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Type 2 transglutaminase (TG2) is an important cancer stem cell survival protein that exists in open and closed conformations. The major intracellular form is the closed conformation that functions as a GTP-binding GTPase and is required for cancer stem cell survival. However, at a finite rate, TG2 transitions to an open conformation that exposes the transamidase catalytic site involved in protein–protein crosslinking. The activities are mutually exclusive, as the closed conformation has GTP binding/GTPase activity, and the open conformation transamidase activity. We recently showed that GTP binding, but not transamidase activity, is required for TG2-dependent cancer stem cell invasion, migration and tumour formation. However, we were surprised that transamidase site-specific inhibitors reduce cancer stem cell survival. We now show that compounds NC9, VA4 and VA5, which react exclusively at the TG2 transamidase site, inhibit both transamidase and GTP-binding activities. Transamidase activity is inhibited by direct inhibitor binding at the transamidase site, and GTP binding is blocked because inhibitor interaction at the transamidase site locks the protein in the extended/open conformation to disorganize/inactivate the GTP binding/GTPase site. These findings suggest that transamidase site-specific inhibitors can inhibit GTP binding/signalling by driving a conformation change that disorganizes the TG2 GTP binding to reduce TG2-dependent signalling, and that drugs designed to target this site may be potent anti-cancer agents.

A Correction to this paper has been published: https://doi.org/10.1038/s41388-021-01709-5

A new group of error-prone DNA polymerases overcomes the blockage posed to normal DNA replication by damaged template bases, suggesting an active site with a loose, flexible pocket that accommodates aberrant DNA structures. We have determined a 2.8 Å resolution crystal structure of the Sulfolobus solfataricus Dbh protein, a DNA translesion polymerase closely related to Escherichia coli DNA polymerase IV and human polymerase κ. A high error rate is observed for the Dbh polymerase in a range of 10 −2 –10 −3 for all 12 base substitution mispairs. The crystal structure of Dbh reveals an overall architecture resembling other DNA polymerases but has unique features that are likely to contribute to error-prone synthesis, including −1 frameshifting mutations.

Records of 244 patients with Mycobacterium kansasii isolated from their sputum were reviewed. Of the 244 patients, 82 failed to meet study criteria and were excluded. Response to treatment and posttreatment follow-up was evaluated in 162 patients. Overall, 135 patients (83%) achieved negative sputum cultures within six months. Among 32 patients whose drug regimen included rifampin, all 32 (100%) had negative cultures at the fourth and fifth months, but two relapsed during the sixth month, with cultures resistant to 1.0 and 25 μg of rifampin/ml. Among 130 patients whose regimen did not include rifampin, negative sputum cultures were achieved by the sixth month in 101 (80%). In these patients, no significant influence could be attributed to (1) the use of three-drug vs. two-drug regimens; (2) the in vitro susceptibility of pretreatment cultures to isoniazid; (3) the coexistence of obstructive airway disease; or (4) the early use of pulmonary resection. The susceptibility of pretreatment cultures to streptomycin in those who received this drug may have influenced outcome. The late follow-up showed a cumulative relapse rate of 13% over five years in those who had achieved negative cultures initially, and the relapse rate did not appear to be influenced by pulmonary resection as part of the treatment.

There is considerable small-scale agricultural production in Hungary, and these capacities are suited for such production which the large-scale farms do not undertake for either technical or economic reasons. But the economic weight of small-scale production depends on the closeness of their integration with large-scale farms and the enterprises. Numerous examples prove that their integration with large-scale farms, processing and preserving (canning) enterprises is advantageous for the national economy and useful for the small-scale producers themselves.

This paper retrospectively reviews various complaints and disciplinary cases that have appeared before chiropractic provincial regulatory boards throughout Canada, and have resulted in a significant outcome. This information was compiled by the Disciplinary Records Committee of the Canadian Federation of Chiropractic Regulatory Boards. Annually, the committee recorded the following; jurisdiction, year of disciplinary decision, nature of charge/allegation, specific mitigating factors, findings/outcome, penalties imposed, costs related to proceedings, who costs were attributed to, formal or informal proceeding(s). A total of 99 complaints are reviewed. In addition to demographic analysis of the data, a series of descriptive cases are included. This information is provided for the purpose of examining any parallels that might exist when chiropractic regulatory boards evaluate cases so they might arrive at conclusions in a fair and reasonable manner. Consistency in the application of rules and sanctions is a desirable objective of all chiropractic regulatory boards. While this paper is disseminated for informative purposes, ultimately each provincial regulatory board must exhibit good judgement with respect to case-specific issues.

I learned all this three years ago when I had to do extensive research on sunscreen and skin cancer for a newspaper article. I was shocked to learn how easily your skin can be permanently damaged by UV rays. (Though, I have to admit I was way more shocked to find out that some coral reef fish produce and secrete their own SPF 15 sunscreen. No kidding.)

Though I've been out of the dating scene for four years now, I always think fondly of those single years. I'd hit the bars with my girlfriends after work, go shopping at Wal-Mart at 2 a.m. and eat Froot Loops for dinner without any hesitation. It was great.

This really shouldn't surprise anyone. For decades women have been fighting for equality in the workplace. Our numbers have grown in many historically male-dominated fields including law and engineering. And it's no longer an anomaly for some women to be the breadwinners in their families. More women are attending college than ever before, often surpassing the number of male students on campus.

So wouldn't it make sense? [Harry Potter] throwing his scrawny 17-year- old body in front of Lord Voldemort's poised wand to save his best friends, Ron Weasley and Hermoine Granger? It would be the kind of heroic move we've come to expect from Harry.