From Sensors to Silencers: Quinoline- and Benzimidazole-Sulfonamides as Inhibitors for Zinc Proteases

Derived from the extensive work in the area of small molecule zinc(II) ion sensors, chelating fragment libraries of quinoline- and benzimidazole-sulfonamides have been prepared and screened against several different zinc(II)-dependent matrix metalloproteinases (MMPs). The fragments show impressive inhibition of these metalloenzymes and preferences for different MMPs based on the nature of the chelating group. The findings show that focused chelator libraries are a powerful strategy for the discovery of lead fragments for metalloprotein inhibition

Selective G-Quadruplex DNA Recognition by a New Class of Designed Cyanines

A variety of cyanines provide versatile and sensitive agents acting as DNA stains and sensors and have been structurally modified to bind in the DNA minor groove in a sequence dependent manner. Similarly, we are developing a new set of cyanines that have been designed to achieve highly selective binding to DNA G-quadruplexes with much weaker binding to DNA duplexes. A systematic set of structurally analogous trimethine cyanines has been synthesized and evaluated for quadruplex targeting. The results reveal that elevated quadruplex binding and specificity are highly sensitive to the polymethine chain length, heterocyclic structure and intrinsic charge of the compound. Biophysical experiments show that the compounds display significant selectivity for quadruplex binding with a higher preference for parallel stranded quadruplexes, such as cMYC. NMR studies revealed the primary binding through an end-stacking mode and SPR studies showed the strongest compounds have primary KD values below 100 nM that are nearly 100-fold weaker for duplexes. The high selectivity of these newly designed trimethine cyanines for quadruplexes as well as their ability to discriminate between different quadruplexes are extremely promising features to develop them as novel probes for targeting quadruplexes in vivo

Variations in Implementation of Specifications Grading in STEM Courses

Specifications grading is an assessment strategy based on mastery learning, clear learning objectives, and frequent evaluations and feedback. Twelve instructors at a southeastern four-year public college implemented the specifications grading method across eight discrete courses in four STEM areas. In this modified assessment strategy, the students controlled their grades through multiple attempts, with limitations, on assessments of course objectives. The instructors designed and executed specifications grading in unique ways that aligned with their content areas, teaching beliefs, and individual teaching styles. Preliminary observations suggest that, regardless of subject area, specifications grading can be used as an alternative to traditional assessment methodologies in STEM courses, regardless of the content area. In general, three major variations of implementation arose from this initial trial. Major differences and commonalities among these types are discussed as they relate to the course subject area in which they are used. The results of this work add a unique set of assessment practices to the current body of knowledge in that other practitioners may gain insight on variations of the specifications grading method that may be practical and applicable in their own classrooms

2-{(E)-2-[(3E)-2-Chloro-3-{(2E)-2-[1,1-dimethyl-3-(3-phenylpropyl)-1,3-dihydro-2H-benzo[e]indol-2-ylidene]-ethylidene}cyclohex-1-en-1-yl]ethenyl}-1,1-dimethyl-3-(3-phenylpropyl)-1H-benzo[e]indolium Iodide

In four synthetic steps we successfully prepared a red-shifted heptamethine cyanine dye (λmax = 825 nm in methanol) that could be very useful for biochemists and bioanalytical chemists for probing lipophilic environments, including the hydrophobic pockets of enzymes. The heptamethine dye structure was characterized by various spectroscopic techniques including 1H-NMR, 13C-NMR and high-resolution accurate mass spectroscopy (HRMS). We have also shown the hydrophobicity spectrally by varying methanol/water ratios and observing corresponding absorbance and fluorescence spectral changes

Child car restraints: Mandating type and seating row according to age with positive effect in regional city in Queensland, Australia

Road trauma is a leading cause of child injury worldwide. In highly motorised countries, injury as a passenger represents a major proportion of all child road deaths and hospitalisations. Australia is no exception, particularly since there are high levels of private motor vehicle travel to school in most Australian states. Recently the legislation governing the type of car restraints required for children aged under 7 years has changed in Australia, aligning requirements better with accepted best practice. However, it is unclear what effect these changes have had on children’s seating positions or the types of restraints used. A mixed methods evaluation of the impact of the new legislation on compliance was conducted at three times: baseline (Time 1); after announcement that changes were going to be implemented but before enforcement began (Time 2); and after enforcement commenced (Time 3). Measures of compliance were obtained using two methods: road-side observations of vehicles with child passengers; and parental self-report (intercept interviews conducted at Time 2 and Time 3 only). Results from the observations suggested an overall positive effect. Proportions of children occupying front seats decreased overall and use of dedicated child seats increased to almost 40% of the observed children by Time 3. However, almost a quarter of the children observed still occupied front seats. These results differed from those of the interview study where almost no children were reported as usually travelling in the front seat, and reported use of dedicated restraints with children was almost 90%, over twice that of the observations

Structure-inherent targeting of near-infrared fluorophores for parathyroid and thyroid gland imaging

Surgical oncolog