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Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (statins) are the most effective and best-tolerated drugs to treat elevated levels of low-density lipoprotein cholesterol (LDL-C). In addition, they exhibit other effects unrelated to their lipid lowering effects (pleiotropic actions). In recent years, experimental and clinical evidence demonstrates that statins exert antiarrhythmic properties, reducing the recurrences of supraventricular and life-threatening ventricular arrhythmias both in patients with and without coronary artery disease (CAD). Thus, statins may constitute a novel therapeutic approach to cardiac arrhythmias. This article reviews the antiarrhythmic properties of statins as well as the possible mechanisms involved, including the lowering of LDL-C levels, the improvement of endothelial dysfunction and autonomic function, the stabilization of the atherosclerotic plaques, the antioxidant, antiinflammatory, antithrombotic and cardioprotective properties and the modulation of transmembrane ion fluxes., CICYT, Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, Red HERACLES, Mutua Madrileña, Depto. de Farmacología y Toxicología, Fac. de Medicina, TRUE, pub

Influenza vaccines are designed to mimic natural influenza virus exposure and stimulate a long-lasting immune response to future infections. The evolving nature of the influenza virus makes vaccination an important and efficacious strategy to reduce healthcare-related complications of influenza. Several lines of evidence indicate that influenza vaccination may induce nonspecific effects, also referred to as heterologous or pleiotropic effects, that go beyond protection against infection. Different explanations are proposed, including the upregulation and downregulation of cytokines and epigenetic reprogramming in monocytes and natural killer cells, imprinting an immunological memory in the innate immune system, a phenomenon termed "trained immunity". Also, cross-reactivity between related stimuli and bystander activation, which entails activation of B and T lymphocytes without specific recognition of antigens, may play a role. In this review, we will discuss the possible nonspecific effects of influenza vaccination in cardiovascular disease, type 1 diabetes, cancer, and Alzheimer's disease, future research questions, and potential implications. A discussion of the potential effects on infections by other pathogens is beyond the scope of this review.

Considering the urgent need for novel therapeutics in ongoing COVID-19 pandemic, drug repurposing approach might offer rapid solutions comparing to de novo drug design. In this study, we designed an integrative in silico drug repurposing approach for rapid selection of potential candidates against SARS-CoV-2 Main Protease (Mpro). To screen FDA-approved drugs, we implemented structure-based molecular modelling techniques, physiologically-based pharmacokinetic (PBPK) modelling of drugs disposition and data mining analysis of drug-gene-COVID-19 association. Through presented approach, we selected the most promising FDA approved drugs for further COVID-19 drug development campaigns and analysed them in context of available experimental data. To the best of our knowledge, this is unique in silico study which integrates structure-based molecular modeling of Mpro inhibitors with predictions of their tissue disposition, drug-gene-COVID-19 associations and prediction of pleiotropic effects of selected candidates.

This editorial presents three comprehensive reviews of recent preclinical and clinical findings supporting the healing of critical bone defects through adjuvant therapy approaches, which have been published in a special issue. In summary, these articles highlight current concepts that attempt to improve osteogenesis and bone healing using small molecule drugs and intelligent drug delivery methods. The main conclusions lead to an evaluation of the modulation of angiogenesis and microcirculation as a very promising concept. The modulation of inflammation, on the other hand, was evaluated as critical with respect to the start and duration of therapy. Novel solutions are expected from a targeted modulation of bone metabolism, the use of bifunctional or hybrid compounds, appropriate drug combinations and delivery systems.

Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are the largest selling class of drugs prescribed for the pharmacological treatment of hypercholesterolemia and dyslipidaemia. Statins also possess other therapeutic effects, called pleiotropic, because the blockade of the conversion of HMG-CoA to (R)-mevalonate produces a concomitant inhibition of the biosynthesis of numerous isoprenoid metabolites (e.g., geranylgeranyl pyrophosphate (GGPP) or farnesyl pyrophosphate (FPP)). Thus, the prenylation of several cell signalling proteins (small GTPase family members: Ras, Rac, and Rho) is hampered, so that these molecular switches, controlling multiple pathways and cell functions (maintenance of cell shape, motility, factor secretion, differentiation, and proliferation) are regulated, leading to beneficial effects in cardiovascular health, regulation of the immune system, anti-inflammatory and immunosuppressive properties, prevention and treatment of sepsis, treatment of autoimmune diseases, osteoporosis, kidney and neurological disorders, or even in cancer therapy. Thus, there is a growing interest in developing more sustainable protocols for preparation of statins, and the introduction of biocatalyzed steps into the synthetic pathways is highly advantageous—synthetic routes are conducted under mild reaction conditions, at ambient temperature, and can use water as a reaction medium in many cases. Furthermore, their high selectivity avoids the need for functional group activation and protection/deprotection steps usually required in traditional organic synthesis. Therefore, biocatalysis provides shorter processes, produces less waste, and reduces manufacturing costs and environmental impact. In this review, we will comment on the pleiotropic effects of statins and will illustrate some biotransformations nowadays implemented for statin synthesis., Ministerio de Economía, Comercio y Empresa (España), Depto. de Química en Ciencias Farmacéuticas, Fac. de Farmacia, TRUE, pub

