Hintonvance1550

05). The results suggested that adolescent ever users of nicotine-containing alternative tobacco products were more likely to keep using them than cigarettes, and the richest adolescents were at the highest risks of tobacco use. Diverse tobacco control measures are needed to improve health equity, especially on alternative tobacco products.The juvenile brain presents plasticity. Oligodendrocytes are the myelinating cells of the central nervous system and myelination can be adaptive. Plasticity decreases from juvenile to adulthood. The mechanisms involving oligodendrocytes underlying plasticity are unclear. Here, we show Na+-K+-Cl- co-transporter 1 (NKCC1), highly expressed in the juvenile mouse brain, regulates the oligodendrocyte activity from juvenile to adulthood in mice, as shown by optogenetic manipulation of oligodendrocytes. The reduced neuronal activity in adults was restored by Nkcc1 overexpression in oligodendrocytes. Moreover, in adult mice overexpressing Nkcc1, long-term potentiation and learning were facilitated compared to age-matched controls. VX-11e cell line These findings demonstrate that NKCC1 plays a regulatory role in the age-dependent activity of oligodendrocytes, furthermore inducing activation of NKCC1 in oligodendrocytes can restore neuronal plasticity in the adult mouse brain.The health of communities has been observed to recover at differential rates in the wake of disasters. In the present study, the 5-year trends in poor self-rated health (SRH) in three municipalities of Iwate Prefecture following the 2011 Great East Japan Earthquake and Tsunami were compared. Annual surveys were conducted from 2011 to 2015 in three municipalities (Otsuchi, Rikuzentakata, and Yamada) that were heavily damaged by the tsunami. We tracked the prevalence of poor SRH in 10,052 participants (mean age, 61.0 years; 39.0% men). Trends in the prevalence of poor SRH were analyzed using generalized linear mixed effect models with control for covariates. Immediately after the disaster (2011), all three municipalities reported similar prevalences of poor SRH (around 15%). Among people under the age of 65 years, there was a gradual improvement in health for residents of Rikuzentakata and Yamada, but the prevalence of poor SRH remained persistently high in Otsuchi. Among people over the age of 65 years, the prevalence of poor SRH remained constant in Rikuzentakata and Yamada but increased over a 5-year follow-up period in Otsuchi. The delayed health recovery in Otsuchi may be due to the characteristics of the local health system. link2 Examination of the variations in health recovery may provide clues about the sources of disaster resilience.Plastic (polyethylene) pollution is a severe cause of deterioration of a healthy environment. For example, ingestion of plastics in the animal gut, clogging of water canals and retarded solid waste management. Many conventional methods of polyethylene degradation include UV photooxidation, thermal oxidation, incineration, chemical oxidation and landfill are being practiced. However, these methods are not feasible, costlier and not a complete solution for this global issue. Therefore, plausible, alternative solution for this issue is biodegradation. Microbes such as bacteria, fungi and algae are involved in polyethylene degradation in its natural habitat. Among them, algae were given very less importance. In our present study, a potential microalga, morphologically identified as Uronema africanum Borge, isolated from a waste plastic bag collected from a domestic waste dumping site in a freshwater lake. This microalga was further treated with the LDPE sheet in BBM culture medium. Based on the results obtained from light microscopy, dark field microscopy, GC-MS, FT-IR, SEM and AFM, it was concluded that the microalga has initiated degradation of LDPE sheet within 30 days of incubation. Concurrently, the configuration of corrosions, abrasions, grooves and ridges were found similar with the morphological features of the microalga. For example, the configuration of the radial disc-like attachment structure of the microalga was found corresponding to the abrasions on the surface of LDPE sheet at an average size of 20-30 µm in diameter. Whereas, the configuration of ridges and grooves were found similar with the filamentous nature of the microalga (10-15 µm width). This is a hitherto report on the biodegradation of LDPE sheet by the microalga Uronema africanum Borge.Serial circulating tumor DNA (ctDNA) monitoring is emerging as a non-invasive strategy to predict and monitor immune checkpoint blockade (ICB) therapeutic efficacy across cancer types. Yet, limited data exist to show the relationship between ctDNA dynamics and tumor genome and immune microenvironment in patients receiving ICB. Here, we present an in-depth analysis of clinical, whole-exome, transcriptome, and ctDNA profiles of 73 patients with advanced solid tumors, across 30 cancer types, from a phase II basket clinical trial of pembrolizumab (NCT02644369) and report changes in genomic and immune landscapes (primary outcomes). Patients stratified by ctDNA and tumor burden dynamics correspond with survival and clinical benefit. High mutation burden, high expression of immune signatures, and mutations in BRCA2 are associated with pembrolizumab molecular sensitivity, while abundant copy-number alterations and B2M loss-of-heterozygosity corresponded with resistance. Upon treatment, induction of genes expressed by T cell, B cell, and myeloid cell populations are consistent with sensitivity and resistance. We identified the upregulated expression of PLA2G2D, an immune-regulating phospholipase, as a potential biomarker of adaptive resistance to ICB. Together, these findings provide insights into the diversity of