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Negative social ties as emerging risk factors for accelerated aging, inflammation, and multimorbidity

Negative social ties, or “hasslers,” are pervasive yet understudied components of social networks that may accelerate biological aging and morbidity. Using ego-centric network data and DNA methylation-based biological aging clocks (i.e., DunedinPACE and age-accelerated GrimAge2) from saliva from a state representative probability sample in Indiana, we examine how negative social ties are associated with accelerated biological aging and a broad range of health outcomes, including inflammation and multimorbidity. Negative relationships are not rare within close relationships, as nearly 30% of individuals report having at least one hassler in their network. These hasslers tend to occupy peripheral network positions and are more likely to be connected through weak, uniplex ties. Importantly, exposure to negative social ties follows patterns of social and health vulnerability, with women, daily smokers, people in poorer health, and those with adverse childhood experiences more likely to report having hasslers in their networks. Having more hasslers is associated with accelerated biological aging in both rate and cumulative burden: Each additional hassler corresponds to approximately 1.5% faster pace of aging and roughly 9 mo older biological age. Moreover, not all hasslers exert the same influence; kin and nonkin hasslers show detrimental associations, whereas spouse hasslers do not. Finally, a greater number of hasslers is associated with multiple adverse health outcomes beyond epigenetic aging. These findings together highlight the critical role of negative social ties in biological aging as chronic stressors and the need for interventions that reduce harmful social exposures to promote healthier aging trajectories.

Within primary breast tumors, a high-risk cell state may seed future metastases

Understanding which cells within a tumor will go on to form metastases remains one of the major challenges in cancer research. A study led by the Cell Plasticity in Development and Disease laboratory, headed by Ángela Nieto at the Institute for Neurosciences (IN), a joint center of the Spanish National Research Council (CSIC) and Miguel Hernández University (UMH) of Elche, offers an unexpected answer: The cells that will give rise to metastases can already be identified within the primary tumor.

The study, published in Nature Communications, combines the analysis of a mouse model of breast cancer with patient data. The results show that, at the invasive front of the tumor, there is a specific population of cells capable of both invading and either proliferating or entering a dormant state. This balance determines whether cells that escape the tumor can initiate new tumor growths in distant organs, the feared metastases.

Nieto’s team has been studying the epithelial-to-mesenchymal transition (EMT) for decades, a program that controls cell migration during embryonic development and is reactivated in tumors to enable cancer cells to spread and form metastases.

Memory T Cells in Respiratory Virus Infections: Protective Potential and Persistent Vulnerabilities

Respiratory virus infections, such as those caused by influenza viruses, respiratory syncytial virus (RSV), and coronaviruses, pose a significant global health burden. While the immune system’s adaptive components, including memory T cells, are critical for recognizing and combating these pathogens, recurrent infections and variable disease outcomes persist. Memory T cells are a key element of long-term immunity, capable of responding swiftly upon re-exposure to pathogens. They play diverse roles, including cross-reactivity to conserved viral epitopes and modulation of inflammatory responses. However, the protective efficacy of these cells is influenced by several factors, including viral evolution, host age, and immune system dynamics.

Gut microbiome is associated with recurrence-free survival in patients with resected high-risk melanoma receiving adjuvant immune checkpoint blockade

Respiratory virus infections, such as those caused by influenza viruses, respiratory syncytial virus (RSV), and coronaviruses, pose a significant global health burden. While the immune system’s adaptive components, including memory T cells, are critical for recognizing and combating these pathogens, recurrent infections and variable disease outcomes persist. Memory T cells are a key element of long-term immunity, capable of responding swiftly upon re-exposure to pathogens. They play diverse roles, including cross-reactivity to conserved viral epitopes and modulation of inflammatory responses. However, the protective efficacy of these cells is influenced by several factors, including viral evolution, host age, and immune system dynamics. This review explores the dichotomy of memory T cells in respiratory virus infections: their potential to confer robust protection and the limitations that allow for breakthrough infections. Understanding the underlying mechanisms governing the formation, maintenance, and functional deployment of memory T cells in respiratory mucosa is critical for improving immunological interventions. We highlight recent advances in vaccine strategies aimed at bolstering T cell-mediated immunity and discuss the challenges posed by viral immune evasion. Addressing these gaps in knowledge is pivotal for designing effective therapeutics and vaccines to mitigate the global burden of respiratory viruses.

