Survivin in autoimmune diseases

Publication date: Available online 28 May 2017
Source:Autoimmunity Reviews
Author(s): G. Gravina, C. Wasen, M.J. Garcia-Bonete, M. Turkkila, M.C. Erlandsson, S. Töyrä Silfverswärd, M. Brisslert, R. Pullerits, K.M. Andersson, G. Katona, M.I. Bokarewa
Survivin is a protein functionally important for cell division, apoptosis, and possibly, for micro-RNA biogenesis. It is an established marker of malignant cell transformation. In non-malignant conditions, the unique properties of survivin make it indispensable for homeostasis of the immune system. Indeed, it is required for the innate and adaptive immune responses, controlling differentiation and maintenance of CD4⁺ and CD8⁺ memory T-cells, and in B cell maturation. Recently, survivin has emerged as an important player in the pathogenesis of autoimmune diseases. Under the conditions of unreserved inflammation, survivin enhances antigen presentation, maintains persistence of autoreactive cells, and supports production of autoantibodies. In this context, survivin takes its place as a diagnostic and prognostic marker in rheumatoid arthritis, psoriasis, systemic sclerosis and pulmonary arterial hypertension, neuropathology and multiple sclerosis, inflammatory bowel diseases and oral lichen planus. In this review, we summarise the knowledge about non-malignant properties of survivin and focus on its engagement in cellular and molecular pathology of autoimmune diseases. The review highlights utility of survivin measures for clinical applications. It provides rational for the survivin inhibiting strategies and presents results of recent reports on survivin inhibition in modern therapies of cancers and autoimmune diseases.



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Comparative Clinical Characteristics and Natural History of Three Variants of Sclerosing Cholangitis: IgG4-Related SC, PSC/AIH and PSC alone

Publication date: Available online 28 May 2017
Source:Autoimmunity Reviews
Author(s): Min Lian, Bo Li, Xiao Xiao, Yue Yang, Pan Jiang, Li Yan, Chunyan Sun, Jun Zhang, Yiran Wei, Yanmei Li, Weihua Chen, Xiang Jiang, Qi Miao, Xiaoyu Chen, Dekai Qiu, Li Sheng, Jing Hua, Ruqi Tang, Qixia Wang, M. Eric Gershwin, Xiong Ma
There is increased interest and recognition of the clinical variants of Sclerosing Cholangitis (SC) namely IgG4-SC, PSC/AIH overlap and PSC. For most Centers, the characteristic of IgG4-SC has not been thoroughly clinically compared with other Sclerosing Cholangitis variants. Further there are relatively few PSC/AIH overlap patients and the clinical outcome is not well characterized, especially for the PSC/AIH overlap syndrome. Our objective herein is to review and clarify the differences and similarities of the natural history of IgG4-SC, the PSC/AIH overlap and PSC alone. We also place in perspective the diagnostic value of serum IgG4 for IgG4-SC and investigate biomarkers for predicting the prognosis of Sclerosing Cholangitis. In this study, we took advantage of our large and well-defined patient cohort to perform a retrospective cohort study including 57 IgG4-SC, 36 PSC/AIH overlap patients, and 55 PSC patients. Firstly, as expected, we noted significant differences amongst immunoglobulin profiles and all patients exhibited similar cholestatic profiles at presentation. Cirrhotic events were found in 20 of total 57 IgG4-SC, 15 of 36 PSC/AIH overlap, and 18 of 55 PSC patients. Serum IgG4 was elevated in 92.65% of IgG4-SC patients with an 86% sensitivity and 98% specificity for diagnosis. IgG4-SC patients had a better treatment response at 6-month and 1-year than PSC/AIH patients, while the latter responded better with steroids than PSC patients. Importantly the adverse outcome-free survival of IgG4-SC patients was reduced, unlike earlier reports, and therefore similar to the PSC/AIH overlap syndrome. Serum IgG and total bilirubin were useful to predict long-term survival of IgG4-SC and PSC/AIH, respectively. In conclusion, serum IgG4 ≧ 1.25 ULN shows an excellent predictability to distinguish IgG4-SC among SC patients. IgG4-SC appears to be immune-mediated inflammatory process, while PSC/AIH overlap more tends to be cholestatic disease.



