Significant Population Differences Research Articles

Combined maternal and post-weaning high fat diet inhibits male offspring's prostate cancer tumorigenesis in transgenic adenocarcinoma of mouse prostate model.

High fat diet (HFD) and its responsive change of gut microbiota are associated with numerous diseases in human and animal studies. But how maternal and post-weaning HFD may influence the tumorigenesis of prostate cancer (PCa) in male offspring has not yet been reported. We studied both solitary and combined effects of maternal or/and post-weaning HFD on the tumorigenesis of prostate in offspring using a transgenic adenocarcinoma of mouse prostate (TRAMP) model. TRAMP male mice (n = 24) were born to and fostered onto control diet or HFD-fed mothers, the weaned pups were further fed control or fat diet. All mice were sacrificed at the 28th week. The prostate histopathology was performed. The gut microbiota was analyzed by fecal 16S rRNA pyrosequencing, and the serum metabolites were determined by LC-MS/MS. Our results indicated that post-weaning HFD could significantly promote the PCa tumorigenesis in offspring (P = 0.031), and similar results were found in maternal HFD group but with no significant differences (P = 0.056). However, combined maternal and post-weaning HFD could significantly reduce the PCa tumorigenesis in offspring (P = 0.019). Significant differences in specific microbial populations and serum metabolites were observed across groups. For example, mice with combined maternal and post-weaning HFD had higher abundance of gut Lachonospiraceae, Roseburia, and Amycolatopsis, increased serum L-methionine (P = 0.0052), and decreased serum α-linolenic acid (P < 0.001). This study highlights the inhibitory effects of combined maternal and post-weaning HFD on PCa tumorigenesis, and provides new insights into the interactions between diet, gut microbiota, serum metabolites, and PCa.

High Microbial Diversity Despite Extremely Low Biomass in a Deep Karst Aquifer

Despite the importance of karst aquifers as a source of drinking water, little is known about the role of microorganisms in maintaining the quality of this water. One of the limitations in exploring the microbiology of these environments is access, which is usually limited to wells and surface springs. In this study, we compared the microbiology of the Madison karst aquifer sampled via the potentiometric lakes of Wind Cave with surface sampling wells and a spring. Our data indicated that only the Streeter Well (STR), which is drilled into the same hydrogeologic domain as the Wind Cave Lakes (WCL), allowed access to water with the same low biomass (1.56–9.25 × 103 cells mL-1). Filtration of ∼300 L of water from both of these sites through a 0.2 μm filter allowed the collection of sufficient cells for DNA extraction, PCR amplification of 16S rRNA gene sequences, and identification through pyrosequencing. The results indicated that bacteria (with limited archaea and no detectable eukaryotic organisms) dominated both water samples; however, there were significant taxonomic differences in the bacterial populations of the samples. The STR sample was dominated by a single phylotype within the Gammaproteobacteria (Order Acidithiobacillales), which dramatically reduced the overall diversity and species richness of the population. In WCL, despite less organic carbon, the bacterial population was significantly more diverse, including significant contributions from the Gammaproteobacteria, Firmicutes, Chloroflexi, Actinobacteria, Planctomycetes, Fusobacter, and Omnitrophica phyla. Comparisons with similar oligotrophic environments suggest that karst aquifers have a greater species richness than comparable surface environs. These data also demonstrate that Wind Cave provides a unique opportunity to sample a deep, subterranean aquifer directly, and that the microbiology of such aquifers may be more complex than previously anticipated.

First Insights into the Gut Microbiota of Mexican Patients with Celiac Disease and Non-Celiac Gluten Sensitivity.

