Although radioresistant and circulating tumor cell survival has been attributed to altered metabolism, the metabolic impact of radiation therapy on stromal cells is unknown. Corn et al. demonstrate radiation-induced mitochondrial and metabolic changes in fibroblasts that are regulated by autophagy and drive growth in triple-negative breast cancer.
The importance of diet and lifestyle in maintaining overall health has long been recognised. MicroRNAs (miRNAs) have emerged as key players in the intricate interplay between health and disease. This study, including 305 participants, examined the role of miRNAs from capillary blood as indicators of individual physiological characteristics, diet, and lifestyle influences. Key findings include specific miRNAs associated with inflammatory processes and dietary patterns. Notably, miR-155 was associated with subjects with metabolic diseases and upregulated in age. Additionally, the study revealed diet-related miRNA expressions: high consumption of vegetables, fruits, and whole grains correlated with increased levels of miR-let-7a and miR-328, both implicated in anti-inflammatory pathways, and decreased expression of pro-inflammatory miR-21.
Here, Dolly Mehta & team find loss of ERG in endothelial cells alters neutrophil transcriptome towards inflammatory lineage via IL8/CXCR2 and CXCR2 blockade with Reparixin reduces inflammation, neutrophil infiltration, and improves survival in a pneumonia model.
The figure shows mouse lungs 30 minutes after antibody administration, with increased number of neutrophils (green) in Erg-null mice compared with Ergfl/fl mice. Endothelium (red).
1Department of Pharmacology and Regenerative Medicine, and.
2Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois Chicago, College of Medicine, Chicago, Illinois, USA.
Address correspondence to: Dolly Mehta, Department of Pharmacology and Regenerative Medicine, University of Illinois, Chicago, College of Medicine, 835 S. Wolcott Avenue, Chicago, Illinois 60,612, USA. Phone: 312.355.0236; Email: [email protected].
The immune system’s B cells create antibodies that can mount a response against just about anything—either destroying a pathogen or instructing the rest of the immune system to go after the offender. But what happens when these antibodies malfunction?
Researchers at Boston Children’s Hospital have identified the previously unknown mechanism for how immune cells can go back and self-edit the genes that code for these antibodies, essentially recycling them into newer versions.
The workings of this new mechanism, published in Nature, were uncovered in the laboratory of Frederick Alt, Ph.D., of the Program in Cellular and Molecular Medicine at Boston Children’s and a Howard Hughes Medical Center Investigator.
Among the many promising possibilities of using CRISPR-based therapeutics, their translational use in monogenic human genetic diseases has the potential to provide long-term therapy after a single treatment. Genetic disorders can be treated with the help of CRISPR by editing the defective (disease-causing) gene or by editing the enhancer or regulator of the defective gene. Numerous studies, which are summarized in the table below (Table ), have shown promising results by using these two approaches.
3. Examples of CRISPR-Based Therapeuticsfor the Treatment of Genetic Disorders.
DiseaseCRISPR targetapproachmajor outcome of the studyreferenceDuchenne muscular dystrophydystrophin gene (DMD)single or multiplexed sgRNAs were developedto restore thedystrophin reading frame by targeting the mutational hotspot at exons45–55 and introducing shifts within exons or deleting one ormore exonsdystrophin expression is restored in vitroOusterout et al. Huntington’sdiseaseHuntingtin gene (HTT)HTT 5′ UTR was targetedimpropermaturation of the transcript and reducing the expressionof the disease-causing alleleKolli et al.a dual sgRNA approachwas used in vitro toexcise a 44kb promoter region upstream of a mutant HTT gene to silence its expressionexpression of the Huntington’sdisease-causing variant wasablatedShin et al.glaucomamyocilin gene (MYOC)Knocked down the expression of mutant MYOC in a mouse model of primary open-angle glaucomareductionof ER stress, lower intraocular pressure, and thepreventability of further glaucomatous damage in mouse eyes was observed. The authors also demonstrated the feasibility of utilizing CRISPR/Cas9in human eyes with glaucomaJain et al.hereditary tyrosinemiatype Ifumarylacetoacetate hydrolase gene (FAH)HDR-mediated point mutation correction in mouse hepatocytes.a significant proportion of alleles were correctedVanLith et al. Leber congenital amaurosis type 10 (LCA10)centrosomalprotein 290 gene (CEP290)AAV5-basedtherapy (EDIT-101) encapsulates Staphylococcusaureus Cas9 (SaCas9) and two sgRNAs targeting genomic locationsupstream and downstream of the intronic CEP290 pointmutation. The two sgRNAs enable cutting around the mutation to induceits removal or inversionnormal splicing of CEP290 pre-mRNA was restoredMaeder et al. Noonan syndromeleucine zipper like post translational regulator 1 gene (LZTR1)intron 16 of LZTR1 was targetedthe gene editing process could overcomethe disease phenotypeassociated with Noonan syndrome-associated cardiomyopathy in iPSC-derivedcardiomyocytes in vitroHanses et al. Angelman syndromeUBE3A-ATS Inc. RNAUBE3A-ATS Inc. RNA was targetedin cultured human neurons andin a mouse model of the diseasetargeting of UBE3A-ATSablated its function, leading to expressionof the paternal UBE3A gene and rescuing the diseasephenotypeWolter et al.congenital muscular dystrophy type 1A (MDC1A)laminin subunit alpha 1 gene (LAMA1)CRISPR activator mediated gene upregulation3.6-foldupregulation of LAMA1 was observedKemaladevi et al.genetic deafnesstransmembrane channel like 1gene (TMC1)non-homologous end joining(NHEJ)-mediated mutant Tmc alleledisruptiondeafness was prevented in mouse models upto one year postinjectionGyörgy et al.
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If all is random and our universe is the only universe, the chance existence of human awareness would seem incredible. Because the laws of physics would have to be so carefully calibrated to enable stars and planets to form and life to emerge, it would seem to require some kind of design. But there are other explanations.
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Sean Carroll is Homewood Professor of Natural Philosophy at Johns Hopkins University and fractal faculty at the Santa Fe Institute. His research focuses on fundamental physics and cosmology.
Today, we’re introducing Gemini Robotics-ER 1.6, a significant upgrade to our reasoning-first model that enables robots to understand their environments with unprecedented precision. By enhancing spatial reasoning and multi-view understanding, we are bringing a new level of autonomy to the next generation of physical agents.
This model specializes in reasoning capabilities critical for robotics, including visual and spatial understanding, task planning and success detection. It acts as the high-level reasoning model for a robot, capable of executing tasks by natively calling tools like Google Search to find information, vision-language-action models (VLAs) or any other third-party user-defined functions.
Gemini Robotics-ER 1.6 shows significant improvement over both Gemini Robotics-ER 1.5 and Gemini 3.0 Flash, specifically enhancing spatial and physical reasoning capabilities such as pointing, counting, and success detection. We are also unlocking a new capability: instrument reading, enabling robots to read complex gauges and sight glasses — a use case we discovered through close collaboration with our partner, Boston Dynamics.