Number and Distribution of Superficial Neuromasts in Twelve Common European Cypriniform Fishes and Their Relationship to Habitat Occurrence

This paper gives the first detailed data on the number and body part related distribution of superficial neuromasts in twelve common European Cypriniform species and examines whether such anatomical variables can be related to rough scale habitat occurrence. The fishes (Barbatula barbatula, Barbus barbus, Chondrostoma nasus, Cobitis taenia, Leuciscus cephalus, Leuciscus leuciscus, Phoxinus phoxinus, Rutilus rutilus, Rhodeus sericeus, Scardinius erythrophthalmus, Tinca tinca, Vimba vimba) were classified in two generalized ‘ecological guilds’, 1) rheophilic and 2) limnophilic or indifferent, based on literature data. The total number of superficial neuromasts was consistent within each species, but differed considerably between species. Lowest numbers of superficial neuromasts were found in Barbatula barbatula (21 ± 4.9 superficial neuromasts per cm body length) (mean ± SD), highest numbers in Vimba vimba (233 ± 36.1). Both species can be classified as rheophilic. Over all no relationship was found between the total number of superficial neuromasts and large scale habitat occurrence. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Cdk1 Activity Is Required for Mitotic Activation of Aurora A during G2/M Transition of Human Cells

In mammalian cells entry into and progression through mitosis are regulated by multiple mitotic kinases. How mitotic kinases interact with each other and coordinately regulate mitosis remains to be fully understood. Here we employed a chemical biology approach using selective small molecule kinase inhibitors to dissect the relationship between Cdk1 and Aurora A kinases during G₂/M transition. We find that activation of Aurora A first occurs at centrosomes at late G₂ and is required for centrosome separation independently of Cdk1 activity. Upon entry into mitosis, Aurora A then becomes fully activated downstream of Cdk1 activation. Inactivation of Aurora A or Plk1 individually during a synchronized cell cycle shows no significant effect on Cdk1 activation and entry into mitosis. However, simultaneous inactivation of both Aurora A and Plk1 markedly delays Cdk1 activation and entry into mitosis, suggesting that Aurora A and Plk1 have redundant functions in the feedback activation of Cdk1. Together, our data suggest that Cdk1, Aurora A, and Plk1 mitotic kinases participate in a feedback activation loop and that activation of Cdk1 initiates the feedback loop activity, leading to rapid and timely entry into mitosis in human cells. In addition, live cell imaging reveals that the nuclear cycle of cells becomes uncoupled from cytokinesis upon inactivation of both Aurora A and Aurora B kinases and continues to oscillate in a Cdk1-dependent manner in the absence of cytokinesis, resulting in multinucleated, polyploidy cells.     

Imatinib has a fatal impact on morphology, pairing stability and survival of adult Schistosoma mansoni in vitro

Schistosomes cause bilharzia (schistosomiasis), one of the most prevalent parasitic diseases for human and animals worldwide. Praziquantel (PZQ) is the only widely used drug for treatment and control of this parasitemia. Since a vaccine is not yet available, and in light of emerging resistance against PZQ, the search for alternatives has high priority. Here we present that Imatinib, a compound used in human cancer therapy (Gleevec; STI-571), significantly affected schistosome morphology and physiology in vitro. Besides its negative effect on gonad development and pairing stability, Imatinib led to pathological alterations of the gastrodermis, which finally caused the death of the parasite.     

Association of Early Repolarization Pattern on ECG with Risk of Cardiac and All-Cause Mortality: A Population-Based Prospective Cohort Study (MONICA/KORA)

Background

Early repolarization pattern (ERP) on electrocardiogram was associated with idiopathic ventricular fibrillation and sudden cardiac arrest in a case-control study and with cardiovascular mortality in a Finnish community-based sample. We sought to determine ERP prevalence and its association with cardiac and all-cause mortality in a large, prospective, population-based case-cohort study (Monitoring of Cardiovascular Diseases and Conditions [MONICA]/KORA [Cooperative Health Research in the Region of Augsburg]) comprised of individuals of Central-European descent.

Methods and Findings

Electrocardiograms of 1,945 participants aged 35–74 y, representing a source population of 6,213 individuals, were analyzed applying a case-cohort design. Mean follow-up was 18.9 y. Cause of death was ascertained by the 9th revision of the International Classification of Disease (ICD-9) codes as documented in death certificates. ERP-attributable effects on mortality were determined by a weighted Cox proportional hazard model adjusted for covariables. Prevalence of ERP was 13.1% in our study. ERP was associated with cardiac and all-cause mortality, most pronounced in those of younger age and male sex; a clear ERP-age interaction was detected (p = 0.005). Age-stratified analyses showed hazard ratios (HRs) for cardiac mortality of 1.96 (95% confidence interval [CI] 1.05–3.68, p = 0.035) for both sexes and 2.65 (95% CI 1.21–5.83, p = 0.015) for men between 35–54 y. An inferior localization of ERP further increased ERP-attributable cardiac mortality to HRs of 3.15 (95% CI 1.58–6.28, p = 0.001) for both sexes and to 4.27 (95% CI 1.90–9.61, p<0.001) for men between 35–54 y. HRs for all-cause mortality were weaker but reached significance.

