Biosynthesis of lipoic acid in the rat: Incorporation of 35S- and 14C-labeled precursors

After injection of various ³⁵S- and ¹⁴C-containing compounds, the incorporation of the label into the lipoic acid present in the liver of growing rats has been determined. The best precursor for sulfur atoms, after 24 h, is cysteine; methionine and cystamine are scarcely incorporated and thiosulfate not at all. Good precursors of the carbon moiety are acetate and octanoate, whereas the incorporation of butyrate and cysteine is very low. It is concluded that lipoic acid is biosynthesized in the rat liver, and that sulfur atoms probably originate from cysteine.     

Understanding Perceptions of Climate Change,Priorities, and Decision-Making among Municipalities in Lima,Peru to Better Inform Adaptation and Mitigation Planning

Climate change poses multiple risks to the population of Lima, the largest city and capital of Peru, located on the Pacific coast in a desert ecosystem. These risks include increased water scarcity, increased heat, and the introduction and emergence of vector-borne and other climate sensitive diseases. To respond to these threats, it is necessary for the government, at every level, to adopt more mitigation and adaptation strategies. Here, focus groups were conducted with representatives from five Lima municipalities to determine priorities, perception of climate change, and decision-making processes for implementing projects within each municipality. These factors can affect the ability and desire of a community to implement climate change adaptation and mitigation strategies. The results show that climate change and other environmental factors are of relatively low priority, whereas public safety and water and sanitation services are of highest concern. Perhaps most importantly, climate change is not well understood among the municipalities. Participants had trouble distinguishing climate change from other environmental issues and did not fully understand its causes and effects. Greater understanding of what climate change is and why it is important is necessary for it to become a priority for the municipalities. Different aspects of increased climate change awareness seem to be connected to having experienced extreme weather events, whether related or not to climate change, and to higher socioeconomic status.     

Effects of some indoor environmental factors on respiratory symptoms and lung function in a sample of young non smokers in North Italy

Summary We evaluated the effects of some indoor environmental factors in a non smoking subsample (n=381, age 8–19 years) of the general population living in the Po River Delta. Each subject completed an interviewer-administered standardized questionnaire on respiratory symptoms and risk factors. Acceptable maneuvers of forced vital capacity and slope of alveolar plateau of nitrogen were obtained in 96% and 59% of the subjects, respectively. In the houses there were more frequently natural gas for cooking (86%) than bottled gas (14%) and central heating (82%) than stove (18%). As regards passive smoking exposure, 18% of subjects had both parents smoking, 50% had one parent smoking. Significantly higher prevalence rates of wheeze, dyspnea, diagnosis of asthma were found in subjects of both sexes using bottled gas for cooking in comparison to those using natural gas, when also exposed to passive smoking. An insignificant trend towards higher symptom rates was shown by those using stove, instead of central heating. Lung function was affected only in females: those with both parents smoking had reduced forced expirograms, those with bottled gas for cooking or stove for heating had a decreased peak expiratory flow. Interactions of stove and passive smoking on peak expiratory flow and on slope of alveolar plateau were statistically significant. These findings confirm the mild adverse respiratory effects of certain home environment factors shown by other epidemiologic surveys in North Europe and in the USA. They have been a basis for the implementation, under the auspices of National Research Council and Electric Energy Authority, of future specific studies in which continuous monitoring of indoor pollutants and repeated recording of symptoms and lung function in North and Central Italy will be performed.     

Sialosignaling: Sialyltransferases as engines of self-fueling loops in cancer progression

Background

Glycosylation is increasingly recognized as one of the most relevant postranslational modifications. Sialic acids are negatively charged sugars which frequently terminate the carbohydrate chains of glycoproteins and glycolipids. The addition of sialic acids is mediated by sialyltransferases, a family of glycosyltransferases with a crucial role in cancer progression.

Scope of the review

To describe the phenotypic and clinical implications of altered expression of sialyltransferases and of their cognate sialylated structures in cancer. To propose a unifying model of the role of sialyltransferases and sialylated structures on cancer progression.

Major conclusions

We first discuss the biosynthesis and the role played by the major cancer-associated sialylated structures, including Thomsen–Friedenreich-associated antigens, sialyl Lewis antigens, α2,6-sialylated lactosamine, polysialic acid and gangliosides. Then, we show that altered sialyltransferase expression in cancer, consequence of genetic and epigenetic alterations, generates a flow of information toward the membrane through the biosynthesis of aberrantly sialylated molecules (inside-out signaling). In turn, the presence of aberrantly sialylated structures on cell membrane receptors generates a flow of information toward the nucleus, which can exacerbate the neoplastic phenotype (outside-in signaling). We provide examples of self-fueling loops generated by these flows of information.

