An immunodominant NP105-113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease.

NP105-113-B*07:02-specific CD8+ T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP105-113-B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52). We demonstrated a beneficial association of NP105-113-B*07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP105-113-B*07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP105-113-B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design.

cBAF complex components and MYC cooperate early in CD8+ T cell fate.

The identification of mechanisms to promote memory T (Tmem) cells has important implications for vaccination and anti-cancer immunotherapy1-4. Using a CRISPR-based screen for negative regulators of Tmem cell generation in vivo5, here we identify multiple components of the mammalian canonical BRG1/BRM-associated factor (cBAF)6,7. Several components of the cBAF complex are essential for the differentiation of activated CD8+ T cells into T effector (Teff) cells, and their loss promotes Tmem cell formation in vivo. During the first division of activated CD8+ T cells, cBAF and MYC8 frequently co-assort asymmetrically to the two daughter cells. Daughter cells with high MYC and high cBAF display a cell fate trajectory towards Teff cells, whereas those with low MYC and low cBAF preferentially differentiate towards Tmem cells. The cBAF complex and MYC physically interact to establish the chromatin landscape in activated CD8+ T cells. Treatment of naive CD8+ T cells with a putative cBAF inhibitor during the first 48 h of activation, before the generation of chimeric antigen receptor T (CAR-T) cells, markedly improves efficacy in a mouse solid tumour model. Our results establish cBAF as a negative determinant of Tmem cell fate and suggest that manipulation of cBAF early in T cell differentiation can improve cancer immunotherapy.

Glyphosate: Impact on the microbiota-gut-brain axis and the immune-nervous system, and clinical cases of multiorgan toxicity.

Glyphosate (GLP) and GLP-based herbicides (GBHs), such as polyethoxylated tallow amine-based GLP surfactants (GLP-SH), developed in the late 70', have become the most popular and controversial agrochemicals ever produced. Nowadays, GBHs have reached 350 million hectares of crops in over 140 countries, with an annual turnover of 5 billion and 11 billion USD in the U.S.A. and worldwide, respectively. Because of the highly efficient inhibitory activity of GLP targeted to the 5-enolpyruvylshikimate-3-phosphate synthase pathway, present in plants and several bacterial strains, the GLP-resistant crop-based genetic agricultural revolution has decreased famine and improved the costs and quality of living in developing countries. However, this progress has come at the cost of the 50-year GBH overuse, leading to environmental pollution, animal intoxication, bacterial resistance, and sustained occupational exposure of the herbicide farm and companies' workers. According to preclinical and clinical studies covered in the present review, poisoning with GLP, GLP-SH, and GBHs devastatingly affects gut microbiota and the microbiota-gut-brain (MGB) axis, leading to dysbiosis and gastrointestinal (GI) ailments, as well as immunosuppression and inappropriate immunostimulation, cholinergic neurotransmission dysregulation, neuroendocrinal system disarray, and neurodevelopmental and neurobehavioral alterations. Herein, we mainly focus on the contribution of gut microbiota (GM) to neurological impairments, e.g., stroke and neurodegenerative and neuropsychiatric disorders. The current review provides a comprehensive introduction to GLP's microbiological and neurochemical activities, including deviation of the intestinal Firmicutes-to-Bacteroidetes ratio, acetylcholinesterase inhibition, excitotoxicity, and mind-altering processes. Besides, it summarizes and critically discusses recent preclinical studies and clinical case reports concerning the harmful impacts of GBHs on the GI tract, MGB axis, and nervous system. Finally, an insightful comparison of toxic effects caused by GLP, GBH-SH, and GBHs is presented. To this end, we propose a first-to-date survey of clinical case reports on intoxications with these herbicides.

Cardiac MRI Risk Stratification for Dilated Cardiomyopathy with Left Ventricular Ejection Fraction of 35% or Higher.

