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1.
Cell ; 185(11): 1860-1874.e12, 2022 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-35568033

RESUMO

Two mycobacteriophages were administered intravenously to a male with treatment-refractory Mycobacterium abscessus pulmonary infection and severe cystic fibrosis lung disease. The phages were engineered to enhance their capacity to lyse M. abscessus and were selected specifically as the most effective against the subject's bacterial isolate. In the setting of compassionate use, the evidence of phage-induced lysis was observed using molecular and metabolic assays combined with clinical assessments. M. abscessus isolates pre and post-phage treatment demonstrated genetic stability, with a general decline in diversity and no increased resistance to phage or antibiotics. The anti-phage neutralizing antibody titers to one phage increased with time but did not prevent clinical improvement throughout the course of treatment. The subject received lung transplantation on day 379, and systematic culturing of the explanted lung did not detect M. abscessus. This study describes the course and associated markers of a successful phage treatment of M. abscessus in advanced lung disease.


Assuntos
Bacteriófagos , Fibrose Cística , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriófagos/genética , Fibrose Cística/tratamento farmacológico , Humanos , Pulmão , Masculino , Infecções por Mycobacterium não Tuberculosas/terapia , Mycobacterium abscessus/fisiologia
2.
Nature ; 631(8022): 884-890, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39020178

RESUMO

Plastic production reached 400 million tons in 2022 (ref. 1), with packaging and single-use plastics accounting for a substantial amount of this2. The resulting waste ends up in landfills, incineration or the environment, contributing to environmental pollution3. Shifting to biodegradable and compostable plastics is increasingly being considered as an efficient waste-management alternative4. Although polylactide (PLA) is the most widely used biosourced polymer5, its biodegradation rate under home-compost and soil conditions remains low6-8. Here we present a PLA-based plastic in which an optimized enzyme is embedded to ensure rapid biodegradation and compostability at room temperature, using a scalable industrial process. First, an 80-fold activity enhancement was achieved through structure-based rational engineering of a new hyperthermostable PLA hydrolase. Second, the enzyme was uniformly dispersed within the PLA matrix by means of a masterbatch-based melt extrusion process. The liquid enzyme formulation was incorporated in polycaprolactone, a low-melting-temperature polymer, through melt extrusion at 70 °C, forming an 'enzymated' polycaprolactone masterbatch. Masterbatch pellets were integrated into PLA by melt extrusion at 160 °C, producing an enzymated PLA film (0.02% w/w enzyme) that fully disintegrated under home-compost conditions within 20-24 weeks, meeting home-composting standards. The mechanical and degradation properties of the enzymated film were compatible with industrial packaging applications, and they remained intact during long-term storage. This innovative material not only opens new avenues for composters and biomethane production but also provides a feasible industrial solution for PLA degradation.


Assuntos
Plásticos Biodegradáveis , Biodegradação Ambiental , Enzimas Imobilizadas , Hidrolases , Poliésteres , Engenharia de Proteínas , Plásticos Biodegradáveis/química , Plásticos Biodegradáveis/metabolismo , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Hidrolases/metabolismo , Hidrolases/química , Poliésteres/química , Poliésteres/metabolismo , Solo/química , Temperatura , Estabilidade Enzimática , Compostagem
3.
J Psychosoc Oncol ; 42(1): 148-158, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37114974

RESUMO

This study examines feedback from two interventions, hypnosis and progressive muscle relaxation (PMR), to improve body image in a randomized phase II trial. Eighty-seven women were randomized either to hypnosis or PMR. Sixty-three women (72%) were motivated to write comments about their study experience. These comments were explored in an unplanned qualitative analysis. Thematic analysis generated five themes, suggesting both hypnosis and PMR may improve body image through the ability to relax and manage stress, sleep better, improve mood and create a mind-body connection. Sexual health emerged as a theme for participants in only the hypnosis group which suggests hypnotic suggestions for body image may improve overall sexual health. Additional research is needed to assess this further.


