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Patients with rheumatoid arthritis (RA) develop features of accelerated ageing, including immunosenescence. These changes include decreased thymic functionality, expansion of late-differentiated effector T cells, increased telomeric attrition, and excessive production of cytokines (senescence-associated secretory phenotype). The progression of RA has been associated with the early development of age-related co-morbidities, including osteoporosis, cardiovascular complications, and cognitive impairment. Here I review data supporting the hypothesis that immune-senescence contributes to the aggravation of both articular and extra-articular manifestations. Of note, poor cognitive functions in RA were associated with senescent CD28- T cells, inflammaging, and autoantibodies against brain antigens. The pathways of immune-to-brain communication are discussed and provide the rationale for the cognitive impairment reported in RA.

Drawn together by a mentoring program and an unusual crow, middle school misfits Salman, Lu, and Blos form a strong friendship despite teasing by fellow students and the maneuverings of fairies Oberon, Titania, and Puck.

CRISPR-Cas gene editing has revolutionized experimental molecular biology over the past decade and holds great promise for the treatment of human genetic diseases. Here we review the development of CRISPR-Cas9/Cas12/Cas13 nucleases, DNA base editors, prime editors, and RNA base editors, focusing on the assessment and improvement of their editing precision and safety, pushing the limit of editing specificity and efficiency. We summarize the capabilities and limitations of each CRISPR tool from DNA editing to RNA editing, and highlight the opportunities for future improvements and applications in basic research, as well as the therapeutic and clinical considerations for their use in patients. CRISPR-Cas tools have shown exceptional promise in genome engineering over the past decade. Here the authors review the development of CRISPR-Cas9/Cas12/Cas13 nucleases, DNA base editors, prime editors, and RNA base editors, as well as their editing precision, off-target effects, and clinical considerations.

The aging immune system (immunosenescence) has been implicated with increased morbidity and mortality in the elderly. Of note, T cell aging and low-grade inflammation (inflammaging) are implicated with several age-related conditions. The expansion of late-differentiated T cells (CD28−), regulatory T cells, increased serum levels of autoantibodies, and pro-inflammatory cytokines were implicated with morbidities during aging. Features of accelerated immunosenescence can be identified in adults with chronic inflammatory conditions, such as rheumatoid arthritis, and are predictive of poor clinical outcomes. Therefore, there is an interplay between immunosenescence and age-related diseases. In this review, we discuss how the aging immune system may contribute to the development and clinical course of age-related diseases such as neurodegenerative diseases, rheumatoid arthritis, cancer, cardiovascular, and metabolic diseases.

Spin caloritronics focuses on the interaction of electron spins with heat currents. This Review describes newly discovered physical effects that have re-invigorated the field by stimulating further research into understanding the fundamentals of spin–phonon interactions, and providing new avenues to explore to improve current thermoelectric technology. Spintronics is about the coupled electron spin and charge transport in condensed-matter structures and devices. The recently invigorated field of spin caloritronics focuses on the interaction of spins with heat currents, motivated by newly discovered physical effects and strategies to improve existing thermoelectric devices. Here we give an overview of our understanding and the experimental state-of-the-art concerning the coupling of spin, charge and heat currents in magnetic thin films and nanostructures. Known phenomena are classified either as independent electron (such as spin-dependent Seebeck) effects in metals that can be understood by a model of two parallel spin-transport channels with different thermoelectric properties, or as collective (such as spin Seebeck) effects, caused by spin waves, that also exist in insulating ferromagnets. The search to find applications — for example heat sensors and waste heat recyclers — is on.

