Recent progress in understanding glutaric acidemias

Glutaric acidemia, which is due to inherited deficiency of glutaryl-CoA dehydrogenase, is characterized clinically by progressive dystonia and dyskinesia in childhood, and pathologically by degeneration of the caudate and putamen. Results using newer imaging techniques (computer tomography and magnetic resonance image scanning) suggest that neurological involvement in this condition begins before birth, and that gliosis of the basal ganglia is a relatively late event. Glutaric acidemia type II is usually due to inherited deficiency of electron transfer flavoprotein (ETF) or ETF:ubiquinone oxidoreductase, but some patients with typical disease may have another, to date undefined, abnormality. There may also be a clinical phenotype of glutaric acidemia type II which, like glutaryl-CoA dehydrogenase deficiency, is characterized by a movement disorder and by degeneration of the basal ganglia.     

Recent progress towards understanding the synaptic ribbon

Neurons of the visual, auditory and vestibular systems that signal through graded changes in membrane potential rely upon synaptic ribbons for the exquisite control of neurotransmitter release. Although clearly important for tonic neurotransmission, the precise role of synaptic ribbons remains elusive. In recent years, several genetic, biochemical, electrophysiological and optical approaches have begun to shed light on the functions of these enigmatic organelles.     

Recent progress in understanding larval dispersal: new directions and digressions

Larvae have been difficult to study because their small sizelimits our ability to understand their behavior and the conditionsthey experience. Questions about larval transport focus largelyon (a) where they go [dispersal] and (b) where they come from[connectivity]. Mechanisms of transport have been intensivelystudied in recent decades. As our ability to identify larvalsources develops, the consequences of connectivity are garneringmore consideration. Attention to transport and connectivityissues has increased dramatically in the past decade, fueledby changing motivations that now include management of fisheriesresources, understanding of the spread of invasive species,conservation through the design of marine reserves, and predictionof climate-change effects. Current progress involves both technologicaladvances and the integration of disciplines and approaches.This review focuses on insights gained from physical modeling,chemical tracking, and genetic approaches. I consider how newfindings are motivating paradigm shifts concerning (1) life-historyconsequences; (2) the openness of marine populations, self-recruitment,and population connectivity; (3) the role of behavior; and (4)the significance of variability in space and time. A challengefor the future will be to integrate methods that address dispersalon short (intragenerational) timescales such as elemental fingerprintingand numerical simulations with those that reflect longer timescalessuch as gene flow estimates and demographic modeling. Recognitionand treatment of the continuum between ecological and evolutionarytimescales will be necessary to advance the mechanistic understandingof larval and population dynamics.     

Recent progress in understanding the evolution of carnivorous lentibulariaceae (lamiales)

Carnivorous plants have emerged as model systems for addressing many ecological and evolutionary questions, and since Lentibulariaceae comprise more than half of all known carnivorous species (325 spp.), they are of particular interest. Studies using various molecular markers have established that Lentibulariaceae and their three genera are monophyletic with Pinguicula being sister to a Genlisea-Utricularia-clade, while the closest relatives of the family remain uncertain. Character states of the carnivorous syndrome in related proto-carnivorous lamialean families apparently emerged independently. In Utricularia, the terrestrial habit has been reconstructed as plesiomorphic, and an extension of subgenus Polypompholyx is warranted. In the protozoan-attracting Genlisea, subgenus Tayloria is revealed as basal lineage. In Pinguicula, the six major lineages found reflect radiations in clearly defined geographic regions, whereas most previously recognized subgeneric taxa are non-monophyletic. Genlisea and Utricularia exhibit substitutional rates that rank among the highest in angiosperms for the molecular markers analyzed. One possible explanation for this lies in selective constraints on a wide range of genomic regions that may have been lowered due to the use of an alternative mode of acquiring nutrients.     

Recent progress in understanding thiamin biosynthesis and its genetic regulation in Saccharomyces cerevisiae

The yeast Saccharomyces cerevisiae is able to synthesize thiamin pyrophosphate (TPP) de novo, which involves the independent formation of two ring structures, 2-methyl-4-amino-5-hydroxymethylpyrimidine and 4-methyl-5-β-hydroxyethylthiazole, in the early steps. In addition, this organism can efficiently utilize thiamin from the extracellular environment to produce TPP. Nineteen genes involved in the synthesis of TPP and the utilization of thiamin (THI genes) have been identified, and the function of several THI genes has been elucidated. All THI genes participating in the synthesis of the pyrimidine unit belong to multigene families. It is also intriguing that some thiamin biosynthetic proteins are composed of two distinct domains or form an enzyme complex. The expression of THI genes is coordinately induced in response to thiamin starvation. It is likely that the induction of THI genes is activated by a positive regulatory factor complex and that the protein–protein interaction among the factors is disturbed by TPP. Thiamin-hyperproducing yeast and fermented food containing a high content of thiamin are expected to be available in the future based on the progress in understanding thiamin biosynthesis and its genetic regulation in S. cerevisiae.     

