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  • Article
    Cui J, Gao N, Wang C, Zhu W, Li J, Wang H, Seidel P, Ravoo BJ, Li G.
    Nanoscale. 2014 Oct 21;6(20):11995-2001.
    Exploiting metal-organic framework (MOF) materials as novel building blocks to construct superstructures with extended and enhanced functions represents a big challenge. In biological systems, the ordering of many components is not achieved by interaction of the components with each other, but by interaction of each component with the host protein which provides a matrix to support the entire assembly. Inspired by biological systems, in this work, a general strategy for efficient spatial arrangement of MOF materials was developed by using spherical colloidal crystals as host matrices, affording a new class of highly tunable MOF composite spheres with a series of distinctive properties. It was found that the synergetic combination of the unique features of both MOF and photonic colloidal crystal imparted these hierarchically structured spheres intrinsic optical properties, specific molecular recognition with self-reporting signalling, derivatization capability, and anisotropy. More importantly, the unique photonic band-gap structure integrated in these composite spheres provides a more convenient means to manipulate the photophysical and photochemical behaviour of the trapped guest molecules in MOF nanocavities.
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  • Article
    Zhang Q, Huang X.
    PeerJ. 2021;9:e11995.
    Astragalus membranaceus is a traditional Chinese medicine and has been used for adjuvant clinical therapy for a variety of cancers. However, the mechanism of its action on endometrial carcinoma is unclear. Based on the Gene Expression Omnibus (GEO) database, the Cancer Genome Atlas (TCGA) database, and the Traditional Chinese Medicine System Pharmacology Database (TCMSP™), the drug and target compounds were initially screened to construct a common network module. Twenty active compounds in Astragalus membranaceus were successfully identified, which hit by 463 potential targets related to endometrial cancer. Eight of the more highly predictive compounds (such as Jaranol, Bifendate, Isorhamnetin, Calycosin, 7-O-methylisomucronulatol, Formononetin, Kaempferol, Quercetin) were involved in DNA integrity checkpoint, cyclin-dependent protein kinase holoenzyme complex, and histone kinase activity. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway confirmed that Astragalus membranaceus might play a role in the treatment of endometrial cancer through p53 signalling pathway, transcriptional misregulation in cancer, and endometrial cancer signalling pathway. Drug-target-pathway networks were constructed using Cytoscape to provide a visual perspective. In addition, we verified that formononetin inhibited the proliferation of endometrial cancer cells through cell viability tests and clone formation tests. And qPCR and western blot found that formononetin exerts anti-cancer effects by promoting the expression of estrogen receptor beta (ERβ) and p53. Based on a systematic network pharmacology approach, our works successfully predict the active ingredients and potential targets of Astragalus membranaceus for application to endometrial cancer and helps to illustrate mechanism of action on a comprehensive level.
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  • Article
    Zhou C, Yang P.
    Opt Express. 2015 May 04;23(9):11995-2003.
    At a wavelength corresponding to negligible electromagnetic absorption by ice, rigorous numerical simulations based on solving Maxwell's equations show a backscattering peak associated with the phase function of randomly oriented hexagonal ice crystals. The backscattering peak, which has important implications to the interpretation of lidar observations, exists in the cases of smooth regular, smooth irregular, and roughened hexagonal ice crystals. The backscattering peak width is inversely proportional to the size parameter. The theoretical prediction of the backscattering peak is consistent with observations.
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  • Article
    Ruan Y, Boyd K, Ji H, Francois A, Ebendorff-Heidepriem H, Munch J, Monro TM.
    Opt Express. 2014 May 19;22(10):11995-2006.
    High index Er-Yb codoped tellurite spheres with diameter of 9 μm and good sphericity were fabricated using a CO(2) laser. Upconversion modulated whispering gallery modes with a quality factor of 45,000 were observed in the sphere dipped in methanol. Refractometric sensing with detection sensitivity of 7.7 nm/RIU was demonstrated using a 9 μm diameter sphere. Such high index spheres have the potential to be used for nanoparticle sensing and mid-IR frequency conversion.