immunogenomic mechanisms that underpin pembrolizumab outcomes.The pathogenesis of kidney stone formation includes multi-step processes involving complex interactions between mineral components and protein matrix. Calcium-binding proteins in kidney stones have great influences on the stone formation. The spatial distributions of these proteins in kidney stones are essential for evaluating the in vivo effects of proteins on the stone formation, although the actual distribution of these proteins is still unclear. We reveal micro-scale distributions of three different proteins, namely osteopontin (OPN), renal prothrombin fragment 1 (RPTF-1), and calgranulin A (Cal-A), in human kidney stones retaining original mineral phases and textures calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD). OPN and RPTF-1 were distributed inside of both COM and COD crystals, whereas Cal-A was distributed outside of crystals. OPN and RPTF-1 showed homogeneous distributions in COM crystals with mosaic texture, and periodically distributions parallel to specific crystal faces in COD crystals. The unique distributions of these proteins enable us to interpret the different in vivo effects of each protein on CaOx crystal growth based on their physico-chemical properties and the complex physical environment changes of each protein. This method will further allow us to elucidate in vivo effects of different proteins on kidney stone formation.The fission of singlet excitons into triplet pairs in organic materials holds great technological promise, but the rational application of this phenomenon is hampered by a lack of understanding of its complex photophysics. Here, we use the controlled introduction of vacancies by means of spacer molecules in tetracene and pentacene thin films as a tuning parameter complementing experimental observables to identify the operating principles of different singlet fission pathways. Time-resolved spectroscopic measurements in combination with microscopic modelling enables us to demonstrate distinct scenarios, resulting from different singlet-to-triplet pair energy alignments. For pentacene, where fission is exothermic, coherent mixing between the photoexcited singlet and triplet-pair states is promoted by vibronic resonances, which drives the fission process with little sensitivity to the vacancy concentration. Such vibronic resonances do not occur for endothermic materials such as tetracene, for which we find fission to be fully incoherent; a process that is shown to slow down with increasing vacancy concentration.Mycobacterium abscessus (MAB) is an emerging pathogen that leads to chronic lung infections. link3 To date, the global population structure of non-cystic fibrosis (CF) MAB and evolutionary patterns of drug resistance emergence have not been investigated. Here we construct a global dataset of 1,279 MAB whole genomes from CF or non-CF patients. We utilize whole genome analysis to assess relatedness, phylogeography, and drug resistance evolution. MAB isolates from CF and non-CF hosts are interspersed throughout the phylogeny, such that the majority of dominant circulating clones include isolates from both populations, indicating that global spread of MAB clones is not sequestered to CF contexts. We identify a large clade of M. abscessus harboring the erm(41) T28C mutation, predicted to confer macrolide susceptibility in this otherwise macrolide-resistant species. Identification of multiple evolutionary events within this clade, consistent with regain of wild type, intrinsic macrolide resistance, underscores the critical importance of macrolides in MAB.Concatenation and communication between chemically distinct chemical reaction networks (CRNs) is an essential principle in biology for controlling dynamics of hierarchical structures. Here, to provide a model system for such biological systems, we demonstrate autonomous lifecycles of DNA nanotubes (DNTs) by two concatenated CRNs using different thermodynamic principles (1) ATP-powered ligation/restriction of DNA components and (2) input strand-mediated DNA strand displacement (DSD) using energy gains provided in DNA toeholds. This allows to achieve hierarchical non-equilibrium systems by concurrent ATP-powered ligation-induced DSD for activating DNT self-assembly and restriction-induced backward DSD reactions for triggering DNT degradation. We introduce indirect and direct activation of DNT self-assemblies, and orthogonal molecular recognition allows ATP-fueled self-sorting of transient multicomponent DNTs. Coupling ATP dissipation to DNA nanostructures via programmable DSD is a generic concept which should be widely applicable to organize other DNA nanostructures, and enable the design of automatons and life-like systems of higher structural complexity.Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young children globally, but little is known about within-host RSV diversity. Here, we characterised within-host RSV populations using deep-sequencing data from 319 nasopharyngeal swabs collected during 2017-2020. RSV-B had lower consensus diversity than RSV-A at the population level, while exhibiting greater within-host diversity. Two RSV-B consensus sequences had an amino acid alteration (K68N) in the fusion (F) protein, which has been associated with reduced susceptibility to nirsevimab (MEDI8897), a novel RSV monoclonal antibody under development. In addition, several minor variants were identified in the antigenic sites of the F protein, one of which may confer resistance to palivizumab, the only licensed RSV monoclonal antibody. The differences in within-host virus populations emphasise the importance of monitoring for vaccine efficacy and may help to explain the different prevalences of monoclonal antibody-escape mutants between the two subgroups.