In cancer, cell migration contributes to the spread of tumor cells resulting in metastasis. Heterogeneity in the migration capacity can produce individual cells with heightened capacity leading to ...invasion and metastasis. Our hypothesis is that cell migration characteristics can divide asymmetrically in mitosis, allowing a subset of cells to have a larger contribution to invasion and metastasis. Therefore, our aim is to elucidate whether sister cells have different migratory capacity and analyze if this difference is defined by mitosis. Through time-lapse videos, we analyzed migration speed, directionality, maximum displacement of each trajectory, and velocity as well as cell area and polarity and then compared the values between mother-daughter cells and between sister cells of three tumor cell lines (A172, MCF7, SCC25) and two normal cell lines (MRC5 and CHO·K1 cells). We observed that daughter cells had a different migratory phenotype compared to their mothers, and one single mitosis is enough for the sisters behave like nonrelated cells. However, mitosis did not influence cell area and polarity dynamics. These findings indicates that migration performance is not heritable, and that asymmetric cell division might have an important impact on cancer invasion and metastasis, by producing cells with different migratory capacity.
•Daughter cells did not conserve migratory phenotype from mother cell.•Sister cells showed changes in migratory behavior.•Asymmetric mitosis affects cell migration of sister cells.•Mitosis did not influence cell area and polarity dynamics between sister cells.
Disease-modifying therapies are needed for Fragile X Syndrome (FXS), as at present there are no effective treatments or cures. Herein, we report on a tetrahydroquinoline-based selective histone ...deacetylase 6 (HDAC6) inhibitor SW-100, its pharmacological and ADMET properties, and its ability to improve upon memory performance in a mouse model of FXS, Fmr1 –/– mice. This small molecule demonstrates good brain penetrance, low-nanomolar potency for the inhibition of HDAC6 (IC50 = 2.3 nM), with at least a thousand-fold selectivity over all other class I, II, and IV HDAC isoforms. Moreover, through its inhibition of the α-tubulin deacetylase domain of HDAC6 (CD2), in cells SW-100 upregulates α-tubulin acetylation with no effect on histone acetylation and selectively restores the impaired acetylated α-tubulin levels in the hippocampus of Fmr1 –/– mice. Lastly, SW-100 ameliorates several memory and learning impairments in Fmr1 –/– mice, thus modeling the intellectual deficiencies associated with FXS, and hence providing a strong rationale for pursuing HDAC6-based therapies for the treatment of this rare disease.
Abstract
Drift experiments are essential to understand stranding patterns and estimate the mortality of beached animals. Most studies do not use telemetry technology due to the high costs of this ...methodology. The objective of this paper is to describe the possibilities of tracking marine tetrapod carcasses with a low‐cost and replicable methodology. The study was carried out on the Southern Subtropical Shelf (~28°–34°S), a highly productive and key ecological region of the southwestern Atlantic Ocean (SWA).
We designed and tested a low‐cost mixed methodology that includes Global Positioning System trackers, passive drifters (reused glass bottles) and Citizen Science (through an instant message platform and email) to track carcasses of marine tetrapods. We conducted four drift experiments during the four seasons of 2019. We released 787 drifters (600 nonbiological and 187 carcasses of seabirds, sea turtles, and cetaceans) at sea, at five equally separated distances (5–25 km) from the coast. Beach surveys and citizen science were implemented to recover the beached drifters.
We recovered 71.83% of non‐biological drifters and 27.27% of carcasses released. We tracked the movements of 38 carcasses (25 sea turtles and 13 cetaceans) with 17 GPS devices. The drifting time, until reaching the beach, ranged from 12 h to 17 days for carcasses and 12 h to 406 days for bottles. Citizen Science was the most important source of recovery of nonbiological drifters, representing 66.67% of the total recovered bottles. For carcasses, active search was the most important recovery source, representing 64.7% of the total carcasses recovered.
Our study contributes with new findings on marine tetrapod drift patterns in the SWA and describes an accessible low‐cost mixed methodology for small and medium‐budget projects that can be replicated in other coastal regions of the world for tracking a wide range of marine tetrapod species.
Resumo
Experimentos de deriva são essenciais para se entender os padrões de encalhe e estimar a mortalidade de animais encalhados. A maioria dos estudos não utilizam telemetria devido aos altos custos desta tecnologia. O objetivo deste trabalho é descrever as possibilidades de rastreamento de carcaças de tetrápodes marinhos com uma metodologia de baixo custo e replicável. O estudo foi conduzido na região subtropical da Plataforma Sul Brasileira (~ 28° ‐ 34° S), considerada uma região ecológica chave e altamente produtiva do Oceano Atlântico Sul Ocidental (ASO).
