ALBERT

Beschreibung: Background The results of a previous study verified that umbilical cord mesenchymal stem cells (UCMSCs) have good therapeutic effects for the treatment of HBV-related acute-on-chronic liver failure (ACLF) and liver cirrhosis (LC). Nevertheless, it is still unknown whether the effects of UCMSCs are affected by recipient age. Methods Patients treated with UCMSCs who met the criteria of HBV-related ACLF and liver cirrhosis were identified in this retrospective observational study. Patients were divided into subgroups according to the World Health Organization (WHO) age criteria (

Beschreibung: Objectives To investigate the safety for clinic use and therapeutic effects of basic fibroblast growth factor (bFGF)-overexpressing human umbilical cord-derived mesenchymal stem cells (HUCMSCs) in mice with completely transected spinal cord injury (SCI). Methods Stable bFGF-overexpressing HUCMSCs clones were established by electrotransfection and then subjected to systematic safety evaluations. Then, bFGF-overexpressing and control HUCMSCs were used to treat mice with completely transected SCI by tail intravenous injection. Therapeutic outcomes were then investigated, including functional recovery of locomotion, histological structures, nerve regeneration, and recovery mechanisms. Results Stable bFGF-overexpressing HUCMSCs met the standards and safety of MSCs for clinic use. In the mouse SCI model, stable bFGF-overexpressing HUCMSCs markedly improved therapeutic outcomes such as reducing glial scar formation, improving nerve regeneration and proliferation of endogenous neural stem cells (NSCs), and increasing locomotion functional recovery of posterior limbs compared with the control HUCMSCs group. Furthermore, bFGF-overexpressing HUCMSCs promoted the proliferation and neuronal differentiation of NSCs in vitro through the PI3K-Akt-GSK-3β pathway. Conclusion bFGF-overexpressing HUCMSCs meet the requirements of clinical MSCs and improve evident therapeutic outcomes of mouse SCI treatment, which firmly supports the safety and efficacy of gene-modified MSCs for clinical application.

Beschreibung: Background Coronary artery disease (CAD) is considered as a multi-faceted chronic inflammatory disease involving reduced blood supply to the myocardium as a result of accumulating lipids in the atrial walls. Visceral adiposity with disrupted release of adipokines play a key role in its pathogenesis. Asprosin is a newly identified fasting-induced glucogenic adipokine that has been related with metabolic disorders such as type II diabetes mellitus and polycystic ovary syndrome. The preset study sought to assess circulating asprosin in context of CAD. Methods In this study, serum levels of asprosin were determined in 88 CAD patients and 88 non-CAD healthy controls. Serum IL-6, TNF-α, asprosin and adiponectin were assessed using ELISA kits. Results: Serum asprosin was found to be higher in CAD patients when compared to non-CAD subjects (7.84 ± 2.08 versus 5.02 ± 1.29 μg/mL, p 

Beschreibung: Background Metabolic stress, as negative energy balance on one hand or obesity on the other hand can lead to increased levels of free fatty acids in the plasma and follicular fluid of animals and humans. In an earlier study, we showed that increased oleic acid (OA) concentrations affected the function of cultured bovine granulosa cells (GCs). Here, we focus on genome wide effects of increased OA concentrations. Results Our data showed that 413 genes were affected, of which 197 were down- and 216 up-regulated. Specifically, the expression of FSH-regulated functional key genes, CCND2, LHCGR, INHA and CYP19A1 and 17-β-estradiol (E2) production were reduced by OA treatment, whereas the expression of the fatty acid transporter CD36 was increased and the morphology of the cells was changed due to lipid droplet accumulation. Bioinformatic analysis revealed that associated pathways of the putative upstream regulators “FSH” and “Cg (choriogonadotropin)” were inhibited and activated, respectively. Down-regulated genes are over-represented in GO terms “reproductive structure/system development”, “ovulation cycle process”, and “(positive) regulation of gonadotropin secretion”, whereas up-regulated genes are involved in “circulatory system development”, “vasculature development”, “angiogenesis” or “extracellular matrix/structure organization”. Conclusions From these data we conclude that besides inhibiting GC functionality, increased OA levels seemingly promote angiogenesis and tissue remodelling, thus suggestively initiating a premature fulliculo-luteal transition. In vivo this may lead to impeded folliculogenesis and ovulation, and cause sub-fertility.

Beschreibung: Background Left-right (LR) asymmetry is an essential feature of bilateral animals. Studies in vertebrates show that LR asymmetry formation comprises three major steps: symmetry breaking, asymmetric gene expression, and LR morphogenesis. Although much progress has been made in the first two events, mechanisms underlying asymmetric morphogenesis remain largely unknown due to the complex developmental processes deployed by vertebrate organs. Results We here addressed this question by studying Pitx gene function in the basal chordate amphioxus whose asymmetric organogenesis, unlike that in vertebrates, occurs essentially in situ and does not rely on cell migration. Pitx null mutation in amphioxus causes loss of all left-sided organs and incomplete ectopic formation of all right-sided organs on the left side, whereas Pitx partial loss-of-function leads to milder phenotypes with only some LR organs lost or ectopically formed. At the N1 to N3 stages, Pitx expression is gradually expanded from the dorsal anterior domain to surrounding regions. This leads to activation of genes like Lhx3 and/or Prop1 and Pit, which are essential for left-side organs, and downregulation of genes like Hex and/or Nkx2.1 and FoxE4, which are required for right-side organs to form ectopically on the left side. In Pitx mutants, the left-side expressed genes are not activated, while the right-side genes fail to decrease expression on the left side. In contrast, in embryos overexpressing Pitx genes, the left-side genes are induced ectopically on the right side, and the right-side genes are inhibited. Several Pitx binding sites are identified in the upstream sequences of the left-side and right-side genes which are essential for activation of the former and repression of the latter by Pitx. Conclusions Our results demonstrate that (1) Pitx is a major (although not the only) determinant of asymmetric morphogenesis in amphioxus, (2) the development of different LR organs have distinct requirements for Pitx activity, and (3) Pitx controls amphioxus LR morphogenesis probably through inducing left-side organs and inhibiting right-side organs directly. These findings show much more dependence of LR organogenesis on Pitx in amphioxus than in vertebrates. They also provide insight into the molecular developmental mechanism of some vertebrate LR organs like the lungs and atria, since they show a right-isomerism phenotype in Pitx2 knockout mice like right-sided organs in Pitx mutant amphioxus. Our results also explain why some organs like the adenohypophysis are asymmetrically located in amphioxus but symmetrically positioned in vertebrates.

