Supplying LSD1 with FAD in pancreatic cancer: a matter of protein-protein interaction?

Lysine-specific demethylase 1 (LSD1) is a key regulator in cancer epigenetic, and its activity is reliant on flavin adenine dinucleotide (FAD) as a cofactor. In this study, we investigated the correlation between LSD1 and FAD synthase isoform 2 (FADS2) protein levels in pancreatic ductal adenocarcinoma (PDAC) cell lines. We first assessed LSD1 protein and mRNA levels in mutant p53-expressing PANC-1 and MiaPaCa2 cells and p53-null AsPc-1 cells, compared to human pancreatic ductal epithelial (HPDE) controls.

Hetero-Diels-Alder and CuAAC Click Reactions for Fluorine-18 Labeling of Peptides: Automation and Comparative Study of the Two Methods.

Radiolabeled peptides are valuable tools for diagnosis or therapies; they are often radiofluorinated using an indirect approach based on an F-18 prosthetic group. Herein, we are reporting our results on the F-18 radiolabeling of three peptides using two different methods based on click reactions. The first one used the well-known CuAAC reaction, and the second one is based on our recently reported hetero-Diels-Alder (HDA) using a dithioesters (thia-Diels-Alder) reaction.

Exploring the impact of flavin homeostasis on cancer cell metabolism.

Flavins and their associated proteins have recently emerged as compelling players in the landscape of cancer biology. Flavins, encompassing flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), serve as coenzymes in a multitude of cellular processes, such as metabolism, apoptosis, and cell proliferation. Their involvement in oxidative phosphorylation, redox homeostasis, and enzymatic reactions has long been recognized.

PvdL Orchestrates the Assembly of the Nonribosomal Peptide Synthetases Involved in Pyoverdine Biosynthesis in .

The pyoverdine siderophore is produced by to access iron. Its synthesis involves the complex coordination of four nonribosomal peptide synthetases (NRPSs), which are responsible for assembling the pyoverdine peptide backbone. The precise cellular organization of these NRPSs and their mechanisms of interaction remain unclear.

Multitarget μ-Opioid Receptor Agonists─Neuropeptide FF Receptor Antagonists Induce Potent Antinociception with Reduced Adverse Side Effects.

The design of bifunctional compounds is a promising approach toward the development of strong analgesics with reduced side effects. We here report the optimization of the previously published lead peptide , which contains opioid receptor agonist and neuropeptide FF receptor antagonist pharmacophores and is shown to induce potent antinociception and reduced side effects. We evaluated the novel hybrid peptides for their activity at MOP, NPFFR1, and NPFFR2 and selected four of them () for assessment of their acute antinociceptive activity in mice.

Design, Synthesis and Catalytic Activity of Protein Containing Thiotyrosine as an Active Site Residue.

Native chemical ligation is a key reaction in the toolbox of chemical methods for the synthesis of native and modified proteins. The catalysis of ligation is commonly performed by using small aryl-thiol molecules added at high concentrations. In this work, we incorporated thiotyrosine, a non-canonical amino acid containing an aryl-thiol moiety, into a designed cyclic protein « sans queue ni tête ».

Xanthurenic acid: A role in brain intercellular signaling.

Xanthurenic acid (XA) raises a growing multidisciplinary interest based upon its oxidizing properties, its ability to complex certain metal ions, and its detoxifier capacity of 3-hydroxykynurenine (3-HK), its brain precursor. However, little is still known about the role and mechanisms of action of XA in the central nervous system (CNS). Therefore, many research groups have recently investigated XA and its central functions extensively.

Amyloid engineering - how terminal capping modifies morphology and secondary structure of supramolecular peptide aggregates.

The effects of peptide N- and C-termini on aggregation behavior have been scarcely studied. Herein, we examine (105-115) peptide fragments of transthyretin (TTR) containing various functional groups at both termini and study their impact on the morphology and the secondary structure. We synthesized TTR(105-115) peptides functionalized with α-amino (H-), -acetyl-α-amino (Ac-) or ,-dimethyl-α-amino (DiMe-) groups at the N-terminus, and with amide (-NH) or carboxyl (-OH) functions at the C-terminus.

Kinetic solubility: Experimental and machine-learning modeling perspectives.

Kinetic aqueous or buffer solubility is important parameter measuring suitability of compounds for high throughput assays in early drug discovery while thermodynamic solubility is reserved for later stages of drug discovery and development. Kinetic solubility is also considered to have low inter-laboratory reproducibility because of its sensitivity to protocol parameters [1]. Presumably, this is why little efforts have been put to build QSPR models for kinetic in comparison to thermodynamic aqueous solubility.

HPV38 impairs UV-induced transcriptional activation of the IL-18 pro-inflammatory cytokine.

Here, we demonstrate that the direct binding of p53 on the IL-18 promoter region regulates its gene expression. However, the presence of E6 and E7 from human papillomavirus type 38 impairs this mechanism via a new inhibitory complex formed by DNA methyltransferase 1 (DNMT1)/PKR/ΔNp73α, which binds to the region formerly occupied by p53 in primary keratinocytes.

Measurements of jet multiplicity and jet transverse momentum in multijet events in proton-proton collisions at .

Multijet events at large transverse momentum () are measured at using data recorded with the CMS detector at the LHC, corresponding to an integrated luminosity of . The multiplicity of jets with that are produced in association with a high- dijet system is measured in various ranges of the of the jet with the highest transverse momentum and as a function of the azimuthal angle difference between the two highest jets in the dijet system. The differential production cross sections are measured as a function of the transverse momenta of the four highest jets.

