Titanium (Ti) occurs naturally in soils and as highly purified titanium dioxide (TiO2) in many commercial products that have been used for decades. We report for the first time the occurrence, ...characterization, and removal of nano- and larger-sized Ti at wastewater treatment plants (WWTPs). At one WWTP studied in detail, raw sewage contained 100 to nearly 3000 μg Ti/L. Ti larger than 0.7 μm accounted for the majority of the Ti in raw sewage, and this fraction was well removed by WWTP processes. Ti concentrations in effluents from this and several other WWTPs ranged from <5 to 15 μg/L and were nearly all present in the <0.7 μm size fraction. As Ti was removed, it accumulated in settled solids at concentrations ranging from 1 to 6 μg Ti/mg. Ti-containing solids were imaged in sewage, biosolids, and liquid effluent as well as in commercial products containing engineered TiO2. Single nanoparticles plus spherical aggregates (50 nm to a few hundred nanometer in size) composed of sub-50 nm spheres of Ti and oxygen only (presumably TiO2) were observed in all samples. Significantly larger silicate particles containing a mixture of Ti and other metal atoms were also observed in the samples. To support the field work, laboratory adsorption batch and sequencing batch reactor experiments using TiO2 and activated sludge bacteria verified that adsorption of TiO2 onto activated sludge biomass occurs. Monitoring for TiO2 in the environment where WWTP liquid effluent is discharged (rivers, lakes, oceans) or biomass disposed (landfills, agriculture and soil amendments, incinerator off-gas or residuals) will increase our knowledge on the fate and transport of other nanomaterials in the environment.
The prokaryotic type II CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR-associated 9) system is rapidly revolutionizing the field of genetic engineering, allowing ...researchers to alter the genomes of a large range of organisms with relative ease. Experimental approaches based on this versatile technology have the potential to transform the field of cancer genetics. Here, we review current approaches for functional studies of cancer genes that are based on CRISPR-Cas, with emphasis on their applicability for the development of next-generation models of human cancer.
Simulating DNA evolution has been done through coevolution-agnostic probabilistic frameworks for the past 3 decades. The most common implementation is by using the converse of the probabilistic ...approach used to infer phylogenies which, in the simplest form, simulates a single sequence at a time. However, biological systems are multi-genic, and gene products can affect each other's evolutionary paths through coevolution. These crucial evolutionary dynamics still remain to be simulated, and we believe that modelling them can lead to profound insights for comparative genomics.
Here we present CastNet, a genome evolution simulator that assumes each genome is a collection of genes with constantly evolving regulatory interactions in between them. The regulatory interactions produce a phenotype in the form of gene expression profiles, upon which fitness is calculated. A genetic algorithm is then used to evolve a population of such entities through a user-defined phylogeny. Importantly, the regulatory mutations are a response to sequence mutations, thus making a 1-1 relationship between the rate of evolution of sequences and of regulatory parameters. This is, to our knowledge, the first time the evolution of sequences and regulation have been explicitly linked in a simulation, despite there being a multitude of sequence evolution simulators, and a handful of models to simulate Gene Regulatory Network (GRN) evolution. In our test runs, we see a coevolutionary signal among genes that are active in the GRN, and neutral evolution in genes that are not included in the network, showing that selective pressures imposed on the regulatory output of the genes are reflected in their sequences.
We believe that CastNet represents a substantial step for developing new tools to study genome evolution, and more broadly, coevolutionary webs and complex evolving systems. This simulator also provides a new framework to study molecular evolution where sequence coevolution has a leading role.
