The Influence of ALS-associated MATR3 Toxicity on Cell Size in the Yeast Model

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease1. The pathology of ALS is described as the progressive degeneration of motor neurons that initially leads to atrophy of the voluntary muscles followed by the involuntary muscles1,2. Ultimately, the cause of death is pulmonary distress due to loss of function of the diaphragm2. Life expectancy after diagnosis is usually one year, and there are currently no cures or effective treatments for this fatal disease3. Approximately 90% of all ALS cases are sporadic meaning that the disease is developed randomly, while around 10% of the cases are familial meaning that the disease is passed down within a family3,4. Over 30 years, many genes have been identified and linked to the development of familial ALS. One of these genes is MATR3 which codes for Matrin-3, a nuclear matrix protein that binds to DNA and RNA with various roles in the nucleus5. Matrin-3 is normally found in the nucleus; however, when the gene is mutated, Matrin-3 is depleted from the nucleus and accumulates in clusters in the cytoplasm6. Matrin-3 associated toxicity is hypothesized to be either due to the loss of function of the protein in the nucleus or a gain of toxicity function in the cytoplasm leading to neuronal cell death. Furthermore, with increasing MATR3 toxicity in yeast, an increase in cell size was observed

Strength distribution of cemented waste rock backfill: a similarity simulation experiment

Backfill of cemented waste rock into underground mined-out areas is an effective way to eliminate solid wastes and potential hazards in mines. To understand the backfill strength distribution law throughout the stope, similarity simulation experiments were conducted for direct-irrigating cemented waste rock backfill, and OpenCV and neural network were employed to analyze particle segregation and the spatial distribution of backfill strength. Results show that distinct gravitational segregation leads to an uneven and heterogeneous distribution of natural graded waste rocks in a similar model. Backfill strength near sidewalls and bottom of the model surpasses that of other areas. In the vertical direction, the average backfill strength increases with depth, ranging from 1.15 MPa at the topmost layer to 1.91 MPa at the bottommost layer. Horizontally, the average backfill strength near model boundaries is consistently higher than that at the model center, irrespective of the layer depth and orientation. Neural network prediction on spatial backfill strength proves reliable, exhibiting an average relative error of 4.12%, compared to the traditional surface fitting with a 10.20% error. Verification tests affirm the capability of the neural network model to accurately predict the anisotropic and nonlinear distribution of backfill strength in a large stope

OsHAC1;1 and OsHAC1;2 function as arsenate reductases and regulate arsenic accumulation

Rice is a major dietary source of the toxic metalloid arsenic (As). Reducing its accumulation in rice (Oryza sativa) grain is of critical importance to food safety. Rice roots take up arsenate and arsenite depending on the prevailing soil conditions. The first step of arsenate detoxification is its reduction to arsenite, but the enzyme(s) catalyzing this reaction in rice remains unknown. Here, we identify OsHAC1;1 and OsHAC1;2 as arsenate reductases in rice. OsHAC1;1 and OsHAC1;2 are able to complement an Escherichia coli mutant lacking the endogenous arsenate reductase and to reduce arsenate to arsenite. OsHAC1:1 and OsHAC1;2 are predominantly expressed in roots, with OsHAC1;1 being abundant in the epidermis, root hairs, and pericycle cells while OsHAC1;2 is abundant in the epidermis, outer layers of cortex, and endodermis cells. Expression of the two genes was induced by arsenate exposure. Knocking out OsHAC1;1 or OsHAC1;2 decreased the reduction of arsenate to arsenite in roots, reducing arsenite efflux to the external medium. Loss of arsenite efflux was also associated with increased As accumulation in shoots. Greater effects were observed in a double mutant of the two genes. In contrast, overexpression of either OsHAC1;1 or OsHAC1;2 increased arsenite efflux, reduced As accumulation, and enhanced arsenate tolerance. When grown under aerobic soil conditions, overexpression of either OsHAC1;1 or OsHAC1;2 also decreased As accumulation in rice grain, whereas grain As increased in the knockout mutants. We conclude that OsHAC1;1 and OsHAC1;2 are arsenate reductases that play an important role in restricting As accumulation in rice shoots and grain

Prevalence of porcine circovirus-like agent P1 in Jiangsu, China

Recently, we identified a novel porcine circovirus type 2-like agent P1 isolate from swine. The present study represents the first survey of P1 prevalence in swine herds from Jiangsu, China, by using PCR targeting the complete genome of P1. Prevalences of 50% and 19% were found among 6 herds and 248 animals, respectively. The results indicate a high prevalence of P1 in China pig populations

Research progress on degradative solvent extraction of low-rank coals

The degradative solvent extraction of low rank coal is the use of solvents to extract low rank coal under mild conditions, through the dehydration and multi-stage separation of the raw coal： the extraction products with no water content, no ash content, high calorific value properties and excellent thermoplastic properties， and low moisture of the extractive residual coal can be obtained. At the same time, the products have practical application advantages in many fields such as coal coking, advanced fuel and carbon material preparation, which have high added value, and the solvent in this technology has the advantage of being recyclable. Therefore, degradative solvent extraction is one of the effective ways to realize the graded fractionated conversion and utilization of low-rank coal. This review firstly introduces the existing low rank coal upgrading methods, and then reviews the development of degradative solvent extraction, focusing on the various influencing factors, reaction mechanisms, existing processes and product utilization of low rank coal upgrading by degradative solvent extraction. Finally, using the "Web of Science core collection" as the data source, the knowledge graph of coal solvent extraction was carved using CiteSpace scientometric software, and the research themes were analyzed to summarize the research directions and predict the research hotspots, providing some reference value for the research of degradative solution extraction of low-rank coal. The comprehensive analysis shows that: the selection of new low-cost green solvents, structural characterization and high-value utilization of extraction products have high research trends, while in-depth research on extraction mechanism and targeted regulation of extractant properties is needed to further promote the process of large-scale production