Gluten-related disorders (GRDs) are common chronic enteropathies and increasing evidence suggests an involvement of the gut microbiota. We examined the gut microbiota in Mexican people afflicted with GRDs. Ultra-high-throughput 16S marker sequencing was used to deeply describe the duodenal and fecal microbiota of patients with celiac disease (CD, n = 6), non-celiac gluten sensitivity (NCGS, n = 12), and healthy subjects (n = 12) from our local area. Additionally, we also investigated the changes in gut microbiota after four weeks on a gluten-free diet (GFD) in a subset of patients from whom paired samples were available. Despite a high inter-individual variability, significant differences in various microbial populations were identified. The linear discriminant analysis (LDA) effect size (LEfSe) method revealed that the genus Actinobacillus and the family Ruminococcaceae were higher in the duodenal and fecal microbiota of NCGS patients, respectively, while Novispirillum was higher in the duodenum of CD patients (p < 0.05, LDA score > 3.5). Interestingly, paired samples from NCGS patients showed a significant difference in duodenal Pseudomonas between the baseline period (median: 1.3%; min/max: 0.47–6.8%) and the period after four weeks on GFD (14.8%; 2.3–38.5%, p < 0.01, Wilcoxon signed-rank test). These results encourage more research on GRDs in México.

Overexpressing ovotransferrin and avian β-defensin-3 improves antimicrobial capacity of chickens and poultry products.

Zoonotic and foodborne diseases pose a significant burden, decreasing both human and animal health. Modifying chickens to overexpress antimicrobials has the potential to decrease bacterial growth on poultry products and boost chicken innate immunity. Chickens overexpressing either ovotransferrin or avian β-defensin-3 (AvβD3) were generated using Tol-2 transposons. Transgene expression at the RNA and protein level was seen in egg white, breast muscle, and serum. There were significant differences in the immune cell populations in the blood, bursa, and spleen associated with transgene expression including an increased proportion of CD8+ cells in the blood of ovotransferrin and AvβD3 transgenic birds. Expression of the antimicrobials inhibited the in vitro growth of human and chicken bacterial pathogens and spoilage bacteria. For example, transgene expression significantly reduced growth of aerobic and coliform bacteria in breast muscle and decreased the growth of Salmonella enterica in egg white. Overall these results indicate that overexpression of antimicrobials in the chicken can impact the immune system and increase the antimicrobial capacity of poultry products.

Characteristics of pathogenic bacteria isolates associated with the gut and gill of molluscan shellfish, Eastern Cape, South Africa

Introduction: Infectious diseases attributable to the consumption of raw and lightly cooked molluscan shellfish are caused by bacterial agents that are associated either with human waste disposed into the ocean or those of marine origin. This has led to the increase in prevalence of bacterial diseases and microbial resistance to antibiotics.&#x0D; Method: Samples of P. perna were dissected and homogenized for bacterial isolation. Six bacteria were isolated, identified and evaluated for their antimicrobial susceptibility profiling.&#x0D; Results: The microbial counts obtained revealed significant differences in the pathogenic bacteria populations found in the gut and gill of Perna perna. The morphological characteristics of the isolates were found to be of different shapes. All the isolates were catalase and oxidase positive except Vibrio spp. which was negative to the latter. Chloramphenicol and ciprofloxacillin were the most effective antibiotics against all the isolates, each exhibiting 100% efficacy. The highest resistance to ampicilin was observed in Salmonella spp., Shigella spp., Listeria monocytogenes and Staphylococcus xylosus.&#x0D; Conclusions: The results revealed that marine habitats are reservoirs of bacterial pathogens and there is increased resistance to antibiotic therapy, thereby constituting risks to public health. Therefore, appropriate surveillance measures to safeguard the health of shellfish consumers’ should be established.

The Epidemiology of Hepatitis D Virus in North Africa: A Systematic Review and Meta-Analysis.

