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Legislation update: the Enterprise Act 2016 and the Concession Contracts Regulations 2016

Enterprise Bill 2016 On 4 May 2016, the Enterprise Act 2016 (“the Act”) received Royal Assent. The Act will be commenced in stages and has been enacted to help promote the growth of enterprise and small businesses within the UK. One of the main prov...




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Perpetuities and Accumulations Bill

It is proposed that the rule against perpetuities should no longer apply to property transactions, but only for those entered into after the law has changed.   A Perpetuities and Accumulations Bill has been published and underwent its second re...




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Interpreting American Public Opinion on International Trade: How Should Asia Respond?

By Marcus Noland HONOLULU (August 23, 2019)—For three generations, the United States championed a rules-based multilateral trading system. That stance was overturned by the election of an avowed protectionist, Donald Trump, as president. It would be understandable for Asians to wonder if this shift amounts to a permanent change in U.S. trade policy, and if so, how to proceed. Trump’s presidential campaign was notable in that it emphasized two issues—immigration and trade—that had seldom been in the forefront of U.S. presidential campaigns. But public opinion polls revealed that these issues were of growing importance to a sizeable number of voters whose preferences mirrored Trump’s protectionist positions.

This is a summary only. Click the title for the full article, or visit www.EastWestCenter.org/Research-Wire for more.




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Sykes Enterprises, Incorporated (SYKE) CEO Chuck Sykes on Q1 2020 Results - Earnings Call Transcript




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Cómo estudiar la Biblia: La interpretación

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.




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Cómo estudiar la Biblia: La interpretación B

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.




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Sykes Enterprises, Incorporated (SYKE) CEO Chuck Sykes on Q1 2020 Results - Earnings Call Transcript




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Enterprise Management Incentives

Good and bad news Yesterday, Chancellor Alistair Darling announced some changes to the Enterprise Management Incentive (EMI) legislation, which will impact on those companies operating EMI and those proposing to do so. The good news Under the cu...




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Disclosure of Beneficial Owners of Counterparties in Corporate Transactions

The Rules Governing the Securities on The Stock Exchange of Hong Kong Limited (the “Listing Rules”) impose certain disclosure obligations on listed issuers when they engage in different types of corporate transactions. However, it has be...




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Speed brief: Contractual interpretation

Supreme Court reinforces the need to interpret clauses by the words used and their "natural meaning" On 10 June 2015, the Supreme Court handed down judgment in the case of Arnold v Britton and others [2015] UKSC 36, which concerned the interpretatio...




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Shipping: York Antwerp Rules 2016

A new set of rules, the York Antwerp Rules 2016 (the “YAR 2016”) has been adopted by the Comité Maritime International.  They are based on the previous versions of the York Antwerp Rules (the “YAR”) with some nota...




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Shipping: the Privy Council’s interpretation of permissive language in arbitration clauses

Anzen Limited & Another v Hermes One Limited In the case of Anzen Limited v Hermes One Limited [2016] UKPC 1, the Privy Council considered the use of permissive language in an arbitration clause.  Specifically, the Council considered what o...




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Shipping: BIMCO launch new LNG voyage charterparty

On 6 April 2016, BIMCO and the International Group of Liquified Natural Gas (“LNG”) Importers (“GIIGNL”) jointly issued a standard form voyage charterparty designed for use in the LNG trade. Its introduction is said to be spe...




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Shipping: incorporation of time charterparty terms into a bill of lading

Reviewing the law and the impact on it of both the arguments in the Anna Bo [2015] 2 Lloyd’s Rep 578 and the Congenbill 2016 form The issue Bills of lading often include wording which purports to incorporate charterparty terms. Attempts to inc...




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Case C-260/17, Anodiki Services EPE: interpreting the scope of the “employment contracts” exemption under EU procurement legislation

Case C-260/17, Anodiki Services EPE1: interpreting the scope of the “employment contracts” exemption under EU procurement legislation Introduction The judgment relates to a request for a preliminary ruling made by Greece’s Council ...




