A Western-like fat diet is sufficient to induce a gradual enhancement in fat mass over generations

The prevalence of obesity has steadily increased over the last few decades. During this time, populations of industrialized countries have been exposed to diets rich in fat with a high content of linoleic acid and a low content of α-linolenic acid compared with recommended intake. To assess the contribution of dietary fatty acids, male and female mice fed a high-fat diet (35% energy as fat, linoleic acid:α-linolenic acid ratio of 28) were mated randomly and maintained after breeding on the same diet for successive generations. Offspring showed, over four generations, a gradual enhancement in fat mass due to combined hyperplasia and hypertrophy with no change in food intake. Transgenerational alterations in adipokine levels were accompanied by hyperinsulinemia. Gene expression analyses of the stromal vascular fraction of adipose tissue, over generations, revealed discrete and steady changes in certain important players, such as CSF3 and Nocturnin. Thus, under conditions of genome stability and with no change in the regimen over four generations, we show that a Western-like fat diet induces a gradual fat mass enhancement, in accordance with the increasing prevalence of obesity observed in humans.     

FlaC, a protein of Campylobacter jejuni TGH9011 (ATCC43431) secreted through the flagellar apparatus, binds epithelial cells and influences cell invasion

Type III secretion systems identified in bacterial pathogens of animals and plants transpose effectors and toxins directly into the cytosol of host cells or into the extracellular milieu. Proteins of the type III secretion apparatus are conserved among diverse and distantly related bacteria. Many type III apparatus proteins have homologues in the flagellar export apparatus, supporting the notion that type III secretion systems evolved from the flagellar export apparatus. No type III secretion apparatus genes have been found in the complete genomic sequence of Campylobacter jejuni NCTC11168. In this study, we report the characterization of a protein designated FlaC of C. jejuni TGH9011. FlaC is homologous to the N- and C-terminus of the C. jejuni flagellin proteins, FlaA and FlaB, but lacks the central portion of these proteins. flaC null mutants form a morphologically normal flagellum and are highly motile. In wild-type C. jejuni cultures, FlaC is found predominantly in the extracellular milieu as a secreted protein. Null mutants of the flagellar basal rod gene (flgF) and hook gene (flgE) do not secrete FlaC, suggesting that a functional flagellar export apparatus is required for FlaC secretion. During C. jejuni infection in vitro, secreted FlaC and purified recombinant FlaC bind to HEp-2 cells. Invasion of HEp-2 cells by flaC null mutants was reduced to a level of 14% compared with wild type, suggesting that FlaC plays an important role in cell invasion.     

Uridine phosphorylase inhibitors: chemical modification of benzyloxybenzyl-barbituric acid and its effects on urdpase inhibition.

5-(o-Benzyloxy)benzylbarbituric acid (6) and 5-(p-benzyloxy)benzylbarbituric acid (7) were prepared and their inhibitory activities compared to 5-(m-benzyloxy)-benzylbarbituric acid (BBB) a known, potent inhibitor of uridine phosphorylase (UrdPase). Compounds 6 and 7 were 18-fold and 51-fold less active, respectively, than BBB in inhibiting UrdPase. These data provide solid evidence that the 5-benzylbarbituric acids possessing meta substituents are the most active inhibitors. In addition, 2-thioBBB (11) was synthesized and it was shown to be as active an inhibitor as BBB.     

Modified Cytoplasmic Ca2+ Sequestration Contributes to Spinal Cord Injury-Induced Augmentation of Nerve-Evoked Contractions in the Rat Tail Artery

