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Pseudomonas syringae pv. syringae is the main causal agent of bacterial canker in sweet cherry in Chile, causing significant economic losses. Cultivars exhibit diverse susceptibility in the field and the molecular mechanisms underlying the differential responses remain unclear. RNA-seq analysis was performed to characterize the transcriptomic response in cultivars Santina and Bing (less and more susceptible to P. syringae pv. syringae, respectively) after 1 and 7 days post-inoculation (dpi) with the bacterium. Symptoms of bacterial canker became evident from the fifth day. At 1 dpi, cultivar Santina showed a faster response to infection and a larger number of differentially expressed genes (DEGs) than cultivar Bing. At 7 dpi, cultivar Bing almost doubled its DEGs, while cultivar Santina tended to the normal DEG levels. P. syringae pv. syringae infection downregulated the expressions of key genes of the photosynthesis process at 1 dpi in the less susceptible cultivar. The results suggest that the difference in susceptibility to P. syringae pv. syringae is linked to the timeliness of pathogen recognition, limiting the bacteria's dispersion through modeling its cell wall, and regulation of genes encoding photosynthesis pathway. Through this study, it has been possible to progress the knowledge of relevant factors related to the susceptibility of the two studied cherry cultivars to P. syringae pv. syringae. [ABSTRACT FROM AUTHOR]

In many crops, both pollination and biocontrol determine crop yield, whereby the relative importance of the two ecosystem services can be moderated by the landscape context. However, additive and interactive effects of pollination and biocontrol in different landscape contexts are still poorly understood. We examined both ecosystem services in South African macadamia orchards. Combining observations and experiments, we disentangled their relative additive and interactive effects on crop production with variation in orchard design and landscape context (i.e., cover of natural habitat and altitude). Insect pollination increased the nut set on average by 280% (initial nut set) and 525% (final nut set), while biocontrol provided by bats and birds reduced the insect damage on average by 40%. Pollination services increased in orchards where macadamia tree rows were positioned perpendicular to orchard edges facing natural habitat. Biocontrol services decreased with elevation. Pest damage was reduced by higher cover of natural habitat at landscape scale but increased with elevation. Pollination and biocontrol are both important ecosystem services and complementary in providing high macadamia crop yield. Smart orchard design and the retention of natural habitat can simultaneously enhance both services. Conjoint management of ecosystem services can thus enable the ecological intensification of agricultural production. [ABSTRACT FROM AUTHOR]

Liquid metal batteries have been introduced as promising option to address the needs for new energy storage technologies. Currently, batteries based on sodium and zinc are under development and a favorable option due to their high theoretical cell potential, readily abundant materials, and cost-advantages. Nevertheless, they face the problem of self-discharge, which makes it inevitable to understand fluid dynamics in the whole cell. Motivated by that, several types of fluid mechanic instabilities in Na-Zn liquid metal batteries are identified and discussed here. On the one hand they can jeopardize secure operation, but on the other hand they can also improve mixing and increase the cell efficiency. In doing so, realistic cell as well as operation parameters are included and dimensionless numbers for identifying critical conditions are presented. The phenomena with highest significance for the discussed batteries are solutal convection, swirling flow, electrocapillary Marangoni convection, and droplet formation. Still, many open research questions remain and we aim at motivating researchers to dig deeper into some of these topics to contribute to an improved cell design and performance. [ABSTRACT FROM AUTHOR]

Refugee and migrant communities from culturally and linguistically diverse backgrounds in Australia experience dependency, stigma, isolation, mental health issues, family issues and other problems associated with alcohol and other drugs. Yet, refugee and migrant communities also face major linguistic, cultural and technological barriers to health promotion about drug-related problems. The aim of this review is to identify effective techniques and approaches for health promotion that reduces the risk of problems with drugs in culturally and linguistically inclusive ways. To identify what is effective, the Medline/PubMed database was systematically searched for health promotion literature published between 2008 and 2018. Grey literature from relevant agencies was also searched. The review considered both quantitative and qualitative outcome measures, and assessed studies using the Critical Appraisal Skills Programme quality assessment tool. Three studies met inclusion criteria, with weak evaluations. The studies demonstrated effective community engagement, but do not provide conclusive evidence of what is effective drug-related health promotion. The review's findings point to an important knowledge gap. More rigorous research and evaluation are required to identify effective health promotion for reducing drug-related issues with a larger, more diverse range of refugee and migrant communities.

