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131.
Juergen Dukart Ferath Kherif Karsten Mueller Stanislaw Adaszewski Matthias L. Schroeter Richard S. J. Frackowiak Bogdan Draganski for the Alzheimer's Disease Neuroimaging Initiative 《PLoS computational biology》2013,9(4)
The failure of current strategies to provide an explanation for controversial findings on the pattern of pathophysiological changes in Alzheimer''s Disease (AD) motivates the necessity to develop new integrative approaches based on multi-modal neuroimaging data that captures various aspects of disease pathology. Previous studies using [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and structural magnetic resonance imaging (sMRI) report controversial results about time-line, spatial extent and magnitude of glucose hypometabolism and atrophy in AD that depend on clinical and demographic characteristics of the studied populations. Here, we provide and validate at a group level a generative anatomical model of glucose hypo-metabolism and atrophy progression in AD based on FDG-PET and sMRI data of 80 patients and 79 healthy controls to describe expected age and symptom severity related changes in AD relative to a baseline provided by healthy aging. We demonstrate a high level of anatomical accuracy for both modalities yielding strongly age- and symptom-severity- dependant glucose hypometabolism in temporal, parietal and precuneal regions and a more extensive network of atrophy in hippocampal, temporal, parietal, occipital and posterior caudate regions. The model suggests greater and more consistent changes in FDG-PET compared to sMRI at earlier and the inversion of this pattern at more advanced AD stages. Our model describes, integrates and predicts characteristic patterns of AD related pathology, uncontaminated by normal age effects, derived from multi-modal data. It further provides an integrative explanation for findings suggesting a dissociation between early- and late-onset AD. The generative model offers a basis for further development of individualized biomarkers allowing accurate early diagnosis and treatment evaluation. 相似文献
132.
133.
Felicia M. Wagner Ilija Brizic Adrian Prager Tihana Trsan Maja Arapovic Niels A. W. Lemmermann Jürgen Podlech Matthias J. Reddehase Frederic Lemnitzer Jens Bernhard Bosse Martina Gimpfl Lisa Marcinowski Margaret MacDonald Heiko Adler Ulrich H. Koszinowski Barbara Adler 《PLoS pathogens》2013,9(7)
Human cytomegalovirus (HCMV) forms two gH/gL glycoprotein complexes, gH/gL/gO and gH/gL/pUL(128,130,131A), which determine the tropism, the entry pathways and the mode of spread of the virus. For murine cytomegalovirus (MCMV), which serves as a model for HCMV, a gH/gL/gO complex functionally homologous to the HCMV gH/gL/gO complex has been described. Knock-out of MCMV gO does impair, but not abolish, virus spread indicating that also MCMV might form an alternative gH/gL complex. Here, we show that the MCMV CC chemokine MCK-2 forms a complex with the glycoprotein gH, a complex which is incorporated into the virion. We could additionally show that mutants lacking both, gO and MCK-2 are not able to produce infectious virus. Trans-complementation of these double mutants with either gO or MCK-2 showed that both proteins can promote infection of host cells, although through different entry pathways. MCK-2 has been extensively studied in vivo by others. It has been shown to be involved in attracting cells for virus dissemination and in regulating antiviral host responses. We now show that MCK-2, by forming a complex with gH, strongly promotes infection of macrophages in vitro and in vivo. Thus, MCK-2 may play a dual role in MCMV infection, as a chemokine regulating the host response and attracting specific target cells and as part of a glycoprotein complex promoting entry into cells crucial for virus dissemination. 相似文献
134.
