ule Two new biosafety self-paced learning modules on public access to biosafety information and public participation in decision-making regarding LMOs are available in the new e-Learning Platform By scbd.unssc.org Published On :: Thu, 02 Mar 2017 00:00:00 GMT Full Article
ule CBD News: I am pleased to welcome you all to the eleventh meeting of the Liaison Group on Capacity-building for Biosafety here in Montreal. I wish to thank you all for taking time from your busy schedules to attend this meeting, which is expected to play By www.cbd.int Published On :: Mon, 14 Mar 2016 00:00:00 GMT Full Article
ule CBD News: The global community will lay the groundwork for action over the next few decades to protect biodiversity and nature at the 2018 UN Biodiversity Conference, scheduled to take place in Sharm El Sheikh, Egypt from 17 to 29 November 2018. By www.cbd.int Published On :: Thu, 08 Nov 2018 00:00:00 GMT Full Article
ule CBD News: Two meetings of the UN Convention on Biological Diversity's (CBD) permanent subsidiary bodies originally scheduled for May 2020 and then rescheduled for August/September 2020 will now take place in August 2020. By www.cbd.int Published On :: Thu, 02 Apr 2020 00:00:00 GMT Full Article
ule What startups need to know about new UK immigration rules By www.techworld.com Published On :: Wed, 26 Feb 2020 08:37:00 GMT The government has unveiled its new points-based immigration system, due to come into force in 2021, we break down what it means for the UK startup sector Full Article
ule Modified Euler scheme for the weak approximation of stochastic differential equations driven by the Wiener process By www.ams.org Published On :: Mon, 02 Mar 2020 06:58 EST S. V. Bodnarchuk and O. M. Kulyk Theor. Probability and Math. Statist. 99 (2020), 53-65. Abstract, references and article information Full Article
ule A topology on the set of isomorphism classes of maximal Cohen–Macaulay modules By www.ams.org Published On :: Thu, 02 Apr 2020 13:59 EDT Naoya Hiramatsu and Ryo Takahashi Proc. Amer. Math. Soc. 148 (2020), 2359-2369. Abstract, references and article information Full Article
ule Lawbreaking violates rule of law By www.news.gov.hk Published On :: Sun, 22 Dec 2019 00:00:00 +0800 The violence and vandalism in recent months sparked a crisis of confidence of our rule of law. The so-called justice lawbreaking or civil disobedience is never justified under the law. I urge all of you not to engage in any illegal activities. The Court of Final Appeal in its judgment (FACC8-10/2017) pointed out that: (1) unlawful assemblies involving violence, even a relatively low degree, will not be condoned and may justifiably attract sentences of immediate imprisonment in the future; and (2) little weight will be given to the mitigation that the offending act was committed in the exercise of constitutional rights or acts of civil disobedience because the fact of a conviction will necessarily mean the offender has crossed the line separating the lawful exercise of his constitutional rights from unlawful activity subject to sanctions and constraints. There are suggestions that deliberate lawbreaking might be considered to achieve objectives, however, this would bring a wrong concept of the rule of law. The escalated violence and vandalism in the last few months have also undermined the perception of the rule of law among the public. My colleagues and I would promote and publicise the correct concept of the rule of law to the citizens through different channels. In analysing the current situation, I hope that we all could remain reasonable and objective by keeping an open mind, being informed and considering all relevant facts before coming to a conclusion. Our rule of law has been highly regarded, and such an achievement was not easy to come by. We should all join hands to cherish and safeguard our rule of law. Abiding by the law is one of the many obligations that ought to be observed by the public. Law exists in practice but it should not only be practised by lawyers, judges and governments. More importantly, the rule of law should be observed and respected by the community as a whole. The Government would continue to be strongly committed to upholding the rule of law. Secretary for Justice Teresa Cheng wrote this article and posted it on her blog on December 22. Full Article
ule Alleged rule breaches probed By www.news.gov.hk Published On :: Tue, 05 May 2020 00:00:00 +0800 (To watch the full press briefing with sign language interpretation, click here.) Chief Executive Carrie Lam today said law enforcement agencies are investigating cases where police officers are suspected of breaching property rules and will give a full account to society. Speaking to reporters before the Executive Council meeting this morning, Mrs Lam said nobody is above the law. “The law will be applied in the same manner regardless of the status, the background, the political affiliation of that particular person. “As far as I am concerned, as the Chief Executive of Hong Kong and also as an individual, no law-breaking behaviour is acceptable. But it is not for me to stand here to judge each and every case because every case or every complaint has to be investigated and analysed by the law enforcement agencies. “I am sure that they will do it as diligently as possible and will give a full account to society, especially given the recent concerns.” Full Article
