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1.
Violence Against Women ; 29(14): 2699-2729, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37654183

RESUMO

This study sought to understand whether the risk and protective factors associated with current partner violence changed in Vietnam using findings from two comparable surveys conducted in 2010 and 2019. Fifteen (2010) and 17 (2019) factors were significantly associated with violence, and the level of consistency was high-nonpartner sexual violence, respondent and partner prior abuse, men's expressions of masculinity, and indicators of low economic status continue to put women at risk. Gender-transformative approaches that address power inequalities, foster positive parenting, and promote the political and social influence of women are required and should be adapted to the Vietnam context.

2.
Polymers (Basel) ; 15(14)2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37514459

RESUMO

Polymersomes are an exciting modality for drug delivery due to their structural similarity to biological cells and their ability to encapsulate both hydrophilic and hydrophobic drugs. In this regard, the current work aimed to develop multifunctional polymersomes, integrating dye (with hydrophobic Nile red and hydrophilic sulfo-cyanine5-NHS ester as model drugs) encapsulation, stimulus responsiveness, and surface-ligand modifications. Polymersomes constituting poly(N-2-hydroxypropylmethacrylamide)-b-poly(N-(2-(methylthio)ethyl)acrylamide) (PHPMAm-b-PMTEAM) are prepared by aqueous dispersion RAFT-mediated polymerization-induced self-assembly (PISA). The hydrophilic block lengths have an effect on the obtained morphologies, with short chain P(HPMAm)16 affording spheres and long chain P(HPMAm)43 yielding vesicles. This further induces different responses to H2O2, with spheres fragmenting and vesicles aggregating. Folic acid (FA) is successfully conjugated to the P(HPMAm)43, which self-assembles into FA-functionalized P(HPMAm)43-b-P(MTEAM)300 polymersomes. The FA-functionalized P(HPMAm)43-b-P(MTEAM)300 polymersomes entrap both hydrophobic Nile red (NR) and hydrophilic Cy5 dye. The NR-loaded FA-linked polymersomes exhibit a controlled release of the encapsulated NR dye when exposed to 10 mM H2O2. All the polymersomes formed are stable in human plasma and well-tolerated in MCF-7 breast cancer cells. These preliminary results demonstrate that, with simple and scalable chemistry, PISA offers access to different shapes and opens up the possibility of the one-pot synthesis of multicompartmental and responsive polymersomes.

3.
J Colloid Interface Sci ; 641: 1043-1057, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36996683

RESUMO

Sustainably derived poly(glycerol adipate) (PGA) has been deemed to deliver all the desirable features expected in a polymeric scaffold for drug-delivery, including biodegradability, biocompatibility, self-assembly into nanoparticles (NPs) and a functionalisable pendant group. Despite showing these advantages over commercial alkyl polyesters, PGA suffers from a series of key drawbacks caused by poor amphiphilic balance. This leads to weak drug-polymer interactions and subsequent low drug-loading in NPs, as well as low NPs stability. To overcome this, in the present work, we applied a more significant variation of the polyester backbone while maintaining mild and sustainable polymerisation conditions. We have investigated the effect of the variation of both hydrophilic and hydrophobic segments upon physical properties and drug interactions as well as self-assembly and NPs stability. For the first time we have replaced glycerol with the more hydrophilic diglycerol, as well as adjusting the final amphiphilic balance of the polyester repetitive units by incorporating the more hydrophobic 1,6-n-hexanediol (Hex). The properties of the novel poly(diglycerol adipate) (PDGA) variants have been compared against known polyglycerol-based polyesters. Interestingly, while the bare PDGA showed improved water solubility and diminished self-assembling ability, the Hex variation demonstrated enhanced features as a nanocarrier. In this regard, PDGAHex NPs were tested for their stability in different environments and for their ability to encode enhanced drug loading. Moreover, the novel materials have shown good biocompatibility in both in vitro and in vivo (whole organism) experiments.


