Current progress in the development of a prophylactic vaccine for HIV-1

Since its discovery and characterization in the early 1980s as a virus that attacks the immune system, there has been some success for the treatment of human immunodeficiency virus-1 (HIV-1) infection. However, due to the overwhelming public health impact of this virus, a vaccine is needed urgently. Despite the tireless efforts of scientist and clinicians, there is still no safe and effective vaccine that provides sterilizing immunity. A vaccine that provides sterilizing immunity against HIV infection remains elusive in part due to the following reasons: 1) degree of diversity of the virus, 2) ability of the virus to evade the hosts’ immunity, and 3) lack of appropriate animal models in which to test vaccine candidates. There have been several attempts to stimulate the immune system to provide protection against HIV-infection. Here, we will discuss attempts that have been made to induce sterilizing immunity, including traditional vaccination attempts, induction of broadly neutralizing antibody production, DNA vaccines, and use of viral vectors. Some of these attempts show promise pending continued research efforts

Therapeutic efficacy of an oncolytic adenovirus containing RGD ligand in minor capsid protein IX and Fiber, Δ24DoubleRGD, in an ovarian cancer model

Ovarian cancer is the leading cause of gynecological disease death despite advances in medicine. Therefore, novel strategies are required for ovarian cancer therapy. Conditionally replicative adenoviruses (CRAds), genetically modified as anti-cancer therapeutics, are one of the most attractive candidate agents for cancer therapy. However, a paucity of coxsackie B virus and adenovirus receptor (CAR) expression on the surface of ovarian cancer cells has impeded treatment of ovarian cancer using this approach.This study sought to engineer a CRAd with enhanced oncolytic ability in ovarian cancer cells, “Δ24DoubleRGD.” Δ24DoubleRGD carries an arginine-glycine-aspartate (RGD) motif incorporated into both fiber and capsid protein IX (pIX) and its oncolytic efficacy was evaluated in ovarian cancer. In vitro analysis of cell viability showed that infection of ovarian cancer cells with Δ24DoubleRGD leads to increased cell killing relative to the control CRAds. Data from this study suggested that not only an increase in number of RGD motifs on the CRAd capsid, but also a change in the repertoir of targeted integrins could lead to enhanced oncolytic potency of Δ24DoubleRGD in ovarian cancer cells in vitro. In an intraperitoneal model of ovarian cancer, mice injected with Δ24DoubleRGD showed, however, a similar survival rate as mice treated with control CRAds

The Proterozoic Vazante hypogene zinc silicate district, Minas Gerais, Brazil: a review of the ore system applied to mineral exploration

The Proterozoic Vazante zinc silicate district in Minas Gerais, Brazil, hosts world-class hypogene willemite deposits in dolomitic rocks interbedded with siliciclastic rocks deposited in subtidal to supratidal environments. Willemite ore bodies are structurally controlled along regional NE-trending structures which are interpreted as being active during the Neoproterozoic Brasiliano orogeny. The hydrothermal alteration is characterized by an early stage of Fe-dolomite, which replaced the host dolomitic rocks, followed by precipitation of minor sphalerite and then hematite and willemite. Elements commonly enriched in the zinc ore include As, Ba, Be, Bi, Cd, Co, Fe, Ge, In, Mo, Ni, Sb, Se, U, V and W. Mineralogical, fluid inclusion and isotopic data indicates that mixing of S-poor metalliferous saline fluids with meteoric water favored the formation of willemite ore. Carbonaceous phyllites from the underlying thick siliciclastic sequence show evidence of early enrichment in zinc (and ore-related metals) and remobilization, respectively, prior to and during the Brasiliano orogenic event. This unit is interpreted as a possible source of ore-related elements. It is proposed that during the Brasiliano orogeny, hot (T > 170 degrees C) saline fluids (>15 wt % eq. NaCl) leached metals from siliciclastic source rocks and precipitated willemite ore in the overlying dolomitic sequence along structures that favored mixing with oxidizing meteoric water

