Mordell-Weil Lattice via String Junctions

We analyze the structure of singularities, Mordell-Weil lattices and torsions of a rational elliptic surface using string junctions in the background of 12 7-branes. The classification of the Mordell-Weil lattices due to Oguiso-Shioda is reproduced in terms of the junction lattice. In this analysis an important role played by the global structure of the surface is observed. It is then found that the torsions in the Mordell-Weil group are generated by the fraction of loop junctions which represent the imaginary roots of the loop algebra $\hat E_9$. From the structure of the Mordell-Weil lattice we find 7-brane configurations which support non-BPS junctions carrying conserved Abelian charges.Comment: 35 pages, Latex, 3 figure

Advanced Glycation End Products Induce PeroxisomeProliferator-Activated Receptor c Down-Regulation-Related Inflammatory Signals in Human Chondrocytesvia Toll-Like Receptor-4 and Receptor for AdvancedGlycation End Products

Accumulation of advanced glycation end products (AGEs) in joints is important in the development of cartilage destruction and damage in age-related osteoarthritis (OA). The aim of this study was to investigate the roles of peroxisome proliferator-activated receptor γ (PPARγ), toll-like receptor 4 (TLR4), and receptor for AGEs (RAGE) in AGEs-induced inflammatory signalings in human OA chondrocytes. Human articular chondrocytes were isolated and cultured. The productions of metalloproteinase-13 and interleukin-6 were quantified using the specific ELISA kits. The expressions of related signaling proteins were determined by Western blotting. Our results showed that AGEs enhanced the productions of interleukin-6 and metalloproteinase-13 and the expressions of cyclooxygenase-2 and high-mobility group protein B1 and resulted in the reduction of collagen II expression in human OA chondrocytes. AGEs could also activate nuclear factor (NF)-κB activation. Stimulation of human OA chondrocytes with AGEs significantly induced the up-regulation of TLR4 and RAGE expressions and the down-regulation of PPARγ expression in a time- and concentration-dependent manner. Neutralizing antibodies of TLR4 and RAGE effectively reversed the AGEs-induced inflammatory signalings and PPARγ down-regulation. PPARγ agonist pioglitazone could also reverse the AGEs-increased inflammatory signalings. Specific inhibitors for p38 mitogen-activated protein kinases, c-Jun N-terminal kinase and NF-κB suppressed AGEs-induced PPARγ down-regulation and reduction of collagen II expression. Taken together, these findings suggest that AGEs induce PPARγ down-regulation-mediated inflammatory signalings and reduction of collagen II expression in human OA chondrocytes via TLR4 and RAGE, which may play a crucial role in the development of osteoarthritis pathogenesis induced by AGEs accumulation

Affine 7-brane Backgrounds and Five-Dimensional ENE_N Theories on S1S^1

Elliptic curves for the 7-brane configurations realizing the affine Lie algebras \wh E_n $(1 \leq n \leq 8)$ and \wh{\wt E}_n $(n=0,1)$ are systematically derived from the cubic equation for a rational elliptic surface. It is then shown that the \wh E_n 7-branes describe the discriminant locus of the elliptic curves for five-dimensional (5D) N=1 $E_n$ theories compactified on a circle. This is in accordance with a recent construction of 5D N=1 $E_n$ theories on the IIB 5-brane web with 7-branes, and indicates the validity of the D3 probe picture for 5D $E_n$ theories on \bR^4 \times S^1. Using the \wh E_n curves we also study the compactification of 5D $E_n$ theories to four dimensions.Comment: 23 pages, Latex, no figures, some statements clarified, typos corrected, references and note adde

WNK1-OSR1 kinase-mediated phospho-activation of Na+-K+-2Cl- cotransporter facilitates glioma migration