General significance

Sialyltransferases have a wide impact on the biology of cancer and can be the target of innovative therapies. Our unified view provides a conceptual framework to understand the impact of altered glycosylation in cancer.     

Lipid-transfer proteins in biosynthetic pathways

Compartmentalization is a defining feature of eukaryotic cells that allows the spatial segregation of different functions, such as protein and lipid synthesis, and ensures their fidelity and efficiency. This imposes the need for an intense flux of metabolic intermediates between segregated enzymatic activities, as seen for the sequential transport of neosynthesized proteins through the segments of the secretory pathway during their post-translational modification. For lipid synthesis, the identification of proteins that transfer lipids between membranes has revealed an additional mechanism for this intercompartment exchange. The intense interest elicited by the lipid-transfer proteins over the last few years has led to the definition of their central role in key processes, such as lipid metabolism, membrane trafficking, and signaling.     

The crystal structure of a cockroach pheromone-binding protein suggests a new ligand binding and release mechanism

Pheromone-binding proteins (PBPs) are small helical proteins found in sensorial organs, particularly in the antennae, of moth and other insect species. They were proposed to solubilize and carry the hydrophobic pheromonal compounds through the antennal lymph to receptors, participating thus in the peri-receptor events of signal transduction. The x-ray structure of Bombyx mori PBP (BmorPBP), from male antennae, revealed a six-helix fold forming a cavity that contains the pheromone bombykol. We have identified a PBP (LmaPBP) from the cockroach Leucophaea maderae in the antennae of the females, the gender attracted by pheromones in this species. Here we report the crystal structure of LmaPBP alone or in complex with a fluorescent reporter (amino-naphthalen sulfonate, ANS) or with a component of the pheromonal blend, 3-hydroxy-butan-2-one. Both compounds bind in the internal cavity of LmaPBP, which is more hydrophilic than BmorPBP cavity. LmaPBP structure ends just after the sixth helix (helix F). BmorPBP structure extends beyond the sixth helix with a stretch of residues elongated at neutral pH and folding as a seventh internalized helix at low pH. These differences between LmaPBP and BmorPBP structures suggest that different binding and release mechanism may be adapted to the hydrophilicity or hydrophobicity of the pheromonal ligand.     

The role of the social sciences and economics in understanding and informing tree biosecurity policy and planning: a global summary and synthesis

Increased global biosecurity threats to trees, woods and forests have been strongly linked to the upsurge in worldwide trade and the expansion of tourism. A whole range of social, economic and political actors are implicated and affected by the movement of pests and diseases along these international pathways. A number of factors affect the actions of stakeholders, and wider public, including their values and motivations, how risks are perceived and acted upon, their ability to act, as well as the existing regulatory and economic environment. Understanding these factors is key to any future attempts to improve biosecurity policy and practice, and we present available evidence on six key dimension: (1) the role of different stakeholders and the broader public within tree health; (2) levels of knowledge and awareness of tree pests and diseases amongst the variety of end-user ‘stakeholder’ groups, and influences on their attitudes and practices; (3) social acceptability of management approaches; (4) the impact of formal and informal governance arrangements; (5) risk communication; (6) economic analyses on the impact of tree pests. We conclude by identifying evidence gaps and emphasising the need for better integration within the social sciences and between the social and natural sciences to promote effective interdisciplinary and policy-relevant contributions to tree health.     

The CD5+ B-cell

In the last two decades, many efforts have been made to better understand the biology of B-lymphoproliferative disorders through the knowledge of physiology and function of the postulated normal counterpart. The follicular mantle B-cells express a typical CD23+ IgM+ IgD+ phenotype and surround the germinal center area in secondary lymphoid organs. CD5+ B-cells with FM phenotype can be isolated from different sources and all share similar morphologic, phenotypic and functional features (small cells, scanty nucleus/cytoplasm ratio, unmutated VH genes, response to polyclonal activators but not to T independent antigens, production of "natural" antibodies). While the CD5+ B-cells predominate in fetal life, their number decreases with age. However, the CD5+ B-cells have been demonstrated to increase again in elderly both in man and mouse. This finding may explain the incidence of B-CLL and of MCL that are believed to represent the malignant transformation of the normal CD5+ B-cells, among elderly and middle aged individuals, respectively.