Phylogenetic Analysis of Kindlins Suggests Subfunctionalization of an Ancestral Unduplicated Kindlin into Three Paralogs in Vertebrates

Kindlin proteins represent a newly discovered family of evolutionarily conserved FERM domain-containing proteins. This family includes three highly conserved proteins: Kindlin-1, Kindlin-2 and Kindlin-3. All three Kindlin proteins are associated with focal adhesions and are involved in integrin activation. The FERM domain of each Kindlin is bipartite and plays a key role in integrin activation. We herein explore for the first time the evolutionary history of these proteins. The phylogeny of the Kindlins suggests a single ancestral Kindlin protein present in even the earliest metazoan ie, hydra. This protein then underwent duplication events in insects and also experienced genome duplication in vertebrates, leading to the Kindlin family. A comparative study of the Kindlin paralogs showed that Kindlin-2 is the slowest evolving protein among the three family members. The analysis of synonymous and non-synonymous substitutions in orthologous Kindlin sequences in different species showed that all three Kindlins have been evolving under the influence of purifying selection. The expression pattern of Kindlins along with phylogenetic studies supports the subfunctionalization model of gene duplication

Vastus lateralis/vastus medialis cross-sectional area ratio impacts presence and degree of knee joint abnormalities and cartilage T2 determined with 3T MRI – an analysis from the incidence cohort of the Osteoarthritis Initiative

SummaryObjectiveTo study the role of vastus lateralis/vastus medialis cross-sectional area CSA ratio (VL/VM CSA ratio) in preclinical knee osteoarthritis (OA) using magnetic resonance imaging (MRI)-based cartilage T2 mapping technique and morphological analysis at 3.0T in non-symptomatic, middle-aged subjects.Material and methods174 non-symptomatic individuals aged 45–55 years with OA risk factors were selected from the Osteoarthritis Initiative (OAI) incidence cohort. OA-related knee abnormalities were analyzed using the whole-organ magnetic resonance imaging score (WORMS). Knee cartilage T2 maps were generated using sagittal 2D multi-echo spin-echo images of the right knee. CSA of thigh muscles was measured using axial T1W images of the right mid thigh. Spline-based segmentation of cartilage and muscles was performed on a SUN/SPARC workstation. Muscle measurements were normalized to body size using body surface area (BSA). Statistical significance was determined using Student’s t-test, Pearson correlation test, and multiple regression models. To correct for multiple testing, Bonferroni adjustments were applied across all tests within each of the primary results tables (Tables III–VII).ResultsHigher T2 values were associated with increased prevalence and severity of cartilage degeneration. In our study, male and female subjects with higher VL/VM CSA ratio demonstrated significantly lower mean cartilage T2 values (all compartments combined) (mean 44.10 vs 45.17, P=0.0017), and significantly lower WORMS scores (mean 14.12 vs 18.68, P=0.0316). Regression analyses of combined mean cartilage T2 using VL/VM CSA ratio as a continuous predictor showed a significant curvilinear relationship between these two variables (P=0.0082).ConclusionOur results suggested that higher VL/VM CSA ratio is associated with lower T2 values and decreased presence and severity of OA-related morphological changes. Additional studies will be needed to determine causality

A research pathway for experimental psychopathology: the role of external validity criteria

This paper outlines a putative pathway for experimental psychopathology research developing psychological models of clinical disorders. The pathway uses established external validity criteria to define the pathway and clarifies the important role that research conducted on healthy participants can play in our understanding of clinical disorders. Defining a research pathway for experimental psychopathology in this way has a number of benefits It would (1) make explicit the need to address the external validity of developed models, (2) provide a clear set of criteria that would be required to extend research on healthy individuals to diagnostic populations, and (3) recommend using general psychological knowledge when developing models of psychopathology

Two-Particle Correlation Functions for the 200-MeV 3-He + Ag Reaction

This research was sponsored by the National Science Foundation Grant NSF PHY-931478

Non-Thermal Behavior in Multifragment Decay

This research was sponsored by the National Science Foundation Grant NSF PHY-931478