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1.
Mol Cell ; 72(1): 162-177.e7, 2018 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-30244833

RESUMEN

Histone post-translational modifications (PTMs) are important genomic regulators often studied by chromatin immunoprecipitation (ChIP), whereby their locations and relative abundance are inferred by antibody capture of nucleosomes and associated DNA. However, the specificity of antibodies within these experiments has not been systematically studied. Here, we use histone peptide arrays and internally calibrated ChIP (ICeChIP) to characterize 52 commercial antibodies purported to distinguish the H3K4 methylforms (me1, me2, and me3, with each ascribed distinct biological functions). We find that many widely used antibodies poorly distinguish the methylforms and that high- and low-specificity reagents can yield dramatically different biological interpretations, resulting in substantial divergence from the literature for numerous H3K4 methylform paradigms. Using ICeChIP, we also discern quantitative relationships between enhancer H3K4 methylation and promoter transcriptional output and can measure global PTM abundance changes. Our results illustrate how poor antibody specificity contributes to the "reproducibility crisis," demonstrating the need for rigorous, platform-appropriate validation.


Asunto(s)
Anticuerpos/genética , Inmunoprecipitación de Cromatina/métodos , Heterocromatina/genética , Histonas/genética , Anticuerpos/química , Anticuerpos/inmunología , Especificidad de Anticuerpos , Heterocromatina/química , Heterocromatina/inmunología , Código de Histonas/genética , Histonas/química , Histonas/inmunología , Humanos , Metilación , Nucleosomas/genética , Regiones Promotoras Genéticas/genética , Procesamiento Proteico-Postraduccional/genética
2.
BMC Med Educ ; 24(1): 892, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39160554

RESUMEN

BACKGROUND: International Medical Graduates (IMG) are an essential part of the international physician workforce, and exploring the predictors of success and failure for IMGs could help inform international and national physician labour workforce selection and planning. The objective of this study was to explore predictors for success for selection of IMGs into high stakes postgraduate training positions and practice and not necessarily for informing IMGs. METHODS: We searched 11 databases, including Medline, Embase and LILACS, from inception to February 2022 for studies that explored the predictors of success and failure in IMGs. We reported baseline probability, effect size in relative risk (RR), odds ratio (OR) or hazard ratio (HR) and absolute probability change for success and failure across six groups of outcomes, including success in qualifying exams, or certificate exams, successful matching into residency, retention in practice, disciplinary actions, and outcomes of IMG clinical practice. RESULTS: Twenty-five studies (375,549 participants) reported the association of 93 predictors of success and failure for IMGs. Female sex, English fluency, graduation recency, higher scores in USMLE step 2 and participation in a skill assessment program were associated with success in qualifying exams. Female sex, English fluency, previous internship and results of qualifying exams were associated with success in certification exams. Retention to work in Canada was associated with several factors, including male sex, graduating within the past five years, and completing residency over fellowships. In the UK, IMGs and candidates who attempted PLAB part 1, ≥ 4 times vs. first attempters, and candidates who attempted PLAB part 2, ≥ 3 times vs. first attempters were more likely to be censured in future practice. Patients treated by IMGs had significantly lower mortalities than those treated by US graduates, and patients of IMGs had lower mortalities [OR: 0.82 (95% CI: 0.62, 0.99)] than patients of US citizens who trained abroad. CONCLUSIONS: This study informed factors associated with the success and failure of IMGs and is the first systematic review on this topic, which can inform IMG selection and future studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42021252678.


Asunto(s)
Médicos Graduados Extranjeros , Estudios Observacionales como Asunto , Médicos Graduados Extranjeros/estadística & datos numéricos , Humanos , Competencia Clínica , Educación de Postgrado en Medicina , Internado y Residencia , Femenino
3.
Brain Behav Immun ; 112: 220-234, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37315702