Transcriptional Homeostasis of a Mangrove Species, Ceriops tagal, in Saline Environments, as Revealed by Microarray Analysis

<div><h3>Background</h3><p>Differential responses to the environmental stresses at the level of transcription play a critical role in adaptation. Mangrove species compose a dominant community in intertidal zones and form dense forests at the sea-land interface, and although the anatomical and physiological features associated with their salt-tolerant lifestyles have been well characterized, little is known about the impact of transcriptional phenotypes on their adaptation to these saline environments.</p> <h3>Methodology and Principal findings</h3><p>We report the time-course transcript profiles in the roots of a true mangrove species, <em>Ceriops tagal</em>, as revealed by a series of microarray experiments. The expression of a total of 432 transcripts changed significantly in the roots of <em>C. tagal</em> under salt shock, of which 83 had a more than 2-fold change and were further assembled into 59 unigenes. Global transcription was stable at the early stage of salt stress and then was gradually dysregulated with the increased duration of the stress. Importantly, a pair-wise comparison of predicted homologous gene pairs revealed that the transcriptional regulations of most of the differentially expressed genes were highly divergent in <em>C. tagal</em> from that in salt-sensitive species, <em>Arabidopsis thaliana</em>.</p> <h3>Conclusions/Significance</h3><p>This work suggests that transcriptional homeostasis and specific transcriptional regulation are major events in the roots of <em>C. tagal</em> when subjected to salt shock, which could contribute to the establishment of adaptation to saline environments and, thus, facilitate the salt-tolerant lifestyle of this mangrove species. Furthermore, the candidate genes underlying the adaptation were identified through comparative analyses. This study provides a foundation for dissecting the genetic basis of the adaptation of mangroves to intertidal environments.</p> </div

A Yeast Model of FUS/TLS-Dependent Cytotoxicity

FUS/TLS is a nucleic acid binding protein that, when mutated, can cause a subset of familial amyotrophic lateral sclerosis (fALS). Although FUS/TLS is normally located predominantly in the nucleus, the pathogenic mutant forms of FUS/TLS traffic to, and form inclusions in, the cytoplasm of affected spinal motor neurons or glia. Here we report a yeast model of human FUS/TLS expression that recapitulates multiple salient features of the pathology of the disease-causing mutant proteins, including nuclear to cytoplasmic translocation, inclusion formation, and cytotoxicity. Protein domain analysis indicates that the carboxyl-terminus of FUS/TLS, where most of the ALS-associated mutations are clustered, is required but not sufficient for the toxicity of the protein. A genome-wide genetic screen using a yeast over-expression library identified five yeast DNA/RNA binding proteins, encoded by the yeast genes ECM32, NAM8, SBP1, SKO1, and VHR1, that rescue the toxicity of human FUS/TLS without changing its expression level, cytoplasmic translocation, or inclusion formation. Furthermore, hUPF1, a human homologue of ECM32, also rescues the toxicity of FUS/TLS in this model, validating the yeast model and implicating a possible insufficiency in RNA processing or the RNA quality control machinery in the mechanism of FUS/TLS mediated toxicity. Examination of the effect of FUS/TLS expression on the decay of selected mRNAs in yeast indicates that the nonsense-mediated decay pathway is probably not the major determinant of either toxicity or suppression.Fidelity Biosciences (Firm)Fidelity Biosciences (Firm) (Research Inititative)ALS Therapy AllianceNational Institutes of Health (U.S.) (NIH 1RC1NS06839)National Institutes of Health (U.S.) (NIH U01NS05225-03)National Institutes of Health (U.S.) (NIH R01NS050557-05)National Institutes of Health (U.S.) (NIH 1RC2NS070342-01)Pierre L. de Bourgknecht ALS Research FoundationNational Science Foundation (U.S.) (NS614192

Neutrino Physics with JUNO

The Jiangmen Underground Neutrino Observatory (JUNO), a 20 kton multi-purposeunderground liquid scintillator detector, was proposed with the determinationof the neutrino mass hierarchy as a primary physics goal. It is also capable ofobserving neutrinos from terrestrial and extra-terrestrial sources, includingsupernova burst neutrinos, diffuse supernova neutrino background, geoneutrinos,atmospheric neutrinos, solar neutrinos, as well as exotic searches such asnucleon decays, dark matter, sterile neutrinos, etc. We present the physicsmotivations and the anticipated performance of the JUNO detector for variousproposed measurements. By detecting reactor antineutrinos from two power plantsat 53-km distance, JUNO will determine the neutrino mass hierarchy at a 3-4sigma significance with six years of running. The measurement of antineutrinospectrum will also lead to the precise determination of three out of the sixoscillation parameters to an accuracy of better than 1\%. Neutrino burst from atypical core-collapse supernova at 10 kpc would lead to ~5000inverse-beta-decay events and ~2000 all-flavor neutrino-proton elasticscattering events in JUNO. Detection of DSNB would provide valuable informationon the cosmic star-formation rate and the average core-collapsed neutrinoenergy spectrum. Geo-neutrinos can be detected in JUNO with a rate of ~400events per year, significantly improving the statistics of existing geoneutrinosamples. The JUNO detector is sensitive to several exotic searches, e.g. protondecay via the $p\to K^++\bar\nu$ decay channel. The JUNO detector will providea unique facility to address many outstanding crucial questions in particle andastrophysics. It holds the great potential for further advancing our quest tounderstanding the fundamental properties of neutrinos, one of the buildingblocks of our Universe