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Feruloyl esterase (ferulic acid esterase, FAE) is an essential component of many biological processes in both eukaryotes and prokaryotes. This research aimed to investigate the role of FAE and its regulation mechanism in plant immunity. We identified a secreted feruloyl esterase VdFAE from the hemibiotrophic plant pathogen Verticillium dahliae. VdFAE acted as an important virulence factor during V. dahliae infection, and triggered plant defence responses, including cell death in Nicotiana benthamiana. Deletion of VdFAE led to a decrease in the degradation of ethyl ferulate. VdFAE interacted with Gossypium hirsutum protein dihydroflavanol 4‐reductase (GhDFR), a positive regulator in plant innate immunity, and promoted the degradation of GhDFR. Furthermore, silencing of GhDFR led to reduced resistance of cotton plants against V. dahliae. The results suggested a fungal virulence strategy in which a fungal pathogen secretes FAE to interact with host DFR and interfere with plant immunity, thereby promoting infection. [ABSTRACT FROM AUTHOR]

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Abstract Objective Compare and analyze clinical data of total laparoscopic pancreaticoduodenectomy (TLPD) cases for surgeons with / without first assistant experience (FAE) in TLPD. Probe influence of FAE in TLPD on the learning curve for an operator. Methods The clinical data of 239 patients, that underwent TLPD performed by two surgeons between January 2017 and January 2022) in our department, were consecutively collected and divided into two groups (A and B). Group A cases were operated by Surgeon A, with FAE of 57 TLPDs in our department prior to initial TLPD as an operator. Group B cases were operated by Surgeon B with no FAE of TLPD. Cumulative sum (CUSUM) method developed learning curves. Clinical data and both surgeons’ learning curves were statistically compared between both groups. Results Between both groups, no statistically significant variations were observed for pre-operative health conditions. Reduced surgical duration, blood loss and transfusion volume during surgery, together with reductions in major post–operative complication rates and reduced hospital/ICU stays were identified within Group A, having statistically significant variations. The technical plateau phases of the learning curves were approximately 25–41 cases and 35–51 cases, for Surgeon A and Surgeon B, respectively. Conclusion FAE in TLPD can accelerate the learning curve of TLPD for an operator, with safer surgical procedures and enhanced post–operative recovery.

Copyright of Ordnance Industry Automation is the property of Editorial Board for Ordnance Industry Automation and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Compare and analyze clinical data of total laparoscopic pancreaticoduodenectomy (TLPD) cases for surgeons with / without first assistant experience (FAE) in TLPD. Probe influence of FAE in TLPD on the learning curve for an operator. Methods: The clinical data of 239 patients, that underwent TLPD performed by two surgeons between January 2017 and January 2022) in our department, were consecutively collected and divided into two groups (A and B). Group A cases were operated by Surgeon A, with FAE of 57 TLPDs in our department prior to initial TLPD as an operator. Group B cases were operated by Surgeon B with no FAE of TLPD. Cumulative sum (CUSUM) method developed learning curves. Clinical data and both surgeons' learning curves were statistically compared between both groups. Results: Between both groups, no statistically significant variations were observed for pre-operative health conditions. Reduced surgical duration, blood loss and transfusion volume during surgery, together with reductions in major post–operative complication rates and reduced hospital/ICU stays were identified within Group A, having statistically significant variations. The technical plateau phases of the learning curves were approximately 25–41 cases and 35–51 cases, for Surgeon A and Surgeon B, respectively. Conclusion: FAE in TLPD can accelerate the learning curve of TLPD for an operator, with safer surgical procedures and enhanced post–operative recovery. [ABSTRACT FROM AUTHOR]

