Design considerations for protective boots for first responders to hazardous materials incidents.

First responder professionals are at high risk for work-related injuries (e.g., extreme temperatures, chemical and biological threats); boots are essential to ensure body protection since they have full contact with the ground in all scenarios. A substantial body of work has investigated the necessity of improvements in protective boots, but there is limited research conducted on boots with fit-adjustable fasteners for secure and adjustable fit within this context. Thus, this study explored the areas for improvement in boot design for the development of form-fitting and yet comfortable boots focusing on two different boot designs, prototype all-hazards tactical boots (lace-up) and rubber boots (slip-on). Findings indicated that the boot design should address participants' concerns with the material choices of boots, specifically with bulkiness, weight, and flexibility. Our findings provide insights into boot material and design choices to improve protective boots for first responders.

ZNF598 co-translationally titrates poly(GR) protein implicated in the pathogenesis of C9ORF72-associated ALS/FTD.

C9ORF72-derived dipeptide repeat proteins have emerged as the pathogenic cause of neurodegeneration in amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). However, the mechanisms underlying their expression are not fully understood. Here, we demonstrate that ZNF598, the rate-limiting factor for ribosome-associated quality control (RQC), co-translationally titrates the expression of C9ORF72-derived poly(GR) protein. A Drosophila genetic screen identified key RQC factors as potent modifiers of poly(GR)-induced neurodegeneration. ZNF598 overexpression in human neuroblastoma cells inhibited the nuclear accumulation of poly(GR) protein and decreased its cytotoxicity, whereas ZNF598 deletion had opposing effects. Poly(GR)-encoding sequences in the reporter RNAs caused translational stalling and generated ribosome-associated translation products, sharing molecular signatures with canonical RQC substrates. Furthermore, ZNF598 and listerin 1, the RQC E3 ubiquitin-protein ligase, promoted poly(GR) degradation via the ubiquitin-proteasome pathway. An ALS-relevant ZNF598R69C mutant displayed loss-of-function effects on poly(GR) expression, as well as on general RQC. Moreover, RQC function was impaired in C9-ALS patient-derived neurons, whereas lentiviral overexpression of ZNF598 lowered their poly(GR) expression and suppressed proapoptotic caspase-3 activation. Taken together, we propose that an adaptive nature of the RQC-relevant ZNF598 activity allows the co-translational surveillance to cope with the atypical expression of pathogenic poly(GR) protein, thereby acquiring a neuroprotective function in C9-ALS/FTD.

Synthesis and NOx removal performance of anatase S-TiO2/g-CN heterojunction formed from dye wastewater sludge.

In this study, sludges generated from Ti-based flocculation of dye wastewater were used to retrieve photoactive titania (S-TiO2). It was heterojunctioned with graphitic carbon nitride (g-CN) to augment photoactivity under UV/visible light irradiance. Later the as-prepared samples were utilized to remove nitrogen oxides (NOx) in the atmospheric condition through photocatalysis. Heterojunction between S-TiO2 and g-CN was prepared through facile calcination (@550 °C) of S-TiO2 and melamine mix. Advanced sample characterization was carried out and documented extensively. Successful heterojunction was confirmed from the assessment of morphological and optical attributes of the samples. Finally, the prepared samples' level of photoactivity was assessed through photooxidation of NOx under both UV and visible light irradiance. Enhanced photoactivity was observed in the prepared samples irrespective of the light types. After 1 h of UV/visible light-based photooxidation, the best sample STC4 was found to remove 15.18% and 9.16% of atmospheric NO, respectively. In STC4, the mixing ratio of S-TiO2, to melamine was maintained as 1:3. Moreover, the optical bandgap of STC4 was found as 2.65 eV, where for S-TiO2, it was 2.83 eV. Hence, the restrained rate of photogenerated charge recombination and tailored energy bandgap of the as-prepared samples were the primary factors for enhancing photoactivity.

Toxic effects of dietary copper and EGCG on bioaccumulation, antioxidant enzyme and immune response of Korean bullhead, Pseudobagrus fulvidraco.

