Type-I interferons induce lung protease responses following respiratory syncytial virus infection via RIG-I-like receptors

The role of proteases in viral infection of the lung is poorly understood. Thus, we examined matrix metalloproteinases (MMPs) and cathepsin proteases in respiratory syncytial virus (RSV)-infected mouse lungs. RSV-induced gene expression for MMPs -2, -3, -7, -8, -9, -10, -12, -13, -14, -16, -17, -19, -20, -25, -27, and -28 and cathepsins B, C, E, G, H, K, L1, S, W, and Z in the airways of Friend leukemia virus B sensitive strain mice. Increased proteases were present in the bronchoalveolar lavage fluid (BALF) and lung tissue during infection. Mitochondrial antiviral-signaling protein (MAVS) and TIR-domain-containing adapter-inducing interferon-β-deficient mice were exposed to RSV. <i>Mavsi>-deficient mice had significantly lower expression of airway MMP-2, -3, -7, -8, -9, -10, -12, -13, and -28 and cathepsins C, G, K, S, W, and Z. In lung epithelial cells, retinoic acid-inducible gene-1 (RIG-I) was identified as the major RIG-I-like receptor required for RSV-induced protease expression via MAVS. Overexpression of RIG-I or treatment with interferon-β in these cells induced MMP and cathepsin gene and protein expression. The significance of RIG-1 protease induction was demonstrated by the fact that inhibiting proteases with batimastat, E64 or ribavirin prevented airway hyperresponsiveness and enhanced viral clearance in RSV-infected mice.

Effect of polyethylenimine, a cell permeabilizer, on the photosensitized destruction of algae by methylene blue and nuclear fast red

The present study reports the effect a cell permeabilizer, polyethylenimine (PEI) has on the photodynamic effect of methylene blue (MB) and nuclear fast red (NFR) in the presence of hydrogen peroxide (H₂O₂). The photosensitized destruction of the algae Chlorella vulgaris under irradiation with visible light is examined. The photodynamic effect was investigated under aerobic and anaerobic conditions. The presence of a permeabilizer during the photosensitized destruction of C. vulgaris does not enhance the activity of the MB, MB/H₂O₂ system or the NFR, NFR/H₂O ₂ system under aerobic conditions. However under anaerobic conditions we have determined that when a cell permeabilizer was added to the MB/H ₂O₂ system, the photosensitized destruction of C. vulgaris proceeded via a combination of Type I and Type II mechanisms. The presence of PEI enforces MB/H₂O₂ to be active toward the destruction of C. vulgaris whether oxygen is present or absent. Under aerobic and anaerobic conditions the activity of NFR was suppressed in the presence of PEI as a result of electrostatic interactions between the photosensitizer and the cell permeabilizer. The decrease in fluorescence recorded is indicative of destruction of the chlorophyll a pigment. 

Magnitude differences in bioactive compounds, chemical functional groups, fatty acid profiles, nutrient degradation and digestion, molecular structure and metabolic characteristics of protein in newly developed yellow-seeded and black-seeded canola lines.