Abstract Background Researchers and policymakers are increasingly concerned that personalisation schemes in social and health care might be worsening social and health inequities. This has been found internationally, where better outcomes from such schemes have been found amongst those who have higher education and more household income. Method This study looks at one of the world’s largest personalisation schemes, the Australian National Disability Insurance Scheme. Using publicly available data we examine the allocation and utilisation of NDIS funds according to social gradient. Results We find that the rate at which people with disability ‘spend’ or effectively use their disability care funds follows a social gradient. That is, those in areas of higher socioeconomic disadvantage are not spending as much of their allocated budgets on care services across the year compared to people in areas of higher socioeconomic advantage. This represents a clear issue of equity in the use of public money to people with disability in Australia. Conclusion We argue that this points to the need to provide targeted supports for the use of disability care funds in areas of higher socioeconomic disadvantage. Without effective supports for fund use, the NDIS and other personalisation schemes may be positioned to worsen existing social inequalities.

Bacterial canker caused by Pseudomonas syringae pv. syringae (Pss) is responsible for substantial loss to the production of sweet cherry in Chile. To date, the molecular mechanisms of the Pss–sweet cherry interaction and the disease-related genes in the plant are poorly understood. In order to gain insight into these aspects, a transcriptomic analysis of the sweet cherry cultivar ‘Lapins’ for differentially expressed genes (DEGs) in response to Pss inoculation was conducted. Three Pss strains, A1M3, A1M197, and 11116_b1, were inoculated in young twigs, and RNA was extracted from tissue samples at the inoculation site and distal sections. RNA sequencing and transcriptomic expression analysis revealed that the three strains induced different patterns of responses in local and distal tissues. In the local tissues, A1M3 triggered a much more extensive response than the other two strains, enriching DEGs especially involved in photosynthesis. In the distal tissues, the three strains triggered a comparable extent of responses, among which 11116_b1 induced a group of DEGs involved in defense responses. Furthermore, tissues from various inoculations exhibited an enrichment of DEGs related to carbohydrate metabolism, terpene metabolism, and cell wall biogenesis. This study opened doors to future research on the Pss–sweet cherry interaction, immunity responses, and disease control.

Targeting damage to mitochondria has become an effective strategy antitumor therapies. Here, the authors report on nanoagents with upconversion nanoparticles as cores and photoacid-loaded MOFs as shells for NIR triggered Fenton reaction, acidification and calcium overload to provide synergistic mitochondrial damage.

Abstract Background Autosomal dominant osteopetrosis type II (ADO2) is a genetically and phenotypically metabolic bone disease, caused by osteoclast abnormalities. The pathways dysregulated in ADO2 could lead to the defects in osteoclast formation and function. However, the mechanism remains elusive. Materials and methods To systematically explore the molecular characterization of ADO2, we performed a multi-omics profiling from the autosomal dominant osteopetrosis type II iPSCs (ADO2-iPSCs) and healthy normal control iPSCs (NC-iPSCs) using whole genome re-sequencing, DNA methylation and N6-methyladenosine (m6A) analysis in this study. Results Totally, we detected 7,095,817 single nucleotide polymorphisms (SNPs) and 1,179,573 insertion and deletions (InDels), 1,001,943 differentially methylated regions (DMRs) and 2984 differential m6A peaks, and the comprehensive multi-omics profile was generated from the two cells. Interestingly, the ISG15 m6A level in ADO2-iPSCs is higher than NC-iPSCs by IGV software, and the differentially expressed m6A-modified genes (DEMGs) were highly enriched in the osteoclast differentiation and p53 signaling pathway, which associated with the development of osteopetrosis. In addition, combining our previously published transcriptome and proteome datasets, we found that the change in DNA methylation levels correlates inversely with some gene expression levels. Conclusion Our results indicate that the global multi-omics landscape not only provides a high-quality data resource but also reveals a dynamic pattern of gene expression, and found that the pathogenesis of ADO2 may begin early in life.

