Intrafamilial and interfamilial heterogeneity of PINK1-associated Parkinson's disease in Sudan.

PINK1 is the second most predominant gene associated with autosomal recessive Parkinson's disease. Homozygous mutations in this gene are associated with an early onset of symptoms. Bradykinesia, tremors, and rigidity are common features, while dystonia, motor fluctuation, and non-motor symptoms occur in a lower percentage of cases and usually respond well to levodopa. We investigated 14 individuals with parkinsonism and eleven symptom-free siblings from three consanguineous Sudanese families, two of them multigenerational, using a custom gene panel screening 34 genes, 27 risk variants, and 8 candidate genes associated with parkinsonism. We found a known pathogenic nonsense PINK1 variant (NM_032409.3:c.1366C>T; p.(Gln456*)), a novel pathogenic single base duplication (NM_032409.3:c.1597dup; p.(Gln533Profs*29)), and another novel pathogenic insertion (NM_032409.3:c.1448_1449ins[1429_1443; TTGAG]; p.(Arg483Serfs*7)). All variants were homozygous and co-segregated in all affected family members. We also identified intrafamilial and interfamilial phenotypic heterogeneity associated with PINK1 mutations in these Sudanese cases, possibly reflecting the nature of the Sudanese population that has a large effective population size, which suggests a higher possibility of novel findings in monogenic and polygenic diseases in Sudan.

Methylation of alpha-synuclein in a Sudanese cohort.

BACKGROUND: Several studies suggested a significant role of epigenetic changes, including alterations in miRNA, histone modifications, and DNA methylation of α-synuclein (SNCA) in Parkinson's disease (PD) pathogenicity. As of yet, only very few studies have been carried out in this field in Africa and none in Sudan. MATERIALS AND METHODS: We collected DNA from 172 Sudanese individuals (90 cases, 82 controls) who donated saliva for DNA extraction (mean age of onset: 40.6 ± 22.4 years). A family history of PD was evident in 64 patients. DNA preparation and bisulfite sequencing of SNCAintron1 was performed as described earlier. RESULTS: Of the fourteen analyzed CpGs of SNCAintron1, CpGs 16-23 were hypomethylated in PD (P-value ranged from 0.023 to 0.003). P-values improved, when sporadic cases were excluded from the analysis. CONCLUSION: We identified the presence of a specific pattern of DNA methylation in a young Sudanese cohort of familial PD, which confirms the importance of the methylation of SNCAintron1 for PD. This phenomenon appears to be independent of ethnicity, the impact of environmental factors, drug history, or familial clustering.

Hydrogen peroxide mediates the cell growth and transformation caused by the mitogenic oxidase Nox1.

Nox1, a homologue of gp91phox, the catalytic moiety of the superoxide (O(2)(-))-generating NADPH oxidase of phagocytes, causes increased O(2)(-) generation, increased mitotic rate, cell transformation, and tumorigenicity when expressed in NIH 3T3 fibroblasts. This study explores the role of reactive oxygen species (ROS) in regulating cell growth and transformation by Nox1. H(2)O(2) concentration increased approximately 10-fold in Nox1-expressing cells, compared with <2-fold increase in O(2)(-). When human catalase was expressed in Nox1-expressing cells, H(2)O(2) concentration decreased, and the cells reverted to a normal appearance, the growth rate normalized, and cells no longer produced tumors in athymic mice. A large number of genes, including many related to cell cycle, growth, and cancer (but unrelated to oxidative stress), were expressed in Nox1-expressing cells, and more than 60% of these returned to normal levels on coexpression of catalase. Thus, H(2)O(2) in low concentrations functions as an intracellular signal that triggers a genetic program related to cell growth.

The shuttle glow phenomenon.

Spacecraft in low earth orbit exhibit an unusual phenomenon: Surfaces facing the atmospheric wind produce a bright orange glow. This phenomenon was first noticed on the space shuttle but has since been verified as occurring on all spacecraft. The intensity of the glow depends on atmospheric density, on the angle between the velocity vector and the spacecraft surface, and on the temperature of the surface. This review summarizes the observations as well as the current explanation for the glow, namely its being due to NO2* formed in surface-aided recombination between O and NO. Laboratory measurements and surface studies related to the phenomenon are briefly discussed.

