Self-peptide released from class II HLA-DR1 exhibits a hydrophobic two-residue contact motif.

Peptide fragments of foreign and self-proteins are of great immunologic importance as their binding to major histocompatibility complex (MHC) class I or II molecules makes an interaction with a corresponding T cell receptor possible. Recently, allele-specific peptide sequence motifs proved to be responsible for MHC binding, no matter whether self- or non-self-antigens were involved. Up to now, all investigated human class II-associated peptides were derived from foreign antigenic proteins. Therefore, we undertook sequence and binding analyses with a 16-mer self-peptide (SP3) that has been eluted from HLA-DR1. Here we demonstrate, by synthetic polyalanine-based 13-mer analogues of SP3, that two bulky hydrophobic anchor residues with relative spacing i, i + 8 are sufficient for high affinity binding. This is consistent with the hydrophobic i, i + 8 binding pattern recently found for DR-restricted T cell epitopes. Nevertheless, highly helical alanine-based design peptides with anchor spacing i, i + 9 exhibit maximal affinity, whereas replacement of alanine by helix destabilizing proline abrogates binding. Thus, a two-residue contact motif is the common minimal requirement of self- and foreign peptides for high affinity anchoring to HLA-DR1. In contrast to class I, the anchor spacing of DR1-associated peptides seems to bear some variability due to conformational diversity.

Strong hydroclimatic controls on vulnerability to subsurface nitrate contamination across Europe.

Subsurface contamination due to excessive nutrient surpluses is a persistent and widespread problem in agricultural areas across Europe. The vulnerability of a particular location to pollution from reactive solutes, such as nitrate, is determined by the interplay between hydrologic transport and biogeochemical transformations. Current studies on the controls of subsurface vulnerability do not consider the transient behaviour of transport dynamics in the root zone. Here, using state-of-the-art hydrologic simulations driven by observed hydroclimatic forcing, we demonstrate the strong spatiotemporal heterogeneity of hydrologic transport dynamics and reveal that these dynamics are primarily controlled by the hydroclimatic gradient of the aridity index across Europe. Contrasting the space-time dynamics of transport times with reactive timescales of denitrification in soil indicate that ~75% of the cultivated areas across Europe are potentially vulnerable to nitrate leaching for at least one-third of the year. We find that neglecting the transient nature of transport and reaction timescale results in a great underestimation of the extent of vulnerable regions by almost 50%. Therefore, future vulnerability and risk assessment studies must account for the transient behaviour of transport and biogeochemical transformation processes.

Hormonal modulation of plant growth: the role of auxin perception.

The organisation of growth and development in vascular plants appears to be highly adapted to meet the specific demands of a sessile, autotrophic habit. Many of the characteristic features of plant development are associated with the activities of five groups of phytohormones. Each of the phytohormones has the ability to influence fundamentally a remarkable variety of developmental and physiological processes. This ability has been widely documented but remains to be explained. Here we describe how recent breakthroughs in the analysis and understanding of eucaryotic signal transduction are being applied, in conjunction with technical advances in molecular genetics, to elucidate the molecular basis of the phytohormonal properties of auxin. Both auxin concentration, and the sensitivity of plant cells to this phytohormone have been implicated as important parameters in auxin action. We describe recent molecular biological approaches to assess the contribution made by each of these parameters. Emphasis is given to a description of recent genetic and biochemical progress towards identification of the molecular targets of the auxin signal and the molecular components involved in its subsequent transduction.

Developments and improvements in the manufacturing of human therapeutics with mammalian cell cultures.

During recent years, biopharmaceutical products manufactured by processes that use mammalian cell cultures have gained increasing importance. At the same time, a strong awareness of the importance of the safety and quality of such products has also emerged. This has led to improvements in cultivation and production technology, validation procedures and process organization.

Down regulation of S-adenosyl-L-methionine decarboxylase activity of Trypanosoma brucei during transition from long slender to short stumpy-like forms in axenic culture.

