Terminology Shift Announced by Britain's National Cyber Security Center
Forget "whitelists" and "blacklists" in cybersecurity. So recommends Britain's National Cyber Security Center, in a bid to move beyond the racial connotations inherent to the terminology. Henceforth, NCSC - part of intelligence agency GCHQ - will use the terms "allow list" and "deny list." Will others follow?

Terminology Shift Announced by Britain's National Cyber Security Center
Forget "whitelists" and "blacklists" in cybersecurity. So recommends Britain's National Cyber Security Center, in a bid to move beyond the racial connotations inherent to the terminology. Henceforth, NCSC - part of intelligence agency GCHQ - will use the terms "allow list" and "deny list." Will others follow?

Terminology Shift Announced by Britain's National Cyber Security Center
Forget "whitelists" and "blacklists" in cybersecurity. So recommends Britain's National Cyber Security Center, in a bid to move beyond the racial connotations inherent to the terminology. Henceforth, NCSC - part of intelligence agency GCHQ - will use the terms "allow list" and "deny list." Will others follow?

Terminology Shift Announced by Britain's National Cyber Security Center
Forget "whitelists" and "blacklists" in cybersecurity. So recommends Britain's National Cyber Security Center, in a bid to move beyond the racial connotations inherent to the terminology. Henceforth, NCSC - part of intelligence agency GCHQ - will use the terms "allow list" and "deny list." Will others follow?

Terminology Shift Announced by Britain's National Cyber Security Center
Forget "whitelists" and "blacklists" in cybersecurity. So recommends Britain's National Cyber Security Center, in a bid to move beyond the racial connotations inherent to the terminology. Henceforth, NCSC - part of intelligence agency GCHQ - will use the terms "allow list" and "deny list." Will others follow?

Terminology Shift Announced by Britain's National Cyber Security Center
Forget "whitelists" and "blacklists" in cybersecurity. So recommends Britain's National Cyber Security Center, in a bid to move beyond the racial connotations inherent to the terminology. Henceforth, NCSC - part of intelligence agency GCHQ - will use the terms "allow list" and "deny list." Will others follow?

Terminology Shift Announced by Britain's National Cyber Security Center
Forget "whitelists" and "blacklists" in cybersecurity. So recommends Britain's National Cyber Security Center, in a bid to move beyond the racial connotations inherent to the terminology. Henceforth, NCSC - part of intelligence agency GCHQ - will use the terms "allow list" and "deny list." Will others follow?

Terminology Shift Announced by Britain's National Cyber Security Center
Forget "whitelists" and "blacklists" in cybersecurity. So recommends Britain's National Cyber Security Center, in a bid to move beyond the racial connotations inherent to the terminology. Henceforth, NCSC - part of intelligence agency GCHQ - will use the terms "allow list" and "deny list." Will others follow?

Terminology Shift Announced by Britain's National Cyber Security Center
Forget "whitelists" and "blacklists" in cybersecurity. So recommends Britain's National Cyber Security Center, in a bid to move beyond the racial connotations inherent to the terminology. Henceforth, NCSC - part of intelligence agency GCHQ - will use the terms "allow list" and "deny list." Will others follow?

Terminology Shift Announced by Britain's National Cyber Security Center
Forget "whitelists" and "blacklists" in cybersecurity. So recommends Britain's National Cyber Security Center, in a bid to move beyond the racial connotations inherent to the terminology. Henceforth, NCSC - part of intelligence agency GCHQ - will use the terms "allow list" and "deny list." Will others follow?

Terminology Shift Announced by Britain's National Cyber Security Center
Forget "whitelists" and "blacklists" in cybersecurity. So recommends Britain's National Cyber Security Center, in a bid to move beyond the racial connotations inherent to the terminology. Henceforth, NCSC - part of intelligence agency GCHQ - will use the terms "allow list" and "deny list." Will others follow?

Terminology Shift Announced by Britain's National Cyber Security Center
Forget "whitelists" and "blacklists" in cybersecurity. So recommends Britain's National Cyber Security Center, in a bid to move beyond the racial connotations inherent to the terminology. Henceforth, NCSC - part of intelligence agency GCHQ - will use the terms "allow list" and "deny list." Will others follow?

Terminology Shift Announced by Britain's National Cyber Security Center
Forget "whitelists" and "blacklists" in cybersecurity. So recommends Britain's National Cyber Security Center, in a bid to move beyond the racial connotations inherent to the terminology. Henceforth, NCSC - part of intelligence agency GCHQ - will use the terms "allow list" and "deny list." Will others follow?

Terminology Shift Announced by Britain's National Cyber Security Center
Forget "whitelists" and "blacklists" in cybersecurity. So recommends Britain's National Cyber Security Center, in a bid to move beyond the racial connotations inherent to the terminology. Henceforth, NCSC - part of intelligence agency GCHQ - will use the terms "allow list" and "deny list." Will others follow?

