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This study investigated the properties of Latilactobacillus curvatus MS2 isolated from Korean traditional fermented seafood as probiotics and the effect of reducing cholesterol as a synbiotic with isomalto-oligosaccharide (IMO) in BALB/c mice. The isolated strain showed high resistance to acids and bile acids and exhibited a high DPPH scavenging capacity of 72.27 ± 0.38 %. In the intestinal adhesion test using HT-29 cells, the adhesion rate of MS2 was 17.10 ± 1.78 %, which was higher than the adhesion rate of the other investigated probiotics. MS2 showed good antimicrobial activity against food-borne pathogens, especially Staphylococcus aureus , S. epidermidis , Escherichia coli , and Vibrio vulnificus. This strain had high availability for IMO among the prebiotics of fructo-oligosaccharide, inulin and IMO. Oral administration of MS2 and IMO to BALB/c mice for 5 weeks resulted in a significant reduction in blood cholesterol levels by regulating liver lipid metabolism. These results suggest that the combination of MS2 and IMO has potential for application in functional foods. [Display omitted] • The probiotic properties of Latilactobacillus curvatus MS2 were investigated. • Dietary supplementation of MS2 downregulated the blood cholesterol levels. • Supplementation with MS2 maintained the intestinal microbial balance of BALB/c mice. [ABSTRACT FROM AUTHOR]

• A novel metagrating for simultaneous realization of mode-converting and anomalous steering of elastic wave reflection is proposed. • Near-perfect mode-conversion efficiencies are achieved for in-plane waves in thin elastic plate. • Metagratings realize longitudinal-to-shear and shear-to-longitudinal wave mode conversions in scattered refection field. • Higher-order scattered diffraction modes are effectively and selectively suppressed in metagratings. Metasurfaces have recently received much attentions for manipulating waves. However, it is difficult to control all high-order or diffracted modes using the popularly employed metasurfaces. Herein, we propose a new way for converting a normally incident elastic longitudinal (or shear) wave mode to an obliquely reflected elastic shear (or longitudinal) one, using metagratings of elaborately designed and arranged strips. For a longitudinal (or shear) wave incidence upon the free end of an elastic plate, it is intrinsically difficult to realize full-power mode conversion and steer the converted mode without generating undesired reflected waves. We show that our elaborately designed and optimized multiple rectangular strip-type metagratings are effective in simultaneously fulfilling the mode conversion and anomalous steering of elastic waves. Unlike metasurfaces, the proposed metagratings operate via the diffraction theory and multiple rectangular strips permit sufficient design freedom to fulfill the two design objectives. Several numerical simulations in this work show that the proposed strip-type metagratings achieve near-perfect mode-conversion efficiencies reaching 96 %, and the performance is supported by experiments. Applications of the designed metagratings in nondestructive evaluation are also demonstrated. [ABSTRACT FROM AUTHOR]

Avian influenza (AI) is an economically-important disease of poultry worldwide. The use of vaccines to control AI has increased because of frequent outbreaks of the disease in endemic countries. Newcastle disease virus (NDV) vectored vaccine has shown to be effective in protecting chickens against a highly pathogenic avian influenza virus (HPAIV) infection. However, preexisting antibodies to NDV vector might affect protective efficacy of the vaccine in the field. As an alternative strategy, we evaluated vaccine efficacy of a chimeric NDV vectored vaccine in which the ectodomains of F and HN proteins were replaced by those of avian paramyxovirus serotype-2. The chimeric NDV vector stably expressed the HA protein in vivo , did not cross-react with NDV, was attenuated to be used as a safe vaccine, and provided a partial protection of 1-day-old immunized chickens against HPAIV subtype H5N1challenge, indicating its potential use for early protection of chickens. [ABSTRACT FROM AUTHOR]

Objective: To estimate the percentage of infants with large birth size attributable to excess gestational weight gain (GWG), independent of prepregnancy body mass index, among mothers with preexisting diabetes mellitus (PDM).Study Design: We analyzed 2004-2008 Florida linked birth certificate and maternal hospital discharge data of live, term (37-41weeks) singleton deliveries (N=641,857). We calculated prevalence of large-for-gestational age (LGA) (birth weight-for-gestational age≥90th percentile) and macrosomia (birth weight>4500g) by GWG categories (inadequate, appropriate, or excess). We used multivariable logistic regression to estimate the relative risk (RR) of large birth size associated with excess compared to appropriate GWG among mothers with PDM. We then estimated the population attributable fraction (PAF) of large birth size due to excess GWG among mothers with PDM (n=4427).Results: Regardless of diabetes status, half of mothers (51.2%) gained weight in excess of recommendations. Large birth size was higher in infants of mothers with PDM than in infants of mothers without diabetes (28.8% versus 9.4% for LGA, 5.8% versus 0.9% for macrosomia). Among women with PDM, the adjusted RR of having an LGA infant was 1.7 (95% CI 1.5, 1.9) for women with excess GWG compared to those with appropriate gain; the PAF was 27.7% (95% CI 22.0, 33.3). For macrosomia, the adjusted RR associated with excess GWG was 2.1 (95% CI 1.5, 2.9) and the PAF was 38.6% (95% CI 24.9, 52.4).Conclusion: Preventing excess GWG may avert over one-third of macrosomic term infants of mothers with PDM. Effective strategies to prevent excess GWG are needed. [ABSTRACT FROM AUTHOR]

