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41.
42.
Brendan B. Larsen Lennie Chen Brandon S. Maust Moon Kim Hong Zhao Wenjie Deng Dylan Westfall Ingrid Beck Lisa M. Frenkel James I. Mullins 《PloS one》2013,8(10)
454 pyrosequencing, a massively parallel sequencing (MPS) technology, is often used to study HIV genetic variation. However, the substantial mismatch error rate of the PCR required to prepare HIV-containing samples for pyrosequencing has limited the detection of rare variants within viral populations to those present above ~1%. To improve detection of rare variants, we varied PCR enzymes and conditions to identify those that combined high sensitivity with a low error rate. Substitution errors were found to vary up to 3-fold between the different enzymes tested. The sensitivity of each enzyme, which impacts the number of templates amplified for pyrosequencing, was shown to vary, although not consistently across genes and different samples. We also describe an amplicon-based method to improve the consistency of read coverage over stretches of the HIV-1 genome. Twenty-two primers were designed to amplify 11 overlapping amplicons in the HIV-1 clade B gag-pol and env gp120 coding regions to encompass 4.7 kb of the viral genome per sample at sensitivities as low as 0.01-0.2%. 相似文献
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44.
Recently the metabolic cost of swinging the limbs has been found to be much greater than previously thought, raising the possibility that limb rotational inertia influences the energetics of locomotion. Larger mammals have a lower mass-specific cost of transport than smaller mammals. The scaling of the mass-specific cost of transport is partly explained by decreasing stride frequency with increasing body size; however, it is unknown if limb rotational inertia also influences the mass-specific cost of transport. Limb length and inertial properties – limb mass, center of mass (COM) position, moment of inertia, radius of gyration, and natural frequency – were measured in 44 species of terrestrial mammals, spanning eight taxonomic orders. Limb length increases disproportionately with body mass via positive allometry (length ∝ body mass0.40); the positive allometry of limb length may help explain the scaling of the metabolic cost of transport. When scaled against body mass, forelimb inertial properties, apart from mass, scale with positive allometry. Fore- and hindlimb mass scale according to geometric similarity (limb mass ∝ body mass1.0), as do the remaining hindlimb inertial properties. The positive allometry of limb length is largely the result of absolute differences in limb inertial properties between mammalian subgroups. Though likely detrimental to locomotor costs in large mammals, scale effects in limb inertial properties appear to be concomitant with scale effects in sensorimotor control and locomotor ability in terrestrial mammals. Across mammals, the forelimb''s potential for angular acceleration scales according to geometric similarity, whereas the hindlimb''s potential for angular acceleration scales with positive allometry. 相似文献
45.
Giuseppe Tortoriello Brandon P. Rhodes Sara M. Takacs Jordyn M. Stuart Arjun Basnet Siham Raboune Theodore S. Widlanski Patrick Doherty Tibor Harkany Heather B. Bradshaw 《PloS one》2013,8(7)
Lipid metabolism is critical to coordinate organ development and physiology in response to tissue-autonomous signals and environmental cues. Changes to the availability and signaling of lipid mediators can limit competitiveness, adaptation to environmental stressors, and augment pathological processes. Two classes of lipids, the N-acyl amides and the 2-acyl glycerols, have emerged as important signaling molecules in a wide range of species with important signaling properties, though most of what is known about their cellular functions is from mammalian models. Therefore, expanding available knowledge on the repertoire of these lipids in invertebrates will provide additional avenues of research aimed at elucidating biosynthetic, metabolic, and signaling properties of these molecules. Drosophila melanogaster is a commonly used organism to study intercellular communication, including the functions of bioactive lipids. However, limited information is available on the molecular identity of lipids with putative biological activities in Drosophila. Here, we used a targeted lipidomics approach to identify putative signaling lipids in third instar Drosophila larvae, possessing particularly large lipid mass in their fat body. We identified 2-linoleoyl glycerol, 2-oleoyl glycerol, and 45 N-acyl amides in larval tissues, and validated our findings by the comparative analysis of Oregon-RS, Canton-S and w1118 strains. Data here suggest that Drosophila represent another model system to use for the study of 2-acyl glycerol and N-acyl amide signaling. 相似文献
46.
