Rotational strength, range of motion, and function in people with unaffected shoulders from various stages of life

Background: Different measurements are used to assess shoulder function, including range of motion, strength, functional performance and self-report function. To understand disablement, it is necessary to understand the relationship between impairments and function in persons without shoulder problems. This study was conducted to enhance existing comparative data in subjects without upper extremity pathology, and to assess the relationships between impairments (range of motion, strength) and selfreported or measured function/disability. The impact of age, gender and dominance was determined. Methods: Two-hundred ninety-four subjects with unaffected shoulders were recruited. The subjects (mean age: 37 years old) were divided into three subgroups, 18–39, 40–59, and over 60 years of age. During a single session, at least two of the following variables were measured: self-reported function (shoulder disability scales), range of motion, isometric rotational strength, or upper limb functional performance (FIT-HaNSA). Two-way analysis of variance was used to determine, for each variable, the effects of age and gender. The relationship between the outcomes was established using Pearson product correlations. Results: Men were significantly stronger than women for all age categories. There was an age-related decline in strength in men in the over-60 age category. Significant negative correlations between strength and range of motion were demonstrated (-0.22 \u3c -0.32). Women had a significantly higher range of motion than men for external rotation in the 40–59 age category. Furthermore, the subjects in the over- 60 age category experienced a decrease of range of motion. There was minimal disability reported in all age groups on self-report scales. Only the Simple Shoulder Test demonstrated significant decreases in the over-60 age category and correlated with age (r = -0.202). Conclusion: Self-reported disability was low in individuals without upper extremity problems, although recruitment of such individuals was difficult in the older age groups due to the high prevalence of shoulder pathology. A low correlation between self-report disability and strength/range of motion in these unaffected subjects reflects the lack of disability reported by all subjects without pathology despite normal variations in strength and motion

Structural Insights into the Evolution of a Non-Biological Protein: Importance of Surface Residues in Protein Fold Optimization

Phylogenetic profiling of amino acid substitution patterns in proteins has led many to conclude that most structural information is carried by interior core residues that are solvent inaccessible. This conclusion is based on the observation that buried residues generally tolerate only conserved sequence changes, while surface residues allow more diverse chemical substitutions. This notion is now changing as it has become apparent that both core and surface residues play important roles in protein folding and stability. Unfortunately, the ability to identify specific mutations that will lead to enhanced stability remains a challenging problem. Here we discuss two mutations that emerged from an in vitro selection experiment designed to improve the folding stability of a non-biological ATP binding protein. These mutations alter two solvent accessible residues, and dramatically enhance the expression, solubility, thermal stability, and ligand binding affinity of the protein. The significance of both mutations was investigated individually and together, and the X-ray crystal structures of the parent sequence and double mutant protein were solved to a resolution limit of 2.8 and 1.65 Å, respectively. Comparative structural analysis of the evolved protein to proteins found in nature reveals that our non-biological protein evolved certain structural features shared by many thermophilic proteins. This experimental result suggests that protein fold optimization by in vitro selection offers a viable approach to generating stable variants of many naturally occurring proteins whose structures and functions are otherwise difficult to study

A Linear Framework for Time-Scale Separation in Nonlinear Biochemical Systems

Cellular physiology is implemented by formidably complex biochemical systems with highly nonlinear dynamics, presenting a challenge for both experiment and theory. Time-scale separation has been one of the few theoretical methods for distilling general principles from such complexity. It has provided essential insights in areas such as enzyme kinetics, allosteric enzymes, G-protein coupled receptors, ion channels, gene regulation and post-translational modification. In each case, internal molecular complexity has been eliminated, leading to rational algebraic expressions among the remaining components. This has yielded familiar formulas such as those of Michaelis-Menten in enzyme kinetics, Monod-Wyman-Changeux in allostery and Ackers-Johnson-Shea in gene regulation. Here we show that these calculations are all instances of a single graph-theoretic framework. Despite the biochemical nonlinearity to which it is applied, this framework is entirely linear, yet requires no approximation. We show that elimination of internal complexity is feasible when the relevant graph is strongly connected. The framework provides a new methodology with the potential to subdue combinatorial explosion at the molecular level