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The Curse on the Serpent, Part 1




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The Curse on the Serpent, Part 2




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Kuwait- Interior Minister Al-Saleh calls Iraqi counterpart

(MENAFN - Kuwait News Agency (KUNA)) KUWAIT, May 9 (KUNA) -- Deputy Prime Minister, Minister of Interior and Minister of State for Cabinet Affairs Ana... ......




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Walking the Talk on Climate Change after the Pandemic: Reorienting State-Owned Enterprises towards Sustainability

Leonardo Beltran is Non-Resident Fellow of the Institute of the Americas, Member of the Board of SEforALL, and former Deputy Secretary at the Mexican Department of Energy

The post Walking the Talk on Climate Change after the Pandemic: Reorienting State-Owned Enterprises towards Sustainability appeared first on Inter Press Service.




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What surfing taught me about reforming state-owned enterprises -- by Rafael Abbasov

Reforming state-owned enterprises can be an extraordinarily complex activity but it is underpinned by a single clear goal.




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Building credit: How state-owned enterprises can get foreign financing for infrastructure -- by Donald Lambert

State-owned enterprises face unique challenges when it comes to attracting foreign financing for infrastructure projects. But there are solutions.




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Analog and Interface Treelink Products Presentation PowerPoint - Jan 15




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India: Micro, Small, and Medium Enterprise Development Project

The project aimed to improve access of micro, small, and medium enterprises (MSMEs) to commercial financing and market opportunities, thereby fostering growth, competitiveness, and employment creation in India. There were three targeted outputs. First was enhance credit delivery through Small Industries Development Bank of India (SIDBI) and participating financial institutions in the MSME subsector. Second was increased SME productive and managerial capacity and related new jobs created for new markets.




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How can a State-Owned Enterprise be eligible to bid for ADB projects?

This video defines State-Owned Enterprises (SOEs) and guides borrowers on how to assess their viability to participate as bidders under ADB funded projects.




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Driving Small and Medium-Sized Enterprise Participation in Global Value Chains: Evidence from India

Financial constraints are a significant barrier for India's SMEs participating in global value chains.




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Regulatory Frameworks for Reforms of State-Owned Enterprises in Thailand and Malaysia

Regulatory reforms should focus on building up market competition, which indirectly forces state-owned enterprises to improve their operation toward efficiency.




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Driving Small and Medium-Sized Enterprise Participation in Global Value Chains: Evidence from India

Financial constraints are a significant barrier for India's SMEs participating in global value chains.




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Regulatory Frameworks for Reforms of State-Owned Enterprises in Thailand and Malaysia

Regulatory reforms should focus on building up market competition, which indirectly forces state-owned enterprises to improve their operation toward efficiency.




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HARMAN and IBM Watson IoT Introduce Cognitive Rooms that Bring Connected Experiences to Enterprise Settings

HARMAN Professional Solutions and IBM (NYSE: IBM) Watson Internet of Things (IoT) today unveiled Voice-Enabled Cognitive Rooms. Using IBM's Watson artificial intelligence (AI) technology and HARMAN AKG microphones, JBL speakers and AMX AV control and ...




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Thousands of Amazon Shoppers Are Raving About This Palm-Sized Waterproof Speaker




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Your decision-making ability is a superpower physics can't explain

In a universe that unthinkingly follows the rules, human agency is an anomaly. Can physics ever make sense of our power to change the physical world at will?




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Reindeer's real superpowers could help us beat depression and cancer

So what if Rudolph can’t really fly? He and the herd have some truly amazing evolutionary adaptations that could inspire new treatments for human diseases




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Your decision-making ability is a superpower physics can't explain

In a universe that unthinkingly follows the rules, human agency is an anomaly. Can physics ever make sense of our power to change the physical world at will?




