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The solution flexibility of carbohydrates influences a variety of molecular recognition and regulatory processes. For aldoses and other monosaccharides, this flexibility is dictated by the orientations of the various hydroxyl (OH) groups present, which influences conformer and anomer ratios, interactions among these OH groups, and interactions between them and the surrounding solvent. Depending on the number and position of axial OH groups, a variety of structures can coexist in solutions at equilibrium. In 1950, as part of his pioneering studies on the shape of pyranoside rings, Reeves described the Δ2 effect, the greater destabilization of the pyranose ring conformation when the OH group on carbon 2 (C2) is in the axial position. It was later proposed by Angyal that the Δ2 effect could be cancelled by the presence of an axial OH on C3, termed here the “C3 effect.” Employing size‐exclusion chromatography, an entropically‐controlled separation technique, we have investigated whether or not the C3 and Δ2 effects indeed do compensate for one another with respect to their influence on the solution flexibility of select aldohexoses and aldopentoses. As will be seen, while qualitatively and semiquantitatively this mutual cancellation of effects does occur in aldohexoses, it does not appear to do so in aldopentoses. An explanation for the latter appears to lie in the variety of anomers and conformers present in equilibrium solutions of those aldopentoses studied and in the relative entropic contribution of individual conformers or anomers to the total solution flexibility. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 703–711, 2014.  相似文献   

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Gemins 2-8 and Unr-interacting protein (UNRIP) are intimate partners of the survival motor neuron (SMN) protein, which is the determining factor for the neuromuscular disorder spinal muscular atrophy (SMA). The most documented role of SMN, Gemins and UNRIP occurs within the large macromolecular SMN complex and involves the cytoplasmic assembly of spliceosomal uridine-rich small nuclear ribonucleoproteins (UsnRNPs), a housekeeping process critical in all cells. Several reports detailing alternative functions for SMN in either motor neurons or skeletal muscles may, however, hold the answer to the extreme neuromuscular tissue specificity observed in SMA. Recent discoveries indicate that collaboration between SMN and Gemins also extends to these non-canonical functions, hence raising the possibility that mutations in Gemin genes may be the cause of unlinked neuromuscular hereditary syndromes. This review evaluates the functions of Gemins and UNRIP inside the SMN complex and discusses whether these less notorious SMN complex members are capable of acting independently of SMN.  相似文献   

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The elongation of π‐conjugated bridges between the donor (D) and the acceptor (A) represents a feasible strategy towards enhancement of light‐harvesting in both breadth and depth of organic D‐π‐A dyes suitable for nanocrystalline TiO2‐based dye‐sensitized solar cells (DSSCs). Here, a series of organic dyes with elongating conjugated bridges is synthesized and characterized. DSSC devices employing a cobalt (II/III) redox electrolyte are fabricated using these dyes as light‐harvesting sensitizers. Compared to a dye with the 3,4‐ethylenedioxythiophene (EDOT) linker ( G188 ), the three counterparts with further extended π‐bridges present gradually red‐shifted electronic absorption spectra and a persistent decrease in oxidation potential. The photocurrent action spectra show that the extension of π‐conjugated bridges decreases the open‐circuit photovoltage. The best performance is shown in G268 with a short‐circuit photocurrent density (Jsc) of 16.27 mA cm2, an open‐circuit photovoltage (Voc) of 0.83 V, and a fill factor (FF) of 0.67, corresponding to an overall conversion efficiency of 9.24%. Unexpectedly, G270, which has with the longest π‐bridge , showed the lowest Jsc, Voc, and efficiency.  相似文献   

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To maintain normal cellular and physiological function, sufficient oxygen is required. Recently, evidence has suggested that hypoxia, either pathological or environmental, may influence bone health. It appears that bone cells are distinctly responsive to hypoxic stimuli; for better or worse, this is still yet to be elucidated. Hypoxia has been shown to offer potentially therapeutic effects for bone by inducing an osteogenic–angiogenic response, although, others have noted excessive osteoclastic bone resorption instead. Much evidence suggests that the hypoxic‐inducible pathway is integral in mediating the changes in bone metabolism. Furthermore, many factors associated with hypoxia including changes in energy metabolism, acid–base balance and the increased generation of reactive oxygen species, are known to influence bone metabolism. This review aims to examine some of the putative mechanisms responsible for hypoxic‐induced alterations of bone metabolism, with regard to osteoclasts and osteoblasts, both positive and negative.  相似文献   

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Objective: To investigate the effect of maternal dietary ω‐3 polyunsaturated fatty acid (PUFA) deficiency and repletion on food appetite signaling. Research Methods and Procedures: Sprague‐Dawley rat dams were maintained on diets either supplemented with (CON) or deficient in (DEF) ω‐3 PUFA. All offspring were raised on the maternal diet until weaning. After weaning, two groups remained on the respective maternal diet (CON and DEF groups), whereas a third group, born of dams fed the DEF diet, were switched to the CON diet (REC). Experiments on food intake began when the male rats reached 16 weeks of age. Food intake was stimulated either by a period of food restriction, by blocking glucose utilization (by 2‐deoxyglucose injection), or by blocking β‐oxidation of fatty acids (by β‐mercaptoacetate injection). Results: DEF animals consumed more than CON animals in response to all stimuli, with the greatest difference (1.9‐fold) demonstrated following administration of 2‐deoxyglucose. REC animals also consumed more than CON animals in response to food restriction and 2‐deoxyglucose but not to β‐mercaptoacetate. Discussion: These findings indicate that supply of ω‐3 PUFA, particularly during the perinatal period, plays a role in the normal development of mechanisms controlling food intake, especially glucoprivic (i.e. reduced glucose availability) appetite signaling. Dietary repletion of ω‐3 PUFA from 3 weeks of age restored intake responses to fatty acid metabolite signaling but did not reverse those in response to food restriction or glucoprivic stimuli.  相似文献   

