Synthesis and bioevaluation of N-(arylalkyl)-homospermidine conjugates

N1-(Arylalkyl)homospermidines (1c-1f) and terminally piperazine-substituted homospermidine conjugates (2a-2e) were synthesized and evaluated for cytotoxicity in mouse leukemia L1210, alpha-difluoromethylornithine (DFMO)-treated L1210, melanoma B16, spermidine (SPD)-treated B16, and HeLa cell lines. Results demonstrated that homospermidine was a more effective vector than piperazine-substituted homospermidine in ferrying diverse arenes into cells via the polyamine transporter. The leading compound, 9-anthracenemethyl-homospermidine (1a), was shown to induce apoptosis in B16 cells and IL-3 dependent FL5.12A pro-B cells. The novel conjugate 4-biphenylmethyl-homospermidine (1e) could also induce apoptosis. However, it exhibited different effect on the cell cycle of B16 cells compared to 1a.     

Carbonic anhydrase inhibitors. Inhibition of isoforms I, II, IV, VA, VII, IX, and XIV with sulfonamides incorporating fructopyranose-thioureido tails

A series of aromatic/heterocyclic sulfonamides incorporating 2,3:4,5-bis-O-(isopropylidene)-beta-d-fructopyranosyl-thioureido moieties has been synthesized and assayed for the inhibition of seven human isoforms of the zinc enzyme carbonic anhydrase (hCA, EC 4.2.1.1). The new derivatives behaved as weak hCA I inhibitors (K(I)s of 9.4 -13.3microM), were efficient hCA II inhibitors (K(I)s of 6-750nM), and slightly inhibited isoforms hCA IV and hCA VA. Only the sulfanilamide derivative showed efficient and selective inhibition of hCA IV (K(I) of 10nM). These derivatives also showed excellent hCA VII inhibitory activity (K(I)s of 10-79nM), being less efficient as inhibitors of the transmembrane isoforms hCA IX (K(I)s of 10-4500nM) and hCA XIV (K(I)s of 21-3500nM). Two of the new compounds showed anticonvulsant action in a maximal electroshock seizure test in mice, with the fluorosulfanilamide derivative being a more efficient anticonvulsant than the antiepileptic drug topiramate.     

Interlinking interleukin-7

The signaling processes that maintain the homeostatic proliferation of peripheral T-cells and result in their self-renewal largely remain to be elucidated. Much focus has been placed on the anti-apoptotic function of the cytokine, interleukin-7 (IL-7), during T-cell development. But a more critical role has been ascribed to IL-7 as a mediator of peripheral T-cell maintenance. The biological effects responsive to IL-7 signaling are transduced through only a few well-known pathways. In this review we will focus on the signals transduced by IL-7 and similar cytokines, examining how proliferative signals originate from cytokine receptors, are amplified and eventually alter gene expression. In this regard we will highlight the crosstalk between pathways that promote survival, drive cell cycle progression and most importantly provide the needed energy to sustain these critical cellular activities. Though this review showcases much of what has been learned about IL-7 proliferative signaling, it also reveals the significant gaps in our knowledge about cytokine signaling in the very relevant context of peripheral T-cell homeostasis.     

Redescription of a poorly known marine ciliate, Leptoamphisiella vermis Gruber, 1888 n. g., n. comb. (ciliophora, stichotrichia, pseudoamphisiellidae), from the Yellow Sea, China

Leptoamphisiella vermisGruber, 1888 n. g., n. comb. (basionym Epiclintes vermisGruber, 1888) is an extraordinarily large and worm-like marine stichotrichous ciliate. Based on a population isolated recently from coastal waters of Qingdao, China, the living morphology and infraciliature are redescribed and its taxonomic position is defined. Accordingly, a new diagnosis for this species is suggested: large, marine Leptoamphisiella with a conspicuous layer of pellicular alveoli; 400-1000 microm x 40-70 microm in vivo; body band-like, highly flexible; about 40 membranelles; always three frontal and two buccal cirri; 52-80 transverse cirri (TC) extending to the posterior end of the buccal field; 57-79 left midventral and 44-62 right midventral cirri; 62-102 cirri in left and 63-91 cirri in right marginal rows (MR); 9-13 dorsal kineties that extend the full body length; about 100 macronuclear nodules and 5-13 micronuclei. The diagnosis for the new genus is as follows: vermiform Pseudoamphisiellidae with strongly contractile body, differentiated frontal, buccal, and highly developed TC; two remarkably separated midventral rows; one MR on each side of the body; frontoterminal and caudal cirri absent. Leptoamphisiella vermis n. comb. is fixed as the type species of the new genus.     

