Pharmacological characterization of the effects of taurine on calcium uptake in the rat retina

Summary Taurine is known to increase ATP-dependent calcium ion (Ca²⁺) uptake in retinal membrane preparations and in isolated rod outer segments (ROS) under low calcium conditions (10M) (Pasantes-Morales and Ordóñez, 1982; Lombardini, 1991). In this report, ATP-dependent Ca²⁺ uptake in retinal membrane preparations was found to be inhibited by 5M cadmium (Cd²⁺), suggesting the involvement of cation channel activation. The activation of cGMP-gated cation channels, which are found in the ROS, is a crucial step in the phototransduction process. An inhibitor of cGMP-gated channels, LY83583, was found to inhibit taurine-stimulated ATP-dependent Ca²⁺ uptake but had no effect on ATP-dependent Ca²⁺ uptake in the absence of taurine, indicating that taurine may be increasing ATP-dependent Ca²⁺ uptake through a mechanism of action involving the opening of cGMP-gated channels. The activation of cGMP-gated channels with dibutyryl-cGMP and with phosphodiesterase inhibition using zaprinast caused an increase in ATP-dependent Ca²⁺ uptake in isolated ROS, but not in taurine-stimulated ATP-dependent Ca²⁺ uptake. LY83583 had the same effects in isolated ROS as in retinal membrane preparations. Another inhibitor of cGMP-gated channels, Rp-8-Br-PET-cGMPS, produced the same pattern of inhibition in isolated ROS as LY83583. Thus, there appears to be a causal link between taurine and the activation of the cGMP-gated channels in the ROS under conditions of low calcium concentration, a connection that suggests an important role for taurine in the visual signalling function of the retina.     

红芽芋球茎片两步法离体快繁及其再生苗生理和光合特性研究

以江西铅山红芽芋(Colocasia esculenta L.Schott var.cormosus‘Hongyayu’)试管苗为材料,建立了芋球茎片两步法离体快繁体系,并对其再生苗的形态指标、染色体数目、生理和光合特性以及叶绿素荧光特性进行了检测。结果表明:(1)红芽芋球茎片单芽诱导的最佳培养基为MS+KT 2 mg/L+6-BA 1 mg/L+NAA0.1mg/L,诱导培养30d后将单芽从球茎片上分离,再接种到生根培养基(MS+KT 2mg/L+NAA 0.1mg/L)上培养30d即可形成完整植株,移栽成活率高达98%;(2)由球茎片单芽、丛生芽、不定芽离体快繁获得的红芽芋再生苗在形态指标、叶下表皮气孔参数、染色体数目、生理生化指标以及叶片光合特性参数和叶绿素荧光特性方面均无显著差异。说明红芽芋球茎片两步法离体培养的再生苗繁殖系数高、染色体数目稳定,该离体快繁体系可应用于江西铅山红芽芋的工厂化生产。     

Ontogenetic shifts in functional morphology of dragonfly legs (Odonata: Anisoptera)

Anisopteran leg functions change dramatically from the final larval stadium to the adult. Larvae use legs mainly for locomotion, walking, climbing, clinging, or burrowing. Adults use them for foraging and grasping mates, for perching, clinging to the vegetation, and for repelling rivals. In order to estimate the ontogenetic shift in the leg construction from the larva to the adult, this study quantitatively compared lengths of fore, mid, and hind legs and the relationships between three leg segments, femur, tibia, and tarsus, in larval and adult Anisoptera of the families Gomphidae, Aeshnidae, Cordulegastridae, Corduliidae, and Libellulidae, represented by two species each. We found that leg segment length ratio as well as ontogenetic shift in length ratios was different between families, but rather similar within the families. While little ontogenetic shift occurred in Aeshnidae, there were some modifications in Corduliidae and Libellulidae. The severest shift occurred in Gomphidae and Cordulegastridae, both having burrowing larvae. These two families form a cluster, which is in contrast to their taxonomic relationship within the Anisoptera. Cluster analysis implies that the function of larval legs is primarily responsible for grouping, whereas adult behavior or the taxonomic relationships do not explain the grouping. This result supports the previous hypothesis about the convergent functional shift of leg characters in the dragonfly ontogenesis.     

A Bayesian method to estimate the optimal threshold of a longitudinal biomarker

The objective of this study was to develop methods to estimate the optimal threshold of a longitudinal biomarker and its credible interval when the diagnostic test is based on a criterion that reflects a dynamic progression of that biomarker. Two methods are proposed: one parametric and one non‐parametric. In both the cases, the Bayesian inference was used to derive the posterior distribution of the optimal threshold from which an estimate and a credible interval could be obtained. A numerical study shows that the bias of the parametric method is low and the coverage probability of the credible interval close to the nominal value, with a small coverage asymmetry in some cases. This is also true for the non‐parametric method in case of large sample sizes. Both the methods were applied to estimate the optimal prostate‐specific antigen nadir value to diagnose prostate cancer recurrence after a high‐intensity focused ultrasound treatment. The parametric method can also be applied to non‐longitudinal biomarkers.     

