What happens to the brain during a Near-Death Experience? A new study discusses NDEs as adaptive mental states. Explore how the brain maintains complex consciousness during cardiac arrest and extreme failure.
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Scientists reveal a new way cancer cells survive DNA damage
A cancer drug target already being investigated in clinical trials turns out to be doing something even more consequential than researchers realized. Scientists at Scripps Research have discovered that the enzyme Pol theta (Polθ) drives a DNA repair mechanism directly at broken replication forks—one of the most frequent forms of DNA damage in cancer cells. The findings, published in Molecular Cell on March 16, 2026, help explain how tumors survive relentless replication stress and clarify why Pol theta inhibitors may be an effective strategy to selectively target cancer.
“We’ve uncovered a whole new dimension of how cancer cells cope with DNA damage at replication forks,” says Xiaohua Wu, professor at Scripps Research and senior author of the study.
Every time a cell divides, it must make an exact copy of its entire genome, a process carried out by molecular machinery that unzips the DNA double helix and reads each strand to build a new one. The point where this unzipping and copying actively happens is called a replication fork. But when this replication machinery encounters damage, forks can stall or collapse, leaving behind dangerous one-ended DNA breaks that are particularly difficult to repair and, if left unresolved, can kill the cell. This is particularly true in cancer cells, where replication stress is constant.
Gene signature predicting lung cancer recurrence
Using gene activity measurements, the researcher found more than 400 genes that differ between tumors with and without vascular invasion and confirmed these patterns in an independent cohort. They then developed and validated a machine-learning predictor that predicts whether vascular invasion is present. They found this test worked well at predicting tumor recurrence in other datasets and, crucially, gave accurate results about vascular invasion when measured in tiny biopsy samples taken before surgery.
The researchers believe this predictor will play an important role in picking a treatment matched to how aggressive the tumor is.
According to the researchers, there is growing evidence that vascular invasion is associated with poor prognosis in other kinds of cancer, such as breast, liver and gastric cancer. The researchers need to determine if the same genes that are active in vascular-invasive lung adenocarcinoma are altered in other cancers. ScienceMission sciencenewshighlights.
Lung cancer is the leading cause of death from cancer. It kills more people in the U.S. than breast, prostate and colon cancer combined. When lung adenocarcinoma, the most common primary lung cancer in the U.S., grows into nearby blood vessels (a process called vascular invasion), the tumor is more likely to recur even if surgically removed. Pathologists can identify areas of vascular invasion post-operatively, but surgeons could perform more extensive surgery to lower the risk of recurrence if they could predict which tumors were more likely to have vascular invasion.
Researchers believe they have, for the first time, identified genes whose activity changes in lung tumors with vascular invasion. Additionally, they also discovered that they could detect these changes in small pieces of the tumor collected during a presurgical biopsy procedure.
“We think this is a potential game changer for patients with early-stage lung cancer,” says the corresponding author. “Our findings suggest a simple biopsy-based test could help doctors better identify patients at higher risk of recurrence and guide treatment decisions.”
Abstract: Detailing the effects of a new therapeutic tuberculosis vaccine!
https://doi.org/10.1172/JCI196648 In this Research Article, Styliani Karanika & team report on an intranasal DNA vaccine that accelerates TB cure and achieves better outcomes than standard or drug-resistant regimens alone in preclinical models.
The figure shows mouse lungs with therapeutic intranasal Mip3a/relMt b fusion immunization, revealing local dendritic cell infiltration and enhanced colocalization with T cells.
1Center for Tuberculosis Research, Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
2W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
3Division of Hematological Malignancies, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University Hospital, Baltimore, Maryland, USA.
T-loop dynamics: telomere structure shapes cell fate decisions
Telomere structure shapes cell fate decisions.
Telomere loops (t-loops) are dynamic DNA structures, remodelled during the cell cycle and stress, rather than static protective caps.
