A compressive system overimposed to an oblique rift: Applications in the Malargüe fold and thrust belt, southern Mendoza

Se llevaron a cabo modelos análogos para simular la evolución resultante de la aplicación de esfuerzos compresivos oblicuos al eje de un sistema extensional preexistente. Se utilizaron materiales granulares para representar rocas frágiles de la corteza superior. En la base de los modelos se indujo la formación de dos hemigrábenes asimétricos y de una falla de transferencia entre ambos, para luego comprimir el sistema desplazando un pistón en sentido oblicuo al rumbo de los hemigrábenes. El objetivo de estos experimentos fue analizar el arreglo estructural resultante a partir de un cambio de régimen tectónico, estudiando la influencia que ejercen las estructuras extensionales preexistentes sobre el estilo de la deformación compresiva sobreimpuesta. Aunque los resultados obtenidos muestran que la reactivación de las fallas normales es mínima, su presencia ejerce un fuerte control geométrico en el arreglo final de las fallas inversas. Al aumentar la distancia entre el sistema extensional subyacente y el frente de empuje, el control sobre los corrimientos generados se pierde. Asociados al control estructural impuesto se encontraron cambios de rumbo de los corrimientos, variaciones en las dimensiones de las láminas de corrimiento, levantamientos diferenciales en sectores próximos a la estructura subyacente y formación de corrimientos fuera de secuencia en sectores determinados del sistema. Estos resultados fueron comparados con la arquitectura estructural del sector sur de la faja plegada y corrida de Malargüe, sugiriendo analogías que permiten interpretar la presencia de trenes de extensión de orientación NE y NO durante el evento extensivo jurásico en esta región.Analogue modelling experiments were performed to simulate the evolution that results from the application of compressive stresses oblique to the axis of a pre-existing extensional system. Granular materials were used to represent brittle upper crustal rocks. Two asymmetric halfgrabens linked by a transfer fault were created in the base of the models, and were subsequently compressed moving a piston in oblique sense to the halfgrabens' strike. The aim of these experiments was to analyze the structural pattern that results from a change of tectonic regime, studying the influence that exerts the preexisting extensional structures over the style of latter compressive deformation. Even though the obtained results show limited reactivation of normal faults, the final geometric arrangement of the new reverse faults was strongly controlled by them. Increasing the distance between the underlying extensional system and the advancing thrust front results in a loss of its influence over the newly formed thrusts. Associated with the imposed structural control, strike changes of the thrusts, length variations of the thrust sheets, differential uplifting near the basal structure and out of sequence thrusting localized in certain sectors of the system were found. These results have been compared with the structural architecture of the southern sector of the Malargüe fold and thrust belt, suggesting analogies that allow interpreting the presence of NE and NW oriented extensional trends for the Jurassic extensional event in this regionFil: Yagupsky, Daniel Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; ArgentinaFil: Cristallini, Ernesto Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; ArgentinaFil: Zamora Valcarce, Gonzalo. Repsol YPF; ArgentinaFil: Varadé, Roberto. Repsol YPF; Argentin

TRAIL/TRAIL Receptor System and Susceptibility to Multiple Sclerosis

The TNF-related apoptosis inducing ligand (TRAIL)/TRAIL receptor system participates in crucial steps in immune cell activation or differentiation. It is able to inhibit proliferation and activation of T cells and to induce apoptosis of neurons and oligodendrocytes, and seems to be implicated in autoimmune diseases. Thus, TRAIL and TRAIL receptor genes are potential candidates for involvement in susceptibility to multiple sclerosis (MS). To test whether single-nucleotide polymorphisms (SNPs) in the human genes encoding TRAIL, TRAILR-1, TRAILR-2, TRAILR-3 and TRAILR-4 are associated with MS susceptibility, we performed a candidate gene case-control study in the Spanish population. 59 SNPs in the TRAIL and TRAIL receptor genes were analysed in 628 MS patients and 660 controls, and validated in an additional cohort of 295 MS patients and 233 controls. Despite none of the SNPs withstood the highly conservative Bonferroni correction, three SNPs showing uncorrected p values<0.05 were successfully replicated: rs4894559 in TRAIL gene, p = 9.8×10−4, OR = 1.34; rs4872077, in TRAILR-1 gene, p = 0.005, OR = 1.72; and rs1001793 in TRAILR-2 gene, p = 0.012, OR = 0.84. The combination of the alleles G/T/A in these SNPs appears to be associated with a reduced risk of developing MS (p = 2.12×10−5, OR = 0.59). These results suggest that genes of the TRAIL/TRAIL receptor system exerts a genetic influence on MS

