An Improved Assessment Method to Estimate (Poly)phenol Intake in Adults with Chronic Pancreatitis.

BACKGROUND: Insights into (poly)phenol exposure represent a modifiable factor that may modulate inflammation in chronic pancreatitis (CP), yet intake is poorly characterized and methods for assessment are underdeveloped. AIMS: The aims are to develop and test a method for estimating (poly)phenol intake from a 90-day food frequency questionnaire (FFQ) using the Phenol-Explorer database and determine associations with dietary patterns in CP patients versus controls via analysis of previously collected cross-sectional data. METHODS: Fifty-two CP patients and 48 controls were recruited from an ambulatory clinic at a large, academic institution. To assess the feasibility of the proposed methodology for estimating dietary (poly)phenol exposure, a retrospective analysis of FFQ data was completed. Mann-Whitney U tests were used to compare (poly)phenol intake by group; Spearman correlations and multivariable-adjusted log-linear associations were used to compare (poly)phenol intakes with dietary scores within the sample. RESULTS: Estimation of (poly)phenol intake from FFQs was feasible and produced estimates within a range of intake previously reported. Total (poly)phenol intake was significantly lower in CP vs controls (463 vs. 567mg/1000kcal; p = 0.041). In adjusted analyses, higher total (poly)phenol intake was associated with higher HEI-2015 (r = 0.34, p < 0.001), aMED (r = 0.22, p = 0.007), EDIH (r = 0.29, p < 0.001), and EDIP scores (r = 0.35, p < 0.001), representing higher overall diet quality and lower insulinemic and anti-inflammatory dietary potentials, respectively. CONCLUSIONS: Using enhanced methods to derive total (poly)phenol intake from an FFQ is feasible. Those with CP have lower total (poly)phenol intake and less favorable dietary pattern indices, thus supporting future tailored dietary intervention studies in this population.

An efficient pyrrolysyl-tRNA synthetase for economical production of MeHis-containing enzymes.

Genetic code expansion has emerged as a powerful tool in enzyme design and engineering, providing new insights into sophisticated catalytic mechanisms and enabling the development of enzymes with new catalytic functions. In this regard, the non-canonical histidine analogue Nδ-methylhistidine (MeHis) has proven especially versatile due to its ability to serve as a metal coordinating ligand or a catalytic nucleophile with a similar mode of reactivity to small molecule catalysts such as 4-dimethylaminopyridine (DMAP). Here we report the development of a highly efficient aminoacyl tRNA synthetase (G1PylRSMIFAF) for encoding MeHis into proteins, by transplanting five known active site mutations from Methanomethylophilus alvus (MaPylRS) into the single domain PylRS from Methanogenic archaeon ISO4-G1. In contrast to the high concentrations of MeHis (5-10 mM) needed with the Ma system, G1PylRSMIFAF can operate efficiently using MeHis concentrations of ∼0.1 mM, allowing more economical production of a range of MeHis-containing enzymes in high titres. Interestingly G1PylRSMIFAF is also a 'polyspecific' aminoacyl tRNA synthetase (aaRS), enabling incorporation of five different non-canonical amino acids (ncAAs) including 3-pyridylalanine and 2-fluorophenylalanine. This study provides an important step towards scalable production of engineered enzymes that contain non-canonical amino acids such as MeHis as key catalytic elements.

Standard rodent diets differentially impact alcohol consumption, preference, and gut microbiome diversity.

