Astrochemistry - Complex organic matter in Titan's aerosols? Reply

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62938/1/nature05418.pd

Curiosity's Sample Analysis at Mars (SAM) Investigation: Overview of Results from the First 120 Sols on Mars

During the first 120 sols of Curiosity s landed mission on Mars (8/6/2012 to 12/7/2012) SAM sampled the atmosphere 9 times and an eolian bedform named Rocknest 4 times. The atmospheric experiments utilized SAM s quadrupole mass spectrometer (QMS) and tunable laser spectrometer (TLS) while the solid sample experiments also utilized the gas chromatograph (GC). Although a number of core experiments were pre-programmed and stored in EEProm, a high level SAM scripting language enabled the team to optimize experiments based on prior runs

Detection of Nitric Oxide by the Sample Analysis at Mars (SAM) Instrument Implications for the Presence of Nitrates

One of the main goals of the Mars Science Laboratory is to determine whether the planet ever had environmental conditions able to support microbial life. Nitrogen is a fundamental element for life, and is present in structural (e.g., proteins), catalytic (e.g., enzymes and ribozymes), energy transfer (e.g., ATP) and information storage (RNA and DNA) biomolecules. Planetary models suggest that molecular nitrogen was abundant in the early Martian atmosphere, but was rapidly lost to space by photochemistry, sputtering impact erosion, and oxidized and deposited to the surface as nitrate. Nitrates are a fundamental source for nitrogen to terrestrial microorganisms. Therefore, the detection of nitrates in soils and rocks is important to assess the habitability of a Martian environment. SAM is capable of detecting nitrates by their thermal decomposition into nitric oxide, NO. Here we analyze the release of NO from soils and rocks examined by the SAM instrument at Gale crater, and discuss its origin

Deciphering the complex interplay between pancreatic cancer, diabetes mellitus subtypes and obesity/BMI through causal inference and mediation analyses.

OBJECTIVES: To characterise the association between type 2 diabetes mellitus (T2DM) subtypes (new-onset T2DM (NODM) or long-standing T2DM (LSDM)) and pancreatic cancer (PC) risk, to explore the direction of causation through Mendelian randomisation (MR) analysis and to assess the mediation role of body mass index (BMI). DESIGN: Information about T2DM and related factors was collected from 2018 PC cases and 1540 controls from the PanGenEU (European Study into Digestive Illnesses and Genetics) study. A subset of PC cases and controls had glycated haemoglobin, C-peptide and genotype data. Multivariate logistic regression models were applied to derive ORs and 95% CIs. T2DM and PC-related single nucleotide polymorphism (SNP) were used as instrumental variables (IVs) in bidirectional MR analysis to test for two-way causal associations between PC, NODM and LSDM. Indirect and direct effects of the BMI-T2DM-PC association were further explored using mediation analysis. RESULTS: T2DM was associated with an increased PC risk when compared with non-T2DM (OR=2.50; 95% CI: 2.05 to 3.05), the risk being greater for NODM (OR=6.39; 95% CI: 4.18 to 9.78) and insulin users (OR=3.69; 95% CI: 2.80 to 4.86). The causal association between T2DM (57-SNP IV) and PC was not statistically significant (ORLSDM=1.08, 95% CI: 0.86 to 1.29, ORNODM=1.06, 95% CI: 0.95 to 1.17). In contrast, there was a causal association between PC (40-SNP IV) and NODM (OR=2.85; 95% CI: 2.04 to 3.98), although genetic pleiotropy was present (MR-Egger: p value=0.03). Potential mediating effects of BMI (125-SNPs as IV), particularly in terms of weight loss, were evidenced on the NODM-PC association (indirect effect for BMI in previous years=0.55). CONCLUSION: Findings of this study do not support a causal effect of LSDM on PC, but suggest that PC causes NODM. The interplay between obesity, PC and T2DM is complex

Changing outcomes following pelvic exenteration for locally advanced and recurrent rectal cancer

Background Pelvic exenteration for locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) is technically challenging but increasingly performed in specialist centres. The aim of this study was to compare outcomes of exenteration over time. Methods This was a multicentre retrospective study of patients who underwent exenteration for LARC and LRRC between 2004 and 2015. Surgical outcomes, including rate of bone resection, flap reconstruction, margin status and transfusion rates, were examined. Outcomes between higher- and lower-volume centres were also evaluated. Results Some 2472 patients underwent pelvic exenteration for LARC and LRRC across 26 institutions. For LARC, rates of bone resection or flap reconstruction increased from 2004 to 2015, from 3.5 to 12.8 per cent, and from 12.0 to 29.4 per cent respectively. Fewer units of intraoperative blood were transfused over this interval (median 4 to 2 units; P = 0.040). Subgroup analysis showed that bone resection and flap reconstruction rates increased in lower- and higher-volume centres. R0 resection rates significantly increased in low-volume centres but not in high-volume centres over time (low-volume: from 62.5 to 80.0 per cent, P = 0.001; high-volume: from 83.5 to 88.4 per cent, P = 0.660). For LRRC, no significant trends over time were observed for bone resection or flap reconstruction rates. The median number of units of intraoperative blood transfused decreased from 5 to 2.5 units (P < 0.001). R0 resection rates did not increase in either low-volume (from 51.7 to 60.4 per cent; P = 0.610) or higher-volume (from 48.6 to 65.5 per cent; P = 0.100) centres. No significant differences in length of hospital stay, 30-day complication, reintervention or mortality rates were observed over time. Conclusion Radical resection, bone resection and flap reconstruction rates were performed more frequently over time, while transfusion requirements decreased