Assuntos
Glicerol , Nanopartículas , Sistemas de Liberação de Medicamentos , Poliésteres/química , Preparações Farmacêuticas , Adipatos/química , Nanopartículas/química , Portadores de Fármacos/química
4.
Sci Data ; 9(1): 429, 2022 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-35858929

RESUMO

Most of the existing chest X-ray datasets include labels from a list of findings without specifying their locations on the radiographs. This limits the development of machine learning algorithms for the detection and localization of chest abnormalities. In this work, we describe a dataset of more than 100,000 chest X-ray scans that were retrospectively collected from two major hospitals in Vietnam. Out of this raw data, we release 18,000 images that were manually annotated by a total of 17 experienced radiologists with 22 local labels of rectangles surrounding abnormalities and 6 global labels of suspected diseases. The released dataset is divided into a training set of 15,000 and a test set of 3,000. Each scan in the training set was independently labeled by 3 radiologists, while each scan in the test set was labeled by the consensus of 5 radiologists. We designed and built a labeling platform for DICOM images to facilitate these annotation procedures. All images are made publicly available in DICOM format along with the labels of both the training set and the test set.


Assuntos
Algoritmos , Radiografia Pulmonar de Massa , Humanos , Radiografia , Radiologistas , Estudos Retrospectivos
5.
J Colloid Interface Sci ; 618: 173-184, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35338924

RESUMO

HYPOTHESIS: We describe the possibility of using the same block copolymer carriers prepared by PISA for in situ drug encapsulation or drug conjugation. EXPERIMENTS: Block copolymers containing poly((ethylene glycol) methacrylate)-co-poly(pentafluorophenyl methacrylate)-b-poly(hydroxypropyl methacrylate) (P((PEGMA-co-PFBMA)-b-PHPMA)) were synthesized at 10 wt% using PISA. The first approach involved in situ Doxorubicin (DOX) loading during PISA, while the second exhibited surface functionalization of PISA-made vesicles with dual drug therapies, N-acetyl cysteine (NAC) and DOX using para-fluoro-thiol reaction (PFTR) and carbodiimide chemistry, respectively. Cytotoxicity, cell uptake, and cell apoptosis were assessed on MDA-MB-231 cell lines. FINDINGS: P((PEGMA-co-PFBMA)-b-PHPMA) nanocarriers were prepared, showing size and shape transformations from spheres, cylinders to raspberry-forming vesicles. DOX was readily loaded into NPs during PISA with relatively high encapsulation efficiency of 70 %, whereas the plain PISA-made vesicles could be functionalized with NAC and DOX at high yields. DOX-free NPs showed biocompatibility, whilst DOX-conjugated NPs imparted a concentration-dependent cytotoxicity, as well as an enhanced cell uptake compared to free DOX. The results demonstrated that the same PISA-derived self-assemblies enabled either in situ drug encapsulation, or post-polymerization surface engineering with useful functionalities upon tuning the macro-CTA block, thus holding promises for future drug delivery and biomedical applications.


Assuntos
Nanopartículas , Neoplasias , Doxorrubicina/metabolismo , Doxorrubicina/farmacologia , Portadores de Fármacos , Humanos , Metacrilatos , Micelas , Polimerização , Polímeros
6.
Biomacromolecules ; 23(3): 1221-1231, 2022 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-34991313

RESUMO

Sequence-regulating polyhydroxyalkanoate synthase PhaCAR is a chimeric enzyme comprising PhaCs from Aeromonas caviae and Ralstonia eutropha (Cupriavidus necator). It spontaneously synthesizes a short-chain-length (SCL, ≤C5) block copolymer poly(2-hydroxybutyrate)-b-poly(3-hydroxybutyrate) [P(2HB)-b-P(3HB)] from a mixture of monomer substrates. In this study, directed evolution of PhaCAR was performed to increase its activity toward a medium-chain-length (MCL, C6-12) monomer, 3-hydroxyhexanoyl (3HHx)-coenzyme A (CoA). Random mutagenesis and selection based on P(3HB-co-3HHx) production in Escherichia coli found that beneficial mutations N149D and F314L increase the 3HHx fraction. The site-directed saturation mutagenesis at position 314, which is adjacent to the catalytic center C315, demonstrated that F314H synthesizes the P(3HHx) homopolymer. The F314H mutant exhibited increased activity toward 3HHx-CoA compared with the parent enzyme, whereas the activity toward 3HB-CoA decreased. The predicted tertiary structure of PhaCAR by AlphaFold2 provided insight into the mechanism of the beneficial mutations. In addition, this finding enabled the synthesis of a new PHA block copolymer, P(3HHx)-b-P(2HB). Solvent fractionation indicated the presence of a covalent linkage between the polymer segments. This novel MCL-SCL block copolymer considerably expands the range of the molecular design of PHA block copolymers.