Alcohol use disorder (AUD) is a complex and widespread disease with limited pharmacotherapies. Preclinical animal models of AUD use a variety of voluntary alcohol consumption procedures to recapitulate different phases of AUD, including binge alcohol consumption and dependence. However, voluntary alcohol consumption in mice is widely variable, making it difficult to reproduce results across labs. Accumulating evidence indicates that different brands of commercially available rodent chow can profoundly influence alcohol intake. In this study, we investigated the effects of three commercially available and widely used rodent diet formulations on alcohol consumption and preference in C57BL/6 J mice using the 24 h intermittent access procedure. The three brands of chow tested were LabDiet 5,001 (LD5001), LabDiet 5,053 (LD5053), and Teklad 2019S (TL2019S) from two companies (Research Diets and Envigo, respectively). Mice fed LD5001 and LD5053 displayed higher levels of alcohol consumption and preference compared to mice fed TL2019S. We also found that alcohol consumption and preference could be rapidly switched by changing the diet 48 h prior to alcohol administration. Sucrose, saccharin, and quinine preferences were not altered, suggesting that the diets did not alter sweet and bitter taste perception. We also found that mice fed LD5001 displayed increased quinine-resistant alcohol intake compared to mice fed TL2019S, suggesting that diets could influence the development of compulsive behaviors such as alcohol consumption. We profiled the gut microbiome of water- and alcohol-drinking mice that were maintained on different diets and found significant differences in bacterial alpha- and beta-diversities, which could impact the gut-brain axis signaling and alcohol consumption.

Hepatocellular RECK as a Critical Regulator of Metabolic Dysfunction-associated Steatohepatitis Development.

BACKGROUND & AIMS: Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is an extracellular matrix regulator with anti-fibrotic effects. However, its expression and role in metabolic dysfunction-associated steatohepatitis (MASH) and hepatic fibrosis are poorly understood. METHODS: We generated a novel transgenic mouse model with RECK overexpression specifically in hepatocytes to investigate its role in Western diet (WD)-induced liver disease. Proteomic analysis and in vitro studies were performed to mechanistically link RECK to hepatic inflammation and fibrosis. RESULTS: Our results show that RECK expression is significantly decreased in liver biopsies from human patients diagnosed with MASH and correlated negatively with severity of metabolic dysfunction-associated steatotic liver disease (MASLD) and fibrosis. Similarly, RECK expression is downregulated in WD-induced MASH in wild-type mice. Hepatocyte-RECK overexpression significantly reduced hepatic pathology in WD-induced liver injury. Proteomic analysis highlighted changes in extracellular matrix and cell-signaling proteins. In vitro mechanistic studies linked RECK induction to reduced ADAM10 (a disintegrin and metalloproteinase domain-containing protein 10) and ADAM17 activity, amphiregulin release, epidermal growth factor receptor activation, and stellate cell activation. CONCLUSION: Our in vivo and mechanistic in vitro studies reveal that RECK is a novel upstream regulator of inflammation and fibrosis in the diseased liver, its induction is hepatoprotective, and thus highlights its potential as a novel therapeutic in MASH.

Imagery-Focused Therapy for Visual Hallucinations: A Case Series.

INTRODUCTION: Visual hallucinations (VH) are more common than previously thought and are linked to higher levels of distress and disability in people with a psychotic illness. Despite this, scant attention has been given to VHs in the clinical literature, and the few therapy case series of cognitive behavioural therapy (CBT) published to date have not demonstrated reliable change. In other areas of clinical research, problematic mental imagery has been found to be more strongly related to negative affect in psychological disorders than negative linguistic thinking, and imagery focused techniques have commonly been found to improve the outcomes in CBT trials. Given VHs have many similarities with visual mental imagery and many of the distressing beliefs associated with VHs targeted in CBT are maintained by accompanying mental imagery (i.e., imaging a hallucinated figure attacking them), it seems plausible that an imagery-focused approach to treating VHs may be most effective. METHODS: The current study is a multiple baseline case series (N = 11) of a 10-session imagery-focused therapy for VH in a transdiagnostic sample. RESULTS: The study had good attendance and feedback, no adverse events and only one [seemly unrelated] drop-out, suggesting good feasibility, safety and acceptability. The majority of clients reported reduction on both full-scale measures (administered at 3 baselines, midtherapy, posttherapy and 3-month follow-up) and weekly measures of VH severity and distress, ranging from medium to large effect sizes. CONCLUSIONS: The case series suggests that an imagery-focused approach to treating VHs may be beneficial, with a recommendation for more rigorous clinical trials to follow.

