Joining forces toward proactive elephant and rhinoceros conservation.

Proactive approaches that anticipate the long-term effects of current and future conservation threats could increase the effectiveness and efficiency of biodiversity conservation. However, such approaches can be obstructed by a lack of knowledge of habitat requirements for wildlife. To aggregate and assess the suitability of current information available on habitat requirements needed for proactive conservation, we conducted a systematic review of the literature on elephant and rhinoceros habitat requirements and synthesized data by combining a vote counting assessment with bibliometric and term maps. We contextualized these numeric and terminological results with a narrative review. We mapped current methods, results, terminology, and collaborations of 693 studies. Quantitative evidence for factors that influence the suitability of an area for elephants and rhinoceros was biased toward African savanna elephants and ecological variables. Less than one third of holistic approaches considered equal amounts of ecological and anthropogenic variables in their assessments. There was a general lack of quantitative evidence for direct proxies of anthropogenic variables that were expected to play an important role based on qualitative evidence and policy documents. However, there was evidence for a segregation in conceptual frameworks among countries and species and between science versus policy literature. There was also evidence of unused potential for collaborations among southern hemisphere researchers. Our results indicated that the success of proactive conservation interventions can be increased if ecological and anthropogenic dimensions are integrated into holistic habitat assessments and holistic carrying capacities and quantitative evidence for anthropogenic variables is improved. To avoid wasting limited resources, it is necessary to form inclusive collaborations within and across networks of researchers studying different species across regional and continental borders and in the science-policy realm.

Colaboración de Fuerzas hacia la Conservación Proactiva de Elefantes y Rinocerontes Resumen Los enfoques proactivos que anticipan los efectos a largo plazo de las amenazas a la conservación actuales y futuras podrían incrementar la efectividad y la eficiencia de la conservación de la biodiversidad. Sin embargo, dichos enfoques pueden ser frenados por una falta de conocimiento de los requerimientos de hábitat para la vida silvestre. Para sumar y evaluar la idoneidad de la información disponible sobre los requerimientos del hábitat necesitados para la conservación proactiva realizamos una revisión sistemática de la literatura sobre los requerimientos de hábitat de los elefantes y rinocerontes y sintetizamos los datos combinándolos en una evaluación de conteo de votos con mapas bibliométricos y de términos. Contextualizamos estos resultados numéricos y terminológicos con una revisión narrativa. Mapeamos los métodos, resultados, terminologías y colaboraciones actuales de 693 estudios. La evidencia cuantitativa de los factores que influyen sobre la idoneidad de un área para los elefantes y los rinocerontes estuvo sesgada hacia los elefantes de la sabana africana y las variables ecológicas. Menos de un tercio de las estrategias holísticas consideró cantidades iguales de variables ecológicas y antropogénicas en sus evaluaciones. Hubo una carencia generalizada de evidencias cuantitativas para los indicadores directos de las variables antropogénicas que se esperaba tendrían un papel importante con base en la evidencia cualitativa y los documentos de las políticas. Sin embargo, hubo evidencias de una segregación en el marco conceptual entre los países y las especies y entre la ciencia versus la literatura política. También hubo evidencias de un potencial sin explotar para las colaboraciones entre los investigadores del hemisferio sur. Nuestros resultados indicaron que el éxito de las intervenciones de conservación proactiva puede incrementarse si las dimensiones ecológicas y antropogénicas se integran a las evaluaciones holísticas del hábitat y si se mejoran las capacidades de carga holísticas y las evidencias cuantitativas de las variables antropogénicas. Para evitar gastar los recursos limitados, es necesario formar colaboraciones inclusivas dentro y a lo largo de las redes de investigadores que están estudiando a diferentes especies en las fronteras regionales y continentales y dentro del ámbito de la ciencia política.

Exploring movement decisions: Can Bayesian movement-state models explain crop consumption behaviour in elephants (Loxodonta africana)?

