Tapasin gene polymorphism in systemic onset juvenile rheumatoid arthritis: a family-based case-control study

Juvenile rheumatoid arthritis (JRA) comprises a group of chronic systemic inflammatory disorders that primarily affect joints and can cause long-term disability. JRA is likely to be a complex genetic trait, or a series of such traits, with both genetic and environmental factors contributing to the risk for developing the disease and to its progression. The HLA region on the short arm of chromosome 6 has been intensively evaluated for genetic contributors to JRA, and multiple associations, and more recently linkage, has been detected. Other genes involved in innate and acquired immunity also map to near the HLA cluster on 6p, and it is possible that variation within these genes also confers risk for developing JRA. We examined the TPSN gene, which encodes tapasin, an endoplasmic reticulum chaperone that is involved in antigen processing, to elucidate its involvement, if any, in JRA. We employed both a case-control approach and the transmission disequilibrium test, and found linkage and association between the TPSN allele (Arg260) and the systemic onset subtype of JRA. Two independent JRA cohorts were used, one recruited from the Rheumatology Clinic at Cincinnati Children's Hospital Medical Center (82 simplex families) and one collected by the British Paediatric Rheumatology Group in London, England (74 simplex families). The transmission disequilibrium test for these cohorts combined was statistically significant (chi(2) = 4.2, one degree of freedom; P = 0.04). Linkage disequilibrium testing between the HLA alleles that are known to be associated with systemic onset JRA did not reveal linkage disequilibrium with the Arg260 allele, either in the Cincinnati systemic onset JRA cohort or in 113 Caucasian healthy individuals. These results suggest that there is a weak association between systemic onset JRA and the TPSN polymorphism, possibly due to linkage disequilibrium with an as yet unknown susceptibility allele in the centromeric part of chromosome 6

Biological classification of childhood arthritis: roadmap to a molecular nomenclature

Chronic inflammatory arthritis in childhood is heterogeneous in presentation and course. Most forms exhibit clinical and genetic similarity to arthritis of adult onset, although at least one phenotype might be restricted to children. Nevertheless, paediatric and adult rheumatologists have historically addressed disease classification separately, yielding a juvenile idiopathic arthritis (JIA) nomenclature that exhibits no terminological overlap with adult-onset arthritis. Accumulating clinical, genetic and mechanistic data reveal the critical limitations of this strategy, necessitating a new approach to defining biological categories within JIA. In this Review, we provide an overview of the current evidence for biological subgroups of arthritis in children, delineate forms that seem contiguous with adult-onset arthritis, and consider integrative genetic and bioinformatic strategies to identify discrete entities within inflammatory arthritis across all ages

Anatomy and Taxonomic Status of the Chasmosaurine Ceratopsid Nedoceratops hatcheri from the Upper Cretaceous Lance Formation of Wyoming, U.S.A

Background: The validity of Nedoceratops hatcheri, a chasmosaurine ceratopsid dinosaur known from a single skull recovered in the Lance Formation of eastern Wyoming, U.S.A., has been debated for over a century. Some have argued that the taxon is an aberrant Triceratops, and most recently it was proposed that N. hatcheri represents an intermediate ontogenetic stage between ‘‘young adult’ ’ and ‘‘old adult’ ’ forms of a single taxon previously split into Triceratops and Torosaurus. Methodology/Principal Findings: The holotype skull of Nedoceratops hatcheri was reexamined in order to map reconstructed areas and compare the specimen with other ceratopsids. Although squamosal fenestrae are almost certainly not of taxonomic significance, some other features are unique to N. hatcheri. These include a nasal lacking a recognizable horn, nearly vertical postorbital horncores, and relatively small parietal fenestrae. Thus, N. hatcheri is tentatively considered valid, and closely related to Triceratops spp. The holotype of N. hatcheri probably represents an ‘‘old adult,’ ’ based upon bone surface texture and the shape of the horns and epiossifications on the frill. In this study, Torosaurus is maintained as a genus distinct from Triceratops and Nedoceratops. Synonymy of the three genera as ontogenetic stages of a single taxon would require cranial changes otherwise unknown in ceratopsids, including additions of ossifications to the frill and repeated alternation of bone surface texture between juvenile and adult morphotypes

