Trehalose-6-Phosphate: Connecting Plant Metabolism and Development

Beyond their metabolic roles, sugars can also act as messengers in signal transduction. Trehalose, a sugar found in many species of plants and animals, is a non-reducing disaccharide composed of two glucose moieties. Its synthesis in plants is a two-step process, involving the production of trehalose-6-phosphate (T6P) catalyzed by trehalose-6-phosphate synthase (TPS) and its consecutive dephosphorylation to trehalose, catalyzed by trehalose-6-phosphate phosphatase (TPP). T6P has recently emerged as an important signaling metabolite, regulating carbon assimilation and sugar status in plants. In addition, T6P has also been demonstrated to play an essential role in plant development. This review recapitulates the recent advances we have made in understanding the role of T6P in coordinating diverse metabolic and developmental processes

The FANTASTIC FOUR proteins influence shoot meristem size in Arabidopsis thaliana

<p>Abstract</p> <p>Background</p> <p>Throughout their lives plants produce new organs from groups of pluripotent cells called meristems, located at the tips of the shoot and the root. The size of the shoot meristem is tightly controlled by a feedback loop, which involves the homeodomain transcription factor WUSCHEL (WUS) and the CLAVATA (CLV) proteins. This regulatory circuit is further fine-tuned by morphogenic signals such as hormones and sugars.</p> <p>Results</p> <p>Here we show that a family of four plant-specific proteins, encoded by the <it>FANTASTIC FOUR </it>(<it>FAF</it>) genes, has the potential to regulate shoot meristem size in <it>Arabidopsis thaliana</it>. <it>FAF2 </it>and <it>FAF4 </it>are expressed in the centre of the shoot meristem, overlapping with the site of <it>WUS </it>expression. Consistent with a regulatory interaction between the <it>FAF </it>gene family and <it>WUS</it>, our experiments indicate that the FAFs can repress <it>WUS</it>, which ultimately leads to an arrest of meristem activity in <it>FAF </it>overexpressing lines. The finding that meristematic expression of <it>FAF2 </it>and <it>FAF4 </it>is under negative control by CLV3 further supports the hypothesis that the FAFs are modulators of the genetic circuit that regulates the meristem.</p> <p>Conclusion</p> <p>This study reports the initial characterization of the <it>Arabidopsis thaliana FAF </it>gene family. Our data indicate that the <it>FAF </it>genes form a plant specific gene family, the members of which have the potential to regulate the size of the shoot meristem by modulating the CLV3-WUS feedback loop.</p

Acute Downregulation but Not Genetic Ablation of Murine MCU Impairs Suppressive Capacity of Regulatory CD4 T Cells

By virtue of mitochondrial control of energy production, reactive oxygen species (ROS) generation, and maintenance of Ca2+ homeostasis, mitochondria play an essential role in modulating T cell function. The mitochondrial Ca2+ uniporter (MCU) is the pore-forming unit in the main protein complex mediating mitochondrial Ca2+ uptake. Recently, MCU has been shown to modulate Ca2+ signals at subcellular organellar interfaces, thus fine-tuning NFAT translocation and T cell activation. The mechanisms underlying this modulation and whether MCU has additional T cell subpopulationspecific effects remain elusive. However, mice with germline or tissue-specific ablation of Mcu did not show impaired T cell responses in vitro or in vivo, indicating that ‘chronic’ loss of MCU can be functionally compensated in lymphocytes. The current work aimed to specifically investigate whether and how MCU influences the suppressive potential of regulatory CD4 T cells (Treg). We show that, in contrast to genetic ablation, acute siRNA-mediated downregulation of Mcu in murine Tregs results in a significant reduction both in mitochondrial Ca2+ uptake and in the suppressive capacity of Tregs, while the ratios of Treg subpopulations and the expression of hallmark transcription factors were not affected. These findings suggest that permanent genetic inactivation of MCU may result in compensatory adaptive mechanisms, masking the effects on the suppressive capacity of Tregs

Inflammatory bowel disease addressed by Caco-2 and monocyte-derived macrophages : an opportunity for an in vitro drug screening assay

