Mitochondrial DNA signature for range-wide populations of Bicyclus anynana suggests a rapid expansion from recent refugia

This study investigates the genetic diversity, population structure and demographic history of the afrotropical butterfly Bicyclus anynana using mitochondrial DNA (mtDNA). Samples from six wild populations covering most of the species range from Uganda to South Africa were compared for the cytochrome c oxidase subunit gene (COI). Molecular diversity indices show overall high mtDNA diversity for the populations, but low nucleotide divergence between haplotypes. Our results indicate relatively little geographic population structure among the southern populations, especially given the extensive distributional range and an expectation of limited gene flow between populations. We implemented neutrality tests to assess signatures of recent historical demographic events. Tajima's D test and Fu's FS test both suggested recent population growth for the populations. The results were only significant for the southernmost populations when applying Tajima's D, but Fu's FS indicated significant deviations from neutrality for all populations except the one closest to the equator. Based on our own findings and those from pollen and vegetation studies, we hypothesize that the species range of B. anynana was reduced to equatorial refugia during the last glacial period, and that the species expanded southwards during the past 10.000 years. These results provide crucial background information for studies of phenotypic and molecular adaptation in wild populations of B. anynan

The transcriptome in transition: global gene expression profiles of young adult fruit flies depend more strongly on developmental than adult diet

Developmental diet is known to exert long-term effects on adult phenotypes in many animal species as well as disease risk in humans, purportedly mediated through long-term changes in gene expression. However, there are few studies linking developmental diet to adult gene expression. Here, we use a full-factorial design to address how three different larval and adult diets interact to affect gene expression in 1-day-old adult fruit flies (Drosophila melanogaster) of both sexes. We found that the largest contributor to transcriptional variation in young adult flies is larval, and not adult diet, particularly in females. We further characterized gene expression variation by applying weighted gene correlation network analysis (WGCNA) to identify modules of co-expressed genes. In adult female flies, the caloric content of the larval diet associated with two strongly negatively correlated modules, one of which was highly enriched for reproduction-related processes. This suggests that gene expression in young adult female flies is in large part related to investment into reproduction-related processes, and that the level of expression is affected by dietary conditions during development. In males, most modules had expression patterns independent of developmental or adult diet. However, the modules that did correlate with larval and/or adult dietary regimes related primarily to nutrient sensing and metabolic functions, and contained genes highly expressed in the gut and fat body. The gut and fat body are among the most important nutrient sensing tissues, and are also the only tissues known to avoid histolysis during pupation. This suggests that correlations between larval diet and gene expression in male flies may be mediated by the carry-over of these tissues into young adulthood. Our results show that developmental diet can have profound effects on gene expression in early life and warrant future research into how they correlate with actual fitness related traits in early adulthood.Molecular Epidemiolog

Cosmological distance indicators

We review three distance measurement techniques beyond the local universe: (1) gravitational lens time delays, (2) baryon acoustic oscillation (BAO), and (3) HI intensity mapping. We describe the principles and theory behind each method, the ingredients needed for measuring such distances, the current observational results, and future prospects. Time delays from strongly lensed quasars currently provide constraints on $H_0$ with < 4% uncertainty, and with 1% within reach from ongoing surveys and efforts. Recent exciting discoveries of strongly lensed supernovae hold great promise for time-delay cosmography. BAO features have been detected in redshift surveys up to z <~ 0.8 with galaxies and z ~ 2 with Ly-$\alpha$ forest, providing precise distance measurements and $H_0$ with < 2% uncertainty in flat $\Lambda$CDM. Future BAO surveys will probe the distance scale with percent-level precision. HI intensity mapping has great potential to map BAO distances at z ~ 0.8 and beyond with precisions of a few percent. The next years ahead will be exciting as various cosmological probes reach 1% uncertainty in determining $H_0$, to assess the current tension in $H_0$ measurements that could indicate new physics.Comment: Review article accepted for publication in Space Science Reviews (Springer), 45 pages, 10 figures. Chapter of a special collection resulting from the May 2016 ISSI-BJ workshop on Astronomical Distance Determination in the Space Ag

Implementation of paediatric precision oncology into clinical practice: The Individualized Therapies for Children with cancer program ‘iTHER’

iTHER is a Dutch prospective national precision oncology program aiming to define tumour molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory paediatric tumours. Between April 2017 and April 2021, 302 samples from 253 patients were included. Comprehensive molecular profiling including low-coverage whole genome sequencing (lcWGS), whole exome sequencing (WES), RNA sequencing (RNA-seq), Affymetrix, and/or 850k methylation profiling was successfully performed for 226 samples with at least 20% tumour content. Germline pathogenic variants were identified in 16% of patients (35/219), of which 22 variants were judged causative for a cancer predisposition syndrome. At least one somatic alteration was detected in 204 (90.3%), and 185 (81.9%) were considered druggable, with clinical priority very high (6.1%), high (21.3%), moderate (26.0%), intermediate (36.1%), and borderline (10.5%) priority. iTHER led to revision or refinement of diagnosis in 8 patients (3.5%). Temporal heterogeneity was observed in paired samples of 15 patients, indicating the value of sequential analyses. Of 137 patients with follow-up beyond twelve months, 21 molecularly matched treatments were applied in 19 patients (13.9%), with clinical benefit in few. Most relevant barriers to not applying targeted therapies included poor performance status, as well as limited access to drugs within clinical trial. iTHER demonstrates the feasibility of comprehensive molecular profiling across all ages, tumour types and stages in paediatric cancers, informing of diagnostic, prognostic, and targetable alterations as well as reportable germline variants. Therefore, WES and RNA-seq is nowadays standard clinical care at the Princess Máxima Center for all children with cancer, including patients at primary diagnosis. Improved access to innovative treatments within biology-driven combination trials is required to ultimately improve survival

Implementation of paediatric precision oncology into clinical practice: The Individualized Therapies for Children with cancer program ‘iTHER’

iTHER is a Dutch prospective national precision oncology program aiming to define tumour molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory paediatric tumours. Between April 2017 and April 2021, 302 samples from 253 patients were included. Comprehensive molecular profiling including low-coverage whole genome sequencing (lcWGS), whole exome sequencing (WES), RNA sequencing (RNA-seq), Affymetrix, and/or 850k methylation profiling was successfully performed for 226 samples with at least 20% tumour content. Germline pathogenic variants were identified in 16% of patients (35/219), of which 22 variants were judged causative for a cancer predisposition syndrome. At least one somatic alteration was detected in 204 (90.3%), and 185 (81.9%) were considered druggable, with clinical priority very high (6.1%), high (21.3%), moderate (26.0%), intermediate (36.1%), and borderline (10.5%) priority. iTHER led to revision or refinement of diagnosis in 8 patients (3.5%). Temporal heterogeneity was observed in paired samples of 15 patients, indicating the value of sequential analyses. Of 137 patients with follow-up beyond twelve months, 21 molecularly matched treatments were applied in 19 patients (13.9%), with clinical benefit in few. Most relevant barriers to not applying targeted therapies included poor performance status, as well as limited access to drugs within clinical trial. iTHER demonstrates the feasibility of comprehensive molecular profiling across all ages, tumour types and stages in paediatric cancers, informing of diagnostic, prognostic, and targetable alterations as well as reportable germline variants. Therefore, WES and RNA-seq is nowadays standard clinical care at the Princess Máxima Center for all children with cancer, including patients at primary diagnosis. Improved access to innovative treatments within biology-driven combination trials is required to ultimately improve survival