Sample records for lh2 reveals function

  1. Bioinspired Organic PV Cells Using Photosynthetic Pigment Complex for Energy Harvesting Materials

    DTIC Science & Technology

    2010-05-10

    ultrafast laser spectroscopy. More recently the structures of the LH2 complexes has revealed the nonameric or octameric arrangement of repeating units...Scheme 1. Compartimentalization of light harvesting and charge separation. The antenna complexes( LH2 ,LH1-RC) efficiently realize various...photosynthetic functions using cofactors (BChl a and carotenoid) assembled into the apoproteins (LH1 and LH2 ). The light-harvesting mechanisms in these

  2. Bio-Inspired Assembly of Artificial Photosynthetic Antenna Complexes for Development of Nanobiodevices

    DTIC Science & Technology

    2011-06-24

    extensively studied by ultrafast laser spectroscopy. More recently the structures of the LH2 complexes has revealed the nonameric and octameric arrangement of...Scheme 1). 4 Scheme 1. Compartimentalization of light harvesting and charge separation. The antenna complexes( LH2 ,LH1-RC) efficiently...realize various photosynthetic functions using cofactors (BChl a and carotenoid) assembled into the apoproteins (LH1 and LH2 ). The light-harvesting

  3. Assembly of Photosynthetic Antenna Protein Complexes from Algae for Development of Nano-biodevice and Its Fuelization

    DTIC Science & Technology

    2013-05-20

    More recently the structures of the LH2 complexes has revealed the nonameric and octameric arrangement of repeating units consisting of two...Compartimentalization of light -harvesting and charge separation. The antenna complexes( LH2 ,LH1-RC) efficiently realize various photosynthetic functions...using cofactors (BChl a and carotenoid) assembled into the apoproteins (LH1 and LH2 ). The light-harvesting mechanisms in these light-harvesting

  4. Assembly of Photosynthetic Antenna Protein / Pigments Complexes from Algae and Plants for Development of Nanobiodevices

    DTIC Science & Technology

    2012-07-10

    recently the structures of the LH2 complexes has revealed the nonameric and octameric arrangement of repeating units consisting of two apoproteins and...Compartimentalization of light -harvesting and charge separation. The antenna complexes( LH2 ,LH1-RC) efficiently realize various photosynthetic functions using...cofactors (BChl a and carotenoid) assembled into the apoproteins (LH1 and LH2 ). The light-harvesting mechanisms in these light-harvesting complexes have

  5. Molecular Level Design Principle behind Optimal Sizes of Photosynthetic LH2 Complex: Taming Disorder through Cooperation of Hydrogen Bonding and Quantum Delocalization.

    PubMed

    Jang, Seogjoo; Rivera, Eva; Montemayor, Daniel

    2015-03-19

    The light harvesting 2 (LH2) antenna complex from purple photosynthetic bacteria is an efficient natural excitation energy carrier with well-known symmetric structure, but the molecular level design principle governing its structure-function relationship is unknown. Our all-atomistic simulations of nonnatural analogues of LH2 as well as those of a natural LH2 suggest that nonnatural sizes of LH2-like complexes could be built. However, stable and consistent hydrogen bonding (HB) between bacteriochlorophyll and the protein is shown to be possible only near naturally occurring sizes, leading to significantly smaller disorder than for nonnatural ones. Extensive quantum calculations of intercomplex exciton transfer dynamics, sampled for a large set of disorder, reveal that taming the negative effect of disorder through a reliable HB as well as quantum delocalization of the exciton is a critical mechanism that makes LH2 highly functional, which also explains why the natural sizes of LH2 are indeed optimal.

  6. Function of membrane protein in silica nanopores: incorporation of photosynthetic light-harvesting protein LH2 into FSM.

    PubMed

    Oda, Ippei; Hirata, Kotaro; Watanabe, Syoko; Shibata, Yutaka; Kajino, Tsutomu; Fukushima, Yoshiaki; Iwai, Satoshi; Itoh, Shigeru

    2006-01-26

    A high amount of functional membrane protein complex was introduced into a folded-sheet silica mesoporous material (FSM) that has nanometer-size pores of honeycomb-like hexagonal cylindrical structure inside. The photosynthetic light-harvesting complex LH2, which is a typical membrane protein, has a cylindrical structure of 7.3 nm diameter and contains 27 bacteriochlorophyll a and nine carotenoid molecules. The complex captures light energy in the anoxygenic thermophilic purple photosynthetic bacterium Thermochromatium tepidum. The amount of LH2 adsorbed to FSM was determined optically and by the adsorption isotherms of N2. The FSM compounds with internal pore diameters of 7.9 and 2.7 nm adsorbed LH2 at 1.11 and 0.24 mg/mg FSM, respectively, suggesting the high specific affinity of LH2 to the interior of the hydrophobic nanopores with a diameter of 7.9 nm. The LH2 adsorbed to FSM showed almost intact absorption bands of bacteriochlorophylls, and was fully active in the capture and transfer of excitation energy. The LH2 complex inside the FSM showed increased heat stability of the exciton-type absorption band of bacteriochlorophylls (B850), suggesting higher circular symmetry. The environment inside the hydrophobic silica nanopores can be a new matrix for the membrane proteins to reveal their functions. The silica-membrane protein adduct will be useful for the construction of new probes and reaction systems.

  7. The electronically excited states of LH2 complexes from Rhodopseudomonas acidophila strain 10050 studied by time-resolved spectroscopy and dynamic Monte Carlo simulations. II. Homo-arrays of LH2 complexes reconstituted into phospholipid model membranes.

    PubMed

    Pflock, Tobias J; Oellerich, Silke; Krapf, Lisa; Southall, June; Cogdell, Richard J; Ullmann, G Matthias; Köhler, Jürgen

    2011-07-21

    We performed time-resolved spectroscopy on homoarrays of LH2 complexes from the photosynthetic purple bacterium Rhodopseudomonas acidophila. Variations of the fluorescence transients were monitored as a function of the excitation fluence and the repetition rate of the excitation. These parameters are directly related to the excitation density within the array and to the number of LH2 complexes that still carry a triplet state prior to the next excitation. Comparison of the experimental observations with results from dynamic Monte Carlo simulations for a model cluster of LH2 complexes yields qualitative agreement without the need for any free parameter and reveals the mutual relationship between energy transfer and annihilation processes.

  8. Extension of Light-Harvesting Ability of Photosynthetic Light-Harvesting Complex 2 (LH2) through Ultrafast Energy Transfer from Covalently Attached Artificial Chromophores.

    PubMed

    Yoneda, Yusuke; Noji, Tomoyasu; Katayama, Tetsuro; Mizutani, Naoto; Komori, Daisuke; Nango, Mamoru; Miyasaka, Hiroshi; Itoh, Shigeru; Nagasawa, Yutaka; Dewa, Takehisa

    2015-10-14

    Introducing appropriate artificial components into natural biological systems could enrich the original functionality. To expand the available wavelength range of photosynthetic bacterial light-harvesting complex 2 (LH2 from Rhodopseudomonas acidophila 10050), artificial fluorescent dye (Alexa Fluor 647: A647) was covalently attached to N- and C-terminal Lys residues in LH2 α-polypeptides with a molar ratio of A647/LH2 ≃ 9/1. Fluorescence and transient absorption spectroscopies revealed that intracomplex energy transfer from A647 to intrinsic chromophores of LH2 (B850) occurs in a multiexponential manner, with time constants varying from 440 fs to 23 ps through direct and B800-mediated indirect pathways. Kinetic analyses suggested that B800 chromophores mediate faster energy transfer, and the mechanism was interpretable in terms of Förster theory. This study demonstrates that a simple attachment of external chromophores with a flexible linkage can enhance the light harvesting activity of LH2 without affecting inherent functions of energy transfer, and can achieve energy transfer in the subpicosecond range. Addition of external chromophores, thus, represents a useful methodology for construction of advanced hybrid light-harvesting systems that afford solar energy in the broad spectrum.

  9. Single-molecule spectroscopy reveals photosynthetic LH2 complexes switch between emissive states

    PubMed Central

    Schlau-Cohen, Gabriela S.; Wang, Quan; Southall, June; Cogdell, Richard J.; Moerner, W. E.

    2013-01-01

    Photosynthetic organisms flourish under low light intensities by converting photoenergy to chemical energy with near unity quantum efficiency and under high light intensities by safely dissipating excess photoenergy and deleterious photoproducts. The molecular mechanisms balancing these two functions remain incompletely described. One critical barrier to characterizing the mechanisms responsible for these processes is that they occur within proteins whose excited-state properties vary drastically among individual proteins and even within a single protein over time. In ensemble measurements, these excited-state properties appear only as the average value. To overcome this averaging, we investigate the purple bacterial antenna protein light harvesting complex 2 (LH2) from Rhodopseudomonas acidophila at the single-protein level. We use a room-temperature, single-molecule technique, the anti-Brownian electrokinetic trap, to study LH2 in a solution-phase (nonperturbative) environment. By performing simultaneous measurements of fluorescence intensity, lifetime, and spectra of single LH2 complexes, we identify three distinct states and observe transitions occurring among them on a timescale of seconds. Our results reveal that LH2 complexes undergo photoactivated switching to a quenched state, likely by a conformational change, and thermally revert to the ground state. This is a previously unobserved, reversible quenching pathway, and is one mechanism through which photosynthetic organisms can adapt to changes in light intensities. PMID:23776245

  10. Single-molecule spectroscopy reveals photosynthetic LH2 complexes switch between emissive states.

    PubMed

    Schlau-Cohen, Gabriela S; Wang, Quan; Southall, June; Cogdell, Richard J; Moerner, W E

    2013-07-02

    Photosynthetic organisms flourish under low light intensities by converting photoenergy to chemical energy with near unity quantum efficiency and under high light intensities by safely dissipating excess photoenergy and deleterious photoproducts. The molecular mechanisms balancing these two functions remain incompletely described. One critical barrier to characterizing the mechanisms responsible for these processes is that they occur within proteins whose excited-state properties vary drastically among individual proteins and even within a single protein over time. In ensemble measurements, these excited-state properties appear only as the average value. To overcome this averaging, we investigate the purple bacterial antenna protein light harvesting complex 2 (LH2) from Rhodopseudomonas acidophila at the single-protein level. We use a room-temperature, single-molecule technique, the anti-Brownian electrokinetic trap, to study LH2 in a solution-phase (nonperturbative) environment. By performing simultaneous measurements of fluorescence intensity, lifetime, and spectra of single LH2 complexes, we identify three distinct states and observe transitions occurring among them on a timescale of seconds. Our results reveal that LH2 complexes undergo photoactivated switching to a quenched state, likely by a conformational change, and thermally revert to the ground state. This is a previously unobserved, reversible quenching pathway, and is one mechanism through which photosynthetic organisms can adapt to changes in light intensities.

  11. Effects of aggregation on the excitation dynamics of LH2 from Thermochromatium tepidum in aqueous phase and in chromatophores.

    PubMed

    Yang, Fan; Yu, Long-Jiang; Wang, Peng; Ai, Xi-Cheng; Wang, Zheng-Yu; Zhang, Jian-Ping

    2011-06-23

    We carried out femtosecond magic-angle and polarized pump-probe spectroscopies for the light-harvesting complex 2 (LH2) from Thermochromatium (Tch.) tepidum in aqueous phase and in chromatophores. To examine the effects of LH2 aggregation on the dynamics of excitation energy transfer, dominant monodispersed and aggregated LH2s were prepared by controlling the surfactant concentrations. The aqueous preparations solubilized with different concentrations of n-dodecyl-β-D-maltoside (DDM) show similar visible-to-near-infrared absorption spectra, but distinctively different aggregation states, as revealed by using dynamic light scattering. The B800 → B850 intra-LH2 energy transfer time was determined to be 1.3 ps for isolated LH2, which, upon aggregation in aqueous phase or clustering in chromatophores, shortened to 1.1 or 0.9 ps, respectively. The light-harvesting complex 1 (LH1) of this thermophilic purple sulfur bacterium contains bacteriochlorophyll a absorbing at 915 nm (B915), and the LH2(B850) → LH1(B915) intercomplex transfer time in chromatophores was found to be 6.6 ps. For chromatophores, a depolarization time of 21 ps was derived from the anisotropy kinetics of B850*, which is attributed to the migration of B850* excitation before being trapped by LH1. In addition, the B850* annihilation is accelerated upon LH2 aggregation in aqueous phase, but it is much less severe upon LH2 clustering in the intracytoplasmic membrane. These results are helpful in understanding the light-harvesting function of a bacterial photosynthetic membrane incorporating different types of antenna complexes.

  12. Energy transfer in light-adapted photosynthetic membranes: from active to saturated photosynthesis.

    PubMed

    Fassioli, Francesca; Olaya-Castro, Alexandra; Scheuring, Simon; Sturgis, James N; Johnson, Neil F

    2009-11-04

    In bacterial photosynthesis light-harvesting complexes, LH2 and LH1 absorb sunlight energy and deliver it to reaction centers (RCs) with extraordinarily high efficiency. Submolecular resolution images have revealed that both the LH2:LH1 ratio, and the architecture of the photosynthetic membrane itself, adapt to light intensity. We investigate the functional implications of structural adaptations in the energy transfer performance in natural in vivo low- and high-light-adapted membrane architectures of Rhodospirillum photometricum. A model is presented to describe excitation migration across the full range of light intensities that cover states from active photosynthesis, where all RCs are available for charge separation, to saturated photosynthesis where all RCs are unavailable. Our study outlines three key findings. First, there is a critical light-energy density, below which the low-light adapted membrane is more efficient at absorbing photons and generating a charge separation at RCs, than the high-light-adapted membrane. Second, connectivity of core complexes is similar in both membranes, suggesting that, despite different growth conditions, a preferred transfer pathway is through core-core contacts. Third, there may be minimal subareas on the membrane which, containing the same LH2:LH1 ratio, behave as minimal functional units as far as excitation transfer efficiency is concerned.

  13. Involvement of the C-terminal extension of the alpha polypeptide and of the PucC protein in LH2 complex biosynthesis in Rubrivivax gelatinosus.

    PubMed

    Steunou, Anne-Soisig; Ouchane, Soufian; Reiss-Husson, Françoise; Astier, Chantal

    2004-05-01

    The facultative phototrophic nonsulfur bacterium Rubrivivax gelatinosus exhibits several differences from other species of purple bacteria in the organization of its photosynthetic genes. In particular, the puc operon contains only the pucB and pucA genes encoding the beta and alpha polypeptides of the light-harvesting 2 (LH2) complex. Downstream of the pucBA operon is the pucC gene in the opposite transcriptional orientation. The transcription of pucBA and pucC has been studied. No pucC transcript was detected either by Northern blotting or by reverse transcription-PCR analysis. The initiation site of pucBA transcription was determined by primer extension, and Northern blot analysis revealed the presence of two transcripts of 0.8 and 0.65 kb. The half-lives of both transcripts are longer in cells grown semiaerobically than in photosynthetically grown cells, and the small transcript is the less stable. It was reported that the alpha polypeptide, encoded by the pucA gene, presents a C-terminal extension which is not essential for LH2 function in vitro. The biological role of this alanine- and proline-rich C-terminal extension in vivo has been investigated. Two mutants with C-terminal deletions of 13 and 18 residues have been constructed. Both present the two pucBA transcripts, while their phenotypes are, respectively, LH2+ and LH2-, suggesting that a minimal length of the C-terminal extension is required for LH2 biogenesis. Another important factor involved in the LH2 biogenesis is the PucC protein. To gain insight into the function of this protein in R. gelatinosus, we constructed and characterized a PucC mutant. The mutant is devoid of LH2 complex under semiaerobiosis but still produces a small amount of these antennae under photosynthetic growth conditions. This conditional phenotype suggests the involvement of another factor in LH2 biogenesis.

  14. Clades of Photosynthetic Bacteria Belonging to the Genus Rhodopseudomonas Show Marked Diversity in Light-Harvesting Antenna Complex Gene Composition and Expression

    DOE PAGES

    Fixen, Kathryn R.; Oda, Yasuhiro; Harwood, Caroline S.; ...

    2015-12-22

    Many photosynthetic bacteria have peripheral light-harvesting (LH) antenna complexes that increase the efficiency of light energy capture. The purple nonsulfur photosynthetic bacteriumRhodopseudomonas palustrisproduces different types of LH complexes under high light intensities (LH2 complex) and low light intensities (LH3 and LH4 complexes). There are multiplepucBAoperons that encode the α and β peptides that make up these complexes. But, low-resolution structures, amino acid similarities between the complexes, and a lack of transcription analysis have made it difficult to determine the contributions of differentpucBAoperons to the composition and function of different LH complexes. It was also unclear how much diversity of LHmore » complexes exists inR. palustrisand affiliated strains. To address this, we undertook an integrative genomics approach using 20 sequenced strains. Gene content analysis revealed that even closely related strains have differences in theirpucBAgene content. Transcriptome analyses of the strains grown under high light and low light revealed that the patterns of expression of thepucBAoperons varied among strains grown under the same conditions. We also found that one set of LH2 complex proteins compensated for the lack of an LH4 complex under low light intensities but not under extremely low light intensities, indicating that there is functional redundancy between some of the LH complexes under certain light intensities. The variation observed in LH gene composition and expression inRhodopseudomonasstrains likely reflects how they have evolved to adapt to light conditions in specific soil and water microenvironments. ImportanceRhodopseudomonas palustrisis a phototrophic purple nonsulfur bacterium that adapts its photosystem to allow growth at a range of light intensities. It does this by adjusting the amount and composition of peripheral light-harvesting (LH) antenna complexes that it synthesizes.Rhodopseudomonasstrains are notable for containing numerous sets of light-harvesting genes. We determined the diversity of LH complexes and their transcript levels during growth under high and low light intensities in 20 sequenced genomes of strains related to the speciesRhodopseudomonas palustris. Finally, the data obtained are a resource for investigators with interests as wide-ranging as the biophysics of photosynthesis, the ecology of phototrophic bacteria, and the use of photosynthetic bacteria for biotechnology applications.« less

  15. Clades of Photosynthetic Bacteria Belonging to the Genus Rhodopseudomonas Show Marked Diversity in Light-Harvesting Antenna Complex Gene Composition and Expression

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fixen, Kathryn R.; Oda, Yasuhiro; Harwood, Caroline S.

    Many photosynthetic bacteria have peripheral light-harvesting (LH) antenna complexes that increase the efficiency of light energy capture. The purple nonsulfur photosynthetic bacteriumRhodopseudomonas palustrisproduces different types of LH complexes under high light intensities (LH2 complex) and low light intensities (LH3 and LH4 complexes). There are multiplepucBAoperons that encode the α and β peptides that make up these complexes. But, low-resolution structures, amino acid similarities between the complexes, and a lack of transcription analysis have made it difficult to determine the contributions of differentpucBAoperons to the composition and function of different LH complexes. It was also unclear how much diversity of LHmore » complexes exists inR. palustrisand affiliated strains. To address this, we undertook an integrative genomics approach using 20 sequenced strains. Gene content analysis revealed that even closely related strains have differences in theirpucBAgene content. Transcriptome analyses of the strains grown under high light and low light revealed that the patterns of expression of thepucBAoperons varied among strains grown under the same conditions. We also found that one set of LH2 complex proteins compensated for the lack of an LH4 complex under low light intensities but not under extremely low light intensities, indicating that there is functional redundancy between some of the LH complexes under certain light intensities. The variation observed in LH gene composition and expression inRhodopseudomonasstrains likely reflects how they have evolved to adapt to light conditions in specific soil and water microenvironments. ImportanceRhodopseudomonas palustrisis a phototrophic purple nonsulfur bacterium that adapts its photosystem to allow growth at a range of light intensities. It does this by adjusting the amount and composition of peripheral light-harvesting (LH) antenna complexes that it synthesizes.Rhodopseudomonasstrains are notable for containing numerous sets of light-harvesting genes. We determined the diversity of LH complexes and their transcript levels during growth under high and low light intensities in 20 sequenced genomes of strains related to the speciesRhodopseudomonas palustris. Finally, the data obtained are a resource for investigators with interests as wide-ranging as the biophysics of photosynthesis, the ecology of phototrophic bacteria, and the use of photosynthetic bacteria for biotechnology applications.« less

  16. [Influence of LDAO on the conformation and release of bacteriochlorophyll of peripheral light-harvesting complex (LH2) from Rhodobacter azotoformans].

    PubMed

    Zhao, Gen-gui; Dong, Yan-min; Yang, Su-ping; Jiao, Nian-zhi; Qu, Yin-bo

    2010-10-01

    The aim of this study is to reveal the interaction relationships between lauryl dimethylamine N-oxide (LDAO) and peripheral light-harvesting complex (LH2) as well as the influence of LDAO on structure and function of LH2. In the present work, the effects of LDAO on the conformation and release processes of bacteriochlorophyll (BChl) of LH2 when incubated under different temperature and pH in the presence and absence of LDAO were investigated by spectroscopy. The results indicated that (1) the presence of LDAO resulted in alterations in the conformation, alpha-helix content, and spectra of Tyr and B850 band of LH2 at room temperature and pH 8.0. Moreover, energy transfer efficiency of LH2 was enhanced markedly in the presence of LDAO. (2) At 60 degrees C, both the B800 and B850 band of LH2 were released and transited into free BChl at pH 8.0. However, the release rates of bacteriochlorophylls of B800 and B850 band from LH2 were slowed down and the release processes were changed when incubated in the presence of LDAO. Hence, the stability of LH2 was improved in the presence of LDAO. (3) The accelerated release processes of bacteriochlorophylls of B800 and B850 band of LH2 were induced to transform into bacteriopheophytin (BPhe) and free BChl by LDAO in strong acid and strong alkalic solution at room temperature. However, the kinetic patterns of the B800 and B850 band were remarkably different. The release and self-assemble processes of B850 in LH2 were observed in strong acid solution without LDAO. Therefore, the different release behaviors of B800 and B850 of LH2 are induced by LDAO under different extreme environmental conditions.

  17. Fetal programming: testosterone exposure of the female sheep during midgestation disrupts the dynamics of its adult gonadotropin secretion during the periovulatory period.

    PubMed

    Savabieasfahani, Mozhgan; Lee, James S; Herkimer, Carol; Sharma, Tejinder P; Foster, Douglas L; Padmanabhan, Vasantha

    2005-01-01

    Prenatal exposure of the female sheep to excess testosterone (T) leads to hypergonadotropism, multifollicular ovaries, and progressive loss of reproductive cycles. We have determined that prenatal T treatment delays the latency of the estradiol (E2)-induced LH surge. To extend this finding into a natural physiological context, the present study was conducted to determine if the malprogrammed surge mechanism alters the reproductive cycle. Specifically, we wished to determine if prenatal T treatment 1) delays the onset of the preovulatory gonadotropin surge during the natural follicular phase rise in E2, 2) alters pulsatile LH secretion and the dynamics of the secondary FSH surge, and 3) compromises the ensuing luteal function. Females prenatally T-treated from Day 60 to Day 90 of gestation (147 days is term) and control females were studied when they were approximately 2.5 yr of age. Reproductive cycles of control and prenatally T-treated females were synchronized with PGF2alpha, and peripheral blood samples were collected every 2 h for 120 h to characterize cyclic changes in E2, LH, and FSH and then daily for 14 days to monitor changes in luteal progesterone. To assess LH pulse patterns, blood samples were also collected frequently (each 5 min for 6 h) during the follicular and luteal phases of the cycle. The results revealed that, in prenatally T-treated females, 1) the preovulatory increase in E2 was normal; 2) the latencies between the preovulatory increase in E2 and the peaks of the primary LH and FSH surges were longer, but the magnitudes similar; 3) follicular-phase LH pulse frequency was increased; 4) the interval between the primary and secondary FSH surges was reduced but there was a tendency for an increase in duration of the secondary FSH surge; but 5) luteal progesterone patterns were in general unaltered. Thus, exposure of the female to excess T before birth produces perturbances and maltiming in periovulatory gonadotropin secretory dynamics, but these do not produce apparent defects in cycle regularity or luteal function. To reveal the pathologies that lead to the eventual subfertility arising from excess T exposure during midgestation, studies at older ages must be conducted to assess if there is progressive disruption of neuroendocrine and ovarian function.

  18. Synthesis, crystal structure and valence tautomerism of a 4,4‧-bipyridine-bridged one-dimensional chiral cobalt complex

    NASA Astrophysics Data System (ADS)

    Cheng, Wei-Qin; Li, Guo-Ling; Zhang, Ran; Ni, Zhong-Hai; Wang, Wen-Feng; Sato, Osamu

    2015-05-01

    A linear-chain cobalt coordination polymer, [Co(2,3-LH2)2(4,4‧-bipy)]ṡ2H2Oṡ4,4‧-bipy]n (1) (2,3-LH2 = 2,3-tetrahydroxy-9,10-dimethyl-9,10-dihydro- 9,10-ethanoanthracene, 4,4‧-bipy = 4,4‧-bipyridine), has been synthesized and structurally characterized. Single-crystal X-ray analysis reveals that complex 1 is a chiral polymer assemblied from achiral components. The complex 1 crystallizes in the chiral space group P3221 and the central Co ion has a slightly distorted octahedral coordination environment. The temperature dependence of magnetic susceptibility indicates that the complex 1 undergoes valence tautomeric interconversion between low-spin ls-[CoIII(2,3-LH2Cat)(2,3-LH2SQ)] and high-spin hs-[CoII(2,3-LH2SQ)2] (2,3-LH2Cat = 2,3-LH2catecholate, 2,3-LH2SQ = 2,3-LH2semiquinone).

  19. High-resolution AFM topographs of Rubrivivax gelatinosus light-harvesting complex LH2

    PubMed Central

    Scheuring, Simon; Reiss-Husson, Francoise; Engel, Andreas; Rigaud, Jean-Louis; Ranck, Jean-Luc

    2001-01-01

    Light-harvesting complexes 2 (LH2) are the accessory antenna proteins in the bacterial photosynthetic apparatus and are built up of αβ-heterodimers containing three bacteriochlorophylls and one carotenoid each. We have used atomic force microscopy (AFM) to investigate reconstituted LH2 from Rubrivivax gelatinosus, which has a C-terminal hydrophobic extension of 21 amino acids on the α-subunit. High-resolution topographs revealed a nonameric organization of the regularly packed cylindrical complexes incorporated into the membrane in both orientations. Native LH2 showed one surface which protruded by ∼6 Å and one that protruded by ∼14 Å from the membrane. Topographs of samples reconstituted with thermolysin-digested LH2 revealed a height reduction of the strongly protruding surface to ∼9 Å, and a change of its surface appearance. These results suggested that the α-subunit of R.gelatinosus comprises a single transmembrane helix and an extrinsic C-terminus, and allowed the periplasmic surface to be assigned. Occasionally, large rings (∼120 Å diameter) surrounded by LH2 rings were observed. Their diameter and appearance suggest the large rings to be LH1 complexes. PMID:11406579

  20. Role of an elliptical structure in photosynthetic energy transfer: Collaboration between quantum entanglement and thermal fluctuation

    PubMed Central

    Oka, Hisaki

    2016-01-01

    Recent experiments have revealed that the light-harvesting complex 1 (LH1) in purple photosynthetic bacteria has an elliptical structure. Generally, symmetry lowering in a structure leads to a decrease in quantum effects (quantum coherence and entanglement), which have recently been considered to play a role in photosynthetic energy transfer, and hence, elliptical structure seems to work against efficient photosynthetic energy transfer. Here we analyse the effect of an elliptical structure on energy transfer in a purple photosynthetic bacterium and reveal that the elliptical distortion rather enhances energy transfer from peripheral LH2 to LH1 at room temperature. Numerical results show that quantum entanglement between LH1 and LH2 is formed over a wider range of high energy levels than would have been the case with circular LH1. Light energy absorbed by LH2 is thermally pumped via thermal fluctuation and is effectively transferred to LH1 through the entangled states at room temperature rather than at low temperature. This result indicates the possibility that photosynthetic systems adopt an elliptical structure to effectively utilise both quantum entanglement and thermal fluctuation at physiological temperature. PMID:27173144

  1. Role of an elliptical structure in photosynthetic energy transfer: Collaboration between quantum entanglement and thermal fluctuation

    NASA Astrophysics Data System (ADS)

    Oka, Hisaki

    2016-05-01

    Recent experiments have revealed that the light-harvesting complex 1 (LH1) in purple photosynthetic bacteria has an elliptical structure. Generally, symmetry lowering in a structure leads to a decrease in quantum effects (quantum coherence and entanglement), which have recently been considered to play a role in photosynthetic energy transfer, and hence, elliptical structure seems to work against efficient photosynthetic energy transfer. Here we analyse the effect of an elliptical structure on energy transfer in a purple photosynthetic bacterium and reveal that the elliptical distortion rather enhances energy transfer from peripheral LH2 to LH1 at room temperature. Numerical results show that quantum entanglement between LH1 and LH2 is formed over a wider range of high energy levels than would have been the case with circular LH1. Light energy absorbed by LH2 is thermally pumped via thermal fluctuation and is effectively transferred to LH1 through the entangled states at room temperature rather than at low temperature. This result indicates the possibility that photosynthetic systems adopt an elliptical structure to effectively utilise both quantum entanglement and thermal fluctuation at physiological temperature.

  2. Role of an elliptical structure in photosynthetic energy transfer: Collaboration between quantum entanglement and thermal fluctuation.

    PubMed

    Oka, Hisaki

    2016-05-13

    Recent experiments have revealed that the light-harvesting complex 1 (LH1) in purple photosynthetic bacteria has an elliptical structure. Generally, symmetry lowering in a structure leads to a decrease in quantum effects (quantum coherence and entanglement), which have recently been considered to play a role in photosynthetic energy transfer, and hence, elliptical structure seems to work against efficient photosynthetic energy transfer. Here we analyse the effect of an elliptical structure on energy transfer in a purple photosynthetic bacterium and reveal that the elliptical distortion rather enhances energy transfer from peripheral LH2 to LH1 at room temperature. Numerical results show that quantum entanglement between LH1 and LH2 is formed over a wider range of high energy levels than would have been the case with circular LH1. Light energy absorbed by LH2 is thermally pumped via thermal fluctuation and is effectively transferred to LH1 through the entangled states at room temperature rather than at low temperature. This result indicates the possibility that photosynthetic systems adopt an elliptical structure to effectively utilise both quantum entanglement and thermal fluctuation at physiological temperature.

  3. Construction and Structural Analysis of Tethered Lipid Bilayer Containing Photosynthetic Antenna Proteins for Functional Analysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sumino, Ayumi; Dewa, Takehisa; Takeuchi, Toshikazu

    2011-07-11

    The construction and structural analysis of a tethered planar lipid bilayer containing bacterial photosynthetic membrane proteins, light-harvesting complex 2 (LH2), and light-harvesting core complex (LH1-RC) is described and establishes this system as an experimental platform for their functional analysis. The planar lipid bilayer containing LH2 and/or LH1-RC complexes was successfully formed on an avidin-immobilized coverglass via an avidin-biotin linkage. Atomic force microscopy (AFM) showed that a smooth continuous membrane was formed there. Lateral diffusion of these membrane proteins, observed by a fluorescence recovery after photobleaching (FRAY), is discussed in terms of the membrane architecture. Energy transfer from LH2 to LH1-RCmore » within the tethered membrane architecture. Energy transfer from LH2 to LH1-RC within the tethered membrane was observed by steady-state fluorescence spectroscopy, indicating that the tethered membrane can mimic the natural situation.« less

  4. The organization of LH2 complexes in membranes from Rhodobacter sphaeroides.

    PubMed

    Olsen, John D; Tucker, Jaimey D; Timney, John A; Qian, Pu; Vassilev, Cvetelin; Hunter, C Neil

    2008-11-07

    The mapping of the photosynthetic membrane of Rhodobacter sphaeroides by atomic force microscopy (AFM) revealed a unique organization of arrays of dimeric reaction center-light harvesting I-PufX (RC-LH1-PufX) core complexes surrounded and interconnected by light-harvesting LH2 complexes (Bahatyrova, S., Frese, R. N., Siebert, C. A., Olsen, J. D., van der Werf, K. O., van Grondelle, R., Niederman, R. A., Bullough, P. A., Otto, C., and Hunter, C. N. (2004) Nature 430, 1058-1062). However, membrane regions consisting solely of LH2 complexes were under-represented in these images because these small, highly curved areas of membrane rendered them difficult to image even using gentle tapping mode AFM and impossible with contact mode AFM. We report AFM imaging of membranes prepared from a mutant of R. sphaeroides, DPF2G, that synthesizes only the LH2 complexes, which assembles spherical intracytoplasmic membrane vesicles of approximately 53 nm diameter in vivo. By opening these vesicles and adsorbing them onto mica to form small, < or =120 nm, largely flat sheets we have been able to visualize the organization of these LH2-only membranes for the first time. The transition from highly curved vesicle to the planar sheet is accompanied by a change in the packing of the LH2 complexes such that approximately half of the complexes are raised off the mica surface by approximately 1 nm relative to the rest. This vertical displacement produces a very regular corrugated appearance of the planar membrane sheets. Analysis of the topographs was used to measure the distances and angles between the complexes. These data are used to model the organization of LH2 complexes in the original, curved membrane. The implications of this architecture for the light harvesting function and diffusion of quinones in native membranes of R. sphaeroides are discussed.

  5. Communication: Broad manifold of excitonic states in light-harvesting complex 1 promotes efficient unidirectional energy transfer in vivo

    NASA Astrophysics Data System (ADS)

    Sohail, Sara H.; Dahlberg, Peter D.; Allodi, Marco A.; Massey, Sara C.; Ting, Po-Chieh; Martin, Elizabeth C.; Hunter, C. Neil; Engel, Gregory S.

    2017-10-01

    In photosynthetic organisms, the pigment-protein complexes that comprise the light-harvesting antenna exhibit complex electronic structures and ultrafast dynamics due to the coupling among the chromophores. Here, we present absorptive two-dimensional (2D) electronic spectra from living cultures of the purple bacterium, Rhodobacter sphaeroides, acquired using gradient assisted photon echo spectroscopy. Diagonal slices through the 2D lineshape of the LH1 stimulated emission/ground state bleach feature reveal a resolvable higher energy population within the B875 manifold. The waiting time evolution of diagonal, horizontal, and vertical slices through the 2D lineshape shows a sub-100 fs intra-complex relaxation as this higher energy population red shifts. The absorption (855 nm) of this higher lying sub-population of B875 before it has red shifted optimizes spectral overlap between the LH1 B875 band and the B850 band of LH2. Access to an energetically broad distribution of excitonic states within B875 offers a mechanism for efficient energy transfer from LH2 to LH1 during photosynthesis while limiting back transfer. Two-dimensional lineshapes reveal a rapid decay in the ground-state bleach/stimulated emission of B875. This signal, identified as a decrease in the dipole strength of a strong transition in LH1 on the red side of the B875 band, is assigned to the rapid localization of an initially delocalized exciton state, a dephasing process that frustrates back transfer from LH1 to LH2.

  6. Atomic force microscopy studies of native photosynthetic membranes.

    PubMed

    Sturgis, James N; Tucker, Jaimey D; Olsen, John D; Hunter, C Neil; Niederman, Robert A

    2009-05-05

    In addition to providing the earliest surface images of a native photosynthetic membrane at submolecular resolution, examination of the intracytoplasmic membrane (ICM) of purple bacteria by atomic force microscopy (AFM) has revealed a wide diversity of species-dependent arrangements of closely packed light-harvesting (LH) antennae, capable of fulfilling the basic requirements for efficient collection, transmission, and trapping of radiant energy. A highly organized architecture was observed with fused preparations of the pseudocrystalline ICM of Blastochloris viridis, consiting of hexagonally packed monomeric reaction center light-harvesting 1 (RC-LH1) core complexes. Among strains which also form a peripheral LH2 antenna, images of ICM patches from Rhodobacter sphaeroides exhibited well-ordered, interconnected networks of dimeric RC-LH1 core complexes intercalated by rows of LH2, coexisting with LH2-only domains. Other peripheral antenna-containing species, notably Rhodospirillum photometricum and Rhodopseudomonas palustris, showed a less regular organization, with mixed regions of LH2 and RC-LH1 cores, intermingled with large, paracrystalline domains. The ATP synthase and cytochrome bc(1) complex were not observed in any of these topographs and are thought to be localized in the adjacent cytoplasmic membrane or in inaccessible ICM regions separated from the flat regions imaged by AFM. The AFM images have served as a basis for atomic-resolution modeling of the ICM vesicle surface, as well as forces driving segregation of photosynthetic complexes into distinct domains. Docking of atomic-resolution molecular structures into AFM topographs of Rsp. photometricum membranes generated precise in situ structural models of the core complex surrounded by LH2 rings and a region of tightly packed LH2 complexes. A similar approach has generated a model of the highly curved LH2-only membranes of Rba. sphaeroides which predicts that sufficient space exists between LH2 complexes for quinones to diffuse freely. Measurement of the intercomplex distances between adjacent LH2 rings of Phaeospirillum molischianum has permitted the first calculation of the separation of bacteriochlorophyll a molecules in the native ICM. A recent AFM analysis of the organization of green plant photosystem II (PSII) in grana thylakoids revealed the protruding oxygen-evolving complex, crowded together in parallel alignment at three distinct levels of stacked membranes over the lumenal surface. The results also confirmed that PSII-LHCII supercomplexes are displaced relative to one another in opposing grana membranes.

  7. The shift of microbial communities and their roles in sulfur and iron cycling in a copper ore bioleaching system.

    PubMed

    Niu, Jiaojiao; Deng, Jie; Xiao, Yunhua; He, Zhili; Zhang, Xian; Van Nostrand, J D; Liang, Yili; Deng, Ye; Liu, Xueduan; Yin, Huaqun

    2016-10-04

    Bioleaching has been employed commercially to recover metals from low grade ores, but the production efficiency remains to be improved due to limited understanding of the system. This study examined the shift of microbial communities and S&Fe cycling in three subsystems within a copper ore bioleaching system: leaching heap (LH), leaching solution (LS) and sediment under LS. Results showed that both LH and LS had higher relative abundance of S and Fe oxidizing bacteria, while S and Fe reducing bacteria were more abundant in the Sediment. GeoChip analysis showed a stronger functional potential for S 0 oxidation in LH microbial communities. These findings were consistent with measured oxidation activities to S 0 and Fe 2+ , which were highest by microbial communities from LH, lower by those from LS and lowest form Sediment. Moreover, phylogenetic molecular ecological network analysis indicated that these differences might be related to interactions among microbial taxa. Last but not the least, a conceptual model was proposed, linking the S&Fe cycling with responsible microbial populations in the bioleaching systems. Collectively, this study revealed the microbial community and functional structures in all three subsystems of the copper ore, and advanced a holistic understanding of the whole bioleaching system.

  8. The shift of microbial communities and their roles in sulfur and iron cycling in a copper ore bioleaching system

    NASA Astrophysics Data System (ADS)

    Niu, Jiaojiao; Deng, Jie; Xiao, Yunhua; He, Zhili; Zhang, Xian; van Nostrand, J. D.; Liang, Yili; Deng, Ye; Liu, Xueduan; Yin, Huaqun

    2016-10-01

    Bioleaching has been employed commercially to recover metals from low grade ores, but the production efficiency remains to be improved due to limited understanding of the system. This study examined the shift of microbial communities and S&Fe cycling in three subsystems within a copper ore bioleaching system: leaching heap (LH), leaching solution (LS) and sediment under LS. Results showed that both LH and LS had higher relative abundance of S and Fe oxidizing bacteria, while S and Fe reducing bacteria were more abundant in the Sediment. GeoChip analysis showed a stronger functional potential for S0 oxidation in LH microbial communities. These findings were consistent with measured oxidation activities to S0 and Fe2+, which were highest by microbial communities from LH, lower by those from LS and lowest form Sediment. Moreover, phylogenetic molecular ecological network analysis indicated that these differences might be related to interactions among microbial taxa. Last but not the least, a conceptual model was proposed, linking the S&Fe cycling with responsible microbial populations in the bioleaching systems. Collectively, this study revealed the microbial community and functional structures in all three subsystems of the copper ore, and advanced a holistic understanding of the whole bioleaching system.

  9. The shift of microbial communities and their roles in sulfur and iron cycling in a copper ore bioleaching system

    PubMed Central

    Niu, Jiaojiao; Deng, Jie; Xiao, Yunhua; He, Zhili; Zhang, Xian; Van Nostrand, J. D.; Liang, Yili; Deng, Ye; Liu, Xueduan; Yin, Huaqun

    2016-01-01

    Bioleaching has been employed commercially to recover metals from low grade ores, but the production efficiency remains to be improved due to limited understanding of the system. This study examined the shift of microbial communities and S&Fe cycling in three subsystems within a copper ore bioleaching system: leaching heap (LH), leaching solution (LS) and sediment under LS. Results showed that both LH and LS had higher relative abundance of S and Fe oxidizing bacteria, while S and Fe reducing bacteria were more abundant in the Sediment. GeoChip analysis showed a stronger functional potential for S0 oxidation in LH microbial communities. These findings were consistent with measured oxidation activities to S0 and Fe2+, which were highest by microbial communities from LH, lower by those from LS and lowest form Sediment. Moreover, phylogenetic molecular ecological network analysis indicated that these differences might be related to interactions among microbial taxa. Last but not the least, a conceptual model was proposed, linking the S&Fe cycling with responsible microbial populations in the bioleaching systems. Collectively, this study revealed the microbial community and functional structures in all three subsystems of the copper ore, and advanced a holistic understanding of the whole bioleaching system. PMID:27698381

  10. Genome-Wide Immune Modulation of TLR3-Mediated Inflammation in Intestinal Epithelial Cells Differs between Single and Multi-Strain Probiotic Combination.

    PubMed

    MacPherson, Chad W; Shastri, Padmaja; Mathieu, Olivier; Tompkins, Thomas A; Burguière, Pierre

    2017-01-01

    Genome-wide transcriptional analysis in intestinal epithelial cells (IEC) can aid in elucidating the impact of single versus multi-strain probiotic combinations on immunological and cellular mechanisms of action. In this study we used human expression microarray chips in an in vitro intestinal epithelial cell model to investigate the impact of three probiotic bacteria, Lactobacillus helveticus R0052 (Lh-R0052), Bifidobacterium longum subsp. infantis R0033 (Bl-R0033) and Bifidobacterium bifidum R0071 (Bb-R0071) individually and in combination, and of a surface-layer protein (SLP) purified from Lh-R0052, on HT-29 cells' transcriptional profile to poly(I:C)-induced inflammation. Hierarchical heat map clustering, Set Distiller and String analyses revealed that the effects of Lh-R0052 and Bb-R0071 diverged from those of Bl-R0033 and Lh-R0052-SLP. It was evident from the global analyses with respect to the immune, cellular and homeostasis related pathways that the co-challenge with probiotic combination (PC) vastly differed in its effect from the single strains and Lh-R0052-SLP treatments. The multi-strain PC resulted in a greater reduction of modulated genes, found through functional connections between immune and cellular pathways. Cytokine and chemokine analyses based on specific outcomes from the TNF-α and NF-κB signaling pathways revealed single, multi-strain and Lh-R0052-SLP specific attenuation of the majority of proteins measured (TNF-α, IL-8, CXCL1, CXCL2 and CXCL10), indicating potentially different mechanisms. These findings indicate a synergistic effect of the bacterial combinations relative to the single strain and Lh-R0052-SLP treatments in resolving toll-like receptor 3 (TLR3)-induced inflammation in IEC and maintaining cellular homeostasis, reinforcing the rationale for using multi-strain formulations as a probiotic.

  11. Genome-Wide Immune Modulation of TLR3-Mediated Inflammation in Intestinal Epithelial Cells Differs between Single and Multi-Strain Probiotic Combination

    PubMed Central

    MacPherson, Chad W.; Shastri, Padmaja; Mathieu, Olivier; Tompkins, Thomas A.; Burguière, Pierre

    2017-01-01

    Genome-wide transcriptional analysis in intestinal epithelial cells (IEC) can aid in elucidating the impact of single versus multi-strain probiotic combinations on immunological and cellular mechanisms of action. In this study we used human expression microarray chips in an in vitro intestinal epithelial cell model to investigate the impact of three probiotic bacteria, Lactobacillus helveticus R0052 (Lh-R0052), Bifidobacterium longum subsp. infantis R0033 (Bl-R0033) and Bifidobacterium bifidum R0071 (Bb-R0071) individually and in combination, and of a surface-layer protein (SLP) purified from Lh-R0052, on HT-29 cells’ transcriptional profile to poly(I:C)-induced inflammation. Hierarchical heat map clustering, Set Distiller and String analyses revealed that the effects of Lh-R0052 and Bb-R0071 diverged from those of Bl-R0033 and Lh-R0052-SLP. It was evident from the global analyses with respect to the immune, cellular and homeostasis related pathways that the co-challenge with probiotic combination (PC) vastly differed in its effect from the single strains and Lh-R0052-SLP treatments. The multi-strain PC resulted in a greater reduction of modulated genes, found through functional connections between immune and cellular pathways. Cytokine and chemokine analyses based on specific outcomes from the TNF-α and NF-κB signaling pathways revealed single, multi-strain and Lh-R0052-SLP specific attenuation of the majority of proteins measured (TNF-α, IL-8, CXCL1, CXCL2 and CXCL10), indicating potentially different mechanisms. These findings indicate a synergistic effect of the bacterial combinations relative to the single strain and Lh-R0052-SLP treatments in resolving toll-like receptor 3 (TLR3)-induced inflammation in IEC and maintaining cellular homeostasis, reinforcing the rationale for using multi-strain formulations as a probiotic. PMID:28099447

  12. Discrepancy between experimental and theoretical excitation transfer rates in LH2 bacteriochlorophyll-protein complexes of purple bacteria.

    PubMed

    Borisov, A Y

    2008-02-01

    Discrepancy is revealed between the values of excitation transfer times measured experimentally, and those calculated, for the atomic structures of B800 --> B850 bacteriochlorophylls within the LH2 light-harvesting pigment-protein complex of the purple bacterium Rhodopseudomonas acidophila. The value 2.9-3.2 ps for the B800 --> B850 excitation transfer, calculated on the basis of atomic structure of LH2, is about 4-times longer than that measured for this bacterium (0.7 ps). This discrepancy appears common in at least two purple bacteria. Possible sources responsible for this discrepancy are discussed. It may either signify some drawback/s/ in our notions about the precise in vivo structure of LH2 complexes, for example, possible changes of LH2 structure during crystallization, or it may reflect our ignorance of some mechanisms involved in excitation migration.

  13. Construction of hybrid photosynthetic units using peripheral and core antennae from two different species of photosynthetic bacteria: detection of the energy transfer from bacteriochlorophyll a in LH2 to bacteriochlorophyll b in LH1.

    PubMed

    Fujii, Ritsuko; Shimonaka, Shozo; Uchida, Naoko; Gardiner, Alastair T; Cogdell, Richard J; Sugisaki, Mitsuru; Hashimoto, Hideki

    2008-01-01

    Typical purple bacterial photosynthetic units consist of supra-molecular arrays of peripheral (LH2) and core (LH1-RC) antenna complexes. Recent atomic force microscopy pictures of photosynthetic units in intact membranes have revealed that the architecture of these units is variable (Scheuring et al. (2005) Biochim Bhiophys Acta 1712:109-127). In this study, we describe methods for the construction of heterologous photosynthetic units in lipid-bilayers from mixtures of purified LH2 (from Rhodopseudomonas acidophila) and LH1-RC (from Rhodopseudomonas viridis) core complexes. The architecture of these reconstituted photosynthetic units can be varied by controlling ratio of added LH2 to core complexes. The arrangement of the complexes was visualized by electron-microscopy in combination with Fourier analysis. The regular trigonal array of the core complexes seen in the native photosynthetic membrane could be regenerated in the reconstituted membranes by temperature cycling. In the presence of added LH2 complexes, this trigonal symmetry was replaced with orthorhombic symmetry. The small lattice lengths for the latter suggest that the constituent unit of the orthorhombic lattice is the LH2. Fluorescence and fluorescence-excitation spectroscopy was applied to the set of the reconstituted membranes prepared with various proportions of LH2 to core complexes. Remarkably, even though the LH2 complexes contain bacteriochlorophyll a, and the core complexes contain bacteriochlorophyll b, it was possible to demonstrate energy transfer from LH2 to the core complexes. These experiments provide a first step along the path toward investigating how changing the architecture of purple bacterial photosynthetic units affects the overall efficiency of light-harvesting.

  14. Heterogeneity of carotenoid content and composition in LH2 of the purple sulphur bacterium Allochromatium minutissimum grown under carotenoid-biosynthesis inhibition.

    PubMed

    Makhneva, Zoya; Bolshakov, Maksim; Moskalenko, Andrey

    2008-01-01

    The effects brought about by growing Allochromatium (Alc.) minutissimum in the presence of different concentrations of the carotenoid (Car) biosynthetic inhibitor diphenylamine (DPA) have been investigated. A decrease of Car content (from approximately 70% to >5%) in the membranes was accompanied by an increase of the percentage of (immature) Cars with reduced numbers of conjugated C=C bonds (from neurosporene to phytoene). Based on the obtained results and the analysis of literature data, the conclusion is reached that accumulation of phytoene during inhibition did not occur. Surprisingly, DPA inhibited phytoene synthase instead of phytoene desaturase as generally assumed. The distribution of Cars in peripheral antenna (LH2) complexes and their effect on the stability of LH2 has been investigated using absorption spectroscopy and HPLC analysis. Heterogeneity of Car composition and contents in the LH2 pool is revealed. The Car contents in LH2 varied widely from control levels to complete absence. According to common view, the assembly of LH2 occurs only in the presence of Cars. Here, we show that the LH2 can be assembled without any Cars. The presence of Cars, however, is important for structural stability of LH2 complexes.

  15. LH-21 and abnormal cannabidiol improve β-cell function in isolated human and mouse islets through GPR55-dependent and -independent signalling.

    PubMed

    Ruz-Maldonado, Inmaculada; Pingitore, Attilio; Liu, Bo; Atanes, Patricio; Huang, Guo Cai; Baker, David; Alonso, Francisco José; Bermúdez-Silva, Francisco Javier; Persaud, Shanta J

    2018-04-01

    To examine the effects of Abn-CBD (GPR55 agonist) and LH-21 (CB1 antagonist) on human and mouse islet function, and to determine signalling via GPR55 using islets from GPR55 -/- mice. Islets isolated from human organ donors and mice were incubated in the absence or presence of Abn-CBD or LH-21, and insulin secretion, [Ca 2+ ] i, cAMP , apoptosis, β-cell proliferation and CREB and AKT phosphorylation were examined using standard techniques. Abn-CBD potentiated glucose-stimulated insulin secretion and elevated [Ca 2+ ] i in human islets and islets from both GPR55 +/+ and GPR55 -/- mice. LH-21 also increased insulin secretion and [Ca 2+ ] i in human islets and GPR55 +/+ mouse islets, but concentrations of LH-21 up to 0.1 μM were ineffective in islets from GPR55 -/- mice. Neither ligand affected basal insulin secretion or islet cAMP levels. Abn-CBD and LH-21 reduced cytokine-induced apoptosis in human islets and GPR55 +/+ mouse islets, and these effects were suppressed after GPR55 deletion. They also increased β-cell proliferation: the effects of Abn-CBD were preserved in islets from GPR55 -/- mice, while those of LH-21 were abolished. Abn-CBD and LH-21 increased AKT phosphorylation in mouse and human islets. This study showed that Abn-CBD and LH-21 improve human and mouse islet β-cell function and viability. Use of islets from GPR55 -/- mice suggests that designation of Abn-CBD and LH-21 as a GPR55 agonist and a CB1 antagonist, should be revised. © 2017 John Wiley & Sons Ltd.

  16. Crystallization and preliminary X-ray diffraction analysis of the peripheral light-harvesting complex LH2 from Marichromatium purpuratum.

    PubMed

    Cranston, Laura J; Roszak, Aleksander W; Cogdell, Richard J

    2014-06-01

    LH2 from the purple photosynthetic bacterium Marichromatium (formerly known as Chromatium) purpuratum is an integral membrane pigment-protein complex that is involved in harvesting light energy and transferring it to the LH1-RC `core' complex. The purified LH2 complex was crystallized using the sitting-drop vapour-diffusion method at 294 K. The crystals diffracted to a resolution of 6 Å using synchrotron radiation and belonged to the tetragonal space group I4, with unit-cell parameters a=b=109.36, c=80.45 Å. The data appeared to be twinned, producing apparent diffraction symmetry I422. The tetragonal symmetry of the unit cell and diffraction for the crystals of the LH2 complex from this species reveal that this complex is an octamer.

  17. Crystallization and preliminary X-ray diffraction analysis of the peripheral light-harvesting complex LH2 from Marichromatium purpuratum

    PubMed Central

    Cranston, Laura J.; Roszak, Aleksander W.; Cogdell, Richard J.

    2014-01-01

    LH2 from the purple photosynthetic bacterium Marichromatium (formerly known as Chromatium) purpuratum is an integral membrane pigment–protein complex that is involved in harvesting light energy and transferring it to the LH1–RC ‘core’ complex. The purified LH2 complex was crystallized using the sitting-drop vapour-diffusion method at 294 K. The crystals diffracted to a resolution of 6 Å using synchrotron radiation and belonged to the tetragonal space group I4, with unit-cell parameters a = b = 109.36, c = 80.45 Å. The data appeared to be twinned, producing apparent diffraction symmetry I422. The tetragonal symmetry of the unit cell and diffraction for the crystals of the LH2 complex from this species reveal that this complex is an octamer. PMID:24915099

  18. Fluorescent chemosensor based on sensitive Schiff base for selective detection of Zn2+

    NASA Astrophysics Data System (ADS)

    Singh, T. Sanjoy; Paul, Pradip C.; Pramanik, Harun A. R.

    2014-03-01

    A Schiff-base fluorescent compound - N, N‧-bis(salicylidene)-1,2 - phenylenediamine (LH2) was synthesized and evaluated as a chemoselective Zn2+ sensor. Addition of Zn2+ to ethanol solution of LH2 resulted in a red shift with a pronounced enhancement in the fluorescence intensity. Moreover, other common alkali, alkaline earth and transition metal ions failed to induce response or minimal spectral changes. Notably, this chemosensor could distinguish clearly Zn2+ from Cd2+. Fluorescence studies on free Schiff base ligand LH2 and LH2 - Zn2+ complex reveal that the quantum yield strongly increases upon coordination. The stoichiometric ratio and association constant were evaluated using Benesi - Hildebrand relation giving 1:1 stoichiometry. This further corroborated 1:1 complex formation based on Job's plot analyses.

  19. Genetic analysis and fine mapping of LH1 and LH2, a set of complementary genes controlling late heading in rice (Oryza sativa L.)

    PubMed Central

    Liu, Shuang; Wang, Feng; Gao, Li Jun; Li, Jin Hua; Li, Rong Bai; Gao, Han Liang; Deng, Guo Fu; Yang, Jin Shui; Luo, Xiao Jin

    2012-01-01

    Heading date in rice (Oryza sativa L.) is a critical agronomic trait with a complex inheritance. To investigate the genetic basis and mechanism of gene interaction in heading date, we conducted genetic analysis on segregation populations derived from crosses among the indica cultivars Bo B, Yuefeng B and Baoxuan 2. A set of dominant complementary genes controlling late heading, designated LH1 and LH2, were detected by molecular marker mapping. Genetic analysis revealed that Baoxuan 2 contains both dominant genes, while Bo B and Yuefeng B each possess either LH1 or LH2. Using larger populations with segregant ratios of 3 : 1, we fine-mapped LH1 to a 63-kb region near the centromere of chromosome 7 flanked by markers RM5436 and RM8034, and LH2 to a 177-kb region on the short arm of chromosome 8 between flanking markers Indel22468-3 and RM25. Some candidate genes were identified through sequencing of Bo B and Yuefeng B in these target regions. Our work provides a solid foundation for further study on gene interaction in heading date and has application in marker-assisted breeding of photosensitive hybrid rice in China. PMID:23341744

  20. Genetic analysis and fine mapping of LH1 and LH2, a set of complementary genes controlling late heading in rice (Oryza sativa L.).

    PubMed

    Liu, Shuang; Wang, Feng; Gao, Li Jun; Li, Jin Hua; Li, Rong Bai; Gao, Han Liang; Deng, Guo Fu; Yang, Jin Shui; Luo, Xiao Jin

    2012-12-01

    Heading date in rice (Oryza sativa L.) is a critical agronomic trait with a complex inheritance. To investigate the genetic basis and mechanism of gene interaction in heading date, we conducted genetic analysis on segregation populations derived from crosses among the indica cultivars Bo B, Yuefeng B and Baoxuan 2. A set of dominant complementary genes controlling late heading, designated LH1 and LH2, were detected by molecular marker mapping. Genetic analysis revealed that Baoxuan 2 contains both dominant genes, while Bo B and Yuefeng B each possess either LH1 or LH2. Using larger populations with segregant ratios of 3 : 1, we fine-mapped LH1 to a 63-kb region near the centromere of chromosome 7 flanked by markers RM5436 and RM8034, and LH2 to a 177-kb region on the short arm of chromosome 8 between flanking markers Indel22468-3 and RM25. Some candidate genes were identified through sequencing of Bo B and Yuefeng B in these target regions. Our work provides a solid foundation for further study on gene interaction in heading date and has application in marker-assisted breeding of photosensitive hybrid rice in China.

  1. Transport dynamics in membranes of photosynthetic purple bacteria

    NASA Astrophysics Data System (ADS)

    Caycedo, Felipe; Rodriguez, Ferney; Quiroga, Luis; Fassioli, Francesca; Johnson, Neil

    2007-03-01

    Photo-Syntethic Unit (PSU) of purple bacteria is conformed by three basic constituents: Light Harvesting Complex 2 (LH2) antenna complexes, where chromophores are distributed in a ring in close contact with caroteniods with a function of collecting light; LH1s, ring shaped structures of chromophores which harvest and funnel excitations to the Reaction Centre (RC), where phtosynthesis takes place. Studies concerning a single PSU have been capable of reproducing experimental transfer times, but incapable of explaining the fact that architecture LH2-LH1-RC of phototosynthetic membranes changes as light intensity conditions vary. The organization of antenna complexes in the membranes that support PSU seems to have its own functionality. A hopping model where excitations are transferred within a membrane is used, and populations of RC, LH1 and LH2 are investigated. Different statistics concerning arrival times of excitations that excite a single PSU are considered and compared with the global model where coordinates of a great portion of a membrane are included. The model permits in a classical basis to understand which parameters make photosynthesis in purple bateria efficient and reliable.

  2. Spectral heterogeneity and carotenoid-to-bacteriochlorophyll energy transfer in LH2 light-harvesting complexes from Allochromatium vinosum.

    PubMed

    Magdaong, Nikki M; LaFountain, Amy M; Hacking, Kirsty; Niedzwiedzki, Dariusz M; Gibson, George N; Cogdell, Richard J; Frank, Harry A

    2016-02-01

    Photosynthetic organisms produce a vast array of spectral forms of antenna pigment-protein complexes to harvest solar energy and also to adapt to growth under the variable environmental conditions of light intensity, temperature, and nutrient availability. This behavior is exemplified by Allochromatium (Alc.) vinosum, a photosynthetic purple sulfur bacterium that produces different types of LH2 light-harvesting complexes in response to variations in growth conditions. In the present work, three different spectral forms of LH2 from Alc. vinosum, B800-820, B800-840, and B800-850, were isolated, purified, and examined using steady-state absorption and fluorescence spectroscopy, and ultrafast time-resolved absorption spectroscopy. The pigment composition of the LH2 complexes was analyzed by high-performance liquid chromatography, and all were found to contain five carotenoids: lycopene, anhydrorhodovibrin, spirilloxanthin, rhodopin, and rhodovibrin. Spectral reconstructions of the absorption and fluorescence excitation spectra based on the pigment composition revealed significantly more spectral heterogeneity in these systems compared to LH2 complexes isolated from other species of purple bacteria. The data also revealed the individual carotenoid-to-bacteriochlorophyll energy transfer efficiencies which were correlated with the kinetic data from the ultrafast transient absorption spectroscopic experiments. This series of LH2 complexes allows a systematic exploration of the factors that determine the spectral properties of the bound pigments and control the rate and efficiency of carotenoid-to-bacteriochlorophyll energy transfer.

  3. Estriol administration modulates luteinizing hormone secretion in women with functional hypothalamic amenorrhea.

    PubMed

    Genazzani, Alessandro D; Meczekalski, Blazej; Podfigurna-Stopa, Agnieszka; Santagni, Susanna; Rattighieri, Erica; Ricchieri, Federica; Chierchia, Elisa; Simoncini, Tommaso

    2012-02-01

    To evaluate the influence of estriol administration on the hypothalamus-pituitary function and gonadotropins secretion in patients affected by functional hypothalamic amenorrhea (FHA). Controlled clinical study. Patients with FHA in a clinical research environment. Twelve hypogonadotropic patients affected by FHA. Pulsatility study of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and a gonadotropin-releasing hormone (GnRH) test (10 μg in bolus) at baseline condition and after 8 weeks of therapy with 2 mg/day of estriol. Measurements of plasma LH, FSH, estradiol (E(2)), androstenedione (A), 17α-hydroxyprogesterone (17-OHP), cortisol, androstenedione (A), testosterone (T), thyroid-stimulating hormone (TSH), free triiodothyronine (fT(3)), free thyroxine (fT(4)), and insulin, and pulse detection. After treatment, the FHA patients showed a statistically significant increase of LH plasma levels (from 0.7 ± 0.1 mIU/mL to 3.5 ± 0.3 mIU/mL) and a statistically significant increase of LH pulse amplitude with no changes in LH pulse frequency. In addition, the LH response to the GnRH bolus was a statistically significant increase. Estriol administration induced the increase of LH plasma levels in FHA and improved GnRH-induced LH secretion. These findings suggest that estriol administration modulates the neuroendocrine control of the hypothalamus-pituitary unit and induces the recovery of LH synthesis and secretion in hypogonadotropic patients with FHA. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  4. Language function distribution in left-handers: A navigated transcranial magnetic stimulation study.

    PubMed

    Tussis, Lorena; Sollmann, Nico; Boeckh-Behrens, Tobias; Meyer, Bernhard; Krieg, Sandro M

    2016-02-01

    Recent studies suggest that in left-handers, the right hemisphere (RH) is more involved in language function when compared to right-handed subjects. Since data on lesion-based approaches is lacking, we aimed to investigate language distribution of left-handers by repetitive navigated transcranial magnetic stimulation (rTMS). Thus, rTMS was applied to the left hemisphere (LH) and RH in 15 healthy left-handers during an object-naming task, and resulting naming errors were categorized. Then, we calculated error rates (ERs=number of errors per number of stimulations) for both hemispheres separately and defined a laterality score as the quotient of the LH ER - RH ER through the LH ER + RH ER (abbreviated as (L-R)/(L+R)). In this context, (L-R)/(L+R)>0 indicates that the LH is dominant, whereas (L-R)/(L+R)<0 shows that the RH is dominant. No significant difference in ERs was found between hemispheres (all errors: mean LH 18.0±11.7%, mean RH 18.1±12.2%, p=0.94; all errors without hesitation: mean LH 12.4±9.8%, mean RH 12.9±10.0%, p=0.65; no responses: mean LH 9.3±9.2%, mean RH 11.5±10.3%, p=0.84). However, a significant difference between the results of (L-R)/(L+R) of left-handers and right-handers (source data of another study) for all errors (mean 0.01±0.14 vs. 0.19±0.20, p=0.0019) and all errors without hesitation (mean -0.02±0.20 vs. 0.19±0.28, p=0.0051) was revealed, whereas the comparison for no responses did not show a significant difference (mean: -0.004±0.27 vs. 0.09±0.44, p=0.64). Accordingly, left-handers present a comparatively equal language distribution across both hemispheres with language dominance being nearly equally distributed between hemispheres in contrast to right-handers. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Protein-induced geometric constraints and charge transfer in bacteriochlorophyll-histidine complexes in LH2.

    PubMed

    Wawrzyniak, Piotr K; Alia, A; Schaap, Roland G; Heemskerk, Mattijs M; de Groot, Huub J M; Buda, Francesco

    2008-12-14

    Bacteriochlorophyll-histidine complexes are ubiquitous in nature and are essential structural motifs supporting the conversion of solar energy into chemically useful compounds in a wide range of photosynthesis processes. A systematic density functional theory study of the NMR chemical shifts for histidine and for bacteriochlorophyll-a-histidine complexes in the light-harvesting complex II (LH2) is performed using the BLYP functional in combination with the 6-311++G(d,p) basis set. The computed chemical shift patterns are consistent with available experimental data for positive and neutral(tau) (N(tau) protonated) crystalline histidines. The results for the bacteriochlorophyll-a-histidine complexes in LH2 provide evidence that the protein environment is stabilizing the histidine close to the Mg ion, thereby inducing a large charge transfer of approximately 0.5 electronic equivalent. Due to this protein-induced geometric constraint, the Mg-coordinated histidine in LH2 appears to be in a frustrated state very different from the formal neutral(pi) (N(pi) protonated) form. This finding could be important for the understanding of basic functional mechanisms involved in tuning the electronic properties and exciton coupling in LH2.

  6. Lysyl Hydroxylase 2 Is Secreted by Tumor Cells and Can Modify Collagen in the Extracellular Space.

    PubMed

    Chen, Yulong; Guo, Houfu; Terajima, Masahiko; Banerjee, Priyam; Liu, Xin; Yu, Jiang; Momin, Amin A; Katayama, Hiroyuki; Hanash, Samir M; Burns, Alan R; Fields, Gregg B; Yamauchi, Mitsuo; Kurie, Jonathan M

    2016-12-09

    Lysyl hydroxylase 2 (LH2) catalyzes the hydroxylation of lysine residues in the telopeptides of fibrillar collagens, which leads to the formation of stable collagen cross-links. Recently we reported that LH2 enhances the metastatic propensity of lung cancer by increasing the amount of stable hydroxylysine aldehyde-derived collagen cross-links (HLCCs), which generate a stiffer tumor stroma (Chen, Y., et al. (2015) J. Clin. Invest. 125, 125, 1147-1162). It is generally accepted that LH2 modifies procollagen α chains on the endoplasmic reticulum before the formation of triple helical procollagen molecules. Herein, we report that LH2 is also secreted and modifies collagen in the extracellular space. Analyses of lung cancer cell lines demonstrated that LH2 is present in the cell lysates and the conditioned media in a dimeric, active form in both compartments. LH2 co-localized with collagen fibrils in the extracellular space in human lung cancer specimens and in orthotopic lung tumors generated by injection of a LH2-expressing human lung cancer cell line into nude mice. LH2 depletion in MC3T3 osteoblastic cells impaired the formation of HLCCs, resulting in an increase in the unmodified lysine aldehyde-derived collagen cross-link (LCC), and the addition of recombinant LH2 to the media of LH2-deficient MC3T3 cells was sufficient to rescue HLCC formation in the extracellular matrix. The finding that LH2 modifies collagen in the extracellular space challenges the current view that LH2 functions solely on the endoplasmic reticulum and could also have important implications for cancer biology. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Lysyl Hydroxylase 2 Is Secreted by Tumor Cells and Can Modify Collagen in the Extracellular Space*

    PubMed Central

    Chen, Yulong; Guo, Houfu; Terajima, Masahiko; Banerjee, Priyam; Liu, Xin; Yu, Jiang; Momin, Amin A.; Katayama, Hiroyuki; Hanash, Samir M.; Burns, Alan R.; Fields, Gregg B.; Yamauchi, Mitsuo; Kurie, Jonathan M.

    2016-01-01

    Lysyl hydroxylase 2 (LH2) catalyzes the hydroxylation of lysine residues in the telopeptides of fibrillar collagens, which leads to the formation of stable collagen cross-links. Recently we reported that LH2 enhances the metastatic propensity of lung cancer by increasing the amount of stable hydroxylysine aldehyde-derived collagen cross-links (HLCCs), which generate a stiffer tumor stroma (Chen, Y., et al. (2015) J. Clin. Invest. 125, 125, 1147–1162). It is generally accepted that LH2 modifies procollagen α chains on the endoplasmic reticulum before the formation of triple helical procollagen molecules. Herein, we report that LH2 is also secreted and modifies collagen in the extracellular space. Analyses of lung cancer cell lines demonstrated that LH2 is present in the cell lysates and the conditioned media in a dimeric, active form in both compartments. LH2 co-localized with collagen fibrils in the extracellular space in human lung cancer specimens and in orthotopic lung tumors generated by injection of a LH2-expressing human lung cancer cell line into nude mice. LH2 depletion in MC3T3 osteoblastic cells impaired the formation of HLCCs, resulting in an increase in the unmodified lysine aldehyde-derived collagen cross-link (LCC), and the addition of recombinant LH2 to the media of LH2-deficient MC3T3 cells was sufficient to rescue HLCC formation in the extracellular matrix. The finding that LH2 modifies collagen in the extracellular space challenges the current view that LH2 functions solely on the endoplasmic reticulum and could also have important implications for cancer biology. PMID:27803159

  8. Ground-State Electronic Structure of RC-LH1 and LH2 Pigment Assemblies of Purple Bacteria via the EBF-MO Method.

    PubMed

    Shrestha, Kushal; Jakubikova, Elena

    2015-08-20

    Light-harvesting antennas are protein-pigment complexes that play a crucial role in natural photosynthesis. The antenna complexes absorb light and transfer energy to photosynthetic reaction centers where charge separation occurs. This work focuses on computational studies of the electronic structure of the pigment networks of light-harvesting complex I (LH1), LH1 with the reaction center (RC-LH1), and light-harvesting complex II (LH2) found in purple bacteria. As the pigment networks of LH1, RC-LH1, and LH2 contain thousands of atoms, conventional density functional theory (DFT) and ab initio calculations of these systems are not computationally feasible. Therefore, we utilize DFT in conjunction with the energy-based fragmentation with molecular orbitals method and a semiempirical approach employing the extended Hückel model Hamiltonian to determine the electronic properties of these pigment assemblies. Our calculations provide a deeper understanding of the electronic structure of natural light-harvesting complexes, especially their pigment networks, which could assist in rational design of artificial photosynthetic devices.

  9. Study of the bacterial diversity of foods: PCR-DGGE versus LH-PCR.

    PubMed

    Garofalo, Cristiana; Bancalari, Elena; Milanović, Vesna; Cardinali, Federica; Osimani, Andrea; Sardaro, Maria Luisa Savo; Bottari, Benedetta; Bernini, Valentina; Aquilanti, Lucia; Clementi, Francesca; Neviani, Erasmo; Gatti, Monica

    2017-02-02

    The present study compared two culture-independent methods, polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE) and length-heterogeneity polymerase chain reaction (LH-PCR), for their ability to reveal food bacterial microbiota. Total microbial DNA and RNA were extracted directly from fourteen fermented and unfermented foods, and domain A of the variable regions V1 and V2 of the 16S rRNA gene was analyzed through LH-PCR and PCR-DGGE. Finally, the outline of these analyses was compared with bacterial viable counts obtained after bacterial growth on suitable selective media. For the majority of the samples, RNA-based PCR-DGGE revealed species that the DNA-based PCR-DGGE was not able to highlight. When analyzing either DNA or RNA, LH-PCR identified several lactic acid bacteria (LAB) and coagulase negative cocci (CCN) species that were not identified by PCR-DGGE. This phenomenon was particularly evident in food samples with viable loads<5.0 Logcfug -1 . Furthermore, LH-PCR was able to detect a higher number of peaks in the analyzed food matrices relative to species identified by PCR-DGGE. In light of these findings, it may be suggested that LH-PCR shows greater sensitivity than PCR-DGGE. However, PCR-DGGE detected some other species (LAB included) that were not detected by LH-PCR. Therefore, certain LH-PCR peaks not attributed to known species within the LH-PCR database could be solved by comparing them with species identified by PCR-DGGE. Overall, this study also showed that LH-PCR is a promising method for use in the food microbiology field, indicating the necessity to expand the LH-PCR database, which is based, up to now, mainly on LAB isolates from dairy products. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. FKBP65-dependent peptidyl-prolyl isomerase activity potentiates the lysyl hydroxylase 2-driven collagen cross-link switch.

    PubMed

    Chen, Yulong; Terajima, Masahiko; Banerjee, Priyam; Guo, Houfu; Liu, Xin; Yu, Jiang; Yamauchi, Mitsuo; Kurie, Jonathan M

    2017-04-05

    Bruck Syndrome is a connective tissue disease associated with inactivating mutations in lysyl hydroxylase 2 (LH2/PLOD2) or FK506 binding protein 65 (FKBP65/FKBP10). However, the functional relationship between LH2 and FKBP65 remains unclear. Here, we postulated that peptidyl prolyl isomerase (PPIase) activity of FKBP65 positively modulates LH2 enzymatic activity and is critical for the formation of hydroxylysine-aldehyde derived intermolecular collagen cross-links (HLCCs). To test this hypothesis, we analyzed collagen cross-links in Fkbp10-null and -wild-type murine embryonic fibroblasts. Although LH2 protein levels did not change, FKBP65 deficiency significantly diminished HLCCs and increased the non-hydroxylated lysine-aldehyde-derived collagen cross-links (LCCs), a pattern consistent with loss of LH2 enzymatic activity. The HLCC-to-LCC ratio was rescued in FKBP65-deficient murine embryonic fibroblasts by reconstitution with wild-type but not mutant FKBP65 that lacks intact PPIase domains. Findings from co-immunoprecipitation, protein-fragment complementation, and co-immunofluorescence assays showed that LH2 and FKBP65 are part of a common protein complex. We conclude that FKBP65 regulates LH2-mediated collagen cross-linking. Because LH2 promotes fibrosis and cancer metastasis, our findings suggest that pharmacologic strategies to target FKBP65 and LH2 may have complementary therapeutic activities.

  11. FKBP65-dependent peptidyl-prolyl isomerase activity potentiates the lysyl hydroxylase 2-driven collagen cross-link switch

    PubMed Central

    Chen, Yulong; Terajima, Masahiko; Banerjee, Priyam; Guo, Houfu; Liu, Xin; Yu, Jiang; Yamauchi, Mitsuo; Kurie, Jonathan M.

    2017-01-01

    Bruck Syndrome is a connective tissue disease associated with inactivating mutations in lysyl hydroxylase 2 (LH2/PLOD2) or FK506 binding protein 65 (FKBP65/FKBP10). However, the functional relationship between LH2 and FKBP65 remains unclear. Here, we postulated that peptidyl prolyl isomerase (PPIase) activity of FKBP65 positively modulates LH2 enzymatic activity and is critical for the formation of hydroxylysine-aldehyde derived intermolecular collagen cross-links (HLCCs). To test this hypothesis, we analyzed collagen cross-links in Fkbp10-null and –wild-type murine embryonic fibroblasts. Although LH2 protein levels did not change, FKBP65 deficiency significantly diminished HLCCs and increased the non-hydroxylated lysine-aldehyde–derived collagen cross-links (LCCs), a pattern consistent with loss of LH2 enzymatic activity. The HLCC-to-LCC ratio was rescued in FKBP65-deficient murine embryonic fibroblasts by reconstitution with wild-type but not mutant FKBP65 that lacks intact PPIase domains. Findings from co-immunoprecipitation, protein-fragment complementation, and co-immunofluorescence assays showed that LH2 and FKBP65 are part of a common protein complex. We conclude that FKBP65 regulates LH2-mediated collagen cross-linking. Because LH2 promotes fibrosis and cancer metastasis, our findings suggest that pharmacologic strategies to target FKBP65 and LH2 may have complementary therapeutic activities. PMID:28378777

  12. Functional hypothalamic amenorrhea: current view on neuroendocrine aberrations.

    PubMed

    Meczekalski, Blazej; Podfigurna-Stopa, Agnieszka; Warenik-Szymankiewicz, Alina; Genazzani, Andrea Riccardo

    2008-01-01

    Functional hypothalamic amenorrhea (FHA) is defined as a non-organic and reversible disorder in which the impairment of gonadotropin-releasing hormone (GnRH) pulsatile secretion plays a key role. There are main three types of FHA: stress-related amenorrhea, weight loss-related amenorrhea and exercise-related amenorrhea. The spectrum of GnRH-luteinizing hormone (LH) disturbances in FHA is very broad and includes lower mean frequency of LH pulses, complete absence of LH pulsatility, normal-appearing secretion pattern and higher mean frequency of LH pulses. Precise mechanisms underlying the pathophysiology of FHA are very complex and unclear. Numerous neuropeptides, neurotransmitters and neurosteroids play important roles in the physiological regulation of GnRH pulsatile secretion and there is evidence that different neuropeptides may be involved in the pathophysiology of FHA. Particular attention is paid to such substances as allopregnanolone, neuropeptide Y, corticotropin-releasing hormone, leptin, ghrelin and beta-endorphin. Some studies reveal significant changes in these mentioned substances in patients with FHA. There are also speculations about use some of these substances or their antagonists in the treatment of FHA.

  13. Fine tuning of the spectral properties of LH2 by single amino acid residues.

    PubMed

    Silber, Martina V; Gabriel, Günther; Strohmann, Brigitte; Garcia-Martin, Adela; Robert, Bruno; Braun, Paula

    2008-05-01

    The peripheral light-harvesting complex, LH2, of Rhodobacter sphaeroides consists of an assembly of membrane-spanning alpha and beta polypeptides which assemble the photoactive bacteriochlorophyll and carotenoid molecules. In this study we systematically investigated bacteriochlorophyll-protein interactions and their effect on functional bacteriochlorophyll assembly by site-directed mutations of the LH2 alpha-subunit. The amino acid residues, isoleucine at position -1 and serine at position -4 were replaced by 12 and 13 other residues, respectively. All residues replacing isoleucine at position -1 supported the functional assembly of LH2. The replacement of isoleucine by glycine, glutamine or asparagine, however, produced LH2 complex with significantly altered spectral properties in comparison to LH2 WT. As indicated by resonance Raman spectroscopy extensive rearrangement of the bacteriochlorophyll-B850 macrocycle(s) took place in LH2 in which isoleucine -1 was replaced by glycine. The replacement results in disruption of the H-bond between the C3 acetyl groups and the aromatic residues +13/+14 without affecting the H-bond involving the C13(1) keto group. In contrast, nearly all amino acid replacements of serine at position -4 resulted in shifting of the bacteriochlorophyll-B850 red most absorption maximum. Interestingly, the extent of shifting closely correlated with the volume of the residue at position -4. These results illustrate that fine tuning of the spectral properties of the bacteriochlorophyll-B850 molecules depend on their packing with single amino acid residues at distinct positions.

  14. Understanding the compaction behaviour of low-substituted HPC: macro, micro, and nano-metric evaluations.

    PubMed

    ElShaer, Amr; Al-Khattawi, Ali; Mohammed, Afzal R; Warzecha, Monika; Lamprou, Dimitrios A; Hassanin, Hany

    2018-06-01

    The fast development in materials science has resulted in the emergence of new pharmaceutical materials with superior physical and mechanical properties. Low-substituted hydroxypropyl cellulose is an ether derivative of cellulose and is praised for its multi-functionality as a binder, disintegrant, film coating agent and as a suitable material for medical dressings. Nevertheless, very little is known about the compaction behaviour of this polymer. The aim of the current study was to evaluate the compaction and disintegration behaviour of four grades of L-HPC namely; LH32, LH21, LH11, and LHB1. The macrometric properties of the four powders were studied and the compaction behaviour was evaluated using the out-of-die method. LH11 and LH22 showed poor flow properties as the powders were dominated by fibrous particles with high aspect ratios, which reduced the powder flow. LH32 showed a weak compressibility profile and demonstrated a large elastic region, making it harder for this polymer to deform plastically. These findings are supported by AFM which revealed the high roughness of LH32 powder (100.09 ± 18.84 nm), resulting in small area of contact, but promoting mechanical interlocking. On the contrary, LH21 and LH11 powders had smooth surfaces which enabled larger contact area and higher adhesion forces of 21.01 ± 11.35 nN and 9.50 ± 5.78 nN, respectively. This promoted bond formation during compression as LH21 and LH11 powders had low strength yield.

  15. LH and hCG Action on the Same Receptor Results in Quantitatively and Qualitatively Different Intracellular Signalling

    PubMed Central

    Casarini, Livio; Lispi, Monica; Longobardi, Salvatore; Milosa, Fabiola; La Marca, Antonio; Tagliasacchi, Daniela; Pignatti, Elisa; Simoni, Manuela

    2012-01-01

    Human luteinizing hormone (hLH) and chorionic gonadotropin (hCG) act on the same receptor (LHCGR) but it is not known whether they elicit the same cellular and molecular response. This study compares for the first time the activation of cell-signalling pathways and gene expression in response to hLH and hCG. Using recombinant hLH and recombinant hCG we evaluated the kinetics of cAMP production in COS-7 and hGL5 cells permanently expressing LHCGR (COS-7/LHCGR, hGL5/LHCGR), as well as cAMP, ERK1/2, AKT activation and progesterone production in primary human granulosa cells (hGLC). The expression of selected target genes was measured in the presence or absence of ERK- or AKT-pathways inhibitors. In COS-7/LHCGR cells, hCG is 5-fold more potent than hLH (cAMP ED50: 107.1±14.3 pM and 530.0±51.2 pM, respectively). hLH maximal effect was significantly faster (10 minutes by hLH; 1 hour by hCG). In hGLC continuous exposure to equipotent doses of gonadotropins up to 36 hours revealed that intracellular cAMP production is oscillating and significantly higher by hCG versus hLH. Conversely, phospho-ERK1/2 and -AKT activation was more potent and sustained by hLH versus hCG. ERK1/2 and AKT inhibition removed the inhibitory effect on NRG1 (neuregulin) expression by hLH but not by hCG; ERK1/2 inhibition significantly increased hLH- but not hCG-stimulated CYP19A1 (aromatase) expression. We conclude that: i) hCG is more potent on cAMP production, while hLH is more potent on ERK and AKT activation; ii) hGLC respond to equipotent, constant hLH or hCG stimulation with a fluctuating cAMP production and progressive progesterone secretion; and iii) the expression of hLH and hCG target genes partly involves the activation of different pathways depending on the ligand. Therefore, the LHCGR is able to differentiate the activity of hLH and hCG. PMID:23071612

  16. Peripheral Light-Harvesting LH2 Complex Can Be Assembled in Cells of Nonsulfur Purple Bacterium Rhodoblastus acidophilus without Carotenoids.

    PubMed

    Bol'shakov, M A; Ashikhmin, A A; Makhneva, Z K; Moskalenko, A A

    2015-09-01

    The effect of carotenoids on the assembly of LH2 complex in cells of the purple nonsulfur bacterium Rhodoblastus acidophilus was investigated. For this purpose, the bacterial culture was cultivated with an inhibitor of carotenoid biosynthesis - 71 µM diphenylamine (DPA). The inhibitor decreased the level of biosynthesis of the colored carotenoids in membranes by ~58%. It was found that a large amount of phytoene was accumulated in them. This carotenoid precursor was bound nonspecifically to LH2 complex and did not stabilize its structure. Thermostability testing of the isolated LH2 complex together with analysis of carotenoid composition revealed that the population of this complex was heterogeneous with respect to carotenoid composition. One fraction of the LH2 complex with carotenoid content around 90% remains stable and was not destroyed under heating for 15 min at 50°C. The other fraction of LH2 complex containing on average less than one molecule of carotenoid per complex was destroyed under heating, forming a zone of free pigments (and polypeptides). The data suggest that a certain part of the LH2 complexes is assembled without carotenoids in cells of the nonsulfur bacterium Rbl. acidophilus grown with DPA. These data contradict the fact that the LH2 complex from nonsulfur bacteria cannot be assembled without carotenoids, but on the other hand, they are in good agreement with the results demonstrated in our earlier studies of the sulfur bacteria Allochromatium minutissimum and Ectothiorhodospira haloalkaliphila. Carotenoidless LH2 complex was obtained from these bacteria with the use of DPA (Moskalenko, A. A., and Makhneva, Z. K. (2012) J. Photochem. Photobiol., 108, 1-7; Ashikhmin, A., et al. (2014) Photosynth. Res., 119, 291-303).

  17. Ghrelin fibers from lateral hypothalamus project to nucleus tractus solitaries and are involved in gastric motility regulation in cisplatin-treated rats.

    PubMed

    Gong, Yanling; Liu, Yang; Liu, Fei; Wang, Shasha; Jin, Hong; Guo, Feifei; Xu, Luo

    2017-03-15

    Ghrelin can alleviate cancer chemotherapy-induced dyspepsia in rodents, though the neural mechanisms involved are not known. Therefore, ghrelin projections from the lateral hypothalamus (LH) and its involvement in the regulation of gastric motility in cisplatin-treated rats were investigated with a multi-disciplined approach. Retrograde tracing combined with fluoro-immunohistochemical staining were used to investigate ghrelin fiber projections arising from LH and projecting to nucleus tractus solitaries (NTS). Results revealed that ghrelin fibers originating in LH project to NTS. Expression of ghrelin and its receptor growth hormone secretagogue receptor (GHS-R1a) in LH and NTS were detected by Western Blot. 2days after cisplatin dosing, expression of ghrelin in LH decreased while GHS-R1a in both LH and NTS increased. In electrophysiological experiments, the effects of N-methyl-d-aspartate (NMDA) microinjection in LH on neuronal discharge of gastric distension-responsive neurons in NTS and gastric motility were assessed. NMDA in LH excited most of ghrelin-responsive gastric distension (GD)-sensitive neurons in NTS and promoted gastric motility. This effect was partially blocked by ghrelin antibody in NTS. Furthermore, the excitatory effects of NMDA in cisplatin-treated rats were weaker than those in saline-treated rats. Behaviorally, cisplatin induced a significant increase of kaolin consumption and decrease of food intake. These studies reveal a decreased expression of ghrelin in LH and up-regulation of GHS-R1a in LH and NTS, which are involved in the regulation of GD neuronal discharge in NTS and gastric motility. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Atomic force microscopy reveals multiple patterns of antenna organization in purple bacteria: implications for energy transduction mechanisms and membrane modeling.

    PubMed

    Sturgis, James N; Niederman, Robert A

    2008-01-01

    Recent topographs of the intracytoplasmic membrane (ICM) of purple bacteria obtained by atomic force microscopy (AFM) have provided the first surface views of the native architecture of a multicomponent biological membrane at submolecular resolution, representing an important landmark in structural biology. A variety of species-dependent, closely packed arrangements of light-harvesting (LH) complexes was revealed: the most highly organized was found in Rhodobacter sphaeroides in which the peripheral LH2 antenna was seen either in large clusters or in fixed rows interspersed among ordered arrays of dimeric LH1-reaction center (RC) core complexes. A more random organization was observed in other species containing both the LH1 and LH2 complexes, as typified by Rhododspirillum photometricum with randomly packed monomeric LH1-RC core complexes intermingled with large, paracrystalline domains of LH2 antenna. Surprisingly, no structures that could be identified as the ATP synthase or cytochrome bc (1) complexes were observed, which may reflect their localization at ICM vesicle poles or in curved membrane areas, out of view from the flat regions imaged by AFM. This possible arrangement of energy transducing complexes has required a reassessment of energy tranduction mechanisms which place the cytochrome bc (1) complex in close association with the RC. Instead, more plausible proposals must account for the movement of quinone redox species over considerable membrane distances on appropriate time scales. AFM, together with atomic resolution structures are also providing the basis for molecular modeling of the ICM that is leading to an improved picture of the supramolecular organization of photosynthetic complexes, as well as the forces that drive their segregation into distinct domains.

  19. Developmental programming: Prenatal BPA treatment disrupts timing of LH surge and ovarian follicular wave dynamics in adult sheep

    PubMed Central

    Veiga-Lopez, A; Beckett, EM; Abi Salloum, B; Ye, W; Padmanabhan, V

    2014-01-01

    Developmental exposure to BPA adversely affects reproductive function. In sheep, prenatal BPA treatment induces reproductive neuroendocrine defects, manifested as LH excess and dampened LH surge and perturbs early ovarian gene expression. In this study we hypothesized that prenatal BPA treatment will also disrupt ovarian follicular dynamics. Pregnant sheep were treated from days 30 to 90 of gestation with 3 different BPA doses (0.05, 0.5, or 5 mg/kg BW/day). All female offspring were estrus synchronized and transrectal ultrasonography was performed daily for 22 days to monitor ovarian follicular and corpora lutea dynamics. Blood samples were collected to assess hormonal preovulatory changes and luteal progesterone dynamics. Statistical analysis revealed that the time interval between the estradiol rise and the preovulatory LH surge was shortened in the BPA-treated females. None of the three BPA doses had an effect on corpora lutea, progestogenic cycles, and mean or duration of ovulatory and non-ovulatory follicles. However, differences in follicular count trajectories were evident in all three follicular size classes (2–3 mm, 4–5 mm, and ≥ 6 mm) of prenatal BPA-treated animals compared to controls. Number of follicular waves tended also to be more variable in the prenatal BPA-treated groups ranging from 2 to 5 follicular waves per cycle, while this was restricted to 3 to 4 waves in control females. These changes in ovarian follicular dynamics coupled with defects in time interval between estradiol rise and preovulatory LH release are likely to lead to subfertility in prenatal BPA-treated females. PMID:24923655

  20. Kisspeptin and LH pulsatile temporal coupling in PCOS patients.

    PubMed

    Katulski, Krzysztof; Podfigurna, Agnieszka; Czyzyk, Adam; Meczekalski, Blazej; Genazzani, Alessandro D

    2018-05-04

    To evaluate the temporal coupling between spontaneous kisspeptin and luteinizing hormone (LH) pulsatile releases in polycystic ovary syndrome (PCOS) patients. We examined 71 patients diagnosed with PCOS. A 2 h pulsatility study was performed to evaluate serum kisspeptin and LH pulse frequency and concentration, sampled every 10 min; baseline follicle-stimulating hormone (FSH), estradiol (E2), prolactin (PRL), cortisol, 17-hydroksy-progesterone (17OHP), testosterone (T), free testosterone index (FTI, and insulin levels were also measured. Detect and Specific Concordance (SC) algorithms were used to evaluate the temporal coupling associations between spontaneous episodic secretion of kisspeptin and LH. All PCOS patients demonstrated LH and kisspeptin pulsatile secretions. When the SC index was calculated across the sample of PCOS patients (n = 71), no temporal coupling was observed between kisspeptin and LH pulses. When PCOS patients were subdivided according to their menstrual cyclicity, oligomenorrheic patients demonstrated elevated kisspeptin pulse frequency. Additionally, the SC index reveled a temporal coupling between kisspeptin and LH secretory peaks only in eumenorrheic patients (n = 30, intermenstrual interval < 45 days). Oligomenorrheic PCOS patients (intermenstrual interval > 45 days) did not demonstrate temporal coupling between kisspeptin and LH secretory peaks. The study of the endogenous kisspeptin and LH pulsatile release revealed the temporal coupling of kisspeptin with LH secretory pulses only in eumenorrheic. This data supports the hypothesis that neuroendocrine impairments in PCOS affect the coupling of kisspeptin with LH pulses and potentially worsen as the disease progresses, becoming unequivocally evident in oligomenorrheic PCOS patients.

  1. Developmental programming: impact of prenatal testosterone excess on pre- and postnatal gonadotropin regulation in sheep.

    PubMed

    Manikkam, Mohan; Thompson, Robert C; Herkimer, Carol; Welch, Kathleen B; Flak, Jonathan; Karsch, Fred J; Padmanabhan, Vasantha

    2008-04-01

    The goal of this study was to explore mechanisms that mediate hypersecretion of LH and progressive loss of cyclicity in female sheep exposed during fetal life to excess testosterone. Our working hypothesis was that prenatal testosterone excess, by its androgenic action, amplifies GnRH-induced LH (but not FSH) secretion and, thus, hypersecretion of LH in adulthood, and that this results from altered developmental gene expression of GnRH and estradiol (E2) receptors, gonadotropin subunits, and paracrine factors that differentially regulate LH and FSH synthesis. We observed that, relative to controls, females exposed during fetal life to excess testosterone, as well as the nor-aromatizable androgen dihydrotestosterone, exhibited enhanced LH but not FSH responses to intermittent delivery of GnRH boluses under conditions in which endogenous LH (GnRH) pulses were suppressed. Luteinizing hormone hypersecretion was more evident in adults than in prepubertal females, and it was associated with development of acyclicity. Measurement of pituitary mRNA concentrations revealed that prenatal testosterone excess induced developmental changes in gene expression of pituitary GnRH and E2 receptors and paracrine modulators of LH and FSH synthesis in a manner consistent with subsequent amplification of LH release. Together, this series of studies suggests that prenatal testosterone excess, by its androgenic action, amplifies GnRH-induced LH response, leading to LH hypersecretion and acyclicity in adulthood, and that this programming involves developmental changes in expression of pituitary genes involved in LH and FSH release.

  2. Loss of microRNA-7a2 induces hypogonadotropic hypogonadism and infertility

    PubMed Central

    Ahmed, Kashan; LaPierre, Mary P.; Denzler, Rémy; Yang, Yinjie; Rülicke, Thomas; Latreille, Mathieu

    2017-01-01

    MicroRNAs (miRNAs) are negative modulators of gene expression that fine-tune numerous biological processes. miRNA loss-of-function rarely results in highly penetrant phenotypes, but rather, influences cellular responses to physiologic and pathophysiologic stresses. Here, we have reported that a single member of the evolutionarily conserved miR-7 family, miR-7a2, is essential for normal pituitary development and hypothalamic-pituitary-gonadal (HPG) function in adulthood. Genetic deletion of mir-7a2 causes infertility, with low levels of gonadotropic and sex steroid hormones, small testes or ovaries, impaired spermatogenesis, and lack of ovulation in male and female mice, respectively. We found that miR-7a2 is highly expressed in the pituitary, where it suppresses golgi glycoprotein 1 (GLG1) expression and downstream bone morphogenetic protein 4 (BMP4) signaling and also reduces expression of the prostaglandin F2a receptor negative regulator (PTGFRN), an inhibitor of prostaglandin signaling and follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretion. Our results reveal that miR-7a2 critically regulates sexual maturation and reproductive function by interconnecting miR-7 genomic circuits that regulate FSH and LH synthesis and secretion through their effects on pituitary prostaglandin and BMP4 signaling. PMID:28218624

  3. The electronically excited states of LH2 complexes from Rhodopseudomonas acidophila strain 10050 studied by time-resolved spectroscopy and dynamic Monte Carlo simulations. I. Isolated, non-interacting LH2 complexes.

    PubMed

    Pflock, Tobias J; Oellerich, Silke; Southall, June; Cogdell, Richard J; Ullmann, G Matthias; Köhler, Jürgen

    2011-07-21

    We have employed time-resolved spectroscopy on the picosecond time scale in combination with dynamic Monte Carlo simulations to investigate the photophysical properties of light-harvesting 2 (LH2) complexes from the purple photosynthetic bacterium Rhodopseudomonas acidophila. The variations of the fluorescence transients were studied as a function of the excitation fluence, the repetition rate of the excitation and the sample preparation conditions. Here we present the results obtained on detergent solubilized LH2 complexes, i.e., avoiding intercomplex interactions, and show that a simple four-state model is sufficient to grasp the experimental observations quantitatively without the need for any free parameters. This approach allows us to obtain a quantitative measure for the singlet-triplet annihilation rate in isolated, noninteracting LH2 complexes.

