Progression of central nervous system disease from pediatric to young adulthood in sickle cell anemia

Silent cerebral infarcts and arteriopathy are common and progressive in individuals with sickle cell anemia. However, most data describing brain lesions in sickle cell anemia are cross-sectional or derive from pediatric cohorts with short follow-up. We investigated the progression of silent cerebral infarct and cerebral vessel stenosis on brain MRI and MRA, respectively, by describing the incidence of new or worsening lesions over a period of up to 25 years among young adults with sickle cell anemia and explored risk factors for progression. Forty-four adults with sickle cell anemia (HbSS or HbSβ⁰thalassemia), exposed to chronic transfusions (n = 12) or hydroxyurea (n = 32), median age 19.2 years (range 18.0–31.5), received a screening brain MRI/MRA and their results were compared with a clinical exam performed during childhood and adolescence. We used exact log-rank test to compare MRI and MRA progression among any two groups. The hazard ratio (HR) and 95% confidence interval (CI) were calculated from Cox regression analyses. Progression of MRI and MRA occurred in 12 (27%) and 4 (9%) young adults, respectively, relative to their pediatric exams. MRI progression risk was high among participants with abnormal pediatric exams (HR: 11.6, 95% CI: 2.5–54.7) and conditional or abnormal transcranial Doppler ultrasound velocities (HR: 3.9, 95% CI: 1.0–15.1). Among individuals treated with hydroxyurea, high fetal hemoglobin measured in childhood was associated with lower hazard of MRI progression (HR: 0.86, 95% CI: 0.76–0.98). MRA progression occurred more frequently among those with prior stroke (HR: 8.6, 95% CI: 1.2–64), abnormal pediatric exam (P = 0.00084), and elevated transcranial Doppler ultrasound velocities (P = 0.004). Brain MRI/MRA imaging in pediatrics can identify high-risk patients for CNS disease progression in young adulthood, prompting consideration for early aggressive treatments.     

Ultrastructural Effects of Water Stress on Chloroplast Development in Jack Bean (Canavalia ensiformis [L.] DC)

An ultrastructural study has been made to determine to what degree chloroplast differentiation is retarded in leaves of young jack bean (Canavalia ensiformis [L.] DC.) seedlings when they are subjected to mild water stress. Rapid chloroplast differentiation occurred when etiolated seedlings were allowed to green at relative humidities above 85% but not at a relative humidity of 25%. Response to a drop in humidity was rapid. Germination and early development in the dark occurred at 100% relative humidity. At the time of exposure to light, the etioplasts contained well formed prolamellar bodies. Under high relative humidity conditions, transformation of the prolamellar body was well advanced within 2 hours. Under low relative humidity conditions, however, prolamellar body differentiation was extremely retarded for more than 24 hours following the beginning of illumination.     

NMClab, a model to assess the contributions of muscle visco-elasticity and afferent feedback to joint dynamics

The dynamic behavior of a neuromusculoskeletal system results from the complex mechanical interaction between muscle visco-elasticity resulting from (co-)contraction and afferent feedback from muscle spindles and Golgi tendon organs. As a result of the multiple interactions the individual effect of each of the structures to the overall dynamics is hard to recognize, if not impossible. Here a neuromuscular control (NMC) model is developed to analyze the functional contribution of the various physiological structures on the mechanical behavior of a limb. The dynamics of a joint are presented in admittances, i.e. the dynamic relation between input force (or torque) and the output displacement, which can be represented by either frequency or impulse response functions. With the model it can be shown that afferent feedback reduces, while muscle visco-elasticity increases, the stability margins. This implicates that there is a delicate balance between muscle co-contraction and afferent feedback, which depends on the joint specific physiological properties. The main application of the model is educational; it is implemented in a graphical user interface allowing users to explore the role of the various physiological structures on joint dynamics. Other applications of the model are more experimental, e.g. to elucidate experimentally measured admittances and to compare the quantified parameter values with the theoretically optimal ones. It is concluded that the NMC model is a useful and intuitive tool to investigate human motor control, in a theoretical as well as an experimental way.     

Childbearing in crisis: war, migration and fertility in Angola

This study examines the short- and long-term effects of war-induced and war-unrelated migration on fertility outcomes using data from two peri-urban municipalities of Greater Luanda in Angola. In the short term, results from multi-level discrete-time logistic regression models indicate that net of other factors, war-unrelated migration is associated with a lower probability of birth than war-induced migration in a given year. Similar results are obtained when the effects of migration are lagged by a year. At the same time, the effects of war-triggered migration do not differ significantly from those of not migrating in a given year but are statistically significant when the effects of migration are lagged by a year. In the long term, the effects of migration experience on cumulative fertility are negligible and not statistically significant net of demographic and socioeconomic variables. Interpretations of the results are offered in the context of Angola and their broader implications are reflected on.     

Use of 3-hydroxyphenylacetylene for activity-dependent, fluorescent labeling of bacteria that degrade toluene via 3-methylcatechol

3-hydroxyphenylacetylene (3-HPA) served as a novel, activity-dependent, fluorogenic and chromogenic probe for bacterial enzymes known to degrade toluene via meta ring fission of the intermediate, 3-methylcatechol. By this direct physiological analysis, cells grown with an aromatic substrate to induce the synthesis of toluene-degrading enzymes were fluorescently labeled.     

