pi CBD News: With the aim to encourage positive action for biodiversity and inspire others by showcasing the notable work of those it honours, nominations are now invited for the MIDORI Prize for Biodiversity 2016. The call for nominations remains open from By www.cbd.int Published On :: Mon, 15 Feb 2016 00:00:00 GMT Full Article
pi CBD News: Integral to the balance of nature, wildlife nurtures us with a sense of wonder and serves as a source of inspiration. By www.cbd.int Published On :: Tue, 01 Mar 2016 00:00:00 GMT Full Article
pi CBD News: Biodiversity - the diversity of life on Earth - underpins the natural resources that provide food and livelihoods throughout the world. For many women, biodiversity serves as the cornerstone of their work, their belief systems and their basic s By www.cbd.int Published On :: Wed, 02 Mar 2016 00:00:00 GMT Full Article
pi CBD News: Biological diversity underpins ecosystem functioning and the provisioning of ecosystem services essential for human well-being. By www.cbd.int Published On :: Mon, 04 Apr 2016 00:00:00 GMT Full Article
pi CBD News: Statement of the Executive Secretary of the Convention on Biological Diversity on the occasion of the Sustainable Ocean Initiative / Pacific Ocean Alliance Regional Workshop for the Pacific Islands, 31 October to 4 November 2016, Apia, Samoa By www.cbd.int Published On :: Mon, 31 Oct 2016 00:00:00 GMT Full Article
pi CBD News: Statement of the Executive Secretary of the Convention on Biological Diversity on the occasion of the Fifty-Second Session of the International Tropical Timber Council and Associated Sessions of the Committees, 10 November 2016, Yokohama, Japan By www.cbd.int Published On :: Thu, 10 Nov 2016 00:00:00 GMT Full Article
pi CBD News: We, the Heads of State/Government of Brunei Darussalam, the Kingdom of Cambodia, the Republic of Indonesia, the Lao People's Democratic Republic, Malaysia, the Republic of the Union of Myanmar, the Republic of the Philippines, the Republic o By www.cbd.int Published On :: Mon, 19 Dec 2016 00:00:00 GMT Full Article
pi CBD News: On behalf of the Executive Secretary of the Convention on Biological Diversity, Dr. Cristiana Pa?ca Palmer, I would like to welcome you to the "Capacity building workshop for Caribbean Small Island Developing States towards achieving Aichi By www.cbd.int Published On :: Mon, 18 Sep 2017 00:00:00 GMT Full Article
pi CBD News: Biodiversity underpins ecosystem functioning and the provisioning of ecosystem services essential for human well-being. By www.cbd.int Published On :: Mon, 29 Jan 2018 00:00:00 GMT Full Article
pi CBD News: For this year's International Women's Day, I join my voice to the call to action to empower women in all settings, rural and urban, and to draw inspiration from the activists working to achieve women's rights and gender equality. By www.cbd.int Published On :: Thu, 08 Mar 2018 00:00:00 GMT Full Article
pi CBD News: The ecologically or biologically significant marine areas (EBSA) booklet series provide snapshot summaries of the pages upon pages of data compiled by participating experts, to provide an inspiring overview of some of the most ecologically or bi By www.cbd.int Published On :: Fri, 22 Jun 2018 00:00:00 GMT Full Article
pi CBD News: Inspired by discussions on the possibilities of transformational change, a keynote address by Canadian astronaut Roberta Bondar, and a celebration of indigenous culture, more than 1,000 delegates from around the world concluded two critical meet By www.cbd.int Published On :: Wed, 18 Jul 2018 00:00:00 GMT Full Article
pi CBD News: Germany has published the first report on the utilization of genetic resources through the Access and Benefit-sharing (ABS) Clearing-House by issuing a checkpoint communiqué concerning research on ants from South Africa. This was rapidly fo By www.cbd.int Published On :: Thu, 02 Aug 2018 00:00:00 GMT Full Article
pi CBD News: The inaugural Nature Champions Summit closed Thursday with a call to put nature at the centre of the global discourse together with climate action and sustainable development. By www.cbd.int Published On :: Mon, 29 Apr 2019 00:00:00 GMT Full Article
pi CBD News: Two major pieces of research reveal the clear and present danger biodiversity loss and climate change pose to the health, security and well-being of humanity. By news.trust.org Published On :: Thu, 19 Sep 2019 00:00:00 GMT Full Article
pi CBD News: In the "Beijing Call for Biodiversity Conservation and Climate Change", French President Emmanuel Macron and Chinese President Xi Jinping on 6 November reaffirmed their commitments to enhance international cooperation on climate change By www.diplomatie.gouv.fr Published On :: Thu, 07 Nov 2019 00:00:00 GMT Full Article
