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Introducing GPT-5.3-Codex-Spark

Codex-Spark is rolling out today as a research preview for ChatGPT Pro users in the latest versions of the Codex app, CLI, and VS Code extension. Because it runs on specialized low-latency hardware, usage is governed by a separate rate limit that may adjust based on demand during the research preview. In addition, we are making Codex-Spark available in the API for a small set of design partners to understand how developers want to integrate Codex-Spark into their products. We’ll expand access over the coming weeks as we continue tuning our integration under real workloads.

Codex-Spark is currently text-only at a 128k context window and is the first in a family of ultra-fast models. As we learn more with the developer community about where fast models shine for coding, we’ll introduce even more capabilities–including larger models, longer context lengths, and multimodal input.

Codex-Spark includes the same safety training as our mainline models, including cyber-relevant training. We evaluated Codex-Spark as part of our standard deployment process, which includes baseline evaluations for cyber and other capabilities, and determined that it does not have a plausible chance of reaching our Preparedness Framework threshold for high capability in cybersecurity or biology.

NuMA promotes constitutive heterochromatin compaction by stabilizing linker histone H1 on chromatin

The nuclear repeat length (NRL) was calculated using NRLfinder as previous publication.33 Briefly, read lengths were extracted and converted into a frequency histogram, which was then smoothed using a digital 6th-order Butterworth filter with a zero-phase shift and a cutoff frequency of 0.04 cycles/read. This cutoff was empirically optimized to reduce noise from mononucleosomal DNA winding artifacts. Local minima and maxima were identified from the first derivative of the filtered histogram, with the second peak maximum corresponding to the dinucleosomal periodicity. The NRL shift between conditions (e.g., control vs. NuMA-depleted HCT116 cells) was calculated the mean difference between the first two peak maxima of each sample. All analyses were performed in Python 3.9 with NumPy, SciPy, and Matplotlib libraries.

For chromatin-state modeling, we used the ChromHMM (v.1.19).32 The input data of ATAC-seq and RNA-seq reported in this manuscript was generated as described above. Additional input data including ChIP-seq for CTCF, H3K4me3, H3K27me3, H3K4me1, H3K36me3 and H3K9me3 were download from ENCODE (https://www.encodeproject.org). briefly, raw bam files were download and replicates were combined. BinarizeBam and LearnModel tools in ChromHMM was used to generate chromatin state model with default settings. Emissions parameters were visualized in R.

Spectrin coordinates cell shape and signaling essential for epidermal differentiation

Arad Soffer, Aishwarya Bhosale, Carien M. Niessen, Chen Luxenburg, Matthias Rübsam (Universität zu Köln) and colleagues identify spectrin as a central component of epithelial cortical actomyosin networks to control cortex mechanics and signaling.

Cell shape and fate are tightly linked, yet how the cortical cytoskeleton integrates regulation of shape and fate remains unclear. Using the multilayered epidermis as a paradigm for cell shape–guided changes in differentiation, we identify spectrin as an essential organizer of the actomyosin cortex to integrate transitions in cell shape with spatial organization of signaling. Loss of αII-spectrin (Sptan1) in mouse epidermis altered cell shape in all layers and impaired differentiation and barrier formation. High-resolution imaging and laser ablation revealed that E-cadherin organizes gradients of cortical actin and spectrin into layer-specific submembranous networks with discrete structural and mechanical properties that coordinate cell shape and fate. This layer-specific organization dissipates tension and, in upper layers, retains activated growth factor receptor EGFR and the calcium channel TRPV3 at the membrane to induce terminal differentiation. Together, these findings reveal how polarized organization of the cortical cytoskeleton directs transitions in cell shape and cell fate at the tissue scale necessary to establish epithelial barriers.

Activated CD38+ mast cells promote gastric cancer progression by suppressing CD8+ T cell cytotoxic activity through adenosine metabolism

Zhao et al. delineate the dynamic evolution of the gastric mucosal microenvironment and characterize diverse immune cell populations during gastric cancer progression under H. pylori infection. They identify and validate that H. pylori-associated activated mast cells promote gastric cancer through PGE2-and adenosine-mediated suppression of CD8+ T cell cytotoxicity.

