The Pristionchus pacificus genome provides a unique perspective on nematode lifestyle and parasitism

Here we present a draft genome sequence of the nematode Pristionchus pacificus, a species that is associated with beetles and is used as a model system in evolutionary biology. With 169 Mb and 23,500 predicted protein-coding genes, the P. pacificus genome is larger than those of Caenorhabditis elegans and the human parasite Brugia malayi. Compared to C. elegans, the P. pacificus genome has more genes encoding cytochrome P450 enzymes, glucosyltransferases, sulfotransferases and ABC transporters, many of which were experimentally validated. The P. pacificus genome contains genes encoding cellulase and diapausin, and cellulase activity is found in P. pacificus secretions, indicating that cellulases can be found in nematodes beyond plant parasites. The relatively higher number of detoxification and degradation enzymes in P. pacificus is consistent with its necromenic lifestyle and might represent a preadaptation for parasitism. Thus, comparative genomics analysis of three ecologically distinct nematodes offers a unique opportunity to investigate the association between genome structure and lifestyle.     

Proliferation status defines functional properties of endothelial cells

Homeostasis of solid tissue is characterized by a low proliferative activity of differentiated cells while special conditions like tissue damage induce regeneration and proliferation. For some cell types it has been shown that various tissue-specific functions are missing in the proliferating state, raising the possibility that their proliferation is not compatible with a fully differentiated state. While endothelial cells are important players in regenerating tissue as well as in the vascularization of tumors, the impact of proliferation on their features remains elusive. To examine cell features in dependence of proliferation, we established human endothelial cell lines in which proliferation is tightly controlled by a doxycycline-dependent, synthetic regulatory unit. We observed that uptake of macromolecules and establishment of cell–cell contacts was more pronounced in the growth-arrested state. Tube-like structures were formed in vitro in both proliferating and non-proliferating conditions. However, functional vessel formation upon transplantation into immune-compromised mice was restricted to the proliferative state. Kaposi’s sarcoma-associated herpes virus (KSHV) infection resulted in reduced expression of endothelial markers. Upon transplantation of infected cells, drastic differences were observed: proliferation arrested cells acquired a high migratory activity while the proliferating counterparts established a tumor-like phenotype, similar to Kaposi Sarcoma lesions. The study gives evidence that proliferation governs endothelial functions. This suggests that several endothelial functions are differentially expressed during angiogenesis. Moreover, since proliferation defines the functional properties of cells upon infection with KSHV, this process crucially affects the fate of virus-infected cells.     

In-situ cosmogenic 36Cl denudation rates of carbonates in Guizhou karst area

This study quantifies surface denudation of carbonate rocks by the first application of in-situ cosmogenic36Cl in China. Concentrations of natural Cl and in-situ cosmogenic36Cl in bare carbonates from Guizhou karst areas were measured with isotope dilution by accelerator mass spectrometer. The Cl concentration varied from 16 to 206 ppm. The 36Cl concentrations were in range of (0.8-2.4)106 atom g-1 , resulting in total denudation rates of 20-50 mm ka-1 that averaged over a 104-105 a timescale. The 36Cl-denudation rates showed roughly a negative correlation with the local mean temperature. This preliminary observation may suggest the variations of proportions of chemical weathering and physical erosion in denudation process, depending upon local climatic conditions.     

Non-caspase proteases: triggers or amplifiers of apoptosis?

Caspases are the most important effectors of apoptosis, the major form of programmed cell death (PCD) in multicellular organisms. This is best reflected by the appearance of serious development defects in mice deficient for caspase-8, -9, and -3. Meanwhile, caspase-independent PCD, mediated by other proteases or signaling components has been described in numerous publications. Although we do not doubt that such cell death exists, we propose that it has evolved later during evolution and is most likely not designed to execute, but to amplify and speed-up caspase-dependent cell death. This review shall provide evidence for such a concept.     

Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status

Genes of the RAF family encode kinases that are regulated by Ras and mediate cellular responses to growth signals. Activating mutations in one RAF gene, BRAF, have been found in a high proportion of melanomas and in a small fraction of other cancers. Here we show that BRAF mutations in colorectal cancers occur only in tumours that do not carry mutations in a RAS gene known as KRAS, and that BRAF mutation is linked to the proficiency of these tumours in repairing mismatched bases in DNA. Our results not only provide genetic support for the idea that mutations in BRAF and KRAS exert equivalent effects in tumorigenesis, but also emphasize the role of repair processes in establishing the mutation spectra that underpin human cancer.     