Long slender trypanosomes, isolated from infected mouse blood or from cryopreserved stabilates, respectively, were unable to grow in conditioned media (cMEM), prepared from the declining phase of axenic bloodstream form cultures. Additionally, mixtures of fresh medium and cMEM led to decreased growth rates and, in accordance to the amount of cMEM used, to a decreased S-adenosyl-L-methionine decarboxylase (Ado-MetDC; E.C. 4.1.1.50) activity. Since addition of polyamines could not overcome the process of transition from dividing to non-dividing cells and the intracellular S-adenosyl-L-methionine (AdoMet), ornithine and putrescine concentrations seemed unaltered during the course of cultivation, we questioned if polyamine metabolism is involved in this transition process. Activities of two key enzymes of polyamine metabolism, AdoMetDC and ornithine decarboxylase (ODC; E.C. 4.1.1.17) were therefore monitored during different growth stages. Our results revealed a specific activity of 44 pmol min-1 mg protein-1 for AdoMetDC and a KM of 10 mu M for AdoMet. Methylglyoxal bis(guanylhydrazone) showed a Ki of 6 mu M. The constant activity of the enzyme during a 7 h time-course in the presence of cycloheximide indicates a t1/2 of more than 7 h for the trypanosomal enzyme. Enzyme activity in trypanosomes isolated from infected laboratory animals and from logarithmic phase bloodstream or procyclic form cultures was high according to a high dividing rate, whereas enzyme activity in parasites isolated from the stationary phase of bloodstream from culture was negligible. In these cultures, AdoMetDC activity decreased with a t1/2 of 7 h during transition from long slender to short stumpy-like forms as soon as the stationary phase was reached. ODC activity was high (approximately 300 pmol min-1 mg protein-1) in dividing trypanosomes isolated from infected animals as well as from logarithmic phase bloodstream or procyclic form cultures and decreased also during transition with a t1/2 of 10 h.

A novel cultivation technique for long-term maintenance of bloodstream form trypanosomes in vitro.

We used an axenic cultivation system to grow African trypanosomes in vitro. Long-term cultivation for more than 60 days has been achieved by replacing the culture medium at regular intervals between 6 and 48 h. In contrast to a control culture without medium replacement, increasing amounts of maximum cell concentrations have been obtained, ranging from 5 x 10(6) to 2 x 10(7) trypanosomes ml-1, whereas the generation doubling time remained constant (about 6 h). Higher cell concentrations have only been obtained by total medium replacement; neither addition of fresh medium nor serum led to a higher cell yield, suggesting that a trypanosome-derived factor or metabolite accumulated in the medium rather than medium was depleted of an essential nutrient. Most interestingly, however, successive waves have been obtained which eventually led to a damped oscillation curve with a constant high population density after about 40 days of cultivation. Cultures were started with a homogeneous population of the long-slender form. As judged by light microscopy, cells showed a stumpy morphology during the declining phase and became slender again in the following growth phase. At later time points, when cells remained in a stationary phase at high population density, many different morphological stages have been observed, similar to those described by early authors as intermediate forms [Ormerod, W. E. (1979) In: Biology of the Kinetoplastida, Vol. 2, pp. 340-393], although many dividing forms are still present at that time. In contrast, identically treated procyclic cultures were unable to produce cyclic growth waves. Based on these results, a novel concept considering a possible differentiation mechanism is discussed.

Verbal and visual causal arguments.

The present paper analyzes how verbalizations and visualizations can be used to justify and dispute causal claims. The analysis is based on a taxonomy of 27 causal arguments as they appear in ordinary language. It is shown how arguments from spatio-temporal contiguity, covariation, counterfactual necessity, and causal mechanisms, to name only a few, are visualized in persuasive uses of tables, graphs, time series, causal diagrams, drawings, maps, animations, photos, movies, and simulations. The discussion centers on how these visual media limit the argumentative moves of justifying, disputing, and qualifying claims; how they constrain the representation of observational, explanatory, and abstract knowledge in the premises of causal arguments; and how they support and externalize argument-specific inferences, namely generalizations, comparisons, mental simulations, and causal explanations.

The protective effects of a new preparation on wound edges.

