Ontogenetic adaptation to bipedalism: age changes in femoral to humeral length and strength proportions in humans, with a comparison to baboons

The increase in lower/upper limb bone length and strength proportions in adult humans compared to most other anthropoid primates is commonly viewed as an adaptation to bipedalism. The ontogenetic development of femoral to humeral proportions is examined here using a longitudinal sample of 20 individuals measured radiographically at semiannual or annual intervals from 6 months of age to late adolescence (a subset of the Denver Growth Study sample). Anthropometric data (body weights, muscle breadths) were also available at each examination age. Results show that while femoral/humeral length proportions close to those of adults are already present in human infants, characteristically human femoral/humeral diaphyseal strength proportions only develop after the adoption of bipedalism at about 1 year of age. A rapid increase in femoral/humeral strength occurs between 1 and 3 years, followed by a slow increase until mid-late adolescence, when adult proportions are reached. When age changes in material properties are factored in, femoral strength shows an almost constant relationship to body size (body mass.bone length) after 5 years of age, while humeral strength shows a progressive decline relative to body size. Femoral/humeral length proportions increase slightly throughout growth, with no apparent change in growth trajectory at the initiation of walking, and with a small decline in late adolescence due to later growth in length of the humerus. A sex difference in femoral/humeral strength proportions (females greater) but not length proportions, develops early in childhood. Thus, growth trajectories in length and strength proportions are largely independent, with strength proportions more responsive to actual changes in mechanical loading. A cross-sectional ontogenetic sample of baboons (n=30) illustrates contrasting patterns of growth, with much smaller age changes in proportions, particularly strength proportions, although there is some indication of an adaptation to altered limb loadings early in baboon development.     

Characterization of TsaR,an oxygen-sensitive LysR-type regulator for the degradation of p-toluenesulfonate in Comamonas testosteroni T-2

TsaR is the putative LysR-type regulator of the tsa operon (tsaMBCD) which encodes the first steps in the degradation of p-toluenesulfonate (TSA) in Comamonas testosteroni T-2. Transposon mutagenesis was used to knock out tsaR. The resulting mutant lacked the ability to grow with TSA and p-toluenecarboxylate (TCA). Reintroduction of tsaR in trans on an expression vector reconstituted growth with TSA and TCA. The tsaR gene was cloned into Escherichia coli with a C-terminal His tag and overexpressed as TsaR(His). TsaR(His) was subject to reversible inactivation by oxygen, which markedly influenced the experimental approaches used. Gel filtration showed TsaR(His) to be a monomer in solution. Overexpressed TsaR(His) bound specifically to three regions within the promoter between the divergently transcribed tsaR and tsaMBCD. The dissociation constant (K(D)) for the whole promoter region was about 0.9 micro M, and the interaction was a function of the concentration of the ligand TSA. A regulatory model for this LysR-type regulator is proposed on the basis of these data.     

Changes in contractile properties of skeletal muscle during developmentally programmed atrophy and death

Skeletal muscle atrophyand death are protracted processes that accompany aging andpathological insults in mammals. The intersegmental muscles (ISMs) fromthe tobacco hawkmoth Manduca sexta are composed of giantfibers that undergo distinct hormonally-regulated programs of atrophyand death at the end of metamorphosis. Atrophy occurs during the 3 dayspreceding adult emergence and results in a 40% reduction of mass,whereas death takes place during the subsequent 30 h and resultsin the complete loss of the fibers. There are no significant changes intetanic force or calcium sensitivity in skinned fiber preparationsduring atrophy. However, the size of caffeine-induced contractions fellby about 50%. With the onset of the death phase, dramatic reductionsoccur in ISM: tetanic force, twitch amplitude, resting potential,caffeine-induced contractions, calcium sensitivity, and Hillcoefficients. Several lines of evidence suggest that ISM atrophy iscaused by an increase in protein turnover without significantmodification of fiber organization. In contrast, ISM death isaccompanied by disorganization of the contractile apparatus andconcomitant loss of contractile function.

     

Postcranial robusticity in Homo. II: Humeral bilateral asymmetry and bone plasticity

The analysis of humeral asymmetry in Recent human skeletal samples and an extant tennis-player sample documents minimal asymmetry in bone length, little asymmetry in distal humeral articular breadth, but pronounced and variable asymmetry in mid- and distal diaphyseal crosssectional geometric parameters. More specifically, skeletal samples of normal modern Euroamericans, prehistoric and early historic Amerindians, and prehistoric Japanese show moderate (ca. 5–14%) median asymmetry in diaphyseal cross-sectional areas and polar second moments of area, whereas the tennis-player sample, with pronounced unilateral physical activity, exhibits median asymmetries of 28–57% in the same parameters. A sample of Neandertals with nonpathological upper limbs exhibits similarly low articular asymmetry but pronounced diaphyseal asymmetries, averaging 24–57%. In addition, three Neandertals with actual or possible post-traumatic upper limb alterations have the same low articular asymmetry but extremely high diaphyseal asymmetries, averaging 112–215%. These data support those from experimental work on animals, exercise programs of humans, and human clinical contexts in establishing the high degree of diaphyseal plasticity possible for humans, past and present, under changing biomechanical loading conditions. This lends support to activity-related functional interpretations of changing human diaphyseal morphology and robusticity during the Pleistocene. © 1994 Wiley-Liss, Inc.     

