Results 41 to 50 of about 77,146 (265)

Reconstructing enzyme evolution by protein engineering

open access: yesFEBS Letters, EarlyView.
Natural enzyme evolution can be retraced by protein engineering methods such as directed evolution, rational design, and ancestral sequence reconstruction. These approaches reveal how enzymes emerged from ligand‐binding scaffolds, developed varying substrate preferences, formed oligomeric complexes, adapted to environmental changes, and evolved novel ...
Lukas Drexler   +2 more
wiley   +1 more source

AscF in the mycobacterial CIII–CIV supercomplex lacks metal and nucleotide binding but links malate oxidation to respiration

open access: yesFEBS Letters, EarlyView.
The mycobacterial CIII‐CIV respiratory supercomplex is an obligate assembly, encompassing several subunits of unknown functions. We have characterized the intracellular subunit AscF, and show that it is unlikely to be a sensor for metals or nucleotides, but is required for growth on nonfermentable energy sources, and likely works as an adapter for ...
Eni Rile   +8 more
wiley   +1 more source

Establishment of a humanized patient‐derived xenograft mouse model of high‐grade serous ovarian cancer for preclinical evaluation of combination immunotherapy

open access: yesMolecular Oncology, EarlyView.
We have established a humanized orthotopic patient‐derived xenograft (Hu‐oPDX) mouse model of high‐grade serous ovarian cancer (HGSOC) that recapitulates human tumor–immune interactions. Using combined anti‐PD‐L1/anti‐CD73 immunotherapy, we demonstrate the model's improved biological relevance and enhanced translational value for preclinical ...
Luka Tandaric   +10 more
wiley   +1 more source

MITF maintains genome stability in nonmelanocyte lineages

open access: yesMolecular Oncology, EarlyView.
MITF is essential for melanocyte survival and acts as an oncogene in 10%–20% of melanomas. We show that MITF depletion causes genome instability in nonmelanocytic cells, leading to LATS2‐mediated P53 activation, cell cycle arrest, and apoptosis. This study highlights the role of MITF as a genome maintenance factor beyond the melanocyte lineage. Created
Drifa H. Gudmundsdottir   +13 more
wiley   +1 more source

Intrapatient tumour heterogeneity and clonal evolution in an autopsy study of metastatic salivary gland cancer

open access: yesMolecular Oncology, EarlyView.
Tumour heterogeneity and clonal evolution of metastatic salivary gland cancer were evaluated in two patients with adenoid carcinoma and one patient with myoepithelial carcinoma. Radiology‐guided autopsy enabled multi‐region sampling (total samples n = 149), followed by whole‐genome sequencing and phylogenetic reconstruction (17 tumour samples, 4–7 per ...
Gerben Lassche   +10 more
wiley   +1 more source

Long‐term hippocampal alterations and cognitive impairment in a murine model of surgical sepsis

open access: yesFEBS Open Bio, EarlyView.
Using a mouse model of surgical sepsis, we tested long‐term memory and analyzed the transcriptome of single cells isolated from the hippocampus. Survivor mice showed worse memory, loss of certain brain cell subpopulations, and abnormal immune cell activity—suggesting that post‐sepsis brain alterations may be linked to cognitive deficits.
Dong Seong Cho   +4 more
wiley   +1 more source

Derivation and characterization of retinal pigment epithelium from urine‐derived iPSCs

open access: yesFEBS Open Bio, EarlyView.
Age‐related macular degeneration causes vision loss via RPE dysfunction and loss. Traditional iPSC therapies rely on invasive biopsies, limiting scalability. Here, we utilize urine‐derived stem cells as an accessible source to generate u‐iPSCs, successfully differentiated into pigmented RPE. This “Urine‐to‐Retina” platform provides a promising path for
Daniella Beiner   +7 more
wiley   +1 more source

Molecular dynamics simulations of positively selected codons in FcγRI reveal novel biochemical binding properties

open access: yesFEBS Open Bio, EarlyView.
Evolutionary analysis across 32 placental mammals identified positive selection at residues H148 and W149 in the immune receptor FcγR1. Ancestral reconstruction combined with molecular dynamics simulations reveals how these mutations may influence receptor structure and dynamics, providing insight into the evolution of antibody recognition and immune ...
David A. Young   +7 more
wiley   +1 more source

Molecular characterization of covRS mutations in M1UK Streptococcus pyogenes

open access: yesFEBS Open Bio, EarlyView.
Group A Streptococcus (GAS) acquires covRS mutations driving a hypervirulent bacterial state, frequently associated with invasive disease‐like necrotizing fasciitis. We demonstrate that the newly emerged M1UK GAS lineage can also acquire these mutations.
Jarrad Pritchard   +12 more
wiley   +1 more source

Heterotropic regulation and negative homotropic cooperativity

open access: yesFEBS Open Bio, EarlyView.
We identified a structural module common to some proteins that couple negative cooperativity with heterotropic regulation, two features that rarely coexist. These proteins are ring‐like and present an ordered asymmetry whereby noncontacting subunits are symmetric, and their tertiary structure differs from that of contacting subunits.
Veronica Morea   +5 more
wiley   +1 more source

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