Broad Spectrum Of Diseases Research Articles

Intelligent reprogramming of wheat for enhancement of fungal and nematode disease resistance using advanced molecular techniques.

Wheat (Triticum aestivum L.) diseases are major factors responsible for substantial yield losses worldwide, which affect global food security. For a long time, plant breeders have been struggling to improve wheat resistance against major diseases by selection and conventional breeding techniques. Therefore, this review was conducted to shed light on various gaps in the available literature and to reveal the most promising criteria for disease resistance in wheat. However, novel techniques for molecular breeding in the past few decades have been very fruitful for developing broad-spectrum disease resistance and other important traits in wheat. Many types of molecular markers such as SCAR, RAPD, SSR, SSLP, RFLP, SNP, and DArT, etc., have been reported for resistance against wheat pathogens. This article summarizes various insightful molecular markers involved in wheat improvement for resistance to major diseases through diverse breeding programs. Moreover, this review highlights the applications of marker assisted selection (MAS), quantitative trait loci (QTL), genome wide association studies (GWAS) and the CRISPR/Cas-9 system for developing disease resistance against most important wheat diseases. We also reviewed all reported mapped QTLs for bunts, rusts, smuts, and nematode diseases of wheat. Furthermore, we have also proposed how the CRISPR/Cas-9 system and GWAS can assist breeders in the future for the genetic improvement of wheat. If these molecular approaches are used successfully in the future, they can be a significant step toward expanding food production in wheat crops.

Plant immune receptors can sequester and protect host proteins from pathogen-promoted degradation

Genetically controlled broad-spectrum disease resistance is a highly desired trait for crop improvement. It allows to reduce the use of pesticides in the field and helps to streamline the development of new varieties. More than 100 loci are known to control the resistance of rice (Oryza sativa) to the devastating fungal blast disease caused by Magnaporthe oryzae. Some of these loci are effective against a small set of pathogen isolates, while others protect against a broader range of pathogen variants (Ning et al., 2020).

Golgi-IP, a tool for multimodal analysis of Golgi molecular content

The Golgi is a membrane-bound organelle that is essential for protein and lipid biosynthesis. It represents a central trafficking hub that sorts proteins and lipids to various destinations or for secretion from the cell. The Golgi has emerged as a docking platform for cellular signaling pathways including LRRK2 kinase whose deregulation leads to Parkinson disease. Golgi dysfunction is associated with a broad spectrum of diseases including cancer, neurodegeneration, and cardiovascular diseases. To allow the study of the Golgi at high resolution, we report a rapid Golgi immunoprecipitation technique (Golgi-IP) to isolate intact Golgi mini-stacks for subsequent analysis of their content. By fusing the Golgi-resident protein TMEM115 to three tandem HA epitopes (GolgiTAG), we purified the Golgi using Golgi-IP with minimal contamination from other compartments. We then established an analysis pipeline using liquid chromatography coupled with mass spectrometry to characterize the human Golgi proteome, metabolome, and lipidome. Subcellular proteomics confirmed known Golgi proteins and identified proteins not previously associated with the Golgi. Metabolite profiling established the human Golgi metabolome and revealed the enrichment of uridine-diphosphate (UDP) sugars and their derivatives, which is consistent with their roles in protein and lipid glycosylation. Furthermore, targeted metabolomics validated SLC35A2 as the subcellular transporter for UDP-hexose. Finally, lipidomics analysis showed that phospholipids including phosphatidylcholine, phosphatidylinositol, and phosphatidylserine are the most abundant Golgi lipids and that glycosphingolipids are enriched in this compartment. Altogether, our work establishes a comprehensive molecular map of the human Golgi and provides a powerful method to study the Golgi with high precision in health and disease.

Spatial transcriptomics in human skin research.

Spatial transcriptomics is a revolutionary technique that enables researchers to characterise tissue architecture and localisation of gene expression. A plethora of technologies that map gene expression are currently being developed, aiming to facilitate spatially resolved, high-dimensional assessment of gene transcription in the context of human skin research. Knowing which gene is expressed by which cell and in which location within skin, facilitates understanding of skin function and dysfunction in both health and disease. In this review, we summarise the available spatial transcriptomic methods and we describe their application to a broad spectrum of dermatological diseases.

