Probing the formation of intermediate- to high-mass stars in protoclusters II. Comparison between millimeter interferometric observations of NGC 2264-C and SPH simulations of a collapsing clump

The earliest phases of massive star formation in clusters are still poorly understood. Here, we test the hypothesis for high-mass star formation proposed in our earlier paper (Peretto et al. 2006). In order to confirm the physical validity of this hypothesis, we carried out IRAM Plateau de Bure interferometer observations of NGC 2264-C and performed SPH numerical simulations of the collapse of a Jeans-unstable, prolate dense clump. Our Plateau de Bure observations reveal the presence of a new compact source (C-MM13) located only \~ 10000 AU away, but separated by ~ 1.1 km/s in (projected) velocity, from the most massive Class 0 object (C-MM3) lying at the very center of NGC 2264-C. Detailed comparison with our numerical SPH simulations supports the view that NGC 2264-C is an elongated cluster-forming clump in the process of collapsing and fragmenting along its long axis, leading to a strong dynamical interaction and possible protostar merger in the central region of the clump. The present study also sets several quantitative constraints on the initial conditions of large-scale collapse in NGC 2264-C. Our hydrodynamic simulations indicate that the observed velocity pattern characterizes an early phase of protocluster collapse which survives for an only short period of time (i.e., < 10^5 yr). To provide a good match to the observations the simulations require an initial ratio of turbulent to gravitational energy of only ~ 5 %, which strongly suggests that the NGC 2264-C clump is structured primarily by gravity rather than turbulence. The required "cold'' initial conditions may result from rapid compression by an external trigger.Comment: 15 pages, 8 figures, accepted for publication in A&

Characterization and Regulation of the Osmolyte Betaine Synthesizing Enzymes GSMT and SDMT from Halophilic Methanogen Methanohalophilus portucalensis

The halophilic methanoarchaeon Methanohalophilus portucalensis can synthesize the osmolyte betaine de novo in response to extracellular salt stress. Betaine is generated by the stepwise methylation of glycine to form sarcosine, N, N-dimethylglycine and betaine by using S-adenosyl-L-methionine (AdoMet) as the methyl donor. The complete gene cluster of Mpgsmt-sdmt was cloned from Southern hybridization and heterologous expressed in E. coli respectively. The recombinant MpGSMT and MpSDMT both retained their in vivo functional activities in E. coli BL21(DE3)RIL to synthesize and accumulate betaine and conferred elevated survival ability in betaine transport deficient mutant E. coli MKH13 under high salt stress. The dramatic activating effects of sodium and potassium ions on the in vitro methyltransferase activities of MpGSMT, but not MpSDMT or bacterial GSMT and SDMT, revealed that GSMT from halophilic methanoarchaeon possesses novel regulate mechanism in betaine biosynthesis pathway. The circular dichroism spectra showed the fluctuated peaks at 206 nm were detected in the MpGSMT under various concentrations of potassium or sodium ions. This fluctuated difference may cause by a change in the β-turn structure located at the conserved glycine- and sarcosine-binding residue Arg167 of MpGSMT. The analytical ultracentrifugation analysis indicated that the monomer MpGSMT switched to dimeric form increased from 7.6% to 70% with KCl concentration increased from 0 to 2.0 M. The level of potassium and sodium ions may modulate the substrate binding activity of MpGSMT through the conformational change. Additionally, MpGSMT showed a strong end product, betaine, inhibitory effect and was more sensitive to the inhibitor AdoHcy. The above results indicated that the first enzymatic step involved in synthesizing the osmolyte betaine in halophilic archaea, namely, GSMT, may also play a major role in coupling the salt-in and compatible solute (osmolyte) osmoadaptative strategies in halophilic methanogens for adapting to high salt environments

Supporting data for "CandiMeth: Powerful yet simple visualization and quantification of DNA methylation at candidate genes"

