Towards a ‘Sea‐Level Sensitive’ dynamic model: impact of island ontogeny and glacio‐eustasy on global patterns of marine island biogeography

A synthetic model is presented to enlarge the evolutionary framework of the General Dynamic Model (GDM) and the Glacial Sensitive Model (GSM) of oceanic island biogeography from the terrestrial to the marine realm. The proposed ‘Sea‐Level Sensitive’ dynamic model (SLS) of marine island biogeography integrates historical and ecological biogeography with patterns of glacio‐eustasy, merging concepts from areas as diverse as taxonomy, biogeography, marine biology, volcanology, sedimentology, stratigraphy, palaeontology, geochronology and geomorphology. Fundamental to the SLS model is the dynamic variation of the littoral area of volcanic oceanic islands (defined as the area between the intertidal and the 50‐m isobath) in response to sea‐level oscillations driven by glacial–interglacial cycles. The following questions are considered by means of this revision: (i) what was the impact of (global) glacio‐eustatic sea‐level oscillations, particularly those of the Pleistocene glacial–interglacial episodes, on the littoral marine fauna and flora of volcanic oceanic islands? (ii) What are the main factors that explain the present littoral marine biodiversity on volcanic oceanic islands? (iii) How can differences in historical and ecological biogeography be reconciled, from a marine point of view? These questions are addressed by compiling the bathymetry of 11 Atlantic archipelagos/islands to obtain quantitative data regarding changes in the littoral area based on Pleistocene sea‐level oscillations, from 150 thousand years ago (ka) to the present. Within the framework of a model sensitive to changing sea levels, we discuss the principal factors affecting the geographical range of marine species; the relationships between modes of larval development, dispersal strategies and geographical range; the relationships between times of speciation, modes of larval development, ecological zonation and geographical range; the influence of sea‐surface temperatures and latitude on littoral marine species diversity; the effect of eustatic sea‐level changes and their impact on the littoral marine biota; island marine species–area relationships; and finally, the physical effects of island ontogeny and its associated submarine topography and marine substrate on littoral biota. Based on the SLS dynamic model, we offer a number of predictions for tropical, subtropical and temperate volcanic oceanic islands on how rates of immigration, colonization, in‐situ speciation, local disappearance, and extinction interact and affect the marine biodiversity around islands during glacials and interglacials, thus allowing future testing of the theory.     

Recycling of a glycosylphosphatidylinositol-anchored heparan sulphate proteoglycan (glypican) in skin fibroblasts

We have used suramin and brefeldin A to investigate the natureof a heparan sulphate proteoglycan that appears to recycle fromthe cell surface to intracellular compartments which synthesizenew heparan sulphate chains. Suramin, which would block internalizationand deglycanation of a putative recycling cell surface proteoglycan,markedly increases the yield of a membrane-bound proteoglycanwith a core protein of 60–70 kDa and unusually long heparansulphate side chains. When transport of newly made core proteinsto their Golgi sites for glycosaminoglycan assembly is blocked,by using brefeldin A, [³H]glucosamine and [³⁵S]sulphate incorporationinto cell surface-bound heparan sulphate proteoglycan can stilltake place. After chemical biotinylation of cell surface proteinsin brefeldin A-treated cells, followed by metabolic [³⁵S]sulphationin the presence of the same drug, biotin-tagged [³⁵S]proteoglycancan be demonstrated, indicating the presence of recycling proteoglycanspecies. By prelabelling cells with [³H]leucine or [³H]inositolin the presence of suramin, followed by chase labelling with[³⁵S]sulphate in the presence of brefeldin A, a ³H- and ³⁵S-labelled,hydrophobic heparan sulphate proteoglycan with a core proteinof 60–65 kDa is obtained. The proteoglycan loses its hydrophobicitywhen glucosamineinositol bonds are cleaved, indicating thatit is membrane bound via a glycosylphosphatidylinositol anchor.However, treatment with phosphatidylinositol-specific phospholipaseC has no effect, suggesting that the inositol moiety may beacylated. We propose that a portion of the lipid-anchored proteoglycanglypican is internalized, recycled via the Golgi, where heparansulphate chains are added, and finally re-deposited at the cellsurface. glycosylphosphatidylinositol-anchored glypican heparan sulphate proteoglycan recycling     