The kinetics of local anesthetic blockade of end-plate channels

The effect of the local anesthetic QX222 on the kinetics of miniature end-plate currents (MEPC)and acetylcholine-induced end-plate current fluctuations was studied in voltage-clamped frog cutaneous pectoris neuromuscular junctions. The rate constants for a kinetic scheme of local anesthetic blockage of end-plate channels were calculated from the MEPC decay parameters. At 18 degrees C the blocking rate constant was 1.1 +/- 0.3 x 10(7) exp (-0.009 +/- 0.003 x V)s -1M-1, and the unblocking rate constant was 5.7 +/- 0.6 exp (0.011 +/- 0.002 x V)s -1. The dissociation constant was close to 10 microM at -80 mV. End-plate fluctuations indicated that the local anesthetic QX222 lowered the effective single-channel conductance, suggesting a finite blocked state conductance that was calculated to be 1.6 pS. The apparent differences between QX222 interaction with end-plate and extrajunctional channels are discussed.     

Isolation and identification of a peptide from rat brain which inhibits [3H]TCP binding.

1. A stereospecific radioreceptor binding assay for the phencyclidine analogue [3H]TCP was utilized to screen for inhibitors of binding in extracts of rat brain. 2. Extracts were prepared from rat cortex and hippocampus by methods employing aqueous acid or acidified methanol. Samples were fractionated by reversed phase-HPLC (RP-HPLC) and tested for activity in the radioreceptor assay. Three zones of activity were detected. The most active fraction was further purified by high performance-size exclusion chromatography. 3. Size exclusion chromatography revealed two zones of activity, corresponding to mol. wts of 4000-8000 Da and 1000-2000 Da. Final purification of the lower molecular weight material was achieved by RP-HPLC. 4. Two well-separated peaks were shown to be homogeneous. Their amino acid sequences were determined by automated Edman degradation and data base searching identified these two peaks as the undecapeptide Substance P and its oxidized counterpart (Substance P sulfoxide). 5. Comparative HPLC of synthetic Substance P, or its sulfoxide, as well as spectral analysis confirmed the identity of the isolated peptides. 6. Synthetic Substance P inhibits specific [3H]TCP binding in the radioreceptor assay.     

Crystallization and preliminary X-ray analysis of Escherichia coli methionyl–tRNA formyltransferase

Methionyl–tRNA formyltransferase from Escherichia coli, a monomer of 34kDa, was overexpressed from its cloned gene fmt (Guillon, J.M., Mechulam, Y., Schmitter, J.M., Blanquet, S., and Fayat, G., J. Bacteriol. 174:4294–4301, 1992) and crystallized using ammonium sulphate as precipitant. The crystals are trigonal and have unit cell parameters a = b = 151.0Å, c = 81.8Å. They belong to space group P3₂21 and diffract to 2.0Å resolution. The structure is being solved by multiple isomorphous replacement. © 1996 Wiley-Liss, Inc.     

Developmental changes of cardiac function and mass assessed with MRI in neonatal, juvenile, and adult mice

Cardiovascular transgenic mouse models with an early phenotype or even premature death require noninvasive imaging methods that allow for accurate visualization of cardiac morphology and function. Thus the purpose of our study was to assess the feasibility of magnetic resonance imaging (MRI) to characterize cardiac function and mass in newborn, juvenile, and adult mice. Forty-five C57bl/6 mice from seven age groups (3 days to 4 mo after birth) were studied by MRI under isoflurane anesthesia. Electrocardiogram-gated cine MRI was performed with an in-plane resolution of (78-117 microm)(2). Temporal resolution per cine frame was 8.6 ms. MRI revealed cardiac anatomy in mice from all age groups with high temporal and spatial resolution. There was close correlation between MRI- and autopsy-determined left ventricular (LV) mass (r = 0.95, SE of estimate = 9.5 mg). The increase of LV mass (range 9.6-101.3 mg), cardiac output (range 1.1-14.3 ml/min), and stroke volume (range 3. 2-40.2 microl) with age could be quantified by MRI measurements. Ejection fraction and cardiac index did not change with aging. However, LV mass index decreased with increasing age (P < 0.01). High-resolution MRI allows for accurate in vivo assessment of cardiac function in neonatal, juvenile, and adult mice. This method should be useful when applied in transgenic mouse models.