Noise Contributions in an Inducible Genetic Switch: A Whole-Cell Simulation Study

Stochastic expression of genes produces heterogeneity in clonal populations of bacteria under identical conditions. We analyze and compare the behavior of the inducible lac genetic switch using well-stirred and spatially resolved simulations for Escherichia coli cells modeled under fast and slow-growth conditions. Our new kinetic model describing the switching of the lac operon from one phenotype to the other incorporates parameters obtained from recently published in vivo single-molecule fluorescence experiments along with in vitro rate constants. For the well-stirred system, investigation of the intrinsic noise in the circuit as a function of the inducer concentration and in the presence/absence of the feedback mechanism reveals that the noise peaks near the switching threshold. Applying maximum likelihood estimation, we show that the analytic two-state model of gene expression can be used to extract stochastic rates from the simulation data. The simulations also provide mRNA–protein probability landscapes, which demonstrate that switching is the result of crossing both mRNA and protein thresholds. Using cryoelectron tomography of an E. coli cell and data from proteomics studies, we construct spatial in vivo models of cells and quantify the noise contributions and effects on repressor rebinding due to cell structure and crowding in the cytoplasm. Compared to systems without spatial heterogeneity, the model for the fast-growth cells predicts a slight decrease in the overall noise and an increase in the repressors rebinding rate due to anomalous subdiffusion. The tomograms for E. coli grown under slow-growth conditions identify the positions of the ribosomes and the condensed nucleoid. The smaller slow-growth cells have increased mRNA localization and a larger internal inducer concentration, leading to a significant decrease in the lifetime of the repressor–operator complex and an increase in the frequency of transcriptional bursts

Carpal Tunnel Syndrome: A Review of the Recent Literature

Carpal Tunnel Syndrome (CTS) remains a puzzling and disabling condition present in 3.8% of the general population. CTS is the most well-known and frequent form of median nerve entrapment, and accounts for 90% of all entrapment neuropathies. This review aims to provide an overview of this common condition, with an emphasis on the pathophysiology involved in CTS. The clinical presentation and risk factors associated with CTS are discussed in this paper. Also, the various methods of diagnosis are explored; including nerve conduction studies, ultrasound, and magnetic resonance imaging

The Rodin-Ohno hypothesis that two enzyme superfamilies descended from one ancestral gene: an unlikely scenario for the origins of translation that will not be dismissed

Background Because amino acid activation is rate-limiting for uncatalyzed protein synthesis, it is a key puzzle in understanding the origin of the genetic code. Two unrelated classes (I and II) of contemporary aminoacyl-tRNA synthetases (aaRS) now translate the code. Observing that codons for the most highly conserved, Class I catalytic peptides, when read in the reverse direction, are very nearly anticodons for Class II defining catalytic peptides, Rodin and Ohno proposed that the two superfamilies descended from opposite strands of the same ancestral gene. This unusual hypothesis languished for a decade, perhaps because it appeared to be unfalsifiable. Results The proposed sense/antisense alignment makes important predictions. Fragments that align in antiparallel orientations, and contain the respective active sites, should catalyze the same two reactions catalyzed by contemporary synthetases. Recent experiments confirmed that prediction. Invariant cores from both classes, called Urzymes after Ur = primitive, authentic, plus enzyme and representing ~20% of the contemporary structures, can be expressed and exhibit high, proportionate rate accelerations for both amino-acid activation and tRNA acylation. A major fraction (60%) of the catalytic rate acceleration by contemporary synthetases resides in segments that align sense/antisense. Bioinformatic evidence for sense/antisense ancestry extends to codons specifying the invariant secondary and tertiary structures outside the active sites of the two synthetase classes. Peptides from a designed, 46-residue gene constrained by Rosetta to encode Class I and II ATP binding sites with fully complementary sequences both accelerate amino acid activation by ATP ~400 fold. Conclusions Biochemical and bioinformatic results substantially enhance the posterior probability that ancestors of the two synthetase classes arose from opposite strands of the same ancestral gene. The remarkable acceleration by short peptides of the rate-limiting step in uncatalyzed protein synthesis, together with the synergy of synthetase Urzymes and their cognate tRNAs, introduce a new paradigm for the origin of protein catalysts, emphasize the potential relevance of an operational RNA code embedded in the tRNA acceptor stems, and challenge the RNA-World hypothesis. Reviewers This article was reviewed by Dr. Paul Schimmel (nominated by Laura Landweber), Dr. Eugene Koonin and Professor David Ardell

