High interfacial charge separation in visible-light active Z- scheme g-C3N4/MoS2 heterojunction: Mechanism and degradation of sulfasalazine

Examination of highly proficient photoactive materials for the degradation of antibiotics from the aqueous solution is the need of the hour. In the present study, a 2D/2D binary junction GCM, formed between graphitic-carbon nitride (g-C3N4) and molybdenum disulphide (MoS2), was fabricated using facile hydrothermal method and its photo-efficacy was tested for the degradation of sulfasalazine (SUL) from aqueous solution under visible-light irradiation. Morphological analysis indicated the nanosheets arrangement of MoS2 and g-C3N4. The visible-light driven experiments indicated that 97% antibiotic was degraded by GCM-30% within 90 min which was found to be quite high than pristine g-C3N4 and MoS2 at solution pH of 6, GCM-30% dose of 20 mg, and SUL concentration of 20 mgL-1. The degradation performance of GCM-30% was selectively improved due to enhanced visible-light absorption, high charge carrier separation, and high redox ability of the photogenerated charges which was induced by the effective Z-scheme 2D/2D heterojunction formed between g-C3N4 and MoS2. The reactive radicals as determined by the scavenging study were •O2-, and h+. A detailed degradation mechanism of SUL by GCM-30% was also predicted based on the detailed examination of the band gaps of g-C3N4 and MoS2

Decreasing referrals to transient ischemic attack clinics during the COVID-19 outbreak: results from a multi-centre cross-sectional survey

Objective. The COVID-19 pandemic is having major implications for stroke care with a documented significant fall in hospital acute stroke admissions. We investigated whether COVID-19 has resulted in a decreased number of referrals to the Transient Ischemic Attack (TIA) clinics across the North West London region. Setting and Design. All the TIA clinical leads of the North West London region received an invitation by email to participate in an online survey in May 2020. The survey questionnaire aimed to assess the number of patients with suspected TIA consecutively referred to each of the TIA clinics of the North West London region between 1st March to 30th April 2020, the COVID-19 period, and between 1st March to 30th April 2019. Results. We had a response rate of 100%. During the COVID-19 period, the TIA clinics of the North West London region received 440 referrals compared to 616 referrals received between 1st March to 30th April 2019 with a fall in the number of the referrals by 28.6%. In April 2020 compared with April 2019, the number of the referrals declined by 40.1%. Conclusions. This multicentre analysis documented a significant reduction in the number of patients referred with suspected TIA to the specialised rapid access outpatient clinics in the North West London region during the COVID-19 pandemic. Future studies are needed to confirm our findings and to better characterise the incidence of cerebrovascular disease during the COVID-19 pandemic

Interactions between the Nse3 and Nse4 Components of the SMC5-6 Complex Identify Evolutionarily Conserved Interactions between MAGE and EID Families

The SMC5-6 protein complex is involved in the cellular response to DNA damage. It is composed of 6-8 polypeptides, of which Nse1, Nse3 and Nse4 form a tight sub-complex. MAGEG1, the mammalian ortholog of Nse3, is the founding member of the MAGE (melanoma-associated antigen) protein family and Nse4 is related to the EID (E1A-like inhibitor of differentiation) family of transcriptional repressors.Using site-directed mutagenesis, protein-protein interaction analyses and molecular modelling, we have identified a conserved hydrophobic surface on the C-terminal domain of Nse3 that interacts with Nse4 and identified residues in its N-terminal domain that are essential for interaction with Nse1. We show that these interactions are conserved in the human orthologs. Furthermore, interaction of MAGEG1, the mammalian ortholog of Nse3, with NSE4b, one of the mammalian orthologs of Nse4, results in transcriptional co-activation of the nuclear receptor, steroidogenic factor 1 (SF1). In an examination of the evolutionary conservation of the Nse3-Nse4 interactions, we find that several MAGE proteins can interact with at least one of the NSE4/EID proteins.We have found that, despite the evolutionary diversification of the MAGE family, the characteristic hydrophobic surface shared by all MAGE proteins from yeast to humans mediates its binding to NSE4/EID proteins. Our work provides new insights into the interactions, evolution and functions of the enigmatic MAGE proteins

Altered Cortico-Striatal–Thalamic Connectivity in Relation to Spatial Working Memory Capacity in Children with ADHD