Matthias Schultze-Kraft Markus Diesmann Sonja Grün Moritz Helias 《PLoS computational biology》2013,9(4)
The functional significance of correlations between action potentials of neurons is still a matter of vivid debate. In particular, it is presently unclear how much synchrony is caused by afferent synchronized events and how much is intrinsic due to the connectivity structure of cortex. The available analytical approaches based on the diffusion approximation do not allow to model spike synchrony, preventing a thorough analysis. Here we theoretically investigate to what extent common synaptic afferents and synchronized inputs each contribute to correlated spiking on a fine temporal scale between pairs of neurons. We employ direct simulation and extend earlier analytical methods based on the diffusion approximation to pulse-coupling, allowing us to introduce precisely timed correlations in the spiking activity of the synaptic afferents. We investigate the transmission of correlated synaptic input currents by pairs of integrate-and-fire model neurons, so that the same input covariance can be realized by common inputs or by spiking synchrony. We identify two distinct regimes: In the limit of low correlation linear perturbation theory accurately determines the correlation transmission coefficient, which is typically smaller than unity, but increases sensitively even for weakly synchronous inputs. In the limit of high input correlation, in the presence of synchrony, a qualitatively new picture arises. As the non-linear neuronal response becomes dominant, the output correlation becomes higher than the total correlation in the input. This transmission coefficient larger unity is a direct consequence of non-linear neural processing in the presence of noise, elucidating how synchrony-coded signals benefit from these generic properties present in cortical networks. 相似文献
135.
Xiaohong Wang David Brandt Narsinh L. Thakur Matthias Wiens Renato Batel Heinz C. Schröder Werner E. G. Müller 《Phytochemistry Reviews》2013,12(3):369-390
Marine organisms especially those that live sessile, as sponges, are well known to have specific relationships with a great variety of microorganisms including bacteria and fungi. As most simple metazoan phylum, the Porifera, which emerged first during the transition from the non-Metazoa to the Metazoa from the common ancestor, comprise wide arrays of recognition molecules, both for Gram-negative bacteria and for Gram-positive bacteria as well as for fungi. They react specifically with effector molecules to inhibit or kill the invading microorganisms. The elicitation and the subsequent effector reactions of the sponges towards these microbes are outlined. However, besides of the elimination of bacteria and fungi, some of those taxa are kept as symbionts of the sponges, allowing them, for example, to accumulate the essential element manganese or to synthesize carotinoids. The sponges produce low-molecular-weight bioactive compounds, secondary metabolites, to eliminate the microorganisms. In addition, they are armed with cationic antimicrobial peptides allowing them to defend against invasive microorganisms and, in parallel, to kill or repel also metazoan invaders. The broad range of chemically and functionally different compounds qualifies the Porifera as the most important animal phylum to be exploited as a source for the isolation of new potential drugs. First molecular biological strategies have been outlined to obtain those compounds in a sustainable way, by producing them recombinantly. 相似文献
136.
André Mischo Oliver Ohlenschläger Ramadurai Ramachandran Matthias Görlach 《Biomolecular NMR assignments》2013,7(1):47-49
The resonance assignment of an amino-terminal pyroglutamic acid containing peptide derived from the E6 protein of human papillomavirus (HPV) type 51 in complex with PDZ domain 2 of hDlg/SAP-97 is reported. The assignments include 1H, 13C and 15N resonances for the protein and peptide in the complex and all of the peptide’s pyroglutamic acid nuclei. 相似文献
137.
Catrina Mugglin Gilles Wandeler Janne Estill Matthias Egger Nicole Bender Mary-Ann Davies Olivia Keiser 《PloS one》2013,8(2)
Background
In adults it is well documented that there are substantial losses to the programme between HIV testing and start of antiretroviral therapy (ART). The magnitude and reasons for loss to follow-up and death between HIV diagnosis and start of ART in children are not well defined.Methods
We searched the PubMed and EMBASE databases for studies on children followed between HIV diagnosis and start of ART in low-income settings. We examined the proportion of children with a CD4 cell count/percentage after after being diagnosed with HIV infection, the number of treatment-eligible children starting ART and predictors of loss to programme. Data were extracted in duplicate.Results
Eight studies from sub-Saharan Africa and two studies from Asia with a total of 10,741 children were included. Median age ranged from 2.2 to 6.5 years. Between 78.0 and 97.0% of HIV-infected children subsequently had a CD4 cell count/percentage measured, 63.2 to 90.7% of children with an eligibility assessment met the eligibility criteria for the particular setting and time and 39.5 to 99.4% of the eligible children started ART. Three studies reported an association between low CD4 count/percentage and ART initiation while no association was reported for gender. Only two studies reported on pre-ART mortality and found rates of 13 and 6 per 100 person-years.Conclusion
Most children who presented for HIV care met eligibility criteria for ART. There is an urgent need for strategies to improve the access to and retention to care of HIV-infected children in resource-limited settings. 相似文献138.