Fetal alcohol spectrum disorders (FASDs) are associated with systemic inflammation and neurodevelopmental abnormalities. Several candidate genes were found to be associated with fetal alcohol exposure (FAE)-associated behaviors, but a sex-specific complete transcriptomic analysis was not performed at the adult stage. Recent studies have shown that they are regulated at the developmental stage. However, the sex-specific role of RNA in FAE offspring brain development and function has not been studied yet. Here, we carried out the first systematic RNA profiling by utilizing a high-throughput transcriptomic (RNA-seq) approach in response to FAE in the brain cortex of male and female offspring at adulthood (P60). Our RNA-seq data analysis suggests that the changes in RNA expression in response to FAE are marked sex-specific. We show that the genes Muc3a, Pttg1, Rec8, Clcnka, Capn11, and pnp2 exhibit significantly higher expression in the male offspring than in the female offspring at P60. FAE female mouse brain sequencing data also show an increased expression of Eno1, Tpm3, and Pcdhb2 compared to male offspring. We performed a pathway analysis using a commercial software package (Ingenuity Pathway Analysis). We found that the sex-specific top regulator genes (Rictor, Gaba, Fmri, Mlxipl) are highly associated with eIF2 (translation initiation), synaptogenesis (the formation of synapses between neurons in the nervous system), sirtuin (metabolic regulation), and estrogen receptor (involved in obesity, aging, and cancer) signaling. Taken together, our transcriptomic results demonstrate that FAE differentially alters RNA expression in the adult brain in a sex-specific manner. [ABSTRACT FROM AUTHOR]

Fetal alcohol spectrum disorders (FASDs) are associated with systemic inflammation and neurodevelopmental abnormalities. Several candidate genes were found to be associated with fetal alcohol exposure (FAE)-associated behaviors, but a sex-specific complete transcriptomic analysis was not performed at the adult stage. Recent studies have shown that they are regulated at the developmental stage. However, the sex-specific role of RNA in FAE offspring brain development and function has not been studied yet. Here, we carried out the first systematic RNA profiling by utilizing a high-throughput transcriptomic (RNA-seq) approach in response to FAE in the brain cortex of male and female offspring at adulthood (P60). Our RNA-seq data analysis suggests that the changes in RNA expression in response to FAE are marked sex-specific. We show that the genes Muc3a, Pttg1, Rec8, Clcnka, Capn11, and pnp2 exhibit significantly higher expression in the male offspring than in the female offspring at P60. FAE female mouse brain sequencing data also show an increased expression of Eno1, Tpm3, and Pcdhb2 compared to male offspring. We performed a pathway analysis using a commercial software package (Ingenuity Pathway Analysis). We found that the sex-specific top regulator genes (Rictor, Gaba, Fmri, Mlxipl) are highly associated with eIF2 (translation initiation), synaptogenesis (the formation of synapses between neurons in the nervous system), sirtuin (metabolic regulation), and estrogen receptor (involved in obesity, aging, and cancer) signaling. Taken together, our transcriptomic results demonstrate that FAE differentially alters RNA expression in the adult brain in a sex-specific manner.

Abstract The follicle-associated epithelium (FAE) covering mucosa-associated lymphoid tissue is distinct from the villous epithelium in cellular composition and functions. Interleukin-22 binding protein (IL-22BP), provided by dendritic cells at the sub-epithelial dome region, inhibits the IL-22-mediated secretion of antimicrobial peptides by the FAE. The Notch signal from stromal cells underneath the FAE diminishes goblet cell differentiation. These events dampen the mucosal barrier functions to allow luminal microorganisms to readily gain access to the luminal surface of the FAE. Furthermore, receptor activator of nucleic factor-kappa B ligand (RANKL) from a certain stromal cell type induces differentiation into microfold (M) cells that specialize in antigen uptake in the mucosa. Microfold (M) cells play a key role in mucosal immune surveillance by actively transporting external antigens from the gut lumen to the lymphoid follicle. The molecular basis of antigen uptake by M cells has been gradually identified in the last decade. For example, GPI-anchored molecules (e.g., glycoprotein 2 (GP2) and cellular prion protein (PrPC)) and β1-integrin facilitate the transport of specific types of xenobiotics. The antigen transport by M cells initiates antigen-specific mucosal immune responses represented by the induction of secretory immunoglobulin A (S-IgA). Meanwhile, several invasive pathogens exploit M cells as a portal to establish a systemic infection. Recent findings have uncovered the molecular machinery of differentiation and functions of M cells.

