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Release of calcium from intracellular stores and subsequent uptake by mitochondria are essential for the candidacidal activity of an N-terminal peptide of human lactoferrin
OBJECTIVES:
Earlier studies showed that mitochondrial damage is a hallmark of the candidacidal activity of an N-terminal peptide of human lactoferrin, further referred to as hLF(1-11). Since uptake of Ca(2+) by mitochondria may be essential for their activation, the aim of this study was to define the role of Ca(2+) in killing of Candida albicans by the hLF(1-11) peptide.
METHODS:
The effect of compounds interfering with Ca(2+) homeostasis on the hLF(1-11)-induced candidacidal activity, changes in mitochondrial membrane potential, and reactive oxygen species production were evaluated using a killing assay, rhodamine 123 staining, and 2',7'-dichlorofluorescein diacetate, respectively. The increase in cellular Ca(2+) content was measured using (45)Ca(2+).
RESULTS:
Our results revealed that Ruthenium Red, which inhibits the mitochondrial Ca(2+)-uniporter and the voltage-sensitive Ca(2+) release from internal stores, blocked (P<0.05) the hLF(1-11)-induced candidacidal activity as well as changes in the membrane potential of mitochondria, and reactive oxygen species production. Oxalate, which precipitates Ca(2+) in intracellular organelles, decreased (P<0.05) the peptide-induced changes in the membrane potential of mitochondria, reactive oxygen species production, and candidacidal activity. Furthermore, the Ca(2+) ionophore ionomycin combined with high CaCl(2) concentrations enhanced the hLF(1-11)-induced candidacidal activity. Moreover, hLF(1-11) caused an influx of Ca(2+) from the extracellular medium into C. albicans reaching a three-fold increase at 2 h, whereas no increase was found in unexposed cells. In agreement, the Ca(2+)-chelator EGTA blocked the peptide-induced candidacidal activity.
CONCLUSIONS:
Ca(2+) release from intracellular stores, probably through subsequent mitochondrial Ca(2+) uptake, is essential for the hLF(1-11)-induced candidacidal activity
Internal thiols and reactive oxygen species in the candidacidal activity exerted by a N-terminal peptide of human lactoferrin.
The R156H variation in IL-12Rβ1 is not a mutation
Palamaro et al. describe a child with recurrent bronchopneumonia and very high IgE levels in which a variation, R156H, was found in the IL12RB1 gene that encodes the IL-12Rβ1 chain. Based on the absence of this variation in 50 unrelated individuals they conclude it is a mutation. We (van de Vosse and van Dissel) feel there is no reason to suspect a defect in IL-12 signaling based on the clinical data, nor evidence for a functional defect in IL-12 signaling in this patient. In addition, the variation is not novel and known as a polymorphism. Without any functional evidence that R156H is a mutation, the current claim is not substantiated. Palamaro et al. respond to argue that the amino acid substitution, R156H described in the described case exerts a summatory effect, as a genetic cofactor, along with an additional and still unidentified molecular alteration of the same pathway
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
RIVM-Centrum Infectieziektebestrijding : Strategie 2016-2021
This strategy describes the ambitions of the Centre for Infectious Disease Control (CIb) for the coming years. It concerns the changes that the CIb considers to be necessary, rather than a summary of activities. Thanks to the efforts made by prevention and vaccination programmes, in the Netherlands there is relatively little disease and death as a result of infectious disease. However, there continue to be some important challenges. The rise of resistance to antibiotics is worrying and calls for an integral and coordinated plan of action. In addition, the success of the National Immunisation Programme (NIP) is not guaranteed: in order to maintain sustainable support from parents and professionals, it is necessary to continually invest in the programme and in communication with professionals and the public. Furthermore, it is important to gain insight into zoonotic threats (i.e. diseases that can be transferred from animals to humans). The number of people with sexually transmitted diseases in high risk groups such as prostitutes and drug users has also risen and it is very important that efforts to prevent these are continued. In order to control infectious diseases properly, it is also important to have insight into national and international trends and changes in this area. In terms of organisation, the aim is to further improve the structure within which infectious diseases are managed. In conclusion, good interaction between the national and international activities of the CIb