Immunological responses in human papillomavirus 16 E6/E7-transgenic mice to E7 protein correlate with the presence of skin disease

The human papillomavirus (HPV) oncogenes, E6 and E7, are believed to contribute to the development of cervical cancers in women infected with certain HPV genotypes, most notably HPV-16 and HPV-18. Given their expression in tumor tissue, E6 and E7 have been implicated as potential tumor-specific antigens. We have examined an HPV-16 E6- and E7-transgenic mouse lineage for immune responses to these viral oncoproteins. Mice in this lineage express the HPV-16 E6 and E7 genes in their skin and eyes, and on aging, these mice frequently develop squamous cell carcinomas and lenticular tumors. Young transgenic mice, which had measurable E7 protein in the eye but not in the skin, were immunologically naive to E7 protein. They mounted an immune response to E7 on immunization comparable to that of nontransgenic controls, suggesting a lack of immune tolerance to this protein. Older line 19 mice, which are susceptible to skin disease associated with transcription of the E6 and E7 open reading frames, had measurable E7 protein in their skin. These older transgenic mice spontaneously developed antibody responses to endogenous E7 protein, particularly in association with skin disease. Also detected in older mice were delayed-type hypersensitivity responses to E7. These finding parallel the humoral immune response to E7 protein in patients with HPV-associated cervical cancer and suggest that line 19 mice may provide a model for studying the immunobiology of HPV-associated cancers

Eyewitness metamemory predicts identification performance in biased and unbiased line‐ups

Purpose Distinguishing accurate from inaccurate identifications is a challenging issue in the criminal justice system, especially for biased police line-ups. That is because biased line-ups undermine the diagnostic value of accuracy post-dictors such as confidence and decision time. Here, we aimed to test general and eyewitness-specific self-ratings of memory capacity as potential estimators of identification performance that are unaffected by line-up bias. Methods Participants (N = 744) completed a metamemory assessment consisting of the Multifactorial Metamemory Questionnaire and the Eyewitness Metamemory Scale and took part in a standard eyewitness paradigm. Following the presentation of a mock-crime video, they viewed either biased or unbiased line-ups. Results Self-ratings of discontentment with eyewitness memory ability were indicative of identification accuracy for both biased and unbiased line-ups. Participants who scored low on eyewitness metamemory factors also displayed a stronger confidence-accuracy calibration than those who scored high. Conclusions These results suggest a promising role for self-ratings of memory capacity in the evaluation of eyewitness identifications, while also advancing theory on self-assessments for different memory systems

An ex-vivo Human Intestinal Model to Study Entamoeba histolytica Pathogenesis

Amoebiasis (a human intestinal infection affecting 50 million people every year) is caused by the protozoan parasite Entamoeba histolytica. To study the molecular mechanisms underlying human colon invasion by E. histolytica, we have set up an ex vivo human colon model to study the early steps in amoebiasis. Using scanning electron microscopy and histological analyses, we have established that E. histolytica caused the removal of the protective mucus coat during the first two hours of incubation, detached the enterocytes, and then penetrated into the lamina propria by following the crypts of Lieberkühn. Significant cell lysis (determined by the release of lactodehydrogenase) and inflammation (marked by the secretion of pro-inflammatory molecules such as interleukin 1 beta, interferon gamma, interleukin 6, interleukin 8 and tumour necrosis factor) were detected after four hours of incubation. Entamoeba dispar (a closely related non-pathogenic amoeba that also colonizes the human colon) was unable to invade colonic mucosa, lyse cells or induce an inflammatory response. We also examined the behaviour of trophozoites in which genes coding for known virulent factors (such as amoebapores, the Gal/GalNAc lectin and the cysteine protease 5 (CP-A5), which have major roles in cell death, adhesion (to target cells or mucus) and mucus degradation, respectively) were silenced, together with the corresponding tissue responses. Our data revealed that the signalling via the heavy chain Hgl2 or via the light chain Lgl1 of the Gal/GalNAc lectin is not essential to penetrate the human colonic mucosa. In addition, our study demonstrates that E. histolytica silenced for CP-A5 does not penetrate the colonic lamina propria and does not induce the host's pro-inflammatory cytokine secretion

Dissonance-Based Interventions for the Prevention of Eating Disorders: Using Persuasion Principles to Promote Health