Erythropoiesis is triggered by hypoxia and is strictly regulated by hormones, growth factors, cytokines, and vitamins to ensure an adequate oxygen delivery to all body cells. Abnormalities in one or more of these factors may induce different kinds of anemia requiring different treatments. A key player in red blood cell production is erythropoietin. It is a glycoprotein hormone, mainly produced by the kidneys, that promotes erythroid progenitor cell survival and differentiation in the bone marrow and regulates iron metabolism. A deficit in erythropoietin synthesis is the main cause of the normochromic normocytic anemia frequently observed in patients with progressive chronic kidney disease. The present review summarizes the most recent findings about each step of the erythropoietic process, going from the renal oxygen sensing system to the cascade of events induced by erythropoietin through its own receptor in the bone marrow. The paper also describes the new class of drugs designed to stabilize the hypoxia-inducible factor by inhibiting prolyl hydroxylase, with a discussion about their metabolism, disposition, efficacy, and safety. According to many trials, these drugs seem able to simulate tissue hypoxia and then stimulate erythropoiesis in patients affected by renal impairment. In conclusion, the in-depth investigation of all events involved in erythropoiesis is crucial to understand anemia pathophysiology and to identify new therapeutic strategies, in an attempt to overcome the potential side effects of the commonly used erythropoiesis-stimulating agents.

Previously, we showed that transplastomic tobacco plants expressing the LiHsp83-SAG1 fusion protein displayed a chlorotic phenotype and growth retardation, while plants expressing the SAG1 and GRA4 antigens alone did not. We conducted a comprehensive examination of the metabolic and photosynthetic parameters that could be affecting the normal growth of LiHsp83-SAG1 plants in order to understand the origin of these pleiotropic effects. These plants presented all photosynthetic pigments and parameters related to PSII efficiency significantly diminished. However, the expression of CHLI, RSSU and LHCa/b genes did not show significant differences between LiHsp83-SAG1 and control plants. Total protein, starch, and soluble sugar contents were also greatly reduced in LiHsp83-SAG1 plants. Since Hsp90 s are constitutively expressed at much higher concentrations at high temperatures, we tested if the fitness of LiHsp83-SAG1 over-expressing LiHsp83 would improve after heat treatment. LiHsp83-SAG1 plants showed an important alleviation of their phenotype and an evident recovery of the PSII function. As far as we know, this is the first report where it is demonstrated that a transplastomic line performs much better at higher temperatures. Finally, we detected that LiHsp83-SAG1 protein could be binding to key photosynthesis-related proteins at 37 °C. Our results suggest that the excess of this molecular chaperone could benefit the plant in a possible heat shock and prevent the expected denaturation of proteins. However, the LiHsp83-SAG1 protein content was weakly decreased in heat-treated plants. Therefore, we cannot rule out that the alleviation observed at 37 °C may be partially due to a reduction of the levels of the recombinant protein.