Variation in fine-scale water table depth drives abundance of a unique semi-terrestrial crayfish species.

With anthropogenic changes altering the environment and the subsequent decline of natural habitats, it can be challenging to predict essential habitats for elusive and difficult to study taxa. Primary burrowing crayfish are one such group due to the complexity in sampling their semi-terrestrial, subterranean habitat. Sampling burrows usually requires a labor-intensive, time-consuming excavation or trapping process. However, limited information on burrowing crayfish suggests that fine-scale habitat variation may drive burrowing crayfish habitat choice. This project aimed to evaluate the fine-scale habitat characteristics that influence burrowing crayfish presence and abundance at a large, restored-remnant grassland preserve in north-central Illinois. We documented burrow abundance and quadrat-specific habitat variables such as root biomass, canopy cover, apparent seasonal high-water table (water table) depth and dominant vegetation at sites with and without burrowing crayfish populations. Data was recorded at every quadrat and analyzed using generalized linear mixed models. A total of 21 models were created to determine what habitat variables affected burrow presence and abundance. We found that the water table depth was a significant driver of burrow presence and abundance. Root biomass and vegetation cover were not significant drivers, although they did show up in the final models, explaining the data. These findings demonstrate empirical support for previous observations from other burrowing crayfish research and demonstrate the influence of fine-scale habitat when modeling elusive taxa requirements.

The Role of Prevotella Species in Female Genital Tract Infections.

Female genital tract infections (FGTIs) include vaginal infections (e.g., bacterial vaginosis [BV]), endometritis, pelvic inflammatory disease [PID], and chorioamnionitis [amniotic fluid infection]. They commonly occur in women of reproductive age and are strongly associated with multiple adverse health outcomes including increased risk of HIV/sexually transmitted infection acquisition and transmission, infertility, and adverse birth outcomes such as preterm birth. These FGTIs are characterized by a disruption of the cervicovaginal microbiota which largely affects host immunity through the loss of protective, lactic acid-producing Lactobacillus spp. and the overgrowth of facultative and strict anaerobic bacteria. Prevotella species (spp.), anaerobic Gram-negative rods, are implicated in the pathogenesis of multiple bacterial FGTIs. Specifically, P. bivia, P. amnii, and P. timonensis have unique virulence factors in this setting, including resistance to antibiotics commonly used in treatment. Additionally, evidence suggests that the presence of Prevotella spp. in untreated BV cases can lead to infections of the upper female genital tract by ascension into the uterus. This narrative review aims to explore the most common Prevotella spp. in FGTIs, highlight their important role in the pathogenesis of FGTIs, and propose future research in this area.

Deliberately introduced dung beetles in Australia: 12 years of occurrence and abundance records from 2001 to 2022.

Since 1968, the Australian Dung Beetle Project has carried out field releases of 43 deliberately introduced dung beetle species for the biological control of livestock dung and dung-breeding pests. Of these, 23 species are known to have become established. For most of these species, sufficient time has elapsed for population expansion to fill the extent of their potential geographic range through both natural and human-assisted dispersal. Consequently, over the last 20 years, extensive efforts have been made to quantify the current distribution of these introduced dung beetles, as well as the seasonal and spatial variation in their activity levels. Much of these data and their associated metadata have remained unpublished, and they have not previously been synthesized into a cohesive dataset. Here, we collate and report data from the three largest dung beetle monitoring projects from 2001 to 2022. Together, these projects encompass data collected from across Australia, and include records for all 23 species of established dung beetles introduced for biocontrol purposes. In total, these data include 22,718 presence records and 213,538 absence records collected during 10,272 sampling events at 546 locations. Most presence records (97%) include abundance data. In total, 1,752,807 dung beetles were identified as part of these data. The distributional occurrence and abundance data can be used to explore questions such as factors influencing dung beetle species distributions, dung beetle biocontrol, and insect-mediated ecosystem services. These data are provided under a CC-BY-NC 4.0 license and users are encouraged to cite this data paper when using the data.