Identification of Rice Transcription Factors Associated with Drought Tolerance Using the Ecotilling Method

The drought tolerance (DT) of plants is a complex quantitative trait. Under natural and artificial selection, drought tolerance represents the crop survival ability and production capacity under drought conditions (Luo, 2010). To understand the regulation mechanism of varied drought tolerance among rice genotypes, 95 diverse rice landraces or varieties were evaluated within a field screen facility based on the ‘line–source soil moisture gradient’, and their resistance varied from extremely resistant to sensitive. The method of Ecotype Targeting Induced Local Lesions in Genomes (Ecotilling) was used to analyze the diversity in the promoters of 24 transcription factor families. The bands separated by electrophoresis using Ecotilling were converted into molecular markers. STRUCTURE analysis revealed a value of K = 2, namely, the population with two subgroups (i.e., indica and japonica), which coincided very well with the UPGMA clusters (NTSYS-pc software) using distance-based analysis and InDel markers. Then the association analysis between the promoter diversity of these transcription factors and the DT index/level of each variety was performed. The results showed that three genes were associated with the DT index and that five genes were associated with the DT level. The sequences of these associated genes are complex and variable, especially at approximately 1000 bp upstream of the transcription initiation sites. The study illuminated that association analysis aimed at Ecotilling diversity of natural groups could facilitate the isolation of rice genes related to complex quantitative traits

Aetiology and risk factors of musculoskeletal disorders in physically active conscripts: a follow-up study in the Finnish Defence Forces

<p>Abstract</p> <p>Background</p> <p>Musculoskeletal disorders (MSDs) are the main reason for morbidity during military training. MSDs commonly result in functional impairment leading to premature discharge from military service and disabilities requiring long-term rehabilitation. The purpose of the study was to examine associations between various risk factors and MSDs with special attention to the physical fitness of the conscripts.</p> <p>Methods</p> <p>Two successive cohorts of 18 to 28-year-old male conscripts (<it>N </it>= 944, median age 19) were followed for six months. MSDs, including overuse and acute injuries, treated at the garrison clinic were identified and analysed. Associations between MSDs and risk factors were examined by multivariate Cox's proportional hazard models.</p> <p>Results</p> <p>During the six-month follow-up of two successive cohorts there were 1629 MSDs and 2879 health clinic visits due to MSDs in 944 persons. The event-based incidence rate for MSD was 10.5 (95% confidence interval (CI): 10.0-11.1) per 1000 person-days. Most MSDs were in the lower extremities (65%) followed by the back (18%). The strongest baseline factors associated with MSDs were poor result in the combined outcome of a 12-minute running test and back lift test (hazard ratio (HR) 2.9; 95% CI: 1.9-4.6), high waist circumference (HR 1.7; 95% CI: 1.3-2.2), high body mass index (HR 1.8; 95% CI: 1.3-2.4), poor result in a 12-minute running test (HR 1.6; 95% CI: 1.2-2.2), earlier musculoskeletal symptoms (HR 1.7; 95% CI: 1.3-2.1) and poor school success (educational level and grades combined; HR 2.0; 95% CI: 1.3-3.0). In addition, risk factors of long-term MSDs (≥10 service days lost due to one or several MSDs) were analysed: poor result in a 12-minute running test, earlier musculoskeletal symptoms, high waist circumference, high body mass index, not belonging to a sports club and poor result in the combined outcome of the 12-minute running test and standing long jump test were strongly associated with long-term MSDs.</p> <p>Conclusions</p> <p>The majority of the observed risk factors are modifiable and favourable for future interventions. An appropriate intervention based on the present study would improve both aerobic and muscular fitness prior to conscript training. Attention to appropriate waist circumference and body mass index would strengthen the intervention. Effective results from well-planned randomised controlled studies are needed before initiating large-scale prevention programmes in a military environment.</p

