The Effect of Abamectin on Locusta Migratoria Neurosecretory Cells and Mid Gut, Using Ultrastructure Examination, Oxidative Stress Study, and In-Silico Molecular Docking.

(1) Background: Few studies have been carried out to appraise abamectin toxicity toward Locusta migratoria nymphs. (2) Methods: This study aimed to evaluate the cytotoxic effect of abamectin as an insecticide through examining the changes and damage caused by this drug, in both neurosecretory cells and midgut, using L. migratoria nymphs as a model of the cytotoxic effect. Histopathological change in the brain was examined in both normal and abamectin-treated fifth-instar nymphs. Neurosecretory cells (NSCs) were also examined where there were loosely disintegrated cells or vacuolated cytoplasm. (3) Results: The results showed distinct histological changes in the gastrointestinal tract of L. migratoria nymphs treated with abamectin, with significant cellular damage and disorganization, i.e., characteristic symptoms of cell necrosis, a destroyed epithelium, enlarged cells, and reduced nuclei. The observed biochemical changes included an elevation in all measured oxidative stress parameters compared to untreated controls. The malondialdehyde activities (MDAs) of the treated nymphs had a five- to six-fold increase, with a ten-fold increase in superoxide dismutase (SOD), nine-fold increase in glutathione-S-transferase (GST), and four-fold increase in nitric oxide (NO). (4) Conclusions: To further investigate the theoretical method of action, a molecular docking simulation was performed, examining the possibility that abamectin is an inhibitor of the fatty acid-binding protein Lm-FABP (2FLJ) and that it binds with two successive electrostatic hydrogen bonds.

Analysis of G-quadruplex forming sequences in podocytes-marker genes and their potential roles in inherited glomerular diseases.

Nephrotic Syndrome is the most widespread pediatric kidney disorder. Genetic alterations in podocyte genes are thought to be responsible for the disease. G-quadruplexes are non-conventional guanine-rich DNA and RNA structures, which are commonly found in regulatory regions. This study examined the potential G-quadruplexes forming sequences in the promoters and gene bodies of podocyte-marker genes. High G-quadruplexes density was found in the vascular endothelial growth facto, cluster of differentiation-151, integrin subunit beta-4, metalloendopeptidase, Wilms tumor-1, integrin subunit beta-3, synaptopodin, and nephrin promoters. Vascular endothelial growth facto, cluster of differentiation-151 and integrin subunit beta-4 had the highest G-quadruplexes density in their gene bodies and promoters. Additionally, highly stable G-quadruplexes forming sequences were identified within all podocyte-marker genes. Furthermore, it is hypothesized that Wilms tumor-1 is capable of controlling the transcription of podocalyxin by binding to two possible G-quadruplexes forming motifs. We next analyzed the most frequently reported genetic mutations in the selected genes for their effect on DNA G-quadruplexes formation, and the thermodynamic stability of predicted RNA G-quadruplexes, using RNAfold. Importantly, the missense mutation c.121_122del in the nephrin gene reported in patients with NS type 1 affected DNA G-quadruplexes formation in this region as well as the thermodynamic stability of the corresponding RNA G-quadruplexes. Overall, we report the potential regulatory roles of G-quadruplexes in the etiology of nephrotic syndrome and their possible use as drug targets to treat kidney diseases.

G-quadruplex forming sequences in the genes coding for cytochrome P450 enzymes and their potential roles in drug metabolism.

