Characterization of Bipolar Disorder Patient-Specific Induced Pluripotent Stem Cells from a Family Reveals Neurodevelopmental and mRNA Expression Abnormalities

Bipolar disorder (BD) is a common neuropsychiatric disorder characterized by chronic recurrent episodes of depression and mania. Despite evidence for high heritability of BD, little is known about its underlying pathophysiology. To develop new tools for investigating the molecular and cellular basis of BD we applied a family-based paradigm to derive and characterize a set of 12 induced pluripotent stem cell (iPSC) lines from a quartet consisting of two BD-affected brothers and their two unaffected parents. Initially, no significant phenotypic differences were observed between iPSCs derived from the different family members. However, upon directed neural differentiation we observed that CXCR4 (CXC chemokine receptor-4) expressing central nervous system (CNS) neural progenitor cells (NPCs) from both BD patients compared to their unaffected parents exhibited multiple phenotypic differences at the level of neurogenesis and expression of genes critical for neuroplasticity, including WNT pathway components and ion channel subunits. Treatment of the CXCR4+ NPCs with a pharmacological inhibitor of glycogen synthase kinase 3 (GSK3), a known regulator of WNT signaling, was found to rescue a progenitor proliferation deficit in the BD-patient NPCs. Taken together, these studies provide new cellular tools for dissecting the pathophysiology of BD and evidence for dysregulation of key pathways involved in neurodevelopment and neuroplasticity. Future generation of additional iPSCs following a family-based paradigm for modeling complex neuropsychiatric disorders in conjunction with in-depth phenotyping holds promise for providing insights into the pathophysiological substrates of BD and is likely to inform the development of targeted therapeutics for its treatment and ideally prevention

Exopolisacáridos bacterianos obtenidos desde hábitat marino extremo del Océano Antártico: Producción y caracterización parcial

Deep marine microorganisms survive under extreme ecological settings and harsh environmental conditions of low temperature, high salinity, and high atmospheric pressure making it significant of scientific interest. Southern Ocean (SO) is one such example of deep marine ecosystem and the microorganisms inhabiting in such hostile environment may produce different bioactive secondary metabolites. SO (Indian Sector) is relatively less documented in terms of microbial composition and community dynamics. The present study involves isolation of exopolysaccharides (EPSs) from three potent SO (Indian Sector) bacteria, optimization of the EPS production and partial characterization of them. Three different EPSs show varying structural conformation, that is from porous to strong flakes mimicking polymeric structure with C/N ratio ranging between 4 - 11. FTIR spectra have exhibited the presence of different active groups of carbohydrate moieties, water molecules and protein-associated amides. EPSs produced by marine microorganisms show high biotechnological promises such as drug carrier in pharmaceutical field, emulsifier and cryo protectant in food-processing industry, detoxification of petrochemical oils and much more. The three bacterial isolates in this study showed potential of producing EPS biopolymer that can be further explored in terms of its proper biotechnological applications.Los microorganismos marinos de zonas profundas sobreviven en entornos ecológicos extremos y condiciones ambientales adversas de baja temperatura, alta salinidad y alta presión atmosférica, lo que los hace tener un interés científico particularmente significativo. El Océano Antártico, es uno de esos ejemplos de ecosistemas marino profundo, y los microorganismos que habitan en ese ambiente hostil pueden producir diferentes metabolitos secundarios bioactivos. El Océano Antártico (sector indio) está relativamente menos documentado en términos de composición microbiana y dinámica comunitaria. El presente estudio consiste en el aislamiento de los exopolisacáridos (EPS) de tres potentes bacterias del Océano Antártico (sector indio), la optimización de la producción de EPS y la caracterización parcial de los mismos. Tres EPS diferentes muestran una conformación estructural variable, es decir, de copos porosos a fuertes que imitan la estructura polimérica con una relación C/N que oscila entre 4 y 11. Los espectros FTIR han exhibido la presencia de diferentes grupos activos de macromoléculas de carbohidratos, moléculas de agua y amidas asociadas a proteínas. Los EPS producidos por microorganismos marinos muestran un alto potencial biotecnológico, como transportador de drogas en el campo farmacéutico, emulsionante y crioprotector, todos ellos en la industria de procesamiento de alimentos, desintoxicación de aceites petroquímicos y mucho más. Los tres aislamientos bacterianos de este estudio mostraron potencial de producción de biopolímeros de EPS que pueden ser explorados más a fondo en términos de sus aplicaciones biotecnológicas adecuadas

Interplay between Gating and Block of Ligand-Gated Ion Channels

Drugs that inhibit ion channel function by binding in the channel and preventing current flow, known as channel blockers, can be used as powerful tools for analysis of channel properties. Channel blockers are used to probe both the sophisticated structure and basic biophysical properties of ion channels. Gating, the mechanism that controls the opening and closing of ion channels, can be profoundly influenced by channel blocking drugs. Channel block and gating are reciprocally connected; gating controls access of channel blockers to their binding sites, and channel-blocking drugs can have profound and diverse effects on the rates of gating transitions and on the stability of channel open and closed states. This review synthesizes knowledge of the inherent intertwining of block and gating of excitatory ligand-gated ion channels, with a focus on the utility of channel blockers as analytic probes of ionotropic glutamate receptor channel function

