Tracking neurons across days with high-density probes.

Neural activity spans multiple time scales, from milliseconds to months. Its evolution can be recorded with chronic high-density arrays such as Neuropixels probes, which can measure each spike at tens of sites and record hundreds of neurons. These probes produce vast amounts of data that require different approaches for tracking neurons across recordings.

Fitness enhances psychosocial well-being and self-confidence in young men with hemophilia: Results from Project GYM.

Introduction: Contemporary hemophilia care supports physical activity, its benefits being well recognized. Despite recognition of the psychological challenges encountered by people with hemophilia, little is known about the psychological impact of physical fitness in this population.

Aim: To identify changes in psychological well-being in young men with hemophilia through participation in a gym program.

Project GYM: A randomized feasibility study investigating effect on motivation of personal trainer-led exercise in young men with hemophilia.

Introduction: Many young men with hemophilia engage in physical activity and sport but face challenges to participation because of their hemophilia. Project GYM aimed to investigate the feasibility of a hemophilia-specific fitness program led by a personal trainer (PT) and its impact on gym activity, motivation, and adherence to exercise.

Methods: This was a nonblinded, randomized feasibility study, recruiting participants aged 18 to 25 years with hemophilia A or B (all severities, ± inhibitor) from three London hemophilia centers.

The UK haemophilia specialist nurse: Competencies fit for practice in the 21st century.

Introduction: Nurses play a central co-ordinating role in delivering comprehensive care for people with haemophilia and allied bleeding disorders, for which they need a broad range of competencies. The UK Haemophilia Nurses Association (HNA) published a role description in 1994 which was developed into a competency framework in 2014. This has now been updated to reflect current educational and clinical practice.

TMEM41B is a novel regulator of autophagy and lipid mobilization.

Autophagy maintains cellular homeostasis by targeting damaged organelles, pathogens, or misfolded protein aggregates for lysosomal degradation. The autophagic process is initiated by the formation of autophagosomes, which can selectively enclose cargo via autophagy cargo receptors. A machinery of well-characterized autophagy-related proteins orchestrates the biogenesis of autophagosomes; however, the origin of the required membranes is incompletely understood.

The pleiotropic deubiquitinase Ubp3 confers aneuploidy tolerance.

Aneuploidy-or an unbalanced karyotype in which whole chromosomes are gained or lost-causes reduced fitness at both the cellular and organismal levels but is also a hallmark of human cancers. Aneuploidy causes a variety of cellular stresses, including genomic instability, proteotoxic and oxidative stresses, and impaired protein trafficking. The deubiquitinase Ubp3, which was identified by a genome-wide screen for gene deletions that impair the fitness of aneuploid yeast, is a key regulator of aneuploid cell homeostasis.

Chromosome-Specific and Global Effects of Aneuploidy in Saccharomyces cerevisiae.

Aneuploidy, an unbalanced karyotype in which one or more chromosomes are present in excess or reduced copy number, causes an array of known phenotypes including proteotoxicity, genomic instability, and slowed proliferation. However, the molecular consequences of aneuploidy are poorly understood and an unbiased investigation into aneuploid cell biology is lacking. We performed high-throughput screens for genes the deletion of which has a synthetic fitness cost in aneuploidy Saccharomyces cerevisiae cells containing single extra chromosomes.

Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast.

Aneuploidy causes severe developmental defects and is a near universal feature of tumor cells. Despite its profound effects, the cellular processes affected by aneuploidy are not well characterized. Here, we examined the consequences of aneuploidy on the proteome of aneuploid budding yeast strains.

Aneuploidy causes proteotoxic stress in yeast.

Gains or losses of entire chromosomes lead to aneuploidy, a condition tolerated poorly in all eukaryotes analyzed to date. How aneuploidy affects organismal and cellular physiology is poorly understood. We found that aneuploid budding yeast cells are under proteotoxic stress.

Congenital hypothyroidism with goiter in Tenterfield terriers.

Background: A cluster of cases of congenital hypothyroidism with goiter (CHG) in Tenterfield Terriers was identified and hypothesized to be dyshormonogenesis of genetic etiology with autosomal recessive inheritance.

Objectives: To describe the phenotype, thyroid histopathology, biochemistry, mode of inheritance, and causal mutation of CHG in Tenterfield Terriers.

Animals: Thyroid tissue from 1 CHG-affected Tenterfield Terriers, 2 affected Toy Fox Terriers, and 7 normal control dogs.