Assuntos
Treinamento Autógeno , Hipnose , Feminino , Humanos , Imagem Corporal , Hipnose/métodos
4.
Am J Physiol Endocrinol Metab ; 322(4): E366-E381, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35224983

RESUMO

This review aims to describe and compare porcine models of metabolic syndrome. This syndrome and its associated secondary comorbidities are set to become the greatest challenge to healthcare providers and policy makers in the coming century. However, an incomplete understanding of the pathogenesis has left significant knowledge gaps in terms of efficacious therapeutics. To further our comprehension and, in turn, management of metabolic syndrome, appropriate high-fidelity models of the disease complex are of great importance. In this context, our review aims to assess the most promising porcine models of metabolic syndrome currently available for their similarity to the human phenotype. In addition, we aim to highlight the strengths and shortcomings of each model in an attempt to identify the most appropriate application of each. Although no porcine model perfectly recapitulates the human metabolic syndrome, several pose satisfactory approximations. The Ossabaw miniature swine in particular represents a highly translatable model that develops each of the core parameters of the syndrome with many of the associated secondary comorbidities. Future high-fidelity porcine models of metabolic syndrome need to focus on secondary sequelae replication, which may require extended induction period to reveal.


Assuntos
Síndrome Metabólica , Animais , Modelos Animais de Doenças , Progressão da Doença , Síndrome Metabólica/etiologia , Suínos , Porco Miniatura
5.
Plant Cell Environ ; 45(10): 2898-2905, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35854434

RESUMO

The phloem is a key player in whole plant functioning-transporting carbon from sites of production to sites of demand-and is likely influenced by drought due to its dependence on water for generating pressure-driven bulk flow transport. Yet, phloem functioning during drought remains largely unknown due to a lack of experimental studies. Here, we use a phloem-bleeding species, Ricinus communis, to investigate phloem loss-of-function in the context of leaf physiological processes, the mechanisms of phloem turgor maintenance during drought, and the role of turgor in phloem loss-of-function. We found that the solute concentration in the phloem sap doubled over the drought, which allowed phloem turgor to be maintained past the point at which leaves have reached permanent stomatal closure. We also found that phloem turgor did not decline before bleeding ceased, which suggests that phloem bleeding ceassation (interpreted as the cessation of transport) occurred when the phloem still had turgor. In sum, our findings highlight the robustness of phloem functioning, with important implications for forecasting whole-plant carbon dynamics and drought-induced tree mortality.


Assuntos
Secas , Floema , Carbono , Floema/fisiologia , Folhas de Planta/fisiologia , Ricinus/fisiologia , Árvores , Água
6.
Prev Med ; 163: 107192, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35963310

RESUMO

Precision health seeks to optimise behavioural interventions by delivering personalised support to those in need, when and where they need it. Conceptualised a decade ago, progress toward this vision of personally relevant and effective population-wide interventions continues to evolve. This scoping review aimed to map the state of precision health behaviour change intervention research. This review included studies from a broader precision health review. Six databases were searched for studies published between January 2010 and June 2020, using the terms 'precision health' or its synonyms, and including an intervention targeting modifiable health behaviour(s) that was evaluated experimentally. Thirty-one studies were included, 12 being RCTs (39%), and 17 with weak study design (55%). Most interventions targeted physical activity (27/31, 87%) and/or diet (24/31, 77%), with 74% (23/31) targeting two to four health behaviours. Interventions were personalised via human interaction in 55% (17/31) and digitally in 35% (11/31). Data used for personalising interventions was largely self-reported, by survey or diary (14/31, 45%), or digitally (14/31, 45%). Data was mostly behavioural or lifestyle (20/31, 65%), and physiologic, biochemical or clinical (15/31, 48%), with no studies utilising genetic/genomic data. This review demonstrated that precision health behaviour change interventions remain dependent on human-led, low-tech personalisation, and have not fully considered the interaction between behaviour and the social and environmental contexts of individuals. Further research is needed to understand the relationship between personalisation and intervention effectiveness, working toward the development of sophisticated and scalable behaviour change interventions that have tangible public health impact.


