Circadian Programs of Transcriptional Activation, Signaling, and Protein Turnover Revealed by Microarray Analysis of Mammalian Cells

Many aspects of physiology and behavior are temporally organized into daily 24 hr rhythms, driven by an endogenous circadian clock. Studies in eukaryotes have identified a network of interacting genes forming interlocked autoregulatory feedback loops which underlie overt circadian organization in single cells [1, 2]. While in mammals the master oscillator resides in the suprachiasmatic nuclei of the hypothalamus [2], semiautonomous circadian oscillators also exist in peripheral tissues [3–5] and in immortalized fibroblasts, where rhythmicity is induced following a serum shock [6, 7]. We used this model system in combination with high-density cDNA microarrays to examine the magnitude and quality of clock control of gene expression in mammalian cells. Supported by application of novel bioinformatics tools, we find ∼2% of genes, including expected canonical clock genes, to show consistent rhythmic circadian expression across five independent experiments. Rhythmicity in most of these genes is novel, and they fall into diverse functional groups, highlighted by a predominance of transcription factors, ubiquitin-associated factors, proteasome components, and Ras/MAPK signaling pathway components. When grouped according to phase, 68% of the genes were found to peak during estimated subjective day, 32% during estimated subjective night, with a tendency to peak at a phase corresponding to anticipation of dawn or dusk

Long-term fire resilience of the Ericaceous Belt, Bale Mountains, Ethiopia

Fire is the most frequent disturbance in the Ericaceous Belt (ca 3000–4300 m.a.s.l.), one of the most important plant communities of tropical African mountains. Through resprouting after fire, Erica establishes a positive fire feedback under certain burning regimes. However, present-day human activity in the Bale Mountains of Ethiopia includes fire and grazing systems that may have a negative impact on the resilience of the ericaceous ecosystem. Current knowledge of Erica–fire relationships is based on studies of modern vegetation, lacking a longer time perspective that can shed light on baseline conditions for the fire feedback. We hypothesize that fire has influenced Erica communities in the Bale Mountains at millennial time-scales. To test this, we (1) identify the fire history of the Bale Mountains through a pollen and charcoal record from Garba Guracha, a lake at 3950 m.a.s.l., and (2) describe the long-term bidirectional feedback between wildfire and Erica, which may control the ecosystem's resilience. Our results support fire occurrence in the area since ca 14 000 years ago, with particularly intense burning during the early Holocene, 10.8–6.0 cal ka BP. We show that a positive feedback between Erica abundance and fire occurrence was in operation throughout the Lateglacial and Holocene, and interpret the Ericaceous Belt of the Ethiopian mountains as a long-term fire resilient ecosystem. We propose that controlled burning should be an integral part of landscape management in the Bale Mountains National Park

Revisiting afro-alpine Lake Garba Guracha in the Bale Mountains of Ethiopia:Rationale, chronology, geochemistry, and paleoenvironmental implications

Abstract: Previous paleolimnological studies demonstrated that the sediments of Garba Guracha, situated at 3950 m asl in the afro-alpine zone of the Bale Mountains of Ethiopia, provide a complete Late Glacial and Holocene paleoclimate and environmental archive. We revisited Garba Guracha in order to retrieve new sediment cores and to apply new environmental proxies, e.g. charcoal, diatoms, biomarkers, and stable isotopes. Our chronology is established using 210Pb dating and radiocarbon dating of bulk sedimentary organic matter, bulk n-alkanes, and charcoal. Although bedrock was not reached during coring, basal ages confirm that sedimentation started at the earliest ~ 16 cal kyr BP. The absence of a systematic age offset for the n-alkanes suggests that “pre-aging” is not a prominent issue in this lake, which is characterised by a very small afro-alpine catchment. X-ray fluorescence scans and total organic carbon contents show a prominent transition from minerogenic to organic-rich sediments around 11 cal kyr BP coinciding with the Holocene onset. While an unambiguous terrestrial versus aquatic source identification seems challenging, the n-alkane-based Paq proxy, TOC/N ratios, δ13C values, and the sugar biomarker patterns suggest a predominantly autochthonous organic matter source. Supraregional climate events, such as the African Humid Period, the Younger Dryas (YD), a 6.5 cal kyr BP short drying event, and the 4.2 cal kyr BP transition to overall drier climate are recorded in our archive. The Garba Guracha record suggests that northern hemisphere forcings played a role in the Eastern African highland paleoclimate

Inverse gene expression patterns for macrophage activating hepatotoxicants and peroxisome proliferators in rat liver

