Agriculture rivals biomes in predicting global species richness

Species–area relationships (SARs) provide an avenue to model patterns of species richness and have recently been shown to vary substantially across regions of different climate, vegetation, and land cover. Given that a large proportion of the globe has been converted to agriculture, and considering the large variety in agricultural management practices, a key question is whether global SARs vary across gradients of agricultural intensity. We developed SARs for mammals that account for geographic variation in biomes, land cover and a range of land‐use intensity indicators representing inputs (e.g. fertilizer, irrigation), outputs (e.g. yields) and system‐level measures of intensity (e.g. human appropriation of net primary productivity – HANPP). We systematically compared the resulting SARs in terms of their predictive ability. Our global SAR with a universal slope was significantly improved by the inclusion of any one of the three variable types: biomes, land cover, and land‐use intensity. The latter, in the form of human appropriation of net primary productivity (HANPP), performed as well as biomes and land‐cover in predicting species richness. Other land‐use intensity indicators had a lower predictive ability. Our main finding that land‐use intensity performs as well as biomes and land cover in predicting species richness emphasizes that human factors are on a par with environmental factors in predicting global patterns of biodiversity. While our broad‐scale study cannot establish causality, human activity is known to drive species richness at a local scale, and our findings suggest that this may hold true at a global scale. The ability of land‐use intensity to explain variation in SARs at a global scale had not previously been assessed. Our study suggests that the inclusion of land‐use intensity in SAR models allows us to better predict and understand species richness patterns.     

Functional gene polymorphisms in the serotonin system and traumatic life events modulate the neural basis of fear acquisition and extinction

Fear acquisition and extinction are crucial mechanisms in the etiology and maintenance of anxiety disorders. Moreover, they might play a pivotal role in conveying the influence of genetic and environmental factors on the development of a (more or less) stronger proneness for, or resilience against psychopathology. There are only few insights in the neurobiology of genetically and environmentally based individual differences in fear learning and extinction. In this functional magnetic resonance imaging study, 74 healthy subjects were investigated. These were invited according to 5-HTTLPR/rs25531 (S+ vs. L(A)L(A); triallelic classification) and TPH2 (G(-703)T) (T+ vs. T-) genotype. The aim was to investigate the influence of genetic factors and traumatic life events on skin conductance responses (SCRs) and neural responses (amygdala, insula, dorsal anterior cingulate cortex (dACC) and ventromedial prefrontal cortex (vmPFC)) during acquisition and extinction learning in a differential fear conditioning paradigm. Fear acquisition was characterized by stronger late conditioned and unconditioned responses in the right insula in 5-HTTLPR S-allele carriers. During extinction traumatic life events were associated with reduced amygdala activation in S-allele carriers vs. non-carriers. Beyond that, T-allele carriers of the TPH2 (G(-703)T) polymorphism with a higher number of traumatic life events showed enhanced responsiveness in the amygdala during acquisition and in the vmPFC during extinction learning compared with non-carriers. Finally, a combined effect of the two polymorphisms with higher responses in S- and T-allele carriers was found in the dACC during extinction. The results indicate an increased expression of conditioned, but also unconditioned fear responses in the insula in 5-HTTLPR S-allele carriers. A combined effect of the two polymorphisms on dACC activation during extinction might be associated with prolonged fear expression. Gene-by-environment interactions in amygdala and vmPFC activation may reflect a neural endophenotype translating genetic and adverse environmental influences into vulnerability for or resilience against developing affective psychopathology.     

Mechanography in children: pediatric references in postural control

Objective:To establish pediatric age- and sex-specific references for measuring postural control with a mechanography plate in a single centre, prospective, normative data study.Methods:739 children and adolescents (396 male/343 female) aged 4 to 17 years were studied. Each participant completed the following test sequence three times: Romberg, semi-tandem, tandem, each with eyes open and closed, and a one-leg stand with eyes open, and a single two-legged jump. Normal ranges were determined based on percentile calculations using the LMS method. Results from the two-legged jump were compared to a reference population the single two-legged jump (s2LJ) assessment in 2013.Results:38 different equilibrium parameters calculated were analysed. Of all parameters Path Length, vCoFmean, Equilibrium Score and Sway Angle showed a low variation within the same age group but high dependency on age and were thus chosen for automated balance assessment.Conclusion:Standard values of postural control in healthy children derived from automated balance testing using a mechanography plate were successfully acquired and a subset of parameters for automated balance assessment identified.     

