Acoustic transmission in normal human hips: structural testing of joint symmetry

An acoustical technique has been developed for the measurement of structural symmetry of the hip joints. A mild vibratory force was applied to the sacrum and sound signals were picked up at both hips by a pair of microphones installed in two stethoscopes. These stethoscope–microphone assembles were calibrated to achieve a difference in relative sensitivity of less than 0.2 dB. The relative transmission of sound signals was analysed and compared between both hips by a dual-channel signal analyser. Twenty-seven healthy adults, 20 healthy pre-school children and 19 normal neonates were tested. Results from these three groups showed high coherence of the sound signals and that the discrepancy between both hips was smallest in the frequency range of 200–315 Hz. For normal neonates, the sound signals maintained a high coherence (γ²>0.97) and small discrepancy (D<1.25 dB) between both hips. This study has shown that the acoustical technique provides a practical structural testing for bony symmetry of the hips and the results offer a baseline for further investigation into developmental dysplasia of the hip (DDH) in neonates. Clinical screening for DDH is still problematic in developing countries.     

Nano-C60 cytotoxicity is due to lipid peroxidation

This study examines the biological effects of water-soluble fullerene aggregates in an effort to evaluate the fundamental mechanisms that contribute to the cytotoxicity of a classic engineered nanomaterial. For this work we used a water-soluble fullerene species, nano-C₆₀, a fullerene aggregate that readily forms when pristine C₆₀ is added to water. Nano-C₆₀ was cytotoxic to human dermal fibroblasts, human liver carcinoma cells (HepG2), and neuronal human astrocytes at doses 50 ppb (LC₅₀=2–50 ppb, depending on cell type) after 48 h exposure. This water-soluble nano-C₆₀ colloidal suspension disrupts normal cellular function through lipid peroxidation; reactive oxygen species are responsible for the membrane damage. Cellular viability was determined through live/dead staining and LDH release. DNA concentration and mitochondrial activity were not affected by the nano-C₆₀ inoculations to cells in culture. The integrity of cellular membrane was examined by monitoring the peroxy-radicals on the lipid bilayer. Subsequently, glutathione production was measured to assess the cell's reaction to membrane oxidation. The damage to cell membranes was observed both with chemical assays, and confirmed physically by visualizing membrane permeability with high molecular weight dyes. With the addition of an antioxidant, l-ascorbic acid, the oxidative damage and resultant toxicity of nano-C₆₀ was completely prevented.     

Nature's Swiss Army Knife: The Diverse Protective Roles of Anthocyanins in Leaves

Anthocyanins, the pigments responsible forspectacular displays of vermilion in the leaves of deciduoustrees, have long been considered an extravagant waste of aplant's resources. Contemporary research, in contrast, has begunto show that the pigments can significantly influence the way aleaf responds to environmental stress. Anthocyanins have beenimplicated in tolerance to stressors as diverse as drought,UV-B, and heavy metals, as well as resistance toherbivores and pathogens. By absorbing high-energy quanta,anthocyanic cell vacuoles both protect chloroplasts from thephotoinhibitory and photooxidative effects of strong light, andprevent the catabolism of photolabile defence compounds.Anthocyanins also mitigate photooxidative injury in leaves byefficiently scavenging free radicals and reactive oxygen species.Far from being a useless by-product of the flavonoid pathway,these red pigments may in some instances be critical for plant survival.     

Retroposed new genes out of the X in Drosophila

New genes that originated by various molecular mechanisms are an essential component in understanding the evolution of genetic systems. We investigated the pattern of origin of the genes created by retroposition in Drosophila. We surveyed the whole Drosophila melanogaster genome for such new retrogenes and experimentally analyzed their functionality and evolutionary process. These retrogenes, functional as revealed by the analysis of expression, substitution, and population genetics, show a surprisingly asymmetric pattern in their origin. There is a significant excess of retrogenes that originate from the X chromosome and retropose to autosomes; new genes retroposed from autosomes are scarce. Further, we found that most of these X-derived autosomal retrogenes had evolved a testis expression pattern. These observations may be explained by natural selection favoring those new retrogenes that moved to autosomes and avoided the spermatogenesis X inactivation, and suggest the important role of genome position for the origin of new genes.     