RESUMEN

Originally identified in fibroblasts, Protease Inhibitor (PI)16 was recently shown to be crucial for the development of neuropathic pain via effects on blood-nerve barrier permeability and leukocyte infiltration, though its impact on inflammatory pain has not been established. Using the complete Freund's Adjuvant inflammatory pain model, we show that Pi16-/- mice are protected against sustained inflammatory pain. Accordingly, intrathecal delivery of a PI16 neutralizing antibody in wild-type mice prevented sustained CFA pain. In contrast to neuropathic pain models, we did not observe any changes in blood-nerve barrier permeability due to PI16 deletion. Instead, Pi16-/- mice display reduced macrophage density in the CFA-injected hindpaw. Furthermore, there was a significant bias toward CD206hi (anti-inflammatory) macrophages in the hindpaw and associated dorsal root ganglia. Following CFA, intrathecal depletion of CD206+ macrophages using mannosylated clodronate liposomes promoted sustained pain in Pi16-/- mice. Similarly, an IL-10 neutralizing antibody also promoted sustained CFA pain in the Pi16-/ when administered intrathecally. Collectively, our results point to fibroblast-derived PI16 mediating substantial differences in macrophage phenotype in the pain neuroaxis under conditions of inflammation. The co-expression of PI16 alongside fibroblast markers in human DRG raise the likelihood that a similar mechanism operates in human inflammatory pain states. Collectively, our findings may have implications for targeting fibroblast-immune cell crosstalk for the treatment of chronic pain.


Asunto(s)
Dolor Crónico , Neuralgia , Ratones , Humanos , Animales , Inflamación , Macrófagos , Fibroblastos , Anticuerpos Neutralizantes/farmacología , Ganglios Espinales , Hiperalgesia , Proteínas Portadoras , Glicoproteínas
4.
Indian J Palliat Care ; 29(3): 292-311, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37700900

RESUMEN

Objectives: Patient Health Questionnaire-9 (PHQ-9) in Indian settings is yet not very often used in palliative care with the Hindi-speaking population. The Hindi version of PHQ-9 is available but its cultural adaptation to the Hindi-speaking population in North India receiving palliative care services is required to be tested. PHQ-9 as a depression screening questionnaire may help to identify depression symptoms among patients with cancer. This study aimed to examine the cultural equivalence of PHQ-9 Hindi for use with patients with cancer receiving palliative care services in North India. Material and Methods: Based on the standard methodology of translation and adaptation of the scale, the following process was used: (i) Two focused group discussions with 17 experts working in a cancer palliative care setting, (ii) qualitative interviewing with 11 patients, and (iii) research team review. All interviews were audio recorded, transcribed, and item-wise content analysis was conducted. Results: A few difficult phrases in the original PHQ-9 were 'dilchaspi', 'avasadgrast', 'kam urja', 'nakaam', parivar ko neecha dhikhana and 'ashthir' which were changed to Kam Mann Lagna, Mann Dukhi hona, kamjori, saksham nahi hain' 'asafal', Parivar ko nirash karna' and 'bechain,' respectively. Two items, namely no. 6 and 8 were changed to shorten the length for appropriately conveying the meaning. Conclusion: Hindi language involves various dialects which change from region to region bringing variations in understanding the meaning of the words. It is recommended that culturally equivalent scales are used in practice and research. PHQ-9 is now culturally adapted for the Hindi-speaking population in North India. PHQ-9 will help identidy depressive symptoms at an early stage. Psychometric testing of PHQ-9 is underway.

5.
Rev Cardiovasc Med ; 23(12): 411, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39076675

RESUMEN

The racial/ethnic disparities in cardiometabolic risk factors and cardiovascular diseases (CVD) are prominent in non-Hispanic Black adults and other United States (U.S.) sub-populations, with evidence of differential access and quality of health care. High blood pressure (BP) is the most potent and prevalent risk factor for adverse cardiovascular (CV) outcomes across all populations globally, but especially in the non-Hispanic Black adults in the U.S. The use of sodium-glucose cotransporter-2 inhibitors (SGLT2is) demonstrate favorable effects in patients with and without type 2 diabetes (T2DM) in CVD especially for heart failure (HF), as the contemporary clinical practice recommendations and standards of care advocate. The beneficial effects of SGLT2is have been most profoundly documented with HF, including reduced (HFrEF) or preserved ejection fraction (HFpEF), and chronic kidney disease (CKD) with T2DM. Given that hypertension (HTN), CVD, HF, and CKD are significantly greater in certain racial/ethnic populations, the potential impact of SGLT2is will be more significant on the excess cardiometabolic and renal disease, especially in the Black patients. Moreover, there is a need for increased diverse representation in clinical trials. Inclusion of larger members of various racial/ethnic populations may assure that new and emerging data accurately reflect the diversity of the U.S. population. This review highlights potential benefits of SGLT2is, as noted in the most recent literature, and their BP-lowering impact on potentially reducing CV disparities, especially in Black adults. Furthermore, this commentary emphasizes the need to increase diversity in clinical trials to reduce the disparity gaps.