The potential use of induced pluripotent stem cells (iPSCs) in personalized regenerative medicine applications may be augmented by transgenics, including the expression of constitutive cell labels, differentiation reporters, or modulators of disease phenotypes. Thus, there is precedence for reproducible transgene expression amongst iPSC sub-clones with isogenic or diverse genetic backgrounds. Using virus or transposon vectors, transgene integration sites and copy numbers are difficult to control, and nearly impossible to reproduce across multiple cell lines. Moreover, randomly integrated transgenes are often subject to pleiotropic position effects as a consequence of epigenetic changes inherent in differentiation, undermining applications in iPSCs. To address this, we have adapted popular TALEN and CRISPR/Cas9 nuclease technologies in order to introduce transgenes into pre-defined loci and overcome random position effects. AAVS1 is an exemplary locus within the PPP1R12C gene that permits robust expression of CAG promoter-driven transgenes. Gene targeting controls transgene copy number such that reporter expression patterns are reproducible and scalable by ∼2-fold. Furthermore, gene expression is maintained during long-term human iPSC culture and in vitro differentiation along multiple lineages. Here, we outline our AAVS1 targeting protocol using standardized donor vectors and construction methods, as well as provide practical considerations for iPSC culture, drug selection, and genotyping. [ABSTRACT FROM AUTHOR]

Dopamine–melanin nanospheres are promising materials for photoprotection, structural coloration, and thermoregulation due to their unusual optical and chemical properties. Here, we report the experimental parameters which influence size of dopamine–melanin nanospheres and uniformity. Dopamine precursors are oxidatively polymerized in basic aqueous medium. Therefore, concentration of hydroxide ions significantly influences reaction rate and size of nanospheres. To investigate the effect of hydroxide ions, we adjust three different parameters which affect pH of medium: concentration of sodium hydroxide and dopamine hydrochloride, and reaction temperature. At constant temperature, concentration of hydroxide ions is linearly proportional to initial reaction rates which determine the number of nuclei for nanosphere growth. Temperature alters not only initial reaction rate but also diffusivity of molecules, leading to deviation from the relation between the reaction rate and the number of nuclei. The diameter of dopamine–melanin nanospheres can be readily controlled in a range of 80–490 nm through adjusting concentration of dopamine precursor, while maintaining uniform-size distribution and dispersion stability. The synthesized nanospheres are analyzed to confirm the chemical structure, which is composed of approximately 6 indole units. Moreover, surface and chemical properties of the nanospheres are characterized to provide valuable information for surface modification and application. [ABSTRACT FROM AUTHOR]

Noroviruses are the most common cause of acute gastroenteritis in humans. Development of an effective vaccine is required for reducing their outbreaks. In order to develop a GI norovirus vaccine, Newcastle disease virus vectors, rLaSota and modified rBC, were used to express VP1 protein of Norwalk virus. Co-expression of VP1 and VP2 proteins by Newcastle disease virus vectors resulted in enhanced expression of Norwalk virus VP1 protein and self-assembly of VP1 protein into virus-like particles. Furthermore, the Norwalk virus-specific IgG response induced in mice by Newcastle disease virus vectors was similar to that induced by baculovirus-expressed virus-like particles in mice. However, the modified rBC vector in the presence of VP2 protein induced significantly higher levels of cellular and mucosal immune responses than those induced by baculovirus-expressed VLPs. These results indicate that Newcastle disease virus has great potential for developing a live Norwalk virus vaccine by inducing humoral, cellular and mucosal immune responses in humans. [ABSTRACT FROM AUTHOR]

This study describes a new and sensitive method for measuring the in vivo and in vitro cytotoxicity of 2 earthworm species, Eisenia andrei and Perionyx excavatus , exposed to copper. Specifically, we measured the number of coelomocyte cells that were affected by copper following in viv o and in vitro exposure by flow cytometry, after calcein acetoxymethyl ester (calcein-AM) staining. We found that the coelomocyte viability of both earthworm species was noticeably reduced in the in vivo cytotoxicity test at concentrations of 100 mg/kg copper in dry soil. However, pathological symptoms, such as mucous secretion and bleeding, swelling, thinning, and fragmentation, and burrowing symptoms were not evident following exposure to copper levels of <400 mg/kg dry soil. In conclusion, the present study demonstrates that calcein-AM is a more sensitive test of earthworm coelomocyte cytotoxicity compared to the traditional individual level toxicity test. Therefore, this test could be used to detect low levels of metal contamination in soils. [ABSTRACT FROM AUTHOR]