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Common herpes virus causes signs of Alzheimer's disease in brain cells

A study of brain cells in a dish adds to growing evidence that Alzheimer’s disease can be caused by herpes viruses, but antiviral treatment may help stop it




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Is Thyroid Hormone Dangerously Overprescribed in Older Patients?

Title: Is Thyroid Hormone Dangerously Overprescribed in Older Patients?
Category: Health News
Created: 4/1/2020 12:00:00 AM
Last Editorial Review: 4/2/2020 12:00:00 AM




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Caterpillar Invasion in London Puts People at Risk of Deadly Allergic Reactions

Title: Caterpillar Invasion in London Puts People at Risk of Deadly Allergic Reactions
Category: Health News
Created: 4/30/2018 12:00:00 AM
Last Editorial Review: 5/1/2018 12:00:00 AM




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Herpes Virus Yields Up Genetic Secrets

Title: Herpes Virus Yields Up Genetic Secrets
Category: Health News
Created: 4/29/2020 12:00:00 AM
Last Editorial Review: 4/30/2020 12:00:00 AM




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Development of a Dental School Strategic Plan to Inform Interprofessional Education

Changes in U.S. health care delivery systems and Commission on Dental Accreditation standards provide impetus for interprofessional education (IPE) and collaborative practice, but roadmaps for engaging dental and dental hygiene faculty to incorporate IPE in a systematic manner are limited. The purpose of this report is to describe the process for creating a strategy and gathering a variety of baseline data to use for determining objectives and metrics and the subsequent development of an IPE strategic plan at the University of North Carolina (UNC) at Chapel Hill Adams School of Dentistry (SOD). SOD IPE committee members included representation from the UNC Schools of Dentistry, Medicine, Pharmacy, and Business. A three-phase framework was developed. Phase 1 (IPE assessment) was an internal environmental scan including a 2017 faculty survey, departmental mapping of IPE activities, comparison of UNC with national results on the IPE component of the American Dental Education Association (ADEA) survey of dental school seniors (2016 graduating class), identification of faculty joint/adjunct appointments at other UNC schools, and a strengths, weaknesses, opportunities, threats (SWOT) analysis. Phase 2 (visioning) consisted of development of IPE mission, vision, and priorities. In Phase 3 (implementation), priorities were developed. Data-gathering led to a strategic plan with three objectives: 1) increase faculty engagement and recognition, 2) develop predoctoral dentistry and dental hygiene IPE curricula, and 3) develop an infrastructure that supports IPE. Specific initiatives and activities, supporting metrics, and estimated costs were developed for each objective. The framework guided a systematic, transparent, and organized process for collecting and monitoring the evidence and directing activities. A three-year strategic plan for IPE was developed in 2017, and implementation is ongoing.




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A Systematic Meta-Analysis of the Effect of Interprofessional Education on Health Professions Students Attitudes

Interprofessional education (IPE) is based on collaborative practices that increase the occasions for communication among those in various health professions. However, there is a paucity of literature about the effectiveness of IPE programs in health professions education. The aim of this systematic review and meta-analysis was to objectively assess the literature on the effectiveness of IPE in improving health professions students’ attitudes after training. The major scholarly databases were searched for relevant IPE studies involving predoctoral health professions students. Two independent researchers selected the studies, extracted the data, and assessed the quality of the studies. Meta-analyses of the outcomes were performed using random effects models. Sixteen articles were ultimately selected for detailed review and meta-analysis. The meta-analysis showed that IPE training had a significant influence on students’ understanding of collaboration and resulted in better attitudes about interprofessional teamwork. Subscale analysis showed that one subscale score (roles and responsibilities) did not statistically significantly improve after IPE training (p=0.06), whereas the other four subscale items showed statistically significant improvements (p<0.01). The test for overall effects showed that IPE training had a significantly positive influence on students’ attitudes about IPE (Z=6.85, p<0.01). Subgroup results showed that medical students had more positive attitudes about IPE than did dental students. Regardless of profession, women students responded with significantly more positive feedback than did men students (p=0.02). These results suggest that intervention through IPE training has had positive effects in health professions education. Gender was an important factor impacting the outcomes of IPE. However, further clinical practice interventions may be helpful to enhance the IPE competence of health professions students.