  4. Unattended facial expressions asymmetrically bias the concurrent processing of nonemotional information.

    PubMed

    Maxwell, Jeffrey S; Shackman, Alexander J; Davidson, Richard J

    2005-09-01

    Planned and reflexive behaviors often occur in the presence of emotional stimuli and within the context of an individual's acute emotional state. Therefore, determining the manner in which emotion and attention interact is an important step toward understanding how we function in the real world. Participants in the current investigation viewed centrally displayed, task-irrelevant, face distractors (angry, neutral, happy) while performing a lateralized go/no-go continuous performance task. Lateralized go targets and no-go lures that did not spatially overlap with the faces were employed to differentially probe processing in the left (LH) and right (RH) cerebral hemispheres. There was a significant interaction between expression and hemisphere, with an overall pattern such that angry distractors were associated with relatively more RH inhibitory errors than neutral or happy distractors and happy distractors with relatively more LH inhibitory errors than angry or neutral distractors. Simple effects analyses confirmed that angry faces differentially interfered with RH relative to LH inhibition and with inhibition in the RH relative to happy faces. A significant three-way interaction further revealed that state anxiety moderated relations between emotional expression and hemisphere. Under conditions of low cognitive load, more intense anxiety was associated with relatively greater RH than LH impairment in the presence of both happy and threatening distractors. By contrast, under high load, only angry distractors produced greater RH than LH interference as a function of anxiety.

  5. Research Resource: Preovulatory LH Surge Effects on Follicular Theca and Granulosa Transcriptomes

    PubMed Central

    Gunewardena, Sumedha; Hong, Xiaoman; Spitschak, Marion; Baufeld, Anja

    2013-01-01

    The molecular mechanisms that regulate the pivotal transformation processes observed in the follicular wall following the preovulatory LH surge, are still not established, particularly for cells of the thecal layer. To elucidate thecal cell (TC) and granulosa cell (GC) type-specific biologic functions and signaling pathways, large dominant bovine follicles were collected before and 21 hours after an exogenous GnRH-induced LH surge. Antral GCs (aGCs; aspirated by follicular puncture) and membrane-associated GCs (mGCs; scraped from the follicular wall) were compared with TC expression profiles determined by mRNA microarrays. Of the approximately 11 000 total genes expressed in the periovulatory follicle, only 2% of thecal vs 25% of the granulosa genes changed in response to the LH surge. The majority of the 203 LH-regulated thecal genes were also LH regulated in GCs, leaving a total of 57 genes as LH-regulated TC-specific genes. Of the 57 thecal-specific LH-regulated genes, 74% were down-regulated including CYP17A1 and NR5A1, whereas most other genes are being identified for the first time within theca. Many of the newly identified up-regulated thecal genes (eg, PTX3, RND3, PPP4R4) were also up-regulated in granulosa. Minimal expression differences were observed between aGCs and mGCs; however, transcripts encoding extracellular proteins (NID2) and matrix modulators (ADAMTS1, SASH1) dominated these differences. We also identified large numbers of unknown LH-regulated GC genes and discuss their putative roles in ovarian function. This Research Resource provides an easy-to-access global evaluation of LH regulation in TCs and GCs that implicates numerous molecular pathways heretofore unknown within the follicle. PMID:23716604

  6. Research resource: preovulatory LH surge effects on follicular theca and granulosa transcriptomes.

    PubMed

    Christenson, Lane K; Gunewardena, Sumedha; Hong, Xiaoman; Spitschak, Marion; Baufeld, Anja; Vanselow, Jens

    2013-07-01

    The molecular mechanisms that regulate the pivotal transformation processes observed in the follicular wall following the preovulatory LH surge, are still not established, particularly for cells of the thecal layer. To elucidate thecal cell (TC) and granulosa cell (GC) type-specific biologic functions and signaling pathways, large dominant bovine follicles were collected before and 21 hours after an exogenous GnRH-induced LH surge. Antral GCs (aGCs; aspirated by follicular puncture) and membrane-associated GCs (mGCs; scraped from the follicular wall) were compared with TC expression profiles determined by mRNA microarrays. Of the approximately 11 000 total genes expressed in the periovulatory follicle, only 2% of thecal vs 25% of the granulosa genes changed in response to the LH surge. The majority of the 203 LH-regulated thecal genes were also LH regulated in GCs, leaving a total of 57 genes as LH-regulated TC-specific genes. Of the 57 thecal-specific LH-regulated genes, 74% were down-regulated including CYP17A1 and NR5A1, whereas most other genes are being identified for the first time within theca. Many of the newly identified up-regulated thecal genes (eg, PTX3, RND3, PPP4R4) were also up-regulated in granulosa. Minimal expression differences were observed between aGCs and mGCs; however, transcripts encoding extracellular proteins (NID2) and matrix modulators (ADAMTS1, SASH1) dominated these differences. We also identified large numbers of unknown LH-regulated GC genes and discuss their putative roles in ovarian function. This Research Resource provides an easy-to-access global evaluation of LH regulation in TCs and GCs that implicates numerous molecular pathways heretofore unknown within the follicle.

  7. Effects of cetrorelix, a GnRH-receptor antagonist, on gonadal axis in women with functional hypothalamic amenorrhea.

    PubMed

    Berardelli, Rita; Gianotti, Laura; Karamouzis, Ioannis; Picu, Andreea; Giordano, Roberta; D'Angelo, Valentina; Zinnà, Domenico; Lanfranco, Fabio; Ghigo, Ezio; Arvat, Emanuela

    2011-10-01

    Gonadotropin Releasing Hormone (GnRH) antagonists (GnRHa) suppress gonadotropin and sex-steroid secretion. In normal women, acute GnRHa administration induces inhibitory effect on pituitary-gonadal axis, followed by Luteinizing Hormone (LH) rebound. Functional hypothalamic amenorrhea (HA) is characterised by impaired gonadotropin secretion and hypogonadism secondary to blunted GnRH pulsatility. We studied the effects of a GnRHa, cetrorelix (CTX 3.0 mg), in six women with HA (age 30.7 ± 3.2 years; BMI 21.5 ± 1.7 kg/m(2)) and six control subjects (CS, 28.2 ± 0.6 years; 22.6 ± 0.9 kg/m(2)) on LH, Follicle-Stimulating Hormone (FSH) and oestradiol levels over 4 h (08.00-12.00 am) before, +24 h and +96 h after CTX; LH, FSH, and oestradiol were also evaluated at +6, +8, +12, +48, +72 h after CTX. CS: CTX reduced (p < 0.05) LH, FSH, and oestradiol (nadir at +12 h, +24 h, and +24 h); LH rebounded at +96 h, FSH and oestradiol recovered at +48 h and +72 h. The 4-h evaluation showed LH and FSH reduction (p < 0.05) at +24 h, with LH rebound at +96 h. HA: CTX reduced (p < 0.05) LH, FSH, and oestradiol, (nadir at +24 h, +48 h, and +48 h, recovery at +48 h, +72 h, and +96 h). The 4-h evaluation showed gonadotropin reduction (p < 0.05) 24 h after CTX, without any rebound effect. One single CTX dose still modulates gonadotropin secretion in HA. Its 'paradoxical' stimulatory effect on gonadotropins needs to be verified after prolonged administration.

  8. Recovery of pituitary-gonadal function in male and female rats after prolonged administration of a potent antagonist of luteinizing hormone-releasing hormone (SB-75).

    PubMed

    Bokser, L; Srkalovic, G; Szepeshazi, K; Schally, A V

    1991-08-01

    The reversibility of the antifertility effects induced by long-term administration of the LH-RH antagonistic analog [Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10]-LH-RH (SB-75) was investigated in male and female rats. Male rats were implanted with osmotic minipumps releasing 50 micrograms of SB-75/day for 60 days. The control rats were implanted with minipumps containing only vehicle. The treatment with the antagonist caused a significant decrease in the weights of the testes, seminal vesicles and ventral prostates (p less than 0.01) and reduced serum LH and testosterone levels (p less than 0.01). The histology of the testes from the treated rats showed that spermatogenesis was totally depressed. No mature elongated or round spermatids were found in the seminiferous tubules, spermatocytes being the most advanced germ cell form in 100% of the testicular tubules. These changes indicate that a total spermatogenetic arrest occurred in the treated animals. Ninety days after cessation of treatment with the LH-RH antagonist, there was a complete recovery of the weights of the testes, seminal vesicles and ventral prostates and LH and testosterone returned to control levels. Histological studies revealed a complete recovery of spermatogenesis, with 99.2% of seminiferous tubules containing mature elongated spermatids. Immediately after the discontinuation of treatment with SB-75, a significant down-regulation of the pituitary LH-RH receptors was found, but 90 days later, this phenomenon was completely reversed. Female rats were injected every 3 weeks for 6 weeks with SB-75 microcapsules, at a dose calculated to release 27 micrograms/day of the antagonist. The treatment with SB-75 disrupted the normal estrous cycle. Body weights were not affected, but ovarian and uterine weights were significantly decreased (p less than 0.01 and p less than 0.05, respectively) in the animals treated with the antagonist. Treated rats had significantly lower LH (p less than 0.05) and estradiol (p less than 0.01) levels than controls. The histology of the ovaries from the SB-75-treated group showed that the ratio of small to large maturing follicles increased significantly (p less than 0.01) and corpora lutea were absent. Two months after the cessation of treatment, a complete recovery in the organ weights and in hormonal levels was observed and no histological differences were found between the ovaries in treated and untreated rats. These collective results indicate that the suppression of gonadal function induced by the treatment with LH-RH antagonist SB-75 is completely reversible both in male and female animals.(ABSTRACT TRUNCATED AT 400 WORDS)

  9. Germ-line activation of the luteinizing hormone receptor directly drives spermiogenesis in a nonmammalian vertebrate

    PubMed Central

    Chauvigné, François; Zapater, Cinta; Gasol, Josep M.; Cerdà, Joan

    2014-01-01

    In both mammals and teleosts, the differentiation of postmeiotic spermatids to spermatozoa (spermiogenesis) is thought to be indirectly controlled by the luteinizing hormone (LH) acting through the LH/choriogonadotropin receptor (LHCGR) to stimulate androgen secretion in the interstitial Leydig cells. However, a more direct, nonsteroidal role of LH mediating the spermiogenic pathway remains unclear. Using a flatfish with semicystic spermatogenesis, in which spermatids are released into the seminiferous lobule lumen (SLL), where they develop into spermatozoa without direct contact with the supporting Sertoli cells, we show that haploid spermatids express the homolog of the tetrapod LHCGR (Lhcgrba). Both native Lh and intramuscularly injected His-tagged recombinant Lh (rLh) are immunodetected bound to the Lhcgrba of free spermatids in the SLL, showing that circulating gonadotropin can reach the intratubular compartment. In vitro incubation of flatfish spermatids isolated from the SLL with rLh specifically promotes their differentiation into spermatozoa, whereas recombinant follicle-stimulating hormone and steroid hormones are ineffective. Using a repertoire of molecular markers and inhibitors, we find that the Lh-Lhcgrba induction of spermiogenesis is mediated through a cAMP/PKA signaling pathway that initiates the transcription of genes potentially involved in the function of spermatozoa. We further show that Lhcgrba expression in germ cells also occurs in distantly related fishes, suggesting this feature is likely conserved in teleosts regardless of the type of germ cell development. These data reveal a role of LH in vertebrate germ cells, whereby a Lhcgrba-activated signaling cascade in haploid spermatids directs gene expression and the progression of spermiogenesis. PMID:24474769

  10. Dynamics of exciton relaxation in LH2 antenna probed by multipulse nonlinear spectroscopy.

    PubMed

    Novoderezhkin, Vladimir I; Cohen Stuart, Thomas A; van Grondelle, Rienk

    2011-04-28

    We explain the relaxation dynamics in the LH2-B850 antenna as revealed by multipulse pump-dump-probe spectroscopy (Th. A. Cohen Stuart, M. Vengris, V. I. Novoderezhkin, R. J. Cogdell, C. N. Hunter, R. van Grondelle, submitted). The theory of pump-dump-probe response is evaluated using the doorway-window approach in combination with the modified Redfield theory. We demonstrate that a simultaneous fit of linear spectra, pump-probe, and pump-dump-probe kinetics can be obtained at a quantitative level using the disordered exciton model, which is essentially the same as used to model the spectral fluctuations in single LH2 complexes (Novoderezhkin, V.; Rutkauskas, D.; van Grondelle, R. Biophys. J. 2006, 90, 2890). The present studies suggest that the observed relaxation rates are strongly dependent on the realization of the disorder. A big spread of the rates (exceeding 3 orders of magnitude) is correlated with the disorder-induced changes in delocalization length and overlap of the exciton wave functions. We conclude that the bulk kinetics reflect a superposition of many pathways corresponding to different physical limits of energy transfer, varying from sub-20 fs relaxation between delocalized and highly spatially overlapping exciton states to >20 ps jumps between states localized at the opposite sides of the ring.

  11. Strong Coupling of Localized Surface Plasmons to Excitons in Light-Harvesting Complexes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tsargorodska, Anna; Cartron, Michaël L.; Vasilev, Cvetelin

    Gold nanostructure arrays exhibit surface plasmon resonances that split after attaching light harvesting complexes 1 and 2 (LH1 and LH2) from purple bacteria. The splitting is attributed to strong coupling between the localized surface plasmon resonances and excitons in the light-harvesting complexes. Wild-type and mutant LH1 and LH2 from Rhodobacter sphaeroides containing different carotenoids yield different splitting energies, demonstrating that the coupling mechanism is sensitive to the electronic states in the light harvesting complexes. Plasmon–exciton coupling models reveal different coupling strengths depending on the molecular organization and the protein coverage, consistent with strong coupling. Strong coupling was also observed formore » self-assembling polypeptide maquettes that contain only chlorins. However, it is not observed for monolayers of bacteriochlorophyll, indicating that strong plasmon–exciton coupling is sensitive to the specific presentation of the pigment molecules.« less

  12. Strong Coupling of Localized Surface Plasmons to Excitons in Light-Harvesting Complexes

    DOE PAGES

    Tsargorodska, Anna; Cartron, Michaël L.; Vasilev, Cvetelin; ...

    2016-09-30

    Gold nanostructure arrays exhibit surface plasmon resonances that split after attaching light harvesting complexes 1 and 2 (LH1 and LH2) from purple bacteria. The splitting is attributed to strong coupling between the localized surface plasmon resonances and excitons in the light-harvesting complexes. Wild-type and mutant LH1 and LH2 from Rhodobacter sphaeroides containing different carotenoids yield different splitting energies, demonstrating that the coupling mechanism is sensitive to the electronic states in the light harvesting complexes. Plasmon–exciton coupling models reveal different coupling strengths depending on the molecular organization and the protein coverage, consistent with strong coupling. Strong coupling was also observed formore » self-assembling polypeptide maquettes that contain only chlorins. However, it is not observed for monolayers of bacteriochlorophyll, indicating that strong plasmon–exciton coupling is sensitive to the specific presentation of the pigment molecules.« less

  13. Effects of unilateral laser-assisted ventriculocordectomy in horses with laryngeal hemiplegia.

    PubMed

    Robinson, P; Derksen, F J; Stick, J A; Sullins, K E; DeTolve, P G; Robinson, N E

    2006-11-01

    Recent studies have evaluated surgical techniques aimed at reducing noise and improving airway function in horses with recurrent laryngeal neuropathy (RLN). These techniques require general anaesthesia and are invasive. A minimally invasive transnasal surgical technique for treatment of RLN that may be employed in the standing, sedated horse would be advantageous. To determine whether unilateral laser-assisted ventriculocordectomy (LVC) improves upper airway function and reduces noise during inhalation in exercising horses with laryngeal hemiplegia (LH). Six Standardbred horses were used; respiratory sound and inspiratory transupper airway pressure (Pui) measured before and after induction of LH, and 60, 90 and 120 days after LVC. Inspiratory sound level (SL) and the sound intensities of formants 1, 2 and 3 (Fl, F2 and F3, respectively), were measured using computer-based sound analysis programmes. In addition, upper airway endoscopy was performed at each time interval, at rest and during treadmill exercise. In LH-affected horses, Pui, SL and the sound intensity of F2 and F3 were increased significantly from baseline values. At 60 days after LVC, Pui and SL had returned to baseline, and F2 and F3 values had improved partially compared to LH values. At 90 and 120 days, however, SL increased again to LH levels. LVC decreases LH-associated airway obstruction by 60 days after surgery, and reduces inspiratory noise but not as effectively as bilateral ventriculocordectomy. LVC may be recommended as a treatment of LH, where reduction of upper airway obstruction and respiratory noise is desired and the owner wishes to avoid risks associated with a laryngotomy incision or general anaesthesia.

  14. Direct Observation of Energy Detrapping in LH1-RC Complex by Two-Dimensional Electronic Spectroscopy.

    PubMed

    Ma, Fei; Yu, Long-Jiang; Hendrikx, Ruud; Wang-Otomo, Zheng-Yu; van Grondelle, Rienk

    2017-01-18

    The purple bacterial core light harvesting antenna-reaction center (LH1-RC) complex is the simplest system able to achieve the entire primary function of photosynthesis. During the past decade, a variety of photosynthetic proteins were studied by a powerful technique, two-dimensional electronic spectroscopy (2DES). However, little attention has been paid to LH1-RC, although its reversible uphill energy transfer, trapping, and backward detrapping processes, represent a crucial step in the early photosynthetic reaction dynamics. Thus, in this work, we employed 2DES to study two LH1-RC complexes of Thermochromatium (Tch.) tepidum. By direct observation of detrapping, the complex reversible process was clearly identified and an overall scheme of the excitation evolution in LH1-RC was obtained.

  15. Developmental programming: Prenatal BPA treatment disrupts timing of LH surge and ovarian follicular wave dynamics in adult sheep

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Veiga-Lopez, A.; Beckett, E.M.; Abi Salloum, B.

    Developmental exposure to BPA adversely affects reproductive function. In sheep, prenatal BPA treatment induces reproductive neuroendocrine defects, manifested as LH excess and dampened LH surge and perturbs early ovarian gene expression. In this study we hypothesized that prenatal BPA treatment will also disrupt ovarian follicular dynamics. Pregnant sheep were treated from days 30 to 90 of gestation with 3 different BPA doses (0.05, 0.5, or 5 mg/kg BW/day). All female offspring were estrus synchronized and transrectal ultrasonography was performed daily for 22 days to monitor ovarian follicular and corpora lutea dynamics. Blood samples were collected to assess preovulatory hormonal changesmore » and luteal progesterone dynamics. Statistical analysis revealed that the time interval between the estradiol rise and the preovulatory LH surge was shortened in the BPA-treated females. None of the three BPA doses had an effect on corpora lutea, progestogenic cycles, and mean number or duration of ovulatory and non-ovulatory follicles. However, differences in follicular count trajectories were evident in all three follicular size classes (2–3 mm, 4–5 mm, and ≥ 6 mm) of prenatal BPA-treated animals compared to controls. Number of follicular waves tended also to be more variable in the prenatal BPA-treated groups ranging from 2 to 5 follicular waves per cycle, while this was restricted to 3 to 4 waves in control females. These changes in ovarian follicular dynamics coupled with defects in time interval between estradiol rise and preovulatory LH release are likely to lead to subfertility in prenatal BPA-treated females. - Highlights: • Prenatal BPA shortens interval between estradiol rise and preovulatory LH surge. • Prenatal BPA affects follicular count trajectory and follicular wave occurrence. • Prenatal BPA does not affect ovulatory rate and progesterone dynamics.« less

  16. Interactions between rewarding lateral hypothalamic and aversive nucleus reticularis gigantocellularis stimulation.

    PubMed

    Diotte, M; Miguelez, M; Miliaressis, E; Bielajew, C

    2000-12-05

    The interaction between rewarding and aversive consequences of brain stimulation were assessed in two studies. In the first, the frequency threshold for 300 ms trains of combined lateral hypothalamic (LH) and nucleus reticularis gigantocellularis (Gi) stimulation, in which each LH pulse was followed 2 ms later by the Gi one, was determined for one month. Compared to the threshold for trains of single LH pulses, combined LH-Gi stimulation initially increased the frequency threshold; however, this effect reversed within one session and was subsequently maintained for the duration of the study. The aversion produced by Gi stimulation, as measured by latency to escape, was abolished following a single session of LH-Gi pairs. In the second study, a subset of animals received both presentations of combined pulses, LH followed by Gi, and the reverse; the interval between pulses was varied from 0.2 to 6.4 ms. The effectiveness of combined stimulation, determined by the ratio of LH frequency thresholds to that of the LH-Gi ranged from 0 to 50% across animals but the individual effectiveness functions within animals did not vary with different intervals. In addition, the order of presentation of pulses was of no consequence. Thus, not only did exposure to LH stimulation appear to obliterate Gi aversion, but the combination of LH and Gi pulses added to the rewarding effect produced by LH stimulation alone.

  17. Computational investigation of the effect of pH on the color of firefly bioluminescence by DFT.

    PubMed

    Pinto da Silva, Luís; Esteves da Silva, Joaquim C G

    2011-04-04

    In spite of recent advances towards understanding the mechanism of firefly bioluminescence, there is no consensus about which oxyluciferin (OxyLH(2)) species are the red and yellow-green emitters. The crystal structure of Luciola cruciata luciferase (LcLuc) revealed different conformations for the various steps of the bioluminescence reaction, with different degrees of polarity and rigidity of the active-site microenvironment. In this study, these different conformations of luciferase (Luc) are simulated and their effects on the different chemical equilibria of OxyLH(2) are investigated as a function of pH by means of density functional theory with the PBE0 functional. In particular, the thermodynamic properties and the absorption spectra of each species, as well as their relative stabilities in the ground and excited states, were computed in the different conformations of Luc. From the calculations it is possible to derive the acid dissociation and tautomeric constants, and the corresponding distribution diagrams. It is observed that the anionic keto form of OxyLH(2) is both the red and the yellow-green emitter. Consequently, the effect of Luc conformations on the structural and electronic properties of the Keto-(-1) form are studied. Finally, insights into the Luc-catalyzed light-emitting reaction are derived from the calculations. The multicolor bioluminescence can be explained by interactions of the emitter with active-site molecules, the effects of which on light emission are modulated by the internal dielectric constant of the different conformations. These interactions can suffer also from rearrangement due to entry of external solvent and changes in the protonation state of some amino acid residues and adenosine monophosphate (AMP). Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Solvation effect of bacteriochlorophyll excitons in light-harvesting complex LH2.

    PubMed

    Urboniene, V; Vrublevskaja, O; Trinkunas, G; Gall, A; Robert, B; Valkunas, L

    2007-09-15

    We have characterized the influence of the protein environment on the spectral properties of the bacteriochlorophyll (Bchl) molecules of the peripheral light-harvesting (or LH2) complex from Rhodobacter sphaeroides. The spectral density functions of the pigments responsible for the 800 and 850 nm electronic transitions were determined from the temperature dependence of the Bchl absorption spectra in different environments (detergent micelles and native membranes). The spectral density function is virtually independent of the hydrophobic support that the protein experiences. The reorganization energy for the B850 Bchls is 220 cm(-1), which is almost twice that of the B800 Bchls, and its Huang-Rhys factor reaches 8.4. Around the transition point temperature, and at higher temperatures, both the static spectral inhomogeneity and the resonance interactions become temperature-dependent. The inhomogeneous distribution function of the transitions exhibits less temperature dependence when LH2 is embedded in membranes, suggesting that the lipid phase protects the protein. However, the temperature dependence of the fluorescence spectra of LH2 cannot be fitted using the same parameters determined from the analysis of the absorption spectra. Correct fitting requires the lowest exciton states to be additionally shifted to the red, suggesting the reorganization of the exciton spectrum.

  19. Molecular and behavioral profiling of Dbx1-derived neurons in the arcuate, lateral and ventromedial hypothalamic nuclei.

    PubMed

    Sokolowski, Katie; Tran, Tuyen; Esumi, Shigeyuki; Kamal, Yasmin; Oboti, Livio; Lischinsky, Julieta; Goodrich, Meredith; Lam, Andrew; Carter, Margaret; Nakagawa, Yasushi; Corbin, Joshua G

    2016-05-21

    Neurons in the hypothalamus function to regulate the state of the animal during both learned and innate behaviors, and alterations in hypothalamic development may contribute to pathological conditions such as anxiety, depression or obesity. Despite many studies of hypothalamic development and function, the link between embryonic development and innate behaviors remains unexplored. Here, focusing on the embryonically expressed homeodomain-containing gene Developing Brain Homeobox 1 (Dbx1), we explored the relationship between embryonic lineage, post-natal neuronal identity and lineage-specific responses to innate cues. We found that Dbx1 is widely expressed across multiple developing hypothalamic subdomains. Using standard and inducible fate-mapping to trace the Dbx1-derived neurons, we identified their contribution to specific neuronal subtypes across hypothalamic nuclei and further mapped their activation patterns in response to a series of well-defined innate behaviors. Dbx1-derived neurons occupy multiple postnatal hypothalamic nuclei including the lateral hypothalamus (LH), arcuate nucleus (Arc) and the ventral medial hypothalamus (VMH). Within these nuclei, Dbx1 (+) progenitors generate a large proportion of the Pmch-, Nesfatin-, Cart-, Hcrt-, Agrp- and ERα-expressing neuronal populations, and to a lesser extent the Pomc-, TH- and Aromatase-expressing populations. Inducible fate-mapping reveals distinct temporal windows for development of the Dbx1-derived LH and Arc populations, with Agrp(+) and Cart(+) populations in the Arc arising early (E7.5-E9.5), while Pmch(+) and Hcrt(+) populations in the LH derived from progenitors expressing Dbx1 later (E9.5-E11.5). Moreover, as revealed by c-Fos labeling, Dbx1-derived cells in male and female LH, Arc and VMH are responsive during mating and aggression. In contrast, Dbx1-lineage cells in the Arc and LH have a broader behavioral tuning, which includes responding to fasting and predator odor cues. We define a novel fate map of the hypothalamus with respect to Dbx1 expression in hypothalamic progenitor zones. We demonstrate that in a temporally regulated manner, Dbx1-derived neurons contribute to molecularly distinct neuronal populations in the LH, Arc and VMH that have been implicated in a variety of hypothalamic-driven behaviors. Consistent with this, Dbx1-derived neurons in the LH, Arc and VMH are activated during stress and other innate behavioral responses, implicating their involvement in these diverse behaviors.

  20. Resonance Raman and surface-enhanced resonance Raman spectra of LH2 antenna complex from Rhodobacter sphaeroides and Ectothiorhodospira sp. excited in the Qx and Qy transitions.

    PubMed

    Chumanov, G; Picorel, R; Ortiz de Zarate, I; Cotton, T M; Seibert, M

    2000-05-01

    Well-resolved vibrational spectra of LH2 complex isolated from two photosynthetic bacteria, Rhodobacter sphaeroides and Ectothiorhodospira sp., were obtained using surface-enhanced resonance Raman scattering (SERRS) exciting into the Qx and the Qy transitions of bacteriochlorophyll a. High-quality SERRS spectra in the Qy region were accessible because the strong fluorescence background was quenched near the roughened Ag surface. A comparison of the spectra obtained with 590 nm and 752 nm excitation in the mid- and low-frequency regions revealed spectral differences between the two LH2 complexes as well as between the LH2 complexes and isolated bacteriochlorophyll a. Because peripheral modes of pigments contribute mainly to the low-frequency spectral region, frequencies and intensities of many vibrational bands in this region are affected by interactions with the protein. The results demonstrate that the microenvironment surrounding the pigments within the two LH2 complexes is somewhat different, despite the fact that the complexes exhibit similar electronic absorption spectra. These differences are most probably due to specific pigment-pigment and pigment-protein interactions within the LH2 complexes, and the approach might be useful for addressing subtle static and dynamic structural variances between pigment-protein complexes from different sources or in complexes altered chemically or genetically.

  1. The utility of the gonadotrophin releasing hormone (GnRH) test in the diagnosis of polycystic ovary syndrome (PCOS).

    PubMed

    Lewandowski, Krzysztof C; Cajdler-Łuba, Agata; Salata, Ireneusz; Bieńkiewicz, Małgorzata; Lewiński, Andrzej

    2011-01-01

    Polycystic ovary syndrome (PCOS) is characterised by increased frequency of hypothalamic GnRH pulses leading to a relative increase in LH synthesis by the pituitary. As GnRH stimulation can reveal a relative LH excess, we have endeavoured to assess whether GnRH test might be useful in the diagnosis of PCOS. The study involved 185 subjects: a PCOS group, n = 151, all with oligo- or amenorrhoea, aged (mean ± SD) 24.8 ± ± 5.4 years, BMI 24.5 ± 6.0 kg/m²; and regularly menstruating controls, n = 34, aged 26.6 ± 5.0 years, BMI 24.6 ± 5.5 kg/m². In 121 subjects with PCOS and in 32 controls, serum LH and FSH were measured before (0 minutes) and 30 and 60 minutes after GnRH stimulation (100 μg i.v.). Insulin resistance was assessed by HOMA and Insulin Resistance Index derived from glucose and insulin concentrations during 75 gram oral glucose tolerance test. Women with PCOS had higher testosterone (p = 0.0002), androstendione (p = 0.0021), 17OH-progesterone (p < 0.0001) and were more insulin resistant. Raised concentrations of at least one androgen were, however, found only in 58.1% of women with PCOS. Baseline and stimulated LH concentrations were higher in PCOS (9.09 ± 5.56 vs 4.83 ± 1.71 IU/L, 35.48 ± 31.4 vs 16.30 ± 6.68 IU/L, 33.86 ± 31.8 vs 13.45 ± 5.2 IU/L, at 0, 30 and 60 mins post GnRH, respectively, p < 0.0001). There was no difference in baseline or stimulated FSH concentrations between groups. Relative increases of LH or FSH in comparison to respective baseline values were similar in both groups. There was, however, a marked increase in LH/FSH ratio in PCOS in comparison to controls (LH0 min/FSH(₀ min) 1.59 ± 0.95 vs 0.76 ± 0.2, LH(₃₀ min) /FSH(₃₀ min) 4.07 ± 3.0 vs 1.89 ± 0.79, LH(₆₀ min)/FSH(₆₀ min) 3.56 ± 2.58 vs 1.55 ± 0.63, p < 0.0001 at all time points). Further analysis revealed that LH30 min/FSH(₃₀ min) > 2.11 or LH(₆₀ min)/FSH(₆₀ min) > 1.72 had 78.3% and 87.5% sensitivity and 81.7% and 81.3% specificity for the diagnosis of PCOS, respectively. Women with PCOS have higher baseline and GnRH-stimulated LH concentrations. GnRH stimulation results in an increase in LH/FSH ratio in women with PCOS. Therefore we postulate that this phenomenon might be potentially useful as an additional tool in the diagnosis of PCOS.

  2. Responses to constant infusion of LH-RH in girls with primary hypogonadism.

    PubMed

    Reiter, E O; Duckett, G E; Root, A W

    1980-09-01

    To further assess quantitative pituitary gonadotropin release in patients with primary hypogonadism, a 3-hour constant infusion of the synthetic gonadotropin-releasing hormone, LH-RH, was administered to 12 functionally agonadal girls (11 with Turner syndrome and 1 who had been overiectomized), aged 9.5 to 19.42 years. Gonadotropin and sex steroid responses were determined before and during the infusion and contrasted to those in normal pubertal females. in girls with skeletal age under 11 years, mean control LH increased (P < .001) from 2.2 +/- 0.3 (mean +/- SEM) mIU/ml to 21.3 +/- 7.3 during LH-RH infusion, while luteinizing hormone (LH) rose (P < .001) from 89.2 +/- 24.6 to 276.5 +/- 42.6 girls with skeletal age over 11 years. This age-related augmentation is an exaggeration of data in normal girls and occcurs despite minimal gonadal secretion of sex steroids. A similar age-related discrepancy was not seen in follicle-stimulating hormone (FSH) secretion evoked by LH-RH; all girls had FSH increments into the castrate range with a rise from mean control levels of 78.6 +/- 6.7 to 133.9 +/- 8.3. These data demonstrate an age-related increase in LH-RH-evoked LH secretion, but not of FSH, in children and adolescents with primary hypogonadism.

  3. DynPeak: An Algorithm for Pulse Detection and Frequency Analysis in Hormonal Time Series

    PubMed Central

    Vidal, Alexandre; Zhang, Qinghua; Médigue, Claire; Fabre, Stéphane; Clément, Frédérique

    2012-01-01

    The endocrine control of the reproductive function is often studied from the analysis of luteinizing hormone (LH) pulsatile secretion by the pituitary gland. Whereas measurements in the cavernous sinus cumulate anatomical and technical difficulties, LH levels can be easily assessed from jugular blood. However, plasma levels result from a convolution process due to clearance effects when LH enters the general circulation. Simultaneous measurements comparing LH levels in the cavernous sinus and jugular blood have revealed clear differences in the pulse shape, the amplitude and the baseline. Besides, experimental sampling occurs at a relatively low frequency (typically every 10 min) with respect to LH highest frequency release (one pulse per hour) and the resulting LH measurements are noised by both experimental and assay errors. As a result, the pattern of plasma LH may be not so clearly pulsatile. Yet, reliable information on the InterPulse Intervals (IPI) is a prerequisite to study precisely the steroid feedback exerted on the pituitary level. Hence, there is a real need for robust IPI detection algorithms. In this article, we present an algorithm for the monitoring of LH pulse frequency, basing ourselves both on the available endocrinological knowledge on LH pulse (shape and duration with respect to the frequency regime) and synthetic LH data generated by a simple model. We make use of synthetic data to make clear some basic notions underlying our algorithmic choices. We focus on explaining how the process of sampling affects drastically the original pattern of secretion, and especially the amplitude of the detectable pulses. We then describe the algorithm in details and perform it on different sets of both synthetic and experimental LH time series. We further comment on how to diagnose possible outliers from the series of IPIs which is the main output of the algorithm. PMID:22802933

  4. Neonatal Exposure to Bisphenol A Alters Reproductive Parameters and Gonadotropin Releasing Hormone Signaling in Female Rats

    PubMed Central

    Fernández, Marina; Bianchi, Maria; Lux-Lantos, Victoria; Libertun, Carlos

    2009-01-01

    Background Bisphenol A (BPA) is a component of polycarbonate plastics, epoxy resins, and polystyrene and is found in many products. Several reports have revealed potent in vivo effects, because BPA acts as an estrogen agonist and/or antagonist and as an androgen and thyroid hormone antagonist. Objectives We analyzed the effects of neonatal exposure to BPA on the reproductive axis of female Sprague-Dawley rats. Methods Female rats were injected subcutaneusly, daily, from postnatal day 1 (PND1) to PND10 with BPA [500 μg/50 μL (high) or 50 μg/50 μL (low)] in castor oil or with castor oil vehicle alone. We studied body weight and age at vaginal opening, estrous cycles, and pituitary hormone release in vivo and in vitro, as well as gonadotropin-releasing hormone (GnRH) pulsatility at PND13 and in adults. We also analyzed two GnRH-activated signaling pathways in the adults: inositol-triphosphate (IP3), and extracellular signal-regulated kinase1/2 (ERK1/2). Results Exposure to BPA altered pituitary function in infantile rats, lowering basal and GnRH-induced luteinizing hormone (LH) and increasing GnRH pulsatility. BPA dose-dependently accelerated puberty onset and altered estrous cyclicity, with the high dose causing permanent estrus. In adults treated neonatally with BPA, GnRH-induced LH secretion in vivo was decreased and GnRH pulsatility remained disrupted. In vitro, pituitary cells from animals treated with BPA showed lower basal LH and dose-dependently affected GnRH-induced IP3 formation; the high dose also impaired GnRH-induced LH secretion. Both doses altered ERK1/2 activation. Conclusions Neonatal exposure to BPA altered reproductive parameters and hypothalamic–pituitary function in female rats. To our knowledge, these results demonstrate for the first time that neonatal in vivo BPA permanently affects GnRH pulsatility and pituitary GnRH signaling. PMID:19479018

  5. Quantum coherence spectroscopy reveals complex dynamics in bacterial light-harvesting complex 2 (LH2).

    PubMed

    Harel, Elad; Engel, Gregory S

    2012-01-17

    Light-harvesting antenna complexes transfer energy from sunlight to photosynthetic reaction centers where charge separation drives cellular metabolism. The process through which pigments transfer excitation energy involves a complex choreography of coherent and incoherent processes mediated by the surrounding protein and solvent environment. The recent discovery of coherent dynamics in photosynthetic light-harvesting antennae has motivated many theoretical models exploring effects of interference in energy transfer phenomena. In this work, we provide experimental evidence of long-lived quantum coherence between the spectrally separated B800 and B850 rings of the light-harvesting complex 2 (LH2) of purple bacteria. Spectrally resolved maps of the detuning, dephasing, and the amplitude of electronic coupling between excitons reveal that different relaxation pathways act in concert for optimal transfer efficiency. Furthermore, maps of the phase of the signal suggest that quantum mechanical interference between different energy transfer pathways may be important even at ambient temperature. Such interference at a product state has already been shown to enhance the quantum efficiency of transfer in theoretical models of closed loop systems such as LH2.

  6. Quantum coherence spectroscopy reveals complex dynamics in bacterial light-harvesting complex 2 (LH2)

    PubMed Central

    Harel, Elad; Engel, Gregory S.

    2012-01-01

    Light-harvesting antenna complexes transfer energy from sunlight to photosynthetic reaction centers where charge separation drives cellular metabolism. The process through which pigments transfer excitation energy involves a complex choreography of coherent and incoherent processes mediated by the surrounding protein and solvent environment. The recent discovery of coherent dynamics in photosynthetic light-harvesting antennae has motivated many theoretical models exploring effects of interference in energy transfer phenomena. In this work, we provide experimental evidence of long-lived quantum coherence between the spectrally separated B800 and B850 rings of the light-harvesting complex 2 (LH2) of purple bacteria. Spectrally resolved maps of the detuning, dephasing, and the amplitude of electronic coupling between excitons reveal that different relaxation pathways act in concert for optimal transfer efficiency. Furthermore, maps of the phase of the signal suggest that quantum mechanical interference between different energy transfer pathways may be important even at ambient temperature. Such interference at a product state has already been shown to enhance the quantum efficiency of transfer in theoretical models of closed loop systems such as LH2. PMID:22215585

  7. [Clinical values of single or repeated triptorelin stimulating test in the differential diagnosis between idiopathic hypogonadotropic hypogonadism and constitutional delayed puberty].

    PubMed

    Mao, Jiang-Feng; Wu, Xue-Yan; Lu, Shuang-Yu; Nie, Min

    2011-10-01

    To investigate the values of single or repeated luteinizing hormone (LH) releasing hormone analogue (triptorelin) stimulating test in the differential diagnosis between idiopathic hypogonadotropic hypogonadism (IHH) and constitutional delayed puberty (CDP). Male patients (n = 133) without puberty onset after the age of 14 were recruited for triptorelin stimulating test and were followed up for 24 - 48 months until the diagnosis were confirmed: 86 were IHH and the other 47 were CDP. Repeated triptorelin stimulating tests were conducted in 9 IHH patients and 13 CDP patients one year after the first stimulating tests with an attempt to evaluate the dynamic change of hypothalamus-pituitary-testis axis function. The relationship between the final diagnosis and the peak LH value (LH(max)), and the changes of repeated LH(max) were investigated. In the single triptorelin stimulating test, LH(max) was (1.9 +/- 1.2) U/L in IHH group, which was significantly lower than that in CDP group [(13.7 +/- 8.3) U/L] (P < 0.01); 75 IHH patients (87.2%) had a LH(max) lower than 4 U/L, while only 2 CDP patients (4.3%) had a LH(max) lower than 4 U/L. When LH(max) < 4U/L was used as a criteria for the diagnosis of IHH, the single triptorelin stimulating test had a sensitivity of 87.2%, a specificity of 95.7%, and a positive predictive value of 97.4%. The repeated triptorelin stimulating tests performed one year later showed that the LH(max) in the 9 IHH patients increased from (4.7 +/- 2.5) U/L to (5.1 +/- 3.3) U/L (P = 0.78), while that in the 13 CDP patients increased from (10.7 +/- 3.3) U/L to (24.5 +/- 5.7) U/L (P < 0.05). A single triptorelin stimulating test is highly effective in differentiating IHH from CDP. For some patients without definitive diagnosis, a repeated triptorelin stimulating test performed one year later may provide more valuable information on the dynamic change of the hypothalamus-pituitary-testis axis function.

  8. Preserved visual lexicosemantics in global aphasia: a right-hemisphere contribution?

    PubMed

    Gold, B T; Kertesz, A

    2000-12-01

    Extensive testing of a patient, GP, who encountered large-scale destruction of left-hemisphere (LH) language regions was undertaken in order to address several issues concerning the ability of nonperisylvian areas to extract meaning from printed words. Testing revealed recognition of superordinate boundaries of animals, tools, vegetables, fruit, clothes, and furniture. GP was able to distinguish proper names from other nouns and from nonwords. GP was also able to differentiate words representing living things from those denoting nonliving things. The extent of LH infarct resulting in a global impairment to phonological and syntactic processing suggests LH specificity for these functions but considerable right-hemisphere (RH) participation in visual lexicosemantic processing. The relative preservation of visual lexicosemantic abilities despite severe impairment to all aspects of phonological coding demonstrates the importance of the direct route to the meaning of single printed words.

  9. Differential expression and localization of four connexins in the ovary of the ayu (Plecoglossus Altivelis)

    USGS Publications Warehouse

    Yamamoto, Y.; Yoshizaki, G.; Takeuchi, T.; Soyano, K.; Itoh, F.; Patino, R.

    2007-01-01

    The post-vitellogenic oocytes of teleost fish are generally unresponsive to maturation-inducing hormone (MIH) until a luteinizing hormone (LH) surge stimulates sensitivity via the acquisition of oocyte-maturational competence (OMC). Heterologous gap junctions (GJs) between granulosa cells and the oocyte have been previously implicated in the regulation of oocyte maturation in various vertebrate species. Although heterologous GJ are present in ovarian follicles of ayu (Plecoglossus altivelis), their role in maturation remains unclear. In the present study, we cloned and characterized complementary DNAs for GJ protein connexin (Cx), and examined the expression pattern of Cx messenger RNAs in the ayu ovary. Four Cx cDNAs with predicted molecular masses of 32.1 (Cx32.1), 34.9 (Cx34.9), 44.1 (Cx44.1), and 44.2 (Cx44.2) kDa, respectively, were cloned. Northern blot analysis revealed that the levels of Cx44.1 and Cx44.2 transcripts were similar during the vitellogenic and ovulatory stages. Cx32.1 transcripts were more abundant during the vitellogenic stage, but their levels declined thereafter. Cx34.9 transcript levels increased during the vitellogenic stage and remained high during the acquisition of OMC. In situ hybridization revealed that Cx44.1 and Cx44.2 signals were restricted to the oocyte, whereas the Cx32.1 and Cx34.9 signals were detected in both cellular fractions. Furthermore, a dye-transfer assay revealed the presence of functional GJs between the oocytes and follicle cells. These results suggest that Cx34.9 contributes to the formation of heterologous GJs between oocytes and granulosa cells. Moreover, GJs formed by Cx34.9 may function during the LH-dependent acquisition of OMC and the MIH-dependent resumption of meiosis in ayu. ?? 2007 Wiley-Liss, Inc.

  10. Pentanuclear heterometallic {Mn(III)(2)Ln(3)} (Ln = Gd, Dy, Tb, Ho) assemblies in an open-book type structural topology: appearance of slow relaxation of magnetization in the Dy(III) and Ho(III) analogues.

    PubMed

    Bag, Prasenjit; Chakraborty, Amit; Rogez, Guillaume; Chandrasekhar, Vadapalli

    2014-07-07

    The reaction of Ln(III) nitrate and Mn(ClO4)2·6H2O salts in the presence of a multidentate sterically unencumbered ligand, (E)-2,2'-(2-hydroxy-3-((2-hydroxyphenylimino)methyl)-5-methylbenzylazanediyl)diethanol (LH4) leads to the isolation of four isostructural pentanuclear hetereometallic complexes [Mn(III)2Gd3(LH)4(NO3)(HOCH3)]ClO4·NO3 (1), [Mn(III)2Dy3(LH)4(NO3)(HOCH3)]ClO4·NO3 (2), [Mn(III)2Tb3(LH)4(NO3)(HOCH3)]ClO4·NO3 (3), and [Mn(III)2Ho3(LH)4(NO3)(HOCH3)]ClO4·NO3 (4) with an open-book type structural topology. 1-4 are dicationic and crystallize in the achiral space group, P21/n. A total of four triply deprotonated ligands, [LH](3-), are involved in holding the pentameric metal framework, {Mn(III)2Ln3}. In these complexes both the lanthanide and the manganese(III) ions are doubly bridged, involving phenolate or ethoxide oxygen atoms. The magnetochemical analysis reveals the presence of global antiferromagnetic interactions among the spin centers at low temperatures in all the four compounds. AC susceptibility measurements show the presence of temperature dependent out-of-phase ac signal for compounds 2 and 4 indicating an SMM behavior.

  11. Rhombus-shaped tetranuclear [Ln4] complexes [Ln = Dy(III) and Ho(III)]: synthesis, structure, and SMM behavior.

    PubMed

    Chandrasekhar, Vadapalli; Hossain, Sakiat; Das, Sourav; Biswas, Sourav; Sutter, Jean-Pascal

    2013-06-03

    The reaction of a new hexadentate Schiff base hydrazide ligand (LH3) with rare earth(III) chloride salts in the presence of triethylamine as the base afforded two planar tetranuclear neutral complexes: [{(LH)2Dy4}(μ2-O)4](H2O)8·2CH3OH·8H2O (1) and [{(LH)2Ho4}(μ2-O)4](H2O)8·6CH3OH·4H2O (2). These neutral complexes possess a structure in which all of the lanthanide ions and the donor atoms of the ligand remain in a perfect plane. Each doubly deprotonated ligand holds two Ln(III) ions in its two distinct chelating coordination pockets to form [LH(Ln)2](4+) units. Two such units are connected by four [μ2-O](2-) ligands to form a planar tetranuclear assembly with an Ln(III)4 core that possesses a rhombus-shaped structure. Detailed static and dynamic magnetic analysis of 1 and 2 revealed single-molecule magnet (SMM) behavior for complex 1. A peculiar feature of the χM" versus temperature curve is that two peaks that are frequency-dependent are revealed, indicating the occurrence of two relaxation processes that lead to two energy barriers (16.8 and 54.2 K) and time constants (τ0 = 1.4 × 10(-6) s, τ0 = 7.2 × 10(-7) s). This was related to the presence of two distinct geometrical sites for Dy(III) in complex 1.

  12. Endoscopic features of lymphoid follicles using blue laser imaging (BLI) endoscopy in the colorectum and its association with chronic bowel symptoms

    PubMed Central

    Takahama, Kazuya; Tahara, Sayumi; Yoshida, Dai; Horiguchi, Noriyuki; Kawamura, Tomohiko; Okubo, Masaaki; Nagasaka, Mitsuo; Nakagawa, Yoshihito; Urano, Makoto; Shibata, Tomoyuki; Tuskamoto, Tetsuya; Ieda, Hiro-o; Kuroda, Makoto; Ohmiya, Naoki

    2017-01-01

    Background/Aim In the colorectum, lymphoid follicles hyperplasia (LH) is sometimes observed as small, round, yellowish-white nodules. The novel image-enhanced endoscopy system named blue laser imaging (BLI) provides enhanced the contrast of surface vessels using lasers for light illumination. We investigated the endoscopic features of LH observed by using BLI endoscopy and its association with chronic bowel symptoms. Patients/Methods 300 participants undergoing colonoscopy for various indications were enrolled. Entire colorectum was observed by using BLI-bright mode with non-magnification view. LH was defined as well demarcated white nodules. Elevated LH with erythema was distinguished as LH severe. Results LHs were observed more clearly by using BLI-bright mode compared to conventional white light colonoscopy and were also histologically confirmed as intense infiltration of lymphocytes or plasmacytes. LH was observed in 134 subjects (44.6%) and 67 (22.3%) were LH severe. LH was associated younger age (Odds ratio (OR) = 1.05, 95%Confidence Interval (95%CI) = 1.03–1.07, P<0.0001) and chronic bowel symptoms including constipation, hard stools, diarrhea and loose stools (all LH: OR = 4.03, 95%CI = 2.36–6.89, P<0.0001, LH severe: OR = 5.31, 95%CI = 2.64–10.71, P<0.0001). LH severe was closely associated with both constipation associated symptoms (OR = 3.94, 95%CI = 1.79–8.66, P = 0.0007) and diarrhea associated symptoms (OR = 5.22, 95%CI = 2.09–13.05, P = 0.0004). In particular, LH severe in the ascending colon was strongly associated with bowel symptoms (P<0.0001). Conclusion LH, visualized by using BLI endoscopy was associated with bowel symptom, raising the possibility of pathogenic role of this endoscopic finding in the functional lower gastrointestinal disorders. PMID:28763491

  13. Functional Consequences of Mannose and Asialoglycoprotein Receptor Ablation*

    PubMed Central

    Mi, Yiling; Coonce, Marcy; Fiete, Dorothy; Steirer, Lindsay; Dveksler, Gabriela; Townsend, R. Reid; Baenziger, Jacques U.

    2016-01-01

    The mannose receptor (ManR, Mrc1) and asialoglycoprotein receptor (ASGR, Asgr1 and Asgr2) are highly abundant endocytic receptors expressed by sinusoidal endothelial cells and parenchymal cells in the liver, respectively. We genetically manipulated either receptor individually or in combination, revealing phenotypic changes in female and male mice associated with changes in circulating levels of many glycoproteins. Both receptors rise and fall in response to progesterone during pregnancy. Thirty percent of Asgr2−/− and 65% of Mrc1−/−Asgr2−/− mice are unable to initiate parturition at the end of pregnancy, whereas Mrc1−/− mice initiate normally. Twenty five percent of Mrc1−/−Asgr2−/− male mice develop priapism when mating due to thrombosis of the penile vein, but neither Mrc1−/− nor Asgr2−/− mice do so. The half-life for luteinizing hormone (LH) clearance increases in Mrc1−/− and Mrc1−/−Asgr2−/− mice but not in Asgr2−/− mice; however, LH and testosterone are elevated in all three knockouts. The ManR clears LH thus regulating testosterone production, whereas the ASGR appears to mediate clearance of an unidentified glycoprotein that increases LH levels. More than 40 circulating glycoproteins are elevated >3.0-fold in pregnant Mrc1−/−Asgr2−/− mice. Pregnancy-specific glycoprotein 23, undetectable in WT mice (<50 ng/ml plasma), reaches levels of 1–10 mg/ml in the plasma of Mrc1−/−Asgr2−/− and Asgr2−/− mice, indicating it is cleared by the ASGR. Elevation of multiple coagulation factors in Mrc1−/−Asgr2−/− mice may account for priapism seen in males. These male and female phenotypic changes underscore the key roles of the ManR and ASGR in controlling circulating levels of numerous glycoproteins critical for regulating reproductive hormones and blood coagulation. PMID:27405760

  14. Some Variations on Total Variation-Based Image Smoothing

    DTIC Science & Technology

    2009-03-01

    isotropic BV seminorm. Given N > 1, we let h = 1/N and consider discrete functions fi, i = (i1, i2), 0 ≤ i1, i2 < N. A discrete Lh2 (I) norm of f is defined...p) given in (23), while the second is the Lh2 -projection of p onto the set K. We note at the end of the next section that this iteration is a special...I) ≤ λ(|f̃ n|BVh(I) − 〈∇hfn, pn〉) = (pn)2. So we can ensure that we’ve computed f̃ to within an error of , i.e., ‖f̃ − f̃n‖ Lh2 (I) ≤ , 5 if we

  15. Dorsal hippocampal microinjection of chlorpheniramine reverses the anxiolytic-like effects of l-histidine and impairs emotional memory in mice.

    PubMed

    Canto-de-Souza, L; Garção, D C; Romaguera, F; Mattioli, R

    2015-02-05

    Several findings have pointed to the role of histaminergic neurotransmission in the modulation of anxiety-like behaviors and emotional memory. The elevated plus-maze (EPM) test has been widely used to investigate the process of anxiety and also has been used to investigate the process of learning and memory. Visual cues are relevant to the formation of spatial maps, and as the hippocampus is involved in this task, experiment 1 explored this issue. Experiment 2 investigated the effects of intraperitoneal (i.p.) injections of l-histidine (LH, a precursor of histamine) and of intra-dorsal hippocampus (intra-DH) injections of chlorpheniramine (CPA, an H1 receptor antagonist) on anxiety and emotional memory in mice re-exposed to the EPM. Mice received saline (SAL) or LH i.p. and SAL or CPA (0.016, 0.052, and 0.16 nmol/0.1 μl) intra-DH prior to Trial 1 (T1) and Trial 2 (T2). No significant changes were observed in the number of enclosed-arm entries (EAE) in T1, an EPM index of general exploratory activity. LH had an anxiolytic-like effect that was reversed by intra-DH injections of CPA. T2 versus T1 analysis revealed that only the lower dose of CPA resulted in impaired emotional memory. Combined injections of LH and CPA revealed that higher doses of CPA impair emotional memory. Taken together, these results suggest that LH and H1 receptors present in the dorsal hippocampus are involved in anxiety-related behaviors and emotional memory in mice submitted to EPM. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Molecular Cloning and Characterization of G Alpha Proteins from the Western Tarnished Plant Bug, Lygus hesperus

    PubMed Central

    Hull, J. Joe; Wang, Meixian

    2014-01-01

    The Gα subunits of heterotrimeric G proteins play critical roles in the activation of diverse signal transduction cascades. However, the role of these genes in chemosensation remains to be fully elucidated. To initiate a comprehensive survey of signal transduction genes, we used homology-based cloning methods and transcriptome data mining to identity Gα subunits in the western tarnished plant bug (Lygus hesperus Knight). Among the nine sequences identified were single variants of the Gαi, Gαo, Gαs, and Gα12 subfamilies and five alternative splice variants of the Gαq subfamily. Sequence alignment and phylogenetic analyses of the putative L. hesperus Gα subunits support initial classifications and are consistent with established evolutionary relationships. End-point PCR-based profiling of the transcripts indicated head specific expression for LhGαq4, and largely ubiquitous expression, albeit at varying levels, for the other LhGα transcripts. All subfamilies were amplified from L. hesperus chemosensory tissues, suggesting potential roles in olfaction and/or gustation. Immunohistochemical staining of cultured insect cells transiently expressing recombinant His-tagged LhGαi, LhGαs, and LhGαq1 revealed plasma membrane targeting, suggesting the respective sequences encode functional G protein subunits. PMID:26463065

  17. Identification of protein W, the elusive sixth subunit of the Rhodopseudomonas palustris reaction center-light harvesting 1 core complex.

    PubMed

    Jackson, Philip J; Hitchcock, Andrew; Swainsbury, David J K; Qian, Pu; Martin, Elizabeth C; Farmer, David A; Dickman, Mark J; Canniffe, Daniel P; Hunter, C Neil

    2018-02-01

    The X-ray crystal structure of the Rhodopseudomonas (Rps.) palustris reaction center-light harvesting 1 (RC-LH1) core complex revealed the presence of a sixth protein component, variably referred to in the literature as helix W, subunit W or protein W. The position of this protein prevents closure of the LH1 ring, possibly to allow diffusion of ubiquinone/ubiquinol between the RC and the cytochrome bc 1 complex in analogous fashion to the well-studied PufX protein from Rhodobacter sphaeroides. The identity and function of helix W have remained unknown for over 13years; here we use a combination of biochemistry, mass spectrometry, molecular genetics and electron microscopy to identify this protein as RPA4402 in Rps. palustris CGA009. Protein W shares key conserved sequence features with PufX homologs, and although a deletion mutant was able to grow under photosynthetic conditions with no discernible phenotype, we show that a tagged version of protein W pulls down the RC-LH1 complex. Protein W is not encoded in the photosynthesis gene cluster and our data indicate that only approximately 10% of wild-type Rps. palustris core complexes contain this non-essential subunit; functional and evolutionary consequences of this observation are discussed. The ability to purify uniform RC-LH1 and RC-LH1-protein W preparations will also be beneficial for future structural studies of these bacterial core complexes. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Human Chorionic Gonadotropin: The Pregnancy Hormone and More.

    PubMed

    Theofanakis, Charalampos; Drakakis, Petros; Besharat, Alexandros; Loutradis, Dimitrios

    2017-05-14

    To thoroughly review the uses of human chorionic gonadotropin (hCG) related to the process of reproduction and also assess new, non-traditional theories. Review of the international literature and research studies. hCG and its receptor, LH/CGR, are expressed in numerous sites of the reproductive tract, both in gonadal and extra-goanadal tissues, promoting oocyte maturation, fertilization, implantation and early embryo development. Moreover, hCG seems to have a potential role as an anti-rejection agent in solid organ transplantation. Future research needs to focus extensively on the functions of hCG and its receptor LH/CGR, in an effort to reveal known, as well as unknown clinical potentials.

  19. Learned helplessness predicts functional disability, pain and fatigue in patients with recent-onset inflammatory polyarthritis

    PubMed Central

    Camacho, Elizabeth M.; Verstappen, Suzanne M. M.; Chipping, Jacqueline

    2013-01-01

    Objectives. Cross-sectional studies have found that learned helplessness (LH) is associated with disease outcome in patients with RA. However, little is known about the longitudinal impact of LH. The aim of this study was to investigate whether LH is associated with future disease outcome (disability, pain and fatigue) and to investigate whether LH changes over time in patients with recent-onset inflammatory polyarthritis (IP), the broader group of conditions of which RA is the major constituent. Methods. Patients included in this investigation had been recruited to the Norfolk Arthritis Register, a primary-care-based inception cohort. LH was measured at baseline as patients’ total score on the Rheumatology Attitudes Index (RAI). A total of 443 patients completed the HAQ and visual analogue scales of pain and fatigue at baseline and after 2 years of follow-up. Results. Greater feelings of LH at baseline were associated with higher HAQ scores at follow-up [difference in HAQ score per 1-point increase in RAI score (β-coefficient) 0.02; 95% CI 0.01, 0.04]. Greater baseline LH was also associated with more pain (β-coefficient 1.0; 95% CI 0.4, 1.5) and more fatigue (β-coefficient 1.0; 95% CI 0.2, 1.4) at follow-up. LH was highly changeable during follow-up, with 87% of patients showing any change and 50% improving. Conclusion. Baseline LH independently predicted disability, pain and fatigue at follow-up. Half of patients reported fewer feelings of helplessness after 2 years of follow-up, suggesting that LH may potentially be a modifiable risk factor for disease outcome in IP and a target for intervention. PMID:23424265

  20. Learned helplessness predicts functional disability, pain and fatigue in patients with recent-onset inflammatory polyarthritis.

    PubMed

    Camacho, Elizabeth M; Verstappen, Suzanne M M; Chipping, Jacqueline; Symmons, Deborah P M

    2013-07-01

    Cross-sectional studies have found that learned helplessness (LH) is associated with disease outcome in patients with RA. However, little is known about the longitudinal impact of LH. The aim of this study was to investigate whether LH is associated with future disease outcome (disability, pain and fatigue) and to investigate whether LH changes over time in patients with recent-onset inflammatory polyarthritis (IP), the broader group of conditions of which RA is the major constituent. Patients included in this investigation had been recruited to the Norfolk Arthritis Register, a primary-care-based inception cohort. LH was measured at baseline as patients' total score on the Rheumatology Attitudes Index (RAI). A total of 443 patients completed the HAQ and visual analogue scales of pain and fatigue at baseline and after 2 years of follow-up. Greater feelings of LH at baseline were associated with higher HAQ scores at follow-up [difference in HAQ score per 1-point increase in RAI score (β-coefficient) 0.02; 95% CI 0.01, 0.04]. Greater baseline LH was also associated with more pain (β-coefficient 1.0; 95% CI 0.4, 1.5) and more fatigue (β-coefficient 1.0; 95% CI 0.2, 1.4) at follow-up. LH was highly changeable during follow-up, with 87% of patients showing any change and 50% improving. Baseline LH independently predicted disability, pain and fatigue at follow-up. Half of patients reported fewer feelings of helplessness after 2 years of follow-up, suggesting that LH may potentially be a modifiable risk factor for disease outcome in IP and a target for intervention.

  1. Directed formation of micro- and nanoscale patterns of functional light-harvesting LH2 complexes.

    PubMed

    Reynolds, Nicholas P; Janusz, Stefan; Escalante-Marun, Maryana; Timney, John; Ducker, Robert E; Olsen, John D; Otto, Cees; Subramaniam, Vinod; Leggett, Graham J; Hunter, C Neil

    2007-11-28

    The precision placement of the desired protein components on a suitable substrate is an essential prelude to any hybrid "biochip" device, but a second and equally important condition must also be met: the retention of full biological activity. Here we demonstrate the selective binding of an optically active membrane protein, the light-harvesting LH2 complex from Rhodobacter sphaeroides, to patterned self-assembled monolayers at the micron scale and the fabrication of nanometer-scale patterns of these molecules using near-field photolithographic methods. In contrast to plasma proteins, which are reversibly adsorbed on many surfaces, the LH2 complex is readily patterned simply by spatial control of surface polarity. Near-field photolithography has yielded rows of light-harvesting complexes only 98 nm wide. Retention of the native optical properties of patterned LH2 molecules was demonstrated using in situ fluorescence emission spectroscopy.

  2. Turbopumps for cryogenic upper stage engines. [fabrication and evaluation of turbine pumps for liquid hydrogen and liquid oxygen

    NASA Technical Reports Server (NTRS)

    Zachary, A. T.; Csomor, A.; Tignac, L. L.

    1973-01-01

    Small, high-performance LO2 and LH2 turbopump assembly configurations were selected, detail designs were prepared and two of each unit were fabricated with each unit consisting of pump, turbine gas generator, and appropriate controls. Following fabrication, development testing was conducted on each type to demonstrate performance, durability, transient characteristics, and heat transfer under simulated altitude conditions. Following successful completion of development effort, the two LO2 turbopump units and one LH2 turbopump unit were acceptance tested as specified. Inspection of the units following development testing revealed no deleterious effects of testing. The test results of LO2 turbopump assembly testing correlated well with predicted performance while the LH2 turbopump test results, though generally consistent with predicted values, did show lower than anticipated developed head at the design point and in the high flow range of operation.

  3. Bacterial Phenotype Variants in Group B Streptococcal Toxic Shock Syndrome1

    PubMed Central

    Johansson, Linda; Dahesh, Samira; Van Sorge, Nina M.; Darenberg, Jessica; Norgren, Mari; Sjölin, Jan; Nizet, Victor; Norrby-Teglund, Anna

    2009-01-01

    We conducted genetic and functional analyses of isolates from a patient with group B streptococcal (GBS) necrotizing fasciitis and toxic shock syndrome. Tissue cultures simultaneously showed colonies with high hemolysis (HH) and low hemolysis (LH). Conversely, the HH and LH variants exhibited low capsule (LC) and high capsule (HC) expression, respectively. Molecular analysis demonstrated that the 2 GBS variants were of the same clonal origin. Genetic analysis found a 3-bp deletion in the covR gene of the HH/LC variant. Functionally, this isolate was associated with an increased growth rate in vitro and with higher interleukin-8 induction. However, in whole blood, opsonophagocytic and intracellular killing assays, the LH/HC phenotype demonstrated higher resistance to host phagocytic killing. In a murine model, LH/HC resulted in higher levels of bacteremia and increased host mortality rate. These findings demonstrate differences in GBS isolates of the same clonal origin but varying phenotypes. PMID:19193266

  4. Bacterial phenotype variants in group B streptococcal toxic shock syndrome.

    PubMed

    Sendi, Parham; Johansson, Linda; Dahesh, Samira; Van-Sorge, Nina M; Darenberg, Jessica; Norgren, Mari; Sjölin, Jan; Nizet, Victor; Norrby-Teglund, Anna

    2009-02-01

    We conducted genetic and functional analyses of isolates from a patient with group B streptococcal (GBS) necrotizing fasciitis and toxic shock syndrome. Tissue cultures simultaneously showed colonies with high hemolysis (HH) and low hemolysis (LH). Conversely, the HH and LH variants exhibited low capsule (LC) and high capsule (HC) expression, respectively. Molecular analysis demonstrated that the 2 GBS variants were of the same clonal origin. Genetic analysis found a 3-bp deletion in the covR gene of the HH/LC variant. Functionally, this isolate was associated with an increased growth rate in vitro and with higher interleukin-8 induction. However, in whole blood, opsonophagocytic and intracellular killing assays, the LH/HC phenotype demonstrated higher resistance to host phagocytic killing. In a murine model, LH/HC resulted in higher levels of bacteremia and increased host mortality rate. These findings demonstrate differences in GBS isolates of the same clonal origin but varying phenotypes.

  5. Vanadium(V) Complexes with Substituted 1,5-bis(2-hydroxybenzaldehyde)carbohydrazones and Their Use As Catalyst Precursors in Oxidation of Cyclohexane.

    PubMed

    Dragancea, Diana; Talmaci, Natalia; Shova, Sergiu; Novitchi, Ghenadie; Darvasiová, Denisa; Rapta, Peter; Breza, Martin; Galanski, Markus; Kožı́šek, Jozef; Martins, Nuno M R; Martins, Luísa M D R S; Pombeiro, Armando J L; Arion, Vladimir B

    2016-09-19

    Six dinuclear vanadium(V) complexes have been synthesized: NH4[(VO2)2((H)LH)] (NH4[1]), NH4[(VO2)2((t-Bu)LH)] (NH4[2]), NH4[(VO2)2((Cl)LH)] (NH4[3]), [(VO2)(VO)((H)LH)(CH3O)] (4), [(VO2)(VO)((t-Bu)LH)(C2H5O)] (5), and [(VO2)(VO)((Cl)LH)(CH3O)(CH3OH/H2O)] (6) (where (H)LH4 = 1,5-bis(2-hydroxybenzaldehyde)carbohydrazone, (t-Bu)LH4 = 1,5-bis(3,5-di-tert-butyl-2-hydroxybenzaldehyde)carbohydrazone, and (Cl)LH4 = 1,5-bis(3,5-dichloro-2-hydroxybenzaldehyde)carbohydrazone). The structures of NH4[1] and 4-6 have been determined by X-ray diffraction (XRD) analysis. In all complexes, the triply deprotonated ligand accommodates two V ions, using two different binding sites ONN and ONO separated by a diazine unit -N-N-. In two pockets of NH4[1], two identical VO2(+) entities are present, whereas, in those of 4-6, two different VO2(+) and VO(3+) are bound. The highest oxidation state of V ions was corroborated by X-ray data, indicating the presence of alkoxido ligand bound to VO(3+) in 4-6, charge density measurements on 4, magnetic susceptibility, NMR spectroscopy, spectroelectrochemistry, and density functional theory (DFT) calculations. All four complexes characterized by XRD form dimeric associates in the solid state, which, however, do not remain intact in solution. Compounds NH4[1], NH4[2], and 4-6 were applied as alternative selective homogeneous catalysts for the industrially significant oxidation of cyclohexane to cyclohexanol and cyclohexanone. The peroxidative (with tert-butyl hydroperoxide, TBHP) oxidation of cyclohexane was performed under solvent-free and additive-free conditions and under low-power microwave (MW) irradiation. Cyclohexanol and cyclohexanone were the only products obtained (high selectivity), after 1.5 h of MW irradiation. Theoretical calculations suggest a key mechanistic role played by the carbohydrazone ligand, which can undergo reduction, instead of the metal itself, to form an active reduced form of the catalyst.

  6. Evidence That Dopamine Acts via Kisspeptin to Hold GnRH Pulse Frequency in Check in Anestrous Ewes

    PubMed Central

    Maltby, Matthew J.; Millar, Robert P.; Hileman, Stanley M.; Nestor, Casey C; Whited, Brant; Tseng, Ashlie S.; Coolen, Lique M.; Lehman, Michael N.

    2012-01-01

    Recent work has implicated stimulatory kisspeptin neurons in the arcuate nucleus (ARC) as important for seasonal changes in reproductive function in sheep, but earlier studies support a role for inhibitory A15 dopaminergic (DA) neurons in the suppression of GnRH (and LH) pulse frequency in the nonbreeding (anestrous) season. Because A15 neurons project to the ARC, we performed three experiments to test the hypothesis that A15 neurons act via ARC kisspeptin neurons to inhibit LH in anestrus: 1) we used dual immunocytochemistry to determine whether these ARC neurons contain D2 dopamine receptor (D2-R), the receptor responsible for inhibition of LH in anestrus; 2) we tested the ability of local administration of sulpiride, a D2-R antagonist, into the ARC to increase LH secretion in anestrus; and 3) we determined whether an antagonist to the kisspeptin receptor could block the increase in LH secretion induced by sulpiride in anestrus. In experiment 1, 40% of this ARC neuronal subpopulation contained D2-R in breeding season ewes, but this increased to approximately 80% in anestrus. In experiment 2, local microinjection of the two highest doses (10 and 50 nmol) of sulpiride into the ARC significantly increased LH pulse frequency to levels 3 times that seen with vehicle injections. Finally, intracerebroventricular infusion of a kisspeptin receptor antagonist completely blocked the increase in LH pulse frequency induced by systemic administration of sulpiride to anestrous ewes. These results support the hypothesis that DA acts to inhibit GnRH (and LH) secretion in anestrus by suppressing the activity of ARC kisspeptin neurons. PMID:23038740

  7. Receptor-targeted therapy of human experimental urinary bladder cancers with cytotoxic LH-RH analog AN-152 [AEZS- 108].

    PubMed

    Szepeshazi, Karoly; Schally, Andrew V; Keller, Gunhild; Block, Norman L; Benten, Daniel; Halmos, Gabor; Szalontay, Luca; Vidaurre, Irving; Jaszberenyi, Miklos; Rick, Ferenc G

    2012-07-01

    Many bladder cancers progress to invasion with poor prognosis; new therapeutic methods are needed. We developed a cytotoxic LH-RH analog, AN-152 (AEZS-108) containing doxorubicin (DOX), for targeted therapy of cancers expressing LHRH receptors. We investigated the expression of LH-RH receptors in clinical bladder cancers and in HT-1376, J82, RT-4 and HT-1197 human bladder cancer lines. The effect of analog, AN-152, on growth of these tumor lines xenografted into nude mice was analyzed. Using molecular and functional assays, we also evaluated the differences between the effects of AN-152, and DOX alone. We demonstrated the expression of LH-RH receptors on 18 clinical bladder cancers by immunohistochemistry and on four human urinary bladder cancer lines HT-1376, J82, RT-4 and HT-1197 by Western blotting and binding assays. AN-152 powerfully inhibited growth of these bladder cancers in nude mice. AN-152 exerted greater effects than DOX and was less toxic. DOX activated strong multidrug resistance mechanisms in RT-4 and HT-1197 cancers, while AN-152 had no or less such effect. PCR assays and in vitro studies revealed differences in the action of AN-152 and DOX on the expression of genes involved in apoptosis. These results suggest that targeted cytotoxic LH-RH analog, AN-152 (AEZS- 108), should be examined for treatment of patients with LH-RH receptor positive invasive bladder cancers.

  8. Controlled Ovarian Hyperstimulation with Intrauterine Insemination Is More Successful After r-hCG Administration Than Spontaneous LH Surge.

    PubMed

    Taerk, Evan; Hughes, Edward; Greenberg, Cassandra; Neal, Michael; Amin, Shilpa; Faghih, Mehrnoosh; Karnis, Megan

    2017-01-01

    The purpose of this study was to evaluate whether clinical pregnancy rate is affected by timing intrauterine insemination (IUI) according to serum LH surge, r-hCG trigger, or a combination of LH surge and r-hCG trigger in controlled ovarian hyperstimulation (COH) cycles for patients with a variety of infertility etiologies. The last 365 consecutive COH-IUI cycles performed at ONE Fertility Burlington in 2014 were reviewed and categorized according to method of IUI timing. Associations between categorical variables were analyzed using a combination of Chi-square and Fisher's Exact tests, and between continuous variables using independent sample t-tests and logistic regression to a level of significance of p<0.05. The overall clinical pregnancy rate in this sample was 18.1% (66/365). Administration of r-hCG prior to IUI resulted in a higher clinical pregnancy rate compared with spontaneous serum LH surge: 18.2% vs . 5.8%, p=0.012. Patients in whom r-hCG was administered concomitantly with a serum LH surge had a higher clinical pregnancy than the r-hCG trigger group (30.8% vs . 18.2%, p=0.004) and LH surge group (30.8% vs . 5.8%, p<0.001). A sub-group analysis revealed that patients receiving r-FSH, rather than clomiphene or letrozole, had a significantly higher clinical pregnancy rate after r-hCG trigger as compared to the LH surge group (21.7% vs . 2.1%, p=0.01). In subfertile couples undergoing COH-IUI, r-hCG administration was associated with an increased clinical pregnancy rate compared with spontaneous serum LH surge. When r-hCG was administered concomitantly with a serum LH surge, this benefit was amplified. The effect appears to be of particular importance in r-FSH-medicated cycles.

  9. Fluorescence polarization measures energy funneling in single light-harvesting antennas—LH2 vs conjugated polymers

    NASA Astrophysics Data System (ADS)

    Camacho, Rafael; Tubasum, Sumera; Southall, June; Cogdell, Richard J.; Sforazzini, Giuseppe; Anderson, Harry L.; Pullerits, Tõnu; Scheblykin, Ivan G.

    2015-10-01

    Numerous approaches have been proposed to mimic natural photosynthesis using artificial antenna systems, such as conjugated polymers (CPs), dendrimers, and J-aggregates. As a result, there is a need to characterize and compare the excitation energy transfer (EET) properties of various natural and artificial antennas. Here we experimentally show that EET in single antennas can be characterized by 2D polarization imaging using the single funnel approximation. This methodology addresses the ability of an individual antenna to transfer its absorbed energy towards a single pool of emissive states, using a single parameter called energy funneling efficiency (ɛ). We studied individual peripheral antennas of purple bacteria (LH2) and single CP chains of 20 nm length. As expected from a perfect antenna, LH2s showed funneling efficiencies close to unity. In contrast, CPs showed lower average funneling efficiencies, greatly varying from molecule to molecule. Cyclodextrin insulation of the conjugated backbone improves EET, increasing the fraction of CPs possessing ɛ = 1. Comparison between LH2s and CPs shows the importance of the protection systems and the protein scaffold of LH2, which keep the chromophores in functional form and at such geometrical arrangement that ensures excellent EET.

  10. Fluorescence polarization measures energy funneling in single light-harvesting antennas--LH2 vs conjugated polymers.

    PubMed

    Camacho, Rafael; Tubasum, Sumera; Southall, June; Cogdell, Richard J; Sforazzini, Giuseppe; Anderson, Harry L; Pullerits, Tõnu; Scheblykin, Ivan G

    2015-10-19

    Numerous approaches have been proposed to mimic natural photosynthesis using artificial antenna systems, such as conjugated polymers (CPs), dendrimers, and J-aggregates. As a result, there is a need to characterize and compare the excitation energy transfer (EET) properties of various natural and artificial antennas. Here we experimentally show that EET in single antennas can be characterized by 2D polarization imaging using the single funnel approximation. This methodology addresses the ability of an individual antenna to transfer its absorbed energy towards a single pool of emissive states, using a single parameter called energy funneling efficiency (ε). We studied individual peripheral antennas of purple bacteria (LH2) and single CP chains of 20 nm length. As expected from a perfect antenna, LH2s showed funneling efficiencies close to unity. In contrast, CPs showed lower average funneling efficiencies, greatly varying from molecule to molecule. Cyclodextrin insulation of the conjugated backbone improves EET, increasing the fraction of CPs possessing ε = 1. Comparison between LH2s and CPs shows the importance of the protection systems and the protein scaffold of LH2, which keep the chromophores in functional form and at such geometrical arrangement that ensures excellent EET.

  11. LH pulses and the corpus luteum: the luteal phase deficiency LPD).

    PubMed

    Wuttke, W; Pitzel, L; Seidlová-Wuttke, D; Hinney, B

    2001-01-01

    The proper function of the GnRH pulse generator in the hypothalamus is essential for normal ovarian function, hence also for proper function of the corpus luteum. During the luteal phase LH pulses stimulate progesterone release, which is essential for normal endometrial transformation. Approximately one-half of all luteal phase deficiencies (LPD) are due to improper function of the GnRH pulse generator. Obviously, following ovulation the increased serum progesterone levels oversuppress the GnRH pulse generator, resulting in too few LH pulses and therefore improper luteal function. Also, latent hyperprolactinemia may lead to an LPD which can be effectively treated with plant extracts containing dopaminergic (prolactin-suppressing) compounds. Our increasing knowledge of auto- and paracrine mechanisms between nonsteroidogenic and steroidogenic cells now allow subclassification of LPDs of ovarian origin. The so-called small luteal cells are LH-responsive. If they develop improperly the regularly occurring LH pulses are unable to stimulate progesterone secretion from the small luteal cells, which results in what we call the small luteal cell defect. In addition, there is also evidence that the large luteal cells may function improperly. Hence, basal progesterone release is too low while LH-stimulated progesterone release from the small luteal cells appears to be intact. This subclassification of luteal phase deficiency results in the suggestion of different treatments. In cases where the corpus luteum is LH-responsive, such as the hypothalamic corpus luteum insufficiency and the large luteal cell defect, HCG treatment or pulsatile treatment with GnRH is advisable. In the case of LH/hCG-unresponsive small luteal cell defect a progesterone substitution is suggested.

  12. Developmental Responses of the Lateral Hypothalamus to Leptin in Neonatal Rats, and its Implications for the Development of Functional Connections with the Ventral Tegmental Area.

    PubMed

    Gjerde, E; Long, H; Richard, D; Walker, C-D

    2016-03-01

    Food intake is regulated by a close communication between the hypothalamus and the mesocorticolimbic pathways, which are still developing during the perinatal period in the rat, and are known targets for peripheral metabolic hormones such as leptin. A key region for this communication is the lateral hypothalamus (LH), although the onset of leptin responsiveness in the LH is unknown. We examined the activation of cellular signalling molecules in identified LH neurones on postnatal day (PND)10 and 16 and determined whether leptin directly targets orexin A (ORX-A) or neurotensin (NT) LH neurones through the detection of leptin receptors (ObRb) mRNA on these neurones. Next, using retrograde labelling in PND6 pups, we tested whether phenotypically identified neurones of the LH that respond to leptin project to ventral tegmental area (VTA) neurones. Leptin significantly induced phosphorylated extracellular signal-regulated kinase (pERK)1/2 and phosphorylated signal transducer activator of transcription (pSTAT)3 in the LH on PND16, whereas, on PND10, modest pERK1/2- and sparse pSTAT3-positive cells were identified. On PND16, most pERK1/2-activated neurones contain ORX-A and leptin-induced pSTAT3 was observed in other unidentified neurones. Afferents to the VTA were observed on PND6, including a large input from the LH, which contained both ORX-A-positive and non-ORX-A neurones, with some of these ORX-A neurones being activated by leptin treatment. Leptin receptor (ObRb) mRNA in the LH did not colocalise with ORX-A neurones on PND10, and only a few NT-positive neurones displayed ObRb mRNA expression. Thus, functional responsiveness to leptin in LH neurones is only partially achieved prior to the onset of independent feeding on PND16, and ORX-A neurones are indirectly activated by leptin. The presence of anatomical connections between the LH and the VTA in the first week of life, prior to the development of leptin responsiveness in both structures, suggests that tissue responsiveness to leptin, rather than the maturation of neuronal connections, critically regulates the onset of independent feeding. © 2015 British Society for Neuroendocrinology.

  13. Dependence of the Linker Histone and Chromatin Condensation on the Nucleosome Environment.

    PubMed

    Perišić, Ognjen; Schlick, Tamar

    2017-08-24

    The linker histone (LH), an auxiliary protein that can bind to chromatin and interact with the linker DNA to form stem motifs, is a key element of chromatin compaction. By affecting the chromatin condensation level, it also plays an active role in gene expression. However, the presence and variable concentration of LH in chromatin fibers with different DNA linker lengths indicate that its folding and condensation are highly adaptable and dependent on the immediate nucleosome environment. Recent experimental studies revealed that the behavior of LH in mononucleosomes markedly differs from that in small nucleosome arrays, but the associated mechanism is unknown. Here we report a structural analysis of the behavior of LH in mononucleosomes and oligonucleosomes (2-6 nucleosomes) using mesoscale chromatin simulations. We show that the adapted stem configuration heavily depends on the strength of electrostatic interactions between LH and its parental DNA linkers, and that those interactions tend to be asymmetric in small oligonucleosome systems. Namely, LH in oligonucleosomes dominantly interacts with one DNA linker only, as opposed to mononucleosomes where LH has similar interactions with both linkers and forms a highly stable nucleosome stem. Although we show that the LH condensation depends sensitively on the electrostatic interactions with entering and exiting DNA linkers, other interactions, especially by nonparental cores and nonparental linkers, modulate the structural condensation by softening LH and thus making oligonucleosomes more flexible, in comparison to to mono- and dinucleosomes. We also find that the overall LH/chromatin interactions sensitively depend on the linker length because the linker length determines the maximal nucleosome stem length. For mononucleosomes with DNA linkers shorter than LH, LH condenses fully, while for DNA linkers comparable or longer than LH, the LH extension in mononucleosomes strongly follows the length of DNA linkers, unhampered by neighboring linker histones. Thus, LH is more condensed for mononucleosomes with short linkers, compared to oligonucleosomes, and its orientation is variable and highly environment-dependent. More generally, the work underscores the agility of LH whose folding dynamics critically controls genomic packaging and gene expression.

  14. Excitonic energy transfer in light-harvesting complexes in purple bacteria

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ye Jun; Sun Kewei; Zhao Yang

    Two distinct approaches, the Frenkel-Dirac time-dependent variation and the Haken-Strobl model, are adopted to study energy transfer dynamics in single-ring and double-ring light-harvesting (LH) systems in purple bacteria. It is found that the inclusion of long-range dipolar interactions in the two methods results in significant increase in intra- or inter-ring exciton transfer efficiency. The dependence of exciton transfer efficiency on trapping positions on single rings of LH2 (B850) and LH1 is similar to that in toy models with nearest-neighbor coupling only. However, owing to the symmetry breaking caused by the dimerization of BChls and dipolar couplings, such dependence has beenmore » largely suppressed. In the studies of coupled-ring systems, both methods reveal an interesting role of dipolar interactions in increasing energy transfer efficiency by introducing multiple intra/inter-ring transfer paths. Importantly, the time scale (4 ps) of inter-ring exciton transfer obtained from polaron dynamics is in good agreement with previous studies. In a double-ring LH2 system, non-nearest neighbor interactions can induce symmetry breaking, which leads to global and local minima of the average trapping time in the presence of a non-zero dephasing rate, suggesting that environment dephasing helps preserve quantum coherent energy transfer when the perfect circular symmetry in the hypothetic system is broken. This study reveals that dipolar coupling between chromophores may play an important role in the high energy transfer efficiency in the LH systems of purple bacteria and many other natural photosynthetic systems.« less

  15. Shuttle Main Propulsion System LH2 Feed Line and Inducer Simulations

    NASA Technical Reports Server (NTRS)

    Dorney, Daniel J.; Rothermel, Jeffry

    2002-01-01

    This viewgraph presentation includes simulations of the unsteady flow field in the LH2 feed line, flow line, flow liner, backing cavity and inducer of Shuttle engine #1. It also evaluates aerodynamic forcing functions which may contribute to the formation of the cracks observed on the flow liner slots. The presentation lists the numerical methods used, and profiles a benchmark test case.

  16. Acetyl-L-carnitine (ALC) administration positively affects reproductive axis in hypogonadotropic women with functional hypothalamic amenorrhea.

    PubMed

    Genazzani, A D; Lanzoni, C; Ricchieri, F; Santagni, S; Rattighieri, E; Chierchia, E; Monteleone, P; Jasonni, V M

    2011-04-01

    Hypothalamic amenorrhea (HA) is characterized by neuroendocrine impairment that, in turn, negatively modulates endocrine function, mainly within the reproductive axis. HA presents with hypo-LH, hypoestrogenism and, until now, a definite therapeutic strategy has not yet been found. The aim of the following study was to test the efficacy of acetyl-L-carnitine (ALC) administration in HA-affected subjects. Twenty-four patients affected by stress-induced HA were divided into two groups according to LH plasma levels: group A, hypo-LH (LH≤3 mIU/ml; no.=16), and group B, normo-LH (LH>3 mIU/ml; no.=8), were treated with ALC (1 g/day, per os) for 16 weeks. Patients underwent baseline hormonal assessment, pulsatility test (for LH and FSH), naloxone test (for LH, FSH and cortisol) both before and after 16 weeks of treatment. Under ALC administration hypo-LH patients showed a significant increase in LH plasma levels (from 1.4±0.3 to 3.1±0.5 mIU/ml, p<0.01) and in LH pulse amplitude (p<0.001). No changes were observed in the normo-LH group. LH response to naloxone was restored under ALC therapy. Maximal LH response and area under the curve under naloxone were significantly increased (p<0.05 and p<0.01, respectively). No changes were observed in the normo-LH patients. Our data support the hypothesis of a specific role of ALC on counteracting the stress-induced abnormalities in hypo-LH patients affected by hypothalamic amenorrhea.

  17. Negative energy balance in a male songbird, the Abert's towhee, constrains the testicular endocrine response to luteinizing hormone stimulation

    PubMed Central

    Davies, Scott; Gao, Sisi; Valle, Shelley; Bittner, Stephanie; Hutton, Pierce; Meddle, Simone L.; Deviche, Pierre

    2015-01-01

    ABSTRACT Energy deficiency can suppress reproductive function in vertebrates. As the orchestrator of reproductive function, endocrine activity of the hypothalamo-pituitary–gonadal (HPG) axis is potentially an important mechanism mediating such effects. Previous experiments in wild-caught birds found inconsistent relationships between energy deficiency and seasonal reproductive function, but these experiments focused on baseline HPG axis activity and none have investigated the responsiveness of this axis to endocrine stimulation. Here, we present data from an experiment in Abert's towhees, Melozone aberti, using gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) challenges to investigate whether energy deficiency modulates the plasma testosterone responsiveness of the HPG axis. Wild-caught birds were either ad libitum fed or energetically constrained via chronic food restriction during photoinduced reproductive development. Energy deficiency did not significantly affect the development of reproductive morphology, the baseline endocrine activity of the HPG axis, or the plasma testosterone response to GnRH challenge. Energy deficiency did, however, decrease the plasma testosterone responsiveness to LH challenge. Collectively, these observations suggest that energy deficiency has direct gonadal effects consisting of a decreased responsiveness to LH stimulation. Our study, therefore, reveals a mechanism by which energy deficiency modulates reproductive function in wild birds in the absence of detectable effects on baseline HPG axis activity. PMID:26333925

  18. Negative energy balance in a male songbird, the Abert's Towhee, constrains the testicular endocrine response to luteinizing hormone stimulation.

    PubMed

    Davies, Scott; Gao, Sisi; Valle, Shelley; Bittner, Stephanie; Hutton, Pierce; Meddle, Simone L; Deviche, Pierre

    2015-07-10

    Energy deficiency can suppress reproductive functions in vertebrates. As the orchestrator of reproductive function, endocrine activity of the hypothalamo-pituitary-gonadal (HPG) axis is potentially an important mechanism mediating such effects. Previous experiments in wild-caught birds found inconsistent relationships between energy deficiency and seasonal reproductive function, but these experiments focused on baseline HPG axis activity and none has investigated the responsiveness of this axis to endocrine stimulation. Here, we present data from an experiment in Abert's Towhees, Melozone aberti, using gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) challenges to investigate whether energy deficiency modulates the plasma testosterone (T) responsiveness of the HPG axis. Wild-caught birds were either ad libitum-fed or energetically constrained via chronic food restriction during photoinduced reproductive development. Energy deficiency did not significantly affect the development of reproductive morphology, the baseline endocrine activity of the HPG axis, or the plasma T response to GnRH challenge. Energy deficiency did, however, decrease the plasma T responsiveness to LH challenge. Collectively, these observations suggest that energy deficiency has direct gonadal effects consisting in decreased responsiveness to LH stimulation. Our study, therefore, reveals a mechanism by which energy deficiency modulates reproductive function in wild birds in the absence of detectable effects on baseline HPG axis activity. © 2015. Published by The Company of Biologists Ltd.

  19. Negative energy balance in a male songbird, the Abert's towhee, constrains the testicular endocrine response to luteinizing hormone stimulation.

    PubMed

    Davies, Scott; Gao, Sisi; Valle, Shelley; Bittner, Stephanie; Hutton, Pierce; Meddle, Simone L; Deviche, Pierre

    2015-09-01

    Energy deficiency can suppress reproductive function in vertebrates. As the orchestrator of reproductive function, endocrine activity of the hypothalamo-pituitary-gonadal (HPG) axis is potentially an important mechanism mediating such effects. Previous experiments in wild-caught birds found inconsistent relationships between energy deficiency and seasonal reproductive function, but these experiments focused on baseline HPG axis activity and none have investigated the responsiveness of this axis to endocrine stimulation. Here, we present data from an experiment in Abert's towhees, Melozone aberti, using gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) challenges to investigate whether energy deficiency modulates the plasma testosterone responsiveness of the HPG axis. Wild-caught birds were either ad libitum fed or energetically constrained via chronic food restriction during photoinduced reproductive development. Energy deficiency did not significantly affect the development of reproductive morphology, the baseline endocrine activity of the HPG axis, or the plasma testosterone response to GnRH challenge. Energy deficiency did, however, decrease the plasma testosterone responsiveness to LH challenge. Collectively, these observations suggest that energy deficiency has direct gonadal effects consisting of a decreased responsiveness to LH stimulation. Our study, therefore, reveals a mechanism by which energy deficiency modulates reproductive function in wild birds in the absence of detectable effects on baseline HPG axis activity. © 2015. Published by The Company of Biologists Ltd.

  20. The structure and thermal motion of the B800-850 LH2 complex from Rps.acidophila at 2.0A resolution and 100K: new structural features and functionally relevant motions.

    PubMed

    Papiz, Miroslav Z; Prince, Steve M; Howard, Tina; Cogdell, Richard J; Isaacs, Neil W

    2003-03-07

    The structure at 100K of integral membrane light-harvesting complex II (LH2) from Rhodopseudomonas acidophila strain 10050 has been refined to 2.0A resolution. The electron density has been significantly improved, compared to the 2.5A resolution map, by high resolution data, cryo-cooling and translation, libration, screw (TLS) refinement. The electron density reveals a second carotenoid molecule, the last five C-terminal residues of the alpha-chain and a carboxy modified alpha-Met1 which forms the ligand of the B800 bacteriochlorophyll. TLS refinement has enabled the characterisation of displacements between molecules in the complex. B850 bacteriochlorophyll molecules are arranged in a ring of 18 pigments composed of nine approximate dimers. These pigments are strongly coupled and at their equilibrium positions the excited state dipole interaction energies, within and between dimers, are approximately 370cm(-1) and 280cm(-1), respectively. This difference in coupling energy is similar in magnitude to changes in interaction energies arising from the pigment displacements described by TLS tensors. The displacements appear to be non-random in nature and appear to be designed to optimise the modulation of pigment energy interactions. This is the first time that LH2 pigment displacements have been quantified experimentally. The calculated energy changes indicate that there may be significant contributions to inter-pigment energy interactions from molecular displacements and these may be of importance to photosynthetic energy transfer.

  1. Spectroscopic and Thermodynamic Characterization of the Metal-Binding Sites in the LH1-RC Complex from Thermophilic Photosynthetic Bacterium Thermochromatium tepidum.

    PubMed

    Kimura, Yukihiro; Yura, Yuki; Hayashi, Yusuke; Li, Yong; Onoda, Moe; Yu, Long-Jiang; Wang-Otomo, Zheng-Yu; Ohno, Takashi

    2016-12-15

    The light-harvesting 1 reaction center (LH1-RC) complex from thermophilic photosynthetic bacterium Thermochromatium (Tch.) tepidum exhibits enhanced thermostability and an unusual LH1 Q y transition, both induced by Ca 2+ binding. In this study, metal-binding sites and metal-protein interactions in the LH1-RC complexes from wild-type (B915) and biosynthetically Sr 2+ -substituted (B888) Tch. tepidum were investigated by isothermal titration calorimetry (ITC), atomic absorption (AA), and attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopies. The ITC measurements revealed stoichiometric ratios of approximately 1:1 for binding of Ca 2+ , Sr 2+ , or Ba 2+ to the LH1 αβ-subunit, indicating the presence of 16 binding sites in both B915 and B888. The AA analysis provided direct evidence for Ca 2+ and Sr 2+ binding to B915 and B888, respectively, in their purified states. Metal-binding experiments supported that Ca 2+ and Sr 2+ (or Ba 2+ ) competitively associate with the binding sites in both species. The ATR-FTIR difference spectra upon Ca 2+ depletion and Sr 2+ substitution demonstrated that dissociation and binding of Ca 2+ are predominantly responsible for metal-dependent conformational changes of B915 and B888. The present results are largely compatible with the recent structural evidence that another binding site for Sr 2+ (or Ba 2+ ) exists in the vicinity of the Ca 2+ -binding site, a part of which is shared in both metal-binding sites.

  2. Nocturnal Urinary Excretion of FSH and LH in Children and Adolescents With Normal and Early Puberty.

    PubMed

    Kolby, Nanna; Busch, Alexander S; Aksglaede, Lise; Sørensen, Kaspar; Petersen, Jorgen Holm; Andersson, Anna-Maria; Juul, Anders

    2017-10-01

    Clinical use of single serum gonadotropin measurements in children is limited by the pulsatile secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). However, first morning voided (FMV) urine may integrate the fluctuating gonadotropin serum levels. We aimed to evaluate urinary and serum gonadotropin levels according to age, sex, and pubertal stage in healthy children and to assess the clinical use of FMV urinary gonadotropins in children with disordered puberty. Cross-sectional part of the COPENHAGEN Puberty Study and longitudinal study of patients. Population-based and outpatient clinic. Eight hundred forty-three healthy children from the COPENHAGEN Puberty Study and 25 girls evaluated for central precocious puberty (CPP). Clinical pubertal staging, including serum and urinary gonadotropin levels. Urinary gonadotropins increased with advancing age and pubertal development and were detectable in FMV urine before physical signs of puberty. FMV urinary LH correlated strongly with basal (r = 0.871, P < 0.001) and gonadotropin-releasing hormone (GnRH)-stimulated serum LH (r = 0.82, P < 0.001). Urinary LH was superior to urinary FSH in differentiating the pubertal stage. Receiver operating curve analysis revealed that a cut-off standard deviation (SD) score of 2 for urinary LH (IU/L) gave a sensitivity of 75% and a specificity of 92% in predicting a positive GnRH stimulation test (LHmax > 5 IU/L). Urinary concentrations of LH decreased after 3 months of GnRH treatment to levels below +2 SDs. Urinary gonadotropin levels increased before the onset of puberty and were elevated in girls with CPP. We suggest urinary LH as an alternative noninvasive method to improve diagnosing and therapeutic management of children with disordered puberty. Copyright © 2017 Endocrine Society

  3. Spectral and kinetic effects accompanying the assembly of core complexes of Rhodobacter sphaeroides.

    PubMed

    Freiberg, Arvi; Chenchiliyan, Manoop; Rätsep, Margus; Timpmann, Kõu

    2016-11-01

    In the present work, spectral and kinetic changes accompanying the assembly of the light-harvesting 1 (LH1) complex with the reaction center (RC) complex into monomeric RC-LH1 and dimeric RC-LH1-PufX core complexes of the photosynthetic purple bacterium Rhodobacter sphaeroides are systematically studied over the temperature range of 4.5-300K. The samples were interrogated with a combination of optical absorption, hole burning, fluorescence excitation, steady state and picosecond time resolved fluorescence spectroscopy. Fair additivity of the LH1 and RC absorption spectra suggests rather weak electronic coupling between them. A low-energy tail revealed at cryogenic temperatures in the absorption spectra of both monomeric and dimeric core complexes is proved to be due to the special pair of the RC. At selected excitation intensity and temperature, the fluorescence decay time of core complexes is shown to be a function of multiple factors, most importantly of the presence/absence of RCs, the supramolecular architecture (monomeric or dimeric) of the complexes, and whether the complexes were studied in a native membrane environment or in a detergent - purified state. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. [Construction and Characterization of B850-Only LH2 Energy Transfer System in Purple Bacteria].

