A constitutively active Gαi3 protein corrects the abnormal retinal pigment epithelium phenotype of Oa1-/- mice.

PurposeOcular Albinism type 1 (OA1) is a disease caused by mutations in the OA1 gene and characterized by the presence of macromelanosomes in the retinal pigment epithelium (RPE) as well as abnormal crossing of the optic axons at the optic chiasm. We showed in our previous studies in mice that Oa1 activates specifically Gαi3 in its signaling pathway and thus, hypothesized that a constitutively active Gαi3 in the RPE of Oa1-/- mice might keep on the Oa1 signaling cascade and prevent the formation of macromelanosomes. To test this hypothesis, we have generated transgenic mice that carry the constitutively active Gαi3 (Q204L) protein in the RPE of Oa1-/- mice and are now reporting the effects that the transgene produced on the Oa1-/- RPE phenotype.MethodsTransgenic mice carrying RPE-specific expression of the constitutively active Gαi3 (Q204L) were generated by injecting fertilized eggs of Oa1-/- females with a lentivirus containing the Gαi3 (Q204L) cDNA. PCR, Southern blots, Western blots and confocal microscopy were used to confirm the presence of the transgene in the RPE of positive transgenic mice. Morphometrical analyses were performed using electron microscopy to compare the size and number of melanosomes per RPE area in putative Oa1-/-, Gαi3 (Q204L) transgenic mice with those of wild-type NCrl and Oa1-/- mice.ResultsWe found a correlation between the presence of the constitutively active Gαi3 (Q204L) transgene and the rescue of the normal phenotype of RPE melanosomes in Oa1-/-, Gαi3 (Q204L) mice. These mice have higher density of melanosomes per RPE area and a larger number of small melanosomes than Oa1-/- mice, and their RPE phenotype is similar to that of wild-type mice.ConclusionsOur results show that a constitutively active Gαi3 protein can by-pass the lack of Oa1 protein in Oa1-/- mice and consequently rescue the RPE melanosomal phenotype

Giα proteins exhibit functional differences in the activation of ERK1/2, Akt and mTORC1 by growth factors in normal and breast cancer cells

Background In a classic model, Giα proteins including Gi1α, Gi2α and Gi3α are important for transducing signals from Giα protein-coupled receptors (GiαPCRs) to their downstream cascades in response to hormones and neurotransmitters. Our previous study has suggested that Gi1α, Gi2α and Gi3α are also important for the activation of the PI3K/Akt/mTORC1 pathway by epidermal growth factor (EGF) and its family members. However, a genetic role of these Giα proteins in the activation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) by EGF is largely unknown. Further, it is not clear whether these Giα proteins are also engaged in the activation of both the Akt/mTORC1 and ERK1/2 pathways by other growth factor family members. Additionally, a role of these Giα proteins in breast cancer remains to be elucidated. Results We found that Gi1/3 deficient MEFs with the low expression level of Gi2α showed defective ERK1/2 activation by EGFs, IGF-1 and insulin, and Akt and mTORC1 activation by EGFs and FGFs. Gi1/2/3 knockdown breast cancer cells exhibited a similar defect in the activations and a defect in in vitro growth and invasion. The Giα proteins associated with RTKs, Gab1, FRS2 and Shp2 in breast cancer cells and their ablation impaired Gab1’s interactions with Shp2 in response to EGF and IGF-1, or with FRS2 and Grb2 in response to bFGF. Conclusions Giα proteins differentially regulate the activation of Akt, mTORC1 and ERK1/2 by different families of growth factors. Giα proteins are important for breast cancer cell growth and invasion.Fil: Wang, Zhanwei. University of Hawaii Cancer Center. Honolulu; Estados UnidosFil: Dela Cruz, Rica. University of Hawaii Cancer Center. Honolulu; Estados UnidosFil: Ji, Fang. Shanghai Jiao Tong University . Sahnghai; ChinaFil: Guo, Sheng. University of Hawaii Cancer Center. Honolulu; Estados Unidos. Shanghai Jiaotong University. Shangha; Estados UnidosFil: Zhang, Jianhua. Shanghai Jiaotong University. Shangha; Estados Unidos. University of Hawaii Cancer Center. Honolulu; Estados UnidosFil: Wang, Ying. David Geffen School of Medicine at UCLA. Los Angeles; Estados UnidosFil: Feng, Gen-Sheng. University of California at San Diego; Estados UnidosFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institutes of Health; Estados UnidosFil: Jiang, Meisheng. David Geffen School of Medicine at UCLA. Los Angeles; Estados UnidosFil: Chu, Wen Ming. University of Hawaii Cancer Center. Honolulu; Estados Unido

