Kynurenine 3-Monooxygenase gene associated with Nicotine initiation and addiction: Analysis of novel regulatory features at 5' and 3'-Regions

© 2018 Aziz, Abdel-Salam, Al-Obaide, Alobydi and Al-Humaish. Tobacco smoking is widespread behavior in Qatar and worldwide and is considered one of the major preventable causes of ill health and death. Nicotine is part of tobacco smoke that causes numerous health risks and is incredibly addictive; it binds to the α7 nicotinic acetylcholine receptor (α7nAChR) in the brain. Recent studies showed α7nAChR involvement in the initiation and addiction of smoking. Kynurenic acid (KA), a significant tryptophan metabolite, is an antagonist of α7nAChR. Inhibition of kynurenine 3-monooxygenase enzyme encoded by KMO enhances the KA levels. Modulating KMO gene expression could be a useful tactic for the treatment of tobacco initiation and dependence. Since KMO regulation is still poorly understood, we aimed to investigate the 5' and 3'-regulatory factors of KMO gene to advance our knowledge to modulate KMO gene expression. In this study, bioinformatics methods were used to identify the regulatory sequences associated with expression of KMO. The displayed differential expression of KMO mRNA in the same tissue and different tissues suggested the specific usage of the KMO multiple alternative promoters. Eleven KMO alternative promoters identified at 5'-regulatory region contain TATA-Box, lack CpG Island (CGI) and showed dinucleotide base-stacking energy values specific to transcription factor binding sites (TFBSs). The structural features of regulatory sequences can influence the transcription process and cell type-specific expression. The uncharacterized LOC105373233 locus coding for non-coding RNA (ncRNA) located on the reverse strand in a convergent manner at the 3'-side of KMO locus. The two genes likely expressed by a promoter that lacks TATA-Box harbor CGI and two TFBSs linked to the bidirectional transcription, the NRF1, and ZNF14 motifs. We identified two types of microRNA (miR) in the uncharacterized LOC105373233 ncRNA, which are like hsa-miR-5096 and hsa-miR-1285-3p and can target the miR recognition element (MRE) in the KMO mRNA. Pairwise sequence alignment identified 52 nucleotides sequence hosting MRE in the KMO 3' UTR untranslated region complementary to the ncRNA LOC105373233 sequence. We speculate that the identified miRs can modulate the KMO expression and together with alternative promoters at the 5'-regulatory region of KMO might contribute to the development of novel diagnostic and therapeutic algorithm for tobacco smoking

Light-Triggered Electron Transfer between a Conjugated Polymer and Cytochrome C for Optical Modulation of Redox Signaling

Protein reduction/oxidation processes trigger and finely regulate a myriad of physiological and pathological cellular functions. Many biochemical and biophysical stimuli have been recently explored to precisely and effectively modulate intracellular redox signaling, due to the considerable therapeutic potential. Here, we propose a first step toward an approach based on visible light excitation of a thiophene-based semiconducting polymer (P3HT), demonstrating the realization of a hybrid interface with the Cytochrome c protein (CytC), in an extracellular environment. By means of scanning electrochemical microscopy and spectro-electrochemistry measurements, we demonstrate that, upon optical stimulation, a functional interaction between P3HT and CytC is established. Polymer optical excitation locally triggers photoelectrochemical reactions, leading to modulation of CytC redox activity, either through an intermediate step, involving reactive oxygen species formation, or via a direct photoreduction process. Both processes are triggered by light, thus allowing excellent spatiotemporal resolution, paving the way to precise modulation of protein redox signaling

Nutritional status of Palestinian preschoolers in the Gaza Strip: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The authors examined factors associated with nutritional resilience/vulnerability among preschoolers in the Gaza Strip in 2007, where political violence and deprivation are widespread.</p> <p>Methods</p> <p>This cross-sectional study was carried out in 2007 using random sampling of kindergartens in order to select 350 preschoolers. Binary logistic regression was used to compare resilient (adequate nutrition) and vulnerable (stunted) groups with those with moderate nutrition.</p> <p>Results</p> <p>Approximately 37% of the subjects demonstrated nutritional resilience and 15% were vulnerable. Factors associated with nutritional resilience were child younger age, normal birth weight, actively hand- or spoon-feeding when the child was below two years, and residential stability in the past two years. The only factor associated with nutritional vulnerability was lower total score on the mother's General Health Questionnaire, which we interpret as a marker of maternal mental health.</p> <p>Conclusions</p> <p>Children with low-birth weight and older children had worse nutritional resiliency outcomes. Further, poorer outcomes for children were associated with lower maternal mental health status, as well as increased family residential instability. Our results add to the large literature on the pervasive effects of violence and instability on children and underscore the need for resources for early intervention and for the urgent resolution of the Palestinian and other armed conflicts.</p

