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The SARS-CoV-2 pandemic alerted the potential for significant harm due to future cross-species transmission of various animal coronaviruses to human. There is a significant need of antibody-based drugs to treat patients infected with previously unseen coronaviruses. In this study, we generated CV804, an antibody that binds to the S2 domain of SARS-CoV-2 spike protein, which is highly conserved across the coronavirus family and less susceptible to mutations. CV804 demonstrated broad cross-reactivities not only disease-associated human beta coronaviruses including SARS-CoV, MERS-CoV, HCoV-OC43, HCoV-HKU1 and with existing mutant strains of SARS-CoV-2 and but also with 20 representative animal-origin coronaviruses. CV804 exhibits strong antibody-dependent cellular cytotoxicity (ADCC) to SARS-CoV-2 spike protein expressed on cells in vitro, while completely lacks virus-neutralization activity. In animal models, CV804 suppressed disease progression caused by SARS-CoV-2 infection. Structural studies using HDX-MS combined with reactivity analysis with point mutants of recombinant spike proteins revealed that CV804 binds to a unique conformational epitope within the S2 domain of the spike proteins that is highly conserved among various coronaviruses. Overall, obtained data suggest that the non-neutralizing CV804 antibody recognizes the conformational structure of the spike protein displayed on the surface of infected cells and weakens the viral virulence by supporting the host immune cells' attack through ADCC activity in vivo. The CV804 epitope information revealed in this study is useful for designing pan-corona antibody therapeutics and universal coronavirus vaccines for preparing potential future pandemics. [ABSTRACT FROM AUTHOR] more...

The importance of treating non‐pulmonary vein (PV) foci is increasing with improvements in the durability of PV isolation. We describe two cases wherein non‐PV foci were induced by mechanical irritation and conventional induction in the same area, which was impossible to induce after ablation, suggesting a relationship between mechanical irritation and induction of non‐PV foci. In a recurrent case of non‐PV foci, atrial fibrillation (AF) was induced only by mechanical irritation. No recurrence has been observed since the ablation of the area. Thus, treatment of the AF induction site with mechanical irritation could be considered an effective therapy for non‐PV foci. [ABSTRACT FROM AUTHOR] more...

Wallemia (Wallemiales, Wallemiomycetes) is a genus of xerophilic Fungi of uncertain phylogenetic position within Basidiomycota. Most commonly found as food contaminants, species of Wallemia have alsobeen isolated from hypersaline environments. The ability to tolerate environments with reduced wateractivity is rare in Basidiomycota. We sequenced the genome of W. sebi in order to understand its adaptations for surviving in osmotically challenging environments, and we performed phylogenomic andultrastructural analyses to address its systematic placement and reproductive biology. W. sebi has a compact genome (9.8 Mb), with few repeats and the largest fraction of genes with functional domains compared with other Basidiomycota. We applied several approaches to searching for osmotic stress-relatedproteins. In silico analyses identied 93 putative osmotic stress proteins; homology searches showedthe HOG (High Osmolarity Glycerol) pathway to be mostly conserved. Despite the seemingly reducedgenome, several gene family expansions and a high number of transporters (549) were found that alsoprovide clues to the ability of W. sebito colonize harsh environments. Phylogenetic analyses of a 71-protein dataset support the position of Wallemia as the earliest diverging lineage of Agaricomycotina, whichis conrmed by septal pore ultrastructure that shows the septal pore apparatus as a variant of the Tremella-type. Mating type gene homologs were idented although we found no evidence of meiosis duringconidiogenesis, suggesting there may be aspects of the life cycle of W. sebi that remain cryptic more...

Engineered living cells have been designed to perform a broad variety of functions (8-16) but, with few exceptions, complex computational constructs (such as comparators, bit adders or multiplexers) are difficult [...], Ongoing efforts within synthetic and systems biology have been directed towards the building of artificial computational devices (1) using engineered biological units as basic building blocks (2,3). Such efforts, inspired in the standard design of electronic circuits (4-7), are limited by the difficulties arising from wiring the basic computational units (logic gates) through the appropriate connections, each one to be implemented by a different molecule. Here, we show that there is a logically different form of implementing complex Boolean logic computations that reduces wiring constraints thanks to a redundant distribution of the desired output among engineered cells. A practical implementation is presented using a library of engineered yeast cells, which can be combined in multiple ways. Each construct defines a logic function and combining cells and their connections allow building more complex synthetic devices. As a proof of principle, we have implemented many logic functions by using just a few engineered cells. Of note, small modifications and combination of those cells allowed for implementing more complex circuits such as a multiplexer or a 1-bit adder with carry, showing the great potential for re-utilization of small parts of the circuit. Our results support the approach of using cellular consortia as an efficient way of engineering complex tasks not easily solvable using single-cell implementations. more...

Research has been conducted on Aspergillus nidulans histidine kinase gene which encodes membrane-type two-component signaling protein. The cloning and characterization of this gene have been carried out, and the results suggest that A. nidulans has complex and robust osmoregulatory systems. more...

We describe an autopsy case of a 75-year-old female with limited cutaneous systemic sclerosis (lcSSc) and gangrene due to macrovascular involvement. She was diagnosed with lcSSc complicated with pulmonary arterial hypertension and digital ulcers 9 years before admission. She had recurrent and refractory lower limb ulcers (LLUs), and died because of sepsis caused by gangrene infection. Autopsy findings revealed severely thickened arterial walls of the visceral organs, consistent with vascular involvement of SSc. Systemic vascular involvement in lcSSc may progress in patients with LLUs who harbour several risk factors for vascular involvement. [ABSTRACT FROM AUTHOR] more...