Assessment of specificity of eight chemical inhibitors using cDNA-expressed cytochromes P450

1. The selectivity of eight chemical inhibitors has been extensively evaluated with 10 cDNA-expressed human cytochrome P450 isoforms (CYP). The results indicate that sulphaphenazole, quinidine and α-naphthoflavone are selective inhibitors of CYP2C9 (IC₅₀ = 5 0.5-0.7 μM), CYP2D6 (0.3-0.4 μM) and CYP1A (0.05-5 μM) respectively on the basis of the IC₅₀, which are much lower than those of other P450 isoforms (> 10-fold). 2. Ketoconazole exhibited potent inhibition of both CYP3A4-catalysed metabolism of phenanthrene, testosterone, diazepam (IC₅₀ = 0.03-0.5 μM) and CYP1A1-catalysed deethylation of 7-ethoxycoumarin (0.33 μM). The selectivity of ketoconazole for other P450s was highly related to the concentration used. 3. Diethyldithiocarbamate, orphenadrine and furafylline were shown separately to be less selective inhibitors of CYP2E1, CYP2B6 and CYP1A isoforms by a broad range of IC₅₀ that overlap those observed with other P450 isoforms. 4. Furafylline, quinidine and α-naphthoflavone activated CYP3A4-catalysed phenanthrene metabolism by 1.7-, 2- and 15-fold respectively. 5. The selectivity of orphenadrine and ketoconazole was further examined by using inhibitory monoclonal antibodies (MAb). Inhibitory MAb specific for the individual P450 isoforms may be of greater value than chemical inhibitors.     

Whole-bone scaling of the avian pelvic limb

Birds form the largest extant group of bipedal animals and occupy a broad range of body masses, from grams to hundreds of kilograms. Additionally, birds occupy distinct niches of locomotor behaviour, from totally flightless strong runners such as the ratites (moa, kiwi, ostrich) to birds that may walk, dabble on water or fly. We apply a whole-bone approach to investigate allometric scaling trends in the pelvic limb bones (femur, tibiotarsus, tarsometatarsus) from extant and recently extinct birds of greatly different size, and compare scaling between birds in four locomotor groups; flightless, burst-flying, dabbling and flying. We also compare scaling of birds' femoral cross-sectional properties to data previously collected from cats. Scaling exponents were not significantly different between the different locomotor style groups, but elevations of the scaling relationships revealed that dabblers (ducks, geese, swans) have particularly short and slender femora compared with other birds of similar body mass. In common with cats, but less pronounced in birds, the proximal and distal extrema of the bones scaled more strongly than the diaphysis, and in larger birds the diaphysis occupied a smaller proportion of bone length than in smaller birds. Cats and birds have similar femoral cross-sectional area (CSA) for the same body mass, yet birds' bone material is located further from the bone's long axis, leading to higher second and polar moments of area and a greater inferred resistance to bending and twisting. The discrepancy in the relationship between outer diameter to CSA may underlie birds' reputation for having 'light' bones.     

Bony labyrinth shape variation in extant Carnivora: a case study of Musteloidea

The bony labyrinth provides a proxy for the morphology of the inner ear, a primary cognitive organ involved in hearing, body perception in space, and balance in vertebrates. Bony labyrinth shape variations often are attributed to phylogenetic and ecological factors. Here we use three‐dimensional (3D) geometric morphometrics to examine the phylogenetic and ecological patterns of variation in the bony labyrinth morphology of the most species‐rich and ecologically diversified traditionally recognized superfamily of Carnivora, the Musteloidea (e.g. weasels, otters, badgers, red panda, skunks, raccoons, coatis). We scanned the basicrania of specimens belonging to 31 species using high‐resolution X‐ray computed micro‐tomography (μCT) to virtually reconstruct 3D models of the bony labyrinths. Labyrinth morphology is captured by a set of six fixed landmarks on the vestibular and cochlear systems, and 120 sliding semilandmarks, slid at the center of the semicircular canals and the cochlea. We found that the morphology of this sensory structure is not significantly influenced by bony labyrinth size, in comparisons across all musteloids or in any of the individual traditionally recognized families (Mephitidae, Procyonidae, Mustelidae). PCA (principal components analysis) of shape data revealed that bony labyrinth morphology is clearly distinguishable between musteloid families, and permutation tests of the Kmult statistic confirmed that the bony labyrinth shows a phylogenetic signal in musteloids and in most mustelids. Both the vestibular and cochlear regions display morphological differences among the musteloids sampled, associated with the size and curvature of the semicircular canals, angles between canals, presence or absence of a secondary common crus, degree of lateral compression of the vestibule, orientation of the cochlea relative to the semicircular canals, proportions of the cochlea, and degree of curvature of its turns. We detected a significant ecological signal in the bony labyrinth shape of musteloids, differentiating semi‐aquatic taxa from non‐aquatic ones (the taxa assigned to terrestrial, arboreal, semi‐arboreal, and semi‐fossorial categories), and a significant signal for mustelids, differentiating the bony labyrinths of terrestrial, semi‐arboreal, arboreal, semi‐fossorial and semi‐aquatic species from each other. Otters and minks are distinguished from non‐aquatic musteloids by an oval rather than circular anterior canal, sinuous rather than straight lateral canal, and acute rather than straight angle between the posterior and lateral semicircular canals – each of these morphological characters has been related previously to animal sensitivity for detecting head motion in space.     

