Differential effects of cholesterol and 7-dehydrocholesterol on the ligand binding activity of the hippocampal serotonin<SUB>1A</SUB> receptor: implications in SLOS

The requirement of membrane cholesterol in maintaining ligand binding activity of the hippocampal serotonin1A receptor has previously been demonstrated. In order to test the stringency of the requirement of cholesterol, we depleted cholesterol from native hippocampal membranes followed by replenishment with 7-dehydrocholesterol. The latter sterol is an immediate biosynthetic precursor of cholesterol differing only in a double bond at the 7th position in the sterol ring. Our results show, for the first time, that replenishment with 7-dehydrocholesterol does not restore ligand binding activity of the serotonin1A receptor, in spite of recovery of the overall membrane order. The requirement for restoration of ligand binding activity therefore is more stringent than the requirement for the recovery of overall membrane order. These novel results have potential implications in understanding the interaction of membrane lipids with this important neuronal receptor under pathogenic conditions such as the Smith-Lemli-Opitz syndrome

Differential effects of cholesterol and 7-dehydrocholesterol on ligand binding of solubilized hippocampal serotonin<SUB>1A</SUB> receptors: implications in SLOS

The serotonin1A receptor is an important member of the G-protein coupled receptor family, and is involved in the generation and modulation of a variety of cognitive, behavioral, and developmental functions. Solubilization of the hippocampal serotonin1A receptor by 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS) is accompanied by loss of membrane cholesterol which results in a reduction in specific agonist binding activity. Replenishment of cholesterol to solubilized membranes restores the cholesterol content of the membrane and significantly enhances specific agonist binding activity. In order to test the stringency of the requirement of cholesterol in this process, we solubilized native hippocampal membranes followed by replenishment with 7-dehydrocholesterol (7-DHC). 7-DHC is an immediate biosynthetic precursor of cholesterol differing only in a double bond at the 7th position in its sterol ring. Our results show, for the first time, that replenishment of solubilized hippocampal membranes with 7-DHC does not restore ligand binding activity of the serotonin1A receptor, in spite of recovery of the overall membrane order. This observation shows that the requirement for restoration of ligand binding activity is more stringent than the requirement for the recovery of overall membrane order. These novel results have potential implications in understanding the interaction of membrane sterols with this important neuronal receptor under pathogenic conditions such as the Smith-Lemli-Opitz syndrome

Six-membered ring systems: with O and/or S atoms

A large variety of publications have emerged in 2012 involving O- and S-6- membered ring systems. The increasing number of reviews and other communica- tions dedicated to natural and synthetic derivatives and their biological significance highlights the importance of these heterocycles. Reviews on natural products involve biosynthesis and isolation of enantiomeric derivatives h12AGE4802i, biosynthesis, isolation, synthesis, and biological studies on the pederin family h12NPR980i and xanthones obtained from fungi, lichens, and bacteria h12CR3717i and on the potential chemotherapeutic value of phyto- chemical products and plant extracts as antidiabetic h12NPR580i, antimicrobial, and resistance-modifying agents h12NPR1007i. A more specific review covers a structure–activity relationship of endoperoxides from marine origin and their antitry- panosomal activity h12OBC7197i. New synthetic routes to naturally occurring, biologically active pyran derivatives have been the object of several papers. Different approaches have been discussed for the total synthesis of tetrahydropyran-containing natural products (")-zampanolide h12CEJ16868, 12EJO4130, 12OL3408i, (")-aspergillides A and B h12H(85)587, 12H(85)1255, 12TA252i, (þ)-neopeltolide h12JOC2225, 12JOC9840, 12H(85) 1255i, or their macrolactone core h12OBC3689, 12OL2346i. The total synthesis of bistramide A h12CEJ7452i and (þ)-kalihinol A h12CC901i and the stereoselec- tive synthesis of a fragment of bryostatin h12S3077, 12TL6163i have also been sur- veyed. Other papers relate the total synthesis of naturally occurring carbocyclic and heterocyclic-fused pyran compounds, such as (")-dysiherbaine h12CC6295i, penos- tatin B h12OL244i, Greek tobacco lactonic products, and analogues h12TL4293i and on the structurally intriguing limonoids andhraxylocarpins A–E h12CEJ14342i. The stereocontrolled synthesis of fused tetrahydropyrans was used in the preparation of blepharocalyxin D h12AGE3901i. Polyphenolic heterocyclic compounds have also received great attention in 2012. The biological activities and the chemistry of prenylated caged xanthones h12PCB78i, the occurrence of sesquiterpene coumarins h12PR77i, and the medicinal properties of the xanthone mangiferin h12MRME412i have been reviewed. An overview on the asymmetric syntheses of flavanones and chromanones h12EJO449i, on the synthesis and reactivity of flavones h12T8523i and xanthones h12COC2818i, on the synthesis and biosynthesis of biocoumarins h12T2553i, and on the synthesis and applications of flavylium compounds h12CSR869i has been discussed. The most recent developments in the synthesis and applications of sultones, a very important class of sulfur compounds, were reported h12CR5339i. A review on xanthene-based fluorescent probes for sensing cations, anions, bio- logical species, and enzyme activity has described the spiro-ring-opening approach with a focus on the major mechanisms controlling their luminescence behavior h12CR1910i. The design and synthesis of other derivatives to be used as sensors of gold species h12CC11229i and other specific metal cations h12PC823i have also been described. Recent advances related to coumarin-derived fluorescent chemosen- sors for metal ions h12COC2690i and to monitoring in vitro analysis and cellular imaging of monoamine oxidase activity h12CC6833i have been discussed. The study of various organic chromophores allowed the synthesis of novel dica- tionic phloroglucinol-type bisflavylium pigments h12SL2053i, and the optical and spectroscopic properties of several synthetic 6-aryldibenzo[b,d]pyrylium salts were explored h12TL6433i. Discussion of specific reactions leading to O- and S-membered heterocyclic compounds covers intramolecular radical cyclization h12S2475i and asymmetric enamine and dienamine catalysis h12EJO865i, oxa-Michael h12CSR988i and dom- ino Knoevenagel–hetero-Diels–Alder (hDA) reactions h12T5693i, and the versatility in cycloadditions as well as nucleophilic reactions using o-quinones h12CSR1050i. The use of specific reagents relevant to this chapter includes molecular iodine h12CEJ5460, 12COS561i, samarium diiodide–water for selective reductive transfor- mations h12CC330i, o-quinone methides as versatile intermediates h12CEJ9160i, InCl3 as catalyst h12T8683i, and gold and platinum p-acid mediated insertion of alkynes into carbon–heteroatom s-bonds h12S3401i. The remainder of this chapter discusses the most studied transformations on O- and S-6-membered heterocycles

