A Targeted Deep Sequencing Method to Quantify Endogenous Retrovirus Gag Sequence Variants and Open Reading Frames Expressed in Nonobese Diabetic Mice.

Endogenous retroviruses (ERVs) are involved in autoimmune diseases such as type 1 diabetes (T1D). ERV gene products homologous to murine leukemia retroviruses are expressed in the pancreatic islets of NOD mice, a model of T1D. One ERV gene, Gag, with partial or complete open reading frames (ORFs), is detected in the islets, and it contains many sequence variants. An amplicon deep sequencing analysis was established by targeting a conserved region within the Gag gene to compare NOD with T1D-resistant mice or different ages of prediabetic NOD mice. We observed that the numbers of different Gag variants and ORFs are linked to T1D susceptibility. More importantly, these numbers change during the course of diabetes development and can be quantified to calculate the levels of disease progression. Sequence alignment analysis led to identification of additional markers, including nucleotide mismatching and amino acid consensus at specific positions that can distinguish the early and late stages, before diabetes onset. Therefore, the expression of sequence variants and ORFs of ERV genes, particularly Gag, can be quantified as biomarkers to estimate T1D susceptibility and disease progression.

Broadband tunable laser and infrared camouflage by wavelength-selective scattering metamaterial with radiative thermal management.

Metamaterial-based multispectral (including infrared and multiple lasers) camouflage compatible with non-atmospheric window radiative cooling is effective for low observability against multiple detection means. However, simultaneously achieving low reflectance in a non-atmospheric window band and broadband laser scattering, especially for a broadband tunable long-wave infrared laser, remains challenging. This Letter proposes a wavelength-selective scattering metamaterial (WSSM) that realizes effective camouflage for mid-wave infrared (MWIR), long-wave infrared (LWIR), broadband tunable LWIR and near-infrared (NIR) lasers. Moreover, the WSSM achieves radiative cooling in a non-atmospheric window (5-8 µm). The simulated emissivity is 0.19/0.20 in MWIR and LWIR bands, while it is 0.54 in a non-atmospheric window band that ensures radiative cooling. The WSSM also achieves low specular reflectance (4.35%) in 8-12 µm for broadband tunable laser camouflage, together with low reflectance at 1.06 µm and 1.55 µm. The thermal simulation is also conducted, demonstrating that the WSSM has a surface temperature decrement of 12.6°C compared to the conventional low-emissivity reference at the heated temperature of 400°C due to selective emission. The radiation temperatures have a reduction of 37%/64% than the real surface temperature in MWIR and LWIR bands. This work achieves the multispectral compatible camouflage by regulating specular reflection and scattering, providing a novel, to the best of our knowledge, approach for manipulating electromagnetic waves.

Biomimetic multilayer film simulating solar spectrum reflection characteristics of natural vegetations for optical camouflage.

The camouflage for developed hyperspectral detection technology, which can accurately distinguish the spectrum between object and background, has emerged as an important unsolved challenge. In this study, a biomimetic film (Ge/ZnS multilayer structure) for optical camouflage of hyperspectral and laser with color simulation has been proposed and experimentally demonstrated. By taking advantage of the wavelength selective property of Ge/ZnS multilayer through film interference, the biomimetic film which can simulate the reflection spectral characteristics of vegetation background and eliminate laser signal has been realized based on inverse design. The selective narrowband absorption can manipulate the contrary condition for hyperspectral camouflage (high reflectance in 0.8-1.3 µm) and laser camouflage (low reflectance at 1.06 µm) in the same waveband. The planarized biomimetic multilayer film presents several distinct advantages: (1) elaborate simulation of vegetation reflectance spectrum for hyperspectral camouflage (the spectral similarity coefficient of 92.1%), and efficient absorption at 1.06 µm for laser camouflage (reflectance of 17.8%); (2) tunable color chrominance of various vegetation types for visual camouflage; (3) thermally robust camouflage performance (up to 250 °C) due to temperature endurable property of Ge and ZnS. The hyperspectral-laser camouflage film expands the design strategy of optical camouflage application.

