Evolution, diversity, and function of the disease susceptibility gene Snn1 in wheat.

Septoria nodorum blotch (SNB), caused by Parastagonospora nodorum, is a disease of durum and common wheat initiated by the recognition of pathogen-produced necrotrophic effectors (NEs) by specific wheat genes. The wheat gene Snn1 was previously cloned, and it encodes a wall-associated kinase that directly interacts with the NE SnTox1 leading to programmed cell death and ultimately the development of SNB. Here, sequence analysis of Snn1 from 114 accessions including diploid, tetraploid, and hexaploid wheat species revealed that some wheat lines possess two copies of Snn1 (designated Snn1-B1 and Snn1-B2) approximately 120 kb apart. Snn1-B2 evolved relatively recently as a paralog of Snn1-B1, and both genes have undergone diversifying selection. Three point mutations associated with the formation of the first SnTox1-sensitive Snn1-B1 allele from a primitive wild wheat were identified. Four subsequent and independent SNPs, three in Snn1-B1 and one in Snn1-B2, converted the sensitive alleles to insensitive forms. Protein modeling indicated these four mutations could abolish Snn1-SnTox1 compatibility either through destabilization of the Snn1 protein or direct disruption of the protein-protein interaction. A high-throughput marker was developed for the absent allele of Snn1, and it was 100% accurate at predicting SnTox1-insensitive lines in both durum and spring wheat. Results of this study increase our understanding of the evolution, diversity, and function of Snn1-B1 and Snn1-B2 genes and will be useful for marker-assisted elimination of these genes for better host resistance.

Physicomechanical, morphological and tribo-deformation characteristics of lightweight WC/AZ31B Mg-matrix biocomposites for hip joint applications.

Exploring high strength materials with a higher concentration of reinforcements in the alloy proves to be a challenging task. This research has explored magnesium-based composites (AZ31B alloy) with tungsten carbide reinforcements, enhancing strength for medical joint replacements via league championship optimisation. The primary objective is to enhance medical joint replacement biomaterials employing magnesium-based composites, emphasising the AZ31B alloy with tungsten carbide reinforcements. The stir casting method is utilised in the manufacture of magnesium matrix composites (MMCs), including varied percentages of tungsten carbide (WC). The mechanical characteristics, such as micro-hardness, tensile strength, and yield strength, have been assessed and compared with computational simulations. The wear studies have been carried out to analyse the tribological behaviour of the composites. Additionally, this study investigates the prediction of stress and the distribution of forces inside bone and joint structures, therefore offering significant contributions to the field of biomedical research. This research contemplates the use of magnesium-based MMCs for the discovery of biomaterials suitable for medical joint replacement. The study focuses on the magnesium alloy AZ31B, with particles ranging in size from 40 to 60 microns used as the matrix material. Moreover, the outcomes have revealed that when combined with MMCs based on AZ31B-magnesium matrix, the WC particle emerges as highly effective reinforcements for the fabrication of lightweight, high-strength biomedical composites. This study uses the league championship optimisation (LCO) approach to identify critical variables impacting the synthesis of Mg MMCs from an AZ31B-based magnesium alloy. The scanning electron microscopy (SEM) images are meticulously analysed to depict the dispersion of WC particulates and the interface among the magnesium (Mg) matrix and WC reinforcement. The SEM analysis has explored the mechanisms underlying particle pull-out, the characteristics of inter-particle zones, and the influence of the AZ31B matrix on the enhancement of the mechanical characteristics of the composites. The application of finite element analysis (FEA) is being used in order to make predictions regarding the distribution of stress and the interactions of forces within the model of the hip joint. This study has compared the physico-mechanical and tribological characteristics of WC to distinct combinations of 0%, 5%, 10% and 15%, and its impact on the performance improvements. SEM analysis has confirmed the findings' improved strength and hardness, particularly when 10%-15% of WC was incorporated. Following the incorporation of 10% of WC particles within Mg-alloy matrix, the outcomes of the study has exhibited enhanced strength and hardness, which furthermore has been evident by utilising SEM analysis. Using ANSYS, structural deformation and stress levels are predicted, along with strength characteristics such as additional hardness of 71 HRC, tensile strength of 140-150 MPa, and yield strength closer to 100-110 MPa. The simulations yield significant insights into the behaviour of the joint under various loading conditions, thus enhancing the study's significance in biomedical environments.

IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFß.

Fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF) and systemic scleroderma (SSc), are commonly associated with high morbidity and mortality, thereby representing a significant unmet medical need. Interleukin 11 (IL11)-mediated cell activation has been identified as a central mechanism for promoting fibrosis downstream of TGFß. IL11 signaling has recently been reported to promote fibroblast-to-myofibroblast transition, thus leading to various pro-fibrotic phenotypic changes. We confirmed increased mRNA expression of IL11 and IL11Rα in fibrotic diseases by OMICs approaches and in situ hybridization. However, the vital role of IL11 as a driver for fibrosis was not recapitulated. While induction of IL11 secretion was observed downstream of TGFß signaling in human lung fibroblasts and epithelial cells, the cellular responses induced by IL11 was quantitatively and qualitatively inferior to that of TGFß at the transcriptional and translational levels. IL11 blocking antibodies inhibited IL11Rα-proximal STAT3 activation but failed to block TGFß-induced profibrotic signals. In summary, our results challenge the concept of IL11 blockade as a strategy for providing transformative treatment for fibrosis.

CD4+ T Cell Responses to Toxoplasma gondii Are a Double-Edged Sword.

CD4+ T cells have been found to play critical roles in the control of both acute and chronic Toxoplasma infection. Previous studies identified a protective role for the Toxoplasma CD4+ T cell-eliciting peptide AS15 (AVEIHRPVPGTAPPS) in C57BL/6J mice. Herein, we found that immunizing mice with AS15 combined with GLA-SE, a TLR-4 agonist in emulsion adjuvant, can be either helpful in protecting male and female mice at early stages against Type I and Type II Toxoplasma parasites or harmful (lethal with intestinal, hepatic, and spleen pathology associated with a storm of IL6). Introducing the universal CD4+ T cell epitope PADRE abrogates the harmful phenotype of AS15. Our findings demonstrate quantitative and qualitative features of an effective Toxoplasma-specific CD4+ T cell response that should be considered in testing next-generation vaccines against toxoplasmosis. Our results also are cautionary that individual vaccine constituents can cause severe harm depending on the company they keep.

Genome-wide association mapping of resistance to the foliar diseases septoria nodorum blotch and tan spot in a global winter wheat collection.

Septoria nodorum blotch (SNB) and tan spot, caused by the necrotrophic fungal pathogens Parastagonospora nodorum and Pyrenophora tritici-repentis, respectively, often occur together as a leaf spotting disease complex on wheat (Triticum aestivum L.). Both pathogens produce necrotrophic effectors (NEs) that contribute to the development of disease. Here, genome-wide association analysis of a diverse panel of 264 winter wheat lines revealed novel loci on chromosomes 5A and 5B associated with sensitivity to the NEs SnTox3 and SnTox5 in addition to the known sensitivity genes for NEs Ptr/SnToxA, SnTox1, SnTox3, and SnTox5. Sensitivity loci for SnTox267 and Ptr ToxB were not detected. Evaluation of the panel with five P. nodorum isolates for SNB development indicated the Snn3-SnTox3 and Tsn1-SnToxA interactions played significant roles in disease development along with additional QTL on chromosomes 2A and 2D, which may correspond to the Snn7-SnTox267 interaction. For tan spot, the Tsc1-Ptr ToxC interaction was associated with disease caused by two isolates, and a novel QTL on chromosome 7D was associated with a third isolate. The Tsn1-ToxA interaction was associated with SNB but not tan spot. Therefore some, but not all, of the previously characterized host gene-NE interactions in these pathosystems play significant roles in disease development in winter wheat. Based on these results, breeders should prioritize the selection of resistance alleles at the Tsc1, Tsn1, Snn3, and Snn7 loci as well as the 2A and 7D QTL to obtain good levels of resistance to SNB and tan spot in winter wheat. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01400-5.

Association Mapping of Resistance to Tan Spot in the Global Durum Panel.