Use of an Additional Updated 2023-2024 COVID-19 Vaccine Dose for Adults Aged ≥65 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2024.

COVID-19 remains an important public health threat, despite overall decreases in COVID-19-related severe disease since the start of the COVID-19 pandemic. COVID-19-associated hospitalization rates remain higher among adults aged ≥65 years relative to rates in younger adults, adolescents, and children; during October 2023-January 2024, 67% of all COVID-19-associated hospitalizations were among persons aged ≥65 years. On September 12, 2023, CDC's Advisory Committee on Immunization Practices (ACIP) recommended updated (2023-2024 Formula) COVID-19 vaccination with a monovalent XBB.1.5-derived vaccine for all persons aged ≥6 months to protect against severe COVID-19-associated illness and death. Because SARS-CoV-2 continues to circulate throughout the year, and because of the increased risk for COVID-19-related severe illness in persons aged ≥65 years, the protection afforded by updated vaccines against JN.1 and other currently circulating variants, and the expected waning of vaccine-conferred protection against disease, on February 28, 2024, ACIP recommended all persons aged ≥65 years receive 1 additional dose of the updated (2023-2024 Formula) COVID-19 vaccine. Implementation of these recommendations is expected to enhance immunity that might have waned and decrease the risk for severe COVID-19-associated outcomes, including death, among persons aged ≥65 years.

Gut Microbial Dysbiosis Differs in Two Distinct Cachectic Tumor-Bearing Models Consuming the Same Diet.

The impact of cancer cachexia on the colonic microbiota is poorly characterized. This study assessed the effect of two cachectic-producing tumor types on the gut microbiota to determine if a similar dysbiosis could be found. In addition, it was determined if a diet containing an immunonutrient-rich food (walnuts) known to promote the growth of probiotic bacteria in the colon could alter the dysbiosis and slow cachexia. Male Fisher 344 rats were randomly assigned to a semi-purified diet with or without walnuts. Then, within each diet group, rats were further assigned randomly to a treatment group: tumor-bearing ad libitum fed (TB), non-tumor-bearing ad libitum fed (NTB-AL), and non-tumor-bearing group pair-fed to the TB (NTB-PF). The TB group was implanted either with the Ward colon carcinoma or MCA-induced sarcoma, both transplantable tumor lines. Fecal samples were collected after the development of cachexia, and bacteria species were identified using 16S rRNA gene analysis. Both TB groups developed cachexia but had a differently altered gut microbiome. Beta diversity was unaffected by treatment (NTB-AL, TB, and NTB-PF) regardless of tumor type but was affected by diet. Also, diet consistently changed the relative abundance of several bacteria taxa, while treatment and tumor type did not. The control diet increased the abundance of A. Anaeroplasma, while the walnut diet increased the genus Ruminococcus. There were no common fecal bacterial changes characteristic of cachexia found. Diet consistently changed the gut microbiota, but these changes were insufficient to slow the progression of cachexia, suggesting cancer cachexia is more complex than a few gut microbiota shifts.

A Study on Auto-Catalysis and Product Inhibition: A Nucleophilic Aromatic Substitution Reaction Catalysed within the Cavity of an Octanuclear Coordination Cage.

The ability of an octanuclear cubic coordination cage to catalyse a nucleophilic aromatic substitution reaction on a cavity-bound guest was studied with 2,4-dinitrofluorobenzene (DNFB) as the guest/substrate. It was found that DNFB undergoes a catalysed reaction with hydroxide ions within the cavity of the cubic cage (in aqueous buffer solution, pH 8.6). The rate enhancement of kcat/kuncat was determined to be 22, with cavity binding of the guest being required for catalysis to occur. The product, 2,4-dinitrophenolate (DNP), remained bound within the cavity due to electrostatic stabilisation and exerts two apparently contradictory effects: it initially auto-catalyses the reaction when present at low concentrations, but at higher concentrations inhibits catalysis when a pair of DNP guests block the cavity. When encapsulated, the UV/Vis absorption spectrum of DNP is red-shifted when compared to the spectrum of free DNP in aqueous solution. Further investigations using other aromatic guests determined that a similar red-shift on cavity binding also occurred for 4-nitrophenolate (4NP) at pH 8.6. The red-shift was used to determine the stoichiometry of guest binding of DNP and 4NP within the cage cavity, which was confirmed by structural analysis with X-ray crystallography; and was also used to perform catalytic kinetic studies in the solution-state.

Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort.

BACKGROUND: Individuals with rare kidney diseases account for 5-10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. METHODS: People aged 0-96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan-Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m2 or more to first eGFR of less than 30 mL/min per 1·73 m2 (the therapeutic trial window). FINDINGS: Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9-16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0·0001), but better survival rates (standardised mortality ratio 0·42 [95% CI 0·32-0·52]; p<0·0001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. INTERPRETATION: Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3-5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. FUNDING: RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity.

Dermal absorption of high molecular weight parent and alkylated polycyclic aromatic hydrocarbons from manufactured gas plant soils using in vitro assessment.

An enhanced in vitro human dermal bioavailability method was developed to measure the release of twenty parent and seven alkylated high molecular weight (HMW) polycyclic aromatic hydrocarbons (PAHs) from contaminated soils collected from five former manufactured Gas Plants (MGP) in England. GC-MS/MS was used to quantify HMW PAHs in soil, Strat-M artificial membrane representing skin, and synthetic receptor solution (RS) representing systemic circulation at 1-h, 10-h, and 24-h timesteps. Fluoranthene and pyrene exhibited the highest fluxes from soils to membrane (ranging from 9.5 - 281 ng/cm2/h) and soil to RS (

Standard rodent diets differentially impact alcohol consumption and preference and gut microbiome diversity.

Alcohol Use Disorder (AUD) is a complex and widespread disease with limited pharmacotherapies. Preclinical animal models of AUD use a variety of voluntary alcohol consumption procedures to recapitulate different phases of AUD including binge alcohol consumption and dependence. However, voluntary alcohol consumption in mice is widely variable rendering it difficult to reproduce results across labs. Accumulating evidence indicates that different brands of commercially available rodent chow can profoundly influence alcohol intake. In this study, we investigated the effects of three commercially available and widely used rodent diet formulations on alcohol consumption and preference in C57BL/6J mice using the 24h intermittent access procedure. The three brands of chow tested were LabDiet 5001 (LD 5001), LabDiet 5053 (LD 5053), and Teklad 2019S (TL2019S) from two companies (Research Diets and Envigo respectively). Mice fed LD5001 displayed the highest levels of alcohol consumption and preference followed by LD5053 and TL2019S. We also found that alcohol consumption and preference could be rapidly switched by changing the diet 48h prior to alcohol administration. Sucrose, saccharin, and quinine preference were not altered suggesting that the diets did not alter taste perception. We also found that mice fed LD5001 displayed increased quinine-resistant alcohol intake compared to mice fed TL2019S, suggesting that diets could influence the development of "compulsive" like alcohol consumption. We profiled the gut microbiome of water and alcohol drinking mice that were maintained on different diets and found significant differences in bacterial alpha and beta diversity, which could impact gut-brain axis signaling and alcohol consumption.

Microbial interactions among Gardnerella, Prevotella and Fannyhessea prior to incident bacterial vaginosis: protocol for a prospective, observational study.

