scholarly journals A more critical role for silicon in the catalytic Staudinger amidation: silanes as non-innocent reductants

2017 ◽  
Vol 53 (57) ◽  
pp. 7982-7985 ◽  
Author(s):  
Keith G. Andrews ◽  
Ross M. Denton

We demonstrate that in situ-generated silyl ester intermediates are key mediators of the catalytic, traceless Staudinger amidation reaction.


2006 ◽  
Vol 291 (6) ◽  
pp. F1123-F1132 ◽  
Author(s):  
James J. De Yoreo ◽  
S. Roger Qiu ◽  
John R. Hoyer

Calcium oxalate monohydrate (COM) is the primary constituent of the majority of renal stones. Osteopontin (OPN), an aspartic acid-rich urinary protein, and citrate, a much smaller molecule, are potent inhibitors of COM crystallization at levels present in normal urine. Current concepts of the role of site-specific interactions in crystallization derived from studies of biomineralization are reviewed to provide a context for understanding modulation of COM growth at a molecular level. Results from in situ atomic force microscopy (AFM) analyses of the effects of citrate and OPN on growth verified the critical role of site-specific interactions between these growth modulators and individual steps on COM crystal surfaces. Molecular modeling investigations of interactions of citrate with steps and faces on COM crystal surfaces provided links between the stereochemistry of interaction and the binding energy levels that underlie mechanisms of growth modification and changes in overall crystal morphology. The combination of in situ AFM and molecular modeling provides new knowledge that will aid rationale design of therapeutic agents for inhibition of stone formation.



2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Chenrayan Senthil ◽  
Sun-Sik Kim ◽  
Hyun Young Jung

AbstractPolymer binders for sulfur cathodes play a very critical role as they prerequisites for an in-situ immobilization against polysulfide shuttle and volume change, while ensuring good adhesion within active materials for ion conduction along with robust mechanical and chemical stability. Here, we demonstrate anionic surface charge facilitated bio-polymer binder for sulfur cathodes enabling excellent performance and fire safety improvement. The aqueous-processable tragacanth gum-based binder is adjusted to house high sulfur loading over 12 mg cm−2 without compromising the sulfur utility and reversibility, imparting high accessibility for Li-ions to sulfur particles about 80%. The intrinsic rod and sphere-like saccharidic conformal fraction’s multifunctional polar units act as active channels to reach the sulfur particles. As a result, the binder entraps polysulfides with 46% improvement and restrains the volume changes within 16 % even at 4 C. Moreover, the flexible Li-S battery delivers a stack gravimetric energy density of 243 Wh kg–1, demonstrating high reactivity of sulfur along with good shape conformality, which would open an avenue for the potential development of the compact and flexible high-power device.



Nano Letters ◽  
2018 ◽  
Vol 18 (4) ◽  
pp. 2595-2602 ◽  
Author(s):  
Alejandro Barrios ◽  
Saurabh Gupta ◽  
Gustavo M. Castelluccio ◽  
Olivier N. Pierron


Author(s):  
Xiaomeng Guo ◽  
Hongbo Chen ◽  
Yan Liu ◽  
Dawei Yang ◽  
Qian Li ◽  
...  

Emerging studies have shown that mitochondrial G-quadruplex plays a critical role in regulating mitochondrial gene replication and transcription, which makes it a promising target for the diagnosis and treatment of...



Eureka ◽  
2010 ◽  
Vol 1 (1) ◽  
pp. 11-19
Author(s):  
Braden Teitge

Retinoic acid signalling plays a critical role during zebrafish development.  The teratogenic effects of retinoic acid have been demonstrated by embryonic deformation resulting from insufficient or excessive levels of this vitamin A derivative.  During embryogenesis, bone morphogenetic proteins are closely linked to the physiological interpretation of RA gradients, particularly in the hindbrain.  We describe an uncharacterized gene, Bmpr1bb, as being significantly downregulated in response to retinoic acid treatment.  In situ expression demonstrates that Bmpr1bb is expressed ubiquitously at 10hpf, and is slowly downregulated until 48hpf where the expression is concentrated in the hindbrain.  We propose that Bmpr1bb is a downstream target of RA signalling, strongly downregulated during embryogenesis and specified to a specific region of the hindbrain.



