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Alzheimer’s may start with inflammation in the skin, lungs or gut

Alzheimer’s disease has long been viewed as something that originates inside the brain, but an in-depth genomic analysis suggests it may initially triggered by inflammation in distant organs like the skin, lungs or gut – perhaps decades before a person’s memory starts to decline.

This radical reframing of the disease may explain why Alzheimer’s drugs have been disappointing to date, because they act too late in the disease process. Instead, we may need to redirect our efforts towards addressing inflammation in other parts of the body.

“As neuroscientists, we tend to be very brain-centric, but this study really shines a spotlight on the fact that the brain is not disconnected from the rest of the body, and when changes happen in the rest of the body, it affects how the brain functions,” says Donna Wilcock at Indiana University, who wasn’t involved in the research. “Even though Alzheimer’s is a brain disease, we need to think about the whole body when we think about how it begins.”

Image: Alamy

The Alzheimer’s field is being turned on its head as mounting evidence points to the disease beginning outside the brain many years before symptoms start. This may mean we have to totally rethink how we approach preventing and treating the condition.

By Alice Klein

Continue reading “Alzheimer’s may start with inflammation in the skin, lungs or gut” | >

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.

Continue reading “In older adults, AML often follows clonal hematopoiesis mutations” | >

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.

The Day the Sky Wouldn’t Stop Exploding: the Mystery of the Ultra-Long Gamma-Ray Burst

On July 2, 2025, space telescopes monitoring the sky for brief, one-and-done flashes of high-energy light saw something that nobody expected: a gamma-ray burst (GRB) that came back again and again, stretching what is usually a single “burst” lasting seconds to minutes into an all-day event. NASA’s Fermi spacecraft triggered on multiple gamma-ray episodes from the same patch of sky over several hours, and other satellites soon reported compatible detections. Compared to the known population of GRBs that have been studied for decades, this was an outlier beast of a different species.

At first, the event’s location near the crowded plane of the Milky Way made it tempting to suspect something closer to home, located in our own Galaxy. But follow-up imaging overturned that assumption. Observations with the Very Large Telescope (VLT) in Chile narrowed down the position and, together with Hubble and JWST, revealed that the transient was coincident with a dusty, irregular host galaxy. The distance is extreme: the light from the explosion began its journey roughly 8 billion years ago. In other words, whatever happened was not a local flare—it was a truly cosmic-scale detonation, or, rather, a string of detonations.

The duration of this event was not the only weird thing about it. Archival data showed that low-energy X-rays were already present almost a day before the main gamma-ray fireworks—an “X-ray precursor” that is hard to reconcile with standard models of GRBs. Meanwhile, the gamma-ray behavior itself looked like a stuttering engine. Fermi detected a sequence of short flares separated by long gaps, collectively implying multi-hour activity from a central engine rather than the single, clean explosion typical of such events.

Long-Term Outcomes in Antibody-Negative Autoimmune EncephalitisA Systematic Review and Meta-Analysis

Long-term outcomes in antibody-negative autoimmune encephalitis: a systematic review and meta-analysis.

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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.

Alibaba’s Qwen 3

QWEN 3.5 running on iPhone Pro in airplane mode. Full large language model running onan edge device with no network connectivity.

5 is now running fully on device on an iPhone 17 Pro, and that’s a big deal.

Despite its compact size, Qwen 3.5 reportedly outperforms models up to four times larger. It shows strong multimodal capability, meaning it can interpret and reason over images as well as text. It also includes a reasoning toggle, letting users switch between faster responses and deeper step by step thinking depending on the task.

The demo uses a 2B parameter model quantized to 6 bit precision, optimized with MLX for Apple Silicon. That combination allows advanced AI to run locally, without relying on cloud servers.

If this scales, it signals a shift toward powerful, private, on device AI that doesn’t need a data center to compete.

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.

Chimps’ love for crystals could help us understand our own ancestors’ fascination with these stones

Crystals have repeatedly been found at archaeological sites alongside Homo remains. Evidence shows that hominins have been collecting these stones for as long as 780,000 years. Yet, we know that our ancestors did not use them as weapons, tools, or even jewelry. So why did they collect them at all?

Now, in a new study appearing in Frontiers in Psychology, scientists in Spain have investigated which characteristics of crystals may have made them so fascinating to our ancestors. They designed experiments with chimpanzees—one of the two great ape species most closely related to modern humans—to identify the physical properties of crystals that may have attracted early hominins.

“We show that enculturated chimpanzees can distinguish crystals from other stones,” said lead author Prof. Juan Manuel García-Ruiz, an Ikerbasque Research Professor of crystallography at the Donostia International Physics Center in San Sebastián. “We were pleasantly surprised by how strong and seemingly natural the chimpanzees’ attraction to crystals was. This suggests that sensitivity to such objects may have deep evolutionary roots.”

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