EMT: Matter of Life or Death?

TGF-ß is long considered a "protean" cytokine in cancer, changing its role from anti- to pro-tumorigenic in a context-dependent manner. In this issue of Cell, David et al. use mouse models of pancreatic cancer to shed light on the mechanistic basis of how TGF-ß-induced EMT is coupled to either apoptosis or tumor progression.

SeqCode: A Nomenclatural Code for Prokaryotes.

SeqCode is a nomenclatural code for naming prokaryotes based on genetic information. With the majority of prokaryotes being inaccessible as pure cultures, they are not eligible for naming under the International Code of Nomenclature of Prokaryotes. To address this challenge, a new concept that is SeqCode, which assign names to prokaryotes on the basis of genome sequence, has been announced in 2022. The valid publication of names for prokaryotes based on isolated genome, metagenome-assembled genomes, or single-amplified genome sequences. It operates through a registration portal, SeqCode Registry, where metadata is linked to names and nomenclatural types. This code provides a framework for reproducible nomenclature for all prokaryotes, either culturable or not and facilitates communication across all microbiological disciplines. Additionally, the SeqCode includes provisions for updating and revising names as new data becomes available. By providing a standardized system for naming and classifying these microorganisms based on their genetic information, the SeqCode will facilitate the discovery, understanding and comparison of these microorganisms, helping us to understand their role in the environment and how they contribute to the functioning of the Earth.

Interchromosomal linkage disequilibrium and linked fitness cost loci associated with selection for herbicide resistance.

The adaptation of weeds to herbicide is both a significant problem in agriculture and a model of rapid adaptation. However, significant gaps remain in our knowledge of resistance controlled by many loci and the evolutionary factors that influence the maintenance of resistance. Here, using herbicide-resistant populations of the common morning glory (Ipomoea purpurea), we perform a multilevel analysis of the genome and transcriptome to uncover putative loci involved in nontarget-site herbicide resistance (NTSR) and to examine evolutionary forces underlying the maintenance of resistance in natural populations. We found loci involved in herbicide detoxification and stress sensing to be under selection and confirmed that detoxification is responsible for glyphosate (RoundUp) resistance using a functional assay. We identified interchromosomal linkage disequilibrium (ILD) among loci under selection reflecting either historical processes or additive effects leading to the resistance phenotype. We further identified potential fitness cost loci that were strongly linked to resistance alleles, indicating the role of genetic hitchhiking in maintaining the cost. Overall, our work suggests that NTSR glyphosate resistance in I. purpurea is conferred by multiple genes which are potentially maintained through generations via ILD, and that the fitness cost associated with resistance in this species is likely a by-product of genetic hitchhiking.

Comorbidities in psoriatic arthritis: a systematic review and meta-analysis.

The aims of this systematic review and meta-analysis were to: (1) describe the prevalence of commonly reported comorbidities in psoriatic arthritis (PsA), (2) compare the incidence and/or prevalence of comorbidities between PsA and control populations; and (3) examine the impact of comorbidities on PsA outcomes. We systematically searched Medline, PubMed, Scopus, and Web of Science using a predefined protocol in accordance with PRISMA guidelines. Studies reporting only one comorbidity, or a few closely related diseases within one organ system, were excluded. Where possible, meta-analysis was performed using random-effects models. We included 39 studies amounting to over 152 thousand PsA patients. We performed meta-analysis for the prevalence of 21 commonly reported comorbidities. The most prevalent comorbidities were hypertension (pooled prevalence 34%), metabolic syndrome (29%), obesity (27%), hyperlipidaemia (24%) and any cardiovascular diseases (19%). Eleven studies consistently showed higher prevalence of comorbidities in PsA than controls. Five studies showed that comorbid patients had more severe disease, poorer quality of life, and increased discontinuation of treatment. Comorbidities, particularly cardiometabolic disorders, were highly prevalent in PsA and more common than in healthy controls. Comorbidities were associated with adverse disease features, but more research is needed on their impact on longitudinal outcomes such as treatment response, work productivity and mortality.