OBJECTIVE: This study investigated the effect of Cavilon No Sting Barrier Film (NSBF) (3M Healthcare) on erythema on the edges of highly exuding wounds in patients with venous stasis ulcers. METHOD: An intra-individual double-blind randomised test was performed on 239 patients. The two sides of each wound on each patient were treated with two different dressings: Cavilon NSBF was applied to the wound edges of one side and a control (water) to the edges of the other. Erythema was assessed daily using a chromameter. RESULTS: These are based on the 227 patients who completed the study. The researchers were surprised by their unambiguity: in 88.1% of patients, the erythema completely disappeared within three days of treatment with the test material; in the remaining 11.9% it had completely disappeared after four days. With the control, erythema intensity remained more or less unchanged throughout the four-day observation period. CONCLUSION: This study demonstrates that Cavilon NSBF helped control erythema in all the patients: in 97.3% examined, the measurable and objectively recordable erythema receded within two days.

Effects of emotion-related surface similarity in analogical problem solving.

In analogical problem solving, a source problem with a known solution is used to solve a target problem. The present study deals with one possible condition influencing the search for possible source problems (i.e., with similarities between source and target problems in the emotional connotation of the problem cover stories). Subjects were given six source problems-distractors as well as target-relevant problems-that were varied with respect to the emotional valence of the cover stories. Then one group of subjects (n = 32) was given a pleasant target problem, while the other group (n = 31) received an unpleasant target problem. Except for emotional valence the two target problems were identical. Subjects preferred those target-relevant source problems that were emotionally congruent with the target problem. The findings are interpreted within network theories of long-term memory, introducing emotional markers or emotion-concept nodes to represent the emotional connotation of the represented units. By controlling subjects' mood change after reading the (un)pleasant target-problem cover story, it could be ruled out that the observed results were due to a mood congruity effect of the type described by Bower (1981).

Implicit and explicit dialogue structuring in virtual learning groups.

BACKGROUND: The promotion of virtual learning groups by instructional means is gaining importance with the spread of telematic learning. In virtual learning groups, students discuss certain learning materials or cooperate in problem solving by means of computer-mediated communication. Due to the specific features of electronic communication, supportive means appear to be necessary for such learning situations. AIMS: The investigation focuses on testing two different forms of dialogue structuring in virtual learning groups, in which students discuss a given subject matter together and clarify problems in understanding by means of synchronous computer-mediated communication. SAMPLE: Forty-five students from various disciplines at the University of Tübingen, except students of physics, participated in the investigation. METHOD: An experiment was conducted involving three-person groups in a telematic setting with two different kinds of dialogue structuring: implicit structuring induced group discussion on the subject matter by working on key questions in a preceding learning phase, whilst explicit structuring provided additional rules for discussion. These rules prompted group members to argue and aimed at directing them to equal participation. RESULTS: Compared to a control group, both implicit and explicit structuring showed greater orientation on the subject matter and showed less off-task talk. Moreover, explicit structuring led to more coherence in subject matter discussion with regard to the completion of topics. However, post-test performance showed no significant difference in knowledge over that of the control group. CONCLUSION: The results of the investigation show that dialogue structuring can be an adequate pedagogical approach for virtual learning groups.

[Possibilities for integration of emotions in theoretical principles of cognitive psychology]. / Möglichkeiten der Integration von Emotionen in theoretische Ansätze der Kognitionspsychologie.

Different approaches to integrate emotion and cognition can be differentiated. On the one hand emotions can be part of an associative network of long-term memory (Bower, 1981; Bower & Cohen, 1982; Lang, 1979, 1984). On the other hand emotions are said to function as mediators that instigate different processing strategies (Fiedler, 1988; Isen, 1984, 1987; Kuhl, 1983 b). Both approaches can be integrated within the framework of ACT* (Anderson, 1983) assuming emotion nodes as parts of the declarative memory and emotion related productions as parts of the procedural memory (Spies & Hesse, 1986). A third approach claims that emotions change the amount of processing capacity available for task related processes (Ellis & Ashbrook, 1988; Kuhl, 1983 b; Spies & Hesse, 1986). The theoretical positions as well as related empirical results are discussed by referring to the literature as well as to some of our own data.