Introduction: Attention deficit hyperactivity disorder (ADHD) captures a heterogeneous group of children, who are characterized by a range of cognitive and behavioral symptoms. Previous resting-state functional connectivity MRI (rs-fcMRI) studies have sought to understand the neural correlates of ADHD by comparing connectivity measurements between those with and without the disorder, focusing primarily on cortical–striatal circuits mediated by the thalamus. To integrate the multiple phenotypic features associated with ADHD and help resolve its heterogeneity, it is helpful to determine how specific circuits relate to unique cognitive domains of the ADHD syndrome. Spatial working memory has been proposed as a key mechanism in the pathophysiology of ADHD. Methods: We correlated the rs-fcMRI of five thalamic regions of interest (ROIs) with spatial span working memory scores in a sample of 67 children aged 7–11 years [ADHD and typically developing children (TDC)]. In an independent dataset, we then examined group differences in thalamo-striatal functional connectivity between 70 ADHD and 89 TDC (7–11 years) from the ADHD-200 dataset. Thalamic ROIs were created based on previous methods that utilize known thalamo-cortical loops and rs-fcMRI to identify functional boundaries in the thalamus. Results/Conclusion: Using these thalamic regions, we found atypical rs-fcMRI between specific thalamic groupings with the basal ganglia. To identify the thalamic connections that relate to spatial working memory in ADHD, only connections identified in both the correlational and comparative analyses were considered. Multiple connections between the thalamus and basal ganglia, particularly between medial and anterior dorsal thalamus and the putamen, were related to spatial working memory and also altered in ADHD. These thalamo-striatal disruptions may be one of multiple atypical neural and cognitive mechanisms that relate to the ADHD clinical phenotype

Transformation and gene editing in the bioenergy grass \u3ci\u3eMiscanthus\u3c/i\u3e

Background: Miscanthus, a C4 member of Poaceae, is a promising perennial crop for bioenergy, renewable bioproducts, and carbon sequestration. Species of interest include nothospecies M. x giganteus and its parental species M. sacchariforus and M. sinensis. Use of biotechnology-based procedures to genetically improve Miscanthus, to date, have only included plant transformation procedures for introduction of exogenous genes into the host genome at random, non-targeted sites. Results: We developed gene editing procedures for Miscanthus using CRISPR/Cas9 that enabled the mutation of a specific (targeted) endogenous gene to knock out its function. Classified as paleo-allopolyploids (duplicated ancient Sorghum-like DNA plus chromosome fusion event), design of guide RNAs (gRNAs) for Miscanthus needed to target both homeologs and their alleles to account for functional redundancy. Prior research in Zea mays demonstrated that editing the lemon white1 (lw1) gene, involved in chlorophyll and carotenoid biosynthesis, via CRISPR/Cas9 yielded pale green/yellow, striped or white leaf phenotypes making lw1 a promising target for visual confirmation of editing in other species. Using sequence information from both Miscanthus and sorghum, orthologs of maize lw1 were identified; a multi-step screening approach was used to select three gRNAs that could target homeologs of lw1. Embryogenic calli of M. sacchariforus, M. sinensis and M. x giganteus were transformed via particle bombardment (biolistics) or Agrobacterium tumefaciens introducing the Cas9 gene and three gRNAs to edit lw1. Leaves on edited Miscanthus plants displayed the same phenotypes noted in maize. Sanger sequencing confirmed editing; deletions in lw1 ranged from 1 to 26 bp in length, and one deletion (433 bp) encompassed two target sites. Confocal microscopy verified lack of autofluorescence (chlorophyll) in edited leaves/sectors. Conclusions: We developed procedures for gene editing via CRISPR/Cas9 in Miscanthus and, to the best of our knowledge, are the first to do so. This included five genotypes representing three Miscanthus species. Designed gRNAs targeted all copies of lw1 (homeologous copies and their alleles); results also confirmed lw1 made a goo