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Repeated pulses of methyl-prednisolone with reduced doses of prednisone improve the outcome of class III, IV and V lupus nephritis: An observational comparative study of the Lupus-Cruces and lupus-Bordeaux cohorts

Publication date: Available online 28 May 2017
Source:Autoimmunity Reviews
Author(s): Guillermo Ruiz-Irastorza, Amaia Ugarte, Cecile Saint-Pastou, Estibaliz Lazaro, Amalur Iza, Lionel Couzi, Ramon Saenz, Christophe Richez, Sabrina Porta, Patrick Blanco
ObjectiveTo compare the clinical course of patients with class III, IV and V lupus nephritis (LN) treated at Hospital Universitario Cruces (CC) and at Bordeaux University Hospital (BC).MethodsThe Lupus-Cruces nephritis protocol combines pulses of 125mg of methyl-prednisolone with each fortnightly pulse of cyclophosphamide and prednisone ≤30mg/day with tapering over 12–14weeks until 2.5–5mg/day. The BC followed international lupus nephritis guidelines, combining high-dose prednisone and either mycophenolate mofetil or cyclophosphamide, followed by maintenance therapy with low dose prednisone and immunosuppressive drugs. The main outcomes were complete renal remission (CR) and glucocorticoid toxicity.Results44 patients from BC and 29 CC were included. The mean maximum prednisone dose was 42.5 (BC) vs. 21mg/day (CC), p<0.001. The average 6-month prednisone dose was 21 (BC) vs. 8.3mg/d (CC), p<0.001.The mean number of methyl-prednisolone pulses was 3 (BC) vs. 9.3 (CC), p<0.001. HCQ was used by 64% (BC) vs. 100% (CC), p<0.001.CR rates were 30% (BC) vs. 69% (CC), p=0.001, and 42% (BC) vs. 86% (CC), p<0.001, at 6 and 12months, respectively. Patients from the CC more frequently achieved CR (adjusted HR 3.8, 95%CI 2.05–7-09). The number of pulses of methyl-prednisolone were associated with CR (adjusted HR 1.09, 95%CI 1.03–1.15). Patients in the CC had a lower risk of GC-related side effects (adjusted HR 0.19, 95%CI 0.04–0.89).ConclusionThe Lupus-Cruces nephritis protocol improves the outcome of LN. Repeated methyl-prednisolone pulses help reduce the dose of oral glucocorticoids and enhance clinical response.



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Very Early and Early Systemic Sclerosis in the Spanish Scleroderma Registry (RESCLE) Cohort

Publication date: Available online 28 May 2017
Source:Autoimmunity Reviews
Author(s): Luis Trapiella Martínez, José Bernardino Díaz López, Luis Caminal Montero, Carles Tolosa Vilella, Alfredo Guillén del Castillo, Dolores Colunga Argüelles, Manuel Rubio Rivas, Nerea Iniesta Arandia, María Jesús Castillo Palma, Luis Sáez Comet, María Victoria Egurbide Arberas, Norberto Ortego-Centeno, Mayka Freire, Jose Antonio Vargas Hitos, Juan José Ríos Blanco, Jose Antonio Todolí Parra, Mónica Rodríguez Carballeira, Adela Marín Ballvé, Antonio Javier Chamorro Fernández, Xavier Pla Salas, Ana Belén Madroñero Vuelta, Manuel Ruiz Muñoz, Vicent Fonollosa Pla, Carmen Pilar Simeón Aznar
ObjectivesAccording to the existence of subclinical organ involvement pre-scleroderma should be divided into two subsets: very early and early disease. Pre-scleroderma patients included in the Spanish Scleroderma Registry (RESCLE) Cohort were reclassified into subsets. Differences were evaluated and the risk of progression to definite systemic sclerosis was estimated.MethodsThe characteristics of very early and early SSc patients were compared. A logistic regression model was used to determine the risk factors of progression.Results1632 patients were included, 36 (2.2%) in the very early subset and 111 (6.8%) in the early subset. There were no differences in sex, age at disease onset, duration of Raynaud's phenomenon, antinuclear antibodies or capillaroscopic findings. Three (8.3%) very early SSc patients evolved to definite SSc, 2 (5.6%) of them meeting the ACR/EULAR 2013 criteria, unlike 31 (28%) early SSc patients, 20 (24%) of them meeting the criteria (p=0.034). Digestive involvement was an independent risk factor of progression (OR 17; 95% CI, 6.1–47.2).ConclusionsThe classification of early forms of scleroderma identifies patients with different prognostic risk of progression. The evolution to definite SSc is more frequent in early than in very early SSc patients. Digestive involvement is a risk factor of progression. An active assessment of organ damage in preclinical stages allows a correct classification and risk stratification, with implications for monitoring and treatment.



