Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses ...over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.
ABSTRACT We report on the extensive multi-wavelength observations of the blazar Markarian 421 (Mrk 421) covering radio to γ-rays, during the 4.5 year period of ARGO-YBJ and Fermi common operation ...time, from 2008 August to 2013 February. These long-term observations, extending over an energy range of 18 orders of magnitude, provide a unique chance to study the variable emission of Mrk 421. In particular, due to the ARGO-YBJ and Fermi data, the entire energy range from 100 MeV to 10 TeV is covered without any gap. In the observation period, Mrk 421 showed both low- and high-activity states at all wavebands. The correlations among flux variations in different wavebands were analyzed. The X-ray flux is clearly correlated with the TeV γ-ray flux, while the GeV γ-rays only show a partial correlation with the TeV γ-rays. Radio and UV fluxes seem to be weakly or not correlated with the X-ray and γ-ray fluxes. Seven large flares, including five X-ray flares and two GeV γ-ray flares with variable durations (3-58 days), and one X-ray outburst phase were identified and used to investigate the variation of the spectral energy distribution with respect to a relative quiescent phase. During the outburst phase and the seven flaring episodes, the peak energy in X-rays is observed to increase from sub-keV to a few keV. The TeV γ-ray flux increases up to 0.9-7.2 times the flux of the Crab Nebula. The behavior of GeV γ-rays is found to vary depending on the flare, a feature that leads us to classify flares into three groups according to the GeV flux variation. Finally, the one-zone synchrotron self-Compton model was adopted to describe the emission spectra. Two out of three groups can be satisfactorily described using injected electrons with a power-law spectral index around 2.2, as expected from relativistic diffuse shock acceleration, whereas the remaining group requires a harder injected spectrum. The underlying physical mechanisms responsible for different groups may be related to the acceleration process or to the environment properties.
“U” curve association of blood pressure and mortality in hemodialysis patients.
Hypertension may play an important role in the pathogenesis of the excess cardiovascular and cerebrovascular (CV) ...morbidity observed in hemodialysis patients (HD). However, the optimal blood pressure (BP) range for HD patients has not been defined. We postulated that there is a “U” curve relationship between BP and CV mortality. To explore this hypothesis we studied 5,433 HD patients in Dialysis Clinic Inc., a large not-for-profit chain, over a five year period.
Cox regression, with fixed and time-varying covariates, was used to assess the effect of systolic blood pressure (SBP) and diastolic blood pressure (DBP), pre- and post-dialysis, on CV mortality, while adjusting for age, gender, ethnicity, primary cause of end-stage renal disease, Kt/V, serum albumin, and antihypertensive medications.
The overall impact of BP on CV mortality was modest. Pre-dialysis, neither systolic nor diastolic hypertension were associated with an increase in CV mortality. Post-dialysis, SBP ≥ 180mm Hg (RR = 1.96, P < 0.015) and DBP ≥ 90mm Hg (RR = 1.73, P < 0.05) were associated with increased CV mortality. Low SBP (SBP < 110mm Hg) was associated with increased CV mortality, pre- and post-dialysis.
The results suggest the presence of a “U” curve relationship between SBP post-dialysis and CV mortality in HD patients.
Spontaneous bioelectric activity (SBA) taking the form of extracellularly recorded spike trains (SBA) has been quantitatively analyzed in organotypic neonatal rat visual cortex explants at different ...ages in vitro, and the effects investigated of both short- and long-term pharmacological suppression of glutamatergic synaptic transmission. In the presence of APV, a selective NMDA receptor blocker, 1–2- (but not 3-)week-old cultures recovered their previous SBA levels in a matter of hours, although in imitation of the acute effect of the GABAergic inhibitor picrotoxin (PTX), bursts of action potentials were abnormally short and intense. Cultures treated either overnight or chronically for 1–3 weeks with APV, the AMPA/kainate receptor blocker DNQX, or a combination of the two were found to display very different abnormalities in their firing patterns. NMDA receptor blockade for 3 weeks produced the most severe deviations from control SBA, consisting of greatly prolonged and intensified burst firing with a strong tendency to be broken up into trains of shorter spike clusters. This pattern was most closely approximated by acute GABAergic disinhibition in cultures of the same age, but this latter treatment also differed in several respects from the chronic-APV effect. In 2-week-old explants, in contrast, it was the APV+DNQX treated group which showed the most exaggerated spike bursts. Functional maturation of neocortical networks, therefore, may specifically require NMDA receptor activation (not merely a high level of neuronal firing) which initially is driven by endogenous rather than afferent evoked bioelectric activity. Putative cellular mechanisms are discussed in the context of a thorough review of the extensive but scattered literature relating activity-dependent brain development to spontaneous neuronal firing patterns.
