Cell and molecular biology of intervertebral disc degeneration: current understanding and implications for potential therapeutic strategies

Intervertebral disc degeneration (IDD) is a chronic, complex process associated with low back pain; mechanisms of its occurrence have not yet been fully elucidated. Its process is not only accompanied by morphological changes, but also by systematic changes in its histological and biochemical properties. Many cellular and molecular mechanisms have been reported to be related with IDD and to reverse degenerative trends, abnormal conditions of the living cells and altered cell phenotypes would need to be restored. Promising biological therapeutic strategies still rely on injection of active substances, gene therapy and cell transplantation. With advanced study of tissue engineering protocols based on cell therapy, combined use of seeding cells, bio‐active substances and bio‐compatible materials, are promising for IDD regeneration. Recently reported progenitor cells within discs themselves also hold prospects for future IDD studies. This article describes the background of IDD, current understanding and implications of potential therapeutic strategies.     

Cellular HIV-1 DNA Levels in Drug Sensitive Strains Are Equivalent to Those in Drug Resistant Strains in Newly-Diagnosed Patients in Europe

Background

HIV-1 genotypic drug resistance is an important threat to the success of antiretroviral therapy and transmitted resistance has reached 9% prevalence in Europe. Studies have demonstrated that HIV-1 DNA load in peripheral blood mononuclear cells (PBMC) have a predictive value for disease progression, independently of CD4 counts and plasma viral load.

Methodology/Principal Findings

Molecular-beacon-based real-time PCR was used to measure HIV-1 second template switch (STS) DNA in PBMC in newly-diagnosed HIV-1 patients across Europe. These patients were representative for the HIV-1 epidemic in the participating countries and were carrying either drug-resistant or sensitive viral strains. The assay design was improved from a previous version to specifically detect M-group HIV-1 and human CCR5 alleles. The findings resulted in a median of 3.32 log₁₀ HIV-1 copies/10⁶ PBMC and demonstrated for the first time no correlation between cellular HIV-1 DNA load and transmitted drug-resistance. A weak association between cellular HIV-1 DNA levels with plasma viral RNA load and CD4⁺ T-cell counts was also reconfirmed. Co-receptor tropism for 91% of samples, whether or not they conferred resistance, was CCR5. A comparison of pol sequences derived from RNA and DNA, resulted in a high similarity between the two.

Conclusions/Significance

An improved molecular-beacon-based real-time PCR assay is reported for the measurement of HIV-1 DNA in PBMC and has investigated the association between cellular HIV-1 DNA levels and transmitted resistance to antiretroviral therapy in newly-diagnosed patients from across Europe. The findings show no correlation between these two parameters, suggesting that transmitted resistance does not impact disease progression in HIV-1 infected individuals. The CCR5 co-receptor tropism predominance implies that both resistant and non-resistant strains behave similarly in early infection. Furthermore, a correlation found between RNA- and DNA-derived sequences in the pol region suggests that genotypic drug-resistance testing could be carried out on either template.     

Trophic level modulates carabid beetle responses to habitat and landscape structure: a pan‐European study

1. Anthropogenic pressures have produced heterogeneous landscapes expected to influence diversity differently across trophic levels and spatial scales. 2. We tested how activity density and species richness of carabid trophic groups responded to local habitat and landscape structure (forest percentage cover and habitat richness) in 48 landscape parcels (1 km²) across eight European countries. 3. Local habitat affected activity density, but not species richness, of both trophic groups. Activity densities were greater in rotational cropping compared with other habitats; phytophage densities were also greater in grassland than forest habitats. 4. Controlling for country and habitat effects, we found general trophic group responses to landscape structure. Activity densities of phytophages were positively correlated, and zoophages uncorrelated, with increasing habitat richness. This differential functional group response to landscape structure was consistent across Europe, indicated by a lack of a country × habitat richness interaction. Species richness was unaffected by landscape structure. 5. Phytophage sensitivity to landscape structure may arise from relative dependency on seed from ruderal plants. This trophic adaptation, rare in Carabidae, leads to lower phytophage numbers, increasing vulnerability to demographic and stochastic processes that the greater abundance, species richness, and broader diet of the zoophage group may insure against.     

A review of the chemistry and uses of crocins and crocetin,the carotenoid natural dyes in saffron,with particular emphasis on applications as colorants including their use as biological stains

The perennial flowering plant, saffron crocus (Crocus sativus L.), is the source of the most expensive spice in the world. The dried stigmas of saffron flowers are the source of a natural dye, saffron, which has been used from ancient times for dyeing silk and fabric rugs, and for painting; it also has been used for cooking and in medicine. The yellow compounds present in the dye include crocins, which are 20-carbon water soluble glycosyl derivatives of the carotenoid, crocetin, and the dicarboxylic acid itself. We review the chemistry of these compounds and discuss various applications of saffron as a natural dye. We review in particular the use of saffron or its constituents in histopathologic techniques.     

