15q11.2 microdeletion and FMR1 premutation in a family with intellectual disabilities and autism

Genomic rearrangements of chromosome 15q11–q13 are responsible for diverse phenotypes including intellectual disabilities and autism. 15q11.2 deletion, implicating common PWS/AS breakpoints BP1–BP2, has been described in patients with delayed motor and speech development and behavioural problems. Here we report the clinical and molecular characterisation of a maternally inherited BP1–BP2 deletion in two siblings with intellectual, motor and speech delay, autistic syndrome disorder and several dysmorphic features. One of the patients was also a carrier of an FMR1 allele in the low premutation range. The four genes within the deletion were under-expressed in all deletion carriers but FMR1 mRNA levels remained normal. Our results suggest that BP1-BP2 deletion could be considered as a risk factor for neuropsychological phenotypes and that it presents with variable clinical expressivity.     

Kappa agonist CovX-Bodies

Small peptidic kappa agonists were covalently linked to the reactive lysine of the CovX antibody to create compounds having potent activity at the kappa receptor with greatly extended half-life when compared to the parent peptide as exemplified by compound 20.     

Synthesis and cytotoxic activity of 4-N-carboxybutyl-5-fluorocytosyl-Arg-Gln-Trp-Arg-Arg-Trp-Trp-Gln-Arg-NH₂

The chemical synthesis of 4-N-carboxybutyl-5-fluorocytosine (II) in solution phase starting from 5-fluorocytosine and the solid phase synthesis of Arg-Gln-Trp-Arg-Arg-Trp-Trp-Gln-Arg-NH(2) attached to the 4-N-carboxybutyl-5-fluorocytosine residue at the N-terminus of the peptide (III) via peptide bond formation is reported. The target compound exhibited a significant cytotoxic activity against a culture of HepG2 cells. In addition our results demonstrated that this new compound affect cell viability, produce mitochondrial dysfunction as well as interfere with intracellular calcium homeostasis control; leading to cell malfunction and death.     

Impact of Risk Factors on Different Interval Cancer Subtypes in a Population-Based Breast Cancer Screening Programme

Background

Interval cancers are primary breast cancers diagnosed in women after a negative screening test and before the next screening invitation. Our aim was to evaluate risk factors for interval cancer and their subtypes and to compare the risk factors identified with those associated with incident screen-detected cancers.

Methods

We analyzed data from 645,764 women participating in the Spanish breast cancer screening program from 2000–2006 and followed-up until 2009. A total of 5,309 screen-detected and 1,653 interval cancers were diagnosed. Among the latter, 1,012 could be classified on the basis of findings in screening and diagnostic mammograms, consisting of 489 true interval cancers (48.2%), 235 false-negatives (23.2%), 172 minimal-signs (17.2%) and 114 occult tumors (11.3%). Information on the screening protocol and women''s characteristics were obtained from the screening program registry. Cause-specific Cox regression models were used to estimate the hazard ratios (HR) of risks factors for interval cancer and incident screen-detected cancer. A multinomial regression model, using screen-detected tumors as a reference group, was used to assess the effect of breast density and other factors on the occurrence of interval cancer subtypes.

Results

A previous false-positive was the main risk factor for interval cancer (HR = 2.71, 95%CI: 2.28–3.23); this risk was higher for false-negatives (HR = 8.79, 95%CI: 6.24–12.40) than for true interval cancer (HR = 2.26, 95%CI: 1.59–3.21). A family history of breast cancer was associated with true intervals (HR = 2.11, 95%CI: 1.60–2.78), previous benign biopsy with a false-negatives (HR = 1.83, 95%CI: 1.23–2.71). High breast density was mainly associated with occult tumors (RRR = 4.92, 95%CI: 2.58–9.38), followed by true intervals (RRR = 1.67, 95%CI: 1.18–2.36) and false-negatives (RRR = 1.58, 95%CI: 1.00–2.49).

Conclusion

The role of women''s characteristics differs among interval cancer subtypes. This information could be useful to improve effectiveness of breast cancer screening programmes and to better classify subgroups of women with different risks of developing cancer.     

Cancer genomics identifies disrupted epigenetic genes

Latest advances in genome technologies have greatly advanced the discovery of epigenetic genes altered in cancer. The initial single candidate gene approaches have been coupled with newly developed epigenomic platforms to hasten the convergence of scientific discoveries and translational applications. Here, we present an overview of the evolution of cancer epigenomics and an updated catalog of disruptions in epigenetic pathways, whose misregulation can culminate in cancer. The creation of these basic mutational catalogs in cell lines and primary tumors will provide us with enough knowledge to move diagnostics and therapy from the laboratory bench to the bedside.     

Bird and bat predation services in tropical forests and agroforestry landscapes

Understanding distribution patterns and multitrophic interactions is critical for managing bat‐ and bird‐mediated ecosystem services such as the suppression of pest and non‐pest arthropods. Despite the ecological and economic importance of bats and birds in tropical forests, agroforestry systems, and agricultural systems mixed with natural forest, a systematic review of their impact is still missing. A growing number of bird and bat exclosure experiments has improved our knowledge allowing new conclusions regarding their roles in food webs and associated ecosystem services. Here, we review the distribution patterns of insectivorous birds and bats, their local and landscape drivers, and their effects on trophic cascades in tropical ecosystems. We report that for birds but not bats community composition and relative importance of functional groups changes conspicuously from forests to habitats including both agricultural areas and forests, here termed ‘forest‐agri’ habitats, with reduced representation of insectivores in the latter. In contrast to previous theory regarding trophic cascade strength, we find that birds and bats reduce the density and biomass of arthropods in the tropics with effect sizes similar to those in temperate and boreal communities. The relative importance of birds versus bats in regulating pest abundances varies with season, geography and management. Birds and bats may even suppress tropical arthropod outbreaks, although positive effects on plant growth are not always reported. As both bats and birds are major agents of pest suppression, a better understanding of the local and landscape factors driving the variability of their impact is needed.