Global phylogeography of sailfish: deep evolutionary lineages with implications for fisheries management

Hydrobiologia - Since the Miocene profound climatic changes have influenced the biology and ecology of species worldwide, such as their connectivity, genetic population structure, and biogeography....     

Application Prospects for Synthetic Nanoparticles in Optogenetic Retinal Prosthetics

Journal of Evolutionary Biochemistry and Physiology - Optogenetic prosthetics is an approach to restore visual function in retinal degenerative diseases. It implies the delivery of genes encoding...     

Glutamate dehydrogenase requirement for apoptosis induced by aristolochic acid in renal tubular epithelial cells

Ingestion of aristolochic acids (AA) contained in herbal remedies results in a renal disease and, frequently, urothelial malignancy. The genotoxicity of AA in renal cells, including mutagenic DNA adduct formation, is well-documented. However, the mechanisms of AA-induced tubular atrophy and renal fibrosis are largely unknown. Epithelial cell death is a critical characteristic of these pathological conditions. To elucidate the mechanisms of AA-induced cytotoxicity, we explored AA-interacting proteins in tubular epithelial cells (TEC). We found that AA interacts with a mitochondrial enzyme glutamate dehydrogenase (GDH) and moderately inhibits its activity. We report that AA induces cell death in GDH-knockdown TEC preferentially via non-apoptotic means, whereas in GDH-positive cells, death was executed by both the non-apoptotic and apoptotic mechanisms. Apoptosis is an energy-reliant process and demands higher adenosine 5′-triphosphate (ATP) consumption than does the non-apoptotic cell death. We found that, after AAI treatment, the ATP depletion is more pronounced in GDH-knockdown cells. When we reduced ATP in TEC cells by inhibition of glycolysis and mitochondrial respiration, cell death mode switched from apoptosis and necrosis to necrosis only. In addition, in cells incubated at low glucose and no glutamine conditions, oxaloacetate and pyruvate reduced AAI-induced apoptosis our data suggest that AAI-GDH interactions in TEC are critical for the induction of apoptosis by direct inhibition of GDH activity. AA binding may also induce changes in GDH conformation and promote interactions with other molecules or impair signaling by GDH metabolic products, leading to apoptosis.     

NVP-LDE225, a Potent and Selective SMOOTHENED Antagonist Reduces Melanoma Growth In Vitro and In Vivo

Melanoma is one of the most aggressive cancers and its incidence is increasing worldwide. So far there are no curable therapies especially after metastasis. Due to frequent mutations in members of the mitogen-activated protein kinase (MAPK) signaling pathway, this pathway is constitutively active in melanoma. It has been shown that the SONIC HEDGEHOG (SHH)-GLI and MAPK signaling pathway regulate cell growth in many tumors including melanoma and interact with each other in the regulation of cell proliferation and survival.Here we show that the SHH-GLI pathway is active in human melanoma cell lines as they express downstream target of this pathway GLI1. Expression of GLI1 was significantly higher in human primary melanoma tissues harboring BRAF^V600E mutation than those with wild type BRAF. Pharmacologic inhibition of BRAF^V600E in human melanoma cell lines resulted in decreased expression of GLI1 thus demonstrating interaction of SHH-GLI and MAPK pathways. Inhibition of SHH-GLI pathway by the novel small molecule inhibitor of smoothened NVP-LDE225 was followed by inhibition of cell growth and induction of apoptosis in human melanoma cell lines, interestingly with both BRAF^V600E and BRAF^{Wild Type} status. NVP-LDE225 was potent in reducing cell proliferation and inducing tumor growth arrest in vitro and in vivo, respectively and these effects were superior to the natural compound cyclopamine.Finally, we conclude that inhibition of SHH-GLI signaling pathway in human melanoma by the specific smoothened inhibitor NVP-LDE225 could have potential therapeutic application in human melanoma even in the absence of BRAF^V600E mutation and warrants further investigations.     

