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A retrotransposon for site-specific gene transfer Nat. Biotechnol. (IF 46.9) Pub Date : 2024-03-18 Fred Dyda, Alison B. Hickman
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World’s first TIL therapy approved Nat. Biotechnol. (IF 46.9) Pub Date : 2024-03-15
Iovance Biotherapeutics has received a long-awaited go-ahead from the US Food and Drug Administration for its tumor-infiltrating lymphocyte (TIL) cancer therapy. The approval for Amtagvi (lifileucel) for treating patients with unresectable or metastatic melanoma is a milestone: it marks the first immune cell therapy approved for solid tumors, and it is also the first made from TILs. Amtagvi is a living
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The deubiquitinase function of ataxin-3 and its role in the pathogenesis of Machado-Joseph disease and other diseases Biochem. J. (IF 4.1) Pub Date : 2024-03-20 Potapenko, Anastasiya, Davidson, Jennilee M., Lee, Albert, Laird, Angela S.
Machado-Joseph disease (MJD) is a devastating and incurable neurodegenerative disease characterised by progressive ataxia, difficulty speaking and swallowing. Consequently, affected individuals ultimately become wheelchair dependent, require constant care, and face a shortened life expectancy. The monogenic cause of MJD is expansion of a trinucleotide (CAG) repeat region within the ATXN3 gene, which
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Supercharging T cell therapy with cancer mutations Nat. Biotechnol. (IF 46.9) Pub Date : 2024-03-15 Iris Marchal
T cell therapies are still hindered by poor T cell persistence and function, making them largely ineffective against solid tumors. Human cancerous T cells acquire mutations that increase their fitness and evade immune challenges in similar situations to those faced by therapeutic T cells. Writing in Nature, Garcia and colleagues exploit the fitness-enhancing abilities of these cancer mutations by incorporating
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US bill targets Chinese biotechs Nat. Biotechnol. (IF 46.9) Pub Date : 2024-03-15
The United States is seeking to prevent four Chinese biotech companies from doing business in the country, citing them as “companies of concern” that threaten national security. The Biosecure Act, introduced in both the Senate (S.3558) in December and House of Representatives (H.R.7085) in January, would prohibit the federal government from contracting with certain biotech providers connected to foreign
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Wearable technology and devices Nat. Biotechnol. (IF 46.9) Pub Date : 2024-03-15
Recent patents relating to wearable technology and devices for patient monitoring and treatment of health conditions.
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A synthetic antibiotic overcomes antimicrobial resistance Nat. Biotechnol. (IF 46.9) Pub Date : 2024-03-15 Iris Marchal
Many small-molecule antibiotics function by disrupting bacterial ribosomes, but bacteria develop resistance by modifying ribosomes to reduce the binding affinity of these molecules. Writing in Science, Wu et al. present a solution to this challenge by engineering a synthetic antibiotic that remains locked in an optimal conformation that boosts ribosomal binding. The authors designed the molecule cresomycin
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In vivo CRISPR agent cuts HAE attacks 95% Nat. Biotechnol. (IF 46.9) Pub Date : 2024-03-15
A CRISPR–Cas9-based gene editing therapy from Intellia Therapeutics reduced monthly swelling attacks by 95% in people with hereditary angioedema (HAE). The results from a small phase 1 trial were published in the New England Journal of Medicine in February. HAE is a rare genetic disorder characterized by recurrent bouts of subcutaneous and submucosal swelling that can be life threatening. Kallikrein
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Predicting the structure of large protein complexes Nat. Biotechnol. (IF 46.9) Pub Date : 2024-03-15 Iris Marchal
Deep learning models like RoseTTAFold and AlphaFold2 allow highly accurate protein structure prediction, but large protein assemblies remain hard to predict because of their size and complex subunit interactions. In a study published in Nature Methods, Shor and Scheidman-Duhovny introduce CombFold, a combinatorial and hierarchical assembly algorithm that predicts structures of large protein complexes
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Cell-based coffee future-proofs world’s favorite brew Nat. Biotechnol. (IF 46.9) Pub Date : 2024-03-15
Lior Raviv, Pluri’s chief technical officer, says: “We hypothesized we could take the cells from the plant and put them in a bioreactor [to grow coffee].” Through their work in cell therapy and cultivated meat, the Pluri team knew that not all cells like the same growing conditions. Taking plant cell samples, they made cell lines and, instead of growing them swirling around in suspension culture, they
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Biotech news from around the world Nat. Biotechnol. (IF 46.9) Pub Date : 2024-03-15
Saudi Arabia announces a plan to become a biotech leader in the Middle East and North Africa region by 2030 and an international biotech hub by 2040. Its National Biotechnology Strategy aims to grow the country’s capabilities in vaccines, biomanufacturing, genomics and plant optimization to increase job creation and drive economic growth and diversification. The Ministry of Health and Welfare invests
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People Nat. Biotechnol. (IF 46.9) Pub Date : 2024-03-15
Recent moves of note in and around the biotech and pharma industries.
