Highly Active Mononuclear NAC-Gold(I) Catalysts Blanco Jaimes, Maria Camila; Böhling, Constantin R. N.; Serrano-Becerra, Juan Manuel ...
Angewandte Chemie (International ed.),
July 29, 2013, Letnik:
52, Številka:
31
Journal Article
Recenzirano
One gold is enough: Mononuclear, homogeneous gold catalysts displayed excellent catalytic activity on the order of that previously reported for gold nanoparticle catalysts and surface‐bound gold ...complexes. In the model synthesis of spiro compounds (see picture) extremely high turnover numbers were achieved with only 0.000001 mol % of a silsesquioxane‐substituted catalyst.
Cancer evolution is a complex process influenced by genetic factors and extracellular stimuli that trigger signaling pathways to coordinate the continuous and dynamic interaction between tumor cells ...and the elements of the immune system. For over 20 years now, the immune mechanisms controlling cancer progression have been the focus of intensive research. It is well established that the immune system conveys protective antitumor immunity by destroying immunogenic tumor variants, but also facilitates tumor progression by shaping tumor immunogenicity in a process called “immunoediting”. It is also clear that immune-guided tumor editing is associated with tumor evasion from immune surveillance and therefore reinforcing the endogenous antitumor immunity is a desired goal in the context of cancer therapies. The tumor microenvironment (TME) is a complex network which consists of various cell types and factors having important roles regarding tumor development and progression. Tumor infiltrating lymphocytes (TILs) and other tumor infiltrating immune cells (TIICs) are key to our understanding of tumor immune surveillance based on tumor immunogenicity, whereby the densities and location of TILs and TIICs in the tumor regions, as well as their functional programs (comprising the “immunoscore”) have a prominent role for prognosis and prediction for several cancers. The presence of tertiary lymphoid structures (TLS) in the TME or in peritumoral areas has an influence on the locally produced antitumor immune response, and therefore also has a significant prognostic impact. The cross-talk between elements of the immune system with tumor cells in the TME is greatly influenced by hypoxia, the gut and/or the local microbiota, and several metabolic elements, which, in a dynamic interplay, have a crucial role for tumor cell heterogeneity and reprogramming of immune cells along their activation and differentiation pathways. Taking into consideration the recent clinical success with the application immunotherapies for the treatment of several cancer types, increasing endeavors have been made to gain better insights into the mechanisms underlying phenotypic and metabolic profiles in the context of tumor progression and immunotherapy. In this review we will address (i) the role of TILs, TIICs and TLS in breast cancer (BCa); (ii) the different metabolic-based pathways used by immune and breast cancer cells; and (iii) implications for immunotherapy-based strategies in BCa.
Immune checkpoint inhibitors (ICIs) are in the spotlight of cancer treatment by increasing the probability for long-term survival in patients with metastatic disease and by considerably prolonging ...progression-free survival in patients at early disease stages ....
Tumors and their surrounding area represent spatially organized “ecosystems”, where tumor cells and the immune contextures of the different compartments are in a dynamic interplay, with potential ...clinical impact. Here, we aimed to investigate the prognostic significance of peritumoral tertiary lymphoid structures (TLS) either alone or jointly with the intratumoral densities and spatial distribution of CD8 + and CD163 + cells in breast cancer (BCa) patients. TLS were identified peritumorally, within the area distancing up to 5 mm from the infiltrative tumor border, counted and further characterized as adjacent or distal, in formalin-fixed, paraffin-embedded tumor tissue samples from a cohort of 167 patients, with histologically confirmed invasive ductal BCa. TLS and tumor-infiltrating immune cells were determined by H&E and immunohistochemistry. Clinical follow-up was available for 112 of these patients. Patients with peritumoral TLS exhibited worse disease-free survival (DFS) and overall survival (OS) as compared to patients lacking TLS. Moreover, the density of peritumoral TLS was found to be crucial for prognosis, since patients with abundant TLS exhibited the worst DFS and OS. By combining the density of adjacent TLS (aTLS) with our recently published intratumoral signatures based on the differential distribution of CD8 + and CD163 + in the tumor center and invasive margin, we created two improved immune signatures with superior prognostic strength and higher patient population coverage. Our observations strengthen the notion for the fundamental role of the dynamic interplay between the immune cells within the tumor microenvironment (center/invasive margin) and the tumor surrounding area (peritumoral TLS) on the clinical outcome of BCa patients.
In this investigation IR-change and yellowing of polyurethane as a result of UV radiation were studied. In the presence of UV radiation (200 h,
λ > 300 nm), the synthesized aromatic polyurethane ...undergoes photodegradation with gradual change of its colour. The photochemical degradation of the polyurethane is associated with the scission of the urethane group and photooxidation of the central CH
2 group between the aromatic rings. These reactions are combined with the yellowing of the polyurethane surface. Analysis of the colour changes in PU surface during photodegradation was carried out by measuring CIEL
∗
a
∗
b
∗ colour components (
L
∗,
a
∗,
b
∗ and Δ
E
a
,
b
∗). FT-IR spectroscopy was used to study the chemical changes caused by UV irradiation. The colour difference of yellowing Δ
a
,
b
∗ exhibits a systematic tendency to higher values with increasing irradiation time. Overall, Δ
E
a
,
b
∗ colour change correlates well with photodegradation of polyurethane by relative increase of the concentration of carbonyl group. Our results are in agreement with the quinone (yellow colour) formation as the chromophoric reaction product of polyurethane degradation.
