Raising the Dead: Clues to Type Ia Supernova Physics from the Remnant 0509-67.5

We present Chandra X-ray observations of the young supernova remnant (SNR) 0509-67.5 in the Large Magellanic Cloud (LMC), believed to be the product of a Type Ia supernova (SN Ia). The remnant is very round in shape, with a distinct clumpy shell-like structure. Our Chandra data reveal the remnant to be rich in silicon, sulfur, and iron. The yields of our fits to the global spectrum confirm that 0509-67.5 is the remnant of an SN Ia and show a clear preference for delayed detonation explosion models for SNe Ia. We study the spectrum of the single brightest isolated knot in the remnant and find that it is enhanced in iron by a factor of roughly two relative to the global remnant abundances. This feature, along with similar knots seen in Tycho's SNR, argues for the presence of modest small-scale composition inhomogeneities in SNe Ia. The presence of both Si and Fe, with abundance ratios that vary from knot to knot, indicates that these came from the transition region between the Si- and Fe-rich zones in the exploded star, possibly as a result of energy input to the ejecta at late times due to the radioactive decay of 56Ni and 56Co. Two cases for the continuum emission from the global spectrum were modeled: one where the continuum is dominated by hydrogen thermal bremsstrahlung radiation; another where the continuum arises from non-thermal synchrotron radiation. The former case requires a relatively large value for the ambient density (~1 cm^-3). Another estimate of the ambient density comes from using the shell structure of the remnant in the context of dynamical models. This requires a much lower value for the density (<0.05 cm^-3) which is more consistent with other evidence known about 0509-67.5. We therefore conclude that the bulk of the continuum emission from 0509-67.5 has a non-thermal origin.Comment: 34 pages, 9 figures (1 color), accepted to ApJ (10 June 2004 issue); correction made to calculation of magnetic field, small sentence change

Stress rapidly suppresses in vivo LH pulses and increases activation of RFRP-3 neurons in male mice

Restraint stress is a psychosocial stressor that suppresses reproductive status, including LH pulsatile secretion, but the neuroendocrine mechanisms underlying this inhibition remains unclear. Reproductive neural populations upstream of gonadotropin-releasing hormone (GnRH) neurons, such as kisspeptin, neurokinin B and RFRP-3 (GnIH) neurons, are possible targets for psychosocial stress to inhibit LH pulses, but this has not been well examined, especially in mice in which prior technical limitations prevented assessment of in vivo LH pulse secretion dynamics. Here, we examined whether one-time acute restraint stress alters in vivo LH pulsatility and reproductive neural populations in male mice, and what the time-course is for such alterations. We found that endogenous LH pulses in castrated male mice are robustly and rapidly suppressed by one-time, acute restraint stress, with suppression observed as quickly as 12–18 min. This rapid LH suppression parallels with increased in vivo corticosterone levels within 15 min of restraint stress. Although Kiss1, Tac2 and Rfrp gene expression in the hypothalamus did not significantly change after 90 or 180 min restraint stress, arcuate Kiss1 neural activation was significantly decreased after 180 min. Interestingly, hypothalamic Rfrp neuronal activation was strongly increased at early times after restraint stress initiation, but was attenuated to levels lower than controls by 180 min of restraint stress. Thus, the male neuroendocrine reproductive axis is quite sensitive to short-term stress exposure, with significantly decreased pulsatile LH secretion and increased hypothalamic Rfrp neuronal activation occurring rapidly, within minutes, and decreased Kiss1 neuronal activation also occurring after longer stress durations

