Frequency of the New HLA-B*2709 Allele in Ankylosing Spondylitis Patients and Healthy Individuals

We have recently described a new HLA-B27 subtype, named HLA-B*2709 (Del Porto et al. 1994). This allele is identical to the subtype most frequently found in Caucasoids, HLA-B*2705, except for a single amino acid substitution (Asp to His) in position 116. This residue, that is part of the F pocket of the molecule, has been shown to be relevant in determining which C-terminal amino acid of HLA-class I-binding peptides can be accomodated into the groove (Elliott, 1993). In nonamer peptides, this aminoacid corresponds to a primary anchor position (P9; Madden et al., 1992). Accordingly, we have previously shown that B2709 molecule hardly accepts nonamer peptides with an Arg or Tyr in P9, while the same amino acids represent good anchors for B2705 molecules (Fiorillo et al., 1995). Special attention is focused on HLA-B27 subtypes because of the strong association of B27 with ankylosing spondylitis (AS). More than 90% of AS patients are B27-positive and, conversely, about 4% of B27-positive individuals in the population are affected. This represents a relative risk over 100, that is the highest in HLA-disease associations. However, little is known on the pathogenic mechanisms of the disease. Following the hypothesis that an antigenic B27-binding peptide is involved in the disease (the so-called arthritogenic peptide), differential association with the different B27 subtypes may give a clue on the nature of such peptide. If two subtypes of partially overlapping peptide binding specificity are found to be both AS-associated, this would restrict the search for peptides that can be bound by both allelic products. Conversely, if a B27 subtype is found to be non AS-associated, this would be even more helpful in eliminating an array of peptides as possible candidates

Search strings for the study of putative occupational determinants of disease

Objective To identify efficient PubMed search strategies to retrieve articles regarding putative occupational determinants of conditions not generally considered to be work related. Methods Based on MeSH definitions and expert knowledge, we selected as candidate search terms the four MeSH terms describing 'occupational disease', 'occupational exposure', 'occupational health' and 'occupational medicine' (DEHM) alongside 22 other promising terms. We first explored overlaps between the candidate terms in PubMed. Using random samples of abstracts retrieved by each term, we estimated the proportions of articles containing potentially pertinent information regarding occupational aetiology in order to formulate two search strategies (one more 'specific', one more 'sensitive'). We applied these strategies to retrieve information on the possible occupational aetiology of meningioma, pancreatitis and atrial fibrillation. Results Only 20.3% of abstracts were retrieved by more than one DEHM term. The more 'specific' search string was based on the combination of terms that yielded the highest proportion (40%) of potentially pertinent abstracts. The more 'sensitive' string was based on the use of broader search fields and additional coverage provided by other search terms under study. Using the specific string, the numbers of abstracts needed to read to find one potentially pertinent article were 1.2 for meningioma, 1.9 for pancreatitis and 1.8 for atrial fibrillation. Using the sensitive strategy, the numbers needed to read were 4.4 for meningioma, 8.9 for pancreatitis and 10.5 for atrial fibrillation. Conclusions The proposed strings could help health care professionals explore putative occupational aetiology for diseases that are not generally thought to be work relate

Immunohistochemical and transcriptional expression of Matrix Metalloproteinases in full-term human umbilical cord and Human Umbilical Vein Endothelial Cells