Abstract Peyer's patches are known as the immune sensors of the intestine because of their ability to transport luminal antigens. The objective of this study was both to assess the prenatal and postnatal development of sheep ileal Peyer's patches with respect to histomorphology, distribution of CD4+ and CD8+ cells, and localization of proliferating and apoptotic cells, and to examine the morphology of M cells and expression of CK18 in follicle associated epithelium (FAE). We also hypothesized that CK18 could be a potential marker for M cell. Peyer's patches completed their histomorphological development in prenatal period and involuted in the postnatal period. The distribution of the CD4+ and CD8+ cells was similar in the last trimester of pregnancy (days 120–150) and the postnatal period, but differed in the early stages of foetal development (days 70–120). In the prenatal period, the follicular area displayed high levels of proliferation and apoptosis. We observed CK18 immunoreaction only in FAE. While M cells were devoid of microfolds in the early stages of the prenatal period, these cells acquired a prismatic shape and bore distinct apical microfolds in the late prenatal period and postnatal period. As a result, it was determined that, in sheep, the development of the ileal Peyer's patches occurred in the prenatal period, independent of exogenous antigenic stimulation, and in association with high levels of lymphopoiesis and apoptosis in the follicles. We found, for the first time, that CK18 is a novel and reliable marker for FAE in sheep ileal Peyer's patches. We suggest that CK18 positive cells in FAE are M cells. [ABSTRACT FROM AUTHOR]

Fetal alcohol spectrum disorders (FASD) are associated with social interaction behavior and gastrointestinal (GI) abnormalities. These abnormal behaviors and GI abnormalities overlap with autism spectrum disorder (ASD). We investigated the effect of fetal alcohol exposure (FAE) on social interaction deficits (hallmark of autism) in mice. Evidence indicates that exogenous lipopolysaccharide (LPS) administration during gestation induces autism-like behavior in the offspring. LPS regulates the expression of genes underlying differentiation, immune function, myelination, and synaptogenesis in fetal brain by the LPS receptor, TLR-4-dependent mechanism. In this study, we evaluated the role of TLR-4 in FAE-induced social behavior deficit. WT and TLR4-/- pregnant mice were fed Lieber-DeCarli liquid diet with or without ethanol. The control group was pair-fed with an isocaloric diet. Social behavior was tested in the adult offspring at postnatal day 60. Frontal cortex mRNA expression of autistic candidate genes (Ube3a, Gabrb3, Mecp2) and inflammatory cytokine genes (IL-1β, IL-6, TNF-α) were measured by RT-qPCR. Adult male offspring of ethanol-fed WT dams showed low birth weight compared to offspring of pair-fed WT dams. However, their body weights at adulthood were greater compared to the body weights of offspring of pair-fed WT dams. There were no body weight differences in offspring of TLR4-/- dams. Social interaction deficit was observed only in male offspring of ethanol-fed WT dams, but it was not observed in both male and female offspring of ethanol-fed TLR4-/- dams. Expressions of autism candidate genes, Gabrb3 and Ube3a, were elevated, while that of the Mecp2 gene was suppressed in the frontal cortex of male, but not female, offspring of ethanol-fed WT mice. The expressions of inflammatory cytokine genes, IL-1β, IL-6, and TNF-α, were also significantly increased in the frontal cortex of male, but not female, offspring of ethanol-fed dams. The changes in the expression of autistic and cytokine genes were unaffected in the offspring of ethanol-fed TLR4-/- dams. These data also indicate that TLR4 mediates FAE-induced changes in social interactions and gene expression in brain, suggesting that ethanol-induced LPS absorption from the maternal gut may be involved in gene expression changes in the fetal brain. [ABSTRACT FROM AUTHOR]

After the first initiation, the Fuel Air Explosive (FAE) cloud formed through fuel explosion dispersal and it will generate tremendous damaging power after being detonated the second time. As the damaging power is closely related to the determination of reinitiation time, it is of great significance to study the growth principle of FAE cloud by means of analyzing FAE cloud images. Combining with background subtraction and region growing, an improved region growing image processing method was proposed, in which the seeds of region growing abstracted through background subtraction method and the growing criterion was modified. With this method, the integrate area of cloud can be obtained for extracting geometric parameters. Experiments were carried out on both cloudy and sunny days, and image overlap score was used to quantitatively evaluate the accuracy of images segmentation. The result indicated that this image processing method has advantages of high precision and robustness. In addition, the computation burden is reduced significantly compared with traditional region growing method. [ABSTRACT FROM AUTHOR]

