ProtoMD: A Prototyping Toolkit for Multiscale Molecular Dynamics

ProtoMD is a toolkit that facilitates the development of algorithms for multiscale molecular dynamics (MD) simulations. It is designed for multiscale methods which capture the dynamic transfer of information across multiple spatial scales, such as the atomic to the mesoscopic scale, via coevolving microscopic and coarse-grained (CG) variables. ProtoMD can be also be used to calibrate parameters needed in traditional CG-MD methods. The toolkit integrates `GROMACS wrapper' to initiate MD simulations, and `MDAnalysis' to analyze and manipulate trajectory files. It facilitates experimentation with a spectrum of coarse-grained variables, prototyping rare events (such as chemical reactions), or simulating nanocharacterization experiments such as terahertz spectroscopy, AFM, nanopore, and time-of-flight mass spectroscopy. ProtoMD is written in python and is freely available under the GNU General Public License from github.com/CTCNano/proto_md

Molecular analysis of ivy cells of the hippocampal CA1 stratum radiatum using spectral identification of immunofluorophores

Neuronal nitric oxide synthase-expressing (nNOS+) GABAergic interneurons are common in hippocampal stratum (str.) radiatum. However, these cells are less well characterized than nNOS+ ivy cells in str. pyramidale or neurogliaform cells (NGC) in str. lacunosum-moleculare. Here we have studied the laminar distribution of the axons and dendrites, and the immunoreactivity of these neurons recorded in rat hippocampal slices. We have used spectral analysis of antibody- or streptavidin-conjugated fluorophores to improve recognition of genuine signals in reactions for molecules such as nNOS and neuropeptide-Y (NPY). We found that most nNOS+ cells with soma in the CA1 area str. radiatum exhibit characteristic properties of ivy cells, and were positive for NPY and negative for reelin. However, laminar distributions of their neurites differ from original characterization of ivy cells with the soma in or close to str. pyramidale. Both their dendrites and axon are mainly in str. radiatum and to a lesser extent in str. oriens, and in addition often extend to str. lacunosum-moleculare. We conclude that ivy cells in str. radiatum may predominantly be feedforward inhibitory interneurons in the CA1 area, and their axonal output delivering GABA, NPY, and NO can influence both the entorhinal cortex innervated and the CA3 innervated zones pre- and post-synaptically. Spectral analysis of fluorophores provides an objective algorithm to analyze signals in immunoreactions for neurochemical markers

Minimizing the overheads of dependent {AND}-parallelism

Parallel implementations of programming languages need to control synchronization overheads. Synchronization is essential for ensuring the correctness of parallel code, yet it adds overheads that aren\u27t present in sequential programs. This is an important problem for parallel logic programming systems, because almost every action in such programs requires accessing variables, and the traditional approach of adding synchronization code to all such accesses is so prohibitively expensive that a parallel version of the program may run more slowly on four processors than a sequential version would run on one processor. We present a program transformation for implementing dependent AND-parallelism in logic programming languages that uses mode information to add synchronization code only to the variable accesses that actually need it

Role of ionotropic glutamate receptors in long-term potentiation in rat hippocampal CA1 oriens-lacunosum moleculare interneurons

Some interneurons of the hippocampus exhibit NMDA receptor-independent long-term potentiation (LTP) that is induced by presynaptic glutamate release when the postsynaptic membrane potential is hyperpolarized. This "anti-Hebbian" form of LTP is prevented by postsynaptic depolarization or by blocking AMPA and kainate receptors. Although both AMPA and kainate receptors are expressed in hippocampal interneurons, their relative roles in anti-Hebbian LTP are not known. Because interneuron diversity potentially conceals simple rules underlying different forms of plasticity, we focus on glutamatergic synapses onto a subset of interneurons with dendrites in stratum oriens and a main ascending axon that projects to stratum lacunosum moleculare, the oriens-lacunosum moleculare (O-LM) cells. We show that anti-Hebbian LTP in O-LM interneurons has consistent induction and expression properties, and is prevented by selective inhibition of AMPA receptors. The majority of the ionotropic glutamatergic synaptic current in these cells is mediated by inwardly rectifying Ca(2+)-permeable AMPA receptors. Although GluR5-containing kainate receptors contribute to synaptic currents at high stimulus frequency, they are not required for LTP induction. Glutamatergic synapses on O-LM cells thus behave in a homogeneous manner and exhibit LTP dependent on Ca(2+)-permeable AMPA receptors

Early and selective localization of tau filaments to glutamatergic subcellular domains within the human anterodorsal thalamus

Widespread cortical accumulation of misfolded pathological tau proteins (ptau) in the form of paired helical filaments is a major hallmark of Alzheimer’s disease. Subcellular localization of ptau at various stages of disease progression is likely to be informative of the cellular mechanisms involving its spread. Here, we found that the density of ptau within several distinct rostral thalamic nuclei in post-mortem human tissue (n = 25 cases) increased with the disease stage, with the anterodorsal nucleus (ADn) consistently being the most affected. In the ADn, ptau-positive elements were present already in the pre-cortical (Braak 0) stage. Tau pathology preferentially affected the calretinin-expressing subpopulation of glutamatergic neurons in the ADn. At the subcellular level, we detected ptau immunoreactivity in ADn cell bodies, dendrites, and in a specialized type of presynaptic terminal that expresses vesicular glutamate transporter 2 (vGLUT2) and likely originates from the mammillary body. The ptau-containing terminals displayed signs of degeneration, including endosomal/lysosomal organelles. In contrast, corticothalamic axon terminals lacked ptau. The data demonstrate the involvement of a specific cell population in ADn at the onset of the disease. The presence of ptau in subcortical glutamatergic presynaptic terminals supports hypotheses about the transsynaptic spread of tau selectively affecting specialized axonal pathways