Animal movements towards goals or targets are based upon either maximization of resource acquisition or risk avoidance, and the way animals move can reveal information about their motivation. We use hidden Markov models (HMMs) fitted in a Bayesian framework and hourly Global Positioning System fixes to distinguish animal movements into distinct states and analyse the influence of environmental variables on being in, and switching to, a particular state. Specifically, we apply our models to understand elephant movement decisions around agricultural fields, and crop consumption. As it is unclear what the role of habitat features are on this complex process, we analyse whether elephants target agricultural crops for consumption, or simply pass through them in search of water. Our HMMs separate elephant movements into two states: exploratory movements that are fast and directional, and encamped movements that are slow and meandering. For each elephant, we ran 16 models with each possible combination of selected habitat features (river, elephant corridor, agricultural field, trees), and repeated these analyses including interaction effects with both season and time of day. We used cross-validation to select the best model. In corridors, exploratory movements are dominant. Elephants mainly showed encamped movements at the river during the dry season, when temporary water sources have dried out and elephants relied on this permanent water source. In fields, males most often exhibited exploratory movements to and from the river, while females showed an increase in the frequency of encamped behaviour during the dry season and at night-the times when most crop consumption and movements through fields occur. Adaptation to risk could explain this behaviour, since foraging in fields is likely less risky under the cover of darkness and during the dry season when farmers are absent. This sex segregation in elephant movement decisions highlights the importance of predation risk in shaping movement patterns, which can result in sex segregation in responses to mitigation methods. The increase in encamped movements in the dry season suggests the importance of agricultural timing, and shows the potential for early ploughing and early-harvest crop types in order to reduce elephant crop consumption. Taking this into account could increase efficiency of elephant crop consumption mitigation.

Stress leads to aberrant hippocampal involvement when processing schema-related information.

Prior knowledge, represented as a mental schema, has critical impact on how we organize, interpret, and process incoming information. Recent findings indicate that the use of an existing schema is coordinated by the medial prefrontal cortex (mPFC), communicating with parietal areas. The hippocampus, however, is crucial for encoding schema-unrelated information but not for schema-related information. A recent study indicated that stress mediators may affect schema-related memory, but the underlying neural mechanisms are currently unknown. Here, we thus tested the impact of acute stress on neural processing of schema-related information. We exposed healthy participants to a stress or control manipulation before they processed, in the MRI scanner, words related or unrelated to a preexisting schema activated by a specific cue. Participants' memory for the presented material was tested 3-5 d after encoding. Overall, the processing of schema-related information activated the mPFC, the precuneus, and the angular gyrus. Stress resulted in aberrant hippocampal activity and connectivity while participants processed schema-related information. This aberrant engagement of the hippocampus was linked to altered subsequent memory. These findings suggest that stress may interfere with the efficient use of prior knowledge during encoding and may have important practical implications, in particular for educational settings.

Stress affects the neural ensemble for integrating new information and prior knowledge.

Prior knowledge, represented as a schema, facilitates memory encoding. This schema-related learning is assumed to rely on the medial prefrontal cortex (mPFC) that rapidly integrates new information into the schema, whereas schema-incongruent or novel information is encoded by the hippocampus. Stress is a powerful modulator of prefrontal and hippocampal functioning and first studies suggest a stress-induced deficit of schema-related learning. However, the underlying neural mechanism is currently unknown. To investigate the neural basis of a stress-induced schema-related learning impairment, participants first acquired a schema. One day later, they underwent a stress induction or a control procedure before learning schema-related and novel information in the MRI scanner. In line with previous studies, learning schema-related compared to novel information activated the mPFC, angular gyrus, and precuneus. Stress, however, affected the neural ensemble activated during learning. Whereas the control group distinguished between sets of brain regions for related and novel information, stressed individuals engaged the hippocampus even when a relevant schema was present. Additionally, stressed participants displayed aberrant functional connectivity between brain regions involved in schema processing when encoding novel information. The failure to segregate functional connectivity patterns depending on the presence of prior knowledge was linked to impaired performance after stress. Our results show that stress affects the neural ensemble underlying the efficient use of schemas during learning. These findings may have relevant implications for clinical and educational settings.

How acute stress may enhance subsequent memory for threat stimuli outside the focus of attention: DLPFC-amygdala decoupling.