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  • Article
    Yu Y, Li M, Zhao Y, Fan F, Wu W, Gao Y, Bai C.
    Heliyon. 2022 Dec;8(12):e11995.
    Background: Type 1 diabetes mellitus (T1DM) is an autoimmune disease caused by an autoimmune response against pancreatic islet β cells. Increasing evidence indicates that specific microRNAs (miRNAs) from immune cells extracellular vesicles are involved in islet β cells apoptosis.
    Methods: In this study, the microarray datasets GSE27997 and GSE137637 were downloaded from the Gene Expression Omnibus (GEO) database. miRNAs that promote islet β cells apoptosis in T1DM were searched in PubMed. We used the FunRich tool to determine the miRNA expression in extracellular vesicles derived from immune cells associated with islet β cell apoptosis, of which we selected candidate miRNAs based on fold change expression. Potential upstream transcription factors and downstream target genes of candidate miRNAs were predicted using TransmiR V2.0 and starBase database, respectively.
    Results: Candidate miRNAs expressed in extracellular vesicles derived from T cells, pro-inflammatory macrophages, B cells, and dendritic cells were analyzed to identify the miRNAs involved in β cells apoptosis. Based on these candidate miRNAs, 25 downstream candidate genes, which positively regulate β cell functions, were predicted and screened; 17 transcription factors that positively regulate the candidate miRNAs were also identified.
    Conclusions: Our study demonstrated that immune cell-derived extracellular vesicular miRNAs could promote islet β cell dysfunction and apoptosis. Based on these findings, we have constructed a transcription factor-miRNA-gene regulatory network, which provides a theoretical basis for clinical management of T1DM. This study provides novel insights into the mechanism underlying immune cell-derived extracellular vesicle-mediated islet β cell apoptosis.
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  • Article
    Qi J, Hu KS, Yang HL.
    Int J Clin Exp Pathol. 2015;8(10):11995-2004.
    OBJECTIVE: To investigate the roles of TNF-α, GSK-3β and RANKL in the occurrence and development of diabetic osteoporosis.
    METHODS: Diabetic rat model was established; tissue section technology was used to observe the situation of osteoporosis in diabetic rats; rat serum levels of OC, RANKL, GSK-3β, P38mapk, TNF-α and INS were detected by Elisa assay; osteoblasts and osteoclasts were primarily cultured and identified by immunohistochemistry and tartrate-resistant acid phosphatase (TRAP) staining respectively. The effects of GSK-3β inhibitors, lithium chloride, TNF-α antagonists and RANKL antagonists on the proliferation of osteoblasts and osteoclasts were evaluated; quantitative PCR was used to assess the effects of GSK-3β inhibitors, lithium chloride, on TNF-α and RANKL gene expression in osteoblasts and osteoclasts, and the effects of TNF-α and RANKL antagonists on GSK-3β gene expression in osteoblasts and osteoclasts.
    RESULTS: Diabetic rat model was successfully established; osteoblasts and osteoclasts were successfully isolated and cultured. Elisa experiments showed that in diabetic model group, the levels of RANKL, GSK-3β, P38mapk and TNF-α were significantly increased, while the levels of osteocalcin (OC) and insulin (INS) were significantly reduced; MTT results showed that osteoclast proliferation in GSK-3β inhibitor and lithium chloride groups were weaker than the untreated group, while osteoclast proliferation in TNF-α antagonist group and RANKL antagonist Group was very close to the untreated group. Osteoblast proliferation in GSK-3β inhibitor and lithium chloride groups were weaker than the untreated group, while osteoblast proliferation in TNF-α antagonist group and RANKL antagonist group was higher than the untreated group. In all of the corresponding groups, cell proliferation in the diabetic group was stronger than the untreated group. In GSK-3β inhibitor and lithium oxide groups, TNF-α and RANKL gene expression levels were elevated, but TNF-α and RANKL gene expression levels in the diabetic group were slightly lower than the control group. GSK-3β gene expression level in TNF-α antagonist group and RANKL antagonist group was reduced; GSK-3β gene expression level in diabetic group was lower than the control group.
