| 3251. |
|
|
| 3252. |
- Liu, Ning-Ning, et al.
(författare)
-
Intersection of phosphate transport, oxidative stress and TOR signalling in Candida albicans virulence
- 2018
-
Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 14:7
-
Tidskriftsartikel (refereegranskat)abstract
- Phosphate is an essential macronutrient required for cell growth and division. Pho84 is the major high-affinity cell-surface phosphate importer of Saccharomyces cerevisiae and a crucial element in the phosphate homeostatic system of this model yeast. We found that loss of Candida albicans Pho84 attenuated virulence in Drosophila and murine oropharyngeal and disseminated models of invasive infection, and conferred hypersensitivity to neutrophil killing. Susceptibility of cells lacking Pho84 to neutrophil attack depended on reactive oxygen species (ROS): pho84-/- cells were no more susceptible than wild type C. albicans to neutrophils from a patient with chronic granulomatous disease, or to those whose oxidative burst was pharmacologically inhibited or neutralized. pho84-/- mutants hyperactivated oxidative stress signalling. They accumulated intracellular ROS in the absence of extrinsic oxidative stress, in high as well as low ambient phosphate conditions. ROS accumulation correlated with diminished levels of the unique superoxide dismutase Sod3 in pho84-/- cells, while SOD3 overexpression from a conditional promoter substantially restored these cells' oxidative stress resistance in vitro. Repression of SOD3 expression sharply increased their oxidative stress hypersensitivity. Neither of these oxidative stress management effects of manipulating SOD3 transcription was observed in PHO84 wild type cells. Sod3 levels were not the only factor driving oxidative stress effects on pho84-/- cells, though, because overexpressing SOD3 did not ameliorate these cells' hypersensitivity to neutrophil killing ex vivo, indicating Pho84 has further roles in oxidative stress resistance and virulence. Measurement of cellular metal concentrations demonstrated that diminished Sod3 expression was not due to decreased import of its metal cofactor manganese, as predicted from the function of S. cerevisiae Pho84 as a low-affinity manganese transporter. Instead of a role of Pho84 in metal transport, we found its role in TORC1 activation to impact oxidative stress management: overexpression of the TORC1-activating GTPase Gtr1 relieved the Sod3 deficit and ROS excess in pho84-/- null mutant cells, though it did not suppress their hypersensitivity to neutrophil killing or hyphal growth defect. Pharmacologic inhibition of Pho84 by small molecules including the FDA-approved drug foscarnet also induced ROS accumulation. Inhibiting Pho84 could hence support host defenses by sensitizing C. albicans to oxidative stress.
|
|
| 3253. |
|
|
| 3254. |
|
|
| 3255. |
- Liu, P., et al.
(författare)
-
Loss of menin in osteoblast lineage affects osteocyte-osteoclast crosstalk causing osteoporosis
- 2017
-
Ingår i: Cell Death and Differentiation. - : Springer Science and Business Media LLC. - 1350-9047 .- 1476-5403. ; 24:4, s. 672-682
-
Tidskriftsartikel (refereegranskat)abstract
- During osteoporosis bone formation by osteoblasts is reduced and/or bone resorption by osteoclasts is enhanced. Currently, only a few factors have been identified in the regulation of bone integrity by osteoblast-derived osteocytes. In this study, we show that specific disruption of menin, encoded by multiple endocrine neoplasia type 1 (Men1), in osteoblasts and osteocytes caused osteoporosis despite the preservation of osteoblast differentiation and the bone formation rate. Instead, an increase in osteoclast numbers and bone resorption was detected that persisted even when the deletion of Men1 was restricted to osteocytes. We demonstrate that isolated Men1-deficient osteocytes expressed numerous soluble mediators, such as C-X-C motif chemokine 10 (CXCL10), and that CXCL10-mediated osteoclastogenesis was reduced by CXCL10-neutralizing antibodies. Collectively, our data reveal a novel role for Men1 in osteocyte-osteoclast crosstalk by controlling osteoclastogenesis through the action of soluble factors. A role for Men1 in maintaining bone integrity and thereby preventing osteoporosis is proposed.
|
|
| 3256. |
- Liu, Peidi, et al.
