ATPase Activity in Flagella from Euglena gracilis. Localization of the Enzyme and Effects of Detergents*

SYNOPSIS. The biochemical effects of some detergents on the ATPase activity of isolated flagella from Euglena gracilis are related to morphologic obliterations induced by those detergents. Enzymic activity can be localized by electron microscopy along the microtubules and also on the paraflagellar rod. The nonionic detergent digitonin solubilizes the enzyme linked to dyneinic arms, whereas the activity linked to residual structures appears enhanced. These results support the hypothesis that the paraflagellar rod may be a structure actively related to the motility of this type of flagellum.     

Protection against oxidative stress by vitamin D in cone cells

Photoreceptor degeneration (PD) refers to a group of heterogeneous outer retinal dystrophies characterized by the death of photoreceptors. Both oxidative stress and inflammation are involved in the pathogenesis of PD. We investigate whether vitamin D has a potential for the treatment of PD by evaluating the anti‐oxidative stress and anti‐inflammatory properties of the active form of vitamin D₃, 1,α, 25‐dihydroxyvitamin D₃, in a mouse cone cell line, 661W. Mouse cone cells were treated with H₂O₂ or a mixture of H₂O₂ and vitamin D; cell viability was determined. The production of reactive oxygen species (ROS) in treated and untreated cells was measured. The expression of key anti‐oxidative stress and inflammatory genes in treated and untreated cells was determined. Treatment with vitamin D significantly increased cell viability and decreased ROS production in 661W cells under oxidative stress induced by H₂O₂. H₂O₂ treatment in 661W cells can significantly down‐regulate the expression of antioxidant genes and up‐regulate the expression of neurotoxic cytokines. Vitamin D treatment significantly reversed these effects and restored the expression of antioxidant genes. Vitamin D treatment also can block H₂O₂ induced oxidative damages. The data suggested that vitamin D may offer a therapeutic potential for patients with PD.     

The evolutionary geometry of human anatomy: Discovering our inner fly

The human body is one still frame in a very long evolutionary movie. Anthropologists focus on the last few scenes, whereas geneticists try to trace the screenplay back as far as possible. Despite their divergent time scales (millions versus billions of years), both disciplines share a reliance on a third field of study whose scope spans only a matter of days to months, depending on the organism. Embryology is crucial for understanding both the pliability of anatomy and the modularity of gene circuitry. The relevance of human embryology to anthropology is obvious. What is not so obvious is the notion that equally useful clues about human anatomy can be gleaned by studying the development of the fruit fly, an animal as different from us structurally as it is distant from us evolutionarily. The underlying kinship between ourselves and flies has only become apparent recently, thanks to revelations from the nascent field of evolutionary developmental biology, or evo‐devo. All bilaterally symmetric animals, it turns out, share a common matrix of body axes, a common lexicon of intercellular signals, and a common arsenal of genetic gadgetry that evolution has tweaked in different ways in different lineages to produce a dazzling spectrum of shapes and patterns. Anthropologists can exploit this deep commonality to search our genome more profitably for the mutations that steered us so far astray from our fellow apes.     

Cytokine gene polymorphisms are associated with risk of urinary bladder cancer and recurrence after BCG immunotherapy

The association of interleukin-1β (IL-1B) -511C?>?T and IL-1 receptor antagonist (IL-1RN) VNTR, transforming growth factor-β (TGF-B1) +28C?>?T and interferon-γ (IFN-G)?+?874T>A polymorphisms with bladder cancer (CaB) susceptibility and risk of recurrence in Bacillus Calmette–Guérin (BCG)-treated patients was analyzed in 287 controls and 213 CaB patients (73 BCG treated). Increased risk was observed with the IL-1RN*2 allele (odds ratio (OR) 5.01) and the IFN-G +874 A allele (OR 1.78). TGF-B TT and IFN-G +874 A carriers were associated with reduced (hazard ratio (HR) 0.37) and enhanced (HR 2.24) risk of recurrence after BCG immunotherapy, respectively. The study suggests that cytokine gene variants may modulate CaB susceptibility and risk of recurrence after BCG immunotherapy.     