6.
Ann Fam Med ; 18(2): 110-117, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32152014

RESUMEN

PURPOSE: Online programs may help to engage patients in advance care planning in outpatient settings. We sought to implement an online advance care planning program, PREPARE (Prepare for Your Care; http://www.prepareforyourcare.org), at home and evaluate the changes in advance care planning engagement among patients attending outpatient clinics. METHODS: We undertook a prospective before-and-after study in 15 primary care clinics and 2 outpatient cancer centers in Canada. Patients were aged 50 years or older (primary care) or 18 years or older (cancer care) and free of cognitive impairment. They used the PREPARE website over 6 weeks, with reminders sent at 2 or 4 weeks. We used the 55-item Advance Care Planning Engagement Survey, which measures behavior change processes (knowledge, contemplation, self-efficacy, readiness) on 5-point scales and actions relating to substitute decision makers, quality of life, flexibility for the decision maker, and asking doctors questions on an overall scale from 0 to 21; higher scores indicate greater engagement. RESULTS: In total, 315 patients were screened and 172 enrolled, of whom 75% completed the study (mean age = 65.6 years, 51% female, 35% had cancer). The mean behavior change process score was 2.9 (SD 0.8) at baseline and 3.5 (SD 0.8) at follow-up (mean change = 0.6; 95% CI, 0.49-0.73); the mean action measure score was 4.0 (SD 4.9) at baseline and 5.2 (SD 5.4) at follow-up (mean change = 1.2; 95% CI, 0.54-1.77). The effect size was moderate (0.75) for the former and small (0.23) for the latter. Findings were similar in both primary care and cancer care populations. CONCLUSIONS: Implementation of the online PREPARE program in primary care and cancer care clinics increased advance care planning engagement among patients.


Asunto(s)
Planificación Anticipada de Atención , Toma de Decisiones , Internet , Participación del Paciente/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Canadá , Estudios Controlados Antes y Después , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Atención Primaria de Salud , Estudios Prospectivos , Encuestas y Cuestionarios
7.
Org Biomol Chem ; 18(21): 4104-4113, 2020 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-32432294

RESUMEN

An expedient and efficient synthetic method was developed for the oxidative cross dehydrogenative coupling reaction between 4-hydroxydithiocoumarin and indole at the C-3 position regio-selectively using a combination of 10 mol% molecular iodine and TBHP in the presence of 10 mol% CuBr2 as an additive at room temperature. Mild reaction conditions, good yields and a broad substrate scope are some of the salient features of the present protocol. Additionally, the synthesized 3-sulfenylindoles derived from 4-hydroxydithiocoumarin were converted into biologically active sulfone derivatives. Interestingly, some of the compounds exhibit anti-cell proliferative activity on breast cancer (MCF-7) cells due to reactive oxygen species (ROS) mediated cell damage.

8.
Fam Pract ; 37(2): 219-226, 2020 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-31536615

RESUMEN

BACKGROUND: People who engage in advance care planning (ACP) are more likely to receive health care that is concordant with their goals at the end of life. Little discussion of ACP occurs in primary care. OBJECTIVE: The objective of this study was to describe primary care clinicians' perspectives on having ACP conversations with their patients. METHODS: We conducted a survey of family physicians and non-physician clinicians in primary care in 2014-2015. We compared family physicians and non-physician clinicians on willingness, confidence, participation and acceptability for other clinicians to engage in six aspects of ACP (initiating, exchanging information, decision coaching, finalizing plans, helping communicate plans with family members and other health professionals) on scales from 0 = not at all/extremely unacceptable to 6 = very/all the time/extremely acceptable. RESULTS: The response rate was 72% (n = 117) among family physicians and 69% (n = 64) among non-physician clinicians. Mean ratings (standard deviation [SD]) of willingness were high (4.5 [1.4] to 5.0 [1.2] for physicians; 3.4 [1.8] to 4.6 [1.6] non-physician clinicians). There was little participation (mean ratings 2.4 [1.7] to 2.7 [1.6] for physicians, 1.0 [1.5] to 1.4 [1.7] for non-physician clinicians). Non-physician clinicians rated confidence statistically significantly lower than physicians for all ACP aspects. Acceptability for non-physician clinician involvement was high in both groups (mean acceptability ratings greater than 4). CONCLUSION: Current engagement of primary care clinicians in ACP is low. Given the high willingness and acceptability for non-physician clinician involvement, increasing the capacity of non-physician clinicians could enable uptake of ACP in primary care.


