Search

The exosome functions to regulate the cellular transcriptome through RNA biogenesis, surveillance, and decay. Mutations in Dis3, a catalytic subunit of the RNA exosome with separable endonuclease and exonuclease activities, are linked to multiple myeloma. Here we report that a cancer-associated DIS3 allele, dis3E729K, provides evidence for DIS3 functioning in mitotic fidelity in yeast. This dis3E729K allele does not induce defects in 7S→5.8S rRNA processing, although it elicits a requirement for P-body function. While it does not significantly influence cell cycle progression alone, the allele reduces the efficiency of cell cycle arrest in strains with defects in kinetochore assembly. Finally, point mutations in the exonuclease domains of yeast Dis3 elicit genome instability phenotypes; however, these DIS3 mutations do not increase DNA damage or RNA processing defects that lead to the accumulation of polyadenylated RNA in the nucleus. These data suggest that specific DIS3 activities support mitotic fidelity in yeast.

Objective: The impact of the wider social environment, such as neighbourhood characteristics, has not been examined in the development of borderline personality disorder. This study aimed to determine whether the treated incidence rate of full-threshold borderline personality disorder and sub-threshold borderline personality disorder, collectively termed borderline personality pathology, was associated with the specific neighbourhood characteristics of social deprivation and social fragmentation. Method: This study included young people, aged 15–24 years, who attended Orygen's Helping Young People Early programme, a specialist early intervention service for young people with borderline personality pathology, from 1 August 2000–1 February 2008. Diagnoses were confirmed using the Structured Clinical Interview for DSM -IV Personality Disorders, and census data from 2006 were used to determine the at-risk population and to obtain measures of social deprivation and fragmentation. Results: The study included 282 young people, of these 78.0% (n = 220) were female and the mean age was 18.3 years (SD = ±2.7). A total of 42.9% (n = 121) met criteria for full-threshold borderline personality disorder, and 57.1% (n = 161) had sub-threshold borderline personality disorder, defined as having three or four of the nine Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM -IV) borderline personality disorder criteria. There was more than a sixfold increase in the treated incidence rate of borderline personality pathology in the neighbourhoods of above average deprivation (Quartile 3) (incidence rate ratio = 6.45, 95% confidence interval: [4.62, 8.98], p < 0.001), and this was consistent in the borderline personality disorder sub-groups. This association was also present in the most socially deprived neighbourhood (Quartile 4) (incidence rate ratio = 1.63, 95% confidence interval: [1.10, 2.44]), however, only for those with sub-threshold borderline personality disorder. The treated incidence of borderline personality pathology increased incrementally with the level of social fragmentation (Quartile 3: incidence rate ratio = 1.93, 95% confidence interval: [1.37, 2.72], Quartile 4: incidence rate ratio = 2.38, 95% confidence interval: [1.77, 3.21]). Conclusion: Borderline personality pathology has a higher treated incidence in the more socially deprived and fragmented neighbourhoods. These findings have implications for funding and location of clinical services for young people with borderline personality pathology. Prospective, longitudinal studies should examine neighbourhood characteristics as potential aetiological factors for borderline personality pathology. [ABSTRACT FROM AUTHOR]

This study aimed to examine the lifetime risk of being the victim of criminal or violent offenses among young people with borderline personality disorder (BPD) features (1-9 DSM-IV criteria). Demographic and diagnostic data from 492 outpatients who attended a specialist public mental health service for 15- to 25-year-olds between January 1998 and March 2008 were linked with offending data from a state-wide police database, collected between March 1993 and June 2017, in order to establish victimization history. This included information on criminal offenses perpetrated against these young people and intervention orders implemented to protect them from being victimized by another person's violent behavior. Logistic regression analyses, adjusted for sex and co-occurring mental state disorders, were conducted on n = 378 who had complete data (76.5% females). As hypothesized, BPD diagnosis and number of BPD criteria were both significantly associated with an increased risk of being the victim of a violent offense and the complainant of a family violence intervention order. Anger and impulsivity independently predicted a higher risk of being the victim of a violent offense, while unstable relationships, impulsivity, and affective instability independently predicted a higher risk of being the complainant of a family violence intervention order. No significant association was found between BPD and the risk of being the victim of a nonviolent offense. These findings indicate that young people with any BPD features (even below the DSM diagnostic threshold) are at increased risk for victimization by interpersonal violence. Moreover, this risk increases according to the number of BPD criteria. This issue needs to be addressed by prevention and early intervention programs (e.g., by working on self-assertion and interpersonal skills, taking into account the possible influence of previous traumatizing relationship experiences). [ABSTRACT FROM AUTHOR]