Assuntos
Exercício Físico , Comportamentos Relacionados com a Saúde , Terapia Comportamental , Dieta , Humanos , Estilo de Vida
7.
Bioethics ; 36(1): 25-41, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34674395

RESUMO

The increasing dementia prevalence worldwide is driving the testing of novel therapeutic approaches, such as invasive brain technologies, despite limited clinical evidence and the risk of accelerating cognitive decline. Our manuscript (a) reviews the NIH Clinicaltrials.gov database for deep brain stimulation, stem cell implantation, and gene therapy trials on people with dementia; (b) discusses issues on beneficence, nonmaleficence, and autonomy associated with these trials; and (c) proposes nine recommendations that build on elements from the Declaration of Helsinki. We found 49 preregistered high-risk trials from nine countries planning to or involving 11,801 people with Alzheimer's or Lewy body dementia or dementia secondary to Parkinson's or Huntington's disease. Most of the people with Alzheimer's who are in these trials are from North America and East Asia. There is substantial heterogeneity in the enrolment criteria, even for trials recruiting only those with Alzheimer's disease. Although most trials enrol people in mild to moderate stages of Alzheimer's disease, trials in China enrol people who have severe Alzheimer's. Our findings highlight a pressing need to review and refine the enrolment criteria for invasive neural trials in people with dementia, considering risks, potential benefits, and capacity for informed consent. As a multidisciplinary team from Australia, the USA, Canada, and Germany with expertise in neurology, neuroscience, and ethics, we examine how it is essential to balance the risks of invasive neural research in a vulnerable population with limited capacity to provide informed consent to help advance the body of knowledge regarding a disease with limited therapeutic options.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/terapia , Austrália , Encéfalo , Canadá , Humanos
8.
Vet Surg ; 51(7): 1096-1105, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35866930

RESUMO

OBJECTIVE: To report the outcomes of dogs that underwent primary repair of gastroduodenal perforations associated with the administration of nonsteroidal anti-inflammatory drugs (NSAID). A secondary objective was to identify clinicopathological findings that predisposed dogs to postoperative death. STUDY DESIGN: Retrospective study. ANIMALS: Eleven dogs with complete gastric or duodenal perforation related to administration of an NSAID that underwent primary surgical repair. METHODS: Medical records were reviewed for dogs that presented with peritonitis due to a complete gastroduodenal perforation while receiving NSAIDs between November, 2011 and January, 2021. Data collected included patient characteristics, clinical signs, clinicopathological results, surgical details, and postoperative management and outcome. RESULTS: All dogs were large breeds (mean weight 42 kg; range 22-75 kg), with a mean age of 7.35 years. Nine dogs from a total of 11 (82 %) received a concurrent corticosteroid and NSAID, or a higher dose/frequency/length of NSAID administration than recommended by the manufacturer. All gastroduodenal perforations were found in the upper gastrointestinal tract. Eight of 11 (73%) dogs survived to discharge. The median postoperative duration of follow up was 444 days (range 2-1460 days). No association was detected between ulcer size or location and mortality. CONCLUSION: Most dogs who underwent primary repair of complete gastroduodenal ulcers survived. Gastroduodenal perforations were generally due to the administration of higher or longer doses of NSAIDs, or concurrent administration of another NSAID or corticosteroid. CLINICAL SIGNIFICANCE: Primary closure may be associated with a high success rate in dogs with full thickness gastroduodenal ulcers.