Background Hepatitis D virus (HDV) infection has been considered a serious neglected pandemic, particularly in developing countries. The virus causes a more severe disease than mono infection with hepatitis B virus (HBV). The epidemiology of HDV is not well documented in North Africa, which is known to be endemic for HBV. In this study, we explored the prevalence of HDV infection and also attempted to identify factors associated with hepatitis D positive status among chronic hepatitis B patients in North Africa. Methods The electronic databases PubMed, Embase, Scopus, Science Direct, Web of Science, and Google Scholar were comprehensively searched for all papers published between January 1, 1998, and December 31, 2017, using appropriate strategies containing all related keywords, including North Africa, names of countries in the region, and all permutations of hepatitis D virus. The estimated prevalence of HDV in North Africa was calculated as an average of the pooled infection prevalence in each country weighted by the ratio of the country's hepatitis D virus population to the study's sample size in the survey data analysis. Findings A total of 312 studies were identified and 32 were included in this study, with a total sample of 4907 individuals screened for HDV. There was considerable variability in the prevalence estimates of HDV within the countries of the region. The overall prevalence of HDV in the general population of North Africa was 5·01% (95% CI: 1·25–8·27) and in liver disease patients it was 20.7% (95% CI:9.87–44.53). Genotype-1 was the most prominent genotype reported in five published studies. Ten studies reported on HDV RNA in participants who were seropositive for HDV, and four studies highlighted the impact of demographic factors (sex and age). No study showed the impact of risk factors on the prevalence of HDV in North Africa. Interpretation This review provides a comprehensive assessment of the burden of HDV in Northern Africa. There were significant differences in seroprevalence, study population, and diagnostic testing between the countries in the region. The results presented here will alert health professionals to implement clear policies based on evidence to diminish the burden of HDV infection. Such measures may include but are not restricted to improving the laboratory diagnostic tests and initiating patient data registries and blood screening. Further epidemiological and research studies are needed to explore the risk factors, coinfections, and approaches to increase testing for HDV, particularly in high-risk subpopulations, such as intravenous drug users and immigrants, and to define the consequences of HDV infection in North Africa.

Infant Colic Represents Gut Inflammation and Dysbiosis

To dissect potential confounding effects of breast milk and formula feeding on crying + fussing, fecal calprotectin, and gut microbiota in babies with colic. We hypothesized that infant colic is associated with gut inflammation linked to intestinal dysbiosis. A nested case-control design of 3 of our studies was used to analyze clinical and laboratory data at presentation, comparing babies with colic with controls. All investigators other than the biostatistician were blinded during data analysis. Subjects were recruited based on their age and crying + fussy time. We screened 65 infants, 37 with colic, as defined by Barr diary (crying + fussing time >3 hours daily), who were compared with 28 noncolicky infants. Fecal calprotectin was elevated in babies with colic. For each mode of infant feeding (breast milk, formula, or breast + formula), infants' fecal calprotectin was higher in babies with colic. Infants with colic had similar levels of fecal alpha diversity (richness) when compared with controls, and alpha diversity was lower in breast-fed babies. Beta diversity at the phylum level revealed significant differences in microbial population. A phylum difference resulted from reduced Actinobacteria (95% of which are Bifidobacilli) in babies with colic. Species significantly associated with colic were Acinetobacter and Lactobacillus iners. Colic is linked with gut inflammation (as determined by fecal calprotectin) and dysbiosis, independent of mode of feeding, with fewer Bifidobacilli. Clinicaltrials.gov: NCT01279265 and NCT01849991.

Comparing the asthma control in overweight/obese and normal weight pediatric patients: A retrospective study in West Texas

Asthma is one of the most common chronic diseases in children. Excess weight is thought to contribute adversely to this disease and has been associated with both an increased incidence and severity of asthma in multiple studies. However, this information does not seem to be conclusive, since there are also studies showing either no relationship or a relationship only in certain subpopulations of children. The aim of this study was to see if we could identify any pattern in the relationship of weight and asthma severity and control in our pediatric population at a university affiliated clinic in rural West Texas. We were unable to find statistically significant differences either in the overall population or in the boys or girls subpopulations. We estimate based on our results that future studies would need at least 800 children to achieve adequate statistical power. More well designed studies are needed to clarify and confirm the relationship between obesity and asthma control and severity in children.

