Density distributions, magnetic field structures and fragmentation in high-mass star formation

Methods: Observing the large pc-scale Stokes I mm dust continuum emission with the IRAM 30m telescope and the intermediate-scale (<0.1pc) polarized submm dust emission with the Submillimeter Array toward a sample of 20 high-mass star-forming regions allows us to quantify the dependence of the fragmentation behaviour of these regions depending on the density and magnetic field structures. Results: We infer density distributions n~r^{-p} of the regions with typical power-law slopes p around ~1.5. There is no obvious correlation between the power-law slopes of the density structures on larger clump scales (~1pc) and the number of fragments on smaller core scales (<0.1pc). Comparing the large-scale single-dish density profiles to those derived earlier from interferometric observations at smaller spatial scales, we find that the smaller-scale power-law slopes are steeper, typically around ~2.0. The flattening toward larger scales is consistent with the star-forming regions being embedded in larger cloud structures that do not decrease in density away from a particular core. Regarding the magnetic field, for several regions it appears aligned with filamentary structures leading toward the densest central cores. Furthermore, we find different polarization structures with some regions exhibiting central polarization holes whereas other regions show polarized emission also toward the central peak positions. Nevertheless, the polarized intensities are inversely related to the Stokes I intensities. We estimate magnetic field strengths between ~0.2 and ~4.5mG, and we find no clear correlation between magnetic field strength and the fragmentation level of the regions. Comparison of the turbulent to magnetic energies shows that they are of roughly equal importance in this sample. The mass-to-flux ratios range between ~2 and ~7, consistent with collapsing star-forming regions.Comment: Accepted for Astronomy & Astrophysics, 14 pages, 14 figures plus appendices, also download option at https://www2.mpia-hd.mpg.de/homes/beuther/papers.htm

JWST Observations of Young protoStars (JOYS+): Detection of icy complex organic molecules and ions. I. CH4_4, SO2_2, HCOO−^-, OCN−^-, H2_2CO, HCOOH, CH3_3CH2_2OH, CH3_3CHO, CH3_3OCHO, CH3_3COOH

Complex organic molecules (COMs) detected in the gas phase are thought to be mostly formed on icy grains, but no unambiguous detection of icy COMs larger than CH3OH has been reported so far. Exploring this matter in more detail has become possible with the JWST the critical 5-10 $\mu$m range. In the JOYS+ program, more than 30 protostars are being observed with the MIRI/MRS. This study explores the COMs ice signatures in the low and high-mass protostar, IRAS 2A and IRAS 23385, respectively. We fit continuum and silicate subtracted observational data with IR laboratory ice spectra. We use the ENIIGMA fitting tool to find the best fit between the lab data and the observations and to performs statistical analysis of the solutions. We report the best fits for the spectral ranges between 6.8 and 8.6 $\mu$m in IRAS 2A and IRAS 23385, originating from simple molecules, COMs, and negative ions. The strongest feature in this range (7.7 $\mu$m) is dominated by CH4 and has contributions of SO2 and OCN-. Our results indicate that the 7.2 and 7.4 $\mu$m bands are mostly dominated by HCOO-. We find statistically robust detections of COMs based on multiple bands, most notably CH3CHO, CH3CH2OH, and CH3OCHO. The likely detection of CH3COOH is also reported. The ice column density ratios between CH3CH2OH and CH3CHO of IRAS 2A and IRAS 23385, suggests that these COMs are formed on icy grains. Finally, the derived ice abundances for IRAS 2A correlate well with those in comet 67P/GC within a factor of 5. Based on the MIRI/MRS data, we conclude that COMs are present in interstellar ices, thus providing additional proof for a solid-state origin of these species in star-forming regions. The good correlation between the ice abundances in comet 67P and IRAS 2A is in line with the idea that cometary COMs can be inherited from the early protostellar phases.Comment: Accepted for publication in A&

Postdiagnosis dietary factors, supplement use and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis

Little is known about how diet might influence breast cancer prognosis. The current systematic reviews and meta-analyses summarise the evidence on postdiagnosis dietary factors and breast cancer outcomes from randomised controlled trials and longitudinal observational studies. PubMed and Embase were searched through 31st October 2021. Random-effects linear dose-response meta-analysis was conducted when at least three studies with sufficient information were available. The quality of the evidence was evaluated by an independent Expert Panel. We identified 108 publications. No meta-analysis was conducted for dietary patterns, vegetables, wholegrains, fish, meat, and supplements due to few studies, often with insufficient data. Meta-analysis was only possible for all-cause mortality with dairy, isoflavone, carbohydrate, dietary fibre, alcohol intake and serum 25-hydroxyvitamin D (25(OH)D), and for breast cancer-specific mortality with fruit, dairy, carbohydrate, protein, dietary fat, fibre, alcohol intake and serum 25(OH)D. The results, with few exceptions, were generally null. There was limited-suggestive evidence that predefined dietary patterns may reduce the risk of all-cause and other causes of death; that isoflavone intake reduces the risk of all-cause mortality (relative risk (RR) per 2 mg/day: 0.96, 95% confidence interval (CI): 0.92-1.02), breast cancer-specific mortality (RR for high vs low: 0.83, 95% CI: 0.64-1.07), and recurrence (RR for high vs low: 0.75, 95% CI: 0.61-0.92); that dietary fibre intake decreases all-cause mortality (RR per 10 g/day: 0.87, 95% CI: 0.80-0.94); and that serum 25(OH)D is inversely associated with all-cause and breast cancer-specific mortality (RR per 10 nmol/L: 0.93, 95% CI: 0.89-0.97 and 0.94, 95% CI: 0.90-0.99, respectively). The remaining associations were graded as limited-no conclusion

Postdiagnosis body fatness, weight change and breast cancer prognosis: Global Cancer Update Program (CUP global) systematic literature review and meta-analysis

Previous evidence on postdiagnosis body fatness and mortality after breast cancer was graded as limited-suggestive. To evaluate the evidence on body mass index (BMI), waist circumference, waist-hip-ratio and weight change in relation to breast cancer prognosis, an updated systematic review was conducted. PubMed and Embase were searched for relevant studies published up to 31 October, 2021. Random-effects meta-analyses were conducted to estimate summary relative risks (RRs). The evidence was judged by an independent Expert Panel using pre-defined grading criteria. One randomized controlled trial and 225 observational studies were reviewed (220 publications). There was strong evidence (likelihood of causality: probable) that higher postdiagnosis BMI was associated with increased all-cause mortality (64 studies, 32 507 deaths), breast cancer-specific mortality (39 studies, 14 106 deaths) and second primary breast cancer (11 studies, 5248 events). The respective summary RRs and 95% confidence intervals per 5 kg/m2 BMI were 1.07 (1.05-1.10), 1.10 (1.06-1.14) and 1.14 (1.04-1.26), with high between-study heterogeneity (I2 = 56%, 60%, 66%), but generally consistent positive associations. Positive associations were also observed for waist circumference, waist-hip-ratio and all-cause and breast cancer-specific mortality. There was limited-suggestive evidence that postdiagnosis BMI was associated with higher risk of recurrence, nonbreast cancer deaths and cardiovascular deaths. The evidence for postdiagnosis (unexplained) weight or BMI change and all outcomes was graded as limited-no conclusion. The RCT showed potential beneficial effect of intentional weight loss on disease-free-survival, but more intervention trials and well-designed observational studies in diverse populations are needed to elucidate the impact of body composition and their changes on breast cancer outcomes

Postdiagnosis recreational physical activity and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis

It is important to clarify the associations between modifiable lifestyle factors such as physical activity and breast cancer prognosis to enable the development of evidence-based survivorship recommendations. We performed a systematic review and meta-analyses to summarise the evidence on the relationship between postbreast cancer diagnosis physical activity and mortality, recurrence and second primary cancers. We searched PubMed and Embase through 31st October 2021 and included 20 observational studies and three follow-up observational analyses of patients enrolled in clinical trials. In linear dose-response meta-analysis of the observational studies, each 10-unit increase in metabolic equivalent of task (MET)-h/week higher recreational physical activity was associated with 15% and 14% lower risk of all-cause (95% confidence interval [CI]: 8%-22%, studies = 12, deaths = 3670) and breast cancer-specific mortality (95% CI: 4%-23%, studies = 11, deaths = 1632), respectively. Recreational physical activity was not associated with breast cancer recurrence (HR = 0.97, 95% CI: 0.91-1.05, studies = 6, deaths = 1705). Nonlinear dose-response meta-analyses indicated 48% lower all-cause and 38% lower breast cancer-specific mortality with increasing recreational physical activity up to 20 MET-h/week, but little further reduction in risk at higher levels. Predefined subgroup analyses across strata of body mass index, hormone receptors, adjustment for confounders, number of deaths, menopause and physical activity intensities were consistent in direction and magnitude to the main analyses. Considering the methodological limitations of the included studies, the independent Expert Panel concluded ‘limited-suggestive’ likelihood of causality for an association between recreational physical activity and lower risk of all-cause and breast cancer-specific mortality

Density distributions, magnetic field structures, and fragmentation in high-mass star formation

[Context] The fragmentation of high-mass star-forming regions depends on a variety of physical parameters, including density, the magnetic field, and turbulent gas properties.[Aims] We evaluate the importance of the density and magnetic field structures in relation to the fragmentation properties during high-mass star formation.[Results] Based on the IRAM 30 m data, we infer density distributions n ∝ r−p of the regions with typical power-law slopes p around ~1.5. There is no obvious correlation between the power-law slopes of the density structures on larger clump scales (~1 pc) and the number of fragments on smaller core scales (<0.1 pc). Comparing the large-scale single-dish density profiles to those derived earlier from interferometric observations at smaller spatial scales, we find that the smaller-scale power-law slopes are steeper, typically around ~2.0. The flattening toward larger scales is consistent with the star-forming regions being embedded in larger cloud structures that do not decrease in density away from a particular core. The magnetic fields of several regions appear to be aligned with filamentary structures that lead toward the densest central cores. Furthermore, we find different polarization structures; some regions exhibit central polarization holes, whereas other regions show polarized emission also toward the central peak positions. Nevertheless, the polarized intensities are inversely related to the Stokes I intensities, following roughly a power-law slope of ∝ SI−0.62. We estimate magnetic field strengths between ~0.2 and ~4.5 mG, and we find no clear correlation between magnetic field strength and the fragmentation level of the regions. A comparison of the turbulent to magnetic energies shows that they are of roughly equal importance in this sample. The mass-to-flux ratios range between ~2 and ~7, consistent with collapsing star-forming regions.[Conclusions] Finding no clear correlations between the present-day large-scale density structure, the magnetic field strength, and the smaller-scale fragmentation properties of the regions, indicates that the fragmentation of high-mass star-forming regions may not be affected strongly by the initial density profiles and magnetic field properties. However, considering the limited evolutionary range and spatial scales of the presented CORE analysis, future research directions should include density structure analysis of younger regions that better resemble the initial conditions, as well as connecting the observed intermediate-scale magnetic field structure with the larger-scale magnetic fields of the parental molecular clouds.R.K. acknowledges financial support via the Heisenberg Research Grant funded by the German Research Foundation (DFG) under grant no. KU 2849/9. A.P. is grateful to Gilberto Gómez and Enrique Vázquez-Semadeni for very insightful discussions. A.P. acknowledges financial support from the UNAM-PAPIIT IG100223 grant, the Sistema Nacional de Investigadores of CONAHCyT, and from the CONAHCyT project number 86372 of the ‘Ciencia de Frontera 2019’ program, entitled ‘Citlalcóatl: a multiscale study at the new frontier of the formation and early evolution of stars and planetary systems’, México. A.S.M. acknowledges support from the RyC2021-032892-I and PID2020-117710GB-I00 grants funded by MCIN/AEI/10.13039/501100011033 and by the European Union ‘NextGenerationEU’/PRTR, as well as the program Unidad de Excelencia María de Maeztu CEX2020-001058-M. J.D.S. acknowledges funding by the European Research Council via the ERC Synergy Grant “ECOGAL – Understanding our Galactic ecosystem: From the disk of the Milky Way to the formation sites of stars and planets” (project ID 855130).With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2020-001058-M).Peer reviewe

