Synthesis and Biological Evaluation of Novel Apio Nucleosides with Thiazole‐4‐carboxamide and 1,2,4‐Triazole‐3‐carboxamide

In view of biological activities of azole nucleosides and apio‐dideoxynucleoside, novel apio nucleoside analogues (1 and 2) with thiazole and triazole base moiety were synthesized using 2,3‐O‐isopropylidene‐apio‐β‐d‐furanose (3), which was prepared from d‐mannose.     

Intra‐ethnic and inter‐ethnic marriage and divorce in Hawaii

Abstract

A comparison of intra‐ and inter‐ethnic divorce rates in Hawaii showed that inter‐ethnic marriages resulted in a higher proportion of divorces than did intra‐ethnic marriages when the marriage data used had to do with all marriages occurring in Hawaii. However, a sizeable portion of marriages in Hawaii are of nonresidents who, if they divorce, probably divorce elsewhere. Nonresident marriages are chiefly intra‐ethnic marriages of Caucasians. When examining the proportions of divorces to resident marriages, within‐group marriages are more at risk than inter‐ethnic marriages. As in prior research, persons who marry members of other racial/ethnic groups tend to marry persons from groups with income levels similar to their own. As in previous reports, some cross‐ethnic combinations appeared more at risk for divorce than did others. Group income appeared to be a predictor of risk. When considering only resident marriages as related to divorces, those marriages in which the bride was from a higher income group than the groom were at a significantly greater risk for divorce than marriage in which the bride came from an income group lower than that of the groom.     

Synthesis and Antiviral Properties of Arabino and Ribonucleosides of 1,3‐Dideazaadenine, 4‐Nitro‐1, 3‐dideazaadenine and Diketopiperazine

Different arabinosides and ribosides, viz. Ara‐DDA or 9(1‐β‐d‐arabinofuranosyl) 1,3‐dideazaadenine (6), Ara‐NDDP or 9(1‐β‐d‐arabinofuranosyl) 4‐nitro‐1,3‐dideazapurine (7), Ara‐DKP or 1(1‐β‐d‐arabinofuranosyl) diketopiperazine (8), Ribo‐DDA or 9(1‐β‐d‐ribofuranosyl) 1,3‐dideazaadenine (9) and Ribo‐NDDP or 9(1‐β‐d‐ribofuranosyl) 4‐nitro‐1,3‐dideazapurine (10) have been synthesized as probable antiviral agents. The arabinosides have been synthesized using the catalyst TDA‐1 that causes stereospecific formation of β‐nucleosides while a one‐pot synthesis procedure was adopted for the synthesis of the ribonucleosides where β‐anomers were obtained in higher yields. All the five nucleoside analogs have been screened for antiviral property against HIV‐1 (III_B), HSV‐1 and 2, parainfluenza‐3, reovirus‐1 and many others. It was observed that arabinosides had greater inhibitory action than ribosides. The compound 7 or Ara‐NDDP has shown maximum inhibition of HIV‐1 replication than the rest of the molecules with an IC₅₀ of 79.4 µg/mL.     

Design,Efficient Synthesis,and Anti‐HIV Activity of 4′‐C‐Cyano‐ and 4′‐C‐Ethynyl‐2′‐deoxy Purine Nucleosides

Some 4′‐C‐ethynyl‐2′‐deoxy purine nucleosides showed the most potent anti‐HIV activity among the series of 4′‐C‐substituted 2′‐deoxynucleosides whose 4′‐C‐substituents were methyl, ethyl, ethynyl and so on. Our hypothesis is that the smaller the substituent at the C‐4′ position they have, the more acceptable biological activity they show. Thus, 4′‐C‐cyano‐2′‐deoxy purine nucleosides, whose substituent is smaller than the ethynyl group, will have more potent antiviral activity. To prove our hypothesis, we planned to develop an efficient synthesis of 4′‐C‐cyano‐2′‐deoxy purine nucleosides (4′‐CNdNs) and 4′‐C‐ethynyl‐2′‐deoxy purine nucleosides (4′‐EdNs). Consequently, we succeeded in developing an efficient synthesis of six 2′‐deoxy purine nucleosides bearing either a cyano or an ethynyl group at the C‐4′ position of the sugar moiety from 2′‐deoxyadenosine and 2,6‐diaminopurine 2′‐deoxyriboside. Unfortunately, 4′‐C‐cyano derivatives showed lower activity against HIV‐1, and two 4′‐C‐ethynyl derivatives suggested high toxicity in vivo.     

