Search results for "ELS"
showing 10 items of 12690 documents
Reconstructing the deep population history of Central and South America
2018
We report genome-wide ancient DNA from 49 individuals forming four parallel time transects in Belize, Brazil, the Central Andes, and the Southern Cone, each dating to at least ∼9,000 years ago. The common ancestral population radiated rapidly from just one of the two early branches that contributed to Native Americans today. We document two previously unappreciated streams of gene flow between North and South America. One affected the Central Andes by ∼4,200 years ago, while the other explains an affinity between the oldest North American genome associated with the Clovis culture and the oldest Central and South Americans from Chile, Brazil, and Belize. However, this was not the primary sou…
Genetics and Gene Therapy of Anderson-Fabry Disease.
2018
Fabry's disease is a genetic disorder of X-linked inheritance caused by mutations in the alpha galactosidase A gene resulting in deficiency of this lysosomal enzyme. The progressive accumulation of glycosphingolipids, caused by the inadequate enzymatic activity, is responsible of organ dysfunction and thus of clinical manifestations. In the presence of a high clinical suspicion, a careful physical examination and specific laboratory tests are required, finally diagnosis of Fabry's disease is confirmed by the demonstration of absence or reduced alpha-galactosidase A enzyme activity in hemizygous men and gene typing in heterozygous females; in fact the performance of enzymatic activity assay …
Molecular disturbance underlies to arrhythmogenic cardiomyopathy induced by transgene content, age and exercise in a truncated PKP2 mouse model
2016
13 páginas, 9 tablas, 2 figuras. Contiene material suplementario.
Inducible knockdown of procollagen I protects mice from liver fibrosis and leads to dysregulated matrix genes and attenuated inflammation.
2017
Organ fibrosis is characterized by a chronic wound-healing response, with excess deposition of extracellular matrix components. Here, collagen type I represents the most abundant scar component and a primary target for antifibrotic therapies. Liver fibrosis can progress to cirrhosis and primary liver cancer, which are the major causes of liver related morbidity and mortality. However, a (pro-)collagen type I specific therapy remains difficult and its therapeutic abrogation may incur unwanted side effects. We therefore designed tetracycline-regulated procollagen alpha1(I) short hairpin (sh)RNA expressing mice that permit a highly efficient inducible knockdown of the procollagen alpha1(I) gen…
Shifts in gut microbiota composition in an APP/PSS1 transgenic mouse model of Alzheimer's disease during lifespan.
2017
Alzheimer's disease (AD) is the most common form of dementia and one of the major causes of disability and dependency in older people. Accumulating evidences link gut microbiota with different diseases and its relationship with neurodegenerative diseases is becoming most intriguing. This study was aimed to compare the gut microbiota of transgenic APP/PS1 (TG) mice, a well‐established deterministic mouse model of AD, with their C57BL/6 wild‐type (WT) littermates. Faecal samples were collected from 3‐, 6‐ and 24‐month‐old mice and analysed by pyrosequencing of the V1–V3 region of the bacterial 16S rRNA genes. Bacterial profiles were similar in all young mice (3 months old), and started to div…
Behavioral fragmentation in the D1CT-7 mouse model of Tourette's syndrome.
2017
Aim The transgenic D1CT-7 mouse is one of the best-characterized animal models of Tourette's syndrome (TS), exhibiting spontaneous tic-like Head-Body Twitches (HBT) and deficits in sensorimotor gating. This study is aimed at evaluating the behavioral dynamics of these mutants and their potential relevance to TS. Methods The behavior of D1CT-7 and Wild Type littermates was firstly assessed by considering frequencies and durations. To detect recurrent real-time behavioral sequences, the multivariate T-pattern analysis was employed. Analyses of transition probabilities among behaviors further provided an overall picture of the behavioral dynamics. Results T-patterns and transition matrices rev…
Gradual development of psoriatic skin lesions by constitutive low-level expression of IL-17A
2016
Psoriasis is a common chronic inflammatory skin disease restricted to humans. The understanding of its pathogenesis has long been hampered by the lack of suitable chronic mouse models. The cytokine IL-17A has emerged as a key player in epithelial immune responses and the defense against extracellular pathogens. Moreover, enhanced expression of IL-17A can turn pathologic and is closely associated with psoriasis. In this study, we generated a novel transgenic mouse model that recapitulates many characteristics of psoriasis. DC-1L-17A(ind) mice with constitutive low-level expression of IL-17A by CD11c(+) cells gradually develop skin lesions during adult life. The lesions preferentially occur a…
Model-based design of RNA hybridization networks implemented in living cells
2017
[EN] Synthetic gene circuits allow the behavior of living cells to be reprogrammed, and non-coding small RNAs (sRNAs) are increasingly being used as programmable regulators of gene expression. However, sRNAs (natural or synthetic) are generally used to regulate single target genes, while complex dynamic behaviors would require networks of sRNAs regulating each other. Here, we report a strategy for implementing such networks that exploits hybridization reactions carried out exclusively by multifaceted sRNAs that are both targets of and triggers for other sRNAs. These networks are ultimately coupled to the control of gene expression. We relied on a thermo-dynamic model of the different stable…
The dark side of centromeres: types, causes and consequences of structural abnormalities implicating centromeric DNA
2018
Centromeres are the chromosomal domains required to ensure faithful transmission of the genome during cell division. They have a central role in preventing aneuploidy, by orchestrating the assembly of several components required for chromosome separation. However, centromeres also adopt a complex structure that makes them susceptible to being sites of chromosome rearrangements. Therefore, preservation of centromere integrity is a difficult, but important task for the cell. In this review, we discuss how centromeres could potentially be a source of genome instability and how centromere aberrations and rearrangements are linked with human diseases such as cancer.
Inhibition of DNA damage response at telomeres improves the detrimental phenotypes of Hutchinson–Gilford Progeria Syndrome
2019
Hutchinson–Gilford progeria syndrome (HGPS) is a genetic disorder characterized by premature aging features. Cells from HGPS patients express progerin, a truncated form of Lamin A, which perturbs cellular homeostasis leading to nuclear shape alterations, genome instability, heterochromatin loss, telomere dysfunction and premature entry into cellular senescence. Recently, we reported that telomere dysfunction induces the transcription of telomeric non-coding RNAs (tncRNAs) which control the DNA damage response (DDR) at dysfunctional telomeres. Here we show that progerin-induced telomere dysfunction induces the transcription of tncRNAs. Their functional inhibition by sequence-specific telomer…