scholarly journals TREM2 impacts brain microglia, oligodendrocytes and endothelial co-expression modules revealing genes and pathways important in Alzheimer s disease

2021 ◽  
Author(s):  
Guillermo Carbajosa ◽  
Karim Malki ◽  
Nathan Lawless ◽  
Hong Wang ◽  
John W Ryder ◽  
...  
Keyword(s):  
Negative Impact ◽  
Cell Types ◽  
Antigenic Peptides ◽  
Receptor Function ◽  
Fcγ Receptor ◽  
Treatment Development ◽  
Endothelial Genes ◽  
Effector Pathways ◽  
Lipid Sensor ◽  
The Impact

A microglia response to pathogenic signals in diseases such as Alzheimer s disease (AD) has long been recognised, but recent genetic findings have cemented their direct causal contribution to AD and thus the potential to target them or their effector pathways as a possible treatment strategy. TREM2 is a highly penetrant microglia risk gene for AD, which appears central to the coordination of the damage response by microglia in AD. Its absence has a negative impact on Tau and amyloid symptoms and pathologies. Full knowledge of its pathway and relationships with other brain cells in AD has not been fully characterised, but will be essential to fully evaluate the impact of manipulating this pathway for treatment development and to establish the best targets for achieving this. We used whole genome RNA sequencing of hippocampus and cortical brain samples from control, AD, and AD TREM2 risk carriers to identify TREM2-dependent genes driving changes in pathways, processes and cell types in AD. Through highly influential intra and intermodular hub genes and overall changes in the levels of gene expression, TREM2-DAP12 was found to strongly influence a number of other microglia, oligodendrocyte and endothelial genes, notably those involved in complement and Fcγ receptor function, microglia-associated ribosomal genes and oligodendrocyte genes, particularly proteosomal subunits. These strong TREM2 centred co-expression relationships were significantly disrupted in AD cases with a TREM2 risk variant, revealing for the first time genes and pathways directly impacted by TREM2 in the brains of AD patients. Consistent with its function as a lipid sensor, our data supports a role for TREM2 in mediating oligodendrocyte and/or myelin clearance in AD which may be essential not only for preserving healthy tissue homeostasis but may also serve to minimise the persistence of antigenic peptides and lipids which may lead to detrimental pro-inflammatory sequelae. Further work should expand our knowledge of TREM2 on complement and Fcγ receptor function and its impact on oligodendcrotye and myelin integrity and further evaluate the genes and pathways we have identified as possible treatment targets for AD.

scholarly journals TMIC-53. IMPACT OF HFE EXPRESSION AND SEX ON THE TUMOR IMMUNE MICROENVIRONMENT IN GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi259-vi259
Author(s):  
Darya Nesterova ◽  
Sang Lee ◽  
Brad Zacharia ◽  
Justin Lathia ◽  
Joshua Rubin ◽  
...  
Keyword(s):  
Stromal Cell ◽  
Immune Cell ◽  
Negative Impact ◽  
Methylation Status ◽  
Cell Types ◽  
Cell Infiltration ◽  
M2 Macrophage ◽  
Mgmt Methylation ◽  
Expression Levels ◽  
The Impact

Abstract Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Despite aggressive treatment, the median survival for patients with GBM remains approximately 1 year. Recent evidence demonstrates GBM is a sexually dimorphic disease, and that females have greater overall survival. We previously showed expression levels of HFE, an iron-regulating gene, significantly impacts survival in GBM. Moreover, this effect is sex-specific: females with low HFE expressing tumors have significantly longer survival than males with similar HFE expression. Moreover, HFE expression and survival appeared to correlate with markers of immune activity within the tumors. To further explore the impact of HFE expression on the immune infiltration of GBM, we utilized available TCGA GBM data for analysis by EstimateMe and DeconvuluteMe. These platforms utilize expression data to estimate the magnitude and cellular composition of immune cell infiltrates in tumors, respectively. We sought to correlate these computational measures with HFE expression levels and survival. We confirmed that immune and stromal cell infiltration of tumors is negatively correlated to survival. Consistent with our findings that high HFE levels have a negative impact on survival, high HFE expressing tumors possessed higher levels of both immune and stromal cell infiltration. Additionally, sex of the patient, but not MGMT methylation status, was significantly correlated with immune and stromal infiltration, with males displaying higher levels of infiltration. High HFE tumors were composed of greater numbers of all immune cell types than low HFE tumors. In both HFE groups, monocytes and macrophages comprised the greatest fraction of cells. At low HFE and positive MGMT methylation (where we previously noted the greatest survival differences), we find females have lower monocyte and M2 macrophage markers compared to males with similar features. Collectively, these data suggest that an HFE-immune cell infiltrate axis contributes to sex differences in GBM survival.