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Epistatic Interplay between Type IV Secretion Effectors Engages the Small GTPase Rab2 in the Brucella Intracellular Cycle

ABSTRACT

Intracellular bacterial pathogens remodel cellular functions during their infectious cycle via the coordinated actions of effector molecules delivered through dedicated secretion systems. While the function of many individual effectors is known, how they interact to promote pathogenesis is rarely understood. The zoonotic bacterium Brucella abortus, the causative agent of brucellosis, delivers effector proteins via its VirB type IV secretion system (T4SS) which mediate biogenesis of the endoplasmic reticulum (ER)-derived replicative Brucella-containing vacuole (rBCV). Here, we show that T4SS effectors BspB and RicA display epistatic interactions in Brucella replication. Defects in rBCV biogenesis and Brucella replication caused by deletion of bspB were dependent on the host GTPase Rab2a and suppressed by the deletion of ricA, indicating a role of Rab2-binding effector RicA in these phenotypic defects. Rab2a requirements for rBCV biogenesis and Brucella intracellular replication were abolished upon deletion of both bspB and ricA, demonstrating that the functional interaction of these effectors engages Rab2-dependent transport in the Brucella intracellular cycle. Expression of RicA impaired host secretion and caused Golgi fragmentation. While BspB-mediated changes in ER-to-Golgi transport were independent of RicA and Rab2a, BspB-driven alterations in Golgi vesicular traffic also involved RicA and Rab2a, defining BspB and RicA’s functional interplay at the Golgi interface. Altogether, these findings support a model where RicA modulation of Rab2a functions impairs Brucella replication but is compensated by BspB-mediated remodeling of Golgi apparatus-associated vesicular transport, revealing an epistatic interaction between these T4SS effectors.

IMPORTANCE Bacterial pathogens with an intracellular lifestyle modulate many host cellular processes to promote their infectious cycle. They do so by delivering effector proteins into host cells via dedicated secretion systems that target specific host functions. While the roles of many individual effectors are known, how their modes of action are coordinated is rarely understood. Here, we show that the zoonotic bacterium Brucella abortus delivers the BspB effector that mitigates the negative effect on bacterial replication that the RicA effector exerts via modulation of the host small GTPase Rab2. These findings provide an example of functional integration between bacterial effectors that promotes proliferation of pathogens.




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Sensory-Directed Genetic and Biochemical Characterization of Volatile Terpene Production in Kiwifruit

Terpene volatiles are found in many important fruit crops, but their relationship to flavor is poorly understood. Here, we demonstrate using sensory descriptive and discriminant analysis that 1,8-cineole contributes a key floral/eucalyptus note to the aroma of ripe 'Hort16A’ kiwifruit (Actinidia chinensis). Two quantitative trait loci (QTLs) for 1,8-cineole production were identified on linkage groups 27 and 29a in a segregating A. chinensis population, with the QTL on LG29a colocating with a complex cluster of putative terpene synthase (TPS)-encoding genes. Transient expression in Nicotiana benthamiana and analysis of recombinant proteins expressed in Escherichia coli showed four genes in the cluster (AcTPS1a–AcTPS1d) encoded functional TPS enzymes, which produced predominantly sabinene, 1,8-cineole, geraniol, and springene, respectively. The terpene profile produced by AcTPS1b closely resembled the terpenes detected in red-fleshed A. chinensis. AcTPS1b expression correlated with 1,8-cineole content in developing/ripening fruit and also showed a positive correlation with 1,8-cineole content in the mapping population, indicating the basis for segregation is an expression QTL. Transient overexpression of AcTPS1b in Actinidia eriantha fruit confirmed this gene produced 1,8-cineole in Actinidia. Structure-function analysis showed AcTPS1a and AcTPS1b are natural variants at key TPS catalytic site residues previously shown to change enzyme specificity in vitro. Together, our results indicate that AcTPS1b is a key gene for production of the signature flavor terpene 1,8-cineole in ripe kiwifruit. Using a sensory-directed strategy for compound identification provides a rational approach for applying marker-aided selection to improving flavor in kiwifruit as well as other fruits.