ule DeepMind founder Mustafa Suleyman leaves indefinitely By www.techworld.com Published On :: Thu, 22 Aug 2019 08:35:00 GMT DeepMind's cofounder and head of applied artificial intelligence, Mustafa Suleyman, has abruptly left the company for an indefinite period Full Article
ule Water-splitting module a source of perpetual energy By www.eurekalert.org Published On :: Mon, 04 May 2020 00:00:00 EDT (Rice University) Rice University researchers have integrated high-efficiency solar cells and electrode catalysts into an efficient, low-cost device that splits water to produce hydrogen fuel. Full Article
ule Scheduled premises' rules clarified By www.news.gov.hk Published On :: Fri, 08 May 2020 00:00:00 +0800 Premises can still operate other licensed businesses which are not required to be suspended if they were operating more than one licensed business before the closure, the Food & Health Bureau said today. The bureau made the statement in response to media enquiries on some anti-epidemic measures which were relaxed from today. The statement noted that in accordance with the Prevention & Control of Disease (Requirements & Directions) (Business & Premises) Regulation, the Secretary for Food & Health has issued directions by notices in the Gazette that certain scheduled premises, namely karaoke establishments, clubs or nightclubs, party rooms and bathhouses, should remain closed until May 21. These scheduled premises may still operate other licensed businesses if the operators have implemented all measures to effectively stop or avoid operation of businesses and offering services which are required to be suspended. For example, premises originally operated as karaoke establishments and catering businesses can continue their catering business in accordance with the relevant directions if all karaoke operation and services are suspended. The directions state that facilities, installations and equipment for karaoke activities are closed or properly sealed off and notices are posted in prominent locations at the entrances clearly indicating that only catering services but no karaoke services are provided in the premises. Other scheduled premises operating more than one licensed business can adopt similar measures to operate other licensed businesses which are not required to be suspended, the bureau added. Full Article
ule Structures of the MHC-I molecule BF2*1501 disclose the preferred presentation of an H5N1 virus-derived epitope [Protein Structure and Folding] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 Lethal infections by strains of the highly-pathogenic avian influenza virus (HPAIV) H5N1 pose serious threats to both the poultry industry and public health worldwide. A lack of confirmed HPAIV epitopes recognized by cytotoxic T lymphocytes (CTLs) has hindered the utilization of CD8+ T-cell–mediated immunity and has precluded the development of effectively diversified epitope-based vaccination approaches. In particular, an HPAIV H5N1 CTL-recognized epitope based on the peptide MHC-I–β2m (pMHC-I) complex has not yet been designed. Here, screening a collection of selected peptides of several HPAIV strains against a specific pathogen-free pMHC-I (pBF2*1501), we identified a highly-conserved HPAIV H5N1 CTL epitope, named HPAIV–PA123–130. We determined the structure of the BF2*1501–PA123–130 complex at 2.1 Å resolution to elucidate the molecular mechanisms of a preferential presentation of the highly-conserved PA123–130 epitope in the chicken B15 lineage. Conformational characteristics of the PA123–130 epitope with a protruding Tyr-7 residue indicated that this epitope has great potential to be recognized by specific TCRs. Moreover, significantly increased numbers of CD8+ T cells specific for the HPAIV–PA123–130 epitope in peptide-immunized chickens indicated that a repertoire of CD8+ T cells can specifically respond to this epitope. We anticipate that the identification and structural characterization of the PA123–130 epitope reported here could enable further studies of CTL immunity against HPAIV H5N1. Such studies may aid in the development of vaccine development strategies using well-conserved internal viral antigens in chickens. Full Article
ule N{alpha}-Acetylation of the virulence factor EsxA is required for mycobacterial cytosolic translocation and virulence [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-04-24T06:08:45-07:00 The Mycobacterium tuberculosis virulence factor EsxA and its chaperone EsxB are secreted as a heterodimer (EsxA:B) and are crucial for mycobacterial escape from phagosomes and cytosolic translocation. Current findings support the idea that for EsxA to interact with host membranes, EsxA must dissociate from EsxB at low pH. However, the molecular mechanism by which the EsxA:B heterodimer separates is not clear. In the present study, using liposome-leakage and cytotoxicity assays, LC-MS/MS–based proteomics, and CCF-4 FRET analysis, we obtained evidence that the Nα-acetylation of the Thr-2 residue on EsxA, a post-translational modification that is present in mycobacteria but absent in Escherichia coli, is required for the EsxA:B separation. Substitutions at Thr-2 that precluded Nα-acetylation inhibited the heterodimer separation and hence prevented EsxA from interacting with the host membrane, resulting in attenuated mycobacterial cytosolic translocation and virulence. Molecular dynamics simulations revealed that at low pH, the Nα-acetylated Thr-2 makes direct and frequent “bind-and-release” contacts with EsxB, which generates a force that pulls EsxB away from EsxA. In summary, our findings provide evidence that the Nα-acetylation at Thr-2 of EsxA facilitates dissociation of the EsxA:B heterodimer required for EsxA membrane permeabilization and mycobacterial cytosolic translocation and virulence. Full Article