    PubMed

    Li, Kai; Zhao, Chun-gui; Yue, Hui-ying; Yang, Su-ping; Qu, Yin-bo; Jiao, Nian-zhi

    2015-04-01

    To seek microscopic molecular mechanism of energy transfer and complex reconstitution in the photosynthesis, the conditions for construction of B850-only peripheral light-harvesting complex (LH2) and their properties were investigated using absorption, fluorescence spectroscopy, molecular sieve chromatography, ultrafiltration and sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) from the purple bacteria. The results indicated that bacteriochlorophylls (BChl) of B800 incubated in 10 mmo · L(-1) Tris-HCl (pH 8.0) buffer are selectively released from their binding sites of LH2 of Rhodobacter azotoformans (A-LH2) by 0.08% (W/V) SDS. B850-only A-LH2 was constructed after removing free BChl mixing with 10% methyl alcohol by ultrafiltration. B850 BChl was released after A-LH2 was incubated for 240 min in dark at room temperature (RT). While BChl of B800 incubated in pH 1.9 buffer were selectively released from their binding sites of LH2 of Rhodopseudomonas palustris (P-LH2). The authors acquired two components using molecular sieve chromatography. Free BChl of one component was not removed and self-assembled to P-LH2. The other removed free BChl and B850-only P-LH2 was constructed. B850 unchanged after P-LH2 was incubated. P-LH2 α and β subunits have different molecular weights, but those of A-LH2 are in the contrary. It is concluded that B850-only P-LH2 is more stable than A-LH2. The enigmatic split of the B800 absorption band was not observed in these LH2, but we acquired two kinds of B800-released LH2 from Rhodopseudomonas palustris. The authors' results may provide a new light to separate homogeneous Apoprotein LH2.

  5. Disentangling mechanisms involved in collagen pyridinoline cross-linking: The immunophilin FKBP65 is critical for dimerization of lysyl hydroxylase 2

    PubMed Central

    Gjaltema, Rutger A. F.; van der Stoel, Miesje M.; Boersema, Miriam; Bank, Ruud A.

    2016-01-01

    Collagens are subjected to extensive posttranslational modifications, such as lysine hydroxylation. Bruck syndrome (BS) is a connective tissue disorder characterized at the molecular level by a loss of telopeptide lysine hydroxylation, resulting in reduced collagen pyridinoline cross-linking. BS results from mutations in the genes coding for lysyl hydroxylase (LH) 2 or peptidyl-prolyl cis-trans isomerase (PPIase) FKBP65. Given that the immunophilin FKBP65 does not exhibit LH activity, it is likely that LH2 activity is somehow dependent on FKPB65. In this report, we provide insights regarding the interplay between LH2 and FKBP65. We found that FKBP65 forms complexes with LH2 splice variants LH2A and LH2B but not with LH1 and LH3. Ablating the catalytic activity of FKBP65 or LH2 did not affect complex formation. Both depletion of FKBP65 and inhibition of FKBP65 PPIase activity reduced the dimeric (active) form of LH2 but did not affect the binding of monomeric (inactive) LH2 to procollagen Iα1. Furthermore, we show that LH2A and LH2B cannot form heterodimers with each other but are able to form heterodimers with LH1 and LH3. Collectively, our results indicate that FKBP65 is linked to pyridinoline cross-linking by specifically mediating the dimerization of LH2. Moreover, FKBP65 does not interact with LH1 and LH3, explaining why in BS triple-helical hydroxylysines are not affected. Our results provide a mechanistic link between FKBP65 and the loss of pyridinolines and may hold the key to future treatments for diseases related to collagen cross-linking anomalies, such as fibrosis and cancer. PMID:27298363

  6. Epigenetic regulation of BDNF in the learned helplessness-induced animal model of depression.

    PubMed

    Su, Chun-Lin; Su, Chun-Wei; Hsiao, Ya-Hsin; Gean, Po-Wu

    2016-05-01

    Major depressive disorder (MDD), one of the most common mental disorders, is a significant risk factor for suicide and causes a low quality of life for many people. However, the causes and underlying mechanism of depression remain elusive. In the current work, we investigated epigenetic regulation of BDNF in the learned helplessness-induced animal model of depression. Mice were exposed to inescapable stress and divided into learned helplessness (LH) and resilient (LH-R) groups depending on the number they failed to escape. We found that the LH group had longer immobility duration in the forced swimming test (FST) and tail suspension tests (TST), which is consistent with a depression-related phenotype. Western blotting analysis and enzyme-linked immunosorbent assay (ELISA) revealed that the LH group had lower BDNF expression than that of the LH-R group. The LH group consistently had lower BDNF mRNA levels, as detected by qPCR assay. In addition, we found BDNF exon IV was down-regulated in the LH group. Intraperitoneal injection of imipramine or histone deacetylase inhibitors (HDACi) to the LH mice for 14 consecutive days ameliorated depression-like behaviors and reversed the decrease in BDNF. The expression of HDAC5 was up-regulated in the LH mice, and a ChIP assay revealed that the level of HDAC5 binding to the promoter region of BDNF exon IV was higher than that seen in other groups. Knockdown of HDAC5 reduced depression-like behaviors in the LH mice. Taken together, these results suggest that epigenetic regulation of BDNF by HDAC5 plays an important role in the learned helplessness model of depression. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Serum androgen levels in women who have recurrent miscarriages and their correlation with markers of endometrial function.

    PubMed

    Okon, M A; Laird, S M; Tuckerman, E M; Li, T C

    1998-04-01

    To compare plasma androgen concentrations in women who have recurrent miscarriages and in fertile women, and to correlate the results with concentrations of the endometrial protein PP14 in uterine flushings and plasma from women who have recurrent miscarriages. Retrospective study. Hospital research unit. Women attending a recurrent miscarriage clinic and normal fertile volunteers. Ten of the women with recurrent miscarriages had polycystic ovary disease (PCOD) as assessed by ultrasonography or increased follicular LH levels. Plasma samples were obtained from the women on days LH-7, LH-4, LH+0, and LH+7 or LH+10 of a cycle. An endometrial flushing sample and a biopsy specimen were taken from women with recurrent miscarriages on day LH+7 or LH+10. Androstenedione, testosterone, and sex hormone-binding globulin (SHBG) were measured in the plasma samples. The endometrial protein PP14 was measured in the uterine flushings and in the LH+7 or LH+10 plasma samples from the women with recurrent miscarriages. Testosterone concentrations were higher in the women with recurrent miscarriages both with and without PCOD on days LH-7 and LH-4 of the cycle. Concentrations of androstenedione also were higher in the women with recurrent miscarriages, but without PCOD on day LH-7. Testosterone SHBG ratios were higher in the women with recurrent miscarriages, without PCOD compared with the controls on days LH-7, LH+0, and LH+7. Mean follicular testosterone concentrations were correlated negatively with both uterine (r = -0.47) and plasma (r = -0.49) PP14 levels on day LH+10. Mean luteal phase testosterone SHBG ratios were correlated negatively with uterine PP14 concentrations on day LH+7 of the cycle (r = -0.674). Androgen levels are higher in women who have recurrent miscarriages than in normal fertile controls. These high levels of androgens may have a detrimental effect on endometrial function.

  8. In Vitro Self-Assembly of the Light Harvesting Pigment-Protein LH2 Revealed by Ultrafast Spectroscopy and Electron Microscopy

    PubMed Central

    Schubert, Axel; Stenstam, Anna; Beenken, Wichard J. D.; Herek, Jennifer L.; Cogdell, Richard; Pullerits, Tõnu; Sundström, Villy

    2004-01-01

    Controlled ensemble formation of protein-surfactant systems provides a fundamental concept for the realization of nanoscale devices with self-organizing capability. In this context, spectroscopic monitoring of pigment-containing proteins yields detailed structural information. Here we have studied the association behavior of the bacterial light-harvesting protein LH2 from Rhodobacter spheroides in an n,n-dimethyldodecylamine-n-oxide/water environment. Time-resolved studies of the excitation annihilation yielded information about aggregate sizes and packing of the protein complexes therein. The results are compared to transmission electron microscopy images of instantaneously frozen samples. Our data indicate the manifestation of different phases, which are discussed with respect to the thermodynamic equilibrium in ternary protein-surfactant-water systems. Accordingly, by varying the concentration the formation of different types of aggregates can be controlled. Conditions for the appearance of isolated LH2 complexes are defined. PMID:15041674

  9. Effects of centrifugation stress on pituitary-gonadal function in male rats

    NASA Technical Reports Server (NTRS)

    Gray, G. D.; Smith, E. R.; Damassa, D. A.; Davidson, J. M.

    1980-01-01

    The effects of centrifugation for various lengths of time on circulating levels of luteinizing hormone (LH) and testosterone in male rats were investigated. In a chronic 52-day experiment, centrifugation at 4.1 G significantly reduced LH and testosterone levels for the entire period. Centrifugation at 2.3 G had less effect inasmuch as LH levels were not significantly decreased and testosterone levels were significantly reduced only during the first few days of centrifugation. In more acute experiments, centrifugation at 4.1 G for 4 h resulted in reduced testosterone levels, whereas centrifugation for 15 min did not significantly alter the hormone levels. These results indicate that centrifugation can decrease circulating LH and testosterone levels if the gravitational force is of sufficient magnitude and is maintained for a period of hours. Chronic centrifugation may also inhibit the acute excitatory response of LH to handling and ether stress.

  10. Neuromedin s as novel putative regulator of luteinizing hormone secretion.

    PubMed

    Vigo, E; Roa, J; López, M; Castellano, J M; Fernandez-Fernandez, R; Navarro, V M; Pineda, R; Aguilar, E; Diéguez, C; Pinilla, L; Tena-Sempere, M

    2007-02-01

    Neuromedin S (NMS), a 36 amino acid peptide structurally related to neuromedin U, was recently identified in rat brain as ligand for the G protein-coupled receptor FM4/TGR-1, also termed neuromedin U receptor type-2 (NMU2R). Central expression of NMS appears restricted to the suprachiasmatic nucleus, and NMS has been involved in the regulation of dark-light rhythms and suppression of food intake. Reproduction is known to be tightly regulated by metabolic and photoperiodic cues. Yet the potential contribution of NMS to the control of reproductive axis remains unexplored. We report herein analyses of hypothalamic expression of NMS and NMU2R genes, as well as LH responses to NMS, in different developmental and functional states of the female rat. Expression of NMS and NMU2R genes was detected at the hypothalamus along postnatal development, with significant fluctuations of their relative levels (maximum at prepubertal stage and adulthood). In adult females, hypothalamic expression of NMS (which was confined to suprachiasmatic nucleus) and NMU2R significantly varied during the estrous cycle (maximum at proestrus) and was lowered after ovariectomy and enhanced after progesterone supplementation. Central administration of NMS evoked modest LH secretory responses in pubertal and cyclic females at diestrus, whereas exaggerated LH secretory bursts were elicited by NMS at estrus and after short-term fasting. Conversely, NMS significantly decreased elevated LH concentrations of ovariectomized rats. In summary, we provide herein novel evidence for the ability of NMS to modulate LH secretion in the female rat. Moreover, hypothalamic expression of NMS and NMU2R genes appeared dependent on the functional state of the female reproductive axis. Our data are the first to disclose the potential implication of NMS in the regulation of gonadotropic axis, a function that may contribute to the integration of circadian rhythms, energy balance, and reproduction.

  11. Decreased expression of lysyl hydroxylase 2 (LH2) in skin fibroblasts from three Ehlers-Danlos patients does not result from mutations in either the coding or proximal promoter region of the LH2 gene.

    PubMed

    Walker, L C; Teebi, A S; Marini, J C; De Paepe, A; Malfait, F; Atsawasuwan, P; Yamauchi, M; Yeowell, H N

    2004-12-01

    The Ehlers-Danlos syndromes (EDS) are a heterogeneous group of inherited connective tissue disorders characterized by tissue fragility, hyperelasticity of the skin and joint hypermobility. This phenotype, accompanied by kyphoscoliosis and/or ocular fragility, is present in patients with the autosomal recessive type VI form of EDS. These patients have significantly decreased levels of lysyl hydroxylase (LH) activity, due to mutations in the LH1 gene. LH hydroxylates specific lysine residues in the collagen molecule that are precursors for the formation of cross-links which provide collagen with its tensile strength. No disorder has been directly linked to decreased expression of LH2 and LH3, two other isoforms of LH. This study describes 3 patients with mixed phenotypes of EDS, who have significantly decreased mRNAs for LH2, but normal levels of LH1 and LH3 mRNAs, in their skin fibroblasts. In contrast to the effect of LH1 deficiency in EDS VI patients, the decreased expression of LH2 does not affect LH activity, bifunctional collagen cross-links (measured after reduction as dihydroxylysinonorleucine (DHLNL) and hydroxylysinonorleucine (HLNL)), or helical lysine hydroxylation in these cell lines. Sequence analysis of full length LH2 cDNAs and 1kb of the promoter region of LH2 does not show mutations that could explain the decreased expression of LH2. These results suggest that the deficiency of LH2 in these fibroblasts may be caused by changes in other factors required for the expression of LH2.

  12. An orexinergic projection from perifornical hypothalamus to raphe pallidus increases rat brown adipose tissue thermogenesis.

    PubMed

    Tupone, Domenico; Madden, Christopher J; Cano, Georgina; Morrison, Shaun F

    2011-11-02

    Orexin (hypocretin) neurons, located exclusively in the PeF-LH, which includes the perifornical area (PeF), the lateral hypothalamus (LH), and lateral portions of the medial hypothalamus, have widespread projections and influence many physiological functions, including the autonomic regulation of body temperature and energy metabolism. Narcolepsy is characterized by the loss of orexin neurons and by disrupted sleep, but also by dysregulation of body temperature and by a strong tendency for obesity. Heat production (thermogenesis) in brown adipose tissue (BAT) contributes to the maintenance of body temperature and, through energy consumption, to body weight regulation. We identified a neural substrate for the influence of orexin neurons on BAT thermogenesis in rat. Nanoinjection of orexin-A (12 pmol) into the rostral raphe pallidus (rRPa), the site of BAT sympathetic premotor neurons, produced large, sustained increases in BAT sympathetic outflow and in BAT thermogenesis. Activation of neurons in the PeF-LH also enhanced BAT thermogenesis over a long time course. Combining viral retrograde tracing from BAT, or cholera toxin subunit b tracing from rRPa, with orexin immunohistochemistry revealed synaptic connections to BAT from orexin neurons in PeF-LH and from rRPa neurons with closely apposed, varicose orexin fibers, as well as a direct, orexinergic projection from PeF-LH to rRPa. These results indicate a potent modulation of BAT thermogenesis by orexin released from the terminals of orexin neurons in PeF-LH directly into the rRPa and provide a potential mechanism contributing to the disrupted regulation of body temperature and energy metabolism in the absence of orexin.

  13. Fluorescence polarization measures energy funneling in single light-harvesting antennas—LH2 vs conjugated polymers

    PubMed Central

    Camacho, Rafael; Tubasum, Sumera; Southall, June; Cogdell, Richard J.; Sforazzini, Giuseppe; Anderson, Harry L.; Pullerits, Tõnu; Scheblykin, Ivan G.

    2015-01-01

    Numerous approaches have been proposed to mimic natural photosynthesis using artificial antenna systems, such as conjugated polymers (CPs), dendrimers, and J-aggregates. As a result, there is a need to characterize and compare the excitation energy transfer (EET) properties of various natural and artificial antennas. Here we experimentally show that EET in single antennas can be characterized by 2D polarization imaging using the single funnel approximation. This methodology addresses the ability of an individual antenna to transfer its absorbed energy towards a single pool of emissive states, using a single parameter called energy funneling efficiency (ε). We studied individual peripheral antennas of purple bacteria (LH2) and single CP chains of 20 nm length. As expected from a perfect antenna, LH2s showed funneling efficiencies close to unity. In contrast, CPs showed lower average funneling efficiencies, greatly varying from molecule to molecule. Cyclodextrin insulation of the conjugated backbone improves EET, increasing the fraction of CPs possessing ε = 1. Comparison between LH2s and CPs shows the importance of the protection systems and the protein scaffold of LH2, which keep the chromophores in functional form and at such geometrical arrangement that ensures excellent EET. PMID:26478272

  14. Molecular association of 2-(n-alkylamino)-1,4-naphthoquinone derivatives: Electrochemical, DFT studies and antiproliferative activity against leukemia cell lines

    NASA Astrophysics Data System (ADS)

    Patil, Rishikesh; Bhand, Sujit; Konkimalla, V. Badireenath; Banerjee, Priyabrata; Ugale, Bharat; Chadar, Dattatray; Saha, Sourav Kr.; Praharaj, Prakash Priyadarshi; Nagaraja, C. M.; Chakrovarty, Debamitra; Salunke-Gawali, Sunita

    2016-12-01

    Molecular structures and their molecular association of 2-(n-alkylamino)-1,4-naphthoquinone, viz., LH-3; propyl, LH-4; butyl and LH-8; octyl derivatives were studied by single crystal X-ray diffraction studies. Synthesis and characterization of 2-octylamino-1,4-naphthoquinone; LH-8 was discussed. The molecule of LH-3 crystallizes in orthorhombic space group P21/c, while the LH-4 and LH-8 molecule crystallizes in triclinic space group P-1. LH-3, LH-4 and LH-8 showed intermolecular N-H⋯O and C-H⋯O interactions, LH-3 showed unique C(3)-H(3)⋯O(1) interaction. Interchain π-π stacking, slipped π-π stacking and C⋯O close contacts was respectively observed in LH-3, LH-4 and LH-8. Electrochemical studies were performed on first eight members of homologous series of 2-(n-alkylamino)-1,4-naphthoquinone (LH-1 to LH-8) by cyclic voltammetry. Naphthoquinone to naphthosemiquinone reversible redox couple was observed in all compounds ∼ E1/2 = -0.657 ± 0.05 V. HOMO-LUMO band gap was determined for the neutral form as well as the monoanionic radical form viz. naphthosemiquinone form of selected derivatives by DFT studies. It has been observed that the electron density is delocalized in the naphthoquinone ring in both neutral as well as one electron reduced form of compounds. Antiproliferative activity of LH-1 to LH-8 was evaluated against two cancer cell lines, THP1(acute monocytic leukemia) and K562(human immortalized myelogenous leukemia cell line) cells. It was observed that, in THP1 cells, compounds LH-2 and LH-3 are very active while LH-1, LH-4 and LH-6 were moderately active and LH-5, LH-7 and LH-8 were totally inactive. Contrastingly, in K562 cells all of the compounds were moderately active.

  15. Highly potent antagonists of luteinizing hormone-releasing hormone free of edematogenic effects.

    PubMed

    Bajusz, S; Kovacs, M; Gazdag, M; Bokser, L; Karashima, T; Csernus, V J; Janaky, T; Guoth, J; Schally, A V

    1988-03-01

    To eliminate the undesirable edematogenic effect of the luteinizing hormone-releasing hormone (LH-RH) antagonists containing basic D amino acids at position 6, exemplified by [Ac-D-Phe(pCl)1,2,D-Trp3,D-Arg6,D-Ala10]LH-RH [Phe(pCl) indicates 4-chlorophenylalanine], analogs with D-ureidoalkyl amino acids such as D-citrulline (D-Cit) or D-homocitrulline (D-Hci) at position 6 were synthesized and tested in several systems in vitro and in vivo. HPLC analysis revealed that the overall hydrophobicity of the D-Cit/D-Hci6 analogs was similar to that of the basic D-Arg6 antagonists. In vitro, most of the analogs completely inhibited LH-RH-mediated luteinizing hormone release in perfused rat pituitary cell systems at an antagonist to LH-RH molar ratio of 5:1. In vivo, the most active peptides, [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Trp3,D-Cit6,D-Ala10]LH-RH [Nal(2) indicates 3-(2-naphthyl)alanine] and its D-Hci6 analog, caused 100% inhibition of ovulation in cycling rats in doses of 3 micrograms and suppressed the luteinizing hormone level in ovariectomized female rats for 47 hr when administered at doses of 25 micrograms. Characteristically, these peptides did not exert any edematogenic effects even at 1.5 mg/kg. These properties of the D-Cit/D-Hci6 antagonists may make them useful clinically.

  16. Highly potent antagonists of luteinizing hormone-releasing hormone free of edematogenic effects.

    PubMed Central

    Bajusz, S; Kovacs, M; Gazdag, M; Bokser, L; Karashima, T; Csernus, V J; Janaky, T; Guoth, J; Schally, A V

    1988-01-01

    To eliminate the undesirable edematogenic effect of the luteinizing hormone-releasing hormone (LH-RH) antagonists containing basic D amino acids at position 6, exemplified by [Ac-D-Phe(pCl)1,2,D-Trp3,D-Arg6,D-Ala10]LH-RH [Phe(pCl) indicates 4-chlorophenylalanine], analogs with D-ureidoalkyl amino acids such as D-citrulline (D-Cit) or D-homocitrulline (D-Hci) at position 6 were synthesized and tested in several systems in vitro and in vivo. HPLC analysis revealed that the overall hydrophobicity of the D-Cit/D-Hci6 analogs was similar to that of the basic D-Arg6 antagonists. In vitro, most of the analogs completely inhibited LH-RH-mediated luteinizing hormone release in perfused rat pituitary cell systems at an antagonist to LH-RH molar ratio of 5:1. In vivo, the most active peptides, [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Trp3,D-Cit6,D-Ala10]LH-RH [Nal(2) indicates 3-(2-naphthyl)alanine] and its D-Hci6 analog, caused 100% inhibition of ovulation in cycling rats in doses of 3 micrograms and suppressed the luteinizing hormone level in ovariectomized female rats for 47 hr when administered at doses of 25 micrograms. Characteristically, these peptides did not exert any edematogenic effects even at 1.5 mg/kg. These properties of the D-Cit/D-Hci6 antagonists may make them useful clinically. PMID:3278323

  17. Ultrafast time-resolved carotenoid to-bacteriochlorophyll energy transfer in LH2 complexes from photosynthetic bacteria.

    PubMed

    Cong, Hong; Niedzwiedzki, Dariusz M; Gibson, George N; LaFountain, Amy M; Kelsh, Rhiannon M; Gardiner, Alastair T; Cogdell, Richard J; Frank, Harry A

    2008-08-28

    Steady-state and ultrafast time-resolved optical spectroscopic investigations have been carried out at 293 and 10 K on LH2 pigment-protein complexes isolated from three different strains of photosynthetic bacteria: Rhodobacter (Rb.) sphaeroides G1C, Rb. sphaeroides 2.4.1 (anaerobically and aerobically grown), and Rps. acidophila 10050. The LH2 complexes obtained from these strains contain the carotenoids, neurosporene, spheroidene, spheroidenone, and rhodopin glucoside, respectively. These molecules have a systematically increasing number of pi-electron conjugated carbon-carbon double bonds. Steady-state absorption and fluorescence excitation experiments have revealed that the total efficiency of energy transfer from the carotenoids to bacteriochlorophyll is independent of temperature and nearly constant at approximately 90% for the LH2 complexes containing neurosporene, spheroidene, spheroidenone, but drops to approximately 53% for the complex containing rhodopin glucoside. Ultrafast transient absorption spectra in the near-infrared (NIR) region of the purified carotenoids in solution have revealed the energies of the S1 (2(1)Ag-)-->S2 (1(1)Bu+) excited-state transitions which, when subtracted from the energies of the S0 (1(1)Ag-)-->S2 (1(1)Bu+) transitions determined by steady-state absorption measurements, give precise values for the positions of the S1 (2(1)Ag-) states of the carotenoids. Global fitting of the ultrafast spectral and temporal data sets have revealed the dynamics of the pathways of de-excitation of the carotenoid excited states. The pathways include energy transfer to bacteriochlorophyll, population of the so-called S* state of the carotenoids, and formation of carotenoid radical cations (Car*+). The investigation has found that excitation energy transfer to bacteriochlorophyll is partitioned through the S1 (1(1)Ag-), S2 (1(1)Bu+), and S* states of the different carotenoids to varying degrees. This is understood through a consideration of the energies of the states and the spectral profiles of the molecules. A significant finding is that, due to the low S1 (2(1)Ag-) energy of rhodopin glucoside, energy transfer from this state to the bacteriochlorophylls is significantly less probable compared to the other complexes. This work resolves a long-standing question regarding the cause of the precipitous drop in energy transfer efficiency when the extent of pi-electron conjugation of the carotenoid is extended from ten to eleven conjugated carbon-carbon double bonds in LH2 complexes from purple photosynthetic bacteria.

  18. Fifty-ninth Christmas Bird Count. 176. Ocean City, Md

    USGS Publications Warehouse

    Rattner, B.A.; Michael, S.D.

    1983-01-01

    Some organophosphorus insecticides have been reported to interfere with reproduction and even cause the decline of small mammal populations. The effects of such anticholinesterases on plasma LH concentrations were examined in male mice (Peromyscus leucopus noveboracensis) intubated with water (OW) or acephate (50 and 100 mg/kg) and sacrificed after 4 h. Brain acetylcholinesterase (AChE) activity was inhibited by 45 and 56%, and basal LH levels were reduced by 29 and 25% in mice receiving the 2 doses of acephate. Responsiveness to LHRH did not appear to be affected 4 h after intubation with 100 mg/kg acephate, as 5 ug/kg LHRH ip evoked a comparable rise in plasma LH after 30 min (2.4 and 3.6 fold) in OW-control and treated mice. Subchronic dietary exposure to 0, 25, 100, and 400 ppm acephate for 5 days resulted in a dose-dependent decline in brain AChE activity (23, 42, and 57%), but did not affect LH concentration or the weights of testes and seminal vesicles. These findings suggest that acute exposure to organophosphorus insecticides may impair reproductive function by altering LH secretion.

  19. Absorption spectral change of peripheral-light harvesting complexes 2 induced by magnesium protoporphyrin IX monomethyl ester association

    NASA Astrophysics Data System (ADS)

    Yue, Huiying; Zhao, Chungui; Li, Kai; Yang, Suping

    2015-02-01

    Several spectrally different types of peripheral light harvesting complexes (LH) have been reported in anoxygenic phototrophic bacteria in response to environmental changes. In this study, two spectral forms of LH2 (T-LH2 and U-LH2) were isolated from Rhodobacter azotoformans. The absorption of T-LH2 was extremely similar to the LH2 isolated from Rhodobacter sphaeroides. U-LH2 showed an extra peak at ∼423 nm in the carotenoid region. To explore the spectral origin of this absorption peak, the difference in pigment compositions of two LH2 was analyzed. Spheroidene and bacteriochlorophyll aP were both contained in the two LH2. And magnesium protoporphyrin IX monomethyl ester (MPE) was only contained in U-LH2. It is known that spheroidene and bacteriochlorophyll aP do not produce ∼423 nm absorption peak either in vivo or in vitro. Whether MPE accumulation was mainly responsible for the formation of the ∼423 nm peak? The interactions between MPE and different proteins were further studied. The results showed that the maximum absorption of MPE was red-shifted from ∼415 nm to ∼423 nm when it was mixed with T-LH2 and its apoproteins, nevertheless, the Qy transitions of the bound bacteriochlorophylls in LH2 were almost unaffected, which indicated that the formation of the ∼423 nm peak was related to MPE-LH2 protein interaction. MPE did not bind to sites involved in the spectral tuning of BChls, but the conformation of integral LH2 was affected by MPE association, the alkaline stability of U-LH2 was lower than T-LH2, and the fluorescence intensity at 860 nm was decreased after MPE combination.

  20. Absorption spectral change of peripheral-light harvesting complexes 2 induced by magnesium protoporphyrin IX monomethyl ester association.

    PubMed

    Yue, Huiying; Zhao, Chungui; Li, Kai; Yang, Suping

    2015-02-25

    Several spectrally different types of peripheral light harvesting complexes (LH) have been reported in anoxygenic phototrophic bacteria in response to environmental changes. In this study, two spectral forms of LH2 (T-LH2 and U-LH2) were isolated from Rhodobacter azotoformans. The absorption of T-LH2 was extremely similar to the LH2 isolated from Rhodobacter sphaeroides. U-LH2 showed an extra peak at ∼423 nm in the carotenoid region. To explore the spectral origin of this absorption peak, the difference in pigment compositions of two LH2 was analyzed. Spheroidene and bacteriochlorophyll aP were both contained in the two LH2. And magnesium protoporphyrin IX monomethyl ester (MPE) was only contained in U-LH2. It is known that spheroidene and bacteriochlorophyll aP do not produce ∼423 nm absorption peak either in vivo or in vitro. Whether MPE accumulation was mainly responsible for the formation of the ∼423 nm peak? The interactions between MPE and different proteins were further studied. The results showed that the maximum absorption of MPE was red-shifted from ∼415 nm to ∼423 nm when it was mixed with T-LH2 and its apoproteins, nevertheless, the Qy transitions of the bound bacteriochlorophylls in LH2 were almost unaffected, which indicated that the formation of the ∼423 nm peak was related to MPE-LH2 protein interaction. MPE did not bind to sites involved in the spectral tuning of BChls, but the conformation of integral LH2 was affected by MPE association, the alkaline stability of U-LH2 was lower than T-LH2, and the fluorescence intensity at 860 nm was decreased after MPE combination. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Cisplatin Binding to Biological Ligands Revealed at the Encounter Complex Level by IR Action Spectroscopy.

    PubMed

    Corinti, Davide; Coletti, Cecilia; Re, Nazzareno; Chiavarino, Barbara; Crestoni, Maria Elisa; Fornarini, Simonetta

    2016-03-07

    Cisplatin [cis-diamminedichloroplatinum(II)] was the first platinum-based antineoplastic agent and is still a cornerstone for the treatment of various solid tumors. Reactive events responsible for cisplatin activity are unveiled here at the molecular level. Simple ligands (L) representing ubiquitous functional groups in the biological environment likely to be encountered by administered cisplatin have been allowed to react with cis-[PtCl(NH3)2 (H2O)](+), the primary intermediate from cisplatin hydrolysis. The substitution reactions have been examined by a combined experimental and computational approach and the structural features of the substitution product, cis-[PtCl(NH3)2(L)](+), have been probed by IR multiple-photon dissociation (IRMPD) spectroscopy. Furthermore, IRMPD spectroscopy has been exploited to elucidate the structure of [PtCl(NH3)2(L)(H2O)](+) clusters, also obtained by electrospray ionization (ESI) from the aqueous solution and representing the major focus of this investigation. These ions conform to the encounter complex of cis-[PtCl(NH3)2 (H2O)](+) with the incoming ligand and represent the first direct evidence of a prototypical Eigen-Wilkins encounter complex in solution, lying on the reaction coordinate for ligand substitution and extracted by ESI for mass spectrometric analysis. Activated [PtCl(NH3)2(L)(H2O)](+) ions dissociate by the loss of either H2O or L, the former process implying a ligand substitution event. IRMPD spectroscopy has thus revealed both structural details and reaction dynamics at the level of the isolated encounter complex. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Microbial communities from different subsystems in biological heap leaching system play different roles in iron and sulfur metabolisms.

    PubMed

    Xiao, Yunhua; Liu, Xueduan; Ma, Liyuan; Liang, Yili; Niu, Jiaojiao; Gu, Yabing; Zhang, Xian; Hao, Xiaodong; Dong, Weiling; She, Siyuan; Yin, Huaqun

    2016-08-01

    The microbial communities are important for minerals decomposition in biological heap leaching system. However, the differentiation and relationship of composition and function of microbial communities between leaching heap (LH) and leaching solution (LS) are still unclear. In this study, 16S rRNA gene sequencing was used to assess the microbial communities from the two subsystems in ZiJinShan copper mine (Fujian province, China). Results of PCoA and dissimilarity test showed that microbial communities in LH samples were significantly different from those in LS samples. The dominant genera of LH was Acidithiobacillus (57.2 ∼ 87.9 %), while Leptospirillum (48.6 ∼ 73.7 %) was predominant in LS. Environmental parameters (especially pH) were the major factors to influence the composition and structure of microbial community by analysis of Mantel tests. Results of functional test showed that microbial communities in LH utilized sodium thiosulfate more quickly and utilized ferrous sulfate more slowly than those in LS, which further indicated that the most sulfur-oxidizing processes of bioleaching took place in LH and the most iron-oxidizing processes were in LS. Further study found that microbial communities in LH had stronger pyrite leaching ability, and iron extraction efficiency was significantly positively correlated with Acidithiobacillus (dominated in LH), which suggested that higher abundance ratio of sulfur-oxidizing microbes might in favor of minerals decomposition. Finally, a conceptual model was designed through the above results to better exhibit the sulfur and iron metabolism in bioleaching systems.

  3. Short-term estriol administration modulates hypothalamo-pituitary function in patients with functional hypothalamic amenorrhea (FHA).

    PubMed

    Genazzani, Alessandro D; Podfigurna-Stopa, Agnieszka; Czyzyk, Adam; Katulski, Krzysztof; Prati, Alessia; Despini, Giulia; Angioni, Stefano; Simoncini, Tommaso; Meczekalski, Blazej

    2016-01-01

    To evaluate the influence of short-term estriol administration (10 d) on the hypothalamus-pituitary function and gonadotropins secretion in patients affected by functional hypothalamic amenorrhea (FHA). Controlled clinical study on patients with FHA (n = 12) in a clinical research environment. Hormonal determinations and gonadotropin (luteinizing hormone [LH] and FSH) response to a gonadotropin-releasing hormone (GnRH) bolus (10 μg) at baseline condition and after 10 d of therapy with 2 mg/d of estriol per os. Measurements of plasma LH, FSH, prolactin, estradiol, androstenedione, 17α-hydroxyprogesterone, insulin, cortisol, thyroid-stimulating hormone, free triiodothyronine, and free thyroxine. After treatment, the FHA patients showed a statistically significant increase of both LH and FSH plasma levels and the significant increase of their responses to the GnRH bolus. Estriol short-term therapy modulates within 10 d of administration the neuroendocrine control of the hypothalamus-pituitary unit and induces the recovery of both gonadotropins synthesis and secretion in hypogonadotropic patients with FHA.

  4. Early effects of cranial irradiation on hypothalamic-pituitary function

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lam, K.S.; Tse, V.K.; Wang, C.

    1987-03-01

    Hypothalamic-pituitary function was studied in 31 patients before and after cranial irradiation for nasopharyngeal carcinoma. The estimated radiotherapy (RT) doses to the hypothalamus and pituitary were 3979 +/- 78 (+/- SD) and 6167 +/- 122 centiGrays, respectively. All patients had normal pituitary function before RT. One year after RT, there was a significant decrease in the integrated serum GH response to insulin-induced hypoglycemia. In the male patients, basal serum FSH significantly increased, while basal serum LH and testosterone did not change. Moreover, in response to LHRH, the integrated FSH response was increased while that of LH was decreased. Such discordantmore » changes in FSH and LH may be explained by a defect in LHRH pulsatile release involving predominantly a decrease in pulse frequency. The peak serum TSH response to TRH became delayed in 28 patients, suggesting a defect in TRH release. Twenty-one patients were reassessed 2 yr after RT. Their mean basal serum T4 and plasma cortisol levels had significantly decreased. Hyperprolactinemia associated with oligomenorrhoea was found in 3 women. Further impairment in the secretion of GH, FSH, LH, TSH, and ACTH had occurred, and 4 patients had hypopituitarism. Thus, progressive impairment in hypothalamic-pituitary function occurs after cranial irradiation and can be demonstrated as early as 1 yr after RT.« less

  5. Human LH and hCG stimulate differently the early signalling pathways but result in equal testosterone synthesis in mouse Leydig cells in vitro.

    PubMed

    Riccetti, Laura; De Pascali, Francesco; Gilioli, Lisa; Potì, Francesco; Giva, Lavinia Beatrice; Marino, Marco; Tagliavini, Simonetta; Trenti, Tommaso; Fanelli, Flaminia; Mezzullo, Marco; Pagotto, Uberto; Simoni, Manuela; Casarini, Livio

    2017-01-05

    Human luteinizing hormone (LH) and chorionic gonadotropin (hCG) are glycoprotein hormones regulating development and reproductive functions by acting on the same receptor (LHCGR). We compared the LH and hCG activity in gonadal cells from male mouse in vitro, i.e. primary Leydig cells, which is a common tool used for gonadotropin bioassay. Murine Leydig cells are naturally expressing the murine LH receptor (mLhr), which binds human LH/hCG. Cultured Leydig cells were treated by increasing doses of recombinant LH and hCG, and cell signaling, gene expression and steroid synthesis were evaluated. We found that hCG is about 10-fold more potent than LH in cAMP recruitment, and slightly but significantly more potent on cAMP-dependent Erk1/2 phosphorylation. However, no significant differences occur between LH and hCG treatments, measured as activation of downstream signals, such as Creb phosphorylation, Stard1 gene expression and testosterone synthesis. These data demonstrate that the responses to human LH/hCG are only quantitatively and not qualitatively different in murine cells, at least in terms of cAMP and Erk1/2 activation, and equal in activating downstream steroidogenic events. This is at odds with what we previously described in human primary granulosa cells, where LHCGR mediates a different pattern of signaling cascades, depending on the natural ligand. This finding is relevant for gonadotropin quantification used in the official pharmacopoeia, which are based on murine, in vivo bioassay and rely on the evaluation of long-term, testosterone-dependent effects mediated by rodent receptor.

  6. The Reconstruction and Failure Analysis of The Space Shuttle Columbia

    NASA Technical Reports Server (NTRS)

    Russell, Richard W.

    2010-01-01

    This viewgraph presentation describes a very detailed reconstruction plan and failure analysis of The Space Shuttle Columbia accident. The contents include: 1) STS-107 Timeline; 2) Foam Impact; 3) Recovery; 4) Reconstruction; 5) Reconstruction Plan; 6) Reconstruction Hanger; 7) Pathfinders; 8) Aluminum Pathfinder; 9) Early Analysis - Left MLG Door Area; 10) Emphasis Switched to Left Hand Wing Leading Edge; 11) Wing Leading Edge Subsystem (LESS); 12) 3D Reconstruction of Left WLE; 13) Left Wing Tile Table; 14) LESS Observations; 15) Left Hand Wing Debris Points to RCC 8/9 - Slumped Tile; 16) Reconstructed View of LC/P 9 tile with I/B Tile; 17) Reconstructed View of Lower C/P 9 Tile; 18) Carrier Panel 8 - Upper; 19) Left Hand Wing Debris Points to RCC 8/9 - Erosion and RCC with attach hole intact; 20) Erosion on Panel 8 Upper Outboard Rib; 21) RCC Panels 8 & 9 Erosion Features; 22) Slumping Source for Carrier Panel 9 Tile was Revealed; 23) Debris Indicated Highest Probability Initiation Site; 24) Left Hand Wing Debris Points to RCC 8/9- Metallic Deposits; 25) Relative Metallic Deposition on L/H Wing Materials; 26) Metallic Deposit Example, LH RCC 8; 27) High Level Questions; 28) Analysis Plan Challenges; 29) Analysis Techniques; 30) Analysis Approach; 31) RCC Panel 8 Erosion Features; 32) Radiographic Features; 33) Radiography WLE LH Panel 8; 34) LH RCC 8 Upper Apex; 35) LH RCC 8 - Deposit Feature: Thick Tear Shaped; 36) LH RCC 8 - Deposit Feature: Thick Globules; 37) LH RCC 8 - Deposit Feature: Spheroids; 38) LH RCC 8 - Deposit Feature: Uniform Deposit; 39) Significant Findings - Sampling All Other panels; 40) Proposed Breach Location and Plasma Flow; 41) Corroborating Information - RCC Panel Debris Locations; 42) Corroborating Information - LH OMS Pod Analysis; 43) Corroborating Information - Impact Testing; and 44) Overall Forensic Conclusions.

  7. Functional characteristics of spirilloxanthin and keto-bearing Analogues in light-harvesting LH2 complexes from Rhodobacter sphaeroides with a genetically modified carotenoid synthesis pathway.

    PubMed

    Niedzwiedzki, Dariusz M; Dilbeck, Preston L; Tang, Qun; Mothersole, David J; Martin, Elizabeth C; Bocian, David F; Holten, Dewey; Hunter, C Neil

    2015-01-01

    Light-harvesting 2 (LH2) complexes from a genetically modified strain of the purple photosynthetic bacterium Rhodobacter (Rba.) sphaeroides were studied using static and ultrafast optical methods and resonance Raman spectroscopy. Carotenoid synthesis in the Rba. sphaeroides strain was engineered to redirect carotenoid production away from spheroidene into the spirilloxanthin synthesis pathway. The strain assembles LH2 antennas with substantial amounts of spirilloxanthin (total double-bond conjugation length N=13) if grown anaerobically and of keto-bearing long-chain analogs [2-ketoanhydrorhodovibrin (N=13), 2-ketospirilloxanthin (N=14) and 2,2'-diketospirilloxanthin (N=15)] if grown semi-aerobically (with ratios that depend on growth conditions). We present the photophysical, electronic, and vibrational properties of these carotenoids, both isolated in organic media and assembled within LH2 complexes. Measurements of excited-state energy transfer to the array of excitonically coupled bacteriochlorophyll a molecules (B850) show that the mean lifetime of the first singlet excited state (S1) of the long-chain (N≥13) carotenoids does not change appreciably between organic media and the protein environment. In each case, the S1 state appears to lie lower in energy than that of B850. The energy-transfer yield is ~0.4 in LH2 (from the strain grown aerobically or semi-aerobically), which is less than half that achieved for LH2 that contains short-chain (N≤11) analogues. Collectively, the results suggest that the S1 excited state of the long-chain (N≥13) carotenoids participates little if at all in carotenoid-to-BChl a energy transfer, which occurs predominantly via the carotenoid S2 excited state in these antennas. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Changes of TSPO-mediated mitophagy signaling pathway in learned helplessness mice.

    PubMed

    Li, Dongmei; Zheng, Ji; Wang, Mingyang; Feng, Lu; Ren, Zhili; Liu, Yanyong; Yang, Nan; Zuo, Pingping

    2016-11-30

    Low response rate was witnessed with the present monoaminergic based antidepressants, urging a need for new therapeutic target identification. Accumulated evidences strongly suggest that mitochondrial deficit is implicated in major depression and 18kDa translocator protein (TSPO) plays an important role in regulating mitochondrial function. However the changes of TSPO and TSPO mediated mitophagy pathway in the depressive brain is unclear. In present study, a well validated animal model of depression, learned helplessness (LH), was employed to investigate the relevant changes. Significant behavioral changes were observed in the LH mice. Results showed that TSPO and other mitophagy related proteins, such as VDAC1, Pink1 and Beclin1 were significantly decreased by LH challenge. Moreover, KIFC2, relevant to the mitochondrial transport and Snap25, relevant to neurotransmitter vesicle release, were also obviously down-regulated in the LH mice, which further rendered supportive evidence for the existing mitochondrial dysfunction in LH mice. Present results demonstrated that LH induced depressive symptoms and affected TSPO-mediated mitophagy pathway, indicating a potential target candidate for depression treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. The ring structure and organization of light harvesting 2 complexes in a reconstituted lipid bilayer, resolved by atomic force microscopy.

    PubMed

    Stamouli, Amalia; Kafi, Sidig; Klein, Dionne C G; Oosterkamp, Tjerk H; Frenken, Joost W M; Cogdell, Richard J; Aartsma, Thijs J

    2003-04-01

    The main function of the transmembrane light-harvesting complexes in photosynthetic organisms is the absorption of a light quantum and its subsequent rapid transfer to a reaction center where a charge separation occurs. A combination of freeze-thaw and dialysis methods were used to reconstitute the detergent-solubilized Light Harvesting 2 complex (LH2) of the purple bacterium Rhodopseudomonas acidophila strain 10050 into preformed egg phosphatidylcholine liposomes, without the need for extra chemical agents. The LH2-containing liposomes opened up to a flat bilayer, which were imaged with tapping and contact mode atomic force microscopy under ambient and physiological conditions, respectively. The LH2 complexes were packed in quasicrystalline domains. The endoplasmic and periplasmic sides of the LH2 complexes could be distinguished by the difference in height of the protrusions from the lipid bilayer. The results indicate that the complexes entered in intact liposomes. In addition, it was observed that the most hydrophilic side, the periplasmic, enters first in the membrane. In contact mode the molecular structure of the periplasmic side of the transmembrane pigment-protein complex was observed. Using Föster's theory for describing the distance dependent energy transfer, we estimate the dipole strength for energy transfer between two neighboring LH2s, based on the architecture of the imaged unit cell.

  10. Incorporation of spheroidene and spheroidenone into light-harvesting complexes from purple sulfur bacteria.

    PubMed

    Ashikhmin, Aleksandr; Makhneva, Zoya; Bolshakov, Maksim; Moskalenko, Andrey

    2017-05-01

    Spheroidene and spheroidenone from the non-sulfur bacterium Rhodobacter (Rba.) sphaeroides were incorporated into diphenylamine (DPA) LH1-RC and LH2 complexes from sulfur bacteria Allochromatium (Alc.) minutissimum and Ectothiorhodospira (Ect.) haloalkaliphila in which carotenoid (Car) biosynthesis was inhibited by ~95%. A series of biochemical characteristics of the modified LH2 complexes was studied (electrophoretic mobility, absorption and CD spectra, Car composition, Car-to-BChl energy transfer and thermal stability). It was found that the electrophoretic mobility of the complexes with incorporated Cars did not change compared to that of the control and DPA-complexes, indicating the absence of any significant change in the structure of LH complexes upon DPA-treatment and subsequent incorporation of Cars. The analysis of fluorescence excitation spectra of the spheroidene-incorporated LH2 complex (LH2:sph) and the spheroidenone-incorporated LH2 complex (LH2:sph-ne) showed that spheroidene and spheroidenone exhibited relatively low efficiencies of energy transfer to BChl, when incorporated into the LH2 DPA-complexes from Alc. minutissimum and Ect. haloalkaliphila, although, they showed high efficiencies, being in their natural state in the LH2 complexes from Rba. sphaeroides. A significant increase in thermostability observed for the LH2:sph and LH2:sph-ne complexes with respect to the LH2 DPA-complexes indicated that the two incorporated Cars stabilized the structure of the LH2 complexes. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Structural Stability of Light-harvesting Protein LH2 Adsorbed on Mesoporous Silica Supports.

    PubMed

    Shibuya, Yuuta; Itoh, Tetsuji; Matsuura, Shun-ichi; Yamaguchi, Akira

    2015-01-01

    In the present study, we examined the reversible thermal deformation of the membrane protein light-harvesting complex LH2 adsorbed on mesoporous silica (MPS) supports. The LH2 complex from Thermochromatium tepidum cells was conjugated to MPS supports with a series of pore diameter (2.4 to 10.6 nm), and absorption spectra of the resulting LH2/MPS conjugates were observed over a temperature range of 273 - 313 K in order to examine the structure of the LH2 adsorbed on the MPS support. The experimental results confirmed that a slight ellipsoidal deformation of LH2 was induced by adsorption on the MPS supports. On the other hand, the structural stability of LH2 was not perturbed by the adsorption. Since the pore diameter of MPS support did not influence the structural stability of LH2, it could be considered that the spatial confinement of LH2 in size-matches pore did not improve the structural stability of LH2.

  12. The NMDA Receptor Subunit NR2b: Effects on LH Release and GnRH Gene Expression in Young and Middle-aged Female Rats, with Modulation by Estradiol

    PubMed Central

    Maffucci, Jacqueline A.; Walker, Deena M.; Ikegami, Aiko; Woller, Michael J.; Gore, Andrea C.

    2008-01-01

    The loss of reproductive capacity during aging involves changes in the neural regulation of the hypothalamic gonadotropin-releasing hormone (GnRH) neurons controlling reproduction. This neuronal circuitry includes glutamate receptors on GnRH neurons. Previously, we reported an increase in the expression of the NR2b subunit protein of the NMDA receptor on GnRH neurons in middle-aged compared to young female rats. Here, we examined the functional implications of the NR2b subunit on the onset of reproductive aging, using an NR2b-specific antagonist ifenprodil. Young (3–5 mos.) and middle-aged (10–13 mos.) female rats were ovariectomized (OVX), 17β-estradiol (E2) or vehicle (cholesterol) treated, and implanted with a jugular catheter. Serial blood sampling was undertaken every 10 minutes for 4 hours, with ifenprodil (10mg/kg) or vehicle injected (i.p.) after one hour of baseline sampling. The pulsatile release of pituitary LH and levels of GnRH mRNA in hypothalamus were quantified as indices of the reproductive axis. Our results showed effects of ifenprodil on both endpoints. In OVX rats given cholesterol, neither age nor ifenprodil had any effects on LH release. In E2-treated rats, aging was associated with significant decreases in pulsatile LH release. Additionally, ifenprodil stimulated parameters of pulsatile LH release in both young and middle-aged animals. Ifenprodil had few effects on GnRH mRNA; the only significant effect of ifenprodil was found in the middle-aged, cholesterol group. Together, these findings support a role for the NR2b subunit of the NMDAR in GnRH/LH regulation. Because most of these effects were exhibited on pituitary LH release in the absence of a concomitant change in GnRH gene expression, it is likely that NMDA receptors containing the NR2b subunit plays a role in GnRH-induced LH release, independent of de novo GnRH gene expression. PMID:18025808

  13. Neonatal handling and reproductive function in female rats.

    PubMed

    Gomes, C M; Raineki, C; Ramos de Paula, P; Severino, G S; Helena, C V V; Anselmo-Franci, J A; Franci, C R; Sanvitto, G L; Lucion, A B

    2005-02-01

    Neonatal handling induces anovulatory estrous cycles and decreases sexual receptivity in female rats. The synchronous secretion of hormones from the gonads (estradiol (E2) and progesterone (P)), pituitary (luteinizing (LH) and follicle-stimulating (FSH) hormones) and hypothalamus (LH-releasing hormone (LHRH)) are essential for the reproductive functions in female rats. The present study aimed to describe the plasma levels of E2 and P throughout the estrous cycle and LH, FSH and prolactin (PRL) in the afternoon of the proestrus, and the LHRH content in the medial preoptic area (MPOA), median eminence (ME) and medial septal area (MSA) in the proestrus, in the neonatal handled rats. Wistar pup rats were handled for 1 min during the first 10 days after delivery (neonatal handled group) or left undisturbed (nonhandled group). When they reached adulthood, blood samples were collected through a jugular cannula and the MPOA, ME and MSA were microdissected. Plasma levels of the hormones and the content of LHRH were determined by RIA. The number of oocytes counted in the morning of the estrus day in the handled rats was significantly lower than in the nonhandled ones. Neonatal handling reduces E2 levels only on the proestrus day while P levels decreased in metestrus and estrus. Handled females also showed reduced plasma levels of LH, FSH and PRL in the afternoon of the proestrus. The LHRH content in the MPOA was significantly higher than in the nonhandled group. The reduced secretion of E2, LH, FSH and LHRH on the proestrus day may explain the anovulatory estrous cycle in neonatal handled rats. The reduced secretion of PRL in the proestrus may be related to the decreased sexual receptiveness in handled females. In conclusion, early-life environmental stimulation can induce long-lasting effects on the hypothalamus-pituitary-gonad axis.

  14. Selective binding of carotenoids with a shorter conjugated chain to the LH2 antenna complex and those with a longer conjugated chain to the reaction center from Rubrivivax gelatinosus.

    PubMed

    Kakitani, Yoshinori; Fujii, Ritsuko; Hayakawa, Yoshihiro; Kurahashi, Masahiro; Koyama, Yasushi; Harada, Jiro; Shimada, Keizo

    2007-06-19

    Rubrivivax gelatinosus having both the spheroidene and spirilloxanthin biosynthetic pathways produces carotenoids (Cars) with a variety of conjugated chains, which consist of different numbers of conjugated double bonds (n), including the C=C (m) and C=O (o) bonds. When grown under anaerobic conditions, the wild type produces Cars for which n = m = 9-13, whereas under semiaerobic conditions, it additionally produces Cars for which n = m + o = 10 + 1, 13 + 1, and 13 + 2. On the other hand, a mutant, in which the latter pathway is genetically blocked, produces only Cars for which n = 9 and 10 under anaerobic conditions and n = 9, 10, and 10 + 1 under semianaerobic conditions. Those Cars that were extracted from the LH2 complex (LH2) and the reaction center (RC), isolated from the wild-type and the mutant Rvi. gelatinosus, were analyzed by HPLC, and their structures were determined by mass spectrometry and 1H NMR spectroscopy. The selective binding of Cars to those pigment-protein complexes has been characterized as follows. (1) Cars with a shorter conjugated chain are selectively bound to LH2 whereas Cars with a longer conjugated chain to the RC. (2) Shorter chain Cars with a hydroxyl group are bound to LH2 almost exclusively. This rule holds either in the absence or in the presence of the keto group. The natural selection of shorter chain Cars by LH2 and longer chain Cars by the RC is discussed, on the basis of the results now available, in relation to the light-harvesting and photoprotective functions of Cars.

  15. Architecture of GnRH-Gonadotrope-Vasculature Reveals a Dual Mode of Gonadotropin Regulation in Fish.

    PubMed

    Golan, Matan; Zelinger, Einat; Zohar, Yonathan; Levavi-Sivan, Berta

    2015-11-01

    The function and components of the hypothalamic-pituitary axis are conserved among vertebrates; however, in fish, a neuroglandular mode of delivery (direct contact between axons and endocrine cells) was considered dominant, whereas in tetrapods hypothalamic signals are relayed to their targets via the hypophysial portal blood system (neurovascular delivery mode). By using a transgenic zebrafish model we studied the functional and anatomical aspects of gonadotrope regulation thus revisiting the existing model. FSH cells were found to be situated close to the vasculature whereas the compact organization of LH cells prevented direct contact of all cells with the circulation. GnRH3 fibers formed multiple boutons upon reaching the pituitary, but most of these structures were located in the neurohypophysis rather than adjacent to gonadotropes. A close association was observed between FSH cells and GnRH3 boutons, but only a fifth of the LH cells were in direct contact with GnRH3 axons, suggesting that FSH cells are more directly regulated than LH cells. GnRH3 fibers closely followed the vasculature in the neurohypophysis and formed numerous boutons along these tracts. These vessels were found to be permeable to relatively large molecules, suggesting the uptake of GnRH3 peptides. Our findings have important implications regarding the differential regulation of LH and FSH and contradict the accepted notion that fish pituitary cells are mostly regulated directly by hypothalamic fibers. Instead, we provide evidence that zebrafish apply a dual mode of gonadotrope regulation by GnRH3 that combines both neuroglandular and neurovascular components.

  16. Carotenoid radical cation formation in LH2 of purple bacteria: a quantum chemical study.

    PubMed

    Wormit, Michael; Dreuw, Andreas

    2006-11-30

    In LH2 complexes of Rhodobacter sphaeroides the formation of a carotenoid radical cation has recently been observed upon photoexcitation of the carotenoid S2 state. To shed more light onto the yet unknown molecular mechanism leading to carotenoid radical formation in LH2, the interactions between carotenoid and bacteriochlorophyll in LH2 are investigated by means of quantum chemical calculations for three different carotenoids--neurosporene, spheroidene, and spheroidenone--using time-dependent density functional theory. Crossings of the calculated potential energy curve of the electron transfer state with the bacteriochlorophyll Qx state and the carotenoid S1 and S2 states occur along an intermolecular distance coordinate for neurosporene and spheroidene, but for spheroidenone no crossing of the electron transfer state with the carotenoid S1 state could be found. By comparison with recent experiments where no formation of a spheroidenone radical cation has been observed, a molecular mechanism for carotenoid radical cation formation is proposed in which it is formed via a vibrationally excited carotenoid S1 or S*state. Arguments are given why the formation of the carotenoid radical cation does not proceed via the Qx, S2, or higher excited electron transfer states.

  17. GUI for Computational Simulation of a Propellant Mixer

    NASA Technical Reports Server (NTRS)

    Figueroa, Fernando; Richter, Hanz; Barbieri, Enrique; Granger, Jamie

    2005-01-01

    Control Panel is a computer program that generates a graphical user interface (GUI) for computational simulation of a rocket-test-stand propellant mixer in which gaseous hydrogen (GH2) is injected into flowing liquid hydrogen (LH2) to obtain a combined flow having desired thermodynamic properties. The GUI is used in conjunction with software that models the mixer as a system having three inputs (the positions of the GH2 and LH2 inlet valves and an outlet valve) and three outputs (the pressure inside the mixer and the outlet flow temperature and flow rate). The user can specify valve characteristics and thermodynamic properties of the input fluids via userfriendly dialog boxes. The user can enter temporally varying input values or temporally varying desired output values. The GUI provides (1) a set-point calculator function for determining fixed valve positions that yield desired output values and (2) simulation functions that predict the response of the mixer to variations in the properties of the LH2 and GH2 and manual- or feedback-control variations in valve positions. The GUI enables scheduling of a sequence of operations that includes switching from manual to feedback control when a certain event occurs.

  18. Commercial radioimmunoassay for beta subunit of human chorionic gonadotropin: falsely positive determinations due to elevated serum luteinizing hormone

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fowler, J.E. Jr.; Platoff, G.E.; Kubrock, C.A.

    1982-01-01

    Among 17 men who had received seemingly curative treatment for unilateral non-seminomatous germ cell tumors for the testis and who had consistently normal serum human chorionic gonadotropin (HCG) levels at a reference laboratory, 7 (41%) had at least one falsely positive commercial serum HCG determination. To investigate the cause of these falsely positive determinations the authors measured the cross reactivity of luteinizing hormone (LH) and follicle stimulating hormone (FSH) standards in the commercial HCG assay, and studied the relationships between commercial HCG levels and serum LH levels, serum FSH levels and gonadal status in men with and without normal gonadalmore » function. The falsely positive HCG determinations appeared to be due to elevated serum LH levels and cross reactivity of LH in the commercial HCG assay because: 1) there was substantial cross reactivity of the LH standards in the commercial assay, 2) the serum LH was elevated in four of six men with solitary testes, 3) there was a striking correlation between elevated serum LH levels and falsely elevated commercial HCG levels in ten men with solitary or absent testes, and 4) there were no falsely positive HCG determinations in 13 normal men but there were falsely positive HCG determinations in seven of ten anorchid men.« less

  19. Parabrachial and hypothalamic interaction in sodium appetite

    PubMed Central

    Dayawansa, S.; Peckins, S.; Ruch, S.

    2011-01-01

    Rats with bilateral lesions of the lateral hypothalamus (LH) fail to exhibit sodium appetite. Lesions of the parabrachial nuclei (PBN) also block salt appetite. The PBN projection to the LH is largely ipsilateral. If these deficits are functionally dependent, damaging the PBN on one side and the LH on the other should also block Na appetite. First, bilateral ibotenic acid lesions of the LH were needed because the electrolytic damage used previously destroyed both cells and axons. The ibotenic LH lesions produced substantial weight loss and eliminated Na appetite. Controls with ipsilateral PBN and LH lesions gained weight and displayed robust sodium appetite. The rats with asymmetric PBN-LH lesions also gained weight, but after sodium depletion consistently failed to increase intake of 0.5 M NaCl. These results dissociate loss of sodium appetite from the classic weight loss after LH damage and prove that Na appetite requires communication between neurons in the LH and the PBN. PMID:21270347

  20. Protein Structural Deformation Induced Lifetime Shortening of Photosynthetic Bacteria Light-Harvesting Complex LH2 Excited State

    PubMed Central

    Chen, Xing-Hai; Zhang, Lei; Weng, Yu-Xiang; Du, Lu-Chao; Ye, Man-Ping; Yang, Guo-Zhen; Fujii, Ritsuko; Rondonuwu, Ferdy S.; Koyama, Yasushi; Wu, Yi-Shi; Zhang, J. P.

    2005-01-01

    Photosynthetic bacterial light-harvesting antenna complex LH2 was immobilized on the surface of TiO2 nanoparticles in the colloidal solution. The LH2/TiO2 assembly was investigated by the time-resolved spectroscopic methods. The excited-state lifetimes for carotenoid-containing and carotenoidless LH2 have been measured, showing a decrease in the excited-state lifetime of B850 when LH2 was immobilized on TiO2. The possibility that the decrease of the LH2 excited-state lifetime being caused by an interfacial electron transfer reaction between B850 and the TiO2 nanoparticle was precluded experimentally. We proposed that the observed change in the photophysical properties of LH2 when assembled onto TiO2 nanoparticles is arising from the interfacial-interaction-induced structural deformation of the LH2 complex deviating from an ellipse of less eccentric to a more eccentric ellipse, and the observed phenomenon can be accounted by an elliptical exciton model. Experiment by using photoinactive SiO2 nanoparticle in place of TiO2 and core complex LH1 instead of LH2 provide further evidence to the proposed mechanism. PMID:15821161

  1. Protein structural deformation induced lifetime shortening of photosynthetic bacteria light-harvesting complex LH2 excited state.

    PubMed

    Chen, Xing-Hai; Zhang, Lei; Weng, Yu-Xiang; Du, Lu-Chao; Ye, Man-Ping; Yang, Guo-Zhen; Fujii, Ritsuko; Rondonuwu, Ferdy S; Koyama, Yasushi; Wu, Yi-Shi; Zhang, J P

    2005-06-01

    Photosynthetic bacterial light-harvesting antenna complex LH2 was immobilized on the surface of TiO(2) nanoparticles in the colloidal solution. The LH2/TiO(2) assembly was investigated by the time-resolved spectroscopic methods. The excited-state lifetimes for carotenoid-containing and carotenoidless LH2 have been measured, showing a decrease in the excited-state lifetime of B850 when LH2 was immobilized on TiO(2). The possibility that the decrease of the LH2 excited-state lifetime being caused by an interfacial electron transfer reaction between B850 and the TiO(2) nanoparticle was precluded experimentally. We proposed that the observed change in the photophysical properties of LH2 when assembled onto TiO(2) nanoparticles is arising from the interfacial-interaction-induced structural deformation of the LH2 complex deviating from an ellipse of less eccentric to a more eccentric ellipse, and the observed phenomenon can be accounted by an elliptical exciton model. Experiment by using photoinactive SiO(2) nanoparticle in place of TiO(2) and core complex LH1 instead of LH2 provide further evidence to the proposed mechanism.

  2. Carotenoid-to-bacteriochlorophyll energy transfer through vibronic coupling in LH2 from Phaeosprillum molischianum.

    PubMed

    Thyrhaug, Erling; Lincoln, Craig N; Branchi, Federico; Cerullo, Giulio; Perlík, Václav; Šanda, František; Lokstein, Heiko; Hauer, Jürgen

    2018-03-01

    The peripheral light-harvesting antenna complex (LH2) of purple photosynthetic bacteria is an ideal testing ground for models of structure-function relationships due to its well-determined molecular structure and ultrafast energy deactivation. It has been the target for numerous studies in both theory and ultrafast spectroscopy; nevertheless, certain aspects of the convoluted relaxation network of LH2 lack a satisfactory explanation by conventional theories. For example, the initial carotenoid-to-bacteriochlorophyll energy transfer step necessary on visible light excitation was long considered to follow the Förster mechanism, even though transfer times as short as 40 femtoseconds (fs) have been observed. Such transfer times are hard to accommodate by Förster theory, as the moderate coupling strengths found in LH2 suggest much slower transfer within this framework. In this study, we investigate LH2 from Phaeospirillum (Ph.) molischianum in two types of transient absorption experiments-with narrowband pump and white-light probe resulting in 100 fs time resolution, and with degenerate broadband 10 fs pump and probe pulses. With regard to the split Q x band in this system, we show that vibronically mediated transfer explains both the ultrafast carotenoid-to-B850 transfer, and the almost complete lack of transfer to B800. These results are beyond Förster theory, which predicts an almost equal partition between the two channels.

  3. Monoclonal antibodies against loggerhead sea turtle, Caretta caretta, IgY isoforms reveal differential contributions to antibody titers and relatedness among other sea turtles.

    PubMed

    Rodgers, Maria L; Rice, Charles D

    2018-05-19

    Serum from loggerhead sea turtles, Caretta caretta, was collected from the southeast Atlantic Ocean during routine summer monitoring studies in 2017. Serum immunoglobulin IgY was purified and used to develop IgY isoform-specific monoclonal antibodies (mAb). mAb LH12 was developed against the 66 kDa heavy chain of IgY, mAb LH1 was developed against the truncated heavy chain of approximately 37 kDA, and mAb LH9 was developed against the 23 kDa light chains. mAb LH9 reacts with the light chains of all sea turtles, mAb LH12 reacts with the long heavy chain of all sea turtles within the family Cheloniidae, and mAb LH1 reacts with the truncated form of IgY in both olive and Kemp's ridley turtles. Circulating IgY antibodies against three different marine bacterial pathogens were determined in 16 loggerhead samples using these mAbs. mAb LH12 detects higher titers than mAb LH1, and mAb LH9 detects the highest titers. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Single-Molecule Spectroscopy Unmasks the Lowest Exciton State of the B850 Assembly in LH2 from Rps. acidophila

    PubMed Central

    Kunz, Ralf; Timpmann, Kõu; Southall, June; Cogdell, Richard J.; Freiberg, Arvi; Köhler, Jürgen

    2014-01-01

    We have recorded fluorescence-excitation and emission spectra from single LH2 complexes from Rhodopseudomonas (Rps.) acidophila. Both types of spectra show strong temporal spectral fluctuations that can be visualized as spectral diffusion plots. Comparison of the excitation and emission spectra reveals that for most of the complexes the lowest exciton transition is not observable in the excitation spectra due to the cutoff of the detection filter characteristics. However, from the spectral diffusion plots we have the full spectral and temporal information at hand and can select those complexes for which the excitation spectra are complete. Correlating the red most spectral feature of the excitation spectrum with the blue most spectral feature of the emission spectrum allows an unambiguous assignment of the lowest exciton state. Hence, application of fluorescence-excitation and emission spectroscopy on the same individual LH2 complex allows us to decipher spectral subtleties that are usually hidden in traditional ensemble spectroscopy. PMID:24806933

  5. A preclinical evaluation of an autologous living hyaline-like cartilaginous graft for articular cartilage repair: a pilot study.

    PubMed

    Peck, Yvonne; He, Pengfei; Chilla, Geetha Soujanya V N; Poh, Chueh Loo; Wang, Dong-An

    2015-11-09

    In this pilot study, an autologous synthetic scaffold-free construct with hyaline quality, termed living hyaline cartilaginous graft (LhCG), was applied for treating cartilage lesions. Implantation of autologous LhCG was done at load-bearing regions of the knees in skeletally mature mini-pigs for 6 months. Over the course of this study, significant radiographical improvement in LhCG treated sites was observed via magnetic resonance imaging. Furthermore, macroscopic repair was effected by LhCG at endpoint. Microscopic inspection revealed that LhCG engraftment restored cartilage thickness, promoted integration with surrounding native cartilage, produced abundant cartilage-specific matrix molecules, and re-established an intact superficial tangential zone. Importantly, the repair efficacy of LhCG was quantitatively shown to be comparable to native, unaffected cartilage in terms of biochemical composition and biomechanical properties. There were no complications related to the donor site of cartilage biopsy. Collectively, these results imply that LhCG engraftment may be a viable approach for articular cartilage repair.

  6. A preclinical evaluation of an autologous living hyaline-like cartilaginous graft for articular cartilage repair: a pilot study

    PubMed Central

    Peck, Yvonne; He, Pengfei; Chilla, Geetha Soujanya V. N.; Poh, Chueh Loo; Wang, Dong-An

    2015-01-01

    In this pilot study, an autologous synthetic scaffold-free construct with hyaline quality, termed living hyaline cartilaginous graft (LhCG), was applied for treating cartilage lesions. Implantation of autologous LhCG was done at load-bearing regions of the knees in skeletally mature mini-pigs for 6 months. Over the course of this study, significant radiographical improvement in LhCG treated sites was observed via magnetic resonance imaging. Furthermore, macroscopic repair was effected by LhCG at endpoint. Microscopic inspection revealed that LhCG engraftment restored cartilage thickness, promoted integration with surrounding native cartilage, produced abundant cartilage-specific matrix molecules, and re-established an intact superficial tangential zone. Importantly, the repair efficacy of LhCG was quantitatively shown to be comparable to native, unaffected cartilage in terms of biochemical composition and biomechanical properties. There were no complications related to the donor site of cartilage biopsy. Collectively, these results imply that LhCG engraftment may be a viable approach for articular cartilage repair. PMID:26549401

  7. Fox-2 protein regulates the alternative splicing of scleroderma-associated lysyl hydroxylase 2 messenger RNA.

    PubMed

    Seth, Puneet; Yeowell, Heather N

    2010-04-01

    Scleroderma (systemic sclerosis [SSc]) is a complex connective tissue disorder characterized by hardening and thickening of the skin. One hallmark of scleroderma is excessive accumulation of collagen accompanied by increased levels of pyridinoline collagen crosslinks derived from hydroxylysine residues in the collagen telopeptide domains. Lysyl hydroxylase 2 (LH2), an important alternatively spliced enzyme in collagen biosynthesis, acts as a collagen telopeptide hydroxylase. Changes in the pattern of LH2 alternative splicing, favoring increased inclusion of the alternatively spliced LH2 exon 13A, thereby increasing the levels of the long transcript of LH2 (LH2[long]), are linked to scleroderma disease. This study was undertaken to examine the role played by RNA binding protein Fox-2 in regulating exon 13A inclusion, which leads to the generation of scleroderma-associated LH2(long) messenger RNA (mRNA). Phylogenetic sequence analysis of introns flanking exon 13A was performed. A tetracycline-inducible system in T-Rex 293 cells was used to induce Fox-2 protein, and endogenous LH2(long) mRNA was determined by reverse transcriptase-polymerase chain reaction. An LH2 minigene was designed, validated, and used in Fox-2 overexpression and mutagenesis experiments. Knockdown of Fox-2 was performed in mouse embryonic fibroblasts and in fibroblasts from SSc patients. Overexpression of Fox-2 enhanced the inclusion of exon 13A and increased the generation of LH2(long) mRNA, whereas knockdown of Fox-2 decreased LH2(long) transcripts. Mutational analysis of an LH2 minigene demonstrated that 2 of the 4 Fox binding motifs flanking LH2 exon 13A are required for inclusion of exon 13A. In early passage fibroblasts derived from patients with scleroderma, the knockdown of Fox-2 protein significantly decreased the endogenous levels of LH2(long) mRNA. Our findings indicate that Fox-2 plays an integral role in the regulation of LH2 splicing. Knockdown of Fox-2 and other methods to decrease the levels of fibrosis-associated LH2(long) mRNA in primary scleroderma cells may suggest a novel approach to strategies directed against scleroderma.

  8. Activity of the hypothalamo-pituitary axis and testicular development in prepubertal ram lambs with induced hypothyroidism or hyperthyroidism.

    PubMed

    Chandrasekhar, Y; D'Occhio, M J; Holland, M K; Setchell, B P

    1985-10-01

    Prepubertal (16 weeks old) ram lambs were used to investigate the effects of hyperthyroidism and hypothyroidism on development of reproductive endocrine function. Over a period of 8 weeks, ram lambs were made hypothyroid (serum T4 less than or equal to 3 ng/ml compared with controls congruent to 30 ng/ml) by daily oral administration of methyl thiouracil or hyperthyroid (serum T4 congruent to 135 ng/ml) by daily sc injection of T4. Hyperthyroidism was associated with decreases in LH pulse frequency (2.25 +/- 0.75/12 h compared with controls 5.75 +/- 0.48/12 h), basal LH, and mean LH concentrations, together with arrested testicular growth and aspermatogenesis. Hypothyroid rams showed normal pubertal development. After iv injection of LHRH, hyperthyroid ram lambs showed similar LH responses to control and hypothyroid rams. Basal testosterone production (5.6 +/- 1.0 ng/min) and plasma testosterone concentrations after human CG (2.0 +/- 0.7 ng/ml) in hyperthyroid rams were significantly lower than in controls (67.5 +/- 24.0 ng/min and 5.2 +/- 1.0 ng/ml, respectively). It is concluded that retarded testicular development in hyperthyroid ram lambs results from changes in hypothalamo-pituitary activity manifested in a decreased LH pulse frequency.

  9. Laser vocal cordectomy fails to effectively reduce respiratory noise in horses with laryngeal hemiplegia.

    PubMed

    Brown, Jennifer A; Derksen, Frederik J; Stick, John A; Hartmann, William M; Robinson, N Edward

    2005-01-01

    To report the effect of unilateral laser vocal cordectomy on respiratory noise and airway function in horses with experimentally induced laryngeal hemiplegia (LH). Experimental study. Six Standardbred horses without upper airway abnormalities at rest or during high-speed treadmill exercise. Respiratory sounds and inspiratory trans-upper airway pressure (P(Ui)) were measured before (baseline) and 14 days after induction of LH by left recurrent laryngeal neurectomy, and again 30, 60, 90, and 120 days after endoscopically assisted laser cordectomy of the left vocal cord. Data were collected with the horses exercising on a treadmill at a speed producing maximum heart rate (HR(max)). In horses exercising at HR(max), induction of LH caused a significant increase in P(Ui), sound level (SL), and the sound intensity of formant 2 (F(2)) and 3 (F(3)). The sound intensity of formant 1 (F(1)) was unaffected by induction of LH. Laser vocal cordectomy had no effect on SL, or on the sound intensity of F(1) and F(3). At 30, 60, 90, and 120 days after surgery, P(Ui) and the sound intensity of F(2) were significantly reduced, but these variables remained significantly different from baseline values. Unilateral laser vocal cordectomy did not effectively improve upper airway noise in horses with LH. The procedure decreased upper airway obstruction to the same degree as bilateral ventriculocordectomy. Currently, laser vocal cordectomy cannot be recommended for the treatment of upper airway noise in horses with LH.

  10. Women with oligo-/amenorrhoea and polycystic ovaries have identical responses to GnRH stimulation regardless of their androgen status: comparison of the Rotterdam and Androgen Excess Society diagnostic criteria.

    PubMed

    Lewandowski, Krzysztof C; Cajdler-Luba, Agata; Bieńkiewicz, Małgorzata; Lewiński, Andrzej

    2011-01-01

    As increased frequency of gonadotrophin-releasing hormone (GnRH) pulses is characteristic for polycystic ovary syndrome (PCOS), we assessed gonadotrophin response to GnRH in women with PCOS with normal and raised androgens and in regularly menstruating controls. The study involved 155 subjects: PCOS, n=121, age (mean±SD) 24.8±5.4 yrs, BMI 24.5±6.0 kg/m2, all with oligo-/amenorrhoea and PCO morphology, and 34 controls. Gonadotrophins were measured in early follicular phase after GnRH stimulation (0, 30 and 60 minutes). Fifty four (41.9%) women with PCOS had androgens (testosterone, androstendione, dihydroepiandrosterone sulphate) within the reference range, and would fulfil the "Rotterdam", but not the Androgen Excess Society PCOS criteria. Baseline and stimulated LH concentrations were higher in PCOS (9.09±5.56 vs 4.83±1.71 IU/l, 35.48±31.4 vs 16.30±6.68 IU/l, 33.86±31.8 vs 13.45±5.2 IU/l, at 0, 30 and 60 min post GnRH, respectively, p<0.0001). An LH/FSH ratio in PCOS increased further after GnRH stimulation. ROC analysis revealed that LH30min/FSH30min >2.11 or LH60min/FSH60min >1.72 had 78.3% and 87.5% sensitivity and 81.7% and 81.3% specificity for diagnosis of PCOS. Both baseline and GnRH-stimulated LH and FSH concentrations were similar in women with PCOS and raised androgens and with androgens within the reference range (p=0.71 and p=0.20 for LH and FSH, respectively). Regardless of their androgen status, women with PCO morphology and oligo-/amenorrhoea have higher baseline and GnRH-stimulated LH concentrations and higher GnRH-stimulated LH/FSH ratio than controls, suggestive of similar underlying mechanism accounting for menstrual irregularities. These observations support validity of PCOS diagnostic criteria based on the Rotterdam consensus.

  11. On the role of precipitation latent heating in modulating the strength and width of the Hadley circulation

    NASA Astrophysics Data System (ADS)

    Mathew, Sneha Susan; Kumar, Karanam Kishore

    2018-05-01

    The latent heat released in the clouds over the tropics plays a vital role in driving the Hadley circulation (HC). The present study discusses the influence of latent heating (LH) on the HC parameters viz., centre, strength and total width by using precipitation LH profiles derived from the space-borne observations of the Precipitation Radar (PR) onboard Tropical Rain Measuring Mission (TRMM) and meridional stream function (MSF) derived from ECMWF-Interim reanalysis. The latitude of peak latent heating, width of the latent heating distribution and the total LH released within the ascending limb of the HC are estimated and their influence on the HC centre, strength and width is quantified, for the first time. The present results show that the latitude of peak LH significantly influences the position of the HC centre with correlation coefficient of 0.90. This high correlation between these two quantities seems to be due to their co-variability with the apparent motion of the Sun across the latitudes. The intensity of the HC in the NH as well as SH shows high correlation with the latitude of peak LH with coefficients - 0.85 and - 0.78, respectively. These results indicate that farther the latitude of peak LH from the equator in the summer hemisphere, stronger is the HC intensity in the winter hemisphere. The present analysis also reveals that the total LH released within the ascending limb of HC substantially influence the total width of the HC, with correlation coefficient 0.52, as compared to the other two LH parameters. This observation can be attributed to the fact that the HC is sensitive to the latent heat release in the mid-tropospheric levels in the tropics. An attempt is also made to investigate the degree of variability of these parameters after deseasonalization and results are discussed in the light of present understanding. The significance of the present study lies in providing the observational evidence for the influence of latent heating on the HC strength/width variability, quantitatively, for the first time using TRMM observations of precipitation latent heating.

  12. Acoustic analyses of thyroidectomy-related changes in vowel phonation.

    PubMed

    Solomon, Nancy Pearl; Awan, Shaheen N; Helou, Leah B; Stojadinovic, Alexander

    2012-11-01

    Changes in vocal function that can occur after thyroidectomy were tracked with acoustic analyses of sustained vowel productions. The purpose was to determine which time-based or spectral/cepstral-based measures of two vowels were able to detect voice changes over time in patients undergoing thyroidectomy. Prospective, longitudinal, and observational clinical trial. Voice samples of sustained /ɑ/ and /i/ recorded from 70 adults before and approximately 2 weeks, 3 months, and 6 months after thyroid surgery were analyzed for jitter, shimmer, harmonic-to-noise ratio (HNR), cepstral peak prominence (CPP), low-to-high ratio of spectral energy (L/H ratio), and the standard deviations of CPP and L/H ratio. Three trained listeners rated vowel and sentence productions for the four data collection sessions for each participant. For analysis purposes, participants were categorized post hoc according to voice outcome (VO) at their first postthyroidectomy assessment session. Shimmer, HNR, and CPP differed significantly across sessions; follow-up analyses revealed the strongest effect for CPP. CPP for /ɑ/ and /i/ differed significantly between groups of participants with normal versus negative (adverse) VO and between the pre- and 2-week postthyroidectomy sessions for the negative VO group. HNR, CPP, and L/H ratio differed across vowels, but both /ɑ/ and /i/ were similarly effective in tracking voice changes over time and differentiating VO groups. This study indicated that shimmer, HNR, and CPP determined from vowel productions can be used to track changes in voice over time as patients undergo and subsequently recover from thyroid surgery, with CPP being the strongest variable for this purpose. Evidence did not clearly reveal whether acoustic voice evaluations should include both /ɑ/ and /i/ vowels, but they should specify which vowel is used to allow for comparisons across studies and multiple clinical assessments. Copyright © 2012 The Voice Foundation. All rights reserved.

  13. Fluorescence-excitation and emission spectra from LH2 antenna complexes of Rhodopseudomonas acidophila as a function of the sample preparation conditions.

    PubMed

    Kunz, Ralf; Timpmann, Kõu; Southall, June; Cogdell, Richard J; Köhler, Jürgen; Freiberg, Arvi

    2013-10-10

    The high sensitivity of optical spectra of pigment-protein complexes to temperature and pressure is well known. In the present study, we have demonstrated the significant influence of the environments commonly used in bulk and single-molecule spectroscopic studies at low temperatures on the LH2 photosynthetic antenna complex from Rhodopseudomonas acidophila. A transfer of this LH2 complex from a bulk-buffer solution into a spin-coated polymer film results in a 189 cm(-1) blue shift of the B850 excitonic absorption band at 5 K. Within the molecular exciton model, the origin of this shift could be disentangled into three parts, namely to an increase of the local site energies, a contraction of the exciton band, and a decrease of the displacement energy.

  14. Does the endometrial gene expression of fertile women vary within and between cycles?

    PubMed

    Evans, Gloria E; Phillipson, Gregory T M; Sykes, Peter H; McNoe, Les A; Print, Cristin G; Evans, John J

    2018-01-23

    Does gene expression of putative endometrial implantation markers vary in expression between menstrual cycles? In fertile women the expression of certain genes exhibits a pattern of stable regulation.which is not affected even when sampled twice in one cycle. Successful implantation occurs in a minority of IVF embryo transfers. In contrast to knowledge regarding the ovulatory process, there is a sparse understanding of endometrial genes critical to implantation. This lack of knowledge hinders progress in this field. Endometrial pipelle samples were collected based on blood endocrinological markers at 2 and 7 days post initial LH surge. Five samples were collected over four cycles where the interval between collections ranged from sequential months to three years. Six fertile women attending an IVF clinic for male factor infertility, had samples collected. Global gene expression profiles were obtained from laser-microdissected, endometrial glands and stroma. Nineteen potential proliferation, cytokine and adhesion markers based on previous validated reports were studied. There was a significant modification between LH+2 and LH+7 of expression for 23 genes-11 in 8 in glands and stroma, 4 in stroma only and 3 in glands only suggesting stable, controlled regulation. Nevertheless, genes exhibited individual characteristics, e.g MKI67 exhibited lower expression at LH+7 than LH+2 and CCL4 higher, whereas TRO expressed limited difference in both cell types. Stability between cycles was demonstrated for gene expression at both LH+2-more than 60% of genes had <25% variation and at LH+7-60% had <30% variation. Further, effects of prior collection of an LH+2 sample on gene expression at LH+7 were not detected. The range of mRNA expression suggested that a clinical/diagnostic sample at LH+2 and LH+7 is likely to be a better index of endometrial function than a single sample. The possibility of redundancy suggests a panel would be more informative than a single marker. Raw and normalized microarray data have been deposited with the EMBL's European Genome-Phenome Archive for collaborative analysis, reference ega-box-815 (Lappalainen I, Almeida-King J, Kumanduri V, Senf A, Spalding JD, Ur-Rehman S, Saunders G, Kandasamy J, Caccamo M, Leinonen R et al. The European Genome-phenome Archive of human data consented for biomedical research. Nat Genet 2015;47:692-695.) [https://www.ebi.ac.uk/ega/home]. This type of research has difficulties of recruitment of fertile women for multiple blood testing and repeat endometrial biopsies. Therefore, these data had decreased statistical power due to the overall participant numbers. However, the inclusion of four cycles for each participant permitted the aim of obtaining information on intercycle and intracycle variability to be achieved. Our results support the feasibility of a clinical means of identification of a functional receptive endometrium. The robustness of data from individual women suggests that samples from one cycle can generally be applied to subsequent cycles. Funding was granted from the Tertiary Education Commission of New Zealand, Contract I.D.:UOOX06007. There are no competing interests. © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  15. Seasonal effects of irrigation on land-atmosphere latent heat, sensible heat, and carbon fluxes in semiarid basin

    NASA Astrophysics Data System (ADS)

    Zeng, Yujin; Xie, Zhenghui; Liu, Shuang

    2017-02-01

    Irrigation, which constitutes ˜ 70 % of the total amount of freshwater consumed by the human population, is significantly impacting land-atmosphere fluxes. In this study, using the improved Community Land Model version 4.5 (CLM4.5) with an active crop model, two high-resolution (˜ 1 km) simulations investigating the effects of irrigation on latent heat (LH), sensible heat (SH), and carbon fluxes (or net ecosystem exchange, NEE) from land to atmosphere in the Heihe River basin in northwestern China were conducted using a high-quality irrigation dataset compiled from 1981 to 2013. The model output and measurements from remote sensing demonstrated the capacity of the developed models to reproduce ecological and hydrological processes. The results revealed that the effects of irrigation on LH and SH are strongest during summer, with a LH increase of ˜ 100 W m-2 and a SH decrease of ˜ 60 W m-2 over intensely irrigated areas. However, the reactions are much weaker during spring and autumn when there is much less irrigation. When the irrigation rate is below 5 mm day-1, the LH generally increases, whereas the SH decreases with growing irrigation rates. However, when the irrigation threshold is in excess of 5 mm day-1, there is no accrued effect of irrigation on the LH and SH. Irrigation produces opposite effects to the NEE during spring and summer. During the spring, irrigation yields more discharged carbon from the land to the atmosphere, increasing the NEE value by 0.4-0.8 gC m-2 day-1, while the summer irrigation favors crop fixing of carbon from atmospheric CO2, decreasing the NEE value by ˜ 0.8 gC m-2 day-1. The repercussions of irrigation on land-atmosphere fluxes are not solely linked to the irrigation amount, and other parameters (especially the temperature) also control the effects of irrigation on LH, SH, and NEE.

  16. Synthesis and iron sequestration equilibria of novel exocyclic 3-hydroxy-2-pyridinone donor group siderophore mimics.

    PubMed

    Harrington, James M; Chittamuru, Sumathi; Dhungana, Suraj; Jacobs, Hollie K; Gopalan, Aravamudan S; Crumbliss, Alvin L

    2010-09-20

    The synthesis of a novel class of exocyclic bis- and tris-3,2-hydroxypyridinone (HOPO) chelators built on N(2) and N(3) aza-macrocyclic scaffolds and the thermodynamic solution characterization of their complexes with Fe(III) are described. The chelators for this study were prepared by reaction of either piperazine or N,N',N''-1,4,7-triazacyclononane with a novel electrophilic HOPO iminium salt in good yields. Subsequent removal of the benzyl protecting groups using HBr/acetic acid gave bis-HOPO chelators N(2)(etLH)(2) and N(2)(prLH)(2), and tris-HOPO chelator N(3)(etLH)(3) in excellent yields. Solution thermodynamic characterization of their complexes with Fe(III) was accomplished using spectrophotometric, potentiometric, and electrospray ionization-mass spectrometry (ESI-MS) methods. The pK(a)'s of N(2)(etLH)(2), N(2)(prLH)(2), and N(3)(etLH)(3), were determined spectrophotometrically and potentiometrically. The Fe(III) complex stability constants for the tetradentate N(2)(etLH)(2) and N(2)(prLH)(2), and hexadentate N(3)(etLH)(3), were measured by spectrophotometric and potentiometric titration, and by competition with ethylenediaminetetraacetic acid (EDTA). N(3)(etLH)(3) forms a 1:1 complex with Fe(III) with log β(110) = 27.34 ± 0.04. N(2)(prLH)(2) forms a 3:2 L:Fe complex with Fe(III) where log β(230) = 60.46 ± 0.04 and log β(110) = 20.39 ± 0.02. While N(2)(etLH)(2) also forms a 3:2 L:Fe complex with Fe(III), solubility problems precluded determining log β(230); log β(110) was found to be 20.45 ± 0.04. The pFe values of 26.5 for N(3)(etLH)(3) and 24.78 for N(2)(prLH)(2) are comparable to other siderophore molecules used in the treatment of iron overload, suggesting that these hydroxypyridinone ligands may be useful in the development of new chelation therapy agents.

  17. Elimination of polarity in the carotenoid terminus promotes the exposure of B850-binding sites (Tyr 44, 45) and ANS-mediated energy transfer in LH2 complexes of Rhodobacter sphaeroides.

    PubMed

    Liu, Yuan; Wu, Yongqiang; Xu, Chunhe

    2004-12-10

    Carotenoids in the peripheral light-harvesting complexes (LH2) of the green mutant (GM309) of Rhodobacter sphaeroides were identified as containing neurosporenes, which lack the polar CH(3)O group, compared to spheroidenes in native-LH2 of R. sphaeroides 601. After LH2 complexes were treated with 1-anilino-8-naphthalene sulfonate (ANS), new energy transfer pathways from ANS or tryptophan to carotenoids were discovered in both native- and GM309-LH2. The carotenoid fluorescence intensity of GM309-LH2 was greater than that of native-LH2 when bound with ANS, suggesting that the elimination of polarity in the neurosporene increases the energy transfer from ANS to carotenoid. The fact that two alpha-tyrosines (alpha-Tyr 44, 45, B850-binding sites) in each alpha-apoprotein of GM309-LH2 were more easily modified than those of native-LH2 by N-acetylimidazole (NAI) indicates that the elimination of polarity in the neurosporene terminus increases the exposure of these sites to solution.

  18. Time-dependent Occurrence Rate of Electromagnetic Cyclotron Waves in the Solar Wind: Evidence for the Effect of Alpha Particles?

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhao, G. Q.; Feng, H. Q.; Wu, D. J.

    Previous studies revealed that electromagnetic cyclotron waves (ECWs) near the proton cyclotron frequency exist widely in the solar wind, and the majority of ECWs are left-handed (LH) polarized waves. Using the magnetic field data from the STEREO mission, this Letter carries out a survey of ECWs over a long period of 7 years and calculates the occurrence rates of ECWs with different polarization senses. Results show that the occurrence rate is nearly a constant for the ECWs with right-handed polarization, but it varies significantly for the ECWs with LH polarization. Further investigation of plasma conditions reveals that the LH ECWsmore » take place preferentially in a plasma characterized by higher temperature, lower density, and larger velocity. Some considerable correlations between the occurrence rate of LH ECWs and the properties of ambient plasmas are discussed. The present research may provide evidence for the effect of alpha particles on the generation of ECWs.« less

  19. Exciton binding energy in a pyramidal quantum dot

    NASA Astrophysics Data System (ADS)

    Anitha, A.; Arulmozhi, M.

    2018-05-01

    The effects of spatially dependent effective mass, non-parabolicity of the conduction band and dielectric screening function on exciton binding energy in a pyramid-shaped quantum dot of GaAs have been investigated by variational method as a function of base width of the pyramid. We have assumed that the pyramid has a square base with area a× a and height of the pyramid H=a/2. The trial wave function of the exciton has been chosen according to the even mirror boundary condition, i.e. the wave function of the exciton at the boundary could be non-zero. The results show that (i) the non-parabolicity of the conduction band affects the light hole (lh) and heavy hole (hh) excitons to be more bound than that with parabolicity of the conduction band, (ii) the dielectric screening function (DSF) affects the lh and hh excitons to be more bound than that without the DSF and (iii) the spatially dependent effective mass (SDEM) affects the lh and hh excitons to be less bound than that without the SDEM. The combined effects of DSF and SDEM on exciton binding energy have also been calculated. The results are compared with those available in the literature.

  20. Femtosecond spectroscopy of native and carotenoidless purple-bacterial LH2 clarifies functions of carotenoids.

    PubMed

    Theiss, Christoph; Leupold, Dieter; Moskalenko, Andrei A; Razjivin, Andrei P; Eichler, Hans J; Lokstein, Heiko

    2008-06-01

    EET between the two circular bacteriochlorophyll compartments B800 and B850 in native (containing the carotenoid rhodopin) and carotenoidless LH2 isolated from the photosynthetic purple sulfur bacterium Allochromatium minutissimum was investigated by femtosecond time-resolved transient absorption spectroscopy. Both samples were excited with 120-fs laser pulses at 800 nm, and spectral evolution was followed in the 720-955 nm range at different delay times. No dependence of transient absorption in the B800 band on the presence of the carotenoid rhodopin was found. Together with the likewise virtually unchanged absorption spectra in the bacteriochlorophyll Q(y) region, these observations suggest that absence of rhodopin does not significantly alter the structure of the pigment-protein complex including interactions between bacteriochlorophylls. Apparently, rhodopin does also not accelerate B800 to B850 EET in LH2, contrary to what has been suggested previously. Moreover, "carotenoid-catalyzed internal conversion" can also be excluded for the bacteriochlorophylls in LH2 of A. minutissimum. Together with previous results obtained with two-photon fluorescence excitation spectroscopy, it can also be concluded that there is neither EET from rhodopin to B800 nor (back-)EET from B800 to rhodopin.

  1. Energy transfer in purple bacterial photosynthetic units from cells grown in various light intensities.

    PubMed

    Niedzwiedzki, Dariusz M; Gardiner, Alastair T; Blankenship, Robert E; Cogdell, Richard J

    2018-05-03

    Three photosynthetic membranes, called intra-cytoplasmic membranes (ICMs), from wild-type and the ∆pucBA abce mutant of the purple phototrophic bacterium Rps. palustris were investigated using optical spectroscopy. The ICMs contain identical light-harvesting complex 1-reaction centers (LH1-RC) but have various spectral forms of light-harvesting complex 2 (LH2). Spectroscopic studies involving steady-state absorption, fluorescence, and femtosecond time-resolved absorption at room temperature and at 77 K focused on inter-protein excitation energy transfer. The studies investigated how energy transfer is affected by altered spectral features of the LH2 complexes as those develop under growth at different light conditions. The study shows that LH1 → LH2 excitation energy transfer is strongly affected if the LH2 complex alters its spectroscopic signature. The LH1 → LH2 excitation energy transfer rate modeled with the Förster mechanism and kinetic simulations of transient absorption of the ICMs demonstrated that the transfer rate will be 2-3 times larger for ICMs accumulating LH2 complexes with the classical B800-850 spectral signature (grown in high light) compared to the ICMs from the same strain grown in low light. For the ICMs from the ∆pucBA abce mutant, in which the B850 band of the LH2 complex is blue-shifted and almost degenerate with the B800 band, the LH1 → LH2 excitation energy transfer was not observed nor predicted by calculations.

  2. Effects of luteinizing hormone and human chorionic gonadotropin on corpus luteum cells in a spheroid cell culture system.

    PubMed

    Walz, A; Keck, C; Weber, H; Kissel, C; Pietrowski, D

    2005-09-01

    The human corpus luteum (CL) is a highly vascularized, temporarily active endocrine gland and consists mainly of granulosa cells (GCs), theca cells (TCs), and endothelial cells (ECs). Its cyclic growth and development takes place under the influence of gonadotropic hormones. If pregnancy does occur, human chorionic gonadotropin (hCG) takes over the function of luteinizing hormone (LH) and, in contrast to LH, extends the functional life span of the CL. In this study, we investigated the effects of hCG and LH in a spheroidal cell culture model of CL development. Our data indicate that GCs secrete factors under the control of hCG that increase sprout formation of EC-spheroids. We demonstrate that the most prominent of these factors is VEGF-A. Furthermore, we found that both LH and hCG decrease sprout formation of GC-spheroids. After forming EC-GC coculture spheroids and consequently bringing GCs and ECs in close contact, sprouting increased under the influence of hCG, however not under LH. These experiments provide evidence for an hCG dependent functional switch in the GCs after coming in contact with ECs. Moreover, it demonstrates the considerably different effects of hCG and LH on GCs although their signaling is transmitted via the same receptor.

  3. Role of D1- and D2-like dopaminergic receptors in the nucleus accumbens in modulation of formalin-induced orofacial pain: Involvement of lateral hypothalamus.