(författare)
-
Transcriptomic and Proteomic Profiling Provides Insight into Mesangial Cell Function in IgA Nephropathy
- 2017
-
Ingår i: Journal of the American Society of Nephrology. - : AMER SOC NEPHROLOGY. - 1046-6673 .- 1533-3450. ; 28:10, s. 2961-2972
-
Tidskriftsartikel (refereegranskat)abstract
- IgA nephropathy (IgAN), the most common GN worldwide, is characterized by circulating galactose-deficient IgA (gd-IgA) that forms immune complexes. The immune complexes are deposited in the glomerular mesangium, leading to inflammation and loss of renal function, but the complete pathophysiology of the disease is not understood. Using an integrated global transcriptomic and proteomic profiling approach, we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsy specimens from patients with IgAN (n=19) and controls (n=22). Using curated glomerular cell type specific genes from the published literature, we found differential expression of a much higher percentage of mesangial cell positive standard genes than podocyte-positive standard genes in IgAN. Principal coordinate analysis of expression data revealed clear separation of patient and control samples on the basis of mesangial but not podocyte cell positive standard genes. Additionally, patient clinical parameters (serum creatinine values and eGFRs) significantly correlated with Z scores derived from the expression profile of mesangial cell positive standard genes. Among patients grouped according to Oxford MEST score, patients with segmental glomerulosclerosis had a significantly higher mesangial cell positive standard gene Z score than patients without segmental glomerulosclerosis. By investigating mesangial cell proteomics and glomerular transcriptomics, we identified 22 common pathways induced in mesangial cells by gd-IgA, most of which mediate inflammation. The genes, proteins, and corresponding pathways identified provide novel insights into the pathophysiologic mechanisms leading to IgAN.
|
|
| 3257. |
|
|
| 3258. |
- Liu, Q., et al.
(författare)
-
Functional characteristics of circulating granulocytes in severe congenital neutropenia caused by ELANE mutations
- 2019
-
Ingår i: Bmc Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 19
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundNeutrophils and eosinophils are multifunctional granulocytes derived from common myelocytic-committed progenitor cells. Severe congenital neutropenia 1 (SCN1) caused by ELANE mutations is a rare disease characterized by very low numbers of circulating neutrophils. Little is known about the functional characteristics of the SCN1 granulocytes, except that eosinophilia has been noticed in both bone marrow and peripheral blood. In this study, we profiled the number and function of granulocytes in patients suffering from SCN1.MethodsNine patients diagnosed with SCN1 were enrolled in this study and absolute counts of eosinophils and neutrophils from bone marrow aspirates and peripheral blood samples were analysed. In addition, Ficoll-Paque enriched granulocytes from patients and healthy controls were analysed for specific eosinophil and neutrophil markers using flow cytometry and for NADPH-oxidase activity-profile by chemiluminescence.ResultsOur data demonstrate a skewed granulocyte population in SCN1 patients dominated by eosinophils in both bone marrow and peripheral blood. The latter was detected only by blood smear examination, but not by automated blood analysers. Furthermore, we show that the SCN1 eosinophils exerted normal production of reactive oxygen species generated by the NADPH-oxidase, however the response was profoundly different from that of healthy control neutrophils.ConclusionsSCN1 patients with ELANE mutations suffer from neutropenia yet display eosinophilia in the bone marrow and blood, as revealed by smear examination but not by automatic blood analysers. The SCN1 eosinophils are functionally normal regarding production of reactive oxygen species (ROS). However, the ROS profile produced by eosinophils differs drastically from that of neutrophils isolated from the same blood donor, implying that the eosinophilia in SCN1 cannot compensate forthe loss of neutrophils regarding ROS-mediated functions.
|
|
| 3259. |
- Liu, Q., et al.
(författare)
-
High responsivity sensing of unfocused laser and white light using graphene photodetectors grown by chemical vapor deposition
- 2016
-
Ingår i: Optical Materials Express. - 2159-3930. ; 6:7, s. 2158-2164
-
Tidskriftsartikel (refereegranskat)abstract
- Graphene photodetectors grown by chemical vapor deposition are fabricated for unfocused laser and white light sensing. The unfocused light enlarges the illuminated graphene area and mimics the real-life sensing conditions, yielding a responsivity of 104 mA/W at room temperature without enhancing absorbance by waveguide and plasmonics. The devices are based on positive photoconductivity from the electron-hole photocarrier pairs and the bolometric-effect-induced negative photoconductivity. The buried off-center local gate induces a net internal potential in the graphene. The relative strength of the two photoconductivities depends on the gate voltage. The technology is scalable, which is a step ahead toward real applications.
|
|
| 3260. |
- Liu, Ruisheng, 1972-, et al.
(författare)
-
Ferromagnetic single-electron transistors fabricated by atomic force microscopy
- 2006
-
Konferensbidrag (refereegranskat)abstract
- We report on the fabrication and magneto-transport measurements of Ni/Au/Ni ferromagnetic single-electron transistors (F-SETs), fabricated by atomic force microscopy. By positioning a single Au disc (30 nm in diameter) into the gap between the Ni drain and source electrodes (of width 220 nm and 80 nm, respectively) step-by-step with Angstrom precision, and using plasma-processed NiOx as tunneling barriers, we can successfully fabricate F-SETs of high quality and substantial stability. The characteristic time interval of the device between two successive tunneling events is 10ps. The absence of any clear features in the transport related to the applied external magnetic field indicates that no spin-accumulation is maintained in the central Au disc. This interesting result indicates that the spin-relaxation time inside the central island should be shorter than 10ps. Based on these findings, we will discuss possible mechanisms of spin-relaxation in metal nano-structures triggered by spin-orbit interaction.
|
|
