Hunter-gatherer genomic diversity suggests a southern African origin for modern humans.

Africa is inferred to be the continent of origin for all modern human populations, but the details of human prehistory and evolution in Africa remain largely obscure owing to the complex histories of hundreds of distinct populations. We present data for more than 580,000 SNPs for several hunter-gatherer populations: the Hadza and Sandawe of Tanzania, and the ≠Khomani Bushmen of South Africa, including speakers of the nearly extinct N|u language. We find that African hunter-gatherer populations today remain highly differentiated, encompassing major components of variation that are not found in other African populations. Hunter-gatherer populations also tend to have the lowest levels of genome-wide linkage disequilibrium among 27 African populations. We analyzed geographic patterns of linkage disequilibrium and population differentiation, as measured by F(ST), in Africa. The observed patterns are consistent with an origin of modern humans in southern Africa rather than eastern Africa, as is generally assumed. Additionally, genetic variation in African hunter-gatherer populations has been significantly affected by interaction with farmers and herders over the past 5,000 y, through both severe population bottlenecks and sex-biased migration. However, African hunter-gatherer populations continue to maintain the highest levels of genetic diversity in the world.

Two human tyrosine tRNA genes contain introns.

A human lambda-phage recombinant which contains at least four tRNA genes, has been isolated. Two DNA fragments were subcloned to give the recombinant plasmids pM6 and pM6128. Nucleotide sequence analysis showed that each plasmid contained a different tyrosine acceptor tRNA (tRNATyr) gene. Both tRNATyr genes are interrupted by 21-bp introns. These recombinant plasmids have been shown to direct the in vitro synthesis of tRNA-sized products in a HeLa cell transcription system.

Cloning and analysis of five mitochondrial tRNA-encoding genes from the fungus Beauveria bassiana.

Five mitochondrial (mt) tRNA genes from the filamentous fungus, Beauveria bassiana, were cloned and sequenced. The genes encoding the Val-, Ile-, Ser-, Trp- and Pro-accepting tRNAs were found clustered in the region 5' to the lrRNA-encoding gene. The genes were 64-77% homologous with the equivalent genes from other filamentous fungi, 49-58% to yeasts with the exception of the Val-accepting tRNA-encoding gene which was 76%, and only slightly homologous with Escherichia coli. The B. bassiana mt genetic code was found to be similar to that of other fungal mitochondria in that the UGA codon is used as a signal for Trp rather than as a stop codon. Transcript analysis has revealed that the genes present in tRNA cluster are transcribed and processed into tRNA-size products. Secondary structure models proposed for the gene products show that conservation of tRNA secondary structure also exists. The presence of a GGC sequence rather than a GGU sequence in the D-loop of the tRNA(Trp)-encoding gene is a feature unique to the B. bassiana mt tRNA. An unconventional G-A base pair present in the D-stem of the tRNA(Ser)-encoding gene is a feature conserved in the mt tRNA of other filamentous fungi. Comparison of the B. bassiana tRNA-encoding genes with those of two other filamentous fungi and two yeasts revealed that the differences between closely related species favoured transition-type mutations.

Stance and balance following bilateral labyrinthectomy.

Although vestibular input codes head acceleration, it is not clear whether or not this signal is critical for triggering the initial postural response to a perturbation of stance, and for determining the appropriate direction of response. These experiments were designed to examine the contribution of vestibular inputs to the control of balance in the freely standing cat. Four cats were trained to stand quietly on a moveable force platform. The animal's stance was unexpected perturbed by applying a linear ramp-and-hold translation to the support surface in each of eight different directions in the horizontal plane. The characteristics of quiet stance and the response to the perturbations were quantified in terms of the 3-D ground reaction forces under each paw and the EMG activity in selected muscles. The animals were bilaterally labyrinthectomized, and their responses compared before and after lesion. The cats were able to stand stably on the platform within 2-3 days of the lesion. During quiet stance, there was no change in the distribution of vertical forces under the paws and no increase in sway area. Horizontal plane forces, which were normally outwardly directed on the diagonals, became more laterally directed and transiently larger in amplitude. The level of tonic EMG activity increased in some extensors and flexors, and decreased in others, compared to control. The responses to platform translation were characterized by normal spatial and temporal patterns and latencies of EMG activity. Furthermore, all cats continued to use the force constraint strategy that is characteristic of the intact animal (Macpherson, 1988a). The only clear deficit in performance was a transient hypermetria, characterized by an over-response to the translation. Although the cats over-responded, they were still able to maintain their balance successfully. The moderate changes in quiet stance and in response to perturbation gradually returned to control values over 8-10 days following the lesion. These results suggest that vestibular information is not necessary for triggering appropriate postural responses evoked by support surface translations, nor for selecting the direction of response.