Detection of Magnesium-Rich Ejecta in the Middle-Aged Supernova Remnant N49B

The middle-aged supernova remnant (SNR) N49B in the Large Magellanic Cloud has been observed with the {\it Chandra X-Ray Observatory}. The superb angular resolution of {\it Chandra} resolves the complex structure of X-ray emitting filaments across the SNR. All observed features are soft ($E <$ 3 keV) and we find no evidence for either point-like or extended hard emission within the SNR. Spectral lines from O, Ne, Mg, Si, S, and Fe are present. Equivalent width images for the detected elemental species and spatially-resolved spectral analysis reveal the presence of Mg-rich ejecta within the SNR. We find no such enrichment in O or Ne, which may reflect details of the nucleosynthesis process or the heating and cooling of the ejecta as it evolved. The bright circumferential filaments are emission from the shocked dense interstellar medium (ISM). We detect faint diffuse X-ray emission that extends beyond the X-ray bright filaments toward the west and southeast. These features appear to be the blast wave shock front expanding into lower density portions of the ISM seen in projection. We set an upper limit of $\sim$$2\times 10^{33}$ ergs s$^{-1}$ on the 0.5 $-$ 5 keV band X-ray luminosity of any embedded compact object.Comment: 3 text pages (ApJ emulator style), 3 figures, 1 table, Accepted for the publication in Ap J Letter

Utilizing a Combined Approach to Assess the Antimicrobial Efficacy of Peracetic Acid on Chicken Thighs and Beef Trim

Antimicrobial interventions are widely utilized in the meat and poultry industry as a way to reduce foodborne pathogens; however, little is known about their overall impact on the microbiota. The objective of this study was to evaluate the impact of peracetic acid (PAA), when used as a short-duration antimicrobial spray, on the pathogen load and microbiota of inoculated chicken thighs and beef trim. Thighs were inoculated with a cocktail of Salmonella spp. and Campylobacter jejuni and trim with a cocktail of Salmonella spp. and Shiga toxin-producing Escherichia coli (E. coli). Inoculated thighs and trim were either not treated (NT) or independently sprayed in a modified spray cabinet with one of the following treatments: 0, 200, 400, and 800 ppm PAA. Samples were rinsed and subsequently used for pathogen detection and microbiota analyses. Pathogens were enumerated by spread plating on selective media, and genomic DNA was extracted for 16S rRNA gene sequencing. Pathogen data were analyzed using ANOVA and linear regression, with means separated by Tukey’s Protected honestly significant differences (HSD; P≤0.05). Microbiota data were analyzed using the QIIME2 pipeline, with data considered significant at P≤0.05 for main effects and Q≤0.05 for pairwise differences. Results from this study demonstrate that a spray, with and without PAA, effectively lowered the level of pathogens compared to NT (P&lt;0.05). Increasing PAA concentrations resulted in lower levels of Salmonella and Campylobacter on thighs (P&lt;0.05, R2=0.44 and 0.55) and Salmonella and E. coli on trim (P&lt;0.05, R2=0.18 and 0.17). The microbiota remained mostly unchanged, with pairwise differences being observed between 0 and 400 ppm and 0 and 800 ppm (P&lt;0.05 Q&lt;0.05) on the β-diversity metric Bray Curtis. The application of PAA as a short-duration antimicrobial spray is an effective intervention strategy to reduce pathogen load; however, efficacy may vary between meat product and target pathogen

