quarta-feira, 1 de outubro de 2014

Functional diversity in the color vision of cichlid fishes

Functional diversity in the color vision of cichlid fishes
Diversidade Funcional na visão em cores dos peixes ciclídeos.

Authors: Shai Sabbah, Raico Lamela Laria, Suzanne M Gray & Craig W Hawryshyn

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Abstract
Background: Color vision plays a critical role in visual behavior. An animal’s capacity for color vision rests on the presence of differentially sensitive cone photoreceptors. Spectral sensitivity is a measure of the visual
responsiveness of these cones at different light wavelengths. Four classes of cone pigments have been identified in vertebrates, but in teleost fishes, opsin genes have undergone gene duplication events and thus can produce a larger number of spectrally distinct cone pigments. In this study, we examine the question of large-scale variation in color vision with respect to individual, sex and species that may result from differential expression of cone pigments. Cichlid fishes are an excellent model system for examining variation in spectral sensitivity because they have seven distinct cone opsin genes that are differentially expressed.
Results: To examine the variation in the number of cones that participate in cichlid spectral sensitivity, we used whole organism electrophysiology, opsin gene expression and empirical modeling. Examination of over 100 spectral sensitivity curves from 34 individuals of three species revealed that (1) spectral sensitivity of individual cichlids was based on different subsets of four or five cone pigments, (2) spectral sensitivity was shaped by multiple cone interactions and (3) spectral sensitivity differed between species and correlated with foraging mode and the spectral reflectance of conspecifics. Our data also suggest that there may be significant differences in opsin gene expression between the sexes.
Conclusions: Our study describes complex opponent and nonopponent cone interactions that represent the
requisite neural processing for color vision. We present the first comprehensive evidence for pentachromatic color vision in vertebrates, which offers the potential for extraordinary spectral discrimination capabilities. We show that opsin gene expression in cichlids, and possibly also spectral sensitivity, may be sex-dependent. We argue that females and males sample their visual environment differently, providing a neural basis for sexually dimorphic visual behaviour. The diversification of spectral sensitivity likely contributes to sensory adaptations that enhance the contrast of transparent prey and the detection of optical signals from conspecifics, suggesting a role for both natural and sexual selection in tuning color vision.



Juno is the egg Izumo receptor and is essential for mammalian fertilization / Juno é o receptor Izumo do ovo e é essencial para a fertilização de mamíferos

Juno is the egg Izumo receptor and is essential for mammalian fertilization
Juno é o receptor Izumo do ovo e é essencial para a fertilização de mamíferos

Authors: Enrica Bianchi, Brendan Doe, David Goulding & Gavin J. Wright

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Fertilization occurs when sperm and egg recognize each other and fuse to form a new, genetically distinct organism. The molecular basis of sperm–egg recognition is unknown, but is likely to require interactions between receptor proteins displayed on their surface. Izumo1 is an essential sperm cell-surface protein, but its receptor on the egg has not been described. Here we identify folate receptor 4 (Folr4) as the receptor for Izumo1 on the mouse egg, and propose to rename it Juno. We show that the Izumo1–Juno interaction is conserved within several mammalian species, including humans. Female mice lacking Juno are infertile and Juno-deficient eggs do not fuse with normal sperm. Rapid shedding of Juno fromthe oolemmaafter fertilization suggests amechanismfor themembrane block to polyspermy, ensuring eggs normally fuse with just a single sperm. Our discovery of an essential receptor pair at the nexus of conception provides opportunities
for the rational development of new fertility treatments and contraceptives.


quinta-feira, 25 de setembro de 2014

Heat shock protein 90 inhibitors in non-small-cell lung cancer // Inibidores da proteína de choque térmico 90 em câncer de pulmão de células não-pequenas.

Heat shock protein 90 inhibitors in non-small-cell lung cancer


Inibidores da proteína de choque térmico 90 em câncer de pulmão de células não-pequenas.


Author: Rathi N. Pillai and Suresh S. Ramalingam
Autor:Rathi N. Pillai & Suresh S. Ramalingam

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 Versão traduzida para o Português, clique aqui.


