1,193 research outputs found
The permittivity in the Huttner-Barnett theory of QED in dielectrics
No full textHuttner and Barnett's interpretation of the function they call
as the dielectric permittivity is crucial in
practical applications of their theory. We show explicitly that is the permittivity but that their microscopic model can only
describe certain types of permittivity
Investigating cell turnover in the healthy and diseased adult human brain
No full textFor decades it was thought that cells that lost in the human central nervous system because of ageing or disease – different from other cell tissues – cannot be replaced and that in humans all neurons are generated during prenatal development. However, over the last 20 years, it became obvious that there is a certain level of adult neurogenesis in most mammals that mainly occurs in the dentate gyrus and the subventricular zone. Whether or not findings from animal studies also hold true in humans was difficult to study as direct evidence – as obtained in animals from genomic labeling using for instance nucleosides like BrdU – was not feasible in humans because of ethical considerations.The establishment of the so-called radiocarbon technique, a method taking advantage of the above-ground nuclear bomb tests during the Cold War to retrospectively birth date cells by determination of the 12C/14C ratio in genomic DNA – allowed to investigate the age and the turnover dynamics of cells in various human tissues. Applying this technique we here (i) studied whether there is adult neurogenesis in the healthy human brain, specifically within the hippocampus, (ii) studied whether there is adult neurogenesis in the diseased human brain, specifically in response to cortical stroke, and (iii) investigated the age and growth dynamics of brain tumors, specifically benign meningiomas.In essence we demonstrate (i) that there is a lifelong adult neurogenesis within the human hippocampus and provide an integrated model of hippocampal cell turnover dynamics, (ii) that there is no significant induction of cortical neurogenesis following ischemic cortical stroke in humans, and (iii) that the age of benign meningiomas is significantly older than that of more malignant brain tumors. The clinical implications of these findings are discussed and research projects for future studies identified.List of scientific papersI. Spalding KL, Bergmann O, Alkass K, Bernard S, Salehpour M, Huttner HB, Boström E, Westerlund I, Vial C, Buchholz BA, Possnert G, Mash DC, Druid H, Frisén J. Dynamics of hippocampal neurogenesis in adult humans. Cell. 2013; 153:1219-27. https://doi.org/10.1016/j.cell.2013.05.002 II. Huttner HB, Bergmann O, Salehpour M, Rácz A, Tatarishvili J, Lindgren E, Csonka T, Csiba L, Hortobágyi T, Méhes G, Englund E, Solnestam BW, Zdunek S, Scharenberg C, Ström L, Ståhl P, Sigurgeirsson B, Dahl A, Schwab S, Possnert G, Bernard S, Kokaia Z, Lindvall O, Lundeberg J, Frisén J. The age and genomic integrity of neurons after cortical stroke in humans. Nat Neurosci. 2014; 17:801-3. https://doi.org/10.1038/nn.3706 III. Hagen B. Huttner , Olaf Bergmann , Mehran Salehpour, Raouf El Cheikhs, Makoto Nakamura, Angelo Tortora, Roland Coras, Elisabet Englund, Ilker Y. Eyüpoglu, Joji B. Kuramatsu, Stephan P. Kloska, Iris Kaschka, Arnd Doerfler, Stefan Schwab, Göran Possnert, Samuel Bernard and Jonas Frisén. The age and growth dynamics of meningiomas. [Submitted]</p
Neocortical neurogenesis in development and evolution-Human-specific features
