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- Barclay, C J, et al.
(författare)
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Initial mechanical efficiency of isolated cardiac muscle
- 2003
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Ingår i: Journal of Experimental Biology. - 0022-0949 .- 1477-9145. ; 206:Pt 16, s. 2725-32
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to determine whether the initial mechanical efficiency (ratio of work output to initial metabolic cost) of isolated cardiac muscle is over 60%, as has been reported previously, or whether it is approximately 30%, as suggested by an estimate based on the well-established net mechanical efficiency (ratio of work output to total, suprabasal energy cost) of 15%. Determination of initial efficiency required separation of the enthalpy output (i.e. heat + work) into initial and recovery components. The former corresponds to energy produced by reactions that use high-energy phosphates and the latter to energy produced in the regeneration of high-energy phosphates. The two components were separated mathematically. Experiments were performed in vitro (30 degrees C) using preparations dissected from rat left ventricular papillary muscles (N=13). Muscle work output and heat production were measured during a series of 40 contractions using a contraction protocol designed to mimic in vivo papillary muscle activity. Net mechanical efficiency was 13.3+/-0.7%. The total enthalpy output was 2.16 times greater than the initial enthalpy output, so that initial mechanical efficiency was 28.1+/-1.2%.
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- Patro, SC, et al.
(författare)
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Combined HIV-1 sequence and integration site analysis informs viral dynamics and allows reconstruction of replicating viral ancestors
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 116:51, s. 25891-25899
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Tidskriftsartikel (refereegranskat)abstract
- Understanding HIV-1 persistence despite antiretroviral therapy (ART) is of paramount importance. Both single-genome sequencing (SGS) and integration site analysis (ISA) provide useful information regarding the structure of persistent HIV DNA populations; however, until recently, there was no way to link integration sites to their cognate proviral sequences. Here, we used multiple-displacement amplification (MDA) of cellular DNA diluted to a proviral endpoint to obtain full-length proviral sequences and their corresponding sites of integration. We applied this method to lymph node and peripheral blood mononuclear cells from 5 ART-treated donors to determine whether groups of identical subgenomic sequences in the 2 compartments are the result of clonal expansion of infected cells or a viral genetic bottleneck. We found that identical proviral sequences can result from both cellular expansion and viral genetic bottlenecks occurring prior to ART initiation and following ART failure. We identified an expanded T cell clone carrying an intact provirus that matched a variant previously detected by viral outgrowth assays and expanded clones with wild-type and drug-resistant defective proviruses. We also found 2 clones from 1 donor that carried identical proviruses except for nonoverlapping deletions, from which we could infer the sequence of the intact parental virus. Thus, MDA-SGS can be used for “viral reconstruction” to better understand intrapatient HIV-1 evolution and to determine the clonality and structure of proviruses within expanded clones, including those with drug-resistant mutations. Importantly, we demonstrate that identical sequences observed by standard SGS are not always sufficient to establish proviral clonality.
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