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91.
Meirovitch H 《Current opinion in structural biology》2007,17(2):181-186
The Helmholtz free energy, F, plays an important role in proteins because of their rugged potential energy surface, which is 'decorated' with a tremendous number of local wells (denoted microstates, m). F governs protein folding, whereas differences DeltaF(mn) determine the relative populations of microstates that are visited by a flexible cyclic peptide or a flexible protein segment (e.g. a surface loop). Recently developed methodologies for calculating DeltaF(mn) (and entropy differences, DeltaS(mn)) mainly use thermodynamic integration and calculation of the absolute F; interesting new approaches in these categories are the adaptive integration method and the hypothetical scanning molecular dynamics method, respectively. 相似文献
92.
New statistical modelling methods, such as neural networks (NNs), allow us to take a step further in the understanding of
complex relations in aquatic ecosystems. In this paper the results from the analysis of macro-invertebrate communities in
a complex riverine environment are presented. We attempted to explain observed changes in species composition and abundance
with neural network modelling methods and compared the results to linear regression. The NN method used is an improved form
of the RF5 algorithm, developed to effectively discover numeric laws from data. RF5 uses Product Unit Networks (PUNs), which
are in effect multivariate non-discrete power functions. The data set consisted of a 10-year time series of monthly samples
of macro-invertebrates on artificial substrates in the rivers Rhine and Meuse in the Netherlands. During this period the invertebrate
community has largely changed coinciding with the␣invasion of Ponto-Caspian crustaceans. We used physical–chemical data and
data on the abundance of the invasive taxa Corophium curvispinum and Dikerogammarus villosis to explain the observed changes in the resident invertebrate community. The analyses showed temperature, abundance of invasive
taxa and peak discharges as important factors. Comparison of the results from NN modelling to linear regression revealed that
the factors temperature and abundance of Dikerogammarus
villosis explained equally well in both cases. Only the neural network was able to use information on peak discharge and timing of
the peak in the previous winter to improve model performances. Neural networks are known to yield excellent modelling results,
a drawback however is their lack of transparency or their ‘black box’ character. The use of relatively easy interpretable
(white box) PUNs allows us to investigate the extracted relations in more detail and can enhance our understanding of ecosystem
functioning. Our results show that peak discharges might be an important factor structuring invertebrate communities in rivers
and hint on the existence of interacting effects from invasive species and discharge peaks. They finally show the value of
biological data sets that are collected over a long period and in a highly standardised way. 相似文献
93.
Forest P. Hayes Joshua J. Millspaugh Eric J. Bergman Ragan M. Callaway Chad J. Bishop 《The Journal of wildlife management》2022,86(2):e22175
Across much of North America, populations of moose (Alces alces) are declining because of disease, predation, climate change, and anthropogenic-driven habitat loss. Contrary to this trend, populations of moose in Colorado, USA, have continued to grow. Studying successful (i.e., persistent or growing) populations of moose can facilitate continued conservation by identifying habitat features critical to persistence of moose. We hypothesized that moose using habitat with higher quality willow (Salix spp.) would have a higher probability of having a calf-at-heel (i.e., calving success). We evaluated moose calving success using repeated ground observations of collared individuals with calves in an occupancy model framework to account for detection probability. We then evaluated the impact of willow habitat quality and nutrition on moose calving success by studying 2 spatially segregated populations of moose in Colorado. Last, we evaluated correlations between willow characteristics (browse intensity, height, cover, leaf length, and species) and willow nutrition (dry matter digestibility [DMD]) to assess the utility of using those characteristics to assess willow nutrition. We found willow height and cover had a high probability of being positively associated with higher individual-level calving success. Willow DMD, browse intensity, and leaf length were not predictive of individual moose calving success; however, the site with higher mean DMD consistently had higher mean estimates of calving success for the same year. Our results suggest surveying DMD is likely not a useful metric for assessing differences in calving success of individual moose but may be of use at population levels. Further, the assessment of willow morphology and density may be used to identify areas that support higher levels of moose calving success. 相似文献
94.
95.
Hagai Tavori Yan Ru Su Patricia G. Yancey Ilaria Giunzioni Ashley J. Wilhelm John L. Blakemore Manal Zabalawi MacRae F. Linton Mary G. Sorci-Thomas Sergio Fazio 《Journal of lipid research》2015,56(3):635-643
Tissue cholesterol accumulation, macrophage infiltration, and inflammation are features of atherosclerosis and some forms of dermatitis. HDL and its main protein, apoAI, are acceptors of excess cholesterol from macrophages; this process inhibits tissue inflammation. Recent epidemiologic and clinical trial evidence questions the role of HDL and its manipulation in cardiovascular disease. We investigated the effect of ectopic macrophage apoAI expression on atherosclerosis and dermatitis induced by the combination of hypercholesterolemia and absence of HDL in mice. Hematopoietic progenitor cells were transduced to express human apoAI and transplanted into lethally irradiated LDL receptor−/−/apoAI−/− mice, which were then placed on a high-fat diet for 16 weeks. Macrophage apoAI expression reduced aortic CD4+ T-cell levels (−39.8%), lesion size (−25%), and necrotic core area (−31.6%), without affecting serum HDL or aortic macrophage levels. Macrophage apoAI reduced skin cholesterol by 39.8%, restored skin morphology, and reduced skin CD4+ T-cell levels. Macrophage apoAI also reduced CD4+ T-cell levels (−32.9%) in skin-draining lymph nodes but had no effect on other T cells, B cells, dendritic cells, or macrophages compared with control transplanted mice. Thus, macrophage apoAI expression protects against atherosclerosis and dermatitis by reducing cholesterol accumulation and regulating CD4+ T-cell levels, without affecting serum HDL or tissue macrophage levels. 相似文献
96.
