A test of Przibram's Rule

Przibram's Rule states that the ratio of the mean weights in successive instars of hemimetabolous insects is 2.09. Faber (1994) described a two-stage approach to testing Przibram's Rule when the instars of the measured individuals are unknown. In the first stage, individuals are assigned to one of the instars on the basis of their weights. In the second stage, a test of the null hypothesis that the means of logarithmic weight in the two groups differ by the logarithm of 2.09 is performed. This approach suffers from two problems. First, errors in assigning individuals to instars will exaggerate the difference between instars. Secondly, the validity of the test in the second stage is based on the implicit assumption that the variance of logarithmic weight in the two groups is equal. This note describes a test of Przibram's Rule that avoids these problems.     

Targeting transcription of MCL-1 sensitizes HER2-amplified breast cancers to HER2 inhibitors

Human epidermal growth factor receptor 2 gene (HER2) is focally amplified in approximately 20% of breast cancers. HER2 inhibitors alone are not effective, and sensitizing agents will be necessary to move away from a reliance on heavily toxic chemotherapeutics. We recently demonstrated that the efficacy of HER2 inhibitors is mitigated by uniformly low levels of the myeloid cell leukemia 1 (MCL-1) endogenous inhibitor, NOXA. Emerging clinical data have demonstrated that clinically advanced cyclin-dependent kinase (CDK) inhibitors are effective MCL-1 inhibitors in patients, and, importantly, well tolerated. We, therefore, tested whether the CDK inhibitor, dinaciclib, could block MCL-1 in preclinical HER2-amplified breast cancer models and therefore sensitize these cancers to dual HER2/EGFR inhibitors neratinib and lapatinib, as well as to the novel selective HER2 inhibitor tucatinib. Indeed, we found dinaciclib suppresses MCL-1 RNA and is highly effective at sensitizing HER2 inhibitors both in vitro and in vivo. This combination was tolerable in vivo. Mechanistically, liberating the effector BCL-2 protein, BAK, from MCL-1 results in robust apoptosis. Thus, clinically advanced CDK inhibitors may effectively combine with HER2 inhibitors and present a chemotherapy-free therapeutic strategy in HER2-amplified breast cancer, which can be tested immediately in the clinic.Subject terms: Breast cancer, Target identification     

Toward improved endoscopic surveillance with multidiameter single fiber reflectance spectroscopy in patients with Barrett's esophagus

Patients with Barrett's esophagus are at an increased risk to develop esophageal cancer and, therefore, undergo regular endoscopic surveillance. Early detection of neoplasia enables endoscopic treatment, which improves outcomes. However, early Barrett's neoplasia is easily missed during endoscopic surveillance. This study investigates multidiameter single fiber reflectance spectroscopy (MDSFR) to improve Barrett's surveillance. Based on the concept of field cancerization, it may be possible to identify the presence of a neoplastic lesion from measurements elsewhere in the esophagus or even the oral cavity. In this study, MDSFR measurements are performed on non-dysplastic Barrett's mucosa, squamous mucosa, oral mucosa, and the neoplastic lesion (if present). Based on logistic regression analysis on the scattering parameters measured by MDSFR, a classifier is developed that can predict the presence of neoplasia elsewhere in the Barrett's segment from measurements on the non-dysplastic Barrett's mucosa (sensitivity 91%, specificity 71%, AUC = 0.77). Classifiers obtained from logistic regression analysis for the squamous and oral mucosa do not result in an AUC significantly different from 0.5.     

Chemo- and stereo-selective biocatalytic reduction of α,β-unsaturated ketones employing a chemo-tolerant ADH from Rhodococcus ruber DSM 44541

Biocatalytic reduction of the keto-moiety of α,β-unsaturated ketones (enones) was achieved with absolute chemo- and stereo-selectivity employing whole lyophilized cells of Rhodococcus ruber DSM 44541 to furnish the corresponding allylic alcohols in e.e. up to >99%. It was shown that a stereocenter in γ-position of the ketone moiety to be reduced is too distant from the reaction center to induce any significant diastereoselectivity, thus no kinetic resolution of an racemic ketone occurred.     

Stabilization of Candida lipase against acetaldehyde by adsorption onto celite

Summary Immobilization of Candida rugosa lipase (Amano AY-30) by adsorption onto Celite 545 led to a markedly improved performance of the enzyme: Firstly, the enzyme was almost completely resistant to deactivation by acetaldehyde, which is liberated as unavoidable by-product in acyl-transfer reactions with vinyl esters, and secondly, the enantioselectivity was enhanced up to three-fold.     

Morphogenesis of mesenchyme from regeneration blastemas in the absence of digit formation in ambystoma mexicanum

Summary 1. Undifferentiated fore limb blastemas were denuded of their epidermis and grafted to the flank musculature; each transplant consisted of four such blastemas. Outgrowth of the mesenchyme and subsequent digit formation were prevented by covering the transplants with whole flank skin with its dermis intact. 2. Notwithstanding the absence of digits, 26 out of the 36 differentiated transplants formed one or two oblong, stout cartilages resembling proximal skeletal elements of the limb. Considering that four blastemas had been grafted in random orientation, this indicates considerable intrinsic morphogenetic capacities of the blastemal mesenchyme in the absence of organizing influences of the epidermis. 3. Thus, although permanent contact with wound epidermis has previously been shown to be necessary for blastemal mesenchyme to form distal limb structures, such contact is not required for the formation of proximal skeletal elements. The implications of this finding for regional organization in the regenerating limb are discussed.On leave from Department of Zoology, Faculty of Science, Alexandria University, Alexandria. Egypt.     

Qualitative and quantitative analysis of some synthetic, chemically acting laxatives in urine by gas chromatography—mass spectrometry

A method for the qualitative and quantitative simultaneous analysis of dioxyanthraquinone, desacetyl-Bisacodyl, phenolphthalein and Oxyphenisatin in human urine using gas chromatography—mass spectrometry (GC—MS) has been developed. The compounds were extracted from urine at pH 7.5 with diethyl ether using Extrelut extraction columns, followed by evaporation and trimethylsilylation.The method used electron beam ionization GC—MS employing a computer-controlled multiple-ion detector (mass fragmentography). The recovery from urine for the various compounds was between 80% and 100%. The detection limit for these compounds was in the range 0.01–0.05 μg/ml of urine.The method proved to be suitable for measuring urine concentrations for at least four days after administration of a single oral low therapeutic dose of the laxatives to sixteen healthy volunteers.