Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 63
Filtrar
1.
J Public Health Manag Pract ; 27 Suppl 1, COVID-19 and Public Health: Looking Back, Moving Forward: S101-S105, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33239571

RESUMEN

Public health laboratories have played a central role in the US response to COVID-19. Since the earliest days, myriad issues have impeded the laboratory community's ability to keep pace with the overwhelming demand for effective tests. In this article, the Association of Public Health Laboratories and a subset of its members examine the response to date and evaluate lessons learned from 4 main categories: testing surges, supplies, staffing, and regulations and policy. Within these categories, the authors offer recommendations intended both to improve the ongoing COVID-19 response and to strengthen planning for future outbreaks.


Asunto(s)
/prevención & control , Brotes de Enfermedades/prevención & control , Guías como Asunto , Ciencia del Laboratorio Clínico/tendencias , Pandemias/prevención & control , Salud Pública/normas , Salud Pública/tendencias , /epidemiología , Predicción , Humanos , Ciencia del Laboratorio Clínico/estadística & datos numéricos , Estados Unidos/epidemiología
2.
Mol Ther Oncolytics ; 18: 149-160, 2020 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-32671190

RESUMEN

Chimeric antigen receptor (CAR)-modified T cells have demonstrated efficacy against B cell leukemias/lymphomas. However, redirecting CAR T cells to malignant T cells is more challenging due to product-specific cis- and trans-activation causing fratricide. Other challenges include the potential for product contamination and T cell aplasia. We expressed non-signaling CARs (NSCARs) in γδ T cells since donor-derived γδ T cells can be used to prevent product contamination, and NSCARs lack signaling/activation domains, but retain antigen-specific tumor cell-targeting capability. As a result, NSCAR targeting requires an alternative cytotoxic mechanism, which can be achieved through utilization of γδ T cells that possess major histocompatibility complex (MHC)-independent cytotoxicity. We designed two distinct NSCARs and demonstrated that they do not enhance tumor-killing by αß T cells, as predicted. However, both CD5-NSCAR- and CD19-NSCAR-modified γδ T cells enhanced cytotoxicity against T and B cell acute lymphoblastic leukemia (T-ALL and B-ALL) cell lines, respectively. CD5-NSCAR expression in γδ T cells resulted in a 60% increase in cytotoxicity of CD5-expressing T-ALL cell lines. CD19-NSCAR-modified γδ T cells exhibited a 350% increase in cytotoxicity against a CD19-expressing B-ALL cell line compared to the cytotoxicity of naive cells. NSCARs may provide a mechanism to enhance antigen-directed anti-tumor cytotoxicity of γδ T cells through the introduction of a high-affinity interaction while avoiding self-activation.

3.
J Phys Med Rehabil ; 2(2): 23-28, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32705088

RESUMEN

Background context: Exercise therapy for low back pain has long been prescribed as one of the initial remedies for back pain. Traditional therapy is completed under a therapist's supervision and consists of lumbar stabilization, aerobic exercise and stretching exercises. Recent studies have explored treating back pain with aerobic exercise such as walking which can be done anywhere and without supervision which is lower cost and easily administered. Purpose: To assess a therapeutic dosage of aerobic exercise that is associated with pain reduction in persons experiencing low back pain. Study design: Case series. Participant description: Sixteen patients entered the study and twelve patients completed the study (mean ± SD: age 51 ± 11 years; weight 89.2 ± 16 kg). Subjects were included if they were ages 18-65, had chronic back pain lasting for more than 3 months and a score of greater than 30% on the Oswestry Low Back Disability Questionnaire. Methods: Subjects underwent a six-week exercise program using the elliptical trainer three times each week. Exercise duration was steadily increased each week for the length of the study. The total cumulative amount of work that coincided with significant reductions in chronic low back pain was then identified. Results: At 4 weeks, pain scores were significantly reduced from baseline (3.2 vs 4.7, p<0.0001). This significant pain reduction corresponded to an average of 30.8 Kcal/kg of body mass in cumulative work performed. Pain was significantly reduced by 21% and 32% on the Oswestry Questionnaire and the PROMIS 29 respectively. Conclusions: These pilot findings suggest that approximately 30.8 kcal/Kg of accumulated physiological work is a therapeutic "dosage" of exercise needed for significant reduction in chronic back pain. Clinicians can begin to use this benchmark for their oversight of rehabilitation programs to determine if an exercise program has been sufficiently intense and long enough in duration for managing their patients with chronic low back pain.

