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1.
Sci Rep ; 14(1): 16274, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39009614

ABSTRACT

The α-helical antimicrobial peptide Kn2-7 enhances the activation of mouse macrophage-like RAW264.7 induced by DNA containing unmethylated cytosine-guanine motifs (CpG DNA). This enhancement is related to increased cellular uptake of DNA by Kn2-7, but the relevant properties of Kn2-7 are unknown. Physicochemical property analysis revealed that Kn2-7 has high amphipathicity. In contrast, the α-helical antimicrobial peptide L5, which increases the cellular uptake of CpG DNA but does not enhance CpG DNA-induced activation, has low amphipathicity. Kn2-7 derivatives with decreased amphipathicity but the same amino acid composition as Kn2-7 did not enhance CpG DNA-induced activation. On the other hand, L5 derivatives with high amphipathicity but the same amino acid composition as L5 enhanced CpG DNA-induced activation. Cellular uptake of DNA was not increased by the L5 derivatives, indicating that high amphipathicity does not affect DNA uptake. Furthermore, α-helical peptides with reversed sequences relative to the Kn2-7 and L5 derivatives with high amphipathicity were synthesized. The reversed-sequence peptides, which had the same amphipathicity but different amino acid sequences from their counterparts, enhanced CpG DNA-induced activation. Taken together, these observations indicate that the high amphipathicity of α-helical peptides enhances the CpG DNA-induced activation of RAW264.7.


Subject(s)
CpG Islands , Macrophages , Animals , Mice , RAW 264.7 Cells , Macrophages/drug effects , Macrophages/metabolism , DNA/chemistry , DNA/metabolism , Macrophage Activation/drug effects , Protein Conformation, alpha-Helical , DNA Methylation/drug effects , Peptides/chemistry , Peptides/pharmacology , Antimicrobial Peptides/pharmacology , Antimicrobial Peptides/chemistry
2.
Commun Biol ; 7(1): 746, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38898124

ABSTRACT

DNA methylation maintenance is essential for cell fate inheritance. In differentiated cells, this involves orchestrated actions of DNMT1 and UHRF1. In mice, the high-affinity binding of DPPA3 to the UHRF1 PHD finger regulates UHRF1 chromatin dissociation and cytosolic localization, which is required for oocyte maturation and early embryo development. However, the human DPPA3 ortholog functions during these stages remain unclear. Here, we report the structural basis for human DPPA3 binding to the UHRF1 PHD finger. The conserved human DPPA3 85VRT87 motif binds to the acidic surface of UHRF1 PHD finger, whereas mouse DPPA3 binding additionally utilizes two unique α-helices. The binding affinity of human DPPA3 for the UHRF1 PHD finger was weaker than that of mouse DPPA3. Consequently, human DPPA3, unlike mouse DPPA3, failed to inhibit UHRF1 chromatin binding and DNA remethylation in Xenopus egg extracts effectively. Our data provide novel insights into the distinct function and structure of human DPPA3.


Subject(s)
CCAAT-Enhancer-Binding Proteins , Ubiquitin-Protein Ligases , Animals , Humans , Mice , Amino Acid Sequence , CCAAT-Enhancer-Binding Proteins/metabolism , CCAAT-Enhancer-Binding Proteins/genetics , CCAAT-Enhancer-Binding Proteins/chemistry , Chromatin/metabolism , DNA Methylation , PHD Zinc Fingers/genetics , Protein Binding , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/chemistry , Xenopus laevis/metabolism
3.
Clin Exp Nephrol ; 27(2): 141-150, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36329296

