Incident light orientation lets C4 monocotyledonous leaves make light work differently

Photosynthesis is an important driver of ecosystem sustainability in the face of climate change. Monocotyledonous crop species with C4 photosynthesis such as maize (Zea mays L; corn) and sugar cane are crucial for future food security and biofuel crop requirements, while C4 pasture grasses such as Paspalum are central to natural ecosystems. The global demand for corn will exceed that for wheat and rice by 2020, making it the world's most important crop. Light-driven photosynthesis supports plant biomass production, but plants have also evolved safety valve mechanisms that attenuate the absorption of potentially lethal levels of excess light. The array of survival responses that enables leaves to evade photoinhibition is complex and involves chloroplast and leaf movement as well as the molecular rearrangements that facilitate thermal energy dissipation. Here we report a novel morphological mechanism that allows C4 monocotyledonous leaves to regulate photosynthesis independently on each surface with respect to incident light allowing better adaptation to water deficits and light stress. We show that under abaxial illumination as occurs when monocotyledonous leaves curl in response to water stress the stomata close and photosynthetic metabolism shuts down on the adaxial surface of C4 leaves but these parameters increase in function to the abaxial surface. We discuss how this regulation confers a survival advantage to the C4 relative to C3 leaves which are unable to regulate their dorso-ventral functions in relation to light

Efficient preparation of TMSCCl2Br and its use in dichlorocyclopropanation of electron deficient alkenes

The reaction of excess TMSCl and LiCCl2Br at low temperature is a technically simple high yield route to TMSCCl2Br. The latter is a stable source of the dichlorobromomethide carbanion, which undergoes 1,4-addition with cyclic nitroalkenes and (E)-fumarates leading to dichlorocyclopropanes after bromide explusion. For nitrostyrenes the reaction arrests at the 1,4-addition product. Low temperature NMR studies and DFT calculations suggest the formation of an ‘ate’ species [(nitronate)SiFMe3]- which, upon boil off of TMSF at 10 - 20 °C, yields the cyclopropane. DFT calculations also support the experimental differences between fluoride and acetate as promotors

Single copy/knock-in models of ALS SOD1 in C. elegans suggest loss and gain of function have different contributions to cholinergic and glutamatergic neurodegeneration

Mutations in Cu/Zn superoxide dismutase 1 (SOD1) lead to Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease that disproportionately affects glutamatergic and cholinergic motor neurons. Previous work with SOD1 overexpression models supports a role for SOD1 toxic gain of function in ALS pathogenesis. However, the impact of SOD1 loss of function in ALS cannot be directly examined in overexpression models. In addition, overexpression may obscure the contribution of SOD1 loss of function in the degeneration of different neuronal populations. Here, we report the first single-copy, ALS knock-in models in C. elegans generated by transposon- or CRISPR/Cas9- mediated genome editing of the endogenous sod-1 gene. Introduction of ALS patient amino acid changes A4V, H71Y, L84V, G85R or G93A into the C. elegans sod-1 gene yielded single-copy/knock-in ALS SOD1 models. These differ from previously reported overexpression models in multiple assays. In single-copy/knock-in models, we observed differential impact of sod-1 ALS alleles on glutamatergic and cholinergic neurodegeneration. A4V, H71Y, G85R, and G93A animals showed increased SOD1 protein accumulation and oxidative stress induced degeneration, consistent with a toxic gain of function in cholinergic motor neurons. By contrast, H71Y, L84V, and G85R lead to glutamatergic neuron degeneration due to sod-1 loss of function after oxidative stress. However, dopaminergic and serotonergic neuronal populations were spared in single-copy ALS models, suggesting a neuronal-subtype specificity previously not reported in invertebrate ALS SOD1 models. Combined, these results suggest that knock-in models may reproduce the neurotransmitter-type specificity of ALS and that both SOD1 loss and gain of toxic function differentially contribute to ALS pathogenesis in different neuronal populations.Peer reviewe