2019 ◽  
Vol 93 (17) ◽  
Author(s):  
Yaoyao Zhang ◽  
Na Tang ◽  
Jun Luo ◽  
Man Teng ◽  
Katy Moffat ◽  
...  

ABSTRACT MicroRNAs (miRNAs) are small noncoding RNAs with profound regulatory roles in many areas of biology, including cancer. MicroRNA 155 (miR-155), one of the extensively studied multifunctional miRNAs, is important in several human malignancies such as diffuse large B cell lymphoma and chronic lymphocytic leukemia. Moreover, miR-155 orthologs KSHV-miR-K12-11 and MDV-miR-M4, encoded by Kaposi’s sarcoma-associated herpesvirus (KSHV) and Marek’s disease virus (MDV), respectively, are also involved in oncogenesis. In MDV-induced T-cell lymphomas and in lymphoblastoid cell lines derived from them, MDV-miR-M4 is highly expressed. Using excellent disease models of infection in natural avian hosts, we showed previously that MDV-miR-M4 is critical for the induction of T-cell lymphomas as mutant viruses with precise deletions were significantly compromised in their oncogenicity. However, those studies did not elucidate whether continued expression of MDV-miR-M4 is essential for maintaining the transformed phenotype of tumor cells. Here using an in situ CRISPR/Cas9 editing approach, we deleted MDV-miR-M4 from the MDV-induced lymphoma-derived lymphoblastoid cell line MDCC-HP8. Precise deletion of MDV-miR-M4 was confirmed by PCR, sequencing, quantitative reverse transcription-PCR (qRT-PCR), and functional analysis. Continued proliferation of the MDV-miR-M4-deleted cell lines demonstrated that MDV-miR-M4 expression is not essential for maintaining the transformed phenotype, despite its initial critical role in the induction of lymphomas. Ability to examine the direct role of oncogenic miRNAs in situ in tumor cell lines is valuable in delineating distinct determinants and pathways associated with the induction or maintenance of transformation in cancer cells and will also contribute significantly to gaining further insights into the biology of oncogenic herpesviruses. IMPORTANCE Marek’s disease virus (MDV) is an alphaherpesvirus associated with Marek’s disease (MD), a highly contagious neoplastic disease of chickens. MD serves as an excellent model for studying virus-induced T-cell lymphomas in the natural chicken hosts. Among the limited set of genes associated with MD oncogenicity, MDV-miR-M4, a highly expressed viral ortholog of the oncogenic miR-155, has received extensive attention due to its direct role in the induction of lymphomas. Using a targeted CRISPR-Cas9-based gene editing approach in MDV-transformed lymphoblastoid cell lines, we show that MDV-miR-M4, despite its critical role in the induction of tumors, is not essential for maintaining the transformed phenotype and continuous proliferation. As far as we know, this was the first study in which precise editing of an oncogenic miRNA was carried out in situ in MD lymphoma-derived cell lines to demonstrate that it is not essential in maintaining the transformed phenotype.



2017 ◽  
Vol 15 (30) ◽  
pp. 6426-6432 ◽  
Author(s):  
Daan F. J. Hamstra ◽  
Danny C. Lenstra ◽  
Tjeu J. Koenders ◽  
Floris P. J. T. Rutjes ◽  
Jasmin Mecinović

In situ reduction of phosphine oxide by poly(methylhydrosiloxane) leads to efficient amidation reaction between carboxylic acids and amines.