Beschreibung: Background After repairing double-strand breaks (DSBs) caused by CRISPR-Cas9 cleavage, genomic damage, such as large deletions, may have pathogenic consequences. Results We show that large deletions are ubiquitous but are dependent on editing sites and cell types. Human primary T cells display more significant deletions than hematopoietic stem and progenitor cells (HSPCs), whereas we observe low levels in induced pluripotent stem cells (iPSCs). We find that the homology-directed repair (HDR) with single-stranded oligodeoxynucleotides (ssODNs) carrying short homology reduces the deletion damage by almost half, while adeno-associated virus (AAV) donors with long homology reduce large deletions by approximately 80%. In the absence of HDR, the insertion of a short double-stranded ODN by NHEJ reduces deletion indexes by about 60%. Conclusions Timely bridging of broken ends by HDR and NHEJ vastly decreases the unintended consequences of dsDNA cleavage. These strategies can be harnessed in gene editing applications to attenuate unintended outcomes.

Beschreibung: Background C. sinensis is an important economic crop with fluoride over-accumulation in its leaves, which poses a serious threat to human health due to its leaf consumption as tea. Recently, our study has indicated that cell wall proteins (CWPs) probably play a vital role in fluoride accumulation/detoxification in C. sinensis. However, there has been a lack in CWP identification and characterization up to now. This study is aimed to characterize cell wall proteome of C. sinensis leaves and to develop more CWPs related to stress response. A strategy of combined cell wall proteomics and N-glycoproteomics was employed to investigate CWPs. CWPs were extracted by sequential salt buffers, while N-glycoproteins were enriched by hydrophilic interaction chromatography method using C. sinensis leaves as a material. Afterwards all the proteins were subjected to UPLC-MS/MS analysis. Results A total of 501 CWPs and 195 CWPs were identified respectively by cell wall proteomics and N-glycoproteomics profiling with 118 CWPs in common. Notably, N-glycoproteomics is a feasible method for CWP identification, and it can enhance CWP coverage. Among identified CWPs, proteins acting on cell wall polysaccharides constitute the largest functional class, most of which might be involved in cell wall structure remodeling. The second largest functional class mainly encompass various proteases related to CWP turnover and maturation. Oxidoreductases represent the third largest functional class, most of which (especially Class III peroxidases) participate in defense response. As expected, identified CWPs are mainly related to plant cell wall formation and defense response. Conclusion This was the first large-scale investigation of CWPs in C. sinensis through cell wall proteomics and N-glycoproteomics. Our results not only provide a database for further research on CWPs, but also an insight into cell wall formation and defense response in C. sinensis.

Beschreibung: Background Finding meaningful gene-gene interaction and the main Transcription Factors (TFs) in co-expression networks is one of the most important challenges in gene expression data mining. Results Here, we developed the R package “CeTF” that integrates the Partial Correlation with Information Theory (PCIT) and Regulatory Impact Factors (RIF) algorithms applied to gene expression data from microarray, RNA-seq, or single-cell RNA-seq platforms. This approach allows identifying the transcription factors most likely to regulate a given network in different biological systems — for example, regulation of gene pathways in tumor stromal cells and tumor cells of the same tumor. This pipeline can be easily integrated into the high-throughput analysis. To demonstrate the CeTF package application, we analyzed gastric cancer RNA-seq data obtained from TCGA (The Cancer Genome Atlas) and found the HOXB3 gene as the second most relevant TFs with a high regulatory impact (TFs-HRi) regulating gene pathways in the cell cycle. Conclusion This preliminary finding shows the potential of CeTF to list master regulators of gene networks. CeTF was designed as a user-friendly tool that provides many highly automated functions without requiring the user to perform many complicated processes. It is available on Bioconductor (http://bioconductor.org/packages/CeTF) and GitHub (http://github.com/cbiagii/CeTF).

Beschreibung: Blueberry (Vaccinium ssp.) is a perennial shrub belonging to the family Ericaceae, which is highly tolerant of acid soils and heavy metal pollution. In the present study, blueberry was subjected to cadmium (Cd) stress in simulated pot culture. The transcriptomics and rhizosphere fungal diversity of blueberry were analyzed, and the iron (Fe), manganese (Mn), copper (Cu), zinc (Zn) and cadmium (Cd) content of blueberry tissues, soil and DGT was determined. A correlation analysis was also performed. A total of 84 374 annotated genes were identified in the root, stem, leaf and fruit tissue of blueberry, of which 3370 were DEGs, and in stem tissue, of which 2521 were DEGs. The annotation data showed that these DEGs were mainly concentrated in a series of metabolic pathways related to signal transduction, defense and the plant–pathogen response. Blueberry transferred excess Cd from the root to the stem for storage, and the highest levels of Cd were found in stem tissue, consistent with the results of transcriptome analysis, while the lowest Cd concentration occurred in the fruit, Cd also inhibited the absorption of other metal elements by blueberry. A series of genes related to Cd regulation were screened by analyzing the correlation between heavy metal content and transcriptome results. The roots of blueberry rely on mycorrhiza to absorb nutrients from the soil. The presence of Cd has a significant effect on the microbial community composition of the blueberry rhizosphere. The fungal family Coniochaetaceae, which is extremely extremelytolerant, has gradually become the dominant population. The results of this study increase our understanding of the plant regulation mechanism for heavy metals, and suggest potential methods of soil remediation using blueberry.

Beschreibung: Several bioinformatic tools have been developed for genome-wide identification of orthologous and paralogous genes. However, no corresponding tool allows the detection of exon homology relationships. Here, we present ExOrthist, a fully reproducible Nextflow-based software enabling inference of exon homologs and orthogroups, visualization of evolution of exon-intron structures, and assessment of conservation of alternative splicing patterns. ExOrthist evaluates exon sequence conservation and considers the surrounding exon-intron context to derive genome-wide multi-species exon homologies at any evolutionary distance. We demonstrate its use in different evolutionary scenarios: whole genome duplication in frogs and convergence of Nova-regulated splicing networks (https://github.com/biocorecrg/ExOrthist).

Beschreibung: Objective To compare an objective with a subjective numeracy assessment for association with self-reported health status, where numeracy refers to “the degree to which individuals have the capacity to access, process, interpret, communicate, and act on numerical, quantitative, graphical, biostatistical, and probabilistic health information needed to make effective health decisions” Results We completed a secondary analysis of two population-based surveys, the Empire State Poll (n = 763) and the Program for the International Assessment of Adult Competencies (PIAAC; n = 2609). The first survey assessed numeracy with a 3-item subjective instrument. The second assessed numeracy with more than 20 math problems. Both used the same measure for self-reported health status. Lower numeracy, whether subjectively or objectively assessed, was associated with worse self-reported health, even after controlling for education and other sociodemographic confounders. The odds ratios for the association were very similar (0.91 and 0.90 respectively). A lengthy objective numeracy assessment and a brief self-report assessment had similar associations with health status. A brief self-report measure of numeracy has similar properties to a lengthy objective assessment and is likely to be more feasible to use to screen patients in practice.

