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41.
Jean‐Noël Octave Nathalie Pierrot Susana Ferao Santos Natalia N. Nalivaeva Anthony J. Turner 《Journal of neurochemistry》2013,126(2):183-190
Despite intensive studies of the secretase‐mediated processing of the amyloid precursor protein (APP) to form the amyloid β‐peptide (Aβ), in relation to Alzheimer's disease (AD), no new therapeutic agents have reached the clinics based on reducing Aβ levels through the use of secretase inhibitors or immunotherapy. Furthermore, the normal neuronal functions of APP and its various metabolites still remain under‐investigated and unclear. Here, we highlight emerging areas of APP function that may provide new insights into synaptic development, cognition, and gene regulation. By modulating expression levels of endogenous APP in primary cortical neurons, the frequency and amplitude of calcium oscillations is modified, implying a key role for APP in maintaining neuronal calcium homeostasis essential for synaptic transmission. Disruption of this homeostatic mechanism predisposes to aging and AD. Synaptic spine loss is a feature of neurogeneration resulting in learning and memory deficits, and emerging evidence indicates a role for APP, probably mediated via one or more of its metabolites, in spine structure and functions. The intracellular domain of APP (AICD) has also emerged as a key epigenetic regulator of gene expression controlling a diverse range of genes, including APP itself, the amyloid‐degrading enzyme neprilysin, and aquaporin‐1. A fuller understanding of the physiological and pathological actions of APP and its metabolic network could provide new opportunities for therapeutic intervention in AD. 相似文献
42.
Maja Martic Ida Noémi Jakab-Simon Lærke Tvedebrink Haahr Wilfred Raymond Hagen Hans Erik Mølager Christensen 《Journal of biological inorganic chemistry》2013,18(2):261-276
Heterometallic [AgFe3S4] iron–sulfur clusters assembled in wild-type Pyrococcus furiosus ferredoxin and two variants, D14C and D14H, are characterized. The crystal structure of the [AgFe3S4] D14C variant shows that the silver(I) ion is indeed part of the cluster and is coordinated to the thiolate group of residue 14. Cyclic voltammetry shows one redox pair with a reduction potential of +220 mV versus the standard hydrogen electrode which is assigned to the [AgFe3S4]2+/+ couple. The oxidized form of the [AgFe3S4] D14C variant is stable in the presence of dioxygen, whereas the oxidized forms of the [AgFe3S4] wild type and D14H variants convert to the [Fe3S4] ferredoxin form. The monovalent d 10 silver(I) ion stabilizes the [Fe3S4]+/0 cluster fragment, as opposed to divalent d 10 metal ions, resulting in more than 0.4 V difference in reduction potentials between the silver(I) and, e.g., zinc(II) heterometallic [MFe3S4] ferredoxins. The trend in reduction potentials for the variants containing the [AgFe3S4] cluster is wild type ≤ D14C < D14H and shows the same trend as reported for the variants containing the [Fe3S4] cluster, but is different from the D14C < D14H < wild type trend reported for the [Fe4S4] ferredoxin. The similarity in the reduction potential trend for the variants containing the heterometallic [AgFe3S4] cluster and the [Fe3S4] cluster can be rationalized in terms of the electrostatic influence of the residue 14 side chains, rather than the dissociation constant of this residue, as is the case for [Fe4S4] ferredoxins. The trends in reduction potentials are in line with there being no electronic coupling between the silver(I) ion and the Fe3S4 fragment. 相似文献
43.
44.
Sushil Bhandari Joon No Lee Young-Il Kim In-Koo Nam Su-Jung Kim Se-Jin Kim 《Organogenesis》2016,12(2):78-93
Very long chain fatty acids are required for sphingolipid synthesis, lipid homeostasis, myelin formation, epidermal permeability, and retinal function. Seven different enzymes are known to be involved in the elongation cycle of fatty acids, with different chain-length specificities. Elovl1 is one of those enzymes whose function has been linked mainly to the synthesis of sphingolipids and the epidermal barrier. However, the role of Elovl1 in organogenesis is not clear. In zebrafish, 2 Elovl1 genes, elovl1a and elovl1b, are highly expressed in the swim bladder, and elovl1b is also expressed in the kidney. We found that both elovl1 knockdown embryos contain increased levels of long chain fatty acids from carbon number 14 to 20 as compared to control embryos. Oil-Red-O staining shows that yolk lipid consumption is greatly reduced, whereas lipid droplets accumulate within the swim bladder. Notably, knockdown of either elovl1a or elovl1b affects the expression of genes involved in swim bladder development and impairs inflation of the swim bladder. Consistent with its expression in the pronephros, knockdown of elovl1b alone affects the expression of genes required for kidney development and reduces renal clearance. Our findings strongly suggest that both elovl1 genes are a key determinant of swim bladder and kidney development in zebrafish, which may be comparatively applicable to lung and kidney development in humans. 相似文献
45.
