Eemian period is dominated by eukaryotic picosized chlorophytes and Triparmaceae. By contrast, the glacial period is characterized by microsized phototrophic protists, including sea ice-associated diatoms in the family Bacillariaceae and co-occurring diatom-feeding crustaceous zooplankton. Our deep-time record of plankton community changes reveals a long-term decrease in phytoplankton cell size coeval with increasing temperatures, resembling community changes in the currently warming Bering Sea. The phytoplankton community in the warmer-than-present Eemian period is distinct from modern communities and limits the use of the Eemian as an analog for future climate scenarios. However, under enhanced future warming, the expected shift toward the dominance of small-sized phytoplankton and heterotrophic protists might result in an increased productivity, whereas the community’s potential of carbon export will be decreased, thereby weakening the subarctic Bering Sea’s function as an effective carbon sink.
Distinct microbial hydrogen and reductant disposal pathways explain interbreed variations in ruminant methane yield
Authors: Li Qiushuang , Ma Zhiyuan , Huo Jiabin , Zhang Xiumin , Wang Rong , Zhang Shizhe , Jiao Jinzhen , Dong Xiyang , Janssen Peter H , Ungerfeld Emilio M , Greening Chris , Tan Zhiliang , Wang Min
Published: January 2024

Ruminants are essential for global food security, but these are major sources of the greenhouse gas methane. Methane yield is controlled by the cycling of molecular hydrogen (H2), which is produced during carbohydrate fermentation and is consumed by methanogenic, acetogenic, and respiratory microorganisms. However, we lack a holistic understanding of the mediators and pathways of H2 metabolism and how this varies between ruminants with different methane-emitting phenotypes. Here, we used metagenomic, metatranscriptomic, metabolomics, and biochemical approaches to compare H2 cycling and reductant disposal pathways between low-methane-emitting Holstein and high-methane-emitting Jersey dairy cattle. The Holstein rumen microbiota had a greater capacity for reductant disposal via electron transfer for amino acid synthesis and propionate production, catalyzed by enzymes such as glutamate synthase and lactate dehydrogenase, and expressed uptake [NiFe]-hydrogenases to use H2 to support sulfate and nitrate respiration, leading to enhanced coupling of H2 cycling with less expelled methane. The Jersey rumen microbiome had a greater proportion of reductant disposal via H2 production catalyzed by fermentative hydrogenases encoded by Clostridia, with H2 mainly taken up through methanogenesis via methanogenic [NiFe]-hydrogenases and acetogenesis via [FeFe]-hydrogenases, resulting in enhanced methane and acetate production. Such enhancement of electron incorporation for metabolite synthesis with reduced methanogenesis was further supported by two in vitro measurements of microbiome activities, metabolites, and public global microbiome data of low- and high-methane-emitting beef cattle and sheep. Overall, this study highlights the importance of promoting alternative H2 consumption and reductant disposal pathways for synthesizing host-beneficial metabolites and reducing methane production in ruminants.
Cryptochrome PtCPF1 regulates high temperature acclimation of marine diatoms through coordination of iron and phosphorus uptake
Authors: Gao Shan , Yang Wenting , Li Xin , Zhou Lu , Liu Xuehua , Wu Songcui , Wang Lijun , Wang Guangce
Published: January 2024