An allometric analysis of the number of muscle spindles in mammalian skeletal muscles

An allometric analysis of the number of muscle spindles in relation to muscle mass in mammalian (mouse, rat, guinea-pig, cat, human) skeletal muscles is presented. It is shown that the trend to increasing number as muscle mass increases follows an isometric (length) relationship between species, whereas within a species, at least for the only essentially complete sample (human), the number of spindles scales, on average, with the square root rather than the cube root of muscle mass. An attempt is made to reconcile these apparently discrepant relationships. Use of the widely accepted spindle density (number of spindles g(-1) of muscle) as a measure of relative abundance of spindles in different muscles is shown to be grossly misleading. It is replaced with the residuals of the linear regression of ln spindle number against ln muscle mass. Significant differences in relative spindle abundance as measured by residuals were found between regional groups of muscles: the greatest abundance is in axial muscles, including those concerned with head position, whereas the least is in muscles of the shoulder girdle. No differences were found between large and small muscles operating in parallel, or between antigravity and non-antigravity muscles. For proximal vs. distal muscles, spindles were significantly less abundant in the hand than the arm, but there was no difference between the foot and the leg.     

不同生长年限滇重楼的生物量分配与异速生长研究

目的 比较不同产地和生长年限栽培滇重楼Paris polyphylla var. yunnanensis生物量和性状差异,并对植株生物量积累和生长发育规律进行异速生长分析。方法 使用Pearson相关分析研究滇重楼根茎生物量与采集地经纬度、气候因子间的相关性;单因素方差分析（One-Way ANOVA）与独立样本T检验用于样品间植物性状的差异显著性比较;利用标准化主轴回归分析（standardized major axisregression）对滇重楼的生物量积累和生长发育规律进行异速生长研究。结果 研究表明12个不同产地的5年生滇重楼根茎生物量平均值在1.19～19.73 g,不同产地之间具有显著差异（P<0.05）,但该差异与产地经纬度、年均温度、年均降水量之间不存在显著相关性（P>0.05）。滇重楼植株的根茎生物量均随生长年限增加而增加,种植5年后根茎生物量一直呈现快速积累趋势。相同生长年限植株中,云南省元阳县样品根茎生物量显著高于姚安县样品（P<0.05）,并且数值具有更高的变化范围。滇重楼植株的总生物量、株高、叶生物量、叶长、叶宽、叶面积均随生长年限增加而增...     

太行山猕猴下颌骨的异速生长分析

目的：探讨太行山猕猴下颌骨随年龄变化的形态学改变,为太行山猕猴的体质学、医学实验、进一步确定其分类地位提供可靠的依据。方法：30例太行山猕猴下颌骨标本,按其齿序及牙齿磨损程度的不同分成6组,并对其18项变量进行了测量、统计和分析。结果：下颌骨的有关变量与齿序和牙齿磨损程度成异速生长,即有关变量在生长、发育过程中的变化与其年龄相关,并且不同变量在不同年龄段呈现不同的生长模式。结论：下颌体各变量的变化趋势与其功能是相适应的,与猕猴的食物组成和其取食习性亦具有相关关系。     

Enlarged limbic structures in the human brain: the anterior thalamus and medial mamillary body

Major paradigms about human evolution stress the increase of cognitive capabilities, while considering our emotional and limbic systems to be relatively unchanged. Morphometric analyses of two limbic structures, the anterior thalamic nuclei8 (AP) and the medial mamillary bodies (MB), in 27 primate species show, however, that: (1) human nuclei are as large as MB or larger AP than differences in anthropoid brain sizes predict; and (2) prosimians and anthropoid patterns differ.     

The Homo floresiensis cranium (LB1): size, scaling, and early Homo affinities

The skeletal remains of a diminutive small-brained hominin found in Late Pleistocene cave deposits on the island of Flores, Indonesia were assigned to a new species, Homo floresiensis [Brown P, et al. (2004) A new small-bodied hominin from the Late Pleistocene of Flores, Indonesia. Nature 431: 1055-1061]. A dramatically different interpretation is that this material belongs not to a novel hominin taxon but to a population of small-bodied modern humans affected, or unaffected, by microcephaly. The debate has primarily focused on the size and shape of the endocranial cavity of the type specimen, LB1, with less attention being paid to the morphological evidence provided by the rest of the LB1 cranium and postcranium, and no study thus far has addressed the problem of how scaling would affect shape comparisons between a diminutive cranium like LB1 and the much larger crania of modern humans. We show that whether or not the effects of its small cranial size are accounted for, the external cranial morphology of the LB1 cranium cannot be accommodated within a large global sample of normal modern human crania. Instead, the shape of LB1, which is shown by multivariate analysis to differ significantly from that of modern humans, is similar to that of Homo erectus sensu lato, and, to a lesser extent, Homo habilis. Our results are consistent with hypotheses that suggest the Liang Bua specimens represent a diminutive population closely related to either early H. erectus s. l. from East Africa and/or Dmanisi or to H. habilis.