In rat tail artery (RTA), spinal cord injury (SCI) increases nerve-evoked contractions and the contribution of L-type Ca²⁺ channels to these responses. In RTAs from unoperated rats, these channels play a minor role in contractions and Bay K8644 (L-type channel agonist) mimics the effects of SCI. Here we investigated the mechanisms underlying the facilitatory actions of SCI and Bay K8644 on nerve-evoked contractions of RTAs and the hypothesis that Ca²⁺ entering via L-type Ca²⁺ channels is rapidly sequestered by the sarcoplasmic reticulum (SR) limiting its role in contraction. In situ electrochemical detection of noradrenaline was used to assess if Bay K8644 increased noradrenaline release. Perforated patch recordings were used to assess if SCI changed the Ca²⁺ current recorded in RTA myocytes. Wire myography was used to assess if SCI modified the effects of Bay K8644 and of interrupting SR Ca²⁺ uptake on nerve-evoked contractions. Bay K8644 did not change noradrenaline-induced oxidation currents. Neither the size nor gating of Ca²⁺ currents differed between myocytes from sham-operated (control) and SCI rats. Bay K8644 increased nerve-evoked contractions in RTAs from both control and SCI rats, but the magnitude of this effect was reduced by SCI. By contrast, depleting SR Ca²⁺ stores with ryanodine or cyclopiazonic acid selectively increased nerve-evoked contractions in control RTAs. Cyclopiazonic acid also selectively increased the blockade of these responses by nifedipine (L-type channel blocker) in control RTAs, whereas ryanodine increased the blockade produced by nifedipine in both groups of RTAs. These findings suggest that Ca²⁺ entering via L-type channels is normally rapidly sequestered limiting its access to the contractile mechanism. Furthermore, the findings suggest SCI reduces the role of this mechanism.     

The effects of Nigella sativa on bile duct ligation induced‐liver injury in rats

Nigella sativa (NS) has been shown to have antioxidant and antiinflammatory activities in different conditions. The goal of this study was to evaluate the effects of NS on cholestatic liver injury in rats. Thirty rats were recruited in the study as follows: Group 1, Bile duct ligation (BDL) (n = 10); Group 2, BDL plus NS (n = 10); and Group 3, Sham (n = 10). Bile duct ligated group received 0.2 mL kg^?1 dose of NS intraperitoneally daily throughout 14 days. Liver damage and cholestasis were determined by the biochemical and the pathologic examination. Data showed a decrease in gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities of the NS treated rats when compared with BDL group (p < 0.001 for GGT and p < 0.05 for others). The NS treated rats' tissue levels of total oxidant status (TOS), oxidative stress index (OSI), and myeloperoxidase (MPO) were significantly lower than that of the BDL group (p < 0.01 for all). Increases in total antioxidant capacity (TAC) and catalase (CAT) levels were statistically significant in the NS treated rats compared to BDL group (p < 0.01 for both). On the other hand, administration of NS in the rats with biliary obstruction resulted in inhibition of necro‐inflammation. These results indicate that NS exerts a therapeutic effect on cholestatic liver injury in bile duct ligated rats possibly through attenuation of enhanced neutrophil infiltration and oxidative stress in the liver tissue. Copyright © 2009 John Wiley & Sons, Ltd.     

Chemical Polymorphism of Origanum compactum Grown in All Natural Habitats in Morocco

Origanum compactum L. (Lamiaceae) is one of the most important medicinal species in term of ethnobotany in Morocco. It is considered as a very threatened species as it is heavily exploited. Its domestication remains the most efficient way to safeguard it for future generations. For this purpose, wide evaluation of the existing variability in all over the Moroccan territory is required. The essential oils of 527 individual plants belonging to 88 populations collected from the whole distribution area of the species in Morocco were analyzed by GC/MS. The dominant constituents were carvacrol (0 – 96.3%), thymol (0 – 80.7%), p‐cymene (0.2 – 58.6%), γ‐terpinene (0 – 35.2%), carvacryl methyl ether (0 – 36.2%), and α‐terpineol (0 – 25.8%). While in the Middle Atlas region and the Central Morocco mainly carvacrol type samples were found, much higher chemotypic diversity was encountered within samples from the north part of Morocco (occidental and central Rif regions). The high chemical polymorphism of plants offers a wide range for selection of valuable chemotypes, as a part of breeding and domestication programs of this threatened species.     