Highlights: [•] We introduce new capillary microfluidic geometry for the creation of double-emulsion drops. [•] High inertia leads to insertion of a drop into a drop injected, forming double-emulsion drops. [•] Mechanism by which double-emulsion drops form is studied with Weber number. [•] Polymersomes encapsulating a continuous phase are prepared from double-emulsion drops. [Copyright &y& Elsevier]

Abstract: Multistate outbreaks of Escherichia coli O157:H7 infections through consumption of contaminated foods including produce products have brought a great safety concern. The objectives of this study were to determine the effect of biofilm and quorum sensing production on the attachment of E. coli O157:H7 on food contact surfaces and to evaluate the transfer of the pathogen from the food contact to various food products. E. coli O157:H7 produced maximum levels of AI-2 signals in 12h of incubation in tested meat, poultry, and produce broths and subsequently formed strong biofilm in 24h of incubation. In general, E. coli O157:H7 formed stronger biofilm on stainless steel than glass. Furthermore, E. coli O157:H7 that had attached on the surface of stainless steel was able to transfer to meat, poultry, ready-to-eat deli, and produce products. Strong attachment of the transferred pathogen on produce products (cantaloupe, lettuce, carrot, and spinach) was detected (>103 CFU/cm2) even after washing these products with water. Our findings suggest that biofilm formation by E. coli O157:H7 on food contact surfaces can be a concern for efficient control of the pathogen particularly in produce products that require no heating or cooking prior to consumption. [Copyright &y& Elsevier]

Compassion is closely associated with prosocial behavior. Although there is growing interest in developing strategies that cultivate compassion, most available strategies rely on effortful reflective processes. Furthermore, few studies have investigated neurocognitive mechanisms underlying compassion-dependent improvement of prosocial responses. We devised a novel implicit compassion promotion task that operates based on association learning and examined its prosocial effects in two independent experiments. In Experiment 1, healthy adults were assigned to either the compassion or control group. For the intervention task, the compassion group completed word fragments that were consistently related to compassionate responses toward others; in contrast, the control group completed word fragments related to emotionally neutral responses toward others. Following the intervention task, we measured attentional biases to fearful, sad, and happy faces. Prosocial responses were assessed using two measures of helping: the pen-drop test and the helping intentions rating test. In Experiment 2, independent groups of healthy adults completed the same intervention tasks used in Experiment 1. Inside a functional MRI scanner, participants rated empathic care and distress based on either distressful or neutral video clips. Outside the scanner, we assessed the degree of helping intentions toward the victims depicted in the distressful clips. The results of Experiment 1 showed that the compassion promotion task reduced attentional vigilance to fearful faces, which in turn mediated a compassion promotion task-dependent increase in helping intentions. In Experiment 2, relative to the control group, the compassion group showed reduced empathic distress and increased activity in the medial orbitofrontal cortex in response to others' suffering. Furthermore, increased functional connectivity of the medial orbitofrontal and inferior parietal cortex, predicted by reduced empathic distress, explained the increase in helping intentions. These results suggest the potential of implicit compassion promotion intervention to modulate compassion-related and prosocial responses as well as highlight the brain activation and connectivity related to these responses, contributing to our understanding of the neurocognitive mechanisms underlying compassion-dependent prosocial improvement. [ABSTRACT FROM AUTHOR]

• A novel elastic metagrating model is proposed for efficient realization of anomalous steering of elastic waves. • The first and higher-order scattered longitudinal waves are selectively suppressed or preserved. • An analytic model is established for the proposed beam-type metagratings and coupled with elastic waves in a continuum. • The effective manipulation of anomalous reflections and beam steering of elastic longitudinal waves is demonstrated. • The physics related to the present metagratings is explored and experimental validation is performed. Metagratings have recently received much attention for effective realization of anomalous wave steering. Governed by the diffraction grating theory and the concept of metamaterials, metagratings allow to suppress superfluous propagations of high-order scattering modes in a selective manner such that wavefronts are accurately steered as designated. While numerous metagratings have been reported in electromagnetic wave research field, little has been explored in the elastic wave regime because of difficulties caused by complicatedly coupled motions among various types of elastic waves. In this circumstance, we newly propose a novel elastic metagrating model to realize anomalous steering of longitudinal waves in elastic continuum medium. Modeled by a periodic arrangement of a single or array of so-called beam-type elastic members, the present elastic metagratings resolve the difficulties in steering a specific scattered mode of elastic longitudinal waves by suppressing undesired modes in the scattered wave field. As the metagratings are attached to a boundary of elastic continuum, both longitudinal and flexural motions in the beam-type members are so coupled with elasticity wave solutions in the elastic medium as to thoroughly manipulate the reflected longitudinal waves from the interface. A set of appropriate geometric parameters of the beam-type members are searched for a direct control of the scattered modes quantitatively. As practical applications, the proposed elastic metagratings are applied to realize anomalous reflections and asymmetric splitting of longitudinal elastic waves. As well as experimental verifications, performance of the designed elastic metagratings are physically interpreted in the perspective of phase modulation. [ABSTRACT FROM AUTHOR]

