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1.
Neth Heart J ; 31(3): 117-123, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36445615

ABSTRACT

INTRODUCTION: In a Dutch heart centre, a dedicated chronic total occlusion (CTO) team was implemented in June 2017. The aim of this study was to the evaluate treatment success and clinical outcomes before and after this implementation. METHODS: A total of 662 patients who underwent percutaneous coronary intervention (PCI) for a CTO between January 2013 and June 2020 were included and divided into pre- and post-CTO team groups. The primary endpoint was the angiographic success rate of CTO-PCI. Secondary endpoints included angiographic success stratified by complexity using the J­CTO score and the following clinical outcomes: in-hospital complications and myocardial infarction, target vessel revascularisation, all-cause mortality, quality of life (QoL) and major adverse cardiac events (MACE) at 30-day and 1­year follow-up. RESULTS: Compared with the pre-CTO team group, the success rate in the post-CTO team group was higher after the first attempt (81.4% vs 62.7%; p < 0.001) and final attempt (86.7% vs 73.8%; p = 0.001). This was mainly driven by higher success rates for difficult and very difficult CTO lesions according to the J­CTO score. The MACE rate at 1 year was lower in the post-CTO team group than in the pre-CTO team group (6.4% vs 16.0%; p < 0.01), while it was comparable at 30-day follow-up (0.1% vs 1.7%; p = 0.74). Angina symptoms were significantly reduced at 30-day and 1­year follow-up, and QoL scores were higher after 1 year. CONCLUSION: This study demonstrated higher success rates of CTO-PCI and improved clinical outcomes and QoL at 1­year follow-up after implementation of a dedicated CTO team using the hybrid algorithm.

2.
Nat Commun ; 13(1): 6182, 2022 10 19.
Article in English | MEDLINE | ID: mdl-36261409

ABSTRACT

Ploidy changes are frequent in nature and contribute to evolution, functional specialization and tumorigenesis. Analysis of model organisms of different ploidies revealed that increased ploidy leads to an increase in cell and nuclear volume, reduced proliferation, metabolic changes, lower fitness, and increased genomic instability, but the underlying mechanisms remain poorly understood. To investigate how gene expression changes with cellular ploidy, we analyzed isogenic series of budding yeasts from 1N to 4N. We show that mRNA and protein abundance scales allometrically with ploidy, with tetraploid cells showing only threefold increase in protein abundance compared to haploids. This ploidy-dependent sublinear scaling occurs via decreased rRNA and ribosomal protein abundance and reduced translation. We demonstrate that the activity of Tor1 is reduced with increasing ploidy, which leads to diminished rRNA gene repression via a Tor1-Sch9-Tup1 signaling pathway. mTORC1 and S6K activity are also reduced in human tetraploid cells and the concomitant increase of the Tup1 homolog Tle1 downregulates the rDNA transcription. Our results suggest that the mTORC1-Sch9/S6K-Tup1/TLE1 pathway ensures proteome remodeling in response to increased ploidy.


Subject(s)
Proteome , Tetraploidy , Humans , Haploidy , Transcription Factors , RNA, Ribosomal , Ribosomal Proteins , DNA, Ribosomal/genetics , Mechanistic Target of Rapamycin Complex 1/genetics , RNA, Messenger
3.
Neth Heart J ; 29(4): 193-200, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33284420

ABSTRACT

OBJECTIVE: The aim of this study is to assess the effects on procedural, 30-day, and 1­year all-cause mortality by a newly introduced quality improvement strategy in patients after transcatheter aortic valve replacement (TAVR). METHODS: In October 2015, a coherent set of quality improving interventions with respect to patient geriatric screening, general diagnostic examination and safety of the procedure was implemented at a single centre in the Netherlands. Patients undergoing TAVR in 2013-2018 were included for retrospective analysis. Mortality was assessed in the pre-quality improvement strategy cohort (January 2013 to October 2015; cohort A) and in the post-quality improvement strategy cohort (November 2015 to December 2018; cohort B). Logistic regression analysis was used to estimate the influence of patient and procedural characteristics on the results of the quality improvement strategy in terms of procedural, 30-day, and 1­year all-cause mortality. RESULTS: In total, 806 patients were analysed with 274 patients in cohort A and 532 patients in cohort B. After introduction of the quality improvement strategy, procedural (4.4% to 1.3%, p < 0.01), 30-day (8.4% to 2.7%, p < 0.01) and 1­year (16.4% to 8.5%, p < 0.01) all-cause mortality significantly decreased. Multivariate regression analysis showed that the quality improvement strategy also significantly reduced 30-day (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.09-0.42) and 1­year (OR 0.38, 95% CI 0.24-0.61) all-cause mortality if corrected for patient characteristics. CONCLUSION: Structural meetings on evaluation of outcomes highlight potential areas for improvement and subsequent outcome-based quality improvement initiatives can result in lower procedural, 30-day, and 1­year all-cause mortality.

