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The diatom Paralia guyana is a tychoplanktonic microalgal species that represents one of the early diverging diatoms. P. guyana can thrive in both planktonic and benthic habitats, making a significant contribution to the occurrence of red tide events. Although a dozen diatom genomes have been sequenced, the identity of the early diverging diatoms remains elusive. The understanding of the evolutionary clades and mechanisms of ecological adaptation in P. guyana is limited by the absence of a high-quality genome assembly. In this study, the first high-quality genome assembly for the early diverging diatom P. guyana was established using PacBio single molecular sequencing. The assembled genome has a size of 558.85 Mb, making it the largest diatom genome on record, with a contig N50 size of 26.06 Mb. A total of 27,121 protein-coding genes were predicted in the P. guyana genome, of which 22,904 predicted genes (84.45%) were functionally annotated. This data and analysis provide innovative genomic resources for tychoplanktonic microalgal species and shed light on the evolutionary origins of diatoms. [ABSTRACT FROM AUTHOR]

Although long-read sequencing enables the generation of complete genomes for unculturable microbes, its high cost limits the widespread adoption of long-read sequencing in large-scale metagenomic studies. An alternative method is to assemble short-reads with long-range connectivity, which can be a cost-effective way to generate high-quality microbial genomes. Here, we develop Pangaea, a bioinformatic approach designed to enhance metagenome assembly using short-reads with long-range connectivity. Pangaea leverages connectivity derived from physical barcodes of linked-reads or virtual barcodes by aligning short-reads to long-reads. Pangaea utilizes a deep learning-based read binning algorithm to assemble co-barcoded reads exhibiting similar sequence contexts and abundances, thereby improving the assembly of high- and medium-abundance microbial genomes. Pangaea also leverages a multi-thresholding algorithm strategy to refine assembly for low-abundance microbes. We benchmark Pangaea on linked-reads and a combination of short- and long-reads from simulation data, mock communities and human gut metagenomes. Pangaea achieves significantly higher contig continuity as well as more near-complete metagenome-assembled genomes (NCMAGs) than the existing assemblers. Pangaea also generates three complete and circular NCMAGs on the human gut microbiomes. Here, the authors develop Pangaea, an assembler that uses short-reads with long-range connectivity to create high-quality microbial genomes affordably, showing it outperforms existing methods in generating more complete genomes from both mock and real metagenomic samples. [ABSTRACT FROM AUTHOR]

Interest and efforts to use recombinant adeno-associated viruses (AAV) as gene therapy delivery tools to treat disease have grown exponentially. However, gaps in understanding of the pharmacokinetics/pharmacodynamics (PK/PD) and disposition of this modality exist. This position paper comes from the Novel Modalities Working Group (WG), part of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ). The pan-industry WG effort focuses on the nonclinical PK and clinical pharmacology aspects of AAV gene therapy and related bioanalytical considerations. Traditional PK concepts are generally not applicable to AAV-based therapies due to the inherent complexity of a transgene-carrying viral vector, and the multiple steps and analytes involved in cell transduction and transgene-derived protein expression. Therefore, we explain PK concepts of biodistribution of AAV-based therapies and place key terminologies related to drug exposure and PD in the proper context. Factors affecting biodistribution are presented in detail, and guidelines are provided to design nonclinical studies to enable a stage-gated progression to Phase 1 testing. The nonclinical and clinical utility of transgene DNA, mRNA, and protein analytes are discussed with bioanalytical strategies to measure these analytes. The pros and cons of qPCR vs. ddPCR technologies for DNA/RNA measurement and qualitative vs. quantitative methods for transgene-derived protein are also presented. Last, best practices and recommendations for use of clinical and nonclinical data to project human dose and response are discussed. Together, the manuscript provides a holistic framework to discuss evolving concepts of PK/PD modeling, bioanalytical technologies, and clinical dose selection in gene therapy. [ABSTRACT FROM AUTHOR]

