Although graphite is known as one of the most chemically inert materials, we have found that graphene, a single atomic plane of graphite, can react with atomic hydrogen, which transforms this highly ...conductive zero-overlap semimetal into an insulator. Transmission electron microscopy reveals that the obtained graphene derivative (graphane) is crystalline and retains the hexagonal lattice, but its period becomes markedly shorter than that of graphene. The reaction with hydrogen is reversible, so that the original metallic state, the lattice spacing, and even the quantum Hall effect can be restored by annealing. Our work illustrates the concept of graphene as a robust atomic-scale scaffold on the basis of which new two-dimensional crystals with designed electronic and other properties can be created by attaching other atoms and molecules.
Traditional immunohistochemistry (IHC) has already become an essential method of diagnosis and therapy in cancer management. However, this antibody-based technique is limited to detecting a single ...marker per tissue section. Since immunotherapy has revolutionized the antineoplastic therapy, developing new immunohistochemistry strategies to detect multiple markers simultaneously to better understand tumor environment and predict or assess response to immunotherapy is necessary and urgent. Multiplex immunohistochemistry (mIHC)/multiplex immunofluorescence (mIF), such as multiplex chromogenic IHC and multiplex fluorescent immunohistochemistry (mfIHC), is a new and emerging technology to label multiple biomarkers in a single pathological section. The mfIHC shows a higher performance in cancer immunotherapy. This review summarizes the technologies, which are applied for mfIHC, and discusses how they are employed for immunotherapy research.
Near infrared photoimmunotherapy (NIR-PIT) is a newly developed molecular targeted cancer treatment, which selectively kills cancer cells or immune-regulatory cells and induces therapeutic host ...immune responses by administrating a cancer targeting moiety conjugated with IRdye700. The local exposure to near-infrared (NIR) light causes a photo-induced ligand release reaction, which causes damage to the target cell, resulting in immunogenic cell death (ICD) with little or no side effect to the surrounding normal cells. Moreover, NIR-PIT can generate an immune response in distant metastases and inhibit further cancer attack by combing cancer cells targeting NIR-PIT and immune regulatory cells targeting NIR-PIT or other cancer treatment modalities. Several recent improvements in NIR-PIT have been explored such as catheter-driven NIR light delivery, real-time monitoring of cancer, and the development of new target molecule, leading to NIR-PIT being considered as a promising cancer therapy. In this review, we discuss the progress of NIR-PIT, their mechanism and design strategies for cancer treatment. Furthermore, the overall possible targeting molecules for NIR-PIT with their application for cancer treatment are briefly summarised.
Triple-negative breast cancer (TNBC) is a group of heterogeneous and refractory breast cancers with the absence of estrogen receptor (ER), progesterone receptor (PgR) and epidermal growth factor ...receptor 2 (HER2). Over the past decade, antibody drug conjugates (ADCs) have ushered in a new era of targeting therapy. Since the epidermal growth factor receptor (EGFR) and epithelial cell adhesion molecule (EpCAM) are over expressed on triple-negative breast cancer, we developed novel ADCs by conjugating benzylguanine (BG)-modified monomethyl auristatin E (MMAE) to EpCAM- and EGFR-specific SNAP-tagged single chain antibody fragments (scFvs). Rapid and efficient conjugation was achieved by SNAP-tag technology. The binding and internalization properties of scFv-SNAP fusion proteins were confirmed by flow cytometry and fluorescence microscopy. The dose-dependent cytotoxicity was evaluated in cell lines expressing different levels of EGFR and EpCAM. Both ADCs showed specific cytotoxicity to EGFR or EpCAM positive cell lines via inducing apoptosis at a nanomolar concentration. Our study demonstrated that EGFR specific scFv-425-SNAP-BG-MMAE and EpCAM-specific scFv-EpCAM-SNAP-BG-MMAE could be promising ADCs for the treatment of TNBC.
It is widely assumed that the dominant source of scattering in graphene is charged impurities in a substrate. We have tested this conjecture by studying graphene placed on various substrates and in ...high-kappa media. Unexpectedly, we have found no significant changes in carrier mobility either for different substrates or by using glycerol, ethanol, and water as a top dielectric layer. This suggests that Coulomb impurities are not the scattering mechanism that limits the mean free path attainable for graphene on a substrate.
Evolution-inspired engineering of nonribosomal peptide synthetases Bozhüyük, Kenan A J; Präve, Leonard; Kegler, Carsten ...
Science (American Association for the Advancement of Science),
2024-Mar-22, 2024-03-22, 20240322, Letnik:
383, Številka:
6689
Journal Article
Recenzirano
Many clinically used drugs are derived from or inspired by bacterial natural products that often are produced through nonribosomal peptide synthetases (NRPSs), megasynthetases that activate and join ...individual amino acids in an assembly line fashion. In this work, we describe a detailed phylogenetic analysis of several bacterial NRPSs that led to the identification of yet undescribed recombination sites within the thiolation (T) domain that can be used for NRPS engineering. We then developed an evolution-inspired "eXchange Unit between T domains" (XUT) approach, which allows the assembly of NRPS fragments over a broad range of GC contents, protein similarities, and extender unit specificities, as demonstrated for the specific production of a proteasome inhibitor designed and assembled from five different NRPS fragments.