Aging brains pile up damaged synaptic proteins in microglia

It is increasingly clear, though, that the loss of synapses—the flexible and adaptive relay stations central to our brains’ ability to think, learn, and remember—is central to the rise of cognitive decline and dementia in old age.

Now, researchers have discovered clues that may tie synapse loss to another hallmark of brain aging: the declining ability of brain cells to break down and recycle damaged proteins.

Published in Nature, the study shows that synaptic proteins are particularly susceptible to this age-related garbage-disposal problem: In old age, synaptic proteins break down much more slowly, they become more likely to pile up into the tangled clumps of protein characteristic of neurodegenerative disease, and they are more likely to make their way into microglia, immune cells that prune away damaged synapses.

Those findings are the latest in a series of discoveries that suggest new links between the brain’s waste management systems, microglia, and neurodegeneration—and they could yield new insights into human brain aging and neurodegeneration, said the study’s lead author. ScienceMission sciencenewshighlights.

Temporal evolution of GRB 240825A afterglow provides insight into origins of optically dark gamma-ray bursts

Researchers from the Yunnan Observatories of the Chinese Academy of Sciences have conducted a new study on the temporal evolution of the afterglow from gamma-ray burst GRB 240825A. The study offers new evidence to better understand the physical environment surrounding gamma-ray bursts and provides insights into the mechanisms that govern their afterglow emission. The findings were recently published in The Astrophysical Journal.

Long-duration gamma-ray bursts (LGRBs) are widely believed to form from the core collapse of massive stars, usually occurring in dense star-forming regions. NASA’s Swift satellite detected GRB 240825A on August 25, 2024, and observed an unusually bright optical counterpart.

Early measurements yielded an X-ray afterglow spectral index of 0.79 and a significantly softer optical afterglow spectral index of 2.48, compared with a typical value near 1. Under standard models, a gamma-ray burst is classified as “optically dark” when its observed optical afterglow flux falls below the level predicted from its X-ray spectral index.

A glaucoma drug may help prevent opioid relapse

An existing drug currently used to treat glaucoma, altitude sickness, and seizures may also have the potential to prevent relapse in opioid use disorder, according to a study by researchers at University of Iowa Health Care. The work is published in the journal Neuropsychopharmacology.

The UI researchers led by John Wemmie, MD, Ph.D., focused on the drug known as acetazolamide (AZD) because it blocks the activity of a brain enzyme called carbonic anhydrase 4 (CA4). Wemmie’s team had previously discovered that inhibiting CA4 in the whole brain, or just in its reward center (the nucleus accumbens), of mice, significantly reduced the brain changes that occurred after cocaine withdrawal. In addition, blocking the CA4 enzyme reduced drug-seeking behavior and relapse in the mice.

“What makes this approach promising is that it works in a completely different way from current treatments,” says Wemmie, a professor of psychiatry in the UI Carver College of Medicine. “Instead of targeting opioid receptors, AZD targets a different pathway involved in drug-induced synaptic changes and drug-seeking behavior. This could open the door to new therapies that help people stay in recovery by addressing the brain’s long-term response to drug use.”

Strategies for blood–brain barrier rejuvenation and repair

The blood–brain barrier (BBB) is a dynamic interface that tightly regulates the transport of substances from the blood into the brain. BBB dysfunction can occur with ageing and is a hallmark of many major diseases but is underappreciated as a therapeutic target. Here, Searson and Banks review studies on BBB repair and rejuvenation, highlighting common mechanisms across disorders and potential strategies for pharmacological intervention.

A Giant Star Vanished, And Scientists Think a Black Hole Is to Blame

One of the brightest stars in the Andromeda galaxy quietly collapsed into a black hole without any of the fanfare of a spectacular supernova.

What makes this startling discovery even more remarkable is that the first signs of the transformation were recorded back in 2014 – data that is crucial for understanding the different ways black holes can form after the death of a giant star.

“This has probably been the most surprising discovery of my life,” says astronomer Kishalay De of Columbia University in the US, who led the research. “The evidence of the disappearance of the star was lying in public archival data, and nobody noticed for years until we picked it out.”

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