Background Studies over the past 15 years have demonstrated that a considerable number of patients with dilated cardiomyopathy (DCM) who died from sudden cardiac death (SCD) had a left ventricular (LV) ejection fraction (LVEF) of 35% or higher. Purpose To identify clinical and cardiac MRI risk factors for adverse events in patients with DCM and LVEF of 35% or higher. Materials and Methods In this retrospective study, consecutive patients with DCM and LVEF of 35% or higher who underwent cardiac MRI between January 2010 and December 2017 were included. The primary end point was a composite of SCD or aborted SCD. The secondary end point was a composite of all-cause mortality, heart transplant, or hospitalization for heart failure. The risk factors for the primary and secondary end points were identified with multivariable Cox analysis. Results A total of 466 patients with DCM and LVEF of 35% or higher (mean age, 44 years ± 14 [SD]; 358 men) were included. During a mean follow-up of 79 months ± 30 (SD) (range, 7-143 months), 40 patients reached the primary end point and 61 reached the secondary end point. In the adjusted analysis, age (hazard ratio [HR], 1.03 per year [95% CI: 1.00, 1.05]; P = .04), family history of SCD (HR, 3.4 [95% CI: 1.3, 8.8]; P = .01), New York Heart Association (NYHA) class III or IV (HR vs NYHA class I or II, 2.1 [95% CI: 1.1, 3.9]; P = .02), and myocardial scar at late gadolinium enhancement (LGE) MRI greater than or equal to 7.1% of the LV mass (HR, 4.4 [95% CI: 2.4, 8.3]; P < .001) were associated with SCD or aborted SCD. For the composite secondary end point, LGE greater than or equal to 7.1% of the LV mass (HR vs LGE <7.1%, 2.0 [95% CI: 1.2, 3.4]; P = .01), left atrial maximum volume index, and reduced global longitudinal strain were independent predictors. Conclusion For patients with dilated cardiomyopathy and left ventricular (LV) ejection fraction of 35% or higher, cardiac MRI-defined myocardial scar greater than or equal to 7.1% of the LV mass was associated with sudden cardiac death (SCD) or aborted SCD. © RSNA, 2022 Online supplemental material is available for this article.

Type I interferon protects antiviral CD8+ T cells from NK cell cytotoxicity.

Despite development of new antiviral drugs, viral infections are still a major health problem. The most potent antiviral defense mechanism is the innate production of type I interferon (IFN-I), which not only limits virus replication but also promotes antiviral T cell immunity through mechanisms, which remain insufficiently studied. Using the murine lymphocytic choriomeningitis virus model system, we show here that IFN-I signaling on T cells prevented their rapid elimination in vivo. Microarray analyses uncovered that IFN-I triggered the expression of selected inhibitory NK-cell-receptor ligands. Consequently, T cell immunity of IFN-I receptor (IFNAR)-deficient T cells could be restored by NK cell depletion or in NK-cell-deficient hosts (Nfil3(-/-)). The elimination of Ifnar1(-/-) T cells was dependent on NK-cell-mediated perforin expression. In summary, we identified IFN-I as a key player regulating the protection of T cells against regulatory NK cell function.

A novel cardiac magnetic resonance-based personalized risk stratification model in dilated cardiomyopathy: a prospective study.