Transcriptional Regulation of Rod Photoreceptor Homeostasis Revealed by In Vivo NRL Targetome Analysis

A stringent control of homeostasis is critical for functional maintenance and survival of neurons. In the mammalian retina, the basic motif leucine zipper transcription factor NRL determines rod versus cone photoreceptor cell fate and activates the expression of many rod-specific genes. Here, we report an integrated analysis of NRL-centered gene regulatory network by coupling chromatin immunoprecipitation followed by high-throughput sequencing (ChIP–Seq) data from Illumina and ABI platforms with global expression profiling and in vivo knockdown studies. We identified approximately 300 direct NRL target genes. Of these, 22 NRL targets are associated with human retinal dystrophies, whereas 95 mapped to regions of as yet uncloned retinal disease loci. In silico analysis of NRL ChIP–Seq peak sequences revealed an enrichment of distinct sets of transcription factor binding sites. Specifically, we discovered that genes involved in photoreceptor function include binding sites for both NRL and homeodomain protein CRX. Evaluation of 26 ChIP–Seq regions validated their enhancer functions in reporter assays. In vivo knockdown of 16 NRL target genes resulted in death or abnormal morphology of rod photoreceptors, suggesting their importance in maintaining retinal function. We also identified histone demethylase Kdm5b as a novel secondary node in NRL transcriptional hierarchy. Exon array analysis of flow-sorted photoreceptors in which Kdm5b was knocked down by shRNA indicated its role in regulating rod-expressed genes. Our studies identify candidate genes for retinal dystrophies, define cis-regulatory module(s) for photoreceptor-expressed genes and provide a framework for decoding transcriptional regulatory networks that dictate rod homeostasis

Fragmentation and disk formation during high-mass star formation. IRAM NOEMA (Northern Extended Millimeter Array) large program CORE

Context. High-mass stars form in clusters, but neither the early fragmentation processes nor the detailed physical processes leading to the most massive stars are well understood. Aims. We aim to understand the fragmentation as well as the disk formation, outflow generation and chemical processes during highmass star formation on spatial scales of individual cores. Methods. Using the IRAM Northern Extended Millimeter Array (NOEMA) in combination with the 30 m telescope, we have observed in the IRAM large program CORE the 1.37 mm continuum and spectral line emission at high angular resolution (?0.4??) for a sample of 20 well-known high-mass star-forming regions with distances below 5.5 kpc and luminosities larger than 104 L?. Results. We present the overall survey scope, the selected sample, the observational setup and the main goals of CORE. Scientifically, we concentrate on the mm continuum emission on scales on the order of 1000 AU. We detect strong mm continuum emission from all regions, mostly due to the emission from cold dust. The fragmentation properties of the sample are diverse. We see extremes where some regions are dominated by a single high-mass core whereas others fragment into as many as 20 cores. A minimum-spanning-tree analysis finds fragmentation at scales on the order of the thermal Jeans length or smaller suggesting that turbulent fragmentation is less important than thermal gravitational fragmentation. The diversity of highly fragmented versus singular regions can be explained by varying initial density structures and/or different initial magnetic field strengths. Conclusions. A large sample of high-mass star-forming regions at high spatial resolution allows us to study the fragmentation properties of young cluster-forming regions. The smallest observed separations between cores are found around the angular resolution limit which indicates that further fragmentation likely takes place on even smaller spatial scales. The CORE project with its numerous spectral line detections will address a diverse set of important physical and chemical questions in the field of high-mass star formation

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H