Pericarp development and fruit structure in borassoid palms (Arecaceae-Coryphoideae-Borasseae)

Background and Aims

The Borasseae form a highly supported monophyletic clade in the Arecaceae–Coryphoideae. The fruits of Coryphoideae are small, drupaceous with specialized anatomical structure of the pericarp and berries. The large fruits of borassoid palms contain massive pyrenes, which develop from the middle zone of the mesocarp. The pericarp structure and mode of its development in Borasseae are similar to those of Eugeissona and Nypa. A developmental carpological study of borassoid palms will allow us to describe the process of pericarp development and reveal the diagnostic fruit features of borassoid palms, determine the morphogenetic fruit type in Borasseae genera, and describe similarities in fruit structure and pericarp development with other groups of palms.

Methods

The pericarp anatomy was studied during development with light microscopy based on the anatomical sections of fruits of all eight Borasseae genera.

Key Results

The following general features of pericarp structure in Borasseae were revealed: (1) differentiation of the pericarp starts at early developmental stages; (2) the exocarp is represented by a specialized epidermis; (3) the mesocarp is extremely multilayered and is differentiated into several topographical zones – a peripheral parenchymatous zone(s) with scattered sclerenchymatous elements and vascular bundles, a middle zone (the stony pyrene comprising networks of elongated sclereids and vascular bundles) and an inner parenchymatous zone(s); (4) differentiation and growth of the pyrene tissue starts at early developmental stages and ends long before maturation of the seed; (5) the inner parenchymatous zone(s) of the mesocarp is dramatically compressed by the mature seed; (6) the endocarp (unspecialized epidermis) is not involved in pyrene formation; and (7) the spermoderm is multilayered in Hyphaeninae and obliterated in Lataniinae.

Conclusions

The fruits of Borasseae are pyrenaria of Latania-type. This type of pericarp differentiation is also found only in Eugeissona and Nypa. The fruits of other Coryphoideae dramatically differ from Borasseae by the pericarp anatomical structure and the mode of its development.     

Identification of TRPM5 Ion Channels in Type-II Taste Cells of Mice

TRPM5 are ion channels belonging to the TRP family, which demonstrate a nonselective permeability for monovalent cations and are activated by an increase in the intracellular calcium level. TRPM5 are present in taste receptor cells of type II responsible for reception of bitter, sweet, and umami taste sensations. Knockout of the trpm5 gene in mice results in a nearly complete loss of sensitivity to taste stimuli of the above-mentioned modalities (taste blindness). The physiological activity of TRPM5 in taste receptive cells has practically not been studied. Using a patch-clamp technique, we carried out a comparative analysis of the properties of recombinant TRPM5 and Ca²⁺-activated membrane channels in type-II taste cells in mice. Dialysis of the studied cells with a high-Ca²⁺ solution and application of a calcium ionophore, ionomycin, caused activation of outward-rectification ion channels permeable for Na⁺, Cs⁺, and K⁺ in CHO-strain cells with exogenous TRPM5. These channels were blocked by 100 μM triphenylphosphine oxide (TPPO). Calcium-activated channels in type-II taste cells also possessed analogous properties. Application of the calcium ionophore ionomycin or a stepwise increase in the intracellular Ca²⁺ level using photolysis (uncaging) caused activation of channels nonselective with respect to Na⁺ and Cs⁺ and impermeable for N-methyl-D-glucamine (NMDG⁺). These channels had the current–voltage characteristics of outward rectification and a high thermosensitivity (Q₁₀ = 6.7 ± 0.5); they could be blocked by TPPO. It should be emphasized that TRPM5 were specific with respect to type-II cells. An increase in the intracellular calcium level induced the appearance of Cl– current in type-I cells and did not influence the basic current in type-III cells.     

On Homology between the Neural Complex of Tunicates and the Hypophysis of Vertebrates

The organs of the tunicate neural complex and parts of the vertebrate hypophysis were compared on the basis of morphological, physiological, embryological, and endocrinological debatable data. The hypothesis of the homology between the tunicate neural gland and ciliary organ (together with the dorsal tube) and the vertebrate neurohypophysis and adenohypophysis, respectively, is substantiated. In contrast to the hypophysis, the neural complex is a multifunctional structure. The presence of hormonelike substances (typical of the adenohypophysis) in the neural gland testifies to the independent evolution of the neural complex and hypophysis, both of them originating from some “protohypophysis” of hypothetical protovertebrates.