Os intermetatarseum: A heritable accessory bone of the human foot

The os intermetatarseum is a relatively common accessory bone of the human foot located at the tarsometatarsal border between the first and second metatarsals. It can occur as an independent ossicle or as an osseous spur projecting from the proximal ends of the first two metatarsals, or the distal end of the first cuneiform. To determine the frequency of this congenital defect in native North American groups and East Asians from Japan, the skeletons of 846 Native Americans and 125 modern Japanese and Ainu were examined for the presence of the os intermetatarseum. The North American skeletons are from archaeological sites in various parts of Canada and the United States, including the Arctic coast, the Subarctic, the Aleutian Islands, the Northern Plains, the Illinois River area, and the Southwest. Overall frequencies ranged from no occurrence among the Arctic samples to 8% of individuals from Pecos Pueblo. Second metatarsal spurs occurred in particularly high frequencies among American Indians, whereas the East Asians were only found to have os intermetatarseums associated with the first cuneiform. Because pedigrees have shown the os intermetatarseum to be an inherited defect, its high frequency among some Native Americans may be due, in part, to a higher degree of genetic relatedness among the individuals in the North American samples than among the relatively modern East Asians. Am J Phys Anthropol 107:199–209, 1998. © 1998 Wiley-Liss, Inc.     

Ecological divergence and medial cuneiform morphology in gorillas

Gorillas are more closely related to each other than to any other extant primate and are all terrestrial knuckle-walkers, but taxa differ along a gradient of dietary strategies and the frequency of arboreality in their behavioral repertoire. In this study, we test the hypothesis that medial cuneiform morphology falls on a morphocline in gorillas that tracks function related to hallucial abduction ability and relative frequency of arboreality. This morphocline predicts that western gorillas, being the most arboreal, should display a medial cuneiform anatomy that reflects the greatest hallucial abduction ability, followed by grauer gorillas, and then by mountain gorillas. Using a three-dimensional methodology to measure angles between articular surfaces, relative articular and nonarticular areas, and the curvatures of the hallucial articular surface, the functional predictions are partially confirmed in separating western gorillas from both eastern gorillas. Western gorillas are characterized by a more medially oriented, proportionately larger, and more mediolaterally curved hallucial facet than are eastern gorillas. These characteristics follow the predictions for a more prehensile hallux in western gorillas relative to a more stable, plantigrade hallux in eastern gorillas. The characteristics that distinguish eastern gorilla taxa from one another appear unrelated to hallucial abduction ability or frequency of arboreality. In total, this reexamination of medial cuneiform morphology suggests differentiation between eastern and western gorillas due to a longstanding ecological divergence and more recent and possibly non-adaptive differences between eastern taxa.     

Little Foot and big thoughts—a re-evaluation of the Stw573 foot from Sterkfontein, South Africa

The part of the fossil assemblage Stw573 consisting of some medial foot bones was initially reported by Clarke & Tobias (Science 269 (2002) 521). They found it to have both ape- and human-like qualities, being human-like proximally and ape-like distally. We have undertaken a re-examination of this pedal assemblage using a multivariate analysis; while we also found ape- and human-like qualities, they are in direct conflict with the original findings of Clarke and Tobias. We report an essentially ape-like morphology proximally and a human-like morphology distally; the talus and navicular were found to be ape-like and the medial cuneiform human-like. We also undertook a morphometric analysis of the medial cuneiform from the fossil assemblage OH8, as this was not included in the original OH8 study of Kidd et al (J Hum Evol 31 (1996) 269); this cuneiform was found to have a human-like morphology. Thus, the medial column findings from the two assemblages are very similar. This finding, coupled with the re-evaluation of the stratigraphy at Sterkfontein (Am J Phys Anthrop 119 (2002) 192), suggests that the two may have been contemporaneous.

We also note that three broad patterns of modification have been identified, equating to proximal–distal lateral–medial (cranio–caudal) and dorsal–plantar (posterior–anterior). It has not escaped our notice that these patterns are each controlled by specific genes or growth factors; we thus see a morphometric expression of our developmental past.     

Hallucal tarsometatarsal joint in Australopithecus afarensis

Hallucal tarsometatarsal joints from African pongids, modern humans, and Australopithecus afarensis are compared to investigate the anatomical and mechanical changes that accompanied the transition to terrestrial bipedality. Features analyzed include the articular orientation of the medial cuneiform, curvature of the distal articular surface of the medial cuneiform, and the articular configuration of the hallucal metatarsal proximal joint surface. Morphological characteristics of the hallucal tarsometatarsal joint unequivocally segregate quadrupedal pongids and bipedal hominids.     

