Search results for "pea"
showing 10 items of 6599 documents
Ancient European dog genomes reveal continuity since the Early Neolithic
2017
Europe has played a major role in dog evolution, harbouring the oldest uncontested Palaeolithic remains and having been the centre of modern dog breed creation. Here we sequence the genomes of an Early and End Neolithic dog from Germany, including a sample associated with an early European farming community. Both dogs demonstrate continuity with each other and predominantly share ancestry with modern European dogs, contradicting a previously suggested Late Neolithic population replacement. We find no genetic evidence to support the recent hypothesis proposing dual origins of dog domestication. By calibrating the mutation rate using our oldest dog, we narrow the timing of dog domestication t…
Population Genetics of Latvians in the Context of Admixture between North-Eastern European Ethnic Groups
2018
Abstract This article presents a review on population genetics of Latvians, which alongside Lithuanians are the two extant Baltic speaking populations. The article provides a description of genome-wide single nucleotide polymorphism (SNP) data and contains a comparative analysis of the results of studies performed on classical autosomal genetic markers, mitochondrial DNA (mtDNA) and the non-recombining part of the Y chromosome (NRY), with data on neighbouring populations. The study also covers data of recently performed ancient DNA (aDNA) studies carried out on samples from the territory of today’s Latvia. The results of population genetic studies have shown a mixture of eastern and western…
rbFOX1/MBNL1 competition for CCUG RNA repeats binding contributes to myotonic dystrophy type 1/type 2 differences
2018
Myotonic dystrophy type 1 and type 2 (DM1, DM2) are caused by expansions of CTG and CCTG repeats, respectively. RNAs containing expanded CUG or CCUG repeats interfere with the metabolism of other RNAs through titration of the Muscleblind-like (MBNL) RNA binding proteins. DM2 follows a more favorable clinical course than DM1, suggesting that specific modifiers may modulate DM severity. Here, we report that the rbFOX1 RNA binding protein binds to expanded CCUG RNA repeats, but not to expanded CUG RNA repeats. Interestingly, rbFOX1 competes with MBNL1 for binding to CCUG expanded repeats and overexpression of rbFOX1 partly releases MBNL1 from sequestration within CCUG RNA foci in DM2 muscle ce…
Evolving Notch polyQ tracts reveal possible solenoid interference elements.
2016
ABSTRACTPolyglutamine (polyQ) tracts in regulatory proteins are extremely polymorphic. As functional elements under selection for length, triplet repeats are prone to DNA replication slippage and indel mutations. Many polyQ tracts are also embedded within intrinsically disordered domains, which are less constrained, fast evolving, and difficult to characterize. To identify structural principles underlying polyQ tracts in disordered regulatory domains, here I analyze deep evolution of metazoan Notch polyQ tracts, which can generate alleles causing developmental and neurogenic defects. I show that Notch features polyQ tract turnover that is restricted to a discrete number of conserved “polyQ …
In silico discovery of substituted pyrido[2,3-d]pyrimidines and pentamidine-like compounds with biological activity in myotonic dystrophy models
2016
Myotonic dystrophy type 1 (DM1) is a rare multisystemic disorder associated with an expansion of CUG repeats in mutant DMPK (dystrophia myotonica protein kinase) transcripts; the main effect of these expansions is the induction of pre-mRNA splicing defects by sequestering muscleblind-like family proteins (e.g. MBNL1). Disruption of the CUG repeats and the MBNL1 protein complex has been established as the best therapeutic approach for DM1, hence two main strategies have been proposed: targeted degradation of mutant DMPK transcripts and the development of CUG-binding molecules that prevent MBNL1 sequestration. Herein, suitable CUG-binding small molecules were selected using in silico approach…
The shared frameshift mutation landscape of microsatellite-unstable cancers suggests immunoediting during tumor evolution
2020
The immune system can recognize and attack cancer cells, especially those with a high load of mutation-induced neoantigens. Such neoantigens are abundant in DNA mismatch repair (MMR)-deficient, microsatellite-unstable (MSI) cancers. MMR deficiency leads to insertion/deletion (indel) mutations at coding microsatellites (cMS) and to neoantigen-inducing translational frameshifts. Here, we develop a tool to quantify frameshift mutations in MSI colorectal and endometrial cancer. Our results show that frameshift mutation frequency is negatively correlated to the predicted immunogenicity of the resulting peptides, suggesting counterselection of cell clones with highly immunogenic frameshift peptid…
Anisakis sensitization in different population groups and public health impact. A systematic review
2018
Anisakis simplex spp. sensitization rates have increased worldwide, with a significant impact on health-care systems. To date, no clear-cut diagnostic criteria and laboratory algorithm have been established, so anisakiasis still represents an under-reported health problem whose clinical manifestations, when present, mimic the much more common allergic and digestive disorders. Aim of the study was to systematically review the available literature on the prevalence of sensitization against Anisakis in the general population and in specific population groups, taking into account the impact of the different available diagnostic techniques on the epidemiological data. Following the Preferred Rep…
Brain anatomy of the 4‐day‐old European rabbit
2018
International audience; The European rabbit (Oryctolagus cuniculus) is a widely used model in fundamental, medical and veterinary neurosciences. Besides investigations in adults, rabbit pups are relevant to study perinatal neurodevelopment and early behaviour. To date, the rabbit is also the only species in which a pheromone - the mammary pheromone (MP) - emitted by lactating females and active on neonatal adaptation has been described. The MP is crucial since it contributes directly to nipple localisation and oral seizing in neonates, i.e. to their sucking success. It may also be one of the non-photic cues arising from the mother, which stimulates synchronisation of the circadian system du…
High-risk soft tissue sarcomas treated with perioperative chemotherapy: Improving prognostic classification in a randomised clinical trial
2018
Background: Patients with extremity and trunk wall soft tissue sarcoma (STS) with high malignancy grade and size >5 cm are at high-risk of death. This risk varies depending also on other patient and tumour features, including histologic subtype. This study investigated whether a prognostic nomogram can improve risk assessment of these patients. Methods: Data from high-risk STS patients enrolled in a randomised controlled trial investigating different perioperative chemotherapy regimens were analysed. Ten-year probability of overall survival (OS) and incidence of distant metastasis (DM) were computed using the prognostic nomogram Sarculator (pr-OS and inc-DM, respectively). Tumour response a…
Multi-centre validation of a flow cytometry method to identify optimal responders to interferon-beta in multiple sclerosis.
2018
Background and objectives: Percentages of blood CD19 + CD5 + B cells and CD8 + perforin + T lymphocytes can predict response to Interferon (IFN)-beta treatment in relapsing-remitting multiple sclerosis (RRMS) patients. We aimed to standardize their detection in a multicenter study, prior to their implementation in clinical practice. Methods: Fourteen hospitals participated in the study. A reference centre was established for comparison studies. Peripheral blood cells of 105 untreated RRMS patients were studied. Every sample was analyzed in duplicate in the participating centre and in the reference one by flow cytometry. When needed, participating centres corrected fluorescence compensations…