ABSTRACT

BACKGROUND: Fabry disease (FD) is an X-linked inherited disease where renal complications are associated with a poor prognosis. However, little is known about the prevalence of Fabry nephropathy (FN) in patients with chronic kidney disease (CKD). We extracted FN data from the Japan Renal Biopsy Registry, analyzed the prevalence of FN, and examined the correlation between clinical characteristics and renal involvement according to sex differences and hemi- and heterozygosity in patients with FD. METHODS: A total of 38,351 participants who underwent renal biopsy were retrospectively enrolled, and FN was determined. The clinical characteristics of FD patients were examined based on sex differences. RESULTS: Twenty-nine patients (0.076%) (19 males and 10 females, mean age: 43.7 ± 15.5 years old) were diagnosed with FN. Median estimated urinary protein (UP) and mean eGFR levels were 0.9 [interquartile range (IQR) [0.7-1.6] g/gCr and 67.1 ± 36.8 mL/min/1.73 m2, respectively. Mean systolic blood pressure (SBP) was 126.4 ± 17.1 mmHg and diastolic blood pressure was 76.1 ± 12.6 mmHg. An inverse correlation between eGFR and logarithm UP levels was observed (r2 = 0.23, p = 0.02), SBP was positively associated with logarithm UP (r2 = 0.34, p = 0.004) overall and inversely associated with eGFR (r2 = 0.25, p = 0.007) regardless of sex, and SBP was an independent determinant of proteinuria (p = 0.004) and eGFR (p = 0.007). CONCLUSIONS: The prevalence of biopsy-proven FN was 0.076%. Since SBP is associated with eGFR regardless of zygosity, strict SBP control might be necessary to prevent progression to end-stage kidney disease in both male and female patients with FN.


Subject(s)
Fabry Disease , Renal Insufficiency, Chronic , Adult , Female , Humans , Male , Middle Aged , Biopsy , Cross-Sectional Studies , Fabry Disease/complications , Fabry Disease/diagnosis , Fabry Disease/epidemiology , Glomerular Filtration Rate , Japan/epidemiology , Registries , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/etiology , Retrospective Studies
5.
Int J Mol Sci ; 22(13)2021 Jun 27.
Article in English | MEDLINE | ID: mdl-34198993

ABSTRACT

Mechanistic target of rapamycin complex 1 (mTORC1) is a master growth regulator by controlling protein synthesis and autophagy in response to environmental cues. Amino acids, especially leucine and arginine, are known to be important activators of mTORC1 and to promote lysosomal translocation of mTORC1, where mTORC1 is thought to make contact with its activator Rheb GTPase. Although amino acids are believed to exclusively regulate lysosomal translocation of mTORC1 by Rag GTPases, how amino acids increase mTORC1 activity besides regulation of mTORC1 subcellular localization remains largely unclear. Here we report that amino acids also converge on regulation of the TSC2-Rheb GTPase axis via Ca2+/calmodulin (CaM). We showed that the amino acid-mediated increase of intracellular Ca2+ is important for mTORC1 activation and thereby contributes to the promotion of nascent protein synthesis. We found that Ca2+/CaM interacted with TSC2 at its GTPase activating protein (GAP) domain and that a CaM inhibitor reduced binding of CaM with TSC2. The inhibitory effect of a CaM inhibitor on mTORC1 activity was prevented by loss of TSC2 or by an active mutant of Rheb GTPase, suggesting that a CaM inhibitor acts through the TSC2-Rheb axis to inhibit mTORC1 activity. Taken together, in response to amino acids, Ca2+/CaM-mediated regulation of the TSC2-Rheb axis contributes to proper mTORC1 activation, in addition to the well-known lysosomal translocation of mTORC1 by Rag GTPases.


Subject(s)
Amino Acids/metabolism , Calcium Signaling , Calcium/metabolism , Calmodulin/metabolism , Mechanistic Target of Rapamycin Complex 1/metabolism , Ras Homolog Enriched in Brain Protein/metabolism , Tuberous Sclerosis Complex 2 Protein/metabolism , Cell Line , Gene Knockdown Techniques , Humans , Intracellular Space/metabolism , Lysosomes/metabolism , Models, Biological , Protein Binding , Signal Transduction
6.
Nephrol Dial Transplant ; 37(1): 115-125, 2021 12 31.
Article in English | MEDLINE | ID: mdl-34282462

