22 research outputs found
Highly efficient small interfering RNA delivery to primary mammalian neurons induces MicroRNA-like effects before mRNA degradation
The study of protein function in neurons has been hindered by the lack of highly efficient, nontoxic methods of inducing RNA interference in such cells. Here we show that application of synthetic small interfering RNA( siRNA) linked to the vector peptide Penetratin1 results in rapid, highly efficient uptake of siRNA by entire populations of cultured primary mammalian hippocampal and sympathetic neurons. This treatment leads to specific knock-down of targeted proteins within hours without the toxicity associated with transfection. In contrast to current methods, our technique permits study of protein function across entire populations with minimal disturbance of complex cellular networks. Using this technique, we found that protein knock-down ( evident after 6 hr) precedes any decrease in targeted message ( evident after 24 hr), suggesting an early, translational repression by perfectly targeted siRNAs.PT: J; CR: BARTEL DP, 2004, CELL, V116, P281 BERTRAND E, 2001, MOL CELL NEUROSCI, V18, P503 DEROSSI D, 1994, J BIOL CHEM, V269, P10444 DOENCH JG, 2003, GENE DEV, V17, P438 DOSTIE JE, 2003, RNA, V9, P180 ELBASHIR SM, 2001, EMBO J, V20, P6877 FINK CC, 2003, NEURON, V39, P283 FIRE A, 1998, NATURE, V391, P806 GAUDILLIERE B, 2002, J BIOL CHEM, V277, P46442 HANNON GJ, 2002, NATURE, V418, P244 HUTVAGNER G, 2002, SCIENCE, V297, P2056 JOHNSTON RJ, 2003, NATURE, V426, P845 JOLIOT A, 2004, NAT CELL BIOL, V6, P189 KHVOROVA A, 2003, CELL, V115, P209 KIM J, 2004, P NATL ACAD SCI USA, V101, P360 KRICHEVSKY AM, 2002, P NATL ACAD SCI USA, V99, P11926 KRICHEVSKY AM, 2003, RNA, V9, P1274 LAI EC, 2003, CURR BIOL, V13, R925 LLAVE C, 2002, SCIENCE, V297, P2053 MURATOVSKA A, 2004, FEBS LETT, V558, P63 OMI K, 2004, FEBS LETT, V558, P89 RABACCHI SA, 2004, NEUROBIOL AGING, V25, P1057 REYNOLDS A, 2004, NAT BIOTECHNOL, V22, P326 SAXENA S, 2003, J BIOL CHEM, V278, P44312 SCHERER LJ, 2003, NAT BIOTECHNOL, V21, P1457 SCHWARZ DS, 2003, CELL, V115, P199 THEODORE L, 1995, J NEUROSCI, V15, P7158 TOROCSIK B, 2002, J NEUROSCI, V22, P8971 TROY CM, 1994, P NATL ACAD SCI USA, V91, P6384 TROY CM, 1996, J NEUROSCI, V16, P253 TROY CM, 1996, P NATL ACAD SCI USA, V93, P5635 TROY CM, 2001, J NEUROSCI, V21, P5007 TROY CM, 2002, J BIOL CHEM, V277, P34295 VICKERS TA, 2003, J BIOL CHEM, V278, P7108 ZENG Y, 2003, P NATL ACAD SCI USA, V100, P9779; NR: 35; TC: 22; J9: J NEUROSCI; PG: 7; GA: 869ZASource type: Electronic(1
Global Call to Action: maximize the public health impact of intermittent preventive treatment of malaria in pregnancy in sub-Saharan Africa.
Intermittent preventive treatment of malaria in pregnancy is a highly cost-effective intervention which significantly improves maternal and birth outcomes among mothers and their newborns who live in areas of moderate to high malaria transmission. However, coverage in sub-Saharan Africa remains unacceptably low, calling for urgent action to increase uptake dramatically and maximize its public health impact. The 'Global Call to Action' outlines priority actions that will pave the way to success in achieving national and international coverage targets. Immediate action is needed from national health institutions in malaria-endemic countries, the donor community, the research community, members of the pharmaceutical industry and private sector, along with technical partners at the global and local levels, to protect pregnant women and their babies from the preventable, adverse effects of malaria in pregnancy
The safety of artemisinins during pregnancy: a pressing question.