    CONCLUSION: In diabetic rats, TNF-α, GSK-3β and RANKL levels were elevated; GSK-3β could promote the proliferation of osteoblasts and osteoclasts, and inhibit the expression of TNF-α and RANKL; TNF-α and RANKL can suppress the proliferation of osteoblasts while had little effect on osteoclast proliferation; they also can promote the GSK-3β gene expression; interactions between the three broke the balance between osteoblasts and osteoclasts, leading to osteoporosis.
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  • Article
    Aridgides DS, Mellinger DL, Gwilt LL, Hampton TH, Mould DL, Hogan DA, Ashare A.
    Sci Rep. 2023 07 25;13(1):11995.
    Macrophage dysfunction has been well-described in Cystic Fibrosis (CF) and may contribute to bacterial persistence in the lung. Whether CF macrophage dysfunction is related directly to Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in macrophages or an indirect consequence of chronic inflammation and mucostasis is a subject of ongoing debate. CFTR modulators that restore CFTR function in epithelial cells improve global CF monocyte inflammatory responses but their direct effects on macrophages are less well understood. To address this knowledge gap, we measured phagocytosis, metabolism, and cytokine expression in response to a classical CF pathogen, Pseudomonas aeruginosa in monocyte-derived macrophages (MDM) isolated from CF F508del homozygous subjects and nonCF controls. Unexpectedly, we found that CFTR modulators enhanced phagocytosis in both CF and nonCF cohorts. CFTR triple modulators also inhibited MDM mitochondrial function, consistent with MDM activation. In contrast to studies in humans where CFTR modulators decreased serum inflammatory cytokine levels, modulators did not alter cytokine secretion in our system. Our studies therefore suggest modulator induced metabolic effects may promote bacterial clearance in both CF and nonCF monocyte-derived macrophages.
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  • Article
    Wolf AI, Strauman MC, Mozdzanowska K, Whittle JR, Williams KL, Sharpe AH, Weiser JN, Caton AJ, Hensley SE, Erikson J.
    J Virol. 2014 Oct;88(20):11995-2005.
    Pathogen-specific antibodies (Abs) protect against respiratory infection with influenza A virus (IAV) and Streptococcus pneumoniae and are the basis of effective vaccines. Sequential or overlapping coinfections with both pathogens are common, yet the impact of coinfection on the generation and maintenance of Ab responses is largely unknown. We report here that the B cell response to IAV is altered in mice coinfected with IAV and S. pneumoniae and that this response differs, depending on the order of pathogen exposure. In mice exposed to S. pneumoniae prior to IAV, the initial virus-specific germinal center (GC) B cell response is significantly enhanced in the lung-draining mediastinal lymph node and spleen, and there is an increase in CD4(+) T follicular helper (TFH) cell numbers. In contrast, secondary S. pneumoniae infection exaggerates early antiviral antibody-secreting cell formation, and at later times, levels of GCs, TFH cells, and antiviral serum IgG are elevated. Mice exposed to S. pneumoniae prior to IAV do not maintain the initially robust GC response in secondary lymphoid organs and exhibit reduced antiviral serum IgG with diminished virus neutralization activity a month after infection. Our data suggest that the history of pathogen exposures can critically affect the generation of protective antiviral Abs and may partially explain the differential susceptibility to and disease outcomes from IAV infection in humans. Importance: Respiratory tract coinfections, specifically those involving influenza A viruses and Streptococcus pneumoniae, remain a top global health burden. We sought to determine how S. pneumoniae coinfection modulates the B cell immune response to influenza virus since antibodies are key mediators of protection.
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  • Article
    Yu X, Jembere F, Takehara-Nishiuchi K.
    Sci Rep. 2022 07 14;12(1):11995.
