DEVELOPMENT OF (Na + -K + )-ATPase IN RAT CEREBRUM: CORRELATION WITH Na + -DEPENDENT PHOSPHORYLATION AND K + - para NITROPHENYLPHOSPHATASE 1

The activities of (Na + K + )-ATPase and its proposed partial reactions, K + - p NPPase and Na + -dependent phosphorylation, all increase tenfold relative to microsomal protein between 5 days prior to birth and 60 days postnatally in NaI-treated rat cerebral microsomes, and all reach half of their adult values between the fifth and tenth postnatal day. These increases are concurrent with the most rapid changes in cerebral wet weight. Increases in the amount of the related phosphorylatable polypeptide during development. as estimated by densitometry of Coomassie-stained polyacrylamide gels after electrophoresis of constant amounts of microsomal protein dissolved in sodium dodecylsulfate, parallel the increments in levels of Na + -dependent phosphorylation. The fraction of total phosphorylation that is Na + -dependent increases steadily during development. suggesting a precursor role for some of the Na + -independent fraction. The results are consistent with a single biosynthetic control for the enzymatic sites critical to the partial reactions of (Na + -K + )-ATPase. No changes in turnover number or affinity for substrate or ligands were found during development. Little similarity was noted among the age-related changes of Mg 2+ -ATPase activity. Mg 2+ -paranitrophenylphosphatase activity, and Na + -independent phosphorylation levels. The most rapid changes in (Na + -K + )-ATPase take place during the period corresponding to glial proliferation and neuronal arborization.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66087/1/j.1471-4159.1978.tb06577.x.pd

DEVELOPMENT OF (Na + -K + )-ATPase IN RAT HINDBRAIN: INCREMENTS IN PARALLEL WITH Na + -DEPENDENT PHOSPHORYLATION AND K + - p NITROPHENYLPHOSPHATASE 1

Rat hindbrain NaI-enriched microsomal (Na + -K + )-ATPase activity, K + - p NPPase activity, and Na + -dependent steady-state phosphorylation levels all increase approx 10-fold relative to microsomal protein between 5 days prenatally and 60 days postnatally. These activities, as well as the mean wet weight of the hindbrain, are at half of their 60 day values shortly after the 10th postnatal day. For all ages, these hindbrain activities average over twice those found in the forebrain in a companion paper (Bertoni & Siegel, 1978). Increases during development in the amount of the related phosphorylatable polypeptide, estimated by densitometry of stained polyacrylamide gels containing fixed amounts of microsomal protein dissolved in SDS, are in agreement with increases in steady state levels of Na + -dependent phosphorylation. The fraction of total phosphorylation that is Na + -dependent rises steadily during development consistent with, but not obligatorily due to, a conversion of some of the previously Na + -independent portion. Mg2 + -ATPase and Mg 2+ - p NPPase activities and steady-state Na + ,-independent phosphorylation levels do not increase in parallel during development. These observations add further support to the proposed partial reaction scheme for (Na + - K + )-ATPase. The major increments in (Na + -K + )-ATPase occur simultaneously with the deposition of specialized plasma membranes, particularly in the molecular layer of the cerebellum, as described in previous studies of rat hind brain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65622/1/j.1471-4159.1979.tb00386.x.pd

Visualization of droplet condensation in membrane distillation desalination with surface modification: hydrophilicity, hydrophobicity, and wicking spacers

Condensation performance is a key target for improving the energy efficiency of thermal desalination technologies such as air gap membrane distillation (AGMD). This study includes the first visualization of condensation in AGMD, through the use of a high conductivity, transparent sapphire condenser surface. The study examines how flow patterns are affected by several novel modifications, including varied surface hydrophobicity, module tilt angle, and gap spacer design. The experimental results were analyzed with numerical modeling. While the orientation of the mesh spacer, which holds the air gap apart, was found to have no substantial effect on the permeate production rate, the surface's hydrophobicity or hydrophilicity did result in different rates. The hydrophobic surface exhibited fewer droplets bridging the gap, more spherical droplets, and better droplet shedding. For gap sizes less than ~3 mm, the hydrophilic surface frequently had regions of water pinned around the surface itself and the plastic spacer. While the flow patterns observed were more complex than the film condensation typically used to model the process, the simplified numerical modelling yielded good agreement with the data when an adjustment factor was used to account for the gap size

Glycemic Control, Complications, and Death in Older Diabetic Patients: The Diabetes and Aging Study