BACKGROUND: An increasing number of countries in sub-Saharan Africa are changing to artemisinins combination therapy (ACT) as first or second line treatment for malaria. There is an urgent need to assess the safety of these drugs in pregnant women who may be inadvertently exposed to or actively treated with ACTs. OBJECTIVES: To examine existing published evidence on the relationship between artemisinin compounds and adverse pregnancy outcomes and consider the published evidence with regard to the safety of these compounds when administered during pregnancy. METHODS: Studies on ACT use in pregnancy were identified via searches of MEDLINE, EMBASE, Cochrane and Current Contents databases. Data on study characteristics, maternal adverse events, pregnancy outcomes and infant follow up were extracted. RESULTS: Fourteen relevant studies (nine descriptive/case reports and five controlled trials) were identified. Numbers of participants in these studies ranged from six to 461. Overall there were reports on 945 women exposed to an artemisinin during pregnancy, 123 in the 1st trimester and 822 in 2nd or 3rd trimesters. The primary end points for these studies were drug efficacy and parasite clearance. Secondary endpoints were birth outcomes including low birth weight, pre-term birth, pregnancy loss, congenital anomalies and developmental milestones. While none of the studies found evidence for an association between the use of artemisinin compounds and increased risk of adverse pregnancy outcomes, none were of sufficient size to detect small differences in event rates that could be of public health importance. Heterogeneity between studies in the artemisinin and comparator drugs used, and in definitions of adverse pregnancy outcomes, limited any pooled analysis. CONCLUSION: The limited data available suggest that artemisinins are effective and unlikely to be cause of foetal loss or abnormalities, when used in late pregnancy. However, none of these studies had adequate power to rule out rare serious adverse events, even in 2nd and 3rd trimesters and there is not enough evidence to effectively assess the risk-benefit profile of artemisinin compounds for pregnant women particularly for 1st trimester exposure. Methodologically rigorous, larger studies and post-marketing pharmacovigilance are urgently required
Systematic review: Impact of meningococcal vaccination on pharyngeal carriage of meningococci.
OBJECTIVE: To investigate the effect of meningococcal vaccines on pharyngeal carriage of meningococci. METHODS: Systematic review. MEDLINE and EMBASE were searched for relevant studies. Controlled trials and observational studies which used comparison groups or compared carriage rates before and after vaccination were included in the review. RESULTS: Twenty-nine studies satisfied the inclusion criteria. Twenty-five studies reported the effect of a polysaccharide vaccine, one the effect of a serogroup C conjugate vaccine and three the impact of serogroup B outer-membrane vaccines on overall and/or serogroup-specific meningococcal carriage rates. Ten studies of meningococcal polysaccharide vaccines found reduced serogroup-specific carriage; seven of these focussed on high-risk groups and had a short follow-up period. Only one of five studies of civilian populations in Africa showed a significantly reduced carriage. Many studies had methodological shortcomings. The one study which assessed the effect of a meningococcal conjugate vaccine on carriage showed a significant impact. Three studies of serogroup B outer-membrane protein vaccines showed no effect on carriage. CONCLUSIONS: A few well-designed trials of the impact of meningococcal vaccines on carriage have been undertaken. Such studies should be an essential component of the evaluation of new meningococcal vaccines, particularly those introduced to control epidemic meningococcal disease in Africa
Genetic variation in heat tolerance-related traits in a population of wheat multiple synthetic derivatives
Durum Wheat Field Performance and Stability in the Irrigated, Dry and Heat-Prone Environments of Sudan
