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1.
Nature ; 601(7893): 348-353, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-35046601

RESUMEN

Nuclear spins were among the first physical platforms to be considered for quantum information processing1,2, because of their exceptional quantum coherence3 and atomic-scale footprint. However, their full potential for quantum computing has not yet been realized, owing to the lack of methods with which to link nuclear qubits within a scalable device combined with multi-qubit operations with sufficient fidelity to sustain fault-tolerant quantum computation. Here we demonstrate universal quantum logic operations using a pair of ion-implanted 31P donor nuclei in a silicon nanoelectronic device. A nuclear two-qubit controlled-Z gate is obtained by imparting a geometric phase to a shared electron spin4, and used to prepare entangled Bell states with fidelities up to 94.2(2.7)%. The quantum operations are precisely characterized using gate set tomography (GST)5, yielding one-qubit average gate fidelities up to 99.95(2)%, two-qubit average gate fidelity of 99.37(11)% and two-qubit preparation/measurement fidelities of 98.95(4)%. These three metrics indicate that nuclear spins in silicon are approaching the performance demanded in fault-tolerant quantum processors6. We then demonstrate entanglement between the two nuclei and the shared electron by producing a Greenberger-Horne-Zeilinger three-qubit state with 92.5(1.0)% fidelity. Because electron spin qubits in semiconductors can be further coupled to other electrons7-9 or physically shuttled across different locations10,11, these results establish a viable route for scalable quantum information processing using donor nuclear and electron spins.

2.
Cell ; 143(7): 1042-4, 2010 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-21183069

RESUMEN

Two papers in this issue of Cell (Paradis-Bleau et al., 2010 and Typas et al., 2010) report that the lipoproteins LpoA and LpoB are required for the synthesis of cell walls in Escherichia coli. Attached to the bacterial outer membrane, these new cell wall components regulate penicillin-binding proteins located at the inner membrane.

3.
Clin Infect Dis ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38913762

RESUMEN

BACKGROUND: In 2023, Tennessee replaced $6.2 M in US Centers for Disease Control and Prevention (CDC) human immunodeficiency virus (HIV) prevention funding with state funds to redirect support away from men who have sex with men (MSM), transgender women (TGW), and heterosexual Black women (HSBW) and to prioritize instead first responders (FR), pregnant people (PP), and survivors of sex trafficking (SST). METHODS: We used a simulation model of HIV disease to compare the clinical impact of Current, the present allocation of condoms, preexposure prophylaxis (PrEP), and HIV testing to CDC priority risk groups (MSM/TGW/HSBW); with Reallocation, funding instead increased HIV testing and linkage of Tennessee-determined priority populations (FR/PP/SST). Key model inputs included baseline condom use (45%-49%), PrEP provision (0.1%-8%), HIV testing frequency (every 2.5-4.8 years), and 30-day HIV care linkage (57%-65%). We assumed Reallocation would reduce condom use (-4%), PrEP provision (-26%), and HIV testing (-47%) in MSM/TGW/HSBW, whereas it would increase HIV testing among FR (+47%) and HIV care linkage (to 100%/90%) among PP/SST. RESULTS: Reallocation would lead to 166 additional HIV transmissions, 190 additional deaths, and 843 life-years lost over 10 years. HIV testing reductions were most influential in sensitivity analysis; even a 24% reduction would result in 287 more deaths compared to Current. With pessimistic assumptions, we projected 1359 additional HIV transmissions, 712 additional deaths, and 2778 life-years lost over 10 years. CONCLUSIONS: Redirecting HIV prevention funding in Tennessee would greatly harm CDC priority populations while conferring minimal benefits to new priority populations.

