Drivers and spatio-temporal extent of hyporheic patch variation: implications for sampling

The hyporheic zone in stream ecosystems is a heterogeneous key habitat for species across many taxa. Consequently, it attracts high attention among freshwater scientists, but generally applicable guidelines on sampling strategies are lacking. Thus, the objective of this study was to develop and validate such sampling guidelines. Applying geostatistical analysis, we quantified the spatio-temporal variability of parameters, which characterize the physico-chemical substratum conditions in the hyporheic zone. We investigated eight stream reaches in six small streams that are typical for the majority of temperate areas. Data was collected on two occasions in six stream reaches (development data), and once in two additional reaches, after one year (validation data). In this study, the term spatial variability refers to patch contrast (patch to patch variance) and patch size (spatial extent of a patch). Patch contrast of hyporheic parameters (specific conductance, pH and dissolved oxygen) increased with macrophyte cover (r² = 0.95, p<0.001), while patch size of hyporheic parameters decreased from 6 to 2 m with increasing sinuosity of the stream course (r² = 0.91, p<0.001), irrespective of the time of year. Since the spatial variability of hyporheic parameters varied between stream reaches, our results suggest that sampling design should be adapted to suit specific stream reaches. The distance between sampling sites should be inversely related to the sinuosity, while the number of samples should be related to macrophyte cover.     

Investigating Neural Efficiency in the Visuo-Spatial Domain: An fmri Study

The neural efficiency hypothesis postulates an inverse relationship between intelligence and brain activation. Previous research suggests that gender and task modality represent two important moderators of the neural efficiency phenomenon. Since most of the existing studies on neural efficiency have used ERD in the EEG as a measure of brain activation, the central aim of this study was a more detailed analysis of this phenomenon by means of functional MRI. A sample of 20 males and 20 females, who had been screened for their visuo-spatial intelligence, was confronted with a mental rotation task employing an event-related approach. Results suggest that less intelligent individuals show a stronger deactivation of parts of the default mode network, as compared to more intelligent people. Furthermore, we found evidence of an interaction between task difficulty, intelligence and gender, indicating that more intelligent females show an increase in brain activation with an increase in task difficulty. These findings may contribute to a better understanding of the neural efficiency hypothesis, and possibly also of gender differences in the visuo-spatial domain.     

Smooth Pursuit and Visual Occlusion: Active Inference and Oculomotor Control in Schizophrenia

This paper introduces a model of oculomotor control during the smooth pursuit of occluded visual targets. This model is based upon active inference, in which subjects try to minimise their (proprioceptive) prediction error based upon posterior beliefs about the hidden causes of their (exteroceptive) sensory input. Our model appeals to a single principle – the minimisation of variational free energy – to provide Bayes optimal solutions to the smooth pursuit problem. However, it tries to accommodate the cardinal features of smooth pursuit of partially occluded targets that have been observed empirically in normal subjects and schizophrenia. Specifically, we account for the ability of normal subjects to anticipate periodic target trajectories and emit pre-emptive smooth pursuit eye movements – prior to the emergence of a target from behind an occluder. Furthermore, we show that a single deficit in the postsynaptic gain of prediction error units (encoding the precision of posterior beliefs) can account for several features of smooth pursuit in schizophrenia: namely, a reduction in motor gain and anticipatory eye movements during visual occlusion, a paradoxical improvement in tracking unpredicted deviations from target trajectories and a failure to recognise and exploit regularities in the periodic motion of visual targets. This model will form the basis of subsequent (dynamic causal) models of empirical eye tracking measurements, which we hope to validate, using psychopharmacology and studies of schizophrenia.     

Mapping the Laminin Receptor Binding Domains of Neisseria meningitidis PorA and Haemophilus influenzae OmpP2

Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae are major bacterial agents of meningitis. They each bind the 37/67-kDa laminin receptor (LamR) via the surface protein adhesins: meningococcal PilQ and PorA, H. influenzae OmpP2 and pneumococcal CbpA. We have previously reported that a surface-exposed loop of the R2 domain of CbpA mediates LamR-binding. Here we have identified the LamR-binding regions of PorA and OmpP2. Using truncated recombinant proteins we show that binding is dependent on amino acids 171–240 and 91–99 of PorA and OmpP2, respectively, which are predicted to localize to the fourth and second surface-exposed loops, respectively, of these proteins. Synthetic peptides corresponding to the loops bound LamR and could block LamR-binding to bacterial ligands in a dose dependant manner. Meningococci expressing PorA lacking the apex of loop 4 and H. influenzae expressing OmpP2 lacking the apex of loop 2 showed significantly reduced LamR binding. Since both loops are hyper-variable, our data may suggest a molecular basis for the range of LamR-binding capabilities previously reported among different meningococcal and H. influenzae strains.     