Increasing ocean temperatures threaten the productivity and species composition of marine diatoms. High temperature response and regulation are important for the acclimation of marine diatoms to such environments. However, the molecular mechanisms behind their acclimation to high temperature are still largely unknown. In this study, the abundance of PtCPF1 homologs (a member of the cryptochrome-photolyase family in the model diatom Phaeodactylum tricornutum) transcripts in marine phytoplankton is shown to increase with rising temperature based on Tara Oceans datasets. Moreover, the expression of PtCPF1 in P. tricornutum at high temperature (26 °C) was much higher than that at optimum temperature (20 °C). Deletion of PtCPF1 in P. tricornutum disrupted the expression of genes encoding two phytotransferrins (ISIP2A and ISIP1) and two Na+/P co-transporters (PHATRDRAFT_47667 and PHATRDRAFT_40433) at 26 °C. This further impacted the uptake of Fe and P, and eventually caused the arrest of cell division. Gene expression, Fe and P uptake, and cell division were restored by rescue with the native PtCPF1 gene. Furthermore, PtCPF1 interacts with two putative transcription factors (BolA and TF IIA) that potentially regulate the expression of genes encoding phytotransferrins and Na+/P co-transporters. To the best of our knowledge, this is the first study to reveal PtCPF1 as an essential regulator in the acclimation of marine diatoms to high temperature through the coordination of Fe and P uptake. Therefore, these findings help elucidate how marine diatoms acclimate to high temperature.
Genomic basis of environmental adaptation in the widespread poly-extremophilic Exiguobacterium group
Authors: Shen Liang , Liu Yongqin , Chen Liangzhong , Lei Tingting , Ren Ping , Ji Mukan , Song Weizhi , Lin Hao , Su Wei , Wang Sheng , Rooman Marianne , Pucci Fabrizio
Published: January 2024

Delineating cohesive ecological units and determining the genetic basis for their environmental adaptation are among the most important objectives in microbiology. In the last decade, many studies have been devoted to characterizing the genetic diversity in microbial populations to address these issues. However, the impact of extreme environmental conditions, such as temperature and salinity, on microbial ecology and evolution remains unclear so far. In order to better understand the mechanisms of adaptation, we studied the (pan)genome of Exiguobacterium, a poly-extremophile bacterium able to grow in a wide range of environments, from permafrost to hot springs. To have the genome for all known Exiguobacterium type strains, we first sequenced those that were not yet available. Using a reverse-ecology approach, we showed how the integration of phylogenomic information, genomic features, gene and pathway enrichment data, regulatory element analyses, protein amino acid composition, and protein structure analyses of the entire Exiguobacterium pangenome allows to sharply delineate ecological units consisting of mesophilic, psychrophilic, halophilic-mesophilic, and halophilic-thermophilic ecotypes. This in-depth study clarified the genetic basis of the defined ecotypes and identified some key mechanisms driving the environmental adaptation to extreme environments. Our study points the way to organizing the vast microbial diversity into meaningful ecologically units, which, in turn, provides insight into how microbial communities adapt and respond to different environmental conditions in a changing world.
Bacteria use a catabolic patchwork pathway of apparently recent origin for degradation of the synthetic buffer compound TRIS
Authors: Holert Johannes , Borker Aron , Nübel Laura Lucia , Daniel Rolf , Poehlein Anja , Philipp Bodo
Published: January 2024

The synthetic buffer compound TRIS (2-amino-2-(hydroxymethyl)propane-1,3-diol) is used in countless applications, and no detailed information on its degradation has been published so far. Herein, we describe the discovery of a complete bacterial degradation pathway for TRIS. By serendipity, a Pseudomonas strain was isolated from sewage sludge that was able to grow with TRIS as only carbon and nitrogen source. Genome and transcriptome analyses revealed two adjacent gene clusters embedded in a mobile genetic element on a conjugative plasmid to be involved in TRIS degradation. Heterologous gene expression revealed cluster I to encode a TRIS uptake protein, a TRIS alcohol dehydrogenase, and a TRIS aldehyde dehydrogenase, catalyzing the oxidation of TRIS into 2-hydroxymethylserine. Gene cluster II encodes a methylserine hydroxymethyltransferase (mSHMT) and a d-serine dehydratase that plausibly catalyze the conversion of 2-hydroxymethylserine into pyruvate. Conjugational plasmid transfer into Pseudomonas putida KT2440 enabled this strain to grow with TRIS and with 2-hydromethylserine, demonstrating that the complete TRIS degradation pathway can be transmitted by horizontal gene transfer. Subsequent enrichments from wastewater purification systems led to the isolation of further TRIS-degrading bacteria from the Pseudomonas and Shinella genera carrying highly similar TRIS degradation gene clusters. Our data indicate that TRIS degradation evolved recently via gene recruitment and enzyme adaptation from multiple independent metabolic pathways, and database searches suggest that the TRIS degradation pathway is now globally distributed. Overall, our study illustrates how engineered environments can enhance the emergence of new microbial metabolic pathways in short evolutionary time scales.
Trojan horselike T6SS effector TepC mediates both interference competition and exploitative competition
Authors: Song Li , Xu Lei , Wu Tong , Shi Zhenkun , Kareem Hafiz Abdul , Wang Zhuo , Dai Qingyun , Guo Chenghao , Pan Junfeng , Yang Mingming , Wei Xiaomeng , Wang Yao , Wei Gehong , Shen Xihui
Published: January 2024

