Density-functional-theory approach to the Hamiltonian adaptive resolution simulation method.

In the Hamiltonian adaptive resolution simulation method (H-AdResS) it is possible to simulate coexisting atomistic (AT) and ideal gas representations of a physical system that belong to different subdomains within the simulation box. The Hamiltonian includes a field that bridges both models by smoothly switching on (off) the intermolecular potential as particles enter (leave) the AT region. In practice, external one-body forces are calculated and applied to enforce a reference density throughout the simulation box, and the resulting external potential adds up to the Hamiltonian. This procedure suggests an apparent dependence of the final Hamiltonian on the system's thermodynamic state that challenges the method's statistical mechanics consistency. In this paper, we explicitly include an external potential that depends on the switching function. Hence, we build a grand canonical potential for this inhomogeneous system to find the equivalence between H-AdResS and density functional theory (DFT). We thus verify that the external potential inducing a constant density profile is equal to the system's excess chemical potential. Given DFT's one-to-one correspondence between external potential and equilibrium density, we find that a Hamiltonian description of the system is compatible with the numerical implementation based on enforcing the reference density across the simulation box. In the second part of the manuscript, we focus on assessing our approach's convergence and computing efficiency concerning various model parameters, including sample size and solute concentrations. To this aim, we compute the excess chemical potential of water, aqueous urea solutions and Lennard-Jones (LJ) mixtures. The results' convergence and accuracy are convincing in all cases, thus emphasising the method's robustness and capabilities.

Detection of novel mitochondrial mutations in cytochrome C oxidase subunit 1 (COX1) in patients with familial adenomatous polyposis (FAP).

BACKGROUND: Familial adenomatous polyposis (FAP) is an Autosomal dominant inherited disorder and a rare form| of colorectal cancer (CRC) that is characterized by the development of hundreds to thousands of adenomas in the rectum and colon. Mostly, cancers develop after the advent of the polyps. It appears in both sexes evenly, and the occurrence of the disease is in the second decade of life. Mitochondrial genome mutations have been reported with a variety of Tumors, but the precise role of these mutations in the pathogenicity and tumor progression is not exactly clear. Cytochrome c oxidase subunit I (COX1) is the terminal enzyme of the mitochondrial respiratory chain. The present study aims at assessing the occurrence of mtDNA mutations in COX1 gene in FAP patients and attempts to find out the cause and effect relationship between mitochondrial mutations and tumor progression. METHODS: In this study, 56 FAP patients were investigated for the presence of the mutations in mitochondrial COX1 coding gene by PCR and sequencing analysis. All sequences that differed from the revised Cambridge Reference Sequence (rCRS) were classified as missense/ nonsense or silent mutations. Functional genomic studies using Bio-informatics tools were performed on the founded mutations to understand the downstream alterations in structure and function of protein. RESULTS: We identified 38 changes in the COX1 gene in patients with FAP symptoms. Most of them were heteroplasmic changes of missense type (25/38). Tree of the changes (G6145A, C6988A, and T7306G) were nonsense mutations and had not been reported in the literature before. Our results of bioinformatics predictions showed that the identified mutations can affect mitochondrial functions, especially if the conservative domain of the protein is concerned. CONCLUSION: Our findings indicate a high frequency of mtDNA mutations in all of the FAP cases compared to matched controls. These data significantly enhance our understanding of how such mutations contribute to cancer pathologies and develop the cancer treatment methods by new diagnostic biomarkers, and new drugs for gene therapy.

Evaluation of the substitutions in 212, 342 and 215 amino acid positions in binding site of organophosphorus acid anhydrolase using the molecular docking and laboratory analysis.

OBJECTIVE: Organophosphorus Acid Anhydrolase (OPAA) is used as one of the most important enzymes in the decontamination process of organophosphate compounds. In this study, we aimed to evaluate the effects of amino acid substitution in OPAA's substrate-binding site on its catalytic activity using the rational engineering strategy. METHODS: The native and three mutant forms of OPAA enzyme including 4ZWP, 4ZWU and Mut6 were studied using the docking technique toward parathion, paraoxon and R-VX compounds. Furthermore, enzyme assay was performed on the native OPAA and Mut6 toward parathion. RESULTS: Docking results showed a decreased catalytic activity of the mutant forms toward parathion and paraoxon. Furthermore, enzyme assay showed in accordance with docking results a decreased activity of Mut6 compared to the native form. The results of docking prediction for R-VX showed an increased catalytic activity of 4ZWP and 4ZWU. 4ZWU had the highest activity, while the activity of Mut6 was lower than the native form. CONCLUSION: Amino acid positions of 212 and 342 seem to be important sites in the small pocket of OPAA affecting the enzyme catalytic activity. Therefore, substitution of these sites with appropriate amino acids depending on the substrate structure, can affect the enzyme catalytic efficiency (Tab. 2, Fig. 3, Ref. 30).