The incidence and prevalence of cardiovascular diseases in gout: a systematic review and meta-analysis.

The aims of this systematic review and meta-analysis were to describe prevalence of cardiovascular disease in gout, compare these results with non-gout controls and consider whether there were differences according to geography. PubMed, Scopus and Web of Science were systematically searched for studies reporting prevalence of any cardiovascular disease in a gout population. Studies with non-representative sampling, where a cohort had been used in another study, small sample size (< 100) and where gout could not be distinguished from other rheumatic conditions were excluded, as were reviews, editorials and comments. Where possible meta-analysis was performed using random-effect models. Twenty-six studies comprising 949,773 gout patients were included in the review. Pooled prevalence estimates were calculated for five cardiovascular diseases: myocardial infarction (2.8%; 95% confidence interval (CI)s 1.6, 5.0), heart failure (8.7%; 95% CI 2.9, 23.8), venous thromboembolism (2.1%; 95% CI 1.2, 3.4), cerebrovascular accident (4.3%; 95% CI 1.8, 9.7) and hypertension (63.9%; 95% CI 24.5, 90.6). Sixteen studies reported comparisons with non-gout controls, illustrating an increased risk in the gout group across all cardiovascular diseases. There were no identifiable reliable patterns when analysing the results by country. Cardiovascular diseases are more prevalent in patients with gout and should prompt vigilance from clinicians to the need to assess and stratify cardiovascular risk. Future research is needed to investigate the link between gout, hyperuricaemia and increased cardiovascular risk and also to establish a more thorough picture of prevalence for less common cardiovascular diseases.

Altered hydroxymethylation is seen at regulatory regions in pancreatic cancer and regulates oncogenic pathways.

Transcriptional deregulation of oncogenic pathways is a hallmark of cancer and can be due to epigenetic alterations. 5-Hydroxymethylcytosine (5-hmC) is an epigenetic modification that has not been studied in pancreatic cancer. Genome-wide analysis of 5-hmC-enriched loci with hmC-seal was conducted in a cohort of low-passage pancreatic cancer cell lines, primary patient-derived xenografts, and pancreatic controls and revealed strikingly altered patterns in neoplastic tissues. Differentially hydroxymethylated regions preferentially affected known regulatory regions of the genome, specifically overlapping with known H3K4me1 enhancers. Furthermore, base pair resolution analysis of cytosine methylation and hydroxymethylation with oxidative bisulfite sequencing was conducted and correlated with chromatin accessibility by ATAC-seq and gene expression by RNA-seq in pancreatic cancer and control samples. 5-hmC was specifically enriched at open regions of chromatin, and gain of 5-hmC was correlated with up-regulation of the cognate transcripts, including many oncogenic pathways implicated in pancreatic neoplasia, such as MYC, KRAS, VEGFA, and BRD4 Specifically, BRD4 was overexpressed and acquired 5-hmC at enhancer regions in the majority of neoplastic samples. Functionally, acquisition of 5-hmC at BRD4 promoter was associated with increase in transcript expression in reporter assays and primary samples. Furthermore, blockade of BRD4 inhibited pancreatic cancer growth in vivo. In summary, redistribution of 5-hmC and preferential enrichment at oncogenic enhancers is a novel regulatory mechanism in human pancreatic cancer.

The remarkable morphological diversity of leaf shape in sweet potato (Ipomoea batatas): the influence of genetics, environment, and G×E.

Leaf shape, a spectacularly diverse plant trait, varies across taxonomic levels, geography and in response to environmental differences. However, comprehensive intraspecific analyses of leaf shape variation across variable environments is surprisingly absent. Here, we performed a multilevel analysis of leaf shape using diverse accessions of sweet potato (Ipomoea batatas), and uncovered the role of genetics, environment, and G×E on this important trait. We examined leaf shape using a variety of morphometric analyses, and complement this with a transcriptomic survey to identify gene expression changes associated with shape variation. Additionally, we examined the role of genetics and environment on leaf shape by performing field studies in two geographically separate common gardens. We showed that extensive leaf shape variation exists within I. batatas, and identified promising candidate genes associated with this variation. Interestingly, when considering traditional measures, we found that genetic factors are largely responsible for most of leaf shape variation, but that the environment is highly influential when using more quantitative measures via leaf outlines. This extensive and multilevel examination of leaf shape shows an important role of genetics underlying a potentially important agronomic trait, and highlights that the environment can be a strong influence when using more quantitative measures of leaf shape.