Integration of Sensory Force Feedback Is Disturbed in CRPS-Related Dystonia

Complex regional pain syndrome (CRPS) is characterized by pain and disturbed blood flow, temperature regulation and motor control. Approximately 25% of cases develop fixed dystonia. The origin of this movement disorder is poorly understood, although recent insights suggest involvement of disturbed force feedback. Assessment of sensorimotor integration may provide insight into the pathophysiology of fixed dystonia. Sensory weighting is the process of integrating and weighting sensory feedback channels in the central nervous system to improve the state estimate. It was hypothesized that patients with CRPS-related dystonia bias sensory weighting of force and position toward position due to the unreliability of force feedback. The current study provides experimental evidence for dysfunctional sensory integration in fixed dystonia, showing that CRPS-patients with fixed dystonia weight force and position feedback differently than controls do. The study shows reduced force feedback weights in CRPS-patients with fixed dystonia, making it the first to demonstrate disturbed integration of force feedback in fixed dystonia, an important step towards understanding the pathophysiology of fixed dystonia.     

Environmental Variability, Historical Contingency, and the Structure of Regional Fish and Macroinvertebrate Faunas in Ouachita Mountain Stream Systems

In 1990–1992, the United States Forest Service sampled six hydrologically variable streams paired in three different drainage basins in the Ouachita Mountains, Arkansas, U.S.A. Fishes, macroinvertebrates, and stream environmental variables were quantified for each stream. We used these data to examine the relationship between regional faunas (based on taxonomy and trophic affiliation of fishes and macroinvertebrates) and measured environmental variables. Because fishes are constrained to their historically defined drainage basins and many insect taxa are able to cross basin barriers, we anticipated that both groups would respond differently to environmental variability. Fishes were influenced more by environmental variability that was unique to their historical drainage basins, but macroinvertebrates were associated more strongly with environmental variability that was independent of drainage basins. Thus, the individual drainage basins represented a historical constraint on regional patterns of fish assembly. For both fishes and macroinvertebrates, groupings based on taxonomy and trophic affiliation showed a similar response to environmental variability and there was a high degree of association between taxonomic and trophic correlation matrices. Thus, trophic group structure was highly dependent on the taxonomic make-up of a given assemblage. At the basin-level, fish and macroinvertebrate taxa were associated more strongly with environmental variability than the trophic groups, and these results have implications for basin-level studies that use trophic groupings as a metric to assess ecological patterns. Trophic categories may not be a useful ecological measure for studies at large spatial scales.     

Natural antioxidants attenuate mycolactone toxicity to RAW 264.7 macrophages

Mycobacterium ulcerans produces a macrolide exotoxin, mycolactone which suppresses immune cells activity, is toxic to most cells and the key virulence factor in the pathogenesis of Buruli ulcer disease. Mycolactone is reported to mediate the production of reactive oxygen species in keratinocytes; cells that play critical role in wound healing. Increased levels of reactive oxygen species have been shown to disrupt the well-ordered process of wound repair; hence, the function of wound-healing cells such as macrophages, keratinocytes, and fibroblast could be impaired in the presence of the reactive oxygen species mediator, mycolactone. To ensure regeneration of tissues in chronic ulcers, with proper and timely healing of the wounds, natural antioxidants that can combat the effects of induced reactive oxygen species in wound-healing cells ought to be investigated. Reactive oxygen species activity was determined in mycolactone-treated RAW 264.7 macrophages and the scavenging ability of the antioxidants (ascorbic acid, gallic acid, and green tea kombucha) against mycolactone-induced reactive oxygen species (superoxide anions) was assessed using fluorescein probe (DCF-DA) and nitroblue tetrazolium dye. Cytotoxicity of the antioxidants, mycolactone, and the protective effect of the antioxidants on the cells upon treatment with mycolactone were determined using the Alamar blue assay. The expression levels of endogenous antioxidant enzyme genes (superoxide dismutase, catalase, and glutathione peroxidase) in response to mycolactone-mediated reactive oxygen species were determined using RT-qPCR. Mycolactone induced the production of reactive oxygen species in RAW 264.7 macrophages, and the resulting superoxide anions were scavenged by some of the antioxidants. The selected endogenous antioxidant enzyme genes in the macrophages were upregulated in the presence of the antioxidants and mycolactone. The exogenously supplied ascorbic acid and green tea kombucha offered moderate protection to the macrophages against the toxicity of mycolactone. We conclude that the results provide insights into alternate and adjunct therapeutic approaches in Buruli ulcer treatment, which could significantly attenuate the toxicity of the pathogenic factor; mycolactone.     

Levels of polyphenol oxidase activity in leaves of Milicia seedlings is indicative of the resistance to Phytolyma lata-induced gall disease

1. Phytolyma lata-induced galling has remained one of the foremost challenges limiting the regeneration of Milicia species in nurseries and degraded forests in West Africa. Although planting of Milicia progenies resistant to Phytolyma attack has been identified as an opportunity for long-term control of the pest, the absence of biomarkers for early detection of resistance has limited the selection of resistant seedlings for planting.
2. We compared phenolic metabolites and oxidative enzymes in resistant and susceptible Milicia progenies with the aim of identifying potential biomarkers for resistance to Phytolyma-induced galling in seedlings.
3. Levels of total phenolics and ortho-dihydroxyphenolics did not significantly differ between the susceptible and resistant saplings or among seedlings. Similarly, peroxidase activity did not differ among sapling progenies or among seedlings. Thus, no clearly defined role could be ascribed to phenolics and peroxidase in resistance of Milicia species to P. lata-induced galling. However, polyphenol oxidase (PPO) activity was over two-fold higher in the resistant than the tolerant or susceptible progenies, suggesting that higher levels of PPO activity corresponded with an increased level of resistance to galling.
4. With further validation, PPO activity in leaves of Milicia seedlings can be used as a biomarker of resistance to Phytolyma-induced galling.