OBJECTIVES: To explore individual weight of cardiac magnetic resonance (CMR) metrics to predict mid-term outcomes in patients with dilated cardiomyopathy (DCM), and develop a risk algorithm for mid-term outcome based on CMR biomarkers. MATERIALS AND METHODS: Patients with DCM who underwent CMR imaging were prospectively enrolled in this study. The primary endpoint was a composite of heart failure (HF) death, sudden cardiac death (SCD), aborted SCD, and heart transplantation. RESULTS: A total of 407 patients (age 48.1 ± 13.8 years, 331 men) were included in the final analysis. During a median follow-up of 21.7 months, 63 patients reached the primary endpoint. NYHA class III/IV (HR = 2.347 [1.073-5.133], p = 0.033), left ventricular ejection fraction (HR = 0.940 [0.909-0.973], p < 0.001), late gadolinium enhancement (LGE) > 0.9% and ≤ 6.6% (HR = 3.559 [1.020-12.412], p = 0.046), LGE > 6.6% (HR = 6.028 [1.814-20.038], p = 0.003), and mean extracellular volume (ECV) fraction ≥ 32.8% (HR = 5.922 [2.566-13.665], p < 0.001) had a significant prognostic association with the primary endpoints (C-statistic: 0.853 [0.810-0.896]). Competing risk regression analyses showed that patients with mean ECV fraction ≥ 32.8%, LGE ≥ 5.9%, global circumferential strain ≥ - 5.6%, or global longitudinal strain ≥ - 7.3% had significantly shorter event-free survival due to HF death and heart transplantation. Patients with mean ECV fraction ≥ 32.8% and LGE ≥ 5.9% had significantly shorter event-free survival due to SCD or aborted SCD. CONCLUSION: ECV fraction may be the best independently risk factor for the mid-term outcomes in patients with DCM, surpassing LVEF and LGE. LGE has a better prognostic value than other CMR metrics for SCD and aborted SCD. The risk stratification model we developed may be a promising non-invasive tool for decision-making and prognosis. CLINICAL RELEVANCE STATEMENT: "One-stop" assessment of cardiac function and myocardial characterization using cardiac magnetic resonance might improve risk stratification of patients with DCM. In this prospective study, we propose a novel risk algorithm in DCM including NYHA functional class, LVEF, LGE, and ECV. KEY POINTS: • The present study explores individual weight of CMR metrics for predicting mid-term outcomes in dilated cardiomyopathy. • We have developed a novel risk algorithm for dilated cardiomyopathy that includes cardiac functional class, ejection fraction, late gadolinium enhancement, and extracellular volume fraction. • Personalized risk model derived by CMR contributes to clinical assessment and individual decision-making.

Enumerating Stable Nanopores in Graphene and Their Geometrical Properties Using the Combinatorics of Hexagonal Lattices.

Nanopores in two-dimensional (2D) materials, including graphene, can be used for a variety of applications, such as gas separations, water desalination, and DNA sequencing. So far, however, all plausible isomeric shapes of graphene nanopores have not been enumerated. Instead, a probabilistic approach has been followed to predict nanopore shapes in 2D materials, due to the exponential increase in the number of nanopores as the size of the vacancy increases. For example, there are 12 possible isomers when N = 6 atoms are removed, a number that theoretically increases to 11.7 million when N = 20 atoms are removed from the graphene lattice. In this regard, the development of a smaller, exhaustive data set of stable nanopore shapes can help future experimental and theoretical studies focused on using nanoporous 2D materials in various applications. In this work, we use the theory of 2D triangular "lattice animals" to create a library of all stable graphene nanopore shapes based on a modification of a well-known algorithm in the mathematical combinatorics of polyforms known as Redelmeier's algorithm. We show that there exists a correspondence between graphene nanopores and triangular polyforms (called polyiamonds) as well as hexagonal polyforms (called polyhexes). We develop the concept of a polyiamond ID to identify unique nanopore isomers. We also use concepts from polyiamond and polyhex geometries to eliminate unstable nanopores containing dangling atoms, bonds, and moieties. We verify using density functional theory calculations that such pores are indeed unstable. The exclusion of these unstable nanopores leads to a remarkable reduction in the possible nanopores from 11.7 million for N = 20 to only 0.184 million nanopores, thereby indicating that the number of stable nanopores is almost 2 orders of magnitude lower and is much more tractable. Not only that, by extracting the polyhex outline, our algorithm allows searching for nanopores with dimensions and shape factors in a specified range, thus aiding the design of the geometrical properties of nanopores for specific applications. We also provide the coordinate files of the stable nanopores as a library to facilitate future theoretical studies of these nanopores.

Glyphosate Separating and Sensing for Precision Agriculture and Environmental Protection in the Era of Smart Materials.