4.
Microbiol Resour Announc ; 9(20)2020 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-32409528

RESUMEN

Picochlorum celeri is a fast-growing marine microalga with high biomass productivity. Here, we report the use of PacBio sequencing to assemble the phased diploid genome of P. celeri.

6.
Int J Cancer ; 147(5): 1405-1418, 2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-31989583

RESUMEN

Progress in rectal cancer therapy has been hindered by the lack of effective disease-specific preclinical models that account for the unique molecular profile and biology of rectal cancer. Thus, we developed complementary patient-derived xenograft (PDX) and subsequent in vitro tumor organoid (PDTO) platforms established from preneoadjuvant therapy rectal cancer specimens to advance personalized care for rectal cancer patients. Multiple endoscopic samples were obtained from 26 Stages 2 and 3 rectal cancer patients prior to receiving 5FU/RT and implanted subcutaneously into NSG mice to generate 15 subcutaneous PDXs. Second passaged xenografts demonstrated 100% correlation with the corresponding human cancer histology with maintained mutational profiles. Individual rectal cancer PDXs reproduced the 5FU/RT response observed in the corresponding human cancers. Similarly, rectal cancer PDTOs reproduced significant heterogeneity in cellular morphology and architecture. PDTO in vitro 5FU/RT treatment response replicated the clinical 5FU/RT neoadjuvant therapy pathologic response observed in the corresponding patient tumors (p < 0.05). The addition of cetuximab to the 5FU/RT regiment was significantly more sensitive in the rectal cancer PDX and PDTOs with wild-type KRAS compared to mutated KRAS (p < 0.05). Considering the close relationship between the patient's cancer and the corresponding PDX/PDTO, rectal cancer patient-derived research platforms represent powerful translational research resources as population-based tools for biomarker discovery and experimental therapy testing. In addition, our findings suggest that cetuximab may enhance RT effectiveness by improved patient selection based on mutational profile in addition to KRAS or by developing a protocol using PDTOs to identify sensitive patients.

7.
Health Secur ; 17(6): 495-503, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31859570

RESUMEN

Biosecurity and biosafety measures are designed to mitigate intentional and accidental biological risks that pose potentially catastrophic consequences to a country's health system, security, and political and economic stability. Unfortunately, biosecurity and biosafety are often under-prioritized nationally, regionally, and globally. Security leaders often deemphasize accidental and deliberate biological threats relative to other challenges to peace and security. Given emerging biological risks, including those associated with rapid technological advances and terrorist and state interest in weapons of mass destruction, biosecurity deserves stronger emphasis in health and security fora. The Global Biosecurity Dialogue (GBD) was initiated to align national and regional donor initiatives toward a common set of measurable targets. The GBD was launched by the Nuclear Threat Initiative (NTI), with support from Global Affairs Canada's Weapons Threat Reduction Program and the Open Philanthropy Project, and in coordination with the government of The Netherlands as the 2018-19 Chair of the Global Health Security Agenda (GHSA) Action Package Prevent-3 (APP3) on Biosafety and Biosecurity. The GBD provides a multisectoral forum for sharing models, enabling new actions to achieve biosecurity-related targets, and promoting biosecurity as an integral component of health security. The GBD has contributed to new national and continent-wide actions, including the African Union and Africa Centres for Disease Control and Prevention's new regional Initiative to Strengthen Biosafety and Biosecurity in Africa. Here we present the GBD as a model for catalyzing action within APP3. We describe how the benefits of this approach could expand to other GHSA Action Packages and international health security initiatives.


