Biological processes and links to the physics

Analysis of the temporal and spatial variability of biological processes and identification of the main variables that drive the dynamic regime of marine ecosystems is complex. Correlation between physical variables and long-term changes in ecosystems has routinely been identified, but the specific mechanisms involved remain often unclear. Reasons for this could be various: the ecosystem can be very sensitive to the seasonal timing of the anomalous physical forcing; the ecosystem can be contemporaneously influenced by many physical variables and the ecosystem can generate intrinsic variability on climate time scales. Marine ecosystems are influenced by a variety of physical factors, e.g., light, temperature, transport, turbulence. Temperature has a fundamental forcing function in biology, with direct influences on rate processes of organisms and on the distribution of mobile species that have preferred temperature ranges. Light and transport also affect the physiology and distribution of marine organisms. Small-scale turbulence determines encounter between larval fish and their prey and additionally influences the probability of successful pursuit and ingestion. The impact of physical forcing variations on biological processes is studied through long-term observations, process studies, laboratory experiments, retrospective analysis of existing data sets and modelling. This manuscript reviews the diversity of physical influences on biological processes, marine organisms and ecosystems and their variety of responses to physical forcing with special emphasis on the dynamics of zooplankton and fish stocks

Generation of anti-TLR2 intrabody mediating inhibition of macrophage surface TLR2 expression and TLR2-driven cell activation

<p>Abstract</p> <p>Background</p> <p>Toll-like receptor (TLR) 2 is a component of the innate immune system and senses specific pathogen associated molecular patterns (PAMPs) of both microbial and viral origin. Cell activation via TLR2 and other pattern recognition receptors (PRRs) contributes to sepsis pathology and chronic inflammation both relying on overamplification of an immune response. Intracellular antibodies expressed and retained inside the endoplasmatic reticulum (ER-intrabodies) are applied to block translocation of secreted and cell surface molecules from the ER to the cell surface resulting in functional inhibition of the target protein. Here we describe generation and application of a functional anti-TLR2 ER intrabody (αT2ib) which was generated from an antagonistic monoclonal antibody (mAb) towards human and murine TLR2 (T2.5) to inhibit the function of TLR2. αT2ib is a scFv fragment comprising the variable domain of the heavy chain and the variable domain of the light chain of mAb T2.5 linked together by a synthetic (Gly₄Ser)₃amino acid sequence.</p> <p>Results</p> <p>Coexpression of αT2ib and mouse TLR2 in HEK293 cells led to efficient retention and accumulation of TLR2 inside the ER compartment. Co-immunoprecipitation of human TLR2 with αT2ib indicated interaction of αT2ib with its cognate antigen within cells. αT2ib inhibited NF-κB driven reporter gene activation via TLR2 but not through TLR3, TLR4, or TLR9 if coexpressed in HEK293 cells. Co-transfection of human TLR2 with increasing amounts of the expression plasmid encoding αT2ib into HEK293 cells demonstrated high efficiency of the TLR2-αT2ib interaction. The αT2ib open reading frame was integrated into an adenoviral cosmid vector for production of recombinant adenovirus (AdV)-αT2ib. Transduction with AdVαT2ib specifically inhibited TLR2 surface expression of murine RAW264.7 and primary macrophages derived from bone marrow (BMM). Furthermore, TLR2 activation dependent TNFα mRNA accumulation, as well as TNFα translation and release by macrophages were largely abrogated upon transduction of αT2ib. αT2ib was expressed in BMM and splenocytes over 6 days upon systemic infection with AdVαT2ib. Systemic transduction applying AdVαT2ib rendered immune cells largely non-responsive to tripalmitoyl-peptide challenge. Our results show persistent paralysis of TLR2 activity and thus inhibition of immune activation.</p> <p>Conclusion</p> <p>The generated anti-TLR2 scFv intrabody inhibits specifically and very efficiently TLR2 ligand-driven cell activation <it>in vitro </it>and <it>ex vivo</it>. This indicates a therapeutic potential of αT2ib in microbial or viral infections.</p

