The effects of wrench-dominated basement-involved faults on folding of overlying strata in the Bahregansar anticline, western Persian Gulf, Iran

Basement-involved fault geometry and kinematics has a systematic effect on the structural style of the tectonic setting. In this study, 2D and 3D seismic datasets, well data as well as thickness and depth maps were utilized to consider and reconstruct the characteristics and effects of the wrench-dominated basement-involved fault underlying the Bahregansar anticline, which is a gentle, elongated and NW–SE-trending structure in the NW Persian Gulf, on the nature of its folded strata. Moreover, using the 2D sequential restoration, the deformation of the basement structural features was modelled and analysed for its influence on the reactivation of faulting. The results show that the major basement-involved fault, called the Hendijan–Bahregansar–Nowrooz Fault (HBNF), extends along the NE–SW-trending orientation and consist of several key anticlines. The structural evolution of the Bahregansar anticline has been deeply affected by Turonian folding phase and Pliocene Zagros orogeny associated with the HBNF. In the Upper Cretaceous, the HBNF propagated upward through the overlying sedimentary sequences when the inherited normal fault contractionally reactivated in the sinistral-reverse sense as the transpression zone in response to the Neo-Tethys oceanic plate subduction under the Eurasian plate. In this regard, the NNE–SSW-trending Bahregansar anticline (i.e., Arabian trend) formed as a forced fold. Continuing oblique convergence and associated deformation was accommodated by a change in the HBNF displacement sense from sinistral to dextral movement and buckling of the Bahregansar anticline as a result of the Pliocene Zagros orogeny

The effects of wrench-dominated basement-involved faults on folding of overlying strata in the Bahregansar anticline, western Persian Gulf, Iran

Basement-involved fault geometry and kinematics has a systematic effect on the structural style of the tectonic setting. In this study, 2D and 3D seismic datasets, well data as well as thickness and depth maps were utilized to consider and reconstruct the characteristics and effects of the wrench-dominated basement-involved fault underlying the Bahregansar anticline, which is a gentle, elongated and NW–SE-trending structure in the NW Persian Gulf, on the nature of its folded strata. Moreover, using the 2D sequential restoration, the deformation of the basement structural features was modelled and analysed for its influence on the reactivation of faulting. The results show that the major basement-involved fault, called the Hendijan–Bahregansar–Nowrooz Fault (HBNF), extends along the NE–SW-trending orientation and consist of several key anticlines. The structural evolution of the Bahregansar anticline has been deeply affected by Turonian folding phase and Pliocene Zagros orogeny associated with the HBNF. In the Upper Cretaceous, the HBNF propagated upward through the overlying sedimentary sequences when the inherited normal fault contractionally reactivated in the sinistral-reverse sense as the transpression zone in response to the Neo-Tethys oceanic plate subduction under the Eurasian plate. In this regard, the NNE–SSW-trending Bahregansar anticline (i.e., Arabian trend) formed as a forced fold. Continuing oblique convergence and associated deformation was accommodated by a change in the HBNF displacement sense from sinistral to dextral movement and buckling of the Bahregansar anticline as a result of the Pliocene Zagros orogeny

Understanding the role of décollement thickness on the evolution of décollement folds: insights from discrete element models

We explored the influence of a variety of geometric and mechanical factors in the evolution of décollement folds above a weak décollement level in a sedimentary sequence. Under an applied overburden pressure, we construct nine discrete element models (DE-models) to test the effects of mechanical stratigraphy, the thickness of the décollement layer, and the number of strong and weak layers within the sedimentary cover sequence. The effects of the aforementioned parameters on the structural style of fold belts and the mechanical evolution of décollement folds that develop during a progressive deformation are what we are searching for. The one-way lateral motion of a rigid, vertical boundary wall was used to shorten the particle assemblage. The models presented in this study were then compared to a natural structure in Iran and demonstrated that the combined effects of mechanical behaviour, the thickness of décollement layer, and the number of strong and weak layers within the sedimentary cover sequence are playing the decisive role in the structural style, kinematic and mechanical evolution of décollement folds

Understanding the role of décollement thickness on the evolution of décollement folds: insights from discrete element models

We explored the influence of a variety of geometric and mechanical factors in the evolution of décollement folds above a weak décollement level in a sedimentary sequence. Under an applied overburden pressure, we construct nine discrete element models (DE-models) to test the effects of mechanical stratigraphy, the thickness of the décollement layer, and the number of strong and weak layers within the sedimentary cover sequence. The effects of the aforementioned parameters on the structural style of fold belts and the mechanical evolution of décollement folds that develop during a progressive deformation are what we are searching for. The one-way lateral motion of a rigid, vertical boundary wall was used to shorten the particle assemblage. The models presented in this study were then compared to a natural structure in Iran and demonstrated that the combined effects of mechanical behaviour, the thickness of décollement layer, and the number of strong and weak layers within the sedimentary cover sequence are playing the decisive role in the structural style, kinematic and mechanical evolution of décollement folds