4.
Clin Infect Dis ; 77(Suppl 7): S528-S535, 2023 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-38118011

RESUMEN

Excessive or inappropriate antimicrobial use contributes to antimicrobial resistance, emphasizing the need to monitor and document the types and quantities of antibiotics used. Thus, data on antimicrobial consumption (AMC) and antimicrobial usage (AMU) are key in informing and promoting judicious use. Our study, conducted during 2019-2023, as part of the CAPTURA project, aimed to understand the state of data availability and quality for AMC and AMU monitoring in Asia. In this article, we describe the challenges and opportunities faced and provide examples of AMU and AMC analysis. World Health Organization (WHO) and country-tailored methodologies and tools were applied to collect retrospective data from 2016 to 2019 in Bangladesh, Bhutan, Laos, Nepal, Pakistan, Papua New Guinea, Sri Lanka, and Timor-Leste. The primary indicator for national AMC was total level of consumption, expressed as total defined daily doses (DDD) per 1000 inhabitants per day for the year or period of data collected. For facility AMC and AMU, the primary indicator was total DDD per admissions per day for the year or period of data collected. Although many countries faced infrastructural challenges in data collection and storage, we managed to collect and analyze AMC data from 6 countries and AMU data from 5. The primary indicators, and additional findings, were visualized to facilitate dissemination and promote the development of action plans. Looking ahead, it is crucial that future initiatives empower each country to establish surveillance infrastructures tailored to their unique contexts, ensuring sustainable progress in the fight against antimicrobial resistance.


Asunto(s)
Antiinfecciosos , Humanos , Estudios Retrospectivos , Antiinfecciosos/uso terapéutico , Antibacterianos/uso terapéutico , Organización Mundial de la Salud , Pakistán
5.
Clin Infect Dis ; 77(Suppl 7): S519-S527, 2023 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-38118005

RESUMEN

BACKGROUND: An effective implementation of antimicrobial resistance (AMR) surveillance projects requires sustainable and multidisciplinary engagement with stakeholders from various backgrounds, interests and aims. The "Capturing Data on Antimicrobial resistance Patterns and Trends in Use in Regions of Asia" (CAPTURA) project, funded by the Fleming Fund, initially targeted 12 countries in South Asia (SA) and Southeast Asia (SEA) to "expand the volume of historical and current data on AMR and antimicrobial usage" and support local agencies through capacity building activities. METHODS: In this article, we focus on early stakeholder engagement activities and present overall statistics on AMR data collated from 72 laboratories across seven countries. This included 2.3 million records of antimicrobial susceptibility testing (AST) data, which were curated, analyzed, and shared back to the facilities for informed decision making. RESULTS: Approximately 98% of the data collated by CAPTURA originated from laboratories based in SA countries. Furthermore, country-wide data were analyzed to identify commonly reported pathogens in each country, followed by descriptions of AST practices and multidrug-resistant (MDR) pathogens. Overall, we found meager adherence to standard guidelines to perform and record AST results, and a significant number of MDR pathogens were reported. CONCLUSIONS: We conclude that close collaboration with the existing national mechanisms for identifying AMR data sources was crucial for the project's success. Although we show a vast retrospective dataset on AMR is available for data sharing in Asia, there remain critical gaps in data generation/management practice and analysis capacity for AMR data at most facilities.


Asunto(s)
Antibacterianos , Farmacorresistencia Bacteriana , Humanos , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Estudios Retrospectivos , Participación de los Interesados , Asia
6.
Clin Infect Dis ; 77(Suppl 7): S549-S559, 2023 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-38118018

RESUMEN

The Institute of Epidemiology, Disease Control and Research (IEDCR) conducts active, case-based national antimicrobial resistance (AMR) surveillance in Bangladesh. The Capturing Data on Antimicrobial Resistance Patterns and Trends in Use in Regions of Asia (CAPTURA) project accessed aggregated retrospective data from non-IEDCR study sites and 9 IEDCR sites to understand the pattern and extent of AMR and to use analyzed data to guide ongoing and future national AMR surveillance in both public and private laboratories. Record-keeping practices, data completeness, quality control, and antimicrobial susceptibility test practices were investigated in all laboratories participating in case-based IEDCR surveillance and laboratory-based CAPTURA sites. All 9 IEDCR laboratories recorded detailed case-based data (n = 16 816) in electronic format for a priority subset of processed laboratory samples. In contrast, most CAPTURA sites (n = 18/33 [54.5%]) used handwritten registers to store data. The CAPTURA sites were characterized by fewer recorded variables (such as patient demographics, clinical history, and laboratory findings) with 1 020 197 individual data, less integration of patient records with the laboratory information system, and nonuniform practice of data recording; however, data were collected from all available clinical samples. The analyses conducted on AMR data collected by IEDCR and CAPTURA in Bangladesh provide current data collection status and highlight opportunities to improve ongoing data collection to strengthen current AMR surveillance system initiatives. We recommend a tailored approach to conduct AMR surveillance in high-burden, resource-limited settings.


