Comparative analysis of organophosphate degrading enzymes from diverse species

Different types of organophosphorous compounds constitute most potent pesticides. These chemicals attack the nervous system of living organisms causing death. Different organisms produce enzymes to degrade these chemicals. These enzymes are present in simple microorganisms from archaea, bacteria to complex eukaryotes like humans. A comparison of representative eight shortlisted enzymes involved in the degradation and inactivation of organophosphates from a wide range of organisms was performed to infer the basis of their common functionality. There is little sequence homology in these enzymes which results in divergent tertiary structures. The only feature that these enzymes seem to share is their amino acid composition. However, structural analysis has shown no significant similarities among this functionally similar group of organophosphate degrading enzymes.     

Design and synthesis of 1,3-diarylurea derivatives as selective cyclooxygenase (COX-2) inhibitors

A group of 1,3-diarylurea derivatives, possessing a methylsulfonyl pharmacophore at the para-position of the N-1 phenyl ring, in conjunction with a N-3 substituted-phenyl ring (4-F, 4-Cl, 4-Me, 4-OMe), were designed and synthesized for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. In vitro COX-1/COX-2 isozyme inhibition structure-activity studies identified 1-(4-methylsulfonylphenyl)-3-(4-methoxyphenyl) urea (4e) as a potent COX-2 inhibitor (IC(50)=0.11 microM) with a high COX-2 selectivity index (SI=203.6) comparable to the reference drug celecoxib (COX-2 IC(50)=0.06 microM; COX-2 SI=405). The structure-activity data acquired indicate that the urea moiety constitutes a suitable scaffold to design new acyclic 1,3-diarylurea derivatives with selective COX-2 inhibitory activity.     

Brush cytology of gastric malignancies

OBJECTIVE: To compare endoscopic biopsy and cytology versus biopsy alone in the diagnosis of gastric malignancies. STUDY DESIGN: This prospective study included 229 cases referred for endoscopy for visible gastric lesions during a four-year period (1996-2000). Both biopsy and brush cytology were performed, and all the slides were screened by a cytotechnologist and reviewed by a pathologist. RESULTS: Of the 229 cases, 97 (42.4%) were proven to be malignant and 132 (57.6%) definitely benign. Biopsy was positive in 90 patients (92.7%), while brush cytology was positive in 85 (87.1%). Combined use of biopsy and brush cytology yielded higher diagnostic sensitivity (100%). CONCLUSION: Brush cytology is a safe, easy and rapid method of diagnosing gastric malignancies. Brush cytology is a useful adjunct in the diagnosis of gastric malignancies and should be considered a routine method in combination with biopsy. Multiple repeated endoscopies are recommended in cases of positive cytology and negative biopsy to rule out or confirm malignancy.     

BMP7‐induced dendritic growth in sympathetic neurons requires p75NTR signaling

Dendritic morphology is a critical determinant of neuronal connectivity, and in postganglionic sympathetic neurons, tonic activity correlates directly with the size of the dendritic arbor. Thus, identifying signaling mechanisms that regulate dendritic arborization of sympathetic neurons is important to understanding how functional neural circuitry is established and maintained in the sympathetic nervous system. Bone morphogenetic proteins (BMPs) promote dendritic growth in sympathetic neurons; however, downstream signaling events that link BMP receptor activation to dendritic growth are poorly characterized. We previously reported that BMP7 upregulates p75^NTR mRNA in cultured sympathetic neurons. This receptor is implicated in controlling dendritic growth in central neurons but whether p75^NTR regulates dendritic growth in peripheral neurons is not known. Here, we demonstrate that BMP7 increases p75^NTR protein in cultured sympathetic neurons, and this effect is blocked by pharmacologic inhibition of signaling via BMP type I receptor. BMP7 does not trigger dendritic growth in sympathetic neurons dissociated from superior cervical ganglia (SCG) of p75^NTR nullizygous mice, and overexpression of p75^NTR in p75^NTR?/? neurons is sufficient to cause dendritic growth even in the absence of BMP7. Morphometric analyses of SCG from wild‐type versus p75^NTR nullizygous mice at 3, 6, and 12 to 16 weeks of age indicated that genetic deletion of p75^NTR does not prevent dendritic growth but does stunt dendritic maturation in sympathetic neurons. These data support the hypotheses that p75^NTR is involved in downstream signaling events that mediate BMP7‐induced dendritic growth in sympathetic neurons, and suggest that p75^NTR signaling positively modulates dendritic complexity in sympathetic neurons in vivo. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1003–1013, 2016     

New approaches to modeling <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> inactivation by ultrasound