Matrix metalloproteinases (MMPs) are extracellular zinc-dependent endopeptidases involved in the degradation and remodelling of extracellular matrix in physiological and pathological processes. MMPs also have a role on cell proliferation, migration, differentiation, angiogenesis and apoptosis. Umbilical cord is a special organ subjected to many changes during pre-natal life and whose cells can maintain a certain degree of plasticity also in post-natal period; for example recently they have been used as a source of stem cells. In this work we investigated the expression of MMPs in human umbilical cord and Human Umbilical Vein Endothelial Cells (HUVEC) though immunohistochemistry, RT-PCR and gelatin zymography. MMP-2 protein is expressed in the amniotic epithelium of human umbilical cord and in few sub-epithelial fibroblasts, while MMP-3 and MMP-10 only in the umbilical epithelium. MMP-8, MMP-9 and MMP-13 immunoreactivity is localised in the epithelium and in Wharton\u2019s jelly mesenchymal cells. Immunocytochemistry also revealed protein expression for MMP-2, 3, 8, 9 and 10 in cultured HUVEC. In agreement with immunohistochemical data, RT-PCR analysis performed on samples of whole umbilical cord confirmed the transcriptional expression for the genes encoding all the six matrix metalloproteinases investigated, while in HUVEC only the expression of MMP-2, 3, 9, 10 and 13 mRNAs was detected. Gelatin zymograpgy showed a clear MMP-2 and MMP-9 enzymatic activity in the conditioned medium of HUVEC at different culture passages, suggesting that HUVEC secrete gelatinases, that afterwards undergo extracellular activation, and this ability is not affected by passage number

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Decellularised skeletal muscles allow functional muscle regeneration by promoting host cell migration

Pathological conditions affecting skeletal muscle function may lead to irreversible volumetric muscle loss (VML). Therapeutic approaches involving acellular matrices represent an emerging and promising strategy to promote regeneration of skeletal muscle following injury. Here we investigated the ability of three different decellularised skeletal muscle scaffolds to support muscle regeneration in a xenogeneic immune-competent model of VML, in which the EDL muscle was surgically resected. All implanted acellular matrices, used to replace the resected muscles, were able to generate functional artificial muscles by promoting host myogenic cell migration and differentiation, as well as nervous fibres, vascular networks, and satellite cell (SC) homing. However, acellular tissue mainly composed of extracellular matrix (ECM) allowed better myofibre three-dimensional (3D) organization and the restoration of SC pool, when compared to scaffolds which also preserved muscular cytoskeletal structures. Finally, we showed that fibroblasts are indispensable to promote efficient migration and myogenesis by muscle stem cells across the scaffolds in vitro. This data strongly support the use of xenogeneic acellular muscles as device to treat VML conditions in absence of donor cell implementation, as well as in vitro model for studying cell interplay during myogenesis

Habitual Physical Activity in Mitochondrial Disease

Mitochondrial disease is the most common neuromuscular disease and has a profound impact upon daily life, disease and longevity. Exercise therapy has been shown to improve mitochondrial function in patients with mitochondrial disease. However, no information exists about the level of habitual physical activity of people with mitochondrial disease and its relationship with clinical phenotype.Habitual physical activity, genotype and clinical presentations were assessed in 100 patients with mitochondrial disease. Comparisons were made with a control group individually matched by age, gender and BMI. = −0.49; 95% CI −0.33, −0.63, P<0.01). There were no systematic differences in physical activity between different genotypes mitochondrial disease.These results demonstrate for the first time that low levels of physical activity are prominent in mitochondrial disease. Combined with a high prevalence of obesity, physical activity may constitute a significant and potentially modifiable risk factor in mitochondrial disease

Treatment with IL-7 Prevents the Decline of Circulating CD4+ T Cells during the Acute Phase of SIV Infection in Rhesus Macaques