pi CBD Notification SCBD/SSSF/AS/ML/GD/88414 (2019-114): Tracking Economic Instruments and Finance for Biodiversity: Invitation to contribute data on positive incentives relevant to Aichi Biodiversity Target 3 to the OECD PINE database By www.cbd.int Published On :: Thu, 12 Dec 2019 00:00:00 GMT Full Article
pi CBD Notification SCBD/IMS/JMF/NVW/86292 (2019-117): Follow-up invitation to participate in and/or contribute to the piloting and further development of a methodology for the voluntary peer review of national biodiversity strategies and action plans By www.cbd.int Published On :: Wed, 18 Dec 2019 00:00:00 GMT Full Article
pi High order explicit local time stepping methods for hyperbolic conservation laws By www.ams.org Published On :: Tue, 07 Apr 2020 14:09 EDT Thi-Thao-Phuong Hoang, Lili Ju, Wei Leng and Zhu Wang Math. Comp. 89 (2020), 1807-1842. Abstract, references and article information Full Article
pi CapitalRise reassesses its mission amidst Brexit and regulation change By www.techworld.com Published On :: Mon, 23 Mar 2020 08:50:00 GMT The proptech startup wanted to democratise investment in prime real estate projects through crowdfunding, but government regulations have limited its reach to high net worth individuals Full Article
pi How are UK tech startups helping fight coronavirus? By www.techworld.com Published On :: Wed, 01 Apr 2020 07:00:00 GMT Health startups are being corralled by the NHS and the government to point their talents at the COVID-19 pandemic, while others are volunteering services to help stymie the spread of the infectious new disease Full Article
pi FCA delays two-factor online shopping authentication by 6 months By www.techworld.com Published On :: Fri, 01 May 2020 07:50:00 GMT The new rule, which will force payments platforms and online retailers to strongly authenticate purchases of £28 or more has been delayed by another six months amidst the COVID-19 pandemic Full Article
pi Uniqueness for the inverse boundary value problem of piecewise homogeneous anisotropic elasticity in the time domain By www.ams.org Published On :: Wed, 08 Apr 2020 11:21 EDT Cătălin I. Cârstea, Gen Nakamura and Lauri Oksanen Trans. Amer. Math. Soc. 373 (2020), 3423-3443. Abstract, references and article information Full Article
pi Fun Raspberry Pi projects for beginners By www.techworld.com Published On :: Thu, 16 Jan 2020 12:00:00 GMT Full Article
pi Who are the UK's best venture capital firms? By www.techworld.com Published On :: Fri, 17 Jan 2020 14:00:00 GMT Full Article
pi Detecting mapping spaces By www.ams.org Published On :: Thu, 02 Apr 2020 13:59 EDT Alyson Bittner Proc. Amer. Math. Soc. 148 (2020), 2683-2693. Abstract, references and article information Full Article
pi 1st eigenvalue pinching for convex hypersurfaces in a Riemannian manifold By www.ams.org Published On :: Thu, 02 Apr 2020 13:59 EDT Yingxiang Hu and Shicheng Xu Proc. Amer. Math. Soc. 148 (2020), 2609-2615. Abstract, references and article information Full Article
pi The Ricci pinching functional on solvmanifolds II By www.ams.org Published On :: Thu, 02 Apr 2020 13:59 EDT Jorge Lauret and Cynthia E. Will Proc. Amer. Math. Soc. 148 (2020), 2601-2607. Abstract, references and article information Full Article
pi Refined scales of decaying rates of operator semigroups on Hilbert spaces: Typical behavior By www.ams.org Published On :: Thu, 02 Apr 2020 13:59 EDT Moacir Aloisio, Silas L. Carvalho and César R. de Oliveira Proc. Amer. Math. Soc. 148 (2020), 2509-2523. Abstract, references and article information Full Article
pi Basic Law underpins HK’s success By www.news.gov.hk Published On :: Sat, 04 Apr 2020 00:00:00 +0800 On April 4, 1990, the Basic Law of the Hong Kong Special Administrative Region of the People’s Republic of China was adopted by the Seventh National People’s Congress (NPC) of the People’s Republic of China (PRC). The Basic Law enshrines the basic policies of the PRC regarding the Hong Kong Special Administrative Region (HKSAR) and provides a solid constitutional basis for the implementation of “one country, two systems”. Looking back, we must not forget the purpose and mission of the Basic Law. The Basic Law clearly states that Hong Kong has been part of the territory of China since ancient times and is an inalienable part of the PRC. It is a Special Administrative Region enjoying a high degree of autonomy under the Central People’s Government. Upholding national unity and territorial integrity, maintaining the prosperity and stability of Hong Kong, and taking account of history and realities, the “one country, two systems” principle was put forth by Mr Deng Xiaoping as a way to preserve the characteristics and strengths of Hong Kong as much as possible and to enable Hong Kong citizens to maintain their way of life. In the 22 years since her return to the motherland, Hong Kong has weathered different challenges and, on the whole, the implementation of “one country, two systems” has been successful. Leveraging