The present article critically and comprehensively reviews the most recent reports on smart sensors for determining glyphosate (GLP), an active agent of GLP-based herbicides (GBHs) traditionally used in agriculture over the past decades. Commercialized in 1974, GBHs have now reached 350 million hectares of crops in over 140 countries with an annual turnover of 11 billion USD worldwide. However, rolling exploitation of GLP and GBHs in the last decades has led to environmental pollution, animal intoxication, bacterial resistance, and sustained occupational exposure of the herbicide of farm and companies' workers. Intoxication with these herbicides dysregulates the microbiome-gut-brain axis, cholinergic neurotransmission, and endocrine system, causing paralytic ileus, hyperkalemia, oliguria, pulmonary edema, and cardiogenic shock. Precision agriculture, i.e., an (information technology)-enhanced approach to crop management, including a site-specific determination of agrochemicals, derives from the benefits of smart materials (SMs), data science, and nanosensors. Those typically feature fluorescent molecularly imprinted polymers or immunochemical aptamer artificial receptors integrated with electrochemical transducers. Fabricated as portable or wearable lab-on-chips, smartphones, and soft robotics and connected with SM-based devices that provide machine learning algorithms and online databases, they integrate, process, analyze, and interpret massive amounts of spatiotemporal data in a user-friendly and decision-making manner. Exploited for the ultrasensitive determination of toxins, including GLP, they will become practical tools in farmlands and point-of-care testing. Expectedly, smart sensors can be used for personalized diagnostics, real-time water, food, soil, and air quality monitoring, site-specific herbicide management, and crop control.

An advantageous application of molecularly imprinted polymers in food processing and quality control.

In the global market era, food product control is very challenging. It is impossible to track and control all production and delivery chains not only for regular customers but also for the State Sanitary Inspections. Certified laboratories currently use accurate food safety and quality inspection methods. However, these methods are very laborious and costly. The present review highlights the need to develop fast, robust, and cost-effective analytical assays to determine food contamination. Application of the molecularly imprinted polymers (MIPs) as selective recognition units for chemosensors' fabrication was herein explored. MIPs enable fast and inexpensive electrochemical and optical transduction, significantly improving detectability, sensitivity, and selectivity. MIPs compromise durability of synthetic materials with a high affinity to target analytes and selectivity of molecular recognition. Imprinted molecular cavities, present in MIPs structure, are complementary to the target analyte molecules in terms of size, shape, and location of recognizing sites. They perfectly mimic natural molecular recognition. The present review article critically covers MIPs' applications in selective assays for a wide range of food products. Moreover, numerous potential applications of MIPs in the food industry, including sample pretreatment before analysis, removal of contaminants, or extraction of high-value ingredients, are discussed.

A dual role for hepatocyte-intrinsic canonical NF-κB signaling in virus control.

BACKGROUND & AIMS: Hepatic innate immune control of viral infections has largely been attributed to Kupffer cells, the liver-resident macrophages. However, hepatocytes, the parenchymal cells of the liver, also possess potent immunological functions in addition to their known metabolic functions. Owing to their abundance in the liver and known immunological functions, we aimed to investigate the direct antiviral mechanisms employed by hepatocytes. METHODS: Using lymphocytic choriomeningitis virus (LCMV) as a model of liver infection, we first assessed the role of myeloid cells by depletion prior to infection. We investigated the role of hepatocyte-intrinsic innate immune signaling by infecting mice lacking canonical NF-κB signaling (IkkßΔHep) specifically in hepatocytes. In addition, mice lacking hepatocyte-specific interferon-α/ß signaling-(IfnarΔHep), or interferon-α/ß signaling in myeloid cells-(IfnarΔMyel) were infected. RESULTS: Here, we demonstrate that LCMV activates NF-κB signaling in hepatocytes. LCMV-triggered NF-κB activation in hepatocytes did not depend on Kupffer cells or TNFR1 signaling but rather on Toll-like receptor signaling. LCMV-infected IkkßΔHep livers displayed strongly elevated viral titers due to LCMV accumulation within hepatocytes, reduced interferon-stimulated gene (ISG) expression, delayed intrahepatic immune cell influx and delayed intrahepatic LCMV-specific CD8+ T cell responses. Notably, viral clearance and ISG expression were also reduced in LCMV-infected primary hepatocytes lacking IKKß, demonstrating a hepatocyte-intrinsic effect. Similar to livers of IkkßΔHep mice, enhanced hepatocytic LCMV accumulation was observed in livers of IfnarΔHep mice, whereas IfnarΔMyel mice were able to control LCMV infection. Hepatocytic NF-κB signaling was also required for efficient ISG induction in HDV-infected dHepaRG cells and interferon-α/ß-mediated inhibition of HBV replication in vitro. CONCLUSIONS: Together, these data show that hepatocyte-intrinsic NF-κB is a vital amplifier of interferon-α/ß signaling, which is pivotal for strong early ISG responses, immune cell infiltration and hepatic viral clearance. LAY SUMMARY: Innate immune cells have been ascribed a primary role in controlling viral clearance upon hepatic infections. We identified a novel dual role for NF-κB signaling in infected hepatocytes which was crucial for maximizing interferon responses and initiating adaptive immunity, thereby efficiently controlling hepatic virus replication.