Wrist and palm indexes in carpal tunnel syndrome Índices de palma/punho e síndrome do túnel do carpo

According to median sensory latency > or = 3.7 ms (wrist-index finger [WIF], 14 cm), median/ulnar sensory latency difference to ring finger > or = 0.5 ms (14 cm) or median midpalm (8 cm) latency > or = 2.3 ms (all peak-measured), 141 Brazilian symptomatic patients (238 hands) have CTS confirmation. Wrist ratio (depth divided by width, WR) and a new wrist/palm ratio (wrist depth divided by the distance between distal wrist crease to the third digit metacarpophalangeal crease, WPR) were measured in all cases. Previous surgery/peripheral neuropathy were excluded; mean age 50.3 years; 90.8% female. Control subjects (486 hands) have mean age 43.0 years; 96.7% female. The mean WR in controls was 0.694 against 0.699, 0.703, 0.707 and 0.721 in CTS groups of progressive WIF severity. The mean WPR in controls was 0.374 against 0.376, 0.382, 0.387 and 0.403 in CTS groups of WIF progressive severity. Both were statistically significant for the last two groups (WIF > 4.4 ms, moderate, and, WIF unrecordable, severe). BMI increases togetherwith CTS severity and WR. It was concluded that both WR/WPR have a progressive correlation with the severity of CTS but with statistically significance only in groups moderate and severe. In these groups both WR and BMI have progressive increase and we believe that the latter could be a risk factor as important as important WR/WPR.<br>Um grupo de 141 pacientes (238 mãos) com síndrome do túnel do carpo (STC) sintomático foi estudado após confirmação por condução nervosa: latência distal sensitiva do nervo mediano (LDS-M) > ou = 3,7 ms (punho -- II dedo, 14 cm), diferença de latência sensitiva mediano-ulnar > ou = 0,5 ms (punho -- IV dedo, 14 cm) e/ou latência palma-punho do nervo mediano > ou = 2,3 ms (8 cm); as latências foram medidas no pico do potencial. Todos os casos tiveram as seguintes medidas calculadas: 1. Índice do punho (IP, espessura dividido pela largura do punho); 2. Índice punho-palma (IPP, espessura do punho dividido pela distância entre a prega distal do punho e a prega mais proximal do III dedo); a média de idade foi de 50,3 anos com 90,8% do gênero feminino. Foram realizadas mesmas medidas em 486 mãos do grupo controle (GC) cuja idade média foi 43,0 anos e 96,7% do gênero feminino. O IP médio do GC foi de 0,694 contra 0,699/0,703/0,707/0,721 do grupo STC (valores relativos a casos incipiente/leve/moderado/grave). O IPP médio do GC foi de 0,374 contra 0,376/0,382/0,387/0,403 do grupo STC. Ambos os índices apresentaram significância estatística na comparação com STC mais grave (moderado: LDS-M > 4,4 ms e grave: LDS-M não obtida). O índice de massa corporal aumentou de acordo com a gravidade do STC e o IP. Conclui-se que tanto o IP como o IPP apresentam correlação progressiva com a gravidade do STC porém com significância estatística apenas nos grupos moderado e grave. Neste grupos tanto o IP como o índice de massa corporal tiveram aumento progressivo e acreditamos que o último possa representar risco tão importante quanto IP/IPP