Preparation and Stability of Monodisperse Amorphous CaCO3 Microspheres of High Hardness and Sphericity.

Using amorphous CaCO3 (ACC) to biomimic the crustacean exoskeleton and optimize the physical and chemical properties of the polymeric phase of ACC holds great promise. Controlling the ACC morphology and stability is key in this process. For this article, monodisperse ACC microspheres, with a high sphericity of 0.973 ± 0.001 and a hardness of 0.6755 GPa, were prepared using the gas diffusion method in the presence of Mg2+. Their hardness is 3.58-16 times greater than that ever reported before for ACC microspheres. The stability of ACC is strongly affected by environmental conditions. The liquid phase and high temperature are not conducive to its stability, but ACC microspheres do have high stability under ambient conditions. After 100 days under such conditions, only a small amount of crystallization occurs, and their spherical shape survives intact. This article provides guidance for the preparation of ACC biomimetic composites, sheds light on the biological function of ACC in crustacean exoskeletons, and improves the theoretical understanding of the mechanism of biomineralization.

Type 1 diabetes pathogenesis is modulated by spontaneous autoimmune responses to endogenous retrovirus antigens in NOD mice.

Secreted microvesicles (MVs) are potent inflammatory triggers that stimulate autoreactive B and T cells, causing Type 1 Diabetes in non-obese diabetic (NOD) mice. Proteomic analysis of purified MVs released from islet cells detected the presence of endogenous retrovirus (ERV) antigens, including Env and Gag sequences similar to the well-characterized murine leukemia retroviruses. This raises the possibility that ERV antigens may be expressed in the pancreatic islets via MV secretion. Using virus-like particles produced by co-expressing ERV Env and Gag antigens, and a recombinant gp70 Env protein, we demonstrated that NOD but not diabetes-resistant mice developed anti-Env autoantibodies that increase in titer as disease progresses. A lentiviral-based RNA interference knockdown of Gag revealed that Gag contributes to the MV-induced T-cell response, whose diabetogenic function can be demonstrated via cell-transfer into immune-deficient mice. Finally, we observed that Gag and Env are expressed in NOD islet-derived primary mesenchymal stem cells (MSCs). However, MSCs derived from the islets of diabetes-resistant mice do not express the antigens. Taken together, abnormal ERV activation and secretion of MVs may induce anti-retroviral responses to trigger autoimmunity.

Regulation of myostatin expression is associated with growth and muscle development in commercial broiler and DMC muscle.

Myostatin is a negative regulator of skeletal muscle growth. Muscle tissue is the largest tissue in the body and influences body growth. Commercial Avian broiler chickens are selected for high growth rate and muscularity. Daweishan mini chickens are a slow growing small-sized chicken breed. We investigated the relations between muscle (breast and leg) myostatin mRNA expression and body and muscle growth. Twenty chickens per breed were slaughtered at 0, 30, 60, 90, 120, and 150 days of age. Body and muscle weights were higher at all times in Avian chickens. Breast muscle myostatin expression was higher in Avian chickens than in Daweishan mini chickens at day 30. Myostatin expression peaked at day 60 in Daweishan mini chickens and expression remained higher in breast muscle. Daweishan mini chickens myostatin expression correlated positively with carcass weight, breast and leg muscle weight from day 0 to 60, and correlated negatively with body weight from day 90 to 150, while myostatin expression in Avian chickens was negatively correlated with carcass and muscle weight from day 90 to 150. The results suggest that myostatin expression is related to regulation of body growth and muscle development, with two different regulatory mechanisms that switch between days 30 and 60.

Highly effective biosorption of Sr(II) from low level radioactive wastewater.