Dextrose-Containing Carrier Solution for Hyperthermic Intraperitoneal Chemotherapy: Increased Intraoperative Hyperglycemia and Postoperative Complications.

PURPOSE: Intraoperative hyperglycemia is associated with infectious complications in general surgery patients. This study aimed to determine if the use of lactated Ringer's (LR) carrier solution during hyperthermic intraperitoneal chemotherapy (HIPEC) would lower the incidence of intraoperative hyperglycemia and improve postoperative outcomes when compared with a standard 1.5% dextrose peritoneal dialysate carrier solution. PATIENTS AND METHODS: This is a retrospective cohort study of 134 patients who underwent HIPEC at the University of Colorado. Perioperative glucose levels and outcomes were compared between patients who were perfused with 1.5% dextrose peritoneal dialysate carrier solution (n = 68) versus LR carrier solution (n = 66). RESULTS: The study population consisted of patients undergoing HIPEC for appendiceal (50%), colorectal (34%), mesothelioma (8%), and ovarian cancer (5%). Intraoperative severe hyperglycemia (glucose ≥ 180 mg/dL) was significantly more common among patients perfused with a dextrose-containing carrier solution versus those perfused with LR (88% vs. 21%; p < 0.001). Patients in the dextrose cohort had significantly more severe complications (39% vs. 12%; p = 0.034), infectious complications (35% vs. 15%; p = 0.011), and organ space infections (18% vs. 5%: p = 0.026) than the LR cohort. On multivariable analysis, dextrose-containing carrier solution was significantly associated with an increased risk of postoperative infectious complications (HR 5.16; p = 0.006). CONCLUSIONS: Intraoperative hyperglycemia is common when dextrose-containing carrier solution is used during HIPEC, and severe intraoperative hyperglycemia is strongly associated with an increased risk for infectious of complications following HIPEC. LR carrier solution should be routinely used to reduce intraoperative hyperglycemia and its associated risks.

Protein Determination with Molecularly Imprinted Polymer Recognition Combined with Birefringence Liquid Crystal Detection.

Liquid crystal-based sensors offer the advantage of high sensitivity at a low cost. However, they often lack selectivity altogether or require costly and unstable biomaterials to impart this selectivity. To incur this selectivity, we herein integrated a molecularly imprinted polymer (MIP) film recognition unit with a liquid crystal (LC) in an optical cell transducer. We tested the resulting chemosensor for protein determination. We examined two different LCs, each with a different optical birefringence. That way, we revealed the influence of that parameter on the sensitivity of the (human serum albumin)-templated (MIP-HSA) LC chemosensor. The response of this chemosensor with the (MIP-HSA)-recognizing film was linear from 2.2 to 15.2 µM HSA, with a limit of detection of 2.2 µM. These values are sufficient to use the devised chemosensor for HSA determination in biological samples. Importantly, the imprinting factor (IF) of this chemosensor was appreciable, reaching IF = 3.7. This IF value indicated the predominant binding of the HSA through specific rather than nonspecific interactions with the MIP.

Gender equity and public health outcomes: The COVID-19 experience.