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Interleukin-1 Receptor-Associated Kinase (IRAK) Signaling in Kaposi Sarcoma-Associated Herpesvirus-Induced Primary Effusion Lymphoma [Virus-Cell Interactions]

Kaposi sarcoma-associated herpesvirus (KSHV) is necessary but not sufficient for primary effusion lymphoma (PEL) development. Alterations in cellular signaling pathways are also a characteristic of PEL. Other B cell lymphomas have acquired an oncogenic mutation in the myeloid differentiation primary response 88 (MYD88) gene. The MYD88 L265P mutant results in the activation of interleukin-1 receptor associated kinase (IRAK). To probe IRAK/MYD88 signaling in PEL, we employed CRISPR/Cas9 technology to generate stable deletion clones in BCBL-1Cas9 and BC-1Cas9 cells. To look for off-target effects, we determined the complete exome of the BCBL-1Cas9 and BC-1Cas9 cells. Deletion of either MYD88, IRAK4, or IRAK1 abolished interleukin-1 beta (IL-1β) signaling; however, we were able to grow stable subclones from each population. Transcriptome sequencing (RNA-seq) analysis of IRAK4 knockout cell lines (IRAK4 KOs) showed that the IRAK pathway induced cellular signals constitutively, independent of IL-1β stimulation, which was abrogated by deletion of IRAK4. Transient complementation with IRAK1 increased NF-B activity in MYD88 KO, IRAK1 KO, and IRAK4 KO cells even in the absence of IL-1β. IL-10, a hallmark of PEL, was dependent on the IRAK pathway, as IRAK4 KOs showed reduced IL-10 levels. We surmise that, unlike B cell receptor (BCR) signaling, MYD88/IRAK signaling is constitutively active in PEL, but that under cell culture conditions, PEL rapidly became independent of this pathway.

IMPORTANCE One hundred percent of primary effusion lymphoma (PEL) cases are associated with Kaposi sarcoma-associated herpesvirus (KSHV). PEL cell lines, such as BCBL-1, are the workhorse for understanding this human oncovirus and the host pathways that KSHV dysregulates. Understanding their function is important for developing new therapies as well as identifying high-risk patient groups. The myeloid differentiation primary response 88 (MYD88)/interleukin-1 receptor associated kinase (IRAK) pathway, which has progrowth functions in other B cell lymphomas, has not been fully explored in PEL. By performing CRISPR/Cas9 knockout (KO) studies targeting the IRAK pathway in PEL, we were able to determine that established PEL cell lines can circumvent the loss of IRAK1, IRAK4, and MYD88; however, the deletion clones are deficient in interleukin-10 (IL-10) production. Since IL-10 suppresses T cell function, this suggests that the IRAK pathway may serve a function in vivo and during early-stage development of PEL.




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Novel Insights into the Roles of Bcl-2 Homolog Nr-13 (vNr-13) Encoded by Herpesvirus of Turkeys in the Virus Replication Cycle, Mitochondrial Networks, and Apoptosis Inhibition [Virus-Cell Interactions]