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2H23 biotech job picture Nat. Biotechnol. (IF 46.9) Pub Date : 2024-03-15 Michael Francisco
A semiannual snapshot of job expansions, reductions and availability in the biotech and pharma sectors.
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Lighting the match: how a student-led career mentorship program can blaze the way for non-academic careers Nat. Biotechnol. (IF 46.9) Pub Date : 2024-03-15 Anna Bagnell, Alana MacDonald, Peter Espenshade, Mark Schenerman
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Biologic patent challenges under the America Invents Act Nat. Biotechnol. (IF 46.9) Pub Date : 2024-03-15 Victor L. Van de Wiele, Aaron S. Kesselheim, S. Sean Tu
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Innovators want pills to treat sickle cell disease. Can they match gene therapy? Nat. Biotechnol. (IF 46.9) Pub Date : 2024-03-15
Although CRISPR-based gene therapy for sickle cell disease offers transformative outcomes, drugmakers are striving to develop treatments that are easy to manufacture and can reach much larger numbers of patients.
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Accessing natural vaccine adjuvants Nat. Chem. Biol. (IF 14.8) Pub Date : 2024-03-15 Vincent Courdavault, Nicolas Papon
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Functional genomic screens with death rate analyses reveal mechanisms of drug action Nat. Chem. Biol. (IF 14.8) Pub Date : 2024-03-13 Megan E. Honeywell, Marie S. Isidor, Nicholas W. Harper, Rachel E. Fontana, Gavin A. Birdsall, Peter Cruz-Gordillo, Sydney A. Porto, Madison Jerome, Cameron S. Fraser, Kristopher A. Sarosiek, David A. Guertin, Jessica B. Spinelli, Michael J. Lee
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Glia-enriched cortical organoids implanted in mice capture astrocyte diversity Nat. Biotechnol. (IF 46.9) Pub Date : 2024-03-14
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De novo-designed transmembrane proteins bind and regulate a cytokine receptor Nat. Chem. Biol. (IF 14.8) Pub Date : 2024-03-13 Marco Mravic, Li He, Huong T. Kratochvil, Hailin Hu, Sarah E. Nick, Weiya Bai, Anne Edwards, Hyunil Jo, Yibing Wu, Daniel DiMaio, William F. DeGrado
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Novel modifications of PARP inhibitor veliparib increase PARP1 binding to DNA breaks Biochem. J. (IF 4.1) Pub Date : 2024-03-20 Velagapudi, Uday Kiran, Rouleau-Turcotte, Élise, Billur, Ramya, Shao, Xuwei, Patil, Manisha, Black, Ben E., Pascal, John M., Talele, Tanaji T.
