On the possible existence of a liver LDL-ostat, and its malfunctioning in familial hypercholesterolemia.

The investigation of familial hypercholesterolemia (FH) and its relationship to atherosclerosis has led to enormous scientific and medical progress, including the identification of genetic defects underlying FH, the elucidation of molecular mechanisms crucial for cellular cholesterol homeostasis and the development of current pharmaceutical tools for FH treatment (which are directed at increasing LDL uptake). These successes also led to the establishment of a model centered on cellular rather than whole organism processes, and a view of FH as resulting from a deficiency in LDL uptake. On the other hand, whole organism fluxes of cholesterol (like those of other nutrients) are centered on the liver, LDL (ultimately derived from the liver) is the main cholesterol transporter in plasma, and there is evidence of evolutionary pressure favoring mechanisms to maintain LDL plasma concentrations.

Patterns and tempo of PCSK9 pseudogenizations suggest an ancient divergence in mammalian cholesterol homeostasis mechanisms.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a central role in cholesterol homeostasis in humans as a major regulator of LDLR levels. PCSK9 is an intriguing protease in that it does not act by proteolysis but by preventing LDLR recirculation from endosomes to the plasma membrane. This, and the inexistence of any other proteolytic substrate but itself could suggest that PCSK9 is an exquisite example of evolutionary fine-tuning.

New Mitochondrial Gene Rearrangement in , and (Hymenoptera: Braconidae), Three Parasitoid Species of Economic Interest.

The family Braconidae consists mostly of specialized parasitoids, some of which hold potential in biocontrol of agricultural pests. and are parasitoids associated with , a major pest of cultivated olives. The native range of is the Mediterranean, and and are native to sub-Saharan Africa.

Strategies to prevent cleavage of the linker region between ligand-binding repeats 4 and 5 of the LDL receptor.

A main strategy for lowering plasma low-density lipoprotein (LDL) cholesterol levels is to increase the number of cell-surface LDL receptors (LDLRs). This can be achieved by increasing the synthesis or preventing the degradation of the LDLR. One mechanism by which an LDLR becomes non-functional is enzymatic cleavage within the 10 residue linker region between ligand-binding repeats 4 and 5.

The complete mitochondrial genome of Bactrocera biguttula (Bezzi) (Diptera: Tephritidae) and phylogenetic relationships with other Dacini.

Bactrocera biguttula is an African olive fruit fly that does not attack cultivated olives but rather develops in the fruits of wild species of Olea and Noronhia. The complete mitochondrial genome of an individual specimen was characterized in comparison to other Bactrocera. The phylogenetic relationships of B.

Evolution of the NET (NocA, Nlz, Elbow, TLP-1) protein family in metazoans: insights from expression data and phylogenetic analysis.

The NET (for NocA, Nlz, Elbow, TLP-1) protein family is a group of conserved zinc finger proteins linked to embryonic development and recently associated with breast cancer. The members of this family act as transcriptional repressors interacting with both class I histone deacetylases and Groucho/TLE co-repressors. In Drosophila, the NET family members Elbow and NocA are vital for the development of tracheae, eyes, wings and legs, whereas in vertebrates ZNF703 and ZNF503 are important for the development of the nervous system, eyes and limbs.

Extensive regulation of nicotinate phosphoribosyltransferase (NAPRT) expression in human tissues and tumors.

Nicotinamide adenine dinucleotide (NAD) is a cofactor in redox reactions and a substrate for NAD-consuming enzymes, such as PARPs and sirtuins. As cancer cells have increased NAD requirements, the main NAD salvage enzymes in humans, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase (NAPRT), are involved in the development of novel anti-cancer therapies. Knowledge of the expression patterns of both genes in tissues and tumors is critical for the use of nicotinic acid (NA) as cytoprotective in therapies using NAMPT inhibitors.

Marked Genetic Differentiation between Western Iberian and Italic Populations of the Olive Fly: Southern France as an Intermediate Area.

The olive fly, Bactrocera oleae, is the most important pest affecting the olive industry, to which it is estimated to cause average annual losses in excess of one billion dollars. As with other insects with a wide distribution, it is generally accepted that the understanding of B. oleae population structure and dynamics is fundamental for the design and implementation of effective monitoring and control strategies.