Viruses ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 434
Author(s):  
Seyedeh Raheleh Niavarani ◽  
Christine Lawson ◽  
Lee-Hwa Tai

Oncolytic viruses (OVs) are a form of immunotherapy that release tumor antigens in the context of highly immunogenic viral signals following tumor-targeted infection and destruction. Emerging preclinical and clinical evidence suggests that this in situ vaccine effect is critical for successful viro-immunotherapy. In this review, we discuss the application of OV as an infected cell vaccine (ICV) as one method of enhancing the potency and breadth of anti-tumoral immunity. We focus on understanding and manipulating the critical role of natural killer (NK) cells and their interactions with other immune cells to promote a clinical outcome. With a synergistic tumor killing and immune activating mechanism, ICVs represent a valuable new addition to the cancer fighting toolbox with the potential to treat malignant disease.



2007 ◽  
Vol 103 (1) ◽  
pp. 220-227 ◽  
Author(s):  
Veronica A. L. Toppin ◽  
Michael B. Harris ◽  
Anna M. Kober ◽  
J. C. Leiter ◽  
Walter M. St.-John

In severe hypoxia or ischemia, normal eupneic breathing is replaced by gasping, which can serve as a powerful mechanism for “autoresuscitation.” We have proposed that gasping is generated by medullary neurons having intrinsic pacemaker bursting properties dependent on a persistent sodium current. A number of neuromodulators, including serotonin, influence persistent sodium currents. Thus we hypothesized that endogenous serotonin is essential for gasping to be generated. To assess such a critical role for serotonin, a preparation of the perfused, juvenile in situ rat was used. Activities of the phrenic, hypoglossal, and vagal nerves were recorded. We added blockers of type 1 and/or type 2 classes of serotonergic receptors to the perfusate delivered to the preparation. Eupnea continued following additions of any of the blockers. Changes were limited to an increase in the frequency of phrenic bursts and a decline in peak heights of all neural activities. In ischemia, gasping was induced following any of the blockers. Few statistically significant changes in parameters of gasping were found. We thus did not find a differential suppression of gasping, compared with eupnea, following blockers of serotonin receptors. Such a differential suppression had been proposed based on findings using an in vitro preparation. We hypothesize that multiple neurotransmitters/neuromodulators influence medullary mechanisms underlying the neurogenesis of gasping. In greatly reduced in vitro preparations, the importance of any individual neuromodulator, such as serotonin, may be exaggerated compared with its role in more intact preparations.



2005 ◽  
Vol 288 (5) ◽  
pp. G933-G942 ◽  
Author(s):  
Rabii Ameziane El Hassani ◽  
Nesrine Benfares ◽  
Bernard Caillou ◽  
Monique Talbot ◽  
Jean-Christophe Sabourin ◽  
...  

The dual oxidase (Duox)2 flavoprotein is strongly expressed in the thyroid gland, where it plays a critical role in the synthesis of thyroid hormones by providing thyroperoxidase with H2O2. DUOX2 mRNA was recently detected by RT-PCR and in-situ hybridization experiments in other tissues, such as rat colon and rat and human epithelial cells from the salivary excretory ducts and rectal glands. We examined Duox2 expression at the protein level throughout the porcine digestive tract and in human colon. Western blot analysis identified Duox2 as the same two molecular species ( Mr 165 and 175 kDa) as detected in the thyroid. It was expressed in all the tissues tested, but the highest levels were found in the cecum and sigmoidal colon. Immunohistochemical studies showed that Duox2 protein is mainly present in these parts of the gut and located at the apical membrane of the enterocytes in the brush border, indicating that it is expressed only in highly differentiated cells. A Ca2+/NADPH-dependent H2O2-generating system was associated with Duox2 protein expression, which had the same biochemical characteristics as the NADPH oxidase in the thyroid. Indeed, treatment of the thyroid and cecum particulate fractions with phenylarsine oxide resulted in complete calcium desensitization of both enzymes. A marked increase in DUOX2 expression was also found during spontaneous differentiation of postconfluent Caco-2 cells. The discovery of Duox2 as a novel source of H2O2 in the digestive tract, particularly in the cecum and colon, makes it a new candidate mediator of physiopathological processes.



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