The effect of weightbearing and external loading on anterior cruciate ligament strain

A force balance between the ligaments, articular contact, muscles and body weight maintains knee joint stability. Thus, it is important to study anterior cruciate ligament (ACL) biomechanics, in vivo, under weightbearing conditions. Our objective was to compare the ACL strain response under weightbearing and non-weightbearing conditions and in combination with three externally applied loadings: (1) anterior-posterior shear forces, (2) internal-external torques, and (3) varus-valgus moments. A strain transducer was implanted on the ACL of 11 subjects. All joint loadings were performed with the knee at 20 degrees of flexion. A significant increase in ACL strain was observed as the knee made the transition from non-weightbearing to weightbearing. During anterior shear loading, the strain values produced during weightbearing were greater than those of the non-weightbearing knee (shear loads <40N). At higher shear loads, the strain values became equal. During axial torsion, an internal torque of 10Nm strained the ACL when the knee was non-weightbearing while an equivalent external torque did not. Weightbearing significantly increased ACL strain values in comparison to non-weightbearing with the application of external torques and low internal torques (<3Nm). The strains became equal for higher internal torques. For V-V loading, the ACL was not strained in the non-weightbearing knee. However, weightbearing increased the ACL strain values over the range of moments tested. These data have important clinical ramifications in the development of rehabilitation protocols following ACL reconstruction since weightbearing has been previously thought to provide a protective mechanism to the healing graft.     

Biomechanical response to acupuncture needling in humans.

During acupuncture treatments, acupuncture needles are manipulated to elicit the characteristic "de qi" reaction widely viewed as essential to acupuncture's therapeutic effect. De qi has a biomechanical component, "needle grasp," which we have quantified by measuring the force necessary to pull an acupuncture needle out of the skin (pullout force) in 60 human subjects. We hypothesized that pullout force is greater with both bidirectional needle rotation (BI) and unidirectional rotation (UNI) than no rotation (NO). Acupuncture needles were inserted, manipulated, and pulled out by using a computer-controlled acupuncture needling instrument at eight acupuncture points and eight control points. We found 167 and 52% increases in mean pullout force with UNI and BI, respectively, compared with NO (repeated-measures ANOVA, P < 0.001). Pullout force was on average 18% greater at acupuncture points than at control points (P < 0.001). Needle grasp is therefore a measurable biomechanical phenomenon associated with acupuncture needle manipulation.     

Increased heat sensitivity of photosynthesis in tobacco plants with reduced Rubisco activase

High temperature inhibits photosynthesis by several mechanisms including deactivation of Rubisco. The inhibition of photosynthesis by high temperature and its relationship to Rubisco deactivation was studied using tobacco (Nicotiana tabaccum L. cv W38) transformed with a Rubisco activase gene inserted in the antisense orientation and untransformed controls. High temperature (42 °C) reduced photosynthesis in both lines of plants. However, photosynthesis recovered nearly completely in wild-type plants and very little in plants lacking Rubisco activase. The F₀ level of chlorophyll fluorescence decreased and q_N increased in the control plants during heating. In the antisense plants, q_N was always high and F₀ increased slightly during heat stress. NADP-malate dehydrogenase activation was unaffected by heat stress in control plants but was increased in the transgenic plants, consistent with a high redox status in the chloroplast. In wild-type plants, the inhibition of photosynthesis could be explained by a reversible decarbamylation of Rubisco and an acceptor-side limitation imposed on photosynthetic electron transport. However, in the anti-activase plants, carbamylation was low and constant and could not explain how photosynthesis was reduced at high temperature. Because ribulose bisphosphate was saturating at high temperature, the reduction in photosynthesis must have been caused by some impairment of Rubisco function not reflected in measurements of activation state or carbamylation status. This in vivo Rubisco impairment was not relieved upon return to lower temperature. We speculate that the reversible decarbamylation of Rubisco at moderately high temperature may be a protective mechanism by which the plant avoids more serious effects on Rubisco and the rest of the photosynthetic apparatus.This revised version was published online in October 2005 with corrections to the Cover Date.     

Network-based prediction and analysis of HIV dependency factors

HIV Dependency Factors (HDFs) are a class of human proteins that are essential for HIV replication, but are not lethal to the host cell when silenced. Three previous genome-wide RNAi experiments identified HDF sets with little overlap. We combine data from these three studies with a human protein interaction network to predict new HDFs, using an intuitive algorithm called SinkSource and four other algorithms published in the literature. Our algorithm achieves high precision and recall upon cross validation, as do the other methods. A number of HDFs that we predict are known to interact with HIV proteins. They belong to multiple protein complexes and biological processes that are known to be manipulated by HIV. We also demonstrate that many predicted HDF genes show significantly different programs of expression in early response to SIV infection in two non-human primate species that differ in AIDS progression. Our results suggest that many HDFs are yet to be discovered and that they have potential value as prognostic markers to determine pathological outcome and the likelihood of AIDS development. More generally, if multiple genome-wide gene-level studies have been performed at independent labs to study the same biological system or phenomenon, our methodology is applicable to interpret these studies simultaneously in the context of molecular interaction networks and to ask if they reinforce or contradict each other.     

Quantitative nuclear magnetic resonance to measure fat mass in infants and children

Quantitative nuclear magnetic resonance (QMR) is being used in human adults to obtain measures of total body fat mass (FM) with high precision. The current study assessed a device specially designed to accommodate infants and children between 3 and 50 kg (EchoMRI-AH). Body composition of 113 infants and children (3.3-49.9 kg) was assessed using dual-energy X-ray absorptiometry (DXA), air displacement plethysmography (ADP, PeaPod for infants ≤ 8 kg and BodPod for children ≥ 6 years) and QMR. Results were compared with the deuterium oxide dilution technique (D(2)O) and a four-compartment model (4-C). The percentages of compliance were: 98% QMR; 75% DXA; 94% BodPod; and 95% PeaPod. Although QMR precision was high (coefficient of variation = 1.42%), it overestimated FM ~10% compared to the 4-C model and underestimated FM by ~4% compared to the deuterium method in children ≥ 6 years. QMR was less concordant with 4-C or D(2)O models for infants ≤ 8 kg. Thus, a piece-wise defined model for mathematically fitting the QMR data to the D(2)O data was employed and this adjustment improved the accuracy relative to D(2)O and 4-C for infants. Our results suggest that the pediatric QMR with appropriate mathematical adjustment provides a fast and precise method for assessing FM longitudinally in infants and in children weighing up to 50 kg.