A system for the analysis of posture and stance in quadrupeds.

This paper describes a system for the quantitative analysis of posture and stance in the freely standing quadruped. The focal point of the system is a moving force platform operated by hydraulic servos under computer control. Cats are trained to stand on a support consisting of 4 force plates. Stance is perturbed by the controlled movement of the platform and the evoked postural responses are quantified in terms of the ground reaction forces, the activity of selected muscles, and the movements of the body segments. New developments that are described include: (1) the moving platform, (2) a miniature, triaxial force plate for detecting ground reaction forces under each paw, and (3) a new video camera capable of freezing rapid movements.

Postural orientation, equilibrium, and the spinal cord.

In summary, adequate control of postural orientation and equilibrium is a prerequisite for virtually all skilled motor acts, even those apparently simple tasks of standing and walking. In the cat, certain aspects of postural orientation appear to be organized at the spinal level. In contrast, postural equilibrium is not achieved by spinal circuits in isolation, but seems to require input from higher centers. The challenge is to identify those higher centers and the means by which they produce appropriate postural reactions for maintaining balance. If, indeed, postural equilibrium is a function of descending systems, then in the future, the amount of recovery of postural equilibrium after injury and/or treatment could provide a quantitative measure of the degree of sparing and/or re-establishment of functional connections between higher centers and the spinal cord.

Differentiation of seven Eimeria species by random amplified polymorphic DNA.

Eimeria species were differentiated by the polymerase chain reaction using random amplified polymorphic DNA. Seven arbitrary primers ranging in length from ten to 20 nucleotides were used with DNA of seven species of eimerian oocysts to generate unique DNA fingerprints. DNA fragments ranging from 200 to 2200 base pairs (bp) were synthesized in the different reactions. Species-specific DNA fragment mobility patterns were observed in most cases. In several assays, multiple DNA fragments were synthesized and, in the majority of assays conducted, the Eimeria species could be easily differentiated. Only six of the 49 assays performed failed to generate DNA fragments.

Specific amplification of Sarcocystis cruzi DNA using a randomly primed polymerase chain reaction assay.

The polymerase chain reaction (PCR) method to randomly amplify polymorphic DNA (RAPD) was used to differentiate between Sarcocystis cruzi DNA and bovine DNA. This assay was also exploited to identify a S. cruzi DNA fragment which may be useful as a probe. Five primers ranging in length from 16 to 20 nucleotides were analyzed for their ability to direct the amplification of either bovine or parasite DNA fragments. Two primers, TGA and TGD, preferentially amplified bovine DNA in a mixture of S. cruzi and bovine DNA. The primers TGB and TGF each directed the amplification of S. cruzi DNA instead of bovine DNA. Assays using TGF and S. cruzi DNA resulted in the production of a unique 0.8 kilobase (kb) DNA fragment. This fragment was not amplified from two other closely related coccidian species, Toxoplasma gondii and Sarcocystis campestris. When the 0.8 kb DNA fragment was purified and used as a DNA probe, it only hybridized with DNA from S. cruzi. The results of this study indicate that this DNA fragment may be developed into a useful DNA probe for S. cruzi, and that the RAPD-PCR method may be successfully exploited for the rapid development of DNA probes for parasites and other organisms.

Sensitive and specific polymerase chain reaction detection of Toxoplasma gondii for veterinary and medical diagnosis.