With non-communicable conditions accounting for nearly two-thirds of deaths worldwide, the emergence of chronic diseases as the predominant challenge to global health is undisputed. In the USA, chronic diseases are the main causes of poor health, disability, and death, and account for most of health-care expenditures. The chronic disease burden in the USA largely results from a short list of risk factors—including tobacco use, poor diet and physical inactivity (both strongly associated with obesity), excessive alcohol consumption, uncontrolled high blood pressure, and hyperlipidaemia—that can be effectively addressed for individuals and populations. Increases in the burden of chronic diseases are attributable to incidence and prevalence of leading chronic conditions and risk factors (which occur individually and in combination), and population demographics, including ageing and health disparities. To effectively and equitably address the chronic disease burden, public health and health-care systems need to deploy integrated approaches that bundle strategies and interventions, address many risk factors and conditions simultaneously, create population-wide changes, help the population subgroups most affected, and rely on implementation by many sectors, including public–private partnerships and involvement from all stakeholders. To help to meet the chronic disease burden, the US Centers for Disease Control and Prevention (CDC) uses four cross-cutting strategies: (1) epidemiology and surveillance to monitor trends and inform programmes; (2) environmental approaches that promote health and support healthy behaviours; (3) health system interventions to improve the effective use of clinical and other preventive services; and (4) community resources linked to clinical services that sustain improved management of chronic conditions. Establishment of community conditions to support healthy behaviours and promote effective management of chronic conditions will deliver healthier students to schools, healthier workers to employers and businesses, and a healthier population to the health-care system. Collectively, these four strategies will prevent the occurrence of chronic diseases, foster early detection and slow disease progression in people with chronic conditions, reduce complications, support an improved quality of life, and reduce demand on the health-care system. Of crucial importance, with strengthened collaboration between the public health and health-care sectors, the health-care system better uses prevention and early detection services, and population health is improved and sustained by solidifying collaborations between communities and health-care providers. This collaborative approach will improve health equity by building communities that promote health rather than disease, have more accessible and direct care, and focus the health-care system on improving population health.

A combination of button accordion and bajo sexto, conjunto originated in the Texas-Mexico borderlands as a popular dance music and became a powerful form of regional identity. Today, listeners and musicians around the world have embraced the genre and the work of conjunto masters like Flaco Jiménez and Mingo Saldívar. Erin E. Bauer follows conjunto from its local origins through three processes of globalization--migration via media, hybridization, and appropriation--that boosted the music's reach. As Bauer shows, conjunto's encounter with globalizing forces raises fundamental questions. What is conjunto stylistically and socioculturally? Does context change how we categorize it? Do we consider the music to be conjunto based on its musical characteristics or due to its performance by Jiménez and other regional players? How do similar local genres like Tejano and norteño relate to ideas of categorization? A rare look at a fascinating musical phenomenon, Flaco's Legacy reveals how conjunto came to encompass new people, places, and styles.

Conductivities are key material parameters that govern various types of transport (electronic charge, spin, heat and so on) driven by thermodynamic forces. Magnons, the elementary excitations of the magnetic order, flow under the gradient of a magnon chemical potential 1 – 3 in proportion to a magnon (spin) conductivity. The magnetic insulator yttrium iron garnet is the material of choice for efficient magnon spin transport. Here we report a giant magnon conductivity in thin yttrium iron garnet films with thicknesses down to 3.7 nm when the number of occupied two-dimensional subbands is reduced from a large number to a few, which corresponds to a transition from three-dimensional to two-dimensional magnon transport. We extract a two-dimensional magnon spin conductivity around 1 S at room temperature, comparable to the (electronic) conductivity of the high-mobility two-dimensional electron gas in GaAs quantum wells at millikelvin temperatures 4 . Such high conductivities offer opportunities to develop low-dissipation magnon-based spintronic devices. The authors report the observation of an enhanced magnon conductivity close to the two-dimensional transport regime in ultrathin yttrium iron garnet.

Gene regulatory networks (GRNs) are key determinants of cell function and identity and are dynamically rewired during development and disease. Despite decades of advancement, challenges remain in GRN inference, including dynamic rewiring, causal inference, feedback loop modeling and context specificity. To address these challenges, we develop Dictys, a dynamic GRN inference and analysis method that leverages multiomic single-cell assays of chromatin accessibility and gene expression, context-specific transcription factor footprinting, stochastic process network and efficient probabilistic modeling of single-cell RNA-sequencing read counts. Dictys improves GRN reconstruction accuracy and reproducibility and enables the inference and comparative analysis of context-specific and dynamic GRNs across developmental contexts. Dictys’ network analyses recover unique insights in human blood and mouse skin development with cell-type-specific and dynamic GRNs. Its dynamic network visualizations enable time-resolved discovery and investigation of developmental driver transcription factors and their regulated targets. Dictys is available as a free, open-source and user-friendly Python package. By probabilistic modeling of gene regulation and expression kinetics, Dictys infers dynamic and context-specific gene regulatory networks using single-cell multiomics data.