Breed differences in PCV2 uptake and disintegration in porcine monocytes

Porcine circovirus type 2 (PCV2) is associated with various diseases which are designated as PCV2-associated diseases (PCVADs). Their severity varies among breeds. In the diseased pigs, virus is present in monocytes, without replication or full degradation. PCV2 entry and viral outcome in primary porcine monocytes and the role of monocytes in PCV2 genetic susceptibility have not been studied. Here, virus uptake and trafficking were analyzed and compared among purebreds Pietrain, Landrace and Large White and hybrid Pietrain x Topigs20. Viral capsids were rapidly internalized into monocytes, followed by a slow disintegration to a residual level. PCV2 uptake was decreased by chlorpromazine, cytochalasin D and dynasore. The internalized capsids followed the endosomal trafficking pathway, ending up in lysosomes. PCV2 genome was nicked by lysosomal DNase II in vitro, but persisted in monocytes in vivo. Monocytes from purebred Pietrain and the hybrid showed a higher level of PCV2 uptake and disintegration, compared to those from Landrace and Large White. In conclusion, PCV2 entry occurs via clathrin-mediated endocytosis. After entry, viral capsids are partially disintegrated, while viral genomes largely escape from the pathway to avoid degradation. The degree of PCV2 uptake and disintegration differ among pig breeds

Aligning Recommendation and Conversation via Dual Imitation

Human conversations of recommendation naturally involve the shift of interests which can align the recommendation actions and conversation process to make accurate recommendations with rich explanations. However, existing conversational recommendation systems (CRS) ignore the advantage of user interest shift in connecting recommendation and conversation, which leads to an ineffective loose coupling structure of CRS. To address this issue, by modeling the recommendation actions as recommendation paths in a knowledge graph (KG), we propose DICR (Dual Imitation for Conversational Recommendation), which designs a dual imitation to explicitly align the recommendation paths and user interest shift paths in a recommendation module and a conversation module, respectively. By exchanging alignment signals, DICR achieves bidirectional promotion between recommendation and conversation modules and generates high-quality responses with accurate recommendations and coherent explanations. Experiments demonstrate that DICR outperforms the state-of-the-art models on recommendation and conversation performance with automatic, human, and novel explainability metrics.Comment: EMNLP 202

Effect of bifidobacteria on intestinal injury and flora in a mouse model of ulcerative colitis

Purpose: To investigate the effect of bifidobacteria on intestinal injury and flora in a mouse model of ulcerative colitis (UC).Methods: Mouse model of UC was produced using dextran sulphate sodium (DSS). The mice were divided into seven groups, viz, reference group, MRS-L medium-negative control group, mesalaminepositive control group, high dose bifidobacteria (MIMBb75) group, middle dose MIMBb75 group and low dose MIMBb75 group. Normal mice were used as control. All mice were sacrificed at day 7 of treatment, and colon length, hemoglobin concentration and intestinal flora were determined.Results: Bifidobacteria inhibited UC-induced decreases in mice hemoglobin and UC-induced colon shortening. In addition, it augmented the diversity of intestinal flora and increased the number of bacteroides and Clostridium leptum.Conclusion: Bifidobacteria plays a therapeutic role in UC via regulation of intestinal microflora.Keywords: Bifidobacteria, MIMBb75, Ulcerative colitis, Intestinal injury, Intestinal flor

Respuesta de la actividad enzimática digestiva al incremento gradual de la salinidad en el cangrejo de Shanghai maduro, Eriocheir sinensis (Decapoda: Brachyura)