Targeting ferroptosis, a novel programmed cell death, for the potential of alcohol-related liver disease therapy.

Ferroptosis is a new iron-dependent cell death mode, which is different from the other types of programmed cell death, such as apoptosis, necrosis, and autophagy. Ferroptosis is characterized by a process in which fatal lipids from lipid peroxidation accumulate in cells and eventually lead to cell death. Alcohol-related liver disease (ALD) is a type of liver injury caused by excessive alcohol intake. Alcohol-related liver disease is a broad-spectrum disease category, which includes fatty liver, steatohepatitis, hepatitis, cirrhosis, and hepatocellular tumors. Recent studies have found that ferroptosis is involved in the pathological development of non-viral liver diseases. Therefore, ferroptosis may be an ideal target for the treatment of non-viral liver diseases. In this review article, we will elaborate the molecular mechanism and regulatory mechanism of ferroptosis, explore the key role of ferroptosis in the Alcohol-related liver disease process, and summarize the existing targeted ferroptosis drugs and their feasibility for the treatment of Alcohol-related liver disease.

Venous congestion assessment using the venous excess ultrasound score: strongest predictor of acute kidney injury in patients with acute coronary syndromes

Abstract Funding Acknowledgements Type of funding sources: None. Background Elevated mean central venous pressure is associated with an increased risk of acute kidney injury (AKI) in critically ill patients with a broad spectrum of cardiovascular diseases. Nowadays, it is possible to perform a non-invasive assessment of systemic venous congestion using the Venous Excess Ultrasound Score (VExUS) which may enable early identification of patients with increased risk of adverse renal outcomes. Purpose This study aimed to evaluate the association between venous congestion assessed with VExUS and the incidence of AKI in patients with acute coronary syndrome (ACS). Methods Venous congestion assessment using VExUS was performed in consecutive patients with ACS. Linear regression analysis was used to determine the variables associated with the highest measured serum creatinine (sCr) during hospitalization and the admission sCr. In addition, a multivariable logistic regression analysis was performed for assessing the independent risk factors for AKI, which was defined according to the KDIGO criteria. Results A total of 77 patients hospitalized with ACS were prospectively enrolled in this study. Nineteen (25.6%) patients developed AKI. Baseline chronic kidney disease, Killip-Kimball >II on admission, GRACE score, admission NTproBNP values, and VExUS were significantly higher in the AKI-group than in the non-AKI group. Baseline chronic kidney disease, admission NT-proBNP values, and VExUS were independent risk factors associated with the highest measured sCr and the admission sCr. In multivariable logistic regression analysis, the risk of AKI was significantly associated with baseline chronic kidney disease, admission NT-proBNP values, and VExUS. Conclusion Baseline chronic kidney disease, admission NT-proBNP values, and VExUS were significant independent predictors of AKI in patients with ACS.