There are few reports of dietary Cu (copper) toxicity to Korean bullhead, Pseudobagrus fulvidraco, and little is known about recovery from dietary Cu exposure. In this study, P. fulvidraco (mean length 16.9 ± 1.38 cm, and mean weight 53.2 ± 1.22 g) were exposed for 4 weeks to dietary Cu concentration of 0 (control), 700, 900, and 1100 mg Cu kg-1 dry feed to establish maximum tolerable levels of dietary Cu. All fish were then fed the dietary EGCG (Epigallocatechin gallate) concentration of 100 and 500 mg EGCG kg-1 dry feed for a further 2 weeks to assess recovery. We were measured bioaccumulation (in the intestine, liver, and gill tissue), antioxidant enzymes (SOD and CAT) and immune responses (lysozyme and phagocytosis). The Cu exposure induced a significant accumulation in the intestine, liver, and gill tissues and the highest accumulation was observed in intestinal tissues (17-34 fold), but dietary EGCG exposure decreased (about 0.8-fold) Cu concentration in each tissue (ANOVA, P < 0.05). In antioxidant enzymes, SOD and CAT significantly increased by approximately 1.6-fold by dietary Cu exposure in the liver and gill tissue, respectively, but dietary EGCG exposure decreased SOD and CAT by about 1.1-fold, respectively (ANOVA, P < 0.05). For immune responses, lysozyme and phagocytosis in the blood significantly were decreased by approximately 1.5-fold, respectively, by dietary Cu exposure, but dietary EGCG exposure increased lysozyme and phagocytosis by about 1.1-fold, respectively (ANOVA, P < 0.05). During recovery period, bioaccumulation, antioxidant enzymes (SOD and CAT activity), and immune response (lysozyme and phagocytosis activity) tended to alleviate the significant changes by Cu exposure, and the tendency to return normal state was observed in high level of EGCG. The result of this study indicate that Cu exposure to P. fulvidraco affects bioaccumulation, antioxidant enzymes, and immune responses, and high level of EGCG were effective to alleviate the toxic effects of Cu exposure.

Facile synthesis and characterization of anatase TiO2/g-CN composites for enhanced photoactivity under UV-visible spectrum.

For the purpose of atmospheric NO removal, anatase TiO2/g-CN photocatalytic composites were prepared by using a facile template-free calcination route in atmospheric conditions. Considerably fiscal NP400 and laboratory-grade melamine were used as the precursor of the composites. Additionally, samples were prepared with different wt. ratios of TiO2 and melamine by using two distinct calcination temperatures (550 °C/600 °C). The morphological attributes of the composites were assessed with X-ray diffraction, scanning and transmission electron microscopy, infrared spectroscopy, and X-ray photoelectron spectroscopy. Additionally, the optical traits were evaluated and compared using UV-visible diffuse reflectance spectroscopy and photoluminescence analysis. Finally, the photodegradation potentials for atmospheric NO by using the as-prepared composites were assessed under both UV and visible light irradiation. All the composites showed superior NO oxidation compared to NP400 and bulk g-CN. For the composites prepared by using the calcination temperature of 550 °C, the maximum NO removal was observed when the NP400 to melamine ratio was 1:2, irrespective of the utilized light irradiation type. Whereas for increased calcination temperature (600 °C), the maximum NO removal was observed at the precursor mix ratio of 1:3 (NP400:melamine). Successfully narrowed energy bandgaps were perceived in the as-prepared composites. Moreover, a subsequent drop in NO2 generation during NO oxidation was observed under both UV and visible light irradiation. Interestingly, higher calcination temperature during the synthesis of the catalysts has shown a significant drop in NO2 generation during the photodegradation of NO.

Changes in Hematological Parameters and Heat Shock Proteins in Juvenile Sablefish Depending on Water Temperature Stress.

Juvenile Sablefish Anoplopoma fimbria were used to assess the effects of water temperature (8, 10, 12, 14, 16, 18, and 20°C) on hematological parameters and heat shock proteins 70 and 90 for 4 months. Hematological parameters, including red blood cell count, hematocrit, and hemoglobin, were significantly decreased at 18°C. The inorganic plasma components calcium and magnesium were not altered by water temperature. The organic plasma components glucose and cholesterol were notably elevated at 18°C, whereas total protein was reduced. The enzymatic components, including aspartate aminotransferase, alanine aminotransaminase, and alkaline phosphatase, were notably elevated at 16°C or 18°C. The results of this study indicate that a temperature higher than the proper temperature affects the hematological parameters and heat shock proteins of juvenile Sablefish.

Toxic Effects and Depuration on the Antioxidant and Neurotransmitter Responses after Dietary Lead Exposure in Starry Flounder.

