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1. chinaXiv:202002.00082 [pdf]

ACE2 shedding and furin abundance in target organs may influence the efficiency of SARS-CoV-2 entry

Yuanchen Ma; Yinong Huang; Tao Wang; Andy Peng Xiang; Weijun Huang
Subjects: Medicine, Pharmacy >> Preclinical Medicine

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified lineage B coronavirus, causing rapid worldwide outbreak of Corona Virus Disease 2019 (COVID-19). Despite genetically closed to SARS-CoV, SARS-CoV-2 seems to possess enhanced infectivity and subtle different clinical features, which may hamper the early screening of suspected patients as well as the control of virus transmission. Unfortunately, there are few tools to predict the potential target organ damage and possible clinical manifestations caused by such novel coronavirus. To solve this problem, we investigate the potential host cell entry mechanisms of SARS-CoV-2 through bioinformatics. Using the online single-cell sequence datasets, we analyze the expression of major receptor in host cells that mediates the virus entry, including angiotensin converting enzyme 2 (ACE2), and its co-expressed membrane endopeptidases. The results indicated the differential expression of ADAM10 and ADAM17 might contribute to the ACE2 shedding and affect the membrane ACE2 abundance. We further confirm a putative furin-cleavage site reported recently in the spike protein of SARS-CoV-2, which may facilitate the virus-cell fusion. Based on these findings, we develop a novel approach that comprehensively analyzed the virus receptor expression, ACE2 shedding, membrane fusion activity, virus uptake and virus replication to evaluate the infectivity of SARS-CoV-2 to different human organs. Our results indicate that, in addition to airway epithelia, cardiac tissue and enteric canals are susceptible to SARS-CoV-2 as well.

submitted time 2020-02-27 Hits41658Downloads4294 Comment 0

2. chinaXiv:201705.00711 [pdf]

Esrrb Activates Oct4 Transcription and Sustains Self-renewal and Pluripotency in Embryonic Stem Cells

Xiaofei Zhang(1); Juan Zhang(2); Tao Wang(3); Miguel A. Esteban(3); Duanqing Pei(4)
Subjects: Biology >> Biomedical Laboratory Science

The genetic program of embryonic stem (ES) cells is orchestrated by a core of transcription factors that has OCT4, SOX2, and NANOG as master regulators. Protein levels of these core factors are tightly controlled by autoregulatory and feed-forward transcriptional mechanisms in order to prevent early differentiation. Recent studies have shown that knockdown of Esrrb (estrogen-related-receptor beta), a member of the nuclear orphan receptor family, induces differentiation of mouse ES cells cultured in the presence of leukemia inhibitory factor. It was however not known how knocking down Esrrb exerts this effect. Herein we have identified two ESRRB binding sites in the proximal 5'-untranslated region of the mouse Oct4 gene, one of which is in close proximity to a NANOG binding site. Both ESRRB and NANOG are necessary for maintaining the activity of this promoter in ES cell lines. We have also demonstrated that the two transcription factors interact through their DNA binding domains. This interaction reciprocally modulates their transcriptional activities and may be important to fine-tune ES cell pluripotency. Supporting all of these data, stable transfection of Esrrb in ES cell lines proved sufficient to sustain their characteristics in the absence of leukemia-inhibitory factor. In summary, our experiments help to understand how Esrrb coordinates with Nanog and Oct4 to activate the internal machinery of ES cells.

submitted time 2017-05-10 Hits850Downloads465 Comment 0

3. chinaXiv:201609.00987 [pdf]

The $ Zb\overlineb $ couplings at future e$^+$ e$^?$ colliders

Stefania Gori; Jiayin Gu; Lian-Tao Wang(c; d)
Subjects: Physics >> Nuclear Physics

Many new physics models predict sizable modifications to the SM Zbb couplings, while the corresponding measurements at LEP and SLC exhibit some discrepancy with the SM predictions. After updating the current results on the Zbb coupling constraints from global fits, we list the observables that are most important for improving the Zbb coupling constraints and estimate the expected precision reach of three proposed future e+e- colliders, CEPC, ILC and FCC-ee. We consider both the case that the results are SM-like and the one that the Zbb couplings deviate significantly from the SM predictions. We show that, if we assume the value of the Zbb couplings to be within 68% CL of the current measurements, any one of the three colliders will be able to rule out the SM with more than 99.9999% CL (5 sigma). We study the implications of the improved Zbb coupling constraints on new physics models, and point out their complementarity with the constraints from the direct search of new physics particles at the LHC, as well as with Higgs precision measurements. Our results provide a further motivation for the construction of future e+e- colliders.

submitted time 2016-09-14 Hits846Downloads462 Comment 0

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