The type VI secretion system (T6SS) is a bacterial weapon capable of delivering antibacterial effectors to kill competing cells for interference competition, as well as secreting metal ion scavenging effectors to acquire essential micronutrients for exploitation competition. However, no T6SS effectors that can mediate both interference competition and exploitation competition have been reported. In this study, we identified a unique T6SS-1 effector in Yersinia pseudotuberculosis named TepC, which plays versatile roles in microbial communities. First, secreted TepC acts as a proteinaceous siderophore that binds to iron and mediates exploitative competition. Additionally, we discovered that TepC has DNase activity, which gives it both contact-dependent and contact-independent interference competition abilities. In conditions where iron is limited, the iron-loaded TepC is taken up by target cells expressing the outer membrane receptor TdsR. For kin cells encoding the cognate immunity protein TipC, TepC facilitates iron acquisition, and its toxic effects are neutralized. On the other hand, nonkin cells lacking TipC are enticed to uptake TepC and are killed by its DNase activity. Therefore, we have uncovered a T6SS effector, TepC, that functions like a “Trojan horse” by binding to iron ions to provide a valuable resource to kin cells, whereas punishing cheaters that do not produce public goods. This lure-to-kill mechanism, mediated by a bifunctional T6SS effector, may offer new insights into the molecular mechanisms that maintain stability in microbial communities.
Treatment, outcomes and characterization of pathogens in urinary tract infections caused by ESBL-producing Enterobacterales: a prospective multicentre study
Authors: Montelin Hanna , Camporeale Angela , Hallgren Anna , Angelin Martin , Hogvall Jonas , Östholm Balkhed Åse , Vading Malin , Giske Christian G , Tängdén Thomas ,   the Swedish ESBL study group, Angelin Martin , Bremell Daniel , Edenvik David , Eklund Cecilia , Eriksson Sofie , Hallgren Anna , Hallgren Helena , Hansson Jonas , Hellborg Thomas , Hjorton Hampus , Hogvall Jonas , Josephson Maria , Lenzen Julia , Lindqvist Eva , Löfgren Cecilia K , Montelin Hanna , Nauclér Pontus , Remén Maria , Settergren Bo , Tham Johan , Vading Malin , Wetterberg Jon , Balkhed Åse Östholm
Published: January 2024

Objectives

Treatment options for urinary tract infections (UTIs) caused by ESBL-producing Enterobacterales are limited. Moreover, evidence to support therapeutic decisions is lacking. This study assessed current treatment strategies and patient and pathogen characteristics in relation to clinical and microbiological outcomes.

Methods

Patients with UTI caused by ESBL-producing Enterobacterales were prospectively recruited by investigators at 15 infectious disease hospital departments. Data were collected on patient characteristics, treatments, clinical and microbiological cure 10–14 days after the end of treatment, and relapse within 3 months. Bacterial isolates were subjected to MIC determination and WGS.

Results

In total, 235 patients (107 febrile UTI, 128 lower UTI) caused by Escherichia coli (n = 223) and Klebsiella spp. (n = 12) were included. Clinical and microbiological cure rates were 83% and 64% in febrile UTI, and 79% and 65% in lower UTI. Great variability in treatments was observed, especially in oral therapy for febrile UTI. No difference was seen in clinical outcomes with piperacillin/tazobactam (n = 28) compared with carbapenems (n = 41). Pivmecillinam was frequently used in lower UTI (n = 62), and was also associated with high clinical cure rates when used as initial therapy (10/10) or follow-up (7/8) for febrile UTI. Recurrent infection, diabetes mellitus and urogenital disease were associated (P < 0.05) with clinical failure and relapse. In E. coli, ST131 was significantly associated with relapse, and haemolysin with microbiological failure or relapse.

