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11.
Beata S. Lipska Irena Balasz-Chmielewska Lucyna Morzuch Kacper Wasielewski Dominika Vetter Halina Borzecka Dorota Drozdz Agnieszka Firszt-Adamczyk Ewa Gacka Tomasz Jarmolinski Joanna Ksiazek Elzbieta Kuzma-Mroczkowska Mieczyslaw Litwin Anna Medynska Magdalena Silska Maria Szczepanska Marcin Tkaczyk Anna Wasilewska Franz Schaefer Aleksandra Zurowska Janusz Limon 《Journal of applied genetics》2013,54(3):327-333
Hereditary nephrotic syndrome is caused by mutations in a number of different genes, the most common being NPHS2. The aim of the study was to identify the spectrum of NPHS2 mutations in Polish patients with the disease. A total of 141 children with steroid-resistant nephrotic syndrome (SRNS) were enrolled in the study. Mutational analysis included the entire coding sequence and intron boundaries of the NPHS2 gene. Restriction fragment length polymorphism (RFLP) and TaqMan genotyping assay were applied to detect selected NPHS2 sequence variants in 575 population-matched controls. Twenty patients (14 %) had homozygous or compound heterozygous NPHS2 mutations, the most frequent being c.1032delT found in 11 children and p.R138Q found in four patients. Carriers of the c.1032delT allele were exclusively found in the Pomeranian (Kashubian) region, suggesting a founder effect origin. The 14 % NPHS2 gene mutation detection rate is similar to that observed in other populations. The heterogeneity of mutations detected in the studied group confirms the requirement of genetic testing the entire NPHS2 coding sequence in Polish patients, with the exception of Kashubs, who should be initially screened for the c.1032delT deletion. 相似文献
12.
Water hyacinth Eichhornia crassipes is considered the most damaging aquatic weed in the world. However, few studies have quantified the impact of this weed economically and ecologically, and even fewer studies have quantified the benefits of its control. This paper focuses on water loss saving as the benefit derived from biological control of this plant between 1990 and 2013 at New Year’s Dam, Alicedale, Eastern Cape, South Africa. Estimates of water loss due to evapotranspiration from water hyacinth vary significantly; therefore, the study used three different rates, high, medium and low. A conservative raw agriculture value of R 0.26 per m3 was used to calculate the benefits derived by the water saved. The present benefit and cost values were determined using 10% and 5% discount rates. The benefit/cost ratio at the low evapotranspiration rate was less than one, implying that biological control was not economically viable but, at the higher evapotranspiration rates, the return justified the costs of biological control. However, at the marginal value product of water, the inclusion of the costs of damage to infrastructure, or the adverse effects of water hyacinth on biodiversity, would justify the use of biological control, even at the low transpiration rate. 相似文献
13.
The Tau/A152T mutation,a risk factor for frontotemporal‐spectrum disorders,leads to NR2B receptor‐mediated excitotoxicity 下载免费PDF全文
Astrid Sydow Frank JA Dennissen Zuzana Siskova Eckhard Mandelkow Eva‐Maria Mandelkow 《EMBO reports》2016,17(4):552-569
We report on a novel transgenic mouse model expressing human full‐length Tau with the Tau mutation A152T (hTauAT), a risk factor for FTD‐spectrum disorders including PSP and CBD. Brain neurons reveal pathological Tau conformation, hyperphosphorylation, mis‐sorting, aggregation, neuronal degeneration, and progressive loss, most prominently in area CA3 of the hippocampus. The mossy fiber pathway shows enhanced basal synaptic transmission without changes in short‐ or long‐term plasticity. In organotypic hippocampal slices, extracellular glutamate increases early above control levels, followed by a rise in neurotoxicity. These changes are normalized by inhibiting neurotransmitter release or by blocking voltage‐gated sodium channels. CA3 neurons show elevated intracellular calcium during rest and after activity induction which is sensitive to NR2B antagonizing drugs, demonstrating a pivotal role of extrasynaptic NMDA receptors. Slices show pronounced epileptiform activity and axonal sprouting of mossy fibers. Excitotoxic neuronal death is ameliorated by ceftriaxone, which stimulates astrocytic glutamate uptake via the transporter EAAT2/GLT1. In summary, hTauAT causes excitotoxicity mediated by NR2B‐containing NMDA receptors due to enhanced extracellular glutamate. 相似文献
14.