ABSTRACT

BACKGROUND: Fabry disease (FD), an X-linked lysosomal storage disorder caused by a deficiency in alfa-galactosidase A (α-Gal A) activity due to mutations in the GLA gene, has a prevalence of 0-1.69% in patients undergoing haemodialysis; however, its prevalence in patients with chronic kidney disease (CKD) Stages 1-5 is unknown. METHODS: Serum α-Gal A activity analysis and direct sequencing of GLA were used to screen for FD in 2122 male patients with CKD, including 1703 patients with CKD Stage 5D and 419 with CKD Stages 1-5. The correlation between serum α-Gal A activity and confounding factors in patients with CKD Stages 1-5 was evaluated. RESULTS: FD prevalence rates in patients with CKD Stage 5D and CKD Stages 1-5 were 0.06% (1/1703) and 0.48% (2/419), respectively. A patient with CKD Stage 5D exhibited a novel GLA mutation, p.Met208Arg, whereas two patients with CKD Stages 1-5 had c.370delG and p.Met296Ile. p. Met208Arg caused moderate structural changes in the molecular surface region near the substituted amino acid residue but did not affect the catalytic residues Asp170 and Asp231 in α-Gal A. Serum α-Gal A activity in patients with CKD Stages 1-5 was inversely correlated with age (P < 0.0001) but directly correlated with estimated glomerular filtration rate (P < 0.0001). CONCLUSIONS: FD prevalence was much higher in male patients with CKD Stages 1-5 than in those with CKD Stage 5D. FD screening in patients with CKD Stages 1-5 may improve patient survival, decreasing the number of patients with CKD Stage 5D.


Subject(s)
Fabry Disease , Renal Insufficiency, Chronic , Fabry Disease/complications , Fabry Disease/diagnosis , Fabry Disease/epidemiology , Humans , Japan/epidemiology , Male , Mutation , Renal Dialysis , Renal Insufficiency, Chronic/epidemiology , alpha-Galactosidase/genetics
7.
Sci Total Environ ; 782: 146854, 2021 Aug 15.
Article in English | MEDLINE | ID: mdl-33853007

ABSTRACT

Temperature and oxygen limit the distribution of marine ectotherms. Haematological traits underlying blood-oxygen carrying capacity are thought to be correlated with thermal tolerance in certain fishes, and this relationship is hypothesised to be explained by oxygen supply capacity. We tested this hypothesis using reef shark neonates as experimental models because they live near their upper thermal limits and are physiologically sensitive to low oxygen conditions. We first described in situ associations between temperature and oxygen at the study site (Moorea, French Polynesia) and found that the habitats for reef shark neonates (Carcharhinus melanopterus and Negaprion acutidens) were hyperoxic at the maximum recorded temperatures. Next, we tested for in situ associations between thermal habitat characteristics and haematological traits of neonates. Contrary to predictions, we only demonstrated a negative association between haemoglobin concentration and maximum habitat temperatures in C. melanopterus. Next, we tested for ex situ associations between critical thermal maximum (CTMax) and haematological traits, but only demonstrated a negative association between haematocrit and CTMax in C. melanopterus. Finally, we measured critical oxygen tension (pcrit) ex situ and estimated its temperature sensitivity to predict oxygen-dependent values of CTMax. Estimated temperature sensitivity of pcrit was similar to reported values for sharks and skates, and predicted values for CTMax equalled maximum habitat temperatures. These data demonstrate unique associations between haematological traits and thermal tolerance in a reef shark that are likely not explained by oxygen supply capacity. However, a relationship between oxygen supply capacity and thermal tolerance remains to be demonstrated empirically.


Subject(s)
Sharks , Animals , Ecosystem , Humans , Infant, Newborn , Oxygen , Polynesia , Temperature
8.
Conserv Biol ; 35(2): 598-609, 2021 04.
Article in English | MEDLINE | ID: mdl-32681546

ABSTRACT

Managing human use of ecosystems in an era of rapid environmental change requires an understanding of diverse stakeholders' behaviors and perceptions to enable effective prioritization of actions to mitigate multiple threats. Specifically, research examining how threat perceptions are shared or diverge among stakeholder groups and how these can evolve through time is increasingly important. We investigated environmental threat perceptions related to Australia's Great Barrier Reef and explored their associations before and after consecutive years of mass coral bleaching. We used data from surveys of commercial fishers, tourism operators, and coastal residents (n = 5254) conducted in 2013 and 2017. Threats perceived as most serious differed substantially among groups before bleaching but were strongly aligned after bleaching. Climate change became the most frequently reported threat by all stakeholder groups following the coral bleaching events, and perceptions of fishing and poor water quality as threats also ranked high. Within each of the 3 stakeholder groups, fishers, tourism operators, and coastal residents, the prioritization of these 3 threats tended to diverge in 2013, but convergence occurred after bleaching. These results indicate an emergence of areas of agreement both within and across stakeholder groups. Changes in perceptions were likely influenced by high-profile environmental-disturbance events and media representations of threats. Our results provide insights into the plasticity of environmental-threat perceptions and highlight how their convergence in response to major events may create new opportunities for strategic public engagement and increasing support for management.