Mature Chinese mitten crabs, Eriocheir sinensis, were exposed to brackish water or seawater as an obligatory part of their reproductive migration. Physiological and biochemical reorganization were needed to adapt them to this migration. To understand the digestive adjustments of Eriocheir sinensis at biochemical level during this transformation from freshwater to seawater, the response of the activity of five digestive enzymes (amylase, cellulase, pepsin, trypsin and lipase) in the hepatopancreas to salinities increasing gradually from 0 (freshwater) to 35 (seawater) was analysed in mature females and males. Digestive enzymes exhibited significantly higher activities in the hepatopancreas of males than those of females, except lipase. In females, amylase, pepsin and trypsin activities began to decrease significantly as the salinity reached 28, and cellulase activity decreased at 35; in males, a considerable decrease in the activity of digestive enzymes, except lipase, was observed at 21 and higher salinities, while an increase was observed at 14. Reduced enzyme activities at elevated salinities suggest that the digestive capacity of crabs for diets becomes weak, and all these digestive enzymes participated in digestive adjustments during osmoregulation. The initial salinity which induced the decrease of enzyme activity was lower in males than in females, indicating that females were more tolerant to elevated salinities than males from the point of digestive biochemical modulation.Se expusieron cangrejos de Shanghai maduros (Eriocheir sinensis) a agua salobre o agua marina obligatoriamente durante la migración reproductora. A fin de que los ejemplares se adaptaran a esta migración, fue preciso proceder a una reorganización fisiológica y bioquímica. Con objeto de estudiar los ajustes digestivos de carácter bioquímico del Eriocheir sinensisdurante la transformación del agua dulce en agua marina, se analizó la reacción de la actividad en el hepatopáncreas de cinco enzimas digestivas (amilasa, celulasa, pepsina, tripsina y lipasa) a un aumento gradual de la salinidad, desde 0 ppt (agua dulce) hasta 35 ppt (agua marina), en ejemplares maduros machos y hembras. Las enzimas digestivas mostraron un grado de actividad notablemente mayor en el hepatopáncreas de los machos que en el de las hembras, con excepción de la lipasa. En las hembras, la actividad de la amilasa, la pepsina y la tripsina comenzó a reducirse notablemente cuando la salinidad alcanzó las 28 ppt, mientras que la actividad de la celulasa descendió cuando se alcanzaron las 35 ppt; en el caso de los machos, se observó un descenso muy pronunciado de la actividad enzimática digestiva a partir de las 21 ppt, aunque la actividad aumentó a las 14 ppt. La menor actividad enzimática indicaría que la capacidad digestiva de los cangrejos se reduce a niveles elevados de salinidad y que todas estas enzimas digestivas participan en los ajustes digestivos que se producen durante la osmorregulación. El nivel de salinidad inicial que indujo el descenso de la actividad enzimática fue inferior en los machos que en las hembras, lo cual indica que estas últimas mostraron una mayor tolerancia a un nivel elevado de salinidad que los machos desde el punto de vista de la modulación bioquímica del proceso digestivo

Novel Y-chromosomal microdeletions associated with non-obstructive azoospermia uncovered by high throughput sequencing of sequence-tagged sites (STSs)

Y-chromosomal microdeletion (YCM) serves as an important genetic factor in non-obstructive azoospermia (NOA). Multiplex polymerase chain reaction (PCR) is routinely used to detect YCMs by tracing sequence-tagged sites (STSs) in the Y chromosome. Here we introduce a novel methodology in which we sequence 1,787 (post-filtering) STSs distributed across the entire male-specific Y chromosome (MSY) in parallel to uncover known and novel YCMs. We validated this approach with 766 Chinese men with NOA and 683 ethnically matched healthy individuals and detected 481 and 98 STSs that were deleted in the NOA and control group, representing a substantial portion of novel YCMs which significantly influenced the functions of spermatogenic genes. The NOA patients tended to carry more and rarer deletions that were enriched in nearby intragenic regions. Haplogroup O2* was revealed to be a protective lineage for NOA, in which the enrichment of b1/b3 deletion in haplogroup C was also observed. In summary, our work provides a new high-resolution portrait of deletions in the Y chromosome.National Key Scientific Program of China [2011CB944303]; National Nature Science Foundation of China [31271244, 31471344]; Promotion Program for Shenzhen Key Laboratory [CXB201104220045A]; Shenzhen Project of Science and Technology [JCYJ20130402113131202, JCYJ20140415162543017]SCI(E)[email protected]; [email protected]; [email protected]

Genetic Evaluation of 114 Chinese Short Stature Children in the Next Generation Era: a Single Center Study

