Peroxisome proliferator-activated receptor mediates cross-talk with thyroid hormone receptor by competition for retinoid X receptor. Possible role of a leucine zipper-like heptad repeat.

The peroxisome proliferator-activated receptors (PPAR) and thyroid hormone receptors (TR) are members of the nuclear receptor superfamily, which regulate lipid metabolism and tissue differentiation. In order to bind to DNA and activate transcription, PPAR requires the formation of heterodimers with the retinoid X receptor (RXR). In addition to activating transcription through its own response elements, PPAR is able to selectively down-regulate the transcriptional activity of TR, but not vitamin D receptor. The molecular basis of this functional interaction has not been fully elucidated. By means of site-directed mutagenesis of hPPAR alpha we mapped its inhibitory action on TR to a leucine zipper-like motif in the ligand binding domain of PPAR, which is highly conserved among all subtypes of this receptor and mediates heterodimerization with RXR. Replacement of a single leucine by arginine at position 433 of hPPAR alpha (L433R) abolished heterodimerization of PPAR with RXR and consequently its trans-activating capacity. However, a similar mutation of a leucine residue to arginine at position 422 showed no alteration of heterodimerization, DNA binding, or transcriptional activation. The dimerization deficient mutant L433R was no longer able to inhibit TR action, demonstrating that the selective inhibitory effect of PPAR results from the competition for RXR as well as possibly for other TR-auxiliary proteins. In contrast, abolition of DNA binding by a mutation in the P-box of PPAR (C122S) did not eliminate the inhibition of TR trans-activation, indicating that competition for DNA binding is not involved. Additionally, no evidence for the formation of PPAR:TR heterodimers was found in co-immunoprecipitation experiments. In summary, we have demonstrated that PPAR selectively inhibits the transcriptional activity of TRs by competition for RXR and possibly non-RXR TR-auxiliary proteins. In contrast, this functional interaction is independent of the formation of PPAR:TR heterodimers or competition for DNA binding.

Workers' perception of workplace bullying: a cross-cultural study

This study is one of the first studies to approach workplace bullying cross-culturally. It sought to compare employees' understanding of workplace bullying in two different world regions: Central America and Southern Europe, regarding three aspects of workplace bullying: psychological vs. physical harassment, hierarchical vs. horizontal bullying, and direct vs. indirect aggression. A convenience sample of 246 workers provided their own definition of workplace bullying through a single, open-ended question. The results showed that employees from Central America emphasized the physical component of workplace bullying more than the Southern European employees. However, similarities in the conceptualization of workplace bullying across both cultures were found as well. Both Southern European and Central American employees defined workplace bullying mainly as a hierarchical phenomenon, where the aggression took the form of direct strategies. Such differences and similarities bring to the field some positive inputs for the development and implementation of different strategies for dealing effectively with this phenomenon.

Full-waveform inversion of cross-hole ground-penetrating radar data to characterize a gravel aquifer close to the Thur River, Switzerland

Cross-hole radar tomography is a useful tool for mapping shallow subsurface electrical properties viz. dielectric permittivity and electrical conductivity. Common practice is to invert cross-hole radar data with ray-based tomographic algorithms using first arrival traveltimes and first cycle amplitudes. However, the resolution of conventional standard ray-based inversion schemes for cross-hole ground-penetrating radar (GPR) is limited because only a fraction of the information contained in the radar data is used. The resolution can be improved significantly by using a full-waveform inversion that considers the entire waveform, or significant parts thereof. A recently developed 2D time-domain vectorial full-waveform crosshole radar inversion code has been modified in the present study by allowing optimized acquisition setups that reduce the acquisition time and computational costs significantly. This is achieved by minimizing the number of transmitter points and maximizing the number of receiver positions. The improved algorithm was employed to invert cross-hole GPR data acquired within a gravel aquifer (4-10 m depth) in the Thur valley, Switzerland. The simulated traces of the final model obtained by the full-waveform inversion fit the observed traces very well in the lower part of the section and reasonably well in the upper part of the section. Compared to the ray-based inversion, the results from the full-waveform inversion show significantly higher resolution images. At either side, 2.5 m distance away from the cross-hole plane, borehole logs were acquired. There is a good correspondence between the conductivity tomograms and the natural gamma logs at the boundary of the gravel layer and the underlying lacustrine clay deposits. Using existing petrophysical models, the inversion results and neutron-neutron logs are converted to porosity. Without any additional calibration, the values obtained for the converted neutron-neutron logs and permittivity results are very close and similar vertical variations can be observed. The full-waveform inversion provides in both cases additional information about the subsurface. Due to the presence of the water table and associated refracted/reflected waves, the upper traces are not well fitted and the upper 2 m in the permittivity and conductivity tomograms are not reliably reconstructed because the unsaturated zone is not incorporated into the inversion domain.