Human total, basal and activity energy expenditures are independent of ambient environmental temperature

Lower ambient temperature (Ta) requires greater energy expenditure to sustain body temperature. However, effects of Ta on human energetics may be buffered by environmental modification and behavioral compensation. We used the IAEA DLW database for adults in the USA (n = 3213) to determine the effect of Ta (−10 to +30°C) on TEE, basal (BEE) and activity energy expenditure (AEE) and physical activity level (PAL). There were no significant relationships (p > 0.05) between maximum, minimum and average Ta and TEE, BEE, AEE and PAL. After adjustment for fat-free mass, fat mass and age, statistically significant (p < 0.01) relationships between TEE, BEE and Ta emerged in females but the effect sizes were not biologically meaningful. Temperatures inside buildings are regulated at 18–25°C independent of latitude. Hence, adults in the US modify their environments to keep TEE constant across a wide range of external ambient temperatures

Injury rates and injury risk factors among federal bureau of investigation new agent trainees

<p>Abstract</p> <p>Background</p> <p>A one-year prospective examination of injury rates and injury risk factors was conducted in Federal Bureau of Investigation (FBI) new agent training.</p> <p>Methods</p> <p>Injury incidents were obtained from medical records and injury compensation forms. Potential injury risk factors were acquired from a lifestyle questionnaire and existing data at the FBI Academy.</p> <p>Results</p> <p>A total of 426 men and 105 women participated in the project. Thirty-five percent of men and 42% of women experienced one or more injuries during training. The injury incidence rate was 2.5 and 3.2 injuries/1,000 person-days for men and women, respectively (risk ratio (women/men) = 1.3, 95% confidence interval = 0.9-1.7). The activities most commonly associated with injuries (% of total) were defensive tactics training (58%), physical fitness training (20%), physical fitness testing (5%), and firearms training (3%). Among the men, higher injury risk was associated with older age, slower 300-meter sprint time, slower 1.5-mile run time, lower total points on the physical fitness test (PFT), lower self-rated physical activity, lower frequency of aerobic exercise, a prior upper or lower limb injury, and prior foot or knee pain that limited activity. Among the women higher injury risk was associated with slower 300-meter sprint time, slower 1.5-mile run time, lower total points on the PFT, and prior back pain that limited activity.</p> <p>Conclusion</p> <p>The results of this investigation supported those of a previous retrospective investigation emphasizing that lower fitness and self-reported pain limiting activity were associated with higher injury risk among FBI new agents.</p

New Information on the Cranial Anatomy of Acrocanthosaurus atokensis and Its Implications for the Phylogeny of Allosauroidea (Dinosauria: Theropoda)

Allosauroidea has a contentious taxonomic and systematic history. Within this group of theropod dinosaurs, considerable debate has surrounded the phylogenetic position of the large-bodied allosauroid Acrocanthosaurus atokensis from the Lower Cretaceous Antlers Formation of North America. Several prior analyses recover Acrocanthosaurus atokensis as sister taxon to the smaller-bodied Allosaurus fragilis known from North America and Europe, and others nest Acrocanthosaurus atokensis within Carcharodontosauridae, a large-bodied group of allosauroids that attained a cosmopolitan distribution during the Early Cretaceous.Re-evaluation of a well-preserved skull of Acrocanthosaurus atokensis (NCSM 14345) provides new information regarding the palatal complex and inner surfaces of the skull and mandible. Previously inaccessible internal views and articular surfaces of nearly every element of the skull are described. Twenty-four new morphological characters are identified as variable in Allosauroidea, combined with 153 previously published characters, and evaluated for eighteen terminal taxa. Systematic analysis of this dataset recovers a single most parsimonious topology placing Acrocanthosaurus atokensis as a member of Allosauroidea, in agreement with several recent analyses that nest the taxon well within Carcharodontosauridae.A revised diagnosis of Acrocanthosaurus atokensis finds that the species is distinguished by four primary characters, including: presence of a knob on the lateral surangular shelf; enlarged posterior surangular foramen; supraoccipital protruding as a double-boss posterior to the nuchal crest; and pneumatic recess within the medial surface of the quadrate. Furthermore, the recovered phylogeny more closely agrees with the stratigraphic record than hypotheses that place Acrocanthosaurus atokensis as more closely related to Allosaurus fragilis. Fitch optimization of body size is also more consistent with the placement of Acrocanthosaurus atokensis within a clade of larger carcharodontosaurid taxa than with smaller-bodied taxa near the base of Allosauroidea. This placement of Acrocanthosaurus atokensis supports previous hypotheses of a global carcharodontosaurid radiation during the Early Cretaceous