Assessing the Impact of Farm-Management Practices on Ecosystem Services in European Agricultural Systems: A Rapid Evidence Assessment

Many farm-management practices focus on maximizing production, while others better reconcile production with the regulation of ecological processes and sociocultural identity through the provisioning of ecosystem services (ESs). Though many studies have evaluated the performance of management practices against ES supply, these studies often focused on only a few practices simultaneously. Here, we incorporate 23 distinct management practices in a rapid evidence assessment to draw more comprehensive conclusions on their supply potential across 14 ESs in European agriculture. The results are visualized using performance indicators that quantify the ES-supply potential of a given management practice. In total, 172 indicators are calculated, among which cover crops are found to have the strongest positive impact on pollination-supply potential, while extensive livestock management is found to have the strongest negative impact for the supply potential for habitat creation/protection. The indicators also provide insight into the state of the peer-reviewed literature. At both the farm and territorial levels, the literature noticeably fails to evaluate cultural services. Further, disparities between the number of indicators composed at the farm and territorial levels indicate a systematic bias in the literature toward the assessment of smaller spatial levels

Parallel imaging: is GRAPPA a useful acquisition tool for MR imaging intended for volumetric brain analysis?

<p>Abstract</p> <p>Background</p> <p>The work presented here investigates parallel imaging applied to T1-weighted high resolution imaging for use in longitudinal volumetric clinical studies involving Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI) patients. This was in an effort to shorten acquisition times to minimise the risk of motion artefacts caused by patient discomfort and disorientation. The principle question is, "Can parallel imaging be used to acquire images at 1.5 T of sufficient quality to allow volumetric analysis of patient brains?"</p> <p>Methods</p> <p>Optimisation studies were performed on a young healthy volunteer and the selected protocol (including the use of two different parallel imaging acceleration factors) was then tested on a cohort of 15 elderly volunteers including MCI and AD patients. In addition to automatic brain segmentation, hippocampus volumes were manually outlined and measured in all patients. The 15 patients were scanned on a second occasion approximately one week later using the same protocol and evaluated in the same manner to test repeatability of measurement using images acquired with the GRAPPA parallel imaging technique applied to the MPRAGE sequence.</p> <p>Results</p> <p>Intraclass correlation tests show that almost perfect agreement between repeated measurements of both segmented brain parenchyma fraction and regional measurement of hippocampi. The protocol is suitable for both global and regional volumetric measurement dementia patients.</p> <p>Conclusion</p> <p>In summary, these results indicate that parallel imaging can be used without detrimental effect to brain tissue segmentation and volumetric measurement and should be considered for both clinical and research studies where longitudinal measurements of brain tissue volumes are of interest.</p

Sex-related differences in aging rate are associated with sex chromosome system in amphibians

Sex-related differences in mortality are widespread in the animal kingdom. Although studies have shown that sex determination systems might drive lifespan evolution, sex chromosome influence on aging rates have not been investigated so far, likely due to an apparent lack of demographic data from clades including both XY (with heterogametic males) and ZW (heterogametic females) systems. Taking advantage of a unique collection of capture-recapture datasets in amphibians, a vertebrate group where XY and ZW systems have repeatedly evolved over the past 200 million years, we examined whether sex heterogamy can predict sex differences in aging rates and lifespans. We showed that the strength and direction of sex differences in aging rates (and not lifespan) differ between XY and ZW systems. Sex-specific variation in aging rates was moderate within each system, but aging rates tended to be consistently higher in the heterogametic sex. This led to small but detectable effects of sex chromosome system on sex differences in aging rates in our models. Although preliminary, our results suggest that exposed recessive deleterious mutations on the X/Z chromosome (the "unguarded X/Z effect") or repeat-rich Y/W chromosome (the "toxic Y/W effect") could accelerate aging in the heterogametic sex in some vertebrate clades.Peer reviewe