Expression of Transketolase like gene 1 (TKTL1) predicts disease-free survival in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy

<p>Abstract</p> <p>Background</p> <p>For patients with locally advanced rectal cancer (LARC) neoadjuvant chemoradiotherapy is recommended as standard therapy. So far, no predictive or prognostic molecular factors for patients undergoing multimodal treatment are established. Increased angiogenesis and altered tumour metabolism as adaption to hypoxic conditions in cancers play an important role in tumour progression and metastasis. Enhanced expression of Vascular-endothelial-growth-factor-receptor <it>(VEGF-R</it>) and Transketolase-like-1 (<it>TKTL1</it>) are related to hypoxic conditions in tumours. In search for potential prognostic molecular markers we investigated the expression of <it>VEGFR-1</it>, <it>VEGFR-2 </it>and <it>TKTL1 </it>in patients with LARC treated with neoadjuvant chemoradiotherapy and cetuximab.</p> <p>Methods</p> <p>Tumour and corresponding normal tissue from pre-therapeutic biopsies of 33 patients (m: 23, f: 10; median age: 61 years) with LARC treated in phase-I and II trials with neoadjuvant chemoradiotherapy (cetuximab, irinotecan, capecitabine in combination with radiotherapy) were analysed by quantitative PCR.</p> <p>Results</p> <p>Significantly higher expression of <it>VEGFR-1/2 </it>was found in tumour tissue in pre-treatment biopsies as well as in resected specimen after neoadjuvant chemoradiotherapy compared to corresponding normal tissue. High <it>TKTL1 </it>expression significantly correlated with disease free survival. None of the markers had influence on early response parameters such as tumour regression grading. There was no correlation of gene expression between the investigated markers.</p> <p>Conclusion</p> <p>High <it>TKTL-1 </it>expression correlates with poor prognosis in terms of 3 year disease-free survival in patients with LARC treated with intensified neoadjuvant chemoradiotherapy and may therefore serve as a molecular prognostic marker which should be further evaluated in randomised clinical trials.</p

Illuminating the life of GPCRs

The investigation of biological systems highly depends on the possibilities that allow scientists to visualize and quantify biomolecules and their related activities in real-time and non-invasively. G-protein coupled receptors represent a family of very dynamic and highly regulated transmembrane proteins that are involved in various important physiological processes. Since their localization is not confined to the cell surface they have been a very attractive "moving target" and the understanding of their intracellular pathways as well as the identified protein-protein-interactions has had implications for therapeutic interventions. Recent and ongoing advances in both the establishment of a variety of labeling methods and the improvement of measuring and analyzing instrumentation, have made fluorescence techniques to an indispensable tool for GPCR imaging. The illumination of their complex life cycle, which includes receptor biosynthesis, membrane targeting, ligand binding, signaling, internalization, recycling and degradation, will provide new insights into the relationship between spatial receptor distribution and function. This review covers the existing technologies to track GPCRs in living cells. Fluorescent ligands, antibodies, auto-fluorescent proteins as well as the evolving technologies for chemical labeling with peptide- and protein-tags are described and their major applications concerning the GPCR life cycle are presented

Alcohol devaluation has dissociable effects on distinct components of alcohol behaviour

Rationale Substance-related behaviour is often viewed as an appetitive behaviour, motivated by the reinforcing effects of the drug. However, there are various indices of substance motivation (e.g. attentional bias, behavioural economic demand, craving) and it is unclear how these are related or whether they play an important role in all types of substance-related behaviour. Objectives (1) To determine the effect of alcohol devaluation on several indices of alcohol motivation and goal-directed and cue-elicited alcohol behaviour. (2) To investigate which components of motivation mediate any effect of devaluation on behaviour. Methods Sixty-two social drinkers gave baseline measures of alcohol craving, behavioural economic demand and choice for alcohol vs. soft drink. Participants tasted alcohol which was either unadulterated (control) or adulterated with a bitter solution (devaluation) before craving and demand were measured again. Alcohol choice was assessed in several phases: extinction (evaluating goal-directed behaviour), in the presence of drink cues (Pavlovian-to-instrumental transfer (PIT, cue-elicited behaviour)), and reacquisition. Attentional bias (AB) was measured by tracking eye movements towards the drink cues during novel PIT trials where both cues were presented. Finally, consumption was evaluated in a taste test. Results Alcohol devaluation reduced alcohol-related demand, AB, alcohol choice in all phases, and consumption. Alcohol cues presented during PIT increased alcohol choice above baseline irrespective of devaluation. AB and demand for alcohol fully mediated the effect of devaluation on alcohol choice during extinction, AB fully mediated the effect on cue-elicited (specific PIT) alcohol choice and alcohol consumption. Conclusions Alcohol behaviour in social drinkers is largely sensitive to devaluation, i.e. governed by current motivational value of the drug (suggesting goal-directed behaviour). However, a dissociable form of stimulus control can also drive alcohol-seeking independently of drug value (specific PIT). Mediation analyses suggests that AB may play a paradoxical role in both forms of alcohol seeking and consumption