ule Single-molecule level structural dynamics of DNA unwinding by human mitochondrial Twinkle helicase [Molecular Biophysics] By www.jbc.org Published On :: 2020-04-24T06:08:45-07:00 Knowledge of the molecular events in mitochondrial DNA (mtDNA) replication is crucial to understanding the origins of human disorders arising from mitochondrial dysfunction. Twinkle helicase is an essential component of mtDNA replication. Here, we employed atomic force microscopy imaging in air and liquids to visualize ring assembly, DNA binding, and unwinding activity of individual Twinkle hexamers at the single-molecule level. We observed that the Twinkle subunits self-assemble into hexamers and higher-order complexes that can switch between open and closed-ring configurations in the absence of DNA. Our analyses helped visualize Twinkle loading onto and unloading from DNA in an open-ringed configuration. They also revealed that closed-ring conformers bind and unwind several hundred base pairs of duplex DNA at an average rate of ∼240 bp/min. We found that the addition of mitochondrial single-stranded (ss) DNA–binding protein both influences the ways Twinkle loads onto defined DNA substrates and stabilizes the unwound ssDNA product, resulting in a ∼5-fold stimulation of the apparent DNA-unwinding rate. Mitochondrial ssDNA-binding protein also increased the estimated translocation processivity from 1750 to >9000 bp before helicase disassociation, suggesting that more than half of the mitochondrial genome could be unwound by Twinkle during a single DNA-binding event. The strategies used in this work provide a new platform to examine Twinkle disease variants and the core mtDNA replication machinery. They also offer an enhanced framework to investigate molecular mechanisms underlying deletion and depletion of the mitochondrial genome as observed in mitochondrial diseases. Full Article
ule Delineating an extracellular redox-sensitive module in T-type Ca2+ channels [Membrane Biology] By www.jbc.org Published On :: 2020-05-01T00:06:09-07:00 T-type (Cav3) Ca2+ channels are important regulators of excitability and rhythmic activity of excitable cells. Among other voltage-gated Ca2+ channels, Cav3 channels are uniquely sensitive to oxidation and zinc. Using recombinant protein expression in HEK293 cells, patch clamp electrophysiology, site-directed mutagenesis, and homology modeling, we report here that modulation of Cav3.2 by redox agents and zinc is mediated by a unique extracellular module containing a high-affinity metal-binding site formed by the extracellular IS1–IS2 and IS3–IS4 loops of domain I and a cluster of extracellular cysteines in the IS1–IS2 loop. Patch clamp recording of recombinant Cav3.2 currents revealed that two cysteine-modifying agents, sodium (2-sulfonatoethyl) methanethiosulfonate (MTSES) and N-ethylmaleimide, as well as a reactive oxygen species–producing neuropeptide, substance P (SP), inhibit Cav3.2 current to similar degrees and that this inhibition is reversed by a reducing agent and a zinc chelator. Pre-application of MTSES prevented further SP-mediated current inhibition. Substitution of the zinc-binding residue His191 in Cav3.2 reduced the channel's sensitivity to MTSES, and introduction of the corresponding histidine into Cav3.1 sensitized it to MTSES. Removal of extracellular cysteines from the IS1–IS2 loop of Cav3.2 reduced its sensitivity to MTSES and SP. We hypothesize that oxidative modification of IS1–IS2 loop cysteines induces allosteric changes in the zinc-binding site of Cav3.2 so that it becomes sensitive to ambient zinc. Full Article
ule Structure-based discovery of a small-molecule inhibitor of methicillin-resistant Staphylococcus aureus virulence [Molecular Biophysics] By www.jbc.org Published On :: 2020-05-01T00:06:09-07:00 The rapid emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) strains poses a major threat to public health. MRSA possesses an arsenal of secreted host-damaging virulence factors that mediate pathogenicity and blunt immune defenses. Panton–Valentine leukocidin (PVL) and α-toxin are exotoxins that create lytic pores in the host cell membrane. They are recognized as being important for the development of invasive MRSA infections and are thus potential targets for antivirulence therapies. Here, we report the high-resolution X-ray crystal structures of both PVL and α-toxin in their soluble, monomeric, and oligomeric membrane-inserted pore states in complex with n-tetradecylphosphocholine (C14PC). The structures revealed two evolutionarily conserved phosphatidylcholine-binding mechanisms and their roles in modulating host cell attachment, oligomer assembly, and membrane perforation. Moreover, we demonstrate that the soluble C14PC compound protects primary human immune cells in vitro against cytolysis by PVL and α-toxin and hence may serve as the basis for the development of an antivirulence agent for managing MRSA infections. Full Article