Background: The bumetanide (BMT)-sensitive Na+-K+-2Cl- cotransporter isoform 1 (NKCC1) maintains cell volume homeostasis by increasing intracellular K+ and Cl- content via regulatory volume increase (RVI). Expression levels of NKCC1 positively correlate with the histological grade and severity of gliomas, the most common primary adult brain tumors, and up-regulated NKCC1 activity facilitates glioma cell migration and apoptotic resistance to the chemotherapeutic drug temozolomide (TMZ). However, the cellular mechanisms underlying NKCC1 functional up-regulation in glioma and in response to TMZ administration remain unknown. Methods: Expression of NKCC1 and its upstream kinases With-No-K (Lysine) kinase 1 (WNK1) and oxidative stress-responsive kinase-1 (OSR1) in different human glioma cell lines and glioma specimens were detected by western blotting and immunostaining. Live cell imaging and microchemotaxis assay were applied to record glioma cell movements under different treatment conditions. Fluorescence indicators were utilized to measure cell volume, intracellular K+ and Cl- content to reflect the activity of NKCC1 on ion transportation. Small interfering RNA (siRNA)-mediated knockdown of WNK1 or OSR1 was used to explore their roles in regulation of NKCC1 activity in glioma cells. Results of different treatment groups were compared by one-way ANOVA using the Bonferroni post-hoc test in the case of multiple comparisons. Results: We show that compared to human neural stem cells and astrocytes, human glioma cells exhibit robust increases in the activation and phosphorylation of NKCC1 and its two upstream regulatory kinases, WNK1 and OSR1. siRNA-mediated knockdown of WNK1 or OSR1 reduces intracellular K+ and Cl- content and RVI in glioma cells by abolishing NKCC1 regulatory phospho-activation. Unexpectedly, TMZ activates the WNK1/OSR1/NKCC1 signaling pathway and enhances glioma migration. Pharmacological inhibition of NKCC1 with its potent inhibitor BMT or siRNA knockdown of WNK1 or OSR1 significantly decreases glioma cell migration after TMZ treatment. Conclusion: Together, our data show a novel role for the WNK1/OSR1/NKCC1 pathway in basal and TMZ-induced glioma migration, and suggest that glioma treatment with TMZ might be improved by drugs that inhibit elements of the WNK1/OSR1/NKCC1 signaling pathway

Urinary Extracellular Vesicles for Renal Tubular Transporters Expression in Patients With Gitelman Syndrome

Background: The utility of urinary extracellular vesicles (uEVs) to faithfully represent the changes of renal tubular protein expression remains unclear. We aimed to evaluate renal tubular sodium (Na+) or potassium (K+) associated transporters expression from uEVs and kidney tissues in patients with Gitelman syndrome (GS) caused by inactivating mutations in SLC12A3.Methods: uEVs were isolated by ultracentrifugation from 10 genetically-confirmed GS patients. Membrane transporters including Na+-hydrogen exchanger 3 (NHE3), Na+/K+/2Cl− cotransporter (NKCC2), NaCl cotransporter (NCC), phosphorylated NCC (p-NCC), epithelial Na+ channel β (ENaCβ), pendrin, renal outer medullary K1 channel (ROMK), and large-conductance, voltage-activated and Ca2+-sensitive K+ channel (Maxi-K) were examined by immunoblotting of uEVs and immunofluorescence of biopsied kidney tissues. Healthy and disease (bulimic patients) controls were also enrolled.Results: Characterization of uEVs was confirmed by nanoparticle tracking analysis, transmission electron microscopy, and immunoblotting. Compared with healthy controls, uEVs from GS patients showed NCC and p-NCC abundance were markedly attenuated but NHE3, ENaCβ, and pendrin abundance significantly increased. ROMK and Maxi-K abundance were also significantly accentuated. Immunofluorescence of the representative kidney tissues from GS patients also demonstrated the similar findings to uEVs. uEVs from bulimic patients showed an increased abundance of NCC and p-NCC as well as NHE3, NKCC2, ENaCβ, pendrin, ROMK and Maxi-K, akin to that in immunofluorescence of their kidney tissues.Conclusion: uEVs could be a non-invasive tool to diagnose and evaluate renal tubular transporter adaptation in patients with GS and may be applied to other renal tubular diseases

Duality Between String Junctions and D-Branes on Del Pezzo Surfaces

We revisit local mirror symmetry associated with del Pezzo surfaces in Calabi-Yau threefolds in view of five-dimensional N=1 E_N theories compactified on a circle. The mirror partner of singular Calabi-Yau with a shrinking del Pezzo four-cycle is described as the affine 7-brane backgrounds probed by a D3-brane. Evaluating the mirror map and the BPS central charge we relate junction charges to RR charges of D-branes wrapped on del Pezzo surfaces. This enables us to determine how the string junctions are mapped to D-branes on del Pezzo surfaces.Comment: 35 pages, Latex, 1 figure; typos corrected, references update

Acute kidney disease following COVID-19 vaccination: a single-center retrospective study

