A remarkable feature of regenerative processes is their ability to halt proliferation once an organ's structure has been restored. The Wnt signalling pathway is the major driving force for ...homeostatic self-renewal and regeneration in the mammalian intestine. However, the mechanisms that counterbalance Wnt-driven proliferation are poorly understood. Here we demonstrate in mice and humans that yes-associated protein 1 (YAP; also known as YAP1)--a protein known for its powerful growth-inducing and oncogenic properties--has an unexpected growth-suppressive function, restricting Wnt signals during intestinal regeneration. Transgenic expression of YAP reduces Wnt target gene expression and results in the rapid loss of intestinal crypts. In addition, loss of YAP results in Wnt hypersensitivity during regeneration, leading to hyperplasia, expansion of intestinal stem cells and niche cells, and formation of ectopic crypts and microadenomas. We find that cytoplasmic YAP restricts elevated Wnt signalling independently of the AXIN-APC-GSK-3β complex partly by limiting the activity of dishevelled (DVL). DVL signals in the nucleus of intestinal stem cells, and its forced expression leads to enhanced Wnt signalling in crypts. YAP dampens Wnt signals by restricting DVL nuclear translocation during regenerative growth. Finally, we provide evidence that YAP is silenced in a subset of highly aggressive and undifferentiated human colorectal carcinomas, and that its expression can restrict the growth of colorectal carcinoma xenografts. Collectively, our work describes a novel mechanistic paradigm for how proliferative signals are counterbalanced in regenerating tissues. Additionally, our findings have important implications for the targeting of YAP in human malignancies.
Biopolymers are considered a potential alternative to conventional chemical polymers because of their ease of biodegradability, high efficiency, non-toxicity and non-secondary pollution. Recently, ...extracellular polymeric substances (EPS, biopolymers produced by the microorganisms) have been recognised by many researchers as a potential flocculent for their applications in various water, wastewater and sludge treatment processes. In this context, literature information on EPS is widely dispersed and is very scarce. Thus, this review marginalizes various studies conducted so far about EPS nature-production-recovery, properties, environmental applications and moreover, critically examines future research needs and advanced application prospective of the EPS. One of the most important aspect of chemical composition and structural details of different moieties of EPS in terms of carbohydrates, proteins, extracellular DNA, lipid and surfactants and humic substances are described. These chemical characteristics of EPS in relation to formation and properties of microbial aggregates as well as degradation of EPS in the matrix (biomass, flocs etc) are analyzed. The important engineering properties (based on structural characteristics) such as adsorption, biodegradability, hydrophilicity/hydrophobicity of EPS matrix are also discussed in details. Different aspects of EPS production process such as bacterial strain maintenance; inoculum and factors affecting EPS production were presented. The important factors affecting EPS production include growth phase, carbon and nitrogen sources and their ratio, role of other nutrients (phosphorus, micronutrients/trace elements, and vitamins), impact of pH, temperature, metals, aerobic versus anaerobic conditions and pure and mixed culture. The production of EPS in high concentration with high productivity is essential due to economic reasons. Therefore, the knowledge about all the aspects of EPS production (listed above) is highly essential to formulate a logical and scientific basis for the research and industrial activities. One of the very important issues in the production/application/biodegradation of EPS is how the EPS is extracted from the matrix or a culture broth. Moreover, EPS matrix available in different forms (crude, loosely bound, tightly bound, slime, capsular and purified) can be used as a bioflocculant material. Several chemical and physical methods for the extraction of EPS (crude form or purified form) from different sources have been analyzed and reported. There is ample information available in the literature about various EPS extraction methods. Flocculability, dewaterability and biosorption ability are the very attractive engineering properties of the EPS matrix. Recent information on important aspects of these properties qualitatively as well as quantitatively has been described. Recent information on the mechanism of flocculation mediated by EPS is presented. Potential role of EPS in sludge dewatering and biosorption phenomenon has been discussed in details. Different factors influencing the EPS ability to flocculate and dewaterability of different suspensions have been included. The factors considered for the discussion are cations, different forms of EPS, concentration of EPS, protein and carbohydrate content of EPS, molecular weight of EPS, pH of the suspension, temperature etc. These factors were selected for the study based upon their role in the flocculation and dewatering mechanism as well the most recent available literature findings on these factors. For example, only recently it has been demonstrated that there is an optimum EPS concentration for sludge flocculation/dewatering. High or low concentration of EPS can lead to destabilization of flocs. Role of EPS in environmental applications such as water treatment, wastewater flocculation and settling, colour removal from wastewater, sludge dewatering, metal removal and recovery, removal of toxic organic compounds, landfill leachate treatment, soil remediation and reclamation has been presented based on the most recent available information. However, data available on environmental application of EPS are very limited. Investigations are required for exploring the potential of field applications of EPS. Finally, the limitations in the knowledge gap are outlined and the research needs as well as future perspectives are highlighted.