Role of Natural Flocculation in Eliminating Toxic Metals.

Metals as the most common environmental pollutants derive from different sources and have far-reaching harmful impacts on flora, fauna and human health. Moreover, metals cause irreversible damages to marine ecosystems. Estuaries are most productive ecosystems for living creatures and act as a transporting corridor for exchanging materials from river to water bodies including oceans, seas and lakes. One of the most important processes in this region is flocculation. Not only does flocculation process convert a huge percentage of metals from dissolved phase to particulate phase in providing micronutrients to aquatic organisms, more importantly, but it also eliminates metals from aquatic ecosystems and gives aid to the pollution of water bodies to be on the decrease. Moreover, the chemical mass balance between river and sea is substantially influenced by flocculation process. Salinity, pH, dissolved oxygen, dissolved organic carbon and sodium hypochlorite as important factors affect the flocculation of metals during estuarine mixing of river water with seawater. It is vital to make use of natural processes in eliminating pollutants. Thus, natural processes need to be recognized and promoted by various means.

Broadband wide-angle polarization-insensitive metasurface solar absorber.

In this paper, a new ultra-thin and broadband wide-angle polarization-insensitive metasurface solar absorber is designed and optimized. The proposed metasurface absorber topology is optimized by using a genetic algorithm to enhance the bandwidth and decrease the unit cell area. The proposed unit cell is designed with fourfolded symmetric subunit cells rotated in the clockwise direction to achieve a polarization-independent response. The unit cell with 320×320 nm2 area and 50 nm thickness has a broadband (≥90%) absorption response in the visible frequency region of the solar spectrum and infrared from 350 THz to 700 THz for normal incident angles and higher than 70% for incident angles up to 40° at both polarizations.

Evaluation of the spatial arrangement of Purkinje cells in ataxic rat's cerebellum after Sertoli cells transplantation.

BACKGROUND: Purkinje cells (PCs) pathology is important in cerebellar disorders like ataxia. The spatial arrangement of PCs after different treatments has not been studied extensively. Immunohistochemistry (IHC) analysis of cerebellum can give a proper tool for explaining the pathophysiology of PCs in ataxia. Here we stereologically analysed the 3-dimensional spatial arrangement of PCs in the cerebellum of rats after ataxia induction with 3-acetylpyridine (3-AP). MATERIALS AND METHODS: Ataxia was induced in rats by intraperitoneal injection of 3-AP (65 mg/kg). Spatial arrangement of PCs for differences in ataxic rats with (3-AP-SC) or without (3-AP) Sertoli cells (SCs) transplantation was evaluated using second-order stereology. The IHC method by using antibodies to anti-calbindin in the cerebellum was applied. RESULTS: Our results showed that a random arrangement is at larger distances between PCs in 3-AP and 3-Ap-SC groups. Therefore the PCs are not normally arranged after 3-AP and SCs transplantation stored the spatial arrangements of the cells after ataxia induction in rats. IHC analyse shows that number of PCs was significantly improved after the SC transplantation. CONCLUSIONS: Segregation of PCs can be observed at some areas in the ataxic rats' cerebellum. However, the spatial arrangement of PCs was unchanged in SCs transplanted rats. (Folia Morphol 2018; 77, 2: 194-200).

The melatonin immunomodulatory actions in radiotherapy.

Radiotherapy has a key role in cancer treatment in more than half of patients with cancer. The management of severe side effects of this treatment modality is a limiting factor to appropriate treatment. Immune system responses play a pivotal role in many of the early and late side effects of radiation. Moreover, immune cells have a significant role in tumor response to radiotherapy, such as angiogenesis and tumor growth. Melatonin as a potent antioxidant has shown appropriate immune regulatory properties that may ameliorate toxicity induced by radiation in various organs. These effects are mediated through various modulatory effects of melatonin in different levels of tissue reaction to ionizing radiation. The effects on the DNA repair system, antioxidant enzymes, immune cells, cytokines secretion, transcription factors, and protein kinases are most important. Moreover, anti-cancer properties of melatonin may increase the therapeutic ratio of radiotherapy. Clinical applications of this agent for the management of malignancies such as breast cancer have shown promising results. It seems anti-proliferative, anti-angiogenesis, and stimulation or suppression of some immune cell responses are the main anti-tumor effects of melatonin that may help to improve response of the tumor to radiotherapy. In this review, the effects of melatonin on the modulation of immune responses in both normal and tumor tissues will be discussed.