Bacillus subtilis was first used to remove Sr(II) from low-level radioactive wastewater. Influence parameters, biosorption kinetics and biosorption equilibrium were investigated. The results showed that the maximum adsorption capacity of Sr(II) at over 2,000 mg g(-1) by Bacillus subtilis was higher than for other biosorbents. At pH 6.3, Sr(II) concentration of 15 mg L(-1), biomass dosage of 0.3 g L(-1) and temperature of 20 °C, the maximum removal efficiency was as high as 96.3% at 1,440 minutes. The biosorption kinetics and the equilibrium isotherm data can be described by the pseudo-second-order equation and Freundlich isotherm equation, respectively. The negative values of ΔG and the positive values of ΔH implied that Sr(II) biosorption on Bacillus subtilis was a spontaneous and endothermic process. Fourier transform infrared spectroscopy indicated that the functional groups, hydroxyl, carboxylate and amide groups, might participate in the interaction between Sr(II) and Bacillus subtilis.

S defect-rich MoS2 aerogel with hierarchical porous structure: Efficient photocatalysis and convenient reuse for removal of organic dyes.

To avoid the difficulty of separating solids from liquids when reusing powder photocatalysts, 3D stereoscopic photocatalysts were constructed. In this study, three-dimensional S defect-rich MoS2 hierarchical aerogel was prepared by chemical cross-linking of functional ultrathin 2D MoS2. Its phase, micro-morphology and structure were characterized, and it was used in the study of photocatalytic degradation of organic pollutants. Of the samples tested, MS@CA-3 (i.e., defect-rich 3D MoS2 aerogel with a loading of 30 mg of defect-rich MoS2) exhibited the best photocatalytic activity due to its suitable load, good light transmission, and a degradation rate of up to 91.0% after 3 h. In addition, MS@CA-3 aerogel offers high recyclability and structural stability, and the degradation rate of the organic pollutant methylene blue decreases only 9.8% after more than ten cycles of photocatalytic degradation. It combines the high catalytic performance of S defect-rich 2D MoS2 and the convenient reusability of hierarchical porous aerogel. This study provides valuable data and a reference for the practical promotion and application of photocatalytic technology in the field of environmental remediation.

Chiral superstructure of aragonite similar to Turritella terebra shell induced by CTAB's adsorption chirality.

A twisted dumbbell-like chiral superstructure can be easily assembled in aragonite under the co-action of CTAB and Mg2+, producing a microstructure that is very similar to that of Turritella terebra shell. Asymmetric adsorption of the CTAB head group on aragonite, namely "adsorption chirality", is the reason for the chiral assembly.

Photocatalytic mechanism conversion of titanium dioxide induced via surface interface coordination.

Photocatalytic removal of organic pollutants is a promising pollution treatment technology from the aspect of carbon neutrality. The complex diversity of actual wastewater components, as opposed to single-component systems, can significantly affect photocatalytic mechanisms. In this study, complex pollutant systems were created using various coordinating agents, and the effects of P25 on the photocatalytic removal of methyl orange (MO) in these systems and corresponding photocatalytic mechanism were investigated. The results show that photocatalytic removal of MO by P25 using ligands is significantly more efficient, especial removal of MO by the EDTA-P25 (P-E2.5) coordination system resulted dramatically improved MO removal (97.4% versus 12.3% achieved by pure P25 after 15 min), with the reaction rate improved 23.8-fold. Theoretical calculations show that the effective coordination bonds formed by the coordinating agent and Ti atoms reduce the adsorption energy of P25 for MO. In addition, introduction of the coordinating agent EDTA reduces the transition state energy during the MO degradation process and greatly accelerates the reaction rate, and the conduction band position of the EDTA-P25 coordination system shifts to a more negative potential, which induces to the generation of •O2- for effective MO degradation.

Tid1 functions as a tumour suppressor in head and neck squamous cell carcinoma.