Topiramate as an inhibitor of carbonic anhydrase isoenzymes.

Purpose: This study investigated the effectiveness of topiramate (TPM) as an inhibitor of six isozymes of carbonic anhydrase (CA).

Methods: The inhibition constants (Ki) of TPM and acetazolamide (AZM) for CA I, CA II, CA III, CA IV, CA V, and CA VI were determined for human (HCA), rat (RCA), or mouse (MCA). The activity of CA was studied by using purified isozymes, erythrocytes, subcellular fractions of kidney or brain, and saliva, and was assayed at 37 degrees C or 25 degrees C by 18O mass spectrometry and/or by measuring the pH shift at 0 degrees C.

Mechanism of the acceleration of CO2 production from pyruvate in liver mitochondria by HCO3-.

To investigate the mechanism by which HCO3- accelerates pyruvate metabolism in guinea pig liver mitochondria, we measured continuously, at pH 7.4 and 37 degrees C, 13C16O2 production from [1-13C]pyruvate by mass spectrometry and NADH concentration by fluorescence and analyzed total malate, citrate, and beta-hydroxybutyrate produced by standard biochemical methods. When [1-13C]pyruvate is added to the mitochondrial suspension, 13C16O2 concentration rises steeply in the first seconds and then slows to a steady lower rate.

Continuous measurement of 13C16O2 production from [13C]pyruvate by intact liver mitochondria: effect of HCO3-.

We have measured continuously the production of mass 45 CO2(13C16O2) from 13C-labeled pyruvate in a guinea pig liver mitochondrial suspension and simultaneously the O2 consumption at 37 degrees C and pH 7.4. The reactions took place in a closed 3-ml volume, stirred, thermoregulated chamber separated from the ion source of a mass spectrometer by a gas-permeable membrane that permitted recording the mass peaks of any gas dissolved in the reaction mixture with a response time as fast as 3 s.

Role of hepatic carbonic anhydrase in de novo lipogenesis.

The role of carbonic anhydrase in de novo lipid synthesis was examined by measuring [1-14C]acetate incorporation into total lipids, fatty acids and non-saponifiable lipids in freshly isolated rat hepatocytes. Two carbonic anhydrase inhibitors, trifluoromethylsulphonamide (TFMS) and ethoxozolamide (ETZ) decreased incorporation of 14C into total lipids. Both fatty acid and non-saponifiable lipid components of the total lipid were inhibited to approximately the same extent by 100 microM TFMS (29 +/- 0.

Topiramate: preclinical evaluation of structurally novel anticonvulsant.

Topiramate [TPM, 2,3:4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate] (RWJ-17021-000, formerly McN-4853) is a structurally novel antiepileptic drug (AED). The preclinical anticonvulsant profile suggests that TPM acts primarily by blocking the spread of seizures. TPM was highly effective in the maximal electroshock (MES) seizure test in rats and mice.

Carbonic anhydrases in cytosol, nucleus, and membranes of rat liver.

The relative contribution of each functional carbonic anhydrase (CA) isozyme to liver CA activity of fed or starved adult male rats has been determined. The functional isozymes are CA II, CA III, CA IV, and CA V. Total CA, CA III, CA II, CA IV, and CA V activities (in mumol CO2 converted.

Differentiation-dependent expression of carbonic anhydrase II and III in 3T3 adipocytes.

Carbonic anhydrase (CA) was examined in two adipocyte cell lines, 3T3-L1 and 3T3-F442A. Both CA III and non-CA III activities, measured by 18O mass spectrometry, were present in 3T3-L1 and 3T3-F442A adipocytes; however, no CA activity was detected in 3T3 preadipocytes of either line. These observations were supported by immunoblot experiments employing CA III and CA II isoform-specific antisera.

Carbonic anhydrase III in obese Zucker rats.

Proteins from 5- to 7-wk-old lean and obese Zucker rats were separated by one-dimensional sodium dodecyl sulfate (SDS) and two-dimensional SDS-isoelectric focusing-polyacrylamide gel electrophoresis. Laser densitometry revealed an obesity-related decrease in the concentration of a 28-kDa cytosolic adipocyte protein, the most abundant protein in adipocytes from lean Zucker rats. Microsequencing revealed the identity of this protein to be carbonic anhydrase III (CA III).

Carbonic anhydrase in the membrane of the endoplasmic reticulum of male rat liver.

We have prepared subcellular fractions of male rat liver homogenate by the method of Lewis and Tata [Lewis, J. A. & Tata, J.