Introduction: A step-up strategy for dipeptidyl peptidase (DPP)-4 inhibitor-based regimens has not yet been established. In addition, similarities and differences between DPP-4 inhibitors and glucagon-like peptide (GLP)-1 receptor agonists remain to be elucidated in humans. We investigated the pleiotropic effects of vildagliptin vs liraglutide in patients with type 2 diabetes on sitagliptin-based regimens in an open-label, randomized, clinical trial. Materials and Methods: A total of 122 patients with type 2 diabetes that was inadequately controlled by sitagliptin-based regimens were randomly assigned to either vildagliptin (50 mg, twice daily) or liraglutide treatment (0.9 mg, once daily) for 12 weeks. The primary outcomes were glycated hemoglobin and body mass index. Results: Both vildagliptin and liraglutide significantly lowered glycated hemoglobin within 12 weeks after switching from sitagliptin, but liraglutide produced a greater reduction (-0.67 ± 0.12% vs -0.36 ± 0.53%). Liraglutide lowered body mass index, whereas vildagliptin did not affect body mass index. Vildagliptin lowered fasting C-peptide immunoreactivity, but liraglutide did not. Vildagliptin increased serum levels of adiponectin, arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid, whereas liraglutide had no effect on these levels. Quality of life, assessed using the diabetes treatment satisfaction questionnaire, was not impaired in either group. The most common adverse events were gastrointestinal symptoms, which occurred with similar frequencies in both groups. Conclusions: Vildagliptin-mediated improvements in glycemic control did not correlate with indices for insulin secretion and insulin sensitivity. Switching from sitagliptin to liraglutide is useful in managing hyperglycemia and weight. Each agent exerts unique pleiotropic effects. This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (no. 000004953). © 2014 The Authors. Jo

In the family of chlorophyll binding proteins, single helix small CAB-like proteins (SCPs) are found in all organisms performing oxygenic photosynthesis. Here, we investigated the function of these stress-inducible proteins in the cyanobacterium Synechocystis sp. PCC 6803. We compared physiological, proteome and transcriptome traits of a Photosystem I (PSI) deletion strain, which constitutively induces SCPs, and a PSI-less/ScpABCDE− without SCPs. The SCP mutant cells were larger in size, showed irregular thylakoid structure and differed in cell-surface morphology. Deletion of scp genes strongly affected the carbon (C) and nitrogen (N) balance, resulting in accumulation of carbohydrates and a decrease in N-rich compounds (proteins and chlorophyll). Data from transcriptomic and metabolomic experiments revealed a role of SCPs in the control of chlorophyll biosynthesis. Additionally, SCPs diminished formation of reactive oxygen species, thereby preventing damage within Photosystem II. We conclude that the lack of SCP-function to remove free chlorophyll under stress conditions has a large impact on the metabolism of the entire cell.

Vitamin D deficiency is highly prevalent in peritoneal dialysis (PD) patients. The administration of active vitamin D, or vitamin D analogs, in PD may have significant pleiotropic effects. Specifically, the improvement of the bactericidal response could decrease the risk of peritonitis, the antiproteinuric effect could preserve the residual renal function, the reduction of the peritoneal protein loss could decrease the risk of malnutrition, and the antifibrotic effect could reduce the risk of sclerosing encapsulating peritonitis., Il deficit di vitamina D è molto frequente nei pazienti in dialisi peritoneale (PD). La somministrazione di vitamina D attiva o di analoghi potrebbe avere degli effetti pleiotropici significativi nei pazienti in PD. In particolare, un potenziamento dell'attività battericida potrebbe ridurre il rischio di peritonite, l'effetto antiproteinurico potrebbe mantenere la funzione renale residua, la riduzione della perdita proteica peritoneale potrebbe ridurre il rischio di malnutrizione e l'effetto antifibrotico potrebbe ridurre il rischio di peritonite sclerosante incapsulante.

Vitamin D deficiency is highly prevalent in peritoneal dialysis (PD) patients. The administration of active vitamin D, or vitamin D analogs, in PD may have significant pleiotropic effects. Specifically, the improvement of the bactericidal response could decrease the risk of peritonitis, the antiproteinuric effect could preserve the residual renal function, the reduction of the peritoneal protein loss could decrease the risk of malnutrition, and the antifibrotic effect could reduce the risk of sclerosing encapsulating peritonitis., Il deficit di vitamina D è molto frequente nei pazienti in dialisi peritoneale (PD). La somministrazione di vitamina D attiva o di analoghi potrebbe avere degli effetti pleiotropici significativi nei pazienti in PD. In particolare, un potenziamento dell'attività battericida potrebbe ridurre il rischio di peritonite, l'effetto antiproteinurico potrebbe mantenere la funzione renale residua, la riduzione della perdita proteica peritoneale potrebbe ridurre il rischio di malnutrizione e l'effetto antifibrotico potrebbe ridurre il rischio di peritonite sclerosante incapsulante.