Catalytic poly(ADP-ribose) production by PARP1 is allosterically activated through interaction with DNA breaks, and PARP inhibitor compounds have the potential to influence PARP1 allostery in addition to preventing catalytic activity. Using the benzimidazole-4-carboxamide pharmacophore present in the first generation PARP1 inhibitor veliparib, a series of 11 derivatives was designed, synthesized, and
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Breaking the deadlock in genetic code expansion Nat. Chem. Biol. (IF 14.8) Pub Date : 2024-03-11 Ya-Ming Hou, Yuko Nakano
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A solid beta-sheet structure is formed at the surface of FUS droplets during aging Nat. Chem. Biol. (IF 14.8) Pub Date : 2024-03-11 Leonidas Emmanouilidis, Ettore Bartalucci, Yelena Kan, Mahdiye Ijavi, Maria Escura Pérez, Pavel Afanasyev, Daniel Boehringer, Johannes Zehnder, Sapun H. Parekh, Mischa Bonn, Thomas C. T. Michaels, Thomas Wiegand, Frédéric H.-T. Allain
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High-throughput evaluation of genetic variants with prime editing sensor libraries Nat. Biotechnol. (IF 46.9) Pub Date : 2024-03-12 Samuel I. Gould, Alexandra N. Wuest, Kexin Dong, Grace A. Johnson, Alvin Hsu, Varun K. Narendra, Ondine Atwa, Stuart S. Levine, David R. Liu, Francisco J. Sánchez Rivera
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Target-locked: a mechanism for disaggregase binding to aggregated proteins J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-12 Trevor M. Morey, Walid A. Houry
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Loss of the glycosyltransferase Galnt11 affects vitamin D homeostasis and bone composition J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-12 E. Tian, Caroline Rothermel, Zachary Michel, Luis Fernandez de Castro, Jeeyoung Lee, Tina Kilts, Tristan Kent, Michael T. Collins, Kelly G. Ten Hagen
O-glycosylation is a conserved post-translational modification that impacts many aspects of organismal viability and function. Recent studies examining the glycosyltransferase Galnt11 demonstrated that it glycosylates the endocytic receptor megalin in the kidneys, enabling proper binding and reabsorption of ligands, including vitamin D binding protein (DBP). -deficient mice were unable to properly
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A selection and optimization strategy for single-domain antibodies targeting the PHF6 linear peptide within the Tau intrinsically disordered protein J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-12 Justine Mortelecque, Orgeta Zejneli, Séverine Bégard, Margarida C. Simões, Lea ElHajjar, Marine Nguyen, François-Xavier Cantrelle, Xavier Hanoulle, Jean-Christophe Rain, Morvane Colin, Cláudio M. Gomes, Luc Buée, Isabelle Landrieu, Clément Danis, Elian Dupré
The use of VHHs (Variable domain of the Heavy-chain of the Heavy-chain-only antibodies) as disease-modifying biomolecules in neurodegenerative disorders holds promises including targeting of aggregation-sensitive proteins. Exploitation of their clinical values depends however on the capacity to deliver VHHs with optimal physico-chemical properties for their specific context of use. We described previously
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Resolving the polycistronic aftermath: essential role of Topoisomerase IA in preventing R-loops in Leishmania J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-12 Payel Das, Arnab Hazra, Saradindu Saha, Sadhana Roy, Mandrita Mukherjee, Saugata Hazra, H.K. Majumdar, Somdeb BoseDasgupta
Kinetoplastid parasites are ‘living bridges’ in the evolution from prokaryotes to higher eukaryotes. The near-intronless genome of the kinetoplastid , exhibit polycistronic transcription which can facilitate R-loop formation. Therefore, to prevent such DNA-RNA hybrids has retained prokaryotic-like DNA Topoisomerase IA (LdTOPIA) in course of evolution. LdTOPIA is an essential enzyme which is expressed
