Histone H4 acetylation by immunohistochemistry and prognosis in newly diagnosed adult acute lymphoblastic leukemia (ALL) patients

Background: Histone deacetylase (HDAC) inhibitors are a novel anti-tumor therapy. To determine whether HDAC inhibitors may be useful in the treatment of adult acute lymphoblastic leukemia (ALL), we examined the acetylation of histone H4 by immunohistochemistry in newly diagnosed ALL patients and evaluated the impact of acetylation on complete remission (CR) rate, relapse-free survival (RFS), and overall survival (OS). Methods: Patients >= 18 years of age and an available diagnostic bone marrow biopsy were evaluated. Cox proportional hazards analysis was used to identify univariate and multivariate correlates of CR, RFS, and OS. The variables histone H4 acetylation (positive or negative), white blood count, cytogenetic (CG) risk group (CALGB criteria), and age were used in multivariate analysis. Results: On multivariate analysis, histone acetylation was associated with a trend towards an improved OS (for all CG risk groups) (HR = 0.51, p = 0.09). In patients without poor risk CG, there was an impressive association between the presence of histone acetylation and an improved CR rate (OR 3.43, p = 0.035), RFS (HR 0.07, p = 0.005), and OS (HR 0.24, p = 0.007). This association remained statistically significant in multivariate analysis. Conclusions: These data provide a rationale for the design of novel regimens incorporating HDAC inhibitors in ALL

Combining geostatistical and biotic interaction modelling to predict amphibian refuges under crayfish invasion across dendritic stream networks

Biodiversity ResearchAim: Biological invasions are pervasive in freshwater ecosystems, often causing native species to contract into areas that remain largely free from invasive species impacts. Predicting the location of such ecological refuges is challenging, because they are shaped by the habitat requirements of native and invasive species, their biotic interactions, and the spatial and temporal invasion patterns. Here, we investigated the spatial distribution and environmental drivers of refuges from invasion in river systems, by considering biotic interactions in geostatistical models accounting for stream network topology. We focused on Mediterranean amphibians negatively impacted by the invasive crayfishes Procambarus clarkii and Pacifastacus leniusculus. Location: River Sabor, NE Portugal. Methods: We surveyed amphibians at 168 200-m stream stretches in 2015. Geostatistical models were used to relate the probabilities of occurrence of each species to environmental and biotic variables, while controlling for linear (Euclidean) and hydrologic spatial dependencies. Biotic interactions were specified using crayfish probabilities of occurrence extracted from previously developed geostatistical models. Models were used to map the distribution of potential refuges for the most common amphibian species, under current conditions and future scenarios of crayfish expansion. Results: Geostatistical models were produced for eight out of 10 species detected, of which five species were associated with lower stream orders and only one species with higher stream orders. Six species showed negative responses to one or both crayfish species, even after accounting for environmental effects and spatial dependencies. Most amphibian species were found to retain large expanses of potential habitat in stream headwaters, but current refuges will likely contract under plausible scenarios of crayfish expansion. Main conclusions: Incorporating biotic interactions in geostatistical modelling provides a practical and relatively simple approach to predict present and future distributions of refuges from biological invasion in stream networks. Using this approach, our study shows that stream headwaters are key amphibian refuges under invasion by alien crayfishinfo:eu-repo/semantics/publishedVersio

Coalescent-based species delimitation in the sand lizards of the Liolaemus wiegmannii complex (Squamata: Liolaemidae)

