Where am I and why? Synthesizing range biology and the eco‐evolutionary dynamics of dispersal

Although generations of researchers have studied the factors that limit the distributions of species, we still do not seem to understand this phenomenon comprehensively. Traditionally, species’ ranges have been seen as the consequence of abiotic conditions and local adaptation to the environment. However, during the last years it has become more and more evident that biotic factors – such as intra‐ and interspecific interactions or the dispersal capacity of species – and even rapidly occurring evolutionary processes can strongly influence the range of a species and its potential to spread to new habitats. Relevant eco‐evolutionary forces can be found at all hierarchical levels: from landscapes to communities via populations, individuals and genes. We here use the metapopulation concept to develop a framework that allows us to synthesize this broad spectrum of different factors. Since species’ ranges are the result of a dynamic equilibrium of colonization and local extinction events, the importance of dispersal is immediately clear. We highlight the complex interrelations and feedbacks between ecological and evolutionary forces that shape dispersal and result in non‐trivial and partially counter‐intuitive range dynamics. Our concept synthesizes current knowledge on range biology and the eco‐evolutionary dynamics of dispersal. Synthesis What factors are responsible for the dynamics of species' ranges? Answering this question has never been more important than today, in the light of rapid environmental changes. Surprisingly, the ecological and evolutionary dynamics of dispersal – which represent the driving forces behind range formation – have rarely been considered in this context. We here present a framework that closes this gap. Dispersal evolution may be responsible for highly complex and non‐trivial range dynamics. In order to understand these, and possibly provide projections of future range positions, it is crucial to take the ecological and evolutionary dynamics of dispersal into account.     

Identification of neuronal RNA targets of TDP-43-containing ribonucleoprotein complexes

TAR DNA-binding protein 43 (TDP-43) is associated with a spectrum of neurodegenerative diseases. Although TDP-43 resembles heterogeneous nuclear ribonucleoproteins, its RNA targets and physiological protein partners remain unknown. Here we identify RNA targets of TDP-43 from cortical neurons by RNA immunoprecipitation followed by deep sequencing (RIP-seq). The canonical TDP-43 binding site (TG)(n) is 55.1-fold enriched, and moreover, a variant with adenine in the middle, (TG)(n)TA(TG)(m), is highly abundant among reads in our TDP-43 RIP-seq library. TDP-43 RNA targets can be divided into three different groups: those primarily binding in introns, in exons, and across both introns and exons. TDP-43 RNA targets are particularly enriched for Gene Ontology terms related to synaptic function, RNA metabolism, and neuronal development. Furthermore, TDP-43 binds to a number of RNAs encoding for proteins implicated in neurodegeneration, including TDP-43 itself, FUS/TLS, progranulin, Tau, and ataxin 1 and -2. We also identify 25 proteins that co-purify with TDP-43 from rodent brain nuclear extracts. Prominent among them are nuclear proteins involved in pre-mRNA splicing and RNA stability and transport. Also notable are two neuron-enriched proteins, methyl CpG-binding protein 2 and polypyrimidine tract-binding protein 2 (PTBP2). A PTBP2 consensus RNA binding motif is enriched in the TDP-43 RIP-seq library, suggesting that PTBP2 may co-regulate TDP-43 RNA targets. This work thus reveals the protein and RNA components of the TDP-43-containing ribonucleoprotein complexes and provides a framework for understanding how dysregulation of TDP-43 in RNA metabolism contributes to neurodegeneration.     

Analysis of gene order data supports vertical inheritance of the leukotoxin operon and genome rearrangements in the 5' flanking region in genus <Emphasis Type="Italic">Mannheimia</Emphasis>

Background  

The Mannheimia subclades belong to the same bacterial genus, but have taken divergent paths toward their distinct lifestyles. For example, M. haemolytica + M. glucosida are potential pathogens of the respiratory tract in the mammalian suborder Ruminantia, whereas M. ruminalis, the supposed sister group, lives as a commensal in the ovine rumen. We have tested the hypothesis that vertical inheritance of the leukotoxin (lktCABD) operon has occurred from the last common ancestor of genus Mannheimia to any ancestor of the diverging subclades by exploring gene order data.     

Follistatin antagonizes transforming growth factor-beta3-induced epithelial-mesenchymal transition in vitro: implications for murine palatal development supported by microarray analysis

Abstract Epithelial–mesenchymal transition (EMT) is involved in normal embryonic development as well as in tumor progression and invasiveness. This process is also known to be a crucial step in palatogenesis during fusion of the bi-lateral palatal processes. Disruption of this step results in a cleft palate, which is among the most frequent birth defects in humans. A number of genes and encoded proteins have been shown to play a role in this developmental stage. The central role is attributed to the cytokine transforming growth factor-β3 (TGF-β3), which is expressed in the medial edge epithelium (MEE) already before the fusion process. The MEE covers the tips of the growing palatal shelves and eventually undergoes EMT or programmed cell death (apoptosis). TGF-β3 is described to induce EMT in embryonic palates. With regard to the early expression of this molecule before the fusion process, it is not well understood which mechanisms prevent the TGF-β3 producing epithelial cells from undergoing differentiation precociously. We used the murine palatal fusion to study the regulation of EMT. Specifically, we analyzed the MEE for the expression of known antagonists of TGF-β molecules using in situ hybridization and detected the gene coding for Follistatin to be co-expressed with TGF-β3. Further, we could show that Follistatin directly binds to TGF-β3 and that it completely blocks TGF-β3-induced EMT of the normal murine mammary gland (NMuMG) epithelial cell line in vitro . In addition, we analyzed the gene expression profile of NMuMG cells during TGF-β3-induced EMT by microarray hybridization, detecting strong changes in the expression of apoptosis-regulating genes.     