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A small-molecule TNIK inhibitor targets fibrosis in preclinical and clinical models Nat. Biotechnol. (IF 46.9) Pub Date : 2024-03-08 Feng Ren, Alex Aliper, Jian Chen, Heng Zhao, Sujata Rao, Christoph Kuppe, Ivan V. Ozerov, Man Zhang, Klaus Witte, Chris Kruse, Vladimir Aladinskiy, Yan Ivanenkov, Daniil Polykovskiy, Yanyun Fu, Eugene Babin, Junwen Qiao, Xing Liang, Zhenzhen Mou, Hui Wang, Frank W. Pun, Pedro Torres Ayuso, Alexander Veviorskiy, Dandan Song, Sang Liu, Bei Zhang, Vladimir Naumov, Xiaoqiang Ding, Andrey Kukharenko, Evgeny
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Cardiomyocyte-specific deletion of GCN5L1 reduces lysine acetylation and attenuates diastolic dysfunction in aged mice by improving cardiac fatty acid oxidation Biochem. J. (IF 4.1) Pub Date : 2024-03-20 Stewart, Jackson E., Crawford, Jenna M., Mullen, William E., Jacques, Angelica, Stoner, Michael W., Scott, Iain, Thapa, Dharendra
Cardiac mitochondrial dysfunction is a critical contributor to the pathogenesis of aging and many age-related conditions. As such, complete control of mitochondrial function is critical to maintain cardiac efficiency in the aged heart. Lysine acetylation is a reversible post-translational modification shown to regulate several mitochondrial metabolic and biochemical processes. In the present study
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Fatty acid oxidation drives mitochondrial hydrogen peroxide production by α-ketoglutarate dehydrogenase. J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-11 Cathryn Grayson, Ben Faerman, Olivia Koufos, Ryan J. Mailloux
In the present study, we examined the mitochondrial hydrogen peroxide (mHO) generating capacity of α-ketoglutarate dehydrogenase (KGDH) and compared it to components of the electron transport chain (ETC) using liver mitochondria isolated from male and female C57BL6N mice. We show for the first time there are some sex dimorphisms in the production of mHO by ETC complexes I and III when mitochondria
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Refining the identity of mesenchymal cell types associated with murine periosteal and endosteal bone J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-11 Intawat Nookaew, Jinhu Xiong, Melda Onal, Cecile Bustamante-Gomez, Visanu Wanchai, Qiang Fu, Ha-Neui Kim, Maria Almeida, Charles A. O’Brien
Single-cell RNA sequencing has led to novel designations for mesenchymal cells associated with bone as well as multiple designations for what appear to be the same cell type. The main goals of this study were to increase the amount of single cell RNA sequence data for osteoblasts and osteocytes, to compare cells from the periosteum to those inside bone, and to clarify the major categories of cell types
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The Aryl Hydrocarbon Receptor Interacting Protein in cancer and immunity: Beyond a chaperone protein for the dioxin receptor J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-11 Sarah A. Kazzaz, John Tawil, Edward W. Harhaj
The aryl hydrocarbon receptor (AhR) interacting protein (AIP) is a ubiquitously expressed, immunophilin-like protein best known for its role as a co-chaperone in the AhR-AIP-Hsp90 cytoplasmic complex. In addition to regulating AhR and the xenobiotic response, AIP has been linked to various aspects of cancer and immunity that will be the focus of this review article. Loss of function AIP mutations are
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Analysis of pressure activated Piezo1 open and subconductance states at a single channel level. J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-11 Ghanim Ullah, Elena D. Nosyreva, David Thompson, Victoria Cuello, Luis G. Cuello, Ruhma Syeda
Mechanically activated Piezo1 channels undergo transitions from closed to open-state in response to pressure and other mechanical stimuli. However, the molecular details of these mechanosensitive gating transitions are unknown. Here, we used cell-attached pressure-clamp recordings to acquire single channel data at steady-state conditions (where inactivation has settled down), at various pressures and