on our strengths in free market economy, rule of law, independent judiciary and the free flow of information and with our country’s strong support, Hong Kong has developed into an international financial, trade and transportation centre and attracted more than 9,000 overseas and Mainland companies to establish offices here, with many of them making Hong Kong as their regional headquarters in Asia-Pacific. International financial centreArticle 109 of the Basic Law confirms Hong Kong’s status as an international financial centre and stipulates that the Government of the Hong Kong Special Administrative Region shall provide an appropriate economic and legal environment for the maintenance of such status. Specifically, under the Basic Law: - The Hong Kong dollar is the legal tender of the HKSAR and the linked exchange rate system has been maintained. With the strong support of the Central Government, Hong Kong has been able to maintain financial stability even during turbulent times. Riding on our country’s reform and opening up, Hong Kong has also developed into the world’s largest offshore renminbi centre. - The free flow of capital is protected and has attracted a large number of foreign direct investment and companies using Hong Kong as an ideal platform for initial public offerings and fundraising. Over the past 10 years, Hong Kong has topped the annual global IPO rankings six times. - Hong Kong maintains a simple and low tax system, which is key to Hong Kong’s success as an international financial, trading and business centre. The Hong Kong Special Administrative Region Government is free to implement tax measures according to policy needs under its independent tax system. Since I took office, I have put in place initiatives such as the two-tier profits tax system and tax deduction for research and development expenditure to enhance Hong Kong’s competitiveness. Rule of law and independent judiciaryThe Basic Law preserves and guarantees Hong Kong’s long-established and trusted common law system and allows the HKSAR to enjoy independent judicial power, including that of final adjudication. The rule of law and an independent judiciary, which are held dearly by Hong Kong people, are constitutionally protected. The Basic Law stipulates that judges shall be appointed by the Chief Executive on the recommendation of an independent commission; for the appointment of judges of the Court of Final Appeal (CFA) and the Chief Judge of the High Court, the Chief Executive shall obtain the endorsement of the Legislative Council and report such appointment to the Standing Committee of the NPC for the record. Last month, I accepted the recommendation of the Judicial Officers Recommendation Commission to appoint the Honourable Justice Andrew Cheung, Permanent Judge of the CFA, to succeed The Honourable Chief Justice Geoffrey Ma who will retire next year. The Basic Law also allows the CFA to draw on the experience of judges from other common law jurisdictions. Currently, 15 eminent judges from the United Kingdom, Australia and Canada are sitting on the CFA as non-permanent judges. Their participation shows that our rule of law and independent judiciary are well recognised. Rights and freedoms of residentsThe fundamental rights and freedoms of Hong Kong residents are fully protected by the Basic Law. Under Chapter 3, Hong Kong residents shall have freedom of speech, of the press and of publication; freedom of association, of assembly, of procession and of demonstration; freedom of the person; freedom of communication; freedom of religious belief; freedom of choice of occupation; freedom to engage in academic research, literary and artistic creation, and other cultural activities; freedom of marriage and so forth. However, as pointed out by our courts in their judgments, freedom is not absolute; one should respect the rights and freedoms of other people and be subject to law when exercising such freedoms. Developing external affairsHong Kong has always been a bridge between the East and the West. The Basic Law allows the HKSAR to maintain and develop relations with foreign states and regions and relevant international organisations in the appropriate fields, including economic, trade, financial and monetary, shipping, communications, tourism, cultural and sports fields on its own, using the name Hong Kong, China. The HKSAR has participated in the World Trade Organization, the World Meteorological Organization, the Asia-Pacific Economic Cooperation and many others in the name Hong Kong, China and has entered into hundreds of bilateral agreements with other countries, including Free Trade Agreements, Investment Promotion & Protection Agreements and Comprehensive Double Taxation Agreements. Hong Kong athletes can also represent Hong Kong in international competitions. The implementation of “one country, two