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1.
Front Plant Sci ; 15: 1371123, 2024.
Article in English | MEDLINE | ID: mdl-38721332

ABSTRACT

We aimed to evaluate the facilitation effects of an aluminum (Al) hyperaccumulator species bearing cluster roots, Gevuina avellana, on the seedling growth and performance of an Al-intolerant and phosphorus (P)-deficient-sensitive plant, Vaccinium corymbosum. For this, seedlings of G. avellana and V. corymbosum were grown alone or together as follows: i) two G. avellana seedlings, ii) one G. avellana + one V. corymbosum and iii) two V. corymbosum, in soil supplemented with Al (as Al2(SO4)3) and in the control (without Al supplementation). We determined relative growth rate (RGR), photosynthetic rate, chlorophyll concentration, lipid peroxidation and Al and nutrient concentration [Nitrogen (N), P, potassium (K), calcium (Ca), magnesium (Mg), sodium (Na), manganese (Mn), iron (Fe), copper (Cu), zinc (Zn), and sulfur (S)] in leaves and roots of both species. The results showed that, in general, G. avellana did not assist V. corymbosum to enhance its RGR nor reduce its Al uptake. However, G. avellana assisted V. corymbosum in enhanced N acquisition and, consequently, to increase its chlorophyll concentration and photosynthetic rate. Besides, V. corymbosum had lower lipid peroxidation in leaves when grown in the soil with high Al supplementation in association with G. avellana. Our results suggest a facilitating effect of G. avellana to V. corymbosum when grown in soils with high Al concentration, by enhancing chlorophyll concentrations and photosynthetic rate, and decreasing the oxidative damage to lipids.

2.
J Gambl Stud ; 39(1): 103-117, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36152112

ABSTRACT

As real time soccer gambling is becoming a game of choice for many Nigerian youths, there is need to examine some predictive factors that could account for risky decision making in the population. We combined some cognitive tasks (memory, concentration, executive function and problem solving) and non-cognitive measures (time taken to complete a bet, years of gambling and addiction tendency measures) to derive a more parsimonious model of predicting risky decision making in this population. Twenty-eight undergraduate students that endorsed regular involvement (at least once a week) in soccer betting and were willing to come to the psychology lab for testing were recruited. Four neuropsychological measures (Craft Story 21: Immediate and delayed, Number Span Test: Forward and backward, Trail Making Test: A&B, Tower of Hannoi and a gambling questionnaire (Gamblers Anonymous Questionnaire) were used for the study. Study design was correlational and linear regression (step wise method) was used for data analysis. Step wise regression statistics yielded nine possible model combinations with high predictive strengths. Overall, model 9 (with adjusted R2 = 0.57) that has 6 measures including one from non-cognitive and 5 from cognitive measures was adjudged to be most parsimonious putting into consideration its predictive strength and number of tasks required. The tasks in our most parsimonious model were: time taken to complete a bet (non-cognitive), Craft Story 21: immediate (cognitive: memory), Number Span Forward: Total correct and longest correct (cognitive: concentration), Trail Making Test: B (cognitive: executive function) and Tower of Hannoi: Time taken to complete (cognitive: problem solving). Pearson product moment correlation between the predictor variables and the dependent variable (number of odds selected) showed inverse correlation of Craft Story Immediate, Number Span total correct and Number span longest correct suggesting strong divergence of these variables to odd selection. Time taken to complete bet, Trail Making Test: B and time taken to complete Tower of Hannoi respectively had positive correlations with number of odds selected. Our results suggest that multiple domains of cognitive abilities and time taken to complete a bet are important for predicting gamblers at risk for poor decision making. It further suggests that use of single task for a particular cognitive domain could be sufficient in predicting persons at risk for decision making. Overall, our study suggests that risky decision making in real time sports betting could be predicted using fewer neuropsychological tasks measuring wider domains of brain behaviour and a non-cognitive measure.


