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61.
Tomá? Sieger Cecilia Bonnet Tereza Serranová Ji?í Wild Daniel Novák Filip R??i?ka Du?an Urgo?ík Ev?en R??i?ka Bertrand Gaymard Robert Jech 《PloS one》2013,8(11)
The oculomotor role of the basal ganglia has been supported by extensive evidence, although their role in scanning eye movements is poorly understood. Nineteen Parkinsońs disease patients, which underwent implantation of deep brain stimulation electrodes, were investigated with simultaneous intraoperative microelectrode recordings and single channel electrooculography in a scanning eye movement task by viewing a series of colored pictures selected from the International Affective Picture System. Four patients additionally underwent a visually guided saccade task. Microelectrode recordings were analyzed selectively from the subthalamic nucleus, substantia nigra pars reticulata and from the globus pallidus by the WaveClus program which allowed for detection and sorting of individual neurons. The relationship between neuronal firing rate and eye movements was studied by crosscorrelation analysis. Out of 183 neurons that were detected, 130 were found in the subthalamic nucleus, 30 in the substantia nigra and 23 in the globus pallidus. Twenty percent of the neurons in each of these structures showed eye movement-related activity. Neurons related to scanning eye movements were mostly unrelated to the visually guided saccades. We conclude that a relatively large number of basal ganglia neurons are involved in eye motion control. Surprisingly, neurons related to scanning eye movements differed from neurons activated during saccades suggesting functional specialization and segregation of both systems for eye movement control. 相似文献
62.
Szymon ??ski Henrik Lindén Tom Tetzlaff Klas H. Pettersen Gaute T. Einevoll 《PLoS computational biology》2013,9(7)
Despite its century-old use, the interpretation of local field potentials (LFPs), the low-frequency part of electrical signals recorded in the brain, is still debated. In cortex the LFP appears to mainly stem from transmembrane neuronal currents following synaptic input, and obvious questions regarding the ‘locality’ of the LFP are: What is the size of the signal-generating region, i.e., the spatial reach, around a recording contact? How far does the LFP signal extend outside a synaptically activated neuronal population? And how do the answers depend on the temporal frequency of the LFP signal? Experimental inquiries have given conflicting results, and we here pursue a modeling approach based on a well-established biophysical forward-modeling scheme incorporating detailed reconstructed neuronal morphologies in precise calculations of population LFPs including thousands of neurons. The two key factors determining the frequency dependence of LFP are the spatial decay of the single-neuron LFP contribution and the conversion of synaptic input correlations into correlations between single-neuron LFP contributions. Both factors are seen to give low-pass filtering of the LFP signal power. For uncorrelated input only the first factor is relevant, and here a modest reduction (<50%) in the spatial reach is observed for higher frequencies (>100 Hz) compared to the near-DC () value of about . Much larger frequency-dependent effects are seen when populations of pyramidal neurons receive correlated and spatially asymmetric inputs: the low-frequency () LFP power can here be an order of magnitude or more larger than at 60 Hz. Moreover, the low-frequency LFP components have larger spatial reach and extend further outside the active population than high-frequency components. Further, the spatial LFP profiles for such populations typically span the full vertical extent of the dendrites of neurons in the population. Our numerical findings are backed up by an intuitive simplified model for the generation of population LFP. 相似文献
63.
Ya-Ping Ko Annemarie Kuipers Claudia M. Freitag Ilse Jongerius Eva Medina Willemien J. van Rooijen András N. Spaan Kok P. M. van Kessel Magnus H??k Suzan H. M. Rooijakkers 《PLoS pathogens》2013,9(12)
Upon contact with human plasma, bacteria are rapidly recognized by the complement system that labels their surface for uptake and clearance by phagocytic cells. Staphylococcus aureus secretes the 16 kD Extracellular fibrinogen binding protein (Efb) that binds two different plasma proteins using separate domains: the Efb N-terminus binds to fibrinogen, while the C-terminus binds complement C3. In this study, we show that Efb blocks phagocytosis of S. aureus by human neutrophils. In vitro, we demonstrate that Efb blocks phagocytosis in plasma and in human whole blood. Using a mouse peritonitis model we show that Efb effectively blocks phagocytosis in vivo, either as a purified protein or when produced endogenously by S. aureus. Mutational analysis revealed that Efb requires both its fibrinogen and complement binding residues for phagocytic escape. Using confocal and transmission electron microscopy we show that Efb attracts fibrinogen to the surface of complement-labeled S. aureus generating a ‘capsule’-like shield. This thick layer of fibrinogen shields both surface-bound C3b and antibodies from recognition by phagocytic receptors. This information is critical for future vaccination attempts, since opsonizing antibodies may not function in the presence of Efb. Altogether we discover that Efb from S. aureus uniquely escapes phagocytosis by forming a bridge between a complement and coagulation protein. 相似文献
64.