Convergencia de la Percepción de las Amenazas Ambientales por los Actores Sociales después del Blanqueamiento Masivo del Coral de la Gran Barrera Arrecifal Resumen La administración del uso que las personas dan a los ecosistemas en una época de cambios ambientales rápidos requiere un entendimiento del comportamiento de diferentes actores sociales y sus percepciones para facilitar la priorización de las acciones que mitigan a las múltiples amenazas. Específicamente, las investigaciones que examinan cómo se comparten o difieren las percepciones de las amenazas entre los grupos de actores y cómo estas percepciones pueden evolucionar con el tiempo son cada vez más importantes. Investigamos las percepciones de las amenazas ambientales relacionadas con la Gran Barrera Arrecifal en Australia y exploramos sus asociaciones antes y después de varios años consecutivos de blanqueamiento masivo del coral. Usamos datos tomados de encuestas realizadas a pescadores comerciales, operadores turísticos y residentes de la costa (n = 5,254) en 2013 y 2017. Las amenazas percibidas como las más serias difirieron sustancialmente entre los tres grupos antes del blanqueamiento, pero se alinearon marcadamente después del blanqueamiento. El cambio climático se convirtió en la amenaza reportada con mayor frecuencia por todos los grupos de actores después de los eventos de blanqueamiento del coral. Las percepciones de la pesca y la baja calidad del agua como amenazas también tuvieron una clasificación alta. Dentro de cada uno de los tres grupos de actores (pescadores, operadores turísticos y residentes de la costa) la priorización de estas tres amenazas tendió a diferir en 2013 pero la convergencia ocurrió después del blanqueamiento. Estos resultados indican un surgimiento de áreas de acuerdo dentro y entre los grupos de actores. Los cambios en las percepciones probablemente estuvieron influenciados por eventos de perturbación ambiental de alto perfil y la representación mediática de las amenazas. Nuestros resultados proporcionaron conocimiento sobre la plasticidad de las percepciones de las amenazas ambientales y resalta cómo su convergencia en la respuesta a los eventos más importantes puede crear nuevas oportunidades para la participación estratégica del público e incrementar el apoyo para su manejo.


Subject(s)
Anthozoa , Animals , Climate Change , Conservation of Natural Resources , Coral Reefs , Ecosystem , Humans , Perception
9.
Clin Exp Nephrol ; 25(3): 251-260, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33141305

ABSTRACT

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder caused by mutations in the polycystic kidney disease (PKD) gene. Although tolvaptan has benefits for renal involvement, the different effects depending on the gene mutation type are unknown. Thus, we explore the different effects of tolvaptan on the annual changes in total kidney volume (%TKV) and estimated glomerular filtration rate (eGFR) according to the gene mutation type in ADPKD patients. METHODS: In total, 135 ADPKD patients were screened, and 22 patients taking tolvaptan for at least a year were retrospectively studied at the Kurume University Hospital. We examined the decline in renal function and %TKV by computed tomography and analyzed the gene mutation. Patients were classified into the following four groups according to gene mutation type: PKD1-truncated, PKD1-non-truncated, PKD2, and mutation not found. Patients were treated with tolvaptan, and the effects of tolvaptan were analyzed according to the gene mutation type. RESULTS: Patients (age: 52.3 ± 11.2 years) were administered tolvaptan at a dose of 45 or 60 mg. No variation was observed in the annual changes in eGFR (%eGFR) (before: - 10.5% ± 13.9%, after: - 14.4% ± 8.1%, P = 0.139), whereas %TKV was significantly improved after the tolvaptan treatment (before: 14.9% ± 8.0%, after: - 5.4% ± 7.6%, P < 0.001). Unlike %eGFR, tolvaptan treatment significantly improved %TKV, regardless of the type of gene mutation. CONCLUSIONS: A year treatment with tolvaptan significantly improved %TKV in patients with ADPKD, regardless of the gene mutation type.