Oxidative stress implication in a new ex-vivo cardiac concordant xenotransplantation model

Xenotransplantation (XT) reveals a growing interest for the treatment of cardiomyopathy. The major barrier is an acute vascular rejection due to an acute humoral rejection. This pathogenesis is a difficult issue and in order to elaborate means for its prevention, we analysed the implication of oxidative stress (OS) on hearts from mini-pigs followed by reperfusion with either autologous or human blood in an attempt to simulate xenotransplantation. About 14 hearts were studied after a Langendorff blood reperfusion: allografts with autologous blood (n = 7) or xenografts with human blood (n = 7). Blood samples were drawn from the coronary sinus to assess ischemia and OS. In xenografts, arrhythmias occurred more frequently (p < 0.01, left ventricular systolic pressure decreased more significantly (p < 0.05), thiobarbituric acid-reactive substances concentrations increased at 30 min (0.7 +/- 0.1 vs. 2.4 +/- 0.3 mmol/l; p < 0.05) while vitamin A levels decreased (p < 0.05). XT was associated with a significant increase in ischemic injury and OS production. OS might play an eminent role in hyperacute humoral rejection.     

Verbal cues modulate hedonic perception of odors in 5-year-old children as well as in adults

The judgment of pleasantness/unpleasantness is the prominent reaction to the olfactory world. In human adults, the hedonic valence of odor perception is affected by various factors, among which is an individual's lexical knowledge about smells. The present study examined whether such top-down effects of lexical knowledge on hedonic judgment of olfactory input are similar in children (5-6 years) and adults (20-25 years). In both groups, the lexical knowledge was found to influence the perception of the least emotional (or most neutral) odors: the pleasantness of the smells of banana and mint was enhanced when participants were given the corresponding odor label before olfactory sensation. These results lend support to the notion that, during childhood, smells are not only encoded perceptually but that verbal encoding also steers contextual effects that may be prominent factors in the early memorization and categorization of odors.     

Analysis of acetylation stoichiometry suggests that SIRT3 repairs nonenzymatic acetylation lesions

Acetylation is frequently detected on mitochondrial enzymes, and the sirtuin deacetylase SIRT3 is thought to regulate metabolism by deacetylating mitochondrial proteins. However, the stoichiometry of acetylation has not been studied and is important for understanding whether SIRT3 regulates or suppresses acetylation. Using quantitative mass spectrometry, we measured acetylation stoichiometry in mouse liver tissue and found that SIRT3 suppressed acetylation to a very low stoichiometry at its target sites. By examining acetylation changes in the liver, heart, brain, and brown adipose tissue of fasted mice, we found that SIRT3‐targeted sites were mostly unaffected by fasting, a dietary manipulation that is thought to regulate metabolism through SIRT3‐dependent deacetylation. Globally increased mitochondrial acetylation in fasted liver tissue, higher stoichiometry at mitochondrial acetylation sites, and greater sensitivity of SIRT3‐targeted sites to chemical acetylation in vitro and fasting‐induced acetylation in vivo, suggest a nonenzymatic mechanism of acetylation. Our data indicate that most mitochondrial acetylation occurs as a low‐level nonenzymatic protein lesion and that SIRT3 functions as a protein repair factor that removes acetylation lesions from lysine residues.     