Beschreibung: Background Sorghum yields in sub-Saharan Africa (SSA) are greatly reduced by parasitic plants of the genus Striga (witchweed). Vast global sorghum genetic diversity collections, as well as the availability of modern sequencing technologies, can be potentially harnessed to effectively manage the parasite. Results We used laboratory assays – rhizotrons to screen a global sorghum diversity panel to identify new sources of resistance to Striga; determine mechanisms of resistance, and elucidate genetic loci underlying the resistance using genome-wide association studies (GWAS). New Striga resistant sorghum determined by the number, size and biomass of parasite attachments were identified. Resistance was by; i) mechanical barriers that blocked parasite entry, ii) elicitation of a hypersensitive reaction that interfered with parasite development, and iii) the inability of the parasite to develop vascular connections with hosts. Resistance genes underpinning the resistance corresponded with the resistance mechanisms and included pleiotropic drug resistance proteins that transport resistance molecules; xylanase inhibitors involved in cell wall fortification and hormonal regulators of resistance response, Ethylene Response Factors. Conclusions Our findings are of fundamental importance to developing durable and broad-spectrum resistance against Striga and have far-reaching applications in many SSA countries where Striga threatens the livelihoods of millions of smallholder farmers that rely on sorghum as a food staple.

Beschreibung: Background Forest carbon models are recognized as suitable tools for the reporting and verification of forest carbon stock and stock change, as well as for evaluating the forest management options to enhance the carbon sink provided by sustainable forestry. However, given their increased complexity and data availability, different models may simulate different estimates. Here, we compare carbon estimates for Romanian forests as simulated by two models (CBM and EFISCEN) that are often used for evaluating the mitigation options given the forest-management choices. Results The models, calibrated and parameterized with identical or harmonized data, derived from two successive national forest inventories, produced similar estimates of carbon accumulation in tree biomass. According to CBM simulations of carbon stocks in Romanian forests, by 2060, the merchantable standing stock volume will reach an average of 377 m3 ha−1, while the carbon stock in tree biomass will reach 76.5 tC ha−1. The EFISCEN simulations produced estimates that are about 5% and 10%, respectively, lower. In addition, 10% stronger biomass sink was simulated by CBM, whereby the difference reduced over time, amounting to only 3% toward 2060. Conclusions This model comparison provided valuable insights on both the conceptual and modelling algorithms, as well as how the quality of the input data may affect calibration and projections of the stock and stock change in the living biomass pool. In our judgement, both models performed well, providing internally consistent results. Therefore, we underline the importance of the input data quality and the need for further data sampling and model improvements, while the preference for one model or the other should be based on the availability and suitability of the required data, on preferred output variables and ease of use.

Beschreibung: Background Significant investments have been made towards the implementation of mHealth applications and eRecord systems globally. However, fragmentation of these technologies remains a big challenge, often unresolved in developing countries. In particular, evidence shows little consideration for linking mHealth applications and eRecord systems. Botswana is a typical developing country in sub-Saharan Africa that has explored mHealth applications, but the solutions are not interoperable with existing eRecord systems. This paper describes Botswana’s eRecord systems interoperability landscape and provides guidance for linking mHealth applications to eRecord systems, both for Botswana and for developing countries using Botswana as an exemplar. Methods A survey and interviews of health ICT workers and a review of the Botswana National eHealth Strategy were completed. Perceived interoperability benefits, opportunities and challenges were charted and analysed, and future guidance derived. Results Survey and interview responses showed the need for interoperable mHealth applications and eRecord systems within the health sector of Botswana and within the context of the National eHealth Strategy. However, the current Strategy does not address linking mHealth applications to eRecord systems. Across Botswana’s health sectors, global interoperability standards and Application Programming Interfaces are widely used, with some level of interoperability within, but not between, public and private facilities. Further, a mix of open source and commercial eRecord systems utilising relational database systems and similar data formats are supported. Challenges for linking mHealth applications and eRecord systems in Botswana were identified and categorised into themes which led to development of guidance to enhance the National eHealth Strategy. Conclusion Interoperability between mHealth applications and eRecord systems is needed and is feasible. Opportunities and challenges for linking mHealth applications to eRecord systems were identified, and future guidance stemming from this insight presented. Findings will aid Botswana, and other developing countries, in resolving the pervasive disconnect between mHealth applications and eRecord systems.

Beschreibung: Typhoons regularly drench densely populated western Pacific regions, but lightning could forecast intensity more than a day before a storm’s strength peaks.

Beschreibung: Objective The use of mice as animal models in biomedical research allows the standardization of genetic background and environmental conditions, which both affect phenotypic variability. As the use of both sexes in experiments is strongly recommended, sex-specific phenotypic variability is discussed with regard to putative consequences on the group size which is necessary for achieving valid and reproducible results. In this study, the sex-specific variability of 25 clinical chemical and hematological parameters which represent a comprehensive blood screen of laboratory mice, was analyzed in data sets which have been submitted to the Mouse Phenome Database. Results The overall analysis comprising all 25 clinical chemical and hematological parameters showed no evidence for substantial and robust general sex-specific variability. A large range of the ratio of the female and male coefficient of variation (CV) was found for every parameter among the respective strain data sets. This clearly demonstrated the appearance of unpredictable major interactions between genotype and environment regarding the sex-specific variability of the blood parameters analyzed.

Beschreibung: Objective Reported rainfall data from multiple rain gauges and its corresponding estimate from Dual-Polarization (Dual-Pol) radar is presented here. The ordered set of data pairs were collected from multiple peer reviewed publications spanning across the last decade. Data description Taken from multiple sources, the data set represents several radar sites and rain gauge sites combined for 12,734 data points. The data is relevant in various applications of hydrometeorology and engineering as well as weather forecasting. Further, the importance of accuracy in radar precipitation estimates continues to increase, necessitating the incorporation of as much data as possible.

Beschreibung: Background The abiotic stress such as soil salinization and heavy metal toxicity has posed a major threat to sustainable crop production worldwide. Previous studies revealed that halophytes were supposed to tolerate other stress including heavy metal toxicity. Though HMAD (heavy-metal-associated domain) was reported to play various important functions in Arabidopsis, little is known in Gossypium. Results A total of 169 G. hirsutum genes were identified belonging to the HMAD gene family with the number of amino acids ranged from 56 to 1011. Additionally, 84, 76 and 159 HMAD genes were identified in each G. arboreum, G. raimondii and G. barbadense, respectively. The phylogenetic tree analysis showed that the HMAD gene family were divided into five classes, and 87 orthologs of HMAD genes were identified in four Gossypium species, such as genes Gh_D08G1950 and Gh_A08G2387 of G. hirsutum are orthologs of the Gorai.004G210800.1 and Cotton_A_25987 gene in G. raimondii and G. arboreum, respectively. In addition, 15 genes were lost during evolution. Furthermore, conserved sequence analysis found the conserved catalytic center containing an anion binding (CXXC) box. The HMAD gene family showed a differential expression levels among different tissues and developmental stages in G. hirsutum with the different cis-elements for abiotic stress. Conclusions Current study provided important information about HMAD family genes under salt-stress in Gossypium genome, which would be useful to understand its putative functions in different species of cotton.

