Functional diversity of leaf nitrogen concentrations drives grassland carbon fluxes

Little is known about the role of plant functional diversity for ecosystem‐level carbon (C) fluxes. To fill this knowledge gap, we translocated monoliths hosting communities with four and 16 sown species from a long‐term grassland biodiversity experiment (‘The Jena Experiment’) into a controlled environment facility for ecosystem research (Ecotron). This allowed quantifying the effects of plant diversity on ecosystem C fluxes as well as three parameters of C uptake efficiency (water and nitrogen use efficiencies and apparent quantum yield). By combining data on ecosystem C fluxes with vegetation structure and functional trait‐based predictors, we found that increasing plant species and functional diversity led to higher gross and net ecosystem C uptake rates. Path analyses and light response curves unravelled the diversity of leaf nitrogen concentration in the canopy as a key functional predictor of C fluxes, either directly or indirectly via LAI and aboveground biomass.     

Bird's nest fungi (Nidulariales: Nidulariaceae) in Baltic and Dominican amber

Nidula baltica sp. nov. and Cyathus dominicanus sp. nov. are described from Cenozoic Baltic and Dominican amber. These are the first fossil members of the Family Nidulariaceae and show that the basic characteristics of this group were already established some 40–50 million years ago.     

A brief overview of amyloids and Alzheimer’s disease

Amyloid fibrils are self-assembled fibrous protein aggregates that are associated with a number of presently incurable diseases such as Alzheimer’s and Parkinson’s disease. Millions of people worldwide suffer from amyloid diseases. This review summarizes the unique cross-β structure of amyloid fibrils, morphological variations, the kinetics of amyloid fibril formation, and the cytotoxic effects of these fibrils and oligomers. Alzheimer’s disease is also explored as an example of an amyloid disease to show the various approaches to treat these amyloid diseases. Finally, this review investigates the nanotechnological and biological applications of amyloid fibrils; as well as a summary of the typical biological pathways involved in the disposal of amyloid fibrils and their precursors.     

A Century of Elk Restoration in Eastern North America

Over a century has passed since elk were extirpated in eastern North America. During that time, numerous attempts to reintroduce elk into eastern North America have resulted in varying degrees of success and failure. An overview of restoration efforts during the last 100 years is presented here with emphasis on the differences in rates of population change among regions and differences in major causes of elk mortality during both the pre‐ and post‐acclimation periods. Approximately 40% of recorded elk reintroduction attempts in eastern North America resulted in failure, with the majority of these having occurred in the first half of the 20th century. Although rates of population change in elk were highly variable, they were not related to founding population size. Major causes of mortality varied among regions and should be considered in future reintroduction attempts.     

SitA contributes to the virulence of Klebsiella pneumoniae in a mouse infection model

Klebsiella pneumoniae is an opportunistic pathogen, which causes a wide range of nosocomial infections. Recently, antibiotic resistance makes K. pneumoniae infection difficult to deal with. Investigation on virulence determinants of K. pneumoniae can provide more information about pathogenesis and unveil new targets for treatment or vaccine development. In this study, SitA, a Fur-regulated divalent cation transporter, was found significantly increased when K. pneumoniae was cultured in a nutrient-limited condition. A sitA-deletion strain (ΔsitA) was created to characterize the importance of SitA in virulence. ΔsitA showed higher sensitivity toward hydroperoxide than its parental strain. In a mouse intraperitoneal infection model, the survival rate of mice infected with ΔsitA strain increased greatly when compared with that of mice infected with the parental strain, suggesting that sitA deletion attenuates the bacterial virulence in vivo. To test whether ΔsitA strain is a potential vaccine candidate, mice were immunized with inactivated bacteria and then challenged with the wild-type strain. The results showed that using ΔsitA mutant protected mice better than using the wild-type strain or the capsule-negative congenic bacteria. In summary, SitA was found being important for the growth of K. pneumoniae in vivo and deleting sitA might be a potential approach to generate vaccines against K. pneumoniae.     

Interactions between cadherin-11 and platelet-derived growth factor receptor-alpha signaling link cell adhesion and proliferation

