A General Synthesis of C8-Arylpurine Phosphoramidites

A general scheme for the synthesis of C8-arylpurine phosphoramidites has been developed. C8-Arylation of C8-bromo-2′-deoxyguanosine is the key step and has been achieved through the use of a Suzuki coupling. Since the coupling reaction is conducted under aqueous conditions, it is unnecessary to protect and then deprotect the hydroxyl groups, thus saving several steps and improving overall yields. Once the C8-arylgroup is introduced, the glycosidic bond becomes very sensitive to acid catalyzed cleavage. Protection of the amino groups as the corresponding N,N-dimethylformamidine derivative improves stability of the derivatives. Synthetic C8-arylpurines were successfully used to prepare synthetic oligonucleotides

A General Synthesis of C8-Arylpurine Phosphoramidite

A general scheme for the synthesis of C8-arylpurine phosphoramidites has been developed. C8-Arylation of C8-bromo-2′-deoxyguanosine is the key step and has been achieved through the use of a Suzuki coupling. Since the coupling reaction is conducted under aqueous conditions, it is unnecessary to protect and then deprotect the hydroxyl groups, thus saving several steps and improving overall yields. Once the C8-arylgroup is introduced, the glycosidic bond becomes very sensitive to acid catalyzed cleavage. Protection of the amino groups as the corresponding N,N-dimethylformamidine derivative improves stability of the derivatives. Synthetic C8-arylpurines were successfully used to prepare synthetic oligonucleotides

Multiply Folded Graphene

The folding of paper, hide, and woven fabric has been used for millennia to achieve enhanced articulation, curvature, and visual appeal for intrinsically flat, two-dimensional materials. For graphene, an ideal two-dimensional material, folding may transform it to complex shapes with new and distinct properties. Here, we present experimental results that folded structures in graphene, termed grafold, exist, and their formations can be controlled by introducing anisotropic surface curvature during graphene synthesis or transfer processes. Using pseudopotential-density functional theory calculations, we also show that double folding modifies the electronic band structure of graphene. Furthermore, we demonstrate the intercalation of C60 into the grafolds. Intercalation or functionalization of the chemically reactive folds further expands grafold's mechanical, chemical, optical, and electronic diversity.Comment: 29 pages, 10 figures (accepted in Phys. Rev. B

An investigation into the feasibility of myoglobin-based single-electron transistors

Myoglobin single-electron transistors were investigated using nanometer- gap platinum electrodes fabricated by electromigration at cryogenic temperatures. Apomyoglobin (myoglobin without heme group) was used as a reference. The results suggest single electron transport is mediated by resonant tunneling with the electronic and vibrational levels of the heme group in a single protein. They also represent a proof-of-principle that proteins with redox centers across nanometer-gap electrodes can be utilized to fabricate single-electron transistors. The protein orientation and conformation may significantly affect the conductance of these devices. Future improvements in device reproducibility and yield will require control of these factors

Are school-level factors associated with primary school students' experience of physical violence from school staff in Uganda?

BACKGROUND: The nature and structure of the school environment has the potential to shape children's health and well being. Few studies have explored the importance of school-level factors in explaining a child's likelihood of experiencing violence from school staff, particularly in low-resource settings such as Uganda. METHODS: To quantify to what extent a student's risk of violence is determined by school-level factors we fitted multilevel logistic regression models to investigate associations and present between-school variance partition coefficients. School structural factors, academic and supportive environment are explored. RESULTS: 53% of students reported physical violence from staff. Only 6% of variation in students' experience of violence was due to differences between schools and half the variation was explained by the school-level factors modelled. Schools with a higher proportion of girls are associated with increased odds of physical violence from staff. Students in schools with a high level of student perceptions of school connectedness have a 36% reduced odds of experiencing physical violence from staff, but no other school-level factor was significantly associated. CONCLUSION: Our findings suggest that physical violence by school staff is widespread across different types of schools in this setting, but interventions that improve students' school connectedness should be considered

Selection of Single-Stranded DNA Molecular Recognition Elements against Exotoxin A Using a Novel Decoy-SELEX Method and Sensitive Detection of Exotoxin A in Human Serum

Exotoxin A is one of the virulence factors of Pseudomonas aeruginosa, a bacterium that can cause infections resulting in adverse health outcomes and increased burden to health care systems. Current methods of diagnosing P. aeruginosa infections are time consuming and can require significant preparation of patient samples. This study utilized a novel variation of the Systematic Evolution of Ligand by Exponential Enrichment, Decoy-SELEX, to identify an Exotoxin A specific single-stranded DNA (ssDNA) molecular recognition element (MRE). Its emphasis is on increasing stringency in directing binding toward free target of interest and at the same time decreasing binding toward negative targets. A ssDNA MRE with specificity and affinity was identified after fourteen rounds of Decoy-SELEX. Utilizing surface plasmon resonance measurements, the determined equilibrium dissociation constant of the MRE is between 4.2 µM and 4.5 µM, and is highly selective for Exotoxin A over negative targets. A ssDNA MRE modified sandwich enzyme-linked immunosorbent assay (ELISA) has been developed and achieved sensitive detection of Exotoxin A at nanomolar concentrations in human serum. This study has demonstrated the proof-of-principle of using a ssDNA MRE as a clinical diagnostic tool

