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| 2. |
- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 3. |
- Schael, S, et al.
(författare)
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Precision electroweak measurements on the Z resonance
- 2006
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 5. |
- Kucharz, Krzysztof, et al.
(författare)
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NMDA receptor stimulation induces reversible fission of the neuronal endoplasmic reticulum.
- 2009
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:4
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Tidskriftsartikel (refereegranskat)abstract
- With few exceptions the endoplasmic reticulum (ER) is considered a continuous system of endomembranes within which proteins and ions can move. We have studied dynamic structural changes of the ER in hippocampal neurons in primary culture and organotypic slices. Fluorescence recovery after photobleaching (FRAP) was used to quantify and model ER structural dynamics. Ultrastructure was assessed by electron microscopy. In live cell imaging experiments we found that, under basal conditions, the ER of neuronal soma and dendrites was continuous. The smooth and uninterrupted appearance of the ER changed dramatically after glutamate stimulation. The ER fragmented into isolated vesicles in a rapid fission reaction that occurred prior to overt signs of neuronal damage. ER fission was found to be independent of ER calcium levels. Apart from glutamate, the calcium ionophore ionomycin was able to induce ER fission. The N-methyl, D-aspartate (NMDA) receptor antagonist MK-801 inhibited ER fission induced by glutamate as well as by ionomycin. Fission was not blocked by either ifenprodil or kinase inhibitors. Interestingly, sub-lethal NMDA receptor stimulation caused rapid ER fission followed by fusion. Hence, ER fission is not strictly associated with cellular damage or death. Our results thus demonstrate that neuronal ER structure is dynamically regulated with important consequences for protein mobility and ER luminal calcium tunneling.
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| 6. |
- Ng, Ai Na, et al.
(författare)
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Dendritic EGFP-STIM1 activation after type I metabotropic glutamate and muscarinic acetylcholine receptor stimulation in hippocampal neuron.
- 2011
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Ingår i: Journal of Neuroscience Research. - : Wiley. - 1097-4547 .- 0360-4012. ; 89:8, s. 1235-1244
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Tidskriftsartikel (refereegranskat)abstract
- Several signaling pathways in neurons engage the endoplasmic reticulum (ER) calcium store by triggering calcium release. After release, ER calcium levels must be restored. In many non-neuronal cell types, this is mediated by store-operated calcium entry (SOCE), a cellular homeostatic mechanism that activates specialized store-operated calcium channels (SOC). Although much evidence supports the existence of SOCE in neurons, its importance has been difficult to determine because of the abundance of calcium channels expressed and the lack of SOC-specific pharmacological agents. We have explored the function of the SOCE-inducing protein STIM1 in neurons. In EGFP-STIM1-expressing hippocampal neurons, the sarco- and endoplasmic reticulum calcium ATPase (SERCA) inhibitor thapsigargin caused rapid aggregation (i.e., activation) of STIM1 in soma and dendrites. Upon STIM1 activation by thapsigargin, a dramatic reduction in STIM1 mobility was detected by fluorescence recovery after photobleaching (FRAP). By triggering release of ER calcium with 3,5-dihydroxyphenylglycine (DHPG) or carbachol (Cch), agonists of type I metabotropic glutamate receptors (mGluR) and muscarinic acetylcholine receptors (mAChR), respectively, STIM1 was activated, and calcium entry (likely to represent SOCE) occurred in dendrites. It is therefore possible that neuronal SOCE is activated by physiological stimuli, some of which may alter the postsynaptic calcium signaling properties. © 2011 Wiley-Liss, Inc.
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| 7. |
- Ng, Ai Na, et al.
(författare)
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Endoplasmic reticulum dynamics in hippocampal dendritic spines induced by agonists of type I metabotropic glutamate but not by muscarinic acetylcholine receptors.
- 2011
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Ingår i: Synapse. - : Wiley. - 1098-2396 .- 0887-4476. ; 65:4, s. 351-355
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Tidskriftsartikel (refereegranskat)abstract
- Neurons in the hippocampus exhibit subpopulations of dendritic spines that contain endoplasmic reticulum (ER). ER in spines is important for synaptic activity and its associated Ca(2+) signaling. The dynamic distribution of ER to spines is regulated by diacylglycerol and partly mediated by protein kinase C, metalloproteinases and γ-secretase. In this study, we explored whether pharmacological activation of type I metabotropic glutamate receptors (mGluRs) and muscarinic acetylcholine receptors (mAChRs) known to activate phospholipase C would have any effect on spine ER content. We found that DHPG (100 μM) but not carbachol (10 μM) caused a reduction in the number of spines with ER. We further found that ER Ca(2+) depletion triggered by thapsigargin (200 nM) had no effect on ER localization in spines.
