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421.
Yoann Augagneur Lise Jaubert Matthieu Schiavoni Niseema Pachikara Aprajita Garg Sahar Usmani-Brown Donna Wesolowski Skye Zeller Abhisek Ghosal Emmanuel Cornillot Hamid M. Said Priti Kumar Sidney Altman Choukri Ben Mamoun 《The Journal of biological chemistry》2013,288(28):20558-20567
The human malaria parasite Plasmodium falciparum is absolutely dependent on the acquisition of host pantothenate for its development within human erythrocytes. Although the biochemical properties of this transport have been characterized, the molecular identity of the parasite-encoded pantothenate transporter remains unknown. Here we report the identification and functional characterization of the first protozoan pantothenate transporter, PfPAT, from P. falciparum. We show using cell biological, biochemical, and genetic analyses that this transporter is localized to the parasite plasma membrane and plays an essential role in parasite intraerythrocytic development. We have targeted PfPAT to the yeast plasma membrane and showed that the transporter complements the growth defect of the yeast fen2Δ pantothenate transporter-deficient mutant and mediates the entry of the fungicide drug, fenpropimorph. Our studies in P. falciparum revealed that fenpropimorph inhibits the intraerythrocytic development of both chloroquine- and pyrimethamine-resistant P. falciparum strains with potency equal or better than that of currently available pantothenate analogs. The essential function of PfPAT and its ability to deliver both pantothenate and fenpropimorph makes it an attractive target for the development and delivery of new classes of antimalarial drugs. 相似文献
422.
Sahar Jafari Nivlouei M. Soltani Joo Carvalho Rui Travasso Mohammad Reza Salimpour Ebrahim Shirani 《PLoS computational biology》2021,17(6)
The dynamics of tumor growth and associated events cover multiple time and spatial scales, generally including extracellular, cellular and intracellular modifications. The main goal of this study is to model the biological and physical behavior of tumor evolution in presence of normal healthy tissue, considering a variety of events involved in the process. These include hyper and hypoactivation of signaling pathways during tumor growth, vessels’ growth, intratumoral vascularization and competition of cancer cells with healthy host tissue. The work addresses two distinctive phases in tumor development—the avascular and vascular phases—and in each stage two cases are considered—with and without normal healthy cells. The tumor growth rate increases considerably as closed vessel loops (anastomoses) form around the tumor cells resulting from tumor induced vascularization. When taking into account the host tissue around the tumor, the results show that competition between normal cells and cancer cells leads to the formation of a hypoxic tumor core within a relatively short period of time. Moreover, a dense intratumoral vascular network is formed throughout the entire lesion as a sign of a high malignancy grade, which is consistent with reported experimental data for several types of solid carcinomas. In comparison with other mathematical models of tumor development, in this work we introduce a multiscale simulation that models the cellular interactions and cell behavior as a consequence of the activation of oncogenes and deactivation of gene signaling pathways within each cell. Simulating a therapy that blocks relevant signaling pathways results in the prevention of further tumor growth and leads to an expressive decrease in its size (82% in the simulation). 相似文献
423.
Brian Hu Marina E. Garrett Peter A. Groblewski Douglas R. Ollerenshaw Jiaqi Shang Kate Roll Sahar Manavi Christof Koch Shawn R. Olsen Stefan Mihalas 《PLoS computational biology》2021,17(9)
The maintenance of short-term memories is critical for survival in a dynamically changing world. Previous studies suggest that this memory can be stored in the form of persistent neural activity or using a synaptic mechanism, such as with short-term plasticity. Here, we compare the predictions of these two mechanisms to neural and behavioral measurements in a visual change detection task. Mice were trained to respond to changes in a repeated sequence of natural images while neural activity was recorded using two-photon calcium imaging. We also trained two types of artificial neural networks on the same change detection task as the mice. Following fixed pre-processing using a pretrained convolutional neural network, either a recurrent neural network (RNN) or a feedforward neural network with short-term synaptic depression (STPNet) was trained to the same level of performance as the mice. While both networks are able to learn the task, the STPNet model contains units whose activity are more similar to the in vivo data and produces errors which are more similar to the mice. When images are omitted, an unexpected perturbation which was absent during training, mice often do not respond to the omission but are more likely to respond to the subsequent image. Unlike the RNN model, STPNet produces a similar pattern of behavior. These results suggest that simple neural adaptation mechanisms may serve as an important bottom-up memory signal in this task, which can be used by downstream areas in the decision-making process. 相似文献
424.