Asunto(s)
Antibacterianos , Farmacorresistencia Bacteriana , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bangladesh/epidemiología , Estudios Retrospectivos , Laboratorios
7.
Clin Infect Dis ; 77(Suppl 7): S507-S518, 2023 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-38118007

RESUMEN

Antimicrobial resistance (AMR) is a multifaceted global health problem disproportionately affecting low- and middle-income countries (LMICs). The Capturing data on Antimicrobial resistance Patterns and Trends in Use in Regions of Asia (CAPTURA) project was tasked to expand the volume of AMR and antimicrobial use data in Asia. The CAPTURA project used 2 data-collection streams: facility data and project metadata. Project metadata constituted information collected to map out data sources and assess data quality, while facility data referred to the retrospective data collected from healthcare facilities. A down-selection process, labelled "the funnel approach" by the project, was adopted to use the project metadata in prioritizing and selecting laboratories for retrospective AMR data collection. Moreover, the metadata served as a guide for understanding the AMR data once they were collected. The findings from CAPTURA's metadata add to the current discourse on the limitation of AMR data in LMICs. There is generally a low volume of AMR data generated as there is a lack of microbiology laboratories with sufficient antimicrobial susceptibility testing capacity. Many laboratories in Asia are still capturing data on paper, resulting in scattered or unused data not readily accessible or shareable for analyses. There is also a lack of clinical and epidemiological data captured, impeding interpretation and in-depth understanding of the AMR data. CAPTURA's experience in Asia suggests that there is a wide spectrum of capacity and capability of microbiology laboratories within a country and region. As local AMR surveillance is a crucial instrument to inform context-specific measures to combat AMR, it is important to understand and assess current capacity-building needs while implementing activities to enhance surveillance systems.


Asunto(s)
Antibacterianos , Países en Desarrollo , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Estudios Retrospectivos , Farmacorresistencia Bacteriana , Asia/epidemiología
8.
Prehosp Emerg Care ; : 1-3, 2023 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-37791740

RESUMEN

OBJECTIVES: Helicopter emergency services (HEMS) serve a crucial role in the triage and transport of critically ill patients. Rapid transport to definitive care has become the goal of all prehospital EMS as shorter scene intervals have been associated with decreased mortality. Over the past several years, we have seen a rise in physicians trained in emergency medicine and EMS responding in the prehospital setting in our HEMS region. Our goal is to determine if the presence of EMS physicians on scene calls with HEMS delays time to hospital for patients. METHODS: This retrospective chart review collected on-scene time data from January 2016 to November 2020. Data were collected from our regional HEMS provider database via EMSCharts. We compared the HEMS scene intervals between calls which were serviced by HEMS crews alone, versus those where EMS physicians were present. The Wilcoxon rank-sum test was used to compare these two distributions, and a p-value <0.05 was used to determine statistical significance. RESULTS: We analyzed 1106 scene calls, four of which were excluded as they should have been designated as inter-facility transfers. Our analysis included 1079 scene calls with HEMS crews alone, and 23 scene calls with EMS physicians, with median HEMS scene intervals of 18 min and 19 min, respectively. A Wilcoxon rank-sum test comparing both distributions had a p-value of 0.30 (z= -1.04). CONCLUSION: There was no significant difference between HEMS scene intervals at calls serviced by HEMS crews alone versus those where EMS physicians were present. EMS physician presence was not associated with prolonged HEMS scene intervals.

9.
Proc Biol Sci ; 289(1981): 20220300, 2022 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-36000233

RESUMEN

Rising global temperatures are expected to increase reproductive costs for wildlife as greater thermoregulatory demands interfere with reproductive activities. However, predicting the temperatures at which reproductive performance is negatively impacted remains a significant hurdle. Using a thermoregulatory polygon approach, we derived a reproductive threshold temperature for an Arctic songbird-the snow bunting (Plectrophenax nivalis). We defined this threshold as the temperature at which individuals must reduce activity to suboptimal levels (i.e. less than four-time basal metabolic rate) to sustain nestling provisioning and avoid overheating. We then compared this threshold to operative temperatures recorded at high (82° N) and low (64° N) Arctic sites to estimate how heat constraints translate into site-specific impacts on sustained activity level. We predict buntings would become behaviourally constrained at operative temperatures above 11.7°C, whereupon they must reduce provisioning rates to avoid overheating. Low-Arctic sites had larger fluctuations in solar radiation, consistently producing daily periods when operative temperatures exceeded 11.7°C. However, high-latitude birds faced entire, consecutive days when parents would be unable to sustain required provisioning rates. These data indicate that Arctic warming is probably already disrupting the breeding performance of cold-specialist birds and suggests counterintuitive and severe negative impacts of warming at higher latitude breeding locations.