ule New rules for the physical basis of cellular organelle composition By www.eurekalert.org Published On :: Wed, 06 May 2020 00:00:00 EDT (Princeton University, Engineering School) New findings about critical cellular structures have upended common assumptions about their formation and composition and provided new insight how molecular machines are built in living cells. Full Article
ule HIGD2A is required for assembly of the COX3 module of human mitochondrial complex IV By feedproxy.google.com Published On :: 2020-04-21 Daniella H HockApr 21, 2020; 0:RA120.002076v1-mcp.RA120.002076Research Full Article
ule High Resolution Depth-Encoding PET Detector Module with Prismatoid Light Guide Array By jnm.snmjournals.org Published On :: 2020-02-28T13:52:17-08:00 Depth-encoding detectors with single-ended readout provide a practical, cost-effective approach for constructing high resolution and high sensitivity PET scanners. However, the current iteration of such detectors utilizes a uniform glass light guide to achieve depth-encoding, resulting in non-uniform performance throughout the detector array due to suboptimal intercrystal light sharing. We introduce Prism-PET, a single-ended readout PET detector module with a segmented light guide composed of an array of prismatoids that introduces enhanced, deterministic light sharing. Methods: High resolution PET detector modules were fabricated with single-ended readout of polished multicrystal lutetium yttrium orthosilicate (LYSO) scintillator arrays directly coupled 4-to-1 and 9-to-1 to arrays of 3.2 x 3.2 mm2 silicon photomultiplier pixels. Each scintillator array was coupled at the non-readout side to a light guide (one 4-to-1 module with a uniform glass light guide, one 4-to-1 Prism-PET module and one 9-to-1 Prism-PET module) to introduce intercrystal light sharing, which closely mimics the behavior of dual-ended readout with the additional benefit of improved crystal identification. Flood histogram data was acquired using a 3 MBq Na-22 source to characterize crystal identification and energy resolution. Lead collimation was used to acquire data at specific depths to determine depth-of-interaction (DOI) resolution. Results: The flood histogram measurements showed excellent and uniform crystal separation throughout the Prism-PET modules while the uniform glass light guide module had performance degradation at the edges and corners. A DOI resolution of 5.0 mm full width at half maximum (FWHM) and energy resolution of 13% were obtained in the uniform glass light guide module. By comparison, the 4-to-1 coupled Prism-PET module achieved 2.5 mm FWHM DOI resolution and 9% energy resolution. Conclusion: PET scanners based on our Prism-PET modules with segmented prismatoid light guide arrays can achieve high and uniform spatial resolution (9-to-1 coupling with ~ 1 mm crystals), high sensitivity, good energy and timing resolutions (using polished crystals and after applying DOI-correction), and compact size (depth-encoding eliminates parallax error and permits smaller ring-diameter). Full Article
ule Blistering1 Modulates Penicillium expansum Virulence Via Vesicle-mediated Protein Secretion [Research] By feedproxy.google.com Published On :: 2020-02-01T00:05:30-08:00 The blue mold fungus, Penicillium expansum, is a postharvest apple pathogen that contributes to food waste by rotting fruit and by producing harmful mycotoxins (e.g. patulin). To identify genes controlling pathogen virulence, a random T-DNA insertional library was created from wild-type P. expansum strain R19. One transformant, T625, had reduced virulence in apples, blistered mycelial hyphae, and a T-DNA insertion that abolished transcription of the single copy locus in which it was inserted. The gene, Blistering1, encodes a protein with a DnaJ domain, but otherwise has little homology outside the Aspergillaceae, a family of fungi known for producing antibiotics, mycotoxins, and cheese. Because protein secretion is critical for these processes and for host infection, mass spectrometry was used to monitor proteins secreted into liquid media during fungal growth. T625 failed to secrete a set of enzymes that degrade plant cell walls, along with ones that synthesize the three final biosynthetic steps of patulin. Consequently, the culture broth of T625 had significantly reduced capacity to degrade apple tissue and contained 30 times less patulin. Quantitative mass spectrometry of 3,282 mycelial proteins revealed that T625 had altered cellular networks controlling protein processing in the endoplasmic reticulum, protein export, vesicle-mediated transport, and endocytosis. T625 also had reduced proteins controlling mRNA surveillance and RNA processing. Transmission electron microscopy of hyphal cross sections confirmed that T625 formed abnormally enlarged endosomes or vacuoles. These data reveal that Blistering1 affects internal and external protein processing involving vesicle-mediated transport in a family of fungi with medical, commercial, and agricultural importance. Full Article
ule Digital Transformation Office chief executive Paul Shetler announces public service work schedule By www.smh.com.au Published On :: Wed, 14 Oct 2015 05:50:39 GMT Paul Shetler reveals the digital projects about to hit the federal bureaucracy. Starting with Canberra. Full Article
ule Characterization of the small molecule ARC39, a direct and specific inhibitor of acid sphingomyelinase in vitro By feedproxy.google.com Published On :: 2020-03-10 Eyad NaserMar 10, 2020; 0:jlr.RA120000682v1-jlr.RA120000682Research Articles Full Article