Infammatory bowel disease (IBD) is a widespread disease, afecting a growing demographic. The treatment of chronic infammation located in the GI-tract is dependent on the severity; therefore, the IBD treatment pyramid is commonly applied. Animal experimentation plays a key role for novel IBD drug development; nevertheless, it is ethically questionable and limited in its throughput. Reliable and valid in vitro assays ofer the opportunity to overcome these limitations. We combined Caco-2 with monocyte-derived macrophages and exposed them to known drugs, targeting an in vitro-in vivo correlation (IVIVC) with a focus on the severity level and its related drug candidate. This co-culture assay addresses namely the intestinal barrier and the immune response in IBD. The drug efcacy was analyzed by an LPS-infammation of the co-culture and drug exposure according to the IBD treatment pyramid. Efcacy was defned as the range between LPS control (0%) and untreated co-culture (100%) independent of the investigated read-out (TEER, Papp, cytokine release: IL-6, IL-8, IL-10, TNF-α). The release of IL-6, IL-8, and TNF-α was identifed as an appropriate readout for a fast drug screening (“yes–no response”). TEER showed a remarkable IVIVC correlation to the human treatment pyramid (5-ASA, Prednisolone, 6-mercaptopurine, and infiximab) with an R2 of 0.68. Similar to the description of an adverse outcome pathway (AOP) framework, we advocate establishing an “Efcacy Outcome Pathways (EOPs)” framework for drug efcacy assays. The in vitro assay ofers an easy and scalable method for IBD drug screening with a focus on human data, which requires further validation

Invasion of a Legume Ecosystem Engineer in a Cold Biome Alters Plant Biodiversity

Plant ecosystem engineers are widely used to combat land degradation. However, the ability of those plants to modulate limiting abiotic and biotic resources of other species can cause damage to ecosystems in which they become invasive. Here, we use Lupinus nootkatensis as example to estimate and project the hazardous potential of nitrogen fixing herbaceous plants in a sub-polar oceanic climate. L. nootkatensis was introduced to Iceland in the 1940s to address erosion problems and foster reforestation, but subsequently became a high-latitude invader. In a local field survey, we quantified the impact of L. nootkatensis invasion at three different cover levels (0, 10–50, and 51–100%) upon native plant diversity, richness, and community composition of heath-, wood-, and grasslands using a pairwise comparison design and comparisons of means. Afterward, we scaled impacts up to the ecosystem and landscape level by relating occurrences of L. nootkatensis to environmental and human-mediated variables across Iceland using a species distribution model. Plant diversity was significantly deteriorated under high lupine cover levels of the heath- and woodland, but not in the grassland. Plant species richness of the most diverse habitat, the heathland, linearly decreased with lupine cover level. The abundance of small rosettes, cushion plants, orchids, and small woody long-lived plants of the heath declined with invader presence, while the abundance of late successional species and widespread nitrophilous ruderals in wood- and grasslands increased. Distribution modeling revealed 13.3% of Iceland’s land surface area to be suitable lupine habitat. Until 2061–2080, this area will more than double and expand significantly into the Central Highlands due to human mediation and increasingly favorable climatic conditions. Species-rich habitats showed a loss of plant species diversity and richness as well as a change in community composition even in low lupine cover classes. The future increase of suitable lupine habitat might lead to the displacement of cold-adapted native plant species and will certainly challenge conservation as well as restoration of ecosystems in the cold climate of Iceland, but also elsewhere. Lupine invasion speeds up succession, which may be additive with climate change effects, and accelerates ecological change in cold biomes

Synchronization of developmental, molecular and metabolic aspects of source–sink interactions

Plants have evolved a multitude of strategies to adjust their growth according to external and internal signals. Interconnected metabolic and phytohormonal signalling networks allow adaption to changing environmental and developmental conditions and ensure the survival of species in fluctuating environments. In agricultural ecosystems, many of these adaptive responses are not required or may even limit crop yield, as they prevent plants from realizing their fullest potential. By lifting source and sink activities to their maximum, massive yield increases can be foreseen, potentially closing the future yield gap resulting from an increasing world population and the transition to a carbon-neutral economy. To do so, a better understanding of the interplay between metabolic and developmental processes is required. In the past, these processes have been tackled independently from each other, but coordinated efforts are required to understand the fine mechanics of source–sink relations and thus optimize crop yield. Here, we describe approaches to design high-yielding crop plants utilizing strategies derived from current metabolic concepts and our understanding of the molecular processes determining sink development.Research in the authors’ laboratories was supported by the following grants: the cassava source–sink (CASS) project of the Bill and Melinda Gates Foundation (to A.R.F., H.E.N., M.S. and U.S.); the ERA-CAPs project SourSi (to A.R.F. and L.J.S.); the BIO2015-3019-EXP grant from the Spanish Ministry of Economy, Industry and Competitiveness and the PCIN-2017-032 CONCERT-JAPAN project financed by the Ministry of Science, Innovation and Universities (to S.P.); Australian Research Council DP180103834 (to Y.L.R.); the US National Science Foundation (grant no. IOS-1457183); the Agriculture and Food Research Initiative (AFRI; grant no. 2017-67013-26158) from the USDA National Institute of Food and Agriculture (to M.T.); the Finnish Centre of Excellence in Molecular Biology of Primary Producers (Academy of Finland CoE program 2014–2019; grant no. 271832); the Gatsby Foundation (grant no. GAT3395/PR3); the University of Helsinki (grant no. 799992091); the European Research Council Advanced Investigator Grant SYMDEV (grant no. 323052; to Y.H.); the BMBF (grant no. 031B0191); the DFG (SPP1530: WA3639/1-2, 2-1); and the Max-Planck-Society (to V.W.). We additionally thank D. Ko and R. Ruonala for their comments on the manuscript

