Subtle effects of environmental stress observed in the early life stages of the Common frog, Rana temporaria

Worldwide amphibian populations are declining due to habitat loss, disease and pollution. Vulnerability to environmental contaminants such as pesticides will be dependent on the species, the sensitivity of the ontogenic life stage and hence the timing of exposure and the exposure pathway. Herein we investigated the biochemical tissue ‘fingerprint’ in spawn and early-stage tadpoles of the Common frog, Rana temporaria, using attenuated total reflection- Fourier-transform infrared (ATR-FTIR) spectroscopy with the objective of observing differences in the biochemical constituents of the respective amphibian tissues due to varying water quality in urban and agricultural ponds. Our results demonstrate that levels of stress (marked by biochemical constituents such as glycogen that are involved in compensatory metabolic mechanisms) can be observed in tadpoles present in the pond most impacted by pollution (nutrients and pesticides), but large annual variability masked any inter-site differences in the frog spawn. ATR-FTIR spectroscopy is capable of detecting differences in tadpoles that are present in selected ponds with different levels of environmental perturbation and thus serves as a rapid and cost effective tool in assessing stress-related effects of pollution in a vulnerable class of organism

ATR-FTIR spectroscopy non-destructively detects damage-induced sour rot infection in whole tomato fruit

Main conclusion ATR-FTIR spectroscopy with subsequent multivariate analysis non-destructively identifies plant–pathogen interactions during disease progression, both directly and indirectly, through alterations in the spectral fingerprint. Plant–environment interactions are essential to understanding crop biology, optimizing crop use, and minimizing loss to ensure food security. Damage-induced pathogen infection of delicate fruit crops such as tomato (Solanum lycopersicum) are therefore important processes related to crop biology and modern horticulture. Fruit epidermis as a first barrier at the plant–environment interface, is specifically involved in environmental interactions and often shows substantial structural and functional changes in response to unfavourable conditions. Methods available to investigate such systems in their native form, however, are limited by often required and destructive sample preparation, or scarce amounts of molecular level information. To explore biochemical changes and evaluate diagnostic potential for damage-induced pathogen infection of cherry tomato (cv. Piccolo) both directly and indirectly, mid-infrared (MIR) spectroscopy was applied in combination with exploratory multivariate analysis. ATR-FTIR fingerprint spectra (1800–900 cm−1) of healthy, damaged or sour rot-infected tomato fruit were acquired and distinguished using principal component analysis and linear discriminant analysis (PCA–LDA). Main biochemical constituents of healthy tomato fruit epidermis are characterized while multivariate analysis discriminated subtle biochemical changes distinguishing healthy tomato from damaged, early or late sour rot-infected tomato indirectly based solely on changes in the fruit epidermis. Sour rot causing agent Geotrichum candidum was detected directly in vivo and characterized based on spectral features distinct from tomato fruit. Diagnostic potential for indirect pathogen detection based on tomato fruit skin was evaluated using the linear discriminant classifier (PCA–LDC). Exploratory and diagnostic analysis of ATR-FTIR spectra offers biological insights and detection potential for intact plant–pathogen systems as they are found in horticultural industries

Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort

Background: Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. Methods: In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MB WNT ), SHH (MB SHH ), group 3 (MB Group3 ), and group 4 (MB Group4 ). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. Findings: We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MB SHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MB SHH subgroup). Patients with germline APC mutations developed MB WNT and accounted for most (five [71%] of seven) cases of MB WNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MB SHH . Germline TP53 mutations presented only in childhood patients in the MB SHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MB SHH , MB Group3 , and MB Group4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 40–69) and 5-year overall survival was 65% (95% CI 52–81); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes. Interpretation: Genetic counselling and testing should be used as a standard-of-care procedure in patients with MB WNT and MB SHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics. Funding: German Cancer Aid; German Federal Ministry of Education and Research; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); European Research Council; National Institutes of Health; Canadian Institutes for Health Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer Research; Sontag Foundation; Musicians Against Childhood Cancer; BC Cancer Foundation; Swedish Council for Health, Working Life and Welfare; Swedish Research Council; Swedish Cancer Society; the Swedish Radiation Protection Authority; Danish Strategic Research Council; Swiss Federal Office of Public Health; Swiss Research Foundation on Mobile Communication; Masaryk University; Ministry of Health of the Czech Republic; Research Council of Norway; Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group of Ontario; The Family of Kathleen Lorette and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents Association; Cure Search Foundation; Pediatric Brain Tumor Foundation; Brainchild; and the Government of Ontario