Regulation of Higher Order Chromatin at GRIN2B and GAD1 Genetic Loci in Human and Mouse Brain: A Dissertation

Little is known about higher order chromatin structures in the human brain and their function in transcription regulation. We employed chromosome conformation capture (3C) to analyze chromatin architecture within 700 Kb surrounding the transcription start site (TSS) of the NMDA receptor and schizophrenia susceptibility gene, GRIN2B, in human and mouse cerebral cortex. Remarkably, both species showed a higher interaction between the TSS and an intronic sequence, enriched for (KRAB) Krueppel associated Box domain binding sites and selectively targeted by the (H3K9) histone 3 lysine 9 specific methyltransferase ESET/SETDB1. Transgenic mice brain cortical nuclei over-expressing Setdb1 showed increased heterochromatin-protein 1 signal at the interacting regions coupled with decreased Grin2b expression. 3C further revealed three long distant chromatin loop interactions enriched with functional enhancer specific (H3K27Ac) histone 3 lysine 27 acetylation signal in GRIN2B expressing tissue (human cortical nuclei and Human Embryonic Kidney - HEK cells). Doxycycline-induced SETDB1 over-expression decreased 2 out of 3 loop interaction frequencies suggesting a possible SETDB1-mediated transcription repression. We also report a specific looping interaction between a region 50Kb upstream of the (GAD1) Glutamic Acid Decarboxylase – 1 gene TSS and the GAD1 TSS in human brain nuclei. GAD1 catalyzes the rate limiting step in (GABA) gamma amino-butyric acid synthesis and is quintessential for inhibitory signaling in the human brain. Clinical studies in schizophrenia brain samples reveal a decreased looping interaction frequency in correspondence with a decrease in gene expression. Our findings provide evidence for the existence of transcription relevant higher order chromatin structures in human brain

Scoping technology options for India's oil security: Part I - ethanol for petrol

Crude oil prices recently crossed US$ 75/bbl, fuelling serious concerns whether India's rapidly expanding economy can sustain a high and growing level of crude imports. There are also serious concerns of global warming from burning of fossil fuels. It may be time for India to explore options which can substitute petrol and diesel and are climate-friendly. In a series of two articles, we examine a few such technology and policy options. Part I focus on options for substituting petrol by ethanol from sugarcane: molasses, sugarcane juice and cellulose (bagasse). Part II analyses options for diesel substitution: Fischer-Tropsch liquids from coal, and bio-diesel from oil-bearing plants like jatropha

Scoping technology options for India's oil security: Part II - Coal to liquids and bio-diesel

India's diesel consumption is several times that of petrol. In this article, we examine two options for meeting India"s diesel demand: coal to liquids and bio-diesel. Coal gasification, followed by Fischer- Tropsch (FT) synthesis offers an opportunity for large-scale production of diesel as proven by South Africa, and now being attempted by China and Qatar. India could consider this option given its large coal reserves. Four such plants consuming 60-76 million tonnes (mt) coal per annum can generate 12 mt of FT liquid, which is 20% of the expected diesel demand in 2011-12. This would require an investment of about Rs 54,000-90,000 crores. FT synthesis is a proven technology, coal prices are relatively stable and land requirements are modest. However, coal supply and transportation could be a concern and the process increases India's CO2 emissions by about 80 mt. Oil-bearing plants such as jatropha, palm and sunflower can be cultivated on wastelands to produce bio-diesel. This option has several advantages: it can be integrated with the rural economy, almost CO2 neutral and a large employment generation potential. However, it is a mammoth undertaking requiring an investment of about Rs 45,000-58,000 crores. We also briefly discuss the potential of energy conservation using gasoline-hybrid cars, which can potentially increase fuel efficiency up to 200 miles per gallon

Alveolar soft part sarcoma masquerading as lipoma: a case report

We report herein, a rare case of a 14-year-old child with alveolar soft part sarcoma. The patient initially noticed a progressively growing mass over medial side of right distal thigh. Although clinically the swelling appeared to be lipoma, the needle biopsy confirmed it to be alveolar soft part sarcoma. Patient was managed by wide excision, followed by adjuvant chemotherapy

Giant cell tumor distal end radius: resection and reconstruction using proximal fibular graft

Giant cell tumour forms 4% of all primary tumors. GCT distal radius is very rare. Current study presents a case of a 27 year female who was managed by wide excision and reconstruction with ipsilateral fibula. At one year follow up, patient had excellent range of motion at wrist joint and hand