Over the past 15 years, single-cell RNA sequencing (scRNA-seq) technology, in combination with other omics, has revealed the mechanisms of human development, tumors, and complex diseases at the genome, transcriptome, and proteome levels. However, this approach fails to directly reflect relevant spatial information, such as cell location and interactions. This limitation has been addressed with the advancement of the combination of high-resolution scRNA-seq and spatial transcriptomics (ST), which enables the identification of cell composition, intercellular and intermolecular interaction, and unravels the mechanisms of disease phenotypes. This review explores two types of ST - imaging-based ST (iST) and sequencing-based ST (sST) - and demonstrates how ST analysis can follow disease pathogenesis in a spatiotemporal manner, searching for disease-specific biomarkers. ST technology is an effective tool for resolving major biomedical and clinical problems, including tumor research, brain science, embryonic development, organ atlas construction and other pathological analysis. Looking towards the future, despite its limitations, ST has the potential to address these problems in conjunction with "dynamics, multi-omics, and resolution". Ultimately, the development of ST technology, improvement of algorithms, utilization of deep learning, and refinement of the analysis process and interpretation will determine the key to transforming ST from bench to bedside. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effect of pre-oxidation treatment at 400 °C for 1000 h on the corrosion behavior of 316L stainless steel in a high-temperature water environment. The oxide film was characterized via x-ray diffraction, x-ray photoelectron spectroscopy, scanning electron microscopy, and transmission electron microscopy. The weight gain of the pre-oxidized samples was lower than that of samples without pre-oxidation treatment. An (Ni,Fe)Fe2O4 outer layer with a spinel structure and an inner layer consisting of fine spinel oxides (FexCryNizO4) were formed on the surface of the untreated sample. In contrast, the pre-oxidized samples showed the formation of a triple layer: a hydroxide outer layer, a Cr-rich middle layer, and an Fe-rich inner layer. Moreover, the oxide film thickness was thinner than that of the sample without treatment. The results clearly indicate that the selected pre-oxidation process improved the corrosion resistance of 316L stainless steel in a high-temperature water environment. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the optimal tension for the reconstruction of the distal radioulnar ligaments (DRULs) in the treatment of the distal radioulnar joint (DRUJ) instability.Methods: A total of eight human cadaver upper extremities were used. First, the Tekscan sensor film system was used to measure the contact characteristics of the intact DRUJ. Following this, the DRULs were resected, and the measurement was repeated. The DRULs were then reconstructed according to Adams' procedure, and the contact forces under different initial tension were compared with that of the intact group to obtain the optimal tension. At that point, the contact force of the DRUJ was close to normal. The reliability of the obtained tension was verified by translational testing, which reflected the stability of the DRUJ.Results: In the neutral position, the contact force, area, and pressure inside DRUJ were 0.51 ± 0.10 N, 64.08 ± 11.58 mm2, and 8.33 ± 2.42 kPa, respectively. After the DRULs were resected, they were 0.19 ± 0.02 N, 41.75 ± 5.01 mm2, and 4.86 ± 1.06 kPa, respectively. The relationship between the tension and contact force was linear regression (Y = 0.0496x + 0.229, R2 = 0.9575, P < 0.0001). According to the equation, when the tension was 3.64-7.68 N, the contact force was close to normal. There was no statistical difference in the stability of the reconstructed DRUJ under this tension compared with the intact group (P = 0.08).Conclusion: By comparing the contact forces under different reconstruction tensions with the normal value, we obtained the optimal tension, which can provide the theoretical basis for the clinical treatment of chronic DRUJ instability. [ABSTRACT FROM AUTHOR]

Seawater electrolysis is the most promising technology for large scale hydrogen production due to the abundance and low cost of seawater in nature. However, compared with the traditional freshwater electrolysis, the issues of electrode poisoning and corrosion will occur during the seawater electrolysis process, and active and stable electrocatalysts for the hydrogen evolution reaction (HER) are thus highly desired. In this work, N, O-doped carbon foam in-situ derived from commercial melamine foam is proposed as a high-active metal-free HER electrocatalyst for seawater splitting. In acidic seawater, our catalyst shows high hydrogen generation performance with small overpotential of 161 mV at 10 mA·cm−2, a low Tafel slop of 97.5 mV·dec−1, and outstanding stability. [ABSTRACT FROM AUTHOR]