Asunto(s)
Bioterrorismo/prevención & control , Contención de Riesgos Biológicos/métodos , Brotes de Enfermedades/prevención & control , Salud Global , Cooperación Internacional , Medidas de Seguridad/organización & administración , Creación de Capacidad/métodos , Creación de Capacidad/organización & administración , Política de Salud , Humanos
9.
Mol Ther ; 26(3): 744-754, 2018 03 07.
Artículo en Inglés | MEDLINE | ID: mdl-29475734

RESUMEN

Epithelial-to-mesenchymal transition (EMT) has been closely linked with therapy resistance and cancer stem cells (CSCs). However, EMT pathways have proven challenging to therapeutically target. MicroRNA 145 (miR-145) targets multiple stem cell transcription factors and its expression is inversely correlated with EMT. Therefore, we hypothesized that miR-145 represents a therapeutic target to reverse snail family transcriptional repressor 1 (SNAI1)-mediated stemness and radiation resistance (RT). Stable expression of SNAI1 in DLD1 and HCT116 cells (DLD1-SNAI1; HCT116-SNAI1) increased expression of Nanog and decreased miR-145 expression compared to control cells. Using a miR-145 luciferase reporter assay, we determined that ectopic SNAI1 expression significantly repressed the miR-145 promoter. DLD1-SNAI1 and HCT116-SNAI1 cells demonstrated decreased RT sensitivity and, conversely, miR-145 replacement significantly enhanced RT sensitivity. Of the five parental colon cancer cell lines, SW620 cells demonstrated relatively high endogenous SNAI1 and low miR-145 levels. In the SW620 cells, miR-145 replacement decreased CSC-related transcription factor expression, spheroid formation, and radiation resistance. In rectal cancer patient-derived xenografts, CSC identified by EpCAM+/aldehyde dehydrogenase (ALDH)+ demonstrated high expression of SNAI1, c-Myc, and Nanog compared with non-CSCs (EpCAM+/ALDH-). Conversely, patient-derived CSCs demonstrated low miR-145 expression levels relative to non-CSCs. These results suggest that the SNAI1:miR-145 pathway represents a novel therapeutic target in colorectal cancer to overcome RT resistance.


Asunto(s)
Neoplasias Colorrectales/genética , MicroARNs/genética , Células Madre Neoplásicas/metabolismo , Tolerancia a Radiación/genética , Factores de Transcripción de la Familia Snail/genética , Biomarcadores , Línea Celular Tumoral , Autorrenovación de las Células/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/radioterapia , Regulación Neoplásica de la Expresión Génica , Humanos , Modelos Biológicos , Fenotipo , Regiones Promotoras Genéticas , Interferencia de ARN , Factores de Transcripción de la Familia Snail/metabolismo
11.
Appl Environ Microbiol ; 82(8): 2494-2505, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26896141

RESUMEN

Managing ecosystems to maintain biodiversity may be one approach to ensuring their dynamic stability, productivity, and delivery of vital services. The applicability of this approach to industrial ecosystems that harness the metabolic activities of microbes has been proposed but has never been tested at relevant scales. We used a tag-sequencing approach with bacterial small subunit rRNA (16S) genes and eukaryotic internal transcribed spacer 2 (ITS2) to measuring the taxonomic composition and diversity of bacteria and eukaryotes in an open pond managed for bioenergy production by microalgae over a year. Periods of high eukaryotic diversity were associated with high and more-stable biomass productivity. In addition, bacterial diversity and eukaryotic diversity were inversely correlated over time, possibly due to their opposite responses to temperature. The results indicate that maintaining diverse communities may be essential to engineering stable and productive bioenergy ecosystems using microorganisms.