Conclusions

Antibiotic treatments were highly variable. Patient and pathogen factors were identified as potential determinants of disease presentation and outcomes and may prove useful to guide individualized treatment and follow-up.
Fetal programming effect of rumen-protected methionine on primiparous Angus × Simmental offspring’s performance and skeletal muscle gene expression
Authors: Alfaro Gastón F , Rodning Soren P , Moisá Sonia J
Published: January 2024

Primiparous Angus × Simmental dams (n = 22) with an average body weight (BW) of 449 ± 32 kg of BW were divided based on two nutritional treatments: control (CTRL) and rumen-protected methionine (RPM). The control group received bermudagrass hay, corn gluten, and soybean hulls pellets supplementation (base diet); whereas the RPM group received the base diet in addition to 0.07% of DM of RPM at a fixed rate during the last trimester of gestation and the first ~80 d of lactation, in which calves (n = 17) were early weaned. Only male calves were included in this study. After weaning, calves born to RPM dams also received RPM from weaning (day 1) to day 100. Blood sampling and skeletal muscle biopsies for subsequent quantitative polymerase chain reaction (PCR) analysis were conducted on days 1, 25, 50, and 100 on calves. Quantitative PCR data were analyzed using GLIMMIX, and blood metabolites concentrations, BW, and body condition score (BCS) were analyzed using the MIXED procedure of SAS. There was no difference in maternal BW and BCS between treatments. Glucose and blood metabolites that served as biomarkers for liver health (e.g., aspartate transaminase, albumin, alkaline phosphatase, and alanine transaminase) were in the normal levels for all calves (P > 0.40). Calves in the RPM group had a greater expression of adipogenic genes (e.g., PPARG, LPL, and CEBPD) at day 100 compared with CTRL (P < 0.01). In addition, DNA methylation (DNMT1) and oxidative stress-related genes (SOD2 and NOS3) in the RPM group were upregulated at day 100 compared with CTRL (P < 0.01). These results may suggest that calves born to primiparous dams exposed to RPM supplementation are more prone to develop greater adipose tissue than CTRL calves. Furthermore, RPM supplementation may improve methylation processes, as shown by the upregulation of DNMT1. The results shown in our study aim at expanding the knowledge on fetal programming and early-life growth and development of beef cattle under supplementation with RPM.
Effect ofSaccharomyces cerevisiaePostbiotics and Essential Oil on Growth Performance and Intestinal Health of Weanling Pigs During K88 ETEC Infection
Authors: Yan Hui , Xing Qian , Xiao Xiarui , Yu Bing , He Jun , Mao Xiangbing , Yu Jie , Zheng Ping , Luo Yuheng , Wu Aimin , Pu Junning , Lu Ping , Wei Ming , Khafipour Ehsan , Chen Daiwen
Published: January 2024

