Physiological effects of KDM5C on neural crest migration and eye formation during vertebrate development

Background: Lysine-specific histone demethylase 5C (KDM5C) belongs to the jumonji family of demethylases and is specific for the di- and tri-demethylation of lysine 4 residues on histone 3 (H3K4 me2/3). KDM5C is expressed in the brain and skeletal muscles of humans and is associated with various biologically significant processes. KDM5C is known to be associated with X-linked mental retardation and is also involved in the development of cancer. However, the developmental significance of KDM5C has not been explored yet. In the present study, we investigated the physiological roles of KDM5C during Xenopus laevis embryonic development. Results: Loss-of-function analysis using kdm5c antisense morpholino oligonucleotides indicated that kdm5c knockdown led to small-sized heads, reduced cartilage size, and malformed eyes (i.e., small-sized and deformed eyes). Molecular analyses of KDM5C functional roles using whole-mount in situ hybridization, -galactosidase staining, and reverse transcription-polymerase chain reaction revealed that loss of kdm5c resulted in reduced expression levels of neural crest specifiers and genes involved in eye development. Furthermore, transcriptome analysis indicated the significance of KDM5C in morphogenesis and organogenesis. Conclusion: Our findings indicated that KDM5C is associated with embryonic development and provided additional information regarding the complex and dynamic gene network that regulates neural crest formation and eye development. This study emphasizes the functional significance of KDM5C in Xenopus embryogenesis; however, further analysis is needed to explore the interactions of KDM5C with specific developmental genes

Beneficial effects of n-3 PUFA on chronic airway inflammatory diseases.

Chronic airway inflammation is a common symptom of several diseases such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. Excessive or inappropriate immune system activity and/or failure to resolve an acute inflammation spontaneously can induce functional changes in the walls and parenchyma of the airways. Continuous recruitment of inflammatory cells to the site of inflammation and the production of protein (i.e., cytokines, chemokines, enzymes, etc.) and lipid (eicosanoids) pro-inflammatory mediators contribute directly or indirectly to changes in airway structure and function. Pro-inflammatory eicosanoids are mainly formed by the metabolism of arachidonic acid, an n-6 polyunsaturated fatty acid esterified at the s-n2 position of membrane phospholipids. Unlike n-6 polyunsaturated fatty acids (PUFA), n-3 PUFA decrease inflammation. The anti-inflammatory effect of n-3 PUFA derives from their ability to compete with arachidonic acid in the production of eicosanoids, thereby decreasing the production of pro-inflammatory cytokines and reducing immune cell functions. Moreover, n-3 PUFA can give rise to a series of pro-resolving mediators with anti-inflammatory actions, such as resolvins and protectins. While most studies have reported n-3 PUFA to have beneficial effects on chronic airway diseases, some have questioned the anti-inflammatory effects of n-3 PUFA in inflammatory airway diseases. This paper summarizes the main mechanisms by which n-3 PUFA exert anti-inflammatory and pro-resolving effects, focusing on their use in airway disorders with an inflammatory component

Observations sur I\u27écologie et la distribution des Turbellariés Tricladides dépigmentés et anophtalmes de Roumanie

Twenty-two localities, where unpigmented and mostly blind tricladid turbellarians (Dendrocoelidae and Fonticola) were discovered by the author, are described in more or less detail. These animals are particularly well represented in Romania; the explanation is that they are expansive offshoots of a fauna formerly inhabiting the huge brackish or freshwater lakes which covered most of this country during the Neogene (and especially the Sarmatian). Different species are inhabitants of different particular habitats of the underground water realm, and the author distinguishes between species inhabiting cave waters, typical phreatobionts, hyporheic species and species living in springs or springbrooks. These species are sensitive indicators of even small changes affecting the abiotic or biotic conditions prevailing in their habitats (several examples are offered, especially of competitive exclusion)

Lipids in the nutritional treatment of inflammatory diseases | Ruolo dei lipidi nel trattamento nutrizionale delle patologie infiammatorie

Fatty acids can be broadly divided into saturated, monounsaturated and polyunsaturated acids on the basis of the number of double bonds. Depending on the position of the first double bond, counted from the methyl end, polyunsaturated fatty acids can be further subdivided into series n-3 or n-6. Dietary fatty acids, mainly consisting of essential fatty acids linoleic acid (C18:2, n-6) and linolenic acid (C18:3, n-3), in mammalian cells can be further elongated or desaturated (with the addition of more double bonds). As the elongation and desaturation enzymes are the same for both n-6 and n-3 fatty acids, the two series compete for the same pattern of enzymes for their transformation into fatty acids with a higher number of carbon atoms and double bonds. Polyunsaturated fatty acids of the n-6 and n-3 series are used in the cells mainly as components of biological membrane phospholipids. Following an injurious stimulus starting an inflammatory process, polyunsaturated fatty acids of membrane phospholipids are released into the cell and are transformed into molecules called eicosanoids. Eicosanoids derived from fatty acids of the n-6 series have generally a proinflammation effect, while eicosanoids derived from fatty acids of the n-3 series have an anti-inflammatory and resolutive effect on the triggered inflammatory process. Taken together, these considerations suggest that the introduction of polyunsaturated fatty acids of the n-3 series in an appropriate ratio with respect to fatty acids of the n-6 series may reduce both acute and chronic effects of inflammation. Beneficial effects from the use of polyunsaturated fatty acids of the n-3 series have also been reported in allergic diseases and some forms of respiratory diseases

Low level of hydrogen peroxide induces lipid synthesis in BRL-3A cells through a CAP-independent SREBP-1a activation.

Although H2O2 is traditionally known to have cytotoxic effects, recent studies argue about its regulatory role on lipid metabolism. However, the mechanism underlying the induction of lipid biosynthesis by oxidative stress still remains unknown. To shed light on this aspect we investigated the H2O2-induced lipogenesis in rat liver BRL-3A cells. We found that a short-term exposition of cells to 35 μM H2O2 didn’t cause any significant sign of cell damage measured by following diene formation and lactate dehydrogenase release from cells. However, in this stressful condition, a significant increase of [1-14C]acetate incorporation into fatty acids and cholesterol, associated to an increase in the activity and expression of key enzymes of fatty acid and cholesterol synthesis, were measured. mRNA and protein contents of the transcription factors SREBP-1 and SREBP-2, involved in the activation of lipid synthesis, increased as well. The analysis of molecular mechanism of SREBP-1 activation revealed, in treated compared to control cells, a higher SREBP-1a mRNA translation involving an internal ribosome entry side (IRES), present in the leader region of its mRNA. Longer exposition to the pro-oxidant induced a progressive loss of cell viability together with an increase of cell triacylglycerol content