Terminology Shift Announced by Britain's National Cyber Security Center
Forget "whitelists" and "blacklists" in cybersecurity. So recommends Britain's National Cyber Security Center, in a bid to move beyond the racial connotations inherent to the terminology. Henceforth, NCSC - part of intelligence agency GCHQ - will use the terms "allow list" and "deny list." Will others follow?

Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

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ISLAMABAD: A senior member of the Prime Minister’s Office has approached the Federal Ombudsman over the ‘extreme injustice’ of out of turn allotment of second residential plots in the federal capital to a selected few in the bureaucracy in a non-transparent and unjust manner.The...

ISLAMABAD: A senior member of the Prime Minister’s Office has approached the Federal Ombudsman over the ‘extreme injustice’ of out of turn allotment of second residential plots in the federal capital to a selected few in the bureaucracy in a non-transparent and unjust manner. The...

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KOCHI: You have got some disposable amount, and want to own a real estate asset abroad. Now, it is possible as the Reserve Bank of India (RBI) allows resident Indians to remit money abroad for the purchase of immovable properties. According to a new RBI directive, banks are allowed to remit up to US$125,000 (around Rs 75 lakh) every financial year for any permitted current or capital account transaction, or a combination of both. The money can be used for purchasing immovable property outside India. Financial experts point out that the new norms might be helpful for the state as it would be easier for Keralites to spot properties due […]

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Title: Allow Dead Men to Be Sperm Donors, Medical Ethicists Say
Category: Health News
Created: 1/22/2020 12:00:00 AM
Last Editorial Review: 1/22/2020 12:00:00 AM

ABSTRACT

Production of metallo-β-lactamases (MBLs), which hydrolyze carbapenems, is a cause of carbapenem resistance in Enterobacteriaceae. Development of effective inhibitors for MBLs is one approach to restore carbapenem efficacy in carbapenem-resistant Enterobacteriaceae (CRE). We report here that sulfamoyl heteroarylcarboxylic acids (SHCs) can competitively inhibit the globally spreading and clinically relevant MBLs (i.e., IMP-, NDM-, and VIM-type MBLs) at nanomolar to micromolar orders of magnitude. Addition of SHCs restored meropenem efficacy against 17/19 IMP-type and 7/14 NDM-type MBL-producing Enterobacteriaceae to satisfactory clinical levels. SHCs were also effective against IMP-type MBL-producing Acinetobacter spp. and engineered Escherichia coli strains overproducing individual minor MBLs (i.e., TMB-2, SPM-1, DIM-1, SIM-1, and KHM-1). However, SHCs were less effective against MBL-producing Pseudomonas aeruginosa. Combination therapy with meropenem and SHCs successfully cured mice infected with IMP-1-producing E. coli and dually NDM-1/VIM-1-producing Klebsiella pneumoniae clinical isolates. X-ray crystallographic analyses revealed the inhibition mode of SHCs against MBLs; the sulfamoyl group of SHCs coordinated to two zinc ions, and the carboxylate group coordinated to one zinc ion and bound to positively charged amino acids Lys224/Arg228 conserved in MBLs. Preclinical testing revealed that the SHCs showed low toxicity in cell lines and mice and high stability in human liver microsomes. Our results indicate that SHCs are promising lead compounds for inhibitors of MBLs to combat MBL-producing CRE.

IMPORTANCE Carbapenem antibiotics are the last resort for control of severe infectious diseases, bloodstream infections, and pneumonia caused by Gram-negative bacteria, including Enterobacteriaceae. However, carbapenem-resistant Enterobacteriaceae (CRE) strains have spread globally and are a critical concern in clinical settings because CRE infections are recognized as a leading cause of increased mortality among hospitalized patients. Most CRE produce certain kinds of serine carbapenemases (e.g., KPC- and GES-type β-lactamases) or metallo-β-lactamases (MBLs), which can hydrolyze carbapenems. Although effective MBL inhibitors are expected to restore carbapenem efficacy against MBL-producing CRE, no MBL inhibitor is currently clinically available. Here, we synthesized 2,5-diethyl-1-methyl-4-sulfamoylpyrrole-3-carboxylic acid (SPC), which is a potent inhibitor of MBLs. SPC is a remarkable lead compound for clinically useful MBL inhibitors and can potentially provide a considerable benefit to patients receiving treatment for lethal infectious diseases caused by MBL-producing CRE.