Subject(s)
Gambling , Soccer , Adolescent , Humans , Gambling/psychology , Nigeria , Cognition , Decision Making , Neuropsychological Tests
3.
Blood Rev ; 56: 100983, 2022 11.
Article in English | MEDLINE | ID: mdl-35750558

ABSTRACT

Sickle cell disease is a very variable condition, with outcomes ranging from death in childhood to living relatively symptom free into the 8th decade. Much of this variability is unexplained. The co-inheritance of α thalassaemia and factors determining HbF levels significantly modify the phenotype, but few other significant genetic variants have been identified, despite extensive studies. Environmental factors are undoubtedly important, with socio-economics and access to basic medical care explaining the huge differences in outcomes between many low- and high-income countries. Exposure to cold and windy weather seems to precipitate acute complications in many people, although these effects are unpredictable and vary with geography. Many studies have tried to identify prognostic factors which can be used to predict outcomes, particularly when applied in infancy. Overall, low haemoglobin, low haemoglobin F percentage and high reticulocytes in childhood are associated with worse outcomes, although again these effects are fairly weak and inconsistent.


Subject(s)
Anemia, Sickle Cell , Fetal Hemoglobin , Humans , Fetal Hemoglobin/genetics , Anemia, Sickle Cell/complications , Anemia, Sickle Cell/diagnosis , Anemia, Sickle Cell/epidemiology , Reticulocytes
4.
Front Immunol ; 12: 650841, 2021.
Article in English | MEDLINE | ID: mdl-33777049

ABSTRACT

Dendritic cells (DCs) have the ability to stimulate naïve T cells that coordinate subsequent adaptive response toward an inflammatory response or tolerance depending on the DC differentiation level. Inotodiol, a lanostane triterpenoid found in Inonotus obliquus (wild Chaga mushroom), is a natural compound with a wide range of biological activities. In this study, we investigated whether inotodiol promotes the maturation of bone marrow-derived DCs (BMDCs) and inotodiol-treated BMDCs induce T cell activation. Inotodiol increased the expression of surface maturation markers, including MHC-I, MHC-II, CD86, and CD40, on BMDCs without affecting the production of various cytokines, including TNF-α and IL-12p40 in these cells. T cells primed with inotodiol-treated BMDCs proliferated and produced IL-2, without producing other cytokines, including IL-12p40 and IFN-γ. Injection of inotodiol into mice induced maturation of splenic DCs and IL-2 production, and the administration of inotodiol and inotodiol-treated BMDCs induced the proliferation of adoptively transferred CD8+ T cells in vivo. The phosphatidylinositol-3-kinase inhibitor wortmannin abrogated the upregulation of Akt phosphorylation and CD86 and MHC-II expression induced by inotodiol. However, inotodiol failed to induce phosphorylation of the IκB kinase and degradation of IκB-α, and increased expression of CD86 induced by inotodiol was not blocked by an IκB kinase inhibitor. These results suggest that inotodiol induces a characteristic type of maturation in DCs through phosphatidylinositol-3-kinase activation independent of NF-κB, and inotodiol-treated DCs enhance T cell proliferation and IL-2 secretion.


Subject(s)
Agaricales/chemistry , Bone Marrow Cells/drug effects , Cell Differentiation/drug effects , Dendritic Cells/drug effects , Inonotus/chemistry , Lanosterol/analogs & derivatives , Animals , Bone Marrow Cells/immunology , Bone Marrow Cells/metabolism , CD8-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , Cell Differentiation/immunology , Cell Proliferation/drug effects , Cells, Cultured , Cytokines/immunology , Cytokines/metabolism , Dendritic Cells/immunology , Dendritic Cells/metabolism , Lanosterol/chemistry , Lanosterol/pharmacology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Molecular Structure , Phosphorylation/drug effects , Proto-Oncogene Proteins c-akt/immunology , Proto-Oncogene Proteins c-akt/metabolism , RAW 264.7 Cells
5.
Indian J Nephrol ; 31(6): 555-558, 2021.
Article in English | MEDLINE | ID: mdl-35068763

ABSTRACT

Delayed interferon secretion and cytokine dysregulation are responsible for the life-threatening acute respiratory distress syndrome (ARDS), multiorgan dysfunction and shock in COVID 19, which closely resembles secondary hemophagocytic lymphohistiocytosis (sHLH). IL-6, a marker of hypercytokinemia in patients with COVID-19 is positively correlated with disease severity, development and progression of ARDS, and mortality. Therapy to either reduce IL-6 or inhibit its action with either non-specific inhibitors of inflammation like dexamthasone or Toclizumab a specific inhibitor of IL-6 has produced decrease in mortality. We describe a novel method of treatment in a patient with multiorgan involvement in COVID 19, using the oXiris hemofilter which delivers renal replacement therapy while also reducing cytokines like IL-6.