The Bcl-2 (B cell lymphoma 2)-related protein Nr-13 plays a major role in the regulation of cell death in developing avian B cells. With over 65% sequence similarity to the chicken Nr-13, herpesvirus of turkeys (HVT) vNr-13, encoded by the HVT079 and HVT096 genes, is the first known alphaherpesvirus-encoded Bcl-2 homolog. HVT-infected cells were reported to be relatively more resistant to serum starvation, suggested that vNr-13 could be involved in protecting the cells. Here, we describe CRISPR/Cas9-based editing of exon 1 of the HVT079 and HVT096 genes from the HVT genome to generate the mutant HVT-vNr-13 to gain insights into its functional roles. Overall, wild-type HVT and HVT-vNr-13 showed similar growth kinetics; however, at early time points, HVT-vNr-13 showed 1.3- to 1.7-fold-lower growth of cell-associated virus and 3- to 6.2-fold-lower growth of cell-free virus. In transfected cells, HVT vNr-13 showed a mainly diffuse cytoplasmic distribution with faint nuclear staining. Further, vNr-13 localized to the mitochondria and endoplasmic reticulum (ER) and disrupted mitochondrial network morphology in the transfected cells. In the wild-type HVT-infected cells, vNr-13 expression appeared to be directly involved in the disruption of the mitochondrial network, as the mitochondrial network morphology was substantially restored in the HVT-vNr-13-infected cells. IncuCyte S3 real-time apoptosis monitoring demonstrated that vNr-13 is unequivocally involved in the apoptosis inhibition, and it is associated with an increase of PFU, especially under serum-free conditions in the later stages of the viral replication cycle. Furthermore, HVT blocks apoptosis in infected cells but activates apoptosis in noninfected bystander cells.

IMPORTANCE B cell lymphoma 2 (Bcl-2) family proteins play important roles in regulating apoptosis during homeostasis, tissue development, and infectious diseases. Several viruses encode homologs of cellular Bcl-2-proteins (vBcl-2) to inhibit apoptosis, which enable them to replicate and persist in the infected cells and to evade/modulate the immune response of the host. Herpesvirus of turkeys (HVT) is a nonpathogenic alphaherpesvirus of turkeys and chickens that is widely used as a live vaccine against Marek’s disease and as recombinant vaccine viral vectors for protecting against multiple avian diseases. Identical copies of the HVT genes HVT079 and HVT096 encode the Bcl-2 homolog vNr-13. While previous studies have identified the potential ability of vNr-13 in inhibiting apoptosis induced by serum deprivation, there have been no detailed investigations on the functions of vNr-13. Using CRISPR/Cas9-based ablation of the vNr-13 gene, we demonstrated the roles of HVT vNr-13 in early stages of the viral replication cycle, mitochondrial morphology disruption, and apoptosis inhibition in later stages of viral replication.




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SerpinB2 Regulates Immune Response in Kidney Injury and Aging

Background

Expression of SerpinB2, a regulator of inflammatory processes, has been described in the context of macrophage activation and cellular senescence. Given that mechanisms for these processes interact and can shape kidney disease, it seems plausible that SerpinB2 might play a role in renal aging, injury, and repair.

Methods

We subjected SerpinB2 knockout mice to ischemia-reperfusion injury or unilateral ureteral obstruction. We performed phagocyte depletion to study SerpinB2’s role beyond the effects of macrophages and transplanted bone marrow from knockout mice to wild-type mice and vice versa to dissect cell type–dependent effects. Primary tubular cells and macrophages from SerpinB2 knockout and wild-type mice were used for functional studies and transcriptional profiling.

Results

Cultured senescent tubular cells, kidneys of aged mice, and renal stress models exhibited upregulation of SerpinB2 expression. Functionally, lack of SerpinB2 in aged knockout mice had no effect on the magnitude of senescence markers but associated with enhanced kidney damage and fibrosis. In stress models, inflammatory cell infiltration was initially lower in knockout mice but later increased, leading to an accumulation of significantly more macrophages. SerpinB2 knockout tubular cells showed significantly reduced expression of the chemokine CCL2. Macrophages from knockout mice exhibited reduced phagocytosis and enhanced migration. Macrophage depletion and bone marrow transplantation experiments validated the functional relevance of these cell type–specific functions of SerpinB2.

