Changes in metatarsal robusticity following experimental surgery

When a marginal metatarsal (M1 or M5) is amputated in neonatal rats, robusticity increases in all other metatarsals in both sexes. The robusticity increase is greatest in the metatarsal adjacent to the operation and declines in the direction away from it. The tripod structure of the rat's foot with its maximum robusticity of the marginal metatarsals is retained. When both marginal metatarsals are removed, this tripod arrangement is less clearly retained. When robusticity of all remaining metatarsals is averaged in a total robusticity quotient, total robusticity increase is greater in M1 than in M5 removal and greatest when both are removed. Total increase is greater in females than in males. Metatarsal robusticity increases result from retardation of longitudinal growth and increase of weight. The fact that some robusticity increases coincide with lesser length but not with increased weight suggests that in the process of robusticity increase longitudinal growth retardation precedes that of weight increase. Lesser length and greater weight of a long bone occurs also when hypofunction is produced in neonatal rats. However, in hypofunction the thickness of the compacta is increased leading to an obliteration of the medullary canal, while in the experimental metatarsals of this study, submitted to greater weight-bearing stresses, this canal is never reduced or obliterated.     

Metatarsal robusticity in primates and a few other plantigrade mammals

By using a new technique for determining relative metatarsal robusticity, the distribution of the 1+5 pattern (in which M5 is the second most robust metatarsal after M1) and 15 pattern (in which M5 is the least robust of all metatarsals) was established in primates and a few other plantigrade mammals. The first pattern is associated with a terrestrial and the second with an arboreal substrate. Robusticity formulae are not connected with specific locomotor patterns, but a total robusticity quotient is associated with these patterns and substrate preference as well. Changes in substrate preference are accompanied by changes of total robusticity, an increased number of permutations and ultimately a change of the robusticity pattern. Intermetatarsal robusticity gradients are related to the direction and intensity of muscular activity. A combined analysis of all factors can reveal a great deal of the locomotor history of a taxon.Also ofThe Institute of Applied Biology, New York.     

Volumetric determination of metatarsal robusticity in a few living primates and in the foot ofOreopithecus

A new technique is described for the volumetric determination of metatarsal robusticity. Since volume was substituted for weight of a previously used technique, that technique is applicable to fossilized material. The comparability between the metric and volumetric techniques was tested and found to be sufficiently close to make the two techniques interchangeable. When the volumetric technique was applied to fourOreopithecus metatarsals, their robusticity was found to follow the 1→5 pattern (in which M5 is the least robust metatarsal), a pattern typical for all higher primates but present also inHomo. Their total robusticity was found to be closest toHomo and the gorilla, suggesting the likelihood of a terrestrial habitat forOreopithecus.     

Implications of relative robusticity in the Olduvai metatarsus

The relative robusticity of the metatarsals in OH-8 is reviewed in light of the normal variation in metatarsal robusticity in Pan and Homo. The pattern in OH-8 is found to be fully commensurate with a striding gait.     

Differences in foot contact times between obese and non-obese postmenopausal women when crossing obstacles

Abstract

Objective: This study aimed to investigate the foot contact time differences between obese and non-obese subjects during walking when crossing obstacles.

Methods: Ninety-eight postmenopausal women were assigned to four groups, and their plantar pressure temporal data were collected using a two-step protocol during walking when crossing an obstacle set at 30% height of lower limb length of each subject. The initial, final, and duration of contact of 10?foot areas were measured.

Results: Leading limb: (1) the heel groups initiated foot contact using the heel, and the non-heel groups initiated contact using the metatarsals; (2) heel obese subjects showed an earlier initial contact and a longer contact duration of metatarsals 2–3; (3) non-heel obese subjects showed an earlier midfoot initial contact. Regarding the trailing limb: (4) heel obese subjects showed an earlier midfoot initial contact and a longer contact duration of metatarsal 5; (5) non-heel obese subjects showed an earlier initial contact and a longer contact duration of metatarsals 4–5.