Summary: Apple Valsa canker, caused by the fungus Valsa mali, is one of the most destructive diseases of apple trees in East Asia. Feruloyl esterases (ferulic acid esterases, FAEs), which belong to a subclass of carboxylic esterases, can cleave ester bonds that crosslink hydroxycinnamic acids and arabinoxylans or certain pectins in plant cell walls. However, a pathogenic role of FAE has not been demonstrated in plant‐pathogenic fungi. In this study, the FAE gene family, including one type A, one type B, three type C and two type D FAE genes, was identified in V. mali. Five of the seven FAE genes had highly elevated transcript levels in V. mali–apple tree bark interactions compared with mycelia grown in axenic culture. Signal peptides of the VmFAEs were confirmed using yeast signal sequence trap assays. To examine whether FAEs are required for the pathogenicity of V. mali, seven single‐ and six double‐gene deletion mutants were generated. Compared with the wild‐type, three of the seven FAE single‐deletion mutants showed significantly reduced pathogenicity and three of the six FAE double‐deletion mutants exhibited greater reductions in pathogenicity, suggesting the joint action of FAEs in the V. mali–apple tree interaction. Most of the FAE mutants that exhibited a significant reduction in pathogenicity had significantly lower FAE activity than the wild‐type fungus. These results indicate that secreted FAEs are required for the full pathogenicity of the phytopathogenic fungus V. mali. [ABSTRACT FROM AUTHOR]

The present paper explores the connections between the radical sexual behavior of the main female characters in the TV show Lost Girl and Octavia Butler’s novel Fledgling, Bo and Shori respectively. This analysis works from a queer-ecological feminist perspective that understands that science ction as a genre presents rich opportunities for the development of feminist-queer sexual identities in female characters that in turn construct anti-patriarchal queer family structures that can truly transform the world. Este artículo explora las conexiones entre el comportamiento sexual radical de los personajes femeninos principales del programa de televisión Lost Girl y la novela de Octavia Butler, Fledgling, Bo y Shori respectivamente. El presente análisis trabaja desde una perspectiva feminista queer-ecológica, la cual entiende que el género literario de ciencia cción presenta enormes oportunidades para el desarrollo de identidades queer feministas que construyen a su vez estructuras familiares queer antipa-triarcales que pueden verdaderamente transformar el mundo.

The thermal behaviors and mechanism of nano-based fuel air explosive (FAE) were investigated by using DSC measurements in different situations and DSC/TG-FTIR-MS coupled technique. The thermal decomposition process of FAE under non-oxidizing environment was analyzed and described. The decomposition of FAE takes place in a multistage complex process. The first process is assigned to volatilization process of the volatile components. With an increase in temperature, isopropyl nitrate starts to break up into alkene and secondary alcohol. In the temperature range of 350-500 °C, the dominant volatile products are hydrocarbon fragments, CO and HO. At the same time, the full formulation of FAE and formulation without nano-Al powder were studied and compared. The thermal decomposition of other components in FAE is significantly promoted by nano-Al powder. [ABSTRACT FROM AUTHOR]

The article reports on a study regarding distribution of Estrogen Receptor (ER) in the thymus and bursa of fabricius (BF) in chick embryos. It discusses methodology of the study which includes preparation of tissue, their immunohistochemical analysis and analysis of ER mRNA by reverse transcriptase polymerase chain reaction technique. The study confirmed presence of ER in the thymus and BF which influence differentiation of thymic and bursal lymphocytes during embryogenesis.

The purpose of this study was to investigate the light and electron microscopic structure of Furstenberg's rosette region and to determine of uptake of macromolecules from follicle associated epithelium (FAE) of healthy cows in lactation period. In this study, 26 distal teat end taken from 10 animals in lactation period were used as material. Tissue samples were prepared for examination by light and transmission electron microscope. Indirect immunoperoxidase method was implemented to determine of cells containing IgA and IgG. Ferritin solution (25 mg/ml) was applied to distal teat end 1 h before slaughtered to show uptake of macromolecules in FAE. It was observed that Furstenberg's rosette region consists of lymphoid and nonlymphoid areas. Solitary and aggregate lymphoid follicles were seen in lymphoid areas. It was attracted attention that upper surfaces of these follicles were covered with FAE. IgA positive cells were seen in centrum germinativum of lymphoid follicles in the lymphoid region and subepithelial areas. High endothelial venules (HEV), which is characteristic feature of lympho-epithelial tissues, were observed at connective tissue which is around of the lymphoid follicles. In thin sections, the teat end tissue have been previously applied to ferritin, ferritin particles were detected in apical invaginations and pinocytotic vesicles of membranous cells (M cells). It was determined that there is Furstenbeg's rosette associated lymphoid tissue (FALT) in teat end and this region was generated spesific immune response against antigens after their uptaking and proccessing. Thus, we have reached conclusion that FALT may play a role mucosal immunity of teat end. [ABSTRACT FROM AUTHOR]

