40 research outputs found

    Simvastatin Alters the RhoA Adaptation to Skeletal Muscle Stress Conditions

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    Soil Moisture ActivePassive (SMAP) L-Band Microwave Radiometer Post-Launch Calibration

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    The SMAP microwave radiometer is a fully-polarimetric L-band radiometer flown on the SMAP satellite in a 6 AM/ 6 PM sun-synchronous orbit at 685 km altitude. Since April, 2015, the radiometer is under calibration and validation to assess the quality of the radiometer L1B data product. Calibration methods including the SMAP L1B TA2TB (from Antenna Temperature (TA) to the Earths surface Brightness Temperature (TB)) algorithm and TA forward models are outlined, and validation approaches to calibration stability/quality are described in this paper including future work. Results show that the current radiometer L1B data satisfies its requirements

    Calcium dysregulation, functional calpainopathy, and endoplasmic reticulum stress in sporadic inclusion body myositis

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    Sporadic inclusion body myositis (IBM) is the most common primary myopathy in the elderly, but its pathoetiology is still unclear. Perturbed myocellular calcium (Ca2+) homeostasis can exacerbate many of the factors proposed to mediate muscle degeneration in IBM, such as mitochondrial dysfunction, protein aggregation, and endoplasmic reticulum stress. Ca2+ dysregulation may plausibly be initiated in IBM by immune-mediated membrane damage and/or abnormally accumulating proteins, but no studies to date have investigated Ca2+ regulation in IBM patients. We first investigated protein expression via immunoblot in muscle biopsies from IBM, dermatomyositis, and non-myositis control patients, identifying several differentially expressed Ca2+-regulatory proteins in IBM. Next, we investigated the Ca2+-signaling transcriptome by RNA-seq, finding 54 of 183 (29.5%) genes from an unbiased list differentially expressed in IBM vs. controls. Using an established statistical approach to relate genes with causal transcription networks, Ca2+ abundance was considered a significant upstream regulator of observed whole-transcriptome changes. Post-hoc analyses of Ca2+-regulatory mRNA and protein data indicated a lower protein to transcript ratio in IBM vs. controls, which we hypothesized may relate to increased Ca2+-dependent proteolysis and decreased protein translation. Supporting this hypothesis, we observed robust (4-fold) elevation in the autolytic activation of a Ca2+-activated protease, calpain-1, as well as increased signaling for translational attenuation (eIF2α phosphorylation) downstream of the unfolded protein response. Finally, in IBM samples we observed mRNA and protein under-expression of calpain-3, the skeletal muscle-specific calpain, which broadly supports proper Ca2+ homeostasis. Together, these data provide novel insight into mechanisms by which intracellular Ca2+ regulation is perturbed in IBM and offer evidence of pathological downstream effects.https://doi.org/10.1186/s40478-017-0427-

    Glycosylation of acetylcholinesterase and butyrylcholinesterase changes as a function of the duration of Alzheimer's disease

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    The identification of biochemical markers of Alzheimer's disease (AD) may help in the diagnosis of the disease. Previous studies have shown that Aβ1–42 is decreased, and tau and phospho-tau are increased in AD cerebrospinal fluid (CSF). Our own studies have identified glycosylated isoforms of acetylcholinesterase (Glyc-AChE) and butyrylcholinesterase (Glyc-BuChE) that are increased in AD CSF. Glyc-AChE is increased in APP (SW) Tg2576 transgenic mice prior to amyloid plaque deposition, which suggests that Glyc-AChE may be an early marker of AD. The aim of this study was to determine whether Glyc-AChE or Glyc-BuChE is increased in CSF at early stages of AD and to compare the levels of these markers with those of Aβ1–42, tau and phospho-tau. Lumbar CSF was obtained ante mortem from 106 non-AD patients, including 15 patients with mild cognitive impairment (MCI), and 102 patients with probable AD. Glyc-AChE, tau and phospho-tau were significantly increased in the CSF of AD patients compared to non-neurological disease (NND) controls. Aβ1–42 was lower in the AD patients than in NND controls. A positive correlation was found between the levels of Glyc-AChE or Glyc-BuChE and disease duration. However, there was no clear correlation between the levels of tau, phospho-tau or Aβ1–42 and disease duration. The results suggest that Glyc-AChE and Glyc-BuChE are unlikely to be early markers of AD, although they may have value as markers of disease progression.This work was supported by research grants from the National Health and Medical Research Council of Australia, the RL Cooper Medical Research Foundation of Australia, by a sponsored research agreement with Axonyx Inc. (New York), Innogenetics (Belgium), and by the Swedish Medical Research Council. J. S.-V. was partially sponsored by a fellowship from Navarro Tripodi Foundation of Spain and Innogentics (Belgium) and by a grant from the MCyT of Spain (Ramón y Cajal Program).Peer reviewe

    Streptococcal peritonitis in Australian peritoneal dialysis patients: predictors, treatment and outcomes in 287 cases