Asunto(s)
Bacterias/crecimiento & desarrollo , Biota , Eucariontes/crecimiento & desarrollo , Microbiología Industrial , Microbiología del Agua , Bacterias/clasificación , Bacterias/genética , Análisis por Conglomerados , ADN Ribosómico/química , ADN Ribosómico/genética , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Eucariontes/clasificación , Eucariontes/genética , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN
14.
J Lipid Res ; 56(1): 38-50, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25327529

RESUMEN

Exposure of endothelial cells (ECs) to agents such as oxidized glycerophospholipids (oxGPs) and cytokines, known to accumulate in atherosclerotic lesions, perturbs the expression of hundreds of genes in ECs involved in inflammatory and other biological processes. We hypothesized that microRNAs (miRNAs) are involved in regulating the inflammatory response in human aortic endothelial cells (HAECs) in response to oxGPs and interleukin 1ß (IL-1ß). Using next-generation sequencing and RT-quantitative PCR, we characterized the profile of expressed miRNAs in HAECs pre- and postexposure to oxGPs. Using this data, we identified miR-21-3p and miR-27a-5p to be induced 3- to 4-fold in response to oxGP and IL-1ß treatment compared with control treatment. Transient overexpression of miR-21-3p and miR-27a-5p resulted in the downregulation of 1,253 genes with 922 genes overlapping between the two miRNAs. Gene Ontology functional enrichment analysis predicted that the two miRNAs were involved in the regulation of nuclear factor κB (NF-κB) signaling. Overexpression of these two miRNAs leads to changes in p65 nuclear translocation. Using 3' untranslated region luciferase assay, we identified 20 genes within the NF-κB signaling cascade as putative targets of miRs-21-3p and -27a-5p, implicating these two miRNAs as modulators of NF-κB signaling in ECs.


Asunto(s)
Células Endoteliales/efectos de los fármacos , Interleucina-1beta/farmacología , MicroARNs/genética , Fosfatidilcolinas/farmacología , Transducción de Señal/efectos de los fármacos , Factor de Transcripción ReIA/metabolismo , Regiones no Traducidas 3'/genética , Transporte Activo de Núcleo Celular/efectos de los fármacos , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Células Endoteliales/citología , Células Endoteliales/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Oxidación-Reducción , Fosfatidilcolinas/química , Análisis de Secuencia de ARN , Factor de Transcripción ReIA/genética , Factor de Necrosis Tumoral alfa/farmacología
15.
PLoS One ; 9(9): e107351, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25222706

RESUMEN

Sugarcane is a major crop used for food and bioenergy production. Modern cultivars are hybrids derived from crosses between Saccharum officinarum and Saccharum spontaneum. Hybrid cultivars combine favorable characteristics from ancestral species and contain a genome that is highly polyploid and aneuploid, containing 100-130 chromosomes. These complex genomes represent a huge challenge for molecular studies and for the development of biotechnological tools that can facilitate sugarcane improvement. Here, we describe full-length enriched cDNA libraries for Saccharum officinarum, Saccharum spontaneum, and one hybrid genotype (SP803280) and analyze the set of open reading frames (ORFs) in their genomes (i.e., their ORFeomes). We found 38,195 (19%) sugarcane-specific transcripts that did not match transcripts from other databases. Less than 1.6% of all transcripts were ancestor-specific (i.e., not expressed in SP803280). We also found 78,008 putative new sugarcane transcripts that were absent in the largest sugarcane expressed sequence tag database (SUCEST). Functional annotation showed a high frequency of protein kinases and stress-related proteins. We also detected natural antisense transcript expression, which mapped to 94% of all plant KEGG pathways; however, each genotype showed different pathways enriched in antisense transcripts. Our data appeared to cover 53.2% (17,563 genes) and 46.8% (937 transcription factors) of all sugarcane full-length genes and transcription factors, respectively. This work represents a significant advancement in defining the sugarcane ORFeome and will be useful for protein characterization, single nucleotide polymorphism and splicing variant identification, evolutionary and comparative studies, and sugarcane genome assembly and annotation.