Insect flight is regulated by various sensory inputs and neuromodulatory circuits which function in synchrony to control and fine-tune the final behavioral outcome. The cellular and molecular bases of flight neuromodulatory circuits are not well defined. In Drosophila melanogaster, it is known that neuronal IP3 receptor mediated Ca2+ signaling and store-operated Ca2+ entry (SOCE) are required for air-puff stimulated adult flight. However, G-protein coupled receptors (GPCRs) that activate intracellular Ca2+ signaling in the context of flight are unknown in Drosophila. We performed a genetic RNAi screen to identify GPCRs that regulate flight by activating the IP3 receptor. Among the 108 GPCRs screened, we discovered 5 IP3/Ca2+ linked GPCRs that are necessary for maintenance of air-puff stimulated flight. Analysis of their temporal requirement established that while some GPCRs are required only during flight circuit development, others are required both in pupal development as well as during adult flight. Interestingly, our study identified the Pigment Dispersing Factor Receptor (PdfR) as a regulator of flight circuit development and as a modulator of acute flight. From the analysis of PdfR expressing neurons relevant for flight and its well-defined roles in other behavioral paradigms, we propose that PdfR signaling functions systemically to integrate multiple sensory inputs and modulate downstream motor behavior. 相似文献
65.
Abdulaziz A. Alsaif Tarique N. Hasan Gowhar Shafi Naveed A. Syed Mohammed A. Alsaif Abdullah H. Al-Assaf Ali A. Alshatwi 《Cancer epidemiology》2013,37(5):762-766
Chemotherapy has been used widely to treat cancer, both as a systemic therapy and as a local treatment. Unfortunately, many types of cancer are still refractory to chemotherapy. The mechanisms of anticancer drug resistance have been extensively explored but have not been fully characterized. This study analyzed the occurrences of polymorphism (SNP) in the MDR1 gene in breast cancer patients and determined a possible association with chemotherapy. The study group included one hundred breast carcinoma patients who subsequently received chemotherapy (the regimen generally consisted of commonly used drugs such as cyclophosphamide, adriamycin, 5-fluorouracil, docetaxel and their combinations). Blood samples from 100 healthy individuals are used, as controls were also genotyped for the MDR1 gene. This investigation revealed a significant correlation with response to various regimens of chemotherapy showing a low response to therapy with the CT/TT genotype at (exon 12) 1236 codon (p < 0.001). These findings demonstrate, for the first time, that the polymorphisms in (exon 12) 1236 codon of the MDR1 gene greatly influence the drug response in patients from the Arab population of Saudi Arabia. 相似文献
66.
Chihiro Motozono John J. Miles Zafrul Hasan Hiroyuki Gatanaga Stanley C. Meribe David A. Price Shinichi Oka Andrew K. Sewell Takamasa Ueno 《PloS one》2013,8(6)
Antigen cross-reactivity is an inbuilt feature of the T cell compartment. However, little is known about the flexibility of T cell recognition in the context of genetically variable pathogens such as HIV-1. In this study, we used a combinatorial library containing 24 billion octamer peptides to characterize the cross-reactivity profiles of CD8+ T cells specific for the immunodominant HIV-1 subtype B Nef epitope VY8 (VPLRPMTY) presented by HLA-B*35∶01. In conjunction, we examined naturally occurring antigenic variations within the VY8 epitope. Sequence analysis of plasma viral RNA isolated from 336 HIV-1-infected individuals revealed variability at position (P) 3 and P8 of VY8; Phe at P8, but not Val at P3, was identified as an HLA-B*35∶01-associated polymorphism. VY8-specific T cells generated from several different HIV-1-infected patients showed unique and clonotype-dependent cross-reactivity footprints. Nonetheless, all T cells recognized both the index Leu and mutant Val at P3 equally well. In contrast, competitive titration assays revealed that the Tyr to Phe substitution at P8 reduced T cell recognition by 50–130 fold despite intact peptide binding to HLA-B*35∶01. These findings explain the preferential selection of Phe at the C-terminus of VY8 in HLA-B*35∶01+ individuals and demonstrate that HIV-1 can exploit the limitations of T cell recognition in vivo. 相似文献
67.