Conclusions

SerpinB2 influences tubule-macrophage crosstalk by supporting tubular CCL2 expression and regulating macrophage phagocytosis and migration. In mice, SerpinB2 expression seems to be needed for coordination and timely resolution of inflammation, successful repair, and kidney homeostasis during aging. Implications of SerpinB2 in human kidney disease deserve further exploration.




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Closing the Brief Case: Mold Infection of an Indwelling Cranial Device--a Perplexing Combination of "Classic" Laboratory Findings [The Brief Case]




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The Brief Case: Mold Infection of an Indwelling Cranial Device--a Perplexing Combination of "Classic" Laboratory Findings [The Brief Case]




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Pathogen or Bystander: Clinical Significance of Detecting Human Herpesvirus 6 in Pediatric Cerebrospinal Fluid [Virology]

Human herpesvirus 6 (HHV-6) is an important cause of meningitis and meningoencephalitis. As testing for HHV-6 in cerebrospinal fluid (CSF) is more readily available using the FilmArray Meningitis/Encephalitis panel (FA-ME; BioFire Diagnostics, Salt Lake City, UT), we aimed to determine the clinical significance of detecting HHV-6 in order to identify true infections and to ensure appropriate antiviral initiation. Chart review on 25 patients positive for HHV-6 by FA-ME was performed to determine clinical presentation, comorbidity, treatment, and outcome. The presence of chromosomally integrated HHV-6 (ciHHV-6) DNA was also investigated. Of 1,005 children tested by FA-ME, HHV-6 was detected in 25 (2.5%). Five patients were diagnosed with either HHV-6 meningitis or meningoencephalitis based on HHV-6 detection in CSF, clinical presentation, and radiographic findings. Detection of HHV-6 by FA-ME led to discontinuation of acyclovir within 12.0 h in all 12 patients empirically treated with acyclovir. Six of the 12 patients were started on ganciclovir therapy within 6.8 h; 4 of these were treated specifically for HHV-6 infection, whereas therapy was discontinued in the remaining 2 patients. CSF parameters were not generally predictive of HHV-6 positivity. The presence of ciHHV-6 was confirmed in 3 of 18 patients who could be tested. Five of the 25 patients included in the study were diagnosed with HHV-6 meningitis/meningoencephalitis. FA-ME results led to discontinuation of empirical antiviral treatment in 12 patients and appropriate initiation of ganciclovir in 4 patients. In our institution, detection of HHV-6 using FA-ME led to faster establishment of disease etiology and optimization of antimicrobial therapy.




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Noncoding regions underpin avian bill shape diversification at macroevolutionary scales [RESEARCH]

Recent progress has been made in identifying genomic regions implicated in trait evolution on a microevolutionary scale in many species, but whether these are relevant over macroevolutionary time remains unclear. Here, we directly address this fundamental question using bird beak shape, a key evolutionary innovation linked to patterns of resource use, divergence, and speciation, as a model trait. We integrate class-wide geometric-morphometric analyses with evolutionary sequence analyses of 10,322 protein-coding genes as well as 229,001 genomic regions spanning 72 species. We identify 1434 protein-coding genes and 39,806 noncoding regions for which molecular rates were significantly related to rates of bill shape evolution. We show that homologs of the identified protein-coding genes as well as genes in close proximity to the identified noncoding regions are involved in craniofacial embryo development in mammals. They are associated with embryonic stem cell pathways, including BMP and Wnt signaling, both of which have repeatedly been implicated in the morphological development of avian beaks. This suggests that identifying genotype-phenotype association on a genome-wide scale over macroevolutionary time is feasible. Although the coding and noncoding gene sets are associated with similar pathways, the actual genes are highly distinct, with significantly reduced overlap between them and bill-related phenotype associations specific to noncoding loci. Evidence for signatures of recent diversifying selection on our identified noncoding loci in Darwin finch populations further suggests that regulatory rather than coding changes are major drivers of morphological diversification over macroevolutionary times.




