Embracing the Complexity: Surfacing Problem Situations with Multiple Actors of the Pineapple Value Chain in Uganda

The complexity of local situations in which agricultural value chains are enacted requires a systemic understanding when seeking to improve interlinked livelihoods. Studying the fresh pineapple value chain in Uganda offers an illustrative example. Individually negotiated and context-specific actor relationships, along with their connected activities can be revealed by conceptualizing the chain as a purposeful human activity system. We followed a systems learning approach to elicit value chain actors’ perspectives on factors influencing their activities while surfacing relevant problem situations, resolutions and constraints. Participatory methods, including cognitive mapping, were used to spark dialogue during meetings with only farmers, traders and brokers and also with mixed groups. The results present the multiple natural, technical and social factors identified by value chain actors leading to losses and benefits to their income. System driving and shaping influences included infrastructure, seasonality, perishability and weather conditions. Process-oriented analysis of multi-stakeholder discussions revealed feedback cycles related to fragmentation of the chain. This resulted from and contributed to problematic communication, price fluctuations and challenges in actor relations. For example, actors proposed uniform pricing and debated the implications. Although the systemic perspective brought forward actors’ awareness of potential benefits of improved collaboration and recognition of interdependent activities, it also exposed barriers. Participatory systems learning helped to capture actors’ room of maneuver, and can support processes towards actor-driven change.     

Second-Order Cybernetic Analysis to Re-construct Farmers’ Rationale When Regulating Milk Production

This paper presents an activity and knowledge analysis using second-order cybernetics for analysing human activities in social-ecological systems. We do this with the case of smallholder farmers producing milk in Nakuru County, Kenya. The analysis is based on farmers′ actions and the knowledge behind their actions. Using this approach, we analysed how smallholder farmers regulate milk production and how they influence milk quality. Farmers influence milk quality with their routine and problem-solving management actions. The knowledge behind these actions can be represented as rules. We found that Routine Control Rules that influence milk quality aim to (i) minimize contamination (ii) maintain udder health, and (iii) preserve milk. Problem-Solving Control Rules aim to deal with disturbances associated with (i) market imperfection (ii) microbiological contamination (iii) disease, and (iv) unfavourable milk composition. The approach revealed key restrictions and disturbance factors influencing milk quality in smallholder dairy systems. It also allowed for co-identification of best practices and entry points for contextualized innovations, i.e. innovations that fit into the respective production context. The co-analysis led to changes in farmers’ practices, as it fostered the co-development of milk quality standards to be applied at the community level as preparation for collective marketing activities. When emphasis is placed on finding restrictions and developing innovations, the approach can be further applied to other land-use systems.     

No signature of clear CO2 ice from the 'cryptic' regions in Mars' south seasonal polar cap

The seasonal polar ice caps of Mars are composed mainly of CO2 ice. A region of low (< 30%) albedo has been observed within the south seasonal cap during early to mid-spring. The low temperature of this 'cryptic region' has been attributed to a clear slab of nearly pure CO2 ice, with the low albedo resulting from absorption by the underlying surface. Here we report near-infrared imaging spectroscopy of the south seasonal cap. The deep and broad CO2 absorption bands that are expected in the near-infrared with a thick transparent slab of CO2 ice are not observed. Models of the observed spectra indicate that the low albedo results from extensive dust contamination close to the surface of a CO2 ice layer, which could be linked to atmospheric circulation patterns. The strength of the CO2 absorption increases after mid-spring, so part of the dust is either carried away or buried more deeply in the ice layer during the CO2 ice sublimation process.     

Pathogen stress increases somatic recombination frequency in Arabidopsis

Evolution is based on genetic variability and subsequent phenotypic selection. Mechanisms that modulate the rate of mutation according to environmental cues, and thus control the balance between genetic stability and flexibility, might provide a distinct evolutionary advantage. Stress-induced mutations stimulated by unfavorable environments, and possible mechanisms for their induction, have been described for several organisms, but research in this area has mainly focused on microorganisms. We have analyzed the influence of adverse environmental conditions on the genetic stability of the higher plant Arabidopsis thaliana. Here we show that a biotic stress factor-attack by the oomycete pathogen Peronospora parasitica-can stimulate somatic recombination in Arabidopsis. The same effect was observed when plant pathogen-defense mechanisms were activated by the chemicals 2,6-dichloroisonicotinic acid (INA) or benzothiadiazole (BTH), or by a mutation (cim3). Together with previous studies of recombination induced by abiotic factors, these findings suggest that increased somatic recombination is a general stress response in plants. The increased genetic flexibility might facilitate evolutionary adaptation of plant populations to stressful environments.     

Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment

The stress hormone-regulating hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the causality as well as the treatment of depression. To investigate a possible association between genes regulating the HPA axis and response to antidepressants and susceptibility for depression, we genotyped single-nucleotide polymorphisms in eight of these genes in depressed individuals and matched controls. We found significant associations of response to antidepressants and the recurrence of depressive episodes with single-nucleotide polymorphisms in FKBP5, a glucocorticoid receptor-regulating cochaperone of hsp-90, in two independent samples. These single-nucleotide polymorphisms were also associated with increased intracellular FKBP5 protein expression, which triggers adaptive changes in glucocorticoid receptor and, thereby, HPA-axis regulation. Individuals carrying the associated genotypes had less HPA-axis hyperactivity during the depressive episode. We propose that the FKBP5 variant-dependent alterations in HPA-axis regulation could be related to the faster response to antidepressant drug treatment and the increased recurrence of depressive episodes observed in this subgroup of depressed individuals. These findings support a central role of genes regulating the HPA axis in the causality of depression and the mechanism of action of antidepressant drugs.     

Morning and evening peaks of activity rely on different clock neurons of the Drosophila brain

In Drosophila, a 'clock' situated in the brain controls circadian rhythms of locomotor activity. This clock relies on several groups of neurons that express the Period (PER) protein, including the ventral lateral neurons (LN(v)s), which express the Pigment-dispersing factor (PDF) neuropeptide, and the PDF-negative dorsal lateral neurons (LN(d)s). In normal cycles of day and night, adult flies exhibit morning and evening peaks of activity; however, the contribution of the different clock neurons to the rest-activity pattern remains unknown. Here, we have used targeted expression of PER to restore the clock function of specific subsets of lateral neurons in arrhythmic per(0) mutant flies. We show that PER expression restricted to the LN(v)s only restores the morning activity, whereas expression of PER in both the LN(v)s and LN(d)s also restores the evening activity. This provides the first neuronal bases for 'morning' and 'evening' oscillators in the Drosophila brain. Furthermore, we show that the LN(v)s alone can generate 24 h activity rhythms in constant darkness, indicating that the morning oscillator is sufficient to drive the circadian system.     

Insight into steroid scaffold formation from the structure of human oxidosqualene cyclase

In higher organisms the formation of the steroid scaffold is catalysed exclusively by the membrane-bound oxidosqualene cyclase (OSC; lanosterol synthase). In a highly selective cyclization reaction OSC forms lanosterol with seven chiral centres starting from the linear substrate 2,3-oxidosqualene. Valuable data on the mechanism of the complex cyclization cascade have been collected during the past 50 years using suicide inhibitors, mutagenesis studies and homology modelling. Nevertheless it is still not fully understood how the enzyme catalyses the reaction. Because of the decisive role of OSC in cholesterol biosynthesis it represents a target for the discovery of novel anticholesteraemic drugs that could complement the widely used statins. Here we present two crystal structures of the human membrane protein OSC: the target protein with an inhibitor that showed cholesterol lowering in vivo opens the way for the structure-based design of new OSC inhibitors. The complex with the reaction product lanosterol gives a clear picture of the way in which the enzyme achieves product specificity in this highly exothermic cyclization reaction.     

Colon cancer cell-derived 12(S)-HETE induces the retraction of cancer-associated fibroblast via MLC2, RHO/ROCK and Ca<Superscript>2+</Superscript> signalling

Retraction of mesenchymal stromal cells supports the invasion of colorectal cancer cells (CRC) into the adjacent compartment. CRC-secreted 12(S)-HETE enhances the retraction of cancer-associated fibroblasts (CAFs) and therefore, 12(S)-HETE may enforce invasivity of CRC. Understanding the mechanisms of metastatic CRC is crucial for successful intervention. Therefore, we studied pro-invasive contributions of stromal cells in physiologically relevant three-dimensional in vitro assays consisting of CRC spheroids, CAFs, extracellular matrix and endothelial cells, as well as in reductionist models. In order to elucidate how CAFs support CRC invasion, tumour spheroid-induced CAF retraction and free intracellular Ca²⁺ levels were measured and pharmacological- or siRNA-based inhibition of selected signalling cascades was performed. CRC spheroids caused the retraction of CAFs, generating entry gates in the adjacent surrogate stroma. The responsible trigger factor 12(S)-HETE provoked a signal, which was transduced by PLC, IP3, free intracellular Ca²⁺, Ca²⁺-calmodulin-kinase-II, RHO/ROCK and MYLK which led to the activation of myosin light chain 2, and subsequent CAF mobility. RHO activity was observed downstream as well as upstream of Ca²⁺ release. Thus, Ca²⁺ signalling served as central signal amplifier. Treatment with the FDA-approved drugs carbamazepine, cinnarizine, nifedipine and bepridil HCl, which reportedly interfere with cellular calcium availability, inhibited CAF-retraction. The elucidation of signalling pathways and identification of approved inhibitory drugs warrant development of intervention strategies targeting tumour–stroma interaction.