Azimuthal correlations in Z +jets events in proton-proton collisions at .

The production of Z bosons associated with jets is measured in collisions at with data recorded with the CMS experiment at the LHC corresponding to an integrated luminosity of 36.3. The multiplicity of jets with transverse momentum is measured for different regions of the Z boson's , from lower than 10 to higher than 100.

Measurement of the mass dependence of the transverse momentum of lepton pairs in Drell-Yan production in proton-proton collisions at .

The double differential cross sections of the Drell-Yan lepton pair (, dielectron or dimuon) production are measured as functions of the invariant mass , transverse momentum , and . The observable, derived from angular measurements of the leptons and highly correlated with , is used to probe the low- region in a complementary way. Dilepton masses up to 1 are investigated.

CMS pythia 8 colour reconnection tunes based on underlying-event data.

New sets of parameter tunes for two of the colour reconnection models, quantum chromodynamics-inspired and gluon-move, implemented in the pythia  8 event generator, are obtained based on the default CMS pythia  8 underlying-event tune, CP5. Measurements sensitive to the underlying event performed by the CMS experiment at centre-of-mass energies and 13, and by the CDF experiment at 1.96 are used to constrain the parameters of colour reconnection models and multiple-parton interactions simultaneously.

Search for light Higgs bosons from supersymmetric cascade decays in collisions at .

A search is reported for pairs of light Higgs bosons () produced in supersymmetric cascade decays in final states with small missing transverse momentum. A data set of LHC collisions collected with the CMS detector at and corresponding to an integrated luminosity of 138 is used. The search targets events where both bosons decay into pairs that are reconstructed as large-radius jets using substructure techniques.

Bioactivated and PEG-Protected Circa 2 nm Gold Nanoparticles for in Cell Labelling and Cryo-Electron Microscopy.

Advances in cryo-electron microscopy (EM) enable imaging of protein assemblies within mammalian cells in a near native state when samples are preserved by cryogenic vitrification. To accompany this progress, specialized EM labelling protocols must be developed. Gold nanoparticles (AuNPs) of 2 nm are synthesized and functionalized to bind selected intracellular targets inside living human cells and to be detected in vitreous sections.

Myelin in Alzheimer's disease: culprit or bystander?

Alzheimer's disease (AD) is a neurodegenerative disorder with neuronal and synaptic losses due to the accumulation of toxic amyloid β (Αβ) peptide oligomers, plaques, and tangles containing tau (tubulin-associated unit) protein. While familial AD is caused by specific mutations, the sporadic disease is more common and appears to result from a complex chronic brain neuroinflammation with mitochondriopathies, inducing free radicals' accumulation. In aged brain, mutations in DNA and several unfolded proteins participate in a chronic amyloidosis response with a toxic effect on myelin sheath and axons, leading to cognitive deficits and dementia.

The E2F4/p130 Repressor Complex Cooperates with Oncogenic ΔNp73α To Inhibit Gene Expression in Human Papillomavirus 38 E6/E7-Transformed Keratinocytes and in Cancer Cells.

Tumor suppressor p53 and its related proteins, p63 and p73, can be synthesized as multiple isoforms lacking part of the N- or C-terminal regions. Specifically, high expression of the ΔNp73α isoform is notoriously associated with various human malignancies characterized by poor prognosis. This isoform is also accumulated by oncogenic viruses, such as Epstein-Barr virus (EBV), as well as genus beta human papillomaviruses (HPV) that appear to be involved in carcinogenesis.

Measurements of the associated production of a W boson and a charm quark in proton-proton collisions at .

Measurements of the associated production of a W boson and a charm ( ) quark in proton-proton collisions at a centre-of-mass energy of 8 are reported. The analysis uses a data sample corresponding to a total integrated luminosity of 19.7 collected by the CMS detector at the LHC.

Bioimaging Nucleic-Acid Aptamers with Different Specificities in Human Glioblastoma Tissues Highlights Tumoral Heterogeneity.

Nucleic-acid aptamers are of strong interest for diagnosis and therapy. Compared with antibodies, they are smaller, stable upon variations in temperature, easy to modify, and have higher tissue-penetration abilities. However, they have been little described as detection probes in histology studies of human tissue sections.

Gold labelling of a green fluorescent protein (GFP)-tag inside cells using recombinant nanobodies conjugated to 2.4 nm thiolate-coated gold nanoparticles.

Advances in microscopy technology have prompted efforts to improve the reagents required to recognize specific molecules within the intracellular environment. For high-resolution electron microscopy, conjugation of selective binders originating from the immune response arsenal to gold nanoparticles (AuNPs) as contrasting agents is the method of choice to obtain labeling tools. However, conjugation of the minimal sized 15 kDa nanobody (Nb) to AuNPs remains challenging in comparison to the conjugation of 150 kDa IgG to AuNPs.

The Human Point Mutation Induces Pain Hypersensitivity and Spontaneous Pain in Mice.

The voltage-gated sodium channel Nav1.7 is encoded by gene and plays a critical role in pain sensitivity. Several gain-of-function (GOF) mutations have been found in patients with small fiber neuropathy (SFN) having chronic pain, including the R185H mutation.

Observation of B (2S)K and B (2S)K decays.

Using a data sample of proton-proton collisions collected by the CMS experiment at the LHC in 2017 and 2018 with an integrated luminosity of , the and decays are observed with significances exceeding 5 standard deviations. The resulting branching fraction ratios, measured for the first time, correspond to and , where the last uncertainty in the first ratio is related to the uncertainty in the ratio of production cross sections of and mesons, .