Ultrasound (US) is an effective technology to inactivate vegetative microorganisms in foods. In this study, the effect of amplitude levels (0.4, 7.5, and 37.5), duty cycles (0.3:0.7 s, 0.7:0.3 s, and 0.9: 0.1 s) and time (0, 2, 4, 6, 8, 10, 12, and 14 days) of US on inactivation of Staphylococcus aureus were investigated. In addition, genetic algorithm-artificial neural network (GA-ANN) and adaptive neuro-fuzzy inference system (ANFIS) models were used to predict inactivation of S. aureus. The GA-ANN and ANFIS were fed with three inputs of amplitude levels, duty cycles, and time. The inactivation rate of S. aureus was increased by increasing the amplitude levels, and the best inactivation was obtained at a 37.5 μm amplitude for which the S. aureus population was reduced to 2.59 CFU/mL. The high inactivation of S. aureus was achieved under a duty cycle of 0.7:0.3 s with reduction of the population to 1.49 CFU/mL. The developed GA-ANN, which included 17 hidden neurons, could predict the S. aureus population with a coefficient of determination of 0.986. The overall agreement between ANFIS predictions and experimental data was also very good (R ² ?=?0.979). Sensitivity analysis results showed that the amplitude level was the most sensitive factor for prediction of S. aureus.     

Size-Dependent Neurotoxicity of Aluminum Oxide Particles: a Comparison Between Nano- and Micrometer Size on the Basis of Mitochondrial Oxidative Damage

Aluminum nanoparticles (AlNPs) are among the most abundantly produced nanosized particles in the market. There is limited information about the potential harmful effects of aluminum oxide due to its particle size on human health. Considering the toxic effects of Al on brain as its target tissue, in this study, the toxicity of nanoparticles, microparticles, and ionic forms of Al on rat brain and isolated mitochondria was evaluated. Sixty male Wistar rats were divided into ten groups (six rats each), in which group I was the control, and the other groups were administered different doses of Al nanoparticles, Al microparticles (AlMP), and Al ionic forms (2, 4, and 8 mg/kg, i.p.) for 28 days. After 24 h, the animals were killed, brain tissue was separated, the mitochondrial fraction was isolated, and oxidative stress markers were measured. Also, mitochondrial function was assayed by MTT test. The results showed that all forms of Al particles induced ROS formation, lipid peroxidation, protein oxidation, glutathione depletion, mitochondrial dysfunction, and gait abnormalities in a dose-dependent manner. In addition, Al particles decreased mitochondrial membrane potential. These data indicated that oxidative stress might contribute to the toxicity effects of Al. Comparison of oxidative stress markers between all forms of Al revealed that the toxic effect of AlNP on brain tissue was substantially more than that caused by AlMP and bulk form. This study showed more neurotoxicity of AlNPs compared to other forms on brain oxidative damage that probably is due to more penetration into the brain.     

Micromorphological studies on Verbascum (Scrophulariaceae) in Iran with emphasis on seed surface, capsule ornamentation and trichomes

Seed micromorphology in 22 species, capsule surface in 28 species and capsule hairs in 20 species of genus Verbascum distributed in Iran were studied using scanning electron microscopy. The seed surface is ridged or alveolate among the studied species. Depth and density of the alveoli or ridges, size of polygonal cells along with arrangement of vesicles on the walls separating the polygonal cells on the seed surface seem to be species-specific in Verbascum. The capsule surface is striate, distinctly or indistinctly, or even smooth in Verbascum. The capsules are rarely glabrous (in V. orientale and V. intricatum), densely covered by branched hairs, or loosely by glandular hairs, depending on species. From the results of this study it is obvious that no correlation exists between the studied species concerning the micromorphological aspects studied here.     

Preparation of nanoliposomes linked to HER2/neu-derived (P5) peptide containing MPL adjuvant as vaccine against breast cancer

The study was aimed at evaluating antitumor and immunomodulatory effects of liposomal vaccine composed of P5 human epidermal growth factor receptor 2 (HER2)/neu-derived peptide coupled to the surface of high-temperature nanoliposomes containing distearoylphosphocholine:distearoylphosphoglycerol:Chol:dioleoylphosphatidylethanolamine (DOPE) comprising monophosphoryl lipid A (MPL) adjuvant in HER2/neu overexpressing the breast cancer model. BALB/c mice bearing TUBO carcinoma were subcutaneously immunized with formulations containing 10 µg P5 peptide and 25 µg MPL three times with 2-week intervals. To determine immuno responses in immunized mice, the amount of released interferon-γ and IL-4 were measured by the enzyme-linked immunospot method and the flow cytometric analysis on the isolated splenocytes. The results demonstrated that tumor-bearing mice immunized with Lip/DOPE/MPL/P5 formulation had the most released interferon-γ and the highest cytotoxic T lymphocyte responses that led to the lowest tumor size and the longest survival time than those of other formulations. The results achieved by Lip/DOPE/MPL/P5 formulation could make it a suitable candidate to induce effective antigen-specific tumor immunity against breast cancer.