Assuntos
Cupriavidus necator , Aciltransferases/genética , Coenzima A , Meios de Cultura , Cupriavidus necator/genética , Escherichia coli/genética , Polímeros
7.
Dev Psychopathol ; 33(2): 409-420, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32935656

RESUMO

This article provides an overview of selected ongoing international efforts that have been inspired by Edward Zigler's vision to improve programs and policies for young children and families in the United States. The efforts presented are in close alignment with three strategies articulated by Edward Zigler: (a) conduct research that will inform policy advocacy; (b) design, implement, and revise quality early childhood development (ECD) programs; and (c) invest in building the next generation of scholars and advocates in child development. The intergenerational legacy left by Edward Zigler has had an impact on young children not only in the United States, but also across the globe. More needs to be done. We need to work together with a full commitment to ensure the optimal development of each child.


Assuntos
Desenvolvimento Infantil , Família , Criança , Pré-Escolar , Humanos , Estados Unidos
8.
Biomater Sci ; 9(1): 38-50, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33179646

RESUMO

Stimuli-responsive amphiphilic block copolymers have emerged as promising nanocarriers for enhancing site-specific and on-demand drug release in response to a range of stimuli such as pH, the presence of redox agents, and temperature. The formulation of amphiphilic block copolymers into polymeric drug-loaded nanoparticles is typically achieved by various methods (e.g. oil-in-water emulsion solvent evaporation, solid dispersion, microphase separation, dialysis or microfluidic separation). Despite much progress that has been made, there remain many challenges to overcome to produce reliable polymeric systems. The main drawbacks of the above methods are that they produce very low solid contents (<1 wt%) and involve multiple-step procedures, thus limiting their scope. Recently, a new self-assembly methodology, polymerisation-induced self-assembly (PISA), has shown great promise in the production of polymer-derived particles using a straightforward one-pot approach, whilst facilitating high yield, scalability, and cost-effectiveness for pharmaceutical industry protocols. We therefore focus this review primarily on the most recent studies involved in the design and preparation of PISA-generated nano-objects which are responsive to specific stimuli, thus providing insight into how PISA may become an effective formulation strategy for the preparation of precisely tailored drug delivery systems and biomaterials, while some of the current challenges and limitations are also critically discussed.


Assuntos
Nanopartículas , Polímeros , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Polimerização
9.
Front Microbiol ; 7: 1779, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27899916

RESUMO

Lipolytic enzymes that retain high levels of catalytic activity when exposed to a variety of denaturing conditions are of high importance for a number of biotechnological applications. In this study, we aimed to identify new lipolytic enzymes, which are highly resistant to prolonged exposure to elevated temperatures. To achieve this, we searched for genes encoding for such proteins in the genomes of a microbial consortium residing in a hot spring located in China. After performing functional genomic screening on a bacterium of the genus Dictyoglomus, which was isolated from this hot spring following in situ enrichment, we identified a new esterolytic enzyme, termed EstDZ3. Detailed biochemical characterization of the recombinant enzyme, revealed that it constitutes a slightly alkalophilic and highly active esterase against esters of fatty acids with short to medium chain lengths. Importantly, EstDZ3 exhibits remarkable thermostability, as it retains high levels of catalytic activity after exposure to temperatures as high as 95°C for several hours. Furthermore, it exhibits very good stability against exposure to high concentrations of a variety of organic solvents. Interestingly, EstDZ3 was found to have very little similarity to previously characterized esterolytic enzymes. Computational modeling of the three-dimensional structure of this new enzyme predicted that it exhibits a typical α/ß hydrolase fold that seems to include a "subdomain insertion", which is similar to the one present in its closest homolog of known function and structure, the cinnamoyl esterase Lj0536 from Lactobacillus johnsonii. As it was found in the case of Lj0536, this structural feature is expected to be an important determinant of the catalytic properties of EstDZ3. The high levels of esterolytic activity of EstDZ3, combined with its remarkable thermostability and good stability against a range of organic solvents and other denaturing agents, render this new enzyme a candidate biocatalyst for high-temperature biotechnological applications.

