Paleobiology of titanosaurs: reproduction, development, histology, pneumaticity, locomotion and neuroanatomy from the South American fossil record

Fil: García, Rodolfo A.. Instituto de Investigación en Paleobiología y Geología. Museo Provincial Carlos Ameghino. Cipolletti; ArgentinaFil: Salgado, Leonardo. Instituto de Investigación en Paleobiología y Geología. General Roca. Río Negro; ArgentinaFil: Fernández, Mariela. Inibioma-Centro Regional Universitario Bariloche. Bariloche. Río Negro; ArgentinaFil: Cerda, Ignacio A.. Instituto de Investigación en Paleobiología y Geología. Museo Provincial Carlos Ameghino. Cipolletti; ArgentinaFil: Carabajal, Ariana Paulina. Museo Carmen Funes. Plaza Huincul. Neuquén; ArgentinaFil: Otero, Alejandro. Museo de La Plata. Universidad Nacional de La Plata; ArgentinaFil: Coria, Rodolfo A.. Instituto de Paleobiología y Geología. Universidad Nacional de Río Negro. Neuquén; ArgentinaFil: Fiorelli, Lucas E.. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica. Anillaco. La Rioja; Argentin

Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus

Objective: Systemic lupus erythematosus is a clinically heterogeneous autoimmune disease. A number of genetic loci that increase lupus susceptibility have been established. This study examines if these genetic loci also contribute to the clinical heterogeneity in lupus. Materials and methods: 4001 European-derived, 547 Hispanic, 1590 African-American and 1191 Asian lupus patients were genotyped for 16 confirmed lupus susceptibility loci. Ancestry informative markers were genotyped to calculate and adjust for admixture. The association between the risk allele in each locus was determined and compared in patients with and without the various clinical manifestations included in the ACR criteria. Results: Renal disorder was significantly correlated with the lupus risk allele in ITGAM (p=5.0 × 10-6, OR 1.25, 95% CI 1.12 to 1.35) and in TNFSF4 (p=0.0013, OR 1.14, 95% CI 1.07 to 1.25). Other significant findings include the association between risk alleles in FCGR2A and malar rash (p=0.0031, OR 1.11, 95% CI 1.17 to 1.33), ITGAM and discoid rash (p=0.0020, OR 1.20, 95% CI 1.06 to 1.33), STAT4 and protection from oral ulcers (p=0.0027, OR 0.89, 95% CI 0.83 to 0.96) and IL21 and haematological disorder (p=0.0027, OR 1.13, 95% CI 1.04 to 1.22). All these associations are significant with a false discovery rate of and lt;0.05 and pass the significance threshold using Bonferroni correction for multiple testing. Conclusion: Significant associations were found between lupus clinical manifestations and the FCGR2A, ITGAM, STAT4, TNSF4 and IL21 genes. The findings suggest that genetic profiling might be a useful tool to predict disease manifestations in lupus patients in the future

Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus

Objective: Systemic lupus erythematosus is a clinically heterogeneous autoimmune disease. A number of genetic loci that increase lupus susceptibility have been established. This study examines if these genetic loci also contribute to the clinical heterogeneity in lupus. Materials and methods: 4001 European-derived, 547 Hispanic, 1590 African-American and 1191 Asian lupus patients were genotyped for 16 confirmed lupus susceptibility loci. Ancestry informative markers were genotyped to calculate and adjust for admixture. The association between the risk allele in each locus was determined and compared in patients with and without the various clinical manifestations included in the ACR criteria. Results: Renal disorder was significantly correlated with the lupus risk allele in ITGAM (p=5.0 × 10-6, OR 1.25, 95% CI 1.12 to 1.35) and in TNFSF4 (p=0.0013, OR 1.14, 95% CI 1.07 to 1.25). Other significant findings include the association between risk alleles in FCGR2A and malar rash (p=0.0031, OR 1.11, 95% CI 1.17 to 1.33), ITGAM and discoid rash (p=0.0020, OR 1.20, 95% CI 1.06 to 1.33), STAT4 and protection from oral ulcers (p=0.0027, OR 0.89, 95% CI 0.83 to 0.96) and IL21 and haematological disorder (p=0.0027, OR 1.13, 95% CI 1.04 to 1.22). All these associations are significant with a false discovery rate of and lt;0.05 and pass the significance threshold using Bonferroni correction for multiple testing. Conclusion: Significant associations were found between lupus clinical manifestations and the FCGR2A, ITGAM, STAT4, TNSF4 and IL21 genes. The findings suggest that genetic profiling might be a useful tool to predict disease manifestations in lupus patients in the future