Expression and role of SerpinE2 in cardiac fibrosis

Cardiac fibrosis is a common histological feature of a broad spectrum of cardiovascular diseases including myocardial infarction. Proteases and their inhibitors are known to be involved in the regulation of extracellular matrix deposition and remodeling. SerpinE2 is a serine protease inhibitor expressed within the myocardium, which targets thrombin and the proteases of the plasminergic system. This inhibitor has been shown to be involved in lung fibrosis and could be an actor of cardiac remodeling. To study SerpinE2 expression in human left ventricle biopsies, from organ donors (control) and recipient explanted patients. To evaluate SerpinE2 role in cardiac remodeling and fibrosis in the mouse TAC (transverse aortic constriction) model. LV biopsies from organ donors and recipient explanted patients were characterized by histology and classified. SerpinE2 mRNA and protein expression in human samples were assessed by RT-qPCR and Western-Blot after pulverization in liquid nitrogen. Immunofluorescence was used to characterize SerpinE2 expression within paraffin embedded biopsies sections. Wild-type (WT) and SerpinE2-deficient (KO) mice were subjected to 27G TAC model and cardiac function was followed weekly by echocardiography Doppler. After 4 weeks, mice were sacrificed, hearts were harvested and frozen in liquid nitrogen. Heart cryosections were then used for histological fibrosis analysis (Sirius red) or for RNA extraction and RT-qPCR. We found that SerpinE2 expression (mRNA and protein) was significantly increased (×2.5) in the infarcted zone of the biopsies from the LV of explanted patients, compared with non-infarcted area and control donors. SerpinE2 mRNA expression in these samples was also strongly correlated with the expression on type I and III collagens, and TGF-ß. Immunofluorescence assays showed that SerpinE2 protein was mainly detected within the fibrotic areas of the explanted donors. Echocardiography Doppler of 27G mice showed significant decrease in KO animals LV mass and thickness compared with WT counterparts. A significant 2.3 times decrease in type I collagen mRNA expression was observed in KO mice but this was not confirmed by Sirius red staining in heart sections. These data suggest that SerpinE2 could be an actor and/or a biomarker or cardiac fibrosis.

Preanalytic and Analytic Quality System Considerations in Noncoding RNA Biomarker Development for Clinical Diagnostics.

A frequent topic of biomedical research is the potential clinical use of non-coding (nc) RNAs as quantitative biomarkers for a broad spectrum of health and disease. However, ncRNA analyses have not been pressed into widespread diagnostic use. Strong preclinical evidence suggests obstacles in the translation and reproducibility of this type of biomarker which may result from preanalytical and analytical variation in the non-standardized processes used to collect, process, and store samples, as well as the substantive differences between small and long ncRNA. We performed a narrative review of selected literature, through the lens of key laboratory-developed test (LDT) regulations under the Clinical Laboratory Improvement Amendments (CLIA) in the United States, to study critical gaps in ncRNA validation studies. This review describes the leading candidate ncRNA subclasses, their biogenesis and cellular function, and identifies specific pre-analytical variables with disproportionate impact on testing performance. We summarize these findings with strategic recommendations to clinicians and biomedical scientists involved in the design, conduct, and translation of ncRNA biomarker development.

COVID-19 and Related Vaccinations in Children: Pathogenic Aspects of Oral Lesions.

Various clinical manifestations of SARS-CoV-2 infections and adverse reactions to COVID-19 vaccination have been described in children. The present narrative review aimed to collect and synthesize reported findings on oral lesions detected in SARS-CoV-2-positive subjects following COVID-19 EMA-authorized and WHO Emergency Use Listing-approved vaccine administration in the pediatric population to detail their clinical features and highlight possible pathogenic aspects of those lesions based on current evidence. Few and incomplete reports were retrieved from the literature, probably because most lesions belonged to a broad spectrum of systemic diseases and syndromes and were nonspecific or inaccurately described. The most common oral lesions in pediatric SARS-CoV-2-positive patients were erosive-ulcerative lesions and macules/petechiae, primarily erythematous. In the context of COVID-19 vaccination, oral adverse reactions were rare and typically presented as erosive-ulcerative lesions, with EM-like or unspecified patterns. Future studies should investigate oral lesions in SARS-CoV-2-positive subjects and after COVID-19 vaccination in the pediatric population, taking into account viral variants and newly developed vaccines. Deeper insight into oral lesions detectable in pediatric SARS-CoV-2-positive subjects and after COVID-19 vaccination may increase clinicians' ability to improve multidisciplinary pediatric oral and general care.

Rice ubiquitin-conjugating enzyme OsUbc13 negatively regulates immunity against pathogens by enhancing the activity of OsSnRK1a.

