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Category: evolution

Single-cell dissection of plasma cell clonal evolution to smoldering multiple myeloma after CD19 CAR-T cell therapy in B-cell acute lymphoblastic leukemia

Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized the treatment of B-cell malignancies, achieving deep and durable remissions in patients with B-cell acute lymphoblastic leukemia (B-ALL).1 Despite remarkable therapeutic successes, rare but clinically significant secondary hematologic malignancies have been reported during CAR-T cell therapy, often driven by lineage switching or clonal selection.2 Moreover, CAR-T cell therapy drives profound remodeling of the immune microenvironment, and the sustained inflammatory signaling may promote clonal evolution and influence disease progression.3 High-resolution approaches, such as single-cell RNA sequencing (scRNA-seq) and single-cell B-cell receptor sequencing (scBCR-seq), enable characterization of transcriptional programs, clonal identity, and temporal dynamics to dissect CAR-T cell therapy-induced clonal evolution and immune remodeling.4

Here, we report a case of B-ALL with B-cell receptor (BCR) heterogeneity at diagnosis that evolved into smoldering multiple myeloma (SMM) following CD19-targeted CAR-T therapy. The co-occurrence of B-ALL and SMM is exceptionally rare, as it requires malignant clones at distinct stages of B-cell development. This case provides a unique opportunity to dissect how CAR-T cell therapy drives B-lineage clonal evolution and reshapes the immune microenvironment. To this end, bone marrow mononuclear cells (BMMNC) were collected at multiple time points and subjected to longitudinal scRNA-seq and scBCR-seq to track dynamic changes in malignant and immune cell populations, thereby elucidating the mechanisms of clonal evolution and immune remodeling following CAR-T cell therapy. The patient gave informed consent and was enrolled in a clinical trial registered at clinicaltrials.gov (Identifier: NCT00123456).

Antibiotic cocktail made by soil bacteria can kill superbugs

In a study published in Nature today1, researchers report a ‘megacluster’ of genes in Streptomyces bacteria that target a key metabolic process in bacteria. Streptomyces is one of the most studied bacterial genera and produces many antibiotic compounds, including those used to produce streptomycin, the first effective antibiotic against tuberculosis.

“They’ve discovered something new in a system so extensively studied — hidden in plain sight,” says Mark Blaskovich, who works on antibiotic development at the University of Queensland in Brisbane, Australia. The gene cluster produces five compounds — four antibiotics and a protein — that target different stages of the production of biotin, or vitamin B7, which is essential for bacterial cell growth. “Since evolution has already optimized this combination, we may be able to leverage it to develop novel antibiotic combinations,” Blaskovich says.

It is much more difficult for bacteria to develop resistance to antibiotics that attack multiple parts of an essential metabolic pathway, explains Brendan Wren, a microbiologist at the London School of Hygiene & Tropical Medicine. The latest work could also lead to the discovery of gene clusters that produce antibiotic compounds involved in other metabolic processes.

Miasma Malware Targets npm Packages and GitHub Actions in Supply Chain Attack

Cybersecurity researchers have flagged yet another evolution of the supply chain attack linked to the Mini Shai-Hulud, Miasma, and Hades malware family that has compromised a new set of npm packages, even as it has propagated to the Go ecosystem.

“The latest activity includes malicious npm releases affecting LeoPlatform and RStreams packages, GitHub Actions workflow abuse, and a related Go module compromise involving the Verana Blockchain project,” Socket said.

The end goal of the campaign, as before, is to harvest developer or maintainer credentials and weaponize the stolen data to spread across package registries, repositories, and trusted developer workflows.

Molecular basis of human daylight vision

In a new study, the researchers have succeeded for the first time in determining the three-dimensional structure of human cone opsins in their dark state and showing how their molecular architecture enables their rapid activation by light. This provides important new insights into human vision and its evolution and may offer new starting points for the study of eye diseases that currently lack effective treatment. The study published in the journal Science.

Cone opsins are photoreceptor proteins found in the cone cells, which are densely packed in the fovea centralis. This area of the human retina is responsible for sharp vision. We humans have six to seven million cones in each eye. Their receptor proteins are activated by light, triggering a signalling cascade that ultimately produces electrical signals processed by the brain. Because this process is exceptionally fast, cone opsins enable us to track fast-moving objects with our eyes. However, they operate mainly during the day when the light levels are high. In low light, at dusk and at night, their evolutionarily younger relative, the rod opsin in rod cells, takes over this task.

