Foreign body responses in central nervous system mimic natural wound responses and alter biomaterial functions

Biomaterials hold promise for diverse therapeutic applications in the central nervous system (CNS). Little is known about molecular factors that determine CNS foreign body responses (FBRs) in vivo , or about how such responses influence biomaterial function. Here, we probed these factors using a platform of injectable hydrogels readily modified to present interfaces with different representative physiochemical properties to host cells. We show that biomaterial FBRs mimic specialized multicellular CNS wound responses not present in peripheral tissues, which serve to isolate damaged neural tissue and restore barrier functions. Moreover, we found that the nature and intensity of CNS FBRs are determined by definable properties. For example, cationic, anionic or nonionic interfaces with CNS cells elicit quantifiably different levels of stromal cell infiltration, inflammation, neural damage and amyloid production. The nature and intensity of FBRs significantly influenced hydrogel resorption and molecular delivery functions. These results characterize specific molecular mechanisms that drive FBRs in the CNS and have important implications for developing effective biomaterials for CNS applications

Influence of dimensionality on superconductivity in carbon nanotubes

We investigate the electronic instabilities in carbon nanotubes (CNs), looking for the break-down of the one dimensional Luttinger liquid regime due to the strong screening of the long-range part of the Coulomb repulsion. We show that such a breakdown is realized both in ultra-small single wall CNs and multi wall CNs, while a purely electronic mechanism could explain the superconductivity (SC) observed recently in ultra-small (diameter $\sim 0.4 nm$) single wall CNs ($T_c\sim 15 ^{o}K$) and entirely end-bonded multi-walled ones ($T_c\sim 12 ^{o}K$). We show that both the doping and the screening of long-range part of the electron-electron repulsion, needed to allow the SC phase, are related to the intrinsically 3D nature of the environment where the CNs operate.Comment: 5 pages, 3 figures, PACS: 71.10.Pm,74.50.+r,71.20.Tx, to appear in J. Phys. Cond. Ma

Engaging Nursing Staff in Research: The Clinical Nurse Specialist Role in an Academic-Clinical Partnership

Purpose: The purpose of this article is to describe the processes of exploring and implementing an academic-clinical study, engaging nursing staff in research, and maintaining their enthusiasm within the context of an academic-clinical research partnership. Description: The core competencies of the clinical nurse specialist (CNS) role address evidence-based practice, quality improvement, and research. Studies and exemplars of the CNS role in the literature illustrate expert practitioner and facilitator of evidence-based practice, but less attention is given to methods used by the CNS to engage staff in clinical research. Outcome: The CNS was successful in obtaining staff engagement in the research project from exploration through sustainment. Conclusion: Collaborative research between academic and clinical partners enhances the educational and professional environment for students and clinicians, promotes evidence-based practice, and from this project may promote Veteran and family-centered care. The CNS played a key role in engaging and sustaining staff commitment, which contributed to the success of this study

The fate of Arabidopsis thaliana homeologous CNSs and their motifs in the Paleohexaploid Brassica rapa.

Following polyploidy, duplicate genes are often deleted, and if they are not, then duplicate regulatory regions are sometimes lost. By what mechanism is this loss and what is the chance that such a loss removes function? To explore these questions, we followed individual Arabidopsis thaliana-A. thaliana conserved noncoding sequences (CNSs) into the Brassica ancestor, through a paleohexaploidy and into Brassica rapa. Thus, a single Brassicaceae CNS has six potential orthologous positions in B. rapa; a single Arabidopsis CNS has three potential homeologous positions. We reasoned that a CNS, if present on a singlet Brassica gene, would be unlikely to lose function compared with a more redundant CNS, and this is the case. Redundant CNSs go nondetectable often. Using this logic, each mechanism of CNS loss was assigned a metric of functionality. By definition, proved deletions do not function as sequence. Our results indicated that CNSs that go nondetectable by base substitution or large insertion are almost certainly still functional (redundancy does not matter much to their detectability frequency), whereas those lost by inferred deletion or indels are approximately 75% likely to be nonfunctional. Overall, an average nondetectable, once-redundant CNS more than 30 bp in length has a 72% chance of being nonfunctional, and that makes sense because 97% of them sort to a molecular mechanism with deletion in its description, but base substitutions do cause loss. Similarly, proved-functional G-boxes go undetectable by deletion 82% of the time. Fractionation mutagenesis is a procedure that uses polyploidy as a mutagenic agent to genetically alter RNA expression profiles, and then to construct testable hypotheses as to the function of the lost regulatory site. We show fractionation mutagenesis to be a deletion machine in the Brassica lineage