4.
Carcinogenesis ; 41(7): 984-992, 2020 07 14.
Article in English | MEDLINE | ID: mdl-31637423

ABSTRACT

Immunotherapy by blockade of the PD-1/PD-L1 checkpoint demonstrated amazing tumor response in advanced cancer patients including head and neck squamous cell carcinoma (HNSCC). However, the majority of HNSCC patients still show little improvement or even hyperprogression. Irradiation is currently investigated as synergistic treatment modality to immunotherapy as it increases the number of T-cells thereby enhancing efficacy of immunotherapy. Apart from this immunogenic context a growing amount of data indicates that PD-L1 also plays an intrinsic role in cancer cells by regulating different cellular functions like cell proliferation or migration. Here, we demonstrate opposing membrane localization of PD-L1 in vital and apoptotic cell populations of radioresistant (RR) and radiosensitive (RS) HNSCC cell lines up to 72 h after irradiation using flow cytometry. Moreover, strong PD-L1 expression was found in nuclear and cytoplasmic cell fractions of RR. After irradiation PD-L1 decreased in nuclear fractions and increased in cytoplasmic fractions of RR cells. In contrast, RS cell lines did not express PD-L1, neither in the nucleus nor in cytoplasmic fractions. Additionally, overexpression of PD-L1 in RS cells led to a proportional increase of vital PD-L1 positive cells after irradiation. Moreover, co-immunoprecipitation experiments revealed an interaction between Akt-1 and PD-L1, mostly in irradiated RR cells compared to RS cells suggesting a differential influence of PD-L1 on cell signaling. In summary, our data imply the need for different therapeutic strategies dependent on the molecular context in which PD-L1 is embedded.


Subject(s)
B7-H1 Antigen/genetics , Proto-Oncogene Proteins c-akt/genetics , Radiation Tolerance/genetics , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Apoptosis , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/immunology , Cell Line, Tumor , Cell Proliferation , Flow Cytometry , Gene Expression Regulation, Neoplastic/radiation effects , Humans , Immunotherapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/genetics , Programmed Cell Death 1 Receptor/immunology , Proto-Oncogene Proteins c-akt/immunology , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/immunology , Squamous Cell Carcinoma of Head and Neck/pathology , T-Lymphocytes/immunology
5.
Nat Plants ; 4(7): 473-484, 2018 07.
Article in English | MEDLINE | ID: mdl-29892093

ABSTRACT

Rose is the world's most important ornamental plant, with economic, cultural and symbolic value. Roses are cultivated worldwide and sold as garden roses, cut flowers and potted plants. Roses are outbred and can have various ploidy levels. Our objectives were to develop a high-quality reference genome sequence for the genus Rosa by sequencing a doubled haploid, combining long and short reads, and anchoring to a high-density genetic map, and to study the genome structure and genetic basis of major ornamental traits. We produced a doubled haploid rose line ('HapOB') from Rosa chinensis 'Old Blush' and generated a rose genome assembly anchored to seven pseudo-chromosomes (512 Mb with N50 of 3.4 Mb and 564 contigs). The length of 512 Mb represents 90.1-96.1% of the estimated haploid genome size of rose. Of the assembly, 95% is contained in only 196 contigs. The anchoring was validated using high-density diploid and tetraploid genetic maps. We delineated hallmark chromosomal features, including the pericentromeric regions, through annotation of transposable element families and positioned centromeric repeats using fluorescent in situ hybridization. The rose genome displays extensive synteny with the Fragaria vesca genome, and we delineated only two major rearrangements. Genetic diversity was analysed using resequencing data of seven diploid and one tetraploid Rosa species selected from various sections of the genus. Combining genetic and genomic approaches, we identified potential genetic regulators of key ornamental traits, including prickle density and the number of flower petals. A rose APETALA2/TOE homologue is proposed to be the major regulator of petal number in rose. This reference sequence is an important resource for studying polyploidization, meiosis and developmental processes, as we demonstrated for flower and prickle development. It will also accelerate breeding through the development of molecular markers linked to traits, the identification of the genes underlying them and the exploitation of synteny across Rosaceae.