Glutamate synthase is a multicomponent iron-sulfur flavoprotein belonging to the class of N-terminal nucleophile amidotransferases. It catalyzes the conversion of L-glutamine and 2-oxoglutarate into ...two molecules of L-glutamate. In recent years the X-ray structures of the ferredoxin-dependent glutamate synthase and of the a subunit of the NADPH-dependent glutamate synthase have become available. Thanks to X-ray crystallography, it is now known that the ammonia reaction intermediate is transferred via an intramolecular tunnel from the amidotransferase domain to the synthase domain over a distance of about 32A. Although ammonia channeling is a recurrent theme for N-terminal nucleophile and triad-type amidotransferases, the molecular mechanisms of ammonia transfer and its control are different for each known amidotransferase. This review focuses on the intriguing mechanism of action and self-regulation of glutamate synthase with a special focus on the structural data.
•A novel application of electric spring (ES) presented – maintaining constant power through an impedance-varying load.•Two methods proposed – a linear approximation-based open-loop control and a ...PI-based closed loop control to test the constant power performance of ES.•The proposed approaches validated through simulation studies and experimental setup, close correlation observed.•Proposed techniques compared, advantages and disadvantages of both methods highlighted.
Electric spring has recently been proposed as a special type of reactive power compensator to improve various attributes of the smart grid. Its extended functionality and applications are yet to be explored. This paper presents a new application of electric spring to ensure constant power across the loading elements under impedance variations. Two control methodologies are proposed to carry out this task: a linear approximation configuration and a closed-loop configuration. Design and mathematical analysis are provided, and the results of both control configurations are analyzed for a simulation model as well as a hardware setup. It has been found that experimental results are congruent with those obtained from the simulation model, hence ensuring the efficacy of theoretical framework.
The microstructure, magnetic and magnetocaloric properties are investigated in the melt-spun and annealed Ni42.9Co6.9Mn38.3Sn11.9 ribbons. The columnar grains grow perpendicular to ribbon surfaces. ...After annealing, the grain size increases greatly. Meanwhile, the parent phase is suppressed and therefore L10 martensite predominates, indicating obvious shift of martensitic transformation to high temperature. More interestingly, the martensite variants are distinctly observed on the fractured cross-section of annealed ribbons, not just on the free surface in general. The significant enhancement of magnetic entropy change and effective refrigerant capacities with relatively smaller thermal hysteresis make annealed ribbons potential candidate in magnetic refrigeration around room temperature.
The present study describes two newly developed N-terminal pro-peptides of collagen type I (PINP) competitive enzyme-linked immunosorbent assays (ELISAs) for the assessment of corresponding PINP ...epitopes in the rat- and human species.
Monoclonal antibodies were raised against corresponding rat and human PINP sequences and competitive assays were developed for each species. They were evaluated in relevant pre-clinical or clinical studies.
The antibody characterizations indicated that PINP indeed was recognized. Technical robust assays were obtained. Rat PINP and tALP showed similar patterns in the gold standard osteoporosis rat ovariectomized (OVX) model. No liver contribution was observed in the liver fibrosis rat bile duct ligation model (BDL). In an osteoporosis study, the human serum PINP levels were significantly decreased after ibandronate treatment compared to placebo.
The two corresponding PINP assays were specific and these bone turnover markers may improve translational science for the evaluation for bone-related diseases.
To characterize the metabolic " fingerprint" of fecal extracts for diagnosis of early-stage colorectal cancer(CRC)using proton nuclear magnetic resonance spectroscopy(
H-NMR)-based metabolomics ...coupled with pattern recognition.
From January 2014 to December 2014, we collected fecal samples at the Second Affiliated Hospital of Shantou University Medical College, from 25 patients with colorectal adenomas(CR-Ad), 20 with stage Ⅰ/Ⅱ CRC, and 32 healthy controls(HCs). The patients were diagnosed by histopathology. No subjects had any complicating diseases. HCs showed no abnormalities from blood tests, endoscopic examination, diagnostic imaging, and/or medical interviews. We excluded participants who used antibiotics, NSAIDS, statins, or probiotics within two months of study participation, and any patients who underwent chemotherapy or radiation treatments prior to surgery. We used orthogonal partial least-squares-discriminant analysis(OPLS-DA)for pattern recognition(dimension reduction)on
H-NMR processed data(
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Transcriptomic and proteomic analysis were performed on 72 h biofilms of the acneic strain Cutibacterium acnes and planktonic cultures in the presence of epinephrine. Epinephrine predominantly ...downregulated genes associated with various transporter proteins. No correlation was found between proteomic and transcriptomic profiles. In control samples, the expression of 51 proteins differed between planktonic cultures and biofilms. Addition of 5 nM epinephrine reduced this number, and in the presence of 5 µM epinephrine, the difference in proteomic profiles between planktonic cultures and biofilms disappeared. According to the proteomic profiling, epinephrine itself was more effective in the case of C. acnes biofilms and potentially affected the tricarboxylic acid cycle (as well as alpha-ketoglutarate decarboxylase Kgd), biotin synthesis, cell division, and transport of different compounds in C. acnes cells. These findings are consistent with recent research on Micrococcus luteus , suggesting that the effects of epinephrine on actinobacteria may be universal.
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