Thiosugar Nucleosides. Synthesis and Biological Activity of 1,3,4‐Thiadiazole,Thiazoline and Thiourea Derivatives of 5‐Thio‐d‐Glucose

New acylated 5‐thio‐β‐d‐glucopyranosylimino‐disusbstituted 1,3,4‐thiadiazols 8, and 11 were prepared, via spontaneous rearrangements, by cycloaddition of the glycosyl isothiocyanate 2 with the reactive intermediates 1‐aza‐2‐azoniaallene hexachloroantimonates 4 and 6, respectively. Reaction of 2 with aminoacetone or chloroethylamine afforded the acylated 5‐thio‐β‐d‐glucopyranosyl‐4‐imidazoline‐2‐thione nucleoside 16 and glucopyranosylamino‐2‐thiazoline derivative 18, respectively. Deblocking of 8, 11, 17 and 19 furnished the free nucleoside analogues 9, 12, 18 and 20, respectively. Analogously, treatment of 2 with chloroethylamine in the 1:2 ratio afforded the thioureylendisaccharide 21. No in vitro antiviral activity against HIV‐1, HIV‐2, human cytomegallovirus (HMCV), has been found for the new synthesized compounds.     

Overweight and obesity among foreign‐born and U.S.‐born Hispanics

Abstract

In this study, data from the New Immigrant Survey and the National Health and Nutrition Examination Survey are combined to examine patterns of overweight and obesity among U.S.‐born and foreign‐born Hispanics. Results indicate that, after using height and weight measures adjusted for self‐reporting bias, foreign‐born Hispanic men and women have substantially lower likelihoods of being overweight and obese than the U.S.‐born. However, both likelihoods increase as years in the U.S. accumulate for the foreign‐born. Controls for smoking behavior, physical activity, and the degree of dietary change do not reduce the strength of the positive relationship between years in the U.S. and overweight/obesity.     

Messinian‐Zanclean vegetation and climate in North‐Central Italy

A palynological study was carried out on four Italian Miocene‐Pliocene sections ranging in age from uppermost Tortonian to Zanclean located on the Adriatic side of the North‐Central Apennines. The study documents the Mediterranean isolation, the salinity crisis (s.s), the “lago‐mare”; event and the re‐establishment of open‐marine conditions in the Mediterranean at the beginning of the Pliocene. From a climatic point of view, a transition from subtropical/warm‐temperate conditions during the Messinian to warm‐temperate/temperate conditions during the Zanclean is recorded. The presence of a lower thermic level, with respect to the Messinian, the re‐establishment of open‐marine conditions and the uplift of the Apennines were major factors controlling paleoenvironmental variations during the Zanclean. The latter is also characterized by cyclic temperature oscillations. Correlations with coeval sections in the Mediterranean area confirm the existence of latitudinal climatic gradients within the studied area.     

Synthesis of Oligoribonucleotides Containing 4‐Thiouridine Using the Convertible Nucleoside Approach and the 1‐(2‐Fluorophenyl)‐4‐Methoxypiperidin‐4‐yl Group

Oligoribonucleotides containing 4‐thiouridine were prepared using the Fpmp group for protection of the 2′‐OH. Two uridine derivatives with the 1,2,4‐triazolyl and the 2‐nitrophenyl groups at position 4 were used to obtain 4‐thiouridine by postsynthetic substitution with sodium hydrogen sulfide. Both uridine derivatives allow the preparation of the desired oligonucleotides in good yields.     