Andrea G. Marshall Jennifer A. Watson Jada J. Hallengren Brandon J. Walters Lynn E. Dobrunz Ludwig Francillon Julie A. Wilson Scott E. Phillips Scott M. Wilson 《PloS one》2013,8(12)
In this study, we identified and characterized an N-ethyl-N-nitrosourea (ENU) induced mutation in Usp14 (nmf375) that leads to adult-onset neurological disease. The nmf375 mutation causes aberrant splicing of Usp14 mRNA, resulting in a 95% reduction in USP14. We previously showed that loss of USP14 in ataxia (ax
J) mice results in reduced ubiquitin levels, motor endplate disease, Purkinje cell axonal dystrophy and decreased hippocampal paired pulse facilitation (PPF) during the first 4-6 weeks of life, and early postnatal lethality by two months of age. Although the loss of USP14 is comparable between the nmf375 and ax
J mice, the nmf375 mice did not exhibit these ax
J developmental abnormalities. However, by 12 weeks of age the nmf375 mutants present with ubiquitin depletion and motor endplate disease, indicating a continual role for USP14-mediated regulation of ubiquitin pools and neuromuscular junction (NMJ) structure in adult mice. The observation that motor endplate disease was only seen after ubiquitin depletion suggests that the preservation of NMJ structure requires the stable maintenance of synaptic ubiquitin pools. Differences in genetic background were shown to affect ubiquitin expression and dramatically alter the phenotypes caused by USP14 deficiency. 相似文献
47.
Brandon Faubert Gino Boily Said Izreig Takla Griss Bozena Samborska Zhifeng Dong Fanny Dupuy Christopher Chambers Benjamin J. Fuerth Benoit Viollet Orval A. Mamer Daina Avizonis Ralph J. DeBerardinis Peter M. Siegel Russell G. Jones 《Cell metabolism》2013,17(1):113-124
Highlights? Loss of AMPKα1 cooperates with the Myc oncogene to accelerate lymphomagenesis ? AMPKα dysfunction enhances aerobic glycolysis (Warburg effect) ? Inhibiting HIF-1α reverses the metabolic effects of AMPKα loss ? HIF-1α mediates the growth advantage of tumors with reduced AMPK signaling 相似文献
48.
Allison D. Ebert Brandon C. Shelley Amanda M. Hurley Marco Onorati Valentina Castiglioni Teresa N. Patitucci Soshana P. Svendsen Virginia B. Mattis Jered V. McGivern Andrew J. Schwab Dhruv Sareen Ho Won Kim Elena Cattaneo Clive N. Svendsen 《Stem cell research》2013,10(3):417-427
We have developed a simple method to generate and expand multipotent, self-renewing pre-rosette neural stem cells from both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (iPSCs) without utilizing embryoid body formation, manual selection techniques, or complex combinations of small molecules. Human ESC and iPSC colonies were lifted and placed in a neural stem cell medium containing high concentrations of EGF and FGF-2. Cell aggregates (termed EZ spheres) could be expanded for long periods using a chopping method that maintained cell–cell contact. Early passage EZ spheres rapidly down-regulated OCT4 and up-regulated SOX2 and nestin expression. They retained the potential to form neural rosettes and consistently differentiated into a range of central and peripheral neural lineages. Thus, they represent a very early neural stem cell with greater differentiation flexibility than other previously described methods. As such, they will be useful for the rapidly expanding field of neurological development and disease modeling, high-content screening, and regenerative therapies based on pluripotent stem cell technology. 相似文献
49.
Jessica L. Miller Sara Murray Ashley M. Vaughan Anke Harupa Brandon Sack Michael Baldwin Ian N. Crispe Stefan H. I. Kappe 《PloS one》2013,8(4)
The liver stages of Plasmodium parasites are important targets for the development of anti-malarial vaccine candidates and chemoprophylaxis approaches that aim to prevent clinical infection. Analyzing the impact of interventions on liver stages in the murine malaria model system Plasmodium yoelii has been cumbersome and requires terminal procedures. In vivo imaging of bioluminescent parasites has previously been shown to be an effective and non-invasive alternative to monitoring liver stage burden in the Plasmodium berghei model. Here we report the generation and characterization of a transgenic P. yoelii parasite expressing the reporter protein luciferase throughout the parasite life cycle. In vivo bioluminescent imaging of these parasites allows for quantitative analysis of P. yoelii liver stage burden and parasite development, which is comparable to quantitative RT-PCR analysis of liver infection. Using this system, we show that both BALB/cJ and C57BL/6 mice show comparable susceptibility to P. yoelii infection with sporozoites and that bioluminescent imaging can be used to monitor protective efficacy of attenuated parasite immunizations. Thus, this rapid, simple and noninvasive method for monitoring P. yoelii infection in the liver provides an efficient system to screen and evaluate the effects of anti-malarial interventions in vivo and in real-time. 相似文献
50.
Stephanie Melkonian Maria Argos Megan N. Hall Yu Chen Faruque Parvez Brandon Pierce Hongyuan Cao Briseis Aschebrook-Kilfoy Alauddin Ahmed Tariqul Islam Vesna Slavcovich Mary Gamble Parvez I. Haris Joseph H. Graziano Habibul Ahsan 《PloS one》2013,8(11)