Miniature transposable sequences are frequently mobilized in the bacterial plant pathogen Pseudomonas syringae pv. phaseolicola

Mobile genetic elements are widespread in Pseudomonas syringae, and often associate with virulence genes. Genome reannotation of the model bean pathogen P. syringae pv. phaseolicola 1448A identified seventeen types of insertion sequences and two miniature inverted-repeat transposable elements (MITEs) with a biased distribution, representing 2.8% of the chromosome, 25.8% of the 132-kb virulence plasmid and 2.7% of the 52-kb plasmid. Employing an entrapment vector containing sacB, we estimated that transposition frequency oscillated between 2.661025 and 1.161026, depending on the clone, although it was stable for each clone after consecutive transfers in culture media. Transposition frequency was similar for bacteria grown in rich or minimal media, and from cells recovered from compatible and incompatible plant hosts, indicating that growth conditions do not influence transposition in strain 1448A. Most of the entrapped insertions contained a full-length IS801 element, with the remaining insertions corresponding to sequences smaller than any transposable element identified in strain 1448A, and collectively identified as miniature sequences. From these, fragments of 229, 360 and 679-nt of the right end of IS801 ended in a consensus tetranucleotide and likely resulted from one-ended transposition of IS801. An average 0.7% of the insertions analyzed consisted of IS801 carrying a fragment of variable size from gene PSPPH_0008/PSPPH_0017, showing that IS801 can mobilize DNA in vivo. Retrospective analysis of complete plasmids and genomes of P. syringae suggests, however, that most fragments of IS801 are likely the result of reorganizations rather than one-ended transpositions, and that this element might preferentially contribute to genome flexibility by generating homologous regions of recombination. A further miniature sequence previously found to affect host range specificity and virulence, designated MITEPsy1 (100-nt), represented an average 2.4% of the total number of insertions entrapped in sacB, demonstrating for the first time the mobilization of a MITE in bacteria

High-fat diet alters stress behavior, inflammatory parameters and gut microbiota in Tg APP mice in a sex-specific manner

Long-term high-fat diet (HFD) consumption commonly leads to obesity, a major health concern of western societies and a risk factor for Alzheimer's disease (AD). Both conditions present glial activation and inflammation and show sex differences in their incidence, clinical manifestation, and disease course. HFD intake has an important impact on gut microbiota, the bacteria present in the gut, and microbiota dysbiosis is associated with inflammation and certain mental disorders such as anxiety. In this study, we have analyzed the effects of a prolonged (18 weeks, starting at 7 months of age) HFD on male and female mice, both wild type (WT) and TgAPP mice, a model for AD, investigating the behavioral profile, gut microbiota composition and inflammatory/phagocytosis-related gene expression in hippocampus. In the open-field test, no overt differences in motor activity were observed between male and female or WT and TgAPP mice on a low-fat diet (LFD). However, HFD induced anxiety, as judged by decreased motor activity and increased time in the margins in the open-field, and a trend towards increased immobility time in the tail suspension test, with increased defecation. Intriguingly, female TgAPP mice on HFD showed less immobility and defecation compared to female WT mice on HFD. HFD induced dysbiosis of gut microbiota, resulting in reduced microbiota diversity and abundance compared with LFD fed mice, with some significant differences due to sex and little effect of genotype. Gene expression of pro-inflammatory/phagocytic markers in the hippocampus were not different between male and female WT mice, and in TgAPP mice of both sexes, some cytokines (IL-6 and IFN¿) were higher than in WT mice on LFD, more so in female TgAPP (IL-6). HFD induced few alterations in mRNA expression of inflammatory/phagocytosis-related genes in male mice, whether WT (IL-1ß, MHCII), or TgAPP (IL-6). However, in female TgAPP, altered gene expression returned towards control levels following prolonged HFD (IL-6, IL-12ß, TNF¿, CD36, IRAK4, PYRY6). In summary, we demonstrate that HFD induces anxiogenic symptoms, marked alterations in gut microbiota, and increased expression of inflammatory genes, except for female TgAPP that appear to be resistant to the diet effects. Lifestyle interventions should be introduced to prevent AD onset or exacerbation by reducing inflammation and its associated symptoms; however, our results suggest that the eventual goal of developing prevention and treatment strategies should take sex into consideration.This work was supported by Ministerio de Economía, Industria y Competitividad (MINECO), Grant Numbers BFU2014-51836-C2-1-R to LMGS and MAA, BFU2014-51836-C2-2-R and BFU2017-82565-C21-R2 to JAC; Madrid Council S2010/BMD-2349 to MLC; Centre for Biomedical Network Research for Physiopathology of Obesity and Nutrition (CIBEROBN) to JAC, Centre for Biomedical Network Research for Frailty and Healthy Ageing (CIBERFES) to LMGS and MAA, and Centre for Biomedical Network Research for Neurodegenerative Diseases (CIBERNED) to MLC. AC-C was granted with a FPI fellowship by the MINECO (BES-2015-072980)

Physiological sex differences in microglia and their relevance in neurological disorders