Coalescent-based algorithms coupled with the access to genome-wide data have become powerful tools forassessing questions on recent or rapid diversification, as well as delineating species boundaries in the absence of reciprocal monophyly. In southern South America, the diversification of Liolaemus lizards during the Pleistocene is well documented and has been attributed to the climatic changes that characterized this recent period of time. Past climatic changes had harsh effects at extreme latitudes, including Patagonia, but habitat changes at intermediate latitudes of South America have also been recorded, including expansion of sand fields over northern Patagonia and Pampas). In this work, we apply a coalescent-based approach to study the diversification of the Liolaemus wiegmannii species complex, a morphologically conservative clade that inhabits sandy soils across northwest and south-central Argentina, and the south shores of Uruguay. Using four standard sequence markers (mitochondrial DNA and three nuclear loci) along with ddRADseq data we inferred species limits and a time calibrated species tree for the L. wiegmannii complex in order to evaluate the influence of Quaternary sand expansion/retraction cycles on diversification. We also evaluated the evolutionary independence of the recently described L. gardeli and inferred its phylogenetic position relative to L. wiegmannii. We find strong evidence for six allopatric candidate species within L. wiegmannii, which diversified during the Pleistocene. The Great Patagonian Glaciation (∼1 million years before present) likely split the species complex into two main groups: one composed of lineages associated with sub-Andean sedimentary formations, and the other mostly related to sand fields in the Pampas and northern Patagonia. We hypothesize that early speciation within L. wiegmannii was influenced by the expansion of sand dunes throughout central Argentina and Pampas. Finally, L. gardeli is supported as a distinct lineage nested within the L. wiegmannii complex.Fil: Villamil, Joaquín. Universidad de la República. Facultad de Ciencias; UruguayFil: Avila, Luciano Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; ArgentinaFil: Morando, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; ArgentinaFil: Sites, Jack W.. University Brigham Young; Estados UnidosFil: Leaché, Adam D.. University of Washington; Estados UnidosFil: Maneyro, Raúl. Universidad de la República. Facultad de Ciencias; UruguayFil: Camargo Bentaberry, Arley. Universidad de la República; Urugua

Prolonged Antibiotic Treatment does not Prevent Intra-Abdominal Abscesses in Perforated Appendicitis

Contains fulltext : 89619.pdf (publisher's version ) (Open Access)BACKGROUND: Children with perforated appendicitis have a relatively high risk of intra-abdominal abscesses. There is no evidence that prolonged antibiotic treatment after surgery reduces intra-abdominal abscess formation. We compared two patient groups with perforated appendicitis with different postoperative antibiotic treatment protocols. METHODS: We retrospectively reviewed patients younger than age 18 years who underwent appendectomy for perforated appendicitis at two academic hospitals between January 1992 and December 2006. Perforation was diagnosed during surgery and confirmed during histopathological evaluation. Patients in hospital A received 5 days of antibiotics postoperatively, unless decided otherwise on clinical grounds. Patients in hospital B received antibiotics for 5 days, continued until serum C-reactive protein (CRP) was <20 mg/l. Univariate logistic regression analysis was performed on intention-to-treat basis. p < 0.05 was considered significant. RESULTS: A total of 149 children underwent appendectomy for perforated appendicitis: 68 in hospital A, and 81 in hospital B. As expected, the median (range) use of antibiotics was significantly different: 5 (range, 1-16) and 7 (range, 2-32) days, respectively (p < 0.0001). However, the incidence of postoperative intra-abdominal abscesses was similar (p = 0.95). Regression analysis demonstrated that sex (female) was a risk factor for abscess formation, whereas surgical technique and young age were not. CONCLUSIONS: Prolonged use of antibiotics after surgery for perforated appendicitis in children based on serum CRP does not reduce postoperative abscess formation.1 december 201

Scanning Angle Plasmon Waveguide Resonance Raman Spectroscopy for the Analysis of Thin Polystyrene Films

Scanning angle (SA) Raman spectroscopy was used to characterize thin polymer films at a sapphire/50 nm gold film/polystyrene/air interface. When the polymer thickness is greater than ∼260 nm, this interface behaves as a plasmon waveguide; Raman scatter is greatly enhanced with both p- and s-polarized excitation compared to an interface without the gold film. In this study, the reflected light intensities from the interface and Raman spectra were collected as a function of incident angle for three samples with different polystyrene thicknesses. The Raman peak areas were well modeled with the calculated mean-square electric field (MSEF) integrated over the polymer film at varying incident angles. A 412 nm polystyrene plasmon waveguide generated 3.34× the Raman signal at 40.52° (the plasmon waveguide resonance angle) compared to the signal measured at 70.4° (the surface plasmon resonance angle). None of the studied polystyrene plasmon waveguides produced detectable Raman scatter using a 180° backscatter collection geometry, demonstrating the sensitivity of the SA Raman technique. The data highlight the ability to measure polymer thickness, chemical content, and, when combined with calculations of MSEF as a function of distance from the interface, details of polymer structure and order. The SA Raman spectroscopy thickness measurements agreed with those obtained from optical interferometery with an average difference of 2.6%. This technique has the potential to impact the rapidly developing technologies utilizing metal/polymer films for energy storage and electronic devices

Parvovirus B19 DNA CpG Dinucleotide Methylation and Epigenetic Regulation of Viral Expression