Biofeedback EEG can quantify abnormal phenomenon of EEG in psychology

TEEG (electroencephalography, EEG) is a kind of single which we know human brain function active.BT (Biofeedback Therapy, BT) is based the method of EEG technology, focusing on the studies of human thoughts and emotions activities. We shall study new points that the two kinds of EEG technology are used simultaneously, to find the BT can be quantified abnormal EEG activities in mental illness, to provide the certain reference value in clinical. We found that BT can quantify β wave, θ wave and some abnormal phenomenon of traditional EEG. Therefore, based on the conventional examination of the traditional EEG in clinical, we used BT to further check. The results show not only to quantify the advantages of traditional EEG brain waves specific values occur, such as the specific data of fatigue (θ wave) and anxiety (β wave), but also abnormal phenomenon. Quantized data would become more intuitive, and to assess the clinical efficacy of treatment more scientific and objectivity

c-Met-Dependent Multipotent Labyrinth Trophoblast Progenitors Establish Placental Exchange Interface

SummaryThe placenta provides the interface for gas and nutrient exchange between the mother and the fetus. Despite its critical function in sustaining pregnancy, the stem/progenitor cell hierarchy and molecular mechanisms responsible for the development of the placental exchange interface are poorly understood. We identified an Epcamhi labyrinth trophoblast progenitor (LaTP) in mouse placenta that at a clonal level generates all labyrinth trophoblast subtypes, syncytiotrophoblasts I and II, and sinusoidal trophoblast giant cells. Moreover, we discovered that hepatocyte growth factor/c-Met signaling is required for sustaining proliferation of LaTP during midgestation. Loss of trophoblast c-Met also disrupted terminal differentiation and polarization of syncytiotrophoblasts, leading to intrauterine fetal growth restriction, fetal liver hypocellularity, and demise. Identification of this c-Met-dependent multipotent LaTP provides a landmark in the poorly defined placental stem/progenitor cell hierarchy and may help us understand pregnancy complications caused by a defective placental exchange

Molecular Mechanisms of Go Signaling

Go is the most abundant G protein in the central nervous system, where it comprises about 1% of membrane protein in mammalian brains. It functions to couple cell surface receptors to intercellular effectors, which is a critical process for cells to receive, interpret and respond to extracellular signals. Go protein belongs to the pertussis toxin-sensitive Gi/Go subfamily of G proteins. A number of G-protein-coupled receptors transmit stimuli to intercellular effectors through Go. Go regulates several cellular effectors, including ion channels, enzymes, and even small GTPases to modulate cellular function. This review summarizes some of the advances in Go research and proposes areas to be further addressed in exploring the functional role of Go

A constitutively active Gαi3 protein corrects the abnormal retinal pigment epithelium phenotype of Oa1-/- mice.

PurposeOcular Albinism type 1 (OA1) is a disease caused by mutations in the OA1 gene and characterized by the presence of macromelanosomes in the retinal pigment epithelium (RPE) as well as abnormal crossing of the optic axons at the optic chiasm. We showed in our previous studies in mice that Oa1 activates specifically Gαi3 in its signaling pathway and thus, hypothesized that a constitutively active Gαi3 in the RPE of Oa1-/- mice might keep on the Oa1 signaling cascade and prevent the formation of macromelanosomes. To test this hypothesis, we have generated transgenic mice that carry the constitutively active Gαi3 (Q204L) protein in the RPE of Oa1-/- mice and are now reporting the effects that the transgene produced on the Oa1-/- RPE phenotype.MethodsTransgenic mice carrying RPE-specific expression of the constitutively active Gαi3 (Q204L) were generated by injecting fertilized eggs of Oa1-/- females with a lentivirus containing the Gαi3 (Q204L) cDNA. PCR, Southern blots, Western blots and confocal microscopy were used to confirm the presence of the transgene in the RPE of positive transgenic mice. Morphometrical analyses were performed using electron microscopy to compare the size and number of melanosomes per RPE area in putative Oa1-/-, Gαi3 (Q204L) transgenic mice with those of wild-type NCrl and Oa1-/- mice.ResultsWe found a correlation between the presence of the constitutively active Gαi3 (Q204L) transgene and the rescue of the normal phenotype of RPE melanosomes in Oa1-/-, Gαi3 (Q204L) mice. These mice have higher density of melanosomes per RPE area and a larger number of small melanosomes than Oa1-/- mice, and their RPE phenotype is similar to that of wild-type mice.ConclusionsOur results show that a constitutively active Gαi3 protein can by-pass the lack of Oa1 protein in Oa1-/- mice and consequently rescue the RPE melanosomal phenotype