Two Forms of Sexual Dimorphism in Gene Expression in Drosophila melanogaster: Their Coincidence and Evolutionary Genetics.

Phenotypic sexual dimorphism can be mediated by sex differences in gene expression. We examine two forms of sexual dimorphism in gene expression in Drosophila melanogaster: 1) sex-biased gene expression (SBGE) in which the sexes differ in the amount a gene is expressed and 2) sexual dimorphism in isoform usage, that is, sex-specific splicing (SSS). In whole body (but not the head) expression, we find a negative association between SBGE and SSS, possibly suggesting that these are alternate routes to resolving sexual antagonistic selection. Next, we evaluate whether expression dimorphism contributes to the heterogeneity among genes in rmf, the intersexual genetic correlation in body expression that constrains the extent to which a gene's expression can evolve independently between the sexes. We find lower rmf values for genes with than without SSS. We find higher rmf values for male- than female-biased genes (except genes with extreme male bias), even though male-biased genes are known to have greater evolutionary divergence in expression. Finally, we examine population genetic patterns in relation to SBGE and SSS because genes with expression dimorphism have likely experienced a history of sex differences in selection. SSS is associated with reduced values of Tajima's D and elevated direction of selection (DoS) values, suggestive of higher rates of adaptive evolution. Though DoS is highly elevated for genes with extreme male bias, DoS otherwise tends to decline from female-biased to unbiased to male-biased genes. Collectively, the results indicate that SBGE and SSS are differentially distributed across the genome and are associated with different forms of selection.

Iridium(III)-catalyzed ß-trifluoromethyl enone carbonyl-directed regioselective ortho-C(sp2)-H olefination.

Due to the lower LUMO energy level at the ß-position of α,ß-unsaturated-ß-trifluoromethyl enone than that of its non-fluorinated counterpart, there is a challenge to activate the sp2 C-H bond of aromatic rings. Herein, we have reported iridium(III)-catalyzed ß-trifluoromethyl enone carbonyl-directed regioselective aromatic C(sp2)-H olefination with acrylates under oxidative conditions. Furthermore, coupling with natural product-derived acrylates, scale-up and product diversification have also been performed.

Metal nanoparticles to improve the heat resilience in wheat (Triticum aestivumL.).

This study evaluated the efficacy of phytogenic silver and zinc nanoparticles in improving heat resilience in various wheat varieties. The silver and zinc nanoparticles were synthesized using plant leaf extract and characterized using various techniques. Four wheat varieties (DBW187, Black Wheat, DBW 50, and PBW 621) were subjected to field trials. The random block design was used, and nanoparticles in different concentrations were applied at various growth stages and morphologically, and yield parameters were recorded. UV-vis spectroscopy spectral analysis showed peaks for Ag nanoparticles at 420 nm wavelength and Zn nanoparticles at 240 and 350 nm wavelength, depicting the preliminary confirmation of nanoparticle synthesis. Electron microscopic analysis (TEM and SEM) provided morphological insights and confirmed synthesis of fine-sized particle mostly in a range between 10 and 60 nm. Energy dispersive x-ray analysis confirmed the elemental composition of the synthesized nanoparticles, with Ag and Zn elements detected in their respective samples. It also confirmed the oxide nature of synthesized ZnNPs. Dynamic light scattering analysis provided size distribution profiles, indicating average sizes of approximately 61.8 nm for Ag nanoparticles and 46.5 nm for Zn nanoparticles. The concentrations of Ag and Zn nanoparticles in the samples were found to be 196.3 ppm and 115.14 ppm, respectively, through atomic absorption spectroscopic analysis. Fourier transform infrared spectroscopy analysis revealed characteristic functional groups present in the nanoparticles. The results of field experiments established that Ag nanoparticles at 75 ppm concentration exhibited the most significant enhancements in plant growth. Conversely, Zn nanoparticles at a 100 ppm concentration demonstrated the most substantial improvements in the growth and yield of heat-stressed wheat varieties. The study concludes that optimized concentrations of silver and zinc nanoparticles can effectively improve heat stress resilience in wheat. These findings are promising to enhance abiotic stress resilience in crops.