Subject(s)
Genome, Plant/genetics , Rosa/genetics , Centromere/genetics , Chromosomes, Plant/genetics , Flowers/anatomy & histology , Flowers/genetics , Fragaria/genetics , Genetic Variation/genetics , Haploidy , In Situ Hybridization, Fluorescence , Phylogeny , Quantitative Trait Loci/genetics , Quantitative Trait, Heritable , Rosa/anatomy & histology , Sequence Analysis, DNA , Synteny/genetics
6.
Bone Joint J ; 97-B(1): 71-5, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25568416

ABSTRACT

The purpose of this study was to evaluate whether the serum level of interleukin 6 (IL-6) could be used to identify the persistence of infection after the first stage of a two-stage revision for periprosthetic joint infection. Between 2010 and 2011, we prospectively studied 55 patients (23 men, 32 women; mean age 69.5 years; 36 to 86) with a periprosthetic joint infection. Bacteria were identified in two intra-operative tissue samples during re-implantation in 16 patients. These cases were classified as representing persistent infection. To calculate a precise cut-off value which could be used in everyday clinical practice, a 3 x 2 contingency table was constructed and manually defined. We found that a serum IL-6 ≥ 13 pg/mL can be regarded as indicating infection: its positive-predictive value is 90.9%. A serum IL-6 ≤ 8 pg/mL can be regarded as indicating an absence of infection: its negative predictive value is 92.1%. The serum IL-6 level seems to be a reasonable marker for identifying persistent infection after the first stage of a revision joint arthroplasty and before attempting re-implantation.


Subject(s)
Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Knee/adverse effects , Interleukin-6/blood , Prosthesis-Related Infections/blood , Prosthesis-Related Infections/surgery , Adult , Aged , Aged, 80 and over , Area Under Curve , Arthroplasty, Replacement, Hip/methods , Arthroplasty, Replacement, Knee/methods , Biomarkers/blood , Cohort Studies , Confidence Intervals , Female , Follow-Up Studies , Humans , Male , Middle Aged , Preoperative Care/methods , Prospective Studies , Prosthesis-Related Infections/diagnosis , ROC Curve , Reoperation/methods , Risk Assessment , Sensitivity and Specificity , Statistics, Nonparametric , Treatment Outcome
7.
Neuroscience ; 277: 321-33, 2014 Sep 26.
Article in English | MEDLINE | ID: mdl-25043326

ABSTRACT

Neural networks ultimately arrive at functional output via interaction of the excitability of individual neurons and their synaptic interactions. We investigated the relationships between voltage-gated ion channel and neurotransmitter receptor mRNA levels in mouse spinal cord at four different postnatal time points (P5, P11, P17, and adult) and three different adult cord levels (cervical, thoracic, and lumbosacral) using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Our analysis and data visualization are novel in that we chose a focal group of voltage-gated channel subunits and transmitter receptor subunits, performed absolute quantitation of mRNA copy number for each gene from a sample, and used multiple correlation analyses and correlation matrices to detect patterns in correlated mRNA levels across all genes of interest. These correlation profiles suggest that postnatal maturation of the spinal cord includes changes among channel and receptor subunits that proceed from widespread co-regulation to more refined and distinct functional relationships.


Subject(s)
Membrane Proteins/metabolism , RNA, Messenger/metabolism , Spinal Cord/growth & development , Spinal Cord/metabolism , Acetylcholinesterase/metabolism , Animals , Cervical Vertebrae , GPI-Linked Proteins/metabolism , Lumbosacral Region , Mice, Inbred C57BL , Reverse Transcriptase Polymerase Chain Reaction , Thoracic Vertebrae
8.
Article in German | MEDLINE | ID: mdl-24863705

ABSTRACT

BACKGROUND: Almost one of four Germans is registered in a sports club. Nowadays, sport is acknowledged as an integral component of a healthy lifestyle. Numerous studies provide evidence of the benefits of sports on health. However, about 2 million sports injuries per year diminish the health benefits of sport. OBJECTIVE: (a) Description of the epidemiology of sports injuries in German sports club between 1987 and 2012 and (b) identification of focal areas for the development and implementation of prevention measures. METHODS: Continuous questionnaire-based injury monitoring of club sports injuries that have been reported to the respective sports insurance. Full survey among selected federal sports associations. RESULTS: Since 1987, a sample of 200,884 sports injuries has been established. About two thirds of the injuries are reported in soccer, handball, basketball, and volleyball, although only one third of all sports club members are registered in these team sports. The number of women's soccer injuries has risen from 7.5 to 15.6 %. Ankle injuries have decreased from 28.7 to 16.9 %. By contrast, the rate of knee injuries has increased from 18.4 to 20.3 %. Days of disability have dropped steadily since the 1990s. Inpatient hospital days have decreased from 10 to 5 days, whereas the share of injuries that needed surgery increased from 30 to 40 %. CONCLUSION: Team ball sports are still a clear focal area for injury prevention, as participation and injury risk are highest in this group. While the prevention of ankle injuries seems to be headed in the right direction, knee injuries are increasing. As team ball sports become more popular among women, who are more prone to severe knee injuries, prevention programs should be tailored toward the specific situation and needs of the targeted sports participants.