[Display omitted] Microcapsules with osmotically-inflated elastic shells exhibit an ultrafast release of encapsulants while mechanically stimulating the microenvironments, akin to popping balloons. To prepare elastic shells with uniform thickness and size, monodisperse water-in-oil-in-water (W/O/W) double-emulsion drops are produced in a capillary microfluidic device. The polydimethylsiloxane (PDMS)-containing oil phase is thermally cured to create the elastic shell. The elastic shells are inflated by pumping water into the lumen in hypotonic conditions. The inflated microcapsules produced undergo mechanical compression, and their release properties are studied. By controlling the osmotic pressure difference, Microballoons are inflated into a diameter of 200 μm – 316 μm and shell thickness of 7.8 μm – 0.7 µm, respectively. The inflated shell pops due to mechanical failure when subjected to mechanical stress above a certain threshold, resembling a balloon. During popping, the stretched shell rapidly retracts to the original uninflated state, resulting in an ultrafast release of encapsulants from the lumen within a millisecond. This process converts elastic potential energy stored in the shell into mechanical energy with substantial power. The microballoons mechanically stimulate the local environment, leading to the direct and rapid release of encapsulants. This has the potential to improve absorption efficiency. [ABSTRACT FROM AUTHOR]

Withaferin A, a withanolide derived from the medicinal plant Withania somnifera , has been reported to exhibit anti-tumorigenic activity against various cancer cells. In this study, we show that withaferin A inhibits the constitutive and recombinant human growth-arrest-specific protein 6 (rhGas6)-induced phosphorylation of Axl and STAT3. In addition, withaferin A also induces the down-regulation of Axl protein expression in a lysosome-dependent manner and inhibits rhGas6-induced wound healing and cell migration. Furthermore, the overexpression of Axl attenuates withaferin A-induced apoptosis. Taken together, the data from the present study indicate that the withaferin A-mediated down-regulation of the Gas6/Axl signaling pathway mediates the inhibition of cell migration and the induction of apoptosis. [ABSTRACT FROM AUTHOR]

Abstract: Transforming growth factor-β1 (TGF-β1) performs diverse cellular functions, including anti-inflammatory activity. The inhibitory Smad (I-Smad) Smad6 was previously shown to play an important role in TGF-β1-induced negative regulation of Interleukin-1/Toll-like receptor (IL-1R/TLR) signaling through binding to Pellino-1, an adaptor protein of interleukin-1 receptor associated kinase 1(IRAK1). However, it is unknown whether Smad7, the other inhibitory Smad, also has a role in regulating IL-1R/TLR signaling. Here, we demonstrate that endogeneous Smad7 and Smad6 simultaneously bind to discrete regions of Pellino-1 upon TGF-β1 treatment, via distinct regions of the Smad MH2 domains. In addition, the Smad7-Pellino-1 interaction abrogated NF-κB activity by blocking formation of the IRAK1-mediated IL-1R/TLR signaling complex, subsequently causing reduced expression of pro-inflammatory genes. Double knock-down of endogenous Smad6 and Smad7 genes by RNA interference further reduced the anti-inflammatory activity of TGF-β1 than when compared with single knock-down of Smad7. These results provide evidence that the I-Smads, Smad6 and Smad7, act as critical mediators for effective TGF-β1-mediated suppression of IL-1R/TLR signaling, by simultaneous binding to discrete regions of Pellino-1. [Copyright &y& Elsevier]

Abstract: In this paper, we report the preparation of binary clusters of colloidal particles with different sizes or species into complex structures using oil-in-water emulsion droplets as confining geometries. First, polystyrene or silica particles with bimodal size distribution were packed densely by evaporation-induced self-assembly inside oil-in-water emulsion droplets. The configurations of larger particles inside the droplets minimize the second moment of the particle locations for the ratio of large to small particle sizes less than 3. Also, the configurations of bimodal clusters were predicted by using a surface evolver simulation, and the simulation predictions were compared with the experimental results. In addition, heterogeneous colloidal clusters were produced by emulsifying the binary mixture suspension of polystyrene and silica particles in aqueous medium followed by evaporating the oil phase. A density gradient centrifugation was applied to fractionate the asymmetric binary dimers comprised of PS and silica microspheres. [Copyright &y& Elsevier]

Chronic infection with mycobacteria is controlled by the formation of granulomas. The failure of granuloma maintenance results in reactivation of disease. Macrophages are the dominant cell type in granulomas, but CD4+ T cells are the master organizers of granuloma structure and function. Recent work points to an unrecognized role for nonspecific T cells in maintaining granuloma function in the chronic phase of infection. In addition, it has become clear that mycobacteria and host T cells collaborate in formation of granulomas. Further understanding of how nonspecific T cells contribute to granuloma formation, as well as how bacteria and T cells maintain a harmonious relationship over the life of the host, will facilitate the development of new strategies to treat mycobacterial disease. [Copyright &y& Elsevier]