In vitro study of foot kinematics using a dynamic walking cadaver model

There is a dearth of information on navicular, cuboid, cuneiform and metatarsal kinematics during walking and our objective was to study the kinematic contributions these bones might make to foot function. A dynamic cadaver model of walking was used to apply forces to cadaver feet and mobilise them in a manner similar to in vivo. Kinematic data were recorded from 13 cadaver feet. Given limitations to the simulation, the data describe what the cadaver feet were capable of in response to the forces applied, rather than exactly how they performed in vivo. The talonavicular joint was more mobile than the calcaneocuboid joint. The range of motion between cuneiforms and navicular was similar to that between talus and navicular. Metatarsals four and five were more mobile relative to the cuboid than metatarsals one, two and three relative to the cuneiforms. This work has confirmed the complexity of rear, mid and forefoot kinematics. The data demonstrate the potential for often-ignored foot joints to contribute significantly to the overall kinematic function of the foot. Previous emphasis on the ankle and sub talar joints as the principal articulating components of the foot has neglected more distal articulations. The results also demonstrate the extent to which the rigid segment assumptions of previous foot kinematics research have over simplified the foot.     

Consideration of digitization precision when building local coordinate axes for a foot model

This study investigated whether points digitized for the purpose of embedding coordinate systems into the foot accurately represented the orientation of the bone described. Eight complete data sets were collected from 9 adult cadaver specimens. Palpable landmarks defined 5 segments to include the calcaneus, navicular, medial cuneiform, first metatarsal, and hallux. With use of the Flock of Birds electromagnetic motion tracking device, a single examiner digitized a minimum of 3 points for each segment. Coordinate definitions followed the right-hand rule, with left-sided data converted to right-sided equivalency. Local axes were created where X projected approximately forward, Y upward, and Z laterally. Matrix transformation computations calculated the angular precision in degrees between coordinates built from points digitized pre- and post-dissection of surface tissues covering bone. The condition of post-dissection was considered the criterion standard for comparison. Change about the X-axis represented the angular precision of the coordinate in the frontal anatomical plane; Y-axis in the transverse plane; Z-axis in the sagittal plane. The calcaneus and navicular coordinate axes changed by an average of <3° across conditions. Mean coordinate angulation of the cuneiform X, Y, Z axes changed by 6.0°, 4.6°, 11.9°, respectively. Change in coordinate angulation was largest for the X-axis at the first metatarsal (48.6°) and hallux (36.5°). A two-way repeated measures ANOVA found a significant interaction between the axis and segment (F=8.87, P=0.00). Tukey post-hoc comparisons indicated the change in coordinate angulation at the X-axis for the cuneiform, metatarsal, and hallux to be significantly different (P <0.05) from the calcaneus and navicular. The X-axis of the first metatarsal and hallux was different from all other axis-segment combinations except for the Z-axis of the cuneiform. Differences in locating landmarks reduced angular precision of the coordinate axes most in the smallest foot segments where points digitized were located close together. We can recommend the proposed landmarks for the calcaneus and navicular segments, but kinematics determined about the coordinate axes for the small sized medial cuneiform, and the long (X) axis for the first metatarsal and hallux have excessive error.     

Variations in the articular facets of the adult cuneiform bones

This study was carried out on 300 adult cuneiform bones (100 each of medial, intermediate and lateral cuneiform bones) for variations in their articular facets. The bones under study are from the Department of Anatomy, University of Jos, Nigeria. In each group, 75 were male and 25 female bones. The difference in the incidence of various patterns of articular facets in the different cuneiform bones between males and females as well as between right and left sides was found to be statistically significant.     

The evolution of the hallucial tarsometatarsal joint in the Anthropoidea

Changes in the hallucial tarsometatarsal joint, which forms the fulcrum for the grasping hallux, have played a significant role in primate evolution. Comparative studies suggest that one of the morphological novelties heralding the attainment of a monkey grade of structure was the incorporation of the prehallux within this joint. Such a joint is found in the extant Ceboidea and, paradoxically, the Hylobatidae. Hallux and prehallux then form a composite distal articular surface; the proximal surface on the medial cuneiform is completed inferomedially by a convex facet for the prehallux. Divergence of the hallux into the attitude of opposition is accompanied by conjunct rotation, screwing these joint components into a stable, close-packed position. Suppression of the prehallux is accompanied by clear osteological indicators — the absence of prehallux facets on the first metatarsal and medial cuneiform. This modification of the joint is a feature of cercopithecoid evolution, and has also occurred in the hominoid line, after divergence of the ancestral gibbons and apparently after the Dryopithecus (Proconsul) stage. The cladistic relationships indicated by these morphological changes are in striking accord with recent results on primate evolution at the molecular level.     