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Recent advances in our understanding of giant cell arteritis pathogenesis

Publication date: Available online 28 May 2017
Source:Autoimmunity Reviews
Author(s): Maxime Samson, Marc Corbera-Bellalta, Sylvain Audia, Ester Planas-Rigol, Laurent Martin, Maria Cinta Cid, Bernard Bonnotte
Giant cell arteritis (GCA) is a granulomatous vasculitis affecting large arteries, especially the aorta and the extracranial branches of the external carotid artery. Its exact pathogenesis is not fully understood but major progress has been made in recent years, leading to new therapeutic targets like inhibition of the interleukin-6 pathway or the modulation of immune checkpoints. The cause of GCA has not been clearly identified but it is thought that GCA occurs on a genetic background and is triggered by unknown environmental factors that could activate and lead to the maturation of dendritic cells localized in the adventitia of normal arteries. These activated dendritic cells then produce chemokines which trigger the recruitment of CD4⁺ T cells, which in turn become activated, proliferate and polarize into Th1 and Th17 cells, which produce IFN-γ and IL-17, respectively. Exposed to IFN-γ, endothelial cells and vascular smooth muscle cells produce chemokines leading to the recruitment of further Th1 cells, CD8⁺ T cells and monocytes. The latter differentiate into macrophages, which, when persistently exposed to IFN-γ, form giant cells, the histological hallmark of GCA. With the contribution of vascular smooth muscle cells, immune cells then trigger the destruction and remodeling of the arterial wall, thus leading to the formation of a neo-intima resulting in progressive occlusion of the arterial lumen, which is responsible for the ischemic symptoms of GCA. In this paper, we review recent progress in our understanding of GCA pathogenesis in the fields of genetics, epigenetics, infections, immunology and vascular remodeling.



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Neurobiological mechanisms of state-dependent learning

Publication date: August 2017
Source:Current Opinion in Neurobiology, Volume 45
Author(s): Jelena Radulovic, Vladimir Jovasevic, Mariah AA Meyer
State-dependent learning (SDL) is a phenomenon relating to information storage and retrieval restricted to discrete states. While extensively studied using psychopharmacological approaches, SDL has not been subjected to rigorous neuroscientific study. Here we present an overview of approaches historically used to induce SDL, and highlight some of the known neurobiological mechanisms, in particular those related to inhibitory neurotransmission and its regulation by microRNAs (miR). We also propose novel cellular and circuit mechanisms as contributing factors. Lastly, we discuss the implications of advancing our knowledge on SDL, both for most fundamental processes of learning and memory as well as for development and maintenance of psychopathology.



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Neural immunoglobulin superfamily interaction networks

Publication date: August 2017
Source:Current Opinion in Neurobiology, Volume 45
Author(s): Kai Zinn, Engin Özkan
The immunoglobulin superfamily (IgSF) encompasses hundreds of cell surface proteins containing multiple immunoglobulin-like (Ig) domains. Among these are neural IgCAMs, which are cell adhesion molecules that mediate interactions between cells in the nervous system. IgCAMs in some vertebrate IgSF subfamilies bind to each other homophilically and heterophilically, forming small interaction networks. In Drosophila, a global 'interactome' screen identified two larger networks in which proteins in one IgSF subfamily selectively interact with proteins in a different subfamily. One of these networks, the 'Dpr-ome', includes 30 IgSF proteins, each of which is expressed in a unique subset of neurons. Recent evidence shows that one interacting protein pair within the Dpr-ome network is required for development of the brain and neuromuscular system.



