bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Power and Robustness of Maximum LOD Score Statistics
Authors: Yoo Y. J. , Mendell N. R. 
Published: April 2008

SummaryThe maximum LOD score statistic is extremely powerful for gene mapping when calculated using the correct genetic parameter value. When the mode of genetic transmission is unknown, the maximum of the LOD scores obtained using several genetic parameter values is reported. This latter statistic requires higher critical value than the maximum LOD score statistic calculated from a single genetic parameter value.In this paper, we compare the power of maximum LOD scores based on three fixed sets of genetic parameter values with the power of the LOD score obtained after maximizing over the entire range of genetic parameter values. We simulate family data under nine generating models. For generating models with non‐zero phenocopy rates, LOD scores maximized over the entire range of genetic parameters yielded greater power than maximum LOD scores for fixed sets of parameter values with zero phenocopy rates. No maximum LOD score was consistently more powerful than the others for generating models with a zero phenocopy rate. The power loss of the LOD score maximized over the entire range of genetic parameters, relative to the maximum LOD score calculated using the correct genetic parameter value, appeared to be robust to the generating models.
Bioenergy from plants and the sustainable yield challenge
Authors: Karp Angela , Shield Ian 
Published: April 2008

SummaryBioenergy from plants, particularly from perennial grasses and trees, could make a substantial contribution to alleviation of global problems in climate change and energy security if high yields can be sustained. Here, yield traits in a range of key bioenergy crops are reviewed, from which several targets for future improvement can be identified. Some are already the focus of genetically modified (GM) and non‐GM approaches. However, the efficient growth strategies of perennial bioenergy crops rely on newly assimilated and recycled carbon and remobilized nitrogen in a continually shifting balance between sources and sinks. This balance is affected by biotic (e.g. pest, disease) and abiotic (e.g. drought) stresses. Future research should focus on three main challenges: changing (photo)thermal time sensitivity to lengthen the growing season without risking frost damage or limiting remobilization of nutritional elements following senescence; increasing aboveground biomass without depleting belowground reserves required for next year's growth and thus without increasing the requirement for nutrient applications; and increasing aboveground biomass without increasing water use.ContentsSummary1I.Introduction1II.Bioenergy, biomass and biofuel crops2III.  Bioenergy yield traits2IV.Bioenergy composition traits8V.Sustainable bioenergy production from crops9VI.  Increasing bioenergy yields in a sustainable way10VII.Conclusions and perspectives12Acknowledgements13References13
Endothelial nitric oxide synthase overexpression by neuronal cells in neurodegeneration: a link between inflammation and neuroprotection
Authors: De Palma Clara , Falcone Sestina , Panzeri Chris , Radice Sonia , Bassi Maria Teresa , Clementi Emilio 
Published: April 2008

AbstractThe roles of neuronal and inducible nitric oxide synthases in neurones have been extensively investigated; by contrast, the biological significance of endothelial nitric oxide synthase (eNOS) overexpression that occurs in several pathological conditions has not yet been studied. We have started addressing this issue in a cell model of neurodegeneration, i.e. human SKNBE neuroblastoma cells transfected with a mutant form of alsin, a protein causing an early‐onset type of amyotrophic lateral sclerosis, ALS2. We found that eNOS, which is endogenously expressed by these cells, was activated by tumour necrosis factor‐α (TNF‐α), a proinflammatory cytokine that plays important roles in ALS2 and several neurodegenerative diseases. The TNF‐α‐dependent eNOS activation occurred through generation, by sphingosine‐kinase‐1, of sphingosine‐1‐phosphate, stimulation of its membrane receptors and activation of Akt, as determined using small interference RNA and dominant negative constructs specific for the enzymes and receptors. eNOS activation by TNF‐α conferred cytoprotection from excitotoxicity and neurotoxic cues such as reactive oxygen species, endoplasmic reticulum stress, DNA damage, and mutated alsin itself. Our results suggest that overexpression of eNOS by neurones is a broad‐range protective mechanism activated during damage and establish a link of pathophysiological relevance between this enzyme and inflammation accompanying neurodegenerative diseases. These findings also question the concept that high NO output in the presence of oxidative stress leads always to peroxynitrite formation contributing to neurodegeneration.
Characterization of OPA1 isoforms isolated from mouse tissues
Authors: Akepati Vasudheva Reddy , Müller Eva‐Christina , Otto Albrecht , Strauss Holger M. , Portwich Michael , Alexander Christiane 
Published: April 2008