Asunto(s)
Biblioteca de Genes , Sistemas de Lectura Abierta/genética , Saccharum/genética , Cromosomas de las Plantas/genética , Etiquetas de Secuencia Expresada , Genoma de Planta/genética , Genotipo , Saccharum/metabolismo
16.
Public Health Rep ; 128 Suppl 2: 20-33, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23997300

RESUMEN

Beginning in early 2011, the Centers for Disease Control and Prevention and the Association of Public Health Laboratories launched the Laboratory Efficiencies Initiative (LEI) to help public health laboratories (PHLs) and the nation's entire PHL system achieve and maintain sustainability to continue to conduct vital services in the face of unprecedented financial and other pressures. The LEI focuses on stimulating substantial gains in laboratories' operating efficiency and cost efficiency through the adoption of proven and promising management practices. In its first year, the LEI generated a strategic plan and a number of resources that PHL directors can use toward achieving LEI goals. Additionally, the first year saw the formation of a dynamic community of practitioners committed to implementing the LEI strategic plan in coordination with state and local public health executives, program officials, foundations, and other key partners.


Asunto(s)
Laboratorios/organización & administración , Salud Pública/métodos , Centers for Disease Control and Prevention, U.S. , Sistemas de Información en Laboratorio Clínico/organización & administración , Sistemas de Información en Laboratorio Clínico/normas , Ahorro de Costo , Análisis Costo-Beneficio , Eficiencia Organizacional , Planificación en Salud , Humanos , Relaciones Interinstitucionales , Laboratorios/economía , Laboratorios/normas , Salud Pública/economía , Salud Pública/normas , Administración en Salud Pública , Estados Unidos , Recursos Humanos
17.
Cell Rep ; 4(5): 921-30, 2013 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-24012759

RESUMEN

Insulin homeostasis in pancreatic ß cells is now recognized as a critical element in the progression of obesity and type II diabetes (T2D). Proteins that interact with insulin to direct its sequential synthesis, folding, trafficking, and packaging into reserve granules in order to manage release in response to elevated glucose remain largely unknown. Using a conformation-based approach combined with mass spectrometry, we have generated the insulin biosynthetic interaction network (insulin BIN), a proteomic roadmap in the ß cell that describes the sequential interacting partners of insulin along the secretory axis. The insulin BIN revealed an abundant C2 domain-containing transmembrane protein 24 (TMEM24) that manages glucose-stimulated insulin secretion from a reserve pool of granules, a critical event impaired in patients with T2D. The identification of TMEM24 in the context of a comprehensive set of sequential insulin-binding partners provides a molecular description of the insulin secretory pathway in ß cells.


Asunto(s)
Insulina/biosíntesis , Proteínas de la Membrana/metabolismo , Secuencia de Aminoácidos , Animales , Transporte Biológico , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Insulina/metabolismo , Secreción de Insulina , Islotes Pancreáticos/metabolismo , Ratones , Datos de Secuencia Molecular , Obesidad/metabolismo , Transducción de Señal , Fracciones Subcelulares/metabolismo
20.
PLoS Comput Biol ; 4(5): e1000082, 2008 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-18483554

RESUMEN

Reconstructions of cellular metabolism are publicly available for a variety of different microorganisms and some mammalian genomes. To date, these reconstructions are "genome-scale" and strive to include all reactions implied by the genome annotation, as well as those with direct experimental evidence. Clearly, many of the reactions in a genome-scale reconstruction will not be active under particular conditions or in a particular cell type. Methods to tailor these comprehensive genome-scale reconstructions into context-specific networks will aid predictive in silico modeling for a particular situation. We present a method called Gene Inactivity Moderated by Metabolism and Expression (GIMME) to achieve this goal. The GIMME algorithm uses quantitative gene expression data and one or more presupposed metabolic objectives to produce the context-specific reconstruction that is most consistent with the available data. Furthermore, the algorithm provides a quantitative inconsistency score indicating how consistent a set of gene expression data is with a particular metabolic objective. We show that this algorithm produces results consistent with biological experiments and intuition for adaptive evolution of bacteria, rational design of metabolic engineering strains, and human skeletal muscle cells. This work represents progress towards producing constraint-based models of metabolism that are specific to the conditions where the expression profiling data is available.


Asunto(s)
Algoritmos , Perfilación de la Expresión Génica/métodos , Modelos Biológicos , Proteoma/metabolismo , Proyectos de Investigación , Transducción de Señal/fisiología , Simulación por Computador
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...