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Topic Review
Study HuNoV in Gnotobiotic Pigs
Human noroviruses (HuNoVs) are the leading causative agents of epidemic and sporadic acute gastroenteritis that affect people of all ages worldwide. They are responsible for over 20% of all the AGE cases annually. Among susceptible individuals, it has been shown that very low inoculum doses are sufficient to generate a full course of infection with high titers of virus shed in feces. Very few dose–response studies have been carried out to determine the median infectious dose of HuNoVs. Here, we evaluated the median infectious dose (ID50) and diarrhea dose (DD50) of the GII.4/2003 variant of HuNoV (Cin-2) in the gnotobiotic pig model of HuNoV infection and disease. Using different mathematical approaches (classical, and contemporary methods), we estimated the ID50 and DD50 to be between 2400–3400 RNA copies, and 21,000–38,000 RNA copies, respectively. Contemporary dose–response models offer greater flexibility and accuracy in estimating ID50. In contrast to classical methods of endpoint estimation, dose–response modelling allows seamless analyses of data that may include inconsistent dilution factors between doses or numbers of subjects per dose group, or small numbers of subjects. Although this investigation is consistent with state-of-the-art ID50 determinations and offers an advancement in clinical data analysis, it is important to underscore that such analyses remain confounded by pathogen aggregation. Regardless, challenging virus strain ID50 determination is crucial for identifying the true infectiousness of HuNoVs and for the accurate evaluation of protective efficacies in pre-clinical studies of therapeutics, vaccines and other prophylactics using this reliable animal model.
  • 643
  • 10 Sep 2020
Topic Review
Structure, Sequence and Immunopathology of SARS-CoV-2
Since November 2019, SARS-CoV-2 has been a matter of global concern due to its rapid spread, the millions of deaths it caused, and repeated waves of infections. One after another, many variants of this novel virus have come into existence due to its constant mutability, specifically in the spike glycoprotein region. The tally for variants of concern (VOCs), which already include Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2), has increased to five with the latest appearance of Omicron (B.1.1.529).
  • 656
  • 10 Jun 2022
Topic Review
Structure, Expression Regulation, and Subcellular Localization of USP16
Ubiquitin-specific peptidase 16 (USP16) is a deubiquitinase that plays a role in the regulation of gene expression, cell cycle progression, and various other functions. It was originally identified as the major deubiquitinase for histone H2A and has since been found to deubiquitinate a range of other substrates, including proteins from both the cytoplasm and nucleus. USP16 is phosphorylated when cells enter mitosis and dephosphorylated during the metaphase/anaphase transition. While much of USP16 is localized in the cytoplasm, separating the enzyme from its substrates is considered an important regulatory mechanism. Some of the functions that USP16 has been linked to include DNA damage repair, immune disease, tumorigenesis, protein synthesis, coronary artery health, and male infertility. The strong connection to immune response and the fact that multiple oncogene products are substrates of USP16 suggests that USP16 may be a potential therapeutic target for the treatment of certain human diseases.
  • 897
  • 06 Apr 2023
Topic Review
Structure-Dynamic Determinants of Regulatory Divergence in Eukaryotic NCXs
The plasma-membrane Na+/Ca2+ exchangers (NCXs) mediate Ca2+ extrusion/entry to dynamically shape Ca2+ signaling in biological systems ranging from bacteria to humans. The NCX gene orthologs, isoforms, and their splice variants are expressed in a tissue-specific manner and exhibit nearly 104-fold differences in the transport rates and diverse regulatory specificities to match the cell-specific requirements. About 280 residues are directly involved in the folding of Ca2+ binding CBD1 and CBD2 domains that form a two-domain regulatory tandem (CBD12). The X-ray and NMR structures of the CBD1, CBD2, and CBD12 domains reveal a β-immunoglobulin (Ig)-like folding, where two antiparallel β-sheets (with A-B-E and D-C-F-G strands) form a seven-strand β-sandwich motif. The remarkable similarity between the folding structures of CBD1 and CBD2 is evident since the overlay of the CBD1 and CBD2 crystal structures display nearly identical folding with RMSD = 1.3 Å, although all the Ca2+ binding sites in both CBDs reside at the C-terminal ends of distal loops. However, the striking difference between the CBDs is that the CBD1 domain contains four Ca2+ binding sites in all known variants, whereas in the CBD2 domain, the splicing segment varies the number of Ca2+ binding sites from zero to three. The challenge is to resolve the underlying structure-dynamic mechanisms that can explain how the Ca2+ interactions with different variants of eukaryotic NCXs can result in positive, negative, and neutral responses. 
  • 327
  • 09 Jan 2023
Topic Review
Structure-Based Approach in Drug Design
Structure-based drug design (SBDD) is the computational approach that relies on knowledge of 3D structures of the biological targets to identify or design the potential chemical structure suitable for clinical tests. With the explosion of genomic, functional, and structural information in recent decades, the majority of biological targets with 3D structure have been identified and stimulated the applications of structure-based approaches in the current design pipeline. SBDD is popular for virtual screening to filter the drug-like compounds from a large library of small molecules, including widely applied approaches, such as docking and structure-based pharmacophore design. 
  • 4.1K
  • 24 Jan 2022
Topic Review
Structure of the North American Beef Industry
North America is a large producer of beef and contains approximately 12% of the world’s cattle inventory. Feedlots are an integral part of modern cattle production in North America, producing a high-quality, wholesome protein food for humans. 
  • 994
  • 09 Mar 2023
Topic Review
Structure of the MRN Complex
The MRE11, RAD50, and NBN genes encode for the nuclear MRN protein complex, which senses the DNA double strand breaks and initiates the DNA repair. The MRN complex also participates in the activation of ATM kinase, which coordinates DNA repair with the p53-dependent cell cycle checkpoint arrest. Carriers of homozygous germline pathogenic variants in the MRN complex genes or compound heterozygotes develop phenotypically distinct rare autosomal recessive syndromes characterized by chromosomal instability and neurological symptoms. 
  • 689
  • 06 Apr 2023
Topic Review
Structure of Rubisco，Dinoflagellates
Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), is one of the best studied enzymes. Rubisco catalyses CO2 assimilation and therefore tt is crucial for photosynthesis, and for all of biosphere’s productivity. There are four isoforms of this enzyme, differing by amino acid sequence composition and quaternary structure. However, there is still a group of organisms, dinoflagellates, single-cell eukaryotes, that are confirmed to possess Rubisco, but no successful purification of the enzyme of such origin, and hence a generation of a crystal structure was reported to date.
  • 773
  • 16 Aug 2021
Topic Review
Structure of Glycosylated Arsenicals
Microalgae are abundant components of the biosphere rich in low molecular weight carbohydrate-containing natural products (glycoconjugates). Glycoconjugates take part in the processes of photosynthesis, provide producers with important biological molecules, influence other organisms and are known by their biological activities. Some of them, for example, glycosylated toxins and arsenicals, are detrimental and can be transferred via food chains into higher organisms, including humans. 
  • 281
  • 05 Sep 2023
Topic Review
Structure of G Domain among G Proteins
The ancient guanine nucleotide-binding (G) proteins are a group of critical regulatory and signal transduction proteins, widely involved in diverse cellular processes of all kingdoms of life. YchF is a kind of universally conserved novel unconventional G protein that appears to be crucial for growth and stress response in eukaryotes and bacteria. YchF is able to bind and hydrolyze both adenine nucleoside triphosphate (ATP) and guanosine nucleoside triphosphate (GTP), unlike other members of the P-loop GTPases.
  • 483
  • 04 May 2023
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