On the site of action of naloxone-stimulated cortisol secretion in gilts

The increase in serum cortisol concentrations following naloxone administration to female pigs was abolished by hypophysial stalk-transection, even though CRH and ACTH stimulated cortisol release in these animals. We suggest that the opioid antagonist enhances cortisol secretion primarily by a central action in pigs.     

Negative feedback as an obligatory antecedent to the estradiol-induced luteinizing hormone surge in ovariectomized pigs

In ovariectomized pigs, estradiol treatment induces a preovulatory-like luteinizing hormone (LH) surge, but only after serum LH concentrations are suppressed for 48 h. This inhibition of LH release is attributable in large part to inhibition of gonadotropin-releasing hormone (GnRH) release. The present report examines the dependency of the estradiol-induced LH surge on this preceding phase of negative feedback. Ten ovariectomized gilts were given an i.m. injection of estradiol benzoate (10 micrograms/kg BW). Beginning at the time of estradiol treatment, 5 of these gilts received 1-microgram GnRH pulses i.v. every 45 min for 48 h, i.e. during the period of negative feedback. The remaining 5 control gilts received comparable infusions of vehicle. Estradiol induced the characteristic biphasic LH response in control gilts. On the other hand, the inhibitory LH response to estradiol was prevented and the ensuing LH surge was blocked in 4 of the 5 gilts given GnRH pulses during the negative feedback phase. These results indicate that suppressing release of GnRH and/or LH is an important antecedent to full expression of the LH surge in ovariectomized pigs. Assimilation of this observation with the existing literature provides novel insights into the neuroendocrine control of LH secretion in castrated and ovary-intact gilts.     

Effective size,census size,and genetic monitoring of the endangered razorback sucker, <Emphasis Type="Italic">Xyrauchen texanus</Emphasis>

For the past several decades the Lake Mohave population of the federally endangered razorback sucker, Xyrauchen texanus, has had no natural recruitment because of intensive predation on larvae by non-native fishes. In response to impending extirpation, a repatriation program was implemented where larval razorbacks are collected from the wild following natural spawning, reared in protective custody, and then repatriated at a much larger size. In this study, we estimated annual (N _bf) and generational female effective size (N _ef) of the spawning stock by characterizing temporal genetic changes in mtDNA among larval cohorts, and then compared these estimates to the estimated number of reproductively capable (adult) females in Lake Mohave (N _f). Razorback suckers have life history and mortality schedules that could yield values of N _ef/N _f as low as 10⁻⁵ due to match–mismatch recruitment (or the “Hedgecock effect”) that increases variance in reproductive success. Average N _bf was estimated to be 160, N _ef was 706, and the ratio N _ef/N _f was 0.29 and 0.38 for arithmetic and harmonic mean N _f, respectively. Our findings indicate that (i) larval sampling in Lake Mohave sufficiently encompasses temporal and spatial variation within annual larval cohorts as to be representative of the spawning stock, (ii) roughly 3–16% (about 8% on average) of adult females contribute genetically to larval cohorts each year, and (iii) repatriated fishes appear to be contributing genetically to larval cohorts. Simultaneous genetic and demographic monitoring offers insights that neither approach can provide alone into effects of population decline and management practices in this species.     

Recrafting the neighbor-joining method

Background  

The neighbor-joining method by Saitou and Nei is a widely used method for constructing phylogenetic trees. The formulation of the method gives rise to a canonical Θ(n ³) algorithm upon which all existing implementations are based.     

Frasnian vertebrate taphonomy and sedimentology of macrofossil concentrations from the Langsēde Cliff,Latvia

Luk?evi?s, E., Ahlberg, P.E., Stinkulis, ?., Vasi?kova, J. & Zupi??, I. 2011: Frasnian vertebrate taphonomy and sedimentology of macrofossil concentrations from the Langsēde Cliff, Latvia. Lethaia, Vol. 45, pp. 356–370. The siliciclastic sequence of the Upper Devonian of Kurzeme, Western Latvia, is renowned for abundant vertebrate fossils, including the stem tetrapods Obruchevichthys gracilis and Ventastega curonica. During the first detailed taphonomic study of the vertebrate assemblage from the Ogre Formation cropping out at the Langsēde Cliff, Imula River, abundant vertebrate remains have been examined and identified as belonging to one psammosteid, two acanthodian and three sarcopterygian genera; the placoderm Bothriolepis maxima dominates the assemblage. Besides fully disarticulated placoderm and psammosteid plates, separate sarcopterygian scales and teeth, and acanthodian spines, partly articulated specimens including complete distal segments of Bothriolepis pectoral fins, Bothriolepis head shields and sarcopterygian lower jaws have been found. The size distribution of the placoderm bones demonstrates that the individuals within the assemblage are of approximately uniform age. Distinct zones have been traced within the horizontal distribution of the bones. These linear zones are almost perpendicular to the dominant dip azimuth of the cross‐beds and ripple‐laminae and most probably correspond to the depressions between subaqueous dunes. Concavity ratio varies significantly within the excavation area. The degree of fragmentation of the bones and disarticulation of the skeletons suggest that the carcasses were reworked and slightly transported before burial. Sedimentological data suggest deposition in a shallow marine environment under the influence of rapid currents. The fossiliferous bed consists of a basal bone conglomerate covered by a cross‐stratified sandstone with mud drapes, which is in turn overlain by ripple laminated sandstone, indicating the bones were buried by the gradual infilling of a tidal channel. All the Middle–Upper Devonian vertebrate bone‐beds from Latvia are associated with sandy to clayey deposits and have been formed in a sea‐coastal zone during rapid sedimentation episodes, but differ in fossil abundance and degree of preservation. □Agnathans, Devonian, facies analysis, fish, fossil assemblage, palaeoenvironment.     

