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Beyond the biomedical and behavioural: towards an integrated approach to HIV prevention in the southern African mining industry.

While migrant labour is believed to play an important role in the dynamics of HIV-transmission in many of the countries of southern Africa, little has been written about the way in which HIV/AIDS has been dealt with in the industrial settings in which many migrant workers are employed. This paper takes the gold mining industry in the countries of the Southern African Development Community (SADC) as a case study. While many mines made substantial efforts to establish HIV-prevention programmes relatively early on in the epidemic, these appear to have had little impact. The paper analyses the response of key players in the mining industry, in the interests of highlighting the limitations of the way in which both managements and trade unions have responded to HIV. It will be argued that the energy that has been devoted either to biomedical or behavioural prevention programmes or to human rights issues has served to obscure the social and developmental dimensions of HIV-transmission. This argument is supported by means of a case study which seeks to highlight the complexity of the dynamics of disease transmission in this context, a complexity which is not reflected in individualistic responses. An account is given of a new intervention which seeks to develop a more integrated approach to HIV management in an industrial setting.

Adult↗

Causes and effects of changes in xylem functionality in apple fruit.

BACKGROUND AND AIMS: The xylem in fruit of a number of species becomes dysfunctional as the fruit develops, resulting in a reduction of xylem inflow to the fruit. Such a reduction may have consequential effects on the mineral balance of the fruit. The aim of this study was to elucidate the dynamics and nature of xylem failure in developing apples (Malus domestica) showing differing susceptibilities to bitter pit, a calcium-related disorder. METHODS: Developmental changes in xylem functionality of the fruit were investigated in "Braeburn" and "Granny Smith" apples by using a dye infusion technique, to stain the vasculature along the path of dye movement. The vascular bundles were clearly visible in transverse section when fruit were sectioned equatorially. The intensity of staining of the vascular bundles in the fruit was recorded at regular intervals throughout the season. Tissue containing dysfunctional bundles was fixed and embedded in wax for subsequent sectioning and examination. KEY RESULTS: As the season progressed, an increasing proportion of vascular bundles failed to show any staining, with the most marked change occurring in the primary bundles, and in nearly all bundles with increasing distance from the stalk end of the fruit. Decreased conductance in the primary bundles of "Braeburn" occurred earlier than in "Granny Smith". Microscopy revealed that the xylem in vascular bundles of the fruit suffered substantial damage, indicating that the mode of dysfunction was via the physical disruption of the xylem caused by expansion of the flesh. CONCLUSIONS: Results support the view that the relative calcium deficiency of apple fruit is due to a progressive breakdown of xylem conductance caused by growth-induced damage to the xylem strand in the bundle. The earlier onset of xylem dysfunction in the cultivar more susceptible to bitter pit suggests that the relative growth dynamics of the fruit may control the occurrence of calcium-related disorders.

Biological Transport↗

Binding site for p120/delta-catenin is not required for Drosophila E-cadherin function in vivo.

Homophilic cell adhesion mediated by classical cadherins is important for many developmental processes. Proteins that interact with the cytoplasmic domain of cadherin, in particular the catenins, are thought to regulate the strength and possibly the dynamics of adhesion. beta-catenin links cadherin to the actin cytoskeleton via alpha-catenin. The role of p120/delta-catenin proteins in regulating cadherin function is less clear. Both beta-catenin and p120/delta-catenin are conserved in Drosophila. Here, we address the importance of cadherin-catenin interactions in vivo, using mutant variants of Drosophila epithelial cadherin (DE-cadherin) that are selectively defective in p120ctn (DE-cadherin-AAA) or beta-catenin-armadillo (DE-cadherin-Delta beta) interactions. We have analyzed the ability of these proteins to substitute for endogenous DE-cadherin activity in multiple cadherin-dependent processes during Drosophila development and oogenesis; epithelial integrity, follicle cell sorting, oocyte positioning, as well as the dynamic adhesion required for border cell migration. As expected, DE-cadherin-Delta beta did not substitute for DE-cadherin in these processes, although it retained some residual activity. Surprisingly, DE-cadherin-AAA was able to substitute for the wild-type protein in all contexts with no detectable perturbations. Thus, interaction with p120/delta-catenin does not appear to be required for DE-cadherin function in vivo.