Enterotoxigenic Escherichia coli (ETEC) is one of the major bacterial infections, causing substantial economic losses globally in the swine industry. This study aimed to investigate the impact of low Saccharomyces cerevisiae fermentation postbiotics (SCFP), high SCFP, essential oil (EO), or their combination on the growth performance and health of weanling pigs during ETEC infection. Forty-eight male weanling pigs were randomly allocated to five groups: 1) control group (CON—basal diet, n = 16); 2) low SCFP group (LSC—basal diet + 1.25 g/kg SCFP, n = 8); 3) high SCFP group (HSC—basal diet + 2 g/kg SCFP, n = 8); 4) essential oil group (EO—basal diet + 0.4 g/kg EO, n = 8); 5) the SCFP and EO combination group (SE—basal diet + 1.25 g/kg SCFP + 0.4 g/kg EO, n = 8). On day 15 of the trial, pigs in CON were divided into positive control (PC) and negative control (NC), and all pigs, except in NC, were challenged with ETEC. Under the normal condition, dietary LSC, HSC, EO, and EO all increased average daily gain (ADG) (P < 0.05), and decreased F:G ratio (P < 0.05) accompanied by decreased malondialdehyde (MDA) and increases in catalase (CAT), total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC) indicating enhanced anti-oxidative capacity, as well as decreased IL-2, IL-8, INF-γ, indicating mitigated systemic inflammation. During ETEC infection, all treatments alleviated ETEC-induced ADG reduction, diarrhea, damages in intestinal permeability and morphology, and down-regulation of tight junctions (Claudin1, ZO-1, and Occludin), while HSC and EO exhibited additional protections. All treatments increased CAT, T-SOD, and T-AOC, and decreased MDA in serum and jejunal mucosa at similar degrees (P < 0.05). Moreover, all treatments alleviated ETEC-induced inflammation as shown by decreased IL-6, TNF-α, INF-γ, and increased IL-4 and IL-10 in serum or jejunal mucosa (P < 0.05), and enhanced the immunity by increased serum IgG and mucosal sIgA (P < 0.05). HSC and SE further reduced mucosal INF-γ and TNF-α than LSC or EO aligning with their additional protection against diarrhea during ETEC infection. Additionally, the key gut bacteria (e.g., Terrisporobacter) related to the benefits of SCFP and EO were identified. In sum, all treatments enhanced growth performance and protected against ETEC-induced intestinal damage through the regulation of redox and immune homeostasis. HSP and SE offered extra protection during disease for their additional control of inflammation. Our study provided new insight into the use of feed additives in the context of animal health states.
Phenylalanine requirements using the direct amino acid oxidation technique, and the effects of dietary phenylalanine on food intake, gastric emptying, and macronutrient metabolism in adult cats
Authors: Lambie Jocelyn G , Pezzali Júlia G , Richards Taylor L , Ellis Jennifer L , Verbrugghe Adronie , Shoveller Anna K
Published: January 2024

Despite Phe being an indispensable amino acid for cats, the minimum Phe requirement for adult cats has not been empirically defined. The objective of study 1 was to determine the minimum Phe requirement, where Tyr is in excess, in adult cats using the direct amino acid oxidation (DAAO) technique. Four adult male cats were used in an 8 × 4 Latin rectangle design. Cats were adapted to a basal diet for 7 d, top dressed with Phe to meet 140% of the adequate intake (NRC, 2006. Nutrient requirements of dogs and cats. Washington, DC: Natl. Acad. Press). Cats were randomly assigned to one of eight experimental Phe diets (0.29%, 0.34%, 0.39%, 0.44%, 0.54%, 0.64%, 0.74%, and 0.84% Phe in the diet on a dry matter [DM] basis). Following 1 d of diet adaptation, individual DAAO studies were performed. During each DAAO study, cats were placed into individual indirect calorimetry chambers, and 75% of the cat’s daily meal was divided into 13 equal meals supplied with a dose of L-[1-13C]-Phe. Oxidation of L-[1-13C]-Phe (F13CO2) during isotopic steady state was determined from the enrichment of 13CO2 in breath. Competing models were applied using the NLMIXED procedure in SAS to determine the effects of dietary Phe on 13CO2. The mean population minimum requirement for Phe was estimated at 0.32% DM and the upper 95% population confidence limit at 0.59% DM on an energy density of 4,200 kcal of metabolizable energy/kg DM calculated using the modified Atwater factors. In study 2, the effects of a bolus dose of Phe (44 mg kg−1 BW) on food intake, gastric emptying (GE), and macronutrient metabolism were assessed in a crossover design with 12 male cats. For food intake, cats were given Phe 15 min before 120% of their daily food was offered and food intake was measured. Treatment, day, and their interaction were evaluated using PROC GLIMMIX in SAS. Treatment did not affect any food intake parameters (P > 0.05). For GE and macronutrient metabolism, cats were placed into individual indirect calorimetry chambers, received the same bolus dose of Phe, and 15 min later received 13C-octanoic acid (5 mg kg−1 BW) on 50% of their daily food intake. Breath samples were collected to measure 13CO2. The effect of treatment was evaluated using PROC GLIMMIX in SAS. Treatment did not affect total GE (P > 0.05), but cats receiving Phe tended to delay time to peak enrichment (0.05 < P ≤ 0.10). Overall, Phe at a bolus dose of 44 mg kg−1 BW had no effect on food intake, GE, or macronutrient metabolism. Together, these results suggest that the bolus dose of Phe used may not be sufficient to elicit a GE response, but a study with a greater number of cats and greater food intake is warranted.
Gift Giving in Enduring Dyadic Relationships: The Micropolitics of Mother–Daughter Gift Exchange
Authors: Liu Chihling , Kozinets Robert V , Patterson Anthony , Zhao Xin
Published: January 2024