10.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 8): m893, 2010 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-21588137

RESUMO

The title compound, [Na(CF(3)O(3)S)(C(12)H(24)O(6))], features a sodium cation that is coordinated by eight O atoms in an irregular hexa-gonal bipyramidal environment. The equatorial positions are occupied by the six O atoms of an 18-crown-6 ether ring. In the axial positions, there is one O atom of a trifluoro-methane-sulfonate anion and an ether O atom of a symmetry-equivalent crown ether ring. In this way, centrosymmetric dimers are formed.

11.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 8): m928, 2010 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-21588161

RESUMO

The asymmetric unit of the title compound, [K(C(5)HF(6)N(2))(H(2)O)(2)](n), is composed of two 3,5-bis-(trifluoro-meth-yl)pyrazol-ide anions, two potassium cations and four water mol-ecules. The water mol-ecules and 3,5-bis-(trifluoro-meth-yl)pyrazolide anions act as bridges between the potassium cations. Each potassium cation is surrounded by four O atoms [K-O = 2.705 (3)-2.767 (3) Å] and four F atoms [K-F = 2.870 (7)-3.215 (13) Å]. The water mol-ecules and the 3,5-bis-(trifluoro-meth-yl)pyrazolide anions are connected by O-H⋯N hydrogen bonds, forming layers in the ab plane. All -CF(3) groups show rotational disorder between two orientations each.

12.
Mol Microbiol ; 72(1): 259-72, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19239620

RESUMO

Clusters of regularly interspaced short palindromic repeats (CRISPRs) of Sulfolobus fall into three main families based on their repeats, leader regions, associated cas genes and putative recognition sequences on viruses and plasmids. Spacer sequence matches to different viruses and plasmids of the Sulfolobales revealed some bias particularly for family III CRISPRs. Transcription occurs on both strands of the five repeat-clusters of Sulfolobus acidocaldarius and a repeat-cluster of the conjugative plasmid pKEF9. Leader strand transcripts cover whole repeat-clusters and are processed mainly from the 3'-end, within repeats, yielding heterogeneous 40-45 nt spacer RNAs. Processing of the pKEF9 leader transcript occurred partially in spacers, and was incomplete, probably reflecting defective repeat recognition by host enzymes. A similar level of transcripts was generated from complementary strands of each chromosomal repeat-cluster and they were processed to yield discrete approximately 55 nt spacer RNAs. Analysis of the partially identical repeat-clusters of Sulfolobus solfataricus strains P1 and P2 revealed that spacer-repeat units are added upstream only when a leader and certain cas genes are linked. Downstream ends of the repeat-clusters are conserved such that deletions and recombination events occur internally.


Assuntos
Sequências Repetidas Invertidas , Família Multigênica , Sulfolobus/genética , Transcrição Gênica , Regiões 5' não Traduzidas , Filogenia , RNA Arqueal/genética , Alinhamento de Sequência , Análise de Sequência de DNA , Sítio de Iniciação de Transcrição
13.
J Bacteriol ; 190(20): 6837-45, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18723627

RESUMO

A newly characterized archaeal rudivirus Stygiolobus rod-shaped virus (SRV), which infects a hyperthermophilic Stygiolobus species, was isolated from a hot spring in the Azores, Portugal. Its virions are rod-shaped, 702 (+/- 50) by 22 (+/- 3) nm in size, and nonenveloped and carry three tail fibers at each terminus. The linear double-stranded DNA genome contains 28,096 bp and an inverted terminal repeat of 1,030 bp. The SRV shows morphological and genomic similarities to the other characterized rudiviruses Sulfolobus rod-shaped virus 1 (SIRV1), SIRV2, and Acidianus rod-shaped virus 1, isolated from hot acidic springs of Iceland and Italy. The single major rudiviral structural protein is shown to generate long tubular structures in vitro of similar dimensions to those of the virion, and we estimate that the virion constitutes a single, superhelical, double-stranded DNA embedded into such a protein structure. Three additional minor conserved structural proteins are also identified. Ubiquitous rudiviral proteins with assigned functions include glycosyl transferases and a S-adenosylmethionine-dependent methyltransferase, as well as a Holliday junction resolvase, a transcriptionally coupled helicase and nuclease implicated in DNA replication. Analysis of matches between known crenarchaeal chromosomal CRISPR spacer sequences, implicated in a viral defense system, and rudiviral genomes revealed that about 10% of the 3,042 unique acidothermophile spacers yield significant matches to rudiviral genomes, with a bias to highly conserved protein genes, consistent with the widespread presence of rudiviruses in hot acidophilic environments. We propose that the 12-bp indels which are commonly found in conserved rudiviral protein genes may be generated as a reaction to the presence of the host CRISPR defense system.


