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Recent advances in polymer science make it possible to create single chain polymer nanoparticles (SCNPs), which can mimic the folding of natural macromolecules, such as protein and nucleic acid, in terms of their native and functional state. Even though considerable progress has been done during the last years, the synthesis of relatively controlled SCNPs with a good folding accuracy is still challenging due to lack of appropriate chemical synthesis techniques. Different types of SCNPs are developed with enhanced properties and used for various applications, e.g., delivery systems, imaging agents, and nanomedicine. As it is believed that SCNPs are so crucial to elucidate single chain technology, in this review, recent developments in SCNPs are discussed comprehensively according to their synthetic approaches to keep readers updated on this important research field. First, selective point folding methods are classified and highlighted, and then repeat unit folding routes are discussed with exciting examples. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's Disease (AD), the most common form of dementia among the elderly, is characterized by the progressive decline of cognitive function. Although production and accumulation of amyloid beta (Aβ), particularly soluble Aβ oligomers, is central to the pathogenesis of AD, monoclonal antibodies targeted against the Aβ oligomers have failed to modify the disease progression clinically despite confirmed target engagement. Here we present, characterization of 3xTg‐AD mouse model treated with an engineered recombinant tandem protein consisting of a WASH complex member FAM21 linked with Retromer complex member VSP35 in order to stabilize these intrinsically disordered proteins. In addition, we present complete rescue of autophagic flux deficiencies and lipid accumulation phenotypes seen in iPSCs (from non‐familial AD patients)‐derived neurons and microglia with this therapeutic tandem protein. We will discuss our findings as a novel disease modifying treatment for Alzheimer's Disease. Method: By using proteomics, biochemical analysis and iPSCs‐derived neurons and microglia, we have characterized a recombinantly produced fusion protein's (FAM21/VPS35) utility in reduction of the accumulation of soluble amyloid β oligomers; resolution of autophagic flux deficiencies and misfolded protein burden and neural degeneration in vitro and 3xTg‐AD in vivo model of AD. Result: Treatment of 3xTg‐AD mice and iPSCs‐derived neurons and glial cells with a novel recombinant therapeutic protein resulted in a statistically significant reduction of accumulation of soluble amyloid Aβ oligomers and neural degeneration; reversal of autophagic flux and lipid deregulation. Conclusion: Therapeutic modulation of WASH Complex‐Retromer interactions merits further analysis especially in early AD & mild cognitive impairment for its potential neuroprotective and disease modifying effects. [ABSTRACT FROM AUTHOR]

This paper examines the relationship between business group affiliation and stock price informativeness in an emerging market setting. We use stock price synchronicity as a measure, and study the impact of group affiliation ‐specifically the extent of affiliation, ownership structure and existence of group bank‐ on firm specific information content. Results reveal that the amount of firm‐specific information capitalized into stock prices tends to be lower (higher) when the firm is group‐affiliated (unaffiliated), indirectly (directly) owned, and affiliated group has (does not have) a group bank. Additionally, the extent of group affiliation maintains a non‐linear relationship with synchronicity, suggesting that the perception of higher versus lower levels of group ownership differs. [ABSTRACT FROM AUTHOR]

Targeting in a cellular level is still one of the major challenges in biomedical treatments. However, new synthetic and analytical techniques now allow the development of precisely prepared macromolecules. Thus, glycopolymer chains are reported to be prepared with controlled length, monomer sequences, as well as chain‐folded structures. A high level of complexity in synthetic macromolecules also allows increased selectivity in targeting, which is a key factor in biomedical applications. [ABSTRACT FROM AUTHOR]

Glycopolymers are synthetic-carbohydrate-containing materials capable of interacting and binding to specific targeting lectins, which are crucially important in many biologically active processes. Over the last decade, advances in synthetic chemistry and polymerization techniques have enabled the development of sequence and architecturally controlled glycopolymers for different types of bioapplications, such as drug delivery and release purposes, gene therapy, lectin-based biosensors, and much more in the future. These precision glycopolymers are able to mimic structural and functional features of the naturally existing glycocalyx. Furthermore, self-assembled glycopolymers could enhance specific and selective recognition properties on multivalent scaffolds in glycoscience. This mini-review will focus on production methods and recent advances in precision synthesis and self-assembly of glycopolymers. Additionally, possible contributions of single-chain folding in glycopolymers will be discussed as a future prospect. [ABSTRACT FROM AUTHOR]

Inflammation and microvascular dysfunction have been implicated in a variety of pathologic conditions affecting the brain. Features of the inflammatory response that are common to many of these pathological conditions and that are manifested in the neurovasculature include oxidative stress, diminished endothelial barrier function (increased vascular permeability), increased expression of endothelial cell adhesion molecules, and the recruitment of rolling and adherent leukocytes and platelets. The evidence implicating leukocyte-endothelial cell adhesion in cerebral microvessels as a rate-determining component of the pathophysiology associated with conditions such as ischemia-reperfusion, sickle cell disease, and γ -irradiation is summarized. Mechanisms that have been proposed to explain the recruitment of adherent leukocytes and platelets in the diseased/injured cerebral microvasculature are also addressed, and a common paradigm for blood cell recruitment induced by seemingly unrelated pathological conditions is outlined. Although there are many structural and functional characteristics of the cerebral microvasculature that distinguish it from other regional vascular beds, the processes that underlie the recruitment of injury-causing inflammatory cells in the brain appear to closely resemble those described for other tissues. [ABSTRACT FROM AUTHOR]