    The nucleus reuniens (RE) is necessary for memories dependent on the interaction between the medial prefrontal cortex (mPFC) and hippocampus (HPC). One example is trace eyeblink conditioning, in which the mPFC exhibits differential activity to neutral conditioned stimuli (CS) depending on their contingency with an aversive unconditioned stimulus (US). To test if this relevancy signal is routed to the RE, we photometrically recorded mPFC axon terminals within the RE and tracked their changes with learning. As a comparison, we measured prefrontal terminal activity in the mediodorsal thalamus (MD), which lacks connectivity with the HPC. In naïve male rats, prefrontal terminals within the RE were not strongly activated by tone or light. As the rats associated one of the stimuli (CS+) with the US, terminals gradually increased their response to the CS+ but not the other stimulus (CS-). In contrast, stimulus-evoked responses of prefrontal terminals within the MD were strong even before conditioning. They also became augmented only to the CS+ in the first conditioning session; however, the degree of activity differentiation did not improve with learning. These findings suggest that associative learning selectively increased mPFC output to the RE, signaling the behavioral relevance of sensory stimuli.
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  • Article
    Nakajima H, Kobayashi I, Adachi Y, Hisatomi O.
    Sci Rep. 2021 06 07;11(1):11995.
    Light-Oxygen-Voltage (LOV) domains are responsible for detecting blue light (BL) and regulating the activities of effector domains in various organisms. Photozipper (PZ), an N-terminally truncated aureochrome-1 protein, contains a LOV domain and a basic leucin zipper (bZIP) domain and plays a role as a light-activatable transcription factor. PZ is monomeric in the dark state and undergoes non-covalent dimerization upon illumination with BL, subsequently increasing its affinity for the target DNA. To clarify the molecular mechanism of aureochromes, we prepared site-directed mutants of PZ and performed quantitative analyses in the dark and light states. Although the amino acid substitutions in the hinge region between the LOV core and A'α helix had minor effects on the dimerization and DNA-binding properties of PZ, the substitutions in the β-sheet region of the LOV core and in the A'α helix significantly affected these properties. We found that light signals are transmitted from the LOV core to the effector bZIP domain via the hydrophobic residues on the β-sheet. The light-induced conformational change possibly deforms the hydrophobic regions of the LOV core and induces the detachment of the A'α helix to expose the dimerization surface, likely activating the bZIP domain in a light-dependent manner.
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  • Article
    Bubendorfer S, Krebes J, Yang I, Hage E, Schulz TF, Bahlawane C, Didelot X, Suerbaum S.
    Nat Commun. 2016 06 22;7:11995.
    Recombination plays a dominant role in the evolution of the bacterial pathogen Helicobacter pylori, but its dynamics remain incompletely understood. Here we use an in vitro transformation system combined with genome sequencing to study chromosomal integration patterns after natural transformation. A single transformation cycle results in up to 21 imports, and repeated transformations generate a maximum of 92 imports (8% sequence replacement). Import lengths show a bimodal distribution with averages of 28 and 1,645 bp. Reanalysis of paired H. pylori genomes from chronically infected people demonstrates the same bimodal import pattern in vivo. Restriction endonucleases (REases) of the recipient bacteria fail to inhibit integration of homeologous DNA, independently of methylation. In contrast, REases limit the import of heterologous DNA. We conclude that restriction-modification systems inhibit the genomic integration of novel sequences, while they pose no barrier to homeologous recombination, which reconciles the observed stability of the H. pylori gene content and its highly recombinational population structure.
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  • Article
    Ortiz JF, Ghani MR, Morillo Cox Á, Tambo W, Bashir F, Wirth M, Moya G.
    Cureus. 2020 Dec 09;12(12):e11995.