Starry Flounder Platichthys stellatus were exposed to dietary lead (Pb) at concentrations of 0, 30, 60, 120, and 240 mg/kg for 4 weeks. Recover period was conducted for 2 weeks after the exposure. Exposure to Pb concentrations over 60 mg/kg induced significant changes in the antioxidant responses in the liver, kidney, and gill and continued even after the depuration period in the liver (over 120 mg/kg for superoxide dismutase [SOD] activity) and kidney (at 240 mg/kg for glutathione [GSH] levels). Glutathione S-transferase (GST) activity in liver, kidney, and gill were increased by dietary Pb exposure, and recovery was observed in all groups during the recovery period. Acetylcholinesterase (AChE) activity was significantly inhibited in the brain and muscle of flounder at Pb exposure over 120 mg/kg, and no restoration was observed after the depuration period. Lysozyme activity in the plasma was significantly increased at Pb exposures greater than 60 mg kg but was restored after the depuration period. The results of this study indicate that dietary Pb exposure induces toxic effects on antioxidant responses, neurotransmitter, and immune responses of Starry Flounder.

Alterations in growth performance and stress responses in juvenile rockfish, Sebastes schlegelii, exposed to dietary chromium with varying levels of dietary ascorbic acid supplementation.

Juvenile rockfish Sebastes schlegelii (mean length 10.8 ± 1.4 cm, and mean weight 31.7 ± 3.6 g) were exposed for 4 weeks to different levels of dietary chromium (Cr6+) at 0, 120, and 240 mg/L and ascorbic acid (AsA) at 100, 200, and 400 mg/L. Growth performance of S. schlegelii was significantly decreased due to dietary Cr exposure, whereas lysozyme activity was notably increased. Exposure to dietary Cr resulted in substantial accumulation of Cr in the blood. Levels of two stress indicators, plasma cortisol and heat shock protein 70, of S. schlegelii were increased due to dietary Cr exposure. The results indicated that dietary Cr exposure affected growth performance, lysozyme activity, and stress responses of S. schlegelii, and high levels of AsA supplementation significantly attenuated dietary Cr-induced toxicity.

Toxic effects of juvenile sablefish, Anoplopoma fimbria by ammonia exposure at different water temperature.

Juvenile sablefish, Anoplopoma fimbria (mean length 17.1±2.4cm, and mean weight 75.6±5.7g) were used to evaluate toxic effects on antioxidant systems, immune responses, and stress indicators by ammonia exposure (0, 0.25, 0.75, and 1.25mg/L) at different water temperature (12 and 17°C) in 1 and 2 months. In antioxidant responses, superoxide dismutase (SOD) and catalase (CAT) were significantly increased by ammonia exposure, whereas glutathione (GSH) was decreased. In immune responses, lysozyme and phagocytosis activity were significantly increased by ammonia exposure. In stress indicators, plasma glucose, heat shock protein 70 (HSP 70), and cortisol were significantly increased. At high water temperature (17°C), alterations by ammonia exposure were more distinctly. The results of this study indicated that ammonia exposure can induce toxic effects in the sablefish, and high water temperature can affect the ammonia exposure toxicity.

Growth performance, oxidative stress, and non-specific immune responses in juvenile sablefish, Anoplopoma fimbria, by changes of water temperature and salinity.

Juvenile sablefish, Anoplopoma fimbria (mean length 15.5 ± 1.9 cm, mean weight 68.5 ± 4.8 g), were used to evaluate the effects on growth, oxidative stress, and non-specific immune responses by changes of water temperature (8, 10, 12, 14, 16, 18, and 20 °C) and salinity (100 (35.0), 90 (31.5), 80 (28.0), 70 (24.5), 60 (21.0), 50 (17.5), and 40% (14.0) (‰)) for 4 months. The growth performance was significantly increased at the temperature of 12 and 14 °C, and the feed efficiency was notably decreased at the temperature of 18 °C. The growth performance and feed efficiency were also significantly decreased at low salinity. The antioxidant responses such as superoxide dismutase and catalase were significantly increased by the high temperature and decreased by the low salinity. The immune responses such as lysozyme and phagocytosis were elevated by the temperature of 18 °C and decreased by the salinity of 50%. The results of this study indicate that the growth performance of juvenile sablefish, A. fimbria, is influenced by the temperature and salinity, and the excessive temperature and salinity levels can affect the antioxidant and immune responses.

D-AKAP1a is a signal-anchored protein in the mitochondrial outer membrane.

