Neuroadaptations in the Striatal Proteome of the Rat Following Prolonged Excessive Sucrose Intake

Obesity is a contemporary health problem of rapidly increasing prevalence. One possible cause of obesity is loss of control over consumption of highly palatable foodstuffs, perhaps mirroring the processes involved in drug addiction. Accordingly, the striatum may be a key neural substrate involved in both food and drug craving. We hypothesised here that prolonged exposure to 10 % sucrose solution might cause neuroadaptations in the striatum that are analogous to those previously reported following prolonged exposure to alcohol or recreational drugs. Male Wistar rats were given constant access to 10 % sucrose solution (in addition to normal lab chow and tap water) for 8 months and were compared with control rats receiving no sucrose access. Rats in the sucrose group typically drank more than 100 ml of sucrose solution per day and showed 13 % greater body weight than controls at the end of the 8 months. Striatal dopamine (DA) concentrations were decreased in the sucrose group rats relative to controls. Differential expression of 18 proteins was identified in the striatum of the sucrose group rats relative to controls. Down regulated proteins included pyridoxal phosphate phosphatase, involved in DA synthesis, and glutathione transferase, involved in free radical scavenging. Up regulated proteins included prolactin (which is under negative regulation by DA) and adipose differentiation-related protein, involved in fat synthesis. We hypothesise that DA-related neuroadaptations in the striatum caused by prolonged sucrose intake may partly drive compulsive intake and seeking of high palatability foodstuffs, in a similar way to that observed with drug and alcohol addictions.     

Identification of two forms of an endogenous murine retroviral env gene linked to the Rmcf locus.

The Rmcf gene restricts the replication of recombinant murine mink cell focus-inducing (MCF) viruses in cell cultures derived from mice carrying the resistance allele (Rmcfr) and may play a role in resistance to retrovirus-induced leukemias in vivo. We have characterized the endogenous gp70 expressed by Rmcfr and Rmcfs mice with a panel of type-specific monoclonal antibodies which discriminate xenotropic and MCF gp70. Embryo and tail skin cultures derived from Rmcfr mice (DBA/2 and CBA/N) expressed gp70 bearing a determinant unique to MCF viruses, whereas cultures from Rmcfs mice expressed either no detectable gp70 (NFS/N and IRW) or a gp70 serologically related to a subgroup of xenotropic viruses (C57BL/6, CBA/J, and A/WySn). Studies of progeny embryos derived from a (C57BL/6 X DBA/2) X C57BL/6 backcross established that the Rmcf resistance allele was linked to the expression of the MCF gp70 and that the gene encoding the xenotropic gp70 expressed by C57BL/6 Rmcfs mice was allelic with the MCF gp70 from Rmcfr mice. These data indicate that the Rmcf locus contains an endogenous gp70 gene having two allelic forms, one of which inhibits exogenous MCF infection in vitro by a mechanism of viral interference.     

Synthesis and fungicidal activity of novel pyrazole derivatives containing 5-Phenyl-2-Furan

Pyrazole constitutes an important heterocyclic family covering a broad range of synthetic as well as natural products that exhibit numerous chemical, biological, agrochemical and pharmacological properties. In order to explore compounds with good fungicidal activity, a series of new pyrazole derivatives containing 5-phenyl-2-furan were designed and synthesized. In vitro and in vivo fungicidal activities were evaluated and the compound ethyl-1-(5-phenylfuran-2-carbonyl)-5-propyl-1H-pyrazole-3-carboxylate (I8) displayed significant fungicidal activity against various fungi, especially against P. infestans. The structures of the novel pyrazole derivatives were confirmed by ¹H NMR, ¹³C NMR, MS, elemental analysis and X-ray single crystal diffraction. Further study showed that compound I8 might act on the synthesis of cell walls from morphological and ultrastructural studies by SEM and TEM. The results also revealed that compound I8 could block the nutritional transportation leading to cells senescence and death. These results suggested that the novel pyrazole derivatives proved to be promising lead compounds.     

Countrywide Survey for MERS-Coronavirus Antibodies in Dromedaries and Humans in Pakistan

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a zoonotic pathogen capable of causing severe respiratory disease in humans. Although dromedary camels are considered as a major reservoir host, the MERS-CoV infection dynamics in camels are not fully understood. Through surveillance in Pakistan, nasal (n = 776) and serum (n = 1050)samples were collected from camels between November 2015 and February 2018. Samples were collected from animal markets, free-roaming herds and abattoirs. An in-house ELISA was developed to detect IgG against MERS-CoV. A total of 794 camels were found seropositive for MERS-CoV. Prevalence increased with the age and the highest seroprevalence was recorded in camels aged [ 10 years (81.37%) followed by those aged 3.1–10 years (78.65%) and B 3 years (58.19%).Higher prevalence was observed in female (78.13%) as compared to male (70.70%). Of the camel nasal swabs, 22 were found to be positive by RT-qPCR though with high Ct values. Moreover, 2,409 human serum samples were also collected from four provinces of Pakistan during 2016–2017. Among the sampled population, 840 humans were camel herders.Although we found a high rate of MERS-CoV antibody positive dromedaries (75.62%) in Pakistan, no neutralizing antibodies were detected in humans with and without contact to camels.     

