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

The Security Bureau today said that the last Hong Kong resident who had contracted COVID-19 while aboard the Diamond Princess cruise ship and was hospitalised in Japan has returned to Hong Kong.

Immigration Department staff that assisted Hong Kong residents in Japan have completed their mission and returned to Hong Kong as well.

In early February, a cluster of COVID-19 infection cases occurred on the Diamond Princess cruise docked in Yokohama.

Of some 3,700 passengers and crew, about 370 were from Hong Kong. The 712 confirmed COVID-19 cases associated with the cruise included 76 Hong Kong residents who were hospitalised in Japan for isolation and treatment.

While three Hong Kong residents passed away, the remaining 73 patients returned to Hong Kong or their places of residence after being discharged from the hospital.

As for other Hong Kong residents on the cruise, the bureau noted that the Hong Kong Special Administrative Region Government arranged three flights, between February 19 and 23, to escort 193 of them back to the city.

Upon arrival, they were transferred to the quarantine centre at Chun Yeung Estate to undergo 14 days of quarantine.

Another 144 Hong Kong residents returned on their own via other flights, including 25 close contacts of the patients who had completed quarantine in Japan.

For those who returned to Hong Kong on their own and did not complete 14 days of quarantine in Japan, they were required to complete the remaining quarantine period at a quarantine centre.

Of the 231 cruise passengers admitted to the quarantine centre at Chun Yeung Estate, nine tested positive for COVID-19 and were sent to hospitals for isolation and treatment.

The Hong Kong SAR Government expressed profound condolences on the passing of the Hong Kong patients and its deepest sympathies to their families.

The SAR Government emphasised that the incident could not have been resolved smoothly without the staunch support of the Office of the Commissioner of the Ministry of Foreign Affairs of the People's Republic of China in the Hong Kong Special Administrative Region, the Embassy of the People’s Republic of China in Japan and Japanese authorities.

The SAR Government also thanked Cathay Pacific Airways and the Airport Authority for their assistance, the bureau added.

The Dr Sun Yat-sen Museum will hold a fun day on November 10 to commemorate Dr Sun's revolutionary journey and enhance public knowledge of the museum.

A variety of activities including a concert, birthday cake motif cardholder workshop and cosplay will be provided.

There will also be virtual reality games and a display of early textbooks for visitors to learn more about Dr Sun's school life in Hong Kong.

In addition, a cultural tour will be held on the Dr Sun Yat-sen Historical Trail. Prior registration is required.

Visitors can also tour the museum's permanent exhibits which comprise precious historical artefacts and a wide range of audiovisual programmes.

Admission is free.

Click here for details.

Joseph B. Nelson
Aug 1, 2017; 30:171-174
From Research to Practice

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.

T-type (Cav3) Ca2+ channels are important regulators of excitability and rhythmic activity of excitable cells. Among other voltage-gated Ca2+ channels, Cav3 channels are uniquely sensitive to oxidation and zinc. Using recombinant protein expression in HEK293 cells, patch clamp electrophysiology, site-directed mutagenesis, and homology modeling, we report here that modulation of Cav3.2 by redox agents and zinc is mediated by a unique extracellular module containing a high-affinity metal-binding site formed by the extracellular IS1–IS2 and IS3–IS4 loops of domain I and a cluster of extracellular cysteines in the IS1–IS2 loop. Patch clamp recording of recombinant Cav3.2 currents revealed that two cysteine-modifying agents, sodium (2-sulfonatoethyl) methanethiosulfonate (MTSES) and N-ethylmaleimide, as well as a reactive oxygen species–producing neuropeptide, substance P (SP), inhibit Cav3.2 current to similar degrees and that this inhibition is reversed by a reducing agent and a zinc chelator. Pre-application of MTSES prevented further SP-mediated current inhibition. Substitution of the zinc-binding residue His191 in Cav3.2 reduced the channel's sensitivity to MTSES, and introduction of the corresponding histidine into Cav3.1 sensitized it to MTSES. Removal of extracellular cysteines from the IS1–IS2 loop of Cav3.2 reduced its sensitivity to MTSES and SP. We hypothesize that oxidative modification of IS1–IS2 loop cysteines induces allosteric changes in the zinc-binding site of Cav3.2 so that it becomes sensitive to ambient zinc.