Stress-related disorders, e.g., anxiety and depression, are characterized by decreased top-down control for distracting information, as well as a memory bias for threatening information. However, it is unclear how acute stress biases mnemonic encoding and leads to prioritized storage of threat-related information even if outside the focus of attention. In the current study, healthy adults (N = 53, all male) were randomly assigned to stress induction using the socially evaluated cold-pressor test (SECPT) or a control condition. Participants performed a task in which they were required to identify a target letter within a string of letters that were either identical to the target and thereby facilitating detection (low distractor load) or mixed with other letters to complicate the search (high load). Either a fearful or neutral face was presented on the background, outside the focus of attention. Twenty-four hours later, participants were asked to perform a surprise recognition memory test for those background faces. Stress induction resulted in increased cortisol and negative subjective mood ratings. Stress did not affect visual search performance, however, participants in the stress group showed stronger memory compared to the control group for fearful faces in the low attentional load condition. Critically, the stress induced memory bias was accompanied by decoupling between amygdala and DLFPC during encoding, which may represent a mechanism for decreased ability to filter task-irrelevant threatening background information. The current study provides a potential neural account for how stress can produce a negative memory bias for threatening information even if presented outside the focus of attention. Despite of an adaptive advantage for survival, such tendencies may ultimately also lead to generalized fear, a possibility requiring additional investigation.

Tell me what to do: Stress facilitates stimulus-response learning by instruction.

Learning by explicit instruction is a highly efficient way to instantaneously learn new behaviors and to overcome potentially harmful learning by trial-and-error. Despite the importance of instructed learning for education, influences on the efficacy of an instruction are currently unknown. Decades of research, however, showed that stress is a powerful modulator of learning and memory, including the acquisition of stimulus-response (S-R) associations. Moreover, brain areas critical for instructed learning are a major target of hormones and neurotransmitters released during stress. Thus, we investigated here whether acute stress affects instructed S-R learning and whether this effect differs for trial-and-error learning. To this end, healthy participants underwent a stressor (Socially Evaluated Cold Pressor Test) or a control manipulation before learning arbitrary S-R associations. For half of the stimuli, participants were explicitly instructed about the correct association, whereas the remaining associations had to be learned by trial-and-error. As expected, the instruction resulted in better performance and enhanced explicit rule knowledge compared to trial-and-error learning. Stress further boosted the beneficial effect of an explicit instruction on learning performance, while leaving trial-and-error learning unchanged. These beneficial effects of stress were directly correlated with the activity of the autonomic nervous system and the concentration of cortisol. Moreover, acute stress could override the detrimental effect of high trait anxiety levels on instructed S-R learning performance. Our findings indicate that acute stress may facilitate learning from instruction, which may represent a highly efficient way to learn how to act, without the necessity of own experience, that helps to save cognitive resources during a stressful encounter.

Flexible processing of distractor stimuli under stress.

Acute stress is assumed to affect executive processing of stimulus information, although extant studies have yielded heterogeneous findings. The temporal flanker task, in which a target stimulus is preceded by a distractor of varying utility, offers a means of investigating various components involved in the adjustment of information processing and conflict control. Both behavioral and EEG data obtained with this task suggest stronger distractor-related response activation in conditions associated with higher predictivity of the distractor for the upcoming target. In two experiments we investigated distractor-related processing and conflict control after inducing acute stress (Trier Social Stress Test). Although the stressed groups did not differ significantly from unstressed control groups concerning behavioral markers of attentional adjustment (i.e., Proportion Congruent Effect), or event-related sensory components in the EEG (i.e., posterior P1 and N1), the lateralized readiness potential demonstrated reduced activation evoked by (predictive) distractor information under stress. Our results suggest flexible adjustment of attention under stress but hint at decreased usage of nominally irrelevant stimulus information for biasing response selection.

Comparison of two reaction-time-based and one foraging-based behavioral approach-avoidance tasks in relation to interindividual differences and their reliability.