    PubMed

    Shafiei, Iman; Vatankhah, Mahsaneh; Zarepour, Leila; Ezzatpanah, Somayeh; Haghparast, Abbas

    2018-05-01

    The role of dopaminergic system in modulation of formalin-induced orofacial nociception has been established. The present study aims to investigate the role of dopaminergic receptors in the nucleus accumbens (NAc) in modulation of nociceptive responses induced by formalin injection in the orofacial region. One hundred and six male Wistar rats were unilaterally implanted with two cannulae into the lateral hypothalamus (LH) and NAc. Intra-LH microinjection of carbachol, a cholinergic receptor agonist, was done 5min after intra-accumbal administration of different doses of SCH23390 (D1-like receptor antagonist) or sulpiride (D2-like receptor antagonist). After 5min, 50μl of 1% formalin was subcutaneously injected into the upper lip for inducing the orofacial pain. Carbachol alone dose-dependently reduced both phases of the formalin-induced orofacial pain. Intra-accumbal administration of SCH23390 (0.25, 1 and 4μg/0.5μl saline) or sulpiride (0.25, 1 and 4μg/0.5μl DMSO) before LH stimulation by carbachol (250nM/0.5μl saline) antagonized the antinociceptive responses during both phases of orofacial formalin test. The effects of D1- and D2-like receptor antagonism on the LH stimulation-induced antinociception were almost similar during the early phase. However, compared to D1-like receptor antagonism, D2-like receptor antagonism was a little more effective but not significant, at blocking the LH stimulation-induced antinociception during the late phase of formalin test. The findings revealed that there is a direct or indirect neural pathway from the LH to the NAc which is at least partially contributed to the modulation of formalin-induced orofacial nociception through recruitment of both dopaminergic receptors in this region. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Spectroscopic and biological studies of new mononuclear metal complexes of a bidentate NN and NO hydrazone-oxime ligand derived from egonol

    NASA Astrophysics Data System (ADS)

    Babahan, Ilknur; Emirdağ-Öztürk, Safiye; Poyrazoğlu-Çoban, Esin

    2015-04-01

    A novel ligand, vicinal dioxime ligand (egonol-hydrazone glyoxime) (LH2) was synthesized and characterized using 1H NMR, 13C NMR, MS, AAS, infrared spectroscopy, and magnetic susceptibility measurements. Mononuclear nickel (II), copper (II) and cobalt (II) complexes with a metal:ligand ratio of 1:2 for LH2 were also synthesized. Zn(II) forms complex [Zn(LH)Cl2] with a metal to ligand ratio of 1:1. IR spectrum shows that the ligand act in a bidentate manner and coordinates N4 donor groups of the ligands to NiII, CuII, CoII and ZnII ions. The detection of H-bonding (Osbnd H⋯O) in the [M(LH)2] metal complexes by IR spectra supported the square-planar MN4 coordination of Ni(II), Cu(II) and Co(II) complexes. The antimicrobial activities of compounds LH2 and their Ni(II), Cu(II), Co(II) and Zn(II) complexes were evaluated using the disc diffusion method against 16 bacteria and 5 yeasts. The minimal inhibitory concentrations (MICs) against all the bacteria and yeasts were also determined. Among the attempted test compounds, it is showed that all the compounds (L, LH2, [Ni(LH)2], [Cu(LH)2], [Co(LH)2(H2O)2], [Zn(LH)Cl2]) were effective against used test microorganisms.

  5. Dynamics of energy transfer from lycopene to bacteriochlorophyll in genetically-modified LH2 complexes of Rhodobacter sphaeroides.

    PubMed

    Hörvin Billsten, H; Herek, J L; Garcia-Asua, G; Hashøj, L; Polívka, T; Hunter, C N; Sundström, V

    2002-03-26

    LH2 complexes from Rb. sphaeroides were modified genetically so that lycopene, with 11 saturated double bonds, replaced the native carotenoids which contain 10 saturated double bonds. Tuning the S1 level of the carotenoid in LH2 in this way affected the dynamics of energy transfer within LH2, which were investigated using both steady-state and time-resolved techniques. The S1 energy of lycopene in n-hexane was determined to be approximately 12 500 +/- 150 cm(-1), by direct measurement of the S1-S2 transient absorption spectrum using a femtosecond IR-probing technique, thus placing an upper limit on the S1 energy of lycopene in the LH2 complex. Fluorescence emission and excitation spectra demonstrated that energy can be transferred from lycopene to the bacteriochlorophyll molecules within this LH2 complex. The energy-transfer dynamics within the mutant complex were compared to wild-type LH2 from Rb. sphaeroides containing the carotenoid spheroidene and from Rs. molischianum, in which lycopene is the native carotenoid. The results show that the overall efficiency for Crt --> B850 energy transfer is approximately 80% in lyco-LH2 and approximately 95% in WT-LH2 of Rb. sphaeroides. The difference in overall Crt --> BChl transfer efficiency of lyco-LH2 and WT-LH2 mainly relates to the low efficiency of the Crt S(1) --> BChl pathway for complexes containing lycopene, which was 20% in lyco-LH2. These results show that in an LH2 complex where the Crt S1 energy is sufficiently high to provide efficient spectral overlap with both B800 and B850 Q(y) states, energy transfer via the Crt S1 state occurs to both pigments. However, the introduction of lycopene into the Rb. sphaeroides LH2 complex lowers the S1 level of the carotenoid sufficiently to prevent efficient transfer of energy to the B800 Q(y) state, leaving only the Crt S1 --> B850 channel, strongly suggesting that Crt S1 --> BChl energy transfer is controlled by the relative Crt S1 and BChl Q(y) energies.

  6. Effect of 3,3',5-triiodothyronine and 3,5-diiodothyronine on progesterone production, cAMP synthesis, and mRNA expression of STAR, CYP11A1, and HSD3B genes in granulosa layer of chicken preovulatory follicles.

    PubMed

    Sechman, A; Pawlowska, K; Hrabia, A

    2011-10-01

    In vitro studies were performed to assess whether stimulatory effects of triiodothyronine (T3) on progesterone (P4) production in a granulosa layer (GL) of chicken preovulatory follicles are associated with 3',5'-cyclic adenosine monophosphate (cAMP) synthesis and mRNA expression of STAR protein, CYP11A1, and HSD3B. Effects of 3,5-diiodothyronine (3,5-T2) on steroidogenic function in these follicles were also investigated. The GL of F3 to F1 follicles was incubated in medium supplemented with T3 or 3,5-T2, LH, or forskolin (F), and a combination of each iodothyronine with LH or F. Levels of P4 and cAMP in culture media were determined by RIA. Expression of genes involved in P4 synthesis (ie, STAR protein, CYP11A1, and HSD3B) in the GL of F3 to F1 follicles incubated in medium with T3 or 3,5-T2 and their combination with LH was performed by real-time PCR. Triiodothyronine increased basal and LH- and F-stimulated P4 secretion by preovulatory follicles. The 3,5-T2 elevated P4 synthesis by F3, had no effect on F2 follicles, and diminished P4 production by the GL of F1 follicles. It had no effect on LH-stimulated P4 production; however, it augmented F-stimulated P4 production by F2 and F1 follicles. Although T3 did not affect basal and F-stimulated cAMP synthesis by the GL of preovulatory follicles, it increased LH-stimulated synthesis of this nucleotide. However, 3,5-T2 elevated F-stimulated cAMP synthesis in F3 and F2 follicles; it did not change basal and LH-stimulated cAMP production. Triiodothyronine decreased basal STAR and CYP11A1 mRNAs in F3 follicles, increased them in F1 follicles, and elevated HSD3B mRNA levels in F1 follicles. Triiodothyronine augmented LH-stimulated STAR, CYP11A1, and HSD3B mRNA levels in F2 and CYP11A1 in F1 follicles. However, T3 decreased LH-stimulated STAR and HSD3B mRNA levels in F1 follicles. The 3,5-T2 did not affect basal STAR and CYP11A1 mRNA expression in all investigated follicles; however, it decreased LH-stimulated STAR expression in F2 and F1 ones. The effects of 3,5-T2 caused elevated basal but diminished LH-stimulated HSD3B mRNA levels. In conclusion, data indicate that both iodothyronines are involved in P4 production in the GL of chicken preovulatory follicles acting alone and additively with LH. Effects of iodothyronines depend on follicle maturation and are associated with modulation of cAMP synthesis and STAR, CYP11A1, and HSD3B mRNA expression. We suggest that iodothyronines participate in maturation and ovulation of chicken follicles. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. The VLT-FLAMES survey of massive stars: wind properties and evolution of hot massive stars in the Large Magellanic Cloud

    NASA Astrophysics Data System (ADS)

    Mokiem, M. R.; de Koter, A.; Evans, C. J.; Puls, J.; Smartt, S. J.; Crowther, P. A.; Herrero, A.; Langer, N.; Lennon, D. J.; Najarro, F.; Villamariz, M. R.; Vink, J. S.

    2007-04-01

    We have studied the optical spectra of a sample of 28 O- and early B-type stars in the Large Magellanic Cloud, 22 of which are associated with the young star forming region N11. Our observations sample the central associations of LH9 and LH10, and the surrounding regions. Stellar parameters are determined using an automated fitting method (Mokiem et al. 2005), which combines the stellar atmosphere code fastwind (Puls et al. 2005) with the genetic algorithm based optimisation routine pikaia (Charbonneau 1995). We derive an age of 7.0 ± 1.0 and 3.0 ± 1.0 Myr for LH9 and LH10, respectively. The age difference and relative distance of the associations are consistent with a sequential star formation scenario in which stellar activity in LH9 triggered the formation of LH10. Our sample contains four stars of spectral type O2. From helium and hydrogen line fitting we find the hottest three of these stars to be 49{-}54 kK (compared to 45{-}46 kK for O3 stars). Detailed determination of the helium mass fraction reveals that the masses of helium enriched dwarfs and giants derived in our spectroscopic analysis are systematically lower than those implied by non-rotating evolutionary tracks. We interpret this as evidence for efficient rotationally enhanced mixing leading to the surfacing of primary helium and to an increase of the stellar luminosity. This result is consistent with findings for SMC stars by Mokiem et al. (2006). For bright giants and supergiants no such mass discrepancy is found; these stars therefore appear to follow tracks of modestly or non-rotating objects. The set of programme stars was sufficiently large to establish the mass loss rates of OB stars in this Z ˜ 1/2 Z⊙ environment sufficiently accurate to allow for a quantitative comparison with similar objects in the Galaxy and the SMC. The mass loss properties are found to be intermediate to massive stars in the Galaxy and SMC. Comparing the derived modified wind momenta D_mom as a function of luminosity with predictions for LMC metallicities by Vink et al. (2001) yields good agreement in the entire luminosity range that was investigated, i.e. 5.0 < log L/L⊙< 6.1. Appendix A is only available in electronic form at http://www.aanda.org

  8. Stark absorption spectroscopy on the carotenoids bound to B800-820 and B800-850 type LH2 complexes from a purple photosynthetic bacterium, Phaeospirillum molischianum strain DSM120.

    PubMed

    Horibe, Tomoko; Qian, Pu; Hunter, C Neil; Hashimoto, Hideki

    2015-04-15

    Stark absorption spectroscopy was applied to clarify the structural differences between carotenoids bound to the B800-820 and B800-850 LH2 complexes from a purple photosynthetic bacterium Phaeospirillum (Phs.) molischianum DSM120. The former complex is produced when the bacteria are grown under stressed conditions of low temperature and dim light. These two LH2 complexes bind carotenoids with similar composition, 10% lycopene and 80% rhodopin, each with the same number of conjugated CC double bonds (n=11). Quantitative classical and semi-quantum chemical analyses of Stark absorption spectra recorded in the carotenoid absorption region reveal that the absolute values of the difference dipole moments |Δμ| have substantial differences (2 [D/f]) for carotenoids bound to either B800-820 or B800-850 complexes. The origin of this striking difference in the |Δμ| values was analyzed using the X-ray crystal structure of the B800-850 LH2 complex from Phs. molischianum DSM119. Semi-empirical molecular orbital calculations predict structural deformations of the major carotenoid, rhodopin, bound within the B800-820 complex. We propose that simultaneous rotations around neighboring CC and CC bonds account for the differences in the 2 [D/f] of the |Δμ| value. The plausible position of the rotation is postulated to be located around C21-C24 bonds of rhodopin. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Regional and temporal differences in gene expression of LH(BETA)T(AG) retinoblastoma tumors.

    PubMed

    Houston, Samuel K; Pina, Yolanda; Clarke, Jennifer; Koru-Sengul, Tulay; Scott, William K; Nathanson, Lubov; Schefler, Amy C; Murray, Timothy G

    2011-07-23

    The purpose of this study was to evaluate by microarray the hypothesis that LH(BETA)T(AG) retinoblastoma tumors exhibit regional and temporal variations in gene expression. LH(BETA)T(AG) mice aged 12, 16, and 20 weeks were euthanatized (n = 9). Specimens were taken from five tumor areas (apex, anterior lateral, center, base, and posterior lateral). Samples were hybridized to gene microarrays. The data were preprocessed and analyzed, and genes with a P < 0.01, according to the ANOVA models, and a log(2)-fold change >2.5 were considered to be differentially expressed. Differentially expressed genes were analyzed for overlap with known networks by using pathway analysis tools. There were significant temporal (P < 10(-8)) and regional differences in gene expression for LH(BETA)T(AG) retinoblastoma tumors. At P < 0.01 and log(2)-fold change >2.5, there were significant changes in gene expression of 190 genes apically, 84 genes anterolaterally, 126 genes posteriorly, 56 genes centrally, and 134 genes at the base. Differentially expressed genes overlapped with known networks, with significant involvement in regulation of cellular proliferation and growth, response to oxygen levels and hypoxia, regulation of cellular processes, cellular signaling cascades, and angiogenesis. There are significant temporal and regional variations in the LH(BETA)T(AG) retinoblastoma model. Differentially expressed genes overlap with key pathways that may play pivotal roles in murine retinoblastoma development. These findings suggest the mechanisms involved in tumor growth and progression in murine retinoblastoma tumors and identify pathways for analysis at a functional level, to determine significance in human retinoblastoma. Microarray analysis of LH(BETA)T(AG) retinal tumors showed significant regional and temporal variations in gene expression, including dysregulation of genes involved in hypoxic responses and angiogenesis.

  10. Radioimmunoassay of LH (in Japanese)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Motohashi, T.; Yogo, I.

    The methods of isolation of binding free hormones (B/F), the double antibody method, adsorption method (dextran charcoal method), and precipitation method (dioxane method) were compared for the RIA of LH in the blood. Comparison of the standard curves revealed no difference among the three methods within measurable limits. The dextran charcoal method, a rapid quantitative determination, tended to be inferior in the variation and reproducibility of intraassay. The dioxane method was shown to be an excellent method in the convenience of procedures, precision, and reproducibility, except for the disadvantage of using an antigen-antibody system which is heterologous to LH. Whenmore » changes in the LH values during menstrual cycles in normal Mature women were examined, a large increase was observed in the phase of ovulation. In case of the administration of Enavid, an oral contraceptive, large fluctuations occurred in the LH value, indicating that ovulation was accompanied by an increase in LR. Changes in the blood LH before, during, and after the administration of Clomid, aimed at ovulation induction, were observed. (Japan)« less

  11. How nature designs light-harvesting antenna systems: design principles and functional realization in chlorophototrophic prokaryotes

    NASA Astrophysics Data System (ADS)

    Bryant, Donald A.; Canniffe, Daniel P.

    2018-02-01

    Chlorophyll-based phototrophs, or chlorophototrophs, convert light energy into stored chemical potential energy using two types of photochemical reaction center (RC), denoted type-1 and type-2. After excitation with light, a so-called special pair of chlorophylls in the RC is oxidized, and an acceptor is reduced. To ensure that RCs function at maximal rates in diffuse and variable light conditions, chlorophototrophs have independently evolved diverse light-harvesting antenna systems to rapidly and efficiently transfer that energy to the RCs. Energy transfer between weakly coupled chromophores is generally believed to proceed by resonance energy transfer, a dipole-induced-dipole process that was initially described theoretically by Förster. Nature principally optimizes three parameters in antenna systems: the distance separating the donor and acceptor chromophores, the relative orientations of those chromophores, and the spectral overlap between the donor and the acceptor chromophores. However, there are other important biological parameters that nature has optimized, and some common themes emerge from comparisons of different antenna systems. This tutorial considers structural and functional characteristics of three fundamentally different light-harvesting antenna systems of chlorophotrophic bacteria: phycobilisomes of cyanobacteria, the light-harvesting complexes (LH1 and LH2) of purple bacteria, and chlorosomes of green bacteria. Phycobilisomes are generally considered to represent an antenna system in which the chromophores are weakly coupled, while the strongly coupled bacteriochlorophyll molecules in LH1 and LH2 are strongly coupled and are better described by exciton theory. Chlorosomes can contain up to 250 000 bacteriochlorophyll molecules, which are very strongly coupled and form supramolecular, nanotubular arrays. The general and specific principles that have been optimized by natural selection during the evolution of these diverse light-harvesting antenna systems are discussed.

  12. Distribution of rhodopin and spirilloxanthin between LH1 and LH2 complexes when incorporating carotenoid mixture into the membrane of purple sulfur bacterium Allochromatium minutissimum in vitro.

    PubMed

    Bolshakov, M A; Ashikhmin, A A; Makhneva, Z K; Moskalenko, A A

    2016-11-01

    Carotenoid mixture enriched by rhodopin and spirilloxanthin was incorporated in LH2 and LH1 complexes from Allochromatium (Alc.) minutissimum in vitro. The maximum incorporating level was ~95%. Rhodopin (56.4%) and spirilloxanthin (13.8%) were incorporated into the LH1 complex, in contrast to the control complex, which contained primarily spirilloxanthin (66.8%). After incorporating, the LH2 complex contained rhodopin (66.7%) and didehydrorhodopin (14.6%), which was close to their content in the control (67.4 and 20.5%, respectively). Thus, it was shown that carotenoids from the total pool are not selectively incorporated into LH2 and LH1 complexes in vitro in the proportion corresponding to the carotenoid content in the complexes in vivo.

  13. Population pharmacokinetics of perphenazine in schizophrenia patients from CATIE: impact of race and smoking.

    PubMed

    Jin, Yuyan; Pollock, Bruce G; Coley, Kim; Miller, Del; Marder, Stephen R; Florian, Jeff; Schneider, Lon; Lieberman, Jeffrey; Kirshner, Margaret; Bies, Robert R

    2010-01-01

    The goal of the study was to characterize population pharmacokinetics (PPK) for perphenazine in patients with schizophrenia from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). Patients (n = 156) received 8 to 32 mg of perphenazine daily for 14 to 600 days for a total of 421 plasma concentrations measurements. Nonlinear mixed-effects modeling was used to determine PPK characteristics of perphenazine. One- and 2-compartment models with various random effect implementations and mixture distributions were evaluated. Objective function values and goodness-of-fit plots were used as model selection criteria. Age, weight, sex, race, smoking, and concomitant medications were evaluated as covariates. A 1-compartment linear model with proportional error best described the data. The population mean clearance and volume of distribution for perphenazine were 483 L/h and 18 200 L, respectively. Race and smoking status had significant impacts on perphenazine clearance estimates. In addition, the estimated population mean clearance was 48% higher in nonsmoking African Americans than in nonsmoking other races (512 L/h vs 346 L/h). Active smokers eliminated perphenazine 159 L/h faster than nonsmokers in each race. Clearances for smoking African Americans versus smokers in other races were 671 L/h versus 505 L/h, respectively.

  14. Comparison of the fluorescence kinetics of detergent-solubilized and membrane-reconstituted LH2 complexes from Rps. acidophila and Rb. sphaeroides.

    PubMed

    Pflock, Tobias; Dezi, Manuela; Venturoli, Giovanni; Cogdell, Richard J; Köhler, Jürgen; Oellerich, Silke

    2008-01-01

    Picosecond time-resolved fluorescence spectroscopy has been used in order to compare the fluorescence kinetics of detergent-solubilized and membrane-reconstituted light-harvesting 2 (LH2) complexes from the purple bacteria Rhodopseudomonas (Rps.) acidophila and Rhodobacter (Rb.) sphaeroides. LH2 complexes were reconstituted in phospholipid model membranes at different lipid:protein-ratios and all samples were studied exciting with a wide range of excitation densities. While the detergent-solubilized LH2 complexes from Rps. acidophila showed monoexponential decay kinetics (tau(f )= 980 ps) for excitation densities of up to 3.10(13) photons/(pulse.cm(2)), the membrane-reconstituted LH2 complexes showed multiexponential kinetics even at low excitation densities and high lipid:protein-ratios. The latter finding indicates an efficient clustering of LH2 complexes in the phospholipid membranes. Similar results were obtained for the LH2 complexes from Rb. sphaeroides.

  15. Molecular assessment of microbiota structure and dynamics along mixed olive oil and winery wastewaters biotreatment.

    PubMed

    Eusébio, Ana; Tacão, Marta; Chaves, Sandra; Tenreiro, Rogério; Almeida-Vara, Elsa

    2011-07-01

    The major parcel of the degradation occurring along wastewater biotreatments is performed either by the native microbiota or by added microbial inocula. The main aim of this study was to apply two fingerprinting methods, temperature gradient gel electrophoresis (TGGE) and length heterogeneity-PCR (LH-PCR) analysis of 16S rRNA gene fragments, in order to assess the microbiota structure and dynamics during mixed olive oil and winery wastewaters aerobic biotreatment performed in a jet-loop reactor (JLR). Sequence homology analysis showed the presence of bacterial genera Gluconacetobacter, Klebsiella, Lactobacillus, Novosphingobium, Pseudomonas, Prevotella, Ralstonia, Sphingobium and Sphingomonas affiliated with five main phylogenetic groups: alpha-, beta- and gamma-Proteobacteria, Firmicutes and Bacteroidetes. LH-PCR analysis distinguished eight predominant DNA fragments correlated with the samples showing highest performance (COD removal rates of 67 up to 75%). Cluster analysis of both TGGE and LH-PCR fingerprinting profiles established five main clusters, with similarity coefficients higher than 79% (TGGE) and 62% (LH-PCR), and related with hydraulic retention time, indicating that this was the main factor responsible for the shifts in the microbiota structure. Canonical correspondence analysis revealed that changes observed on temperature and O(2) level were also responsible for shifts in microbiota composition. Community level metabolic profile analysis was used to test metabolic activities in samples. Integrated data revealed that the microbiota structure corresponds to bacterial groups with high degradative potential and good suitability for this type of effluents biotreatments.

  16. Functional Fault Modeling of a Cryogenic System for Real-Time Fault Detection and Isolation

    NASA Technical Reports Server (NTRS)

    Ferrell, Bob; Lewis, Mark; Perotti, Jose; Oostdyk, Rebecca; Brown, Barbara

    2010-01-01

    The purpose of this paper is to present the model development process used to create a Functional Fault Model (FFM) of a liquid hydrogen (L H2) system that will be used for realtime fault isolation in a Fault Detection, Isolation and Recover (FDIR) system. The paper explains th e steps in the model development process and the data products required at each step, including examples of how the steps were performed fo r the LH2 system. It also shows the relationship between the FDIR req uirements and steps in the model development process. The paper concl udes with a description of a demonstration of the LH2 model developed using the process and future steps for integrating the model in a live operational environment.

  17. Recognition memory reveals just how CONTRASTIVE contrastive accenting really is

    PubMed Central

    Fraundorf, Scott H.; Watson, Duane G.; Benjamin, Aaron S.

    2010-01-01

    The effects of pitch accenting on memory were investigated in three experiments. Participants listened to short recorded discourses that contained contrast sets with two items (e.g. British scientists and French scientists); a continuation specified one item from the set. Pitch accenting on the critical word in the continuation was manipulated between non-contrastive (H* in the ToBI system) and contrastive (L+H*). On subsequent recognition memory tests, the L+H* accent increased hits to correct statements and correct rejections of the contrast item (Experiments 1–3), but did not impair memory for other parts of the discourse (Experiment 2). L+H* also did not facilitate correct rejections of lures not in the contrast set (Experiment 3), indicating that contrastive accents do not simply strengthen the representation of the target item. These results suggest comprehenders use pitch accenting to encode and update information about multiple elements in a contrast set. PMID:20835405

  18. Critical Current Test of Liquid Hydrogen Cooled HTC Superconductors under External Magnetic Field

    NASA Astrophysics Data System (ADS)

    Shirai, Yasuyuki; Shiotsu, Masahiro; Tatsumoto, Hideki; Kobayashi, Hiroaki; Naruo, Yoshihiro; Nonaka, Satoshi; Inatani, Yoshifumi

    High-Tc (HTC) superconductors including MgB2 will show excellent properties under temperature of Liquid Hydrogen (LH2:20K), which has large latent heat and low viscosity coefficient. In order to design and fabricate the LH2 cooled superconducting energy devices, we must clear the cooling property of LH2 for superconductors, the cooling system and safety design of LH2 cooled superconducting devices and electro-magnetic property evaluation of superconductors (BSCCO, REBCO and MgB2) and their magnets cooled by LH2. As the first step of the study, an experimental setup which can be used for investigating heat transfer characteristics of LH2 in a pool and also in forced flow (circulation loop with a pump), and also for evaluation of electro-magnetic properties of LH2 cooled superconductors under external magnetic field (up to 7 T). In this paper, we will show a short sketch of the experimental set-up, practical experiences in safety operation of liquid hydrogen cooling system and example test results of critical current evaluation of HTC superconductors cooled by LH2.

  19. Fracture Mechanics Analysis of LH2 Feed Line Flow Liners

    NASA Technical Reports Server (NTRS)

    James, Mark A.; Dawicke, David S.; Brzowski, Matthew B.; Raju, Ivatury S.; Elliott, Kenny B.; Harris, Charles E.

    2006-01-01

    Inspections of the Space Shuttle Main Engine revealed fatigue cracks growing from slots in the flow liner of the liquid hydrogen (LH2) feed lines. During flight, the flow liners experience complex loading induced by flow of LH2 and the resonance characteristics of the structure. The flow liners are made of Inconel 718 and had previously not been considered a fracture critical component. However, fatigue failure of a flow liner could have catastrophic effect on the Shuttle engines. A fracture mechanics study was performed to determine if a damage tolerance approach to life management was possible and to determine the sensitivity to the load spectra, material properties, and crack size. The load spectra were derived separately from ground tests and material properties were obtained from coupon tests. The stress-intensity factors for the fatigue cracks were determined from a shell-dynamics approach that simulated the dominant resonant frequencies. Life predictions were obtained using the NASGRO life prediction code. The results indicated that adequate life could not be demonstrated for initial crack lengths of the size that could be detected by traditional NDE techniques.

  20. Single-molecule spectroscopy unmasks the lowest exciton state of the B850 assembly in LH2 from Rps. acidophila.

    PubMed

    Kunz, Ralf; Timpmann, Kõu; Southall, June; Cogdell, Richard J; Freiberg, Arvi; Köhler, Jürgen

    2014-05-06

    We have recorded fluorescence-excitation and emission spectra from single LH2 complexes from Rhodopseudomonas (Rps.) acidophila. Both types of spectra show strong temporal spectral fluctuations that can be visualized as spectral diffusion plots. Comparison of the excitation and emission spectra reveals that for most of the complexes the lowest exciton transition is not observable in the excitation spectra due to the cutoff of the detection filter characteristics. However, from the spectral diffusion plots we have the full spectral and temporal information at hand and can select those complexes for which the excitation spectra are complete. Correlating the red most spectral feature of the excitation spectrum with the blue most spectral feature of the emission spectrum allows an unambiguous assignment of the lowest exciton state. Hence, application of fluorescence-excitation and emission spectroscopy on the same individual LH2 complex allows us to decipher spectral subtleties that are usually hidden in traditional ensemble spectroscopy. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  1. Tissue-specific expression and regulation of the alternatively-spliced forms of lysyl hydroxylase 2 (LH2) in human kidney cells and skin fibroblasts.

    PubMed

    Walker, Linda C; Overstreet, Mayra A; Yeowell, Heather N

    2005-01-01

    Lysyl hydroxylases 1, 2, and 3 catalyse the hydroxylation of specific lysines in collagen. A small percentage of these hydroxylysine residues are precursors for the cross-link formation essential for the tensile strength of collagen. Lysyl hydroxylase 2 (LH2) exists as two alternatively-spliced forms; the long transcript (the major ubiquitously-expressed form) includes a 63 bp exon (13A) that is spliced out in the short form (expressed, together with the long form, in human kidney, spleen, liver, and placenta). This study shows that this alternative splicing event can be regulated by both cell density and cycloheximide (CHX). Although only the long form of LH2 is detected in untreated confluent human skin fibroblasts, after 24 h treatment with CHX the short LH2 transcript is also expressed. In kidney cells, in which both LH2 transcripts are equally expressed, the long LH2 transcript is significantly decreased after 24 h CHX treatment, whereas expression of the short transcript is slightly increased. This suggests that, in kidney cells, the splicing mechanism for the inclusion of exon 13A in LH2 requires a newly-synthesized protein factor that is suppressed by CHX, whereas, in skin fibroblasts in which levels of LH2 (long) are unaffected, CHX appears to suppress a factor that inhibits exclusion of exon 13A, thereby promoting expression of LH2 (short). As these alternate transcripts of LH2 may have specificity for hydroxylation of lysines in either telopeptide or helical collagen domains, their relative expression determines the type of cross-links formed, thereby affecting collagen strength. Therefore, any perturbation of the regulation of LH2 splicing could influence the stability of the extracellular matrix and contribute to specific connective tissue disorders.

  2. TAC1 Gene Products Regulate Pituitary Hormone Secretion and Gene Expression in Prepubertal Grass Carp Pituitary Cells.

    PubMed

    Hu, Guangfu; He, Mulan; Ko, Wendy K W; Wong, Anderson O L

    2017-06-01

    Tachykinin-1 (TAC1) is known to have diverse functions in mammals, but similar information is scarce in fish species. Using grass carp as a model, the pituitary actions, receptor specificity and postreceptor signaling of TAC1 gene products, namely substance P (SP) and neurokinin A (NKA), were examined. TAC1 encoding SP and NKA as well as tachykinin receptors NK1R and NK2R were cloned in the carp pituitary. The newly cloned receptors were shown to be functional with properties similar to mammalian counterparts. In carp pituitary cells, SP and NKA could trigger luteinizing hormone (LH), prolactin (PRL), and somatolactin α (SLα) secretion, with parallel rises in PRL and SLα transcripts. Short-term SP treatment (3 hours) induced LH release, whereas prolonged induction (24 hours) could attenuate LHβ messenger RNA (mRNA) expression. At pituitary cell level, LH, PRL, and SLα regulation by TAC1 gene products were mediated by NK1R, NK2R, and NK3R, respectively. Apparently, SP- and NKA-induced LH and SLα secretion and transcript expression were mediated by adenylyl cyclase/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA), phospholiphase C (PLC)/inositol 1,4,5-triphosphate/protein kinase C (PKC), and Ca2+/calmodulin (CaM)/CaM-dependent protein kinase-II pathways. The signal transduction for PRL responses was similar, except for the absence of a PKC component. Regarding SP inhibition of LHβ mRNA expression, the cAMP/PKA- and PLC/PKC-dependent (but not Ca2+/CaM-dependent) cascades were involved. These results, as a whole, suggest that TAC1 gene products play a role in LH, PRL, and SLα regulation via overlapping postreceptor signaling coupled to different subtypes of tachykinin receptor expressed in the carp pituitary. Copyright © 2017 Endocrine Society.

  3. Hg(ii) and Pd(ii) complexes with a new selenoether bridged biscarbene ligand: efficient mono- and bis-arylation of methyl acrylate with a pincer biscarbene Pd(ii) precatalyst.

    PubMed

    Rishu; Prashanth, Billa; Bawari, Deependra; Mandal, Ushnish; Verma, Aditya; Choudhury, Angshuman Roy; Singh, Sanjay

    2017-05-16

    Two equivalents of 1-benzyl-3-bromoethylbenzimidazolium bromide couple with Na 2 Se to produce the first selenoether bridged bis-benzimidazolium salt (LH 2 )Br 2 . The nitrate (LH 2 )(NO 3 ) 2 and tetrafluoroborate (LH 2 )(BF 4 ) 2 salts were also synthesized from (LH 2 )Br 2 . The reaction of Hg(OAc) 2 with (LH 2 )Br 2 gave the first pseudo pincer carbene mercury complex, [Hg(L-κ 2 C)][HgBr 4 ] (C1). Different complexes of Pd(ii) with selenoether bridged carbene were obtained using (LH 2 )Br 2 and (LH 2 )(NO 3 ) 2 . Syntheses of these complexes were dependent on the counter anion and the temperature. Thus, the pincer type ionic complex [PdBr(L-κ 3 CSeC)]Br (C2) was isolated at 80 °C and the pseudo pincer type neutral complex cis-[PdBr 2 (L-κ 2 C)] (C3) was isolated at room temperature from (LH 2 )Br 2 and Pd(OAc) 2 in DMSO. The nitrate precursor (LH 2 )(NO 3 ) 2 on palladation with Pd(OAc) 2 afforded [Pd(L-κ 4 C Bz CSeC)]NO 3 (C4) showing an unprecedented intramolecular metallation at the ortho position of the benzyl wingtip of the benzimidazole moiety. The ligand salts and metal complexes have been characterized using HRMS, heteronuclear NMR and IR spectroscopy. Single crystal X-ray structures of the ligand salts (LH 2 )Br 2 and (LH 2 )(BF 4 ) 2 and complexes C1-C4 have also been elucidated. Complex C2 showed good activity for C-C coupling in the mono-Heck reaction of methyl acrylate and arylbromides. Interestingly, the less common bis-arylation was also observed with deactivated arylbromides as the result of double-Heck coupling.

  4. Maternal postpartum learned helplessness (LH) affects maternal care by dams and responses to the LH test in adolescent offspring.

    PubMed

    Kurata, Akiko; Morinobu, Shigeru; Fuchikami, Manabu; Yamamoto, Shigeto; Yamawaki, Shigeto

    2009-06-01

    It is known that the early environment affects the mental development of rodent and human offspring. However, it is not known specifically whether a postpartum depressive state influences the depressive state in offspring. Using learned helplessness (LH) in rats as an animal model of depression, we examined the influence of maternal postpartum LH on responses to the LH test of offspring. Dam rats were judged as LH or non-helpless (nLH) on postnatal days (PN) 2-3, and maternal behavior was recorded during PN2-14. On PN 45-46, offspring were subjected to the LH test. Plasma corticosterone (CORT) levels, hippocampal levels of glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF) mRNA were measured before and after the LH test in offspring. Active nursing in LH dams was significantly lower than that in nLH dams. Susceptibility to LH in the offspring of LH dams was significantly higher than in those of nLH dams, and was negatively correlated with active nursing by LH dams. The GR mRNA levels before and after the LH test were lower in the offspring of LH dams than in those of nLH dams, and the reduced basal GR mRNA and protein might have resulted in the higher CORT response after the LH test. There was no significant difference in BDNF mRNA in the offspring of LH and nLH dams. These findings suggest that early postpartum LH decreased active nursing and increased depression-like behavior in the adolescent offspring via dysfunction of the hypothalamic-pituitary-adrenal axis.

  5. Regulation of LH/FSH expression by secretoglobin 3A2 in the mouse pituitary gland.

    PubMed

    Miyano, Yuki; Tahara, Shigeyuki; Sakata, Ichiro; Sakai, Takafumi; Abe, Hiroyuki; Kimura, Shioko; Kurotani, Reiko

    2014-04-01

    Secretoglobin (SCGB) 3A2 was originally identified as a downstream target for the homeodomain transcription factor NKX2-1 in the lung. NKX2-1 plays a role in the genesis and expression of genes in the thyroid, lung and ventral forebrain; Nkx2-1-null mice have no thyroid and pituitary and severely hypoplastic lungs and hypothalamus. To demonstrate whether SCGB3A2 plays any role in pituitary hormone production, NKX2-1 and SCGB3A2 expression in the mouse pituitary gland was examined by immunohistochemical analysis and RT-PCR. NKX2-1 was localized in the posterior pituitary lobe, whereas SCGB3A2 was observed in both anterior and posterior lobes as shown by immunohistochemistry and RT-PCR. Expression of CCAAT-enhancer binding proteins (C/EBPs), which regulate mouse Scgb3a2 transcription, was also examined by RT-PCR. C/EBPβ, γ, δ and ζ were expressed in the adult mouse pituitary gland. SCGB3A2 was expressed in the anterior and posterior lobes from postnatal days 1 and 5, respectively and the areas where SCGB3A2 expression was found coincided with the area where FSH-secreting cells were found. Double-staining for SCGB3A2 and pituitary hormones revealed that SCGB3A2 was mainly localized in gonadotrophs in 49 % of FSH-secreting cells and 47 % of LH-secreting cells. In addition, SCGB3A2 dramatically inhibited LH and FSH mRNA expression in rat pituitary primary cell cultures. These results suggest that SCGB3A2 regulates FSH/LH production in the anterior pituitary lobe and that transcription factors other than NKX2-1 may regulate SCGB3A2 expression.

  6. Transient dwarfism and hypogonadism in mice lacking Otx1 reveal prepubescent stage-specific control of pituitary levels of GH, FSH and LH.

    PubMed

    Acampora, D; Mazan, S; Tuorto, F; Avantaggiato, V; Tremblay, J J; Lazzaro, D; di Carlo, A; Mariano, A; Macchia, P E; Corte, G; Macchia, V; Drouin, J; Brûlet, P; Simeone, A

    1998-04-01

    Genetic and molecular approaches have enabled the identification of regulatory genes critically involved in determining cell types in the pituitary gland and/or in the hypothalamus. Here we report that Otx1, a homeobox-containing gene of the Otx gene family, is postnatally transcribed and translated in the pituitary gland. Cell culture experiments indicate that Otx1 may activate transcription of the growth hormone (GH), follicle-stimulating hormone (betaFSH), luteinizing hormone (betaLH) and alpha-glycoprotein subunit (alphaGSU) genes. Analysis of Otx1 null mice indicates that, at the prepubescent stage, they exhibit transient dwarfism and hypogonadism due to low levels of pituitary GH, FSH and LH hormones which, in turn, dramatically affect downstream molecular and organ targets. Nevertheless, Otx1-/- mice gradually recover from most of these abnormalities, showing normal levels of pituitary hormones with restored growth and gonadal function at 4 months of age. Expression patterns of related hypothalamic and pituitary cell type restricted genes, growth hormone releasing hormone (GRH), gonadotropin releasing hormone (GnRH) and their pituitary receptors (GRHR and GnRHR) suggest that, in Otx1-/- mice, hypothalamic and pituitary cells of the somatotropic and gonadotropic lineages appear unaltered and that the ability to synthesize GH, FSH and LH, rather than the number of cells producing these hormones, is affected. Our data indicate that Otx1 is a new pituitary transcription factor involved at the prepubescent stage in the control of GH, FSH and LH hormone levels and suggest that a complex regulatory mechanism might exist to control the physiological need for pituitary hormones at specific postnatal stages.

  7. Betacarotene supplementation increases ovulation rate without an increment in LH secretion in cyclic goats.

    PubMed

    Meza-Herrera, Cesar A; Vargas-Beltran, Fermin; Vergara-Hernandez, Hector P; Macias-Cruz, Ulises; Avendaño-Reyes, Leonel; Rodriguez-Martinez, Rafael; Arellano-Rodriguez, Gerardo; Veliz-Deras, Francisco G

    2013-03-01

    This study aimed to evaluate the effects of betacarotene (BC) supplementation on ovulation rate (OR) and luteinizing hormone (LH) secretion in adult goats during the breeding season. Additionally, total ovarian activity (TOA) comprising the total number of ultrasonographically detectable antral follicles (AF) and corpora lutea (OR) was also assessed. In early October, adult goats [n=22, 3.5 years of age, 7/8 Sannen-Alpine; 26°N, 103°W at 1117m.a.s.l.] were randomly assigned to: (i) BC group (BCG), orally supplemented with 50mg of BC/goat/day [n=10; live weight (LW)=45.9±2.0kg, body condition score (BCS; range: 0-emaciated to 5-obese)=3.0±0.1], and (ii) control group (CONT) [n=12; LW=46.2±2.0kg, BCS=3.0±0.1]. All animals received a basal diet of alfalfa hay, corn silage and corn grain, with free access to water and mineral salts. The whole experimental period spanned 34 days before and 17 days after ovulation. On day 23 of the experiment, estrus was synchronized with progestin-releasing intravaginal sponges; 36h prior to estrus, an intensive blood sampling (every 15min for 6h) was performed to determine mean LH concentrations, pulsatility (LH-PULSE) and area under the curve (LH-AUC) for serial LH concentrations. Afterwards, by the end of the luteal phase (i.e., 17 days after the onset of estrus), an ultrasonographic scanning was performed to evaluate OR and TOA [AF+OR]. The average LW and BCS did not differ (p>0.05) during the experimental period. BC-supplemented goats showed an increase in OR (3.4±0.2 versus 2.8±0.2; p<0.05) and exhibited lower (p<0.05) serum LH concentrations, LH-AUC and LH-PULSE compared to CONT. A positive correlation was recorded between OR and LW (r(2)=0.42, p<0.05) and BCS (r(2)=0.47, p<0.05). In addition, AF (5.0±0.6 versus 3.4±0.6) and TOA (8.4±0.6 versus 6.2±0.6) were greater (p<0.05) in the BC-supplemented group than CONT. Supplementation with BC enhanced ovarian follicular development and ovulation rate in adult female goats under decreased photoperiods through LHRH-independant pathways or direct effects of BC on ovarian function. Copyright © 2013 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  8. Proinflammatory Cytokine Infusion Attenuates LH's Feedforward on Testosterone Secretion: Modulation by Age

    PubMed Central

    Yang, Rebecca; Roelfsema, Ferdinand; Takahashi, Paul

    2016-01-01

    Context: In the experimental animal, inflammatory signals quench LH's feedforward drive of testosterone (T) secretion and appear to impair GnRH-LH output. The degree to which such suppressive effects operate in the human is not known. Objective: To test the hypothesis that IL-2 impairs LH's feedforward drive on T and T's feedback inhibition of LH secretion in healthy men. Setting: Mayo Center for Translational Science Activities. Patients or Other Participants: A total of 35 healthy men, 17 young and 18 older. Interventions: Randomized prospective double-blind saline-controlled study of IL-2 infusion in 2 doses with concurrent 10-minute blood sampling for 24 hours. Main Outcome Measures: Deconvolution analysis of LH and T secretion. Results: After saline injection, older compared with young men exhibited reduced LH feedforward drive on T secretion (P < .001), and decreased T feedback inhibition of LH secretion (P < .01). After IL-2 injection, LH's feedforward onto T secretion declined markedly especially in young subjects (P < .001). Concomitantly, IL-2 potentiated T's proportional feedback on LH secretion especially in older volunteers. Conclusion: This investigation confirms combined feedforward and feedback deficits in older relative to young men given saline and demonstrates 1) joint mechanisms by which IL-2 enforces biochemical hypogonadism, viz, combined feedforward block and feedback amplification; and 2) unequal absolute inhibition of T and LH secretion by IL-2 in young and older men. These outcomes establish that the male gonadal axis is susceptible to dual-site suppression by a prototypic inflammatory mediator. Thus, we postulate that selected ILs might also enforce male hypogonadism in chronic systemic inflammation. PMID:26600270

  9. Proinflammatory Cytokine Infusion Attenuates LH's Feedforward on Testosterone Secretion: Modulation by Age.

    PubMed

    Veldhuis, Johannes; Yang, Rebecca; Roelfsema, Ferdinand; Takahashi, Paul

    2016-02-01

    In the experimental animal, inflammatory signals quench LH's feedforward drive of testosterone (T) secretion and appear to impair GnRH-LH output. The degree to which such suppressive effects operate in the human is not known. To test the hypothesis that IL-2 impairs LH's feedforward drive on T and T's feedback inhibition of LH secretion in healthy men. Mayo Center for Translational Science Activities. A total of 35 healthy men, 17 young and 18 older. Randomized prospective double-blind saline-controlled study of IL-2 infusion in 2 doses with concurrent 10-minute blood sampling for 24 hours. Deconvolution analysis of LH and T secretion. After saline injection, older compared with young men exhibited reduced LH feedforward drive on T secretion (P < .001), and decreased T feedback inhibition of LH secretion (P < .01). After IL-2 injection, LH's feedforward onto T secretion declined markedly especially in young subjects (P < .001). Concomitantly, IL-2 potentiated T's proportional feedback on LH secretion especially in older volunteers. This investigation confirms combined feedforward and feedback deficits in older relative to young men given saline and demonstrates 1) joint mechanisms by which IL-2 enforces biochemical hypogonadism, viz, combined feedforward block and feedback amplification; and 2) unequal absolute inhibition of T and LH secretion by IL-2 in young and older men. These outcomes establish that the male gonadal axis is susceptible to dual-site suppression by a prototypic inflammatory mediator. Thus, we postulate that selected ILs might also enforce male hypogonadism in chronic systemic inflammation.

  10. Adult neurogenesis is reduced in the dorsal hippocampus of rats displaying learned helplessness behavior.

    PubMed

    Ho, Y C; Wang, S

    2010-11-24

    Clinical and preclinical studies suggest that the hippocampus has a role in the pathophysiology of major depression. In the learned helplessness (LH) animal model of depression after inescapable shocks (ISs) animals that display LH behavior have reduced cell proliferation in the hippocampus; this effect can be reversed by antidepressant treatment. Using this model, we compared rats that displayed LH behavior and rats that did not show LH behavior (NoLH) after ISs to determine whether reduced hippocampal cell proliferation is associated with the manifestation of LH behavior or is a general response to stress. Specifically, we examined cell proliferation, neurogenesis, and synaptic function in dorsal and ventral hippocampus of LH and NoLH animals and control rats that were not shocked. The LH rats had showed reduced cell proliferation, neurogenesis, and synaptic transmission in the dorsal hippocampus, whereas no changes were seen in the ventral hippocampus. These changes were not observed in the NoLH animals. In a group of NoLH rats that received the same amount of electrical shock as the LH rats to control for the unequal shocks received in these two groups, we observed changes in Ki-67(+) cells associated with acute stress. We conclude that reduced hippocampal cell proliferation and neurogenesis are associated with the manifestation of LH behavior and that the dorsal hippocampus is the most affected area. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. A scalable lysyl hydroxylase 2 expression system and luciferase-based enzymatic activity assay

    PubMed Central

    Guo, Hou-Fu; Cho, Eun Jeong; Devkota, Ashwini K.; Chen, Yulong; Russell, William; Phillips, George N.; Yamauchi, Mitsuo; Dalby, Kevin; Kurie, Jonathan M.

    2017-01-01

    Hydroxylysine aldehyde-derived collagen cross-links (HLCCs) accumulate in fibrotic tissues and certain types of cancer and are thought to drive the progression of these diseases. HLCC formation is initiated by lysyl hydroxylase 2 (LH2), an Fe(II) and α-ketoglutarate (αKG)-dependent oxygenase that hydroxylates telopeptidyl lysine residues on collagen. Development of LH2 antagonists for the treatment of these diseases will require a reliable source of recombinant LH2 protein and a non-radioactive LH2 enzymatic activity assay that is amenable to high throughput screens of small molecule libraries. However, LH2 protein generated previously using E coli– or insect-based expression systems was either insoluble or enzymatically unstable, and LH2 enzymatic activity assays have measured radioactive CO2 released from 14C-labeled αKG during its conversion to succinate. To address these deficiencies, we have developed a scalable process to purify human LH2 protein from Chinese hamster ovary cell-derived conditioned media samples and a luciferase-based assay that quantifies LH2-dependent conversion of αKG to succinate. These methodologies may be applicable to other Fe(II) and αKG-dependent oxygenase systems. PMID:28216326

  12. [Effects of ginger-separated moxibustion at Baliao points combined with Bushen Huoxue formula on patients with decreased ovarian reserve function].

    PubMed

    Jiang, Duosheng; Zhang, Yingchun; Wu, Xiaolan; Wang, Yanming; Fan, Qiangfang; Wu, Song

    2017-10-12

    To compare the efficacy differences between ginger-separated moxibustion at Baliao points combined with Bushen Huoxue formula and Bushen Huoxue formula alone on patients with decreased ovarian reserve function. Fifty patients of decreased ovarian reserve function were randomly divided into an observation group and a control group, 25 cases in each one. The patients in the observation group were treated with ginger-separated moxibustion at Baliao points combined with Bushen Huoxue formula; the moxibustion was given for 1.5 h, once every seven days, and no treatment was given during menstrual period. The patients in the control group were treated with Bushen Huoxue formula. One-month treatment was taken as one treatment course, and totally three courses were given. The change of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E 2 ), anti-mullerian hormone (AMH), antral follicle count (AFC), peak systolic velocity (PSV), resistance index (RI) were observed before and after treatment in the two groups. After treatment, the FSH, FSH/LH and RI were significantly lowered, but the E 2 , AFC, PSV were significantly increased in the two groups (all P <0.05); the FSH, FSH/LH and E 2 in the observation group were lower and AFC was higher than those in the control group (all P <0.05). The ginger-separated moxibustion at Baliao points combined with Bushen Huoxue formula are superior to Bushen Huoxue formula alone in improving ovarian reserve function.

  13. Kisspeptin Antagonists Reveal Kisspeptin 1 and Kisspeptin 2 Differential Regulation of Reproduction in the Teleost, Morone saxatilis.

    PubMed

    Zmora, Nilli; Stubblefield, John David; Wong, Ten-Tsao; Levavi-Sivan, Berta; Millar, Robert Peter; Zohar, Yonathan

    2015-09-01

    The importance of kisspeptin in regulating vertebrate reproduction has been well established, but the exact mechanism continues to unfold. Unlike mammals, many lower vertebrates possess a dual kisspeptin system, Kiss1 and Kiss2. To decipher the roles of the kisspeptins in fish, we identified two potential kisspeptin antagonists, pep 234 and pep 359, by screening analogs for their ability to inactivate striped bass Kiss1 and Kiss2 receptors expressed in COS7 cells. Pep 234 (a mammalian KISS1 antagonist) antagonizes Kiss1r signaling activated by Kiss1 and Kiss2, and pep 359 (a novel analog) antagonizes Kiss2 activation of both receptors. In vitro studies using brain slices demonstrated that only Kiss2 can upregulate the expression of the hypophysiotropic gnrh1, which was subsequently diminished by pep 234 and pep 359. In primary pituitary cell cultures, the two antagonists revealed a complex network of putative endogenous and exogenous regulation by kisspeptin. While both kisspeptins stimulate Fsh expression and secretion, Kiss2 predominately induces Lh secretion. Pep 234 and 359 treatment of spawning males hindered sperm production. This effect was accompanied with decreased brain gnrh1 and gnrh2 mRNA levels and peptide content in the pituitary, and increased levels of pituitary Lh, probably due to attenuation of Lh release. Strikingly, the mRNA levels of arginine-vasotocin, the neurons of which in the preoptic area coexpress kiss2r, were dramatically reduced by the antagonists. Our results demonstrate differential actions of Kiss1 and Kiss2 systems along the hypothalamic-pituitary axis and interactions with other neuropeptides, and further reinforce the importance of kisspeptin in the execution of spawning. © 2015 by the Society for the Study of Reproduction, Inc.

  14. Mapping PTGERs to the Ovulatory Follicle: Regional Responses to the Ovulatory PGE2 Signal1

    PubMed Central

    Kim, Soon Ok; Duffy, Diane M.

    2016-01-01

    Prostaglandin E2 (PGE2) is a key intrafollicular mediator of ovulation in many, if not all, mammalian species. PGE2 acts at follicular cells via four distinct PGE2 receptors (PTGERs). Within the ovulatory follicle, each cell type (e.g., oocyte, cumulus granulosa cell, mural granulosa cell, theca cell, endothelial cell) expresses a different subset of the four PTGERs. Expression of a subset of PTGERs has consequences for the generation of intracellular signals and ultimately the unique functions of follicular cells that respond to PGE2. Just as the ovulatory LH surge regulates PGE2 synthesis, the LH surge also regulates expression of the four PTGERs. The pattern of expression of the four PTGERs among follicular cells before and after the LH surge forms a spatial and temporal map of PGE2 responses. Differential PTGER expression, coupled with activation of cell-specific intracellular signals, may explain how a single paracrine mediator can have pleotropic actions within the ovulatory follicle. Understanding the role of each PTGER in ovulation may point to previously unappreciated opportunities to both promote and prevent fertility. PMID:27307073

  15. Seasonal effects of irrigation on land-atmosphere latent heat, sensible heat and carbon fluxes in semi-arid basin

    NASA Astrophysics Data System (ADS)

    Xie, Zhenghui; Zeng, Yujin

    2017-04-01

    Irrigation, which constitutes 70% of the total amount of fresh water consumed by the human population, is significantly impacting the land-atmosphere fluxes. In this study, using the improved Community Land Model version 4.5 (CLM 4.5) with an active crop model, two high resolution ( 1 km) simulations investigating the effects of irrigation on Latent Heat (LH), Sensible Heat (SH) and Carbon Fluxes (or net ecosystem exchange, NEE) from land to atmosphere on the Heihe River Basin in northwestern China were conducted using a high-quality irrigation dataset compiled from 1981 to 2013. The model output and measurements from remote sensing demonstrated the capacity and viability of the developed models to reproduce ecological and hydrological processes. The results revealed the effects of irrigation on LH and SH are strongest during summer with a LH increase of 100 W/m2 and a SH decrease of 60 W/m2 over intensely irrigated areas. However, the reactions are much weaker during spring and autumn when there is much less irrigation. When the irrigation rate below 5 mm/day, the LH generally increases, whereas the SH decreases with growing irrigation rates. However, when the irrigation threshold is in excess of 5 mm/day, there is no accrued effect of irrigation on the LH and SH. Irrigation produces opposite effects to the NEE during spring and summer. During the spring, irrigation yields more discharged carbon from the land to the atmosphere, increasing the NEE value by 0.4-0.8 gC/m2/day, while the summer irrigation favors crop fixing of carbon from atmospheric CO2, decreasing the NEE value by 0.8 gC/m2/day. The repercussions of irrigation on land-atmosphere fluxes are not solely linked to the irrigation amount, and other parameters (especially the temperature) also control the effects of irrigation on LH, SH and NEE. The study indicates that how a land surface model with high spatial resolution can represent crop growing and its effects over basin scale.

  16. The “Ram Effect”: A “Non-Classical” Mechanism for Inducing LH Surges in Sheep

    PubMed Central

    Fabre-Nys, Claude; Chanvallon, Audrey; Dupont, Joëlle; Lardic, Lionel; Lomet, Didier; Martinet, Stéphanie; Scaramuzzi, Rex J.

    2016-01-01

    During spring sheep do not normally ovulate but exposure to a ram can induce ovulation. In some ewes an LH surge is induced immediately after exposure to a ram thus raising questions about the control of this precocious LH surge. Our first aim was to determine the plasma concentrations of oestradiol (E2) E2 in anoestrous ewes before and after the “ram effect” in ewes that had a “precocious” LH surge (starting within 6 hours), a “normal” surge (between 6 and 28h) and “late» surge (not detected by 56h). In another experiment we tested if a small increase in circulating E2 could induce an LH surge in anoestrus ewes. The concentration of E2 significantly was not different at the time of ram introduction among ewes with the three types of LH surge. “Precocious” LH surges were not preceded by a large increase in E2 unlike “normal” surges and small elevations of circulating E2 alone were unable to induce LH surges. These results show that the “precocious” LH surge was not the result of E2 positive feedback. Our second aim was to test if noradrenaline (NA) is involved in the LH response to the “ram effect”. Using double labelling for Fos and tyrosine hydroxylase (TH) we showed that exposure of anoestrous ewes to a ram induced a higher density of cells positive for both in the A1 nucleus and the Locus Coeruleus complex compared to unstimulated controls. Finally, the administration by retrodialysis into the preoptic area, of NA increased the proportion of ewes with an LH response to ram odor whereas treatment with the α1 antagonist Prazosin decreased the LH pulse frequency and amplitude induced by a sexually active ram. Collectively these results suggest that in anoestrous ewes NA is involved in ram-induced LH secretion as observed in other induced ovulators. PMID:27384667

  17. An unprecedented Fe(36) phosphonate cage.

    PubMed

    Beavers, Christine M; Prosvirin, Andrey V; Prosverin, Andrey V; Cashion, John D; Dunbar, Kim R; Richards, Anne F

    2013-02-18

    The reaction of 2-pyridylphosphonic acid (LH(2)) with iron(II) perchlorate and iron(III) nitrate afforded an interconnected, double-layered, cationic iron cage, [{Fe(36)L(44)(H(2)O)(48)}](20+) (1a), the largest interconnected, polynuclear ferric cage reported to date. Magnetic studies on 1a revealed antiferromagnetic coupling between the spins on adjacent Fe(III) ions.

  18. Orbiter LH2 Feedline Flowliner Cracking Problem. Version 1.0

    NASA Technical Reports Server (NTRS)

    Harris, Charles E.; Cragg, Clinton H.; Raju, Ivatury S.; Elliot, Kenny B.; Madaras, Eric I.; Piascik, Robert S.; Halford, Gary R.; Bonacuse, Peter J.; Sutliff, Daniel L.; Bakhle, Milind A.

    2005-01-01

    In May of 2002, three cracks were found in the downstream flowliner at the gimbal joint in the LH2 feedline at the interface with the Low Pressure Fuel Turbopump (LPFP) of Space Shuttle Main Engine (SSME) #1 of Orbiter OV-104. Subsequent inspections of the feedline flowliners in the other orbiters revealed the existence of 8 additional cracks. No cracks were found in the LO2 feedline flowliners. A solution to the cracking problem was developed and implemented on all orbiters. The solution included weld repair of all detectable cracks and the polishing of all slot edges to remove manufacturing discrepancies that could initiate new cracks. Using the results of a fracture mechanics analysis with a scatter factor of 4 on the predicted fatigue life, the orbiters were cleared for return to flight with a one-flight rationale requiring inspections after each flight. OV-104 flew mission STS-112 and OV-105 flew mission STS-113. The post-flight inspections did not find any cracks in the repaired flowliners. At the request of the Orbiter Program, the NESC conducted an assessment of the Orbiter LH2 Feedline Flowliner cracking problem with a team of subject matter experts from throughout NASA.

  19. Hippocampal astrocytes are necessary for antidepressant treatment of learned helplessness rats.

    PubMed

    Iwata, Masaaki; Shirayama, Yukihiko; Ishida, Hisahito; Hazama, Gen-i; Nakagome, Kazuyuki

    2011-08-01

    The astrocyte is a major component of the neural network and plays a role in brain function. Previous studies demonstrated changes in the number of astrocytes in depression. In this study, we examined alterations in the number of astrocytes in the learned helplessness (LH) rat, an animal model of depression. The numbers of activated and nonactivated astrocytes in the dentate gyrus (molecular layer, subgranular zone, and hilus), and CA1 and CA3 regions of the hippocampus were significantly increased 2 and 8 days after attainment of LH. Subchronic treatment with imipramine showed a tendency (although not statistically significant) to decrease the LH-induced increment of activated astrocytes in the CA3 region and dentate gyrus. Furthermore, subchronic treatment of naïve rats with imipramine did not alter the numbers of activated and nonactivated astrocytes. However, the antidepressant-like effects of imipramine in the LH paradigm were blocked when fluorocitrate (a reversible inhibitor of astrocyte function) was injected into the dentate gyrus or CA3 region. Injection of fluorocitrate into naive rats failed to induce behavioral deficits in the conditioned avoidance test. These results indicate that astrocytes are responsive to the antidepressant-like effect of imipramine in the dentate gyrus and CA3 region of the hippocampus. Copyright © 2010 Wiley-Liss, Inc.

  20. Characterisation of the LH2 spectral variants produced by the photosynthetic purple sulphur bacterium Allochromatium vinosum.

    PubMed

    Carey, Anne-Marie; Hacking, Kirsty; Picken, Nichola; Honkanen, Suvi; Kelly, Sharon; Niedzwiedzki, Dariusz M; Blankenship, Robert E; Shimizu, Yuuki; Wang-Otomo, Zheng-Yu; Cogdell, Richard J

    2014-11-01

    This study systematically investigated the different types of LH2 produced by Allochromatium (Alc.) vinosum, a photosynthetic purple sulphur bacterium, in response to variations in growth conditions. Three different spectral forms of LH2 were isolated and purified, the B800-820, B800-840 and B800-850 LH2 types, all of which exhibit an unusual split 800 peak in their low temperature absorption spectra. However, it is likely that more forms are also present. Relatively more B800-820 and B800-840 are produced under low light conditions, while relatively more B800-850 is produced under high light conditions. Polypeptide compositions of the three different LH2 types were determined by a combination of HPLC and TOF/MS. The B800-820, B800-840 and B800-850 LH2 types all have a heterogeneous polypeptide composition, containing multiple types of both α and β polypeptides, and differ in their precise polypeptide composition. They all have a mixed carotenoid composition, containing carotenoids of the spirilloxanthin series. In all cases the most abundant carotenoid is rhodopin; however, there is a shift towards carotenoids with a higher conjugation number in LH2 complexes produced under low light conditions. CD spectroscopy, together with the polypeptide analysis, demonstrates that these Alc. vinosum LH2 complexes are more closely related to the LH2 complex from Phs. molischianum than they are to the LH2 complexes from Rps. acidophila. Copyright © 2014. Published by Elsevier B.V.

  1. Comparison of the effect of natural mating, LH, and GnRH on interval to ovulation and luteal function in llamas.

    PubMed

    Ratto, Marcelo; Huanca, Wilfredo; Singh, Jaswant; Adams, Gregg P

    2006-02-01

    Gonadotropins and GnRH have been used to electively induce ovulation in llamas and alpacas, but critical evaluation of the natural interval to ovulation after mating has not been performed nor has a direct comparison of the effects of natural mating versus hormone treatments on this interval and subsequent luteal development. The objectives of this study were to compare the effects of hormonal treatments and natural mating on ovulation induction, interval to ovulation, and luteal development in llamas. The ovaries of llamas were examined by transrectal ultrasonography once daily. Llamas with a large follicle were assigned randomly to be: (1) mated with an intact male (mated; n=10); (2) given 5 mg of LH im (LH; n=11); or (3) 50 microg of GnRH im (GnRH; n=10). Ultrasound examinations were performed every 4h from treatment (day 0) to ovulation and thereafter once daily for 15 consecutive days to monitor CL growth and regression (n=5 per group). Plasma progesterone concentrations were measured at days 0, 3, 6, 9, and 12 after treatment to evaluate CL function. The size of the largest preovulatory follicle at the time of treatment did not differ among groups (11+/-0.6, 10.5+/-0.8, 11.8+/-0.9 mm, for mated, LH, and GnRH groups, respectively; P=0.6). No differences were detected among groups (mated, LH, and GnRH) in ovulation rate (80%, 91%, 80%, respectively; P=0.6), or interval from treatment to ovulation (30.0+/-0.5, 29.3+/-0.6, 29.3+/-0.7h, respectively; P=0.9). Similarly, no differences were detected among groups (mated, LH, and GnRH) in maximum CL diameter (14.2+/-0.3, 13.2+/-0.5, and 13.0+/-0.7 mm, respectively; P=0.5), the day of maximum CL diameter (7.6+/-0.2, 7.6+/-0.2, and 7.4+/-0.4 mm, respectively; P=0.6), or the day on which the CL began to regress (12.3+/-0.3 [non-pregnant, n=3], 11.8+/-0.6, 12.2+/-0.4, respectively; P=0.4). The diameter of the CL and plasma progesterone concentrations changed over days (P<0.0001) but the profiles did not differ among groups. In summary, ovulation rate, interval to ovulation, and luteal development were similar among llamas that were mated naturally or treated with LH or GnRH. We conclude that both hormonal preparations are equally reliable for inducing ovulation and suitable for synchronization for artificial insemination or embryo transfer program.

  2. Evidence that obesity and androgens have independent and opposing effects on gonadotropin production from puberty to maturity

    PubMed Central

    Rosenfield, Robert L; Bordini, Brian

    2010-01-01

    Optimal fat mass is necessary for normal gonadotropin levels in adults, and both undernutrition and overnutrition suppress gonadotropins: thus, the gonadotropin response to relative adipose mass is biphasic. Adult obesity is associated with blunted luteinizing hormone (LH) pulse amplitude that is partially attributable to increased LH clearance rate. Testosterone appears to have a biphasic effect on gonadotropin production in females. Moderate elevations of testosterone appear to stimulate LH production at both the hypothalamic and pituitary level, while very high levels of testosterone suppress LH. Thus, obesity per se appears to suppress gonadotropin production, and moderate hyperandrogenemia in women appears to stimulate LH. The ordinary hypergonadotropic hyperandrogenism of obese women appears to be an exception to this model because it is usually due to polycystic ovary syndrome (PCOS), a condition in which intrinsic functional ovarian hyperandrogenism and excess adiposity share a common origin that involves insulin-resistant hyperinsulinemia. LH elevation seems to be secondary to hyperandrogenemia and is absent in the most obese cases. Overweight early pubertal girls have significant blunting of sleep-related LH production, which is the first hormonal change of puberty. The data are compatible with the possibility that excess adiposity may paradoxically subtly suppress hypothalamic-pituitary-gonadal function in early puberty although it is known to contribute to the early onset of puberty. PMID:20816944

  3. Bio-equivalent doses of recombinant HCG and recombinant LH during ovarian stimulation result in similar oestradiol output: a randomized controlled study.

    PubMed

    Alsbjerg, Birgit; Elbaek, Helle Olesen; Laursen, Rita Jakubcionyte; Povlsen, Betina Boel; Haahr, Thor; Yding Andersen, Claus; Humaidan, Peter

    2017-08-01

    In nature, HCG is secreted by the implanting embryo from peri-implantation and onwards. In contrast, LH is mandatory for steroidogenesis and follicular development during the follicular phase, working in synergy with FSH. Moreover, LH is mandatory for the function of the corpus luteum. Although LH and HCG bind to the same receptor, significant molecular, structural and functional differences exist, inducing differences in bioactivity. This randomized controlled study compared the effect of recombinant FSH stimulation combined with daily either micro-dose recombinant HCG or recombinant LH supplementation in a 1:1 bioactivity ratio from day 1 of stimulation in a long gonadotrophin releasing hormone agonist down regulation protocol. A total of 100 patients from a public clinic completed the study. The primary end-point was the oestradiol level on the day of ovulation trigger and the median oestradiol level in the HCG supplemented group was 8662 pmol/l versus 9203 pmol/l in the recombinant LH supplemented group; therefore, no significant difference was found. Moreover, no differences were observed in the number of oocytes retrieved or in the live birth rate. We conclude that recombinant HCG and recombinant LH are equally effective in boosting oestradiol synthesis during ovarian stimulation when used in a 1:1 bioactivity ratio. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  4. Asparagine-linked oligosaccharides on lutropin, follitropin, and thyrotropin: distributions of sulfated and sialylated oligosaccharides on bovine, ovine, and human pituitary glycoprotein hormones

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Green, E.D.; Baenziger, J.U.

    1988-01-05

    The asparagine-linked oligosaccharides on the pituitary glycoprotein hormones lutropin (LH), follitropin (FSH), and thyrotropin (TSH) consist of a heterogeneous array of neutral, sulfated, sialylated, and sulfated/sialylated structures. In this study, the authors determined the relative quantities of the various asparagine-linked oligosaccharides on LH, FSH, and TSH from these three animal species. The proportions of sulfated versus sialylated oligosaccharides varied markedly among the different hormones. Both hormone- and animal species-specific differences in the types and distributions of sulfated, sialylated, and sulfated/sialylated structures were evident. In particular, LH and FSH, which are synthesized in the same pituitary cell and bear ..cap alpha..-subunitsmore » with the identical amino acid sequence, contained significantly different distributions of sulfated and sialylated oligosaccharides. For all three animal species, the ratio of sialylated to sulfated oligosaccharides differed by >10-fold for LH and FSH, with sulfated structures dominating on LH and sialylated structures on FSH. Sialylated oligosaccharides were also heterogeneous with respect to sialic acid linkage (..cap alpha..2,3 versus ..cap alpha..2,6). The differences in oligosaccharide structures among the various pituitary glycoprotein hormones as well as among the various glycosylation sites within a single hormone support the hypothesis that glycosylation may serve important functional roles in the expression and/or regulation of hormone bioactivity.« less

  5. Monomeric RC-LH1 core complexes retard LH2 assembly and intracytoplasmic membrane formation in PufX-minus mutants of Rhodobacter sphaeroides

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Adams, Peter G.; Mothersole, David J.; Ng, Irene W.

    2011-01-01

    In the model photosynthetic bacterium Rhodobacter sphaeroides domains of light-harvesting 2 (LH2) complexes surround and interconnect dimeric reaction centre–light-harvesting 1–PufX (RC–LH1–PufX) ‘core’ complexes, forming extensive networks for energy transfer and trapping. These complexes are housed in spherical intracytoplasmic membranes (ICMs), which are assembled in a stepwise process where biosynthesis of core complexes tends to dominate the early stages of membrane invagination. The kinetics of LH2 assembly were measured in PufX mutants that assemble monomeric core complexes, as a consequence of either a twelve-residue N-terminal truncation of PufX (PufXΔ12) or the complete removal of PufX (PufX -). Lower rates of LH2more » assembly and retarded maturation of membrane invagination were observed for the larger and less curved ICM from the PufX - mutant, consistent with the proposition that local membrane curvature, initiated by arrays of bent RC–LH1–PufX dimers, creates a favourable environment for stable assembly of LH2 complexes. Transmission electron microscopy and high-resolution atomic force microscopy were used to examine ICM morphology and membrane protein organisation in these mutants. Some partitioning of core and LH2 complexes was observed in PufX - membranes, resulting in locally ordered clusters of monomeric RC–LH1 complexes. The distribution of core and LH2 complexes in the three types of membrane examined is consistent with previous models of membrane curvature and domain formation (Frese et al., 2008), which demonstrated that a combination of crowding and asymmetries in sizes and shapes of membrane protein complexes drives membrane organisation.« less

  6. Monomeric RC-LH1 core complexes retard LH2 assembly and intracytoplasmic membrane formation in PufX-minus mutants of Rhodobacter sphaeroides.

    PubMed

    Adams, Peter G; Mothersole, David J; Ng, Irene W; Olsen, John D; Hunter, C Neil

    2011-09-01

    In the model photosynthetic bacterium Rhodobacter sphaeroides domains of light-harvesting 2 (LH2) complexes surround and interconnect dimeric reaction centre-light-harvesting 1-PufX (RC-LH1-PufX) 'core' complexes, forming extensive networks for energy transfer and trapping. These complexes are housed in spherical intracytoplasmic membranes (ICMs), which are assembled in a stepwise process where biosynthesis of core complexes tends to dominate the early stages of membrane invagination. The kinetics of LH2 assembly were measured in PufX mutants that assemble monomeric core complexes, as a consequence of either a twelve-residue N-terminal truncation of PufX (PufXΔ12) or the complete removal of PufX (PufX(-)). Lower rates of LH2 assembly and retarded maturation of membrane invagination were observed for the larger and less curved ICM from the PufX(-) mutant, consistent with the proposition that local membrane curvature, initiated by arrays of bent RC-LH1-PufX dimers, creates a favourable environment for stable assembly of LH2 complexes. Transmission electron microscopy and high-resolution atomic force microscopy were used to examine ICM morphology and membrane protein organisation in these mutants. Some partitioning of core and LH2 complexes was observed in PufX(-) membranes, resulting in locally ordered clusters of monomeric RC-LH1 complexes. The distribution of core and LH2 complexes in the three types of membrane examined is consistent with previous models of membrane curvature and domain formation (Frese et al., 2008), which demonstrated that a combination of crowding and asymmetries in sizes and shapes of membrane protein complexes drives membrane organisation. 2011 Elsevier B.V. All rights reserved.

  7. Occurrence of primary lymphocytic hypophysitis in two horses and presence of scattered T-lymphocytes in the normal equine pituitary gland.

    PubMed

    Grau-Roma, Llorenç; Peckham, Robert; Paton, Jacqui; Stahel, Anina; de Brot, Simone

    2017-01-01

    The postmortem examination of a 14-y-old Appaloosa gelding with clinically diagnosed pituitary pars intermedia dysfunction showed a unique finding of moderate multifocal lymphocytic hypophysitis (LH). The pituitary glands of 24 horses submitted for postmortem examination were examined grossly and examined histologically for the presence of lymphocytes. Of these 23 horses, 1 additional case suffered from moderate LH. The 2 cases with LH tested negative for Equid herpesvirus 1 and 4 by polymerase chain reaction and immunohistochemistry (IHC), and no viral particles were observed by electron microscopy in 1 case examined. The cause of LH remains unknown, but based on the T-lymphocytic nature of the inflammation and the human literature, an immune-mediated origin is hypothesized. In addition, the review of 24 cases revealed that 10 horses had few and small multifocal lymphocytic infiltrates within the pituitary gland; the remaining 12 horses showed no evident lymphocytes when examined by hematoxylin and eosin. IHC for CD3 showed the presence of a small number of individual T-lymphocytes scattered through the gland in all examined horses, which appears therefore to be a normal feature of the pituitary gland in horses.

  8. Protective effects of D-Trp6-luteinising hormone-releasing hormone microcapsules against cyclophosphamide-induced gonadotoxicity in female rats.

    PubMed Central

    Bokser, L.; Szende, B.; Schally, A. V.

    1990-01-01

    The possible protective effect of an agonist of luteinising hormone-releasing hormone (LH-RH) against the ovarian damage caused by cyclophosphamide was investigated in rats. D-Trp6-LH-RH microcapsules were injected once a month for 3 months, in a dose calculated to release 25 micrograms day-1. Control animals received the injection vehicle. Sixty days after the first injection of microcapsules, cyclophosphamide was given at a loading dose of 50 mg kg-1 followed by 5 mg kg-1 day-1 for 30 days, while the treatment with D-Trp6-LH-RH was continued. When the ovaries were examined 3 months and 5 months after discontinuation of treatment, a significant reduction in the total number of follicles (P less than 0.01) was found in non-pretreated animals given cyclophosphamide. This reduction affected mainly follicles larger than 100 microns. An irreversible disintegration and destruction of granulosa cells was also observed in this group. In animals pretreated with D-Trp6-LH-RH, administration of cyclophosphamide caused no reduction in the number and diameter of follicles. Thus, the treatment with D-Trp6-LH-RH microcapsules before and during chemotherapy prevented the ovarian injury inflicted by cyclophosphamide. The suppression of gonadal function by LH-RH analogues could be possibly utilised for the protection of the ovaries against damage caused by cytotoxic drugs. Images Figure 2 PMID:2142603

  9. 14 CFR Appendix E to Part 420 - Tables for Explosive Site Plan

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    .... Table E-2—Liquid Propellant Explosive Equivalents Propellant combinations Explosive equivalent LO2/LH2 The larger of: 8W2/3 where W is the weight of LO2/LH2, or14% of W. LO2/LH2 + LO2/RP-1 Sum of (20% for LO2/RP-1) + the larger of: 8W2/3 where W is the weight of LO2/LH2, or14% of W. LO2/R-1 20% of W up to...

  10. Evaluation of learned helplessness, self-efficacy and disease activity, functional capacity and pain in Argentinian patients with rheumatoid arthritis.

    PubMed

    Vergara, F; Rosa, J; Orozco, C; Bertiller, E; Gallardo, M A; Bravo, M; Catay, E; Collado, V; Gómez, G; Sabelli, M; García, M V; Rosemffet, M G; Citera, G; Schneeberger, E E; Catoggio, L J; Soriano, E R

    2017-01-01

    To evaluate the association between learned helplessness (LH) and self-efficacy (SE) with disease activity, functional capacity, and level of pain in patients with rheumatoid arthritis (RA) and to compare LH and SE between patients in remission and patients with active disease. This multicentre, cross-sectional study included consecutive patients (aged ≥ 18 years) with RA according to 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria. LH was measured by the Rheumatology Attitude Index (RAI), Spanish version; SE with the Arthritis Self-efficacy Scale (ASES), Spanish version; functional capacity with the Health Assessment Questionnaire, Argentinian version (HAQ-A); and perceived pain by the visual analogue scale (VAS). Disease activity was measured by the Clinical Disease Activity Index (CDAI). A total of 115 patients (82% females) with a mean (± sd) age of 58 ± 13 years were included. We found a significantly positive correlation between LH and perceived pain (p < 0.001), HAQ-A score (p < 0.001), and CDAI (p < 0.001) and a significantly negative correlation between SE and perceived pain (p < 0.001), HAQ-A score (p < 0.001), and CDAI (p < 0.001). We found greater levels of SE and lower grades of LH in patients in remission compared to those with active disease (median 76 vs. 58; p < 0.001 and 6 vs. 11; p < 0.001, respectively). LH and SE correlated significantly with disease activity, functional capacity, and perceived pain. Levels of SE were higher in patients in remission compared to those with active disease as opposed to levels of LH, which were lower in patients in remission compared to those with active disease. These results show that cognitive factors are related to disease activity and their modifications may have importance in the management of RA.

  11. Down-regulation of pituitary receptors for luteinizing hormone-releasing hormone (LH-RH) in rats by LH-RH antagonist Cetrorelix.

    PubMed Central

    Halmos, G; Schally, A V; Pinski, J; Vadillo-Buenfil, M; Groot, K

    1996-01-01

    Antagonists of luteinizing hormone-releasing hormone (LH-RH), unlike the LH-RH agonists, suppress gonadotropins and sex steroid secretion immediately after administration, without initial stimulatory effects. [Ac-D-Nal(2)1,D-Ph(4Cl)2,D-Pal(3)3,D-Cit6,D-Ala10]LH-R H (SB-75; Cetrorelix) is a modern, potent antagonistic analog of LH-RH. In this study, the binding characteristics of receptors for LH-RH in membrane fractions from rat anterior pituitaries were investigated after a single injection of Cetrorelix at a dose of 100 microg per rat. To determine whether the treatment with Cetrorelix can affect the concentration of measurable LH-RH binding sites, we applied an in vitro method to desaturate LH-RH receptors by chaotropic agents such as manganous chloride (MnCl2) and ammonium thiocyanate (NH4SCN). Our results show that the percentages of occupied LH-RH receptors at 1, 3, and 6 h after administration of Cetrorelix were approximately 28%, 14%, and 10%, respectively, of total receptors. At later time intervals, we could not detect occupied LH-RH binding sites. Ligand competition assays, following in vitro desaturation, demonstrated that rat pituitary LH-RH receptors were significantly (P < 0.01) down-regulated for at least 72 h after administration of Cetrorelix. The lowest receptor concentration was found 3-6 h after Cetrorelix treatment and a recovery in receptor number began within approximately 24 h. The down-regulation of LH-RH binding sites induced by Cetrorelix was accompanied by serum LH and testosterone suppression. Higher LH-RH receptor concentrations coincided with elevated serum hormone levels at later time intervals. Our results indicate that administration of LH-RH antagonist Cetrorelix produces a marked down-regulation of pituitary receptors for LH-RH and not merely an occupancy of binding sites. PMID:8637885

  12. [Patients with functional hypothalamic amenorrhea are characterized by low serum inhibin B concentrations].

    PubMed

    Podfigurna-Stopa, Agnieszka; Luisi, Stefano; Lazzeri, Lucia; Ciani, Valentina; Meczekalski, Błazej; Petraglia, Felice

    2010-05-01

    Functional hypothalamic disturbances may be the cause of secondary amenorrhea and are related to aberration in both the pattern of pulsatility and amplitude in the release of gonadotropin-releasing hormone (GnRH) in hypothalamus. Inhibin B, as an ovarian peptide plays a crucial role in reproduction function throughout regulation of folliculotropin (FSH) pituitary production and inhibiting GnRH secretion during the menstrual cycle. To measure and estimate serum inhibin B concentration in patients with functional hypothalamic amenorrhea. Material and methods. The study included 41 women suffering from functional hypothalamic amenorrhea. Secondary amenorrhea was defined as the lack of menstruation lasting at least 90 days not due to pregnancy, characterized by low serum concentrations of lutropin (LH < 5 mIU/ml)) and typical for functional hypothalamic disturbances anamnestic investigation. The control group consists of 40 healthy women with normal menstrual cycles and Body Mass Index (BMI between 18.5- 24.9 kg/m2). Medical history, examination and laboratory analysis of LH, FSH, estradiol (E), prolactin, testosterone and inhibin B were performed (ELISA--enzyme-linked immunosorbent assay). There are statistically lower serum inhibin B, FSH, LH, estradiol and prolactin concentrations in patients with functional hypothalamic amenorrhea in comparison to healthy women. Positive correlation between serum concentration of inhibin B and estradiol concentration was found in patients with functional hypothalamic amenorrhea. Patients with functional hypothalamic amenorrhea are characterized by statistical significant decrease in serum inhibin B concentration in comparison to the control group.

  13. Valproic acid improves the tolerance for the stress in learned helplessness rats.

    PubMed

    Kobayashi, H; Iwata, M; Mitani, H; Yamada, T; Nakagome, K; Kaneko, K

    2012-04-01

    In this study, we investigated whether previously stressed rats with learned helplessness (LH) paradigm could recover from depressive-like behavior four weeks after the exposure, and also whether chronic treatment with valproic acid (VPA) could prevent behavioral despair due to the second stress on days 54 in these animals. Four weeks after induction of LH, we confirmed behavioral remission in the previously stressed rats. Two-way analysis of variance (ANOVA) performed with two factors, pretreatment (LH or Control) and drug (VPA or Saline), revealed a significant main effect of the drug on immobility time in forced swimming test. Post hoc test showed a shorter immobility time in the LH+VPA group than in the LH+Saline group. Immunohistochemical study of synapsin I showed a significant effect of drug by pretreatment interaction on immunoreactivity of synapsin I in the hippocampus: its expression levels in the regions were higher in the LH+VPA group than in the LH+Saline group. These results suggest that VPA could prevent the reappearance of stress-induced depressive-like behaviors in the rats recovering from prior stress, and that the drug-induced presynaptic changes in the expression of synapsin I in the hippocampus of LH animals might be related to improved tolerance toward the stress. Copyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  14. Prenatal exposure to ethanol stimulates hypothalamic CCR2 chemokine receptor system: Possible relation to increased density of orexigenic peptide neurons and ethanol drinking in adolescent offspring

    PubMed Central

    Chang, G.-Q.; Karatayev, O.; Leibowitz, S. F.

    2015-01-01

    Clinical and animal studies indicate that maternal consumption of ethanol during pregnancy increases alcohol drinking in the offspring. Possible underlying mechanisms may involve orexigenic peptides, which are stimulated by prenatal ethanol exposure and themselves promote drinking. Building on evidence that ethanol stimulates neuroimmune factors such as the chemokine CCL2 that in adult rats is shown to colocalize with the orexigenic peptide, melanin-concentrating hormone (MCH) in the lateral hypothalamus (LH), the present study sought to investigate the possibility that CCL2 or its receptor CCR2 in LH are stimulated by prenatal ethanol exposure, perhaps specifically within MCH neurons. Our paradigm of intraoral administration of ethanol to pregnant rats, at low-to-moderate doses (1 or 3 g/kg/day) during peak hypothalamic neurogenesis, caused in adolescent male offspring two-fold increase in drinking of and preference for ethanol and reinstatement of ethanol drinking in a two-bottle choice paradigm under an intermittent access schedule. This effect of prenatal ethanol exposure was associated with an increased expression of MCH and density of MCH+ neurons in LH of preadolescent offspring. Whereas CCL2+ cells at this age were low in density and unaffected by ethanol, CCR2+ cells were dense in LH and increased by prenatal ethanol, with a large percentage (83–87%) identified as neurons and found to colocalize MCH. Prenatal ethanol also stimulated the genesis of CCR2+ and MCH+ neurons in the embryo, which co-labeled the proliferation marker, BrdU. Ethanol also increased the genesis and density of neurons that co-expressed CCR2 and MCH in LH, with triple-labeled CCR2+/MCH+/BrdU+ neurons that were absent in control rats accounting for 35% of newly generated neurons in ethanol-exposed rats. With both the chemokine and MCH systems believed to promote ethanol consumption, this greater density of CCR2+/MCH+ neurons in the LH of preadolescent rats suggests that these systems function together in promoting alcohol drinking during adolescence. PMID:26365610

  15. Overview of LH experiments in JET with an ITER-like wall

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kirov, K. K.; Baranov, Yu.; Brix, M.

    2014-02-12

    An overview of the recent results of Lower Hybrid (LH) experiments at JET with the ITER-like wall (ILW) is presented. Topics relevant to LH wave coupling are addressed as well as issues related to ILW and LH system protections. LH wave coupling was studied in conditions determined by ILW recycling and operational constraints. It was concluded that LH wave coupling was not significantly affected and the pre-ILW performance could be recovered after optimising the launcher position and local gas puffing. SOL density measurements were performed using a Li-beam diagnostic. Dependencies on the D2 injection rate from the dedicated gas valve,more » the LH power and the LH launcher position were analysed. SOL density modifications due to LH were modelled by the EDGE2D code assuming SOL heating by collisional dissipation of the LH wave and/or possible ExB drifts in the SOL. The simulations matched reasonably well the measured SOL profiles. Observations of arcs and hotspots with visible and IR cameras viewing the LH launcher are presented.« less

  16. Social Status and Social Perceptual Abilities of Mildly Handicapped Learners: Methodological and Substantive Implications.

    ERIC Educational Resources Information Center

    Morrison, Gale M.

    In an examination of the notion of person-environment fit as it applies to the socioempathy-social status for mildly handicapped children in mainstreamed and special class settings, 38 mildly learning handicapped (LH) and 234 nonhandicapped students were administered social status instruments. Results revealed that LH Ss in special placements were…

  17. Hyperestrogenemia and presence of estrogen receptors associated with an epithelial ovarian tumor of low malignant potential.

    PubMed

    Ben-Hur, H; Dgani, R; Insler, V; Lifschitz-Mercer, B; Blickstein, I; Mor, G; Kohen, F; Shani, A; Biran, H

    1996-01-01

    An 80-year-old woman presented with breast congestion, tenderness and pain. Mammography was normal. Circulating estradiol was markedly elevated, while LH and FSH were low. Pelvic examination and imaging revealed an ovarian mass which was extirpated during total abdominal hysterectomy and bilateral salpingo-oophorectomy. Histopathology revealed an ovarian mucinous cystadenocarcinoma of low malignant potential, stage 1. The tumor was positively stained for estrogen receptors. Estradiol levels returned to normal post-operatively, with a corresponding adjustment of LH/FSH. Possible autocrine steroid production is discussed.

  18. hCG: Biological Functions and Clinical Applications

    PubMed Central

    Nwabuobi, Chinedu; Arlier, Sefa; Schatz, Frederick; Guzeloglu-Kayisli, Ozlem; Lockwood, Charles Joseph; Kayisli, Umit Ali

    2017-01-01

    Human chorionic gonadotropin (hCG) is produced primarily by differentiated syncytiotrophoblasts, and represents a key embryonic signal that is essential for the maintenance of pregnancy. hCG can activate various signaling cascades including mothers against decapentaplegic homolog 2 (Smad2), protein kinase C (PKC), and/or protein kinase A (PKA) in several cells types by binding to luteinizing hormone/chorionic gonadotropin receptor (LHCGR) or potentially by direct/indirect interaction with transforming growth factor beta receptor (TGFβR). The molecule displays specialized roles in promoting angiogenesis in the uterine endothelium, maintaining myometrial quiescence, as well as fostering immunomodulation at the maternal-fetal interface. It is a member of the glycoprotein hormone family that includes luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and follicle-stimulating hormone (FSH). The α-subunit of hCG displays homologies with TSH, LH, and FSH, whereas the β subunit is 80–85% homologous to LH. The hCG molecule is produced by a variety of organs, exists in various forms, exerts vital biological functions, and has various clinical roles ranging from diagnosis and monitoring of pregnancy and pregnancy-related disorders to cancer surveillance. This review presents a detailed examination of hCG and its various clinical applications. PMID:28937611

  19. hCG: Biological Functions and Clinical Applications.

    PubMed

    Nwabuobi, Chinedu; Arlier, Sefa; Schatz, Frederick; Guzeloglu-Kayisli, Ozlem; Lockwood, Charles Joseph; Kayisli, Umit Ali

    2017-09-22

    Human chorionic gonadotropin (hCG) is produced primarily by differentiated syncytiotrophoblasts, and represents a key embryonic signal that is essential for the maintenance of pregnancy. hCG can activate various signaling cascades including mothers against decapentaplegic homolog 2 (Smad2), protein kinase C (PKC), and/or protein kinase A (PKA) in several cells types by binding to luteinizing hormone/chorionic gonadotropin receptor (LHCGR) or potentially by direct/indirect interaction with transforming growth factor beta receptor (TGFβR). The molecule displays specialized roles in promoting angiogenesis in the uterine endothelium, maintaining myometrial quiescence, as well as fostering immunomodulation at the maternal-fetal interface. It is a member of the glycoprotein hormone family that includes luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and follicle-stimulating hormone (FSH). The α-subunit of hCG displays homologies with TSH, LH, and FSH, whereas the β subunit is 80-85% homologous to LH. The hCG molecule is produced by a variety of organs, exists in various forms, exerts vital biological functions, and has various clinical roles ranging from diagnosis and monitoring of pregnancy and pregnancy-related disorders to cancer surveillance. This review presents a detailed examination of hCG and its various clinical applications.

  20. Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea, but chronic administration causes tachyphylaxis.

    PubMed

    Jayasena, Channa N; Nijher, Gurjinder M K; Chaudhri, Owais B; Murphy, Kevin G; Ranger, Amita; Lim, Adrian; Patel, Daksha; Mehta, Amrish; Todd, Catriona; Ramachandran, Radha; Salem, Victoria; Stamp, Gordon W; Donaldson, Mandy; Ghatei, Mohammad A; Bloom, Stephen R; Dhillo, Waljit S

    2009-11-01

    Kisspeptin is a critical regulator of normal reproductive function. A single injection of kisspeptin in healthy human volunteers potently stimulates gonadotropin release. However, the effects of kisspeptin on gonadotropin release in women with hypothalamic amenorrhea (HA) and the effects of repeated administration of kisspeptin to humans are unknown. The aim of this study was to determine the effects of acute and chronic kisspeptin administration on gonadotropin release in women with HA. We performed a prospective, randomized, double-blinded, parallel design study. Women with HA received twice-daily sc injections of kisspeptin (6.4 nmol/kg) or 0.9% saline (n = 5 per group) for 2 wk. Changes in serum gonadotropin and estradiol levels, LH pulsatility, and ultrasound measurements of reproductive activity were assessed. On the first injection day, potent increases in serum LH and FSH were observed after sc kisspeptin injection in women with HA (mean maximal increment from baseline within 4 h after injection: LH, 24.0 +/- 3.5 IU/liter; FSH, 9.1 +/- 2.5 IU/liter). These responses were significantly reduced on the 14th injection day (mean maximal increment from baseline within 4 h postinjection: LH, 2.5 +/- 2.2 IU/liter, P < 0.05; FSH, 0.5 +/- 0.5 IU/liter, P < 0.05). Subjects remained responsive to GnRH after kisspeptin treatment. No significant changes in LH pulsatility or ultrasound measurements of reproductive activity were observed. Acute administration of kisspeptin to women with infertility due to HA potently stimulates gonadotropin release, but chronic administration of kisspeptin results in desensitization to its effects on gonadotropin release. These data have important implications for the development of kisspeptin as a novel therapy for reproductive disorders in humans.

  1. Developmental programming: Impact of prenatal exposure to bisphenol-A and methoxychlor on steroid feedbacks in sheep

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Abi Salloum, Bachir; Steckler, Teresa L.; Herkimer, Carol

    Bisphenol-A (BPA), a polymer used in plastics manufacturing, and methoxychlor (MXC), a pesticide, are endocrine disrupting compounds with estrogenic and anti-androgenic properties. Prenatal BPA or MXC treatment induces reproductive defects in sheep with BPA causing prepubertal luteinizing hormone (LH) hypersecretion and dampening of periovulatory LH surges and MXC lengthening follicular phase and delaying the LH surge. In this study, we addressed the underlying neuroendocrine defects by testing the following hypotheses: 1) prenatal BPA, but not MXC reduces sensitivity to estradiol and progesterone negative feedback, 2) prenatal BPA, but not MXC increases pituitary responsiveness to gonadotropin releasing hormone (GnRH), and 3)more » prenatal BPA dampens LH surge response to estradiol positive feedback challenge while prenatal MXC delays the timing of the LH surge. Pregnant sheep were treated with either 1) 5 mg/kg/day BPA (produces approximately twice the level found in human circulation, n = 8), 2) 5 mg/kg/day MXC (the lowest observed effect level stated in the EPA National Toxicology Program's Report; n = 6), or 3) vehicle (cotton seed oil: C: n = 6) from days 30 to 90 of gestation. Female offspring of these ewes were ovariectomized at 21 months of age and tested for progesterone negative, estradiol negative, estradiol positive feedback sensitivities and pituitary responsiveness to GnRH. Results revealed that sensitivity to all 3 feedbacks as well as pituitary responsiveness to GnRH were not altered by either of the prenatal treatments. These findings suggest that the postpubertal reproductive defects seen in these animals may have stemmed from ovarian defects and the steroidal signals emanating from them. - Highlights: ► Prenatal BPA/MXC does not affect reproductive neuroendocrine steroid feedbacks. ► Prenatal BPA or MXC treatment failed to alter pituitary sensitivity to GnRH. ► LH excess in BPA-treated sheep may be due to reduced ovarian feedback signals.« less

  2. Sequencing and generation of an infectious clone of the pathogenic goose parvovirus strain LH.

    PubMed

    Wang, Jianye; Duan, Jinkun; Zhu, Liqian; Jiang, Zhiwei; Zhu, Guoqiang

    2015-03-01

    In this study, the complete genome of the virulent strain LH of goose parvovirus (GPV) was sequenced and cloned into the pBluescript II (SK) plasmid vector. Sequence alignments of the inverted terminal repeats (ITR) of GPV strains revealed a common 14-nt-pair deletion in the stem of the palindromic structure in the LH strain and three other strains isolated after 1982 when compared to three GPV strains isolated earlier than that time. Transfection of 11-day-old embryonated goose eggs with the plasmid pLH, which contains the entire genome of strain LH, resulted in successful rescue of the infectious virus. Death of embryos after transfection via the chorioallantoic membrane infiltration route occurred earlier than when transfection was done via the allantoic cavity inoculation route. The rescued virus exhibited virulence similar to that of its parental virus, as evaluated by the mortality rate in goslings. Generation of the pathogenic infectious clone provides us with a powerful tool to elucidate the molecular pathogenesis of GPV in the future.

  3. Evaluation of irregular menses in perimenarcheal girls: a pilot study.

    PubMed

    Browner-Elhanan, Karen J; Epstein, Jonathan; Alderman, Elizabeth M

    2003-12-01

    Acyclic vaginal bleeding in girls within three years of menarche is most commonly attributed to an immature hypothalamic-pituitary-ovarian axis. Assuming this diagnosis may preclude the practitioner from performing more definitive studies and thereby diagnosing other, treatable causes of menstrual irregularities. A retrospective chart review of 178 girls presenting to an inner-city hospital-based adolescent clinic within three years of menarche was performed. Personal and family medical and menarcheal history was assessed, and findings on physical and laboratory examination performed were evaluated. Of the 178 girls still perimenarcheal at presentation, 47 were the focus of this study. Of these, 39 had no significant findings on physical examination, while 3 had signs of functional ovarian hyperandrogenism (FOH) including obesity, hirsutism, and moderate acne with corresponding LH/FSH ratios>3, although pelvic ultrasound examination revealed normal ovaries. Four of the 39 patients with normal physical exams had LH/FSH testing done, and 1 of the 4 had an abnormal LH/FSH ratio, indicating possible FOH. Two of the 47 patients were pregnant. Other laboratory abnormalities included microcytic, hypochromic anemia in patients, and an elevated Erythrocyte Sedimentation Rate in a patient later diagnosed with a rheumatologic disorder. Those perimenarcheal girls presenting with irregular menses and findings including obesity, acne, or pallor, were likely to have treatable causes of menstrual irregularities. In one of the four girls with a normal physical examination, hormonal testing indicated possible FOH, thus suggesting that hormonal evaluation of perimenarcheal girls with menstrual irregularities may be justified, as it may reveal previously unsuspected pathology.

