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Single-chain Fv (scFv) is a recombinant small antibody in which a polypeptide linker connects the variable regions of the light chain (VL) and the heavy chain (VH). The practical use of scFv, however, has been prevented by its tendency to aggregate due to interchain VL–VH interactions. We recently developed a cyclic scFv whose N-terminus and C-terminus were connected by protein ligation techniques. Biophysical comparisons between cyclic and linear scFv have been conducted, but cell biological evaluations remain unexplored. Here we studied the properties of cyclic and linear scFv derived from nivolumab. Biophysical studies revealed that the thermal stability was not changed but that the antigen-binding activity was approximately 3-fold higher as a result of circularization. A cell-based PD-1/PD-L1 interaction inhibitory assay revealed that the biological activity of scFv was markedly higher in the circularized form. In addition, biophysical analysis of scFv proteins incubated in the presence of serum revealed that circularization suppressed the decrease in antigen-binding activity. It could be assumed that circularization of scFv improved stability in the presence of serum, which in turn would suggest the applicability of cyclic scFv as a biopharmaceutical format. [ABSTRACT FROM AUTHOR]

Catheter-related bloodstream infections (CRBSIs) caused by Lactobacillus spp. and Lacticaseibacillus spp. are rare, and their clinical course and optimal treatment remain uncertain. In this report, we present a 46-year-old male patient who experienced clinically diagnosed Lacticaseibacillus paracasei CRBSI on four separate occasions, despite receiving systemic administration of antibiotics and antimicrobial lock therapy. The patient did not develop L. paracasei bacteremia after catheter removal. This case report furthers our knowledge of CRBSI caused by Lactobacillus and related genera and highlights the need for further research. [ABSTRACT FROM AUTHOR]

Induction of antibodies (Abs) against the conformational CD4‐induced (CD4i) epitope is frequent in HIV‐1 infection. However, the mechanism of development of anti‐CD4i Abs is unclear. We used anti‐idiotypic (aID) monoclonal Abs (mAbs) of anti‐CD4i mAbs to isolate anti‐CD4i mAbs from infected subjects and track the causative antigens. One anti‐aID mAb sorted from infected subjects by aID mAbs had the characteristics of anti‐CD4i Abs, including IGHV1‐69 usage and ability to bind to HIV‐1 Env enhanced by sCD4. Critical amino acid sequences for the binding of six anti‐aID mAbs, with shared idiotope to anti‐CD4i mAbs, were analysed by phage display. The identified amino acid sequences showed similarity to proteins from human microbiota and infectious agents. Peptides synthesized from Caudoviricetes sp and Vibrio vulnificus based on the identified sequences were reactive to most anti‐aID and some anti‐CD4i mAbs. These results suggest that anti‐CD4i Abs may evolve from B cells primed by microorganisms. [ABSTRACT FROM AUTHOR]

To clarify the composition of food ingested by blue mussels (Mytilus edulis) in the Menai Strait, where the largest mussel bed in the United Kingdom lies, hydrodynamic observations with organic carbon and nitrogen biochemical analysis were conducted. This strait is characterized by a narrow channel and wide tidal flats with large tidal mixing that influences the distribution of particulate organic matter (POM), which is food for mussels. The maximum velocities of the tidal currents were estimated to be 0.5-1.0 m [s.sup.-1] during northeastward flow and 0.6-1.3 m [s.sup.-1] during southwestward flow. The residual current was southwestward and the water flux was estimated to be 510 [m.sup.3] [s.sup.-1], Field observations indicate that the inflow of pelagic phytoplankton into the strait mainly occurred in the northern region of the strait. Resuspcndcd benthic primary production, however, also causes higher chlorophyll-a concentration in the central region of the strait near the mussel bed and its contribution to mussel growth was estimated to be 22%-50%. The concentrations of chlorophyll-a and particulate organic carbon indicated that the POM in the strait mainly originated from detritus. Benthic microalgae is. however, an important factor to understand the total primary production in the strait. The consumption of the primary producers was estimated to be approximately 6.3 t C [day.sup.-1]. In the phytoplankton community, pelagic and thycopelagic (living in both pelagic and benthic environments) species comprised 59.3%-77.2% and 12.8%-40.7% of the cells, respectively. The primary production by resuspended benthic species in the Liverpool Bay region was considerably larger than that in the Menai Strait region. As a conclusion, the Menai Strait is an area with complex hydrodynamic conditions causing horizontal advection and resuspension of both pelagic and benthic phytoplankton, and this complex would cause the most suitable condition for mussel production. KEY WORDS: mussel, food supply, food consumption, particulate organic matter, phytoplankton, benthic microalgae, stable isotopes. Mytilus edulis, INTRODUCTION The blue mussel Mytilus edulis is one of the most important aquaculture species in the North Atlantic coastal regions. Approximately two-thirds of the total mussel production in the United [...]

Mycoplasma hominis is a bacterium that colonizes the genital tract of some females and males, as well as their respiratory tracts. Although only two cases of deep neck infection have been reported, the associations between the onset and sexual intercourse have not been reported. A healthy 19-year-old female was diagnosed with a left peritonsillar abscess. The patient had sexual intercourse with a new partner, including oral sex, two days prior to symptom onset. It was not known whether the male partner had urethritis symptoms. M. hominis and Fusobacterium necrophorum were isolated from the abscess culture. The patient's condition improved after drainage, and sulbactam ampicillin was switched to oral clindamycin. [ABSTRACT FROM AUTHOR]

Transthyretin (TTR) is a homo-tetrameric serum protein associated with sporadic and hereditary systemic amyloidosis. TTR amyloid formation proceeds by the dissociation of the TTR tetramer and the subsequent partial unfolding of the TTR monomer into an aggregation-prone conformation. Although TTR kinetic stabilizers suppress tetramer dissociation, a strategy for stabilizing monomers has not yet been developed. Here, we show that an N-terminal C10S mutation increases the thermodynamic stability of the TTR monomer by forming new hydrogen bond networks through the side chain hydroxyl group of Ser10. Nuclear magnetic resonance spectrometry and molecular dynamics simulation revealed that the Ser10 hydroxyl group forms hydrogen bonds with the main chain amide group of either Gly57 or Thr59 on the DE loop. These hydrogen bonds prevent the dissociation of edge strands in the DAGH and CBEF β-sheets during the unfolding of the TTR monomer by stabilizing the interaction between β-strands A and D and the quasi-helical structure in the DE loop. We propose that introducing hydrogen bonds to connect the N-terminal region to the DE loop reduces the amyloidogenic potential of TTR by stabilizing the monomer. [ABSTRACT FROM AUTHOR]