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KcsA-Kv1.x chimeras with complete ligand binding sites provide improved predictivity for screening selective Kv1.x blockers J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-11 Patrik Szekér, Tamás Bodó, Katalin Klima, Ágota Csóti, Nikoletta Ngo Hanh, József Murányi, Anna Hajdara, Tibor Gábor Szántó, György Panyi, Márton Megyeri, Zalán Péterfi, Sándor Farkas, Norbert Gyöngyösi, Péter Hornyák
Despite significant advances in the development of therapeutic interventions targeting autoimmune diseases and chronic inflammatory conditions, lack of effective treatment still poses a high unmet need. Modulating chronically activated T cells through the blockade of the Kv1.3 potassium channel is a promising therapeutic approach, however, developing selective Kv1.3 inhibitors is still an arduous task
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Novel class of peptides disintegrating biological membranes to aid in the characterization of membrane proteins J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-11 Václav Hořejší, Pavla Angelisová, Jana Pokorná, Tatsiana Charnavets, Oldřich Benada, Tomáš Čajka, Tomáš Brdička
Styrene-maleic acid (SMA) and similar amphiphilic copolymers are known to cut biological membranes into lipid nanoparticles/nanodiscs containing membrane proteins apparently in their relatively native membrane lipid environment. Our previous work demonstrated that membrane raft microdomains resist such disintegration by SMA. The use of SMA in studying membrane proteins is limited by its heterogeneity
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Acidity of persulfides and its modulation by the protein environments in sulfide quinone oxidoreductase and thiosulfate sulfurtransferase J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-11 Dayana Benchoam, Ernesto Cuevasanta, Joseph V. Roman, Ruma Banerjee, Beatriz Alvarez
Persulfides (RSSH/RSS) participate in sulfur metabolism and are proposed to transduce hydrogen sulfide (HS) signaling. Their biochemical properties are poorly understood. Herein, we studied the acidity and nucleophilicity of several low molecular weight persulfides using the alkylating agent, monobromobimane. The different persulfides presented similar p values (4.6-6.3) and pH-independent rate constants
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Aerobic glycolysis comes with an enzyme cost but robustness gain Nat. Chem. Biol. (IF 14.8) Pub Date : 2024-03-08
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DNA-functionalized artificial mechanoreceptor for de novo force-responsive signaling Nat. Chem. Biol. (IF 14.8) Pub Date : 2024-03-06 Sihui Yang, Miao Wang, Dawei Tian, Xiaoyu Zhang, Kaiqing Cui, Shouqin Lü, Hong-hui Wang, Mian Long, Zhou Nie
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Genome-wide CRISPR activation screen identifies JADE3 as an antiviral activator of NF-kB dependent IFITM3 expression J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-09 Moiz Munir, Aaron Embry, John G. Doench, Nicholas S. Heaton, Craig B. Wilen, Robert C. Orchard
The innate immune system features a web of interacting pathways that require exquisite regulation. To identify novel nodes in this immune landscape we conducted a gain of function, genome-wide CRISPR activation screen with influenza A virus. We identified both appreciated and novel antiviral genes, including JADE3 a protein involved in directing the histone acetyltransferase HBO1 complex to modify
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YTHDF2 protein stabilization by the deubiquitinase OTUB1 promotes prostate cancer cell proliferation via PRSS8 mRNA degradation J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-09 Xuefeng Zhao, Suli Lv, Neng Li, Qingli Zou, Lidong Sun, Tanjing Song
Prostate cancer is a leading cause of cancer-related mortality in males. Dysregulation of RNA Adenine N-6 methylation (m6A) contributes to cancer malignancy. m6A on mRNA may affect mRNA splicing, turnover, transportation and translation. m6A exerts these effects, at least partly, through dedicated m6A reader proteins, including YTHDF2. YTHDF2 is necessary for development while its dysregulation is
