8-Hydroxypegolettiolide,a sesquiterpene lactone with a new carbon skeleton and further constituents from Pegolettia senegalensis

The investigation of Pegolettia senegalensis afforded several new sesquiterpene lactones, eight cis-6,12-germacra-trans,trans-1(10),4,11-trienolides, five cis-6,12-eudesmanolides, two elemanolides, 8,14-cyclogermacra-1(10),4,7(11)-trien-6,12-olide with a new carbon skeleton, three germacra-1(10),4,11(13)-trien-12-oic acids with ester residues at C-8, 18-hydroxygeranyl nerol, 1,3-dihydroxyoctadecane and a mixture of esters of 3,4-dihydroxy-dihydrocinnamyl alcohol. The structures were elucidated by high field ¹HNMR spectroscopy and some chemical transformations. The C-10 configuration of 6,12-cis-eudesmanolides from Calostephane divaricata and Inula crithmoides most likely has to be corrected. The chemotaxonomic situation of the genus Pegolettia and biogenetic considerations are discussed briefly.     

Genetic polymorphism of serotonin transporter 5-HTTLPR: involvement in smoking behaviour

Data suggest that the serotonin (5-hydroxytryptamine, 5-HT) system is implicated in the pathogenesis of multiple neuropsychiatric disorders and may also be involved in smoking behaviour since nicotine increases brain serotonin secretion. It is known that smoking behaviour is influenced by both genetic and environmental factors. The present review examines the role of the serotonin transporter gene (5-HTT) in smoking behaviour and investigating studies that showed association of 5-HTT gene with smoking. This study discusses a polymorphism which has been investigated by many researchers, as the bi-allelic insertion/deletion polymorphism in the 5^′- flanking promoter region (5-HTTLPR). This gene has received considerable attention in attempts to understand the molecular determinants of smoking. Therefore, in the present study, the relationship between genetic polymorphism of serotonin transporter in smoking behaviour is reviewed considering the interactive effect of genetic factors.     

Tailoring Proteins to Re-Evolve Nature: A Short Review

Proteins are key biomolecules for most biological processes, their function is related to their conformation that is also dictated by their sequence of amino acids. Through evolution, nature has produced an immense variety of enzymatic tools of high efficiency and selectivity, and thanks to the understanding of the molecular basis of life and the technological advances, scientists have learned to introduce mutations and select mutant enzymes, to optimize and control their molecular fitness characteristics mainly for industrial, medical and environmental applications. The relationship between protein structure and enzymatic functionality is essential, and there are various experimental and instrumental techniques for unravelling the molecular changes, activities and specificities. Protein engineering applies computational tools, in hand with experimental tools for mutations, like directed evolution and rational design, along with screening methods to obtain protein variations with the desired properties under a short time frame. With innovations in technology, it is possible to fine tune properties in proteins and reach new frontiers in their applications. The present review will briefly discuss these points and methods, with a glimpse on their strengths and pitfalls, while giving an overview of the versatility of synthetic proteins and their huge potential for biotechnological and biomedical fields.     

Cancer genes hypermethylated in human embryonic stem cells

Developmental genes are silenced in embryonic stem cells by a bivalent histone-based chromatin mark. It has been proposed that this mark also confers a predisposition to aberrant DNA promoter hypermethylation of tumor suppressor genes (TSGs) in cancer. We report here that silencing of a significant proportion of these TSGs in human embryonic and adult stem cells is associated with promoter DNA hypermethylation. Our results indicate a role for DNA methylation in the control of gene expression in human stem cells and suggest that, for genes repressed by promoter hypermethylation in stem cells in vivo, the aberrant process in cancer could be understood as a defect in establishing an unmethylated promoter during differentiation, rather than as an anomalous process of de novo hypermethylation.     

New lead elements for histamine H3 receptor ligands in the pyrrolo[2,3-d]pyrimidine class

This work describes the microwave assisted synthesis of twelve novel histamine H₃ receptor ligands. They display pyrrolo[2,3-d]pyrimidine derivatives with rigidized aliphatic amines as warheads. The compounds were screened for H₃R and H₄R binding affinities in radioligand displacement assays and the most potent compounds were evaluated for H₃R binding properties in vitro and in docking studies. The combination of a rigidized H₃R warhead and the pyrrolo[2,3-d]pyrimidine scaffold resulted in selective activity at the H₃ receptor with a pK_i value of 6.90 for the most potent compound. A bipiperidine warhead displayed higher affinity than a piperazine or morpholine motif, while a naphthyl moiety in the arbitrary region increased affinity compared to a phenyl derivative. The compounds can be starting points for novel, simply synthesized histamine H₃ receptor ligands.     