IntroductionSystemic lupus erythematosus (SLE) is a chronic autoimmune disease for which there is no cure. Effective diagnosis and precise assessment of disease exacerbation remains a major challenge.MethodsWe performed peripheral blood mononuclear cell (PBMC) proteomics of a discovery cohort, including patients with active SLE and inactive SLE, patients with rheumatoid arthritis (RA), and healthy controls (HC). Then, we performed a machine learning pipeline to identify biomarker combinations. The biomarker combinations were further validated using enzyme-linked immunosorbent assays (ELISAs) in another cohort. Single-cell RNA sequencing (scRNA-seq) data from active SLE, inactive SLE, and HC PBMC samples further elucidated the potential immune cellular sources of each of these PBMC biomarkers.ResultsScreening of the PBMC proteome identified 1023, 168, and 124 proteins that were significantly different between SLE vs. HC, SLE vs. RA, and active SLE vs. inactive SLE, respectively. The machine learning pipeline identified two biomarker combinations that accurately distinguished patients with SLE from controls and discriminated between active and inactive SLE. The validated results of ELISAs for two biomarker combinations were in line with the discovery cohort results. Among them, the six-protein combination (IFIT3, MX1, TOMM40, STAT1, STAT2, and OAS3) exhibited good performance for SLE disease diagnosis, with AUC of 0.723 and 0.815 for distinguishing SLE from HC and RA, respectively. Nine-protein combination (PHACTR2, GOT2, L-selectin, CMC4, MAP2K1, CMPK2, ECPAS, SRA1, and STAT2) showed a robust performance in assessing disease exacerbation (AUC=0.990). Further, the potential immune cellular sources of nine PBMC biomarkers, which had the consistent changes with the proteomics data, were elucidated by PBMC scRNAseq.DiscussionUnbiased proteomic quantification and experimental validation of PBMC samples from two cohorts of patients with SLE were identified as biomarker combinations for diagnosis and activity monitoring. Furthermore, the immune cell subtype origin of the biomarkers in the transcript expression level was determined using PBMC scRNAseq. These findings present valuable PBMC biomarkers associated with SLE and may reveal potential therapeutic targets.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multi-organ inflammation and defect, which is linked to many molecule mediators. Oxylipins as a class of lipid mediator have not been broadly investigated in SLE. Here, we applied targeted mass spectrometry analysis to screen the alteration of oxylipins in serum of 98 SLE patients and 106 healthy controls. The correlation of oxylipins to lupus nephritis (LN) and SLE disease activity, and the biomarkers for SLE classification, were analyzed. Among 128 oxylipins analyzed, 92 were absolutely quantified and 26 were significantly changed. They were mainly generated from the metabolism of several polyunsaturated fatty acids, including arachidonic acid (AA), linoleic acid (LA), docosahexanoic acid (DHA), eicosapentanoic acid (EPA) and dihomo-γ-linolenic acid (DGLA). Several oxylipins, especially those produced from AA, showed different abundance between patients with and without lupus nephritis (LN). The DGLA metabolic activity and DGLA generated PGE1, were significantly associated with SLE disease activity. Random forest-based machine learning identified a 5-oxylipin combination as potential biomarker for SLE classification with high accuracy. Seven individual oxylipin biomarkers were also identified with good performance in distinguishing SLE patients from healthy controls (individual AUC > 0.7). Interestingly, the biomarkers for differentiating SLE patients from healthy controls are distinct from the oxylipins differentially expressed in LN patients vs. non-LN patients. This study provides possibilities for the understanding of SLE characteristics and the development of new tools for SLE classification.