Vitamin D deficiency is highly prevalent in peritoneal dialysis (PD) patients. The administration of active vitamin D, or vitamin D analogs, in PD may have significant pleiotropic effects. Specifically, the improvement of the bactericidal response could decrease the risk of peritonitis, the antiproteinuric effect could preserve the residual renal function, the reduction of the peritoneal protein loss could decrease the risk of malnutrition, and the antifibrotic effect could reduce the risk of sclerosing encapsulating peritonitis., Il deficit di vitamina D è molto frequente nei pazienti in dialisi peritoneale (PD). La somministrazione di vitamina D attiva o di analoghi potrebbe avere degli effetti pleiotropici significativi nei pazienti in PD. In particolare, un potenziamento dell'attività battericida potrebbe ridurre il rischio di peritonite, l'effetto antiproteinurico potrebbe mantenere la funzione renale residua, la riduzione della perdita proteica peritoneale potrebbe ridurre il rischio di malnutrizione e l'effetto antifibrotico potrebbe ridurre il rischio di peritonite sclerosante incapsulante.

[EN] Background: Porcine fatty acid composition is a key factor for quality and nutritive value of pork. Several QTLs for fatty acid composition have been reported in diverse fat tissues. The results obtained so far seem to point out different genetic control of fatty acid composition conditional on the fat deposits. Those studies have been conducted using simple approaches and most of them focused on one single tissue. The first objective of the present study was to identify tissue-specific and tissue-consistent QTLs for fatty acid composition in backfat and intramuscular fat, combining linkage mapping and GWAS approaches and conducted under single and multitrait models. A second aim was to identify powerful candidate genes for these tissue-consistent QTLs, using microarray gene expression data and following a targeted genetical genomics approach. Results: The single model analyses, linkage and GWAS, revealed over 30 and 20 chromosomal regions, 24 of them identified here for the first time, specifically associated to the content of diverse fatty acids in BF and IMF, respectively. The analyses with multitrait models allowed identifying for the first time with a formal statistical approach seven different regions with pleiotropic effects on particular fatty acids in both fat deposits. The most relevant were found on SSC8 for C16:0 and C16:1(n-7) fatty acids, detected by both linkage and GWAS approaches. Other detected pleiotropic regions included one on SSC1 for C16:0, two on SSC4 for C16:0 and C18:2, one on SSC11 for C20:3 and the last one on SSC17 for C16:0. Finally, a targeted eQTL scan focused on regions showing tissue consistent effects was conducted with Longissimus and fat gene expression data. Some powerful candidate genes and regions were identified such as the PBX1, RGS4, TRIB3 and a transcription regulatory element close to ELOVL6 gene to be further studied. Conclusions: Complementary genome scans have confirmed several chromosome regions previously associ

[EN] Background: Porcine fatty acid composition is a key factor for quality and nutritive value of pork. Several QTLs for fatty acid composition have been reported in diverse fat tissues. The results obtained so far seem to point out different genetic control of fatty acid composition conditional on the fat deposits. Those studies have been conducted using simple approaches and most of them focused on one single tissue. The first objective of the present study was to identify tissue-specific and tissue-consistent QTLs for fatty acid composition in backfat and intramuscular fat, combining linkage mapping and GWAS approaches and conducted under single and multitrait models. A second aim was to identify powerful candidate genes for these tissue-consistent QTLs, using microarray gene expression data and following a targeted genetical genomics approach. Results: The single model analyses, linkage and GWAS, revealed over 30 and 20 chromosomal regions, 24 of them identified here for the first time, specifically associated to the content of diverse fatty acids in BF and IMF, respectively. The analyses with multitrait models allowed identifying for the first time with a formal statistical approach seven different regions with pleiotropic effects on particular fatty acids in both fat deposits. The most relevant were found on SSC8 for C16:0 and C16:1(n-7) fatty acids, detected by both linkage and GWAS approaches. Other detected pleiotropic regions included one on SSC1 for C16:0, two on SSC4 for C16:0 and C18:2, one on SSC11 for C20:3 and the last one on SSC17 for C16:0. Finally, a targeted eQTL scan focused on regions showing tissue consistent effects was conducted with Longissimus and fat gene expression data. Some powerful candidate genes and regions were identified such as the PBX1, RGS4, TRIB3 and a transcription regulatory element close to ELOVL6 gene to be further studied. Conclusions: Complementary genome scans have confirmed several chromosome regions previously associ