Identification of the Content of Biologically Active Substances in Nut Shots

One of ways of the food industry development is a search for non-traditional raw material resources with the high content of physiologically healthy nutrients. A promising way of biologically important raw materials is secondary products of oil production, especially shots. The aim of the research was to determine the content of biologically active substances in nut shots (cedar nut shot (CNS) and walnut shot (WNS)). The quality composition of the phenol nature was established by reactions with 10 % alcohol solutions of FeCl3, NaOH, АlCl3 and cyanidin test. The content of hydroxycinnamic acids (with recalculation for chlorogenic acid) was determined by the spectrophotometric method. The amount of tanning substances – by the method of permanganometry. The analysis of the sum of flavonoids (in recalculation for rutin) was realized by the method of differential spectrophotometry. Carbonic acids were identified by the method of gas-liquid chromatography. There were revealed quality differences in the composition of substances of the phenol nature for CNS and WNS. WNS is characterized by the higher content of hydroxycinnamic acids – in 2,5 times, tanning substances – in 3,1 times and flavonoids – in 60 times, comparing with CNS. The content of unsaturated fats in WNS is 95,79 % of the total number of fats, and in CNS – 80,05 %. The ratio Omega-3/Omega-6 for the fat component of CNS is 1/0,06, and for WNS fats – 1/1,3. WNS comparing with CNS is characterized by the higher content of Malic (in 5,3 times) and fumaric (in 100 times)acid. CNS contains more lemon (in 2,9 times) and succinic (in 2,2 times) acid. That is, identification of the content of some biologically active substances in nut shots allows to recommend them for usage in technologies of food products. It allows to enrich them with phenol compounds, polyunsaturated fats and organic acids

Leucine Zipper-Bearing Kinase Is a Critical Regulator of Astrocyte Reactivity in the Adult Mammalian CNS.

Reactive astrocytes influence post-injury recovery, repair, and pathogenesis of the mammalian CNS. Much of the regulation of astrocyte reactivity, however, remains to be understood. Using genetic loss and gain-of-function analyses in vivo, we show that the conserved MAP3K13 (also known as leucine zipper-bearing kinase [LZK]) promotes astrocyte reactivity and glial scar formation after CNS injury. Inducible LZK gene deletion in astrocytes of adult mice reduced astrogliosis and impaired glial scar formation, resulting in increased lesion size after spinal cord injury. Conversely, LZK overexpression in astrocytes enhanced astrogliosis and reduced lesion size. Remarkably, in the absence of injury, LZK overexpression alone induced widespread astrogliosis in the CNS and upregulated astrogliosis activators pSTAT3 and SOX9. The identification of LZK as a critical cell-intrinsic regulator of astrocyte reactivity expands our understanding of the multicellular response to CNS injury and disease, with broad translational implications for neural repair

Mdivi-1, a mitochondrial fission inhibitor, modulates T helper cells and suppresses the development of experimental autoimmune encephalomyelitis.

BACKGROUND: Unrestrained activation of Th1 and Th17 cells is associated with the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). While inactivation of dynamin-related protein 1 (Drp1), a GTPase that regulates mitochondrial fission, can reduce EAE severity by protecting myelin from demyelination, its effect on immune responses in EAE has not yet been studied. METHODS: We investigated the effect of Mdivi-1, a small molecule inhibitor of Drp1, on EAE. Clinical scores, inflammation, demyelination and Drp1 activation in the central nervous system (CNS), and T cell responses in both CNS and periphery were determined. RESULTS: Mdivi-1 effectively suppressed EAE severity by reducing demyelination and cellular infiltration in the CNS. Mdivi-1 treatment decreased the phosphorylation of Drp1 (ser616) on CD4+ T cells, reduced the numbers of Th1 and Th17 cells, and increased Foxp3+ regulatory T cells in the CNS. Moreover, Mdivi-1 treatment effectively inhibited IFN-γ+, IL-17+, and GM-CSF+ CD4+ T cells, while it induced CD4+ Foxp3+ regulatory T cells in splenocytes by flow cytometry. CONCLUSIONS: Together, our results demonstrate that Mdivi-1 has therapeutic potential in EAE by modulating the balance between Th1/Th17 and regulatory T cells