Clinical and Immunological Response to Sublingual Vaccination for the Prevention of Recurrent Urinary Tract Infections in Kidney Transplant Patients

Introduction Frequent antibiotic use in urinary tract infections (UTI) is associated with an elevated risk of adverse events as well as developing multidrug resistant UTI. Sublingual vaccination with Uromune® has been shown to reduce the frequency of UTI in patients suffering from recurrent urinary tract infections (rUTI) in the general population. The aim of this study was to describe the clinical and immunological response to this vaccine in kidney transplant recipients with rUTI. Material and Method Sublingual vaccination with Uromune® was prescribed to kidney transplant patients who met criteria for rUTI (≥2 UTI in the previous 6 months or ≥ 3 UTI in the previous year), administering 2 daily sublingual puffs for 6 months. Patients in the first post-transplant year were excluded. After 1 year of follow-up, the number of UTI episodes and severe episodes requiring hospital admittance were compared to those in the previous year. Changes in renal function and anti-HLA antibodies were measured. Humoral and cellular immune response were monitored by measuring clonal B and T-lymphocyte populations before vaccination and after 3 and 6 months of vaccination. Results 43 kidney transplant recipients with rUTI completed sublingual vaccination with Uromune® for 6 months, age 56.2±15.0 years, median transplant duration 6.0 years (interquartile range (IQR) 3.7-10.5), 86% females, 32.6% had polycystic kidney disease, 32.6% diagnosed with diabetes mellitus, 39.5% had urinary tract structural or functional abnormalities. The mean incidence of UTI decreased from 4.2 to 2.7 episodes per year (CI 95% 0.9-2.2, p<0,001). After one year, 16.3% of patients were completely free from UTI and 46.5% had fewer infections. After 6 months from vaccination, there was an increase in total B lymphocytes from 6.9% (IQR 3.2-13.6) to 8% (IQR 4.4-15.6)(p=0.012), and in memory B cells from 34.3% (IQR 14.1-48.8) to 40.7% (IQR 30.8-54)(p=0.002). There was a decrease in transitional B lymphocytes from 4.7% (IQR 2-9.7) to 1.1% (IQR 0.3-2.5)(p<0.001), in switched memory B cells from 29.6% (IQR 15.6-45) to 14.6% (IQR 7.6-29.3)(p=0.038), and in plasmablasts from 8.6% (IQR 2.1-31.4) to 1.2% (IQR 0.5-3.4)(p=0.009). In vaccine responders, total B lymphocytes increased from 8.6% (IQR 3.7-15.5) to 11.6% (IQR 5.3-16.7)(p=0.005), while plasmablasts decreased from 13% (IQR 2.4-33.1) to 0.75% (IQR 0.3-2.1)(p=0.028) and switched memory B cells from 19.6% (7.3-44.6) to 13.9% (7.2-18). These changes were not found in vaccine non-responders. There were no significant differences in clonal T-cell populations between both groups. No significant changes in serum creatinine or development of new anti-HLA antibodies were found. Conclusions Sublingual administration of polybacterial vaccine Uromune® can reduce the frequency of UTI in kidney transplant patients with rUTI through the induction of humoral immune response. In our study, no changes in renal function or development of new anti-HLA antibodies were found.