The article proves that the genetic cluster analysis using of parents – offspring system at the period of 38 generations of directional intentional selection to short stem, the height of winter rye plants has been reduced less than 90 cm with simultaneously productivity integral components increasing. Directional selection on parent plants short stem has revealed pleiotropic effects to increasing averages of productivity yield capacity, spike length, flowers number, grains, and short stem and simultaneously its productivity reducing, plant and weight reducing of 100 direct descendants grains. Plant height donor of short stem Gnome 1 has been controlled prevailing by genetic factors and has been less influenced by environmental conditions. Selection by enlargement of elite plants grains has predetermined genetically increasing of the average height of families in the next generation without the concept selection requirements satisfaction. Therefore, the directed selections, by the structural analysis results, are annually held in two phases, first – to the expressed short stem and then among of them – to the high weight of 100 grains per plant and desirable productivity elements. A creative dominant short stem donor with stems up to 90 cm and a weight of 100 grains per plant more than 4.0 g has been made. A short stem spike shortness donor Dwarf 1possesses a significant reserve of common genetic mutation of quantitative characteristics, which can be used by direct and indirect selection. This population has been represented by its large amount, in order to enhance capabilities of directional selection plants short stem providing with the desired productivity components during the studying. Informative additive genetic cluster analysis is high. Plants productivity is considered to be extremely complicated selection characteristics, including many component constituents parts related genetically. One of these traits changing inevitably causes genetic changes in other b, Использованием генетического кластерного анализа в системе родители-потомки на протяжении 38 поколений направленной селекции по короткостебельности снижено высоту растений озимой ржи до 90 см при увеличении интегральных признаков определяющих продуктивность. Направленный отбор по короткостебельности родительских растений проявил плейотропный эффект на увеличение средних продуктивной кустистости, длины колоса, числа цветков в колосе, озерненности колоса при одновременном уменьшении продуктивности колоса, растения и массы 100 зерен прямых потомков. Высота растений донора Гном 1 контролировалась преимущественно генетическими факторами и мало зависела от влияния условий среды. Отбор по крупности зерна элитных растений обуславливал генетическое увеличение средней высоты семей в следующем поколении, что не удовлетворяло требованиям концепции селекции. Поэтому, направленные отборы по результатам структурного анализа ежегодно проводились в два этапа, сначала на выраженную короткостебельность, а среди них, на высокую массу 100 зерен с растения и желательными элементами продуктивности. Создан креативный донор доминантной короткостебельности с высотой стебля до 90 см и массой 100 зерен с растения 4,0 г. У донора короткостебельности имеется существенный резерв генетической изменчивости количественных признаков, который можно использовать прямым и косвенным отбором. За годы исследований популяция была представлена большим объемом для того, чтобы увеличить возможности проведения направленного отбора короткостебельных растений с желательными свойствами слагаемых продуктивности. Информативность генетического аддитивного кластерного анализа высокая. Продуктивность растения чрезвычайно сложный селекционный признак, который включает много компонентных слагаемых, генетически связанных между собой. Необходимо ставить перед собой цели, задачи, методически и генетически корректно использовать поток информации., Використанням генетичного кластерного аналізу в системі батьки-нащадки протягом 38 поколінь спрямованої селекції на короткостеблість зменшено висоту рослин жита озимого до 90 см з одночасним збільшенням інтегральних складових продуктивності. Спрямований добір за короткостеблістю батьківських рослин проявив плейотропний ефект на збільшення середніх величин продуктивної кущистості, довжини колоса, числа квіток, зерен, озерненості колоса та одночасного зменшення продуктивності колоса, рослини і маси 100 зерен прямих нащадків. Висота рослин донора короткостеблості Гном 1 контролювалася переважно генетичними чинниками й мало залежала від упливу умов середовища. Добір по крупності зернівки елітних рослин зумовлював генетичне збільшення середньої висоти сімей у наступному поколінні, що не задовольняло вимогам концепції селекції. Тому спрямовані добори за результатами структурного аналізу щорічно проводилися в два етапи. Перший – на виражену короткостеблість, а серед них – на високу масу 100 зерен з рослини та бажаними елементами продуктивності. Створено креативний донор домінантної короткостеблості з висотою стебла до 90 см і масою 100 зерен з рослини понад 4,0 г. У донора короткостеблості Гном 1 існує істотний резерв загальної генетичної мінливості кількісних ознак, який можна використовувати прямим і опосередкованим добором. За роки досліджень популяція представлена великим обсягом, з метою збільшення можливостей проведення спрямованого добору короткостеблових рослин з поєднанням бажаних складових продуктивності. Інформативність генетичного адитивного кластерного аналізу висока. Продуктивність рослини надзвичайно складна селекційна ознака, яка включає в себе багато складових компонентів, генетично пов’язаних між собою. Зміна однієї з цих ознак неодмінно зумовлює генетичну зміну інших селекційних ознак. Необхідно чітко ставити мету завдання, методично та генетично коректно використовувати потік інформації.