The evolution of primate short-term memory

Short-term memory is implicated in a range of cognitive abilities and is critical for understanding primate cognitive evolution. To investigate the effects of phylogeny, ecology and sociality on short-term memory, we tested the largest and most diverse primate sample to date (421 non-human primates across 41 species) in an experimental delayed-response task. Our results confirm previous findings that longer delays decrease memory performance across species and taxa. Our analyses demonstrate a considerable contribution of phylogeny over ecological and social factors on the distribution of short-term memory performance in primates; closely related species had more similar short-term memory abilities. Overall, individuals in the branch of Hominoidea performed better compared to Cercopithecoidea, who in turn performed above Platyrrhini and Strepsirrhini. Interdependencies between phylogeny and socioecology of a given species presented an obstacle to disentangling the effects of each of these factors on the evolution of shortterm memory capacity. However, this study offers an important step forward in understanding the interspecies and individual variation in short-term memory ability by providing the first phylogenetic reconstruction of this trait’s evolutionary history. The dataset constitutes a unique resource for studying the evolution of primate cognition and the role of short-term memory in other cognitive abilities

Violência doméstica e abuso de drogas na gestação Violencia domestica y abuso de drogas en la gestación Domestic violence and drugs abuse in pregnancy

O presente estudo advém da revisão sistemática de publicações científicas indexadas no Medline de 1993 a 2004, objetivando analisar o conhecimento científico sobre violência doméstica e abuso de drogas na gestação. Os 19 artigos analisados estão publicados em periódicos internacionais de especialidades relacionadas, predominantemente, à saúde da criança, sendo a maioria da área médica e de origem americana, todos com o idioma inglês. Desses artigos, 57,9% são estudos descritivos e 42,1% trabalhos teóricos. Abordam temas relacionados às necessidades psicossociais da mulher, importância da responsabilidade paterna na gestação, e os fatores de risco e as implicações na saúde da mulher e da criança associados à violência doméstica e ao uso de drogas. Este embasamento teórico possibilita a intervenção neste cenário.<br>El presente estudio resulta de la revisión sistemática de publicaciones científicas indexadas en Medline de 1993 a 2004, con objeto de analizar el conocimiento científico sobre violencia doméstica y abuso de drogas en la gestación. Los 19 artículos analizados están publicados en periódicos internacionales de especialidades, relacionadas predominantemente a la salud del niño, siendo la mayoría del área médica y de origen americana, todos en el idioma inglés. De esos artículos, el 57,9% corresponde a estudios descriptivos y el 42,1% a trabajos teóricos. Tratan de temas relacionados a las necesidades psicosociales de la mujer, importancia de la responsabilidad paterna en la gestación, y los factores de riesgo y las implicaciones en la salud de la mujer y del niño asociadas a la violencia doméstica y al uso de drogas. Esta fundamentación teórica posibilita intervenir en este escenario.<br>This study results from a systematic review of scientific publications indexed in Medline between 1993 and 2004, aimed at analyzing scientific knowledge about domestic violence and drugs abuse during pregnancy. Nineteen articles were analyzed. These were published in international periodicals, mainly related to the specialty of child health. Most of these were medical periodicals of American origin and all of them published in English. As to study type, 57.9% were descriptive studies and 42.1% theoretical papers. These deal with subjects related to the woman's psychosocial needs, the importance of paternal responsibility in pregnancy, and the risk factors and implications of domestic violence and drugs use on the health of woman and child. This theoretical foundation allows for interventions in this scenario

Changes in Soil Properties and Site Productivity Caused by Red Alder

Red alder (Alnus rubra Bong.) is well recognized as an effective host plant for the symbiotic fixation of N. While this fixation process leads to the rapid accumulation of N within the ecosystem, it also enhances nutrient accumulation in biomass and soil organic matter and increases nitrification and cation leaching. We hypothesized that changes in soil properties resulting from these processes would decrease site productivity for second rotation red alder. Adjacent stands of 55 yr old alder and Douglas fir (Pseudotsuga menziesii [Mirb.] Franco) were studied at the Thompson Research Center on the Cedar River Watershed in western Washington, USA. The presence of red alder oaused the following soil changes: decreased soil solution pH, increased CEC, increased exchangeable acidity accompanied by a decreased soil pH and base saturation. This decreased soil and soil solution pH resulted in increased A1 concentration in the soil solution and on exchange sites as well as decreased P availability. To determine the effect of these changes on the productivity of the 2nd rotation alder forest, a species conversion experiment was initiated 5 yr ago. Results from this conversion study clearly indicated that the first rotation red alder forest has caused a relative decrease in the productivity of the second rotation red alder plantation. Compared to the growth of red alder on the former Douglas fir site, the second rotation red alder on the former red alder site exhibited 33% less height growth and 75% less aboveground biomass accumulation after 5 yr. Future research will focus on identifying those factors causing this lower productivity including P availability, soil acidity and Al toxicity, cation availability, and competition with other vegetation