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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.

How deadly Marburg virus enters human cells

The researchers also discovered a tiny antibody, called a nanobody, which mimics NPC1 at the receptor-binding site and can slip past a protective cap on Marburg’s entry protein, bind to it and block its attachment to the receptor. In lab tests, this nanobody prevented Marburg virus from entering cells. ScienceMission sciencenewshighlights.

In a new study published in Nature the researchers found that the Marburg virus (MBV), one of the world’s deadliest pathogens with an average 73% fatality rate, is unusually efficient at getting inside human cells. They also showed that the virus’s entry protein contains structural features that explain this efficiency and point to a strategy for blocking infection.

The researchers designed a tightly controlled system that enables a fair comparison of the entry proteins of Marburg and its relative Ebola. The team further found that the two viruses share the same human receptor. The authors determined structures of MBV glycoprotein (GP) in three states: unbound; bound to its endosomal receptor NPC1; and complexed with a neutralizing nanobody.

Marburg’s entry protein binds this receptor in a distinct orientation and with higher affinity, then changes shape in ways that help the virus enter cells. The authors show that the glycan cap shields the receptor-binding site from NPC1 but only partially from the nanobody, enabling limited immune evasion. After glycan cap cleavage, NPC1 binds to MBV GP in a distinct orientation compared with EBOV GP, providing an additional anchor and enhancing receptor affinity. NPC1 engagement also induces substantial conformational changes in MBV GP, probably facilitating membrane fusion. Using this approach, they showed that Marburg’s entry protein can drive viral entry into human cells up to 300 times more efficiently than Ebola’s.

New X-ray vision for electronics lets scientists monitor working chips remotely

A team of international researchers have developed a breakthrough way to observe what is happening inside electronic chips while they are operating—without touching them, taking them apart, or switching them off. The new technique uses terahertz waves, a safe and non-ionizing form of electromagnetic radiation, to detect tiny movements of electrical charge inside fully packaged semiconductor devices. For the first time, this allows scientists and engineers to monitor electronic components as they function in the real world.

The study, published in the IEEE Journal of Microwaves, involves researchers from Adelaide University in Australia, US technology company Virginia Diodes Inc, the Hasso Plattner Institute and the University of Potsdam, Germany.

Adelaide University Group Leader of the Terahertz Engineering Laboratory (TEL), Professor Withawat Withayachumnankul, said that semiconductors underpin almost every modern technology, from smartphones and medical devices to vehicles, power grids and defense systems.

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.

Protein modification in neurodegenerative diseases

The graphical abstract showcases the diversity of posttranslational modifications (PTMs) influencing protein structure and function. It features schematic representations of the following 10 prominent PTMs: phosphorylation (addition of phosphate groups), acetylation (addition of acetyl groups), methylation (addition of methyl groups), SUMOylation (attachment of SUMO proteins), ubiquitylation (attachment of ubiquitin molecules), succinylation (addition of succinyl groups), S-nitrosylation (attachment of NO), ADP-ribosylation (addition of ADP-ribose groups), glycosylation (addition of sugar molecules), and palmitoylation (attachment of palmitate groups).

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.

Liver Stiffness and All-Cause Mortality in Individuals With Diabetes

Liver stiffness identified by elastography was linked to a greater risk of death among adults with diabetes, suggesting elastography may help identify high-risk individuals.

Question Is a higher liver stiffness measurement (LSM), which indicates liver fibrosis, associated with an increase in all-cause mortality in unselected patients with diabetes?

Findings In this cohort study of 4,102 adults, high LSM was an independent risk factor for all-cause mortality in diabetes, even after a relatively short follow-up. Moreover, the coexistence of liver fibrosis and uncontrolled hemoglobin A1c level was associated with a higher risk of all-cause mortality compared with each condition individually.

Meaning Findings of this study suggest that using LSM to screen for liver fibrosis as part of routine diabetes management could aid in early identification of patients with high mortality risk.

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