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Category: genetics – Page 10

The role of nutrient stress in DNA damage

Nutrient stress in DNA damage.

The dynamic interplay between nutrient stress and DNA damage governs cellular survival through coordinated regulation of genomic integrity and metabolic adaptation. Nutrient deprivation, such as glucose or amino acid limitation, engages nutrient sensors, including AMPK and mTORC1, to rewire energy homeostasis while directly influencing DNA repair via regulating PARP1, BRCA1, and other core repair machinery.

DNA damage-activated kinases (ATM/ ATR) orchestrate metabolic reprogramming to fuel repair processes, enforcing context-dependent cell fate decisions via cell cycle arrest or apoptosis regulation.

Nutrient stress exacerbates genomic instability through depleting antioxidants, such as NADPH or glutathione (GSH), promoting oxidative DNA lesions that overwhelm repair capacity, while defective DNA repair conversely drives metabolic dysregulation in tumors.

In the future, more efficacious tumor therapeutic strategies propose combining targeted nutrient stress with DNA damage repair inhibitors to exploit synthetic lethality. However, clinical translation requires resolving key challenges including tumor heterogeneity in nutrient stress-response pathways and adaptive metabolic plasticity during therapy sciencenewshighlights ScienceMission https://sciencemission.com/nutrient-stress–and-DNA-damage

Cells are constantly exposed to various stresses, including nutrient deprivation and genotoxic stress, which dynamically interact with cellular sensing pathways to influence metabolism, gene expression, and homeostasis. The integration of nutrient-sensing mechanisms and DNA damage response pathways is critical in cancer progression. While individual processes are well-characterized, their cross-regulatory mechanisms are just beginning to emerge. Deciphering the interplay between nutrient stress and DNA damage is crucial for elucidating the mechanisms underlying cellular responses to stress and developing therapeutic strategies for various diseases, including cancer. This review highlights the relationship between nutrient stress and DNA damage, especially its underlying sensing pathway and cell fate determination.

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Assembly and annotation of hexaploid Sesuvium portulacastrum genome reveals insights into ion transport-mediated high-salinity adaptation

Yuan et al. report a high-quality chromosome-scale genome of the hexaploid halophyte Sesuvium portulacastrum. Comparative genomics and transcriptomics provide insights into its salt-adaptation evolution and identify the key salt-tolerant gene SpHAK3, offering genetic resources for improving crop tolerance.

From pathology image to biological discovery: LazySlide uses foundation models to connect tissue images and RNA data

Microscopic images of human tissue are a cornerstone of biomedical research and clinical diagnostics. Yet despite their importance, these images often remain difficult to analyze systematically and to connect with other types of biological data. A new study led by CeMM Principal Investigator André Rendeiro and published in Nature Methods introduces “LazySlide,” an open-source software tool that brings the power of foundation models and aims to democratize digital pathology analysis.

Whether it’s an inflamed artery, a tumor spreading into the lung or subtle damage in an organ, when doctors or researchers want to understand what’s happening inside a tissue, one of the most trusted tools is still the microscope. Today, they have largely gone digital: A single tissue sample can be scanned into a whole-slide image so detailed that one can zoom from a bird’s-eye view of the entire tissue down to individual cells. These images, therefore, contain enormous information about tissues from different scales.

However, these images are huge, complex, and often difficult to analyze in a modern, data-driven way. While genetics and single-cell biology have developed effective ways for sharing and comparing data, digital pathology images are hard to incorporate—stored in proprietary formats, processed with incompatible tools, and hard to connect to molecular information like RNA sequencing. Thus, the valuable resources of digitalized tissue images are largely underutilized in many research and clinical settings.

Locus coeruleus–amygdala circuit disrupts prefrontal control to impair fear extinction

One of the most-viewed PNAS articles in the last week is “Locus coeruleus–amygdala circuit disrupts prefrontal control to impair fear extinction.” Explore the article here: https://ow.ly/yFH250Ywubb.

For more trending articles, visit https://ow.ly/tZsG50Ywubg.