Human tumourous imaginal disc (Tid1), a human homologue of the Drosophila tumour suppressor protein Tid56, is involved in multiple intracellular signalling pathways such as apoptosis, cell proliferation, and cell survival. Here, we investigated the anti-tumourigenic activity of Tid1 in head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo. Firstly, the clinical association between Tid1 expression and progression of HNSCC was explored. It was found that expression of Tid1 was negatively associated with tumour status, recurrence, and survival prognosis using immunohistochemical analysis of primary HNSCC patient tumour tissue. Secondly, ectopic expression of Tid1 in HNSCC cells was shown to significantly inhibit cell proliferation, migration, invasion, anchorage-independent growth, and xenotransplantation tumourigenicity. Thirdly, we showed that overexpression of Tid1 attenuated EGFR activity and blocked the activation of AKT in HNSCC cells, which are known to be involved in the regulation of survival in HNSCC cells. On the other hand, ectopic expression of constitutively active AKT greatly reduced apoptosis induced by Tid1 overexpression. Together, these findings suggest that Tid1 functions as a tumour suppressor in HNSCC tumourigenesis.

Endogenous retrovirus Gag antigen and its gene variants are unique autoantigens expressed in the pancreatic islets of non-obese diabetic mice.

Endogenous retrovirus (ERV) are remnants of ancient retroviruses that have been incorporated into the genome and evidence suggests that they may play a role in the etiology of T1D. We previously identified a murine leukemia retrovirus-like ERV whose Env and Gag antigens are involved in autoimmune responses in non-obese diabetic (NOD) mice. In this study, we show that the Gag antigen is present in the islet stromal cells. Although Gag gene transcripts were present, Gag protein was not detected in diabetes-resistant mice. Cloning and sequencing analysis of individual Gag genes revealed that NOD islets express Gag gene variants with complete open-reading frames (ORFs), in contrast to the diabetes-resistant mice, whose islet Gag gene transcripts are mostly non-ORFs. Importantly, the ORFs obtained from the NOD islets are extremely heterogenous, coding for various mutants that are absence in the genome. We further show that Gag antigens are stimulatory for autoreactive T cells and identified one islet-expressing Gag variant that contains an altered peptide ligand capable of inducing IFN-gamma release by the T cells. The data highlight a unique retrovirus-like factor in the islets of the NOD mouse strain, which may participate in key events triggering autoimmunity and T1D.

Profiles of expression pattern and tissue distribution of host defense peptides genes in different chicken (Gallus gallus) breeds related to body weight.

Host defense peptides (HDPs) are an important first line of defense with antimicrobial and immunomodulatory properties. Selection for increased body weight is hypothesized to be related to reduced immune response. We studied the relationships among body weight, age, and the HDP expression patterns in intestine and immune organs. We used chickens with marked differences of body sizes. The non-selected Daweishan mini chickens showed the highest indexes of immune organs and the lowest concentrations of the plasma immune parameters C3, C4, IgA, and IgY, while the commercial Avian broiler showed the opposite results. The Daweishan mini chickens showed the highest mRNA expressions of HDP genes in small intestine followed by the semi-selected Wuding chickens. Compared with local breeds, broiler chickens showed higher mRNA expression of HDP genes in spleen, thymus, and bursa. Body weight and HDP expression levels were negatively correlated in the intestine and positively in the immune organs. Our results indicated that the HDP immune regulatory roles in small intestine acted as first line of defense in innate immunity in local breeds, and as an adaptive immunity in broiler chickens. Selection was associated with different expression expressions of HDP genes in breed-, age-, and organ-specific manners.

A synergetic biomineralization strategy for immobilizing strontium during calcification of the coccolithophore Emiliania huxleyi.