Ubc13 is required for Lys63-linked polyubiquitination and innate immune responses in mammals, but its functions in plant immunity still remain largely unknown. Here, we used molecular biological, pathological, biochemical, and genetic approaches to evaluate the roles of rice OsUbc13 in response to pathogens. The OsUbc13-RNA interference (RNAi) lines with lesion mimic phenotypes displayed a significant increase in the accumulation of flg22- and chitin-induced reactive oxygen species, and in defence-related genes expression or hormones as well as resistance to Magnaporthe oryzae and Xanthomonas oryzae pv oryzae. Strikingly, OsUbc13 directly interacts with OsSnRK1a, which is the α catalytic subunit of SnRK1 (sucrose non-fermenting-1-related protein kinase-1) and acts as a positive regulator of broad-spectrum disease resistance in rice. In the OsUbc13-RNAi plants, although the protein level of OsSnRK1a did not change, its activity and ABA sensitivity were obviously enhanced, and the K63-linked polyubiquitination was weaker than that of wild-type Dongjin (DJ). Overexpression of the deubiquitinase-encoding gene OsOTUB1.1 produced similar effects with inhibition of OsUbc13 in affecting immunity responses, M. oryzae resistance, OsSnRK1a ubiquitination, and OsSnRK1a activity. Furthermore, re-interfering with OsSnRK1a in one OsUbc13-RNAi line (Ri-3) partially restored its M. oryzae resistance to a level between those of Ri-3 and DJ. Our data demonstrate OsUbc13 negatively regulates immunity against pathogens by enhancing the activity of OsSnRK1a.

Optimization of perioperative treatment strategies for locally advanced esophageal squamous cell carcinoma from the perspective of tumor heterogeneity

Recent advances in multimodality treatment offer excellent opportunities to rethink the paradigm of perioperative management for locally advanced esophageal squamous cell carcinoma. One treatment clearly doesn't fit all in terms of a broad disease spectrum. Individualized treatment of local control of bulky primary tumor burden (advanced T stage) or systemic control of nodal metastatic tumor burden (advanced N stage) is essential. Given that clinically applicable predictive biomarkers are still awaited, therapy selection guided by diverse phenotypes of tumor burden (T vs. N) is promising. Potential challenges regarding the use of immunotherapy may also boost this novel strategy in the future.

E063 Cardiac amyloidosis: a case series of 31 patients with a comprehensive literature review

Abstract Background/Aims Amyloidosis is a broad spectrum of heterogeneous diseases, characterized by the accumulation and extracellular deposit of misfolded proteins, resulting in organs’ thickening and dysfunction. Cardiac amyloidosis (CA) is common and represents an important key factor in patients’ prognosis. Our study aims to depict the profile of patients with CA, so as present their therapeutic management and outcomes. Methods We retrospectively carried out a descriptive study between 2015 and 2022, including all patients admitted to our department for systemic amyloidosis (SA) with confirmed cardiac involvement on echocardiography (TTE) and/or cardiac magnetic resonance (CMR). Results 31 patients were enrolled. The sex ratio (M/F) was 0.93 and the mean age was 62 ± 15 years (26-86). Past history included multiple myeloma (n = 7), monoclonal gammapathy of undetermined significance (n = 1), T lymphoma (n = 1), and systemic amyloidosis (n = 1). Cardiovascular risk factors comprised high blood pressure (25%), type 2 diabetes (15%), dyslipidemia (9%), and smoking (8%). Patients presented after a mean of 12 ± 4 months since the onset, with peripheral edema (68%) and other signs of right (53%) and global heart failure (19%). Concomitant extracardiac involvements were mainly renal (55%), mucocutaneous (20%), and neurological (16%). Electrocardiogram showed low-voltage (41%), poor R-wave progression (23%), atrial fibrillation (10%), atrioventricular block (6%), right bundle branch block (6%), left bundle branch block (6%), junctional tachycardia (6%), and left ventricular hypertrophy (LVH) (6%). On TTE, the features observed were the altered longitudinal global strain (93%) with a bull’s eye pattern (90%), LVH (90%), valvular and septal hypertrophy (88%), sparkling myocardium (65%), pericardial effusion (54%), diastolic dysfunction (37%), dilated cavities (35%), pulmonary hypertension (29%), and aortic stenosis (3%). Systolic function was mostly conserved (73%), at a mean of 53 ± 10%. The most recurrent signs on CMR were: late enhancement (90%), LVH (80%), and abnormalities in myocardium nulling (25%). Cardiac biomarkers included a Troponin of 0.35 ng/ml [0.13; 506] and BNP of 4895 pg/ml [1588; 13 224]. BS showed positive cardiac fixation (grade 2 or 3) in six cases, confirming ATTR-CA. Peripheral biopsies, serum and urine immunofixation, free light chains assays, and medullar investigations demonstrated AL in 23 patients. Two cases of AA were confirmed on immunohistochemistry, complicating sarcoidosis (n = 1) and ankylosing spondylitis (n = 1). Patients were treated with chemotherapy (n = 11), Tafamidis (n = 3), and Infliximab (n = 2). The outcomes documented were complete remission (n = 1), partial remission (n = 3), and death (n = 9) with a median survival of 7 months. Conclusion Our study highlights the grim prognosis still carried by CA patients. Although increased awareness is noticed among physicians, the disease is often discovered at a late stage or even overlooked. Further understanding of CA and prompt screening of at-risk patients are thus crucial for early diagnosis and management, in order to improve patients' outcomes. Disclosure S. Chadli: None. M. Maamar: None. H. Khibri: None. N. Moatassim: None. W. Ammouri: None. H. Harmouche: None. M. Adnaoui: None. Z. Tazi Mezalek: None.