6.
Indian J Crit Care Med ; 24(8): 624-625, 2020 Aug.
Article in English | MEDLINE | ID: mdl-33024364

ABSTRACT

Recent trials have failed to show a survival benefit from the early initiation of dialytic therapies in acute kidney injury (AKI), but the problem has not been studied in pregnancy-related AKI. While the KDIGO criteria have not been validated in pregnancy-related acute kidney injury (PRAKI), additionally both fetal and maternal outcomes require to be studied. The short observational study by Banerjee et al. contains some interesting observations. HOW TO CITE THIS ARTICLE: Lobo VA. Renal Replacement Therapy in Pregnancy-related Acute Kidney Injury: Getting the Timing Right. Indian J Crit Care Med 2020;24(8):624-625.

7.
Indian J Crit Care Med ; 24(Suppl 3): S102-S106, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32704214

ABSTRACT

Renal replacement therapy (RRT) for acute kidney injury (AKI) patients in an intensive care unit (ICU) presents unique problems of providing biochemical and fluid removal in patients with unstable circulations, inotropes, and increased capillary permeability. Although no individual modality has been shown to confer a mortality benefit, it is assumed that continuous therapies like peritoneal dialysis (PD) and venovenous hemofiltration or hemodiafiltration may be better tolerated by the patient with hemodynamic instability, raised intracranial pressure (ICP), and liver failure. An individual patient may require more than one treatment in the course of his/her illness. The therapies offered may reflect available resources, local expertise, and cost constraints. HOW TO CITE THIS ARTICLE: Lobo VA. Renal Replacement Therapy in Acute Kidney Injury: Which Mode and When? Indian J Crit Care Med 2020;24(Suppl 3):S102-S106.

8.
Hemodial Int ; 23(4): E106-E110, 2019 10.
Article in English | MEDLINE | ID: mdl-31115142

ABSTRACT

As maintenance hemodialysis patients are exposed to large quantities of dialysis water, any contamination of it might be reflected in plasma levels. We present a series of cases due to such a contamination. Six maintenance hemodialysis patients dialyzing at the same peripheral hemodialysis facility presented to us over a short period of time with symptoms mimicking inadequate dialysis. Their blood urea and creatinine levels were not very high, but all the patients had hypermagnesemia [serum Mg levels = 1.8 (±0.3) mmol/L]. Except for one patient who had cardiac arrest at presentation, all patients improved after undergoing hemodialysis at our center [serum Mg at discharge = 0.86 (±0.01) mmol/L]. The origin of hypermagnesemia was traced to dialysis water contamination with magnesium due to inadequate maintenance of the water treatment system. Corrective measures improved the quality of water, and no further cases were reported from that center. Proper maintenance and periodic checks of the quality of water are central to the outcomes of maintenance hemodialysis patients.


Subject(s)
Dialysis Solutions/adverse effects , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Magnesium/adverse effects , Muscle Weakness/chemically induced , Nausea/chemically induced , Renal Dialysis/adverse effects , Humans , Magnesium/blood , Male , Middle Aged , Renal Dialysis/methods
9.
Opt Lett ; 43(1): 26-29, 2018 Jan 01.
Article in English | MEDLINE | ID: mdl-29328188

ABSTRACT

This Letter shows the features of inverse Faraday effect (IFE) in a graphene-dielectric-metal (GDM) structure. The constants of propagation and attenuation of the surface plasmon-polariton modes are calculated. The effective magnetic field induced by surface plasmon modes in the dielectric due to the IFE is estimated to reach above 1 tesla. The possibility to control the distribution of the magnetic field by chemical potential of graphene is shown. The concept of strain-driven control of the IFE in the structure has been proposed and investigated.