Assuntos
Fármacos Antiobesidade , Doenças do Cão , Gastroenteropatias , Úlcera Péptica , Úlcera Gástrica , Corticosteroides , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Doenças do Cão/tratamento farmacológico , Doenças do Cão/cirurgia , Cães , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/cirurgia , Gastroenteropatias/veterinária , Úlcera Péptica/tratamento farmacológico , Úlcera Péptica/cirurgia , Úlcera Péptica/veterinária , Estudos Retrospectivos , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/cirurgia , Úlcera Gástrica/veterinária , Úlcera/veterinária
9.
Support Care Cancer ; 29(6): 3103-3112, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33057818

RESUMO

OBJECTIVES: The objectives were to compare patients with and without cancer who sought an integrative health (IH) consult and reasons for seeking a consult. DESIGN: Descriptive cross-sectional study that employed a secondary analysis of an integrative health database supplemented by a retrospective medical record review. SETTING/LOCATION: Integrative Medicine and Health program in a Southwestern United States academic medical center. SUBJECTS: Eight hundred thirty-nine adults over the age of 18 seeking IH consultation. RESULTS: The number of complementary therapies reported prior to consult were not significantly different between groups. The most reported complementary therapies used by cancer survivors were multivitamins, exercise, and turmeric. Patients without cancer reported significantly higher pain levels than cancer survivors. Cancer survivors reported significantly higher energy, sleep levels, overall health, spiritual wellbeing, and significantly better relationships compared to patients without cancer. Cancer survivors reported fatigue and cancer as the top reasons for IH consult. CONCLUSION: Participants without cancer reported higher levels of pain and lower levels of energy, sleep, overall health, spiritual wellbeing, and relationships compared to cancer survivors. However, cancer survivors still reported levels of unmanaged symptoms. Complementary therapy use prior to IMH consult was similar between groups; however, IMH providers recommended more treatments for patients without cancer. Our results highlight that more evidence is needed to guide IMH recommendations, especially for cancer survivors who may still be in treatment. Additionally, our results support evidence-based recommendations that all cancer survivors should be assessed for complementary therapy use and provided counseling by qualified providers on their advantages and limitations.


Assuntos
Sobreviventes de Câncer/psicologia , Medicina Integrativa/tendências , Encaminhamento e Consulta/tendências , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inquéritos e Questionários
10.
Career Dev Q ; 69(4): 313-325, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35463739

RESUMO

This article discusses the impact of the COVID-19 pandemic on workers with disabilities. Given that most employment-related literature about COVID-19 does not include people with disabilities, an in-depth exploration of the impact of COVID-19 on this population is warranted. Additionally, this article discusses the unique issues this population is facing during the pandemic, including the intersectionality of disability, race, and economic disadvantage. Suggestions for supporting people with disabilities in counseling and career-related activities, both during the COVID-19 pandemic and postpandemic, are provided.