Selection of Single-Stranded DNA Molecular Recognition Elements against Exotoxin A Using a Novel Decoy-SELEX Method and Sensitive Detection of Exotoxin A in Human Serum

Exotoxin A is one of the virulence factors of Pseudomonas aeruginosa, a bacterium that can cause infections resulting in adverse health outcomes and increased burden to health care systems. Current methods of diagnosing P. aeruginosa infections are time consuming and can require significant preparation of patient samples. This study utilized a novel variation of the Systematic Evolution of Ligand by Exponential Enrichment, Decoy-SELEX, to identify an Exotoxin A specific single-stranded DNA (ssDNA) molecular recognition element (MRE). Its emphasis is on increasing stringency in directing binding toward free target of interest and at the same time decreasing binding toward negative targets. A ssDNA MRE with specificity and affinity was identified after fourteen rounds of Decoy-SELEX. Utilizing surface plasmon resonance measurements, the determined equilibrium dissociation constant of the MRE is between 4.2 µM and 4.5 µM, and is highly selective for Exotoxin A over negative targets. A ssDNA MRE modified sandwich enzyme-linked immunosorbent assay (ELISA) has been developed and achieved sensitive detection of Exotoxin A at nanomolar concentrations in human serum. This study has demonstrated the proof-of-principle of using a ssDNA MRE as a clinical diagnostic tool

Src Binds Cortactin Through An Sh2 Domain Cystine-Mediated Linkage

Tyrosine-kinase-based signal transduction mediated by modular protein domains is critical for cellular function. The Src homology (SH)2 domain is an important conductor of intracellular signaling that binds to phosphorylated tyrosines on acceptor proteins, producing molecular complexes responsible for signal relay. Cortactin is a cytoskeletal protein and tyrosine kinase substrate that regulates actin-based motility through interactions with SH2-domain-containing proteins. The Src kinase SH2 domain mediates cortactin binding and tyrosine phosphorylation, but how Src interacts with cortactin is unknown. Here we demonstrate that Src binds cortactin through cystine bonding between Src C185 in the SH2 domain within the phosphotyrosine binding pocket and cortactin C112/246 in the cortactin repeats domain, independent of tyrosine phosphorylation. Interaction studies show that the presence of reducing agents ablates Src-cortactin binding, eliminates cortactin phosphorylation by Src, and prevents Src SH2 domain binding to cortactin. Tandem MS/MS sequencing demonstrates cystine bond formation between Src C185 and cortactin C112/246. Mutational studies indicate that an intact cystine binding interface is required for Src-mediated cortactin phosphorylation, cell migration, and pre-invadopodia formation. Our results identify a novel phosphotyrosine-independent binding mode between the Src SH2 domain and cortactin. Besides Src, one quarter of all SH2 domains contain cysteines at or near the analogous Src C185 position. This provides a potential alternative mechanism to tyrosine phosphorylation for cysteine-containing SH2 domains to bind cognate ligands that may be widespread in propagating signals regulating diverse cellular functions

Development of Healthy Eating and Physical Activity Quality Standards for Out-of-School Time Programs

Abstract Background: Out-of-school time (Ost) programs serve over 8 million children per year and have ample opportunity to promote health through menu and physical activity choices. Until recently, however, the field has lacked a comprehensive set of operationalizable standards for healthy eating and physical activity. the National Afterschool Association adopted voluntary healthy eating and physical activity quality standards (HePAQs) in April, 2011. Methods: We describe the development of HePAQs. this work reflects a social ecological model for changing children's eating and activity behaviors through program-level interventions. the standards were developed using a national, mixed-methods needs assessment, review of existing standards and expert recommendations, and a participatory process of discussion, review, and consensus engaging 19 influential service and policy organizations and agencies in the Healthy Out-of-school time (HOst) coalition, which we convened in 2009. Results: the HOst coalition approved a final version of the HePAQs in January, 2011. the 11 standards address content, curriculum selection, staff training, program support, and environmental support for healthy eating and physical activity. in April, 2011, the HePAQs were adopted by the National Afterschool Association, and have subsequently been widely disseminated. extensive adoption and implementation efforts are underway. Conclusions: the availability of a comprehensive set of standards for healthy eating and physical activity in Ost provides practical information to help community-based youth-serving organizations participate in obesity and chronic disease prevention. A working awareness of their content will be useful to scientists undertaking health promotion studies in the out-of-school time setting

Application of Hansch’s Model to Capsaicinoids and Capsinoids: A Study Using the Quantitative Structure−Activity Relationship. A Novel Method for the Synthesis of Capsinoids

We describe a synthetic approach for two families of compounds, the capsaicinoids and capsinoids, as part of a study of the quantitative relationship between structure and activity