Association of PPP2CA polymorphisms with systemic lupus erythematosus susceptibility in multiple ethnic groups

Objective T cells from patients with systemic lupus erythematosus (SLE) express increased amounts of PP2Ac, which contributes to decreased production of interleukin-2 (IL-2). Because IL-2 is important in the regulation of several aspects of the immune response, it has been proposed that PP2Ac contributes to the expression of SLE. This study was designed to determine whether genetic variants of PPP2AC are linked to the expression of SLE and specific clinical manifestations and account for the increased expression of PP2Ac. Methods We conducted a trans-ethnic study of 8,695 SLE cases and 7,308 controls of 4 different ancestries. Eighteen single-nucleotide polymorphisms (SNPs) across PPP2CA were genotyped using an Illumina custom array. PPP2CA expression in SLE and control T cells was analyzed by real-time polymerase chain reaction. Results A 32-kb haplotype comprising multiple SNPs of PPP2CA showed significant association with SLE in Hispanic Americans, European Americans, and Asians, but not in African Americans. Conditional analyses revealed that SNP rs7704116 in intron 1 showed consistently strong association with SLE across Asian, European American, and Hispanic American populations (odds ratio 1.3 [95% confidence interval 1.14-1.31], meta-analysis P = 3.8 × 10 -7). In European Americans, the largest ethnic data set studied, the risk A allele of rs7704116 was associated with the presence of renal disease, anti-double-stranded DNA, and anti-RNP antibodies. PPP2CA expression was ?2-fold higher in SLE patients carrying the rs7704116 AG genotype than those carrying the GG genotype (P = 0.007). Conclusion Our data provide the first evidence of an association between PPP2CA polymorphisms and elevated PP2Ac transcript levels in T cells, which implicates a new molecular pathway for SLE susceptibility in European Americans, Hispanic Americans, and Asians. Copyright © 2011 by the American College of Rheumatology

Association of PPP2CA polymorphisms with systemic lupus erythematosus susceptibility in multiple ethnic groups

Objective T cells from patients with systemic lupus erythematosus (SLE) express increased amounts of PP2Ac, which contributes to decreased production of interleukin-2 (IL-2). Because IL-2 is important in the regulation of several aspects of the immune response, it has been proposed that PP2Ac contributes to the expression of SLE. This study was designed to determine whether genetic variants of PPP2AC are linked to the expression of SLE and specific clinical manifestations and account for the increased expression of PP2Ac. Methods We conducted a trans-ethnic study of 8,695 SLE cases and 7,308 controls of 4 different ancestries. Eighteen single-nucleotide polymorphisms (SNPs) across PPP2CA were genotyped using an Illumina custom array. PPP2CA expression in SLE and control T cells was analyzed by real-time polymerase chain reaction. Results A 32-kb haplotype comprising multiple SNPs of PPP2CA showed significant association with SLE in Hispanic Americans, European Americans, and Asians, but not in African Americans. Conditional analyses revealed that SNP rs7704116 in intron 1 showed consistently strong association with SLE across Asian, European American, and Hispanic American populations (odds ratio 1.3 [95% confidence interval 1.14-1.31], meta-analysis P = 3.8 × 10 -7). In European Americans, the largest ethnic data set studied, the risk A allele of rs7704116 was associated with the presence of renal disease, anti-double-stranded DNA, and anti-RNP antibodies. PPP2CA expression was ?2-fold higher in SLE patients carrying the rs7704116 AG genotype than those carrying the GG genotype (P = 0.007). Conclusion Our data provide the first evidence of an association between PPP2CA polymorphisms and elevated PP2Ac transcript levels in T cells, which implicates a new molecular pathway for SLE susceptibility in European Americans, Hispanic Americans, and Asians. Copyright © 2011 by the American College of Rheumatology

Paleobiología de Titanosaurios de Sudamérica: reproducción, desarrollo, histología, neumaticidad, locomoción y neuroanatomía

