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In older adults, AML often follows clonal hematopoiesis mutations

However, the pathogenic contribution of PTPN11 mutations has been unclear.

John C. Byrd & team reveal PTPN11 mutations in AML can be early events in the clonal evolution of disease development and are associated with variably differentiated myeloid cells, based on human and murine studies:

The figure shows lower survival of the Npm1cA/Ptpn11E76K mouse model.


1Medical Scientist Training Program, The Ohio State University, Columbus, Ohio, USA.

2Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA.

3Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital, Cincinnati, Ohio, USA.

MARK2 serves as a key regulator of host antiviral immunity through GEF-H1 phosphorylation

Key cytoplasmic sensors, including the RNA sensors RIG-I and melanoma differentiation-associated gene 5 (MDA5), along with the DNA sensor cyclic GMP-AMP synthase (cGAS), specifically recognize viral RNA and DNA.6,7 Upon nucleic acid detection, PRR adaptors (TRIF, MAVS, and STING) recruit kinases such as TBK1 and IKKε to initiate downstream signaling cascades.8,9,10 This process leads to the phosphorylation and activation of the transcription factor interferon regulatory factor 3 (IRF3), which subsequently translocates from the cytoplasm to the nucleus to trigger type I interferon (IFN-I; IFN-α/β) expression.11,12,13 The secreted IFNs then activate pathways that culminate in the expression of interferon-stimulated genes (ISGs), establishing an antiviral state in host cells.13

Guanine nucleotide exchange factor H1 (GEF-H1), encoded by Arhgef2, is a microtubule-associated protein (MAP) and plays a pivotal role in diverse cellular processes, including epithelial barrier permeability, cell cycle regulation, cell motility, polarization, and leukemic cell differentiation.14 Beyond its structural role, GEF-H1 contributes to inflammatory cytokine production, intracellular mycobacterial elimination, and macrophage-mediated antiviral defenses.15,16 Activation of GEF-H1 enhances RLR signaling through its interaction with TBK1, thereby promoting IFN-β induction in macrophages via a microtubule-dependent mechanism.15 Its regulation also extends beyond microtubule binding and involves phosphorylation-dependent mechanisms and dynamic protein-protein interactions.17,18,19,20,21,22,23 The RhoA-specific GEF activity of GEF-H1 is inhibited by its phosphorylation at Ser886 and Ser959, which is mediated by microtubule affinity-regulating kinase 2 (MARK2).24 Notably, here, MARK2 was also screened out to interact with GEF-H1 by immunoprecipitation and mass spectrometry (IP-MS) assays in A549 cells. MARK2 belongs to the evolutionarily conserved KIN1/PAR-1/MARK family of serine/threonine kinases, which are crucial for microtubule stability and cellular polarity from yeast to humans.25 All mammalian MARK family members (MARK1–4) share a conserved architecture, featuring an N-terminal catalytic domain, a central ubiquitin-associated domain, and a C-terminal kinase-associated domain.26,27 These kinases regulate microtubule dynamics by phosphorylating key MAPs, including TAU, MAP2, and MAP4.28,29 However, their roles in viral infections remain poorly understood.30

Given the importance of phosphorylation-dependent signaling in antiviral responses, we hypothesized that MARK2 may modulate innate immunity through interacting with GEF-H1. To test this, we employed a combination of in vitro and in vivo approaches, including MS-based interactome profiling, reporter gene assays, gene editing via CRISPR-Cas9, in vitro kinase assays, viral infection models in primary macrophages and cell lines, and mouse models of RNA and DNA virus infection. By elucidating the functional significance of the MARK2-GEF-H1-TBK1 signaling axis, this study aims to reveal a previously uncharacterized layer of innate immune regulation and identify potential targets for broad-spectrum antiviral strategies.

Overcoming ovarian cancer’s resistance to immunotherapy

Cells in our immune system are best known for providing security against external invaders such as bacteria and viruses. These immune cells also guard against internal threats, including cancerous tumors. Different forms of cancer cells and tumors have their own tricks for avoiding detection by the body’s security system altogether or otherwise sabotaging any attempts to muster an immune response. In the case of the most common and difficult-to-treat form of ovarian cancer, this ability to suppress the immune system also makes the cancer resistant to treatments known as immunotherapies that seek to supercharge immune cells.

“Even if you boost the capability of immune cells, a treatment will have limited success if the cells struggle to recognize and react to the tumor,” said David Schlaepfer, Ph.D., a professor in the department of OBGYN and Reproductive Sciences at the University of California San Diego Moores Cancer Center.

Cannabis Extracts Significantly Reduce Myofascial Pain

“These findings indicate the clinical potential of cannabinoids as a promising therapeutic alternative for managing TMD…” [ https://www.labroots.com/trending/cannabis-sciences/30277/ca…ial-pain-2](https://www.labroots.com/trending/cannabis-sciences/30277/ca…ial-pain-2)


Temporomandibular Disorder (TMD) consists of a myriad of conditions causing jaw pain and dysfunction and the muscles controlling jaw movement. One type of pain is myofascial pain, which is associated with deep, aching muscle pain around the jaw, often resulting in later neck and shoulder pain. Traditional treatments include self-care like eating soft foods and over-the-counter anti-inflammatories. But how can Delta-9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) be used to relieve myofascial pain in patients suffering from TMD?