Tan spot, caused by the necrotrophic fungal pathogen Pyrenophora tritici-repentis (Ptr), is an important disease of durum and common wheat worldwide. Compared with common wheat, less is known about the genetics and molecular basis of tan spot resistance in durum wheat. We evaluated 510 durum lines from the Global Durum Wheat Panel (GDP) for sensitivity to the necrotrophic effectors (NEs) Ptr ToxA and Ptr ToxB and for reaction to Ptr isolates representing races 1 to 5. Overall, susceptible durum lines were most prevalent in South Asia, the Middle East, and North Africa. Genome-wide association analysis showed that the resistance locus Tsr7 was significantly associated with tan spot caused by races 2 and 3, but not races 1, 4, or 5. The NE sensitivity genes Tsc1 and Tsc2 were associated with susceptibility to Ptr ToxC- and Ptr ToxB-producing isolates, respectively, but Tsn1 was not associated with tan spot caused by Ptr ToxA-producing isolates, which further validates that the Tsn1-Ptr ToxA interaction does not play a significant role in tan spot development in durum. A unique locus on chromosome arm 2AS was associated with tan spot caused by race 4, a race once considered avirulent. A novel trait characterized by expanding chlorosis leading to increased disease severity caused by the Ptr ToxB-producing race 5 isolate DW5 was identified, and this trait was governed by a locus on chromosome 5B. We recommend that durum breeders select resistance alleles at the Tsr7, Tsc1, Tsc2, and the chromosome 2AS loci to obtain broad resistance to tan spot.

Evaluation of Wheat Cultivars and Germplasm Lines for Resistance to Pratylenchus neglectus Populations Collected in North Dakota.

Root-lesion nematode (RLN; Pratylenchus neglectus) is a migratory endoparasite and a major soilborne pathogen that affects wheat (Triticum spp.) production worldwide. Genetic resistance is one of the most economical and effective ways to manage P. neglectus in wheat. This study evaluated 37 local cultivars and germplasm lines in seven greenhouse experiments, including 26 hexaploid wheat, six durum wheat, two synthetic hexaploid wheat, one emmer wheat, and two triticale for P. neglectus resistance from 2016 to 2020. North Dakota field soils infested with two RLN populations (350 to 1,125 nematodes per kilogram of soil) were used for resistance screening under controlled greenhouse conditions. The final nematode population density for each cultivar and line was counted under the microscope to categorize the resistance ranking of these entries as resistant, moderately resistant, moderately susceptible, and susceptible. Out of the 37 cultivars and lines, one was classified as resistant (Brennan); 18 were moderately resistant (Divide, Carpio, Prosper, Advance, Alkabo, SY Soren, Barlow, Bolles, Select, Faller, Briggs, WB Mayville, SY Ingmar, W7984, PI 626573, Ben, Grandin, and Villax St. Jose); 11 were moderately susceptible; and seven were susceptible to P. neglectus. The resistant to moderately resistant lines identified in this study could be used in breeding programs after the resistance genes or loci are further elucidated. This research provides valuable information about P. neglectus resistance among wheat and triticale cultivars used in the Upper Midwest region of the United States.

Dental professionals' attitude and willingness to respond during disaster events: a cross-sectional study.

INTRODUCTION: In the present times, natural and man-made threats have questioned our existence on this planet. Health care professionals need to be aware of all the procedures to follow during such an event that threatens to paralyze the entire community and should be able to respond effectively. OBJECTIVE: The present study was conducted to assess the willingness and attitude of dental professionals to render help during any disaster or catastrophic event. MATERIAL AND METHODS: The present cross-sectional study among 480 subjects who were residing in Tricity (Chandigarh, Mohali and Panchkula). Informed consent was taken from all the subjects. Systematic random sampling methodology was employed for selection for study sample. The study utilized a self-designed close-ended questionnaire written in English and verified by experts. The questionnaire was divided into two parts to collect the required information. The data was analyzed using SPSS software version 21; chi-square test and multiple regression analysis were used to arrive at the results. RESULTS: More than 85% of subjects had awareness regarding natural and manmade disasters. A positive response was given by 79.2% of subjects regarding willingness to help during disaster. Educational qualification of subjects was significantly associated with attitude towards some aspects of disaster response (p<0.05). Postgraduate subjects and subjects who were academicians were more willing to render help (OR: 2.18 & 3.65 respectively). CONCLUSIONS: The study emphasizes the need for educational and training programs for dentists' regarding disaster management. A short course on emergency and disaster management can be included in undergraduate and postgraduate dental curriculum.