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disease with a complicated pathogenesis, and its aetiology has not been clearly unveiled. The lack of effective diagnosis and treatment methods makes it necessary to explore the molecular mechanism of SLE. We aimed to identify some critical signalling pathways and key competing endogenous RNAs (ceRNAs) underlying the molecular mechanism of SLE and to map out the systematic signalling networks by integrating the data on different kinds of RNAs. Methods Peripheral blood mononuclear cells (PBMCs) were collected from both SLE patients and healthy subjects, RNA was extracted from the PBMCs, and RNA libraries including ribosomal RNA-depleted strand-specific libraries and small RNA libraries were built for deep RNA sequencing (RNA-seq). RNA-seq yielded differential expression profiles of lncRNAs/circRNAs/miRNAs/mRNAs related to SLE. The DAVID database (v. 6.8) was employed for Gene Ontology (GO) and KEGG pathway analysis. ceRNA networks (circRNA/lncRNA-miRNA-mRNA) were constructed and visualized using Cytoscape software (v. 3.5.0). The TargetScan and miRanda databases were used to predict target relationships in ceRNA networks. qRT-PCR was used to verify our data. Results Differential expression of ceRNAs related to SLE was detected in SLE patients’ PBMCs: 644 mRNAs (384 upregulated, 260 downregulated), 326 miRNAs (223 upregulated, 103 downregulated), 221 lncRNAs (79 upregulated, 142 downregulated), and 31 circRNAs (21 upregulated, 10 downregulated). We drew ceRNA signalling networks made up of the differentially expressed mRNAs/miRNAs/lncRNAs/circRNAs mentioned above, and the hub genes included IRF5, IFNAR2, TLR7, IRAK4, STAT1, STAT2, C2, and Tyk2. These hub genes were involved in ceRNA signalling pathways, such as the IL-17 signalling pathway and type I interferon signalling pathway. Conclusions We explored the differential expression profiles of various kinds of ceRNAs and integrated signalling networks constructed by ceRNAs. Our findings offer new insights into the pathogenesis of SLE and hint at therapeutic strategies.

Abstract Background The identification of novel functional biomarkers is essential for recognizing high-risk patients, predicting recurrence, and searching for appropriate treatment. However, no prognostic biomarker has been applied for colorectal cancer (CRC) in the clinic. Methods Integrated with transcriptomic data from public databases, multi-omics examinations were conducted to search prognostic biomarkers for CRC. Moreover, the potential biological functions and regulatory mechanism of these predictive genes were also explored. Results In this study, we revealed that three mitochondrial genes were associated with the poor prognosis of CRC. Integrated analyses of transcriptome and proteome of CRC patients disclosed numerous down-regulated mitochondrial genes at both mRNA and protein levels, suggesting a vital role of mitochondria in carcinogenesis. Combined with the bioinformatics studies of transcriptomic datasets of 538 CRC patients, three mitochondrial prognostic genes were eventually selected out, including HIGD1A, SUCLG2, and SLC25A24. The expression of HIGD1A exhibited a significant reduction in two subtypes of adenoma and six subtypes of CRC, while the down-regulation of SUCLG2 and SLC25A24 showed more advantages in rectal mucinous adenocarcinoma. Moreover, we unveiled that these three genes had common expressions and might collaboratively participate in the synthesis of ribosomes. Our original multi-omics datasets, including DNA methylation, structural variants, chromatin accessibility, and phosphoproteome, further depicted the altered modifications on their potential transcriptional factors. Conclusions In summary, HIGD1A, SUCLG2, and SLC25A24 might serve as predictive biomarkers for CRC. The biological activities they involved in and their upstream regulators we uncovered would provide a functional context for the further-in-depth mechanism study. Graphic abstract