Regulation of autophagy as a therapy for immunosenescence-driven cancer and neurodegenerative diseases: The role of exercise

Aging is one of the risk factors for the development of low-grade inflammation morbidities, such as several types of cancer and neurodegenerative diseases, due to changes in the metabolism, hormonal secretion, and immunosenescence. The senescence of the immune system leads to improper control of infections and tissue damage increasing age-related diseases. One of the mechanisms that maintain cellular homeostasis is autophagy, a cell-survival mechanism, and it has been proposed as one of the most powerful antiaging therapies. Regular exercise can reestablish autophagy, probably through AMP-activated protein kinase activation, and help in reducing the age-related senescence diseases. Therefore, in this study, we discuss the effects of exercise training in immunosenescence and autophagy, preventing the two main age-related disease, cancer and neurodegeneration.     

IMMUNOLOGICAL STUDIES OF THE RAT OLFACTORY MARKER PROTEIN1

Abstract— Antisera against the rat olfactory marker protein were prepared by injection of the homogeneous protein into a goat and a rabbit. When the antisera were tested by immunodiffusion against olfactory tissue extracts, many but not all mammalian species cross-reacted against these antisera. Immunoprecipitin titrations with the goat antiserum generally showed higher cross-reactivity against olfactory extracts from species more closely related to the rat. Human olfactory bulb extracts and non-mammalian olfactory tissue extracts did not cross-react with the antisera by either immunodiffusion tests or immunoprecipitin titrations, however, they did cross-react when tested by a competitive binding radioimmunoassay using tritium-labelled purified rat protein and the goat antibody. The olfactory marker protein which is an example of a brain protein specific to one cell, the olfactory chemoreceptor neuron, has a very wide species distribution, being present in rat, mouse, hamster, guinea-pig, sheep, cow, rabbit, pig, dog, man, frog and garfish. Therefore it presumably plays an important and unique role related to the function of this primary chemosensory neuron.     

Genetic mapping and QTL analysis in European hazelnut (<Emphasis Type="Italic">Corylus avellana</Emphasis> L.)

The European hazelnut (Corylus avellana L.) is the most economically important nut species in the Betulaceae family. Despite the need for new improved hazelnut cultivars, few breeding programs are carried out because of the large plant size, the long lifecycle of the plant, and the expense and time required. To date, there are no reports of maps with quantitative trait loci (QTL) in hazelnut. Our objective in the present study was to identify QTL associated with vegetative traits to allow marker-assisted selection (MAS). An F1 progeny (275 plants) of Tonda Gentile delle Langhe × Merveille de Bollwiller obtained in 2009 was used to develop a QTL linkage map for vigour, sucker habit, and time of bud burst, after three years of observations. A set of 163 plants were analysed with 152 microsatellite markers. A map of 11 linkage groups was obtained, covering 663.1 cM, and 15 QTLs were identified and mapped for the traits examined. Of them, 10 were ‘major’ QTL, including a stably expressed region on LG_02 for leaf bud burst. At least one major QTL for each year underlies the variation in each trait and a clustering of QTL for trunk circumference and suckers/trunk circumference ratio with high inter-trait correlations was observed on LG_05, suggesting a single pleiotropic locus. This research represents an initial step in the future identification of chromosomal regions carrying genes of interest, important for breeding programs and MAS.     

Cytotoxic T-Lymphocyte Epitope Immunodominance in the Control of Choroid Plexus Tumors in Simian Virus 40 Large T Antigen Transgenic Mice

The simian virus 40 (SV40) large tumor antigen (Tag) is a virus-encoded oncoprotein which is the target of a strong cytotoxic T-lymphocyte (CTL) response. Three immunodominant H-2(b)-restricted epitopes, designated epitopes I, II/III, and IV, have been defined. We investigated whether induction of CTLs directed against these Tag epitopes might control Tag-induced tumors in SV11(+) (H-2(b)) mice. SV11(+) mice develop spontaneous tumors of the choroid plexus due to expression of SV40 Tag as a transgene. We demonstrate that SV11(+) mice are functionally tolerant to the immunodominant Tag CTL epitopes. CTLs specific for the H-2Kb-restricted Tag epitope IV were induced in SV11(+) mice following adoptive transfer with unprimed C57BL/6 spleen cells and immunization with recombinant vaccinia viruses expressing either full-length Tag or the H-2Kb-restricted epitope IV as a minigene. In addition, irradiation of SV11(+) mice prior to adoptive transfer with unprimed C57BL/6 spleen cells led to the priming of epitope IV-specific CTLs by the endogenous Tag. Induction of epitope IV-specific CTLs in SV11(+) mice by either approach correlated with increased life span and control of the choroid plexus tumor progression, indicating that CTLs specific for the immunodominant Tag epitope IV control the progressive growth of spontaneous tumors induced by this DNA virus oncogene in transgenic mice.