Cadherins are homophilic cell-to-cell adhesion molecules that help cells respond to environmental changes. Newly formed cadherin junctions are associated with increased cell phosphorylation, but the pathways driving this signaling response are largely unknown. Since cadherins have no intrinsic signaling activity, this phosphorylation must occur through interactions with other signaling molecules. We previously reported that cadherin-11 engagement activates joint synovial fibroblasts, promoting inflammatory and degradative pathways important in rheumatoid arthritis (RA) pathogenesis. Our objective in this study was to discover interacting partners that mediate cadherin-11 signaling. Protein array screening showed that cadherin-11 extracellular binding domains linked to an Fc domain (cad11Fc) induced platelet-derived growth factor (PDGFR)-α phosphorylation in synovial fibroblasts and glioblastoma cells. PDGFRs are growth factor receptor tyrosine kinases that promote cell proliferation, survival, and migration in mesodermally derived cells. Increased PDGFR activity is implicated in RA pathology and associates with poor prognosis in several cancers, including sarcoma and glioblastoma. PDGFRα activation by cadherin-11 signaling promoted fibroblast proliferation, a signaling pathway independent from cadherin-11-stimulated IL-6 or matrix metalloproteinase (MMP)-3 release. PDGFRα phosphorylation mediated most of the cad11Fc-induced phosphatidyl-3-kinase (PI3K)/Akt activation, but only part of the mitogen-activated protein kinase (MAPK) response. PDGFRα-dependent signaling did not require cell cadherin-11 expression. Rather, cad11Fc immunoprecipitated PDGFRα, indicating a direct interaction between cadherin-11 and PDGFRα extracellular domains. This study is the first to report an interaction between cadherin-11 and PDGFRα and adds to our growing understanding that cadherin-growth factor receptor interactions help balance the interplay between tissue growth and adhesion.     

Functional insight into LOAD-associated microglial response genes

Alzheimer''s disease (AD) is characterized by the presence of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs), neuronal and synaptic loss and inflammation of the central nervous system (CNS). The majority of AD research has been dedicated to the understanding of two major AD hallmarks (i.e. Aβ and NFTs); however, recent genome-wide association studies (GWAS) data indicate neuroinflammation as having a critical role in late-onset AD (LOAD) development, thus unveiling a novel avenue for AD therapeutics. Recent evidence has provided much support to the innate immune system''s involvement with AD progression; however, much remains to be uncovered regarding the role of glial cells, specifically microglia, in AD. Moreover, numerous variants in immune and/or microglia-related genes have been identified in whole-genome sequencing and GWAS analyses, including such genes as TREM2, CD33, APOE, API1, MS4A, ABCA7, BIN1, CLU, CR1, INPP5D, PICALM and PLCG2. In this review, we aim to provide an insight into the function of the major LOAD-associated microglia response genes.     

Structural basis for feedforward control in the PINK1/Parkin pathway

PINK1 and parkin constitute a mitochondrial quality control system mutated in Parkinson’s disease. PINK1, a kinase, phosphorylates ubiquitin to recruit parkin, an E3 ubiquitin ligase, to mitochondria. PINK1 controls both parkin localization and activity through phosphorylation of both ubiquitin and the ubiquitin‐like (Ubl) domain of parkin. Here, we observed that phospho‐ubiquitin can bind to two distinct sites on parkin, a high‐affinity site on RING1 that controls parkin localization and a low‐affinity site on RING0 that releases parkin autoinhibition. Surprisingly, ubiquitin vinyl sulfone assays, ITC, and NMR titrations showed that the RING0 site has higher affinity for phospho‐ubiquitin than phosphorylated Ubl in trans. We observed parkin activation by micromolar concentrations of tetra‐phospho‐ubiquitin chains that mimic mitochondria bearing multiple phosphorylated ubiquitins. A chimeric form of parkin with the Ubl domain replaced by ubiquitin was readily activated by PINK1 phosphorylation. In all cases, mutation of the binding site on RING0 abolished parkin activation. The feedforward mechanism of parkin activation confers robustness and rapidity to the PINK1‐parkin pathway and likely represents an intermediate step in its evolutionary development.     

Identification of core genes in prefrontal cortex and hippocampus of Alzheimer's disease based on mRNA‐miRNA network

Alzheimer''s disease (AD) is a neurodegenerative disorder with cognitive impairment and abnormal mental behaviour. There is currently no effective cure. The development of early diagnostic markers and the mining of potential therapeutic targets are one of the important strategies. This study aimed to explore potential biomarkers or therapeutic targets related to AD in the hippocampus and prefrontal cortex, two brain regions highly related to AD. Differentially expressed genes and miRNAs between AD patients and healthy controls were obtained from the Gene Expression Omnibus database. The mRNA‐miRNA network was constructed and key genes involved in AD were screened out by protein–protein interaction analysis, and were subsequently verified by independent datasets and qPCR in an AD mouse model. Our findings showed that six hub genes including CALN1, TRPM7, ATR, SOCS3, MOB3A and OGDH were believed to be involved in the pathogenesis of AD. Western blot analysis further determined that CALN1, ATR and OGDH were the possible biomarkers and therapeutic targets for AD. In addition, 6 possible miRNAs biomarkers have also been verified by qPCR on AD animal models. Our findings may benefit clinical diagnosis and early prevention of AD.