•Bacterial extracellular polymeric substances (EPS) are of bioengineering interest.•Biochemical nature and important properties of EPS were reviewed and discussed.•EPS have attractive engineering properties and they are the potential flocculants.•Important EPS production aspects were critically analysed and thoroughly discussed.•EPS can play important role in several environmental pollution control strategies.
How are skeletal tissues derived from skeletal stem cells? Here, we map bone, cartilage, and stromal development from a population of highly pure, postnatal skeletal stem cells (mouse skeletal stem ...cells, mSSCs) to their downstream progenitors of bone, cartilage, and stromal tissue. We then investigated the transcriptome of the stem/progenitor cells for unique gene-expression patterns that would indicate potential regulators of mSSC lineage commitment. We demonstrate that mSSC niche factors can be potent inducers of osteogenesis, and several specific combinations of recombinant mSSC niche factors can activate mSSC genetic programs in situ, even in nonskeletal tissues, resulting in de novo formation of cartilage or bone and bone marrow stroma. Inducing mSSC formation with soluble factors and subsequently regulating the mSSC niche to specify its differentiation toward bone, cartilage, or stromal cells could represent a paradigm shift in the therapeutic regeneration of skeletal tissues.
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•Bone, cartilage, and stroma are derived from clonal, lineage-restricted progenitors•We defined a postnatal skeletal stem cell (mSSC) and seven downstream progenitors•Skeletal progenitor fate can be directed from bone to cartilage and vice versa•Manipulation of mSSC niche signaling can induce de novo bone or cartilage formation
Bone, cartilage, and stroma development in mice is mapped from a population of postnatal skeletal stem cells to their downstream progenitors of bone, cartilage, and stromal tissue.
Chikungunya virus (CHIKV), an emerging alphavirus, has infected millions of people. However, the factors modulating disease outcome remain poorly understood. Here, we show in germ-free mice or in ...oral antibiotic-treated conventionally housed mice with depleted intestinal microbiomes that greater CHIKV infection and spread occurs within 1 day of virus inoculation. Alteration of the microbiome alters TLR7-MyD88 signaling in plasmacytoid dendritic cells (pDCs) and blunts systemic production of type I interferon (IFN). Consequently, circulating monocytes express fewer IFN-stimulated genes and become permissive for CHIKV infection. Reconstitution with a single bacterial species, Clostridium scindens, or its derived metabolite, the secondary bile acid deoxycholic acid, can restore pDC- and MyD88-dependent type I IFN responses to restrict systemic CHIKV infection and transmission back to vector mosquitoes. Thus, symbiotic intestinal bacteria modulate antiviral immunity and levels of circulating alphaviruses within hours of infection through a bile acid-pDC-IFN signaling axis, which affects viremia, dissemination, and potentially transmission.
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•Perturbation of the intestinal microbiome results in enhanced alphavirus infection•An altered microbiome diminishes type I IFN responses in monocytes and pDCs•Recolonization with a single Clostridium symbiont restores antiviral immunity•Secondary bile acids restore pDC and IFN responses to restrict CHIKV dissemination
Winkler et al. demonstrate that the intestinal microbiome modulates innate immunity to control alphavirus infection of circulating monocytes. Microbiome perturbation dampens TLR7-MyD88 responses in pDCs, blunting type I IFN production and monocyte ISG expression. A single Clostridium species or its associated secondary bile acid restores antiviral responses to inhibit CHIKV infection.
Historically, biological control utilizes predatory species and pathogenic microorganisms to reduce the population of mosquitoes as disease vectors. This is particularly important for the control of ...mosquito-borne arboviruses, which normally do not have specific antiviral therapies available. Although development of resistance is likely, the advantages of biological control are that the resources used are typically biodegradable and ecologically friendly. Over the past decade, the advancement of molecular biology has enabled optimization by the manipulation of genetic materials associated with biological control agents. Two significant advancements are the discovery of cytoplasmic incompatibility induced by Wolbachia bacteria, which has enhanced replacement programs, and the introduction of dominant lethal genes into local mosquito populations through the release of genetically modified mosquitoes. As various arboviruses continue to be significant public health threats, biological control strategies have evolved to be more diverse and become critical tools to reduce the disease burden of arboviruses.