CpG DNA methylation is one of the main epigenetic modifications playing a role in the control of gene expression. For DNA viruses whose genome has the ability to integrate in the host genome or to maintain as a latent episome, a correlation has been found between the extent of DNA methylation and viral quiescence. No information is available for Parvovirus B19, a human pathogenic virus, which is capable of both lytic and persistent infections. Within Parvovirus B19 genome, the inverted terminal regions display all the characteristic signatures of a genomic CpG island; therefore we hypothesised a role of CpG dinucleotide methylation in the regulation of viral genome expression

Diagnosis, prognostic factors and assessment of ALL in adults: 2023 ELN recommendations from a European Expert Panel

Working groups of the European Leukemia Net (ELN) have published several important consensus guidelines. Acute lymphoblastic leukemia (ALL) has many different clinical and biological subgroups and the knowledge on disease biology and therapeutic options is increasing exponentially. The European Working Group for Adult ALL has therefore summarized the current state of the art and provided comprehensive consensus recommendations for diagnostic approaches, biologic and clinical characterization, prognostic factors and risk stratification as well as definitions of endpoints and outcomes. Aspects of treatment, management of subgroups and specific situations, aftercare and supportive care are covered in a separate publication. The present recommendation intends to provide guidance for the initial management of adult ALL patients and to define principles as a basis for future collaborative research

Genome sequencing reveals diversification of virulence factor content and possible host adaptation in distinct subpopulations of Salmonella enterica

<p>Abstract</p> <p>Background</p> <p>Divergence of bacterial populations into distinct subpopulations is often the result of ecological isolation. While some studies have suggested the existence of <it>Salmonella enterica </it>subsp. <it>enterica </it>subclades, evidence for these subdivisions has been ambiguous. Here we used a comparative genomics approach to define the population structure of <it>Salmonella enterica </it>subsp. <it>enterica</it>, and identify clade-specific genes that may be the result of ecological specialization.</p> <p>Results</p> <p>Multi-locus sequence analysis (MLSA) and single nucleotide polymorphisms (SNPs) data for 16 newly sequenced and 30 publicly available genomes showed an unambiguous subdivision of <it>S. enterica </it>subsp. <it>enterica </it>into at least two subpopulations, which we refer to as clade A and clade B. Clade B strains contain several clade-specific genes or operons, including a β-glucuronidase operon, a S-fimbrial operon, and cell surface related genes, which strongly suggests niche specialization of this subpopulation. An additional set of 123 isolates was assigned to clades A and B by using qPCR assays targeting subpopulation-specific SNPs and genes of interest. Among 98 serovars examined, approximately 20% belonged to clade B. All clade B isolates contained two pathogenicity related genomic islands, SPI-18 and a cytolethal distending toxin islet; a combination of these two islands was previously thought to be exclusive to serovars Typhi and Paratyphi A. Presence of β-glucuronidase in clade B isolates specifically suggests an adaptation of this clade to the vertebrate gastrointestinal environment.</p> <p>Conclusions</p> <p><it>S. enterica </it>subsp. <it>enterica </it>consists of at least two subpopulations that differ specifically in genes involved in host and tissue tropism, utilization of host specific carbon and nitrogen sources and are therefore likely to differ in ecology and transmission characteristics.</p

The Dynamics of Incomplete Lineage Sorting across the Ancient Adaptive Radiation of Neoavian Birds

The diversification of neoavian birds is one of the most rapid adaptive radiations of extant organisms. Recent whole-genome sequence analyses have much improved the resolution of the neoavian radiation and suggest concurrence with the Cretaceous-Paleogene (K-Pg) boundary, yet the causes of the remaining genome-level irresolvabilities appear unclear. Here we show that genome-level analyses of 2,118 retrotransposon presence/absence markers converge at a largely consistent Neoaves phylogeny and detect a highly differential temporal prevalence of incomplete lineage sorting (ILS), i.e., the persistence of ancestral genetic variation as polymorphisms during speciation events. We found that ILS-derived incongruences are spread over the genome and involve 35% and 34% of the analyzed loci on the autosomes and the Z chromosome, respectively. Surprisingly, Neoaves diversification comprises three adaptive radiations, an initial near-K-Pg super-radiation with highly discordant phylogenetic signals from near-simultaneous speciation events, followed by two post-K-Pg radiations of core landbirds and core waterbirds with much less pronounced ILS. We provide evidence that, given the extreme level of up to 100% ILS per branch in super-radiations, particularly rapid speciation events may neither resemble a fully bifurcating tree nor are they resolvable as such. As a consequence, their complex demographic history is more accurately represented as local networks within a species tree