INTRODUCTION: The aetiology of bacterial vaginosis (BV), a biofilm-associated vaginal infection, remains unknown. Epidemiologic data suggest that it is sexually transmitted. BV is characterised by loss of lactic acid-producing lactobacilli and an increase in facultative and strict anaerobic bacteria. Gardnerella spp are present in 95%-100% of cases; Gardnerella vaginalis has been found to be more virulent than other BV-associated bacteria (BVAB) in vitro. However, G. vaginalis is found in women with normal vaginal microbiota and colonisation is not sufficient for BV development. We hypothesise that Gardnerella spp initiate BV biofilm formation, but incident BV (iBV) requires incorporation of other key BVAB (ie, Prevotella bivia, Fannyhessea vaginae) into the biofilm that alter the transcriptome of the polymicrobial consortium. This study will investigate the sequence of microbiologic events preceding iBV. METHODS AND ANALYSIS: This study will enrol 150 women aged 18-45 years with normal vaginal microbiota and no sexually transmitted infections at a sexual health research clinic in Birmingham, Alabama. Women will self-collect twice daily vaginal specimens up to 60 days. A combination of 16S rRNA gene sequencing, qPCR for Gardnerella spp, P. bivia and F. vaginae, and broad range 16S rRNA gene qPCR will be performed on twice daily vaginal specimens from women with iBV (Nugent score 7-10 on at least 2 consecutive days) and controls (with comparable age, race, contraceptive method and menstrual cycle days) maintaining normal vaginal microbiota to investigate changes in the vaginal microbiota over time for women with iBV. Participants will complete daily diaries on multiple factors including sexual activity. ETHICS AND DISSEMINATION: This protocol is approved by the University of Alabama at Birmingham Institutional Review Board (IRB-300004547) and written informed consent will be obtained from all participants. Findings will be presented at scientific conferences and published in peer-reviewed journals as well as disseminated to providers and patients in communities of interest.

Chikungunya seroprevalence, force of infection, and prevalence of chronic disability after infection in endemic and epidemic settings: a systematic review, meta-analysis, and modelling study.

BACKGROUND: Chikungunya is an arboviral disease transmitted by Aedes aegypti and Aedes albopictus mosquitoes with a growing global burden linked to climate change and globalisation. We aimed to estimate chikungunya seroprevalence, force of infection (FOI), and prevalence of related chronic disability and hospital admissions in endemic and epidemic settings. METHODS: In this systematic review, meta-analysis, and modelling study, we searched PubMed, Ovid, and Web of Science for articles published from database inception until Sept 26, 2022, for prospective and retrospective cross-sectional studies that addressed serological chikungunya virus infection in any geographical region, age group, and population subgroup and for longitudinal prospective and retrospective cohort studies with data on chronic chikungunya or hospital admissions in people with chikungunya. We did a systematic review of studies on chikungunya seroprevalence and fitted catalytic models to each survey to estimate location-specific FOI (ie, the rate at which susceptible individuals acquire chikungunya infection). We performed a meta-analysis to estimate the proportion of symptomatic patients with laboratory-confirmed chikungunya who had chronic chikungunya or were admitted to hospital following infection. We used a random-effects model to assess the relationship between chronic sequelae and follow-up length using linear regression. The systematic review protocol is registered online on PROSPERO, CRD42022363102. FINDINGS: We identified 60 studies with data on seroprevalence and chronic chikungunya symptoms done across 76 locations in 38 countries, and classified 17 (22%) of 76 locations as endemic settings and 59 (78%) as epidemic settings. The global long-term median annual FOI was 0·007 (95% uncertainty interval [UI] 0·003-0·010) and varied from 0·0001 (0·00004-0·0002) to 0·113 (0·07-0·20). The highest estimated median seroprevalence at age 10 years was in south Asia (8·0% [95% UI 6·5-9·6]), followed by Latin America and the Caribbean (7·8% [4·9-14·6]), whereas median seroprevalence was lowest in the Middle East (1·0% [0·5-1·9]). We estimated that 51% (95% CI 45-58) of people with laboratory-confirmed symptomatic chikungunya had chronic disability after infection and 4% (3-5) were admitted to hospital following infection. INTERPRETATION: We inferred subnational heterogeneity in long-term average annual FOI and transmission dynamics and identified both endemic and epidemic settings across different countries. Brazil, Ethiopia, Malaysia, and India included both endemic and epidemic settings. Long-term average annual FOI was higher in epidemic settings than endemic settings. However, long-term cumulative incidence of chikungunya can be similar between large outbreaks in epidemic settings with a high FOI and endemic settings with a relatively low FOI. FUNDING: International Vaccine Institute.