No full textIn this review, we focus on human-specific features of neocortical neurogenesis in development and evolution. Two distinct topics will be addressed. In the first section, we discuss the expansion of the neocortex during human evolution and concentrate on the human-specific gene ARHGAP11B. We review the ability of ARHGAP11B to amplify basal progenitors and to expand a primate neocortex. We discuss the contribution of ARHGAP11B to neocortex expansion during human evolution and its potential implications for neurodevelopmental disorders and brain tumors. We then review the action of ARHGAP11B in mitochondria as a regulator of basal progenitor metabolism, and how it promotes glutaminolysis and basal progenitor proliferation. Finally, we discuss the increase in cognitive performance due to the ARHGAP11B-induced neocortical expansion. In the second section, we focus on neocortical development in modern humans versus Neanderthals. Specifically, we discuss two recent findings pointing to differences in neocortical neurogenesis between these two hominins that are due to a small number of amino acid substitutions in certain key proteins. One set of such proteins are the kinetochore-associated proteins KIF18a and KNL1, where three modern human-specific amino acid substitutions underlie the prolongation of metaphase during apical progenitor mitosis. This prolongation in turn is associated with an increased fidelity of chromosome segregation to the apical progenitor progeny during modern human neocortical development, with implications for the proper formation of radial units. Another such key protein is transketolase-like 1 (TKTL1), where a single modern human-specific amino acid substitution endows TKTL1 with the ability to amplify basal radial glia, resulting in an increase in upper-layer neuron generation. TKTL1's ability is based on its action in the pentose phosphate pathway, resulting in increased fatty acid synthesis. The data imply greater neurogenesis during neocortical development in modern humans than Neanderthals due to TKTL1, in particular in the developing frontal lobe.ARHGAP11B is present in the genomes of Neanderthals and modern humans but not chimpanzee and increases the size of the neocortex during development. (The Neanderthal brain is a virtual reconstruction [Kochiyama et al., 2018, Sci. Rep. 8, 6296].) Amino acid substitutions in key proteins, such as KIF18a, KNL1, SPAG5, and TKTL1, are found in modern humans but not in chimpanzee and Neanderthals and underlie increased metaphase length and reduced lagging chromosomes during apical progenitor mitosis (KIF18a, KNL1, SPAG5) or increased basal radial glia abundance and upper-layer neuron number (TKTL1). imagePeer reviewe
How to improve antibiotic awareness campaigns: Findings of a WHO global survey
No full textIntroduction We aimed to examine the characteristics of antibiotic awareness campaigns (AAC) conducted on a national or regional level since 2010. Methods In October 2016, the WHO invited stakeholders involved in the planning or conduct of AACs to answer a web questionnaire. We solicited general information about the characteristics of the AAC, with a particular focus on key messages supporting optimal use of antibiotics. Results Stakeholders in 93 countries were contacted and 55 countries responded. Overall, 60 AACs from 16 low/middle-income countries (LMIC) and 31 high-income countries were identified. Forty-five campaigns (75%) were conducted on a national level and most of them (47/60; 78%) were organised by public health authorities and publicly funded. There were no major differences between LMICs and high-income countries in the types of key messages. The scientifically questionable 'Finish your prescription' slogan was used by 31 AACs (52%). A One Health approach was mentioned in 13/60 AACs (22%). Most messages were universally applicable; adaptation to locally prevalent public misconceptions was not systematic. The evaluation of the impact of campaigns was still incomplete, as only 18 AACs (30%) assessed their impact on antibiotic use. Conclusion For future AACs, it seems essential to base messages more rigorously on scientific evidence, context specificities and behavioural change theory. A new generation of messages that encourage first-choice use of narrow spectrum antibiotics is needed, reflecting international efforts to preserve broad spectrum antibiotic classes. Evaluation of the impact of AACs remains suboptimal
Blijft nitrofurantoïne eerste keus bij cystitis?
