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131.
Lisa R. Goldberg Emily J. Yao Julia C. Kelliher Eric R. Reed Jiayi Wu Cox Cory Parks Stacey L. Kirkpatrick Jacob A. Beierle Melanie M. Chen William E. Johnson Gregg E. Homanics Robert W. Williams Camron D. Bryant Megan K. Mulligan 《Genes, Brain & Behavior》2021,20(8):e12774
Psychostimulant (methamphetamine, cocaine) use disorders have a genetic component that remains mostly unknown. We conducted genome-wide quantitative trait locus (QTL) analysis of methamphetamine stimulant sensitivity. To facilitate gene identification, we employed a Reduced Complexity Cross between closely related C57BL/6 mouse substrains and examined maximum speed and distance traveled over 30 min following methamphetamine (2 mg/kg, i.p.). For maximum methamphetamine-induced speed following the second and third administration, we identified a single genome-wide significant QTL on chromosome 11 that peaked near the Cyfip2 locus (LOD = 3.5, 4.2; peak = 21 cM [36 Mb]). For methamphetamine-induced distance traveled following the first and second administration, we identified a genome-wide significant QTL on chromosome 5 that peaked near a functional intronic indel in Gabra2 coding for the alpha-2 subunit of the GABA-A receptor (LOD = 3.6–5.2; peak = 34–35 cM [66–67 Mb]). Striatal cis-expression QTL mapping corroborated Gabra2 as a functional candidate gene underlying methamphetamine-induced distance traveled. CRISPR/Cas9-mediated correction of the mutant intronic deletion on the C57BL/6J background to the wild-type C57BL/6NJ allele was sufficient to reduce methamphetamine-induced locomotor activity toward the wild-type C57BL/6NJ-like level, thus validating the quantitative trait variant (QTV). These studies show the power and efficiency of Reduced Complexity Crosses in identifying causal variants underlying complex traits. Functionally restoring Gabra2 expression decreased methamphetamine stimulant sensitivity and supports preclinical and human genetic studies implicating the GABA-A receptor in psychostimulant addiction-relevant traits. Importantly, our findings have major implications for studying psychostimulants in the C57BL/6J strain—the gold standard strain in biomedical research. 相似文献
132.
Exotic perennial grasses (EPGs) pose a significant risk to native communities globally. With over 2,200 species in Australia, understanding which characteristics enable high threat invasions, and comparing between functionally similar EPGs, can help prioritise species management. We developed a framework of risk and used the literature to rank 21 EPGs considered a threat to plant communities in New South Wales, while also evaluating the reliability of information currently available. Characteristics were scored within five broad categories that distinguish invasiveness: Arrival, Establishment, Persistence, Impact and Distribution. These included aspects of reproductive biology, competitive ability and environmental tolerance. The risk assessment was effective in assessing key characteristics of invasion. EPGs with an economic benefit (trade‐off species) were more likely to have reliable research and frequently ranked as high‐risk invaders in natural habitats due to the overlap of characteristics important in invasion with those considered important in agriculture. Lack of formal scientific research hindered assessment for some species, and some traits had been poorly assessed in the literature. High uncertainty was associated with key characteristics for Establishment, Persistence and Impact. Uncertainty in key characteristics revealed a need for improved integration of less formal research validated by more formal scientific research. This may lead to more informed decisions in the management of EPGs in native habitats and assist in early control of EPGs not yet assessed. 相似文献
133.
Phytochemistry Reviews - COVID-19, the highly contagious novel disease caused by SARS-CoV-2, has become a major international concern as it has spread quickly all over the globe. However,... 相似文献
134.
María Eugenia Cabral Lucía I.C. Figueroa Julia I. Fariña 《Revista iberoamericana de micología》2013,30(1):31-38
BackgroundFrequent opportunist fungal infections and the resistance to available antifungal drugs promoted the development of new alternatives for treatment, like antifungal drug combinations.AimsThis work aimed to detect the antifungal synergism between statins and azoles by means of an agar-well diffusion bioassay with Saccharomyces cerevisiae ATCC 32051 and Candida utilis Pr1–2 as test strains.MethodsSynergistic antifungal effects were tested by simultaneously adding a sub inhibitory concentration (SIC) of statin (atorvastatin, lovastatin, pravastatin, rosuvastatin or simvastatin) plus a minimal inhibitory concentration (MIC) of azole (clotrimazole, fluconazole, itraconazole, ketoconazole or miconazole) to yeast-embedded YNB agar plates, and a positive result corresponded to a yeast growth inhibition halo higher than that produced by the MIC of the azole alone. Yeast cell ergosterol quantification by RP-HPLC was used to confirm statin–azole synergism, and ergosterol rescue bioassays were performed for evaluating statin-induced ergosterol synthesis blockage.ResultsGrowth inhibition was significantly increased when clotrimazole, fluconazole, itraconazole, ketoconazole and miconazole were combined with atorvastatin, lovastatin, rosuvastatin and simvastatin. Highest growth inhibition increments were observed on S. cerevisiae (77.5%) and C. utilis (43.2%) with a SIC of simvastatin plus a MIC of miconazole, i.e. 4 + 2.4 μg/ml or 20 + 4.8 μg/ml, respectively. Pravastatin showed almost no significant effects (0–7.6% inhibition increase). Highest interaction ratios between antifungal agents corresponded to simvastatin–miconazole combinations and were indicative of synergism. Synergism was also confirmed by the increased reduction in cellular ergosterol levels (S. cerevisiae, 40% and C. utilis, 22%). Statin-induced ergosterol synthesis blockage was corroborated by means of ergosterol rescue bioassays, pravastatin being the most easily abolished inhibition whilst rosuvastatin being the most ergosterol-refractory.ConclusionsSelected statin–azole combinations might be viable alternatives for the therapeutic management of mycosis at lower administration doses or with a higher efficiency. 相似文献
135.
