Sporormiella as a tool for detecting the presence of large herbivores in the Neotropics

The reliability of using the abundance of Sporormiella spores as a proxy for the presence and abundance of megaherbivores was tested in southern Brazil. Mud-water interface samples from nine lakes, in which cattle-use was categorized as high, medium, or low, were assayed for Sporormiella representation. The sampling design allowed an analysis of both the influence of the number of animals using the shoreline and the distance of the sampling site from the nearest shoreline. Sporormiella was found to be a reliable proxy for the presence of large livestock. The concentration and abundance of spores declined from the edge of the lake toward the center, with the strongest response being in sites with high livestock use. Consistent with prior studies in temperate regions, we find that Sporormiella spores are a useful proxy to study the extinction of Pleistocene megafauna or the arrival of European livestock in Neotropical landscapes

siRNA against presenilin 1 (PS1) down regulates amyloid β42 production in IMR-32 cells

<p>Abstract</p> <p>Background</p> <p>One of the pathological hallmarks of Alzheimer's disease (AD) is the deposition of the ~4 kDa amyloid β protein (Aβ) within lesions known as senile plaques. Aβ is also deposited in the walls of cerebral blood vessels in many cases of AD. A substantial proportion of the Aβ that accumulates in the AD brain is deposited as Amyloid, which is highly insoluble, proteinaceous material with a β-pleated-sheet conformation and deposited extracellularly in the form of 5-10 nm wide straight fibrils. As γ-secretase catalyzes the final cleavage that releases the Aβ42 or 40 from amyloid β -protein precursor (APP), therefore, it is a potential therapeutic target for the treatment of AD. γ-Secretase cleavage is performed by a high molecular weight protein complex containing presenilins (PSs), nicastrin, Aph-1 and Pen-2. Previous studies have demonstrated that the presenilins (PS1 and PS2) are critical components of a large enzyme complex that performs γ-secretase cleavage.</p> <p>Methods</p> <p>In this study we used RNA interference (RNAi) technology to examine the effects of small-interfering RNA (siRNA) against PS1 on expression levels of PS1 and Aβ42 in IMR-32 Cells using RTPCR, western blotting and immunofluorescence techniques.</p> <p>Results</p> <p>The results of the present study showed down regulation of PS1 and Aβ42 in IMR32 cells transfected with siRNA against PS1.</p> <p>Conclusion</p> <p>Our results substantiate the concept that PS1 is involved in γ-secretase activity and provides the rationale for therapeutic strategies aimed at influencing Aβ42 production.</p

A Systematic Review of Research into the Impact of Loose Parts Play on Children's Cognitive, Social and Emotional Development

Background: Loose Parts Play (LPP) interventions introduce moveable materials and equipment to children's play spaces to facilitate unstructured, child-led play. Metaanalysis of previous school-based research has shown significant benefits of LPP for physical activity (PA). In the current paper we review the scope and quality of the quantitative evidence relating to cognitive, social, and emotional outcomes. Method: We conducted a systematic search of the literature on LPP interventions for primary school aged children which used quantitative outcome indicators for cognitive, social and/or emotional development. Studies were screened for inclusion by 2 independent researchers and reviewed for content, relevant outcomes and quality indicators. Results: Five studies met the review inclusion criteria. Two studies used a randomised controlled trial design, two studies used quasi-experimental design, and one used an observational design. Outcomes measured focused mainly on social development. With the exception of enjoyment, school satisfaction and self-esteem, emotional outcomes were almost entirely absent. No measures of cognitive or academic outcomes were found. For the studies using control groups, few differences between groups were reported, although 1 study found increased happiness at school and increased odds of reporting being pushed/shoved at playtime associated with intervention. Null results were found for peer acceptance, relational bullying, social competence, social skills, peer group size, and psychosocial quality of life. In the non-controlled study, there were observed increases in co-operative play. Conclusions: There is insufficient high-quality, quantitative, empirical evidence available to determine whether or not LPP interventions have an impact on children's cognitive, social and emotional development. We conclude our review with some recommendations which we hope will assist future research in this promising field.This study was funded by the Economic and Social Research Council (ESRC, Award Number ES/N006577/1)

Functionality of promoter microsatellites of arginine vasopressin receptor 1A (AVPR1A): implications for autism

<p>Abstract</p> <p>Background</p> <p>Arginine vasopressin (AVP) has been hypothesized to play a role in aetiology of autism based on a demonstrated involvement in the regulation of social behaviours. The arginine vasopressin receptor 1A gene (<it>AVPR1A</it>) is widely expressed in the brain and is considered to be a key receptor for regulation of social behaviour. Moreover, genetic variation at <it>AVPR1A </it>has been reported to be associated with autism. Evidence from non-human mammals implicates variation in the 5'-flanking region of <it>AVPR1A </it>in variable gene expression and social behaviour.</p> <p>Methods</p> <p>We examined four tagging single nucleotide polymorphisms (SNPs) (rs3803107, rs1042615, rs3741865, rs11174815) and three microsatellites (RS3, RS1 and AVR) at the <it>AVPR1A </it>gene for association in an autism cohort from Ireland. Two 5'-flanking region polymorphisms in the human <it>AVPR1A</it>, RS3 and RS1, were also tested for their effect on relative promoter activity.</p> <p>Results</p> <p>The short alleles of RS1 and the SNP rs11174815 show weak association with autism in the Irish population (<it>P </it>= 0.036 and <it>P </it>= 0.008, respectively). Both RS1 and RS3 showed differences in relative promoter activity by length. Shorter repeat alleles of RS1 and RS3 decreased relative promoter activity in the human neuroblastoma cell line SH-SY5Y.</p> <p>Conclusions</p> <p>These aligning results can be interpreted as a functional route for this association, namely that shorter alleles of RS1 lead to decreased <it>AVPR1A </it>transcription, which may proffer increased susceptibility to the autism phenotype.</p

Recalcitrant chronic bladder pain and recurrent cystitis but negative urinalysis - what should we do?

Purpose: Lower urinary tract symptoms (LUTS) may be associated with chronic urinary tract infection (UTI) undetected by routine diagnostic tests. Antimicrobial therapy might confer benefit for these patients. Materials and Methods: Over ten years, we treated patients with chronic LUTS. Pyuria was adopted as the principal biomarker of infection. Urinary leucocyte counts were recorded from microscopy of fresh midstream urine (MSU) samples. Antibiotics were prescribed and the prescription adjusted to achieve a measurable clinical response and a reduction in pyuria. Results: We treated 624 women (mean age=53.4 years; sd=18) with chronic LUTS and pyuria. The mean duration of symptoms prior to presentation was 6.5 years. Only 16% of MSU cultures submitted were positive (≥105 cfu ml-1). Mean treatment length was 383 days (SD=347; 95% CI=337-428). Treatment was associated with a reduction in total LUTS (F=98; p=.0001), 24-hour frequency (F=75; p=.0001), urinary 3 urgency (F=90; p=.0001), lower urinary tract pain (F=108; p=.0001), voiding symptoms (F=10; p=.002) and pyuria (F=15.4; p=.0001). Full-dose first-generation urinary antibiotic (such as cefalexin, nitrofurantoin, or trimethoprim) was combined with Methenamine Hippurate. We recorded 475 adverse events (AEs) during 273,762 treatment days. There was only one serious adverse event (SAE). We observed no increase in the proportion of resistant bacterial isolates. Conclusion: This large case series demonstrates that patients with chronic LUTS and pyuria experience symptom regression and a reduction in urinary tract inflammation associated with antimicrobial therapy. Disease regression was achieved with a low frequency of AEs. These results provide preliminary data to inform a future RCT