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| 8. |
- Ng, Ai Na
(författare)
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Endoplasmic reticulum function in dendrites and dendritic spines of hippocampal neurons
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the hippocampus, dendritic spines are compartmentalized postsynaptic micro-domains in the excitatory synapse. Subsets of bigger and mushroom-shaped hippocampal dendritic spines contain tubules and cisterns of endoplasmic reticulum (ER) that are connected to the soma and dendrites of the neuron. These ER containing spines differ in their ability to retain ER. We hypothesized a functional coupling of the ER to the plasma membrane (PM) via protein-protein interaction at specialized junctions, which we believe to anchor ER within spines. Although the molecular composition of such an ER-plasma membrane junction (ERPMJ) is yet to be elucidated, we showed that a subset of ERPMJs containing type I transmembrane proteins sensitive to phorbol ester induced metalloproteinase and subsequent gamma-secretase mediated remodelling, and that these proteins may be involved in regulating spine ER dynamics. The gamma-secretase is a multimeric complex with presenilin protein as the catalytic component. Findings have implicated mutations in the presenilin genes clinically associated to familial Alzheimer’s disease (FAD) with altered store-operated calcium entry (SOCE) response. SOCE is a cellular homeostatic mechanism that is activated to restore the depleted ER calcium store via specialized store-operated calcium channels (SOC) localized in the PM. With SOCE-inducing protein STIM1, we explored the effect of a FAD M146V mutation in presenilin-1 (PS1) on spine ER dynamics as well as on STIM1 function. In EGFP-STIM1-expressing hippocampal neurons established from wild-type and FAD PS1 mutant mice, we used 3,5-dihydroxyphenylglycine (DHPG) and carbachol, agonist of type I metabotropic glutamate receptors and muscarinic acetylcholine receptors to trigger calcium release from the ER via IP3R. Surprisingly, STIM1 activation appeared not to be affected by the PS1-M146V mutation although SOCE was impaired. Separately, we showed that DHPG or carbachol stimulation in PS1-M146V neurons led to a significant ER loss from spines that was exclusively mediated by mechanisms controlling ER entry into spines. We hypothesized that the PS1-M146V mutation altered yet to be elucidated mechanisms regulating ER entry into spines, and which may well contribute to synaptic dysfunction in FAD. Looking forward, there is value in future research to elucidate novel molecules and signaling pathways vis-a-vis gamma-secretase and presenilin activity to spine ER dynamics.
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| 9. |
- Ng, Ai Na, et al.
(författare)
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{gamma}-Secretase and metalloproteinase activity regulate the distribution of endoplasmic reticulum to hippocampal neuron dendritic spines.
- 2008
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Ingår i: FASEB Journal. - : Wiley. - 1530-6860 .- 0892-6638. ; 22:8, s. 2832-2842
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Tidskriftsartikel (refereegranskat)abstract
- The neuronal endoplasmic reticulum (ER) contributes to many physiological and pathological processes in the brain. A subset of dendritic spines on hippocampal neurons contains ER that may contribute to synapse-specific intracellular signaling. Distribution of ER to spines is dynamic, but knowledge of the regulatory mechanisms is lacking. In live cell imaging experiments we now show that cultured hippocampal neurons rapidly lost ER from spines after phorbol ester treatment. ER loss was reduced by inhibiting gamma-secretase (DAPT at 2 microM) and metalloproteinase (TAPI-0 and GM6001 at 4 microM) activity. Inhibition of protein kinase C also diminished loss of ER by preventing exit of ER from spines. Furthermore, gamma-secretase and metalloproteinase inhibition, in the absence of phorbol ester, triggered a dramatic increase in spine ER content. Metalloproteinases and gamma-secretase cleave several transmembrane proteins. Many of these substrates are known to localize to adherens junctions, a structural specialization with which spine ER interacts. One interesting possibility is thus that ER content within spines may be regulated by proteolytic activity affecting adherens junctions. Our data demonstrate a hitherto unknown role for these two proteolytic activities in regulating dynamic aspects of cellular ultrastructure, which is potentially important for cellular calcium homeostasis and several intracellular signaling pathways.-Ng, A. N., Toresson, H. gamma-Secretase and metalloproteinase activity regulate the distribution of endoplasmic reticulum to hippocampal neuron dendritic spines.
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