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Recent advances in the application of mineral chemistry to exploration for porphyry copper-gold-molybdenum deposits: detecting the geochemical fingerprints and footprints of hypogene mineralization and alteration

In the past decade, significant research efforts have been devoted to mineral chemistry studies to assist porphyry exploration. These activities can be divided into two major fields of research: (1) porphyry indicator minerals (PIMs), which are used to identify the presence of, or potential for, porphyry-style mineralization based on the chemistry of magmatic minerals such as zircon, plagioclase and apatite, or resistate hydrothermal minerals such as magnetite; and (2) porphyry vectoring and fertility tools (PVFTs), which use the chemical compositions of hydrothermal minerals such as epidote, chlorite and alunite to predict the likely direction and distance to mineralized centres, and the potential metal endowment of a mineral district. This new generation of exploration tools has been enabled by advances in and increased access to laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), short-wave length infrared (SWIR), visible near-infrared (VNIR) and hyperspectral technologies. PIMs and PVFTs show considerable promise for exploration and are starting to be applied to the diversity of environments that host porphyry and epithermal deposits globally. Industry has consistently supported development of these tools, and in the case of PVFTs encouraged by several successful blind tests where deposit centres have successfully been predicted from distal propylitic settings. Industry adoption is steadily increasing but is restrained by a lack of the necessary analytical equipment and expertise in commercial laboratories, and also by the ongoing reliance on well-established geochemical exploration techniques (e.g. sediment, soil and rock chip sampling) that have aided the discovery of near-surface resources over many decades, but are now proving less effective in the search for deeply buried mineral resources and for those concealed under cover.

Thematic collection: This article is part of the Exploration 17 collection available at: https://www.lyellcollection.org/cc/exploration-17




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Fur-Dam Regulatory Interplay at an Internal Promoter of the Enteroaggregative Escherichia coli Type VI Secretion sci1 Gene Cluster [Article]

The type VI secretion system (T6SS) is a weapon for delivering effectors into target cells that is widespread in Gram-negative bacteria. The T6SS is a highly versatile machine, as it can target both eukaryotic and prokaryotic cells, and it has been proposed that T6SSs are adapted to the specific needs of each bacterium. The expression of T6SS gene clusters and the activation of the secretion apparatus are therefore tightly controlled. In enteroaggregative Escherichia coli (EAEC), the sci1 T6SS gene cluster is subject to a complex regulation involving both the ferric uptake regulator (Fur) and DNA adenine methylase (Dam)-dependent DNA methylation. In this study, an additional, internal, promoter was identified within the sci1 gene cluster using +1 transcriptional mapping. Further analyses demonstrated that this internal promoter is controlled by a mechanism strictly identical to that of the main promoter. The Fur binding box overlaps the –10 transcriptional element and a Dam methylation site, GATC-32. Hence, the expression of the distal sci1 genes is repressed and the GATC-32 site is protected from methylation in iron-rich conditions. The Fur-dependent protection of GATC-32 was confirmed by an in vitro methylation assay. In addition, the methylation of GATC-32 negatively impacted Fur binding. The expression of the sci1 internal promoter is therefore controlled by iron availability through Fur regulation, whereas Dam-dependent methylation maintains a stable ON expression in iron-limited conditions.

IMPORTANCE Bacteria use weapons to deliver effectors into target cells. One of these weapons, the type VI secretion system (T6SS), assembles a contractile tail acting as a spring to propel a toxin-loaded needle. Its expression and activation therefore need to be tightly regulated. Here, we identified an internal promoter within the sci1 T6SS gene cluster in enteroaggregative E. coli. We show that this internal promoter is controlled by Fur and Dam-dependent methylation. We further demonstrate that Fur and Dam compete at the –10 transcriptional element to finely tune the expression of T6SS genes. We propose that this elegant regulatory mechanism allows the optimum production of the T6SS in conditions where enteroaggregative E. coli encounters competing species.