Abstract Macrophage activation contributes to adverse effects produced by a number of hepatotoxic compounds. Transcriptional profiles elicited by two macrophage activators, LPS and zymosan A, were compared to those produced by 100 paradigm compounds (mostly hepatotoxicants) using cDNA microarrays. Several hepatotoxicants previously reported to activate liver macrophages produced transcriptional responses similar to LPS and zymosan, and these were used to construct a gene signature profile for macrophage activators in the liver. Measurement of cytokine mRNAs in the same liver samples by RT-PCR independently confirmed that these compounds are associated with macrophage activation. In addition to expected effects on acute phase proteins and metabolic pathways that are regulated by LPS and inflammation, a strong induction was observed for many endoplasmic reticulum-associated stress/chaperone proteins. Additionally, many genes in our macrophage activator signature profile were well-characterized PPARa-induced genes which were repressed by macrophage activators. A shared gene signature profile for peroxisome proliferators was determined using a training set of clofibrate, WY 14643, diethylhexylphthalate, diisononylphthalate, perfluorodecanoic acid, perfluoroheptanoic acid, and perfluorooctanoic acid. The signature profile included macrophage activator-induced genes that were repressed by peroxisome proliferators. NSAIDs comprised an interesting pharmacological class in that some compounds, notably diflunisal, co-clustered with peroxisome proliferators whereas several others co-clustered with macrophage activators, possibly due to endotoxin exposure secondary to their adverse effects on the gastrointestinal system. While much of these data confirmed findings from the literature, the transcriptional patterns detected using this toxicogenomics approach showed relationships between genes and biological pathways requiring complex analysis to be discerned.

Characterization of global microRNA expression reveals oncogenic potential of miR-145 in metastatic colorectal cancer

Background: MicroRNAs (MiRNAs) are short non-coding RNAs that control protein expression through various mechanisms. Their altered expression has been shown to be associated with various cancers. The aim of this study was to profile miRNA expression in colorectal cancer (CRC) and to analyze the function of specific miRNAs in CRC cells. MirVana miRNA Bioarrays were used to determine the miRNA expression profile in eight CRC cell line models, 45 human CRC samples of different stages, and four matched normal colon tissue samples. SW620 CRC cells were stably transduced with miR-143 or miR-145 expression vectors and analyzed in vitro for cell proliferation, cell differentiation and anchorage-independent growth. Signalling pathways associated with differentially expressed miRNAs were identified using a gene set enrichment analysis. Results: The expression analysis of clinical CRC samples identified 37 miRNAs that were differentially expressed between CRC and normal tissue. Furthermore, several of these miRNAs were associated with CRC tumor progression including loss of miR-133a and gain of miR-224. We identified 11 common miRNAs that were differentially expressed between normal colon and CRC in both the cell line models and clinical samples. In vitro functional studies indicated that miR-143 and miR-145 appear to function in opposing manners to either inhibit or augment cell proliferation in a metastatic CRC model. The pathways targeted by miR-143 and miR-145 showed no significant overlap. Furthermore, gene expression analysis of metastatic versus non-metastatic isogenic cell lines indicated that miR-145 targets involved in cell cycle and neuregulin pathways were significantly down-regulated in the metastatic context. Conclusion: MiRNAs showing altered expression at different stages of CRC could be targets for CRC therapies and be further developed as potential diagnostic and prognostic analytes. The identified biological processes and signalling pathways collectively targeted by co-expressed miRNAs in CRC provide a basis for understanding the functional role of miRNAs in cancer. © 2009 Arndt et al; licensee BioMed Central Ltd

Surgical cognitive simulation improves real-world surgical performance: randomized study

Background Despite the acknowledgement of human factors, application of psychological methods by surgeons to improve surgical performance is sparse. This may reflect the paucity of evidence that would help surgeons to use psychological techniques effectively. There is a need for novel approaches to see how cognitive training might be used to address these challenges. Methods Surgical trainees were divided into intervention and control groups. The intervention group received training in surgical cognitive simulation (SCS) and was asked to apply the techniques while working in operating theatres. Both groups underwent procedure-based assessment based on the UK and Ireland Intercollegiate Surgical Curriculum Programme (ISCP) before the training and 4 months afterwards. Subjective evaluations of SCS application were obtained from the intervention group participants. Results Among 21 participants in the study, there was a statistically significant improvement in 11 of 16 procedure-based assessment domains (P < 0.050) as well as a statistically significant mean reduction in time to complete the procedure in the intervention group (–15.98 versus –1.14 min; P = 0.024). Subjectively, the intervention group experienced various benefits with SCS, especially in preoperative preparedness, intraoperative focus, and overall performance. Conclusion SCS training has a statistically significant impact in improving surgical performance. Subjective feedback suggests that surgeons are able to apply it in practice. SCS may prove a vital adjunct for skill acquisition in surgical training

O du verfluchtes Gesindel! : kleine Erinnerungen aus dem Leben eines kleines Komödianten, wirklich Erlebtes und Gesammeltes

von Anton Bittne

The Units of Living

Bittner R. The Units of Living. In: Leist A, ed. Action in Context. Berlin: de Gruyter; 2007: 261-274

Modelling of Technology Valuation in the Process of its Commercialization

Commercialization processes are modeled and analyzed from the point of view of the implementation of activities under particular stages. These issues are the subject of many studies and analyzes, which is why the extensive literature is available on this subject. Technology valuation at various stages of the commercialization process is a separate issue. Such valuation is prepared in most cases by consulting companies for determining the price in the buying and selling processes. These valuations use known methods also used in other cases, e.g., real estate valuation. The work carried out presents the author’s concept of the commercialization process model, taking into account the costs and value of the technology at various stages of the product life cycle. The model uses a stochastic approach to determine future revenues and costs, which allows estimating the value of the technology by or in determining the probability of assessment validity. The proposed stochastic approach greatly increases the chances of using the presented solutions in practical activities related to technology valuation for the purposes of purchase and sale transactions