Clonally focused public and private T cells in resected brain tissue from surgeries to treat children with intractble seizures.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE168741 | GEO | 2021/03/12
REPOSITORIES: GEO
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Project description:Using a targeted transcriptomics approach, we have analyzed resected brain tissue from a cohort of 53 pediatric epilepsy surgery cases, and have found that there is a spectrum of involvement of both the innate and adaptive immune systems as evidenced by the differential expression of immune-specific genes in the affected brain tissue. The specimens with the highest expression of immune-specific genes were from two Rasmussen encephalitis cases, which is known to be a neuro-immunological disease, but also from tuberous sclerosis complex (TSC), focal cortical dysplasia, and hemimegalencephaly surgery cases. We obtained T cell receptor (TCR) Vβ chain sequence data from brain tissue and blood from patients with the highest levels of T cell transcripts. The clonality indices and the frequency of the top 50 Vβ clonotypes indicated that T cells in the brain were clonally restricted. The top 50 Vβ clonotypes comprised both public and private (patient specific) clonotypes, and the TCR Vβ chain third complementarity region (CDR3) of the most abundant public Vβ clonotype in each brain sample was strikingly similar to a CDR3 that recognizes an immunodominant epitope in either human cytomegalovirus or Epstein Barr virus, or influenza virus A. We found that the frequency of 14 of the top 50 brain Vβ clonotypes from a TSC surgery case had significantly increased in brain tissue removed to control recurrent seizures 11 months after the first surgery. Conversely, we found that the frequency in the blood of 18 of the top 50 brain clonotypes from a second TSC patient, who was seizure free, had significantly decreased 5 months after surgery indicating that T cell clones found in the brain had contracted in the periphery after removal of the brain area associated with seizure activity and inflammation. However, the frequency of a public and a private clonotype significantly increased in the brain after seizures recurred and the patient underwent a second surgery. Combined single cell gene expression and TCR sequencing of brain-infiltrating leukocytes from the second surgery showed that the two clones were CD8 effector T cells, indicating that they are likely to be pathologically relevant.
| S-EPMC8056262 | biostudies-literature
Project description:Clonally focused public and private T cells in resected brain tissue from surgeries to treat children with intractble seizures.
| PRJNA713799 | ENA
Project description:Cortical tubers in patients with tuberous sclerosis complex (TSC) are associated with cognitive disability and intractable epilepsy. While these developmental malformations are believed to result from the effects of TSC1 or TSC2 Gene mutations, the molecular mechanisms leading to tuber formation during brain development as well as the onset of seizures remain largely unknown. We used the Affymetrix Gene Chip platform as a genome-wide strategy to define the Gene expression profile of cortical tubers resected during epilepsy surgery compared to histologically normal perituberal tissue (adjacent to the cortical tuber) from the same patients or autopsy control tissue.
2010-02-02 | GSE16969 | GEO
Project description:Global gene expression signatures was analysed through microarray expression profiling as a discovery platform to identify up and down regulated ESTs that represent genes involved in metabolic pathways in the leaf, fibrous root and storage root (tuber forming root) of sweetpotato (Ipomoea batatas) as affcted by high temperature stress (40oC) compared to ambient temperature (30oC). Also Global gene expression signatures was analysed by the same procedure to explore up and down regulated ESTs in tuberous root of sweet potato in comparison with fibrous root of Ipomoea cornea and identify unique ESTs that represent genes involved in tuber formation in sweet potato.
2015-10-01 | GSE51862 | GEO
Project description:In many Western societies there are rising concerns about increasing polarization in public debate. However, statistics on private attitudes paint a different picture: the average attitudes in societies are more moderate and remain rather stable over time. The present paper presents an agent-based model of how such discrepancies between public opinion and private attitudes develop at the scale of micro-societies. Based on social psychological theorizing, the model distinguishes between two types of agents: a) those seeking to gain or maintain a good reputation and status, and b) those seeking to promote group harmony by reaching consensus. We characterized these different types of agents by different decision rules for either voicing their opinion or remaining silent, based on the behavior of their proximal network. Results of the model simulations show that even when the private attitudes of the agents are held constant, publicly expressed opinions can oscillate and (depending on the reputational concerns of individual actors) situations can occur in which minorities as well as majorities are silenced. We conclude that the macro-level consequences of micro-level decisions to either voice an opinion or remain silent provide a foundation for better understanding how public opinions are shaped. Moreover, we discuss the conditions under which public opinion could be considered a good representation of private attitudes in a society.