Subject(s)
Antidiuretic Hormone Receptor Antagonists/therapeutic use , Kidney/drug effects , Mutation , Polycystic Kidney, Autosomal Dominant/drug therapy , TRPP Cation Channels/genetics , Tolvaptan/therapeutic use , Adult , Aged , Female , Genetic Predisposition to Disease , Glomerular Filtration Rate/drug effects , Humans , Kidney/diagnostic imaging , Kidney/physiopathology , Male , Middle Aged , Polycystic Kidney, Autosomal Dominant/diagnosis , Polycystic Kidney, Autosomal Dominant/genetics , Polycystic Kidney, Autosomal Dominant/physiopathology , Recovery of Function , Retrospective Studies , Time Factors , Tomography, X-Ray Computed , Treatment Outcome
10.
Infect Immun ; 88(6)2020 05 20.
Article in English | MEDLINE | ID: mdl-32284369

ABSTRACT

Salmonella enterica serovar Typhimurium is an important foodborne pathogen that causes diarrhea. S. Typhimurium elicits inflammatory responses and colonizes the gut lumen by outcompeting the microbiota. Although evidence is accumulating with regard to the underlying mechanism, the infectious stage has not been adequately defined. Peptidoglycan amidases are widely distributed among bacteria and play a prominent role in peptidoglycan maintenance by hydrolyzing peptidoglycans. Amidase activation is required for the regulation of at least one of two cognate activators, NlpD or EnvC (also called YibP). Recent studies established that the peptidoglycan amidase AmiC-mediated cell division specifically confers a fitness advantage on S Typhimurium in the inflamed gut. However, it remains unknown which cognate activators are involved in the amidase activation and how the activators influence Salmonella sp. pathogenesis. Here, we characterize the role of two activators, NlpD and EnvC, in S Typhimurium cell division and gut infection. EnvC was found to contribute to cell division of S Typhimurium cells through the activation of AmiA and AmiC. The envC mutant exhibited impairments in gut infection, including a gut colonization defect and reduced ability to elicit inflammatory responses. Importantly, the colonization defect of the envC mutant was unrelated to the microbiota but was conferred by attenuated motility and chemotaxis of S Typhimurium cells, which were not observed in the amiA amiC mutant. Furthermore, the envC mutant was impaired in its induction of mucosal inflammation and sustained gut colonization. Collectively, our findings provide a novel insight into the peptidoglycan amidase/cognate activator circuits and their dependent pathogenesis.


Subject(s)
Bacterial Proteins/metabolism , N-Acetylmuramoyl-L-alanine Amidase/metabolism , Salmonella Infections/microbiology , Salmonella typhimurium/physiology , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Deoxycholic Acid/pharmacology , Escherichia coli/physiology , Lipoproteins/genetics , Lipoproteins/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism , Microbial Sensitivity Tests , Models, Biological , Mutation , N-Acetylmuramoyl-L-alanine Amidase/genetics , Salmonella typhimurium/drug effects
11.
BMC Nephrol ; 20(1): 469, 2019 12 17.
Article in English | MEDLINE | ID: mdl-31847900

ABSTRACT

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations of the GLA gene, followed by deficiency in α-galactosidase A (α-gal) activity. Nephrotic syndrome, as the renal phenotype of FD, is unusual. Here, we report the rare case of a patient with FD with nephrotic syndrome whose proteinuria disappeared by immunotherapy. CASE PRESENTATION: A 67-year-old Japanese man was admitted to our hospital because of emesis, abdominal pain, and facial edema due to nephrotic syndrome. The patient was diagnosed with focal segmental glomerulosclerosis (FSGS) by renal biopsy before being diagnosed with FD, and immunotherapy was initiated. After treatment, the kidney biopsy results showed typical glycosphingolipid accumulation in the podocytes of this patient. The white blood cell α-gal activity was very low, and genetic analysis revealed a GLA gene variant (M296I), which is known as a late-onset genetic mutation of FD. Immunotherapy (steroids and cyclosporine A) dramatically improved the massive proteinuria. Currently, he has been undergoing enzyme replacement therapy, and his proteinuria has further decreased. There is the possibility that other nephrotic syndromes, such as minimal change nephrotic syndrome or FSGS, may co-exist in this patient. CONCLUSIONS: We experienced the rare case of a FD patient whose nephrotic syndrome disappeared by immunotherapy. These findings suggest that immunosuppressive treatment may be considered if nephrotic syndrome develops, even in patients with FD.