Sébastien Breurec Noémie Vanel Petulla Bata Lo?c Chartier Alain Farra Lo?c Favennec Thierry Franck Tamara Giles-Vernick Jean-Chrysostome Gody Liem Binh Luong Nguyen Manuella Onambélé Clotaire Rafa? Romy Razakandrainibe Laura Tondeur Vianney Tricou Philippe Sansonetti Muriel Vray 《PLoS neglected tropical diseases》2016,10(1)
Background
In Sub-Saharan Africa, infectious diarrhea is a major cause of morbidity and mortality. A case-control study was conducted to identify the etiology of diarrhea and to describe its main epidemiologic risk factors among hospitalized children under five years old in Bangui, Central African Republic.Methods
All consecutive children under five years old hospitalized for diarrhea in the Pediatric Complex of Bangui for whom a parent’s written consent was provided were included. Controls matched by age, sex and neighborhood of residence of each case were included. For both cases and controls, demographic, socio-economic and anthropometric data were recorded. Stool samples were collected to identify enteropathogens at enrollment. Clinical examination data and blood samples were collected only for cases.Results
A total of 333 cases and 333 controls was recruited between December 2011 and November 2013. The mean age of cases was 12.9 months, and 56% were male. The mean delay between the onset of first symptoms and hospital admission was 3.7 days. Blood was detected in 5% of stool samples from cases. Cases were significantly more severely or moderately malnourished than controls. One of the sought-for pathogens was identified in 78% and 40% of cases and controls, respectively. Most attributable cases of hospitalized diarrhea were due to rotavirus, with an attributable fraction of 39%. Four other pathogens were associated with hospitalized diarrhea: Shigella/EIEC, Cryptosporidium parvum/hominis, astrovirus and norovirus with attributable fraction of 9%, 10%, 7% and 7% respectively. Giardia intestinalis was found in more controls than cases, with a protective fraction of 6%.Conclusions
Rotavirus, norovirus, astrovirus, Shigella/EIEC, Cryptosporidium parvum/hominis were found to be positively associated with severe diarrhea: while Giardia intestinalis was found negatively associated. Most attributable episodes of severe diarrhea were associated with rotavirus, highlighting the urgent need to introduce the rotavirus vaccine within the CAR’s Expanded Program on Immunization. The development of new medicines, vaccines and rapid diagnostic tests that can be conducted at the bedside should be high priority for low-resource countries. 相似文献46.
Mary Henry Noêmi GalAn Katherine Teasdale Renata Prado Harpreet Amar Marina S. Rays Lesley Roberts Pedro Siqueira Gilles de Wildt Marcos Virmond Pranab K. Das 《PLoS neglected tropical diseases》2016,10(3)
BackgroundLeprosy is a leading cause of preventable disability worldwide. Delay in diagnosis of patients augments the transmission of infection, and allows progression of disease and more severe disability. Delays in diagnosis greater than ten years have been reported in Brazil. To reduce this delay, it is important to identify factors that hinder patients from presenting to doctors, and those that delay doctors from diagnosing patients once they have presented. This study aimed to explore factors associated with the delayed diagnosis of leprosy in Brazil.
Methodology/ Principal Findings
This is an exploratory study using a self-constructed questionnaire delivered to patients attending three leprosy referral clinics across three states in Brazil. Data were analysed to determine associations between variables and the time taken for participants to present to the health-service, and between variables and the time taken for doctors to diagnose participants once they had presented. Participants who suspected they had leprosy but feared community isolation were 10 times more likely to wait longer before consulting a doctor for their symptoms (OR 10.37, 95% CI 2.18–49.45, p = 0.003). Participants who thought their symptoms were not serious had a threefold greater chance of waiting longer before consulting than those who did (OR 3.114, 95% CI 1.235–7.856, p = 0.016). Forty-two point six per cent of participants reported initially receiving a diagnosis besides leprosy. These had a three times greater chance of receiving a later diagnosis of leprosy compared to those not misdiagnosed or not given a diagnosis (OR 2.867, 95% CI 1.288–6.384, p = 0.010).Conclusions/ Significance
This study implies a need for patient education regarding leprosy symptoms and the reduction of stigma to encourage patients to present. The high rate of misdiagnosis reported suggests a need to increase clinician suspicion of leprosy. Further education regarding disease symptoms in medical school curriculums may be advisable. 相似文献47.