Conclusions

We found a high prevalence of ERP in our population-based cohort of middle-aged individuals. ERP was associated with about a 2- to 4-fold increased risk of cardiac mortality in individuals between 35 and 54 y. An inferior localization of ERP was associated with a particularly increased risk. Please see later in the article for the Editors'' Summary     

Mendelian disorders deserve more attention

The study of inherited monogenic diseases has contributed greatly to our mechanistic understanding of pathogenic mutations and gene regulation, and to the development of effective diagnostic tools. But interest has gradually shifted away from monogenic diseases, which collectively affect only a small fraction of the world's population, towards multifactorial, common diseases. The quest for the genetic variability associated with common traits should not be done at the expense of Mendelian disorders, because the latter could still contribute greatly to understanding the aetiology of complex traits.     

Homogeneous and nonradioactive high-throughput screening platform for the characterization of kinase inhibitors in cell lysates

Protein kinases are directly implicated in many human diseases; therefore, kinase inhibitors show great promises as new therapeutic drugs. In an effort to facilitate the screening and the characterization of kinase inhibitors, a novel application of the AlphaScreen technology was developed to monitor JNK activity from (1) purified kinase preparations and (2) endogenous kinase from cell lysates preactivated with different cytokines. The authors confirmed that both adenosine triphosphate (ATP) competitive as well as peptide-based JNK inhibitors were able to block the activity of both recombinant and HepG2 endogenous JNK activity. Using the same luminescence technique adapted for binding studies, the authors characterized peptide inhibitor mechanisms by measuring the binding affinity of the inhibitors for JNK. Because of the versatility of the technology, this cell-based JNK kinase assay could be adapted to other kinases and would represent a powerful tool to evaluate endogenous kinase activity and test a large number of potential inhibitors in a more physiologically relevant environment.     

Embryonic shell formation in the snail Biomphalaria glabrata: a comparison between scanning electron microscopy (SEM) and synchrotron radiation micro computer tomography (SR{micro}CT)

Embryos of different developmental stages and newly hatchedjuveniles of the freshwater snail Biomphalaria glabrata wereinvestigated by synchrotron radiation micro computer tomography(SRµCT). Because this method is sensitive for objectswith a high X-ray density, it is ideally suited to study mineralizedtissues without the need for dissection of the sample, i.e.removal of the soft tissue. This is a clear advantage over scanningelectron microscopy (SEM). However, the resolution is inferiorto SEM (about 1–2 µm compared to a few nm).After the measurement, computer-processed handling (virtualturning, cutting and measuring) of the object is possible. Thedevelopment of the calcified shell in embryos before hatching(age 60, 72, 96 and 120 h after oviposition) was investigatedand both methods were compared. While it was not possible tofind a calcified shell in 60 h old embryos, the shell in72 h old embryos was almost fully mineralized. By SRµCT,the weight of the calcified shell was estimated to 0.64, 9.59and 30.3 µg for embryos of 72, 96 and 120 h.All juvenile snails, of 5 days and 4 weeks after hatching, containedconcretions in the stomach, mostly consisting of calcium phosphate. (Received 10 May 2007; accepted 20 September 2007)     

Dicopper(II) and dinickel(II) complexes of Schiff-base macrocycles derived from 5,5-dimethyl-1,9-diformyldipyrromethane

The synthesis and characterisation of two dicopper(II) and two dinickel(II) macrocyclic complexes, [Cu^II₂L^Pr] (10), [Cu^II₂L^Bu] (11), [Ni^II₂L^Pr] (12) and [Ni^II₂L^Bu] (13), are reported. The two new Schiff-base macrocycles (L^Pr)⁴⁻ and (L^Bu)⁴⁻ are isolated as dimetallic complexes 10-13 by the [2+2] condensation of 5,5-dimethyl-1,9-diformyldipyrromethane (9) and 1,3-diaminopropane or 1,4-diaminobutane, respectively, using Cu²⁺ or Ni²⁺ template ions. Single crystal X-ray structure determinations carried out on 10-13 show that each metal atom is in a square planar N₄ geometry, being bound to two deprotonated pyrrole nitrogen atoms of one dipyrromethane unit and to the two adjacent imine nitrogen atoms. NMR spectra obtained for the two dinickel(II) complexes 12 and 13 show that in CDCl₃ solution they are highly symmetrical and diamagnetic.     

Proteomic signatures: amino acid and oligopeptide compositions differentiate among phyla

Availability of complete genome sequences allows in-depth comparison of single-residue and oligopeptide compositions of the corresponding proteomes. We have used principal component analysis (PCA) to study the landscape of compositional motifs across more than 70 genera from all three superkingdoms. Unexpectedly, the first two principal components clearly differentiate archaea, eubacteria, and eukaryota from each other. In particular, we contrast compositional patterns typical of the three superkingdoms and characterize differences between species and phyla, as well as among patterns shared by all compositional proteomic signatures. These species-specific patterns may even extend to subsets of the entire proteome, such as proteins pertaining to individual yeast chromosomes. We identify factors that affect compositional signatures, such as living habitat, and detect strong eukaryotic preference for homopeptides and palindromic tripeptides. We further detect oligopeptides that are either universally over- or underabundant across the whole proteomic landscape, as well as oligopeptides whose over- or underabundance is phylum- or species-specific. Finally, we report that species composition signatures preserve evolutionary memory, providing a new method to compare phylogenetic relationships among species that avoids problems of sequence alignment and ortholog detection.