Emotional influences on semantic priming.

Influences of mood on qualitative aspects of cognitive processing are examined within a semantic priming paradigm. The priming effect reflects the reduction of latency for a lexical decision task when a target word is presented in combination with an associatively related prime word. The effect was higher for subjects in whom positive affect had been induced than for a control group, if prime and target were high-associatively related. There was no effect of mood on priming for low-associatively related prime-target pairs. The results are interpreted in terms of a general facilitating influence of mood on spreading activation independent of the affective quality of the processed material.

[Body image of the male athlete. A study of the psychological health of wrestlers and rowers of the lower weight class]. / Das Körpererleben männlicher Sportler. Eine Untersuchung zur psychischen Gesundheit von Ringern und Ruderern der unteren Gewichtsklassen.

The present study reports findings concerning the body-experience of male athletes. 25 wrestlers and 59 rowers in the lower weight categories were investigated using the questionnaire for evaluation of body-experience "Fragebogen zur Beurteilung des eigenen Körpers--FBK" (Strauss u. Appelt, 1983). Due to nature of their sports, these men are particularly subject to a constant pressure to maintain a low body weight. In 31% of the subjects the FBK profiles were indicative of disturbances of body-image and body-experience. This subgroup also demonstrated multiple pathologically elevated scores in the personality questionnaire "Freiburger Persönlichkeitsinventar" (Fahrenberger et al. 1984) and the Eating-Disorder-Inventory (Garner et al. 1983). Low-weight wrestlers and rowers should be considered a high-risk male population for body-image disturbances and other psychological disorders. The casual relationship between the specific sport and the development of an body-image disorder is discussed.

Subclinical eating disorders in male athletes. A study of the low weight category in rowers and wrestlers.

This study investigated the possibility that male athletes who, owing to the rules of their sport, are pressured to maintain a low weight show an elevated prevalence of subclinical eating disorders. Twenty-five wrestlers and 59 rowers in the lower weight categories were investigated using the Eating Disorder Inventory (EDI). Fifty-two percent of the athletes reported the occurrence of binging. The EDI profiles of 11% of the athletes suggested the presence of a subclinical eating disorder. These figures are clearly elevated compared with the normal male population. Low-weight wrestlers and rowers should be considered a high-risk male population for subclinical eating disorders. These findings are comparable to high-risk groups consisting mainly of women (such as ballet and modelling students). The causal relationship between the specific sport and the development of a psychogenic eating disorder is discussed.

Do film cuts facilitate the perceptual and cognitive organization of activity sequences?

Film depictions of activities possess two kinds of structures--namely, the structural features of the depicted activities themselves and a formal structure defined by film cuts. The former structure is used by everyday observers for perceptually and cognitively unitizing the continuous flow of events into comprehensible entities. It seems conceivable that cuts can serve a similar unitizing purpose for film viewers. For each of two different activity sequences, two film versions were produced. Throughout each film version, cuts were placed either at breakpoints or at nonbreakpoints. In a 2 x 2 (activity sequence x film version) factorial design, 40 subjects segmented the film during viewing and recalled the film content after viewing in a detailed protocol. Segmentation behavior depended primarily on the occurrence of breakpoints and was largely unaffected by the occurrence of cuts. Cuts accompanying a breakpoint lead to more detailed recall protocols for these sections of the film.

[Experimental induction of emotional states--does addition of music improve self disclosure?]. / Experimentelle Induktion emotionaler Zustände--Verbessert die zusätzliche Darbietung von Musik die Wirksamkeit selbstbezogener Aussagen?

Two procedures to experimentally induce negative and neutral emotional states are compared: self-referent emotional statements (Velten, 1968) presented alone vs. combined with music. For female subjects selected according to their baseline mood, it could be shown that negative statements alone induced anger whereas in combination with music they evoked sadness, i.e. dependent on the procedure applied, the quality of the induced negative emotion changed. For the induction of a neutral state the combined procedure proved to be superior, especially to reduce a positive baseline mood.