Background Porcine fatty acid composition is a key factor for quality and nutritive value of pork. Several QTLs for fatty acid composition have been reported in diverse fat tissues. The results obtained so far seem to point out different genetic control of fatty acid composition conditional on the fat deposits. Those studies have been conducted using simple approaches and most of them focused on one single tissue. The first objective of the present study was to identify tissue-specific and tissue-consistent QTLs for fatty acid composition in backfat and intramuscular fat, combining linkage mapping and GWAS approaches and conducted under single and multitrait models. A second aim was to identify powerful candidate genes for these tissue-consistent QTLs, using microarray gene expression data and following a targeted genetical genomics approach.Results The single model analyses, linkage and GWAS, revealed over 30 and 20 chromosomal regions, 24 of them identified here for the first time, specifically associated to the content of diverse fatty acids in BF and IMF, respectively. The analyses with multitrait models allowed identifying for the first time with a formal statistical approach seven different regions with pleiotropic effects on particular fatty acids in both fat deposits. The most relevant were found on SSC8 for C160 and C161(n-7) fatty acids, detected by both linkage and GWAS approaches. Other detected pleiotropic regions included one on SSC1 for C160, two on SSC4 for C160 and C182, one on SSC11 for C20:3 and the last one on SSC17 for C16:0. Finally, a targeted eQTL scan focused on regions showing tissue-consistent effects was conducted with Longissimus and fat gene expression data. Some powerful candidate genes and regions were identified such as the PBX1, RGS4, TRIB3 and a transcription regulatory element close to ELOVL6 gene to be further studied.Conclusions: Complementary genome scans have confirmed several chromosome regions previously associated to fatty

Background Porcine fatty acid composition is a key factor for quality and nutritive value of pork. Several QTLs for fatty acid composition have been reported in diverse fat tissues. The results obtained so far seem to point out different genetic control of fatty acid composition conditional on the fat deposits. Those studies have been conducted using simple approaches and most of them focused on one single tissue. The first objective of the present study was to identify tissue-specific and tissue-consistent QTLs for fatty acid composition in backfat and intramuscular fat, combining linkage mapping and GWAS approaches and conducted under single and multitrait models. A second aim was to identify powerful candidate genes for these tissue-consistent QTLs, using microarray gene expression data and following a targeted genetical genomics approach. Results The single model analyses, linkage and GWAS, revealed over 30 and 20 chromosomal regions, 24 of them identified here for the first time, specifically associated to the content of diverse fatty acids in BF and IMF, respectively. The analyses with multitrait models allowed identifying for the first time with a formal statistical approach seven different regions with pleiotropic effects on particular fatty acids in both fat deposits. The most relevant were found on SSC8 for C16:0 and C16:1(n-7) fatty acids, detected by both linkage and GWAS approaches. Other detected pleiotropic regions included one on SSC1 for C16:0, two on SSC4 for C16:0 and C18:2, one on SSC11 for C20:3 and the last one on SSC17 for C16:0. Finally, a targeted eQTL scan focused on regions showing tissue-consistent effects was conducted with Longissimus and fat gene expression data. Some powerful candidate genes and regions were identified such as the PBX1, RGS4, TRIB3 and a transcription regulatory element close to ELOVL6 gene to be further studied. Conclusions Complementary genome scans have confirmed several chromosome regions previously assoc