Approaching rewards and avoiding punishments is a fundamental aspect of behavior, yet individuals differ in the extent of these behavioral tendencies. One popular method to assess differences in approach-avoidance tendencies and even modify them, is using behavioral tasks in which spontaneous responses to differently valenced stimuli are assessed (e.g., the visual joystick and the manikin task). Understanding whether these reaction-time-based tasks map onto the same underlying constructs, how they predict interindividual differences in theoretically related constructs and how reliable they are, seems vital to make informed judgements about current findings and future studies. In this preregistered study, 168 participants (81 self-identified men, 87 women) completed emotional face versions of these tasks as well as an alternative, foraging-based paradigm, the approach-avoidance-conflict task, and answered self-report questionnaires regarding anxiety, aggression, depressive symptoms, behavioral inhibition and activation. Importantly, approach-avoidance outcome measures of the two reaction-time-based tasks were unrelated with each other, showed little relation to self-reported interindividual differences and had subpar internal consistencies. In contrast, the approach-avoidance-conflict task was related to behavioral inhibition and aggression, and had good internal consistencies. Our study highlights the need for more research into optimizing behavioral approach-avoidance measures when using task-based approach-avoidance measures to assess interindividual differences.

The effects of hydrocortisone and yohimbine on human behavior in approach-avoidance conflicts.

RATIONALE: Balancing approach of positive and avoidance of negative stimuli is essential when faced with approach-avoidance conflicts, e.g., situations with both positive and negative outcomes. This balance is disturbed in several mental disorders, e.g., excessive avoidance in anxiety disorders, and heightened approach in substance use disorders. Since stress is assumed to impact these disorders' etiology and maintenance, it seems crucial to understand how stress influences behavior in approach-avoidance conflicts. Indeed, some studies suggested altered approach-avoidance behavior under acute stress, but the mechanism underlying these effects is unknown. OBJECTIVES: Investigate how the pharmacological manipulation of major stress mediators (cortisol and noradrenaline) influences task-based approach-avoidance conflict behavior in healthy individuals. METHODS: Ninety-six participants (48 women, 48 men) received either 20mg hydrocortisone, 20mg yohimbine, both, or placebo before performing a task targeting foraging under predation in a fully crossed double-blind between-subject design. Moreover, we investigated effects of gender and endogenous testosterone and estradiol levels on approach-avoidance behavior. RESULTS: While biological stress markers (cortisol concentration, alpha amylase activity) indicated successful pharmacological manipulation, behavior in approach-avoidance conflicts was not affected as expected. Although yohimbine administration affected risky foraging latency under predation, we found no main effect of hydrocortisone or their interaction on behavior. In contrast, we found gender differences for almost all behavioral outcome measures, which might be explained by differences in endogenous testosterone levels. CONCLUSIONS: The investigated major stress mediators were not sufficient to imitate previously shown stress effects on approach-avoidance conflict behavior. We discuss potential reasons for our findings and implications for future research.

How interindividual differences shape approach-avoidance behavior: Relating self-report and diagnostic measures of interindividual differences to behavioral measurements of approach and avoidance.

Responding to stimuli in ambiguous environments is partially governed by approach-avoidance tendencies. Imbalances in these approach-avoidance behaviors are implicated in many mental disorders including anxiety disorders, phobias and substance use disorders. While factors biasing human behavior in approach-avoidance conflicts have been researched in numerous experiments, a much-needed comprehensive overview integrating those findings is missing. Here, we systematically searched the existing literature on individual differences in task-based approach-avoidance behavior and aggregated the current evidence for the effect of self-reported approach/avoidance traits, anxiety and anxiety disorders, specific phobias, depression, aggression, anger and psychopathy, substance use and related disorders, eating disorders and habits, trauma, acute stress and, finally, hormone levels (mainly testosterone, oxytocin). We highlight consistent findings, underrepresented research areas and unexpected results, and detail the amount of controversy between studies. We discuss potential reasons for ambiguous results in some research areas, offer practical advice for future studies and highlight potential variables such as task-related researcher decisions that may influence how interindividual differences and disorders drive automatic approach-avoidance biases in behavioral experiments.

No association between FKBP5 gene methylation and acute and long-term cortisol output.