scholarly journals Impact of ursodeoxycholic acid on a CCK1R cholesterol-binding site may contribute to its positive effects in digestive function

2015 ◽  
Vol 309 (5) ◽  
pp. G377-G386 ◽  
Author(s):  
Aditya J. Desai ◽  
Maoqing Dong ◽  
Kaleeckal G. Harikumar ◽  
Laurence J. Miller
Keyword(s):  
Bile Acid ◽  
Ursodeoxycholic Acid ◽  
Bile Acids ◽  
Chenodeoxycholic Acid ◽  
Negative Impact ◽  
Gallstone Formation ◽  
Membrane Cholesterol ◽  
Receptor Function ◽  
Positive Effects ◽  
The Impact

Dysfunction of the type 1 cholecystokinin (CCK) receptor (CCK1R) as a result of increased gallbladder muscularis membrane cholesterol has been implicated in the pathogenesis of cholesterol gallstones. Administration of ursodeoxycholic acid, which is structurally related to cholesterol, has been shown to have beneficial effects on gallstone formation. Our aims were to explore the possible direct effects and mechanism of action of bile acids on CCK receptor function. We studied the effects of structurally related hydrophobic chenodeoxycholic acid and hydrophilic ursodeoxycholic acid in vitro on CCK receptor function in the setting of normal and elevated membrane cholesterol. We also examined their effects on a cholesterol-insensitive CCK1R mutant (Y140A) disrupting a key site of cholesterol action. The results show that, similar to the impact of cholesterol on CCK receptors, bile acid effects were limited to CCK1R, with no effects on CCK2R. Chenodeoxycholic acid had a negative impact on CCK1R function, while ursodeoxycholic acid had no effect on CCK1R function in normal membranes but was protective against the negative impact of elevated cholesterol on this receptor. The cholesterol-insensitive CCK1R mutant Y140A was resistant to effects of both bile acids. These data suggest that bile acids compete with the action of cholesterol on CCK1R, probably by interacting at the same site, although the conformational impact of each bile acid appears to be different, with ursodeoxycholic acid capable of correcting the abnormal conformation of CCK1R in a high-cholesterol environment. This mechanism may contribute to the beneficial effect of ursodeoxycholic acid in reducing cholesterol gallstone formation.

Urbanization of fauna on the example of marsh frog (Pelophylax ridibundus)

2015 ◽  
Vol 26 (3-4) ◽  
pp. 116-123
Author(s):  
A. P. Korzh ◽  
T. V. Zahovalko
Keyword(s):  
Urban Areas ◽  
Cognitive Modeling ◽  
Negative Impact ◽  
Natural Populations ◽  
Cellular Level ◽  
Anthropogenic Factors ◽  
Migration Routes ◽  
Corrective Effect ◽  
The Impact ◽  
The City

