Prohibitin involvement in the generation of mitochondrial superoxide at complex I in human sperm

Prohibitin (PHB), a major mitochondrial membrane protein, has been shown earlier in our laboratoryto regulate sperm motility via an alteration in mitochondrial membrane potential (MMP) in infertile men with poor sperm quality. To test if PHB expression is associated with sperm mitochondrial superoxide (mROS) levels, here we examined sperm mROS levels, high MMP and lipid peroxidation in infertile men with poor sperm motility (asthenospermia, A) and/or low sperm concentrations (oligoasthenospermia, OA). The diaphorase‐type activity of sperm mitochondrial complex I (MCI) and PHB expression were also determined. We demonstrate that mROS and lipid peroxidation levels are significantly higher in sperm from A and OA subjects than in normospermic subjects, whereas high MMP and PHB expression are significantly lower. A positive correlation between mROS and lipid peroxidation and a negative correlation of mROS with PHB expression, high MMP, and sperm motility were found in these subjects. The finding of similar diaphorase‐type activity levels of sperm MCI in the three groups studied suggests that the catalytic subunits of MCI in the matrix arm may produce mROS on its own. There may be a dysfunction of electron transport at MCI associated with decreased expression of PHB in sperm with poor quality. We conclude that mROS level is increased and associated with decreased PHB expression, and it may regulate sperm motility via increases in low MMP and lipid peroxidation. This is the first report on the involvement of PHB in human sperm motility loss associated with increased generation of mROS at MCI.     

A B3LYP and MP2(full) theoretical investigation into cooperativity effects,aromaticity and thermodynamic properties in the Na+⋯benzonitrile⋯H2O ternary complex

In this work the growth of a graphene monolayer on copper substrate, as typically achieved via chemical vapor deposition of propene (C₃H₆), was investigated by first-principles and kinetic Monte Carlo calculations. A comparison between calculated C1s core-level binding energies and electron spectroscopy measurements showed that graphene nucleates from isolated carbon atoms adsorbed on surface defects or sub-superficial layers upon hydrocarbon fragmentation. In this respect, ab initio nudged elastic band simulations yield the energetic barriers characterizing the diffusion of elemental carbon on the Cu(111) surface and atomic carbon uptake by the growing graphene film. Our calculations highlight a strong interaction between the growing film edges and the copper substrate, indicative of the importance of the grain boundaries in the epitaxy process. Furthermore, we used activation energies to compute the reaction rates for the different mechanisms occurring at the carbon–copper interface via harmonic transition state theory. Finally, we simulated the long-time system growth evolution through a kinetic Monte Carlo approach for different temperatures and coverage. Our ab initio and Monte Carlo simulations of the out-of-equilibrium system point towards a growth model strikingly different from that of standard film growth. Graphene growth on copper turns out to be a catalytic, thermally-activated process that nucleates from carbon monomers, proceeds by adsorption of carbon atoms, and is not self-limiting. Furthermore, graphene growth seems to be more effective at carbon supersaturation of the surface—a clear fingerprint of a large activation barrier for C attachment. Our growth model and computational results are in good agreement with recent X-ray photoelectron spectroscopy experimental measurements.     

Non-imidazole heterocyclic histamine H3 receptor antagonists

Continued exploration of the SAR around the lead imidazopyridine histamine H(3) antagonist 1 has led to the discovery of several related series of heterocyclic histamine H(3) antagonists. The synthesis and SAR of indolizine, indole and pyrazolopyridine based compounds are now described.     

Production of xylanases from rice bran by Streptomyces actuosus A-151

In this study, the agricultural waste was used to screen for an organism that is capable of producing enzymes for degrading xylan and cellulose. Results showed that Streptomyces actuosus A-151, isolated from northern Taiwan, produced β-xylanase when rice bran was used as the sole carbon source. Four xylanases, designated as FI-A, FI-B, FII-A, FII-B, were identified and purified from the culture filtrate of S. actuosus A-151. Their specific activities after purification were 41.3, 86.2, 20.4, 85.2 U/mg, respectively. The pH stability of the four enzymes was: FI-A, 5–8; FI-B, 3–8; FII-A, 5–9; and FII-B, 3–9. The optimum pH for FII-B was 4, and the others were near 5–6. The optimum temperatures for enzyme activities were 60 °C for FII-B, and 70 °C for the others. The thermal stability for all four enzymes were up to 60 °C. The molecular weights of FI-A, FI-B, FII-A, and FII-B xylanases were 30,000, 45,000, 26,000, and 20,000, respectively, by sodium dodecylsulfate–polyacrylamide gel electrophoresis and 30,000, 43,000, 25,000, and 21,000, respectively, by gel filtration. Addition of xylan, shrimp and crab shell powder, and orange peel to the culture medium was found to enhance the production of xylanase.     