10.
Nanoscale ; 9(35): 13069-13078, 2017 Sep 14.
Article in English | MEDLINE | ID: mdl-28837196

ABSTRACT

We have demonstrated for the first time an inkjet fabrication of highly efficient luminescent structures based on Eu-doped ZrO2 nanocrystals (3.4 ± 0.3 nm), with a refractive index close to the one of the bulk materials. The nanoparticles were synthesised using a nonhydrolytic method in benzyl alcohol where the particles were post treated using acetic acid, leading to the formation of a stable colloid. It was shown that the non-polar methyl group of the acetic acid is responsible for its penetration through the hydrophobic layer all the way through to the surface of the ZrO2, leading to the cleavage of the Zr-OCH2C6H5 bond and the formation of surface acetate species and a concomitant decomposition of the zirconia superlattice. Hereby we show a new and efficient universal ink production through a multi-step process - starting from solvothermal synthesis, dispersion of nanocrystals in water, and adaptation of the rheological parameters of the resulting sols. Eventually, we were able to obtain inks that we used for the production of optical coatings, monolayer luminescent-protected holography and anti-counterfeiting printing. These structures, obtained at room temperature through inkjet printing, present dense xerogel structures with high optical transparency, a high refractive index and more efficient luminescence compared with the non-homogeneous structures produced as a mixture of rare-earth elements and nanocrystals.

11.
Plant Biol (Stuttg) ; 19(5): 742-748, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28667797

ABSTRACT

Shrubby legumes in Mediterranean-type ecosystems face strong nutrient limitations that worsen in summer, when water is absent. Nitrogen-fixing legumes are likely to be able to switch between soil N and atmospheric N (N2 ) sources to adjust the C costs of N acquisition in different seasons. We investigated the utilisation of different inorganic N sources by two indigenous shrubby legumes (Cytisus multiflorus and Cytisus scoparius). Plant performance in terms of photosynthesis and biomass production was also analysed. Plants were cultivated in sterile river sand supplied with Hoagland nutrient solution, grown in N-free nutrient solution and inoculated with effective rhizobial strains from nodules of adult plants of the same species. A second treatment consisted of plants given 500 µm NH4 NO3 added into the nutrient solution. In a third treatment, plants were watered with another source of N (500 µm NH4 NO3 ) as well as being inoculated with effective rhizobial strains. The application of NH4 NO3 to the legumes resulted in a larger increase in plant dry matter. Carbon construction costs were higher in plants supplied with mineral and symbiotic N sources and always higher in the endemic C. multiflorus. Differences in photosynthesis rates were only observed between species, regardless of the N source. Non-fertilised inoculated plants had more effective root nodules and a clear dependence on N2 fixation. We propose that the ability of C. scoparius to change N source makes it a plastic species, which would account for its broader distribution in nature.


Subject(s)
Cytisus/metabolism , Nitrogen/metabolism , Fabaceae/metabolism , Nitrogen Fixation , Root Nodules, Plant/metabolism
12.
ACS Appl Mater Interfaces ; 9(8): 7044-7049, 2017 Mar 01.
Article in English | MEDLINE | ID: mdl-28177602

ABSTRACT

This paper presents the first experimental evidence of pronounced electrification effects upon reversible cycle of forced water intrusion-extrusion in nanoporous hydrophobic materials. Recorded generation of electricity combined with high-pressure calorimetric measurements improves the energy balance of {nanoporous solid + nonwetting liquid} systems by compensating mechanical and thermal energy hysteresis in the cycle. Revealed phenomena provide a novel way of "mechanical to electrical" and/or "thermal to electrical" energy transformation with unprecedented efficiency and additionally open a perspective to increase the efficiency of numerous energy applications based on such systems taking advantage of electricity generation during operational cycle.

