Environmental chemicals impact dog semen quality in vitro and may be associated with a temporal decline in sperm motility and increased cryptorchidism

Adverse temporal trends in human semen quality and cryptorchidism in infants have been associated with exposure to environmental chemicals (ECs) during development. Here we report that a population of breeding dogs exhibit a 26 year (1988–2014) decline in sperm quality and a concurrent increased incidence of cryptorchidism in male offspring (1995–2014). A decline in the number of males born relative to the number of females was also observed. ECs, including diethylhexyl phthalate (DEHP) and polychlorinated biphenyl 153 (PCB153), were detected in adult dog testes and commercial dog foods at concentrations reported to perturb reproductive function in other species. Testicular concentrations of DEHP and PCB153 perturbed sperm viability, motility and DNA integrity in vitro but did not affect LH stimulated testosterone secretion from adult testis explants. The direct effects of chemicals on sperm may therefore contribute to the decline in canine semen quality that parallels that reported in the human

Company for the Ultra-high Density, Ultra-short Period Sub-Earth GJ 367 b: Discovery of Two Additional Low-mass Planets at 11.5 and 34 Days

GJ 367 is a bright (V ≈ 10.2) M1 V star that has been recently found to host a transiting ultra-short period sub-Earth on a 7.7 hr orbit. With the aim of improving the planetary mass and radius and unveiling the inner architecture of the system, we performed an intensive radial velocity follow-up campaign with the HARPS spectrograph—collecting 371 high-precision measurements over a baseline of nearly 3 yr—and combined our Doppler measurements with new TESS observations from sectors 35 and 36. We found that GJ 367 b has a mass of M b = 0.633 ± 0.050 M ⊕ and a radius of R b = 0.699 ± 0.024 R ⊕, corresponding to precisions of 8% and 3.4%, respectively. This implies a planetary bulk density of ρ b = 10.2 ± 1.3 g cm−3, i.e., 85% higher than Earth’s density. We revealed the presence of two additional non-transiting low-mass companions with orbital periods of ∼11.5 and 34 days and minimum masses of M c sin i c = 4.13 ± 0.36 M ⊕ and M d sin i d = 6.03 ± 0.49 M ⊕, respectively, which lie close to the 3:1 mean motion commensurability. GJ 367 b joins the small class of high-density planets, namely the class of super-Mercuries, being the densest ultra-short period small planet known to date. Thanks to our precise mass and radius estimates, we explored the potential internal composition and structure of GJ 367 b, and found that it is expected to have an iron core with a mass fraction of 0.91 − 0.23 + 0.07 . How this iron core is formed and how such a high density is reached is still not clear, and we discuss the possible pathways of formation of such a small ultra-dense planet

A novel, integrated in vitro carcinogenicity test to identify genotoxic and non-genotoxic carcinogens using human lymphoblastoid cells

Human exposure to carcinogens occurs via a plethora of environmental sources, with 70–90% of cancers caused by extrinsic factors. Aberrant phenotypes induced by such carcinogenic agents may provide universal biomarkers for cancer causation. Both current in vitro genotoxicity tests and the animal-testing paradigm in human cancer risk assessment fail to accurately represent and predict whether a chemical causes human carcinogenesis. The study aimed to establish whether the integrated analysis of multiple cellular endpoints related to the Hallmarks of Cancer could advance in vitro carcinogenicity assessment. Human lymphoblastoid cells (TK6, MCL-5) were treated for either 4 or 23 h with 8 known in vivo carcinogens, with doses up to 50% Relative Population Doubling (maximum 66.6 mM). The adverse effects of carcinogens on wide-ranging aspects of cellular health were quantified using several approaches; these included chromosome damage, cell signalling, cell morphology, cell-cycle dynamics and bioenergetic perturbations. Cell morphology and gene expression alterations proved particularly sensitive for environmental carcinogen identification. Composite scores for the carcinogens’ adverse effects revealed that this approach could identify both DNA-reactive and non-DNA reactive carcinogens in vitro. The richer datasets generated proved that the holistic evaluation of integrated phenotypic alterations is valuable for effective in vitro risk assessment, while also supporting animal test replacement. Crucially, the study offers valuable insights into the mechanisms of human carcinogenesis resulting from exposure to chemicals that humans are likely to encounter in their environment. Such an understanding of cancer induction via environmental agents is essential for cancer prevention

TOI-1130: A photodynamical analysis of a hot Jupiter in resonance with an inner low-mass planet

The TOI-1130 is a known planetary system around a K-dwarf consisting of a gas giant planet, TOI-1130 c on an 8.4-day orbit that is accompanied by an inner Neptune-sized planet, TOI-1130 b, with an orbital period of 4.1 days. We collected precise radial velocity (RV) measurements of TOI-1130 with the HARPS and PFS spectrographs as part of our ongoing RV follow-up program. We performed a photodynamical modeling of the HARPS and PFS RVs, along with transit photometry from the Transiting Exoplanet Survey Satellite (TESS) and the TESS Follow-up Observing Program (TFOP). We determined the planet masses and radii of TOI-1130 b and TOI-1130 c to be Mb = 19.28 ± 0.97M⊕ and Rb = 3.56 ± 0.13 R⊕, and Mc = 325.59 ± 5.59M⊕ and Rc = 13.32-1.41+1.55 R⊕, respectively. We have spectroscopically confirmed the existence of TOI-1130 b, which had previously only been validated. We find that the two planets have orbits with small eccentricities in a 2:1 resonant configuration. This is the first known system with a hot Jupiter and an inner lower mass planet locked in a mean-motion resonance. TOI-1130 belongs to the small, yet growing population of hot Jupiters with an inner low-mass planet that poses a challenge to the pathway scenario for hot Jupiter formation. We also detected a linear RV trend that is possibly due to the presence of an outer massive companion

Complex Interplay of Evolutionary Forces in the ladybird Homeobox Genes of Drosophila melanogaster

Tandemly arranged paralogous genes lbe and lbl are members of the Drosophila NK homeobox family. We analyzed population samples of Drosophila melanogaster from Africa, Europe, North and South America, and single strains of D. sechellia, D. simulans, and D. yakuba within two linked regions encompassing partial sequences of lbe and lbl. The evolution of lbe and lbl is highly constrained due to their important regulatory functions. Despite this, a variety of forces have shaped the patterns of variation in lb genes: recombination, intragenic gene conversion and natural selection strongly influence background variation created by linkage disequilibrium and dimorphic haplotype structure. The two genes exhibited similar levels of nucleotide diversity and positive selection was detected in the noncoding regions of both genes. However, synonymous variability was significantly higher for lbe: no nonsynonymous changes were observed in this gene. We argue that balancing selection impacts some synonymous sites of the lbe gene. Stability of mRNA secondary structure was significantly different between the lbe (but not lbl) haplotype groups and may represent a driving force of balancing selection in epistatically interacting synonymous sites. Balancing selection on synonymous sites may be the first, or one of a few such observations, in Drosophila. In contrast, recurrent positive selection on lbl at the protein level influenced evolution at three codon sites. Transcription factor binding-site profiles were different for lbe and lbl, suggesting that their developmental functions are not redundant. Combined with our previous results on nucleotide variation in esterase and other homeobox genes, these results suggest that interplay of balancing and directional selection may be a general feature of molecular evolution in Drosophila and other eukaryote genomes

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700