Tissues and organ printing: An evolution of technology and materials.

Since its beginnings, three-dimensional printing (3DP) technology has been successful because of ongoing advances in operating principles, the range of materials and cost-saving measures. However, the 3DP technological progressions in the biomedical sector have majorly taken place in the last decade after the evolution of novel 3DP systems, generally categorised as bioprinters and biomaterials to provide a replacement, transplantation or regeneration of the damaged organs and tissue constructs of the human body. There is now substantial scientific literature accessible to support the benefits of digital healthcare procedures with the help of bioprinters. It is of the highest significance to know the fundamental principles of the available printers and the compatibility of biomaterials as their feedstock, notwithstanding the huge potential of bioprinting systems to manufacture organs and other human body components. This paper provides a precise and helpful reading of the different categories of bioprinters, suitable biomaterials, numerical simulations and modelling and examples of much acknowledged clinical practices. The paper will also cite the prominent issues that still have not received desired solutions. Overall, the article will be of great use for all the professionals, scholars and engineers concerned with the 3DP, bioprinting and biomaterials.

Optimization of WEDM Parameters While Machining Biomedical Materials Using EDAS-PSO.

In the present work, an attempt has been made to study the influence of process parameters of the wire electric discharge machining (WEDM) process on the machining characteristics. The commercially pure titanium is machined by WEDM using brass wire as an electrode. The input parameters in this work were pulse on-time (Aon), pulse off-time (Aoff), servo voltage (SV) and wire tension (WT). On the other hand, dimensional accuracy (DA), average surface roughness (Ra) and maximum surface roughness (Rz) were chosen as the response parameters. The empirical relations developed for response characteristics were solved collectively using Evaluation Based on Distance from Average Solution (EDAS) and Particle Swarm Optimization (PSO). The optimized setting for minimizing the surface irregularities while machining titanium alloy on WEDM is predicted as Aon: 8 µs; Aoff: 13 µs; SV: 45 V; and WT: 8 N. Moreover, the predicted solution at the optimized parametric settings came out as DA: 95%; Ra: 3.163 µm; Rz: 22.99 µm; WL: 0.0182 g; and DR: 0.1277 mm. The validation experiments at the optimized setting showed the close agreement between predicted and experimental values. The morphological study by scanning electron microscopy (SEM) at the optimized setting revealed a significant reduction in surface defects such as micro cracks, micro cavities, globules and sub-surfaces, etc. In a nutshell, the study justified the effectiveness of EDAS-PSO in efficiently predicting the results for machining of pure titanium (Grade 2) using the WEDM process.

The Tight Junction Protein ZO-1 Is Dispensable for Barrier Function but Critical for Effective Mucosal Repair.

BACKGROUNDS & AIMS: Increased permeability is implicated in the pathogenesis of intestinal disease. In vitro and in vivo studies have linked down-regulation of the scaffolding protein ZO-1, encoded by the TJP1 gene, to increased tight junction permeability. This has not, however, been tested in vivo. Here, we assessed the contributions of ZO-1 to in vivo epithelial barrier function and mucosal homeostasis. METHODS: Public Gene Expression Omnibus data sets and biopsy specimens from patients with inflammatory bowel disease (IBD) and healthy control individuals were analyzed. Tjp1f/f;vil-CreTg mice with intestinal epithelial-specific ZO-1 knockout (ZO-1KO.IEC) mice and Tjp1f/f mice littermates without Cre expression were studied using chemical and immune-mediated models of disease as well as colonic stem cell cultures. RESULTS: ZO-1 transcript and protein expression were reduced in biopsy specimens from patients with IBD. Despite mildly increased intestinal permeability, ZO-1KO.IEC mice were healthy and did not develop spontaneous disease. ZO-1KO.IEC mice were, however, hypersensitive to mucosal insults and displayed defective repair. Furthermore, ZO-1-deficient colonic epithelia failed to up-regulate proliferation in response to damage in vivo or Wnt signaling in vitro. ZO-1 was associated with centrioles in interphase cells and mitotic spindle poles during division. In the absence of ZO-1, mitotic spindles failed to correctly orient, resulting in mitotic catastrophe and abortive proliferation. ZO-1 is, therefore, critical for up-regulation of epithelial proliferation and successful completion of mitosis. CONCLUSIONS: ZO-1 makes critical, tight junction-independent contributions to Wnt signaling and mitotic spindle orientation. As a result, ZO-1 is essential for mucosal repair. We speculate that ZO-1 down-regulation may be one cause of ineffective mucosal healing in patients with IBD.