Are pathogenic bacteria just looking for food? Metabolism and microbial pathogenesis

It is interesting to speculate that the evolutionary drive for microbes to develop pathogenic characteristics was to access the nutrient resources that animals provided. Animal environments that pathogens colonize have likely driven the evolution of new bacterial characteristics to maximize these new nutritional opportunities. This review focuses on genomic and functional aspects of pathogen metabolism that allow efficient utilization of nutrient resources provided by animals. Similar to genes encoding specific virulence traits, genes encoding metabolic functions have been horizontally acquired by pathogens to provide a selective advantage in host tissues. Selective advantage in host tissues can also be gained by loss of function mutations that alter metabolic capabilities. Greater understanding of bacterial metabolism within host tissues should be important for increased understanding of host-pathogen interactions and the development of future therapeutic strategies.     

Plants‐associated microflora and the remediation of oil‐contaminated soil

The use of plants and their rhizospheric microorganisms is a promising emerging technology for remediating contaminated soils. The degradation of total petroleum hydrocarbon (TPH) in the rhizospheric and nonrhizospheric soil of three domestic plants, namely, alfalfa (Medicaga sativa) broad beans (Vicia faba) and ryegrass (Lolium perenne) was investigated. The experimental data from the studies of plantmicrobe‐soil interactions implicated the enhancement of TPH degradation by the rhizospheric microbial community. Although the three domestic plants exhibited normal growth in the presence of ～1.0% TPH, the degradation was more profound in the case of leguminous plants. The TPH degradation in the soil cultivated with broad beans and alfalfa was 36.6 and 35.8%, respectively, compared with 24% degradation in case of ryegrass. Such a high correlation between plant type and TPH degradation rates indicate that selection for enhanced rhizosphere degradation may be accomplished by selecting leguminous plants.     

One‐Pot Solvent Free Synthesis and DNA Binding Studies of Thieno[2,3‐b]‐1,8‐Naphthyridines

Abstract

With the aim of evaluating interaction between double‐stranded calf thymus (ds)DNA and sulphur containing fused planar rings, the derivatives of 1,8‐naphthyridine containing thiono groups were synthesized by the condensation of 2‐mercapto‐3‐formyl[1,8]naphthyridines using 1‐chloroacetone, 2‐chloroacetamide, chloroaceticacid, and 2‐chloro‐1‐phenylethanone in the presence of anhydrous potassium carbonate as s catalyst under solvent free microwave irradiation. The structures of the compounds were elucidated on the basis of elemental analysis, IR, ¹H NMR, and mass spectra. The interaction of thieno[2,3‐b]‐1,8‐naphthyridine‐2‐carboxylic acid (TNC) (3a) with ct‐DNA was studied by UV‐Vis spectrophotometry, viscosity, thermal denaturation, as well as cyclic voltammetry experiments. On binding to DNA, the absorption spectrum underwent bathochromic and hypochromic shifts. Binding parameters, determined from spectrophotometric measurements indicated a binding constant of K _b =2.1×10⁶ M^?1. The thieno[2,3‐b]‐1,8‐naphthyridine‐2‐carboxylic acid (3a) increases the viscosity of sonicated rod‐like DNA fragments. The binding of TNC to DNA increased the melting temperature by about 4°C. The decrease in peak current heights and shifts of peak potential values are observed by the addition of calf thymus DNA in cyclic voltammetry studies.     

Improved and Reliable Synthesis of 3′‐Azido‐2′,3′‐dideoxyguanosine Derivatives

An improved synthesis of N²‐protected‐3′‐azido‐2′,3′‐dideoxyguanosine 20 and 23 is described. Deoxygenation of 2′‐O‐alkyl (and/or aryl) sulfonyl‐5′‐dimethoxytritylguanosine coupled with [1,2]‐hydride shift rearrangement gave protected 9‐(2‐deoxy‐threo‐pentofuranosyl)guanines ( 10 , 12 and 16 ). This rearrangement was accomplished in high yield with a high degree of stereoselectivity using lithium triisobutylborohydride (l‐Selectride®). Compounds 10 , 12 and 16 were transformed into 3′‐O‐mesylates ( 18 and 21 ), which can be used for 3′‐substitution. The 3′‐azido nucleosides were obtained by treatment of 18 and 21 with lithium azide. This procedure is reproducible with a good overall yield.     