Recently, the number of published works devoted to the processes of synanthropization of fauna, is growing like an avalanche, which indicates the extreme urgency of this theme. In our view, the process of forming devices to coexist with human and the results of his life reflects the general tandency of the modern nature evolution. Urbanization is characteristic for such a specific group of animals like amphibians, the evidence of which are numerous literature data. Many researchers use this group to assess the bioindicative quality of the environment. For this aim a variety of indicators are used: from the cellular level of life of organization up to the species composition of the group in different territories. At the same time, the interpretation of the results is not always comparable for different areas and often have significantly different interpretations by experts. Urban environment, primarily due to the contamination is extremely aggressive to amphibians. As a consequence, the urban populations of amphibians may be a change in the demographic structure, affecting the reproductive ability of the population, the disappearance of the most sensitive species or individuals, resizing animals, the appearance of abnormalities in the development, etc. At the same time play an important amphibians in the ecosystems of cities, and some species in these conditions even feel relatively comfortable. Therefore, it is interesting to understand the mechanisms of self-sustaining populations of amphibians in urban environments. To assess the impact of natural and anthropogenic factors on the development of amphibian populations were used cognitive modeling using the program Vensim PLE. Cognitive map of the model for urban and suburban habitat conditions were the same. The differences concerned the strength of connections between individual factors (migration, fertility, pollution) and their orientation. In general, factors like pollution, parasites, predators had negative impact on the population, reducing its number. The birth rate, food and migration contributed to raising number of individuals. Some of the factors affected on the strength to of each other as well: the majority of the factors affected the structure of the population, had an influence on the fertility. Thanks to it the model reflects the additive effect of complex of factors on the subsequent status of the population. Proposed and analyzed four scenarios differing strength and duration of exposure. In the first scenario, a one-time contamination occurs and not subsequently repeated. The second and third scenario assumes half board contamination, 1 year (2 scenario) and two years (scenario 3). In the fourth scenario, the pollution affected the population of amphibians constantly. In accordance with the results of simulation, much weaker than the natural populations respond to pollution - have them as an intensive population growth and its disappearance at constant pollution is slow. Changes to other parameters of the model showed that this pollution is the decisive factor -only the constant action leads to a lethal outcome for the populations. All other components of the model have a corrective effect on the population dynamics, without changing its underlying trand. In urban areas due to the heavy impact of pollution maintaining the population is only possible thanks to the migration process – the constant replenishment of diminishing micropopulations of natural reserves. This confirms the assumption that the form of existence metapopulations lake frog in the city. In order to maintain the number of amphibians in urban areas at a high level it is necessary to maintain existing migration routes and the creation of new ones. Insular nature of the placement of suitable habitats in urban areas causes the metapopulation structure of the types of urbanists. Therefore, the process of urbanization is much easier for those species whicht are capable of migration in conditions of city. In the initial stages of settling the city micropopulationis formed by selective mortality of the most susceptible individuals to adverse effects. In future, maintaining the categories of individuals is provided mainly due to migration processes metapopulisation form of the species of existence is supported). It should be noted that the changes in the previous levels are always saved in future. In the case of reorganizations of individuals we of morphology can assume the existence of extremely adverse environmental conditions that threaten the extinction of the micropopulations. 

Modernisation of Higher Education – Willful Action or Wishful Thinking? The Case of Bulgaria

2020 ◽  
Vol 8 (3) ◽  
pp. 3-17
Author(s):  
Elena Blagoeva
Keyword(s):  
Higher Education ◽  
Economic Crisis ◽  
Negative Impact ◽  
National Level ◽  
Sustainable Growth ◽  
Research Approach ◽  
Case Study Methodology ◽  
The Impact ◽  
The Eu

The impact of the last global economic crisis (2008) on the European economy put a strain on higher education (HE), yet it also pushed the sector towards intensive reforms and improvements. This paper focuses on the “Strategy for the Development of Higher Education in the Republic of Bulgaria 2014-2020”. With a case study methodology, we explore the strategic endeavours of the Bulgarian government to comply with the European directions and to secure sustainable growth for the HE sector. Our research question is ‘How capable is the Bulgarian HE Strategy to overcome the economic and systemic restraints of Bulgarian higher education?’. Because the development of strategies for HE within the EU is highly contextual, a single qualitative case study was chosen as the research approach. HE institutions are not ivory towers, but subjects to a variety of external and internal forces. Within the EU, this is obviated by the fact that Universities obtain their funds from institutions such as governments, students and their families, donors, as well as EU-level programmes. Therefore, to explore how these pressures interact to affect strategic action on national level, the case method is well suited as it enabled us to study the phenomena thoroughly and deeply. The paper suggests the actions proposed within the Strategy have the potential to overcome the delay, the regional isolation and the negative impact of the economic crisis on the country. Nevertheless, the key elements on which the success or failure of this Strategy hinges are the control mechanisms and the approach to implementation. Shortcomings in these two aspects of strategic actions in HE seem to mark the difference between gaining long-term benefits and merely saving face in front of international institutions.

Morphological features of endo- and myometrium in patients with uterine leiomyoma and infertility

2020 ◽  
pp. 33-37
Author(s):  
M.A. Flaksenberg ◽  
◽  
Keyword(s):  
Uterine Leiomyoma ◽  
Negative Impact ◽  
Reproductive Function ◽  
Cell Types ◽  
Underlying Disease ◽  
Reproductive Organs ◽  
Pathological Process ◽  
Simple Type ◽  
Morphological Examination ◽  
Blastocyst Implantation