ule Episode 24 – The Internet of David’s Rules (IoDR) ARM, graphics cards & Twitter’s crackdown By play.acast.com Published On :: Fri, 22 Jul 2016 12:38:13 GMT Macworld UK’s Acting Editor David Price takes the reins for this edition, and is joined by Online Editor of Computerworld UK Scott Carey to chat about billions and billions of pounds and the acquisition of ARM by SoftBank. Second up, Staff Writer at PC Advisor and Macworld UK Christopher Minasians plugs in to the haunting world of graphics cards and makes sense of it all for the rest of us. Digital Arts Staff Writer Mimi Launder then explains why Twitter has slapped a troll right in the face in order to stand up to Internet bullying. See acast.com/privacy for privacy and opt-out information. Full Article
ule Characterization of the small molecule ARC39, a direct and specific inhibitor of acid sphingomyelinase in vitro [Research Articles] By feedproxy.google.com Published On :: 2020-03-10T13:30:31-07:00 Inhibition of acid sphingomyelinase (ASM), a lysosomal enzyme that catalyzes the hydrolysis of sphingomyelin into ceramide and phosphorylcholine, may serve as an investigational tool or a therapeutic intervention to control many diseases. Specific ASM inhibitors are currently not sufficiently characterized. Here, we found that 1-aminodecylidene bis-phosphonic acid (ARC39) specifically and efficiently (>90%) inhibits both lysosomal and secretory ASM in vitro. Results from investigating sphingomyelin phosphodiesterase 1 (SMPD1/Smpd1) mRNA and ASM protein levels suggested that ARC39 directly inhibits ASM’s catalytic activity in cultured cells, a mechanism which differs from that of functional inhibitors of ASM (FIASMAs). We further provide evidence that ARC39 dose- and time-dependently inhibits lysosomal ASM in intact cells, and we show that ARC39 also reduces platelet- and ASMpromoted adhesion of tumor cells. The observed toxicity of ARC39 is low at concentrations relevant for ASM inhibition in vitro, and it does not strongly alter the lysosomal compartment or induce phospholipidosis in vitro. When applied intraperitoneally in vivo, even subtoxic high doses administered short-term induced sphingomyelin accumulation only locally in the peritoneal lavage without significant accumulation in plasma, liver, spleen or brain. These findings require further investigation with other possible chemical modifications. In conclusion, our results indicate that ARC39 potently and selectively inhibits ASM in vitro and highlight the need for developing compounds that can reach tissue concentrations sufficient for ASM inhibition in vivo. Full Article
ule HIGD2A is required for assembly of the COX3 module of human mitochondrial complex IV [Research] By feedproxy.google.com Published On :: 2020-04-21T08:36:14-07:00 Assembly factors play a critical role in the biogenesis of mitochondrial respiratory chain complexes I-IV where they assist in the membrane insertion of subunits, attachment of co-factors, and stabilization of assembly intermediates. The major fraction of complexes I, III and IV are present together in large molecular structures known as respiratory chain supercomplexes. A number of assembly factors have been proposed as required for supercomplex assembly, including the hypoxia inducible gene 1 domain family member HIGD2A. Using gene-edited human cell lines and extensive steady state, translation and affinity enrichment proteomics techniques we show that loss of HIGD2A leads to defects in the de novo biogenesis of mtDNA-encoded COX3, subsequent accumulation of complex IV intermediates and turnover of COX3 partner proteins. Deletion of HIGD2A also leads to defective complex IV activity. The impact of HIGD2A loss on complex IV was not altered by growth under hypoxic conditions, consistent with its role being in basal complex IV assembly. While in the absence of HIGD2A we show that mitochondria do contain an altered supercomplex assembly, we demonstrate it to harbor a crippled complex IV lacking COX3. Our results redefine HIGD2A as a classical assembly factor required for building the COX3 module of complex IV. Full Article
ule Moscow's Domestic Policy: Russian Roulette By feedproxy.google.com Published On :: Wed, 15 Apr 2020 11:20:12 +0000 1 October 2008 , Number 4 Russia’s military action in Georgia was driven by Moscow’s domestic agenda. Foreign policy has become a tool of collective control back home. While the ‘ruling tandem’ has gained popularity, the new consensus does not provide for modernisation. Will the predatory state reform or collapse? Lilia Shevtsova Senior Associate, Carnegie Moscow Centre bear copy.jpg Full Article
ule Problem Notes for SAS®9 - 65295: The order of columns is not maintained when you select columns for output in the Business Rules transformation By feedproxy.google.com Published On :: Wed, 6 May 2020 10:01:07 EST In SAS Data Integration Studio, the columns that you select to include in the target table in a Business Rules transformation appear in the Selected columns area in a random order. Th Full Article DATABUILDER+SAS+Data+Integration+Studio
ule Problem Notes for SAS®9 - 65856: The process of updating a lookup table in SAS Business Rules Manager (running in UNIX operating environments) does not work properly By feedproxy.google.com Published On :: Mon, 27 Apr 2020 13:37:52 EST Under UNIX, the process of updating a lookup table in SAS Business Rules Manager does not work properly. The problem occurs when you perform these steps: Open a lookup table. Cl Full Article BRLSTBNDL+SAS+Business+Rules+Manager
