18520 Via Princessa Suite C-2
Canyon Country CA 91387
Medical School: Other - Unknown
Accepts Medicare: No
Participates In eRX: No
Participates In PQRS: No
Participates In EHR: No
License #: DC26487
Request Appointment Information
Awards & Recognitions
Medical Malpractice Cases
Medical Board Sanctions
Reprogramming of pericyte-derived cells of the adult human brain into induced neuronal cells. - Cell stem cell
Reprogramming of somatic cells into neurons provides a new approach toward cell-based therapy of neurodegenerative diseases. A major challenge for the translation of neuronal reprogramming into therapy is whether the adult human brain contains cell populations amenable to direct somatic cell conversion. Here we show that cells from the adult human cerebral cortex expressing pericyte hallmarks can be reprogrammed into neuronal cells by retrovirus-mediated coexpression of the transcription factors Sox2 and Mash1. These induced neuronal cells acquire the ability of repetitive action potential firing and serve as synaptic targets for other neurons, indicating their capability of integrating into neural networks. Genetic fate-mapping in mice expressing an inducible Cre recombinase under the tissue-nonspecific alkaline phosphatase promoter corroborated the pericytic origin of the reprogrammed cells. Our results raise the possibility of functional conversion of endogenous cells in the adult human brain to induced neuronal fates.Copyright Â© 2012 Elsevier Inc. All rights reserved.
Generation of subtype-specific neurons from postnatal astroglia of the mouse cerebral cortex. - Nature protocols
Instructing glial cells to generate neurons may prove to be a strategy to replace neurons that have degenerated. Here, we describe a robust protocol for the efficient in vitro conversion of postnatal astroglia from the mouse cerebral cortex into functional, synapse-forming neurons. This protocol involves two steps: (i) expansion of astroglial cells (7 d) and (ii) astroglia-to-neuron conversion induced by persistent and strong retroviral expression of Neurog2 (encoding neurogenin-2) or Mash1 (also referred to as achaete-scute complex homolog 1 or Ascl1) and/or distal-less homeobox 2 (Dlx2) for generation of glutamatergic or GABAergic neurons, respectively (7-21 d for different degrees of maturity). Our protocol of astroglia-to-neuron conversion by a single neurogenic transcription factor provides a stringent experimental system to study the specification of a selective neuronal subtype, thus offering an alternative to the use of embryonic or neural stem cells. Moreover, it can be a useful model for studies of lineage conversion from non-neuronal cells, with potential for brain regenerative medicine.
Neuronal network formation from reprogrammed early postnatal rat cortical glial cells. - Cerebral cortex (New York, N.Y. : 1991)
In the subependymal zone and the dentate gyrus of the adult brain of rodents, neural stem cells with glial properties generate new neurons in a life-long process. The identification of glial progenitors outside the neurogenic niches, oligodendrocyte precursors in the healthy brain, and reactive astrocytes after cortical injury led to the idea of using these cells as endogenous cell source for neural repair in the cerebral cortex. Recently, our group showed that proliferating astroglia from the cerebral cortex can be reprogrammed into neurons capable of action potential firing by forced expression of neurogenic fate determinants but failed to develop synapses. Here, we describe a maturation profile of cultured reprogrammed NG2+ and glial fibrillary acidic protein+ glia cells of the postnatal rat cortex that ends with the establishment of a glutamatergic neuronal network. Within 3 weeks after viral expression of the transcription factor neurogenin 2 (Ngn2), glia-derived neurons exhibit network-driven, glutamate receptor-dependent oscillations in Ca(2+) and exhibit functional pre- and postsynaptic specialization. Interestingly, the Ngn2-instructed glutamatergic network also supports the maturation of a Î³-aminobutyric acid (GABA)ergic input via GABA(A) receptors in a non-cell autonomous manner. The "proof-of-principle" results imply that a single transcription factor may be sufficient to instruct a neuronal network from a glia-like cell source.