Purpose of review
Heat shock protein 90 (Hsp90) protects cellular proteins from degradation by the ubiquitin-proteasome system in conditions of stress. Many cancers have increased expression of Hsp90 to ensure their malignant phenotype of increased proliferation, decreased apoptosis, and metastatic potential by conservation of proteins like epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2, anaplastic lymphoma kinase (ALK), v-Raf murine sarcoma viral oncogene homologue B1, AKT, B-cell lymphoma 2, and cell cycle proteins. This review discusses recent developments in the strategy of Hsp90 inhibition as a targeted therapy in non-small-cell lung cancer (NSCLC).
Recent findings
Hsp90 inhibitors result in growth inhibition and tumor regression in NSCLC cell lines and tumor xenograft models, both as monotherapy and in combination with other drugs. Hsp90 inhibition has particular efficacy in molecular subtypes of NSCLC, such as EGFR-mutated and ALK-rearranged NSCLC. IPI-504 and ganetespib have activity in NSCLC both as monotherapy and in combination with docetaxel.
Summary
Preclinical studies and early clinical trials have confirmed the efficacy of Hsp90 inhibition as a targeted therapy in NSCLC. Ongoing trials will further define the utility of Hsp90 inhibitors in NSCLC.

Keywords
anaplastic lymphoma kinase, epidermal growth factor receptor, ganetespib, heat shock protein 90 inhibitors, non-small-cell lung cancer.




Objetivo da revisão
A proteína de choque térmico 90 (Hsp90) protege as proteínas celulares da degradação pelo sistema ubiquitina-proteassoma em condições de estresse. Muitos cânceres têm aumentado a expressão da Hsp90 para garantir seu fenótipo maligno com o aumento da proliferação, diminuição da apoptose e a potencial metástase pela conservação das proteínas como receptor do fator de crescimento epidérmico (EGFR), receptor 2 do fator de crescimento epidérmico humano, linfoma anaplásico quinase (ALK), homólogo B1 do oncogene viral de sarcoma murino v-Raf, AKT, linfoma 2 da célula B e proteínas do ciclo celular. Esta revisão discute os recentes desenvolvimentos na estratégia da inibição da Hsp90 como uma terapia alvo em câncer de pulmão de células não-pequenas (NSCLC).
Descobertas Recentes
Os inibidores da Hsp90 resultam em crescimento da inibição e regressão de tumor em linhagens de células em NSCLC e modelos xenotransplante de tumor, ambos como uma monoterapia e em combinação com outras drogas. A inibição da Hsp90 tem uma eficácia particular em subtipos de moléculas de NSCLC, como por exemplo EGFR mutante e ALK rearranjado. IPI-504 (inibidor da Hsp90) e “Ganetespib” (um remédio inibidor da Hsp90) têm atividade em NSCLC ambos como uma monoterapia e em combinação com docetaxel (um remédio contra o câncer).
Resumo
Estudos pré-clínicos e estudos clínicos recentes têm confirmado a eficácia da inibição da Hsp90 como um alvo da terapia em NSCLC. Os estudos em andamento vão definir ainda mais a utilidade dos inibidores da Hsp90 em NSCLC.
Palavras-chave
Linfoma anaplásico quinase, receptor do fator de crescimento epidérmico, “Ganetespib”, inibidores da proteína de choque térmico 90, câncer de pulmão em células não-pequenas.

quinta-feira, 17 de abril de 2014

Modulation of rhythmic brain activity by diazepam:GABAA receptor subtype and state specificity

Modulation of rhythmic brain activity by diazepam:GABAA receptor subtype and state specificity
Authors: C. Kopp, U. Rudolph, K. Lõw, e I. Tobler

