A screening analysis of the GJB2 c.176 del 16 mutation responsible for hereditary deafness in a Chinese family

AbstractObjectiveTo determine whether a new-born child from a family carrying a deafness gene needs cochlear implantation to avoid dysphonia by screening and sequencing a deafness-related gene.ResultsBoth screening and sequencing results confirmed that the new born child had a normal GJB2 gene despite the fact that she has a brother suffering from hearing loss triggered by an allelic GJB2 c.176 del 16 mutation. We cloned the GJB2 genes derived from their respective blood genomic DNA into GFP fused plasmids and transfected those plasmids into the 293T cell line to test for gene function. While the mutated GJB2 gene (GJB2 c.176 del 16) of her deaf brother was found to be unable to form the gap junction structure between two adjacent cells, the baby girl's GJB2 gene ran into no such problems.ConclusionThe screening and sequencing as well as the GJB2 gene function tests invariably showed results consistent with the ABR tested hearing phenotype, which means that the child, with a normal wild type GJB2 gene, does not need early intervention to prevent her from developing hearing loss and dysphonia at a later stage in life

YAO is a nucleolar WD40-repeat protein critical for embryogenesis and gametogenesis in Arabidopsis

<p>Abstract</p> <p>Background</p> <p>In flowering plants, gametogenesis generates multicellular male and female gametophytes. In the model system Arabidopsis, the male gametophyte or pollen grain contains two sperm cells and a vegetative cell. The female gametophyte or embryo sac contains seven cells, namely one egg, two synergids, one central cell and three antipodal cells. Double fertilization of the central cell and egg produces respectively a triploid endosperm and a diploid zygote that develops further into an embryo. The genetic control of the early embryo patterning, especially the initiation of the first zygotic division and the positioning of the cell plate, is largely unknown.</p> <p>Results</p> <p>Here we report the characterization of a mutation, <it>yaozhe (yao)</it>, that causes zygote arrest and misplacement of cell plate of the zygote, leading to early embryo lethality. In addition, gametophyte development is partially impaired. A small portion of the mutant embryo sacs are arrested at four-nucleate stage with aberrant nuclear positioning. Furthermore, the competence of male gametophytes is also compromised. <it>YAO </it>encodes a nucleolar protein with seven WD-repeats. Its homologues in human and yeast have been shown to be components of the U3 snoRNP complex and function in 18S rRNA processing. <it>YAO </it>is expressed ubiquitously, with high level of expression in tissues under active cell divisions, including embryo sacs, pollen, embryos, endosperms and root tips.</p> <p>Conclusions</p> <p>Phenotypic analysis indicated that <it>YAO </it>is required for the correct positioning of the first zygotic division plane and plays a critical role in gametogenesis in Arabidopsis. Since YAO is a nucleolar protein and its counterparts in yeast and human are components of the U3 snoRNP complex, we therefore postulate that YAO is most likely involved in rRNA processing in plants as well.</p

Neoadjuvant SBRT combined with immunotherapy in NSCLC: from mechanisms to therapy

The utilisation of neoadjuvant immunotherapy has demonstrated promising preliminary clinical outcomes for early-stage resectable non-small-cell lung cancer (NSCLC). Nevertheless, it is imperative to develop novel neoadjuvant combination therapy regimens incorporating immunotherapy to further enhance the proportion of patients who derive benefit. Recent studies have revealed that stereotactic body radiotherapy (SBRT) not only induces direct tumour cell death but also stimulates local and systemic antitumour immune responses. Numerous clinical trials have incorporated SBRT into immunotherapy for advanced NSCLC, revealing that this combination therapy effectively inhibits local tumour growth while simultaneously activating systemic antitumour immune responses. Consequently, the integration of SBRT with neoadjuvant immunotherapy has emerged as a promising strategy for treating resectable NSCLC, as it can enhance the systemic immune response to eradicate micrometastases and recurrent foci post-resection. This review aims to elucidate the potential mechanism of combination of SBRT and immunotherapy followed by surgery and identify optimal clinical treatment strategies. Initially, we delineate the interplay between SBRT and the local tumour immune microenvironment, as well as the systemic antitumour immune response. We subsequently introduce the preclinical foundation and preliminary clinical trials of neoadjuvant SBRT combined with immunotherapy for treating resectable NSCLC. Finally, we discussed the optimal dosage, schedule, and biomarkers for neoadjuvant combination therapy in its clinical application. In conclusion, the elucidation of potential mechanism of neoadjuvant SBRT combined immunotherapy not only offers a theoretical basis for ongoing clinical trials but also contributes to determining the most efficacious therapy scheme for future clinical application

Application of decellularized vascular matrix in small-diameter vascular grafts

Coronary artery bypass grafting (CABG) remains the most common procedure used in cardiovascular surgery for the treatment of severe coronary atherosclerotic heart disease. In coronary artery bypass grafting, small-diameter vascular grafts can potentially replace the vessels of the patient. The complete retention of the extracellular matrix, superior biocompatibility, and non-immunogenicity of the decellularized vascular matrix are unique advantages of small-diameter tissue-engineered vascular grafts. However, after vascular implantation, the decellularized vascular matrix is also subject to thrombosis and neoplastic endothelial hyperplasia, the two major problems that hinder its clinical application. The keys to improving the long-term patency of the decellularized matrix as vascular grafts include facilitating early endothelialization and avoiding intravascular thrombosis. This review article sequentially introduces six aspects of the decellularized vascular matrix as follows: design criteria of vascular grafts, components of the decellularized vascular matrix, the changing sources of the decellularized vascular matrix, the advantages and shortcomings of decellularization technologies, modification methods and the commercialization progress as well as the application prospects in small-diameter vascular grafts