First Homo erectus from Turkey and implications for migrations into temperate Eurasia

Remains of fossil hominins from temperate regions of the Old World are rare across both time and space, but such specimens are necessary for understanding basic issues in human evolution including linkages between their adaptations and early migration patterns. We report here the remarkable circumstances surrounding the discovery of the first fossil hominin calvaria from Turkey. The specimen was found in the Denizli province of western Turkey and recovered from within a solid block of travertine stone as it was being sawed into tile-sized slabs for the commercial natural stone building market. The new specimen fills an important geographical and temporal gap and displays several anatomical features that are shared with other Middle Pleistocene hominins from both Africa and Asia attributed to Homo erectus. It also preserves an unusual pathology on the endocranial surface of the frontal bone that is consistent with a diagnosis of Leptomeningitis tuberculosa (TB), and this evidence represents the most ancient example of this disease known for a fossil human. TB is exacerbated in dark-skinned peoples living in northern latitudes by a vitamin D deficiency because of reduced levels of ultraviolet radiation (UVR). Evidence for TB in the new specimen supports the thesis that reduced UVR was one of the many climatic variables presenting an adaptive challenge to ancient hominins during their migration into the temperate regions of Europe and Asia.     

A rapid exocytosis mode in chromaffin cells with a neuronal phenotype

We have used astrocyte-conditioned medium (ACM) to promote the transdifferentiation of bovine chromaffin cells and study modifications in the exocytotic process when these cells acquire a neuronal phenotype. In the ACM-promoted neuronal phenotype, secretory vesicles and intracellular Ca2+ rise were preferentially distributed in the neurite terminals. Using amperometry, we observed that the exocytotic events also occurred mainly in the neurite terminals, wherein the individual exocytotic events had smaller quantal size than in undifferentiated cells. Additionally, duration of pre-spike current was significantly shorter, suggesting that ACM also modifies the fusion pore stability. After long exposure (7-9 days) to ACM, the kinetics of catecholamine release from individual vesicles was markedly accelerated. The morphometric analysis of vesicle diameters suggests that the rapid exocytotic events observed in neurites of ACM-treated cells correspond to the exocytosis of large dense-core vesicles (LDCV). On the other hand, experiments performed in EGTA-loaded cells suggest that ACM treatment promotes a better coupling between voltage-gated calcium channels (VGCC) and LDCV. Thus, our findings reveal that ACM promotes a neuronal phenotype in chromaffin cells, wherein the exocytotic kinetics is accelerated. Such rapid exocytosis mode could be caused at least in part by a better coupling between secretory vesicles and VGCC.     

Immunolocalization of androgen and vitamin D receptors in the epididymis of mature ram (Ovis aries)

This study illustrated the immunohistochemical distribution of androgen and vitamin D receptors of epididymis in 20 sexually mature ram (Rahmani breed) with average age ranged from (2^_4) years and average weight ranged from (50^_65kg). Androgen receptor was localized in the cytoplasm of both ciliated and non ciliated cells of efferent ductules, besides the principal cells via the entire epididymal duct. The principal cells of both corpus and proximal cauda epididymis showed the highest immunoreactivity to androgen receptors. Furthermore, vitamin D receptor was localized in the cytoplasm of all epithelium of the efferent ductules besides principal cells of all epididymal regions, however the immunoreaction was significantly higher in the efferent ductules, distal caput and distal cauda epididymis. In conclusion, these results suggest that the function of ram epididymis is regulated by both androgen and Vitamin D.     

Morphology and SSU rRNA gene‐based phylogeny of two Diophrys‐like ciliates from northern china,with notes on morphogenesis of Pseudodiophrys nigricans (Protozoa,Ciliophora)

Two free‐living marine euplotid ciliates, Pseudodiophrys nigricans and Diophrys japonica, collected from the coastal waters off Qingdao, northern China, were investigated using live observations and protargol impregnation methods. The cortical development of P. nigricans was observed during binary division. Although its general pattern of morphogenesis is similar to that of other Diophrys‐like species, three unusual features are noteworthy: 1) the frontoventral transverse cirral anlagen develop in the secondary mode, similar to that of Euplotes; 2) the undulating membrane anlage migrates far from the cytostome and does not split into two membranes; and 3) the parental adoral zone of membranelles remains nearly intact throughout the entire morphogenetic process. Diophrys japonica is redescribed based on a Chinese population and can be recognized by having one left marginal cirrus, densely arranged cortical granules, and a fragment kinety with three dikinetids. Phylogenetic analyses based on the small subunit rRNA (SSU rRNA) gene sequence data indicate that D. japonica is placed within the Diophrys clade and is most closely related to the well‐known D. apoligothrix. © J. Morphol., 2013. © 2012 Wiley Periodicals, Inc.