Effect of Different Lubricating Environment on the Tribological Performance of CNT Filled Glass Reinforced Polymer Composite.

In recent years, the engineering implications of carbon nanotubes (CNTs) have progressed enormously due to their versatile characteristics. In particular, the role of CNTs in improving the tribological performances of various engineering materials is well documented in the literature. In this work, an investigation has been conducted to study the tribological behaviour of CNTs filled with glass-reinforced polymer (GFRP) composites in dry sliding, oil-lubricated, and gaseous (argon) environments in comparison to unfilled GFRP composites. The tribological study has been conducted on hardened steel surfaces at different loading conditions. Further, the worn surfaces have been examined for a particular rate of wear. Field-emission scanning electron (FESEM) microscopy was used to observe wear behaviours. The results of this study explicitly demonstrate that adding CNTs to GFRP composites increases wear resistance while lowering friction coefficient in all sliding environments. This has also been due to the beneficial strengthening and self-lubrication properties caused by CNTs on GFRP composites, according to FESEM research.

Surface Characteristics of Machined Polystyrene with 3D Printed Thermoplastic Tool.

An effort is made in this work to appraise the surface characteristics of machined expandable polystyrene (EPS) with a novel 3D printed thermoplastic acrylonitrile-butadiene-styrene (ABS) tool. Linear grooves on EPS were made on a vertical milling machine that was modified to conduct experiments in the laboratory. The tests were designed as per the Taguchi L9 based factorial design of experimentation while varying process parameters such as depth of cut, spindle speed, and feed rate. The machining responses dimensional accuracy and surface roughness of the machined grooves were studied. Furthermore, the surface topography of the machined specimens was considered to investigate the mechanism of material removal in response to the processing conditions. Moreover, mathematical models developed for the prediction of the output responses showed a significant correlation with the experimental results. The results of the statistical study indicate that the surface roughness is influenced by the spindle speed and dimensional accuracy by the depth-of-cut. Overall, the findings of the experimental work advocated the feasibility of 3D printed thermoplastic tools for machining soft polymeric materials. It can become a useful alternative for mass and batch production.

Inactivation of paracellular cation-selective claudin-2 channels attenuates immune-mediated experimental colitis in mice.

The tight junction protein claudin-2 is upregulated in disease. Although many studies have linked intestinal barrier loss to local and systemic disease, these have relied on macromolecular probes. In vitro analyses show, however, that these probes cannot be accommodated by size- and charge-selective claudin-2 channels. We sought to define the impact of claudin-2 channels on disease. Transgenic claudin-2 overexpression or IL-13-induced claudin-2 upregulation increased intestinal small cation permeability in vivo. IL-13 did not, however, affect permeability in claudin-2-knockout mice. Claudin-2 is therefore necessary and sufficient to effect size- and charge-selective permeability increases in vivo. In chronic disease, T cell transfer colitis severity was augmented or diminished in claudin-2-transgenic or -knockout mice, respectively. We translated the in vitro observation that casein kinase-2 (CK2) inhibition blocks claudin-2 channel function to prevent acute, IL-13-induced, claudin-2-mediated permeability increases in vivo. In chronic immune-mediated colitis, CK2 inhibition attenuated progression in claudin-2-sufficient, but not claudin-2-knockout, mice, i.e., the effect was claudin-2 dependent. Paracellular flux mediated by claudin-2 channels can therefore promote immune-mediated colitis progression. Although the mechanisms by which claudin-2 channels intensify disease remain to be defined, these data suggest that claudin-2 may be an accessible target in immune-mediated disorders, including inflammatory bowel disease.

3D printed biodegradable functional temperature-stimuli shape memory polymer for customized scaffoldings.