11.
Am J Physiol Heart Circ Physiol ; 318(3): H590-H603, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32031871

RESUMO

Metabolic syndrome (MetS) is a composite of cardiometabolic risk factors, including obesity, dyslipidemia, hypertension, and insulin resistance, with a range of secondary sequelae such as nonalcoholic fatty liver disease and diastolic heart failure. This syndrome has been identified as one of the greatest global health challenges of the 21st century. Herein, we examine whether a porcine model of diet- and mineralocorticoid-induced MetS closely mimics the cardiovascular, metabolic, gut microbiota, and functional metataxonomic phenotype observed in human studies. Landrace pigs with deoxycorticosterone acetate-induced hypertension fed a diet high in fat, salt, and sugar over 12 wk were assessed for hyperlipidemia, hyperinsulinemia, and immunohistologic, echocardiographic, and hemodynamic parameters, as well as assessed for microbiome phenotype and function through 16S rRNA metataxonomic and metabolomic analysis, respectively. All MetS animals developed obesity, hyperlipidemia, insulin resistance, hypertension, fatty liver, structural cardiovascular changes including left ventricular hypertrophy and left atrial enlargement, and increased circulating saturated fatty acid levels, all in keeping with the human phenotype. A reduction in α-diversity and specific microbiota changes at phylum, family, and genus levels were also observed in this model. Specifically, this porcine model of MetS displayed increased abundances of proinflammatory bacteria coupled with increased circulating tumor necrosis factor-α and increased secondary bile acid-producing bacteria, which substantially impacted fibroblast growth factor-19 expression. Finally, a significant decrease in enteroprotective bacteria and a reduction in short-chain fatty acid-producing bacteria were also noted. Together, these data suggest that diet and mineralocorticoid-mediated development of biochemical and cardiovascular stigmata of metabolic syndrome in pigs leads to temporal gut microbiome changes that mimic key gut microbial population signatures in human cardiometabolic disease.NEW & NOTEWORTHY This study extends a prior porcine model of cardiometabolic syndrome to include systemic inflammation, fatty liver, and insulin sensitivity. Gut microbiome changes during evolution of porcine cardiometabolic disease recapitulate those in human subjects with alterations in gut taxa associated with proinflammatory bacteria, bile acid, and fatty acid pathways. This clinical scale model may facilitate design of future interventional trials to test causal relationships between gut dysbiosis and cardiometabolic syndrome at a systemic and organ level.


Assuntos
Microbioma Gastrointestinal/fisiologia , Hipertensão/microbiologia , Resistência à Insulina/fisiologia , Síndrome Metabólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/microbiologia , Animais , Glicemia/metabolismo , Colesterol/sangue , Dieta Hiperlipídica , Modelos Animais de Doenças , Ecocardiografia , Feminino , Hipertensão/metabolismo , Inflamação/metabolismo , Inflamação/microbiologia , Insulina/sangue , Síndrome Metabólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Suínos , Triglicerídeos/sangue
12.
Adv Funct Mater ; 30(25)2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32982626

RESUMO

Scaffolds made from biocompatible polymers provide physical cues to direct the extension of neurites and to encourage repair of damaged nerves. The inclusion of neurotrophic payloads in these scaffolds can substantially enhance regrowth and repair processes. However, many promising neurotrophic candidates are excluded from this approach due to incompatibilities with the polymer or with the polymer processing conditions. This work provides one solution to this problem by incorporating porous silicon nanoparticles (pSiNPs) that are pre-loaded with the therapeutic into a polymer scaffold during fabrication. The nanoparticle-drug-polymer hybrids are prepared in the form of oriented poly(lactic-co-glycolic acid) nanofiber scaffolds. We test three different therapeutic payloads: bpV(HOpic), a small molecule inhibitor of phosphatase and tensin homolog (PTEN); an RNA aptamer specific to tropomyosin-related kinase receptor type B (TrkB); and the protein nerve growth factor (NGF). Each therapeutic is loaded using a loading chemistry that is optimized to slow the rate of release of these water-soluble payloads. The drug-loaded pSiNP-nanofiber hybrids release approximately half of their TrkB aptamer, bpV(HOpic), or NGF payload in 2, 10, and >40 days, respectively. The nanofiber hybrids increase neurite extension relative to drug-free control nanofibers in a dorsal root ganglion explant assay.