Hallucial convergence in early hominids

There is a richly documented fossil record of the evolutionary transition from ape-sized brains that are less that one-third the size of modern humans through a series of intermediate-sized brains up to the modern range. The first report on the discovery of the foot of the Stw 573 skeleton emphasized the apparent transitional nature of its great toe [Clarke, R.J., Tobias, P.V., 1995. Sterkfontein Member 2 foot bones of the oldest South African hominid. Science 269, pp. 521-524]. The hallux appeared to be intermediate in its divergence between human-like adduction and ape-like abduction. A major part of this evidence is the medial encroachment of the metatarsal I facet on the medial cuneiform. This study quantifies the variability of this feature in extant hominoids and fossil hominids. The results are consistent with the view that all currently known hominids were specialized for bipedality and lacked the ape-like ability to oppose the great toe.     

The Y-chromosome C3* star-cluster attributed to Genghis Khan's descendants is present at high frequency in the Kerey clan from Kazakhstan

To verify the possibility that the Y-chromosome C3* star-cluster attributed to Genghis Khan and his patrilineal descendants is relatively frequent in the Kereys, who are the dominant clan in Kazakhstan and in Central Asia as a whole, polymorphism of the Y-chromosome was studied in Kazakhs, represented mostly by members of the Kerey clan. The Kereys showed the highest frequency (76.5%) of individuals carrying the Y-chromosome variant known as C3* star-cluster ascribed to the descendants of Genghis Khan. C3* star-cluster haplotypes were found in two subclans, Abakh-Kereys and Ashmaily-Kereys, diverged about 20-22 generations ago according to the historical data. Median network of the Kerey star-cluster haplotypes at 17 STR loci displays a bipartite structure, with two subclusters defined by the only difference at the DYS448 locus. Noteworthy is a strong correspondence of these subclusters with the Kerey subclans affiliation. The data obtained suggest that the Kerey clan appears to be the largest known clan in the world descending from a common Y-chromosome ancestor. Possible ways of Genghis Khan's relationship to the Kereys are discussed.     

Vulnerability Analysis and Passenger Source Prediction in Urban Rail Transit Networks

Based on large-scale human mobility data collected in San Francisco and Boston, the morning peak urban rail transit (URT) ODs (origin-destination matrix) were estimated and the most vulnerable URT segments, those capable of causing the largest service interruptions, were identified. In both URT networks, a few highly vulnerable segments were observed. For this small group of vital segments, the impact of failure must be carefully evaluated. A bipartite URT usage network was developed and used to determine the inherent connections between urban rail transits and their passengers'' travel demands. Although passengers'' origins and destinations were easy to locate for a large number of URT segments, a few show very complicated spatial distributions. Based on the bipartite URT usage network, a new layer of the understanding of a URT segment''s vulnerability can be achieved by taking the difficulty of addressing the failure of a given segment into account. Two proof-of-concept cases are described here: Possible transfer of passenger flow to the road network is here predicted in the cases of failures of two representative URT segments in San Francisco.     

Balanced translocations involving chromosome 12: report of a case and possible evidence for position effect.

A girl with mental retardation, a convulsive disorder and clinical findings resembling cerebral palsy had an apparently balanced 12/18 translocation. Three additional cases reported in the literature had an abnormal phenotype associated with the positioning of segments from other autosomes adjacent to the band 12q21. Penotype abnormalities were not present in 14 individuals in which the translocation involved breaks at other sites on chromosome no. 12. These findings suggest the possibility of a position effect on chromosome segments translocated adjacent to the region 12q21.     