Some new indole–coumarin hybrids; Synthesis,anticancer and Bcl-2 docking studies

Hybrid molecules have attracted attention for their improved biological activity, selectivity and lesser side effects profile, distinct from their individual components. In the quest for novel anticancer drug entities, three series of indole–coumarin hybrids – 3-(1-benzyl-1H-indol-2-yl)-2H-chromen-2-ones, 2-(2-oxo-2H-chromen-3-yl)-1H-indole-3-carbaldehydes and 2-(2-oxo-2H-chromen-3-yl)-1H-indole-3-carboxylic acids were synthesized. All the synthesized compounds were characterized by spectral techniques like IR, ¹H NMR, ¹³C NMR, mass spectrometry and elemental analysis. In silico docking studies of synthesized molecules with apoptosis related gene Bcl-2 that is recognized to play an important role in tumerogenesis were carried out. Dose-dependent cytotoxic effect of the compounds in human breast adenocarcinoma (MCF-7) and normal cell lines were assessed using MTT assay and compared with that of the standard marketed drug, Vincristine. Compound 4c had a highly lipophilic bromine substituent capable of forming halogen bond and was identified as a potent molecule both in docking as well as cytotoxicity studies. Flow cytometric cell cycle analysis of 4c exhibited apoptotic mode of cell death due to cell cycle arrest in G2/M phase. Structure activity relationship of these hybrid molecules was also studied to determine the effect of steric and electronic properties of the substituents on cell viability.     

7,9-Diaryl-1,6,8-trioxaspiro[4.5]dec-3-en-2-ones: Readily accessible and highly potent anticancer compounds

7,9-Diaryl-1,6,8-trioxaspiro[4.5]dec-3-en-2-ones are a recently described group of spirocyclic butenolides that can be generated rapidly and as a single diastereomer through a cascade process between γ-hydroxybutenolides and aromatic aldehydes. The following outlines our findings that these spirocycles are potently cytotoxic and have a dramatic structure–function profile that provides excellent insight into the structural features required for this potency.     

Twelve-Hour Night Shifts of Healthcare Workers: A Risk to the Patients?

We assessed the impact of 12h fixed night shift (19:00–07:00h) work, followed by 36h of off-time, on the sleep–wake cycle, sleep duration, self-perceived sleep quality, and work-time alertness on a group composed of 5 registered and 15 practical nurses. Wrist actigraphy (Ambulatory Monitoring, Inc.), with data analysis by the Cole-Kripke algorithm, was applied to determine sleep/wake episodes and their duration. The sleep episodes were divided into six categories: sleep during the night shift (x¯=208.6; SD±90.6mins), sleep after the night shift (x¯=138.7; SD±79.6min), sleep during the first night after the night work (x¯=318.5; SD±134.6min), sleep before the night work (x¯=104.3; SD±44.1min), diurnal sleep during the rest day (x¯=70.5; SD±43.0min), and nocturnal sleep during the rest day (x¯=310.4; SD±188.9mins). A significant difference (p<.0001; T-test for dependent samples) was detected between the perceived quality of sleep of the three diurnal sleep categories compared to the three nocturnal sleep categories. Even thought the nurses slept (napped) during the night shift, their self-perceived alertness systematically decreased during it. Statistically significant differences were documented by one-way ANOVA (F=40.534 p<.0001) among the alertness measurements done during the night shift. In particular, there was significant difference in the level of perceived alertness (p<.0001) between the 7^th and 10^thh of the 12h night shift. These findings of decreased alertness during the terminal hours of the night shift are of concern, since they suggest risk of comprised patient care.     

Synthesis of arylated coumarins by Suzuki–Miyaura cross-coupling. Reactions and anti-HIV activity

Arylated coumarins were prepared by site-selective Suzuki–Miyaura cross-coupling reaction of the bis(triflate) of 4-methyl-6,7-dihydroxycoumarin. Triarylated coumarins were prepared by Suzuki–Miyaura cross-coupling reactions of 3-bromo-4-methyl-2-oxo-2H-chromene-6,7-diylbis(trifluoromethanesulfonate). The in vitro anti-HIV activity of the products was investigated. Two lead structures with considerable activities were identified.