Environmental responses of fruiting fungal communities are phylogenetically structured

Through their ephemeral reproductive structures (fruiting bodies), ectomycorrhizal forest soil fungi provide a resource for a plethora of organisms. Thus, resolving what biotic and abiotic factors determine the occurrence and abundance of fruiting bodies is fundamental for understanding the dynamics of forest trophic networks. While the influence of abiotic factors such as moisture and temperature on fungal fruiting are relatively well established, little is known about how these processes interact with the evolutionary history of fungal species to determine when, where, and in which abundance fungal fruiting bodies will emerge. A specific knowledge gap relates to whether species' responses to their environment are phylogenetically structured. Here, we ask whether related fungal taxa respond similarly to climatic factors and forest habitat characteristics, and whether such correlated responses will affect the assembly of fungal fruiting communities. To resolve these questions, we fitted joint species distribution models combining data on the species composition and abundance of fungal fruiting bodies, environmental variation, and phylogenetic relationships among fungal taxa. Our results show that both site-level forest characteristics (dominant tree species and forest age) and climatic factors related to phenology (effective heat sum) greatly influence the occurrence and abundance of fruiting bodies. More importantly, while different fungal species responded unequally to their shared environment, there was a strong phylogenetic signal in their responses, so that related fungal species tended to fruit under similar environmental conditions. Thus, not only are fruiting bodies short-lived and patchily distributed, but the availability of similar resources will be further aggregated in time and space. These strong constraints on resource availability for fungus-associated taxa highlight the potential of fungus-based networks as a model system for studies on the ecology and evolution of resource-consumer relations in ephemeral systems of high spatiotemporal patchiness

Imprints of latitude, host taxon, and decay stage on fungus-associated arthropod communities

Interactions among fungi and insects involve hundreds of thousands of species. While insect communities on plants have formed some of the classic model systems in ecology, fungus-based communities and the forces structuring them remain poorly studied by comparison. We characterize the arthropod communities associated with fruiting bodies of eight mycorrhizal basidiomycete fungus species from three different orders along a 1200-km latitudinal gradient in northern Europe. We hypothesized that, matching the pattern seen for most insect taxa on plants, we would observe a general decrease in fungal-associated species with latitude. Against this backdrop, we expected local communities to be structured by host identity and phylogeny, with more closely related fungal species sharing more similar communities of associated organisms. As a more unique dimension added by the ephemeral nature of fungal fruiting bodies, we expected further imprints generated by successional change, with younger fruiting bodies harboring communities different from older ones. Using DNA metabarcoding to identify arthropod communities from fungal fruiting bodies, we found that latitude left a clear imprint on fungus-associated arthropod community composition, with host phylogeny and decay stage of fruiting bodies leaving lesser but still-detectable effects. The main latitudinal imprint was on a high arthropod species turnover, with no detectable pattern in overall species richness. Overall, these findings paint a new picture of the drivers of fungus-associated arthropod communities, suggesting that latitude will not affect how many arthropod species inhabit a fruiting body but, rather, what species will occur in it and at what relative abundances (as measured by sequence read counts). These patterns upset simplistic predictions regarding latitudinal gradients in species richness and in the strength of biotic interactions.Peer reviewe

Crystal Structure of Human Cytosolic 5′-Nucleotidase II INSIGHTS INTO ALLOSTERIC REGULATION AND SUBSTRATE RECOGNITION

Cytosolic 5′-nucleotidase II catalyzes the dephosphorylation of 6-hydroxypurine nucleoside 5′-monophosphates and regulates the IMP and GMP pools within the cell. It possesses phosphotransferase activity and thereby also catalyzes the reverse reaction. Both reactions are allosterically activated by adenine-based nucleotides and 2,3-bisphosphoglycerate. We have solved structures of cytosolic 5′-nucleotidase II as native protein (2.2 A) and in complex with adenosine (1.5A) and beryllium trifluoride (2.15A). The tetrameric enzyme is structurally similar to enzymes of the haloacid dehalogenase (HAD) superfamily, including mitochondrial 5′(3′)-deoxyribonucleotidase and cytosolic 5′-nucleotidase III but possesses additional regulatory regions that contain two allosteric effector sites. At effector site 1 located near a subunit interface we modeled diadenosine tetraphosphate with one adenosine moiety in each subunit. This efficiently glues the tetramer subunits together in pairs. The model shows why diadenosine tetraphosphate but not diadenosine triphosphate activates the enzyme and supports a role for cN-II during apoptosis when the level of diadenosine tetraphosphate increases. We have also modeled 2,3-bisphosphoglycerate in effector site 1 using one phosphate site from each subunit. By comparing the structure of cytosolic 5′-nucleotidase II with that of mitochondrial 5′(3′)-deoxyribonucleotidase in complex with dGMP, we identified residues involved in substrate recognition

Completing the family portrait of the anti-apoptotic Bcl-2 proteins: Crystal structure of human Bfl-1 in complex with Bim

AbstractEvasion of apoptosis is recognized as a characteristic of malignant growth. Anti-apoptotic B-cell lymphoma-2 (Bcl-2) family members have therefore emerged as potential therapeutic targets due to their critical role in proliferating cancer cells. Here, we present the crystal structure of Bfl-1, the last anti-apoptotic Bcl-2 family member to be structurally characterized, in complex with a peptide corresponding to the BH3 region of the pro-apoptotic protein Bim. The structure reveals distinct features at the peptide-binding site, likely to define the binding specificity for pro-apoptotic proteins. Superposition of the Bfl-1:Bim complex with that of Mcl-1:Bim reveals a significant local plasticity of hydrophobic interactions contributed by the Bim peptide, likely to be the basis for the multi specificity of Bim for anti-apoptotic proteins

