Differential activation of individual subunits in heteromeric kainate receptors

Neuronal kainate receptors are assembled from subunits with dissimilar specificities for agonists and antagonists. The composite biophysical behavior of heteromeric kainate receptors is determined by intersubunit interactions whose nature is unclear. Here we use dysiherbaine, a selective kainate receptor agonist, to show that GluR5 subunits assembled in heteromeric GluR5/KA-2 kainate receptor complexes can gate current without concomitant activation of their partner KA-2 subunits. A long-lasting interaction between dysiherbaine and GluR5 subunits elicits a tonic current from GluR5/KA-2 receptors; subsequent cooperative gating of KA-2 subunits can be elicited by both agonists, such as glutamate, and some classically defined antagonists, such as CNQX. This study demonstrates that each type of subunit within a heteromeric kainate receptor contributes a distinct conductance upon activation by agonist binding, and therefore provides insight into the biophysical function of ionotropic glutamate receptors.     

Insertional mutagenesis of the mouse acid ceramidase gene leads to early embryonic lethality in homozygotes and progressive lipid storage disease in heterozygotes

Ceramide is an important cellular lipid involved in signal transduction and the biosynthesis of complex sphingolipids. It can be hydrolyzed into sphingosine, another important signaling lipid, by the activity of ceramidases. Point mutations in the gene (Asah1) encoding one ceramidase, acid ceramidase (AC), lead to the lysosomal storage disorder Farber disease (FD). To investigate the role of AC in mammalian development, we disrupted the mouse gene Asah1 in embryonic stem cells by homologous recombination mediated insertion of an AC targeting vector into the wild-type sequence. Genotype analysis of over 150 offspring or embryos from heterozygous intercrosses revealed an absence of Asah1(-/-) individuals at embryonic day (E) 8.5 or later, although the ratio of wild-type to Asah1(+/-) individuals from these intercrosses was 1:2. Northern blot analysis showed that AC expression was turned on early in development, by E7.0, and continued through at least E17. In contrast, expression of the related lipid hydrolase, acid sphingomyelinase, was shut down by E11. Asah1(+/-) mice survived and lived a normal lifespan, but developed a progressive lipid storage disease in several of their organs, particularly the liver. These histopathological findings in Asah1(+/-) animals correlated with an up to twofold increase in the ceramide content of these tissues and a reduction n AC activity, confirming that the gene insertion event disrupted AC activity and ceramide metabolism. These results provide direct in vivo evidence that normal ceramide metabolism, and AC activity in particular, is essential for mammalian development. The animals and embryos described here should be a valuable resource for investigators studying the role of ceramide in cell growth and development, as well as those interested in the pathogenesis of FD and other sphingolipid storage disorders.     

Maternal dexamethasone treatment alters myosin isoform expression and contractile dynamics in fetal arteries

We tested the hypothesis that maternal glucocorticoid treatment modulates 17-kDa myosin light chain (myosin LC17) isoform expression and contractile dynamics in fetal ovine carotid arteries. In the single course group, ewes received 6 mg dexamethasone or placebo over 48 h. In the repeated course group, ewes received 6 mg dexamethasone or placebo weekly for 5 wk. In response to 1 microM phenylephrine, arteries from fetuses of dexamethasone-treated ewes exhibited biphasic contractions, characterized by an intermediate relaxation phase. The relaxation rate constant was significantly higher in arteries from the fetuses of dexamethasone than placebo-treated ewes. The observed biphasic contractions suggest the appearance of functional sarcoplasmic reticulum in the arteries from the fetuses of dexamethasone-treated ewes. The myosin LC17(a) isoform expression was lower in the arteries from the fetuses of the placebo-treated ewes than in those from the ewes. Repeated maternal administration of dexamethasone induced an almost twofold increase in myosin LC17(a) isoform expression in the fetal arteries. In contrast, maternal myosin LC17a isoform expression was not affected by dexamethasone treatment. We speculate that dexamethasone-induced increases in fetal myosin LC17(a) isoform expression represent accelerated differentiation of a subpopulation of vascular smooth muscle cells from the fetal to adult phenotype.     