Developing climate-resilient crop varieties with better performance under variable environments is essential to ensure food security in a changing climate. This process is significantly influenced, among other factors, by genotype × environment (G × E) interactions. With the objective of identifying high-yielding and stable genotypes, 20 elite durum wheat lines were evaluated in 24 environments (location–season combination) during 5 crop seasons (2010/11–2014/15). The REML (residual maximum likelihood)-predicted means of grain yield of 16 genotypes that were common across all environments ranged from 3522 kg/ha in G201 to 4132 kg/ha in G217. Results of additive main effect and multiplicative interaction (AMMI) analysis showed that genotypes (G), environments (E), and genotype × environment interaction (GEI) significantly affected grain yield. From the total sum of squares due to treatments (G + E + GEI), E attributed the highest proportion of the variation (90.0%), followed by GEI (8.7%) and G (1.3%). Based on the first four AMMI selections for grain yield in the 24 environments, genotypes G217, G219, G211, and G213 were selected in 23, 12, 11, and 9 environments, respectively. The genotype and genotype × environment biplot (GGE) biplot polygon view showed that the environments were separated into three mega-environments. The winning genotypes in these mega-environments were G217, G214, and G204. Genotypes G212, G220, G217, G215, and G213 showed low AMMI stability values (ASV), whereas genotypes G217, G220, G212, G211, and G219 showed low genotype selection index (GSI), indicating their better stability and adaptability to the test environments. The results indicated that genotypes G217, G219, G211, G213, and G220 combined both high grain yield and stability/adaptability under dry but irrigated and heat-prone environments. An in-depth analysis of the superior genotypes could help better understand the stress-adaptive traits that could be targeted to further increase durum wheat yield and stability under the changing climate
Common computed tomography artifact: source and avoidance
Abstract Background Artifacts have significantly degraded the quality of computed tomography (CT) images, to the extent of making them unusable for diagnosis. The types of artifact that could be used are as follows: (a) streaking, which is commonly due to a discrepancy in a single measurement, (b) shading, which is due to a group of channels deviating gradually from the true measurement, (c) rings, which are due to errors in individual detector calibration and (d) distortion, which is due to helical reconstruction. It is occasionally possible to avoid scanning of a bony area, by means of changing the postion of the patient. Thus, this study aimed to evaluate the common artifacts that affect image quality and the method of correction to improve image quality. Results The data were collected by distributing a questionnaire to the CT technologist at different hospitals about the most common type of artifacts in the CT images, source of artifacts and methods of correction. A total of 95 CT technologists responded to the questionnaire, which included 67% males and 33% females. Most of the participants (70%) were experienced CT technologists, and 61% of the participants had not done any subspecialty CT scan courses. The most common artifact used in the CT departments was motion artifact in brain CT (73%), and the best method to reduce motion artifact was patient preparation (87%). Conclusions The most common shown artifact in this study was motion artifact, and the common cause was the patient-based artifact. It is important to understand why objects occur and how they could be prevented or suppressed to improve image quality
Predicting Green Water Footprint of Sugarcane Crop Using Multi-Source Data-Based and Hybrid Machine Learning Algorithms in White Nile State, Sudan
Water scarcity and climate change present substantial obstacles for Sudan, resulting in extensive migration. This study seeks to evaluate the effectiveness of machine learning models in forecasting the green water footprint (GWFP) of sugarcane in the context of climate change. By analyzing various input variables such as climatic conditions, agricultural data, and remote sensing metrics, the research investigates their effects on the sugarcane cultivation period from 2001 to 2020. A total of seven models, including random forest (RF), extreme gradient boosting (XGBoost), and support vector regressor (SVR), in addition to hybrid combinations like RF-XGB, RF-SVR, XGB-SVR, and RF-XGB-SVR, were applied across five scenarios (Sc) which includes different combinations of variables used in the study. The most significant mean bias error (MBE) was recorded in RF with Sc3 (remote