Septal aperture aetiology: still more questions than answers

Many theories have been suggested in order to explain the aetiology of septal aperture. The influence of genes, the size and shape of ulna processes, joint laxity, bone robusticity, osteoarthritis, and osteoporosis has been discussed; however, the problem has not yet been solved. The aim of the study was to examine the correlations between musculoskeletal stress markers, humeral robusticity and septal aperture. Additionally, the frequency of septal aperture according to sex, age, and skeletal side had been analysed. The skeletal material had come from a medieval cemetery in Cedynia, Poland. Skeletons of 201 adults (102 males, 99 females) had been examined and septal aperture had been scored. Six muscle attachment sites of upper limb bones had been analysed. Humeral robusticity had been calculated by use of the humeral robusticity index. The frequency of septal aperture among the population from Cedynia is 7.5%. There are no differences in septal aperture prevalence between males and females, the skeletal sides or age groups. In the analysed material, males with less developed muscle markers of right upper bones proved a higher predictable rate in having septal aperture (R = –0.34). On the left bones and among females, the converse correlation had also been found, but it is not statistically significant. The correlation between septal aperture and humeral robusticity is converse, yet small and insignificant. These results can confirm the theory of joint laxity and suggest that stronger bones (heavier muscles, more robust bones) increase joint tightness, and therefore protect the humeral lamina from septal aperture formation. But this theory needs a further detailed analysis

Kinematic Synthesis of Planar, Shape-Changing, Rigid Body Mechanisms for Design Profiles with Significant Differences in Arc Length

This paper presents a kinematic procedure to synthesize planar mechanisms capable of approximating a shape change defined by a general set of curves. These “morphing curves,” referred to as design profiles, differ from each other by a combination of displacement in the plane, shape variation, and notable differences in arc length. Where previous rigid-body shape-change work focused on mechanisms composed of rigid links and revolute joints to approximate curves of roughly equal arc length, this work introduces prismatic joints into the mechanisms in order to produce the different desired arc lengths. A method is presented to iteratively search along the profiles for locations that are best suited for prismatic joints. The result of this methodology is the creation of a chain of rigid bodies connected by revolute and prismatic joints that can approximate a set of design profiles

Kinetic Characterisation of a Single Chain Antibody against the Hormone Abscisic Acid: Comparison with Its Parental Monoclonal

A single-chain Fv fragment antibody (scFv) specific for the plant hormone abscisic acid (ABA) has been expressed in the bacterium Escherichia coli as a fusion protein. The kinetics of ABA binding have been measured using surface plasmon resonance spectrometry (BIAcore 2000) using surface and solution assays. Care was taken to calculate the concentration of active protein in each sample using initial rate measurements under conditions of partial mass transport limitation. The fusion product, parental monoclonal antibody and the free scFv all have low nanomolar affinity constants, but there is a lower dissociation rate constant for the parental monoclonal resulting in a three-fold greater affinity. Analogue specificity was tested and structure-activity binding preferences measured. The biologically-active (+)-ABA enantiomer is recognised with an affinity three orders of magnitude higher than the inactive (-)-ABA. Metabolites of ABA including phaseic acid, dihydrophaseic acid and deoxy-ABA have affinities over 100-fold lower than that for (+)-ABA. These properties of the scFv make it suitable as a sensor domain in bioreporters specific for the naturally occurring form of ABA

Design and Implementation of an Instrumented Cane for Gait Recognition

Independent mobility is an important aspect of an individual's life and must sometimes be augmented by use of an assistive device such as a wheeled walker or cane following a fall, injury, or functional decline. Physical therapists perform functional gait assessments to gauge the probability of an individual experiencing a fall and often recommend use of a walker, cane, or walking stick to decrease fall risk. Our team has developed a clinical assessment tool centered on a standard walking cane embedded system that can enhance a therapist's observation-based gait assessment with use of additional objective and quantitative data. This system can be utilized to detect timing and speed of cane placement, angular acceleration of the cane, and amounts of weight borne on the cane. This system is designed to assist physical therapists at the basic level in collection of objective data during gait analysis, to facilitate appropriate assistive gait device prescription, to provide patients and therapists feedback during gait training, and to reduce wrist and shoulder injuries with cane usage. However, more importantly, using the plethora of objective data that can be obtained from this cane, automated gait analysis and gait pattern classification can be performed to understand a patient's walking performance

Two types of bone necrosis in the middle triassic pistosaurus longaevus bones: The results of integrated studies