13.
Magn Reson Med ; 83(4): 1458-1470, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31612545

RESUMO

PURPOSE: Estimating microstructural parameters of skeletal muscle from diffusion MRI (dMRI) signal requires understanding the relative importance of both microstructural and dMRI sequence parameters on the signal. This study seeks to determine the sensitivity of dMRI signal to variations in microstructural and dMRI sequence parameters, as well as assess the effect of noise on sensitivity. METHODS: Using a cylindrical myocyte model of skeletal muscle, numerical solutions of the Bloch-Torrey equation were used to calculate global sensitivity indices of dMRI metrics (FA, RD, MD, λ1 , λ2 , λ3 ) for wide ranges of microstructural and dMRI sequence parameters. The microstructural parameters were: myocyte diameter, volume fraction, membrane permeability, intra- and extracellular diffusion coefficients, and intra- and extracellular T2 times. Two separate pulse sequences were examined, a PGSE and a generalized diffusion-weighted sequence that accommodates a larger range of diffusion times. The effect of noise and signal averaging on the sensitivity of the dMRI metrics was examined by adding synthetic noise to the simulated signal. RESULTS: Among the examined parameters, the intracellular diffusion coefficient has the strongest effect, and myocyte diameter is more influential than permeability for FA and RD. The sensitivity indices do not vary significantly between the two pulse sequences. Also, noise strongly affects the sensitivity of the dMRI signal to microstructural variations. CONCLUSIONS: With the identification of key microstructural features that affect dMRI measurements, the reported sensitivity results can help interpret dMRI measurements of skeletal muscle in terms of the underlying microstructure and further develop parsimonious dMRI models of skeletal muscle.


Assuntos
Benchmarking , Imagem de Difusão por Ressonância Magnética , Difusão , Músculo Esquelético/diagnóstico por imagem
14.
J Org Chem ; 85(12): 8013-8020, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32469215

RESUMO

We probed tandem aldol condensations of sixteen o-hydroxyacetophenones, carrying electron-withdrawing and -donating groups at positions 4 and 5, using five molar equivalents of SiCl4 in anhydrous ethanol. Substrates carrying electron-withdrawing groups (EWGs) (0 < ∑σ > 0.63) populated the equilibria with isospiropyrans (12-74% yield), while those carrying electron-donating groups (EDGs) (∑σ < -0.31) gave flavylium salts (50-80%) or thermochromic bis-spiropyrans (73%). The results are of interest for developing novel organic materials possessing switchable photochromic and thermochromic characteristics.

15.
Curr Pain Headache Rep ; 24(2): 4, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980957

RESUMO

PURPOSE OF REVIEW: Given the growing challenges in chronic pain management coupled with the ongoing consequences of the opioid epidemic, pain management practitioners are looking into more effective, innovative, and safer alternatives to treat pain. Cannabis-based medicine had been described for hundreds of years but only recently have we seen the more scientific, evidence-based approach to its use, and ongoing investigations continue to explore its potential medical benefits. While historically more attention has been paid to the psychoactive component of the cannabis plant Δ9-tetrahydrocannabinol (THC), there have been fewer scientific studies on the medical use of the cannabidiol (CBD) - a non-psychoactive component of the cannabis plant. RECENT FINDINGS: By examining recent literature, we investigated the use of CBD and its potential role in pain management. Since there are currently no approved pharmaceutical products that contain CBD alone for the management of pain, this review focused on nabiximols (which is a combined product of THC/CBD in a 1:1 ratio) as the only pharmaceutical product available that contains CBD and is being used for the management of pain. It is difficult to definitely attribute the therapeutic properties to CBD alone since it is always administered with THC. Based on the available literature, it is difficult to make a recommendation for the use of CBD in chronic pain management. It is also important to note that there are many CBD products currently available as supplements, but these products are non-pharmaceuticals and lack the appropriate clinical studies to support their efficacy claims.


Assuntos
Canabidiol/uso terapêutico , Dor Crônica/tratamento farmacológico , Medicina Baseada em Evidências/métodos , Manejo da Dor/métodos , Dor Crônica/diagnóstico , Medicina Baseada em Evidências/tendências , Humanos , Manejo da Dor/tendências
16.
Mar Drugs ; 18(12)2020 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-33419303

RESUMO

The bioactivity-guided purification of the culture broth of the shipworm endosymbiont Teredinibacter turnerae strain 991H.S.0a.06 yielded a new fatty acid, turneroic acid (1), and two previously described oxylipins (2-3). Turneroic acid (1) is an 18-carbon fatty acid decorated by a hydroxy group and an epoxide ring. Compounds 1-3 inhibited bacterial biofilm formation in Staphylococcus epidermidis, while only 3 showed antimicrobial activity against planktonic S. epidermidis. Comparison of the bioactivity of 1-3 with structurally related compounds indicated the importance of the epoxide moiety for selective and potent biofilm inhibition.


