Ndrg2 regulates vertebral specification in differentiating somites

AbstractIt is generally thought that vertebral patterning and identity are globally determined prior to somite formation. Relatively little is known about the regulators of vertebral specification after somite segmentation. Here, we demonstrated that Ndrg2, a tumor suppressor gene, was dynamically expressed in the presomitic mesoderm (PSM) and at early stage of differentiating somites. Loss of Ndrg2 in mice resulted in vertebral homeotic transformations in thoracic/lumbar and lumbar/sacral transitional regions in a dose-dependent manner. Interestingly, the inactivation of Ndrg2 in osteoblasts or chondrocytes caused defects resembling those observed in Ndrg2−/− mice, with a lower penetrance. In addition, forced overexpression of Ndrg2 in osteoblasts or chondrocytes also conferred vertebral defects, which were distinct from those in Ndrg2−/− mice. These genetic analyses revealed that Ndrg2 modulates vertebral identity in segmented somites rather than in the PSM. At the molecular level, combinatory alterations of the amount of Hoxc8-11 gene transcripts were detected in the differentiating somites of Ndrg2−/− embryos, which may partially account for the vertebral defects in Ndrg2 mutants. Nevertheless, Bmp/Smad signaling activity was elevated in the differentiating somites of Ndrg2−/− embryos. Collectively, our findings unveiled Ndrg2 as a novel regulator of vertebral specification in differentiating somites

Interleukin-10 Inhibits Bone Resorption: A Potential Therapeutic Strategy in Periodontitis and Other Bone Loss Diseases

Periodontitis and other bone loss diseases, decreasing bone volume and strength, have a significant impact on millions of people with the risk of tooth loss and bone fracture. The integrity and strength of bone are maintained through the balance between bone resorption and bone formation by osteoclasts and osteoblasts, respectively, so the loss of bone results from the disruption of such balance due to increased resorption or/and decreased formation of bone. The goal of therapies for diseases of bone loss is to reduce bone loss, improve bone formation, and then keep healthy bone density. Current therapies have mostly relied on longterm medication, exercise, anti-inflammatory therapies, and changing of the life style. However there are some limitations for some patients in the effective treatments for bone loss diseases because of the complexity of bone loss. Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine, and recent studies have indicated that IL-10 can contribute to the maintenance of bone mass through inhibition of osteoclastic bone resorption and regulation of osteoblastic bone formation. This paper will provide a brief overview of the role of IL-10 in bone loss diseases and discuss the possibility of IL-10 adoption in therapy of bone loss diseases therapy

Symmetry-protected higher-order exceptional points in staggered flatband rhombic lattices

Higher-order exceptional points (EPs), which appear as multifold degeneracies in the spectra of non-Hermitian systems, are garnering extensive attention in various multidisciplinary fields. However, constructing higher-order EPs still remains as a challenge due to the strict requirement of the system symmetries. Here we demonstrate that higher-order EPs can be judiciously fabricated in PT -symmetric staggered rhombic lattices by introducing not only on-site gain/loss but also nonHermitian couplings. Zero-energy flatbands persist and symmetry-protected third-order EPs (EP3) arise in these systems owing to the non-Hermitian chiral/sublattice symmetry, but distinct phase transitions and propagation dynamics occur. Specifically, the EP3 arises at the Brillouin zone (BZ) boundary in the presence of on-site gain/loss. The single-site excitations display an exponential power increase in the PT -broken phase. Meanwhile, a nearly flatband sustains when a small lattice perturbation is applied. For the lattices with non-Hermitian couplings, however, the EP3 appears at the BZ center. Quite remarkably, our analysis unveils a dynamical delocalization-localization transition for the excitation of the dispersive bands and a quartic power increase beyond the EP3. Our scheme provides a new platform towards the investigation of the higher-order EPs, and can be further extended to the study of topological phase transitions or nonlinear processes associated with higher-order EPs.Comment: 10 pages, 10 figure

Culture and Hybridization Experiments on an Ulva Clade Including the Qingdao Strain Blooming in the Yellow Sea

