Experience-dependent structural plasticity at pre- and postsynaptic sites of layer 2/3 cells in developing visual cortex

The developing brain can respond quickly to altered sensory experience by circuit reorganization. During a critical period in early life, neurons in the primary visual cortex rapidly lose responsiveness to an occluded eye and come to respond better to the open eye. While physiological and some of the molecular mechanisms of this process have been characterized, its structural basis, except for the well-known changes in the thalamocortical projection, remains obscure. To elucidate the relationship between synaptic remodeling and functional changes during this experience-dependent process, we used 2-photon microscopy to image synaptic structures of sparsely labeled layer 2/3 neurons in the binocular zone of mouse primary visual cortex. Anatomical changes at presynaptic and postsynaptic sites in mice undergoing monocular visual deprivation (MD) were compared to those in control mice with normal visual experience. We found that postsynaptic spines remodeled quickly in response to MD, with neurons more strongly dominated by the deprived eye losing more spines. These postsynaptic changes parallel changes in visual responses during MD and their recovery after restoration of binocular vision. In control animals with normal visual experience, the formation of presynaptic boutons increased during the critical period and then declined. MD affected bouton formation, but with a delay, blocking it after 3 d. These findings reveal intracortical anatomical changes in cellular layers of the cortex that can account for rapid activity-dependent plasticity

Ciliary assessment in bronchiectasis: is there a clinico-pathological correlation?

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Dynamic Covalent Synthesis of Crystalline Porous Graphitic Frameworks

Porous graphitic framework (PGF) is a two-dimensional (2D) material that has emerging energy applications. An archetype contains stacked 2D layers, the structure of which features a fully annulated aromatic skeleton with embedded heteroatoms and periodic pores. Due to the lack of a rational approach in establishing in-plane order under mild synthetic conditions, the structural integrity of PGF has remained elusive and ultimately limited its material performance. Here, we report the discovery of the unusual dynamic character of the C=N bonds in the aromatic pyrazine ring system under basic aqueous conditions, which enables the successful synthesis of a crystalline porous nitrogenous graphitic framework with remarkable in-plane order, as evidenced by powder X-ray diffraction studies and direct visualization using high-resolution transmission electron microscopy. The crystalline framework displays superior performance as a cathode material for lithium-ion batteries, outperforming the amorphous counterparts in terms of capacity and cycle stability. Insertion of well-defined, evenly spaced nanoscale pores into the two-dimensional (2D) layers of graphene invokes exciting properties due to the modulation of its electronic band gaps and surface functionalities. A bottom-up synthesis approach to such porous graphitic frameworks (PGFs) is appealing but also remains a great challenge. The current methods of building covalent organic frameworks rely on a small collection of thermodynamically reversible reactions. Such reactions are, however, inadequate in generating a fully annulated aromatic skeleton in PGFs. With the discovery of dynamic pyrazine formation, we succeeded in applying this linking chemistry to obtain a crystalline PGF material, which has displayed high electrical conductivity and remarkable performance as a cathode material for lithium-ion batteries. We envision that the demonstrated success will open the door to a wide array of fully annulated 2D porous frameworks, which hold immense potential for clean energy applications. We report the unusual dynamic characteristics of the C=N bonds in the pyrazine ring promoted under basic aqueous conditions, which enables the successful synthesis of two-dimensional porous graphitic frameworks (PGFs) featuring fully annulated aromatic skeletons and periodic pores. The PGF displayed high electrical conductivity and remarkable performance as a cathode material for lithium-ion batteries, far outperforming the amorphous counterparts in terms of capacity and cycle stability

Protective effects of hydrogen enriched saline on liver ischemia reperfusion injury by reducing oxidative stress and HMGB1 release

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Annotating patient clinical records with syntactic chunks and named entities: the Harvey corpus

The free text notes typed by physicians during patient consultations contain valuable information for the study of disease and treatment. These notes are difficult to process by existing natural language analysis tools since they are highly telegraphic (omitting many words), and contain many spelling mistakes, inconsistencies in punctuation, and non-standard word order. To support information extraction and classification tasks over such text, we describe a de-identified corpus of free text notes, a shallow syntactic and named entity annotation scheme for this kind of text, and an approach to training domain specialists with no linguistic background to annotate the text. Finally, we present a statistical chunking system for such clinical text with a stable learning rate and good accuracy, indicating that the manual annotation is consistent and that the annotation scheme is tractable for machine learning

Bisphosphonate drugs have actions in the lung and inhibit the mevalonate pathway in alveolar macrophages.