Maturing Thalamocortical Functional Connectivity Across Development

Recent years have witnessed a surge of investigations examining functional brain organization using resting-state functional connectivity MRI (rs-fcMRI). To date, this method has been used to examine systems organization in typical and atypical developing populations. While the majority of these investigations have focused on cortical–cortical interactions, cortical–subcortical interactions also mature into adulthood. Innovative work by Zhang et al. (2008) in adults have identified methods that utilize rs-fcMRI and known thalamo-cortical topographic segregation to identify functional boundaries in the thalamus that are remarkably similar to known thalamic nuclear grouping. However, despite thalamic nuclei being well formed early in development, the developmental trajectory of functional thalamo-cortical relations remains unexplored. Thalamic maps generated by rs-fcMRI are based on functional relationships, and should modify with the dynamic thalamo-cortical changes that occur throughout maturation. To examine this possibility, we employed a strategy as previously described by Zhang et al. to a sample of healthy children, adolescents, and adults. We found strengthening functional connectivity of the cortex with dorsal/anterior subdivisions of the thalamus, with greater connectivity observed in adults versus children. Temporal lobe connectivity with ventral/midline/posterior subdivisions of the thalamus weakened with age. Changes in sensory and motor thalamo-cortical interactions were also identified but were limited. These findings are consistent with known anatomical and physiological cortical–subcortical changes over development. The methods and developmental context provided here will be important for understanding how cortical–subcortical interactions relate to models of typically developing behavior and developmental neuropsychiatric disorders

Ablation of IL-33 suppresses Th2 responses but is accompanied by sustained mucus obstruction in the Scnn1b transgenic mouse model

Cystic fibrosis is characterized by dehydration of the airway surface liquid layer with persistent mucus obstruction. Th2 immune responses are often manifested as increased mucous cell density (mucous cell metaplasia) associated with mucus obstruction. IL-33 is a known inducer of Th2 immune responses, but its roles in mucus obstruction and related phenotypes in a cystic fibrosis-like lung disease model (i.e., Scnn1b-Tg-positive [Tg+]) mouse, remain unclear. Accordingly, IL-33 knockout (IL-33KO) Tg+ mice were examined and compared with IL-33 heterozygous (IL-33HET) Tg+ mice. As compared with IL-33HET/Tg+ mice, IL-33KO/Tg+ mice had complete absence of bronchoalveolar lavage fluid eosinophilia, accompanied with significant reduction in bronchoalveolar lavage fluid concentration of IL-5, a cytokine associated with eosinophil differentiation and recruitment, and IL-4, a major Th2 cytokine. As compared with IL-33HET/Tg+ mice, IL-33KO/Tg+ mice had significantly reduced levels of Th2-associated gene signatures (Slc26a4, Clca1, Retnla, and Chi3l4), along with complete loss of intracellular mucopolysaccharide staining in the airway epithelium. As compared with IL-33HET/Tg+ mice, although the IL-33KO/Tg+ mice had significantly reduced levels of MUC5AC protein expression, they showed no reduction in the degree of mucus obstruction, MUC5B protein expression, bacterial burden, and neonatal mortality. Interestingly, the histological features, including subepithelial airway inflammation and alveolar space enlargement, were somewhat exaggerated in IL-33KO/Tg+ mice compared with IL-33HET/Tg+ mice. Taken together, our data indicate that although IL-33 modulates Th2 inflammatory responses and MUC5AC protein production, mucus obstruction is not dependent on IL-33

Noise analysis of the Indian Pulsar Timing Array data release I

The Indian Pulsar Timing Array (InPTA) collaboration has recently made its first official data release (DR1) for a sample of 14 pulsars using 3.5 years of uGMRT observations. We present the results of single-pulsar noise analysis for each of these 14 pulsars using the InPTA DR1. For this purpose, we consider white noise, achromatic red noise, dispersion measure (DM) variations, and scattering variations in our analysis. We apply Bayesian model selection to obtain the preferred noise models among these for each pulsar. For PSR J1600$-$3053, we find no evidence of DM and scattering variations, while for PSR J1909$-$3744, we find no significant scattering variations. Properties vary dramatically among pulsars. For example, we find a strong chromatic noise with chromatic index $\sim$ 2.9 for PSR J1939+2134, indicating the possibility of a scattering index that doesn't agree with that expected for a Kolmogorov scattering medium consistent with similar results for millisecond pulsars in past studies. Despite the relatively short time baseline, the noise models broadly agree with the other PTAs and provide, at the same time, well-constrained DM and scattering variations.Comment: Accepted for publication in PRD, 30 pages, 17 figures, 4 table