Chemical composition and antibacterial activities of seven Eucalyptus species essential oils leaves

Background

In this paper, we have studied the essential oils chemical composition of the leaves of seven Eucalyptus species developed in Tunisia. Eucalyptus leaves were picked from trees growing in different arboretums in Tunisia. Choucha and Mrifeg arboretums located in Sedjnene, region of Bizerte (Choucha: E. maideni, E. astrengens et E. cinerea; Mrifeg : E. leucoxylon), Korbous arboretums located in the region of Nabeul, North East Tunisia with sub-humid bioclimate, (E. lehmani), Souiniet-Ain Drahem arboretum located in region of Jendouba (E. sideroxylon, E. bicostata). Essential oils were individually tested against a large panel of microorganisms including Staphylococcus aureus (ATCC 6539), Escherichia coli (ATCC 25922), Enterococcus faecalis (ATCC29212), Listeria ivanovii (RBL 30), Bacillus cereus (ATCC11778).

Results

The yield of essential oils ranged from 1.2% to 3% (w/w) for the different Eucalyptus species. All essential oils contain α-pinene, 1,8-cineol and pinocarveol-trans for all Eucalyptus species studied. The 1,8-cineol was the major compound in all species (49.07 to 83.59%). Diameter of inhibition zone of essential oils of Eucalyptus species varied from 10 to 29 mm. The largest zone of inhibition was obtained for Bacillus cereus (E. astrengens) and the lowest for Staphylococcus aureus (E. cinerea). The essential oils from E. maideni, E. astrengens, E. cinerea (arboretum of Bizerte), E. bicostata (arboretum of Aindraham) showed the highest antibacterial activity against Listeria ivanovii and Bacillus cereus.

Conclusion

The major constituents of Eucalyptus leaves essential oils are 1,8-cineol (49.07 to 83.59%) and α-pinene (1.27 to 26.35%). The essential oils from E. maideni, E. astrengens, E. cinerea, E. bicostata showed the highest antibacterial activity against Listeria ivanovii and Bacillus cereus, they may have potential applications in food and pharmaceutical products.     

Potential Zoonotic Trematodes Recovered in Stray Cats from Kuwait Municipality,Kuwait

Stray cats are a common feature roaming the streets and alleys of Kuwait; they could be a source of parasites, including trematodes, that affect humans. A survey was conducted to identify feline trematodes and throw the light on their public health significance in Kuwait. Out of 240 stray cats trapped from different localities of Kuwait from June 2011 to May 2012, 59 (24.6%) were found to be infected with 14 species of trematodes. The most common were trematodes of the genus Heterophyes, particularly H. heterophyes and H. dispar that were found in respectively 15.8% and 10.8% of the cats examined. Other trematodes recorded, with lower prevalences, were Heterophyes nocens (2.9%), Haplorchis taichui (3.8%), Stictodora sawakinensis (2.1%), Stellantchasmus falcatus (1.6%), Echinochasmus japonicus (1.6%), and Mesostephanus dottrensi (1.3%). Centrocestus cuspidatus, Galactosomum fregatae, Ascocotyle sp., Mesostephanus appendiculatus, Haplorchis yokogawai, and Pygidiopsis genata showed the lowest prevalence (0.4%) and intensity. The majority of the trematodes are recorded for the first time in Kuwait and even in the Gulf region. The study reveals that stray cats are good indicators of fish-borne trematodes in the environment. As all trematodes recovered are zoonotic, their significance to public health should be considred.     

Reproductive biology of the Suez Canal spider crab Schizophrys aspera (H. Milne Edwards, 1834: Crustacea: Brachyura: Majidae)

A reproductive biology study of the spider crab Schizophrys aspera (H. Milne Edwards, 1834) was conducted in the Suez Canal from July 2012 to June 2013. The annual sex ratio (Male:Female) of S. aspera was female biased with values of 1:1.25. Out of the four ovarian development stages of this crab, two stages were observed in the Suez Canal throughout the whole year. The ovigerous crab’s carapace width varied from 28 to 52 mm. This crab species can spawn during most of the year in the canal water, with a peak during late spring and early winter. The fecundity of ovigerous females ranged between 2349 and 13600 eggs with a mean of 5494 ± 1486 eggs. Female crabs that reached sexual maturity exhibited a minimum carapace width varying between 22 and 46 mm, and fifty percentage of all ovigerous females showed a carapace width of 36 mm.