tom yuan

Realizacja badań podjętych w ramach niniejszej pracy ma służyć celowi nadrzędnemu, jakim jest rozpoznanie potencjału inicjatywy lokalnej w kontekście aktywizacji społeczności lokalnych Łodzi. Główną metodą badawczą było studium przypadku oparte zarówno na analizie danych ilościowych dotyczących realizacji zadań w ramach inicjatyw lokalnych podejmowanych w Łodzi w latach 2013–2019, jak i analizie danych jakościowych (analizie treści) poszczególnych projektów, które zostały w tym czasie zrealizowane. Analiza ta umożliwia po pierwsze określenie skali wykorzystania wymienionego narzędzia w procesie współkształtowania przestrzeni miejskich przez społeczności lokalne, a po drugie, wskazanie podstawowych rodzajów działań podejmowanych przez mieszkańców, co pozwala na identyfikację ich podstawowych potrzeb i problemów, a przede wszystkim propozycji na ich zapewnienie lub rozwiązanie.

Bispecific antibodies have emerged as a promising strategy for curtailing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune escape. This brief report highlights RBT-0813 (also known as TB493-04), a synthetic, humanized, receptor-binding domain (RBD)-targeted bispecific antibody that retains picomolar affinity to the Spike (S) trimers of all major variants of concern and neutralizes both SARS-CoV-2 Delta and Omicron in vitro.

Background Development of successful neutralizing antibodies is dependent upon broad epitope coverage to increase the likelihood of achieving therapeutic function. Recent advances in synthetic biology have allowed us to conduct an epitope binning study on a large panel of antibodies identified to bind to Ebola virus glycoprotein with only published sequences. Methods and Results A rapid, first-pass epitope binning experiment revealed seven distinct epitope families that overlapped with known structural epitopes from the literature. A focused set of antibodies was selected from representative clones per bin to guide a second-pass binning that revealed previously unassigned epitopes, confirmed epitopes known to be associated with neutralizing antibodies, and demonstrated asymmetric blocking of EBOV GP from allosteric effectors reported from literature. Conclusions Critically, this workflow allows us to probe the epitope landscape of EBOV GP without any prior structural knowledge of th...

Proteins, large biological molecules synthesized by living organisms, serve a wide array of functions. Many proteins operate as molecular scaffolds for binding to other proteins; in fact, the vast majority of molecular interactions in biology are made possible by protein-protein interactions. Over the past 15 years, powerful techniques have been developed to generate protein-based ligands in vitro to virtually any protein target. The fundamental steps to any protein engineering effort remain the same. The protein target of interest is modified to create a mutant with preferable biochemical characteristics. The protein is then expressed and purified in large quantities for use in therapeutic or diagnostic applications. In this thesis, I describe a multifaceted approach to address the diversification, identification, and production steps of the protein engineering process.Currently, the vast majority of binding molecules that have been developed for use in biomedical research are eith...

The Wnt signaling pathway is intricately connected with bone mass regulation in humans and rodent models. We designed an antibody-based platform that generates potent and selective Wnt mimetics. Using this platform, we engineer bi-specific Wnt mimetics that target Frizzled and low-density lipoprotein receptor-related proteins and evaluate their effects on bone accrual in murine models. These synthetic Wnt agonists induce rapid and robust bone building effects, and correct bone mass deficiency and bone defects in various disease models, including osteoporosis, aging, and long bone fracture. Furthermore, when these Wnt agonists are combined with antiresorptive bisphosphonates or anti-sclerostin antibody therapies, additional bone accrual/maintenance effects are observed compared to monotherapy, which could benefit individuals with severe and/or acute bone-building deficiencies. Our data support the continued development of Wnt mimetics for the treatment of diseases of low bone mineral...

Community of antibodies against COVID-19 The severe acute respiratory syndrome coronavirus 2 spike protein is the basis of many vaccines and is a primary target of neutralizing antibodies after COVID-19 infection. The Coronavirus Immunotherapeutic Consortium (CoVIC), comprising 56 partners across the world, has analyzed a panel of 269 monoclonal antibodies (mAbs) and, on the basis of competition profiles, sorted 186 mAbs that target the receptor binding domain into seven communities. Hastie et al . went on to structurally analyze representative antibody binding and used pseudovirus neutralization assays to study the effect of spike mutations on antibody function, including the combinations of mutations found in certain variants of concern. These results are important to guide both treatment and prevention efforts. —VV

Metal(H2O2) complexes have been implicated in kinetic and computational studies but have never been observed. Accordingly, H2O2 has been described as a very weak ligand. We report the first metal(H2O2) adduct, which is made possible by incorporating intramolecular hydrogen-bonding interactions with bound H2O2. This Zn(II)(H2O2) complex decays in solution by a second-order process that is slow enough to enable characterization of this species by X-ray crystallography. This report speaks to the intermediacy of metal(H2O2) adducts in chemistry and biology and opens the door to exploration of these species in oxidation catalysis.

Recombinant protein overexpression of large proteins in bacteria often results in insoluble and misfolded proteins directed to inclusion bodies. We report the application of shear stress in micrometer-wide, thin fluid films to refold boiled hen egg white lysozyme, recombinant hen egg white lysozyme, and recombinant caveolin-1. Furthermore, the approach allowed refolding of a much larger protein, cAMP-dependent protein kinase A (PKA). The reported methods require only minutes, which is more than 100 times faster than conventional overnight dialysis. This rapid refolding technique could significantly shorten times, lower costs, and reduce waste streams associated with protein expression for a wide range of industrial and research applications.

To evaluate clinical, microbiologic, and pathologic outcomes in mice after inoculation with 4 equine-origin Corynebacterium pseudotuberculosis strains. 15 C3H/HeJ mice. In a preliminary study, the optimum route of inoculation was determined. In the main study, mice were allocated to 4 treatment groups (3 mice/group). One slow- or rapid-growing equine-origin C pseudotuberculosis strain was inoculated ID into the mice of each treatment group. All 4 strains had distinct tropism for the liver. Histologic lesions associated with rapid-growing strains included focally extensive unencapsulated areas of acute, massive coagulative necrosis of hepatocytes with intralesional colonies of bacteria and variable portal hepatitis characterized by accumulations of mononuclear and polymorphonuclear inflammatory cells. In contrast, the livers of mice inoculated with slow-growing strains had multiple discrete, randomly distributed foci of hepatocellular necrosis and neutrophilic hepatitis that were considerably less severe than the lesions in the mice inoculated with the rapid-growing strains. Significantly more bacterial colonies were recovered from the organs of mice inoculated with rapid-growing than with slow-growing strains of bacteria. Bacteria were isolated from the liver, spleen, lungs, and mesenteric lymph nodes of mice inoculated with rapid-growing strains and from the liver and lymph nodes of mice inoculated with slow-growing strains. Study of host-bacteria interactions in hosts that are naturally infected with C pseudotuberculosis is difficult because of underlying genetic variability among animals, expense, and requirements for multiple replicates and control animals. The C3H/HeJ mice may provide a useful means for studying virulence mechanisms of C pseudotuberculosis.