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Sickle cell disease (SCD) is the most common genetic disease in the world and a societal challenge. SCD is characterized by multi-organ injury related to intravascular hemolysis. To understand tissue-specific responses to intravascular hemolysis and exposure to heme, we present a transcriptomic atlas in the primary target organs of HbSS vs HbAA transgenic SCD mice.
View Article and Find Full Text PDFDe novo design of peptide binders to conformationally diverse targets with contrastive language modeling.
Sci Adv
January 2025
Department of Biomedical Engineering, Duke University, Durham, NC, USA.
Designing binders to target undruggable proteins presents a formidable challenge in drug discovery. In this work, we provide an algorithmic framework to design short, target-binding linear peptides, requiring only the amino acid sequence of the target protein. To do this, we propose a process to generate naturalistic peptide candidates through Gaussian perturbation of the peptidic latent space of the ESM-2 protein language model and subsequently screen these novel sequences for target-selective interaction activity via a contrastive language-image pretraining (CLIP)-based contrastive learning architecture.
View Article and Find Full Text PDFTransgene-free genome editing in poplar.
New Phytol
January 2025
Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, 9052, Belgium.
Precise gene-editing methods are valuable tools to enhance genetic traits. Gene editing is commonly achieved via stable integration of a gene-editing cassette in the plant's genome. However, this technique is unfavorable for field applications, especially in vegetatively propagated plants, such as many commercial tree species, where the gene-editing cassette cannot be segregated away without breaking the genetic constitution of the elite variety.
View Article and Find Full Text PDFComparison of Lean, Obese, and Weight Loss Models Reveals TREM2 Deficiency Attenuates Breast Cancer Growth Uniquely in Lean Mice and Alters Clonal T Cell Populations.
Cancer Res
January 2025
Vanderbilt University, Nashville, TN, United States.
Obesity is an established risk factor for breast cancer development and poor prognosis. The adipose environment surrounding breast tumors, which is inflamed in obesity, has been implicated in tumor progression, and TREM2, a transmembrane receptor expressed on macrophages in adipose tissue and tumors, is an emerging therapeutic target for cancer. A better understanding of the mechanisms for the obesity-breast cancer association and the potential benefits of weight loss could help inform treatment strategies.
View Article and Find Full Text PDFIdentification of KRT16 and ANXA10 as cell cycle regulation genes for lung adenocarcinoma based on self-transcriptome sequencing of surgical samples and TCGA public data mining.
Discov Oncol
January 2025
Department of Geriatric Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China.
Aim: This study aimed to identify the genes associated with the development of lung adenocarcinoma (LUAD) and potential therapeutic targets.
Methods: Differentially expressed genes (DEGs) were identified by self-transcriptome sequencing of tumor tissues and paracancerous tissues resected during surgery and combined with The Cancer Genome Atlas (TCGA) data to screen for the genes associated with LUAD prognosis. The expression was validated at mRNA and protein levels, and the gene knockdown was used to examine the impact and underlying mechanisms on lung cancer cells.
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