The three-state model defines closed, intermediate, and uncapped telomeres, linking intermediate telomeres to programmed, fusion-resistant deprotection, which activates checkpoints without genome instability.
Mitotic arrest-dependent telomere deprotection is an active pathway in which Aurora B kinase drives t-loop unwinding without telomere shortening.
Aurora B kinase phosphorylation reprograms shelterin components (TRF1 and TRF2), enabling BTR-mediated t-loop dissolution and paradoxically converting protective factors into facilitators of deprotection.
T-loop dynamics reframe telomeres as responsive signalling hubs that couple chromosome architecture to genome surveillance and cell fate control. sciencenewshighlights ScienceMission https://sciencemission.com/T-loop-dynamics
Predicting Outcome After Newborn Stroke: A Lesion Network Mapping Study Leveraging Large-Scale Data
The development of cerebral palsy after neonatal stroke may be associated with disruptions of broad functional networks involving motor and extramotor regions as opposed to isolated lesions of the motor tracts.
Prior studies have established that resting-state networks are already present in newborns as early as term-equivalent age19 and that motor outcomes in healthy populations and other clinical populations are related to both primary motor networks and other broader motor networks.40,41 Our observation that the development of cerebral palsy correlated with both motor and extramotor regions lines up with these findings in other populations, and may indicate more widespread network vulnerabilities after stroke in neonates compared with adults.21 While it is known that disruption to primary motor regions is related to the development of cerebral palsy after NAIS,5,8 the extramotor regions (the frontal and temporal regions identified in the current study) may be more vulnerable to network-level disruptions in neonatal stroke due to the known relative immaturity of these regions during the neonatal period and their prolonged maturation to support higher-order functions.42,43 Particular vulnerability of these temporal and frontal regions has been demonstrated in other newborn, very preterm populations at risk of brain insult and injury.43
There are limitations to this study. Lesion network mapping has frequently been performed in adults and is more clinically feasible than directly acquiring resting-state fMRI scans in patients with NAIS; however, lesion network mapping may be seen as a less direct method for assessing brain connectivity.13,21,22 Functional connectivity has been well characterized in adults and neonates,1,16–19 but future studies will need to examine structural connectivity between regions via white matter fiber pathways using diffusion MRI scans to determine whether the functional changes identified correspond to structural changes.44 Such diffusion MRI investigations will be important in the future to investigate the roles (as part of global structural networks) of white matter regions and tracts such as the posterior limb of the internal capsule, which has previously been shown to be a strong predictor of motor outcome using individual region-based analyses.5–12 Given the paucity of prior research in this area, we aimed to establish that there is a relationship between the lesion functional connectome and cerebral palsy, but future work will also need to investigate the relative contributions of different measures (such as lesion volume, lesion location, and lesion functional and structural connectivity) to the development of cerebral palsy. Different measures may be more important for different brain regions (eg, lesions located in the primary motor regions are well-known to be related to cerebral palsy,5,8 whereas this study shows that functional connectivity of lesions to other subcortical and temporal and frontal cortical regions are related to cerebral palsy), meaning a combined approach considering multiple measures and regions may improve prediction of cerebral palsy in future work. Given that this study utilized clinically indicated MRIs from multiple sites for stroke participants, uniform scanner (eg, field strength) and sequence (eg, resolution) settings could not be used. The lesion network mapping approach does not necessarily require uniform scanning, making this approach more accessible. However, we acknowledge that variations in scanning parameters could influence some analysis steps, such as lesion segmentation and mapping to the template. To account for this, all analysis steps, including lesion segmentation and registration, were performed by experienced pediatric neurologists and image scientists, and outputs were extensively visually checked to ensure any poor-quality data were excluded.