Review of existing information on the interrelations between soil and climate change. (ClimSoil). Final report

Carbon stock in EU soils – The soil carbon stocks in the EU27 are around 75 billion tonnes of carbon (C); of this stock around 50% is located in Sweden, Finland and the United Kingdom (because of the vast area of peatlands in these countries) and approximately 20% is in peatlands, mainly in countries in the northern part of Europe. The rest is in mineral soils, again the higher amount being in northern Europe. 2. Soils sink or source for CO2 in the EU – Both uptake of carbon dioxide (CO2) through photosynthesis and plant growth and loss of CO2 through decomposition of organic matter from terrestrial ecosystems are significant fluxes in Europe. Yet, the net terrestrial carbon fluxes are typically 5-10 times smaller relative to the emissions from use of fossil fuel of 4000 Mt CO2 per year. 3. Peat and organic soils - The largest emissions of CO2 from soils are resulting from land use change and especially drainage of organic soils and amount to 20-40 tonnes of CO2 per hectare per year. The most effective option to manage soil carbon in order to mitigate climate change is to preserve existing stocks in soils, and especially the large stocks in peat and other soils with a high content of organic matter. 4. Land use and soil carbon – Land use and land use change significantly affects soil carbon stocks. On average, soils in Europe are most likely to be accumulating carbon on a net basis with a sink for carbon in soils under grassland and forest (from 0 - 100 billion tonnes of carbon per year) and a smaller source for carbon from soils under arable land (from 10 - 40 billion tonnes of carbon per year). Soil carbon losses occur when grasslands, managed forest lands or native ecosystems are converted to croplands and vice versa carbon stocks increase, albeit it slower, following conversion of cropland. 5. Soil management and soil carbon – Soil management has a large impact on soil carbon. Measures directed towards effective management of soil carbon are available and identified, and many of these are feasible and relatively inexpensive to implement. Management for lower nitrogen (N) emissions and lower C emissions is a useful approach to prevent trade off and swapping of emissions between the greenhouse gases CO2, methane (CH4) and nitrous oxide (N2O). 6. Carbon sequestration – Even though effective in reducing or slowing the build up of CO2 in the atmosphere, soil carbon sequestration is surely no ‘golden bullet’ alone to fight climate change due to the limited magnitude of its effect and its potential reversibility; it could, nevertheless, play an important role in climate mitigation alongside other measures, especially because of its immediate availability and relative low cost for 'buying' us time. 7. Effects of climate change on soil carbon pools – Climate change is expected to have an impact on soil carbon in the longer term, but far less an impact than does land use change, land use and land management. We have not found strong and clear evidence for either overall and combined positive of negative impact of climate change (atmospheric CO2, temperature, precipitation) on soil carbon stocks. Due to the relatively large gross exchange of CO2 between atmosphere and soils and the significant stocks of carbon in soils, relatively small changes in these large and opposing fluxes of CO2, i.e. as result of land use (change), land management and climate change, may have significant impact on our climate and on soil quality. 8. Monitoring systems for changes in soil carbon – Currently, monitoring and knowledge on land use and land use change in EU27 is inadequate for accurate calculation of changes in soil carbon contents. Systematic and harmonized monitoring across EU27 and across relevant land uses would allow for adequate representation of changes in soil carbon in reporting emissions from soils and sequestration in soils to the UNFCCC. 9. EU policies and soil carbon – Environmental requirements under the Cross Compliance requirement of CAP is an instrument that may be used to maintain SOC. Neither measures under UNFCCC nor those mentioned in the proposed Soil Framework Directive are expected to adversely impact soil C. EU policy on renewable energy is not necessarily a guarantee for appropriate (soil) carbon management

An Arp2/3 Nucleated F-Actin Shell Fragments Nuclear Membranes at Nuclear Envelope Breakdown in Starfish Oocytes

Animal cells disassemble and reassemble their nuclear envelopes (NEs) upon each division. Nuclear envelope breakdown (NEBD) serves as a major regulatory mechanism by which mixing of cytoplasmic and nuclear compartments drives the complete reorganization of cellular architecture, committing the cell for division. Breakdown is initiated by phosphorylation-driven partial disassembly of the nuclear pore complexes (NPCs), increasing their permeability but leaving the overall NE structure intact. Subsequently, the NE is rapidly broken into membrane fragments, defining the transition from prophase to prometaphase and resulting in complete mixing of cyto- and nucleoplasm. However, the mechanism underlying this rapid NE fragmentation remains largely unknown. Here, we show that NE fragmentation during NEBD in starfish oocytes is driven by an Arp2/3 complex-nucleated F-actin “shell” that transiently polymerizes on the inner surface of the NE. Blocking the formation of this F-actin shell prevents membrane fragmentation and delays entry of large cytoplasmic molecules into the nucleus. We observe spike-like protrusions extending from the F-actin shell that appear to “pierce” the NE during the fragmentation process. Finally, we show that NE fragmentation is essential for successful reproduction, because blocking this process in meiosis leads to formation of aneuploid eggs.MIT Faculty Start-up FundNational Science Foundation (U.S.). Graduate Research Fellowshi