Identification of domain boundaries within the N‐termini of TAP1 and TAP2 and their importance in tapasin binding and tapasin‐mediated increase in peptide loading of MHC class I

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141680/1/imcb200564.pd

The quality control theory of aging

The quality control (QC) theory of aging is based on the concept that aging is the result of a reduction in QC of cellular systems designed to maintain lifelong homeostasis. Four QC systems associated with aging are 1) inadequate protein processing in a distressed endoplasmic reticulum (ER); 2) histone deacetylase (HDAC) processing of genomic histones and gene silencing; 3) suppressed AMPK nutrient sensing with inefficient energy utilization and excessive fat accumulation; and 4) beta-adrenergic receptor (BAR) signaling and environmental and emotional stress. Reprogramming these systems to maintain efficiency and prevent aging would be a rational strategy for increased lifespan and improved health. The QC theory can be tested with a pharmacological approach using three well-known and safe, FDA-approved drugs: 1) phenyl butyric acid, a chemical chaperone that enhances ER function and is also an HDAC inhibitor, 2) metformin, which activates AMPK and is used to treat type 2 diabetes, and 3) propranolol, a beta blocker which inhibits BAR signaling and is used to treat hypertension and anxiety. A critical aspect of the QC theory, then, is that aging is associated with multiple cellular systems that can be targeted with drug combinations more effectively than with single drugs. But more importantly, these drug combinations will effectively prevent, delay, or reverse chronic diseases of aging that impose such a tremendous health burden on our society

The Latin American Social Medicine database

BACKGROUND: Public health practitioners and researchers for many years have been attempting to understand more clearly the links between social conditions and the health of populations. Until recently, most public health professionals in English-speaking countries were unaware that their colleagues in Latin America had developed an entire field of inquiry and practice devoted to making these links more clearly understood. The Latin American Social Medicine (LASM) database finally bridges this previous gap. DESCRIPTION: This public health informatics case study describes the key features of a unique information resource intended to improve access to LASM literature and to augment understanding about the social determinants of health. This case study includes both quantitative and qualitative evaluation data. Currently the LASM database at The University of New Mexico brings important information, originally known mostly within professional networks located in Latin American countries to public health professionals worldwide via the Internet. The LASM database uses Spanish, Portuguese, and English language trilingual, structured abstracts to summarize classic and contemporary works. CONCLUSION: This database provides helpful information for public health professionals on the social determinants of health and expands access to LASM

Normalisation of cerebrospinal fluid biomarkers parallels improvement of neurological symptoms following HAART in HIV dementia – case report

BACKGROUND: Since the introduction of HAART the incidence of HIV dementia has declined and HAART seems to improve neurocognitive function in patients with HIV dementia. Currently, HIV dementia develops mainly in patients without effective treatment, though it has also been described in patients on HAART and milder HIV-associated neuropsychological impairment is still frequent among HIV-1 infected patients regardless of HAART. Elevated cerebrospinal fluid (CSF) levels of markers of neural injury and immune activation have been found in HIV dementia, but neither of those, nor CSF HIV-1 RNA levels have been proven useful as diagnostic or prognostic pseudomarkers in HIV dementia. CASE PRESENTATION: We report a case of HIV dementia (MSK stage 3) in a 57 year old antiretroviral naïve man who was introduced on zidovudine, lamivudine and ritonavir boosted indinavir, and followed with consecutive lumbar punctures before and after two and 15 months after initiation of HAART. Improvement of neurocognitive function was paralleled by normalisation of CSF neural markers (NFL, Tau and GFAP) levels and a decline in CSF and serum neopterin and CSF and plasma HIV-1 RNA levels. CONCLUSION: The value of these CSF markers as prognostic pseudomarkers of the effect of HAART on neurocognitive impairment in HIV dementia ought to be evaluated in longitudinal studies

Modelling the Effect of Temperature on Respiration Rate of Fresh Cut Papaya (Carica papaya L.) Fruits.