Key Points

IMMUNOLOGY AND INFLAMMATION Correction for “Treg-mediated prolonged survival of skin allografts without immunosuppression,” by Nina Pilat, Mario Wiletel, Anna M. Weijler, Romy Steiner, Benedikt Mahr, Joanna Warren, Theresa M. Corpuz, Thomas Wekerle, Kylie E. Webster, and Jonathan Sprent, which was first published June 13, 2019; 10.1073/pnas.1903165116 (Proc. Natl. Acad. Sci....

Formate oxidation to carbon dioxide is a key reaction in one-carbon compound metabolism, and its reverse reaction represents the first step in carbon assimilation in the acetogenic and methanogenic branches of many anaerobic organisms. The molybdenum-containing dehydrogenase FdsABG is a soluble NAD+-dependent formate dehydrogenase and a member of the NADH dehydrogenase superfamily. Here, we present the first structure of the FdsBG subcomplex of the cytosolic FdsABG formate dehydrogenase from the hydrogen-oxidizing bacterium Cupriavidus necator H16 both with and without bound NADH. The structures revealed that the two iron-sulfur clusters, Fe4S4 in FdsB and Fe2S2 in FdsG, are closer to the FMN than they are in other NADH dehydrogenases. Rapid kinetic studies and EPR measurements of rapid freeze-quenched samples of the NADH reduction of FdsBG identified a neutral flavin semiquinone, FMNH•, not previously observed to participate in NADH-mediated reduction of the FdsABG holoenzyme. We found that this semiquinone forms through the transfer of one electron from the fully reduced FMNH−, initially formed via NADH-mediated reduction, to the Fe2S2 cluster. This Fe2S2 cluster is not part of the on-path chain of iron-sulfur clusters connecting the FMN of FdsB with the active-site molybdenum center of FdsA. According to the NADH-bound structure, the nicotinamide ring stacks onto the re-face of the FMN. However, NADH binding significantly reduced the electron density for the isoalloxazine ring of FMN and induced a conformational change in residues of the FMN-binding pocket that display peptide-bond flipping upon NAD+ binding in proper NADH dehydrogenases.

Allostery exploits the conformational dynamics of enzymes by triggering a shift in population ensembles toward functionally distinct conformational or dynamic states. Allostery extensively regulates the activities of key enzymes within biosynthetic pathways to meet metabolic demand for their end products. Here, we have examined a critical enzyme, 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS), at the gateway to aromatic amino acid biosynthesis in Mycobacterium tuberculosis, which shows extremely complex dynamic allostery: three distinct aromatic amino acids jointly communicate occupancy to the active site via subtle changes in dynamics, enabling exquisite fine-tuning of delivery of these essential metabolites. Furthermore, this allosteric mechanism is co-opted by pathway branchpoint enzyme chorismate mutase upon complex formation. In this study, using statistical coupling analysis, site-directed mutagenesis, isothermal calorimetry, small-angle X-ray scattering, and X-ray crystallography analyses, we have pinpointed a critical node within the complex dynamic communication network responsible for this sophisticated allosteric machinery. Through a facile Gly to Pro substitution, we have altered backbone dynamics, completely severing the allosteric signal yet remarkably, generating a nonallosteric enzyme that retains full catalytic activity. We also identified a second residue of prime importance to the inter-enzyme communication with chorismate mutase. Our results reveal that highly complex dynamic allostery is surprisingly vulnerable and provide further insights into the intimate link between catalysis and allostery.

Differences in REE patterns of calcite from extensional and shear veins of the Sestola Vidiciatico Tectonic Unit in the Northern Apennines suggest variations in fluid source during the seismic cycle in an ancient analogue of a shallow megathrust (T_max c. 100–150°C). In shear veins, a positive Eu anomaly suggests an exotic fluid source, probably hotter than the fault environment. Small-scale extensional veins were derived instead from a local fluid in equilibrium with the fault rocks. Mutually crosscutting relations between two extensional vein sets, parallel and perpendicular to the megathrust, suggest repeated shifting of the ₁ and ₃ stresses during the seismic cycle. This is consistent with: (1) a seismic phase, with brittle failure along the thrust, crystallization of shear veins from an exotic fluid, stress drop and stress rotation; (2) a post-seismic phase, with fault-normal compaction and formation of fault-normal extensional veins fed by local fluids; (3) a reloading phase, where shear stress and pore pressure are gradually restored and fault-parallel extensional veins form, until the thrust fails again. The combination of geochemical and structural analyses in veins from exhumed megathrust analogues represents a promising tool to better understand the interplay between stress state and fluids in modern subduction zones.

Supplementary material: Cathodoluminescence microphotographs, methodological details of the microstructural analysis, microphotographs of the location of analysed spots and a geochemical data table are available at https://doi.org/10.6084/m9.figshare.c.4842165

Thematic collection: This article is part of the Polygenetic mélanges collection available at: https://www.lyellcollection.org/cc/polygenetic-melanges