Catalytic and Chemodivergent Synthesis of 1-Substituted 9H-Pyrrolo[1,2-a]indoles via Annulation of ß-CF3 Enones with 3-Substituted Indoles.

Chemodivergent reactions are more advantageous in organic synthesis that yield diversely functionalized scaffolds from common starting materials. Herein, we report an efficient metal-free chemodivergent protocol for the synthesis of 1-substituted 9H-pyrrolo[1,2-a]indole derivatives in the presence of catalytic amounts of Lewis acid/Brønsted acid conditions using 3-substituted indoles and ß-trifluoromethyl-α,ß-unsaturated ketones. Fine-tuning of the catalyst and solvent system in the reaction conditions deliver the trifluoromethyl, trifluoroethylcarboxylate, or carboxylic acid substituents on the C1-position of 9H-pyrrolo[1,2-a]indole derivatives in situ. It is postulated that the solvent and LA/BA catalyst interaction was found to be crucial for the catalytic C-F activation in these transformations.

Pyridine C(sp2)-H bond functionalization under transition-metal and rare earth metal catalysis.

Pyridine is a crucial heterocyclic scaffold that is widely found in organic chemistry, medicines, natural products, and functional materials. In spite of the discovery of several methods for the synthesis of functionalized pyridines or their integration into an organic molecule, new methodologies for the direct functionalization of pyridine scaffolds have been developed during the past two decades. In addition, transition-metal-catalyzed C-H functionalization and rare earth metal-catalyzed reactions have flourished over the past two decades in the development of functionalized organic molecules of concern. In this review, we discuss recent achievements in the transition-metal and rare earth metal-catalyzed C-H bond functionalization of pyridine and look into the mechanisms involved.

Sex-Specific Variance in Fitness and the Efficacy of Selection.

AbstractVariance in fitness is thought to be greater in males than in females in many species. If this is so, there are two potentially contradictory consequences on the efficacy of selection (Nes): greater variance in fitness may allow stronger selection (i.e., increased s), but it will also cause stronger genetic drift (i.e., reduced Ne). We develop a simple model to ask how the stronger condition dependency of fitness in males than in females affects selection and fitness variance in each sex to examine the net effect on the efficacy of selection. We measured the phenotypic variance in fitness for each sex in Drosophila melanogaster in different environmental and mating contexts. Variance in fitness was only approximately one and a half to two times higher in males than in females; juvenile mortality likely dampens the difference in variation between the sexes. Combining these results with previous studies of sex-specific selection on mutations, we infer that the increased drift due to males counterbalances the stronger selection on males in this species, leaving Nes similar to what would be expected if both sexes were "female-like" with respect to selection and variance in fitness. Reasons why this could differ in other species are discussed.

Evaluation of efficacy of Phyto-synthesized iron oxide nanoparticles in contributing drought resilience in wheat (Triticum aestivumL.).

Wheat is the majorly cultivated staple crop worldwide. The world witnesses a great percentage of yield loss of wheat due to drought stress. The present study aimed at evaluating the efficacy of phytosynthesized iron oxide nanoparticles (FeONPs) in contributing to drought resilience in wheat (Triticum aestivumL.) under rain-fed conditions. FeONPs were biosynthesized by using leaf extract ofProsopis cinerariaas a reducing and capping agent. The synthesized nanoparticles were characterized to evaluate the structural and biochemical aspects. The FeONPs were found to be irregularly spherical in shape with a mean size of 42.6 nm. The concentration of nanoparticles in the sample was found to be 164.01 mg l-1. An experimental setup was laid out in a randomized-plot design with 3 replications for Rabi season 2020-2021. Five dosages of nanoparticles were prepared as 12.5, 25, 50, 75 and 100 ppm from the stock solution. The wheat crop varieties grown in the field were subjected to a total of 3 treatments; Nanopriming, foliar application of FeONPs at seedling development stage (20 DAS), and tillering stage (30 DAS). Plants that were not treated with NPs were considered as control. No irrigation regime was followed as the effect of NPs on the crop was to be assessed under rain-fed conditions only. Plant growth parameters were recorded. The obtained results revealed that the application of FeONPs positively affected all the morphological and yield attributes in the wheat crop. The highest concentrations used were found to be most effective and showed a significantly pronounced effect as compared to the control atp≤ 0.05. The study concluded that the FeONPs can contribute to drought resilience in wheat.