Jie Ni Paul Cozzi Jingli Hao Julia Beretov Lei Chang Wei Duan Sarah Shigdar Warick Delprado Peter Graham Joseph Bucci John Kearsley Yong Li 《The international journal of biochemistry & cell biology》2013,45(12):2736-2748
Prostate cancer (CaP) is the second leading malignancy in men. The role of epithelial cell adhesion molecule (EpCAM), also known as CD326, in CaP progression and therapeutic resistance is still uncertain. Here, we aimed to investigate the roles of EpCAM in CaP metastasis and chemo/radioresistance. Expression of EpCAM in CaP cell lines and human CaP tissues was assessed using immunofluorescence and immunohistochemistry, respectively. EpCAM was knocked down (KD) in PC-3, DU145 and LNCaP-C4-2B cells using small interfering RNA (siRNA), and KD results were confirmed by confocal microscope, Western blotting and quantitative real time polymerase chain reaction (qRT-PCR). Cell growth was evaluated by proliferation and colony formation assays. The invasive potential was assessed using a matrigel chamber assay. Tumorigenesis potential was measured by a sphere formation assay. Chemo-/radiosensitivity were measured using a colony formation assay. Over-expression of EpCAM was found in primary CaP tissues and lymph node metastases including cancer cells and surrounding stromal cells. KD of EpCAM suppressed CaP proliferation and invasive ability, reduced sphere formation, enhanced chemo-/radiosensitivity, and down-regulated E-cadherin, p-Akt, p-mTOR, p-4EBP1 and p-S6K expression in CaP cells. Our findings suggest that EpCAM plays an important role in CaP proliferation, invasion, metastasis and chemo-/radioresistance associated with the activation of the PI3K/Akt/mTOR signaling pathway and is a novel therapeutic target to sensitize CaP cells to chemo-/radiotherapy. 相似文献
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138.
Monika Dybicz Anna Gierczak Julia Dąbrowska Łukasz Rdzanek Bogdan Michałowicz 《Parasitology international》2013,62(4):364-367
The identity of the causative agent of cystic echinococcosis (CE) in humans from central Poland receiving treatment between 2000 and 2010 was determined. A total of 47 samples obtained after hepatectomy were examined and protoscoleces were identified in wet preparations in 27 cases. Using DNA extracted from the samples, two mitochondrial regions (nad1 and cox1 genes) were amplified and the nad1 fragment was sequenced. This PCR analysis confirmed the presence of Echinococcus species in 30 cases and nad1 sequence alignments showed identity with the G7 (pig) strain, Echinococcus canadensis. These data demonstrate that the pig strain of this parasite is the most frequent causative agent of human cystic echinococcosis in central Poland. 相似文献
139.
Julia Pawłowska Grit Walther Mateusz Wilk Sybren de Hoog Marta Wrzosek 《Organisms Diversity & Evolution》2013,13(4):497-502
Compensatory base changes (CBCs) in helix II of rDNA ITS2, suggested as a molecular classifier for fungi, were analyzed in Mucor circinelloides and its varieties. Only a few CBCs were found in the complex. Three out of the four accepted formae (f. circinelloides, f. lusitanicus, f. janssenii) did not exhibit CBCs. One CBC was found between strains that form zygospores; consequently, CBC is not always concordant with mating experiments. Strains with two CBC are unable to breed. It is suggested that some strains of the M. circinelloides complex are at the beginning of speciation. 相似文献
140.
Albert Flexas Jaume Rosselló Julia F. Christensen Marcos Nadal Antonio Olivera La Rosa Enric Munar 《PloS one》2013,8(11)
We examined the influence of affective priming on the appreciation of abstract artworks using an evaluative priming task. Facial primes (showing happiness, disgust or no emotion) were presented under brief (Stimulus Onset Asynchrony, SOA = 20ms) and extended (SOA = 300ms) conditions. Differences in aesthetic liking for abstract paintings depending on the emotion expressed in the preceding primes provided a measure of the priming effect. The results showed that, for the extended SOA, artworks were liked more when preceded by happiness primes and less when preceded by disgust primes. Facial expressions of happiness, though not of disgust, exerted similar effects in the brief SOA condition. Subjective measures and a forced-choice task revealed no evidence of prime awareness in the suboptimal condition. Our results are congruent with findings showing that the affective transfer elicited by priming biases evaluative judgments, extending previous research to the domain of aesthetic appreciation. 相似文献