Beschreibung: Background Soybean is a globally important legume crop that provides a primary source of high-quality vegetable protein and oil. Seed protein content (SPC) is a valuable quality trait controlled by multiple genes in soybean. Results In this study, we performed quantitative trait loci (QTL) mapping, QTL-seq, and RNA sequencing (RNA-seq) to reveal the genes controlling protein content in the soybean by using the high protein content variety Nanxiadou 25. A total of 50 QTL for SPC distributed on 14 chromosomes except chromosomes 4, 12, 14, 17, 18, and 19 were identified by QTL mapping using 178 recombinant inbred lines (RILs). Among these QTL, the major QTL qSPC_20–1 and qSPC_20–2 on chromosome 20 were repeatedly detected across six tested environments, corresponding to the location of the major QTL detected using whole-genome sequencing-based QTL-seq. 329 candidate DEGs were obtained within the QTL region of qSPC_20–1 and qSPC_20–2 via gene expression profile analysis. Nine of which were associated with SPC, potentially representing candidate genes. Clone sequencing results showed that different single nucleotide polymorphisms (SNPs) and indels between high and low protein genotypes in Glyma.20G088000 and Glyma.16G066600 may be the cause of changes in this trait. Conclusions These results provide the basis for research on candidate genes and marker-assisted selection (MAS) in soybean breeding for seed protein content.

Beschreibung: Functional genomics experiments, like ChIP-Seq or ATAC-Seq, produce results that are summarized as a region set. There is no way to objectively evaluate the effectiveness of region set similarity metrics. We present Bedshift, a tool for perturbing BED files by randomly shifting, adding, and dropping regions from a reference file. The perturbed files can be used to benchmark similarity metrics, as well as for other applications. We highlight differences in behavior between metrics, such as that the Jaccard score is most sensitive to added or dropped regions, while coverage score is most sensitive to shifted regions.

Beschreibung: Background Hypertrophy is a critical process for chondrocyte differentiation and maturation during endochondral ossification, which is responsible for the formation of long bone and postnatal longitudinal growth. Increasing evidence suggests that melatonin, an indole hormone, plays a pivotal role in chondrogenesis. However, little is known about the effects of melatonin on the terminal differentiation of chondrocytes. Methods Mesenchymal stem cell (MSC)-derived chondrocytes generated by a high-density micromass culture system were induced to undergo hypertrophic differentiation. Melatonin-mediated hypertrophic differentiation was examined by reverse transcription polymerase chain reaction analysis (RT-PCR) analysis, histological staining and immunohistochemistry. Activation of the Wnt signaling pathway was evaluated by PCR array, RT-PCR, western blotting and immunofluorescence. XAV-939, a Wnt signaling pathway antagonist, was further used to determine whether the effect of melatonin on chondrocyte hypertrophic differentiation was mediated occurred by activation of Wnt signaling pathway. Results Histological staining showed melatonin increased chondrocyte cell volume and the expression of type X collagen but decreased the expression of type II collagen compared with the control group. RT-PCR showed that melatonin significantly up-regulated the gene expressions of biomarkers of hypertrophic chondrocytes, including type X collagen, alkaline phosphatase, runt-related transcription factor 2, Indian hedgehog and parathyroid hormone-related protein receptor, and melatonin down-regulated the mRNA expression of hallmarks of chondrocytes, including parathyroid hormone-related protein. PCR array showed that the effect of melatonin on chondrocyte hypertrophic differentiation was accompanied by the up-regulation of multiple target genes of the canonical Wnt signaling pathway, and this effect was blocked by XAV-939. Conclusions The current findings demonstrate that melatonin enhances the hypertrophic differentiation of MSC-derived chondrocytes through the Wnt signaling pathway. Our findings add evidence to the role of melatonin in promoting bone development and highlight the positive effects of melatonin on terminal differentiation of chondrocytes.

Beschreibung: Novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2. The virus causes an exaggerated immune response, resulting in a cytokine storm and acute respiratory distress syndrome, the leading cause of COVID-19-related mortality and morbidity. So far, no therapies have succeeded in circumventing the exacerbated immune response or cytokine storm associated with COVID-19. Mesenchymal stem cells (MSCs), through their immunomodulatory and regenerative activities, mostly mediated by their paracrine effect and extracellular vesicle production, have therapeutic potential in many autoimmune, inflammatory, and degenerative diseases. In this paper, we review clinical studies on the use of MSCs for COVID-19 treatment, including the salutary effects of MSCs on the pathophysiology of COVID-19 and the immunomodulation of the cytokine storm. Ongoing clinical trial designs, cell sources, dose and administration, and populations are summarized, and the paracrine mode of benefit is discussed. We also offer suggestions for optimizing MSC-based therapies, including genetic engineering, strategies for cell surface modification, nanotechnology applications, and combination therapies.

Beschreibung: Improving our understanding of hazards posed by future large earthquakes on the Cascadia Subduction Zone requires advancements in the methods and sampling used to date and characterize past events.

Beschreibung: Acute myeloid leukemia (AML) is a serious, life-threatening, and hardly curable hematological malignancy that affects the myeloid cell progenies and challenges patients of all ages but mostly occurs in adults. Although several therapies are available including chemotherapy, allogeneic hematopoietic stem cell transplantation (alloHSCT), and receptor-antagonist drugs, the 5-year survival of patients is quietly disappointing, less than 30%. alloHSCT is the major curative approach for AML with promising results but the treatment has severe adverse effects such as graft-versus-host disease (GVHD). Therefore, as an alternative, more efficient and less harmful immunotherapy-based approaches such as the adoptive transferring T cell therapy are in development for the treatment of AML. As such, chimeric antigen receptor (CAR) T cells are engineered T cells which have been developed in recent years as a breakthrough in cancer therapy. Interestingly, CAR T cells are effective against both solid tumors and hematological cancers such as AML. Gradually, CAR T cell therapy found its way into cancer therapy and was widely used for the treatment of hematologic malignancies with successful results particularly with somewhat better results in hematological cancer in comparison to solid tumors. The AML is generally fatal, therapy-resistant, and sometimes refractory disease with a disappointing low survival rate and weak prognosis. The 5-year survival rate for AML is only about 30%. However, the survival rate seems to be age-dependent. Novel CAR T cell therapy is a light at the end of the tunnel. The CD19 is an important target antigen in AML and lymphoma and the CAR T cells are engineered to target the CD19. In addition, a lot of research goes on the discovery of novel target antigens with therapeutic efficacy and utilizable for generating CAR T cells against various types of cancers. In recent years, many pieces of research on screening and identification of novel AML antigen targets with the goal of generation of effective anti-cancer CAR T cells have led to new therapies with strong cytotoxicity against cancerous cells and impressive clinical outcomes. Also, more recently, an improved version of CAR T cells which were called modified or smartly reprogrammed CAR T cells has been designed with less unwelcome effects, less toxicity against normal cells, more safety, more specificity, longer persistence, and proliferation capability. The purpose of this review is to discuss and explain the most recent advances in CAR T cell-based therapies targeting AML antigens and review the results of preclinical and clinical trials. Moreover, we will criticize the clinical challenges, side effects, and the different strategies for CAR T cell therapy.