  4. Differences in Signal Activation by LH and hCG are Mediated by the LH/CG Receptor’s Extracellular Hinge Region

    PubMed Central

    Grzesik, Paul; Kreuchwig, Annika; Rutz, Claudia; Furkert, Jens; Wiesner, Burkhard; Schuelein, Ralf; Kleinau, Gunnar; Gromoll, Joerg; Krause, Gerd

    2015-01-01

    The human lutropin (hLH)/choriogonadotropin (hCG) receptor (LHCGR) can be activated by binding two slightly different gonadotropic glycoprotein hormones, choriogonadotropin (CG) – secreted by the placenta, and lutropin (LH) – produced by the pituitary. They induce different signaling profiles at the LHCGR. This cannot be explained by binding to the receptor’s leucine-rich-repeat domain (LRRD), as this binding is similar for the two hormones. We therefore speculate that there are previously unknown differences in the hormone/receptor interaction at the extracellular hinge region, which might help to understand functional differences between the two hormones. We have therefore performed a detailed study of the binding and action of LH and CG at the LHCGR hinge region. We focused on a primate-specific additional exon in the hinge region, which is located between LRRD and the serpentine domain. The segment of the hinge region encoded by exon10 was previously reported to be only relevant to hLH signaling, as the exon10-deletion receptor exhibits decreased hLH signaling, but unchanged hCG signaling. We designed an advanced homology model of the hormone/LHCGR complex, followed by experimental characterization of relevant fragments in the hinge region. In addition, we examined predictions of a helical exon10-encoded conformation by block-wise polyalanine (helix supporting) mutations. These helix preserving modifications showed no effect on hormone-induced signaling. However, introduction of a structure-disturbing double-proline mutant LHCGR-Q303P/E305P within the exon10-helix has, in contrast to exon10-deletion, no impact on hLH, but only on hCG signaling. This opposite effect on signaling by hLH and hCG can be explained by distinct sites of hormone interaction in the hinge region. In conclusion, our analysis provides details of the differences between hLH- and hCG-induced signaling that are mainly determined in the L2-beta loop of the hormones and in the hinge region of the receptor. PMID:26441830

  5. A review of luteinising hormone and human chorionic gonadotropin when used in assisted reproductive technology.

    PubMed

    Ezcurra, Diego; Humaidan, Peter

    2014-10-03

    Gonadotropins extracted from the urine of post-menopausal women have traditionally been used to stimulate folliculogenesis in the treatment of infertility and in assisted reproductive technology (ART). Products, such as human menopausal gonadotropin (hMG), consist not only of a mixture of the hormones, follicle-stimulating hormone (FSH), luteinising hormone (LH) and human chorionic gonadotropin (hCG), but also other biologically active contaminants, such as growth factors, binding proteins and prion proteins. The actual amount of molecular LH in hMG preparations varies considerably due to the purification process, thus hCG, mimicking LH action, is added to standardise the product. However, unlike LH, hCG plays a different role during the natural human menstrual cycle. It is secreted by the embryo and placenta, and its main role is to support implantation and pregnancy. More recently, recombinant gonadotropins (r-hFSH and r-hLH) have become available for ART therapies. Recombinant LH contains only LH molecules. In the field of reproduction there has been controversy in recent years over whether r-hLH or hCG should be used for ART. This review examines the existing evidence for molecular and functional differences between LH and hCG and assesses the clinical implications of hCG-supplemented urinary therapy compared with recombinant therapies used for ART.

  6. Cloning and Expression of β-Defensin from Soiny Mullet (Liza haematocheila), with Insights of its Antibacterial Mechanism

    PubMed Central

    Qi, Zhitao; Xu, Wei; Meng, Fancui; Zhang, Qihuan; Chen, Chenglung; Shao, Rong

    2016-01-01

    Beta-defensins are important part of innate immunity of fish, which are the first defense line against invading pathogens. In this study, the β-defensin (Lhβ-defensin) gene was cloned from spleen tissue of soiny mullet (Liza haematocheila). Lhβ-defensin cDNA was 747 bp in length, encoding 63 amino acids. Sequence alignment revealed that Lhβ-defensin contained six conserved cysteine residues and shared 97.5% sequence identities with grouper (Epinephelus coioides) β-defensin. Realtime PCR revealed that Lhβ-defensin was highest expressed in the immune related organs, such as spleen, kidney and gut of healthy fish. Following Streptococcus dysgalactiae infection, Lhβ-defensin was up-regulated in immune related organs, e.g. 17.6-fold in spleen and 10.87-fold in gut at 24 h post infection (hpi). Lhβ-defensin possessed a monomeric structure of a three-stranded anti-parallel β-sheet and an α-helix stabilized by three disulfide bonds formed by Cys30-Cys58, Cys36-Cys52, and Cys40-Cys59. In addition to the experimental work, computer simulation was also carried out to determine the possible conformation of β-defensin and its interaction with palmitoyloleoylphosphatidylglycerol (POPG), a model of bacteria membrane. The Lhβ-defensin was found to form dimeric structure stabilized by the van der Waals contacts of Leu35 and Cys37 in two anti-parallel β1-strands and the cation-π interaction between Tyr32 and Arg54 respectively in the two β1-strands. The most important interactions between β-defensin and membrane are the electrostatic interactions between Arg residues in β-defensin and head group of POPG bilayer as well as hydrogen bond interactions between them. Our results were useful for further understanding the potential mechanism of antimicrobial property of fish β-defensins. PMID:27322675

  7. Neuroendocrine abnormalities in hypothalamic amenorrhea: spectrum, stability, and response to neurotransmitter modulation.

    PubMed

    Perkins, R B; Hall, J E; Martin, K A

    1999-06-01

    To characterize the neuroendocrine patterns of abnormal GnRH secretion in hypothalamic amenorrhea (HA), 49 women with primary and secondary HA underwent frequent sampling of LH in a total of 72 baseline studies over 12-24 h. A subset of women participated in more than one study to address 1) the variability of LH pulse patterns over time; and 2) the impact of modulating opioid, dopaminergic, and adrenergic tone on LH secretory patterns. The frequency and amplitude of LH secretion was compared with that seen in the early follicular phase (EFP) of normally cycling women. The spectrum of abnormalities of LH pulses was 8% apulsatile, 27% low frequency/low amplitude, 8% low amplitude/normal frequency, 43% low frequency/normal amplitude, 14% normal frequency/normal amplitude. Of patients studied overnight, 45% demonstrated a pubertal pattern of augmented LH secretion during sleep. Of patients studied repeatedly, 75% demonstrated at least 2 different patterns of LH secretion, and 33% reverted at least once to a normal pattern of secretion. An increase in LH pulse frequency was seen in 12 of 15 subjects in response to naloxone (opioid receptor antagonist). Clonidine (alpha-2 adrenergic agonist) was associated with a decrease in mean LH in 3 of 3 subjects. An increase in LH pulse frequency was seen in 4 of 8 subjects in response to metoclopramide (dopamine receptor antagonist), but the response was not statistically significant. Baseline abnormalities in LH secretion did not appear to influence response to neurotransmitter modulation. 1) HA represents a spectrum of disordered GnRH secretion that can vary over time; 2) LH pulse patterns at baseline do not appear to influence the ability to respond to neurotransmitter modulation; 3) Opioid and adrenergic tone appear to influence the hypothalamic GnRH pulse generator in some individuals with HA.

  8. The effects of protein crowding in bacterial photosynthetic membranes on the flow of quinone redox species between the photochemical reaction center and the ubiquinol-cytochrome c2 oxidoreductase.

    PubMed

    Woronowicz, Kamil; Sha, Daniel; Frese, Raoul N; Sturgis, James N; Nanda, Vikas; Niederman, Robert A

    2011-08-01

    Atomic force microscopy (AFM) of the native architecture of the intracytoplasmic membrane (ICM) of a variety of species of purple photosynthetic bacteria, obtained at submolecular resolution, shows a tightly packed arrangement of light harvesting (LH) and reaction center (RC) complexes. Since there are no unattributed structures or gaps with space sufficient for the cytochrome bc(1) or ATPase complexes, they are localized in membrane domains distinct from the flat regions imaged by AFM. This has generated a renewed interest in possible long-range pathways for lateral diffusion of UQ redox species that functionally link the RC and the bc(1) complexes. Recent proposals to account for UQ flow in the membrane bilayer are reviewed, along with new experimental evidence provided from an analysis of intrinsic near-IR fluorescence emission that has served to test these hypotheses. The results suggest that different mechanism of UQ flow exist between species such as Rhodobacter sphaeroides, with a highly organized arrangement of LH and RC complexes and fast RC electron transfer turnover, and Phaeospirillum molischianum with a more random organization and slower RC turnover. It is concluded that packing density of the peripheral LH2 antenna in the Rba. sphaeroides ICM imposes constraints that significantly slow the diffusion of UQ redox species between the RC and cytochrome bc(1) complex, while in Phs. molischianum, the crowding of the ICM with LH3 has little effect upon UQ diffusion. This supports the proposal that in this type of ICM, a network of RC-LH1 core complexes observed in AFM provides a pathway for long-range quinone diffusion that is unaffected by differences in LH complex composition or organization.

  9. Triple X syndrome and puberty: focus on the hypothalamus-hypophysis-gonad axis.

    PubMed

    Stagi, Stefano; di Tommaso, Mariarosaria; Scalini, Perla; Lapi, Elisabetta; Losi, Stefania; Bencini, Erica; Masoni, Fabrizio; Dosa, Laura; Becciani, Sabrina; de Martino, Maurizio

    2016-06-01

    To evaluate the hypothalamus-hypophysis-gonad axis in a cohort of children and adolescents with nonmosaic triple X syndrome. Cross-sectional study with retrospective analysis. University pediatric hospital. Fifteen prepubertal subjects (median age 9.0 years, range 6.9-11.9 years) with nonmosaic triple X syndrome and age- and pubertal-matched control group (30 girls, median age 9.1 y, range 6.9-11.6 years). None. We evaluated FSH, LH, and E2 levels and performed an autoimmunity screening as well as a pelvic ultrasonography and an LH-releasing hormone stimulation test. All triple X patients (with and without pubertal signs) showed a pubertal LH peak level that was significantly different from controls. Triple X patients showed increased basal and peak FSH and LH values compared with control subjects. However, the mean E2 level was significantly lower than control subjects. However, triple X patients showed reduced DHEAS levels and reduced inhibin levels compared with control subjects. Finally, triple X patients had a significantly reduced ovarian volume compared with control subjects, in both prepubertal and pubertal patients. Triple X patients showed premature activation of the GnRH pulse generator, even without puberty signs. Both basal and peak LH and FSH levels were higher than in control subjects, and E2 and inhibin levels and ovarian volume were reduced, which led to a reduced gonadal function. Other studies and a longitudinal evaluation is necessary to better understand the endocrinologic features of these subjects. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  10. Developmental Programming: Impact of Prenatal Exposure to Bisphenol-A and Methoxychlor on Steroid Feedbacks in Sheep

    PubMed Central

    Salloum, Bachir Abi; Steckler, Teresa L.; Herkimer, Carol; Lee, James S.; Padmanabhan, Vasantha

    2013-01-01

    Bisphenol-A (BPA), a polymer used in plastics manufacturing, and methochychlor (MXC) a pesticide, are endocrine disrupting compounds with estrogenic and anti-androgenic properties. Prenatal BPA or MXC treatment induces reproductive defects in sheep with BPA causing prepubertal luteinizing hormone (LH) hypersecretion and dampening of periovulatory LH surges and MXC lengthening follicular phase and delaying the LH surge. In this study, we addressed the underlying neuroendocrine defects by testing the following hypotheses: 1) prenatal BPA but not MXC reduces sensitivity to estradiol and progesterone negative feedback, 2) prenatal BPA but not MXC increases pituitary responsiveness to gonadotropin releasing hormone (GnRH), and 3) prenatal BPA dampens LH surge response to estradiol positive feedback challenge while prenatal MXC delays the timing of the LH surge. Pregnant sheep were treated with either 1) 5 mg/kg/day BPA (produces approximately twice the level found in human circulation, n=8), 2) 5 mg/kg/day MXC (lowest observed effect level stated in the EPA National Toxicology Program’s Report; n=6), or 3) vehicle (cotton seed oil: C: n=6) from days 30 to 90 of gestation. Female offspring of these ewes were ovariectomized at 21 months of age and tested for progesterone negative, estradiol negative, estradiol positive feedback sensitivities and pituitary responsiveness to GnRH. Results revealed that sensitivity to all 3 feedbacks as well as pituitary responsiveness to GnRH were not altered by either of the prenatal treatments. These findings suggest that the postpubertal reproductive defects seen in these animals may have stemmed from ovarian defects and the steroidal signals emanating from them. PMID:23454450

  11. Ovulatory Induction of SCG2 in Human, Nonhuman Primate, and Rodent Granulosa Cells Stimulates Ovarian Angiogenesis.

    PubMed

    Hannon, Patrick R; Duffy, Diane M; Rosewell, Katherine L; Brännström, Mats; Akin, James W; Curry, Thomas E

    2018-06-01

    The luteinizing hormone (LH) surge is essential for ovulation, but the intrafollicular factors induced by LH that mediate ovulatory processes (e.g., angiogenesis) are poorly understood, especially in women. The role of secretogranin II (SCG2) and its cleaved bioactive peptide, secretoneurin (SN), were investigated as potential mediators of ovulation by testing the hypothesis that SCG2/SN is induced in granulosa cells by human chorionic gonadotropin (hCG), via a downstream LH receptor signaling mechanism, and stimulates ovarian angiogenesis. Humans, nonhuman primates, and rodents were treated with hCG in vivo resulting in a significant increase in the messenger RNA and protein levels of SCG2 in granulosa cells collected early during the periovulatory period and just prior to ovulation (humans: 12 to 34 hours; monkeys: 12 to 36 hours; rodents: 4 to 12 hours post-hCG). This induction by hCG was recapitulated in an in vitro culture system utilizing granulosa-lutein cells from in vitro fertilization patients. Using this system, inhibition of downstream LH receptor signaling pathways revealed that the initial induction of SCG2 is regulated, in part, by epidermal growth factor receptor signaling. Further, human ovarian microvascular endothelial cells were treated with SN (1 to 100 ng/mL) and subjected to angiogenesis assays. SN significantly increased endothelial cell migration and new sprout formation, suggesting induction of ovarian angiogenesis. These results establish that SCG2 is increased in granulosa cells across species during the periovulatory period and that SN may mediate ovulatory angiogenesis in the human ovary. These findings provide insight into the regulation of human ovulation and fertility.

  12. Resumption of menstruation and pituitary response to gonadotropin-releasing hormone in functional hypothalamic amenorrhea subjects undertaking estrogen replacement therapy.

    PubMed

    Shen, Z Q; Xu, J J; Lin, J F

    2013-11-01

    Functional hypothalamic amenorrhea (FHA) refers to a functional menstrual disorder with various causes and presentations. Recovery of menstrual cyclicity is common in long-term follow-up but the affecting factors remain unknown. To explore factors affecting the menstrual resumption and to evaluate the pituitary response to gonadotropin-releasing hormone (GnRH) in FHA. Thirty cases with FHA were recruited. All subjects were put on continuous 1 mg/day estradiol valerate orally and followed up monthly. Recovery was defined as the occurrence of at least three consecutive regular cycles. Responder referred to those who recovered within two years of therapy. Gonadotropin response to the 50 μg GnRH challenge was tested every three months. Nineteen (63.3%) subjects recovered with a mean time to recovery of 26.8 months. Time to recovery was negatively correlated with body mass index (BMI) before and by amenorrhea. Twentyone cases had undertaken therapy for more than two years and 10 of them recovered. BMI before and by amenorrhea were negatively correlated with the recovery. Significant increase of serum luteinizing hormone (LH) and LH response to GnRH were noted after recovery. Menstrual resumption was common in FHA undertaking estrogen replacement therapy (ERT). The likelihood of recovery was affected by their BMI before and by amenorrhea but not by the weight gain during therapy. Low serum LH and attenuated LH response to GnRH were the main features of pituitary deficiency in FHA. The menstrual resumption in FHA was accompanied by the recovery of serum LH and the LH response to GnRH.

  13. LH-RH binding to purified pituitary plasma membranes: absence of adenylate cyclase activation.

    PubMed

    Clayton, R N; Shakespear, R A; Marshall, J C

    1978-06-01

    Purified bovine pituitary plasma membranes possess two specific LH-RH binding sites. The high affinity site (2.5 X 10(9) l/mol) has low capacity (9 X 10(-15) mol/mg membrane protein) while the low affinity site 6.1 X 10(5) l/mol) has a much higher capacity (1.1 X 10(-10) mol/mg). Specific LH-RH binding to plasma membranes is increased 8.5-fold during purification from homogenate whilst adenylate cyclase activity is enriched 7--8-fold. Distribution of specific LH-RH binding to sucrose density gradient interface fractions parallels that of adenylate cyclase activity. Mg2+ and Ca2+ inhibit specific [125I]LH-RH binding at micromolar concentrations. Synthetic LH-RH, up to 250 microgram/ml, failed to stimulate adenylase cyclase activity of the purified bovine membranes. Using a crude 10,800 g rat pituitary membrane preparation, LH-RH similarly failed to activate adenylate cyclase even in the presence of guanyl nucleotides. These data confirm the presence of LH-RH receptor sites on pituitary plasma membranes and suggest that LH-RH-induced gonadotrophin release may be mediated by mechanisms other than activation of adenylate cyclase.

  14. The use of hydrogen for aircraft propulsion in view of the fuel crisis.

    NASA Technical Reports Server (NTRS)

    Weiss, S.

    1973-01-01

    In view of projected decreases in available petroleum fuels, interest has been generated in exploiting the potential of liquid hydrogen (LH2) as an aircraft fuel. Cost studies of LH2 production show it to be more expensive than presently used fuels. Regardless of cost considerations, LH2 is viewed as an attractive aircraft fuel because of the potential performance benefits it offers. Accompanying these benefits, however, are many new problems associated with aircraft design and operations; for example, problems related to fuel system design and the handling of LH2 during ground servicing. Some of the factors influencing LH2 fuel tank design, pumping, heat exchange, and flow regulation are discussed.

  15. Ground Operations Demonstration Unit for Liquid Hydrogen (GODU LH2)

    NASA Technical Reports Server (NTRS)

    Notardonato, William U.

    2015-01-01

    When the technology associated with zero loss storage and transfer is implemented, NASA can reduce the LH2 losses and procurement costs by up to 30 compared to historical Shuttle numbers. This return on investment is based on the mission manifest and commodity use. LH2 densification can provide improved launch vehicle ascent performance by minimizing the size of the LH2 tanks or storing more mass of propellant in the given tank volume.

  16. Impact of the lipid bilayer on energy transfer kinetics in the photosynthetic protein LH2.

    PubMed

    Ogren, John I; Tong, Ashley L; Gordon, Samuel C; Chenu, Aurélia; Lu, Yue; Blankenship, Robert E; Cao, Jianshu; Schlau-Cohen, Gabriela S

    2018-03-28

    Photosynthetic purple bacteria convert solar energy to chemical energy with near unity quantum efficiency. The light-harvesting process begins with absorption of solar energy by an antenna protein called Light-Harvesting Complex 2 (LH2). Energy is subsequently transferred within LH2 and then through a network of additional light-harvesting proteins to a central location, termed the reaction center, where charge separation occurs. The energy transfer dynamics of LH2 are highly sensitive to intermolecular distances and relative organizations. As a result, minor structural perturbations can cause significant changes in these dynamics. Previous experiments have primarily been performed in two ways. One uses non-native samples where LH2 is solubilized in detergent, which can alter protein structure. The other uses complex membranes that contain multiple proteins within a large lipid area, which make it difficult to identify and distinguish perturbations caused by protein-protein interactions and lipid-protein interactions. Here, we introduce the use of the biochemical platform of model membrane discs to study the energy transfer dynamics of photosynthetic light-harvesting complexes in a near-native environment. We incorporate a single LH2 from Rhodobacter sphaeroides into membrane discs that provide a spectroscopically amenable sample in an environment more physiological than detergent but less complex than traditional membranes. This provides a simplified system to understand an individual protein and how the lipid-protein interaction affects energy transfer dynamics. We compare the energy transfer rates of detergent-solubilized LH2 with those of LH2 in membrane discs using transient absorption spectroscopy and transient absorption anisotropy. For one key energy transfer step in LH2, we observe a 30% enhancement of the rate for LH2 in membrane discs compared to that in detergent. Based on experimental results and theoretical modeling, we attribute this difference to tilting of the peripheral bacteriochlorophyll in the B800 band. These results highlight the importance of well-defined systems with near-native membrane conditions for physiologically-relevant measurements.

  17. Characterization of volatile compounds produced by Lactobacillus helveticus strains in a hard cheese model.

    PubMed

    Cuffia, Facundo; Bergamini, Carina V; Wolf, Irma V; Hynes, Erica R; Perotti, María C

    2018-01-01

    Starter cultures of Lactobacillus helveticus used in hard cooked cheeses play an important role in flavor development. In this work, we studied the capacity of three strains of L. helveticus, two autochthonous (Lh138 and Lh209) and one commercial (LhB02), to grow and to produce volatile compounds in a hard cheese extract. Bacterial counts, pH, profiles of organic acids, carbohydrates, and volatile compounds were analyzed during incubation of extracts for 14 days at 37 ℃. Lactobacilli populations were maintained at 10 6 CFU ml -1 for Lh138, while decreases of approx. 2 log orders were found for LhB02 and Lh209. Both Lh209 and LhB02 slightly increased the acetic acid content whereas mild increase in lactic acid was produced by Lh138. The patterns of volatiles were dependent on the strain which reflect their distinct enzymatic machineries: LhB02 and Lh209 produced a greater diversity of compounds, while Lh138 was the least producer strain. Extracts inoculated with LhB02 and Lh 209 were characterized by ketones, esters, alcohols, aldehydes, and acids, whereas in the extracts with Lh138 the main compounds belonged to aromatic, aldehydes, and ketones groups. Therefore, Lh209 and LhB02 could represent the best cheese starters to improve and intensify the flavor, and even a starter composed by combinations of LhB02 or Lh209 with Lh138 could also be a strategy to diversify cheese flavor.

  18. [Does a short-term hemodialysis treatment influence function of the pituitary-testicular axis in patients with chronic renal failure?].

    PubMed

    Starzyk, J; Grzeszczak, W

    1993-01-01

    Abnormal function of the pituitary-gonadal axis is a well documented endocrine abnormality in chronic renal failure (CRF). The purpose of the work was to assess the influence of the short-term haemodialysis treatment on LH, FSH and testosterone secretion. In 17 men dialyzed up to 50 months and 10 non-dialyzed male patients with advanced CRF the test of stimulation with LHRH was done. Results obtained in patients were compared with those assessed in healthy subjects. Significantly higher concentration of LH and FSH and lower concentration of testosterone in serum under basal conditions were found in patients as compared to controls. Basal concentrations of LH, FSH and testosterone in dialyzed patients and in non dialyzed men were similar. The area under the curve of LH, FSH and testosterone in both groups of patients was similar. These results suggest that in men dialyzed shorter than 50 months haemodialysis treatment does not change significantly the function of the pituitary-testicular axis as compared to men with advanced CRF.

  19. Single-molecule spectroscopy reveals that individual low-light LH2 complexes from Rhodopseudomonas palustris 2.1.6. have a heterogeneous polypeptide composition.

    PubMed

    Brotosudarmo, Tatas H P; Kunz, Ralf; Böhm, Paul; Gardiner, Alastair T; Moulisová, Vladimíra; Cogdell, Richard J; Köhler, Jürgen

    2009-09-02

    Rhodopseudomonas palustris belongs to the group of purple bacteria that have the ability to produce LH2 complexes with unusual absorption spectra when they are grown at low-light intensity. This ability is often related to the presence of multiple genes encoding the antenna apoproteins. Here we report, for the first time to our knowledge, direct evidence that individual low-light LH2 complexes have a heterogeneous alphabeta-apoprotein composition that modulates the site energies of Bchl a molecules, producing absorption bands at 800, 820, and 850 nm. The arrangement of the Bchl a molecules in the "tightly coupled ring" can be modeled by nine alphabeta-Bchls dimers, such that the Bchls bound to six alphabeta-pairs have B820-like site energies and the remaining Bchl a molecules have B850-like site energies. Furthermore, the experimental data can only be satisfactorily modeled when these six alphabeta-pairs with B820 Bchl a molecules are distributed such that the symmetry of the assembly is reduced to C(3). It is also clear from the measured single-molecule spectra that the energies of the electronically excited states in the mixed B820/850 ring are mainly influenced by diagonal disorder.

  20. Evaluating the Nature of So-Called S*-State Feature in Transient Absorption of Carotenoids in Light-Harvesting Complex 2 (LH2) from Purple Photosynthetic Bacteria.

    PubMed

    Niedzwiedzki, Dariusz M; Hunter, C Neil; Blankenship, Robert E

    2016-11-03

    Carotenoids are a class of natural pigments present in all phototrophic organisms, mainly in their light-harvesting proteins in which they play roles of accessory light absorbers and photoprotectors. Extensive time-resolved spectroscopic studies of these pigments have revealed unexpectedly complex photophysical properties, particularly for carotenoids in light-harvesting LH2 complexes from purple bacteria. An ambiguous, optically forbidden electronic excited state designated as S* has been postulated to be involved in carotenoid excitation relaxation and in an alternative carotenoid-to-bacteriochlorophyll energy transfer pathway, as well as being a precursor of the carotenoid triplet state. However, no definitive and satisfactory origin of the carotenoid S* state in these complexes has been established, despite a wide-ranging series of studies. Here, we resolve the ambiguous origin of the carotenoid S* state in LH2 complex from Rba. sphaeroides by showing that the S* feature can be seen as a combination of ground state absorption bleaching of the carotenoid pool converted to cations and the Stark spectrum of neighbor neutral carotenoids, induced by temporal electric field brought by the carotenoid cation-bacteriochlorophyll anion pair. These findings remove the need to assign an S* state, and thereby significantly simplify the photochemistry of carotenoids in these photosynthetic antenna complexes.

  1. A novel monoclonal antibody-based enzyme-linked immunosorbent assay to determine luteinizing hormone in bovine plasma.

    PubMed

    Borromeo, V; Berrini, A; De Grandi, F; Cremonesi, F; Fiandanese, N; Pocar, P; Secchi, C

    2014-07-01

    The development of a novel enzyme-linked immunosorbent assay (ELISA) for determining luteinizing hormone (LH) in bovine plasma is described. Anti-bovine LH (bLH) monoclonal antibodies (mAbs) were produced and characterized. One mAb recognizing the bLH β subunit was used for immunoaffinity purification of substantial amounts of biologically active bLH from pituitary glands. The purified bLH in combination with 2 anti-bLH β subunit mAbs was used to develop a sandwich ELISA, which satisfied all the criteria required to investigate LH secretory patterns in the bovine species. The ELISA standard curve was linear over the range 0.05 to 2.5 ng/mL, and the assay proved suitable for measuring bLH in plasma without any prior treatment of samples. Cross-reactivity and recovery tests confirmed the specificity of the method. The intra- and inter-assay coefficients of variation ranged between 3.41% and 9.40%, and 9.29% and 15.84%, respectively. The analytical specificity of the method was validated in vivo by provocative tests for LH in heifers, using the LH releasing peptide gonadotropin-releasing hormone. In conclusion, the adoption of mAbs for this ELISA for coating the wells and labeling, combined with the easy one-step production of reference bLH, ensures long-term continuity in large-scale measurements of LH in the bovine species. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. The effect of cognitive load on hemispheric asymmetries in true and false memory.

    PubMed

    Tat, Michael J; Azuma, Tamiko

    2016-01-01

    Studies examining hemispheric asymmetries in false memory have shown that the right hemisphere (RH) is more susceptible to false memories compared to the left hemisphere (LH). Theories suggest that hemispheric asymmetries in true and false memory may be due to differences in representational coding and the use of top-down mechanisms in each hemisphere. In the current study, the Deese-Roediger-McDermott false memory paradigm was used in conjunction with divided visual field presentation to examine the role of top-down mechanisms in hemispheric asymmetries of true and false memory. In Experiment 1, participants studied lists of related words while completing secondary cognitive load tasks. In Experiment 2, the secondary tasks were administered during memory retrieval instead of memory encoding. Results revealed that cognitive loads imposed during the study phase influenced veridical memory in the LH more than the RH, but cognitive loads imposed during retrieval did not influence veridical memory in either hemisphere. Surprisingly, false memory rates were not influenced by cognitive loads and were higher in the LH. These data provide evidence that, at least for veridical memory, top-down control mechanisms are used more readily for the encoding of information into memory in the LH compared to the RH.

  3. Dual nozzle design update. [on liquid rocket engines for advanced earth-to-orbit transportation systems

    NASA Technical Reports Server (NTRS)

    Obrien, C. J.

    1982-01-01

    Dual-nozzle engines, such as the dual-throat and dual-expander engines, are being evaluated for advanced earth-to-orbit transportation systems. Potential derivatives of the Space Shuttle and completely new vehicles might benefit from these advanced engines. In this paper, progress in the design of single-fuel and dual-fuel dual-nozzle engines is summarized. Dual-nozzle engines include those burning propellants such as LOX/RP-1/LH2, LOX/LC3H8/LH2, LOX/LCH4/LH2, LOX/LH2/LH2, LOX/LCH4/LCH4, LOX/LC3H8/C3H8 and N2O4/MMH/LH2. Engine data are applicable for thrust levels from 200,000 through 670,000 lbF. The results indicate that several versions of these engines utilize state-of-the-art technology and that even advanced versions of these engines do not require a major breakthrough in technology.

  4. Polarized-cathodoluminescence study of uniaxial and biaxial stress in GaAs/Si

    NASA Technical Reports Server (NTRS)

    Rich, D. H.; Ksendzov, A.; Terhune, R. W.; Grunthaner, F. J.; Wilson, B. A.; Shen, H.; Dutta, M.; Vernon, S. M.; Dixon, T. M.

    1991-01-01

    The strain-induced splitting of the heavy-hole (hh) and light-hole (lh) valence bands for 4-microns thick GaAs/Si is examined on a microscopic scale using linear polarized-cathodoluminescence imaging and spectroscopy. The energies and intensities of the hh- and lh-exciton luminescence are quantitatively analyzed to determine spatial variations in the stress tensor. The results indicate that regions near and far from the microcracks are primarily subject to uniaxial and biaxial tensile stresses, respectively. The transition region where biaxial stress gradually converts to uniaxial stress is analyzed, and reveals a mixing of lh and hh characters in the strain-split bands.

  5. Lateral Hypothalamus Contains Two Types of Palatability-Related Taste Responses with Distinct Dynamics

    PubMed Central

    Yoshida, Takashi; Monk, Kevin J.; Katz, Donald B.

    2013-01-01

    The taste of foods, in particular the palatability of these tastes, exerts a powerful influence on our feeding choices. Although the lateral hypothalamus (LH) has long been known to regulate feeding behavior, taste processing in LH remains relatively understudied. Here, we examined single-unit LH responses in rats subjected to a battery of taste stimuli that differed in both chemical composition and palatability. Like neurons in cortex and amygdala, LH neurons produced a brief epoch of nonspecific responses followed by a protracted period of taste-specific firing. Unlike in cortex, however, where palatability-related information only appears 500 ms after the onset of taste-specific firing, taste specificity in LH was dominated by palatability-related firing, consistent with LH's role as a feeding center. Upon closer inspection, taste-specific LH neurons fell reliably into one of two subtypes: the first type showed a reliable affinity for palatable tastes, low spontaneous firing rates, phasic responses, and relatively narrow tuning; the second type showed strongest modulation to aversive tastes, high spontaneous firing rates, protracted responses, and broader tuning. Although neurons producing both types of responses were found within the same regions of LH, cross-correlation analyses suggest that they may participate in distinct functional networks. Our data shed light on the implementation of palatability processing both within LH and throughout the taste circuit, and may ultimately have implications for LH's role in the formation and maintenance of taste preferences and aversions. PMID:23719813

  6. Lateral hypothalamus contains two types of palatability-related taste responses with distinct dynamics.

    PubMed

    Li, Jennifer X; Yoshida, Takashi; Monk, Kevin J; Katz, Donald B

    2013-05-29

    The taste of foods, in particular the palatability of these tastes, exerts a powerful influence on our feeding choices. Although the lateral hypothalamus (LH) has long been known to regulate feeding behavior, taste processing in LH remains relatively understudied. Here, we examined single-unit LH responses in rats subjected to a battery of taste stimuli that differed in both chemical composition and palatability. Like neurons in cortex and amygdala, LH neurons produced a brief epoch of nonspecific responses followed by a protracted period of taste-specific firing. Unlike in cortex, however, where palatability-related information only appears 500 ms after the onset of taste-specific firing, taste specificity in LH was dominated by palatability-related firing, consistent with LH's role as a feeding center. Upon closer inspection, taste-specific LH neurons fell reliably into one of two subtypes: the first type showed a reliable affinity for palatable tastes, low spontaneous firing rates, phasic responses, and relatively narrow tuning; the second type showed strongest modulation to aversive tastes, high spontaneous firing rates, protracted responses, and broader tuning. Although neurons producing both types of responses were found within the same regions of LH, cross-correlation analyses suggest that they may participate in distinct functional networks. Our data shed light on the implementation of palatability processing both within LH and throughout the taste circuit, and may ultimately have implications for LH's role in the formation and maintenance of taste preferences and aversions.

  7. Pituitary content of luteinizing hormone reveals species differences in the reproductive synchrony between males and females in Australian flying-foxes (genus Pteropus).

    PubMed

    O'Brien, G M; McFarlane, J R; Kearney, P J

    2003-01-01

    Flying-foxes (genus suborder, Pteropus Megachiroptera) are long-lived tropical mammals. Their seasonal reproduction appears to be regulated by an endogenous, circannual rhythm modified by multiple environmental cues. Luteinizing hormone (LH) content in pituitary extracts was examined to establish the broad time-frame of pituitary stages in the reproductive seasonality of the flying-foxes. A comparison was made between the grey-headed flying-fox P. poliocephalus, which mates and conceives in autumn, and the little red flying-fox P. scapulatus, which mates and conceives in spring. In P. scapulatus, LH was maximum during the spring mating season at 1494 ng mg(-1) in males and 896 ng mg(-1) in females. In P. poliocephalus males, LH increased to 1082 ng mg(-1) in early summer, 4 months before the mating season; LH concentrations in male P. poliocephalus returned to a low of 222 ng mg(-1) by the time of the autumn mating, by which time the female P. poliocephalus expressed elevated LH concentrations (624 ng mg(-1)). Apparently in P. poliocephalus, the peak LH concentrations in females are delayed by 4 months relative to LH concentrations in males. This is associated with 4 months of energetic courtship on the part of male P. poliocephalus, which is not observed in P. scapulatus, the fertility of which is synchronized between the sexes. The heterologous radioimmunoassay developed using monoclonal antibody 518B7 confirmed classic suppression of LH during pregnancy and lactation in flying-foxes and LH elevation in response to gonadectomy. Juveniles generally had pituitary levels similar to non-breeding levels in adults.

  8. LH2 airport requirements study

    NASA Technical Reports Server (NTRS)

    Brewer, G. D. (Editor)

    1976-01-01

    A preliminary assessment of the facilities and equipment which will be required at a representative airport is provided so liquid hydrogen LH2 can be used as fuel in long range transport aircraft in 1995-2000. A complete facility was conceptually designed, sized to meet the projected air traffic requirement. The facility includes the liquefaction plant, LH2, storage capability, and LH2 fuel handling system. The requirements for ground support and maintenance for the LH2 fueled aircraft were analyzed. An estimate was made of capital and operating costs which might be expected for the facility. Recommendations were made for design modifications to the reference aircraft, reflecting results of the analysis of airport fuel handling requirements, and for a program of additional technology development for air terminal related items.

  9. Effects of Calcium Ions on the Thermostability and Spectroscopic Properties of the LH1-RC Complex from a New Thermophilic Purple Bacterium Allochromatium tepidum.

    PubMed

    Kimura, Yukihiro; Lyu, Shuwen; Okoshi, Akira; Okazaki, Koudai; Nakamura, Natsuki; Ohashi, Akira; Ohno, Takashi; Kobayashi, Manami; Imanishi, Michie; Takaichi, Shinichi; Madigan, Michael T; Wang-Otomo, Zheng-Yu

    2017-05-18

    The light harvesting-reaction center (LH1-RC) complex from a new thermophilic purple sulfur bacterium Allochromatium (Alc.) tepidum was isolated and characterized by spectroscopic and thermodynamic analyses. The purified Alc. tepidum LH1-RC complex showed a high thermostability comparable to that of another thermophilic purple sulfur bacterium Thermochromatium tepidum, and spectroscopic characteristics similar to those of a mesophilic bacterium Alc. vinosum. Approximately 4-5 Ca 2+ per LH1-RC were detected by inductively coupled plasma atomic emission spectroscopy and isothermal titration calorimetry. Upon removal of Ca 2+ , the denaturing temperature of the Alc. tepidum LH1-RC complex dropped accompanied by a blue-shift of the LH1 Q y absorption band. The effect of Ca 2+ was also observed in the resonance Raman shift of the C3-acetyl νC═O band of bacteriochlorophyll-a, indicating changes in the hydrogen-bonding interactions between the pigment and LH1 polypeptides. Thermodynamic parameters for the Ca 2+ -binding to the Alc. tepidum LH1-RC complex indicated that this reaction is predominantly driven by the largely favorable electrostatic interactions that counteract the unfavorable negative entropy change. Our data support a hypothesis that Alc. tepidum may be a transitional organism between mesophilic and thermophilic purple bacteria and that Ca 2+ is one of the major keys to the thermostability of LH1-RC complexes in purple bacteria.

  10. Serum levels of inhibin A and inhibin B in women with normal and abnormal luteal function.

    PubMed

    Yamoto, M; Imai, M; Otani, H; Nakano, R

    1997-05-01

    To determine whether serum inhibin A and inhibin B concentrations are lower in patients with luteal dysfunction than in women with normal luteal function. Serum samples were collected from seven healthy women with regular menstrual cycles. Serum samples on days +5 to +9 after the LH surge were collected from patients with luteal dysfunction. The diagnosis of luteal dysfunction was based on a luteal phase duration less than 11 days and a single midluteal progesterone level below 10 ng/mL. Serum levels of inhibin A, inhibin B, progesterone, estradiol (E2), FSH, and LH were measured. The serum inhibin A levels were increased toward the late follicular phase. The levels reached a maximum during the midluteal phase, followed by a fall during the late luteal phase. The serum inhibin B levels were high during the follicular phases and the early luteal phase. The levels decreased during the midluteal and late luteal phases. Serum levels (mean +/- standard error of the mean) of inhibin A in patients with luteal dysfunction were significantly lower than those in women during the midluteal phase (26.2 +/- 2.9 compared to 41.9 +/- 2.8 pg/mL; P < .01) in addition to the expected decrease in serum progesterone levels (6.3 +/- 0.7 compared to 14.7 +/- 1.2 ng/mL; P < .01). Serum inhibin B levels did not differ significantly between normal women and those with luteal dysfunction. There also were no significant differences in the E2, FSH, and LH levels. Levels of inhibin A, but not of inhibin B, may reflect the human luteal function.

  11. Conceptual Design, Feasibility and Payoff Analysis of a Third Stage for EELV (Briefing Charts)

    DTIC Science & Technology

    2014-07-30

    performance capability – Hydrazine, N2O4/MMH, LOX/RP, H2O2/RP, LOX/CH4, LOX/ LH2 (MR of 6), and LOX/ LH2 (MR of 10) • Propulsion system split into multiple...area ratio attainable within length envelope – Use of four chambers allows area ratios >150 – LOX/ LH2 (MR=6) is highest performing propellant...combination •Due to LOX/ LH2 (MR=6) low bulk density it is not possible to store as much propellant within stage – Resulting in the lowest total

  12. Empirical Profiling of Cold Hydrogen Plumes Formed from Venting Of LH2 Storage Vessels: Preprint

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Buttner, William J; Rivkin, Carl H; Schmidt, Kara

    Liquid hydrogen (LH2) storage is a viable approach to assuring sufficient hydrogen capacity at commercial fuelling stations. Presently, LH2 is produced at remote facilities and then transported to the end-use site by road vehicles (i.e., LH2 tanker trucks). Venting of hydrogen to depressurize the transport storage tank is a routine part of the LH2 delivery process. The behaviour of cold hydrogen plumes has not been well-characterized because empirical field data is essentially non-existent. The NFPA 2 Hydrogen Storage Safety Task Group, which consists of hydrogen producers, safety experts, and CFD modellers, has identified the lack of understanding of hydrogen dispersionmore » during LH2 venting of storage vessel as a critical gap for establishing safety distances at LH2 facilities, especially commercial hydrogen fuelling stations. To address this need, the NREL sensor laboratory, in collaboration with the NFPA 2 Safety Task Group developed the Cold Hydrogen Plume Analyzer to empirically characterize the hydrogen plume formed during LH2 storage tank venting. A prototype Analyzer was developed and field-deployed at an actual LH2 venting operation with critical findings that included: - H2 being detected as much as 2 m lower than the release point, which is not predicted by existing models - A small and inconsistent correlation between oxygen depletion and the hydrogen concentration - A negligible to non-existent correlation between in-situ temperature and the hydrogen concentration The Analyzer is currently being upgraded for enhanced metrological capabilities including improved real-time spatial and temporal profiling of the plume and tracking of prevailing weather conditions. Additional deployments are planned to monitor plume behaviour under different wind, humidity, and temperatures. This data will be shared with the NFPA 2 Safety Task Group and ultimately will be used support theoretical models and code requirements prescribed in NFPA 2.« less

  13. Survey on the phage resistance mechanisms displayed by a dairy Lactobacillus helveticus strain.

    PubMed

    Zago, Miriam; Orrù, Luigi; Rossetti, Lia; Lamontanara, Antonella; Fornasari, Maria Emanuela; Bonvini, Barbara; Meucci, Aurora; Carminati, Domenico; Cattivelli, Luigi; Giraffa, Giorgio

    2017-09-01

    In this study the presence and functionality of phage defence mechanisms in Lactobacillus helveticus ATCC 10386, a strain of dairy origin which is sensitive to ΦLh56, were investigated. After exposure of ATCC 10386 to ΦLh56, the whole-genome sequences of ATCC 10386 and of a phage-resistant derivative (LhM3) were compared. LhM3 showed deletions in the S-layer protein and a higher expression of the genes involved in the restriction/modification (R/M) system. Genetic data were substantiated by measurements of bacteriophage adsorption rates, efficiency of plaquing, cell wall protein size and by gene expression analysis. In LhM3 two phage resistance mechanisms, the inhibition of phage adsorption and the upregulation of Type I R/M genes, take place and explain its resistance to ΦLh56. Although present in both ATCC 10386 and LhM3 genomes, the CRISPR machinery did not seem to play a role in the phage resistance of LhM3. Overall, the natural selection of phage resistant strains resulted successful in detecting variants carrying multiple phage defence mechanisms in L. helveticus. The concurrent presence of multiple phage-resistance systems should provide starter strains with increased fitness and robustness in dairy ecosystems. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Influence of ethynylestradiol and methyltestosterone on the hypothalamo-hypophyseal-gonadal axis of adult air-breathing catfish, Clarias gariepinus.

    PubMed

    Swapna, I; Senthilkumaran, B

    2009-11-27

    Adult male and female air-breathing catfish Clarias gariepinus were treated with ethynylestradiol (EE(2)) and methyltestosterone (MT) at concentrations of 1microg/L, respectively for 21 days. EE(2) treatment caused disappearance of spermatids/sperm from several testicular lumen/lobules in males while MT treatment to females led to precocious ovarian development. EE(2) caused significant fluid retention in all tissues including peritoneal cavity and seminal vesicles. Immunocytochemical localization of catfish GnRH (cfGnRH) and luteinizing hormone (LH) in preoptic area-hypothalamus (POA-H) and pituitary, respectively, revealed decreased immunoreactivity (ir-) following EE(2) treatment in males. MT treatment however caused no observable change in cfGnRH ir- and a significant increase in LH ir- in females. Semi-quantitative RT-PCR analysis indicated that cfGnRH transcripts in POA-H decreased significantly following EE(2) and MT treatment in males and females, respectively. Levels of POA-H dopamine (inhibitory monoamine for gonadotropin [GTH] synthesis and release) increased following EE(2) and MT treatment in males and females while levels of serotonin and norepinephrine (GTH-stimulatory monoamines) decreased significantly. The results demonstrate a direct in vivo effect of sex steroid analogs on cfGnRH-LH axis and monoaminergic system vis-à-vis on gonads in addition to probable direct action on gonads.

  15. [Effects of autologous blood injection at Zusanli (ST 36) on ovarian function in patients with primary ovarian insufficiency].

    PubMed

    Jiang, Renjian; Zou, Yu

    2017-11-12

    To observe the effects of autologous blood injection and 0.9% NaCl at Zusanli (ST 36) on ovarian function in patients with primary ovarian insufficiency. Sixty patients with primary ovarian insufficiency were randomly divided into an observation group and a control group, 30 cases in each one. The patients in the observation group were treated with injection of autologous blood at Zusanli (ST 36); the patients in the control group were treated with 0.9% NaCl with identical volume at Zusanli (ST 36). Both the treatments were given once a week for 3 months. The ovarian function, including follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E 2 ) were tested before treatment, 1 month, 2 months and 3 months after first acupoint injection; the endometrial thickness before and after treatment and clinical efficacy were compared in the two groups. Compared before treatment, FSH was lowered in the observation group after 1-month treatment ( P <0.05), while FSH and LH were lowered and E 2 was increased after 2-month treatment and 3-month treatment (all P <0.05). Compared with 1-month treatment, FSH and LH were lowered and E 2 was increased in the observation group after 2-month treatment and 3-month treatment (all P <0.05). Compared with 2-month treatment, FSH was lowered and E 2 was increased in the observation group after 3-month treatment (both P <0.05). The differences of all serum tests before and after treatment were insignificant in the control group (all P >0.05). The FSH after 1-month treatment, and FSH, LH and E 2 after 2-month treatment and 3-month treatment in the observation group were significantly different from those in the control group (all P <0.05). The endometrial thickness after treatment in the observation group was higher than that before treatment ( P <0.05), while the endometrial thickness after treatment in the control group was similar to that before treatment ( P >0.05); the difference of endometrial thickness before and after treatment in the observation group was higher than that in the control group ( P <0.05). The clinical effective rate was 83.3% (25/30) in the observation group, which was superior to 46.7% (14/30) in the control group ( P <0.05). The autologous blood injection at Zusanli (ST 36) can significantly improve ovarian function, promote endometrial growth in patients with primary ovarian insufficiency.

  16. Future orbital transfer vehicle technology study. Volume 1: Executive summary

    NASA Technical Reports Server (NTRS)

    Davis, E. E.

    1982-01-01

    Reusable space and ground based LO2/LH2 OTV's, both advanced space engines and aero assist capability were compared. The SB OTV provided advantages in life cycle cost, performance and potential for improvement. An all LO2/LH2 OTV fleet was also compared with a fleet of LO2/.H2 OTV's and electric OTV's. The normal growth technology electric OTV used silicon cells with heavy shielding and argon ion thrusters. In this case, the LO2/LH2 OTV fleet provided a 23% advantage in total transportation cost. An accelerated technology LF2/LH2 OTV provided improvements in performance relative to LO2/.H2 OTV but has higher DDT&E cost which negated its cost effectiveness. The accelerated technology electric vehicle used GaAs cells and annealing but still did not result in the mixed fleet being any cheaper than an all LO2/LH2 OTV fleet. It is concluded that reusable LO2/LH2 OTV's can serve all general purpose cargo roles between LEO and GEO for the forseeable future. The most significant technology for the second generation vehicle would be space debris protection, on orbit propellant storage and transfer and on orbit maintenance capability.

  17. [Hemispheric asymmetry modulation for language processing in aging: meta-analysis of studies using the dichotic listening test].

    PubMed

    Vanhoucke, Elodie; Cousin, Emilie; Baciu, Monica

    2013-03-01

    Growing evidence suggests that age impacts on interhemispheric representation of language. Dichotic listening test allows assessing language lateralization for spoken language and it generally reveals right-ear/left-hemisphere (LH) predominance for language in young adult subjects. According to reported results, elderly would display increasing LH predominance in some studies or stable LH language lateralization for language in others ones. The aim of this study was to depict the main pattern of results in respect with the effect of normal aging on the hemisphere specialization for language by using dichotic listening test. A meta-analysis based on 11 studies has been performed. The inter-hemisphere asymmetry does not seem to increase according to age. A supplementary qualitative analysis suggests that right-ear advantage seems to increase between 40 and 49 y old and becomes stable or decreases after 55 y old, suggesting right-ear/LH decline.

  18. Effect of monosaccharide sugars on LH-induced differentiation and sugar transport facilitator (SLC2A) expression in sheep theca cells in vitro.

    PubMed

    Campbell, B K; Kendall, N R; Onions, V; Guo, L; Scaramuzzi, R J

    2014-03-01

    The aim of the present study was to investigate the effects of glucose, galactose and fructose on the LH-induced differentiation and mRNA expression of sugar transport facilitators (SLC2A) by sheep thecal cells derived from small antral follicles cultured under serum-free conditions for 6 days. The dose and type of monosaccharide had a significant effect on LH-induced androstenedione production by theca cells and there was a significant interaction (P<0.001). Glucose and galactose were used with equal efficiency so that cell numbers and androstenedione production at the end of the culture were comparable. Pharmacological doses of glucose (16.7 mM) inhibited steroidogenesis (P<0.05). Cell numbers and androstenedione production by cells cultured with fructose were lower than for cells cultured with either glucose or galactose (P<0.001). None of the monosaccharides resulted in the production of lactate. Expression of SLC2A1, SLC2A4 and SLC2A8, but not SLC2A5, mRNA was detected in fresh and cultured theca cells. Large doses (16.7 mM) of glucose and fructose, but not galactose, suppressed (P<0.05) SLC2A expression. The results show that glucose and galactose, but not fructose, are readily metabolised via oxidative pathways to support LH-induced differentiation of sheep theca cells. Further work is required to determine the mechanisms resulting in these differences in relation to the established effects of nutrition on reproductive function.

  19. Alterations in Hormone Levels After Adjuvant Chemoradiation in Male Rectal Cancer Patients

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yoon, Frederick H.; Perera, Francisco; Fisher, Barbara

    Purpose: To evaluate follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels after postoperative chemoradiation in men with rectal cancer. Methods and Materials: Forty-three men with rectal cancer had baseline and postchemoradiation FSH, LH, and testosterone measured. Adjuvant chemoradiation consisted of two 5-day cycles of bolus 5-fluorouracil (5-FU) every 4 weeks at a dose of 500 mg/m{sup 2}/d followed by concurrent chemoradiation followed by two additional 5-day cycles of 5-FU at a dose of 450 mg/m{sup 2}/d. Continuous-infusion 5-FU at 225 mg/m{sup 2}/d was given during radiation. Pelvic radiation consisted of a three- or four-field technique with a median dosemore » of 54.0 Gy in 30 fractions. Results: Median follow-up was 6.1 years. Mean baseline FSH levels increased from 5.3 to a peak of 23.9 IU/L (p < 0.001) 13-24 months after chemoradiation. Mean baseline LH levels increased from 4.3 to a peak of 8.5 IU/L (p < 0.001) within 6 months after chemoradiation. Mean testosterone levels decreased from 15.4 nmol/L at baseline to 8.0 nmol/L more than 4 years after chemoradiation. Mean testosterone to mean LH ratio decreased from 4.4 at baseline to 1.1 after 48 months posttreatment, suggesting a continued decrease in Leydig cell function with time. Testicular dose was measured in 5 patients. Median dose was 4 Gy (range, 1.5-8.9 Gy). Conclusions: Chemoradiation in men with rectal cancer causes persistent increases in FSH and LH levels and decreases in testosterone levels.« less

  20. Groundwater shapes sediment biogeochemistry and microbial diversity in a submerged Great Lake sinkhole.

    PubMed

    Kinsman-Costello, L E; Sheik, C S; Sheldon, N D; Allen Burton, G; Costello, D M; Marcus, D; Uyl, P A Den; Dick, G J

    2017-03-01

    For a large part of earth's history, cyanobacterial mats thrived in low-oxygen conditions, yet our understanding of their ecological functioning is limited. Extant cyanobacterial mats provide windows into the putative functioning of ancient ecosystems, and they continue to mediate biogeochemical transformations and nutrient transport across the sediment-water interface in modern ecosystems. The structure and function of benthic mats are shaped by biogeochemical processes in underlying sediments. A modern cyanobacterial mat system in a submerged sinkhole of Lake Huron (LH) provides a unique opportunity to explore such sediment-mat interactions. In the Middle Island Sinkhole (MIS), seeping groundwater establishes a low-oxygen, sulfidic environment in which a microbial mat dominated by Phormidium and Planktothrix that is capable of both anoxygenic and oxygenic photosynthesis, as well as chemosynthesis, thrives. We explored the coupled microbial community composition and biogeochemical functioning of organic-rich, sulfidic sediments underlying the surface mat. Microbial communities were diverse and vertically stratified to 12 cm sediment depth. In contrast to previous studies, which used low-throughput or shotgun metagenomic approaches, our high-throughput 16S rRNA gene sequencing approach revealed extensive diversity. This diversity was present within microbial groups, including putative sulfate-reducing taxa of Deltaproteobacteria, some of which exhibited differential abundance patterns in the mats and with depth in the underlying sediments. The biological and geochemical conditions in the MIS were distinctly different from those in typical LH sediments of comparable depth. We found evidence for active cycling of sulfur, methane, and nutrients leading to high concentrations of sulfide, ammonium, and phosphorus in sediments underlying cyanobacterial mats. Indicators of nutrient availability were significantly related to MIS microbial community composition, while LH communities were also shaped by indicators of subsurface groundwater influence. These results show that interactions between the mats and sediments are crucial for sustaining this hot spot of biological diversity and biogeochemical cycling. © 2016 John Wiley & Sons Ltd.

  1. Experimental investigation of density behaviors in front of the lower hybrid launcher in experimental advanced superconducting tokamak

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, L.; Ding, B. J.; Li, M. H.

    2013-06-15

    A triple Langmuir probe is mounted on the top of the Lower Hybrid (LH) antenna to measure the electron density near the LH grills in Experimental Advanced Superconducting Tokamak. In this work, the LH power density ranges from 2.3 MWm{sup −2} to 10.3 MWm{sup −2} and the rate of puffing gas varies from 1.7 × 10{sup 20} el/s to 14 × 10{sup 20} el/s. The relation between the edge density (from 0.3 × n{sub e-cutoff} to 20 × n{sub e-cutoff}, where n{sub e-cutoff} is the cutoff density, n{sub e-cutoff} = 0.74 × 10{sup 17} m{sup −3} for 2.45 GHz lowermore » hybrid current drive) near the LH grill and the LH power reflection coefficients is investigated. The factors, including the gap between the LH grills and the last closed magnetic flux surface, line-averaged density, LH power, edge safety factor, and gas puffing, are analyzed. The experiments show that injection of LH power is beneficial for increasing edge density. Gas puffing is beneficial for increasing grill density but excess gas puffing is unfavorable for coupling and current drive.« less

  2. Association between socioeconomic status, learned helplessness, and disease outcome in patients with inflammatory polyarthritis.

    PubMed

    Camacho, E M; Verstappen, S M M; Symmons, D P M

    2012-08-01

    Independent investigations have shown that socioeconomic status (SES) and learned helplessness (LH) are associated with poor disease outcome in patients with rheumatoid arthritis (RA). Our aim was to investigate the cross-sectional relationship between SES, LH, and disease outcome in patients with recent-onset inflammatory polyarthritis (IP), the broader group of conditions of which RA is the major constituent. SES was measured using the Index of Multiple Deprivation 2007 for 553 patients consecutively recruited to the Norfolk Arthritis Register. Patients also completed the Rheumatology Attitudes Index, a measure of LH. SES and LH were investigated as predictors of disease outcome (functional disability [Health Assessment Questionnaire (HAQ)] and disease activity [Disease Activity Score in 28 joints]) in a regression analysis, adjusted for age, sex, and symptom duration. The role of LH in the relationship between SES and disease outcome was then investigated. Compared to patients of the highest SES, those of the lowest SES had a significantly worse outcome (median difference in HAQ score 0.42; 95% confidence interval [95% CI] 0.08, 0.75). Compared to patients with normal LH, patients with low LH had a significantly better outcome and patients with high LH had a significantly worse outcome (median difference in HAQ score 1.12; 95% CI 0.82, 1.41). There was a significant likelihood that LH mediated the association between SES and disease outcome (P = 0.04). LH is robustly associated with cross-sectional disease outcome in patients with IP, and appears to mediate the relationship between SES and disease outcome. As LH is potentially modifiable, these findings have potential clinical implications. Copyright © 2012 by the American College of Rheumatology.

  3. Association between socioeconomic status, learned helplessness, and disease outcome in patients with inflammatory polyarthritis

    PubMed Central

    Camacho, E M; Verstappen, S M M; Symmons, D P M

    2012-01-01

    Objective Independent investigations have shown that socioeconomic status (SES) and learned helplessness (LH) are associated with poor disease outcome in patients with rheumatoid arthritis (RA). Our aim was to investigate the cross-sectional relationship between SES, LH, and disease outcome in patients with recent-onset inflammatory polyarthritis (IP), the broader group of conditions of which RA is the major constituent. Methods SES was measured using the Index of Multiple Deprivation 2007 for 553 patients consecutively recruited to the Norfolk Arthritis Register. Patients also completed the Rheumatology Attitudes Index, a measure of LH. SES and LH were investigated as predictors of disease outcome (functional disability [Health Assessment Questionnaire (HAQ)] and disease activity [Disease Activity Score in 28 joints]) in a regression analysis, adjusted for age, sex, and symptom duration. The role of LH in the relationship between SES and disease outcome was then investigated. Results Compared to patients of the highest SES, those of the lowest SES had a significantly worse outcome (median difference in HAQ score 0.42; 95% confidence interval [95% CI] 0.08, 0.75). Compared to patients with normal LH, patients with low LH had a significantly better outcome and patients with high LH had a significantly worse outcome (median difference in HAQ score 1.12; 95% CI 0.82, 1.41). There was a significant likelihood that LH mediated the association between SES and disease outcome (P = 0.04). Conclusion LH is robustly associated with cross-sectional disease outcome in patients with IP, and appears to mediate the relationship between SES and disease outcome. As LH is potentially modifiable, these findings have potential clinical implications. PMID:22438290

  4. The memory that’s right and the memory that’s left: Event-related potentials reveal hemispheric asymmetries in the encoding and retention of verbal information

    PubMed Central

    Evans, Karen M.; Federmeier, Kara D.

    2009-01-01

    We examined the nature and timecourse of hemispheric asymmetries in verbal memory by recording event-related potentials (ERPs) in a continuous recognition task. Participants made overt recognition judgments to test words presented in central vision that were either novel (new words) or had been previously presented in the left or right visual field (old words). An ERP memory effect linked to explicit retrieval revealed no asymmetries for words repeated at short and medium retention intervals, but at longer repetition lags (20–50 intervening words) this ‘old/new effect’ was more pronounced for words whose study presentation had been biased to the right hemisphere (RH). Additionally, a repetition effect linked to more implicit recognition processes (P2 amplitude changes) was observed at all lags for words preferentially encoded by the RH but was not observed for left hemisphere (LH)-encoded words. These results are consistent with theories that the RH encodes verbal stimuli more veridically whereas the LH encodes in a more abstract manner. The current findings provide a critical link between prior work on memory asymmetries, which has emphasized general LH advantages for verbal material, and on language comprehension, which has pointed to an important role for the RH in language processes that require the retention and integration of verbal information over long time spans. PMID:17291547

  5. Optimization of permeate flux produced by solar energy driven membrane distillation process using central composite design approach.

    PubMed

    Bouguecha, Salah T; Boubakri, Ali; Aly, Samir E; Al-Beirutty, Mohammad H; Hamdi, Mohamed M

    2016-01-01

    Membrane distillation (MD) is considered as a relatively high-energy requirement. To overcome this drawback, it is recommended to couple the MD process with solar energy as the renewable energy source in order to provide heat energy required to optimize its performance to produce permeate flux. In the present work, an original solar energy driven direct contact membrane distillation (DCMD) pilot plant was built and tested under actual weather conditions at Jeddah, KSA, in order to model and optimize permeate flux. The dependency of permeate flux on various operating parameters such as feed temperature (46.6-63.4°C), permeate temperature (6.6-23.4°C), feed flow rate (199-451L/h) and permeate flow rate (199-451L/h) was studied by response surface methodology based on central composite design approach. The analysis of variance (ANOVA) confirmed that all independent variables had significant influence on the model (where P-value <0.05). The high coefficient of determination (R(2) = 0.9644 and R(adj)(2) = 0.9261) obtained by ANOVA demonstrated good correlation between experimental and predicted values of the response. The optimized conditions, determined using desirability function, were T(f) = 63.4°C, Tp = 6.6°C, Q(f) = 451L/h and Q(p) = 451L/h. Under these conditions, the maximum permeate flux of 6.122 kg/m(2).h was achieved, which was close to the predicted value of 6.398 kg/m(2).h.

  6. Impact of the lipid bilayer on energy transfer kinetics in the photosynthetic protein LH2† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc04814a

    PubMed Central

    Ogren, John I.; Tong, Ashley L.; Gordon, Samuel C.; Chenu, Aurélia; Lu, Yue; Blankenship, Robert E.; Cao, Jianshu

    2018-01-01

    Photosynthetic purple bacteria convert solar energy to chemical energy with near unity quantum efficiency. The light-harvesting process begins with absorption of solar energy by an antenna protein called Light-Harvesting Complex 2 (LH2). Energy is subsequently transferred within LH2 and then through a network of additional light-harvesting proteins to a central location, termed the reaction center, where charge separation occurs. The energy transfer dynamics of LH2 are highly sensitive to intermolecular distances and relative organizations. As a result, minor structural perturbations can cause significant changes in these dynamics. Previous experiments have primarily been performed in two ways. One uses non-native samples where LH2 is solubilized in detergent, which can alter protein structure. The other uses complex membranes that contain multiple proteins within a large lipid area, which make it difficult to identify and distinguish perturbations caused by protein–protein interactions and lipid–protein interactions. Here, we introduce the use of the biochemical platform of model membrane discs to study the energy transfer dynamics of photosynthetic light-harvesting complexes in a near-native environment. We incorporate a single LH2 from Rhodobacter sphaeroides into membrane discs that provide a spectroscopically amenable sample in an environment more physiological than detergent but less complex than traditional membranes. This provides a simplified system to understand an individual protein and how the lipid–protein interaction affects energy transfer dynamics. We compare the energy transfer rates of detergent-solubilized LH2 with those of LH2 in membrane discs using transient absorption spectroscopy and transient absorption anisotropy. For one key energy transfer step in LH2, we observe a 30% enhancement of the rate for LH2 in membrane discs compared to that in detergent. Based on experimental results and theoretical modeling, we attribute this difference to tilting of the peripheral bacteriochlorophyll in the B800 band. These results highlight the importance of well-defined systems with near-native membrane conditions for physiologically-relevant measurements. PMID:29732092

  7. Radioiodination of chicken luteinizing hormone without affecting receptor binding potency

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kikuchi, M.; Ishii, S.

    1989-12-01

    By improving the currently used lactoperoxidase method, we were able to obtain radioiodinated chicken luteinizing hormone (LH) that shows high specific binding and low nonspecific binding to a crude plasma membrane fraction of testicular cells of the domestic fowl and the Japanese quail, and to the ovarian granulosa cells of the Japanese quail. The change we made from the original method consisted of (1) using chicken LH for radioiodination that was not only highly purified but also retained a high receptor binding potency; (2) controlling the level of incorporation of radioiodine into chicken LH molecules by employing a short reactionmore » time and low temperature; and (3) fractionating radioiodinated chicken LH further by gel filtration using high-performance liquid chromatography. Specific radioactivity of the final {sup 125}I-labeled chicken LH preparation was 14 microCi/micrograms. When specific binding was 12-16%, nonspecific binding was as low as 2-4% in the gonadal receptors. {sup 125}I-Labeled chicken LH was displaced by chicken LH and ovine LH but not by chicken follicle-stimulating hormone. The equilibrium association constant of quail testicular receptor was 3.6 x 10(9) M-1. We concluded that chicken LH radioiodinated by the present method is useful for studies of avian LH receptors.« less

  8. Ovarian hyperstimulation, hyperprolactinaemia and LH gonadotroph adenoma.

    PubMed

    Castelo-Branco, Camil; del Pino, Marta; Valladares, Esther

    2009-08-01

    This report considers a highly exceptional case of ovarian hyperstimulation syndrome due to a gonadotroph adenoma secreting LH in a 31-year-old patient who presented with amenorrhoea and galactorrhoea syndrome and a complex bilateral ovarian mass. Magnetic resonance imaging revealed a pituitary adenoma, and laboratory tests corroborated the hyperprolactinaemia without other hormonal pituitary abnormalities. Ovarian hyperstimulation syndrome due to a gonadotroph adenoma with normal gonadotrophins is extremely rare. Most of the described cases are caused by FSH adenomas. Due to the originality of the case, it was considered useful for understanding the management of this entity, and it is proposed that LH adenomas should also be considered in the differential diagnosis of patients with spontaneous ovarian hyperstimulation syndrome.

  9. Luteinizing hormone induces ovulation via tumor necrosis factor α-dependent increases in prostaglandin F2α in a nonmammalian vertebrate

    PubMed Central

    Crespo, Diego; Goetz, Frederick W.; Planas, Josep V.

    2015-01-01

    Ovulation is induced by the preovulatory surge of luteinizing hormone (LH) that acts on the ovary and triggers the rupture of the preovulatory ovarian follicle by stimulating proteolysis and apoptosis in the follicle wall, causing the release of the mature oocyte. The pro-inflammatory cytokine tumor necrosis factor α (TNFα) and prostaglandin (PG) F2α (PGF2α) are involved in the control of ovulation but their role mediating the pro-ovulatory actions of LH is not well established. Here we show that Lh induces PGF2α synthesis through its stimulation of Tnfα production in trout, a primitive teleost fish. Recombinant trout Tnfα (rTnfα) and PGF2α recapitulate the stimulatory in vitro effects of salmon Lh (sLh) on contraction, proteolysis and loss of cell viability in the preovulatory follicle wall and, finally, ovulation. Furthermore, all pro-ovulatory actions of sLh are blocked by inhibition of Tnfα secretion or PG synthesis and all actions of rTnfα are blocked by PG synthesis inhibitors. Therefore, we provide evidence that the Tnfα–dependent increase in PGF2α production is necessary for the pro-ovulatory actions of Lh. The results from this study shed light onto the mechanisms underlying the pro-ovulatory actions of LH in vertebrates and may prove important in clinical assessments of female infertility. PMID:26374476

  10. Explorative solid-phase extraction (E-SPE) for accelerated microbial natural product discovery, dereplication, and purification.

    PubMed

    Månsson, Maria; Phipps, Richard K; Gram, Lone; Munro, Murray H G; Larsen, Thomas O; Nielsen, Kristian F

    2010-06-25

    Microbial natural products (NP) cover a high chemical diversity, and in consequence extracts from microorganisms are often complex to analyze and purify. A distribution analysis of calculated pK(a) values from the 34390 records in Antibase2008 revealed that within pH 2-11, 44% of all included compounds had an acidic functionality, 17% a basic functionality, and 9% both. This showed a great potential for using ion-exchange chromatography as an integral part of the separation procedure, orthogonal to the classic reversed-phase strategy. Thus, we investigated the use of an "explorative solid-phase extraction" (E-SPE) protocol using SAX, Oasis MAX, SCX, and LH-20 columns for targeted exploitation of chemical functionalities. E-SPE provides a minimum of fractions (15) for chemical and biological analyses and implicates development into a preparative scale methodology. Overall, this allows fast extract prioritization, easier dereplication, mapping of biological activities, and formulation of a purification strategy.

  11. Lateral hypothalamus, nucleus accumbens, and ventral pallidum roles in eating and hunger: interactions between homeostatic and reward circuitry

    PubMed Central

    Castro, Daniel C.; Cole, Shannon L.; Berridge, Kent C.

    2015-01-01

    The study of the neural bases of eating behavior, hunger, and reward has consistently implicated the lateral hypothalamus (LH) and its interactions with mesocorticolimbic circuitry, such as mesolimbic dopamine projections to nucleus accumbens (NAc) and ventral pallidum (VP), in controlling motivation to eat. The NAc and VP play special roles in mediating the hedonic impact (“liking”) and motivational incentive salience (“wanting”) of food rewards, and their interactions with LH help permit regulatory hunger/satiety modulation of food motivation and reward. Here, we review some progress that has been made regarding this circuitry and its functions: the identification of localized anatomical hedonic hotspots within NAc and VP for enhancing hedonic impact; interactions of NAc/VP hedonic hotspots with specific LH signals such as orexin; an anterior-posterior gradient of sites in NAc shell for producing intense appetitive eating vs. intense fearful reactions; and anatomically distributed appetitive functions of dopamine and mu opioid signals in NAc shell and related structures. Such findings help improve our understanding of NAc, VP, and LH interactions in mediating affective and motivation functions, including “liking” and “wanting” for food rewards. PMID:26124708

  12. Developmental Programming: Insulin Sensitizer Prevents the GnRH-Stimulated LH Hypersecretion in a Sheep Model of PCOS

    PubMed Central

    Cardoso, Rodolfo C.; Burns, Ashleigh; Moeller, Jacob; Skinner, Donal C.

    2016-01-01

    Prenatal testosterone (T) treatment recapitulates the reproductive and metabolic phenotypes of polycystic ovary syndrome in female sheep. At the neuroendocrine level, prenatal T treatment results in disrupted steroid feedback on gonadotropin release, increased pituitary sensitivity to GnRH, and subsequent LH hypersecretion. Because prenatal T-treated sheep manifest functional hyperandrogenism and hyperinsulinemia, gonadal steroids and/or insulin may play a role in programming and/or maintaining these neuroendocrine defects. Here, we investigated the effects of prenatal and postnatal treatments with an androgen antagonist (flutamide [F]) or an insulin sensitizer (rosiglitazone [R]) on GnRH-stimulated LH secretion in prenatal T-treated sheep. As expected, prenatal T treatment increased the pituitary responsiveness to GnRH leading to LH hypersecretion. Neither prenatal interventions nor postnatal F treatment normalized the GnRH-stimulated LH secretion. Conversely, postnatal R treatment completely normalized the GnRH-stimulated LH secretion. At the tissue level, gestational T increased pituitary LHβ, androgen receptor, and insulin receptor-β, whereas it reduced estrogen receptor (ER)α protein levels. Although postnatal F normalized pituitary androgen receptor and insulin receptor-β, it failed to prevent an increase in LHβ expression. Contrarily, postnatal R treatment restored ERα and partially normalized LHβ pituitary levels. Immunohistochemical findings confirmed changes in pituitary ERα expression to be specific to gonadotropes. In conclusion, these findings indicate that increased pituitary responsiveness to GnRH in prenatal T-treated sheep is likely a function of reduced peripheral insulin sensitivity. Moreover, results suggest that restoration of ERα levels in the pituitary may be one mechanism by which R prevents GnRH-stimulated LH hypersecretion in this sheep model of polycystic ovary syndrome-like phenotype. PMID:27792406

  13. Developmental Programming: Insulin Sensitizer Prevents the GnRH-Stimulated LH Hypersecretion in a Sheep Model of PCOS.

    PubMed

    Cardoso, Rodolfo C; Burns, Ashleigh; Moeller, Jacob; Skinner, Donal C; Padmanabhan, Vasantha

    2016-12-01

    Prenatal testosterone (T) treatment recapitulates the reproductive and metabolic phenotypes of polycystic ovary syndrome in female sheep. At the neuroendocrine level, prenatal T treatment results in disrupted steroid feedback on gonadotropin release, increased pituitary sensitivity to GnRH, and subsequent LH hypersecretion. Because prenatal T-treated sheep manifest functional hyperandrogenism and hyperinsulinemia, gonadal steroids and/or insulin may play a role in programming and/or maintaining these neuroendocrine defects. Here, we investigated the effects of prenatal and postnatal treatments with an androgen antagonist (flutamide [F]) or an insulin sensitizer (rosiglitazone [R]) on GnRH-stimulated LH secretion in prenatal T-treated sheep. As expected, prenatal T treatment increased the pituitary responsiveness to GnRH leading to LH hypersecretion. Neither prenatal interventions nor postnatal F treatment normalized the GnRH-stimulated LH secretion. Conversely, postnatal R treatment completely normalized the GnRH-stimulated LH secretion. At the tissue level, gestational T increased pituitary LHβ, androgen receptor, and insulin receptor-β, whereas it reduced estrogen receptor (ER)α protein levels. Although postnatal F normalized pituitary androgen receptor and insulin receptor-β, it failed to prevent an increase in LHβ expression. Contrarily, postnatal R treatment restored ERα and partially normalized LHβ pituitary levels. Immunohistochemical findings confirmed changes in pituitary ERα expression to be specific to gonadotropes. In conclusion, these findings indicate that increased pituitary responsiveness to GnRH in prenatal T-treated sheep is likely a function of reduced peripheral insulin sensitivity. Moreover, results suggest that restoration of ERα levels in the pituitary may be one mechanism by which R prevents GnRH-stimulated LH hypersecretion in this sheep model of polycystic ovary syndrome-like phenotype.

  14. Impairment of testicular function in adult male Japanese quail (Coturnix japonica) after a single administration of 3-methyl-4-nitrophenol in diesel exhaust particles.

    PubMed

    Li, ChunMei; Takahashi, Shinji; Taneda, Shinji; Furuta, Chie; Watanabe, Gen; Suzuki, Akira K; Taya, Kazuyoshi

    2006-06-01

    The effects of 3-methyl-4-nitrophenol (PNMC), a component of diesel exhaust, on reproductive function were investigated in adult male Japanese quail. The quail were treated with a single i.m. dose of PNMC (78, 103 or 135 mg/kg body weight), and trunk blood and testes were collected 1, 2 or 4 weeks later. Various levels of testicular atrophy were observed in all groups treated with PNMC. Sperm formation, cloacal gland area, and plasma LH and testosterone concentrations were also reduced in birds with testicular atrophy. To determine the acute effect of PNMC on gonadotrophin from the pituitary, adult male quail were administrated a single i.m. injection of PNMC (25 mg/kg), and plasma concentrations of LH were measured at 1, 3 and 6 h. This dose significantly lowered plasma levels of LH at all three time points. These results suggest that PNMC acts on the hypothalamus-pituitary axis, by reducing circulating LH within a few hours of administration and subsequently reducing testosterone secretion. In addition, in order to investigate the direct effects of PNMC on the secretion of testosterone from testicular cells in quail testes, cultured interstitial cells containing Leydig cells were exposed to PNMC (10(-6), 10(-5) or 10(-4) M) for 4, 8 or 24 h. These quantities of PNMC significantly reduced the secretion of testosterone in a time- and dose-dependent manner. The present findings also suggest a direct effect of PNMC on the testis to reduce testosterone secretion. This study clearly indicates that PNMC induces reproductive toxicity at both the central and testicular levels, and disrupts testicular function in adult male quail.

  15. Thermal Analysis on Cryogenic Liquid Hydrogen Tank on an Unmanned Aerial Vehicle System

    NASA Technical Reports Server (NTRS)

    Wang, Xiao-Yen; Harpster, George; Hunter, James

    2007-01-01

    Thermal analyses are performed on the liquid hydrogen (LH2) tank designed for an unmanned aerial vehicle (UAV) powered by solar arrays and a regenerative proton-exchange membrane (PEM) fuel cell. A 14-day cruise mission at a 65,000 ft altitude is considered. Thermal analysis provides the thermal loads on the tank system and the boiling-off rates of LH2. Different approaches are being considered to minimize the boiling-off rates of the LH2. It includes an evacuated multilayer insulation (MLI) versus aerogel insulation on the LH2 tank and aluminum versus stainless steel spacer rings between the inner and outer tank. The resulting boil-off rates of LH2 provided by the one-dimensional model and three-dimensional finite element analysis (FEA) on the tank system are presented and compared to validate the results of the three-dimensional FEA. It concludes that heat flux through penetrations by conduction is as significant as that through insulation around the tank. The tank system with MLI insulation and stainless steel spacer rings result in the lowest boiling-off rate of LH2.

  16. miR-370 regulates ISG15 expression and influences IFN-α sensitivity in hepatocellular carcinoma cells.

    PubMed

    Liu, Zhuo; Ma, Min; Yan, Lei; Chen, Shilin; Li, Sha; Yang, Darong; Wang, Xiaohong; Xiao, Hua; Deng, Hongyu; Zhu, Haizhen; Zuo, Chaohui; Xia, Man

    2018-05-05

    Interferon-α (IFN-α) is an adjuvant to chemotherapy and radiotherapy for hepatocellular carcinoma (HCC), but some HCC patients do not respond to treatment with IFN-α. We performed loss-of-function and gain-of-function experiments to examine the role of ISG15 in the IFN-α sensitivity of LH86, HLCZ01, SMMC7721, and Huh7 cell lines and tumor samples. The overexpression of ISG15 reduced apoptosis in Huh7 and LH86 cells in the presence of IFN-α, whereas the shRNA-mediated knock down of ISG15 expression increased apoptosis in both Huh7 and LH86 cells. We identified a putative miR-370 target site in the 3'-UTR in the ISG15 mRNA, and the level of miR-370 expression in HCC cell lines reflected the level of IFN-α-induced apoptosis exhibited by each. Both HCC cell lines and tumor samples had significantly lower levels of miR-370 than the control cells and tissues (P< 0.05). The overexpression of miR-370 in IFN-α-treated LH86 and Huh7 cells increased apoptosis and reduced the volume of LH86- and Huh7-derived xenograft tumors in mice treated with IFN-α compared with the control tumors. Our findings suggest that miR-370 functions as an HCC tumor suppressor and regulator of IFN-α sensitivity and that miR-370 might be a useful prognostic marker for HCC patients.

  17. LH-independent testosterone secretion is mediated by the interaction between GNRH2 and its receptor within porcine testes

    USDA-ARS?s Scientific Manuscript database

    Unlike the classical gonadotropin-releasing hormone (GNRH1), the second mammalian isoform (GNRH2) is an ineffective stimulant of gonadotropin release. Species that produce GNRH2 may not maintain a functional GNRH2 receptor (GNRHR2) due to coding errors. A full length GNRHR2 gene has been identified ...

  18. An assessment of the government liquid hydrogen requirements for the 1995-2005 time frame

    NASA Technical Reports Server (NTRS)

    Bain, Addison

    1990-01-01

    The results of government study of long range liquid hydrogen (LH2) requirements for the time period of 1995 through the year 2005 are presented. To assure an adequate supply of LH2 is available in support of various programs, it is imperative a long range projection of LH2 requirements be developed and maintained. This information is vital in planning for necessary procurement actions and assuring adequate industry lead time to acquiring the necessary production and distribution capabilities. The Advanced Launch System and High-Altitude Long-Endurance programs may represent the predominant government needs for LH2 in the long range. The assembled data clearly indicates a need for KSC (Kennedy Space Center) constant program/project surveillance. Also clear is the need for KSC to monitor industry's plans for LH2 plant production and distribution expansion.

  19. Experimental study of temperature sensor for an ocean-going liquid hydrogen (LH2) carrier

    NASA Astrophysics Data System (ADS)

    Nakano, A.; Shimazaki, T.; Sekiya, M.; Shiozawa, H.; Aoyagi, A.; Ohtsuka, K.; Iwakiri, T.; Mikami, Z.; Sato, M.; Kinoshita, K.; Matsuoka, T.; Takayama, Y.; Yamamoto, K.

    2018-04-01

    The prototype temperature sensors for an ocean-going liquid hydrogen (LH2) carrier were manufactured by way of trial. All of the sensors adopted Platinum 1000 (PT-1000) resistance thermometer elements. Various configurations of preproduction temperature sensors were tested in AIST's LH2 test facility. In the experiments, a PT-1000 resistance thermometer, calibrated at the National Metrology Institute of Japan at AIST, was used as the standard thermometer. The temperatures measured by the preproduction sensors were compared with the temperatures measured by the standard thermometer, and the measurement accuracy of the temperature sensors in LH2 was investigated and discussed. It was confirmed that the measurement accuracies of the preproduction temperature sensors were within ±50 mK, which is the required measurement accuracy for a technical demonstration ocean-going LH2 carrier.

  20. Isotopic effect in experiments on lower hybrid current drive in the FT-2 tokamak

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lashkul, S. I., E-mail: Serguey.lashkul@mail.ioffe.ru; Altukhov, A. B.; Gurchenko, A. D., E-mail: aleksey.gurchenko@mail.ioffe.ru

    To analyze factors influencing the limiting value of the plasma density at which lower hybrid (LH) current drive terminates, the isotopic factor (the difference in the LH resonance densities in hydrogen and deuterium plasmas) was used for the first time in experiments carried out at the FT-2 tokamak. It is experimentally found that the efficiency of LH current drive in deuterium plasma is appreciably higher than that in hydrogen plasma. The significant role of the parametric decay of the LH pumping wave, which hampers the use of the LH range of RF waves for current drive at high plasma densities,more » is confirmed. It is demonstrated that the parameters characterizing LH current drive agree well with the earlier results obtained at large tokamaks.« less

  1. Evaluation of biological activities of new LH-RH antagonists (T-series) in male and female rats.

    PubMed

    Pinski, J; Yano, T; Janaky, T; Nagy, A; Juhasz, A; Bokser, L; Groot, K; Schally, A V

    1993-01-01

    A series of new highly potent LH-RH antagonists (T-series) has been synthesized in our laboratory. Among these analogs, antagonists [Ac-D-Nal(2), D-Phe(4Cl)2, D-Pal(3)3, D-Lys(A2pr(Car)2)6, D-Ala10]LH-RH (T-140); [Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Lys(A2pr(Ac)2)6, D-Ala10]LH-RH (T-148); [Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Lys(A2pr(For)2)6, D-Ala10]LH-RH (T-151) and [Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Lys(A2bu(For)2)6, D-Ala10]LH-RH (T-159) were the most powerful. Antagonists T-140, T-148 and T-151 produced a complete blockade of ovulation in normal cycling rats at a dose of 1.5 micrograms/rat and antagonist T-159 at a dose of only 0.75 micrograms/rat. The inhibitory effects of compounds T-148, T-151 and T-159 on gonadotropin and sex steroid secretion were investigated in male and female rats. To determine their effect on LH levels in castrated male and ovariectomized female rats, T-148, T-151 and T-159 were injected subcutaneously in doses of 0.625 and 2.5 micrograms/rat. Blood samples were taken at different intervals for 48 h. All three compounds at either dose caused a significant (P < 0.01) decrease in LH levels for more than 6 h. Significant (P < 0.01) inhibition of LH lasted for more than 24 h following a dose of 2.5 micrograms sc of all 3 antagonists in both male and female rats. Serum FSH levels were also suppressed significantly for more than 48 h in castrated male rats by all three antagonists at a dose of 5 micrograms/rat sc.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Altered neuroendocrine regulation of gonadotropin secretion in women distance runners.

    PubMed

    Veldhuis, J D; Evans, W S; Demers, L M; Thorner, M O; Wakat, D; Rogol, A D

    1985-09-01

    We tested the hypothesis that the neuroendocrine control of gonadotropin secretion is altered in certain women distance runners with secondary amenorrhea. To this end, we quantitated the frequency and amplitude of spontaneous pulsatile LH secretion during a 24-h interval in nine such women. The ability of the pituitary gland to release LH normally was assessed by administration of graded bolus doses of GnRH during the subsequent 8 h. Compared to normally menstruating women, six of nine amenorrheic distance runners had a distinct reduction in spontaneous LH pulse frequency, with one, three, six, five, four, or two pulses per 24 h (normal, 8-15 pulses/24 h). This reduction in LH pulse frequency occurred without any significant alterations in plasma concentrations of estradiol and free testosterone or 24-h integrated serum concentrations of LH, FSH, or PRL. Moreover, in long-distance runners, the capacity of the pituitary gland to release LH was normal or accentuated in response to exogenous pulses of GnRH. In the six women athletes with diminished spontaneous LH pulsatility, acute ovarian responsiveness also was normal, since serum estradiol concentrations increased normally in response to the GnRH-induced LH pulses. Although long-distance runners had significantly lower estimated percent body fat compared to control women, specific changes in pulsatile gonadotropin release did not correlate with degree of body leanness. In summary, certain long-distance runners with secondary amenorrhea or severe oligomenorrhea have unambiguously decreased spontaneous LH pulse frequency with intact pituitary responsiveness to GnRH. This neuroendocrine disturbance may be relevant to exercise-associated amenorrhea, since pulsatile LH release is a prerequisite for cyclic ovarian function. We speculate that such alterations in pulsatile LH release in exercising women reflect an adaptive response of the hypothalamic pulse generator controlling the intermittent GnRH signal to the pituitary gland. The basis for amenorrhea in the remaining runners who have normal pulsatile properties of LH release is not known.

  3. Novel C617Y mutation in the 7th transmembrane segment of luteinizing hormone/choriogonadotropin receptor in a Japanese boy with peripheral precocious puberty.

    PubMed

    Nagasaki, Keisuke; Katsumata, Noriyuki; Ogawa, Yohei; Kikuchi, Toru; Uchiyama, Makoto

    2010-01-01

    Testotoxicosis, also known as familial male-limited precocious puberty, is an autosomal dominant form of gonadotropin-independent precocious puberty caused by heterozygous constitutively activating mutations of the LHCGR gene encoding the luteinizing hormone/choriogonadotropin receptor (LH/CGR). The patient is an 8-year-old boy who started to develop pubic hair and penile enlargement at 6 years of age. The patient had elevated serum testosterone levels, but initially exhibited a prepubertal response of gonadotropins to GnRH, which was followed by central activation of the hypothalamo-pituitary-gonadal axis. The father reported having experienced precocious puberty, and is 158 cm tall. There is no history of short stature and precocious puberty in the family except for the father. The LHCGR gene was analyzed by direct DNA sequencing of amplified PCR products from the patient and his parents. The wild-type and mutant LH/CGRs were transiently expressed in COS-1 cells and cAMP levels in the cells were determined with or without hCG stimulation. Genetic analysis revealed a novel C617Y mutation of the LHCGR gene in the patient and his mother, while his father had no mutations. Functional expression study demonstrated around 15% increase in the basal intracellular cAMP level in cells expressing the mutant LH/CGR compared with that in cells expressing the wild-type receptor. We have reported the first missense C617Y mutation located in the 7th transmembrane segment of LH/CGR causing testotoxicosis. The modest phenotype of our patient may be explained, at least in part, by the modest increase in the intracellular cAMP level caused by the C617Y mutation.

  4. Transcriptome-Based Identification of ABC Transporters in the Western Tarnished Plant Bug Lygus hesperus

    PubMed Central

    Hull, J. Joe; Chaney, Kendrick; Geib, Scott M.; Fabrick, Jeffrey A.; Brent, Colin S.; Walsh, Douglas; Lavine, Laura Corley

    2014-01-01

    ATP-binding cassette (ABC) transporters are a large superfamily of proteins that mediate diverse physiological functions by coupling ATP hydrolysis with substrate transport across lipid membranes. In insects, these proteins play roles in metabolism, development, eye pigmentation, and xenobiotic clearance. While ABC transporters have been extensively studied in vertebrates, less is known concerning this superfamily in insects, particularly hemipteran pests. We used RNA-Seq transcriptome sequencing to identify 65 putative ABC transporter sequences (including 36 full-length sequences) from the eight ABC subfamilies in the western tarnished plant bug (Lygus hesperus), a polyphagous agricultural pest. Phylogenetic analyses revealed clear orthologous relationships with ABC transporters linked to insecticide/xenobiotic clearance and indicated lineage specific expansion of the L. hesperus ABCG and ABCH subfamilies. The transcriptional profile of 13 LhABCs representative of the ABCA, ABCB, ABCC, ABCG, and ABCH subfamilies was examined across L. hesperus development and within sex-specific adult tissues. All of the transcripts were amplified from both reproductively immature and mature adults and all but LhABCA8 were expressed to some degree in eggs. Expression of LhABCA8 was spatially localized to the testis and temporally timed with male reproductive development, suggesting a potential role in sexual maturation and/or spermatozoa protection. Elevated expression of LhABCC5 in Malpighian tubules suggests a possible role in xenobiotic clearance. Our results provide the first transcriptome-wide analysis of ABC transporters in an agriculturally important hemipteran pest and, because ABC transporters are known to be important mediators of insecticidal resistance, will provide the basis for future biochemical and toxicological studies on the role of this protein family in insecticide resistance in Lygus species. PMID:25401762

  5. Docking and free energy simulations to predict conformational domains involved in hCG-LH receptor interactions using recombinant antibodies.

    PubMed

    Majumdar, Ritankar; Railkar, Reema; Dighe, Rajan R

    2011-11-01

    Single chain fragment variables (ScFvs) have been extensively employed in studying the protein-protein interactions. ScFvs derived from phage display libraries have an additional advantage of being generated against a native antigen, circumventing loss of information on conformational epitopes. In the present study, an attempt has been made to elucidate human chorionic gonadotropin (hCG)-luteinizing hormone (LH) receptor interactions by using a neutral and two inhibitory ScFvs against hCG. The objective was to dock a computationally derived model of these ScFvs onto the crystal structure of hCG and understand the differential roles of the mapped epitopes in hCG-LH receptor interactions. An anti-hCG ScFv, whose epitope was mapped previously using biochemical tools, served as the positive control for assessing the quality of docking analysis. To evaluate the role of specific side chains at the hCG-ScFv interface, binding free energy as well as residue interaction energies of complexes in solution were calculated using molecular mechanics Poisson-Boltzmann/surface area method after performing the molecular dynamic simulations on the selected hCG-ScFv models and validated using biochemical and SPR analysis. The robustness of these calculations was demonstrated by comparing the theoretically determined binding energies with the experimentally obtained kinetic parameters for hCG-ScFv complexes. Superimposition of hCG-ScFv model onto a model of hCG complexed with the 51-266 residues of LH receptor revealed importance of the residues previously thought to be unimportant for hormone binding and response. This analysis provides an alternate tool for understanding the structure-function analysis of ligand-receptor interactions. Copyright © 2011 Wiley-Liss, Inc.

  6. Persistent organic pollutants as predictors of increased FSH:LH ratio in naturally cycling, reproductive age women.

    PubMed

    Gallo, Mia V; Ravenscroft, Julia; Carpenter, David O; Schell, Lawrence M; Akwesasne Task Force On The Environment

    2018-07-01

    Although several recent studies suggest endocrine disrupting compounds, such as polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (p,p', DDE), and hexachlorobenzene (HCB), target different organs and systems in the body, their impact on female reproductive function in humans is not well characterized. We seek to determine the relationship between several known endocrine disrupting compounds and a marker of ovarian responsivity, the FSH:LH ratio (higher ratio indicates less ovarian responsivity). For this analysis, 169 naturally cycling women between 21 and 38 years of age completed interviews and had their blood drawn on day 3 of their menstrual cycle for analyses of toxicants, gonadal sex hormones (E 2 and P 4 ), and gonadotropins (FSH and LH). PCB congeners were classified into five groups based on their environmental persistence, distribution in human tissue, and toxicological action, reflecting the structure, mechanism, and known biological activity of individual PCB congeners. For every unit (ppb) increase in the level of the estrogenic PCB group, there was a 5-fold greater risk of a FSH:LH ratio ≥ 2, controlling for individual differences in age, percent body fat, cycle day 3 estradiol levels, parity, alcohol use and cigarette smoking in the past year (exp[ß] = 5; p = ≤0.01). PCB congeners identified as estrogenic were analyzed individually, and, of the 19 potentially estrogenic congeners, five were significantly, and positively related to an increased FSH:LH ratio. Four of these congeners are non-persistent, easily volatilize in the environment, and are easily metabolized, and hence, are indicative of very recent or current exposure. p,p'-DDE and HCB were not associated with FSH:LH ratio. We find a clinical indicator of ovarian responsivity, FSH:LH ratio, is associated with a specific group of estrogenic PCBs. These congeners may become airborne when they volatilize from dredged PCB-contaminated soil or from indoor PCB-containing window caulk and sealants in older buildings leading to inhalation exposure. PCB exposure, particularly to non-persistent, estrogenic congeners, may pose an unrecognized threat to female fecundity within the general population. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Morphometric analysis of the folliculostellate cells and luteinizing hormone gonadotropic cells of the anterior pituitary of the men during the aging process.

    PubMed

    Čukuranović Kokoris, Jovana; Jovanović, Ivan; Pantović, Vukica; Krstić, Miljan; Stanojković, Milica; Milošević, Verica; Ugrenović, Slađana; Stojanović, Vesna

    2017-02-01

    The aim of this research was to quantify the changes in the morphology and density of the anterior pituitary folliculostellate (FS) and luteinizing hormone (LH) cells. Material was tissue of the pituitary gland of the 14 male cadavers. Tissue slices were immunohistochemically stained with monoclonal anti-LH antibody and polyclonal anti-S100 antibody for the detection of LH and FS cells, respectively. Digital images of the stained slices were afterwards morphometrically analyzed by ImageJ. Results of the morphometric analysis showed significant increase of the FS cells volume density in cases older than 70 years. Volume density of the LH cells did not significantly change, whereas their area significantly increased with age. Nucleocytoplasmic ratio of the LH cells gradually decreased and became significant after the age of 70. Finally, volume density of the FS cell significantly correlated with LH cells area and nucleocytoplasmic ratio. From all above cited, we concluded that in men, density and size of the FS cells increase with age. Long-term hypertrophy of the LH cells results in their functional decline after the age of 70. Strong correlation between FS cells and LH cells morphometric parameters might point to age-related interaction between these two cell groups. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Different critical perinatal periods and hypothalamic sites of oestradiol action in the defeminisation of luteinising hormone surge and lordosis capacity in the rat.

    PubMed

    Sakakibara, M; Deura, C; Minabe, S; Iwata, Y; Uenoyama, Y; Maeda, K-I; Tsukamura, H

    2013-03-01

    Female rats show a gonadotrophin-releasing hormone (GnRH)/luteinising hormone (LH) surge in the presence of a preovulatory level of oestrogen, whereas males do not because of brain defeminisation during the developmental period by perinatal oestrogen converted from androgen. The present study aimed to identify the site(s) of oestrogen action and the critical period for defeminising the mechanism regulating the GnRH/LH surge. Animals given perinatal treatments, such as steroidal manipulations, brain local implantation of oestradiol (E(2) ) or administration of an NMDA antagonist, were examined for their ability to show an E(2) -induced LH surge at adulthood. Lordosis behaviour was examined to compare the mechanisms defeminising the GnRH/LH surge and sexual behaviour. A single s.c. oestradiol-benzoate administration on either the day before birth (E21), the day of birth (D0) or day 5 (D5) postpartum completely abolished the E(2) -induced LH surge at adulthood in female rats, although the same treatment did not inhibit lordosis. Perinatal castration on E21 or D0 partially rescued the E2-induced LH surge in genetically male rats, whereas castration from E21 to D5 totally rescued lordosis. Neonatal E(2) implantation in the anterior hypothalamus including the anteroventral periventricular nucleus (AVPV)/preoptic area (POA) abolished the E(2) -induced LH surge in female rats, whereas E(2) implantation in the mid and posterior hypothalamic regions had no inhibitory effect on the LH surge. Lordosis was not affected by neonatal E(2) implantation in any hypothalamic regions. In male rats, neonatal NMDA antagonist treatment rescued lordosis but not the LH surge. Taken together, these results suggest that an anterior hypothalamic region such as the AVPV/POA region is a perinatal site of oestrogen action where the GnRH/LH regulating system is defeminised to abolish the oestrogen-induced surge. The mechanism for defeminisation of the GnRH/LH surge system might be different from that of sexual behaviour, in terms of the site(s) of oestrogen action and critical period, as well as the neurotransmitter system involved. © 2012 British Society for Neuroendocrinology.