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    Background There has not been a comprehensive, multi-centre study of streptococcal peritonitis in patients on peritoneal dialysis (PD) to date. Methods The predictors, treatment and clinical outcomes of streptococcal peritonitis were examined by binary logistic regression and multilevel, multivariate poisson regression in all Australian PD patients involving 66 centres between 2003 and 2006. Results Two hundred and eighty-seven episodes of streptococcal peritonitis (4.6% of all peritonitis episodes) occurred in 256 individuals. Its occurrence was independently predicted by Aboriginal or Torres Strait Islander racial origin. Compared with other organisms, streptococcal peritonitis was associated with significantly lower risks of relapse (3% vs 15%), catheter removal (10% vs 23%) and permanent haemodialysis transfer (9% vs 18%), as well as a shorter duration of hospitalisation (5 vs 6 days). Overall, 249 (87%) patients were successfully treated with antibiotics without experiencing relapse, catheter removal or death. The majority of streptococcal peritonitis episodes were treated with either intraperitoneal vancomycin (most common) or first-generation cephalosporins for a median period of 13 days (interquartile range 8–18 days). Initial empiric antibiotic choice did not influence outcomes. Conclusion Streptococcal peritonitis is a not infrequent complication of PD, which is more common in indigenous patients. When treated with either first-generation cephalosporins or vancomycin for a period of 2 weeks, streptococcal peritonitis is associated with lower risks of relapse, catheter removal and permanent haemodialysis transfer than other forms of PD-associated peritonitis.Stacey O'Shea, Carmel M Hawley, Stephen P McDonald, Fiona G Brown, Johan B Rosman, Kathryn J Wiggins, Kym M Bannister and David W Johnso

    Soil Moisture Active/Passive (SMAP) L-Band Microwave Radiometer Post-Launch Calibration Upgrade

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    Current performance and existing problems in SMAP radiometer L1B_TB version 3 data product are described. The post-launch calibration algorithm has been updated by calibrating the three calibration parameters (the equivalent noise temperature of the noise diode, the offset of the reference load, and the antenna gain) jointly by using the global ocean and CS with both 110o and 180o pitch maneuvers after the reflector emissivity is calibrated. The results show that both calibration drift during eclipse season and bias over CS are removed. The RMSDs of the calibration drift over both the global ocean and CS are less than 0.1 K, and the goals of the calibration algorithm upgrade are achieved for coming L1B_TB version 4 data release

    The Chlamydia psittaci Genome: A Comparative Analysis of Intracellular Pathogens

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    Chlamydiaceae are a family of obligate intracellular pathogens causing a wide range of diseases in animals and humans, and facing unique evolutionary constraints not encountered by free-living prokaryotes. To investigate genomic aspects of infection, virulence and host preference we have sequenced Chlamydia psittaci, the pathogenic agent of ornithosis.A comparison of the genome of the avian Chlamydia psittaci isolate 6BC with the genomes of other chlamydial species, C. trachomatis, C. muridarum, C. pneumoniae, C. abortus, C. felis and C. caviae, revealed a high level of sequence conservation and synteny across taxa, with the major exception of the human pathogen C. trachomatis. Important differences manifest in the polymorphic membrane protein family specific for the Chlamydiae and in the highly variable chlamydial plasticity zone. We identified a number of psittaci-specific polymorphic membrane proteins of the G family that may be related to differences in host-range and/or virulence as compared to closely related Chlamydiaceae. We calculated non-synonymous to synonymous substitution rate ratios for pairs of orthologous genes to identify putative targets of adaptive evolution and predicted type III secreted effector proteins.This study is the first detailed analysis of the Chlamydia psittaci genome sequence. It provides insights in the genome architecture of C. psittaci and proposes a number of novel candidate genes mostly of yet unknown function that may be important for pathogen-host interactions

    Understanding Factors Associated With Psychomotor Subtypes of Delirium in Older Inpatients With Dementia

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    Measures of frailty in population-based studies: An overview

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    Although research productivity in the field of frailty has risen exponentially in recent years, there remains a lack of consensus regarding the measurement of this syndrome. This overview offers three services: first, we provide a comprehensive catalogue of current frailty measures; second, we evaluate their reliability and validity; third, we report on their popularity of use

    Differences in kainate receptor involvement in hippocampal mossy fibre long-term potentiation depending on slice orientation

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    Long-term potentiation (LTP) is a well-established experimental model used to investigate the synaptic basis of learning and memory. LTP at mossy fibre – CA3 synapses in the hippocampus is unusual because it is normally N-methyl-d-aspartate (NMDA) receptor-independent. Instead it seems that the trigger for mossy fibre LTP involves kainate receptors (KARs). Although it is generally accepted that pre-synaptic KARs play an essential role in frequency facilitation and LTP, their subunit composition remains a matter of significant controversy. We have reported previously that both frequency facilitation and LTP can be blocked by selective antagonism of GluK1 (formerly GluR5/GluK5)-containing KARs, but other groups have failed to reproduce this effect. Moreover, data from receptor knockout and mRNA expression studies argue against a major role of GluK1, supporting a more central role for GluK2 (formerly GluR6/GluK6). A potential reason underlying the controversy in the pharmacological experiments may reside in differences in the preparations used. Here we show differences in pharmacological sensitivity of synaptic plasticity at mossy fibre – CA3 synapses depend critically on slice orientation. In transverse slices, LTP of fEPSPs was invariably resistant to GluK1-selective antagonists whereas in parasagittal slices LTP was consistently blocked by GluK1-selective antagonists. In addition, there were pronounced differences in the magnitude of frequency facilitation and the sensitivity to the mGlu2/3 receptor agonist DCG-IV. Using anterograde labelling of granule cells we show that slices of both orientations possess intact mossy fibres and both large and small presynaptic boutons. Transverse slices have denser fibre tracts but a smaller proportion of giant mossy fibre boutons. These results further demonstrate a considerable heterogeneity in the functional properties of the mossy fibre projection
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