Human and mouse disorders of pigmentation

Disorders of pigmentation were among the first genetic diseases ever recognized because of their visually striking clinical phenotypes, resulting from defects of pigmentary melanocytes. Recent years have seen remarkable progress in understanding these diseases, largely as a result of the systematic parallel study of human patients and inbred mice with similar phenotypes. Our understanding of disorders of pigmentation indicates that these diseases may be most usefully considered as abnormalities of melanocyte development, function, or survival.     

Effect of sulfur-containing agrochemicals on growth,yield, and protein content of soybeans (Glycine max (L.) Merr)

In this study, effect of different forms of sulfur-containing agrochemicals on growth, yield, and protein content of soybean grains have been evaluated. Three forms were used, such as powdery, solute, and pasty, in which elemental sulfur is contained in a nanostructured state. Plants treated with powdered and solute sulfur-containing agrochemicals had the highest growth and grain yield values, and the effect of applying pasty sulfur-containing agrochemicals did not differ from the control, in which there was low yield on all variants. The use of powdered and solute sulfur-containing agrochemicals increased all protein fractions in soybeans. The results show that the use of powdered and solute sulfur-containing agrochemicals is necessary to boost the yield of soy and increase the supply of proteins in the grains. A key factor in the availability of sulfur for soybean plants is the conversion of sulfur to a nanodisperse state. This study provides relevant information about sulfur-containing agrochemicals, which can promote higher seed yields and increase the content of protein in soybeans.     

Ratchet,swivel, tilt and roll: a complete description of subunit rotation in the ribosome

Protein synthesis by the ribosome requires large-scale rearrangements of the ‘small’ subunit (SSU; ∼1 MDa), including inter- and intra-subunit rotational motions. However, with nearly 2000 structures of ribosomes and ribosomal subunits now publicly available, it is exceedingly difficult to design experiments based on analysis of all known rotation states. To overcome this, we developed an approach where the orientation of each SSU head and body is described in terms of three angular coordinates (rotation, tilt and tilt direction) and a single translation. By considering the entire RCSB PDB database, we describe 1208 fully-assembled ribosome complexes and 334 isolated small subunits, which span >50 species. This reveals aspects of subunit rearrangements that are universal, and others that are organism/domain-specific. For example, we show that tilt-like rearrangements of the SSU body (i.e. ‘rolling’) are pervasive in both prokaryotic and eukaryotic (cytosolic and mitochondrial) ribosomes. As another example, domain orientations associated with frameshifting in bacteria are similar to those found in eukaryotic ribosomes. Together, this study establishes a common foundation with which structural, simulation, single-molecule and biochemical efforts can more precisely interrogate the dynamics of this prototypical molecular machine.     

Correlation of expression of Akt1 and E2F1 and their phosphorylated forms in breast cancer patients with clinicopathological parameters

Journal of Molecular Histology - Breast cancer is the leading cancer worldwide among women. Traditional clinicopathological prognostic and predictive markers need refining to improve clinical...     

The effect of thymoquinone treatment on the combined renal and pulmonary toxicity of cisplatin and diesel exhaust particles

Particulate air pollution (PAP) exposure is associated with increased morbidity and mortality, particularly in patients with renal disease. However, there are only a few studies on the interaction between PAP and renal injury, and none on agents that may ameliorate it. We studied the interaction between cisplatin (CP) nephrotoxicity and a single exposure to diesel exhaust particle (DEP) in rats 24 h before sacrifice, and assessed the effect of co-treatment with the active ingredient in Nigella Sativa seed oil, thymoquinone (TQ) thereon. Rats were injected intraperitoneally with CP (6 mg/kg) and four days later, they were exposed intratracheally to DEP (0.5 mg/kg), and were sacrificed 24 h later. Oral TQ (20 mg/kg) was given daily throughout the experimental period. CP alone caused several physiological, biochemical, and histopathological changes that included reduced growth and creatinine clearance, and raised plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 6 (IL-6) and C-reactive protein (CRP), creatinine and urea concentrations, and urinary N-acetyl-b-D-glucosaminidase (NAG) activities. It adversely affected several indices of oxidative damage in the kidneys, and induced renal tubular necrosis. Most of these actions were significantly potentiated in rats given both CP and DEP. TQ significantly abrogated many of the effects of CP and DEP, given alone and in combination. These results provide experimental evidence that subjects with renal diseases can be at higher risk from PAP, and that TQ, pending further pharmacological and toxicological studies, can be considered a useful agent in patients with renal diseases and exposed to PAP.     

<Emphasis Type="Italic">Anoxybacillus sediminis</Emphasis> sp. nov., a novel moderately thermophilic bacterium isolated from a hot spring

