Quanlei Fang and Jingbo Xia
Proc. Amer. Math. Soc. 148 (2020), 2497-2507.
Abstract, references and article information

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.

Bacterial biofilms are cellular communities that produce an adherent matrix. Exopolysaccharides are key structural components of this matrix and are required for the assembly and architecture of biofilms produced by a wide variety of microorganisms. The human bacterial pathogens Escherichia coli and Salmonella enterica produce a biofilm matrix composed primarily of the exopolysaccharide phosphoethanolamine (pEtN) cellulose. Once thought to be composed of only underivatized cellulose, the pEtN modification present in these matrices has been implicated in the overall architecture and integrity of the biofilm. However, an understanding of the mechanism underlying pEtN derivatization of the cellulose exopolysaccharide remains elusive. The bacterial cellulose synthase subunit G (BcsG) is a predicted inner membrane–localized metalloenzyme that has been proposed to catalyze the transfer of the pEtN group from membrane phospholipids to cellulose. Here we present evidence that the C-terminal domain of BcsG from E. coli (EcBcsGΔN) functions as a phosphoethanolamine transferase in vitro with substrate preference for cellulosic materials. Structural characterization of EcBcsGΔN revealed that it belongs to the alkaline phosphatase superfamily, contains a Zn2+ ion at its active center, and is structurally similar to characterized enzymes that confer colistin resistance in Gram-negative bacteria. Informed by our structural studies, we present a functional complementation experiment in E. coli AR3110, indicating that the activity of the BcsG C-terminal domain is essential for integrity of the pellicular biofilm. Furthermore, our results established a similar but distinct active-site architecture and catalytic mechanism shared between BcsG and the colistin resistance enzymes.

Pathogenic bacteria of the genera Mycobacterium and Corynebacterium cause severe human diseases such as tuberculosis (Mycobacterium tuberculosis) and diphtheria (Corynebacterium diphtheriae). The cells of these species are surrounded by protective cell walls rich in long-chain mycolic acids. These fatty acids are conjugated to the disaccharide trehalose on the cytoplasmic side of the bacterial cell membrane. They are then transported across the membrane to the periplasm where they act as donors for other reactions. We have previously shown that transient acetylation of the glycolipid trehalose monohydroxycorynomycolate (hTMCM) enables its efficient transport to the periplasm in Corynebacterium glutamicum and that acetylation is mediated by the membrane protein TmaT. Here, we show that a putative methyltransferase, encoded at the same genetic locus as TmaT, is also required for optimal hTMCM transport. Deletion of the C. glutamicum gene NCgl2764 (Rv0224c in M. tuberculosis) abolished acetyltrehalose monocorynomycolate (AcTMCM) synthesis, leading to accumulation of hTMCM in the inner membrane and delaying its conversion to trehalose dihydroxycorynomycolate (h2TDCM). Complementation with NCgl2764 normalized turnover of hTMCM to h2TDCM. In contrast, complementation with NCgl2764 derivatives mutated at residues essential for methyltransferase activity failed to rectify the defect, suggesting that NCgl2764/Rv0224c encodes a methyltransferase, designated here as MtrP. Comprehensive analyses of the individual mtrP and tmaT mutants and of a double mutant revealed strikingly similar changes across several lipid classes compared with WT bacteria. These findings indicate that both MtrP and TmaT have nonredundant roles in regulating AcTMCM synthesis, revealing additional complexity in the regulation of trehalose mycolate transport in the Corynebacterineae.

The Agriculture, Fisheries & Conservation Department (AFCD) and the Leisure & Cultural Services Department (LCSD) announced today that some of their facilities will be closed in light of the latest developments of COVID-19.

Country park barbecue sites and campsites of the AFCD will be closed from 6pm on March 28 for 14 days. There are 163 barbecue sites and 41 campsites under the management of the AFCD.

During the closure of these facilities, barbecue or camping activities in country parks will not be allowed and AFCD staff will step up patrols of the sites concerned and take appropriate action against any violation of relevant regulations.