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The Integrated Stress Response in metabolic adaptation J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-09 Hyung Don Ryoo
The Integrated Stress Response (ISR) refers to signaling pathways initiated by stress-activated eIF2‹ kinases. Distinct eIF2‹ kinases respond to different stress signals, including amino acid deprivation and mitochondrial stress. Such stress-induced eIF2‹ phosphorylation attenuates general mRNA translation and, at the same time, stimulates the preferential translation of specific downstream factors
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O-GlcNAcylation stimulates the deubiquitination activity of USP16 and regulates cell cycle progression J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-09 Jianxin Zhao, Jie Hua, Yahui Zhan, Chunxu Chen, Yue Liu, Liqian Yang, Haiying Wang, Hengbin Wang, Jing Li
Histone 2A monoubiquitination (uH2A) underscores a key epigenetic regulation of gene expression. In this report, we show that the deubiquitinase (DUB) for uH2A, Ubiquitin Specific Peptidase 16 (USP16), is modified by O-linked N-acetylglucosamine (O-GlcNAc). O-GlcNAcylation involves the installation of the O-GlcNAc moiety to Ser/Thr residues. It crosstalks with Ser/Thr phosphorylation, affects protein-protein
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Darkness inhibits autokinase activity of bacterial bathy phytochromes J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-09 Christina Huber, Merle Strack, Isabel Schultheiß, Julia Pielage, Xenia Mechler, Justin Hornbogen, Rolf Diller, Nicole Frankenberg-Dinkel
Bathy phytochromes are a subclass of bacterial biliprotein photoreceptors that carry a biliverdin IXα chromophore. In contrast to prototypical phytochromes that adopt a red-light absorbing Pr ground state, the far-red light absorbing Pfr-form is the thermally stable ground state of bathy phytochromes. Although the photobiology of bacterial phytochromes has been extensively studied since their discovery
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Big data and benchmarking initiatives to bridge the gap from AlphaFold to drug design Nat. Chem. Biol. (IF 14.8) Pub Date : 2024-03-08 Matthieu Schapira, Levon Halabelian, Cheryl H. Arrowsmith, Rachel J. Harding
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Hijacking endogenous mRNA for genetic code expansion Nat. Chem. Biol. (IF 14.8) Pub Date : 2024-03-07 Tomohiro Doura, Yuma Matsuoka, Shigeki Kiyonaka
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Growing community across the C-suite Nat. Biotechnol. (IF 46.9) Pub Date : 2024-03-07
Women in biotech CEO positions now have resources and networks.
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Prediction of tumor-reactive T cell receptors from scRNA-seq data for personalized T cell therapy Nat. Biotechnol. (IF 46.9) Pub Date : 2024-03-07 C. L. Tan, K. Lindner, T. Boschert, Z. Meng, A. Rodriguez Ehrenfried, A. De Roia, G. Haltenhof, A. Faenza, F. Imperatore, L. Bunse, J. M. Lindner, R. P. Harbottle, M. Ratliff, R. Offringa, I. Poschke, M. Platten, E. W. Green
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Reporter cell lines to screen for inhibitors or regulators of the KRAS-RAF-MEK1/2-ERK1/2 pathway Biochem. J. (IF 4.1) Pub Date : 2024-03-20 Weatherdon, Laura, Stuart, Kate, Cassidy, Megan, de la Gándara, Alberto Moreno, Okkenhaug, Hanneke, Muellener, Markus, Mckenzie, Grahame, Cook, Simon J., Gilley, Rebecca
The RAS-regulated RAF–MEK1/2–ERK1/2 signalling pathway is activated in cancer due to mutations in RAS proteins (especially KRAS), BRAF, CRAF, MEK1 and MEK2. Whilst inhibitors of KRASG12C (lung adenocarcinoma) and BRAF and MEK1/2 (melanoma and colorectal cancer) are clinically approved, acquired resistance remains a problem. Consequently, the search for new inhibitors (especially of RAS proteins), new
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Restricted glycolysis is a primary cause of the reduced growth rate of zinc-deficient yeast cells J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-07 Colin W. MacDiarmid, Janet Taggart, Michael Kubisiak, David J. Eide