The majority of drugs are metabolized by cytochrome P450 (CYP) enzymes, primarily belonging to the CYP1, CYP2 and CYP3 families. Genetic variations are the main cause of inter-individual differences in drug response, which constitutes a major concern in pharmacotherapy. G-quadruplexes (G4s), are non-canonical DNA and RNA secondary structures formed by guanine-rich sequences. G4s have been implicated in cancer and gene regulation. In this study, we investigated putative G4-forming sequences (PQSs) in the CYP genes. Our findings reveal a high density of PQSs in the full genes of CYP family 2. Moreover, we observe an increased density of PQSs in the promoters of CYP family 1 genes compared to non-CYP450 genes. Importantly, stable PQSs were also identified in all studied CYP genes. Subsequently, we assessed the impact of the most frequently reported genetic mutations in the selected genes and the possible effect of these mutations on G4 formation as well as on the thermodynamic stability of predicted G4s. We found that 4 SNPs overlap G4 sequences and lead to mutated DNA and RNA G4 forming sequences in their context. Notably, the mutation in the CYP2C9 gene, which is associated with impaired (S)-warfarin metabolism in patients, alters a G4 sequence. We then demonstrated that at least 10 of the 13 chosen cytochrome P450 G4 candidates form G-quadruplex structures in vitro, using a combination of spectroscopic methods. In conclusion, our findings indicate the potential role of G-quadruplexes in the regulation of cytochrome genes, and emphasize the importance of G-quadruplexes in drug metabolism.

Bio-guided isolation of potential anti-inflammatory constituents of some endophytes isolated from the leaves of ground cherry (Physalis pruinosa L.) via ex-vivo and in-silico studies.

BACKGROUND: Due to the extensive potential of previously studied endophytes in addition to plants belonging to genus Physalis as a source of anti-inflammatory constituents, the present study aimed at isolation for the first time some endophytic fungi from the medicinal plant Physalis pruinosa. METHODS: The endophytic fungi were isolated from the fresh leaves of P. pruinosa then purified and identified by both morphological and molecular methods. Comparative evaluation of the cytotoxic and ex vivo anti-inflammatory activity in addition to gene expression of the three pro-inflammatory indicators (TNF-α, IL-1ß and INF-γ) was performed in WBCs treated with lipopolysaccharide (LPS) for the identified endophytes, isolated compounds and the standard anti-inflammatory drug (piroxicam). For prediction of the binding mode of the top-scoring constituents-targets complexes, the Schrödinger Maestro 11.8 package (LLC, New York, NY) was employed in the docking study. RESULTS: A total of 50 endophytic fungal isolates were separated from P. pruinosa leaves. Selection of six representative isolates was performed for further bioactivity screening based on their morphological characters, which were then identified as Stemphylium simmonsii MN401378, Stemphylium sp. MT084051, Alternaria infectoria MT573465, Alternaria alternata MZ066724, Alternaria alternata MN615420 and Fusarium equiseti MK968015. It could be observed that A. alternata MN615420 extract was the most potent anti-inflammatory candidate with a significant downregulation of TNF-α. Moreover, six secondary metabolites, alternariol monomethyl ether (1), 3'-hydroxyalternariol monomethyl ether (2), alternariol (3), α-acetylorcinol (4), tenuazonic acid (5) and allo-tenuazonic acid (6) were isolated from the most potent candidate (A. alternata MN615420). Among the tested isolated compounds, 3'-hydroxyalternariol monomethyl ether showed the highest anti-inflammatory potential with the most considerable reductions in the level of INF-γ and IL-1ß. Meanwhile, alternariol monomethyl ether was the most potent TNF-α inhibitor. The energy values for the protein (IL-1ß, TNF-α and INF-γ)-ligand interaction for the best conformation of the isolated compounds were estimated using molecular docking analysis. CONCLUSIONS: The results obtained suggested alternariol derivatives may serve as naturally occurring potent anti-inflammatory candidates. This study opens new avenues for the design and development of innovative anti-inflammatory drugs that specifically target INF-γ, IL-1ß and INF-γ.

Micro/Nanostructured Bioactive Titanium Implant Surface with Sol-Gel Silicate Glass Nanoparticles.