POLG2-Linked Mitochondrial Disease: Functional Insights from New Mutation Carriers and Review of the Literature

Different pathogenic variants in the DNA polymerase-gamma2 (POLG2) gene cause a rare, clinically heterogeneous mitochondrial disease. We detected a novel POLG2 variant (c.1270 T > C, p.Ser424Pro) in a family with adult-onset cerebellar ataxia and progressive ophthalmoplegia. We demonstrated altered mitochondrial integrity in patients’ fibroblast cultures but no changes of the mitochondrial DNA were found when compared to controls. We consider this novel, segregating POLG2 variant as disease-causing in this family. Moreover, we systematically screened the literature for POLG2-linked phenotypes and re-evaluated all mutations published to date for pathogenicity according to current knowledge. Thereby, we identified twelve published, likely disease-causing variants in 19 patients only. The core features included progressive ophthalmoplegia and cerebellar ataxia; parkinsonism, neuropathy, cognitive decline, and seizures were also repeatedly found in adult-onset heterozygous POLG2-related disease. A severe phenotype relates to biallelic pathogenic variants in POLG2, i.e., newborn-onset liver failure, referred to as mitochondrial depletion syndrome. Our work underlines the broad clinical spectrum of POLG2-related disease and highlights the importance of functional characterization of variants of uncertain significance to enable meaningful genetic counseling.

Waist Circumference as a Risk Factor for Non-Alcoholic Fatty Liver Disease in Older Adults in Guayaquil, Ecuador.

A cross-sectional study was carried out in 99 older adults who regularly attended five gerontological centers in the city of Guayaquil, Ecuador. The variables studied were age, gender, independent life, access to complete meals, waist circumference, and NAFLD diagnosed by ultrasound. A significant relationship exists between waist circumference, body mass index, and fat mass percentage. However, only age and waist circumference were significant in the multivariate logistic regression model. Our results suggest that in the presence of waist circumference, body mass index loses its significance and age may be a protective factor due to adipose tissue loss and redistribution. Anthropometric measurements such as waist circumference can be used as complement indicators of NAFLD.