ule Problem Notes for SAS®9 - 65869: SAS Visual Data Builder does not enable you to schedule with multiple time-event triggers By feedproxy.google.com Published On :: Fri, 24 Apr 2020 12:23:04 EST SAS Visual Data Builder might not enable you to create multiple time-event triggers. The + button to add another trigger is not available to select, as shown in the following display: imgalt="" src="{fusion_658 Full Article VISANLYTBNDL+SAS+Visual+Analytics
ule Inbox: How will potential new rule affect Rays? By mlb.mlb.com Published On :: Thu, 7 Feb 2019 11:50:31 EDT Rays beat reporter Juan Toribio answers fans' questions. Full Article
ule Thyroid nodules: diagnostic evaluation based on thyroid cancer risk assessment By feeds.bmj.com Published On :: Tuesday, January 7, 2020 - 14:05 Full Article
ule Delineating an extracellular redox-sensitive module in T-type Ca2+ channels [Membrane Biology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 T-type (Cav3) Ca2+ channels are important regulators of excitability and rhythmic activity of excitable cells. Among other voltage-gated Ca2+ channels, Cav3 channels are uniquely sensitive to oxidation and zinc. Using recombinant protein expression in HEK293 cells, patch clamp electrophysiology, site-directed mutagenesis, and homology modeling, we report here that modulation of Cav3.2 by redox agents and zinc is mediated by a unique extracellular module containing a high-affinity metal-binding site formed by the extracellular IS1–IS2 and IS3–IS4 loops of domain I and a cluster of extracellular cysteines in the IS1–IS2 loop. Patch clamp recording of recombinant Cav3.2 currents revealed that two cysteine-modifying agents, sodium (2-sulfonatoethyl) methanethiosulfonate (MTSES) and N-ethylmaleimide, as well as a reactive oxygen species–producing neuropeptide, substance P (SP), inhibit Cav3.2 current to similar degrees and that this inhibition is reversed by a reducing agent and a zinc chelator. Pre-application of MTSES prevented further SP-mediated current inhibition. Substitution of the zinc-binding residue His191 in Cav3.2 reduced the channel's sensitivity to MTSES, and introduction of the corresponding histidine into Cav3.1 sensitized it to MTSES. Removal of extracellular cysteines from the IS1–IS2 loop of Cav3.2 reduced its sensitivity to MTSES and SP. We hypothesize that oxidative modification of IS1–IS2 loop cysteines induces allosteric changes in the zinc-binding site of Cav3.2 so that it becomes sensitive to ambient zinc. Full Article
ule Structures of the MHC-I molecule BF2*1501 disclose the preferred presentation of an H5N1 virus-derived epitope [Protein Structure and Folding] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Lethal infections by strains of the highly-pathogenic avian influenza virus (HPAIV) H5N1 pose serious threats to both the poultry industry and public health worldwide. A lack of confirmed HPAIV epitopes recognized by cytotoxic T lymphocytes (CTLs) has hindered the utilization of CD8+ T-cell–mediated immunity and has precluded the development of effectively diversified epitope-based vaccination approaches. In particular, an HPAIV H5N1 CTL-recognized epitope based on the peptide MHC-I–β2m (pMHC-I) complex has not yet been designed. Here, screening a collection of selected peptides of several HPAIV strains against a specific pathogen-free pMHC-I (pBF2*1501), we identified a highly-conserved HPAIV H5N1 CTL epitope, named HPAIV–PA123–130. We determined the structure of the BF2*1501–PA123–130 complex at 2.1 Å resolution to elucidate the molecular mechanisms of a preferential presentation of the highly-conserved PA123–130 epitope in the chicken B15 lineage. Conformational characteristics of the PA123–130 epitope with a protruding Tyr-7 residue indicated that this epitope has great potential to be recognized by specific TCRs. Moreover, significantly increased numbers of CD8+ T cells specific for the HPAIV–PA123–130 epitope in peptide-immunized chickens indicated that a repertoire of CD8+ T cells can specifically respond to this epitope. We anticipate that the identification and structural characterization of the PA123–130 epitope reported here could enable further studies of CTL immunity against HPAIV H5N1. Such studies may aid in the development of vaccine development strategies using well-conserved internal viral antigens in chickens. Full Article
ule The rule of law and maritime security: understanding lawfare in the South China Sea By feedproxy.google.com Published On :: Wed, 04 Sep 2019 13:46:35 +0000 4 September 2019 , Volume 95, Number 5 Douglas Guilfoyle Read online Does the rule of law matter to maritime security? One way into the question is to examine whether states show a discursive commitment that maritime security practices must comply with international law. International law thus provides tools for argument for or against the validity of certain practices. The proposition is thus not only that international law matters to maritime security, but legal argument does too. In this article, these claims will be explored in relation to the South China Sea dispute. The dispute involves Chinese claims to enjoy special rights within the ‘nine-dash line’ on official maps which appears to lay claim to much of the South China Sea. Within this area sovereignty remains disputed over numerous islands and other maritime features. Many of the claimant states have engaged in island-building activities, although none on the scale of China. Ideas matter in such contests, affecting perceptions of reality and of what is possible. International law provides one such set of ideas. Law may be a useful tool in consolidating gains or defeating a rival's claims. For China, law is a key domain in which it is seeking to consolidate control over the South China Sea. The article places the relevant Chinese legal arguments in the context of China's historic engagement with the law of the sea. It argues that the flaw in China's approach has been to underestimate the extent to which it impinges on other states' national interests in the maritime domain, interests they conceptualize in legal terms. Full Article