The objective: determination of morphofunctional features of leiomatous nodes and endometrium in women with uterine leiomyoma and infertility to restore reproductive function and prevent recurrence of the underlying disease. Materials and methods. In order to restore reproductive function and prevent recurrence of the underlying disease, morphofunctional features of leiomatous nodes and endometrium in women with uterine leiomyoma and infertility were determined. Thirty samples of leiomyomatous nodes and endometrium were examined, among which 15 were obtained from women with multiple uterine leiomyoma and infertility and 15 samples from women with uterine leiomyoma with isolated uterine leiomyoma. During the study, a general-histological method was used for staining with hematoxylin-eosin and picrofuxin by van Gizon, as well as immunohistochemical methods. Histological examination of the endometrium was performed according to conventional protocol, taking into account the day of the menstrual cycle and R.W. Noyes criteria. Results. In the morphological examination of leiomyomatous nodes in the vast majority of cases the presence of uterine leiomyomas of simple and cell types or their combination was established. In women with multiple uterine leiomyoma, simple-type leiomyoma (53.3%) was predominant, and in patients with isolated leiomyoma the signs of cellular uterine leiomyoma (66.7%) were more frequently found. In 80.0% of women with uterine leiomyoma revealed pathology of the endometrium, such as glandular and glandular-fibrous polyps, simple and complex atypical endometrial hyperplasia, which confirms the theory about the only pathogenetic mechanisms of the emergence of hyperplastic processes of female organs. In 66.7% of women with multiple leiomyomas, signs of chronic endometritis have been found, which exacerbates the pathological process and can have a negative impact on the reproductive function, such as secretory endometrial transformation and impaired blastocyst implantation, and explains a much higher percentage of infertility in the group. Conclusion. In women with impaired reproductive function, patients with uterine leiomyoma, it is necessary to conduct a study of the receptivity of the reproductive organs, namely - the endometrium and leiomatous nodes. This will make it possible to use one or another method of treatment in order to restore reproductive function and prevent recurrence of the underlying disease. Keywords: infertility, uterine leiomyoma, endometrium, receptive apparatus.

Has Aid Helped in Pakistan?

1997 ◽  
Vol 36 (4II) ◽  
pp. 947-957 ◽  
Author(s):  
Shahrukh Rafi Khan
Keyword(s):  
Economic Growth ◽  
Negative Impact ◽  
Negative Association ◽  
Causal Impact ◽  
The Impact ◽  
Over Time

This paper has a two-fold objective: first, to examine the terms on which Pakistan receives aid and whether its debt situation is sustainable, and second, to examine the impact of aid and debt on economic growth. It is found that there is little encouraging that can be said about how the terms on which Pakistan has received aid over time have changed, and its current debt situation is not sustainable. Also reported is the analysis done elsewhere which shows that aid has a negative (Granger) causal impact on GDP, and aid has a robust negative impact on economic growth after controlling for supplyside shocks. We provide various reasons for this negative association.

Green Beans Cultivation Using Mice Pets Control to Improve the Quality of Bintaro Fruit Extract

2018 ◽  
Vol 1 (1) ◽  
pp. 38
Author(s):  
Ajeng Embri Legawati ◽  
Nur Azizah ◽  
Achmad Ramadhan
Keyword(s):  
Natural Resources ◽  
Negative Impact ◽  
Green Beans ◽  
Fruit Extract ◽  
Bean Plants ◽  
Cultivation Technology ◽  
Environmental Balance ◽  
The Impact ◽  
Chemical Pesticides

Green beans cultivation technology using mice pets control has been implemented in the Gluranploso village, Benjeng Gresik. The implementation of the technology performed for 2.5 months from August to October 2017. The purpose of the implementation is aimed to reduce the dependence of farmers on the use of chemical pesticides so that the farmers are aware of the negative impact of chemical pesticides. Assessing the impact of the utilization of Bintaro fruit and fruit extracts to explore ways of making Bintaro as a natural biopesticide to overcome rat attack on green bean plants in the Gluranploso village. Pest control mice can reduce the rate of loss of the crops more effectively and efficiently. Finally, with the use of those natural resources as a biopesticide material can also maintain the environmental balance

The impact of the COVID-19 pandemic on the psychosocial condition of students in Poland and Ukraine

2020 ◽  
Author(s):  
Piotr Długosz ◽  
Yana
Keyword(s):  
Distance Learning ◽  
Negative Impact ◽  
Well Being ◽  
Survey Method ◽  
Psychosocial Condition ◽  
On Line ◽  
Line Survey ◽  
The Impact ◽  
Emotional Condition ◽  
Double Measurement