The cellular energy sensor AMP-activated protein kinase (AMPK) is a metabolic regulator that mediates adaptation to nutritional variations to maintain a proper energy balance in cells. We show here that suckling-weaning and fasting-refeeding transitions in rodents are associated with changes in AMPK activation and the cellular energy state in the liver. These nutritional transitions were characterized by a metabolic switch from lipid to glucose utilization, orchestrated by modifications in glucose levels and the glucagon/insulin ratio in the bloodstream. We therefore investigated the respective roles of glucose and pancreatic hormones on AMPK activation in mouse primary hepatocytes. We found that glucose starvation transiently activates AMPK, whereas changes in glucagon and insulin levels had no impact on AMPK. Challenge of hepatocytes with metformin-induced metabolic stress strengthened both AMPK activation and cellular energy depletion under limited-glucose conditions, whereas neither glucagon nor insulin altered AMPK activation. Although both insulin and glucagon induced AMPKα phosphorylation at its Ser485/491 residue, they did not affect its activity. Finally, the decrease in cellular ATP levels in response to an energy stress was additionally exacerbated under fasting conditions and by AMPK deficiency in hepatocytes, revealing metabolic inflexibility and emphasizing the importance of AMPK for maintaining hepatic energy charge. Our results suggest that nutritional changes (i.e. glucose availability), rather than the related hormonal changes (i.e. the glucagon/insulin ratio), sensitize AMPK activation to the energetic stress induced by the dietary transition during fasting. This effect is critical for preserving the cellular energy state in the liver.

(American Association for Cancer Research) Combining intratumoral electroporation of interleukin-12 (IL-12) DNA (tavokinogene telseplasmid, or TAVO) with the immune checkpoint inhibitor pembrolizumab (Keytruda) led to clinical responses in patients with immunologically quiescent advanced melanoma, according to results from a phase II trial.

(King Abdullah University of Science & Technology (KAUST)) Optical fibers wrapped around date palm trunks could help detect this tree's most destructive pest early enough to save it.

The budget carrier will begin conducting temperature checks via touchless thermometers on June 1. Passengers have to start wearing masks Friday.

(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.

Jan Pearson
Apr 1, 2001; 14:
Articles

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...

18 February 2019

Sperm head shaping is a key event in spermiogenesis and is tightly controlled via the acrosome–manchette network. Linker of nucleoskeleton and cytoskeleton (LINC) complexes consist of Sad1 and UNC84 domain–containing (SUN) and Klarsicht/ANC-1/Syne-1 homology (KASH) domain proteins and form conserved nuclear envelope bridges implicated in transducing mechanical forces from the manchette to sculpt sperm nuclei into a hook-like shape. However, the role of LINC complexes in sperm head shaping is still poorly understood. Here we assessed the role of SUN3, a testis-specific LINC component harboring a conserved SUN domain, in spermiogenesis. We show that CRISPR/Cas9-generated Sun3 knockout male mice are infertile, displaying drastically reduced sperm counts and a globozoospermia-like phenotype, including a missing, mislocalized, or fragmented acrosome, as well as multiple defects in sperm flagella. Further examination revealed that the sperm head abnormalities are apparent at step 9 and that the sperm nuclei fail to elongate because of the absence of manchette microtubules and perinuclear rings. These observations indicate that Sun3 deletion likely impairs the ability of the LINC complex to transduce the cytoskeletal force to the nuclear envelope, required for sperm head elongation. We also found that SUN3 interacts with SUN4 in mouse testes and that the level of SUN4 proteins is drastically reduced in Sun3-null mice. Altogether, our results indicate that SUN3 is essential for sperm head shaping and male fertility, providing molecular clues regarding the underlying pathology of the globozoospermia-like phenotype.

Bokai Song
Apr 28, 2020; 0:RA120.001981v1-mcp.RA120.001981
Research