Prevalence of extra-articular manifestations in psoriatic arthritis: a systematic review and meta-analysis.

OBJECTIVE: To describe the prevalence of extra-articular manifestations-enthesitis, dactylitis, nail disease, uveitis and IBD-in PsA, and their impact on longitudinal disease outcomes. METHODS: We searched Medline, PubMed, Scopus and Web of Science using a predefined protocol in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies using imaging to define extra-articular manifestations (EAMs) were excluded. Where possible, we performed meta-analyses of prevalence estimates, reported as percentages (95% CI). Heterogeneity (I2 statistic) was examined according to study characteristics. RESULTS: We identified 65 studies amounting to a total of 163 299 PsA patients. Enthesitis was assessed in 29 studies with an average prevalence of 30% (95% CI: 24%, 38%). Dactylitis was reported in 35 studies with an average prevalence of 25% (95% CI: 20%, 31%). Nail disease was present in 60% (95% CI: 52%, 68%) across 26 studies, but definitions were often unclear. Uveitis (3.2%; 95% CI: 1.9%, 5.3%) and IBD (3.3%; 95% CI: 1.5%, 7.1%) were less common. Heterogeneity was high (>95%) in all meta-analyses, but could not be explained by study characteristics. No studies examined the impact of EAMs on longitudinal disease outcomes, except that dactylitis increases radiographic progression. CONCLUSION: Enthesitis, dactylitis and nail disease are highly prevalent in PsA, but not uveitis and IBD. EAM patterns differ from axial SpA despite their shared disease mechanisms, which may help further understand differences between spondyloarthritides. More studies are needed on the impact of EAMs on disease outcomes such as response to treatment.

Correction to: Enhanced uptake, high selective and microtubule disrupting activity of carbohydrate fused pyrano-pyranones derived from natural coumarins attributes to its anti-malarial potential.

Please note, following publication of the original article [1], the authors have advised of two errors that are present in the published article.

The prevalence and impact of depression in primary systemic vasculitis: a systematic review and meta-analysis.

OBJECTIVE: To describe the prevalence of depression among patients with primary systemic vasculitides (PSV); compare prevalence according to vasculitis type and against controls; and examine the impact of depression on PSV outcomes. METHODS: We searched Medline, PubMed, Scopus and Web of Science using a predefined protocol in accordance with PRISMA guidelines. We included all studies that reported the prevalence or impact of depression in PSV. We also included polymyalgia rheumatica (PMR) given its association with giant cell arteritis (GCA). Meta-analyses of prevalence estimates were performed using random-effects models and reported as percentages (95% confidence interval). RESULTS: We reviewed a total of 15 studies that described the prevalence of depression, categorised into small (n = 10) and large vessel vasculitis (n = 7). Pooled prevalence estimate for depression in a small vessel (predominantly ANCA-associated) vasculitis was 28% (95% CI 20-38%) with significant heterogeneity (I2 = 93%). Depression prevalence in large-vessel vasculitis (Takayasu and GCA/PMR) was 24% (95% CI 17-34%), again with significant heterogeneity (I2 = 96%). One study reported 56% prevalence of depression in medium vessel disease. The prevalence of depression in small vessel vasculitis was higher than healthy controls. In these patients, depression and depressive symptoms were associated with poorer quality of life, adherence, and work disability, but not disease activity or damage. CONCLUSION: Depression is highly prevalent among patients with primary systemic vasculitis and associated with poorer outcomes across a range of measures in studies of small vessel disease. Further studies are needed for depression in medium and large vessel vasculitides.