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221.
The International Journal of Life Cycle Assessment - A circular (bio)economy is sustained through use of secondary raw material and biomass feedstock. In life cycle assessment (LCA), the approach...  相似文献   
222.
Hearing relies on faithful signal transmission by cochlear inner hair cells (IHCs) onto auditory fibres over a wide frequency and intensity range. Exocytosis at IHC ribbon synapses is triggered by Ca2+ inflow through CaV1.3 (L-type) Ca2+ channels. We investigated the macroscopic (whole-cell) and elementary (cell-attached) properties of Ca2+ currents in IHCs positioned at the middle turn (frequency ∼2 kHz) of the adult gerbil cochlea, which is their most sensitive hearing region. Using near physiological recordings conditions (body temperature and a Na+ based extracellular solution), we found that the macroscopic Ca2+ current activates and deactivates very rapidly (time constant below 1 ms) and inactivates slowly and only partially. Single-channel recordings showed an elementary conductance of 15 pS, a sub-ms latency to first opening, and a very low steady-state open probability (P o: 0.024 in response to 500-ms depolarizing steps at ∼−18 mV). The value of P o was significantly larger (0.06) in the first 40 ms of membrane depolarization, which corresponds to the time when most Ca2+ channel openings occurred clustered in bursts (mean burst duration: 19 ms). Both the P o and the mean burst duration were smaller than those previously reported in high-frequency basal IHCs. Finally, we found that middle turn IHCs are likely to express about 4 times more Ca2+ channels per ribbon than basal cells. We propose that middle-turn IHCs finely-tune CaV1.3 Ca2+ channel gating in order to provide reliable information upon timing and intensity of lower-frequency sounds.  相似文献   
223.
Cofactor-independent phosphoglycerate mutase (iPGAM) is essential for the growth of C. elegans but is absent from humans, suggesting its potential as a drug target in parasitic nematodes such as Brugia malayi, a cause of lymphatic filariasis (LF). iPGAM''s active site is small and hydrophilic, implying that it may not be druggable, but another binding site might permit allosteric inhibition. As a comprehensive assessment of iPGAM''s druggability, high-throughput screening (HTS) was conducted at two different locations: ∼220,000 compounds were tested against the C. elegans iPGAM by Genzyme Corporation, and ∼160,000 compounds were screened against the B. malayi iPGAM at the National Center for Drug Screening in Shanghai. iPGAM''s catalytic activity was coupled to downstream glycolytic enzymes, resulting in NADH consumption, as monitored by a decline in visible-light absorbance at 340 nm. This assay performed well in both screens (Z′-factor >0.50) and identified two novel inhibitors that may be useful as chemical probes. However, these compounds have very modest potency against the B. malayi iPGAM (IC50 >10 µM) and represent isolated singleton hits rather than members of a common scaffold. Thus, despite the other appealing properties of the nematode iPGAMs, their low druggability makes them challenging to pursue as drug targets. This study illustrates a “druggability paradox” of target-based drug discovery: proteins are generally unsuitable for resource-intensive HTS unless they are considered druggable, yet druggability is often difficult to predict in the absence of HTS data.  相似文献   
224.
Our species exhibits spectacular success due to cumulative culture. While cognitive evolution of social learning mechanisms may be partially responsible for adaptive human culture, features of early human social structure may also play a role by increasing the number potential models from which to learn innovations. We present interview data on interactions between same-sex adult dyads of Ache and Hadza hunter-gatherers living in multiple distinct residential bands (20 Ache bands; 42 Hadza bands; 1201 dyads) throughout a tribal home range. Results show high probabilities (5%–29% per year) of cultural and cooperative interactions between randomly chosen adults. Multiple regression suggests that ritual relationships increase interaction rates more than kinship, and that affinal kin interact more often than dyads with no relationship. These may be important features of human sociality. Finally, yearly interaction rates along with survival data allow us to estimate expected lifetime partners for a variety of social activities, and compare those to chimpanzees. Hadza and Ache men are estimated to observe over 300 men making tools in a lifetime, whereas male chimpanzees interact with only about 20 other males in a lifetime. High intergroup interaction rates in ancestral humans may have promoted the evolution of cumulative culture.  相似文献   
225.