Leila Satarian Mohammad Javan Sahar Kiani Maryam Hajikaram Javad Mirnajafi-Zadeh Hossein Baharvand 《PloS one》2013,8(8)
Background
Degeneration of retinal ganglion cells (RGCs) is a common occurrence in several eye diseases. This study examined the functional improvement and protection of host RGCs in addition to the survival, integration and neuronal differentiation capabilities of anterior specified neural progenitors (NPs) following intravitreal transplantation.Methodology/Principal Findings
NPs were produced under defined conditions from human induced pluripotent stem cells (hiPSCs) and transplanted into rats whose optic nerves have been crushed (ONC). hiPSCs were induced to differentiate into anterior specified NPs by the use of Noggin and retinoic acid. The hiPSC-NPs were labeled by green fluorescent protein or a fluorescent tracer 1,1′ -dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) and injected two days after induction of ONC in hooded rats. Functional analysis according to visual evoked potential recordings showed significant amplitude recovery in animals transplanted with hiPSC-NPs. Retrograde labeling by an intra-collicular DiI injection showed significantly higher numbers of RGCs and spared axons in ONC rats treated with hiPSC-NPs or their conditioned medium (CM). The analysis of CM of hiPSC-NPs showed the secretion of ciliary neurotrophic factor, basic fibroblast growth factor, and insulin-like growth factor. Optic nerve of cell transplanted groups also had increased GAP43 immunoreactivity and myelin staining by FluoroMyelin™ which imply for protection of axons and myelin. At 60 days post-transplantation hiPSC-NPs were integrated into the ganglion cell layer of the retina and expressed neuronal markers.Conclusions/Significance
The transplantation of anterior specified NPs may improve optic nerve injury through neuroprotection and differentiation into neuronal lineages. These NPs possibly provide a promising new therapeutic approach for traumatic optic nerve injuries and loss of RGCs caused by other diseases. 相似文献425.
Françoise Bernard Azar Hassanpour Gila Gholizadeh Sahar Hassannejad Zahede Chaghari 《Acta Physiologiae Plantarum》2011,33(2):431-436
In this study, the ability of safflower-isolated root cultures to produce yellow pigments was tested. Initially, the growth of isolated roots in static liquid medium was evaluated with different volumes of culture medium. A volume of 6 ml of medium per flask of 250 ml gave the best growth performance and, in this condition of culture, production of pigments from isolated roots treated or not by light has been determined by spectrophotometry (321 and 400 nm). Under these conditions, the production of yellow pigments amounted to 13.18 mg g−1 fresh weight and the light stimulated the synthesis of these pigments by isolated roots. Total yellow pigments of 24.12, 38.91 and 46.38 mg g−1 fresh weight was produced by the roots treated with 9, 13.5 and 18% (v/v) gas oil, respectively, representing high values of production. The pigments were released in large quantities in the medium. The increased synthesis of pigments as a result of gas oil treatment was accompanied by a reduction of the peroxidase activity of roots. Given the high production of yellow pigments, systems of isolated root culture could be considered for the study of a larger scale production of safflower pigments widely used for various industrial purposes. 相似文献
426.
Fish processing generates large amounts of solid and liquid wastes. Many different by-products have been produced from fish
processing wastes. Studies on solubilization of Bolti fish (Tilapia nilotica) viscera by endogenous enzymes at different pHs are described. Hydrolysis reactions were conducted with freshly thawed viscera
utilizing an initial temperature gradient and terminated at various time points by heat inactivation of the enzymes. Various
peptones obtained from hydrolysed visceral homogenates of Bolti fish residues showed their suitability for promoting the growth
of lactic acid bacteria (mainly Lactobacillus sake Lb 706), microorganisms with particularly complex nutritional requirements especially peptidic sources. The assay of several
treatments with L. sakei Lb 706, producer of the bacteriocin sakacin A, demonstrated that optimum conditions for biomass and bacteriocin production
only imply a brief autohydrolysis at room temperature. The results showed that the Bolti fish hydrolysates gave remarkable
results to those found in costly commercial media, specifically recommended for culturing and large-scale production of lactic
acid bacteria. 相似文献
427.