No full textbespreking van Huttner A, Verhaegh E, Harbarth S, Muller A, Mouton J. Nitrofurantoin revisited: a systematic review and meta-analysis of controlled trials. JAC 2015; 70:2456-246
N-cadherin specifies first asymmetry in developing neurons
No full textThe precise polarization and orientation of developing neurons is essential for the correct wiring of the brain. In pyramidal excitatory neurons, polarization begins with the sprouting of opposite neurites, which later define directed migration and axo-dendritic domains. We here show that endogenous N-cadherin concentrates at one pole of the newborn neuron, from where the first neurite subsequently emerges. Ectopic N-cadherin is sufficient to favour the place of appearance of the first neurite. The Golgi and centrosome move towards this newly formed morphological pole in a second step, which is regulated by PI3K and the actin/microtubule cytoskeleton. Moreover, loss of function experiments in vivo showed that developing neurons with a non-functional N-cadherin misorient their cell axis. These results show that polarization of N-cadherin in the immediate post-mitotic stage is an early and crucial mechanism in neuronal polarity.sponsorship: We thank C Kalcheim, O Griesbeck, F Calderon de Anda and RY Tsien for providing material; C Haffner and F Calderon de Anda for technical help and A Attardo for providing the tub-mGFP mouse line. This work was made possible by the type 3 large-infrastructure support InfraMouse by the Flanders Hercules Foundation (ZW09-03). This work was partially supported by the Flanders Fund for Scientific Research (FWO G 0.666.10N), the Federal Office for Scientific Affairs (IUAP p6/43) and Flemish Government Methusalem Grant to CGD. EFF has been in part supported by an EMBO fellowship (ASTF: 369.00-2007). FV was supported by the Italian Institute of Technology (Satellite Unit in Molecular Neuroscience). (Flanders Hercules Foundation|ZW09-03, Flanders Fund for Scientific Research (FWO)|G 0.666.10N, Federal Office for Scientific Affairs (IUAP)|p6/43, Flemish Government, EMBO|ASTF: 369.00-2007, Italian Institute of Technology (Satellite Unit in Molecular Neuroscience))status: Publishe
Dual-Lagrangian description adapted to quantum optics in dispersive and dissipative dielectric media
No full textInternational audienceWe develop a dual description of quantum optics adapted to dielectric systems without magnetic property. Our formalism, which is shown to be equivalent to the standard one within some dipolar approximations discussed in the article, is applied to the description of polaritons in dielectric media. We show that the dual formalism leads to the Huttner-Barnett equations [B. Huttner and S. M. Barnett, Phys. Rev. A 46, 4306 (1992)] for QED in dielectric systems. More generally, we discuss the role of electromagnetic duality in the quantization procedure for optical systems and derive the structure of the dynamical laws in the various representations
Kepelring, Barbara E. (Death, 1875-07-04)
No full textAddress: 24 Garden Ave.Age at death: 6moPg 245/1875/96/F W S/City/Dr. H. Huttner/J. Schreiber/Carthage Rd.Original record filed in drawer labeled 'Kennedy-Kesse'
Defective secretion of islet hormones in chromogranin-B deficient mice.
No full textGranins are major constituents of dense-core secretory granules in neuroendocrine cells, but their function is still a matter of debate. Work in cell lines has suggested that the most abundant and ubiquitously expressed granins, chromogranin A and B (CgA and CgB), are involved in granulogenesis and protein sorting. Here we report the generation and characterization of mice lacking chromogranin B (CgB-ko), which were viable and fertile. Unlike neuroendocrine tissues, pancreatic islets of these animals lacked compensatory changes in other granins and were therefore analyzed in detail. Stimulated secretion of insulin, glucagon and somatostatin was reduced in CgB-ko islets, in parallel with somewhat impaired glucose clearance and reduced insulin release, but normal insulin sensitivity in vivo. CgB-ko islets lacked specifically the rapid initial phase of stimulated secretion, had elevated basal insulin release, and stored and released twice as much proinsulin as wildtype (wt) islets. Stimulated release of glucagon and somatostatin was reduced as well. Surprisingly, biogenesis, morphology and function of insulin granules were normal, and no differences were found with regard to beta-cell stimulus-secretion coupling. We conclude that CgB is not required for normal insulin granule biogenesis or maintenance in vivo, but is essential for adequate secretion of islet hormones. Consequentially CgB-ko animals display some, but not all, hallmarks of human type-2 diabetes. However, the molecular mechanisms underlying this defect remain to be determined
Argyrophilic carcinoma of the male breast. A neuroendocrine tumor containing predominantly chromogranin B (secretogranin I)
No full textArgyrophilic tumors were diagnosed in 28 of 134 (20.8%) consecutive male patients who had a carcinoma of the breast removed between 1961 and 1990. Histologically, most argyrophilic tumors showed uniform cellularity and prevalent expansive growth. Ultrastructural observation disclosed the presence of electron-dense cored granules in the cytoplasm of the tumor cells. By immunocytochemistry, 17 of 28 argyrophilic tumors (60.7%) contained chromogranin B (secretogranin I)-immunoreactive cells, whereas chromogranin A was present in four of these 17 tumors only (14.2%). Immunoblotting studies showed chromogranin B immunoreactivity similar to that found in normal neuroendocrine cells. Despite these findings, which would argue for a distinct morphologic and immunochemical entity, no statistically significant differences between argyrophilic and common male breast carcinomas were found when a number of clinicopathologic features and relapse-free survival were considered
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