In this study, we investigated the functional role of early growth response-1 (Egr1 gene) in the regulation of radiation-induced clonogenic inhibition and apoptosis in p53 wild-type and mutant ...prostate cancer cells 22Rv1 and DU145, respectively. 22Rv1 cells were more sensitive to irradiation compared with DU145 cells, and the sensitivity was enhanced by overexpression of EGR-1 in both cells. Dominant-negative EGR-1 mutant (dnEGR-1) or repressor of EGR-1, NGFIA binding protein 1 (NAB1), increased radioresistance of these cells. Significant activation of caspases 3 and 9 and Bcl2-associated X (Bax) with increased poly(ADP-ribose) polymerase (PARP) cleavage and cytochrome c release was observed in radiation-exposed EGR-1 overexpressing cells. Gel shift analysis and chloramphenicol acetyl transferase (CAT) reporter assays indicate that EGR-1 transactivates the promoter of the Bax gene. Interaction of EGR-1 and Yes kinase-associated protein 1 (YAP-1) through the WW domain of YAP-1 enhances the transcriptional activity of EGR-1 on the Bax promoter as shown by chromatin immunoprecipitation and reporter assays. Irradiation of PC3 cell xenografts that were treated with adenoviral EGR-1 showed significant regression in tumor volume. These findings establish the radiation-induced pro-apoptotic action of EGR-1, in a p53-independent manner, by directly transactivating Bax, and prove that alters the B-cell CLL/lymphoma 2 (Bcl-2)/Bax ratio as one of the mechanisms resulting in significant activation of caspases, leading to cell death through the novel interaction of EGR-1 with YAP-1.
Quantum-Hall activation gaps in graphene Giesbers, A J M; Zeitler, U; Katsnelson, M I ...
Physical review letters,
11/2007, Letnik:
99, Številka:
20
Journal Article
Recenzirano
Odprti dostop
We have measured the quantum-Hall activation gaps in graphene at filling factors nu=2 and nu=6 for magnetic fields up to 32 T and temperatures from 4 to 300 K. The nu=6 gap can be described by ...thermal excitation to broadened Landau levels with a width of 400 K. In contrast, the gap measured at nu=2 is strongly temperature and field dependent and approaches the expected value for sharp Landau levels for fields B>20 T and temperatures T>100 K. We explain this surprising behavior by a narrowing of the lowest Landau level.
AMPA receptors (AMPAR) are organized into supramolecular complexes in association with other membrane proteins that provide exquisite regulation of their biophysical properties and subcellular ...trafficking. Proline-rich transmembrane protein 1 (PRRT1), also named as SynDIG4, is a component of native AMPAR complexes in multiple brain regions. Deletion of PRRT1 leads to altered surface levels and phosphorylation status of AMPARs, as well as impaired forms of synaptic plasticity. Here, we have investigated the mechanisms underlying the observed regulation of AMPARs by investigating the interaction properties and subcellular localization of PRRT1. Our results show that PRRT1 can interact physically with all AMPAR subunits GluA1-GluA4. We decipher the membrane topology of PRRT1 to find that contrary to the predicted dual membrane pass, only the second hydrophobic segment spans the membrane completely, and is involved in mediating the interaction with AMPARs. We also report a physical interaction of PRRT1 with phosphatase PP2B that dephosphorylates AMPARs during synaptic plasticity. Our co-localization analysis in primary neuronal cultures identifies that PRRT1 associates with AMPARs extrasynaptically where it localizes to early and recycling endosomes as well as to the plasma membrane. These findings advance the understanding of the mechanisms by which PRRT1 regulates AMPARs under basal conditions and during synaptic plasticity.
Graphene is the two-dimensional building block for carbon allotropes of every other dimensionality. Since its experimental discovery, graphene continues to attract enormous interest, in particular as ...a new kind of matter, in which electron transport is governed by a Dirac-like wave equation, and as a model system for studying electronic and phonon properties of other, more complex, graphitic materials1-4. Here, we uncover the constitutive relation of graphene and probe new physics of its optical phonons, by studying its Raman spectrum as a function of uniaxial strain. We find that the doubly degenerate E2g optical mode splits in two components, one polarized along the strain and the other perpendicular to it. This leads to the splitting of the G peak into two bands, which we call G+ and G-, by analogy with the effect of curvature on the nanotube G peak5-7. Both peaks red shift with increasing strain, and their splitting increases, in excellent agreement with first-principles calculations. Their relative intensities are found to depend on light polarization, which provides a useful tool to probe the graphene crystallographic orientation with respect to the strain. The singly degenerate 2D and 2D' bands also red shift, but do not split for small strains. We study the Gruneisen parameters for the phonons responsible for the G, D and D' peaks. These can be used to measure the amount of uniaxial or biaxial strain, providing a fundamental tool for nanoelectronics, where strain monitoring is of paramount importance8, 9
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