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Remote limb conditioning (RLC), performed by intermittent interruption of blood flow to a limb, triggers endogenous tolerance mechanisms and improves stroke outcomes. The underlying mechanism for the protective effect involves a shift of circulating monocytes to a Ly6CHigh proinflammatory subset in normal metabolic conditions. The current study investigates the effect of RLC on stroke outcomes in subjects with obesity, a vascular comorbidity. Compared to lean mice, obese stroke mice displayed significantly higher circulating monocytes (monocytosis), increased CD45High monocytes/macrophages infiltration to the injured brain, worse acute outcomes, and delayed recovery. Unlike lean mice, obese mice with RLC at 2 hours post-stroke failed to shift circulating monocytes to pro-inflammatory status and nullified RLC-induced functional benefit. The absence of the monocyte shift was also observed in splenocytes incubated with RLC serum from obese mice, while the shift was observed in the cultures with RLC serum from lean mice. These results showed that the alteration of monocytosis and subsets underlies negating RLC benefits in obese mice and suggest careful considerations of comorbidities at the time of RLC application for stroke therapy. [ABSTRACT FROM AUTHOR]

CD36 expressed in multiple cell types regulates inflammation, vascular function, and innate immunity. Specifically, CD36 in microvascular endothelial cells (ECs) signals to elicit inflammation and causes EC death. This study investigated roles for EC-CD36 on acute stroke pathology in normal and obese conditions. Obesity induced by a high-fat diet (HD) selectively increased CD36 expression in ECs, not in monocytes/macrophages, in the post-ischemic brain. Mice deficient CD36 in ECs (ECCD36−/−) showed reduced injury size and vascular permeability in normal conditions. While control mice fed a HD developed obesity and aggravated stroke injury, ECCD36−/− mice were resistant to develop an obesity phenotype. Subjecting ECCD36−/− mice to stroke resulted in reduced injury size and BBB disruption. Moreover, the mice had reduced MCP-1 and CCR2 gene expression, resulting in reduced monocyte trafficking with improved survival and acute motor function. Reduced MCP-1 and CCR2 expression was still evident in ECCD36−/− mice subjected to severe stroke, suggesting that monocyte trafficking is an infarct-independent metabolic effect associated with specific EC-CD36 deletion. Our findings demonstrate the importance of EC-CD36 in developing vascular comorbidities and suggest that targeting EC-CD36 is a potential preventative strategy to normalize vascular risk factors, leading to improved acute stroke outcomes. [ABSTRACT FROM AUTHOR]

Background: Monocyte-derived macrophages (MDMs) and microglia elicit neural inflammation and clear debris for subsequent tissue repair and remodeling. The role of infiltrating MDMs in the injured brain, however, has been controversial due to overlapping antigen expression with microglia. In this study, we define the origin and function of MDMs in cerebral ischemia.Methods: Using adoptive transfer of GFP+ splenocytes into adult asplenic mice subjected to transient middle cerebral artery occlusion, we compared the role of CD11b+/CD45+/NK1.1-/Ly6G- MDMs and microglia in the ischemic brain. The phagocytic activities of MDMs and microglia were measured by the uptake of fluorescent beads both in vivo with mice infused with GFP+ splenocytes and ex vivo with cultures of isolated brain immune cells.Results: Stroke induced an infiltration of MDMs [GFP+] into the ipsilateral hemisphere at acute (3 days) and sub-acute phases (7 days) of post-stroke. At 7 days, the infiltrating MDMs contained both CD45High and CD45Low subsets. The CD45High MDMs in the injured hemisphere exhibited a significantly higher proliferation capacity (Ki-67 expression levels) as well as higher expression levels of CD11c when compared to CD45Low MDMs. The CD45High and CD45Low MDM subsets in the injured hemisphere were approximately equal populations, indicating that CD45High MDMs infiltrating the ischemic brain changes their phenotype to CD45Low microglia-like phenotype. Studies with fluorescent beads reveal high levels of MDM phagocytic activity in the post-stroke brain, but this phagocytic activity was exclusive to post-ischemic brain tissue and was not detected in circulating monocytes. By contrast, CD45Low microglia-like cells had low levels of phagocytic activity when compared to CD45High cells. Both in vivo and ex vivo studies also show that the phagocytic activity in CD45High MDMs is associated with an increase in the CD45Low/CD45High ratio, indicating that phagocytosis promotes MDM phenotype conversion.Conclusions: This study demonstrates that MDMs are the predominant phagocytes in the post-ischemic brain, with the CD45High subset having the highest phagocytic activity levels. Upon phagocytosis, CD45High MDMs in the post-ischemic brain adopt a CD45Low phenotype that is microglia-like. Together, these studies reveal key roles for MDMs and their phagocytic function in tissue repair and remodeling following cerebral ischemia. [ABSTRACT FROM AUTHOR]