The article presents the results of research on psychosocial condition among Polish and Ukrainian students during the quarantine. The aim of the research was to verify the impact of the pandemic and its accompanying phenomena on the well-being of youth. In order to achieve this goal, the CAWI on-line survey method with double measurement was used. The first measurement carried out at the beginning of the quarantine resulted in 3659 filled out surveys in Poland and 739 in Ukraine. The second measurement conducted at the end of distance learning brought 1978 filled out surveys in Poland and 411 in Ukraine. The results of research indicate that the quarantine had a negative impact on the psychosocial condition of youth. The deterioration of emotional condition and the increase in mental disorders has been observed. Due to the pandemic and distance learning, the mental health of youth deteriorated significantly. Polish youth were negatively influenced by the pandemic to a greater extent than young Ukrainians.

TO THE QUESTION OF THE IMPACT OF CLIMATE CHANGE ON THE ECOLOGICAL STATE OF ARTIFICIAL PLANTATIONS OF PITSUNDSKAYA PINE IN THE SEASIDE AREA OF GELENDZHIK

2017 ◽  
Author(s):  
Elizaveta Derevenets ◽  
Elizaveta Derevenets
Keyword(s):  
Negative Impact ◽  
Standard Technique ◽  
Negative Influence ◽  
Exhaust Gases ◽  
The Road ◽  
Industrial Enterprises ◽  
Federal Highway ◽  
On The Road ◽  
The Impact ◽  
The City

Gelendzhik is the resort town, there aren't a lot of industrial enterprises here. The main pollutant is transport. The work purpose is the assessment of a condition of the artificial landings of a pine located along the Federal highway "Don" and landings, which is nearly the sea coast. Researches were conducted to a standard technique of the General vital state (A. S. Bogolyubov). The assessment of a condition of pines was carried out during 6 years: from 2010 to 2015. For carrying out research we used 6 experimental grounds on the Markotkhsky spine and 2 control grounds within the town. We investigated 24 trees on each platform, middle age of the trees were 30 - 40 years. Results. 1. The condition of trees in the pine forests located in immediate proximity with the Federal highway "Don" (No. 1, 2, 3) is unsatisfactory. As even weak influences of the majority of atmospheric gaseous pollutants (sulphurous gas, nitrogen oxides, etc.) give effect of a necrosis and hloroz of pine needles, the condition of pines is connected with technogenic pollution. So near the Federal highway "Don" the air environment is strongly polluted by exhaust gases. Information of 2012 confirm that negative influence of the route on Markotkh's vegetation decreases at reduction of load of the route. 2. On the sites located above on a slope (No. 4,5,6) thanks to remoteness and the wind mode intensity of influence of pollutants is lower and a condition of pines the quite satisfactory. 3. Trees on the sites located near the sea (No. 7,8) are in a good shape. Small deterioration of a state is noted in very droughty years. Conclusion. Results of six years' research show that the condition of the plantings which are in close proximity with the road worsens. It is explained by increase in intensity of the movement on the road, especially during a resort season. Gelendzhik is the city with a good ecological shape, but the damage to environment is already caused. If not to take measures, we can lose a unique part of the nature in the future, recreate it will be impossible. Measures of reduction of negative impact of exhaust gases were offered. Results of researches are transferred to ecological department of the City administration of Gelendzhik.

Corporate Social Responsibility and Earnings Management: The Moderating Role of Family Ownership

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Asif Saeed ◽  
Aijaz Mustafa Hashmi ◽  
Attiya Yasmin Javid
Keyword(s):  
Corporate Social Responsibility ◽  
Social Responsibility ◽  
Earnings Management ◽  
Family Firms ◽  
Negative Impact ◽  
Stock Exchange ◽  
Least Square ◽  
Family Ownership ◽  
Corporate Social ◽  
The Impact

This study aims to explore the impact of family ownership on the relationship among corporate social responsibility (CSR) and earning management (EM) in Pakistan. Data is collected from nonfinancial listed firms on Pakistan Stock Exchange (PSE) for the period 2009-2017. Our results of pooled ordinary least square regression indicate that CSR has significant negative impact on EM. Furthermore, results also indicate that association between CSR and EM is moderated by family ownership. Family firms which perform CSR activities are less involved in EM as compare to nonfamily firms perform CSR activities. This variation in behavior of EM in family and non-family firms can possibly be explained by socioemotional wealth theory. Keywords: Corporate Social Responsibility, Earnings Management, Family Ownership

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