Whereas materials with intrinsic magnetoelectric (ME) effects have not yet made inroads in technology, the measurement of their tensor characteristics has become a precious tool for magnetic point ...group determination. Therefore, it is worthwhile to consider different measurement techniques. In particular techniques for determining the linear and bilinear ME effects will be discussed, essentially the quasi-static and dynamic magnetic field-induced methods will be evaluated. The measurement and application of ME “butterfly" loops for determining (weak) ferromagnetism and internal bias fields will be described. For the bilinear ME effect (with invariant EHH) a particularly sensitive measurement method with amplification effect will be highlighted, permitting, e.g., to detect subtle magnetic phase transitions. At least for the linear ME effect, we will stress that in the future only a dimensionless quantity should be used which is valid in all systems of units. Finally, the linear ME effect of TbPO
4
crystals is reexamined because in a former publication it was not clear which system of units was effectively used (“rationalized” or “not rationalized” Gaussian system of units). Effectively, this crystal has the largest linear ME effect known. At T = 1.50 K, in SI units:
α
xy
or
α
yx
= 730 ps/m, i.e., 0.220 in “not rationalized” Gaussian system of units.
Women with polycystic ovary syndrome (PCOS) have reproductive and metabolic abnormalities that result in an increased risk of infertility, diabetes and cardiovascular disease. The large intestine ...contains a complex community of microorganisms (the gut microbiome) that is dysregulated in humans with obesity and type 2 diabetes. Using a letrozole-induced PCOS mouse model, we demonstrated significant diet-independent changes in the gut microbial community, suggesting that gut microbiome dysbiosis may also occur in PCOS women. Letrozole treatment was associated with a time-dependent shift in the gut microbiome and a substantial reduction in overall species and phylogenetic richness. Letrozole treatment also correlated with significant changes in the abundance of specific Bacteroidetes and Firmicutes previously implicated in other mouse models of metabolic disease in a time-dependent manner. Our results suggest that the hyperandrogenemia observed in PCOS may significantly alter the gut microbiome independently of diet.
The coronavirus disease 2019 (COVID-19) pandemic has claimed the lives of over one million people worldwide. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a ...member of the Coronaviridae family of viruses that can cause respiratory infections of varying severity. The cellular host factors and pathways co-opted during SARS-CoV-2 and related coronavirus life cycles remain ill defined. To address this gap, we performed genome-scale CRISPR knockout screens during infection by SARS-CoV-2 and three seasonal coronaviruses (HCoV-OC43, HCoV-NL63, and HCoV-229E). These screens uncovered host factors and pathways with pan-coronavirus and virus-specific functional roles, including major dependency on glycosaminoglycan biosynthesis, sterol regulatory element-binding protein (SREBP) signaling, bone morphogenetic protein (BMP) signaling, and glycosylphosphatidylinositol biosynthesis, as well as a requirement for several poorly characterized proteins. We identified an absolute requirement for the VMP1, TMEM41, and TMEM64 (VTT) domain-containing protein transmembrane protein 41B (TMEM41B) for infection by SARS-CoV-2 and three seasonal coronaviruses. This human coronavirus host factor compendium represents a rich resource to develop new therapeutic strategies for acute COVID-19 and potential future coronavirus pandemics.
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•Genome-wide CRISPR screens for SARS-CoV-2 and seasonal coronavirus host factors•Identification of host factors and pathways with pan-coronavirus and discrete roles•Coronaviruses co-opt multiple biological pathways•TMEM41B is a critical pan-coronavirus host factor
Schneider et al. conducted parallel genome-wide CRISPR knockout screens with SARS-CoV-2 and three seasonal coronaviruses to identify pan-coronavirus and virus-specific host factor requirements. They identified an interconnected network of host factors required by these four viruses and validated TMEM41B as a pan-coronavirus host factor required for a post-entry step in the coronavirus life cycle.