Complex organic matter in Titan's atmospheric aerosols from in situ pyrolysis and analysis

Aerosols in Titan's atmosphere play an important role in determining its thermal structure(1-3). They also serve as sinks for organic vapours(4) and can act as condensation nuclei for the formation of clouds(5,6), where the condensation efficiency will depend on the chemical composition of the aerosols(5,7). So far, however, no direct information has been available on the chemical composition of these particles. Here we report an in situ chemical analysis of Titan's aerosols by pyrolysis at 600 degrees C. Ammonia (NH3) and hydrogen cyanide (HCN) have been identified as the main pyrolysis products. This clearly shows that the aerosol particles include a solid organic refractory core. NH3 and HCN are gaseous chemical fingerprints of the complex organics that constitute this core, and their presence demonstrates that carbon and nitrogen are in the aerosols.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62786/1/nature04349.pd

Comparative structural and functional analysis of Bunyavirus and Arenavirus cap-snatching Endonucleases

Segmented negative strand RNA viruses of the arena-, bunya- and orthomyxovirus families uniquely carry out viral mRNA transcription by the cap-snatching mechanism. This involves cleavage of host mRNAs close to their capped 5′ end by an endonuclease (EN) domain located in the N-terminal region of the viral polymerase. We present the structure of the cap-snatching EN of Hantaan virus, a bunyavirus belonging to hantavirus genus. Hantaan EN has an active site configuration, including a metal co-ordinating histidine, and nuclease activity similar to the previously reported La Crosse virus and Influenza virus ENs (orthobunyavirus and orthomyxovirus respectively), but is more active in cleaving a double stranded RNA substrate. In contrast, Lassa arenavirus EN has only acidic metal co-ordinating residues. We present three high resolution structures of Lassa virus EN with different bound ion configurations and show in comparative biophysical and biochemical experiments with Hantaan, La Crosse and influenza ENs that the isolated Lassa EN is essentially inactive. The results are discussed in the light of EN activation mechanisms revealed by recent structures of full-length influenza virus polymerase

Contemporary Management of Locally Advanced and Recurrent Rectal Cancer: Views from the PelvEx Collaborative

Pelvic exenteration is a complex operation performed for locally advanced and recurrent pelvic cancers. The goal of surgery is to achieve clear margins, therefore identifying adjacent or involved organs, bone, muscle, nerves and/or vascular structures that may need resection. While these extensive resections are potentially curative, they can be associated with substantial morbidity. Recently, there has been a move to centralize care to specialized units, as this facilitates better multi-disciplinary care input. Advancements in pelvic oncology and surgical innovation have redefined the boundaries of pelvic exenterative surgery. Combined with improved neoadjuvant therapies, advances in diagnostics, and better reconstructive techniques have provided quicker recovery and better quality of life outcomes, with improved survival This article provides highlights of the current management of advanced pelvic cancers in terms of surgical strategy and potential future developments

Tumour macrophages as potential targets of bisphosphonates

Tumour cells communicate with the cells of their microenvironment via a series of molecular and cellular interactions to aid their progression to a malignant state and ultimately their metastatic spread. Of the cells in the microenvironment with a key role in cancer development, tumour associated macrophages (TAMs) are among the most notable. Tumour cells release a range of chemokines, cytokines and growth factors to attract macrophages, and these in turn release numerous factors (e.g. VEGF, MMP-9 and EGF) that are implicated in invasion-promoting processes such as tumour cell growth, flicking of the angiogenic switch and immunosuppression. TAM density has been shown to correlate with poor prognosis in breast cancer, suggesting that these cells may represent a potential therapeutic target. However, there are currently no agents that specifically target TAM's available for clinical use

Sex change and effective population size : implications for population genetic studies in marine fish

Large variance in reproductive success is the primary factor that reduces effective population size (Ne) in natural populations. In sequentially hermaphroditic (‘sex-changing’) fish, the sex ratio is typically skewed and biased toward the ‘first’ sex, while reproductive success increases considerably after sex change. Therefore, sex-changing fish populations are theoretically expected to have lower Ne than gonochorists (separate sexes), assuming all other parameters are essentially equal. In this study, we estimate Ne from genetic data collected from two ecologically similar species living along the eastern coast of South Africa: one gonochoristic, the ‘santer’ sea bream Cheimerius nufar, and one protogynous (female-first) sex-changer, the ‘slinger’ sea bream Chrysoblephus puniceus. For both species, no evidence of geneticstructuring, nor significant variation in genetic diversity, were found in the study area. Estimates of contemporary Ne were significantly lower in the protogynous species, but the same pattern was not apparent over historical timescales. Overall, our results show that sequential hermaphroditism may affect Ne differently over varying time frames, and that demographic signatures inferred from genetic markers with different inheritance modes also need to be interpreted cautiously, in relation to sex-changing lifehistories