Repair of the mutagenic DNA oxidation product, 5-formyluracil

The oxidation of the thymine methyl group can generate 5-formyluracil (FoU). Template FoU residues are known to miscode, generating base substitution mutations. The repair of the FoU lesion is therefore important in minimizing mutations induced by DNA oxidation. We have studied the repair of FoU in synthetic oligonucleotides when paired with A and G. In E. coli cell extract, the repair of FoU is four orders of magnitude lower than the repair of U and is similar for both FoU:A and FoU:G base pairs. In HeLa nuclear extract, the repair of FoU:A is similarly four orders of magnitude lower than the repair of uracil, although the FoU:G lesion is repaired 10 times more efficiently than FoU:A. The FoU:G lesion is shown to be repaired by E. coli mismatch uracil DNA glycosylase (Mug), thermophile mismatch thymine DNA glycosylase (Tdg), mouse mismatch thymine DNA glycosylase (mTDG) and human methyl-CpG-binding thymine DNA glycosylase (MBD4), whereas the FoU:A lesion is repaired only by Mug and mTDG. The repair of FoU relative to the other pyrimidines examined here in human cell extract differs from the substrate preferences of the known glycosylases, suggesting that additional, and as yet unidentified glycosylases exist in human cells to repair the FoU lesion. Indeed, as observed in HeLa nuclear extract, the repair of mispaired FoU derived from misincorporation of dGMP across from template FoU could promote rather than minimize mutagenesis. The pathways by which this important lesion is repaired in human cells are as yet unexplained, and are likely to be complex.     

Identification of the centromeres of Leishmania major: revealing the hidden pieces

Leishmania affects millions of people worldwide. Its genome undergoes constitutive mosaic aneuploidy, a type of genomic plasticity that may serve as an adaptive strategy to survive distinct host environments. We previously found high rates of asymmetric chromosome allotments during mitosis that lead to the generation of such ploidy. However, the underlying molecular events remain elusive. Centromeres and kinetochores most likely play a key role in this process, yet their identification has failed using classical methods. Our analysis of the unconventional kinetochore complex recently discovered in Trypanosoma brucei (KKTs) leads to the identification of a Leishmania KKT gene candidate (LmKKT1). The GFP‐tagged LmKKT1 displays “kinetochore‐like” dynamics of intranuclear localization throughout the cell cycle. By ChIP‐Seq assay, one major peak per chromosome is revealed, covering a region of 4 ±2 kb. We find two largely conserved motifs mapping to 14 of 36 chromosomes while a higher density of retroposons are observed in 27 of 36 centromeres. The identification of centromeres and of a kinetochore component of Leishmania chromosomes opens avenues to explore their role in mosaic aneuploidy.     

COBRAMM 2.0 — A software interface for tailoring molecular electronic structure calculations and running nanoscale (QM/MM) simulations

We present a new version of the simulation software COBRAMM, a program package interfacing widely known commercial and academic software for molecular modeling. It allows a problem-driven tailoring of computational chemistry simulations with effortless ground and excited-state electronic structure computations. Calculations can be executed within a pure QM or combined quantum mechanical/molecular mechanical (QM/MM) framework, bridging from the atomistic to the nanoscale. The user can perform all necessary steps to simulate ground state and photoreactions in vacuum, complex biopolymer, or solvent environments. Starting from ground-state optimization, reaction path computations, initial conditions sampling, spectroscopy simulation, and photodynamics with deactivation events, COBRAMM is designed to assist in characterization and analysis of complex molecular materials and their properties. Interpretation of recorded spectra range from steady-state to time-resolved measurements. Various tools help the user to set up the system of interest and analyze the results.     