Workers' perception of workplace bullying: a cross-cultural study

This study is one of the first studies to approach workplace bullying cross-culturally. It sought to compare employees' understanding of workplace bullying in two different world regions: Central America and Southern Europe, regarding three aspects of workplace bullying: psychological vs. physical harassment, hierarchical vs. horizontal bullying, and direct vs. indirect aggression. A convenience sample of 246 workers provided their own definition of workplace bullying through a single, open-ended question. The results showed that employees from Central America emphasized the physical component of workplace bullying more than the Southern European employees. However, similarities in the conceptualization of workplace bullying across both cultures were found as well. Both Southern European and Central American employees defined workplace bullying mainly as a hierarchical phenomenon, where the aggression took the form of direct strategies. Such differences and similarities bring to the field some positive inputs for the development and implementation of different strategies for dealing effectively with this phenomenon.

The peroxisome proliferator-activated receptors at the cross-road of diet and hormonal signalling.

The peroxisome proliferator-activated receptors (PPARs) are members of the steroid/thyroid nuclear receptor superfamily of ligand-activated transcription factors. To date, three isotypes have been identified, alpha, beta and gamma, encoded by three different genes. The alpha isotype is expressed at high levels in the liver where it has a role in lipid oxidation. Its expression and activity follow a diurnal rhythm that parallels the circulating levels of corticosterone in the bloodstream. The gamma isotype on the other hand, is mainly expressed in adipose tissue and has a critical role in adipocyte differentiation and lipid storage. The function of the ubiquitously expressed isotype, PPAR beta, remains to be determined. Besides fulfilling different roles in lipid metabolism, the different PPAR isotypes also have different ligand specificities. A new approach to identify ligands was developed based on the ligand-dependent interaction of PPAR with the recently characterized co-activator SRC-1. This so-called CARLA assay has allowed the identification of fatty acids and eicosanoids as PPAR ligands. Although the evidence clearly links PPAR isotypes to distinct functions, the molecular basis for this isotype-specificity is still unclear. All three isotypes are able to bind the same consensus response element, formed by a direct repeat of two AGGTCA hexamers separated by one base, though with different affinities. We recently demonstrated that besides the core DR-1 element, the 5' flanking sequence should be included in the definition of a PPRE. Interestingly, the presence of this flanking sequence is of particular importance in the context of PPAR alpha binding. Moreover, it reflects the polarity of the PPAR-RXR heterodimer on DNA, with PPAR binding to the 5' half-site and RXR binding to the 3' half-site. This unusual polarity may confer unique properties to the bound heterodimer with respect to ligand binding and interaction with co-activators and corepressors.

Cross-cultural clinical competence and post-graduate teaching: any impact(s) on doctors?

