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1.
Acta Haematol ; : 1-10, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861934

RESUMO

INTRODUCTION: Promotion of self-efficacy can enhance engagement with health care and treatment adherence in patients with cancer. We report the outcomes of a pilot trial of a digital health coach intervention in patients with leukemia with the aim of improving self-efficacy. METHODS: Adult patients with newly diagnosed acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) were randomized 1:1 to a digital health coach intervention or standard of care. The primary outcome of self-efficacy was measured by the Cancer Behavior Inventory (CBI) score. RESULTS: A total of 147 patients (37 AML, 110 CLL) were enrolled from July 2020 to December 2022. In the AML cohort, there was a mean increase in CBI score of 7.03 in the digital health coaching arm compared to a mean decrease of -3.57 in the control arm at 30 days (p = 0.219). There were no significant associations between the intervention and other patient-reported outcomes for patients with CLL. CONCLUSION: There were numerical, but not statistically significant increases in self-efficacy metrics in AML patients who received digital health coaching. Although this trial was underpowered due to enrollment limitations during a pandemic, digital health coaching may provide benefit to patients with hematologic malignancy and warrants further investigation.

2.
JAMA ; 330(22): 2200-2208, 2023 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-37943553

RESUMO

Importance: In the US, the prevalence of hepatitis C virus (HCV) is 1.8% among people who are Black and 0.8% among people who are not Black. Mortality rates due to HCV are 5.01/100 000 among people who are Black and 2.98/100 000 among people who are White. Observations: While people of all races and ethnicities experienced increased rates of incident HCV between 2015 and 2021, Black individuals experienced the largest percentage increase of 0.3 to 1.4/100 000 (367%) compared with 1.8 to 2.7/100 000 among American Indian/Alaska Native (50%), 0.3 to 0.9/100 000 among Hispanic (200%), and 0.9 to 1.6/100 000 among White (78%) populations. Among 47 687 persons diagnosed with HCV in 2019-2020, including 37 877 (79%) covered by Medicaid (7666 Black and 24 374 White individuals), 23.5% of Black people and 23.7% of White people with Medicaid insurance initiated HCV treatment. Strategies to increase HCV screening include electronic health record prompts for universal HCV screening, which increased screening tests from 2052/month to 4169/month in an outpatient setting. Awareness of HCV status can be increased through point-of-care testing in community-based settings, which was associated with increased likelihood of receiving HCV test results compared with referral for testing off-site (69% on-site vs 19% off-site, P < .001). Access to HCV care can be facilitated by patient navigation, in which an individual is assigned to work with a patient to help them access care and treatments; this was associated with greater likelihood of HCV care access (odds ratio, 3.7 [95% CI, 2.9-4.8]) and treatment initiation within 6 months (odds ratio, 3.2 [95% CI, 2.3-4.2]) in a public health system providing health care to individuals regardless of their insurance status or ability to pay compared with usual care. Eliminating Medicaid's HCV treatment restrictions, including removal of a requirement for advanced fibrosis or a specialist prescriber, was associated with increased treatment rates from 2.4 persons per month to 72.3 persons per month in a retrospective study of 10 336 adults with HCV with no significant difference by race (526/1388 [37.8%] for Black vs 2706/8277 [32.6%] for White patients; adjusted odds ratio, 1.02 [95% CI, 0.8-1.3]). Conclusions and Relevance: In the US, the prevalence of HCV is higher in people who are Black than in people who are not Black. Point-of-care HCV tests, patient navigation, electronic health record prompts, and unrestricted access to HCV treatment in community-based settings have potential to increase diagnosis and treatment of HCV and improve outcomes in people who are Black.


Assuntos
Hepacivirus , Hepatite C , Adulto , Estados Unidos/epidemiologia , Humanos , Estudos Retrospectivos , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Etnicidade , População Negra
3.
J Org Chem ; 87(1): 258-270, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34913698

RESUMO

The (+) and (-) enantiomers of a new turn-inducing cyclopropyl dipeptide mimic have been synthesized and evaluated. The mimic derives its turn-inducing capabilities solely from the cyclopropyl group and without the conformational biasing that would be provided by side-chain substituents. The mimic and peptide-mimic hybrids prepared from it have been studied using a combination of spectroscopic techniques (NMR, IR, and CD). The dipeptide mimic itself displays intramolecular hydrogen bonding in organic solvents, which differs from that observed in natural peptide turns. In contrast, more elaborate peptide-mimic hybrids exhibit hydrogen bonding characteristics that vary with solvent but are consistent with structures found in the tetrapeptide portion (i → i + 3) of a native ß-turn.