Abstract Background Trisomy 18 syndrome (Edwards syndrome, ES) is a type of aneuploidy caused by the presence of an extra chromosome 18. Aneuploidy is the leading cause of early pregnancy loss, intellectual disability, and multiple congenital anomalies. The research of trisomy 18 is progressing slowly, and the molecular characteristics of the disease mechanism and phenotype are still largely unclear. Results In this study, we used the commercial Chromium platform (10× Genomics) to perform sc-ATAC-seq to measure chromatin accessibility in 11,611 single umbilical cord blood cells derived from one trisomy 18 syndrome patient and one healthy donor. We obtained 13 distinct major clusters of cells and identified them as 6 human umbilical cord blood mononuclear cell types using analysis tool. Compared with the NC group, the ES group had a lower ratio of T cells to NK cells, the ratio of monocytes/DC cell population did not change significantly, and the ratio of B cell nuclear progenitor and megakaryocyte erythroid cells was higher. The differential genes of ME-0 are enriched in Human T cell leukemia virus 1 infection pathway, and the differential peak genes of ME-1 are enriched in apopotosis pathway. We found that CCNB2 and MCM3 may be vital to the development of trisomy 18. CCNB2 and MCM3, which have been reported to be essential components of the cell cycle and chromatin. Conclusions We have identified 6 cell populations in cord blood. Disorder in megakaryocyte erythroid cells implicates trisomy 18 in perturbing fetal hematopoiesis. We identified a pathway in which the master differential regulatory pathway in the ME-0 cell population involves human T cell leukemia virus 1 infection, a pathway that is dysregulated in patients with trisomy 18 and which may increase the risk of leukemia in patients with trisomy 18. CCNB2 and MCM3 in progenitor may be vital to the development of trisomy 18. CCNB2 and MCM3, which have been reported to be essential components of the cell cycle and chromatin, may be related to chromosomal abnormalities in trisomy 18.

When people talk about kinship systems, they often use co‐speech gestures and other representations to elaborate. This paper investigates such polysemiotic (spoken, gestured, and drawn) descriptions of kinship relations, to see if they display recurring patterns of conventionalization that capture specific social structures. We present an exploratory hypothesis‐generating study of descriptions produced by a lesser‐known ethnolinguistic community to the cognitive sciences: the Paamese people of Vanuatu. Forty Paamese speakers were asked to talk about their family in semi‐guided kinship interviews. Analyses of the speech, gesture, and drawings produced during these interviews revealed that lineality (i.e., mother's side vs. father's side) is lateralized in the speaker's gesture space. In other words, kinship members of the speaker's matriline are placed on the left side of the speaker's body and those of the patriline are placed on their right side, when they are mentioned in speech. Moreover, we find that the gesture produced by Paamese participants during verbal descriptions of marital relations are performed significantly more often on two diagonal directions of the sagittal axis. We show that these diagonals are also found in the few diagrams that participants drew on the ground to augment their verbo‐gestural descriptions of marriage practices with drawing. We interpret this behavior as evidence of a spatial template, which Paamese speakers activate to think and communicate about family relations. We therefore argue that extending investigations of kinship structures beyond kinship terminologies alone can unveil additional key factors that shape kinship cognition and communication and hereby provide further insights into the diversity of social structures. [ABSTRACT FROM AUTHOR]

Abstract Chromoanagenesis is a catastrophic event that involves localized chromosomal shattering and reorganization. In this study, we report a case of chromoanagenesis resulting from defective meiosis in the MEIOTIC ASYNAPTIC MUTANT 1 (asy1Arabidopsis thalianaasy1- Plain Language SummaryChromoanagenesis is a complex and catastrophic event that results in severely restructured chromosomes. It has been identified in cancer cells and in some plant samples, after specific triggering events. Here, we identified this kind of genome restructuring in a mutant that exhibits defective meiosis in the model plant system Arabidopsis thaliana