Maternal investment in reproduction and its consequences in leatherback turtles

Maternal investment in reproduction by oviparous non-avian reptiles is usually limited to pre-ovipositional allocations to the number and size of eggs and clutches, thus making these species good subjects for testing hypotheses of reproductive optimality models. Because leatherback turtles (Dermochelys coriacea) stand out among oviparous amniotes by having the highest clutch frequency and producing the largest mass of eggs per reproductive season, we quantified maternal investment of 146 female leatherbacks over four nesting seasons (2001–2004) and found high inter- and intra-female variation in several reproductive characteristics. Estimated clutch frequency [coefficient of variation (CV) = 31%] and clutch size (CV = 26%) varied more among females than did egg mass (CV = 9%) and hatchling mass (CV = 7%). Moreover, clutch size had an approximately threefold higher effect on clutch mass than did egg mass. These results generally support predictions of reproductive optimality models in which species that lay several, large clutches per reproductive season should exhibit low variation in egg size and instead maximize egg number (clutch frequency and/or size). The number of hatchlings emerging per nest was positively correlated with clutch size, but fraction of eggs in a clutch yielding hatchlings (emergence success) was not correlated with clutch size and varied highly among females. In addition, seasonal fecundity and seasonal hatchling production increased with the frequency and the size of clutches (in order of effect size). Our results demonstrate that female leatherbacks exhibit high phenotypic variation in reproductive traits, possibly in response to environmental variability and/or resulting from genotypic variability within the population. Furthermore, high seasonal and lifetime fecundity of leatherbacks probably reflect compensation for high and unpredictable mortality during early life history stages in this species.     

Cancer immunotherapy, mathematical modeling and optimal control

Clinical immunologists, among other problems, routinely face a question: what is the best time and dose for a certain therapeutic agent to be administered to the patient in order to decrease/eradicate the pathological condition? In cancer immunotherapies the therapeutic agent is something able to elicit an immune response against cancer. The immune response has its own dynamics that depends on the immunogenicity of the therapeutic agent and on the duration of the immune response. The question then is "how can we decide when and how much of the drug to inject so to have a prolonged and effective immune response to the cancer?". This question can be addressed in mathematical terms in two stages: first one construct a mathematical model describing the cancer-immune interaction and secondly one applies the theory of optimal control to determine when and to which extent to stimulate the immune system by means of an immunotherapeutic agent administered in discrete variable doses within the therapeutic period. The solution of this mathematical problem is described and discussed in this article. We show that the method employed can be applied to find the optimal protocol in a variety of clinical problems where the kinetics of the drug or treatment and its influence on the physiologic/pathologic functions have been described by a system of ordinary differential equations.     

具空间扩散的时变种群系统的最优捕获控制

讨论了一类时变种群扩散系统的最优捕获控制的非线性问题,证明了最优捕获控制的存在性,并给出了控制u（t,x）∈Uad为最优的必要条件和最优性组．     

Application of the secondary structure model of rRNA for phylogeny: D2-D3 expansion segments of the LSU gene of plant-parasitic nematodes from the family Hoplolaimidae Filipjev, 1934

Knowledge of rRNA structure is increasingly important to assist phylogenetic analysis through reconstructing optimal alignment, utilizing molecule features as an additional source of data and refining appropriate models of evolution of the molecule. We describe a procedure of optimization for alignment and a new coding method for nucleotide sequence data using secondary structure models of the D2 and D3 expansion fragments of the LSU-rRNA gene reconstructed for fifteen nematode species of the agriculturally important and diverse family Hoplolaimidae, order Tylenchida. Using secondary structure information we converted the original sequence data into twenty-eight symbol codes and submitted the transformed data to maximum parsimony analysis. We also applied the original sequence data set for Bayesian inference. This used the doublet model with sixteen states of nucleotide doublets for the stem region and the standard model of DNA substitution with four nucleotide states for loops and bulges. By this approach, we demonstrate that using structural information for phylogenetic analyses led to trees with lower resolved relationships between clades and likely eliminated some artefactual support for misinterpreted relationships, such as paraphyly of Helicotylenchus or Rotylenchus. This study as well as future phylogenetic analyses is herein supported by the development of an on-line database, NEMrRNA, for rRNA molecules in a structural format for nematodes. We also have developed a new computer program, RNAstat, for calculation of nucleotide statistics designed and proposed for phylogenetic studies.