In vivo chromosomal instability in ataxia-telangiectasia homozygotes and heterozygotes

Summary The exfoliated cell micronucleus test was used to monitor in vivo chromosomal instability in a population comprised of five ataxia-telangiectasia (A-T) homozygotes and seven obligate heterozygotes (parents of A-T patients). This assay was previously validated as a procedure for quantifying non-invasively carcinogen-induced chromosomal aberrations occurring in vivo in epithelial tissues of both the oral cavity and the urinary bladder. The procedure involved taking airdried smears of three sites in the oral cavity of each examined individual. Desquamated urinary bladder cells were collected by centrifugation of freshly voided urine samples. Frequencies of exfoliated cells in these preparations were determined and compared with control values (individuals with no genetic chromosomal instability and no known carcinogene exposure) for these sites. Exforliated cell micronucleus (MEC) frequencies were elevated 5- to 14-fold in samples from the A-T homozygotes. This elevation in MEC frequency occurred for both the oral cavity and urinary bladder. Five out of the seven obligate A-T heterozygotes had an elevated MEC frequency in samples from the oral cavity. In addition, all examined urine samples from A-T heterozygotes contained an elevated percentage of micronucleated cells. These data suggest that this assay is suitable for in vivo monitoring of groups of individuals in which genetically produced chromosomal damage occurs. The possibility of A-T heterozygote detection with this simple procedure is of particular significance, since such individuals are believed to comprise up to 1% of the general population, and have been identified as being at elevated risk for cancer.     

Flexible interaction of Drosophila Smad complexes with bipartite binding sites

A subset of BMP-responsive enhancer elements are characterized by pairing of a GC-rich Smad1 binding site and an SBE-type Smad4 binding site. Such paired, or bipartite, sites are in some cases just 5 bp apart and thus might be contacted by a single Smad1-Smad4 complex. Other potential pairings are separated as much as 60 bp but it is not known whether such longer distances can be spanned by a Smad1-Smad4 complex, indeed binding of native Smad1-Smad4 complexes to any of these bipartite elements has yet to be reported. Here we report that a complex of the homologous Drosophila Smad proteins, Mad and Medea, is capable of concerted binding to GC-rich and SBE sites separated by as much as 20 bp. The wider the separation, the more severely binding affinity was reduced by shortening of the linker region that tethers the DNA binding domain of Medea. In contrast, length of the Mad linker did not affect the allowed distance between paired sites, rather it contributes specifically to Mad contact with the GC-rich site. Finally, we show that Smad1 and Smad4 can participate in binding to bipartite sites.     

Chromosomal illegitimate recombination in mammalian cells is associated with intrinsically bent DNA elements.

Illegitimate recombination is the most frequent mechanism for chromosomal rearrangements in mammalian cells, yet little is known about this process. Most of the studies to date have looked at the sequences present at illegitimate junctions. These revealed the presence of recurrent DNA motifs, none of which was consistently found. We have undertaken to determine if intrinsic DNA structures such as bent DNA elements could be a major determinant in chromosomal illegitimate recombination. Using a two dimensional electrophoretic assay we found that eight out of eight junctions, resulting from various types of chromosomal rearrangements, had migration behaviour characteristic of DNA containing intrinsically bent DNA elements. In all cases, these occurred within one kilobase of the junctions, and in most cases could be found in both participating DNA segments. We also found that these bent DNA elements were present before the recombination event. When we analysed the frequency of intrinsically bent DNA elements in random chromosomal fragments, we found it to be about one per 11 kilobases. Thus these results suggest that bent DNA is associated with chromosomal illegitimate recombination.     

The Interplay between Natural Selection and Susceptibility to Melanoma on Allele 374F of SLC45A2 Gene in a South European Population

We aimed to study the selective pressures interacting on SLC45A2 to investigate the interplay between selection and susceptibility to disease. Thus, we enrolled 500 volunteers from a geographically limited population (Basques from the North of Spain) and by resequencing the whole coding region and intron 5 of the 34 most and the 34 least pigmented individuals according to the reflectance distribution, we observed that the polymorphism Leu374Phe (L374F, rs16891982) was statistically associated with skin color variability within this sample. In particular, allele 374F was significantly more frequent among the individuals with lighter skin. Further genotyping an independent set of 558 individuals of a geographically wider population with known ancestry in the Spanish population also revealed that the frequency of L374F was significantly correlated with the incident UV radiation intensity. Selection tests suggest that allele 374F is being positively selected in South Europeans, thus indicating that depigmentation is an adaptive process. Interestingly, by genotyping 119 melanoma samples, we show that this variant is also associated with an increased susceptibility to melanoma in our populations. The ultimate driving force for this adaptation is unknown, but it is compatible with the vitamin D hypothesis. This shows that molecular evolution analysis can be used as a useful technology to predict phenotypic and biomedical consequences in humans.     