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Dual-Energy Computed Tomography: Applications in Neurologic, Head, and Neck Imaging

Publication date: Available online 27 May 2017
Source:Neuroimaging Clinics of North America
Author(s): Suresh K. Mukherji




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Anti-inflammatory effect of epigallocatechin gallate in a mouse model of ovalbumin-induced allergic rhinitis

Publication date: August 2017
Source:International Immunopharmacology, Volume 49
Author(s): Meng Fu, Shulian Fu, Saihong Ni, Liyuan Zou, Yumei Liu, Tie Hong
Currently, a variety of studies have demonstrated that green tea has anti-allergic properties, and the major polyphenolic compound, epigallocatechin gallate (EGCG), plays a significant role. Some research indicates that EGCG reduces the production and expression of allergy-related substances. Therefore, EGCG has a potential effect of reducing allergic rhinitis (AR). In this study, the effect of EGCG on allergic rhinitis in an ovalbumin (OVA)-induced mouse model was investigated. After administration of EGCG, the number of sneezes and the occurrence of nasal rubbing were significantly decreased, the concentrations of immunoglobulin E (IgE) and histamine were suppressed in AR mouse serum, the levels of interleukin (IL)-1β, IL-4, and IL-6 were reduced in AR mice nasal lavage fluid (NLF), and the nasal mucosa mRNA and protein expression of cyclooxygenase 2 (COX-2), IL-1β, IL-4, and IL-6 were inhibited. The data indicate that EGCG has a beneficial effect of reducing allergic rhinitis.



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Indirect comparison between pembrolizumab and nivolumab for the treatment of non-small cell lung cancer: A meta-analysis of randomized clinical trials

Publication date: August 2017
Source:International Immunopharmacology, Volume 49
Author(s): Tzu-Rong Peng, Fang-Pei Tsai, Ta-Wei Wu
ObjectiveThe purpose of this study is to evaluate the efficacy and adverse effects of nivolumab and pembrolizumab for the treatment of advanced non-small-cell lung cancer (NSCLC) by meta-analysis.Materials and methodsThis meta-analysis of randomized controlled trials (RCTs) was performed after searching PubMed, EMBASE, and American Society of Clinical Oncology meeting abstracts, clinicaltrial gov, and Cochrane library databases. Two reviewers independently assessed the quality of the trials. Outcomes analysis was overall response rates (ORR), overall survival (OS), progression- free survival (PFS) and major adverse effects with odds ratio (OR) or hazard ratio (HR) and 95% confidence intervals (CI).ResultsResults reported from three RCTs involving 1,887 patients are included in this analysis. Indirect comparison between pembrolizumab and nivolumab in advanced NSCLC shows no statistically significant difference in ORR (OR: 1.14, 95% CI, 0.60–2.01), OS (HR: 0.98, 95% CI, 0.35–2.74) and PFS (HR: 1.12, 95% CI, 0.70–1.77). The incidence of grades≥3 adverse effects is higher with pembrolizumab as compared with nivolumab (OR: 3.44, 95% CI, 1.87–6.32). There are no significant statistical differences between severe adverse effects, such as pneumonitis and hypothyroidism, of the two drugs.ConclusionsThis study has demonstrated that pembrolizumab and nivolumab have similar survival outcomes in patients with advanced NSCLC, but pembrolizumab has a higher incidence of grades≥3 adverse effects than nivolumab.



