Direct Evidence that Bevacizumab, an Anti-VEGF Antibody, Up-regulates SDF1 , CXCR4, CXCL6, and Neuropilin 1 in Tumors from Patients with Rectal Cancer

Clinical studies converge on the observation that circulating cytokines are elevated in most cancer patients by anti-vascular endothelial growth factor (VEGF) therapy. However, the source of these molecules and their relevance in tumor escape remain unknown. We examined the gene expression profiles of cancer cells and tumor-associated macrophages in tumor biopsies before and 12 days after monotherapy with the anti-VEGF antibody bevacizumab in patients with rectal carcinoma. Bevacizumab up-regulated stromal cell-derived factor 1alpha (SDF1alpha), its receptor CXCR4, and CXCL6, and down-regulated PlGF, Ang1, and Ang2 in cancer cells. In addition, bevacizumab decreased Ang1 and induced neuropilin 1 (NRP1) expression in tumor-associated macrophages. Higher SDF1alpha plasma levels during bevacizumab treatment significantly associated with distant metastasis at three years. These data show that VEGF blockade up-regulates inflammatory pathways and NRP1, which should be evaluated as potential targets for improving anti-VEGF therapy

The Sulfur Microbial Diet Is Associated With Increased Risk of Early-Onset Colorectal Cancer Precursors

Background & Aims: Diet may contribute to the increasing incidence of colorectal cancer (CRC) before age 50 (early-onset CRC). Microbial metabolism of dietary sulfur produces hydrogen sulfide (H2S), a gastrointestinal carcinogen that cannot be easily measured at scale. As a result, evidence supporting its role in early neoplasia is lacking. Methods: We evaluated long-term adherence to the sulfur microbial diet, a dietary index defined a priori based on increased abundance of 43 bacterial species involved with sulfur metabolism, with risk of CRC precursors among 59,013 individuals who underwent lower endoscopy in the Nurses’ Health Study II (1991–2015), a prospective cohort study with dietary assessment every 4 years through validated food frequency questionnaires and an assessment of dietary intake during adolescence in 1998. The sulfur microbial diet was characterized by intake high in processed meats, foods previously linked to CRC development, and low in mixed vegetables and legumes. Multivariable logistic regression for clustered data was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: We documented 2911 cases of early-onset adenoma. After adjusting for established risk factors, higher sulfur microbial diet scores were associated with increased risk for early-onset adenomas (ORquartile [Q]4 vs Q1, 1.31; 95% CI, 1.10–1.56, Ptrend = .02), but not serrated lesions. Compared with the lowest, women in the highest quartile of sulfur microbial diet scores had significantly increased risk of early-onset adenomas with greater malignant potential (ORQ4 vs Q1, 1.65 for villous/tubulovillous histology; 95% CI, 1.12–2.43; Ptrend = .04). Similar trends for early-onset adenoma were observed based on diet consumed during adolescence. In contrast, no clear association for adenomas was identified after age 50. Conclusions: Our findings in a cohort of young women support a role for dietary interactions with gut sulfur-metabolizing bacteria in early-onset colorectal carcinogenesis, possibly beginning in adolescence. Includes Supplemental materials

Galaxy Zoo: CANDELS barred discs and bar fractions

The formation of bars in disc galaxies is a tracer of the dynamical maturity of the population. Previous studies have found that the incidence of bars in discs decreases from the local Universe to z ~ 1, and by z > 1 simulations predict that bar features in dynamically mature discs should be extremely rare. Here, we report the discovery of strong barred structures in massive disc galaxies at z ~ 1.5 in deep rest-frame optical images from the Cosmic Assembly Near-Infrared Deep Extragalactic Legacy Survey. From within a sample of 876 disc galaxies identified by visual classification in Galaxy Zoo, we identify 123 barred galaxies. Selecting a subsample within the same region of the evolving galaxy luminosity function (brighter than L*), we find that the bar fraction across the redshift range 0.5 ≤ z ≤ 2 (fbar = 10.7+6.3 -3.5 per cent after correcting for incompleteness) does not significantly evolve.We discuss the implications of this discovery in the context of existing simulations and our current understanding of the way disc galaxies have evolved over the last 11 billion yearsPeer reviewedFinal Accepted Versio