Avascular necrosis, diagnosed on the basis of either a specific pathological modification of the articular surfaces of bone or its radiologic appearance in vertebral centra, has been recognized in many Mesozoic marine reptiles as well as in present-day marine mammals. Its presence in the zoological and paleontologic record is usually associated with decompression syndrome, a disease that affects secondarily aquatic vertebrates that could dive. Bone necrosis can also be caused by infectious processes, but it differs in appearance from decompression syndrome-associated aseptic necrosis. Herein, we report evidence of septic necrosis in the proximal articular surface of the femur of a marine reptile, Pistosaurus longaevus, from the Middle Triassic of Poland and Germany. This is the oldest recognition of septic necrosis associated with septic arthritis in the fossil record so far, and the mineralogical composition of pathologically altered bone is described herein in detail. The occurrence of septic necrosis is contrasted with decompression syndrome-associated avascular necrosis, also described in Pistosaurus longaevus bone from Middle Triassic of Germany

Molecular basis for passive immunotherapy of Alzheimer's disease

Amyloid aggregates of the amyloid-{beta} (A{beta}) peptide are implicated in the pathology of Alzheimer's disease. Anti-A{beta} monoclonal antibodies (mAbs) have been shown to reduce amyloid plaques in vitro and in animal studies. Consequently, passive immunization is being considered for treating Alzheimer's, and anti-A{beta} mAbs are now in phase II trials. We report the isolation of two mAbs (PFA1 and PFA2) that recognize A{beta} monomers, protofibrils, and fibrils and the structures of their antigen binding fragments (Fabs) in complex with the A{beta}(1–8) peptide DAEFRHDS. The immunodominant EFRHD sequence forms salt bridges, hydrogen bonds, and hydrophobic contacts, including interactions with a striking WWDDD motif of the antigen binding fragments. We also show that a similar sequence (AKFRHD) derived from the human protein GRIP1 is able to cross-react with both PFA1 and PFA2 and, when cocrystallized with PFA1, binds in an identical conformation to A{beta}(1–8). Because such cross-reactivity has implications for potential side effects of immunotherapy, our structures provide a template for designing derivative mAbs that target A{beta} with improved specificity and higher affinity

The influence of warm ischemia elimination on kidney injury during transplantation - Clinical and molecular study

Kidney surface cooling was used during implantation to assess the effect of warm ischemia elimination on allograft function, histological changes and immune-related gene expression. 23 recipients were randomly assigned to a group operated on with kidney surface cooling during implantation (ice bag technique, IBT group), and the other 23 recipients receiving the contralateral kidney from the same donor were operated on with a standard technique. Three consecutive kidney core biopsies were obtained during the transplantation procedure: after organ recovery, after cold ischemia and after reperfusion. Gene expression levels were determined using low-density arrays (Format 32, TaqMan). The IBT group showed a significantly lower rate of detrimental events (delayed graft function and/or acute rejection, p = 0.015) as well as higher glomerular filtration rate on day 14 (p = 0.026). A greater decrease of MMP9 and LCN2 gene expression was seen in the IBT group during total ischemia (p = 0.003 and p = 0.018). Elimination of second warm ischemia reduced the number of detrimental events after kidney transplantation, and thus had influence on the short-term but not long-term allograft function. Surface cooling of the kidney during vascular anastomosis may reduce some detrimental effects of immune activation resulting from both brain death and ischemia-reperfusion injury

Aβ Peptide Fibrillar Architectures Controlled by Conformational Constraints of the Monomer

Anomalous self-assembly of the Aβ peptide into fibrillar amyloid deposits is strongly correlated with the development of Alzheimer's disease. Aβ fibril extension follows a template guided “dock and lock” mechanism where polymerisation is catalysed by the fibrillar ends. Using surface plasmon resonance (SPR) and quenched hydrogen-deuterium exchange NMR (H/D-exchange NMR), we have analysed the fibrillar structure and polymerisation properties of both the highly aggregation prone Aβ1–40 Glu22Gly (Aβ40Arc) and wild type Aβ1–40 (Aβ40WT). The solvent protection patterns from H/D exchange experiments suggest very similar structures of the fibrillar forms. However, through cross-seeding experiments monitored by SPR, we found that the monomeric form of Aβ40WT is significantly impaired to acquire the fibrillar architecture of Aβ40Arc. A detailed characterisation demonstrated that Aβ40WT has a restricted ability to dock and isomerise with high binding affinity onto Aβ40Arc fibrils. These results have general implications for the process of fibril assembly, where the rate of polymerisation, and consequently the architecture of the formed fibrils, is restricted by conformational constraints of the monomers. Interestingly, we also found that the kinetic rate of fibril formation rather than the thermodynamically lowest energy state determines the overall fibrillar structure