c-Jun N-Terminal Kinase Phosphorylation of MARCKSL1 Determines Actin Stability and Migration in Neurons and in Cancer Cells

Cell migration is a fundamental biological function, critical during development and regeneration, whereas deregulated migration underlies neurological birth defects and cancer metastasis. MARCKS-like protein 1 (MARCKSL1) is widely expressed in nervous tissue, where, like Jun N-terminal protein kinase (JNK), it is required for neural tube formation, though the mechanism is unknown. Here we show that MARCKSL1 is directly phosphorylated by JNK on C-terminal residues (S120, T148, and T183). This phosphorylation enables MARCKSL1 to bundle and stabilize F-actin, increase filopodium numbers and dynamics, and retard migration in neurons. Conversely, when MARCKSL1 phosphorylation is inhibited, actin mobility increases and filopodium formation is compromised whereas lamellipodium formation is enhanced, as is cell migration. We find that MARCKSL1 mRNA is upregulated in a broad range of cancer types and that MARCKSL1 protein is strongly induced in primary prostate carcinomas. Gene knockdown in prostate cancer cells or in neurons reveals a critical role for MARCKSL1 in migration that is dependent on the phosphorylation state; phosphomimetic MARCKSL1 (MARCKSL1(S120D,T148D,T183D)) inhibits whereas dephospho-MARCKSL1(S120A,T148A,T183A) induces migration. In summary, these data show that JNK phosphorylation of MARCKSL1 regulates actin homeostasis, filopodium and lamellipodium formation, and neuronal migration under physiological conditions and that, when ectopically expressed in prostate cancer cells, MARCKSL1 again determines cell movement.     

Presence of triploids among oak species

BACKGROUND AND AIMS: Polyploids, organisms that have multiple sets of chromosomes, are common in certain plant and animal taxa. However, there are only a few reports of intraspecific ploidy variation within the genus Quercus. The aim of the study was to investigate the suspected ploidy level of two oaks that have unusual microsatellite banding patterns. METHODS: Polyploidy was investigated by using microsatellite analysis, stomata length measurements and nuclear DNA content estimation by flow cytometry. KEY RESULTS: Each putative triploid tree has patterns of microsatellite variation unexpected for diploid genomes, with up to three alleles at some loci, significantly longer stomata and 1.5 times more DNA per nucleus compared with diploids. CONCLUSIONS: To our knowledge, this report contains the first evidence for triploidy in Q. petraea and confirmation of this phenomenon in Q. robur. Regardless of the positive or negative aspects of the presence of triploid oaks in forest stands, it is of value to be able to screen for them. This study demonstrates that nuclear microsatellites and estimation of DNA content by flow cytometry can readily be used for this purpose.     

Cytokine-inducing lipoteichoic acids of the allergy-protective bacterium Lactococcus lactis G121 do not activate via Toll-like receptor 2

It was established in a mouse model that the cowshed Gram-positive bacterium Lactococcus lactis G121 modulates the immune system resulting in allergy protection. However, the molecules and mechanisms involved in this process have not been elucidated yet. Lipoteichoic acids (LTAs) represent one major cell envelope component of Gram-positive bacteria that is considered a pathogen-associated molecular pattern. In the investigations presented here, the isolation as well as the structural and functional analyses of the LTA of L. lactis G121 were performed. Extraction with butan-1-ol and purification by hydrophobic interaction chromatography yielded pure LTA. Structural investigations included chemical analytical methods, nuclear magnetic resonance spectroscopy and high-resolution electrospray ionization Fourier-transformed ion cyclotron mass spectrometry. LTA comprised a heterogeneous mixture of molecules composed of a 1,3-linked poly(glycerol phosphate) backbone which was randomly substituted at C-2 by D-alanine and α-D-galactopyranose. The lipid anchor constituents were kojibiose linked to a heterogeneous diglyceride comprising in total six different fatty acid compositions. This LTA preparation possesses Toll-like receptor 2- (TLR2) and TLR4-independent cytokine-inducing activities in human mononuclear cells.