A gene-based SNP resource and linkage map for the copepod Tigriopus californicus

<p>Abstract</p> <p>Background</p> <p>As yet, few genomic resources have been developed in crustaceans. This lack is particularly evident in Copepoda, given the extraordinary numerical abundance, and taxonomic and ecological diversity of this group. <it>Tigriopus californicus </it>is ideally suited to serve as a genetic model copepod and has been the subject of extensive work in environmental stress and reproductive isolation. Accordingly, we set out to develop a broadly-useful panel of genetic markers and to construct a linkage map dense enough for quantitative trait locus detection in an interval mapping framework for <it>T. californicus--</it>a first for copepods.</p> <p>Results</p> <p>One hundred and ninety Single Nucleotide Polymorphisms (SNPs) were used to genotype our mapping population of 250 F₂larvae. We were able to construct a linkage map with an average intermarker distance of 1.8 cM, and a maximum intermarker distance of 10.3 cM. All markers were assembled into linkage groups, and the 12 linkage groups corresponded to the 12 known chromosomes of <it>T. californicus</it>. We estimate a total genome size of 401.0 cM, and a total coverage of 73.7%. Seventy five percent of the mapped markers were detected in 9 additional populations of <it>T. californicus</it>. Of available model arthropod genomes, we were able to show more colocalized pairs of homologues between <it>T. californicus </it>and the honeybee <it>Apis mellifera</it>, than expected by chance, suggesting preserved macrosynteny between Hymenoptera and Copepoda.</p> <p>Conclusions</p> <p>Our study provides an abundance of linked markers spanning all chromosomes. Many of these markers are also found in multiple populations of <it>T. californicus</it>, and in two other species in the genus. The genomic resource we have developed will enable mapping throughout the geographical range of this species and in closely related species. This linkage map will facilitate genome sequencing, mapping and assembly in an ecologically and taxonomically interesting group for which genomic resources are currently under development.</p

Fried food consumption, genetic risk, and body mass index: gene-diet interaction analysis in three US cohort studies

Objective: To examine the interactions between genetic predisposition and consumption of fried food in relation to body mass index (BMI) and obesity. Design: Prospective cohort study. Setting: Health professionals in the United States. Participants: 9623 women from the Nurses’ Health Study, 6379 men from the Health Professionals Follow-up Study, and a replication cohort of 21 421 women from the Women’s Genome Health Study. Main outcome measure Repeated measurement of BMI over follow-up. Results: There was an interaction between fried food consumption and a genetic risk score based on 32 BMI-associated variants on BMI in both the Nurses’ Health Study and Health Professionals Follow-up Study (P≤0.001 for interaction). Among participants in the highest third of the genetic risk score, the differences in BMI between individuals who consumed fried foods four or more times a week and those who consumed fried foods less than once a week amounted to 1.0 (SE 0.2) in women and 0.7 (SE 0.2) in men, whereas the corresponding differences were 0.5 (SE 0.2) and 0.4 (SE 0.2) in the lowest third of the genetic risk score. The gene-diet interaction was replicated in the Women’s Genome Health Study (P<0.001 for interaction). Viewed differently, the genetic association with adiposity was strengthened with higher consumption of fried foods. In the combined three cohorts, the differences in BMI per 10 risk alleles were 1.1 (SE 0.2), 1.6 (SE 0.3), and 2.2 (SE 0.6) for fried food consumption less than once, one to three times, and four or more times a week (P<0.001 for interaction); and the odds ratios (95% confidence intervals) for obesity per 10 risk alleles were 1.61 (1.40 to 1.87), 2.12 (1.73 to 2.59), and 2.72 (2.12 to 3.48) across the three categories of consumption (P=0.002 for interaction). In addition, the variants in or near genes highly expressed or known to act in the central nervous system showed significant interactions with fried food consumption, with the FTO (fat mass and obesity associated) variant showing the strongest result (P<0.001 for interaction). Conclusion: Our findings suggest that consumption of fried food could interact with genetic background in relation to obesity, highlighting the particular importance of reducing fried food consumption in individuals genetically predisposed to obesity

