Optically active: microwave-assisted synthesis and characterization of L-lysine-derived poly (amide-imide)s

l-lysine hydrochloride was transformed to ethyl l-lysine dihydrochloride. This salt was reacted with trimellitic anhydride to yield the corresponding diacid (1). Microwave-assisted polycondensation results a series of novel Poly (amide-imide)s (PAI _a–i ). These polymers have inherent viscosities in the range of 0.23–0.66 dl g⁻¹, display optical activity from +8.02 to +15.11 (as there is no obvious regioselectivity between alpha and epsilon amino groups of the chiral diacid during the polymerization step then random orientation of diacid moieties along the polymer backbone can be predicted and the concept of “tacticity” cannot be addressed in this research), and are readily soluble in polar aprotic solvents. They start to decompose (T _10%) above 362°C and display glass-transition temperatures at 119–153°C. All of the above polymers were fully characterized by UV, FT-IR and ¹H NMR spectroscopy, elemental analysis, thermogravimetric analyses, DSC, inherent viscosity measurement and specific rotation.     

Prediction of 492 human protein kinase substrate specificities

Background

Complex intracellular signaling networks monitor diverse environmental inputs to evoke appropriate and coordinated effector responses. Defective signal transduction underlies many pathologies, including cancer, diabetes, autoimmunity and about 400 other human diseases. Therefore, there is high impetus to define the composition and architecture of cellular communications networks in humans. The major components of intracellular signaling networks are protein kinases and protein phosphatases, which catalyze the reversible phosphorylation of proteins. Here, we have focused on identification of kinase-substrate interactions through prediction of the phosphorylation site specificity from knowledge of the primary amino acid sequence of the catalytic domain of each kinase.

Results

The presented method predicts 488 different kinase catalytic domain substrate specificity matrices in 478 typical and 4 atypical human kinases that rely on both positive and negative determinants for scoring individual phosphosites for their suitability as kinase substrates. This represents a marked advancement over existing methods such as those used in NetPhorest (179 kinases in 76 groups) and NetworKIN (123 kinases), which consider only positive determinants for kinase substrate prediction. Comparison of our predicted matrices with experimentally-derived matrices from about 9,000 known kinase-phosphosite substrate pairs revealed a high degree of concordance with the established preferences of about 150 well studied protein kinases. Furthermore for many of the better known kinases, the predicted optimal phosphosite sequences were more accurate than the consensus phosphosite sequences inferred by simple alignment of the phosphosites of known kinase substrates.

Conclusions

Application of this improved kinase substrate prediction algorithm to the primary structures of over 23, 000 proteins encoded by the human genome has permitted the identification of about 650, 000 putative phosphosites, which are posted on the open source PhosphoNET website (http://www.phosphonet.ca).

     

Detection of a Cis [corrected] eQTL controlling BCMO1 gene expression leads to the identification of a QTG for chicken breast meat color

Classical quantitative trait loci (QTL) analysis and gene expression QTL (eQTL) were combined to identify the causal gene (or QTG) underlying a highly significant QTL controlling the variation of breast meat color in a F2 cross between divergent high-growth (HG) and low-growth (LG) chicken lines. Within this meat quality QTL, BCMO1 (Accession number GenBank: AJ271386), encoding the β-carotene 15, 15'-monooxygenase, a key enzyme in the conversion of β-carotene into colorless retinal, was a good functional candidate. Analysis of the abundance of BCMO1 mRNA in breast muscle of the HG x LG F2 population allowed for the identification of a strong cis eQTL. Moreover, reevaluation of the color QTL taking BCMO1 mRNA levels as a covariate indicated that BCMO1 mRNA levels entirely explained the variations in meat color. Two fully-linked single nucleotide polymorphisms (SNP) located within the proximal promoter of BCMO1 gene were identified. Haplotype substitution resulted in a marked difference in BCMO1 promoter activity in vitro. The association study in the F2 population revealed a three-fold difference in BCMO1 expression leading to a difference of 1 standard deviation in yellow color between the homozygous birds at this haplotype. This difference in meat yellow color was fully consistent with the difference in carotenoid content (i.e. lutein and zeaxanthin) evidenced between the two alternative haplotypes. A significant association between the haplotype, the level of BCMO1 expression and the yellow color of the meat was also recovered in an unrelated commercial broiler population. The mutation could be of economic importance for poultry production by making possible a gene-assisted selection for color, a determining aspect of meat quality. Moreover, this natural genetic diversity constitutes a new model for the study of β-carotene metabolism which may act upon diverse biological processes as precursor of the vitamin A.     