Subject(s)
Fabry Disease/blood , Fabry Disease/drug therapy , Immunosuppressive Agents/therapeutic use , Nephrotic Syndrome/blood , Nephrotic Syndrome/drug therapy , Aged , Fabry Disease/complications , Humans , Male , Nephrotic Syndrome/complications , Treatment Outcome
12.
CEN Case Rep ; 8(3): 205-211, 2019 08.
Article in English | MEDLINE | ID: mdl-30927247

ABSTRACT

A 65-year-old male patient with nephrotic syndrome was admitted to our hospital due to worsening systemic edema and purpura on the limbs. He had an impaired renal function, low serum complement level, and elevated rheumatoid factor level. He was positive for cryoglobulin (monoclonal IgM-κ and polyclonal mixed-type IgG), and the results of his kidney biopsy showed a tissue profile of membranoproliferative glomerulonephritis (MPGN). Due to the fact that the secondary cause was unclear, he was diagnosed with MPGN due to essential mixed cryoglobulinemia. On hospital day 20, he was initiated on 50 mg/day prednisolone (PSL). On hospital day 43, oral mizoribine (MZR) at a dose of 150 mg/day was prescribed. On hospital day 49, cryofiltration was performed because the disease was steroid resistant. The treatment promptly decreased urine protein levels. Serum albumin and serum complement levels increased, and complete remission was achieved approximately three months after the initiation of treatment. The PSL and MZR doses were gradually reduced to 2 mg/day and 100 mg/day, respectively, without any reemergence of the symptoms of cryoglobulinemia or relapse of the nephrotic syndrome for three years. Here, we report this case with essential mixed cryoglobulinemia in whom we could achieve complete remission of the disease by adding cryofiltration to the oral corticosteroid and immunosuppressant therapy with mizoribine and could maintain for a long time.


Subject(s)
Blood Component Removal , Cryoglobulinemia/complications , Glomerulonephritis, Membranoproliferative/therapy , Immunosuppressive Agents/therapeutic use , Ribonucleosides/therapeutic use , Aged , Glomerulonephritis, Membranoproliferative/etiology , Glomerulonephritis, Membranoproliferative/pathology , Glucocorticoids/therapeutic use , Humans , Kidney/pathology , Male , Prednisolone/therapeutic use
13.
Anal Sci ; 34(4): 495-500, 2018.
Article in English | MEDLINE | ID: mdl-29643314

ABSTRACT

Monitoring of trace water in industrial gases is strongly recommended because contaminants cause serious problems during use, especially in the semiconductor industry. An ultra-sensitive trace-water sensor was developed with an in situ-synthesized metal-organic framework as the sensing material. The sample gas is passed through the sensing membrane and efficiently and rapidly collected by the sensing material in the newly designed gas collection/detection cell. The sensing membrane, glass paper impregnated with copper 1,3,5-benzenetricarboxylate (Cu-BTC), is also newly developed. The amount and density of the sensing material in the sensing membrane must be well balanced to achieve rapid and sensitive responses. In the present study, Cu-BTC was synthesized in situ in glass paper. The developed system gave high sensing performances with a limit of detection (signal/noise ratio = 3) of 9 parts per billion by volume (ppbv) H2O and a 90% response time of 86 s for 200 ppbv H2O. The reproducibility of the responses within and between lots had relative standard deviations for 500 ppbv H2O of 0.8% (n = 10) and 1.5% (n = 3), respectively. The long-term (2 weeks) stability was 7.3% for 400 ppbv H2O and one-year continuous monitoring test showed the sensitivity change of <∼3% before and after the study. Furthermore, the system response was in good agreement with the response achieved in cavity ring-down spectroscopy. These performances are sufficient for monitoring trace water in industrial gases. The integrated system with light and gas transparent structure for gas collection/absorbance detection can also be used for other target gases, using specific metal-organic frameworks.