Ovulation is triggered by a cyclical modulation of gonadotropes into a hyperexcitable state

Gonadotropes in the anterior pituitary gland are essential for fertility and provide a functional link between the brain and the gonads. To trigger ovulation, gonadotrope cells release massive amounts of luteinizing hormone (LH). The mechanism underlying this remains unclear. Here, we utilize a mouse model expressing a genetically encoded Ca2+ indicator exclusively in gonadotropes to dissect this mechanism in intact pituitaries. We demonstrate that female gonadotropes exclusively exhibit a state of hyperexcitability during the LH surge, resulting in spontaneous [Ca2+]i transients in these cells, which persist in the absence of any in vivo hormonal signals. L-type Ca2+ channels and transient receptor potential channel A1 (TRPA1) together with intracellular reactive oxygen species (ROS) levels ensure this state of hyperexcitability. Consistent with this, virus-assisted triple knockout of Trpa1 and L-type Ca2+ subunits in gonadotropes leads to vaginal closure in cycling females. Our data provide insight into molecular mechanisms required for ovulation and reproductive success in mammals

Bitter taste cells in the ventricular walls of the murine brain regulate glucose homeostasis

The median eminence (ME) is a circumventricular organ at the base of the brain that controls body homeostasis. Tanycytes are its specialized glial cells that constitute the ventricular walls and regulate different physiological states, however individual signaling pathways in these cells are incompletely understood. Here, we identify a functional tanycyte subpopulation that expresses key taste transduction genes including bitter taste receptors, the G protein gustducin and the gustatory ion channel TRPM5 (M5). M5 tanycytes have access to blood-borne cues via processes extended towards diaphragmed endothelial fenestrations in the ME and mediate bidirectional communication between the cerebrospinal fluid and blood. This subpopulation responds to metabolic signals including leptin and other hormonal cues and is transcriptionally reprogrammed upon fasting. Acute M5 tanycyte activation induces insulin secretion and acute diphtheria toxin-mediated M5 tanycyte depletion results in impaired glucose tolerance in diet-induced obese mice. We provide a cellular and molecular framework that defines how bitter taste cells in the ME integrate chemosensation with metabolism

250 labels used to stigmatise people with mental illness

<p>Abstract</p> <p>Background</p> <p>The stigma against people with mental illness is a major barrier to help-seeking in young people for mental health problems. The objective of this study was to investigate the extent of stigma in relation to treatment avoidance in 14 year-old school students in England in relation to how they refer to people with mental illness.</p> <p>Methods</p> <p>This is a qualitative, cross-sectional study. The data were gathered as part of the baseline assessment for an intervention study intended to reduce stigma among 14 year old school students. The participating schools were two grammar (selective) schools and three comprehensive (non-selective) schools. At the start of the lesson, the students were asked 'What sorts of words or phrases might you use to describe someone who experiences mental health problems?' Words and terms used to refer to mental illness were enumerated. Using the grounded theory approach, words and terms were grouped in terms of their denotative and connotative meanings. Labels were then derived to capture the key themes attached by the students to the concepts of mental illness. The frequencies of occurrence for each word were also tabulated.</p> <p>Results</p> <p>400 of the 472 participating students (85%) provided 250 words and terms to describe a person with mental illness. Five themes were identified from the data. The first theme called 'popular derogatory terms' (116 items) accounted for nearly half of the words examined. The second theme occurred less often and was described as 'negative emotional state' (61 items). The third theme demonstrated the confusion of young people between physical disabilities, learning difficulties and mental health problems (38 items). The use of psychiatric diagnoses (15 items) and terms related to violence (9 items) were unexpectedly uncommon.</p> <p>Conclusion</p> <p>Our findings suggest the hypothesis that help-seeking by mentally ill young people may be improved by interventions that address both their lack of factual information about mental illness, and those which reduce their strong negative emotional reactions towards people with mental illness.</p