A respiration rate (RR) model based on Peleg’s equation was developed for predicting RRs of fresh cut papaya. Respiration data for fresh cut papaya at 3/4 maturity were generated at temperatures 5, 10, 15, 20, 25 and 30°C using a closed system. RRs was found to be significantly influenced by storage temperature and increased from 0.021 to 0.289 mL[O2]/kg·h and 0.063 to 0.393 mL[CO2]/kg·h as a function of O2 and CO2 gas concentrations, respectively. Peleg’s constant K 1 and K 2 were obtained from linear regression analysis using GraphPad Prism 5.0 software and regression coefficients have good fit with values close to unity. The model was verified to assess the capability of its predictability of the RRs over the temperatures. There was good agreement with the experimentally estimated RRs. Information derived from the model can contribute in the design of successful modified atmospheric systems for storage of fresh cut papaya

Current Developments in Intraspinal Agents for Cancer and Noncancer Pain

Since the late 1980s, intrathecal (IT) analgesic therapy has improved, and implantable IT drug delivery devices have become increasingly sophisticated. Physicians and patients now have myriad more options for agents and their combination, as well as for refining their delivery. As recently as 2007, The Polyanalgesic Consensus Conference of expert panelists updated its algorithm for drug selection in IT polyanalgesia. We review this algorithm and the emerging therapy included. This article provides an update on newly approved as well as emerging IT agents and the advances in technology for their delivery

E-Glass Fiber Reinforced Composites in Dental Applications

Fiber reinforced composites (FRCs) are more and more widely applied in dentistry to substitute for metallic restorations: periodontal splints, fixed partial dentures, endodontic posts, orthodontic appliances, and some other indirect restorations. In general in FRCs, the fiber reinforcement provides the composite structure with better biomechanical performance due to their superior properties in tension and flexure. Nowadays, the E-glass fiber is most frequently used because of its chemical resistance and relatively low cost. Growing interest is being paid to enhance its clinical performance. Moreover, various techniques are utilized to reinforce the adhesion between the fiber and the matrix. Oral conditions set special requirements and challenges for the clinical applications of FRCs. The biomechanical properties of dental materials are of high importance in dentistry, and given this, there is on-going scientific interest to develop E-glass fiber reinforced composite systems. FRCs are generally biocompatible and their toxicity is not a concern. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

Passive immunoprophylaxis and therapy with humanized monoclonal antibody specific for influenza A H5 hemagglutinin in mice

BACKGROUND: Highly pathogenic avian H5N1 influenza virus is a major public health concern. Given the lack of effective vaccine and recent evidence of antiviral drug resistance in some isolates, alternative strategies for containment of a possible future pandemic are needed. Humanized monoclonal antibodies (mAbs) that neutralize H5N1 virus could be used as prophylaxis and treatment to aid in the containment of such a pandemic. METHODS: Neutralizing mAbs against H5 hemagglutinin were humanized and introduced into C57BL/6 mice (1, 5, or 10 mg/kg bodyweight) one day prior to-, one day post- and three days post-lethal challenge with H5N1 A/Vietnam/1203/04 virus. Efficacy was determined by observation of weight loss as well as survival. RESULTS: Two mAbs neutralizing for antigenically variant H5N1 viruses, A/Vietnam/1203/04 and A/Hong Kong/213/03 were identified and humanized without loss of specificity. Both antibodies exhibited prophylactic efficacy in mice, however, VN04-2-huG1 performed better requiring only 1 mg/kg bodyweight for complete protection. When used to treat infection VN04-2-huG1 was also completely protective, even when introduced three days post infection, although higher dose of antibody was required. CONCLUSION: Prophylaxis and treatment using neutralizing humanized mAbs is efficacious against lethal challenge with A/Vietnam/1203/04, providing proof of principle for the use of passive antibody therapy as a containment option in the event of pandemic influenza

The evolution of acoustic size exaggeration in terrestrial mammals

Recent studies have revealed that some mammals possess adaptations that enable them to produce vocal signals with much lower fundamental frequency (F0) and formant frequency spacing (ΔF) than expected for their size. Although these adaptations are assumed to reflect selection pressures for males to lower frequency components and exaggerate body size in reproductive contexts, this hypothesis has not been tested across a broad range of species. Here we show that male terrestrial mammals produce vocal signals with lower ΔF (but not F0) than expected for their size in mating systems with greater sexual size dimorphism. We also reveal that males produce calls with higher than expected F0 and ΔF in species with increased sperm competition. This investigation confirms that sexual selection favours the use of ΔF as an acoustic size exaggerator, and supports the notion of an evolutionary trade-off between pre-copulatory signalling displays and sperm production