BackgroundRare cases of de novo or relapsed kidney diseases associated with vaccination against coronavirus disease 2019 (COVID-19) have been increasingly reported. The aim of this study was to report the incidence, etiologies, and outcomes of acute kidney disease (AKD) following COVID-19 vaccination.MethodsThis retrospective study extracted cases from renal registry of a single medical center from 1 March 2021 to 30 April 2022, prior to the significant surge in cases of the Omicron variant of COVID-19 infection in Taiwan. Adult patients who developed AKD after COVID-19 vaccination were included. We utilized the Naranjo score as a causality assessment tool for adverse vaccination reactions and charts review by peer nephrologists to exclude other causes. The etiologies, characteristics, and outcomes of AKD were examined.ResultsTwenty-seven patients (aged 23 to 80 years) with AKD were identified from 1,897 vaccines (estimated rate of 13.6 per 1000 patient-years within the renal registry). A majority (77.8%) of vaccine received messenger RNA-based regimens. Their median (IQR) Naranjo score was 8 (6-9) points, while 14 of them (51.9%) had a definite probability (Naranjo score ≥ 9). The etiologies of AKD included glomerular disease (n = 16) consisting of seven IgA nephropathy, four anti-neutrophil cytoplasmic antibodies-associated glomerulonephritis (AAN), three membranous glomerulonephritis, two minimal change diseases, and chronic kidney disease (CKD) with acute deterioration (n = 11). Extra-renal manifestations were found in four patients. Over a median (IQR) follow-up period of 42 (36.5–49.5) weeks, six patients progressed to end-stage kidney disease (ESKD).ConclusionBesides glomerulonephritis (GN), the occurrence of AKD following COVID-19 vaccination may be more concerning in high-risk CKD patients receiving multiple doses. Patients with the development of de novo AAN, concurrent extra-renal manifestations, or pre-existing moderate to severe CKD may exhibit poorer kidney prognosis

The control of postharvest blue and green molds of citrus in relation with essential oil-wax formulations, adherence and viscosity.

peer reviewedThe use of wax coatings enriched with antifungals has significantly contributed to quality maintaining of harvested citrus fruit. On the other hand, interest in essential oils (EOs) as an alternative to synthetic fungicides has recently gained momentum. In this study, Cinnamomum zeylanicum EO was incorporated into a variety of commercial citrus waxes (shellac, carnauba, paraffin and polyethylene). The biological activity of these formulations against green and blue rots as well as their viscosity and adherence to the orange fruit surface were evaluated. Excellent disease control was achieved with C. zeylanicum EO incorporated in shellac and/or carnauba wax compared to other EO–wax formulations. Disease control by EO–waxes seems to depend not only on the volume that remains on the fruit skin, but also, probably on the retention of EO components on the fruit. Other factors such as formulation solubility, permeability to gases, and compatibility between EO compounds and those of waxes may also be involved in the improvement of EO efficacy. The present study may therefore allow a careful selection of ppropriate waxes for the elaboration of effective EO–wax formulations

Establishing and evaluating FRAX® probability thresholds in Taiwan

Background/purpose: The Taiwanese FRAX® calculator was launched in 2010. However, cost-effectiveness thresholds for the prescription of antiosteoporosis medications were not established. This study aims to establish and evaluate FRAX®-based probability thresholds in Taiwan. Methods: Using previous data from Taiwan and literature, we determined cost-effectiveness thresholds for prevention of osteoporotic fractures by alendronate with a Markov model, as well as using two other translational approaches. Sensitivity analysis was applied using different alendronate prices. A clinical sample was used to test these Taiwan-specific thresholds by determining the percentages of high-risk patients who would be qualified for current National Health Insurance reimbursement. Results: With the Markov model, the intervention threshold for hip fracture was 7% for women and 6% for men; for major osteoporotic fracture, it was 15% for women and 12.5% for men. Both translational approach models were cost effective only for certain age groups. However, if branded alendronate was reimbursed at 60% of the current price, they became cost effective in almost all age groups. This clinical screening study showed that the National Health Insurance Administration model identified the highest proportion (44%) of patients qualified for National Health Insurance reimbursements, followed by the Markov model (30%), and the United States model (22%). Conclusion: Three FRAX®-based models of alendronate use were established in Taiwan to help optimize treatment strategies. The government is encouraged to incorporate FRAX®-based approaches into the reimbursement policy for antiosteoporosis medicines