Asunto(s)
Pájaros Cantores , Animales , Regiones Árticas , Respuesta al Choque Térmico , Reproducción , Temperatura
10.
Phys Rev Lett ; 129(15): 150502, 2022 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-36269974

RESUMEN

The performance of quantum gates is often assessed using some form of randomized benchmarking. However, the existing methods become infeasible for more than approximately five qubits. Here we show how to use a simple and customizable class of circuits-randomized mirror circuits-to perform scalable, robust, and flexible randomized benchmarking of Clifford gates. We show that this technique approximately estimates the infidelity of an average many-qubit logic layer, and we use simulations of up to 225 qubits with physically realistic error rates in the range 0.1%-1% to demonstrate its scalability. We then use up to 16 physical qubits of a cloud quantum computing platform to demonstrate that our technique can reveal and quantify crosstalk errors in many-qubit circuits.

11.
Am J Public Health ; 112(12): 1721-1725, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36302220

RESUMEN

Vaccination remains key to reducing the risk of COVID-19-related severe illness and death. Because of historic medical exclusion and barriers to access, Black communities have had lower rates of COVID-19 vaccination than White communities. We describe the efforts of an academic medical institution to implement community-based COVID-19 vaccine clinics in medically underserved neighborhoods in Philadelphia, Pennsylvania. Over a 13-month period (April 2021-April 2022), the initiative delivered 9038 vaccine doses to community members, a majority of whom (57%) identified as Black. (Am J Public Health. 2022;112(12):1721-1725. https://doi.org/10.2105/AJPH.2022.307030).


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Humanos , Área sin Atención Médica , COVID-19/epidemiología , COVID-19/prevención & control , Philadelphia/epidemiología , Vacunación
12.
Am J Physiol Regul Integr Comp Physiol ; 320(3): R362-R376, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33356878

RESUMEN

Migratory birds may benefit from diets rich in polyunsaturated fatty acids (PUFAs) that could improve exercise performance. Previous investigations suggest that different types of birds may respond differently to PUFA. We established muscle myocyte cell culture models from muscle satellite cells of a migratory passerine songbird (yellow-rumped warbler, Setophaga coronata coronata) and a nonpasserine shorebird (sanderling, Calidris alba). We differentiated and treated avian myotubes and immortalized murine C2C12 myotubes with n-3 PUFA docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and with monounsaturated oleic acid (OA) to compare effects on aerobic performance, metabolic enzyme activities, key fatty acid (FA) transporters, and expression of peroxisome proliferator-activated receptors (PPARs). Sanderling and C2C12 myotubes increased expression of PPARs with n-3 PUFA treatments, whereas expression was unchanged in yellow-rumped warblers. Both sanderlings and yellow-rumped warblers increased expression of fatty acid transporters, whereas C2C12 cells decreased expression following n-3 PUFA treatments. Only yellow-rumped warbler myotubes increased expression of some metabolic enzymes, whereas the sanderling and C2C12 cells were unchanged. PUFA supplementation in C2C12 myotubes increased mitochondrial respiratory chain efficiency, whereas sanderlings increased proton leak-associated respiration and maximal respiration (measurements were not made in warblers). This research indicates that songbirds and shorebirds respond differently to n-3 PUFA and provides support for the hypothesis that n-3 PUFA increase the aerobic capacity of migrant shorebird muscle, which may improve overall endurance flight performance.


Asunto(s)
Ácidos Docosahexaenoicos/farmacología , Ácido Eicosapentaenoico/farmacología , Metabolismo Energético/efectos de los fármacos , Fibras Musculares Esqueléticas/efectos de los fármacos , Ácido Oléico/farmacología , Pájaros Cantores/metabolismo , Animales , Conducta Animal , Línea Celular , Proteínas de Transporte de Ácidos Grasos/genética , Proteínas de Transporte de Ácidos Grasos/metabolismo , Femenino , Vuelo Animal , Masculino , Ratones , Mitocondrias Musculares/efectos de los fármacos , Mitocondrias Musculares/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Receptores Activados del Proliferador del Peroxisoma/genética , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Especificidad de la Especie
13.
Biol Lett ; 17(8): 20210200, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34403643