Everolimus, a mammalian target of rapamycin inhibitor, ameliorated streptozotocin-induced learning and memory deficits via neurochemical alterations in male rats

Everolimus (EVR), as a rapamycin analog, is a selective inhibitor of the mammalian target of rapamycin (mTOR) kinase and its associated signaling pathway. mTOR is a serine/threonine protein kinase and its hyperactivity is involved in the pathophysiology of Alzheimer’s disease (AD) and associated cognitive deficits. The present study evaluated the impact of EVR, on cognitive functions, hippocampal cell loss, and neurochemical parameters in the intracerebroventricular streptozotocin (icv-STZ) model of AD rats. EVR (1 and 5 mg/kg) was administered for 21 days following the single administration of STZ (3 mg/kg, icv) or for 7 days on days 21-28 post-STZ injection after establishment of cognitive dysfunction. Cognitive deficits (passive avoidance and spatial memory), oxidative stress parameters, acetylcholinesterase (AChE) activity, and percentage of cell loss were evaluated in the hippocampus. Chronic administration (1 and 5 mg/kg for 21 days from the day of surgery and icv-STZ infusion) or acute injection (5 mg/kg for 7 days after establishment of cognitive impairment) of EVR significantly attenuated cognitive dysfunction, neuronal loss, oxidative stress and AChE activity in the hippocampus of STZ-AD rats. In conclusion, our study showed that EVR could prevent or improve deteriorations in behavioral, biochemical and histopathological features of the icv-STZ rat model of AD. Therefore, inhibition of the hyperactivated mTOR may be an important therapeutic target for AD

Cost-of-Illness Analysis of Type 2 Diabetes Mellitus in Iran

Diabetes is a worldwide high prevalence chronic progressive disease that poses a significant challenge to healthcare systems. The aim of this study is to provide a detailed economic burden of diagnosed type 2 diabetes mellitus (T2DM) and its complications in Iran in 2009 year.This is a prevalence-based cost-of-illness study focusing on quantifying direct health care costs by bottom-up approach. Data on inpatient hospital services, outpatient clinic visits, physician services, drugs, laboratory test, education and non-medical cost were collected from two national registries. The human capital approach was used to calculate indirect costs separately in male and female and also among different age groups.The total national cost of diagnosed T2DM in 2009 is estimated at 3.78 billion USA dollars (USD) including 2.04±0.28 billion direct (medical and non-medical) costs and indirect costs of 1.73 million. Average direct and indirect cost per capita was 842.6±102 and 864.8 USD respectively. Complications (48.9%) and drugs (23.8%) were main components of direct cost. The largest components of medical expenditures attributed to diabetes's complications are cardiovascular disease (42.3% of total Complications cost), nephropathy (23%) and ophthalmic complications (14%). Indirect costs include temporarily disability (335.7 million), permanent disability (452.4 million) and reduced productivity due to premature mortality (950.3 million).T2DM is a costly disease in the Iran healthcare system and consume more than 8.69% of total health expenditure. In addition to these quantified costs, T2DM imposes high intangible costs on society in terms of reduced quality of life. Identification of effective new strategies for the control of diabetes and its complications is a public health priority

Differential expression of anterior gradient gene AGR2 in prostate cancer

<p>Abstract</p> <p>Background</p> <p>The protein AGR2 is a putative member of the protein disulfide isomerase family and was first identified as a homolog of the <it>Xenopus laevis </it>gene XAG-2. AGR2 has been implicated in a number of human cancers. In particular, AGR2 has previously been found to be one of several genes that encode secreted proteins showing increased expression in prostate cancer cells compared to normal prostatic epithelium.</p> <p>Methods</p> <p>Gene expression levels of AGR2 were examined in prostate cancer cells by microarray analysis. We further examined the relationship of AGR2 protein expression to histopathology and prostate cancer outcome on a population basis using tissue microarray technology.</p> <p>Results</p> <p>At the RNA and protein level, there was an increase in AGR2 expression in adenocarcinoma of the prostate compared to morphologically normal prostatic glandular epithelium. Using a tissue microarray, this enhanced AGR2 expression was seen as early as premalignant PIN lesions. Interestingly, within adenocarcinoma samples, there was a slight trend toward lower levels of AGR2 with increasing Gleason score. Consistent with this, relatively lower levels of AGR2 were highly predictive of disease recurrence in patients who had originally presented with high-stage primary prostate cancer (P = 0.009).</p> <p>Conclusions</p> <p>We have shown for the first time that despite an increase in AGR2 expression in prostate cancer compared to non-malignant cells, relatively lower levels of AGR2 are highly predictive of disease recurrence following radical prostatectomy.</p

The clinical and genetic spectrum of autosomal-recessive TOR1A-related disorders.

