Osteotomy of the greater trochanter: effect on gluteus medius function

PURPOSE Advancement of the greater trochanter alters the function of the gluteus medius muscle. However, with the exception of clinical studies and biomechanical lever arm studies, no publications that analyze the consequences of advancement of the greater trochanter on the muscle function exist. The aim of the study was to analyze the mechanical changes of gluteus medius after osteotomy of the greater trochanter in a lab setting. METHODS An anatomical study of origin and insertion of the gluteus medius was carried out on four hips. Based on the dissections, a string model was developed dividing the muscle into five sectors. Changes in muscle fiber length were measured for every 10° of flexion, internal and external rotation and abduction with the trochanter in anatomic, proximalized and distalized positions. RESULTS Distalization of the trochanter leads to an imbalance of muscle action, moving the isometric sector of the muscle anteriorly with more muscle sectors being active during flexion and less during extension. Stretching of the muscle increases passive forces but decreases the force generation capacity of the muscle and at the same time increased muscle fiber excursion may require more energy consumption, which may explain earlier fatigue of the abductor musculature after distalization of the trochanter. For abduction, distalization of the muscle attachment leads to a change in contraction pattern from isometric to isotonic. Optimal balancing and excursion of the muscle is when the tip of the greater trochanter is at level with the hip rotation center. CONCLUSIONS In hips with high riding trochanter, the optimal position is at the level of the center of hip rotation. Excessive distalization should be avoided. As the conclusions and considerations are based on a lab setting, transfer to clinical practice may not necessarily apply.

An extracytoplasmic function sigma factor operon regulates Myxococcus xanthus developmental gene expression

Myxococcus xanthus is a Gram-negative soil bacterium that undergoes multicellular development when high-density cells are starved on a solid surface. Expression of the 4445 gene, predicted to encode a periplasmic protein, commences 1.5 h after the initiation of development and requires starvation and high density conditions. Addition of crude or boiled supernatant from starving high-density cells restored 4445 expression to starving low-density cells. Addition of L-threonine or L-isoleucine to starving low-density cells also restored 4445 expression, indicating that the high-density signaling activity present in the supernatant might be composed of extracellular amino acids or small peptides. To investigate the circuitry integrating these starvation and high-density signals, the cis- and trans-acting elements controlling 4445 expression were identified. The 4445 transcription start site was determined by primer extension analysis to be 58 by upstream of the predicted translation start site. The promoter region contained a consensus sequence characteristic of e&barbelow;xtrac&barbelow;ytoplasmic f&barbelow;unction (ECF) sigma factor-dependent promoters, suggesting that 4445 expression might be regulated by an ECF sigma factor-dependent pathway, which are known to respond to envelope stresses. The small size of the minimum regulatory region, identified by 5′-end deletion analysis as being only 66 by upstream of the transcription start site, suggests that RNA polymerase could be the sole direct regulator of 4445 expression. To identify trans-acting negative regulators of 4445 expression, a strain containing a 4445-lacZ was mutagenized using the Himar1-tet transposon. The four transposon insertions characterized mapped to an operon encoding a putative ECF sigma factor, ecfA; an anti-sigma factor, reaA; and a negative regulator, reaB. The reaA and the reaB mutants expressed 4445 during growth and development at levels almost 100-fold higher than wild type, indicating that these genes encode negative regulators. The ecfA mutant expressed 4445-lacZ at basal levels, indicating that ecfA is a positive regulator. High Mg2+ concentrations over-stimulated this ecfA pathway possibly due to the depletion of exopolysaccharides and assembled type IV pili. These data indicate that the ecfA operon encodes a new regulatory stress pathway that integrates and transduces starvation and cell density cues during early development and is also responsive to cell-surface alterations.^

Age -period -cohort analysis: An extension of Cox's lifetable regression with time -dependent covariates

It is well known that an identification problem exists in the analysis of age-period-cohort data because of the relationship among the three factors (date of birth + age at death = date of death). There are numerous suggestions about how to analyze the data. No one solution has been satisfactory. The purpose of this study is to provide another analytic method by extending the Cox's lifetable regression model with time-dependent covariates. The new approach contains the following features: (1) It is based on the conditional maximum likelihood procedure using a proportional hazard function described by Cox (1972), treating the age factor as the underlying hazard to estimate the parameters for the cohort and period factors. (2) The model is flexible so that both the cohort and period factors can be treated as dummy or continuous variables, and the parameter estimations can be obtained for numerous combinations of variables as in a regression analysis. (3) The model is applicable even when the time period is unequally spaced.^ Two specific models are considered to illustrate the new approach and applied to the U.S. prostate cancer data. We find that there are significant differences between all cohorts and there is a significant period effect for both whites and nonwhites. The underlying hazard increases exponentially with age indicating that old people have much higher risk than young people. A log transformation of relative risk shows that the prostate cancer risk declined in recent cohorts for both models. However, prostate cancer risk declined 5 cohorts (25 years) earlier for whites than for nonwhites under the period factor model (0 0 0 1 1 1 1). These latter results are similar to the previous study by Holford (1983).^ The new approach offers a general method to analyze the age-period-cohort data without using any arbitrary constraint in the model. ^

