Strain identity of the ectomycorrhizal fungus Laccaria bicolor is more important than richness in regulating plant and fungal performance under nutrient rich conditions

This work was funded by the Natural Environment Research Council (NE/I014527/1).Peer reviewedPublisher PD

The health of women and girls determines the health and well-being of our modern world: A White Paper From the International Council on Women's Health Issues

The International Council on Women's Health Issues (ICOWHI) is an international nonprofit association dedicated to the goal of promoting health, health care, and well-being of women and girls throughout the world through participation, empowerment, advocacy, education, and research. We are a multidisciplinary network of women's health providers, planners, and advocates from all over the globe. We constitute an international professional and lay network of those committed to improving women and girl's health and quality of life. This document provides a description of our organization mission, vision, and commitment to improving the health and well-being of women and girls globally

A new hammer to crack an old nut : interspecific competitive resource capture by plants is regulated by nutrient supply, not climate

Peer reviewedPublisher PD

Spatial Effects and GWA Mapping of Root Colonization Assessed in the Interaction Between the Rice Diversity Panel 1 and an Arbuscular Mycorrhizal Fungus

The majority of the research reported here is an output of EU project “EURoot” (FP7-KBBE-2011-5 Grant Agreement No. 289300) project. RS’s contribution was funded by FACCE-JPI NET project “GreenRice” (Sustainable and environmental friendly rice cultivation systems in Europe) and was funded by the BBSRC award BB/M018415/1.Peer reviewedPublisher PD

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Thermal adaptation of soil microbial respiration to elevated temperature

In the short-term heterotrophic soil respiration is strongly and positively related to temperature. In the long-term, its response to temperature is uncertain. One reason for this is because in field experiments increases in respiration due to warming are relatively short-lived. The explanations proposed for this ephemeral response include depletion of fast-cycling, soil carbon pools and thermal adaptation of microbial respiration. Using a > 15 year soil warming experiment in a mid-latitude forest, we show that the apparent 'acclimation' of soil respiration at the ecosystem scale results from combined effects of reductions in soil carbon pools and microbial biomass, and thermal adaptation of microbial respiration. Mass-specific respiration rates were lower when seasonal temperatures were higher, suggesting that rate reductions under experimental warming likely occurred through temperature-induced changes in the microbial community. Our results imply that stimulatory effects of global temperature rise on soil respiration rates may be lower than currently predicted

DNMT3B PWWP mutations cause hypermethylation of heterochromatin

The correct establishment of DNA methylation patterns is vital for mammalian development and is achieved by the de novo DNA methyltransferases DNMT3A and DNMT3B. DNMT3B localises to H3K36me3 at actively transcribing gene bodies via its PWWP domain. It also functions at heterochromatin through an unknown recruitment mechanism. Here we find that knockout of DNMT3B causes loss of methylation predominantly at H3K9me3-marked heterochromatin and that DNMT3B PWWP domain mutations or deletion result in striking increases of methylation in H3K9me3-marked heterochromatin. Removal of the N-terminal region of DNMT3B affects its ability to methylate H3K9me3-marked regions. This region of DNMT3B directly interacts with HP1 and facilitates the bridging of DNMT3B with H3K9me3-marked nucleosomes in vitro. Our results suggest that DNMT3B is recruited to H3K9me3 marked heterochromatin in a PWWP-independent mannerthat is facilitated by the protein’s N-terminal region through an interaction with a key heterochromatin protein. More generally, we suggest that DNMT3B plays a role in DNA methylation homeostasis at heterochromatin, a process which is disrupted in cancer, aging and Immunodeficiency, Centromeric Instability and Facial Anomalies (ICF) syndrome

PKA Phosphorylation of NDE1 Is DISC1/PDE4 Dependent and Modulates Its Interaction with LIS1 and NDEL1

