Immunocytochemical techniques, electrophysiology and calcium imaging in mouse hippocampal slices revealed that hippocampal astrocytes express functional cannabinoid receptors type 1 (CB1). These receptors can be activated both by synthetic agonists such as endocannabinoids from pyramidal neurons. Their activation leads to sequential stimulation of Gq/11 protein and phospholipase C which causes the release of calcium from intracellular reservoirs, which generate increases in intracellular calcium. Increased calcium serves as a signal that triggers the release of transmitter glutamate.

Glutamate released by astrocytes activated receptors in the membrane of adjacent neurons, causing slow input currents that increase neuronal excitability. That is, the stimulation of astrocytes by endocannabinoids activate a new channel of communication between neurons, where astrocytes serve as a bridge in this communication.

The results show that astrocytes are cellular targets of cannabinoids, and identify them as new cellular elements involved in the physiology of addiction and possible targets for the treatment of cannabinoids as drugs of abuse. Further, considering the importance of endocannabinoids in many processes of the nervous system, such as pain perception or learning and memory, these findings indicate that astrocytes are actively involved in brain function.

In this process the enzyme glutamine synthetase (GS) plays a key role, since most of the channels towards the production of ammonium nitrogen compounds: proteins, nucleic acids, chlorophylls, polyamines and a variety of secondary metabolism molecules. In a Ávila Concepción study led by and conducted in the Department of Molecular Biology and Biochemistry, University of Malaga has managed to characterize a transcription factor family DOF in conifers (Pinus pinaster Ait) that regulates the expression of two genes of GS (GS1a and GS1B) differentially.

While operating as GS1B activator whose expression is localized mainly in vascular tissue also acts as a repressor of GS1a whose expression is localized preferentially on photosynthetic cells. Thus, a single transcription factor would be responsible for the spatial distribution of two isoforms of GS that play differential and nonredundant roles in the process of assimilation of ammonium in the plant.

This work has succeeded in proposing a useful regulatory model for the expression of GS, which allows to know how it regulates nitrogen assimilation in woody plants. This achievement represents a major step in understanding the function of genes that control key aspects of plant development, which are involved in the expression of economic important traits related to productivity and agroforestry.

Since the early eighties, it was shown that the onset of division cycle required the products of genes cdc2 and Cdc10. Of these, Cdc10 is part of a transcription factor known as CSM and whose activity is required for transcription of genes necessary to complete the S phase of cell cycle. At this time, and by proteomic approaches, experts are trying to figure out how this transcription factor regulates parallel cell cycle progression. In the context of this cycle, also want to know the mechanism for maintaining the quiescent phase in most cells of the body. Some MAP kinases seem to be decisive in the survival in stationary phase and, therefore, very important for chronological aging.

Finally, meiosis is the only exception to the normal cell cycle, as it has two nuclear divisions (phases of meiosis I and II), without interference by DNA synthesis. The cells of S. pombe require the activity of a meiosis-specific cyclin, REM1, for progress in the course of meiosis. Various research groups working today trying to characterize the role during these stages of meiosis and its transcriptional regulation. 3

The gene encoding REM1 contains an intron with a stop codon in the reading frame, so to be processed (via splicing) to ensure it fully mature protein. REM1 messenger RNA is expressed throughout meiosis but its intron is processed only at the stage of meiosis I.
The group at the Universitat Pompeu Fabra, led by Jose Ayte recently described in Nature, that the messenger RNA processing REM1 encodes a truncated protein of 17 kDa required for recombination levels are normal, whereas in meiosis I — intron-processed after the protein is expressed in mature, 56 kDa, with basic functions necessary for proper progression of meiosis.

In this study we have determined, on a molecular scale, two transcription factors Forkhead family / Winged-helix regulate this process by binding both to the promoter of REM1. Fkh2, prevents the processing of messenger RNA REM1 during the premeiotic DNA synthesis, while promoting Mei4 intron processing in meiosis I. The process is carried out by a physical interaction with Mei4 running the splicing machinery (spliceosomes).

Jose Ayte graduated in Pharmacy from the University of Barcelona and in 1990 defended his doctoral thesis under the direction of Fausto García Hegardt, Faculty of Pharmacy, University of Barcelona. He has made several postdoctoral abroad, highlighting their involvement in the project five years in research on cell cycle control in the laboratory of James A. DeCaprio, Dana-Farber Cancer Institute and Harvard Medical School. He has also done research with Paul Nurse at the Imperial Cancer Research Fund in London.

This study conducted by Joseph J. Luke Center for Molecular Biology ‘Severo Ochoa’ is proposed to determine whether calcium permeability contributes to synaptic alterations and neuronal apoptosis described in HD. An increase in P2X7 receptor expression in animal models, plus an altered permeability to calcium-mediated P2X7 both presynaptically, as in neuronal cell bodies. The neurons expressing mutant huntingtin were more susceptible to apoptosis by P2X7 receptor activation. Finally, in vivo administration of HD transgenic mice BBG antagonist prevented the neuronal apoptosis and attenuated body weight loss and motor coordination deficits of more advanced stages of work animal.Este model posits the P2X7 receptor as a therapeutic target in HD and other neurodegenerative diseases.

The trimethylation of histone H3 at residue lysine 4 (H3K4me3) is a crucial signal activation of gene expression. ORC1 protein is the subunit complex recognition of the origins of DNA replication. Besides, in yeast and humans, ORC1 functions as a transcriptional repressor of certain genes such as c-Myc in humans.Work by Maria de la Paz Sanchez and Crisanto Gutierrez of the Center for Molecular Biology ‘Severo Ochoa’, ORC1 has established that also functions as a transcriptional activator of certain genes in the plant Arabidopsis thaliana, a surprising result given the conservation of amino acids and structural domains between yeast, human and plants.

The structural basis of the role of ORC1 is the presence of a PHD domain at the N-terminal is able to interact specifically with residues H3K4me3 promoters of target genes. This binding is associated with increased acetylation of histone H4 and trimethylation of residue K20 of histone H4 (H4K20me3). The paper concludes that, unlike what happens in humans, H4K20me3 is associated with activation and not repression transcipcional. These data provide a molecular basis to explain ORC1 opposing functions in transcriptional regulation. The work also reveals that ORC1 would be a new class of effectors that bind H3K4me3 and activate transcription in all vegetable organisms.

The experiments show that the modified protein is unable to interact with ET-1 mRNA, resulting in a decoupling of its degradation, favoring its accumulation. With the mechanism described, the cells can respond dynamically to free radical damage through changes in the expression of certain genes, such as ET-1. This response is via the enzyme GAPDH, a protein originally thought unique metabolic function in glycolysis and, latterly, have been attributed other functions in processes such as cell death or DNA repair.

The results show clear differences in response to Ca 2 + between the brain affected and controls specific to the activity of the plasma membrane ATPase (PMCA) and observed in AD brain stimulation at low concentrations of Ca 2 + and less inhibition at high concentrations.Control membranes show a similar dependence on Ca 2 + only after the addition of β-amyloid peptide.

The results indicate that altered sensitivity to Ca 2 + ATPase activity in AD is due to the presence of B-amyloid in the affected tissue. The effects are specific and not present in all isoforms. Moreover, the action of β-amyloid is zero to high concentrations of cholesterol, which could modify the conformation of the PMCA or facilitate peptide binding to the membrane, affecting the interaction péptidoproteína.

In short, this study reveals that the neurotoxic process in AD is partly mediated by an interaction between β-amyloid and the PMCA, which affects their ability to regulate Ca 2 +, and opens prospects for addressing new therapeutic strategies.