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Colorectal tumors are enriched with regulatory plasmablasts with capacity in suppressing T cell inflammation

Publication date: August 2017
Source:International Immunopharmacology, Volume 49
Author(s): Hui Mao, Fei Pan, Zhiyong Wu, Zhikuan Wang, Yanhua Zhou, Pengfei Zhang, Miaomiao Gou, Guanghai Dai
Inflammation plays a critical role in the initiation of colorectal cancer but is also required to mediate antitumor immunity in established tumors. Therefore, identifying the cellular and molecular components in colorectal tumors is necessary for the understanding of tumor progression and the development of novel treatment strategies. In this study, we demonstrated that a specific subtype of regulatory B cells, the CD19^loCD27^hi plasmablasts, was enriched in the colorectal tumor microenvironment. This CD19^loCD27^hi plasmablast subset presented high interleukin 10 (IL-10) expression but not transforming growth factor-β (TGF-β) secretion. Phenotypically, the tumor-infiltrating IL-10⁺ CD19^loCD27^hi plasmablasts presented lower CD24, CD38, and IgA, and higher Tim-1 and IgG expression compared to the IL-10⁻ CD19^loCD27^hi plasmablasts. The tumor-infiltrating IL-10⁺ CD19^loCD27^hi plasmablasts were found to be gut-homing due to their higher expression of α4β7 while peripheral blood B cells did not show the same characteristic. When cocultured with autologous T cells, CD19^loCD27^hi plasmablasts demonstrated potent activity in suppressing interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) expression but did not promote Foxp3 expression. Overall, this study demonstrate that in colorectal cancer, CD19^loCD27^hi plasmablasts make up a large percentage in tumor-infiltrating lymphocytes and possess potent immunoregulatory functions, and thus could be utilized in future therapeutic strategies.



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Leukocyte Breaching of Endothelial Barriers: The Actin Link

Publication date: Available online 27 May 2017
Source:Trends in Immunology
Author(s): Ronen Alon, Jaap D. van Buul
Leukocyte transendothelial migration (TEM) takes place across micron-wide gaps in specific post-capillary venules generated by the transmigrating leukocyte. Because endothelial cells contain a dense cytoskeletal network, transmigrating leukocytes must overcome these mechanical barriers as they squeeze their nuclei through endothelial gaps and pores. Recent findings suggest that endothelial cells are not a passive barrier, and upon engagement by transmigrating leukocytes trigger extensive dynamic modifications of their actin cytoskeleton. Unexpectedly, endothelial contractility functions as a restrictor of endothelial gap enlargement rather than as a facilitator of gap formation as was previously suggested. In this review we discuss current knowledge regarding how accurately timed endothelial actin-remodeling events are triggered by squeezing leukocytes and coordinate leukocyte TEM while preserving blood vessel integrity.



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Novel Approaches to Analyze Immunoglobulin Repertoires

Publication date: Available online 26 May 2017
Source:Trends in Immunology
Author(s): Hedda Wardemann, Christian E. Busse
Analysis of immunoglobulin (Ig) repertoires aims to comprehend Ig diversity with the goal of predicting humoral immune responses in the context of infection, vaccination, autoimmunity, and malignancies. The first next-generation sequencing (NGS) analyses of bulk B cell populations dramatically advanced sampling depth over previous low-throughput single-cell-based protocols, albeit at the expense of accuracy and loss of chain-pairing information. In recent years the field has substantially differentiated, with bulk analyses becoming more accurate while single-cell approaches have gained in throughput. Additionally, new platforms striving to combine high throughput and chain pairing have been developed as well as various computational tools for analysis. Here we review the developments of the past 4–5 years and discuss the open challenges.



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Heart rate changes according to the complexity of motor events in REM sleep behavior disorder

Publication date: July 2017
Source:Clinical Neurophysiology, Volume 128, Issue 7
Author(s): Paulo Bugalho, Marcelo Mendonça




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Changes in resting-state directed connectivity in cortico-subcortical networks correlate with cognitive function in Parkinson’s disease

