Tau-induced neurodegeneration: mechanisms and targets

The accumulation of hyperphosphorylated tau is a common feature of several dementias. Tau is one of the brain microtubule-associated proteins. Here we discuss tau’s functions in microtubule assembly and stabilization and with regard to its interactions with other proteins. We describe and analyze important post-translational modifications: hyperphosphorylation, ubiquitination, glycation, glycosylation, nitration, polyamination, proteolysis, acetylation, and methylation. We discuss how these post-translational modifications can alter tau’s biological function. We analyze the role of mitochondrial health in neurodegeneration. We propose that microtubules could be a therapeutic target and review different approaches. Finally, we consider whether tau accumulation or its conformational change is related to tau-induced neurodegeneration, and propose a mechanism of neurodegeneration.     

Localized amyloidosis of glans penis

We describe a case of black Caribbean man who presented with penile rash for several months. The rash showed no improvement with topical steroid or anti-bacterial/fungal creams. A subsequent tissue biopsy and further investigations confirmed the diagnosis of localized amyloidosis.     

An open label Phase I trial of a live attenuated H6N1 influenza virus vaccine in healthy adults

Background

We describe the results of an open label Phase I trial of a live attenuated H6N1 influenza virus vaccine (ClinicalTrials.gov Identifier: NCT00734175).

Methods and findings

We evaluated the safety, infectivity, and immunogenicity of two doses of 10⁷ TCID₅₀ of the H6N1 Teal HK 97/AA ca vaccine, a cold-adapted and temperature sensitive live, attenuated influenza vaccine (LAIV) in healthy seronegative adults.Twenty-two participants received the first dose of the vaccine, and 18 received the second dose of vaccine 4 weeks later. The vaccine had a safety profile similar to that of other investigational LAIVs bearing avian hemagglutinin (HA) and neuraminidase (NA) genes. The vaccine was highly restricted in replication: two participants had virus detectable by rRT-PCR beyond day 1 after each dose. Antibody responses to the vaccine were also restricted: 43% of participants developed a serum antibody response as measured by any assay: 5% by hemagglutination-inhibition assay, 5% by microneutralization assay, 29% by ELISA for H6 HA-specific IgG and 24% by ELISA for H6 HA specific IgA after either 1 or 2 doses. Following the second dose, vaccine specific IgG and IgA secreting cells as measured by ELISPOT increased from a mean of 0.6 to 9.2/10⁶ PBMCs and from 0.2 to 2.2/10⁶ PBMCs, respectively.

Conclusion

The H6N1 LAIV had a safety profile similar to that of LAIV bearing other HA and NA genes, but was highly restricted in replication in healthy seronegative adults. The H6N1 LAIV was also not as immunogenic as the seasonal LAIV.     

Prevalence of sexually transmitted infections and mental health needs of female child and adolescent survivors of rape and sexual assault attending a specialist clinic

OBJECTIVES: To determine the prevalence of sexually transmitted infections (STIs) and the mental health needs of female child and adolescent survivors of rape and sexual assault who were referred to a specialist genitourinary medicine (GUM) clinic. METHOD: Retrospective case notes review of 98 females aged 16 or less, who attended over a 5 year period (1996-2000). RESULTS: The overall prevalence of STIs was 26%. Among the girls who were aged 0-12 years (n = 16), one had gonorrhoea and another had Trichomonas vaginalis infection. Prevalence of STIs in those aged 13-16 years, who were not sexually active before the index assault, was 24% and in those who gave a history of previous consensual sexual activity it was 39% (p = 0.17). Chlamydial infection was more common among the girls who disclosed previous consensual sexual activity than in those did not disclose previous sexual activity (p = 0.012). The overall prevalence of vaginal candidiasis was 17% and bacterial vaginosis 13%. More than one third of the study population gave a history of previous sexual, physical, or other abuse. 81% reported having current psychological difficulties. Mood changes and sleep disturbances were reported more frequently than other psychological symptoms; 15% attempted self harm. All types of psychological difficulties, except mood changes, were not affected by the time interval between index assault and first presentation to the clinic and the type of assailant. 29% had no involvement with social and mental health services before their attendance at the clinic CONCLUSIONS: The prevalence of STIs among female child and adolescent survivors of rape and sexual assault attending a specialist clinic was high. The range of mental health and social difficulties was wide and multiple. The importance of an early assessment for the presence of STIs and mental health difficulties was demonstrated.     

Design optimization and efficiency enhancement of axial junction nanowire solar cells utilizing a forward scattering mechanism

We report the design, optimization, and performance analysis of three axial junction nanowire solar cells (NW SCs) based on cadmium telluride (CdTe), copper indium gallium selenide (CIGS), and copper zinc tin sulfide (CZTS) with significant improvement in their optical and electrical characteristics compared to their planar counterparts. It is shown that the performance of these NW SCs can be further improved by incorporating a hemispherical indium doped tin oxide (ITO) forward scatterer on top of the ITO front contact of the solar cells. We also compare forward scatterer incorporated NW SCs with forward scatterer incorporated planar solar cells (PSCs) and observe that forward scatterers significantly enhance the absorption in both cases. We further study the optimum size and arrangement of ITO hemispheres that result in improved photocurrent. In optimum cases, the incorporation of forward scatterers leads to absorption enhancement of 7.8%, 5.36%, and 8.8% in PSCs, and 21.4%, 7.36%, and 6.02% in NW SCs, respectively, for CdTe, CIGS, and CZTS absorbers in the same order. From the absorption profile at various wavelengths, it is found that forward scatterers enhance absorption in the 450–600 nm wavelength range, while nanowires improve absorption in the 600–800 nm range, and their combination results in an improved absorption profile for the entire visible wavelength range. We also observe increased electron–hole-pair (EHP) generation rate due to increased field-scattering and light concentration at the center of the nanowire below forward scattering hemispheres, leading to 46%, 32%, and 82.5% improvement in power conversion efficiency (PCE) for the three absorber layers, respectively. The effects of Al₂O₃ and SiO₂ passivation layers surrounding the nanowires of the optimized cells are observed, and we conclude that the CIGS absorber benefits the most when the SiO₂ passivation layer is used, increasing its PCE from 29.72% to 32.43%, while the PCEs of CdTe and CZTS are unaffected by the passivation layer due to competing effects of reduced absorption and reduced surface recombination.

We report the design and performance analysis of forward scatterer incorporated axial junction nanowire solar cells based on CdTe, CIGS, and CZTS with significant improvement in their optoelectronic properties compared to their planar counterparts.     

Filarial/human immunodeficiency virus coinfection in urban southern India

The disease course of human immunodeficiency virus (HIV) is often altered by existing or newly acquired coinfections. Treatment or prevention of these concomitant infections often improves the quality and duration of life of HIV-infected persons. The impact of helminth infections on infections with HIV is less clear. However, HIV is frequently most problematic in areas where helminth infections are common. In advance of the widespread distribution of drugs for elimination of lymphatic filariasis, we assessed the prevalence of active Wuchereria bancrofti infection among HIV-positive patients in Chennai, India at two time points separated by four years. We found that the overall prevalence of W. bancrofti infections among HIV-positive persons was 5-9.5%, and there were no quantitative differences in circulating filarial antigen levels between HIV-positive and HIV-negative filarial-infected patients.