Notes

The mechanism of gap generation by way of a multi purpose nuclease through starting excision restore.
Formins generate unbranched actin filaments by a conserved, processive actin assembly mechanism. Most organisms express multiple formin isoforms that mediate distinct cellular processes and facilitate actin filament polymerization by significantly different rates, but how these actin assembly differences correlate to cellular activity is unclear. Galunisertib We used a computational model of fission yeast cytokinetic ring assembly to test the hypothesis that particular actin assembly properties help tailor formins for specific cellular roles. Simulations run in different actin filament nucleation and elongation conditions revealed that variations in formin's nucleation efficiency critically impact both the probability and timing of contractile ring formation. To probe the physiological importance of nucleation efficiency, we engineered fission yeast formin chimera strains in which the FH1-FH2 actin assembly domains of full-length cytokinesis formin Cdc12 were replaced with the FH1-FH2 domains from functionally and evolutionarily diverse formins with significantly different actin assembly properties. Although Cdc12 chimeras generally support life in fission yeast, quantitative live-cell imaging revealed a range of cytokinesis defects from mild to severe. In agreement with the computational model, chimeras whose nucleation efficiencies are least similar to Cdc12 exhibit more severe cytokinesis defects, specifically in the rate of contractile ring assembly. Together, our computational and experimental results suggest that fission yeast cytokinesis is ideally mediated by a formin with properly tailored actin assembly parameters.A "permanent" bent shape can be imposed on a straight human hair by a two-stage reduction/oxidation (perm-waving) process. The process relies on the molecular level on sulfhydryl/disulfide interchange as bond exchange reaction (BER). We expected a well-documented transition temperature around 60°C to be the trigger for the shape memory (SM) process of perm-waved hair. We confirm the existence of the SM process as such and investigate its time and temperature dependence. The results show a two-stage SM behavior, implying two distinct variations of the BER. The model to fit the data contains two fractional, normalized, elastic bending rigidities, which are strictly compensatory. They show Arrhenius-type temperature dependence and a common activation energy (EA) of ∼-12 kJ/mol. The characteristic relaxation time for the first SM process shows little, if any, temperature dependence (EA = -4 ± 2.7 kJ/mol). This is in contrast to the second process (EA = -58 ± 5.5 kJ/mol) but in line with the expected properties of the suggested BERs. None of the parameters shows any sign of the expected trigger transition (∼60°C). We hypothesize that this specific transition occurs only for large tensile deformations, when specific SS bonds in the intermediate filaments of hair are activated. There is thus no specific "trigger" transition for the SM behavior of bent, perm-waved hair.A hallmark feature of lens development and differentiation is the complete elimination of organelles from the center of the eye lens. A long unanswered question in lens biology is what are the mechanisms that control the elimination of organelles during the terminal remodeling program to form mature lens fiber cells? Recent advances have expanded our understanding of these mechanisms including newly discovered signaling pathways, proteasomal regulators, autophagy proteins, transcription factors and the hypoxic environment of the lens itself. These recent discoveries suggest that distinct mechanisms coordinate the elimination of the nucleus, mitochondria, endoplasmic reticulum and Golgi apparatus during lens fiber cell differentiation. Since regulation of organelle number and distribution is also a feature of the terminal remodeling programs of more complex cell-types and tissues, these advances are likely to impact a wide-variety of fields.A primigravida at 32 weeks of gestation presented to us with eclampsia and Posterior Reversible Encephalopathy Syndrome (PRES) along with SARS COVID-19 pneumonia. Immediate termination of pregnancy was done under general anesthesia and patient was electively ventilated in view of increased oxygen requirements. Further therapy using magnesium sulphate, antihypertensives, steroids, and convalescent plasma was carried out. The condition of the patient steadily improved leading to her extubation on the 4th postoperative day and subsequent discharge on the 8th day of admission.
Dexmedetomidine is a potent adrenergic alpha-2 agonist, and analgesic, sedative, anxiolytic and sympatholytic. Given there have been reports of dexmedetomidine associated temperature changes, in which these events have been associated with complications, our objective was to describe both temperature increase and decrease, during the intra and postoperative period (initial 24hours), and factors associated, in patients who received dexmedetomidine for anesthesia/sedation in the surgical suite.

Retrospective observational study, analyzing charts of patients ≥ 18 years submitted to anesthesia/sedation with dexmedetomidine, between 1/1/2017 and 31/12/2017. Upper temperature threshold was considered ≥ 37.8°C, and lower, < 35°C. The association with dexmedetomidine was assessed by the OMS/UMC causality system and by the Naranjo algorithm.

The sample included 42 patients who received dexmedetomidine and whose temperature data were available, with predominance of men 26 (62%), 49.4/16.5 years old (mean/standard deviation), and weight 65/35.8kg. None of the patients presented intraoperative temperature equal to or above 37.8°C or below 35°C. During the postoperative period, one patient presented an increase ≥ 37.8°C (2.4%) and three, temperature decrease < 35°C (7%). Surgery/anesthesia time and exposure time to dexmedetomidine were not appropriate linear predictors of maximum temperature. Older age (p<0.01), longer exposure to dexmedetomidine (p<0.05) and shorter surgery time (p<0.01) were significant linear predictors for lower minimum temperature.

Increase ≥ 37.8°C/decrease < 35°C of temperature possibly associated with dexmedetomidine did not occur in the intraoperative period and had a low frequency during the postoperative period.
Increase ≥ 37.8 °C/decrease less then 35 °C of temperature possibly associated with dexmedetomidine did not occur in the intraoperative period and had a low frequency during the postoperative period.
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