Seawater carbonate chemistry, shell linear extension and calcification during calcein staining and 45Ca experiments with pteropod Limacina helicina, 2009

Thecosome pteropods (shelled pelagic molluscs) can play an important role in the food web of various ecosystems and play a key role in the cycling of carbon and carbonate. Since they harbor an aragonitic shell, they could be very sensitive to ocean acidification driven by the increase of anthropogenic CO2 emissions. The impact of changes in the carbonate chemistry was investigated on Limacina helicina, a key species of Arctic ecosystems. Pteropods were kept in culture under controlled pH conditions corresponding to pCO2 levels of 350 and 760 µatm. Calcification was estimated using a fluorochrome and the radioisotope 45Ca. It exhibits a 28 % decrease at the pH value expected for 2100 compared to the present pH value. This result supports the concern for the future of pteropods in a high-CO2 world, as well as of those species dependent upon them as a food resource. A decline of their populations would likely cause dramatic changes to the structure, function and services of polar ecosystems.

Structure function and Multifractal spectrum applied to Digital Elevation Model

A Digital Elevation Model (DEM) provides the information basis used for many geographic applications such as topographic and geomorphologic studies, landscape through GIS (Geographic Information Systems) among others. The DEM capacity to represent Earth?s surface depends on the surface roughness and the resolution used. Each DEM pixel depends on the scale used characterized by two variables: resolution and extension of the area studied. DEMs can vary in resolution and accuracy by the production method, although there are statistical characteristics that keep constant or very similar in a wide range of scales. Based on this property, several techniques have been applied to characterize DEM through multiscale analysis directly related to fractal geometry: multifractal spectrum and the structure function. The comparison of the results by both methods is discussed. The study area is represented by a 1024 x 1024 data matrix obtained from a DEM with a resolution of 10 x 10 m each point, which correspond with a region known as ?Monte de El Pardo? a property of Spanish National Heritage (Patrimonio Nacional Español) of 15820 Ha located to a short distance from the center of Madrid. Manzanares River goes through this area from North to South. In the southern area a reservoir is found with a capacity of 43 hm3, with an altitude of 603.3 m till 632 m when it is at the highest capacity. In the middle of the reservoir the minimum altitude of this area is achieved.

A fuzzy extension of MAGERIT methodology for risk analysis in information systems

We propose a fuzzy approach to deal with risk analysis for information systems. We extend MAGERIT methodology that valuates the asset dependencies to a fuzzy framework adding fuzzy linguistic terms to valuate the different elements (terminal asset values, asset dependencies as well as the probability of threats and the resulting asset degradation) in risk analysis. Computations are based on the trapezoidal fuzzy numbers associated with these linguistic terms and, finally, the results of these operations are translated into a linguistic term by means of a similarity function.

Extension of the thermodynamics of small systems to open metastable states: An example

By using a simplified model of small open liquid-like clusters with surface effects, in the gas phase, it is shown how the statistical thermodynamics of small systems can be extended to include metastable supersaturated gaseous states not too far from the gas–liquid equilibrium transition point. To accomplish this, one has to distinguish between mathematical divergence and physical convergence of the open-system partition function.

The cell surface metalloprotease/disintegrin Kuzbanian is required for axonal extension in Drosophila

It has long been suspected that proteolytic activity associated with advancing growth cones may be required for axon extension. We have isolated mutations in the kuzbanian (kuz) gene, which is expressed in the nervous system and encodes a putative zinc metalloprotease with a disintegrin domain. Drosophila embryos with loss-of-function mutations in kuz have dramatic defects in the development of central nervous system axon pathways, with many axons stalling and failing to extend through the nerve cord. This phenotype is rescued by panneural expression of kuz mRNA in the embryo. These results show that the Kuz metalloprotease is required for axon extension, suggesting a requirement for proteolytic activity at the growth cone surface.