PD13-09 CLINICAL VALIDATION OF THE EAU2021 INTERMEDIATE RISK NMIBC DEFINITION AND IMPLICATIONS FOR ADJUVANT TREATMENT: A MULTICENTER YAU UROTHELIAL COLLABORATION

PD13-09 CLINICAL VALIDATION OF THE EAU2021 INTERMEDIATE RISK NMIBC DEFINITION AND IMPLICATIONS FOR ADJUVANT TREATMENT: A MULTICENTER YAU UROTHELIAL COLLABORATION

Non-emergency medical transportation practice in Shanghai

Background: To describe the current landscape of non-emergency medical transportation (NEMT) services in China’s mainland, and analyze information obtained from a private NEMT company in Shanghai. Methods: With regards to the NEMT environment in China’s mainland, we collected relevant NEMT policies from the websites of local Health Commissions, and collected business operating data from a Chinese enterprise information query tool, Qichacha. With regards to NEMT service in Shanghai, we analyzed operating data from 3426 trips by a professional NEMT company. Descriptive statistics were used to explain the characteristics of NEMT trips, and log-linear analyses were performed to compare the trips inside Shanghai with trips to/from other areas. Results: Of the 3426 trips in this study, there were 2962 trips inside Shanghai (86.5%) and 464 trips to/from other areas (13.5%), and the number of trips to/from each province was related to the distance to Shanghai. When comparing transportation types between trips inside Shanghai and to/from other areas, there was a significant difference (χ2=144.87, p<0.001), with a significantly larger proportion of trips for discharge to/from other areas, and a significantly larger proportion of referrals in trips inside Shanghai. Over 50% of trips were to orthopedics-featured class A tertiary hospitals. Discussion and Conclusion: To lower the NEMT service costs and bring benefit to patients with a broader spectrum of diseases, medical insurance could completely or partially cover NEMT services, and companies could initiate rideshare services. Shanghai is an attractive place for patients, with the highest level of healthcare resources. Transportation combining high-speed trains and NEMT vehicles ensures patients who live further away can access health care in Shanghai.

Yield and Chemical Composition of Ginger Essential Oils as Affected by Inter-Varietal Variation and Drying Treatments of Rhizome

Ginger (Zingiber officinale Rosc; Zingiberaceae family) is an herb commonly used as a spice and remedy for a broad spectrum of diseases. The essential oil extracted from ginger is an effective antioxidant, anti-inflammatory, and antifungal agent. The present study has investigated the variations in yield and chemical composition of essential oils of two cultivars (Chinese and Thailand) of ginger locally available in Pakistan. Two different drying pretreatments were employed to observe the changes in compositional variations of the essential oils of ginger. The essential oil extracted from fresh, oven-dried, and sun-dried samples of two different cultivars of ginger was analyzed using gas chromatography-mass spectrometry (GC-MS). The essential oil yield was found to be highest for the sun-dried sample of each variety. The major compounds (>4%) overall in the essential oil of fresh, oven-dried, and sun-dried ginger samples from Thailand origin were camphene, 3-carene, o-cymene, caryophyllene, α-curcumene, sabinol trans, citral, and santalol. Major compounds overall in the essential oil of fresh, oven-dried, and sun-dried ginger samples of Chinese origin were α-pinene, Camphene, limonene, longicyclene, copaene, longifolene, β-sesquiphellandrene, alloaromadendrene, γ-muurolene, α-curcumene, α-farnesene, and citral. The inter-varietal variations and pretreatment methods considerably affected yield and chemical composition. Cluster analysis was performed to validate the results further. Significantly varying compounds responsible for the significant variation among varieties and treatments of the ginger were identifies by using the heat map. There was clear differentiation among Chinese and Thailand varieties due to the variation in the concentrations of the volatile compounds. The results obtained can be helpful for the ginger growers and end users to choose the ginger variety and the way of use that is more beneficial.