Beschreibung: Background One of the major trends in angiosperm evolution was the shift from woody to herbaceous habit. However, reversals known as derived woodiness have also been reported in numerous, distantly related clades. Among theories evoked to explain the factors promoting the evolution of derived woodiness are moderate climate theory and cavitation theory. The first assumes that woody habit evolves in response to mild climate allowing for prolonged life span, which in turn leads to bigger and woodier bodies. The second sees woodiness as a result of natural selection for higher cavitation resistance in seasonally dry environments. Here, we compare climatic niches of woody and herbaceous, mostly southern African, umbellifers from the Lefebvrea clade to assess whether woody taxa in fact occur in markedly drier habitats. We also calibrate their phylogeny to estimate when derived woodiness evolved. Finally, we describe the wood anatomy of selected woody and herbaceous taxa to see if life forms are linked to any particular wood traits. Results The evolution of derived woodiness in chamaephytes and phanerophytes as well as the shifts to short-lived annual therophytes in the Lefebvrea clade took place at roughly the same time: in the Late Miocene during a trend of global climate aridification. Climatic niches of woody and herbaceous genera from the Cape Floristic Region overlap. There are only two genera with distinctly different climatic preferences: they are herbaceous and occur outside of the Cape Floristic Region. Therefore, studied herbs have an overall climatic niche wider than their woody cousins. Woody and herbaceous species do not differ in qualitative wood anatomy, which is more affected by stem architecture and, probably, reproductive strategy than by habit. Conclusions Palaeodrought was likely a stimulus for the evolution of derived woodiness in the Lefebvrea clade, supporting the cavitation theory. The concurrent evolution of short-lived annuals withering before summer exemplifies an alternative solution to the same problem of drought-induced cavitation. Changes of the life form were most likely neither spurred nor precluded by any qualitative wood traits, which in turn are more affected by internode length and probably also reproductive strategy.

Beschreibung: Research in the past decade has demonstrated that a single reference genome is not representative of a species’ diversity. MaizeGDB introduces a pan-genomic approach to hosting genomic data, leveraging the large number of diverse maize genomes and their associated datasets to quickly and efficiently connect genomes, gene models, expression, epigenome, sequence variation, structural variation, transposable elements, and diversity data across genomes so that researchers can easily track the structural and functional differences of a locus and its orthologs across maize. We believe our framework is unique and provides a template for any genomic database poised to host large-scale pan-genomic data.

Beschreibung: Background In most flowering plants, the plastid genome exhibits a quadripartite genome structure, comprising a large and a small single copy as well as two inverted repeat regions. Thousands of plastid genomes have been sequenced and submitted to public sequence repositories in recent years. The quality of sequence annotations in many of these submissions is known to be problematic, especially regarding annotations that specify the length and location of the inverted repeats: such annotations are either missing or portray the length or location of the repeats incorrectly. However, many biological investigations employ publicly available plastid genomes at face value and implicitly assume the correctness of their sequence annotations. Results We introduce , a Python package that automatically assesses the frequency of incomplete or incorrect annotations of the inverted repeats among publicly available plastid genomes. Specifically, the tool automatically retrieves plastid genomes from NCBI Nucleotide under variable search parameters, surveys them for length and location specifications of inverted repeats, and confirms any inverted repeat annotations through self-comparisons of the genome sequences. The package also includes functionality for automatic identification and removal of duplicate genome records and accounts for taxa that genuinely lack inverted repeats. A survey of the presence of inverted repeat annotations among all plastid genomes of flowering plants submitted to NCBI Nucleotide until the end of 2020 using , followed by a statistical analysis of potential associations with record metadata, highlights that release year and publication status of the genome records have a significant effect on the frequency of complete and equal-length inverted repeat annotations. Conclusion The number of plastid genomes on NCBI Nucleotide has increased dramatically in recent years, and many more genomes will likely be submitted over the next decade. enables researchers to automatically access and evaluate the inverted repeats of these plastid genomes as well as their sequence annotations and, thus, contributes to increasing the reliability of publicly available plastid genomes. The software is freely available via the Python package index at http://pypi.python.org/pypi/airpg.

Beschreibung: Objectives Peer support is rapidly being introduced into mental health services internationally, yet peer support interventions are often poorly described, limiting the usefulness of research in informing policy and practice. This paper reports the development of a peer support intervention that aims to improve outcomes of discharge from inpatient to community mental health care. People with experiential knowledge of using mental health services—peer workers and service user researchers—were involved in all stages of developing the intervention: generating intervention components; producing the intervention handbook; piloting the intervention. Results Systematic review and expert panels, including our Lived Experience Advisory Panel, identified 66 candidate intervention components in five domains: Recruitment and Role Description of Peer Workers; Training for Peer Workers; Delivery of Peer Support; Supervision and Support for Peer Workers; Organisation and Team. A series of Local Advisory Groups were used to prioritise components and explore implementation issues using consensus methods, refining an intervention blueprint. A peer support handbook and peer worker training programme were produced by the study team and piloted in two study sites. Feedback workshops were held with peer workers and their supervisors to produce a final handbook and training programme. The ENRICH trial is registered with the ISRCTN clinical trial register, number ISRCTN 10043328, and was overseen by an independent steering committee and a data monitoring committee.

Beschreibung: A decade of study into the Virginia earthquake that damaged D.C. and reverberated up and down the Atlantic coast in 2011 has shed light on rare, but risk-laden, seismicity in eastern North America.

Beschreibung: Background As effects of global climate change intensify, the interaction of biotic and abiotic stresses increasingly threatens current agricultural practices. The secondary cell wall is a vanguard of resistance to these stresses. Fusarium thapsinum (Fusarium stalk rot) and Macrophomina phaseolina (charcoal rot) cause internal damage to the stalks of the drought tolerant C4 grass, sorghum (Sorghum bicolor (L.) Moench), resulting in reduced transpiration, reduced photosynthesis, and increased lodging, severely reducing yields. Drought can magnify these losses. Two null alleles in monolignol biosynthesis of sorghum (brown midrib 6-ref, bmr6-ref; cinnamyl alcohol dehydrogenase, CAD; and bmr12-ref; caffeic acid O-methyltransferase, COMT) were used to investigate the interaction of water limitation with F. thapsinum or M. phaseolina infection. Results The bmr12 plants inoculated with either of these pathogens had increased levels of salicylic acid (SA) and jasmonic acid (JA) across both watering conditions and significantly reduced lesion sizes under water limitation compared to adequate watering, which suggested that drought may prime induction of pathogen resistance. RNA-Seq analysis revealed coexpressed genes associated with pathogen infection. The defense response included phytohormone signal transduction pathways, primary and secondary cell wall biosynthetic genes, and genes encoding components of the spliceosome and proteasome. Conclusion Alterations in the composition of the secondary cell wall affect immunity by influencing phenolic composition and phytohormone signaling, leading to the action of defense pathways. Some of these pathways appear to be activated or enhanced by drought. Secondary metabolite biosynthesis and modification in SA and JA signal transduction may be involved in priming a stronger defense response in water-limited bmr12 plants.