Acute cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD

Impairment of working memory is one of the most important deleterious effects of marijuana intoxication in humans, but its underlying mechanisms are presently unknown. Here, we demonstrate that the impairment of spatial working memory (SWM) and in vivo long-term depression (LTD) of synaptic strength at hippocampal CA3-CA1 synapses, induced by an acute exposure of exogenous cannabinoids, is fully abolished in conditional mutant mice lacking type-1 cannabinoid receptors (CB(1)R) in brain astroglial cells but is conserved in mice lacking CB(1)R in glutamatergic or GABAergic neurons. Blockade of neuronal glutamate N-methyl-D-aspartate receptors (NMDAR) and of synaptic trafficking of glutamate α-amino-3-hydroxy-5-methyl-isoxazole propionic acid receptors (AMPAR) also abolishes cannabinoid effects on SWM and LTD induction and expression. We conclude that the impairment of working memory by marijuana and cannabinoids is due to the activation of astroglial CB(1)R and is associated with astroglia-dependent hippocampal LTD in vivo.     

A tree-based method for the rapid screening of chemical fingerprints

Background  

The fingerprint of a molecule is a bitstring based on its structure, constructed such that structurally similar molecules will have similar fingerprints. Molecular fingerprints can be used in an initial phase of drug development for identifying novel drug candidates by screening large databases for molecules with fingerprints similar to a query fingerprint.     

Isolation of citroylformic acid-gamma-lactone from a commerical batch of oxaloacetic acid: inhibition of apotyrosine aminotransferase conversion to holoenzyme by this substance.

Citroylformic acid-γ-lactone (CFA, 1-keto-2,4-dihydroxy-4-carboxyadipenoic acid(2–3)-1,4-lactone), isolated from a commercial batch of oxaloacetate, inhibited conversion of rat liver apotyrosine aminotransferase (EC 2.6.1.5) to holoenzyme. Using partially purified enzyme, the K_i was determined to be less than 0.7 mm. A more definitive K_i was difficult to obtain because at pH 7 CFA had a half-life of about 2 hr. Inhibition of the enzyme by CFA was stereospecific and reversible; the S (?) stereoisomer was approximately 10 times more inhibitory than its R(+) antipode, and over 90% of inhibited enzyme was recoverable after overnight dialysis. Preineubation of apotyrosine aminotransferase with its coenzyme (pyridoxal phosphate) prevented inhibition by CFA, and a substantial fraction of enzyme that had been inhibited by CFA could be readily reactivated by addition of high concentrations of pyridoxal phosphate. Studies with inhibitor analogs indicated that both a partially unsaturated lactone ring and a stereospecific carboxymethyl group are required for maximal inhibitory activity. The sodium salts of citroylformic acid and oxalopyruvic acid, formed by the hydrolysis of their respective lactones, were not inhibitory; 1-keto-2,4-dihydroxy-4-carboxyadipic acid-γ-lactone and little inhibitory activity, and 1-keto-2,4-dihydroxyglutarenoic acid-γ-lactone and 1-keto-2,4-dihydroxybutene-γ-lactone were somewhat better inhibitors than the R(+) stereoisomer of CFA. The possibility that CFA is a naturally occurring biological substance is discussed.     

Copper (II) complex-catalyzed oxidation of NADH by hydrogen peroxide

Among various metal ions of physiological interest, Cu²⁺ is uniquely capable of catalyzing the oxidation of NADH by H₂O₂. This oxidation is stimulated about fivefold in the presence of imidazole. A similar activating effect is found for some imidazole derivatives (1-methyl imidazole, 2-methyl imidazole, andN-acetyl-L-histidine). Some other imidazole-containing compounds (L-histidine,L-histidine methyl ester, andL-carnosine), however, inhibit the Cu²⁺-catalyzed peroxidation of NADH. Other chelating agents such as EDTA andL-alanine are also inhibitory. Stoichiometry for NADH oxidation per mole of H₂O₂ utilized is 1, which excludes the possibility of a two-step oxidation mechanism with a nucleotide free-radical intermediate. About 92% of the NADH oxidation product can be identified as enzymatically active NAD⁺. D₂O, 2,5-dimethylfuran, and 1,4-diazabicyclo [2.2.2]-octane have no significant effect on the oxidation, thus excluding¹O₂ as a mediator. Similarly, OH· is also not a likely intermediate, since the system is not affected by various scavengers of this radical. The results suggest that a copper-hydrogen peroxide intermediate, when complexed with suitable ligands, can generate still another oxygen species much more reactive than its parent compound, H₂O₂.