Peripheral blood mononuclear cells represent a reservoir of bovine papillomavirus DNA in sarcoid-affected equines

Bovine papillomaviruses of types 1 and 2 (BPV-1 and -2) chiefly contribute to equine sarcoid pathogenesis. However, the mode of virus transmission and the presence of latent infections are largely unknown. This study established a PCR protocol allowing detection of E5 and L1. Subsequent screening of peripheral blood mononuclear cell (PBMC) DNA derived from horses with and without BPV-1/2-induced skin lesions demonstrated the exclusive presence of E5, but not L1, in PBMCs of BPV-1/2-infected equines. To validate this result, a blind PCR was performed from enciphered PBMC DNA derived from 66 horses, revealing E5 in the PBMCs of three individuals with confirmed sarcoids, whereas the remaining 63 sarcoid-free animals were negative for this gene. L1 could not be detected in any PBMC DNA, suggesting either deletion or interruption of this gene in PBMCs of BPV-1/-2-infected equines. These results support the hypothesis that PBMCs may serve as host cells for BPV-1/-2 DNA and contribute to virus latency.

Reactivity of human natural antibodies to endothelial cells from Galalpha(1,3)Gal-deficient pigs

BACKGROUND: Xenoreactive human natural antibodies (NAb) are predominantly directed against galactose-alpha(1,3)galactose (Gal). Binding of immunoglobulin (Ig) G and IgM NAb activates porcine endothelial cells (pEC) and triggers complement lysis responsible for hyperacute xenograft rejection. In vitro, IgG NAb induce human natural killer (NK) cell-mediated lysis of pEC by antibody-dependent cell-mediated cytotoxicity (ADCC). The present study examined the levels of anti-porcine NAb in a large number of individuals and addressed the functional role of non-Gal anti-porcine NAb. METHODS: Sera from 120 healthy human blood donors were analyzed for the presence of anti-porcine NAb by flow cytometry using porcine red blood cells (pRBC), lymphoblastoid cells (pLCL), and pEC derived from control or Gal-deficient pigs. Xenogeneic complement lysis was measured by flow cytometry using human serum and rabbit complement. ADCC was analyzed by chromium-release assays using human serum and freshly isolated NK cells. RESULTS: Human IgM binding to pRBC was found in 93% and IgG binding in 86% of all samples. Non-Gal NAb comprised 13% of total IgM and 36% of total IgG binding to pEC. NAb/complement-induced lysis and ADCC of Gal-deficient compared to Gal-positive pEC were 21% and 29%, respectively. The majority of anti-Gal and non-Gal IgG NAb were of the IgG2 subclass. CONCLUSIONS: The generation of Gal-deficient pigs has overcome hyperacute anti-Gal-mediated xenograft rejection in nonhuman primates. Non-Gal anti-porcine NAb represent a potentially relevant immunological hurdle in a subgroup of individuals by inducing endothelial damage in xenografts.

Loss of DAXX and ATRX are associated with chromosome instability and reduced survival of patients with pancreatic neuroendocrine tumors

BACKGROUND & AIMS Sporadic pancreatic neuroendocrine tumors (pNETs) are rare and genetically heterogeneous. Chromosome instability (CIN) has been detected in pNETs from patients with poor outcomes, but no specific genetic factors have been associated with CIN. Mutations in death domain-associated protein gene (DAXX) or ATR-X gene (ATRX) (which both encode proteins involved in chromatin remodeling) have been detected in 40% of pNETs, in association with activation of alternative lengthening of telomeres. We investigated whether loss of DAXX or ATRX, and consequent alternative lengthening of telomeres, are related to CIN in pNETs. We also assessed whether loss of DAXX or ATRX is associated with specific phenotypes of pNETs. METHODS We collected well-differentiated primary pNET samples from 142 patients at the University Hospital Zurich and from 101 patients at the University Hospital Bern (both located in Switzerland). Clinical follow-up data were obtained for 149 patients from general practitioners and tumor registries. The tumors were reclassified into 3 groups according to the 2010 World Health Organization classification. Samples were analyzed by immunohistochemistry and telomeric fluorescence in situ hybridization. We correlated loss of DAXX, or ATRX, expression, and activation of alternative lengthening of telomeres with data from comparative genomic hybridization array studies, as well as with clinical and pathological features of the tumors and relapse and survival data. RESULTS Loss of DAXX or ATRX protein and alternative lengthening of telomeres were associated with CIN in pNETs. Furthermore, loss of DAXX or ATRX correlated with tumor stage and metastasis, reduced time of relapse-free survival, and decreased time of tumor-associated survival. CONCLUSIONS Loss of DAXX or ATRX is associated with CIN in pNETs and shorter survival times of patients. These results support the hypothesis that DAXX- and ATRX-negative tumors are a more aggressive subtype of pNET, and could lead to identification of strategies to target CIN in pancreatic tumors.