Introduction: In the reconstruction of distal radioulnar ligaments (DRULs), interference screws can be used for antegrade or retrograde fixation of grafts to the ulna. However, the biomechanics of interference screw fixation are currently unknown. This study aimed to determine the biomechanical effects of these two fixations on the distal radioulnar joint (DRUJ) in a cadaveric model and to investigate the appropriate initial tension. Materials and methods: A total of 30 human cadaver upper extremities were used, and the DRULs were reconstructed according to Adams' procedure. First, eight specimens were randomly divided into two groups: antegrade and retrograde, followed by translational testing and load testing. Then, the other eight specimens were divided into the two groups above, and the contact mechanics, including forces, areas, and pressures, were measured. Finally, to investigate the appropriate initial tension, the remaining 14 specimens were fixed with interference screws under different tensions in an antegrade way, and the translational testing was repeated as before. Results: In the neutral position, antegrade fixation exhibited less translation than retrograde fixation (7.21 ± 0.17 mm versus 10.77 ± 1.68 mm, respectively). The maximum failure load was 70.45 ± 6.20 N in antegrade fixation, while that in retrograde fixation was 35.17 ± 2.95 N (P < 0.0001). Antegrade fixation exhibited a larger increase in contact force than retrograde fixation (99.72% ± 23.88% versus 28.18% ± 10.43%) (P = 0.001). The relationship between tension and displacement was nonlinear (Y = − 1.877 ln(x) + 7.94, R2 = 0.868, P < 0.0001). Conclusions: Compared with retrograde fixation, the antegrade fixation of interference screws may be a more reliable surgical technique, as it shows a higher failure load and stability. In addition, to avoid the risk of potential arthritis caused by anterograde fixation, we propose an equation to determine the appropriate initial tension in DRUL reconstruction. [ABSTRACT FROM AUTHOR]

In our previous study, the chitosanase AqCoA and the chitooligosaccharides it produced were found to exhibit significant protective effects against fungal diseases. In this study, we enhanced the expression of AqCoA using the novel pMC-GAP that enables stable transformation of Escherichia coli, and built an integrated model based on the gene copy number, molecular chaperones, and protein production of AqCoA. In terms of gene dosage, the highest hydrolase activity was 0.32 U/ml in the strain with four copies, which was 1.78-fold higher than that of the strain with only one copy (0.18 U/ml). In addition, we found the chaperones such as PDI, ERO1, HAC1, YDJ1, SSE1, SSA4, and SSO2 improved protein expression. Furthermore, the PDI/ERO1, SSA4/SSE1, and YDJ1/SSO2 pairs synergistically increased the expression levels by 61%, 31%, and 42%, respectively. Finally, we investigated the combined effects of gene copy numbers and molecular chaperones on protein expression. The highest activity reached 2.32 U/ml in the strain with six integrated molecular chaperone expression cassettes and sixteen copies of the target gene, which was 13-fold higher than that of the control strain with only one copy (GAP-1AqCoA). Combined optimization of gene dosage and molecular chaperone combinations significantly increased the expression level of AqCoA, providing a powerful strategy to improve the expression of other heterologous proteins in P. pastoris. [ABSTRACT FROM AUTHOR]

In the era of the knowledge economy, one of the key issues is how to integrate and use intelligent information systems to collect data and make valuable predictions to support business decisions. Intelligent information systems use artificial intelligence to enhance system performance, giving the enterprise a competitive advantage. This paper uses ontology technology for user requirements analysis—defining the class, slot, and instance of the ontology—and then designs the system architecture based on that ontology. In accordance with the firm's requirements, we build a data warehouse system that is integrated with different data sources within the enterprise and that supports a web-based interface in the Internet of Things (IoT). The system also supports the standard queries, reports, summary tables, and datasets required for data mining. The proposed data mining method for manufacturing industries that use Bayesian network incorporates Bayesian theory and graphical models and can predict causal and probabilistic relationships among a set of variables. Our results bring information system functionality closer to satisfying the real-world needs of business. The proposed system can reduce production cycle times, increase the speed and accuracy with which production information is analyzed, and offer predictions that can be used for better business decisions. Data mining technology can improve the efficiency of manufacturing processes by using feedback data to tune the manufacturing parameters and improve the accuracy of yield rate predictions, giving the firm a greater competitive advantage. [ABSTRACT FROM AUTHOR]