Now, a team of researchers from Brazil might be one step closer to better understanding the role of cannabis in treating myofascial pain. For their study, which was recently published in the journal Clinics, the team investigated how a combination of THC and CBD drug therapy could be used to not only decrease myofascial pain while also enabling TMD patients to regain jaw function. Over a 90-day period, 20 adults suffering from myofascial pain due to TMD were given gradual increases of THC and CBD starting from 2mg and eventually 10mg near the end of the trial.

The goal of the study was to ascertain the role of THC and CBD on treating myofascial pain and improving jaw movement and function. In the end, the researchers found that not only did the participants report an approximate 90 percent reduction in pain, but they were able to open their jaws approximately 4 mm wider than before the THC/CBD treatment.

Beyond amyloid plaques: AI reveals hidden chemical changes across the Alzheimer’s brain

Scientists at Rice University have produced the first full, dye-free molecular atlas of an Alzheimer’s brain. By combining laser-based imaging with machine learning, they uncovered chemical changes that spread unevenly across the brain and extend beyond amyloid plaques. Key memory regions showed major shifts in cholesterol and energy-related molecules. The findings hint that Alzheimer’s is a whole-brain metabolic disruption—not just a protein problem.

The anatomy of pain and suffering in the brain and its clinical implications

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Chronic pain, with a prevalence of 20–30% is the major cause of human suffering worldwide, because effective, specific and safe therapies have yet to be developed. It is unevenly distributed among sexes, with women experiencing more pain and suffering. Chronic pain can be anatomically and phenomenologically dissected into three separable but interacting pathways, a lateral ‘painfulness’ pathway, a medial ‘suffering’ pathway and a descending pain inhibitory pathway. One may have pain(fullness) without suffering and suffering without pain(fullness). Pain sensation leads to suffering via a cognitive, emotional and autonomic processing, and is expressed as anger, fear, frustration, anxiety and depression.

Using tiny ripples at skin level to monitor for possible health problems below

Caltech scientists have developed a method that detects tiny, imperceptible movements at the surface of objects to reveal details about what lies beneath. By analyzing the physics of waves traveling across the surface of an object—whether that be a manufactured product or the human body—the new technique can determine both the stiffness and thickness of the underlying material or tissue. This lays the groundwork for the project’s ultimate goal of enabling inexpensive, at-home health monitoring using little more than a smartphone camera.

“There is information scattered all around us in plain sight that we just haven’t learned to tap into. Our work is trying to leverage that information to recover material properties from inside objects by studying tiny movements on the surface,” says Katie L. Bouman, professor of computing and mathematical sciences, electrical engineering, and astronomy at Caltech and both a Rosenberg Scholar and a Heritage Medical Research Institute (HMRI) Investigator.

Bouman and her colleagues from Caltech presented the technique, called visual surface wave elastography, and its medical applications in a paper presented at the International Conference on Computer Vision in Honolulu last fall. The lead authors are Alexander C. Ogren, Ph.D., and Berthy T. Feng, Ph.D., who completed the work while at Caltech.

Functional photoacoustic microscopy reaches super-resolution by tracking red blood cells

The brain relies on real-time delivery of oxygen and nutrients through its microvasculature, which threads through neural tissue like electrical wires. While modern imaging technologies allow researchers to follow the activity of individual neurons in the brain, they are not yet advanced enough to dissect the microvascular function at a comparable spatial scale. This gap hinders our understanding of cerebral small vessel disease and its contributions to cognitive impairment and dementia.

To address this challenge, a team of researchers at Washington University in St. Louis and Northwestern University, led by Song Hu, professor of biomedical engineering in the McKelvey School of Engineering, have developed super-resolution functional photoacoustic microscopy (SR-fPAM).

By tracking the movement and oxygenation-dependent color change of red blood cells, SR-fPAM allows researchers to image blood flow and oxygenation at single-cell resolution in the mouse brain, which bridges a critical gap in functional microvascular imaging and could provide new insight into microvascular health and disease, such as stroke, vascular dementia and Alzheimer’s disease.

Abstract: Challenging the dogma…

Here, Adrian Vella & team show hepatic resistance to glucagon’s effects on amino acid catabolism is not a significant factor in postprandial metabolism, regardless of obesity or hepatic steatosis: type2diabetes MASH Glucagon.


Address correspondence to: Adrian Vella, Endocrine Research Unit, Mayo Clinic College of Medicine, 200 First St. SW, 5–194 Joseph, Rochester, Minnesota 55,905, USA. Phone: 507.255.6515; Email: [email protected].

Find articles by Christie, H. in: | Google Scholar |

1Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, Minnesota, USA.

Universal Vaccine Blocks Viruses, Bacteria, And Allergies With a Nasal Spray

Imagine getting a nasal spray in the fall months that protects you from all respiratory viruses, including COVID-19, influenza, respiratory syncytial virus, and the common cold, as well as bacterial pneumonia and early spring allergens.


As vital as vaccines are, they can be frustratingly selective about their targets.

Scientists from institutions across the US have now developed a strikingly “universal” vaccine, which has protected mice against a range of viruses, bacteria, and even allergies.

The new GLA-3M-052-LS+OVA vaccine can be delivered as a nasal spray. Three doses protected mice from infection from SARS-CoV-2 and other coronaviruses for three months, and reduced the viral load in their lungs 700-fold, compared to unvaccinated mice.

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