DETECTING PACKET LOSS ON RTP STREAMS LEVERAGING CLOUD SCALE ASIC FLOW TABLES

A number of customers in, for example, the Service Provider segment, the Media and Entertainment industry, etc. use networks to transport audio and video signals. These audio and video signals include uncompressed video transported in accordance with the Society of Motion Picture and Television Engineers (SMPTE) ST 2110 standards, compressed video in accordance with the Moving Picture Experts Group (MPEG) standards, JPEG 2000 (J2K), etc., which may be User Datagram Protocol (UDP)/Real-time Transport Protocol (RTP) flows in a network. Today, when there is packet loss, end customers/operators find it very difficult to determine where the packet loss is happening in the network as, at times, the flows traverse different geographic regions, different service providers, etc. The techniques presented herein leverage flow tables on vendor Cloud Scale application-specific integrated circuits (ASICs) to detect gaps in RTP flows (i.e., to detect RTP packet drops). As soon as RTP packet drops are detected, the networking device (e.g., switch with the Cloud Scale ASIC) can generate an alert notifying the end customer/operator of the packet loss, thereby enabling the end customer/operator to pinpoint exactly where the loss is occurring

Does vitamin D3 supplementation improve medial joint space narrowing in patients with osteoarthritis knee

Background: Although vitamin D3 levels are known to improve pain and knee function in patients with knee OA, no clear evidence is available regarding relation between improvement in medial joint space with improvement in vitamin D3 levels. The aim of this study was to evaluate effectiveness of vitamin D3 supplements in improving joint space in the patients with OA knee.Methods: 100 patients with OA Knee who fulfilled inclusion criteria and consented to participate were enrolled for study. Patients of OA Knee were blinded and randomized to receive either tablet vitamin D3 or identical placebo tablet. Vitamin D3 Tab was administered in a dose of 60000U/week for 3 months in 12 doses while placebo tablets with identical dosing schedule were used for control group. The patients who received vitamin D3 tablets were allocated to case group while those receiving identical placebo tablets were grouped as controls. The vitamin D3 levels and medial joint space were assessed at baseline, 3 mo, 6mo and 1 year in both the groups.Results: In two groups of patients of OA knee of 50 patients each vitamin D3 supplementation increased levels of vitamin D3 in case group. While no significant improvement in joint space narrowing was noted with vitamin D3 supplementation in case group. Also no significant correlation was observed between vitamin D3 levels and medial joint space narrowing.Conclusions: There was no improvement in medial knee joint space with vitamin D3 supplementation

Phenomenology of the simplest linear seesaw mechanism

The linear seesaw mechanism provides a simple way to generate neutrino masses. In addition to Standard Model particles, it includes quasi-Dirac leptons as neutrino mass mediators, and a leptophilic scalar doublet seeding small neutrino masses. Here we review its associated physics, including restrictions from theory and phenomenology. The model yields potentially detectable $\mu\to e\gamma$ rates as well as distinctive signatures in the production and decay of heavy neutrinos ($N_i$) and the charged Higgs boson ($H^\pm$) arising from the second scalar doublet. We have found that production processes such as $e^+e^-\to NN$, $e^-\gamma\to NH^-$ and $e^+ e^-\to H^+ H^-$ followed by the decay chain $H^\pm\to\ell_i^\pm N$, $N\to \ell_j^{\pm}W^\mp$ leads to striking lepton number violation signatures at high energies which may probe the Majorana nature of neutrinos.Comment: 52 pages, 33 figures, 2 table

Heavy neutrino signatures from leptophilic Higgs portal in the linear seesaw

Lepton collider setups can probe the neutrino sector in the linear seesaw mechanism. Small neutrino masses are sourced by a tiny vacuum expectation value of a leptophilic scalar Higgs doublet and are mediated by Quasi-Dirac heavy neutrinos. These new particles can all be accessible to colliders. We describe novel charged Higgs and heavy neutrino production mechanisms that can be sizeable at $e^{+} e^{-}$ or $e^{-} {\gamma}$ colliders and discuss some of the associated signatures. These may shed light on the Majorana nature of neutrinos and the role of lepton number and lepton flavour symmetries.Comment: 10 pages, 4 figure

Setdb1 histone methyltransferase regulates mood-related behaviors and expression of the NMDA receptor subunit NR2B

Histone methyltransferases specific for the histone H3-lysine 9 residue, including Setdb1 (Set domain, bifurcated 1)/Eset/Kmt1e are associated with repressive chromatin remodeling and expressed in adult brain, but potential effects on neuronal function and behavior remain unexplored. Here, we report that transgenic mice with increased Setdb1 expression in adult forebrain neurons show antidepressant-like phenotypes in behavioral paradigms for anhedonia, despair, and learned helplessness. Chromatin immunoprecipitation in conjunction with DNA tiling arrays (ChIP-chip) revealed that genomic occupancies of neuronal Setdb1 are limited t