The Neuroimmunology of Multiple Sclerosis: Possible Roles of T and B Lymphocytes in Immunopathogenesis

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system white matter. The association of the disease with MHC genes, the inflammatory white matter infiltrates, similarities with animal models, and the observation that MS can be treated with immunomodulatory and immunosuppressive therapies support the hypothesis that autoimmunity plays a major role in the disease pathology. Evidence supports activated CD4⁺ myelin-reactive T cells as major mediators of the disease. In addition, a renewed interest in the possible contribution of B cells to MS immunopathology has been sparked by nonhuman primate and MS pathological studies. This review focuses on the immunopathology of MS, outlining the hypothetical steps of tolerance breakdown and the molecules that play a role in the migration of autoreactive cells to the CNS. Particular focus is given to autoreactive T cells and cytokines as well as B cells and autoantibodies and their role in CNS pathogenesis in MS.     

Legionella pneumophila serogroup 4 isolated from joint tissue

We report the isolation of Legionella pneumophila serogroup 4 from synovial tissue obtained from an 80-year-old female with chronic swelling of her right metacarpophalangeal joint. Synovial tissue infections caused by L. pneumophila are rare. Interestingly, this isolate was recovered from chocolate agar after 5 days of incubation.     

Expression of nonclassical MHC class Ib genes: comparison of regulatory elements

Peptide binding proteins of the major histocompatibility complex consist of the "classical" class Ia and "nonclassical" class Ib genes. The gene organization and structure/function relationship of the various exons comprising class I proteins are very similar among the class Ia and class Ib genes. Although the tissue-specific patterns of expression of these two gene families are overlapping, many class Ib genes are distinguished by relative low abundance and/or limited tissue distribution. Further, many of the class Ib genes serve specialized roles in immune responses. Given that the coding sequences of the class Ia and class Ib genes are highly homologous we sought to examine the promoter regions of the various class Ib genes by comparison to the well characterized promoter elements regulating expression of the class Ia genes. This analysis revealed a surprising complexity of promoter structures among all class I genes and few instances of conservation of class Ia promoter regulatory elements among the class Ib genes.     

How is electrical stimulation of the brain experienced,and how can we tell? Selected considerations on sensorimotor function and speech

ABSTRACT

Electrical stimulation of the nervous system is a powerful tool for localizing and examining the function of numerous brain regions. Delivered to certain regions of the cerebral cortex, electrical stimulation can evoke a variety of first-order effects, including observable movements or an urge to move, or somatosensory, visual, or auditory percepts. In still other regions the subject may be oblivious to the stimulation. Often overlooked, however, is whether the subject is aware of the stimulation, and if so, how the stimulation is experienced by the subject. In this review of how electrical stimulation has been used to study selected aspects of sensorimotor and language function, we raise questions that future studies might address concerning the subjects’ second-order experiences of intention and agency regarding evoked movements, of the naturalness of evoked sensory percepts, and of other qualia that might be evoked in the absence of an overt first-order experience.     

Intermittent preventive sulfadoxine-pyrimethamine treatment of primigravidae reduces levels of plasma immunoglobulin G, which protects against pregnancy-associated Plasmodium falciparum malaria

Pregnancy-associated malaria (PAM) is an important cause of maternal and neonatal suffering. It is caused by Plasmodium falciparum capable of inhabiting the placenta through expression of particular variant surface antigens (VSA) with affinity for proteoglycans such as chondroitin sulfate A. Protective immunity to PAM develops following exposure to parasites inhabiting the placenta, and primigravidae are therefore particularly susceptible to PAM. The adverse consequences of PAM in primigravidae are preventable by intermittent preventive treatment (IPTp), where women are given antimalarials at specified intervals during pregnancy, but this may interfere with acquisition of protective PAM immunity. We found that Kenyan primigravidae receiving sulfadoxine-pyrimethamine IPTp had significantly lower levels of immunoglobulin G (IgG) with specificity for the type of parasite-encoded VSA-called VSA(PAM)-that specifically mediate protection against PAM than did women receiving a placebo. VSA(PAM)-specific IgG levels depended on the number of IPTp doses received and were sufficiently low to be of clinical concern among multidose recipients. Our data suggest that IPTp should be extended to women of all parities, in line with current World Health Organization recommendations.     

Gene Therapy: The Potential Applicability of Gene Transfer Technology to the Human Germline

The theoretical possibility of applying gene transfer methodologies to the human germline is explored. Transgenic methods for genetically manipulating embryos may in principle be applied to humans. In particular, microinjection of retroviral vector appears to hold the greatest promise, with transgenic primates already obtained from this approach. Sperm-mediated gene transfer offers potentially the easiest route to the human germline, however the requisite methodology is presently underdeveloped. Nuclear transfer (cloning) offers an alternative approach to germline genetic modification, however there are major health concerns associated with current nuclear transfer methods. It is concluded that human germline gene therapy remains for all practical purposes a future possibility that must await significant and important advances in gene transfer technology.