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61.
Antibiotic therapy for inpatients with community‐acquired pneumonia in a developing country 下载免费PDF全文
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Jin Yong Lee Sang Jun Eun Minsu Ock Hyun Joo Kim Hyeon-Jeong Lee Woo-Seung Son Min-Woo Jo 《Journal of Korean medical science》2015,30(5):523-532
Although primary care has been recognized as an essential element of the healthcare system, the primary healthcare of Korea has not been highly valued. Listening to the voices of physicians who are engaged in primary care should be the first step for improving the level of primary care in Korea. In this study, we conducted a questionnaire survey of general internists to investigate their perspectives regarding primary care, and which included the evaluation of current primary care, perception of the five, key attributes of primary care, and their opinions regarding the management system of chronic diseases. A total of 466 general internists'' responses were used in this analysis. The results showed that primary care is considered to have an important role, according to general internists, although their evaluation of the overall status of primary care in Korea indicated that it is poor. The respondents also indicated that the functions of coordination and comprehensiveness in primary care, which can be integral for treating patients with chronic diseases, are most vulnerable. Given the high level of agreement regarding the need for a new medical management system for chronic diseases, based on physicians'' autonomy and provided by clinics, establishing a policy encouraging the participation of general internists should be emphasized.
Graphical Abstract
相似文献64.
A selective role of calcineurin aalpha in synaptic depotentiation in hippocampus 总被引:1,自引:0,他引:1 下载免费PDF全文
Zhuo M Zhang W Son H Mansuy I Sobel RA Seidman J Kandel ER 《Proceedings of the National Academy of Sciences of the United States of America》1999,96(8):4650-4655
Pharmacological studies have suggested that long-term potentiation (LTP) and long-term depression (LTD) and depotentiation, three forms of synaptic plasticity in the hippocampus, require the activity of the phosphatase calcineurin. At least two different isoforms of calcineurin are found in the central nervous system. To investigate whether all of these forms of synaptic plasticity require the same isoforms of calcineurin, we have examined LTD, depotentiation, and LTP in mice lacking the predominant calcineurin isoform in the central nervous system, Aalpha-/- mice. Depotentiation was abolished completely whereas neither LTD nor LTP were affected. These studies provide genetic evidence that the Aalpha isoform of calcineurin is important for the reversal of LTP in the hippocampus and indicate that depotentiation and LTD operate through somewhat different molecular mechanisms. 相似文献
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Ka Man Carmen Chan Ashley L. Arthur Johannes Morstein Meiyan Jin Abrar Bhat Drte Schlesinger Sungmin Son Dont A. Stevens David G. Drubin Daniel A. Fletcher 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(1)
Fusion-associated small transmembrane (FAST) proteins are a diverse family of nonstructural viral proteins. Once expressed on the plasma membrane of infected cells, they drive fusion with neighboring cells, increasing viral spread and pathogenicity. Unlike viral fusogens with tall ectodomains that pull two membranes together through conformational changes, FAST proteins have short fusogenic ectodomains that cannot bridge the intermembrane gap between neighboring cells. One orthoreovirus FAST protein, p14, has been shown to hijack the actin cytoskeleton to drive cell-cell fusion, but the actin adaptor-binding motif identified in p14 is not found in any other FAST protein. Here, we report that an evolutionarily divergent FAST protein, p22 from aquareovirus, also hijacks the actin cytoskeleton but does so through different adaptor proteins, Intersectin-1 and Cdc42, that trigger N-WASP–mediated branched actin assembly. We show that despite using different pathways, the cytoplasmic tail of p22 can replace that of p14 to create a potent chimeric fusogen, suggesting they are modular and play similar functional roles. When we directly couple p22 with the parallel filament nucleator formin instead of the branched actin nucleation promoting factor N-WASP, its ability to drive fusion is maintained, suggesting that localized mechanical pressure on the plasma membrane coupled to a membrane-disruptive ectodomain is sufficient to drive cell-cell fusion. This work points to a common biophysical strategy used by FAST proteins to push rather than pull membranes together to drive fusion, one that may be harnessed by other short fusogens responsible for physiological cell-cell fusion.Aquareovirus and orthoreovirus are two genera of the Reoviridae family of segmented double-stranded RNA viruses that form multinucleated syncytia after infection, which can increase viral spread and pathogenicity (1–4). To drive