19 research outputs found
Blood disorders typically associated with renal transplantation
No full textRenal transplantation has become one of the most common surgical procedures performed to replace a diseased kidney with a healthy kidney from a donor. It can help patients with kidney failure live decades longer. However, renal transplantation also faces a risk of developing various blood disorders. The blood disorders typically associated with renal transplantation can be divided into two main categories: 1) Common disorders including post-transplant anemia (PTA), post-transplant lymphoproliferative disorder (PTLD), post-transplant erythrocytosis (PTE) and post-transplant cytopenias (PTC, leukopenia/neutropenia, thrombocytopenia and pancytopenia); and 2) Uncommon but serious disorders including hemophagocytic syndrome (HPS), thrombotic microangiopathy (TMA), therapy-related myelodysplasia (t-MDS), and therapy-related acute myeloid leukemia (t-AML). Although many etiological factors involve the development of post-transplant blood disorders, immunosuppressive agents and viral infections could be the two major contributors to most blood disorders and cause hematological abnormalities and immunodeficiency by suppressing hematopoietic function of bone marrow. Hematological abnormalities and immunodeficiency will result in severe clinical outcomes in renal transplant recipients. Understanding how blood disorders develop will help cure these life-threatening complications. A potential therapeutic strategy against post-transplant blood disorders should focus on tapering immunosuppression or replacing myelotoxic immunosuppressive drugs with lower toxic alternatives, recognizing and treating promptly the etiological virus, bacteria or protozoan, restoring both hematopoietic function of bone marrow and normal blood counts, and improving kidney graft survival
Stigmatic bodies: The corporeal Qiu Miaojin
No full textB1 - Research Book ChaptersDeposited with permission of University of Hawaii PressQiu Miaojin (1969–1995) is Taiwan’s best-known lesbian author. In local lesbian (nütongzhi) subcultures, Qiu’s books are frequently cited as classics, particularly her 1994 novel The Crocodile’s Journal (Eyu shouji), the first novel in Taiwan’s modern literary history to be written by an author commonly known to be a lesbian that takes erotic relationships between women as its central theme. Qiu’s fiction is much celebrated, too, in the mainstream literary establishment; The Crocodile’s Journal won the prestigious China Times Honorary Prize for Literature for Qiu posthumously, following her suicide in mid-1995. Qiu’s unique literary style—mingling cerebral, experimental language use, psychological realism, biting social critique through allegory, and a surrealist effect deriving from the use of arrestingly unusual metaphors—is strongly influenced by both European and Japanese literary and cinematic modernisms. Although her fiction has been compared, in its principal subject-matter, to Radclyffe Hall’s 1920s classic of lesbian alienation, The Well of Loneliness, most frequently cited in Qiu’s writings are male modernist and postmodernist ‘masters’ (many of whose work shows a strongly homoerotic aesthetic) including Andre Gide, Jean Genet, Kobo Abe, Yukio Mishima, Haruki Murakami, Andrei Tarkovsky, and Derek Jarman—locally, Qiu’s work has been critiqued for this apparent masculinist bias. Qiu’s early short stories ‘Zero Degree’ (‘Linjiedian,’ 1988) and ‘Platonic Hair’ (‘Bolatu zhi fa,’ 1990), to be discussed in this chapter, appeared in her first collection, The Revelry of Ghosts (Guide kuanghuan) in 1991, following their earlier serialization in local daily newspapers. They are Qiu’s first works to treat thematically homoerotic desire between women
Pig islets xenotransplantation: recent progress and current perspectives
No full textIslet xenotransplantation is a prospective treatment to bridge the gap between available human cells and needs of patients with diabetes. Pig is the ideal candidate to obtain such available islet cells. However, potential clinical application of pig islet transplantation still faces obstacles such as inadequate yield of high-quality functional islets and xenorejection of the transplants. Adequate amounts of available islets can be obtained based on selection of a suitable pathogen-free source herd and the development of isolation and purification methods. Several studies demonstrated feasibility of successful pre-clinical pig islet xenotransplantation and provided insights and possible mechanisms of xenogeneic immune recognition and rejection. Particularly promising is the achievement of long-term insulin independence in diabetic models by means of distinct islet products and novel immunotherapeutic strategies. Nonetheless, further efforts are needed to obtain much more data on safety and efficacy to translate these findings into clinical practic
Modulation of chloride channel functions by the plant lignan compounds kobusin and eudesmin