A polymerase chain reaction (PCR) method was developed for the detection of Toxoplasma gondii. A universal- and a T. gondii-specific primer was used to amplify a region of the small subunit ribosomal RNA gene. This approach allows for a theoretical detection limit of 0.01 zoite of T. gondii per sample assayed. Experiments showed that this PCR method could detect 0.1 pg of T. gondii DNA, which represents about one organism. Polymerase chain reaction tests using DNAs of cat, dog, swine, cattle, human, Sarcocystis cruzi, Eimeria ahsata, E. vermiformis, and Escherichia coli indicated no cross-reaction with nucleic acids of hosts, related coccidia, or bacteria. Data on the sensitivity and specificity suggest that this PCR assay could be extremely useful for the diagnosis of toxoplasmosis in human and veterinary medicine, as well as for food safety surveys.

Strategies that simplify the control of quadrupedal stance. I. Forces at the ground.

1. Postural reactions were studied in six cats subjected to small, linear translations of the supporting surface in each of 16 different directions in the horizontal plane. Directions were specified in a polar coordinate system, with posterior translations being 0 degrees and leftward translations, 90 degrees. The data consisted of the forces exerted by each paw of the cat against the ground, measured in three orthogonal directions, vertical (z-axis), longitudinal (y-axis), and lateral (x-axis). 2. The force traces were analyzed by measuring the area under the curve during the postural reaction and dividing by the time of integration to give an average change in force. These values were normalized and plotted against direction of translation in polar coordinates, to give force tuning curves. The longitudinal and lateral force components were combined to generate force vectors in the horizontal plane. 3. Every cat responded to the platform translations with the same, simple strategy in which each hindlimb actively produced a correction force vector in one of only two possible directions. Participation of the forelimbs in the horizontal plane correction was not obligatory. While the direction of each hindlimb force vector was invariant, the amplitude was modulated according to the direction of platform movement. The resultant force vector, that acts through the center of mass of the animal, was in a direction opposite to the platform movement and directly opposed the perturbation. By this strategy, the cat was able to correct for destabilizing movements of the supporting surface in any direction in the horizontal plane. 4. It is concluded that the generation of forces between the paws and the ground is a high-level parameter that is controlled by the nervous system in a task-dependent manner. By using the strategy of restricting these forces to a set of two direction-invariant vectors, the problem of maintaining stance in the face of horizontal plane disturbances is greatly simplified.

Strategies that simplify the control of quadrupedal stance. II. Electromyographic activity.

1. This study tested the hypothesis that muscle synergies underlie the invariance in the direction of corrective forces observed following stance perturbations in the horizontal plane. Electromyographic activity was recorded from selected forelimb and hindlimb muscles of cats subjected to horizontal translations of the supporting surface in 16 different directions. The responses of muscles were quantified for each perturbation, and tuning curves were constructed that related the amplitude of muscle response to the direction of platform movement. 2. Muscle tuning curves tended to group into one of two regions, corresponding to the two directions of force vectors. A few muscles showed clearly different recruitment patterns. The same direction of correction force vector was produced by different patterns of muscle activity, and the particular EMG pattern depended on the direction of platform movement. Therefore a simple muscle synergy organization could not account for the invariance in force vector generation. 3. It is concluded that there is a hierarchy of control in the maintenance of stance in which the vector of force exerted against the ground is a high level, task-dependent controlled variable and the selection of muscles to activate in order to produce the vector is controlled at a lower level. It is proposed that muscles are controlled using a modified synergy strategy. In this scheme, a synergy is not simply a fixed group of muscles, constrained to act as a unit. Rather, muscles are organized as a task-dependent synergy that is tuned or modified as needed by the addition or subtraction of other muscles.

Changes in a postural strategy with inter-paw distance.