[Chronic end-stage kidney failure in Mexico]. / Algunas reflexiones sobre la insuficiencia renal crónica terminal en México.

Chronic renal failure is an expanding and complex problem in Mexico. This work analyzes its current situation and finds a clear imbalance between supply and demand for specialized services, that favors the latter. To explain said imbalance, it invokes four factors: the recent innovation in nephrology and parallel disciplines; educational deficit of medical schools; high costs of rehabilitation of the uremic patient, and the absence of specifically designed mechanisms for financing the treatment of this disease.

Panchromatic spectrograph with supporting monochromatic imagers.

The Arizona Imager/Spectrograph is a set of imaging spectrographs and two-dimensional imagers for space flight. Nine nearly identical spectrographs record wavelengths from 114 to 1090 nm with a resolution of 0.5-1.3 nm. The spatial resolution along the slit is electronically selectable and can reach 192 elements. Twelve passband imagers cover wavelengths in the 160-900-nm range and have fields of view from 2 degrees to 21 degrees . The spectrographs and imagers rely on intensified CCD detectors to achieve substantial capability in an instrument of minimum mass and size. By use of innovative coupling techniques only two CCD's are required to record images from 12 imagers, and single CCD's record spectra from pairs of spectrographs. The fields of view of the spectrographs and imagers are coaligned, and all spectra and images can be exposed simultaneously. A scan platform can rotate the sensor head about two orthogonal axes. The Arizona imager/spectrograph is designed for investigations of the interaction between the Space Shttle and its environment. It is scheduled for flight on a Shuttle subsatellite.

Intercalation and the cellular origin of supernumerary limbs in Xenopus.

The hypothesis that a specialized polarizing zone controls the pattern of the anterior-posterior axis during limb development in Xenopus has been tested by analysing the cellular contribution to supernumerary limbs. Supernumerary limbs were generated by grafting hindlimb buds contralaterally between X. borealis and X. laevis to appose anterior and posterior limb tissues. Cells derived from these two species of Xenopus are readily identified by staining with quinacrine. The analysis of cellular contribution showed that supernumerary limbs consist of approximately half anterior-derived (57%) and half posterior-derived (43%) cells. These data are not consistent with the polarizing zone theory but are consistent with the hypothesis that both supernumerary limbs and normally developing limbs arise from intercalary interactions between limb bud cells with different positional values.

[Hormone profile of the essential hypertension patient with ischemic cardiopathy. I. Renin, angiotensin and aldosterone]. / El perfil hormonal del hipertenso esencial con cardiopatía isquémica. (I) Renina, angiotensina y aldosterona.

To evaluate the characteristics that the renin and aldosterone profile could present in essential hypertensive patients complicated with ischemic heart disease, and as a contribution to the knowledge of the roll that these hormones could have as possible "risk factors" of coronary heart disease, sixty male patients were studied. These were divided in three groups: group I, formed by 15 essential hypertensive patients with objectively demonstrated ischemic heart disease; group II integrated by 15 essential hypertensives with no ischemic heart disease and group III with 30 normal volunteers. Serum levels of plasma renin activity (PRA) and aldosterone determined by radioimmunoassay, and of urinary sodium excretion were measured in all the patients. The distribution of cases with high, normal and low renin and aldosterone were similar in group I and in group II. It was interesting to find that the four patients of group I who were non-smokers, presented the lower renin levels (from 0.36 to 2.8 ng/ml/h). The relation between PRA and the number of occluded coronary arteries revealed an increased number of patients and affected arteries in the subgroup with renin levels above 5 ng/ml/h in comparison with the subgroup with PRA from 0 to 5, although the difference was not statistically significant. By our study, we cannot conclude that the PRA and aldosterone behave in a different fashion in essential hypertensives from those complicated with ischemic heart disease.

Quantitative counterimmunoelectrophoresis for urinary fibrinogen-related antigens.

A quantitative procedure for urinary fibrinogen-related antigens, applying counterimmunoelectrophoresis to serial dilutions of concentrated samples against standards of known fibrinogen concentrations, is described. It is fast, convenient, sensitive enough (r = 0.8729, p less than 0.001), and can be easily incorporated into routine laboratory work.