Effects of lindane on the glucose metabolism in rat brain cortex cells.

The influence of 0.5 mM gamma-hexachlorocyclohexane (gamma-HCH, lindane) on glucose transport has been investigated using the analog 3-O-methyl-D-(U-14C)glucose. The glucose uptake was lineal for at least 10 sec. Preincubation of dissociated brain cortex cells with lindane decreased the transport of glucose with respect to the controls. The treatment of brain cortex cells with other organochlorine compounds indicated that the alpha-, delta-HCH isomers and dieldrin reproduced the same inhibitory pattern, while beta-HCH and endrin were inactive. The total radioactivity incorporated into CO2 from (U-14C) glucose in the cerebral cortex is also inhibited by lindane in a time dependent manner.     

Phenomenon of Quantum Entanglement in a System Composed of Two Minimal Protocells

The quantum mechanical self-assembly of two separate photoactive supramolecular systems with different photosynthetic centers was investigated by means of density functional theory methods. Quantum entangled energy transitions from one subsystem to the other and the assembly of logically controlled artificial minimal protocells were modeled. The systems studied were based on different photoactive sensitizer molecules covalently bonded to a non-canonical oxo-guanine::cytosine supramolecule with the precursor of a fatty acid (pFA) molecule attached via Van der Waals forces, all surrounded by water molecules. The electron correlation interactions responsible for the weak hydrogen and Van der Waals chemical bonds increased due to the addition of polar water solvent molecules. The distances between the separated sensitizer, nucleotide, pFA, and water molecules are comparable to Van der Waals and hydrogen bonding radii. As a result, the overall system becomes compressed, resulting in photo-excited electron tunneling from the sensitizer (bis(4-diphenylamine-2-phenyl)-squarine or 1,4-bis(N,N-dimethylamino)naphthalene) to the pFA molecules. Absorption spectra as well as electron transfer trajectories associated with the different excited states were calculated using time dependent density functional theory methods. The results allow separation of the quantum entangled photosynthetic transitions within the same minimal protocell and with the neighboring minimal protocell. The transferred electron is used to cleave a “waste” organic molecule resulting in the formation of the desired product. A two variable, quantum entangled AND logic gate was proposed, consisting of two input photoactive sensitizer molecules and one output (pFA molecule). It is proposed that a similar process might be applied for the destruction of tumor cancer cells or to yield building blocks in artificial cells.     

Effect of Training and Match Loads on Hamstring Passive Stiffness in Professional Soccer Players

Objective:the purpose of this study was to identify differences in hamstring passive stiffness between the pre-season and in-season periods.Methods:Hamstring strength and passive stiffness were measured in professional male soccer players before and after the pre-season (4 weeks), and after the in-season (6 weeks) periods using an isokinetic dynamometer. Muscle passive stiffness was determined from the slope of the passive torque–angle relationship. External loads (acceleration and jumps) were monitored by GPS and internal loads by questionnaire.Results:Hamstring passive stiffness increased after 10 weeks of training and matches, without changes in passive peak torque and range of motion. The hamstring passive stiffness modifications were associated with the volume and intensity of accelerations and jumps. The individual data analysis also provided some support for the suppression of the biomechanical adaptation in the subjects with relatively large external load.Conclusions:Regular training and match workouts increase hamstring passive stiffness in professional soccer players but the adaptation of muscle-tendon unit passive elements might not occur if players experience excessive mechanical stress.     

High Incidence of Tuberculosis,Low Sensitivity of Current Diagnostic Scheme and Prolonged Culture Positivity in Four Colombian Prisons. A Cohort Study

Objective

To determine the incidence of pulmonary tuberculosis (TB) in inmates, factors associated with TB, and the time to sputum smear and culture conversion during TB treatment.

Methods

Prospective cohort study. All prisoners with respiratory symptoms (RS) of any duration were evaluated. After participants signed consent forms, we collected three spontaneous sputum samples on consecutive days. We performed auramine-rhodamine staining, culturing with the thin-layer agar method, Löwestein-Jensen medium and MGIT, susceptibility testing for first-line drugs; and HIV testing. TB cases were followed, and the times to smear and culture conversion to negative were evaluated.

Results

Of 9,507 prisoners held in four prisons between April/30/2010 and April/30/2012, among them 4,463 were screened, 1,305 were evaluated for TB because of the lower RS of any duration, and 72 were diagnosed with TB. The annual incidence was 505 cases/100,000 prisoners. Among TB cases, the median age was 30 years, 25% had <15 days of cough, 12.5% had a history of prior TB, and 40.3% had prior contact with a TB case. TB-HIV coinfection was diagnosed in three cases. History of prior TB, contact with a TB case, and being underweight were risk factors associated with TB. Overweight was a protective factor. Almost a quarter of TB cases were detected only by culture; three cases were isoniazid resistant, and two resistant to streptomycin. The median times to culture conversion was 59 days, and smear conversion was 33.

Conclusions

The TB incidence in prisons is 20 times higher than in the general Colombian population. TB should be considered in inmates with lower RS of any duration. Our data demonstrate that patients receiving adequate anti-TB treatment remain infectious for prolonged periods. These findings suggest that current recommendations regarding isolation of prisoners with TB should be reconsidered, and suggest the need for mycobacterial cultures during follow-up.     