Population structure, behavior, and distribution pattern of the river lapwing Vanellus duvaucelii (Lesson, 1826)

A field study was carried out to investigate the population status, behavior, and distribution pattern of river lapwings during the study period of 2015–2017 in the Raebareli district, Uttar Pradesh, India. There was a significant difference in the mean population of river lapwings along the study sites but less significant difference in the mean population seasonally. An average of 541 individuals of river lapwings have been reported during the study period. The mean population size was maximum (164.5 ± 28.67) at Gegaso in 2016 and minimum (56.25 ± 28.34) at Sultanpur Barhaia in 2017, whereas the seasonal population status showed maximum (199.5 ± 2.12) count in the summer season at Gegaso and minimum (52.0 ± 4.2) in winter at Sultanpur Barhaia. Moreover, maximum (n = 38) nesting pairs were estimated at Gegaso and least (n = 11) at Unchahar. There was less significant difference in the number of chicks counted in both the breeding seasons (2016 and 2017), but significantly a higher number of chicks (n = 86) were documented at Gegaso and least (n = 25) at Sultanpur Barhaia. Overall, there was no significant difference in the behavioral activities during the breeding and nonbreeding season. The present study clearly indicates that the river bank was the most preferred habitat type and that the distribution pattern was found to be clumped in river lapwings.

Mutation induction as a strategy to overcome the restricted genetic base in Physalis

Abstract The restricted genetic base in physalis in Southern Brazil is a challenge that requires genetic breeding for the achievement of fruits with superior agronomic quality. Therefore, genetic changes were induced in physalis for the selection of populations with superior fruit quality. To that end, seven populations of physalis were submitted to gamma irradiation (0,100 and 200 Grays – Gy), which provided 21 populations. Significant population difference was observed, which indicates the existence of variability between at least two populations of physalis. The contrasts showed difference for Colômbia01, Colômbia02, Caçador and CAV. The mutation induction was effective at causing genetic variations in these populations. For Colombia01 (100 Gy), it was observed reduction of 3.97 mm and 2.56 mm (200 Gy) in the transverse fruit diameter (DTF). In the Colombia02 population (200 Gy), there was an increase of 2.99 mm in the longitudinal fruit diameter (DLT) and 4.90 mm in the DTF. For CAV (200 Gy), it was found the increase of 1.81 ºBrix. Mutation induction was beneficial in these cases, but fruit quality is still below the potential of the crop, when compared to fruits from Andean countries. It is possible to suggest that quantitative traits, such as fruit mass (MF) and total soluble solids (SST), and the degree of ploidy in physalis (2n = 4x = 48) reduce the mutagenic agent ability to cause variations.

Association between the XPG gene rs2094258 polymorphism and risk of gastric cancer.

Xeroderma pigmentosum group G (XPG) plays an important role in maintaining the stability and integrity of genomic DNA. Previous studies demonstrate some XPG gene polymorphisms are associated with susceptibility to gastric cancer (GC). The association between XPG rs2094258 polymorphism and GC risk was investigated first by a hospital-based case-control study involving 386 patients and 439 controls and then by a meta-analysis. The polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLR). Xeroderma pigmentosum group G rs2094258 polymorphism was associated with an increased risk of GC in a Chinese population. The meta-analysis did not reveal any significant difference in the overall population. Subgroup analysis of geographic locations showed a significant association between the XPG gene rs2094258 polymorphism and GC risk in Southern China. Stratification analysis further indicated significant associations in hospital-based studies and studies using PCR-RFLR. Xeroderma pigmentosum group G gene rs2094258 polymorphism may be associated with an increased risk of GC in Southern China. Nevertheless, the findings of this meta-analysis should be validated by well-designed large-scale case-control studies among other ethnicities.

Comparison of the body size and age structure of Lebanon lizard, Phoenicolacerta laevis (Gray, 1838) at different altitudes in Turkey

In this study, comparison of a life history traits (e.g. body size, age at maturity, longevity) of two populations of Phoenicolacerta laevis from different altitudes is being carried out (Anamur, 22 m a.s.l.; Andırın, 1.083 m a.s.l.) for the first time. We applied phalangeal skeletochronology to obtain the age of juveniles and adults. Age was determined by counting the lines of arrested growth (LAGs) in cross-sections. Males in both populations were the larger of the two sexes and a male biased sexual dimorphism was determined for both populations. Body size (SVL) was similar in both sexes and populations. Age of maturity was calculated to be 3 years of age for males and females in both populations. The average age of males and females was calculated as 6.62 ± 0.37 (Mean±SE) and 6.11 ± 0.26 years in Anamur, and 6.15 ± 0.51 and 5.26 ± 0.24 years in Andırın. There was statistically significant variation between sexes, but no significant difference in populations was found in relation to age. For both populations, a significant positive correlation was found between age and SVL in males and females.