Nós projetamos e testamos uma metodologia mista de baixo custo, incluindo rastreadores com Sistema de Posicionamento Global (GPS), derivadores passivos (garrafas de vidro reutilizadas), e ciência cidadã (através de plataformas de mensagem instantânea e correio eletrônico) para rastrear carcaças de tetrápodes marinhos. Nós realizamos quatro experimentos de deriva, durante as quatro estações do ano em 2019. Nós soltamos 787 derivadores (600 não‐biológicos e 187 carcaças de aves marinhas, tartarugas marinhas e cetáceos) no mar, em cinco pontos equidistantes 5km um do outro (5 – 25km) a partir da linha de costa. Monitoramentos de praia e ciência cidadã foram utilizados como metodologias para recuperação dos derivadores que encalharam.
Nós recuperamos 71.83% dos derivadores não‐biológicos e 27.27% das carcaças soltas. Nós rastreamos o movimento de 38 carcaças (25 tartarugas marinhas e 13 toninhas, Pontoporia blainvillei) com 17 aparelhos de GPS. O tempo de deriva, até o encalhe, variou de 12h até 17 dias para carcaças e de 12h até 406 dias para as garrafas. A ciência cidadã foi a fonte mais importante de recuperação de derivadores não biológicos, representando 66.67% do total de garrafas recuperadas. Para carcaças, a busca ativa foi a fonte mais importante de recaptura, representando 64.7% do total de carcaças recuperadas.
Nosso estudo contribui com novos achados sobre os padrões de deriva de tetrápodes marinhos no ASO e descreve uma metodologia mista acessível e de baixo custo para projetos com orçamentos pequenos e médios e que pode ser replicada em outras regiões costeiras do mundo para rastreamento de uma ampla gama de espécies de tetrápodes marinhos.
This work presents a prepare method of a bio‐foam constituted by sodium alginate, chitosan (CH), and glyphosate to form a material to be applied in controlled release of herbicide. It was ...investigated the influence of mixture pH on the bio‐foam physicochemical properties. Kinetic studies of glyphosate adsorption and release were performed. The interactions between the polysaccharides and the herbicide were also investigated. The bio‐foams were evaluated for their mechanical and morphological properties. All samples presented swelling degree above 1000%. The bio‐foam prepared at pH 6 presented a higher compression resistance and provided the higher herbicide adsorption. The bio‐foam was able to control the release of glyphosate. The release kinetics reached equilibrium state after 30 days, during which cumulative release was approximately 90%. Confocal microscopy images showed the preferential interaction of glyphosate with the CH molecules in bio‐foam. This work presents a new perspective for polysaccharide systems, enabling new high‐performance agricultural applications.
The Brazilian South coast seasonally hosts numerous marine species, observed particularly during winter months. Some animals, including fur seals, are found dead or debilitated along the shore and ...may harbor potential pathogens within their microbiota. In the present study, a metagenomic approach was performed to evaluate the viral diversity in feces of fur seals found deceased along the coast of the state of Rio Grande do Sul. The fecal virome of two fur seal species was characterized: the South American fur seal (Arctocephalus australis) and the Subantarctic fur seal (Arctocephalus tropicalis). Fecal samples from 10 specimens (A. australis, n = 5; A. tropicalis, n = 5) were collected and viral particles were purified, extracted and amplified with a random PCR. The products were sequenced through Ion Torrent and Illumina platforms and assembled reads were submitted to BLASTx searches. Both viromes were dominated by bacteriophages and included a number of potentially novel virus genomes. Sequences of picobirnaviruses, picornaviruses and a hepevirus-like were identified in A. australis. A rotavirus related to group C, a novel member of the Sakobuvirus and a sapovirus very similar to California sea lion sapovirus 1 were found in A. tropicalis. Additionally, sequences of members of the Anelloviridae and Parvoviridae families were detected in both fur seal species. This is the first metagenomic study to screen the fecal virome of fur seals, contributing to a better understanding of the complexity of the viral community present in the intestinal microbiota of these animals.
Gentamicins are clinically relevant aminoglycoside antibiotics produced by several Micromonospora species. Gentamicins are highly methylated and functionalized molecules, and their biosynthesis ...include glycosyltransferases, dehydratase/oxidoreductases, aminotransferases, and methyltransferases. The biosynthesis of gentamicin A from gentamicin A2 involves three enzymatic steps that modify the hydroxyl group at position 3″ of the unusual garosamine sugar to provide its substitution for an amino group, followed by an N-methylation. The first of these reactions is catalyzed by GenD2, an oxidoreductase from the Gfo/Idh/MocA protein family, which reduces the hydroxyl at the C3″ of gentamicin A to produce 3′′-dehydro-3′′-oxo-gentamicin A2 (DOA2). In this work, we solved the structure of GenD2 in complex with NAD+. Although the structure of GenD2 has a similar fold to other members of the Gfo/Idh/MocA family, this enzyme has several new features, including a 3D-domain swapping of two β-strands that are involved in a novel oligomerization interface for this protein family. In addition, the active site of this enzyme also has several specialties which are possibly involved in the substrate specificity, including a number of aromatic residues and a negatively charged region, which is complementary to the polycationic aminoglycoside-substrate. Therefore, docking simulations provided insights into the recognition of gentamicin A2 and into the catalytic mechanism of GenD2. This is the first report describing the structure of an oxidoreductase involved in aminoglycoside biosynthesis and could open perspectives into producing new aminoglycoside derivatives by protein engineering.