Mitochondrial Mutations in Subjects with Psychiatric Disorders

A considerable body of evidence supports the role of mitochondrial dysfunction in psychiatric disorders and mitochondrial DNA (mtDNA) mutations are known to alter brain energy metabolism, neurotransmission, and cause neurodegenerative disorders. Genetic studies focusing on common nuclear genome variants associated with these disorders have produced genome wide significant results but those studies have not directly studied mtDNA variants. The purpose of this study is to investigate, using next generation sequencing, the involvement of mtDNA variation in bipolar disorder, schizophrenia, major depressive disorder, and methamphetamine use. MtDNA extracted from multiple brain regions and blood were sequenced (121 mtDNA samples with an average of 8,800x coverage) and compared to an electronic database containing 26,850 mtDNA genomes. We confirmed novel and rare variants, and confirmed next generation sequencing error hotspots by traditional sequencing and genotyping methods. We observed a significant increase of non-synonymous mutations found in individuals with schizophrenia. Novel and rare non-synonymous mutations were found in psychiatric cases in mtDNA genes: ND6, ATP6, CYTB, and ND2. We also observed mtDNA heteroplasmy in brain at a locus previously associated with schizophrenia (T16519C). Large differences in heteroplasmy levels across brain regions within subjects suggest that somatic mutations accumulate differentially in brain regions. Finally, multiplasmy, a heteroplasmic measure of repeat length, was observed in brain from selective cases at a higher frequency than controls. These results offer support for increased rates of mtDNA substitutions in schizophrenia shown in our prior results. The variable levels of heteroplasmic/multiplasmic somatic mutations that occur in brain may be indicators of genetic instability in mtDNA.     

上海,无锡地区汉族人群HLADR4基因14种亚型分析

本文应用聚合酶链反应配合限制性内切酶片段长度多态性（ＰＣＲ－ＲＦＬＰ）分析方法,在１３０例上海、无锡地区汉族人群中发现２３例ＤＲ４基因检测呈阳性,对其ＤＲ４基因的亚型ＲＦＬＰ和分布频率特征进行了研究,结果显示,ＤＲ４基因携带者为１７．７％,存在７种ＤＲ４亚型,以ＤＲＢ１＊０４０５频率最高,构成ＤＲ４阳性人群的４７．８％,其次为ＤＲＢ１＊０４０６和ＤＲＢ１＊０４０３,分别为２１．７％和１７．４％,上     

Biomechanics of the joints of the large toe. Shape and movement of the first tarsometatarsal joint and of the medial cuneonavicular joint]

90% of the first (hallucal) tarsometatarsal joints are screw-shaped; the axis is directed upwards to the front touching the lateral edge of the joint. Thus the plantar flexion is inevitably accompanied by an adduction and a pronation, and vice versa a dorsiflexion is consequently accompanied by an abduction and a supination, when the articular surfaces exactly slide along each other. 10% of these joints, however, are ellipsoid-shaped; in this case the distal articular surface of the medial cuneiform bone has the form of an ovoid head, and a strong ligament situated next to the lateral edge of the joint effects the same kind of motion described above. The medial cuneonavicular joint is always ellipsoid-shaped, the head of which is made up by the medial facet of the distal articular surface of the navicular bone. Each of the two joints mentioned has a considerable range of mobility.     

Genetic and environmental components of chiasma control

Variation in chiasma frequency within and between individuals has been investigated in Schistocerca gregaria and Stethophyma grossum. By taking sequential samples of the same testis in S. gregaria it has been demonstrated that there is considerable variation in chiasma frequency between times, within individuals, and that this variation is not evenly distributed between individuals of the same population. The response and recovery patterns after exposure to successive temperature treatments also indicate a differential sensitivity of individuals within the experimental population. — An analysis of interfollicular variation in chiasma frequency has revealed significant differences between follicles within individuals both in S. gregaria and a Spanish population of S. grossum. A comparable analysis on individuals of S. grossum carrying supernumerary segments shows that the presence of such segments increases the amount of variation between follicles within individuals and also between individuals within the population. — The distribution of cell chiasma frequencies in S. gregaria is normal whereas in Stethophyma cell frequencies approximate to a Poisson distribution. The structurally different supernumerary segments, present in Austrian and Spanish populations of S. grossum, both increase mean chiasma frequency and they modify the between cell variance in different ways — the former interchromosomally and the latter intrachromosomally. — The differences in chiasma frequency between follicles and between times within individuals and the differential reaction to heat shock reflect differences in the pattern of genotype-environment interaction. Similarly it can be argued that the presence of polymorphisms involving supernumerary material may play an equivalent role by increasing the between cell or between bivalent variance within individuals, a unique form of genotype-environment interaction at the endophenotypic level. — Such variation in genotype sensitivity to environmental modification has important adaptive value especially in organisms which are subject to recurrent, often random, changes in their environment.