systems” fully demonstrates that it is the best institutional arrangement to maintain Hong Kong’s long-term prosperity and stability. As a pioneering initiative, its application entails an evolving process and we have to effectively and fully apply this principle in order to maintain the prosperity and stability of Hong Kong, to meet the aspirations of our citizens and to meet the fundamental interests of our country. I encourage all Hong Kong citizens to learn more about the Basic Law, including the institutional safeguards, and the rights and duties of Hong Kong residents. In so doing, we should consider how best we can continue to leverage on Hong Kong’s advantages, allowing Hong Kong to advance with the country and enabling every Hong Kong resident to realise their goal. Chief Executive Carrie Lam wrote this op-ed entitled The Basic Law - Best Safeguard for the Prosperity & Stability of Hong Kong on April 4. Full Article
pi Anti-epidemic fund committee meets By www.news.gov.hk Published On :: Mon, 20 Apr 2020 00:00:00 +0800 Chief Secretary Matthew Cheung today chaired the fourth meeting of the Anti-epidemic Fund Steering Committee, during which the funding commitment for 33 measures under the second-round of the fund was approved. The Legislative Council Finance Committee last Saturday approved a funding application of $137.5 billion, including an injection of $120.5 billion to the Anti-epidemic Fund to roll out the second round of measures to provide further assistance or relief to the public and enterprises hard hit by the current epidemic or affected by anti-epidemic measures. Mr Cheung said: "The pandemic has caused an unprecedented impact on Hong Kong's economy and various sectors have been hard hit. “The Government will take resolute and unprecedented measures to expeditiously relieve the imminent needs of the businesses and members of the public. "To provide assistance and relief to relevant enterprises and members of the public as soon as possible, I have asked the bureaus and departments to implement the measures at full steam to address the pressing needs of the community promptly and achieve the effect of safeguarding jobs and supporting enterprises." Separately, the Education Bureau said the Finance Committee’s approval of the funding application for the second round of the fund and other relief measures included a one-off interest-free deferral of loan repayment for two years to self-financing post-secondary institutions under the Start-up Loan Scheme, non-profit-making international schools and student loan repayers. All borrowers of the Tertiary Student Finance Scheme - Publicly-funded Programmes, Financial Assistance Scheme for Post-secondary Students, Non-means-tested Loan Scheme for Full-time Tertiary Students, Non-means-tested Loan Scheme for Post-secondary Students and Extended Non-means-tested Loan Scheme will be offered an interest-free deferral of loan repayment from April 1 this year to March 31, 2022, including their loan instalments and interests. The annual administrative fee of $180 charged on the non-means-tested loan repayers during the suspension period will be waived. The risk-adjusted-factor rate for setting the interest rate will also be maintained at zero. Additionally, support for the construction sector will be enhanced. The Development Bureau today said a one-off subsidy of $7,500 will be offered to each eligible construction worker. More than 530,000 workers will benefit from the subsidy, including workers of construction sites as well as those registered under the Electrical & Mechanical Services Department, the Buildings Department, the Water Supplies Department and the Fire Services Department. At the same time, a one-off subsidy will be provided to 30,000 construction-related enterprises, generally small-scaled, which cannot benefit from the first round of the Anti-epidemic Fund. Each eligible contractor, specialist contractor, works contractor and supplier can receive a one-off subsidy of $20,000, while minor works contractors, registered contractors of electrical, gas, lift, escalator and fire service installation along with suppliers of construction-related machinery and equipment rental can receive $10,000 each. About 600 consultant firms offering engineering, architectural and related professional services will receive a subsidy of $50,000 each to support professionals in the sector. The Government will also provide a direct subsidy of $3 million to each non-profit-making organisation running the 10 projects under the Revitalising Historic Buildings Through Partnership Scheme, PMQ and the Energizing Kowloon East - Fly the Flyover Operation. Full Article
pi The Pathophysiology of Cardiovascular Disease and Diabetes: Beyond BloodPressure and Lipids By spectrum.diabetesjournals.org Published On :: 2008-07-01 Betsy B. DokkenJul 1, 2008; 21:160-165From Research to Practice/Cardiovascular Disease and Diabetes Full Article