Subject(s)
Ankle Injuries/epidemiology , Ankle Injuries/prevention & control , Athletic Injuries/epidemiology , Athletic Injuries/prevention & control , Knee Injuries/epidemiology , Knee Injuries/prevention & control , Sports/statistics & numerical data , Absenteeism , Adolescent , Adult , Age Distribution , Aged , Ankle , Female , Germany/epidemiology , Hospitalization/statistics & numerical data , Humans , Incidence , Male , Middle Aged , Risk Factors , Sex Distribution , Sports/trends , Young Adult
9.
Z Gerontol Geriatr ; 46(4): 353-7, 2013 Jun.
Article in English | MEDLINE | ID: mdl-22903361

ABSTRACT

BACKGROUND: The chemical composition of the cerebrospinal fluid (CSF) is age-dependent. METHODS: Routine CSF parameters, the indications for lumbar puncture (LP), and the most frequent complications were retrospectively studied in patients older (n = 167) and younger (n = 36) than 65 years. RESULTS: In the absence of meningeal inflammation, the mean CSF lactate level of patients older than 65 years was slightly but significantly higher than the mean CSF lactate level of younger patients. The lactate level of patients with otherwise normal CSF findings correlated significantly with the age of the patients. In the absence of meningeal inflammation, the CSF-to-serum albumin ratio (QAlbumin) was significantly higher in older patients than in younger ones. The most frequent indication for LP, suspected infection of the central nervous system (CNS) (n = 110), was confirmed in 12.7% of patients. The only LP complication documented was headache in two patients. CONCLUSIONS: Elevations of QAlbumin and CSF lactate levels appear to be nonspecific findings in elderly patients. Suspected infections, the most frequent indication for LP, were confirmed by CSF analysis in more than 10% of patients. The very low complication rate of LP makes it a very valuable tool in the diagnostic routine for older patients with CNS diseases.


Subject(s)
Central Nervous System Infections/cerebrospinal fluid , Cerebrospinal Fluid/chemistry , Headache/cerebrospinal fluid , Headache/epidemiology , Lactic Acid/analysis , Postoperative Complications/cerebrospinal fluid , Spinal Puncture/statistics & numerical data , Aged , Aged, 80 and over , Biomarkers/cerebrospinal fluid , Central Nervous System Infections/epidemiology , Comorbidity , Female , Germany/epidemiology , Humans , Male , Middle Aged , Postoperative Complications/epidemiology , Prevalence
11.
Gynecol Oncol ; 128(2): 316-21, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23138135

ABSTRACT

OBJECTIVE: Uterine serous carcinoma (USC) constitutes 10% of uterine cancers but ~40% of deaths. Tumor size is a known prognostic factor in other solid tumors. In endometriod cancers it is one element used to identify the need for complete staging, while its significance in USC is debated. Therefore tumor size was examined as an independent prognostic factor. METHODS: Clinical and pathologic variables were recorded for 236 institutional patients, and those patients in the SEER database with USC. Chi-square and Fisher exact t-tests were utilized and survival data generated via Kaplan-Meier method; multivariate analysis was performed via cox-regression. RESULTS: The patients' mean age was 67.2 years (range 40-91). Survival ranged from 0 to 184 months (mean 42.8). We used a tumor size cut-off of 1cm and noted significant associations with myometrial invasion (p<0.0001), angiolymphatic invasion (p<0.0001), peritoneal washings (p=0.03), stage (p=0.015) and positive lymph nodes (p=0.05). Furthermore, recurrence was associated with larger tumors (p=0.03). In multivariate analysis, extra-uterine disease was the only factor associated with both recurrence and survival. Review of the SEER database noted association of larger tumors with lymph node involvement and a significant survival advantage with tumors <1cm in both univariate and multivariate analysis. CONCLUSIONS: Treatment options for USC are often predicated on the surgical stage and therefore components of the staging are vitally important. The 1cm tumor-size cut-off should be studied prospectively as a prognostic indicator of survival and recurrence in USC and considered for inclusion in USC staging.