The limited efficacy of prior eating disorder (ED) prevention programs led to the development of dissonance-based interventions (DBI) that utilize dissonance-based persuasion principles from social psychology. Although DBIs have been used to change other attitudes and behaviors, only recently have they been applied to ED prevention. This article reviews the theoretical rationale and empirical support for this type of prevention program. Relative to assessment-only controls, DBIs have produced greater reductions in ED risk factors, ED symptoms, future risk for onset of threshold or subthreshold EDs, future risk for obesity onset, and mental health utilization, with some effects persisting through 3-year follow-up. DBIs have also produced significantly stronger effects than alternative interventions for many of these outcomes, though these effects typically fade more quickly. A meta-analysis indicated that the average effects for DBIs were significantly stronger than those for non-DBI ED prevention programs that have been evaluated. DBIs have produced effects when delivered to high-risk samples and unselected samples, as well as in efficacy and effectiveness trials conducted by six independent labs, suggesting that the effects are robust and that DBIs should be considered for the prevention of other problems, such as smoking, substance abuse, HIV, and diabetes care

Protist-Type Lysozymes of the Nematode Caenorhabditis elegans Contribute to Resistance against Pathogenic Bacillus thuringiensis

Pathogens represent a universal threat to other living organisms. Most organisms express antimicrobial proteins and peptides, such as lysozymes, as a protection against these challenges. The nematode Caenorhabditis elegans harbours 15 phylogenetically diverse lysozyme genes, belonging to two distinct types, the protist- or Entamoeba-type (lys genes) and the invertebrate-type (ilys genes) lysozymes. In the present study we characterized the role of several protist-type lysozyme genes in defence against a nematocidal strain of the Gram-positive bacterium Bacillus thuringiensis. Based on microarray and subsequent qRT-PCR gene expression analysis, we identified protist-type lysozyme genes as one of the differentially transcribed gene classes after infection. A functional genetic analysis was performed for three of these genes, each belonging to a distinct evolutionary lineage within the protist-type lysozymes (lys-2, lys-5, and lys-7). Their knock-out led to decreased pathogen resistance in all three cases, while an increase in resistance was observed when two out of three tested genes were overexpressed in transgenic lines (lys-5, lys-7, but not lys-2). We conclude that the lysozyme genes lys-5, lys-7, and possibly lys-2 contribute to resistance against B. thuringiensis, thus highlighting the particular role of lysozymes in the nematode's defence against pathogens

An oxidative approach enables efficient access to cyclic azobenzenes

Azobenzenes are versatile photoswitches that have found widespread use in a variety of fields, ranging from photo-pharmacology to the material sciences. In addition to regular azobenzenes the cyclic diazocines have recently emerged. Although diazocines have fascinating conformational and photophysical properties, their use has been limited by their synthetic accessibility. Herein, we present a general, high-yielding protocol that relies on the oxidative cyclization of diani-lines. In combination with a modular substrate synthesis, it allows for rapid access to diversely functionalized diazocines on gram scales. Our work systematically explores substituent effects on the photoisomerization and thermal relaxation of diazocines. It will enable their incorporation into a wide variety of functional molecules, unlocking the full potential of these emerging photoswitches. The method can be applied to the synthesis of a new cyclic azobenzene with a nine-membered central ring and distinct properties

Transformation of receptor tyrosine kinases into glutamate receptors and photoreceptors

Receptor tyrosine kinases (RTKs) are key regulators of cellular functions in metazoans. In vertebrates, RTKs are mostly activated by polypeptides but are not naturally sensitive to amino acids or light. Taking inspiration from Venus Kinase Receptors (VKRs), an atypical family of RTKs found in Nature, we have achieved the transformation of the human insulin (hIR) and hepatocyte growth factor receptor (hMET) into glutamate receptors by replacing their extracellular binding domains with the ligand‐binding domain of metabotropic glutamate receptor type 2 (mGluR2). We then imparted light sensitivity by covalent attachment of a synthetic, glutamate‐based photoswitch onto a self‐labelling SNAP tag. Employing a Xenopus laevis oocyte kinase activity assay, we demonstrate how these chimeric RTKs, termed LihIR (Light‐controlled human Insulin Receptor) and LihMET (Light‐controlled human MET Receptor), can be used to exert optical control over insulin or MET signaling pathways. Our results outline a potentially general strategy to convert RTKs into photoreceptors