Definition of the σW regulon of Bacillus subtilis in the absence of stress

Bacteria employ extracytoplasmic function (ECF) sigma factors for their responses to environmental stresses. Despite intensive research, the molecular dissection of ECF sigma factor regulons has remained a major challenge due to overlaps in the ECF sigma factor-regulated genes and the stimuli that activate the different ECF sigma factors. Here we have employed tiling arrays to single out the ECF σW regulon of the Gram-positive bacterium Bacillus subtilis from the overlapping ECF σX, σY, and σM regulons. For this purpose, we profiled the transcriptome of a B. subtilis sigW mutant under non-stress conditions to select candidate genes that are strictly σW-regulated. Under these conditions, σW exhibits a basal level of activity. Subsequently, we verified the σW-dependency of candidate genes by comparing their transcript profiles to transcriptome data obtained with the parental B. subtilis strain 168 grown under 104 different conditions, including relevant stress conditions, such as salt shock. In addition, we investigated the transcriptomes of rasP or prsW mutant strains that lack the proteases involved in the degradation of the σW anti-sigma factor RsiW and subsequent activation of the σW-regulon. Taken together, our studies identify 89 genes as being strictly σW-regulated, including several genes for non-coding RNAs. The effects of rasP or prsW mutations on the expression of σW-dependent genes were relatively mild, which implies that σW-dependent transcription under non-stress conditions is not strictly related to RasP and PrsW. Lastly, we show that the pleiotropic phenotype of rasP mutant cells, which have defects in competence development, protein secretion and membrane protein production, is not mirrored in the transcript profile of these cells. This implies that RasP is not only important for transcriptional regulation via σW, but that this membrane protease also exerts other important post-transcriptional regulatory functions

The pesticidal Cry6Aa toxin from Bacillus thuringiensis is structurally similar to HlyE-family alpha pore-forming toxins

Background The Cry6 family of proteins from Bacillus thuringiensis represents a group of powerful toxins with great potential for use in the control of coleopteran insects and of nematode parasites of importance to agriculture. These proteins are unrelated to other insecticidal toxins at the level of their primary sequences and the structure and function of these proteins has been poorly studied to date. This has inhibited our understanding of these toxins and their mode of action, along with our ability to manipulate the proteins to alter their activity to our advantage. To increase our understanding of their mode of action and to facilitate further development of these proteins we have determined the structure of Cry6Aa in protoxin and trypsin-activated forms and demonstrated a pore-forming mechanism of action. Results The two forms of the toxin were resolved to 2.7 Å and 2.0 Å respectively and showed very similar structures. Cry6Aa shows structural homology to a known class of pore-forming toxins including hemolysin E from Escherichia coli and two Bacillus cereus proteins: the hemolytic toxin HblB and the NheA component of the non-hemolytic toxin (pfam05791). Cry6Aa also shows atypical features compared to other members of this family, including internal repeat sequences and small loop regions within major alpha helices. Trypsin processing was found to result in the loss of some internal sequences while the C-terminal region remains disulfide-linked to the main core of the toxin. Based on the structural similarity of Cry6Aa to other toxins, the mechanism of action of the toxin was probed and its ability to form pores in vivo in Caenorhabditis elegans was demonstrated. A non-toxic mutant was also produced, consistent with the proposed pore-forming mode of action. Conclusions Cry6 proteins are members of the alpha helical pore-forming toxins – a structural class not previously recognized among the Cry toxins of B. thuringiensis and representing a new paradigm for nematocidal and insecticidal proteins. Elucidation of both the structure and the pore-forming mechanism of action of Cry6Aa now opens the way to more detailed analysis of toxin specificity and the development of new toxin variants with novel activities

DNA methylation-based classification of glioneuronal tumours synergises with histology and radiology to refine accurate molecular stratification

AIMS: Glioneuronal tumours (GNTs) are poorly distinguished by their histology and lack robust diagnostic indicators. Previously, we showed that common GNTs comprise two molecularly distinct groups, correlating poorly with histology. To refine diagnosis, we constructed a methylation-based model for GNT classification, subsequently evaluating standards for molecular stratification by methylation, histology and radiology. METHODS: We comprehensively analysed methylation, radiology and histology for 83 GNT samples: a training cohort of 49, previously classified into molecularly defined groups by genomic profiles, plus a validation cohort of 34. We identified histological and radiological correlates to molecular classification and constructed a methylation-based support vector machine (SVM) model for prediction. Subsequently, we contrasted methylation, radiological and histological classifications in validation GNTs. RESULTS: By methylation clustering, all training and 23/34 validation GNTs segregated into two groups, the remaining 11 clustering alongside control cortex. Histological review identified prominent astrocytic/oligodendrocyte-like components, dysplastic neurons, and a specific glioneuronal element as discriminators between groups. However, these were present in only a subset of tumours. Radiological review identified location, margin definition, enhancement, and T2 FLAIR-rim sign as discriminators. When validation GNTs were classified by SVM, 22/23 classified correctly, comparing favourably against histology and radiology which resolved 17/22 and 15/21 respectively where data were available for comparison. CONCLUSIONS: Diagnostic criteria inadequately reflect glioneuronal tumour biology, leaving a proportion unresolvable. In the largest cohort of molecularly defined glioneuronal tumours, we develop molecular, histological, and radiological approaches for biologically meaningful classification and demonstrate almost all cases are resolvable, emphasising the importance of an integrated diagnostic approach

