Semi‐supervised determination of pseudocryptic morphotypes using observer‐free characterizations of anatomical alignment and shape

Accurate, quantitative characterization of complex shapes is recognized as a key methodological challenge in biology. Recent development of automated three‐dimensional geometric morphometric protocols (auto3dgm) provides a promising set of tools to help address this challenge. While auto3dgm has been shown to be useful in characterizing variation across clades of morphologically very distinct mammals, it has not been adequately tested in more problematic cases where pseudolandmark placement error potentially confounds interpretation of true shape variation. Here, we tested the sensitivity of auto3dgm to the degree of variation and various parameterization settings using a simulation and three microCT datasets that characterize mammal tooth crown morphology as biological examples. The microCT datasets vary in degree of apparent morphological differentiation, with two that include grossly similar morphospecies and one that includes two laboratory strains of a single species. Resulting alignments are highly sensitive to the number of pseudolandmarks used to quantify shapes. The degree to which the surfaces were downsampled and the apparent degree of morphological differentiation across the dataset also influenced alignment repeatability. We show that previous critiques of auto3dgm were based on poorly parameterized alignments and suggest that sample‐specific sensitivity analyses should be added to any research protocol including auto3dgm. Auto3dgm is a useful tool for studying samples when pseudolandmark placement error is small relative to the true differences between specimens. This method therefore represents a promising avenue forward in morphometric studies at a wide range of scales, from samples that differ by a single genetic locus to samples that represent multiple phylogenetically diverse clades.     

Timing of neuromuscular activation of the quadriceps and hamstrings prior to landing in high school male athletes, female athletes, and female non-athletes.

There is a discrepancy between males and females in regards to lower extremity injury rates, particularly at the knee [Agel, J., Arendt, E.A., Bershadsky, B., 2005. Anterior cruciate ligament injury in National Collegiate Athletic Association basketball and soccer: a 13-year review. American Journal of Sports Medicine 33, (4) 524-530]. Gender differences in neuromuscular recruitment characteristics of the muscles that stabilize the knee are often implicated as a factor in this discrepancy. There is considerable research in the area of gender differences in regards to neuromuscular characteristics of the lower extremity in response to perturbation; however, most studies have been performed on the adult population only. Additionally, there is no consensus as to the gender differences that have been demonstrated. The purpose of this study was to compare muscular preactivation of selected lower extremity muscles (vastus medialis, rectus femoris, and medial/lateral hamstrings) in adolescent female basketball athletes, male basketball athletes, and female non-athletes in response to a drop landing. Subjects in the female non-athlete group recruited rectus femoris significantly slower than both the female athlete and male athlete groups (619.9=588.5>200.1ms prior to ground contact). The female non-athlete group also demonstrated a significantly slower vastus medialis compared to the female athlete group (127.1 vs 408.1ms), but not significantly slower than the male athlete group (127.1 vs 275.7ms). There were no differences between female athletes and male athletes for time to initial contraction of any muscle groups. No differences were found among the groups for medial or lateral hamstring activation. This study demonstrates that physical conditioning due to basketball participation appears to affect neuromuscular recruitment in adolescents and reveals a necessity to find alternate methods of training the hamstrings for improved neuromuscular capabilities to prevent injury.     

A quantitative analysis of kinase inhibitor selectivity

Kinase inhibitors are a new class of therapeutics with a propensity to inhibit multiple targets. The biological consequences of multi-kinase activity are poorly defined, and an important step toward understanding the relationship between selectivity, efficacy and safety is the exploration of how inhibitors interact with the human kinome. We present interaction maps for 38 kinase inhibitors across a panel of 317 kinases representing >50% of the predicted human protein kinome. The data constitute the most comprehensive study of kinase inhibitor selectivity to date and reveal a wide diversity of interaction patterns. To enable a global analysis of the results, we introduce the concept of a selectivity score as a general tool to quantify and differentiate the observed interaction patterns. We further investigate the impact of panel size and find that small assay panels do not provide a robust measure of selectivity.     

Caring during crisis: animal welfare during pandemics and natural disasters

From April 29 to May 1, 2007, the University of Guelph hosted a symposium, Caring During Crisis: Animal Welfare During Pandemics and Natural Disasters, with the objectives (a) of raising awareness about how nonhuman animals and the people who care for them are affected during emergencies and (b) of sharing knowledge about how animal welfare may be addressed during these situations. The symposium attracted 150 participants, representing 71 organizations from across Canada, the United States, the United Kingdom, Australia, Chile, and the Cayman Islands. The audience also brought a range of perspectives to the issues—from individuals representing animal protection and commodity organizations to municipal government officials responsible for community safety and correctional services; many of these individuals had little or no animal experience. To take advantage of this diverse audience and range of interests, the symposium was structured with formal presentations by internationally recognized experts, followed by panel discussions at the end of each session to facilitate contributions by the audience. At the conclusion of the 3 days, it was clear that our emotional, economic, and ecological relationships with animals require thoughtful integration of animal care within formal policy and planning for emergency response.     

Tandem immunoprecipitation of phosphotyrosine-mass spectrometry (TIPY-MS) indicates C19ORF19 becomes tyrosine-phosphorylated and associated with activated epidermal growth factor receptor

To identify phosphotyrosine (pY) sites in the epidermal growth factor receptor (EGFR) network, a tandem immunoprecipitation-mass spectrometry method (TIPY-MS) was applied wherein protease-digested EGFR immune complexes were extracted with anti-pY after Rush et al. ( Nat. Biotech. 2005, 23, 94 ) and analyzed by LC-MS/MS. New pY sites in the pathway were found, including SOS1 Y1065, SOS2 Y1275, CBL-B Y889, and in the EGFR regulatory protein Mig-6 Y458. The novel human C19orf19 gene product was found EGFR-associated and phosphorylated at 5 tyrosines in response to EGFR activation and, therefore, represents a new component of the EGFR signaling network.     

C-terminal phosphorylation of murine testis-specific histone H1t in elongating spermatids

Previous studies gave differing results as to whether the testis-specific histone H1t was phosphorylated during rodent spermatogenesis. We show here that histones extracted from germ cell populations enriched with spermatids at different stages of development in rat testes reveal an electrophoretic shift in the position of H1t to slower mobilities in elongating spermatids as compared to that from preceding stages. Alkaline phosphatase treatment and radioactive labeling with (32)P demonstrated that the electrophoretic shift is due to phosphorylation. Mass spectrometric analysis of histone H1t purified from sexually mature mice and rat testes confirmed the occurrence of singly, doubly, and triply phosphorylated species, with phosphorylation sites predominantly found at the C-terminal end of the molecule. Furthermore, using collision-activated dissociation (CAD) and electron transfer dissociation (ETD), we have been able to identify the major phosphorylation sites. These include a new, previously unidentified putative H1t-specific cdc2 phosphorylation site in linker histones. The presence of phosphorylation at the C-terminal end of H1t and the timing of its appearance suggest that this post-translational modification is involved in the reduction of H1t binding strength to DNA. It is proposed that this could participate in the opening of the chromatin fiber in preparation for histone displacement by transition proteins in the next phase of spermiogenesis.