Asunto(s)
Planificación Anticipada de Atención/organización & administración , Actitud del Personal de Salud , Comunicación , Médicos de Atención Primaria , Adulto , Canadá , Familia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Relaciones Médico-Paciente , Atención Primaria de Salud , Encuestas y Cuestionarios
9.
Small ; 15(49): e1904746, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31670469

RESUMEN

Today's perovskite solar cells (PSCs) mostly use components, such as organic hole conductors or noble metal back contacts, that are very expensive or cause degradation of their photovoltaic performance. For future large-scale deployment of PSCs, these components need to be replaced with cost-effective and robust ones that maintain high efficiency while ascertaining long-term operational stability. Here, a simple and low-cost PSC architecture employing dopant-free TiO2 and CuSCN as the electron and hole conductor, respectively, is introduced while a graphitic carbon layer deposited at room temperature serves as the back electrical contact. The resulting PSCs show efficiencies exceeding 18% under standard AM 1.5 solar illumination and retain ≈95% of their initial efficiencies for >2000 h at the maximum power point under full-sun illumination at 60 °C. In addition, the CuSCN/carbon-based PSCs exhibit remarkable stability under ultraviolet irradiance for >1000 h while under similar conditions, the standard spiro-MeOTAD/Au based devices degrade severely.

10.
Langmuir ; 35(20): 6493-6505, 2019 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-30196703

RESUMEN

From an ingenious methodology for obtaining monodispersity, digestive ripening has advanced to become an outstanding solution-based synthesis route to realizing various bimetallic heterostructures. This feature article attempts to provide an overview of the various facets of the codigestive ripening process and the array of heterostructures that could be achieved by this technique. We briefly discuss the mechanism of digestive ripening in the case of monometallic elements and use that understanding to elucidate the mechanism of the less well established codigestive ripening strategy for designing bimetallic nanostructures. The systems studied by our group in the past decade for the fabrication of diverse heterostructures are highlighted in this article. The exploitation of digestive ripening to realize monodisperse bimetallic nanostructures by several other groups is also featured. In addition to digestive ripening agents, the significance of tuning various reaction parameters and its consequences on the final structure and morphology have also been discussed. Additionally, efforts based on theoretical studies to gain insight into the factors which dominate the mechanism of the digestive ripening process have also been covered. This article is a contribution to the understanding of the codigestive ripening methodology and a demonstration of its tremendous potential in achieving the desired bimetallic heteronanostructures.

11.
Mol Biol Rep ; 46(5): 5103-5112, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31290055

RESUMEN

The therapeutic application of recombinant proteins is limited due to their inherent structural complexity. Additionally, screening of therapeutic potential of protein products requires an appropriate testing platform to achieve biological relevance. Fabrication of three dimensional cultures bridges the gap between in vitro based monolayer cultures and clinical applications. In this perspective, glioblastoma U-87 MG and breast cancer MCF7 spheroids were generated to assess the therapeutic prospect of recombinant PTEN protein. PTEN bound to silver nanoclusters was encapsulated within PEG coating, which resulted in fabrication of spherical nanocarriers named as PTEN-nanocomposites. Internalization of PTEN-nanocomposites in the spheroids was confirmed by confocal microscopy. Upon uptake, PTEN-nanocomposites led to modulation of cyclins and apoptosis gene regulators culminating in cell cycle arrest and reduced cell viability as confirmed by calcein-AM/PI dual staining and alamar blue assay. Further, combination of tamoxifen and PTEN-nanocomposites on U-87 MG spheroids resulted in two-fold reduction of drug dosage. The study revealed that the monolayer culture results translated to the 3D culture as well, however higher dose of the recombinant PTEN was required for the spheroid system. The anti-proliferative role of PTEN-nanocomposites in a complex 3D environment augments its biological implication and paves the way for recombinant PTEN based therapeutic applications.