Assuntos
Biofilmes/efeitos dos fármacos , Gammaproteobacteria , Oxilipinas/farmacologia , Simbiose/efeitos dos fármacos , Animais , Biofilmes/crescimento & desenvolvimento , Bivalves , Gammaproteobacteria/química , Testes de Sensibilidade Microbiana/métodos , Oxilipinas/isolamento & purificação , Simbiose/fisiologia
17.
Proc Natl Acad Sci U S A ; 114(1): E1-E8, 2017 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-27986953

RESUMO

Antimonide compounds are fabricated in membrane form to enable materials combinations that cannot be obtained by direct growth and to support strain fields that are not possible in the bulk. InAs/(InAs,Ga)Sb type II superlattices (T2SLs) with different in-plane geometries are transferred from a GaSb substrate to a variety of hosts, including Si, polydimethylsiloxane, and metal-coated substrates. Electron microscopy shows structural integrity of transferred membranes with thickness of 100 nm to 2.5 [Formula: see text]m and lateral sizes from [Formula: see text]m2 to [Formula: see text] cm2 Electron microscopy reveals the excellent quality of the membrane interface with the new host. The crystalline structure of the T2SL is not altered by the fabrication process, and a minimal elastic relaxation occurs during the release step, as demonstrated by X-ray diffraction and mechanical modeling. A method to locally strain-engineer antimonide-based membranes is theoretically illustrated. Continuum elasticity theory shows that up to [Formula: see text]3.5% compressive strain can be induced in an InSb quantum well through external bending. Photoluminescence spectroscopy and characterization of an IR photodetector based on InAs/GaSb bonded to Si demonstrate the functionality of transferred membranes in the IR range.

18.
BMC Microbiol ; 19(1): 33, 2019 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-30736731

RESUMO

BACKGROUND: Lactobacillus mucosae DPC 6426 has previously demonstrated potentially cardio-protective properties, in the form of dyslipidaemia and hypercholesterolemia correction in an apolipoprotein-E deficient mouse model. This study aims to characterise the manner in which this microbe may modulate host bile pool composition and immune response, in the context of cardiovascular disease. Lactobacillus mucosae DPC 6426 was assessed for bile salt hydrolase activity and specificity. The microbe was compared against several other enteric strains of the same species, as well as a confirmed bile salt hydrolase-active strain, Lactobacillus reuteri APC 2587. RESULTS: Quantitative bile salt hydrolase assays revealed that enzymatic extracts from Lactobacillus reuteri APC 2587 and Lactobacillus mucosae DPC 6426 demonstrate the greatest activity in vitro. Bile acid profiling of porcine and murine bile following incubation with Lactobacillus mucosae DPC 6426 confirmed a preference for hydrolysis of glyco-conjugated bile acids. In addition, the purified exopolysaccharide and secretome of Lactobacillus mucosae DPC 6426 were investigated for immunomodulatory capabilities using RAW264.7 macrophages. Gene expression data revealed that both fractions stimulated increases in interleukin-6 and interleukin-10 gene transcription in the murine macrophages, while the entire secretome was necessary to increase CD206 transcription. Moreover, the exopolysaccharide elicited a dose-dependent increase in nitric oxide and interleukin-10 production from RAW264.7 macrophages, concurrent with increased tumour necrosis factor-α secretion at all doses. CONCLUSIONS: This study indicates that Lactobacillus mucosae DPC 6426 modulates both bile pool composition and immune system tone in a manner which may contribute significantly to the previously identified cardio-protective phenotype.


