Comprehensive DNA metabarcoding-based detection of non-indigenous invertebrates in recreational marinas through a multi-substrate approach.

eDNA metabarcoding has been increasingly employed in the monitoring of marine invertebrate non-indigenous species (NIS), in particular using filtered seawater. However, comprehensive detection of all NIS may require a diversity of sampling substrates. To assess the effectiveness of 5 sample types (hard and artificial substrates, water, zooplankton) on the recovery of invertebrates' diversity, two marinas were monitored over three time points, using COI and 18S rRNA genes as DNA metabarcoding markers.

Therapeutic targeting of EP300/CBP by bromodomain inhibition in hematologic malignancies.

CCS1477 (inobrodib) is a potent, selective EP300/CBP bromodomain inhibitor which induces cell-cycle arrest and differentiation in hematologic malignancy model systems. In myeloid leukemia cells, it promotes rapid eviction of EP300/CBP from an enhancer subset marked by strong MYB occupancy and high H3K27 acetylation, with downregulation of the subordinate oncogenic network and redistribution to sites close to differentiation genes. In myeloma cells, CCS1477 induces eviction of EP300/CBP from FGFR3, the target of the common (4; 14) translocation, with redistribution away from IRF4-occupied sites to TCF3/E2A-occupied sites.

A TIAM1-TRIM28 complex mediates epigenetic silencing of protocadherins to promote migration of lung cancer cells.

Lung cancer is the leading cause of cancer deaths. Its high mortality is associated with high metastatic potential. Here, we show that the RAC1-selective guanine nucleotide exchange factor T cell invasion and metastasis-inducing protein 1 (TIAM1) promotes cell migration and invasion in the most common subtype of lung cancer, non-small-cell lung cancer (NSCLC), through an unexpected nuclear function.

Differentiation block in acute myeloid leukemia regulated by intronic sequences of .

Iroquois transcription factor gene is highly expressed in 20-30% of acute myeloid leukemia (AML) and contributes to the pathognomonic differentiation block. Intron 8 sequences ∼220kB downstream of exhibit histone acetylation, DNA methylation, and contacts with the promoter, which correlate with expression. Deletion of these intronic elements confirms a role in positively regulating .

Identification of curaxin as a potential new therapeutic for JAK2 V617F mutant patients.

Myelofibrosis is a myeloproliferative neoplasm (MPN) which typically results in reduced length and quality of life due to systemic symptoms and blood count changes arising from fibrotic changes in the bone marrow. While the JAK2 inhibitor ruxolitinib provides some clinical benefit, there remains a substantial unmet need for novel targeted therapies to better modify the disease process or eradicate the cells at the heart of myelofibrosis pathology. Repurposing drugs bypasses many of the hurdles present in drug development, such as toxicity and pharmacodynamic profiling.

A three-gene leukaemic stem cell signature score is robustly prognostic in chronic myelomonocytic leukaemia.

Leukaemic stem cell (LSC) gene expression has recently been linked to prognosis in patients with acute myeloid leukaemia (17-gene LSC score, LSC-17) and myelodysplastic syndromes. Although chronic myelomonocytic leukaemia (CMML) is regarded as a stem cell disorder, the clinical and biological impact of LSCs on CMML patients remains elusive. Making use of multiple independent validation cohorts, we here describe a concise three-gene expression signature (LSC-3, derived from the LSC-17 score) as an independent and robust prognostic factor for leukaemia-free and overall survival in CMML.

Pharmacological interventions for preventing venous thromboembolism in people undergoing bariatric surgery.

Background: Venous thromboembolism (VTE), which comprises deep vein thrombosis (DVT) and pulmonary embolism (PE), is the leading cause of preventable death in hospitalised people and the third most common cause of mortality in surgical patients. People undergoing bariatric surgery have the additional risk factor of being overweight. Although VTE prophylaxis in surgical patients is well established, the best way to prevent VTE in those undergoing bariatric surgery is less clear.

HMG20B stabilizes association of LSD1 with GFI1 on chromatin to confer transcription repression and leukemia cell differentiation block.