The Dust Attenuation Scaling Relation of Star-Forming Galaxies in the EAGLE Simulations

Dust attenuation in star-forming galaxies (SFGs), as parameterized by the infrared excess (IRX $\equiv L_{\rm IR}/L_{\rm UV}$), is found to be tightly correlated with star formation rate (SFR), metallicity and galaxy size, following a universal IRX relation up to $z=3$. This scaling relation can provide a fundamental constraint for theoretical models to reconcile galaxy star formation, chemical enrichment, and structural evolution across cosmic time. We attempt to reproduce the universal IRX relation over $0.1\leq z\leq 2.5$ using the EAGLE hydrodynamical simulations and examine sensitive parameters in determining galaxy dust attenuation. Our findings show that while the predicted universal IRX relation from EAGLE approximately aligns with observations at $z\leq 0.5$, noticeable disparities arise at different stellar masses and higher redshifts. Specifically, we investigate how modifying various galaxy parameters can affect the predicted universal IRX relation in comparison to the observed data. We demonstrate that the simulated gas-phase metallicity is the critical quantity for the shape of the predicted universal IRX relation. We find that the influence of the infrared luminosity and infrared excess is less important while galaxy size has virtually no significant effect. Overall, the EAGLE simulations are not able to replicate some of the observed characteristics between IRX and galaxy parameters of SFGs, emphasizing the need for further investigation and testing for our current state-of-the-art theoretical models.Comment: 19 pages, 15 figures, accepted for publication in MNRA

Systematic biases in determining dust attenuation curves through galaxy SED fitting

While the slope of the dust attenuation curve ($\delta$) is found to correlate with effective dust attenuation ($A_V$) as obtained through spectral energy distribution (SED) fitting, it remains unknown how the fitting degeneracies shape this relation. We examine the degeneracy effects by fitting SEDs of a sample of local star-forming galaxies (SFGs) selected from the Galaxy And Mass Assembly survey, in conjunction with mock galaxy SEDs of known attenuation parameters. A well-designed declining starburst star formation history is adopted to generate model SED templates with intrinsic UV slope ($\beta_0$) spanning over a reasonably wide range. The best-fitting $\beta_0$ for our sample SFGs shows a wide coverage, dramatically differing from the limited range of $\beta_0<-2.2$ for a starburst of constant star formation. Our results show that strong degeneracies between $\beta_0$, $\delta$, and $A_V$ in the SED fitting induce systematic biases leading to a false $A_V$--$\delta$ correlation. Our simulation tests reveal that this relationship can be well reproduced even when a flat $A_V$--$\delta$ relation is taken to build the input model galaxy SEDs. The variations in best-fitting $\delta$ are dominated by the fitting errors. We show that assuming a starburst with constant star formation in SED fitting will result in a steeper attenuation curve, smaller degeneracy errors, and a stronger $A_V$--$\delta$ relation. Our findings confirm that the $A_V$--$\delta$ relation obtained through SED fitting is likely driven by the systematic biases induced by the fitting degeneracies between $\beta_0$, $\delta$, and $A_V$.Comment: 21 pages, 13 figures, accepted for publication in the MNRAS, Comments welcome

The Physical Properties of Star-Forming Galaxies with Strong [O III] Lines at z=3.25

We present an analysis of physical properties of 34 [O III] emission-line galaxies (ELGs) at z=3.254$\pm$0.029 in the Extended Chandra Deep Field South (ECDFS). These ELGs are selected from deep narrow H2S(1) and broad Ks imaging of 383 arcmin$^{2}$ obtained with CFHT/WIRCam. We construct spectral energy distributions (SEDs) from U to Ks to derive the physical properties of ELGs. These [O III] ELGs are identified as starburst galaxies with strong [O III] lines of L([O III]) ~ 10$^{42.6}$ - 10$^{44.2}$ erg s$^{-1}$, and have stellar masses of M* ~ 10$^{9.0}$-10$^{10.6}$ M$_\odot$ and star formation rates of ~ 10-210 M$_\odot$ yr$^{-1}$. Our results show that 24% of our sample galaxies are dusty with Av > 1 mag and EW(OIII)$_{rest}$ ~ 70-500 $\AA$, which are often missed in optically selected [O III] ELG samples. Their rest-frame UV and optical morphologies from HST/ACS and HST/WFC3 deep imaging reveal that these [O III] ELGs are mostly multiple-component systems (likely mergers) or compact. And 20% of them are nearly invisible in the rest-frame UV owing to heavy dust attenuation. Interestingly, we find that our samples reside in an overdensity consisting of two components: one southeast (SE) with an overdensity factor of $\delta_{gal}$ ~ 41 over a volume of 13$^{3}$ cMpc$^{3}$ and the other northwest (NW) with $\delta_{gal}$ ~ 38 over a volume of 10$^{3}$ cMpc$^{3}$. The two overdense substructures are expected to be virialized at z=0 with a total mass of ~ 1.1 x 10$^{15}$ M$_\odot$ and ~ 4.8 x 10$^{14}$ M$_\odot$, and probably merge into a Coma-like galaxy cluster.Comment: 22 pages, 11 figures, 3 tables. Accepted for publication in Ap