Cooperative Intersection Crossing Over 5G

IEEE Autonomous driving is a safety critical application of sensing and decision-making technologies. Communication technologies extend the awareness capabilities of vehicles, beyond what is achievable with the on-board systems only. Nonetheless, issues typically related to wireless networking must be taken into account when designing safe and reliable autonomous systems. The aim of this work is to present a control algorithm and a communication paradigm over 5G networks for negotiating traffic junctions in urban areas. The proposed control framework has been shown to converge in a finite time and the supporting communication software has been designed with the objective of minimizing communication delays. At the same time, the underlying network guarantees reliability of the communication. The proposed framework has been successfully deployed and tested, in partnership with Ericsson AB, at the AstaZero proving ground in Goteborg, Sweden. In our experiments, three heterogeneous autonomous vehicles successfully drove through a 4-way intersection of 235 square meters in an urban scenario

Microbial players and processes involved in phytoplankton bloom utilization in the water column of a fast-flowing, river-dominated estuary

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in MicrobiologyOpen 6 (2017): e467, doi:10.1002/mbo3.467.Fueled by seasonal phytoplankton blooms, the Columbia River estuary is a natural bioreactor for organic matter transformations. Prior metagenome analyses indicated high abundances of diverse Bacteroidetes taxa in estuarine samples containing phytoplankton. To examine the hypothesis that Bacteroidetes taxa have important roles in phytoplankton turnover, we further analyzed metagenomes from water collected along a salinity gradient at 0, 5, 15, 25, and 33 PSU during bloom events. Size fractions were obtained by using a 3-μm prefilter and 0.2-μm collection filter. Although this approach targeted bacteria by removing comparatively large eukaryotic cells, the metagenome from the ES-5 sample (5 PSU) nevertheless contained an abundance of diatom DNA. Biogeochemical measurements and prior studies indicated that this finding resulted from the leakage of cellular material due to freshwater diatom lysis at low salinity. Relative to the other metagenomes, the bacterial fraction of ES-5 was dramatically depleted of genes annotated as Bacteroidetes and lysogenic bacteriophages, but was overrepresented in DNA of protists and Myxococcales bacterivores. We suggest the following equally plausible scenarios for the microbial response to phytoplankton lysis: (1) Bacteroidetes depletion in the free-living fraction may at least in part be caused by their attachment to fluvial diatoms as the latter are lysed upon contact with low-salinity estuarine waters; (2) diatom particle colonization is likely followed by rapid bacterial growth and lytic phage infection, resulting in depletion of lysogenic bacteriophages and host bacteria; and (3) the subsequent availability of labile organic matter attracted both grazers and predators to feed in this estuarine biogeochemical “hotspot,” which may have additionally depleted Bacteroidetes populations. These results represent the first detailed molecular analysis of the microbial response to phytoplankton lysis at the freshwater–brackish water interface in the fast-flowing Columbia River estuary.National Science Foundation Grant Numbers: OCE 0424602, MCB 064446

Premature T cell aging in major depression: A double hit by the state of disease and cytomegalovirus infection