Hepatitis C virus (HCV) uniquely requires the liver-specific microRNA-122 for replication, yet global effects on endogenous miRNA targets during infection are unexplored. Here, high-throughput ...sequencing and crosslinking immunoprecipitation (HITS-CLIP) experiments of human Argonaute (AGO) during HCV infection showed robust AGO binding on the HCV 5′UTR at known and predicted miR-122 sites. On the human transcriptome, we observed reduced AGO binding and functional mRNA de-repression of miR-122 targets during virus infection. This miR-122 “sponge” effect was relieved and redirected to miR-15 targets by swapping the miRNA tropism of the virus. Single-cell expression data from reporters containing miR-122 sites showed significant de-repression during HCV infection depending on expression level and site number. We describe a quantitative mathematical model of HCV-induced miR-122 sequestration and propose that such miR-122 inhibition by HCV RNA may result in global de-repression of host miR-122 targets, providing an environment fertile for the long-term oncogenic potential of HCV.
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•Genome-wide miRNA binding profiles were elucidated for HCV infection•HCV RNA functionally reduces miR-122 binding on endogenous mRNA targets•HCV miRNA sponging can be redirected by swapping viral miRNA tropism•Modeling validates single-cell measurements of HCV-induced mRNA de-repression
Hepatitis C virus uniquely requires the liver-specific tumor suppressor miRNA, miR-122, for its replication. During infection, viral RNA specifically sequesters miR-122 to de-repress its normal host targets, which may facilitate the long-term oncogenic potential of HCV.
The concept of a dual functional programme of the immune system to destroy malignant cells but also to edit their immunogenic profile, considerably improved our understanding of the process of tumor ...evolution in the context of a continuum of interactions between tumor cells and immune lymphocytes. Such an endogenous antitumor immunity throughout the period of cancer development established the concept of cancer immunomodulation which is practically based on a process of selection of more clonal tumors which are manageable by the immune system and constitute the equilibrium phase of immunoediting. The duration of this phase is very important, because the immune system keeps the tumor in a dormant state via cell interactions which establish a balanced state of tumor immunosurveillance versus tumor immune evasion. Depending on the quality and quantity of antitumor immune reactivity and the effectiveness of resistance mechanisms employed by the tumor cells to counteract this immune attack, the equilibrium phase may have shorter or longer duration. Notwithstanding its natural course, the equilibrium phase should be considered as a part of tumor evolutionary process guided by genetic as well as epigenetic changes which in turn activate endogenous cellular immunity to certain levels capable of controlling tumor growth rates and maintain tumor dormancy.
In all known organisms, amino acids are predominantly thought to be synthesized and used as their L-enantiomers. Here, we found that bacteria produce diverse D-amino acids as well, which accumulate ...at millimolar concentrations in supernatants of stationary phase cultures. In Vibrio cholerae, a dedicated racemase produced D-Met and D-Leu, whereas Bacillus subtilis generated D-Tyr and D-Phe. These unusual D-amino acids appear to modulate synthesis of peptidoglycan, a strong and elastic polymer that serves as the stress-bearing component of the bacterial cell wall. D-Amino acids influenced peptidoglycan composition, amount, and strength, both by means of their incorporation into the polymer and by regulating enzymes that synthesize and modify it. Thus, synthesis of D-amino acids may be a common strategy for bacteria to adapt to changing environmental conditions.
The spirochete Borrelia burgdorferi, which causes Lyme disease, has the most segmented genome among known bacteria. In addition to a linear chromosome, the B. burgdorferi genome contains over 20 ...linear and circular endogenous plasmids. While many of these plasmids are dispensable under in vitro culture conditions, they are maintained during the natural life cycle of the pathogen. Plasmid-encoded functions are required for colonization of the tick vector, transmission to the vertebrate host, and evasion of host immune defenses. Different Borrelia strains can vary substantially in the type of plasmids they carry. The gene composition within the same type of plasmid can also differ from strain to strain, impeding the inference of plasmid function from one strain to another. To facilitate the investigation of the role of specific B. burgdorferi plasmids, we developed a Cas9-based approach that targets a plasmid for removal. As a proof-of-principle, we showed that targeting wild-type Cas9 to several loci on the endogenous plasmids lp25 or lp28-1 of the B. burgdorferi type strain B31 results in sgRNA-specific plasmid loss even when homologous sequences (i.e., potential sequence donors for DNA recombination) are present nearby. Cas9 nickase versions, Cas9D10A or Cas9H840A, also cause plasmid loss, though not as robustly. Thus, sgRNA-directed Cas9 DNA cleavage provides a highly efficient way to eliminate B. burgdorferi endogenous plasmids that are non-essential in axenic culture.
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