Human mesenchymal stem cells (MSCs) are known to have anti-inflammatory and immunomodulatory functions; thus, several MSC products have been applied as cell therapy in clinical trials worldwide. Recent studies have demonstrated that MSC spheroids have superior anti-inflammatory and immunomodulatory functions to a single cell suspension. Current methods to prepare MSC spheroids include hanging drop, concave microwell aggregation, spinner flask, and gravity circulation. However, all these methods have limitations such as low scalability, easy cell clumping, low viability, and irregular size distribution. Here, we present a nano-patterned culture plasticware named PAMcell™ 3D plate to overcome these limitations. Nano-sized silica particles (700 nm) coated with RGD peptide were arrayed into fusiform onto the PLGA film. This uniform array enabled the seeded MSCs to grow only on the silica particles, forming uniform-sized semi-spheroids within 48 h. These MSC spheroids have been shown to have enhanced stemness, anti-inflammatory, and immunomodulatory functions, as revealed by the increased expression of stem cell markers (Oct4, Sox2, and Nanog), anti-inflammatory (IL-10, TSG6, and IDO), and immunomodulatory molecules (HGF, VEGF, CXCR4) both at mRNA and protein expression levels. Furthermore, these MSC spheroids demonstrated an increased palliative effect on glycemic control in a multiple low-dose streptozotocin-induced diabetes model compared with the same number of MSC single cell suspensions. Taken together, this study presents a new method to produce uniform-sized MSC spheroids with enhanced anti-inflammatory and immunomodulatory functions in vitro and in vivo. • Mesenchymal stem cells have anti-inflammatory and immunomodulatory functions. • 3D MSC spheroids have superior anti-inflammatory and immunomodulatory functions to 2D monolayer cells. • MSC spheroids formed on a new culture device named PAMcell™ have enhanced functions in vitro and in vivo. [ABSTRACT FROM AUTHOR]

A glucagon-like peptide 1 receptor agonist (GLP-1 RA) semaglutide was approved for the treatment of obesity by the Food and Drug Administration. However, it can cause gastrointestinal events at high doses, limiting its broader use. Combining drugs with multiple mechanisms of action could enhance the weight-reducing effects while minimizing side effects. To this end, we investigated the combined effects of semaglutide and avasimibe, an acyl-CoA:cholesterol acyltransferase 1 (ACAT1) inhibitor, on weight reduction in diet-induced obesity mice. Two cohorts of mice were used: In cohort 1, mice were fed a high-fat (HF) diet for 12 weeks and then randomly assigned to the vehicle, avasimibe [10 mg/kg body weight (BW)], semaglutide (0.4 mg/kg BW), or combination groups. The drugs were administered via subcutaneous (sc) injections on a daily basis. In cohort 2, mice were fed an HF diet for 8 weeks and randomly assigned to the same four groups, but avasimibe was administered at a dose of 20 mg/kg BW, and the drugs were administered every 3 days. In cohort 1, semaglutide initially reduced food intake initially, but this effect was diminished with prolonged administration. Avasimibe, on the other hand, did not affect food intake but prevented weight gain to a lesser extent than semaglutide. Importantly, the combination treatment resulted in the greatest percentage of body weight reduction, along with lower plasma glucose and leptin levels compared to the semaglutide single-treatment group. Cohort 2 confirmed that the superior weight loss in the combination group compared to the other three groups was largely due to a significant reduction in fat mass. Histological analysis of inguinal adipose tissue showed smaller adipocyte size across all treatment groups compared to the vehicle group, with no significant differences among the treatment groups. Collectively, these findings suggest combining semaglutide and avasimibe could be an effective approach to weight management. • Combined semaglutide and avasimibe reduces body weight and food intake in DIO mice. • Combined semaglutide and avasimibe reduces plasma cholesterol and leptin levels. • Combined semaglutide and avasimibe reduces fat mass and adipocyte size in DIO mice. [ABSTRACT FROM AUTHOR]