Are parental care trade‐offs in shorebirds driven by parental investment or sexual selection?

Sexual selection, mating systems and parental behaviour are closely linked, although the exact nature of their relationship is controversial. The parental investment hypothesis (PIH) states that parental care disparity drives sexual selection intensity, because the sex providing less care competes for the sex that provides more. In contrast, the sexual selection hypothesis (SSH) asserts that more intense sexual selection on males leads to reduced male parental investment. We tested these hypotheses using directional phylogenetic comparative methods in shorebirds, which have an unusually diverse array of breeding systems. Changes in parental care and sexual selection intensity were tightly correlated, and we carried out three sets of analyses focusing on changes in male behaviour, female behaviour and in either sex. The results from the analyses were consistent with both PIH and SSH, although the patterns in male transition were sensitive to model values. We propose two explanations for these results. First, phylogenetic transitions may be idiosyncratic so that they depend on the ecological circumstances of individual species. Second, transitions in social traits, such as breeding systems, may be rapid and take place in ecological time, so directional phylogenetic methods that work through longer time scales may not infer accurately the timing and direction of all changes.     

New Atropisomeric Amino Alcohol Ligands for Enantioselective Addition of Diethylzinc to Aldehydes

Efficient synthesis of several new atropisomeric amino alcohols having 1‐phenyl‐1H‐pyrrole skeleton are reported. Steric arrangements of the products were confirmed by a single‐crystal X‐ray measurement. The consequences of the size of the N‐substituents on enantioinduction were examined by employing the enantioselective catalytic addition of diethylzinc to a series of substituted benzaldehydes (yields 91–97%, up to 85% enantiomeric excess). The special effect of the ortho methoxy group of the substrate on the enantioinduction is also interpreted. Chirality 27:216–222, 2015. © 2014 Wiley Periodicals, Inc.     

Seroprevalence of herpes simplex virus type 2 in adult HIV-infected patients and blood donors in Croatia

The present study estimates herpes simplex virus type 2 (HSV-2) seroprevalence and evaluates its association with age, sex, human herpesvirus type 8 (HHV-8) and human immunodeficiency virus (HIV) among adults in Croatia. A cross-sectional survey included 166 HIV-infected patients and 219 blood donors. Antibodies against HSV-2 were determined by enzyme immunoassays based on gG2 recombinant glycoprotein. HSV-2 seroprevalence was 45.8% in HIV-infected patients and 8.7% in blood donors (p < 0.0001; OR 8.8; 95% CI 5.05-15.49). Independent predictors of HSV-2 seropositivity were HIV infection (OR 11.0; 95% CI 5.93-20.41), female gender (OR 2.28; 95% CI 1.22-4.26), older age (OR 3.93; 95% CI 2.74-7.11), and HHV-8 seropositivity (OR 2.72; 95% CI 1.09-6.75). Understanding the epidemiology of HSV-2 is a critical first step in designing interventions to decrease HSV-2 and HIV transmission. The association of HSV-2 with HIV infection and HHV-8 antibodies suggests a similar transmission route.     

Frequency of HIV-1 viral load monitoring of patients initially successfully treated with combination antiretroviral therapy

Background

Although considered an essential tool for monitoring the effect of combination antiretroviral treatment (CART), HIV-1 RNA (viral load, VL) testing is greatly influenced by cost and availability of resources.

Objectives

To examine whether HIV infected patients who were initially successfully treated with CART have less frequent monitoring of VL over time and whether CART failure and other HIV-disease and sociodemographic characteristics are associated with less frequent VL testing.

Methods

The study included patients who started CART in the period 1999–2004, were older than 18 years, CART naive, had two consecutive viral load measurements of <400 copies/ml after 5 months of treatment and had continuous CART during the first 15 months. The time between two consecutive visits (days) was the outcome and associated factors were assessed using linear mixed models.

Results

We analyzed a total of 128 patients with 1683 visits through December 2009. CART failure was observed in 31 (24%) patients. When adjusted for the follow-up time, the mean interval between two consecutive VL tests taken in patients before CART failure (155.2 days) was almost identical to the interval taken in patients who did not fail CART (155.3 days). On multivariable analysis, we found that the adjusted estimated time between visits was 150.9 days before 2003 and 177.6 in 2008/2009. A longer time between visits was observed in seafarers compared to non-seafarers; the mean difference was 30.7 days (95% CI, 14.0 to 47.4; p<0.001); and in individuals who lived more than 160 kilometers from the HIV treatment center (mean difference, 16 days, p = 0.010).

Conclusions

Less frequent monitoring of VL became common in recent years and was not associated with failure. We identified seafarers as a population with special needs for CART monitoring and delivery.