ule Reimagining Trade Rules to Address Climate Change in a Post-Pandemic World By feedproxy.google.com Published On :: Fri, 24 Apr 2020 10:25:01 +0000 Webinar Research Event 5 May 2020 - 2:00pm to 3:00pm Event participants James Bacchus, Distinguished University Professor of Global Affairs and Director of the Center for Global Economic and Environmental Opportunity at the University of Central Florida; Member and Chair, WTO Appellate Body, 1995 - 2003Chair: Creon Butler, Director, Global Economy and Finance Programme, Chatham House This event is part of the Chatham House Global Trade Policy Forum and will take place virtually only.International trade has a crucial role to play in tackling climate change. The production and transport of goods is a major contributor to green-house gas emissions, as is the delivery of certain cross-border services. At the same time, it looks inevitable that the COVID-19 pandemic will lead to a radical re-think of global supply chains as companies and governments seek to build in greater resilience while at the same time preserving as far as possible the efficiency gains and lower costs that global supply chains generate when operating normally.Future international trade rules will have a crucial role to play in addressing both challenges; they represent both an opportunity and a risk. If designed well, they could play a very important role in re-enforcing moves towards a more sustainable use of resources, greater overall alignment of economies with the Paris Agreement, and greater economic resilience. But they could also, if poorly designed and implemented, or overly influenced by strategic political considerations, have significant unintended and negative implications. These include: reduced economic efficiency, increased poverty, unnecessary economic decoupling and reduced consensus on the broader mitigation and adaptation measures required to meet the challenge of climate change.Against this background, a number of key questions arise: In what areas, if any, do we need to modify or adapt key principles underlying the system of global trade rules in order to respond to the twin challenges of responding to climate change and building greater economic resilience? Which are the most promising/practical areas on which trade policy experts should focus now to re-launch/re-energize discussions on WTO reform, including, for example, dispute settlement? What national economic policies will be needed to complement the development of new/reformed trade disciplines in these areas? How might future political changes, such as a change in the US administration, affect the prospects for and political momentum behind such deliberations? What in any eventuality is the best way to build the required political momentum? This roundtable is convened by the Global Economy and Finance Programme and the US and the Americas Programme and it is part of the Chatham House Global Trade Policy Forum. The event will take place virtually only.We would like to take this opportunity to thank founding partner AIG and supporting partners Clifford Chance LLP, Diageo plc, and EY for their generous support of the Chatham House Global Trade Policy Forum.Please note this event is taking place between 2pm to 3pm BST. Department/project US and the Americas Programme, Global Trade Policy Forum Full Article
ule Don Berwick - you can break the rules to help patients By feeds.bmj.com Published On :: Fri, 15 Jun 2018 12:52:40 +0000 Don Berwick, president emeritus of the Institute of Healthcare Improvement, and former Administrator of the Centers for Medicare and Medicaid Services. In this conversation he discusses how he went from being a paediatrician to running Medicare for Obama, how we can create headroom in stressed systems, and breaking the rules to make things better... Full Article
ule Are the {beta}-Cell Signaling Molecules Malonyl-CoA and Cystolic Long-Chain Acyl-CoA Implicated in Multiple Tissue Defects of Obesity and NIDDM? By diabetes.diabetesjournals.org Published On :: 1996-03-01 Marc PrentkiMar 1, 1996; 45:273-283Original Article Full Article
ule 33 Trinidadians stranded in Barbados scheduled to return home By jamaica-gleaner.com Published On :: Tue, 21 Apr 2020 11:59:24 -0500 PORT OF SPAIN, Trinidad, CMC – Thirty three Trinidad and Tobago nationals who have been stranded in Barbados since March 23 are scheduled to return home on Tuesday. It’s reported that early Tuesday, National Security Minister... Full Article
ule Rule 5 pick Joe back in catcher's gear with Reds By mlb.mlb.com Published On :: Sun, 17 Feb 2019 19:05:55 EDT Utility player and Rule 5 selection Connor Joe has been working with the catchers since Reds Spring Training opened. What makes that a little more interesting is that Joe has never caught a game professionally. Full Article