PURPOSE: To develop a surface coating of sol-gel 70S30C bioactive glass (BAG) nanoparticles on titanium disks and dental implants and characterize the BAG coating from the standpoint of average surface roughness, adhesion strength, and coating stability upon implant insertion under clinical settings. MATERIALS AND METHODS: BAG was prepared using a modified sol-gel technique, then milled into nanoparticles. The resultant powder was characterized in terms of phase structure, composition, and particle size. Titanium disks and dental implants were coated with BAG nanoparticles via electrophoretic deposition. Surface characterization of coated implants was conducted. Uncoated and BAGcoated implants were examined for average surface roughness using a confocal laser scanning microscope. Pull-off tests were conducted to measure the adhesion strength of the BAG coating to the underlying disks. To measure the amount of coating loss and evaluate the effect of insertion on coating thickness, coated implants were inserted under clinical settings into artificial and natural bones. RESULTS: BAG nanoparticles had an amorphous structure with particle sizes < 20 nm in diameter. Electrophoresis resulted in a continuous coating that covered the whole implant surface. Microscopic analysis confirmed the porous nanostructure of the BAG coating, which formed a homogenous surface with microcracks. The BAG coating had a uniform thickness of 35.38 ± 4.67 µm. The average surface roughness was significantly lower for BAG-coated implants, with less surface irregularities (3.34 ± 0.45 µm for uncoated implants, 1.45 ± 0.23 µm for BAG-coated implants). An adhesion strength of 18.51 ± 3.37 MPa was recorded for the BAG coating. After insertion into artificial bone, 66.23 ± 10.23% of the coating weight remained on the implant surface. A reduction in the thickness of the BAG coating only occurred in sites of high friction with bone after implant insertion into bovine bone. CONCLUSIONS: Coating titanium implants with 70S30C BAG nanoparticles is attainable through electrophoretic deposition and results in a homogenous coating layer with a moderately rough surface, considerable adhesion strength, and high coating stability during implant insertion. Int J Oral Maxillofac Implants 2023;38:591-606. doi: 10.11607/jomi.10272.

New complementary python codes to locate Single Nucleotide Polymorphisms (SNPs) and Overlapping G-Quadruplex Sequences (G4s).

G-quadruplexes (G4s) are non-canonical DNA and RNA secondary structures that control gene regulation. A single nucleotide polymorphism (SNP) is a small genetic variation occurring within a DNA sequence and accounting for the variabilities between individuals. While the majority of SNPs, especially those frequent in the population, are considered as benign genetic variations, few others can lead to diseases. SNPs occurring in G4 sequences were reported to modulate gene regulation. In order to find overlaps between predicted G4 sequences and SNPs located in the genomic regions, we developed two complementary computational python codes (SNP-locator and G4-overlap). The codes map a mutation to the overlapping/closest G4 sequences, based on the genetic variant name and the FASTA format of the corresponding gene. We validated these two codes on a set of 31 SNP variants occurring in cytochromes P450 genes and podocytes-marker genes. Out of 31 SNPs, 28 were accurately located using the mentioned codes.•SNP-locator code locates any SNP in promoters, upstream regulatory regions, exons and introns.•The SNP-locator code requires the FASTA genomic sequence of the studied gene and the genetic variant nomenclature at the cDNA level.•G4-overlap code maps the SNP to the overlapping or the closest G4 sequence.

PGC-1α induced mitochondrial biogenesis in stromal cells underpins mitochondrial transfer to melanoma.

INTRODUCTION: Progress in the knowledge of metabolic interactions between cancer and its microenvironment is ongoing and may lead to novel therapeutic approaches. Until recently, melanoma was considered a glycolytic tumour due to mutations in mitochondrial-DNA, however, these malignant cells can regain OXPHOS capacity via the transfer of mitochondrial-DNA, a process that supports their proliferation in-vitro and in-vivo. Here we study how melanoma cells acquire mitochondria and how this process is facilitated from the tumour microenvironment. METHODS: Primary melanoma cells, and MSCs derived from patients were obtained. Genes' expression and DNA quantification was analysed using Real-time PCR. MSC migration, melanoma proliferation and tumour volume, in a xenograft subcutaneous mouse model, were monitored through bioluminescent live animal imaging. RESULTS: Human melanoma cells attract bone marrow-derived stromal cells (MSCs) to the primary tumour site where they stimulate mitochondrial biogenesis in the MSCs through upregulation of PGC1a. Mitochondria are transferred to the melanoma cells via direct contact with the MSCs. Moreover, inhibition of MSC-derived PGC1a was able to prevent mitochondrial transfer and improve NSG melanoma mouse tumour burden. CONCLUSION: MSC mitochondrial biogenesis stimulated by melanoma cells is prerequisite for mitochondrial transfer and subsequent tumour growth, where targeting this pathway may provide an effective novel therapeutic approach in melanoma.

