BCL10 is rarely mutated in human prostate carcinoma, small-cell lung cancer, head and neck tumours, renal carcinoma and sarcomas

We have used single-strand conformation polymorphism (SSCP) analysis to screen for mutations in the BCL 10 gene in 81 primary prostate carcinomas, 20 squamous cell cancers of the head and neck, 15 small-cell lung cancer cell lines, 24 renal carcinoma cell lines and 13 sarcoma cell lines. We failed to find evidence of somatically acquired mutations of the BCL10 gene suggesting that BCL 10 does not play a major role in the development of these malignancies

Demographic and reproductive associations with nematode infection in a long-lived mammal

Infection by macroparasites, such as nematodes, varies within vertebrate host systems; elevated infection is commonly observed in juveniles and males, and, for females, with different reproductive states. However, while such patterns are widely recognized in short-lived model systems, how they apply to long-lived hosts is comparatively understudied. Here, we investigated how infection varies with host age, sex, and female reproduction in a semi-captive population of individually marked Asian elephants Elephas maximus. We carried out 1,977 faecal egg counts (FECs) across five years to estimate nematode loads for 324 hosts. Infection patterns followed an established age-infection curve, whereby calves (5 years) exhibited the highest FECs and adults (45 years) the lowest. However, males and females had similar FECs across their long lifespan, despite distinct differences in life-history strategy and clear sexual dimorphism. Additionally, although mothers invest two years in pregnancy and a further three to five years into lactation, nematode load did not vary with four different measures of female reproduction. Our results provide a much-needed insight into the host-parasite dynamics of a long-lived host; determining host-specific associations with infection in such systems is important for broadening our knowledge of parasite ecology and provides practical applications for wildlife medicine and management

Clinical relevance of genetic instability in prostatic cells obtained by prostatic massage in early prostate cancer

We investigated whether genetic lesions such as loss of heterozygosity (LOH) are detected in prostatic cells obtained by prostatic massage during early diagnosis of prostate cancer (CaP) and discussed their clinical relevance. Blood and first urine voided after prostatic massage were collected in 99 patients with total prostate-specific antigen (PSA) between 4 and 10 ng ml−1, prior to prostate biopsies. Presence of prostatic cells was confirmed by quantitative RT–PCR analysis of PSA mRNA. Genomic DNA was analysed for LOH on six chromosomal regions. One or more allelic deletions were found in prostatic fluid from 57 patients analysed, of whom 33 (58%) had CaP. Sensitivity and specificity of LOH detection and PSA free to total ratio <15% for positive biopsy were respectively 86.7 and 44% (P=0.002) for LOH, and 55 and 74% (P=0.006) for PSA ratio <15%. Analysis of LOH obtained from prostatic tumours revealed similar patterns compared to prostatic fluid cells in 86% of cases, confirming its accuracy. The presence of LOH of urinary prostatic cells obtained after prostatic massage is significantly associated with CaP on biopsy and may potentially help to identify a set of patients who are candidates for further prostate biopsies

Variable, but not free-weight, resistance back squat exercise potentiates jump performance following a comprehensive task-specific warm-up

Studies examining acute, high-speed movement performance enhancement following intense muscular contractions (frequently called "post-activation potentiation"; PAP) often impose a limited warm-up, compromizing external validity. In the present study, the effects on countermovement vertical jump (CMJ) performance of back squat exercises performed with or without elastic bands during warm-up were compared. After familiarization, fifteen active men visited the laboratory on two occasions under randomized, counterbalanced experimental squat warm-up conditions: (a) free-weight resistance (FWR) and (b) variable resistance (VR). After completing a comprehensive task-specific warm-up, three maximal CMJs were performed followed by three back squat repetitions completed at 85% of 1-RM using either FWR or VR Three CMJs were then performed 30 seconds, 4 minutes, 8 minutes, and 12 minutes later. During CMJ trials, hip, knee, and ankle joint kinematics, ground reaction force data and vastus medialis, vastus lateralis, and gluteus maximus electromyograms (EMG) were recorded simultaneously using 3D motion analysis, force platform, and EMG techniques, respectively. No change in any variable occurred after FWR (P > 0.05). Significant increases (P < 0.05) were detected at all time points following VR in CMJ height (5.3%-6.5%), peak power (4.4%-5.9%), rate of force development (12.9%-19.1%), peak concentric knee angular velocity (3.1%-4.1%), and mean concentric vastus lateralis EMG activity (27.5%-33.4%). The lack of effect of the free-weight conditioning contractions suggests that the comprehensive task-specific warm-up routine mitigated any further performance augmentation. However, the improved CMJ performance following the use of elastic bands is indicative that specific alterations in force-time properties of warm-up exercises may further improve performance