Priyanka Prakash Douglas Litwin Hong Liang Suparna Sarkar-Banerjee Drew Dolino Yong Zhou John F. Hancock Vasanthi Jayaraman Alemayehu A. Gorfe 《Biophysical journal》2019,116(2):179-183
Recent studies have shown that the small GTPase KRAS adopts multiple orientations with respect to the plane of anionic model membranes, whereby either the three C-terminal helices or the three N-terminal β-strands of the catalytic domain face the membrane. This has functional implications because, in the latter, the membrane occludes the effector-interacting surface. However, it remained unclear how membrane reorientation occurs and, critically, whether it occurs in the cell in which KRAS operates as a molecular switch in signaling pathways. Herein, using data from a 20 μs-long atomistic molecular dynamics simulation of the oncogenic G12V-KRAS mutant in a phosphatidylcholine/phosphatidylserine bilayer, we first show that internal conformational fluctuations of flexible regions in KRAS result in three distinct membrane orientations. We then show, using single-molecule fluorescence resonance energy transfer measurements in native lipid nanodiscs derived from baby hamster kidney cells, that G12V-KRAS samples three conformational states that correspond to the predicted orientations. The combined results suggest that relatively small energy barriers separate orientation states and that signaling-competent conformations dominate the overall population. 相似文献
15.
Hernandez-Trejo A B Estrada-Drouaillet JA López-Santillán C Rios-Velasco SE Varela-Fuentes R Rodríguez-Herrera E Osorio-Hernández 《Phyton》2019,88(1):47-54
The control of Spodoptera frugiperda is based
on synthetic insecticides, so some alternatives are the use of
entomopathogenic fungi (EF) and neem extract. The objective of
the study was to evaluate in vitro effectiveness of native EF and
neem extracts on S. frugiperda larvae. Six EF were identified by
DNA sequencing of ITS regions from three EF (Fusarium solani,
Metarrhizium robertsii, Nigrospora spherica and Penicillium
citrinum). They were evaluated in concentrations of 1 × 10⁸ spores/
mL. In addition, a second bioassay was carried out evaluating
only F. solani, M. robertsii and N. sphaerica and the addition
of vegetable oil. On the other hand, extraction of secondary
metabolites from neem seed (Azadirachta indica) was carried
out by performing, mass (g) and solvent volume (mL ethanol
and water) combinations, which were subjected to microwaves
and ultrasound. Subsequently, these extracts were evaluated
in concentrations of 3%, 4% and 5%. A survival analysis was
performed for each of the bioassays. With respect to the results
of the first bioassay, F. solani obtained a probability of survival of
0.476 on the seventh day, while in the second bioassay, M. robertsii
obtained 0.488 survival probability. This suggests that the expected
percentage of larvae that stay alive on the sixth day is 48.8%.
However, in the evaluation of the neem extract the combination
1:12/70% to 4% caused 84% mortality of larvae. The use of native
HE and neem extracts has potential for the control of S. frugiperda. 相似文献
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18.
Na-Ca exchange and the trigger for sarcoplasmic reticulum Ca release: studies in adult rabbit ventricular myocytes. 总被引:18,自引:1,他引:17 下载免费PDF全文
The importance of Na-Ca exchange as a trigger for sarcoplasmic reticulum (SR) Ca release remains controversial. Therefore, we measured whole-cell Ca currents (ICa), Na-Ca exchange currents (INaCa), cellular contractions, and intracellular Ca transients in adult rabbit cardiac myocytes. We found that changing pipette Na concentration markedly affected the relationship between cell shortening (or Ca transients) and voltage, but did not affect the Ca current-voltage relationship. We then inhibited Na-Ca exchange and varied SR content (by changing the number of conditioning pulses before each test pulse). Regardless of SR Ca content, the relationship between contraction and voltage was bell-shaped in the absence of Na-Ca exchange. Next, we rapidly and completely blocked ICa by applying nifedipine to cells. Cellular shortening was variably reduced in the presence of nifedipine. The component of shortening blocked by nifedipine had a bell-shaped relationship with voltage, whereas the "nifedipine-insensitive" component of contraction increased with voltage. With the SR disabled (ryanodine and thapsigargin pretreatment), ICa could initiate late-peaking contractions that were approximately 70% of control amplitude. In contrast, nifedipine-insensitive contractions could not be elicited in the presence of ryanodine and thapsigargin. Finally, we recorded reverse Na-Ca exchange currents that were activated by membrane depolarization. The estimated sarcolemmal Ca flux occurring by Na-Ca exchange (during voltage clamp steps to +30 mV) was approximately 10-fold less than that occurring by ICa. Therefore, Na-Ca exchange alone is unlikely to raise cytosolic Ca concentration enough to directly activate the myofilaments. We conclude that reverse Na-Ca exchange can trigger SR Ca release. Because of the sigmoidal relationship between the open probability of the SR Ca release channel and pCa, the effects of ICa and INaCa may not sum in a linear fashion. Rather, the two triggers may act synergistically in the modulation of SR release. 相似文献
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20.
Marijn Rutgers Daniël BF Saris Wouter JA Dhert Laura B Creemers 《Arthritis research & therapy》2010,12(3):R114