Enhanced responsiveness to nitric oxide, nitroxyl anions, and nitrergic transmitter by 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole in the rat anococcygeus muscle.

The effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) on responses to sodium nitroprusside (SNP), S-nitroso-N-acetyl-penicillamine (SNAP), the nitroxyl anion donor Angeli's salt, and nitrergic nerve stimulation, as well as the release of NO from nitrergic nerves, were studied in the rat isolated anococcygeus muscle. YC-1 (1-100 microM) produced concentration-dependent relaxations in contracted muscles, which were partially but significantly reduced by the inhibitor of soluble guanylate cyclase (sGC), 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 1 and 10 microM). At a concentration that did not affect tissue tension, YC-1 (1 microM) significantly enhanced relaxations to SNP, SNAP, and Angeli's salt but did not affect relaxations to papaverine (10 microM). Nitrergic relaxations elicited by short periods (1 Hz for 10 s, 15 V) and long periods of EFS (5 Hz for 5 min, 15 V) were also enhanced by YC-1. YC-1 (100 microM), in an l-NAME and tetrodotoxin-insensitive manner, also increased the amount of NO detected in the organ bath media after the tissue was field stimulated (5 Hz for 5 min), which may have resulted from the electrolytic degradation of YC-1, as this effect was also seen in the absence of tissue. In summary, YC-1 enhanced relaxations to donors of NO, Angeli's salt, and nitrergic nerve stimulation in the rat anococcygeus muscle; however, the enhanced release of NO by YC-1 following nitrergic nerve stimulation was not a tissue-dependent effect.     

Plasmonic metasurface for light absorption enhancement in GaAs thin film

Plasmonics - Using the plasmonic metasurface, we have designed a highly efficient solar ray absorber by tailoring the thickness of the metallic arrays. The geometric-dependent local surface plasmon...     

Polymerase chain reaction analysis of laboratory generated bioaerosols

The common methods for analyzing bioaerosols are based on maintaining organism viability and quantifying culturability which may result in the underestimation of microbial concentrations. The present study employed a well-developed technique that only requires cellular DNA to identify organisms. Polymerase chain reaction (PCR) was chosen to amplify specific DNA sequence from an organism, to detect and semi-quantify organisms. Suspensions ofFrancisella tularensis were aerosolized in a chamber, and air samples were collected using impingers. Samples were analyzed using limiting dilution PCR, and the results compared with those from a traditional plate counting. Results indicated that the limiting dilution PCR provides a new way to identify and quantify bioaerosols that does not rely on viability and culturability. Therefore, the method would provide a more reliable estimate of airborne bacterial concentrations compared to traditional plate counts.     

Formation of Avenacein Y by<Emphasis Type="Italic">Fusarium avenaceum</Emphasis> Fries Sacc. isolates from poland and biological properties of the compound

Eighteen isolates ofFusarium avenaceum Fries Sacc. originating from cereals, potato and carrot from Poland synthesized Avenacein Y in amounts ranging from 0.01 to 2.0 g/kg of wheat grain. The compound was produced in 1 kg of corn kernels by isolate KF-58, isolated, identified and used to test for antibiotic activity against plant pathogenic fungi of 11 genera. Application of Avenacein Y caused slight decrease of mycelium growth in four species only.     