Directing astroglia from the cerebral cortex into subtype specific functional neurons. - PLoS biology
Astroglia from the postnatal cerebral cortex can be reprogrammed in vitro to generate neurons following forced expression of neurogenic transcription factors, thus opening new avenues towards a potential use of endogenous astroglia for brain repair. However, in previous attempts astroglia-derived neurons failed to establish functional synapses, a severe limitation towards functional neurogenesis. It remained therefore also unknown whether neurons derived from reprogrammed astroglia could be directed towards distinct neuronal subtype identities by selective expression of distinct neurogenic fate determinants. Here we show that strong and persistent expression of neurogenic fate determinants driven by silencing-resistant retroviral vectors instructs astroglia from the postnatal cortex in vitro to mature into fully functional, synapse-forming neurons. Importantly, the neurotransmitter fate choice of astroglia-derived neurons can be controlled by selective expression of distinct neurogenic transcription factors: forced expression of the dorsal telencephalic fate determinant neurogenin-2 (Neurog2) directs cortical astroglia to generate synapse-forming glutamatergic neurons; in contrast, the ventral telencephalic fate determinant Dlx2 induces a GABAergic identity, although the overall efficiency of Dlx2-mediated neuronal reprogramming is much lower compared to Neurog2, suggesting that cortical astroglia possess a higher competence to respond to the dorsal telencephalic fate determinant. Interestingly, however, reprogramming of astroglia towards the generation of GABAergic neurons was greatly facilitated when the astroglial cells were first expanded as neurosphere cells prior to transduction with Dlx2. Importantly, this approach of expansion under neurosphere conditions and subsequent reprogramming with distinct neurogenic transcription factors can also be extended to reactive astroglia isolated from the adult injured cerebral cortex, allowing for the selective generation of glutamatergic or GABAergic neurons. These data provide evidence that cortical astroglia can undergo a conversion across cell lineages by forced expression of a single neurogenic transcription factor, stably generating fully differentiated neurons. Moreover, neuronal reprogramming of astroglia is not restricted to postnatal stages but can also be achieved from terminally differentiated astroglia of the adult cerebral cortex following injury-induced reactivation.
Nanoparticle charge control in nonpolar liquids: insights from small-angle neutron scattering and microelectrophoresis. - Langmuir : the ACS journal of surfaces and colloids
Electrostatic forces are typically produced in low polarity solvents by the addition of surfactants or charge-control additives. Although widely used, there is no consensus on the mechanism by which surfactants control the level of particle charge. We report an investigation using highly sensitive, single particle optical microelectrophoresis measurements combined with a small-angle neutron scattering study to establish the mechanism of charging by the surfactant AOT in the nonpolar solvent n-dodecane. We show that polymer-grafted particles with no chemically bound surface charges only charge above the critical micellar concentration of the surfactant. The surface potential increases gradually with increasing surfactant concentration c, before finally saturating at high c. The increase in the surface potential is correlated to the amount of surfactant adsorbed onto the surface of the particle. Using deuterated AOT and contrast variation techniques, we demonstrate that the surfactant is adsorbed within the polymer layer surrounding the particle core, probably as individual molecules rather than surfactant aggregates. A simple thermodynamic model accounts for the concentration dependence of the observed surface potential.
Widespread distribution of a newly found point mutation in voltage-gated sodium channel in pyrethroid-resistant Aedes aegypti populations in Vietnam. - PLoS neglected tropical diseases
Resistance of Aedes aegypti to photostable pyrethroid insecticides is a major problem for disease-vector control programs. Pyrethroids target the voltage-gated sodium channel on the insects' neurons. Single amino acid substitutions in this channel associated with pyrethroid resistance are one of the main factors that cause knockdown resistance in insects. Although kdr has been observed in several mosquito species, point mutations in the para gene have not been fully characterized in Ae. aegypti populations in Vietnam. The aim of this study was to determine the types and frequencies of mutations in the para gene in Ae. aegypti collected from used tires in Vietnam.Several point mutations were examined that cause insensitivity of the voltage-gated sodium channel in the insect nervous system due to the replacement of the amino acids L1014F, the most commonly found point mutation in several mosquitoes; I1011M (or V) and V1016G (or I), which have been reported to be associated to knockdown resistance in Ae. aegypti located in segment 6, domain II; and a recently found amino acid replacement in F1269 in Ae. aegypti, located in segment 6, domain III. Among 756 larvae from 70 locations, no I1011M or I1011V nor L1014F mutations were found, and only two heterozygous V1016G mosquitoes were detected. However, F1269C mutations on domain III were distributed widely and with high frequency in 269 individuals among 757 larvae (53 collection sites among 70 locations surveyed). F1269C frequencies were low in the middle to north part of Vietnam but were high in the areas neighboring big cities and in the south of Vietnam, with the exception of the southern mountainous areas located at an elevation of 500-1000 m.The overall percentage of homozygous F1269C seems to remain low (7.4%) in the present situation. However, extensive and uncontrolled frequent use of photostable pyrethroids might be a strong selection pressure for this mutation to cause serious problems in the control of dengue fever in Vietnam.