The Crystal Structure of the Dachshund Domain of Human SnoN Reveals Flexibility in the Putative Protein Interaction Surface

The human SnoN is an oncoprotein that interacts with several transcription-regulatory proteins such as the histone-deacetylase, N-CoR containing co-repressor complex and Smad proteins. This study presents the crystal structure of the Dachshund homology domain of human SnoN. The structure reveals a groove composed of conserved residues with characteristic properties of a protein-interaction surface. A comparison of the 12 monomers in the asymmetric unit reveals the presence of two major conformations: an open conformation with a well accessible groove and a tight conformation with a less accessible groove. The variability in the backbone between the open and the tight conformations matches the differences seen in previously determined structures of individual Dachshund homology domains, suggesting a general plasticity within this fold family. The flexibility observed in the putative protein binding groove may enable SnoN to recognize multiple interaction partners

Imprints of latitude, host taxon, and decay stage on fungus-associated arthropod communities

Interactions among fungi and insects involve hundreds of thousands of species. While insect communities on plants have formed some of the classic model systems in ecology, fungus-based communities and the forces structuring them remain poorly studied by comparison. We characterize the arthropod communities associated with fruiting bodies of eight mycorrhizal basidiomycete fungus species from three different orders along a 1200-km latitudinal gradient in northern Europe. We hypothesized that, matching the pattern seen for most insect taxa on plants, we would observe a general decrease in fungal-associated species with latitude. Against this backdrop, we expected local communities to be structured by host identity and phylogeny, with more closely related fungal species sharing more similar communities of associated organisms. As a more unique dimension added by the ephemeral nature of fungal fruiting bodies, we expected further imprints generated by successional change, with younger fruiting bodies harboring communities different from older ones. Using DNA metabarcoding to identify arthropod communities from fungal fruiting bodies, we found that latitude left a clear imprint on fungus-associated arthropod community composition, with host phylogeny and decay stage of fruiting bodies leaving lesser but still-detectable effects. The main latitudinal imprint was on a high arthropod species turnover, with no detectable pattern in overall species richness. Overall, these findings paint a new picture of the drivers of fungus-associated arthropod communities, suggesting that latitude will not affect how many arthropod species inhabit a fruiting body but, rather, what species will occur in it and at what relative abundances (as measured by sequence read counts). These patterns upset simplistic predictions regarding latitudinal gradients in species richness and in the strength of biotic interactions.</p

Structural studies of tri-functional human GART

Human purine de novo synthesis pathway contains several multi-functional enzymes, one of which, tri-functional GART, contains three enzymatic activities in a single polypeptide chain. We have solved structures of two domains bearing separate catalytic functions: glycinamide ribonucleotide synthetase and aminoimidazole ribonucleotide synthetase. Structures are compared with those of homologous enzymes from prokaryotes and analyzed in terms of the catalytic mechanism. We also report small angle X-ray scattering models for the full-length protein. These models are consistent with the enzyme forming a dimer through the middle domain. The protein has an approximate seesaw geometry where terminal enzyme units display high mobility owing to flexible linker segments. This resilient seesaw shape may facilitate internal substrate/product transfer or forwarding to other enzymes in the pathway

Generational Association Studies of Dopaminergic Genes in Reward Deficiency Syndrome (RDS) Subjects: Selecting Appropriate Phenotypes for Reward Dependence Behaviors

Abnormal behaviors involving dopaminergic gene polymorphisms often reflect an insufficiency of usual feelings of satisfaction, or Reward Deficiency Syndrome (RDS). RDS results from a dysfunction in the “brain reward cascade,” a complex interaction among neurotransmitters (primarily dopaminergic and opioidergic). Individuals with a family history of alcoholism or other addictions may be born with a deficiency in the ability to produce or use these neurotransmitters. Exposure to prolonged periods of stress and alcohol or other substances also can lead to a corruption of the brain reward cascade function. We evaluated the potential association of four variants of dopaminergic candidate genes in RDS (dopamine D1 receptor gene [DRD1]; dopamine D2 receptor gene [DRD2]; dopamine transporter gene [DAT1]; dopamine beta-hydroxylase gene [DBH]). Methodology: We genotyped an experimental group of 55 subjects derived from up to five generations of two independent multiple-affected families compared to rigorously screened control subjects (e.g., N = 30 super controls for DRD2 gene polymorphisms). Data related to RDS behaviors were collected on these subjects plus 13 deceased family members. Results: Among the genotyped family members, the DRD2 Taq1 and the DAT1 10/10 alleles were significantly (at least p < 0.015) more often found in the RDS families vs. controls. The TaqA1 allele occurred in 100% of Family A individuals (N = 32) and 47.8% of Family B subjects (11 of 23). No significant differences were found between the experimental and control positive rates for the other variants. Conclusions: Although our sample size was limited, and linkage analysis is necessary, the results support the putative role of dopaminergic polymorphisms in RDS behaviors. This study shows the importance of a nonspecific RDS phenotype and informs an understanding of how evaluating single subset behaviors of RDS may lead to spurious results. Utilization of a nonspecific “reward” phenotype may be a paradigm shift in future association and linkage studies involving dopaminergic polymorphisms and other neurotransmitter gene candidates

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D