A Comprehensive Review on Critical Issues and Possible Solutions of Motor Imagery Based Electroencephalography Brain-Computer Interface.

Motor imagery (MI) based brain-computer interface (BCI) aims to provide a means of communication through the utilization of neural activity generated due to kinesthetic imagination of limbs. Every year, a significant number of publications that are related to new improvements, challenges, and breakthrough in MI-BCI are made. This paper provides a comprehensive review of the electroencephalogram (EEG) based MI-BCI system. It describes the current state of the art in different stages of the MI-BCI (data acquisition, MI training, preprocessing, feature extraction, channel and feature selection, and classification) pipeline. Although MI-BCI research has been going for many years, this technology is mostly confined to controlled lab environments. We discuss recent developments and critical algorithmic issues in MI-based BCI for commercial deployment.

Patients with a fast progression profile in geographic atrophy have increased CD200 expression on circulating monocytes.

IMPORTANCE: Geographic atrophy (GA) is a progressing atrophy of the neuroretina with no treatment option. BACKGROUND: Age-related malfunction of retinal microglia amplifies response towards age-related tissue stress in age-related macular degeneration. Here, we investigated monocyte CD200 expression - the circulating middleman negotiating retinal microglial activity - in a poorly understood subtype of age-related macular degeneration. DESIGN: Prospective case-control study. PARTICIPANTS: Forty-six patients with GA and 26 healthy controls were included. METHODS: All participants were subjected to a structured interview and detailed retinal examination. Controls were recruited from patient's spouses accompanying them in the clinic to match the groups best possibly. Participants had no history of immune disorders or cancer, and did not receive any immune-modulating medication. Patients did not have any history or sign of choroidal neovascularization in either eye. Fresh drawn blood was stained with monoclonal antibodies and prepared for flow cytometry to evaluate CD200 expression in monocytes and their functional subsets. MAIN OUTCOME MEASURES: The percentage of CD200+ monocytes in patients and controls. RESULTS: We found that monocytes were more CD200 positive in patients with GA compared to healthy age-matched controls. Then, we explored the potential relationship between CD200 expression and important fundus autofluorescence patterns that predict disease progression. Patients with a high risk of progression (patients with high degree of hyperautofluorescence) had distinctly increased CD200 expression compared to other patients with GA. CONCLUSIONS AND RELEVANCE: Our data reveals that abnormal monocytic CD200 expression is present in GA, and in particular among those identified as fast progressors.

Reduce Calibration Time in Motor Imagery Using Spatially Regularized Symmetric Positives-Definite Matrices Based Classification.

Electroencephalogram (EEG) based motor imagery brain⁻computer interface (BCI) requires large number of subject specific training trials to calibrate the system for a new subject. This results in long calibration time that limits the BCI usage in practice. One major challenge in the development of a brain⁻computer interface is to reduce calibration time or completely eliminate it. To address this problem, existing approaches use covariance matrices of electroencephalography (EEG) trials as descriptors for decoding BCI but do not consider the geometry of the covariance matrices, which lies in the space of Symmetric Positive Definite (SPD) matrices. This inevitably limits their performance. We focus on reducing calibration time by introducing SPD based classification approach. However, SPD-based classification has limited applicability in small training sets because the dimensionality of covariance matrices is large in proportion to the number of trials. To overcome this drawback, our paper proposes a new framework that transforms SPD matrices in lower dimension through spatial filter regularized by prior information of EEG channels. The efficacy of the proposed approach was validated on the small sample scenario through Dataset IVa from BCI Competition III. The proposed approach achieved mean accuracy of 86.13 % and mean kappa of 0.72 on Dataset IVa. The proposed method outperformed other approaches in existing studies on Dataset IVa. Finally, to ensure the robustness of the proposed method, we evaluated it on Dataset IIIa from BCI Competition III and Dataset IIa from BCI Competition IV. The proposed method achieved mean accuracy 92.22 % and 81.21 % on Dataset IIIa and Dataset IIa, respectively.

Vertebral Fractures in Duchenne Muscular Dystrophy Patients Managed With Deflazacort.