Animals↗

Embryonic and larval expression of zebrafish voltage-gated sodium channel alpha-subunit genes.

Whereas it is known that voltage-gated calcium channels play important roles during development, potential embryonic roles of voltage-gated sodium channels have received much less attention. Voltage-gated sodium channels consist of pore-forming alpha-subunits (Na(v)1) and auxiliary beta-subunits. Here, we report the embryonic and larval expression patterns for all eight members of the gene family (scna) coding for zebrafish Na(v)1 proteins. We find that each scna gene displays a distinct expression pattern that is temporally and spatially dynamic during embryonic and larval stages. Overall, our findings indicate that scna gene expression occurs sufficiently early during embryogenesis to play developmental roles for both muscle and nervous tissues.

Amino Acid Sequence↗

Immotile-cilia syndrome and the cilia of the eye.

Ten patients with the immotile-cilia syndrome were subjected to an extensive eye examination, which failed to demonstrate any consistent single abnormality. The tests of the retinal function and the aqueous humor dynamics were normal. However, different corneal abnormalities--mostly without clinical significance--were observed in 9 out of 10 patients, suggesting a developmental disturbance.

Adult↗

Determination of air movement in stored grain as a factor in dynamic dispersion and distribution patterns of gaseous pesticides (fumigants).

The new research reported herein was motivated by variations in distribution-persistence patterns of fumigant residues (BERCK, 1974). The current developmental program is still underway. In the meantime, measurement of picoliter amounts of SF6 in air by GC equipped with a Ni63 EC detector has been proven useful over an airflow range of 10(-4) to 50 mph, representing a factor of 500,000 in differences in air velocity. Diverse applications have been outlined herein. This is the first case on record where measurement of unassisted airflow in the interstitial air of stored grain has been successfully executed, and which enabled determination of airflow speeds in the range of 0.5 to 7.5 times 10(-4) mph (=3 to 45 inches per hour).

Air Movements↗

Large-scale neural correlates of developmental dyslexia.

Recent work in the field of developmental dyslexia has emphasized the large-scale neural aspects of the disorder as measured by means of contemporary imaging techniques, electrophysiology, and post-mortem analyses. This article presents findings from these research domains and comprehensively reviews their relevance with respect to the behavioral and cognitive profiles of dyslexia. Large-scale alterations were observed in the perisylvian region across paradigms. Convergent evidence has also been reported in terms of hemispheric balance. Specifically, deviances in cerebral asymmetry associated with atypical organization of the left hemisphere were found in both children and adults with dyslexia. Emerging research encompassing high-temporal resolution methods such as magnetoencephalography (MEG) suggests right-hemisphere involvement and points to the complexity of the developmental disorder. A combined approach of structural imaging and MEG, and most importantly theory driven behavioral tasks may shed light on dynamics and trajectories of the neurobiology of dyslexia.

Adult↗

Human fetal central nervous system organotypic cultures.

Many aspects of human neurodevelopment remain enigmatic. A main reason for this is, although there have been a significant number of morphologic and biochemical studies of neural tissues derived from human embryos and fetuses, this can only provide a static picture of the events at a given gestational age. Also, in vitro studies that focus on cells derived from these tissues have a limitation in that different cell types in dissociated tissue culture cannot interact in a 'normal' physiologic manner thereby, perhaps, altering their housekeeping and luxury functions. The present study focused on the development of a human explant organotypic culture model that may overcome the static limitation of the first example and permit a dynamic analysis of different cell types as they interact which may satisfy the second restriction. Because there is an array of developmental markers that define different cell phenotypes, this explant model may also provide a means of analyzing, for the first time, processes undefined in the human CNS. Human fetal CNS tissue obtained from second trimester abortuses was established in culture. The tissues were maintained for up to 12 weeks during which time they developed and differentiated. Sample cultures were harvested periodically and analyzed by light- and electron microscopy in combination with immunocytochemistry. Differentiation of neurons, astrocytes, oligodendrocytes and endothelial cells was documented using morphologic and biochemical criteria. As such, this model system may allow for the analysis of processes that occur during normal human fetal neurodevelopment and in pathologic conditions.

Central Nervous System↗

Simple developmental programs of gene expression and cellular composition of lymphoid organs at the origin of natural tolerance.