Microglia are the resident immune cells in the brain and maintain homeostasis and functionality of this tissue. These cells are key producers of immune mediators, such as cytokines and chemokines, are critical for normal brain development, and affect neurogenesis, axonal migration, synapse formation and function, and programmed cell death, among others. Sex differences exist in many of these processes throughout brain development up to adulthood and the aged brain. In the last few years, sex differences in microglia responses, brain colonization, and number and morphology within the developing brain have drawn the attention of researchers as a potential explanation to the sex differences in the brain and due to their potential relevance in the incidence, prevalence, and outcome of many neurological disorders. In this review, we summarize the sex differences of microglial cell functions and their potential relevance in physiological as well as pathological conditions in the brain

Aging and sex: Impact on microglia phagocytosis

Microglia dysfunction and activation are important hallmarks of the aging brain and are concomitant with age-related neurodegeneration and cognitive decline. Age-associated changes in microglia migration and phagocytic capacity result in maladaptive responses, chronic neuroinflammation, and worsened outcomes in neurodegenerative disorders. Given the sex bias in the incidence, prevalence, and therapy response of most neurological disorders, we have here examined whether the phagocytic activity of aged microglia is different in males and females. With this aim, the phagocytosis activity of male and female cells was compared in an in vitro aged microglia model and in microglia isolated from adult (5-month-old) or aged (18-month-old) mice. In both models, the phagocytosis of neural debris increased with aging in male and female cells and was higher in aged female microglia than in aged male cells. However, female aged microglia lost its ability to adapt its phagocytic activity to inflammatory conditions. These findings suggest that microglia phagocytosis of neural debris may represent a previously unexplored neuroprotective characteristic of aged microglia that may contribute to the generation of sex differences in the manifestation of neurodegenerative diseases.The study was supported by a grant from Agencia Estatal de Investigación (AEI), co-funded by Fondo Europeo de Desarrollo Regional (FEDER): BFU2017-82754-R and by CIBERFES

Expected And Experienced Principal Behaviours Within Target Theory

Araştırmanın amacı motivasyon kuramlarından hedef belirleme kuramı çerçevesinde okul yöneticisinden beklenen davranışlar ile gerçekleştirdikleri davranışları öğretmenlerin görüşlerine dayalı olarak belirleyebilmektir. Bu çalışmada nitel araştırma yöntemi kullanılmıştır. Çalışma grubunun belirlenmesinde amaçlı örnekleme yöntemi ve buna bağlı olarak maksimum çeşitlilik ve ölçüt örnekleme teknikleri kullanılmıştır. 2013-2014 eğitim öğretim yılında Sinop ve Düzce illerinde yüksek lisans yapan veya yüksek lisans mezunu 42 öğretmen katılımcı olarak belirlenmiştir. Araştırmada, araştırmacılar tarafından geliştirilmiş yarı yapılandırılmış görüşme formu kullanılmıştır. Verilerin analizinde nitel veri çözümleme tekniği olarak içerik analiz kullanılmıştır. Katılımcı öğretmenlerin çoğu, zor hedeflerin kolay hedeflere göre daha yüksek performans sağlayacağını ve zor hedefler için yüksek performans göstereceklerini ifade etmişlerdir. Araştırmanın bir diğer sonucuna göre katılımcılardan belirgin hedeflerin daha doğru olacağını ifade edenlerin sayısı belirsiz hedeflerin doğru olacağını söyleyenlerin yaklaşık olarak iki katıdır. Aynı zamanda, yöneticilerin zor hedef belirlediğinde bunları gerçekleştirmek için öğretmenler daha fazla gayret göstermektedirler. Hedeflere ulaşılıp ulaşılmadığına dair yöneticilerin geri bildirim yaparken sadece olumsuz değil olumlu ve öğretmeni motive edici geri bildirim de yapması gerektiğini, hedeflerin değerlendirilmesinde yöneticinin de yapıcı değerlendirmeleriyle öğretmenin yaptıklarını takdir etmesi gerektiğini ifade etmişlerdir. Hedeflere ulaşılıp ulaşılmadığına dair yöneticiden geri bildirip alınıp alınmadığı ve buna gerek olup olmadığına dair sorulan soruya katılımcıların yarısı dönüt aldıklarını, üçte biri dönüt alamadıklarını ancak buna gerek olduğunu ifade etmişlerdir. Katılımcıların sadece çok az bir kısmı geri bildirime gerek olmadığını belirtmişlerdir. Elde edilen araştırma sonuçları hedef kuramı teorisi ilkeleri ile paralellik göstermektedir.The aim of the research is to determine the expected behaviours and currently experienced behaviours of the principals within the scope of target theory with the help of teachers' opinions. Qualitative research method, which enables detailed examination of a single case or several cases, was used in the research. Purposeful sampling method and accordingly maximum variation and criterion sampling techniques were conducted in determining the study group. The determination of the study group Ondokuz Mayıs üniversitesi, Eğitim Bilimleri Fakültesi, Eğitim Bilimleri Bölümü, [email protected] ***Düzce üniversitesi, Eğitim Bilimleri Fakültesi, Eğitim Bilimleri Bölümü, suleywas based on voluntariness of the teachers. The study group consists of 42 teachers who either have been maintaining a master's degree program or have a master's degrree in Sinop and Düzce in 2013-2014 academic year. A semi-structured interview form developed by the researchers was used and content analysis was conducted as a qualitative data analysis technique in data analysis. The best part of the participant teachers stated that challenging targets would provide higher performances in comparison with the easier ones and that they would perform better for the challenging targets. Also the number of participants supporting the significant targets are two times more than the number of participants claiming that unspecified targets would be better. The research results demonstrate that when the principals set challenging targets, teachers spread more effort to accomplish them. The teachers state that principals should give positive and motivating feedback and that they should appreciate the teachers with constructive evaluations. The participants were asked whether they have received feedback on the targets. Half of them remarked that they have received feedback, while one-third of them stated that they have not received feedback and that they need to receive. Only a few of the participants regarded feedback as unnecessary. These research results are parallel with the principles of the theory