14.
Clin Exp Nephrol ; 22(1): 35-44, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28421299

ABSTRACT

BACKGROUND: Hyperkalemia is prevalent in end-stage renal disease patients, being involved in life-threatening arrhythmias. Although polystyrene sulfonate (PS) is commonly used for the treatment of hyperkalemia, direct comparison of effects between calcium and sodium PS (CPS and SPS) on mineral and bone metabolism has not yet been studied. METHODS: In a randomized and crossover design, 20 pre-dialysis patients with hyperkalemia (>5 mmol/l) received either oral CPS or SPS therapy for 4 weeks. RESULTS: After 4-week treatments, there was no significant difference of changes in serum potassium (K) from the baseline (ΔK) between the two groups. However, SPS significantly decreased serum calcium (Ca) and magnesium (Mg) and increased intact parathyroid hormone (iPTH) values, whereas CPS reduced iPTH. ΔiPTH was inversely correlated with ΔCa and ΔMg (r = -0.53 and r = -0.50, respectively). Furthermore, sodium (Na) and atrial natriuretic peptide (ANP) levels were significantly elevated in patients with SPS, but not with CPS, whereas ΔNa and ΔANP were significantly correlated with each other in all the patients. We also found that ΔNa and Δ(Na to chloride ratio) were positively correlated with ΔHCO3-. In artificial colon fluid, CPS increased Ca and decreased Na. Furthermore, SPS greatly reduced K, Mg, and NH3. CONCLUSION: Compared with SPS, CPS may be safer for the treatment of hyperkalemia in pre-dialysis patients, because it did not induce hyperparathyroidism or volume overload.


Subject(s)
Bone and Bones/metabolism , Calcium/therapeutic use , Hyperkalemia/drug therapy , Minerals/metabolism , Polystyrenes/therapeutic use , Aged , Aged, 80 and over , Bone and Bones/drug effects , Calcium/blood , Cross-Over Studies , Female , Humans , Hyperkalemia/blood , Hyperkalemia/metabolism , Magnesium/blood , Male , Middle Aged , Parathyroid Hormone/blood , Prospective Studies , Renal Dialysis , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/metabolism , Sodium/blood
15.
CEN Case Rep ; 7(1): 48-54, 2018 May.
Article in English | MEDLINE | ID: mdl-29181824

ABSTRACT

We report a case of smoking-related idiopathic nodular glomerulosclerosis (ING) with overexpression of glomerular advanced glycation end products (AGEs) and their receptor (RAGE). A 59-year-old Japanese man with nephrotic syndrome, who had a smoking history of one pack of cigarettes per day for approximately 40 years, presented with a 3-year history of urinalysis abnormalities without clinical evidence of diabetic mellitus. The patient's leg edema progressively worsened over the previous 2 years, and he was admitted to our hospital. Renal biopsy showed mesangial expansion with diabetic Kimmelstiel-Wilson-like nodular lesions, glomerular basement thickening, and arteriosclerosis. No electron-dense deposits, fibrils, or microtubule deposits were seen in the glomeruli on electron microscopy. Skin AGE level measured using AGE reader was higher in this case than the average level in age-matched Caucasians. In addition, immunohistochemical analysis revealed that N-carboxymethyl lysine, one of the major AGEs, and RAGE were overexpressed and podocin expression was decreased in the peripheral area of the glomerular nodular lesions. These observations suggest that AGEs-RAGE system may be activated in smoking-related ING, possibly leading to the progression of renal dysfunction.