Stress undermines extinction learning and hinders exposure-based clinical therapies for a variety of neuropsychiatric disorders. In both animals and humans, dysfunction in the ventromedial prefrontal cortex (vmPFC) contributes to stress-impaired extinction, but the neural circuit by which stress modulates vmPFC function is not known. We hypothesize that locus coeruleus (LC) norepinephrine undermines extinction learning by recruiting projections from the basolateral amygdala (BLA) to vmPFC. Using a combination of circuit-specific chemogenetics and calcium imaging, we find that activation of LC noradrenergic neurons mimics a behavioral stressor (footshock), induces freezing behavior, reduces spontaneous neuronal activity in the vmPFC, impairs extinction learning, and alters the population dynamics of vmPFC ensembles.

Survey: What are neuroscience’s most transformative new tools?

A nicely organized list of what various investigators highlight as the most transformative neuroscience tools from the past 5 years!

Which new tools—including artificial intelligence, deep-learning methods, genetic tools and advanced neuroimaging—are making the largest impact?

The Janus face of NK cells in neurodevelopment

NK cells in neurodevelopment.

Maternal immune activation (MIA) during pregnancy perturbs fetal neurodevelopment, with natural killer (NK) cells emerging as key contributors to neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD).

Clinical studies consistently report NK cell dysfunction in ASD patients and their mothers, characterized by altered cytotoxicity, hyperactivation at rest, functional exhaustion on stimulation, and skewed receptor/genetic profiles.

Uterine NK (uNK) cells, indispensable for placental and fetal development, can paradoxically promote NDDs when hyperactivated, releasing granzyme B (GZMB) that disrupts fetal brain structure and function.

Elucidating the MIA-driven ‘uNK/ GZMB–microglia–NDD’ axis is essential to devise preventive strategies for high-risk pregnancies and identify early biomarkers of neurodevelopmental risk. sciencenewshighlights ScienceMission https://www.cell.com/cms/10.1016/j.it.2025.10.001/asset/89cd…ts/gr3.jpg https://sciencemission.com/Janus-face-of-NK-cells

Maternal immune activation (MIA), triggered by infection or inflammation during pregnancy, is a well-recognized risk factor for neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD). Clinical cohort studies and rodent models suggest that natural killer (NK) cells play a significant role in NDD pathogenesis, but the underlying mechanisms remain poorly defined. Here, we summarize the key immune mediators involved in MIA-induced NDDs, emphasizing microglia as a central hub. We then examine emerging evidence implicating aberrant NK cell activation in ASD, underscoring their overlooked contribution to impaired neurodevelopment. Finally, we discuss potential mechanisms of NK cell–microglia crosstalk in NDDs. Elucidating these interactions in the context of MIA will be crucial for developing preventive and therapeutic strategies against inflammation-driven NDDs.

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PARG inhibition halts cholangiocarcinoma progression via the Hippo pathway and enhances response to chemotherapy and immunotherapy

PARG inhibition potentiates the efficacy of chemotherapy and PD-1 blockade in murine cholangiocellular carcinoma models.

PARG (poly(ADP-ribose) glycohydrolase) plays a key role in cancer cells by regulating poly(ADP-ribose) turnover and DNA damage responses, thereby supporting genomic stability, transcriptional programs, and survival pathways that enable tumour growth and treatment resistance. Yu, Xie, Yu, Zhao, Xu, Yang, Wei and coworkers evaluated the role of PARG in the development, progression and resistance to therapy in cholangiocarcinoma. In a cohort of 275 patients with cholangiocellular carcinoma (CCA), they observed that the levels of PARG are hyperactivated in the tumour tissue, and higher levels of PARG are associated with worse prognosis. Pharmacological or genetic inhibition of PARG in murine CCA models suppresses tumour growth by activating the Hippo pathway, leading to YAP/TAZ inactivation and reduced proliferative and stemness programs in cholangiocarcinoma cells. Notably, PARG inhibition synergizes with standard chemotherapy and enhances responsiveness to immunotherapy in mice, suggesting a role in modulating tumour cell–intrinsic survival pathways and the tumour immune microenvironment. Key open questions include the safety and specificity of sustained PARG inhibition in chronic liver disease and whether Hippo pathway activation and immune sensitization observed in models will translate into durable clinical benefit in heterogeneous human tumours.

Full text here: https://www.journal-of-hepatology.eu/article/S0168-8278(…0/fulltext.

EASL — the home of hepatology.

Cholangiocarcinoma (CCA) is a lethal malignancy with limited therapeutic options. We investigated the oncogenic role of poly(ADP-ribose) glycohydrolase (PARG) and evaluated potential therapeutic strategies.