1. The purpose of this study was to examine the effect of changing initial stance conditions on the postural response of the cat to horizontal plane translations of the support surface. Cats were trained to stand, unrestrained, on a moveable force platform. The platform was translated linearly in each of 16 directions in the horizontal plane, with a ramp-and-hold displacement. The animal's response was quantified in terms of the forces exerted at the ground. The trajectory of the center of mass (CoM) was computed from the forces. 2. Stance length was varied along the longitudinal (sagittal) axis by adjusting the distance between the forepaw and hindpaw force plates. Translation perturbations of the platform were recorded at stance distances varying from 66 to 110% of the preferred stance distance. 3. Changing stance distance had a significant effect on the amplitude and direction of the active forces exerted by the cat both during quiet stance and during the response to platform translation. At long stance distances, each limb exerted a force outward, along the diagonals during quiet stance. The response to translation was characterized by an invariance in the direction of force exerted against the ground, a strategy that was described previously. At short stance distances, quiet stance forces were more laterally directed. The force constraint strategy was usually not observed for the response to translation. Nevertheless, the cats were equally effective at all stance distances in restoring the position of the center of mass after translation of the support surface. 4. There was no discrete boundary between the presence and absence of the force constraint, suggesting that the strategy for exerting forces against the support surface is characterized by a continuum of response, from a bimodal, or anisotropic distribution of force vectors on the one extreme, to a uniform, or isotropic distribution on the other. Arguments are developed to suggest that the force constraint strategy may be useful in stabilizing the vertebral column during the response to platform translation, to allow linear translation of the CoM rather than bending of the trunk.

The force constraint strategy for stance is independent of prior experience.

The purpose of this study was to examine the effect of prior experience concerning direction of a postural perturbation on the balance response of cats to translations of their support surface. Previous work has shown that, when cats are translated in many directions in the horizontal plane, they respond by exerting active forces with each paw in only two directions, termed the force constraint strategy. This study examined whether the force constraint strategy could be modified based on predictability of the direction of translation and whether this strategy is used by the naive animal with no prior experience of platform translation. Four cats were trained to stand quietly on the force platform using positive reinforcement, and then were implanted with chronically indwelling electrodes for recording electromyographic (EMG) activity. The first experiment concerned the response of the naive cats to their first exposure to platform translation and consisted of translations presented randomly in four different directions in the horizontal plane. The second experiment consisted of two complete sets of 16 directions of translation (15 trials per direction), with the direction of translation randomized in one set and serially ordered in the other, to make the direction of translation unpredictable or predictable, respectively. Forces exerted by the cat, EMG activity, and platform position were recorded during the 1-s trials. The use of the force constraint strategy was independent of prior experience with direction of translation, as was the amplitude of the response.(ABSTRACT TRUNCATED AT 250 WORDS)

Bilateral labyrinthectomy in the cat: effects on the postural response to translation.

1. This study examined the role of vestibular afferent information on the postural responses of four cats, evoked by movements of the support surface during stance. Animals were exposed to linear translations of the supporting surface in eight evenly spaced directions in the horizontal plane, before and after bilateral labyrinthectomy. Postural responses were quantified in terms of the ground reaction forces under each paw and the evoked activity in selected muscles. 2. The cats were able to stand on the platform within 1-3 days after labyrinthectomy and were able to maintain balance during all perturbations of stance, even when they stood in total darkness, completely deprived of visual information. After lesion, postural responses were characterized by normal latency and normal spatial and temporal patterning of electromyographic (EMG) response. The pattern of force response showed the force constraint strategy that characterizes postural responses in the intact animal. 3. The only deficit in the postural response after lesion was a hypermetria, or active over-response that caused the animals to overbalance somewhat but did not impair their ability to remain upright. Analysis of the trajectory of the animal's center of mass during the trials indicated that the hypermetria was due to an abnormally large, active response on the part of the animal and could not be attributed to changes in the passive stiffness of the musculoskeletal system. The hypermetria was transient, and response amplitude returned to control levels after the rapid compensation phase of 10-15 days. 4. It is concluded that vestibular information is not essential for triggering the rapid, automatic postural response to translations of the support surface, nor is it necessary for the selection or shaping of the evoked response. Instead, somatosensory information appears to predominate in these postural adjustments. However, vestibular afferent input does influence the scaling of the postural response.