When a laminated composite structure with curvature is subjected to a bending load, the most important failure mode is due to delamination in curved regions. In this study, the reinforcement effect of grooved Z-pins is investigated for preventing delamination of curved beams. Through a four-point bending test, the effect of stainless-steel pin diameter and areal density on bending failure of curved beams is studied. For areal pin densities of 0.5, 1.0, and 2.0%, pin diameters of 0.3 and 0.5 mm result in average pin strength increases of 21, 27, and 42% and 8.7, 12, and 32%, respectively. When the pin size is small, the pin is inserted closer to 90° from the mid-plane, a smaller resin-rich zone is generated, and there is less laminate damage. [ABSTRACT FROM AUTHOR]

This study analyzed the effects of hygrothermal conditions on the single-lap shear strength of a carbon fiber/poly-ether-ketone-ketone (CF/PEKK) thermoplastic composite material fabricated by induction welding. Specimens were exposed to an 85 °C/85% environment using a temperature and humidity chamber to identify the effect of moisture on single-lap shear strength, while their moisture saturation was assessed through weight measurement. Single-lap shear strength tests were performed on the dried and saturated specimens at 25 °C and 100 °C to 180 °C at 20 °C intervals. At 160 °C, the strength of the CF/PEKK thermoplastic composites rapidly declined to 76% (dried specimens) and 78% (moist specimens). The fracture surfaces and failure modes were analyzed using scanning electron microscopy images, which confirmed an increase in the degraded areas and naked fibers at higher testing temperatures. In addition, it was found that exposure to a moist environment changes the failure mode from fiber bundles and fiber/matrix failure to naked fiber and matrix failure owing to the reduction in interfacial adhesion properties. The findings confirmed that hygrothermal conditions directly affect the degradation of the CF/PEKK thermoplastic composites and that a rapid reduction in the single-lap shear strength occurs above Tg. [ABSTRACT FROM AUTHOR]

Despite significant medical benefits as in space exploration or emergency care, prolonged torpidity of non-hibernator mammals remains unexplored to date. Here, we report that male Institute of Cancer Research mice could sustain two separate 2-day torpor bouts and maintain body temperature of 28-33°C following repeated treatments of 3-iodothyronamine (TAM), a natural derivative of thyroid hormone. A 1-day interbout arousal period, adopted to mimic the behavior of true hibernators, seemed critical for the subjects to restore physiological homeostasis. Molecular studies of neuron-specific enolase, S100 calcium binding protein B and heat shock protein 72 suggested that the brain maintains functional and cytoprotective activities during sustained torpidity. Together, the results of this study propose a practical protocol using a torpor-arousal cycle that can be applied to the extreme medical situations. J. Cell. Physiol. 226: 853-858, 2011. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

This paper presents details of the mechanical properties related to the static and fatigue strength of carbon fiber reinforced polyetherketoneketone (CF/PEKK) thermoplastic induction-welded composite joints. To better understand the process parameters, the finite element modeling (FEM) of the heat distribution was analyzed based on the generator power, coil coupling distance, coil moving speed, frequency, compaction force, and coil geometry while maintaining the optimal coil speed. The temperature behavior calculated using the simulation model exhibited good agreement with experimental results. A microscopic inspection, non-destructive test (NDT) was conducted to check the morphology characteristics of the welded joints. To check the mechanical performance of the induction-welded specimens, single-lap shear strength (SLSS) tests under static and cyclical fatigue loading conditions were conducted to check the weld qualities from a practical perspective. The mechanical testing results indicated that the static and cyclical fatigue specimens were dominated by a cohesive failure mode with a light fiber tear (LFT). These results suggested that using the optimal process parameters based on multi-physics FEM simulation could potentially improve mechanical performance. [ABSTRACT FROM AUTHOR]

Conessine, a steroidal alkaloid isolated from Holarrhena floribunda, has anti-malarial activity and interacts with the histamine H3 receptor. However, the cellular effects of conessine are poorly understood. Accordingly, we evaluated the involvement of conessine in the regulation of autophagy. We searched natural compounds that modulate autophagy, and conessine was identified as an inhibitor of autophagic flux. Conessine treatment induced the formation of autophagosomes, and p62, an autophagic adapter, accumulated in the autophagosomes. Reactive oxygen species such as hydrogen peroxide (H2O2) result in muscle cell death by inducing excessive autophagic flux. Treatment with conessine inhibited H2O2-induced autophagic flux in C2C12 myoblast cells and also interfered with cell death. Our results indicate that conessine has the potential effect to inhibit muscle cell death by interfering with autophagic flux. [ABSTRACT FROM AUTHOR]