Characterizing in vivo cellular kinetics and biodistribution of chimeric antigen receptor T (CAR-T) cells is critical for toxicity assessment, nonclinical and clinical efficacy studies. To date, the standardized assay to characterize CAR-T cell distribution, expansion, contraction, and persistence profiles is not readily available. To overcome this limitation and increase comparability among studies, we have established a universal protocol for analysis. We established a duplexing ddPCR protocol for the CAR-T transgene and reference gene to normalize the genomic DNA input prepared from mouse blood and tissues. The high-throughput gDNA extraction method enabled highly reproducible gDNA extraction while eliminating labor-intensive steps. The investigational CAR-T cells were intravenously injected into immunodeficient mice bearing human colorectal cancer xenografts. The blood and tissue samples were collected to measure the cellular kinetics by ddPCR and flow cytometry. The standard curves were linear throughout the calibration range with acceptable intra- and inter-day precision and accuracy. The gDNA recovery study performed by spiking in the exo-gene plasmid DNA or CAR-T cells revealed that the recovery ranged from 60 to 100% in blood and tissue homogenates. The use of both units of copy/μg gDNA and copy/μL blood met the current regulatory requirement and allowed for a systematic understanding of CAR-T cell expansion and a direct comparison with the flow cytometry data. A standardized ddPCR assay, including automated gDNA extraction procedures, has been established for evaluating cellular kinetics and biodistribution in CAR-T cell therapies. [ABSTRACT FROM AUTHOR]

Current knowledge about the evolutionary history of donkeys is still incomplete due to the lack of archeological and whole-genome diversity data. To fill this gap, we have de novo assembled a chromosome-level reference genome of one male Dezhou donkey and analyzed the genomes of 126 domestic donkeys and seven wild asses. Population genomics analyses indicate that donkeys were domesticated in Africa and conclusively show reduced levels of Y chromosome variability and discordant paternal and maternal histories, possibly reflecting the consequences of reproductive management. We also investigate the genetic basis of coat color. While wild asses show diluted gray pigmentation (Dun phenotype), domestic donkeys display non-diluted black or chestnut coat colors (non-Dun) that were probably established during domestication. Here, we show that the non-Dun phenotype is caused by a 1 bp deletion downstream of the TBX3 gene, which decreases the expression of this gene and its inhibitory effect on pigment deposition. A new donkey reference genome and comparisons with wild asses yields insights into the evolutionary history of donkey domestication and identifies a genetic variant that results in the non-Dun coat colours of domestic donkeys. [ABSTRACT FROM AUTHOR]

Transparent conducting amorphous p-type CuFeO (CFO) thin film was prepared by radio-frequency (RF) magnetron sputtering method at room temperature using polycrystalline CuFeO target. Amorphous structure of as-deposited film was confirmed by XRD. XPS analysis convinced that the chemical state of Cu and Fe in the film, and the chemical composition of the thin films is close to the stoichiometry of CuFeO. Surface morphology of the film was analysed by SEM studies. p-type nature and concentration of carriers was investigated by Hall effect measurement. The p-n heterojunction in the structure of Al/n-Si/p-CuFeO/Al showed good rectifying behaviour with a forward and reverse currents ratio of 555 at 2 V. The turn-on voltage and reverse leakage current values were found to be 0.9 V and 4 μA at −2 V. Further, the conduction mechanism of forward bias voltage was controlled by thermionic emission (TE) and trap-space charge limited current (TCLC) mechanisms. [ABSTRACT FROM AUTHOR]

SOAPsnv is the software used for identifying the single nucleotide variation in cancer genes. However, its performance is yet to match the massive amount of data to be processed. Experiments reveal that the main performance bottleneck of SOAPsnv software is the pileup algorithm. The original pileup algorithm's I/O process is time-consuming and inefficient to read input files. Moreover, the scalability of the pileup algorithm is also poor. Therefore, we designed a new algorithm, named BamPileup, aiming to improve the performance of sequential read, and the new pileup algorithm implemented a parallel read mode based on index. Using this method, each thread can directly read the data start from a specific position. The results of experiments on the Tianhe-2 supercomputer show that, when reading data in a multi-threaded parallel I/O way, the processing time of algorithm is reduced to 3.9 s and the application program can achieve a speedup up to 100×. Moreover, the scalability of the new algorithm is also satisfying. [ABSTRACT FROM AUTHOR]