BACKGROUND: Corticosteroids are widely used in the management of patients with Duchenne muscular dystrophy (DMD). They improve quality of life in these patients by prolonging ambulation and preserving cardiorespiratory status. However, corticosteroid treatment is associated with a decrease in bone mineral density (BMD) and an increased risk of vertebral fractures (VF). The purpose of this study was to investigate the prevalence of VF in patients with DMD undergoing long-term treatment with the corticosteroid deflazacort. METHODS: We retrospectively reviewed 49 male patients with DMD on long-term deflazacort therapy at a single institution. All patients had received deflazacort for at least 2 years. VF prevalence, age at start of deflazacort treatment, duration of treatment, BMD Z-score and patient ambulatory status at the time of fracture were evaluated. RESULTS: Of the 49 patients on long-term deflazacort treatment, 26 had VF. Out of these patients who had VF, 19% showed evidence of VF in their third year of therapy, 50% within 5 years of starting therapy, 69% within 7 years of starting therapy, and 100% within 9 years. The first evidence of VF was observed at mean BMD Z-score, lumbar (L)=-2.2 and whole body (B)=-3.1. Eighty-five percent of these patients had at least 3 collapsed vertebrae. Mean BMD Z-score at the time of or before when multiple fractures were noted was -2.4 (L) and -3.4 (B). Patients who started deflazacort at age 3 to 5, 5 to 7 or 7 to 9 years developed a VF after a mean of 4.7, 5.4, or 5.7 years, respectively. Sixty-two percent of patients had VF by the age of 12 years and 91% of patients by age of 15 years. Twenty-one of 26 patients were ambulatory at the time of VF. CONCLUSIONS: Our findings suggest that there is a high risk of VF associated with length of deflazacort use in DMD patients, regardless of age at start of therapy. LEVEL OF EVIDENCE: Level III-retrospective therapeutic study.

The physical environment mediates male harm and its effect on selection in females.

Recent experiments indicate that male preferential harassment of high-quality females reduces the variance in female fitness, thereby weakening natural selection through females and hampering adaptation and purging. We propose that this phenomenon, which results from a combination of male choice and male-induced harm, should be mediated by the physical environment in which intersexual interactions occur. Using Drosophila melanogaster, we examined intersexual interactions in small and simple (standard fly vials) versus slightly more realistic (small cages with spatial structure) environments. We show that in these more realistic environments, sexual interactions are less frequent, are no longer biased towards high-quality females, and that overall male harm is reduced. Next, we examine the selective advantage of high- over low-quality females while manipulating the opportunity for male choice. Male choice weakens the viability advantage of high-quality females in the simple environment, consistent with previous work, but strengthens selection on females in the more realistic environment. Laboratory studies in simple environments have strongly shaped our understanding of sexual conflict but may provide biased insight. Our results suggest that the physical environment plays a key role in the evolutionary consequences of sexual interactions and ultimately the alignment of natural and sexual selection.

Low-interference washing-free electrochemical immunosensor using glycerol-3-phosphate dehydrogenase as an enzyme label.

In washing-free electrochemical detection, various redox and reactive species cause significant interference. To minimize this interference, we report a washing-free electrochemical immunosensor using flavin adenine dinucleotide (FAD)-dependent glycerol-3-phosphate dehydrogenase (GPDH) and glycerol-3-phosphate (GP) as an enzyme label and its substrate, respectively, because the reaction of FAD-dependent dehydrogenases with dissolved O2 is slow and the level of GP preexisting in blood is low (<0.1 mM). A combination of a low electrocatalytic indium-tin oxide (ITO) electrode and fast electron-mediating Ru(NH3)6(3+) is employed to obtain a high signal-to-background ratio via proximity-dependent electron mediation of Ru(NH3)6(3+) between the ITO electrode and the GPDH label. Electrochemical oxidation of GPDH-generated Ru(NH3)6(2+) is performed at 0.05 V vs Ag/AgCl, at which point the electrochemical interference is very low. When a washing-free immunosensor is applied to cardiac troponin I detection in human serum, the calculated detection limit is approximately 10 pg/mL, indicating that the immunosensor is very sensitive in spite of the use of washing-free detection with a short detection period (10 min for incubation and 100 s for electrochemical measurement). The low-interference washing-free electrochemical immunosensor shows good promise for fast and simple point-of-care testing.