A Gram-stain positive, moderately thermophilic, aerobic, spore-forming and rod-shaped bacterium, designated YIM 73012^T, was isolated from a sediment sample collected from a hot spring located in Tibet, China, and was characterized by using a polyphasic taxonomy approach. The strain is oxidase positive and catalase negative. Growth occurred at 37–65 °C (optimum, 45–50 °C), at pH 6.0–8.5 (optimum, pH 7.0–7.5) and with 0.5–3.5% NaCl (optimum, 0.5–1.0%, w/v). The major fatty acids were iso-C_15:0, iso-C_16:0 and C_16:0. The major polar lipids comprised of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine and phosphatidylglycerol. The cell wall peptidoglycan contained meso-diaminopimelic acid. The respiratory quinone was MK-7. The G+C content of genomic DNA was 43.6 mol%. Phylogenetic analyses based on 16S rRNA gene sequences showed that the strain YIM 73012^T forms a distinct lineage with respect to the genus Anoxybacillus in the family Bacillaceae. Based on 16S rRNA gene sequence identities the closely related phylogenetic neighbours are Anoxybacillus caldiproteolyticus DSM 15730^T (96.7%) and Saccharococcus thermophilus DSM 4749^T (96.6%). Strain YIM 73012^T was distinguishable from the closely related reference strains by the differences in phenotypic, chemotaxonomic and genotypic characteristics, and represents a novel species of the genus Anoxybacillus, for which the name Anoxybacillus sp. nov. is proposed. The type species is Anoxybacillus sediminis sp. nov., with the type strain YIM 73012^T (=?KCTC 33884^T?=?DSM 103835^T).     

A Genomewide Screen for Generalized Vitiligo: Confirmation of AIS1 on Chromosome 1p31 and Evidence for Additional Susceptibility Loci

Generalized vitiligo is a common autoimmune disorder characterized by the development of white patches of skin and overlying hair due to loss of pigment-forming melanocytes from the involved areas. Family clustering of cases is not uncommon, in a pattern suggestive of multifactorial, polygenic inheritance, and there is strong association between vitiligo and other autoimmune diseases. To map genetic loci that confer susceptibility to generalized vitiligo and perhaps other autoimmune diseases, we performed a genomewide linkage scan in 71 white multiplex families with vitiligo from North America and the United Kingdom. Linkage was assessed by multipoint nonparametric linkage analyses. One linkage signal, AIS1, located at 1p31, met genomewide criteria for highly significant linkage (nonparametric LOD 5.56; P=.000000282), establishing its importance as a major vitiligo susceptibility locus. An additional seven signals, on chromosomes 1, 7, 8, 11, 19, and 22, met genomewide criteria for "suggestive linkage," and will thus be of particular importance for follow-up studies.     

Characterization of the interaction of Escherichia coli heat-stable enterotoxixn (STa) with its intestinal putative receptor in various age groups of mice, using flow cytometry and binding assays.

BACKGROUND AND PURPOSE: Enterotoxigenic Escherichia coli heat-stable enterotoxin (STa) is a major cause of diarrhea in young animals. Age-dependent variation in the density and affinity of the mouse enterocyte receptors specific for STa was investigated. METHODS: Four age groups (2-day-, 1- and 2-week-, and 2-month-old) of Swiss Webster mice were studied (8 to 10 mice/group). Flow cytometry and radiolabeled STa (125I-STa) assays were used as reliable quantitative measures for characterization of STa-enterocyte receptor interaction. RESULTS AND CONCLUSIONS: Interaction of STa with its putative receptor was stronger for enterocytes of 2-day-old mice. Scatchard analysis of 125I-STa-receptor interaction suggested that STa-receptors exist at higher numbers on enterocytes from 2-day-old (7.2 nmol/mg) than older (0.30, 0.36, and 0.40 nmol/mg for 1-week-, 2-week-, and 2-month-old mice, respectively). Additionally, receptors from 2-day-old mice had greater affinity for STa (Kd = 75 nM) than did receptors from older mice (Kd = 125, 1,430, and 1,111 nM for 1-week-, 2-week-, and 2-month-old mice, respectively). Density of STa receptors on enterocytes and their affinity to STa may determine extent of binding and severity of the secretory response, and may explain the high susceptibility of newborn animals and human infants to STa-mediated diarrhea.     

Influence of kaurenol on basal, LH- and forskolin-stimulated progesterone and cAMP production in avian granulosa cells

The effects of kaurenol, a diterpene alcohol, were evaluated on progesterone and cyclic AMP (cAMP) production in freshly dispersed avian granulosa cells. Kaurenol (50 microM) alone caused a fourfold increase in progesterone synthesis without a measurable influence on cAMP levels. When granulosa cells were challenged with near-maximally stimulating concentrations of LH (50 ng/ml) or forskolin (10 microM), kaurenol (10-100 microM) dose-dependently suppressed steroidogenesis. Similarly, cAMP production in response to LH and forskolin stimulation was also inhibited. When progesterone synthesis was stimulated by the addition of pregnenolone or 25-hydroxycholesterol substrates to the culture medium, the typical dose response to the latter precursor, but not to pregnenolone, was abolished by kaurenol. Whereas the mechanism of kaurenol's stimulatory effect on basal steroidogenesis remains unknown, it is suggested that its inhibitory action on LH- and forskolin-promoted progesterone production may be due to the inhibition of the adenylate cyclase cAMP effector system as well as to the impairment of the action of the mitochondrial cholesterol side chain cleavage enzyme system.     

Evidence for two distinct potassium channels in avian granulosa cells

Single-channel potassium currents were recorded in avian granulosa cells using the patch-clamp technique. Two types of channel were observed. The smaller of the two channels, gK1, had a conductance of 15 to 30 picosiemens (pS) and was voltage- and calcium-independent. Its null-current potential was -50 mV in the cell-attached recording mode. The other channel, gK2, was infrequently observed in the cell-attached configuration. Its conductance was between 160 and 195 pS. It could be activated by calcium on the cytoplasmic side of the membrane patch in the inside-out configuration. It was also voltage-dependent. These results suggest that fast transmembrane potassium movements may be involved in the membrane voltage regulation of granulosa cells, which in turn may play an important role in the modulation of steroidogenesis and other metabolic activities.