This article investigates the dynamics of long-term gift exchange between British mothers and their adult daughters, delving into the processes behind dyadic gift giving. Through 54 comprehensive interviews, we elaborate the micropolitics that characterize these dynamics. Micropolitics refers to the subtle, everyday interactions, including gift exchange, that shape the ongoing negotiation of roles and the management of conflict or consensus within relationships. The study uncovers how these micropolitics manifest through four distinct processes of gift exchange: confirming, endorsing, connoting, and commanding. Gifts emerge as key instruments in this negotiation, serving as a medium for the reciprocal regulation of role behavior concerning gender, identity, and both endo-dyadic (within the dyad) and exo-dyadic (outside the dyad) roles. In contrast to previous research that adopts a synchronic (snapshot) approach to gift giving, our diachronic (over time) perspective emphasizes how power dynamics, intent, and identity politics evolve to sustain and transform relationships. Our findings illustrate the important communicative and power-laden processes of gift exchange in enduring relations, explaining why even unwanted gifts can have significant bonding value. Our study offers fresh perspectives on the continuous evolution of relationship and role dynamics, as viewed through the practices of gift exchange.
Descriptive Analysis of Community Based Needs among Asylum Seekers in the Greater Rhode Island Area before and after COVID-19: Evidence from a Student-Run Asylum Clinic
Authors: Angenent-Mari Victoria , Kasthuri Viknesh S , Montoya Hannah , Toll Elizabeth
Published: January 2024

The Brown Human Rights Asylum Clinic (BHRAC) is a medical-student-run asylum clinic which provides pro-bono medical and psychological affidavits for people in immigration proceedings. At the time of the evaluations for affidavits, a BHRAC student administers a Social Determinants of Health (SDoH) screener, evaluating clients for access to healthcare and social needs such as assistance with utilities payments and housing. Medical students follow up later and connect clients with trusted resources. This descriptive analysis reviews the population demographics; demonstrates common resource requests within our population before and after the start of COVID-19; and suggests possible improvements to our clinic model. Of clients who completed the SDoH screening, 89 per cent requested at least one form of assistance; their most common request was for mental health services, followed by English classes and medical services. No change to community resource request trends appeared before and after the start of COVID-19. Barriers encountered included delays and difficulty administering the survey to clients who did not speak English or Spanish, the ethical concern of the evaluation team also offering community resources for future care, and the changes resulting from annual rotation in BHRAC student leadership.
Dynamics of dimorphic workers of Constrictotermes cyphergaster (Blattodea: Termitidae) during nest repair
Authors: Andrade Marllon Rinaldo de Lima , Eloi Igor , de Oliveira Mário Herculano , Bezerra-Gusmão Maria Avany
Published: January 2024

Termite nest repairs are considered a defensive conduct as they reduce the colony’s exposure to the external environment. Repair activities are carried out by worker castes that can be polymorphic, representing a relationship between polymorphism and divisions of functions that can enhance task completion. Repairs are influenced by the extent of damage, nest volume, and the population dynamics of the building species, which regulate the recruitment of individuals for this activity. Our objective was to verify the performances (recruitment for repair) of dimorphic workers of Constrictotermes cyphergaster (Silvestri, 1901) during the damage repair activities performed on the external walls of termite nests of different sizes. We found a significant difference in the presence of dimorphic workers that performed repairs, with greater recruitment of the small morphotype, and observed an alternation of morphotypes between initial and final repair activities, with no influence of morphotype on the replacement pattern. Our results also showed that the total number of recruited workers decreased with increasing nest volume. These results help to better understand the social organization of a Nasutitermitinae termite species and the strategies adopted to protect its colonies.
Propionate functions as a feeding state–dependent regulatory metabolite to counter proinflammatory signaling linked to nutrient load and obesity
Authors: Han Kim , Meadows Allison M , Rodman Matthew J , Russo Anna Chiara , Sharma Rahul , Singh Komudi , Hassanzadeh Shahin , Dagur Pradeep K , Huffstutler Rebecca D , Krause Fynn N , Griffin Julian L , Baumer Yvonne , Powell-Wiley Tiffany M , Sack Michael N
Published: January 2024

