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排序方式: 共有336条查询结果,搜索用时 15 毫秒
61.
Miguel A. Lanaspa Laura G. Sanchez-Lozada Christina Cicerchi Nanxing Li Carlos A. Roncal-Jimenez Takuji Ishimoto Myphuong Le Gabriela E. Garcia Jeffrey B. Thomas Christopher J. Rivard Ana Andres-Hernando Brandi Hunter George Schreiner Bernardo Rodriguez-Iturbe Yuri Y. Sautin Richard J. Johnson 《PloS one》2012,7(10)
62.
ML Zupancic BL Cantarel Z Liu EF Drabek KA Ryan S Cirimotich C Jones R Knight WA Walters D Knights EF Mongodin RB Horenstein BD Mitchell N Steinle S Snitker AR Shuldiner CM Fraser 《PloS one》2012,7(8):e43052
Obesity has been linked to the human gut microbiota; however, the contribution of gut bacterial species to the obese phenotype remains controversial because of conflicting results from studies in different populations. To explore the possible dysbiosis of gut microbiota in obesity and its metabolic complications, we studied men and women over a range of body mass indices from the Old Order Amish sect, a culturally homogeneous Caucasian population of Central European ancestry. We characterized the gut microbiota in 310 subjects by deep pyrosequencing of bar-coded PCR amplicons from the V1-V3 region of the 16S rRNA gene. Three communities of interacting bacteria were identified in the gut microbiota, analogous to previously identified gut enterotypes. Neither BMI nor any metabolic syndrome trait was associated with a particular gut community. Network analysis identified twenty-two bacterial species and four OTUs that were either positively or inversely correlated with metabolic syndrome traits, suggesting that certain members of the gut microbiota may play a role in these metabolic derangements. 相似文献
63.
Rebecca M. DuBois P. Jake Slavish Brandi M. Baughman Mi-Kyung Yun Ju Bao Richard J. Webby Thomas R. Webb Stephen W. White 《PLoS pathogens》2012,8(8)
Emerging influenza viruses are a serious threat to human health because of their pandemic potential. A promising target for the development of novel anti-influenza therapeutics is the PA protein, whose endonuclease activity is essential for viral replication. Translation of viral mRNAs by the host ribosome requires mRNA capping for recognition and binding, and the necessary mRNA caps are cleaved or “snatched” from host pre-mRNAs by the PA endonuclease. The structure-based development of inhibitors that target PA endonuclease is now possible with the recent crystal structure of the PA catalytic domain. In this study, we sought to understand the molecular mechanism of inhibition by several compounds that are known or predicted to block endonuclease-dependent polymerase activity. Using an in vitro endonuclease activity assay, we show that these compounds block the enzymatic activity of the isolated PA endonuclease domain. Using X-ray crystallography, we show how these inhibitors coordinate the two-metal endonuclease active site and engage the active site residues. Two structures also reveal an induced-fit mode of inhibitor binding. The structures allow a molecular understanding of the structure-activity relationship of several known influenza inhibitors and the mechanism of drug resistance by a PA mutation. Taken together, our data reveal new strategies for structure-based design and optimization of PA endonuclease inhibitors. 相似文献
64.