Prior studies identified DNA methylation (DNAM) changes in a regulatory region within the FK506 binding protein 5 (FKBP5) gene as a crucial mediator of long-term negative health outcomes following early adversity. A critical mechanism underlying this link, in turn, has been suggested to be epigenetically induced dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. The purpose of this study was thus to investigate associations of FKBP5 DNAM with both acute and chronic cortisol output. Two hundred adults with differential exposure to childhood trauma (CT) were underwent a laboratory stressor (Trier Social Stress Test) and provided salivary samples for the analysis of acute cortisol stress responses. In addition, hair cortisol concentrations were determined as a valid measure of integrated long-term cortisol levels. Whole blood samples were drawn for DNAM analyses of FKBP5 intron 7 via bisulfite pyrosequencing. In contrast to most prior work, only healthy participants were included in order to disentangle the effects of trauma exposure per se from those related to mental disorders. First, our findings did not reveal strong evidence for a robust effect of CT on FKBP5 intron 7 DNAM status, even if genetic predisposition (rs1360780 genotype) was taken into account. Second, FKBP5 DNAM levels were found to be unrelated to acute cortisol stress reactivity and long-term cortisol concentration in hair. The failure to demonstrate a significant association between CT and FKBP5 DNAM in an exclusively healthy sample could be interpreted as suggesting that individuals' mental health status may be a critical modulator of previously observed effects.

Cortisol secretion predicts functional macro-scale connectivity of the visual cortex: A data-driven Multivoxel Pattern Analysis (MVPA).

BACKGROUND: Functional connectivity is a fundamental principle of brain organization. Cortisol, the end product of the hypothalamic-pituitary-adrenal axis, is a potent modulator of brain functions. Previous studies investigating the association between cortisol levels on brain connectivity are, however, limited to specifica priori defined brain networks. Such hypothesis-driven approaches only partly capture the full extent of spatial modulatory effects that cortisol exerts on brain connectivity. Consequently, the aim of this study was a data-driven identification of brain regions where connectivity patterns covary significantly with cortisol levels. METHODS: Eighty-eight healthy right-handed individuals participated in a task-independent fMRI-resting-state functional connectivity (rsFC) measurement. The cortisol concentrations in saliva were measured at eight points in time around the resting state measurement. Using a multi-voxel pattern analysis (MVPA), seed regions were identified whose activity covaried strongest with cortisol levels. Seed-to-voxel analyses were then performed to isolate corresponding networks affected by cortisol variation. RESULTS: The MVPA identified three regions in the primary and secondary visual cortex where connectivity patterns were associated with cortisol secretion. Seed-to-voxel analysis revealed large lateral connectivity clusters that mainly correspond to the salience and control network, but also to auditory and pericentral regions. Subsequent dose-response analysis suggests that cortisol levels below ∼10 nmol/L weakly influenced connectivity between the identified regions. DISCUSSION: The results indicate a dose-dependent association between cortisol levels and the rsFC of the visual cortex to several lateral brain regions associated with perception, attention, cognition, salience mapping and motor actions. It is possible that the effects of cortisol on cognitive functions may be (at least partially) mediated by cortisol effects on the underlying sensory processes.

Antioxidant effects of xanthohumol and functional impact on hepatic ischemia-reperfusion injury.

Therapeutic effects of dietary flavonoids have been attributed mainly to their antioxidant capacity. Xanthohumol (1), a prominent flavonoid of the hop plant, Humulus lupulus, was investigated for its antioxidant potential and for its effect on NF-kappaB activation. To examine the biological relevance of 1, a hepatic ischemia/reperfusion model was chosen as a widely accepted model of oxidative stress generation. The impact of 1 on endogenous antioxidant systems, on the NF-kappaB signal transduction pathway as well as on apoptotic parameters, and on hepatic tissue damage was evaluated. Compound 1 markedly decreased the level of reactive oxygen species in vitro. Furthermore, levels of enzymatic and nonenzymatic antioxidants were restored after pretreatment in postischemic hepatic tissue, and lipid peroxidation was attenuated. NF-kappaB activity was reduced in vitro as well as in hepatic tissue after ischemia/reperfusion upon pretreatment with 1. In addition, the phosphorylation of Akt was markedly inhibited. Surprisingly, 1 decreased the expression of the antiapoptotic protein Bcl-X and increased caspase-3 like-activity, a proapoptotic parameter. Moreover, hepatic tissue damage as well as TNF-alpha levels increased in xanthohumol-pretreated liver tissue after ischemia/reperfusion. In summary, xanthohumol did not protect against ischemia/reperfusion injury in rat liver, despite its antioxidant and NF-kappaB inhibitory properties.