Domestic pigs have evolved genetic adaptations to their local environmental conditions, such as cold and hot climates. We sequenced the genomes of 69 pigs from 15 geographically divergent locations in China and detected 41 million variants, of which 21 million were absent from the dbSNP database. In a genome-wide scan, we identified a set of loci that likely have a role in regional adaptations to high- and low-latitude environments within China. Intriguingly, we found an exceptionally large (14-Mb) region with a low recombination rate on the X chromosome that appears to have two distinct haplotypes in the high- and low-latitude populations, possibly underlying their adaptation to cold and hot environments, respectively. Surprisingly, the adaptive sweep in the high-latitude regions has acted on DNA that might have been introgressed from an extinct Sus species. Our findings provide new insights into the evolutionary history of pigs and the role of introgression in adaptation. [ABSTRACT FROM AUTHOR]

Two calcium carbonate crystal polymorphs, aragonite and calcite, are the main inorganic components of mollusk shells. Some fossil evidences suggest that aragonite shell is more ancient than calcite shell for the Bivalvia. But, the molecular biology evidence for the above deduction is absent. In this study, we searched for homologs of bivalve aragonite-related and calcite-related shell proteins in the oyster genome, and found that no homologs of calcite-related shell protein but some homologs of aragonite-related shell proteins in the oyster genome. We explained the results as the new evidence to support that aragonite shells are more ancient than calcite shells in bivalves combined the published biogeological and seawater chemistry data. [ABSTRACT FROM AUTHOR]

Single phase delafossite CuFeO thin films were synthesized by a simple sol-gel method. The influence of polyethylene glycol (PEG) on the morphology and optoelectronic properties of the films was studied by addition of 1.0 g PEG in 10 ml precursor solution. The crystal sizes of the derived CuFeO films with and without addition of PEG were 49 nm, but the sample with addition of PEG (labeled as CFO-PEG) showed weaker c-axis orientation growth. The sample without addition of PEG (labeled as CFO) showed a compact surface without detectable pores and had a thickness around 50 nm. However, the sample CFO-PEG exhibited a porous surface with worm-like grains in nanometric scale and had a thickness around 310 nm. Enhanced absorbance in UV-vis region was observed for the sample CFO-PEG which might ascribe to both the thickness and porous surface. The optical direct bandgaps at near-UV were estimated to be ~3.0 and 3.38 eV for the sample CFO-PEG and CFO, respectively. Though the porous surface of CFO-PEG has improved the absorbance in UV-vis region, the resistivity has also been increased due to the homogeneous distribution of interspaces between the worm-like grains, which makes the incident photon to current efficiency of CFO-PEG lower than that of CFO. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease primarily affecting motor neurons. Mutations in the gene encoding TDP-43 cause some forms of the disease, and cytoplasmic TDP-43 aggregates accumulate in degenerating neurons of most individuals with ALS. Thus, strategies aimed at targeting the toxicity of cytoplasmic TDP-43 aggregates may be effective. Here, we report results from two genome-wide loss-of-function TDP-43 toxicity suppressor screens in yeast. The strongest suppressor of TDP-43 toxicity was deletion of DBR1, which encodes an RNA lariat debranching enzyme. We show that, in the absence of Dbr1 enzymatic activity, intronic lariats accumulate in the cytoplasm and likely act as decoys to sequester TDP-43, preventing it from interfering with essential cellular RNAs and RNA-binding proteins. Knockdown of Dbr1 in a human neuronal cell line or in primary rat neurons is also sufficient to rescue TDP-43 toxicity. Our findings provide insight into TDP-43-mediated cytotoxicity and suggest that decreasing Dbr1 activity could be a potential therapeutic approach for ALS. [ABSTRACT FROM AUTHOR]

The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteome of the shell. The oyster genome is highly polymorphic and rich in repetitive sequences, with some transposable elements still actively shaping variation. Transcriptome studies reveal an extensive set of genes responding to environmental stress. The expansion of genes coding for heat shock protein 70 and inhibitors of apoptosis is probably central to the oyster's adaptation to sessile life in the highly stressful intertidal zone. Our analyses also show that shell formation in molluscs is more complex than currently understood and involves extensive participation of cells and their exosomes. The oyster genome sequence fills a void in our understanding of the Lophotrochozoa. [ABSTRACT FROM AUTHOR]