Evolution of gastroesophageal reflux disease symptoms after bariatric surgery: A dose-response meta-analysis.

BACKGROUND: Obesity is associated with increased prevalence of gastroesophageal reflux disease, with recent reports suggesting improvement in gastroesophageal reflux disease symptoms and weight loss following bariatric surgical intervention. However, the exact impact of the type of bariatric surgery on the evolution of gastroesophageal reflux disease symptoms has remained unexamined. METHODS: We systematically searched electronic databases (PubMed, EMBASE, Web of Science, and the Cochrane Library from inception to December 2018) for eligible studies that satisfy prespecified inclusion criteria. We included clinical trials of all designs that reported on gastroesophageal reflux disease outcomes following laparoscopic sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass. Two independent reviewers extracted relevant data based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Data were pooled using a random-effects model. Main outcomes were symptomatic improvement in gastroesophageal reflux disease symptoms following bariatric surgery. RESULTS: A total of 31 studies were analyzed, and a robust-error meta-regression model was used to conduct a dose-response meta-analysis synthesizing data on 31 studies that reported gastroesophageal reflux disease outcomes after bariatric surgery. Of 5,295 patients who underwent either laparoscopic sleeve gastrectomy (n = 4,715 patients) or laparoscopic Roux-en-Y gastric bypass (n = 580 patients), 63.4% experienced improvement in gastroesophageal reflux disease symptoms (95% CI 32.46-72.18). The dose-response meta-analysis demonstrated a window period of 2 years for sustained improvement after which symptoms began to recur in those that were asymptomatic. CONCLUSION: Bariatric surgery may improve gastroesophageal reflux disease symptoms in obese patients who underwent laparoscopic sleeve gastrectomy; however, the most favorable effect is likely to be found after Roux-en-Y gastric bypass surgery. The effects were not sustained and returned to baseline within 4 years.

Blood Demand and Challenges for Patients With Beta-Thalassemia Major in Eastern Saudi Arabia.

Background ß-thalassemia major is a hereditary disorder of hemoglobin (Hb) that results in defective Hb synthesis, leading to severe chronic anemia. The mainstay of its treatment is lifelong regular packed red cell transfusions associated with iron-chelating therapy. Globally, there is a gap between blood donation and the actual needs of the patients who depend on transfusion. Patients with ß-thalassemia major are no exception and have limited access to regular and safe blood transfusions. This study aimed to assess the gap between the demand and supply of blood for transfusion-dependent patients with ß-thalassemia major treated at the Hereditary Blood Diseases Center, Al Ahsa, Eastern Saudi Arabia. Methodology This was a retrospective, cross-sectional study conducted at the Hereditary Blood Disease Center, Al Ahsa, Saudi Arabia, including patient data from January 2017 to December 2019. We used Excel 365 from Microsoft Office 2016, version 1706. Results A total of 158 patients were on chronic transfusion. Of the total patients, 65% were adults, while the remaining 35% comprised the pediatric population. The total number of units requested and received during the three-year period was 14,509 and 9,530, respectively, indicating a gap of 4,979 (34%) units. The age of most of the units received was more than 14 days: 36% of those in 2017, 49.9% in 2018, and 61.5% in 2019. Rare blood groups and alloimmunization accounted for <8% of the patients. Prestorage filtration was the policy for all units. Conclusions There was a gap between the demand and supply of blood for patients with ß-thalassemia major treated at our center. We suggest raising awareness regarding the high demands for fresh red blood cell components in patients with thalassemia major, encouraging voluntary blood donations, enhancing national blood-banking policies, and reducing the fragmentation of blood services to reduce the gap between demand and supply.