Assuntos
Dipeptídeos , Peptídeos , Ligação de Hidrogênio , Conformação Molecular , Estereoisomerismo
4.
Eur Biophys J ; 50(3-4): 411-427, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33881594

RESUMO

Microscale thermophoresis (MST), and the closely related Temperature Related Intensity Change (TRIC), are synonyms for a recently developed measurement technique in the field of biophysics to quantify biomolecular interactions, using the (capillary-based) NanoTemper Monolith and (multiwell plate-based) Dianthus instruments. Although this technique has been extensively used within the scientific community due to its low sample consumption, ease of use, and ubiquitous applicability, MST/TRIC has not enjoyed the unambiguous acceptance from biophysicists afforded to other biophysical techniques like isothermal titration calorimetry (ITC) or surface plasmon resonance (SPR). This might be attributed to several facts, e.g., that various (not fully understood) effects are contributing to the signal, that the technique is licensed to only a single instrument developer, NanoTemper Technology, and that its reliability and reproducibility have never been tested independently and systematically. Thus, a working group of ARBRE-MOBIEU has set up a benchmark study on MST/TRIC to assess this technique as a method to characterize biomolecular interactions. Here we present the results of this study involving 32 scientific groups within Europe and two groups from the US, carrying out experiments on 40 Monolith instruments, employing a standard operation procedure and centrally prepared samples. A protein-small molecule interaction, a newly developed protein-protein interaction system and a pure dye were used as test systems. We characterized the instrument properties and evaluated instrument performance, reproducibility, the effect of different analysis tools, the influence of the experimenter during data analysis, and thus the overall reliability of this method.


Assuntos
Benchmarking , Laboratórios , Calorimetria , Reprodutibilidade dos Testes , Temperatura
5.
AIDS Behav ; 24(6): 1776-1783, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31748939

RESUMO

Adults entering pre-trial detention who inject drugs are at high risk for acquiring HIV/AIDS. In the current study, we examined pre-incarceration HIV risk behaviors among 114 people with opioid use disorder who inject drugs. Participants were recruited from the Baltimore City Detention Center as part of a randomized controlled trial of pre-release methadone treatment. Using latent class analysis, we found three separate latent classes, which we identified as the sex exchange class (14.2%), drug equipment sharing class (36.8%) and lower risk class (49.0%). Women in the sex exchange class (n = 16) reported having multiple male partners and selling sex for money or drugs; however, this group also reported more consistent condom use and less frequent injection drug and equipment sharing than participants in the drug equipment sharing class. Our findings highlight distinct profiles of jail detainees with OUD based on their risks for HIV, and could inform more targeted interventions for each group.Clinical Trials Registration: Clinicaltrials.gov NCT02334215.


Assuntos
Infecções por HIV/prevenção & controle , Transtornos Relacionados ao Uso de Opioides/psicologia , Assunção de Riscos , Sexo Seguro , Parceiros Sexuais , Adulto , Baltimore , Preservativos , Direito Penal , Feminino , Humanos , Análise de Classes Latentes , Masculino , Pessoa de Meia-Idade , Prisões , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
6.
J Vis Commun Med ; 43(4): 184-189, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32967479

RESUMO

This article provides an overview of how long COVID-19 (SARS-CoV-2) survives on the built environment, and reviews currently available resources to provide recommendations on effective decontamination of photographic equipment based within a secondary care setting.