Beschreibung: Background Retinol binding protein 4 (RBP4) has been proposed to play a role in the pathophysiology of coronary artery disease (CAD), but previous findings on the association of RBP4 levels with CAD are inconsistent. Methods A meta-analysis based on observational studies was conducted to evaluate the association between circulating RBP4 levels and CAD. Databases including PubMed, Web of Science, Embase, Google Scholar and ClinicalTrials.gov database were searched for eligible studies published up to 12 July 2021. Standard mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using the inverse variance heterogeneity (IVhet) and random-effects model for data with moderate and high heterogeneity (I2 〉 30%) and data with low heterogeneity were analysed using a fixed-effects model (I2 ≤ 30%). Moreover, a bias-adjusted quality-effects model was generated, and the prediction interval was also calculated under the random-effects model. Results Two nested case-control studies, one cohort study and twelve case–control studies with a total of 7111 participants were included. Circulating RBP4 levels in patients with CAD were comparable to those in the controls under the IVhet model (SMD: 0.25, 95% CI: − 0.29-0.79, I2: 96.00%). The quality-effects model produced consistent results. However, the association turned to be significant under the random-effect model (SMD: 0.46, 95% CI: 0.17–0.75, I2: 96.00%), whereas the 95% predictive interval (PI) included null values (95% PI: − 0.82-1.74). Subgroup analyses illustrated a positive relationship between CAD and RBP4 levels in patients with complications (SMD: 1.34, 95% CI: 0.38–2.29, I2: 96.00%). The meta-regression analysis revealed that the mean BMI of patients (P = 0.03) and complication status (P = 0.01) influenced the variation in SMD. Conclusions There was low-quality evidence that patients with CAD exhibited similar circulating RBP4 levels compared with controls, and high inter-study heterogeneity was also observed. Thus, RBP4 might not be a potential risk factor for CAD. Comparisons among different subtypes of RBP4 with larger sample size are needed in the future.

Beschreibung: Background To understand the mechanism of glucosinolates (GSs) accumulation in the specific organs, combined analysis of physiological change and transcriptome sequencing were applied in the current study. Taking Chinese kale as material, seeds and silique walls were divided into different stages based on the development of the embryo in seeds and then subjected to GS analysis and transcriptome sequencing. Results The main GS in seeds of Chinese kale were glucoiberin and gluconapin and their content changed with the development of the seed. During the transition of the embryo from torpedo- to the early cotyledonary-embryo stage, the accumulation of GS in the seed was accompanied by the salient decline of GS in the corresponding silique wall. Thus, the seed and corresponding silique wall at these two stages were subjected to transcriptomic sequencing analysis. 135 genes related to GS metabolism were identified, of which 24 genes were transcription factors, 81 genes were related to biosynthetic pathway, 25 genes encoded catabolic enzymes, and 5 genes matched with transporters. The expression of GS biosynthetic genes was detected both in seeds and silique walls. The high expression of FMOGS-OX and AOP2, which is related to the production of gluconapin by side modification, was noted in seeds at both stages. Interestingly, the expression of GS biosynthetic genes was higher in the silique wall compared with that in the seed albeit lower content of GS existed in the silique wall than in the seed. Combined with the higher expression of transporter genes GTRs in silique walls than in seeds, it was proposed that the transportation of GS from the silique wall to the seed is an important source for seed GS accumulation. In addition, genes related to GS degradation expressed abundantly in the seed at the early cotyledonary-embryo stage indicating its potential role in balancing seed GS content. Conclusions Two stages including the torpedo-embryo and the early cotyledonary-embryo stage were identified as crucial in GS accumulation during seed development. Moreover, we confirmed the transportation of GS from the silique wall to the seed and proposed possible sidechain modification of GS biosynthesis may exist during seed formation.

Beschreibung: Background Drug–drug interactions (DDIs) refer to processes triggered by the administration of two or more drugs leading to side effects beyond those observed when drugs are administered by themselves. Due to the massive number of possible drug pairs, it is nearly impossible to experimentally test all combinations and discover previously unobserved side effects. Therefore, machine learning based methods are being used to address this issue. Methods We propose a Siamese self-attention multi-modal neural network for DDI prediction that integrates multiple drug similarity measures that have been derived from a comparison of drug characteristics including drug targets, pathways and gene expression profiles. Results Our proposed DDI prediction model provides multiple advantages: (1) It is trained end-to-end, overcoming limitations of models composed of multiple separate steps, (2) it offers model explainability via an Attention mechanism for identifying salient input features and (3) it achieves similar or better prediction performance (AUPR scores ranging from 0.77 to 0.92) compared to state-of-the-art DDI models when tested on various benchmark datasets. Novel DDI predictions are further validated using independent data resources. Conclusions We find that a Siamese multi-modal neural network is able to accurately predict DDIs and that an Attention mechanism, typically used in the Natural Language Processing domain, can be beneficially applied to aid in DDI model explainability.

Beschreibung: Background Modulating the microbiota is a leading-edge strategy for the restoration and maintenance of a healthy, balanced environment. The use of health-promoting bacteria has demonstrated some potential benefits as an alternative for skin microbiota intervention. Here, we investigate the manipulation of mice skin microbiota using B. subtilis incorporated into a supportive Pluronic F-127 hydrogel formulation. The formula plays an important role in delivering the bacteria to the desired action site. Results The B. subtilis challenge induced a shift in the composition and abundance of the skin microbiota. Containment of B. subtilis in the Pluronic F-127 hydrogel accelerated bacterial modulation compared with free B. subtilis. The abundance of both Staphylococcus and Corynebacterium spp. was altered as a result of the live bacterial intervention: the abundance of Corynebacterium increased while that of Staphylococcus decreased. Four days after last application of the B. subtilis formulation, B. subtilis counts returned to its initial level. Conclusions B. subtilis intervention can induce a shift in the skin microbiota, influencing the abundance of commensal, beneficial, and pathogenic bacteria. Containment of B. subtilis in Pluronic hydrogel accelerates the microbial alteration, probably by facilitating bacterial attachment and supporting continuous growth. Our results reveal the ability of B. subtilis in Pluronic to modulate the skin microbiota composition, suggesting that the formulation holds therapeutic potential for skin disease treatment.