External Validation and Recalibration of the CURB-65 and PSI for Predicting 30-Day Mortality and Critical Care Intervention in Multiethnic Patients with COVID-19.

OBJECTIVES: To validate and recalibrate the CURB-65 and pneumonia severity index (PSI) in predicting 30-day mortality and critical care intervention (CCI) in a multiethnic population with COVID-19, along with evaluating both models in predicting CCI. METHODS: Retrospective data was collected for 1181 patients admitted to the largest hospital in Qatar with COVID-19 pneumonia. The area under the curve (AUC), calibration curves, and other metrics were bootstrapped to examine the performance of the models. Variables constituting the CURB-65 and PSI scores underwent further analysis using the Least Absolute Shrinkage and Selection Operator (LASSO) along with logistic regression to develop a model predicting CCI. Complex machine learning models were built for comparative analysis. RESULTS: The PSI performed better than CURB-65 in predicting 30-day mortality (AUC 0.83, 0.78 respectively), while CURB-65 outperformed PSI in predicting CCI (AUC 0.78, 0.70 respectively). The modified PSI/CURB-65 model (respiratory rate, oxygen saturation, hematocrit, age, sodium, and glucose) predicting CCI had excellent accuracy (AUC 0.823) and good calibration. CONCLUSIONS: Our study recalibrated, externally validated the PSI and CURB-65 for predicting 30-day mortality and CCI, and developed a model for predicting CCI. Our tool can potentially guide clinicians in Qatar to stratify patients with COVID-19 pneumonia.

Production, characterization and bio-emulsifying application of exopolysaccharides from Rhodotorula mucilaginosa YMM19.

Microbial exopolysaccharides (EPS) are high molecular weight polymers having different sugar residues. EPS have potential applications in different fields, such as medicine, food and environment. Therefore, there is a growing interest in production, characterization and application of EPS from different microorganisms. The present study designed to investigate the production and characterization of EPS from Rhodotorula mucilaginosa YMM19 isolated from Morus nigra L. fruits as well as to examine their potential emulsifying properties. Effect of NaCl concentration, incubation period and pH on the production of EPS was studied. The maximum EPS production by yeast was achieved at 10% NaCl (9741.84 mg/l). The best incubation time for production of EPS was 5 days. Production of EPS decreased under neutral condition and increased at acidic and alkaline condition. The structural feature of EPS was examined by FT-IR and NMR spectral analysis and confirmed the presence of glucose, glucopyranose and galactose. The isolated EPS showed higher emulsification capacity with emulsification activity of 71% and emulsifying index of 60%. The EPS gave strong emulsification for farnesol and was more effective than sodium dodecyl sulphate, a reference emulsifier, in enhancing the herbicidal activity of farnesol against Melilotus indicus under greenhouse condition. The results suggest that the EPS produced by YMM19 strain has a potential to be used as emulsifying agent in pesticide formulations.

Antibacterial and herbicidal properties of secondary metabolites from fungi.

Twenty-eight compounds were isolated from endophytic, soil and marine fungi and their structures were elucidated through spectroscopic methods. The isolated compounds were tested for their antibacterial and herbicidal activities against phytopathogenic bacteria and barnyard grass weed for the first time. Methyleurotinone (14) was the most potent compound against Pectobacterium carotovorum subsp. carotovorum, Pseudomonas syringae pv. syringae, Rhizobium radiobacter and Ralstonia solanacearum with minimum inhibitory concentration (MIC) values of 31.3, 125, 31.3 and 125 mg/L, respectively. Compounds 13-15 were highly effective in reducing the development of potato tuber soft rot disease caused by P. carotovorum subsp. carotovorum. Furthermore, twelve of the tested compounds induced a significant reduction in seed germination of Echinochloa crus-galli at 2 mM with compounds 8 and 26 causing complete inhibition of seed germination. Also, compounds 4, 22, 5, 8, 18 and 25-27 induced remarkable reduction of root and shoot growth of E. crus-galli at 2 mM.