Targeted high throughput sequencing in clinical cancer Settings: formaldehyde fixed-paraffin embedded (FFPE) tumor tissues, input amount and tumor heterogeneity

<p>Abstract</p> <p>Background</p> <p>Massively parallel sequencing technologies have brought an enormous increase in sequencing throughput. However, these technologies need to be further improved with regard to reproducibility and applicability to clinical samples and settings.</p> <p>Methods</p> <p>Using identification of genetic variations in prostate cancer as an example we address three crucial challenges in the field of targeted re-sequencing: Small nucleotide variation (SNV) detection in samples of formalin-fixed paraffin embedded (FFPE) tissue material, minimal amount of input sample and sampling in view of tissue heterogeneity.</p> <p>Results</p> <p>We show that FFPE tissue material can supplement for fresh frozen tissues for the detection of SNVs and that solution-based enrichment experiments can be accomplished with small amounts of DNA with only minimal effects on enrichment uniformity and data variance.</p> <p>Finally, we address the question whether the heterogeneity of a tumor is reflected by different genetic alterations, e.g. different foci of a tumor display different genomic patterns. We show that the tumor heterogeneity plays an important role for the detection of copy number variations.</p> <p>Conclusions</p> <p>The application of high throughput sequencing technologies in cancer genomics opens up a new dimension for the identification of disease mechanisms. In particular the ability to use small amounts of FFPE samples available from surgical tumor resections and histopathological examinations facilitates the collection of precious tissue materials. However, care needs to be taken in regard to the locations of the biopsies, which can have an influence on the prediction of copy number variations. Bearing these technological challenges in mind will significantly improve many large-scale sequencing studies and will - in the long term - result in a more reliable prediction of individual cancer therapies.</p

Monoclonal Antibodies against Accumulation-Associated Protein Affect EPS Biosynthesis and Enhance Bacterial Accumulation of Staphylococcus epidermidis

Because there is no effective antibiotic to eradicate Staphylococcus epidermidis biofilm infections that lead to the failure of medical device implantations, the development of anti-biofilm vaccines is necessary. Biofilm formation by S. epidermidis requires accumulation-associated protein (Aap) that contains sequence repeats known as G5 domains, which are responsible for the Zn2+-dependent dimerization of Aap to mediate intercellular adhesion. Antibodies against Aap have been reported to inhibit biofilm accumulation. In the present study, three monoclonal antibodies (MAbs) against the Aap C-terminal single B-repeat construct followed by the 79-aa half repeat (AapBrpt1.5) were generated. MAb18B6 inhibited biofilm formation by S. epidermidis RP62A to 60% of the maximum, while MAb25C11 and MAb20B9 enhanced biofilm accumulation. All three MAbs aggregated the planktonic bacteria to form visible cell clusters. Epitope mapping revealed that the epitope of MAb18B6, which recognizes an identical area within AapBrpt constructs from S. epidermidis RP62A, was not shared by MAb25C11 and MAb20B9. Furthermore, all three MAbs were found to affect both Aap expression and extracellular polymeric substance (EPS, including extracellular DNA and PIA) biosynthesis in S. epidermidis and enhance the cell accumulation. These findings contribute to a better understanding of staphylococcal biofilm formation and will help to develop epitope-peptide vaccines against staphylococcal infections

Autism Symptoms and Internalizing Psychopathology in Girls and Boys with Autism Spectrum Disorders

Findings regarding phenotypic differences between boys and girls with ASD are mixed. We compared autism and internalizing symptoms in a sample of 8-18 year-old girls (n = 20) and boys (n = 20) with ASD and typically developing (TYP) girls (n = 19) and boys (n = 17). Girls with ASD were more impaired than TYP girls but did not differ from boys with ASD in autism symptoms. In adolescence, girls with ASD had higher internalizing symptoms than boys with ASD and TYP girls, and higher symptoms of depression than TYP girls. Girls ages 8-18 with ASD resemble boys with ASD and not TYP girls, and appear to be at increased risk for affective symptoms in the teen years

Interactions between Spider Silk and Cells – NIH/3T3 Fibroblasts Seeded on Miniature Weaving Frames