Dual A-kinase anchoring protein 1a (D-AKAP1a, AKAP1) regulates cAMP signaling in mitochondria. However, it is not clear how D-AKAP1a is associated with mitochondria. In this study, we show that D-AKAP1a is a transmembrane protein in the mitochondrial outer membrane (MOM). We revealed that the N-terminus of D-AKAP1a is exposed to the intermembrane space of mitochondria and that its C-terminus is located on the cytoplasmic side of the MOM. Moderate hydrophobicity and the positively charged flanking residues of the transmembrane domain of D-AKAP1a were important for targeting. Taken together, D-AKAP1a can be classified as a signal-anchored protein in the MOM. Our topological study provides valuable information about the molecular and cellular mechanisms of mitochondrial targeting of AKAP1.

Glycoepitopes of staphylococcal wall teichoic acid govern complement-mediated opsonophagocytosis via human serum antibody and mannose-binding lectin.

Serum antibodies and mannose-binding lectin (MBL) are important host defense factors for host adaptive and innate immunity, respectively. Antibodies and MBL also initiate the classical and lectin complement pathways, respectively, leading to opsonophagocytosis. We have shown previously that Staphylococcus aureus wall teichoic acid (WTA), a cell wall glycopolymer consisting of ribitol phosphate substituted with α- or ß-O-N-acetyl-d-glucosamine (GlcNAc) and d-alanine, is recognized by MBL and serum anti-WTA IgG. However, the exact antigenic determinants to which anti-WTA antibodies or MBL bind have not been determined. To answer this question, several S. aureus mutants, such as α-GlcNAc glycosyltransferase-deficient S. aureus ΔtarM, ß-GlcNAc glycosyltransferase-deficient ΔtarS, and ΔtarMS double mutant cells, were prepared from a laboratory and a community-associated methicillin-resistant S. aureus strain. Here, we describe the unexpected finding that ß-GlcNAc WTA-deficient ΔtarS mutant cells (which have intact α-GlcNAc) escape from anti-WTA antibody-mediated opsonophagocytosis, whereas α-GlcNAc WTA-deficient ΔtarM mutant cells (which have intact ß-GlcNAc) are efficiently engulfed by human leukocytes via anti-WTA IgG. Likewise, MBL binding in S. aureus cells was lost in the ΔtarMS double mutant but not in either single mutant. When we determined the serum concentrations of the anti-α- or anti-ß-GlcNAc-specific WTA IgGs, anti-ß-GlcNAc WTA-IgG was dominant in pooled human IgG fractions and in the intact sera of healthy adults and infants. These data demonstrate the importance of the WTA sugar conformation for human innate and adaptive immunity against S. aureus infection.

RG-II from Panax ginseng C.A. Meyer suppresses asthmatic reaction.

In asthma, T helper 2 (T(H)2)-type cytokines such as interleukin (IL)-4, IL-5, and IL-13 are produced by activated CD4(+) T cells. Dendritic cells played an important role in determining the fate of naive T cells into either T(H)1 or T(H)2 cells. We determined whether RG-II regulates the T(H)1/T(H)2 immune response by using an ovalbumin-induced murine model of asthma. RG-II reduced IL-4 production but increased interferon- gamma production, and inhibited GATA-3 gene expression. RG-II also inhibited asthmatic reactions including an increase in the number of eosinophils in bronchoalveolar lavage fluid, an increase in inflammatory cell infiltration in lung tissues, airway luminal narrowing, and airway hyperresponsiveness. This study provides evidence that RG-II plays a critical role in ameliorating the pathogenic process of asthmatic inflammation in mice. These findings provide new insights into the immunotherapeutic role of RG-II in terms of its effects in a murine model of asthma.

Comparative study of the effects of different growth hormone doses on growth and spatial performance of hypophysectomized rats.

This study was designed to examine the effects of recombinant human growth hormone replacement on somatic growth and cognitive function in hypophysectomized (HYPOX) female Sprague-Dawley rats. Rats (5 per group) were randomized by weight to 3 experimental groups: group 1, administered 200 microg/kg of GH once daily for 9 days; group 2, administered 200 microg/kg of GH twice daily; and group 3, administered saline daily. Somatic growth was evaluated by measurement of body weight daily and of the width of the proximal tibial growth plate of the HYPOX rats. Cognitive function was evaluated using the Morris water maze (MWM) test. The results indicated that GH replacement therapy in HYPOX rats promoted an increase in the body weight and the width of the tibial growth plate in a dose-dependent manner. On the third day of the MWM test, the escape latency in the GH-treated groups 1 and 2 was significantly shorter than that in the control rats (P<0.001 and P=0.032, respectively), suggesting that rhGH improved spatial memory acquisition in the MWM test. Therefore it is concluded that rhGH replacement therapy in HYPOX rats stimulates an increase in somatic growth in a dose-dependent manner and also has beneficial effects on cognitive functions.