Dual-binding conjugates of diaromatic guanidines and porphyrins for recognition of G-quadruplexes.

The first conceptualised class of dual-binding guanine quadruplex binders has been designed, synthesised and biophysically studied. These compounds combine diaromatic guanidinium systems and neutral tetra-phenylporphyrins (classical binding moiety for guanine quadruplexes) by means of a semi-rigid linker. An extensive screening of a variety of guanine quadruplex structures and double stranded DNA via UV-vis, FRET and CD experiments revealed the preference of the conjugates towards guanine quadruplexes. Additionally, docking studies indicate the potential dual mode of binding.

Isolation and Identification of Plant Growth-Promoting Bacteria Highly Effective in Suppressing Root Rot in Fava Beans.

In this study, 18 plant growth-promoting bacterial (PGPB) strains were isolated from the rhizosphere of both Red silk-cotton tree (Bombax malabaricum) and Chinese banyan (Ficus retusa). Culture morphology was observed and genotypic characterization was accomplished by sequencing partial 16S rRNA gene. Plant growth promotion traits and antagonistic activities of the strains against phytopathogenic fungi were evaluated. Among all strains, Bacillus thuringiensis (MN419208) exert the highest indole acetic acid (38 µg/ml), produced exopolysaccharides (587.2 µg/ml), and fixed nitrogen which in turn increased both fresh and dry weights of bean plants by 41.5% and 18.8%, respectively. In another greenhouse experiment studying the antifungal activities of seven strains and their co-culture against Rhizoctonia solani (LN735538), B. sonorensis MN419205, B. wiedmannii MN419207, B. subtilis MN419218, and the mixture of (MN419207) and (MN419208) reduced total damping off from 81.7% in control to 30%, 35%, 35%, and 38.3%, respectively, and reduced disease severity index from 33.3% to 20.5%, 22.5%, 14.2%, and 19.3% as well. Our data indicate that these strains are effective in promoting plant growth and in inhibiting R. solani infection nonetheless field experiments are needed to examine their effectiveness as a viable alternative to chemical fertilizers and conventional pesticides.

Water-pipe smoking and serum testosterone levels in adult males in Qatar.

INTRODUCTION: Water-pipe (WP) smoking is the most common method of tobacco consumption in the Middle-East and is rapidly spreading on a global scale. Although, water-pipe smoking is linked to various diseases, such as emphysema and various types of cancers, its effect on testosterone levels has yet to be investigated. This study explores the effect of water-pipe smoking on serum testosterone levels in males in Qatar. METHODS: In this cross-sectional sample within a cohort study, we retrieved data for a total of 1000 male volunteers from the Qatar BioBank (QBB) project. A self-reported questionnaire was used to determine the water-pipe smoking status of participants. Moreover, participants were stratified based on the frequency of smoking. Total testosterone and sex hormone binding globulin (SHBG) were measured clinically, whereas free testosterone and bioavailable testosterone were calculated using Vermeulen's equation. Hormone values of 541 males (277 water-pipe smokers and 264 non-smokers) were compared using multiple regression analysis based on water-pipe smoking status after adjusting for confounding factors. RESULTS: No statistically significant difference was observed between WP smokers and non-water-pipe smokers in the likelihood of having lower or higher total testosterone, after adjustment for confounding factors. Similar results were found in free testosterone, bioavailable testosterone, and sex hormone binding globulin (all p>0.05). When compared with the reference group, both light and heavy water-pipe smokers had a similar likelihood of circulating low total testosterone levels (OR=0.83, 95% CI: 0.46-1.49; and OR=0.80, 95% CI: 0.43-1.49; respectively). CONCLUSIONS: Our results reveal, for the first time, that there is no significant change in total testosterone, free testosterone, bioavailable testosterone and sex hormone binding globulin in waterpipe smokers compared to non-water-pipe smokers. Therefore, we believe that further studies are needed to confirm the effect of water-pipe smoking on testosterone in different populations.

Bioherbicidal activity of terpenes and phenylpropenes against Echinochloa crus-galli.