Evaluating the suitability of coupled biophysical models for fishery management

The potential role of coupled biophysical models in enhancing the conservation, management, and recovery of fish stocks is assessed, with emphasis on anchovy, cod, herring, and sprat in European waters. The assessment indicates that coupled biophysical models are currently capable of simulating transport patterns, along with temperature and prey fields within marine ecosystems; they therefore provide insight into the variability of early-life-stage dynamics and connectivity within stocks. Moreover, the influence of environmental variability on potential recruitment success may be discerned from model hindcasts. Based on case studies, biophysical modelling results are shown to be capable of shedding light on whether stock management frameworks need re-evaluation. Hence, key modelling products were identified that will contribute to the development of viable stock recovery plans and management strategies. The study also suggests that approaches combining observation, process knowledge, and numerical modelling could be a promising way forward in understanding and simulating the dynamics of marine fish populations

Focused ion beam-scanning electron microscopy links pathological myelin outfoldings to axonal changes in mice lacking Plp1 or Mag

Healthy myelin sheaths consist of multiple compacted membrane layers closely encasing the underlying axon. The ultrastructure of CNS myelin requires specialized structural myelin proteins, including the transmembrane-tetraspan proteolipid protein (PLP) and the Ig-CAM myelin-associated glycoprotein (MAG). To better understand their functional relevance, we asked to what extent the axon/myelin-units display similar morphological changes if PLP or MAG are lacking. We thus used focused ion beam-scanning electron microscopy (FIB-SEM) to re-investigate axon/myelin-units side-by-side in Plp- and Mag-null mutant mice. By three-dimensional reconstruction and morphometric analyses, pathological myelin outfoldings extend up to 10 μm longitudinally along myelinated axons in both models. More than half of all assessed outfoldings emerge from internodal myelin. Unexpectedly, three-dimensional reconstructions demonstrated that both models displayed complex axonal pathology underneath the myelin outfoldings, including axonal sprouting. Axonal anastomosing was additionally observed in Plp-null mutant mice. Importantly, normal-appearing axon/myelin-units displayed significantly increased axonal diameters in both models according to quantitative assessment of electron micrographs. These results imply that healthy CNS myelin sheaths facilitate normal axonal diameters and shape, a function that is impaired when structural myelin proteins PLP or MAG are lacking

Contrasting properties of particle-particle and hole-hole excitations in ²⁰⁶Tl and ²¹⁰Bi nuclei

A complete-spectroscopy investigation of low-lying, low-spin states in the one-proton-hole and one-neutron-hole nucleus 206Tl has been performed by using thermal neutron capture and γ-coincidence technique with the FIPPS Ge array at ILL Grenoble. The new experimental results, together with data for the one-proton-particle and one-neutron-particle nucleus 210Bi (taken from a previous study done at ILL in the EXILL campaign), allowed for an extensive comparison with predictions of shell-model calculations performed with realistic interactions. No phenomenological adjustments were introduced in the calculations. In 210Bi, state energies, transition multipolarities and decay branchings agree well with theory for the three well separated multiplets of states which dominate the low-lying excitations. On the contrary, in 206Tl significant discrepancies are observed: in the same energy region, six multiplets were identified, with a significant mixing among them being predicted, as a consequence of the smaller energy separation between the active orbitals. The discrepancies in 206Tl are attributed to the larger uncertainties in the determination of the off-diagonal matrix elements of the realistic shell-model interaction with respect to the calculated diagonal matrix elements, the only ones playing a major role in the case of 210Bi. The work points to the need of more advanced approaches in the construction of the realistic interactions

The (n, gamma) campaigns at EXILL

At the PF1B cold neutron beam line at the Institut Laue Langevin, the EXILL array consisting of EXOGAM, GASP and ILL-Clover detectors was used to perform (n, gamma) measurements at very high coincidence rates. About ten different reactions were measured in autumn 2012 using a highly collimated cold neutron beam. In spring 2013, the EXOGAM array was combined with 16 LaBr3(Ce) scintillators in the EXILL&FATIMA campaign for the measurement of lifetimes using the generalised centroid difference method. We report on the properties of the set-ups and present first results from both campaigns