This paper extends the growing research on the impact of gender equity on public health outcomes using the ongoing Covid-19 pandemic as its research setting. Specifically, it introduces a conceptual model incorporating the impact of gender equity and human development on women's representation in legislature and public health expenditure, and their combined impact with human environment (population density, aging population and urban population) on important public health outcomes in the Covid-19 context, including the total number of tests, diagnosed, active and critical cases, and deaths. Data from 210 countries shows support for many of the hypothesized relationships in the conceptual model. The results provide useful insights about the factors that influence the representation of women in political systems around the world and its impact on public health outcomes. The authors also discuss implications for public health policy-makers to ensure efficient and effective delivery of public health services in future.

Managing uncertainty during a global pandemic: An international business perspective.

Despite the perennial need to understand and manage uncertainty in international business, there is no comprehensive framework that incorporates different types of uncertainty, their antecedents and outcomes, and the different coping strategies used by managers and their outcomes. This makes it difficult for international business managers to understand the types of uncertainty in their businesses and develop appropriate strategies to deal with it effectively, especially during times such as the ongoing Covid-19 pandemic. This paper uses an extensive review of the international business literature to address the above research gap by identifying the different types of uncertainty, their antecedents and outcomes, the coping strategies used to mitigate their impact, and the consequences of these actions. The authors also use examples from the current Covid-19 crisis to assess the firms' responses and their consequences. The paper concludes with some implications for international business managers and directions for future research.

Detectable Vesicular Stomatitis Virus (VSV)-Specific Humoral and Cellular Immune Responses Following VSV-Ebola Virus Vaccination in Humans.

In response to the Ebola virus (EBOV) crisis of 2013-2016, a recombinant vesicular stomatitis virus (VSV)-based EBOV vaccine was clinically tested (NCT02283099). A single-dose regimen of VSV-EBOV revealed a safe and immunogenic profile and demonstrated clinical efficacy. While EBOV-specific immune responses to this candidate vaccine have previously been investigated, limited human data on immunity to the VSV vector are available. Within the scope of a phase 1 study, we performed a comprehensive longitudinal analysis of adaptive immune responses to internal VSV proteins following VSV-EBOV immunization. While no preexisting immunity to the vector was observed, more than one-third of subjects developed VSV-specific cytotoxic T-lymphocyte responses and antibodies.

"Gate Effect" in p-Synephrine Electrochemical Sensing with a Molecularly Imprinted Polymer and Redox Probes.

The "gate effect" mechanism for conductive molecularly imprinted polymer (MIP) film coated electrodes was investigated in detail. It was demonstrated that the decrease of the DPV signal for the Fe(CN)64-/Fe(CN)63- redox probe with the increase of the p-synephrine target analyte concentration in solution at the polythiophene MIP-film coated electrode did not originate from swelling or shrinking of the MIP film, as it was previously postulated, but from changes in the electrochemical process kinetics. The MIP-film coated electrode was examined with cyclic voltammetry (CV), differential pulse voltammetry (DPV), electrochemical impedance spectroscopy (EIS), and surface plasmon resonance (SPR). The MIP-film thickness in the absence and in the presence of the p-synephrine analyte was examined with in situ AFM imaging. Moreover, it was demonstrated that doping of the MIP film was not affected by p-synephrine binding in MIP-film molecular cavities. It was concluded that the "gate effect" was most likely caused by changes in radical cation (polaron) mobility in the film.

Selective PQQPFPQQ Gluten Epitope Chemical Sensor with a Molecularly Imprinted Polymer Recognition Unit and an Extended-Gate Field-Effect Transistor Transduction Unit.