This study was undertaken to evaluate the herbicidal activity of twelve natural compounds belonging to monoterpenes, phenylpropenes, and sesquiterpenes against Echinochloa crus-galli under laboratory and glasshouse conditions. Experiments were conducted to determine the impact of different concentrations (0.5, 1, 2, 4 and 8 mM) of these compounds on the seed germination and root and shoot growth of barnyard grass. trans-Cinnamaldehyde, eugenol, and thymol caused the highest impact on barnyard grass reducing its seed germination and shoot growth. p-Cymene (EC50 = 0.22 mM) and trans-cinnamaldehyde (EC50 = 0.34 mM) were the most potent compounds in limiting the root growth of the E. crus-galli. In a post-emergent experiment, thymol, trans-cinnamaldehyde, eugenol, farnesol, and nerolidol significantly reduced the shoot growth, fresh and dry weight of two-leaf stage barnyard grass after 2 days of the foliar treatment with the concentrations of 0.5, 1.0 and 2.0%. These compounds induced severe visible injury symptoms where trans-cinnamaldehyde, eugenol, farnesol and nerolidol showed a complete weed control at 1.0 and 2.0%. These compounds were successfully formulated as emulsifiable concentrates and showed higher herbicidal activities against barnyard grass. Altogether, our data showed that trans-cinnamaldehyde, eugenol, thymol, farnesol, and nerolidol can be developed as novel bioherbicides for managing E. crus-galli.

Mapping and characterization of G-quadruplexes in the genome of the social amoeba Dictyostelium discoideum.

G-quadruplexes (G4) are non-canonical DNA and/or RNA secondary structures formed in guanine-rich regions. Given their over-representation in specific regions in the genome such as promoters and telomeres, they are likely to play important roles in key processes such as transcription, replication or RNA maturation. Putative G4-forming sequences (G4FS) have been reported in humans, yeast, bacteria, viruses and many organisms. Here we present the first mapping of G-quadruplex sequences in Dictyostelium discoideum, the social amoeba. 'Dicty' is an ameboid protozoan with a small (34 Mb) and extremely AT rich genome (78%). As a consequence, very few G4-prone motifs are expected. An in silico analysis of the Dictyostelium genome with the G4Hunter software detected 249-1055 G4-prone motifs, depending on G4Hunter chosen threshold. Interestingly, despite an even lower GC content (as compared to the whole Dicty genome), the density of G4 motifs in Dictyostelium promoters and introns is significantly higher than in the rest of the genome. Fourteen selected sequences located in important genes were characterized by a combination of biophysical and biochemical techniques. Our data show that these sequences form highly stable G4 structures under physiological conditions. Five Dictyostelium genes containing G4-prone motifs in their promoters were studied for the effect of a new G4-binding porphyrin derivative on their expression. Our results demonstrated that the new ligand significantly decreased their expression. Overall, our results constitute the first step to adopt Dictyostelium discoideum as a 'G4-poor' model for studies on G-quadruplexes.

Insecticidal potential and repellent and biochemical effects of phenylpropenes and monoterpenes on the red flour beetle, Tribolium castaneum Herbst.