Comparative Study of Apriori Algorithm and Frequent Pattern Growth Algorithm

Frequent Pattern Matching (FPM) is a very important part of Data Mining. The main aim of Frequent Data Mining is to look for frequently occurring subsets in sequence of sets given. It is defined using various frameworks; the most commonly used being the support-based framework in which we look for items above the defined threshold value. FPM is further used in various data mining techniques as a sub problem such as classification, clustering, market analysis etc.

Petrogenesis of ultramafic rocks with abyssal peridotite affinity from the Central Bundelkhand Craton, India

The Bundelkhand craton in India preserves important records of archean geological evolution, where several ultramafic rocks belonging to the Babina Greenstone Belt (BGB) occur as isolated and oval shaped bodies. These rocks are composed of olivine, orthopyroxene, amphiboles, and serpentine along with accessory mineral phases like chromian spinel and ilmenite. Here we present the major and trace element geochemistry of these ultramafic rocks that are characterised by low SiO2 (45.16–49.00 wt%), high MgO (24.41–29.15 wt%) and moderate Fe2O3 (5.82–9.95 wt%) with high Ni (1164–1674 ppm), Cr (1532–3477 ppm) and Cu (14.7–39.5 ppm) suggesting primary magmatic nature. The rocks show low rare earth element (REE) content (ΣREE 2.1–3.5 ppm) with depleted LREE pattern and flat to slightly fractionated HREE pattern similar to abyssal peridotite signature. The Nb/Yb ratio ranges between 0.01 to 0.20 (average = 0.03), similar to that of N-MORB, suggesting magma derivation from a depleted mantle source, further substantiated by the Th/Yb vs. Ta/Yb plot. Trace elements like Ta and Pb show positive spikes, whereas La, Nb, Pr and Ce show depleted nature. The rocks generally have low platinum group elements (PGE) content (<150 ppb) except one sample where it goes up to 388 ppb. The ΣPPGE concentration is higher than ΣIPGE for all the samples and the high Pd/Ir ratio (7.55–20.98) indicating the derivation of these ultramafic rocks from low degree of partial melting. Our data suggest that the ultramafic rocks were derived from a depleted mantle source at a shallow depth with affinity towards abyssal peridotite. These rocks might represent residue after extraction of low degree melt (∼2–10%) in a mid-oceanic ridge (MOR) setting, which were captured and brought to shallow levels and subsequently exposed on the surface

Lockout and Tagout in a Manufacturing Setting from a Situation Awareness Perspective

Applying lockouts during maintenance is intended to avoid accidental energy release, whereas tagging them out keeps employees aware of what is going on with the machine. In spite of regulations, serious accidents continue to occur due to lapses during lockout and tagout (LOTO) applications. Few studies have examined LOTO effectiveness from a user perspective. This article studies LOTO processes at a manufacturing organization from a situation awareness (SA) perspective. Technicians and machine operators were interviewed, a focus group discussion was conducted, and operators were observed. Qualitative content analysis revealed perceptual, comprehension and projection challenges associated with different phases of LOTO applications. The findings can help lockout/tagout device manufacturers and organizations that apply LOTO to achieve maximum protection

Pediatric oncology services in Nepal

Cancer in children is one of the emerging noncommunicable diseases in Nepal with significant morbidity and mortality. Significant efforts are being made at the government and nongovernment level to provide awareness, early diagnosis, and effective treatment to improve the cure rate of children with cancer. The major challenges include: lack of education, late diagnosis, advanced disease at presentation, financial problems, geographical and transportation difficulties, and inconsistent supply of chemotherapy medicines