Rapid species diversifications provide fascinating insight into the development of biodiversity in time and space. Most biological radiations studied to date, for example that of cichlid fishes or Andean lupines, are confined to isolated geographical areas like lakes, islands or island-like regions. Using DNA sequence data of the ribosomal internal transcribed spacer (ITS) for many species of the Poa alliance, a group comprising about 775 C3 grass species, revealed rapid and parallel diversifications in various parts of the world. Some of these radiations are restricted to isolated areas like the Andes, whereas others are typical of the lowlands of mainly the northern hemisphere. These radiations thus are not restricted to island-like areas and are seemingly actively ongoing. The ages of the diversifying clades are estimated to be 2.5–0.23 million years (Myr). Conservative diversification rates in the Poa alliance amount to 0.89–3.14 species per Myr, thus are in the order of, or even exceeding, other instances of well-known radiations. The grass radiations of the mainly cold-adapted Poa alliance coincide with the Late Tertiary global cooling, which resulted in the retreat of forests and the subsequent formation of cold-adapted grasslands especially in the northern, but also in parts of the southern hemisphere. The cold tolerance, suggested to be one of the ecological key innovations, may have been acquired during the early diversification of the subfamily Pooideae, but became significant millions of years later during the Pliocene/Pleistocene radiation of the Poa alliance. 相似文献
139.
Hye Jin Yoo Soon Young Hwang Ho Cheol Hong Hae Yoon Choi Sae Jeong Yang Dong Seop Choi Sei Hyun Baik Matthias Blüher Byung-Soo Youn Kyung Mook Choi 《PloS one》2013,8(2)
Objective
Progranulin and C1q/TNF-related protein-3 (CTRP3) were recently discovered as novel adipokines which may link obesity with altered regulation of glucose metabolism, chronic inflammation and insulin resistance.Research Design and Methods
We examined circulating progranulin and CTRP3 concentrations in 127 subjects with (n = 44) or without metabolic syndrome (n = 83). Furthermore, we evaluated the relationship of progranulin and CTRP3 levels with inflammatory markers and cardiometabolic risk factors, including high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), estimated glomerular filtration rate (eGFR), and adiponectin serum concentrations, as well as carotid intima-media thickness (CIMT).Results
Circulating progranulin levels are significantly related with inflammatory markers, hsCRP (r = 0.30, P = 0.001) and IL-6 (r = 0.30, P = 0.001), whereas CTRP3 concentrations exhibit a significant association with cardiometabolic risk factors, including waist circumference (r = −0.21), diastolic blood pressure (r = −0.21), fasting glucose (r = −0.20), triglyceride (r = −0.34), total cholesterol (r = −0.25), eGFR (r = 0.39) and adiponectin (r = 0.26) levels. Serum progranulin concentrations were higher in patients with metabolic syndrome than those of the control group (199.55 [179.33, 215.53] vs. 185.10 [160.30, 204.90], P = 0.051) and the number of metabolic syndrome components had a significant positive correlation with progranulin levels (r = 0.227, P = 0.010). In multiple regression analysis, IL-6 and triglyceride levels were significant predictors of serum progranulin levels (R 2 = 0.251). Furthermore, serum progranulin level was an independent predictor for increased CIMT in subjects without metabolic syndrome after adjusting for other cardiovascular risk factors (R 2 = 0.365).Conclusions
Serum progranulin levels are significantly associated with systemic inflammatory markers and were an independent predictor for atherosclerosis in subjects without metabolic syndrome.Trial Registration
ClinicalTrials.gov NCT01668888相似文献140.