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A recent study in Molecular Cell uncovered parallel yet distinct SUMOylation pathways that provide insights into molecular mechanisms of transrepression mediated by activated nuclear receptors LXRalpha/beta and PPARgamma, thereby clarifying receptor, signal, and gene specificity of transrepression in inflammatory processes.  相似文献   

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The aging process involves changes in immune regulation, i.e. adaptive immunity declines whereas innate immunity becomes activated. NF-kappaB signaling is the master regulator of the both immune systems. Two recent articles highlight the role of the NF-kappaB system in aging and immune responses. Adler et al showed that the NF-kappaB binding domain is the genetic regulatory motif which is most strongly associated with the aging process. Kwon et al studying HIV-1 infection and subsequent immune deficiency process demonstrated that HIV-1 Tat protein binds to SIRT1 protein, a well-known longevity factor, and inhibits the SIRT1-mediated deacetylation of the p65 component of the NF-kappaB complex. As a consequence, the transactivation efficiency of the NF-kappaB factor was greatly potentiated, leading to the activation of immune system and later to the decline of adaptive immunity. These observations support the scenario where immune responses and aging process can be enforced by the potentiation of NF-kappaB transactivation efficiency. Longevity factors, such as SIRT1 and its activators, might regulate the efficiency of the NF-kappaB signaling, the major outcome of which is inflamm-aging via proinflammatory responses.  相似文献   

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Babin V  Roland C  Sagui C 《Proteins》2011,79(3):937-946
The α-sheet has been speculated to play a role as a toxic conformer in amyloid diseases. However, except for relatively short fragments, its detection has remained elusive. Here, we present molecular dynamics simulations that support the existence of the α-sheet as a stable, metastable, or long-lived secondary structure in polyglutamine and, to a lesser extent, in polyasparagine aggregates.  相似文献   

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Isotopic analysis of rock samples showed anomalously 18O-depleted reconstructed isotopic composition of paleo-meteoric water over southern Israel between the Late Cretaceous and the Early Miocene, with δ18OW as low as −14‰ [SMOW]. This range is significantly “lighter” than the expected values for rain at the relevant paleo-latitudes (~ 8°N to 25°N). It is similar or lighter than areas with meteoric water at the present climate, in which rainfall contribution from tropical cyclone (TC) is significant. Rainfall from TCs is 18O-depleted because of the recirculation of the vapor into repeated precipitation or distillation cycles. A paleo-geographic reconstruction of the region shows that throughout the period there was a warm ocean to the east and southeast of the relevant area. Thus, TCs formed over the ocean and made landfall on the coastline at a distance of 300 to 400 km to the east. The reconstructed composition of the rainwater implies dominance of TCs at these times. Furthermore, the combination of warmer seas and lighter rainwater than at present suggests that the TCs were more dominant than in the most TC-prone coastal areas at the present climate. The results of the present study suggest that climate during the relevant time periods was very different from the present, with TC activity similar or exceeding the most TC prone locations in the world at the present climate. This might also hint that warmer sea waters in the geological past were conducive to greater TC activity than in the present climate. Answering this question requires additional research.  相似文献   

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A gene for speed? The evolution and function of α‐actinin‐3   总被引:1,自引:0,他引:1  
The alpha-actinins are an ancient family of actin-binding proteins that play structural and regulatory roles in cytoskeletal organisation and muscle contraction. alpha-actinin-3 is the most-highly specialised of the four mammalian alpha-actinins, with its expression restricted largely to fast glycolytic fibres in skeletal muscle. Intriguingly, a significant proportion ( approximately 18%) of the human population is totally deficient in alpha-actinin-3 due to homozygosity for a premature stop codon polymorphism (R577X) in the ACTN3 gene. Recent work in our laboratory has revealed a strong association between R577X genotype and performance in a variety of athletic endeavours. We are currently exploring the function and evolutionary history of the ACTN3 gene and other alpha-actinin family members. The alpha-actinin family provides a fascinating case study in molecular evolution, illustrating phenomena such as functional redundancy in duplicate genes, the evolution of protein function, and the action of natural selection during recent human evolution.  相似文献   

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In recent years, studies of bird-habitat relationships undertaken in the context of habitat fragmentation have led to the widespread use of species categorisation according to their response to edge alongside mature forest patches (edge species, interior species, interior-edge generalist species). In other research contexts, especially in less fragmented landscapes dominated by a forested land base in various age classes, bird-habitat relationships are often described in relation to their use of various successional stages (early-successional species, mature forest species, generalist species). A simple comparison of these two commonly-used classifications schemes in a close geographical range for 60 species in eastern North America as well as for 36 species in north-western Europe clearly reveals that in these two particular biomes the two classifications are not independent. We believe that this association is not only a semantic issue and has important ecological consequences. For example, almost all edge species are associated with early-successional habitats when a wide range of forest age-classes are found in a given area. Accordingly, we suggest that most species considered to prefer edge habitats in agricultural landscapes are in fact only early-successional species that could not find shrubland conditions apart from the exposed edges of mature forest fragments. To be considered a true edge species, a given species should require the simultaneous availability of more than one habitat type and consequently should be classified as a habitat generalist in its use of successional stages. However, 28 out of 30 recognised edge species were considered habitat specialists in terms of successional status. Based on these results, we conclude that "real edge species" are probably quite rare and that we should make a difference between true edge species and species which in some landscapes, happen to find their habitat requirements on edges.  相似文献   

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