16.
PLoS One ; 12(12): e0190095, 2017.
Article in English | MEDLINE | ID: mdl-29267354

ABSTRACT

Mucosal barrier formed by cationic antimicrobial peptides (CAMPs) is believed to be crucial for host protection from pathogenic gut infection. However, some pathogens can develop resistance to the CAMPs to survive in hosts. Salmonella enterica is a common cause of acute diarrhea. During the course of this disease, the pathogen must continuously colonize the gut lumen, which contains CAMPs. However, it is incompletely understood whether the resistance of Salmonella strains to CAMPs contributes to the development of gut infections. PhoPQ two-component system-dependent lipid A modifications confer resistance to CAMPs in S. enterica serovar Typhimurium. Therefore, we introduced mutations into the PhoPQ-regulated genes in an S. Typhimurium strain, obtaining pagP ugtL and pmrA mutant strains. Each mutant strain demonstrated a distinct spectrum of the resistance to CAMPs. Using streptomycin mouse model for Salmonella diarrhea, we show that the pagP ugtL, but not pmrA, mutant strain had a gut colonization defect. Furthermore, the pagP ugtL, but not pmrA, mutant strain had decreased outer membrane integrity and susceptibility to magainin 2, an alpha-helical CAMP. Taken together, the PagP- and UgtL-dependent resistance to CAMPs was demonstrated to contribute to sustained colonization in the gut. This may be due to the robust outer membrane of S. Typhimurium, inducing the resistance to alpha-helical CAMPs such as α-defensins. Our findings indicate that the development of resistance to CAMPs is required for the S. Typhimurium gut infection.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Proteins/metabolism , Intestines/microbiology , Peptides/pharmacology , Salmonella typhimurium/drug effects , Salmonella typhimurium/metabolism
17.
Anal Chim Acta ; 886: 188-93, 2015 Jul 30.
Article in English | MEDLINE | ID: mdl-26320652

ABSTRACT

Industrial gases such as nitrogen, oxygen, argon, and helium are easily contaminated with water during production, transfer and use, because there is a high volume fraction of water in the atmosphere (approximately 1.2% estimated with the average annual atmospheric temperature and relative humidity). Even trace water (<1 parts per million by volume (ppmv) of H2O, dew point < -76 °C) in the industrial gases can cause quality problems in the process such as production of semiconductors. Therefore, it is important to monitor and to control trace water levels in industrial gases at each supplying step, and especially during their use. In the present study, a fiber optic gas sensor was investigated for monitoring trace water levels in industrial gases. The sensor consists of a film containing a metal organic framework (MOF). MOFs are made of metals coordinated to organic ligands, and have mesoscale pores that adsorb gas molecules. When the MOF, copper benzene-1,3,5-tricarboxylate (Cu-BTC), was used as a sensing material, we investigated the color of Cu-BTC with water adsorption changed both in depth and tone. Cu-BTC crystals appeared deep blue in dry gases, and then changed to light blue in wet gases. An optical gas sensor with the Cu-BTC film was developed using a light emitting diode as the light source and a photodiode as the light intensity detector. The sensor showed a reversible response to trace water, did not require heating to remove the adsorbed water molecules. The sample gas flow rate did not affect the sensitivity. The obtained limit of detection was 40 parts per billion by volume (ppbv). The response time for sample gas containing 2.5 ppmvH2O was 23 s. The standard deviation obtained for daily analysis of 1.0 ppmvH2O standard gas over 20 days was 9%. Furthermore, the type of industrial gas did not affect the sensitivity. These properties mean the sensor will be applicable to trace water detection in various industrial gases.

18.
Dev Growth Differ ; 49(7): 623-34, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17716306

ABSTRACT

Translational regulation has been to shown to play major roles in the patterning of the early Drosophila embryo. The eIF4G family member NAT1/p97/DAP5 has been identified as a novel translational repressor. To genetically dissect the in vivo function of this unconventional eIF4G-related translational regulator, Drosophila NAT1 (dNAT1) mutants were isolated using a reverse-genetics approach. Four transposon insertion mutants and a deletion mutant affecting the dNAT1 locus were analyzed. Genetic complementation tests and germline rescue using a 12 kb dNAT1 genomic DNA fragment revealed these to be loss-of-function mutants. One P-element insertion line, dNAT1(GS1.), shows severe embryonic lethality and abnormal germband extension. Abnormalities at metamorphosis were also found, including defective head eversion and salivary gland degeneration in the hypomorphic allele dNAT(ex1). A phenotypic analysis of dNAT1 mutants suggests that dNAT protein plays a specific rather than general role in translational regulation.


Subject(s)
Drosophila Proteins/genetics , Drosophila/embryology , Embryonic Development , Eukaryotic Initiation Factor-4G/genetics , Germ Cells , Metamorphosis, Biological/genetics , Amino Acid Sequence , Animals , Base Sequence , DNA Primers , In Situ Hybridization , Mutation , Protein Biosynthesis , Sequence Homology, Amino Acid , Sequence Homology, Nucleic Acid
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