Prognostic value of negative dobutamine-stress cardiac magnetic resonance imaging.

BACKGROUND: Assessment of left ventricular wall motion during dobutamine-stress magnetic resonance (DSMR) is well established for the identification of myocardial ischemia. However, the integration of DSMR into the process of clinical decision-making in patients with suspected CAD is not well established. The aim of this study was to assess the value of DSMR used for clinical decision-making and to stratify the prognosis following this strategy. MATERIAL/METHODS: Medical records of 123 consecutive patients suspected of having CAD who underwent high-dose DSMR were reviewed and followed for a median of 23+/-12 months. DSMR results were used for decision-making, for example in favor of catheterization by the referring physician. RESULTS: Thirty-four (27.6%) patients had inducible ischemia, of whom 31 (91.2%) underwent invasive angiography, 25 (80.6%) having stenoses of >50% in a vessel of > or =2 mm in diameter. Fifteen of these patients received vascularization (PCI/CABG); only two events (myocardial infarction) were observed during follow-up in this group. Eighty-nine (72.4%) patients had no inducible ischemia; 21 of them (23.6%) had invasive angiography resulting in 0 (0%) significant findings. In the remaining 68 (76.4%) patients with negative DSMR and who were not catheterized, an annual event rate of 0% was observed. CONCLUSIONS: DSMR can be used for clinical decision-making in patients suspected of having CAD. This strategy results in a high prevalence of CAD in patients referred for invasive angiography due to a positive DSMR and an excellent prognosis in all patients with a negative DSMR.

Stress, aggression, and the balance of approach and avoidance.

Stress is a well-established risk factor for many mental disorders including anxiety disorders or substance abuse. A hallmark of these disorders is an imbalance between behavioral approach and avoidance in situations with approach-avoidance conflicts and unclear outcomes. However, if and how stress affects human behavior in approach-avoidance conflicts is largely unknown. To investigate the effects of stress on approach-avoidance behavior, 80 participants underwent a stress or control manipulation before performing an approach-avoidance conflict task. Stress markedly increased behavioral inhibition when threats were distant and accelerated responses when threats were close; suggesting that stress amplifies the importance of threat distance. However, participants high in trait aggression showed increased approach behavior, particularly when stressed. These findings indicate that stress generally leads to enhanced avoidance, but induces approach in individuals prone to aggression, with important implications for stress-related psychopathologies.

Natural and non-natural prenylated chalcones: synthesis, cytotoxicity and anti-oxidative activity.

A general strategy for the synthesis of 3'-prenylated chalcones was established and a series of prenylated hydroxychalcones, including the hop (Humulus lupulus L.) secondary metabolites xanthohumol (1), desmethylxanthohumol (2), xanthogalenol (3), and 4-methylxanthohumol (4) were synthesized. The influence of the A-ring hydroxylation pattern on the cytotoxic activity of the prenylated chalcones was investigated in a HeLa cell line and revealed that non-natural prenylated chalcones, like 2',3,4',5-tetrahydroxy-6'-methoxy-3'-prenylchalcone (9, IC(50) 3.2+/-0.4microM) as well as the phase 1 metabolite of xanthohumol (1), 3-hydroxyxanthohumol (8, IC(50) 2.5+/-0.5microM), were more active in comparison to 1 (IC(50) 9.4+/-1.4microM). A comparison of the cytotoxic activity of xanthohumol (1) and 3-hydroxyxanthohumol (8) with the non-prenylated analogs helichrysetin (12, IC(50) 5.2+/-0.8) and 3-hydroxyhelichrysetin (13, IC(50) 14.8+/-2.1) showed that the prenyl side chain at C-3' has an influence on the cytotoxicity against HeLa cells only for the dihydroxylated derivative. This offers interesting synthetic possibilities for the development of more potent compounds. The ORAC activity of the synthesized compounds was also investigated and revealed the highest activity for compounds 12, 4'-methylxanthohumol (4), and desmethylxanthohumol (2), with 4.4+/-0.6, 3.8+/-0.4, and 3.8+/-0.5 Trolox equivalents, respectively.

