Assembling large, complex environmental metagenomes

The large volumes of sequencing data required to sample complex environments deeply pose new challenges to sequence analysis approaches. De novo metagenomic assembly effectively reduces the total amount of data to be analyzed but requires significant computational resources. We apply two pre-assembly filtering approaches, digital normalization and partitioning, to make large metagenome assemblies more comput\ ationaly tractable. Using a human gut mock community dataset, we demonstrate that these methods result in assemblies nearly identical to assemblies from unprocessed data. We then assemble two large soil metagenomes from matched Iowa corn and native prairie soils. The predicted functional content and phylogenetic origin of the assembled contigs indicate significant taxonomic differences despite similar function. The assembly strategies presented are generic and can be extended to any metagenome; full source code is freely available under a BSD license.Comment: Includes supporting informatio

New perspectives in cancer biology from a study of canonical and non-canonical functions of base excision repair proteins with a focus on early steps

Alterations of DNA repair enzymes and consequential triggering of aberrant DNA damage response (DDR) pathways are thought to play a pivotal role in genomic instabilities associated with cancer development, and are further thought to be important predictive biomarkers for therapy using the synthetic lethality paradigm. However, novel unpredicted perspectives are emerging from the identification of several non-canonical roles of DNA repair enzymes, particularly in gene expression regulation, by different molecular mechanisms, such as (i) non-coding RNA regulation of tumour suppressors, (ii) epigenetic and transcriptional regulation of genes involved in genotoxic responses and (iii) paracrine effects of secreted DNA repair enzymes triggering the cell senescence phenotype. The base excision repair (BER) pathway, canonically involved in the repair of non-distorting DNA lesions generated by oxidative stress, ionising radiation, alkylation damage and spontaneous or enzymatic deamination of nucleotide bases, represents a paradigm for the multifaceted roles of complex DDR in human cells. This review will focus on what is known about the canonical and non-canonical functions of BER enzymes related to cancer development, highlighting novel opportunities to understand the biology of cancer and representing future perspectives for designing new anticancer strategies. We will specifically focus on APE1 as an example of a pleiotropic and multifunctional BER protein

Follicular development, plasma Inhibin-A and Estradiol-17-beta concentrations in Buffalo cows during different treatment schedules for MOET programs

Buffalo cows were submitted to three superovulatory treatments. T1 (n = 7): PRID for 10 days (d0-d9) plus decreasing doses of 500 IU FSH/LH (12 h-intervals d7‑d10); T2 (n = 8): PRID for 11 d (d0-d10) plus 2000 IU PMSG at d7; T3 (n = 9): PRID for 11 d plus 2000 IU PMSG at d7 and decreasing doses of 175 IU FSH/LH (12 h-intervals d10‑ d11). Overall plasma inhibin‑A (In-A) concentrations correlated with large follicles (LF, diameter >6mm, R=0.83, P10 mm at d12- 13 (T1=5.0+/-1.4, T2=1.2+/-0.9, T3=8.3+/-2.3). In-A concentrations significantly rised at d11-13 of T1 and T3. In-A seems a good indicator of the follicular development during superovulation in buffalo cows, while E2 is not. Furthermore T3 was followed by better ovarian follicular responses

Hybrid stars with sequential phase transitions: the emergence of the g2_2 mode

Neutron stars are the densest objects in the Universe, with $M \sim 1.4 M_{\odot}$ and $R \sim 12$ km, and the equation of state associated to their internal composition is still unknown. The extreme conditions to which matter is subjected inside neutron stars could lead to a phase transition in their inner cores, giving rise to a hybrid compact object. The observation of $2M_{\odot}$ binary pulsars (PSR~J1614-2230, PSR~J0343$+$0432 and PSR~J0740$+$6620) strongly constraints theoretical models of the equation of state. Moreover, the detection of gravitational waves emitted during the binary neutron star merger, GW170817, and its electromagnetic counterpart, GRB170817A, impose additional constraints on the tidal deformability. In this work, we investigate hybrid stars with sequential phase transitions hadron-quark-quark in their cores. We assume that both phase transitions are sharp and analyse the rapid and slow phase conversion scenarios. For the outer core, we use modern hadronic equations of state. For the inner core we employ the constant speed of sound parametrization for quark matter. We analyze more than 3000 hybrid equations of state, taking into account the recent observational constraints from neutron stars. The effects of hadron-quark-quark phase transitions on the normal oscillation modes $f$ and $g$, are studied under the Cowling relativistic approximation. Our results show that, in the slow conversion regime, a second quark-quark phase transition gives rise to a new $g_2$~mode. We discuss the observational implications of our results associated to the gravitational waves detection and the possibility of detecting hints of sequential phase transitions and the associated $g_2$~mode.Comment: 24 pages, 9 figure

