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41.
Economy is a central principle for understanding animal locomotion. Yet, compared with theoretical predictions concerning economy, animals run with compliant legs that are energetically costly. Here, we address this apparent paradox, highlighting two factors that predict benefits for compliant gaits: (i) minimizing cost of work associated with bouncing viscera; and (ii) leg control for robust stability in uneven terrain. We show that consideration of the effects of bouncing viscera predicts an energetic optimum for relatively compliant legs. To compare stability in uneven terrain, we introduce the normalized maximum drop (NMD), a measure based on simple kinematics, which predicts that compliant legs allow negotiation of relatively larger terrain perturbations without failure. Our model also suggests an inherent trade-off in control of leg retraction velocity (ω) for stability: low ω allows higher NMD, reducing fall risk, whereas high ω minimizes peak forces with terrain drops, reducing injury risk. Optimization for one of these factors explicitly limits the other; however, compliant legs relax this trade-off, allowing greater stability by both measures. Our models suggest compromises in leg control for economy and stability that might explain why animals run with compliant legs. 相似文献
42.
Yue Qu Andrew J Daley Taghrid S Istivan Suzanne M Garland Margaret A Deighton 《Annals of clinical microbiology and antimicrobials》2010,9(1):1-12
Background
Coagulase-negative staphylococci are major causes of bloodstream infections in very low birth weight babies cared for in Neonatal Intensive Care Units. The virulence of these bacteria is mainly due to their ability to form biofilms on indwelling medical devices. Biofilm-related infections often fail to respond to antibiotic chemotherapy guided by conventional antibiotic susceptibility tests.Methods
Coagulase-negative staphylococcal blood culture isolates were grown in different phases relevant to biofilm formation: planktonic cells at mid-log phase, planktonic cells at stationary phase, adherent monolayers and mature biofilms and their susceptibilities to conventional antibiotics were assessed. The effects of oxacillin, gentamicin, and vancomycin on preformed biofilms, at the highest achievable serum concentrations were examined. Epifluorescence microscopy and confocal laser scanning microscopy in combination with bacterial viability staining and polysaccharide staining were used to confirm the stimulatory effects of antibiotics on biofilms.Results
Most coagulase-negative staphylococcal clinical isolates were resistant to penicillin G (100%), gentamicin (83.3%) and oxacillin (91.7%) and susceptible to vancomycin (100%), ciprofloxacin (100%), and rifampicin (79.2%). Bacteria grown as adherent monolayers showed similar susceptibilities to their planktonic counterparts at mid-log phase. Isolates in a biofilm growth mode were more resistant to antibiotics than both planktonic cultures at mid-log phase and adherent monolayers; however they were equally resistant or less resistant than planktonic cells at stationary phase. Moreover, for some cell-wall active antibiotics, concentrations higher than conventional MICs were required to prevent the establishment of planktonic cultures from biofilms. Finally, the biofilm-growth of two S. capitis isolates could be enhanced by oxacillin at the highest achievable serum concentration.Conclusion
We conclude that the resistance of coagulase-negative staphylococci to multiple antibiotics initially remain similar when the bacteria shift from a planktonic growth mode into an early attached mode, then increase significantly as the adherent mode further develops. Furthermore, preformed biofilms of some CoNS are enhanced by oxacillin in a dose-dependent manner. 相似文献43.
44.
Daley MA Biewener AA 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2011,366(1570):1580-1591
Here, we used an obstacle treadmill experiment to investigate the neuromuscular control of locomotion in uneven terrain. We measured in vivo function of two distal muscles of the guinea fowl, lateral gastrocnemius (LG) and digital flexor-IV (DF), during level running, and two uneven terrains, with 5 and 7 cm obstacles. Uneven terrain required one step onto an obstacle every four to five strides. We compared both perturbed and unperturbed strides in uneven terrain to level terrain. When the bird stepped onto an obstacle, the leg became crouched, both muscles acted at longer lengths and produced greater work, and body height increased. Muscle activation increased on obstacle strides in the LG, but not the DF, suggesting a greater reflex contribution to LG. In unperturbed strides in uneven terrain, swing pre-activation of DF increased by 5 per cent compared with level terrain, suggesting feed-forward tuning of leg impedance. Across conditions, the neuromechanical factors in work output differed between the two muscles, probably due to differences in muscle-tendon architecture. LG work depended primarily on fascicle length, whereas DF work depended on both length and velocity during loading. These distal muscles appear to play a critical role in stability by rapidly sensing and responding to altered leg-ground interaction. 相似文献
45.
46.
William H. Clements Jeffrey L. Arnold Todd M. Koel Rob Daley Cathie Jean 《Aquatic Ecology》2011,45(1):137-149
We examined responses of benthic macroinvertebrate communities to natural geothermal discharges in 32 streams in Yellowstone
National Park (YNP), USA. Geothermal discharges played a major role in structuring benthic communities in YNP, as downstream
communities were characterized by low species richness, reduced abundance of EPT taxa and increased abundance of tolerant
caddisflies (Trichoptera), chironomids and non-insects. While some taxa were a subset of tolerant organisms that were also
common at references sites, others (the damselfly Argia sp., the caddisfly Oxyethira sp. and the exotic New Zealand mudsnail Potamopyrgus antipodarum Gray 1843) were found almost exclusively in geothermal streams. Because geothermal waters are a common feature of YNP, monitoring
programs designed to assess long-term status and trends of Yellowstone’s aquatic ecosystems must account for the influence
of these discharges. To separate geothermal effects from other potential anthropogenic disturbances in YNP (e.g., atmospheric
deposition, road construction, wastewater, global change), we developed a multimetric index based on responses of benthic
communities to geothermal discharges. Streams were placed into one of four geothermal categories based on conductivity (reference = < 150 μS/cm; low, moderate and high = 151–300, 301–600 and >600 μS/cm, respectively). The index clearly distinguished among
these categories and showed a well-defined threshold response to geothermal effects at very low levels of conductivity. Although
the index was specific to geothermal effects, the approach used to develop the index has broad applicability for other systems
where impacts of stressors must be assessed within the context of natural environmental gradients. Our findings may provide
important insights into how benthic macroinvertebrate communities respond to global change. Reduced discharge and warmer temperatures
predicted for Rocky Mountain streams may favor the establishment and expansion of exotic species such as New Zealand mudsnails
(P. antipodarum), which are highly tolerant of geothermal influences. 相似文献
47.