    Stiff-person syndrome (SPS) is a rare and disabling central nervous system disorder with no satisfactory treatment. Muscle rigidity, sporadic muscle spasms, and chronic muscle pain characterize SPS. SPS is strongly correlated with autoimmune diseases, and it is usual to find high titers of antibodies against acid decarboxylase (GAD65). Due to its highly disabling nature and complicated treatment, we aim to create a treatment protocol through a narrative review of currently available treatments that show efficacy. We expect to facilitate management based on treatment responses ranging from first-line medication to refractory medication. We conducted a medical subject heading (MeSH) strategy. We used the term SPS with the subheading treatment: "Stiff-Person Syndrome/Therapy" [MeSH]. An initial data gathering of 270 papers came out with the initial research. After using the inclusion criteria, we had 159 articles. We excluded 31 papers for being either systematic reviews, literature reviews, or meta-analysis. From the 128 remaining articles, we excluded another 104 papers because the extraction of the data was not possible or the study outcome did not meet our demands. There are two main treatments for SPS: GABAergic (gamma-aminobutyric acid) therapy and immunotherapy. For treatment, we suggest starting with benzodiazepines as first-line treatment. We recommend adding levetiracetam or pregabalin if symptoms persist. As second-line therapy, we recommend oral baclofen over rituximab and tacrolimus. We also suggest rituximab over tacrolimus. For patients with refractory treatment, we can use intrathecal baclofen, intravenous immunoglobulin (IVIG), or plasmapheresis. We conclude that intrathecal baclofen and IVIG are more effective than plasmapheresis in patients with refractory symptoms. Propofol may be used as a bridge - temporary therapy before initiating a permanent treatment.
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  • Article
    Halsør MH, Altermark B, Ræder ILU.
    Sci Rep. 2020 07 20;10(1):11995.
    Nonulosonic acid (NulO) biosynthesis in bacteria is directed by nab gene clusters that can lead to neuraminic, legionaminic or pseudaminic acids. Analysis of the gene content from a set mainly composed of Aliivibrio salmonicida and Moritella viscosa strains reveals the existence of several unique nab clusters, for which the NulO products were predicted. This prediction method can be used to guide tandem mass spectrometry studies in order to verify the products of previously undescribed nab clusters and identify new members of the NulOs family.
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  • Article
    Bodewes R, Fraaij PL, Geelhoed-Mieras MM, van Baalen CA, Tiddens HA, van Rossum AM, van der Klis FR, Fouchier RA, Osterhaus AD, Rimmelzwaan GF.
    J Virol. 2011 Nov;85(22):11995-2000.
    Infection with seasonal influenza A viruses induces immunity to potentially pandemic influenza A viruses of other subtypes (heterosubtypic immunity). We recently demonstrated that vaccination against seasonal influenza prevented the induction of heterosubtypic immunity against influenza A/H5N1 virus induced by infection with seasonal influenza in animal models, which correlated with the absence of virus-specific CD8(+) T cell responses. Annual vaccination of all healthy children against influenza has been recommended, but the impact of vaccination on the development of the virus-specific CD8(+) T cell immunity in children is currently unknown. Here we compared the virus-specific CD8(+) T cell immunity in children vaccinated annually with that in unvaccinated children. In the present study, we compared influenza A virus-specific cellular and humoral responses of unvaccinated healthy control children with those of children with cystic fibrosis (CF) who were vaccinated annually. Similar virus-specific CD4(+) T cell and antibody responses were observed, while an age-dependent increase of the virus-specific CD8(+) T cell response that was absent in vaccinated CF children was observed in unvaccinated healthy control children. Our results indicate that annual influenza vaccination is effective against seasonal influenza but hampers the development of virus-specific CD8(+) T cell responses. The consequences of these findings are discussed in the light of the development of protective immunity to seasonal and future pandemic influenza viruses.
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  • Article
    Danyel M, Ott CE, Grenkowitz T, Salewsky B, Hicks AA, Fuchsberger C, Steinhagen-Thiessen E, Bobbert T, Kassner U, Demuth I.
    Sci Rep. 2019 08 19;9(1):11995.