Pharmacologic inhibition of LSD1 induces molecular and morphologic differentiation of blast cells in acute myeloid leukemia (AML) patients harboring MLL gene translocations. In addition to its demethylase activity, LSD1 has a critical scaffolding function at genomic sites occupied by the SNAG domain transcription repressor GFI1. Importantly, inhibitors block both enzymatic and scaffolding activities, in the latter case by disrupting the protein:protein interaction of GFI1 with LSD1.

Microevolutionary dynamics show tropical valleys are deeper for montane birds of the Atlantic Forest.

Tropical mountains hold more biodiversity than their temperate counterparts, and this disparity is often associated with the latitudinal climatic gradient. However, distinguishing the impact of latitude versus the background effects of species history and traits is challenging due to the evolutionary distance between tropical and temperate assemblages. Here, we test whether microevolutionary processes are linked to environmental variation across a sharp latitudinal transition in 21 montane birds of the southern Atlantic Forest in Brazil.

Blast cells surviving acute myeloid leukemia induction therapy are in cycle with a signature of FOXM1 activity.

Background: Disease relapse remains common following treatment of acute myeloid leukemia (AML) and is due to chemoresistance of leukemia cells with disease repopulating potential. To date, attempts to define the characteristics of in vivo resistant blasts have focused on comparisons between leukemic cells at presentation and relapse. However, further treatment responses are often seen following relapse, suggesting that most blasts remain chemosensitive.

Enhancer recruitment of transcription repressors RUNX1 and TLE3 by mis-expressed FOXC1 blocks differentiation in acute myeloid leukemia.

Despite absent expression in normal hematopoiesis, the Forkhead factor FOXC1, a critical mesenchymal differentiation regulator, is highly expressed in ∼30% of HOXA acute myeloid leukemia (AML) cases to confer blocked monocyte/macrophage differentiation. Through integrated proteomics and bioinformatics, we find that FOXC1 and RUNX1 interact through Forkhead and Runt domains, respectively, and co-occupy primed and active enhancers distributed close to differentiation genes. FOXC1 stabilizes association of RUNX1, HDAC1, and Groucho repressor TLE3 to limit enhancer activity: FOXC1 knockdown induces loss of repressor proteins, gain of CEBPA binding, enhancer acetylation, and upregulation of nearby genes, including KLF2.

Towards Providing Effective Data-Driven Responses to Predict the Covid-19 in São Paulo and Brazil.

São Paulo is the most populous state in Brazil, home to around 22% of the country's population. The total number of Covid-19-infected people in São Paulo has reached more than 1 million, while its total death toll stands at 25% of all the country's fatalities. Joining the Brazilian academia efforts in the fight against Covid-19, in this paper we describe a unified framework for monitoring and forecasting the Covid-19 progress in the state of São Paulo.

Targeted nanopore sequencing for the identification of ABCB1 promoter translocations in cancer.

Background: Resistance to chemotherapy is the most common cause of treatment failure in acute myeloid leukemia (AML) and the drug efflux pump ABCB1 is a critical mediator. Recent studies have identified promoter translocations as common drivers of high ABCB1 expression in recurrent, chemotherapy-treated high-grade serous ovarian cancer (HGSC) and breast cancer. These fusions place ABCB1 under the control of a strong promoter while leaving its open reading frame intact.

EVI1 phosphorylation at S436 regulates interactions with CtBP1 and DNMT3A and promotes self-renewal.

The transcriptional regulator EVI1 has an essential role in early development and haematopoiesis. However, acute myeloid leukaemia (AML) driven by aberrantly high EVI1 expression has very poor prognosis. To investigate the effects of post-translational modifications on EVI1 function, we carried out a mass spectrometry (MS) analysis of EVI1 in AML and detected dynamic phosphorylation at serine 436 (S436).

Peripherally inserted central catheter versus central venous catheter for intravenous access: A protocol for systematic review and meta-analysis.

