Holcomb and Hogsett say they are on the same page.

Muhabirimiz Martin Buckley 1980'lerde adı Bombayken çalışıp yaşadığı Mumbai'ye uzun süre sonra bir kez daha gitti, kentin değişen ve değişmeyen yönlerini anlamaya çalıştı.

We hear about the book that is 85% classic literature, 15% zombie horror. How did Jane Austen get so mashed-up?

The governor said state officials are trying to manage health risks, job risks and budget risks simultaneously.

The governor offered a gentle rebuke to protesters: You're not helping.

Indiana Gov. Eric Holcomb's responsibility and obligation is to the citizenry of Indiana, a letter to the editor says.

Until we have a vaccine, the road to opening is through a health care system which can handle the infection, a letter to the editor says.

Indianapolis Mayor Joe Hogsett strained to embody unity Thursday at a time when it would have been easy to perceive friction.

Gov. Eric Holcomb's plan to reopen Indiana puts the burden on individuals instead of government.

A chronology of key events

Key facts, figures and dates

It's difficult to count the number of video games in which someone is standing around a corner clutching a weapon and waiting for their mortal enemy to pass. But until recently it wasn't possible to physically experience that scenario.

From Ronald Reagan's "evil empire" to Mark Hamill battling Ivanka Trump.

The true star of “Resident Evil 3” is its supurb graphics engine.

The host made news of his own with questionable jokes, an eye roll and whispers of another wrong winner.

Colombia

The Amateur Traveler talks to David Lee about his parttime home, the “City of the Eternal Spring”, Medellin Colombia. If you just Medellin as a dangerous city and the home of drug lords, then your information is about 20 years out of date

Hear about travel to Lombok in Indonesia as the Amateur Traveler talks to Jason Andrew Jenkins from AnEpicEducation.com about his family's recent 5 week trip to this island paradise.

Hear about travel to the coffee region of Colombia as the Amateur Traveler talks to Alejandro from Bogota about an area of his country that he thinks doesn't get enough attention.

Hear about travel to Lombok in Indonesia as the Amateur Traveler talks to Jason Andrew Jenkins from AnEpicEducation.com about his family's recent 5 week trip to this island paradise.

As ISIS expands its reach into Afghanistan, it is training children and teenagers to become the next generation of jihadis.

The LockPickingLawyer easily opens this Yale Y500 Combination Key Access padlock with just a sliver of aluminum from a soda can.

Read the rest

N. Leigh Anderson
Apr 1, 2004; 3:311-326
Research

Christian Tagwerker
Apr 1, 2006; 5:737-748
Research

In Staphylococcus aureus–caused endocarditis, the pathogen secretes staphylocoagulase (SC), thereby activating human prothrombin (ProT) and evading immune clearance. A previous structural comparison of the SC(1–325) fragment bound to thrombin and its inactive precursor prethrombin 2 has indicated that SC activates ProT by inserting its N-terminal dipeptide Ile1-Val2 into the ProT Ile16 pocket, forming a salt bridge with ProT's Asp194, thereby stabilizing the active conformation. We hypothesized that these N-terminal SC residues modulate ProT binding and activation. Here, we generated labeled SC(1–246) as a probe for competitively defining the affinities of N-terminal SC(1–246) variants preselected by modeling. Using ProT(R155Q,R271Q,R284Q) (ProTQQQ), a variant refractory to prothrombinase- or thrombin-mediated cleavage, we observed variant affinities between ∼1 and 650 nm and activation potencies ranging from 1.8-fold that of WT SC(1–246) to complete loss of function. Substrate binding to ProTQQQ caused allosteric tightening of the affinity of most SC(1–246) variants, consistent with zymogen activation through occupation of the specificity pocket. Conservative changes at positions 1 and 2 were well-tolerated, with Val1-Val2, Ile1-Ala2, and Leu1-Val2 variants exhibiting ProTQQQ affinity and activation potency comparable with WT SC(1–246). Weaker binding variants typically had reduced activation rates, although at near-saturating ProTQQQ levels, several variants exhibited limiting rates similar to or higher than that of WT SC(1–246). The Ile16 pocket in ProTQQQ appears to favor nonpolar, nonaromatic residues at SC positions 1 and 2. Our results suggest that SC variants other than WT Ile1-Val2-Thr3 might emerge with similar ProT-activating efficiency.

4 March 2020 , Volume 96, Number 2

4 March 2020 , Volume 96, Number 2

Mohamed Jleli, Bessem Samet and Philippe Souplet
Proc. Amer. Math. Soc. 148 (2020), 2579-2593.
Abstract, references and article information