Publication date: July 2017
Source:Clinical Neurophysiology, Volume 128, Issue 7
Author(s): Lennard I. Boon, Arjan Hillebrand, Kim T.E. Olde Dubbelink, Cornelis J. Stam, Henk W. Berendse
ObjectiveThe pathophysiological mechanisms underlying Parkinson's disease (PD)-related cognitive decline and conversion to PD dementia are poorly understood. In the healthy human brain, stable patterns of posterior-to-anterior cortical information flow have recently been demonstrated in the higher frequency bands using magnetoencephalography (MEG). In this study we estimated PD-related changes in information flow patterns, as well as the contribution of subcortical regions.MethodsResting-state MEG recordings were acquired in moderately advanced PD patients (n=34; mean Hoehn and Yahr-stage 2.5) and healthy controls (n=12). MEG signals were projected to both cortical and subcortical brain regions, following which we estimated the balance between incoming and outgoing information flow per region.ResultsIn PD patients, compared to controls, preferential beta band information outflow was significantly higher for the basal ganglia and frontotemporal cortical regions, and significantly lower for parieto-occipital regions. In addition, in patients, low preferential information outflow from occipital regions correlated with poor global cognitive performance.ConclusionIn the PD brain, a shift in balance towards more anterior-to-posterior beta band information flow takes place and is associated with poorer cognitive performance.SignificanceOur results indicate that a reversal of the physiological posterior-to-anterior information flow may be an important mechanism in PD-related cognitive decline.



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Flexion synergy overshadows flexor spasticity during reaching in chronic moderate to severe hemiparetic stroke

Publication date: July 2017
Source:Clinical Neurophysiology, Volume 128, Issue 7
Author(s): Michael D. Ellis, Ingrid Schut, Julius P.A. Dewald
ObjectivePharmaceutical intervention targets arm flexor spasticity with an often-unsuccessful goal of improving function. Flexion synergy is a related motor impairment that may be inadvertently neglected. Here, flexor spasticity and flexion synergy are disentangled to determine their contributions to reaching dysfunction.MethodsTwenty-six individuals participated. A robotic device systematically modulated shoulder abduction loading during ballistic reaching. Elbow muscle electromyography data were partitioned into windows delineated by elbow joint velocity allowing for the separation of synergy- and spasticity-related activation.ResultsReaching velocity decreased with abduction loading (p<0.001) such that velocity was 30% slower when lifting the arm at 50% of abduction strength compared to when arm weight was supported. Abnormal flexion synergy increased with abduction loading (p<0.001) such that normalized activation ranged from a median (interquartile range) of 0.07 (0.03–0.12) when arm weight was supported to 0.19 (0.12–0.40) when actively lifting (large effect size, d=0.59). Flexor spasticity was detected during reaching (p=0.016) but only when arm weight was supported (intermediate effect size, d=0.33).ConclusionFlexion synergy is the predominant contributor to reaching dysfunction while flexor spasticity appears only relevant during unnaturally occurring passively supported movement.SignificanceInterventions targeting flexion synergy should be leveraged in future stroke recovery trials.



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Macrodactylia lipomatosa with fibrolipomatous hamartomas: Macroscopic and ultrasound clues

Publication date: July 2017
Source:Clinical Neurophysiology, Volume 128, Issue 7
Author(s): Daniel Weiss, Brigitte Zrenner, Stefan Wolking, Tobias Freilinger, Alexander Grimm




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Uterine ERα epigenetic modifications are induced by the endocrine disruptor endosulfan in female rats with impaired fertility