Subject(s)
Cystadenocarcinoma, Serous/pathology , Uterine Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Cystadenocarcinoma, Serous/surgery , Female , Humans , Hysterectomy , Lymph Node Excision , Middle Aged , Neoplasm Staging , Prognosis , SEER Program , Uterine Neoplasms/surgery
12.
Allergy ; 67(12): 1530-7, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23066955

ABSTRACT

BACKGROUND: Analyses of the molecular basis underlying allergenicity and allergen cross-reactivity, as well as improvement of allergy diagnostics and therapeutics, are hampered by the lack of human monoclonal IgE antibodies and knowledge about their epitopes. Here, we addressed the consecutive generation and epitope delineation of a human monoclonal IgE against the prototypic allergen Bet v 1. METHODS: Phage-display scFv hybrid libraries of allergic donor-derived VH epsilon and synthetic VL were established from 107 mononuclear cells. An obtained scFv was converted into human immunoglobulin formats including IgE. Using variants of Bet v 1, the epitope of the antibody was mapped and extrapolated to other PR10 proteins. RESULTS: The obtained antibodies exhibited pronounced reactivity with Bet v 1, but were not reactive with the homologous PR10 protein Mal d 1. The epitope as defined by the IgE paratope and a set of chimeric Bet v 1 fusion proteins and fragments could be assigned to a C-terminal helix-structured motif comprised by amino acid residues 132-154, including the critical residue E149. Grafting this motif re-established the reactivity of the per se nonreactive Mal d 1 framework. Cross-reactivities predicted by primary structure analyses of different isoforms and PR10 proteins were verified by allergen chip-based analyses. CONCLUSIONS: The obtained results demonstrate that hybrid IgE repertoires represent a source for human antibodies with genuine paratopes. The IgE-derived information about the IgE epitope nature of Bet v 1 and homologues allows for detailed insights into molecular aspects of allergenicity and cross-reactivity within the PR10 protein family.


Subject(s)
Allergens/immunology , Antigens, Plant/immunology , Epitopes/immunology , Fagus/immunology , Immunoglobulin E/immunology , Plant Proteins/immunology , Allergens/chemistry , Amino Acid Sequence , Antibody Specificity , Antigens, Plant/chemistry , Cross Reactions/immunology , Epitopes/chemistry , Gene Library , Humans , Immunoglobulin E/chemistry , Immunoglobulin E/genetics , Immunoglobulin Heavy Chains/chemistry , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Variable Region/chemistry , Immunoglobulin Variable Region/genetics , Models, Molecular , Molecular Sequence Data , Peptide Library , Plant Proteins/chemistry , Protein Conformation , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Sequence Alignment
13.
Z Orthop Unfall ; 150(4): 415-9, 2012 Sep.
Article in German | MEDLINE | ID: mdl-22918827

ABSTRACT

The diagnosis and treatment of periprosthetic joint infections is a difficult situation for the attending physician. From the extensive literature, algorithms for diagnosis and therapy can be created. The aim of this study was to collect a representative survey of current concepts in the Federal States of the former West Germany and to compare them with those in the current literature. In 2011 orthopaedic and trauma clinics were surveyed anonymously in western Germany about diagnosis and treatment of periprosthetic infections. 450 questionnaires could be evaluated. Septic hip arthroplasty revisions were performed on average 12 (± 20)/year, septic knee arthroplasty revisions were performed on average 9 (± 17)/year. On average 205 (± 178) primary hip and 167 (± 155) primary knee arthroplasties were implanted/year. The analysis of the collected parameters is summarised in three tables. In the field of diagnostics, parameters such as CRP are determined. The interpretation, however, differs in more than 50 % of the hospitals on the relevant literature. Some important diagnostic parameters are not used. Therapy concepts are largely consistent with the literature. To a non-negligible extent, the vacuum-assisted therapy (approximately 30 % of hospitals) is used. In the literature it is described only for early infection. But even for use in early infection, there are very few data available. A unified diagnostic algorithm would be desirable.