Beschreibung: Background Mycotoxins are among the environmental stressors whose oxidative action is currently widely studied. The aim of this paper was to investigate the response of seedling leaves to zearalenone (ZEA) applied to the leaves (directly) and to the grains (indirectly) in tolerant and sensitive wheat cultivars. Results Biochemical analyses of antioxidant activity were performed for chloroplasts and showed a similar decrease in this activity irrespective of plant sensitivity and the way of ZEA application. On the other hand, higher amounts of superoxide radical (microscopic observations) were generated in the leaves of plants grown from the grains incubated in ZEA solution and in the sensitive cultivar. Electron paramagnetic resonance (EPR) studies showed that upon ZEA treatment greater numbers of Mn - aqua complexes were formed in the leaves of the tolerant wheat cultivar than in those of the sensitive one, whereas the degradation of Fe-protein complexes occurred independently of the cultivar sensitivity. Conclusion The changes in the quantity of stable, organic radicals formed by stabilizing reactive oxygen species on biochemical macromolecules, indicated greater potential for their generation in leaf tissues subjected to foliar ZEA treatment. This suggested an important role of these radical species in protective mechanisms mainly against direct toxin action. The way the defense mechanisms were activated depended on the method of the toxin application.

Beschreibung: Background Genome-wide data are invaluable to characterize differentiation and adaptation of natural populations. Reduced representation sequencing (RRS) subsamples a genome repeatedly across many individuals. However, RRS requires careful optimization and fine-tuning to deliver high marker density while being cost-efficient. The number of genomic fragments created through restriction enzyme digestion and the sequencing library setup must match to achieve sufficient sequencing coverage per locus. Here, we present a workflow based on published information and computational and experimental procedures to investigate and streamline the applicability of RRS. Results In an iterative process genome size estimates, restriction enzymes and size selection windows were tested and scaled in six classes of Antarctic animals (Ostracoda, Malacostraca, Bivalvia, Asteroidea, Actinopterygii, Aves). Achieving high marker density would be expensive in amphipods, the malacostracan target taxon, due to the large genome size. We propose alternative approaches such as mitogenome or target capture sequencing for this group. Pilot libraries were sequenced for all other target taxa. Ostracods, bivalves, sea stars, and fish showed overall good coverage and marker numbers for downstream population genomic analyses. In contrast, the bird test library produced low coverage and few polymorphic loci, likely due to degraded DNA. Conclusions Prior testing and optimization are important to identify which groups are amenable for RRS and where alternative methods may currently offer better cost-benefit ratios. The steps outlined here are easy to follow for other non-model taxa with little genomic resources, thus stimulating efficient resource use for the many pressing research questions in molecular ecology.

Beschreibung: Background Panicle is a harvesting organ of rice, and its morphology and development are closely associated with grain yield. The current study was carried on a mutant screened through an EMS (ethyl-methane sulphonate) mutagenized population of a Japonica cultivar Kitaake (WT). Results A mutant, named as asp-lsl (aberrant spikelet-long sterile lemma), showed a significant decrease in plant height, number of tillers, thousand-grains weight, seed setting rate, spikelet length, kernel length and effective number of grains per panicle as compared to WT. Asp-lsl showed a pleiotropic phenotype coupled with the obvious presence of a long sterile lemma. Cross-sections of lemma showed an increase in the cell volume rather than the number of cells. Genetic segregation analysis revealed its phenotypic trait is controlled by a single recessive nuclear gene. Primary and fine mapping indicated that candidate gene controlling the phenotype of asp-lsl was located in an interval of 212 kb on the short arm of chromosome 8 between RM22445 and RM22453. Further sequencing and indels markers analysis revealed LOC_Os08g06480 harbors a single base substitution (G→A), resulting in a change of 521st amino acid(Gly→Glu. The homology comparison and phylogenetic tree analysis revealed mutation was occurred in a highly conserved domain and had a high degree of similarity in Arabidopsis, corn, and sorghum. The CRISPR/Cas9 mutant line of ASP-LSL produced a similar phenotype as that of asp-lsl. Subcellular localization of ASP-LSL revealed that its protein is localized in the nucleus. Relative expression analysis revealed ASP-LSL was preferentially expressed in panicle, stem, and leaves. The endogenous contents of GA, CTK, and IAA were found significantly decreased in asp-lsl as compared to WT. Conclusions Current study presents the novel phenotype of asp-lsl and also validate the previously reported function of OsREL2 (ROMOSA ENHANCER LOCI2), / ASP1(ABERRANT SPIKELET AND PANICLE 1).

Beschreibung: Background Recent advances in sequencing technologies have driven studies identifying the microbiome as a key regulator of overall health and disease in the host. Both 16S amplicon and whole genome shotgun sequencing technologies are currently being used to investigate this relationship, however, the choice of sequencing technology often depends on the nature and experimental design of the study. In principle, the outputs rendered by analysis pipelines are heavily influenced by the data used as input; it is then important to consider that the genomic features produced by different sequencing technologies may emphasize different results. Results In this work, we use public 16S amplicon and whole genome shotgun sequencing (WGS) data from the same dogs to investigate the relationship between sequencing technology and the captured gut metagenomic landscape in dogs. In our analyses, we compare the taxonomic resolution at the species and phyla levels and benchmark 12 classification algorithms in their ability to accurately identify host phenotype using only taxonomic relative abundance information from 16S and WGS datasets with identical study designs. Our best performing model, a random forest trained by the WGS dataset, identified a species (Bacteroides coprocola) that predominantly contributes to the abundance of leuB, a gene involved in branched chain amino acid biosynthesis; a risk factor for glucose intolerance, insulin resistance, and type 2 diabetes. This trend was not conserved when we trained the model using 16S sequencing profiles from the same dogs. Conclusions Our results indicate that WGS sequencing of dog microbiomes detects a greater taxonomic diversity than 16S sequencing of the same dogs at the species level and with respect to four gut-enriched phyla levels. This difference in detection does not significantly impact the performance metrics of machine learning algorithms after down-sampling. Although the important features extracted from our best performing model are not conserved between the two technologies, the important features extracted from either instance indicate the utility of machine learning algorithms in identifying biologically meaningful relationships between the host and microbiome community members. In conclusion, this work provides the first systematic machine learning comparison of dog 16S and WGS microbiomes derived from identical study designs.