Aroyl hydrazones of 2-phenylindole-3-carbaldehydes as novel antimitotic agents.

Cell cycle arrest of malignant cells is an important option for cancer treatment. In this study, we modified the structure of antimitotic 2-phenylindole-3-carbaldehydes by condensation with hydrazides of various benzoic and pyridine carboxylic acids. The resulting hydrazones inhibited the growth of MDA-MB 231 and MCF-7 breast cancer cells with IC(50) values of 20-30 nM for the most potent derivatives. These 2-phenylindole derivatives also exerted an inhibitory effect on the growth of both proliferating and resting U-373 MG glioblastoma cells. Though the hydrazones exhibited similar structure-activity relationships as the aldehydes, they did not inhibit tubulin polymerization as the aldehydes but were capable of blocking the cell cycle in G(2)/M phase. The cell cycle arrest was accompanied by apoptosis as demonstrated by the activation of caspase-3. Since these 2-phenylindole-based hydrazones display no structural similarity with other antitumor drugs they are interesting candidates for further development.

Synthesis, cytotoxicity, and antioxidative activity of minor prenylated chalcones from Humulus lupulus.

The minor hop ( Humulus lupulus) chalcones 3'-geranylchalconaringenin (3), 5'-prenylxanthohumol (4), flavokawin (5), xanthohumol H (8), xanthohumol C (9), and 1'',2''-dihydroxanthohumol C (10) were synthesized. The non-natural chalcones 3'-geranyl-6'-O-methylchalconaringenin (2), 3'-methylflavokawin (6), and 2'-O-methyl-3'-prenylchalconaringenin (7) were also synthesized. Cytotoxicity was investigated in HeLa cells, and these compounds all had IC 50 values comparable to xanthohumol (8.2-19.2 microM). The ORAC-fluorescein assay revealed potent antioxidative activity for 7 and 8 with 5.2 and 4.8 Trolox equivalents, respectively.

Sexual Responses Are Facilitated by High-Order Contextual Cues in Females but Not in Males.

Sexual responses are thought to be controlled by a brain module called the sexual module. Sexual strategies of males and females vary to a great extent, and sexual responses of males and females may be affected by their sexual strategies. However, the current view of the sexual module is that of a unisex module. This might be questionable since brain modules are defined as evolved cognitive mechanisms to solve adaptive problems which are different for males and females. We hypothesize that the sexual module responds differently in the presence of complex (high-order) contextual cues that are related to gender-dimorphic sexual strategies in males and females. We conducted a priming experiment in which stimuli related to sexual strategies were disentangled from their sexual meaning. Nonsexual priming pictures related to either economic resources or social interactions preceded a sexual-target picture in order to test whether the primes were able to modulate the subjective sexual response to the sexual target. In a control condition, priming pictures without relation to mating preferences but with similar emotional impact were presented. In males, sexual responses were similar in the experimental and control conditions. In females, however, primes related to economic resources or social interactions modulated sexual arousal significantly more than the control primes. Our findings suggest that brain modules dedicated to process the experimental primes were functionally connected with the sexual module in females more than in males, making females' sexual responses more prone to the impact of high-order cultural cues than males' sexual responses. A gender-dimorphic connectivity of the sexual module may be the way in which gender-dimorphic sexual strategies are implemented in the human mind.

Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor.

Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this shift is still unclear, previous evidence in rodents points towards cortisol interacting with the mineralocorticoid receptor (MR) to affect amygdala functioning. The amygdala is in turn assumed to orchestrate the stress-induced shift in memory processing. However, an integrative study testing these mechanisms in humans is lacking. Therefore, we combined functional neuroimaging of a spatial memory task, stress-induction, and administration of an MR-antagonist in a full-factorial, randomized, placebo-controlled between-subjects design in 101 healthy males. We demonstrate that stress-induced increases in cortisol lead to enhanced stimulus-response learning, accompanied by increased amygdala activity and connectivity to the striatum. Importantly, this shift was prevented by an acute administration of the MR-antagonist spironolactone. Our findings support a model in which the MR and the amygdala play an important role in the stress-induced shift towards habit memory systems, revealing a fundamental mechanism of adaptively allocating neural resources that may have implications for stress-related mental disorders.