Assuntos
Betacoronavirus/isolamento & purificação , Ambiente Construído , Infecções por Coronavirus/prevenção & controle , Descontaminação/métodos , Pandemias/prevenção & controle , Fotografação/instrumentação , Pneumonia Viral/prevenção & controle , COVID-19 , Humanos , SARS-CoV-2
7.
Chemistry ; 25(33): 7881-7887, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-30945773

RESUMO

The possibility of using differential pre-heating prior to supramolecular gelation to control the balance between hydrogen-bonding and aromatic stacking interactions in supramolecular gels and obtain consequent systematic regulation of structure and properties is demonstrated. Using a model aromatic peptide amphiphile, Fmoc-tyrosyl-leucine (Fmoc-YL) and a combination of fluorescence, infrared, circular dichroism and NMR spectroscopy, it is shown that the balance of these interactions can be adjusted by temporary exposure to elevated temperatures in the range 313-365 K, followed by supramolecular locking in the gel state by cooling to room temperature. Distinct regimes can be identified regarding the balance between H-bonding and aromatic stacking interactions, with a transition point at 333 K. Consequently, gels can be obtained with customizable properties, including supramolecular chirality and gel stiffness. The differential supramolecular structures also result in changes in proteolytic stability, highlighting the possibility of obtaining a range of supramolecular architectures from a single molecular structure by simply controlling the pre-assembly temperature.

8.
J Nat Prod ; 82(2): 211-220, 2019 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-30735391

RESUMO

In order to accelerate the isolation and characterization of structurally new or novel secondary metabolites, it is crucial to develop efficient strategies that prioritize samples with greatest promise early in the workflow so that resources can be utilized in a more efficient and cost-effective manner. We have developed a metrics-based prioritization approach using exact LC-HRMS, which uses data for 24 618 marine natural products held in the PharmaSea database. Each sample was evaluated and allocated a metric score by a software algorithm based on the ratio of new masses over the total (sample novelty), ratio of known masses over the total (chemical novelty), number of peaks above a defined peak area threshold (sample complexity), and peak area (sample diversity). Samples were then ranked and prioritized based on these metric scores. To validate the approach, eight marine sponges and six tunicate samples collected from the Fiji Islands were analyzed, metric scores calculated, and samples targeted for isolation and characterization of new compounds. Structures of new compounds were elucidated by spectroscopic techniques, including 1D and 2D NMR, MS, and MS/MS. Structures were confirmed by computer-assisted structure elucidation methods (CASE) using the ACD/Structure Elucidator Suite.


Assuntos
Produtos Biológicos/isolamento & purificação , Cromatografia Líquida/métodos , Descoberta de Drogas/métodos , Espectrometria de Massas/métodos , Poríferos/química , Urocordados/química , Animais , Bases de Dados Factuais , Espectroscopia de Ressonância Magnética
9.
J Biol Chem ; 292(33): 13843-13852, 2017 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-28663371

RESUMO

Phototropins (phots) are plasma membrane-associated serine/threonine kinases that coordinate a range of processes linked to optimizing photosynthetic efficiency in plants. These photoreceptors contain two light-, oxygen-, or voltage-sensing (LOV) domains within their N terminus, with each binding one molecule of flavin mononucleotide as a UV/blue light-absorbing chromophore. Although phots contain two LOV domains, light-induced activation of the C-terminal kinase domain and subsequent receptor autophosphorylation is controlled primarily by the A'α-LOV2-Jα photosensory module. Mutations that disrupt interactions between the LOV2 core and its flanking helical segments can uncouple this mode of light regulation. However, the impact of these mutations on phot function in Arabidopsis has not been explored. Here we report that histidine substitution of Arg-472 located within the A'α-helix of Arabidopsis phot1 constitutively activates phot1 kinase activity in vitro without affecting LOV2 photochemistry. Expression analysis of phot1 R472H in the phot-deficient mutant confirmed that it is autophosphorylated in darkness in vivo but unable to initiate phot1 signaling in the absence of light. Instead, we found that phot1 R472H is poorly functional under low-light conditions but can restore phototropism, chloroplast accumulation, stomatal opening, and leaf positioning and expansion at higher light intensities. Our findings suggest that Arabidopsis can adapt to the elevated phosphorylation status of the phot1 R472H mutant in part by reducing its stability, whereas the activity of the mutant under high-light conditions can be attributed to additional increases in LOV2-mediated photoreceptor autophosphorylation.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Proteínas de Ligação a DNA/metabolismo , Fosfoproteínas/metabolismo , Plantas Geneticamente Modificadas/enzimologia , Processamento de Proteína Pós-Traducional , Substituição de Aminoácidos , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/efeitos da radiação , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Dicroísmo Circular , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Ativação Enzimática/efeitos da radiação , Estabilidade Enzimática/efeitos da radiação , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Isoenzimas/genética , Isoenzimas/metabolismo , Luz , Fosfoproteínas/química , Fosfoproteínas/genética , Fosforilação/efeitos da radiação , Processos Fotoquímicos , Fototropismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Plantas Geneticamente Modificadas/efeitos da radiação , Mutação Puntual , Conformação Proteica em alfa-Hélice , Domínios e Motivos de Interação entre Proteínas , Processamento de Proteína Pós-Traducional/efeitos da radiação , Proteínas Serina-Treonina Quinases , Estabilidade Proteica/efeitos da radiação , Proteínas Recombinantes de Fusão/metabolismo
10.
Photosynth Res ; 135(1-3): 9-21, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28567613