Structure and function in rhodopsin: Topology of the C-terminal polypeptide chain in relation to the cytoplasmic loops*

Cysteine mutagenesis and site-directed spin labeling in the C-terminal region of rhodopsin have been used to probe the local structure and proximity of that region to the cytoplasmic loops. Each of the native amino acids in the sequence T335–T340 was replaced with Cys, one at a time. The sulfhydryl groups of all mutants reacted rapidly with the sulfhydryl reagent 4,4′-dithiodipyridine, which indicated a high degree of solvent accessibility. Furthermore, to probe the proximity relationships, a series of double Cys mutants was constructed. One Cys in all sets was at position 338 and the other was at a position in the sequence S240–V250 in the EF interhelical loop, at position 65 in the AB interhelical loop, or at position 140 in the CD interhelical loop. In the dark state, no significant disulfide formation was observed between C338 and C65 or C140 under the conditions used, whereas a relatively rapid disulfide formation was observed between C338 and C242 or C245. Spin labels in the double Cys mutants showed the strongest magnetic interactions between the nitroxides attached to C338 and C245 or C246. Light activation of the double mutant T242C/S338C resulted in slower disulfide formation, whereas interactions between nitroxides at C338 and C245 or C246 decreased. These results suggest the proximity of the C-terminal residue C338 to residues located on the outer face of a cytoplasmic helical extension of the F helix with an apparent increase of distance upon photoactivation.

The Myosin I SH3 Domain and TEDS Rule Phosphorylation Site are Required for In Vivo Function

The class I myosins play important roles in controlling many different types of actin-based cell movements. Dictyostelium cells either lacking or overexpressing amoeboid myosin Is have significant defects in cortical activities such as pseudopod extension, cell migration, and macropinocytosis. The existence of Dictyostelium null mutants with strong phenotypic defects permits complementation analysis as a means of exploring important functional features of the myosin I heavy chain. Mutant Dictyostelium cells lacking two myosin Is exhibit profound defects in growth, endocytosis, and rearrangement of F-actin. Expression of the full-length myoB heavy chain in these cells fully rescues the double mutant defects. However, mutant forms of the myoB heavy chain in which a serine at the consensus phosphorylation site has been altered to an alanine or in which the C-terminal SH3 domain has been removed fail to complement the null phenotype. The wild-type and mutant forms of the myoB heavy chain appeared to be properly localized when they were expressed in the myosin I null mutants. These results suggest that the amoeboid myosin I consensus phosphorylation site and SH3 domains do not play a role in the localization of myosin I, but are absolutely required for in vivo function.

A database and tools for 3-D protein structure comparison and alignment using the Combinatorial Extension (CE) algorithm

The database reported here is derived using the Combinatorial Extension (CE) algorithm which compares pairs of protein polypeptide chains and provides a list of structurally similar proteins along with their structure alignments. Using CE, structure–structure alignments can provide insights into biological function. When a protein of known function is shown to be structurally similar to a protein of unknown function, a relationship might be inferred; a relationship not necessarily detectable from sequence comparison alone. Establishing structure–structure relationships in this way is of great importance as we enter an era of structural genomics where there is a likelihood of an increasing number of structures with unknown functions being determined. Thus the CE database is an example of a useful tool in the annotation of protein structures of unknown function. Comparisons can be performed on the complete PDB or on a structurally representative subset of proteins. The source protein(s) can be from the PDB (updated monthly) or uploaded by the user. CE provides sequence alignments resulting from structural alignments and Cartesian coordinates for the aligned structures, which may be analyzed using the supplied Compare3D Java applet, or downloaded for further local analysis. Searches can be run from the CE web site, http://cl.sdsc.edu/ce.html, or the database and software downloaded from the site for local use.

Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production

Single-gene mutations that extend lifespan provide valuable tools for the exploration of the molecular basis for age-related changes in cell and tissue function and for the pathophysiology of age-dependent diseases. We show here that mice homozygous for loss-of-function mutations at the Pit1 (Snell dwarf) locus show a >40% increase in mean and maximal longevity on the relatively long-lived (C3H/HeJ × DW/J)F1 background. Mutant dwJ/dw animals show delays in age-dependent collagen cross-linking and in six age-sensitive indices of immune system status. These findings thus demonstrate that a single gene can control maximum lifespan and the timing of both cellular and extracellular senescence in a mammal. Pituitary transplantation into dwarf mice does not reverse the lifespan effect, suggesting that the effect is not due to lowered prolactin levels. In contrast, homozygosity for the Ghrhrlit mutation, which like the Pit1dw mutation lowers plasma growth hormone levels, does lead to a significant increase in longevity. Male Snell dwarf mice, unlike calorically restricted mice, become obese and exhibit proportionately high leptin levels in old age, showing that their exceptional longevity is not simply due to alterations in adiposity per se. Further studies of the Pit1dw mutant, and the closely related, long-lived Prop-1df (Ames dwarf) mutant, should provide new insights into the hormonal regulation of senescence, longevity, and late life disease.

