Interaction between Plate Make and Protein in Protein Crystallisation Screening

Background: Protein crystallisation screening involves the parallel testing of large numbers of candidate conditions with the aim of identifying conditions suitable as a starting point for the production of diffraction quality crystals. Generally, condition screening is performed in 96-well plates. While previous studies have examined the effects of protein construct, protein purity, or crystallisation condition ingredients on protein crystallisation, few have examined the effect of the crystallisation plate

Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia

Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons. The resulting protein network is enriched for common variant risk of schizophrenia in Europeans and East Asians, is down-regulated in layer 5/6 cortical neurons of individuals affected by schizophrenia, and can complement fine-mapping and eQTL data to prioritize additional genes in GWAS loci. A sub-network centered on HCN1 is enriched for common variant risk and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings showcase brain cell-type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in schizophrenia and its related disorders

A correction for sample overlap in genome-wide association studies in a polygenic pleiotropy-informed framework.

BACKGROUND: There is considerable evidence that many complex traits have a partially shared genetic basis, termed pleiotropy. It is therefore useful to consider integrating genome-wide association study (GWAS) data across several traits, usually at the summary statistic level. A major practical challenge arises when these GWAS have overlapping subjects. This is particularly an issue when estimating pleiotropy using methods that condition the significance of one trait on the signficance of a second, such as the covariate-modulated false discovery rate (cmfdr). RESULTS: We propose a method for correcting for sample overlap at the summary statistic level. We quantify the expected amount of spurious correlation between the summary statistics from two GWAS due to sample overlap, and use this estimated correlation in a simple linear correction that adjusts the joint distribution of test statistics from the two GWAS. The correction is appropriate for GWAS with case-control or quantitative outcomes. Our simulations and data example show that without correcting for sample overlap, the cmfdr is not properly controlled, leading to an excessive number of false discoveries and an excessive false discovery proportion. Our correction for sample overlap is effective in that it restores proper control of the false discovery rate, at very little loss in power. CONCLUSIONS: With our proposed correction, it is possible to integrate GWAS summary statistics with overlapping samples in a statistical framework that is dependent on the joint distribution of the two GWAS

Variability in Working Memory Performance Explained by Epistasis vs Polygenic Scores in the ZNF804A Pathway

Importance: We investigated the variation in neuropsychological function explained by risk alleles at the psychosis susceptibility gene ZNF804A and its interacting partners using single nucleotide polymorphisms (SNPs), polygenic scores, and epistatic analyses. Of particular importance was the relative contribution of the polygenic score vs epistasis in variation explained. Objectives To (1) assess the association between SNPs in ZNF804A and the ZNF804A polygenic score with measures of cognition in cases with psychosis and (2) assess whether epistasis within the ZNF804A pathway could explain additional variation above and beyond that explained by the polygenic score. Design, Setting, and Participants: Patients with psychosis (n = 424) were assessed in areas of cognitive ability impaired in schizophrenia including IQ, memory, attention, and social cognition. We used the Psychiatric GWAS Consortium 1 schizophrenia genome-wide association study to calculate a polygenic score based on identified risk variants within this genetic pathway. Cognitive measures significantly associated with the polygenic score were tested for an epistatic component using a training set (n = 170), which was used to develop linear regression models containing the polygenic score and 2-SNP interactions. The best-fitting models were tested for replication in 2 independent test sets of cases: (1) 170 individuals with schizophrenia or schizoaffective disorder and (2) 84 patients with broad psychosis (including bipolar disorder, major depressive disorder, and other psychosis). Main Outcomes and Measures: Participants completed a neuropsychological assessment battery designed to target the cognitive deficits of schizophrenia including general cognitive function, episodic memory, working memory, attentional control, and social cognition. Results: Higher polygenic scores were associated with poorer performance among patients on IQ, memory, and social cognition, explaining 1% to 3% of variation on these scores (range, P = .01 to .03). Using a narrow psychosis training set and independent test sets of narrow phenotype psychosis (schizophrenia and schizoaffective disorder), broad psychosis, and control participants (n = 89), the addition of 2 interaction terms containing 2 SNPs each increased the R2 for spatial working memory strategy in the independent psychosis test sets from 1.2% using the polygenic score only to 4.8% (P = .11 and .001, respectively) but did not explain additional variation in control participants. Conclusions and Relevance: These data support a role for the ZNF804A pathway in IQ, memory, and social cognition in cases. Furthermore, we showed that epistasis increases the variation explained above the contribution of the polygenic score