Self-tolerance is acquired in the embryonic/perinatal period, but new lymphocytes (that will have to distinguish between self and nonself) continue to be produced throughout life, after both self and nonself are present. This makes it impossible for natural tolerance to rely on recessive mechanisms. Recent observations on "dominant tolerance" have led to the hypothesis that natural tolerance is established as a consequence of simple developmental programs for gene expression and cellular composition of primary lymphoid organs. In development, the cellular composition of the thymus is predominantly epithelial, allowing for the positive selection and activation of "high avidity" self-reactive T cells that are not deleted because antigen presentation by haemopoietic cells is limiting. Such T cells, activated in that environment, display effector functions of a regulatory type that are maintained in the periphery upon restimulation by tissue peptides shared with the thymic epithelium. Recent thymic emigrants with specificity for tissue-specific antigens that are absent from the thymus will first encounter their ligands in the context of the "regulatory cell" recognition of ubiquitous peptides and are thus recruited into similar regulatory activities. In contrast, thymic emigrants with specificity for nonself antigens (absent during the perinatal period) are not activated intrathymically, reach the periphery as resting cells, and move out of the time window of susceptibility to functional recruitment. These will react "de novo" upon encounter of the respective antigens and will acquire the class of effector functions determined by the peripheral microenvironment in which they are activated. This strategy, which explains the thymic dependence of peripheral tissue-specific tolerance, may be re-enforced by developmental restrictions in cytokine gene expression, and it will ensure the establishment and maintenance of T-cell tolerance through the dynamic storage of a distributed memory of the embryonic self. B lymphocytes that are produced in the embryonic/perinatal period characteristically rearrange and express a few V-genes very predominantly. These V-genes encode antibodies with unique properties of "connectivity" to other V-regions, making it possible to establish a network that limits clonal expansions and/or terminal differentiation to antibody production. Self-reactive B cells are thus recruited into such a network which, by contributing to the molecular environment of the body and to the selection of emergent repertoires, leads to deletion of connected cells and to the "normalization" of the adult antibody repertoires. Natural autoantibody repertoires in the adult are thus recursively maintained, stable and continuously adjusted to the thresholds of single cell deletion and to the alterations in the body composition. The activity of self-specific regulatory T cells contributes to limiting clonal expansion and inhibiting somatic mutation of self-reactive B cells. This model explains a number of observations that were not included in the "clonal" and "recessive" tolerance views, and offers suggestions on mechanisms in physiological autoimmunity and pathology.

Animals↗

Lens crystallins: gene recruitment and evolutionary dynamism.

In a novel evolutionary process, enzymes and stress proteins have undergone direct gene recruitment as eye lens crystallins in a number of independent events. This may have allowed a dynamic response to changing visual environment during evolution. In spite of their diversity, many crystallins may share an origin in essential developmental processes such as cell elongation.

Animals↗

Spatial, temporal, and cellular distribution of the activated extracellular signal regulated kinases 1 and 2 in the developing and mature rat cerebellum.

The extracellular signal regulated kinases 1 and 2 (ERK1/2) are important members of an intracellular signaling cascade that is involved in many aspects of the cellular physiology and development of neurons and glia. ERK1/2 are expressed in many brain regions including the cerebellum; however, their role during cerebellar development is poorly understood. Immunohistochemical approaches using phosphorylation-state specific antiserum that recognizes only the activated-ERK1/2 (pERK) were used to characterize the spatial and temporal patterns of activated-ERK in the developing and adult rat cerebellum. The distribution and cell type-specificity of pERK-immunoreactivity (IR) followed an age-related pattern, with the density of pERK-IR Purkinje cells decreasing between P6 and P15 and increasing at later times. Immunopositive granule cell neurons increased from P6 to P12, became decreased during much of late postnatal cerebellar development, and absent in adults. Co-localization of pERK with glial fibrillary acidic protein or the neuronal marker beta-tubulin revealed that activated ERK is present in maturing Purkinje and granule cells, and the soma of Bergmann glia on P4, P10 and P15; pERK was detected in astrocytes on P10 and P15. Associated with weaning, there was a general increase in activated-ERK in all cell types on P22. In adults, pERK-IR was confined to the Purkinje cell layer and scattered cells in the corpus medullare. In summary, a high degree of developmental plasticity was observed in the spatiotemporal distribution of cerebellar pERK-IR suggesting that the ERK-pathway plays a dynamic role in regulating neuronal and glial migration, proliferation and differentiation in the developing cerebellum. In the mature cerebellum, ERK signaling may also mediate postsynaptic information processing.