In this paper we describe a hitherto undocumented modification of the dental enamel surface observed in an Early Bronze Age population from northern Italy. The defect, which can be described as a curvilinear groove, is located on the lingual surface of incisors and canines in the upper jaw. This groove, documented both in the permanent and deciduous dentition, is located at approximately 1 mm from the cervix and extends from the mesiolingual to the distolingual surface. The occurrence of the groove is not related to the sex of the affected individuals, but its degree of expression is related to age at death. Because of its morphology, the groove cannot be considered as a result of disruptions in the process of enamel deposition. At the present stage of research we suggest that the groove might have been the result of some kind of dental erosion caused by as yet unidentified chemical factors. Am J Phys Anthropol 154:609–614, 2014. © 2014 Wiley Periodicals, Inc.  相似文献   
226.
The performances of MM2 andab-initio SCF STO-3G calculations to describe conformational changes in (CH2OCHO)2 in vacuo and in solution are examined. We present and justify a simple procedure to add solvent effects to the MM2 conformational energies. The analysis is focused on the detection of non-additive effects in simultaneous conformational changes. We have found that the -CH2-CH2-group is generally effective in decoupling simultaneous conformational changes. The non-additive effects, actually present in specific classes of conformational changes, are reduced by a solvent contribution when full SCF calculations are employed, and emphasized when MM2 + solvent calculations are employed. A rationale of this finding is presented, and some suggestions are made for the correction of this artifact, due to the use of rigid charges.  相似文献   
227.
228.
Soil biomes are vast, exceptionally diverse and crucial to the health of ecosystems and societies. Soils also contain an appreciable, but understudied, diversity of opportunistic human pathogens. With climate change and other forms of environmental degradation potentially increasing exposure risks to soilborne pathogens, it is necessary to gain a better understanding of their ecological drivers. Here we use the Galleria mellonella insect virulence model to selectively isolate pathogenic bacteria from soils in Cornwall (UK). We find a high prevalence of pathogenic soil bacteria with two genera, Providencia and Serratia, being especially common. Providencia alcalifaciens, P. rustigianii, Serratia liquefaciens and S. plymuthica strains were studied in more detail using phenotypic virulence and antibiotic resistance assays and whole-genome sequencing. Both genera displayed low levels of antibiotic resistance and antibiotic resistance gene carriage. However, Serratia isolates were found to carry the recently characterized metallo-β-lactamase blaSPR-1 that, although not conferring high levels of resistance in these strains, poses a potential risk of horizontal transfer to other pathogens where it could be fully functional. The Galleria assay can be a useful approach to uncover the distribution and identity of pathogenic bacteria in the environment, as well as uncover resistance genes with an environmental origin.  相似文献   
229.
Analysis of ungulate bones recovered from a number of Upper and Middle Palaeolithic sites in southern Italy revealed differences in the presence of anatomical elements. There is a lack of clear evidence of carnivore activities, and differences can be attributed to human activity. Indeed, these differences were probably due to different patterns of skeletal exploitation between Homo neanderthalensis and H. sapiens. Small limb bones (carpals, tarsals, sesamoids, long bone epiphyses and especially phalanges) are rarely found in Middle Palaeolithic deposits, but are abundant in the Upper Palaeolithic. The observation of unidentified bone fragments at these sites indicates that during the middle Palaeolithic, marrow extraction regarded essentially the treatment of long bones. First and second phalanges were not frequently used for this practice, but they were often fragmented by H. sapiens. Lack of these bones among the remains of meals of Neanderthal suggests that these bones were probably destroyed by their utilisation as fuel.  相似文献   
230.
Recently, a number of articles have been published on the mechanisms of dental development, and in particular on the genetic control of dental formation. As a specific example of the potential of this kind of research for paleoanthropological studies, cusp areas of upper molars of two species of South African Australopithecines (Australopithecus africanus, A. robustus) have been examined. The results suggest notable differences between the two species, possibly related to markedly different developmental pathways that are still far from clear in their details.  相似文献   
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