Pseudomembranous Colitis

INTRODUCTION: Pseudomembranous colitis, also known as a Clostridium difficile colitis is a potentially life-threatening acute infectious colitis.  This colitis results from the effects of toxins produced by the overgrowth of Clostridium difficile, usually as a result of broad-spectrum antibiotic therapy. Pseudomembranous colitis is characterized endoscopically by yellowish plaques forming pseudomembranes on the colonic mucosa. CASE PRESENTATION: We are presenting a case of a 68-year-old woman who came to the Emergency Department in our hospital, complaining of abdominal tenderness, episodes of diarrhea, nausea and vomiting. She had elevated white blood cell count. The plain radiographic findings were not specific. The contrast-enhanced CT played a key role in establishing the diagnosis. The CT findings included: wall thickening of the entire colon with intense enhancement of the mucosa and extensive hypodensity of the submucosal layer due to oedema. Ascites was also present. The diagnosis of pseudomembranous colitis was later confirmed by the presence of toxins in stool assays. Very often, like in our case, Clostridium difficile colitis may present with symptoms suggestive of acute abdomen, which can lead to unwarranted laparotomy.CONCLUSION: CT has been used increasingly in recent years for the evaluation of acute abdominal diseases. CT can be very helpful in suggesting the diagnosis of pseudomembranous colitis and thus avoid unwarranted laparotomy

INHIBITORY ACTIVITY OF VAGINAL LACTOBACILLI AGAINST HUMAN PATHOGENS

ABSTRAC

Carcass traits and meat quality of different slow growing and fast growing broiler chickens

Abstract. The experiment was conducted in the breeder farm of department Population genetics, reproduction and technologies of poultry and rabbits at the Agriculture Institute of Stara Zagora. Five lines from the National Gene Pool of Bulgaria: line Ss (Sussex), line E (Barred Plymouth Rock), line NG (New Hampshire), line F (NG x Red Rhode Island), line L (White Plymouth Rock) were used as maternal forms in the crossing schedule and line M (Cornish) as a paternal form for production of slow-growing broilers. The birds were grown to 84 days. Feeding was done with compound feeds according to the age: starter (1/14 days of age), grower (14/28 days of age), finisher (28/84 days of age). By the end of the experiment, slaughter analysis was performed with 3 female and 3 male broiler chickens per group with live weight corresponding to the average of each genotype. The live weight was determined, as well as the grill weight, the weights of cuts (breast, thighs, wings), edible offal (heart, liver, gizzard) and abdominal fat. On the basis of these data, the slaughter yield and body parts ratios were calculated. The data for the live body weights of birds at slaughtering indicated the highest values for group V – 4040g, followed by groups ІV and ІІ – 3271.67g and 3186.67g, respectively (p<0.05). There was a statistically significant difference between the sexes with superiority of male birds (p<0.001). In the other 3 groups, breast meat percentage ranged from 19.48 to 19.84%. The share of thighs from the grill was the greatest in slow-growing chickens from group II – 33.01%, followed by group І – 32.35%, group IV – 32.18%, and the lowest- in groups ІІІ and V (31.91% and 31.18%, respectively). The analysis of data exhibited a significant effect of the genotype on water content of breast meat (resp. Dry matter), with lower values in slow-growing birds from group III – 73.19% (p<0.05), whereas in the other groups it ranged between 73.44 and 73.62%. The dry matter higher percentage was associated with better lavor of meat. The analysis of the effect of genotype on meat protein content showed that protein content was the highest in the breast of slow-growing chickens from group III- 24.89% and lowest in the breast meat of conventional broilers from group V – 23.86% (p<0.05). In the other 3 groups, it ranged from 24.55 to 24.59%. The protein content of thighs was the lowest in slow-growing birds from group I- 19.49%, and the difference was the highest when compared to groups II and III, also slow-growing (p<0.05). With respect to the thigh fat content, it was the highest in slow-growing chickens from group IV (5.84%), followed by fast-growing from group V (5.33%) and the lowest- in slow-growing birds from group І – 4.12% (p<0.05). The analysis of data showed a statistically significant effect of the sex on water content (p<0.001), fat (p<0.001) and ash (p<0.01). In males, thigh meat contained water and ash and in females more fat. The interaction of genotype and sex effects were important for thigh meat fat content, with highest values in fast-growing females from group V – 5.98% and lowest in slowly growing males from group I – 3.88% (p<0.001). Weak but statistically significant interaction between both factors was found with respect to thigh protein and ash (p<0.05). The highest protein content was established in slow-growing females from group IV (19.81%), whereas thigh ash was with highest percentage in slow-growing males from group II (1.11%