Microbrachiopods and the end‐Ordovician event

Millimetre sized chitinophosphatic brachiopods ("microbrachiopods") largely, but by no means entirely, centred around the family Acrotretidae are commonly regarded as being in decline after the early Ordovician. Work on Irish Upper Ordovician limestones however shows that this is not the case, material recovered showing both numerical abundance and taxonomic diversity in beds of Ashgill age. Although forms are known from the Devonian, the published record of these neglected fossils from the Silurian is sparse, so that the effects, if any, of the end‐Ordovician event on this ecologically enigmatic group cannot as yet be determined.     

Circadian Variations in the Activities of 6‐Phosphogluconate Dehydrogenase and Glucose‐6‐Phosphate Dehydrogenase in the Liver of Conrol and Streptozotocin‐Induced Diabetic Rats

The aim of this study was to examine: the 24 h variation of 6‐phosphogluconate dehydrogenase and glucose‐6‐phosphate dehydrogenase activities, key enzymes for the maintenance of intracellular NADPH concentration, in rat liver in control and streptozotocin‐induced diabetic animals. Adult male rats were fed ad libitum and synchronized on a 12:12 h light‐dark cycle (lights on 08:00 h). One group of animals was treated with streptozotocin (STZ, 55 mg/kg, intraperitoneal) to induce experimental diabetes. Eight weeks after STZ injection, the animals were sacrificed at six different times of day—1, 5, 9, 13, 17 and 21 Hours After Lights On (HALO)—and livers were obtained. Enzyme activities were determined spectrophotometrically in triplicate in liver homogenates and expressed as units per mg protein. 6‐phosphogluconate dehydrogenase activity was measured by substituting 6‐phosphogluconate as substrate. Glucose‐6‐phosphate dehydrogenase activity was determined by monitoring NADPH production. Treatment, circadian time, and interaction between treatment and circadian time factors were tested by either one or two way analysis of variance (ANOVA). Two‐way ANOVA revealed that 6‐phosphogluconate dehydrogenase activity significantly depended on both the treatment and time of sacrifice. 6‐phosphogluconate dehydrogenase activity was higher in control than diabetic animals; whereas, glucose‐6‐phosphate dehydrogenase activity did not vary over the 24 h in animals made diabetic by STZ treatment. Circadian variation in the activity of 6‐phosphogluconate dehydrogenase was also detected in both the control and STZ treatment groups (one‐way ANOVA). Time‐dependent variation in glucose‐6‐phosphate dehydrogenase activity during the 24 h was detected in control but not in diabetic rats. No significant interaction was detected between STZ‐treatment and time of sacrifice for both hepatic enzyme activities. These results suggest that the activities of NADPH‐generating enzymes exhibit 24 h variation, which is not influenced by diabetes.     

An Efficient Route to Novel 4,5‐Di‐ and 2,4,5‐Tri Substituted Imidazoles from Imidazo[1,5‐a]‐1,3,5‐triazine (5,8‐Diaza‐7,9‐dideazapurine) Derivatives

Two new types of imidazole derivatives: N‐(2‐R¹‐5‐R²‐1H‐imidazol‐4‐yl) thioureas 7a–g and N‐(2‐R¹‐5‐R²‐1H‐imidazol‐4‐yl) formamides 8b,c,g were obtained in high yields by the hydrolytic degradation of 6‐R¹‐8‐R²‐2‐thioxo‐2,3‐dihydroimidazo[1,5‐a]‐1,3,5‐triazin‐4(1H)‐ones 5a–g and 6‐R¹‐8‐R²‐imidazo[1,5‐a]‐1,3,5‐triazin‐4(3H)‐ones 6b,c,d, respectively. The tautomeric preferences of the new imidazoles were determined.     