DNA methylation microarrays are widely used in clinical epigenetics and are often processed using R packages like ChAMP or RnBeads by trained bioinformaticians. However, looking at specific genes requires bespoke coding which wet-lab biologists or clinicians are not trained for. This leads to high demands on bioinformaticians, who in turn may lack insight into the specific biological problem. We therefore wished to develop a tool for mapping and quantification of methylation differences at candidate genomic features of interest, without using coding, to bridge this gap. We generated the workflow CandiMeth (CANDIdate METHylation) in the web-based environment Galaxy. CandiMeth takes as input any table listing differences in methylation generated by either of the popular R-based packages above and maps these to the human genome. A simple interface then allows the user to query the data using lists of gene names. CandiMeth generates 1)Tracks in the popular UCSC genome browser with an intuitive visual indicator of where differences in methylation occur between samples, or groups of samples 2) Tables containing quantitative data on the candidate regions, allowing interpretation of significance. In addition to genes and promoters, CandiMeth can analyse methylation differences at LINEs and SINEs. Cross-comparison to other open-resource genomic data at UCSC facilitates interpretation of the biological significance of the data and the design of wet lab assays to further explore methylation changes and their consequences for the candidate genes. CandiMeth (RRID:SCR_017974; Biotools:CandiMeth) allows rapid, quantitative analysis of methylation at user-specified features without the need for coding and is freely available, with extensive guidance, at CandiMeth GitHub repo

Probing the formation of intermediate- to high-mass stars in protoclusters: A detailed millimeter study of the NGC 2264 clumps

We present the results of dust continuum and molecular line observations of two massive cluster-forming clumps, NGC 2264-C and NGC 2264-D, including extensive mapping performed with the MAMBO bolometer array and the HERA heterodyne array on the IRAM 30m telescope. Both NGC 2264 clumps are located in the Mon OB1 giant molecular cloud complex, adjacent to one another. Twelve and fifteen compact millimeter continuum sources (i.e. MMSs) are identified in clumps C and D, respectively. Evidence for widespread infall motions is found in, e.g., HCO+(3-2) or CS(3-2) in both NGC 2264-C and NGC 2264-D. A sharp velocity discontinuity ~ 2 km/s in amplitude is observed in N_2H+(1-0) and H^{13}CO+(1-0) in the central, innermost part of NGC 2264-C, which we interpret as the signature of a strong dynamical interaction between two MMSs and their possible merging with the central MMS C-MM3. Radiative transfer modelling supports the idea that NGC 2264-C is a highly unstable prolate clump in the process of collapsing along its long axis on a near free-fall dynamical timescale ~ 1.7x10^5 yr. Our model fit of this large-scale collapse suggests a maximum mass inflow rate ~ 3x10^{-3} Msun/yr toward the central protostellar object C-MM3. Such infall rates are sufficiently high to overcome radiation pressure and allow the formation of ~ 20 Msun stars by accretion in ~ 1.7x10^5 yr, i.e., a time similar to the global dynamical timescale of the central part of NGC 2264-C. We conclude that we are likely witnessing the formation of a high-mass (> 10 Msun) protostar in the central part of NGC 2264-C. Our results suggest a picture of massive star formation intermediate between the scenario of stellar mergers of Bonnell et al. (1998) and the massive turbulent core model of McKee & Tan (2003).Comment: 22 pages, 16 figures, accepted for publication in A&A. Most of the Figures have been de-resolved in order to reduce file size

The Formation of the First Massive Black Holes

Supermassive black holes (SMBHs) are common in local galactic nuclei, and SMBHs as massive as several billion solar masses already exist at redshift z=6. These earliest SMBHs may grow by the combination of radiation-pressure-limited accretion and mergers of stellar-mass seed BHs, left behind by the first generation of metal-free stars, or may be formed by more rapid direct collapse of gas in rare special environments where dense gas can accumulate without first fragmenting into stars. This chapter offers a review of these two competing scenarios, as well as some more exotic alternative ideas. It also briefly discusses how the different models may be distinguished in the future by observations with JWST, (e)LISA and other instruments.Comment: 47 pages with 306 references; this review is a chapter in "The First Galaxies - Theoretical Predictions and Observational Clues", Springer Astrophysics and Space Science Library, Eds. T. Wiklind, V. Bromm & B. Mobasher, in pres

Cancer risk in hospitalised asthma patients

Asthma is an increasingly common disorder, affecting 5–10% of the population. It involves a dysregulated immune function, which may predispose to subsequent cancer. We examined cancer risk among Swedish subjects who had hospital admission once or multiple times for asthma. An asthma research database was created by identifying asthma patients from the Swedish Hospital Discharge Register and by linking them with the Cancer Registry. A total of 140 425 patients were hospitalised for asthma during 1965–2004, of whom 7421 patients developed cancer, giving an overall standardised incidence ratio (SIR) of 1.36. A significant increase was noted for most sites, with the exception of breast and ovarian cancers and non-Hodgkin's lymphoma and myeloma. Patients with multiple hospital admissions showed a high risk, particularly for stomach (SIR 1.70) and colon (SIR 1.99) cancers. A significant decrease was noted for endometrial cancer and skin melanoma. Oesophageal and lung cancers showed high risks throughout the study period, whereas stomach cancer increased towards the end of the period. The relatively stable temporal trends suggest that the asthmatic condition rather than its medication is responsible for the observed associations