Timing of the decline in physical activity in childhood and adolescence : Gateshead Millennium Cohort Study

Background and Aim: There is a widely held and influential view that physical activity begins to decline at adolescence. This study aimed to identify the timing of changes in physical activity during childhood and adolescence. Methods: Longitudinal cohort study (Gateshead Millennium Study) with eight years of follow-up, from Northeast England. Cohort members comprise a socioeconomically representative sample studied at ages 7, 9, 12 and 15 years; 545 individuals provided physical activity data at two or more time points. Habitual total volume of physical activity and moderate-to-vigorous intensity physical activity (MVPA) were quantified objectively using the Actigraph accelerometer over 5-7 days at the four time points. Linear mixed models identified the timing of changes in physical activity across the 8 year period, and trajectory analysis was used to identify sub-groups with distinct patterns of age-related changes. Results: Four trajectories of change in total volume of physical activity were identified representing 100% of all participants: all trajectories declined from age 7. There was no evidence that physical activity decline began at adolescence, or that adolescent declines in physical activity were substantially greater than the declines during childhood, or greater in girls than boys. One group (19% of boys) had relatively high MVPA which remained stable between ages 7-15 years. Conclusions: Future policy and research efforts to promote physical activity should begin well before adolescence, and should include both boys and girls

Patient-reported outcome instruments for assessing Raynaud’s phenomenon in systemic sclerosis:A SCTC vascular working group report

The episodic nature of Raynaud’s phenomenon in systemic sclerosis has led to a reliance on patient-reported outcome instruments such as the Raynaud’s Condition Score diary. Little is known about the utilization in routine clinical practice and health professional attitudes toward existing patient-reported outcome instruments for assessing systemic sclerosis- Raynaud’s phenomenon. Members of the Scleroderma Clinical Trials Consortium Vascular Working Group (n = 28) were invited to participate in a survey gauging attitudes toward the Raynaud’s Condition Score diary and the perceived need for novel patient-reported outcome instruments for assessing patient-reported outcome. Nineteen Scleroderma Clinical Trials Consortium Vascular Working Group members (68% response rate) from academic units based in North America (n = 9), Europe (n = 8), South America (n = 1) and Australasia (n = 1) took part in the survey. There was broad consensus that Raynaud’s Condition Score diary returns could be influenced by factors including seasonal variation in weather, efforts made by patients to avoid or ameliorate attacks of Raynaud’s phenomenon, habituation to Raynaud’s phenomenon symptoms, evolution of Raynaud’s phenomenon symptom characteristics with progressive obliterative microangiopathy, patient-coping strategies, respondent burden and placebo effect. There was consensus that limitations of the Raynaud’s Condition Score diary might be a barrier to drug development (79% of respondents agree/strongly agree) and that a novel patient-reported outcome instrument for assessing systemic sclerosis-Raynaud’s phenomenon should be developed with the input of both clinicians and patients (84% agree/strongly agree). Perceived potential limitations of the Raynaud’s Condition Score diary have been identified along with concerns that such factors might impede drug development programs for systemic sclerosis-Raynaud’s phenomenon. There is support within the systemic sclerosis community for the development of a novel patient-reported outcome instrument for assessing systemic sclerosis-Raynaud’s phenomenon.</p