Conclusions: (1) The non-heel groups’ foot rollover pattern may result from an attempt of rapidly restoring stability; (2) the heel obese subjects seem to regulate their plantar foot muscles to overcome their overweight; (3) the overweight of the non-heel obese subjects leads to a quicker backward foot roll-over from the metatarsals to the heel; (4) the overweight of the heel obese subjects can distort their footprints and/or their higher inertia may precipitate an anticipation of the midfoot contact, which can also explain the result observed for 5.     

Hand use and metacarpal robusticity in Catarrhini

Recent studies,Rightmire (1972) andDay andScheuer (1973), have investigated the affinities of early hominid metacarpals from Swartkrans. Because of its extensive use in the analysis of metatarsals, the index of robusticity has also been applied to some fossil metacarpals. From the metatarsal analyses, it has been shown that within a group a variety of robusticity patterns exist with the average pattern occuring approximately 50 per cent of the time. This, coupled with the fact that it has also been shown that within the order Primates the pattern is not necessarily diagnostic of any locomotor category, has led us to investigate the usefulness of such an index in assessing primate metacarpals. In this study, metacarpal robusticity patterns and the Total Robusticity Quotient are established for seven cercopithecoid genera and the results correlated with hand use. It is found that although patterns of robusticity are not diagnostic of locomotor categories, the TRQ relates well to hand use: low TRQ's are found in primates which use their hands to walk on a flat substrate, while high TRQ's are diagnostic of arm swinging animals. Primates with reduced thumb use in a precision grip and little manipulative use of the hand have higher TRQ's than those with a good precision grip. The model derived from our sample of Cercopithecoidea is tested with a hominoid sample of four genera and found to be similarly applicable.     

Olduvai Hominin 8 foot pathology: A comparative study attempting a differential diagnosis

Olduvai Hominin (OH) 8, a 1.76 million year old left foot skeleton, has osteophytic lipping on the metatarsal bases, which when compared to a modern sample, may help paleoanthropologists determine whether the foot bones represent an injured subadult or an osteoarthritic adult. This study compares the OH 8 lipping pattern to those of 140 individual Amerindians comprising four different age classes to determine whether the OH 8 lipping is likely to be age-related osteoarthritis. OH 8 metatarsal lipping followed a pattern similar to that determined in the comparative sample to be age-related osteoarthritis. Similarities include metatarsal base lipping that is frequently located on the dorsal surface, metatarsal base lipping that is more severe on the lateral metatarsals compared to the medial metatarsals, and the presence of a pseudojoint between metatarsal 1 and metatarsal 2. The chance of finding an individual with osteoarthritis lipping increases from 3.45% in the age group 18–22 years to 55% in individuals over 35 years. The chance of finding a pseudojoint increases from 1.32% in non-osteoarthritic individuals to 15.15% in individuals with osteoarthritis. Results from this study indicate that the OH 8 foot bones are most likely from an adult and more likely to belong to Paranthropus boisei, the skull of which was found in the same excavations with OH 8, than to the juvenile Homo habilis holotype.     

Error in the description of foot kinematics due to violation of rigid body assumptions

Kinematic data from rigid segment foot models inevitably includes errors because the bones within each segment move relative to each other. This study sought to define error in foot kinematic data due to violation of the rigid segment assumption. The research compared kinematic data from 17 different mid and forefoot rigid segment models to kinematic data of the individual bones comprising these segments. Kinematic data from a previous dynamic cadaver model study was used to derive individual bone as well as foot segment kinematics.Mean and maximum errors due to violation of the rigid body assumption varied greatly between models. The model with least error was the combination of navicular and cuboid (mean errors <=1.3°, average maximum error <=2.4°). Greatest error was seen for the model combining all the ten bones (mean errors <=4.4°, average maximum errors <=6.9°). Based on the errors reported a three segment mid and forefoot model is proposed: (1) Navicular and cuboid, (2) cuneiforms and metatarsals 1, 2 and 3, and (3) metatarsals 4 and 5. However the utility of this model will depend on the precise purpose of the in vivo foot kinematics research study being undertaken.     