Probiotic Limosilactobacillus reuteri DSM 17938 Changes Foxp3 Deficiency-Induced Dyslipidemia and Chronic Hepatitis in Mice.

The probiotic Limosilactobacillus reuteri DSM 17938 produces anti-inflammatory effects in scurfy (SF) mice, a model characterized by immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (called IPEX syndrome in humans), caused by regulatory T cell (Treg) deficiency and is due to a Foxp3 gene mutation. Considering the pivotal role of lipids in autoimmune inflammatory processes, we investigated alterations in the relative abundance of lipid profiles in SF mice (± treatment with DSM 17938) compared to normal WT mice. We also examined the correlation between plasma lipids and gut microbiota and circulating inflammatory markers. We noted a significant upregulation of plasma lipids associated with autoimmune disease in SF mice, many of which were downregulated by DSM 17938. The upregulated lipids in SF mice demonstrated a significant correlation with gut bacteria known to be implicated in the pathogenesis of various autoimmune diseases. Chronic hepatitis in SF livers responded to DSM 17938 treatment with a reduction in hepatic inflammation. Altered gene expression associated with lipid metabolism and the positive correlation between lipids and inflammatory cytokines together suggest that autoimmunity leads to dyslipidemia with impaired fatty acid oxidation in SF mice. Probiotics are presumed to contribute to the reduction of lipids by reducing inflammatory pathways.

Parental preconception stress in zebrafish induces long-lasting anxiety in offspring.

The growth and function of the vertebrate brain are impacted by environmental stimuli and early life stress. Adults who experience chronic stress during early life are more likely to suffer various neurodevelopmental and health issues. However, our understanding of how these specific environmental signals at different developmental stages affect brain development is poorly understood. In this study, we investigated if stress in parents prior to conception modulates neurodevelopment in offspring. We used a chronic unpredictable stress model adapted to zebrafish, which is an increasingly popular vertebrate model in neuroscience research to investigate the effects of both maternal and paternal preconception stress on offspring behavior. We evaluated the responsiveness of three anxiety-related behavioral paradigms in zebrafish: the novel tank test, thigmotaxis, and shoaling behavior. We found larvae from stressed females exhibited anxiety-like behavior in a thigmotaxis assay. As these larvae matured into adults, they continued to exhibit anxiety-like behavior in a novel tank and shoaling behavioral assay. These studies indicate preconception stress exposure in parents can induce life-long alterations in offspring neurodevelopment. Further, these results expand the hypothesis that chronically elevated glucocorticoid signaling not only in stressed mothers, but also stressed dads can affect neurodevelopment in offspring. We propose that zebrafish may be a useful model to study the transgenerational effects of chronic stress mediated via the maternal and paternal line.

The melon Fom-1-Prv resistance gene pair: Correlated spatial expression and interaction with a viral protein.

The head-to-head oriented pair of melon resistance genes, Fom-1 and Prv, control resistance to Fusarium oxysporum races 0 and 2 and papaya ringspot virus (PRSV), respectively. They encode, via several RNA splice variants, TIR-NBS-LRR proteins, and Prv has a C-terminal extra domain with a second NBS homologous sequence. In other systems, paired R-proteins were shown to operate by "labor division," with one protein having an extra integrated domain that directly binds the pathogen's Avr factor, and the second protein executing the defense response. We report that the expression of the two genes in two pairs of near-isogenic lines was higher in the resistant isoline and inducible by F. oxysporum race 2 but not by PRSV. The intergenic DNA region separating the coding sequences of the two genes acted as a bi-directional promoter and drove GUS expression in transgenic melon roots and transgenic tobacco plants. Expression of both genes was strong in melon root tips, around the root vascular cylinder, and the phloem and xylem parenchyma of tobacco stems and petioles. The pattern of GUS expression suggests coordinated expression of the two genes. In agreement with the above model, Prv's extra domain was shown to interact with the cylindrical inclusion protein of PRSV both in yeast cells and in planta.