Call 1823 for enquiries and visit the Enjoy Hiking website for updates on country park facilities.

As for LCSD facilities, its free outdoor leisure facilities will be closed from 6pm on March 28.

Other venues and facilities with services already suspended will continue to be closed until further notice.

All booking applications for the department's recreation and sports facilities, wedding venues, amphitheatres and non-fee charging leisure venues for non-designated use are also suspended.

Meanwhile, the Housing Authority will close its outdoor sports and recreational facilities from 6pm tomorrow until further notice.

The Agriculture, Fisheries & Conservation Department (AFCD) announced today that country park barbecue sites and campsites will remain closed until April 23.

The 163 barbecue sites and 41 campsites managed by AFCD have been closed since March 28. Given the latest development of COVID-19, the department has decided to extend the closure.

During the closure of these facilities, no barbecuing or camping activities are allowed in country parks.

AFCD staff will step up patrols of these sites and violation of relevant regulations will be subject to prosecution.

Call 1823 for enquiries or visit the Enjoy Hiking website for updates.

The department also reminded people visiting country parks to maintain personal and environmental hygiene and maintain social distancing.

The Agriculture, Fisheries & Conservation Department (AFCD) today announced that its barbecue sites and campsites in country parks will be closed until May 7.

It made the decision in light of the latest development of the COVID-19 epidemic and to reduce social contact.

All of these sites have been closed since 6pm on March 28.

During the closure of these facilities, no one should carry out barbecuing or camping activities in country parks.

AFCD staff will step up patrols of the sites and violation of relevant regulations may be subject to prosecution.

In the past two weeks, AFCD took enforcement action against 34 people who carried out barbecuing or camping activities in country parks.

The department will continue to closely monitor the situation and review the arrangement as appropriate.

For the latest updates on facilities in country parks, visit the Enjoy Hiking website.

(ESO) Astronomers have discovered a black hole lying just 1,000 light-years from Earth. The black hole is closer to our solar system than any other found to date and forms part of a triple system that can be seen with the naked eye. The astronomers found evidence for the invisible object by tracking its two companion stars using the MPG/ESO 2.2-meter telescope at ESO's La Silla Observatory in Chile. They say this system could just be the tip of the iceberg.

Pathogenic bacteria of the genera Mycobacterium and Corynebacterium cause severe human diseases such as tuberculosis (Mycobacterium tuberculosis) and diphtheria (Corynebacterium diphtheriae). The cells of these species are surrounded by protective cell walls rich in long-chain mycolic acids. These fatty acids are conjugated to the disaccharide trehalose on the cytoplasmic side of the bacterial cell membrane. They are then transported across the membrane to the periplasm where they act as donors for other reactions. We have previously shown that transient acetylation of the glycolipid trehalose monohydroxycorynomycolate (hTMCM) enables its efficient transport to the periplasm in Corynebacterium glutamicum and that acetylation is mediated by the membrane protein TmaT. Here, we show that a putative methyltransferase, encoded at the same genetic locus as TmaT, is also required for optimal hTMCM transport. Deletion of the C. glutamicum gene NCgl2764 (Rv0224c in M. tuberculosis) abolished acetyltrehalose monocorynomycolate (AcTMCM) synthesis, leading to accumulation of hTMCM in the inner membrane and delaying its conversion to trehalose dihydroxycorynomycolate (h2TDCM). Complementation with NCgl2764 normalized turnover of hTMCM to h2TDCM. In contrast, complementation with NCgl2764 derivatives mutated at residues essential for methyltransferase activity failed to rectify the defect, suggesting that NCgl2764/Rv0224c encodes a methyltransferase, designated here as MtrP. Comprehensive analyses of the individual mtrP and tmaT mutants and of a double mutant revealed strikingly similar changes across several lipid classes compared with WT bacteria. These findings indicate that both MtrP and TmaT have nonredundant roles in regulating AcTMCM synthesis, revealing additional complexity in the regulation of trehalose mycolate transport in the Corynebacterineae.