Background/Aims: The genetics of human height is a frequently studied and complex issue. However, there is limited genetic research of short stature. To uncover the subgroup of patients to have higher yield and to propose a simplified diagnostic algorithm in the next generation era. Methods: This study included 114 Chinese children with height SDS ≤ -2.5 and unknown etiology from 2014 to 2015. Target/whole exome sequencing (referred as NGS) and chromosomal microarray analysis (CMA) were performed on the enrolled patients sequentially to identify potential genetic etiologies. The samples solved by NGS and CMA were retrospectively studied to evaluate the clinical pathway of the patients following a standard diagnostic algorithm. Results: In total, a potential genetic etiology was identified in 41 (36%) patients: 38 by NGS (33.3%), two by CMA (1.8%), and an additional one by both (0.9%). There were 46 different variants in 29 genes and 2 pathogenic CNVs identified. The diagnostic yield was significantly higher in patients with facial dysmorphism or skeletal abnormalities than those without the corresponding phenotype (P=0.006 and P=0.009, respectively, Pearson’s χ2 test). Retrospectively study the cohort indicate 83.3% patients eventually would be evaluated by NGS/CMA. Conclusion: This study confirms the utility of high-throughput molecular detection techniques for the etiological diagnosis of undiagnosed short stature and suggests that NGS could be used as a primary diagnostic strategy. Patients with facial dysmorphism and/or skeletal abnormalities are more likely to have a known genetic etiology. Moving NGS forward would simplified the diagnostic algorithm

Sugar-sweetened beverage intake associations with fasting glucose and insulin concentrations are not modified by selected genetic variants in a ChREBP-FGF21 pathway : a meta-analysis

Aims/hypothesis Sugar-sweetened beverages (SSBs) are a major dietary contributor to fructose intake. A molecular pathway involving the carbohydrate responsive element-binding protein (ChREBP) and the metabolic hormone fibroblast growth factor 21 (FGF21) may influence sugar metabolism and, thereby, contribute to fructose-induced metabolic disease. We hypothesise that common variants in 11 genes involved in fructose metabolism and the ChREBP-FGF21 pathway may interact with SSB intake to exacerbate positive associations between higher SSB intake and glycaemic traits. Methods Data from 11 cohorts (six discovery and five replication) in the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided association and interaction results from 34,748 adults of European descent. SSB intake (soft drinks, fruit punches, lemonades or other fruit drinks) was derived from food-frequency questionnaires and food diaries. In fixed-effects meta-analyses, we quantified: (1) the associations between SSBs and glycaemic traits (fasting glucose and fasting insulin); and (2) the interactions between SSBs and 18 independent SNPs related to the ChREBP-FGF21 pathway. Results In our combined meta-analyses of discovery and replication cohorts, after adjustment for age, sex, energy intake, BMI and other dietary covariates, each additional serving of SSB intake was associated with higher fasting glucose (beta +/- SE 0.014 +/- 0.004 [mmol/l], p = 1.5 x 10(-3)) and higher fasting insulin (0.030 +/- 0.005 [log(e) pmol/l], p = 2.0 x 10(-10)). No significant interactions on glycaemic traits were observed between SSB intake and selected SNPs. While a suggestive interaction was observed in the discovery cohorts with a SNP (rs1542423) in the beta-Klotho (KLB) locus on fasting insulin (0.030 +/- 0.011 log(e) pmol/l, uncorrected p = 0.006), results in the replication cohorts and combined meta-analyses were non-significant. Conclusions/interpretation In this large meta-analysis, we observed that SSB intake was associated with higher fasting glucose and insulin. Although a suggestive interaction with a genetic variant in the ChREBP-FGF21 pathway was observed in the discovery cohorts, this observation was not confirmed in the replication analysis.Peer reviewe

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets

Whole-Exome Sequencing Identifies Loci Associated with Blood Cell Traits and Reveals a Role for Alternative GFI1B Splice Variants in Human Hematopoiesis

(The American Journal of Human Genetics 99, 481–488; August 4, 2016