Oblique half-graben inversion of the Mesozoic Neuquén Rift in the Malargüe Fold and Thrust Belt, Mendoza, Argentina: New insights from analogue models

The Malargüe fold and thrust belt, located in the Andean mountains between 34°S and 36°30′S, formed in response to contraction during Cenozoic times. Its structural style and geometry was controlled by the Mesozoic rift system that formed the Neuquén basin in west-central Argentina. The rift architecture in the southern sector of this belt was previously interpreted in terms of the present N-S compressive structural trends, assuming the inversion of pre-existing normal faults with the same orientation. Here, we propose that the NW-SE-trending El Manzano-Liu Cullín lineament, located in the northern termination of the Sierra Azul, reflects the presence of a half-graben master fault in the subsurface. This hypothesis is supported by subsurface data, a balanced cross section, and it is tested using a series of scaled sandbox analogue models. We suggest that the lineament responds to a reactivated NW-trending half-graben fault, hidden by the mainly N-S-trending Andean structures. The proposed orientation is in agreement with the NE-SW extension developed in the Neuquén basin during the Triassic-Early Jurassic. The modeling of the inverted oblique half-graben reveals that the strikes of the main structures of inversion-related belts may often be independent of the orientation of the previously developed extensional system, providing a new perspective for their interpretation.Fil: Yagupsky, Daniel Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; ArgentinaFil: Cristallini, Ernesto Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; ArgentinaFil: Fantín, Julián. Repsol YPF S.A; ArgentinaFil: Valcarce, Gonzalo Zamora. Repsol YPF S.A.; ArgentinaFil: Bottesi, Germán. Repsol YPF; ArgentinaFil: Varadé, Roberto. Repsol YPF; Argentin

Multiple sclerosis retrovirus-like envelope gene: Role of the chromosome 20 insertion

Background: The genetic basis involved in multiple sclerosis (MS) susceptibility was not completely revealed by genome-wide association studies. Part of it could lie in repetitive sequences, as those corresponding to human Endogenous Retroviruses (HERVs). Retrovirus-like particles were isolated from MS patients and the genome of the MS-associated retrovirus (MSRV) was the founder of the HERV-W family. We aimed to ascertain which chromosomal origin encodes the pathogenic ENV protein by genomic analysis of the HERV-W insertions. Methods/results: In silico analyses allowed to uncover putative open reading frames containing the specific sequence previously reported for MSRV-like envelope (env) detection. Out of the 261 genomic insertions of HERV-W env, only 9 copies harbor the specific primers and probe featuring MSRV-like env. The copy from chromosome 20 was further studied considering its size, a truncated homologue of the functional HERV-W env sequence encoding syncytin. High Resolution Melting analysis of this sequence identified two single nucleotide polymorphisms, subsequently genotyped by Taqman chemistry in 668 MS patients and 678 healthy controls. No significant association of these polymorphisms with MS risk was evidenced. Transcriptional activity of this MSRV-like env copy was detected in peripheral blood mononuclear cells from patients and controls. RNA expression levels of chromosome 20-specific MSRV-like env did not show significant differences between MS patients and controls, neither were related to genotypes of the two mentioned polymorphisms. Conclusions: The lack of association with MS risk of the identified polymorphisms together with the transcription results discard chromosome 20 as genomic origin of MSRV-like env