Asunto(s)
Fosfohidrolasa PTEN/farmacología , Polietilenglicoles/química , Esferoides Celulares/citología , Tamoxifeno/farmacología , Técnicas de Cultivo de Célula , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Sinergismo Farmacológico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Células MCF-7 , Nanopartículas del Metal , Microscopía Confocal , Nanocompuestos , Fosfohidrolasa PTEN/química , Fosfohidrolasa PTEN/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacología , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/metabolismo
12.
Small ; 14(36): e1802033, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30091843

RESUMEN

Efficiencies >20% are obtained from the perovskite solar cells (PSCs) employing Cs+ and Rb+ based perovskite compositions; therefore, it is important to understand the effect of these inorganic cations specifically Rb+ on the properties of perovskite structures. Here the influence of Cs+ and Rb+ is elucidated on the structural, morphological, and photophysical properties of perovskite structures and the photovoltaic performances of resulting PSCs. Structural, photoluminescence (PL), and external quantum efficiency studies establish the incorporation of Cs+ (x < 10%) but amply rule out the possibility of Rb-incorporation into the MAPbI3 (MA = CH3 NH3+ ) lattice. Moreover, morphological studies and time-resolved PL show that both Cs+ and Rb+ detrimentally affect the surface coverage of MAPbI3 layers and charge-carrier dynamics, respectively, by influencing nucleation density and by inducing nonradiative recombination. In addition, differential scanning calorimetry shows that the transition from orthorhombic to tetragonal phase occurring around 160 K requires more thermal energy for the Cs-containing MAPbI3 systems compared to the pristine MAPbI3 . Investigation including mixed halide (I/Br) and mixed cation A-cation based compositions further confirms the absence of Rb+ from the 3D-perovskite lattice. The fundamental insights gained through this work will be of great significance to further understand highly promising perovskite compositions.

13.
Biotechnol Bioeng ; 115(5): 1116-1127, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29384195

RESUMEN

Amalgamation of delivery and tracking of therapeutically relevant moieties on a single platform is made possible by the application of metal nanoclusters, an innovative class of luminescent nanomaterials. Metal nanoclusters, possessing molecule-like attributes, display extraordinary size and shape tunable properties befitting theranostic applications. Herein, we report successful assembly of therapeutically significant phosphatase protein PTEN and fluorescent lysozyme-stabilized silver nanoclusters to accomplish delivery and tracking of the protein. Down-regulation of PTEN perturbs the cellular networking leading to copious pathological conditions. The integration of purified recombinant PTEN with silver nanoclusters was evaluated by fluorescence spectroscopy study. A key feature of this study is the use of polyethylene glycol coating that allows fabrication of the assembly into spherical nanocomposites as characterized by transmission electron microscope along with retention of both optical functionality of the cluster and biological activity of the protein. Prior to cellular application, the functional integrity of PTEN in the composite was determined in vitro, by enzymatic assay employing para-nitrophenylphosphate as substrate. Cellular internalization of the cargo was studied by confocal microscopy and flow cytometry analysis. The efficacy of the payload on modulation of cellular signaling was assessed on cell lines that expressed PTEN differentially. PTEN null U-87 MG and PTEN expressing MCF7 cell lines displayed successful alteration of AKT and FAK signaling proteins culminating in cell cycle arrest and reduced wound healing capacity. A dose dependent reduction in cell proliferation of MCF7 cells was achieved. For U-87 MG, treatment with the payload resulted in chemosensitization toward anti-cancer drug erlotinib. Thus, PEG coated GST-PTEN loaded silver nanoclusters serves as a comprehensive system encompassing cellular imaging and protein delivery with potential biomedical implications.


Asunto(s)
Muramidasa/metabolismo , Neoplasias/diagnóstico por imagen , Neoplasias/diagnóstico , Fosfohidrolasa PTEN/metabolismo , Plata/metabolismo , Nanomedicina Teranóstica/métodos , Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Transmisión de Enfermedad Infecciosa , Clorhidrato de Erlotinib/farmacología , Citometría de Flujo , Humanos , Células MCF-7 , Microscopía Confocal , Modelos Biológicos , Espectrometría de Fluorescencia
14.
Prep Biochem Biotechnol ; 48(2): 128-135, 2018 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-29194006