Magnetocaloric effect in textured rare earth intermetallic compound ErNi

Melt-spun ErNi crystallizes in orthorhombic FeB-type structure (Space group Pnma, no. 62) similar to the arc-melted ErNi compound. Room temperature X-ray diffraction (XRD) experiments reveal the presence of texture and preferred crystal orientation in the melt-spun ErNi. The XRD data obtained from the free surface of the melt-spun ErNi show large intensity enhancement for (1 0 2) Bragg reflection. The scanning electron microscopy image of the free surface depicts a granular microstructure with grains of ∼1 μm size. The arc-melted and the melt-spun ErNi compounds order ferromagnetically at 11 K and 10 K (TC) respectively. Field dependent magnetization (M-H) at 2 K shows saturation behaviour and the saturation magnetization value is 7.2 μB/f.u. for the arc-melted ErNi and 7.4 μB/f.u. for the melt-spun ErNi. The isothermal magnetic entropy change (ΔSm) close to TC has been calculated from the M-H data. The maximum isothermal magnetic entropy change, -ΔSmmax, is ∼27 Jkg-1K-1 and ∼24 Jkg-1K-1 for the arc-melted and melt-spun ErNi for 50 kOe field change, near TC. The corresponding relative cooling power values are ∼440 J/kg and ∼432 J/kg respectively. Although a part of ΔSm is lost to crystalline electric field (CEF) effects, the magnetocaloric effect is substantially large at 10 K, thus rendering melt-spun ErNi to be useful in low temperature magnetic refrigeration applications such as helium gas liquefaction

MeCP2 is critical for maintaining mature neuronal networks and global brain anatomy during late stages of postnatal brain development and in the mature adult brain

Mutations in the X-linked gene, methyl-CpG binding protein 2 (Mecp2), underlie a wide range of neuropsychiatric disorders, most commonly, Rett Syndrome (RTT), a severe autism spectrum disorder that affects approximately one in 10,000 female live births. Because mutations in the Mecp2 gene occur in the germ cells with onset of neurological symptoms occurring in early childhood, the role of MeCP2 has been ascribed to brain maturation at a specific developmental window. Here, we show similar kinetics of onset and progression of RTT-like symptoms in mice, including lethality, if MeCP2 is removed postnatally during the developmental stage that coincides with RTT onset, or adult stage. For the first time, we show that brains that lose MeCP2 at these two different stages are actively shrinking, resulting in higher than normal neuronal cell density. Furthermore, we show that mature dendritic arbors of pyramidal neurons are severely retracted and dendritic spine density is dramatically reduced. In addition, hippocampal astrocytes have significantly less complex ramified processes. These changes accompany a striking reduction in the levels of several synaptic proteins, including CaMKII α/β, AMPA, and NMDA receptors, and the synaptic vesicle proteins Vglut and Synapsin, which represent critical modifiers of synaptic function and dendritic arbor structure. Importantly, the mRNA levels of these synaptic proteins remains unchanged, suggesting that MeCP2 likely regulates these synaptic proteins post-transcriptionally, directly or indirectly. Our data suggest a crucial role for MeCP2 in post-transcriptional regulation of critical synaptic proteins involved in maintaining mature neuronal networks during late stages of postnatal brain development. © 2012 the authors

A Clinical Study of Dermatoses in Diabetes to Establish its Markers

Background: Cutaneous manifestations of diabetes mellitus generally appear subsequent to the development of the disease, but they may be the first presenting signs and in some cases they may precede the primary disease manifestation by many years. Aims : T0 he aim of our study was to study the spectrum of dermatoses in diabetics, to know the frequency of dermatoses specific to diabetes mellitus (DM), and to establish the mucocutaneous markers of DM. Material and Methods: The study was conducted at a diabetic clinic and our department between September 2008 and June 2010. Two hundred and twenty-four diabetic patients were included in the study group and those with gestational diabetes were excluded. Healthy age- and sex-matched individuals were taken as controls. Results: The male to female ratio was 1 : 1.21. Type 2 DM was seen in 89.7% and type 1 DM in 10.3% of the patients. Dermatoses were seen in 88.3% of the diabetics compared to 36% in non-diabetic controls (P<0.05). Cutaneous infections were the most common dermatoses followed by acanthosis nigricans and xerosis in diabetics. Type 2 DM was found to have an increased risk of complications than type 1 DM. Complications of diabetes were seen in 43.7% of the diabetic cases. Diabetic dermopathy, loss of hair over the legs, diabetic foot ulcer, and so on, were found to be the cutaneous markers of DM in our group of cases. Conclusion: Dermatoses were more common in diabetics than non-diabetics. Cutaneous infections formed the largest group of dermatoses in DM