Foot kinematics during walking measured using bone and surface mounted markers

The aim was to compare kinematic data from an experimental foot model comprising four segments ((i) heel, (ii) navicular/cuboid (iii) medial forefoot, (iv) lateral forefoot), to the kinematics of the individual bones comprising each segment. The foot model was represented using two different marker attachment protocols: (a) markers attached directly to the skin; (b) markers attached to rigid plates mounted on the skin. Bone data were collected for the tibia, talus, calcaneus, navicular, cuboid, medial cuneiform and first and fifth metatarsals (n=6). Based on the mean differences between the three data sets during stance, the differences between any two of the three kinematic protocols (i.e. bone vs skin, bone vs plate, skin vs plate) were >3 degrees in only 35% of the data and >5 degrees in only 3.5% of the data. However, the maximum difference between any two of the three protocols during stance was >3 degrees in 100% of the data, >5 degrees in 73% of the data and >8 degrees in 23% of the data. Differences were greatest for motion of the combined navicular/cuboid relative to the calcaneus and the medial forefoot segment relative to the navicular/cuboid. The differences between the data from the skin and plate protocols were consistently smaller than differences between either protocol and the kinematic data for each bone comprising the segment. The pattern of differences between skin and plate protocols and the actual bone motion showed no systematic pattern. It is unlikely that one rigid body foot model and marker attachment approach is always preferable over another.     

The cross-sectional geometry of the hand and foot bones of the hominoidea and its relationship to locomotor behavior

Cheiridia are valuable indicators of positional behavior, as they directly contact the substrate, but systematic comparison of the structural properties of both metacarpals and metatarsals has never been carried out. Differences in locomotor behavior among the great apes (knuckle-walking vs. quadrumanous climbing) can produce biomechanical differences that may be elucidated by the parallel study of cross-sectional characteristics of metacarpals and metatarsals. The aim of this work is to study the cross-sectional geometric properties of these bones and their correlation with locomotor behavior in large-bodied hominoids. The comparisons between bending moments of metacarpals and metatarsals of the same ray furnished interesting results. Metacarpals III and especially IV of the knuckle-walking African apes were relatively stronger than those of humans and orangutans, and metatarsal V of humans was relatively stronger than those of the great apes. Interestingly, the relative robusticity of the metacarpal IV of the quadrumanous orangutan was between that of the African apes and that of humans. The main conclusions of the study are: 1) cross-sectional dimensions of metacarpals and metatarsals are influenced by locomotor modes in great apes and humans; 2) interlimb comparisons of cross-sectional properties of metacarpals and metatarsals are good indicators of locomotor modes in great apes and humans; and 3) the results of this study are in accord with those of previous analyses of plantar pressure and morphofunctional traits of the same bones, and with behavioral studies. These results provide a data base from which it will be possible to compare the morphology of the fossils in order to gain insight into the locomotor repertoires of extinct taxa.     

Mining Pure,Strict Epistatic Interactions from High-Dimensional Datasets: Ameliorating the Curse of Dimensionality

Background

The interaction between loci to affect phenotype is called epistasis. It is strict epistasis if no proper subset of the interacting loci exhibits a marginal effect. For many diseases, it is likely that unknown epistatic interactions affect disease susceptibility. A difficulty when mining epistatic interactions from high-dimensional datasets concerns the curse of dimensionality. There are too many combinations of SNPs to perform an exhaustive search. A method that could locate strict epistasis without an exhaustive search can be considered the brass ring of methods for analyzing high-dimensional datasets.