Schistosomiasis is a neglected tropical disease caused by blood flukes (genus Schistosoma; schistosomes) and affecting 200 million people worldwide. No vaccines are available, and treatment relies on one drug, praziquantel. Schistosoma haematobium has come into the spotlight as a major cause of urogenital disease, as an agent linked to bladder cancer and as a predisposing factor for HIV/AIDS. The parasite is transmitted to humans from freshwater snails. Worms dwell in blood vessels and release eggs that become embedded in the bladder wall to elicit chronic immune-mediated disease and induce squamous cell carcinoma. Here we sequenced the 385-Mb genome of S. haematobium using Illumina-based technology at 74-fold coverage and compared it to sequences from related parasites. We included genome annotation based on function, gene ontology, networking and pathway mapping. This genome now provides an unprecedented resource for many fundamental research areas and shows great promise for the design of new disease interventions. [ABSTRACT FROM AUTHOR]

Parasitic diseases have a devastating, long-term impact on human health, welfare and food production worldwide. More than two billion people are infected with geohelminths, including the roundworms Ascaris (common roundworm), Necator and Ancylostoma (hookworms), and Trichuris (whipworm), mainly in developing or impoverished nations of Asia, Africa and Latin America. In humans, the diseases caused by these parasites result in about 135,000 deaths annually, with a global burden comparable with that of malaria or tuberculosis in disability-adjusted life years. Ascaris alone infects around 1.2 billion people and, in children, causes nutritional deficiency, impaired physical and cognitive development and, in severe cases, death. Ascaris also causes major production losses in pigs owing to reduced growth, failure to thrive and mortality. The Ascaris-swine model makes it possible to study the parasite, its relationship with the host, and ascariasis at the molecular level. To enable such molecular studies, we report the 273 megabase draft genome of Ascaris suum and compare it with other nematode genomes. This genome has low repeat content (4.4%) and encodes about 18,500 protein-coding genes. Notably, the A. suum secretome (about 750 molecules) is rich in peptidases linked to the penetration and degradation of host tissues, and an assemblage of molecules likely to modulate or evade host immune responses. This genome provides a comprehensive resource to the scientific community and underpins the development of new and urgently needed interventions (drugs, vaccines and diagnostic tests) against ascariasis and other nematodiases. [ABSTRACT FROM AUTHOR]

The naked mole rat (Heterocephalus glaber) is a strictly subterranean, extraordinarily long-lived eusocial mammal. Although it is the size of a mouse, its maximum lifespan exceeds 30 years, making this animal the longest-living rodent. Naked mole rats show negligible senescence, no age-related increase in mortality, and high fecundity until death. In addition to delayed ageing, they are resistant to both spontaneous cancer and experimentally induced tumorigenesis. Naked mole rats pose a challenge to the theories that link ageing, cancer and redox homeostasis. Although characterized by significant oxidative stress, the naked mole rat proteome does not show age-related susceptibility to oxidative damage or increased ubiquitination. Naked mole rats naturally reside in large colonies with a single breeding female, the 'queen', who suppresses the sexual maturity of her subordinates. They also live in full darkness, at low oxygen and high carbon dioxide concentrations, and are unable to sustain thermogenesis nor feel certain types of pain. Here we report the sequencing and analysis of the naked mole rat genome, which reveals unique genome features and molecular adaptations consistent with cancer resistance, poikilothermy, hairlessness and insensitivity to low oxygen, and altered visual function, circadian rythms and taste sensing. This information provides insights into the naked mole rat's exceptional longevity and ability to live in hostile conditions, in the dark and at low oxygen. The extreme traits of the naked mole rat, together with the reported genome and transcriptome information, offer opportunities for understanding ageing and advancing other areas of biological and biomedical research. [ABSTRACT FROM AUTHOR]

The nonhuman primates most commonly used in medical research are from the genus Macaca. To better understand the genetic differences between these animal models, we present high-quality draft genome sequences from two macaque species, the cynomolgus/crab-eating macaque and the Chinese rhesus macaque. Comparison with the previously sequenced Indian rhesus macaque reveals that all three macaques maintain abundant genetic heterogeneity, including millions of single-nucleotide substitutions and many insertions, deletions and gross chromosomal rearrangements. By assessing genetic regions with reduced variability, we identify genes in each macaque species that may have experienced positive selection. Genetic divergence patterns suggest that the cynomolgus macaque genome has been shaped by introgression after hybridization with the Chinese rhesus macaque. Macaque genes display a high degree of sequence similarity with human disease gene orthologs and drug targets. However, we identify several putatively dysfunctional genetic differences between the three macaque species, which may explain functional differences between them previously observed in clinical studies. [ABSTRACT FROM AUTHOR]