RESUMEN

A paradigm shift toward fusion proteins to render multiple functionalities and applications on a single platform has been incurred in enzyme based diagnosis. Herein, we report development and systematic characterizations of glutathione-S-transferase (GST) and human lactate dehydrogenase A (hLDHA) in a fusion protein (GST-hLDHA) to achieve functional activities of GST and hLDHA simultaneously. The GST-pGEX-4T-2 vector system was used for cloning and purification of hLDHA, utilizing the affinity based interaction between GST and GSH in column chromatography. Bacterially purified protein was subjected to the Western blot analysis and structural analysis by circular dichroism spectroscopy, which revealed intact structural framework of the fusion construct. Kinetic characterization of the fusion GST-hLDHA protein toward GSH and NADH, suggested retention of functional activities of GST and hLDHA in fused protein as indicated by the kinetic parameters km and kcat/km. Further analysis of effect of temperature and pH on GST-hLDHA activity revealed maximum activity around human physiological conditions (37°C and pH 8). Preservation of the structural and functional characteristics of the fusion enzyme paves the way for potential application for the detection of NADH and GSH in conjunction as biomarkers for cancer diagnosis.


Asunto(s)
Glutatión Transferasa/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Clonación Molecular , Glutatión/metabolismo , Glutatión Transferasa/genética , Humanos , Concentración de Iones de Hidrógeno , Isoenzimas/genética , Isoenzimas/metabolismo , Cinética , L-Lactato Deshidrogenasa/genética , Lactato Deshidrogenasa 5 , NAD/metabolismo , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Temperatura
15.
Transfusion ; 57(12): 2928-2936, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28944484

RESUMEN

BACKGROUND: Patients with blood, immune, or metabolic diseases may require a stem cell transplant as part of their treatment. However, 70% of patients do not have a suitable human leukocyte antigen match in their family, and need an unrelated donor. Individuals can register as potential donors at stem cell drives, where they provide consent and a tissue sample for human leukocyte antigen typing. The ideal donors are young, male, and from a diversity of ethnic backgrounds. However, in Canada, non-Caucasian males ages 17 to 35 years represent only 8.8% of listed donors. STUDY DESIGN AND METHODS: The Stem Cell Club is a non-profit organization founded in 2011 in Canada that aims to augment recruitment of the most needed donors. The initiative published a recruitment toolkit online (www.stemcellclub.ca). Currently, there are 12 chapters at universities across Canada. RESULTS: To date, the Stem Cell Club has recruited 6585 potential registrants, representing 1.63% of donors on Canada's donor-database. Of the recruited registrants, 58.3% were male; 60.3% of males self-reported as non-Caucasian, and 78.5% were ages 17 to 25 years. From 2015 to 2016, the initiative recruited 13.7% of all ethnically diverse males ages 17 to 35 years listed in Canada's donor database. Data from this initiative demonstrate sustainability and performance on key indicators of stem cell drive quality. CONCLUSION: The Stem Cell Club has developed a capacity to recruit 2600 donors annually, with the majority being males with a high degree of ethnic diversity. The initiative enhances the quality of Canada's unrelated donor-database, improving the chances that patients in need of an unrelated donor will find a match for transplant. The Stem Cell Club is a model relevant to recruitment organizations around the world.


Asunto(s)
Donantes de Sangre/provisión & distribución , Selección de Personal/métodos , Donante no Emparentado/provisión & distribución , Femenino , Humanos , Masculino , Selección de Personal/organización & administración , Trasplante de Células Madre
16.
Biotechnol Lett ; 39(10): 1591-1598, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28730426

RESUMEN

OBJECTIVES: To investigate the potential of recombinant phytaspase loaded manganese (Mn) doped zinc sulphide (ZnS) quantum dots embedded chitosan nanoparticles for augmenting cisplatin induced chemotherapy of HeLa cells. RESULTS: The recombinant phytaspase was cloned into bacterial expression vector PGEX-4T-2. The expressed and purified recombinant plant phytaspase protein from Escherichia coli BL21 was immobilized onto the cationic nanocomposite. Confocal microscopy elucidated the delivery of these luminescent nanocomposites inside cervical cancer HeLa cells. A 50% reduction in the viability of HeLa cells was achieved only in the case of phytaspase-nanocomposites-cisplatin combination at a dose of phytaspase (42 nM), nanocomposites (56.3 µg/ml) and cisplatin (0.44 µg/ml). CONCLUSION: Luminescent cationic nanocomposites were developed for intracellular delivery of recombinant phytaspase, which due to its caspase-like activity assisted in substantiating the chemotherapeutic activity of apoptosis inducing drug-cisplatin.