Genetic ablation of FLRT3 reveals a novel morphogenetic function for the anterior visceral endoderm in suppressing mesoderm differentiation. - Genes & development
During early mouse development, the anterior visceral endoderm (AVE) secretes inhibitor and activator signals that are essential for establishing the anterior-posterior (AP) axis of the embryo and for restricting mesoderm formation to the posterior epiblast in the primitive streak (PS) region. Here we show that AVE cells have an additional morphogenetic function. These cells express the transmembrane protein FLRT3. Genetic ablation of FLRT3 did not affect the signaling functions of the AVE according to the normal expression pattern of Nodal and Wnt and the establishment of a proper AP patterning in the epiblast. However, FLRT3(-/-) embryos showed a highly disorganized basement membrane (BM) in the AVE region. Subsequently, adjacent anterior epiblast cells displayed an epithelial-to-mesenchymal transition (EMT)-like process characterized by the loss of cell polarity, cell ingression, and the up-regulation of the EMT and the mesodermal marker genes Eomes, Brachyury/T, and FGF8. These results suggest that the AVE acts as a morphogenetic boundary to prevent EMT and mesoderm induction in the anterior epiblast by maintaining the integrity of the BM. We propose that this novel function cooperates with the signaling activities of the AVE to restrict EMT and mesoderm induction to the posterior epiblast.
Electrostatic charging of nonpolar colloids by reverse micelles. - Langmuir : the ACS journal of surfaces and colloids
Colloids dispersed in a nonpolar solvent become charged when reverse micelles are added. We study the charge of individual sterically stabilized poly(methyl methacrylate) spheres dispersed in micellar solutions of the surfactants sodium bis(2-ethyl 1-hexyl) sulfosuccinate [AOT], zirconyl 2-ethyl hexanoate [Zr(Oct)2], and a copolymer of poly(12-hydroxystearic acid)-poly(methyl methacrylate) [PHSA-PMMA]. Although the sign of the particle charge is positive for Zr(Oct)2, negative for AOT, and essentially neutral for PHSA-PMMA, the different micellar systems display a number of common features. In particular, we demonstrate that over a wide range of concentrations the particle potential is a constant, independent of the number of micelles added and independent of the colloid size. A simple thermodynamic model, in which the particle charge is generated by the competitive adsorption of both positive and negative micelles, is in good agreement with the experimental data.
4,5,6-Triamino-2-(methylsulfanyl)pyrimidine: pi-stacked hydrogen-bonded sheets of R2/2(8), R2/2(10) and R6/6(32) rings. - Acta crystallographica. Section C, Crystal structure communications
In the title compound, C5H9N5S, the three independent C-NH2 units are all somewhat pyramidal. The molecules are linked by a combination of one N-H...S and two N-H...N hydrogen bonds into sheets containing three types of ring motif, viz. R(2)(2)(8), R(2)(2)(10) and R(6)(6)(32), all of them centrosymmetric. Adjacent sheets are linked by a single pi-pi stacking interaction.
Does cancer research focus on areas of importance to patients? - Ecancermedicalscience
The majority of research ideas are proposed by clinicians or scientists and little is currently known about which areas of research patients feel are important. We performed a 4 week pilot patient survey at the Royal Marsden (a specialist cancer centre) to investigate patients' views on priorities for cancer research. A total of 780 patients completed the survey and the top research priorities were identified as: detection and prevention of cancer, scientific understanding, curative treatment and personalised treatment. The top research priorities were remarkably consistent across age, gender and a variety of tumour types. We believe that patients' views should be considered alongside those of clinicians and researchers when devising research proposals and strategies.
Map & Directions
18520 Via Princessa Suite C-2 Canyon Country, CA 91387
17909 Soledad Canyon Rd
16622 Soledad Canyon Rd
17909 Soledad Canyon Rd
18520 Via Princessa Suite C-2
Santa Clarita, CA 91387
18500 Via Princessa Suite 1
Santa Clarita, CA 91387