RESUMO

Rhodopseudomonas palustris is a species of purple photosynthetic bacteria that has a multigene family of puc genes that encode the alpha and beta apoproteins, which form the LH2 complexes. A genetic dissection strategy has been adopted in order to try and understand which spectroscopic form of LH2 these different genes produce. This paper presents a characterisation of one of the deletion mutants generated in this program, the pucBAd only mutant. This mutant produces an unusual spectroscopic form of LH2 that only has a single large NIR absorption band at 800 nm. Spectroscopic and pigment analyses on this complex suggest that it has basically a similar overall structure as that of the wild-type HL LH2 complex. The mutant has the unique phenotype where the mutant LH2 complex is only produced when cells are grown at LL. At HL the mutant only produces the LH1-RC core complex.


Assuntos
Deleção de Genes , Genes Bacterianos , Complexos de Proteínas Captadores de Luz/genética , Rodopseudomonas/genética , Bacterioclorofilas/metabolismo , Carotenoides/metabolismo , Fracionamento Químico , Dicroísmo Circular , Cristalização , Modelos Moleculares , Peptídeos/metabolismo , Rodopseudomonas/crescimento & desenvolvimento , Rodopseudomonas/ultraestrutura
11.
Int Rev Psychiatry ; 30(5): 117-135, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30522370

RESUMO

Pharmacotherapy for opioid addiction with methadone, buprenorphine, and naltrexone has proven efficacy in reducing illicit opioid use. These treatments are under-utilized among opioid-addicted individuals on parole, probation, or in drug courts. This paper examines the peer-reviewed literature on the effectiveness of pharmacotherapy for opioid addiction of adults under community-based criminal justice supervision in the US. Compared to general populations, there are relatively few papers addressing the separate impact of pharmacotherapy on individuals under community supervision. Tentative conclusions can be drawn from the extant literature. Reasonable evidence exists that illicit opioid use and self-reported criminal behaviour decline after treatment entry, and that these outcomes are as favourable among individuals under criminal justice supervision as the general treatment population. Surprisingly, there is no conclusive evidence regarding the extent to which pharmacotherapy impacts the likelihood of arrest and incarceration among individuals under supervision. However, given the proven efficacy of these three medications in reducing illicit opioid use and the evidence that, in the general population, methadone and buprenorphine treatment are associated with reduction in overdose mortality, the use of all three pharmacotherapies among patients under criminal justice supervision should be expanded while more data are collected on their impact on arrest and incarceration.


Assuntos
Buprenorfina/administração & dosagem , Direito Penal , Metadona/administração & dosagem , Naltrexona/administração & dosagem , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Prisões , Humanos , Tratamento de Substituição de Opiáceos
12.
PLoS Pathog ; 11(2): e1004673, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25658827