Asian-Specific total knee system: 5-14 year follow-up study

<p>Abstract</p> <p>Background</p> <p>Knee size and body size differ in Asians compared with Caucasians. Nevertheless, many total knee arthroplasty (TKA) prostheses used worldwide are made for Western Caucasian subjects. As a result, an Asian's knee might not fit these prostheses. We studied the Flexible Nichidai Knee (FNK) system, a new model of TKA for Asian patients. The purpose of this report is to investigate the outcomes of this prosthesis retrospectively.</p> <p>Methods</p> <p>We investigated 1055 primary TKAs in 595 patients who underwent FNK for osteoarthritis (OA) in Japan and were followed for > 5 years. The knee score and function score were used for clinical evaluation. We examined the range of motion (ROM) preoperatively and at final follow-up and radiographic assessments. In addition, postoperative complications were investigated. A survivorship analysis was also conducted using two endpoints: revision for any reason and aseptic failure.</p> <p>Results</p> <p>890 knees in 502 patients were available for study (follow-up rate of 96.0%). The mean follow-up term was 8.3 years (range, 5.0-14.1 years). The knee and function score significantly improved from 41.3 to 90.3 and from 39.1 to 76.2 points, respectively (p < 0.001). The mean ROM in FNK posterior cruciate retaining (CR) type and FNK posterior-stabilized (PS) type ameliorated significantly from 107.8° and 95.6° to 110.7° and 110.4°, respectively (p < 0.01). Ten knees underwent revision surgery (infection in 3 cases, instability in 2, loosening in 2, and non-union of femoral supracondylar fracture, severe pain, and recurrent hemarthrosis in 1 each). The survivorship rate was 99.4% (95% CI, 99.0-99.8) at 5 years (n = 952 patients at risk) and 96.2% (95% CI, 91.9-100) at 12.5 years (n = 49 patients at risk).</p> <p>Conclusion</p> <p>The FNK prosthesis for Asians achieved excellent mid- to long-term survivorship and clinical results.</p

Distinct distribution and prognostic significance of molecular subtypes of breast cancer in Chinese women: a population-based cohort study

<p>Abstract</p> <p>Background</p> <p>Molecular classification of breast cancer is an important prognostic factor. The distribution of molecular subtypes of breast cancer and their prognostic value has not been well documented in Asians.</p> <p>Methods</p> <p>A total of 2,791 breast cancer patients recruited for a population-based cohort study were evaluated for molecular subtypes of breast cancer by immunohistochemical assays. Data on clinicopathological characteristics were confirmed by centralized pathology review. The average follow-up of the patients was 53.4 months. Overall and disease-free survival by molecular subtypes of breast cancer were evaluated.</p> <p>Results</p> <p>The prevalence of the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and triple-negative subtypes were 48.6%, 16.7%, 13.7%, and 12.9%, respectively. The luminal A subtype was more likely to be diagnosed in older women (P = 0.03) and had a stronger correlation with favorable clinicopathological factors (smaller tumor size, lower histologic grade, and earlier TNM stage) than the triple-negative or HER2 subtypes. Women with triple-negative breast cancer had a higher frequency of family history of breast cancer than women with other subtypes (P = 0.048). The 5-year overall/disease-free survival percentages for the luminal A, luminal B, HER2, and triple-negative subtypes were 92.9%/88.6%, 88.6%/85.1%, 83.2%/79.1%, and 80.7%/76.0%, respectively. A similar pattern was observed in multivariate analyses. Immunotherapy was associated with improved overall and disease-free survival for luminal A breast cancer, but reduced disease-free survival (HR = 2.21, 95% CI, 1.09-4.48) for the HER2 subtype of breast cancer.</p> <p>Conclusions</p> <p>The triple-negative and HER2 subtypes were associated with poorer outcomes compared with the luminal A subtype among these Chinese women. The HER2 subtype was more prevalent in this Chinese population compared with Western populations, suggesting the importance of standardized HER2 detection and anti-HER2 therapy to potentially benefit a high proportion of breast cancer patients in China.</p