Highlights • In the highlights, have performed to examine the function of individual oligosaccharide chains in signal transduction. • Produced recombinant eelFSH mutants (wild type, β/αΔ56, β/αΔ79, β/αΔ56.79, and βΔ5/α) in CHO cells. • Revealed the site-specific roles of eelFSH carbohydrate residues through eelFSH receptor. Abstract Eel follicle-stimulating hormone (eelFSH) is composed of a common α-subunit and a hormone specific β-subunit, both of which contain two N -linked carbohydrate residues. We characterized the biologically active single chains by fusing the α-subunit to the carboxyl terminal region of the eelFSH β-subunit. Expression vectors were constructed and the biological activity of the recombinant hormones (rec-hormones) was characterized using Chinese hamster ovary (CHO) K1 cells expressing the eelFSH receptor gene. Mutagenesis of the individual and double glycosylated sites was performed to determine the functions of the oligosaccharide chains on signal transduction. The absence of the Asn22 (eelFSHβΔ22/α) and Asn5.22 (eelFSHβΔ5.22/α) N -linked oligosaccharide chain in the eelFSH β-subunit completely reduced the secretion level in the medium and cell lysate of CHO-K1 cells. The expression levels of eelFSHβ/α wild-type in CHO suspension (CHO-S) cells was approximately 4-fold higher in CHO-k1 cells. The molecular weight of rec-eelFSHβ/α wild-type by western blotting analysis was found to be 34 kDa. Mutants (β/αΔ56, β/αΔ79, and βΔ5/α) lacking single oligosaccharide sites showed molecular weights that were reduced by approximately 10%. The digestion of N-linked oligosaccharides using PNGaseF treatment showed that the molecular weights of all mutants were reduced to 27-kDa. The oligosaccharide chains in rec-eelFSHβ/α wild-type were modified to a molecular weight of approximately 7–10 kDa in CHO-K1 and CHO-S cells. Oligosaccharide site deletions at positions Asn56 and Asn79 on the α-subunit and Asn5 on the β-subunit were found to play an essential role in cAMP signal transduction through the eelFSH receptor. The EC 50 values of Asn56 and Asn5 resulted in a significant decrease in potency to 64% and 53% of the wild type, respectively. Specifically, the removal of the carbohydrates at Asn79 of the α-subunit (β/αΔ79) was drastically reduced to 53.8% of the wild-type levels in maximum response. These results have allowed for the identification of the site-specific roles of carbohydrate residues in eel FSH. Our data suggest that N -linked oligosaccharide chains play a pivotal role in biological activity through the eelFSH receptor as suggested in similar studies of other mammalian FSH hormones. [ABSTRACT FROM AUTHOR]

Abstract Pseudomonas aeruginosa is an opportunistic human pathogen which exhibits its property of pathogenesis due to several factors, including the formation of biofilm and production of several virulence factors. Development of resistance properties against antibiotics leads to the discovery of certain alternative strategies to combat its pathogenesis. In the present study, a highly stable, biocompatible and water soluble nanocomposites (NCs) are synthesized from chitosan (CS) and the polypyrrole (PPy). The resultant chitosan-polypyrrole nanocomposites (CS-PPy NCs) inhibit the establishment of biofilm and also eradicate the preformed matured biofilm formed by P. aeruginosa. CS-PPy NCs inhibit the hemolytic and protease activities of P. aeruginosa. The NCs significantly reduce the production of many virulence factors such as pyocyanin, pyroverdine and rhamnolipid. CS-PPy NCs also suppress the bacterial motility such as swimming and swarming. The present study showed that highly stable CS-PPy NCs act as a potent antibiofilm and antivirulence drug for the treatment of P. aeruginosa infection. Graphical abstract Image 1 Highlights • CS-PPy is a water soluble and highly stable nanocomposites. • CS-PPy NCs inhibits the formation of biofilm of P. aeruginosa. • CS-PPy NCs exhibits antihemolytic and antivirulence properties to P. aeruginosa. • CS-PPy NCs impairs the motilities properties of P. aeruginosa. • CS-PPy NCs can be used as a potent antibiofilm and antivirulence drug. [ABSTRACT FROM AUTHOR]

Peroxiredoxins (Prdx) are thiol specific antioxidant enzymes that play a pivotal role in cellular oxidative stress by reducing toxic peroxide compounds into nontoxic products. In this study, we identified and characterized a peroxiredoxin 6 counterpart from Japanese eel ( Anguilla japonica ) (AjPrdx6) at molecular, transcriptional and protein level. The identified full-length coding sequence of AjPrdx6 (669 bp) coded for a polypeptide of 223 aa residues (24.9 kDa). Deduced protein of AjPrdx6 showed analogy to characteristic structural features of 1-cysteine peroxiredoxin sub-family. According to the topology of the generated phylogenetic reconstruction AjPrdx6 showed closest evolutionary relationship with Salmo salar . As detected by Quantitative real time PCR (qPCR), AjPrdx6 mRNA was constitutively expressed in all the tissues examined. Upon the immune challenges with Edwardsiella tarda , lipopolysaccharides and polyinosinic:polycytidylic acid, expression of AjPrdx6 mRNA transcripts were significantly induced. The general functional properties of Prdx6 were confirmed using purified recombinant AjPrdx6 protein by deciphering its potent protective effects on cultured vero cells (kidney epithelial cell from an African green monkey) against H 2 O 2 -induced oxidative stress and protection against oxidative DNA damage elicited by mixed function oxidative (MFO) system. Altogether, our findings suggest that AjPrdx6 is a potent antioxidant protein in Japanese eels and its putative immune relevancy in pathogen stress mounted by live-bacteria or pathogen associated molecular patterns (PAMPs). [ABSTRACT FROM AUTHOR]