Body salt and water balances in cardiothoracic surgery patients with intensive care unit-acquired hyponatremia

PURPOSE Hyponatremia is frequently observed in intensive care unit (ICU) patients, but there is still lack information on the physiological mechanisms of development. MATERIALS AND METHODS In this retrospective analysis we performed tonicity balances in 54 patients with ICU acquired hyponatremia. We calculated fluid and solute in and outputs during 24 hours in 106 patient days with decreasing serum-sodium levels. RESULTS We could observe a positive fluid balance as a single reason for hyponatremia in 25% of patients and a negative solute balance in 57%. In 18% both factors contributed to the decrease in serum-sodium. Hyponatremic patients had renal water retention, measured by electrolyte free water clearance calculation in 79% and positive input of free water in 67% as reasons for decline of serum-sodium. The theoretical change of serum sodium during 24 hours according to the calculations of measured balances correlated well with the real change of serum sodium (r = 0.78, P < .01). CONCLUSIONS Balance studies showed that renal water retention together with renal sodium loss and high electrolyte free water input are the major contributors to the development of hyponatremia. Control of renal water and sodium handling by urine analysis may contribute to a better fluid management in the ICU population.

Increased FOXP3 expression in tumour-associated tissues of horses affected with equine sarcoid disease.

Recent studies suggest that regulatory T cells (Tregs) are associated with disease severity and progression in papilloma virus induced neoplasia. Bovine papilloma virus (BPV) is recognised as the most important aetiological factor in equine sarcoid (ES) disease. The aim of this study was to compare expression levels of Treg markers and associated cytokines in tissue samples of ES-affected equids with skin samples of healthy control horses. Eleven ES-affected, and 12 healthy horses were included in the study. Expression levels of forkhead box protein 3 (FOXP3), interleukin 10 (IL10), interleukin 4 (IL4) and interferon gamma (IFNG) mRNA in lesional and tumour-distant samples from ES-affected horses, as well as in dermal samples of healthy control horses were measured using quantitative reverse transcription polymerase chain reaction (PCR). Expression levels were compared between lesional and tumour-distant as well as between tumour-distant and control samples. Furthermore, BPV-1 E5 DNA in samples of ES-affected horses was quantified using quantitative PCR, and possible associations of viral load, disease severity and gene expression levels were evaluated. Expression levels of FOXP3, IL10 and IFNG mRNA and BPV-1 E5 copy numbers were significantly increased in lesional compared to tumour-distant samples. There was no difference in FOXP3 and cytokine expression in tumour-distant samples from ES- compared with control horses. In tumour-distant samples viral load was positively correlated with IL10 expression and severity score. The increased expression of Treg markers in tumour-associated tissues of ES-affected equids indicates a local, Treg-induced immune suppression.

Psychological Data from an Exploration of the Rapport / Synchrony Interplay Using Motion Energy Analysis

These data result from an investigation examining the interplay between dyadic rapport and consequential behavior-mirroring. Participants responded to a variety of interpersonally-focused pretest measures prior to their engagement in videotaped interdependent tasks (coded for interactional synchrony using Motion Energy Analysis [17,18]). A post-task evaluation of rapport and other related constructs followed each exchange. Four studies shared these same dependent measures, but asked distinct questions: Study 1 (Ndyad = 38) explored the influence of perceived responsibility and gender-specificity of the task; Study 2 (Ndyad = 51) focused on dyad sex-makeup; Studies 3 (Ndyad = 41) and 4 (Ndyad = 63) examined cognitive load impacts on the interactions. Versions of the data are structured with both individual and dyad as the unit of analysis. Our data possess strong reuse potential for theorists interested in dyadic processes and are especially pertinent to questions about dyad agreement and interpersonal perception / behavior association relationships.