Assuntos
Amidoidrolases/biossíntese , Bile/metabolismo , Imunomodulação , Lactobacillus/enzimologia , Lactobacillus/imunologia , Macrófagos/imunologia , Animais , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/microbiologia , Glicosiltransferases/metabolismo , Hidrólise , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Limosilactobacillus reuteri/enzimologia , Lectinas Tipo C/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/microbiologia , Receptor de Manose , Lectinas de Ligação a Manose/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Polissacarídeos Bacterianos/farmacologia , Células RAW 264.7 , Receptores de Superfície Celular/metabolismo , Suínos , Fator de Necrose Tumoral alfa/metabolismo
19.
Mol Vis ; 25: 593-xxx, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31741652

RESUMO

Purpose: To quantify the partition coefficient and the diffusion coefficient of metal-carrier proteins in the human lens capsule as a function of age. Methods: Whole lenses from human donors were incubated overnight in a solution of fluorescently labeled transferrin, albumin, or ceruloplasmin. In the central plane of the capsule thickness, fluorescence recovery after photobleaching (FRAP) experiments were conducted to measure the diffusion of the protein within the lens capsule. The anterior portion of the lens was recorded before the FRAP experiments to locate the boundaries of the anterior lens capsule and to measure the partition coefficient of the labeled proteins. The partition coefficient (P), the time to half maximum recovery of the fluorescent intensity (τ1/2), and the diffusion coefficient (D) for each protein were analyzed as a function of donor age. Results: There was no statistically significant relationship between the half maximum recovery time or the diffusion coefficient and age for transferrin (molecular weight [MW]=79.5 kDa, τ1/2=17.26±4.840 s, D=0.17±0.05 µm2/s), serum albumin (MW=66.5 kDa, τ1/2=18.45±6.110 s, D=0.17±0.06 µm2/s), or ceruloplasmin (MW=120 kDa, τ1/2=36.57±5.660 s, D=0.08±0.01 µm2/s). As expected, the larger protein (ceruloplasmin) took longer to recover fluorescent intensity due to its slower movement within the lens capsule. The partition coefficient statistically significantly increased with age for each protein (Palbumin: 0.09-0.71, Pceruloplasmin: 0.42-0.95, Ptransferrin: 0.19-1.17). Conclusions: The diffusion of heavy-metal protein carriers within the anterior lens capsule is not dependent on age, but it is dependent on the size of the protein. The permeability of the lens capsule to these heavy-metal protein carriers increases with age, suggesting that there will be a higher concentration of heavy metals in the older lens. This behavior may favor the formation of cataract, because heavy metals enhance protein oxidation through the Fenton reaction.


Assuntos
Envelhecimento/fisiologia , Recuperação de Fluorescência Após Fotodegradação , Cápsula do Cristalino/diagnóstico por imagem , Adulto , Idoso , Albuminas/metabolismo , Ceruloplasmina/metabolismo , Difusão , Humanos , Cápsula do Cristalino/metabolismo , Pessoa de Meia-Idade , Transferrina/metabolismo , Adulto Jovem
20.
J Nat Prod ; 82(4): 1024-1028, 2019 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-30793902

RESUMO

Three new pyoluteorin analogues, mindapyrroles A-C (1-3), were purified from Pseudomonas aeruginosa strain 1682U.R.0a.27, a gill-associated bacterium isolated from the tissue homogenate of the giant shipworm Kuphus polythalamius. Mindapyrroles B and C inhibit the growth of multiple pathogenic bacteria, with mindapyrrole B (2) showing the most potent antimicrobial activity and widest selectivity index over mammalian cells. Preliminary structure-activity relationship analysis showed that dimerization of the pyoluteorin moiety through a C-C linkage is detrimental to the antimicrobial activity, but addition of an aerugine unit in the methylene bridge is favorable for both the antimicrobial activity and selectivity index.


Assuntos
Bivalves/química , Pseudomonas aeruginosa/química , Pirróis/isolamento & purificação , Animais , Anti-Infecciosos/farmacologia , Pirróis/química , Pirróis/farmacologia
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