It is well established that Kisspeptin regulates the onset of puberty in vertebrates through stimulation of the secretion of gonadotropin-releasing hormones. However, the function of kisspeptin in peripheral tissues and in other functions is still poorly understood. Recently, the evolution and distribution of kisspeptin genes in vertebrates has been clarified. In contrast to placental mammals, which have a single gene for the ligand (Kiss) and for the receptor (Kissr), fish may have up to three Kiss genes and up to four Kissr genes because of genome duplications. However, information on the genomic structure of the piscine kiss and kissr genes is still scarce. Furthermore, when data from several species is taken together, interspecific differences in the expression of kiss and kissr during the reproductive cycle are found. Here, we discuss data gathered from several fish species, but mainly from two flatfishes, the Senegalese sole and the Atlantic halibut, to address general questions on kiss gene structure, regulation and function. Flatfish are among the most derived fish species and the two species referred to above have only one ligand and one receptor, probably because of the genome reduction observed in Pleuronectiformes. However, gene analysis shows that both species have an alternative splicing mechanism based on intron retention, but the functions of the alternative isoforms are unclear. In the Senegalese sole, sex-related differences in the temporal and spatial expression of kiss and kissr were observed during a whole reproductive cycle. In addition, recent studies suggested that kisspeptin system gene expression is correlated to energy balance and reproduction. This suggests that kisspeptin signaling may involve different sources of information to synchronize important biological functions in vertebrates, including reproduction. We propose a set of criteria to facilitate the comparison of kiss and kissr gene expression data across species

Fatty acid (FA) profiles of the Bt-maize line MON88017 expressing the Cry3Bb1 protein and its near-isogenic line DKC5143 were examined. Plant compartments under study included leaves taken from different internodes and roots. Sample preparation involved pressurized liquid extraction (PLE) of the biomass, transmethylation of the extracted lipids to give fatty acid methyl esters (FAMEs), and finally GC-MS analysis. The essential quality parameters for the FA profiles included total FA and sum of saturated FA, as well as double-bond index (DBI). FA profiles of the roots?characterized by high concentrations of homomorphic FA including palmitic and stearic acid, along with low concentrations of polyunsaturated surrogates?revealed high similarity between the genetically modified and the near-isogenic line. In contrast, FA profiles of the leaves showed significant differences: higher total FA concentrations and higher DBI were observed for the near-isogenic line. This was overwhelmingly associated with lower concentrations of a-linolenic acid (18:3?3,6,9ccc) in the genetically modified leaf samples. These differences were particularly pronounced for leaves taken from the fourth elongated, above-ground internode. Given the large reported variability in the population of maize lines, MON88017 and its near-isogenic line can be regarded as equivalent with regard to their fatty acid profiles, despite the differences observed for the leaves. Further experiments are needed to assess whether the genetic modification of Bt-maize plants might induce unintended effects with regard to FA profiles.

The development and progression of atherosclerosis comprises various processes, such as endothelial dysfunction, chronic inflammation, thrombus formation, and lipid profile modification. Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that have pleiotropic effects in addition to cholesterol-lowering properties. However, the mechanisms of these effects are not completely understood. Here, we investigated whether atorvastatin affects the levels of malondialdehyde-modified low-density lipoprotein (MDALDL), an oxidized LDL, the proinflammatory cytokine interleukin-6 (IL-6), or platelet P-selectin, a marker of platelet activation, relative to that of LDL cholesterol (LDL-C). Forty-eight patients with coronary artery disease and hyperlipidemia were separated into two groups that were administered with (atorvastatin group) or without (control group) atorvastatin. The baseline MDA-LDL level in all participants significantly correlated with LDL-C (r = 0.71, P < 0.01) and apolipoprotein B levels (r = 0.66, P < 0.01). Atorvastatin (10 mg/day) significantly reduced the LDL-C level within 4 weeks and persisted for a further 8 weeks of administration. Atorvastatin also reduced the MDA-LDL level within 4 weeks and further reduced it over the next 8 weeks. Platelet P-selectin expression did not change until 4 weeks of administration and then significantly decreased at 12 weeks, whereas the IL-6 level was gradually, but not significantly, reduced at 12 weeks. In contrast, none of these parameters significantly changed in the control group within these time frames. The reduction (%) in IL-6 between 4 and 12 weeks after atorvastatin administration significantly correlated with that of MDALDL and of platelet P-selectin (r = 0.65, P < 0.05 and r = 0.70, P < 0.05, respectively). These results suggested that the positive effects of atorvastatin on the LDL-C oxidation, platelet activation and inflammation that are involved in atherosclerotic processes are e, Heart and vessels, 23(4), pp.249-256; 2008