In the field of rare diseases, progress in molecular diagnostics led to the recognition that variants linked to autosomal-dominant neurodegenerative diseases of later onset can, in the context of biallelic inheritance, cause devastating neurodevelopmental disorders and infantile or childhood-onset neurodegeneration. TOR1A-associated arthrogryposis multiplex congenita 5 (AMC5) is a rare neurodevelopmental disorder arising from biallelic variants in TOR1A, a gene that in the heterozygous state is associated to torsion dystonia-1 (DYT1 or DYT-TOR1A), an early-onset dystonia with reduced penetrance. While 15 individuals with TOR1A-AMC5 have been reported (less than 10 in detail), a systematic investigation of the full disease-associated spectrum has not been conducted. Here, we assess the clinical, radiological and molecular characteristics of 57 individuals from 40 families with biallelic variants in TOR1A. Median age at last follow-up was 3 years (0-24 years). Most individuals presented with severe congenital flexion contractures (95%) and variable developmental delay (79%). Motor symptoms were reported in 79% and included lower limb spasticity and pyramidal signs, as well as gait disturbances. Facial dysmorphism was an integral part of the phenotype, with key features being a broad/full nasal tip, narrowing of the forehead and full cheeks. Analysis of disease-associated manifestations delineated a phenotypic spectrum ranging from normal cognition and mild gait disturbance to congenital arthrogryposis, global developmental delay, intellectual disability, absent speech and inability to walk. In a subset, the presentation was consistent with fetal akinesia deformation sequence with severe intrauterine abnormalities. Survival was 71% with higher mortality in males. Death occurred at a median age of 1.2 months (1 week - 9 years) due to respiratory failure, cardiac arrest, or sepsis. Analysis of brain MRI studies identified non-specific neuroimaging features, including a hypoplastic corpus callosum (72%), foci of signal abnormality in the subcortical and periventricular white matter (55%), diffuse white matter volume loss (45%), mega cisterna magna (36%) and arachnoid cysts (27%). The molecular spectrum included 22 distinct variants, defining a mutational hotspot in the C-terminal domain of the Torsin-1A protein. Genotype-phenotype analysis revealed an association of missense variants in the 3-helix bundle domain to an attenuated phenotype, while missense variants near the Walker A/B motif as well as biallelic truncating variants were linked to early death. In summary, this systematic cross-sectional analysis of a large cohort of individuals with biallelic TOR1A variants across a wide age-range delineates the clinical and genetic spectrum of TOR1A-related autosomal-recessive disease and highlights potential predictors for disease severity and survival

Biallelic MED27 variants lead to variable ponto-cerebello-lental degeneration with movement disorders

MED27 is a subunit of the Mediator multiprotein complex, which is involved in transcriptional regulation. Biallelic MED27 variants have recently been suggested to be responsible for an autosomal recessive neurodevelopmental disorder with spasticity, cataracts and cerebellar hypoplasia. We further delineate the clinical phenotype of MED27-related disease by characterizing the clinical and radiological features of 57 affected individuals from 30 unrelated families with biallelic MED27 variants. Using exome sequencing and extensive international genetic data sharing, 39 unpublished affected individuals from 18 independent families with biallelic missense variants in MED27 have been identified (29 females, mean age at last follow-up 17 ± 12.4 years, range 0.1-45). Follow-up and hitherto unreported clinical features were obtained from the published 12 families. Brain MRI scans from 34 cases were reviewed. MED27-related disease manifests as a broad phenotypic continuum ranging from developmental and epileptic-dyskinetic encephalopathy to variable neurodevelopmental disorder with movement abnormalities. It is characterized by mild to profound global developmental delay/intellectual disability (100%), bilateral cataracts (89%), infantile hypotonia (74%), microcephaly (62%), gait ataxia (63%), dystonia (61%), variably combined with epilepsy (50%), limb spasticity (51%), facial dysmorphism (38%) and death before reaching adulthood (16%). Brain MRI revealed cerebellar atrophy (100%), white matter volume loss (76.4%), pontine hypoplasia (47.2%) and basal ganglia atrophy with signal alterations (44.4%). Previously unreported 39 affected individuals had seven homozygous pathogenic missense MED27 variants, five of which were recurrent. An emerging genotype-phenotype correlation was observed. This study provides a comprehensive clinical-radiological description of MED27-related disease, establishes genotype-phenotype and clinical-radiological correlations and suggests a differential diagnosis with syndromes of cerebello-lental neurodegeneration and other subtypes of 'neuro-MEDopathies'