AbstractOPA1, a nuclear encoded mitochondrial protein causing autosomal dominant optic atrophy, is a key player in mitochondrial fusion and cristae morphology regulation. In the present study, we have compared the OPA1 transcription and translation products of different mouse tissues. Unlike in humans, we found only two exons (4b and 5b) to be involved in alternative splicing. The relative abundance of the resulting four different splice variants is tissue‐dependent. Proteolytic cleavage by mitochondrial processing peptidase generates two long forms, isoforms 1 and 7, which lead to three short forms representing the end products after further proteolytic processing. In contrast, isoforms 5 and 8 are directly processed into their corresponding short forms. Short form 1 molecules form 184 kDa dimers, whereas all other isoforms contribute to 285 kDa complexes. Coiled‐coil domains of the OPA1 protein specifically homo‐associate and may be involved in the formation of these complexes. Furthermore, the region encoded by exon 5b inhibits the self‐association of coiled‐coil domain‐I. Finally, our data pinpoint isoform 1 as the, by far, most abundant isoform in the nervous tissue. We postulate that manipulation of isoform 1 protein levels in relation to the other isoforms induces changes in the mitochondrial network in the cell and therefore, mutations affecting the level of functional isoform 1 could lead to devastating effects on retinal ganglion cells.
Brain metabolism in adult chronic hydrocephalus
Authors: Kondziella Daniel , Sonnewald Ursula , Tullberg Mats , Wikkelso Carsten 
Published: April 2008

AbstractNormal pressure hydrocephalus (NPH) is the most frequent form of chronic hydrocephalus in adults. NPH remains underdiagnosed although between 5% and 10% of all demented patients may suffer from this disorder. As dementia is an increasing demographic problem, treatable forms such as in NPH have become a central issue in neurology. Despite the traditional perception of hydrocephalus being a disorder of disturbed CSF dynamics, in NPH metabolic impairment seems at least as important. So far, the only valid animal model of NPH is chronic adult kaolin hydrocephalus. In this model, opening of alternative CSF outflow pathways leads to normal or near‐normal intracranial pressure and CSF outflow resistance. Yet, various metabolic disturbances cause ongoing ventricular enlargement and characteristic symptoms including cognitive decline and gait ataxia. Delayed hippocampal neuronal death, accumulation of beta‐amyloid and disturbed cholinergic neurotransmission may contribute to memory dysfunction. Compromised periventricular blood flow, decreased dopamine levels in the substantia nigra and damaged striatal GABAergic interneurons may reflect basal ganglia symptoms. At least in human hydrocephalus cerebrovascular co‐morbidity of the white matter plays an important role as well. It seems that in hydrocephalus from a certain ‘point of no return’ metabolic impairment becomes decoupled from CSF dynamics and, at least partly, self‐sustained. This is probably the reason why despite restored CSF circulation by shunting many patients with chronic hydrocephalus still suffer from severe neurological deficits. The present paper offers a comprehensive review of the experimental and clinical data suggesting metabolic disturbances in chronic hydrocephalus.
Tetrahydrobiopterin shows chaperone activity for tyrosine hydroxylase
Authors: Thöny Beat , Calvo Ana C. , Scherer Tanja , Svebak Randi M. , Haavik Jan , Blau Nenad , Martinez Aurora 
Published: April 2008