This study was aimed at the investigation of the structure of conjunctiva-associated lymphoid tissue (CALT) in the ostrich(Struthio camelus). The upper and lower eyelids of 5 healthy adult ostriches obtained from a slaughterhouse constituted thematerial of the study. Aggregated lymphoid follicles occupied a large area beneath the fibrous flap in the lower palpebralconjunctiva, while their distribution in the upper palpebral conjunctiva was observed to be limited to regions near thenasolacrimal punctum. Light microscopic examination revealed the conjunctival epithelium to differ between non-lymphoidand lymphoid regions. Non-lymphoid regions had pseudostratified prismatic epithelium containing goblet cells. Follicle-associated epithelium (FAE) in lymphoid regions was composed of single-layered squamous epithelium without goblet cells.Aggregated and/or solitary lymphoid follicles were present in the subepithelium. Dome area, germinal centre, corona and interfollicular region were able to be distinguished in lymphoid follicles. Furthermore, interfollicular regions contained high endothelial venules, which are involved in lymphocyte migration. Electron microscopic examination demonstrated that FAE was closely associated with immune system cells. Cells, which resembled typical M cells in having short, thick apical micro-folds and vesicles, were present in the FAE. In the present study, the structure of CALT was demonstrated in the ostrich (Struthio camelus), based on macroscopic, microscopic and ultrastructural findings. [ABSTRACT FROM AUTHOR]

Abstract: M cells are located in the follicle associated epithelium (FAE) of Peyer''s patches (PPs) in the small intestine, where they mediate the uptake and transcytosis of luminal antigens to the underlying lymphoid tissue. Toll-like receptors (TLRs) have emerged as key mediators in the innate immune response by recognising pathogen associated molecular patterns (PAMPs) expressed by microorganisms. TLRs have previously been shown to be differentially expressed in the gastrointestinal tract. In this study PP were harvested from BALB/c mice. Ulex europaeus agglutinin 1 (UAE-1) positive M cells were isolated from FAE and the expression of TLR1–9 transcripts in M cells, FAE and villus epithelium (VE) was compared by quantitative real-time PCR. Transcripts for TLR1, TLR2 and TLR4 were found to be expressed at a high level in M cells in comparison to VE, with no transcripts being detected in the FAE. TLR3 and TLR6 were not found to be expressed in M cells or in the FAE. TLR5 and TLR7 were found to be expressed at a higher level in FAE compared to M cells. TLR9, which recognises unmethylated CpG DNA of bacteria and viruses and TLR8, which recognises ssRNA, were found to be preferentially expressed in M cells compared to FAE and VE. [Copyright &y& Elsevier]

Abstract: The precise distribution and expression of Toll-like receptor (TLR) 9 in gut-associated lymphoid tissues (GALTs) has not been elucidated. In this study, we investigated the expression pattern of TLR9 in adult and neonatal swine GALTs by real-time quantitative PCR, western blot, confocal laser microscopy and flow cytometric analysis. The swine TLR9 gene was preferentially expressed in adult Peyer''s patches (Pps) and mesenteric lymph nodes (MLNs), which contained approximately three times higher TLR9 than the spleen. Other tissues exhibited only weak expression of TLR9. In neonatal swine, elevated expression of TLR9 was detected only in MLNs. We firstly showed that highly expressive (TLR9+) cells were formed in Pps and MLNs. In addition, TLR9+ cells were present not only in immune cells such as dendritic cells and B cells but also in follicle-associated epithelia (FAE) including membranous cells (M cells) in Pps. These results suggest that Pps and MLNs provide the host defense with the ability to respond to a variety of bioactive oligonucleotides (ODNs) from bacteria at a conductive site of initial immune responses. [Copyright &y& Elsevier]

