6-Benzyl-3,4-dimeth­oxy-10-methyl­pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolin-5(6H)-one

Pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolin-5(6H)-ones such as the title compound, C24H21N3O3, can be obtained in a few minutes in a microwave-assisted three-component reaction from 2-amino­pyridines, isocyanides and 2-carboxy­benz­aldehydes. In the title compound, the pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolin-5(6H)-one ring system is almost planar (mean deviation 0.068 Å). The dihedral angle between the benzyl ring and the pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolin-5(6H)-one ring system is 78.2°. The crystal structure is stabilized by inter­molecular C—H⋯O and C—H⋯N hydrogen bonds

Synthesis of New Methano[1,5]dioxocines via a Domino Reaction of 4-Hydroxy-2H-pyran-2-ones / 4-Hydroxy-2H-chromen-2-ones with Acyclic 1,3-Diketones

New methan

Abriendo Puertas Expansion Management Model

Abriendo Puertas is a small, education non-profit using parental engagement initiatives to reduce the number of Hispanic student dropouts in Texas. To date, Abriendo Puertas has seen much success - both in recognition by external organizations and in the wide support of its parent participants and volunteers. As such, Abriendo Puertas hopes to expand its program across the state, most notably to the Fort Worth area. The nonprofit is interested in solidifying its current operations in the hope of expanding its impact.Building upon previous research, an Expansion Management Model (EMM) was produced to guide Abriendo Puertas' efforts. Combining research-based best practices, an analysis of the nonprofit's current practices (based primarily on an internal assessment), and a survey of the parents involved with Abriendo Puertas, the EMM includes tailored recommendations to Abriendo Puertas' needs. The Capstone team made four key recommendations: 1. Solidify the organization's mission; 2. Expand and diversify the board of directors; Complete a strategic marketing plan; and Develop a database to track the organization's parent participants and volunteers. The Capstone report includes the final Expansion Management Model, complete with a full set of recommendations, a description of the Assessment Tool and Survey, as well as a demographic analysis identifying possible expansion points within the state of Texas

Reactions of Azides with Electrophiles: New Methods for the Generation of Cationic 2‐Azabutadienes. Synthesis of 1,2, 3,4‐Tetrahydroquinolines and 1,2‐Dihydroquinolines via a Hetero Diels–Alder Reaction

Two methods for the generation of iminium ions of the type ArN + (X)=CHR (X = H or alkyl, R = H or alkyl) are reported: (1) the Bronsted‐acid‐promoted rearrangement of benzylic azides and (2) the intermolecular Schmidt reactions of azides XN 3 (X = aliphatic) with benzylic carbocations derived from benzylic alcohols ArCH(R)OH. The iminium ions ArN + (X)=CHR behave as cationic 2‐azabutadienes in the presence of alkenes and alkynes, producing 1,2, 3,4‐tetrahydroquinolines and 1,2‐dihydroquinolines by a hetero Diels–Alder reaction.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101768/1/199700007_ftp.pd

SHANK proteins limit integrin activation by directly interacting with Rap1 and R-Ras

SHANK3, a synaptic scaffold protein and actin regulator, is widely expressed outside of the central nervous system with predominantly unknown function. Solving the structure of the SHANK3 N-terminal region revealed that the SPN domain is an unexpected Ras-association domain with high affinity for GTP-bound Ras and Rap G-proteins. The role of Rap1 in integrin activation is well established but the mechanisms to antagonize it remain largely unknown. Here, we show that SHANK1 and SHANK3 act as integrin activation inhibitors by sequestering active Rap1 and R-Ras via the SPN domain and thus limiting their bioavailability at the plasma membrane. Consistently, SHANK3 silencing triggers increased plasma membrane Rap1 activity, cell spreading, migration and invasion. Autism-related mutations within the SHANK3 SPN domain (R12C and L68P) disrupt G-protein interaction and fail to counteract integrin activation along the Rap1-RIAM-talin axis in cancer cells and neurons. Altogether, we establish SHANKs as critical regulators of G-protein signalling and integrin-dependent processes