Determinants of the high-methionine trait in wild and exotic germplasm may have escaped selection during early cultivation of maize

The 18 kDa high-methionine δ-class zein gene from maize has been cloned, and its regulation, structure, and map position studied. These studies have shown that (i) zein genes may also contain tryptophan and lysine codons, (ii) the 18 kDa and the related 10 kDa zein gene are coordinately regulated, but their products accumulate to different levels in a genotype-dependent manner, (iii) the duplication of δ-zein genes probably involved unequal crossing over, (iv) no copy correction in either direction has occurred from teosinte to modern corn, and (v) the duplication of of the 18 kDa zein gene probably occurred before the tetraploidization of a progenitor chromosome. The work shows that important nutritional quality determinants like the high-methionine seed proteins are abundant in several exotic and wild corn varieties and low in most of the inbreds screened. The lack of a selectable phenotype for such quality traits during initial domestication and breeding of corn would have eliminated cis and trans regulatory determinants from the germplasm used in modern corn breeding. Examples of the high-methionine δ-class zeins shown here may be generally applicable in explaining the low nutritional quality of most present-day corn grown.     

Purification of acetyl-CoA: 17-O-deacetylvindoline 17-O-acetyltransferase from Catharanthus roseus leaves

The enzyme acetyl-CoA: 17-O-deacetylvindoline 17-O-acetyltransferase which terminates vindoline biosynthesis has been isolated from Catharanthus roseus leaves, further characterized and purified to homogeneity by three step column chromatography and subsequent preparative isoelectric focusing. Kinetic properties concerning the enzyme reaction are discussed. Five multiple forms of the acetyl-transferase could be observed, each consisting of two subunits. This enzyme is now the best characterized of the enzymes involved in vindoline biosynthesis.Abbreviations DTE dithiothreitol - EDTA ethylenediamine-tetraacetic acid - HEPES N-(2-hydroxyethyl)-piperazine-N-2-ethanesulfonic acid - IEF isoelectric focusing - KP_i potassium phosphate - M_r rel.molecular mass - PEG polyethylene glycol - SDS-PAGE sodium dodecylsulfate polyacrylamide gel electrophoresis - Tris 2-amino-2-(hydroxymethyl)-1,3-propandiol     

Deletion of complement factor H-related genes CFHR1 and CFHR3 is associated with atypical hemolytic uremic syndrome

Atypical hemolytic uremic syndrome (aHUS) is associated with defective complement regulation. Disease-associated mutations have been described in the genes encoding the complement regulators complement factor H, membrane cofactor protein, factor B, and factor I. In this study, we show in two independent cohorts of aHUS patients that deletion of two closely related genes, complement factor H-related 1 (CFHR1) and complement factor H-related 3 (CFHR3), increases the risk of aHUS. Amplification analysis and sequencing of genomic DNA of three affected individuals revealed a chromosomal deletion of approximately 84 kb in the RCA gene cluster, resulting in loss of the genes coding for CFHR1 and CFHR3, but leaving the genomic structure of factor H intact. The CFHR1 and CFHR3 genes are flanked by long homologous repeats with long interspersed nuclear elements (retrotransposons) and we suggest that nonallelic homologous recombination between these repeats results in the loss of the two genes. Impaired protection of erythrocytes from complement activation is observed in the serum of aHUS patients deficient in CFHR1 and CFHR3, thus suggesting a regulatory role for CFHR1 and CFHR3 in complement activation. The identification of CFHR1/CFHR3 deficiency in aHUS patients may lead to the design of new diagnostic approaches, such as enhanced testing for these genes.     

Sequence-Specific Size, Structure, and Stability of Tight Protein Knots

Approximately 1% of known protein structures display knotted configurations in their native fold, but the function of these configurations is not understood. It has been speculated that the entanglement may inhibit mechanical protein unfolding or transport, e.g., as in cellular threading or translocation processes through narrow biological pores. Protein knot manipulation, e.g., knot tightening and localization, has become possible in single-molecule experiments. Here, we investigate tight peptide knot (TPK) characteristics in detail by pulling selected 3₁ and 4₁-knotted peptides using all-atom molecular dynamics computer simulations. We find that the 3₁- and 4₁-TPK lengths are typically Δl ≈ 47± 4 Å and 69 ± 4 Å, respectively, for a wide range of tensions (0.1 nN ≲ F ≲ 1.5 nN). The 4₁-knot length is in agreement with recent atomic force microscopy pulling experiments. Calculated TPK radii of gyration point to a pore diameter of ∼20 Å, below which a translocated knotted protein might get stuck. TPK characteristics, however, may be sequence-specific: we find a different size and structural behavior in polyglycines, and, strikingly, a strong hydrogen bonding and water trapping capability of hydrophobic TPKs. Water capture and release is found to be controllable by the tightening force in a few cases. These mechanisms result in a sequence-specific “locking” and metastability of TPKs, which might lead to a blocking of knotted peptide transport at designated sequence positions. We observe that macroscopic tight 4₁-knot structures are reproduced microscopically (“figure of eight” versus the “pretzel”) and can be tuned by sequence, in contrast to mathematical predictions. Our findings may explain a function of knots in native proteins, challenge previous studies on macromolecular knots, and prove useful in bio- and nanotechnology.