Synthesis and biological effect of the C-terminal pentapeptide amide of avian pancreatic hormone III (APP).

Model building studies and analogies drawn from peptides of similar biological activity have indicated that the C-terminus of avian pancreatic hormone III may possess significant biological information. To test this hypothesis, the C-terminal pentapeptide amide sequence has been synthesized by the Merrifield method. The synthesis, purification and characterization of this compound are reported here in detail. In vivo studies indicate that this synthetic segment possesses none of the secretogogic activity of the parent hormone; rather, it reduces "gastric" secretion levels even in the presence of the intact hormone.     

Paleoepidemiological patterns of interpersonal aggression in a prehistoric central California population from CA‐ALA‐329

Interpersonal aggression is assessed paleoepidemiologically in a large skeletal population from the CA‐ALA‐329 site located on the southeastern side of San Francisco Bay, California. This comprehensive analysis included all currently recognized skeletal criteria, including craniofacial fracture, projectile injury, forearm fracture, and perimortem bone modification. Craniofacial injury is moderately common, showing an adult prevalence of 9.0% with facial lesions accounting for >50% of involvement. Clinical studies suggest that such separate evaluation of facial involvement provides a useful perspective for understanding patterns of interpersonal aggression. In this group male facial involvement is significantly greater than in females, paralleling the pattern found widely in contemporary populations as well as in African apes. When compared to other North American skeletal samples the prevalence of adult cranial vault injury (3.3%) and especially projectile injury (4.4%) are quite high. However, well documented populations from southern California show markedly higher prevalence for both types of skeletal markers of aggression. Forearm fracture is also assessed using a rigorous radiographic methodology and results suggest that these injuries are not reliable indicators of interpersonal aggression. Lastly, perimortem bone modification was not observed in this population, although it has been recorded from other (older) sites nearby. This study provides an evaluation of multiple skeletal markers of interpersonal aggression in the largest sample from a single site yet reported in North America and, joined with consideration of cultural context, helps further illuminate both geographic and temporal patterns of interpersonal aggression in California. Am J Phys Anthropol, 2009. © 2009 Wiley‐Liss, Inc.     

In vitro articular cartilage growth with sequential application of IGF-1 and TGF-β1 enhances volumetric growth and maintains compressive properties

In vitro cultures with insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1) have previously been shown to differentially modulate the growth of immature bovine articular cartilage. IGF-1 stimulates expansive growth yet decreases compressive moduli and increases compressive Poisson's ratios, whereas TGF-β1 maintains tissue size, increases compressive moduli, and decreases compressive Poisson's ratios. The current study's hypothesis was that sequential application of IGF-1 and TGF-β1 during in vitro culture produces geometric and compressive mechanical properties that lie between extreme values produced when using either growth factor alone. Immature bovine articular cartilage specimens were harvested and either untreated (D0, i.e., day zero) or cultured in vitro for either 6 days with IGF-1 (D6 IGF), 12 days with IGF-1 (D12 IGF), or 6 days with IGF-1 followed by 6 days with TGF-β1 (D12 SEQ, i.e., sequential). Following treatment, all specimens were tested for geometric, biochemical, and compressive mechanical properties. Relative to D0, D12 SEQ treatment enhanced volumetric growth, but to a lower value than that for D12 IGF. Furthermore, D12 SEQ treatment maintained compressive moduli and Poisson's ratios at values higher and lower, respectively, than those for D12 IGF. Considering the previously described effects of 12 days of treatment with TGF-β1 alone, D12 SEQ induced both growth and mechanical property changes between those produced with either IGF-1 or TGF-β1 alone. The results suggest that it may be possible to vary the durations of select growth factors, including IGF-1 and TGF-β1, to more precisely modulate the geometric, biochemical, and mechanical properties of immature cartilage graft tissue in clinical repair strategies.     

Localization of the ethylene receptor ETR1 to the endoplasmic reticulum of Arabidopsis

The ethylene receptor ETR1 of Arabidopsis contains transmembrane domains responsible for ethylene binding and membrane localization. Sequence analysis does not provide information as to which membrane system of the plant cell ETR1 is localized. Examination by aqueous two-phase partitioning, sucrose density-gradient centrifugation, and immunoelectron microscopy indicates that ETR1 is predominantly localized to the endoplasmic reticulum. Localization of ETR1 showed no change following a cycloheximide chase. Ethylene binding by ETR1 did not affect localization to the endoplasmic reticulum, based upon analysis of plants treated with the ethylene precursor 1-aminocyclopropane- 1-carboxylic acid and by examination of a mutant receptor that does not bind ethylene. Determinants within the amino-terminal half of ETR1 are sufficient for targeting to and retention at the endoplasmic reticulum. These data support a central role of the plant endoplasmic reticulum in hormone perception and signal transduction.     

The R403Q myosin mutation implicated in familial hypertrophic cardiomyopathy causes disorder at the actomyosin interface

Background

Mutations in virtually all of the proteins comprising the cardiac muscle sarcomere have been implicated in causing Familial Hypertrophic Cardiomyopathy (FHC). Mutations in the β-myosin heavy chain (MHC) remain among the most common causes of FHC, with the widely studied R403Q mutation resulting in an especially severe clinical prognosis. In vitro functional studies of cardiac myosin containing the R403Q mutation have revealed significant changes in enzymatic and mechanical properties compared to wild-type myosin. It has been proposed that these molecular changes must trigger events that ultimately lead to the clinical phenotype.

Principal Findings

Here we examine the structural consequences of the R403Q mutation in a recombinant smooth muscle myosin subfragment (S1), whose kinetic features have much in common with slow β-MHC. We obtained three-dimensional reconstructions of wild-type and R403Q smooth muscle S1 bound to actin filaments in the presence (ADP) and absence (apo) of nucleotide by electron cryomicroscopy and image analysis. We observed that the mutant S1 was attached to actin at highly variable angles compared to wild-type reconstructions, suggesting a severe disruption of the actin-myosin interaction at the interface.

Significance

These results provide structural evidence that disarray at the molecular level may be linked to the histopathological myocyte disarray characteristic of the diseased state.     

Use of equine chorionic gonadotrophin in female mink

This study was comprised of three trials to determine the effects of equine chrionic gonadotrophin (eCG) on induction of sexual receptivity in female mink that had failed to mate by late in the breeding season. In the first trial one ovary was removed from unmated mink, which were then injected with 100 IU eCG. This treatment induced ovarian activity, including ovulation in the remaining ovary. In the second experiment, mink that had not been observed to mate were treated with 100 IU eCG or saline, resulting in mating of 10 11 of the eCG-treated animals, compared to 5 11 controls. Litter sizes were larger in mink in the control group, suggesting that eCG interfered with some phase of the reproductive process. In the third trial, 226 mink that had failed to mate until late in the breeding season were treated with 100 IU eCG. Of the 191 that subsequently mated, 99 produced litters, but litter sizes were reduced slightly from those observed in the remainder of the herd that bred without hormone treatment prior to March 20. Neonatal kit loss per female whelping was greater in mink treated with eCG. It is concluded that eCG treatment will induce mating in mink that refuse to mate, but this treatment results in reduced whelping success and greater neonatal kit loss. Its utility may be restricted to salvage situations where large numbers of mink fail to mate.