Surgical Dislocation of the Hip for the Treatment of Pre-Arthritic Hip Disease.

The purpose of this study was to report the clinical results of surgical dislocation of the hip in the treatment of pre-arthritic hip disease. Between 2005 and 2010, eighty-two patients (89 hips) underwent a surgical dislocation of the hip at a mean age of 30.5 years (range 14.8-51.7); 10 females and 72 males. At a mean follow-up of 7.1 years (range 5-9.6) clinical function improved significantly. 6 patients were converted to total hip arthroplasty and 3 patients underwent an arthroscopy and an additional three patients had >1mm of joint space narrowing at latest follow-up giving us a 9-year cumulative Kaplan-Meier survivorship of 86.4% (CI, 79% to 94%). Thirty-four patients underwent internal fixation removal at a mean of 12.0 months (range 0.3-40.8 months). Although effective in the treatment of early hip disease, the surgical dislocation approach carries a high re-operation rate for removal of internal fixation; consequently, less invasive approaches should be considered for less complex deformities.

Electroreduction-based electrochemical-enzymatic redox cycling for the detection of cancer antigen 15-3 using graphene oxide-modified indium-tin oxide electrodes.

We compare herein biosensing performance of two electroreduction-based electrochemical-enzymatic (EN) redox-cycling schemes [the redox cycling combined with simultaneous enzymatic amplification (one-enzyme scheme) and the redox cycling combined with preceding enzymatic amplification (two-enzyme scheme)]. To minimize unwanted side reactions in the two-enzyme scheme, ß-galactosidase (Gal) and tyrosinase (Tyr) are selected as an enzyme label and a redox enzyme, respectively, and Tyr is selected as a redox enzyme label in the one-enzyme scheme. The signal amplification in the one-enzyme scheme consists of (i) enzymatic oxidation of catechol into o-benzoquinone by Tyr and (ii) electroreduction-based EN redox cycling of o-benzoquinone. The signal amplification in the two-enzyme scheme consists of (i) enzymatic conversion of phenyl ß-d-galactopyranoside into phenol by Gal, (ii) enzymatic oxidation of phenol into catechol by Tyr, and (iii) electroreduction-based EN redox cycling of o-benzoquinone including further enzymatic oxidation of catechol to o-benzoquinone by Tyr. Graphene oxide-modified indium-tin oxide (GO/ITO) electrodes, simply prepared by immersing ITO electrodes in a GO-dispersed aqueous solution, are used to obtain better electrocatalytic activities toward o-benzoquinone reduction than bare ITO electrodes. The detection limits for mouse IgG, measured with GO/ITO electrodes, are lower than when measured with bare ITO electrodes. Importantly, the detection of mouse IgG using the two-enzyme scheme allows lower detection limits than that using the one-enzyme scheme, because the former gives higher signal levels at low target concentrations although the former gives lower signal levels at high concentrations. The detection limit for cancer antigen (CA) 15-3, a biomarker of breast cancer, measured using the two-enzyme scheme and GO/ITO electrodes is ca. 0.1 U/mL, indicating that the immunosensor is highly sensitive.

Blood expression levels of chemokine receptor CCR3 and chemokine CCL11 in age-related macular degeneration: a case-control study.

BACKGROUND: Dysregulation of the CCR3/CCL11 pathway has been implicated in the pathogenesis of choroidal neovascularisation, a common feature of late age-related macular degeneration (AMD). The aim of this study was to investigate the expression of CCR3 and its ligand CCL11 in peripheral blood in patients with neovascular AMD. METHODS: Patients with neovascular AMD and healthy controls were included. Blood samples were obtained and prepared for flow cytometry to investigate the expression of CCR3. Levels of CCL11 were measured in plasma using Cytometric Bead Array. Differences between the groups were tested using Kruskal-Wallis test and Mann-Whitney U test. RESULTS: Patients (n = 83) with neovascular AMD and healthy control persons (n = 114) were included in the study. No significant difference in the expression of CCR3 was found on CD9+ granulocytes when comparing patients suffering from neovascular AMD with any of the control groups. We did not find any alteration in CCL11 levels in patients among the age matched groups. There was no correlation between expression of CCR3/CCL11 and clinical response to treatment with anti-vascular endothelial growth factor (VEGF). CONCLUSION: Our results do not suggest a systemic alteration of the CCR3/CCL11 receptor/ligand complex in patients with neovascular AMD.

