Search results for "IFT"
showing 10 items of 2193 documents
The cytoprotective protein MANF promotes neuronal survival independently from its role as a GRP78 cofactor
2021
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-stress-regulated protein exhibiting cytoprotective properties through a poorly understood mechanism in various in vitro and in vivo models of neuronal and non-neuronal damage. Although initially characterized as a secreted neurotrophic factor for midbrain dopamine neurons, MANF has recently gained more interest for its intracellular role in regulating the ER homeostasis, including serving as a cofactor of the chaperone glucose-regulated protein 78 (GRP78). We aimed for a better understanding of the neuroprotective mechanisms of MANF. Here we show for the first time that MANF promotes the survival of …
The genomic footprint of climate adaptation inChironomus riparius
2017
The gradual heterogeneity of climatic factors produces continuously varying selection pressures across geographic distances that leave signatures of clinal variation in the genome. Separating signatures of clinal adaptation from signatures of other evolutionary forces, such as demographic processes, genetic drift, and adaptation to specific non-clinal conditions of the immediate local environment is a major challenge. Here, we examine climate adaptation in five natural populations of the non-biting midge Chironomus riparius sampled along a climatic gradient across Europe. Our study integrates experimental data, individual genome resequencing, Pool-Seq data, and population genetic modelling.…
Scientific Reports
2019
Anthropogenic climate change ranks among the major global-scale threats to modern biodiversity. Extinction risks are known to increase via the interactions between rapid climatic alterations and environmentally-sensitive species traits that fail to adapt to those changes. Accumulating evidence reveals the influence of ecophysiological, ecological and phenological factors as drivers underlying demographic collapses that lead to population extinctions. However, the extent to which life-history traits influence population responses to climate change remains largely unexplored. The emerging 'cul-de-sac hypothesis' predicts that reptilian viviparity ('live-bearing' reproduction), a 'key innovati…
DEBATE: Do interventions based on behavioral theory work in the real world?
2019
Abstract Background Behavioral scientists suggest that for behavior change interventions to work effectively, and deliver population-level health outcomes, they must be underpinned by behavioral theory. However, despite implementation of such interventions, population levels of both health outcomes and linked behaviors have remained relatively static. We debate the extent to which interventions based on behavioral theory work in the real world to address population health outcomes. Discussion Hagger argues there is substantive evidence supporting the efficacy and effectiveness of interventions based on behavioral theory in promoting population-level health behavior change in the ‘real world…
Molecular surveillance of norovirus, 2005–16 : an epidemiological analysis of data collected from the NoroNet network
2018
BACKGROUND: The development of a vaccine for norovirus requires a detailed understanding of global genetic diversity of noroviruses. We analysed their epidemiology and diversity using surveillance data from the NoroNet network.METHODS: We included genetic sequences of norovirus specimens obtained from outbreak investigations and sporadic gastroenteritis cases between 2005 and 2016 in Europe, Asia, Oceania, and Africa. We genotyped norovirus sequences and analysed sequences that overlapped at open reading frame (ORF) 1 and ORF2. Additionally, we assessed the sampling date and country of origin of the first reported sequence to assess when and where novel drift variants originated.FINDINGS: W…
STAG1 mutations cause a novel cohesinopathy characterised by unspecific syndromic intellectual disability
2017
Item does not contain fulltext BACKGROUND: Cohesinopathies are rare neurodevelopmental disorders arising from a dysfunction in the cohesin pathway, which enables chromosome segregation and regulates gene transcription. So far, eight genes from this pathway have been reported in human disease. STAG1 belongs to the STAG subunit of the core cohesin complex, along with five other subunits. This work aimed to identify the phenotype ascribed to STAG1 mutations. METHODS: Among patients referred for intellectual disability (ID) in genetics departments worldwide, array-comparative genomic hybridisation (CGH), gene panel, whole-exome sequencing or whole-genome sequencing were performed following the …
A Novel Role for CSRP1 in a Lebanese Family with Congenital Cardiac Defects
2017
Despite an obvious role for consanguinity in congenital heart disease (CHD), most studies fail to document a monogenic model of inheritance except for few cases. We hereby describe a first-degree cousins consanguineous Lebanese family with 7 conceived children: 2 died in utero of unknown causes, 3 have CHD, and 4 have polydactyly. The aim of the study is to unveil the genetic variant(s) causing these phenotypes using next generation sequencing (NGS) technology. Targeted exome sequencing identified a heterozygous duplication in CSRP1 which leads to a potential frameshift mutation at position 154 of the protein. This mutation is inherited from the father, and segregates only with the CHD phen…
Chance and necessity in the genome evolution of endosymbiotic bacteria of insects.
2017
An open question in evolutionary biology is how does the selection–drift balance determine the fates of biological interactions. We searched for signatures of selection and drift in genomes of five endosymbiotic bacterial groups known to evolve under strong genetic drift. Although most genes in endosymbiotic bacteria showed evidence of relaxed purifying selection, many genes in these bacteria exhibited stronger selective constraints than their orthologs in free-living bacterial relatives. Remarkably, most of these highly constrained genes had no role in the host–symbiont interactions but were involved in either buffering the deleterious consequences of drift or other host-unrelated function…
Evolutionary impact of copy number variation rates.
2017
[Objective]: Copy number variation is now recognized as one of the major sources of genetic variation among individuals in natural populations of any species. However, the relevance of these unexpected observations goes beyond diagnosing high diversity. [Results]: Here, it is argued that the molecular rates of copy number variation, mainly the deletion rate upon variation, determine the evolutionary road of the genome regarding size. Genetic drift will govern this process only if the efective population size is lower than the inverse of the deletion rate. Otherwise, natural selection will do.
Exome-wide somatic mutation characterization of small bowel adenocarcinoma
2018
Small bowel adenocarcinoma (SBA) is an aggressive disease with limited treatment options. Despite previous studies, its molecular genetic background has remained somewhat elusive. To comprehensively characterize the mutational landscape of this tumor type, and to identify possible targets of treatment, we conducted the first large exome sequencing study on a population-based set of SBA samples from all three small bowel segments. Archival tissue from 106 primary tumors with appropriate clinical information were available for exome sequencing from a patient series consisting of a majority of confirmed SBA cases diagnosed in Finland between the years 2003–2011. Paired-end exome sequencing was…