Enzymatically active apurinic/apyrimidinic endodeoxyribonuclease 1 is released by mammalian cells through exosomes

The apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1), the main AP-endonuclease of the DNA base excision repair pathway, is a key molecule of interest to researchers due to its unsuspected roles in different nonrepair activities, such as: I) adaptive cell response to genotoxic stress, ii) regulation of gene expression, and iii) processing of microRNAs, which make it an excellent drug target for cancer treatment. We and others recently demonstrated that APE1 can be secreted in the extracellular environment and that serum APE1 may represent a novel prognostic biomarker in hepatocellular and non-smallcell lung cancers. However, the mechanism by which APE1 is released extracellularly was not described before. Here, using three different approaches for exosomes isolation: Commercial kit, nickel-based isolation, and ultracentrifugation methods and various mammalian cell lines, we elucidated the mechanisms responsible for APE1 secretion. We demonstrated that APE1 p37 and p33 forms are actively secreted through extracellular vesicles (EVs), including exosomes from different mammalian cell lines. We then observed that APE1 p33 form is generated by proteasomal-mediated degradation and is enzymatically active in EVs. Finally, we revealed that the p33 form of APE1 accumulates in EVs upon genotoxic treatment by cisplatin and doxorubicin, compounds commonly found in chemotherapy pharmacological treatments. Taken together, these findings provide for the first time evidence that a functional Base Excision Repair protein is delivered through exosomes in response to genotoxic stresses, shedding new light into the complex noncanonical biological functions of APE1 and opening new intriguing perspectives on its role in cancer biology

Common spatiotemporal processing of visual features shapes object representation

none10Biological vision relies on representations of the physical world at different levels of complexity. Relevant features span from simple low-level properties, as contrast and spatial frequencies, to object-based attributes, as shape and category. However, how these features are integrated into coherent percepts is still debated. Moreover, these dimensions often share common biases: for instance, stimuli from the same category (e.g., tools) may have similar shapes. Here, using magnetoencephalography, we revealed the temporal dynamics of feature processing in human subjects attending to objects from six semantic categories. By employing Relative Weights Analysis, we mitigated collinearity between model-based descriptions of stimuli and showed that low-level properties (contrast and spatial frequencies), shape (medial-axis) and category are represented within the same spatial locations early in time: 100-150 ms after stimulus onset. This fast and overlapping processing may result from independent parallel computations, with categorical representation emerging later than the onset of low-level feature processing, yet before shape coding. Categorical information is represented both before and after shape, suggesting a role for this feature in the refinement of categorical matching.nonePapale, Paolo; Betta, Monica; Handjaras, Giacomo; Malfatti, Giulia; Cecchetti, Luca; Rampinini, Alessandra; Pietrini, Pietro; Ricciardi, Emiliano; Turella, Luca; Leo, AndreaPapale, Paolo; Betta, Monica; Handjaras, Giacomo; Malfatti, Giulia; Cecchetti, Luca; Rampinini, Alessandra; Pietrini, Pietro; Ricciardi, Emiliano; Turella, Luca; Leo, Andre

Effective SARS-CoV-2 antiviral activity of hyperbranched polylysine nanopolymers

The coronavirus pandemic (COVID-19) had spread rapidly since December 2019, when it was first identified in Wuhan, China. As of April 2021, more than 130 million cases have been confirmed, with more than 3 million deaths, making it one of the deadliest pandemics in history. Different approaches must be put in place to confront a new pandemic: community-based behaviours (i.e., isolation and social distancing), antiviral treatments, and vaccines. Although behaviour-based actions have produced significant benefits and several efficacious vaccines are now available, there is still an urgent need for treatment options. Remdesivir represents the first antiviral drug approved by the Food and Drug Administration for COVID-19 but has several limitations in terms of safety and treatment benefits. There is still a strong request for other effective, safe, and broad-spectrum antiviral systems in light of future emergent coronaviruses. Here, we describe a polymeric nanomaterial derived from l-lysine, with an antiviral activity against SARS-CoV-2 associated with a good safety profile in vitro. Nanoparticles of hyperbranched polylysine, synthesized by l-lysine's thermal polymerization catalyzed by boric acid, effectively inhibit the SARS-CoV-2 replication. The virucidal activity is associated with the charge and dimension of the nanomaterial, favouring the electrostatic interaction with the viral surface being only slightly larger than the virions' dimensions. Low-cost production and easiness of synthesis strongly support the further development of such innovative nanomaterials as a tool for potential treatments of COVID-19 and, in general, as broad-spectrum antivirals. This journal i

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bitstream/item/133214/1/ID-43372-2014-TCC-MiniColetorDados.pdfTCC (Bacharelado em Ciência da Computação) - Universidade de Passo Fundo, Passo Fundo