Zinc is required for many critical processes, including intermediary metabolism. In , the Zap1 activator regulates the transcription of ∼80 genes in response to Zn supply. Some Zap1-regulated genes are Zn transporters that maintain Zn homeostasis, while others mediate adaptive responses that enhance fitness. One adaptive response gene encodes the 2-cysteine peroxiredoxin Tsa1, which is critical to
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Cancer-associated Polybromo-1 bromodomain 4 missense variants variably impact bromodomain ligand binding and cell growth suppression J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-07 Karina L. Bursch, Christopher J. Goetz, Guanming Jiao, Raymundo Nuñez, Michael D. Olp, Alisha Dhiman, Mallika Khurana, Michael T. Zimmermann, Raul A. Urrutia, Emily C. Dykhuizen, Brian C. Smith
The Polybromo, BRG1-associated factors (PBAF) chromatin remodeling complex subunit Polybromo-1 (PBRM1) contains six bromodomains that recognize and bind acetylated lysine residues on histone tails and other nuclear proteins. PBRM1 bromodomains thus provide a link between epigenetic post-translational modifications and PBAF modulation of chromatin accessibility and transcription. As a putative tumor
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Purinergic signaling promotes premature senescence J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-07 Daniela Volonte, Cory J. Benson, Stephanie L. Daugherty, Jonathan M. Beckel, Mohamed Trebak, Ferruccio Galbiati
Extracellular ATP activates P2 purinergic receptors. Whether purinergic signaling is functionally coupled to cellular senescence is largely unknown. We find that oxidative stress induced release of ATP and caused senescence in human lung fibroblasts. Inhibition of P2 receptors limited oxidative stress-induced senescence, while stimulation with exogenous ATP promoted premature senescence. Pharmacological
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Mitochondrial ATP generation is more proteome efficient than glycolysis Nat. Chem. Biol. (IF 14.8) Pub Date : 2024-03-06 Yihui Shen, Hoang V. Dinh, Edward R. Cruz, Zihong Chen, Caroline R. Bartman, Tianxia Xiao, Catherine M. Call, Rolf-Peter Ryseck, Jimmy Pratas, Daniel Weilandt, Heide Baron, Arjuna Subramanian, Zia Fatma, Zong-Yen Wu, Sudharsan Dwaraknath, John I. Hendry, Vinh G. Tran, Lifeng Yang, Yasuo Yoshikuni, Huimin Zhao, Costas D. Maranas, Martin Wühr, Joshua D. Rabinowitz
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Near-cognate tRNAs increase the efficiency and precision of pseudouridine-mediated readthrough of premature termination codons Nat. Biotechnol. (IF 46.9) Pub Date : 2024-03-06 Nan Luo, Qiang Huang, Liting Dong, Wenqing Liu, Jinghui Song, Hanxiao Sun, Hao Wu, Yuan Gao, Chengqi Yi
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Common and varied molecular responses of Escherichia coli to five different inhibitors of the lipopolysaccharide biosynthetic enzyme LpxC J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-06 Anna-Maria Möller, Melissa Vázquez-Hernández, Blanka Kutscher, Raffael Brysch, Simon Brückner, Emily C. Marino, Julia Kleetz, Christoph HR. Senges, Sina Schäkermann, Julia E. Bandow, Franz Narberhaus
A promising yet clinically unexploited antibiotic target in difficult-to-treat Gram-negative bacteria is LpxC, the key enzyme in the biosynthesis of lipopolysaccharides (LPS), which are the major constituents of the outer membrane. Despite the development of dozens of chemically diverse LpxC inhibitor molecules, it is essentially unknown how bacteria counteract LpxC inhibition. Our study provides comprehensive
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Strain-release alkylation of Asp12 enables mutant selective targeting of K-Ras-G12D Nat. Chem. Biol. (IF 14.8) Pub Date : 2024-03-05 Qinheng Zheng, Ziyang Zhang, Keelan Z. Guiley, Kevan M. Shokat
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After obesity drugs’ success, companies rush to preserve skeletal muscle Nat. Biotechnol. (IF 46.9) Pub Date : 2024-03-05
A growing number of companies are testing muscle-building agents to counter the side effects of dramatic weight loss and potentially to preserve lean muscle into old age.