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Background: Liquid biopsy (LB) is a non-invasive tool to evaluate the heterogeneity of tumors. Since RAS mutations (RAS-mut) play a major role in resistance to antiepidermal growth factor receptor inhibitors (EGFR) monoclonal antibodies (Mabs), serial monitoring of RAS-mut with LB may be useful to guide treatment. The main aim of this study was to evaluate the prognostic value of the loss of RAS-mut (NeoRAS-wt) in LB, during the treatment of metastatic colorectal cancer (mCRC)., Methods: A retrospective study was conducted on patients with mCRC between January 2018 and December 2021. RAS-mut were examined in tissue biopsy, at mCRC diagnosis, and with LB, during treatment., Results: Thirty-nine patients with RAS-mut mCRC were studied. LB was performed after a median of 3 lines (0-7) of systemic treatment including anti-vascular endothelial growth factor (anti-VEGF) Mabs. NeoRAS-wt was detected in 13 patients (33.3%); 9 (69.2%) of them received further treatment with anti-EGFR Mabs with a disease control rate of 44.4%. Median overall survival (OS), from the date of LB testing, was 20 months in the NeoRAS-wt group and 9 months in the persistent RAS-mut group (log-rank 2.985; P = .08), with a 12-month OS of 84.6% and 57.7%, respectively. NeoRAS-wt was identified as a predictor of survival (HR = 0.29; P = .007), with an 11-month improvement in median OS and a 71% decrease in risk of death, in heavily pretreated patients., Conclusions: In conclusion, monitoring clonal evolution in mCRC by LB may provide an additional treatment line for patients with NeoRAS-wt in advanced disease., (© The Author(s) 2023. Published by Oxford University Press.)

Background and Aims: Golimumab has an established exposure-response relationship in patients with ulcerative colitis [UC]. However, the association of serum golimumab trough levels [TL] with objective markers of disease activity, such as endoscopic and histological activity scores and concentrations of biomarkers, remains less understood. This report describes the relationship of serum golimumab TL at the end of the induction period [Week 6] with clinical, endoscopic, histological, and biomarker parameters., Methods: This was an open-label, uncontrolled, prospective and interventional study. Moderate to severely active UC patients naïve to biologic therapy were treated with golimumab. Serum golimumab TL and faecal calprotectin levels were measured at baseline [Week 0 of induction] and Week 6., Results: A total of 34 patients completed the induction phase [Week 6] and were included in this analysis. Overall, 47.1% and 14.7% of patients achieved clinical response and remission with significantly higher serum golimumab TL in patients with early response or remission [3.7 μg/mL vs 1.3 μg/mL, p = 0.0013; and 3.1 μg/mL vs 1.7 μg/mL, p = 0.0164, respectively]. In addition, golimumab TL were significantly higher in patients achieving histological remission [4.2 μg/mL vs 1.7 μg/mL, p = 0.0049]. Week 6 golimumab TL were inversely correlated with the total Mayo score [rs = -0.546; p = 0.0008], the Mayo endoscopic subscore [rs = -0.381; p = 0.0262], the Geboes histological activity score [rs = -0.464; p = 0.0057], and faecal calprotectin levels [rs = -0.497; p = 0.0044]., Conclusions: A higher early exposure to golimumab is associated with a better objective response in active UC patients and appears to drive the outcome at Week 6., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The Austronesian dispersal across the Indonesian Ocean to Madagascar and the Comoros has been well documented, but in an unexplained anomaly, few to no traces have been found of the Austronesian expansion in East Africa or the Arabian Peninsula. To revisit this peculiarity, we surveyed the Western Indian Ocean rim populations to identify potential Austronesian genetic ancestry. We generated full mitochondrial DNA genomes and genome-wide genotyping data for these individuals and compared them with the Banjar, the Indonesian source population of the westward Austronesian dispersal. We find strong support for Asian genetic contributions to maternal lineages and autosomal variation in modern day Somalia and Yemen. Surprisingly, this input reveals two apparently different geographic origins and timings of admixture for the Austronesian contact; one at a very early phase (likely associated with the early Austronesian dispersals), and a later movement dating to the end of nineteenth century. These Austronesian gene flows come, respectively, from Madagascar and directly from an unidentified location in Island Southeast Asia. This result reveals a far more complex dynamic of Austronesian dispersals through the Western Indian Ocean than has previously been understood and suggests that Austronesian movements within the Indian Ocean may have been part of a lengthy process, probably continuing well into the modern era., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Genome-wide studies of African populations have the potential to reveal powerful insights into the evolution of our species, as these diverse populations have been exposed to intense selective pressures imposed by infectious diseases, diet, and environmental factors. Within Africa, the Sahel Belt extensively overlaps the geographical center of several endemic infections such as malaria, trypanosomiasis, meningitis, and hemorrhagic fevers. We screened 2.5 million single nucleotide polymorphisms in 161 individuals from 13 Sahelian populations, which together with published data cover Western, Central, and Eastern Sahel, and include both nomadic and sedentary groups. We confirmed the role of this Belt as a main corridor for human migrations across the continent. Strong admixture was observed in both Central and Eastern Sahelian populations, with North Africans and Near Eastern/Arabians, respectively, but it was inexistent in Western Sahelian populations. Genome-wide local ancestry inference in admixed Sahelian populations revealed several candidate regions that were significantly enriched for non-autochthonous haplotypes, and many showed to be under positive selection. The DARC gene region in Arabs and Nubians was enriched for African ancestry, whereas the RAB3GAP1/LCT/MCM6 region in Oromo, the TAS2R gene family in Fulani, and the ALMS1/NAT8 in Turkana and Samburu were enriched for non-African ancestry. Signals of positive selection varied in terms of geographic amplitude. Some genomic regions were selected across the Belt, the most striking example being the malaria-related DARC gene. Others were Western-specific (oxytocin, calcium, and heart pathways), Eastern-specific (lipid pathways), or even population-restricted (TAS2R genes in Fulani, which may reflect sexual selection)., (© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