A basal lithostrotian titanosaur (Dinosauria: Sauropoda) with a complete skull: Implications for the evolution and paleobiology of titanosauria

We describe Sarmientosaurus musacchioi gen. et sp. nov., a titanosaurian sauropod dinosaur from the Upper Cretaceous (Cenomanian - Turonian) Lower Member of the Bajo Barreal Formation of southern Chubut Province in central Patagonia, Argentina. The holotypic and only known specimen consists of an articulated, virtually complete skull and part of the cranial and middle cervical series. Sarmientosaurus exhibits the following distinctive features that we interpret as autapomorphies: (1) maximum diameter of orbit nearly 40% rostrocaudal length of cranium; (2) complex maxilla - lacrimal articulation, in which the lacrimal clasps the ascending ramus of the maxilla; (3) medial edge of caudal sector of maxillary ascending ramus bordering bony nasal aperture with low but distinct ridge; (4) ´tongue-like´ ventral process of quadratojugal that overlaps quadrate caudally; (5) separate foramina for all three branches of the trigeminal nerve; (6) absence of median venous canal connecting infundibular region to ventral part of brainstem; (7) subvertical premaxillary, procumbent maxillary, and recumbent dentary teeth; (8) cervical vertebrae with ´strut-like´ centroprezygapophyseal laminae; (9) extremely elongate and slender ossified tendon positioned ventrolateral to cervical vertebrae and ribs. The cranial endocast of Sarmientosaurus preserves some of the most complete information obtained to date regarding the brain and sensory systems of sauropods. Phylogenetic analysis recovers the new taxon as a basal member of Lithostrotia, as the most plesiomorphic titanosaurian to be preserved with a complete skull. Sarmientosaurus provides a wealth of new cranial evidence that reaffirms the close relationship of titanosaurs to Brachiosauridae. Moreover, the presence of the relatively derived lithostrotian Tapuiasaurus in Aptian deposits indicates that the new Patagonian genus represents a ´ghost lineage´ with a comparatively plesiomorphic craniodental form, the evolutionary history of which is missing for at least 13 million years of the Cretaceous. The skull anatomy of Sarmientosaurus suggests that multiple titanosaurian species with dissimilar cranial structures coexisted in the early Late Cretaceous of southern South America. Furthermore, the new taxon possesses a number of distinctive morphologies - such as the ossified cervical tendon, extremely pneumatized cervical vertebrae, and a habitually downward- facing snout - that have rarely, if ever, been documented in other titanosaurs, thus broadening our understanding of the anatomical diversity of this remarkable sauropod clade. The latter two features were convergently acquired by at least one penecontemporaneous diplodocoid, and may represent mutual specializations for consuming low-growing vegetation.Fil: Martínez, Rubén Darío. Universidad Nacional de la Patagonia; ArgentinaFil: Lamanna, Matthew C.. Carnegie Museum Of Natural History; Estados UnidosFil: Novas, Fernando Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "bernardino Rivadavia"; ArgentinaFil: Ridgely, Ryan C.. Ohio University College Of Osteopathic Medicine; Estados UnidosFil: Casal, Gabriel. Universidad Nacional de la Patagonia; ArgentinaFil: Martínez, Javier E.. Hospital Regional de Comodoro Rivadavia; ArgentinaFil: Vita, Javier R.. Resonancia Magnética Borelli; ArgentinaFil: Witmer, Lawrence M.. Ohio University College Of Osteopathic Medicine; Estados Unido

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field