In the summer of 2008, immediately prior to the Beijing Olympics, a massive green tide of the genus Ulva covered the Qingdao coast of the Yellow Sea in China. Based on molecular analyses using the nuclear encoded rDNA internal transcribed spacer (ITS) region, the Qingdao strains dominating the green tide were reported to be included in a single phylogenetic clade, currently regarded as a single species. On the other hand, our detailed phylogenetic analyses of the clade, using a higher resolution DNA marker, suggested that two genetically separate entities could be included within the clade. However, speciation within the Ulva clade has not yet been examined. We examined the occurrence of an intricate speciation within the clade, including the Qingdao strains, via combined studies of culture, hybridization and phylogenetic analysis. The two entities separated by our phylogenetic analyses of the clade were simply distinguished as U. linza and U. prolifera morphologically by the absence or presence of branches in cultured thalli. The inclusion of sexual strains and several asexual strains were found in each taxon. Hybridizations among the sexual strains also supported the separation by a partial gamete incompatibility. The sexually reproducing Qingdao strains crossed with U. prolifera without any reproductive boundary, but a complete reproductive isolation to U. linza occurred by gamete incompatibility. The results demonstrate that the U. prolifera group includes two types of sexual strains distinguishable by crossing affinity to U. linza. Species identification within the Ulva clade requires high resolution DNA markers and/or hybridization experiments and is not possible by reliance on the ITS markers alone

Investigation of a novel TBC1D24 variation causing autosomal dominant non-syndromic hearing loss

Abstract Hearing loss is considered one of the most common sensory neurological defects, with approximately 60% of cases attributed to genetic factors. Human pathogenic variants in the TBC1D24 gene are associated with various clinical phenotypes, including dominant nonsyndromic hearing loss DFNA65, characterized by progressive hearing loss after the development of language. This study provides an in-depth analysis of the causative gene and mutations in a family with hereditary deafness. We recruited a three-generation family with autosomal dominant nonsyndromic hearing loss (ADNSHL) and conducted detailed medical histories and relevant examinations. Next-generation sequencing (NGS) was used to identify genetic variants in the proband, which were then validated using Sanger sequencing. Multiple computational software tools were employed to predict the impact of the variant on the function and structure of the TBC1D24 protein. A series of bioinformatics tools were applied to determine the conservation characteristics of the sequence, establish a three-dimensional structural model, and investigate changes in molecular dynamics. A detailed genotype and phenotype analysis were carried out. The family exhibited autosomal dominant, progressive, postlingual, and nonsyndromic sensorineural hearing loss. A novel heterozygous variant, c.1459C>T (p.His487Tyr), in the TBC1D24 gene was identified and confirmed to be associated with the hearing loss phenotype in this family. Conservation analysis revealed high conservation of the amino acid affected by this variant across different species. The mutant protein showed alterations in thermodynamic stability, elasticity, and conformational dynamics. Molecular dynamics simulations indicated changes in RMSD, RMSF, Rg, and SASA of the mutant structure. We computed the onset age of non-syndromic hearing loss associated with mutations in the TBC1D24 gene and identified variations in the hearing progression time and annual threshold deterioration across different frequencies. The identification of a new variant associated with rare autosomal dominant nonsyndromic hereditary hearing loss in this family broadens the range of mutations in the TBC1D24 gene. This variant has the potential to influence the interaction between the TLDc domain and TBC domain, thereby affecting the protein’s biological function

Numerical simulation study of rock breaking mechanism by high voltage electric pulse

High-voltage electric pulse(HVEP)drilling has become a new and efficient rock breaking method, which is also the research focus in the field of drilling speed increase. To probe into rock breaking mechanism of high voltage electric pulse, this study establishes a two-dimensional numerical model of multi-physical field coupling electric breakdown of single pair of electrodes. The model reproduces the generation of plasma channels in homogeneous red sandstone from the coupling of current field, electric breakdown field and circuit field. This paper analyzes the effect of electrode pair angle, voltage and electrode spacing on rock electrical breakdown(that is, the formation of plasma channel in rock). The model includes the circuit structure parameters of pulse tool, the occurrence and development of electrical breakdown, and the relationship between electrical breakdown intensity and time. Results indicate that the plasma channel begins to sprout from the partial area near the top of the discharge electrode and develops towards the partial weak dielectric strength. With the voltage value of loading pulse increasing gradually, the time of electrical breakdown decreases gradually; comparatively, the equivalent failure volume of rock model increases gradually, and there is a positive correlation between them. On the precondition that the rock can be electrically broken, increasing the electrode spacing can improve the rock breaking efficiency of high voltage electric pulse. The equivalent failure volume of rock shows significant fluctuations during the gradual increase of electrode inclination angle of discharge electrode, and its extreme value mostly appears in the range of electrode inclination angle of 35°~ 55°. To further promote the industrial application of high-voltage electric pulse rock breaking, this paper proposes a three-dimensional numerical model of multi-physical field coupling dynamic electric breakdown of red sandstone based on two-dimensional model, reproducing the appearance of the fracture crater in the rock during the rock breaking process with electrode bit. At the same time, the self-designed coaxial electrode bit is selected for experiments of electric breakdown, and the laboratory experimental results of electric breakdown confirm the simulation experimental results