Draft Genome Sequence of Frankia sp. Strain QA3, a Nitrogen-Fixing Actinobacterium Isolated from the Root Nodule of Alnus nitida

Members of the actinomycete genus Frankia form a nitrogen-fixing symbiosis with 8 different families of actinorhizal plants. We report a high-quality draft genome sequence for Frankia sp. strain QA3, a nitrogen-fixing actinobacterium isolated from root nodules of Alnus nitida

Draft Genome Sequence of Frankia sp. Strain CN3, an Atypical, Noninfective (Nod–) Ineffective (Fix–) Isolate from Coriaria nepalensis

We report here the genome sequence of Frankia sp. strain CN3, which was isolated from Coriaria nepalensis. This genome sequence is the first from the fourth lineage of Frankia, strains of which are unable to reinfect actinorhizal plants. At 10 Mb, it represents the largest Frankia genome sequenced to date

Angiotensin-(1–7)/Mas axis integrity is required for the expression of object recognition memory

AbstractIt has been shown that the brain has its own intrinsic renin–angiotensin system (RAS) and angiotensin-(1–7) (Ang-(1–7)) is particularly interesting, because it appears to counterbalance most of the Ang II effects. Ang-(1–7) exerts its biological function through activation of the G-protein-coupled receptor Mas. Interestingly, hippocampus is one of the regions with higher expression of Mas. However, the role of Ang-(1–7)/Mas axis in hippocampus-dependent memories is still poorly understood. Here we demonstrated that Mas ablation, as well as the blockade of Mas in the CA1-hippocampus, impaired object recognition memory (ORM). We also demonstrated that the blockade of Ang II receptors AT1, but not AT2, recovers ORM impairment of Mas-deficient mice. Considering that high concentrations of Ang-(1–7) may activate AT1 receptors, nonspecifically, we evaluate the levels of Ang-(1–7) and its main precursors Ang I and Ang II in the hippocampus of Mas-deficient mice. The Ang I and Ang II levels are unaltered in the whole hipocampus of MasKo. However, Ang-(1–7) concentration is increased in the whole hippocampus of MasKo mice, as well as in the CA1 area. Taken together, our findings suggest that the functionality of the Ang-(1–7)/Mas axis is essential for normal ORM processing

Functional specificity of the members of the Sos family of Ras-GEF Activators: Novel role of Sos2 in control of epidermal stem cell homeostasis

© 2021 by the authors.Prior reports showed the critical requirement of Sos1 for epithelial carcinogenesis, but the specific functionalities of the homologous Sos1 and Sos2 GEFs in skin homeostasis and tumorigenesis remain unclear. Here, we characterize specific mechanistic roles played by Sos1 or Sos2 in primary mouse keratinocytes (a prevalent skin cell lineage) under different experimental conditions. Functional analyses of actively growing primary keratinocytes of relevant genotypes—WT, Sos1-KO, Sos2-KO, and Sos1/2-DKO—revealed a prevalent role of Sos1 regarding transcriptional regulation and control of RAS activation and mechanistic overlapping of Sos1 and Sos2 regarding cell proliferation and survival, with dominant contribution of Sos1 to the RAS-ERK axis and Sos2 to the RAS-PI3K/AKT axis. Sos1/2-DKO keratinocytes could not grow under 3D culture conditions, but single Sos1-KO and Sos2-KO keratinocytes were able to form pseudoepidermis structures that showed disorganized layer structure, reduced proliferation, and increased apoptosis in comparison with WT 3D cultures. Remarkably, analysis of the skin of both newborn and adult Sos2-KO mice uncovered a significant reduction of the population of stem cells located in hair follicles. These data confirm that Sos1 and Sos2 play specific, cell-autonomous functions in primary keratinocytes and reveal a novel, essential role of Sos2 in control of epidermal stem cell homeostasis.The E.S. group was supported by grants from ISCIII-MCUI (FIS PI19/00934), JCyL (SA264P18-UIC 076), Areces Foundation (CIVP19A5942), Solorzano-Barruso Foundation (FS/32-2020), and by ISCIII-CIBERONC (group CB16/12/00352). Research was co-financed by FEDER funds. The J.M.P. lab is co-funded by European Regional Development Fund (FEDER) grants from Science and Innovation (SAF2015-66015-R and PID2019-110758RB-I00 to J.M.P.) and Instituto de Salud Carlos III (CIBERONC no. CB16/12/00228 to J.M.P.). The XRB lab is funded by “la Caixa” Banking Foundation (HR20-00164), the Castilla-León autonomous government (CSI252P18, CSI145P20, CLC-2017-01), the Spanish Ministry of Science and Innovation (MSI) (RTI2018-096481-B-100), and the Spanish Association against Cancer (GC16173472GARC). The CIC is supported by the Programa de Apoyo a Planes Estratégicos de Investigación de Estructuras de Investigación de Excelencia of the Castilla-León autonomous government (CLC-2017-01). L.F.L.-M. and N.F.-P. contracts have been supported by funding from the Spanish Ministry of Universities (FPU13/02923, FPU17/03912) and, in the case of L.F.L.M., by CLC-2017-01 grant