RESUMEN

Migratory birds experience bouts of muscle growth and depletion as they prepare for, and undertake prolonged flight. Our studies of migratory bird muscle physiology in vitro led to the discovery that sanderling (Calidris alba) muscle satellite cells proliferate more rapidly than other normal cell lines. Here we determined the proliferation rate of muscle satellite cells isolated from five migratory species (sanderling; ruff, Calidris pugnax; western sandpiper, Calidris mauri; yellow-rumped warbler, Setophaga coronata; Swainson's thrush, Catharus ustulatus) from two families (shorebirds and songbirds) and with different migratory strategies. Ruff and sanderling satellite cells exhibited rapid proliferation, with population doubling times of 9.3 ± 1.3 and 11.4 ± 2 h, whereas the remaining species' cell doubling times were greater than or equal to 24 h. The results indicate that the rapid proliferation of satellite cells is not associated with total migration distance but may be related to flight bout duration and interact with lifespan.


Asunto(s)
Charadriiformes , Pájaros Cantores , Migración Animal , Animales , Proliferación Celular , Humanos , Músculos
14.
Prehosp Emerg Care ; 25(3): 438-440, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32437217

RESUMEN

We report a rare but serious complication of needle thoracostomy, penetration of the myocardium. Needle thoracostomy is typically performed in the prehospital setting or upon arrival in the emergency department for suspected tension pneumothorax. Needle decompression is generally taught and done anteriorly, in the 2nd intercostal space on the midclavicular line (MCL). An alternative approach is laterally, along the anterior axillary line (AAL) in the 4th intercostal space. Our case supports prior literature that the anterior MCL location has a low rate of efficacy to decompress the chest, as well as a high rate of complications. We recommend performing needle decompression laterally at the AAL whether in the field or in the emergency department.


Asunto(s)
Servicios Médicos de Urgencia , Neumotórax , Humanos , Miocardio , Agujas , Neumotórax/etiología , Toracostomía
15.
J Bacteriol ; 202(4)2020 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-31767777

RESUMEN

Bacteria have a variety of mechanisms for adapting to environmental perturbations. Changes in oxygen availability result in a switch between aerobic and anaerobic respiration, whereas iron limitation may lead to siderophore secretion. In addition to metabolic adaptations, many organisms respond by altering their cell shape. Caulobacter crescentus, when grown under phosphate-limiting conditions, dramatically elongates its polar stalk appendage. The stalk is hypothesized to facilitate phosphate uptake; however, the mechanistic details of stalk synthesis are not well characterized. We used a chemical mutagenesis approach to isolate and characterize stalk-deficient mutants, one of which had two mutations in the phosphomannose isomerase gene (manA) that were necessary and sufficient to inhibit stalk elongation. Transcription of the pho regulon was unaffected in the manA mutant; therefore, ManA plays a unique regulatory role in stalk synthesis. The mutant ManA had reduced enzymatic activity, resulting in a 5-fold increase in the intracellular fructose 6-phosphate/mannose 6-phosphate ratio. This metabolic imbalance impaired the synthesis of cellular envelope components derived from mannose 6-phosphate, namely, lipopolysaccharide O-antigen and exopolysaccharide. Furthermore, the manA mutations prevented C. crescentus cells from efficiently entering stationary phase. Deletion of the stationary-phase response regulator gene spdR inhibited stalk elongation in wild-type cells, while overproduction of the alarmone ppGpp, which triggers growth arrest and stationary-phase entry, increased stalk length in the manA mutant strain. These results demonstrate that sugar-phosphate metabolism regulates stalk elongation independently of phosphate starvation.IMPORTANCE Metabolic control of bacterial cell shape is an important mechanism for adapting to environmental perturbations. Caulobacter crescentus dramatically elongates its polar stalk appendage in response to phosphate starvation. To investigate the mechanism of this morphological adaptation, we isolated stalk-deficient mutants, one of which had mutations in the phosphomannose isomerase gene (manA) that blocked stalk elongation, despite normal activation of the phosphate starvation response. The mutant ManA resulted in an imbalance in sugar-phosphate concentrations, which had effects on the synthesis of cellular envelope components and entry into stationary phase. Due to the interconnectivity of metabolic pathways, our findings may suggest more generally that the modulation of bacterial cell shape involves the regulation of growth phase and the synthesis of cellular building blocks.