Invitation Only Research Event

Event participants

Yang Cheng, Professor of International Relations, Assistant Dean, School of International Relations and Public Affairs, Shanghai International Studies University
Yu Jie, Senior Research Fellow, Asia-Pacific Programme, Chatham House
Marcin Kaczmarski, Lecturer in Security Studies, University of Glasgow
Natasha Kuhrt, Lecturer, Department of War Studies, King’s College London
Bobo Lo, Non-Resident Fellow, Lowy Institute
Alexey Maslov, Professor, School of Asian Studies, National Research University, Higher School of Economics, Moscow

Pathogenic bacteria of the genera Mycobacterium and Corynebacterium cause severe human diseases such as tuberculosis (Mycobacterium tuberculosis) and diphtheria (Corynebacterium diphtheriae). The cells of these species are surrounded by protective cell walls rich in long-chain mycolic acids. These fatty acids are conjugated to the disaccharide trehalose on the cytoplasmic side of the bacterial cell membrane. They are then transported across the membrane to the periplasm where they act as donors for other reactions. We have previously shown that transient acetylation of the glycolipid trehalose monohydroxycorynomycolate (hTMCM) enables its efficient transport to the periplasm in Corynebacterium glutamicum and that acetylation is mediated by the membrane protein TmaT. Here, we show that a putative methyltransferase, encoded at the same genetic locus as TmaT, is also required for optimal hTMCM transport. Deletion of the C. glutamicum gene NCgl2764 (Rv0224c in M. tuberculosis) abolished acetyltrehalose monocorynomycolate (AcTMCM) synthesis, leading to accumulation of hTMCM in the inner membrane and delaying its conversion to trehalose dihydroxycorynomycolate (h2TDCM). Complementation with NCgl2764 normalized turnover of hTMCM to h2TDCM. In contrast, complementation with NCgl2764 derivatives mutated at residues essential for methyltransferase activity failed to rectify the defect, suggesting that NCgl2764/Rv0224c encodes a methyltransferase, designated here as MtrP. Comprehensive analyses of the individual mtrP and tmaT mutants and of a double mutant revealed strikingly similar changes across several lipid classes compared with WT bacteria. These findings indicate that both MtrP and TmaT have nonredundant roles in regulating AcTMCM synthesis, revealing additional complexity in the regulation of trehalose mycolate transport in the Corynebacterineae.

Chronic low-grade inflammation plays a central role in the pathophysiology of gestational diabetes mellitus (GDM). In order to investigate the ability of different inflammatory blood cell parameters in predicting the development of GDM and pregnancy outcomes, 258 women with GDM and 1154 women without were included in this retrospective study. First-trimester neutrophil count outperformed white blood cell (WBC) count, and neutrophil-to-lymphocyte ratio (NLR) in the predictability for GDM. Subjects were grouped based on tertiles of neutrophil count during their first-trimester pregnancy. The results showed that as the neutrophil count increased, there was a step-wise increase in GDM incidence, as well as glucose and glycosylated hemoglobin (HbA1c) level, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), macrosomia incidence and newborn weight. Neutrophil count was positively associated with pre-pregnancy Body Mass Index (BMI), HOMA-IR and newborn weight. Additionally, neutrophil count was an independent risk factor for the development of GDM, regardless of the history of GDM. Spline regression showed that there was a significant linear association between GDM incidence and continuous neutrophil count when it exceeded 5.0 x 10⁹/L. This work suggested that first-trimester neutrophil count is closely associated with the development of GDM and adverse pregnancy outcomes.

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.