AbstractTyrosine hydroxylase (TH) is the rate‐limiting enzyme in the synthesis of catecholamine neurotransmitters. Primary inherited defects in TH have been associated with l‐DOPA responsive and non‐responsive dystonia and infantile parkinsonism. In this study, we show that both the cofactor (6R)‐l‐erythro‐5,6,7,8‐tetrahydrobiopterin (BH4) and the feedback inhibitor and catecholamine product dopamine increase the kinetic stability of human TH isoform 1 in vitro. Activity measurements and synthesis of the enzyme by in vitro transcription–translation revealed a complex regulation by the cofactor including both enzyme inactivation and conformational stabilization. Oral BH4 supplementation to mice increased TH activity and protein levels in brain extracts, while the Th‐mRNA level was not affected. All together our results indicate that the molecular mechanisms for the stabilization are a primary folding‐aid effect of BH4 and a secondary effect by increased synthesis and binding of catecholamine ligands. Our results also establish that orally administered BH4 crosses the blood–brain barrier and therapeutic regimes based on BH4 supplementation should thus consider the effect on TH. Furthermore, BH4 supplementation arises as a putative therapeutic agent in the treatment of brain disorders associated with TH misfolding, such as for the human TH isoform 1 mutation L205P.
Histamine induces neural stem cell proliferation and neuronal differentiation by activation of distinct histamine receptors
Authors: Molina‐Hernández Anayansi , Velasco Iván 
Published: April 2008

AbstractHistamine has neurotransmitter/neuromodulator functions in the adult brain, but its role during CNS development has been elusive. We studied histamine effects on proliferation, cell death and differentiation of neuroepithelial stem cells from rat cerebral cortex in vitro. RT‐PCR and Western blot experiments showed that proliferating and differentiated cells express histamine H1, H2 and H3 receptors. Treatments with histamine concentrations (100 nM–1 mM) caused significant increases in cell numbers without affecting Nestin expression. Cell proliferation was evaluated by BrdU incorporation; histamine caused a significant increase dependent on H2 receptor activation. Apoptotic cell death during proliferation was significantly decreased at all histamine concentrations, and cell death was promoted in a concentration‐dependent manner by histamine in differentiated cells. Immunocytochemistry studies showed that histamine increased 3‐fold the number of neurons after differentiation, mainly by activation of H1 receptor, and also significantly decreased the glial (astrocytic) cell proportion, when compared to control conditions. In summary, histamine increases cell number during proliferative conditions, and has a neuronal‐differentiating action on neural stem cells, suggesting that the elevated histamine concentration reported during development might play a role in cerebrocortical neurogenesis, by activation of H2 receptors to promote proliferation of neural precursors, and favoring neuronal fate by H1‐mediated stimulation.
Pin1 promotes cell death in NGF‐dependent neurons through a mechanism requiring c‐Jun activity
Authors: Barone Maria Cecilia , Desouza Lynette A. , Freeman Robert S. 
Published: April 2008

AbstractDeveloping neurons deprived of trophic support undergo apoptosis mediated by activation of c‐Jun N‐terminal kinases (JNK) and c‐Jun, induction of the Bcl‐2 homology 3‐only protein BimEL, Bax‐dependent loss of mitochondrial cytochrome c, and caspase activation. However, the mechanisms that regulate each of these events are only partially understood. Here we show that the prolyl isomerase Pin1 functions as a positive regulator of neuronal death through a c‐Jun‐dependent mechanism. Ectopic Pin1 promoted caspase‐dependent death of NGF‐maintained neurons that was associated with an accumulation of Ser63‐phosphorylated c‐Jun in neuronal nuclei and was partially dependent on Bax. Downregulating Pin1 prior to NGF withdrawal suppressed the accumulation of phosphorylated c‐Jun, inhibited the release of cytochrome c, and significantly delayed cell death. Pin1 knockdown inhibited NGF deprivation‐induced death to a similar extent in Bim (+/+) and Bim (−/−) neurons. The protective effect of Pin1 knockdown was significantly greater than that caused by loss of Bim and nearly identical to that caused by a dominant negative form of c‐Jun. Finally, cell death induced by ectopic Pin1 was largely blocked by expression of dominant negative c‐Jun. These results suggest a novel mechanism by which Pin1 promotes cell death involving activation of c‐Jun.
Age‐related increase of superoxide generation in the brains of mammals and birds
Authors: Sasaki Toru , Unno Keiko , Tahara Shoichi , Shimada Atsuyoshi , Chiba Yoichi , Hoshino Minoru , Kaneko Takao 
Published: April 2008