Charles Bonnet Syndrome Adversely Affects Vision-Related Quality of Life in Patients with Glaucoma.

PURPOSE: To investigate the impact of Charles Bonnet syndrome (CBS) on vision-related quality of life (VRQoL) in patients with glaucoma. DESIGN: Cross-sectional cohort study. PARTICIPANTS: Twenty-four patients with CBS and 42 matched controls without CBS out of 337 patients with open-angle glaucoma (OAG) with visual field (VF) loss. METHODS: A matching technique was used to identify control patients with similar disease stage, best-corrected visual acuity (BCVA) and age to patients with CBS. Patients' VRQoL was determined using the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25). Rasch-calibrated NEI VFQ-25 scores of the CBS group and the control group were compared. Uni- and multivariable regression analysis was used to evaluate the impact of different factors on VRQoL. MAIN OUTCOME MEASURES: Vision-related quality of life in patients with glaucoma with CBS and without CBS. RESULTS: Vision-related quality of life scores were significantly lower in the CBS group than in the control group on both the visual functioning scale with 39 points (95% confidence interval (CI): 30-48) vs. 52 points (95% CI: 46-58) (P = 0.013) and on the socioemotional scale with 45 points (95% CI: 37-53) vs. 58 points (95% CI: 51-65) (P = 0.015). Univariable regression analysis showed that integrated visual field mean deviation (IVF-MD) (r2 = 0.334, P < 0.001), BCVA in the better eye (r2 = 0.117, P = 0.003), and the presence of CBS (r2 = 0.078, P = 0.013) were significantly correlated to VRQoL scores on the visual functioning scale. Integrated visual field mean deviation (r2 = 0.281, P < 0.001), age (r2 = 0.048, P = 0.042), and the presence of CBS (r2 = 0.076, P = 0.015) were significantly correlated to VRQoL scores on the socioemotional scale. Multivariable regression analysis showed that IVF-MD and the presence of CBS accounted for nearly 40% of the VRQoL score on the visual functioning scale (R2 = 0.393, P < 0.001) and for 34% of the VRQoL score on the socioemotional scale (R2 = 0.339, P < 0.001). CONCLUSIONS: Charles Bonnet syndrome had a significant negative association to VRQoL in patients with glaucoma. Presence of CBS should be considered when evaluating VRQoL in patients with glaucoma. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Content quality and reliability of YouTube videos on oral appliance therapy for obstructive sleep apnea: A systematic analysis.

INTRODUCTION: YouTube's popularity as a health information source raises concerns about credibility due to the absence of peer review. Therefore, this study assessed the content quality and reliability of YouTube videos related to oral appliance therapy for obstructive sleep apnea (OSA). METHODS: Videos were systematically searched on August 20, 2023, using terms determined through Google Trends. Videos were included based on predefined criteria and independently assessed by two researchers. Video demographics were extracted. Video quality was evaluated using audio-visual (AV) quality, video information and quality index (VIQI), global quality score (GQS), and reliability using a modified DISCERN tool (mDISCERN). High and low-content videos were defined based on the customized 10-point scoring system. Inter- and intra-examiner reliability of scoring system were calculated. RESULTS: Most videos were educational (46.3%), presented by dental sleep medicine specialists (42.6%), and aimed at laypersons (63%), with the majority originating from the United States (79.6%). The final 54 videos were categorized as high-content (n = 29, 54%) and low-content (n = 25, 46%). High-content videos had more views, comments, and longer video durations (7.07 ± 6.04 min). Significant differences (p < .05) were observed among high and low-content videos in total VIQI, mDISCERN, GQS, and TCS. Moderate correlations were found between GQS and TCS (r = 0.721), mDISCERN and VIQI (r = 0.649), GQS and VIQI (r = 0.601), and AV quality and VIQI (r = 0.531). CONCLUSION: The study highlights variable content quality and reliability of YouTube videos on oral appliance therapy for OSA, emphasizing the need for guidelines to enhance their educational value and deliver reliable, evidence-based information to patients.