Publication date: Available online 27 May 2017
Source:Molecular and Cellular Endocrinology
Author(s): María M. Milesi, Jorgelina Varayoud, Jorge G. Ramos, Enrique H. Luque
High ERα activity may disrupt the window of uterine receptivity, causing defective implantation. We investigated whether implantation failures prompted by endosulfan are associated with aberrant ERα uterine expression and DNA methylation status during the pre-implantation period. ERα-dependent target genes that play a crucial role in the uterine receptivity for embryo attachment and implantation were also investigated. Newborn female rats received corn oil (vehicle, Control), 6 μg/kg/d of endosulfan (Endo6) or 600 μg/kg/d of endosulfan (Endo600) on postnatal days (PND) 1, 3, 5, and 7. On PND90, females were made pregnant and on gestational day 5 (GD5, pre-implantation period) uterine samples were collected. ERα expression was assessed at protein and mRNA levels by immunohistochemistry and real time RT-PCR, respectively. ERα transcript variants mRNA containing alternative 5'-untranslated regions (5′UTRs) were also evaluated. We searched for predicted transcription factors binding sites in ERα regulatory regions and assessed their methylation status by Methylation-Sensitive Restriction Enzymes-PCR technique (MSRE-PCR). The expression of the ERα-dependent uterine target genes, i.e. mucin-1 (MUC-1), insulin-like growth factor-1 (IGF-1), and leukemia inhibitory factor (LIF), was assessed by real time RT-PCR. Both doses of endosulfan increased the expression of ERα and its transcript variants ERα-OS, ERα-O, ERα-OT and ERα-E1. Moreover, a decreased DNA methylation levels were detected in some ERα regulatory regions, suggesting an epigenetic up-regulation of it transcription. ERα overexpression was associated with an induction of its downstream genes, MUC-1 and IGF-1, suggesting that endosulfan might alter the uterine estrogenic pathway compromising uterine receptivity. These alterations could account, at least in part, for the endosulfan-induced implantation failures.



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Methylation dictates PI.f-specific CYP19 transcription in human glial cells

Publication date: Available online 27 May 2017
Source:Molecular and Cellular Endocrinology
Author(s): Wenjuan Tan, Zhiping Zhu, Lan Ye, Lai K. Leung
CYP19 is the single copy gene encoding for the estrogen synthetic enzyme aromatase. Alternate splicing of the promoter is the regulatory mechanism of this gene. In the brain, estrogen is synthesized in neuronal and glial cells and the gene is mainly regulated by the alternate promoter PI.f. The hormone produced in this vicinity has been associated with maintaining normal brain functions. Previously, epigenetic regulation has been shown in the promoters PII and I.3 of CYP19 in adipocytes. In the present study, the methylation of PI.f in CYP19 was examined in glial cells. Treatment of the hypomethylating agent 5-aza-2′deoxycytidine increased CYP19 mRNA species in U87 MG cells while little changes were observed in the other glia cell lines. As PI.f is also chiefly used in T98G cells with high expression of CYP19, the methylation statuses of the promoter in these two cell models were compared. Our results showed that treating U87 MG cells with 10 μM 5-aza-2′deoxycytidine significantly induced a ∼10-fold increase in CYP19 transcription and ∼80% increase in aromatase activity. In contrast, the same treatment did not change either endpoint in T98G cells. Further investigation illustrated the CpGs in PI.f were differentially methylated in the two cell lines; 63% and 37% of the 14 CpG sites were methylated in U87 MG and T98G cells respectively. In conclusion, this study illustrated that the brain-specific PI.f derived CYP19 expression can be regulated by DNA methylation.



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The prevalence of sexual aggression in Turkey: A systematic review

Publication date: Available online 27 May 2017
Source:Aggression and Violent Behavior
Author(s): Isabell Schuster, Barbara Krahé
Although sexual aggression is recognized as a serious problem worldwide, evidence on the prevalence and impact of sexual aggression is based predominantly on studies from Western countries with a Christian or non-religious majority. Little evidence is available from non-Western countries, especially from Muslim societies. The purpose of the present article was to provide a first systematic review of the studies examining the prevalence of sexual aggression in Turkey, including both victimization and perpetration reports from women and men. Additionally, differences in prevalence rates depending on relationship constellations and characteristics of victims and perpetrators were reviewed. By a two-stage literature search, 56 studies were identified for inclusion. All studies examined sexual aggression victimization of women, only four studies included sexual victimization of men. Data on sexual aggression perpetration were extremely limited, with only two studies providing prevalence rates. Prevalence rates of sexual victimization were found to vary greatly, which may be attributed to a lack of methodological and conceptual consistency across studies. Likewise, no consistent picture was revealed for victims' or perpetrators' sociodemographic or situational characteristics associated with differences in prevalence rates. We discuss reasons for the variability in prevalence rates and outline recommendations for future research.



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