ule Covid-19’s impact on US medical research—shifting money, easing rules By feeds.bmj.com Published On :: Friday, May 1, 2020 - 13:37 Full Article
ule Single-molecule level structural dynamics of DNA unwinding by human mitochondrial Twinkle helicase [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Knowledge of the molecular events in mitochondrial DNA (mtDNA) replication is crucial to understanding the origins of human disorders arising from mitochondrial dysfunction. Twinkle helicase is an essential component of mtDNA replication. Here, we employed atomic force microscopy imaging in air and liquids to visualize ring assembly, DNA binding, and unwinding activity of individual Twinkle hexamers at the single-molecule level. We observed that the Twinkle subunits self-assemble into hexamers and higher-order complexes that can switch between open and closed-ring configurations in the absence of DNA. Our analyses helped visualize Twinkle loading onto and unloading from DNA in an open-ringed configuration. They also revealed that closed-ring conformers bind and unwind several hundred base pairs of duplex DNA at an average rate of ∼240 bp/min. We found that the addition of mitochondrial single-stranded (ss) DNA–binding protein both influences the ways Twinkle loads onto defined DNA substrates and stabilizes the unwound ssDNA product, resulting in a ∼5-fold stimulation of the apparent DNA-unwinding rate. Mitochondrial ssDNA-binding protein also increased the estimated translocation processivity from 1750 to >9000 bp before helicase disassociation, suggesting that more than half of the mitochondrial genome could be unwound by Twinkle during a single DNA-binding event. The strategies used in this work provide a new platform to examine Twinkle disease variants and the core mtDNA replication machinery. They also offer an enhanced framework to investigate molecular mechanisms underlying deletion and depletion of the mitochondrial genome as observed in mitochondrial diseases. Full Article
ule Michigan coach Jim Harbaugh proposes major changes to NFL Draft eligibility rules By www.upi.com Published On :: Thu, 07 May 2020 19:41:19 -0400 Michigan coach Jim Harbaugh is urging the NFL and NCAA to amend their rules and provide flexibility to college football players who consider making the jump to the next level. Full Article
ule NFL releases dates, times for 2020 regular-season schedule By www.upi.com Published On :: Thu, 07 May 2020 21:15:24 -0400 The NFL revealed its 2020 regular-season schedule Thursday, with the Kansas City Chiefs kicking off their Super Bowl title defense against the Houston Texans in Week 1. Full Article
ule Korea's K-League soccer returns with rules against spitting, talking By www.upi.com Published On :: Fri, 08 May 2020 10:49:47 -0400 K-League soccer resumed with a game behind closed doors Friday in South Korea, with players prohibited from spitting and talking. Full Article
ule USCIS Fee Increase Proposed Rule Could Represent the Latest Step in Reshaping Immigration to United States By www.migrationpolicy.org Published On :: Thu, 19 Dec 2019 09:48:55 -0500 While much attention has been given to the move by U.S. Citizenship and Immigration Services to raise its application fees—including an 83 percent hike to apply for U.S. citizenship—the policy changes embedded in the proposed rule have been less scrutinized. The changes, including the elimination of most fee waivers for lower-income applicants, would likely reduce the number and shift the profile of those getting a green card or other immigration status. Full Article
ule ADA supports proposed rules to update federal Anti-Kickback Statute, Stark Law By www.ada.org Published On :: Mon, 06 Jan 2020 14:32:00 -0600 The American Dental Association supports a new safe harbor for cybersecurity technology and services and modifying the existing safe harbor for electronic health records to add protections for cybersecurity. This was in response to the Office of the Inspector General and Centers for Medicare & Medicaid Services’ proposed changes to the federal Anti-Kickback Statute and Stark Law exceptions. Full Article
ule ADA asks Treasury Department, Small Business Administration to clarify intent of interim rule By www.ada.org Published On :: Sun, 05 Apr 2020 11:09:00 -0500 The Association continues to wait for clear guidance from the U.S. Department of Treasury and Small Business Administration on the best way to help dentists considering applying for Paycheck Protection Program 7(a) loans and Economic Injury Disaster Loans. Full Article
ule CODA site visits rescheduled to 2021 due to COVID-19 By www.ada.org Published On :: Wed, 08 Apr 2020 09:20:00 -0500 The Commission on Dental Accreditation announced April 3 that it will reschedule all postponed and remaining site visits this year, including regular/reaccreditation and special focused site visits, to 2021 in response to the COVID-19 pandemic. Full Article
ule ADA advocates that third-party payers modify fee schedules as dentists consider going back to work By www.ada.org Published On :: Thu, 23 Apr 2020 14:19:00 -0500 The ADA is urging third-party payers to alter their fees to account for the increasing cost of personal protective equipment that dentists are using to protect themselves, their staff and patients. Full Article