Although treatment with interleukin-7 (IL-7) was shown to transiently expand the naïve and memory T-cell pools in patients with chronic HIV-1 infection receiving antiretroviral therapy (ART), it is uncertain whether a full immunologic reconstitution can be achieved. Moreover, the effects of IL-7 have never been evaluated during acute HIV-1 (or SIV) infection, a critical phase of the disease in which the most dramatic depletion of CD4+ T cells is believed to occur. In the present study, recombinant, fully glycosylated simian IL-7 (50 µg/kg, s.c., once weekly for 7 weeks) was administered to 6 rhesus macaques throughout the acute phase of infection with a pathogenic SIV strain (mac251); 6 animals were infected at the same time and served as untreated controls. Treatment with IL-7 did not cause clinically detectable side effects and, despite the absence of concomitant ART, did not induce significant increases in the levels of SIV replication except at the earliest time point tested (day 4 post-infection). Strikingly, animals treated with IL-7 were protected from the dramatic decline of circulating naïve and memory CD4+ T cells that occurred in untreated animals. Treatment with IL-7 induced only transient T-cell proliferation, but it was associated with sustained increase in the expression of the anti-apoptotic protein Bcl-2 on both CD4+ and CD8+ T cells, persistent expansion of all circulating CD8+ T-cell subsets, and development of earlier and stronger SIV Tat-specific T-cell responses. However, the beneficial effects of IL-7 were not sustained after treatment interruption. These data demonstrate that IL-7 administration is effective in protecting the CD4+ T-cell pool during the acute phase of SIV infection in macaques, providing a rationale for the clinical evaluation of this cytokine in patients with acute HIV-1 infection

The Gaia-ESO Survey: The inner disk, intermediate-age open cluster Trumpler 23

Milky Way open clusters are very diverse in terms of age, chemical composition, and kinematic properties. Intermediate-age and old open clusters are less common, and it is even harder to find them inside the solar Galactocentric radius, due to the high mortality rate and strong extinction inside this region. NGC 6802 is one of the inner disk open clusters (IOCs) observed by the $Gaia$-ESO survey (GES). This cluster is an important target for calibrating the abundances derived in the survey due to the kinematic and chemical homogeneity of the members in open clusters. Using the measurements from $Gaia$-ESO internal data release 4 (iDR4), we identify 95 main-sequence dwarfs as cluster members from the GIRAFFE target list, and eight giants as cluster members from the UVES target list. The dwarf cluster members have a median radial velocity of $13.6\pm1.9$ km s$^{-1}$, while the giant cluster members have a median radial velocity of $12.0\pm0.9$ km s$^{-1}$ and a median [Fe/H] of $0.10\pm0.02$ dex. The color-magnitude diagram of these cluster members suggests an age of $0.9\pm0.1$ Gyr, with $(m-M)_0=11.4$ and $E(B-V)=0.86$. We perform the first detailed chemical abundance analysis of NGC 6802, including 27 elemental species. To gain a more general picture about IOCs, the measurements of NGC 6802 are compared with those of other IOCs previously studied by GES, that is, NGC 4815, Trumpler 20, NGC 6705, and Berkeley 81. NGC 6802 shows similar C, N, Na, and Al abundances as other IOCs. These elements are compared with nucleosynthetic models as a function of cluster turn-off mass. The $\alpha$, iron-peak, and neutron-capture elements are also explored in a self-consistent way

Match running performance and physical capacity profiles of U8 and U10 soccer players

Aim This study aimed to characterize match running performance of very young soccer players and evaluate the relationship between these data and physical capacities and technical skills. Methods Distances covered at different speed thresholds were measured during 31 official matches using GPS technology in U10 (n = 12; age 10.1 ± 0.1 years) and U8 (n = 15; age 7.9 ± 0.1 years) national soccer players. Counter movement jump performance (CMJ), 20 m shuttle running (20 m-SR), linear sprint performance (10, 20, 30 m), shuttle (SHDT) and slalom dribble tests (SLDT) were performed to determine the players physical capacities and technical skills. Results Physical capacities and technical skills were higher in U10 versus U8 players [P 0.05, ES: 0.74). The U10 players covered more total (TD) and high-intensity running distance (HIRD) than their younger counterparts did (P 0.05, ES: 0.99). TD and HIRD covered across the three 15 min periods of match play did not decline (P > 0.05, ES: 0.02–0.55). Very large magnitude correlations were observed between the U8 and U10 players performances during the 20 m-SR versus TD (r = 0.79; P < 0.01) and HIRD (r = 0.82; P < 0.01) covered during match play. Conclusions Data demonstrate differences in match running performance and physical capacity between U8 and U10 players, and large magnitude relationships between match play measures and physical test performances. These findings could be useful to sports science staff working within the academies