The influence of sagittal center of pressure offset on gait kinematics and kinetics

ObjectivesKinetic patterns of the lower extremity joints have been shown to be influenced by modification of the location of the center of pressure (CoP) of the foot. The accepted theory is that a shifted location of the CoP alters the distance between the ground reaction force and the center of the joint, thereby modifying torques during gait. Various footwear designs have been reported to significantly alter the magnitude of sagittal joint torques during gait. However, the relationship between the CoP and the kinetic patterns in the sagittal plane has not been examined. The aim of this study was to evaluate the association between the sagittal location of the CoP and gait patterns during gait in healthy men.MethodsA foot-worn biomechanical device which allows controlled manipulation of the CoP location was utilized. Fourteen healthy men underwent successive gait analysis with the device set to convey three different sagittal locations of the CoP: neutral, anterior offset and posterior offset.ResultsCoP translation in the sagittal plane (i.e., from posterior to anterior) significantly related with an ankle dorsiflexion torque and a knee extension torque shift throughout the stance phase. Likewise, an anterior translation of the CoP significantly reduced the extension torque at the hip during pre-swing.ConclusionsThe study results confirm a direct correlation between sagittal offset of the CoP and the magnitude of joint torques throughout the lower extremity.     

QSOX contains a pseudo-dimer of functional and degenerate sulfhydryl oxidase domains

Quiescin sulfhydryl oxidase (QSOX) catalyzes formation of disulfide bonds between cysteine residues in substrate proteins. Human QSOX1 is a multi-domain, monomeric enzyme containing a module related to the single-domain sulfhydryl oxidases of the Erv family. A partial QSOX1 crystal structure reveals a single-chain pseudo-dimer mimicking the quaternary structure of Erv enzymes. However, one pseudo-dimer “subunit” has lost its cofactor and catalytic activity. In QSOX evolution, a further concatenation to a member of the protein disulfide isomerase family resulted in an enzyme capable of both disulfide formation and efficient transfer to substrate proteins.     

Wet electron microscopy with quantum dots

Wet electron microscopy (EM) is a new imaging method with the potential to allow higher spatial resolution of samples. In contrast to most EM methods, it requires little time to perform and does not require complicated equipment or difficult steps. We used this method on a common murine macrophage cell line, IC-21, in combination with various stains and preparations, to collect high resolution images of the actin cytoskeleton. Most importantly, we demonstrated the use of quantum dots in conjunction with this technique to perform light/electron correlation microscopy. We found that wet EM is a useful tool that fits into a niche between the simplicity of light microscopy and the high spatial resolution of EM.     

Innate immunity in multiple sclerosis: myeloid dendritic cells in secondary progressive multiple sclerosis are activated and drive a proinflammatory immune response

Multiple sclerosis (MS) is postulated to be a T cell-mediated autoimmune disease characterized clinically by a relapsing-remitting (RR) stage followed by a secondary progressive (SP) phase. The progressive phase is felt to be secondary to neuronal degenerative changes triggered by inflammation. The status of the innate immune system and its relationship to the stages of MS is not well understood. Dendritic cells (DCs) are professional APCs that are central cells of the innate immune system and have the unique capacity to induce primary immune responses. We investigated circulating myeloid DCs isolated directly from the blood to determine whether there were abnormalities in myeloid DCs in MS and whether they were related to disease stage. We found that SP-MS subjects had an increased percentage of DCs expressing CD80, a decreased percentage expressing PD-L1, and an increased percentage producing IL-12 and TNF-alpha compared with RR-MS or controls. A higher percentage of DCs from both RR and SP-MS patients expressed CD40 compared with controls. We then investigated the polarization effect of DCs from MS patients on naive T cells taken from cord blood using a MLR assay. Whereas DCs from RR-MS induced higher levels of Th1 (IFN-gamma, TNF-alpha) and Th2 (IL-4, IL-13) cytokines compared with controls, DCs from SP-MS only induced a polarized Th1 response. These results demonstrate abnormalities of DCs in MS and may explain the immunologic basis for the different stages and clinical patterns of MS.     