Follicle-associated epithelium (FAE) covering Peyer's patches contains specialized epithelial M cells that take up ingested macromolecules and microorganisms from the lumen of the gut by transcytosis. Using high-density oligonucleotide microarrays, we analyzed the gene expression profiles of FAE and M cells in order to characterize their cellular phenotypes. The microarray data revealed that, among approximately 14,000 genes, 409 were expressed in FAE at twofold or higher levels compared to the intestinal epithelial cells (IECs) of the villi. These included genes involved in membrane traffic, host defense and transcriptional regulation, as well as uncharacterized genes. Real-time PCR and in situ hybridization analyses identified three molecules, ubiquitin D (Ub-D), tumor necrosis factor receptor superfamily 12a (TNFRsf12a), and transmembrane 4 superfamily 4 (Tm4sf4), which were predominantly distributed throughout FAE, but were expressed little, if at all, in IECs. By contrast, transcripts of secretory granule neuroendocrine protein 1 (Sgne-1) were scattered in FAE, and were co-localized with Ulex europaeus agglutinin-1 (UEA-1)-positive cells. This clearly suggests that expression of Sgne-1 in the gut is specific to M cells. Such a unique pattern of gene expression distinguishes FAE and M cells from IECs, and may reflect their cellular phenotype(s) associated with specific functional features. [ABSTRACT FROM PUBLISHER]

Fetal alcohol exposure (FAE) is associated with a variety of physiological and behavioral dysfunctions. Effects of FAE on reproduction have been described that include delayed puberty, altered gonadotrophin secretion and steroidogenesis, and altered sexual behavior. Earlier work suggested that pituitary function was compromised in aduR fetal alcohol-exposed female rats. This study examined the effects of LHRH and PMA in vitro on LHβ-mRNA expression in pituitary fragments from FAE animals; a separate experiment examined the effects of estradiol-17β on LHβ-mRNA under similar conditions. The results indicate that the pituitary glands of FAE females have a reduced ability to respond to these three stimuli. The reason for this reduced responsiveness to LHRH, PMA, and estradiol-17β is not clear, but the alterations suggest that LH synthesis is impeded following fetal ethanol exposure. [ABSTRACT FROM AUTHOR]

Objective: Children with fetal alcohol spectrum disorder (FASD) can easily be misdiagnosed as having ADHD., Method: A total of 164 children were compared on cognitive and behavioral measures for four groups of children: FASD, ADHD, FASD + ADHD, and other neuropsychological disorders., Results: The ADHD group was not significantly different from the "other diagnosis" group on any of the measurements. The children with FASD were found to perform significantly worse than ADHD on externalizing problems, Full-Scale IQ, and indices of Verbal Comprehension, Perceptual Reasoning, and Working Memory. The comorbid FASD + ADHD group was significantly weaker than ADHD on verbal comprehension measures. The FASD children demonstrated significantly higher levels of atypicality and aggression relative to ADHD, and the FASD + ADHD group demonstrated significantly higher levels of hyperactivity and withdrawal relative to ADHD., Conclusion: These results indicate that children with FASD display a differential behavioral and cognitive profile that is significantly poorer than children with ADHD and other types of neuropsychological disorders.