Bisphosphonates drugs target the skeleton and are used globally for the treatment of common bone disorders. Nitrogen-containing bisphosphonates act by inhibiting the mevalonate pathway in bone-resorbing osteoclasts but, surprisingly, also appear to reduce the risk of death from pneumonia. We overturn the long-held belief that these drugs act only in the skeleton and show that a fluorescently labelled bisphosphonate is internalised by alveolar macrophages and large peritoneal macrophages in vivo. Furthermore, a single dose of a nitrogen-containing bisphosphonate (zoledronic acid) in mice was sufficient to inhibit the mevalonate pathway in tissue-resident macrophages, causing the build-up of a mevalonate metabolite and preventing protein prenylation. Importantly, one dose of bisphosphonate enhanced the immune response to bacterial endotoxin in the lung and increased the level of cytokines and chemokines in bronchoalveolar fluid. These studies suggest that bisphosphonates, as well as preventing bone loss, may boost immune responses to infection in the lung and provide a mechanistic basis to fully examine the potential of bisphosphonates to help combat respiratory infections that cause pneumonia

Direct observation of local K variation and its correlation to electronic inhomogeneity in (Ba1-xKx)Fe2As2 Pnictide

Local fluctuations in the distribution of dopant atoms are a suspected cause of nanoscale electronic disorder or phase separation observed within the pnictide superconductors. Atom probe tomography results present the first direct observations of dopant nano-clustering in a K-doped 122-phase pnictides. First-principles calculations suggest the coexistence of static magnetism and superconductivity on a lattice parameter length scale over a large range of doping concentrations. Collectively, our results provide evidence for a mixed scenario of phase coexistence and phase separation originating from variation of dopant atom experiments distroibutions.Comment: 4 pages, 4 figures and 1 table, accepted by Physical Review Letter 201

Colossal magnetocapacitance and scale-invariant dielectric response in phase-separated manganites

Thin films of strongly-correlated electron materials (SCEM) are often grown epitaxially on planar substrates and typically have anisotropic properties that are usually not captured by edge-mounted four-terminal electrical measurements, which are primarily sensitive to in-plane conduction paths. Accordingly, the correlated interactions in the out-of-plane (perpendicular) direction cannot be measured but only inferred. We address this shortcoming and show here an experimental technique in which the SCEM under study, in our case a 600 Angstrom-thick (La1-yPry)0.67Ca0.33MnO3 (LPCMO) film, serves as the base electrode in a metal-insulator-metal (MIM) trilayer capacitor structure. This unconventional arrangement allows for simultaneous determination of colossal magnetoresistance (CMR) associated with dc transport parallel to the film substrate and colossal magnetocapacitance (CMC) associated with ac transport in the perpendicular direction. We distinguish two distinct strain-related direction-dependent insulator-metal (IM) transitions and use Cole-Cole plots to establish a heretofore unobserved collapse of the dielectric response onto a universal scale-invariant power-law dependence over a large range of frequency, temperature and magnetic field.Comment: 32 pages, 4 figures, Supplementary section included, Submitted to Nature Physic

The membrane-associated form of cyclin D1 enhances cellular invasion

The essential G1-cyclin, CCND1, is a collaborative nuclear oncogene that is frequently overexpressed in cancer. D-type cyclins bind and activate CDK4 and CDK6 thereby contributing to G1–S cell-cycle progression. In addition to the nucleus, herein cyclin D1 was also located in the cytoplasmic membrane. In contrast with the nuclear-localized form of cyclin D1 (cyclin D1NL), the cytoplasmic membrane-localized form of cyclin D1 (cyclin D1MEM) induced transwell migration and the velocity of cellular migration. The cyclin D1MEM was sufficient to induce G1–S cell-cycle progression, cellular proliferation, and colony formation. The cyclin D1MEM was sufficient to induce phosphorylation of the serine threonine kinase Akt (Ser473) and augmented extranuclear localized 17β-estradiol dendrimer conjugate (EDC)-mediated phosphorylation of Akt (Ser473). These studies suggest distinct subcellular compartments of cell cycle proteins may convey distinct functions