The interaction between the main carrier of endogenous and exogenous compounds in the human bloodstream (human serum albumin, HSA) and a potential anticancer compound (the capsaicin analogue
) was ...investigated by spectroscopic techniques (circular dichroism, steady-state, time-resolved, and synchronous fluorescence), zeta potential, and computational method (molecular docking). Steady-state and time-resolved fluorescence experiments indicated an association in the ground state between HSA:
. The interaction is moderate, spontaneous (Δ
° < 0), and entropically driven (Δ
° = 0.573 ± 0.069 kJ/molK). This association does not perturb significantly the potential surface of the protein, as well as the secondary structure of the albumin and the microenvironment around tyrosine and tryptophan residues. Competitive binding studies indicated Sudlow's site I as the main protein pocket and molecular docking results suggested hydrogen bonding and hydrophobic interactions as the main binding forces.
•This work deals with the acquisition and estimation of otoacoustic emissions (OAE).•It presents a microcontroller-based system for Transient-Evoked OAE acquisition.•It proposes a time–frequency ...binary mask for noise reduction.•Assessment with eight volunteers and one neonate was performed.•The detection time is up to fourteen times faster than commercial equipment.
This work presents the development of a signal acquisition and processing system for the fast detection of Transient-Evoked Otoacoustic Emissions (TEOAE). It was built under IEC 60645-6, IEC 62304, and IEC 82304-1 standards. Hardware and firmware specifications based on a Cortex-M7 microcontroller and an ER-10D acquisition probe are presented. A user interface was designed for parameter configuration and monitoring the detection process in a host personal computer. The signal processing chain is presented, and a time–frequency binary-mask approach is proposed to increase the signal-to-noise ratio, leading to a significant decrease in the average detection time. Results obtained with the implemented prototype for two different detection strategies were compared with those from a commercial equipment. Screening tests were performed with eight volunteers and one neonate with normal hearing. On average, the proposed hardware and associated signal processing methods provided a detection time fourteen times faster than the analyzed commercial system. These results are of special interest to developers of TEOAE screening systems.
New ecosystems are being actively mined for new bioactive compounds. Because of the large amount of unexplored biodiversity, bacteria from marine environments are especially promising. Further, ...host-associated microbes are of special interest because of their low toxicity and compatibility with host health. Here, we identified and characterized biosynthetic gene clusters encoding antimicrobial compounds in host-associated enterococci recovered from fecal samples of wild marine animals remote from human-affected ecosystems. Putative biosynthetic gene clusters in the genomes of 22
strains of marine origin were predicted using antiSMASH5 and Bagel4 bioinformatic software. At least one gene cluster encoding a putative bioactive compound precursor was identified in each genome. Collectively, 73 putative antimicrobial compounds were identified, including 61 bacteriocins (83.56%), 10 terpenes (13.70%), and 2 (2.74%) related to putative nonribosomal peptides (NRPs). Two of the species studied,
and
, are rare causes of human disease and were found to lack any known pathogenic determinants but yet possessed bacteriocin biosynthetic genes, suggesting possible additional utility as probiotics. Wild marine animal-associated enterococci from human-remote ecosystems provide a potentially rich source for new antimicrobial compounds of therapeutic and industrial value and potential probiotic application.
A viscometric study of two polyelectrolytes, chitosan (CH, with 94% deacetylation degree, in a solute-mixture of acetic acid (0.1 mol L−1) and sodium chloride (0.2 mol L−1) and sodium alginate (SA, ...with 62% M-units, in sodium chloride (0.1 mol L−1), was performed at 25 °C. Five different equations were applied to calculate intrinsic viscosity η: Huggins, Kraemer and Schulz-Blaschke (SB) by graphical extrapolation; Solomon-Ciuta, Deb-Chanterjee and again SB, by faster single-point determination. Viscometric constants were calculated employing graphical extrapolation equations. Average molar mass (‾Mv) values were determined by applying the Mark-Houwink-Sakurada equation. For the samples analyzed, Huggins equation was the most suitable to calculate η and‾Mv by graphical extrapolation for chitosan, while Schulz-Blaschke and Solomon-Ciuta were adequate for single-point determinations of sodium alginate. Viscometric constants indicated that the aqueous mixture of acetic acid and sodium chloride is a poor solvent for chitosan, while sodium alginate is well solvated by aqueous sodium chloride.
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