Shape memory polymers (SMPs) and their composites have become the prominent choice of the various industries owing to the unique inherent characteristics which can be stimulated through the exposure of external stimuli. The use of SMPs in the three-dimensional (3D) technologies has produced enormous advantages. However, the potential of SMPs in 3D printing has limitedly explored. In the present study, an investigation was performed to study the shape memory effect (SME) of the fused filament fabricated (FFF) chitosan (CS) reinforced poly-lactic-acid (PLA) based porous scaffolds. Firstly, the composite filaments, with 1, 1.5, and 2% wt. of CS, were fabricated by using the twin-screw extrusion process, which was later used to print the test specimens at different infill density. The printed samples were selectively pre-elongated to 2.5 mm and then processed through direct heating, at 60-70 °C, for enabling the SME. It has been observed that the CS particles acted as rigid phases and interrupted the re-ordering of PLA chain. However, the scaffoldings showed 18.8% shape recovery at optimized process parametric settings. In addition, wettability and biocompatibility analyses of developed scaffoldings have also been performed to investigate the biological aspects of the developed scaffoldings. The stimulated samples found to be possessed with good wettability and cell proliferation. Overall, the 3D printed PLA/CS porous scaffoldings have shown significant shape recovery characteristics and are biologically active to be used as self-healing implants for acute bone deficiencies.

Intracellular MLCK1 diversion reverses barrier loss to restore mucosal homeostasis.

Epithelial barrier loss is a driver of intestinal and systemic diseases. Myosin light chain kinase (MLCK) is a key effector of barrier dysfunction and a potential therapeutic target, but enzymatic inhibition has unacceptable toxicity. Here, we show that a unique domain within the MLCK splice variant MLCK1 directs perijunctional actomyosin ring (PAMR) recruitment. Using the domain structure and multiple screens, we identify a domain-binding small molecule (divertin) that blocks MLCK1 recruitment without inhibiting enzymatic function. Divertin blocks acute, tumor necrosis factor (TNF)-induced MLCK1 recruitment as well as downstream myosin light chain (MLC) phosphorylation, barrier loss, and diarrhea in vitro and in vivo. Divertin corrects barrier dysfunction and prevents disease development and progression in experimental inflammatory bowel disease. Beyond applications of divertin in gastrointestinal disease, this general approach to enzymatic inhibition by preventing access to specific subcellular sites provides a new paradigm for safely and precisely targeting individual properties of enzymes with multiple functions.

Graft-versus-host disease propagation depends on increased intestinal epithelial tight junction permeability.

Graft-versus-host disease (GVHD) is a complication of hematopoietic stem cell transplantation (HSCT) that affects multiple organs. GVHD-associated intestinal damage can be separated into two distinct phases, initiation and propagation, which correspond to conditioning-induced damage and effector T cell activation and infiltration, respectively. Substantial evidence indicates that intestinal damage induced by pretransplant conditioning is a key driver of GVHD initiation. Here, we aimed to determine the impact of dysregulated intestinal permeability on the subsequent GVHD propagation phase. The initiation phase of GVHD was unchanged in mice lacking long MLCK (MLCK210), an established regulator of epithelial tight junction permeability. However, MLCK210-deficient mice were protected from sustained barrier loss and exhibited limited GVHD propagation, as indicated by reduced histopathology, fewer CD8+ effector T cells in the gut, and improved overall survival. Consistent with these findings, intestinal epithelial MLCK210 expression and enzymatic activity were similarly increased in human and mouse GVHD biopsies. Intestinal epithelial barrier loss mediated by MLCK210 is therefore a key driver of the GVHD propagation. These data suggest that inhibition of MLCK210-dependent barrier regulation may be an effective approach to limiting GVHD progression.

The scaffolding protein ZO-1 coordinates actomyosin and epithelial apical specializations in vitro and in vivo.