Erratum to: Rostrocaudal Dynamics of CSF Biomarkers

Neurochemical Research -     

Diversification of the Structural Determinants of Fibroblast Growth Factor-Heparin Interactions: IMPLICATIONS FOR BINDING SPECIFICITY*

The functions of a large number (>435) of extracellular regulatory proteins are controlled by their interactions with heparan sulfate (HS). In the case of fibroblast growth factors (FGFs), HS binding determines their transport between cells and is required for the assembly of high affinity signaling complexes with their cognate FGF receptor. However, the specificity of the interaction of FGFs with HS is still debated. Here, we use a panel of FGFs (FGF-1, FGF-2, FGF-7, FGF-9, FGF-18, and FGF-21) spanning five FGF subfamilies to probe their specificities for HS at different levels as follows: binding parameters, identification of heparin-binding sites (HBSs) in the FGFs, changes in their secondary structure caused by heparin binding and structures in the sugar required for binding. For interaction with heparin, the FGFs exhibit K_D values varying between 38 nm (FGF-18) and 620 nm (FGF-9) and association rate constants spanning over 20-fold (FGF-1, 2,900,000 m⁻¹ s⁻¹ and FGF-9, 130,000 m⁻¹ s⁻¹). The canonical HBS in FGF-1, FGF-2, FGF-7, FGF-9, and FGF-18 differs in its size, and these FGFs have a different complement of secondary HBS, ranging from none (FGF-9) to two (FGF-1). Differential scanning fluorimetry identified clear preferences in these FGFs for distinct structural features in the polysaccharide. These data suggest that the differences in heparin-binding sites in both the protein and the sugar are greatest between subfamilies and may be more restricted within a FGF subfamily in accord with the known conservation of function within FGF subfamilies.     

Stimulation of Cortical Myosin Phosphorylation by p114RhoGEF Drives Cell Migration and Tumor Cell Invasion

Actinomyosin activity is an important driver of cell locomotion and has been shown to promote collective cell migration of epithelial sheets as well as single cell migration and tumor cell invasion. However, the molecular mechanisms underlying activation of cortical myosin to stimulate single cell movement, and the relationship between the mechanisms that drive single cell locomotion and those that mediate collective cell migration of epithelial sheets are incompletely understood. Here, we demonstrate that p114RhoGEF, an activator of RhoA that associates with non-muscle myosin IIA, regulates collective cell migration of epithelial sheets and tumor cell invasion. Depletion of p114RhoGEF resulted in specific spatial inhibition of myosin activation at cell-cell contacts in migrating epithelial sheets and the cortex of migrating single cells, but only affected double and not single phosphorylation of myosin light chain. In agreement, overall elasticity and contractility of the cells, processes that rely on persistent and more constant forces, were not affected, suggesting that p114RhoGEF mediates process-specific myosin activation. Locomotion was p114RhoGEF-dependent on Matrigel, which favors more roundish cells and amoeboid-like actinomyosin-driven movement, but not on fibronectin, which stimulates flatter cells and lamellipodia-driven, mesenchymal-like migration. Accordingly, depletion of p114RhoGEF led to reduced RhoA, but increased Rac activity. Invasion of 3D matrices was p114RhoGEF-dependent under conditions that do not require metalloproteinase activity, supporting a role of p114RhoGEF in myosin-dependent, amoeboid-like locomotion. Our data demonstrate that p114RhoGEF drives cortical myosin activation by stimulating myosin light chain double phosphorylation and, thereby, collective cell migration of epithelial sheets and amoeboid-like motility of tumor cells.     

Phytochemical Compounds from the Crop Byproducts of Tunisian Globe Artichoke Cultivars

The phytochemical composition in two Tunisian globe artichoke cultivars (bracts, leaves, and floral stems) was evaluated in the plant byproducts. The results indicated that the bracts contain the highest levels of total phenols, o‐diphenols, and flavonoids, whereas tannins seem to be more abundant in the leaves. Bracts from the ‘Violet d'Hyères’ cultivar possessed more total phenols (160.8 mg/g DW), flavonoids (64.9 mg/g DW), and anthocyanins (15.3 μg/g DW) than the ‘Blanc d'Oran’ bracts (134.5 mg/g DW, 51.2 mg/g DW, and 8.3 μg/g DW, resp.). Sixty‐four volatile compounds were identified in the headspace of globe artichoke material, particularly in the bracts. The volatile profile showed that sesquiterpene hydrocarbons and non‐terpene derivatives were the main volatiles emitted by the bracts in both cultivars. These results suggest that globe artichoke byproducts might represent a potential source of natural compounds, which could be used as nutraceuticals or as ingredients in the design of functional foods.     

Study of DYRK1B gene expression and its association with metabolic syndrome in a small cohort of Egyptians

Molecular Biology Reports - A cluster of many risk factors for type 2 diabetes and cardiovascular disease is used to describe the metabolic syndrome (MetS). Moreover, genetic differences associated...