OBJECTIVE—To identify the range of glycemic levels associated with the lowest rates of complications and mortality in older diabetic patients. RESEARCH DESIGN AND METHODS—We conducted a retrospective cohort study (2004–2008) of 71,092 patients with type 2 diabetes, aged $60 years, enrolled in Kaiser Per-manente Northern California. We specified Cox proportional hazards models to evaluate the relationships between baseline glycated hemoglobin (A1C) and subsequent outcomes (nonfatal complications [acute metabolic, microvascular, and cardiovascular events] and mortality). RESULTS—The cohort (aged 71.06 7.4 years [means6 SD]) had a mean A1C of 7.06 1.2$11.0%). Mortality had a U-shaped relationship with A1C. Compared with the risk with A1C,6.0%, mortality risk was lower for A1C levels between 6.0 and 9.0 % (e.g., 0.83 [0.76–0.90] for A1C 7.0–7.9%) and higher at A1C$11.0$8.0%. Patterns generally were consistent across age-groups (60–69, 70–79, and $80 years). CONCLUSIONS—Observed relationships between A1C and combined end points suppor

Signatures of large composite Dark Matter states

We investigate the interactions of large composite dark matter (DM) states with the Standard Model (SM) sector. Elastic scattering with SM nuclei can be coherently enhanced by factors as large as A^2, where A is the number of constituents in the composite state (there exist models in which DM states of very large A > 10^8 may be realised). This enhancement, for a given direct detection event rate, weakens the expected signals at colliders by up to 1/A. Moreover, the spatially extended nature of the DM states leads to an additional, characteristic, form factor modifying the momentum dependence of scattering processes, altering the recoil energy spectra in direct detection experiments. In particular, energy recoil spectra with peaks and troughs are possible, and such features could be confirmed with only O(50) events, independently of the assumed halo velocity distribution. Large composite states also generically give rise to low-energy collective excitations potentially relevant to direct detection and indirect detection phenomenology. We compute the form factor for a generic class of such excitations - quantised surface modes - finding that they can lead to coherently-enhanced, but generally sub-dominant, inelastic scattering in direct detection experiments. Finally, we study the modifications to capture rates in astrophysical objects that follow from the elastic form factor, as well as the effects of inelastic interactions between DM states once captured. We argue that inelastic interactions may lead to the DM collapsing to a dense configuration at the centre of the object.Comment: 30 pages, 5 figures, v2; references and minor additional comments adde

CD4+ Regulatory and Effector/Memory T Cell Subsets Profile Motor Dysfunction in Parkinson’s Disease

Animal models and clinical studies have linked the innate and adaptive immune system to the pathology of Parkinson’s disease (PD). Despite such progress, the specific immune responses that influence disease progression have eluded investigators. Herein, we assessed relationships between T cell phenotype and function with PD progression. Peripheral blood lymphocytes from two separate cohorts, a discovery cohort and a validation cohort, totaling 113 PD patients and 96 age- and environment-matched caregivers were examined by flow cytometric analysis and T cell proliferation assays. Increased effector/memory T cells (Tem), defined as CD45RO+ and FAS+ CD4+ T cells and decreased CD31+ and α4β7+ CD4+ T cells were associated with progressive Unified Parkinson’s Disease Rating Scale III scores. However, no associations were seen between immune biomarkers and increased age or disease duration. Impaired abilities of regulatory T cells (Treg) from PD patients to suppress effector T cell function was observed. These data support the concept that chronic immune stimulation, notably Tem activation and Treg dysfunction is linked to PD pathobiology and disease severity, but not disease duration. The association of T cell phenotypes with motor symptoms provides fresh avenues for novel biomarkers and therapeutic designs

Diabetic cardiomyopathy

Diabetic cardiomyopathy is a distinct primary disease process, independent of coronary artery disease, which leads to heart failure in diabetic patients. Epidemiological and clinical trial data have confirmed the greater incidence and prevalence of heart failure in diabetes. Novel echocardiographic and MR (magnetic resonance) techniques have enabled a more accurate means of phenotyping diabetic cardiomyopathy. Experimental models of diabetes have provided a range of novel molecular targets for this condition, but none have been substantiated in humans. Similarly, although ultrastructural pathology of the microvessels and cardiomyocytes is well described in animal models, studies in humans are small and limited to light microscopy. With regard to treatment, recent data with thiazoledinediones has generated much controversy in terms of the cardiac safety of both these and other drugs currently in use and under development. Clinical trials are urgently required to establish the efficacy of currently available agents for heart failure, as well as novel therapies in patients specifically with diabetic cardiomyopathy