AbstractThe purpose of this study was to assess the environmental risk of Balarood Dam in Iran at constructional phase. The scientific methods used in this research were the Environmental Failure Mode and Effects Analysis (EFMEA) and VIKOR. In the process of environmental risk assessment, the EFMEA method was used first to calculate the risk priority number (RPN) for each environmental aspect. The identified risks were ranked based on RPN values in the next stage. Comparison of the RPN values showed that the risk of pollution of Balarood River, with a RPN of 125, is in the first priority. In addition, the environmental risks, identified during the follow-up phase, were weighted by entropy method based on severity, occurrence probability, and extent of pollution.Then, the VIKOR method, as one of the multicriteria decision-making (MCDM) methods, was run to evaluate and prioritize the potential environmental risks. The risk of water pollution under high, medium and low conditions, with a weight of 1,300, 1,000 and 700, was identified as the most important risk of dam construction. Accordingly, the most important corrective action, proposed to mitigate the high priority environmental risks, is to prevent the discharge of sanitary and industrial wastewater into the river. 相似文献
428.
Sajid Rashid Nousheen Bibi Zahida Parveen Shagufta Shafique 《Journal of biomolecular structure & dynamics》2013,31(11):2368-2379
Janus kinases (JAKs) belong to a crucial family of tyrosine kinases, implicated in the patho-physiology of multiple cancer types, and serve as striking therapeutic targets. To date, many potent, either ATP-competitive (PTK domain) or non-ATP-competitive JAK inhibitors have been identified. Among them, Tyrphostin AG-490 (2-cyano-3-(3,4-dihydroxyphenyl)-N-(phenylmethyl)-2-propenamide) is a well-known ATP-competitive inhibitor. However, its mode of action, details of interacting residues, and induced conformational changes in JAK-specific binding sites remain elusive. Here, through comparative structure analysis, molecular docking, and molecular dynamics simulation assays, we explored comparative binding patterns of AG-490 against JAK1, JAK2, and JAK3. Our results entail noteworthy observations about the binding affinity of AG-490 by illustrating distinctive amino acid residues lying at the conserved ATP-binding domains of JAK family members. By subsequent assessment of their structural homology and conserved structural folds, we highlight intriguing prospects to design more specific and potent inhibitors for selective targeting of JAK family members. Our comparative study provides a platform for the rational design of precise and potent inhibitor for selective targeting of JAK family members. 相似文献
429.
The purpose of this research was to mask the intensely bitter taste of ondansetron HCl and to formulate a rapiddisintegrating
tablet (RDT) of the taste-maske drug. Taste masking was done by complexing ondansetron HCl with aminoalkyl methacrylate copolymer
(Eudragit EPO) in different ratios by the precipitation method. Drug-polymer complexes (DPCs) were tested for drug content,
in vitro taste in simulated salivary fluid (SSF) of pH 6.2, and molecular property. Complex that did not release drug in SSF
was considered taste-masked and selected for formulation RDTs. The complex with drug-polymer ratio of 8∶2 did not show drug
release in SSF; therefore, it was selected. The properties of tablets such as tensile strength, wetting time, water absorption
ratio, in vitro disintegration time, and disintegration in the oral cavity were investigated to elucidate the wetting and
disintegration characteristics of tablets. Polyplasdone XL-10 7% wt/wt gave the minimum disintegration time. Tablets of batch
F4 containing spray-dried mannitol and microcrystalline cellulose in the ratio 1∶1 and 7% wt/wt Polyplasdone XL-10 showed
faster disintegration, within 12.5 seconds, than the marketed tablet (112 seconds). Good correlation between in vitro disintegration
behavior and in the oral cavity was recognized. Taste evaluation of RDT in human volunteers revealed considerable taste masking
with the degree of bitterness below threshold value (0.5) ultimately reaching to 0 within 15 minutes, whereas ondansetron
HCl was rated intensely bitter with a score of 3 for 10 minutes. Tablets of batch F4 also revealed rapid drug release (t90, 60 seconds) in SGF compared with marketed formulation (t90, 240 seconds;P<.01). Thus, results conclusively demonstrated successful masking of taste and rapid disintegration of the formulated tablets
in the oral cavity.
Published: June 22, 2007 相似文献
430.
Abdallah Hoda Y. Fareed Ahmed Abdelmaogood Asmaa K. K. Allam Sahar Abdelgawad Mai Deen Loaa A. Tag El 《Molecular diagnosis & therapy》2023,27(2):243-259
Molecular Diagnosis & Therapy - Atherosclerotic plaque is considered the hallmark of atherosclerotic lesions in coronary atherosclerosis (CAS), the primary pathogenesis in coronary artery... 相似文献