Background: Since the first description of the central venous catheter (CVC) in 1952, it has been used for the rapid administration of drugs, chemotherapy, as a route for nutritional support, blood components, monitoring patients, or combinations of these. When CVC is used in the traditional routes (eg, subclavian, jugular, and femoral veins), the complication rates range up to 15% and are mainly due to mechanical dysfunction, infection, and thrombosis. The peripherally inserted central catheter (PICC) is an alternative option for CVC access.

Climatic dynamics and topography control genetic variation in Atlantic Forest montane birds.

Montane organisms responded to Quaternary climate change by tracking suitable habitat along elevational gradients. However, it is unclear whether these past climatic dynamics generated predictable patterns of genetic diversity in co-occurring montane taxa. To test if the genetic variation is associated with historical changes in the elevational distribution of montane habitats, we integrated paleoclimatic data and a model selection approach for testing the demographic history of five co-distributed bird species occurring in the southern Atlantic Forest sky islands.

Adsorption kinetic and thermodynamic studies of the 2, 4 - dichlorophenoxyacetate (2,4-D) by the [Co-Al-Cl] layered double hydroxide.

[Co-Al-Cl] layered double hydroxide (LDH) obtained by co-precipitation at constant pH 8 presented a single phase in a hexagonal unit cell parameters similar to the hydrotalcite (JCPDS 14-191) belonging to the rhombohedral crystal system and space group . The adsorption kinetics of 2,4-D onto [Co-Al-Cl] LDH was better described by the Pseudo Second-Order (best adjust R = 0.9998 for 60 mg L 2,4-D adsorption).

Pre-clinical activity of combined LSD1 and mTORC1 inhibition in MLL-translocated acute myeloid leukaemia.

The histone demethylase lysine-specific demethylase 1 (LSD1 or KDM1A) has emerged as a candidate therapeutic target in acute myeloid leukaemia (AML); tranylcypromine-derivative inhibitors induce loss of clonogenic activity and promote differentiation, in particular in the MLL-translocated molecular subtype of AML. In AML, the use of drugs in combination often delivers superior clinical activity. To identify genes and cellular pathways that collaborate with LSD1 to maintain the leukaemic phenotype, and which could be targeted by combination therapies, we performed a genome-wide CRISPR-Cas9 dropout screen.

A stress-responsive enhancer induces dynamic drug resistance in acute myeloid leukemia.

The drug efflux pump ABCB1 is a key driver of chemoresistance, and high expression predicts treatment failure in acute myeloid leukemia (AML). In this study, we identified and functionally validated the network of enhancers that controls expression of ABCB1. We show that exposure of leukemia cells to daunorubicin activated an integrated stress response-like transcriptional program to induce ABCB1 through remodeling and activation of an ATF4-bound, stress-responsive enhancer.

Coordinated alterations in RNA splicing and epigenetic regulation drive leukaemogenesis.

Transcription and pre-mRNA splicing are key steps in the control of gene expression and mutations in genes regulating each of these processes are common in leukaemia. Despite the frequent overlap of mutations affecting epigenetic regulation and splicing in leukaemia, how these processes influence one another to promote leukaemogenesis is not understood and, to our knowledge, there is no functional evidence that mutations in RNA splicing factors initiate leukaemia. Here, through analyses of transcriptomes from 982 patients with acute myeloid leukaemia, we identified frequent overlap of mutations in IDH2 and SRSF2 that together promote leukaemogenesis through coordinated effects on the epigenome and RNA splicing.

Method for the determination of parameters in the sintering process of mixtures of the elemental powders Fe-Cr and Fe-Cr-Ni.

The achievement of varied metal alloys through the sintering of mixtures of elemental metallic powders can provide great flexibility of production of these alloys. The possibilities of controlling the composition and the resulting properties of the alloy are of great importance for metallurgy. Otherwise the alloys involving chromium offer many difficulties for their attainment through the process of powder metallurgy (PM).

Angioplasty and stenting for below the knee ulcers in diabetic patients: protocol for a systematic review.

Background: The worldwide incidence and prevalence of diabetes mellitus (DM) are increasing. DM has a high social and economic burden due to its complications and associated disorders. Peripheral arterial disease (PAD) is closely related to DM.