Methodology/Findings

A SNP pattern is a Bayesian network representing SNP-disease relationships. The Bayesian score for a SNP pattern is the probability of the data given the pattern, and has been used to learn SNP patterns. We identified a bound for the score of a SNP pattern. The bound provides an upper limit on the Bayesian score of any pattern that could be obtained by expanding a given pattern. We felt that the bound might enable the data to say something about the promise of expanding a 1-SNP pattern even when there are no marginal effects. We tested the bound using simulated datasets and semi-synthetic high-dimensional datasets obtained from GWAS datasets. We found that the bound was able to dramatically reduce the search time for strict epistasis. Using an Alzheimer''s dataset, we showed that it is possible to discover an interaction involving the APOE gene based on its score because of its large marginal effect, but that the bound is most effective at discovering interactions without marginal effects.

Conclusions/Significance

We conclude that the bound appears to ameliorate the curse of dimensionality in high-dimensional datasets. This is a very consequential result and could be pivotal in our efforts to reveal the dark matter of genetic disease risk from high-dimensional datasets.     

Heterochronic mechanisms of morphological diversification and evolutionary change in the neotropical salamander,Bolitoglossa occidentalis (Amphibia: Plethodontidae)

Bolitoglossa occidentalis, a lowland salamander of Mexico and Guatemala, has a highly derived morphology. The features that are derived with respect to the condition in generalized members of the genus include the following: (1) small body size; (2) short tail; (3) fully webbed hands and feet; (4) reduction and loss of certain phalangeal elements; (5) fusion of carpals and tarsals; (6) absence of prefrontal bones; and (7) reduced skull ossification. The ontogeny of this species was analyzed quantitatively and compared with the patterns of growth and differentiation encountered in two morphologically generalized members of the genus, B. rostrata and B. subpalmata. Most of the derived features can be explained by invoking a single heterochronic process: truncation of development at a small size (most likely the product of early maturation). Therefore, B. occidentalis is a paedomorphic species whose morphology has been attained through the process of progenesis. This result supports Alberch's ('80a) prediction, based on functional analysis, that the principle adaptation to arboreality in B. occidentalis is small size; other derived morphological features are associated with the organism's truncated development and may have no adaptive significance. However, patterns of dissociation are found within this overall progenetic process. Some of these include the following: (1) accelerated growth rates of the metatarsals and first phalanges, and retarded growth rates of the second and third phalangeal elements; (2) dissociation between rates of ossification of the skull and the autopodial elements; and (3) dissociation between the timing of termination of the process of shape change during the ontogeny of the foot (the product of differential growth between digital and interdigital areas) and termination of growth in overall foot size (foot surface area). This later result illustrates the independence of morphogenetic phenomena (shape change) from processes of growth (size increase).     

The relative lengths and weights of metacarpals and metatarsals in baboons (papio hamadryas)

The lengths and weights of metacarpals and metatarsals were measured in two collections of baboon skeletons-33 animals, all born and raised in the wild, and 60 animals, nearly all born and raised in captivity. For both length and weight, ratios were constructed for all possible pairings of the five bones in each individual hand and foot. The pattern of results was not identical for the two collections, but substantial sex differences existed in both collections for many of the ratios calculated. Nearly all of the large sex differences were in the direction of the length or weight ratio being smaller for males than for females. For the length ratios showing the largest sex differences, those differences were larger for the right hand than for the left, and larger for the left foot than for the right, but this pattern was less evident for the weight ratios. Some length ratios for human fingers show sex differences of the sort seen in the metacarpals and metatarsals of these baboons, and the human differences in relative length exist early in life. The implication is that the marked sex difference in androgen exposure during prenatal development may effect the relative size of the individual bones of the extremities in male and female humans and baboons. The relative sizes of the bones of the hand and foot may provide helpful supplemental information on the relations between species, thus making the study of hand and foot bones in other primates and mammals worthwhile.     