13.
Cochrane Database Syst Rev ; 1: CD006415, 2017 01 23.
Article in English | MEDLINE | ID: mdl-28112384

ABSTRACT

BACKGROUND: Surgery remains an acceptable treatment modality for tubal infertility despite the rise in usage of in vitro fertilisation (IVF). Estimated livebirth rates after surgery range from 9% for women with severe tubal disease to 69% for those with mild disease; however, the effectiveness of surgery has not been rigorously evaluated in comparison with other treatments such as IVF and expectant management (no treatment). Livebirth rates have not been adequately assessed in relation to the severity of tubal damage. It is important to determine the effectiveness of surgery against other treatment options in women with tubal infertility because of concerns about adverse outcomes, intraoperative complications and costs associated with tubal surgery, as well as alternative treatments, mainly IVF. OBJECTIVES: The aim of this review was to determine the effectiveness and safety of surgery compared with expectant management or IVF in improving the probability of livebirth in the context of tubal infertility (regardless of grade of severity). SEARCH METHODS: We searched the following databases in October 2016: the Cochrane Gynaecology and Fertility (CGF) Group trials register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and PsycINFO; as well as clinical trials registries, sources of unpublished literature and reference lists of included trials and related systematic reviews. SELECTION CRITERIA: We considered only randomised controlled trials to be eligible for inclusion, with livebirth rate per participant as the primary outcome of interest. DATA COLLECTION AND ANALYSIS: We planned that two review authors would independently assess trial eligibility and risk of bias and would extract study data. The primary review outcome was cumulative livebirth rate. Pregnancy rate and adverse outcomes, including miscarriage rate, rate of ectopic pregnancy and rate of procedure-related complications, were secondary outcomes. We planned to combine data to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). We planned to assess statistical heterogeneity using the I2 statistic and to assess the overall quality of evidence for the main comparisons using GRADE methods. MAIN RESULTS: We identified no suitable randomised controlled trials. AUTHORS' CONCLUSIONS: The effectiveness of tubal surgery relative to expectant management and IVF in terms of livebirth rates for women with tubal infertility remains unknown. Large trials with adequate power are warranted to establish the effectiveness of surgery in these women. Future trials should not only report livebirth rates per patient but should compare adverse effects and costs of treatment over a longer time. Factors that have a major effect on these outcomes, such as fertility treatment, female partner's age, duration of infertility and previous pregnancy history, should be considered. Researchers should report livebirth rates in relation to severity of tubal damage and different techniques used for tubal repair, including microsurgery and laparoscopic methods.


Subject(s)
Fallopian Tube Diseases/surgery , Fallopian Tubes/surgery , Infertility, Female/surgery , Female , Fertilization in Vitro , Humans , Watchful Waiting
15.
Child Care Health Dev ; 42(4): 521-33, 2016 07.
Article in English | MEDLINE | ID: mdl-27272608

ABSTRACT

BACKGROUND: National Institute for Health and Care Excellence guidelines recommend a stepped care approach for the identification and management of children with, or at risk of, attention-deficit/hyperactivity disorder (ADHD). We investigated the effectiveness, cost-effectiveness and acceptability of a group parenting intervention programme (+/- a teacher session) for children at risk of ADHD. METHODS: In a three-arm cluster randomised controlled trial, 12 primary schools were randomly assigned to control, parent-only and combined (parent + teacher) intervention arms. Eligible children had high levels of parent-rated hyperactivity/inattention (n = 199). At 6 month follow-up, the primary outcome measure was the parent-completed Conners' Rating Scale - Revised (ADHD index). Secondary outcomes included the Conners' sub-scales (hyperactivity, cognitive problems/inattention and oppositional behaviour), the teacher-completed Conners' Rating Scale - Revised, child health-related quality of life, parental burden and parental mental health. The cost-effectiveness analyses reflected a health and personal social services perspective. TRIAL REGISTRATION: ISRCTN87634685. RESULTS: Follow-up data were obtained from 76 parents and 169 teachers. There was no effect of the parent-only (mean difference = -1.1, 95% CI -5.1,2.9; p = 0.57) or combined interventions (mean difference = -2.1, 95% CI -6.4,2.1; p = 0.31) on the ADHD index. The combined intervention was associated with reduced parent-reported hyperactivity symptoms (mean difference = -5.3; 95% CI -10.5,-0.01; p = 0.05) and the parent-only intervention with improved parental mental health (mean difference = -1.9; 95% CI -3.2,-0.5; p = 0.009). The incremental costs of the parent-only and the combined interventions were £73 and £123, respectively. Above a willingness-to-pay of £31 per one-point improvement in the ADHD index, the parent-only programme had the highest probability of cost-effectiveness. Participants found the interventions acceptable. CONCLUSIONS: For children at risk of ADHD, this school-based parenting programme was not associated with improvement in core ADHD symptoms. Secondary analyses suggested a possible reduction in parent-reported hyperactivity and parental mental health problems. Future research should compare targeted interventions against watchful waiting and specialist referral.