97.
98.
Background
Insertion sequences (ISs) are approximately 1 kbp long “jumping” genes found in prokaryotes. ISs encode the protein Transposase, which facilitates the excision and reinsertion of ISs in genomes, making these sequences a type of class I (“cut-and-paste”) Mobile Genetic Elements. ISs are proposed to be involved in the reductive evolution of symbiotic prokaryotes. Our previous sequencing of the genome of the cyanobacterium ‘Nostoc azollae’ 0708, living in a tight perpetual symbiotic association with a plant (the water fern Azolla), revealed the presence of an eroding genome, with a high number of insertion sequences (ISs) together with an unprecedented large proportion of pseudogenes. To investigate the role of ISs in the reductive evolution of ‘Nostoc azollae’ 0708, and potentially in the formation of pseudogenes, a bioinformatic investigation of the IS identities and positions in 47 cyanobacterial genomes was conducted. To widen the scope, the IS contents were analysed qualitatively and quantitatively in 20 other genomes representing both free-living and symbiotic bacteria.Results
Insertion Sequences were not randomly distributed in the bacterial genomes and were found to transpose short distances from their original location (“local hopping”) and pseudogenes were enriched in the vicinity of IS elements. In general, symbiotic organisms showed higher densities of IS elements and pseudogenes than non-symbiotic bacteria. A total of 1108 distinct repeated sequences over 500 bp were identified in the 67 genomes investigated. In the genome of ‘Nostoc azollae’ 0708, IS elements were apparent at 970 locations (14.3%), with 428 being full-length. Morphologically complex cyanobacteria with large genomes showed higher frequencies of IS elements, irrespective of life style.Conclusions
The apparent co-location of IS elements and pseudogenes found in prokaryotic genomes implies earlier IS transpositions into genes. As transpositions tend to be local rather than genome wide this likely explains the proximity between IS elements and pseudogenes. These findings suggest that ISs facilitate the reductive evolution in for instance in the symbiotic cyanobacterium ‘Nostoc azollae’ 0708 and in other obligate prokaryotic symbionts.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1386-7) contains supplementary material, which is available to authorized users. 相似文献99.
Chronic mTOR inhibition in mice with rapamycin alters T,B, myeloid,and innate lymphoid cells and gut flora and prolongs life of immune‐deficient mice
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Vincent Hurez Vinh Dao Aijie Liu Srilakshmi Pandeswara Jonathan Gelfond Lishi Sun Molly Bergman Carlos J. Orihuela Veronica Galvan Álvaro Padrón Justin Drerup Yang Liu Paul Hasty Zelton Dave Sharp Tyler J. Curiel 《Aging cell》2015,14(6):945-956
The mammalian (mechanistic) target of rapamycin (mTOR) regulates critical immune processes that remain incompletely defined. Interest in mTOR inhibitor drugs is heightened by recent demonstrations that the mTOR inhibitor rapamycin extends lifespan and healthspan in mice. Rapamycin or related analogues (rapalogues) also mitigate age‐related debilities including increasing antigen‐specific immunity, improving vaccine responses in elderly humans, and treating cancers and autoimmunity, suggesting important new clinical applications. Nonetheless, immune toxicity concerns for long‐term mTOR inhibition, particularly immunosuppression, persist. Although mTOR is pivotal to fundamental, important immune pathways, little is reported on immune effects of mTOR inhibition in lifespan or healthspan extension, or with chronic mTOR inhibitor use. We comprehensively analyzed immune effects of rapamycin as used in lifespan extension studies. Gene expression profiling found many and novel changes in genes affecting differentiation, function, homeostasis, exhaustion, cell death, and inflammation in distinct T‐ and B‐lymphocyte and myeloid cell subpopulations. Immune functions relevant to aging and inflammation, and to cancer and infections, and innate lymphoid cell effects were validated in vitro and in vivo. Rapamycin markedly prolonged lifespan and healthspan in cancer‐ and infection‐prone mice supporting disease mitigation as a mechanism for mTOR suppression‐mediated longevity extension. It modestly altered gut metagenomes, and some metagenomic effects were linked to immune outcomes. Our data show novel mTOR inhibitor immune effects meriting further studies in relation to longevity and healthspan extension. 相似文献
100.
Tavori H Aviram M Khatib S Musa R Mannheim D Karmeli R Vaya J 《Free radical biology & medicine》2011,50(1):148-156
Paraoxonase 1 (PON1) is an HDL-associated lactonase with antiatherogenic properties. These include dampening the oxidation properties of human carotid lesion lipid extract (LLE), which in turn inactivates the enzyme. The aims of this study were to identify the PON1 inhibitor in LLE and explore the mechanism of inhibition. LLE inhibited both recombinant PON1 and HDL-PON1 lactonase activity in a dose- and time-dependent manner. Addition of antioxidants or electrophiles to LLE did not prevent PON1 inhibition. LLE was unable to inhibit a PON1 mutant lacking Cys284, whereas it did inhibit all other PON1 mutants tested. The inhibitor in the LLE was identified as linoleic acid hydroperoxide (LA-OOH) and inhibition was specific to this hydroperoxide. During its inhibition, PON1 acted like a peroxidase enzyme, reducing LA-OOH to LA-hydroxide via its Cys284. A similar reaction occurred with external thiols, such as DDT or cysteine, which also prevented PON1 inhibition and restored enzyme activity after inhibition. Thus, the antiatherogenic properties of HDL could be, at least in part, related to the sulfhydryl-reducing characteristics of its associated PON1, which are further protected and recycled by the sulfhydryl amino acid cysteine. 相似文献