RESUMO

Adenoviruses are common pathogens, mostly targeting ocular, gastrointestinal and respiratory cells, but in some cases infection disseminates, presenting in severe clinical outcomes. Upon dissemination and contact with blood, coagulation factor X (FX) interacts directly with the adenovirus type 5 (Ad5) hexon. FX can act as a bridge to bind heparan sulphate proteoglycans, leading to substantial Ad5 hepatocyte uptake. FX "coating" also protects the virus from host IgM and complement-mediated neutralisation. However, the contribution of FX in determining Ad liver transduction whilst simultaneously shielding the virus from immune attack remains unclear. In this study, we demonstrate that the FX protection mechanism is not conserved amongst Ad types, and identify the hexon hypervariable regions (HVR) of Ad5 as the capsid proteins targeted by this host defense pathway. Using genetic and pharmacological approaches, we manipulate Ad5 HVR interactions to interrogate the interplay between viral cell transduction and immune neutralisation. We show that FX and inhibitory serum components can co-compete and virus neutralisation is influenced by both the location and extent of modifications to the Ad5 HVRs. We engineered Ad5-derived HVRs into the rare, native non FX-binding Ad26 to create Ad26.HVR5C. This enabled the virus to interact with FX at high affinity, as quantified by surface plasmon resonance, FX-mediated cell binding and transduction assays. Concomitantly, Ad26.HVR5C was also sensitised to immune attack in the absence of FX, a direct consequence of the engineered HVRs from Ad5. In both immune competent and deficient animals, Ad26.HVR5C hepatic gene transfer was mediated by FX following intravenous delivery. This study gives mechanistic insight into the pivotal role of the Ad5 HVRs in conferring sensitivity to virus neutralisation by IgM and classical complement-mediated attack. Furthermore, through this gain-of-function approach we demonstrate the dual functionality of FX in protecting Ad26.HVR5C against innate immune factors whilst determining liver targeting.


Assuntos
Adenovírus Humanos/imunologia , Anticorpos Antivirais/imunologia , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/imunologia , Fator X/imunologia , Infecções por Adenovirus Humanos/imunologia , Infecções por Adenovirus Humanos/prevenção & controle , Adenovírus Humanos/genética , Animais , Anticorpos Neutralizantes/imunologia , Antígenos Virais/genética , Antígenos Virais/imunologia , Linhagem Celular Tumoral , Variação Genética/genética , Vetores Genéticos/genética , Células HEK293 , Células HeLa , Humanos , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Ressonância de Plasmônio de Superfície , Transdução Genética , Ligação Viral
13.
Curr Psychiatry Rep ; 19(6): 35, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28526967

RESUMO

PURPOSE OF REVIEW: The recent heroin and prescription opioid misuse epidemic has led to a sharp increase in the number of opioid overdose deaths in the USA. Notwithstanding the availability of three FDA-approved medications (methadone, buprenorphine, and naltrexone) to treat opioid use disorder, these medications are underutilized. This paper provides an update from the recent peer-reviewed literature on barriers to the use of these medications. FINDINGS: These barriers are interrelated and can be categorized as financial, regulatory, geographic, attitudinal, and logistic. While financial barriers are common to all three medications, other barriers are medication-specific. The adverse impact of the current opioid epidemic on public health can be reduced by increasing access to effective pharmacotherapy for opioid use disorder.


Assuntos
Analgésicos Opioides/uso terapêutico , Acessibilidade aos Serviços de Saúde , Antagonistas de Entorpecentes/uso terapêutico , Tratamento de Substituição de Opiáceos/métodos , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Buprenorfina/uso terapêutico , Humanos , Metadona/uso terapêutico , Naltrexona/uso terapêutico , Estados Unidos
14.
Subst Abus ; 38(4): 382-388, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28686545