Minxian Dai Brandi Freeman Henry J. Shikani Fernando Pereira Bruno J. Elias Collado Rolando Macias Sandra E. Reznik Peter Davies David Conover Spray Herbert Bernard Tanowitz Louis Martin Weiss Mahalia Sabrina Desruisseaux 《PloS one》2012,7(10)
Neurological and cognitive impairment persist in more than 20% of cerebral malaria (CM) patients long after successful anti-parasitic treatment. We recently reported that long term memory and motor coordination deficits are also present in our experimental cerebral malaria model (ECM). We also documented, in a murine model, a lack of obvious pathology or inflammation after parasite elimination, suggesting that the long-term negative neurological outcomes result from potentially reversible biochemical and physiological changes in brains of ECM mice, subsequent to acute ischemic and inflammatory processes. Here, we demonstrate for the first time that acute ECM results in significantly reduced activation of protein kinase B (PKB or Akt) leading to decreased Akt phosphorylation and inhibition of the glycogen kinase synthase (GSK3β) in the brains of mice infected with Plasmodium berghei ANKA (PbA) compared to uninfected controls and to mice infected with the non-neurotrophic P. berghei NK65 (PbN). Though Akt activation improved to control levels after chloroquine treatment in PbA-infected mice, the addition of lithium chloride, a compound which inhibits GSK3β activity and stimulates Akt activation, induced a modest, but significant activation of Akt in the brains of infected mice when compared to uninfected controls treated with chloroquine with and without lithium. In addition, lithium significantly reversed the long-term spatial and visual memory impairment as well as the motor coordination deficits which persisted after successful anti-parasitic treatment. GSK3β inhibition was significantly increased after chloroquine treatment, both in lithium and non-lithium treated PbA-infected mice. These data indicate that acute ECM is associated with abnormalities in cell survival pathways that result in neuronal damage. Regulation of Akt/GSK3β with lithium reduces neuronal degeneration and may have neuroprotective effects in ECM. Aberrant regulation of Akt/GSK3β signaling likely underlies long-term neurological sequelae observed in ECM and may yield adjunctive therapeutic targets for the management of CM. 相似文献
65.
66.
Spongiform degeneration is characterized by vacuolation in nervous tissue accompanied by neuronal death and gliosis. Although spongiform degeneration is a hallmark of prion diseases, this pathology is also present in the brains of patients suffering from Alzheimer's disease, diffuse Lewy body disease, human immunodeficiency virus (HIV) infection, and Canavan's spongiform leukodystrophy. The shared outcome of spongiform degeneration in these diverse diseases suggests that common cellular mechanisms must underlie the processes of spongiform change and neurodegeneration in the central nervous system. Immunohistochemical analysis of brain tissues reveals increased ubiquitin immunoreactivity in and around areas of spongiform change, suggesting the involvement of ubiquitin-proteasome system dysfunction in the pathogenesis of spongiform neurodegeneration. The link between aberrant ubiquitination and spongiform neurodegeneration has been strengthened by the discovery that a null mutation in the E3 ubiquitin-protein ligase mahogunin ring finger-1 (Mgrn1) causes an autosomal recessively inherited form of spongiform neurodegeneration in animals. Recent studies have begun to suggest that abnormal ubiquitination may alter intracellular signaling and cell functions via proteasome-dependent and proteasome-independent mechanisms, leading to spongiform degeneration and neuronal cell death. Further elucidation of the pathogenic pathways involved in spongiform neurodegeneration should facilitate the development of novel rational therapies for treating prion diseases, HIV infection, and other spongiform degenerative disorders. 相似文献
67.
Maria Luisa Brandi Luigi Gennari Marco Matucci Cerinic Lucia Becherini Alberto Falchetti Laura Masi Carlo Gennari Jean-Yves Reginster 《Arthritis research & therapy》2001,3(5):270-11
Osteoarthritis and osteoporosis are the two most common age-related chronic disorders of articular joints and skeleton, representing
a major public health problem in most developed countries. Apart from being influenced by environmental factors, both disorders
have a strong genetic component, and there is now considerable evidence from large population studies that these two disorders
are inversely related. Thus, an accurate analysis of the genetic component of one of these two multifactorial diseases may
provide data of interest for the other. However, the existence of confounding factors must always be borne in mind in interpreting
the genetic analysis. In addition, each patient must be given an accurate clinical evaluation, including family history, history
of drug treatments, lifestyle, and environment, in order to reduce the background bias. Here, we review the impact of recent
work in molecular genetics suggesting that powerful molecular biology techniques will soon make possible both a rapid accumulation
of data on the genetics of both disorders and the development of novel diagnostic, prognostic, and therapeutic approaches. 相似文献
68.