Polarized epithelia assemble into sheets that compartmentalize organs and generate tissue barriers by integrating apical surfaces into a single, unified structure. This tissue organization is shared across organs, species, and developmental stages. The processes that regulate development and maintenance of apical epithelial surfaces are, however, undefined. Here, using an intestinal epithelial-specific knockout (KO) mouse and cultured epithelial cells, we show that the tight junction scaffolding protein zonula occludens-1 (ZO-1) is essential for development of unified apical surfaces in vivo and in vitro We found that U5 and GuK domains of ZO-1 are necessary for proper apical surface assembly, including organization of microvilli and cortical F-actin; however, direct interactions with F-actin through the ZO-1 actin-binding region (ABR) are not required. ZO-1 lacking the PDZ1 domain, which binds claudins, rescued apical structure in ZO-1-deficient epithelia, but not in cells lacking both ZO-1 and ZO-2, suggesting that heterodimerization with ZO-2 restores PDZ1-dependent ZO-1 interactions that are vital to apical surface organization. Pharmacologic F-actin disruption, myosin II motor inhibition, or dynamin inactivation restored apical epithelial structure in vitro and in vivo, indicating that ZO-1 directs epithelial organization by regulating actomyosin contraction and membrane traffic. We conclude that multiple ZO-1-mediated interactions contribute to coordination of epithelial actomyosin function and genesis of unified apical surfaces.

Hepatitis C: Knowledge and awareness of private dental practitioners of a tricity in India.

BACKGROUND: Dental health-care personnel are at an increased risk toward infections caused by various microorganisms including hepatitis B and hepatitis C viruses (HCV). A dentist can play an important role in the prevention of HCV by considering every patient as a potential carrier for hepatitis. Therefore, the present study was conducted to assess the knowledge and awareness of dental health-care professionals regarding various aspects of HCV. MATERIALS AND METHODS: A cross-sectional study was conducted among 247 private dental practitioners of tricity. A close-ended self-structured questionnaire was administered which contained 12 questions on knowledge and awareness regarding HCV infection keeping in view the time constraints. Categorization of knowledge scores was done at three levels - poor, moderate, and good. Statistical analysis was done using ANOVA and Student's t-test. RESULTS: Nearly 96% (102) of postgraduates and 84% (117) of graduates had heard about HCV. 45.5% (112) had poor knowledge scores, 33.6% (83) had moderate knowledge scores, and only 21% (52) of participants had good knowledge scores. On the opinion of treating an HCV-infected patient by a dentist, only 61% (65) of postgraduates and 46% (64) of graduates agreed. There was statistically significant association of mean knowledge scores with gender, education level, and experience (P < 0.05). CONCLUSION: Majority of the dental professionals lacked knowledge regarding HCV infection and were not fully aware regarding certain aspects. Therefore, there is an urgent need for modification of the existing dental curriculum so that knowledge regarding these diseases can be imparted during graduation.

The Microbiome Activates CD4 T-cell-mediated Immunity to Compensate for Increased Intestinal Permeability.

BACKGROUND & AIMS: Despite a prominent association, chronic intestinal barrier loss is insufficient to induce disease in human subjects or experimental animals. We hypothesized that compensatory mucosal immune activation might protect individuals with increased intestinal permeability from disease. We used a model in which intestinal barrier loss is triggered by intestinal epithelial-specific expression of constitutively active myosin light chain kinase (CA-MLCK). Here we asked whether constitutive tight junction barrier loss impacts susceptibility to enteric pathogens. METHODS: Acute or chronic Toxoplasma gondii or Salmonella typhimurium infection was assessed in CA-MLCK transgenic or wild-type mice. Germ-free mice or those lacking specific immune cell populations were used to investigate the effect of microbial-activated immunity on pathogen translocation in the context of increased intestinal permeability. RESULTS: Acute T gondii and S typhimurium translocation across the epithelial barrier was reduced in CA-MLCK mice. This protection was due to enhanced mucosal immune activation that required CD4+ T cells and interleukin 17A but not immunoglobulin A. The protective mucosal immune activation in CA-MLCK mice depended on segmented filamentous bacteria (SFB), because protection against early S typhimurium invasion was lost in germ-free CA-MLCK mice but could be restored by conventionalization with SFB-containing, not SFB-deficient, microbiota. In contrast, chronic S typhimurium infection was more severe in CA-MLCK mice, suggesting that despite activation of protective mucosal immunity, barrier defects ultimately result in enhanced disease progression. CONCLUSIONS: Increased epithelial tight junction permeability synergizes with commensal bacteria to promote intestinal CD4+ T-cell expansion and interleukin 17A production that limits enteric pathogen invasion.