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A student response system (clickers) was introduced into a second year introductory biochemistry class to improve student engagement and performance. The class was delivered in both internal and distance education (DE) modes, with the DE students receiving recordings of the lectures (including clicker activities). However, there was concern over the use of clickers in internal classes as it may be alienating or distracting to DE students while reviewing the recordings of these lectures. In order to examine students' attitudes toward clickers, closed- and open-ended questions were examined in the student evaluations of teaching (SET). Understanding attitudes of internal and DE students is especially important as differences may exist between these groups due to the different learning environments they experience. Approximately 45% of students completed the surveys, of which 88%-91% provided written comments. Of the written comments, 18% of DE students and 22% of internal students provided unsolicited comments about clickers. Interestingly, no difference was observed in the themes identified in the comments between cohorts. The key themes included 1) clickers were beneficial for learning (and increased knowledge), 2) clickers were engaging/fun, and 3) clickers could have been used more widely. Overall, based on this study, it was believed that clicker usage was not seen as negative activity by DE students and it was worth continuing to use clickers in teaching the large multimodal class studied here. However, there is a need to investigate the potential of new and emerging technologies to provide more interactive experiences for DE students.

Scribble (Scrib) is a highly conserved cell polarity regulator that harbours potent tumour suppressor activity and plays an important role in cell migration. Dysregulation of polarity is associated with poor prognosis during viral infections. Human T‐cell lymphotrophic virus‐1 (HTLV‐1) encodes for the oncogenic Tax1 protein, a modulator of the transcription of viral and human proteins that can cause cell cycle dysregulation as well as a loss of genomic integrity. Previous studies established that Scribble interacts with Tax1 via its C‐terminal PDZ‐binding motif (PBM), leading to aggregation of polarity regulators and subsequent perturbation of host cell adhesion, proliferation, and signalling. Using isothermal titration calorimetry, we now show that all four PDZ domains of Scribble bind to Tax1 PBM. We then determined crystal structures of Scribble PDZ1, PDZ2 and PDZ3 domains bound to Tax1 PBM. Our findings establish a structural basis for Tax1‐mediated subversion of Scribble‐mediated cell polarity signalling and provide the platform for mechanistic studies to examine Tax1 induced mislocalization of Scribble and the associated changes in cellular architecture and subsequent tumorigenesis. [ABSTRACT FROM AUTHOR]

We recently reported that the membrane‐associated progesterone receptor (MAPR) protein family (mammalian members: PGRMC1, PGRMC2, NEUFC and NENF) originated from a new class of prokaryotic cytochrome b5 (cytb5) domain proteins, called cytb5M (MAPR‐like). Relative to classical cytb5 proteins, MAPR and ctyb5M proteins shared unique sequence elements and a distinct heme‐binding orientation at an approximately 90° rotation relative to classical cytb5, as demonstrated in the archetypal crystal structure of a cytb5M protein (PDB accession number 6NZX). Here, we present the crystal structure of an archaeal cytb5M domain (Methanococcoides burtoniiWP_011499504.1, PDB:6VZ6). It exhibits similar heme binding to the 6NZX cytb5M, supporting the deduction that MAPR‐like heme orientation was inherited from the prokaryotic ancestor of the original eukaryotic MAPR gene. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is one of the leading causes of nosocomial infections, accounting for 10% of all hospital‐acquired infections. Current antibiotics against P. aeruginosa are becoming increasingly ineffective due to the exponential rise in drug resistance. Thus, there is an urgent need to validate and characterize novel drug targets to guide the development of new classes of antibiotics against this pathogen. One such target is the diaminopimelate (DAP) pathway, which is responsible for the biosynthesis of bacterial cell wall and protein building blocks, namely meso‐DAP and lysine. The rate‐limiting step of this pathway is catalysed by the enzyme dihydrodipicolinate synthase (DHDPS), typically encoded for in bacteria by a single dapA gene. Here, we show that P. aeruginosa encodes two functional DHDPS enzymes, PaDHDPS1 and PaDHDPS2. Although these isoforms have similar catalytic activities (kcat = 29 s−1 and 44 s−1 for PaDHDPS1 and PaDHDPS2, respectively), they are differentially allosterically regulated by lysine, with only PaDHDPS2 showing inhibition by the end product of the DAP pathway (IC50 = 130 μm). The differences in allostery are attributed to a single amino acid difference in the allosteric binding pocket at position 56. This is the first example of a bacterium that contains multiple bona fide DHDPS enzymes, which differ in allosteric regulation. We speculate that the presence of the two isoforms allows an increase in the metabolic flux through the DAP pathway when required in this clinically important pathogen. Databases: PDB ID: 6P90. [ABSTRACT FROM AUTHOR]

The boom in growth of 1,4‐disubstituted triazole products, in particular, since the early 2000's, can be largely attributed to the birth of click chemistry and the discovery of the CuI‐catalyzed azide–alkyne cycloaddition (CuAAC). Yet the synthesis of relatively simple, albeit important, 1‐substituted‐1,2,3‐triazoles has been surprisingly more challenging. Reported here is a straightforward and scalable click‐inspired protocol for the synthesis of 1‐substituted‐1,2,3‐triazoles from organic azides and the bench stable acetylene surrogate ethenesulfonyl fluoride (ESF). The new transformation tolerates a wide selection of substrates and proceeds smoothly under metal‐free conditions to give the products in excellent yield. Under controlled acidic conditions, the 1‐substituted‐1,2,3‐triazole products undergo a Michael addition reaction with a second equivalent of ESF to give the unprecedented 1‐substituted triazolium sulfonyl fluoride salts. [ABSTRACT FROM AUTHOR]