Growth parameters of autumn rice under various irrigation schedules and nutrient management

A field experiment was conducted at Instructional-cum-Research (ICR) Farm, Assam Agricultural University, Jorhat-13 during autumn season of 2015 to study the nutrient management of direct seeded autumn rice under various irrigation schedules. The experiment consisted of four irrigation schedules viz., I1(No irrigation), I2(Irrigation at tiller initiation (TI) + boot leaf stage (BL)), I3(Irrigation at TI + panicle initiation (PI) + BL), I4 (Irrigation at TI + PI + Grain filling stage(GF)) and three nutrient management practices viz.,F1(100 % RDF +2t/ha FYM), F2(50 % RDF +1.5 t/ha enriched compost), F3(50 % RDF + 1.5 t/ha Vermicompost). The trial was laid out in split plot design with three replications. The soil was sandy loam. Inglongkiri rice variety was used in the experiment. Results revealed that irrigation schedule I3(Irrigation at TI + PI + BL) recorded significantly the highest growth characters of rice in terms of plant height, number of leaves per plant, and dry matter accumulation. Different nutrient management practices brought about significant differences in plant population per and dry matter accumulation. The highest of these parameters were recorded under application of 50% RDF along with 1.5 t/ha enriched compost and this was statically at par with F1 (100% RDF +2 t/ha FYM).

Abdominal subcutaneous and visceral adipocyte size, lipolysis and inflammation relate to insulin resistance in male obese humans

Obesity is associated with a disturbed adipose tissue (AT) function characterized by adipocyte hypertrophy, an impaired lipolysis and pro-inflammatory phenotype, which contributes to insulin resistance (IR). We investigated whether AT phenotype in different AT depots of obese individuals with and without type 2 diabetes mellitus (T2DM) is associated with whole-body IR. Subcutaneous (SC) and visceral (V) AT biopsies from 18 lean, 17 obese and 8 obese T2DM men were collected. AT phenotype was characterized by ex vivo measurement of basal and stimulated lipolysis (mature adipocytes), adipocyte size distribution (AT tissue sections) and AT immune cells (flow cytometry). In VAT, mean adipocyte size, CD45+ leukocytes and M1 macrophages were significantly increased in both obese groups compared to lean individuals. In SCAT, despite adipocyte hypertrophy, no significant differences in immune cell populations between groups were found. In SCAT, multiple linear regression analysis showed that none of the AT phenotype markers independently contributed to HOMA-IR while in VAT, mean adipocyte size was significantly related to HOMA-IR. In conclusion, beside adipocyte hypertrophy in VAT, M1 macrophage- or B-cell-mediated inflammation, may contribute to IR, while inflammation in hypertrophic SCAT does not seem to play a major role in IR.

The association between gut microbiome, sex, age and body condition scores of horses in Maiduguri and its environs