Lipocalin-2 (LCN2) is a member of the lipocalin superfamily and plays a critical role in the regulation of various physiological processes, such as inflammation and obesity. In this study, we report that LCN2 negatively modulates the proliferation and differentiation of osteoclast precursors, resulting in impaired osteoclast formation. The overexpression of LCN2 in bone marrow-derived macrophages or the addition of recombinant LCN2 protein inhibits the formation of multinuclear osteoclasts. LCN2 suppresses macrophage colony-stimulating factor (M-CSF)-induced proliferation of osteoclast precursor cells without affecting their apoptotic cell death. Interestingly, LCN2 decreases the expression of the M-CSF receptor, c-Fms, and subsequently blocks its downstream signaling cascades. In addition, LCN2 inhibits RANKL-induced osteoclast differentiation and attenuates the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1), which are important modulators in osteoclastogenesis. Mechanistically, LCN2 inhibits NF-κB signaling pathways, as demonstrated by the suppression of IκBα phosphorylation, nuclear translocation of p65, and NF-κB transcriptional activity. Thus, LCN2 is an anti-osteoclastogenic molecule that exerts its effects by retarding the proliferation and differentiation of osteoclast lineage cells. [ABSTRACT FROM AUTHOR]

Abstract: In order to guarantee both performance and programmability demands in 3D graphics applications, vector and multithreaded SIMD architectures have been employed in recent graphics processing units. This paper introduces a novel instruction-systolic array architecture, which transfers an instruction stream in a pipelined fashion to efficiently share the expensive functional resources of a graphics processor. Specifically, cache misses and dynamic branches can cause additional latencies and complicated management in these parallel architectures. To address this problem, we combine a systolic execution scheme with on-demand warp activation that handles cache miss latency and branch divergence efficiently without significantly increasing hardware resources, either in terms of logic or register space. Simulation indicates that the proposed architecture offers 25% better performance than a traditional SIMD architecture with the same resources, and requires significantly fewer resources to match the performance of a typical modern vector multi-threaded GPU architecture. [Copyright &y& Elsevier]

Abstract: Here, we first demonstrated the neuroprotective effect of acupuncture after SCI. Acupuncture applied at two specific acupoints, Shuigou (GV26) and Yanglingquan (GB34) significantly alleviated apoptotic cell death of neurons and oligodendrocytes, thereby leading to improved functional recovery after SCI. Acupuncture also inhibited caspase-3 activation and reduced the size of lesion cavity and extent of loss of axons. We also found that the activation of both p38 mitogen-activated protein kinase and resident microglia after injury are significantly attenuated by acupuncture. In addition, acupuncture significantly reduced the expression or activation of pro-nerve growth factor, proinflammatory factors such as tumor necrosis factor-α, interleukin-1β, interleukin-6, nitric oxide synthase, cycloxygenase-2, and matrix metalloprotease-9 after SCI. Thus, our results suggest that the neuroprotection by acupuncture may be partly mediated via inhibition of inflammation and microglial activation after SCI and acupuncture can be used as a potential therapeutic tool for treating acute spinal injury in human. [Copyright &y& Elsevier]

Abstract: Dysregulation of transforming growth factor-β (TGF-β) signaling has been implicated in the pathogenesis of a variety of diseases including cancer; therefore, pharmacological inhibitors that target the TGF-β signaling pathway might be promising drugs for disease therapy. In this study, we investigated the mechanism of inhibition of TGF-β signaling by the Hsp90 inhibitor geldanamycin (GA). Treatment with GA suppressed TGF-β signaling, as evidenced by inhibition of TGF-β-induced phosphorylation and transcriptional activity of Smad3 and decreased induction of target genes. Western blot analysis revealed that GA induced degradation of TGF-β type I and type II receptors through a proteasome-dependent pathway. Notably, induction of Hsp70 by GA correlated with inhibition of TGF-β signaling. Suppression of Hsp70 expression by Hsp70 siRNA or KNK437, an inhibitor of Hsp70 synthesis, blocked the inhibition of TGF-β signaling by GA. Furthermore, Hsp70 interacted directly with TGF-β receptors following GA treatment. Our results suggest that GA-mediated induction of Hsp70 and its subsequent interaction with TGF-β receptors plays a crucial role in inhibition of TGF-β signaling. [Copyright &y& Elsevier]

Abstract: Objective: To estimate the prevalence of gestational diabetes mellitus (GDM) prevalence estimates for subgroups of US Asian and Pacific Islander (API) women by using data from 2005 and 2006 birth certificates. Methods: Using 2005–2006 natality files from states that implemented the revised 2003 US birth certificate, which differentiates between GDM and preexisting diabetes (2005: 12 states; 2006: 19 states), we calculated age-adjusted GDM prevalence estimates for API mothers who delivered singleton infants. Results: Among 3,108,877 births, US APIs had a substantially higher age-adjusted prevalence of GDM (6.3%) than whites (3.8%), blacks (3.5%), or Hispanics (3.6%). Among API subgroups, age-adjusted GDM prevalence varied significantly, from 3.7% among women of Japanese descent to 8.6% among women of Asian Indian descent. Foreign-born APIs had significantly higher GDM rates than US-born APIs except among women of Japanese and Korean ancestry. Conclusion: Overall, US API women have the highest risk for GDM among all US racial/ethnic groups. However, APIs are a heterogeneous group by genetic background, culture, and diet and other lifestyle behaviors. Our findings imply that, whenever possible, API subgroups should be evaluated separately in health research. [Copyright &y& Elsevier]