Subject(s)
Arthritis/diagnosis , Arthritis/epidemiology , Arthritis/therapy , Practice Patterns, Physicians'/statistics & numerical data , Prosthesis-Related Infections/diagnosis , Prosthesis-Related Infections/therapy , Female , Germany/epidemiology , Health Care Surveys , Humans , Male , Prevalence , Prosthesis-Related Infections/epidemiology
14.
Neuroscience ; 168(1): 118-29, 2010 Jun 16.
Article in English | MEDLINE | ID: mdl-20211705

ABSTRACT

CbNa(v) and CbIH encode channels that carry voltage-gated sodium and hyperpolarization activated cation currents respectively in the crab, Cancer borealis. We cloned and sequenced full length cDNAs for both CbNa(v) and CbIH and found nine different regions of alternative splicing for the CbNa(v) gene and four regions of alternative splicing for CbIH. We used RT-PCR to determine tissue-specific differences in splicing of both channel genes among cardiac muscle, skeletal muscle, brain, and stomatogastric ganglion (STG) tissue. We then examined the splice variant isoforms present in single, unambiguously identified neurons of the STG. We found cell-type specific patterns of alternative splicing for CbNa(v), indicating unique cell-specific pattern of post-transcriptional modification. Furthermore, we detected possible differences in cellular localization of alternatively spliced CbNa(v) transcripts; distinct mRNA isoforms are present between the cell somata and the axons of the neurons. In contrast, we found no qualitative differences among different cell types for CbIH variants present, although this analysis did not represent the full spectrum of all possible CbIH variants. CbIH mRNA was not detected in axon samples. Finally, although cell-type specific patterns of splicing were detected for CbNa(v), the same cell type within and between animals also displayed variability in which splice forms were detected. These results indicate that channel splicing is differentially regulated at the level of single neurons of the same neural network, providing yet another mechanism by which cell-specific neuronal output can be achieved.


Subject(s)
Alternative Splicing , Ion Channels/genetics , Neurons/metabolism , Animals , Brachyura , Cloning, Molecular , DNA, Complementary/genetics , Electrophysiology , Ganglia, Invertebrate/metabolism , Ion Channel Gating , Ion Channels/metabolism , Nerve Net/cytology , Nerve Net/metabolism , Organ Specificity , Protein Isoforms/genetics , Protein Isoforms/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Sodium Channels/genetics , Sodium Channels/metabolism
15.
Arq. Inst. Biol. (Online) ; 77(1): 91-98, jan-mar, 2010. graf
Article in Portuguese | VETINDEX, LILACS | ID: biblio-1382054

ABSTRACT

O gênero Saccharomyces tem sido usado como indutor de resistência ou para controle biológico em muitos patossistemas. Neste trabalho objetivou-se a indução de fitoalexinas em mesocótilos de sorgo e cotilédones de soja pela levedura Saccharomyces boulardii na forma do produto comercial Floratil (Merck) (com 2 x 106 células/mg produto comercial - pc) e massa de células obtidas de meio líquido YEPG (primeiramente com 14 dias de cultivo e, posteriormente, com 7, 14, 21, 28 e 35 dias) ambos em concentrações de 0,005; 0,05; 0,5; 5; 15 e 25 mg/mL, além de filtrado desse meio nas concentrações de 0,01; 0,1; 1; 5; 10 e 20%. Como tratamentos controle utilizou-se água e S. cerevisiae (25 mg/mL de pc) para soja e água e acibenzolar-S-metil (ASM) (125 mg i.a./L) para sorgo. Em soja os três produtos apresentaram efeito dose-dependente, com ajustes de equações de 1° grau e R2 de 0,64; 0,94 e 0,98 não tendo efeito do tempo de cultivo da levedura na indução de fitoalexinas. Em sorgo apenas o filtrado e Floratil tiveram efeito dose-dependente com equação de 1° grau e R2 de 0,63 e 0,94 respectivamente e obteve-se nos diferentes dias de cultivo R2 de 0,62 com a massa de células somente. Portanto, pode-se evidenciar o potencial indutor de fitoalexinas dos produtos a base de S. boulardii para ensaios com indução de resistência em patossistemas envolvendo sorgo e soja.


Saccharomyces yeast compounds have been used as a resistance elicitor or for biological control in many pathosystems. Thus, the aim of this research was to verify the induction of phytoalexins in sorghum mesocotyls and soybean cotyledons by using Saccharomyces boulardii in the form of the commercial product Floratil (Merck) (with 2 x 106 cells/mg) and yeast-cell mass obtained from liquid culture in YEPG medium (with 7, 14, 21, 28 and 35 days old), both at concentrations of 0.005, 0.05, 0.5, 5, 15 and 25 mg/mL, as well as the filtrate of this medium in concentrations of 0.01, 0.1, 1, 5, 10 and 20%. The control treatments consisted of distilled water and S. cerevisiae (25 mg of commercial product per mL) for the soybean tests and distilled water and acibenzolar-S-methyl (125 mg of active ingredient per L) for the sorghum tests. In soybeans the three tested S. boulardii products presented a dose-dependent effect with R2 of 0.64, 0.94 and 0.98 for the culture filtrate, cell suspension and commercial product of S. boulardii, respectively, with no effect of culture time of yeasts on phytoalexin induction. In sorghum, only the culture filtrate and Floratil presented a dose-dependent effect, with R2 of 0.63 and 0.94, respectively, and the cell suspension of S. boulardii showed dependence of culture time with R2 of 0.62. Thus, S. boulardii and its derivates induce phytoalexins and have potential to be used as an elicitor for assays with induction resistance in pathosystems involving sorghum and soybean plants.