The synthesis of brush glycopolymers mimicking the architecture of proteoglycans is achieved by grafting sequence‐defined glycooligomers derived from solid‐phase polymer synthesis onto a poly(active ester) scaffold. This approach gives access to a first library of brush glycopolymers with controlled variations in the degree of branching and number of carbohydrate ligands per branch. When studying lectin binding of linear and brush glycopolymers to lectins Concanavalin A (ConA), dendritic cell‐specific intercellular adhesion molecule‐3‐grabbing non‐integrin (DC‐SIGN), and mannose‐binding lectin (MBL), different preferences are observed with MBL showing higher binding to linear glycopolymer and ConA and DC‐SIGN favoring brush glycopolymers. This finding suggests that the architecture of polymeric glycan mimetics affects binding to lectins not only in terms of creating higher avidity but potentially also selectivity ligands. [ABSTRACT FROM AUTHOR]

The therapeutic potential of bone marrow stromal cells (BMSC) has been demonstrated in stroke. However there is limited information about the potential neuroprotective factors that BMSC secrete in the infarcted brain. The objective of this study was to isolate BMSC from infarcted regions of the postischemic brain and to compare the expression of genes for extracellular factors produced by transplanted BMSC that have infiltrated brain tissue to their naïve counterparts. Ischemic stroke was induced in C57BL/6 mice by middle cerebral artery occlusion for 1 h, followed by 24 h reperfusion. BMSC were isolated from H-2Kb-tsA58 mice (cells can grow at 33°C). BMSC were administered i.v. at 24 h of reperfusion. Mice were sacrificed 1 week after administration of BMSC. Infarcted hemispheres were removed and cultured at 33°C for BMSC isolation. Affymetrix microarray analysis was performed to compare the gene expression patterns between the BMSC populations in 6 mice. Pair-wise analysis detected 93 extracellular factor genes that were upregulated (≥2 fold) between naïve and infiltrated BMSC. Fibroblast growth factors, bone morphogenetic proteins, neurotrophic factors, and catalase were among the most highly expressed genes detected. Extracellular factors secreted by protective BMSC following infiltration into postischemic brain may represent novel therapeutic approach for treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

The therapeutic potential of bone marrow stromal cells (BMSC) has been demonstrated in different models of stroke. While it is well known that BMSC migrate and home to the site of brain injury, the mechanism underlying this cell recruitment is not known. We hypothesize that after stroke, cerebrovascular endothelium expresses adhesion molecules that allow BMSC to recognize and home to the injury site. Stroke was induced in C57BL/6 mice by middle cerebral artery occlusion (MCAo) for 1 h, followed by 24 h reperfusion (MCAo/R). BMSC from H-2Kb-tsA58 mice were fluorescently labeled and administered (24 h after stroke) i.v. with or without an E- or P-selectin blocking antibody. BMSC were observed in cortical vessels using intravital microscopy. Significant adhesion (76±5 cells/mm²) of BMSC was observed in venules after MCAo/R, while a low number of adherent BMSC was detected in sham mice (16±4 cells/mm²). E- and P-selectin antibodies blocked the adhesion of BMSC in cerebral venules after stroke (36 ±4 & 10±3 cells/mm² respectively). These findings indicate that cerebral endothelium assume a pro-adhesive phenotype following MCAO/R that favors the recruitment of BMSC into the infarct area. This adhesive interface between the blood and endothelial cell surface represents an important therapeutic target for enhancement of stem cell delivery to sites of ischemic infarction following stroke. [ABSTRACT FROM AUTHOR]

Obesity is a well-documented and modifiable risk factor for ischemic stroke. We tested the hypothesis that obesity exacerbates the microvascular dysfunction and brain damage induced by ischemia-reperfusion (I/R). Middle cerebral artery occlusion (30 min) and reperfusion was induced in wild type (WT) and leptin-deficient ob/ob mice. The adhesion of leukocytes (LA) and platelets (PA) in postischemic cerebral venules was monitored after 4 hrs of reperfusion by intravital microscopy. Infarct volume was estimated from brain slices (obtained 24 hrs after reperfusion) using the TTC staining method. Blood-brain barrier dysfunction was quantified using the Evans blue (EB) method. Brain water (WC) content was determined as (wet weight-dry weight)/wet weight (%). I/R elicited significant increases in LA (116 ± 82 vs 308 ± 202 cells/mm²) and PA in cerebral venules of both WT and ob/ob mice, however the responses were exaggerated in ob/ob mice. A similar pattern of I/R-induced increases in infarct volume (16.4 ± 6.0 vs 27.6 ± 3.2 %), EB extravasation (0.013 ± 0.0082 vs 0.031 ± 0.012), and WC (79.8 ± 0.62 vs 81.3 ± 0.31%) was noted in WT and ob/ob mice, with the latter group exhibiting more profound changes. These findings indicate that the microvascular dysfunction and brain injury after I/R is exaggerated in ob/ob mice and that obesity leads to greater morbidity following ischemic stroke. [ABSTRACT FROM AUTHOR]