pi Detection, Prevention, and Treatment of Hypoglycemia in the Hospital By spectrum.diabetesjournals.org Published On :: 2005-01-01 Donna TomkyJan 1, 2005; 18:39-44Articles Full Article
pi Anti-epidemic fund committee meets By www.news.gov.hk Published On :: Wed, 06 May 2020 00:00:00 +0800 Chief Secretary Matthew Cheung today chaired the Anti-epidemic Fund Steering Committee's fifth meeting to examine the implementation progress of the host of measures launched under the fund. The committee noted the details of over 20 second-round relief measures have been announced since the Legislative Council Finance Committee approved the $120.5 billion injection to the fund on April 18. Other measures will be launched as soon as possible to provide timely relief to the affected sectors and individuals. The committee also noted that the fund has paid out over $13 billion, and many businesses and members of the public have gradually received subsidies. Mr Cheung said the measures aim to preserve employment and assist the self-employed, provide additional relief to those sectors hard hit by the pandemic and pave the way for the post-pandemic economic recovery. “We will continue to process applications and disburse subsidies as soon as possible to help businesses and members of the public tackle the challenges caused by the pandemic and to support enterprises, safeguard jobs and relieve people’s burden," he stressed. For the Retail Sector Subsidy Scheme which provides a one-off subsidy of $80,000 to eligible retailers, about 93,000 applications were received. The committee was pleased to note that the scheme has been disbursing subsidies progressively and over $2.7 billion in subsidies have been approved so far, involving about 33,000 applications. Full Article
pi "The AMS and Science Policy," a Capital Currents blog post by Karen Saxe By www.ams.orghttps Published On :: Thu, 23 Apr 2020 00:00:00 EST Full Article
pi Geometry of Isotropic Convex Bodies By www.ams.org Published On :: Silouanos Brazitikos and Apostolos Giannopoulos, University of Athens, Petros Valettas, Texas A & M University, and Beatrice-Helen Vritsiou, University of Athens - AMS, 2014, 594 pp., Hardcover, ISBN-13: 978-1-4704-1456-6, List: US$134, All AMS Members: US$107.20, SURV/196 The study of high-dimensional convex bodies from a geometric and analytic point of view, with an emphasis on the dependence of various parameters on... Full Article
pi Three NSF RAPID grants to develop quicker test for COVID-19 for Holonyak Lab faculty By www.eurekalert.org Published On :: Wed, 06 May 2020 00:00:00 EDT (University of Illinois Grainger College of Engineering) Three Nick Holonyak Jr., Micro and Nanotechnology Lab (HMNTL) faculty members received NSF Rapid Response Research (RAPID) program grants, all of which aim to shorten the amount of time it takes to process a COVID-19 test with less false negatives. Current tests can take as long as five days for results to be. Full Article
pi Some anti-epidemic measures eased By www.news.gov.hk Published On :: Tue, 05 May 2020 00:00:00 +0800 (To watch the full press conference with sign language interpretation, click here.) Chief Executive Carrie Lam today said because Hong Kong has not reported a local COVID-19 case for over two weeks and imported cases are low, some anti-epidemic measures can be lifted. During a press conference, Mrs Lam outlined that unlike some European countries, Hong Kong did not need to go into lockdown to contain the spread of the disease. “Hong Kong has never gone into a stage of a complete city lockdown. In some of the European countries where they practise a city lockdown, residents are simply not allowed to leave their homes, except for some very essential purposes. But we have never adopted that practice. “And in fact, many renowned experts are now trying to study our situation - why does Hong Kong succeed in keeping the confirmed cases at a low level without drastic measures like a complete city lockdown. And I do think that is a very interesting topic for further research.” Mrs Lam noted that the Government had adopted the “suppress and lift” strategy under which restrictions are implemented and lifted in accordance with the infection situation. “The strategy that Hong Kong has been adopting - and advocated by some of our experts - is what we call a ‘suppress and lift strategy’. “So in light of the number of confirmed cases and likelihood of the spread of the disease in the community, we will have to suppress in order to make sure that there will be no surge in the number of confirmed cases as we have seen in some neighbouring regions. “When the situation of the infection stabilises, that is the time for lifting, that is, loosening a bit so that society can operate more normally, especially