Key Features of Human Episodic Recollection in the Cross-Episode Retrieval of Rat Hippocampus Representations of Space

Neurophysiological studies focus on memory retrieval as a reproduction of what was experienced and have established that neural discharge is replayed to express memory. However, cognitive psychology has established that recollection is not a verbatim replay of stored information. Recollection is constructive, the product of memory retrieval cues, the information stored in memory, and the subject''s state of mind. We discovered key features of constructive recollection embedded in the rat CA1 ensemble discharge during an active avoidance task. Rats learned two task variants, one with the arena stable, the other with it rotating; each variant defined a distinct behavioral episode. During the rotating episode, the ensemble discharge of CA1 principal neurons was dynamically organized to concurrently represent space in two distinct codes. The code for spatial reference frame switched rapidly between representing the rat''s current location in either the stationary spatial frame of the room or the rotating frame of the arena. The code for task variant switched less frequently between a representation of the current rotating episode and the stable episode from the rat''s past. The characteristics and interplay of these two hippocampal codes revealed three key properties of constructive recollection. (1) Although the ensemble representations of the stable and rotating episodes were distinct, ensemble discharge during rotation occasionally resembled the stable condition, demonstrating cross-episode retrieval of the representation of the remote, stable episode. (2) This cross-episode retrieval at the level of the code for task variant was more likely when the rotating arena was about to match its orientation in the stable episode. (3) The likelihood of cross-episode retrieval was influenced by preretrieval information that was signaled at the level of the code for spatial reference frame. Thus key features of episodic recollection manifest in rat hippocampal representations of space.     

Reverse flow instep island flap.

The retrogradely perfused medial plantar artery flap was used in a leprosy patient with a plantar ulcer over the heads of the second and third metatarsals. The flap is based on the anastomosis of the medial plantar artery with the branch of the first plantar metatarsal artery, which supplies the medial side of the great toe. This design provides reconstruction with like local tissues while not distorting the weight-bearing pattern of the foot.     

Prediction of peak pressure from clinical and radiological measurements in patients with diabetes

Background

Various structural and functional factors of foot function have been associated with high local plantar pressures. The therapist focuses on these features which are thought to be responsible for plantar ulceration in patients with diabetes. Risk assessment of the diabetic foot would be made easier if locally elevated plantar pressure could be indicated with a minimum set of clinical measures.

Methods

Ninety three patients were evaluated through vascular, orthopaedic, neurological and radiological assessment. A pressure platform was used to quantify the barefoot peak pressure for six forefoot regions: big toe (BT) and metatarsals one (MT-1) to five (MT-5). Stepwise regression modelling was performed to determine which set of the clinical and radiological measures explained most variability in local barefoot plantar peak pressure in each of the six forefoot regions. Comprehensive models were computed with independent variables from the clinical and radiological measurements. The difference between the actual plantar pressure and the predicted value was examined through Bland-Altman analysis.

Results

Forefoot pressures were significant higher in patients with neuropathy, compared to patients without neuropathy for the whole forefoot, the MT-1 region and the MT-5 region (respectively 138 kPa, 173 kPa and 88 kPa higher: mean difference). The clinical models explained up to 39 percent of the variance in local peak pressures. Callus formation and toe deformity were identified as relevant clinical predictors for all forefoot regions. Regression models with radiological variables explained about 26 percent of the variance in local peak pressures. For most regions the combination of clinical and radiological variables resulted in a higher explained variance. The Bland and Altman analysis showed a major discrepancy between the predicted and the actual peak pressure values.

Conclusion

At best, clinical and radiological measurements could only explain about 34 percent of the variance in local barefoot peak pressure in this population of diabetic patients. The prediction models constructed with linear regression are not useful in clinical practice because of considerable underestimation of high plantar pressure values. Identification of elevated plantar pressure without equipment for quantification of plantar pressure is inadequate. The use of quantitative plantar pressure measurement for diabetic foot screening is therefore advocated.     