Cancer is a multistep process that involves mutations and other alterations in oncogenes and tumour suppressor genes. Genome sequencing studies have identified a large collection of genetic ...alterations that occur in human cancers. However, the determination of which mutations are causally related to tumorigenesis remains a major challenge. Here we describe a novel CRISPR/Cas9-based approach for rapid functional investigation of candidate genes in well-established autochthonous mouse models of cancer. Using a Kras(G12D)-driven lung cancer model, we performed functional characterization of a panel of tumour suppressor genes with known loss-of-function alterations in human lung cancer. Cre-dependent somatic activation of oncogenic Kras(G12D) combined with CRISPR/Cas9-mediated genome editing of tumour suppressor genes resulted in lung adenocarcinomas with distinct histopathological and molecular features. This rapid somatic genome engineering approach enables functional characterization of putative cancer genes in the lung and other tissues using autochthonous mouse models. We anticipate that this approach can be used to systematically dissect the complex catalogue of mutations identified in cancer genome sequencing studies.
AlxCoCrFeMnNi high-entropy alloys with different aluminum concentrations (x = 0.5, 1, and 1.5 at%) were synthesized by mechanical alloying followed by consolidation using two different sintering ...methods, conventional (CS) and high-frequency induction heat + conventional (HFIHS + CS). The results show the presence of FCC, BCC, and B2ordered phases in all systems, regardless of the sintering method. The BCC phase exhibits morphological changes (cuboidal-type and plate-like) associated with the two sintering methods involving different diffusion rates and affecting the hardness values. The M23C6 carbide is identified in systems sintered by the CS method; meanwhile, the M7C3 carbide is identified in the HFIHS + CS method. Finally, the HFIHS + CS method results in a higher level of densification (~95%) than the CS method (~80%).
•AlxCoCrFeMnNi (x = 0.5, 1 and 1.5 at%) HEAs present B2ordered and FCC phases•BCC phase precipitates from B2ordered phase in Alx (x = 1 and 1.5 at%)•Precipitates (BCC) with cuboidal and plate-like morphology are observed•The coarsening kinetics of the BCC phase is dependent on the sintering method•The HFIHS + CS achieves higher densification than the CS and HFIHS alone
The purpose of this narrative review is to describe the current use environment of both natural and synthetic cannabinoids while providing context for cannabinoid chemistry and pharmacology. In ...addition to a long history of recreational and nonmedical use, natural cannabinoids are increasingly used as prescription products, through medical cannabis programs, and as consumer health products. Despite anecdotal safety evidence, cannabis and cannabinoids are pharmacologically complex and pose risks for adverse drug events and drug-drug interactions. Synthetic cannabinoids, particularly agonists of cannabinoid receptors, are more potent than natural cannabinoids and can lead to more severe reactions and medical emergencies. This review provides a summary of approved uses and an overview of mechanisms of action for adverse drug events with natural and synthetic cannabinoids. Clinical considerations for special populations that may be at heightened risk for drug-drug interactions and adverse drug events while using natural or synthetic cannabinoids are examined, and recommendations are provided.
•The vapor pressure, polar or non-polar nature, and type of milling affect the PSD.•The O and C are incorporated as interstitial elements into the crystalline lattice.•In wet milling, the formation ...of the BCC structure is related to Al content.•In dry milling, the formation of the BCC structure is related to collision energy.•FCC-BCC region is broader in the Al1.5 system than those values calculated by VEC.
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This paper reports the effects of different process control agents (PCA) (methanol, n-heptane, and stearic acid) and aluminum concentration (x = 0.5, 1.0, and 1.5 at%) on the particle size distribution, structure, microstructure, stability, and prediction of phases in AlxCoCrFeMnNi high-entropy powder synthesized by mechanical alloying. The results showed that the vapor pressure, the polar nature of the different process control agents used, and type of milling (dry/wet) generating changes in the particle size distribution, microstructure, and crystalline structure since the use of PCA modifies the balance between the cold-welding and fracture processes. Quantitative analysis showed that the PCA chemical decomposition generated residual oxygen and carbon in all systems. X-ray diffraction showed that all systems present a mixture of crystal structures BCC-FCC with nanometric crystallite size, and the peak intensities changed in function of lattice deformation generated by type milling employed. On the other hand, the results also showed that the boundary between BCC-FCC and FCC regions is even broader and extends to higher Al concentration than those reported by the valence electron concentration criterion.
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