Nile perch fish nuggets: Partial replacement of fish flesh with sesame hulls and sunroot — Quality assessment and storage stability

This study aimed to produce Nile perch fish nuggets by replacing a part of fish flesh with different concentrations of sesame hulls and sunroot to reach the optimal recipe. Chemical, microbiological, and sensory characteristics of nuggets were evaluated during 3 months of frozen storage at –18 °C. According to the obtained data on the chemical composition of raw materials, Nile perch flesh had the highest content of protein (20.21%), sesame hulls contained the highest amount of fat (13.54%), fiber (17.24%) and ash (16.11%), while sunroot tubers had the highest amount of carbohydrates (15.76%). Based on the sensory score, the acceptable replacement ratio for fish nuggets prepared with sunroot (T1) and sesame hulls (T2) was 10% and 7.5%, respectively. Thiobarbituric acid (TBA) analysis at zero time shows that the T1 samples had the minimum value compared to the T2 and control samples. During storage, the TBA levels increased slightly in all samples, but after three months T1 also showed the lowest value. The total plate count (TPC) and psychrophilic bacterial (PSY) count in the samples were affected by the period of frozen storage at –18 °C. The initial TPC and PSY loads were 2.32 and 2.02 log cfu/g for control; 2.24 and 1.72 log cfu/g for T1; 2.30 and 1.47 log cfu/g for T2, respectively. During storage, the values of TPC and Psy slightly decreased. In conclusion, this study succeeded in the replacement of Nile perch fish with sesame hulls and sunroot as new sources to improve the nutritional value and quality characteristics of fish nuggets.This study aimed to produce Nile perch fish nuggets by replacing a part of fish flesh with different concentrations of sesame hulls and sunroot to reach the optimal recipe. Chemical, microbiological, and sensory characteristics of nuggets were evaluated during 3 months of frozen storage at –18 °C. According to the obtained data on the chemical composition of raw materials, Nile perch flesh had the highest content of protein (20.21%), sesame hulls contained the highest amount of fat (13.54%), fiber (17.24%) and ash (16.11%), while sunroot tubers had the highest amount of carbohydrates (15.76%). Based on the sensory score, the acceptable replacement ratio for fish nuggets prepared with sunroot (T1) and sesame hulls (T2) was 10% and 7.5%, respectively. Thiobarbituric acid (TBA) analysis at zero time shows that the T1 samples had the minimum value compared to the T2 and control samples. During storage, the TBA levels increased slightly in all samples, but after three months T1 also showed the lowest value. The total plate count (TPC) and psychrophilic bacterial (PSY) count in the samples were affected by the period of frozen storage at –18 °C. The initial TPC and PSY loads were 2.32 and 2.02 log cfu/g for control; 2.24 and 1.72 log cfu/g for T1; 2.30 and 1.47 log cfu/g for T2, respectively. During storage, the values of TPC and Psy slightly decreased. In conclusion, this study succeeded in the replacement of Nile perch fish with sesame hulls and sunroot as new sources to improve the nutritional value and quality characteristics of fish nuggets

Biomechanical evolution of the Tkachev on uneven bars in female gymnastics

The development of joint kinematics and kinetics is fundamental to the successful performance of complex flight skills in gymnastics bar routines. Biomechanical understanding of these skills can provide coaches and scientists with key information to make training safe and effective. The Tkachev is a complex and popular gymnastics skill with many different variations. Recently, a new version has been performed, which has become popular with elite female performers. This study examined the key biomechanical characteristics of this skill and contrasted these to the earlier versions reported. Elite female gymnasts (n = 5) were recorded and manually digitised using twin video cameras (50 Hz) at the 2007 World Gymnastics Championships. Three-dimensional (3D) DLT was used to reconstruct the real world coordinates. Individualised inertia characteristics were calculated and used to determine mass centre kinematics. Inverse dynamics analysis was used to calculate joint kinetics at the hips and shoulders from the known values at the toes. The results of this study showed an increased flight time and rotational capacity during the aerial phase for the toe-on Tkachev, as well as a more simple movement pattern and joint kinetic demand with single power impulses at the hips and shoulders compared with previous versions. The key finding of this study was that the toe-on version appeared to be less physically demanding than that the inward and outward techniques, and provide the opportunity to perform more complex aerial phase body positions. These results can help coaches to physically prepare their gymnasts and biomechanists in terms of understanding the demands of these skills