Abstract: We investigated the effects of a novel peroxisome proliferator-activated receptor γ (PPARγ) agonist, KR62776, on osteoclast differentiation and function, and on the underlying signaling pathways. KR62776 markedly suppressed differentiation into osteoclasts in various osteoclast model systems, including bone marrow mononuclear (BMM) cells and a co-culture of calvarial osteoblasts and BMM cells. KR62776 suppressed the activation of tartrate-resistant acid phosphatase (TRAP) and the expression of genes associated with osteoclast differentiation, such as TRAP, dendritic cell-specific transmembrane protein (DC-STAMP), and osteoclast-associated receptor (OSCAR). Furthermore, KR62776 reduced resorption pit formation in osteoclasts, and down-regulated genes essential for osteoclast activity, such as Src and αvβ3 integrin. An analysis of a signaling pathway showed that KR62776 inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced activation of p38 mitogen-activated protein kinase (p38MAPK), extracellular regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and nuclear factor-κB (NF-κB). Together, these results demonstrate that KR62776 negatively affects osteoclast differentiation and activity by inhibiting the RANKL-induced activation of MAP kinases and NF-κB. [Copyright &y& Elsevier]

Abstract: In activated macrophage, large amounts of nitric oxide (NO) are generated by inducible nitric oxide synthase (iNOS), resulting in acute or chronic inflammatory disorders. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, 8-hydroxyquinoline (8HQ) inhibited the LPS-induced expression of both iNOS protein and mRNA in a parallel dose-dependent manner. 8HQ did not enhance the degradation of iNOS mRNA. To investigate the mechanism by which 8HQ inhibits iNOS gene expression, we examined the activation of MAP kinases in Raw 264.7 cells. We did not observe any significant change in the phosphorylation of MAPKs between LPS alone and LPS plus 8HQ-treated cells. Moreover, 8HQ significantly inhibited the DNA-binding activity of nuclear factor-κB (NF-κB) and CCAAT/enhancer-binding protein β (C/EBPβ), but not activator protein-1 and cAMP response element-binding protein. Taken together, these results suggest that 8HQ acts to inhibit inflammation through inhibition of NO production and iNOS expression through blockade of C/EBPβ DNA-binding activity and NF-κB activation. [Copyright &y& Elsevier]

Abstract: Phenolic compounds including tannins and flavonoids have been implicated in suppression of osteoclast differentiation/function and prevention of bone diseases. However, the effects of hydrolysable tannins on bone metabolism remain to be elucidated. In this study, we found that furosin, a hydrolysable tannin, markedly decreased the differentiation of both murine bone marrow mononuclear cells and Raw264.7 cells into osteoclasts, as revealed by the reduced number of tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells and decreased TRAP activity. Furosin appears to target at the early stage of osteoclastic differentiation while having no cytotoxic effect on osteoclast precursors. Analysis of the inhibitory mechanisms of furosin revealed that it inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced activation of p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK)/activating protein-1 (AP-1). Furthermore, furosin reduced resorption pit formation in osteoclasts, which was accompanied by disruption of the actin rings. Taken together, these results demonstrate that naturally occurring furosin has an inhibitory activity on both osteoclast differentiation and function through mechanisms involving inhibition of the RANKL-induced p38MAPK and JNK/AP-1 activation as well as actin ring formation. [Copyright &y& Elsevier]

Listeria monocytogenes is a food-borne pathogen present in various environmental reservoirs. It exhibits resistance and tolerance to antibiotics and sanitizing agents used in several food processing industries. It has been reported that L. monocytogenes chitinase can catalyze hydrolysis of chitin polymeric carbohydrate present in the environment and act as a virulence factor that support its survival in mammalian host cells. By taking advantage of chitinase, L. monocytogenes has both saprophytic and pathogenic lifestyles in the soil and the living host, respectively. The objective of the present study was to determine the involvement of chitin degradation products such as chitooligosaccharides (COS) in biofilm formation of L. monocytogenes. Results showed that different concentrations of COS with various molecular weight enhanced biofilm formation of L. monocytogenes. Such enhancement in biofilm formation contributed to the development of antibiotics resistance and disinfectants tolerance of cells present in the biofilm. The present article also described diverse roles of chitin, chitinase, and degradation of chitin and chitin-like substrates in saprophytic and pathogenic lifestyles of L. monocytogenes. This study offers a new direction for further exploration of the mechanisms of pathogenesis caused by L. monocytogenes. Image 1 • Chitin and its degradation products play important role in the lifecycles of L. monocytogenes. • COS enhance biofilm formation of Listeria monocytogenes. • The enhanced biofilm exhibits antibiotic resistance and disinfectant tolerance. • L. monocytogenes utilized COS as the sole carbon source for the growth. [ABSTRACT FROM AUTHOR]