Wang et al. apply INVADEseq to probe intracellular bacteria in oral squamous cell carcinoma patients treated with neoadjuvant immunotherapy. They show that bacteria modulate immune efficacy, identify specific response predictors, and uncover the impact of bacteria on the communication between predictors and cDC1s.
Biologically informed plasma pTau217 thresholds improved diagnostic accuracy for amyloid PET positivity in patients with CKD and anemia vs a standard single cutoff, supporting cost-efficient biomarker implementation in AlzheimerDisease screening.
Question For plasma phosphorylated tau 217–based amyloid-β detection, does the strategy of using biological subgroup–specific optimal single cutoffs or a double cutoff better optimize diagnostic accuracy and cost efficiency?
Findings This cohort study found that subgroup-specific optimal cutoffs improved accuracy over the standard single cutoff, especially in chronic kidney disease (CKD) and anemia. Compared with a double cutoff, the optimal cutoff had similar or better accuracy in CKD with lower cost, whereas a double cutoff was slightly better in underweight and anemia but created intermediates; in obesity, a double cutoff remained superior.
Meaning Biologically optimized cutoffs offer a balanced, cost-efficient default, particularly in CKD and anemia, while a double cutoff retains advantages in obesity.
Researchers at The Jackson Laboratory (JAX), in collaboration with the Massachusetts Institute of Technology (MIT), have developed the first bandage-like microneedle patch that can sample the body’s immune responses painlessly from the skin. The device detects inflammatory signals within minutes and collects specialized immune cells within hours without the need for blood draws or surgical biopsies.
Already, the patch is helping researchers and clinicians study immune responses in aging and skin autoimmunity, including vitiligo and psoriasis. In the future, it could make it easier to track how people respond to vaccines, infections, and cancer therapies by complementing traditional blood tests and biopsies while being far easier on patients.
The study appears in Nature Biomedical Engineering.
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The prefrontal cortex (PFC) of our brain can properly perform its “braking” function to suppress impulses when excitatory and inhibitory signals are in balance. To investigate how chronic drug exposure disrupts this balance, the research team conducted cocaine administration experiments on mice. During this process, they tracked when inhibitory neurons in the PFC were activated and how they sent signals to downstream brain regions.
The experimental results showed that parvalbumin (PV) cells, which account for about 60–70% of the inhibitory neurons in the PFC, were highly active when the mice attempted to seek cocaine. However, when “extinction training”—training to stop seeking the drug—was conducted, the activity of these cells significantly decreased. This demonstrates that the activity patterns of PV cells are not permanently fixed by addiction but can be readjusted through the extinction process.
The research team confirmed that artificially suppressing PV cell activity significantly reduced cocaine-seeking behavior in mice. Conversely, activating these cells caused the drug-seeking behavior to persist even after the extinction process. This effect was specifically observed in drug-addiction behavior and did not appear with general rewards like sugar water. Furthermore, this phenomenon was not observed in somatostatin (SOM) cells—another type of inhibitory neuron—indicating that PV cells selectively regulate drug addiction behavior.
The team also identified the specific brain circuit through which these PV cells operate. Signals originating from the prefrontal cortex are transmitted to the reward circuit of the Ventral Tegmental Area (VTA), a key brain region related to reward. This pathway emerged as the central channel for regulating addiction behavior, determining whether or not to seek the drug again. In this process, PV neurons act as a “regulatory switch,” controlling the flow of signals to influence dopamine signaling and deciding whether to maintain or suppress addictive behavior. ScienceMission sciencenewshighlights.
Drug addiction carries an extremely high risk of relapse, as cravings can be reignited by minor stimuli even long after one has stopped using. Previously, this phenomenon was attributed to a decline in the function of the prefrontal cortex (PFC), which regulates impulses. However, a joint international research team has recently revealed that the cause of addiction relapse is not a simple decline in brain function, but rather an imbalance in specific neural circuits.
The researchers have identified the core principle by which specific inhibitory neurons in the prefrontal cortex regulate cocaine-seeking behavior.
Mosley et al. investigate the role of cytosolic DNA structure in activation of cGAS/STING by MSI colorectal cancers. They find MSI cytosolic DNA is enriched in G-quadruplexes, leading to more effective cGAS/STING activation. Micronuclei are less effective at activating cytotoxic T cells through cGAS/STING but increase IL-10 and Treg activation.
Marko et al. show that elevated insulin in obese mice suppresses adipocyte IRF4, which governs fat versus muscle preservation during 5:2 intermittent fasting (IF) with or without caloric restriction. During an acute fast in humans, obesity and elevated insulin promoted lean mass loss in males but not females.
https://doi.org/10.1172/jci.insight.
Robert A. Fenton & team show that a diet low in potassium causes bone loss in mice, effects that are attributable to altered calcium absorption by the kidney.
The figure shows deep learning instance segmentation model to identify kidney tubules and indicates low dietary K+ intake alters the abundance of the calcium-sensing receptor.
1Department of Biomedical Sciences, University of Veterinary Medicine, Vienna, Austria.
2Department of Biomedicine, Aarhus University, Aarhus, Denmark.
3Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
