Windows of opportunity: Ocean warming shapes temperature-sensitive epigenetic reprogramming and gene expression across gametogenesis and embryogenesis in marine stickleback.

Rapid climate change is placing many marine species at risk of local extinction. Recent studies show that epigenetic mechanisms (e.g.

Histone Methylation Participates in Gene Expression Control during the Early Development of the Pacific Oyster .

Histone methylation patterns are important epigenetic regulators of mammalian development, notably through stem cell identity maintenance by chromatin remodeling and transcriptional control of pluripotency genes. But, the implications of histone marks are poorly understood in distant groups outside vertebrates and ecdysozoan models. However, the development of the Pacific oyster is under the strong epigenetic influence of DNA methylation, and histone-demethylase orthologues are highly expressed during .

Identification and expression of mangrove rivulus (Kryptolebias marmoratus) histone deacetylase (HDAC) and lysine acetyltransferase (KAT) genes.

During gametogenesis and embryonic development, precise regulation of gene expression, across cell/tissue types and over time, is crucial. In vertebrates, transcription is partly regulated by histone lysine acetylation/deacetylation, an epigenetic mechanism mediated by lysine acetyltransferases (KAT) and histone deacetylases (HDAC). Well characterized in mammals, these enzymes are unknown in fish embryology outside of zebrafish development.

The Kdm/Kmt gene families in the self-fertilizing mangrove rivulus fish, Kryptolebias marmoratus, suggest involvement of histone methylation machinery in development and reproduction.

Histone modifications such as methylation of key lysine residues play an important role in embryonic development in a variety of organisms such as of Pacific oysters, zebrafish and mice. The action of demethylase ("erasers") and methyltransferase ("writers") enzymes regulates precisely the methylation status of each lysine residue. However, despite fishes being very useful model organisms in medicine, evolution and ecotoxicology, most studies have focused on mammalian and plant model organisms, and mechanisms underlying regulation of histones are unknown in fish development outside of zebrafish.

DNA methylation in adults and during development of the self-fertilizing mangrove rivulus, .

In addition to genetic variation, epigenetic mechanisms such as DNA methylation might make important contributions to heritable phenotypic diversity in populations. However, it is often difficult to disentangle the contributions of genetic and epigenetic variation to phenotypic diversity. Here, we investigated global DNA methylation and mRNA expression of the methylation-associated enzymes during embryonic development and in adult tissues of one natural isogenic lineage of mangrove rivulus fish, .

Modulatory effect of the exudates released by the brown kelp Lessonia spicata on the toxicity of copper in early developmental stages of ecologically related organisms.

Lessonia spicata is a key dominant species along the Pacific coast of South America, providing a habitat for many organisms. However, this role can be affected by abiotic stress, such as metals. To counteract the toxic effect, L.

Delayed impacts of developmental exposure to 17-α-ethinylestradiol in the self-fertilizing fish Kryptolebias marmoratus.

17-α-ethinylestradiol (EE2) is one of the most potent endocrine disrupting compounds found in the aquatic environments, and is known to strongly alter fish reproduction and fitness. While the effects of direct exposure to EE2 are well studied in adults, there is an increasing need to assess the impacts of exposure during early life stages. Sensitivity to pollutants during this critical window can potentially affect the phenotype later in life or in subsequent generations.

Assessing uncertainty in sighting records: an example of the Barbary lion.

As species become rare and approach extinction, purported sightings can be controversial, especially when scarce management resources are at stake. We consider the probability that each individual sighting of a series is valid. Obtaining these probabilities requires a strict framework to ensure that they are as accurately representative as possible.

Temperature influences histone methylation and mRNA expression of the Jmj-C histone-demethylase orthologues during the early development of the oyster Crassostrea gigas.

In many groups, epigenetic mechanisms influence developmental gene regulation under environmental inputs. The Pacific oyster Crassostrea gigas belongs to lophotrochozoans and its larval development is highly dependent on temperature, but the role of epigenetic mechanisms in this context is unknown despite high levels of the recently characterized Jumonji histone demethylase (JHDM) orthologues (Cg_Jumonji) suggesting a physiological relevance of histone methylation in the oyster development. Because in other species alterations of the histone methylation pattern have deleterious outcomes, we investigated the influence of temperature during the oyster larval life on histone methylation and JHDM expression.

The Jumonji gene family in Crassostrea gigas suggests evolutionary conservation of Jmj-C histone demethylases orthologues in the oyster gametogenesis and development.

Jumonji (Jmj) proteins are histone demethylases, which control the identity of stem cells. Jmj genes were characterized from plants to mammals where they have been implicated in the epigenetic regulation of development. Despite the Pacific oyster Crassostrea gigas representing one of the most important aquaculture resources worldwide, the molecular mechanisms governing the embryogenesis and reproduction of this lophotrochozoan species remain poorly understood.

DNA methylation is crucial for the early development in the Oyster C. gigas.

In vertebrates, epigenetic modifications influence gene transcription, and an appropriate DNA methylation is critical in development. Indeed, a precise temporal and spatial pattern of early gene expression is mandatory for a normal embryogenesis. However, such a regulation and its underlying mechanisms remain poorly understood in more distant organisms such as Lophotrochozoa.

Examining the extinction of the Barbary lion and its implications for felid conservation.

Estimations of species extinction dates are rarely definitive, yet declarations of extinction or extirpation are important as they define when conservation efforts may cease. Erroneous declarations of extinctions not only destabilize conservation efforts but also corrode local community support. Mismatches in perceptions by the scientific and local communities risk undermining sensitive, but important partnerships.