RESUMO

BACKGROUND: The Problem Oriented Screening Instrument for Teenagers (POSIT) substance use/abuse subscale has been validated with high school students, adolescents with criminal justice involvement, and adolescent substance use treatment samples using the Diagnostic and Statistical Manual of Mental Disorders (DSM)-III-R and DSM-IV. This study examines the concurrent validity of the POSIT's standard 17-item substance use/abuse subscale and a revised, shorter 11-item version using DSM-5 substance use disorder diagnoses. METHODS: Adolescents (N = 525; 93% African American, 55% female) 12-17 years of age awaiting primary care appointments at a Federally Qualified Health Center in Baltimore, Maryland completed the 17-item POSIT substance use/abuse subscale and items from a modified World Mental Health Composite International Diagnostic Interview corresponding to DSM-5 alcohol use disorder (AUD) and cannabis use disorder (CUD). Receiver operating characteristic curves, sensitivities, and specificities were examined with DSM-5 AUD, CUD, and a diagnosis of either or both disorders for the standard and revised subscales using risk cutoffs of either 1 or 2 POSIT "yes" responses. RESULTS: For the 17-item subscale, sensitivities were generally high using either cutoff (range: 0.79-1.00), although a cutoff of 1 was superior (sensitivities were 1.00 for AUD, CUD, and for either disorder). Specificities were also high using either cutoff (range: 0.81-0.95) but were higher using a cutoff of 2. For the 11-item subscale, a cutoff of 1 yielded higher sensitivities than a cutoff of 2 (ranges for 1 and 2: 0.96-1.00 and 0.79-0.86, respectively). Specificities for this subscale were higher using a cutoff of 2 (ranges for 1 and 2: 0.82-0.89 and 0.89-0.96, respectively). CONCLUSIONS: Findings suggest that the POSIT's substance use/abuse subscale is a potentially useful tool for screening adolescents in primary care for AUD or CUD using a cutoff of 1 or 2. The briefer, revised subscale may be preferable to the standard subscale in busy pediatric practices.


Assuntos
Comportamento do Adolescente/psicologia , Técnicas e Procedimentos Diagnósticos/normas , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adolescente , Criança , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Atenção Primária à Saúde , Psicometria , Reprodutibilidade dos Testes , Transtornos Relacionados ao Uso de Substâncias/psicologia , População Urbana/estatística & dados numéricos
15.
Angew Chem Int Ed Engl ; 56(4): 1141-1145, 2017 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-27900812

RESUMO

Herein, we report a hybrid polyoxometalate organic-inorganic compound, Na2 [(HGMP)2 Mo5 O15 ]⋅7 H2 O (1; where GMP=guanosine monophosphate), which spontaneously assembles into a structure with dimensions that are strikingly similar to those of the naturally occurring left-handed Z-form of DNA. The helical parameters in the crystal structure of the new compound, such as rise per turn and helical twist per dimer, are nearly identical to this DNA conformation, allowing a close comparison of the two structures. Solution circular dichroism studies show that compound 1 also forms extended secondary structures in solution. Gel electrophoresis studies demonstrate the formation of non-covalent adducts with natural plasmids. Thus we show a route by which simple hybrid inorganic-organic monomers, such as compound 1, can spontaneously assemble into a double helix without the need for a covalently connected linear sequence of nucleic acid base pairs.


Assuntos
DNA Forma Z/química , Compostos Organometálicos/síntese química , Modelos Moleculares , Molibdênio/química , Conformação de Ácido Nucleico , Compostos Organometálicos/química , Oxigênio/química , Sódio/química , Compostos de Tungstênio/química
16.
PLoS Pathog ; 10(2): e1003898, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24516380

RESUMO

Lectin-like bacteriocins consist of tandem monocot mannose-binding domains and display a genus-specific killing activity. Here we show that pyocin L1, a novel member of this family from Pseudomonas aeruginosa, targets susceptible strains of this species through recognition of the common polysaccharide antigen (CPA) of P. aeruginosa lipopolysaccharide that is predominantly a homopolymer of D-rhamnose. Structural and biophysical analyses show that recognition of CPA occurs through the C-terminal carbohydrate-binding domain of pyocin L1 and that this interaction is a prerequisite for bactericidal activity. Further to this, we show that the previously described lectin-like bacteriocin putidacin L1 shows a similar carbohydrate-binding specificity, indicating that oligosaccharides containing D-rhamnose and not D-mannose, as was previously thought, are the physiologically relevant ligands for this group of bacteriocins. The widespread inclusion of d-rhamnose in the lipopolysaccharide of members of the genus Pseudomonas explains the unusual genus-specific activity of the lectin-like bacteriocins.