Genome sequencing and mapping reveal loss of heterozygosity as a mechanism for rapid adaptation in the vegetable pathogen Phytophthora capsici

The oomycete vegetable pathogen Phytophthora capsici has shown remarkable adaptation to fungicides and new hosts. Like other members of this destructive genus, P. capsici has an explosive epidemiology, rapidly producing massive numbers of asexual spores on infected hosts. In addition, P. capsici can remain dormant for years as sexually recombined oospores, making it difficult to produce crops at infested sites, and allowing outcrossing populations to maintain significant genetic variation. Genome sequencing, development of a high-density genetic map, and integrative genomic or genetic characterization of P. capsici field isolates and intercross progeny revealed significant mitotic loss of heterozygosity (LOH) in diverse isolates. LOH was detected in clonally propagated field isolates and sexual progeny, cumulatively affecting >30% of the genome. LOH altered genotypes for more than 11,000 single-nucleotide variant sites and showed a strong association with changes in mating type and pathogenicity. Overall, it appears that LOH may provide a rapid mechanism for fixing alleles and may be an important component of adaptability for P. capsici.     

Reduction in knee adduction moment via non-invasive biomechanical training: a longitudinal gait analysis study

Biomechanical non-invasive interventions have been previously reported to reduce pain and facilitate superior levels of function in patients with medial knee osteoarthritis [OA]. One such treatment is the AposTherapy, a customized program utilizing a foot-worn biomechanical device allowing center of pressure modification and continuous perturbation during gait. The influence of this intervention on objective gait metrics has yet to be determined. The aim of the current study was to prospectively examine changes in kinetic and kinematic parameters in patients enrolled in this treatment program. Twenty-five females with symptomatic bilateral medial compartment knee OA were enrolled in the customized daily treatment program. All patients underwent barefoot gait analysis testing and completed subjective questionnaires prior to treatment initiation and on two follow-up visits. Significantly reduced knee adduction moment (KAM) magnitude was noted during barefoot walking after three and nine months of treatment. On average, the knee adduction impulse and the 1st and 2nd KAM peaks were reduced by 13%, 8.4%, and 12.7%, respectively. Furthermore, moment reduction was accompanied by elevated walking velocity, significant pain reduction, and increased functional activity. In addition to symptomatic improvement, our results suggest that this treatment program can alter kinetic gait parameters in this population. We speculate that these adaptations account for the symptomatic and functional improvement reported for this intervention.     

Genome assembly of bell pepper endornavirus from small RNA

The family Endornaviridae infects diverse hosts, including plants, fungi, and oomycetes. Here we report for the first time the assembly of bell pepper endornavirus by next-generation sequencing of viral small RNA. Such a population of small RNA indicates the activation of the viral immunity silencing machinery by this cryptic virus, which probably encodes a novel silencing suppressor.     

End-binding protein 1 controls signal propagation from the T cell receptor

The role of microtubules (MTs) in the control and dynamics of the immune synapse (IS) remains unresolved. Here, we show that T cell activation requires the growth of MTs mediated by the plus-end specific protein end-binding 1 (EB1). A direct interaction of the T cell receptor (TCR) complex with EB1 provides the molecular basis for EB1 activity promoting TCR encounter with signalling vesicles at the IS. EB1 knockdown alters TCR dynamics at the IS and prevents propagation of the TCR activation signal to LAT, thus inhibiting activation of PLCγ1 and its localization to the IS. These results identify a role for EB1 interaction with the TCR in controlling TCR sorting and its connection with the LAT/PLCγ1 signalosome.     

Disentangling signaling gradients generated by equivalent sources

Yeast cells approach a mating partner by polarizing along a gradient of mating pheromones that are secreted by cells of the opposite mating type. The Bar1 protease is secreted by a-cells and, paradoxically, degrades the α-factor pheromones which are produced by cells of the opposite mating type and trigger mating in a-cells. This degradation may assist in the recovery from pheromone signaling but has also been shown to play a positive role in mating. Previous studies suggested that widely diffusing protease can bias the pheromone gradient towards the closest secreting cell. Here, we show that restricting the Bar1 protease to the secreting cell itself, preventing its wide diffusion, facilitates discrimination between equivalent mating partners. This may be mostly relevant during spore germination, where most mating events occur in nature.