Subject(s)
Glycine max/physiology , Cotyledon/microbiology , Sorghum/physiology , Saccharomyces boulardii
16.
J Exp Biol ; 213(1): 128-36, 2010 Jan 01.
Article in English | MEDLINE | ID: mdl-20008369

ABSTRACT

The evolution of larger mammals resulted in a corresponding increase in peripheral nerve length. To ensure optimal nervous system functionality and survival, nerve conduction velocities were likely to have increased to maintain the rate of signal propagation. Increases of conduction velocities may have required alterations in one of the two predominant properties that affect the speed of neuronal transmission: myelination or axonal diameter. A plausible mechanism to explain faster conduction velocities was a concomitant increase in axonal diameter with evolving axonal length. The carboxy terminal tail domain of the neurofilament medium subunit is a determinant of axonal diameter in large caliber myelinated axons. Sequence analysis of mammalian orthologs indicates that the neurofilament medium carboxy terminal tail contains a variable lysine-serine-proline (KSP) repeat sub-domain flanked by two highly conserved sub-domains. The number of KSP repeats within this region of neurofilament medium varies among species. Interestingly, the number of repeats does not change within a species, suggesting that selective pressure conserved the number of repeats within a species. Mapping KSP repeat numbers onto consensus phylogenetic trees reveals independent KSP expansion events across several mammalian clades. Linear regression analyses identified three subsets of mammals, one of which shows a positive correlation in the number of repeats with head-body length. For this subset of mammals, we hypothesize that variations in the number of KSP repeats within neurofilament medium carboxy terminal tail may have contributed to an increase in axonal caliber, increasing nerve conduction velocity as larger mammals evolved.


Subject(s)
Axons/ultrastructure , Neurofilament Proteins/analysis , Neurofilament Proteins/genetics , Amino Acid Sequence , Animals , Humans , Mice , Molecular Sequence Data , Phylogeny , Rats , Repetitive Sequences, Amino Acid , Sequence Alignment
17.
Prog Neuropsychopharmacol Biol Psychiatry ; 32(5): 1257-62, 2008 Jul 01.
Article in English | MEDLINE | ID: mdl-18485555

ABSTRACT

The effect of varying the length and timing of photic stimulation in the dark phase of an L/D lighting cycle on behavioral despair was investigated in female Wistar rats. Animals were kept in a vivarium on an L/D 12 h:12 h light cycle (lights on at 0700 h) except for a single day of light exposure in an insulated chamber in the dark phase of the L/D schedule. Light pulses provided by an incandescent lamp (15- and 25-W, for Exps. 1 and 2, respectively) either 2-h (Exp. 1) or 30-min in length (Exp. 2) were administered to independent groups of rats (n=8 each) either in the early, middle or late hours of the dark phase of the L/D cycle in the insulated chamber. Light pulses were delivered beginning 2 1/2, 5 1/2 or 7 1/2 h (Exp. 1) or 3 1/4, 6 1/4 and 8 1/4 h (Exp. 2) after dark onset. Control animals were treated similarly except for photic stimulation. In each experiment, an additional group received a light pulse of the appropriate length both in the early and late portion of the dark phase (double double-pulse groups): beginning 2 1/2 and 7 1/2 h (Exp. 1) or 3 1/4 and 8 1/4 h (Exp. 2) after dark onset. All animals then underwent two forced swim tests separated by 24 h with the first test occurring in the light (starting at 1500 h) following the dark phase when photic stimulation was administered. Total duration of immobility in the second swim test was measured to gauge behavioral despair. In Exp. 1, the 2-h double double-pulse group showed significantly shorter immobility compared to controls (p<0.05). In Exp. 2, 30-min light pulse delivered late in the dark phase reduced immobility significantly compared to controls and all the other light-treated groups (p<0.01). Results indicate that photic stimulation may have antidepressant effect on behavioral despair depending on the timing and the duration of photic stimulation.