Assuntos
Bacteriocinas/metabolismo , Lipopolissacarídeos/metabolismo , Pseudomonas aeruginosa/metabolismo , Ramnose/metabolismo , Sequência de Aminoácidos , Bacteriocinas/química , Immunoblotting , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Reação em Cadeia da Polimerase , Estrutura Quaternária de Proteína , Pseudomonas aeruginosa/química , Ramnose/química
17.
Chemistry ; 22(26): 8943-54, 2016 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-27219069

RESUMO

This study reports a detailed biophysical analysis of the DNA binding and cytotoxicity of six platinum complexes (PCs). They are of the type [Pt(PL )(SS-dach)]Cl2 , where PL is a polyaromatic ligand and SS-dach is 1S,2S-diaminocyclohexane. The DNA binding of these complexes was investigated using six techniques including ultraviolet and fluorescence spectroscopy, linear dichroism, synchrotron radiation circular dichroism, isothermal titration calorimetry and mass spectrometry. This portfolio of techniques has not been extensively used to study the interactions of such complexes previously; each assay provided unique insight. The in vitro cytotoxicity of these compounds was studied in ten cell lines and compared to the effects of their R,R enantiomers; activity was very high in Du145 and SJ-G2 cells, with some submicromolar IC50 values. In terms of both DNA affinity and cytotoxicity, complexes of 5,6-dimethyl-1,10-phenanthroline and 2,2'-bipyridine exhibited the greatest and least activity, respectively, suggesting that there is some correlation between DNA binding and cytotoxicity.


Assuntos
Antineoplásicos/química , Complexos de Coordenação/química , DNA/química , 2,2'-Dipiridil/química , Antineoplásicos/síntese química , Antineoplásicos/toxicidade , Calorimetria , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Complexos de Coordenação/síntese química , Complexos de Coordenação/toxicidade , DNA/metabolismo , Humanos , Substâncias Intercalantes/química , Espectrometria de Massas , Fenantrolinas/química , Platina/química , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta
19.
J Nurs Adm ; 46(11): 605-612, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27755212

RESUMO

OBJECTIVE: The objectives of this study were to examine differences in nurse engagement in shared governance across hospitals and to determine the relationship between nurse engagement and patient and nurse outcomes. BACKGROUND: There is little empirical evidence examining the relationship between shared governance and patient outcomes. METHODS: A secondary analysis of linked cross-sectional data was conducted using nurse, hospital, and Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey data. RESULTS: Engagement varied widely across hospitals. In hospitals with greater levels of engagement, nurses were significantly less likely to report unfavorable job outcomes and poor ratings of quality and safety. Higher levels of nurse engagement were associated with higher HCAHPS scores. CONCLUSIONS: A professional practice environment that incorporates shared governance may serve as a valuable intervention for organizations to promote optimal patient and nurse outcomes.


Assuntos
Comportamento Cooperativo , Relações Interprofissionais , Recursos Humanos de Enfermagem Hospitalar/psicologia , Equipe de Enfermagem/organização & administração , Satisfação do Paciente , Esgotamento Profissional/prevenção & controle , Feminino , Humanos , Masculino , Pacientes/estatística & dados numéricos , Inquéritos e Questionários , Estados Unidos
20.
Biochim Biophys Acta ; 1837(11): 1849-1860, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25111749

RESUMO

This study systematically investigated the different types of LH2 produced by Allochromatium (Alc.) vinosum, a photosynthetic purple sulphur bacterium, in response to variations in growth conditions. Three different spectral forms of LH2 were isolated and purified, the B800-820, B800-840 and B800-850 LH2 types, all of which exhibit an unusual split 800 peak in their low temperature absorption spectra. However, it is likely that more forms are also present. Relatively more B800-820 and B800-840 are produced under low light conditions, while relatively more B800-850 is produced under high light conditions. Polypeptide compositions of the three different LH2 types were determined by a combination of HPLC and TOF/MS. The B800-820, B800-840 and B800-850 LH2 types all have a heterogeneous polypeptide composition, containing multiple types of both α and ß polypeptides, and differ in their precise polypeptide composition. They all have a mixed carotenoid composition, containing carotenoids of the spirilloxanthin series. In all cases the most abundant carotenoid is rhodopin; however, there is a shift towards carotenoids with a higher conjugation number in LH2 complexes produced under low light conditions. CD spectroscopy, together with the polypeptide analysis, demonstrates that these Alc. vinosum LH2 complexes are more closely related to the LH2 complex from Phs. molischianum than they are to the LH2 complexes from Rps. acidophila.

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