Template synthesis of maghemite nanoparticle in carboxymethyl cellulose and its application for electrochemical cabergoline sensing.

Maghemite (γ-Fe2O3) nanoparticles were produced via coprecipitation onto carboxymethyl cellulose matrix based templates followed by calcination. The resulting maghemite nanoparticles were characterized by Fourier transform infrared spectra, X-ray diffraction, scanning electron microscopy and transmission electron microscopy. The magnetization measurement of as-synthesized γ-Fe2O3 displayed superparamagnetic characteristics at room temperature. Then, a novel maghemite nanoparticles carbon paste modified electrode was developed for determination of cabergoline. The modified electrode has an outstanding catalytic effect on the oxidation current of cabergoline and the mechanism was studied using cyclic voltammetry. The oxidation peak current was proportional to the concentration of cabergoline from 1×10-7 to 3.5×10-5molL-1 with a detection limit of 3×10-8molL-1 at signal to noise ratio of 3. The proposed method was examined as a selective, simple and precise method for voltammetric determination of cabergoline in plasma and pharmaceutical samples.

Evaluation of the sensitivity and specificity of serum level of prostasin, CA125, LDH, AFP, and hCG+ß in epithelial ovarian cancer patients.

OBJECTIVES: The aim of this work was to compare and analyze the diagnostic value of serum prostasin, cancer antigen 125 (CA125), lactate dehydrogenase (LDH), alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG+ß) in epithelial ovarian cancer (EOC) and evaluate if their serum levels could be used as a potential diagnostic markers of EOC from benign tumors and healthy women. MATERIALS AND METHODS: Preoperative serum samples of 110 women (24 healthy controls, 66 ovarian benign tumors, and 20 EOC) were tested for prostasin, CA125, AFP, and hCG+ß. The level of CA125, AFP, and hCG+ß serum tumor markers were determined by electro-chemiluminescence immunoassay (ECLIA) and the serum level of prostasin was measured using enzyme-linked immunosorbent assay (ELISA) and LDH activity was measured by spectrophotometer and analyzed using SPSS version. RESULTS: The Area Under the Curve (AUC) values of prostasin, CA125, LDH, AFP, and hCG+ß for the discrimination of EOC from benign and healthy controls were, respectively, 0.89, 0.91, 0.77, 0.54, and 0.65, and significant increase in serum levels of prostasin, CA125, and LDH were observed for EOC compared with benign and control groups. CONCLUSION: The present study showed that CA 125 and LDH levels of serum increased in high stages, while prostasin level was decreased in high stages. The present results indicate that prostasin, CA125, and LDH are differentially expressed in EOC than in benign and healthy control population, that may be an indicative of a better diagnostic value, with higher sen- sitivity and specificity. Here the authors used a multimarker approach, consisting of CA125, AFP, beta hCG, prostasin, and LDH that could provide a more accurate tool for a differential diagnosis of patients with EOC.

Association between the C34T polymorphism of the AMPD1 gene and essential hypertension in Malaysian patients.

The aim of this study was to determine whether C34T, a common polymorphism of the adenosine monophosphate deaminase 1 gene (AMPD1), is associated with essential hypertension (EH). We hypothesize that C34T is associated with the development of EH. A case-control design was used for this study. The DNA was extracted using a commercial kit from the whole blood of 200 patients with hypertension and 200 subjects without hypertension from selected Malaysian ethnicities (Malays, Chinese, and Indians). Polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) and agarose gel electrophoresis were used for genotyping. The C34T gene polymorphism of AMPD1 was significantly associated with EH in the Malaysian subjects (P < 0.0001). The genotype frequencies of CC, CT, and TT were 6%, 79%, and 15%, respectively, among hypertensive subjects, while no TT genotypes were observed in the normotensive subjects. Further, the frequency of hypertension was higher among T allele carriers than C carriers (OD = 9.94; 95%CI = 6.851-14.434). There were significant differences in the systolic blood pressure, diastolic blood pressure, and pulse pressure (P ˂ 0.05) between the normotensive and hypertensive Malaysian subjects; we believe those difference were caused by the C34T polymorphism. For the first time in Malaysia, the current study provides evidence that a common polymorphism of the AMPD1 gene (C34T) is strongly associated with EH.

Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features.