Maddalo G Chovanec P Stenberg-Bruzell F Nielsen HV Jensen-Seaman MI Ilag LL Kline KA Daley DO 《Proteomics》2011,11(19):3935-3941
Enterococcus faecalis is a gram-positive bacterium that is part of the indigenous microbiotica of humans and animals as well as an opportunistic pathogen. In this study, we have fractionated the membrane proteome of E. faecalis and identified many of its constituents by mass spectrometry. We present blue native-/SDS-PAGE reference maps that contain 102 proteins. These proteins are important for cellular homeostasis, virulence, and antibiotic intervention. Intriguingly, many proteins with no known function were also identified, indicating that there are substantial gaps in the knowledge of this organism's biology. On a more limited scale, we also provide insight into the composition of membrane protein complexes. This study is a first step toward elucidating the membrane proteome of E. faecalis, which is critical for a better understanding of how this bacterium interacts with a host and with the extracellular milieu. 相似文献
48.
Limited access to diagnostic services and the poor performance of current tests result in a failure to detect millions of tuberculosis cases each year. An accurate test that could be used at the point of care to allow faster initiation of treatment would decrease death rates and could reduce disease transmission. Previous attempts to develop such a test have failed, and success will require the marriage of biomarkers that are highly predictive for the disease with innovative technology that is reliable and affordable. Here, we review the status of research into point-of-care tests for active tuberculosis and discuss barriers to the development of such diagnostic tests. 相似文献
49.
Weisberg E Ray A Nelson E Adamia S Barrett R Sattler M Zhang C Daley JF Frank D Fox E Griffin JD 《PloS one》2011,6(9):e25351
Objectives
Clinical responses achieved with FLT3 kinase inhibitors in acute myeloid leukemia (AML) are typically transient and partial. Thus, there is a need for identification of molecular mechanisms of clinical resistance to these drugs. In response, we characterized MOLM13 AML cell lines made resistant to two structurally-independent FLT3 inhibitors.Methods
MOLM13 cells were made drug resistant via prolonged exposure to midostaurin and HG-7-85-01, respectively. Cell proliferation was determined by Trypan blue exclusion. Protein expression was assessed by immunoblotting, immunoprecipitation, and flow cytometry. Cycloheximide was used to determine protein half-life. RT-PCR was performed to determine FLT3 mRNA levels, and FISH analysis was performed to determine FLT3 gene expression.Results and Conclusions
We found that MOLM13 cells readily developed cross-resistance when exposed to either midostaurin or HG-7-85-01. Resistance in both lines was associated with dramatically elevated levels of cell surface FLT3 and elevated levels of phosphor-MAPK, but not phospho-STAT5. The increase in FLT3-ITD expression was at least in part due to reduced turnover of the receptor, with prolonged half-life. Importantly, the drug-resistant phenotype could be rapidly reversed upon withdrawal of either inhibitor. Consistent with this phenotype, no significant evidence of FLT3 gene amplification, kinase domain mutations, or elevated levels of mRNA was observed, suggesting that protein turnover may be part of an auto-regulatory pathway initiated by FLT3 kinase activity. Interestingly, FLT3 inhibitor resistance also correlated with resistance to cytosine arabinoside. Over-expression of FLT3 protein in response to kinase inhibitors may be part of a novel mechanism that could contribute to clinical resistance. 相似文献50.
Mutations of the Yku80 C terminus and Xrs2 FHA domain specifically block yeast nonhomologous end joining 总被引:5,自引:0,他引:5
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The nonhomologous end-joining (NHEJ) pathway of DNA double-strand break repair requires three protein complexes in Saccharomyces cerevisiae: MRX (Mre11-Rad50-Xrs2), Ku (Ku70-Ku80), and DNA ligase IV (Dnl4-Lif1-Nej1). Much is known about the interactions that mediate the formation of each complex, but little is known about how they act together during repair. A comprehensive yeast two-hybrid screen of the NHEJ factors of S. cerevisiae revealed all known interactions within the MRX, Ku, and DNA ligase IV complexes, as well as three additional, weaker interactions between Yku80-Dnl4, Xrs2-Lif1, and Mre11-Yku80. Individual and combined deletions of the Yku80 C terminus and the Xrs2 forkhead-associated (FHA) domain were designed based on the latter two-hybrid results. These deletions synergistically blocked NHEJ but not the telomere and recombination functions of Ku and MRX, confirming that these protein regions are functionally important specifically for NHEJ. Further mutational analysis of Yku80 identified a putative C-terminal amphipathic α-helix that is both required for its NHEJ function and strikingly similar to a DNA-dependent protein kinase interaction motif in human Ku80. These results identify a novel role in yeast NHEJ for the poorly characterized Ku80 C-terminal and Xrs2 FHA domains, and they suggest that redundant binding of DNA ligase IV facilitates completion of this DNA repair event. 相似文献