  9. Alternate-fueled transport aircraft possibilities

    NASA Technical Reports Server (NTRS)

    Aiken, W. S.

    1977-01-01

    The paper is organized to describe: (1) NASA's cryogenically fueled aircraft program; (2) LH2 subsonic and supersonic transport design possibilities (3) the fuel system and ground side problems associated with LH2 distribution; (4) a comparison of LCH4 with LH2; (5) the design possibilities for LCH4 fueled aircraft; and (6) a summary of where NASA's cryogenically fueled programs are headed.

  10. Theory and Practice in ICRF Antennas for Long Pulse Operation

    NASA Astrophysics Data System (ADS)

    Colas, L.; Faudot, E.; Brémond, S.; Heuraux, S.; Mitteau, R.; Chantant, M.; Goniche, M.; Basiuk, V.; Bosia, G.; Tore Supra Team

    2005-09-01

    Long plasma discharges on the Tore Supra (TS) tokamak were extended in 2004 towards higher powers and plasma densities by combined Lower Hybrid (LH) and Ion Cyclotron Range of Frequencies (ICRF) waves. RF pulses of 20s×8MW and 60s×4MW were produced. TS is equipped with 3 ICRF antennas, whose front faces are ready for CW operation. This paper reports on their behaviour over high power long pulses, as observed with infrared (IR) thermography and calorimetric measurements. Edge parasitic losses, although modest, are concentrated on a small surface and can raise surface temperatures close to operational limits. A complex hot spot pattern was revealed with at least 3 physical processes involved : convected power, electron acceleration in the LH near field, and a RF-specific phenomenon compatible with RF sheaths. LH coupling was also perturbed in the antenna shadow. This was attributed to RF-induced DC E×B0 convection. This motivated sheath modelling in two directions. First, the 2D topology of RF potentials was investigated in relation with the RF current distribution over the antenna, via a Green's function formalism and full-wave calculation using the ICANT code. In front of phased arrays of straps, convective cells were interpreted using the RF current profiles of strip line theory. Another class of convective cells, specific to antenna box corners, was evidenced for the first time. Within 1D sheath models assuming independent flux tubes, RF and rectified DC potentials are proportional. 2D fluid models couple nearby flux tubes via transverse polarisation currents. Unexpectedly this does not necessarily smooth RF potential maps. Peak DC potentials can even be enhanced. The experience gained on TS and the numerical tools are valuable for designing steady state high power antennas for next step devices. General rules to reduce RF potentials as well as concrete design options are discussed.

  11. Theory and Practice in ICRF Antennas for Long Pulse Operation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Colas, L.; Bremond, S.; Mitteau, R.

    2005-09-26

    Long plasma discharges on the Tore Supra (TS) tokamak were extended in 2004 towards higher powers and plasma densities by combined Lower Hybrid (LH) and Ion Cyclotron Range of Frequencies (ICRF) waves. RF pulses of 20sx8MW and 60sx4MW were produced. TS is equipped with 3 ICRF antennas, whose front faces are ready for CW operation. This paper reports on their behaviour over high power long pulses, as observed with infrared (IR) thermography and calorimetric measurements. Edge parasitic losses, although modest, are concentrated on a small surface and can raise surface temperatures close to operational limits. A complex hot spot patternmore » was revealed with at least 3 physical processes involved : convected power, electron acceleration in the LH near field, and a RF-specific phenomenon compatible with RF sheaths. LH coupling was also perturbed in the antenna shadow. This was attributed to RF-induced DC ExB0 convection. This motivated sheath modelling in two directions. First, the 2D topology of RF potentials was investigated in relation with the RF current distribution over the antenna, via a Green's function formalism and full-wave calculation using the ICANT code. In front of phased arrays of straps, convective cells were interpreted using the RF current profiles of strip line theory. Another class of convective cells, specific to antenna box corners, was evidenced for the first time. Within 1D sheath models assuming independent flux tubes, RF and rectified DC potentials are proportional. 2D fluid models couple nearby flux tubes via transverse polarisation currents. Unexpectedly this does not necessarily smooth RF potential maps. Peak DC potentials can even be enhanced. The experience gained on TS and the numerical tools are valuable for designing steady state high power antennas for next step devices. General rules to reduce RF potentials as well as concrete design options are discussed.« less

  12. Reading laterally: the cerebral hemispheric use of spatial frequencies in visual word recognition.

    PubMed

    Tadros, Karine; Dupuis-Roy, Nicolas; Fiset, Daniel; Arguin, Martin; Gosselin, Frédéric

    2013-01-04

    It is generally accepted that the left hemisphere (LH) is more capable for reading than the right hemisphere (RH). Left hemifield presentations (initially processed by the RH) lead to a globally higher error rate, slower word identification, and a significantly stronger word length effect (i.e., slower reaction times for longer words). Because the visuo-perceptual mechanisms of the brain for word recognition are primarily localized in the LH (Cohen et al., 2003), it is possible that this part of the brain possesses better spatial frequency (SF) tuning for processing the visual properties of words than the RH. The main objective of this study is to determine the SF tuning functions of the LH and RH for word recognition. Each word image was randomly sampled in the SF domain using the SF bubbles method (Willenbockel et al., 2010) and was presented laterally to the left or right visual hemifield. As expected, the LH requires less visual information than the RH to reach the same level of performance, illustrating the well-known LH advantage for word recognition. Globally, the SF tuning of both hemispheres is similar. However, these seemingly identical tuning functions hide important differences. Most importantly, we argue that the RH requires higher SFs to identify longer words because of crowding.

  13. Evaluating the Nature of So-Called S*-State Feature in Transient Absorption of Carotenoids in Light-Harvesting Complex 2 (LH2) from Purple Photosynthetic Bacteria

    PubMed Central

    2016-01-01

    Carotenoids are a class of natural pigments present in all phototrophic organisms, mainly in their light-harvesting proteins in which they play roles of accessory light absorbers and photoprotectors. Extensive time-resolved spectroscopic studies of these pigments have revealed unexpectedly complex photophysical properties, particularly for carotenoids in light-harvesting LH2 complexes from purple bacteria. An ambiguous, optically forbidden electronic excited state designated as S* has been postulated to be involved in carotenoid excitation relaxation and in an alternative carotenoid-to-bacteriochlorophyll energy transfer pathway, as well as being a precursor of the carotenoid triplet state. However, no definitive and satisfactory origin of the carotenoid S* state in these complexes has been established, despite a wide-ranging series of studies. Here, we resolve the ambiguous origin of the carotenoid S* state in LH2 complex from Rba. sphaeroides by showing that the S* feature can be seen as a combination of ground state absorption bleaching of the carotenoid pool converted to cations and the Stark spectrum of neighbor neutral carotenoids, induced by temporal electric field brought by the carotenoid cation–bacteriochlorophyll anion pair. These findings remove the need to assign an S* state, and thereby significantly simplify the photochemistry of carotenoids in these photosynthetic antenna complexes. PMID:27726397

  14. Synchronous Measurement of Ultrafast Anisotropy Decay of the B850 in Bacterial LH2 Complex

    NASA Astrophysics Data System (ADS)

    Wang, Yun-Peng; Du, Lu-Chao; Zhu, Gang-Bei; Wang, Zhuan; Weng, Yu-Xiang

    2015-02-01

    Ultrafast anisotropic decay is a prominent parameter revealing ultrafast energy and electron transfer; however, it is difficult to be determined reliably owing to the requirement of a simultaneous availability of the parallel and perpendicular polarized decay kinetics. Nowadays, any measurement of anisotropic decay is a kind of approach to the exact simultaneity. Here we report a novel method for a synchronous ultrafast anisotropy decay measurement, which can well determine the anisotropy, even at a very early time, as the rising phase of the excitation laser pulse. The anisotropic decay of the B850 in bacterial light harvesting antenna complex LH2 of Rhodobacter sphaeroides in solution at room temperature with coherent excitation is detected by this method, which shows a polarization response time of 30 fs, and the energy transfer from the initial excitation to the bacteriochlorophylls in B850 ring takes about 70 fs. The anisotropic decay that is probed at the red side of the absorption spectrum, such as 880 nm, has an initial value of 0.4, corresponding to simulated emission, while the blue side with an anisotropy of 0.1 contributes to the ground-state bleaching. Our results show that the coherent excitation covering the whole ring might not be realized owing to the symmetry breaking of LH2: from C9 symmetry in membrane to C2 symmetry in solution.

  15. Evaluating the nature of so-called S*-State feature in transient absorption of carotenoids in light-harvesting complex 2 (LH2) from purple photosynthetic bacteria

    DOE PAGES

    Niedzwiedzki, Dariusz M.; Hunter, C. Neil; Blankenship, Robert E.

    2016-10-11

    Carotenoids are a class of natural pigments present in all phototrophic organisms, mainly in their light-harvesting proteins in which they play roles of accessory light absorbers and photoprotectors. Extensive time-resolved spectroscopic studies of these pigments have revealed unexpectedly complex photophysical properties, particularly for carotenoids in light-harvesting LH2 complexes from purple bacteria. An ambiguous, optically forbidden electronic excited state designated as S* has been postulated to be involved in carotenoid excitation relaxation and in an alternative carotenoid-to-bacteriochlorophyll energy transfer pathway, as well as being a precursor of the carotenoid triplet state. However, no definitive and satisfactory origin of the carotenoid S*more » state in these complexes has been established, despite a wide-ranging series of studies. Here, we resolve the ambiguous origin of the carotenoid S* state in LH2 complex from Rba. sphaeroides by showing that the S* feature can be seen as a combination of ground state absorption bleaching of the carotenoid pool converted to cations and the Stark spectrum of neighbor neutral carotenoids, induced by temporal electric field brought by the carotenoid cation- bacteriochlorophyll anion pair. Lastly, these findings remove the need to assign an S* state, and thereby significantly simplify the photochemistry of carotenoids in these photosynthetic antenna complexes.« less

  16. Evaluating the nature of so-called S*-State feature in transient absorption of carotenoids in light-harvesting complex 2 (LH2) from purple photosynthetic bacteria

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Niedzwiedzki, Dariusz M.; Hunter, C. Neil; Blankenship, Robert E.

    Carotenoids are a class of natural pigments present in all phototrophic organisms, mainly in their light-harvesting proteins in which they play roles of accessory light absorbers and photoprotectors. Extensive time-resolved spectroscopic studies of these pigments have revealed unexpectedly complex photophysical properties, particularly for carotenoids in light-harvesting LH2 complexes from purple bacteria. An ambiguous, optically forbidden electronic excited state designated as S* has been postulated to be involved in carotenoid excitation relaxation and in an alternative carotenoid-to-bacteriochlorophyll energy transfer pathway, as well as being a precursor of the carotenoid triplet state. However, no definitive and satisfactory origin of the carotenoid S*more » state in these complexes has been established, despite a wide-ranging series of studies. Here, we resolve the ambiguous origin of the carotenoid S* state in LH2 complex from Rba. sphaeroides by showing that the S* feature can be seen as a combination of ground state absorption bleaching of the carotenoid pool converted to cations and the Stark spectrum of neighbor neutral carotenoids, induced by temporal electric field brought by the carotenoid cation- bacteriochlorophyll anion pair. Lastly, these findings remove the need to assign an S* state, and thereby significantly simplify the photochemistry of carotenoids in these photosynthetic antenna complexes.« less

  17. Preorchiectomy Leydig Cell Dysfunction in Patients With Testicular Cancer.

    PubMed

    Bandak, Mikkel; Jørgensen, Niels; Juul, Anders; Lauritsen, Jakob; Gundgaard Kier, Maria Gry; Mortensen, Mette Saksø; Daugaard, Gedske

    2017-02-01

    Little is known about preorchiectomy Leydig cell function in patients with testicular germ cell cancer (TGCC). The aim was to estimate the prevalence of preorchiectomy Leydig cell dysfunction and evaluate factors associated with this condition in a cohort of patients with TGCC. We evaluated luteinizing hormone (LH), total testosterone (TT), calculated free T (cFT), estradiol, and sex hormone-binding globulin (SHBG) preorchiectomy in 561 patients with TGCC and compared with 561 healthy controls. We calculated TT/LH and cFT/LH ratios and constructed bivariate charts of TT/LH and cFT/LH from the controls. Logistic regression analysis with an abnormal cFT/LH ratio as outcome and clinical stage, tumor size, age, histology, presence of contralateral germ cell neoplasia in situ (GCNIS), and bilateral tumors as covariates was performed. In patients who were negative for human chorionic gonadotropin (hCG) (n = 374), TT (P = .004), cFT (P < .001), TT/LH ratio (P = .003), and cFT/LH ratio (P = .002) were lower than in controls. A total of 95 (25%) and 91 (24%) of hCG-negative patients had abnormal values when using combined evaluation of TT/LH and cFT/LH, respectively. Increasing tumor size, contralateral GCNIS, and increasing age were associated with Leydig cell dysfunction. In patients positive for hCG (n = 187), all reproductive hormones except SHBG were different from controls (P < .001). Patients with TGCC are at increased risk of Leydig cell dysfunction before orchiectomy. Contralateral GCNIS, increasing age, and increasing tumor size are associated with Leydig cell dysfunction. We hypothesize that patients with preexisting Leydig cell dysfunction are at increased risk of testosterone deficiency following treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Recovery of menstruation after long-term chemotherapy and endocrine therapy in pre-menopausal patients with breast cancer.

    PubMed

    Sakurai, Kenichi; Enomoto, Katsuhisa; Amano, Sadao

    2011-04-01

    A luteinizing hormone-releasing hormone (LH-RH) agonist and tamoxifen (TAM) are used in hormonal therapy following pre- and post-operative chemotherapy in pre-menopausal advanced breast cancer patients who are positive for hormone receptors. However, it remains to be clarified how often patients recover menstruation after long-term LH-RH agonist plus TAM therapy. In this study, the incidence of menstruation recovery after therapy was examined. The subjects included 125 pre-menopausal patients with breast cancer who were positive for hormone receptors and had undergone surgery at our institution. They were treated with four cycles of the CEF regimen and four cycles of docetaxel (Doc) before surgery as adjuvant chemotherapy. Thereafter, they were treated with an LH-RH agonist plus TAM for 24 months and followed to determine menstruation recovery. Menstruation resumed in 24 cases (19.2%) after the last LH-RH agonist treatment session. It took 7.3 ± 2.8 months for the patients to recover menstruation. The rate of menstruation recovery was 42.1% in patients aged 40 or younger and 9.2% in those aged 41 or older; the difference was significant. The period until menstruation recovery tended to be longer in older patients at the end of treatment. The menstruation recovery rate after therapy was higher in younger women. However, since ovarian function may be lost even in younger patients, the potential consequences of this therapy should be fully explained beforehand to patients who may wish to become pregnant.

  19. Organophosphorus insecticide induced decrease in plasma luteinizing hormone concentration in white-footed mice

    USGS Publications Warehouse

    Rattner, B.A.; Michael, S.D.

    1985-01-01

    Oral intubation of 50 and 100 mg/kg acephate inhibited brain acetylcholinesterase (AChE) activity by 45% and 56%, and reduced basal luteinizing hormone (LH) concentration by 29% and 25% after 4 h in white-footed mice (Peromyscus leucopus noveboracensis). Dietary exposure to 25, 100, and 400 ppm acephate for 5 days substantially inhibited brain AChE activity, but did not affect plasma LH concentration. These preliminary findings suggest that acute exposure to organophosphorus insecticides may affect LH secretion and possibly reproductive function.

  20. Basic study on hot-wire flow meter in forced flow of liquid hydrogen

    NASA Astrophysics Data System (ADS)

    Oura, Y.; Shirai, Y.; Shiotsu, M.; Murakami, K.; Tatsumoto, H.; Naruo, Y.; Nonaka, S.; Kobayashi, H.; Inatani, Y.; Narita, N.

    2014-01-01

    Liquid hydrogen (LH2) is a key issue in a carbon-free energy infrastructure at the energy storage and transportation stage. The typical features of LH2 are low viscosity, large latent heat and small density, compared with other general liquids. It is necessary to measure a mass flow of liquid hydrogen with a simple and compact method, especially in a two phase separate flow condition. We have proposed applying a hot-wire type flow meter, which is usually used a for gas flow meter, to LH2 flow due to the quite low viscosity and density. A test model of a compact LH2 hot-wire flow meter to measure local flow velocities near and around an inside perimeter of a horizontal tube by resistance thermometry was designed and made. The model flow meter consists of two thin heater wires made of manganin fixed in a 10 mm-diameter and 40 mm-length tube flow path made of GFRP. Each rigid heater wire was set twisted by 90 degrees from the inlet to the outlet along the inner wall. In other words, the wires were aslant with regard to the LH2 stream line. The heated wire was cooled by flowing LH2, and the flow velocity was obtained by means of the difference of the cooling characteristic in response to the flow velocity. In this report, we show results on the basic experiments with the model LH2 hot-wire flow meter. First, the heat transfer characteristics of the two heater wires for several LH2 flow velocities were measured. Second, the heating current was controlled to keep the wire temperature constant for various flow velocities. The relations between the flow velocity and the heating current were measured. The feasibility of the proposed model was confirmed.

  1. [The method of tonifying kidneys and activating blood circulation increases testosterone secretion index in late-onset hypogonadism males with kidney deficiency].

    PubMed

    Zhou, Shao-Hu; Weng, Zhi-Wei; Li, Tang-Lin

    2013-07-01

    To investigate the effect of the method of tonifying the kidney and activating blood circulation on the testosterone secretion index (TSI) in late-onset hypogonadism (LOH) male patients with kidney deficiency and its possible mechanisms. We screened 60 LOH male patients with kidney deficiency based on the scores on Partial Androgen Deficiency in Aging Males (PADAM), the levels of serum total testosterone (TT) and luteinizing hormone (LH), and TSI (TT/LH). We randomly divided the patients into a Nan Geng Ning (NGN) group (n = 40, aged 55.02 +/- 11.37 years) and a control group (n = 20, aged 54.56 +/- 12.12 years) to be treated orally with NGN decoction and testosterone undecanoate capsules, respectively, both for 12 consecutive weeks. We obtained the scores on psychological status, physical status and sexual function and observed the changes in serum TT, LH and TSI after 4, 8 and 12 weeks of treatment. Compared with the baseline, both the NGN and control groups showed a significant reduction after 12 weeks of medication in the LH level ([5.32 +/- 2.08] vs [4.89 +/- 1.46] IU/L and [5.36 +/- 2.07] vs [4.81 +/- 1.75] IU/L, P < 0.05), psychological status score (5.2 +/- 1.3 vs 2.7 +/- 1.4 and 4.8 +/- 2.2 vs 2.9 +/- 1.2, P < 0.05), physical status score (6.9 +/- 2.5 vs 2.9 +/- 1.6 and 7.1 +/- 2.7 vs 3.1 +/- 1.5, P < 0.05) and sexual function score (10.2 +/- 3.3 vs 4.5 +/- 2.9 and 9.8 +/- 3.1 vs 4.8 +/- 3.0, P < 0.05), but a remarkable increase in the TT level ([11.13 +/- 0.69] vs [14.55 +/- 0.75] nmol/L and [10.99 +/- 0.74] vs [14.74 +/- 0.83] nmol/L, P < 0.05) and TSI ([2.14 +/- 0.65] vs [2.99 +/- 0.72] nmol/IU and ([2.05 +/- 0.73] vs [3.11 +/- 0.65] nmol/IU, P < 0.05). However, no significant differences were found between the NGN and control groups at 12 weeks in LH ([4.89 +/- 1.46] vs [4.81 +/- 1.75] IU/L, P > 0.05), TT ([14.55 +/- 0.75] vs [14.74 +/- 0.83] nmol/L, P > 0.05), TSI ([2.99 +/- 0.72] vs [3.11 +/- 0.65] nmol/IU, P > 0.05), psychological status score (2.7 +/- 1.4 vs 2.9 +/- 1.2, P > 0.05), physi- cal status score (2.9 +/- 1.6 vs 3.1 +/- 1.5, P > 0.05) and sexual function score (4.5 +/- 2.9 vs 4.8 +/- 3.0, P > 0.05). There were no adverse events in either of the two groups throughout the whole experiment. The method of tonifying the kidney and activating blood circulation could significantly improve the clinical symptoms of LOH with kidney deficiency and increase the patient's serum TT level and TSI. NGN decoction works on LOH by acting on the hypothalamic-pituitary-gonad axis.

  2. The use of hydrogen for aircraft propulsion in view of the fuel crisis

    NASA Technical Reports Server (NTRS)

    Weiss, S.

    1973-01-01

    Some factors influencing the technical feasibility of operating a liquid hydrogen-fueled airplane are discussed in light of the projected decrease of fossil fuels. Other sources of energy, such as wind, tidal, solar, and geothermal, are briefly mentioned. In view of projected decreases in available petroleum fuels, interest has been generated in exploiting the potential of liquid hydrogen (LH2) as an aircraft fuel. Cost studies of LH2 production show it to be more expensive than presently used fuels. Regardless of cost considerations, LH2 is viewed as an attractive aircraft fuel because of the potential performance benefits it offers. Accompanying these benefits, however, are many new problems associated with aircraft design and operations; for example, problems related to fuel system design and the handling of LH2 during ground servicing. Some of the factors influencing LH2 fuel tank design, pumping, heat exchange, and flow regulation are discussed.

  3. A history of the UK liquid hydrogen programme

    NASA Astrophysics Data System (ADS)

    Harlow, J.

    1992-07-01

    A review is presented of the evolution of UK liquid hydrogen (LH2) programs into the testing of low- and higher-pressure engines for upper stage applications with attention given to the production of LH2. The engine requirements are examined of launchers such as the Black Knight and Black Prince vehicles and LOX/LH2 upper stages for the European Launcher Development Organization (ELDO). High-energy second and third stages are described for the ELDO vehicles, and injector types and thrust-chamber designs are illustrated for the use of LH2/LOX. Successful firings of the RZ-20 chamber are reported, and the production of liquid hydrogen is shown to be adequate for testing and usage over all of the experimental phases. Developments from the LH2 programs in the UK can provide technologies for current items such as the propellant feed lines for the Ariane program.

  4. Some early perspectives on ground requirements of liquid hydrogen air transports

    NASA Technical Reports Server (NTRS)

    Korycinski, P. F.

    1976-01-01

    The paper examines the problem of liquid-hydrogen (LH2) subsonic long-range air transport from the perspectives of airplane manufacturers, the airline operator, the air terminal authority and the LH2 supplier. Emphasis is placed on identifying common problems and interfaces that are likely to occur in preparing for commercial airline operations of LH2 subsonic air transport in the 1990-1995 period. General considerations are discussed relative to sources and cost of gaseous hydrogen, hydrogen liquefaction, and LH2 availability. The fact that hydrogen sustains combustion at altitudes substantially higher than hydrocarbon fuels suggests that air transport can be designed to operate at higher enroute air traffic flight levels. This can be an advantage if only to relieve traffic congestion on heavily traveled routes. Pertinent interfaces in planning for the use of LH2 in air transportation are identified, including productivity and profitability, passenger-fuel compatibility, and lightning and electrical discharges.

  5. Theory of Excitonic Delocalization for Robust Vibronic Dynamics in LH2.

    PubMed

    Caycedo-Soler, Felipe; Lim, James; Oviedo-Casado, Santiago; van Hulst, Niek F; Huelga, Susana F; Plenio, Martin B

    2018-06-11

    Nonlinear spectroscopy has revealed long-lasting oscillations in the optical response of a variety of photosynthetic complexes. Different theoretical models that involve the coherent coupling of electronic (excitonic) or electronic-vibrational (vibronic) degrees of freedom have been put forward to explain these observations. The ensuing debate concerning the relevance of either mechanism may have obscured their complementarity. To illustrate this balance, we quantify how the excitonic delocalization in the LH2 unit of Rhodopseudomonas acidophila purple bacterium leads to correlations of excitonic energy fluctuations, relevant coherent vibronic coupling, and importantly, a decrease in the excitonic dephasing rates. Combining these effects, we identify a feasible origin for the long-lasting oscillations observed in fluorescent traces from time-delayed two-pulse single-molecule experiments performed on this photosynthetic complex and use this approach to discuss the role of this complementarity in other photosynthetic systems.

  6. The Use of rLH, HMG and hCG in Controlled Ovarian Stimulation for Assisted Reproductive Technologies

    DTIC Science & Technology

    2012-11-21

    express CYP17, the gene encoding for the critical enzyme in the conversion of progesterone and pregnenalone to androgens (3). Conversely, granulosa...2. Potential mechanisms of exogenous LH benefit in ART There are theoretical benefits of the use of exogenous LH for the oocyte and the endometrium...folliculogenesis when administered with FSH (85). rLH has potential advantages over the LH activity in hMG in that there is less risk of protein contamination and

  7. Hypothalamic expression of KiSS-1 system and gonadotropin-releasing effects of kisspeptin in different reproductive states of the female Rat.

    PubMed

    Roa, J; Vigo, E; Castellano, J M; Navarro, V M; Fernández-Fernández, R; Casanueva, F F; Dieguez, C; Aguilar, E; Pinilla, L; Tena-Sempere, M

    2006-06-01

    Kisspeptins, products of the KiSS-1 gene with ability to bind G protein-coupled receptor 54 (GPR54), have been recently identified as major gatekeepers of reproductive function with ability to potently activate the GnRH/LH axis. Yet, despite the diversity of functional states of the female gonadotropic axis, pharmacological characterization of this effect has been mostly conducted in pubertal animals or adult male rodents, whereas similar studies have not been thoroughly conducted in the adult female. In this work, we evaluated maximal LH and FSH secretory responses to kisspeptin-10, as well as changes in sensitivity and hypothalamic expression of KiSS-1 and GPR54 genes, in different physiological and experimental models in the adult female rat. Kisspeptin-10 (1 nmol, intracerebroventricular) was able to elicit robust LH bursts at all phases of the estrous cycle, with maximal responses at estrus; yet, in diestrus LH, responses to kisspeptin were detected at doses as low as 0.1 pmol. In contrast, high doses of kisspeptin only stimulated FSH secretion at diestrus. Removal of ovarian sex steroids did not blunt the ability of kisspeptin to further elicit stimulated LH and FSH secretion, but restoration of maximal responses required replacement with estradiol and progesterone. Finally, despite suppressed basal levels, LH and FSH secretory responses to kisspeptin were preserved in pregnant and lactating females, although the magnitude of LH bursts and the sensitivity to kisspeptin were much higher in pregnant dams. Interestingly, hypothalamic KiSS-1 gene expression significantly increased during pregnancy, whereas GPR54 mRNA levels remained unaltered. In summary, our current data document for the first time the changes in hypothalamic expression of KiSS-1 system and the gonadotropic effects (maximal responses and sensitivity) of kisspeptin in different functional states of the female reproductive axis. The present data may pose interesting implications in light of the potential therapeutic use of kisspeptin analogs in the pharmacological manipulation of the gonadotropic axis in the female.

  8. Cooling Stability Test of MgB2 Wire Immersed in Liquid Hydrogen under External Magnetic Field

    NASA Astrophysics Data System (ADS)

    Shirai, Yasuyuki; Hikawa, Kyosuke; Shiotsu, Masahiro; Tatsumoto, Hideki; Naruo, Yoshihiro; Kobayashi, Hiroaki; Inagaki, Yoshifumi

    2014-05-01

    Liquid hydrogen (LH2), which has large latent heat, low viscosity coefficient, is expected to be a candidate for a cryogen for superconducting wires, not only MgB2 but also other HTC superconductors. LH2 cooled superconducting wires are expected to have excellent electro-magnetic characteristics, which is necessary to be clear for cooling stability design of LH2 cooled superconducting device, however, due to handling difficulties of LH2, there are only few papers on the properties of LH2 cooled superconductors, especially under external magnetic field. We designed and made an experimental setup which can energize superconducting wires immersed in LH2 with the current of up to 500A under the condition of external magnetic field up to 7 T and pressure up to 1.5 MPa. In order to confirm experimental method and safety operation of the setup, over current tests were carried out using MgB2 superconducting wires under various external magnetic field conditions. Critical current of the test wire at the temperature 21, 24, 27, 29 K under external magnetic fields up to 1.2 T was successfully measured. The resistance of the wire also was measured, while the transport current exceeded the critical current of the wire.

  9. Impaired sexual maturation associated with sleep apnea syndrome during puberty: a case study.

    PubMed

    Mosko, S S; Lewis, E; Sassin, J F

    1980-01-01

    A 20-year-old hypogonadal man was discovered to have had obstructive sleep apnea syndrome--secondary to hypertrophied tonsils, adenoids, and uvula--spanning the years of puberty. All-night polysomnographic recordings and 24 hr measurements of plasma luteinizing hormone (LH) concentrations (sampling at 20 min intervals) were performed before and after combined tonsillectomy, adenoidectomy, and uvulectomy. Two weeks preoperatively, nocturnal sleep was markedly disturbed by 407 apneic episodes, and the patient was found to be hypogonadotropic. Daytime LH concentrations were in the low-normal range for an adult male, and concentrations fell dramatically during nocturnal sleep. This contrasts with both the sleep-related elevation of LH normally seen in puberty and the adult pattern, where no difference is observed in mean concentrations during waking and sleep. Two week and 6 month postoperative evaluations revealed complete alleviation of the sleep apnea syndrome and normalization of the 24 hr pattern of plasma LH, although LH values remained in the low-normal range. Plasma testosterone concentrations were in the low to low-normal range both pre- and postoperatively. No evidence of continued sexual development, beyond that achieved preoperatively, was observed 20 months after surgery, despite continued relief from apnea. These data suggest that sleep apnea during puberty may impair sexual development by preventing the sleep-related elevation in LH secretion normally observed during a critical period spanning puberty.

  10. Crucial role of dynamic linker histone binding and divalent ions for DNA accessibility and gene regulation revealed by mesoscale modeling of oligonucleosomes

    PubMed Central

    Collepardo-Guevara, Rosana; Schlick, Tamar

    2012-01-01

    Monte Carlo simulations of a mesoscale model of oligonucleosomes are analyzed to examine the role of dynamic-linker histone (LH) binding/unbinding in high monovalent salt with divalent ions, and to further interpret noted chromatin fiber softening by dynamic LH in monovalent salt conditions. We find that divalent ions produce a fiber stiffening effect that competes with, but does not overshadow, the dramatic softening triggered by dynamic-LH behavior. Indeed, we find that in typical in vivo conditions, dynamic-LH binding/unbinding reduces fiber stiffening dramatically (by a factor of almost 5, as measured by the elasticity modulus) compared with rigidly fixed LH, and also the force needed to initiate chromatin unfolding, making it consistent with those of molecular motors. Our data also show that, during unfolding, divalent ions together with LHs induce linker-DNA bending and DNA–DNA repulsion screening, which guarantee formation of heteromorphic superbeads-on-a-string structures that combine regions of loose and compact fiber independently of the characteristics of the LH–core bond. These structures might be important for gene regulation as they expose regions of the DNA selectively. Dynamic control of LH binding/unbinding, either globally or locally, in the presence of divalent ions, might constitute a mechanism for regulation of gene expression. PMID:22790986

  11. Direct Visualization of Exciton Reequilibration in the LH1 and LH2 Complexes of Rhodobacter sphaeroides by Multipulse Spectroscopy

    PubMed Central

    Cohen Stuart, Thomas A.; Vengris, Mikas; Novoderezhkin, Vladimir I.; Cogdell, Richard J.; Hunter, C. Neil; van Grondelle, Rienk

    2011-01-01

    The dynamics of the excited states of the light-harvesting complexes LH1 and LH2 of Rhodobacter sphaeroides are governed, mainly, by the excitonic nature of these ring-systems. In a pump-dump-probe experiment, the first pulse promotes LH1 or LH2 to its excited state and the second pulse dumps a portion of the excited state. By selective dumping, we can disentangle the dynamics normally hidden in the excited-state manifold. We find that by using this multiple-excitation technique we can visualize a 400-fs reequilibration reflecting relaxation between the two lowest exciton states that cannot be directly explored by conventional pump-probe. An oscillatory feature is observed within the exciton reequilibration, which is attributed to a coherent motion of a vibrational wavepacket with a period of ∼150 fs. Our disordered exciton model allows a quantitative interpretation of the observed reequilibration processes occurring in these antennas. PMID:21539791

  12. Direct visualization of exciton reequilibration in the LH1 and LH2 complexes of Rhodobacter sphaeroides by multipulse spectroscopy.

    PubMed

    Cohen Stuart, Thomas A; Vengris, Mikas; Novoderezhkin, Vladimir I; Cogdell, Richard J; Hunter, C Neil; van Grondelle, Rienk

    2011-05-04

    The dynamics of the excited states of the light-harvesting complexes LH1 and LH2 of Rhodobacter sphaeroides are governed, mainly, by the excitonic nature of these ring-systems. In a pump-dump-probe experiment, the first pulse promotes LH1 or LH2 to its excited state and the second pulse dumps a portion of the excited state. By selective dumping, we can disentangle the dynamics normally hidden in the excited-state manifold. We find that by using this multiple-excitation technique we can visualize a 400-fs reequilibration reflecting relaxation between the two lowest exciton states that cannot be directly explored by conventional pump-probe. An oscillatory feature is observed within the exciton reequilibration, which is attributed to a coherent motion of a vibrational wavepacket with a period of ∼150 fs. Our disordered exciton model allows a quantitative interpretation of the observed reequilibration processes occurring in these antennas. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  13. Bifurcation analysis and dimension reduction of a predator-prey model for the L-H transition

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dam, Magnus; Brøns, Morten; Juul Rasmussen, Jens

    2013-10-15

    The L-H transition denotes a shift to an improved confinement state of a toroidal plasma in a fusion reactor. A model of the L-H transition is required to simulate the time dependence of tokamak discharges that include the L-H transition. A 3-ODE predator-prey type model of the L-H transition is investigated with bifurcation theory of dynamical systems. The analysis shows that the model contains three types of transitions: an oscillating transition, a sharp transition with hysteresis, and a smooth transition. The model is recognized as a slow-fast system. A reduced 2-ODE model consisting of the full model restricted to themore » flow on the critical manifold is found to contain all the same dynamics as the full model. This means that all the dynamics in the system is essentially 2-dimensional, and a minimal model of the L-H transition could be a 2-ODE model.« less

  14. Reversal of idiopathic hypogonadotropic hypogonadism: a cohort study in Chinese patients

    PubMed Central

    Mao, Jiang-Feng; Xu, Hong-Li; Duan, Jin; Chen, Rong-Rong; Li, Li; Li, Bin; Nie, Min; Min, Le; Zhang, Hong-Bing; Wu, Xue-Yan

    2015-01-01

    Although idiopathic hypogonadotropic hypogonadism (IHH) has traditionally been viewed as a life-long disease caused by a deficiency of gonadotropin-releasing hormone neurons, a portion of patients may gradually regain normal reproductive axis function during hormonal replacement therapy. The predictive factors for potential IHH reversal are largely unknown. The aim of our study was to investigate the incidence and clinical features of IHH male patients who had reversed reproductive axis function. In this retrospective cohort study, male IHH patients were classified into a reversal group (n = 18) and a nonreversal group (n = 336). Concentration of gonadotropins and testosterone, as well as testicle sizes and sperm counts, were determined. Of 354 IHH patients, 18 (5.1%) acquired normal reproductive function during treatment. The median age for reversal was 24 years old (range 21–34 years). Compared with the nonreversal group, the reversible group had higher basal luteinizing hormone (LH) (1.0 ± 0.7 IU l-1 vs 0.4 ± 0.4 IU l−1, P < 0.05) and stimulated LH (28.3 ± 22.6 IU l−1 vs 1.9 ± 1.1 IU l−1, P < 0.01) levels, as well as larger testicle size (5.1 ± 2.6 ml vs 1.5 ± 0.3 ml, P < 0.01), at the initial visit. In summary, larger testicle size and higher stimulated LH concentrations are favorite parameters for reversal. Our finding suggests that reversible patients may retain partially active reproductive axis function at initial diagnosis. PMID:25578938

  15. Environment-assisted Quantum Critical Effect for Excitation Energy Transfer in a LH2-type Trimer

    NASA Astrophysics Data System (ADS)

    Xu, Lan; Xu, Bo

    2015-10-01

    In this article, we are investigating excitation energy transfer (EET) in a basic unit cell of light-harvesting complex II (LH2), named a LH2-type trimer. Calculation of energy transfer efficiency (ETE) in the framework of non-Markovian environment is also implemented. With these achievements, we theoretically predict the environment-assisted quantum critical effect, where ETE exhibits a sudden change at the critical point of quantum phase transition (QPT) for the LH2-type trimer. It is found that highly efficient EET with nearly unit efficiency may occur in the vicinity of the critical point of QPT.

  16. Triplet Excitation Transfer between Carotenoids in the LH2 Complex from Photosynthetic Bacterium Rhodopseudomonas palustris.

    PubMed

    Feng, Juan; Wang, Qian; Wu, Yi-Shi; Ai, Xi-Cheng; Zhang, Xu-Jia; Huang, You-Guo; Zhang, Xing-Kang; Zhang, Jian-Ping

    2004-01-01

    We have studied, by means of sub-microsecond time-resolved absorption spectroscopy, the triplet-excited state dynamics of carotenoids (Cars) in the intermediate-light adapted LH2 complex (ML-LH2) from Rhodopseudomonas palustris containing Cars with different numbers of conjugated double bonds. Following pulsed photo-excitation at 590 nm at room temperature, rapid spectral equilibration was observed either as a red shift of the isosbestic wavelength on a time scale of 0.6-1.0 mus, or as a fast decay in the shorter-wavelength side of the T(n)<--T(1) absorption of Cars with a time constant of 0.5-0.8 mus. Two major spectral components assignable to Cars with 11 and 12 conjugated double bonds were identified. The equilibration was not observed in the ML-LH2 at 77 K, or in the LH2 complex from Rhodobacter sphaeroides G1C containing a single type of Car. The unique spectral equilibration was ascribed to temperature-dependent triplet excitation transfer among different Car compositions. The results suggest that Cars of 11 and 12 conjugated bonds, both in close proximity of BChls, may coexist in an alpha,beta-subunit of the ML-LH2 complex.

  17. Whole brain-pituitary in vitro preparation of the transgenic medaka (Oryzias latipes) as a tool for analyzing the differential regulatory mechanisms of LH and FSH release.

    PubMed

    Karigo, Tomomi; Aikawa, Masato; Kondo, Chika; Abe, Hideki; Kanda, Shinji; Oka, Yoshitaka

    2014-02-01

    Two types of gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), are important pituitary hormones for sexual maturation and reproduction, and both of them are centrally regulated by gonadotropin-releasing hormone (GnRH) from the hypothalamus. In mammals, these two gonadotropins are secreted from a single type of gonadotrope. The mechanisms of differential regulation by GnRH of the release of two types of gonadotropins with different secretory profiles are still unknown. In teleosts, however, LH and FSH are secreted from separate cellular populations, unlike in mammals. This feature makes them useful for studying the regulatory mechanisms of LH and FSH secretions independently. Here, we generated transgenic medaka lines that express Ca(2+) indicator protein, inverse-pericam, specifically in the LH or FSH cells. We performed cell-type-specific Ca(2+) imaging of LH and FSH cells, respectively, using the whole brain-pituitary preparations of these transgenic fish in which all neural circuits and GnRH neuronal projection to the pituitary are kept intact. LH and FSH cells showed different Ca(2+) responses to GnRH. The results suggest differential regulation mechanisms for LH and FSH release by GnRH. Moreover, we also succeeded in detecting the effect on LH cells of endogenous GnRH peptide, which was released by electrical stimulation of the axons of GnRH1 neurons. Thus, our newly developed experimental model system using the whole brain-pituitary in vitro preparation of the transgenic medaka is a powerful tool for analyzing the differential regulatory mechanisms of the release of LH and FSH by multisynaptic neural inputs to the pituitary.

  18. Solar Thermal Upper Stage Cryogen System Engineering Checkout Test

    NASA Technical Reports Server (NTRS)

    Olsen, A. D; Cady, E. C.; Jenkins, D. S.

    1999-01-01

    The Solar Thermal Upper Stage technology (STUSTD) program is a solar thermal propulsion technology program cooperatively sponsored by a Boeing led team and by NASA MSFC. A key element of its technology program is development of a liquid hydrogen (LH2) storage and supply system which employs multi-layer insulation, liquid acquisition devices, active and passive thermodynamic vent systems, and variable 40W tank heaters to reliably provide near constant pressure H2 to a solar thermal engine in the low-gravity of space operation. The LH2 storage and supply system is designed to operate as a passive, pressure fed supply system at a constant pressure of about 45 psia. During operation of the solar thermal engine over a small portion of the orbit the LH2 storage and supply system propulsively vents through the enjoy at a controlled flowrate. During the long coast portion of the orbit, the LH2 tank is locked up (unvented). Thus, all of the vented H2 flow is used in the engine for thrust and none is wastefully vented overboard. The key to managing the tank pressure and therefore the H2 flow to the engine is to manage and balance the energy flow into the LH2 tank with the MLI and tank heaters with the energy flow out of the LH2 tank through the vented H2 flow. A moderate scale (71 cu ft) LH2 storage and supply system was installed and insulated at the NASA MSFC Test Area 300. The operation of the system is described in this paper. The test program for the LH2 system consisted of two parts: 1) a series of engineering tests to characterize the performance of the various components in the system: and 2) a 30-day simulation of a complete LEO and GEO transfer mission. This paper describes the results of the engineering tests, and correlates these results with analytical models used to design future advanced Solar Orbit Transfer Vehicles.

  19. Apo-bacteriophytochromes modulate bacterial photosynthesis in response to low light.

    PubMed

    Fixen, Kathryn R; Baker, Anna W; Stojkovic, Emina A; Beatty, J Thomas; Harwood, Caroline S

    2014-01-14

    Bacteriophytochromes (BphPs) are light-sensing regulatory proteins encoded by photosynthetic and nonphotosynthetic bacteria. This protein class has been characterized structurally, but its biological activities remain relatively unexplored. Two BphPs in the anoxygenic photosynthetic bacterium Rhodopseudomonas palustris, designated regulatory proteins RpBphP2 and RpBphP3, are configured as light-regulated histidine kinases, which initiate a signal transduction system that controls expression of genes for the low light harvesting 4 (LH4) antenna complex. In vitro, RpBphP2 and RpBphP3 respond to light quality by reversible photoconversion, a property that requires the light-absorbing chromophore biliverdin. In vivo, RpBphP2 and RpBphP3 are both required for the expression of the LH4 antenna complex under anaerobic conditions, but biliverdin requires oxygen for its synthesis by heme oxygenase. On further investigation, we found that the apo-bacteriophytochrome forms of RpBphP2 and RpBphP3 are necessary and sufficient to control LH4 expression in response to light intensity in conjunction with other signal transduction proteins. One possibility is that the system senses a reduced quinone pool generated when light energy is absorbed by bacteriochlorophyll. The biliverdin-bound forms of the BphPs have the additional property of being able to fine-tune LH4 expression in response to light quality. These observations support the concept that some bacteriophytochromes can function with or without a chromophore and may be involved in regulating physiological processes not directly related to light sensing.

  20. First experiment on liquid hydrogen transportation by ship inside Osaka bay

    NASA Astrophysics Data System (ADS)

    Maekawa, K.; Takeda, M.; Hamaura, T.; Suzuki, K.; Miyake, Y.; Matsuno, Y.; Fujikawa, S.; Kumakura, H.

    2017-12-01

    A project to import a large amount of liquid hydrogen (LH2) from Australia by a cargo carrier, which is equipped with two 1250 m3 tanks, is underway in Japan. It is important to understand sloshing and boil-off characteristics inside the LH2 tank during marine transportation. However, the LH2 sloshing and boil-off characteristics on the sea have not yet been clarified. First experiment on the LH2 transportation of 20 liter with magnesium diboride (MgB2) level sensors by the training ship “Fukae-maru”, which has 50 m long and 449 ton gross weight, was carried out successfully inside Osaka bay on February 2, 2017. In the experiment, synchronous measurements of liquid level, temperature, pressure, ship motions, and accelerations as well as the rapid depressurization test were done. The increase rate of the temperature and the pressure inside the LH2 tank were discussed under the rolling and the pitching conditions.

  1. Expression of the androgen receptor in the testes and the concentrations of gonadotropins and sex steroid hormones in male turkeys (Meleagris gallopavo) during growth and development.

    PubMed

    Kiezun, J; Leska, A; Kaminska, B; Jankowski, J; Dusza, L

    2015-04-01

    Androgens, including testosterone (T) and androstenedione (A4), are essential for puberty, fertility and sexual functions. The biological activity of those hormones is mediated via the androgen receptor (AR). The regulation of androgen action in birds is poorly understood. Therefore, the present study analysed mRNA and protein expression of AR in the testes, plasma concentrations of the luteinizing hormone (LH), follicle-stimulating hormone (FSH), T, A4 and oestradiol (E2), as well as the levels of T, A4 and E2 in testicular homogenates of male turkeys (Meleagris gallopavo) at the age of 4, 8, 12, 16, 20, 24 and 28weeks. Plasma concentrations of LH and FSH, as well as plasma and testicular levels of T and A4 began to increase at 20weeks of age. The lowest plasma levels of E2 were noted at 20weeks relative to other growth stages. The 20th week of life seems to be the key phase in the development of the reproductive system of turkeys. The AR protein was found in the nuclei of testicular cells in all examined growth stages. Higher expression of AR protein in the testes beginning at 20weeks of age was accompanied by high plasma concentrations of LH and high plasma and testicular levels of androgens. This relationship seems to be necessary to regulate male sexual function. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Probing the Role of Nascent Helicity in p27 Function as a Cell Cycle Regulator

    PubMed Central

    Otieno, Steve; Kriwacki, Richard

    2012-01-01

    p27 regulates the activity of Cdk complexes which are the principal governors of phase transitions during cell division. Members of the p27 family of proteins, which also includes p21 and p57, are called the Cip/Kip cyclin-dependent kinase regulators (CKRs). Interestingly, the Cip/Kip CKRs play critical roles in cell cycle regulation by being intrinsically unstructured, a characteristic contrary to the classical structure-function paradigm. They exhibit nascent helicity which has been localized to a segment referred to as sub-domain LH. The nascent helicity of this sub-domain is conserved and we hypothesize that it is an important determinant of their functional properties. To test this hypothesis, we successfully designed and prepared p27 variants in which domain LH was either more or less helical with respect to the wild-type protein. Thermal denaturation experiments showed that the ternary complexes of the p27 variants bound to Cdk2/Cyclin A were less stable compared to the wild-type complex. Isothermal titration calorimetry experiments showed a decrease in the enthalpy of binding for all the mutants with respect to p27. The free energies of binding varied within a much narrower range. In vitro Cdk2 inhibition assays showed that the p27 variants exhibited disparate inhibitory potencies. Furthermore, when over-expressed in NIH 3T3 mouse fibroblast cells, the less helical p27 variants were less effective in causing cell cycle arrest relative to the wild-type p27. Our results indicate that the nascent helicity of sub-domain LH plays a key role mediating the biological function of p27. PMID:23071750

  3. Repeated administration of CGP 46381, a gamma-aminobutyric acidB antagonist, and ethosuximide suppresses seizure-associated cyclic adenosine 3'5' monophosphate response element- and activator protein-1 DNA-binding activities in lethargic (lh/lh) mice.

    PubMed

    Ishige, K; Endo, H; Saito, H; Ito, Y

    2001-01-19

    To characterize seizure-associated increases in cerebral cortical and thalamic cyclic AMP responsive element (CRE)- and activator protein 1 (AP-1) DNA-binding activities in lethargic (lh/lh) mice, a genetic model of absence seizures, we examined the effects of ethosuximide and CGP 46381 on these DNA-binding activities. Repeated administration (twice a day for 5 days) of ethosuximide (200 mg/kg) or CGP 46381 (60 mg/kg) attenuated both seizure behavior and the increased DNA-binding activities, and was more effective than a single administration of these drugs. These treatments did not affect either normal behavior or basal DNA-binding activities in non-epileptic control (+/+) mice. Gel supershift assays revealed that the increased CRE-binding activity was attributable to activation of the binding activity of CREB, and that the c-Fos-c-Jun complex was a component of the increased AP-1 DNA-binding activity.

  4. EFFECTS OF BROMODICHLOROMETHANE ON EX VIVO AND IN VITRO LUTEAL FUNCTION AND BROMODICHLOROMETHANE TISSUE DOSIMETRY IN THE PREGNANT F344 RAT

    EPA Science Inventory

    Bromodichloromethane (BDCM), a drinking water disinfection by-product, causes pregnancy loss, i.e. full-litter resorption, in F344 rats when treated during the luteinizing hormone (LH)-dependent period. This effect is associated with reduced maternal serum progesterone (P) and LH...

  5. X-Rays from the Location of the Double-humped Transient ASASSN-15lh

    NASA Astrophysics Data System (ADS)

    Margutti, R.; Metzger, B. D.; Chornock, R.; Milisavljevic, D.; Berger, E.; Blanchard, P. K.; Guidorzi, C.; Migliori, G.; Kamble, A.; Lunnan, R.; Nicholl, M.; Coppejans, D. L.; Dall'Osso, S.; Drout, M. R.; Perna, R.; Sbarufatti, B.

    2017-02-01

    We present the detection of persistent soft X-ray radiation with {L}x˜ {10}41-1042 erg s-1 at the location of the extremely luminous, double-humped transient ASASSN-15lh as revealed by Chandra and Swift. We interpret this finding in the context of observations from our multiwavelength campaign, which revealed the presence of weak narrow nebular emission features from the host-galaxy nucleus and clear differences with respect to superluminous supernova optical spectra. Significant UV flux variability on short timescales detected at the time of the rebrightening disfavors the shock interaction scenario as the source of energy powering the long-lived UV emission, while deep radio limits exclude the presence of relativistic jets propagating into a low-density environment. We propose a model where the extreme luminosity and double-peaked temporal structure of ASASSN-15lh is powered by a central source of ionizing radiation that produces a sudden change in the ejecta opacity at later times. As a result, UV radiation can more easily escape, producing the second bump in the light curve. We discuss different interpretations for the intrinsic nature of the ionizing source. We conclude that, if the X-ray source is physically associated with the optical-UV transient, then ASASSN-15lh most likely represents the tidal disruption of a main-sequence star by the most massive spinning black hole detected to date. In this case, ASASSN-15lh and similar events discovered in the future would constitute the most direct probes of very massive, dormant, spinning, supermassive black holes in galaxies. Future monitoring of the X-rays may allow us to distinguish between the supernova hypothesis and the hypothesis of a tidal disruption event.

  6. X-Rays from the Location of the Double-humped Transient ASASSN-15lh

    PubMed Central

    Margutti, R.; Metzger, B. D.; Chornock, R.; Milisavljevic, D.; Berger, E.; Blanchard, P. K.; Guidorzi, C.; Migliori, G.; Kamble, A.; Lunnan, R.; Nicholl, M.; Coppejans, D. L.; Dall’Osso, S.; Drout, M. R.; Perna, R.; Sbarufatti, B.

    2017-01-01

    We present the detection of persistent soft X-ray radiation with Lx ~ 1041–1042 erg s−1 at the location of the extremely luminous, double-humped transient ASASSN-15lh as revealed by Chandra and Swift. We interpret this finding in the context of observations from our multiwavelength campaign, which revealed the presence of weak narrow nebular emission features from the host-galaxy nucleus and clear differences with respect to superluminous supernova optical spectra. Significant UV flux variability on short timescales detected at the time of the rebrightening disfavors the shock interaction scenario as the source of energy powering the long-lived UV emission, while deep radio limits exclude the presence of relativistic jets propagating into a low-density environment. We propose a model where the extreme luminosity and double-peaked temporal structure of ASASSN-15lh is powered by a central source of ionizing radiation that produces a sudden change in the ejecta opacity at later times. As a result, UV radiation can more easily escape, producing the second bump in the light curve. We discuss different interpretations for the intrinsic nature of the ionizing source. We conclude that, if the X-ray source is physically associated with the optical–UV transient, then ASASSN-15lh most likely represents the tidal disruption of a main-sequence star by the most massive spinning black hole detected to date. In this case, ASASSN-15lh and similar events discovered in the future would constitute the most direct probes of very massive, dormant, spinning, supermassive black holes in galaxies. Future monitoring of the X-rays may allow us to distinguish between the supernova hypothesis and the hypothesis of a tidal disruption event. PMID:28966348

  7. Evaluation of ovarian function and metabolic factors in women affected by polycystic ovary syndrome after treatment with D-Chiro-Inositol.

    PubMed

    Laganà, Antonio Simone; Barbaro, Luisa; Pizzo, Alfonsa

    2015-05-01

    To evaluate the effects of D-Chiro-Inositol in women affected by polycystic ovary syndrome (PCOS). We enrolled 48 patients, with homogeneous bio-physical characteristics, affected by PCOS and menstrual irregularities. These patients underwent treatment with 1 gr of D-Chiro-Inositol/die plus 400 mcg of Folic Acid/die orally for 6 months. We analyzed pre-treatment and post-treatment BMI, Systolic and Diastolic blood pressure, Ferriman-Gallwey score, Cremoncini score, serum LH, LH/FSH ratio, total and free testosterone, DHEA-S, Δ-4-androstenedione, SHBG, prolactin, glucose/IRI ratio, HOMA index, and resumption of regular menstrual cycles. We evidenced a statistically significant reduction of systolic blood pressure, Ferriman-Gallwey score, LH, LH/FSH ratio, total Testosterone, free Testosterone, ∆-4-Androstenedione, Prolactin, and HOMA Index; in the same patients, we noticed a statistically significant increase of SHBG and Glycemia/IRI ratio. Moreover, we observed statistically significant (62.5%; p < 0.05) post-treatment menstrual cycle regularization. D-Chiro-Inositol is effective in improving ovarian function and metabolism of patients affected by PCOS.

  8. ASASSN-15lh: A highly super-luminous supernova

    NASA Astrophysics Data System (ADS)

    Dong, Subo; Shappee, B. J.; Prieto, J. L.; Jha, S. W.; Stanek, K. Z.; Holoien, T. W.-S.; Kochanek, C. S.; Thompson, T. A.; Morrell, N.; Thompson, I. B.; Basu, U.; Beacom, J. F.; Bersier, D.; Brimacombe, J.; Brown, J. S.; Bufano, F.; Chen, Ping; Conseil, E.; Danilet, A. B.; Falco, E.; Grupe, D.; Kiyota, S.; Masi, G.; Nicholls, B.; Olivares E., F.; Pignata, G.; Pojmanski, G.; Simonian, G. V.; Szczygiel, D. M.; Woźniak, P. R.

    2016-01-01

    We report the discovery of ASASSN-15lh (SN 2015L), which we interpret as the most luminous supernova yet found. At redshift z = 0.2326, ASASSN-15lh reached an absolute magnitude of Mu,AB = -23.5 ± 0.1 and bolometric luminosity Lbol = (2.2 ± 0.2) × 1045 ergs s-1, which is more than twice as luminous as any previously known supernova. It has several major features characteristic of the hydrogen-poor super-luminous supernovae (SLSNe-I), whose energy sources and progenitors are currently poorly understood. In contrast to most previously known SLSNe-I that reside in star-forming dwarf galaxies, ASASSN-15lh appears to be hosted by a luminous galaxy (MK ≈ -25.5) with little star formation. In the 4 months since first detection, ASASSN-15lh radiated (1.1 ± 0.2) × 1052 ergs, challenging the magnetar model for its engine.

  9. Effects of melatonin implants in pony mares. 1. Acute effects.

    PubMed

    Peltier, M R; Robinson, G; Sharp, D C

    1998-04-15

    The effects of melatonin implant treatment over a four week period on LH, estradiol (E2) and progesterone (P4) secretion during the breeding season were studied in ovary-intact and ovariectomized pony mares. Mares with melatonin implants had significantly higher daytime melatonin concentrations than mares with sharm implants (P = 0.0065). In ovariectomized mares, LH secretion did not differ between mares with melatonin and sham implants. In ovary-intact mares, melatonin implants altered the pattern of LH secretion (P = 0.0023) in such a way that an increase in LH secretion was observed during the periovulatory period. Estradiol and P4 secretion were unaffected by melatonin implants. These results suggest that constant administration of melatonin may enhance the secretion of LH during the periovulatory surge but does not adversely affect E2, P4 or basal LH secretion in mares during the breeding season.

  10. Meta-analysis of randomized controlled trials comparing outcomes for stapled hemorrhoidopexy versus LigaSure hemorrhoidectomy for symptomatic hemorrhoids in adults.

    PubMed

    Lee, Ko-Chao; Chen, Hong-Hwa; Chung, Kuan-Chih; Hu, Wan-Hsiang; Chang, Chia-Lo; Lin, Shung-Eing; Tsai, Kai-Lung; Lu, Chien-Chang

    2013-01-01

    This purpose of the meta-analysis was to compare treatment outcomes for adult patients with symptomatic hemorrhoids treated by stapled hemorrhoidopexy or LigaSure hemorrhoidectomy. A search of public medical databases was made to identify randomized controlled trials (RCTs) comparing stapled hemorrhoidopexy (SH) with LigaSure hemorrhoidectomy (LH) for the treatment of adult patients with symptomatic grade 3 and grade 4 hemorrhoids. Postoperative pain as measured using a visual analog scale was the primary outcome, and rate of recurrent prolapse and postoperative bleeding were secondary outcome measures. Four RCTs were identified that met the inclusion criteria. Data for the pooled outcomes were analyzed using odds ratio (OR) analysis. None of the studies in the analysis indicated a significant difference between SH and LH for the outcomes VAS pain score, recurrence rate, or postoperative bleeding. Pooled analysis revealed a significant OR in favor of the SH method for recurrent prolapse (OR = 5.529, P = 0.016) for up to 2 years after surgery. No significant differences between the two methods were identified for VAS pain scores (OR = -1.060, P = 0.149) or postoperative bleeding OR = 1.188, P = 0.871). Pooled analysis of RCT results comparing SH to LH for symptomatic hemorrhoids revealed a significantly greater incidence of recurrent prolapse for SH. The two techniques were associated with similar levels of postoperative pain and postoperative bleeding. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  11. A Connective Tissue Disorder Caused by Mutations of the Lysyl Hydroxylase 3 Gene

    PubMed Central

    Salo, Antti M.; Cox, Helen; Farndon, Peter; Moss, Celia; Grindulis, Helen; Risteli, Maija; Robins, Simon P.; Myllylä, Raili

    2008-01-01

    Lysyl hydroxylase 3 (LH3, encoded by PLOD3) is a multifunctional enzyme capable of catalyzing hydroxylation of lysyl residues and O-glycosylation of hydroxylysyl residues producing either monosaccharide (Gal) or disaccharide (Glc-Gal) derivatives, reactions that form part of the many posttranslational modifications required during collagen biosynthesis. Animal studies have confirmed the importance of LH3, particularly in biosynthesis of the highly glycosylated type IV and VI collagens, but to date, the functional significance in vivo of this enzyme in man is predominantly unknown. We report here a human disorder of LH3 presenting as a compound heterozygote with recessive inheritance. One mutation dramatically reduced the sugar-transfer activity of LH3, whereas another abrogated lysyl hydroxylase activity; these changes were accompanied by reduced LH3 protein levels in cells. The disorder has a unique phenotype causing severe morbidity as a result of features that overlap with a number of known collagen disorders. PMID:18834968

  12. Solar Thermal Upper Stage Liquid Hydrogen Pressure Control Testing

    NASA Technical Reports Server (NTRS)

    Moore, J. D.; Otto, J. M.; Cody, J. C.; Hastings, L. J.; Bryant, C. B.; Gautney, T. T.

    2015-01-01

    High-energy cryogenic propellant is an essential element in future space exploration programs. Therefore, NASA and its industrial partners are committed to an advanced development/technology program that will broaden the experience base for the entire cryogenic fluid management community. Furthermore, the high cost of microgravity experiments has motivated NASA to establish government/aerospace industry teams to aggressively explore combinations of ground testing and analytical modeling to the greatest extent possible, thereby benefitting both industry and government entities. One such team consisting of ManTech SRS, Inc., Edwards Air Force Base, and Marshall Space Flight Center (MSFC) was formed to pursue a technology project designed to demonstrate technology readiness for an SRS liquid hydrogen (LH2) in-space propellant management concept. The subject testing was cooperatively performed June 21-30, 2000, through a partially reimbursable Space Act Agreement between SRS, MSFC, and the Air Force Research Laboratory. The joint statement of work used to guide the technical activity is presented in appendix A. The key elements of the SRS concept consisted of an LH2 storage and supply system that used all of the vented H2 for solar engine thrusting, accommodated pressure control without a thermodynamic vent system (TVS), and minimized or eliminated the need for a capillary liquid acquisition device (LAD). The strategy was to balance the LH2 storage tank pressure control requirements with the engine thrusting requirements to selectively provide either liquid or vapor H2 at a controlled rate to a solar thermal engine in the low-gravity environment of space operations. The overall test objective was to verify that the proposed concept could enable simultaneous control of LH2 tank pressure and feed system flow to the thruster without necessitating a TVS and a capillary LAD. The primary program objectives were designed to demonstrate technology readiness of the SRS concept at a system level as a first step toward actual flight vehicle demonstrations. More specific objectives included testing the pressure and feed control system concept hardware for functionality, operability, and performance. Valuable LH2 thermodynamic and fluid dynamics data were obtained for application to both the SRS concept and to future missions requiring space-based cryogen propellant management.

  13. Preliminary base heating environments for a generalized ALS LO2/LH2 launch vehicle, appendix 1 and 2

    NASA Technical Reports Server (NTRS)

    Bender, Robert L.; Reardon, John E.

    1989-01-01

    A secondary objective of contract NAS8-39141 is to provide base heating assessments, as required, to support Advanced Launch System (ALS) preliminary launch vehicle and propulsion system design studies. The ALS propulsion systems integration working group meeting (No. 3) recently completed in San Diego, California, focused attention on the need for base heating environment determination to provide preliminary requirements for LO2/LH2 propulsion systems currently being considered for ALS. We were requested to provide these environments for a range of possible propellant mixture and nozzle area ratios. Base heating environments can only be determined as a function of altitude when the engine operating conditions and vehicle base region geometry (engine arrangement) are known. If time dependent environments are needed to assess thermal loads, a trajectory must also be provided. These parameters are not fixed at this time since the ALS configurations and propulsion operating conditions are varied and continue to be studied by Phase B contractors. Therefore, for this study, a generalized LO2/LH2 system was selected along with a vehicle configuration consisting of a seven-engine booster and a three-engine core. MSFC provided guidance for the selection. We also selected a limited number of body points on the booster and core vehicles and engines for the environment estimates. Environments at these locations are representative of maximum heating conditions in the base region and are provided as a function of altitude only. Guidelines and assumptions for this assessment, methodology for determining the environments, and preliminary results are provided in this technical note. Refinements in the environments will be provided as the ALS design matures.

  14. Targeting the BH3-interacting domain death agonist to develop mechanistically unique antidepressants

    PubMed Central

    Malkesman, O; Austin, DR; Tragon, T; Henter, ID; Reed, JC; Pellecchia, M; Chen, G; Manji, HK

    2011-01-01

    The BH3-interacting domain death agonist (Bid) is a pro-apoptotic member of the B-cell lymphoma-2 (Bcl-2) protein family. Previous studies have shown that stress reduces levels of Bcl-2 in brain regions implicated in the pathophysiology of mood disorders, whereas antidepressants and mood stabilizers increase Bcl-2 levels. The Bcl-2 protein family has an essential role in cellular resilience as well as synaptic and neuronal plasticity and may influence mood and affective behaviors. This study inhibited Bid in mice using two pharmacological antagonists (BI-11A7 and BI-2A7); the selective serotonin reuptake inhibitor citalopram was used as a positive control. These agents were studied in several well-known rodent models of depression—the forced swim test (FST), the tail suspension test (TST), and the learned helplessness (LH) paradigm—as well as in the female urine sniffing test (FUST), a measure of sex-related reward-seeking behavior. Citalopram and BI-11A7 both significantly reduced immobility time in the FST and TST and attenuated escape latencies in mice that underwent the LH paradigm. In the FUST, both agents significantly improved duration of female urine sniffing in mice that had developed helplessness. LH induction increased the activation of apoptosis-inducing factor (AIF), a caspase-independent cell death constituent activated by Bid, and mitochondrial AIF expression was attenuated by chronic BI-11A7 infusion. Taken together, the results suggest that functional perturbation of apoptotic proteins such as Bid and, alternatively, enhancement of Bcl-2 function, is a putative strategy for developing novel therapeutics for mood disorders. PMID:21727899

  15. A Novel Population of Wake-Promoting GABAergic Neurons in the Ventral Lateral Hypothalamus.

    PubMed

    Venner, Anne; Anaclet, Christelle; Broadhurst, Rebecca Y; Saper, Clifford B; Fuller, Patrick M

    2016-08-22

    The largest synaptic input to the sleep-promoting ventrolateral preoptic area (VLPO) [1] arises from the lateral hypothalamus [2], a brain area associated with arousal [3-5]. However, the neurochemical identity of the majority of these VLPO-projecting neurons within the lateral hypothalamus (LH), as well as their function in the arousal network, remains unknown. Herein we describe a population of VLPO-projecting neurons in the LH that express the vesicular GABA transporter (VGAT; a marker for GABA-releasing neurons). In addition to the VLPO, these neurons also project to several other established sleep and arousal nodes, including the tuberomammillary nucleus, ventral periaqueductal gray, and locus coeruleus. Selective and acute chemogenetic activation of LH VGAT(+) neurons was profoundly wake promoting, whereas acute inhibition increased sleep. Because of its direct and massive inputs to the VLPO, this population may play a particularly important role in sleep-wake switching. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Pigment organization in the photosynthetic apparatus of Roseiflexus castenholzii.

    PubMed

    Collins, Aaron M; Xin, Yueyong; Blankenship, Robert E

    2009-08-01

    The light-harvesting-reaction center (LHRC) complex from the chlorosome-lacking filamentous anoxygenic phototroph (FAP), Roseiflexus castenholzii (R. castenholzii) was purified and characterized for overall pigment organization. The LHRC is a single complex that is comprised of light harvesting (LH) and reaction center (RC) polypeptides as well as an attached c-type cytochrome. The dominant carotenoid found in the LHRC is keto-gamma-carotene, which transfers excitation to the long wavelength antenna band with 35% efficiency. Linear dichroism and fluorescence polarization measurements indicate that the long wavelength antenna pigments absorbing around 880 nm are perpendicular to the membrane plane, with the corresponding Q(y) transition dipoles in the plane of the membrane. The antenna pigments absorbing around 800 nm, as well as the bound carotenoid, are oriented at a large angle with respect to the membrane. The antenna pigments spectroscopically resemble the well-studied LH2 complex from purple bacteria, however the close association with the RC makes the light harvesting component of this complex functionally more like LH1.

  17. Serum bioactive and immunoreactive luteinizing hormone and follicle-stimulating hormone levels in women with cycle abnormalities, with or without polycystic ovarian disease.

    PubMed

    Fauser, B C; Pache, T D; Lamberts, S W; Hop, W C; de Jong, F H; Dahl, K D

    1991-10-01

    Serum steroid, gonadotropin, and alpha-subunit levels were assessed in 35 women with cycle abnormalities [11 with and 24 without polycystic ovarian disease (PCOD) according to strict clinical and biochemical criteria] and 8 regularly cycling women in the early (cycle day 3 or 4) and mid (cycle day 7 or 8) follicular phase. LH and FSH levels were estimated using two immunological techniques [RIA and immunoradiometric assay (IRMA)] and in vitro bioassays (BIO), using mouse Leydig cells and rat granulosa cells, respectively. In PCOD patients mean alpha-subunit, free androgen index [FAI; testosterone x 100/sex hormone-binding globulin (SHBG)], androstenedione, estrone, and estradiol (E2) were significantly elevated compared to levels in the early follicular phase of control cycles and non-PCOD patients. In addition, in PCOD patients mean IRMA-LH and RIA-LH levels were distinctly increased (2.8- to 3.6 fold, respectively; both comparisons, P less than 0.001) compared to control values, but in the same order of magnitude (1.3- to 1.4-fold increments) as that in non-PCOD patients. However, the median BIO-LH level in PCOD patients was 5.9-fold higher than that in non-PCOD patients and 4.0-fold higher than the BIO-LH in the early follicular phase of control women. Consequently, the median BIO/IRMA-LH ratio was 4.8-fold higher in PCOD patients compared to non-PCOD patients. In women with cycle abnormalities, individual BIO/IRMA-LH ratios correlated with BIO-LH (rs = 0.48), FAI (rs = 0.39), free estrogens (E2/SHBG ratios; rs = 0 0.47), and dehydroepiandrosterone sulfate (rs = 0.60) concentrations. Mean IRMA-, RIA-, and BIO-FSH levels and BIO/IRMA-FSH ratios were not significantly different when various groups were compared. Although RIA- and IRMA-LH levels showed good correlation (rs = 0.88), RIA-LH levels were consistently higher, resulting in distinctly higher RIA-LH/FSH ratios (mean, 4.5) compared to IRMA-LH/FSH ratios (median, 1.8) in PCOD patients.(ABSTRACT TRUNCATED AT 400 WORDS)

  18. Determination of the topological shape of integral membrane protein light-harvesting complex LH2 from photosynthetic bacteria in the detergent solution by small-angle X-ray scattering.

    PubMed

    Hong, Xinguo; Weng, Yu-Xiang; Li, Ming

    2004-02-01

    The topological shape of the integral membrane protein light-harvesting complex LH2 from photosynthetic bacteria Rhodobacter spheroides 2.4.1 in detergent solution has been determined from synchrotron small-angle X-ray scattering data using direct curve-fitting by the ellipsoid, ab initio shape determination methods of simulated annealing algorithm and multipole expansion, respectively. The results indicate that the LH2 protein in aqueous solution is encapsulated by a monolayered detergent shell. The detergent-stabilized structure has the shape of an oblate plate, with a thickness of 40 A, a long axis of 110 A, and a short axis of 85 A. After correction for the detergent shell, the shape of the LH2 core is also an oblate plate with a height of 40 A, a long axis of 80 A, and a short axis of 55 A. In contrast to the cylindrical crystal structure with a height of 40 A and a diameter of 68 A, the molecular shape of the LH2 complex in detergent solution clearly deviates from the ringlike crystal structure, with an eccentricity found to be 0.59-consistent with the result of single molecular spectroscopy study of the isolated single LH2 molecules.

  19. Determination of the Topological Shape of Integral Membrane Protein Light-Harvesting Complex LH2 from Photosynthetic Bacteria in the Detergent Solution by Small-Angle X-Ray Scattering

    PubMed Central

    Hong, Xinguo; Weng, Yu-Xiang; Li, Ming

    2004-01-01

    The topological shape of the integral membrane protein light-harvesting complex LH2 from photosynthetic bacteria Rhodobacter spheroides 2.4.1 in detergent solution has been determined from synchrotron small-angle X-ray scattering data using direct curve-fitting by the ellipsoid, ab initio shape determination methods of simulated annealing algorithm and multipole expansion, respectively. The results indicate that the LH2 protein in aqueous solution is encapsulated by a monolayered detergent shell. The detergent-stabilized structure has the shape of an oblate plate, with a thickness of 40 Å, a long axis of 110 Å, and a short axis of 85 Å . After correction for the detergent shell, the shape of the LH2 core is also an oblate plate with a height of 40 Å, a long axis of 80 Å, and a short axis of 55 Å. In contrast to the cylindrical crystal structure with a height of 40 Å and a diameter of 68 Å, the molecular shape of the LH2 complex in detergent solution clearly deviates from the ringlike crystal structure, with an eccentricity found to be 0.59—consistent with the result of single molecular spectroscopy study of the isolated single LH2 molecules. PMID:14747343

  20. Direct hypothalamic and indirect trans-pallidal, trans-thalamic, or trans-septal control of accumbens signaling and their roles in food intake

    PubMed Central

    Urstadt, Kevin R.; Stanley, B. Glenn

    2015-01-01

    Due in part to the increasing incidence of obesity in developed nations, recent research aims to elucidate neural circuits that motivate humans to overeat. Earlier research has described how the nucleus accumbens shell (AcbSh) motivates organisms to feed by activating neuronal populations in the lateral hypothalamus (LH). However, more recent research suggests that the LH may in turn communicate with the AcbSh, both directly and indirectly, to re-tune the motivation to consume foods with homeostatic and food-related sensory signals. Here, we discuss the functional and anatomical evidence for an LH to AcbSh connection and its role in eating behaviors. The LH appears to modulate Acb activity directly, using neurotransmitters such as hypocretin/orexin or melanin concentrating hormone (MCH). The LH also indirectly regulates AcbSh activity through certain subcortical “relay” regions, such as the lateral septum (LS), ventral pallidum (VP), and paraventricular thalamus, using a variety of neurotransmitters. This review aims to summarize studies on these topics and outline a model by which LH circuits processing energy balance can modulate AcbSh neural activity to regulate feeding behavior. PMID:25741246

  1. Cycle O(CY1991) NLS trade studies and analyses report. Book 2, part 2: Propulsion

    NASA Technical Reports Server (NTRS)

    Cronin, R.; Werner, M.; Bonson, S.; Spring, R.; Houston, R.

    1992-01-01

    This report documents the propulsion system tasks performed in support of the National Launch System (NLS) Cycle O preliminary design activities. The report includes trades and analyses covering the following subjects: (1) Maximum Tank Stretch Study; (2) No LOX Bleed Performance Analysis; (3) LOX Bleed Trade Study; (4) LO2 Tank Pressure Limits; (5) LOX Tank Pressurization System Using Helium; (6) Space Transportation Main Engine (STME) Heat Exchanger Performance; (7) LH2 Passive Recirculation Performance Analysis; (8) LH2 Bleed/Recirculation Study; (9) LH2 Tank Pressure Limits; and (10) LH2 Pressurization System. For each trade study an executive summary and a detailed trade study are provided. For the convenience of the reader, a separate section containing a compilation of only the executive summaries is also provided.

  2. Radiometric errors in complex Fourier transform spectrometry.

    PubMed

    Sromovsky, Lawrence A

    2003-04-01

    A complex spectrum arises from the Fourier transform of an asymmetric interferogram. A rigorous derivation shows that the rms noise in the real part of that spectrum is indeed given by the commonly used relation sigmaR = 2X x NEP/(etaAomega square root(tauN)), where NEP is the delay-independent and uncorrelated detector noise-equivalent power per unit bandwidth, +/- X is the delay range measured with N samples averaging for a time tau per sample, eta is the system optical efficiency, and Aomega is the system throughput. A real spectrum produced by complex calibration with two complex reference spectra [Appl. Opt. 27, 3210 (1988)] has a variance sigmaL2 = sigmaR2 + sigma(c)2 (Lh - Ls)2/(Lh - Lc)2 + sigma(h)2 (Ls - Lc)2/(Lh - Lc)2, valid for sigmaR, sigma(c), and sigma(h) small compared with Lh - Lc, where Ls, Lh, and Lc are scene, hot reference, and cold reference spectra, respectively, and sigma(c) and sigma(h) are the respective combined uncertainties in knowledge and measurement of the hot and cold reference spectra.

  3. Cryogenic foam insulation for LH2 fueled subsonic transports

    NASA Technical Reports Server (NTRS)

    Sharpe, E. L.; Helenbrook, R. G.

    1978-01-01

    Shortages of petroleum-based aircraft fuels are foreseen before the end of the century. To cope with such shortages, NASA is developing a commercial aircraft which can operate on liquid hydrogen. Various foam insulators for LH2 storage are considered in terms of thermal performance and service life. Of the cryogenic foams considered (plain foam, foam with flame retardants and fiberglass reinforcement, and foam with vapor barriers), polyurethane foams were found to be the best. Tests consisted of heating a 5 cm layer of insulation around an aluminum tank containing LH2 to 316 K, and then cooling it to 266 K, while the inner surface was maintained at LH2 temperature (20 K).

  4. Removal of Escherichia coli and Faecal Coliforms from Surface Water and Groundwater by Household Water Treatment Devices/Systems: A Sustainable Solution for Improving Water Quality in Rural Communities of the Southern African Development Community Region

    PubMed Central

    Mwabi, Jocelyne K.; Mamba, Bhekie B.; Momba, Maggy N. B.

    2012-01-01

    There is significant evidence that household water treatment devices/systems (HWTS) are capable of dramatically improving microbially contaminated water quality. The purpose of this study was to examine five filters [(biosand filter-standard (BSF-S); biosand filter-zeolite (BSF-Z); bucket filter (BF); ceramic candle filter (CCF); and silver-impregnated porous pot (SIPP)] and evaluate their ability to improve the quality of drinking water at the household level. These HWTS were manufactured in the workshop of the Tshwane University of Technology and evaluated for efficiency to remove turbidity, faecal coliforms and Escherichia coli from multiple water source samples, using standard methods. The flow rates ranged from 0.05 L/h to 2.49 L/h for SIPP, 1 L/h to 4 L/h for CCF, 0.81 L/h to 6.84 L/h for BSF-S, 1.74 L/h to 19.2 L/h and 106.5 L/h to 160.5 L/h for BF The turbidity of the raw water samples ranged between 2.17 and 40.4 NTU. The average turbidity obtained after filtration ranged from 0.6 to 8 NTU (BSF-S), 1 to 4 NTU (BSF-Z), 2 to 11 NTU (BF), and from 0.6 to 7 NTU (CCF) and 0.7 to 1 NTU for SIPP. The BSF-S, BSF-Z and CCF removed 2 to 4 log10 (99% to 100%) of coliform bacteria, while the BF removed 1 to 3 log (90% to 99.9%) of these bacteria. The performance of the SIPP in removing turbidity and indicator bacteria (>5 log10, 100%) was significantly higher compared to that of the other HWTS (p < 0.05). The findings of this study indicate that the SIPP can be an effective and sustainable HWTS for the Southern African Development Community (SADC) rural communities, as it removed the total concentration of bacteria from test water, can be manufactured using locally available materials, and is easy to operate and to maintain. PMID:22470284

  5. Performance Gains of Propellant Management Devices for Liquid Hydrogen Depots

    NASA Technical Reports Server (NTRS)

    Hartwig, Jason W.; McQuillen, John B.; Chato, David J.

    2013-01-01

    This paper presents background, experimental design, and preliminary experimental results for the liquid hydrogen bubble point tests conducted at the Cryogenic Components Cell 7 facility at the NASA Glenn Research Center in Cleveland, Ohio. The purpose of the test series was to investigate the parameters that affect liquid acquisition device (LAD) performance in a liquid hydrogen (LH2) propellant tank, to mitigate risk in the final design of the LAD for the Cryogenic Propellant Storage and Transfer Technology Demonstration Mission, and to provide insight into optimal LAD operation for future LH2 depots. Preliminary test results show an increase in performance and screen retention over the low reference LH2 bubble point value for a 325 2300 screen in three separate ways, thus improving fundamental LH2 LAD performance. By using a finer mesh screen, operating at a colder liquid temperature, and pressurizing with a noncondensible pressurant gas, a significant increase in margin is achieved in bubble point pressure for LH2 screen channel LADs.

  6. Liquid Propellant Blast Yields for Delta IV Heavy Vehicles

    DTIC Science & Technology

    2010-07-01

    explode simultaneously, up to 1.4 million lb of liquid oxygen and liquid hydrogen (LO2/ LH2 ) may be involved and at least partially contribute to the...in the third so as to prevent them from contributing to the blast yield. Since the PYRO LO2/ LH2 yield model was originally developed using data from...that mixing interfaces between the LO2 and LH2 tanks for all three CBCs occur simultaneously, then a reasonable argument can be made for all three

  7. Liquid hydrogen production and commercial demand in the United States

    NASA Technical Reports Server (NTRS)

    Heydorn, Barbara

    1990-01-01

    Kennedy Space Center, the single largest purchaser of liquid hydrogen (LH2) in the United States, evaluated current and anticipated hydrogen production and consumption in the government and commercial sectors. Specific objectives of the study are as follows: (1) identify LH2 producers in the United States and Canada during 1980-1989 period; (2) compile information in expected changes in LH2 production capabilities over the 1990-2000 period; (3) describe how hydrogen is used in each consuming industry and estimate U.S. LH2 consumption for the chemicals, metals, electronics, fats and oil, and glass industries, and report data on a regional basis; (4) estimate historical and future consumption; and (5) assess the influence of international demands on U.S. plants.

  8. Urinary excretion of LH and testosterone from male rats during exposure to increased gravity: post-spaceflight and centrifugation

    NASA Technical Reports Server (NTRS)

    Ortiz, R. M.; Wade, C. E.; Morey-Holton, E.

    2000-01-01

    A dissociation between plasma luteinizing hormone (LH) and testosterone (T) appears to exist during exposure to altered gravity. The pulsatile nature of LH release and the diurnal variability of T secretion may mask or bias the effects of altered gravity on the pituitary-gonadal axis when analyzing plasma concentrations. Therefore, we examined the relationship between the excretion of urinary LH and T in male Sprague-Dawley rats during exposure to increased gravity upon return to Earth following a 14-day spaceflight (n = 6) and by 12 days of centrifugation at 2g (n = 8). Excreted LH and T were elevated on the first 3 days postflight. Excreted T was elevated between Days 1 and 8 of centrifugation; however, excreted LH was reduced on Days 2 and 3 compared with control animals. Excreted LH and T were significantly correlated (R = 0.731 and 0.706, respectively) in postspaceflight and centrifuged animals. Correlation curves had similar slopes (0.0213 and 0.023, respectively), but different y-intercepts (-1.43 and 3.32, respectively). The sustained increase in excreted T during centrifugation suggests that the pituitary-gonadal axis in postspaceflight animals may adapt quicker to increased gravity. The upward shift in the correlation curve exhibited by the centrifuged animals suggests that the sensitivity of LH-induced T release is increased in these animals. The previous dissociation between plasma LH and T during altered gravity was not observed in the present study in which excreted LH and T were measured.

  9. Assessment of ovarian reserve in euthyroid adolescents with Hashimoto thyroiditis.

    PubMed

    Pirgon, Ozgur; Sivrice, Cigdem; Demirtas, Hakan; Dundar, Bumin

    2016-01-01

    We aimed to investigate the ovarian function and reserve in euthyroid adolescents (TSH < 2.5 mIU/L) diagnosed with Hashimoto thyroiditis (HT). This case-control study included 30 adolescent girls (mean age 15.1 ± 1.4 years) newly diagnosed as HT with presence of high thyroid antibodies with gland heterogeneity in ultrasound and age-matched 30 healthy female subjects. Anti-ovarian antibody (AOAb), LH/FSH ratio, estradiol, anti-mullerian hormone (AMH), inhibin-B, total testosterone, antral follicle count, ovarian volumes and uterine length were measured. The clinical, laboratory, and ultrasound data of the HT and control groups were compared. There were no significant differences between the girls with HT and healthy controls in relation to LH/FSH ratio, estradiol and inhibin-B levels. AOAb (p = 0.02), AMH (p = 0.007) and total testosterone levels were higher in HT group than the control group (p = 0.03). AOAb level was found to be positively correlated with LH/FSH ratio (p = 0.03), AMH (p = 0.01) and inhibin-B (p < 0.001) in HT group. This study demonstrated that the adolescent girls diagnosed with autoimmune thyroiditis had normal ovarian reserve based on measurements of AMH, inhibin B, FSH, LH/FSH ratio, estradiol and antral follicle counts.

  10. Errors in insulin treatment management and risk of lipohypertrophy.

    PubMed

    Pozzuoli, Giuseppe Maria; Laudato, Mario; Barone, Maria; Crisci, Franco; Pozzuoli, Bianca

    2018-01-01

    Lipohypertrophy (LH) represents the most common skin-related complication associated with insulin therapy. Our aim is to estimate the prevalence of LH among insulin-treated patients, to identify its association with errors in insulin injection technique and storage, and the correlation between LH, risk of hypoglycemia, and glycemic control. Consecutive patients with T1DM or T2DM, attending a diabetes clinic for a routine visit, were administered an anonymous questionnaire investigating the modalities of insulin injection, the correct use of pen device, insulin storage, and reported frequency of hypoglycemic episodes. The presence of LH was assessed by inspection and palpation of injection sites. Overall, 352 patients were enrolled (mean age 68 ± 12 years, 43.2% males, 88.9% with T2DM, mean duration of insulin therapy 9.1 ± 8.6 years). The prevalence of LH was 42.9%. At multivariate analysis, the strongest correlates of LH were not spacing injections (OR 20.4; 95% CI 10.5-39.6) and not rotating the site of injection (OR 2.01; 95% CI 1.08-3.75). Increasing doses of insulin and longer duration of insulin therapy also increased the risk of LH. The presence of LH was associated with a 2.7 times higher risk of severe hypoglycemia. Higher daily insulin doses, lack of rotation of injection sites, and keeping insulin in use in the refrigerator were independent correlates of higher HbA1c levels. Insulin injection technique is suboptimal in many patients, highlighting the need for improved patient education. Increasing the awareness of the importance of preventing lipohypertrophy and insulin injection errors represents an important tool to reduce the clinical, social, and economic burden of diabetes.

  11. Conceptual Design, Feasibility and Payoff Analysis of a Third Stage for EELV

    DTIC Science & Technology

    2014-06-01

    the overall vehicle architecture, identifying locations for modification or stage shape. Trade studies of various propellant types (LOX/ LH2 , LOX/RP...or stage shape. Trade studies of various propellant types (LOX/ LH2 , LOX/RP, LOX/methane, hydrazine monopropellant) were included in the analysis...Geostationary transfer orbit Isp = Specific impulse LEO = Low Earth Orbit LOX = Liquid oxygen LH2 = Liquid hydrogen POST = Program to

  12. Demonstrating the Importance of `` Good" Models of Land Surface Hydrological Processes

    NASA Astrophysics Data System (ADS)

    Pitman, A.; Irannejad, P.; McGuffie, K.; Henderson-Sellers, A.

    2003-12-01

    To reduce the uncertainty in the prediction of land surface climates,, the Atmospheric Model Intercomparison Project (AMIP) Diagnostic Subproject 12 (DSP 12) and the Project for Intercomparison of Land-surface Parameterisation Schemes (PILPS) have analysed dependence of climate simulations on the land-surface schemes (LSSs). This analysis has comprised three efforts: (i) proving that LSSs matter in coupled simulations; (ii) investigating whether improvements in LSSs have occurred over time; and (iii) searching for novel means of validating LSS predictions. In the first, Irannejad et al. (2003) introduce a novel method for evaluating the dependence of 19 AMIP AGCMs' LH on the LSS by excluding the impact of the atmosphere. Pseudo LSSs (PLSSs) for LH in the form of multi-variable linear models expressing mean monthly LH as a function of atmospheric forcing are developed. Analysis over three large and climatically diverse river basins shows estimates of mean annual LH from the PLSSs agreeing well with the AGCMs' simulations. RMS errors range from 0.4 to 2.2 W m-2 depending on the region and the AGCM. When the PLSSs are driven by single atmospheric forcings, different LSSs behave differently, and the variability of mean annual LH among AGCMs increases. The second strand of our investigation uncovered a clear generational sequence of land-surface schemes: first generation 'no canopy'; second generation ` SiBlings'; and ` recent schemes'. We conclude that although continental surface modelling has improved over the last 30 years, full confidence remains elusive, in part due to tuning to available observations. Finally, we show that stable water isotopes challenge predictions of evaporation and condensation processes. These three-pronged findings prove that LSSs are important to AGCM and coupled climate predictions; demonstrate that new, or changed, land-surface components increase diversity among simulations; underline the need for validation data and also challenge current parameterisations with novel observations.

  13. Correlation between LH secretion in castrated rats with cellular proliferation and synthesis of DNA in the anterior pituitary gland.

    PubMed

    Romano, M I; Machiavelli, G A; Pérez, R L; Carricarte, V; Burdman, J A

    1984-07-01

    The relationship between the release of LH and the synthesis of DNA was studied in the anterior pituitary gland of castrated rats. Cell types were characterized immunocytochemically. Castration significantly (P less than 0.01) increased the concentration of LH in serum (1326%) and the incorporation of [3H]thymidine into pituitary DNA (72%). This was accompanied by an increment in the activity of the enzyme DNA polymerase-alpha (58%) and in the number of mitoses (from 2 +/- 0.1/mm2 in intact rats to 21 +/- 0.8/mm2 15 days after castration). Only 20% of the mitoses found in the pituitary gland of castrated rats were positively stained with the antiserum against the beta-subunit of LH. The other 80% did not stain either with LH antiserum or with antisera against the other pituitary hormones. There was a significant (P less than 0.01) increase in the number of LH cells in castrated rats (48%). All the changes produced in the anterior pituitary gland after castration were prevented by the administration of dihydrotestosterone. The results demonstrate that a stimulation of LH release is followed by an increase of DNA synthesis and cell proliferation of gonadotrophs in the anterior pituitary gland.

  14. Exploring the pathophysiology of hypogonadism in men with type 2 diabetes: kisspeptin-10 stimulates serum testosterone and LH secretion in men with type 2 diabetes and mild biochemical hypogonadism.

    PubMed

    George, Jyothis T; Veldhuis, Johannes D; Tena-Sempere, Manuel; Millar, Robert P; Anderson, Richard A

    2013-07-01

    Low serum testosterone is commonly observed in men with type 2 diabetes (T2DM), but the neuroendocrine pathophysiology remains to be elucidated. The hypothalamic neuropeptide kisspeptin integrates metabolic signals with the reproductive axis in animal models. We hypothesized that administration of exogenous kisspeptin-10 will restore luteinizing hormone (LH) and testosterone secretion in hypotestosteronaemic men with T2DM. Five hypotestosteronaemic men with T2DM (age 33·6 ± 3 years, BMI 40·6 ± 6·3, total testosterone 8·5 ± 1·0 nmol/l, LH 4·7 ± 0·7 IU/l, HbA1c 7·4±2%, duration of diabetes <5 years) and seven age-matched healthy men. EXPERIMENT 1: Mean LH increased in response to intravenous administration of kisspeptin-10 (0·3 mcg/kg bolus) both in healthy men (5·5 ± 0·8 to 13·9 ± 1·7 IU/l P < 0·001) and in men with T2DM (4·7 ± 0·7 to 10·7 ± 1·2 IU/l P = 0·02) with comparable ΔLH (P = 0·18). EXPERIMENT 2: Baseline 10-min serum sampling for LH and hourly testosterone measurements were performed in four T2DM men over 12 h. An intravenous infusion of kisspeptin-10 (4 mcg/kg/h) was administered for 11 h, 5 days later. There were increases in LH (3·9 ± 0·1 IU/l to 20·7 ± 1·1 IU/l P = 0·03) and testosterone (8·5 ± 1·0 to 11·4 ± 0·9 nmol/l, P = 0·002). LH pulse frequency increased from 0·6 ± 0·1 to 0·9 ± 0 pulses/h (P = 0·05) and pulsatile component of LH secretion from 32·1 ± 8·0 IU/l to 140·2 ± 23·0 IU/l (P = 0·007). Kisspeptin-10 administration increased LH pulse frequency and LH secretion in hypotestosteronaemic men with T2DM in this proof-of-concept study, with associated increases in serum testosterone. These data suggest a potential novel therapeutic role for kisspeptin agonists in enhancing endogenous testosterone secretion in men with T2DM and central hypogonadism. © 2012 John Wiley & Sons Ltd.

  15. Structure of a Reptilian Adenovirus Reveals a Phage Tailspike Fold Stabilizing a Vertebrate Virus Capsid.

    PubMed

    Menéndez-Conejero, Rosa; Nguyen, Thanh H; Singh, Abhimanyu K; Condezo, Gabriela N; Marschang, Rachel E; van Raaij, Mark J; San Martín, Carmen

    2017-10-03

    Although non-human adenoviruses (AdVs) might offer solutions to problems posed by human AdVs as therapeutic vectors, little is known about their basic biology. In particular, there are no structural studies on the complete virion of any AdV with a non-mammalian host. We combine mass spectrometry, cryo-electron microscopy, and protein crystallography to characterize the composition and structure of a snake AdV (SnAdV-1, Atadenovirus genus). SnAdV-1 particles contain the genus-specific proteins LH3, p32k, and LH2, a previously unrecognized structural component. Remarkably, the cementing protein LH3 has a trimeric β helix fold typical of bacteriophage host attachment proteins. The organization of minor coat proteins differs from that in human AdVs, correlating with higher thermostability in SnAdV-1. These findings add a new piece to the intriguing puzzle of virus evolution, hint at the use of cell entry pathways different from those in human AdVs, and will help development of new, thermostable SnAdV-1-based vectors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Harnessing Solar Power: Novel Strategies for Rational Design of Photocatalysts and Photovoltaic Materials

    DTIC Science & Technology

    2015-09-01

    Complex 2 ( LH2 ) of Rhodobacter sphaeroides with Two- Dimensional Spectroscopy” J. Chem. Phys. 139, 155101 2013. A.F. Fidler, V.P. Singh, P.D. Long...P.D. Dahlberg, and G.S. Engel, “Time Scales of Coherent Dynamics in the Light-Harvesting Complex 2 ( LH2 ) of Rhodobacter sphaeroides” J. Phys. Chem...Spectroscopy of the Light-harvesting Complex LH2 ” Opt. Lett. 36:9 1665-1667 2011 E. Harel, A.F. Fidler, and G.S. Engel, “Single-Shot GRadient

  17. Accelerated Episodic LH Release Accompanies Blunted Progesterone Regulation in PCOS-like Female Rhesus Monkeys (Macaca mulatta) Exposed to Testosterone During Early-to-Mid Gestation.

    PubMed

    Abbott, David H; Vepraskas, Sarah H; Horton, Teresa H; Terasawa, Ei; Levine, Jon E

    2018-06-15

    Ovarian theca cell hyperandrogenism in women with PCOS is compounded by androgen receptor-mediated impairment of estradiol and progesterone negative feedback regulation of episodic LH release. The resultant LH hypersecretion, likely the product of accelerated episodic release of GnRH from the median eminence of the hypothalamus, hyperstimulates ovarian theca cell steroidogenesis, enabling testosterone (T) and androstenedione excess. Prenatally androgenized female monkeys (PA) exposed to fetal male levels of T during early-to-mid gestation, when adult, demonstrate PCOS-like traits, including high T and LH levels. This study tests the hypothesis that progesterone resistance-associated acceleration in episodic LH release contributes to PA monkey LH excess. 4 PA and 3 regularly cycling, healthy control adult female rhesus monkeys of comparable age and body mass index underwent (1) a 10 h, frequent intravenous sampling assessment for LH episodic release, immediately followed by (2) IV infusion of exogenous GnRH to quantify continuing pituitary LH responsiveness, and subsequently (3) an SC injection of a progesterone receptor antagonist, mifepristone, to examine LH responses to blockade of progesterone-mediated action. Compared to controls, the relatively hyperandrogenic PA females exhibited ~100% increase (p = 0.037) in LH pulse frequency, positive correlation of LH pulse amplitude (p = 0.017) with androstenedione, ~100% greater increase (p = 0.034) in acute (0--10 min) LH responses to exogenous GnRH, and an absence (p = 0.008) of modest LH elevation following acute progesterone receptor blockade suggestive of diminished progesterone negative feedback. Such dysregulation of LH release in PCOS-like monkeys implicates impaired feedback control of episodic release of hypothalamic GnRH reminiscent of PCOS neuroendocrinopathy. 2018 S. Karger AG, Basel.