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Project description:BackgroundPrivacy protecting is an important issue in medical informatics and differential privacy is a state-of-the-art framework for data privacy research. Differential privacy offers provable privacy against attackers who have auxiliary information, and can be applied to data mining models (for example, logistic regression). However, differentially private methods sometimes introduce too much noise and make outputs less useful. Given available public data in medical research (e.g. from patients who sign open-consent agreements), we can design algorithms that use both public and private data sets to decrease the amount of noise that is introduced.MethodologyIn this paper, we modify the update step in Newton-Raphson method to propose a differentially private distributed logistic regression model based on both public and private data.Experiments and resultsWe try our algorithm on three different data sets, and show its advantage over: (1) a logistic regression model based solely on public data, and (2) a differentially private distributed logistic regression model based on private data under various scenarios.ConclusionLogistic regression models built with our new algorithm based on both private and public datasets demonstrate better utility than models that trained on private or public datasets alone without sacrificing the rigorous privacy guarantee.
| S-EPMC4101668 | biostudies-literature
Project description:Rasmussen encephalitis (RE) is a rare pediatric neuroinflammatory disease characterized by intractable seizures and unilateral brain atrophy. T cell infiltrates in affected brain tissue and the presence of circulating autoantibodies in some RE patients have indicated that RE may be an autoimmune disease. The strongest genetic links to autoimmunity reside in the MHC locus, therefore, we determined the human leukocyte antigen (HLA) class I and class II alleles carried by a cohort of 24 RE surgery cases by targeted in-depth genomic sequencing. Compared with a reference population the allelic frequency of three alleles, DQA1*04:01:01, DQB1*04:02:01, and HLA-C*07:02:01:01 indicated that they might confer susceptibility to the disease. It has been reported that HLA-C*07:02 is a risk factor for Graves disease. Further, eight patients in the study cohort carried HLA-A*03:01:01:01, which has been linked to susceptibility to multiple sclerosis. Four patients carried a combination of three HLA class II alleles that has been linked to type 1 diabetes (DQA1*05:01:01:01~DQB1*02:01:01~DRB1*03:01:01:01), and five patients carried a combination of HLA class II alleles that has been linked to the risk of contracting multiple sclerosis (DQA1*01:02:01:01, DQB1*06:02:01, DRB1*15:01:01:01). We also analyzed the diversity of αβ T cells in brain and blood specimens from 14 of these RE surgery cases by sequencing the third complementarity regions (CDR3s) of rearranged T cell receptor β genes. A total of 31 unique CDR3 sequences accounted for the top 5% of all CDR3 sequences in the 14 brain specimens. Thirteen of these sequences were found in sequencing data from healthy blood donors; the remaining 18 sequences were patient specific. These observations provide evidence for the clonal expansion of public and private T cells in the brain, which might be influenced by the RE patient's HLA haplotype.
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Project description:Stakeholder engagement is generally considered one of the most pertinent factors impacting project outcomes. However, there is lacking empirical evidence documenting patterns of stakeholder engagement and their potential differences between public, private and public-private partnership (PPP) projects. This study leverages social network research methods to capture and quantitively compare these engagement structures. Stakeholder network data were collected by an online questionnaire from 17 public, 30 private and 9 PPP projects. A series of network-based analyses were subsequently applied to the data at both the level of individual project stakeholders and entire project stakeholder ecologies. A statistically significant difference (p<0.05) exists among the network-level measures of network size, edge number, density and betweenness centralization across the three project types. Among these four network measures, the density varies significantly (p<0.05) between 'within budget' and cost overrun projects for the private and PPP projects. The top-5 stakeholder lists with respect to three node-level centrality values reveal distinctive differences across the three project types. To further interpret the data, exponential random graph models were also applied to determine the most statistically prevalent network motifs within each type of project. Again, statistically significant differences were found across these three project types. The findings consistently point to structural differences in patterns of stakeholder engagement across the public and private domain and illustrate the applicability of network data and analytical techniques to monitoring and managing complex webs of relationships among actors who affect and are affected by diverse types of projects.
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Project description:During the past decades, the traditional state monopoly in urban water management has been debated heavily, resulting in different forms and degrees of private sector involvement across the globe. Since the 1990s, China has also started experiments with new modes of urban water service management and governance in which the private sector is involved. It is premature to conclude whether the various forms of private sector involvement will successfully overcome the major problems (capital shortage, inefficient operation, and service quality) in China's water sector. But at the same time, private sector involvement in water provisioning and waste water treatments seems to have become mainstream in transitional China.
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Project description:Public health enjoyed a number of successes over the twentieth century. However, public health agencies have arguably been ill equipped to sustain these successes and address the complex threats we face today, including morbidity and mortality associated with persistent chronic diseases and emerging infectious diseases, in the context of flat funding and new and changing health care legislation. Transformational leaders, who are not afraid of taking risks to develop innovative approaches to combat present-day threats, are needed within public health agencies. We propose the Public Health Innovation Model (PHIM) as a tool for public health leaders who wish to integrate innovation into public health practice. This model merges traditional public health program planning models with innovation principles adapted from the private sector, including design thinking, seeking funding from private sector entities, and more strongly emphasizing program outcomes. We also discuss principles that leaders should consider adopting when transitioning to the PHIM, including cross-collaboration, community buy-in, human-centered assessment, autonomy and creativity, rapid experimentation and prototyping, and accountability to outcomes.
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