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The inhibitory neurotransmitter -aminobutyric acid (GABA) is involved in the generation of various brain rhythmic activities that can be modulated by benzodiazepines. Here, we assessed the contribution of 2GABA type A (GABAA) receptors to the effects of benzodiazepines on sleep and waking oscillatory patterns by
combining pharmacological and genetic tools. The effects of diazepam on the electroencephalogram were compared between 2(H101R) knock-in mice in which the 2GABAA receptor was rendered diazepam-insensitive, and their wild-type controls. The suppression of delta activity typically induced by diazepam in
non-rapid eye movement (REM) sleep was significantly stronger in wild-type control mice than in 2(H101R) mice. Moreover, electroencephalogram frequency activity above 16–18 Hz was enhanced in wild-type mice both in non-REM sleep and waking. This effect was absent in 2(H101R) mice. Theta activity was enhanced after diazepam both in REM sleep and in waking in wild-type mice. In 2(H101R) mice, this effect was markedly reduced in REM sleep whereas it persisted in waking. These findings suggest that 2GABAA receptors, which are expressed in hypothalamic and pontine nuclei and in the hippocampus, are localized in distinct neural circuits relevant for the modulation of rhythmic brain activities by benzodiazepines.


sexta-feira, 11 de abril de 2014

Visual ecology of the Australian lungfish (Neoceratodus forsteri)

Visual ecology of the Australian lungfish (Neoceratodus forsteri)
Authors: Nathan S Hart, Helena J Bailes, Misha Vorobyev, N Justin Marshall & Shaun P Collin

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Abstract
Background: The transition from water to land was a key event in the evolution of vertebrates
that occurred over a period of 15–20 million years towards the end of the Devonian. Tetrapods,
including all land-living vertebrates, are thought to have evolved from lobe-finned (sarcopterygian)
fish that developed adaptations for an amphibious existence. However, while many of the
biomechanical and physiological modifications necessary to achieve this feat have been studied in
detail, little is known about the sensory adaptations accompanying this transition. In this study, we
investigated the visual system and visual ecology of the Australian lungfish Neoceratodus forsteri,
which is the most primitive of all the lungfish and possibly the closest living relative to the ancestors
of tetrapods.
Results: Juvenile Neoceratodus have five spectrally distinct retinal visual pigments. A single type of
rod photoreceptor contains a visual pigment with a wavelength of maximum absorbance (λmax) at
540 nm. Four spectrally distinct single cone photoreceptors contain visual pigments with λmax at
366 (UVS), 479 (SWS), 558 (MWS) and 623 nm (LWS). No double cones were found. Adult lungfish
do not possess UVS cones and, unlike juveniles, have ocular media that prevent ultraviolet light
from reaching the retina. Yellow ellipsoidal/paraboloidal pigments in the MWS cones and red oil
droplets in the LWS cones narrow the spectral sensitivity functions of these photoreceptors and
shift their peak sensitivity to 584 nm and 656 nm, respectively. Modelling of the effects of these
intracellular spectral filters on the photoreceptor colour space of Neoceratodus suggests that they
enhance their ability to discriminate objects, such as plants and other lungfishes, on the basis of
colour.
Conclusion: The presence of a complex colour vision system based on multiple cone types and
intracellular spectral filters in lungfishes suggests that many of the ocular characteristics seen in
terrestrial or secondarily aquatic vertebrates, such as birds and turtles, may have evolved in shallow
water prior to the transition onto land. Moreover, the benefits of spectral filters for colour
discrimination apply equally to purely aquatic species as well as semi-aquatic and terrestrial animals.
The visual system of the Australian lungfish resembles that of terrestrial vertebrates far more
closely than that of other sarcopterygian fish. This supports the idea that lungfishes, and not the
coelacanth, are the closest living relatives of the ancestors of tetrapods.


domingo, 30 de março de 2014

Evolution of the vertebrate eye: opsins, photoreceptors, retina and eye cup

Evolution of the vertebrate eye: opsins, photoreceptors, retina and eye cup
 
Authors: Trevor D. Lamb, Shaun P. Collin and Edward N. Pugh, Jr

Abstract
Charles Darwin appreciated the conceptual difficulty in accepting that an organ as wonderful as the vertebrate eye could have evolved through natural selection. He reasoned that if appropriate gradations could be found that were useful to the animal and were inherited, then the apparent difficulty would be overcome. Here, we review a wide range of findings that capture glimpses of the gradations that appear to have occurred during eye evolution, and provide a scenario for the unseen steps that have led to the emergence of the vertebrate eye.