Piccoli-Valle Roberta Hilsdorf Brandi Igor Viana Silva Daison Olzany Vieira Passos Frederico José 《World journal of microbiology & biotechnology》2001,17(5):433-437
Penicillium griseoroseum cultured in the presence of sucrose and yeast extract produces pectin lyase (EC 4.2.2.10) (PL) in the absence of its natural inducer pectin. This fungus was cultured in a fermenter at an aeration rate of 0.5 l/min for the first 25 h and 1.0 l/min for the remainder of the culture period, and at a stirring rate of 200 rev/min for the entire culture period. Fungal spores were inoculated directly into the fermenter at a final concentration of 5 × 104 spores/ml. The fungus was cultured in minimal medium supplemented with powdered dehydrated sugar cane juice, producing PL without added yeast extract. Maximum PL activity (0.067 IU/ml) was obtained after 65 h in batch culture. Pellet morphology of the mycelia made it possible to carry out three cycles of repeated batch culture. The same medium was used for renewal as for the single batch culture. The initial cycle was 53 h, after which approximately 0.103 IU/ml of PL was obtained. After this period, the medium was renewed and fermentation continued for two more cycles, which lasted approximately 20 h. Activity of PL obtained in the second cycle was approximately 0.118 IU/ml and in the third, approximately 0.109 IU/ml. 相似文献
69.
Bacterial lipoproteins and other factors released by Francisella tularensis modulate human neutrophil lifespan: Effects of a TLR1 SNP on apoptosis inhibition
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Lauren C. Kinkead Laura C. Whitmore Jenna M. McCracken Joshua R. Fletcher Brandi B. Ketelsen Justin W. Kaufman Bradley D. Jones David S. Weiss Jason H. Barker Lee‐Ann H. Allen 《Cellular microbiology》2018,20(2)
Francisella tularensis infects several cell types including neutrophils, and aberrant neutrophil accumulation contributes to tissue destruction during tularaemia. We demonstrated previously that F. tularensis strains Schu S4 and live vaccine strain markedly delay human neutrophil apoptosis and thereby prolong cell lifespan, but the bacterial factors that mediate this aspect of virulence are undefined. Herein, we demonstrate that bacterial conditioned medium (CM) can delay apoptosis in the absence of direct infection. Biochemical analyses show that CM contained F. tularensis surface factors as well as outer membrane components. Our previous studies excluded roles for lipopolysaccharide and capsule in apoptosis inhibition, and current studies of [14C] acetate‐labelled bacteria argue against a role for other bacterial lipids in this process. At the same time, studies of isogenic mutants indicate that TolC and virulence factors whose expression requires FevR or MglA were also dispensable, demonstrating that apoptosis inhibition does not require Type I or Type VI secretion. Instead, we identified bacterial lipoproteins (BLPs) as active factors in CM. Additional studies of isolated BLPs demonstrated dose‐dependent neutrophil apoptosis inhibition via a TLR2‐dependent mechanism that is significantly influenced by a common polymorphism, rs5743618, in human TLR1. These data provide fundamental new insight into pathogen manipulation of neutrophil lifespan and BLP function. 相似文献
70.
Brandi Kiel Reese Laura A. Zinke Morgan S. Sobol Doug E. LaRowe Beth N. Orcutt Xinxu Zhang 《Geomicrobiology journal》2018,35(6):468-483
Microbial ecology within oligotrophic marine sediment is poorly understood, yet is critical for understanding geochemical cycles. Here, 16S rRNA sequences from RNA and DNA inform the structure of active and total microbial communities in oligotrophic sediment on the western flank of the Mid-Atlantic Ridge. Sequences identified as Bacillariophyta chloroplast were detected within DNA, but undetectable within RNA, suggesting preservation in 5.6-million-year-old sediment. Statistical analysis revealed that RNA-based microbial populations correlated significantly with nitrogen concentrations, whereas DNA-based populations did not correspond to measured geochemical analytes. Bioenergetic calculations determined which metabolisms could yield energy in situ, and found that denitrification, nitrification, and nitrogen fixation were all favorable. A metagenome was produced from one sample, and included genes mediating nitrogen redox processes. Nitrogen respiration by active bacteria is an important metabolic strategy in North Pond sediments, and could be widespread in the oligotrophic sedimentary biosphere. 相似文献