Subject(s)
Attention Deficit Disorder with Hyperactivity/diagnosis , Cost-Benefit Analysis , Health Services Research , Referral and Consultation/organization & administration , School Health Services , Attention Deficit Disorder with Hyperactivity/epidemiology , Child , Female , Health Services Research/economics , Humans , Male , Parents , Practice Guidelines as Topic , Program Evaluation , Referral and Consultation/economics , Risk Assessment , School Health Services/economics , School Health Services/organization & administration , United Kingdom/epidemiology , Watchful Waiting/economics
17.
Int J Obstet Anesth ; 24(3): 210-6, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25936786

ABSTRACT

BACKGROUND: Combination opioid-acetaminophen drugs are commonly used for pain management after cesarean delivery. The aim of this study was to determine if scheduled acetaminophen decreases opioid use compared to as-needed combination acetaminophen-opioid administration. METHODS: We performed a retrospective chart review of women who underwent cesarean delivery before and after a clinical practice change. All patients received spinal anesthesia containing intrathecal morphine 200µg and scheduled non-steroidal anti-inflammatory drugs for 48h postoperatively. The first group (As-Needed Group, n=120) received combination oral opioid-acetaminophen analgesics as needed for breakthrough pain. The second group (Scheduled Group, n=120) received oral acetaminophen 650mg every 6h for 48h postoperatively with oral oxycodone administered as needed for breakthrough pain. The primary outcome was opioid use, measured in intravenous morphine mg equivalents, in the first 48h postoperatively. RESULTS: The Scheduled Group used 9.1±2.1mg (95% CI 5.0-13.2) fewer intravenous morphine equivalents than the As-Needed Group (P <0.0001) over the study period. Fewer patients in the Scheduled Group exceeded acetaminophen 3g daily compared to the As-Needed Group (P=0.008). Pain scores were similar between study groups. CONCLUSIONS: After cesarean delivery, scheduled acetaminophen results in decreased opioid use and more consistent acetaminophen intake compared to acetaminophen administered as needed via combination acetaminophen-opioid analgesics, without compromising analgesia.


Subject(s)
Acetaminophen/administration & dosage , Analgesics, Non-Narcotic/administration & dosage , Analgesics, Opioid/administration & dosage , Cesarean Section , Pain, Postoperative/drug therapy , Adult , Female , Humans , Morphine/administration & dosage , Pregnancy , Retrospective Studies
18.
Anal Chem ; 86(8): 3693-6, 2014 Apr 15.
Article in English | MEDLINE | ID: mdl-24625060

ABSTRACT

Simple, fast, and theoretically substantiated experimental method for determination of improved selectivity coefficients is proposed. The method is based on the well-known fact that low selectivity coefficients determined by the separate solution method (SSM) are time-dependent and, upon our finding, this dependence is a well-defined linear function of time raised to the certain negative power. In particular, the selectivity coefficients obtained for equally charged primary and foreign ions by SSM linearly depend on time to the minus one-fourth. It was found that extrapolation of experimental data using this function to the intersection with Y axes gives reliable values of rather low selectivity coefficients (down to n × 10(-7)), which strongly differ from those measured using SSM and correspond well with the values obtained using the modified separate solution method (MSSM) proposed by Bakker. At the same time, the new method is free of one very essential limitation inherent to MSSM, namely, it is applicable after the conditioning of electrodes in the primary ion solution and can be repeated many times.

