The Deafness-Associated Mitochondrial DNA Mutation at Position 7445, Which Affects tRNASer(UCN) Precursor Processing, Has Long-Range Effects on NADH Dehydrogenase Subunit ND6 Gene Expression

The pathogenetic mechanism of the deafness-associated mitochondrial DNA (mtDNA) T7445C mutation has been investigated in several lymphoblastoid cell lines from members of a New Zealand pedigree exhibiting the mutation in homoplasmic form and from control individuals. We show here that the mutation flanks the 3' end of the tRNASer(UCN) gene sequence and affects the rate but not the sites of processing of the tRNA precursor. This causes an average reduction of ~70% in the tRNASer(UCN) level and a decrease of ~45% in protein synthesis rate in the cell lines analyzed. The data show a sharp threshold in the capacity of tRNASer(UCN) to support the wild-type protein synthesis rate, which corresponds to ~40% of the control level of this tRNA. Strikingly, a 7445 mutation-associated marked reduction has been observed in the level of the mRNA for the NADH dehydrogenase (complex I) ND6 subunit gene, which is located ~7 kbp upstream and is cotranscribed with the tRNASer(UCN) gene, with strong evidence pointing to a mechanistic link with the tRNA precursor processing defect. Such reduction significantly affects the rate of synthesis of the ND6 subunit and plays a determinant role in the deafness-associated respiratory phenotype of the mutant cell lines. In particular, it accounts for their specific, very significant decrease in glutamate- or malate-dependent O2 consumption. Furthermore, several homoplasmic mtDNA mutations affecting subunits of NADH dehydrogenase may play a synergistic role in the establishment of the respiratory phenotype of the mutant cells

Preventing human immunodeficiency virus infection among sexual assault survivors in Cape Town, South Africa: an observational study.

We describe 131 South African sexual assault survivors offered HIV post-exposure prophylaxis (PEP). While the median days completed was 27 (IQR 27, 28), 34% stopped PEP or missed doses. Controlling for baseline symptoms, PEP was not associated with symptoms (OR = 1.30, 95% CI = 0.66, 2.64). Factors associated with unprotected sex included prior unprotected sex (OR = 6.46, 95% CI = 3.04, 13.74), time since the assault (OR = 1.33, 95% CI = 1.12, 1.57) and age (OR = 1.30, 95% CI = 1.08, 1.57). Trauma counseling was protective (OR = 0.18, 95% CI = 0.05, 0.58). Four instances of seroconversion were observed by 6 months (risk = 3.7%, 95% CI = 1.0, 9.1). Proactive follow-up is necessary to increase the likelihood of PEP completion and address the mental health and HIV risk needs of survivors. Adherence interventions and targeted risk reduction counseling should be provided to minimize HIV acquisition

The privilege of induction avoidance and calcineurin inhibitors withdrawal in 2 haplotype HLA matched white kidney transplantation

BACKGROUND: White recipients of 2-haplotype HLA-matched living kidney transplants are perceived to be of low immunologic risk. Little is known about the safety of induction avoidance and calcineurin inhibitor withdrawal in these patients. METHODS: We reviewed our experience at a single center and compared it to Organ Procurement and Transplantation Network (OPTN) registry data and only included 2-haplotype HLA-matched white living kidney transplants recipients between 2000 and 2013. RESULTS: There were 56 recipients in a single center (where no induction was given) and 2976 recipients in the OPTN. Among the OPTN recipients, 1285 received no induction, 903 basiliximab, 608 thymoglobulin, and 180 alemtuzumab. First-year acute rejection rates were similar after induction-free transplantation among the center and induced groups nationally. Compared with induction-free transplantation in the national data, there was no decrease in graft failure risk over 13 years with use of basiliximab (adjusted hazard ratio [aHR], 0.86; confidence interval [CI], 0.68-1.08), Thymoglobulin (aHR, 0.92; CI, 0.7-1.21) or alemtuzumab (aHR, 1.18; CI, 0.72-1.93). Among induction-free recipients at the center, calcineurin inhibitor withdrawal at 1 year (n = 27) did not significantly impact graft failure risk (HR,1.62; CI, 0.38-6.89). CONCLUSIONS: This study may serve as a foundation for further studies to provide personalized, tailored, immunosuppression for this very low-risk population of kidney transplant patients

Simulation for the oblique impact of a lattice system

The oblique collision between an elastic disk and an elastic wall is numerically studied. We investigate the dependency of the tangential coefficient of restitution on the incident angle of impact. From the results of simulation, our model reproduces experimental results and can be explained by a phenomenological theory of the oblique impact.Comment: 30 pages, 9 figures, submitted to J. Phys. Soc. Japa

PaleoBank, A Relational Database for Invertebrate Paleontology: The Data Model

7 p., 1 fig., 2 tables.http://paleo.ku.edu/contributions.htm

Direct observation of the evolving metal–support interaction of individual cobalt nanoparticles at the titania and silica interface

Understanding the metal–support interaction (MSI) is crucial to comprehend how the catalyst support affects performance and whether this interaction can be exploited in order to design new catalysts with enhanced properties. Spatially resolved soft X-ray absorption spectroscopy (XAS) in combination with Atomic Force Microscopy (AFM) and Scanning Helium Ion-Milling Microscopy (SHIM) has been applied to visualise and characterise the behaviour of individual cobalt nanoparticles (CoNPs) supported on two-dimensional substrates (SiOxSi(100) (x < 2) and rutile TiO2(110)) after undergoing reduction–oxidation–reduction (ROR). The behaviour of the Co species is observed to be strongly dependent on the type of support. For SiOxSi a weaker MSI between Co and the support allows a complete reduction of CoNPs although they migrate and agglomerate. In contrast, a stronger MSI of CoNPs on TiO2 leads to only a partial reduction under H2 at 773 K (as observed from Co L3-edge XAS data) due to enhanced TiO2 binding of surface-exposed cobalt. SHIM data revealed that the interaction of the CoNPs is so strong on TiO2, that they are seen to spread at and below the surface and even to migrate up to ∼40 nm away. These results allow us to better understand deactivation phenomena and additionally demonstrate a new understanding concerning the nature of the MSI for Co/TiO2 and suggest that there is scope for careful control of the post-synthetic thermal treatment for the tuning of this interaction and ultimately the catalytic performance