The equine gut harbours complex microbial populations which influence physiology, metabolism, nutrition and immune functions, while disruption to the gut microbiota has been linked with conditions such as lameness, diabetes and obesity. Therefore, the present study was conducted to determine the association between microbial dysbiosis, sex, age and body condition scores (BCS) of horses (Equus equus caballus) in Maiduguri and its environs. Forty horses were assessed by convenient sampling, while faecal samples were collected and analyzed to determine the microbiomes in the various age groups with variable BSC in stallions and mares. The present study revealed that there was strong and not significant association between the microbial populations in the gut of horses and the various age groups (Chi-Squared test = 11.809; df = 18; P = 0.8570). There were significant (p < 0.0001) differences in the microbiome population in the guts of the horses. There were significant (p < 0.05) differences in the microbiomes in the various body scores. There were significant (P < 0.047) differences in the microbiomes of the mares and stallions. E. coli had the highest burden of microbial populations with 30.38*103 ± 1.04*103 in the guts of horses in the study area, while statistically there were no differences in the populations of Corynebacterium, Klebsiella, Salmonella, Staphylococcus and Streptococcus in the gut of horses in the study area relative to E. coli. This study provides information on the nature of bacterial population present in horses in Maiduguri and its Environs. Therefore, further high-throughput characterization of the faecal bacteria microbiome of horses is essential to enable comparison to disease state and thus develop diagnostic tests, prophylactic measures and appropriate treatments.

Prolonged cenicriviroc therapy reduces hepatic fibrosis despite steatohepatitis in a diet-induced mouse model of nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is a progressive liver disease projected to become the leading cause of cirrhosis and liver transplantation in the next decade. Cenicriviroc (CVC), a dual chemokine receptor 2 and 5 antagonist, prevents macrophage trafficking and is under clinical investigation for the treatment of human NASH fibrosis. We assessed the efficacy and durability of short and prolonged CVC therapy in a diet‐induced mouse model of NASH, the choline deficient, L‐amino acid‐defined, high‐fat diet (CDAHFD) model. C57BL/6 mice received 4 or 14 weeks of standard chow or the CDAHFD. CVC (10 mg/kg/day and 30 mg/kg/day for 4 weeks and 20 mg/kg/day and 30 mg/kg/day for 14 weeks) was initiated simultaneously with the CDAHFD. At 4 and 14 weeks, livers were harvested for histology and flow cytometric analyses of intrahepatic immune cells. High‐dose CVC (30 mg/kg/day) therapy in CDAHFD mice for 4 or 14 weeks inhibited intrahepatic accumulation of Ly6Chigh bone marrow‐derived macrophages. Prolonged CVC therapy (14 weeks) yielded no significant differences in the total intrahepatic macrophage populations among treatment groups but increased the frequency of intrahepatic anti‐inflammatory macrophages in the high‐dose CVC group. Despite ongoing steatohepatitis, there was significantly less fibrosis in CDAHFD mice receiving high‐dose CVC for 14 weeks based on histologic and molecular markers, mirroring observations in human NASH CVC trials. CVC also directly inhibited the profibrotic gene signature of transforming growth factor‐β‐stimulated primary mouse hepatic stellate cells in vitro. Conclusion: CVC is a novel therapeutic agent that is associated with reduced fibrosis despite ongoing steatohepatitis. Its ability to alter intrahepatic macrophage populations and inhibit profibrogenic genes in hepatic stellate cells in NASH livers may contribute to its observed antifibrotic effect. (Hepatology Communications 2018;2:529‐545)

Population-dependent Intron Retention and DNA Methylation in Breast Cancer.

Regulation of gene expression by DNA methylation in gene promoter regions is well studied; however, the effects of methylation in the gene body (exons and introns) on gene expression are comparatively understudied. Recently, hypermethylation has been implicated in the inclusion of alternatively spliced exons; moreover, exon recognition can be enhanced by recruiting the methyl-CpG-binding protein (MeCP2) to hypermethylated sites. This study examines whether the methylation status of an intron is correlated with how frequently the intron is retained during splicing using DNA methylation and RNA sequencing data from breast cancer tissue specimens in The Cancer Genome Atlas. Interestingly, hypomethylation of introns is correlated with higher levels of intron expression in mRNA and the methylation level of an intron is inversely correlated with its retention in mRNA from the gene in which it is located. Furthermore, significant population differences were observed in the methylation level of retained introns. In African-American donors, retained introns were not only less methylated compared to European-American donors, but also were more highly expressed. This underscores the need for understanding epigenetic differences in populations and their correlation with breast cancer is an important step toward achieving personalized cancer care.Implications: This research contributes to the understanding of how epigenetic markers in the gene body communicate with the transcriptional machinery to control transcript diversity and differential biological response to changes in methylation status could underlie some of the known, yet unexplained, disparities in certain breast cancer patient populations. Mol Cancer Res; 16(3); 461-9. ©2018 AACR.