is very important.In deze strategie staan de ambities van het Centrum Infectieziektebestrijding (CIb) voor de komende jaren beschreven. Het gaat hierbij om de veranderingen die het CIb noodzakelijk acht; het is niet zozeer een opsomming van activiteiten. Dankzij inspanningen voor preventie- en vaccinatieprogramma's is er in Nederland relatief weinig ziekte en sterfte als gevolg van infectieziekten. Wel zijn er belangrijke uitdagingen. De opkomst van antibioticaresistentie is zorgwekkend en vraagt om een integrale en gecoördineerde aanpak. Daarnaast is het succes van het rijksvaccinatieprogramma (RVP) niet vanzelfsprekend: om het brede draagvlak onder ouders en professionals te behouden is het noodzakelijk dat om voortdurend te blijven investeren in het programma en de communicatie met professionals en het publiek. Verder is het belangrijk inzicht te hebben in zoönotische bedreigingen (ziekten die van dier op mens overgaan). Ook is het aantal mensen met een seksueel overdraagbare aandoeningen bij 'hoogrisicogroepen', zoals prostituees en drugsgebruikers, gestegen waardoor inspanningen om ze te voorkomen belangrijk blijven. Om infectieziekten goed te kunnen bestrijden is het bovendien van belang inzicht te hebben in nationale en internationale trends en veranderingen op dit gebied. In organisatorisch opzicht gaat het om een verdere verbetering van de structuur waarmee infectieziekten worden bestreden. Ten slotte is een goede wisselwerking van belang tussen de nationale en internationale activiteiten van het CIb.Ministry of Health, Welfare and Spor
National Institute for Public Health and the Environment (RIVM) Centre for Infectious Disease Control : Strategy 2016-2021
This strategy describes the ambitions of the Centre for Infectious Disease Control (CIb) for the coming years. It concerns the changes that the CIb considers to be necessary, rather than a summary of activities. Thanks to the efforts made by prevention and vaccination programmes, in the Netherlands there is relatively little disease and death as a result of infectious disease. However, there continue to be some important challenges. The rise of resistance to antibiotics is worrying and calls for an integral and coordinated plan of action. In addition, the success of the National Immunisation Programme (NIP) is not guaranteed: in order to maintain sustainable support from parents and professionals, it is necessary to continually invest in the programme and in communication with professionals and the public. Furthermore, it is important to gain insight into zoonotic threats (i.e. diseases that can be transferred from animals to humans). The number of people with sexually transmitted diseases in high risk groups such as prostitutes and drug users has also risen and it is very important that efforts to prevent these are continued. In order to control infectious diseases properly, it is also important to have insight into national and international trends and changes in this area. In terms of organisation, the aim is to further improve the structure within which infectious diseases are managed. In conclusion, good interaction between the national and international activities of the CIb is very importantIn deze strategie staan de ambities van het Centrum Infectieziektebestrijding (CIb) voor de komende jaren beschreven. Het gaat hierbij om de veranderingen die het CIb noodzakelijk acht; het is niet zozeer een opsomming van activiteiten. Dankzij inspanningen voor preventie- en vaccinatieprogramma's is er in Nederland relatief weinig ziekte en sterfte als gevolg van infectieziekten. Wel zijn er belangrijke uitdagingen. De opkomst van antibioticaresistentie is zorgwekkend en vraagt om een integrale en gecoördineerde aanpak. Daarnaast is het succes van het rijksvaccinatieprogramma (RVP) niet vanzelfsprekend: om het brede draagvlak onder ouders en professionals te behouden is het noodzakelijk dat om voortdurend te blijven investeren in het programma en de communicatie met professionals en het publiek. Verder is het belangrijk inzicht te hebben in zoönotische bedreigingen (ziekten die van dier op mens overgaan). Ook is het aantal mensen met een seksueel overdraagbare aandoeningen bij 'hoogrisicogroepen', zoals prostituees en drugsgebruikers, gestegen waardoor inspanningen om ze te voorkomen belangrijk blijven. Om infectieziekten goed te kunnen bestrijden is het bovendien van belang inzicht te hebben in nationale en internationale trends en veranderingen op dit gebied. In organisatorisch opzicht gaat het om een verdere verbetering van de structuur waarmee infectieziekten worden bestreden. Ten slotte is een goede wisselwerking van belang tussen de nationale en internationale activiteiten van het CIbMinisterie van VW
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