Haemoglobin A1c determination from dried blood spots prepared with HemaSpot™ blood collection devices: comparison with fresh capillary blood Keywords: dried blood spots; laboratory method comparison; remote and rural; HbA1c; diabetes EN dried blood spots laboratory method comparison remote and rural HbA1c diabetes e79 e82 4 01/21/21 20210201 NES 210201 To the Editor, Long term glycaemic control in diabetes is monitored by regular determination of glycosylated haemoglobin (HbA SB 1c sb ). HbA1c determination from HemaSpot™ blood collection devices: comparison of home prepared dried blood spots with standard venous blood analysis. [Extracted from the article]

The regulated expansion of membrane contact sites, which mediate the nonvesicular exchange of lipids between organelles, requires the recruitment of additional contact site proteins. Yeast Vps13 dynamically localizes to membrane contacts that connect the ER, mitochondria, endosomes, and vacuoles and is recruited to the prospore membrane in meiosis, but its targeting mechanism is unclear. In this study, we identify the sorting nexin Ypt35 as a novel adaptor that recruits Vps13 to endosomal and vacuolar membranes. We characterize an interaction motif in the Ypt35 N terminus and identify related motifs in the prospore membrane adaptor Spo71 and the mitochondrial membrane protein Mcp1. We find that Mcp1 is a mitochondrial adaptor for Vps13, and the Vps13-Mcp1 interaction, but not Ypt35, is required when ER-mitochondria contacts are lost. All three adaptors compete for binding to a conserved six-repeat region of Vps13 implicated in human disease. Our results support a competition-based model for regulating Vps13 localization at cellular membranes. [ABSTRACT FROM AUTHOR]

The biological conversion of lignocellulosic matter into high‐value chemicals or biofuels is of increasing industrial importance as the sector slowly transitions away from nonrenewable sources. Many industrial processes involve the use of cellulolytic enzyme cocktails – a selection of glycoside hydrolases and, increasingly, polysaccharide oxygenases – to break down recalcitrant plant polysaccharides. ORFs from the genome of Teredinibacter turnerae, a symbiont hosted within the gills of marine shipworms, were identified in order to search for enzymes with desirable traits. Here, a putative T. turnerae glycoside hydrolase from family 8, hereafter referred to as TtGH8, is analysed. The enzyme is shown to be active against β‐1,4‐xylan and mixed‐linkage (β‐1,3,β‐1,4) marine xylan. Kinetic parameters, obtained using high‐performance anion‐exchange chromatography with pulsed amperometric detection and 3,5‐dinitrosalicyclic acid reducing‐sugar assays, show that TtGH8 catalyses the hydrolysis of β‐1,4‐xylohexaose with a kcat/Km of 7.5 × 107 M−1 min−1 but displays maximal activity against mixed‐linkage polymeric xylans, hinting at a primary role in the degradation of marine polysaccharides. The three‐dimensional structure of TtGH8 was solved in uncomplexed and xylobiose‐, xylotriose‐ and xylohexaose‐bound forms at approximately 1.5 Å resolution; the latter was consistent with the greater kcat/Km for hexasaccharide substrates. A 2,5B boat conformation observed in the −1 position of bound xylotriose is consistent with the proposed conformational itinerary for this class of enzyme. This work shows TtGH8 to be effective at the degradation of xylan‐based substrates, notably marine xylan, further exemplifying the potential of T. turnerae for effective and diverse biomass degradation. [ABSTRACT FROM AUTHOR]