Human IgG4, normally the least abundant of the four subclasses of IgG in serum, displays a number of unique biological properties. It can undergo heavy-chain exchange, also known as Fab-arm exchange, leading to the formation of monovalent but bispecific antibodies, and it interacts poorly with FcγRII and FcγRIII, and complement. These properties render IgG4 relatively "non-inflammatory" and have made it a suitable format for therapeutic monoclonal antibody production. However, IgG4 is also known to undergo Fc-mediated aggregation and has been implicated in auto-immune disease pathology. We report here the high-resolution crystal structures, at 1.9 and 2.35 Å, respectively, of human recombinant and serum-derived IgG4-Fc. These structures reveal conformational variability at the CH3-CH3 interface that may promote Fab-arm exchange, and a unique conformation for the FG loop in the CH2 domain that would explain the poor FcγRII, FcγRIII and C1q binding properties of IgG4 compared with IgG1 and -3. In contrast to other IgG subclasses, this unique conformation folds the FG loop away from the CH2 domain, precluding any interaction with the lower hinge region, which may further facilitate Fab-arm exchange by destabilisation of the hinge. The crystals of IgG4-Fc also display Fc-Fc packing contacts with very extensive interaction surfaces, involving both a consensus binding site in IgG-Fc at the CH2-CH3 interface and known hydrophobic aggregation motifs. These Fc-Fc interactions are compatible with intact IgG4 molecules and may provide a model for the formation of aggregates of IgG4 that can cause disease pathology in the absence of antigen., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: Intestinal epithelial cells aid in mucosal defense by providing a physical barrier against entry of pathogenic bacteria and secreting antimicrobial peptides (AMPs). Autophagy is an important component of immune homeostasis. However, little is known about its role in specific cell types during bacterial infection in vivo. We investigated the role of autophagy in the response of intestinal epithelial and antigen-presenting cells to Salmonella infection in mice., Methods: We generated mice deficient in Atg16l1 in epithelial cells (Atg16l1(f/f) × Villin-cre) or CD11c(+) cells (Atg16l1(f/f) × CD11c-cre); these mice were used to assess cell type-specific antibacterial autophagy. All responses were compared with Atg16l1(f/f) mice (controls). Mice were infected with Salmonella enterica serovar typhimurium; cecum and small-intestine tissues were collected for immunofluorescence, histology, and quantitative reverse-transcription polymerase chain reaction analyses of cytokines and AMPs. Modulators of autophagy were screened to evaluate their effects on antibacterial responses in human epithelial cells., Results: Autophagy was induced in small intestine and cecum after infection with S typhimurium, and required Atg16l1. S typhimurium colocalized with microtubule-associated protein 1 light chain 3β (Map1lc3b or LC3) in the intestinal epithelium of control mice but not in Atg16l1(f/f) × Villin-cre mice. Atg16l1(f/f) × Villin-cre mice also had fewer Paneth cells and abnormal granule morphology, leading to reduced expression of AMPs. Consistent with these defective immune responses, Atg16l1(f/f) × Villin-cre mice had increased inflammation and systemic translocation of bacteria compared with control mice. In contrast, we observed few differences between Atg16l1(f/f) × CD11c-cre and control mice. Trifluoperazine promoted autophagy and bacterial clearance in HeLa cells; these effects were reduced upon knockdown of ATG16L1., Conclusions: Atg16l1 regulates autophagy in intestinal epithelial cells and is required for bacterial clearance. It also is required to prevent systemic infection of mice with enteric bacteria., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Oral mucosal immunization is a feasible and economic vaccination strategy. In order to achieve a successful oral mucosal vaccination, antigen delivery to gut immune inductive site and avoidance of oral tolerance induction should be secured. One promising approach is exploring the specific molecules expressed on the apical surfaces of M cells that have potential for antigen uptake and immune stimulation. We previously identified complement 5a receptor (C5aR) expression on human M-like cells and mouse M cells and confirmed its non-redundant role as a target receptor for antigen delivery to M cells using a model antigen. Here, we applied the OmpH ligand, which is capable of targeting the ligand-conjugated antigen to M cells to induce specific mucosal and systemic immunities against the EDIII of dengue virus (DENV). Oral immunization with the EDIII-OmpH efficiently targeted the EDIII to M cells and induced EDIII-specific immune responses comparable to those induced by co-administration of EDIII with cholera toxin (CT). Also, the enhanced responses by OmpH were characterized as Th2-skewed responses. Moreover, oral immunization using EDIII-OmpH did not induce systemic tolerance against EDIII. Collectively, we suggest that OmpH-mediated targeting of antigens to M cells could be used for an efficient oral vaccination against DENV infection., (Copyright © 2013 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Lipid metabolism is of crucial importance for pathogens. Lipids serve as cellular building blocks, signalling molecules, energy stores, posttranslational modifiers, and pathogenesis factors. Parasites rely on a complex system of uptake and synthesis mechanisms to satisfy their lipid needs. The parameters of this system change dramatically as the parasite transits through the various stages of its life cycle. Here we discuss the tremendous recent advances that have been made in the understanding of the synthesis and uptake pathways for fatty acids and phospholipids in apicomplexan and kinetoplastid parasites, including Plasmodium, Toxoplasma, Cryptosporidium, Trypanosoma and Leishmania. Lipid synthesis differs in significant ways between parasites from both phyla and the human host. Parasites have acquired novel pathways through endosymbiosis, as in the case of the apicoplast, have dramatically reshaped substrate and product profiles, and have evolved specialized lipids to interact with or manipulate the host. These differences potentially provide opportunities for drug development. We outline the lipid pathways for key species in detail as they progress through the developmental cycle and highlight those that are of particular importance to the biology of the pathogens and/or are the most promising targets for parasite-specific treatment., (Copyright © 2013 Elsevier Ltd. All rights reserved.)