No full textPlant lignans are diphenolic compounds widely present in vegetables, fruits and grains. These compounds have been demonstrated to have protective effect against cancer, hypertension and diabetes. In the present study, we showed that two lignan compounds, kobusin and eudesmin, isolated from Magnoliae Flos, could modulate intestinal chloride transport mediated by cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated chloride channels (CaCCs) chloride channels. The compounds potentiated CFTR channel function in both FRT cells and in HT-29 cells. The modulating effects of kobusin and eudesmin on the activity of CaCCgie (CaCC expressed in gastrointestinal epithelial cells) were also investigated, and the result showed that both compounds could stimulate CaCCgie-mediated short-circuit currents and the stimulation was synergistic with ATP. In ex vivo studies, both compounds potentiated CFTR and CaCCgie chloride channel activities in mouse colonic epithelia. Remarkably, the compounds showed inhibitory effects toward ANO1/CaCC-mediated short-circuit currents in ANO1/CaCC-expressing FRT cells, with IC50 values of 75 M for kobusin and 100 M for eudesmin. In charcoal transit study, both compounds mildly reduced gastrointestinal motility in mice. Taken together, these results revealed a new kind of activity displayed by the lignan compounds, one that is concerned with the modulation of chloride channel function
FMRI evidence for the interaction between orthography and phonology in reading Chinese compound words
No full textCompound words make up a major part of modern Chinese vocabulary. Behavioral studies have demonstrated that access to lexical semantics of compound words is driven by the interaction between orthographic and phonological information. However, little is known about the neural underpins of compound word processing. In this fMRI study, we asked participants to perform lexical decision to pseudohomophones, which were constructed by replacing one or both constituents of two-character compound words with orthographically dissimilar homophonic characters. Mixed pseudohomophones, which shared the first constituent with the base words, were more difficult to reject than non-pseudohomophone nonwords. This effect was accompanied by the increased activation of bilateral inferior frontal gyrus (IFG), left inferior parietal lobule (IPL), and left angular gyrus. The pure pseudohomophones, which shared no constituent with their base words, were rejected as quickly as nonword controls and did not elicit any significant neural activation. The effective connectivity of a phonological pathway from left IPL to left IFG was enhanced for the mixed pseudohomophones but not for pure pseudohomophones. These findings demonstrated that phonological activation alone, as in the case of the pure pseudohomophones, is not sufficient to drive access to lexical representations of compound words, and that orthographic information interacts with phonology, playing a gating role in the recognition of Chinese compound words
Activation of α7 nicotinic acetylcholine receptor decreases on-site mortality in crush syndrome through insulin signaling-Na/K-ATPase pathway
No full textOn-site mortality in crush syndrome remains high due to lack of effective drugs based on definite diagnosis. Anisodamine is widely used in China for treatment of shock, and activation of α7 nicotinic acetylcholine receptor (α7nAChR) mediates such antishock effect. The present work was designed to test whether activation of α7nAChR with anisodamine decreased mortality in crush syndrome shortly after decompression. Sprague-Dawley rats and C57BL/6 mice with crush syndrome were injected with anisodamine (20 mg/kg and 28 mg/kg respectively, i.p.) 30 min before decompression. Survival time, serum potassium, insulin, and glucose levels were observed shortly after decompression. Involvement of α7nAChR was verified with methyllycaconitine (selective α7nAChR antagonist) and PNU282987 (selective α7nAChR agonist), or in α7nAChR knockout mice. Effect of anisodamine was also appraised in C2C12 myotubes. Anisodamine reduced mortality and serum potassium and enhanced insulin sensitivity shortly after decompression in animals with crush syndrome, and PNU282987 exerted similar effects. Such effects were counteracted by methyllycaconitine or in α7nAChR knockout mice. Mortality and serum potassium in rats with hyperkalemia were also reduced by anisodamine. Phosphorylation of Na/K-ATPase was enhanced by anisodamine in C2C12 myotubes. Inhibition of tyrosine kinase on insulin receptor, phosphoinositide 3-kinase, mammalian target of rapamycin, signal transducer and activator of transcription 3, and Na/K-ATPase counteracted the effect of anisodamine on extracellular potassium. These findings demonstrated that activation of α7nAChR could decrease on-site mortality in crush syndrome, at least in part based on the decline of serum potassium through insulin signaling-Na/K-ATPase pathway
Stochastic Learning in Oxide Binary Synaptic Device for Neuromorphic Computing
No full textHardware implementation of neuromorphic computing is attractive as a computing paradigm beyond the conventional digital computing. In this work, we show that the SET (off-to-on) transition of metal oxide resistance switching memory becomes probabilistic under a weak programming condition. The switching variability of the binary synaptic device implements a stochastic learning rule. Such stochastic SET transition was statistically measured and modeled for a simulation of a winner-take-all network for competitive learning. The simulation illustrates that with such stochastic learning, the orientation classification function of input patterns can be effectively realized. The system performance metrics were compared between the conventional approach using the analog synapse and the approach in this work that employs the binary synapse utilizing the stochastic learning. The feasibility of using binary synapse in the neurormorphic computing may relax the constraints to engineer continuous multilevel intermediate states and widens the material choice for the synaptic device design