Bartonella-induced endothelial cell proliferation is mediated by release of calcium from intracellular stores

The facultative intracellular bacterium Bartonella henselae induces unique angiogenic lesions in immunocompromised hosts. To determine the role of intracellular calcium pools in B. henselae-induced endothelial cell proliferation, we generated B. henselae-conditioned medium (BCM) and tested the ability of these cell-free proteins to induce human umbilical vein endothelial cell (HUVEC) proliferation, CXCL8 production, and intracellular Ca2+ signals. HUVECs incubated with BCM for 3 days had higher cell numbers than controls. In addition, HUVECs produced increased amounts of CXCL8 in response to BCM when compared to medium controls. When BCM was added to HUVECs and the intracellular Ca2+ response measured with the calcium-sensitive dye fura-2/AM, a Ca2+ rise was demonstrated. It was determined that this Ca2+ rise originated from intracellular Ca2+ stores through the use of the Ca2+ ATPase inhibitor thapsigargin. Further, it was demonstrated that BCM enhanced CXCL8 production and HUVEC proliferation in a Ca2+-dependent manner. Conditioned medium from B. henselae causes an intracellular Ca2+ rise in HUVECs, which is involved in B. henselae-induced HUVEC proliferation and CXCL8 production. These results implicate intracellular Ca2+ pools in B. henselae-induced angiogenesis and may lead to increased understanding of the mechanisms of pathogen-induced angiogenesis.     

Recent advances in understanding endogenous fibrinolysis: implications for molecular-based treatment of vascular disorders

The fate of a forming thrombus is determined through the delicate balance between the coagulation cascade, favouring clot formation, and the fibrinolytic system, favouring clot lysis. These processes occur simultaneously, and enhancement of fibrinolysis has been shown to reduce occlusive thrombus formation in animal models. This review examines the roles of the major fibrinolytic factors involved in clot lysis. The regulation of plasmin activity by plasminogen activators, alpha-2-antiplasmin, plasminogen activator inhibitor 1, and thrombin-activatable fibrinolysis inhibitor, and their effects on thrombus formation in vivo are discussed. Since alterations in fibrinolytic capacity appear to affect thrombus formation in animal models, there is considerable interest in the pharmacological manipulation of fibrinolysis.     

Transthyretin and familial amyloidotic polyneuropathy. Recent progress in understanding the molecular mechanism of neurodegeneration

Familial amyloidotic polyneuropathy (FAP) is an inherited autosomal dominant disease that is commonly caused by accumulation of deposits of transthyretin (TTR) amyloid around peripheral nerves. The only effective treatment for FAP is liver transplantation. However, recent studies on TTR aggregation provide clues to the mechanism of the molecular pathogenesis of FAP and suggest new avenues for therapeutic intervention. It is increasingly recognized that there are common features of a number of protein-misfolding diseases that can lead to neurodegeneration. As for other amyloidogenic proteins, the most toxic forms of aggregated TTR are likely to be the low-molecular-mass diffusible species, and there is increasing evidence that this toxicity is mediated by disturbances in calcium homeostasis. This article reviews what is already known about the mechanism of TTR aggregation in FAP and describes how recent discoveries in other areas of amyloid research, particularly Alzheimer's disease, provide clues to the molecular pathogenesis of FAP.     

Recent progress in the understanding of tissue culture-induced genome level changes in plants and potential applications

In vitro cell and tissue-based systems have tremendous potential in fundamental research and for commercial applications such as clonal propagation, genetic engineering and production of valuable metabolites. Since the invention of plant cell and tissue culture techniques more than half a century ago, scientists have been trying to understand the morphological, physiological, biochemical and molecular changes associated with tissue culture responses. Establishment of de novo developmental cell fate in vitro is governed by factors such as genetic make-up, stress and plant growth regulators. In vitro culture is believed to destabilize the genetic and epigenetic program of intact plant tissue and can lead to chromosomal and DNA sequence variations, methylation changes, transposon activation, and generation of somaclonal variants. In this review, we discuss the current status of understanding the genomic and epigenomic changes that take place under in vitro conditions. It is hoped that a precise and comprehensive knowledge of the molecular basis of these variations and acquisition of developmental cell fate would help to devise strategies to improve the totipotency and embryogenic capability in recalcitrant species and genotypes, and to address bottlenecks associated with clonal propagation.     

抵抗素的研究进展

抵抗素(resistin)是近年来发现的一个新脂肪细胞因子,最初在动物实验被用于联系肥胖、胰岛素抵抗和2型糖尿病.但随着进一步在人类实验的研究中发现,抵抗素能调节炎症反应而非胰岛素敏感性,研究发现抵抗素能促进炎症发生,炎症因子也能调节抵抗素的表达.动脉硬化是一种慢性亚临床性炎症,大量的体外研究提示抵抗素有可能作为一种促炎因子,通过激活内皮功能,诱导平滑肌增殖迁移,促巨噬细胞的脂质沉积,导致脂质代谢紊乱等途径,促进动脉粥样硬化的发生与发展.     

Recent progress in histochemistry

The progress in discerning the structure and function of cells and tissues in health and disease has been achieved to a large extent by the continued development of new reagents for histochemistry, the improvement of existing techniques and new imaging techniques. This review will highlight some advancements made in these fields.