Human colour vision is mediated by three types of cone opsins, each tuned to a different region of the visible spectrum. L cones are most sensitive to red light, M cones to green light, and S cones to blue light. Although there are only three cone types, we see the world in more than just three colours, as our colour perception arises from the interplay of their overlapping spectral sensitivities.

Out of darkness, blind Mexican cavefish illuminate brain evolution

Deep within the dark caves of northeastern Mexico lives a fish that has spent hundreds of thousands of years adapting to a world without light. The blind Mexican cavefish (Astyanax mexicanus) has evolved in perpetual darkness, losing its eyes and pigmentation while developing remarkable adaptations that help it survive in nutrient-poor environments.

Now, scientists are using this extraordinary species to uncover how evolution rewires the brain and shapes behavior. Because Astyanax exists both as sighted surface fish and as more than 30 independently evolved cave populations, researchers can directly compare how life in darkness alters sensory systems, neural circuits and behavior.

With new genetic tools and advanced imaging technologies that allow scientists to watch brain activity in real time, this unique fish is providing unprecedented insights into how animals adapt to extreme environments—and how evolution transforms the brain itself.

Michael Levin: “We Grew Little Creatures That Were Never Meant to Exist”

Creatures evolution never designed. Come geek out inside The Giant’s Shoulder Community. Ad Free exclusive content and much more → https://www.skool.com/the-giants-shou…

Michael Levin’s lab takes ordinary frog skin cells and lets them reassemble into beings that have never existed in the history of life — xenobots — and then a version with a core of neurons: neurobots. With no evolutionary history as a \.

When the Virus Knows the Answer Before We’ve Asked the Question : How Scientists Are Learning to Forecast Pandemics Before They Happen

Climate change as the macro engine for viral emergence The BA.3.2 “Cicada” variant’s hidden evolution Yeast-display technology and viral forecasting Pan-coronavirus vaccine development at La Jolla Institute How conserved viral regions unlock universal defenses.

Scientists can now force a virus to evolve in a test tube — and predict a pandemic before it starts. Heliox explores the 2026 yeast-display breakthrough that reproduced Omicron’s exact mutations in just two generations, connects it to the climate-driven migration of bat populations worldwide, and asks: are we approaching the day when we vaccinate against a pandemic that hasn’t happened yet?

An AAV variant selected through NHP screens robustly transduces the brain and drives secreted protein expression in NHPs and mice

Tecedor et al. used directed evolution to engineer AAVs with enhanced ependymal and brain delivery after injection into the cerebrospinal fluid. I think it would be interesting to try lumbar puncture delivery of these AAVs as well to see if they maintain decent biodistribution. (See my other post about Hinderer et al.’s paper: https://doi.org/10.1016/j.omtm.2020.04.012).

AAV capsid variants enriched for transduction of ventricular lining cells and brain parenchyma reduce the dose required for gene therapy to the CNS.

Investigating quantum and molecular plumbing in nanofluidics research

Our body contains an intricate system of tiny vessels through which blood, water and other molecules flow. When the size of the pipes shrinks to the nanoscale, where only a few molecules can fit side by side, the classical laws of physics governing the behavior of water are influenced by the atomic structure of the walls. “It’s not that classical hydrodynamics breaks down, but rather that it gets mixed with the condensed matter physics of the solid walls,” says Nikita Kavokine, tenure-track assistant professor and leader of the EPFL Quantum Plumbing Lab.

How liquids, and water in particular, behave at scales of a few nanometers is one of the big gaps in modern physics. For example, in some experiments, it has been observed that water flows through carbon nanotubes orders of magnitude faster than expected. Scientists are trying to understand phenomena that biology has mastered after millions of years of evolution.

“At the nanometer scale, our body leverages specific properties of water to filter molecules with high energy efficiency,” explains Kavokine. Aquaporins, for example, are protein channels embedded in cell membranes that use these molecular-scale interactions to let water pass while blocking ions and other molecules.

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