Detection of SARS‐CoV‐2 in respiratory samples from cats in the UK associated with human‐to‐cat transmission

Objectives: The aim of the study was to find evidence of SARS‐CoV‐2 infection in UK cats. Design: Tissue samples were tested for SARS‐CoV‐2 antigen using immunofluorescence and for viral RNA by in situ hybridisation. A set of 387 oropharyngeal swabs that had been submitted for routine respiratory pathogen testing was tested for SARS‐CoV‐2 RNA using reverse transcriptase quantitative PCR. Results: Lung tissue collected post‐mortem from cat 1 tested positive for both SARS‐CoV‐2 nucleocapsid antigen and RNA. SARS‐CoV‐2 RNA was detected in an oropharyngeal swab collected from cat 2 that presented with rhinitis and conjunctivitis. High throughput sequencing of the viral genome revealed five single nucleotide polymorphisms (SNPs) compared to the nearest UK human SARS‐CoV‐2 sequence, and this human virus contained eight SNPs compared to the original Wuhan‐Hu‐1 reference sequence. An analysis of the viral genome of cat 2 together with nine other feline‐derived SARS‐CoV‐2 sequences from around the world revealed no shared cat‐specific mutations. Conclusions: These findings indicate that human‐to‐cat transmission of SARS‐CoV‐2 occurred during the COVID‐19 pandemic in the UK, with the infected cats developing mild or severe respiratory disease. Given the ability of the new coronavirus to infect different species, it will be important to monitor for human‐to‐cat, cat‐to‐cat and cat‐to‐human transmission

MACiE: exploring the diversity of biochemical reactions

MACiE (which stands for Mechanism, Annotation and Classification in Enzymes) is a database of enzyme reaction mechanisms, and can be accessed from http://www.ebi.ac.uk/thornton-srv/databases/MACiE/. This article presents the release of Version 3 of MACiE, which not only extends the dataset to 335 entries, covering 182 of the EC sub-subclasses with a crystal structure available (∼90%), but also incorporates greater chemical and structural detail. This version of MACiE represents a shift in emphasis for new entries, from non-homologous representatives covering EC reaction space to enzymes with mechanisms of interest to our users and collaborators with a view to exploring the chemical diversity of life. We present new tools for exploring the data in MACiE and comparing entries as well as new analyses of the data and new searches, many of which can now be accessed via dedicated Perl scripts

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

BEBOP V. Homogeneous stellar analysis of potential circumbinary planet hosts

Planets orbiting binary systems are relatively unexplored compared to those around single stars. Detections of circumbinary planets and planetary systems offer a first detailed view into our understanding of circumbinary planet formation and dynamical evolution. The BEBOP (binaries escorted by orbiting planets) radial velocity survey plays a special role in this adventure as it focuses on eclipsing single-lined binaries with an FGK dwarf primary and M dwarf secondary allowing for the highest radial velocity precision using the HARPS and SOPHIE spectrographs. We obtained 4512 high-resolution spectra for the 179 targets in the BEBOP survey which we used to derive the stellar atmospheric parameters using both equivalent widths and spectral synthesis. We furthermore derive stellar masses, radii, and ages for all targets. With this work, we present the first homogeneous catalogue of precise stellar parameters for these eclipsing single-lined binaries

BEBOP V. Homogeneous stellar analysis of potential circumbinary planet hosts

Planets orbiting binary systems are relatively unexplored compared to those around single stars. Detections of circumbinary planets and planetary systems offer a first detailed view into our understanding of circumbinary planet formation and dynamical evolution. The BEBOP (binaries escorted by orbiting planets) radial velocity survey plays a special role in this adventure as it focuses on eclipsing single-lined binaries with an FGK dwarf primary and M dwarf secondary allowing for the highest radial velocity precision using the HARPS and SOPHIE spectrographs. We obtained 4512 high-resolution spectra for the 179 targets in the BEBOP survey which we used to derive the stellar atmospheric parameters using both equivalent widths and spectral synthesis. We furthermore derive stellar masses, radii, and ages for all targets. With this work, we present the first homogeneous catalogue of precise stellar parameters for these eclipsing single-lined binaries