Apigenin protects ovalbumin-induced asthma through the regulation of GATA-3 gene.

Apigenin, a dietary plant-flavonoid has shown anti-inflammatory and anticancer properties, however the molecular basis of this effect remains to be elucidated. Thus we elucidated to anti-allergic effect of apigenin in ovalbumin (OVA)-induced asthma model mice. The OVA-induced mice showed allergic airway reactions. It included an increase in the number of eosinophils in bronchoalveolar lavage (BAL) fluid, an increase in inflammatory cell infiltration into the lung around blood vessels and airways, airway luminal narrowing, and the development of airway hyper-responsiveness (AHR). The administration of apigenin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, this study may provide evidence that apigenin plays a critical role in the amelioration of the pathogenetic process of asthma in mice. These findings provide new insight into the immunopharmacological role of apigenin in terms of its effects in a murine model of asthma.

TLR-4 agonistic lipopolysaccharide upregulates interleukin-8 at the transcriptional and post-translational level in vascular smooth muscle cells.

Despite extensive studies on cellular responses to activation of Toll-like receptor-4 (TLR-4), it is not evident weather its activation affects gene expression of interleukin-8 (IL-8) in vascular smooth muscle cells (VSMCs). Therefore, this study has investigated whether and how TLR-4 influences IL-8 expression in VSMCs. Exposure of aortic smooth muscle cells to TLR-4 agonistic lipopolysaccharide (LPS) not only enhanced release of IL-8 protein but also induced IL-8 gene transcript via promoter activation. The LPS-induced activation of IL-8 promoter was attenuated by dominant-negative MKK1, but not by dominant-negative MKK3. The promoter activation was also impaired by dominant negative CCAAT/enhancer binding protein (C/EBP), IkappaB, and dominant negative c-Jun. In comparison with the mutation of the AP-1 binding site, the mutation of NF-kappaB site and C/EBP binding site in the IL-8 promoter region more significantly impaired the promoter activation. Moreover, both promoter activity and release of IL-8 were inhibited by U0126 and curcumin, but not by SB202190, epigallocatechin 3-gallate and resveratrol. The present study reports that TLR-4-agonistic LPS upregulates IL-8 at the transcriptional and post-translational level in VSMCs, and that ERK1/2, NF-kappaB, and C/EBP play major roles in the upregulation of IL-8.

Quercetin regulates Th1/Th2 balance in a murine model of asthma.

Quercetin is found to be the most active of the flavonoids in studies and many medicinal plants owe much of their activity to their high Quercetin content. Quercetin has demonstrated significant anti-inflammatory activity because of direct inhibition of several initial processes of inflammation. However, its anti-allergic effect in the Th1/Th2 immune response was poorly understood. Recently, it was shown that T-bet and GATA-3 were master Th1 and Th2 regulatory transcription factors. In this study, we have attempted to determine whether Quercetin regulates Th1/Th2 cytokine production, T-bet and GATA-3 gene expression in OVA-induced asthma model mice. Quercetin reduced the increased levels of IL-4, Th2 cytokine production in OVA-sensitized and -challenged mice. The other side, it increased IFN-gamma, Th1 cytokine production in Quercetin administrated mice. We also examined to ascertain whether Quercetin could influence Eosinophil peroxidase (EPO) activity. The administration of Quercetin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, this study may provide evidence that Quercetin plays a critical role in the amelioration of the pathogenetic process of asthma in mice. These findings provide new insight into the immunopharmacological role of Quercetin in terms of its effects in a murine model of asthma, and also broaden current perspectives in our understanding of the immunopharmacological functions of Quercetin.

Epigallocatechin-3-gallate protects toluene diisocyanate-induced airway inflammation in a murine model of asthma.

Epigallocatechin-3-gallate (EGCG), a major form of tea catechin, has anti-allergic properties. To elucidate the anti-allergic mechanisms of EGCG, we investigated its regulation of matrix metalloproteinase (MMP-9) expression in toluene diisocyanate (TDI)-inhalation lung tissues as well as TNF-alpha and Th2 cytokine (IL-5) production in BAL fluid. Compared with untreated asthmatic mice those administrated with EGCG had significantly reduced asthmatic reaction. Also, increased reactive oxygen species (ROS) generation by TDI inhalation was diminished by administration of EGCG in BAL fluid. These results suggest that EGCG regulates inflammatory cell migration possibly by suppressing MMP-9 production and ROS generation, and indicate that EGCG may be useful as an adjuvant therapy for bronchial asthma.