Targeting biomolecular condensates: beyond dissolution

Biomolecular condensates control key cellular processes, from gene expression to signal transduction, by organizing molecules through selective compartmentalization. Increasing evidence links their dysregulation to cancer, neurodegeneration, and other diseases, positioning condensates as promising therapeutic targets. This review explores emerging strategies that go beyond dissolving pathological condensates, including approaches that induce, redirect, or reprogram their dynamics, composition, and physical state. Rather than inhibiting individual proteins, these interventions reshape the cellular organization itself. By targeting the material and functional properties of condensates, such strategies offer a new conceptual framework for therapeutic design in complex, dysregulated biological systems.

Local cues, local killers: human natural killer cells across tissues

Human natural killer cells across tissues.

Natural killer cells residing in tissues are distinct compared to those in the bloodstream, and their diversity is likely shaped by the microenvironment of individual tissues.

In tissues, natural killer cells are exposed to an environment with low oxygen levels, a distinct cytokine milieu, and different neighboring cells compared to their circulating counterparts, leading to a unique metabolic and functional profile.

Tissue-resident natural killer cells in most human tissues appear to be only transiently tissue-resident and recirculate via the lymphatic system back to the bloodstream. Lymphatic vessels and lymph nodes contain various natural killer cell populations of distinct origins. Tumor responses of tissue-resident natural killer cells depend on the tissue niche and tumor microenvironment context, with tissue-resident natural killer cells having a more immunoregulatory rather than a direct cytotoxic role during tumorigenesis. sciencenewshighlights ScienceMission https://sciencemission.com/natural-killer-cells


Natural killer (NK) cells are part of the innate immune system and reside in multiple tissues. During steady-state conditions, they contribute to tissue homeostasis, while in disease settings, tissue-resident (tr) NK cells are positioned at the frontline of immune surveillance. Due to their exposure to local microenvironments, NK cells residing outside the bloodstream exhibit phenotypic, transcriptional, functional, and metabolic features that distinguish them from their circulating counterparts. In this review, we outline the defining characteristics of tr NK cells, discuss their recirculation potential, and summarize their functional and metabolic specialization across human tissues. Finally, using cancer as an example, we highlight how tr NK cells are altered in disease and how local tissue environments shape their functional states.

B cell deficiency limits exercise capacity by remodeling liver glutamate metabolism

Now online! B cells regulate exercise capacity through immune-independent liver-muscle metabolic signaling, and B cell deficiency limits muscle performance. Mechanistically, B cell-secreted TGF-β1 increases hepatic glutamine-to-glutamate conversion, raising glutamate in blood and muscle. This promotes muscle calcium signaling and mitochondrial function, positively regulating exercise capacity.

#Polymath

This is one of my favourite comparisons: polymathy is cognitive biodiversity.

Monoculture farming depletes soil, invites disease, collapses under pressure. One blight, one drought and the whole field dies.

Why do we accept the same fragility in how we think?

The specialist mind is similar to a monoculture. Trained to the depth in one domain and optimized for known conditions. When the paradigm breaks, it can only do what it has always done.

Physicists Propose a New Kind of Laser That Would Fire Neutrinos

Physicists have proposed a new way to make neutrinos at accelerated rates. This method would use a state of matter close to absolute zero called a Bose-Einstein condensate. It would harness quantum effects that can produce neutrinos faster than ordinary radioactive decays. This tool would produce a large and controllable beam of neutrinos. They could have similar properties to photons (particles of light) in an optical laser.

Neutrinos are fundamental particles that interact extremely weakly with matter. It is very difficult to produce and detect neutrinos. It requires large detectors and powerful sources such as nuclear reactors or particle accelerators. A controllable, coherent source of neutrinos on a bench-top scale would have a significant impact on neutrino research. This type of technology would provide new opportunities to understand their interactions and quantum mechanical properties. In addition, the specific radioactive decays that would enable such a controllable, coherent neutrino source on a small scale could lead to new applications. These applications could include production of rare isotopes for medical physics and neutrino-based communication.

Lasers have been revolutionary in enabling the development of many aspects of modern science and technology. They are based on the amplification of light via stimulated emission. This is a quantum mechanical process whereby an excited atom is forced to emit a second photon upon absorption of another with the same wavelength. Due to their tiny masses, neutrinos behave similarly to photons in many situations. However, they cannot be used for lasing because their fermionic nature inhibits stimulated emission. For this reason, it is not possible to develop a neutrino laser using this traditional mechanism.

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