Assuntos
Rudiviridae/crescimento & desenvolvimento , Rudiviridae/genética , Sulfolobaceae/fisiologia , Sulfolobaceae/virologia , Açores , Cromossomos de Archaea , DNA Viral/química , DNA Viral/genética , Ordem dos Genes , Genes Virais , Fontes Termais , Mutação INDEL , Substâncias Macromoleculares , Microscopia Eletrônica de Transmissão , Modelos Moleculares , Dados de Sequência Molecular , Rudiviridae/isolamento & purificação , Rudiviridae/ultraestrutura , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Sintenia , Proteínas não Estruturais Virais/genética , Proteínas Estruturais Virais/química , Proteínas Estruturais Virais/genética , Vírion/ultraestrutura
14.
Mol Microbiol ; 54(2): 366-75, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15469509

RESUMO

The DNA rudivirus SIRV1 of the hyperthermophilic archaeon Sulfolobus shows exceptional properties. Viral isolates invariably contain a population of variants with different but closely related genomes. Upon propagation in a given host strain, one or more genomes dominate in the viral population. However, upon passage into a new host strain the viral population undergoes changes and other dominant variants are selected. Sequencing and analysis of the variant genomes revealed that major differences occur in gene order, gene size and gene content at localized genomic sites. A previously unknown mechanism of genomic rearrangement involving putative 12 bp archaeal introns appears to facilitate alteration of the variant genomes. Inter-genomic recombination between the different variants also occurs. The variant genomes exhibit signature tetranucleotide sequences near their putative sites for replication initiation.


Assuntos
DNA Viral , Variação Genética , Rudiviridae/genética , Sulfolobus/genética , Sulfolobus/virologia , Sequência de Bases , Genoma Viral , Íntrons , Conformação de Ácido Nucleico , Fases de Leitura Aberta , Rudiviridae/metabolismo
15.
Res Microbiol ; 154(4): 295-302, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12798235

RESUMO

The fusellovirus SSV2 from an Icelandic Sulfolobus strain was isolated, characterized and its complete genomic sequence determined. SSV2 is very similar in morphology, replication, genome size and number of open reading frames (ORFs) to the type virus of the family, SSV1 from Japan, except in its high level of uninduced virus production. The nucleotide sequences are, however, only 55% identical to each other, much less than related bacteriophage, related animal viruses and the rudiviruses of Sulfolobus, SIRV1 and SIRV2. Nevertheless the genome architecture is very similar between the two viruses, indicating that despite this genomic dissimilarity the virus genomes are mostly homologous. Unlike SSV1, the sequence of SSV2 indicates integration into a glycyl tRNA gene and is completely missing a DNA packaging gene. There is a unique, perfectly tandemly directly repeated sequence of 62 nucleotides in SSV2 that has no similarity to known sequences or structures. By comparison to the SSV2 genome, an integrated partial fusellovirus genome was found in the Sulfolobus solfataricus P2 genome further confirming the dynamism of the Sulfolobus genome. Clustering of cysteine codon containing ORFs both in SSV1 and SSV2 indicates that these Fuselloviridae arose from a genome fusion event.


Assuntos
Fuselloviridae , Sulfolobus/virologia , Fuselloviridae/química , Fuselloviridae/genética , Fuselloviridae/isolamento & purificação , Fuselloviridae/ultraestrutura , Genoma Viral , Genômica , Lisogenia/genética , Fases de Leitura Aberta , RNA de Transferência/genética , Homologia de Sequência , Proteínas Virais/química , Proteínas Virais/genética
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