SummaryOxidative stress, an imbalance between endogenous levels of oxygen radicals and antioxidative defense, increases with aging. However, it is not clear which of these two factors is the more critical. To clarify the production of oxygen radicals increases with age, we examined oxygen radical‐dependent chemiluminescent signals in ex vivo brain slices using a novel photonic imaging method. The chemiluminescent intensity was significantly decreased by the membrane permeable superoxide dismutase (SOD)/catalase mimic, but not by Cu,Zn‐SOD. Inhibitors for complex I, III, and IV of the mitochondrial electron transport chain transiently enhanced the chemiluminescent signal. The superoxide‐dependent chemiluminescent intensity in senescence accelerated mouse (SAM) brain tissues increases with age. Moreover, the slope of the age‐dependent increase was steeper in SAMP10, a strain characterized by a short lifespan and atrophy in the frontal cerebral cortex, than the senescence‐resistant strain SAMR1, which has a longer lifespan. An increase in chemiluminescence with age was also observed in C57/BL6 mice, Wistar rats, and pigeons, although levels of chemiluminescence were lower in the pigeons than murines. The rate of age‐related increases of superoxide‐dependent chemiluminescence was inversely related to the maximum lifespan of the animals. The activity of superoxide dismutase was unchanged during the aging process in the brain. This suggested that superoxide production itself may increase with age. We speculated that reactive oxygen may be a signal to determine the aging process.
Apolipoprotein D is involved in the mechanisms regulating protection from oxidative stress
Authors: Ganfornina Maria D. , Do Carmo Sonia , Lora Jose M. , Torres‐Schumann Sonia , Vogel Marci , Allhorn Maria , González Constancio , Bastiani Michael J. , Rassart Eric , Sanchez Diego 
Published: April 2008

SummaryMany nervous system pathologies are associated with increased levels of apolipoprotein D (ApoD), a lipocalin also expressed during normal development and aging. An ApoD homologous gene in Drosophila, Glial Lazarillo, regulates resistance to stress, and neurodegeneration in the aging brain. Here we study for the first time the protective potential of ApoD in a vertebrate model organism. Loss of mouse ApoD function increases the sensitivity to oxidative stress and the levels of brain lipid peroxidation, and impairs locomotor and learning abilities. Human ApoD overexpression in the mouse brain produces opposite effects, increasing survival and preventing the raise of brain lipid peroxides after oxidant treatment. These observations, together with its transcriptional up‐regulation in the brain upon oxidative insult, identify ApoD as an acute response protein with a protective and therefore beneficial function mediated by the control of peroxidated lipids.
CLADISTIC ANALYSIS OF THE SUBORDER CONULARIINA MILLER AND GURLEY, 1896 (CNIDARIA, SCYPHOZOA; VENDIAN–TRIASSIC)
Authors: DE MORAES LEME JULIANA , GUIMARÃES SIMÕES MARCELLO , CARLOS MARQUES ANTONIO , VAN ITEN HEYO 
Published: April 2008

Abstract:  Results of a cladistic analysis of the suborder Conulariina Miller and Gurley, 1896, a major extinct (Vendian–Triassic) group of scyphozoan cnidarians, are presented. The analysis sought to test whether the three conulariid subfamilies (Conulariinae Walcott, 1886, Paraconulariinae Sinclair, 1952 and Ctenoconulariinae Sinclair, 1952) recognized in the Treatise on Invertebrate Paleontology (TIP) are monophyletic. A total of 17 morphological characters were scored for 16 ingroup taxa, namely the genera Archaeoconularia, Baccaconularia, Climacoconus, Conularia, Conulariella, Conularina, Ctenoconularia, Eoconularia, Glyptoconularia, Metaconularia, Notoconularia, Paraconularia, Pseudoconularia, Reticulaconularia, Teresconularia and Vendoconularia. The extant medusozoan taxa Cubozoa, Stauromedusae, Coronatae and Semaeostomeae served as outgroups. Unweighted analysisof the data matrix yielded 1057 trees, and successive weighting analysis resulted in one of the 1057 original trees. The ingroup is monophyletic with two autapomorphies: (1) the quadrate geometry of the oral region; and (2) the presence of a mineralized (phosphatic) periderm. Within the ingroup, the clade (Vendoconularia, Teresconularia, Conularina, Eoconularia) is supported by the sinusoidal longitudinal geometry of the transverse ridges, and the much larger clade (Baccaconularia, Glyptoconularia, Metaconularia, Pseudoconularia, Conularia, Ctenoconularia, Archaeoconularia, Notoconularia, Climacoconus, Paraconularia, Reticulaconularia) is supported by the presence of external tubercles, which, however, were lost in the clade (Notoconularia, Climacoconus, Paraconularia, Reticulaconularia). As proposed by Van Iten et al. (2000), the clade (Notoconularia, Climacoconus, Paraconularia, Reticulaconularia) is supported by the termination and alternation of the transverse ribs in the corner sulcus. The previously recognized subfamilies Conulariinae, Paraconulariinae and Ctenoconulariinae were not recovered from this analysis. The diagnostic features of Conulariinae (continuation of the transverse ornament across the corner sulcus and lack of carinae) and Ctenoconulariinae (presence of carinae) are symplesiomorphic or homoplastic, and Paraconulariinae is polyphyletic. The families Conulariellidae Kiderlen, 1937 and Conulariopsidae Sugiyama, 1942, also recognized in the TIP, are monogeneric, and since they provide no additional phylogenetic information, should be abandoned.
PHYLOGENETIC POSITION AND MORPHOLOGY OF THECAE AND CYSTS OF SCRIPPSIELLA (DINOPHYCEAE) SPECIES IN THE EAST CHINA SEA1
Authors: Gu Haifeng , Sun Jun , Kooistra Wiebe H. C. F. , Zeng Runying 
Published: April 2008

