Hans Wenzl
Trans. Amer. Math. Soc. 373 (2020), 3295-3322.
Abstract, references and article information

M. V. Pratsiovytyi and S. P. Ratushniak
Theor. Probability and Math. Statist. 99 (2020), 211-228.
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.

(The Korea Advanced Institute of Science and Technology (KAIST)) A research team led by Distinguished Professor Sang-Yup Lee reported the production of a microbial strain capable of the massive production of succinic acid with the highest production efficiency to date. This strategy of integrating systems metabolic engineering with enzyme engineering will be useful for the production of industrially competitive bio-based chemicals.

Last month, Prime Minister Andrew Holness announced the establishment of an Economic Recovery Task Force, chaired by Finance Minister Dr Nigel Clarke. The multisectoral task force, which is mandated to oversee Jamaica's economic recovery from...

Plasma lipoprotein (a) [Lp(a)] levels are largely determined by variation in the LPA gene, which codes for apo(a). Genome-wide association studies (GWASs) have identified nonsynonymous variants in LPA that associate with low Lp(a) levels, although their effect on apo(a) function is unknown. We investigated two such variants, R990Q and R1771C, which were present in four null Lp(a) individuals, for structural and functional effects. Sequence alignments showed the R990 and R1771 residues to be highly conserved and homologous to each other and to residues associated with plasminogen deficiency. Structural modeling showed both residues to make several polar contacts with neighboring residues that would be ablated on substitution. Recombinant expression of the WT and R1771C apo(a) in liver and kidney cells showed an abundance of an immature form for both apo(a) proteins. A mature form of apo(a) was only seen with the WT protein. Imaging of the recombinant apo(a) proteins in conjunction with markers of the secretory pathway indicated a poor transit of R1771C into the Golgi. Furthermore, the R1771C mutant displayed a glycosylation pattern consistent with ER, but not Golgi, glycosylation. We conclude that R1771 and the equivalent R990 residue facilitate correct folding of the apo(a) kringle structure and mutations at these positions prevent the proper folding required for full maturation and secretion. To our knowledge, this is the first example of nonsynonymous variants in LPA being causative of a null Lp(a) phenotype.

Using the NCR form of a surrogate pair as an input string to the UNICODE function does not convert the string to the appropriate display character.

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.

WHAT STARTED as an idea of two Barbadians – Ian Webster and Cheyne Jones – transformed into We Got This, a song which proved enough to stir the collective imagination of 25 recording artistes from 14 countries across the region, disseminating the...

THE EDITOR, Madam: THE JAMAICAN economy has been underperforming for the last 40 years, during which economic growth averaged approximately one per cent per annum. One of the main reasons for this poor performance is the non-competitive nature of...

3 March 2020

To the extent that perceptions of a crisis in liberal democracy in Europe can be confirmed, this paper investigates the nature of the problem and its causes, and asks what part, if any, digital technology plays in it.

George D. Harris
Jul 1, 2007; 25:115-118
Case Studies

OBJECTIVE

To assess the contemporaneous prevalence of diabetic peripheral neuropathy (DPN) in people with type 1 diabetes (T1D) in Scotland and study its cross-sectional association with risk factors and other diabetic complications.

Boeing announced Tuesday has presented its first unmanned aircraft to the Royal Australian Air Force.

While much attention has been given to the move by U.S. Citizenship and Immigration Services to raise its application fees—including an 83 percent hike to apply for U.S. citizenship—the policy changes embedded in the proposed rule have been less scrutinized. The changes, including the elimination of most fee waivers for lower-income applicants, would likely reduce the number and shift the profile of those getting a green card or other immigration status.

The ADA is calling for nominations for two seats to represent the Association in the Dental Quality Alliance.

The House of Representatives passed a new coronavirus relief bill April 23 that calls for additional funding for federal loan programs to help businesses nationwide, including dental practices, recover from the economic fallout of the pandemic.

OBJECTIVE

To determine the relationship between ATP7B mutations and diabetes in Wilson disease (WD).

New Zealand drew global attention for its unity and support for the Muslim community targeted during the horrific Christchurch attacks. Yet the country's road to inclusion has been far from straightforward, and amid rising diversity it is grappling with the best way to achieve inclusion for its multiethnic population, including indigenous Māori peoples and migrants. This article outlines the opportunities and challenges to fostering multiculturalism against a backdrop of bicultural policies.

WASHINGTON — Latinos and immigrants are at least twice as likely to lack health insurance coverage as the overall population in three central Kansas City metro counties, a new Migration Policy Institute (MPI) study reveals. In fact, they are four times as likely to be uninsured in Johnson County, Kansas. 

In a time of critical shortages of U.S. health-care workers during the COVID-19 pandemic, retired doctors are being called back to work and medical students are graduating on a fast track. There is another important pool that could be tapped: Immigrants and refugees who have college degrees in health fields but are working in low-skilled jobs or out of work. MPI estimates 263,000 immigrants are experiencing skill underutilization and could be a valuable resource.