The “hard problem of consciousness” is actually easy

Slavoj Žižek, Carlo Rovelli, Alenka Zupančič debate subjectivity, and how it relates to the world around it.

What does the hard problem get wrong?

With a free trial, you can watch the full debate NOW at https://iai.tv/video/the-self-and-the… tend to think of ourselves as observers of the world and experience as something different from the material stuff that makes up reality. Yet at the same time as human beings, we are at once part of the universe and part of that reality. And this profoundly puzzling relationship, that we are both part of something and yet separate from it, has been at the centre of Western thought. Materialists claim there is only physical material. But if so, thought, experience, and consciousness become illusory. Idealists argue there is only consciousness, but then it is reality that becomes an illusion. While dualists hold that both the self and the world exist, but that the connection between the two is mysterious. Is the self part of the world or necessarily outside of it? Was Kant right that the distinction between subject and object is necessary for experience to be possible? Or are these deep metaphysical questions beyond us, and our theories and language incapable of uncovering the ultimate state of things? #zizek #philosophy #physics #consciousness #quantum #quantumphysics Slavoj Žižek is one of the most famous philosophers in the world and is the author of more than 50 books, including most recently at the time of the debate Zero Point. Alenka Zupančič is a leading Lacanian philosopher and social theorist. She is a professor at The European Graduate School and at the University of Nova Gorica. Joining from America, Carlo Rovelli is a leading theoretical physicist, the author of several best-selling books, and a founding figure in the field of quantum gravity. His recent book, Reality Is Not What It Seems, has ethical implications for the nature of the self and personal identity. Jack Symes hosts. 00:00 Introduction 00:37 Carlo Rovelli on reality 05:22 Alenka Zupančič: is our knowledge incomplete, or reality itself? 07:55 Slavoj Žižek: how can a stone have freedom? 09:28 Carlo Rovelli on freedom 11:17 Can we ever resolve the relationship between the self and the world around us? 11:35 The problem with David Chalmers The Institute of Art and Ideas features videos and articles from cutting edge thinkers discussing the ideas that are shaping the world, from metaphysics to string theory, technology to democracy, aesthetics to genetics. Subscribe today! https://iai.tv/subscribe?utm_source=Y… For debates and talks: https://iai.tv For articles: https://iai.tv/articles For courses: https://iai.tv/iai-academy/courses.

We tend to think of ourselves as observers of the world and experience as something different from the material stuff that makes up reality. Yet at the same time as human beings, we are at once part of the universe and part of that reality. And this profoundly puzzling relationship, that we are both part of something and yet separate from it, has been at the centre of Western thought. Materialists claim there is only physical material. But if so, thought, experience, and consciousness become illusory. Idealists argue there is only consciousness, but then it is reality that becomes an illusion. While dualists hold that both the self and the world exist, but that the connection between the two is mysterious.

Is the self part of the world or necessarily outside of it? Was Kant right that the distinction between subject and object is necessary for experience to be possible? Or are these deep metaphysical questions beyond us, and our theories and language incapable of uncovering the ultimate state of things?

#zizek #philosophy #physics #consciousness #quantum #quantumphysics.

Continue reading “The “hard problem of consciousness” is actually easy” | >

Clearing circular RNA from cells extends lifespan, C. elegans study reveals

Cells in our bodies produce RNA based on genetic information stored in DNA, and RNA serves as a blueprint for making proteins. Researchers at KAIST have discovered a new phenomenon: Removing “circular RNA” that accumulates in cells as we age can slow down aging and extend lifespan. This study provides crucial clues for uncovering the principles of aging and developing treatment strategies for related diseases.

Professor Seung-Jae V. Lee’s research team (RNA-Mediated Healthspan and Longevity Research Center) from the Department of Biological Sciences, in collaboration with research teams led by Professors Yoon Ki Kim and Gwangrog Lee, discovered the RNASEK protein —an enzyme that degrades circular RNA—plays a vital role in slowing aging and extending lifespan. The findings are published in the journal Molecular Cell.

Until now, circular RNA was primarily known as a “marker of aging” because of its high stability, causing it to accumulate in cells without being degraded as one ages. However, the molecular mechanism for removing this RNA and its direct link to aging had not been clearly identified. The research team conducted this study to determine how the accumulation of circular RNA affects aging and whether an intracellular management system exists to regulate it.

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