sensing parameters), at 5.14 m3 ton−1, followed closely by RF-SVR at 5.05 m3 ton−1, while the minimum MBE was 0.03 m3 ton−1 in RF-SVR with Sc1 (all parameters). SVR exhibited the highest R2 values throughout all scenarios. Notably, the R2 values for dual hybrid models surpassed those of triple hybrid models. The highest Nash–Sutcliffe efficiency (NSE) value of 0.98 was noted in Sc2 (climatic parameters) and XGB-SVR, whereas the lowest NSE of 0.09 was linked to SVR in Sc3. The root mean square error (RMSE) varied across different ML models and scenarios, with Sc3 displaying the weakest performance regarding remote sensing parameters (EVI, NDVI, SAVI, and NDWI). Effective precipitation exerted the most considerable influence on GWFP, contributing 81.67%, followed by relative humidity (RH) at 7.5% and Tmax at 5.24%. The study concludes that individual models were as proficient as, or occasionally surpassed, double and triple hybrid models in predicting GWFP for sugarcane. Moreover, remote sensing indices demonstrated minimal positive influence on GWFP prediction, with Sc3 producing the lowest statistical outcomes across all models. Consequently, the study advocates for the use of hybrid models to mitigate the error term in the prediction of sugarcane GWFP
Influence of combining Al2O3, La2O3, Gd2O3, and Dy2O3with barium borosilicate glass-ceramics: A case study of gamma radiation interaction parameters
The goal of this investigation is to test the barium boro-silicate glass-ceramics with different additives against gamma radiation using the FLUKA Monte Carlo code. On four different glass-ceramics samples, the effect of an equal quantity of Al2O3, La2O3, Gd2O3, and Dy2O3 with barium borosilicate glass-ceramics on the radiation shielding capabilities of the glass-ceramics was investigated. In the examined glass ceramics, densities were obtained to investigate glass samples. The densities obtained were 3.92, 4.432, 4.52, and 4.88 g/cm3, respectively. BBSDy sample has the highest density which indicates that it is more effective for radiation shielding. The shielding parameters have been calculated at 0.356, 0.662, 1.173, and 1.333 MeV. The obtained results have been compared with the NistXCOM web page and Phy-X/PSD platform. The results showed a good agreement between FLUKA code, NistXCOM, and Phy-X/PSD. The calculated shielding parameters increase with additive (Al2O3, La2O3, Gd2O3, and Dy2O3). Moreover, the 50BaO-15SiO2-30B2O3-5Al2O3-5Dy2O3 specimen has the best radiation shielding features among the other glass-ceramics. In conclusion, the BBSDY sample containing 5 mol per cent 5 mol% Dy-III-Oxide would be the most effective in terms of radiation shielding, based on the results obtained in this study. When Dy-III Oxide concentrations were increased, linear and mass attenuation coefficient values were significantly increased, which contributed directly to the development of radiation shielding characteristics in the glass-ceramic. © 2022 The Author(s).Deanship of Scientific Research, University of Jordan, DSR, (DSR-2021-03-03149)This work was funded by the Deanship of Scientific Research at Jouf University under grant No ( DSR-2021-03-03149 )
Ki-67 is a PP1-interacting protein that organises the mitotic chromosome periphery
Copyright @ 2014 Booth et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.When the nucleolus disassembles during open mitosis, many nucleolar proteins and RNAs associate with chromosomes, establishing a perichromosomal compartment coating the chromosome periphery. At present nothing is known about the function of this poorly characterised compartment. In this study, we report that the nucleolar protein Ki-67 is required for the assembly of the perichromosomal compartment in human cells. Ki-67 is a cell-cycle regulated protein phosphatase 1-binding protein that is involved in phospho-regulation of the nucleolar protein B23/nucleophosmin. Following siRNA depletion of Ki-67, NIFK, B23, nucleolin, and four novel chromosome periphery proteins all fail to associate with the periphery of human chromosomes. Correlative light and electron microscopy (CLEM) images suggest a near-complete loss of the entire perichromosomal compartment. Mitotic chromosome condensation and intrinsic structure appear normal in the absence of the perichromosomal compartment but significant differences in nucleolar reassembly and nuclear organisation are observed in post-mitotic cells