Asunto(s)
Caulobacter crescentus/metabolismo , Manosa-6-Fosfato Isomerasa/fisiología , Fosfatos/metabolismo , Azúcares/metabolismo , Caulobacter crescentus/genética , Caulobacter crescentus/crecimiento & desarrollo , Manosa-6-Fosfato Isomerasa/genética , Redes y Vías Metabólicas , Mutación , Polimorfismo de Nucleótido Simple
16.
Mol Microbiol ; 112(1): 233-248, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31022322

RESUMEN

Peptidoglycan (PG) is a highly cross-linked polysaccharide that encases bacteria, resists the effects of turgor and confers cell shape. PG precursors are translocated across the cytoplasmic membrane by the lipid carrier undecaprenyl phosphate (Und-P) where they are incorporated into the PG superstructure. Previously, we found that one of our Escherichia coli laboratory strains (CS109) harbors a missense mutation in uppS, which encodes an enzymatically defective Und-P(P) synthase. Here, we show that CS109 cells lacking the bifunctional aPBP PBP1B (penicillin binding protein 1B) lyse during exponential growth at elevated temperature. PBP1B lysis was reversed by: (i) reintroducing wild-type uppS, (ii) increasing the availability of PG precursors or (iii) overproducing PBP1A, a related bifunctional PG synthase. In addition, inhibiting the catalytic activity of PBP2 or PBP3, two monofunctional bPBPs, caused CS109 cells to lyse. Limiting the precursors required for Und-P synthesis in MG1655, which harbors a wild-type allele of uppS, also promoted lysis in mutants lacking PBP1B or bPBP activity. Thus, simultaneous inhibition of Und-P production and PG synthases provokes a synergistic response that leads to cell lysis. These findings suggest a biological connection that could be exploited in combination therapies.


Asunto(s)
Proteínas de Unión a las Penicilinas/metabolismo , Fosfatos de Poliisoprenilo/metabolismo , División Celular , Pared Celular/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Regulación Bacteriana de la Expresión Génica/genética , Proteínas de Unión a las Penicilinas/antagonistas & inhibidores , Peptidoglicano/metabolismo , Peptidoglicano Glicosiltransferasa/metabolismo , Fosfatos de Poliisoprenilo/antagonistas & inhibidores , D-Ala-D-Ala Carboxipeptidasa de Tipo Serina/química
17.
J Neuroinflammation ; 17(1): 32, 2020 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-31973732

RESUMEN

Following publication of the original article, the authors noticed missing labels in Fig. 1a.

18.
J Neuroinflammation ; 16(1): 135, 2019 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-31272467

RESUMEN

BACKGROUND: Conditional ablation of the Smarca5 gene in mice severely impairs the postnatal growth of the cerebellum and causes an ataxic phenotype. Comparative gene expression studies indicated that complement-related proteins were upregulated in the cerebellum of Smarca5 mutant mice. Complement proteins play critical roles within innate immune signaling pathways and, in the brain, are produced by glial cells under both normal and pathological conditions. The C3 complement protein-derived signaling peptide, C3a, has been implicated in contributing to both tissue damage and repair in conditions such as multiple sclerosis and stroke. Here, we investigated whether C3a receptor (C3aR) signaling promoted damage or repair in the developing cerebellum of Smarca5 mutant mice. METHODS: Brain and cerebellum lysates from single Smarca5 conditional knockout (Smarca5 cKO) mice, C3aR1 KO mice, or double mutant mice were used for qRT-PCR and immunoblotting to assess the contribution of C3aR to the Smarca5 cKO brain pathology. Immunohistochemistry was used to characterize alterations to astroglia and phagocyte cells in the developing cerebellum of each of the genotypes. RESULTS: C3aR signaling was observed to limit gliosis and promote granule neuron survival during postnatal cerebellar development. In Smarca5 cKO mice, disorganized astroglia with increased GFAP expression develops concurrently with cerebellar granule neuron loss and phagocyte invasion over the first 10 days following birth. Potential ligand precursors of C3aR-VGF and C3-were found to have upregulated expression and/or altered processing during this time. Phagocytes (microglia and macrophages) in both the control and Smarca5 mutant mice were the only cells observed to express C3aR. Loss of C3aR in the Smarca5 cKO cerebellum resulted in increased numbers of apoptotic cells and early phagocyte invasion into the external granule cell layer, as well as an exacerbated disorganization of the Bergmann glia. The loss of C3aR expression also attenuated an increase in the expression of the efferocytosis-related protein, MerTK, whose transcript was upregulated ~ 2.5-fold in the Smarca5 mutant cerebellum at P10. CONCLUSIONS: This data indicates that C3aR can play an important role in limiting astrogliosis and regulating phagocyte phenotypes following developmental cell loss in the brain.