A polymorphic inversion that lies on chromosome 17q21 comprises two major haplotype families (H1 and H2) that not only differ in orientation but also in copy-number. Although the processes driving the spread of the inversion-associated lineage (H2) in humans remain unclear, a selective advantage has been proposed for one of its subtypes. Here, we genotyped a large panel of individuals from previously overlooked populations using a custom array with a unique panel of H2-specific single nucleotide polymorphisms and found a patchy distribution of H2 haplotypes in Africa, with North Africans displaying a higher frequency of inverted subtypes, when compared with Sub-Saharan groups. Interestingly, North African H2s were found to be closer to "non-African" chromosomes further supporting that these populations may have diverged more recently from groups outside Africa. Our results uncovered higher diversity within the H2 family than previously described, weakening the hypothesis of a strong selective sweep on all inverted chromosomes and suggesting a rather complex evolutionary history at this locus., (© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

The quest for a universal and efficient method of identifying species has been a longstanding challenge in biology. Here, we show that accurate identification of species in all domains of life can be accomplished by multiplex analysis of variable-length sequences containing multiple insertion/deletion variants. The new method, called SPInDel, is able to discriminate 93.3% of eukaryotic species from 18 taxonomic groups. We also demonstrate that the identification of prokaryotic and viral species with numeric profiles of fragment lengths is generally straightforward. A computational platform is presented to facilitate the planning of projects and includes a large data set with nearly 1800 numeric profiles for species in all domains of life (1556 for eukaryotes, 105 for prokaryotes and 130 for viruses). Finally, a SPInDel profiling kit for discrimination of 10 mammalian species was successfully validated on highly processed food products with species mixtures and proved to be easily adaptable to multiple screening procedures routinely used in molecular biology laboratories. These results suggest that SPInDel is a reliable and cost-effective method for broad-spectrum species identification that is appropriate for use in suboptimal samples and is amenable to different high-throughput genotyping platforms without the need for DNA sequencing.

The first complete mitochondrial DNA (mtDNA) sequences (approximately 16,569 bp) in 20 patients with asthenozoospermia and a comparison with 23 new complete mtDNA sequences in teratoasthenozoospermic individuals, confirmed no sharing of specific polymorphisms or specific mitochondrial lineages between these individuals. This is strong evidence against the accepted claim of a major role played by mtDNA in male fertility, once supported by haplogroup association studies based on the screening of hypervariable region I. The hypothesis of maternally driven selection acting in male reproductive success must thus be treated with caution.

Highly adaptable and versatile populations of domestic sheep, the result of millennia of intense husbandry, are found in almost every corner of the world. Here we describe a genetic survey of sheep from the western fringe of its European distribution. We studied the mitochondrial DNA control region sequences from 161 individuals belonging to 7 Portuguese sheep breeds. Our study revealed a high level of genetic diversity, with an average breed haplotype diversity of 0.983, substantially above that observed in central European breeds, as well as the presence of maternal lineages until now only found in the Middle East and Asia. A broad north-south pattern describes the most important trend in the Portuguese sheep population with a southern population clearly distinct from most other breeds. A recurrent influx of new genetic diversity, probably via the Mediterranean Sea, may explain these patterns and appears to corroborate the importance of this maritime route in the history of both mankind and livestock. Zooarchaeological studies of sheep bones from southern Portugal indicate a marked size increase during the Moslem period that may reflect an improvement of this animal--perhaps part of the well known "Arab agricultural revolution" in Andalusia. This could have been a time when the gene pool of Iberian sheep was substantially enriched and may help to explain the history of modern sheep breeds in this peninsula.