Childhood trauma; Major depressive disorder; T cytotoxic cellTrauma infantil; Trastorn depressiu major; cèl·lula T citotòxicaTrauma infantil; Trastorno depresivo mayor; célula T citotóxicaIntroduction Previous research indicates that premature T cell senescence is a characteristic of major depressive disorder (MDD). However, known senescence inducing factors like cytomegalovirus (CMV) infection or, probably, childhood adversity (CA) have not been taken into consideration so far. Objective Differentiation and senescent characteristics of T cells of MDD patients were investigated in relation to healthy controls (HC), taking the CMV seropositivity and CA into account. Methods 127 MDD and 113 HC of the EU-MOODSTRATIFICATION cohort were analyzed. Fluorescence activated cell sorting (FACS) analysis was performed to determine B, NK, and T cell frequencies. In a second FACS analysis, naïve, effector memory (Tem), central memory (Tcm), effector memory cells re-expressing RA (TEMRA), as well as CD28+ and CD27+ memory populations, were determined of the CD4+ and CD8+ T cell populations in a subsample (N = 35 MDD and N = 36 HC). CMV-antibody state was measured by IgG ELISA and CA by the Childhood Trauma Questionnaire. Results We detected a CMV-antibody positivity in 40% of MDD patients (35% HC, n. s.) with seropositive MDD cases showing a higher total childhood trauma score. Second, a higher inflation of memory CD4+ T helper cells in CMV seronegative patients as compared to seronegative HC and reduced numbers of naïve CD4+ T helper cells in CMV seropositive patients (not in CMV seropositive HC) were found. Third, a higher inflation of memory CD8+ T cytotoxic cells in CMV seropositive cases as compared to CMV seropositive HC, particularly of the TEMRA cells, became apparent. Higher percentages of CD4+ TEMRA and late stage CD27−CD28− TEMRA cells were similar in both HC and MDD with CMV seropositivity. Overall, apportioning of T cell subpopulations did not differ between CA positive vs negative cases. Conclusions MDD patients show several signs of a CMV independent “MDD specific” premature T cell aging, such as a CMV independent increase in CD4+ T memory cells and a latent naïve CD4 T-cell reduction and a latent CD8+ T-cell increase. However, these two latent T cell senescence abnormalities only become evident with CMV infection (double hit).This work was supported by the European Commission: EU 7th Framework program (grant number EU-FP7-CP-IP-2008-222963) and Horizon 2020 (grant number H2020-SC1-2016-2017/H2020-SC1-2017-Two-Stage-RTD) grants were received by HAD, Erasmus Medical Center Rotterdam. The funding source had no role in the study design, the data collection, the analysis and interpretation of data, the manuscript writing, and in the decision to submit the article for publication

Efficacy of Sertraline Plus Placebo or Add-On Celecoxib in Major Depressive Disorder: Macrophage Migration Inhibitory Factor as a Promising Biomarker for Remission After Sertraline-Results From a Randomized Controlled Clinical Trial

Trastorno depresivo mayor; Tratamiento antiinflamatorio; CitocinaTrastorn depressiu major; Tractament antiinflamatori; CitocinaMajor depressive disorder; Anti-inflammatory treatment; CytokineIntroduction: Previous research delivers strong indications that inflammatory activation leads to treatment resistance in a subgroup of patients with Major Depressive Disorder (MDD). Thus, tailored interventions are needed. The present study aimed to find potential biomarkers that may enable patients to be stratified according to immune activation. Methods: A phase IIa randomized placebo-controlled trial was performed to assess levels of inflammatory compounds in responders/remitters and non-responders/non-remitters to sertraline plus celecoxib (n = 20) and sertraline plus placebo (n = 23). Levels of macrophage migration inhibitory factor, neopterin, and tumor necrosis factor alpha were determined by enzyme-linked immunosorbent assay; response and remission were measured by reduction of the Montgomery Åsberg Depression Rating Scale score. Results: Both treatment groups showed a significant decline in depression symptoms, but no difference was found between groups. A clear pattern emerged only for macrophage migration inhibitory factor: placebo remitters showed significantly lower baseline levels than non-remitters (a similar trend was seen in responders and non-responders) while celecoxib responders showed a trend for higher baseline levels than non-responders. Conclusion: Small subsample sizes are a notable limitation, wherefore results are preliminary. However, the present study provides novel insights by suggesting macrophage migration inhibitory factor as a promising biomarker for treatment choice.This present work was funded by the EU 7th Framework program (grant number EU-FP7-CP-IP-2008-222963/EU-FP7-PEOPLE-2009-IAPP-MarieCurie-286334) and Horizon 2020 (grant number H2020-SC1-2016-2017/H2020-SC1-2017-Two-Stage-RTD). Further, part of this work was supported by the foundation Immunität und Seele. The funders had no role in the study design, data collection and analysis, or decision to publish

Low-grade inflammation as a predictor of antidepressant and anti- inflammatory therapy response in MDD patients: a systematic review of the literature in combination with an analysis of experimental data collected in the EU-MOODINFLAME consortium