Molecular cloning and sequence analysis of expansins--a highly conserved, multigene family of proteins that mediate cell wall extension in plants.

Expansins are unusual proteins discovered by virtue of their ability to mediate cell wall extension in plants. We identified cDNA clones for two cucumber expansins on the basis of peptide sequences of proteins purified from cucumber hypocotyls. The expansin cDNAs encode related proteins with signal peptides predicted to direct protein secretion to the cell wall. Northern blot analysis showed moderate transcript abundance in the growing region of the hypocotyl and no detectable transcripts in the nongrowing region. Rice and Arabidopsis expansin cDNAs were identified from collections of anonymous cDNAs (expressed sequence tags). Sequence comparisons indicate at least four distinct expansin cDNAs in rice and at least six in Arabidopsis. Expansins are highly conserved in size and sequence (60-87% amino acid sequence identity and 75-95% similarity between any pairwise comparison), and phylogenetic trees indicate that this multigene family formed before the evolutionary divergence of monocotyledons and dicotyledons. Sequence and motif analyses show no similarities to known functional domains that might account for expansin action on wall extension. A series of highly conserved tryptophans may function in expansin binding to cellulose or other glycans. The high conservation of this multigene family indicates that the mechanism by which expansins promote wall extensin tolerates little variation in protein structure.

Predator-induced phenotypic plasticity in tadpoles: extension or innovation?

Phenotypic plasticity, the ability of a trait to change as a function of the environment, is central to many ideas in evolutionary biology. A special case of phenotypic plasticity observed in many organisms is mediated by their natural predators. Here, we used a predator-prey system of dragonfly larvae and tadpoles to determine if predator-mediated phenotypic plasticity provides a novel way of surviving in the presence of predators (an innovation) or if it represents a simple extension of the way noninduced tadpoles survive predation. Tadpoles of Limnodynastes peronii were raised in the presence and absence of predation, which then entered a survival experiment. Induced morphological traits, primarily tail height and tail muscle height, were found to be under selection, indicating that predator-mediated phenotypic plasticity may be adaptive. Although predator-induced animals survived better, the multivariate linear selection gradients were similar between the two tadpole groups, suggesting that predator-mediated phenotypic plasticity is an extension of existing survival strategies. In addition, nonlinear selection gradients indicated a cost of predator-induced plasticity that may limit the ability of phenotypic plasticity to enhance survival in the presence of predators.

Effects of early intensive postoperative physiotherapy on limb function after tibial plateau leveling osteotomy in dogs with deficiency of the cranial cruciate ligament

Objective-To determine effects of early intensive postoperative physiotherapy on limb function in dogs after tibial plateau leveling osteotomy (TPLO) for deficiency of the cranial cruciate ligament (CCL). Animals-8 adult dogs with CCL deficiency. Procedure-After TPLO, dogs underwent a physiotherapy program 3 times/wk (physiotherapy group; n = 4) or a walking program (home-exercise group; 4). All dogs were evaluated before surgery, 1 and 10 days after surgery, and 3 and 6 weeks after surgery. Thigh circumference (TC), stifle joint flexion and extension range of motion (ROM), lameness, and weight-bearing scores were recorded. Results-Before surgery, CCL-deficient limbs had significantly reduced TC and reduced flexion and extension ROMs, compared with values for the contralateral control limb. Six weeks after TPLO, the physiotherapy group had significantly larger TC than the home-exercise group, with the difference no longer evident between the affected and nonaffected limbs. Extension and flexion ROMs were significantly greater in the physiotherapy group, compared with values for the home-exercise group, 3 and 6 weeks after surgery. Six weeks after surgery, the difference in flexion and extension ROMs was no longer evident between the affected and nonaffected limbs in the physiotherapy group. Both groups had improvements for lameness and weight-bearing scores over time, but no difference was found between the 2 groups. Conclusions and Clinical Relevance-After TPLO in CCL-deficient dogs, early physiotherapy intervention should be considered as part of the postoperative management to prevent muscle atrophy, build muscle mass and strength, and increase stifle joint flexion and extension ROMs.