The uptake and metabolism of fructose‐1,6‐diphosphate in rat cardiomyocytes

Fructose1,6diphosphate (FDP) is a glycolytic intermediate which has been theorized to increase the metabolic activity of ischemic tissues. Here we examine the effects of externally applied FDP on cardiomyocyte uptake and metabolism. Adult rat cardiomyocytes were isolated and exposed to varying concentrations (0, 5, 25 and 50 mM) of FDP for either 1, 16 or 24 h of hypoxia (95% N₂/5% CO₂), each time period followed by a 1 h reoxygenation (95% air/5% CO₂). The uptake of FDP by rat cardiomyocytes was more concentrationdependent than timedependent. Furthermore, the uptake of FDP by the cardiomyocytes was similar in the hypoxia and normoxia treated cells. Alamar Blue, a redox indicator that is sensitive to metabolic activity, was used to monitor the effects of the FDP on cardiomyocyte metabolism. In the 1 h hypoxia or normoxia group, the 5, 10 and 25 mM FDP showed a significant increase in metabolism compared to the control cells. When the length of hypoxia was extended to 16 h, all doses of FDP were greater than control. And at the 24 h hypoxia or normoxia time period, only the 10, 25 and 50 mM FDP groups were greater than control. The results indicate a non-linear trend between the external concentration of FDP and the changes noted in metabolism. The findings from this study indicate that a narrow concentration range between 5–10 mM augments cardiomyocyte metabolism, but higher or lower doses may have little additional affect.     

Non‐pathogenic association of L‐form bacteria (pseudomonas syringae pv. phaseolicola) with bean plants (Phaseolus vulgaris L.) and its potential for biocontrol of halo blight disease

L‐forms of the halo blight pathogen, Pseudomonas syringae phaseolicola, were maintained in a medium which suppressed cell wall synthesis. These L‐forms, unlike revertants (walled forms derived from unstable L‐forms) and cell walled (parent) organisms, did not elicit a hypersensitive response in tobacco leaves. Association of L‐forms with Phaseolus vulgaris was established by seed imbibition in L‐form suspensions compared with appropriate control treatments (5% mannitol or heat‐killed cells). Seedling emergence and plant growth was not affected by L‐form imbibition. The association was detected by agglutination assays using polyclonal antibody. The L‐form association was localized to the lower shoot tissue and was progressively lost with age of plants. Plants with associated L‐forms had vigour and shoot weights equivalent to controls and showed no disease symptoms. The cell walled form could not be isolated from plants showing positive agglutination. On challenge with the pathogen, plants associated with L‐forms showed significantly less disease symptoms than controls. Stem extracts, from associated plants, were inhibitory to in vitro cultures of both L‐forms and parent forms of Ps. syr. phaseolicola. These results indicate that L‐form associations confer induced systemic resistance to bean plants and might be developed as novel biocontrol systems.     

Chitooligosaccharide sensing and downstream signaling: contrasted outcomes in pathogenic and beneficial plant–microbe interactions

In plants, short chitin oligosaccharides and chitosan fragments (collectively referred to as chitooligosaccharides) are well-known elicitors that trigger defense gene expression, synthesis of antimicrobial compounds, and cell wall strengthening. Recent findings have shed new light on chitin-sensing mechanisms and downstream activation of intracellular signaling networks that mediate plant defense responses. Interestingly, chitin receptors possess several lysin motif domains that are also found in several legume Nod factor receptors. Nod factors are chitin-related molecules produced by nitrogen-fixing rhizobia to induce root nodulation. The fact that chitin and Nod factor receptors share structural similarity suggests an evolutionary conserved relationship between mechanisms enabling recognition of both deleterious and beneficial microorganisms. Here, we will present an update on molecular events involved in chitooligosaccharide sensing and downstream signaling pathways in plants and will discuss how structurally related signals may lead to such contrasted outcomes during plant–microbe interactions.     

Building cross‐cultural coalitions: A case‐study of the Black‐Korean Alliance and the Latino‐Black Roundtable

A case‐study is presented of two Los Angeles‐based cross‐cultural coalitions, the Black‐Korean Alliance [BKA] and the Latino‐Black Roundtable [LBR]. An analysis of the development and eventual dissolution of these two coalitions is presented against the backdrop of the history of relations between the African‐American, Korean‐American and Latino communities of Los Angeles. The central issues leading to the breakup of the two coalitions were: lack of resources, internal power dynamics between coalition partners, nationalistic factions within the broader communities, cross‐cultural dynamics between coalition members, the use of a dialogue model to frame coalition activities, and the analysis of intergroup relations underlying the formation of the coalitions. The applied and theoretical implications of the research are discussed.