Reduction in omega-3 fatty acids by UV-B irradiation in microalgae

UV-B irradiation reduced the levels of omega-3 fatty acid, eicosapentaenoic acid (EPA, 20:53) and docosahexaenoic acid (DHA, 22:63), in microalgae; the degree of reduction varied with species.Chaetoceros calcitrans andSkeletonema costatum were high UV-B tolerant species, followed byPhaeodactylum tricornutum, Chroomonas salina, Pavlova lutheri, andThalassiosira pseudonana.Isochrysis galbana (T.ISO) andProrocentrum micans were UV- B sensitive. Cells in logarithmic phase were most sensitive to UV- B irradiation. Nitrate-, phosphate-, or sulphate-starved cells were more UV-B sensitive than non-starved cells grown in a complete basal medium. A relatively short exposure to high UV-B was more damaging than a longer exposure to lower irradiance. Visible light intensity levels had a profound impact on the sensitivity of microalgal cultures to UV-B, with high levels decreasing UV-B dependent damage. Addition of polyamines (putrescine, spermidine or spermine) or an amino acid (cysteine) to the culture medium minimized the reduction of omega-3 fatty acid content in microalgae caused by UV-B irradiation.Author for correspondence     

TGF-beta mediated Msx2 expression controls occipital somites-derived caudal region of skull development

Craniofacial development involves cranial neural crest (CNC) and mesoderm-derived cells. TGF-beta signaling plays a critical role in instructing CNC cells to form the craniofacial skeleton. However, it is not known how TGF-beta signaling regulates the fate of mesoderm-derived cells during craniofacial development. In this study, we show that occipital somites contribute to the caudal region of mammalian skull development. Conditional inactivation of Tgfbr2 in mesoderm-derived cells results in defects of the supraoccipital bone with meningoencephalocele and discontinuity of the neural arch of the C1 vertebra. At the cellular level, loss of TGF-beta signaling causes decreased chondrocyte proliferation and premature differentiation of cartilage to bone. Expression of Msx2, a critical factor in the formation of the dorsoventral axis, is diminished in the Tgfbr2 mutant. Significantly, overexpression of Msx2 in Myf5-Cre;Tgfbr2flox/flox mice partially rescues supraoccipital bone development. These results suggest that the TGF-beta/Msx2 signaling cascade is critical for development of the caudal region of the skull.     

Electric-field-induced spin switch of endohedral dodecahedrane heterodimers H@C<Subscript>20</Subscript>H<Subscript>n</Subscript>–C<Subscript>20</Subscript>H<Subscript>n</Subscript>@M (M= Cu,Ag and Au,n = 15, 18, and 19): a theoretical study

We designed nine endohedral dodecahedrane heterodimers H@C₂₀H_n-C₂₀H_n@M (M = Cu, Ag, and Au, n = 15, 18, and 19) that may act as single-molecule spin switches, and we predicted theoretically that the ground states of the dimmers shift from low-spin states (S = 0) to the high-spin states (S = 1) under an external electric field applied parallel or perpendicular to the molecular symmetry axes, consisting well with the analyses of Stark effect. Molecular orbitals analyses provide an intuitive insight into the spin crossover behavior. This study expands the application of endohedral chemistry and provides new molecules for designing single-molecule spin switch.     

Identification and characterization of a novel cold-tolerant extracellular protease from Planococcus sp. CGMCC 8088

Extremophiles - A psychrophilic extracellular protease was isolated from the marine bacterium Planococcus sp. M7 found in the deep-sea mud of the Southern Indian Ocean. The mature protease is about...     

The S4-S5 linker acts as a signal integrator for HERG K+ channel activation and deactivation gating

Human ether-à-go-go-related gene (hERG) K(+) channels have unusual gating kinetics. Characterised by slow activation/deactivation but rapid inactivation/recovery from inactivation, the unique gating kinetics underlie the central role hERG channels play in cardiac repolarisation. The slow activation and deactivation kinetics are regulated in part by the S4-S5 linker, which couples movement of the voltage sensor domain to opening of the activation gate at the distal end of the inner helix of the pore domain. It has also been suggested that cytosolic domains may interact with the S4-S5 linker to regulate activation and deactivation kinetics. Here, we show that the solution structure of a peptide corresponding to the S4-S5 linker of hERG contains an amphipathic helix. The effects of mutations at the majority of residues in the S4-S5 linker of hERG were consistent with the previously identified role in coupling voltage sensor movement to the activation gate. However, mutations to Ser543, Tyr545, Gly546 and Ala548 had more complex phenotypes indicating that these residues are involved in additional interactions. We propose a model in which the S4-S5 linker, in addition to coupling VSD movement to the activation gate, also contributes to interactions that stabilise the closed state and a separate set of interactions that stabilise the open state. The S4-S5 linker therefore acts as a signal integrator and plays a crucial role in the slow deactivation kinetics of the channel.     

ATL3 Is a Tubular ER-Phagy Receptor for GABARAP-Mediated Selective Autophagy

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