The 'neurodegeneration with brain iron accumulation' (NBIA) disease family entails movement or cognitive impairment, often with psychiatric features. To understand how iron loading affects the brain, we studied mice with disruption of two iron regulatory genes, hemochromatosis (Hfe) and transferrin receptor 2 (Tfr2). Inductively coupled plasma atomic emission spectroscopy demonstrated increased iron in the Hfe-/- × Tfr2mut brain (P=0.002, n ≥5/group), primarily localized by Perls' staining to myelinated structures. Western immunoblotting showed increases of the iron storage protein ferritin light polypeptide and microarray and real-time reverse transcription-PCR revealed decreased transcript levels (P<0.04, n ≥5/group) for five other NBIA genes, phospholipase A2 group VI, fatty acid 2-hydroxylase, ceruloplasmin, chromosome 19 open reading frame 12 and ATPase type 13A2. Apart from the ferroxidase ceruloplasmin, all are involved in myelin homeostasis; 16 other myelin-related genes also showed reduced expression (P<0.05), although gross myelin structure and integrity appear unaffected (P>0.05). Overlap (P<0.0001) of differentially expressed genes in Hfe-/- × Tfr2mut brain with human gene co-expression networks suggests iron loading influences expression of NBIA-related and myelin-related genes co-expressed in normal human basal ganglia. There was overlap (P<0.0001) of genes differentially expressed in Hfe-/- × Tfr2mut brain and post-mortem NBIA basal ganglia. Hfe-/- × Tfr2mut mice were hyperactive (P<0.0112) without apparent cognitive impairment by IntelliCage testing (P>0.05). These results implicate myelin-related systems involved in NBIA neuropathogenesis in early responses to iron loading. This may contribute to behavioral symptoms in NBIA and hemochromatosis and is relevant to patients with abnormal iron status and psychiatric disorders involving myelin abnormalities or resistant to conventional treatments.

The Association Between Blood Pressure and Normal Range Thyroid Function Tests in a Population Based Tehran Thyroid Study.

Several studies have shown an association between overt hypothyroidism and diastolic hypertension. Association between subclinical hypothyroidism and hypertension is a matter of debate. The aim of this study was to examine the association of systolic and diastolic blood pressure, pulse pressure and mean arterial blood pressure with serum thyroid hormones levels in euthyroid subjects.Data from 4 756 individuals of the Tehran Thyroid study (TTS) without any previously known thyroid disease were analyzed. We divided participants based on TSH tertiles. Serum TSH and free T4 (FT4) concentration, systolic blood pressure (SBP), diastolic blood pressure (BPD) body mass index (BMI) were measured in all subjects.Among 5 786 individuals participated, 4 985 were euthyroid. After implementing exclusion criteria, 4 756 individuals remained of whom 2 122 (44.6%) were male and 2 634 (55.4%) were female. Multiple linear regression analysis revealed no association between TSH levels within reference ranges and blood pressure profile. No significant relationship was observed between TSH levels and systolic or diastolic blood pressure or the mean arterial pressure or pulse pressure in each tertile of TSH. There was a negative association between pulse pressure and TSH in the second tertile (r=- 0.066, p=0.009). Regression analysis showed that FT4 was significantly associated with systolic blood pressure, diastolic blood pressure, pulse pressure and mean arterial pressure.No association was found between serum TSH and blood pressure profile in euthyroid subjects. Serum FT4 levels showed a positive association with blood pressure profiles.

Photothermal cancer therapy by gold-ferrite nanocomposite and near-infrared laser in animal model.

Surface plasmon resonance effect of gold nanostructures makes them good candidates for photothermal therapy (PTT) application. Herein, gold-ferrite nanocomposite (GFNC) was synthesized and characterized as a photothermal agent in PTT. The aim of this study was to investigate the effect of GFNC upon laser irradiation on treatment of cancer in mice bearing melanoma cancer. Thirty mice received 1.5 × 10(6) B16/F10 cells subcutaneously. After 1 week, the mice bearing solid tumor were divided into four groups: control group (without any treatment), laser group (received laser irradiation without GFNC injection), GFNC group (only received intratumorally GFNC), and GFNC + laser group (received intratumorally GFNC upon laser irradiation). In GFNC + laser group, 200 µL of fluid, 1.3 × 10(-7) mol L(-1) gold nanoparticles, was injected intratumorally and immediately the site of tumor was exposed to continuous wave diode laser beam (808 nm, 1.6 W cm(-2)) for 15 min. All mice but four were euthanized 24 h after treatment to compare the necrotic surface area histologically by using measuring graticule. Statistical analyses revealed significant differences in necrosis extent for GFNC + laser group, compared to other groups. Four subjects (control group and GFNC + laser group, two mice each) were kept for longitudinal study. Histological analyses and tumor volume measurements of the four subjects indicated that tumor in GFNC + laser group was controlled appropriately. It was concluded that combining an 808-nm laser at a power density of 1.6 W cm(-2) with GFNC has a destruction effect in melanoma cancer cells in an animal model.