Subject(s)
Behavior, Animal/physiology , Circadian Rhythm/physiology , Darkness , Depressive Disorder/therapy , Phototherapy/methods , Analysis of Variance , Animals , Depressive Disorder/physiopathology , Disease Models, Animal , Female , Immobility Response, Tonic/radiation effects , Photic Stimulation/methods , Rats , Rats, Wistar , Swimming , Time Factors
18.
Cell Mol Life Sci ; 65(14): 2215-31, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18408887

ABSTRACT

The ion channel milieu present in a neuron in large part determines the inherent excitability of a given cell and is responsible for the translation of sensory transduction and synaptic input to axonal output. Intrinsic excitability is a dynamic process subject to multiple levels of regulation from channel gene expression to post-translational modifications that influence channel activity. The goal of this review is to provide an overview of some of the mechanisms by which channels can be modified in order to influence neuronal output. We focus on four levels of regulation: channel gene transcription, alternative splicing of channel transcripts, post-translational modifications that alter channel kinetics (phosphorylation), and subcellular localization and trafficking of channel proteins.


Subject(s)
Ion Channels/genetics , Ion Channels/metabolism , Neurons/metabolism , Alternative Splicing , Animals , Gene Expression , Humans , Kinetics , Models, Neurological , Neuronal Plasticity , Phosphorylation , Protein Processing, Post-Translational , Signal Transduction , Transcription, Genetic
19.
Biofouling ; 24(1): 59-66, 2008.
Article in English | MEDLINE | ID: mdl-18092216

ABSTRACT

A variety of macroalgae (Ceramium rubrum, Corallina officinalis, Palmaria palmata, Mastocarpus stellatus, Fucus vesiculosus, Cladophora rupestris, Ulva sp.) were investigated by scanning electron microscopy to visualize epiphytic colonizers. The macroalgae differed in terms of their epiphytic coverage of bacteria, fungi and diatoms. Macroalgae, largely devoid of epiphytic diatoms, were hypothesized to employ effective antifouling means to reduce epiphytic coverage, whilst heavily fouled macroalgae were proposed to lack antifouling strategies. To test these hypotheses from an allelochemical perspective with regard to fouling diatoms, dichloromethane-methanol (1:1) crude extracts of macroalgae were concentrated in dimethylsulfoxide and investigated in diatom attachment and proliferation assays using four benthic diatoms (Nitzschia sp., Navicula phyllepta, Navicula arenaria and Amphora sp.). Algal extracts exhibited a distinct pattern of activity against the test diatoms, suggesting a targeted and selective effect of macroalgal metabolites on individual fouling diatoms. The main outcome of this study was that visual inspection and quantitative categorization of epiphytic colonizers on macroalgal thalli could not be used to predict reliably whether macroalgae employed a chemical defense mechanism.


Subject(s)
Cell Adhesion/drug effects , Cell Proliferation/drug effects , Diatoms/drug effects , Chlorophyta/chemistry , Diatoms/cytology , Diatoms/physiology , North Sea , Phaeophyceae/chemistry , Rhodophyta/chemistry , Symbiosis/drug effects
20.
Hautarzt ; 58(11): 970-4, 2007 Nov.
Article in German | MEDLINE | ID: mdl-17618408

ABSTRACT

BACKGROUND: Despite the advantages of modern wound management, it is still employed too rarely because of higher costs and lack of information available to the medical staff. At the University Hospital Jena, the assortment of hydroactive wound dressings has been optimized, in order to increase acceptance and attain cost advantages. MATERIAL AND METHODS: The defined target sizes were differentiated according to economic and qualitative parameters. The economic parameters included the reduction in the total costs for wound management, adjusted for the case mix and the number of cases. Among the qualitative parameters were reducing the number of suppliers and the number of orders outside the standard offerings. RESULTS: Via standardization, the average expenses per case for hydroactive wound applications could be reduced by 10.3% and the average expenses per weighted German DRG by 15.9%. As a result of the reorganization of the assortment, the number of suppliers was reduced by 57.1% and two main and one secondary supplier were designated. The number of orders outside the standard assortment was reduced from 173 to 21 (87.8%). CONCLUSION: The standardization of the assortment of hydroactive wound applications has led to an increase in procedural efficiency and effectiveness at the University Hospital Jena, in addition to a reduction in the cost of material and in the number of suppliers.


Subject(s)
Bandages, Hydrocolloid/economics , Wounds and Injuries/economics , Wounds and Injuries/therapy , Cost Savings , Cost-Benefit Analysis , Costs and Cost Analysis , Diabetic Foot/therapy , Diagnosis-Related Groups/economics , Humans , Leg Ulcer/therapy , Pressure Ulcer/therapy , Wound Healing
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