Abstract
We present the second release of value-added catalogues of the LAMOST Spectroscopic Survey of the Galactic Anticentre (LSS-GAC DR2). The catalogues present values of radial velocity Vr, ...atmospheric parameters – effective temperature Teff, surface gravity log g, metallicity Fe/H, α-element to iron (metal) abundance ratio α/Fe (α/M), elemental abundances C/H and N/H and absolute magnitudes MV and $M_{K_{\rm s}}$ deduced from 1.8 million spectra of 1.4 million unique stars targeted by the LSS-GAC since 2011 September until 2014 June. The catalogues also give values of interstellar reddening, distance and orbital parameters determined with a variety of techniques, as well as proper motions and multiband photometry from the far-UV to the mid-IR collected from the literature and various surveys. Accuracies of radial velocities reach 5 km s−1 for the late-type stars, and those of distance estimates range between 10 and 30 per cent, depending on the spectral signal-to-noise ratios. Precisions of Fe/H, C/H and N/H estimates reach 0.1 dex, and those of α/Fe and α/M reach 0.05 dex. The large number of stars, the contiguous sky coverage, the simple yet non-trivial target selection function and the robust estimates of stellar radial velocities and atmospheric parameters, distances and elemental abundances make the catalogues a valuable data set to study the structure and evolution of the Galaxy, especially the solar-neighbourhood and the outer disc.
Purpose
Urbanization and industrialization in China has resulted in a dramatic increase in the volume of wastewater and sewage sludge produced from wastewater treatment plants. Problems associated ...with sewage sludge have attracted increasing attention from the public and urban planners. How to manage sludge in an economically and environmentally acceptable manner is one of the critical issues that modern societies are facing.
Methods
Sludge treatment systems consist of thickening, dewatering, and several different alternative main treatments (anaerobic digestion, aerobic digestion, drying, composting, and incineration). Agricultural application, landfill, and incineration are the principal disposal methods for sewage sludge in China. However, sewage sludge disposal in the future should focus on resource recovery, reducing environmental impacts and saving economic costs.
Results
The reuse of biosolids in all scenarios can be environmentally beneficial and cost-effective. Anaerobic digestion followed by land application is the preferable options due to low economic and energy costs and material reuse.
Conclusion
It is necessary to formulate a standard suitable for the utilization of sewage sludge in China.
The AlCrMoNiTi and AlCrMoZrTi nitride films were prepared by reactive radio-frequency (RF) magnetron sputtering at various N2-to-Ar flow ratios (RN). The influence of RN on the structure and ...properties of these films was investigated. The two alloy films presented an amorphous structure, while a simple face-centered-cubic (FCC) solid-solution structure was observed in the nitride films prepared under different RN. As the RN increased, the clusters, defects and film thickness decreased, which resulted in a dense columnar structure and low surface roughness. Peak hardness of 19.6GPa for AlCrMoZrTi nitride films and 15.4GPa for AlCrMoNiTi nitride films were attained at RN=1.0 respectively. At RN=0.5, the friction coefficients of AlCrMoNiTi and AlCrMoZrTi nitride films were respectively 0.15 and 0.13. Moreover, the AlCrMoZrTi nitride films did not undergo wear-out after 1200s friction experiment. Therefore, The AlCrMoZrTi nitride films exhibited better mechanical properties than that of AlCrMoNiTi nitride films, which may be related to the fact that the solid-solution strengthening effect of Zr was greater than that of Ni.
•Two films were prepared by RF sputtering at various N2/Ar flow ratio (RN).•Two films had an amorphous and FCC phase at low and high RN, respectively.•(AlCrMoZrTi)Nx had the lowest friction coefficient of 0.13 among these films.•The mechanical properties of (AlCrMoZrTi)Nx outperform the (AlCrMoNiTi)Nx.•Solid-solution strengthening effect of Zr element stronger than Ni element.
Abstract
Based on the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) medium-resolution spectroscopic survey (MRS), we report the discovery of nine super Li-rich unevolved stars ...with A(Li) > 3.8 dex. These objects show unusually high levels of lithium abundances, up to three times higher than the meteoritic value of 3.3 dex, which indicates that they must have experienced a history of lithium enrichment. It is found that seven of our program stars are fast rotators with
v
sin
i
> 9 km s
−1
, which suggests that the accretion of circumstellar matter may be the main contributor to the lithium enhancement of these unevolved stars; however, other sources cannot be excluded.
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