The effects of intra-dorsal hippocampus infusion of pregnenolone sulfate on memory function and hippocampal BDNF mRNA expression of biliary cirrhosis-induced memory impairment in rats.

Learning and memory impairment is one of the most challenging complications of cirrhosis and present treatments are unsatisfactory. The exact mechanism of cirrhosis cognitive dysfunction is unknown. Pregnenolone sulfate (PREGS) is an excitatory neurosteroid that acts as a N-methyl-D-aspartate (NMDA) receptor agonist and GABAA receptor antagonist. In this study we evaluated the effect of intra CA1 infusion of PREGS on cirrhotic rats' memory function using the Y-maze test. Hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression was also evaluated. Three weeks after bile duct ligation (BDL) surgery, rats were under stereotaxic surgery for insertion of two guide cannulas in the CA1 region of the hippocampus. After 1-week of recovery, PREGS was administered through CA1 cannulas in cirrhotic rats, while control or sham groups received vehicle. For evaluation of NMDA receptor role in memory-enhancing effects of PREGS, DL-2-Amino-5-phosphonopentanoic acid (AP5) which is a potent and competitive antagonist of NMDA receptor, co-administered with PREGS and for assessment of hippocampal BDNF mRNA expression, quantitative Real-time reverse transcriptase-PCR (RT-PCR) was used. Results showed that 28 days after BDL, cirrhotic animals' memory significantly decreased in comparison with control and sham groups, while PREGS infusion could restore memory impairment (P<0.05). PREGS effects on memory of cirrhotic rats were antagonized by DAP5. RT-PCR findings have shown that hippocampal relative BDNF mRNA expression was up-regulated in PREGS-treated groups in comparison with the BDL group (P<0.001). Our findings suggest that PREGS has a memory-enhancing effect in cirrhosis memory deficit in acute therapy and this effect may be through NMDA (glutamate) receptor involvement and BDNF mRNA expression.

Dextrin-coated zinc substituted cobalt-ferrite nanoparticles as an MRI contrast agent: In vitro and in vivo imaging studies.

Application of superparamagnetic iron oxide nanoparticles (NPs) as a negative contrast agent in magnetic resonance imaging (MRI) has been of widespread interest. These particles can enhance contrast of images by altering the relaxation times of the water protons. In this study, dextrin-coated zinc substituted cobalt-ferrite (Zn0.5Co0.5Fe2O4) NPs were synthesized by a co-precipitation method, and the morphology, size, structure and magnetic properties of the NPs were investigated. These NPs had superparamagnetic behavior with an average size of 3.9 (±0.9, n=200)nm measured by transmission electron microscopy. Measurements on the relaxivities (r2 and r2(*)) of the NPs were performed in vitro by agarose phantom. In addition, after subcutaneous injection of the NPs into C540 cell line in C-57 inbred mice, the relaxivities were measured in vivo by a 1.5T MRI system. These NPs could effectively increase the image contrast in both T2-and T2(*)-weighted samples.

Continuous neural network with windowed Hebbian learning.

We introduce an extension of the classical neural field equation where the dynamics of the synaptic kernel satisfies the standard Hebbian type of learning (synaptic plasticity). Here, a continuous network in which changes in the weight kernel occurs in a specified time window is considered. A novelty of this model is that it admits synaptic weight decrease as well as the usual weight increase resulting from correlated activity. The resulting equation leads to a delay-type rate model for which the existence and stability of solutions such as the rest state, bumps, and traveling fronts are investigated. Some relations between the length of the time window and the bump width is derived. In addition, the effect of the delay parameter on the stability of solutions is shown. Also numerical simulations for solutions and their stability are presented.

Endocarditis associated with Erysipelothrix rhusiopathiae in a fat-tailed ram.

Endocarditis is rarely reported in sheep and information presented for ovine endocarditis is based mostly on comparative findings in the cattle. Infective vegetative endocarditis of the right heart was diagnosed in a 3-year-old fat-tailed ram. Clinical findings included tachycardia, marked brisket edema, jugular veins distention and pulsation and pale mucous membranes. Hematologic abnormality included neutrophilic leukocytosis. Necropsy confirmed severe right atrioventricular and pulmonary valves vegetative endocarditis with evidence of right heart failure. Erysipelothrix rhusiopathiae was isolated from those vegetative lisions.