Role of the Human Endogenous Retrovirus HERV-K18 in Autoimmune Disease Susceptibility: Study in the Spanish Population and Meta-Analysis

<div><p>Background</p><p>Human endogenous retroviruses (HERVs) are genomic sequences that resulted from ancestral germ-line infections by exogenous retroviruses and therefore are transmitted in a Mendelian fashion. Increased HERV expression and antibodies to HERV antigens have been found in various autoimmune diseases. HERV-K18 in chromosome 1 was previously associated with type one diabetes and multiple sclerosis (MS). The etiology of these complex conditions has not been completely elucidated even after the powerful genome wide association studies (GWAS) performed. Nonetheless, this approach does not scrutinize the repetitive sequences within the genome, and part of the missing heritability could lie behind these sequences. We aimed at evaluating the role of HERV-K18 in chromosome 1 on autoimmune disease susceptibility.</p><p>Methods</p><p>Two HERV-K18 SNPs (97Y/C and 154W/Stop substitutions) conforming three haplotypes were genotyped in Spanish cohorts of multiple sclerosis (n = 942), rheumatoid arthritis (n = 462) and ethnically matched controls (n = 601). Our findings were pooled in a meta-analysis including 5312 autoimmune patients and 4032 controls.</p><p>Results</p><p>Significant associations of both HERV-K18 polymorphisms in chromosome 1 with MS patients stratified by HLA-<i>DRB1*15∶01</i> were observed [97Y/C p = 0.02; OR (95% CI) = 1.5 (1.04–2.17) and 154W/Stop: p = 0.001; OR (95% CI) = 1.6 (1.19–2.16)]. Combined meta-analysis of the previously published association studies of HERV-K18 with different autoimmune diseases, together with data derived from Spanish cohorts, yielded a significant association of the HERV-K18.3 haplotype [97Y–154W: p_M-H = 0.0008; OR_M-H (95% CI) = 1.22 (1.09–1.38)].</p><p>Conclusion</p><p>Association of the HERV-K18.3 haplotype in chromosome 1 with autoimmune-disease susceptibility was confirmed through meta-analysis.</p></div

Evaluation Of The Cases With Intracranial Hypertension

Amaç: Düzce Üniversitesi Araştırma ve Uygulama Hastanesi, Nöroloji kliniğinde İHH tanısı konulmuş hastaların klinik bulgu ve tedavilerinin prognoz ile ilişkilerinin incelenmesi amaçlanmıştır. Gereç ve Yöntem: İİH tanısı ile tedavi ve takip edilen 23 hasta incelendi. Çalışmada Modifiye Dandy Kriterleri esas alındı. Kranial görüntüleme yapılarak, lomber ponksiyonları gerçekleştirildi. Bulgular: İİH tanılı hastaların %78,3'si kadın, %21,7 si erkekti. En sık başvuru nedeni olan baş ağrısına, bulanık görme, bakış kısıtlılığı, geçici görme kaybı, göz ağrısı, çift görme, bulantı, ışıktan rahatsız olma, baş dönmesi ve kulak çınlaması eşlik ediyordu. Hastaların %60.9'u obezdi. Beş hastada papil ödem gözlenmeksizin İİH tanısı saptandı.Empty sella dışında kranial görüntüleme normal sınırlardaydı. Tedavide, asetozolamid, metilprednisolon ve/veya topiramat verildi. Takip süresi 3-6 ay olarak düzenlendi. Bu süreç içinde görme kaybı yaşayan hastamız olmadı. Sonuç: Devamlılık gösteren atipik baş ağrı vakalarında, obezite varsa İİH tanısı düşünülerek ileri tetkik yapılmalıdır. Erken tedavi, olası görme kayıplarını önlemede önem taşımaktadır.Objective: In this study clinical findings of patients, who diagnosed with IIH in Duzce Univesity Research and Teaching Hospital Neurology Clinic were investigated. Materials and Methods: Treatment and follow-up of 23 patients were examined with diagnosis of IIH from the records. The study was based on modified Dandy criteria. The patients who were performed lumbar puncture and were done cranial imaging included in the study. Results: The patients diagnosed with IIH were 78.3% female and 21.7% male. The most common reason for admission was headache and it was accompanied by blurred vision, visual of limitation, temporary loss of vision, eye pain, double vision, nausea, dislike of light, dizziness and tinnitus. 60.9% of the patients were obese. Five patients without papilledema were diagnosed with IIH. The cranial imagings were in normal limits except for empty cella. In treatment, the patients were given acetozolamide, methylprednisolone and/or topiramate. The follow-up period was arranged in 3-6 months. In the process, there were not any patients who had loss of vision. Conclusion: Continuity in atypical cases of headache, if they have obesity, there should be further examination in mind of an IIH diagnosis. Early diagnosis and treatment are import to prevent the possible loss of vision