Structures of Human DPP7 Reveal the Molecular Basis of Specific Inhibition and the Architectural Diversity of Proline-Specific Peptidases

Proline-specific dipeptidyl peptidases (DPPs) are emerging targets for drug development. DPP4 inhibitors are approved in many countries, and other dipeptidyl peptidases are often referred to as DPP4 activity- and/or structure-homologues (DASH). Members of the DASH family have overlapping substrate specificities, and, even though they share low sequence identity, therapeutic or clinical cross-reactivity is a concern. Here, we report the structure of human DPP7 and its complex with a selective inhibitor Dab-Pip (L-2,4-diaminobutyryl-piperidinamide) and compare it with that of DPP4. Both enzymes share a common catalytic domain (α/β-hydrolase). The catalytic pocket is located in the interior of DPP7, deep inside the cleft between the two domains. Substrates might access the active site via a narrow tunnel. The DPP7 catalytic triad is completely conserved and comprises Ser162, Asp418 and His443 (corresponding to Ser630, Asp708 and His740 in DPP4), while other residues lining the catalytic pockets differ considerably. The "specificity domains" are structurally also completely different exhibiting a β-propeller fold in DPP4 compared to a rare, completely helical fold in DPP7. Comparing the structures of DPP7 and DPP4 allows the design of specific inhibitors and thus the development of less cross-reactive drugs. Furthermore, the reported DPP7 structures shed some light onto the evolutionary relationship of prolyl-specific peptidases through the analysis of the architectural organization of their domains.     

Dissociated neural processing for decisions in managers and non-managers

Functional neuroimaging studies of decision-making so far mainly focused on decisions under uncertainty or negotiation with other persons. Dual process theory assumes that, in such situations, decision making relies on either a rapid intuitive, automated or a slower rational processing system. However, it still remains elusive how personality factors or professional requirements might modulate the decision process and the underlying neural mechanisms. Since decision making is a key task of managers, we hypothesized that managers, facing higher pressure for frequent and rapid decisions than non-managers, prefer the heuristic, automated decision strategy in contrast to non-managers. Such different strategies may, in turn, rely on different neural systems. We tested managers and non-managers in a functional magnetic resonance imaging study using a forced-choice paradigm on word-pairs. Managers showed subcortical activation in the head of the caudate nucleus, and reduced hemodynamic response within the cortex. In contrast, non-managers revealed the opposite pattern. With the head of the caudate nucleus being an initiating component for process automation, these results supported the initial hypothesis, hinting at automation during decisions in managers. More generally, the findings reveal how different professional requirements might modulate cognitive decision processing.     

A High-Throughput Forward Genetic Screen Identifies Genes Required for Virulence of Pseudomonas syringae pv. maculicola ES4326 on Arabidopsis

Successful pathogenesis requires a number of coordinated processes whose genetic bases remain to be fully characterized. We utilized a high-throughput, liquid media-based assay to screen transposon disruptants of the phytopathogen Pseudomonas syringae pv. maculicola ES4326 to identify genes required for virulence on Arabidopsis. Many genes identified through this screen were involved in processes such as type III secretion, periplasmic glucan biosynthesis, flagellar motility, and amino acid biosynthesis. A small set of genes did not fall into any of these functional groups, and their disruption resulted in context-specific effects on in planta bacterial growth.     

C4 abundance in an Inner Mongolia grassland system is driven by temperature–moisture interaction,not grazing pressure

Global warming and CO₂ rise is expected to change the balance of C3 and C4 plants in grassland vegetation, but disturbance, including grazing, could also affect C3/C4 community structure. We used a six-year (2005–2010) grazing experiment to test the prediction that the relative abundance of C4 plants (P_C4) in the semi-arid grassland of Inner Mongolia is related to growing-period temperature and disturbance by grazing. Paddocks were stocked with sheep at six rates (0.375–2.25 sheep ha^?1 a^?1) between June and September. P_C4 was estimated from the relative ¹³C/¹²C composition (δ¹³C) of wool grown during the grazing period of each year and a two-member mixing model of the δ¹³C of the C3 and C4 communities in the paddocks. Stocking rate had a slight effect (<0.5‰) on the δ¹³C of the C3 and the C4 end-members. Annual average P_C4 varied between 5% and 24%. Stocking rate had no significant effect on P_C4 but the growing-season temperature had a large effect, and P_C4 increased with temperature. Importantly, the growing season shifted between years due to changing seasonal distribution of rainfall and soil moisture availability from winter precipitation causing large variation in temperature of the effective growing season. Changes in temperature and in amount and seasonal distribution of rainfall as a consequence of inter-annual fluctuations and long-term change can thus have a large impact on the C4 abundance and its spatial pattern.     

Fluoxetine induces vasodilatation of cerebral arterioles by co‐modulating NO/muscarinic signalling

Ischaemic stroke patients treated with Selective Serotonin Reuptake Inhibitors (SSRI) show improved motor, cognitive and executive functions, but the underlying mechanism(s) are incompletely understood. Here, we report that cerebral arterioles in the rat brain superfused with therapeutically effective doses of the SSRI fluoxetine showed consistent, dose‐dependent vasodilatation (by 1.2 to 1.6‐fold), suppressible by muscarinic and nitric oxide synthase (NOS) antagonists [atropine, NG‐nitro‐l ‐arginine methyl ester (l ‐NAME)] but resistant to nicotinic and serotoninergic antagonists (mecamylamine, methylsergide). Fluoxetine administered 10–30 min. following experimental vascular photo‐thrombosis increased arterial diameter (1.3–1.6), inducing partial, but lasting reperfusion of the ischaemic brain. In brain endothelial b.End.3 cells, fluoxetine induced rapid muscarinic receptor‐dependent increases in intracellular [Ca²⁺] and promoted albumin‐ and eNOS‐dependent nitric oxide (NO) production and HSP90 interaction. In vitro, fluoxetine suppressed recombinant human acetylcholinesterase (rhAChE) activity only in the presence of albumin. That fluoxetine induces vasodilatation of cerebral arterioles suggests co‐promotion of endothelial muscarinic and nitric oxide signalling, facilitated by albumin‐dependent inhibition of serum AChE.