Resting cysts of the marine phytoplanktonic dinoflagellate Scrippsiella spp. are encountered in coastal habitats and shallow seas all over the world. Identification of Scrippsiella species requires information on cyst morphology because the plate pattern of the flagellated cell is conserved. Cysts from sediments of the East China Sea were identified based on traits from both the cysts and the thecal patterns of germinated cells. Calcareous cysts belonged predominantly to S. trochoidea (F. Stein) A. R. Loebl., S. rotunda J. Lewis, and S. precaria Montresor et Zingone. The former two species also produced smooth and noncalcified cysts in the field. A new species, S. donghaienis H. Gu sp. nov, was obtained from six noncalcified cysts with organic spines. These cysts are spherical, full of pale white and greenish granules with a mesoepicystal archeopyle. The vegetative cells consist of a conical epitheca and a round hypotheca with a plate formula of po, x, 4′, 3a, 7′′, 6c (5c + t), 6 s, 5′′′, 2′′′′ and are morphologically indistinguishable from S. trochoidea. Results of internal transcribed spacer (ITS) sequence comparisons revealed that S. donghaienis was distinct from the S. trochoidea complex and appeared nested within the Calciodinellum/Calcigonellum clade. Culture experiments showed that the presence of a red body in the cyst and the shape of the archeopyle were constant within cell lines from one generation to the next, while the morphological features of the cyst wall, such as calcification and spine shape, appeared to be phenotypically plastic.
NEW MARINE MEMBERS OF THE GENUS HEMISELMIS (CRYPTOMONADALES, CRYPTOPHYCEAE)1
Authors: Lane Christopher E. , Archibald John M. 
Published: April 2008

Cryptomonads are a ubiquitous and diverse assemblage of aquatic flagellates. The relatively obscure genus Hemiselmis includes some of the smallest of these cells. This genus contained only two species until 1967, when Butcher described seven new marine species mainly on the basis of observations with the light microscope. However, from these seven taxa, only H. amylifera and H. oculata were validly published. Additionally, the features Butcher used to distinguish species have since been questioned, and the taxonomy within Hemiselmis has remained clouded due to the difficulty in unambiguously applying his classification and validating many of his species. As a result, marine strains are often placed into one of three species—H. rufescens Parke, H. virescens Droop, or the invalid H. brunnescens Butcher—based on cell color alone. Here we applied microscopic and molecular tools to 13 publicly available Hemiselmis strains in an effort to clarify species boundaries. SEM failed to provide sufficient morphological variation to distinguish species of Hemiselmis, and results from LM did not correlate with clades found using both molecular phylogenetic and nucleomorph genome karyotype analysis, indicating a high degree of morphological plasticity within species. On the basis of molecular characters and collection geography we recognize four new marine species of Hemiselmis—H. cryptochromatica sp. nov., H. andersenii sp. nov., H. pacifica sp. nov., and H. tepida sp. nov.—from the waters around North America.