We revisit the framework for brain-coupled image search, where the Electroencephalography (EEG) channel under rapid serial visual presentation protocol is used to detect user preferences. Extending previous works on the synergy between content-based image labeling and EEG-based brain-computer interface (BCI), we propose a different perspective on iterative coupling. Previously, the iterations were used to improve the set of EEG-based image labels before propagating them to the unseen images for the final retrieval. In our approach we accumulate the evidence of the true labels for each image in the database through iterations. This is done by propagating the EEG-based labels of the presented images at each iteration to the rest of images in the database. Our results demonstrate a continuous improvement of the labeling performance across iterations despite the moderate EEG-based labeling (AUC <75%). The overall analysis is done in terms of the single-trial EEG decoding performance and the image database reorganization quality. Furthermore, we discuss the EEG-based labeling performance with respect to a search task given the same image database. 相似文献
68.
A Systematic Review of Risk Factors Associated with Surgical Site Infections among Surgical Patients
Ellen Korol Karissa Johnston Nathalie Waser Frangiscos Sifakis Hasan S. Jafri Mathew Lo Moe H. Kyaw 《PloS one》2013,8(12)
Importance
Surgical site infection (SSI) complicates 2-5% of surgeries in the United States. Severity of SSI ranges from superficial skin infection to life-threatening conditions such as severe sepsis, and SSIs are responsible for increased morbidity, mortality, and economic burden associated with surgery. Staphylococcus aureus (S. aureus) is a commonly-isolated organism for SSI, and methicillin-resistant S. aureus SSI incidence is increasing globally.Objective
The objective of this systematic review was to characterize risk factors for SSI within observational studies describing incidence of SSI in a real-world setting.Evidence Review
An initial search identified 328 titles published in 2002-2012; 57 were identified as relevant for data extraction. Extracted information included study design and methodology, reported cumulative incidence and post-surgical time until onset of SSI, and odds ratios and associated variability for all factors considered in univariate and/or multivariable analyses.Findings
Median SSI incidence was 3.7%, ranging from 0.1% to 50.4%. Incidence of overall SSI and S. aureus SSI were both highest in tumor-related and transplant surgeries. Median time until SSI onset was 17.0 days, with longer time-to-onset for orthopedic and transplant surgeries. Risk factors consistently identified as associated with SSI included co-morbidities, advanced age, risk indices, patient frailty, and surgery complexity. Thirteen studies considered diabetes as a risk factor in multivariable analysis; 85% found a significant association with SSI, with odds ratios ranging from 1.5-24.3. Longer surgeries were associated with increased SSI risk, with a median odds ratio of 2.3 across 11 studies reporting significant results.Conclusions and Relevance
In a broad review of published literature, risk factors for SSI were characterized as describing reduced fitness, patient frailty, surgery duration, and complexity. Recognition of risk factors frequently associated with SSI allows for identification of such patients with the greatest need for optimal preventive measures to be identified and pre-treatment prior to surgery. 相似文献69.
Jo?o Miguel Freire Ana Salomé Veiga Thaís M. Concei??o Wioleta Kowalczyk Ronaldo Mohana-Borges David Andreu Nuno C. Santos Andrea T. Da Poian Miguel A. R. B. Castanho 《PloS one》2013,8(12)
Supercharged proteins are a recently identified class of proteins that have the ability to efficiently deliver functional macromolecules into mammalian cells. They were first developed as bioengineering products, but were later found in the human proteome. In this work, we show that this class of proteins with unusually high net positive charge is frequently found among viral structural proteins, more specifically among capsid proteins. In particular, the capsid proteins of viruses from the Flaviviridae family have all a very high net charge to molecular weight ratio (> +1.07/kDa), thus qualifying as supercharged proteins. This ubiquity raises the hypothesis that supercharged viral capsid proteins may have biological roles that arise from an intrinsic ability to penetrate cells. Dengue virus capsid protein was selected for a detailed experimental analysis. We showed that this protein is able to deliver functional nucleic acids into mammalian cells. The same result was obtained with two isolated domains of this protein, one of them being able to translocate lipid bilayers independently of endocytic routes. Nucleic acids such as siRNA and plasmids were delivered fully functional into cells. The results raise the possibility that the ability to penetrate cells is part of the native biological functions of some viral capsid proteins. 相似文献
70.
Mohd Amir Taj Mohammad Kartikay Prasad Gulam Mustafa Hasan Vijay Kumar Ravins Dohare 《Journal of biomolecular structure & dynamics》2020,38(15):4625-4634
Communicated by Ramaswamy H. Sarma 相似文献