A molecularly imprinted polymer (MIP) recognition system was devised for selective determination of an immunogenic gluten octamer epitope, PQQPFPQQ. For that, a thin MIP film was devised, guided by density functional theory calculations, and then synthesized to become the chemosensor recognition unit. Bis(bithiophene)-based cross-linking and functional monomers were used for this synthesis. An extended-gate field-effect transistor (EG-FET) was used as the transduction unit. The EG-FET gate surface was coated with the PQQPFPQQ-templated MIP film, by electropolymerization, to result in a complete chemosensor. X-ray photoelectron spectroscopy analysis confirmed the presence of the PQQPFPQQ epitope, and its removal from the MIP film. The chemosensor selectively discriminated between the octamer analyte and another peptide of the same number of amino acids but with two of them mismatched (PQQQFPPQ). The chemosensor was validated with respect to both the PQQPFPQQ analyte and a real gluten extract from semolina flour. It was capable to determine PQQPFPQQ in the concentration range of 0.5-45 ppm with the limit of detection (LOD) = 0.11 ppm. Moreover, it was capable of determining gluten in real samples in the concentration range of 4-25 ppm with LOD = 4 ppm, which is a value sufficient for discriminating between gluten-free and non-gluten-free food products. The gluten content in semolina flour determined with the chemosensor well correlated with that determined with a commercial ELISA gluten kit. The Langmuir, Freundlich, and Langmuir-Freundlich isotherms were fitted to the epitope sorption data. The sorption parameters determined from these isotherms indicated that the imprinted cavities were quite homogeneous and that the epitope analyte was chemisorbed in them.

Regulatory focus, nutrition involvement, and nutrition knowledge.

Few studies have examined the antecedents of nutrition involvement. Similarly, conflicting results have been recorded on the relationship between nutrition involvement and knowledge, knowledge and dietary behaviors, and nutrition involvement and dietary behaviors. This paper addresses these research gaps by exploring the role of regulatory focus as an antecedent of nutrition involvement. It also examines the effect of nutrition involvement on nutrition knowledge and the effects of both involvement and knowledge on diet adjustment. A large-scale study with 1125 Taiwanese consumers demonstrates a positive effect of promotion focus and no significant effect of prevention focus, on nutrition involvement. Income moderates the effect of promotion focus on nutrition involvement, which in turn has positive effects on nutrition knowledge and diet adjustment. Nutrition knowledge also has a positive effect on diet adjustment. The study clarifies these relationships and provides suggestions to policy making.

A Comprehensive Review of Free Radicals, Antioxidants, and Their Relationship with Human Ailments.

The role of free radicals in various human ailments is well established. Still, the researchers continue to emphasize the involvement of free radicals in these disorders. Antioxidants are being used as an effective tool as a defense against disorders caused by free radicals. This review presents brief detail regarding the nature, types, and sources of free radicals that are of pharmacological interest. A summary of the antioxidants, along with possible mechanisms, has also been incorporated. The role of free radicals and antioxidants in various human disease are also presented.

SGLT1 Deficiency Turns Listeria Infection into a Lethal Disease in Mice.

BACKGROUND: Cellular glucose uptake may involve either non-concentrative glucose carriers of the GLUT family or Na+-coupled glucose-carrier SGLT1, which accumulates glucose against glucose gradients and may thus accomplish cellular glucose uptake even at dramatically decreased extracellular glucose concentrations. SGLT1 is not only expressed in epithelia but as well in tumour cells and immune cells. Immune cell functions strongly depend on their metabolism, therefore we hypothesized that deficiency of SGLT1 modulates the defence against bacterial infection. To test this hypothesis, we infected wild type mice and gene targeted mice lacking functional SGLT1 with Listeria monocytogenes. METHODS: SGLT1 deficient mice and wild type littermates were infected with 1x104 CFU Listeria monocytogenes intravenously. Bacterial titers were determined by colony forming assay, SGLT1, TNF-α, IL-6 and IL-12a transcript levels were determined by qRT-PCR, as well as SGLT1 protein abundance and localization by immunohistochemistry. RESULTS: Genetic knockout of SGLT1 (Slc5a1-/- mice) significantly compromised bacterial clearance following Listeria monocytogenes infection with significantly enhanced bacterial load in liver, spleen, kidney and lung, and significantly augmented hepatic expression of TNF-α and IL-12a. While all wild type mice survived, all SGLT1 deficient mice died from the infection. CONCLUSIONS: SGLT1 is required for bacterial clearance and host survival following murine Listeria infection.