Cortical Thinning and Cognitive Impairment in Parkinson's Disease without Dementia.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized clinically by motor dysfunction (bradykinesia, rigidity, tremor, and postural instability), and pathologically by the loss of dopaminergic neurons in the substantia nigra of the basal ganglia. Growing literature supports that cognitive deficits may also be present in PD, even in non-demented patients. Gray matter (GM) atrophy has been reported in PD and may be related to cognitive decline. This study investigated cortical thickness in non-demented PD subjects and elucidated its relationship to cognitive impairment using high-resolution T1-weighted brain MRI and comprehensive cognitive function scores from 71 non-demented PD and 48 control subjects matched for age, gender, and education. Cortical thickness was compared between groups using a flexible hierarchical multivariate Bayesian model, which accounts for correlations between brain regions. Correlation analyses were performed among brain areas and cognitive domains as well, which showed significant group differences in the PD population. Compared to Controls, PD subjects demonstrated significant age-adjusted cortical thinning predominantly in inferior and superior parietal areas and extended to superior frontal, superior temporal, and precuneus areas (posterior probability >0.9). Cortical thinning was also found in the left precentral and lateral occipital, and right postcentral, middle frontal, and fusiform regions (posterior probability >0.9). PD patients showed significantly reduced cognitive performance in executive function, including set shifting (p = 0.005) and spontaneous flexibility (p = 0.02), which were associated with the above cortical thinning regions (p < 0.05).

Quasispecies variant of pre-S/S gene in HBV-related hepatocellular carcinoma with HBs antigen positive and occult infection

BackgroundHepatocellular carcinoma (HCC) can develop in patients who are negative for the hepatitis B surface antigen (HBsAg) in serum but positive for hepatitis B virus (HBV) DNA in the liver, referred to as occult HBV infection (OBI). Previous reports showed that HBV variants in OBI-related HCC are different from those in HBsAg-positive HCC. In the present study, HBV quasispecies based on the pre-S/S gene in OBI-related HCC patients were examined by high throughput sequencing and compared with those in HBsAg-positive HCC.MethodsNineteen tissue samples (9 OBI-related and 10 HBsAg-positive non-cancerous tissues) were collected at the time of surgery at Kobe University Hospital. The quasispecies with more than 1% variation in the pre-S/S region were isolated and analysed by ultra-deep sequencing.ResultsThere were no significant differences in the major HBV populations, which exhibit more than 20% variation within the entire pre-S/S region, between OBI-related HCC and HBsAg-positive HCC. However, the prevalences of major populations with pre-S2 region mutations and of minor populations with polymerized human serum albumin-binding domain mutations were significantly higher in OBI-related HCC than in HBsAg-positive HCC. Moreover, the major variant populations associated with the B-cell epitope, located within the pre-S1 region, and the a determinant domain, located in the S region, were detected frequently in HBsAg-positive HCC. The minor populations of variants harbouring the W4R, L30S, Q118R/Stop, N123D and S124F/P mutations in the pre-S region and the L21F/S and L42F/S mutations in the S region were detected more frequently in OBI-related HCC than in HBsAg-positive HCC.ConclusionsUltra-deep sequencing revealed that the B-cell epitope domain in the pre-S1 region and alpha determinant domain in the S region were variable in HBsAg-positive HCC, although the quasispecies associated with the pre-S2 region were highly prevalent in OBI-related HCC.Trial registrationRef: R000034382/UMIN000030113; Retrospectively registered 25 November 2017.