Effect of Combined Systemic and Local Morpholino Treatment on the Spinal Muscular Atrophy Δ7 Mouse Model Phenotype

BACKGROUND: Spinal muscular atrophy (SMA) is a fatal motor neuron disease of childhood that is caused by mutations in the SMN1 gene. Currently, no effective treatment is available. One possible therapeutic approach is the use of antisense oligos (ASOs) to redirect the splicing of the paralogous gene SMN2, thus increasing functional SMN protein production. Various ASOs with different chemical properties are suitable for these applications, including a morpholino oligomer (MO) variant with a particularly excellent safety and efficacy profile. OBJECTIVE: We investigated a 25-nt MO sequence targeting the negative intronic splicing silencer (ISS-N1) 10 to 34 region. METHODS: We administered a 25-nt MO sequence against the ISS-N1 region of SMN2 (HSMN2Ex7D[-10-34]) in the SMAΔ7 mouse model and evaluated the effect and neuropathologic phenotype. We tested different concentrations (from 2 to 24 nM) and delivery protocols (intracerebroventricular injection, systemic injection, or both). We evaluated the treatment efficacy regarding SMN levels, survival, neuromuscular phenotype, and neuropathologic features. RESULTS: We found that a 25-nt MO sequence against the ISS-N1 region of SMN2 (HSMN2Ex7D[-10-34]) exhibited superior efficacy in transgenic SMAΔ7 mice compared with previously described sequences. In our experiments, the combination of local and systemic administration of MO (bare or conjugated to octaguanidine) was the most effective approach for increasing full-length SMN expression, leading to robust improvement in neuropathologic features and survival. Moreover, we found that several small nuclear RNAs were deregulated in SMA mice and that their levels were restored by MO treatment. CONCLUSION: These results indicate that MO-mediated SMA therapy is efficacious and can result in phenotypic rescue, providing important insights for further development of ASO-based therapeutic strategies in SMA patients.

Effects of Breastfeeding on Respiratory Symptoms in Infancy.

OBJECTIVE To assess the impact of potential risk factors on the development of respiratory symptoms and their specific modification by breastfeeding in infants in the first year of life. STUDY DESIGN We prospectively studied 436 healthy term infants from the Bern-Basel Infant Lung Development cohort. The breastfeeding status, and incidence and severity of respiratory symptoms (score) were assessed weekly by telephone interview during the first year of life. Risk factors (eg, pre- and postnatal smoking exposure, mode of delivery, gestational age, maternal atopy, and number of older siblings) were obtained using standardized questionnaires. Weekly measurements of particulate matter <10 μg were provided by local monitoring stations. The associations were investigated using generalized additive mixed model with quasi Poisson distribution. RESULTS Breastfeeding reduced the incidence and severity of the respiratory symptom score mainly in the first 27 weeks of life (risk ratio 0.70; 95% CI 0.55-0.88). We found a protective effect of breastfeeding in girls but not in boys. During the first 27 weeks of life, breastfeeding attenuated the effects of maternal smoking during pregnancy, gestational age, and cesarean delivery on respiratory symptoms. There was no evidence for an interaction between breastfeeding and maternal atopy, number of older siblings, child care attendance, or particulate matter <10 μg. CONCLUSIONS This study shows the risk-specific effect of breastfeeding on respiratory symptoms in early life using the comprehensive time-series approach.

Die Entstehung des Judenthums : eine historische Untersuchung

von Eduard Meyer

Jüdische Bauern : Geschichten aus dem neuen Palästina

von S. Zemach

Das Gotteshaus : Rede gehalten zur Feier der Einweihung der neuen Synagoge zu Fulda, am 5. Diwan 5619 ; den 7. Juni 1859

von Enoch

Abundance and biomass of mesozooplankton from the Romanian littoral during DANUBS_2002 in spring and autumn 2002

The Danubs 2002 dataset contains zooplankton data collected in April, June,September and October 2002 in 11 station allong 5 transect in front of the Romanian littoral. Zooplankton sampling was undertaken at 11 stations where samples were collected using a Juday closing net in the 0-10, 10-25, and 25-50m layer (depending also on the water masses). The dataset includes samples analysed for mesozooplankton species composition and abundance. Sampling volume was estimated by multiplying the mouth area with the wire length. Taxon-specific mesozooplankton abundance was count under microscope. Total abundance is the sum of the counted individuals. Total biomass Fodder, Rotifera , Ctenophora and Noctiluca was estimated using a tabel with wet weight for each species an stage.