A chemical-modification approach to the olfactory code. Studies with a thiol-specific reagent

The effects of thiol-specific reagents on the amplitude of the electro-olfactogram (E.O.G.) responses elicited from frog olfactory mucosa by pulses of odorant vapours was studied. The impermeant thiol-specific reagent mersalyl [(3-{[2-(carboxymethoxy)-benzoyl]amino}-2-methoxypropyl)hydroxymercury monosodium salt] brings about a rapid decrease in the E.O.G. signal obtained with the odorant pentyl acetate. The extent of the decrease is proportional to the concentration of the mersalyl applied and the effect of the reagent is partially but incompletely reversed by treatment of the labelled mucosa with dithiothreitol. The sites labelled by mersalyl can be protected by pretreating the mucosa with a dilute solution of the odorant pentyl acetate and leaving the solution in contact with the tissue after the addition of mersalyl. When the protecting odorant is washed out of the tissue, the original E.O.G. amplitude is regained. Pentyl acetate applied to the mucosa protected the E.O.G. response to vapour pulses of the following odorants from the effects of mersalyl: n-butyric acid, n-butyl acetate, phenylacetaldehyde and cineole (1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane). The pentyl acetate applied to the mucosa failed to protect the E.O.G. response to vapour pulses of the following odorants from the effects of mersalyl: butan-1-ol, benzyl acetate, nitrobenzene, beta-ionone and linalyl acetate. The significance of the differential protection effects for the odour-quality-coding mechanism in the olfactory primary neurons is discussed. It is suggested that the olfactory code at this level of the olfactory system may be elucidated by chemical-modification methods.     

Heat‐shock proteins and cross‐tolerance in plants

Environmental stresses dramatically affect plant survival and productivity. Because plants are immobile, presumably different strategies are required for protection against transient stresses. Under stress, plants synthesize specific proteins, and their accumulation has a role in protecting the tissue from possible damage. An increasing number of studies show the existence of cross‐tolerance in plants: Exposure of tissue to moderate stress conditions often induces resistance to other stresses. Many varied mechanisms explaining the phenomenon of cross‐tolerance have been proposed, and they often, but not always, suggest that specific proteins are induced by one kind of stress and are involved in the protection against other kinds. Although various cross‐protections have been demonstrated in a number of plants, a common mechanism has not been found. This review discusses heat‐shock proteins and their possible roles in protecting the plant under heat and other stresses.     

Organotypic culture of human ovarian surface epithelial cells: A potential model for ovarian carcinogenesis

Summary The objective of this work was to establish an in vitro multidimensional culture system for human ovarian surface epithelial (HOSE) cells as a model for ovarian carcinogenesis. The epithelial origin of cell outgrowth from cells obtained from the ovarian surface was confirmed by keratin staining. Two cultures from two different patients were established, HOSE-A and HOSE-B. Cultures were infected with a retrovirus expressing human papillomavirus genes E6 and E7 to extend their life span. HOSE cells were seeded onto collagen gels containing NIH3T3-J2 fibroblasts as feeder cells and grown to confluence submerged in growth medium. The collagen bed was then raised to the air-medium interface for 7 d (organotypic culture). Microscopically, fixed cultures revealed a single layer of flat cells growing on the collagen surface, reminiscent of HOSE cells in vivo. Infected HOSE-A and HOSE-B cells exhibited aberrant growth because they stratified. In addition, established ovarian cancer lines grown in this fashion stratified and showed malignant phenotypes. Thus, cells grown in organotypic culture resemble their in vivo counterparts, providing a basis for establishing a system to study growth, proliferation, differential gene expression, and perhaps malignant transformation of HOSE cells.     