The coccolithophore species Emiliania huxleyi has one of the most global distributions in the modern oceans. They are characteristically covered with calcite scales called coccoliths. In this study, stable strontium immobilization during the calcification process was investigated to indirectly assess a proposed bioremediation approach for removing Sr2+ contamination from marine environments. Results indicate that E. huxleyi has high Sr2+ tolerance and removal efficiency in response to Sr2+ stress ranging from 5.6 to 105.6 ppm. Sr2+ immobilization during E. huxleyi calcification indicates a concentration-dependent synergistic mechanism. At lower concentrations of Sr2+ (25.6 ppm), Sr2+ is incorporated into coccoliths through competitive supply between Sr2+ and Ca2+. In addition, calcite productivity decreases with increased Sr2+ removal efficiency due to crystallographic transformation of coccoliths from hydrated calcite into aragonite at 55.6 ppm Sr2+. Further formation of strontianite at 105.6 ppm Sr2+ is due to precipitation of Sr2+ on the edge of the rims and radial arrays of the coccoliths. Our study implies that coccolithophores are capable of significant removal of Sr2+ from the marine environment.

Synergistic interface behavior of strontium adsorption using mixed microorganisms.

The proper handling of low-level radioactive waste is crucial to promote the sustainable development of nuclear power. Research into the mechanism for interactions between bacterium and radionuclides is the starting point for achieving successful remediation of radionuclides with microorganisms. Using Sr(II) as a simulation radionuclide and the mixed microorganisms of Saccharomyces cerevisiae and Bacillus subtilis as the biological adsorbent, this study investigates behavior at the interface between Sr(II) and the microorganisms as well as the mechanisms governing that behavior. The results show that the optimal ratio of mixed microorganisms is S. cerevisiae 2.0 g L-1 to B. subtilis 0.05 g L-1, and the optimal pH is about 6.3. Sr(II) biosorption onto the mixed microorganisms is spontaneous and endothermic in nature. The kinetics and the equilibrium isotherm data of the biosorption process can be described with pseudo-second-order equation and the Langmuir isotherm equation, respectively. The key interaction between the biological adsorbent and Sr(II) involves shared electronic pairs arising from chemical reactions via bond complexation or electronic exchange, and spectral and energy spectrum analysis show that functional groups (e.g., hydroxyl, carboxyl, amino, amide) at the interface between the radionuclide and the mixed microorganisms are the main active sites of the interface reactions.

miR-30 disrupts senescence and promotes cancer by targeting both p16INK4A and DNA damage pathways.

miR-30 is a microRNA frequently overexpressed in human cancers. However, the biological consequence of miR-30 overexpression in cancer has been unclear. In a genetic screen, miR-30 was found to abrogate oncogenic-induced senescence, a key tumor-suppressing mechanism that involves DNA damage responses, activation of p53 and induction of p16INK4A. In cells and mouse models, miR-30 disrupts senescence and promotes cancer by suppressing 2 targets, CHD7 and TNRC6A. We show that while CHD7 is a transcriptional coactivator essential for induction of p16INK4A in senescent cells, TNRC6A, a miRNA machinery component, is required for expression and functionality of DNA damage response RNAs (DDRNAs) that mediate DNA damage responses and p53 activation by orchestrating histone modifications, chromatin remodeling and recruitment of DNA damage factors at damaged sites. Thus, miR-30 inhibits both p16INK4A and p53, 2 key senescence effectors, leading to efficient senescence disruption. These findings have identified novel signaling pathways mediating oncogene-induced senescence and tumor-suppression, and revealed the molecular and cellular mechanisms underlying the oncogenic activity of miR-30. Thus, the miR-30/CHD7/TNRC6A pathway is potentially a novel diagnostic biomarker and therapeutic target for cancer.

Inhibition of retroviral pathogenesis by RNA interference.

