人乳头瘤病毒16通过DNA甲基化和组蛋白修饰路径的致癌机制研究进展

许多研究表明,人乳头瘤病相关肿瘤中存在DNA甲基化、组蛋白修饰等各种表观遗传学改变。在这些表观遗传学改变的研究中,提示E6和E7可能对人乳头瘤病毒相关肿瘤的DNA甲基化及组蛋白修饰存在直接或间接的影响。其中一个重要的机制可能是E6和E7直接与上述表观遗传学路径中涉及的相关蛋白酶相互作用。进一步明确E6、E7通过DNA甲基化和组蛋白修饰路径的致癌机制。     

A novel TMEM16A splice variant lacking the dimerization domain contributes to calcium‐activated chloride secretion in human sweat gland epithelial cells

Sweating is an important physiological process to regulate body temperature in humans, and various disorders are associated with dysregulated sweat formation. Primary sweat secretion in human eccrine sweat glands involves Ca²⁺‐activated Cl^? channels (CaCC). Recently, members of the TMEM16 family were identified as CaCCs in various secretory epithelia; however, their molecular identity in sweat glands remained elusive. Here, we investigated the function of TMEM16A in sweat glands. Gene expression analysis revealed that TMEM16A is expressed in human NCL‐SG3 sweat gland cells as well as in isolated human eccrine sweat gland biopsy samples. Sweat gland cells express several previously described TMEM16A splice variants, as well as one novel splice variant, TMEM16A(acΔe3) lacking the TMEM16A‐dimerization domain. Chloride flux assays using halide‐sensitive YFP revealed that TMEM16A is functionally involved in Ca²⁺‐dependent Cl^? secretion in NCL‐SG3 cells. Recombinant expression in NCL‐SG3 cells showed that TMEM16A(acΔe3) is forming a functional CaCC, with basal and Ca²⁺‐activated Cl^? permeability distinct from canonical TMEM16A(ac). Our results suggest that various TMEM16A isoforms contribute to sweat gland‐specific Cl^? secretion providing opportunities to develop sweat gland‐specific therapeutics for treatment of sweating disorders.     

Behavioral changes and hyperglycemia in NODEF mice following bisphenol S exposure are affected by diets

Bisphenol S (BPS), an analogue of the controversial bisphenol A (BPA) that is found in epoxy resins and plastics, is a potential endocrine-disrupting chemical that can mimic endogenous hormone signaling. However, little is known about the behavioral or immunologic effects of BPS. The purpose of this study was to examine the impact of diets in BPS-treated mice in relation to hyperglycemia, development of type 1 diabetes, immunomodulation, and behavioral changes. Adult male and female nonobese diabetic excluded flora (NODEF) mice were exposed to environmentally relevant doses of BPS (VH, 30, or 300 μg/kg BW) and fed either a soy-based diet, a phytoestrogen-free diet, or a Western diet. NODEF male mice fed a soy-based diet exhibited a decreased curiosity/desire to explore, and possibly increased anxiety-like behavior and decreased short-term memory when exposed to BPS (300 μg/kg BW). In addition, these mice had significant increases in non-fasting blood glucose levels along with increased insulin sensitivity, impaired glucose tolerance, resistance to fasting and proinflammation. Although BPS had little effect on the glucose parameters in NODEF male mice fed a Western diet, there were decreases in %CD24⁺CD5⁺ and %B220⁺CD40L^–cell populations and increases in distance traveled during the novel object test, suggesting hyperactivity. NODEF females fed a phytoestrogen-free diet exhibited slight decreases in time spent immobile during the tail suspension test in both the 30 and 300 μg/kg BW dose groups along with increases in %CD4⁺CD8⁺ and %Mac3⁺CD45R⁺ cell populations, signifying increased hyperactivity and anxiety-like behavior. In conclusion, BPS-exposed NODEF mice exhibited sex and diet-related changes in hyperglycemia, behaviors and immune endpoints.     

Constitution du champ psychanalytique

ObjectivesThe purpose of this paper is to situate the emergence of psychoanalysis; its differentiation from clinical psychiatry; and its constitution as a specific field of practice and knowledge in the context of the modern, Cartesian conception of the autonomous subject.MethodThe methods used include textual critic, the genealogy of concepts and their contextualization in the history of the foundational doctrines and ideas of modernity.ResultsBy its constitutive postulates, in particular organicism, psychiatry is deeply rooted in the foundational paradigm of modernity, which opposes a consciousness-centered subject, defined by her/his liberty, to a geometrized material universe, submitted to a strict mechanical determinism. With the concept of the Unconscious, psychoanalysis has always positioned itself in opposition to an objectifying approach of psychopathology, which translatesdirectly into an interrogation of the organicist postulate.DiscussionFreudian theory, however, borrows its main models from rationalist psychology, whose constitutive principles are a direct tributary of the now partly obsolete paradigm of classical science. Jung will vigorously object to that, but without success, largely because of the regressive and mystical character of his conceptualization.ConclusionsIt is not until the arrival of the post-Freudians, most importantly Lacan, that the heteronomous causation of the subject can be laid; thus, psychoanalysis can find the doctrinal framework that will allow it, with the formulation of structural theory, to address causality in psychopathology.     