Nuclear distribution factor E-homolog 1 (NDE1), Lissencephaly 1 (LIS1), and NDE-like 1 (NDEL1) together participate in essential neurodevelopmental processes, including neuronal precursor proliferation and differentiation, neuronal migration, and neurite out-growth. NDE1/LIS1/NDEL1 interacts with Disrupted in Schizophrenia 1 (DISC1) and the cAMP-hydrolyzing enzyme phosphodiesterase 4 (PDE4). DISC1, PDE4, NDE1, and NDEL1 have each been implicated as genetic risk factors for major mental illness. Here, we demonstrate that DISC1 and PDE4 modulate NDE1 phosphorylation by cAMP-dependent protein kinase A (PKA) and identify a novel PKA substrate site on NDE1 at threonine-131 (T131). Homology modeling predicts that phosphorylation at T131 modulates NDE1–LIS1 and NDE1–NDEL1 interactions, which we confirm experimentally. DISC1–PDE4 interaction thus modulates organization of the NDE1/NDEL1/LIS1 complex. T131-phosphorylated NDE1 is present at the postsynaptic density, in proximal axons, within the nucleus, and at the centrosome where it becomes substantially enriched during mitosis. Mutation of the NDE1 T131 site to mimic PKA phosphorylation inhibits neurite outgrowth. Thus PKA-dependent phosphorylation of the NDE1/LIS1/NDEL1 complex is DISC1–PDE4 modulated and likely to regulate its neural functions

DISC1 regulates N-methyl-D-aspartate receptor dynamics:abnormalities induced by a <i>Disc1 </i>mutation modelling a translocation linked to major mental illness

The neuromodulatory gene DISC1 is disrupted by a t(1;11) translocation that is highly penetrant for schizophrenia and affective disorders, but how this translocation affects DISC1 function is incompletely understood. N-methyl-D-aspartate receptors (NMDAR) play a central role in synaptic plasticity and cognition, and are implicated in the pathophysiology of schizophrenia through genetic and functional studies. We show that the NMDAR subunit GluN2B complexes with DISC1-associated trafficking factor TRAK1, while DISC1 interacts with the GluN1 subunit and regulates dendritic NMDAR motility in cultured mouse neurons. Moreover, in the first mutant mouse that models DISC1 disruption by the translocation, the pool of NMDAR transport vesicles and surface/synaptic NMDAR expression are increased. Since NMDAR cell surface/synaptic expression is tightly regulated to ensure correct function, these changes in the mutant mouse are likely to affect NMDAR signalling and synaptic plasticity. Consistent with these observations, RNASeq analysis of the translocation carrier-derived human neurons indicates abnormalities of excitatory synapses and vesicle dynamics. RNASeq analysis of the human neurons also identifies many differentially expressed genes previously highlighted as putative schizophrenia and/or depression risk factors through large-scale genome-wide association and copy number variant studies, indicating that the translocation triggers common disease pathways that are shared with unrelated psychiatric patients. Altogether, our findings suggest that translocation-induced disease mechanisms are likely to be relevant to mental illness in general, and that such disease mechanisms include altered NMDAR dynamics and excitatory synapse function. This could contribute to the cognitive disorders displayed by translocation carriers.</p

DNMT3B PWWP mutations cause hypermethylation of heterochromatin

The correct establishment of DNA methylation patterns is vital for mammalian development and is achieved by the de novo DNA methyltransferases DNMT3A and DNMT3B. DNMT3B localises to H3K36me3 at actively transcribing gene bodies via its PWWP domain. It also functions at heterochromatin through an unknown recruitment mechanism. Here, we find that knockout of DNMT3B causes loss of methylation predominantly at H3K9me3-marked heterochromatin and that DNMT3B PWWP domain mutations or deletion result in striking increases of methylation in H3K9me3-marked heterochromatin. Removal of the N-terminal region of DNMT3B affects its ability to methylate H3K9me3-marked regions. This region of DNMT3B directly interacts with HP1α and facilitates the bridging of DNMT3B with H3K9me3-marked nucleosomes in vitro. Our results suggest that DNMT3B is recruited to H3K9me3-marked heterochromatin in a PWWP-independent manner that is facilitated by the protein’s N-terminal region through an interaction with a key heterochromatin protein. More generally, we suggest that DNMT3B plays a role in DNA methylation homeostasis at heterochromatin, a process which is disrupted in cancer, aging and Immunodeficiency, Centromeric Instability and Facial Anomalies (ICF) syndrome