19.
Oncogene ; 33(26): 3441-50, 2014 Jun 26.
Article in English | MEDLINE | ID: mdl-23912458

ABSTRACT

FKBPL has been implicated in processes associated with cancer, including regulation of tumor growth and angiogenesis with high levels of FKBPL prognosticating for improved patient survival. Understanding how FKBPL levels are controlled within the cell is therefore critical. We have identified a novel role for RBCK1 as an FKBPL-interacting protein, which regulates FKBPL stability at the post-translational level via ubiquitination. Both RBCK1 and FKBPL are upregulated by 17-ß-estradiol and interact within heat shock protein 90 chaperone complexes, together with estrogen receptor-α (ERα). Furthermore, FKBPL and RBCK1 associate with ERα at the promoter of the estrogen responsive gene, pS2, and regulate pS2 levels. MCF-7 clones stably overexpressing RBCK1 were shown to have reduced proliferation and increased levels of FKBPL and p21. Furthermore, these clones were resistant to tamoxifen therapy, suggesting that RBCK1 could be a predictive marker of response to endocrine therapy. RBCK1 knockdown using targeted small interfering RNA resulted in increased proliferation and increased sensitivity to tamoxifen treatment. Moreover, in support of our in vitro data, analysis of mRNA microarray data sets demonstrated that high levels of FKBPL and RBCK1 correlated with increased patient survival, whereas high RBCK1 predicted for a poor response to tamoxifen. Our findings support a role for RBCK1 in the regulation of FKBPL with important implications for estrogen receptor signaling, cell proliferation and response to endocrine therapy.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Cyclin-Dependent Kinase Inhibitor p21/biosynthesis , Drug Resistance, Neoplasm/genetics , Immunophilins/genetics , Tamoxifen/therapeutic use , Transcription Factors/genetics , Animals , Antineoplastic Agents, Hormonal/pharmacology , Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Breast Neoplasms/mortality , COS Cells , Cell Line, Tumor , Cell Proliferation , Chlorocebus aethiops , Estradiol/metabolism , Female , Gene Expression Regulation, Neoplastic , HSP90 Heat-Shock Proteins/genetics , HSP90 Heat-Shock Proteins/metabolism , Humans , Immunophilins/biosynthesis , Neovascularization, Pathologic/genetics , Promoter Regions, Genetic/genetics , RNA Interference , RNA, Small Interfering , Receptors, Estrogen/genetics , Signal Transduction/genetics , Tacrolimus Binding Proteins , Tamoxifen/pharmacology , Transcription Factors/biosynthesis , Transcriptional Activation , Treatment Outcome , Trefoil Factor-1 , Tumor Suppressor Proteins/biosynthesis , Tumor Suppressor Proteins/genetics , Ubiquitin-Protein Ligases , Ubiquitination
20.
J Feline Med Surg ; 16(4): 378-80, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24027050

ABSTRACT

Two male neutered domestic shorthair cats were evaluated for generalised tremors. On neurological examination both cats showed whole-body tremors, worsening with stress. A mainly cerebellar disorder was suspected. Blood examination, cerebrospinal fluid analysis and electrophysiological examination of both cats and magnetic resonance imaging of the brain in one cat were normal. Idiopathic generalised tremor syndrome (IGTS) was suspected owing to the exclusion of underlying causes and the clinical similarities with the syndrome in dogs. Treatment as recommended for dogs was initiated and resulted in improvement. This report describes the first cases of IGTS in cats.


Subject(s)
Cat Diseases/diagnosis , Cerebellar Diseases/veterinary , Tremor/veterinary , Animals , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/therapeutic use , Anticonvulsants/administration & dosage , Anticonvulsants/therapeutic use , Brain/anatomy & histology , Brain/physiology , Cat Diseases/drug therapy , Cats , Cerebellar Diseases/diagnosis , Cerebellar Diseases/pathology , Diazepam/administration & dosage , Diazepam/therapeutic use , Electroencephalography/veterinary , Magnetic Resonance Imaging/veterinary , Male , Prednisolone/administration & dosage , Prednisolone/therapeutic use , Tremor/diagnosis , Tremor/pathology
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