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This study is the first to show the differential effect of patient 5'-phosphatase mutations on cellular phenotypes and introduces a conformational disease component in LS. This work provides a framework that explains symptom heterogeneity and can help stratify patients as well as to produce a more accurate prognosis depending on the nature and location of the mutation within the OCRL1 gene.Polyploidy can provide adaptive advantages and drive evolution. Amitotic division of the polyploid macronucleus (MAC) in ciliates acts as a nonsexual genetic mechanism to enhance adaptation to stress conditions and thus provides a unique model to investigate the evolutionary role of polyploidy. Mutation is the primary source of the variation responsible for evolution and adaptation; however, to date, de novo mutations that occur in ciliate MAC genomes during these processes have not been characterized and their biological impacts are undefined. Here, we carried out long-term evolution experiments to directly explore de novo MAC mutations and their molecular features in the model ciliate, Tetrahymena thermophila. A simple but effective method was established to detect base-substitution mutations in evolving populations whereas filtering out most of the false positive base-substitutions caused by repetitive sequences and the programmed genome rearrangements. The detected mutations were rigorously validated using the MassARRAY system. Validated mutations showed a strong G/C→A/T bias, consistent with observations in other species. Moreover, a progressive increase in growth rate of the evolving populations suggested that some of these mutations might be responsible for cell fitness. The established mutation identification and validation methods will be an invaluable resource to make ciliates an important model system to study the role of polyploidy in evolution.

increases in arterial pressure (AP) during sleep and smaller differences in AP between sleep and wakefulness have been reported in orexin (hypocretin)-deficient mouse models of narcolepsy type 1 (NT1) and confirmed in NT1 patients. We tested whether these alterations are mediated by parasympathetic or sympathetic control of the heart and/or resistance vessels in an orexin-deficient mouse model of NT1.

13 orexin knock-out (ORX-KO) mice were compared with 12 congenic wild-type (WT) mice. The electroencephalogram, electromyogram, and AP of the mice were recorded in the light (rest) period during intraperitoneal infusion of atropine methyl nitrate, atenolol, or prazosin to block muscarinic cholinergic, β1-adrenergic, or α1-adrenergic receptors, respectively, while saline was infused as control.

AP significantly depended on a 3-way interaction among the mouse group (ORX-KO vs WT), the wake-sleep state, and the drug or vehicle infused. During the control vehicle infusion, ORX-KO had significantly higher AP values during REM sleep, smaller decreases in AP from wakefulness to either non-rapid-eye-movement (non-REM) sleep or REM sleep, and greater increases in AP from non-REM sleep to REM sleep compared to WT. These differences remained significant with atropine methyl nitrate, whereas they were abolished by prazosin and, except for the smaller AP decrease from wakefulness to REM sleep in ORX-KO, also by atenolol.

sleep-related alterations of AP due to orexin deficiency significantly depend on alterations in cardiovascular sympathetic control in a mouse model of NT1.

sleep-related alterations of AP due to orexin deficiency significantly depend on alterations in cardiovascular sympathetic control in a mouse model of NT1.

On March 10, 2020, the Italian Government ordered a national lockdown to limit the viral transmission of coronavirus disease 2019 infections. This study investigated how these restrictive measures have impacted sleep quality, timing, and psychological difficulties in school-age children and their mothers during the lockdown.

In an online survey, 299 mothers reported their sleep habits, experience of time, and psychological difficulties as well as those of their children (6-10 years old) during and, retrospectively, before the lockdown.

During the lockdown, children showed a marked delay in sleep timing-that is, later bedtime and rise time-and a mild worsening in sleep quality. They were less prone to respect daily routines or to keep track of the passage of time. They showed increased emotional, conduct, and hyperactive symptoms, and the increase in these psychological difficulties was predicted by the change in sleep quality, boredom, and mothers' psychological difficulties. In addition, mothers showed a delayed sleep timing and worsening of sleep quality during the lockdown, in varying degrees depending on their working conditions. Mothers who kept working regularly outside their homes during lockdown reported more regular sleep patterns, whereas mothers who stopped working showed more emotional symptoms and relevant changes in their perception of time.

Overall, given the evidence of the adverse behavioral and psychological impact of home confinement and social restrictions, effective measures needed to be in place to mitigate long-term effects on children and their mothers, especially those who have had to stop working during lockdown.

Overall, given the evidence of the adverse behavioral and psychological impact of home confinement and social restrictions, effective measures needed to be in place to mitigate long-term effects on children and their mothers, especially those who have had to stop working during lockdown.Visibility of low-contrast details in fluoroscopy and interventional radiology is important. Vismodegib nmr Assessing detail visibility with human observers typically suffers from large observer variances. Objective, quantitative measurement of low-contrast detail visibility using a model observer, such as the square of the signal-to-noise ratio rate (SNR2rate), was implemented in MATLAB™ and evaluated. The expected linear response of SNR2rate based on predictions by the so-called Rose model and frame statistics was verified. The uncertainty in the measurement of SNR2rate for a fixed imaging geometry was 6% based on 16 repeated measurements. The results show that, as expected, reduced object thickness and x-ray field size substantially improved SNR2rate/PKA,rate with PKA,rate being the air kerma area product rate. The measurement precision in SNR2rate/PKA,rate (8-9%) is sufficient to detect small but important improvements, may guide the selection of better imaging settings and provides a tool for teaching good radiological imaging techniques to clinical staff.