Native spider silk does not require any modification to its application as a biomaterial that can rival any artificial material in terms of cell growth promoting properties. We could show adhesion mechanics on intracellular level. Additionally, proliferation kinetics were higher than in enzymatically digested controls, indicating that spider silk does not require modification. Recent findings concerning reduction of cell proliferation after exposure could not be met. As biotechnological production of the hierarchical composition of native spider silk fibres is still a challenge, our study has a pioneer role in researching cellular mechanics on native spider silk fibres

Smaller spared subcortical nuclei are associated with worse post-stroke sensorimotor outcomes in 28 cohorts worldwide

Up to two-thirds of stroke survivors experience persistent sensorimotor impairments. Recovery relies on the integrity of spared brain areas to compensate for damaged tissue. Deep grey matter structures play a critical role in the control and regulation of sensorimotor circuits. The goal of this work is to identify associations between volumes of spared subcortical nuclei and sensorimotor behaviour at different timepoints after stroke. We pooled high-resolution T1-weighted MRI brain scans and behavioural data in 828 individuals with unilateral stroke from 28 cohorts worldwide. Cross-sectional analyses using linear mixed-effects models related post-stroke sensorimotor behaviour to non-lesioned subcortical volumes (Bonferroni-corrected, P < 0.004). We tested subacute (≤90 days) and chronic (≥180 days) stroke subgroups separately, with exploratory analyses in early stroke (≤21 days) and across all time. Sub-analyses in chronic stroke were also performed based on class of sensorimotor deficits (impairment, activity limitations) and side of lesioned hemisphere. Worse sensorimotor behaviour was associated with a smaller ipsilesional thalamic volume in both early (n = 179; d = 0.68) and subacute (n = 274, d = 0.46) stroke. In chronic stroke (n = 404), worse sensorimotor behaviour was associated with smaller ipsilesional putamen (d = 0.52) and nucleus accumbens (d = 0.39) volumes, and a larger ipsilesional lateral ventricle (d = -0.42). Worse chronic sensorimotor impairment specifically (measured by the Fugl-Meyer Assessment; n = 256) was associated with smaller ipsilesional putamen (d = 0.72) and larger lateral ventricle (d = -0.41) volumes, while several measures of activity limitations (n = 116) showed no significant relationships. In the full cohort across all time (n = 828), sensorimotor behaviour was associated with the volumes of the ipsilesional nucleus accumbens (d = 0.23), putamen (d = 0.33), thalamus (d = 0.33) and lateral ventricle (d = -0.23). We demonstrate significant relationships between post-stroke sensorimotor behaviour and reduced volumes of deep grey matter structures that were spared by stroke, which differ by time and class of sensorimotor measure. These findings provide additional insight into how different cortico-thalamo-striatal circuits support post-stroke sensorimotor outcomes

Injury rates and injury risk factors among federal bureau of investigation new agent trainees

<p>Abstract</p> <p>Background</p> <p>A one-year prospective examination of injury rates and injury risk factors was conducted in Federal Bureau of Investigation (FBI) new agent training.</p> <p>Methods</p> <p>Injury incidents were obtained from medical records and injury compensation forms. Potential injury risk factors were acquired from a lifestyle questionnaire and existing data at the FBI Academy.</p> <p>Results</p> <p>A total of 426 men and 105 women participated in the project. Thirty-five percent of men and 42% of women experienced one or more injuries during training. The injury incidence rate was 2.5 and 3.2 injuries/1,000 person-days for men and women, respectively (risk ratio (women/men) = 1.3, 95% confidence interval = 0.9-1.7). The activities most commonly associated with injuries (% of total) were defensive tactics training (58%), physical fitness training (20%), physical fitness testing (5%), and firearms training (3%). Among the men, higher injury risk was associated with older age, slower 300-meter sprint time, slower 1.5-mile run time, lower total points on the physical fitness test (PFT), lower self-rated physical activity, lower frequency of aerobic exercise, a prior upper or lower limb injury, and prior foot or knee pain that limited activity. Among the women higher injury risk was associated with slower 300-meter sprint time, slower 1.5-mile run time, lower total points on the PFT, and prior back pain that limited activity.</p> <p>Conclusion</p> <p>The results of this investigation supported those of a previous retrospective investigation emphasizing that lower fitness and self-reported pain limiting activity were associated with higher injury risk among FBI new agents.</p