  18. Influence of hormonal control on LH pulsatility and secretion in women with classical congenital adrenal hyperplasia.

    PubMed

    Bachelot, Anne; Chakhtoura, Zeina; Plu-Bureau, Geneviève; Coudert, Mathieu; Coussieu, Christiane; Badachi, Yasmina; Dulon, Jérome; Charbit, Beny; Touraine, Philippe

    2012-10-01

    Women with classical congenital adrenal hyperplasia (CAH) exhibit reduced fertility due to several factors including anovulation. This has been attributed to a disturbed gonadotropic axis as in polycystic ovary syndrome (PCOS), but there is no precise evaluation. Our aim was to evaluate the gonadotropic axis and LH pulsatility patterns and to determine factor(s) that could account for the potential abnormality of LH pulsatility. Case/control study. Sixteen CAH women (11 with the salt-wasting form and five with the simple virilizing form), aged from 18 to 40 years, and 16 age-matched women, with regular menstrual cycles (28 ± 3 days), were included. LH pulse patterns over 6 h were determined in patients and controls. No differences were observed between patients and controls in terms of mean LH levels, LH pulse amplitude, or LH frequency. In CAH patients, LH pulsatility patterns were heterogeneous, leading us to perform a clustering analysis of LH data, resulting in a two-cluster partition. Patients in cluster 1 had similar LH pulsatility patterns to the controls. Patients in cluster 2 had: lower LH pulse amplitude and frequency and presented menstrual cycle disturbances more frequently; higher 17-OH progesterone, testosterone, progesterone, and androstenedione levels; and lower FSH levels. LH pulsatility may be normal in CAH women well controlled by hormonal treatment. Undertreatment is responsible for hypogonadotropic hypogonadism, with low LH pulse levels and frequency, but not PCOS. Suppression of progesterone and androgen concentrations during the follicular phase of the menstrual cycle should be a major objective in these patients.

  19. Evaluation of basal sex hormone levels for activation of the hypothalamic-pituitary-gonadal axis.

    PubMed

    Ding, Yu; Li, Juan; Yu, Yongguo; Yang, Peirong; Li, Huaiyuan; Shen, Yongnian; Huang, Xiaodong; Liu, Shijian

    2018-03-28

    This study aimed to identify the predictive value of basal sex hormone levels for activation of the hypothalamic-pituitary-gonadal (HPG) axis in girls. Gonadotropin-releasing hormone (GnRH) stimulation tests were performed and evaluated in a total of 1750 girls with development of secondary sex characteristics. Correlation analyses were conducted between basal sex hormones and peak luteinizing hormone (LH) levels ≥5 IU/L during the GnRH stimulation test. Receiver operating characteristic (ROC) curves for basal levels of LH, follicle-stimulating hormone (FSH), LH/FSH, and estradiol (E2) before the GnRH stimulation test were plotted. The area under the curve (AUC) and 95% confidence intervals (CIs) were measured for each curve. The maximum AUC value was observed for basal LH levels (0.77, 95% CI: 0.74-0.79), followed by basal FSH levels (0.73, 95% CI: 0.70-0.75), the basal LH/FSH ratio (0.68, 95% CI: 0.65-0.71), and basal E2 levels (0.61, 95% CI: 0.59-0.64). The appropriate cutoff value of basal LH levels associated with a positive response of the GnRH stimulation test was 0.35 IU/L, with a sensitivity of 63.96% and specificity of 76.3% from the ROC curves when Youden's index showed the maximum value. When 100% of patients had peak LH levels ≥5 IU/L, basal LH values were >2.72 IU/L, but the specificity was only 5.45%. Increased basal LH levels are a significant predictor of a positive response during the GnRH stimulation test for assessing activation of the HPG axis in most girls with early pubertal signs.

  20. Prostate Androgen-Regulated Mucin-Like protein 1: A Novel Regulator of Progesterone Metabolism

    PubMed Central

    Park, Ji Yeon; Jang, Hyein; Curry, Thomas E.; Sakamoto, Aiko

    2013-01-01

    The LH surge reprograms preovulatory follicular cells to become terminally differentiated luteal cells which produce high levels of progesterone and become resistant to apoptosis. PARM1 (prostate androgen regulated mucin-like protein 1) has been implicated in cell differentiation and cell survival in nonovarian cells, but little is known about PARM1 in the ovary. This study demonstrated that the LH surge induced a dramatic increase in Parm1 expression in periovulatory follicles and newly forming CL in both cycling and immature rat models. We further demonstrated that hCG increases Parm1 expression in granulosa cell cultures. The in vitro up-regulation of Parm1 expression was mediated by hCG-activated multiple signaling pathways and transcriptional activation of this gene. Parm1 knockdown increased the viability of cultured granulosa cells but resulted in a decrease in progesterone levels. The inhibitory effect of Parm1 silencing on progesterone was reversed by adenoviral mediated add-back expression of Parm1. Parm1 silencing had little effect on the expression of genes involved in progesterone biosynthesis and metabolism such as Scarb1, Ldlr, Vldlr, Scp2, Star, Cyp11a1, Hsd3b, and Srd5a1, while decreasing the expression of Akr1c3. Analyses of culture media steroid levels revealed that Parm1 knockdown had no effect on pregnenolone levels, while resulting in time-dependent decreases in progesterone and 20α-dihydroprogesterone and accelerated accumulation of 5α-pregnanediol. This study revealed that the up-regulation of Parm1 expression promotes progesterone and 20α-dihydroprogesterone accumulation in luteinizing granulosa cells by inhibiting progesterone catabolism to 5α-pregnanediol. PARM1 contributes to ovulation and/or luteal function by acting as a novel regulator of progesterone metabolism. PMID:24085821

  1. Role of Neurokinin B in the Control of Female Puberty and Its Modulation by Metabolic Status

    PubMed Central

    Navarro, Víctor M.; Ruiz-Pino, Francisco; Sánchez-Garrido, Miguel A.; García-Galiano, David; Hobbs, Samuel J.; Manfredi-Lozano, María; León, Silvia; Sangiao-Alvarellos, Susana; Castellano, Juan M.; Clifton, Donald K.; Pinilla, Leonor; Steiner, Robert A.; Tena-Sempere, Manuel

    2012-01-01

    Human genetic studies have revealed that neurokinin B (NKB) and its receptor, NK3R, are essential elements for normal reproduction; however, the precise role of NKB-NK3R signaling in the initiation of puberty remains un known. We investigated here the regulation of Tac2 and Tacr3 mRNAs (encoding NKB and NK3R, respectively) in female rats and demonstrated that their hypothalamic expression is increased along postnatal maturation. At puberty, both genes were widely expressed throughout the brain, including the lateral hypothalamic area (LHA) and the arcuate nucleus (ARC)/medial basal hypothalamus, where the expression of Tacr3 increased across pubertal transition. We showed that central administration of senktide (NK3R agonist), induced LH secretion in pre- and peri-pubertal females. Conversely, chronic infusion of an NK3R antagonist during puberty moderately delayed the timing of vaginal opening (VO) and tended to decrease LH levels. The expression of NKB and its receptor was sensitive to changes in metabolic status during puberty, as reflected by a reduction in Tacr3 (and to a lesser extent, Tac2) expression in the ARC after a 48-h fast. Yet, acute LH responses to senktide in pubertal females were preserved, if not augmented under fasting conditions, suggesting sensitization of the NKB-NK3R-GnRH signaling pathway under metabolic distress. Moreover, repeated administration of senktide to female rats with pubertal arrest due to chronic undernutrition rescued VO (in ~50% of animals) and potently elicited LH release. Altogether, our observations suggest that NKB-NK3R signaling plays a role in pubertal maturation and that its alterations may contribute to pubertal disorders linked to metabolic stress and negative energy balance. PMID:22396413

  2. Another look at category effects on colour perception and their left hemispheric lateralisation: no evidence from a colour identification task.

    PubMed

    Suegami, Takashi; Aminihajibashi, Samira; Laeng, Bruno

    2014-05-01

    The present study aimed to replicate category effects on colour perception and their lateralisation to the left cerebral hemisphere (LH). Previous evidence for lateralisation of colour category effects has been obtained with tasks where a differently coloured target was searched within a display and participants reported the lateral location of the target. However, a left/right spatial judgment may yield LH-laterality effects per se. Thus, we employed an identification task that does not require a spatial judgment and used the same colour set that previously revealed LH-lateralised category effects. The identification task was better performed with between-category colours than with within-category task both in terms of accuracy and latency, but such category effects were bilateral or RH-lateralised, and no evidence was found for LH-laterality effects. The accuracy scores, moreover, indicated that the category effects derived from low sensitivities for within-blue colours and did not reflect the effects of categorical structures on colour perception. Furthermore, the classic "category effects" were observed in participants' response biases, instead of sensitivities. The present results argue against both the LH-lateralised category effects on colour perception and the existence of colour category effects per se.

  3. Light-Harvesting Antenna System from the Phototrophic Bacterium Roseiflexus castenholzii

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Collins, Aaron M.; Qian, Pu; Tang, Qun

    Photosynthetic organisms have evolved diverse light-harvesting complexes to harness light of various qualities and intensities. Photosynthetic bacteria can have (bacterio)chlorophyll Q y antenna absorption bands ranging from ~650 to ~1100 nm. This broad range of wavelengths has allowed many organisms to thrive in unique light environments. Roseiflexus castenholzii is a niche-adapted, filamentous anoxygenic phototroph (FAP) that lacks chlorosomes, the dominant antenna found in most green bacteria, and here we describe the purification of a full complement of photosynthetic complexes: the light-harvesting (LH) antenna, reaction center (RC), and core complex (RC-LH). By high-performance liquid chromatography separation of bacteriochlorophyll and bacteriopheophytin pigmentsmore » extracted from the core complex and the RC, the number of subunits that comprise the antenna was determined to be 15 ± 1. Resonance Raman spectroscopy of the carbonyl stretching region displayed modes indicating that 3C-acetyl groups of BChl a are all involved in molecular interactions probably similar to those found in LH1 complexes from purple photosynthetic bacteria. Finally, two-dimensional projections of negatively stained core complexes and the LH antenna revealed a closed, slightly elliptical LH ring with an average diameter of 130 ± 10 Å surrounding a single RC that lacks an H-subunit but is associated with a tetraheme c-type cytochrome.« less

  4. Gaussian Mixture Modeling of Hemispheric Lateralization for Language in a Large Sample of Healthy Individuals Balanced for Handedness

    PubMed Central

    Mazoyer, Bernard; Zago, Laure; Jobard, Gaël; Crivello, Fabrice; Joliot, Marc; Perchey, Guy; Mellet, Emmanuel; Petit, Laurent; Tzourio-Mazoyer, Nathalie

    2014-01-01

    Hemispheric lateralization for language production and its relationships with manual preference and manual preference strength were studied in a sample of 297 subjects, including 153 left-handers (LH). A hemispheric functional lateralization index (HFLI) for language was derived from fMRI acquired during a covert sentence generation task as compared with a covert word list recitation. The multimodal HFLI distribution was optimally modeled using a mixture of 3 and 4 Gaussian functions in right-handers (RH) and LH, respectively. Gaussian function parameters helped to define 3 types of language hemispheric lateralization, namely “Typical” (left hemisphere dominance with clear positive HFLI values, 88% of RH, 78% of LH), “Ambilateral” (no dominant hemisphere with HFLI values close to 0, 12% of RH, 15% of LH) and “Strongly-atypical” (right-hemisphere dominance with clear negative HFLI values, 7% of LH). Concordance between dominant hemispheres for hand and for language did not exceed chance level, and most of the association between handedness and language lateralization was explained by the fact that all Strongly-atypical individuals were left-handed. Similarly, most of the relationship between language lateralization and manual preference strength was explained by the fact that Strongly-atypical individuals exhibited a strong preference for their left hand. These results indicate that concordance of hemispheric dominance for hand and for language occurs barely above the chance level, except in a group of rare individuals (less than 1% in the general population) who exhibit strong right hemisphere dominance for both language and their preferred hand. They call for a revisit of models hypothesizing common determinants for handedness and for language dominance. PMID:24977417

  5. Gaussian mixture modeling of hemispheric lateralization for language in a large sample of healthy individuals balanced for handedness.

    PubMed

    Mazoyer, Bernard; Zago, Laure; Jobard, Gaël; Crivello, Fabrice; Joliot, Marc; Perchey, Guy; Mellet, Emmanuel; Petit, Laurent; Tzourio-Mazoyer, Nathalie

    2014-01-01

    Hemispheric lateralization for language production and its relationships with manual preference and manual preference strength were studied in a sample of 297 subjects, including 153 left-handers (LH). A hemispheric functional lateralization index (HFLI) for language was derived from fMRI acquired during a covert sentence generation task as compared with a covert word list recitation. The multimodal HFLI distribution was optimally modeled using a mixture of 3 and 4 Gaussian functions in right-handers (RH) and LH, respectively. Gaussian function parameters helped to define 3 types of language hemispheric lateralization, namely "Typical" (left hemisphere dominance with clear positive HFLI values, 88% of RH, 78% of LH), "Ambilateral" (no dominant hemisphere with HFLI values close to 0, 12% of RH, 15% of LH) and "Strongly-atypical" (right-hemisphere dominance with clear negative HFLI values, 7% of LH). Concordance between dominant hemispheres for hand and for language did not exceed chance level, and most of the association between handedness and language lateralization was explained by the fact that all Strongly-atypical individuals were left-handed. Similarly, most of the relationship between language lateralization and manual preference strength was explained by the fact that Strongly-atypical individuals exhibited a strong preference for their left hand. These results indicate that concordance of hemispheric dominance for hand and for language occurs barely above the chance level, except in a group of rare individuals (less than 1% in the general population) who exhibit strong right hemisphere dominance for both language and their preferred hand. They call for a revisit of models hypothesizing common determinants for handedness and for language dominance.

  6. B800-B850 coherence correlates with energy transfer rates in the LH2 complex of photosynthetic purple bacteria.

    PubMed

    Smyth, Cathal; Oblinsky, Daniel G; Scholes, Gregory D

    2015-12-14

    Until recently, no analytical measure of many-body delocalization in open systems had been developed, yet such a measure enables characterization of how molecular excitons delocalize in photosynthetic light-harvesting complexes, and in turn helps us understand quantum coherent aspects of electronic energy transfer. In this paper we apply these measures to a model peripheral light-harvesting complex, LH2 from Rhodopseudomonas acidophila. We find how many chromophores collectively contribute to the "delocalization length" of an excitation within LH2 and how the coherent delocalization is distributed spatially. We also investigate to what extent this delocalization length is effective, by examining the impact of bipartite and multipartite entanglement in inter-ring energy transfer in LH2.

  7. Carotenoid stoichiometry in the LH2 crystal: no spectral evidence for the presence of the second molecule in the alpha/beta-apoprotein dimer.

    PubMed

    Gall, Andrew; Gardiner, Alastair T; Cogdell, Richard J; Robert, Bruno

    2006-07-10

    In this work we have investigated the carotenoid-protein interactions in LH2 complexes of Rhodopseudomonas acidophila both in "free in solution" mixed-micelles and in three-dimensional crystals by Raman spectroscopy in resonance with the carotenoid (Car) molecules. We show that the Car molecules when bound to their binding pockets show no significant differences when the complexes are "free in solution" or packed in crystalline arrays. Furthermore, there is no significant wavelength dependence in the Raman spectrum of the Car molecules of LH2. This indicates that there is only one Car configuration in LH2 and thus only one molecule per alpha/beta-heterodimer.

  8. Singlet-triplet fission of carotenoid excitation in light-harvesting LH2 complexes of purple phototrophic bacteria.

    PubMed

    Klenina, I B; Makhneva, Z K; Moskalenko, A A; Gudkov, N D; Bolshakov, M A; Pavlova, E A; Proskuryakov, I I

    2014-03-01

    The current generally accepted structure of light-harvesting LH2 complexes from purple phototrophic bacteria conflicts with the observation of singlet-triplet carotenoid excitation fission in these complexes. In LH2 complexes from the purple bacterium Allochromatium minutissimum, a drop in the efficiency of carotenoid triplet generation is demonstrated, which correlates with the extent of selective photooxidation of bacteriochlorophylls absorbing at ~850 nm. We conclude that singlet-triplet fission of carotenoid excitation proceeds with participation of these excitonically coupled bacteriochlorophylls. In the framework of the proposed mechanism, the contradiction between LH2 structure and photophysical properties of carotenoids is eliminated. The possibility of singlet-triplet excitation fission involving a third mediator molecule was not considered earlier.

  9. Vehicle-scale investigation of a fluorine jet-pump liquid hydrogen tank pressurization system

    NASA Technical Reports Server (NTRS)

    Cady, E. C.; Kendle, D. W.

    1972-01-01

    A comprehensive analytical and experimental program was performed to evaluate the performance of a fluorine-hydrogen jet-pump injector for main tank injection (MTI) pressurization of a liquid hydrogen (LH2) tank. The injector performance during pressurization and LH2 expulsion was determined by a series of seven tests of a full-scale injector and MTI pressure control system in a 28.3 cu m (1000 cu ft) flight-weight LH2 tank. Although the injector did not effectively jet-pump LH2 continuously, it showed improved pressurization performance compared to straight-pipe injectors tested under the same conditions in a previous program. The MTI computer code was modified to allow performance prediction for the jet-pump injector.

  10. A Patient Friendly Corifollitropin Alfa Protocol without Routine Pituitary Suppression in Normal Responders

    PubMed Central

    Wang, Huai-Ling; Lai, Hsing-Hua; Chuang, Tzu-Hsuan; Shih, Yu-Wei; Huang, Shih-Chieh; Lee, Meng-Ju; Chen, Shee-Uan

    2016-01-01

    The release of corifollitropin alfa simplifies daily injections of short-acting recombinant follicular stimulating hormone (rFSH), and its widely-used protocol involves short-acting gonadotropins supplements and a fixed GnRH antagonist regimen, largely based on follicle size. In this study, the feasibility of corifollitropin alfa without routine pituitary suppression was evaluated. A total of 288 patients were stimulated by corifollitropin alfa on cycle day 3 following with routine serum hormone monitoring and follicle scanning every other day after 5 days of initial stimulation, and a GnRH antagonist (0.25 mg) was only used prophylactically when the luteinizing hormone (LH) was ≧ 6 IU/L (over half of the definitive LH surge). The incidence of premature LH surge (≧ 10 IU/L) was 2.4% (7/288) before the timely injection of a single GnRH antagonist, and the elevated LH level was dropped down from 11.9 IU/L to 2.2 IU/L after the suppression. Two hundred fifty-one patients did not need any antagonist (87.2% [251/288]) throughout the whole stimulation. No adverse effects were observed regarding oocyte competency (fertilization rate: 78%; blastocyst formation rate: 64%). The live birth rate per OPU cycle after the first cryotransfer was 56.3% (161/286), and the cumulative live birth rate per OPU cycle after cyrotransfers was 69.6% (199/286). Of patients who did and did not receive GnRH antagonist during stimulation, no significant difference existed in the cumulative live birth rates (78.4% vs. 68.3%, p = 0.25). The results demonstrated that the routine GnRH antagonist administration is not required in the corifollitropin-alfa cycles using a flexible and hormone-depended antagonist regimen, while the clinical outcome is not compromised. This finding reveals that the use of a GnRH antagonist only occasionally may be needed. PMID:27100388

  11. A Patient Friendly Corifollitropin Alfa Protocol without Routine Pituitary Suppression in Normal Responders.

    PubMed

    Wang, Huai-Ling; Lai, Hsing-Hua; Chuang, Tzu-Hsuan; Shih, Yu-Wei; Huang, Shih-Chieh; Lee, Meng-Ju; Chen, Shee-Uan

    2016-01-01

    The release of corifollitropin alfa simplifies daily injections of short-acting recombinant follicular stimulating hormone (rFSH), and its widely-used protocol involves short-acting gonadotropins supplements and a fixed GnRH antagonist regimen, largely based on follicle size. In this study, the feasibility of corifollitropin alfa without routine pituitary suppression was evaluated. A total of 288 patients were stimulated by corifollitropin alfa on cycle day 3 following with routine serum hormone monitoring and follicle scanning every other day after 5 days of initial stimulation, and a GnRH antagonist (0.25 mg) was only used prophylactically when the luteinizing hormone (LH) was ≧ 6 IU/L (over half of the definitive LH surge). The incidence of premature LH surge (≧ 10 IU/L) was 2.4% (7/288) before the timely injection of a single GnRH antagonist, and the elevated LH level was dropped down from 11.9 IU/L to 2.2 IU/L after the suppression. Two hundred fifty-one patients did not need any antagonist (87.2% [251/288]) throughout the whole stimulation. No adverse effects were observed regarding oocyte competency (fertilization rate: 78%; blastocyst formation rate: 64%). The live birth rate per OPU cycle after the first cryotransfer was 56.3% (161/286), and the cumulative live birth rate per OPU cycle after cyrotransfers was 69.6% (199/286). Of patients who did and did not receive GnRH antagonist during stimulation, no significant difference existed in the cumulative live birth rates (78.4% vs. 68.3%, p = 0.25). The results demonstrated that the routine GnRH antagonist administration is not required in the corifollitropin-alfa cycles using a flexible and hormone-depended antagonist regimen, while the clinical outcome is not compromised. This finding reveals that the use of a GnRH antagonist only occasionally may be needed.

  12. Astronomy. ASASSN-15lh: A highly super-luminous supernova.

    PubMed

    Dong, Subo; Shappee, B J; Prieto, J L; Jha, S W; Stanek, K Z; Holoien, T W-S; Kochanek, C S; Thompson, T A; Morrell, N; Thompson, I B; Basu, U; Beacom, J F; Bersier, D; Brimacombe, J; Brown, J S; Bufano, F; Chen, Ping; Conseil, E; Danilet, A B; Falco, E; Grupe, D; Kiyota, S; Masi, G; Nicholls, B; Olivares E, F; Pignata, G; Pojmanski, G; Simonian, G V; Szczygiel, D M; Woźniak, P R

    2016-01-15

    We report the discovery of ASASSN-15lh (SN 2015L), which we interpret as the most luminous supernova yet found. At redshift z = 0.2326, ASASSN-15lh reached an absolute magnitude of Mu ,AB = -23.5 ± 0.1 and bolometric luminosity Lbol = (2.2 ± 0.2) × 10(45) ergs s(-1), which is more than twice as luminous as any previously known supernova. It has several major features characteristic of the hydrogen-poor super-luminous supernovae (SLSNe-I), whose energy sources and progenitors are currently poorly understood. In contrast to most previously known SLSNe-I that reside in star-forming dwarf galaxies, ASASSN-15lh appears to be hosted by a luminous galaxy (MK ≈ -25.5) with little star formation. In the 4 months since first detection, ASASSN-15lh radiated (1.1 ± 0.2) × 10(52) ergs, challenging the magnetar model for its engine. Copyright © 2016, American Association for the Advancement of Science.

  13. Highly potent metallopeptide analogues of luteinizing hormone-releasing hormone.

    PubMed Central

    Bajusz, S; Janaky, T; Csernus, V J; Bokser, L; Fekete, M; Srkalovic, G; Redding, T W; Schally, A V

    1989-01-01

    Metal complexes related to the cytotoxic complexes cisplatin [cis-diamminedichloroplatinum(II)] and transbis(salicylaldoximato)copper(II) were incorporated into suitably modified luteinizing hormone-releasing hormone (LH-RH) analogues containing D-lysine at position 6. Some of the metallopeptides thus obtained proved to be highly active LH-RH agonists or antagonists. For instance, SB-40, a PtCl2-containing metallopeptide in which platinum is coordinated to an N epsilon-(DL-2,3-diaminopropionyl)-D-lysine residue [D-Lys(DL-A2pr] at position 6, showed 50 times higher LH-releasing potency than the native hormone. SB-95, [Ac-D-Nal(2)1,D-Phe(pCl)2, D-Pal(3)2, Arg5,D-Lys[DL-A2pr(Sal2Cu)]6,D-Ala10]LH-RH, where Nal(2) is 3-(2-naphthyl)alanine, Pal(3) is 3-(3-pyridyl)alanine, and copper(II) is coordinated to the salicylideneimino moieties resulting from condensation of salicylaldehyde with D-Lys(DL-A2pr)6, caused 100% inhibition of ovulation at a dose of 3 micrograms in rats. Most metallopeptide analogues of LH-RH showed high affinities for the membrane receptors of rat pituitary and human breast cancer cells. Some of these metallopeptides had cytotoxic activity against human breast cancer and prostate cancer cell lines in vitro (this will be the subject of a separate paper on cytotoxicity evaluation). Such cytostatic metallopeptides could be envisioned as targeted chemotherapeutic agents in cancers that contain receptors for LH-RH-like peptides. PMID:2548206

  14. Highly potent metallopeptide analogues of luteinizing hormone-releasing hormone.

    PubMed

    Bajusz, S; Janaky, T; Csernus, V J; Bokser, L; Fekete, M; Srkalovic, G; Redding, T W; Schally, A V

    1989-08-01

    Metal complexes related to the cytotoxic complexes cisplatin [cis-diamminedichloroplatinum(II)] and transbis(salicylaldoximato)copper(II) were incorporated into suitably modified luteinizing hormone-releasing hormone (LH-RH) analogues containing D-lysine at position 6. Some of the metallopeptides thus obtained proved to be highly active LH-RH agonists or antagonists. For instance, SB-40, a PtCl2-containing metallopeptide in which platinum is coordinated to an N epsilon-(DL-2,3-diaminopropionyl)-D-lysine residue [D-Lys(DL-A2pr] at position 6, showed 50 times higher LH-releasing potency than the native hormone. SB-95, [Ac-D-Nal(2)1,D-Phe(pCl)2, D-Pal(3)2, Arg5,D-Lys[DL-A2pr(Sal2Cu)]6,D-Ala10]LH-RH, where Nal(2) is 3-(2-naphthyl)alanine, Pal(3) is 3-(3-pyridyl)alanine, and copper(II) is coordinated to the salicylideneimino moieties resulting from condensation of salicylaldehyde with D-Lys(DL-A2pr)6, caused 100% inhibition of ovulation at a dose of 3 micrograms in rats. Most metallopeptide analogues of LH-RH showed high affinities for the membrane receptors of rat pituitary and human breast cancer cells. Some of these metallopeptides had cytotoxic activity against human breast cancer and prostate cancer cell lines in vitro (this will be the subject of a separate paper on cytotoxicity evaluation). Such cytostatic metallopeptides could be envisioned as targeted chemotherapeutic agents in cancers that contain receptors for LH-RH-like peptides.

  15. Development status of LE-7 fuel turbopump

    NASA Astrophysics Data System (ADS)

    Nakano, T.; Nagao, R.; Ohta, T.; Warashina, S.; Watanabe, H.; Oguchi, H.

    The liquid hydrogen turbopump (LH2 T/P) for the LE-7 engine has been developed since 1984. The component PDR was held in June 1988 and the basic troubles occurred at the development test were solved. Next, the component CDR-1 was held in December 1989 in order to feed back the test results of prototype LH2 T/P model to the design of qualification phase T/P. So, the production of these turbopumps was admitted. Recently, the component CDR-2 was held in February 1992 to reflect the counterparts adopted for some troubles (impeller and turbine blade cracks and so on) in long-time engine tests to the design of qualification phase T/P. In the qualification phase, the hydraulic characteristics and strength in the engine operating range were examined at the LH2 T/P component test, and its endurance confirmed at the engine tests. The LH2 turbopump component test was held at NASDA Kakuda and the engine test at Tashiro and Tanegashima. This paper describes the development status of LH2 T/P, containing the design description and the content of some troubles and its counterplans.

  16. Hypogonadism in DM1 and its relationship to erectile dysfunction.

    PubMed

    Antonini, Giovanni; Clemenzi, Alessandro; Bucci, Elisabetta; De Marco, Emanuela; Morino, Stefania; Di Pasquale, Antonella; Latino, Pamela; Ruga, Gilda; Lenzi, Andrea; Vanacore, Nicola; Radicioni, Antonio F

    2011-07-01

    Myotonic dystrophy type 1 (DM1) is characterized by both a premature appearance of age-related phenotypes and multiple organ involvement, which affects skeletal and smooth muscle as well as the eye, heart, central nervous system, and endocrine system. Although erectile dysfunction (ED) is a frequent complaint in patients with DM1, it has not been investigated in great depth. Hypogonadism, which is reported to be one of the physical causes of ED in the general population, frequently occurs in DM1. We planned this case-control study to evaluate the relationship between hypogonadism, as defined by the sexual hormone profile (FSH, LH, testosterone (T) and prolactin) and ED, as assessed by means of an internationally validated self-administered questionnaire (IIEF). DM1 patients had significantly increased mean levels of both gonadotropins (FSH and LH) (p < 0.0001) and a reduced mean level of T (p < 0.0001) when compared to controls. Twelve patients were eugonadic (normal LH, T, and FSH), while 18 displayed hormonal evidence of hypogonadism, characterized by tubular failure (increased FSH) in all the subjects and associated with interstitial failure in 14 subjects: seven with primary hypogonadism (increased LH and reduced T) and seven with compensated hypogonadism (increased LH and normal T). Patients with hormonal evidence of interstitial failure had a larger CTG expansion (p = 0.008), longer disease duration (p = 0.013), higher grade of disease (p = 0.004) and lower erectile function score (p = 0.02) than eugonadic patients. Impotence occurred in 13/14 hypogonadic patients with interstitial failure and in 5/12 eugonadic patients (p = 0.017, OR = 18.2).

  17. A comparative integrated transcript analysis and functional characterization of differential mechanisms for induction of liver hypertrophy in the rat

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Boitier, Eric, E-mail: eric.boitier@sanofi-aventis.com; Amberg, Alexander; Barbie, Valerie

    2011-04-15

    The main goal of the present work was to better understand the molecular mechanisms underlying liver hypertrophy (LH), a recurrent finding observed following acute or repeated drug administration to animals, using transcriptomic technologies together with the results from conventional toxicology methods. Administration of 5 terminated proprietary drug candidates from participating companies involved in the EU Innomed PredTox Project or the reference hepatotoxicant troglitazone to rats for up to a 14-day duration induced LH as the main liver phenotypic toxicity outcome. The integrated analysis of transcriptomic liver expression data across studies turned out to be the most informative approach for themore » generation of mechanistic models of LH. In response to a xenobiotic stimulus, a marked increase in the expression of xenobiotic metabolizing enzymes (XME) was observed in a subset of 4 studies. Accumulation of these newly-synthesized proteins within the smooth endoplasmic reticulum (SER) would suggest proliferation of this organelle, which most likely is the main molecular process underlying the LH observed in XME studies. In another subset of 2 studies (including troglitazone), a marked up-regulation of genes involved in peroxisomal fatty acid {beta}-oxidation was noted, associated with induction of genes involved in peroxisome proliferation. Therefore, an increase in peroxisome abundance would be the main mechanism underlying LH noted in this second study subset. Together, the use of transcript profiling provides a means to generate putative mechanistic models underlying the pathogenesis of liver hypertrophy, to distinguish between subtle variations in subcellular organelle proliferation and creates opportunities for improved mechanism-based risk assessment.« less

  18. Redirecting intracellular trafficking and the secretion pattern of FSH dramatically enhances ovarian function in mice.

    PubMed

    Wang, Huizhen; Larson, Melissa; Jablonka-Shariff, Albina; Pearl, Christopher A; Miller, William L; Conn, P Michael; Boime, Irving; Kumar, T Rajendra

    2014-04-15

    FSH and luteinizing hormone (LH) are secreted constitutively or in pulses, respectively, from pituitary gonadotropes in many vertebrates, and regulate ovarian function. The molecular basis for this evolutionarily conserved gonadotropin-specific secretion pattern is not understood. Here, we show that the carboxyterminal heptapeptide in LH is a gonadotropin-sorting determinant in vivo that directs pulsatile secretion. FSH containing this heptapeptide enters the regulated pathway in gonadotropes of transgenic mice, and is released in response to gonadotropin-releasing hormone, similar to LH. FSH released from the LH secretory pathway rescued ovarian defects in Fshb-null mice as efficiently as constitutively secreted FSH. Interestingly, the rerouted FSH enhanced ovarian follicle survival, caused a dramatic increase in number of ovulations, and prolonged female reproductive lifespan. Furthermore, the rerouted FSH vastly improved the in vivo fertilization competency of eggs, their subsequent development in vitro and when transplanted, the ability to produce offspring. Our study demonstrates the feasibility to fine-tune the target tissue responses by modifying the intracellular trafficking and secretory fate of a pituitary trophic hormone. The approach to interconvert the secretory fate of proteins in vivo has pathophysiological significance, and could explain the etiology of several hormone hyperstimulation and resistance syndromes.

  19. Evaluation of Learned Helplessness, Perceived Self-efficacy, and Functional Capacity in Patients With Fibromyalgia and Rheumatoid Arthritis.

    PubMed

    Moyano, Sebastián; Scolnik, Marina; Vergara, Facundo; García, María Victoria; Sabelli, Mirtha Rosa; Rosa, Javier Eduardo; Catoggio, Luis José; Soriano, Enrique Roberto

    2018-03-19

    The aims of this study were to compare learned helplessness (LH) and perceived self-efficacy (SE) in patients with fibromyalgia (FM) and rheumatoid arthritis (RA) and to assess their correlation with functional disability, level of perceived pain, and fatigue. This multicenter, cross-sectional study included consecutive patients (aged ≥18 years) with RA, according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria, and FM, according to 2010 American College of Rheumatology criteria. Learned helplessness was measured by the Rheumatology Attitude Index, Spanish version; SE with the Arthritis Self-efficacy Scale, Spanish version; functional capacity with the Health Assessment Questionnaire (HAQ), Argentine version; depression with Center for Epidemiological Studies-Depression Scale 7-item version and perceived pain and fatigue by the visual analog scale. Disease activity was measured by the Clinical Disease Activity Index (CDAI) and disease impact with the Fibromyalgia Impact Questionnaire (FIQ). A total of 215 patients, 100 with FM and 115 with RA, were included. Mean age was 59 (SD, 14) years and 58 (SD, 13) years for FM and RA, patients respectively. Whereas LH and depression were significantly higher, SE was significantly lower in FM patients. We found a positive correlation between LH and HAQ, pain, depression, fatigue, FIQ, and CDAI in FM and RA patients. We observed a negative correlation between SE and HAQ, pain, depression, fatigue, FIQ (FM), and CDAI (RA) in both groups. Both LH and SE correlate significantly with functional capacity, perceived pain, disease activity, and disease impact in RA and FM patients. Learned helplessness was higher in patients with active disease or high disease impact, as opposed to those in remission or with low disease impact, and the reverse was true for SE. Patients with FM had significantly more LH, pain, fatigue, and depression and less SE compared with those with RA.

  20. Modulatory effects of l-carnitine plus l-acetyl-carnitine on neuroendocrine control of hypothalamic functions in functional hypothalamic amenorrhea (FHA).

    PubMed

    Genazzani, Alessandro D; Despini, Giulia; Czyzyk, Adam; Podfigurna, Agnieszka; Simoncini, Tommaso; Meczekalski, Blazej

    2017-12-01

    Functional hypothalamic amenorrhea (FHA) is a relatively frequent disease due to the combination of metabolic, physical, or psychological stressors. It is characterized by the low endogenous GnRH-induced gonadotropin secretion, thus triggering the ovarian blockade and a hypoestrogenic condition. Up to now various therapeutical strategies have been proposed, both using hormonal treatment as well as neuroactive compounds. Since carnitine, namely l-acetyl-carnitine (LAC), has been demonstrated to be effective in the modulation of the central hypothalamic control of GnRH secretion, we aimed to evaluate whether a combined integrative treatment for 12 weeks of LAC (250 mg/die) and l-carnitine (500 mg/die) was effective in improving the endocrine and metabolic pathways in a group of patients (n = 27) with FHA. After the treatment, interval mean LH plasma levels increased while those of cortisol and amylase decreased significantly. When patients were subdivided according to baseline LH levels, only hypo-LH patients showed the significant increase of LH plasma levels and the significant decrease of both cortisol and amylase plasma levels. The increased 17OHP/cortisol ratio, as index of the adrenal activity, demonstrated the reduced stress-induced adrenal activity. In conclusion, our data sustain the hypothesis that the integrative administration of LAC plus l-carnitine reduced both the metabolic and the neuroendocrine impairment of patients with FHA.

  1. Where Have I Been? Where Should I Go? Spatial Working Memory on a Radial Arm Maze in a Rat Model of Depression

    PubMed Central

    Richter, Sophie Helene; Zeuch, Benjamin; Lankisch, Katja; Gass, Peter; Durstewitz, Daniel; Vollmayr, Barbara

    2013-01-01

    Disturbances in cognitive functioning are among the most debilitating problems experienced by patients with major depression. Investigations of these deficits in animals help to extend and refine our understanding of human emotional disorder, while at the same time providing valid tools to study higher executive functions in animals. We employ the “learned helplessness” genetic rat model of depression in studying working memory using an eight arm radial maze procedure with temporal delay. This so-called delayed spatial win-shift task consists of three phases, training, delay and test, requiring rats to hold information on-line across a retention interval and making choices based on this information in the test phase. According to a 2×2 factorial design, working memory performance of thirty-one congenitally helpless (cLH) and non-helpless (cNLH) rats was tested on eighteen trials, additionally imposing two different delay durations, 30 s and 15 min, respectively. While not observing a general cognitive deficit in cLH rats, the delay length greatly influenced maze performance. Notably, performance was most impaired in cLH rats tested with the shorter 30 s delay, suggesting a stress-related disruption of attentional processes in rats that are more sensitive to stress. Our study provides direct animal homologues of clinically important measures in human research, and contributes to the non-invasive assessment of cognitive deficits associated with depression. PMID:23614050

  2. Space Shuttle - Bringing cryohydrogen technology down to earth. [details of LH2 and LO2 technology and External Tank design

    NASA Technical Reports Server (NTRS)

    Odom, J. B.

    1978-01-01

    The External Tank must provide a safe storage container for both LH2 and LO2, a means of maintaining propellant quality in order to meet the engine pump net positive suction pressure requirements, and a structural strong-back for the Space Shuttle system, all at the minimum recurring cost and weight, while maintaining quality and reliability. The present paper summarizes External Tank design features and discusses the advantages of using LH2 and LO2 for the Space Shuttle system.

  3. Impact of thyroid function abnormalities on reproductive hormones during menstrual cycle in premenopausal HIV infected females at NAUTH, Nnewi, Nigeria

    PubMed Central

    Emelumadu, Obiageli Fidelia; Igwegbe, Anthony Osita; Monago, Ifeoma Nwamaka; Ilika, Amobi Linus

    2017-01-01

    Background This was a prospective study designed to evaluate the impact of thyroid function abnormalities on reproductive hormones during menstrual cycle in HIV infected females at Nnamdi Azikiwe University Teaching Hospital Nnewi, South-East Nigeria. Methods The study randomly recruited 35 Symptomatic HIV infected females and 35 Symptomatic HIV infected females on antiretroviral therapy (HAART) for not less than six weeks from an HIV clinic and 40 apparently heathy control females among the hospital staff of NAUTH Nnewi. They were all premenopausal females with regular menstrual cycle and aged between 15–45 years. Blood samples were collected at follicular and luteal phases of their menstrual cycle for assay of Thyroid indices (FT3, FT4 and TSH) and Reproductive indices (FSH, LH, Estrogen, Progesterone, Prolactin and Testosterone) using ELISA method. Results The result showed significantly higher FSH and LH but significantly lower progesterone (prog) and estrogen (E2) in the test females compared to control females at both phases of menstrual cycle (P<0.05). There was significantly lower FT3 but significantly higher TSH value in Symptomatic HIV females (P<0.05). FSH, LH and TSH values were significantly lowered while prog and FT3 were significantly higher in Symptomatic HIV on ART compared to Symptomatic HIV females (P<0.05). FT3, FT4, Prog and E2 were inversely correlated while FSH and LH were positively correlated with duration of HIV infection in HIV females (P<0.05 respectively). There was a direct correlation between CD4+ count and FT3 while inverse correlation was found between CD4+ count and TSH levels (P<0.05). Discussion The present study demonstrated hypothyroidism with a significant degree of primary hypogonadism in Symptomatic HIV infected females at both follicular and luteal phases of menstrual cycle which tends to normalize on treatments. PMID:28723963

  4. Hypokalemia decreases testosterone production in male mice by altering luteinizing hormone secretion.

    PubMed

    Sánchez-Capelo, A; Castells, M T; Cremades, A; Peñafiel, R

    1996-09-01

    Potassium deficiency produced by feeding mice a low potassium diet caused a marked decrease in plasma and testicular testosterone concentrations and a concomitant fall in the weight of seminal vesicles and in renal ornithine decarboxylase activity. All of these parameters were rapidly restored when potassium supply was normalized. Immunocytochemical analysis of gonadotropes and plasma LH values suggested that the pulsatile liberation of LH by the pituitary was impaired in the potassium-deficient male mice. Because the synthesis of testosterone in the potassium-deficient mice was stimulated by exogenous LH, hCG, or GnRH, one can conclude that alteration of the transcellular potassium gradient could affect the regulation of the hypothalamo-hypophyseal-testicular axis by affecting the pulsatile release of GnRH. Our results showing that the stimulation of LH secretion after castration was similar in control and potassium-deficient male mice suggest that a testicular factor(s) different from testosterone could be implicated in the abnormal regulation of LH secretion in potassium-deficient mice. We conclude that plasma potassium concentration is an important factor in the regulation of gonadotropin secretion and testicular functions.

  5. [Severe postmenopausal hyperandrogenism due to an ovarian lipoid cell tumor: a case report].

    PubMed

    Bernasconi, D; Del Monte, P; Marinaro, E; Marugo, A; Marugo, M

    2004-03-01

    The case of a 62-year-old woman with severe post-menopausal hirsutism is described. Her clinical history revealed regular menstrual periods until menopause at the age of 50, hysterectomy for fibromatosis at 58 years, non-insulin dependent diabetes mellitus, hypertension, obesity, severe hirsutism, which had developed in the previous 3 years, with a deeping of the voice. Examination showed android obesity, hypertension and severe hirsutism involving the face and the trunk. Endocrine evaluation pointed out regular adrenal function, serum total and free-testosterone in the adult male range, with normal androstenedione, DHEAS and 17OHP levels. Estradiol was slightly increased and LH and FSH were inappropriately low for her post-menopausal age. Computed tomography of the abdomen showed regular adrenal glands, and a radio-labeled cholesterol scan was negative. A further pelvic transvaginal ultrasonography revealed a small cystic formation near the right ovary and a slight increase in the size of the left ovary. The patient underwent bilateral ovariectomy. Histological examination showed a lipoid cell tumor within the left ovary. Immunohistochemical studies were positive for inhibin and cytokeratin. After surgery, serum testosterone fell to normal levels, gonadotropins increased to menopausal levels, confirming that the tumor was able to produce both LH, and FSH-inhibiting factors, and hirsutism greatly improved. Periodic hormonal tests remained normal and CT of the abdomen and pelvic ultrasonography did not show alterations at a 3 years follow-up.

  6. Neurokinin-3 Receptor Activation in the Retrochiasmatic Area is Essential for the Full Preovulatory LH Surge in Ewes

    PubMed Central

    Porter, Katrina L.; Hileman, Stanley M.; Hardy, Steven L.; Nestor, Casey C; Lehman, Michael N.; Goodman, Robert L.

    2014-01-01

    Neurokinin B (NKB) is essential for human reproduction and has been shown to stimulate LH secretion in several species, including sheep. Ewes express the neurokinin-3 receptor (NK3R) in the retrochiasmatic area (RCh) and there is one report that placement of senktide, an NK3R agonist, therein stimulates LH secretion that resembles an LH surge in ewes. In this study, we first confirmed that local administration of senktide to the RCh produced a surge-like increase in LH secretion, and then tested the effects of this agonist in two other areas implicated in the control of LH secretion and where NK3R is found in high abundance: the preoptic area (POA) and arcuate nucleus (ARC). Bilateral microimplants containing senktide induced a dramatic surge-like increase in LH when given in the POA similar to that seen with RCh treatment. In contrast, senktide treatment in the ARC resulted in a much smaller, but significant, increase in LH concentrations suggestive of an effect on tonic secretion. The possible role of POA and RCh NK3R activation in the LH surge was next tested by treating ewes with SB222200, an NK3R antagonist, in each area during an E2-induced LH surge. SB222200 in the RCh, but not in the POA, reduced LH surge amplitude by about 40% compared to controls, indicating that NK3R activation in the former region is essential for full expression of the preovulatory LH surge. Based on these data, we propose that NKB actions in the RCh are an important component of the preovulatory LH surge in ewes. PMID:25040132

  7. Integration of energy and electron transfer processes in the photosynthetic membrane of Rhodobacter sphaeroides

    DOE PAGES

    Cartron, Michaël L.; Olsen, John D.; Sener, Melih; ...

    2014-02-13

    Photosynthesis converts absorbed solar energy to a protonmotive force, which drives ATP synthesis. The membrane network of chlorophyll–protein complexes responsible for light absorption, photochemistry and quinol (QH 2) production has been mapped in the purple phototrophic bacterium Rhodobacter (Rba.) sphaeroides using atomic force microscopy (AFM), but the membrane location of the cytochrome bc 1 (cytbc 1) complexes that oxidise QH 2 to quinone (Q) to generate a protonmotive force is unknown. We labelled cytbc 1 complexes with gold nanobeads, each attached by a Histidine 10 (His 10)-tag to the C-terminus of cytc1. Electron microscopy (EM) of negatively stained chromatophore vesiclesmore » showed that the majority of the cytbc 1 complexes occur as dimers in the membrane. The cytbc 1 complexes appeared to be adjacent to reaction centre light-harvesting 1-PufX (RC-LH1-PufX) complexes, consistent with AFM topographs of a gold-labelled membrane. His-tagged cytbc1 complexes were retrieved from chromatophores partially solubilised by detergent; RC-LH1-PufX complexes tended to co-purify with cytbc 1, whereas LH2 complexes became detached, consistent with clusters of cytbc1 complexes close to RC-LH1-PufX arrays, but not with a fixed, stoichiometric cytbc 1-RC-LH1- PufX supercomplex. This information was combined with a quantitative mass spectrometry (MS) analysis of the RC, cytbc 1, ATP synthase, cytaa 3 and cytcbb 3 membrane protein complexes, to construct an atomic-level model of a chromatophore vesicle comprising 67 LH2 complexes, 11 LH1-RC-PufX dimers & 2 RC-LH1-PufX monomers, 4 cytbc 1 dimers and 2 ATP synthases. In conclusion, simulation of the interconnected energy, electron and proton transfer processes showed a halfmaximal ATP turnover rate for a light intensity equivalent to only 1% of bright sunlight. Thus, the photosystem architecture of the chromatophore is optimised for growth at low light intensities.« less

  8. Hypogonadism in a patient with two novel mutations of the luteinizing hormone β-subunit gene expressed in a compound heterozygous form.

    PubMed

    Basciani, Sabrina; Watanabe, Mikiko; Mariani, Stefania; Passeri, Marina; Persichetti, Agnese; Fiore, Daniela; Scotto d'Abusco, Anna; Caprio, Massimiliano; Lenzi, Andrea; Fabbri, Andrea; Gnessi, Lucio

    2012-09-01

    LH gene mutations are rare; only four mutations have been described. The affected individuals are hypogonadal. We describe the clinical features of a 31-yr-old man who presented with delayed puberty and azoospermia and was found to have hypogonadism associated with an absence of circulating LH. The patient had a 12-bp deletion in exon 2 in the LH β-subunit gene and a mutation of the 5' splice site IVS2+1G→T in the same gene present in a compound heterozygous state. The first mutation predicts a deletion of four leucines of the hydrophobic core of the signal peptide. The second mutation disrupts the splicing of mRNA, generating a gross abnormality in the processing. The patient's heterozygous parents were clinically normal. The phenotype of a 16-yr-old sister of the proband, carrying the same mutations, was characterized by normal pubertal development and oligomenorrhea. This report unravels two novel mutations of the LH gene critical for synthesis and activity of the LH molecule. The insight gained from the study is that normal pubertal maturation in women can occur in a state of LH deficiency, whereas LH is essential for maturation of Leydig cells and thus steroidogenesis, puberty, and spermatogenesis in man. These mutations should be considered in girls and boys with selective deficiency of LH.

  9. Effect of human gonadotropins on spermiation and androgen biosynthesis in the testis of the toad Bufo arenarum (Amphibia, Anura).

    PubMed

    Pozzi, Andrea Gabriela; Rosemblit, Cinthia; Ceballos, Nora Raquel

    2006-01-01

    This paper analyzes, in the toad Bufo arenarum, the effect on spermiation and androgen secretion of two human recombinant gonadotropins, human recombinant LH (hrLH) and human recombinant FSH (hrFSH) as well as the well-known spermiation-inducing hormone, human chorionic gonadotropin (hCG). For this purpose, testes were incubated with different concentrations of hrLH (0.01-2.5 microg/ml) and hrFSH (0.05-5 microg/ml), and results were compared with those obtained with 2.5 microg/ml hCG. Spermiation was most efficiently stimulated by hrFSH, which elicited a higher response than either hrLH or hCG. Both hrFSH and hrLH produced a bell-shaped dose-response curve, with a 50% inhibition on spermiation at a concentration twice higher than that necessary to get the highest response. However, none of the gonadotropins yielded a biphasic response on androgen secretion, hrLH producing the highest response at a concentration that evoked a 70% inhibition in the spermiation test. Regarding steroidogenesis, hrLH and hrFSH were more active than hCG. Taken together, the results described in this paper suggest that, in B. arenarum, spermiation and androgen secretion are mediated by different receptors. After comparing the effects of recombinant hormones, we conclude that hrFSH has a greater effect on spermiation than hCG or hrLH.

  10. Reduced connectivity and inter-hemispheric symmetry of the sensory system in a rat model of vulnerability to developing depression.

    PubMed

    Ben-Shimol, E; Gass, N; Vollmayr, B; Sartorius, A; Goelman, G

    2015-12-03

    Defining the markers corresponding to a high risk of developing depression in humans would have major clinical significance; however, few studies have been conducted since they are not only complex but also require homogeneous groups. This study compared congenital learned helpless (cLH) rats, selectively bred for high stress sensitivity and learned helplessness (LH) behavior, to congenital non-learned helpless (cNLH) rats that were bred for resistance to uncontrollable stress. Naïve cLH rats show some depression-like behavior but full LH behavior need additional stress, making this model ideal for studying vulnerability to depression. Resting-state functional connectivity obtained from seed correlation analysis was calculated for multiple regions that were selected by anatomy AND by a data-driven approach, independently. Significance was determined by t-statistic AND by permutation analysis, independently. A significant reduction in functional connectivity was observed by both analyses in the cLH rats in the sensory, motor, cingulate, infralimbic, accumbens and the raphe nucleus. These reductions corresponded primarily to reduced inter-hemispheric connectivity. The main reduction however was in the sensory system. It is argued that reduced connectivity and inter-hemispheric connectivity of the sensory system reflects an internal convergence state which may precede other depressive symptomatology and therefore could be used as markers for vulnerability to the development of depression. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Characterization of the homologous and heterologous desensitization of rat Leydig-tumour-cell adenylate cyclase.

    PubMed

    Dix, C J; Habberfield, A D; Cooke, B A

    1984-06-15

    The homologous and heterologous desensitization of rat Leydig-tumour-cell adenylate cyclase induced by lutropin (LH) was characterized with the aid of forskolin and cholera toxin. Forskolin stimulated cyclic AMP production in a dose-dependent manner, with linear kinetics up to 2h. Forskolin also potentiated the action of LH on cyclic AMP production, but was only additive with cholera toxin. Preincubation of rat Leydig tumour cells with LH (1.0 micrograms/ml) for 1 h produced a desensitization of the subsequent LH (1.0 micrograms/ml)-stimulated cyclic AMP production, whereas the responses to cholera toxin (5.0 micrograms/ml), forskolin (100 microM), LH plus forskolin or cholera toxin plus forskolin were unaltered. In contrast, preincubation with LH for 20h produced a desensitization to all the stimuli tested. When rat Leydig tumour cells were preincubated for 1h with forskolin or dibutyryl cyclic AMP, the only subsequent response that was significantly altered was that to LH plus forskolin after preincubation with forskolin. However, preincubation for 20h with forskolin or dibutyryl cyclic AMP induced a desensitization to all stimuli subsequently tested. LH produced a rapid (0-1h) homologous desensitization, which was followed by a slower (2-8h)-onset heterologous desensitization. Forskolin and dibutyryl cyclic AMP were only able to induce heterologous desensitization. The rate of desensitization induced by either forskolin or dibutyryl cyclic AMP was similar to the rate of heterologous desensitization induced by LH. These results demonstrate that in purified rat Leydig tumour cells LH produces an initial homologous desensitization of adenylate cyclase that involves a cyclic AMP-independent lesion at or proximal to the guanine nucleotide regulatory protein (G-protein). This is followed by heterologous desensitization, which can also be induced by forskolin or dibutyryl cyclic AMP, thus indicating that LH-induced heterologous desensitization of rat Leydig-tumour-cell adenylate cyclase involves a cyclic AMP-dependent lesion that is after the G-protein.

  12. Light absorption and excitation energy transfer calculations in primitive photosynthetic bacteria

    NASA Astrophysics Data System (ADS)

    Komatsu, Yu; Kayanuma, Megumi; Shoji, Mitsuo; Yabana, Kazuhiro; Shiraishi, Kenji; Umemura, Masayuki

    2015-06-01

    In photosynthetic organisms, light energy is converted into chemical energy through the light absorption and excitation energy transfer (EET) processes. These processes start in light-harvesting complexes, which contain special photosynthetic pigments. The exploration of unique mechanisms in light-harvesting complexes is directly related to studies, such as artificial photosynthesis or biosignatures in astrobiology. We examined, through ab initio calculations, the light absorption and EET processes using cluster models of light-harvesting complexes in purple bacteria (LH2). We evaluated absorption spectra and energy transfer rates using the LH2 monomer and dimer models to reproduce experimental results. After the calibration tests, a LH2 aggregation model, composed of 7 or 19 LH2s aligned in triangle lattice, was examined. We found that the light absorption is red shifted and the energy transfer becomes faster as the system size increases. We also found that EET is accelerated by exchanging the central pigments to lower energy excited pigments. As an astrobiological application, we calculated light absorptions efficiencies of the LH2 in different photoenvironments.

  13. Asthenospheric/Lithospheric interaction beneath Lianshan (Subei Basin, Eastern China)

    NASA Astrophysics Data System (ADS)

    Hao, Yantao; Bonadiman, Costanza; Coltorti, Massimo; Xia, Qunke

    2014-05-01

    This contribution presents the geochemical characterization of peridotite xenoliths entrained in Cenozoic alkali basalts from Lianshan (Subei Basin, Eastern China). The majority of the samples are lherzolites (lh) subdivided in three groups depending on the modal contents of clinopyroxene (cpx): cpx-poor lh (6

  14. Predicting hemispheric dominance for language production in healthy individuals using support vector machine.

    PubMed

    Zago, Laure; Hervé, Pierre-Yves; Genuer, Robin; Laurent, Alexandre; Mazoyer, Bernard; Tzourio-Mazoyer, Nathalie; Joliot, Marc

    2017-12-01

    We used a Support Vector Machine (SVM) classifier to assess hemispheric pattern of language dominance of 47 individuals categorized as non-typical for language from their hemispheric functional laterality index (HFLI) measured on a sentence minus word-list production fMRI-BOLD contrast map. The SVM classifier was trained at discriminating between Dominant and Non-Dominant hemispheric language production activation pattern on a group of 250 participants previously identified as Typicals (HFLI strongly leftward). Then, SVM was applied to each hemispheric language activation pattern of 47 non-typical individuals. The results showed that at least one hemisphere (left or right) was found to be Dominant in every, except 3 individuals, indicating that the "dominant" type of functional organization is the most frequent in non-typicals. Specifically, left hemisphere dominance was predicted in all non-typical right-handers (RH) and in 57.4% of non-typical left-handers (LH). When both hemisphere classifications were jointly considered, four types of brain patterns were observed. The most often predicted pattern (51%) was left-dominant (Dominant left-hemisphere and Non-Dominant right-hemisphere), followed by right-dominant (23%, Dominant right-hemisphere and Non-Dominant left-hemisphere) and co-dominant (19%, 2 Dominant hemispheres) patterns. Co-non-dominant was rare (6%, 2 Non-Dominant hemispheres), but was normal variants of hemispheric specialization. In RH, only left-dominant (72%) and co-dominant patterns were detected, while for LH, all types were found, although with different occurrences. Among the 10 LH with a strong rightward HFLI, 8 had a right-dominant brain pattern. Whole-brain analysis of the right-dominant pattern group confirmed that it exhibited a functional organization strictly mirroring that of left-dominant pattern group. Hum Brain Mapp 38:5871-5889, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. The stellar content of LH 9 and 10 (N11) in the LMC - A case for sequential star formation

    NASA Technical Reports Server (NTRS)

    Parker, Joel WM.; Garmany, Catharine D.; Massey, Philip; Walborn, Nolan R.

    1992-01-01

    The young OB associations Lucke-Hodge 9 and 10 are studied with UBV photometry that is independent of reddening to determine the IMF directly from star counts. The temperature and reddening of the stars are determined which, in conjunction with the spectroscopic classification of the earliest stars, is employed to place the stellar groups on the theoretical H-R diagram. Observations are also presented of the highly compact H II region/knot N11A and the multiple system HD 32228, and LH 9 and 10 are compared. The Lyman ionizing flux calculated at 4.9-7.2 x 10 exp 50/s agrees well with flux required to generate the H-alpha luminosity of the H II region. LH 10 has a much flatter slope, a higher ratio of higher-mass to lower-mass stars, and greater reddening than LH 9, and LH 10 contains all of the O stars earlier than O6. It is concluded that LH 9 is older than LH 10 and probably contributed to the initiation of star formation in LH 10.

  16. Immune status influences fear and anxiety responses in mice after acute stress exposure

    PubMed Central

    Clark, Sarah M.; Sand, Joseph; Francis, T. Chase; Nagaraju, Anitha; Michael, Kerry C.; Keegan, Achsah D.; Kusnecov, Alexander; Gould, Todd D.; Tonelli, Leonardo H.

    2014-01-01

    Significant evidence suggests that exposure to traumatic and/or acute stress in both mice and humans results in compromised immune function that in turn may affect associated brain processes. Additionally, recent studies in mouse models of immune deficiency have suggested that adaptive immunity may play a role during traumatic stress exposure and that impairments in lymphocyte function may contribute to increased susceptibility to various psychogenic stressors. However, rodent studies on the relationship between maladaptive stress responses and lymphocyte deficiency have been complicated by the fact that genetic manipulations in these models may also result in changes in CNS function due to the expression of targeted genes in tissues other than lymphocytes, including the brain. To address these issues we utilized mice with a deletion of recombination-activating gene 2 (Rag2), which has no confirmed expression in the CNS; thus, its loss should result in the absence of mature lymphocytes without altering CNS function directly. Stress responsiveness of immune deficient Rag2−/− mice on a BALB/c background was evaluated in three different paradigms: predator odor exposure (POE), fear conditioning (FC) and learned helplessness (LH). These models are often used to study different aspects of stress responsiveness after the exposure to an acute stressor. In addition, immunoblot analysis was used to assess hippocampal BDNF expression under both stressed and non-stressed conditions. Subsequent to POE, Rag2−/− mice exhibited a reduced acoustic startle response compared to BALB/c mice; no significant differences in behavior were observed in either FC or LH. Furthermore, analysis of hippocampal BDNF indicated that Rag2−/− mice have elevated levels of the mature form of BDNF compared to BALB/c mice. Results from our studies suggest that the absence of mature lymphocytes is associated with increased resilience to stress exposure in the POE and does not affect behavioral responses in the FC and LH paradigms. These findings indicate that lymphocytes play a specific role in stress responsiveness dependent upon the type, nature and intensity of the stressor. PMID:24524915

  17. Membrane development in purple photosynthetic bacteria in response to alterations in light intensity and oxygen tension.

    PubMed

    Niederman, Robert A

    2013-10-01

    Studies on membrane development in purple bacteria during adaptation to alterations in light intensity and oxygen tension are reviewed. Anoxygenic phototrophic such as the purple α-proteobacterium Rhodobacter sphaeroides have served as simple, dynamic, and experimentally accessible model organisms for studies of the photosynthetic apparatus. A major landmark in photosynthesis research, which dramatically illustrates this point, was provided by the determination of the X-ray structure of the reaction center (RC) in Blastochloris viridis (Deisenhofer and Michel, EMBO J 8:2149-2170, 1989), once it was realized that this represented the general structure for the photosystem II RC present in all oxygenic phototrophs. This seminal advance, together with a considerable body of subsequent research on the light-harvesting (LH) and electron transfer components of the photosynthetic apparatus has provided a firm basis for the current understanding of how phototrophs acclimate to alterations in light intensity and quality. Oxygenic phototrophs adapt to these changes by extensive thylakoid membrane remodeling, which results in a dramatic supramolecular reordering to assure that an appropriate flow of quinone redox species occurs within the membrane bilayer for efficient and rapid electron transfer. Despite the high level of photosynthetic unit organization in Rba. sphaeroides as observed by atomic force microscopy (AFM), fluorescence induction/relaxation measurements have demonstrated that the addition of the peripheral LH2 antenna complex in cells adapting to low-intensity illumination results in a slowing of the rate of electron transfer turnover by the RC of up to an order of magnitude. This is ascribed to constraints in quinone redox species diffusion between the RC and cytochrome bc1 complexes arising from the increased packing density as the intracytoplasmic membrane (ICM) bilayer becomes crowded with LH2 rings. In addition to downshifts in light intensity as a paradigm for membrane development studies in Rba. sphaeroides, the lowering of oxygen tension in chemoheterotropically growing cells results in a gratuitous formation of the ICM by an extensive membrane biogenesis process. These membrane alterations in response to lowered illumination and oxygen levels in purple bacteria are under the control of a number of interrelated two-component regulatory circuits reviewed here, which act at the transcriptional level to regulate the formation of both the pigment and apoprotein components of the LH, RC, and respiratory complexes. We have performed a proteomic examination of the ICM development process in which membrane proteins have been identified that are temporally expressed both during adaptation to low light intensity and ICM formation at low aeration and are spatially localized in both growing and mature ICM regions. For these proteomic analyses, membrane growth initiation sites and mature ICM vesicles were isolated as respective upper-pigmented band (UPB) and chromatophore fractions and subjected to clear native electrophoresis for isolation of bands containing the LH2 and RC-LH1 core complexes. In chromatophores, increasing levels of LH2 polypeptides relative to those of the RC-LH1 complex were observed as ICM membrane development proceeded during light-intensity downshifts, along with a large array of other associated proteins including high spectral counts for the F1FO-ATP synthase subunits and the cytochrome bc1 complex, as well as RSP6124, a protein of unknown function, that was correlated with increasing LH2 spectral counts. In contrast, the UPB was enriched in cytoplasmic membrane (CM) markers, including electron transfer and transport proteins, as well as general membrane protein assembly factors confirming the origin of the UPB from both peripheral respiratory membrane and sites of active CM invagination that give rise to the ICM. The changes in ICM vesicles were correlated to AFM mapping results (Adams and Hunter, Biochim Biophys Acta 1817:1616-1627, 2012), in which the increasing LH2 levels were shown to form densely packed LH2-only domains, representing the light-responsive antenna complement formed under low illumination. The advances described here could never have been envisioned when the author was first introduced in the mid-1960s to the intricacies of the photosynthetic apparatus during a lecture delivered in a graduate Biochemistry course at the University of Illinois by Govindjee, to whom this volume is dedicated on the occasion of his 80th birthday.

  18. Impact of heavy metals on hydrogen production from organic fraction of municipal solid waste using co-culture of Enterobacter aerogenes and E. Coli.

    PubMed

    Sharma, Preeti; Melkania, Uma

    2018-05-01

    In the present study, the effect of heavy metals (lead, mercury, copper, and chromium) on the hydrogen production from the organic fraction of municipal solid waste (OFMSW) was investigated using co-culture of facultative anaerobes Enterobacter aerogenes and E. coli. Heavy metals were applied at concentration range of 0.5, 1, 2, 5, 10, 20, 50 and 100 mg/L. The results revealed that lead, mercury, and chromium negatively affected hydrogen production for the range of concentrations applied. Application of copper slightly enhanced hydrogen production at low concentration and resulted in the hydrogen yield of 36.0 mLH 2 /gCarbo initial with 10 mg/L copper supplementation as compared to 24.2 mLH 2 /gCarbo initial in control. However, the higher concentration of copper (>10 mg/L) declined hydrogen production. Hydrogen production inhibition potential of heavy metals can be arranged in the following increasing order: Cu 2+  < Cr 6+  < Pb 2+  < Hg 2+ . COD removal rate and volatile fatty acid generation efficiencies were also significantly affected by heavy metal addition. Thus, the present study reveals that the presence of heavy metals in the feedstock is detrimental for the hydrogen production. Therefore, it is essential to remove the toxic heavy metals prior to anaerobic digestion. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Real-Time Dynamic Model Learning and Adaptation for Underwater Vehicles

    DTIC Science & Technology

    2013-09-01

    LHr f AS FS LHr f α α α α α α α α = − + − + − + − + (9) Note: For ease of notation s● = sin(●), c●=cos(●), and t●=tan(●). LV, LH1, and LH2 are...propellers of the aft or forward pair, and LH2 is defined as the distance between the centroid of the propellers of the right or left side pair

  20. The observation of ultrafast excited-state dynamical evolution in B800- partially or completely released LH2 of Rhodobacter sphaeroides 601 at room temperature.

    PubMed

    Liu, Weimin; Liu, Yuan; Yan, Yongli; Liu, Kangjun; Guo, Lijun; Xu, Chunhe; Qian, Shixiong

    2006-04-01

    Photodynamics of two kinds of peripheral antenna complexes (LH2 of Rhodobacter sphaeroides, native LH2 (RS601) and B800-released LH2 where B800-BChls were partially or completely removed with different pH treatments), were studied using femtosecond pump-probe technique at different laser wavelengths. The obtained results for these samples with different B800/B850 ratios demonstrated that under the excitation around B800 nm, the photoabsorption and photobleaching dynamics were caused by the direct excitation of upper excitonic levels of B850 and excited state of B800 pigments, respectively. Furthermore, the removal of B800 pigments had little effect on the energy transfer processes of B850 interband/intraband transfer.

  1. Gonadotrophin-releasing activity of neurohypophysial hormones: II. The pituitary oxytocin receptor mediating gonadotrophin release differs from that of corticotrophs.

    PubMed

    Evans, J J; Catt, K J

    1989-07-01

    Neurohypophysial hormones stimulate gonadotrophin release from dispersed rat anterior pituitary cells in vitro, acting through receptors distinct from those which mediate the secretory response to gonadotrophin-releasing hormone (GnRH). The LH response to oxytocin was not affected by the presence of the phosphodiesterase inhibitor, methyl isobutylxanthine, but was diminished in the absence of extracellular calcium and was progressively increased as the calcium concentration in the medium was raised to normal. In addition, the calcium channel antagonist, nifedipine, suppressed oxytocin-stimulated secretion of LH. It is likely that the mechanisms of LH release induced by GnRH and neurohypophysial hormones are similar, although stimulation of gonadotrophin secretion is mediated by separate receptor systems. Oxytocin was more active than vasopressin in releasing LH, but less active in releasing ACTH. The highly selective oxytocin agonist, [Thr4,Gly7]oxytocin, elicited concentration-dependent secretion of LH but had little effect on corticotrophin secretion. The neurohypophysial hormone antagonist analogues, [d(CH2)5Tyr(Me)2]vasopressin, [d(CH2)5Tyr(Me)2,Orn8]vasotocin and [d(CH2)5D-Tyr(Et)2Val4,Cit8]vasopressin, inhibited the LH response to both oxytocin and vasopressin. However, [d(CH2)5Tyr(Me)2]vasopressin was much less effective in inhibiting the ACTH response to the neurohypophysial hormones, and [d(CH2)5Tyr-(Me)2,Orn8]vasotocin and [d(CH2)5D-Tyr(Et)2,Val4,Cit8]vasopressin exhibited no inhibitory activity against ACTH release. Thus, agonist and antagonist analogues of neurohypophysial hormones display divergent activities with regard to LH and ACTH responses, and the neuropeptide receptor mediating gonadotroph activation is clearly different from that on the corticotroph. Whereas the corticotroph receptor is a vasopressin-type receptor an oxytocin-type receptor is responsible for gonadotrophin release by neurohypophysial hormones.

  2. High Specific Power Motors in LN2 and LH2

    NASA Technical Reports Server (NTRS)

    Brown, Gerald V.; Jansen, Ralph H.; Trudell, Jeffrey J.

    2007-01-01

    A switched reluctance motor has been operated in liquid nitrogen (LN2) with a power density as high as that reported for any motor or generator. The high performance stems from the low resistivity of Cu at LN2 temperature and from the geometry of the windings, the combination of which permits steady-state rms current density up to 7000 A/cm2, about 10 times that possible in coils cooled by natural convection at room temperature. The Joule heating in the coils is conducted to the end turns for rejection to the LN2 bath. Minimal heat rejection occurs in the motor slots, preserving that region for conductor. In the end turns, the conductor layers are spaced to form a heat-exchanger-like structure that permits nucleate boiling over a large surface area. Although tests were performed in LN2 for convenience, this motor was designed as a prototype for use with liquid hydrogen (LH2) as the coolant. End-cooled coils would perform even better in LH2 because of further increases in copper electrical and thermal conductivities. Thermal analyses comparing LN2 and LH2 cooling are presented verifying that end-cooled coils in LH2 could be either much longer or could operate at higher current density without thermal runaway than in LN2.

  3. Production of Antiserum to LH-Releasing Hormone (LH-RH) Associated with Gonadal Atrophy in Rabbits: Development of Radioimmunoassays for LH-RH

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    ARIMURA, A.; SATO, H.; KUMASAKA, T.

    1973-11-01

    Repeated injections of synthetic LH -- RH decapeptide, adsorbed on polyvinylpyrrolidone and emulsified with complete Freund's adjuvant, resulted in the production of a specific antiserum to LH-- RH in two of three rabbits. The animals that produced this antiserum showed a reduction of pituitary LH content and marked atrophy of the testes. The antiserum-antibody complex was detected by the complement flxation test. The antiserum was capable of binding /sup 125/I- labeled LH--RH. After iodination of LHRH (using /sup 125/I and either the chloramine T or lactoperoxidase method) separation of the iodination products on CMC yielded three main peaks of radioactivity:more » The first was free iodide, the second was labeled peptide with low immunoreactivity, and the third was immunoreactive peptide. This 3rd peak consisted of two or three subpeaks; the leading subpeak(s) were more readily bound by antiserum than the trailing one(s). Binding of these fractions to antiserum was increased in the presence of small amounts of unlabeled LH--RH (a phenomenon called paradoxical binding or hock effect) but inhibited by larger amounts. Both the augmentation and the inhibition effects were dose-related, allowing the development of two different radioimmunoassay (RIA) systems for LH--RH. An ordinary (coinpetitive) type of RIA was developed in which a small amount (0.31 ng/assay tube) of unlabeled LH-- RH was added to the labeled peptide. This saturated the antiserum's capacity for paradoxical binding, so that further addition of LH-- RH (from 0.04 to 2.5 ng/ tube) inhibited binding of labeled LH--RH. The assay developed using paradoxical binding omitted the premixing of labeled and unlabeled LH--RH; in this assay addition of very small amounts (0.5 to 310 pg) of unlabeled LH--RH to the assay tubes increased the amount of label bound to antiserum and allowed construction of a parabolic curve of positive slope when B/T was plotted against arithmetic dose. The assays seem to be highly specific for LH--RH although both polymers and degradation products of LH--RH appeared to have some immunoreactivity.« less

  4. DFT study of cyanide oxidation on surface of Ge-embedded carbon nanotube

    NASA Astrophysics Data System (ADS)

    Gao, Wei; Milad Abrishamifar, Seyyed; Ebrahimzadeh Rajaei, Gholamreza; Razavi, Razieh; Najafi, Meysam

    2018-03-01

    In recent years, the discovery of suitable catalyst to oxidation of the cyanide (CN) has high importance in the industry. In present study, in the first step, the carbon nanotube (CNT) with the Ge atom embedded and the surface of Ge-CNT via the O2 molecule activated. In second step, the oxidation of CN on surface of the Ge-CNT via the Langmuir Hinshelwood (LH) and the Eley Rideal (ER) mechanisms was investigated. Results show that O2-Ge-CNT oxidized the CN molecule via the Ge-CNT-O-O∗ + CN → Ge-CNT-O-O∗-CN → Ge-CNT-O∗ + OCN and the Ge-CNT-O∗ + CN → Ge-CNT + OCN reactions. Results show that oxidation of CN on surface of Ge-CNT via the LH mechanism has lower energy barrier than ER mechanism. Finally, calculated parameters reveal that Ge-CNT is acceptable catalyst with high performance for CN oxidation, form theoretical point of view.

  5. Multilayer-MCTDH approach to the energy transfer dynamics in the LH2 antenna complex

    NASA Astrophysics Data System (ADS)

    Shibl, Mohamed F.; Schulze, Jan; Al-Marri, Mohammed J.; Kühn, Oliver

    2017-09-01

    The multilayer multiconfiguration time-dependent Hartree method is used to study the coupled exciton-vibrational dynamics in a high-dimensional nonameric model of the LH2 antenna complex of purple bacteria. The exciton-vibrational coupling is parametrized within the Huang-Rhys model according to phonon and intramolecular vibrational modes derived from an experimental bacteriochlorophyll spectral density. In contrast to reduced density matrix approaches, the Schrödinger equation is solved explicitly, giving access to the full wave function. This facilitates an unbiased analysis in terms of the coupled dynamics of excitonic and vibrational degrees of freedom. For the present system, we identify spectator modes for the B800 to B800 transfer and we find a non-additive effect of phonon and intramolecular vibrational modes on the B800 to B850 exciton transfer.

  6. High Specific Power Motors in LN2 and LH2

    NASA Technical Reports Server (NTRS)

    Brown, Gerald V.; Jansen, Ralph H.; Trudell, Jeffrey J.

    2007-01-01

    A switched reluctance motor has been operated in liquid nitrogen (LN2) with a power density as high as that reported for any motor or generator. The high performance stems from the low resistivity of Cu at LN2 temperature and from the geometry of the windings, the combination of which permits steady-state rms current density up to 7000 A/sq cm, about 10 times that possible in coils cooled by natural convection at room temperature. The Joule heating in the coils is conducted to the end turns for rejection to the LN2 bath. Minimal heat rejection occurs in the motor slots, preserving that region for conductor. In the end turns, the conductor layers are spaced to form a heat-exchanger-like structure that permits nucleate boiling over a large surface area. Although tests were performed in LN2 for convenience, this motor was designed as a prototype for use with liquid hydrogen (LH2) as the coolant. End-cooled coils would perform even better in LH2 because of further increases in copper electrical and thermal conductivities. Thermal analyses comparing LN2 and LH2 cooling are presented verifying that end-cooled coils in LH2 could be either much longer or could operate at higher current density without thermal runaway than in LN2.

  7. Conformational Complexity in the LH2 Antenna of the Purple Sulfur Bacterium Allochromatium vinosum Revealed by Hole-Burning Spectroscopy.

    PubMed

    Kell, Adam; Jassas, Mahboobe; Acharya, Khem; Hacking, Kirsty; Cogdell, Richard J; Jankowiak, Ryszard

    2017-06-15

    This work discusses the protein conformational complexity of the B800-850 LH2 complexes from the purple sulfur bacterium Allochromatium vinosum, focusing on the spectral characteristics of the B850 chromophores. Low-temperature B850 absorption and the split B800 band shift blue and red, respectively, at elevated temperatures, revealing isosbestic points. The latter indicates the presence of two (unresolved) conformations of B850 bacteriochlorophylls (BChls), referred to as conformations 1 and 2, and two conformations of B800 BChls, denoted as B800 R and B800 B . The energy differences between average site energies of conformations 1 and 2, and B800 R and B800 B are similar (∼200 cm -1 ), suggesting weak and strong hydrogen bonds linking two major subpopulations of BChls and the protein scaffolding. Although conformations 1 and 2 of the B850 chromophores, and B800 R and B800 B , exist in the ground state, selective excitation leads to 1 → 2 and B800 R → B800 B phototransformations. Different static inhomogeneous broadening is revealed for the lowest energy exciton states of B850 (fwhm ∼195 cm -1 ) and B800 R (fwhm ∼140 cm -1 ). To describe the 5 K absorption spectrum and the above-mentioned conformations, we employ an exciton model with dichotomous protein conformation disorder. We show that both experimental data and the modeling study support a two-site model with strongly and weakly hydrogen-bonded B850 and B800 BChls, which under illumination undergo conformational changes, most likely caused by proton dynamics.

  8. Project Themis: PIV Measurement of Elbow Flow through a Flow Conditioner

    DTIC Science & Technology

    2011-12-01

    validation of the component. CFD simulations, using LH2 , showed that the pipe with a VORTAB generated more vorticity at the exit than the pipe without a...using LH2 , showed that the pipe with a Vortab generated more vorticity at the exit than the pipe without a Vortab. PA#11932 4 Particle Image...number Fluid Vortab location Comment 9,000,000 LH2 9D USET installation 32,000 Air 9D For Validation Additional details • Fluent • k-ε

  9. Anchored LH2 complexes in 2D polarization imaging.

    PubMed

    Tubasum, Sumera; Sakai, Shunsuke; Dewa, Takehisa; Sundström, Villy; Scheblykin, Ivan G; Nango, Mamoru; Pullerits, Tõnu

    2013-09-26

    Protein is a soft material with inherently large structural disorder. Consequently, the bulk spectroscopies of photosynthetic pigment protein complexes provide averaged information where many details are lost. Here we report spectroscopy of single light-harvesting complexes where fluorescence excitation and detection polarizations are both independently rotated. Two samples of peripheral antenna (LH2) complexes from Rhodopseudomonas acidophila were studied. In one, the complexes were embedded in polyvinyl alcohol (PVA) film; in the other, they were anchored on the glass surface and covered by the PVA film. LH2 contains two rings of pigment molecules-B800 and B850. The B800 excitation polarization properties of the two samples were found to be very similar, indicating that orientation statistics of LH2s are the same in these two very different preparations. At the same time, we found a significant difference in B850 emission polarization statistics. We conclude that the B850 band of the anchored sample is substantially more disordered. We argue that both B800 excitation and B850 emission polarization properties can be explained by the tilt of the anchored LH2s due to the spin-casting of the PVA film on top of the complexes and related shear forces. Due to the tilt, the orientation statistics of two samples become similar. Anchoring is expected to orient the LH2s so that B850 is closer to the substrate. Consequently, the tilt-related strain leads to larger deformation and disorder in B850 than in B800.

  10. Future orbital transfer vehicle technology study. Volume 2: Technical report

    NASA Technical Reports Server (NTRS)

    Davis, E. E.

    1982-01-01

    Missions for future orbit transfer vehicles (1995-2010) are identified and the technology, operations and vehicle concepts that satisfy the transportation requirements are defined. Comparison of reusable space and ground based LO2/LH2 OTV's was made. Both vehicles used advanced space engines and aero assist capability. The SB OTV provided advantages in life cycle cost, performance and potential for improvement. Comparison of an all LO2/LH2 OTV fleet with a fleet of LO2/LH2 OTVs and electric OTV's was also made. The normal growth technology electric OTV used silicon cells with heavy shielding and argon ion thrusters. This provided a 23% advantage in total transportation cost. The impact of accelerated technology was considered in terms of improvements in performance and cost effectiveness. The accelerated technology electric vehicle used GaAs cells and annealing but did not result in the mixed fleet being any cheaper than an all LO2/LH2 OTV fleet. It is concluded that reusable LO2/LH2 OTV's can serve all general purpose cargo roles between LEO and GEO for the forseeable future. The most significant technology for the second generation vehicle would be space debris protection, on-orbit propellant storage and transfer and on-orbit maintenance capability.

  11. NO—CO—O2 Reaction on a Metal Catalytic Surface using Eley—Rideal Mechanism

    NASA Astrophysics Data System (ADS)

    Waqar, Ahmad

    2008-10-01

    Interactions among the reacting species NO, CO and O2 on metal catalytic surfaces are studied by means of Monte Carlo simulation using the Eley-Rideal (ER) mechanism. The study of this three-component system is important for understanding of the reaction kinetics by varying the relative ratios of the reactants. It is found that contrary to the conventional Langmuir-Hinshelwood (LH) thermal mechanism in which two irreversible phase transitions are obtained between active states and poisoned states, a single phase transition is observed when the ER mechanism is combined with the LH mechanism. The phase diagrams of the surface coverage and the steady state production of CO2, N2 and N2 O are evaluated as a function of the partial pressures of the reactants in the gas phase. The continuous production of CO2 starts as soon as the CO pressure is switched on and the second order phase transition at the first critical point is eliminated, which is in agreement with the experimental findings.

  12. Distinct functions of neuromedin u and neuromedin s in orange-spotted grouper.

    PubMed

    Li, Shuisheng; Xiao, Ling; Liu, Qiongyu; Zheng, Binbin; Chen, Huapu; Liu, Xiaochun; Zhang, Yong; Lin, Haoran

    2015-10-01

    Neuromedin U (NMU) and neuromedin S (NMS) play inhibitory roles in the regulation of food intake and energy homeostasis in mammals. However, their functions are not clearly established in teleost fish. In the present study, nmu and nms homologs were identified in several fish species. Subsequently, their cDNA sequences were cloned from the orange-spotted grouper (Epinephelus coioides). Sequence analysis showed that the orange-spotted grouper Nmu proprotein contains a 21-amino acid mature Nmu peptide (Nmu-21). The Nms proprotein lost the typical mature Nms peptide, but it retains a putative 34-amino acid peptide (Nmsrp). In situ hybridization revealed that nmu- and nms-expressing cells are mainly localized in the hypothalamic regions associated with appetite regulation. Food deprivation decreased the hypothalamic nmu mRNA levels but induced an increase of nms mRNA levels. Periprandial expression analysis showed that hypothalamic expression of nmu increased significantly at 3 h post-feeding, while nms expression was elevated at the normal feeding time. I.p. injection of synthetic Nmu-21 peptide suppressed the hypothalamic neuropeptide y (npy) expression, while Nmsrp administration significantly increased the expression of npy and orexin in orange-spotted grouper. Furthermore, the mRNA levels of LH beta subunit (lhβ) and gh in the pituitary were significantly down-regulated after Nmu-21 peptide administration, while Nmsrp was able to significantly stimulate the expression of FSH beta subunit (fshβ), prolactin (prl), and somatolaction (sl). Our results indicate that nmu and nms possess distinct neuroendocrine functions and pituitary functions in the orange spotted grouper. © 2015 Society for Endocrinology.

  13. Development of Fe-based superconducting wires for liquid-hydrogen level sensors

    NASA Astrophysics Data System (ADS)

    Ishida, S.; Tsuchiya, Y.; Mawatari, Y.; Eisaki, H.; Nakano, A.; Yoshida, Y.

    2017-07-01

    We developed liquid-hydrogen (LH2) level sensors with Ba(Fe1-x Co x )2As2 superconducting wires (Co-Ba122 wires) as their detection elements. We fabricated Co-Ba122 wires with different Co concentrations x by using the powder-in-tube method. The superconducting transition temperatures of the wires were successfully controlled in the range of 20-25 K by changing x from 0.06 to 0.10. The resistance-temperature curves of the wires exhibited sharp superconducting transitions with widths of 0.5-1.0 K. In addition, we performed an operation test of the Co-Ba122 level sensors with LH2. Close correspondence between the output resistance and the actual LH2 level was observed for a sensor equipped with x = 0.09 wire, demonstrating that this sensor can accurately measure LH2 levels.

  14. Analysis of Poloidal Asymmetric Density Behaviors in SOL Induced by 4.6-GHz Lower Hybrid Launcher Power in EAST

    NASA Astrophysics Data System (ADS)

    Li, Y. C.; Ding, B. J.; Li, M. H.; Wang, M.; Liu, L.; Wang, X. J.; Xu, H. D.; Shan, J. F.; Liu, F. K.

    2018-02-01

    On the experimental advanced superconducting tokamak (EAST), a series of striations, including a few strong emissivity striations and several low emissivity striations, were observed in front of the 4.6-GHz lower hybrid (LH) launcher with the visible video camera for the LH power discharge. These striations indicate that LH may create significant poloidal scrape-off layer (SOL) density profile asymmetries in front of the LH launcher. These poloidal asymmetric density behaviors are further confirmed with the edge density measured by two Langmuir probes installed at the top and bottom of the LH launcher. The measured density depends on LH power injection and magnetic field direction. A 2D diffusive convective model was used to study the mechanisms of the observed striations and poloidal asymmetric density. The simulation results qualitatively match with the measured density, indicating these poloidal asymmetric effects are ascribed to the LHW-induced E LH × B t drift.

  15. Effects of recombinant gonadotropin hormones on the expression of vitellogenin, gonadotropin subunits and gonadotropin receptors in cinnamon clownfish, Amphiprion melanopus.

    PubMed

    Kim, Na Na; Habibi, Hamid R; Lee, Jehee; Choi, Cheol Young

    2012-08-01

    Gonadotropins (GTHs) are the key regulators of reproduction in vertebrates. The present study investigated autoregulatory effects of gonadotropins, using recombinant FSH (rFSH) and LH (rLH) in cinnamon clownfish (Amphiprion melanopus). Experiments were carried out to investigate the actions of cinnamon clownfish rFSH and rLH on expression of GTH subunits, GTH receptors, and vitellogenin (Vtg) mRNA in vivo and in vitro. Plasma estradiol-17β (E(2)) level was also measured in immature fish following treatments with rFSH and rLH. The results demonstrate increasing levels of GTH subunits, GTH-receptors, Vtg mRNA levels, as well as plasma E(2) levels following injection with rFSH and rLH. The findings support the hypothesis that LH and FSH stimulate reproduction, in part, by autoregulatory mechanisms leading to upregulation of GTH receptors and GTH hormone production in cinnamon clownfish. The results provide a framework for better understanding of the mechanisms of GTH-mediated control of reproduction in cinnamon clownfish and other vertebrates. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Carotenoid-bacteriochlorophyll energy transfer in LH2 complexes studied with 10-fs time resolution.

    PubMed

    Polli, Dario; Cerullo, Giulio; Lanzani, Guglielmo; De Silvestri, Sandro; Hashimoto, Hideki; Cogdell, Richard J

    2006-04-01

    In this report, we present a study of carotenoid-bacteriochlorophyll energy transfer processes in two peripheral light-harvesting complexes (known as LH2) from purple bacteria. We use transient absorption spectroscopy with approximately 10 fs temporal resolution, which is necessary to observe the very fast energy relaxation processes. By comparing excited-state dynamics of the carotenoids in organic solvents and inside the LH2 complexes, it has been possible to directly evaluate their energy transfer efficiency to the bacteriochlorophylls. In the case of okenone in the LH2 complex from Chromatium purpuratum, we obtained an energy transfer efficiency of etaET2=63+/-2.5% from the optically active excited state (S2) and etaET1=61+/-2% from the optically dark state (S1); for rhodopin glucoside contained in the LH2 complex from Rhodopseudomonas acidophila these values become etaET2=49.5+/-3.5% and etaET1=5.1+/-1%. The measurements also enabled us to observe vibrational energy relaxation in the carotenoids' S1 state and real-time collective vibrational coherence initiated by the ultrashort pump pulses. Our results are important for understanding the dynamics of early events of photosynthesis and relating it to the structural arrangement of the chromophores.

  17. Menstruation recovery after chemotherapy and luteinizing hormone-releasing hormone agonist plus tamoxifen therapy for premenopausal patients with breast cancer.

    PubMed

    Sakurai, Kenichi; Matsuo, Sadanori; Enomoto, Katsuhisa; Amano, Sadao; Shiono, Motomi

    2011-01-01

    Little is known about the period required for menstruation recovery after long-term luteinizing hormone-releasing hormone (LH-RH) agonist plus tamoxifen therapy following chemotherapy. In this study we investigated the period required for menstruation recovery after the therapy. The subjects comprised 105 premenopausal breast cancer patients who had undergone surgery. All patients were administered an LH-RH agonist for 24 months and tamoxifen for 5 years following the postoperative adjuvant chemotherapy, and the status of menstruation recovery was examined. Menstruation resumed in 16 cases (15.2%) after the last LH-RH agonist treatment session. The mean period from the last LH-RH agonist treatment to the recovery of menstruation was 6.9 months. The rate of menstruation recovery was 35.5% in patients aged 40 years or younger and 8.0% in those aged 41 years or older, and it was significantly higher in those aged 40 years or younger. The period until menstruation recovery tended to be longer in older patients at the end of treatment. This study showed that menstruation resumed after treatment at higher rates in younger patients. However, because it is highly likely that ovarian function will be destroyed by the treatment even in young patients, it is considered necessary to explain the risk to patients and obtain informed consent before introducing this treatment modality.

  18. Subtle spectral effects accompanying the assembly of bacteriochlorophylls into cyclic light harvesting complexes revealed by high-resolution fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Rätsep, Margus; Pajusalu, Mihkel; Linnanto, Juha Matti; Freiberg, Arvi

    2014-10-01

    We have observed that an assembly of the bacteriochloropyll a molecules into B850 and B875 groups of cyclic bacterial light-harvesting complexes LH2 and LH1, respectively, results an almost total loss of the intra-molecular vibronic structure in the fluorescence spectrum, and simultaneously, an essential enhancement of its phonon sideband due to electron-phonon coupling. While the suppression of the vibronic coupling in delocalized (excitonic) molecular systems is predictable, as also confirmed by our model calculations, a boost of the electron-phonon coupling is rather unexpected. The latter phenomenon is explained by exciton self-trapping, promoted by mixing the molecular exciton states with charge transfer states between the adjacent chromophores in the tightly packed B850 and B875 arrangements. Similar, although less dramatic trends were noted for the light-harvesting complexes containing chlorophyll pigments.

  19. Dephosphorylation and inactivation of NPR2 guanylyl cyclase in granulosa cells contributes to the LH-induced decrease in cGMP that causes resumption of meiosis in rat oocytes

    PubMed Central

    Egbert, Jeremy R.; Shuhaibar, Leia C.; Edmund, Aaron B.; Van Helden, Dusty A.; Robinson, Jerid W.; Uliasz, Tracy F.; Baena, Valentina; Geerts, Andreas; Wunder, Frank; Potter, Lincoln R.; Jaffe, Laurinda A.

    2014-01-01

    In mammals, the meiotic cell cycle of oocytes starts during embryogenesis and then pauses. Much later, in preparation for fertilization, oocytes within preovulatory follicles resume meiosis in response to luteinizing hormone (LH). Before LH stimulation, the arrest is maintained by diffusion of cyclic (c)GMP into the oocyte from the surrounding granulosa cells, where it is produced by the guanylyl cyclase natriuretic peptide receptor 2 (NPR2). LH rapidly reduces the production of cGMP, but how this occurs is unknown. Here, using rat follicles, we show that within 10 min, LH signaling causes dephosphorylation and inactivation of NPR2 through a process that requires the activity of phosphoprotein phosphatase (PPP)-family members. The rapid dephosphorylation of NPR2 is accompanied by a rapid phosphorylation of the cGMP phosphodiesterase PDE5, an enzyme whose activity is increased upon phosphorylation. Later, levels of the NPR2 agonist C-type natriuretic peptide decrease in the follicle, and these sequential events contribute to the decrease in cGMP that causes meiosis to resume in the oocyte. PMID:25183874

  20. LH/hCG-Receptor Expression May Have a Negative Prognostic Value in Low-Risk Endometrial Cancer.

    PubMed

    Noci, Ivo; Sorbi, Flavia; Mannini, Luca; Projetto, Elisabetta; Pillozzi, Serena; Ghizzoni, Viola; Lottini, Tiziano; Moncini, Daniela; Baroni, Gianna; Mungai, Francesco; Arcangeli, Annarosa; Fambrini, Massimiliano

    2016-01-01

    A 51 year-old woman was diagnosed with endometrial cancer (EC) and underwent surgical staging. Pathological evaluation showed a 2 cm × 1 cm G2 endometrioid EC with a 30% myometrial deep invasion (FIGO Stage 1A). The patient was classified as low risk of recurrence, and no adjuvant treatment was offered. Six months after surgery, the patient developed an early vescico-vaginal recurrence, and chemotherapy treatment was started. Few months later, a subsequent involvement of vaginal wall, ileum, and omentum was detected, and the patient underwent second surgery. LH/hCG-receptor (LH/hCG-R) expression has been previously reported to be associated with an invasive phenotype in EC cells. Moreover, in a preclinical mouse model of EC behaves as a prometastatic molecular device. We analyzed the expression level of LH/hCG-R in cancer specimens collected during surgeries. Molecular and immunohistochemical analyses showed a strong expression of both mRNA and protein for LH/hCG-R in all specimens. LH/hCG-R expression may be assessed together with other clinicopathological parameters in order to better predict the risk of recurrence in low-risk EC patients. Further clinical trials are warranted in order to validate LH/hCG-R as biomarker in EC.

  1. Vent System Analysis for the Cryogenic Propellant Storage Transfer Ground Test Article

    NASA Technical Reports Server (NTRS)

    Hedayat, A

    2013-01-01

    To test and validate key capabilities and technologies required for future exploration elements such as large cryogenic propulsion stages and propellant depots, NASA is leading the efforts to develop and design the Cryogenic Propellant Storage and Transfer (CPST) Cryogenic Fluid Management (CFM) payload. The primary objectives of CPST payload are to demonstrate: 1) in-space storage of cryogenic propellants for long duration applications; and 2) in-space transfer of cryogenic propellants. The Ground Test Article (GTA) is a technology development version of the CPST payload. The GTA consists of flight-sized and flight-like storage and transfer tanks, liquid acquisition devices, transfer, and pressurization systems with all of the CPST functionality. The GTA is designed to perform integrated passive and active thermal storage and transfer performance testing with liquid hydrogen (LH2) in a vacuum environment. The GTA storage tank is designed to store liquid hydrogen and the transfer tank is designed to be 5% of the storage tank volume. The LH2 transfer subsystem is designed to transfer propellant from one tank to the other utilizing pressure or a pump. The LH2 vent subsystem is designed to prevent over-pressurization of the storage and transfer tanks. An in-house general-purpose computer program was utilized to model and simulate the vent subsystem operation. The modeling, analysis, and the results will be presented in the final paper.

  2. Honey Attenuates the Detrimental Effects of Nicotine on Testicular Functions in Nicotine Treated Wistar Rats.

    PubMed

    Kolawole, T A; Oyeyemi, W A; Adigwe, C; Leko, B; Udeh, C; Dapper, D V

    2015-12-20

    Effect of honey on reproductive functions of male rats exposed to nicotine was examined in this study. Thirty-two adult male wistar rats (n=8/Group) were grouped as Control (distilled water), Nicotine (1.0mg/kg bwt), Honey (100mg/kg bwt) and Nicotine with Honey. The animals were orally treated for 35 days consecutively. Epididymis sperm motility, viability, morphology and counts were estimated, serum Follicle Stimulating Hormone (FSH), Leutinizing Hormone (LH) and Testosterone were assayed using ELISA method and testicular histology were also assessed. Significant reduction in percentage sperm motility, viability, morphology and counts were observed in nicotine group compared to control. Serum FSH, LH and testosterone levels were significantly reduced in nicotine group when compared with the control. There was significant improvement in sperm motility, viability, morphology, counts, FSH, LH and Testosterone in group co-treated with nicotine and honey  relative to nicotine group. Also, the degenerative seminiferous tubule architecture due to nicotine was improved by honey. In conclusion, honey may suppress nicotine toxic effect on reproductive functions in male Wistar rats.