This lesion network mapping approach identified correlations between lesions and the rest of the gray matter, which could include the equivalent lesion regions themselves (self-correlations, which are typically likely to be high). If self-correlations were very high in both groups (cerebral palsy and noncerebral palsy), then no significant group differences may be identified, which we think explains why the primary motor regions did not appear in the current findings (as the primary motor regions are key lesion regions affected by NAIS).5 The correlations identified between lesions and gray matter regions were positive (rather than negative correlations), which could reflect increased activity to support motor function (as opposed to decreased activity of irrelevant processes), as seen during task performance, but even intrinsically occurring at rest.45 Positive correlations are also, in general, stronger and less variable than negative correlations.46 We identified significant regions in both the left and right brain hemispheres; however, future work to specifically test whether there was a difference in the findings between hemispheres would be worthwhile (ie, to test whether results were greater in magnitude or spatial extent in the left or right hemisphere, which could be related to asymmetry in the lesions or connectome or both). With lesion network mapping, it was possible to infer that the regional networks identified correlated with cerebral palsy, but we cannot necessarily extrapolate on the relative importance of the individual regions of the network in cerebral palsy based on this method alone.13
Contribution of Life-Course Socioeconomic Position to Later-Life Brain Volumes in US Hispanic/Latino Adults
Among individuals with Schizophrenia and co-occurring SubstanceUseDisorders, psychological and psychosocial interventions showed limited benefit for symptom reduction and no effect on substance use, except for nicotine.
Question What is the efficacy of psychological and psychosocial interventions for individuals diagnosed with schizophrenia and comorbidity with substance use disorders?
Findings This systematic review and meta-analysis included 35 studies (4136 participants), with data available from 29 trials involving 3,831 participants covered in pairwise meta-analysis. Psychological and psychosocial interventions offered a very small effect on reducing patients’ overall symptoms, and no difference was found between intervention and control groups in reduction of all types of substance use intake or when separately analyzed, whereas nicotine use showed a modest improvement.
Meaning Current psychological and psychological interventions provide limited benefit for symptom reduction and were largely ineffective in decreasing substance use, except for a slight positive effect on nicotine use, indicating that more effective treatment strategies are urgently needed.
Cellular reprogramming beyond pluripotency
Aging, once viewed as an irreversible process, is now considered a modifiable process. Recent advances in cellular reprogramming reveal that transient expression of reprogramming factors can reverse molecular hallmarks of aging while preserving somatic cell identity. This ‘partial reprogramming’ rejuvenates tissues, restores regenerative capacity, and, in some models, extends lifespan without the tumorigenic risks of full dedifferentiation. In this review, we summarize genetic and chemical strategies for partial reprogramming, discuss their tissue-specific effects in vivo, and evaluate their implications for tissue regeneration and age-related disease. We further examine key challenges for clinical translation, including safety, delivery strategies, and temporal control of reprogramming.
Interstitial Lung Disease as a Late Occurrence in Ocrelizumab-Treated Patients With Multiple Sclerosis
Among patients with multiple sclerosis treated long-term with ocrelizumab, interstitial lung disease developed after a mean of 10.5 years, mainly as organizing pneumonia with variable outcomes.
This case series describes 6 cases of interstitial lung disease among patients with multiple sclerosis receiving long-term treatment with ocrelizumab.
‘Oldest octopus’ fossil is no octopus at all, scans reveal
A famous 300-million-year-old fossil that was thought to be the world’s oldest octopus—even featuring in the Guinness Book of Records—has turned out to be something else altogether. In what amounts to a case of mistaken identity, the fossil hid its true nature through decay 300 million years ago, before being fossilized.
Using the latest synchrotron imaging to search inside the fossil rock, researchers discovered tiny teeth preserved inside the rock that prove that Pohlsepia mazonensis is not an octopus at all, but an animal related to a modern Nautilus—a multi-tentacled animal with an external shell.
This revelation, revealed in the journal Proceedings of the Royal Society B, solves a long-running puzzle in the understanding of octopus evolution that has confused scientists for decades. It also provides evidence of the oldest nautiloid soft tissue preservation known in the fossil record and means that the record-holding “oldest octopus” should be quietly written out of the Guinness Book of Records.