Novel series of pyrrolotriazine analogs as highly potent pan-Aurora kinase inhibitors

The synthesis and SAR for a novel series of pyrrolotriazines as pan-Aurora kinase inhibitors are described. Optimization of the cyclopropane carboxamide terminus of lead compound 1 resulted in analogs with high cellular activity and improved rat PK profiles. Notably, compound 17l demonstrated tumor growth inhibition in a mouse xenograft model.     

Crassulacean acid metabolism enhances underwater photosynthesis and diminishes photorespiration in the aquatic plant Isoetes australis

? Underwater photosynthesis by aquatic plants is often limited by low availability of CO(2), and photorespiration can be high. Some aquatic plants utilize crassulacean acid metabolism (CAM) photosynthesis. The benefits of CAM for increased underwater photosynthesis and suppression of photorespiration were evaluated for Isoetes australis, a submerged plant that inhabits shallow temporary rock pools. ? Leaves high or low in malate were evaluated for underwater net photosynthesis and apparent photorespiration at a range of CO(2) and O(2) concentrations. ? CAM activity was indicated by 9.7-fold higher leaf malate at dawn, compared with at dusk, and also by changes in the titratable acidity (μmol H(+) equivalents) of leaves. Leaves high in malate showed not only higher underwater net photosynthesis at low external CO(2) concentrations but also lower apparent photorespiration. Suppression by CAM of apparent photorespiration was evident at a range of O(2) concentrations, including values below air equilibrium. At a high O(2) concentration of 2.2-fold the atmospheric equilibrium concentration, net photosynthesis was reduced substantially and, although it remained positive in leaves containing high malate concentrations, it became negative in those low in malate. ? CAM in aquatic plants enables higher rates of underwater net photosynthesis over large O(2) and CO(2) concentration ranges in floodwaters, via increased CO(2) fixation and suppression of photorespiration.     

Requirement of left-handed glycine residue for high stability of the Tk-subtilisin propeptide as revealed by mutational and crystallographic analyses

Tk-subtilisin [the mature domain of Pro-Tk-subtilisin in active form (Gly70-Gly398)] from the hyperthermophilic archaeon Thermococcus kodakaraensis is matured from Pro-Tk-subtilisin [a subtilisin homologue from T. kodakaraensis in pro form (Gly1-Gly398)] upon autoprocessing and degradation of propeptide. Pro-Tk-subtilisin is characterized by extremely slow maturation at mild temperatures, but this maturation rate is greatly increased by a single Gly56 → Ser mutation in the propeptide region. To analyze the role of Gly56, which assumes a left-handed conformation, Pro-Tk-subtilisin variants with complete amino acid substitutions at Gly56 were constructed. A comparison of their halo-forming activities suggests that all variants, except for Pro-G56W [Pro-G56X, Pro-Tk-subtilisin with Gly56 → X mutation (X = any amino acid)], mature faster than WT. Pro-G56W and Pro-G56E with the lowest and highest maturation rates, respectively, among 19 variants, as well as WT and Pro-G56S, were overproduced, purified, and characterized. SDS-PAGE analyses and Tk-subtilisin activity assay indicated that their maturation rates increased in the order WT ≤ Pro-G56W < Pro-G56S < Pro-G56E. The propeptides of these variants were also overproduced, purified, and characterized. The stability and inhibitory potency of these propeptides decreased in the order Tk-propeptide [propeptide of Tk-subtilisin (Gly1-Leu69)] ≥ G56W-propeptide > G56S-propeptide > G56E-propeptide, indicating that they are inversely correlated with the maturation rates of Pro7-Tk-subtilisin and its derivatives. The crystal structures of these propeptides determined in complex with S324A-subtilisin indicate that the conformation of the propeptide is altered by the mutation, such that nonglycine residues at position 56 assume a right-handed conformation and hydrophobic interactions at the core region decrease. These results indicate that Gly56 is required in stabilizing the propeptide fold. Stabilization of this fold leads to strong binding of Tk-propeptide to Tk-subtilisin, high resistance of Tk-propeptide to proteolytic degradation, and slow maturation of Pro-Tk-subtilisin.     

Inhibitory effects of different antioxidants on hyaluronan depolymerization

Hyaluronan (HA) was depolymerized by hydroxyl radicals generated from hydrogen peroxide and cupric ions. Inhibition of HA degradation by four well-known antioxidants was investigated, as HA can scavenge reactive oxygen species (ROS). Change in hyaluronan molecular weight was observed by size-exclusion chromatography. Inhibition of HA degradation was estimated from the retention times observed. It was found that HA degradation was inhibited in a clearly concentration-dependent manner by mannitol, thiourea and vinpocetine. Propofol also inhibited the depolymerization, but its concentration-dependent effect was not so clear. The antioxidant concentrations at which HA degradation was decreased by 50% were 42 microM for thiourea; 1.35 microM for vinpocetine; and 0.39 microM for propofol. A concentration of 26.51 mM of mannitol was needed to attain the same inhibitory effect. Although many factors are involved in a therapeutic response, the results obtained in this study support the idea that HA may be protected from ROS attack by the concomitant use of well-known antioxidants.