Recently, new lines of yellow-seeded (CS-Y) and black-seeded canola (CS-B) have been developed with chemical and structural alteration through modern breeding technology. However, no systematic study was found on the bioactive compounds, chemical functional groups, fatty acid profiles, inherent structure, nutrient degradation and absorption, or metabolic characteristics between the newly developed yellow- and black-seeded canola lines. This study aimed to systematically characterize chemical, structural, and nutritional features in these canola lines. The parameters accessed include bioactive compounds and antinutrition factors, chemical functional groups, detailed chemical and nutrient profiles, energy value, nutrient fractions, protein structure, degradation kinetics, intestinal digestion, true intestinal protein supply, and feed milk value. The results showed that the CS-Y line was lower (P ≤ 0.05) in neutral detergent fiber (122 vs 154 g/kg DM), acid detergent fiber (61 vs 99 g/kg DM), lignin (58 vs 77 g/kg DM), nonprotein nitrogen (56 vs 68 g/kg DM), and acid detergent insoluble protein (11 vs 35 g/kg DM) than the CS-B line. There was no difference in fatty acid profiles except C20:1 eicosenoic acid content (omega-9) which was in lower in the CS-Y line (P < 0.05) compared to the CS-B line. The glucosinolate compounds differed (P < 0.05) in terms of 4-pentenyl, phenylethyl, 3-CH3-indolyl, and 3-butenyl glucosinolates (2.9 vs 1.0 μmol/g) between the CS-Y and CS-B lines. For bioactive compounds, total polyphenols tended to be different (6.3 vs 7.2 g/kg DM), but there were no differences in erucic acid and condensed tannins with averages of 0.3 and 3.1 g/kg DM, respectively. When protein was portioned into five subfractions, significant differences were found in PA, PB1 (65 vs 79 g/kg CP), PB2, and PC fractions (10 vs 33 g/kg CP), indicating protein degradation and supply to small intestine differed between two new lines. In terms of protein structure spectral profile, there were no significant differences in functional groups of amides I and II, α helix, and β-sheet structure as well as their ratio between the two new lines, indicating no difference in protein structure makeup and conformation between the two lines. In terms of energy values, there were significant differences in total digestible nutrient (TDN; 149 vs 133 g/kg DM), metabolizable energy (ME; 58 vs 52 MJ/kg DM), and net energy for lactation (NEL; 42 vs 37 MJ/kg DM) between CS-Y and CS-B lines. For in situ rumen degradation kinetics, the two lines differed in soluble fraction (S; 284 vs 341 g/kg CP), potential degradation fraction (D; 672 vs 590 g/kg CP), and effective degraded organic matter (EDOM; 710 vs 684 g/kg OM), but no difference in degradation rate. CS-Y had higher digestibility of rumen bypass protein in the intestine than CS-B (566 vs 446 g/kg of RUP, P < 0.05). Modeling nutrient supply results showed that microbial protein synthesis (MCP; 148 vs 171 g/kg DM) and rumen protein degraded balance (DPB; 108 vs 127 g/kg DM) were lower in the CS-Y line, but there were no differences in total truly digested protein in small intestine (DVE) and feed milk value (FMV) between the two lines. In conclusion, the new yellow line had different nutritional, chemical, and structural features compared to the black line. CS-Y provided better nutrient utilization and availability.

Natural history of markers of collagen turnover in patients with early diastolic dysfunction and impact of eplerenone

OBJECTIVES: This study was designed to evaluate the impact of eplerenone on collagen turnover in preserved systolic function heart failure (HFPSF).

BACKGROUND: Despite growing interest in abnormal collagen metabolism as a feature of HFPSF with diastolic dysfunction, the natural history of markers of collagen turnover and the impact of selective aldosterone antagonism on this natural history remains unknown.

METHODS: We evaluated 44 patients with HFPSF, randomly assigned to control (n = 20) or eplerenone 25 mg daily (n = 24) for 6 months, increased to 50 mg daily from 6 to 12 months. Serum markers of collagen turnover and inflammation were analyzed at baseline and at 6 and 12 months and included pro-collagen type-I and -III aminoterminal peptides, matrix metalloproteinase type-2, interleukin-6 and -8, and tumor necrosis factor-alpha. Doppler-echocardiographic assessment of diastolic filling indexes and tissue Doppler analyses were also obtained.

RESULTS: The mean age of the patients was 80 +/- 7.8 years; 46% were male; 64% were receiving an angiotensin-converting enzyme inhibitor, 34% an angiotensin-II receptor blocker, and 68% were receiving beta-blocker therapy. Pro-collagen type-III and -I aminoterminal peptides, matrix metalloproteinase type-2, interleukin-6 and -8, and tumor necrosis factor-alpha increased with time in the control group. Eplerenone treatment had no significant impact on any biomarker at 6 months but attenuated the increase in pro-collagen type-III aminoterminal peptide at 12 months (p = 0.006). Eplerenone therapy was associated with modest effects on diastolic function without any impact on clinical variables or brain natriuretic peptide.

CONCLUSIONS: This study demonstrates progressive increases in markers of collagen turnover and inflammation in HFPSF with diastolic dysfunction. Despite high background utilization of renin-angiotensin-aldosterone modulators, eplerenone therapy prevents a progressive increase in pro-collagen type-III aminoterminal peptide and may have a role in management of this disease. (The Effect of Eplerenone and Atorvastatin on Markers of Collagen Turnover in Diastolic Heart Failure; NCT00505336).