cell-cell fusion, both aquareovirus and orthoreovirus express a nonstructural, fusion-associated small transmembrane (FAST) protein on the plasma membrane of infected cells. The FAST protein is not required for viral entry, and expression of FAST protein alone is sufficient to cause cells to fuse with naïve neighboring cells, forming large multinucleated syncytium (1, 2, 5–12), confirming they are bona fide cell-cell fusogens. Although they have similar function and topology in the membrane, FAST proteins from aquareovirus and orthoreovirus share minimal sequence identity (13). Based on phylogenetic analysis, they are hypothesized to have evolved from a common, likely nonfusogenic, ancestor 510 million years ago (4, 13, 14). Separate gain-of-function events are believed to have produced fusogenic proteins in both aquareovirus and orthoreovirus, with further divergence or acquisition events resulting in the diversity of FAST proteins found in reoviruses today (13).Aquareovirus and orthoreovirus FAST proteins are single-pass membrane proteins of fewer than 200 residues comprised of a mostly disordered cytoplasmic tail, a transmembrane domain, and a small ectodomain of fewer than 40 residues (1, 2). The membrane-disruptive ectodomains of FAST proteins typically have solvent-exposed hydrophobic residues and/or myristoylation motifs that are necessary for cell-cell fusion (5, 15–17). In contrast to other cell-cell fusogens that fuse membranes by pulling them together using conformational changes in their ∼10 nm-tall ectodomains, the ectodomains of FAST proteins have minimal predicted secondary structure, are unlikely to undergo conformational changes to drive membrane fusion (1, 2), and extend only ∼1 nm above the bilayer (5, 18). How such short fusogens can overcome the ∼2 nm repulsive hydration barrier and larger barrier presented by cell surface proteins to reach and fuse with an opposing membrane (5, 18) has been a long-standing question for FAST proteins and other short cell-cell fusogens, such as myomixer and myomaker that are involved in myoblast fusion (19–22).Recently, we found that the FAST protein from reptilian orthoreovirus, p14, hijacks the host cell actin cytoskeleton to drive cell-cell fusion by forming localized branched actin networks (23). This is accomplished through a c-src phosphorylated tyrosine motif, YVNI, in p14’s disordered cytoplasmic tail that binds to a host adaptor protein, Grb2, which then binds to N-WASP and nucleates branched actin assembly. We hypothesize that this directly couples local actin-generated forces to push p14’s short, fusogenic ectodomain into the opposing cell’s plasma membrane (23). While all FAST family proteins have similarly short ectodomains, it is unclear if this is a general strategy used by other FAST proteins to drive cell-cell fusion.Here, we report that a FAST protein from the divergent aquareovirus, p22, also hijacks the host actin cytoskeleton but does so using a molecular strategy distinct from that of the orthoreovirus FAST protein p14. Instead of binding to Grb2, we find that p22 binds to Intersectin-1 through an SH3 binding motif in its cytoplasmic tail, which binds Cdc42 to activate N-WASP–mediated branched actin assembly. We show that despite minimal sequence identity, the p22 cytoplasmic tail can be functionally swapped with that of p14, suggesting that while the cytoplasmic tails of the two FAST proteins evolved independently, they serve a similar function. By directly coupling the ectodomain to a different actin nucleator, we suggest that actin’s functional role is applying mechanical pressure to a fusogenic ectodomain at the plasma membrane. This biophysical role may be shared across other members of the FAST protein family and could be more generally employed by other cell-cell fusogens. 相似文献
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Lumbar epidural varices are a rare cause of radicular pain mimicking lumbar disc herniation or other cyst-like masses including sequestrated disc herniation, facet joint synovial cyst, or perineural cyst. We report a case of a 36-year-old woman presenting with lumbar radicular pain caused by a lumbar epidural varix. Lumbar magnetic resonance imaging (MRI) revealed a cystic lesion in the ventral epidural space posterior to the right L4 body. Surgery was conducted and histopathology confirmed the diagnosis of an epidural varix. Lumbar epidural varices and other lumbar cystic lesions can commonly cause radicular pain. Physicians will benefit from increased awareness of epidural varices as a cause of lumbosacral radicular pain and the associated radiologic findings supporting differential diagnosis. In particular, careful interpretation of MRI scans may help ensure proper diagnosis of an epidural varix versus other cystic lesions.
Level of Evidence
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Effect of Phosphate Addition on Cadmium Precipitation and Adsorption in Contaminated Arable Soil with a Low Concentration of Cadmium 总被引:1,自引:0,他引:1
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