Synthesis and antimicrobial activity of some penicillin and cephalosporin derivatives

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The Antidepressant Mirtazapine Inhibits Hepatic Innate Immune Networks to Attenuate Immune-Mediated Liver Injury in Mice

Activation of the innate immune system, including tissue macrophages and associated neutrophil infiltration, is an important driver of subsequent adaptive immune responses in many autoimmune diseases, including autoimmune hepatitis (AIH). The antidepressant mirtazapine has a unique complex pharmacology, altering signaling through a number of serotonin and histamine receptors that can impact macrophage function; an effect potentially influencing AIH outcome. In the mouse model of concanavalin A (Con A) induced liver injury (mimics many aspects of human AIH), in which early innate immune activation (i.e., stimulated hepatic macrophages/monocytes recruit neutrophils and additional monocytes to the liver) critically drives immune-mediated hepatitis induction, mirtazapine strikingly and dose-dependently inhibited Con A-induced liver injury. This inflammation-suppressing effect of mirtazapine was linked to an attenuation of Con A-stimulated early innate immune responses within the liver, including inhibition of hepatic macrophage/monocyte activation, decreased hepatic macrophage/monocyte-derived pro-inflammatory cytokine (e.g., TNFα) and chemokine (e.g., CXCL1 and CXCL2) production, suppression of Con A-induced increases in the hepatic expression of the neutrophil relevant endothelial cell adhesion molecule ICAM-1, with the resultant significant reduction in neutrophil recruitment into the liver. Consistent with our findings in the Con A model, mirtazapine also significantly reduced activation-induced release of cytokine/chemokine mediators from human CD14+ monocytes in vitro.Conclusion: Our data suggest that mirtazapine can attenuate hepatic innate immune responses that critically regulate the subsequent development of autoimmune liver injury. Therefore, given that it is a safe and widely used medication, mirtazapine may represent a novel therapeutic approach to autoimmune liver disease

Kinematic characteristics of elite men's 50 km race walking.

Race walking is an endurance event which also requires great technical ability, particularly with respect to its two distinguishing rules. The 50 km race walk is the longest event in the athletics programme at the Olympic Games. The aims of this observational study were to identify the important kinematic variables in elite men's 50 km race walking, and to measure variation in those variables at different distances. Thirty men were analysed from video data recorded during a World Race Walking Cup competition. Video data were also recorded at four distances during the European Cup Race Walking and 12 men analysed from these data. Two camcorders (50 Hz) recorded at each race for 3D analysis. The results of this study showed that walking speed was associated with both step length (r=0.54,P=0.002) and cadence (r=0.58,P=0.001). While placing the foot further ahead of the body at heel strike was associated with greater step lengths (r=0.45,P=0.013), it was also negatively associated with cadence (r= -0.62,P<0.001). In the World Cup, knee angles ranged between 175 and 186° at initial contact and between 180 and 195° at midstance. During the European Cup, walking speed decreased significantly (F=9.35,P=0.002), mostly due to a decrease in step length between 38.5 and 48.5 km (t=8.59,P=0.014). From this study, it would appear that the key areas a 50 km race walker must develop and coordinate are step length and cadence, although it is also important to ensure legal walking technique is maintained with the onset of fatigue

3-Chloro-4-methyl­quinolin-2(1H)-one

The title compound, C10H8ClNO, is almost planar (r.m.s. deviation for the 13 non-H atoms = 0.023 Å). In the crystal, inversion dimers linked by pairs of N—H⋯O hydrogen bonds generate R 2 2(8) rings. Weak aromatic π–π stacking inter­actions [centroid–centroid distance = 3.7622 (12) Å] also occur

Relativistic Brownian motion: From a microscopic binary collision model to the Langevin equation

The Langevin equation (LE) for the one-dimensional relativistic Brownian motion is derived from a microscopic collision model. The model assumes that a heavy point-like Brownian particle interacts with the lighter heat bath particles via elastic hard-core collisions. First, the commonly known, non-relativistic LE is deduced from this model, by taking into account the non-relativistic conservation laws for momentum and kinetic energy. Subsequently, this procedure is generalized to the relativistic case. There, it is found that the relativistic stochastic force is still \gd-correlated (white noise) but does \emph{no} longer correspond to a Gaussian white noise process. Explicit results for the friction and momentum-space diffusion coefficients are presented and discussed.Comment: v2: Eqs. (17c) and (28) corrected; v3: discussion extended, Eqs. (33) added, thereby connection to earlier work clarified; v4: final version, accepted for publication in Phys. Rev.