Standardization of in vitro digestibility and DIAAS method based on the static INFOGEST protocol

Resumen de la conferencia invitada presentada en el 7th International Conference on Food Digestion. Cork, Irlanda. 3-5 Mayo (2022

A localized outbreak of Chikungunya virus in Salvador, Bahia, Brazil

A localized Chikungunya virus (CHIKV; East/Central/South African genotype) outbreak (50 cases, 70% laboratory-confirmed; attack rate: 5.3 confirmed cases/100 people) occurred in a Salvador, Brazil neighborhood, between Apr-Jun/2017. Highly clustered cases in space and time, mostly along a single street, highlight an increased risk of CHIKV transmission among pockets of susceptible populations. This finding underscores the need for ongoing local level surveillance for arboviral outbreaks.Fil: Tauro, Laura Beatriz. Fundación Oswaldo Cruz; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Puerto Iguazú | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Puerto Iguazú; ArgentinaFil: Cardoso, Cristiane W.. Secretaria Municipal da Saúde de Salvador; BrasilFil: Souza, Raquel L.. Fundación Oswaldo Cruz; BrasilFil: Nascimento, Leile Cj. Fundación Oswaldo Cruz; BrasilFil: Santos, Daniela R Dos. Secretaria Municipal da Saúde de Salvador; BrasilFil: Campos, Gubio S.. Universidade Federal da Bahia; BrasilFil: Ferro Sardi, Silvia Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidade Federal da Bahia; BrasilFil: Reis, Olivete B Dos. Secretaria Municipal da Saúde de Salvador; BrasilFil: Reis, Mitermayer G.. Fundación Oswaldo Cruz; Brasil. Universidade Federal da Bahia; Brasil. University of Yale; Estados UnidosFil: Kitron, Uriel D.. Fundación Oswaldo Cruz; Brasil. University of Emory; Estados UnidosFil: Ribeiro, Guilherme S.. Universidade Federal da Bahia; Brasil. Fundación Oswaldo Cruz; Brasi

A large, ten-generation family with autosomal dominant preaxial polydactyly/triphalangeal thumb: Historical, clinical, genealogical, and molecular studies

We present a large, ten-generation family of 273 individuals with 84 people having preaxial polydactyly/triphalangeal thumb due to a pathogenic variant in the zone of polarizing activity regulatory sequence (ZRS) within the exon 5 of LMBR1. The causative change maps to position 396 of the ZRS, located at position c.423 + 4909C > T (chr7:156791480; hg38; LMBR1 ENST00000353442.10; rs606231153 NG_009240.2) in the intron 5 of LMBR1. The first affected individual with the disorder was traced back to mid-1700, when some settlers and workers established in Cervera de Buitrago, a small village about 82 km North to Madrid. Clinical and radiological studies of most of the affected members have been performed for 42 years (follow-up of the family by LFGA). Molecular studies have confirmed a pathogenic variant in the ZRS that segregates in this family. To the best of our knowledge, this is the largest family with preaxial polydactyly/triphalangeal thumb reported so far.Instituto de Salud Carlos III, Grant/Award Number: PI20/0105

