Comprehensive Analysis of the Naturally Processed Peptide Repertoire: Differences between HLA-A and B in the Immunopeptidome

The cytotoxic T cell (CTL) response is determined by the peptide repertoire presented by the HLA class I molecules of an individual. We performed an in-depth analysis of the peptide repertoire presented by a broad panel of common HLA class I molecules on four B lymphoblastoid cell-lines (BLCL). Peptide elution and mass spectrometry analysis were utilised to investigate the number and abundance of self-peptides. Altogether, 7897 unique self-peptides, derived of 4344 proteins, were eluted. After viral infection, the number of unique self-peptides eluted significantly decreased compared to uninfected cells, paralleled by a decrease in the number of source proteins. In the overall dataset, the total number of unique self-peptides eluted from HLA-B molecules was larger than from HLA-A molecules, and they were derived from a larger number of source proteins. These results in B cells suggest that HLA-B molecules possibly present a more diverse repertoire compared to their HLA-A counterparts, which may contribute to their immunodominance. This study provides a unique data set giving new insights into the complex system of antigen presentation for a broad panel of HLA molecules, many of which were never studied this extensively before.     

Cellular senescence involves an intracrine prostaglandin E2 pathway in human fibroblasts

Cyclooxygenase 2 and release of prostaglandin E₂ are involved in many responses including inflammation and are upregulated during cellular senescence. However, little is known about the role of lipid inflammatory mediators in senescence. Here, we investigated the mechanism by which the COX-2/PGE₂ axis induces senescence. Using the NS398 specific inhibitor of COX-2, we provide evidence that reactive oxygen species by-produced by the COX-2 enzymatic activity are negligible in front of the total senescence-associated oxidative stress. We therefore investigated the role of PGE₂ by invalidating the PGE₂ synthases downstream of COX-2, or the specific PGE₂ receptors, or by applying PGE₂ or specific agonists or antagonists. We evaluated the effect on senescence by evaluating the senescence-associated proliferation arrest, the percentage of senescence-associated β-galactosidase-positive cells, and the expression of senescent molecular markers such as IL-6 and MCP1. We show that PGE₂ acting on its EP specific receptors is able to induce both the onset of senescence and the maintenance of the phenotype. It did so only when the PGE₂/lactate transporter activity was enhanced, indicating that PGE₂ acts on senescence more via the pool of intracellular EP receptors than via those localized at the cell surface. Treatment with agonists, antagonists and silencing of the EP receptors by siRNA revealed that EP3 was the most involved in transducing the intracrine effects of PGE₂. Immunofluorescence experiments confirmed that EP3 was more localized in the cytoplasm than at the cell surface. Taken together, these results suggest that COX-2 contributes to the establishment and maintenance of senescence of normal human fibroblasts via an independent-ROS and a dependent-PGE₂/EPs intracrine pathway.     

Genome sequencing reveals fine scale diversification and reticulation history during speciation in Sus

Background

Elucidating the process of speciation requires an in-depth understanding of the evolutionary history of the species in question. Studies that rely upon a limited number of genetic loci do not always reveal actual evolutionary history, and often confuse inferences related to phylogeny and speciation. Whole-genome data, however, can overcome this issue by providing a nearly unbiased window into the patterns and processes of speciation. In order to reveal the complexity of the speciation process, we sequenced and analyzed the genomes of 10 wild pigs, representing morphologically or geographically well-defined species and subspecies of the genus Sus from insular and mainland Southeast Asia, and one African common warthog.

Results

Our data highlight the importance of past cyclical climatic fluctuations in facilitating the dispersal and isolation of populations, thus leading to the diversification of suids in one of the most species-rich regions of the world. Moreover, admixture analyses revealed extensive, intra- and inter-specific gene-flow that explains previous conflicting results obtained from a limited number of loci. We show that these multiple episodes of gene-flow resulted from both natural and human-mediated dispersal.

Conclusions

Our results demonstrate the importance of past climatic fluctuations and human mediated translocations in driving and complicating the process of speciation in island Southeast Asia. This case study demonstrates that genomics is a powerful tool to decipher the evolutionary history of a genus, and reveals the complexity of the process of speciation.     

The Epidemic of Hip Fractures: Are We on the Right Track?

Background

Hip fractures are a public health problem, leading to hospitalization, long-term rehabilitation, reduced quality of life, large healthcare expenses, and a high 1-year mortality. Especially older adults are at greater risk of fractures than the general population, due to the combination of an increased fall risk and osteoporosis. The aim of this study was to determine time trends in numbers and incidence rates of hip fracture-related hospitalizations and admission duration in the older Dutch population.

Methods and Findings

Secular trend analysis of all hospitalizations in the older Dutch population (≥65 years) from 1981 throughout 2008, using the National Hospital Discharge Registry. Numbers, age-specific and age-adjusted incidence rates (per 10,000 persons) of hospital admissions and hospital days due to a hip fracture were used as outcome measures in each year of the study. Between 1981 and 2008, the absolute number of hip fractures doubled in the older Dutch population. Incidence rates of hip fracture-related hospital admissions increased with age, and were higher in women than in men. The age-adjusted incidence rate increased from 52.0 to 67.6 per 10,000 older persons. However, since 1994 the incidence rate decreased (percentage annual change −0.5%, 95% CI: −0.7; −0.3), compared with the period 1981–1993 (percentage annual change 2.3%, 95% CI: 2.0; 2.7). The total number of hospital days was reduced by a fifth, due to a reduced admission duration in all age groups. A possible limitation was that data were obtained from a linked administrative database, which did not include information on medication use or co-morbidities.