Immunization with Individual Proteins of the Lrp/AsnC Family Induces Protection Against Brucella melitensis 16M Challenges in Mice
No full textBrucellosis is one of the most common zoonoses worldwide. Subunit vaccines are promising for the prevention of human brucellosis. In our previous protective antigen screening studies, we identified a new protective antigen, BMEI0357, which belongs to the Lrp/asnC protein family, a conserved transcriptional regulator in bacteria that is absent in eukaryotes. In the present study, the Brucella genome annotation was screened and a total of 6 proteins were identified as members of the Lrp/AsnC family. Lrp/AsnC proteins have 2 domains that are conserved among the family members. However, sequence similarities between these proteins ranged from 9% to 50%, indicating high sequence heterogeneity. To test whether proteins of this family have similar characteristics, all 6 proteins were cloned and expressed in Escherichia coli. The recombinant proteins were purified and their protective efficacy was evaluated in BALB/c mice challenged with Brucella melitensis 16M. The results show that all 6 Lrp/AsnC proteins could induce a protective immune response against Brucella melitensis 16M. Antibodies against the Lrp/AsnC proteins were detected in the immunized mice. However, levels of antibodies against these proteins were relatively variable in human brucellosis sera. Taken together, our results show that these 6 proteins of the Lrp/AsnC family in Brucella could induce protective immune responses in mice
In vivo overexpression of X-linked inhibitor of apoptosis protein protects against neomycin-induced hair cell loss in the apical turn of the cochlea during the ototoxic-sensitive period
No full textAminoglycoside-induced cochlear ototoxicity causes hair cell (HC) loss and results in hearing impairment in patients. Previous studies have developed the concept of an ototoxicity-sensitive period during which the cochleae of young mice are more vulnerable to auditory trauma than adults. Here, we compared neomycin-induced ototoxicity at the following four developmental ages in mice: postnatal day (P)1–P7, P8–P14, P15–P21, and P60–P66. We found that when neomycin was administered between P8 and P14, the auditory brainstem response threshold increase was significantly higher at low frequencies and HC loss was significantly greater in the apical turn of the cochlea compared to neomycin administration during the other age ranges. qPCR data revealed that the expression of apoptotic markers, including Casp3 and Casp9, was significantly higher when neomycin was injected from P8 to P14, while the expression of the X-linked inhibitor of apoptosis protein (XIAP) gene was significantly higher when neomycin was injected from P60 to P66. Because XIAP expression was low during the neomycin-sensitive period, we overexpressed XIAP in mice and found that it could protect against neomycin-induced hearing loss at low frequencies and HC loss in the apical turn of the cochlea. Altogether, our findings demonstrate a protective role for XIAP against neomycin-induced hearing loss and HC loss in the apical turn of the cochlea during the ototoxic-sensitive period, and suggest that apoptotic factors mediate the effect of neomycin during the ototoxic-sensitive period
FvBck1, a Component of Cell Wall Integrity MAP Kinase Pathway, is Required for Virulence and Oxidative Stress Response in Sugarcane Pokkah Boeng Pathogen
No full textFusarium verticillioides (formerly F. moniliforme) is suggested as one of the causal agents of Pokkah Boeng, a serious disease of sugarcane worldwide. Currently, detailed molecular and physiological mechanism of pathogenesis is unknown. In this study, we focused on cell wall integrity MAPK pathway as one of the potential signaling mechanisms associated with Pokkah Boeng pathogenesis. We identified FvBCK1 gene that encodes a MAP kinase kinase kinase homolog and determined that it is not only required for growth, micro- and macro-conidia production, and cell wall integrity but also for response to osmotic and oxidative stresses. The deletion of FvBCK1 caused a significant reduction in virulence and FB1 production, a carcinogenic mycotoxin produced by the fungus. Moreover, we found the expression levels of three genes, which are known to be involved in superoxide scavenging, were down regulated in the mutant. We hypothesized that the loss of superoxide scavenging capacity was one of the reasons for reduced virulence, but overexpression of catalase or peroxidase gene failed to restore the virulence defect in the deletion mutant. When we introduced Magnaporthe oryzae MCK1 into the FvBck1 deletion mutant, while certain phenotypes were restored, the complemented strain failed to gain full virulence. In summary, FvBck1 plays a diverse role in F. verticillioides, and detailed investigation of downstream signaling pathways will lead to a better understanding of how this MAPK pathway regulates Pokkah Boeng on sugarcane