Synthesis and Computational Exploration of Morpholine Bearing Halogenated Sulfonamides as Potential Tyrosinase Inhibitors

In the presented work, a new series of three different 4-((3,5-dichloro-2-[(2/4-halobenzyl)oxy]phenyl)sulfonyl)morpholines was synthesized and the structure of these compounds were corroborated by ¹H-NMR & ¹³C-NMR studies. The in vitro results established all the three compounds as potent tyrosinase inhibitors relative to the standard. The Kinetics mechanism plots established that compound 8 inhibited the enzyme non-competitively. The inhibition constants K_i calculated from Dixon plots for this compound was 0.0025 μM. Additionally, computational techniques were used to explore electronic structures of synthesized compounds. Fully optimized geometries were further docked with tyrosinase enzyme for inhibition studies. Reasonably good binding/interaction energies and intermolecular interactions were obtained. Finally, drug likeness was also predicted using the rule of five (RO5) and Chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics. It is anticipated that current experimental and computational investigations will evoke the scientific interest of the research community for the above-entitled compounds.     

Synthesis of Nh-acyl-α-aminoamides on rink resin: Inhibitors of the hematopoietic protein tyrosine phosphatase (HePTP)

Cinnamic acid derivatives were prepared on Rink resin using tert-butyl-4-carboxycinnamate in a four-component Ugi condensation. Inhibition of the hematopoietic protein tyrosine phosphatase (HePTP) by these small molecules is reported. An IC₅₀ value of 3.9 μM was determined for the most potent inhibitor discovered.     

Flavonoids and terpenoids from Helichrysum forskahlii

Three new flavonoids, namely helichrysone A (1), helichrysone B (2) and helichrysone C (3) were isolated from the aerial parts of Helichrysum forskahlii, together with 10 known flavonoids, three triterpenes, and one sesquiterpene. The structures of the new flavonoids 1-3 were established by 1D and 2D NMR spectral data. In addition, the antimicrobial activities of the isolated compounds were determined.     

Trace Element Levels in Hashimoto Thyroiditis Patients with Subclinical Hypothyroidism

The present study was conducted to evaluate the serum copper, zinc, magnesium, and selenium levels in patients with subclinical hypothyroidism in the iodine-rich region of Ankara, Turkey. The effects of hormone replacement therapy on these elements were also studied in these patients. Basal levels of selenium and iron in patients were significantly lower than control group (67.7 +/- 10.4 vs. 83.7 +/- 17.3 microg/dl, p = 0.02; 55.7 +/- 38 vs 275.7 +/- 24, P = 0.03 microg/dl). Serum magnesium levels were significantly higher in patient group (2.16 +/- 0.31 vs 1.95 +/- 0.13 mg/dl, P < 0.0001). There was a correlation between selenium levels with hsCRP (r = -0.408, p = 0.007). HsCRP levels in patients with selenium levels <80 microg/l (n = 31) was significantly higher than hsCRP levels in patients with selenium levels >80 microg/l (n = 12; 1.99 +/- 1.0; 1.02 +/- 0.9, p = 0.014). None of these biochemical risk factors and trace elements have changed after euthyroidism in patients with SH when compared to pretreatment levels. Selenium deficiency may contribute to cardiovascular disease risk in these patients.     

Long- and short-range signals control the dynamic expression of an animal hemisphere-specific gene in Xenopus

Little is known of the control of gene expression in the animal hemisphere of the Xenopus embryo. Here we show that expression of FoxI1e, a gene essential for normal ectoderm formation, is expressed regionally within the animal hemisphere, in a highly dynamic fashion. In situ hybridization shows that FoxI1e is expressed in a wave-like fashion that is initiated on the dorsal side of the animal hemisphere, extends across to the ventral side by the mid-gastrula stage, and is then turned off in the dorsal ectoderm, the neural plate, at the neurula stage. It is confined to the inner layers of cells in the animal cap, and is expressed in a mosaic fashion throughout. We show that this dynamic pattern of expression is controlled by both short- and long-range signals. Notch signaling controls both the mosaic, and dorsal/ventral changes in expression, and is controlled, in turn, by Vg1 signaling from the vegetal mass. FoxI1e expression is also regulated by nodal signaling downstream of VegT. Canonical Wnt signaling contributes only to late changes in the FoxI1e expression pattern.These results provide new insights into the roles of vegetally localized mRNAs in controlling zygotic genes expressed in the animal hemisphere by long-range signaling. They also provide novel insights into the role of Notch signaling at the earliest stages of vertebrate development.