2 May 2019 , Volume 95, Number 3

Invitation Only Research Event

Event participants

Yang Cheng, Professor of International Relations, Assistant Dean, School of International Relations and Public Affairs, Shanghai International Studies University
Yu Jie, Senior Research Fellow, Asia-Pacific Programme, Chatham House
Marcin Kaczmarski, Lecturer in Security Studies, University of Glasgow
Natasha Kuhrt, Lecturer, Department of War Studies, King’s College London
Bobo Lo, Non-Resident Fellow, Lowy Institute
Alexey Maslov, Professor, School of Asian Studies, National Research University, Higher School of Economics, Moscow

Quantum physics dictates that Looked at directly matter will disappear. Big physics says that electrons can be bound, Entangled, still Unified theory does not allow multiple existences. These are matters of the heart; Sometimes looking at love directly can destroy it, And we don’t want lovers disappearing, To burnt, brawny, Ulaanbaatar without us, we Want […]

IT IS said that every cloud has a silver lining, and that could still hold true, even in the midst of a terrifying global pandemic. Despite COVID-19, the cycle of life continues, and out of it has sprung forth an inspiring poetry competition,...

Sandra Ferguson resides with her children and grandchildren in a concrete dwelling that is sectioned into four living quarters in the Fort George Road area of Annotto Bay. With 10 of them sharing kitchen and bathroom facilities, Ferguson said...

With Greg Holland now signed, will he be the closer or is that still going to be Archie Bradley? Beat reporter Steve Gilbert answers this question and more from fans as Spring Training approaches.

After watching his pitchers and catchers go through their first workout Wednesday, D-backs manager Torey Lovullo said it was too early to say whether Archie Bradley, Greg Holland or Yoshihisa Hirano would be his closer come Opening Day.

It was the eighth inning of a late September game against the Dodgers when D-backs right-hander Yoan Lopez showed that not only might he have the stuff to be a future closer, but also the moxie of one as well.

Lalantha Leelarathna
Jul 1, 2014; 37:1931-1937
Emerging Technologies and Therapeutics

Boris P. Kovatchev
Jul 1, 2013; 36:1851-1858
Diabetes Care Symposium

Roman Hovorka
May 1, 2014; 37:1204-1211
Advances in Artificial Pancreas Development

I am torn, I know it is time to upgrade my phone, but I don't know whether to upgrade to just accept the larger phone size and go with the 2nd gen SE or go with an android. I'd be interested to know what the closest equivalent android device there is to the 1st gen SE. I am open to a bigger screen size, but not a bigger phone. So, if there was an andriod that was all screen on the front, but was similar size to the original SE, I would be open to that.

The failure of Geert Wilders’ right-wing, anti-Islam Freedom Party (PVV) to become the top vote-getter in the Dutch parliamentary elections is being hailed as proof of the limits of anti-Muslim rhetoric and even the “waning” of the appeal of right-wing populism. But as this commentary explores, a closer reading leads one to a more nuanced interpretation of the results and the recognition that Wilders will remain a major force.

WASHINGTON – Even as governments in Latin America and the Caribbean have taken generous and innovative steps to address forced displacement from Venezuela and more recently Nicaragua, the warm welcome has cooled in places amid the vast scale of the inflows, strains on public services and growing public concern.

School buildings in Massachusetts will remain closed through the end of the academic year, but remote learning will continue, Gov. Charlie Baker announced Tuesday.

A measure now before Virginia's governor would let teachers bargain with local boards over wages and working conditions if a local board authorizes it.

"We have a responsibility to save lives," Ohio Gov. Mike DeWine said on Twitter. "We could have waited to close schools, but based on advice from health experts, this is the time to do it."

New York’s schools and colleges will remain shut through the end of the academic year because of the coronavirus pandemic, Gov. Andrew Cuomo said Friday.

At least four Kentucky school districts were forced to close last Thursday as hundreds of teachers called in sick to continue protesting what they believe to be anti-public education proposals in the state legislature.

Gov. Andrew Cuomo pushed back on the Mayor Bill de Blasio's announcement, however, saying "no decision" had been made about reopening schools in New York City or elsewhere in the state.

New York’s schools and colleges will remain shut through the end of the academic year because of the coronavirus pandemic, Gov. Andrew Cuomo said Friday.

New York’s schools and colleges will remain shut through the end of the academic year because of the coronavirus pandemic, Gov. Andrew Cuomo said Friday.