Inactivation of hCDC4 can cause chromosomal instability

Aneuploidy, an abnormal chromosome number, has been recognized as a hallmark of human cancer for nearly a century; however, the mechanisms responsible for this abnormality have remained elusive. Here we report the identification of mutations in hCDC4 (also known as Fbw7 or Archipelago) in both human colorectal cancers and their precursor lesions. We show that genetic inactivation of hCDC4, by means of targeted disruption of the gene in karyotypically stable colorectal cancer cells, results in a striking phenotype associated with micronuclei and chromosomal instability. This phenotype can be traced to a defect in the execution of metaphase and subsequent transmission of chromosomes, and is dependent on cyclin E--a protein that is regulated by hCDC4 (refs 2-4). Our data suggest that chromosomal instability is caused by specific genetic alterations in a large fraction of human cancers and can occur before malignant conversion.     

On The Impossibility Of Empirical Controls Of Scientific Theories – From The Point Of View Of A Psychologist

Standard considerations of philosophy of science are reformulated in psychological terms and arguments, suggesting a fundamental change in life perspective: subjective experiences or introspective data are subject to motivational biases and therefore not admitted as objective empirical facts in science, However, we never experience objects or events of the external world, i.e., so called objective facts, but exclusively subjective percepts or mental events. They are merely assumed to, but may or may not be accurate or distorted mental representations of objects or events of an external world. Accordingly, the latter are theoretical constructs, i.e., constructs of the fictitious but most successful predictive (implicit) theory, called external world, which seems to be constructed from regularities observed in mental events and serves as a reference fiction for, erroneously called empirical, tests of predictions of scientific theories.Relevant Publication: Micko, H.C.: 2001, Psychologie: Von der Geistes – zur Naturwissenschaft – und weiter wohin? Erkenntnistheoretische Erwägungen vor und nach dem Aufkommen des philosophischen Konstruktivismus. Ztschr. f. Psychologie, 209: 54–68.     

The role of increasing temperature variability in European summer heatwaves

Instrumental observations and reconstructions of global and hemispheric temperature evolution reveal a pronounced warming during the past approximately 150 years. One expression of this warming is the observed increase in the occurrence of heatwaves. Conceptually this increase is understood as a shift of the statistical distribution towards warmer temperatures, while changes in the width of the distribution are often considered small. Here we show that this framework fails to explain the record-breaking central European summer temperatures in 2003, although it is consistent with observations from previous years. We find that an event like that of summer 2003 is statistically extremely unlikely, even when the observed warming is taken into account. We propose that a regime with an increased variability of temperatures (in addition to increases in mean temperature) may be able to account for summer 2003. To test this proposal, we simulate possible future European climate with a regional climate model in a scenario with increased atmospheric greenhouse-gas concentrations, and find that temperature variability increases by up to 100%, with maximum changes in central and eastern Europe.     

Topography and synaptic shaping of direction selectivity in primary auditory cortex

The direction of frequency-modulated (FM) sweeps is an important temporal cue in animal and human communication. FM direction-selective neurons are found in the primary auditory cortex (A1), but their topography and the mechanisms underlying their selectivity remain largely unknown. Here we report that in the rat A1, direction selectivity is topographically ordered in parallel with characteristic frequency (CF): low CF neurons preferred upward sweeps, whereas high CF neurons preferred downward sweeps. The asymmetry of 'inhibitory sidebands', suppressive regions flanking the tonal receptive field (TRF) of the spike response, also co-varied with CF. In vivo whole-cell recordings showed that the direction selectivity already present in the synaptic inputs was enhanced by cortical synaptic inhibition, which suppressed the synaptic excitation of the non-preferred direction more than that of the preferred. The excitatory and inhibitory synaptic TRFs had identical spectral tuning, but with inhibition delayed relative to excitation. The spectral asymmetry of the synaptic TRFs co-varied with CF, as had direction selectivity and sideband asymmetry, and thus suggested a synaptic mechanism for the shaping of FM direction selectivity and its topographic ordering.