Bipolar‐associated miR‐499‐5p controls neuroplasticity by downregulating the Cav1.2 subunit CACNB2

Bipolar disorder (BD) is a chronic mood disorder characterized by manic and depressive episodes. Dysregulation of neuroplasticity and calcium homeostasis are frequently observed in BD patients, but the underlying molecular mechanisms are largely unknown. Here, we show that miR‐499‐5p regulates dendritogenesis and cognitive function by downregulating the BD risk gene CACNB2. miR‐499‐5p expression is increased in peripheral blood of BD patients, as well as in the hippocampus of rats which underwent juvenile social isolation. In rat hippocampal neurons, miR‐499‐5p impairs dendritogenesis and reduces surface expression and activity of the L‐type calcium channel Cav1.2. We further identified CACNB2, which encodes a regulatory β‐subunit of Cav1.2, as a direct functional target of miR‐499‐5p in neurons. miR‐499‐5p overexpression in the hippocampus in vivo induces short‐term memory impairments selectively in rats haploinsufficient for the Cav1.2 pore forming subunit Cacna1c. In humans, miR‐499‐5p expression is negatively associated with gray matter volumes of the left superior temporal gyrus, a region implicated in auditory and emotional processing. We propose that stress‐induced miR‐499‐5p overexpression contributes to dendritic impairments, deregulated calcium homeostasis, and neurocognitive dysfunction in BD.     

LPS inhibits caspase 3-dependent apoptosis in RAW264.7 macrophages induced by the AMPK activator AICAR

AMP-activated kinase is a cellular energy sensor which is activated in stages of increased ATP consumption. Its activation has been associated with a number of beneficial effects such as decreasing inflammatory processes and the disease progress of diabetes and obesity, respectively. Furthermore, AMPK activation has been linked with induction of cell cycle arrest and apoptosis in cancer and vascular cells, indicating that it might have a therapeutic impact for the treatment of cancer and atherosclerosis. However, the impact of AMPK on the proliferation of macrophages, which also play a key role in the formation of atherosclerotic plaques and in inflammatory processes, has not been focused so far. We have assessed the influence of AICAR- and metformin-induced AMPK activation on cell viability of macrophages with and without inflammatory stimulation, respectively. In cells without inflammatory stimulation, we found a strong induction of caspase 3-dependent apoptosis associated with decreased mTOR levels and increased expression of p21. Interestingly, these effects could be inhibited by co-stimulation with bacterial lipopolysaccharide (LPS) but not by other proinflammatory cytokines suggesting that AICAR induces apoptosis via AMPK in a TLR4-pathway dependent manner.     

Electron transfer studies on Cu(II) complexes bearing phenoxy-pincer ligands

Oxido-pincer ligands with phenolate-groups [2,6-bis(2-methoxyphenyl)pyridine (LOMe₂), 2,6-bis(2-hydroxyphenyl)-pyridine (LOH₂), 2,6-bis-(2,4-dimethoxyphenyl)-pyridine (LOMe₄)] coordinate to Cu^II forming binuclear complexes which can be easily and reliably converted into mononuclear species. Their physical properties were analysed using EPR, optical spectroscopy and (spectro-)electrochemical methods. The results were compared to those of related Ni^II complexes and discussed in view of Cu-containing metalloenzymes. Due to the ligands flexibility the Cu^II/Cu^I redox couple exhibits high reversibility, while the ligand-centred oxidation leads to highly reactive phenoxy radicals. Reduction of the LOH₂ complex leads to sequential deprotonation. The ligand LOMe₄ and the derived complexes show blue luminescence, which can be rationalised from its molecular structure (analysed by XRD).     

High-content assays for evaluating cellular and hepatic diacylglycerol acyltransferase activity

Acyl-CoA:diacylglycerol acyltransferase (DGAT) catalyzes the terminal step in triglyceride (TG) synthesis using diacylglycerol (DAG) and fatty acyl-CoA as substrates. In the liver, the production of VLDL permits the delivery of hydrophobic TG from the liver to peripheral tissues for energy metabolism. We describe here a novel high-content, high-throughput LC/MS/MS-based cellular assay for determining DGAT activity. We treated endogenous DGAT-expressing cells with stable isotope-labeled [¹³C₁₈]oleic acid. The [¹³C₁₈]oleoyl-incorporated TG and DAG lipid species were profiled. The TG synthesis pathway assay was optimized to a one-step extraction, followed by LC/MS/MS quantification. Further, we report a novel LC/MS/MS method for tracing hepatic TG synthesis and VLDL-TG secretion in vivo by administering [¹³C₁₈]oleic acid to rats. The [¹³C₁₈]oleic acid-incorporated VLDL-TG was detected after one-step extraction without conventional separation of TG and recovery by derivatizing [¹³C₁₈]oleic acid for detection. Using potent and selective DGAT1 inhibitors as pharmacological tools, we measured changes in [¹³C₁₈]oleoyl-incorporated TG and DAG and demonstrated that DGAT1 inhibition significantly reduced [¹³C₁₈]oleoyl-incorporated VLDL-TG. This DGAT1-selective assay will enable researchers to discern differences between the roles of DGAT1 and DGAT2 in TG synthesis in vitro and in vivo.