Acute effects of whole-body vibration on jump force and jump rate of force development: a comparative study of different devices

The goal of this study was to compare the acute effects of whole-body vibration (WBV) delivered by 3 devices with different mechanical behavior on jump force (JF) and jump rate of force development (JRFD). Twelve healthy persons (4 women and 8 men; age 30.5 ± 8.8 years; height 178.6 ± 7.3 cm; body mass 74.8 ± 9.7 kg) were exposed to WBV for 15 and 40 seconds using 2 professional devices (power plate [PP; vertical vibration] and Galileo 2000 [GA; oscillatory motion around the horizontal axis in addition to vertical vibration]) and a home-use device [Power Maxx, PM; horizontal vibration]). The JF and JRFD were evaluated before, immediately after, and 5 minutes after WBV. The JF measured immediately after 40 seconds of vibration by the GA device was reduced (3%, p = 0.05), and JRFD measured after 5 minutes of rest after 40 seconds of vibration by the PM device was reduced (12%, p < 0.05) compared with the baseline value. The acute effects of WBV (15 or 40 seconds) on JF and JRFD were not significantly different among the 3 devices. In conclusion, our hypothesis that WBV devices with different mechanical behaviors would result in different acute effects on muscle performance was not confirmed.     

Association of ebola virus matrix protein VP40 with microtubules

Viruses exploit a variety of cellular components to complete their life cycles, and it has become increasingly clear that use of host cell microtubules is a vital part of the infection process for many viruses. A variety of viral proteins have been identified that interact with microtubules, either directly or via a microtubule-associated motor protein. Here, we report that Ebola virus associates with microtubules via the matrix protein VP40. When transfected into mammalian cells, a fraction of VP40 colocalized with microtubule bundles and VP40 coimmunoprecipitated with tubulin. The degree of colocalization and microtubule bundling in cells was markedly intensified by truncation of the C terminus to a length of 317 amino acids. Further truncation to 308 or fewer amino acids abolished the association with microtubules. Both the full-length and the 317-amino-acid truncation mutant stabilized microtubules against depolymerization with nocodazole. Direct physical interaction between purified VP40 and tubulin proteins was demonstrated in vitro. A region of moderate homology to the tubulin binding motif of the microtubule-associated protein MAP2 was identified in VP40. Deleting this region resulted in loss of microtubule stabilization against drug-induced depolymerization. The presence of VP40-associated microtubules in cells continuously treated with nocodazole suggested that VP40 promotes tubulin polymerization. Using an in vitro polymerization assay, we demonstrated that VP40 directly enhances tubulin polymerization without any cellular mediators. These results suggest that microtubules may play an important role in the Ebola virus life cycle and potentially provide a novel target for therapeutic intervention against this highly pathogenic virus.     

Phloridzin reduces blood glucose levels and improves lipids metabolism in streptozotocin-induced diabetic rats

Phloridzin is the specific and competitive inhibition of sodium/glucose cotransporters in the intestine (SGLT1) and kidney (SGLT2). This property which could be useful in the management of postprandial hyperglycemia in diabetes and related disorders. Phloridzin is one of the dihydrochalcones typically contained in apples and in apple-derived products. The effect of phloridzin orally doses 5, 10, 20 and 40 mg/kg body weight on diabetes was tested in a streptozotocin-induced rat model of diabetes type 1. From beneficial effect of this compound is significant reduction of blood glucose levels and improve dyslipidemia in diabetic rats. As a well-known consequence of becoming diabetic, urine volume and water intake were significantly increased. Administration of phloridzin reduced urine volume and water intake in a dose-dependent manner. Phloretin decreases of food consumption, as well as a marked lowering in the weight. In conclusion, this compound could be proposed as an antihyperglycemic and antihyperlipidemic agent in diabetes and potential therapeutic in obesity.     

