Activity

Epithelial sheets define organ architecture during development. selleck compound Here, we employed an iterative multiscale computational modeling and quantitative experimental approach to decouple direct and indirect effects of actomyosin-generated forces, nuclear positioning, extracellular matrix, and cell-cell adhesion in shaping Drosophila wing imaginal discs. Basally generated actomyosin forces generate epithelial bending of the wing disc pouch. Surprisingly, acute pharmacological inhibition of ROCK-driven actomyosin contractility does not impact the maintenance of tissue height or curved shape. Computational simulations show that ECM tautness provides only a minor contribution to modulating tissue shape. Instead, passive ECM pre-strain serves to maintain the shape independent from actomyosin contractility. These results provide general insight into how the subcellular forces are generated and maintained within individual cells to induce tissue curvature. Thus, the results suggest an important design principle of separable contributions from ECM prestrain and actomyosin tension during epithelial organogenesis and homeostasis.

In this paper, we aim to detail the setup of a high spatio-temporal resolution, electrical recording system utilising planar microelectrode arrays with simultaneous optical imaging suitable for evaluating microelectrode performance with a proposed ‘performance factor’ metric.

Techniques that would facilitate low noise electrical recordings were coupled with voltage sensitive dyes and neuronal activity was recorded both electrically via a customised amplification system and optically via a high speed CMOS camera. This technique was applied to characterise microelectrode recording performance of gold and poly(3,4-ethylenedioxythiophene)/polystyrene sulfonate (PEDOT/PSS) coated electrodes through traditional signal to noise (SNR) calculations as well as the proposed performance factor.

Neuronal activity was simultaneously recorded using both electrical and optical techniques and this activity was confirmed via tetrodotoxin application to inhibit action potential firing. PEDOT/PSS outperformed gold using both measurements, however, the performance factor metric estimated a 3 fold improvement in signal transduction when compared to gold, whereas SNR estimated an 8 fold improvement when compared to gold.

The design and functionality of a system to record from neurons both electrically, through microelectrode arrays, and optically via voltage sensitive dyes was successfully achieved.

The high spatiotemporal resolution of both electrical and optical methods will allow for an array of applications such as improved detection of subthreshold synaptic events, validation of spike sorting algorithms and a provides a robust evaluation of extracellular microelectrode performance.

The high spatiotemporal resolution of both electrical and optical methods will allow for an array of applications such as improved detection of subthreshold synaptic events, validation of spike sorting algorithms and a provides a robust evaluation of extracellular microelectrode performance.The effects of High-Intensity Functional Training (HIFT) on body composition and the relationship of the latter with performance are not well defined. In this work we investigated, by means of Dual-energy X-ray Absorptiometry, the relative proportions of fat-, lean soft tissue-, and mineral mass in CrossFit® (CF, a popular mode of HIFT) participants (n = 24; age, 28.2 ± 3.39 y; BMI, 25.3 ± 2.04 kg/m2) with at least 1 year of CF training experience and weekly amount of training > 10 h/w (n = 13; Higher Training, HT) or less then 10 h/w (n = 11; Lower Training, LT) as well as age- matched and BMI-matched physically active controls (CHT, CLT). Performance was assessed in the “Fran” workout. Data were analyzed by one-way or repeated measures ANOVA where needed. Association between variables was assessed with the Pearson’s correlation coefficient r. Partial correlation was used where needed. Results showed that HT performed better than LT in the “Fran” (P less then 0.001) and they had higher whole-body bone mineral density (P = 0.026) and higher lean soft mass (P = 0.002), and borderline lower percent fat mass (P = 0.050). The main difference between CF participants (HT, LT) and their respective controls (CHT, CLT) was a lower adiposity in the former. In CF participants, performance positively correlated with appendicular lean soft tissue mass (P = 0.030). It can be concluded that, in CF participants, a higher amount of weekly training improves most notably lean body mass and increases performance in association with increased skeletal muscle mass. CF participation is especially effective in reducing fat mass vs. age- and BMI-matched physically active controls.Although dysregulation of mitochondrial dynamics has been linked to cellular senescence, which contributes to advanced age-related disorders, it is unclear how Krüppel-like factor 5 (Klf5), an essential transcriptional factor of cardiovascular remodeling, mediates the link between mitochondrial dynamics and vascular smooth muscle cell (VSMC) senescence. Here, we show that Klf5 down-regulation in VSMCs is correlated with rupture of abdominal aortic aneurysm (AAA), an age-related vascular disease. Mice lacking Klf5 in VSMCs exacerbate vascular senescence and progression of angiotensin II (Ang II)-induced AAA by facilitating reactive oxygen species (ROS) formation. Klf5 knockdown enhances, while Klf5 overexpression suppresses mitochondrial fission. Mechanistically, Klf5 activates eukaryotic translation initiation factor 5a (eIF5a) transcription through binding to the promoter of eIF5a, which in turn preserves mitochondrial integrity by interacting with mitofusin 1 (Mfn1). Accordingly, decreased expression of eIF5a elicited by Klf5 down-regulation leads to mitochondrial fission and excessive ROS production. Inhibition of mitochondrial fission decreases ROS production and VSMC senescence. Our studies provide a potential therapeutic target for age-related vascular disorders.

Treatment needs for Schistosoma haematobium are commonly evaluated using urine filtration with detection of parasite eggs under a microscope. A common symptom of S. haematobium is hematuria, the passing of blood in urine. Hence, the use of hematuria-based diagnostic techniques as a proxy for the assessment of treatment needs has been considered. This study evaluates data from a national survey in Zimbabwe, where three hematuria-based diagnostic techniques, that is microhematuria, macrohematuria, and an anamnestic questionnaire pertaining to self-reported blood in urine, have been included in addition to urine filtration in 280 schools across 70 districts.

We developed an egg count model, which evaluates the infection intensity-dependent sensitivity and the specificity of each diagnostic technique without relying on a ‘gold’ standard. Subsequently, we determined prevalence thresholds for each diagnostic technique, equivalent to a 10% urine filtration-based prevalence and compared classification of districts according to treatment strategy based on the different diagnostic methods.