Generally, fasting and refeeding confer anti- and proinflammatory effects, respectively. In humans, these caloric-load interventions function, in part, via regulation of CD4+ T cell biology. However, mechanisms orchestrating this regulation remain incomplete. We employed integrative bioinformatics of RNA sequencing and high-performance liquid chromatography–mass spectrometry data to measure serum metabolites and gene expression of peripheral blood mononuclear cells isolated from fasting and refeeding in volunteers to identify nutrient-load metabolite-driven immunoregulation. Propionate, a short chain fatty acid (SCFA), and the SCFA-sensing G protein–coupled receptor 43 (ffar2) were coordinately and inversely regulated by fasting and refeeding. Propionate and free fatty acid receptor agonists decreased interferon-γ and interleukin-17 and significantly blunted histone deacetylase activity in CD4+ T cells. Furthermore, propionate blunted nuclear factor κB activity and diminished interleukin-6 release. In parallel, propionate reduced phosphorylation of canonical T helper 1 (TH1) and TH17 regulators, STAT1 and STAT3, respectively. Conversely, knockdown of free fatty acid receptors significantly attenuated the anti-inflammatory role of propionate. Interestingly, propionate recapitulated the blunting of CD4+ TH cell activation in primary cells from obese individuals, extending the role of this metabolite to a disease associated with low-grade inflammation. Together, these data identify a nutrient-load responsive SCFA–G protein–coupled receptor linked pathway to regulate CD4+ TH cell immune responsiveness.
The Effective Use of Economics in the EU Digital Markets Act
Authors: Fletcher Amelia , Crémer Jacques , Heidhues Paul , Kimmelman Gene , Monti Giorgio , Podszun Rupprecht , Schnitzer Monika , Scott Morton Fiona , de Streel Alexandre
Published: January 2024

Economic thinking and analysis lie at the heart of the objectives and the design of the EU Digital Markets Act (DMA). However, the design of the DMA reflects a very deliberate—and reasonable—intention to ensure clarity, speed, administrability, and enforceability. In doing so, this pro-competitive regulation omits several elements of standard competition law where economics has typically played a key role. Nonetheless, we believe that economic insights and analysis—including behavioural economic thinking—will continue to play an important role in enabling the DMA to achieve its ambitious and laudable goals, albeit in a somewhat different way.
Natural products derived from herbs as promising source for diarrhea predominant-irritable bowel syndrome via gut microbiota–serotonin pathway
Authors: Zhang Mengmeng , Dang Ming , Li Yao , Wei PeiFeng , Zhao Chongbo , Dong Taiwei
Published: January 2024

Objective

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders, with diarrhea predominant IBS (IBS-D) as the most common subtype. Increasing evidence reported that the gut microbiota-mediated serotonin pathway plays a crucial role in the pathogenesis of IBS-D. In this study, potential herbal medicine, plant extracts and its monomers that can be employed as the candidate molecules for IBS-D through gut microbiota-mediated serotonin pathway were reviewed.

Key findings

The bacteria indigenous to gut microbiota regulates serotonin pathway, mainly increasing tryptophan hydroxylase (TPH) and decreasing serotonin reuptake transporter (SERT), by activating cyclooxygenase/prostaglandin E2 (COX/PGE2) signaling. It further accelerated gastrointestinal motility and visceral hyperalgesia. Herbal medicine prescription including Tongxie yaofang and Shugan decoction, as well as some monomers of flavonoid and polyphenol compounds can be regarded as the potential agents for IBS-D. The predominate mechanisms were related to regulating serotonin pathway by driving on the specific bacterial abundance (such as Firmicutes and Bacteroidetes). However, there are few reports on which specific bacteria species play a regulatory role in serotonin pathway, and most of these effective agents were only evidenced by preclinical studies. We hope this review will provide some useful directions for the treatment strategy of IBS-D.