Free proline contents in two different groups of rice mutants resistant to hydroxy-L-proline

Summary In four rice (Oryza sativa L.) mutants resistant to hydroxy-L-proline (Hyp), HYP101, HYP203, HYP205 and HYP210, and in their original variety, Nipponbare, free proline and Hyp contents in the seeds and in the 14-day-old seedlings have been determined. The four mutants can be divided into two groups: HYP101 and HYP203 are classified as to recessive gene and the levels of free proline are similar to that of the original variety; the second group includes mutants HYP205 and HYP210 where the Hyp resistance is transmitted heterozygously and, both in the seeds and in the seedlings, a remarkable increase in free proline content is observed. In particular, free proline contents in the seeds of HYP205 and HYP210 are, respectively, 24 and 12 times that of the original variety. Hyp is detected only in the seedlings cultured with Hyp solution. In the Hyp resistant seedlings of HYP205 and HYP210, Hyp contents are twice that of the original variety and less than half in the seedlings of HYP101 and HYP203. Hyp resistance and differential proline levels are also evident in the callus initiated from the mutants. This suggests that the Hyp resistant mutants are good genetic markers both in planta and in vitro. The Hyp mutants are also discussed with regard to stress resistance.     

Urgent-Start Peritoneal Dialysis and Hemodialysis in ESRD Patients: Complications and Outcomes

BackgroundSeveral studies have suggested that urgent-start peritoneal dialysis (PD) is a feasible alternative to hemodialysis (HD) in patients with end-stage renal disease (ESRD), but the impact of the dialysis modality on outcome, especially on short-term complications, in urgent-start dialysis has not been directly evaluated. The aim of the current study was to compare the complications and outcomes of PD and HD in urgent-start dialysis ESRD patients.MethodsIn this retrospective study, ESRD patients who initiated dialysis urgently without a pre-established functional vascular access or PD catheter at a single center from January 2013 to December 2014 were included. Patients were grouped according to their dialysis modality (PD and HD). Each patient was followed for at least 30 days after catheter insertion (until January 2016). Dialysis-related complications and patient survival were compared between the two groups.ResultsOur study enrolled 178 patients (56.2% male), of whom 96 and 82 patients were in the PD and HD groups, respectively. Compared with HD patients, PD patients had more cardiovascular disease, less heart failure, higher levels of serum potassium, hemoglobin, serum albumin, serum pre-albumin, and lower levels of brain natriuretic peptide. There were no significant differences in gender, age, use of steroids, early referral to a nephrologist, prevalence of primary renal diseases, prevalence of co-morbidities, and other laboratory characteristics between the groups. The incidence of dialysis-related complications during the first 30 days was significantly higher in HD than PD patients. HD patients had a significantly higher probability of bacteremia compared to PD patients. HD was an independent predictor of short-term (30-day) dialysis-related complications. There was no significant difference between PD and HD patients with respect to patient survival rate.ConclusionIn an experienced center, PD is a safe and feasible dialysis alternative to HD for ESRD patients with an urgent need for dialysis.     

Telocytes in exercise‐induced cardiac growth

Exercise can induce physiological cardiac growth, which is featured by enlarged cardiomyocyte cell size and formation of new cardiomyocytes. Telocytes (TCs) are a recently identified distinct interstitial cell type, existing in many tissues and organs including heart. TCs have been shown to form a tandem with cardiac stem/progenitor cells in cardiac stem cell niches, participating in cardiac regeneration and repair. Although exercise‐induced cardiac growth has been confirmed as an important way to promote cardiac regeneration and repair, the response of cardiac TCs to exercise is still unclear. In this study, 4 weeks of swimming training was used to induce robust healthy cardiac growth. Exercise can induce an increase in cardiomyocyte cell size and formation of new cardiomyocytes as determined by Wheat Germ Lectin and EdU staining respectively. TCs were identified by three immunofluorescence stainings including double labelling for CD34/vimentin, CD34/platelet‐derived growth factor (PDGF) receptor‐α and CD34/PDGF receptor‐β. We found that cardiac TCs were significantly increased in exercised heart, suggesting that TCs might help control the activity of cardiac stem/progenitor cells, cardiomyocytes or endothelial cells. Adding cardiac TCs might help promote cardiac regeneration and renewal.