A crucial role in fertility for the oyster angiotensin-converting enzyme orthologue CgACE.

Angiotensin-converting enzyme (ACE) is a highly conserved metallopeptidase. In mammals, the somatic isoform governs blood pressure whereas the germinal isoform (tACE) is required for fertility. In Ecdysozoans, ACE-like enzymes are implicated in reproduction.

Flavonoid-induced morphological modifications of endothelial cells through microtubule stabilization.

Flavonoids are common components of the human diet and appear to be of interest in cancer prevention or therapy, but their structure-activity relationships (SAR) remain poorly defined. In this study, were compared 24 flavonoids for their cytotoxicity on cancer cells (B16 and Lewis lung) and their morphological effect on endothelial cells (EC) that could predict antiangiogenic activity. Ten flavonoids presented inhibitory concentrations for 50% of cancer cells (IC50, 48 h) below 50 microM: rhamnetin, 3',4'-dihydroxyflavone, luteolin, 3-hydroxyflavone, acacetin, apigenin, quercetin, baicalein, fisetin, and galangin.

The immunophilin FKBP52 specifically binds to tubulin and prevents microtubule formation.

The FK506 binding protein FKBP52 belongs to the large family of immunophilins and is known as a steroid receptor-associated protein. Previous data suggest that FKBP52 is associated with the motor protein dynein and with the cytoskeleton during mitosis. Here we demonstrate a specific and direct interaction between FKBP52 and tubulin.

Microtubule-associated protein 2 (MAP2) is a neurosteroid receptor.

The neurosteroid pregnenolone (PREG) and its chemically synthesized analog 3beta-methoxypregnenolone (MePREG) bind to microtubule-associated protein 2 (MAP2) and stimulate the polymerization of microtubules. PREG, MePREG, and progesterone (PROG; the physiological immediate metabolite of PREG) significantly enhance neurite outgrowth of nerve growth factor-pretreated PC12 cells. However, PROG, although it binds to MAP2, does not increase the immunostaining of MAP2, contrary to PREG and MePREG.

MAPREG: toward a novel approach of neuroprotection and treatment of Alzheimer's disease.

MAPREG (microtubule-associated protein/neurosteroidal pregnenolone) is a start-up company that was created in October 2000. Its acronym recalls the basic discovery (Murakami et al., 2000) from which drug(s) will hopefully be developed that are useful for neuroprotection and repair in conditions such as post-traumatic and postischemic lesions, as well as defects proper to normal aging and neurodegenerative diseases, that is, principally Alzheimer's disease.

Microtubule-associated parameters as predictive markers of docetaxel activity in advanced breast cancer patients: results of a pilot study.

Docetaxel is currently one of the most active agents for breast cancer. Predictive markers of docetaxel efficacy are clearly needed in order to avoid unnecessary toxicity in nonresponding or resistant patients and to improve the cost-effectiveness ratio of docetaxel. This pilot study correlates the clinical efficacy of docetaxel in 54 metastatic or locally advanced breast cancer patients with the expression of microtubule-associated parameters evaluated by immunohistochemistry in archival tumor samples.

Occurrence of nuclear beta(II)-tubulin in cultured cells.

Microtubules are cylindrical organelles that play critical roles in cell division. Their subunit protein, tubulin, is a target for various antitumor drugs. Tubulin exists as various forms, known as isotypes.

SIAH-1 interacts with alpha-tubulin and degrades the kinesin Kid by the proteasome pathway during mitosis.

SIAH-1, a human homologue of the Drosophila seven in absentia (Sina), has been implicated in ubiquitin-mediated proteolysis of different target proteins through its N-terminal RING finger domain. SIAH-1 is also induced during p53-mediated apoptosis. Furthermore, SIAH-1-transfected breast cancer cell line MCF-7 exhibits an altered mitotic process resulting in multinucleated giant cells.

The genomic structure of c14orf1 is conserved across eukarya.

We have recently cloned the gene C14orf1, which is strongly expressed in normal testis and in several cancer cell lines and tumors. This gene maps to 14q24.3 and is interrupted by four introns.

Taxol resistance.

Background: Taxol has gained considerable attention in cancer therapy in recent years and is successfully used in treating a variety of tumors, including those of the breast, ovary and lung. Despite its preclinical and clinical success, the ability of tumors to develop an acquired resistance to drugs used for treatment remains a major obstacle to cancer cure. A better understanding of the various mechanisms of Taxol resistance may have important implications for strategies designed for cancer treatment.

Proteolysis of microtubule associated protein 2 and sensitivity of pancreatic tumours to docetaxel.

We have studied the state of microtubule associated protein 2 (MAP2) in the pancreatic ductal adenocarcinomas P03 and P02 (sensitive and refractory to docetaxel respectively) since they express the corresponding mRNA and MAP2-related peptides. Immunohistochemical localization showed that in tumour P03 the MAP2-related peptides are highly expressed and confined to the epithelial malignant cells while in P02 the Intensity of the immunostaining is lower. However, anti alpha-tubulin staining followed a similar pattern suggesting that the net amount of macromolecular structures in the sensitive tumour is higher than in the refractory one.

Pregnenolone binds to microtubule-associated protein 2 and stimulates microtubule assembly.

Fetal or adult rat-brain cytosol and fetal rat-brain microtubules contain a high-affinity, low-capacity pregnenolone-binding protein. The equilibrium dissociation constant is in the 30-50 nM range. The best competitors (in decreasing order) are pregnenolone sulfate, progesterone, Delta5-pregnene-3beta,20alpha-diol, and 3beta-hydroxy-5alpha-pregnan-20-one.