  3. Reciprocal Cross Talk between Gonadotropin-Releasing Hormone (GnRH) and Prostaglandin Receptors Regulates GnRH Receptor Expression and Differential Gonadotropin Secretion

    PubMed Central

    Naor, Zvi; Jabbour, Henry N.; Naidich, Michal; Pawson, Adam J.; Morgan, Kevin; Battersby, Sharon; Millar, Michael R.; Brown, Pamela; Millar, Robert P.

    2007-01-01

    The asynchronous secretion of gonadotrope LH and FSH under the control of GnRH is crucial for ovarian cyclicity but the underlying mechanism is not fully resolved. Because prostaglandins (PG) are autocrine regulators in many tissues, we determined whether they have this role in gonadotropes. We first demonstrated that GnRH stimulates PG synthesis by induction of cyclooxygenase-2, via the protein kinase C/c-Src/phosphatidylinositol 3′-kinase/MAPK pathway in the LβT2 gonadotrope cell line. We then demonstrated that PGF2α and PGI2, but not PGE2 inhibited GnRH receptor expression by inhibition of phosphoinositide turnover. PGF2α, but not PGI2 or PGE2, reduced GnRH-induction of LHβ gene expression, but not the α-gonadotropin subunit or the FSHβ subunit genes. The prostanoid receptors EP1, EP2, FP, and IP were expressed in rat gonadotropes. Incubations of rat pituitaries with PGF2α, but not PGI2 or PGE2, inhibited GnRH-induced LH secretion, whereas the cyclooxygenase inhibitor, indomethacin, stimulated GnRH-induced LH secretion. None of these treatments had any effect on GnRH-induced FSH secretion. The findings have thus elaborated a novel GnRH signaling pathway mediated by PGF2α-FP and PGI2-IP, which acts through an autocrine/paracrine modality to limit autoregulation of the GnRH receptor and differentially inhibit LH and FSH release. These findings provide a mechanism for asynchronous LH and FSH secretions and suggest the use of combination therapies of GnRH and prostanoid analogs to treat infertility, diseases with unbalanced LH and FSH secretion and in hormone-dependent diseases such as prostatic cancer. PMID:17138645

  4. STS propellant densification feasibility study data book

    NASA Technical Reports Server (NTRS)

    Fazah, M. M.

    1994-01-01

    The feasibility of using densification or subcooling with respect to standard temperature propellants on the Space Transportation System (STS) in order to achieve a payload gain is discussed in this report. The objective is to determine the magnitude of the payload gain and to identify any system impacts to the space shuttle on either flight systems or ground systems. Results show that a payload benefit can be obtained by subcooling the liquid hydrogen (LH2) from a nominal temperature of 36.4 R to 28.5 R and by subcooling the liquid oxygen (LO2) from a nominal temperature of 164 R to either 132.1 R or 141.4 R. When the propellants are subcooled to 28.5 R and 132.1 R for the LH2 and LO2, respectively, a maximum payload gain of 7,324 lb can be achieved, and when the propellants are subcooled to 28.5 R and 141.5 R for the LH2 and LO2, respectively, a maximum payload gain of 6,841 lb can be achieved. If the LH2 is subcooled to 28.5 R while the LH2 and LO2 remains at the nominal conditions, a maximum payload gain of 1,303 lb can be achieved.

  5. Thermo-physical performance prediction of the KSC Ground Operation Demonstration Unit for liquid hydrogen

    NASA Astrophysics Data System (ADS)

    Baik, J. H.; Notardonato, W. U.; Karng, S. W.; Oh, I.

    2015-12-01

    NASA Kennedy Space Center (KSC) researchers have been working on enhanced and modernized cryogenic liquid propellant handling techniques to reduce life cycle costs of propellant management system for the unique KSC application. The KSC Ground Operation Demonstration Unit (GODU) for liquid hydrogen (LH2) plans to demonstrate integrated refrigeration, zero-loss flexible term storage of LH2, and densified hydrogen handling techniques. The Florida Solar Energy Center (FSEC) has partnered with the KSC researchers to develop thermal performance prediction model of the GODU for LH2. The model includes integrated refrigeration cooling performance, thermal losses in the tank and distribution lines, transient system characteristics during chilling and loading, and long term steady-state propellant storage. This paper will discuss recent experimental data of the GODU for LH2 system and modeling results.

  6. High efficiency light harvesting by carotenoids in the LH2 complex from photosynthetic bacteria: unique adaptation to growth under low-light conditions.

    PubMed

    Magdaong, Nikki M; LaFountain, Amy M; Greco, Jordan A; Gardiner, Alastair T; Carey, Anne-Marie; Cogdell, Richard J; Gibson, George N; Birge, Robert R; Frank, Harry A

    2014-09-25

    Rhodopin, rhodopinal, and their glucoside derivatives are carotenoids that accumulate in different amounts in the photosynthetic bacterium, Rhodoblastus (Rbl.) acidophilus strain 7050, depending on the intensity of the light under which the organism is grown. The different growth conditions also have a profound effect on the spectra of the bacteriochlorophyll (BChl) pigments that assemble in the major LH2 light-harvesting pigment-protein complex. Under high-light conditions the well-characterized B800-850 LH2 complex is formed and accumulates rhodopin and rhodopin glucoside as the primary carotenoids. Under low-light conditions, a variant LH2, denoted B800-820, is formed, and rhodopinal and rhodopinal glucoside are the most abundant carotenoids. The present investigation compares and contrasts the spectral properties and dynamics of the excited states of rhodopin and rhodopinal in solution. In addition, the systematic differences in pigment composition and structure of the chromophores in the LH2 complexes provide an opportunity to explore the effect of these factors on the rate and efficiency of carotenoid-to-BChl energy transfer. It is found that the enzymatic conversion of rhodopin to rhodopinal by Rbl. acidophilus 7050 grown under low-light conditions results in nearly 100% carotenoid-to-BChl energy transfer efficiency in the LH2 complex. This comparative analysis provides insight into how photosynthetic systems are able to adapt and survive under challenging environmental conditions.

  7. High Efficiency Light Harvesting by Carotenoids in the LH2 Complex from Photosynthetic Bacteria: Unique Adaptation to Growth under Low-Light Conditions

    PubMed Central

    2015-01-01

    Rhodopin, rhodopinal, and their glucoside derivatives are carotenoids that accumulate in different amounts in the photosynthetic bacterium, Rhodoblastus (Rbl.) acidophilus strain 7050, depending on the intensity of the light under which the organism is grown. The different growth conditions also have a profound effect on the spectra of the bacteriochlorophyll (BChl) pigments that assemble in the major LH2 light-harvesting pigment–protein complex. Under high-light conditions the well-characterized B800-850 LH2 complex is formed and accumulates rhodopin and rhodopin glucoside as the primary carotenoids. Under low-light conditions, a variant LH2, denoted B800-820, is formed, and rhodopinal and rhodopinal glucoside are the most abundant carotenoids. The present investigation compares and contrasts the spectral properties and dynamics of the excited states of rhodopin and rhodopinal in solution. In addition, the systematic differences in pigment composition and structure of the chromophores in the LH2 complexes provide an opportunity to explore the effect of these factors on the rate and efficiency of carotenoid-to-BChl energy transfer. It is found that the enzymatic conversion of rhodopin to rhodopinal by Rbl. acidophilus 7050 grown under low-light conditions results in nearly 100% carotenoid-to-BChl energy transfer efficiency in the LH2 complex. This comparative analysis provides insight into how photosynthetic systems are able to adapt and survive under challenging environmental conditions. PMID:25171303

  8. Clogging of Joule-Thomson Devices in Liquid Hydrogen Handling

    NASA Technical Reports Server (NTRS)

    Jurns, John M.; Lekki, John D.

    2009-01-01

    Experiments conducted at the NASA Glenn Research Center indicate that Joule-Thomson devices become clogged when transferring liquid hydrogen (LH2), operating at a temperature range from 20.5 to 24.4 K. Blockage does not exist under all test conditions but is found to be sensitive to the inlet temperature of the LH2. At a subcooled inlet temperature of 20.5 K blockage consistently appears but is dissipated when the fluid temperature is raised above 24.5 K. Clogging steadily reduced flow rate through the orifices, eventually resulting in complete blockage. This tendency poses a threat to spacecraft cryogenic propulsion systems that would utilize passive thermal control systems. We propose that this clogging is due to trace amounts of neon in the regular LH2 supply. Neon freezes at 24.5 K at one atmosphere pressure. It is postulated that between 20.5 and 24.5 K, neon remains in a meta-stable, supercooled liquid state. When impacting the face of an orifice, liquid neon droplets solidify and accumulate, blocking flow over time. The purpose of this test program was to definitively quantify the phenomena experimentally by obtaining direct visual evidence of orifice clogging by accretion from neon contaminates in the LH2 flow stream, utilizing state of the art imaging technology. Tests were conducted with LH2 flowing in the temperature range of 20.5 to 24.4 K. Additional imaging was also done at LH2 temperatures with no flow to verify clear view through the orifice.

  9. The kisspeptin-GnRH pathway in human reproductive health and disease

    PubMed Central

    Skorupskaite, Karolina; George, Jyothis T; Anderson, Richard A

    2014-01-01

    BACKGROUND The discovery of kisspeptin as key central regulator of GnRH secretion has led to a new level of understanding of the neuroendocrine regulation of human reproduction. The related discovery of the kisspeptin-neurokinin B-dynorphin (KNDy) pathway in the last decade has further strengthened our understanding of the modulation of GnRH secretion by endocrine, metabolic and environmental inputs. In this review, we summarize current understanding of the physiological roles of these novel neuropeptides, and discuss the clinical relevance of these discoveries and their potential translational applications. METHODS A systematic literature search was performed using PUBMED for all English language articles up to January 2014. In addition, the reference lists of all relevant original research articles and reviews were examined. This review focuses mainly on published human studies but also draws on relevant animal data. RESULTS Kisspeptin is a principal regulator of the secretion of gonadotrophins, and through this key role it is critical for the onset of puberty, the regulation of sex steroid-mediated feedback and the control of adult fertility. Although there is some sexual dimorphism, both neuroanatomically and functionally, these functions are apparent in both men and women. Kisspeptin acts upstream of GnRH and, following paracrine stimulatory and inhibitory inputs from neurokinin B and dynorphin (KNDy neuropeptides), signals directly to GnRH neurones to control pulsatile GnRH release. When administered to humans in different isoforms, routes and doses, kisspeptin robustly stimulates LH secretion and LH pulse frequency. Manipulation of the KNDy system is currently the focus of translational research with the possibility of future clinical application to regulate LH pulsatility, increasing gonadal sex steroid secretion in reproductive disorders characterized by decreased LH pulsatility, including hypothalamic amenorrhoea and hypogonadotropic hypogonadism. Conversely there may be scope to reduce the activity of the KNDy system to reduce LH secretion where hypersecretion of LH adds to the phenotype, such as in polycystic ovary syndrome. CONCLUSIONS Kisspeptin is a recently discovered neuromodulator that controls GnRH secretion mediating endocrine and metabolic inputs to the regulation of human reproduction. Manipulation of kisspeptin signalling has the potential for novel therapies in patients with pathologically low or high LH pulsatility. PMID:24615662

  10. The effects of Vitex agnus castus extract and its interaction with dopaminergic system on LH and testosterone in male mice.

    PubMed

    Nasri, Sima; Oryan, Shahrbano; Rohani, Ali Haeri; Amin, Gholam Reza

    2007-07-15

    The purpose of this study was to evaluate the probable effects of Vitex agnus castus (Vac.) on the male reproductive physiology. It is a well known fact that LH secretion from the anterior pituitary of mammals is controlled by many neurotransmiters such as dopamine. In this experiment, we have studied the effect of Vac. extract on the LH and testosterone hormones and its interaction with the dopaminergic system on male mice. In order to evaluate these effects, we used the hydroalcoholic Vac. extract (for extraction we used percolation technique) injection with the following doses: 65, 165, 265, 365 and 465 mg kg-', bromocriptine as a dopamine receptor agonist (5, 10, 20 mg kg(-1)) and haloperidol as a dopamine receptor antagonist (1, 1.5, 2, 2.5, 3 mg kg(-1)). To study the interaction between Vac. extract and dopaminergic system, we injected the optimum doses of Vac. with bromocriptine or haloperidol at the same time. Intraperitoneal injections were applied in all experiments, once a day for 30 days. The control group remained intact and the sham group received vehicle. After the last injection, we collected the animal blood serums for hormonal assays. LH and testosterone were measured by Radio Immuno Assay (RIA). LH and testosterone, showed significant decrease in bromocriptine group and haloperidol increased these hormones. Vac. extract decreased significantly the LH and testosterone levels. The coadministration of Vac. extract and bromocriptine decreased LH and testosterone. Coadministration of Vac. extract and haloperidol decreased LH and testosterone levels. These results suggest: dopamine regulates the gonadotroph-leydig cells axis. It appears that Vac. exertes effects through dopaminergic system and other pathways. The findings of this study show we can use Vac. extract for pathological cases of increasing LH and testosterone.

  11. Validation and Adjustment of the Leipzig-Halifax Acute Aortic Dissection Type A Scorecard.

    PubMed

    Mejàre-Berggren, Hanna; Olsson, Christian

    2017-11-01

    The novel Leipzig-Halifax (LH) scorecard for acute aortic dissection type A (AADA) stratifies risk of in-hospital death based on age, malperfusion syndromes, critical preoperative state, and coronary disease. The study aim was to externally validate the LH scorecard performance and, if adequate, propose adjustments. All consecutive AADA patients operated on from 1996 to 2016 (n = 509) were included to generate an external validation cohort. Variables related to in-hospital death were analyzed using univariable and multivariable analysis. The LH scorecard was applied to the validation cohort, compared with the original study, and variable selection was adjusted using validation measures for discrimination and calibration. In-hospital mortality rate was 17.7% (LH cohort 18.7%). Critical preoperative state and Penn class non-Aa were independent predictors (odds ratio [OR] 2.42 and 2.45, respectively) of in-hospital death. The LH scorecard was adjusted to include Penn class non-Aa, critical preoperative state, and coronary disease. Assessing discrimination, area under receiver operator characteristic curve for the LH scorecard was 0.61 versus 0.66 for the new scorecard (p = 0.086). In-hospital mortality rates in low-, medium-, and high-risk groups were 14%, 15%, and 48%, respectively (LH scorecard) versus 11%, 23%, and 43%, respectively (new scorecard), and goodness-of-fit p value was 0.01 versus 0.86, indicating better calibration by the new scorecard. A lower Akaike information criterion value, 464 versus 448, favored the new scorecard. Through adjustment of the LH scorecard after external validation, prognostic performance improved. Further validated, the LH scorecard could be a valuable risk prediction tool. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  12. Population pharmacokinetic/pharmacodynamic (PK/PD) modelling of the hypothalamic–pituitary–gonadal axis following treatment with GnRH analogues

    PubMed Central

    Tornøe, Christoffer W; Agersø, Henrik; Senderovitz, Thomas; Nielsen, Henrik A; Madsen, Henrik; Karlsson, Mats O; Jonsson, E Niclas

    2007-01-01

    Aims To develop a population pharmacokinetic/pharmacodynamic (PK/PD) model of the hypothalamic–pituitary–gonadal (HPG) axis describing the changes in luteinizing hormone (LH) and testosterone concentrations following treatment with the gonadotropin-releasing hormone (GnRH) agonist triptorelin and the GnRH receptor blocker degarelix. Methods Fifty-eight healthy subjects received single subcutaneous or intramuscular injections of 3.75 mg of triptorelin and 170 prostate cancer patients received multiple subcutaneous doses of degarelix of between 120 and 320 mg. All subjects were pooled for the population PK/PD data analysis. A systematic population PK/PD model-building framework using stochastic differential equations was applied to the data to identify nonlinear dynamic dependencies and to deconvolve the functional feedback interactions of the HPG axis. Results In our final PK/PD model of the HPG axis, the half-life of LH was estimated to be 1.3 h and that of testosterone 7.69 h, which corresponds well with literature values. The estimated potency of LH with respect to testosterone secretion was 5.18 IU l−1, with a maximal stimulation of 77.5 times basal testosterone production. The estimated maximal triptorelin stimulation of the basal LH pool release was 1330 times above basal concentrations, with a potency of 0.047 ng ml−1. The LH pool release was decreased by a maximum of 94.2% by degarelix with an estimated potency of 1.49 ng ml−1. Conclusions Our model of the HPG axis was able to account for the different dynamic responses observed after administration of both GnRH agonists and GnRH receptor blockers, suggesting that the model adequately characterizes the underlying physiology of the endocrine system. PMID:17096678

  13. Alternations in neuroendocrine and endocrine regulation of reproduction in male goldfish (Carassius auratus) following an acute and chronic exposure to vinclozolin, in vivo.

    PubMed

    Golshan, Mahdi; Hatef, Azadeh; Zare, Ava; Socha, Magdalena; Milla, Sylvain; Gosiewski, Grzegorz; Fontaine, Pascal; Sokołowska-Mikołajczyk, Mirosława; Habibi, Hamid R; Alavi, Sayyed Mohammad Hadi

    2014-10-01

    The fungicide vinclozolin (VZ) is in use globally and known to disrupt reproductive function in male. The present study tested the hypothesis that VZ disrupts testicular function in goldfish (Carassius auratus) by affecting brain-pituitary-testis axis. Goldfish were exposed to 100, 400 and 800 μg/L VZ and 5 μg/L 17β-estradiol (E2) for comparison. In VZ treated goldfish, 11-ketotesteosterone (11-KT) secretion was changed depending on dose and duration period of treatment. Following 7 days of exposure, 11-KT was decreased in goldfish exposed to 800 μg/L VZ, while it was increased in goldfish exposed to 100 μg/L VZ after 30 days of exposure. Circulating E2 level was unchanged in VZ treated goldfish, however the E2/11-KT ratio was increased in a concentration-related manner. In E2 treated goldfish, circulatory 11-KT and E2 levels were decreased and increased, respectively, which resulted in an increase in the E2/11-KT ratio. Exposure to VZ at 100 μg/L caused a significant increase in the circulatory luteinizing hormone (LH) after 30 days. In E2 treated fish circulatory LH was decreased, significantly. Transcripts of genes encoding gonadotropin-releasing hormone and androgen receptor in the brain, and those of genes encoding LH and follicle-stimulating hormone receptors, StAR, CYP17, and 3β-HSD in the testis changed in VZ-treated goldfish depending on concentration and period of treatment. mRNA of genes encoding vitellogenin and estrogen receptor in the liver and cytochrome P450 aromatase in the brain were increased in E2-treated goldfish. The results suggest that VZ-induced changes in 11-KT were due to disruption in brain-pituitary-testis axis and provide integrated characterization of VZ-related reproductive disorders in male fish. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. The influence of broiler activity, growth rate, and litter on carbon dioxide balances for the determination of ventilation flow rates in broiler production.

    PubMed

    Calvet, S; Estellés, F; Cambra-López, M; Torres, A G; Van den Weghe, H F A

    2011-11-01

    Carbon dioxide balances are useful in determining ventilation rates in livestock buildings. These balances need an accurate estimation of the CO(2) produced by animals and their litter to determine the ventilation flows. To estimate the daily variation in ventilation flow, it is necessary to precisely know the daily variation pattern of CO(2) production, which mainly depends on animal activity. The objective of this study was to explore the applicability of CO(2) balances for determining ventilation flows in broiler buildings. More specifically, this work aimed to quantify the amount of CO(2) produced by the litter, as well as the amount of CO(2) produced by the broilers, as a function of productive parameters, and to analyze the influence of broiler activity on CO(2) emissions. Gas concentrations and ventilation flows were simultaneously measured in 3 trials, with 1 under experimental conditions and the other 2 in a commercial broiler farm. In the experimental assay, broiler activity was also determined. At the end of the experimental trial, on the day after the removal of the broilers, the litter accounted for 20% of the total CO(2) produced, and the broilers produced 3.71 L/h of CO(2) per kg of metabolic weight. On the commercial farm, CO(2) production was the same for the 2 cycles (2.60 L/h per kg of metabolic weight, P > 0.05). However, substantial differences were found between CO(2) and broiler activity patterns after changes in light status. A regression model was used to explain these differences (R(2) = 0.52). Carbon dioxide increased with bird activity, being on average 3.02 L/h per kg of metabolic weight for inactive birds and 4.73 L/h per kg of metabolic weight when bird activity was highest. Overall, CO(2) balances are robust tools for determining the daily average ventilation flows in broiler farms. These balances could also be applied at more frequent intervals, but in this case, particular care is necessary after light status changes because of discrepancy between animal activity and CO(2) production.

  15. Increasing LH Pulsatility in Women With Hypothalamic Amenorrhoea Using Intravenous Infusion of Kisspeptin-54

    PubMed Central

    Jayasena, Channa N.; Abbara, Ali; Veldhuis, Johannes D.; Comninos, Alexander N.; Ratnasabapathy, Risheka; De Silva, Akila; Nijher, Gurjinder M. K.; Ganiyu-Dada, Zainab; Mehta, Amrish; Todd, Catriona; Ghatei, Mohammad A.; Bloom, Stephen R.

    2014-01-01

    Background: Hypothalamic amenorrhea (HA) is the one of the most common causes of period loss in women of reproductive age and is associated with deficient LH pulsatility. High-dose kisspeptin-54 acutely stimulates LH secretion in women with HA, but chronic administration causes desensitization. GnRH has paradoxical effects on reproductive activity; we therefore hypothesized that a dose-dependent therapeutic window exists within which kisspeptin treatment restores the GnRH/LH pulsatility in women with HA. Aim: The aim of the study was to determine whether constant iv infusion of kisspeptin-54 temporarily increases pulsatile LH secretion in women with HA. Methods: Five patients with HA each underwent six assessments of LH pulsatility. Single-blinded continuous iv infusion of vehicle or kisspeptin-54 (0.01, 0.03, 0.10, 0.30, or 1.00 nmol/kg/h) was administered. The LH pulses were detected using blinded deconvolution. Results: Kisspeptin increased LH pulsatility in all patients with HA, with peak responses observed at different doses in each patient. The mean peak number of pulses during infusion of kisspeptin-54 was 3-fold higher when compared with vehicle (number of LH pulses per 8 h: 1.6 ± 0.4, vehicle; 5.0 ± 0.5, kisspeptin-54, P < .01 vs vehicle). The mean peak LH pulse secretory mass during kisspeptin-54 was 6-fold higher when compared with vehicle (LH pulse secretory mass in international units per liter: 3.92 ± 2.31, vehicle; 23.44 ± 12.59, kisspeptin-54; P < .05 vs vehicle). Conclusions: Kisspeptin-54 infusion temporarily increases LH pulsatility in women with HA. Furthermore, we have determined the dose range within which kisspeptin-54 treatment increases basal and pulsatile LH secretion in women with HA. This work provides a basis for studying the potential of kisspeptin-based therapies to treat women with HA. PMID:24517142

  16. Protective effects of D-Trp6-luteinising hormone-releasing hormone microcapsules against cyclophosphamide-induced gonadotoxicity in female rats.

    PubMed

    Bokser, L; Szende, B; Schally, A V

    1990-06-01

    The possible protective effect of an agonist of luteinising hormone-releasing hormone (LH-RH) against the ovarian damage caused by cyclophosphamide was investigated in rats. D-Trp6-LH-RH microcapsules were injected once a month for 3 months, in a dose calculated to release 25 micrograms day-1. Control animals received the injection vehicle. Sixty days after the first injection of microcapsules, cyclophosphamide was given at a loading dose of 50 mg kg-1 followed by 5 mg kg-1 day-1 for 30 days, while the treatment with D-Trp6-LH-RH was continued. When the ovaries were examined 3 months and 5 months after discontinuation of treatment, a significant reduction in the total number of follicles (P less than 0.01) was found in non-pretreated animals given cyclophosphamide. This reduction affected mainly follicles larger than 100 microns. An irreversible disintegration and destruction of granulosa cells was also observed in this group. In animals pretreated with D-Trp6-LH-RH, administration of cyclophosphamide caused no reduction in the number and diameter of follicles. Thus, the treatment with D-Trp6-LH-RH microcapsules before and during chemotherapy prevented the ovarian injury inflicted by cyclophosphamide. The suppression of gonadal function by LH-RH analogues could be possibly utilised for the protection of the ovaries against damage caused by cytotoxic drugs.

  17. Development of LOX/LH2 tank system for H-I launch vehicle

    NASA Astrophysics Data System (ADS)

    Nozaki, Y.; Takamatsu, H.; Morino, Y.; Imagawa, K.

    Design features of the second stage of the prospective Japanese H-1 launch vehicle are described. The stage will use an LO2/LH2 fueled engine. The fuels will be contained in a 2219 Al alloy tank insulated with sprayed polyurethane foam. The total stage length will be 5.5 m, the volume 6.8 m, pressure 3.2 kg/sq cm (LOX) and 2.5 kg/sq cm (LH2). The diameter is 2.5 m and total fuel mass is 8.7 tons. Design verification tests, consisting of burning tests and thermal evaluation, are scheduled for the near future.

  18. Dephosphorylation of juxtamembrane serines and threonines of the NPR2 guanylyl cyclase is required for rapid resumption of oocyte meiosis in response to luteinizing hormone

    PubMed Central

    Shuhaibar, Leia C.; Egbert, Jeremy R.; Edmund, Aaron B.; Uliasz, Tracy F.; Dickey, Deborah M.; Yee, Siu-Pok; Potter, Lincoln R.; Jaffe, Laurinda A.

    2016-01-01

    The meiotic cell cycle of mammalian oocytes starts during embryogenesis and then pauses until luteinizing hormone (LH) acts on the granulosa cells of the follicle surrounding the oocyte to restart the cell cycle. An essential event in this process is a decrease in cyclic GMP in the granulosa cells, and part of the cGMP decrease results from dephosphorylation and inactivation of the natriuretic peptide receptor 2 (NPR2) guanylyl cyclase, also known as guanylyl cyclase B. However, it is unknown whether NPR2 dephosphorylation is essential for LH-induced meiotic resumption. Here, we prevented NPR2 dephosphorylation by generating a mouse line in which the seven regulatory serines and threonines of NPR2 were changed to the phosphomimetic amino acid glutamate (Npr2–7E). Npr2–7E/7E follicles failed to show a decrease in enzyme activity in response to LH, and the cGMP decrease was attenuated; correspondingly, LH-induced meiotic resumption was delayed. Meiotic resumption in response to EGF receptor activation was likewise delayed, indicating that NPR2 dephosphorylation is a component of the pathway by which EGF receptor activation mediates LH signaling. We also found that most of the NPR2 protein in the follicle was present in the mural granulosa cells. These findings indicate that NPR2 dephosphorylation in the mural granulosa cells is essential for the normal progression of meiosis in response to LH and EGF receptor activation. In addition, these studies provide the first demonstration that a change in phosphorylation of a transmembrane guanylyl cyclase regulates a physiological process, a mechanism that may also control other developmental events. PMID:26522847

  19. Hydrogen aircraft technology

    NASA Technical Reports Server (NTRS)

    Brewer, G. D.

    1991-01-01

    A comprehensive evaluation is conducted of the technology development status, economics, commercial feasibility, and infrastructural requirements of LH2-fueled aircraft, with additional consideration of hydrogen production, liquefaction, and cryostorage methods. Attention is given to the effects of LH2 fuel cryotank accommodation on the configurations of prospective commercial transports and military airlifters, SSTs, and HSTs, as well as to the use of the plentiful heatsink capacity of LH2 for innovative propulsion cycles' performance maximization. State-of-the-art materials and structural design principles for integral cryotank implementation are noted, as are airport requirements and safety and environmental considerations.

  20. Minocycline produced antidepressant-like effects on the learned helplessness rats with alterations in levels of monoamine in the amygdala and no changes in BDNF levels in the hippocampus at baseline.

    PubMed

    Arakawa, Shiho; Shirayama, Yukihiko; Fujita, Yuko; Ishima, Tamaki; Horio, Mao; Muneoka, Katsumasa; Iyo, Masaomi; Hashimoto, Kenji

    2012-01-01

    Previous studies have indicated that minocycline might function as an antidepressant drug. The aim of this study was to evaluate the antidepressant-like effects of minocycline, which is known to suppress activated microglia, using learned helplessness (LH) rats (an animal model of depression). Infusion of minocycline into the cerebral ventricle of LH rats induced antidepressant-like effects. However, infusion of minocycline into the cerebral ventricle of naïve rats did not produce locomotor activation in the open field tests, suggesting that the antidepressant-like effects of minocycline were not attributed to the enhanced locomotion. LH rats showed significantly higher serotonin turnover in the orbitofrontal cortex and lower levels of brain-derived neurotrophic factor (BDNF) in the hippocampus than control rats. However, these alterations in serotonin turnover and BDNF expression remained unchanged after treatment with minocycline. On the contrary, minocycline treatment of LH rats induced significant increases in the levels of dopamine and its metabolites in the amygdala when compared with untreated LH rats. Taken together, minocycline may be a therapeutic drug for the treatment of depression. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Neurokinin B receptor antagonism decreases luteinising hormone pulse frequency and amplitude and delays puberty onset in the female rat.

    PubMed

    Li, S Y; Li, X F; Hu, M H; Shao, B; Poston, L; Lightman, S L; O'Byrne, K T

    2014-08-01

    The neural mechanisms controlling puberty onset remain enigmatic. Humans with loss of function mutations in TAC3 or TACR3, the genes encoding neurokinin B (NKB) or its receptor, neurokinin-3 receptor (NK3R), respectively, present with severe congenital gonadotrophin deficiency and pubertal failure. Animal studies have shown ambiguous actions of NKB-NK3R signalling with respect to controlling puberty onset. The present study aimed to determine the role of endogenous NKB-NK3R signalling in the control of pulsatile luteinising hormone (LH) secretion and the timing of puberty onset, and also whether precocious pubertal onset as a result of an obesogenic diet is similarly regulated by this neuropeptide system. Prepubertal female rats, chronically implanted with i.c.v. cannulae, were administered SB222200, a NK3R antagonist, or artificial cerebrospinal fluid via an osmotic mini-pump for 14 days. SB222200 significantly delayed the onset of vaginal opening and first oestrus (as markers of puberty) compared to controls in both normal and high-fat diet fed animals. Additionally, serial blood sampling, via chronic indwelling cardiac catheters, revealed that the increase in LH pulse frequency was delayed and that the LH pulse amplitude was reduced in response to NK3R antagonism, regardless of dietary status. These data suggest that endogenous NKB-NK3R signalling plays a role in controlling the timing of puberty and the associated acceleration of gonadotrophin-releasing hormone pulse generator frequency in the female rat. © 2014 British Society for Neuroendocrinology.

  2. Differential Effects of Inescapable Stress on Locus Coeruleus GRK3, Alpha2-Adrenoceptor and CRF1 Receptor Levels in Learned Helpless and Non-Helpless Rats: A potential link to stress resilience

    PubMed Central

    Taneja, Manish; Salim, Samina; Saha, Kaustuv; Happe, H. Kevin; Qutna, Nidal; Petty, Frederick; Bylund, David B.; Eikenburg, Douglas C.

    2011-01-01

    Exposure of rats to unpredictable, inescapable stress results in two distinct behaviors during subsequent escape testing. One behavior, suggestive of lack of stress resilience, is prolonged escape latency compared to non-stressed rats and is labeled learned helplessness (LH). The other behavior suggestive of stress resilience is normal escape latency and is labeled non-helpless (NH). This study examines the effects of unpredictable, inescapable tail-shock stress (TSS) on alpha2-adrenoceptor (α2-AR) and corticotropin-releasing factor 1 receptor (CRF1) regulation as well as protein levels of G protein-coupled receptor kinase 3 (GRK3), GRK2, tyrosine hydroxylase (TH) plus carbonylated protein levels in locus coeruleus (LC), amygdala (AMG), cortex (COR) and striatum (STR). In NH rats, α2-AR and CRF1 receptors were significantly down-regulated in LC after TSS. No changes in these receptor levels were observed in the LC of LH rats. GRK3, which phosphorylates receptors and thereby contributes to α2-AR and CRF1 receptor down-regulation, was reduced in the LC of LH but not NH rats. GRK2 levels were unchanged. In AMG, GRK3 but not GRK2 levels were reduced in LH but not NH rats, and receptor regulation was impaired in LH rats. In STR, no changes in GRK3 or GRK2 levels were observed. Finally, protein carbonylation, an index of oxidative stress, was increased in the LC and AMG of LH but not NH rats. We suggest that reduced stress resilience after TSS may be related to oxidative stress, depletion of GRK3 and impaired regulation of α2-AR and CRF1 receptor in LC. PMID:21333691

  3. Estradiol and testosterone concentrations increase with fasting in weaned pups of the northern elephant seal (Mirounga angustirostris).

    PubMed

    Sherman-Cooney, R A; Ortiz, R M; Noren, D P; Pagarigan, L; Ortiz, C L; Talamantes, F

    2005-01-01

    Although neonatal development is generally associated with increased levels of circulating testosterone (T) and estradiol (E2), food deprivation may inhibit steroidogenesis. Therefore, these potentially conflicting stimuli were examined in fasting weaned northern elephant seal (Mirounga angustirostris) pups by measuring serum concentrations of T, E2, progesterone (P4), and luteinizing hormone (LH) by either radioimmunoassay (P4, LH) or enzymeimmunoassay (T, E2). Blood samples were obtained from 20 male and 20 female pups at both early (<1 wk postweaning) and late (6-8 wk postweaning) periods during their natural postweaning fast. T in males (early: 2.9 +/- 0.4 ng/mL; late: 16 +/- 2 ng/mL; P < 0.0001) and E2 in females (early: 42 +/- 6 pg/mL; late: 67 +/- 5 pg/mL; P < 0.01) increased between the two measurement periods, while P4 (early: 2.5 +/- 0.3 ng/mL; late: 2.1 +/- 0.3 ng/mL; P > 0.05) did not. LH increased (early: 46 +/- 4 pg/mL; late: 65 +/- 6 pg/mL; P < 0.05) in males but not in females (early: 69 +/- 9 pg/mL; late: 65 +/- 6 pg/mL; P > 0.05). Increases in LH and T suggest that LH may stimulate T secretion. Alternatively, relatively low concentrations of LH in both males and females may reflect negative feedback inhibition imposed by elevated T and E2 concentrations. Despite the inherent postweaning fast, concentrations of T and E2 increased, suggesting that they may be critical for the continued development of pups. Therefore, compensatory mechanisms may exist that alleviate the fasting-induced inhibition of gonadal steroidogenesis during neonatal development in elephant seal pups.

  4. Rainfall,bulk deposition of nutrients and their seasonal variation in two tropical lowland and montane forests in Borneo

    NASA Astrophysics Data System (ADS)

    Gomyo, M.; Kuraji, K.; Kitayama, K.; Suzuki, M.

    2008-12-01

    The Borneo Island, the third largest in the world, is experiencing rapid and extensive changes driven by population growth and economic expansion. This change has induced the tropical forest conversion to other land uses for subsistence cultivations, large-scale mono crop plantations and the irreversible loss of forest biodiversity. In this paper, we examine rainwater chemistry observed at two different national parks in Malaysian Borneo for 12 months. We present annual bulk nutrient input flux and its seasonality, and the results are compared with data obtained at a number of other locations in the tropics. The possible source of the atmospheric nutrients and factors determining the differences of the two sites in Borneo is discussed. Nutrient fluxes in rainfall were measured two times every week in natural tropical montane rain forest in Mount Kinabalu National Park (MK) and natural tropical lowland rain forest in Lambir Hills National Park (LH) in Malaysian Borneo. Annual rainfall in MK and LH were 3,232 and 2,978 mm yr-1 respectively. Three-month rainfall during the northeast monsoon season in LH was 1.6 times greater than that in MK, whereas the 3- month rainfall during the southwest monsoon season in MK was 2.8 times greater than that in LH. The difference of volume-weighed mean ion concentration of nutrients of rainwater between MK and LH is not significant except Mg and Ca. The correlation coefficient between Na and Cl concentration is greater in LH than in MK suggesting that the rainwater chemistry was affected by mainly marine origin in LH both marine and terrestrial origin in MK. From the comparison of annual flux of nutrients in MK and LH with the other sites in the other tropical sites, it was noted that the Na and Cl flux in LH, which is only 13.7 km from the coast, is relatively low compared with the other sites located less than 20 km from the coast. Classification of nutrients was done by cluster analysis of 3-month nutrient flux in MK and LH and the results support the hypothesis of the different origin of nutrients between MK an LH. The source of high Mg and SO4-S flux in LH might be the outcrops of bedrock along the roads which contains high Mg and SO4-S.

  5. Long-term subcutaneous pulsatile low dose LH-RH administration for treatment of infertile men with secondary hypogonadotrophic hypogonadism.

    PubMed

    Skarin, G; Nillius, S J; Wide, L

    1984-01-01

    Chronic pulsatile subcutaneous low dose LH-RH treatment was given to three infertile men with longstanding (2-4 years) secondary hypothalamic pituitary failure. Before the therapy they had very low serum concentrations of gonadotrophins and testosterone. They were impotent and could not produce any ejaculate for sperm analysis. The pulsatile LH-RH treatment, which was continued up to 250 days, was given by means of a small portable automatically-timed infusion pump. Fifty microliter of the LH-RH solution was infused during one min every 90 min. The LH-RH doses were 1, 5 and 20 micrograms. The serum concentrations of the gonadotrophins and testosterone were normalized in the three patients within 10 days of pulsatile low dose LH-RH therapy. Libido and potency returned. The first ejaculates contained no sperms. With continued LH-RH treatment spermatogenesis was induced and normalized. Two of the men fertilized their wives. The pregnancy tests were positive after 181 and 230 days of treatment, respectively. Two healthy girls have been born. Paternity tests were positive. The third man is still receiving pulsatile LH-RH therapy. He has up till now been treated for four months. Chronic pulsatile s.c. low dose LH-RH administration is a very promising new therapy for those hypogonadal men who previously have required human gonadotrophin treatment to restore fertility.

  6. Protostellar jets in the NIR: interaction with the ISM and correlation with the exciting source evolutionary phase

    NASA Astrophysics Data System (ADS)

    Caratti o Garatti, Alessio

    2006-03-01

    I present an in-depth near-IR (NIR) analysis of a sample of H2 jets from young embedded sources to compare the physical, kinematical properties and cooling mechanisms of the different flows. The sample comprises 23 outflows driven by Class 0 and I sources having low-intermediate solar luminosity (1-600 L(sun)). For such an analysis, I have utilized narrow band images centered on the H2 (2.12 micron) and [FeII] (1.64 micron) spectral lines, low resolution spectra (R~600) in the range 1-2.5 micron and high resolution spectra (R~10000) centered on H2 (2.12 micron) and [FeII] (1.64 micron) lines. At NIR wavelengths these two tracers (H2,[FeII]) are the main coolants of the gas, that is excited by strong radiative shocks. Narrow band images have been used to detect such shocked regions in both ionic and molecular components. [FeII] have been observed in ~74% of the outflows which in some cases indicate the presence of embedded Herbig Haro (HH) like objects. H2 line ratios have been used to estimate the visual extinction and the average temperature of the molecular gas. A(V) values range from ~2 to ~15 mag, while average temperatures range between ~2000 and ~4000 K. In several knots, however, a stratification of temperatures is found with maximum values up to 5000 K. Such a stratification is more commonly observed in those knots which also show [FeII] emission, while a thermalized gas at a single temperature is generally found in knots emitting only in molecular lines. Combining narrow band imaging with the parameters derived from the spectroscopic analysis, it was possible to measure the total luminosity of the H2 and [FeII] shocked regions (L(H2) and L([FeII])) in each flow. H2 is the major NIR coolant with an average L(H2)/L([FeII]) ratio of ~10^2. About 83% of the sources have a L(H2)/L(bol) ratio ~0.04, irrespective of the Class of the driving source, while a smaller group of sources (mostly Class I) have L(H2)/L(bol) an order of magnitude smaller. Such a separation reveals the non-homogeneous behaviour of Cl ass I, where sources with very different outflow activity can be found. These less luminous jets are originated by older sources, where L(bol) is not dominated anymore by the accretion luminosity. This is confirmed by a further analysis conducted on jets from six intermediate and high mass sources, four of them not included in the original sample. They have a faster evolution with respect to the low mass ones and thus only a fraction of their L(bol) is due to the accretion luminosity. For these objects I find a defined separation between the two Classes in the L(H2)-L(bol) plot. Viceversa, there is a straight correlation between L(H2) and L(acc) for all these sources. Finally, I compare the derived jet physical parameters to theoretical shock models. The observed H2 emission in the HH objects can be mostly reproduced by models of J-type shocks with magnetic precursors.

  7. Full color modulation of firefly luciferase through engineering with unified Stark effect.

    PubMed

    Cai, Duanjun; Marques, Miguel A L; Nogueira, Fernando

    2013-11-07

    The firefly luciferase has been a unique marking tool used in various bioimaging techniques. Extensive color modulation is strongly required to meet special marking demands; however, intentional and accurate wavelength tuning has yet to be achieved. Here, we demonstrate that the color shift of the firefly chromophore (OxyLH2-1) by internal and external fields can be described as a unified Stark shift. Electrostatic microenvironmental effects on fluorescent spectroscopy are modeled in vacuo through effective electric fields by using time-dependent density functional theory. A complete visible fluorescence spectrum of firefly chromophore is depicted, which enables one to control the emission in a specific color. As an application, the widely observed pH-correlated color shift is proved to be associated with the local Stark field generated by the trace water-ions (vicinal hydronium and hydroxide ions) at active sites close to the OxyLH2-1.

  8. Hemispheric differences in orthographic and semantic processing as revealed by event-related potentials

    PubMed Central

    Dickson, Danielle S.; Federmeier, Kara D.

    2015-01-01

    Differences in how the right and left hemispheres (RH, LH) apprehend visual words were examined using event-related potentials (ERPs) in a repetition paradigm with visual half-field (VF) presentation. In both hemispheres (RH/LVF, LH/RVF), initial presentation of items elicited similar and typical effects of orthographic neighborhood size, with larger N400s for orthographically regular items (words and pseudowords) than for irregular items (acronyms and meaningless illegal strings). However, hemispheric differences emerged on repetition effects. When items were repeated in the LH/RVF, orthographically regular items, relative to irregular items, elicited larger repetition effects on both the N250, a component reflecting processing at the level of visual form (orthography), and on the N400, which has been linked to semantic access. In contrast, in the RH/LVF, repetition effects were biased toward irregular items on the N250 and were similar in size across item types for the N400. The results suggest that processing in the LH is more strongly affected by wordform regularity than in the RH, either due to enhanced processing of familiar orthographic patterns or due to the fact that regular forms can be more readily mapped onto phonology. PMID:25278134

  9. Orthotopic transplantation of LH receptor knockout and wild-type ovaries.

    PubMed

    Chudgar, Daksha; Lei, Zhenmin; Rao, Ch V

    2005-10-07

    Luteinizing hormone (LH) receptor knockout animals have an ovarian failure due to an arrest in folliculogenesis at the antral stage. As a result, the animals have an infertility phenotype. The present study was undertaken to determine whether this phenotype could be reversed by orthotopic transplantation of wild-type ovaries. The results revealed that transplanting wild-type ovaries into null animals did not result in resumption of estrus cycles. Although the number of different types of follicles increased, none progressed to ovulation. The serum hormone profiles improved, reflecting the ovarian changes. The wild-type animals with null ovaries also failed to cycle and their ovaries and serum hormone levels were more like null animals with their own ovaries. Although the lack of rescue of null ovaries placed into wild-type animals was predicted, the failure of wild-type ovaries placed in null animals was not, which could be due to chronic exposure of transplanted tissue to high circulating LH levels and also possibly due to altered internal milieu in null animals. These findings may have implications for potential future considerations of grafting normal donor ovaries into women who have an ovarian failure resulting from inactivating LH receptor mutations.

  10. Chronic glue sniffing with transient central hypothyroidism and hypergonadotropism.

    PubMed

    Chen, Hua-Fen; Chen, Shwe-Winn; Chen, Peter; Su, Mei-Chin; See, Ting-Ting; Lee, Hsin-Yu

    2003-12-01

    Neuropsychiatric, gastrointestinal and muscular disorders associated with glue sniffing have been widely reported, but endocrinologic abnormalities of glue exposure are rarely mentioned in the literature. We report a 26-year old male patient, a chronic glue sniffer, who presented with weakness of both lower limbs. On physical examination, he had reduced muscle strength of his 4 limbs, especially in his lower limbs. Laboratory examination revealed hypokalemia with hyperchloremic metabolic acidosis. His thyroid function showed low TSH, T4, T3, free T4 and reverse T3 level. Other pituitary functions were normal apart from high FSH and LH level. TSH response to TRH stimulation was normal, but there was impaired T3 response to TRH. MRI of pituitary showed no significant changes. He continued glue sniffing after discharge. He repeatedly came to our hospital for recurrent hypokalemic paralysis. His serum T4 and free T4 level were low when he had certain amount of glue sniffing and it returned to normal after he stopped sniffing or sniffed less amount of glue. His serum T3 concentrations were normal most of the times thereafter. His FSH and LH level were persistently elevated, even after he did not sniff glue for 2 weeks. Low free T4, TSH and reverse T3 level associated with glue sniffing in our patient were compatible with central hypothyroidism. Toluene, a neurotoxic organic solvent, is present in glues. Being highly lipophilic, it can easily enter and is retained within the lipid-rich nervous system after being inhaled. Like other organic solvents, toluene has been shown to affect dopaminergic and adrenergic turnover within various parts of the brain. The effects on these neurotransmitters could lead to abnormal secretion of pituitary hormones resulting in transient central hypothyroidism and abnormal gonadotropin levels. Long-term harmful effect of central hypothyroidism and chronic influence of abnormal gonadotropins to reproduction function needs further observation.

  11. Evaluation of different ranges of LH:FSH ratios in polycystic ovarian syndrome (PCOS) - Clinical based case control study.

    PubMed

    Malini, N A; Roy George, K

    2018-05-01

    Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine and metabolic disorder among reproductive aged women, leading to infertility. One of the common clinical manifestations in PCOS is that there is a difference in the range of LH production in different case of PCOS and accordingly variability in LH:FSH ratio was observed. The aim of the present study was to evaluate different ranges of LH:FSH ratios in PCOS. In this cross sectional study, a consecutive series of 745 women (aged 28.11 ± 0.2) who were subjected to infertility treatment at specialist infertility clinics in central Travancore region were considered. About 50 healthy females (aged 27.58 ± 0.4) with regular menstrual cycles were regarded as control. The data were collected from hospital records using subject's written informed consent. PCOS patients were observed to have different ranges of LH:FSH ratios from < 1 range to 4.6-5.5 and subjects were classified into 7 PCO subgroups on the basis of their LH:FSH ratios. In whole PCO group, body weight, LH, FSH, LH:FSH ratio, insulin, HbA1c, estradiol, testosterone and TSH were significantly (P < .05) increased whereas progesterone and SHBG levels were significantly (P < .05) decreased in comparison to control. In various PCO subgroups as LH levels and LH:FSH ratios were increased, levels of insulin, testosterone and AMH were increased and SHBG levels were decreased accordingly. This finding suggested a dependence of insulin, LH and testosterone in initiating the hormonal imbalances in PCOS. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Lesions of the lateral hypothalamus impair pilocarpine-induced salivation in rats.

    PubMed

    Renzi, A; De Luca, L A; Menani, J V

    2002-09-15

    In the present study we investigated the effects of electrolytic lesions of the lateral hypothalamus (LH) in the salivation induced by intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) injection of the cholinergic agonist pilocarpine. Rats with sham or LH lesions and stainless steel cannulas implanted into the lateral ventricle (LV) were used. In rats anesthetized with urethane (1.25mg/kg of body weight) saliva was collected using pre-weighed cotton balls inserted in the animal mouth during a period of 7 min following i.c.v. or i.p. injection of pilocarpine. Injection of pilocarpine (1mg/kg of body weight) i.p. in sham-operated rats (6h, 2, 7, and 15 days after the surgery) induced salivation (497+/-24, 452+/-26, 476+/-30, and 560+/-75 mg/7 min, respectively). The effects of i.p. pilocarpine was reduced 6h, 2 and 7 days after LH lesions (162+/-37, 190+/-32, and 229+/-27 mg/7 min, respectively), not 15 days after LH lesions (416+/-89 mg/7 min). Injection of pilocarpine (120 micro g/micro l) i.c.v., in sham-operated rats (6h, 2, 7, and 15 days after the surgery) also produced salivation (473+/-20, 382+/-16, 396+/-14, and 427+/-47 mg/7 min, respectively). The salivation induced by i.c.v. pilocarpine was also reduced 6h, 2 and 7 days after LH lesions (243+/-19, 278+/-24, and 295+/-27 mg/7 min, respectively), not 15 days after LH lesions (385+/-48 mg/7 min). The present results show the participation of the LH in the salivation induced by central or peripheral injection of pilocarpine in rats, reinforcing the involvement of central mechanisms on pilocarpine-induced salivation.

  13. Laboratory hematology in the history of Clinical Chemistry and Laboratory Medicine.

    PubMed

    Hoffmann, Johannes J M L

    2013-01-01

    For the occasion of the 50th anniversary of the journal Clinical Chemistry and Laboratory Medicine (CCLM), an historic overview of papers that the journal has published in the field of laboratory hematology (LH) is presented. All past volumes of CCLM were screened for papers on LH and these were categorized. Bibliographic data of these papers were also analyzed. CCLM published in total 387 LH papers. The absolute number of LH papers published annually showed a significant increase over the years since 1985. Also the share of LH papers demonstrated a steady increase (overall mean 5%, but mean 8% over the past 4 years). The most frequent category was coagulation and fibrinolysis (23.5%). Authors from Germany contributed the most LH papers to the journal (22.7%), followed by the Netherlands and Italy (16.3 and 13.2%, respectively). Recent citation data indicated that other publications cited LH review papers much more frequently than other types of papers. The history of the journal reflects the emergence and development of laboratory hematology as a separate discipline of laboratory medicine.

  14. Fetal programming: excess prenatal testosterone reduces postnatal luteinizing hormone, but not follicle-stimulating hormone responsiveness, to estradiol negative feedback in the female.

    PubMed

    Sarma, Hirendra N; Manikkam, Mohan; Herkimer, Carol; Dell'Orco, James; Welch, Kathleen B; Foster, Douglas L; Padmanabhan, Vasantha

    2005-10-01

    Exposure of female sheep fetuses to excess testosterone (T) during early to midgestation produces postnatal hypergonadotropism manifest as a selective increase in LH. This hypergonadotropism may result from reduced sensitivity to estradiol (E2) negative feedback and/or increased pituitary sensitivity to GnRH. We tested the hypothesis that excess T before birth reduces responsiveness of LH and FSH to E2 negative feedback after birth. Pregnant ewes were treated with T propionate (100 mg/kg in cotton seed oil) or vehicle twice weekly from d 30-90 gestation. Responsiveness to E2 negative feedback was assessed at 12 and 24 wk of age in the ovary-intact female offspring. Our experimental strategy was first to arrest follicular growth and reduce endogenous E2 by administering the GnRH antagonist (GnRH-A), Nal-Glu (50 microg/kg sc every 12 h for 72 h), and then provide a fixed amount of exogenous E2 via an implant. Blood samples were obtained every 20 min at 12 wk and every 10 min at 24 wk before treatment, during and after GnRH-A treatment both before and after E2 implant. GnRH-A ablated LH pulsatility, reduced FSH by approximately 25%, and E2 production diminished to near detection limit of assay at both ages in both groups. Prenatal T treatment produced a precocious and selective reduction in responsiveness of LH but not FSH to E2 negative feedback, which was manifest mainly at the level of LH/GnRH pulse frequency. Collectively, these findings support the hypothesis that prenatal exposure to excess T decreases postnatal responsiveness to E2 inhibitory feedback of LH/GnRH secretion to contribute to the development of hypergonadotropism.

  15. PucC and LhaA direct efficient assembly of the light‐harvesting complexes in Rhodobacter sphaeroides

    PubMed Central

    Mothersole, David J.; Jackson, Philip J.; Vasilev, Cvetelin; Tucker, Jaimey D.; Brindley, Amanda A.; Dickman, Mark J.

    2015-01-01

    Summary The mature architecture of the photosynthetic membrane of the purple phototroph R hodobacter sphaeroides has been characterised to a level where an atomic‐level membrane model is available, but the roles of the putative assembly proteins LhaA and PucC in establishing this architecture are unknown. Here we investigate the assembly of light‐harvesting LH2 and reaction centre‐light‐harvesting1‐PufX (RC‐LH1‐PufX) photosystem complexes using spectroscopy, pull‐downs, native gel electrophoresis, quantitative mass spectrometry and fluorescence lifetime microscopy to characterise a series of lha A and puc C mutants. LhaA and PucC are important for specific assembly of LH1 or LH2 complexes, respectively, but they are not essential; the few LH1 subunits found in Δlha A mutants assemble to form normal RC‐LH1‐PufX core complexes showing that, once initiated, LH1 assembly round the RC is cooperative and proceeds to completion. LhaA and PucC form oligomers at sites of initiation of membrane invagination; LhaA associates with RCs, bacteriochlorophyll synthase (BchG), the protein translocase subunit YajC and the YidC membrane protein insertase. These associations within membrane nanodomains likely maximise interactions between pigments newly arriving from BchG and nascent proteins within the SecYEG‐SecDF‐YajC‐YidC assembly machinery, thereby co‐ordinating pigment delivery, the co‐translational insertion of LH polypeptides and their folding and assembly to form photosynthetic complexes. PMID:26419219

  16. Structure of the dimeric PufX-containing core complex of Rhodobacter blasticus by in situ atomic force microscopy.

    PubMed

    Scheuring, Simon; Busselez, Johan; Lévy, Daniel

    2005-01-14

    We have studied photosynthetic membranes of wild type Rhodobacter blasticus, a closely related strain to the well studied Rhodobacter sphaeroides, using atomic force microscopy. High-resolution atomic force microscopy topographs of both cytoplasmic and periplasmic surfaces of LH2 and RC-LH1-PufX (RC, reaction center) complexes were acquired in situ. The LH2 is a nonameric ring inserted into the membrane with the 9-fold axis perpendicular to the plane. The core complex is an S-shaped dimer composed of two RCs, each encircled by 13 LH1 alpha/beta-heterodimers, and two PufXs. The LH1 assembly is an open ellipse with a topography-free gap of approximately 25 A. The two PufXs, one of each core, are located at the dimer center. Based on our data, we propose a model of the core complex, which provides explanation for the PufX-induced dimerization of the Rhodobacter core complex. The QB site is located facing a approximately 25-A wide gap within LH1, explaining the PufX-favored quinone passage in and out of the core complex.

  17. In vivo intra-luteal implants of prostaglandin (PG) E(1) or E(2) (PGE(1), PGE(2)) prevent luteolysis in cows. I. Luteal weight, circulating progesterone, mRNA for luteal luteinizing hormone (LH) receptor, and occupied and unoccupied luteal receptors for LH.

    PubMed

    Weems, Yoshie S; Arreguin-Arevalo, J Alejandro; Nett, Torrance M; Vann, Rhonda C; Ford, Stephen P; Bridges, Phillip J; Welsh, Thomas H; Lewis, Andrew W; Neuendorff, Don A; Randel, Ronald D; Weems, Charles W

    2011-08-01

    Previously, it was reported that chronic intra-uterine infusion of PGE(1) or PGE(2) every four hours inhibited luteolysis in ewes. However, estradiol-17β or PGE(2) given intra-uterine every 8h did not inhibit luteolysis in heifers, but infusion of estradiol+PGE(2) inhibited luteolysis in heifers. The objective of this experiment was to determine whether and how intra-luteal implants containing PGE(1) or PGE(2) prevent luteolysis in Angus or Brahman cows. On day-13 post-estrus, Angus cows received no intra-luteal implant and corpora lutea were retrieved or Angus and Brahman cows received intra-luteal silastic implants containing Vehicle, PGE(1), or PGE(2) and corpora lutea were retrieved on day-19. Coccygeal blood was collected daily for analysis for progesterone. Breed did not influence the effect of PGE(1) or PGE(2) on luteal mRNA for LH receptors or unoccupied or occupied luteal LH receptors did not differ (P>0.05) so the data were pooled. Luteal weights of Vehicle-treated Angus or Brahman cows from days-13-19 were lower (P<0.05) than those treated with intra-luteal implants containing PGE(1) or PGE(2). Day-13 Angus luteal weights were heavier (P<0.05) than Vehicle-treated Angus cows on day-19 and luteal weights of day-13 corpora lutea were similar (P>0.05) to Angus cows on day-19 treated with intra-luteal implants containing PGE(1) or PGE(2). Profiles of circulating progesterone in Angus or Brahman cows treated with intra-luteal implants containing PGE(1) or PGE(2) differed (P<0.05) from controls, but profiles of progesterone did not differ (P>0.05) between breeds or between cows treated with intra-luteal implants containing PGE(1) or PGE(2). Intra-luteal implants containing PGE(1) or PGE(2) prevented (P<0.05) loss of luteal mRNA for LH receptors and unoccupied or occupied receptors for LH compared to controls. It is concluded that PGE(1) or PGE(2) alone delays luteolysis regardless of breed. We also conclude that either PGE(1) or PGE(2) prevented luteolysis in cows by up-regulating expression of mRNA for LH receptors and by preventing loss of unoccupied and occupied LH receptors in luteal tissue. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Risk Assessment and Scaling for the SLS LH2 ET

    NASA Technical Reports Server (NTRS)

    Hafiychuk, Halyna; Ponizovskaya-Devine, Ekaterina; Luchinsky, Dmitry; Khasin, Michael; Osipov, Viatcheslav V.; Smelyanskiy, Vadim N.

    2012-01-01

    In this report the main physics processes in LH2 tank during prepress and rocket flight are studied. The goal of this investigation is to analyze possible hazards and to make risk assessment in proposed LH2 tank designs for SLS with 5 engines (the situation with 4 engines is less critical). For analysis we use the multinode model (MNM) developed by us and presented in a separate report and also 3D ANSYS simulations. We carry out simulation and theoretical analysis the physics processes such as (i) accumulation of bubbles in LH2 during replenish stage and their collapsing in the liquid during the prepress; (ii) condensation-evaporation at the liquid-vapor interface and tank wall, (iv) heating the liquid near the interface and wall due to condensation and environment heat, (v) injection of hot He during prepress and of hot GH2 during flight, (vi) mixing and cooling of the injected gases due to heat transfer between the gases, liquid and the tank wall. We analyze the effects of these physical processes on the thermo- and fluid gas dynamics in the ullage and on the stratification of temperature in the liquid and assess the associated hazards. A special emphasize is put on the scaling predictions for the larger SLS LH2 tank.

  19. Response of prepubertal ewes primed with monensin or progesterone to administration of FSH.

    PubMed

    Sumbung, F P; Williamson, P; Carson, R S

    1987-11-01

    Prepubertal ewe lambs were treated with FSH after progesterone priming for 12 days (Group P), monensin supplementation for 14 days (Group M) or a standard diet (Group C). Serial blood samples were taken for LH and progesterone assay, and ovariectomy was performed on half of each group 38-52 h after start of treatment to assess ovarian function, follicular steroid production in vitro and the concentration of gonadotrophin binding sites in follicles. The remaining ewe lambs were ovariectomized 8 days after FSH treatment to determine whether functional corpora lutea were present. FSH treatment was followed by a preovulatory LH surge which occurred significantly later (P less than 0.05) and was better synchronized in ewes in Groups P and M than in those in Group C. At 13-15 h after the LH surge significantly more large follicles were present on ovaries from Group P and M ewes than in Group C. Follicles greater than 5 mm diameter from ewes in Groups P and M produced significantly less oestrogen and testosterone and more dihydrotestosterone, and had significantly more hCG binding sites, than did similar-sized follicles from Group C animals. Ovariectomy on Day 8 after the completion of FSH treatment showed that ewes in Groups P and M had significantly greater numbers of functional corpora lutea. These results indicate that, in prepubertal ewes, progesterone priming and monensin supplementation may delay the preovulatory LH surge, allowing follicles developing after FSH treatment more time to mature before ovulation. This may result in better luteinization of ruptured follicles in these ewes, with the formation of functional corpora lutea.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Fixation of carbon dioxide by macrocyclic lanthanide(III) complexes under neutral conditions producing self-assembled trimeric carbonato-bridged compounds with μ3-η2:η2:η2 bonding.

    PubMed

    Bag, Pradip; Dutta, Supriya; Biswas, Papu; Maji, Swarup Kumar; Flörke, Ulrich; Nag, Kamalaksha

    2012-03-28

    A series of mononuclear lanthanide(III) complexes [Ln(LH(2))(H(2)O)(3)Cl](ClO(4))(2) (Ln = La, Nd, Sm, Eu, Gd, Tb, Lu) of the tetraiminodiphenolate macrocyclic ligand (LH(2)) in 95 : 5 (v/v) methanol-water solution fix atmospheric carbon dioxide to produce the carbonato-bridged trinuclear complexes [{Ln(LH(2))(H(2)O)Cl}(3)(μ(3)-CO(3))](ClO(4))(4)·nH(2)O. Under similar conditions, the mononuclear Y(III) complex forms the dimeric compound [{Y(LH(2))(H(2)O)Cl}(μ(2)-CO(3)){Y(LH(2))(H(2)O)(2)}](ClO(4))(3)·4H(2)O. These complexes have been characterized by their IR and NMR ((1)H, (13)C) spectra. The X-ray crystal structures have been determined for the trinuclear carbonato-bridged compounds of Nd(III), Gd(III) and Tb(III) and the dinuclear compound of Y(III). In all cases, each of the metal centers are 8-coordinate involving two imine nitrogens and two phenolate oxygens of the macrocyclic ligand (LH(2)) whose two other imines are protonated and intramolecularly hydrogen-bonded with the phenolate oxygens. The oxygen atoms of the carbonate anion in the trinuclear complexes are bonded to the metal ions in tris-bidentate μ(3)-η(2):η(2):η(2) fashion, while they are in bis-bidentate μ(2)-η(2):η(2) mode in the Y(III) complex. The magnetic properties of the Gd(III) complex have been studied over the temperature range 2 to 300 K and the magnetic susceptibility data indicate a very weak antiferromagnetic exchange interaction (J = -0.042 cm(-1)) between the Gd(III) centers (S = 7/2) in the metal triangle through the carbonate bridge. The luminescence spectral behaviors of the complexes of Sm(III), Eu(III), and Tb(III) have been studied. The ligand LH(2) acts as a sensitizer for the metal ions in an acetonitrile-toluene glassy matrix (at 77 K) and luminescence intensities of the complexes decrease in the order Eu(3+) > Sm(3+) > Tb(3+).

  1. Atomistic non-adiabatic dynamics of the LH2 complex with a GPU-accelerated ab initio exciton model.

    PubMed

    Sisto, Aaron; Stross, Clem; van der Kamp, Marc W; O'Connor, Michael; McIntosh-Smith, Simon; Johnson, Graham T; Hohenstein, Edward G; Manby, Fred R; Glowacki, David R; Martinez, Todd J

    2017-06-14

    We recently outlined an efficient multi-tiered parallel ab initio excitonic framework that utilizes time dependent density functional theory (TDDFT) to calculate ground and excited state energies and gradients of large supramolecular complexes in atomistic detail - enabling us to undertake non-adiabatic simulations which explicitly account for the coupled anharmonic vibrational motion of all the constituent atoms in a supramolecular system. Here we apply that framework to the 27 coupled bacterio-chlorophyll-a chromophores which make up the LH2 complex, using it to compute an on-the-fly nonadiabatic surface-hopping (SH) trajectory of electronically excited LH2. Part one of this article is focussed on calibrating our ab initio exciton Hamiltonian using two key parameters: a shift δ, which corrects for the error in TDDFT vertical excitation energies; and an effective dielectric constant ε, which describes the average screening of the transition-dipole coupling between chromophores. Using snapshots obtained from equilibrium molecular dynamics simulations (MD) of LH2, we tune the values of both δ and ε through fitting to the thermally broadened experimental absorption spectrum, giving a linear absorption spectrum that agrees reasonably well with experiment. In part two of this article, we construct a time-resolved picture of the coupled vibrational and excitation energy transfer (EET) dynamics in the sub-picosecond regime following photo-excitation. Assuming Franck-Condon excitation of a narrow eigenstate band centred at 800 nm, we use surface hopping to follow a single nonadiabatic dynamics trajectory within the full eigenstate manifold. Consistent with experimental data, this trajectory gives timescales for B800→B850 population transfer (τ B800→B850 ) between 650-1050 fs, and B800 population decay (τ 800→ ) between 10-50 fs. The dynamical picture that emerges is one of rapidly fluctuating LH2 eigenstates that are delocalized over multiple chromophores and undergo frequent crossing on a femtosecond timescale as a result of the atomic vibrations of the constituent chromophores. The eigenstate fluctuations arise from disorder that is driven by vibrational dynamics with multiple characteristic timescales. The scalability of our ab initio excitonic computational framework across massively parallel architectures opens up the possibility of addressing a wide range of questions, including how specific dynamical motions impact both the pathways and efficiency of electronic energy-transfer within large supramolecular systems.

  2. In utero and childhood DDT, DDE, PBDE and PCBs exposure and sex hormones in adolescent boys: The CHAMACOS study.

    PubMed

    Eskenazi, Brenda; Rauch, Stephen A; Tenerelli, Rachel; Huen, Karen; Holland, Nina T; Lustig, Robert H; Kogut, Katherine; Bradman, Asa; Sjödin, Andreas; Harley, Kim G

    2017-04-01

    Dichlorodiphenyltrichloroethane (DDT), polybrominated diphenyl ether (PBDE) flame retardants, and polychlorinated biphenyls (PCBs) are believed to be endocrine-disrupting chemicals (EDCs) in humans and animals. The purpose of this study is to examine the relationship of in utero and childhood exposure to these purported EDCs and reproductive hormones in adolescent boys who participated in CHAMACOS, an ongoing birth cohort in California's Salinas Valley. We measured o,p'- and p,p'-DDT, p,p'-DDE, PBDEs and PCBs in serum collected from mothers during pregnancy or at delivery and from their sons at 9 years. We measured concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and total testosterone (T) from 234 of their sons at 12 years. In adjusted models, we found that a 10-fold increase in maternal prenatal serum concentrations of BDE-153 was associated with a 22.2% increase (95% CI: 1.0, 47.9) in FSH, a 96.6% increase (95% CI: 35.7, 184.7) in LH, and a 92.4% increase (95% CI: 20.9, 206.2) increase in T. Similarly, BDE-100 concentrations were associated with increases in boys' LH levels. A 10-fold increase in total prenatal ΣPCBs was associated with a 64.5% increase (95% CI: 8.6, 149.0) in FSH, primarily driven by non- dioxin-like congeners. Boys' hormone levels were only marginally associated with prenatal DDT or DDE in primary models, but when boys' Tanner stage at age 12 was added to models, prenatal maternal DDT levels were associated with decreases in LH (adjusted percent change per 10-fold increase=-18.5%, 95% CI: -29.8, -5.4) and T (percent change=-18.2%, 95% CI: -30.2, -4.2) and DDE with LH (percent change=-18.3%, 95% CI: -32.9, -0.6). Exposures measured in the children's serum at 9 years also showed associations between BDE-153 and ΣPCBs. However, there is evidence that these associations appear to be mediated by child BMI. This study suggests associations on male hormones of 12year old boys related to exposure to certain EDC exposure prenatally. The implications on future reproductive function in puberty and adulthood should be determined. Copyright © 2016 Elsevier GmbH. All rights reserved.

  3. In utero and childhood DDT, DDE, PBDE and PCBs exposure and sex hormones in adolescent boys: The CHAMACOS study

    PubMed Central

    Eskenazi, Brenda; Rauch, Stephen A.; Tenerelli, Rachel; Huen, Karen; Holland, Nina T.; Lustig, Robert H.; Kogut, Katherine; Bradman, Asa; Sjodin, Andreas; Harley, Kim G.

    2016-01-01

    Dichlorodiphenyltrichloroethane (DDT), polybrominated diphenyl ether (PBDE) flame retardants, and polychlorinated biphenyls (PCBs) are believed to be endocrine-disrupting chemicals (EDCs) in humans and animals. The purpose of this study is to examine the relationship of in utero and childhood exposure to these purported EDCs and reproductive hormones in adolescent boys who participated in CHAMACOS, an ongoing birth cohort in California’s Salinas Valley. We measured o,p′- and p,p′-DDT, p,p′- DDE, PBDEs and PCBs in serum collected from mothers during pregnancy or at delivery and from their sons at 9 years. We measured concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and total testosterone (T) from 234 of their sons at 12 years. In adjusted models, we found that a 10-fold increase in maternal prenatal serum concentrations of BDE-153 was associated with a 22.2% increase (95% CI: 1.0, 47.9) in FSH, a 96.6% increase (95% CI: 35.7, 184.7) in LH, and a 92.4% increase (95% CI: 20.9, 206.2) increase in T. Similarly, BDE-100 concentrations were associated with increases in boys’ LH levels. A 10-fold increase in total prenatal ΣPCBs was associated with a 64.5% increase (95% CI: 8.6, 149.0) in FSH, primarily driven by non-dioxin-like congeners. Boys’ hormone levels were only marginally associated with prenatal DDT or DDE in primary models, but when boys’ Tanner stage at age 12 was added to models, prenatal maternal DDT levels were associated with decreases in LH (adjusted percent change per 10-fold increase = −18.5%, 95% CI: −29.8, −5.4) and T (percent change = −18.2%, 95% CI: −30.2, −4.2) and DDE with LH (percent change = −18.3%, 95% CI: −32.9, −0.6). Exposures measured in the children’s serum at 9 years also showed associations between BDE-153 and ΣPCBs. However, there is evidence that these associations appear to be mediated by child BMI. This study suggests associations on male hormones of 12 year old boys related to exposure to certain EDC exposure prenatally. The implications on future reproductive function in puberty and adulthood should be determined. PMID:27876543

  4. [Revelation of a polymicrocystic ovary syndrome after one month's treatment by pulsatile GnRH in a patient presenting with functional hypothalamic amenorrhea].

    PubMed

    Reyss, A C; Merlen, E; Demerle, C; Dewailly, D

    2003-12-01

    Polycystic ovary syndrome (PCOS) and hypothalamic amenorrhea (HA) are the most frequent causes of endocrine infertility, but their association is an uncommon occurrence. We report the case of a 28-year old woman suffering from infertility and amenorrhea. Her weight was normal (BMI = 19) and she had no hirsutism. She self-reported food restriction and a 10 kg weight loss 5 years ago, concomitant with the onset of amenorrhea. At the initial evaluation, the patient was considered as having HA due to food restriction. At ultrasonography, ovaries were small and multifollicular (right and left area: 2.2 and 2.5 cm(2), respectively; number of cysts 2-9 mm in diameter: 15 and 12, respectively), and no stromal hypertrophy was noted. She has been treated for 1 month by intravenous pulsatile GnRH administration. Although the doses were increased from 5 to 15 microg/pulse every 90 min, no E2 response and no follicular development were observed. Hormonal re-evaluation revealed normal levels of serum LH, FSH and androgens, and a normal LH/FSH ratio. However, a typical aspect of PCO was found at ultrasound (right and left area: 6.5 and 5.5 cm(2), respectively, and more than 15 small cysts arranged peripherally around an increased central stroma in each ovary). The treatment has been then switched to hMG, using the low dose step-up regimen and starting with 75 U/day. In the absence of response after 2 weeks, the dose was increased to 112.5 U/day and a multifollicular reaction occurred, leading to cancellation. In conclusion, we hypothesize that this patient had a "hidden" PCOS when she was hypogonadotrophic and that it developed very rapidly after restitution of a normal gonadotropin level under exogenous GnRH. This occurred despite a low insulin level, showing that hyperinsulinism is not a prerequisite for the development of PCOS in every case.

  5. The environmental regulation of maturation in goldfish, Carassius auratus: effects of various LED light spectra.

    PubMed

    Shin, Hyun Suk; Habibi, Hamid R; Choi, Cheol Young

    2014-02-01

    While there have been a number of studies on the effects of photoperiod and duration of light and dark exposure, much less information is available on the importance of light intensity. This study investigated the effects of exposure of goldfish, Carassius auratus exposed to white fluorescent bulbs, and red (peak at 630nm), and green (530nm) light emitting diodes (LEDs) at approximately 0.9W/m(2) (12-h light:12-h dark) for four months on a number of hormones of the hypothalamus-pituitary-gonad (HPG) axis, in vivo and in vitro. We investigated the effects of native GnRH molecules (gonadotropin-releasing hormones; salmon GnRH, sGnRH; and chicken GnRH-II, cGnRH-II), gonadotropin hormones (GTHα; follicle-stimulating hormone, FSH-β; luteinizing hormone, LH-β2), kisspeptin 1 (Kiss1) and G protein-coupled receptor 54 (GPR54) mRNA levels. Furthermore, we measured LH and 17α-hydroxypregnenolone levels in plasma and we performed gonad histological observations. GnRHs, Kiss1, GPR54 and GTH mRNA and plasma LH and 17α-hydroxypregnenolone levels in the in vivo and in vitro groups exposed to green LEDs were significantly higher than the other groups. Histological analysis revealed the presence of oocytes in the yolk stage in fish exposed to green light. These results suggest that green wavelengths regulate the HPG axis and enhance sexual maturation in goldfish. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Luteinizing hormone stimulates mammalian target of rapamycin signaling in bovine luteal cells via pathways independent of AKT and mitogen-activated protein kinase: modulation of glycogen synthase kinase 3 and AMP-activated protein kinase.

    PubMed

    Hou, Xiaoying; Arvisais, Edward W; Davis, John S

    2010-06-01

    LH stimulates the production of cAMP in luteal cells, which leads to the production of progesterone, a hormone critical for the maintenance of pregnancy. The mammalian target of rapamycin (MTOR) signaling cascade has recently been examined in ovarian follicles where it regulates granulosa cell proliferation and differentiation. This study examined the actions of LH on the regulation and possible role of the MTOR signaling pathway in primary cultures of bovine corpus luteum cells. Herein, we demonstrate that activation of the LH receptor stimulates the phosphorylation of the MTOR substrates ribosomal protein S6 kinase 1 (S6K1) and eukaryotic translation initiation factor 4E binding protein 1. The actions of LH were mimicked by forskolin and 8-bromo-cAMP. LH did not increase AKT or MAPK1/3 phosphorylation. Studies with pathway-specific inhibitors demonstrated that the MAPK kinase 1 (MAP2K1)/MAPK or phosphatidylinositol 3-kinase/AKT signaling pathways were not required for LH-stimulated MTOR/S6K1 activity. However, LH decreased the activity of glycogen synthase kinase 3Beta (GSK3B) and AMP-activated protein kinase (AMPK). The actions of LH on MTOR/S6K1 were mimicked by agents that modulated GSK3B and AMPK activity. The ability of LH to stimulate progesterone secretion was not prevented by rapamycin, a MTOR inhibitor. In contrast, activation of AMPK inhibited LH-stimulated MTOR/S6K1 signaling and progesterone secretion. In summary, the LH receptor stimulates a unique series of intracellular signals to activate MTOR/S6K1 signaling. Furthermore, LH-directed changes in AMPK and GSK3B phosphorylation appear to exert a greater impact on progesterone synthesis in the corpus luteum than rapamycin-sensitive MTOR-mediated events.

  7. Generation of whistler waves by continuous HF heating of the upper ionosphere

    NASA Astrophysics Data System (ADS)

    Vartanyan, A.; Milikh, G. M.; Eliasson, B.; Najmi, A. C.; Parrot, M.; Papadopoulos, K.

    2016-07-01

    Broadband VLF waves in the frequency range 7-10 kkHz and 15-19 kHz, generated by F region CW HF ionospheric heating in the absence of electrojet currents, were detected by the DEMETER satellite overflying the High Frequency Active Auroral Research Program (HAARP) transmitter during HAARP/BRIOCHE campaigns. The VLF waves are in a frequency range corresponding to the F region lower lybrid (LH) frequency and its harmonic. This paper aims to show that the VLF observations are whistler waves generated by mode conversion of LH waves that were parametrically excited by HF-pump-plasma interaction at the upper hybrid layer. The paper discusses the basic physics and presents a model that conjectures (1) the VLF waves observed at the LH frequency are due to the interaction of the LH waves with meter-scale field-aligned striations—generating whistler waves near the LH frequency; and (2) the VLF waves at twice the LH frequency are due to the interaction of two counterpropagating LH waves—generating whistler waves near the LH frequency harmonic. The model is supported by numerical simulations that show good agreement with the observations. The (Detection of Electromagnetic Emissions Transmitted from Earthquake Regions results and model discussions are complemented by the Kodiak radar, ionograms, and stimulated electromagnetic emission observations.

  8. Structure of the dimeric RC–LH1–PufX complex from Rhodobaca bogoriensis investigated by electron microscopy

    PubMed Central

    Semchonok, Dmitry A.; Chauvin, Jean-Paul; Frese, Raoul N.; Jungas, Colette; Boekema, Egbert J.

    2012-01-01

    Electron microscopy and single-particle averaging were performed on isolated reaction centre (RC)—antenna complexes (RC–LH1–PufX complexes) of Rhodobaca bogoriensis strain LBB1, with the aim of establishing the LH1 antenna conformation, and, in particular, the structural role of the PufX protein. Projection maps of dimeric complexes were obtained at 13 Å resolution and show the positions of the 2 × 14 LH1 α- and β-subunits. This new dimeric complex displays two open, C-shaped LH1 aggregates of 13 αβ polypeptides partially surrounding the RCs plus two LH1 units forming the dimer interface in the centre. Between the interface and the two half rings are two openings on each side. Next to the openings, there are four additional densities present per dimer, considered to be occupied by four copies of PufX. The position of the RC in our model was verified by comparison with RC–LH1–PufX complexes in membranes. Our model differs from previously proposed configurations for Rhodobacter species in which the LH1 ribbon is continuous in the shape of an S, and the stoichiometry is of one PufX per RC. PMID:23148268

  9. Role of B800 in carotenoid-bacteriochlorophyll energy and electron transfer in LH2 complexes from the purple bacterium Rhodobacter sphaeroides.

    PubMed

    Polívka, Tomas; Niedzwiedzki, Dariusz; Fuciman, Marcel; Sundström, Villy; Frank, Harry A

    2007-06-28

    The role of the B800 in energy and electron transfer in LH2 complexes has been studied using femtosecond time-resolved transient absorption spectroscopy. The B800 site was perturbed by application of lithium dodecyl sulfate (LDS), and comparison of treated and untreated LH2 complexes from Rhodobacter sphaeroides incorporating carotenoids neurosporene, spheroidene, and spheroidenone was used to explore the role of B800 in carotenoid to bacteriochlorophyll-a (BChla) energy transfer and carotenoid radical formation. Efficiencies of the S1-mediated energy transfer in the LDS-treated complexes were 86, 61, and 57% in the LH2 complexes containing neurosporene, spheroidene, and spheroidenone, respectively. Analysis of the carotenoid S1 lifetimes in solution, LDS-treated, and untreated LH2 complexes allowed determination of B800/B850 branching ratio in the S1-mediated energy transfer. It is shown that B800 is a major acceptor, as approximately 60% of the energy from the carotenoid S1 state is accepted by B800. This value is nearly independent of conjugation length of the carotenoid. In addition to its role in energy transfer, the B800 BChla is the only electron acceptor in the event of charge separation between carotenoid and BChla in LH2 complexes, which is demonstrated by prevention of carotenoid radical formation in the LDS-treated LH2 complexes. In the untreated complexes containing neurosporene and spheroidene, the carotenoid radical is formed with a time constant of 300-400 fs. Application of different excitation wavelengths and intensity dependence of the carotenoid radical formation showed that the carotenoid radical can be formed only after excitation of the S2 state of carotenoid, although the S2 state itself is not a precursor of the charge-separated state. Instead, either a hot S1 state or a charge-transfer state lying between S2 and S1 states of the carotenoid are discussed as potential precursors of the charge-separated state.

  10. An Evaluation of LH-Stimulated Testosterone Production by ...

    EPA Pesticide Factsheets

    An Evaluation of LH-Stimulated Testosterone Production by Highly Purified Rat Leydig Cells: A Complementary Screen for Steroidogenesis in the Testis. 1Botteri, N., 2Suarez, J., 2Laws, S., 2Klinefelter, G.1Oak Ridge Institute for Science and Education, Oak Ridge, TN, 2 U.S. Environmental Protection Agency, ORD, NHEERL, TAD, RTP, NCThe H295R steroidogenesis assay uses an adrenocarcinoma cell line which fails to elicit LH mediated responses. This limits the assay’s ability to detect chemicals which disrupt LH-mediated Leydig cell responses in the testis. This study evaluated whether LH-stimulated T production by purified rat Leydig cells would be altered after exposure to chemicals that failed to decrease T production in the ToxCast H295R screen. Ten chemicals negative for T inhibition in the H295R screen, were selected based on alterations in upstream substrates (deoxycorticosterone, hydroxyprogesterone) expected to result in a decrease in T. Based on earlier work, simvastatin served as our positive control. Each chemical was tested over 6 concentrations ranging from 0.1 µM to 100 µM. Leydig cells were cultured overnight under maximal LH stimulation. A minimum of 3 replicate experiments were conducted for each format (24 and 96 well) and chemical tested; cell viability was assessed using a live/dead cytotoxicity kit. T data were excluded if viability was less than 80% of control. Initial evaluation using a 24-well Leydig cell assay confir

  11. Highly potent analogues of luteinizing hormone-releasing hormone containing D-phenylalanine nitrogen mustard in position 6.

    PubMed Central

    Bajusz, S; Janaky, T; Csernus, V J; Bokser, L; Fekete, M; Srkalovic, G; Redding, T W; Schally, A V

    1989-01-01

    The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Of the peptides prepared, [D-Mel6]LH-RH (SB-05) and [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,Arg5,D-Mel6,D-Ala10++ +]LH-RH [SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine] possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel6 analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells. PMID:2548207

  12. Highly potent analogues of luteinizing hormone-releasing hormone containing D-phenylalanine nitrogen mustard in position 6.

    PubMed

    Bajusz, S; Janaky, T; Csernus, V J; Bokser, L; Fekete, M; Srkalovic, G; Redding, T W; Schally, A V

    1989-08-01

    The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Of the peptides prepared, [D-Mel6]LH-RH (SB-05) and [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,Arg5,D-Mel6,D-Ala10++ +]LH-RH [SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine] possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel6 analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells.

  13. Impact of Laterality on Surgical Outcome of Glioblastoma Patients: A Retrospective Single-Center Study.

    PubMed

    Coluccia, Daniel; Roth, Tabitha; Marbacher, Serge; Fandino, Javier

    2018-06-01

    Resection of left hemisphere (LH) tumors is often complicated by the risks of causing language dysfunction. Although neurosurgeons' concerns when operating on the presumed dominant hemisphere are well known, literature evaluating laterality as a predictive surgical parameter in glioblastoma (GB) patients is sparse. We evaluated whether tumor laterality correlated with surgical performance, functional outcome, and survival. All patients with GB treated at our institution between 2006 and 2016 were reviewed. Analysis comprised clinical characteristics, extent of resection (EOR), neurologic outcome, and survival in relation to tumor lateralization. Two hundred thirty-five patients were included. Right hemisphere (RH) tumors were larger and more frequently extended into the frontal lobe. Preoperatively, limb paresis was more frequent in RH, whereas language deficits were more frequent in LH tumors (P = 0.0009 and P < 0.0001, respectively). At 6 months after resection, LH patients presented lower Karnofsky Performance Status (KPS) score (P = 0.036). More patients with LH tumors experienced dysphasia (P < 0.0001), and no difference was seen for paresis. Average EOR was comparable, but complete resection was achieved less often in LH tumors (37.7 vs. 64.8%; P = 0.0028). Although overall survival did not differ between groups, progression-free survival was shorter in LH tumors (7.4 vs. 10.1 months; P = 0.0225). Patients with LH tumors had a pronounced KPS score decline and shorter progression-free survival without effects on overall survival. This observation might partially be attributed to a more conservative surgical resection. Further investigation is needed to assess whether systematic use of awake surgery and intraoperative mapping results in increased EOR and improved quality survival of patients with GB. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. On the interaction of luminol with human serum albumin: Nature and thermodynamics of ligand binding

    NASA Astrophysics Data System (ADS)

    Moyon, N. Shaemningwar; Mitra, Sivaprasad

    2010-09-01

    The mechanism and thermodynamic parameters for the binding of luminol (LH 2) with human serum albumin was explored by steady state and picosecond time-resolved fluorescence spectroscopy. It was shown that out of two possible LH 2 conformers present is solution, only one is accessible for binding with HSA. The thermodynamic parameters like enthalpy (Δ H) and entropy (Δ S) change corresponding to the ligand binding process were also estimated by performing the experiment at different temperatures. The ligand replacement experiment with bilirubin confirms that LH 2 binds into the sub-domain IIA of the protein.

  15. Performance Tests of a Liquid Hydrogen Propellant Densification Ground System for the X33/RLV

    NASA Technical Reports Server (NTRS)

    Tomsik, Thomas M.

    1997-01-01

    A concept for improving the performance of propulsion systems in expendable and single-stage-to-orbit (SSTO) launch vehicles much like the X33/RLV has been identified. The approach is to utilize densified cryogenic liquid hydrogen (LH2) and liquid oxygen (LOX) propellants to fuel the propulsion stage. The primary benefit for using this relatively high specific impulse densified propellant mixture is the subsequent reduction of the launch vehicle gross lift-off weight. Production of densified propellants however requires specialized equipment to actively subcool both the liquid oxygen and liquid hydrogen to temperatures below their normal boiling point. A propellant densification unit based on an external thermodynamic vent principle which operates at subatmospheric pressure and supercold temperatures provides a means for the LH2 and LOX densification process to occur. To demonstrate the production concept for the densification of the liquid hydrogen propellant, a system comprised of a multistage gaseous hydrogen compressor, LH2 recirculation pumps and a cryogenic LH2 heat exchanger was designed, built and tested at the NASA Lewis Research Center (LeRC). This paper presents the design configuration of the LH2 propellant densification production hardware, analytical details and results of performance testing conducted with the hydrogen densifier Ground Support Equipment (GSE).

  16. Impaired testicular function in rats with diet-induced hypercholesterolemia and/or streptozotocin-induced diabetes mellitus.

    PubMed

    Tanaka, M; Nakaya, S; Kumai, T; Watanabe, M; Matsumoto, N; Kobayashi, S

    2001-01-01

    Hypercholesterolemia and diabetes mellitus are known to be accompanied by reproductive dysfunction. In this study, we investigated the effects of hypercholesterolemia, hyperglycemia, and these conditions combined, on testosterone (T) and testicular luteinizing hormone/human chorionic gonadotropin (LH/hCG) binding. Sprague-Dawley rats (8 weeks old) were divided into four groups: Group 1 was the control, group 2 was fed standard chow containing 2% cholesterol (C-diet), group 3 was administered streptozotocin (STZ, 65 mg/kg, i.p.), group 4 was treated with both the C-diet and STZ. After 4 weeks, rats were sacrificed. Serum glucose was significantly higher in the STZ group (304% that of controls) and the C-diet plus STZ group (345%), but there was no difference between the C-diet group (89%) and the control group. Serum cholesterol was significantly higher in the C-diet group (206% that of controls), the STZ group (452%) and the C-diet plus STZ group (2042%). Serum T, testicular T, and LH/hCG binding were significantly lower in the C-diet group (49%, 52%, and 81% that of controls, respectively), the STZ group (15%, 32%, and 72%) and the C-diet plus STZ group (8%, 21%, and 57%). These results suggest that hypercholesterolemia is an independent risk factor for testicular dysfunction and that the reduction of serum and testicular T levels is due at least in part to a reduction in testicular LH/hCG binding in rats with hypercholesterolemia, hyperglycemia, and these conditions combined. It is further suggested that the reduction in LH/hCG binding is mainly related to a rise in serum cholesterol levels.

  17. The right hemisphere is independent from the left hemisphere in allocating visuospatial attention.

    PubMed

    Zuanazzi, Arianna; Cattaneo, Luigi

    2017-07-28

    The capacity to allocate visuospatial attention is traditionally considered right-lateralized according to the effects of unilateral cerebral lesions. Contralateral hemi-spatial neglect occurs much more frequently after lesions of the right hemisphere, which has therefore been dubbed as 'dominant'. This pattern of symptoms is supported by functional models that postulate either independence or reciprocal influences between the two hemispheres. Here we specifically explored the dependency of the right hemisphere (RH) from the left hemisphere (LH) in spatial attention. We capitalized on the well-known effect of online transcranial magnetic stimulation (TMS) on the RH in healthy individuals, consisting in transient neglect-like manifestations in the left hemi-space. We assessed whether prior stimulation of the left posterior parietal cortex with a long-lasting neuromodulatory procedure (transcranial direct current stimulation - tDCS) affected the acute effects of TMS on the right posterior parietal cortex. We performed a within-subjects factorial study with two factors: LH tDCS (sham or real) and RH TMS (sham or real), resulting in a 2×2 design. The effects on spatial attention were examined separately for the two hemi-spaces by means of a modified line-bisection task. The results indicated that TMS over the RH produced a spatial attention deficit in the left hemi-space alone and the behavioural effects of TMS were not modulated by prior stimulation of the LH. Interestingly, additional analyses showed that tDCS over the LH alone produced a deficit in spatial attention to the right hemi-space. We interpret the current results as evidence for a largely independent contribution of each hemisphere to the allocation of visuospatial attention limited to the contralateral hemi-space. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Influence of sodium valproate on medium-late luteal phase pulsatile LH secretion in normal women.

    PubMed

    Lado Abeal, J; Rey Losada, C; Cabezas Agricola, J M; Cabezas-Cerrato, J

    1994-01-01

    It is not known whether gamma-aminobutyric acid (GABA) is involved in control of pulsatile LH secretion in human beings. Previous work by our group has shown that manipulation of the GABAergic system with sodium valproate does not affect pulsatile LH secretion in normal women in the late follicular phase. However, it has been suggested that steroid levels are critical for the influence of GABA upon hormone secretion; in particular, progesterone has been said to enhance inhibition by GABA. In this work we studied the effect of sodium valproate on pulsatile LH secretion in medium-late luteal phase of normal women. Six normal young women were studied over an 8-hour period in two successive menstrual cycles. On each occasion blood samples were taken every 10 minutes between 1000 and 1800 h. We administered 400 mg of sodium valproate every 8 hours on the 7 days preceding their second cycle and additional 400 mg at 0900 and 1400 h on the day of the study. Ovulation day was estimated by means of serial ovarian ultrasound examinations and confirmed by serum progesterone concentrations. In each cycle, LH, oestradiol and progesterone were determined by radioimmunoassay and sodium valproate by repolarization fluorescence spectrophotometry. The series of LH levels was smoothed for 1-minute sampling periods by means of a spline function and analysed by means of a program developed in our laboratory and written in Fortran 77. The program deconvolved the signal and calculated the pulse area, pulse duration, interpulse interval and number of pulses. LH pulse identification on the deconvolved signals was performed using our own method based on Friedman's non-parametric statistic. The statistical significance of differences between parameters was estimated using the Mann-Whitney test and Wilcoxon signed rank test. There were no significant differences in LH pulse area, pulse duration, interpulse interval or number of pulses with the administration of sodium valproate. Activation of the GABAergic system with sodium valproate had no biologically significant effect on the mid-late luteal phase pulsatile LH secretion in normal women.

  19. A Chaperone Complex Formed by HSP47, FKBP65 and BiP Modulates Telopeptide Lysyl Hydroxylation of Type I Procollagen

    PubMed Central

    Duran, Ivan; Martin, Jorge H.; Weis, Mary Ann; Krejci, Pavel; Konik, Peter; Li, Bing; Alanay, Yasemin; Lietman, Caressa; Lee, Brendan; Eyre, David; Cohn, Daniel H.; Krakow, Deborah

    2017-01-01

    Lysine hydroxylation of type I collagen telopeptides varies from tissue to tissue and these distinct hydroxylation patterns modulate collagen crosslinking to generate a unique extracellular matrix. Abnormalities in these patterns contribute to pathologies that include osteogenesis imperfecta (OI), fibrosis and cancer. Telopeptide procollagen modifications are carried out by lysyl hydroxylase 2 (LH2), however, little is known regarding how this enzyme regulates hydroxylation patterns. We identified an ER complex of resident chaperones that includes HSP47, FKBP65 and BiP regulating the activity of LH2. Our findings show that FKBP65 and HSP47 modulate the activity of LH2 to either favor or repress its activity. BiP was also identified as a member of the complex, playing a role in enhancing the formation of the complex. This newly identified ER chaperone complex contributes to our understanding of how LH2 regulates lysyl hydroxylation of type I collagen C-telopeptides to affect the quality of connective tissues. PMID:28177155

  20. The NMR solution structure of a mutant of the Max b/HLH/LZ free of DNA: insights into the specific and reversible DNA binding mechanism of dimeric transcription factors.

    PubMed

    Sauvé, Simon; Tremblay, Luc; Lavigne, Pierre

    2004-09-17

    Basic region-helix1-loop-helix2-leucine zipper (b/H(1)LH(2)/LZ) transcription factors bind specific DNA sequence in their target gene promoters as dimers. Max, a b/H(1)LH(2)/LZ transcription factor, is the obligate heterodimeric partner of the related b/H(1)LH(2)/LZ proteins of the Myc and Mad families. These heterodimers specifically bind E-box DNA sequence (CACGTG) to activate (e.g. c-Myc/Max) and repress (e.g. Mad1/Max) transcription. Max can also homodimerize and bind E-box sequences in c-Myc target gene promoters. While the X-ray structure of the Max b/H(1)LH(2)/LZ/DNA complex and that of others have been reported, the precise sequence of events leading to the reversible and specific binding of these important transcription factors is still largely unknown. In order to provide insights into the DNA binding mechanism, we have solved the NMR solution structure of a covalently homodimerized version of a Max b/H(1)LH(2)/LZ protein with two stabilizing mutations in the LZ, and characterized its backbone dynamics from (15)N spin-relaxation measurements in the absence of DNA. Apart from minor differences in the pitch of the LZ, possibly resulting from the mutations in the construct, we observe that the packing of the helices in the H(1)LH(2) domain is almost identical to that of the two crystal structures, indicating that no important conformational change in these helices occurs upon DNA binding. Conversely to the crystal structures of the DNA complexes, the first 14 residues of the basic region are found to be mostly unfolded while the loop is observed to be flexible. This indicates that these domains undergo conformational changes upon DNA binding. On the other hand, we find the last four residues of the basic region form a persistent helical turn contiguous to H(1). In addition, we provide evidence of the existence of internal motions in the backbone of H(1) that are of larger amplitude and longer time-scale (nanoseconds) than the ones in the H(2) and LZ domain. Most interestingly, we note that conformers in the ensemble of calculated structures have highly conserved basic residues (located in the persistent helical turn of the basic region and in the loop) known to be important for specific binding in a conformation that matches that of the DNA-bound state. These partially prefolded conformers can directly fit into the major groove of DNA and as such are proposed to lie on the pathway leading to the reversible and specific DNA binding. In these conformers, the conserved basic side-chains form a cluster that elevates the local electrostatic potential and could provide the necessary driving force for the generation of the internal motions localized in the H(1) and therefore link structural determinants with the DNA binding function. Overall, our results suggests that the Max homodimeric b/H(1)LH(2)/LZ can rapidly and preferentially bind DNA sequence through transient and partially prefolded states and subsequently, adopt the fully helical bound state in a DNA-assisted mechanism or induced-fit.

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