Unveiling the Role of the Tumor Microenvironment in the Treatment of Follicular Lymphoma

Follicular lymphomas (FL) are neoplasms that resemble normal germinal center (GC) B-cells. Normal GC and neoplastic follicles contain non-neoplastic cells such as T-cells, follicular dendritic cells, cancer associated fibroblasts, and macrophages, which define the tumor microenvironment (TME), which itself is an essential factor in tumor cell survival. The main characteristics of the TME in FL are an increased number of follicular regulatory T-cells (Treg) and follicular helper T-cells (Tfh), M2-polarization of macrophages, and the development of a nodular network by stromal cells that creates a suitable niche for tumor growth. All of them play important roles in tumor angiogenesis, inhibition of apoptosis, and immune evasion, which are key factors in tumor progression and transformation risk. Based on these findings, novel therapies have been developed to target specific mutations present in the TME cells, restore immune suppression, and modulate TME

Estrogenic Regulation of Glia and Neuroinflammation

Estrogens are rapid and potent facilitators of synaptic plasticity in the adult brain; however, the steps that link estrogens to factors that regulate synaptic strength remain unclear. The present chapter will first review the acute effects of 17β‎-estradiol on synaptic transmission and long-term potentiation (LTP). It will then describe a synaptic model used to study the substrates of LTP and provide evidence for the ability of estradiol to rapidly engage a selective actin signaling cascade associated with the consolidation of LTP. Finally, it will be shown that chronic reductions in estradiol levels disrupt LTP and actin dynamics but can be reversed by acute infusions of the hormone. It is concluded here that estradiol can promote learning-related plasticity by modifying the synaptic cytoskeleton.Authors acknowledge economic support from Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERFES), Spain

Estrogenic regulation of neuroprotective and neuroinflammatory mechanisms: implications for depression and cognition

Glial cells, such as astrocytes and microglia, contribute to maintain tissue homeostasis in the brain and are involved in the control of neuronal function, synaptic plasticity, and neuroinflammation. In the aged brain and under neurodegenerative conditions, microglial cells acquire a senescent reactive phenotype, which involves a dysregulated inflammatory response that affects the normal function and metabolism of neurons and other cell types, including astrocytes. The impaired function of astrocytes and microglia in the aged brain increases neuroinflammation, which is associated with depressive disorders and cognitive deficits. Estradiol, from gonadal origin or locally produced in the brain, exerts anti-inflammatory actions in the central nervous system, regulating the reactive phenotype of astrocytes and microglia. In addition, estrogen receptor signaling exerts direct neuroprotective actions on neurons and interacts with the signaling of other neuroprotective and anti-inflammatory factors in the brain. These actions of estradiol and estrogen receptors contribute to maintain a proper neuronal information processing, promoting cognitive function and preventing affective disorders. The effects of estradiol are imitated by synthetic estrogenic compounds, such as some selective estrogen receptor modulators and tibolone.Authors acknowledge the support from Ministerio de Economía, Industria y Competitividad (MINECO), Spain (grant number BFU2017-82754-R); Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES); Instituto de Salud Carlos III, Madrid, Spain; and Fondos FEDER

Curso CSIC: Una visión actualizada de la neurociencia desde el Instituto Cajal

El impresionante avance de la investigación en Neurociencia del último siglo ha arrojado luz acerca de la estructura y funcionamiento del sistema nervioso central. La Neurociencia ha experimentado increíbles avances que han permitido no sólo ampliar nuestro conocimiento acerca de cómo funcionan procesos mentales como la memoria o el aprendizaje, sino también diseñar terapias específicas para enfermedades neurodegenerativas o desarrollar tecnologías de elevado impacto social como es el caso de la inteligencia artificial. En este curso, se hará un recorrido general sobre la historia de la Neurociencia, incidiendo en la estructura macroscópica y microscópica del cerebro y médula espinal, así como patologías asociadas al desarrollo y en el adulto. También se comentarán los últimos datos acerca de disciplinas asociadas como la inteligencia artificial y los trastornos de la conducta alimentaria, así como campos emergentes como la Neuroeducación. Finalmente, se plantearán las técnicas y modelos disponibles para el estudio de la Neurociencia, y se propondrán fuentes para la búsqueda de noticias y recursos científicos fiables