Perichondrial expression of Wdr5 regulates chondrocyte proliferation and differentiation

Wdr5 is developmentally expressed in osteoblasts and is required for osteoblast differentiation. Mice overexpressing Wdr5 under the control of the mouse α(1)I collagen promoter (Col I-Wdr5) display accelerated osteoblast differentiation as well as accelerated chondrocyte differentiation, suggesting that overexpression of Wdr5 in osteoblasts affects chondrocyte differentiation. To elucidate the molecular mechanism by which overexpression of Wdr5 in the perichondrium regulates chondrocyte differentiation, studies were undertaken using skeletal elements and cultured metatarsals isolated from wild-type and Col I-Wdr5 embryos. FGF18 mRNA levels were decreased in Col I-Wdr5 humeri. Furthermore, local delivery of FGF18 to the bone collar of ex vivo cultures of metatarsals attenuated the chondrocyte phenotype of the Col I-Wdr5 metatarsals. Impairing local FGF action in wild-type metatarsals resulted in a chondrocyte phenotype analogous to that of Col I-Wdr5 metatarsals implicating impaired FGF action as the cause of the phenotype observed. The expression of Twist-1, which regulates chondrocyte differentiation, was increased in Col I-Wdr5 humeri. Chromatin immunoprecipitation analyses demonstrated that Wdr5 is recruited to the Twist-1 promoter. These findings support a model in which overexpression of Wdr5 in the perichondrium promotes chondrocyte differentiation by modulating the expression of Twist-1 and FGF18.     

Metatarsal fusion pattern and developmental morphology of the Olduvai Hominid 8 foot: Evidence of adolescence

The morphology of the Olduvai Hominid (OH) 8 foot and the sequence of metatarsal epiphyseal fusion in modern humans and chimpanzees support the hypothesis that OH 8 belonged to an individual of approximately the same relative age as the OH 7 subadult, the holotype of Homo habilis. Modern humans and chimpanzees exhibit a variety of metatarsal epiphyseal fusion patterns, including one identical to that observed in OH 8 in which metatarsal 1 fuses before metatarsals 2-5. More than the metatarsal fusion sequence, however, the principal evidence of the youthful age of OH 8 lies in the morphology of metatarsals 1, 2, and 3. Because both OH 8 and OH 7 come from the same stratum at the FLK NN type site, the most parsimonious explanation of the OH 8 and OH 7 data is that this material belonged to the same individual, as originally proposed by Louis Leakey. The proposition that OH 8 belonged to an adult is unsupported by morphology, including radiographic evidence, and the fusion sequences in human and chimpanzee skeletal material reported here and in the literature.     

Omega-3 deficiency and neurodegeneration in the substantia nigra: Involvement of increased nitric oxide production and reduced BDNF expression

Background

Our previous study demonstrated that essential fatty acid (EFA) dietary restriction over two generations induced midbrain dopaminergic cell loss and oxidative stress in the substantia nigra (SN) but not in the striatum of young rats. In the present study we hypothesized that omega-3 deficiency until adulthood would reduce striatum's resilience, increase nitric oxide (NO) levels and the number of BDNF-expressing neurons, both potential mechanisms involved in SN neurodegeneration.

Methods

Second generation rats were raised from gestation on control or EFA-restricted diets until young or adulthood. Lipoperoxidation, NO content, total superoxide dismutase (t-SOD) and catalase enzymatic activities were assessed in the SN and striatum. The number of tyrosine hydroxylase (TH)- and BDNF-expressing neurons was analyzed in the SN.

Results

Increased NO levels were observed in the striatum of both young and adult EFA-deficient animals but not in the SN, despite a similar omega-3 depletion (~ 65%) in these regions. Increased lipoperoxidation and decreased catalase activity were found in both regions, while lower tSOD activity was observed only in the striatum. Fewer TH- (~ 40%) and BDNF-positive cells (~ 20%) were detected at the SN compared to the control.

Conclusion

The present findings demonstrate a differential effect of omega-3 deficiency on NO production in the rat's nigrostriatal system. Prolonging omega-3 depletion until adulthood impaired striatum's anti-oxidant resources and BDNF distribution in the SN, worsening dopaminergic cell degeneration.

General significance

Omega-3 deficiency can reduce the nigrostriatal system's ability to maintain homeostasis under oxidative conditions, which may enhance the risk of Parkinson's disease.