Asunto(s)
Cerebelo/metabolismo , Gliosis/metabolismo , Trastornos del Neurodesarrollo/metabolismo , Receptores Acoplados a Proteínas G/deficiencia , Transducción de Señal/fisiología , Adenosina Trifosfatasas/deficiencia , Adenosina Trifosfatasas/genética , Secuencia de Aminoácidos , Animales , Cerebelo/patología , Proteínas Cromosómicas no Histona/deficiencia , Proteínas Cromosómicas no Histona/genética , Gliosis/genética , Gliosis/patología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Trastornos del Neurodesarrollo/genética , Trastornos del Neurodesarrollo/patología , Receptores Acoplados a Proteínas G/genética
19.
Phys Rev Lett ; 123(3): 030503, 2019 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-31386463

RESUMEN

Benchmarking methods that can be adapted to multiqubit systems are essential for assessing the overall or "holistic" performance of nascent quantum processors. The current industry standard is Clifford randomized benchmarking (RB), which measures a single error rate that quantifies overall performance. But, scaling Clifford RB to many qubits is surprisingly hard. It has only been performed on one, two, and three qubits as of this writing. This reflects a fundamental inefficiency in Clifford RB: the n-qubit Clifford gates at its core have to be compiled into large circuits over the one- and two-qubit gates native to a device. As n grows, the quality of these Clifford gates quickly degrades, making Clifford RB impractical at relatively low n. In this Letter, we propose a direct RB protocol that mostly avoids compiling. Instead, it uses random circuits over the native gates in a device, which are seeded by an initial layer of Clifford-like randomization. We demonstrate this protocol experimentally on two to five qubits using the publicly available ibmqx5. We believe this to be the greatest number of qubits holistically benchmarked, and this was achieved on a freely available device without any special tuning up. Our protocol retains the simplicity and convenient properties of Clifford RB: it estimates an error rate from an exponential decay. But, it can be extended to processors with more qubits-we present simulations on 10+ qubits-and it reports a more directly informative and flexible error rate than the one reported by Clifford RB. We show how to use this flexibility to measure separate error rates for distinct sets of gates, and we use this method to estimate the average error rate of a set of cnot gates.

20.
J Bacteriol ; 200(13)2018 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-29686141

RESUMEN

While screening the Pfam database for novel peptidoglycan (PG) binding modules, we identified the OapA domain, which is annotated as a LysM-like domain. LysM domains bind PG and mediate localization to the septal ring. In the Gram-negative bacterium Escherichia coli, an OapA domain is present in YtfB, an inner membrane protein of unknown function but whose overproduction causes cells to filament. Together, these observations suggested that YtfB directly affects cell division, most likely through its OapA domain. Here, we show that YtfB accumulates at the septal ring and that its action requires the division-initiating protein FtsZ and, to a lesser extent, ZipA, an early recruit to the septalsome. While the loss of YtfB had no discernible impact, a mutant lacking both YtfB and DedD (a known cell division protein) grew as filamentous cells. The YtfB OapA domain by itself also localized to sites of division, and this localization was enhanced by the presence of denuded PGs. Finally, the OapA domain bound PG, though binding did not depend on the formation of denuded glycans. Collectively, our findings demonstrate that YtfB is a cell division protein whose function is related to cell wall hydrolases.IMPORTANCE All living cells must divide in order to thrive. In bacteria, this involves the coordinated activities of a large number of proteins that work in concert to constrict the cell. Knowing which proteins contribute to this process and how they function is fundamental. Here, we identify a new member of the cell division apparatus in the Gram-negative bacterium Escherichia coli whose function is related to the generation of a transient cell wall structure. These findings deepen our understanding of bacterial cell division.


Asunto(s)
Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/metabolismo , División Celular , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Escherichia coli/citología , Escherichia coli/metabolismo , Proteínas de Ciclo Celular/genética , Pared Celular/genética , Pared Celular/metabolismo , Escherichia coli/química , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Peptidoglicano/metabolismo , Dominios Proteicos
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