    Familial hypercholesterolemia (FH) is characterised by elevated serum levels of low-density lipoprotein cholesterol (LDL-C) and a substantial risk for cardiovascular disease. The autosomal-dominant FH is mostly caused by mutations in LDLR (low density lipoprotein receptor), APOB (apolipoprotein B), and PCSK9 (proprotein convertase subtilisin/kexin). Recently, STAP1 has been suggested as a fourth causative gene. We analyzed STAP1 in 75 hypercholesterolemic patients from Berlin, Germany, who are negative for mutations in canonical FH genes. In 10 patients with negative family history, we additionally screened for disease causing variants in LDLRAP1 (low density lipoprotein receptor adaptor protein 1), associated with autosomal-recessive hypercholesterolemia. We identified one STAP1 variant predicted to be disease causing. To evaluate association of serum lipid levels and STAP1 carrier status, we analyzed 20 individuals from a population based cohort, the Cooperative Health Research in South Tyrol (CHRIS) study, carrying rare STAP1 variants. Out of the same cohort we randomly selected 100 non-carriers as control. In the Berlin FH cohort STAP1 variants were rare. In the CHRIS cohort, we obtained no statistically significant differences between carriers and non-carriers of STAP1 variants with respect to lipid traits. Until such an association has been verified in more individuals with genetic variants in STAP1, we cannot estimate whether STAP1 generally is a causative gene for FH.
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  • Article
    Panda BR, Singh AK, Ramesh A, Chattopadhyay A.
    Langmuir. 2008 Oct 21;24(20):11995-2000.
    Herein we present a facile method for rapid quantitation of bacterial cells over several logarithmic dilutions. The quantitation is based on loss of the fluorescence intensity of a positively charged Au nanoparticle-polythiophene composite in the presence of bacterial cells. The present method allowed estimation of both Gram-positive and Gram-negative bacteria with cells as low as 1000. Transmission electron microscopic investigations revealed attachment of the composite with bacteria with no discernible change in the morphology of the cells. Further, dynamic light scattering experiments indicated preferential attachment of smaller composite particles over larger ones, which were also attached at higher bacterial concentrations. The ease of operation with minimal sample manipulation steps, high sensitivity, quantitative detection, and its generality offer specific advantages over conventional methods.
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  • Article
    Lee S, Koo H, Kwon O, Jae Park Y, Choi H, Lee K, Ahn B, Min Park Y.
    Sci Rep. 2017 09 20;7(1):11995.
    The design of novel exciplex-forming co-host materials provides new opportunities to achieve high device performance of organic light emitting diodes (OLEDs), including high efficiency, low driving voltage and low efficiency roll-off. Here, we report a comprehensive study of exciplex-forming co-host system in OLEDs including the change of co-host materials, mixing composition of exciplex in the device to improve the performance. We investigate various exciplex systems using 5-(3-4,6-diphenyl-1,3,5-triazin-2-yl)phenyl-3,9-diphenyl-9H-carbazole, 5-(3-4,6-diphenyl-1,3,5-triazin-2-yl)phenyl)-9-phenyl-9H-3,9'-bicarbazole, and 2-(3-(6,9-diphenyl-9H-carbazol-4-yl)phenyl)-4-phenylbenzo[4,5]thieno[3,2-d]pyrimidine, as electron transporting (ET: electron acceptor) hosts and 9,9'-dipenyl-9H, 9'H-3,3'-bicarbazole and 9-([1,1'-biphenyl]-4-yl)-9'-phenyl-9H,9'H-3,3'-bicarbazole as hole transporting (HT: electron donor) hosts. As a result, a very high current efficiency of 105.1 cd/A at 103 cd/m2 and an extremely long device lifetime of 739 hrs (t95: time after 5% decrease of luminance) are achieved which is one of the best performance in OLEDs. Systematic approach, controlling mixing ratio of HT to ET host materials is suggested to select the component of two host system using energy band matching and charge balance optimization method. Furthermore, our analysis on exciton stability also reveal that lifetime of OLEDs have close relationship with two parameters; singlet energy level difference of HT and ET host and difference of singlet and triplet energy level in exciplex.
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  • Article
    Kurt H, Citrin DS.
    Opt Express. 2008 Aug 04;16(16):11995-2001.