Ochratoxin A and aflatoxins in dried vine fruits from the Iranian market

Forty samples of dried vine fruit (raisin, n?=?22; currant, n?=?18) were collected in 2009?C2011 from the Iranian market. Aflatoxins (AFs) and ochratoxin A (OTA) were determined in these samples after immunoaffinity column clean-up by high performance liquid chromatography (HPLC) with fluorescence detection. The limit of quantification (LOQ) for AFs B₁. B₂, G₁, G₂, and OTA were 0.62, 0.50, 0.70, 0.40, and 0.42?ng/g, respectively. AFB₁ was found in one sample of raisin (0.64?ng/g) and in two samples of currant (0.20 and 0.63?ng/g). AFB₂ (0.33?ng/g) and AFG₂ (0.49?ng/g) were found in 2 samples of currant. OTA was detected in 3 of the 22 samples of raisin (mean 2.21?ng/g) and in one sample of currant (2.99?ng/g). The results show that in AFs and OTA levels are well below the regulatory limits both of the European Union and of Iran.     

Detection of Hepatozoon sp. in a Persian leopard (Panthera pardus ciscaucasica)

A free-ranging, adult, male Persian leopard (Panthera pardus ciscaucasica) was found at Geloul-Sarani protected zone, province of North-Khorasan, Iran and transported to the Ferdowsi University of Mashhad Veterinary Teaching Hospital. The leopard had normal temperature and respiratory and cardiac frequency, but was significantly dehydrated and had elevated capillary perfusion. The animal also was cachectic, with pale mucus membranes, third-eyelid protrusion, and bilaterally enlarged submandibular lymph nodes. The leopard was stabilized by intensive fluid and electrolyte therapy and hospitalized. In 2 days, the leopard had improved clinically but had severe ataxia and head pressing. Blood smears revealed gamonts of Hepatozoon sp. within some neutrophils. Hematologic and plasma chemistry abnormalities included moderate anemia, leukocytosis, hypocholestrolemia, and hypophosphatemia. In radiographic evaluations, no sign of periosteal reactions or new bone formation was seen on the skull, spine, long bones, pelvis, or vertebrae. The leopard was treated successfully with Tazocin and clindamycin for 1 mo. This is the first detection of a Hepatozoon sp. in wild Felidae in Iran. Because most Iranian wild felids and canids are endangered, knowing whether Hepatozoon infection represents a threat for these animals is important.     

Human endometrial stem cell neurogenesis in response to NGF and bFGF

The potential of cell therapy is promising in nerve regeneration, but is limited by ethical considerations about the proper and technically safe source of stem cells. We report the successful differentiation of human EnSCs (endometrial stem cells) as a rich source of renewable and safe progenitors into high-efficiency cholinergic neurons. The extracellular signals of NGF (nerve growth factor) and bFGF (basic fibroblast growth factor) could induce cholinergic neuron differentiation. ChAT (choline acetyltransferase), MAP2 (microtubule associated protein 2) and NF-l (neurofilament L) increased after administration of bFGF and NGF to the EnSC cultures. trkC and FGFR2 (fibroblast growth factor receptor 2), which belong to the NGF and bFGF receptors respectively, were determined in populations of EnSCs. NGF, bFGF and their combination differentially influenced human EnSCs high efficiency differentiation. By inducing cholinergic neurons from EnSCs in a chemically defined medium, we could produce human neural cells without resorting to primary culture of neurons. This in vitro method provides an unlimited source of human neural cells and facilitates clinical applications of EnSCs for neurological diseases.     

Glutathione mediated reductive activation and mitochondrial dysfunction play key roles in lithium induced oxidative stress and cytotoxicity in liver

Lithium preparations are commonly used drug in treating mental disorders and bipolar diseases, but metal's cytotoxic mechanisms have not yet been completely understood. In this study, we investigated the cytotoxic mechanisms of lithium in freshly isolated rat hepatocytes. Lithium cytotoxicity were associated with reactive oxygen species (ROS) formation and collapse of mitochondrial membrane potential and cytochrome c release into the hepatocyte cytosol. All of the mentioned lithium-induced cytotoxicity markers were significantly (P?相似文献