for the businesses and for individuals’ behaviour.” The Chief Executive said the Government still needed to monitor the COVID-19 situation closely, even though it was in the stage of lifting restrictions. “We are now right in the stage of lifting because we have not had a local case for 16 days already and the number of imported cases is very, very low. “We are now quite confident that the system of testing and holding that we have put in place for all arrivals from overseas would enable us to control the number of imported cases. So this is a time for lifting and this afternoon we have announced a number of lifting measures. “If the situation continues to stay at the current level - no local cases, very few imported cases - then at the end of the 14-day period, that is May 22, of course that would be the time for more relaxation.” Mrs Lam added that if a local case suddenly surfaced, Hong Kong may have to go back to some suppression measures, which was why the Government had to monitor the situation closely so it could take the necessary and pertinent response measures. Full Article
pi Hospital discharge criteria explained By www.news.gov.hk Published On :: Thu, 07 May 2020 00:00:00 +0800 (To watch the full press briefing with sign language interpretation, click here.) The Centre for Health Protection today said recovered COVID-19 patients or those who did not have any symptoms may be discharged from hospital 10 days after the onset of symptoms or a positive test result. Its Communicable Disease Branch Head Dr Chuang Shuk-kwan told a press briefing that the revised discharge criteria was based on the latest scientific evidence. “Our Scientific Committee on Emerging & Zoonotic Diseases met yesterday and examined the latest scientific evidence on whether the virus will be viable from a patient. “And the available evidence showed that this virus is usually not detected after 10 days since the onset of symptoms of patients. Some patients may have persistent positive PCR (polymerase chain reaction) for a long period of time.” Dr Chuang noted that patients still had to meet the criteria of having two clinical specimens test negative, or testing positive for the SARS-CoV-2 antibody to be discharged. “We have revised the discharge criteria to include the patient who (must have) been staying in the hospital for at least 10 days after the onset of symptoms. So this is the additional criteria, in addition to the previous criteria of two consecutive negative specimens. “We added another criteria (which is) in case a patient has stayed in the hospital for a long time, more than 10 days since the onset of symptoms, but he or she has persistent positive PCR despite the Ct (cycle threshold) value being very high, they can check their serology, the antibody. So if the antibody turns positive, usually it is after 10 days, then he or she can be discharged. “So this is based on the latest scientific evidence.” Full Article
pi A comprehensive evaluation of a typical plant telomeric G-quadruplex (G4) DNA reveals the dynamics of G4 formation, rearrangement, and unfolding [Plant Biology] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 Telomeres are specific nucleoprotein structures that are located at the ends of linear eukaryotic chromosomes and play crucial roles in genomic stability. Telomere DNA consists of simple repeats of a short G-rich sequence: TTAGGG in mammals and TTTAGGG in most plants. In recent years, the mammalian telomeric G-rich repeats have been shown to form G-quadruplex (G4) structures, which are crucial for modulating telomere functions. Surprisingly, even though plant telomeres are essential for plant growth, development, and environmental adaptions, only few reports exist on plant telomeric G4 DNA (pTG4). Here, using bulk and single-molecule assays, including CD spectroscopy, and single-molecule FRET approaches, we comprehensively characterized the structure and dynamics of a typical plant telomeric sequence, d[GGG(TTTAGGG)3]. We found that this sequence can fold into mixed G4s in potassium, including parallel and antiparallel structures. We also directly detected intermediate dynamic transitions, including G-hairpin, parallel G-triplex, and antiparallel G-triplex structures. Moreover, we observed that pTG4 is unfolded by the AtRecQ2 helicase but not by AtRecQ3. The results of our work shed light on our understanding about the existence, topological structures, stability, intermediates, unwinding, and functions of pTG4. Full Article