Context: Cross-cultural clinical competence (CCC) requires a mixtureof "knowledge" (K), "attitude" (A) and "skills" (S), in order to develop theability to give quality care to patients of different cultures. Theseattributes allow, while providing medical care, consideration of thepatient's medical, social, cultural and language needs. The LausanneUniversity Medical Policlinic (PMU) provides approximately 30000consultations per year to migrant patients and over the past five yearshas implemented a training course on CCC that focuses on trialogue,stereotypes and administrative procedures for the healthcare ofmigrants.Method: A quantitative survey of 18 new residents, was carried outusing a validated questionnaire, the "Multicultural AssessmentQuestionnaire" (the MAQ, 16 questions on K, A and S) to evaluate theimpact of CCC training. The questionnaire was distributed before theCCC course (J-1), three days after (J+3) and three months later (J+90).A descriptive univariate analysis of the difference in MAQ scoresbetween the times J-1 - J+3 and J-1 - J+90 was made. Three FocusGroups were conducted, at three months, to explore residents' thoughtsabout the course.Results: A significant increase was observed in global performancedeclared by residents. Following the intervention, the score of the MAQincreased from 31.4 points to 38.0 points at three days (p = 0.004) andto 37.7 points at three months (p = 0.003). This increase was mostnoticeable in the field of acquiring K: total score J-1: 118, J+3: 189,J+90: 190 (difference J-1 - J+3 and J-1 - J+90: p <0.005). There was nosignificant difference in acquiring A (J-1: 222, J+3: 228, J+90: 229), andS increases in a significant way at first (J-1: 222, J+3: 265, J-1 - J+3:p = 0.035), then comes back to the start value (J+90: 217). The residentswere interested by the course which they felt provides useful informationfor clinical practice. They had a great number of expectations in varyingfields (medical anthropology, cultural differences, epidemiology, etc.),hoping a "ready-made" solution for the approach of migrant patients.Conclusions: A unique training of CCC at the post-graduate level,upgraded K, and to a lesser extent A and S, for these 18 residents. Theywere interest and they had many expectations. Subsequent coursesshould consolidate these acquisitions. Future study should demonstratethe impact on patients' clinical outcome.

Efeitos de doses de nitrogênio na produção de leite de vacas em pastagem de coast-cross

O objetivo do trabalho consistiu em avaliar os efeitos de três doses de nitrogênio (N), 100, 250 e 400 kg/ha/ano, aplicadas em pastagem de coast-cross (Cynodon dactylon (L.) Pers.) sobre a produção de leite em duas lactações de vacas da raça Holandesa. A pastagem foi irrigada na seca e manejada sob pastejo rotativo. O delineamento experimental foi o de blocos ao acaso, em parcelas subdividas (nas parcelas, doses de N; nas subparcelas, fases da lactação), com oito animais por tratamento e duas repetições de área. Os teores de proteína bruta do pasto foram semelhantes (P>0,05) entre os tratamentos. A taxa de lotação da pastagem foi inferior (P<0,05) na menor dose de N. Não foi observada diferença (P>0,05) na produção diária de leite por animal. As produções de leite por área foram mais elevadas (P<0,05) nas duas maiores doses de N. A aplicação de 100 kg/ha/ano de N foi a que proporcionou maior quantidade de leite por quilograma de N.

Nitrogen fertilization impact on agronomic traits of maize hybrids released at different decades

Genetic selection of maize hybrids is often conducted using high N rates during the breeding cycle. This procedure may either lead to the release of genotypes that present nitrogen luxury consumption or require a stronger N input to accomplish their yield potential. This work was carried out to evaluate the effects of N rates on grain yield and N use efficiency of hybrids cultivated in different decades in Southern Brazil. The trial was performed in Lages, Santa Catarina State. A split plot design was used. Hybrids Ag 12, Ag 28, Ag 303 and Ag 9012, released during the 60's, 70's, 80's and 90's, respectively, were evaluated in the main plots. Nitrogen rates equivalent to 0, 50, 100 and 200 kg ha-1 were side-dressed in the split-plots when each hybrid had six fully expanded leaves. Modern-day hybrid Ag 9012 had higher grain yield than hybrids of earlier eras, regardless of N rates. Under high doses of N, the older hybrids Ag 12 and Ag 28 took up more N and presented higher values of shoot dry matter at flowering than Ag 9012. Nonetheless, they set less grains per ear which contributed to decrease their grain yield and N use efficiency.

Efficiency of split nitrogen fertilization with adjusted irrigation on potato

Selostus: Jaetun typpilannoituksen käyttömahdollisuudet perunalle

Harvesting strategy and N fertilization influence ¹³⁴Cs uptake by forage plants

Selostus: Korjuuaika ja typpilannoitus vaikuttavat rehukasvien radiocesiumpitoisuuteen