Asunto(s)
Quitosano/química , Cisplatino/farmacología , Puntos Cuánticos/química , Serina Proteasas/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Expresión Génica , Células HeLa , Humanos , Luminiscencia , Microscopía Confocal , Microscopía Electrónica de Transmisión , Nanopartículas , Sulfuros/química , Difracción de Rayos X , Compuestos de Zinc/química
17.
Nano Lett ; 16(11): 7155-7162, 2016 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-27776210

RESUMEN

We report on both the intrinsic and the extrinsic stability of a formamidinium lead bromide [CH(NH2)2PbBr3 = FAPbBr3] perovskite solar cell that yields a high photovoltage. The fabrication of FAPbBr3 devices, displaying an outstanding photovoltage of 1.53 V and a power conversion efficiency of over 8%, was realized by modifying the mesoporous TiO2-FAPbBr3 interface using lithium treatment. Reasons for improved photovoltaic performance were revealed by a combination of techniques, including photothermal deflection absorption spectroscopy (PDS), transient-photovoltage and charge-extraction analysis, and time-integrated and time-resolved photoluminescence. With lithium-treated TiO2 films, PDS reveals that the TiO2-FAPbBr3 interface exhibits low energetic disorder, and the emission dynamics showed that electron injection from the conduction band of FAPbBr3 into that of mesoporous TiO2 is faster than for the untreated scaffold. Moreover, compared to the device with pristine TiO2, the charge carrier recombination rate within a device based on lithium-treated TiO2 film is 1 order of magnitude lower. Importantly, the operational stability of perovskites solar cells examined at a maximum power point revealed that the FAPbBr3 material is intrinsically (under nitrogen) as well as extrinsically (in ambient conditions) stable, as the unsealed devices retained over 95% of the initial efficiency under continuous full sun illumination for 150 h in nitrogen and dry air and 80% in 60% relative humidity (T = ∼60 °C). The demonstration of high photovoltage, a record for FAPbBr3, together with robust stability renders our work of practical significance.

18.
Phys Biol ; 13(6): 066005, 2016 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-27848929

RESUMEN

Cysteine residues (Cys) in the membrane proximal region are common post-translational modification (PTM) sites in transmembrane proteins. Herein, the effects of a highly conserved membrane proximal α-subunit Cys1368 on the diffusion properties of αPS2CßPS integrins are reported. Sequence alignment shows that this cysteine is palmitoylated in human α3 and α6 integrin subunits. Replacing Cys1368 in wild-type integrins with valine (Val1368) putatively blocks a PTM site and alters integrins' ligand binding and diffusion characteristics. Both fluorescence recovery after photobleaching (FRAP) and single particle tracking (SPT) diffusion measurements show Val1368 integrins are more mobile compared to wild-type integrins. Approximately 33% and 8% more Val1368 integrins are mobile as measured by FRAP and SPT, respectively. The mobile Val1368 integrins also exhibit less time-dependent diffusion, as measured by FRAP. Tandem mass spectrometry data suggest that Cys1368 contains a redox or palmitoylation PTM in αPS2CßPS integrins. This membrane proximal Cys may play an important role in the diffusion of other alpha subunits that contain this conserved residue.


Asunto(s)
Cisteína/metabolismo , Cadenas alfa de Integrinas/química , Cadenas alfa de Integrinas/genética , Sustitución de Aminoácidos , Animales , Proteínas Bacterianas/genética , Bioquímica/métodos , Cisteína/química , Difusión , Drosophila/genética , Proteínas de Drosophila/química , Recuperación de Fluorescencia tras Fotoblanqueo/métodos , Cadenas alfa de Integrinas/metabolismo , Proteínas Luminiscentes/genética , Modificación Traduccional de las Proteínas , Valina/química , Valina/metabolismo
19.
Small ; 11(41): 5533-9, 2015 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-26313216

RESUMEN

Highly ordered 1D TiO2 nanotube arrays are fabricated and applied as nanocontainers and electron transporting material in CH3 NH3 PbI3 perovskite solar cells. The optimized device shows a power conversion efficiency of 14.8%, and improved stability under an illumination of 100 mW cm(-2). This is the best result based on 1D TiO2 nanostructures so far.

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