pi Cell-specific expression of the transcriptional regulator RHAMM provides a timing mechanism that controls appropriate wound re-epithelialization [Glycobiology and Extracellular Matrices] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 Prevention of aberrant cutaneous wound repair and appropriate regeneration of an intact and functional integument require the coordinated timing of fibroblast and keratinocyte migration. Here, we identified a mechanism whereby opposing cell-specific motogenic functions of a multifunctional intracellular and extracellular protein, the receptor for hyaluronan-mediated motility (RHAMM), coordinates fibroblast and keratinocyte migration speed and ensures appropriate timing of excisional wound closure. We found that, unlike in WT mice, in Rhamm-null mice, keratinocyte migration initiates prematurely in the excisional wounds, resulting in wounds that have re-surfaced before the formation of normal granulation tissue, leading to a defective epidermal architecture. We also noted aberrant keratinocyte and fibroblast migration in the Rhamm-null mice, indicating that RHAMM suppresses keratinocyte motility but increases fibroblast motility. This cell context–dependent effect resulted from cell-specific regulation of extracellular signal-regulated kinase 1/2 (ERK1/2) activation and expression of a RHAMM target gene encoding matrix metalloprotease 9 (MMP-9). In fibroblasts, RHAMM promoted ERK1/2 activation and MMP-9 expression, whereas in keratinocytes, RHAMM suppressed these activities. In keratinocytes, loss of RHAMM function or expression promoted epidermal growth factor receptor–regulated MMP-9 expression via ERK1/2, which resulted in cleavage of the ectodomain of the RHAMM partner protein CD44 and thereby increased keratinocyte motility. These results identify RHAMM as a key factor that integrates the timing of wound repair by controlling cell migration. Full Article
pi 12-LOX catalyzes the oxidation of 2-arachidonoyl-lysolipids in platelets generating eicosanoid-lysolipids that are attenuated by iPLA2{gamma} knockout [Signal Transduction] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 The canonical pathway of eicosanoid production in most mammalian cells is initiated by phospholipase A2-mediated release of arachidonic acid, followed by its enzymatic oxidation resulting in a vast array of eicosanoid products. However, recent work has demonstrated that the major phospholipase in mitochondria, iPLA2γ (patatin-like phospholipase domain containing 8 (PNPLA8)), possesses sn-1 specificity, with polyunsaturated fatty acids at the sn-2 position generating polyunsaturated sn-2-acyl lysophospholipids. Through strategic chemical derivatization, chiral chromatographic separation, and multistage tandem MS, here we first demonstrate that human platelet-type 12-lipoxygenase (12-LOX) can directly catalyze the regioselective and stereospecific oxidation of 2-arachidonoyl-lysophosphatidylcholine (2-AA-LPC) and 2-arachidonoyl-lysophosphatidylethanolamine (2-AA-LPE). Next, we identified these two eicosanoid-lysophospholipids in murine myocardium and in isolated platelets. Moreover, we observed robust increases in 2-AA-LPC, 2-AA-LPE, and their downstream 12-LOX oxidation products, 12(S)-HETE-LPC and 12(S)-HETE-LPE, in calcium ionophore (A23187)-stimulated murine platelets. Mechanistically, genetic ablation of iPLA2γ markedly decreased the calcium-stimulated production of 2-AA-LPC, 2-AA-LPE, and 12-HETE-lysophospholipids in mouse platelets. Importantly, a potent and selective 12-LOX inhibitor, ML355, significantly inhibited the production of 12-HETE-LPC and 12-HETE-LPE in activated platelets. Furthermore, we found that aging is accompanied by significant changes in 12-HETE-LPC in murine serum that were also markedly attenuated by iPLA2γ genetic ablation. Collectively, these results identify previously unknown iPLA2γ-initiated signaling pathways mediated by direct 12-LOX oxidation of 2-AA-LPC and 2-AA-LPE. This oxidation generates previously unrecognized eicosanoid-lysophospholipids that may serve as biomarkers for age-related diseases and could potentially be used as targets in therapeutic interventions. Full Article
pi 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
pi Structural insight into the recognition of pathogen-derived phosphoglycolipids by C-type lectin receptor DCAR [Protein Structure and Folding] By www.jbc.org Published On :: 2020-04-24T06:08:45-07:00 The C-type lectin receptors (CLRs) form a family of pattern recognition receptors that recognize numerous pathogens, such as bacteria and fungi, and trigger innate immune responses. The extracellular carbohydrate-recognition domain (CRD) of CLRs forms a globular structure that can coordinate a Ca2+ ion, allowing receptor interactions with sugar-containing ligands. Although well-conserved, the CRD fold can also display differences that directly affect the specificity of the receptors for their ligands. Here, we report crystal structures at 1.8–2.3 Å resolutions of the CRD of murine dendritic cell-immunoactivating receptor (DCAR, or Clec4b1), the CLR that binds phosphoglycolipids such as acylated phosphatidyl-myo-inositol mannosides (AcPIMs) of