Stability of delayed virus infection model with a general incidence rate and adaptive immune response

We present the dynamical behaviors of a virus infection model with general infection rate, immune responses and two intracellular delays which describe the interactions of the HIV virus, target cells, CTL cells and antibodies within host. Three factors are incorporated in this model: (1) the intrinsic growth rate of uninfected cells, (2) a nonlinear incidence rate function considering both virus-tocell infection and cell-to-cell transmission, and (3) a nonlinear productivity and removal function. By the method of Lyapunov functionals and LaSalle’s invariance principle, we show that the global dynamics of the model is determined by the reproductive numbers for viral infection R0, for antibody immune response R1, for CTL immune response R2, for CTL immune competition R3 and for antibody immune competition R4. The numerical simulations are given to illustrate our theoretical results

Whole-exome sequencing study of hypospadias

Summary: Hypospadias results from the impaired urethral development, which is influenced by androgens, but its genetic etiology is still unknown. Through whole exome sequencing analysis, we identified NR5A1, SRD5A2, and AR as mutational hotspots in the etiology of severe hypospadias, as these genes are related to androgen signaling. Additionally, rare damaging variants in cilia-related outer dynein arm heavy chain (ODNAH) genes (DNAH5, DNAH8, DNAH9, DNAH11, and DNAH17) (p = 8.5 × 10−47) were significantly enriched in hypospadias cases. The Dnah8 KO mice exhibited significantly decreased testosterone levels, which had an impact on urethral development and disrupted steroid biosynthesis. Combined with trios data, transcriptomic, and phenotypical and proteomic characterization of a mouse model, our work links ciliary genes with hypospadias. Overall, a panel of ODNAH genes with rare damaging variants was identified in 24% of hypospadias patients, providing significant insights into the underlying pathogenesis of hypospadias as well as genetic counseling

Inactivation of STAT3 Signaling Impairs Hair Cell Differentiation in the Developing Mouse Cochlea

Although STAT3 signaling is demonstrated to regulate sensory cell differentiation and regeneration in the zebrafish, its exact role is still unclear in mammalian cochleae. Here, we report that STAT3 and its activated form are specifically expressed in hair cells during mouse cochlear development. Importantly, conditional cochlear deletion of Stat3 leads to an inhibition on hair cell differentiation in mice in vivo and in vitro. By cell fate analysis, inactivation of STAT3 signaling shifts the cell division modes from asymmetric to symmetric divisions from supporting cells. Moreover, inhibition of Notch signaling stimulates STAT3 phosphorylation, and inactivation of STAT3 signaling attenuates production of supernumerary hair cells induced by a Notch pathway inhibitor. Our findings highlight an important role of the STAT3 signaling during mouse cochlear hair cell differentiation and may have clinical implications for the recovery of hair cell loss-induced hearing impairment