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Organoid-derived alveolar cells differentiate on a stretchable microfluidic device and show force-dependent susceptibility to

Mechanical strain exacerbates Pseudomonas infection in an organoid-based pneumonia-on-a-chip model.

In this Research Letter, Geraldine Nouailles & team use an advanced human lung-on-a-chip model to show that increased mechanical strain can make the lungs more vulnerable to harmful bacteria such as Pseudomonas aeruginosa.

1Charité — Universitätsmedizin Berlin, Department of Infectious Diseases, Respiratory Medicine and Critical Care, Berlin, Germany.

2Bundeswehr Hospital Berlin, Department of Internal Medicine, Berlin, Germany.

3Universität Leipzig, ScaDS.AI, Institute for Medical Informatics, Statistics, and Epidemiology, Leipzig, Germany.

Specialized transporters relay lipids to cellular targets

In addition to providing energy, lipids are also essential building blocks of our cell membranes. However, despite their importance, they remain poorly understood. A research team has revealed for the first time the secrets of their transport within cells. Each lipid uses a limited number of proteins to move from its place of production to its place of action. The team has also compiled an inventory of the proteins involved in the transport of hundreds of lipids.

These findings, published in the journal Nature, provide a better picture of the functioning of our cells, as well as of many genetic and metabolic disorders, such as diabetes and Alzheimer’s disease.

Biologists brought together more than a hundred transfer proteins with hundreds of different lipids. The aim was to obtain the most comprehensive list possible of the ‘pairs’ formed between each protein and the lipids it can carry.

To do this, two experimental methods were combined. The first, carried out in a test tube, provides a highly controlled environment, while the second, which more closely corresponds to the inside of a cell, allows researchers to verify how these bonds are formed under near-real conditions. This is a world first on such a scale and at such a level of complexity. “The ‘‘couples’’ identified show that transfer proteins are not “buses” capable of transporting most lipids, but private chauffeurs with specific characteristics,” explains the senior author.

Scientists have been able to determine, using advanced mathematical models, how three transfer proteins recognise, among all lipids, those that they actually transport. ScienceMission sciencenewshighlights.

Low-input proteomics identifies vWF as a negative regulator of Tet2 mutant hematopoietic stem cell expansion

Jassinskaja, Bode et al. provide a multi-omics characterization of Tet2-mutated cells, including global proteomics revealing novel roles for extracellular matrix (ECM) molecules in selectively modifying self-renewal divisions. These findings point more broadly to physical and mechanical mediators of self-renewal, implicating integrins and cytokine signaling as extracellular drivers of clonal expansion.

T-DXd/Pertuzumab Earns Type II Application Validation in EU for HER2+ mBC

The EMA has validated a Type II Variation marketing authorization application for T-DXd plus pertuzumab in first-line unresectable or metastatic HER2-positive breast cancer.

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The marketing authorization was based on results from the DESTINY-Breast09 trial assessing T-DXd/pertuzumab in first-line HER2+ metastatic breast cancer.

Virus-Specific T Cells and Response to Checkpoint Inhibitors in PML

Patients with detectable virus-specific T cells before checkpoint inhibitor therapy in PML demonstrated better survival rates and functional recovery than those without.

Question Are pretreatment JC virus-and/or BK virus-specific T cells in the blood associated with the efficacy of immune checkpoint inhibitors (ICIs) in progressive multifocal leukoencephalopathy (PML)?

Findings In this cohort study of 111 patients with PML treated with ICIs, those with detectable virus-specific T cells (n = 21) had significantly higher response rates and longer survival than both T cell–negative patients (n = 22) and those with unknown status (n = 68).

Laser speed in 3D printing tunes atomic structure of high-entropy alloys

Next-generation technology requires next-generation materials that can be tailored to exact mission requirements. Additive manufacturing, or 3D printing, has already revolutionized industries like aerospace engineering by enabling previously unthinkable component designs. However, this technique has been largely limited to pre-existing metallic alloys. This is due to the inherent complexity of the process that leads to far-from-equilibrium microstructures and results in mechanical properties that are hard to predict.

New research on alloy microstructures

In a new study, scientists at Lawrence Livermore National Laboratory and their collaborators demonstrate a method to overcome the challenges of the traditional additive manufacturing process. By adjusting the speed of the laser in a compositionally complex alloy (also called high-entropy alloy), the team discovered a method to guide how the atoms settle as the metal solidifies, controlling the material’s properties directly at the atomic scale.

Brain neurons process salience, valence and value separately to understand what is important—and what isn’t

The sound of a fire alarm tells us to get out quickly to not get hurt, while the sight of a gas station sign can signal a chance to refuel. In everyday life, we learn to link cues we sense with what they mean, helping us avoid danger or find what we need. But how does the brain sort and prioritize all these cues and their significance to quickly guide our reactions to what we see, hear, feel and sense?

Following new research in mice, scientists hope to be closer to answering this question.

“A sensory cue, like the sound of an alarm, can be more or less attention-grabbing, feel positive or negative, and feel more or less important or motivating for us to act, depending on what outcome we associate with it. These aspects help define the significance we assign to environmental stimuli and are key to driving behavior and decision-making. But how the brain organizes this information to guide appropriate behaviors remains unclear,” explains Assistant Professor Daniel Jercog from the Department of Neuroscience at the University of Copenhagen.

Patients with Carpal Tunnel Syndrome show increased reliance on vision in reaching-to-grasp: a study of in-flight grasp kinematics in compressive nerve injury

Reach for this new ArticleinPress!(Michela Paroli et al. Bangor University)

The fluid efficiency of everyday hand actions such as reaching-to-grasp is underpinned by finely calibrated, anticipatory, in-flight control of the hand. Peripheral nerve dysfunction could affect this control. We used Carpal Tunnel Syndrome (CTS), a compressive neuropathy of the median nerve, as a model of nerve dysfunction. Whether CTS affects in-flight aspects of reaching-to-grasp is unknown. We compared kinematics of movements in CTS and healthy controls, using motion capture. We varied object properties to determine whether anticipatory signatures of reaching-to-grasp are preserved in CTS. We also examined the effect of removing visual feedback at movement onset. This manipulation forces greater reliance on non-visual control signals, which should highlight impairments due to CTS, while indexing how much movements rely on vision.

Shingles Vaccine Linked to Slower Biological Aging, Study Finds

Vaccines may do far more than prevent infections.

The way that some inoculations train your immune system could also reduce the risk of cancer, stroke, or heart attacks, and possibly guard against dementia.

New evidence shows that the shingles vaccine is linked to slower aging, with benefits that can last for several years after vaccination.

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