The effect of two different bracket types on the salivary levels of S mutans and S sobrinus in the early phase of orthodontic treatment

Objective:To determine the difference in the levels of Streptococcus mutans and S sobrinus in stimulated saliva in orthodontic patients with different bracket types (stainless steel and esthetic brackets) using polymerase chain reaction and cultivation method.Materials and Methods:Thirty-two patients, aged 13 to 30 years, were selected following these criteria: 1) orthodontic treatment indication, 2) systemic health, and 3) no tobacco and antibiotic consummation for three months prior to the commencement of the study. Patients were divided into two groups according to the bracket type; 16 patients formed the conventional bracket group (stainless steel brackets), and 16 patients formed the esthetic bracket group (plastic brackets). The levels of S mutans and S sobrinus in stimulated whole saliva samples were collected prior to fixed orthodontic appliance placement (T1) and 12 weeks after placement (T2), as were the Decayed, Missing, and Filled Surface Index (DMFS) and Oral Hygiene Index-Simplified (OHI-S). Mann-Whitney, Wilcoxon, and chi-square tests were used for statistical analysis.Results:Statistical analysis (chi-square test) showed no difference in S mutans and S sobrinus counts among patients with different brackets at either T1 or T2. There was no difference in total bacteria counts after fixed orthodontic appliance placement.Conclusion:The number of colony-forming units of S mutans and S sobrinus in stimulated saliva samples does not seem to be significantly different between patients with stainless steel brackets and patients with plastic brackets.     

A 16q22.2-q23.1 deletion identified in a male infant with West syndrome

In partial monosomy of the distal part of chromosome 16q, abnormal facial features, intellectual disability (ID), and feeding dysfunction are often reported. However, seizures are not typical and the majority of them were seizure-free. Here we present the case of a 16q22.2-q23.1 interstitial deletion identified in a male patient with severe ID, facial anomalies including forehead protrusions and flat nose bridge, patent ductus arteriosus, bilateral vocal cord atresia treated by tracheotomy, and West syndrome, which were developed 10 months after birth. Although phenobarbital, sodium valproate (VPA), and zonisamide were not effective as monotherapies or combination therapies, the patient's epileptic seizures and electroencephalogram anomalies disappeared following combined therapy with lamotrigine and VPA. Although WW Domain Containing Oxidoreductase (WWOX), which is known as a cause of autosomal recessive epileptic encephalopathy, was included within the 6.8-Mb deleted region which identified by targeted panel sequencing and validated by chromosomal microarray analysis, no pathogenic variants were detected in the other allele of WWOX. Therefore, it is possible that other genes within or outside of the long deleted region or their interactions may cause West syndrome in this patient.     

Alterations in cortical and thalamic connections of somatosensory cortex following early loss of vision

Early loss of vision produces dramatic changes in the functional organization and connectivity of the neocortex in cortical areas that normally process visual inputs, such as the primary and second visual area. This loss also results in alterations in the size, functional organization, and neural response properties of the primary somatosensory area, S1. However, the anatomical substrate for these functional changes in S1 has never been described. In the present investigation, we quantified the cortical and subcortical connections of S1 in animals that were bilaterally enucleated very early in development, prior to the formation of retino-geniculate and thalamocortical pathways. We found that S1 receives dense inputs from novel cortical fields, and that the density of existing cortical and thalamocortical connections was altered. Our results demonstrate that sensory systems develop in tandem and that alterations in sensory input in one system can affect the connections and organization of other sensory systems. Thus, therapeutic intervention following early loss of vision should focus not only on restoring vision, but also on augmenting the natural plasticity of the spared systems.     

Left ventricular aneurysms associated with intraoperative venting of the cardiac apex in children

Left ventricular (LV) apical aneurysms were observed in 16 of 50 (32%) children (average age 8 years) consecutively catheterized after surgical repair of congenital heart disease. The LV apex was vented by a sump during cardiopulmonary bypass in each. The aneurysms varied in size, but were generally small. Average dimensions were 7.5 × 6.8 mm in the anteroposterior projection and 8.9 × 5.7 mm in the left anterior oblique projection. The LV apex wall was thinner in patients with aneurysms than in age- and lesion-matched controls. All of the LV aneurysm patients were asymptomatic during average follow-up of 4 years. Nevertheless, such aneurysms are anticipated to represent a potential source of cardiovascular complications and, when possible, alternate methods for venting the left ventricle are recommended.