The mitochondrial genome of Prays oleae (Insecta: Lepidoptera: Praydidae).

Prays oleae is one of the most important olive tree pests and a species of interest in evolutionary studies, as it belongs to one of the oldest extant superfamilies of Ditrysian Lepidoptera. We determined its mitogenome sequence, and found it has common features for Lepidoptera, e.g.

The complete mitochondrial genome of Parage aegeria (Insecta: Lepidoptera: Papilionidae).

Pararge aegeria is a palearctic butterfly used as a model organism in ecology, behavior, evolution and development, with significant geographically-correlated morphological variation and two close relatives in Macaronesia. In this study, I have determined the complete mitogenome sequence of P. aegeria.

GRG5/AES interacts with T-cell factor 4 (TCF4) and downregulates Wnt signaling in human cells and zebrafish embryos.

Transcriptional control by TCF/LEF proteins is crucial in key developmental processes such as embryo polarity, tissue architecture and cell fate determination. TCFs associate with β-catenin to activate transcription in the presence of Wnt signaling, but in its absence act as repressors together with Groucho-family proteins (GRGs). TCF4 is critical in vertebrate intestinal epithelium, where TCF4-β-catenin complexes are necessary for the maintenance of a proliferative compartment, and their abnormal formation initiates tumorigenesis.

Characterization of human NLZ1/ZNF703 identifies conserved domains essential for proper subcellular localization and transcriptional repression.

NET family members have recently emerged as important players in the development of multiple structures, from the trachea of fly larvae to the vertebrate eye and human breast cancers. However, their mechanisms of action are still poorly understood, and we lack a detailed characterization of their functional domains, as well as gene expression patterns-particularly in adult mammals. Here, we present a characterization of human NLZ1/ZNF703 (NocA-like zinc finger 1/Zinc finger 703), one of the two human NET family member genes.

Mitochondrial haplotypes reveal olive fly (Bactrocera oleae) population substructure in the Mediterranean.

The olive fly (Bactrocera oleae) is the most important olive tree (Olea europaea) pest. In the Mediterranean basin, where 98 % of its main hosts are concentrated, it causes major agricultural losses, due to its negative effect on production and quality of both olive and olive oil. Previous phylogeographic analyses have established that Mediterranean olive fly populations are distinct from other Old World populations, but did not agree on the specific population substructure within this region.

Transcriptional regulation of the human mitochondrial peptide deformylase (PDF).

The last years of research have been particularly dynamic in establishing the importance of peptide deformylase (PDF), a protein of the N-terminal methionine excision (NME) pathway that removes formyl-methionine from mitochondrial-encoded proteins. The genomic sequence of the human PDF gene is shared with the COG8 gene, which encodes a component of the oligomeric golgi complex, a very unusual case in Eukaryotic genomes. Since PDF is crucial in maintaining mitochondrial function and given the atypical short distance between the end of COG8 coding sequence and the PDF initiation codon, we investigated whether the regulation of the human PDF is affected by the COG8 overlapping partner.

CDX2 autoregulation in human intestinal metaplasia of the stomach: impact on the stability of the phenotype.

Background And Aims: Intestinal metaplasia (IM) is a gastric preneoplastic lesion that appears following Helicobacter pylori infection and confers an increased risk for development of cancer. It is induced by gastric expression of the intestine-specific transcription factor CDX2. The regulatory mechanisms involved in triggering and maintaining gastric CDX2 expression have not been fully elucidated.

Genetic alterations in lung cancer: assessing limitations in routine clinical use.

Lung cancer is the most frequent cause of cancer mortality worldwide, responsible for approximately 1.1 million deaths per year. Median survival is short, both as most tumours are diagnosed at an advanced stage and because of the limited efficacy of available treatments.

Exploring and exploiting instability.

Genetic instability was postulated to be essential for tumor development almost three decades ago, and yet its exact nature in and relationship with cancer continue to be ill-understood and hotly debated subjects. In this article, we review and discuss current knowledge and thinking about the existence, characteristics, reasons for and mechanisms of genetic instability in human cancers, as well as how its study can help us better understand and fight cancer. Particular emphasis is given to chromosomal instability, the most common and least understood of the types of genetic instability found in human tumors.