Analysis of Variance↗

Normal and pathological Tau proteins as factors for microtubule assembly.

Tau proteins are microtubule-associated proteins. They regulate the dynamics of the microtubule network, especially involved in the axonal transport and neuronal plasticity. Tau proteins belong to a family of developmentally regulated isoforms generated by alternative splicing and phosphorylation. This generates several Tau variants that interact with tubulin and other proteins. Therefore, Tau proteins are influenced by many physiological regulations. Tau proteins are also powerful markers of the neuronal physiological state. Their degree of phosphorylation is a good marker of cell integrity. It is heavily disturbed in numerous neurodegenerative disorders, leading to a collapse of the microtubule network and the presence of intraneuronal lesions resulting from Tau aggregation. However, different biochemical and immunological patterns of pathological Tau proteins found among neurodegenerative disorders are useful markers for the understanding of the role of Tau protein isoforms and the diagnosis of these pathological conditions.

Alzheimer Disease↗

The role of arthroscopic thermal capsulorrhaphy in the hip.

Arthroscopic thermal modification of collagen in the hip capsular tissue appears to be a treatment option for patients with hip instability. Traumatic hip instability is associated with frank dislocation or a subluxation, and labral tears. Atraumatic hip instability is associated with evidence of generalized ligament laxity. It can be associated with bone-collagen type disorders, including Ehlers-Danlos syndrome, Down syndrome, arthrochalasis multiplex congenita, developmental dysplastic hip, and idiopathic type. As previously discussed by Bellabarba et al, capsular laxity may be the underlying cause of dynamic hip instability. The capsule is a fibrous, thick, and strong structure that encircles the proximal femur and the acetabulum. The capsule is thicker anteriorly than posteriorly, and consists of two sets of fibers, circular and longitudinal. The capsule ligaments play a very important role in hip stability. The hip joint capsule is reinforced by the iliofemoral, pubofemoral, and ischiofemoral ligaments. It remains sensitive to stretch and serves as a mechanism for muscular feedback and pain. The iliofemoral ligament limits hyperextension and lateral rotation of the hip joint and is taut in full extension. Full extension of the hip exposes the capsule and ligaments to a twisting and shortening effect that forces the head onto the acetabulum. We are currently studying the effect of iliofemoral ligament deficiency and its relationship to instability. Many of the properties of synovial lubrication depend on contact with articular surfaces, and incongruency due to instability may have some functional role in distribution of synovial fluid, leading to stresses from weightbearing and eventually to rapid deterioration of the articular surfaces. The high-level athletes in this series include two professional baseball players, three professional golfers (PGA), one professional football player (NFL), one figure skater (Olympic gold medalist), one gymnast (Olympic level, bilateral hips), and one ballet dancer; they returned to their pre-injury level of activity. The other patients returned to their pre-injury functional lifestyle. Hip instability appears to present consistently with stable gait abnormalities and painful sensation of instability. Recognizing the various patterns of hip instability is complicated, and therefore management and outcome of these disorders are quite variable. Bellabarba et al concluded that physical therapy alone had been unsuccessful and that temporary success of a posterior capsular "plication" in one patient showed promise. Arthroscopic thermal modification of collagen in the hip capsular tissue appears to be a treatment option for patients with hip instability. The hip joint capsule is predominantly type 1 collagen, and the mechanism of tissue shrinkage through type 1 collagen alteration is well documented in the literature. Short-term results appear promising, however, more studies are required to determine the long-term efficacy of this procedure in the treatment of this challenging disorder.

Arthroscopy↗

Dynamic Lunatic fringe expression is correlated with boundaries formation in developing mouse teeth.

The formation of boundaries is a fundamental organizing principle during development. The Notch signalling pathway regulates this developmental patterning mechanism in many tissues. Recent data suggest that Notch receptors are involved in boundary determination during odontogenesis. It remains, however, uncertain if other components of the Notch pathway are also important for compartmental lineage restrictions in teeth. Here we report on the expression of the Lunatic fringe gene, which encodes a secreted signalling molecule regulating the Notch pathway, during the development of mouse teeth. Lunatic fringe is expressed in both epithelial and mesenchymal components of the developing molar. The expression pattern of Lunatic fringe in the epithelium is complementary to that of the Notch receptors. Lunatic fringe is asymmetrically expressed in the incisor epithelium during its antero-posterior rotation. This expression pattern defines the lingual comportment of the incisor epithelium whereas the labial comportment is defined by Notch2 expression.