BACKGROUND: RNA interference (RNAi) is a newly discovered cellular defense system that is known to suppress replication of genomic parasites in model organisms. It has been widely conjectured that RNAi may also serve as an antiviral system in vertebrates. RESULTS: Retroviral infection could be initiated by electroporation of cloned Rous sarcoma virus (RSV) proviral DNA into the developing chick neural tube. Coelectroporation of proviral DNA and short double-stranded RNAs matching sequences of avain retroviruses, which were designed to induce RNAi against RSV, inhibited viral replication. Replication of RSV after electroporation resulted in disruption of embryonic development and early death, but this, too, could be suppressed by RNAi against the RSV genome. RNAi could also inhibit the growth of RSV and HIV in cell culture. Analysis of the step of the retroviral life cycle that is inhibited by RNAi revealed that it primarily prevented accumulation of the viral RNAs synthesized late during infection. RNA genomes introduced in viral particles early during infection were less sensitive. CONCLUSIONS: RNAi can block retroviral infection in vertebrates. The tissue electroporation method described here should allow RNAi to be used widely to study gene function and control of infection in vertebrate animals.

RNA interference against retroviruses.

Bang and Ellerman, and later Peyton Rous, reported the first identification of transmissible cancer-causing agents, which later turned out to be avian retroviruses. Today avian retroviruses are important models for study of retrovirus replication and pathogenesis, and also important pathogens of domestic fowl. Here we describe the use of RNA interference (RNAi) in live chick embryos to block replication of an avian retrovirus. We also describe inhibition of ASLV and HIV replication in cell culture with RNAi.

A novel function of p38-regulated/activated kinase in endothelial cell migration and tumor angiogenesis.

The p38 mitogen-activated protein kinase (MAPK) pathway has been implicated in both suppression and promotion of tumorigenesis. It remains unclear how these 2 opposite functions of p38 operate in vivo to impact cancer development. We previously reported that a p38 downstream kinase, p38-regulated/activated kinase (PRAK), suppresses tumor initiation and promotion by mediating oncogene-induced senescence in a murine skin carcinogenesis model. Here, using the same model, we show that once the tumors are formed, PRAK promotes the growth and progression of skin tumors. Further studies identify PRAK as a novel host factor essential for tumor angiogenesis. In response to tumor-secreted proangiogenic factors, PRAK is activated by p38 via a vascular endothelial growth factor receptor 2 (VEGFR2)-dependent mechanism in host endothelial cells, where it mediates cell migration toward tumors and incorporation of these cells into tumor vasculature, at least partly by regulating the phosphorylation and activation of focal adhesion kinase (FAK) and cytoskeletal reorganization. These findings have uncovered a novel signaling circuit essential for endothelial cell motility and tumor angiogenesis. Moreover, we demonstrate that the tumor-suppressing and tumor-promoting functions of the p38-PRAK pathway are temporally and spatially separated during cancer development in vivo, relying on the stimulus, and the tissue type and the stage of cancer development in which it is activated.

The epithelial-mesenchymal transition mediator S100A4 maintains cancer-initiating cells in head and neck cancers.

Cancer-initiating cells (CIC) comprise a rare subpopulation of cells in tumors that are proposed to be responsible for tumor growth. Starting from CICs identified in head and neck squamous cell carcinomas (HNSCC), termed head and neck cancer-initiating cells (HN-CIC), we determined as a candidate stemness-maintaining molecule for HN-CICs the proinflammatory mediator S100A4, which is also known to be an inducer of epithelial-mesenchymal transition. S100A4 knockdown in HN-CICs reduced their self-renewal capability and their stemness and tumorigenic properties, both in vitro and in vivo. Conversely, S100A4 overexpression in HNSCC cells enhanced their stem cell properties. Mechanistic investigations indicated that attenuation of endogenous S100A4 levels in HNSCC cells caused downregulation of Notch2 and PI3K (phosphoinositide 3-kinase)/pAKT along with upregulation of PTEN, consistent with biological findings. Immunohistochemical analysis of HNSCC clinical specimens showed that S100A4 expression was positively correlated with clinical grading, stemness markers, and poorer patient survival. Together, our findings reveal a crucial role for S100A4 signaling pathways in maintaining the stemness properties and tumorigenicity of HN-CICs. Furthermore, our findings suggest that targeting S100A4 signaling may offer a new targeted strategy for HNSCC treatment by eliminating HN-CICs.