Improved personalized survival prediction of patients with diffuse large B-cell Lymphoma using gene expression profiling

BACKGROUND: Thirty to forty percent of patients with Diffuse Large B-cell Lymphoma (DLBCL) have an adverse clinical evolution. The increased understanding of DLBCL biology has shed light on the clinical evolution of this pathology, leading to the discovery of prognostic factors based on gene expression data, genomic rearrangements and mutational subgroups. Nevertheless, additional efforts are needed in order to enable survival predictions at the patient level. In this study we investigated new machine learning-based models of survival using transcriptomic and clinical data. METHODS: Gene expression profiling (GEP) of in 2 different publicly available retrospective DLBCL cohorts were analyzed. Cox regression and unsupervised clustering were performed in order to identify probes associated with overall survival on the largest cohort. Random forests were created to model survival using combinations of GEP data, COO classification and clinical information. Cross-validation was used to compare model results in the training set, and Harrel's concordance index (c-index) was used to assess model's predictability. Results were validated in an independent test set. RESULTS: Two hundred thirty-three and sixty-four patients were included in the training and test set, respectively. Initially we derived and validated a 4-gene expression clusterization that was independently associated with lower survival in 20% of patients. This pattern included the following genes: TNFRSF9, BIRC3, BCL2L1 and G3BP2. Thereafter, we applied machine-learning models to predict survival. A set of 102 genes was highly predictive of disease outcome, outperforming available clinical information and COO classification. The final best model integrated clinical information, COO classification, 4-gene-based clusterization and the expression levels of 50 individual genes (training set c-index, 0.8404, test set c-index, 0.7942). CONCLUSION: Our results indicate that DLBCL survival models based on the application of machine learning algorithms to gene expression and clinical data can largely outperform other important prognostic variables such as disease stage and COO. Head-to-head comparisons with other risk stratification models are needed to compare its usefulness

Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variants

Irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction frequently accompanied by mental conditions, including depression and anxiety. Despite showing substantial heritability and being partly determined by a genetic component, the genetic underpinnings explaining the high rates of comorbidity remain largely unclear and there are no conclusive data on the temporal relationship between them. Exploring the overlapping genetic architecture between IBS and mental conditions may help to identify novel genetic loci and biological mechanisms underlying IBS and causal relationships between them. We quantified the genetic overlap between IBS, neuroticism, depression and anxiety, conducted a multi-trait genome-wide association study (GWAS) considering these traits and investigated causal relationships between them by using the largest GWAS to date. IBS showed to be a highly polygenic disorder with extensive genetic sharing with mental conditions. Multi-trait analysis of IBS and neuroticism, depression and anxiety identified 42 genome-wide significant variants for IBS, of which 38 are novel. Fine-mapping risk loci highlighted 289 genes enriched in genes upregulated during early embryonic brain development and gene-sets related with psychiatric, digestive and autoimmune disorders. IBS-associated genes were enriched for target genes of anti-inflammatory and antirheumatic drugs, anesthetics and opioid dependence pharmacological treatment. Mendelian-randomization analysis accounting for correlated pleiotropy identified bidirectional causal effects between IBS and neuroticism and depression and causal effects of the genetic liability of IBS on anxiety. These findings provide evidence of the polygenic architecture of IBS, identify novel genome-wide significant variants for IBS and extend previous knowledge on the genetic overlap and relationship between gastrointestinal and mental disorders. The online version contains supplementary material available at 10.1186/s12967-023-04107-5