Conclusions

A trend break in the incidence rates of hip fracture-related hospitalizations was observed in the Netherlands around 1994, possibly as a first result of efforts to prevent falls and fractures. However, the true cause of the observation is unknown.     

A new species of Macquaridrilus (Annelida: Clitellata: Naididae) from subantarctic Campbell Island

Macquaridrilus mcmurtrieae n. sp. is described from Campbell Island. This resembles the only other species in the genus, Macquaridrilus bennettae Jamieson, 1968, in most aspects, but shows significant differences in the anatomy of its genitalia. In particular, the spermathecal pores are dorsal rather than lateral, the spermathecae lack diverticulae, the ejaculatory duct is more stout and muscular, the vas deferens is shorter relative to other organs and the anterior prostate is compact rather than elongate. The presence of a cuticular sperm canal appears to be an apomorphy for the genus. The new species was collected from streams and tarns across the island.

http://zoobank.org/urn:lsid:zoobank.org:pub:652AF61D-CFB2-4D07-94C8-59E6FB549D5F

http://zoobank.org/urn:lsid:zoobank.org:act:984F2456-768D-48A1-87AD-4453768BAB8A     

Effect of fertilizer levels on grain yield,incidence and severity of downy mildew in pearl millet

The effect of various levels of nitrogen (0.0, 30.0, 60.0, 120.0) and phosphorus (0.0, 6.5, 13.0, 36.0) on the incidence and severity of downy mildew of pearl millet and yield of two pearl millet varieties (Zango and GB8375) were studied under field conditions in 2000 and 2001 respectively. Both nitrogen and phosphorus significantly increased incidence and severity of the disease in the two varieties. Grain yield and 1000 grain weight of the varieties also increased with nitrogen and phosphorus levels.     

New records of fungal pathogens of euphorbia inarticulata from Aseer region,south-west Saudi Arabia: Neue aufzeichnungen über fungale pathogene von euphorbia inarticulata aus der Aseer-region im südwesten Saudi Arabiens

A 12 month period survey of the fungi associated with Euphorbia inarticulata was evaluated. Sampling was concentrated mainly in Aseer region (South-West Saudi Arabia) and seven fungal species were identified as pathogens of this plant. Melampsora euphorbiae and Alternaria euphorbiicola were the most common species on this plant. Bipolaris euphorbiae, Botrytis ricini, Colletotrichum gloeosporioides, Oidium sp., Sphaceloma poinsettiase and Uromyces euphorbiae were less frequent species. These fungal pathogens were recorded for the first time on Euphorbia inarticulata in Saudi Arabia. Scanning and transmission electron microscopy revealed the colonization of M. euphorbiae, as an example, in leaf tissues of E. inarticulata. Remarkable ultrastructural changes in chloroplasts and nuclei of infected cells of E. inarticulata as a result of infection by M. euphorbiae were observed.     

Evaluation of neem seed powder for Fusarium wilt and Meloidogyne control on tomato

Fusarium wilt and root-knot are important diseases of tomato. The use of chemical is becoming less appealing because of the health implications. Also, the chemicals required are often not within the reach of farmers in most of the developing part of the world. This research is aimed at finding an alternative mode of control. Tomato variety Roma VF inoculated with Meloidogyne and Fusarium were treated with 2 g/kg soil neem seed powder in the screenhouse and 2 Mg ha ^{? 1} in the field. An untreated and Furadan treated plot in the field served as control. Neem seed powder significantly reduced the disease severity of Fusarium and root-knot in both screenhouse and field. Results suggest the possible use of neem seed powder for control of the root-knot nematodes - Fusarium wilt disease complex.     

Personal stigma in schizophrenia spectrum disorders: a systematic review of prevalence rates,correlates, impact and interventions

A systematic electronic PubMed, Medline and Web of Science database search was conducted regarding the prevalence, correlates, and effects of personal stigma (i.e., perceived and experienced stigmatization and self‐stigma) in patients with schizophrenia spectrum disorders. Of 54 studies (n=5,871), published from 1994 to 2011, 23 (42.6%) reported on prevalence rates, and 44 (81.5%) reported on correlates and/or consequences of perceived or experienced stigmatization or self‐stigma. Only two specific personal stigma intervention studies were found. On average, 64.5% (range: 45.0–80.0%) of patients perceived stigma, 55.9% (range: 22.5–96.0%) actually experienced stigma, and 49.2% (range: 27.9–77.0%) reported alienation (shame) as the most common aspect of self‐stigma. While socio‐demographic variables were only marginally associated with stigma, psychosocial variables, especially lower quality of life, showed overall significant correlations, and illness‐related factors showed heterogeneous associations, except for social anxiety that was unequivocally associated with personal stigma. The prevalence and impact of personal stigma on individual outcomes among schizophrenia spectrum disorder patients are well characterized, yet measures and methods differ significantly. By contrast, research regarding the evolution of personal stigma through the illness course and, particularly, specific intervention studies, which should be conducted utilizing standardized methods and outcomes, are sorely lacking.