Strategy used for the selection of studies finally included in the meta-analysis.

<p>Strategy used for the selection of studies finally included in the meta-analysis.</p

HERV-W polymorphism in chromosome X is associated with multiple sclerosis risk and with differential expression of MSRV.

Journal Article; Research Support, Non-U.S. Gov't;BACKGROUND Multiple Sclerosis (MS) is an autoimmune demyelinating disease that occurs more frequently in women than in men. Multiple Sclerosis Associated Retrovirus (MSRV) is a member of HERV-W, a multicopy human endogenous retroviral family repeatedly implicated in MS pathogenesis. MSRV envelope protein is elevated in the serum of MS patients and induces inflammation and demyelination but, in spite of this pathogenic potential, its exact genomic origin and mechanism of generation are unknown. A possible link between the HERV-W copy on chromosome Xq22.3, that contains an almost complete open reading frame, and the gender differential prevalence in MS has been suggested. RESULTS MSRV transcription levels were higher in MS patients than in controls (U-Mann-Whitney; p = 0.004). Also, they were associated with the clinical forms (Spearman; p = 0.0003) and with the Multiple Sclerosis Severity Score (MSSS) (Spearman; p = 0.016). By mapping a 3 kb region in Xq22.3, including the HERV-W locus, we identified three polymorphisms: rs6622139 (T/C), rs6622140 (G/A) and rs1290413 (G/A). After genotyping 3127 individuals (1669 patients and 1458 controls) from two different Spanish cohorts, we found that in women rs6622139 T/C was associated with MS susceptibility: [χ2; p = 0.004; OR (95% CI) = 0.50 (0.31-0.81)] and severity, since CC women presented lower MSSS scores than CT (U-Mann-Whitney; p = 0.039) or TT patients (U-Mann-Whitney; p = 0.031). Concordantly with the susceptibility conferred in women, rs6622139*T was associated with higher MSRV expression (U-Mann-Whitney; p = 0.003). CONCLUSIONS Our present work supports the hypothesis of a direct involvement of HERV-W/MSRV in MS pathogenesis, identifying a genetic marker on chromosome X that could be one of the causes underlying the gender differences in MS.Instituto de Salud Carlos III-Fondo Investigaciones Sanitarias FIS (10/01985 and 09/02074), Fundación Genzyme, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, and Fundación LAIR.Ye

Role of HERV-K18 haplotypes A) Meta-analysis of case-control studies in different autoimmune disease cohorts; B) Spanish data stratified by HLA susceptibility alleles (<i>DRB1*15∶01</i> in MS and shared epitope in RA).

<p>Role of HERV-K18 haplotypes A) Meta-analysis of case-control studies in different autoimmune disease cohorts; B) Spanish data stratified by HLA susceptibility alleles (<i>DRB1*15∶01</i> in MS and shared epitope in RA).</p