The population genomics of archaeological transition in west Iberia: Investigation of ancient substructure using imputation and haplotype-based methods

We analyse new genomic data (0.05–2.95x) from 14 ancient individuals from Portugal distributed from the Middle Neolithic (4200–3500 BC) to the Middle Bronze Age (1740–1430 BC) and impute genomewide diploid genotypes in these together with published ancient Eurasians. While discontinuity is evident in the transition to agriculture across the region, sensitive haplotype-based analyses suggest a significant degree of local hunter-gatherer contribution to later Iberian Neolithic populations. A more subtle genetic influx is also apparent in the Bronze Age, detectable from analyses including haplotype sharing with both ancient and modern genomes, D-statistics and Y-chromosome lineages. However, the limited nature of this introgression contrasts with the major Steppe migration turnovers within third Millennium northern Europe and echoes the survival of non-Indo-European language in Iberia. Changes in genomic estimates of individual height across Europe are also associated with these major cultural transitions, and ancestral components continue to correlate with modern differences in stature

184 UPLIFT (ENGOT-ov67/GOG-3048) a pivotal cohort of upifitamab rilsodotin, a NaPi2b-directed ADC in platinum-resistant ovarian cancer

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Incidence of chemotherapy-induced amenorrhea associated with epirubicin, docetaxel and navelbine in younger breast cancer patients

<p>Abstract</p> <p>Background</p> <p>The rates of chemotherapy-induced amenorrhea (CIA) associated with docetaxel-based regimens reported by previous studies are discordant. For navelbine-based chemotherapies, rates of CIA have seldom been reported.</p> <p>Methods</p> <p>Of 170 premenopausal patients recruited between January 2003 and September 2008, 78 were treated with fluorouracil plus epirubicin and cyclophosphamide (FEC), 66 were treated with docetaxel plus epirubicin (TE), and 26 were treated with navelbine plus epirubicin (NE). Patient follow-up was carried up every 3-4 months during the first year, then every 9-12 months during subsequent years.</p> <p>Results</p> <p>In univariate analysis, the rates of CIA were 44.87% for the FEC regimen, 30.30% for the TE regimen and 23.08% for the NE regimen (<it>P </it>= 0.068). Significant differences in the rates of CIA were not found between the FEC and TE treatment groups (<it>P </it>> 0.05), but were found between the FEC and NE treatment groups (<it>P </it>< 0.05). Furthermore, no significant differences were found between the TE and NE regimens (<it>P </it>> 0.05). Tamoxifen use was a significant predictor for CIA (<it>P </it>= 0.001), and age was also a significant predictor (<it>P </it>< 0.001). In multivariate analysis, age (<it>P </it>< 0.001), the type of chemotherapy regimens (<it>P </it>= 0.009) and tamoxifen use (<it>P </it>= 0.003) were all significant predictors.</p> <p>Conclusions</p> <p>Age and administration of tamoxifen were found to be significant predictive factors of CIA, whereas docetaxel and navelbine based regimens were not associated with higher rates of CIA than epirubicin-based regimen.</p

A Tradeoff Drives the Evolution of Reduced Metal Resistance in Natural Populations of Yeast

Various types of genetic modification and selective forces have been implicated in the process of adaptation to novel or adverse environments. However, the underlying molecular mechanisms are not well understood in most natural populations. Here we report that a set of yeast strains collected from Evolution Canyon (EC), Israel, exhibit an extremely high tolerance to the heavy metal cadmium. We found that cadmium resistance is primarily caused by an enhanced function of a metal efflux pump, PCA1. Molecular analyses demonstrate that this enhancement can be largely attributed to mutations in the promoter sequence, while mutations in the coding region have a minor effect. Reconstruction experiments show that three single nucleotide substitutions in the PCA1 promoter quantitatively increase its activity and thus enhance the cells' cadmium resistance. Comparison among different yeast species shows that the critical nucleotides found in EC strains are conserved and functionally important for cadmium resistance in other species, suggesting that they represent an ancestral type. However, these nucleotides had diverged in most Saccharomyces cerevisiae populations, which gave cells growth advantages under conditions where cadmium is low or absent. Our results provide a rare example of a selective sweep in yeast populations driven by a tradeoff in metal resistance

From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways

The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut-brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies.GB Rogers, DJ Keating, RL Young, M-L Wong, J Licinio, and S Wesseling

Coupling microdroplet microreactors with mass spectrometry: reading the contents of single droplets online.

Fully integrated: Mass spectrometry has been integrated into a detection scheme for microdroplets that are created within microfluidic channels (see picture, scale bar 200 microm). This technique allows droplets to be identified based on the compounds they contain, and combines fluorescence screening with MS analysis. These experiments indicate how similar approaches can be applied to the ambitious goals of on-chip protein evolution and chemical synthesis