Much of the current paleobiological knowledge on titanosaur sauropods was attained in just the last fifteen years, in particular that related to reproductive and developmental biology. Recent years have also seen progress on other poorly explored topics, such as pneumaticity, muscle architecture and locomotion, and endocast reconstruction and associated structures. Some titanosaurs laid numerous, relatively small Megaloolithidae eggs (with diameters ranging from 12 to 14 cm) in nests dug In the ground and, as known from the South American records, probably eggs of the multispherulitic morphotype. During ontogeny, certain titanosaurs displayed some variations in cranial morphology, some of them likely associated with the differing feeding habits between hatchlings and adults. The bone tissue of some adult titanosaurs was rapidly and cyclically deposited and shows a greater degree of remodeling than in other sauropods. Saltasaurines in particular show evidence of postcranial skeletal pneumaticity in both axial and appendicular skeleton, providing clues about soft tissue anatomy and the structure of the respiratory system. Titanosaurs, like all sauropods, were characterized by being fully quadrupedal, although some appendicular features and putative trackways indicate that their stance was not as columnar as in other sauropods. These anatomical peculiarities are significantly developed In saltasaurines, a derived group of titanosaurs. Compared with other sauropods, some titanosaurs seem to have had very poor olfaction but would have been capable of capturing sounds In a relatively wide range of high frequencies, although not to the extent of living birds.El conocimiento paleobiológico de los saurópodos titanosaurios, particularmente su reproducción y biología del desarrollo, fue alcanzado recién en los últimos quince años. En estos últimos años también se ha avanzado en temas poco explorados hasta el momento, como la neumatización, su arquitectura muscular y locomoción y la reconstrucción de partes blandas como el cerebro y estructuras asociadas. Algunos titanosaurios depositan sus numerosos y pequeños huevos megaloolitidos en nidos excavados sobre el suelo. Durante la ontogenia ciertos titanosaurios exponen algunas variaciones en su morfología craneana, algunas de estas probablemente asociadas con las diferentes maneras de alimentarse que tendrían los juveniles y los adultos. El tejido óseo de algunos titanosaurios adultos se habría depositado rápido y cíclicamente, exponiendo una mayor remodelación que en otros saurópodos. Los titanosaurios, particularmente los saltasaurinos, exponen una neumaticidad postcraneal en el esqueleto axial y apendicular, este carácter permite Inferir la anatomía de sus tejidos blandos y de su sistema respiratorio. Los titanosaurios, como todos los saurópodos, estaban caracterizados por ser cuadrúpedos, aunque algunos caracteres apendiculares y las huellas indican que su postura no habría sido tan columnar como en otros saurópodos. Aquellas peculiaridades anatómicas están notoriamente desarrolladas en los saltasaurinos, un grupo de titanosaurios derivados. Comparado con otros saurópodos, algunos titanosaurios parecen haber tenido un pobre sentido del olfato, sin embargo estos habrían tenido la capacidad de captar sonidos de alta frecuencia en un rango relativamente amplio, aunque no tanto como las aves actuales.Fil: Garcia, Rodolfo Andres. Provincia de Río Negro. Museo Provincial “Carlos Ameghino”. Instituto de Investigación en Paleobiología y Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Salgado, Leonardo. Provincia de Río Negro. Instituto de Investigación en Paleobiología y Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fernández, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Patagonia Norte. Instituto de Investigación en Biodiversidad y Medioambiente; Argentina. Universidad Nacional del Comahue. Centro Regional Universitario Bariloche; ArgentinaFil: Cerda, Ignacio Alejandro. Provincia de Río Negro. Museo Provincial “Carlos Ameghino”. Instituto de Investigación en Paleobiología y Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paulina Carabajal, Ariana. Provincia del Neuquen. Municipalidad de Plaza Huincul. Museo "Carmen Funes"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Otero, Alejandro. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Departamento Científico de Paleontología de Vertebrados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Coria, Rodolfo Anibal. Universidad Nacional de Rio Negro. Sede Alto Valle. Instituto de Investigaciones en Paleobiologia y Geologia; Argentina. Provincia del Neuquen. Municipalidad de Plaza Huincul. Museo "Carmen Funes"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fiorelli, Lucas Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Regional de Investigaciones Cientificas y Transferencia Tecnológica de Anillaco; Argentin