The causes of amyotrophic lateral sclerosis (ALS), a devastating human neurodegenerative disease, are poorly understood, although the protein TDP-43 has been suggested to have a critical role in disease pathogenesis. Here we show that ataxin 2 (ATXN2), a polyglutamine (polyQ) protein mutated in spinocerebellar ataxia type 2, is a potent modifier of TDP-43 toxicity in animal and cellular models. ATXN2 and TDP-43 associate in a complex that depends on RNA. In spinal cord neurons of ALS patients, ATXN2 is abnormally localized; likewise, TDP-43 shows mislocalization in spinocerebellar ataxia type 2. To assess the involvement of ATXN2 in ALS, we analysed the length of the polyQ repeat in the ATXN2 gene in 915 ALS patients. We found that intermediate-length polyQ expansions (27–33 glutamines) in ATXN2 were significantly associated with ALS. These data establish ATXN2 as a relatively common ALS susceptibility gene. Furthermore, these findings indicate that the TDP-43–ATXN2 interaction may be a promising target for therapeutic intervention in ALS and other TDP-43 proteinopathies. [ABSTRACT FROM AUTHOR]

The influence of homo-buffer layers deposited at high-temperature (HT) or low-temperature (LT) and post-annealing process on the structure and photoluminescence properties of ZnO films grown by pulsed laser deposition on Si (100) was studied by X-ray diffraction (XRD), atomic force microscope (AFM) and photoluminescence spectrum (PL). It is found that the optical property of the films can be improved greatly because the stress between the films and the substrates could be reduced by using buffer layers. By using LT buffer layer, high-quality ZnO films with only one strong ultraviolet emission (UV) can be obtained, but the post-annealing process in air will make the optical property of the film deteriorate. [ABSTRACT FROM AUTHOR]

A Correction to this paper has been published: https://doi.org/10.1208/s12248-021-00578-w [ABSTRACT FROM AUTHOR]

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21014-9 [ABSTRACT FROM AUTHOR]

The genetic landscape of clear cell renal cell carcinoma (ccRCC) had been investigated extensively but its evolution patterns remained unclear. Here we analyze the clonal architectures of 473 patients from three different populations. We find that the mutational signatures vary substantially across different populations and evolution stages. The evolution patterns of ccRCC have great inter-patient heterogeneities, with del(3p) being regarded as the common earliest event followed by three early departure points: VHL and PBRM1 mutations, del(14q) and other somatic copy number alterations (SCNAs) including amp(7), del(1p) and del(6q). We identify three prognostic subtypes of ccRCC with distinct clonal architectures and immune infiltrates: long-lived patients, enriched with VHL but depleted of BAP1 mutations, have high levels of Th17 and CD8+ T cells while short-lived patients with high burden of SCNAs have high levels of Tregs and Th2 cells, highlighting the importance of evaluating evolution patterns in the clinical management of ccRCC. Clear cell renal cell carcinoma (ccRCC) is a urogenital cancer with a well-defined genetic landscape. Here, the authors analyse the clonal architecture of ccRCC patients from three populations, and find prognostic subtypes linked to immune infiltrates and clonal architecture. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about traumatic subdural effusion (TSE) by Tsuang F. Y. and colleagues in the previous issue.

Carnivorous plants exploit animals as a nutritional source and have inspired long-standing questions about the origin and evolution of carnivory-related traits. To investigate the molecular bases of carnivory, we sequenced the genome of the heterophyllous pitcher plant Cephalotus follicularis, in which we succeeded in regulating the developmental switch between carnivorous and non-carnivorous leaves. Transcriptome comparison of the two leaf types and gene repertoire analysis identified genetic changes associated with prey attraction, capture, digestion and nutrient absorption. Analysis of digestive fluid proteins from C. follicularis and three other carnivorous plants with independent carnivorous origins revealed repeated co-options of stress-responsive protein lineages coupled with convergent amino acid substitutions to acquire digestive physiology. These results imply constraints on the available routes to evolve plant carnivory.