The main objectives of the present study are to introduce new, ecologically safe, and natural compounds for controlling red flour beetle, Tribolium castaneum, and to understand the possible mode of action of these compounds. Therefore, the insecticidal and repellent activities of two phenylpropenes and six monoterpenes have been evaluated against the adults of T. castaneum. The inhibitory effects of these compounds on the activity of adenosine triphosphatases (ATPases) and acetylcholinesterase (AChE) were also tested. In fumigant toxicity assay, (-)-terpinen-4-ol (LC50 = 20.47 µl/l air) and α-terpinene (LC50 = 23.70 µl/l air) exhibited the highest toxicity without significant differences between them. Moreover, (-)-menthone and p-cymene showed strong toxicity, while (-)-citronellal, trans-cinnamaldehde, and eugenol were not active. In contact toxicity assay, the two phenylpropenes, trans-cinnamaldehde and eugenol, had the highest toxicity with same LC50 value of 0.02 mg/cm2. The monoterpenes and phenylpropenes showed pronounced repellent effect on the adults of T. castaneum at 0.001 mg/cm2 with (-)-menthone, trans-cinnamaldehyde, and α-terpinene being the most effective after 2 h of exposure. Repellent activity depended on compound, exposure time, and concentration. On the other hand, the tested compounds exhibited strong inhibition of ATPases form the larvae of T. castaneum as their IC50 values ranged between 1.74 and 19.99 mM. In addition, (-)-citronellal (IC50 = 9.82 mM) and trans-cinnamaldehde (IC50 = 23.93 mM) caused the highest inhibitory effect on AChE, while α-pinene (IC50 = 53.86) and p-cymene (IC50 = 68.97 mM) showed the weakest inhibitory effect. The results indicated that the tested phenylpropenes and monoterpenes had the potential to be developed as natural insecticides and repellents for controlling T. castaneum.

Defining professionalism for mental health services: a rapid systematic review.

Background: Efforts have been made to define professionalism across the professions, yet little attention has been paid to the concept in mental health services, where patients' needs differ to that in other healthcare specialties. Aims: To derive a definition of professionalism for mental health services using the existing literature. Method: A rapid, systematic review was conducted to identify empirical and non-empirical records that described professionalism in a mental health service context from 2006 to 2017. Studies were synthesised narratively using thematic analysis. Results: Seventy records were included in the review. Professionalism was described on two levels; at a societal level, a dynamic social contract between professions and society, and; at an individual level, having intrapersonal, interpersonal, and working professionalism. Utilising emerging themes, an operationalised definition of professionalism, suitable for a mental health service context was derived. Conclusions: Within mental health services, emphasis is placed on the interpersonal aspects of practice such as communication skills, maintaining boundaries and humanity. Themes relating to the vulnerability of patients and the challenge of supporting autonomy and choice whilst maintaining safety and acting in a client's best interest are also evident. 'Practical wisdom' and a flexible approach to working are needed to manage these challenging situations.

Cicer arietinum extract ameliorate γ-irradiation disorders via modulation of oxidative/antioxidative pathway.

Ionized radiations trigger thoughtful adverse hazards through multiple organ dysfunctions. Recently, antioxidant-based biodrugs are used to prevent and treat ionizing radiation hazards. The present study aimed to investigate the prospective ameliorative effect of Cicer arietinum extract (CAE) against γ-irradiation and the pathway of this amelioration in male albino rats. Twenty four rats were allocated into four groups; (i) control group, (ii) CAE group in which rats treated with a dosage of 500 mg CAE/kg b.wt, (iii) γ-irradiated group in which rats exposed to 6Gy γ-irradiation, (iv) γ-irradiated+CAE group; rats of this group treated with CAE 1 h post exposure. All rats treated for 21 days. Liver, kidney and femoral bone were rapidly excised and homogenized for the biochemical analysis. Energy dispersive X-ray (EDX) and inductively coupled plasma emission spectrometer (ICP) analyses exhibit that γ-irradiation elicits significant change in the essential trace elements content in liver, kidney, and bone. Further, significant increases in TBARS and H2O2 contents accompanied by significant decreases in GSH, SOD, CAT, and GPx activities in liver, kidney and bone tissues were recorded in the γ-irradiated rats compared to control group. Additionally, marked reduction in the thickness of cortical bone was recorded in rats exposed to γ-irradiation. Conversely, CAE (500 mg/kg b.wt, p.o) administration for 21 days to γ-irradiated rats effectively reverses most of the altered parameters of the γ-irradiated rats. In conclusion, the present findings suggested that CAE is a potential agent that can be used against radiation hazards. This effect may be owing to its antioxidant mechanism, as CAE has an inhibitory effect against hydrogen peroxide (H2O2) and superoxide radical (O2·-) beside its ferric reducing antioxidant power (FRAP). This finding recommended that CAE can be utilized clinically to mitigate ionized radiation-induced hazard effects.