Opioid induces increased DNA damage in prefrontal cortex and nucleus accumbens

Opioid use disorder (OUD) is a chronic disease characterized by compulsive opioid taking and seeking, affecting millions of people worldwide. The high relapse rate is one of the biggest challenges in treating opioid addiction. However, the cellular and molecular mechanisms underlying relapse to opioid seeking are still unclear. Recent studies have shown that DNA damage and repair processes are implicated in a broad spectrum of neurodegenerative diseases as well as in substance use disorders. In the present study, we hypothesized that DNA damage is related to relapse to heroin seeking. To test our hypothesis, we aim to examine the overall DNA damage level in prefrontal cortex (PFC) and nucleus accumbens (NAc) after heroin exposure, as well as whether manipulating DNA damage levels can alter heroin seeking. First, we observed increased DNA damage in postmortem PFC and NAc tissues from OUD individuals compared to healthy controls. Next, we found significantly increased levels of DNA damage in the dorsomedial PFC (dmPFC) and NAc from mice that underwent heroin self-administration. Moreover, increased accumulation of DNA damage persisted after prolonged abstinence in mouse dmPFC, but not in NAc. This persistent DNA damage was ameliorated by the treatment of reactive oxygen species (ROS) scavenger N-acetylcysteine, along with attenuated heroin-seeking behavior. Furthermore, intra-PFC infusions of topotecan and etoposide during abstinence, which trigger DNA single-strand breaks and double-strand breaks respectively, potentiated heroin-seeking behavior. These findings provide direct evidence that OUD is associated with the accumulation of DNA damage in the brain (especially in the PFC), which may lead to opioid relapse.

Genotype-phenotype mapping of a patient-derived lung cancer organoid biobank identifies NKX2-1-defined Wnt dependency in lung adenocarcinoma

Human lung cancer is a constellation of tumors with various histological and molecular properties. To build a preclinical platform that covers this broad disease spectrum, we obtained lung cancer specimens from multiple sources, including sputum and circulating tumor cells, and generated a living biobank consisting of 43 lines of patient-derived lung cancer organoids. The organoids recapitulated the histological and molecular hallmarks of the original tumors. Phenotypic screening of niche factor dependency revealed that EGFR mutations in lung adenocarcinoma are associated with the independence from Wnt ligands. Gene engineering of alveolar organoids reveals that constitutive activation of EGFR-RAS signaling provides Wnt independence. Loss of the alveolar identity gene NKX2-1 confers Wnt dependency, regardless of EGFR signal mutation. Sensitivity to Wnt-targeting therapy can be stratified by the expression status of NKX2-1. Our results highlight the potential of phenotype-driven organoid screening and engineering for the fabrication of therapeutic strategies to combat cancer.

Yersiniomics, a Multi-Omics Interactive Database for Yersinia Species.

The genus Yersinia includes a large variety of nonpathogenic and life-threatening pathogenic bacteria, which cause a broad spectrum of diseases in humans and animals, such as plague, enteritis, Far East scarlet-like fever (FESLF), and enteric redmouth disease. Like most clinically relevant microorganisms, Yersinia spp. are currently subjected to intense multi-omics investigations whose numbers have increased extensively in recent years, generating massive amounts of data useful for diagnostic and therapeutic developments. The lack of a simple and centralized way to exploit these data led us to design Yersiniomics, a web-based platform allowing straightforward analysis of Yersinia omics data. Yersiniomics contains a curated multi-omics database at its core, gathering 200 genomic, 317 transcriptomic, and 62 proteomic data sets for Yersinia species. It integrates genomic, transcriptomic, and proteomic browsers, a genome viewer, and a heatmap viewer to navigate within genomes and experimental conditions. For streamlined access to structural and functional properties, it directly links each gene to GenBank, the Kyoto Encyclopedia of Genes and Genomes (KEGG), UniProt, InterPro, IntAct, and the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and each experiment to Gene Expression Omnibus (GEO), the European Nucleotide Archive (ENA), or the Proteomics Identifications Database (PRIDE). Yersiniomics provides a powerful tool for microbiologists to assist with investigations ranging from specific gene studies to systems biology studies. IMPORTANCE The expanding genus Yersinia is composed of multiple nonpathogenic species and a few pathogenic species, including the deadly etiologic agent of plague, Yersinia pestis. In 2 decades, the number of genomic, transcriptomic, and proteomic studies on Yersinia grew massively, delivering a wealth of data. We developed Yersiniomics, an interactive web-based platform, to centralize and analyze omics data sets on Yersinia species. The platform allows user-friendly navigation between genomic data, expression data, and experimental conditions. Yersiniomics will be a valuable tool to microbiologists.