Animals↗

How and why do the two cerebral hemispheres interact?

Research on the anatomical bases of interhemispheric interaction, including individual differences in corpus callosum (CC) anatomy, is reviewed. These anatomical findings form the basis for the discussion of two major themes. The first considers interhemispheric transfer time (IHTT) and related issues. These include varieties of IHTT and possible directional asymmetries of IHTT. Evidence suggests that pathological variations in IHTT may have cognitive consequences. The second involves conditions under which interhemispheric interaction is necessary and beneficial. The data suggest that when both hemispheres have some competence at a difficult task, there is a benefit to interhemispheric interaction. The role of the CC in the dynamic distribution of attention may be particularly relevant to this advantage. Throughout the article reference is made to individual differences and developmental changes associated with interhemispheric interaction.

Animals↗

Dietary iron intake is positively associated with hemoglobin concentration during infancy but not during the second year of life.

Iron status during infancy and early childhood reflects highly dynamic processes, which are affected by both internal and external factors. The regulation of iron metabolism seems to be subjected to developmental changes during infancy, although the exact nature of these changes and their implications are not fully understood. We wanted to explore the association between dietary iron intake and indicators of iron status, and to assess temporal changes in these variables. This was done by secondary analysis of data from a recently conducted dietary intervention trial in which healthy, term, well-nourished infants were randomly assigned to consume iron-fortified infant cereals with regular or low phytate content, or iron-fortified infant formula. Dietary iron intake from 6 to 8 mo and from 9 to 11 mo was associated with hemoglobin (Hb) concentration at 9 mo (r = 0.27, P < 0.001) and 12 mo (r = 0.21, P = 0.001), respectively, but iron intake from 12 to 18 mo was not associated with Hb at 18 mo. In contrast, iron intake from 6 to 11 mo was not associated with serum ferritin (S-Ft) at 9 or 12 mo, whereas iron intake from 12 to 17 mo was positively associated with S-Ft at 18 mo (r = 0.14, P = 0.032). These shifts in associations between dietary iron intake, and Hb and S-Ft, respectively, may be due to developmental changes in the channeling of dietary iron to erythropoiesis relative to storage, in the absence of iron deficiency anemia. These observations should be taken into consideration when evaluating iron nutritional status during infancy and early childhood.

Aging↗

Further delineation of Hennekam syndrome.

We report four children from four inbred Arab families with varying manifestations of Hennekam syndrome and additional features that have not been previously reported. These include abnormalities of the middle ear, anomalous pulmonary venous drainage, interrupted inferior vena cava, polysplenia, crossed renal ectopia, median position of the liver and multiple cavernous haemangiomas. In addition, in one case lymphoedema was absent and oedema due to hypoproteinaemia appeared at 6 years of age. Since anomalies of the veins and the consequent developmental abnormalities of the lymphatics might lead to alterations in the fluid balance of the embryo, we hypothesize that altered fluid dynamics due to defective vascular and lymphatic development might disrupt critical events in craniofacial morphogenesis resulting in Hennekam syndrome.

Abnormalities, Multiple↗

A Homolog of the Substrate Adhesion Molecule Vitronectin Occurs in Four Species of Flowering Plants.

The extracellular matrix (ECM) has been implicated in the primary developmental processes of many organisms. A family of secretory adhesive glycoproteins called substrate adhesion molecules (SAMs) is believed to confer these dynamic capabilities to the ECM in animals. In this paper, we report the existence of SAM-like genes and gene products in flowering plants. Hybridizations with a human vitronectin cDNA probe and genomic DNA from broad bean, soybean, and tomato revealed vitronectin-like sequences. Human vitronectin antibodies cross-react with a 55-kilodalton protein in leaf and root protein extracts from lily, broad bean, soybean, and tomato. In addition, immunocytochemical staining of frozen sections of lily leaf and broad bean gynoecium demonstrated that vitronectin-like proteins were localized to the ECM on the cell surface, with the most intense labeling residing in the transmitting tract of broad bean gynoecium.

Journal Article↗