Beschreibung: Background Aberrant expression of Aldo-Keto reductase family 1 member B10 (AKR1B10) was associated with tumor size and metastasis of breast cancer in our published preliminary studies. However, little is known about the detailed function and underlying molecular mechanism of AKR1B10 in the pathological process of breast cancer. Methods The relationship between elevated AKR1B10 expression and the overall survival and disease-free survival of breast cancer patients was analyzed by Kaplan–Meier Plotter database. Breast cancer cell lines overexpressing AKR1B10 (MCF-7/AKR1B10) and breast cancer cell lines with knockdown of AKR1B10 (BT-20/shAKR1B10) were constructed to analyze the impact of AKR1B10 expression on cell proliferation and migration of breast cancer. The expression levels of AKR1B10 were detected and compared in the breast cancer cell lines and tissues by RT-qPCR, western blot and immunohistochemistry. The proliferation of breast cancer cells was monitored by CCK8 cell proliferation assay, and the migration and invasion of breast cancer cells was observed by cell scratch test and transwell assay. The proliferation- and EMT-related proteins including cyclinD1, c-myc, Survivin, Twist, SNAI1, SLUG, ZEB1, E-cadherin, PI3K, p-PI3K, AKT, p-AKT, IKBα, p-IKBα, NF-κB p65, p-NF-κB p65 were detected by western blot in breast cancer cells. MCF-7/AKR1B10 cells were treated with LY294002, a PI3K inhibitor, to consider the impact of AKR1B10 overexpression on the PI3K/AKT/NF-κB signal cascade and the presence of NF-κB p65 in nuclear. In vivo tumor xenograft experiments were used to observe the role of AKR1B10 in breast cancer growth in mice. Results AKR1B10 expression was significantly greater in breast cancer tissue compared to paired non-cancerous tissue. The expression of AKR1B10 positively correlated with lymph node metastasis, tumor size, Ki67 expression, and p53 expression, but inversely correlated with overall and disease-free survival rates. Gene Ontology analysis showed that AKR1B10 activity contributes to cell proliferation. Overexpression of AKR1B10 facilitated the proliferation of MCF-7 cells, and induced the migration and invasion of MCF-7 cells in vitro in association with induction of epithelial-mesenchymal transition (EMT). Conversely, knockdown of AKR1B10 inhibited these effects in BT-20 cells. Mechanistically, AKR1B10 activated PI3K, AKT, and NF-κB p65, and induced nuclear translocation of NF-κB p65, and expression of proliferation-related proteins including c-myc, cyclinD1, Survivin, and EMT-related proteins including ZEB1, SLUG, Twist, but downregulated E-cadherin expression in MCF-7 cells. AKR1B10 silencing reduced the phosphorylation of PI3K, AKT, and NF-κB p65, the nuclear translocation of NF-κB p65, and the expression of proliferation- and migration-related proteins in BT-20 cells. LY294002, a PI3K inhibitor, attenuated the phosphorylation of PI3K, AKT, and NF-κB p65, and the nuclear translocation of NF-κB p65. In vivo tumor xenograft experiments confirmed that AKR1B10 promoted breast cancer growth in mice. Conclusions AKR1B10 promotes the proliferation, migration and invasion of breast cancer cells via the PI3K/AKT/NF-κB signaling pathway and represents a novel prognostic indicator as well as a potential therapeutic target in breast cancer.

Beschreibung: Background To enhance teleconsultation management, demands can be classified into different patterns, and the service of each pattern demand can be improved. Methods For the effective teleconsultation classification, a novel ensemble hierarchical clustering method is proposed in this study. In the proposed method, individual clustering results are first obtained by different hierarchical clustering methods, and then ensembled by one-hot encoding, the calculation and division of cosine similarity, and network graph representation. In the built network graph about the high cosine similarity, the connected demand series can be categorized into one pattern. For verification, 43 teleconsultation demand series are used as sample data, and the efficiency and quality of teleconsultation services are respectively analyzed before and after the demand classification. Results The teleconsultation demands are classified into three categories, erratic, lumpy, and slow. Under the fixed strategies, the service analysis after demand classification reveals the deficiencies of teleconsultation services, but analysis before demand classification can’t. Conclusion The proposed ensemble hierarchical clustering method can effectively category teleconsultation demands, and the effective demand categorization can enhance teleconsultation management.

Beschreibung: A 4D back-projection method revealed that aftershocks of the 2015 earthquake beneath the Ogasawara (Bonin) Islands occurred as deep as about 750 kilometers.

Beschreibung: Background The plant body in duckweed species has undergone reduction and simplification from the ancient Spirodela species towards more derived Wolffia species. Among the five duckweed genera, Wolffia members are rootless and represent the smallest and most reduced species. A better understanding of Wolffia frond architecture is necessary to fully explore duckweed evolution. Results We conducted a comprehensive study of the morphology and anatomy of Wolffia globosa, the only Wolffia species in China. We first used X-ray microtomography imaging to reveal the three-dimensional and internal structure of the W. globosa frond. This showed that new fronds rapidly budded from the hollow reproductive pocket of the mother fronds and that several generations at various developmental stages could coexist in a single W. globosa frond. Using light microscopy, we observed that the meristem area of the W. globosa frond was located at the base of the reproductive pocket and composed of undifferentiated cells that continued to produce new buds. A single epidermal layer surrounded the W. globosa frond, and the mesophyll cells varied from small and dense palisade-like parenchyma cells to large, vacuolated cells from the ventral to the dorsal part. Furthermore, W. globosa fronds contained all the same organelles as other angiosperms; the most prominent organelles were chloroplasts with abundant starch grains. Conclusions Our study revealed that the reproductive strategy of W. globosa plants enables the rapid accumulation of biomass and the wide distribution of this species in various habitats. The reduced body plan and size of Wolffia are consistent with our observation that relatively few cell types are present in these plants. We also propose that W. globosa plants are not only suitable for the study of structural reduction in higher plants, but also an ideal system to explore fundamental developmental processes of higher plants that cannot be addressed using other model plants.

Beschreibung: Background Structural variants (SVs) significantly drive genome diversity and environmental adaptation for diverse species. Unlike the prevalent small SVs (〈 kilobase-scale) in higher eukaryotes, large-size SVs rarely exist in the genome, but they function as one of the key evolutionary forces for speciation and adaptation. Results In this study, we discover and characterize several megabase-scale presence-absence variations (PAVs) in the maize genome. Surprisingly, we identify a 3.2 Mb PAV fragment that shows high integrity and is present as complete presence or absence in the natural diversity panel. This PAV is embedded within the nucleolus organizer region (NOR), where the suppressed recombination is found to maintain the PAV against the evolutionary variation. Interestingly, by analyzing the sequence of this PAV, we not only reveal the domestication trace from teosinte to modern maize, but also the footprints of its origin from Tripsacum, shedding light on a previously unknown contribution from Tripsacum to the speciation of Zea species. The functional consequence of the Tripsacum segment migration is also investigated, and environmental fitness conferred by the PAV may explain the whole segment as a selection target during maize domestication and improvement. Conclusions These findings provide a novel perspective that Tripsacum contributes to Zea speciation, and also instantiate a strategy for evolutionary and functional analysis of the “fossil” structure variations during genome evolution and speciation.