mycobacteria. Using mutagenesis analysis, we identified critical residues, Ala136 and Gln198, on the surface surrounding the ligand-binding site of DCAR, as well as an atypical Ca2+-binding motif (Glu-Pro-Ser/EPS168–170). By chemically synthesizing a water-soluble ligand analog, inositol-monophosphate dimannose (IPM2), we confirmed the direct interaction of DCAR with the polar moiety of AcPIMs by biolayer interferometry and co-crystallization approaches. We also observed a hydrophobic groove extending from the ligand-binding site that is in a suitable position to interact with the lipid portion of whole AcPIMs. These results suggest that the hydroxyl group-binding ability and hydrophobic groove of DCAR mediate its specific binding to pathogen-derived phosphoglycolipids such as mycobacterial AcPIMs. Full Article
pi Deletion of fatty acid transport protein 2 (FATP2) in the mouse liver changes the metabolic landscape by increasing the expression of PPAR{alpha}-regulated genes [Lipids] By www.jbc.org Published On :: 2020-04-24T06:08:45-07:00 Fatty acid transport protein 2 (FATP2) is highly expressed in the liver, small intestine, and kidney, where it functions in both the transport of exogenous long-chain fatty acids and the activation of very-long-chain fatty acids. Here, using a murine model, we investigated the phenotypic impacts of deleting FATP2, followed by a transcriptomic analysis using unbiased RNA-Seq to identify concomitant changes in the liver transcriptome. WT and FATP2-null (Fatp2−/−) mice (5 weeks) were maintained on a standard chow diet for 6 weeks. The Fatp2−/− mice had reduced weight gain, lowered serum triglyceride, and increased serum cholesterol levels and attenuated dietary fatty acid absorption. Transcriptomic analysis of the liver revealed 258 differentially expressed genes in male Fatp2−/− mice and a total of 91 in female Fatp2−/− mice. These genes mapped to the following gene ontology categories: fatty acid degradation, peroxisome biogenesis, fatty acid synthesis, and retinol and arachidonic acid metabolism. Targeted RT-quantitative PCR verified the altered expression of selected genes. Of note, most of the genes with increased expression were known to be regulated by peroxisome proliferator–activated receptor α (PPARα), suggesting that FATP2 activity is linked to a PPARα-specific proximal ligand. Targeted metabolomic experiments in the Fatp2−/− liver revealed increases of total C16:0, C16:1, and C18:1 fatty acids; increases in lipoxin A4 and prostaglandin J2; and a decrease in 20-hydroxyeicosatetraenoic acid. We conclude that the expression of FATP2 in the liver broadly affects the metabolic landscape through PPARα, indicating that FATP2 provides an important role in liver lipid metabolism through its transport or activation activities. Full Article
pi Glycation-mediated inter-protein cross-linking is promoted by chaperone-client complexes of {alpha}-crystallin: Implications for lens aging and presbyopia [Glycobiology and Extracellular Matrices] By www.jbc.org Published On :: 2020-04-24T06:08:45-07:00 Lens proteins become increasingly cross-linked through nondisulfide linkages during aging and cataract formation. One mechanism that has been implicated in this cross-linking is glycation through formation of advanced glycation end products (AGEs). Here, we found an age-associated increase in stiffness in human lenses that was directly correlated with levels of protein–cross-linking AGEs. α-Crystallin in the lens binds to other proteins and prevents their denaturation and aggregation through its chaperone-like activity. Using a FRET-based assay, we examined the stability of the αA-crystallin–γD-crystallin complex for up to 12 days and observed that this complex is stable in PBS and upon incubation with human lens–epithelial cell lysate or lens homogenate. Addition of 2 mm ATP to the lysate or homogenate did not decrease the stability of the complex. We also generated complexes of human αA-crystallin or αB-crystallin with alcohol dehydrogenase or citrate synthase by applying thermal stress. Upon glycation under physiological conditions, the chaperone–client complexes underwent greater extents of cross-linking than did uncomplexed protein mixtures. LC-MS/MS analyses revealed that the levels of cross-linking AGEs were significantly higher in the glycated chaperone–client complexes than in glycated but uncomplexed protein mixtures. Mouse lenses subjected to thermal stress followed by glycation lost resilience more extensively than lenses subjected to thermal stress or glycation alone, and this loss was accompanied by higher protein cross-linking and higher cross-linking AGE levels. These results uncover a protein cross-linking mechanism in the lens and suggest that AGE-mediated cross-linking of α-crystallin–client complexes could contribute to lens aging and presbyopia. Full Article