DES14X3taz: A Type I Superluminous Supernova Showing a Luminous, Rapidly Cooling Initial Pre-peak Bump

We present DES14X3taz, a new hydrogen-poor superluminous supernova (SLSN-I) discovered by the Dark Energy Survey (DES) supernova program, with additional photometric data provided by the Survey Using DECam for Superluminous Supernovae. Spectra obtained using Optical System for Imaging and low-Intermediate-Resolution Integrated Spectroscopy on the Gran Telescopio CANARIAS show DES14X3taz is an SLSN-I at <i style="margin: 0px; padding: 0px; border: 0px; font-variant-numeric: inherit; font-stretch: inherit; font-size: 18px; line-height: 27px; font-family: minion-pro, Georgia, "Times New Roman", STIXGeneral, serif; vertical-align: baseline; color: rgb(51, 51, 51);">zi> = 0.608. Multi-color photometry reveals a double-peaked light curve: a blue and relatively bright initial peak that fades rapidly prior to the slower rise of the main light curve. Our multi-color photometry allows us, for the first time, to show that the initial peak cools from 22,000 to 8000 K over 15 rest-frame days, and is faster and brighter than any published core-collapse supernova, reaching 30% of the bolometric luminosity of the main peak. No physical 56Ni-powered model can fit this initial peak. We show that a shock-cooling model followed by a magnetar driving the second phase of the light curve can adequately explain the entire light curve of DES14X3taz. Models involving the shock-cooling of extended circumstellar material at a distance of 400  are preferred over the cooling of shock-heated surface layers of a stellar envelope. We compare DES14X3taz to the few double-peaked SLSN-I events in the literature. Although the rise times and characteristics of these initial peaks differ, there exists the tantalizing possibility that they can be explained by one physical interpretation.

Low mating frequency of queens in the stingless bee <i>Scaptotrigona posticai> and worker maternity of males.

Kin selection models of intracolonial conflict over the maternity of males predict that social hymenopteran workers should favour the production of sons and nephews over brothers when the effective mating frequency (me) of the queen is low (me2. Stingless bees have been used to support these models in that me within the group is considered low and workers are thought often to monopolise the parentage of males. We genetically analysed 20 worker and 20 male pupae from each of 10 colonies of the stingless bee Scaptotrigona postica (= Scaptotrigona aff. depilis) using six microsatellite loci and demonstrate queen monandry in eight nests and apparent low me in the other two. However, four colonies contained an additional matriline, possibly due to queen supersedure (serial polygyny), which complicated their genetic structure. Across colonies, workers were responsible for the maternity of 13% of all males. These data are broadly in agreement with predictions from kin selection theory, though the question remains open as to why workers do not secure a greater share of male maternity in this and other stingless bee species in which workers are more closely related to nephews than brothers.

Sediment distribution, hydrolytic enzyme profiles and bacterial activities in the guts of <i>Oneirophanta mutabilisi>, <i>Psychropotes longicaudai> and <i>Pseudostichopusi> - what do they tell us about digestive strategies of abyssal holothurians?

This paper describes inter-specific differences in the distribution of sediment in the gut compartments and in the enzyme and bacterial profiles along the gut of abyssal holothurian species — Oneirophanta mutabilis, Psychropotes longicauda and Pseudostichopus villosus sampled from a eutrophic site in the NE Atlantic at different times of the year. Proportions of sediments, relative to total gut contents, in the pharynx, oesophagus, anterior and posterior intestine differed significantly in all the inter-species comparisons, but not between inter-seasonal comparisons. Significant differences were also found between the relative proportions of sediments in both the rectum and cloaca of Psychropotes longicauda and Oneirophanta mutabilis. Nineteen enzymes were identified in either gut-tissue or gut-content samples of the holothurians studied. Concentrations of the enzymes in gut tissues and their contents were highly correlated. Greater concentrations of the enzymes were found in the gut tissues suggesting that they are the main source of the enzymes. The suites of enzymes recorded were broadly similar in each of the species sampled collected regardless of the time of the year, and they were similar to those described previously for shallow-water holothurians. Significant inter-specific differences in the gut tissue concentrations of some of the glycosidases suggest dietary differences. For example, Psychropotes longicauda and Pseudostichopus villosus contain higher levels of chitobiase than Oneirophanta mutabilis. There were no seasonal changes in bacterial activity profiles along the guts of O. mutabilis and Pseudostichopus villosus. In both these species bacterial activity and abundance declined between the pharynx/oesophagus and anterior intestine, but then increased along the gut and became greatest in the rectum/cloaca. Although the data sets were more limited for Psychropotes longicauda, bacterial activity increased from the anterior to the posterior intestine but then declined slightly to the rectum/cloaca. These changes in bacterial activity and densities probably reflect changes in the microbial environment along the guts of abyssal holothurians. Such changes suggest that there is potential for microbial breakdown of a broader range of substrates than could be otherwise be achieved by the holothurian itself. However, the present study found no evidence for sedimentary (microbial) sources of hydrolytic enzymes.