Terapia antiinflamatoria; Terapia antidepresiva; InflamaciónAnti-inflammatory therapy; Antidepressant therapy; InflammationTeràpia antiinflamatòria; Teràpia antidepressiva; InflamacióLow-grade inflammation plays a role not only in the pathogenesis of major depressive disorder (MDD) but probably also in the poor responsiveness to regular antidepressants. There are also indications that anti-inflammatory agents improve the outcomes of antidepressants. Aim: To study whether the presence of low-grade inflammation predicts the outcome of antidepressants, anti-inflammatory agents, or combinations thereof. Methods: We carried out a systematic review of the literature on the prediction capability of the serum levels of inflammatory compounds and/or the inflammatory state of circulating leukocytes for the outcome of antidepressant/anti-inflammatory treatment in MDD. We compared outcomes of the review with original data (collected in two limited trials carried out in the EU project MOODINFLAME) on the prediction capability of the inflammatory state of monocytes (as measured by inflammatory gene expression) for the outcome of venlafaxine, imipramine, or sertraline treatment, the latter with and without celecoxib added. Results: Collectively, the literature and original data showed that: 1) raised serum levels of pro-inflammatory compounds (in particular of CRP/IL-6) characterize an inflammatory form of MDD with poor responsiveness to predominately serotonergic agents, but a better responsiveness to antidepressant regimens with a) (add-on) noradrenergic, dopaminergic, or glutamatergic action or b) (add-on) anti-inflammatory agents such as infliximab, minocycline, or eicosapentaenoic acid, showing—next to anti-inflammatory—dopaminergic or lipid corrective action; 2) these successful anti-inflammatory (add-on) agents, when used in patients with low serum levels of CRP/IL-6, decreased response rates in comparison to placebo. Add-on aspirin, in contrast, improved responsiveness in such “non-inflammatory” patients; 3) patients with increased inflammatory gene expression in circulating leukocytes had a poor responsiveness to serotonergic/noradrenergic agents. Conclusions: The presence of inflammation in patients with MDD heralds a poor outcome of first-line antidepressant therapies. Immediate step-ups to dopaminergic or glutamatergic regimens or to (add-on) anti-inflammatory agents are most likely indicated. However, at present, insufficient data exist to design protocols with reliable inflammation parameter cutoff points to guide such therapies, the more since detrimental outcomes are possible of anti-inflammatory agents in “non-inflamed” patients.This study was financially supported by the EU via the MOODINFLAME project (EU-FP7-HEALTH-F2-2008-222963), the PSYCHAID (EU-FP7-PEOPLE-2009-IAPP-MarieCurie-286334), and the MOODSTRATIFICATION project (H2020-EU. 3.1.1., GA754740). NM and GA were additionally supported by the foundation "Immunitat und Seele." The funders had no role in study design, data collection, analysis and interpretation of data, the writing of the report, and the decision to submit the paper for publication

Evaluation of pre-analytical factors affecting plasma DNA analysis.

Pre-analytical factors can significantly affect circulating cell-free DNA (cfDNA) analysis. However, there are few robust methods to rapidly assess sample quality and the impact of pre-analytical processing. To address this gap and to evaluate effects of DNA extraction methods and blood collection tubes on cfDNA yield and fragment size, we developed a multiplexed droplet digital PCR (ddPCR) assay with 5 short and 4 long amplicons targeting single copy genomic loci. Using this assay, we compared 7 cfDNA extraction kits and found cfDNA yield and fragment size vary significantly. We also compared 3 blood collection protocols using plasma samples from 23 healthy volunteers (EDTA tubes processed within 1 hour and Cell-free DNA Blood Collection Tubes processed within 24 and 72 hours) and found no significant differences in cfDNA yield, fragment size and background noise between these protocols. In 219 clinical samples, cfDNA fragments were shorter in plasma samples processed immediately after venipuncture compared to archived samples, suggesting contribution of background DNA by lysed peripheral blood cells. In summary, we have described a multiplexed ddPCR assay to assess quality of cfDNA samples prior to downstream molecular analyses and we have evaluated potential sources of pre-analytical variation in cfDNA studies