A. Sauerwald M. Niggl J. Puppe A. Prescher M. Scaal G. K. Noé S. Schiermeier M. Warm C. Eichler 《PloS one》2016,11(2)
Introduction
Pectopexy, a laparoscopic method for prolapse surgery, showed promising results in recent literature. Further improving this approach by reducing surgical time may decrease complication rates and patient morbidity. Since laparoscopic suturing is a time consuming task, we propose a single suture /mesh ileo-pectineal ligament fixation as opposed to the commonly used continues approach.Methods
Evaluation was performed on human non-embalmed, fresh cadaver pelves. A total of 33 trials was performed. Eight female pelves with an average age of 75, were used. This resulted in 16 available ligaments. Recorded parameters were ultimate load, displacement at failure and stiffness.Results
The ultimate load for the mesh + simplified single “interrupted” suture (MIS) group was 35 (± 12) N and 48 (± 7) N for the mesh + continuous suture (MCS) group. There was no significant difference in the ultimate load between both groups (p> 0.05). This was also true for displacement at failure measured at 37 (± 12) mm and 36 (±5) mm respectively. There was also no significant difference in stiffness and failure modes.Conclusion
Given the data above we must conclude that a continuous suture is not necessary in laparoscopic mesh / ileo-pectineal ligament fixation during pectopexy. Ultimate load and displacement at failure results clearly indicate that a single suture is not inferior to a continuous approach. The use of two single sutures may improve ligamental fixation. However, overall stability should not benefit since the surgical mesh remains the limiting factor. 相似文献48.
The lateral resolution of continuous wave (CW) stimulated emission depletion (STED) microscopy is enhanced about 12% by applying annular‐shaped amplitude modulation to the radially polarized excitation beam. A focused annularly filtered radially polarized excitation beam provides a more condensed point spread function (PSF), which contributes to enhance effective STED resolution of CW STED microscopy. Theoretical analysis shows that the FWHM of the effective PSF on the detection plane is smaller than for conventional CW STED. Simulation shows the donut‐shaped PSF of the depletion beam and confocal optics suppress undesired PSF sidelobes. Imaging experiments agree with the simulated resolution improvement. 相似文献
49.
Ichikawa H No H Takei S Takashimizu I Yue F Cui L Ogiwara N Johkura K Nishimoto Y Sasaki K 《Cryobiology》2007,54(3):290-293
Cryopreservation of embryonic stem (ES) cells is essential to establish them as a resource for regenerative therapy. We evaluated survival adhesion rate, cell structure, gene expression, and multipotency of frozen and thawed embryoid bodies (EBs) derived from mouse ES cells. EBs were cryopreserved using the BICELL and the Program Freezer. After one week the EBs were thawed and cultured. EBs prepared in the Program Freezer had the highest survival adhesion (Program Freezer; 55-69%, BICELL; 30-38%). Though many cells in the thawed EBs were damaged, some were not, especially those prepared in the Program Freezer. RT-PCR analysis showed that genes characteristic of the three embryonic germ layers were expressed in thawed EBs cultured for one week. EBs transplanted into mice formed teratomas consisting of cells derived from the three germ layers. In conclusion, EBs frozen in the Program Freezer had higher survival adhesion rates compared to the BICELL and formed differentiated cells characteristic of the three embryonic germ layers. 相似文献
50.
Sarah Noël Martin Ouellet Patrick Galois François-Joseph Lapointe 《Conservation Genetics》2007,8(3):599-606
Urban development is a major cause of habitat loss and fragmentation. Few studies, however, have dealt with fragmentation
in an urban landscape. In this paper, we examine the genetic structure of isolated populations of the eastern red-backed salamander
(Plethodon cinereus) in a metropolitan area. We sampled four populations located on a mountain in the heart of Montréal (Québec, Canada), which
presents a mosaic of forested patches isolated by roads, graveyards and buildings. We assessed the genetic structure of these
populations using microsatellite loci and compared it to the genetic structure of four populations located in a continuous
habitat in southern Québec. Our results indicate that allelic richness and heterozygosity are lower in the urban populations.
Exact differentiation tests and pairwise F
ST also show that the populations found in the fragmented habitat are genetically differentiated, whereas populations located
in the continuous habitat are genetically homogeneous. These results raise conservation concerns for these populations as
well as for rare or threatened species inhabiting urban landscapes. 相似文献