Head acceleration following linear translations in the freely-standing cat.

The aim of this study was to determine whether vestibular information related to head acceleration is available for triggering postural responses to perturbations of stance in the freely-standing cat. Linear accelerations of the head were recorded during postural responses evoked by linear translations of the support surface. A consistent initial peak of acceleration was observed at an average latency of 22 ms and magnitude of 0.03 g (g is acceleration due to gravity, 9.8 m/s/s). The acceleration peak preceded the first evoked EMG activity by an average of 24 ms. It was concluded that stimulation of the vestibular apparatus was both adequate and early enough for the vestibular system to have triggered the automatic postural response.

Functionally complex muscles of the cat hindlimb. III. Differential activation within biceps femoris during postural perturbations.

The biceps femoris (BF) muscle is divided into three neuromuscular compartments defined by the innervation patterns of the main nerve branches (English and Weeks 1987). The goals of this study were i) to determine how different regions of the biceps femoris muscle are activated in the intact cat during a broad range of limb movements evoked by perturbations of stance posture, and ii) to determine the relationship between the anatomical compartments of biceps femoris and the functional units as defined in this task. Cats were trained to stand on a moveable platform with each paw on a triaxial force plate. The animal's stance was perturbed by linear translation of the platform in each of sixteen different directions in the horizontal plane. EMG activity was recorded from eight sites across the width of the left biceps femoris muscle. During quiet stance only the anterior compartment was tonically active, presumably contributing to hip extensor torque in the maintenance of stance. During platform translation, evoked EMG activity was recorded from each electrode pair for a wide range of directions of perturbation; as direction changed progressively, the amplitude of evoked activity from any electrode pair increased to a maximum and then decreased. When the EMG amplitude was plotted in polar coordinates as a function of translation direction, the region of response formed a petal shaped area in the horizontal plane, termed the EMG tuning curve. The compartments of the BF muscle were not activated homogeneously. The tuning curve of the anterior BF compartment was similar to that of other hip extensors, and coincided with the region of postero-lateral force production by the hindlimb against the support. The tuning curve of the middle BF compartment was shifted in a counterclockwise direction from that of the anterior compartment, but overlapped extensively with it; the middle BF tuning curve was similar to that of anterior gracilis. The tuning curve of the posterior biceps compartment was rotated further counterclockwise and overlapped very little with that of the middle BF compartment. The posterior BF was activated in a pattern similar to that of other knee flexors. The functional units of BF activation were not identical with the neuromuscular compartments defined by the main nerve branches. As direction of the perturbation changed, the region of BF that was activated moved progressively across the muscle. This progression of the active region was continuous across BFa and BFm, whereas there was a jump, or discontinuity at the border between BFm and BFp.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of head position on postural orientation and equilibrium.

This study examined (1) how changes in head position affect postural orientation variables during stance and (2) whether changes in head position affect the rapid postural response to linear translation of the support surface in the horizontal plane. Cats were trained to stand quietly on a moveable platform and to maintain five different head positions: center, left, right, up, and down. For each head position, stance was perturbed by translating the support surface linearly in 16 different directions in the horizontal plane. Postural equilibrium responses were quantified in terms of the ground reaction forces, kinematics, dynamics (net joint torques), body center of mass, and electromyographic (EMG) responses of selected limb and trunk muscles. A change in head position involved rotation of not only the neck but also the scapulae and anterior trunk. Tonic EMG levels were modulated in several forelimb and scapular muscles but not hindlimb muscles. Finally, large changes in head orientation in both horizontal and vertical planes did not hamper the ability of cats to maintain postural equilibrium during linear translation of the support surface. The trajectory of the body's center of mass was the same, regardless of head position. The main change was observed in joint torques at the forelimbs evoked by the perturbation. Evoked EMG responses of forelimb and scapular muscles were modulated in terms of magnitude but not spatial tuning. Hindlimb responses were unchanged. Thus, the spatial and temporal pattern of the automatic postural response was unchanged and only amplitudes of evoked activity were modulated by head position.