Endogenous expression and localization of myostatin and its relation to MHC distribution in C2C12 skeletal muscle cells

Myostatin is a negative regulator of skeletal muscle growth. We have previously reported that recombinant myostatin protein inhibits DNA and protein synthesis in C2C12 cells. Our objective was to assess if C2C12 cells express myostatin, determine its sub-cellular localization and the developmental stage of C2C12 cells in which myostatin mRNA and protein are expressed. To study the endogenous expression of myostatin, C2C12 myoblasts were allowed to progress to myotubes, and changes in the levels of endogenous myostatin mRNA expression were determined by RT-PCR. The myostatin protein and the two major myosin heavy chain (MHC) isoforms (MHC-I and -II) were determined by Western blot. Confirmation of the relative MHC expression patterns was obtained by a modified polyacrylamide gel electropheretic (PAGE) procedure. Imunofluorescence staining was employed to localize the site of myostatin expression and the relative distribution of the MHC isoforms. Co-expression of these proteins was studied using a dual staining approach. Expression of myostatin mRNA was found in myotubes but not in myoblasts. Myostatin protein was seen in most but not all, of the nuclei of polynucleated fibers expressing MHC-II, and myostatin was detected in the cytoplasm of myotube. The localization of myostatin protein in myotube nuclei was confirmed by Western blot of isolated nuclear and cytoplasmic fractions. Incubation of C2C12 myotubes with graded doses of dexamethasone dose-dependently increased the intensity of nuclear myostatin immunostaining and also resulted in the appearance of cytoplasmic expression. In conclusion, myostatin was expressed mostly in C2C12 myotubes nuclei expressing MHC-II. Its predominant

Improved Principal Component Monitoring of Large-Scale Processes

This is the first paper that shows and theoretically analyses that the presence of auto-correlation can produce considerable alterations in the Type I and Type II errors in univariate and multivariate statistical control charts. To remove this undesired effect, linear inverse ARMA filter are employed and the application studies in this paper show that false alarms (increased Type I errors) and an insensitive monitoring statistics (increased Type II errors) were eliminated.

Gender influences the detection of spatial working memory deficits in bipolar disorder.

Objective: Despite evidence that gender may influence neurocognitive functioning, few studies have examined its effects in bipolar disorder (BD) a priori. The aim of this study was to examine how gender influences executive-type functions, which are potentially useful as endophenotypes for BD. Methods: The performance of 26 euthymic patients(12 males, 14 females) with DSM-IV BD (20 BD type I and six BD type II) was compared to that of 26 controls (12 males, 14 females) on tests of executive function. Controls were matched to patients on an individual basis for sex, age and premorbid IQ. Tests assessed spatial working memory (SWM), planning, attentional set-shifting and verbal fluency. Results: Overall, patients showed deficits in SWM strategy (p < 0.001) and made more SWM errors relative to controls (p < 0.001). These deficits were more apparent in male-only comparisons (both p < 0.001) than in female-only comparisons (both p < 0.05). When examined in isolation, male controls were significantly better at performing the SWM task than female controls (both p < 0.05). This pattern was not observed in the patient cohort: male patients had poorer strategy scores than female patients (p < 0.05), but made a similar number of SWM errors. Conclusions: These findings provide evidence that gender can influence the detection of SWM deficits in the euthymic phase of BD, as the sex-related disequilibrium in SWM identified in healthy controls was disrupted in BD. © 2008 The Authors Journal compilation © 2008 Blackwell Munksgaard.