Cyclic stretch increases splicing noise rate in cultured human fibroblasts

BACKGROUND: Mechanical forces are known to alter the expression of genes, but it has so far not been reported whether they may influence the fidelity of nucleus-based processes. One experimental approach permitting to address this question is the application of cyclic stretch to cultured human fibroblasts. As a marker for the precision of nucleus-based processes, the number of errors that occur during co-transcriptional splicing can then be measured. This so-called splicing noise is found at low frequency in pre-mRNA splicing. FINDINGS: The amount of splicing noise was measured by RT-qPCR of seven exon skips from the test genes AATF, MAP3K11, NF1, PCGF2, POLR2A and RABAC1. In cells treated by altered uniaxial cyclic stretching for 18 h, a uniform and significant increase of splicing noise was found for all detectable exon skips. CONCLUSION: Our data demonstrate that application of cyclic stretch to cultured fibroblasts correlates with a reduced transcriptional fidelity caused by increasing splicing noise

Impact of delay in early swallow screening on pneumonia, length of stay in hospital, disability and mortality in acute stroke patients

Background/Objectives: Early swallow screening, within 4 h of admission, is required for all acute stroke patients to commence nutritional support, as recommended. We evaluated the impact of delay in early swallow screening on outcomes in patients admitted with acute stroke. Subjects/Methods: Prospective cohort study of 1656 men (mean ± SD age = 73.1y ± 13.2) and 1653 women (79.3y ± 13.0) admitted with stroke to hyperacute stroke units (HASUs) in Surrey. Logistic regression was used to assess the risk (adjusted for age, stroke severity and co-morbidities) of delay in swallow screening on pneumonia, length of stay (LOS) > 3 weeks in HASU or hospital, moderately severe to severe disability on discharge (modified Rankin scale score = 4–5) and mortality during admission. Results: Compared with those who received swallow screening within 4 h of admission, a delay between 4 and 72 h was associated with greater risks of pneumonia: OR = 1.4 (95%CI:1.1–1.9, P = 0.022), moderately severe to severe disability on discharge: OR = 1.4 (1.1–1.7, P = 0.007) and a delay beyond 72 h was associated with even greater risks of pneumonia: OR = 2.3 (1.4–3.6, P < 0.001), prolonged LOS in HASU: OR = 1.7 (1.0–3.0, P = 0.047, median LOS = 6.2 vs. 14.7 days) and hospital: OR = 2.1-fold (1.3–3.4, P = 0.007, median LOS = 6.8 vs. 14.9 days), moderately severe to severe disability on discharge: OR = 2.5 (1.7–3.7, P < 0.001) and mortality: OR = 3.8 (2.5–5.6, P < 0.001). These risks persisted after excluding 103 patients who died within 72 h. Conclusions: Delay in early screening for swallow capacity in acute stroke patients is detrimental to outcomes, possibly due to delaying nutritional provision or through inappropriate feeding leading to aspiration. Routine early screening needs greater attention in HASUs

Microfluidics: reframing biological enquiry

The underlying physical properties of microfluidic tools have led to new biological insights through the development of microsystems that can manipulate, mimic and measure biology at a resolution that has not been possible with macroscale tools. Microsystems readily handle sub-microlitre volumes, precisely route predictable laminar fluid flows and match both perturbations and measurements to the length scales and timescales of biological systems. The advent of fabrication techniques that do not require highly specialized engineering facilities is fuelling the broad dissemination of microfluidic systems and their adaptation to specific biological questions. We describe how our understanding of molecular and cell biology is being and will continue to be advanced by precision microfluidic approaches and posit that microfluidic tools - in conjunction with advanced imaging, bioinformatics and molecular biology approaches - will transform biology into a precision science

A large displacement, high frequency, underwater microelectromechanical systems actuator

Here, we demonstrate an in situ electrostatic actuator that can operate underwater across a wide range of displacements and frequencies, achieving a displacement of approximately 10-μm at 500-Hz and 1-μm at 5-kHz; this performance surpasses that of existing underwater physical actuators. To attain these large displacements at such high speeds, we optimized critical design parameters using a computationally efficient description of the physics of low quality (Q) factor underwater electrostatic actuators. Our theoretical model accurately predicts actuator motion profiles as well as limits of bandwidth and displacement

The kitchen as a physics classroom

Cooking is a tangible, familiar, and delicious tool for teaching physics, which is easy to implement in a university setting. Through our courses at Harvard and UCLA, each year we are engaging hundreds of undergraduate students, primarily non-science majors, in science concepts and the scientific research process. We find that weekly lectures by chefs and professors, paired with edible lab experiments, generate enthusiasm and provide strong motivation for students to learn physics. By the end of the course, students are able to conduct independent scientific research and present their results in a final science fair. Given the considerable broad appeal of food and cooking, the topic could be adapted to other post-secondary as well as secondary-level courses

Designer emulsions using microfluidics

We describe new developments for the controlled fabrication of monodisperse emulsions using microfluidics. We use glass capillary devices to generate single, double, and higher order emulsions with exceptional precision. These emulsions can serve as ideal templates for generating well-defined particles and functional vesicles. Polydimethylsiloxane microfluidic devices are also used to generate picoliter-scale water-in-oil emulsions at rates as high as 10 000 drops per second. These emulsions have great potential as individual microvessels in high-throughput screening applications, where each drop serves to encapsulate single cells, genes, or reactants. © 2008 Elsevier Ltd. All rights reserved.link_to_subscribed_fulltex

Whale Shark (Rhincodon typus) Seasonal Presence, Residence Time and Habitat Use at Darwin Island, Galapagos Marine Reserve

The life history of the whale shark (Rhincodon typus), including its reproductive ecology, still remains largely unknown. Here, we present results from the first whale shark population study around Darwin Island, Galapagos Marine Reserve. Following a diversified approach we characterized seasonal occurrence, population structure and size, and described habitat use of whale sharks based on fine scale movements around the island. Whale shark presence at Darwin Island was negatively correlated with Sea Surface Temperature (SST), with highest abundance corresponding to a cool season between July and December over six years of monitoring. From 2011 to 2013 we photo-identified 82 whale sharks ranging from 4 to 13.1 m Total Length (TL). Size distribution was bimodal, with a great majority (91.5%) of adult female individuals averaging 11.35 m±0.12 m (TL±SE), all but one showing signs of a potential pregnancy. Population dynamics models for apparently pregnant sharks estimated the presence of 3.76±0.90 (mean ± SE) sharks in the study area per day with an individual residence time of 2.09±0.51 (mean ± SE) days. Movement patterns analysis of four apparently pregnant individuals tracked with acoustic tags at Darwin Island revealed an intense use of Darwin's Arch, where no feeding or specific behavior has been recorded, together with periodic excursions around the island's vicinity. Sharks showed a preference for intermediate depths (20-30 m) with occasional dives mostly to mid-water, remaining the majority of their time at water temperatures between 24-25°C. All of our results point to Darwin Island as an important stopover in a migration, possibly with reproductive purposes, rather than an aggregation site. Current studies carried out in this area to investigate regional scale movement patterns may provide essential information about possible pupping grounds for this enigmatic species