    We present the design and analysis of a novel reconfigurable photonic-crystal waveguide (PCW). The predefined waveguide is the result of the refractive-index variation of three rows of holes that can be obtained by the infiltration of liquids within what are otherwise air holes in a two-dimensional triangular-lattice photonic crystal. We compute the power transmission through the reconfigurable PCWs as well as through arbitrary waveguide bends. The advantages of writing reconfigurable PCW of a multimode nature are highlighted. We demonstrate the necessity to infiltrate high-refractive-index substances to obtain efficient power transfer via reconfigurable manner.
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  • Article
    Karim ZA, Choi W, Whiteheart SW.
    J Biol Chem. 2008 May 02;283(18):11995-2003.
    Previous studies showed that ADP-ribosylation factor 6 (Arf6) is important for platelet function; however, little is known about which signaling events regulate this small GTP-binding protein. Arf6-GTP was monitored in platelets stimulated with a number of agonists (TRAP, thrombin, convulxin, collagen, PMA, thapsigargin, or A23187) and all led to a time-dependent decrease in Arf6-GTP. ADP and U46619 were without effect. Using inhibitors, it was shown that the decrease of Arf6-GTP is a direct consequence of known signaling cascades. Upon stimulation via PAR receptors, Arf6-GTP loss could be blocked by treatment with U-73122, BAPTA/AM, Ro-31-8220, or Gö6976, indicating requirements for phospholipase C, calcium, and protein kinase C (PKC) alpha/beta, respectively. The Arf6-GTP decrease in convulxin-stimulated platelets showed similar requirements and was also sensitive to piceatannol, wortmannin, and LY294002, indicating additional requirements for Syk and phosphatidylinositol 3-kinase. The convulxin-induced decrease was sensitive to both PKCalpha/beta and delta inhibitors. Outside-in signaling, potentially via integrin engagement, caused a second wave of signaling that affected Arf6. Inclusion of RGDS peptides or EGTA, during activation, led to a biphasic response; Arf6-GTP levels partially recovered upon continued incubation. A similar response was seen in beta3 integrin-null platelets. These data show that Arf6-GTP decreases in response to known signaling pathways associated with PAR and GPVI. They further reveal a second, aggregation-dependent, process that dampens Arf6-GTP recovery. This study demonstrates that the nucleotide state of Arf6 in platelets is regulated during the initial phases of activation and during the later stages of aggregation.
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  • Article
    Lee YK, Lee M.
    Medicine (Baltimore). 2018 Aug;97(35):e11995.
    INTRODUCTION: Infected segmental loss of the Achilles tendon with overlying soft tissue and skin defect remains a more complex reconstructive challenge. Here, we present a functional reconstruction of infected Achilles tendinitis with combined soft tissue defects using a free composite anterolateral thigh (ALT) flap with vascularized fascia lata in an elderly patient.
    CASE PRESENTATION: A 71-year-old male patient was transferred to our department due to soft tissue defect of the left lower leg and infected Achilles tendinitis. The patient underwent incision and drainage of both lower legs with necrotizing fasciitis in another hospital 2 months ago. Physical examination revealed a 12 × 5 cm wound with exposed Achilles tendon over the posteromedial aspect of lower one-third of the leg. His wound culture grew methicillin-resistant Staphylococcus aureus (MRSA). All infected necrotic Achilles tendon with proximal muscle tissue was excised. The patient underwent successful Achilles tendon reconstruction and soft tissue coverage procedure with a 14 × 7 cm ALT flap with the fascia lata. At the 12-month follow-up, the patient resumed full daily activities, was able to squat, showed a range of motion at the ankle in the 15° dorsiflexion and 45° plantar flexion, and the American Orthopaedic Foot and Ankle Society (AOFAS) score was 94.
    CONCLUSION: A free ALT composite flap with the vascularized fascia lata, was successfully used for the treatment of infected Achilles tendinitis with overlying soft tissue defect even in an elderly patient. Furthermore, it provided satisfactory functional and cosmetic outcomes. Hence, the use of free ALT composite flap is highly recommended in such patients.
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