29 research outputs found
A Review on Malicious URL Detection using Machine Learning Systems
Malicious web sites pretendsignificant danger to desktop security and privacy.These links become instrumental in giving partial or full system control to the attackers. This results in victim systems, which get easily infected and, attackers can utilize systems for various cyber-crimes such as stealing credentials, spamming, phishing, denial-of-service and many more such attack. Detection of such website is difficult because of thephishing campaigns and the efforts to avoid blacklists.To look for malicious URLs, the first step is usually to gather URLs that are liveon the Internet. There are various stages to detect this URLs such as collection of dataset, extracting feature using different feature extraction techniques and Classification of extracted feature. This paper focus on comparative analysis of malicious URL detection techniques
T Cell Responses to Neural Autoantigens Are Similar in Alzheimer’s Disease Patients and Age-Matched Healthy Controls
Alzheimer’s disease (AD), a chronic multifactorial and complex neurodegenerative disorder is a leading cause of dementia. Recently, neuroinflammation has been hypothesized as a contributing factor to AD pathogenesis. The role of adaptive immune responses against neuronal antigens, which can either confer protection or induce damage in AD, has not been fully characterized. Here, we measured T cell responses to several potential antigens of neural origin including amyloid precursor protein (APP), amyloid beta (Aβ), tau, α-synuclein, and transactive response DNA binding protein (TDP-43) in patients with AD and age-matched healthy controls (HC). Antigen-specific T cell reactivity was detected for all tested antigens, and response to tau-derived epitopes was particularly strong, but no significant differences between individuals with AD and age-matched HC were identified. We also did not observe any correlation between the antigen-specific T cell responses and clinical variables including age, gender, years since diagnosis and cognitive score. Additionally, further characterization did not reveal any differences in the relative frequency of major Peripheral Blood Mononuclear Cells (PBMC) subsets, or in the expression of genes between AD patients and HC. These observations have not identified a key role of neuronal antigen-specific T cell responses in AD
α-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson’s disease
A diagnosis of motor Parkinson’s disease (PD) is preceded by a prolonged premotor phase with accumulating neuronal damage. Here we examined the temporal relation between α-synuclein (α-syn) T cell reactivity and PD. A longitudinal case study revealed that elevated α-syn-specific T cell responses were detected prior to the diagnosis of motor PD, and declined after. The relationship between T cell reactivity and early PD in two independent cohorts showed that α-syn-specific T cell responses were highest shortly after diagnosis of motor PD and then decreased. Additional analysis revealed significant association of α-syn-specific T cell responses with age and lower levodopa equivalent dose. These results confirm the presence of α-syn-reactive T cells in PD and show that they are most abundant immediately after diagnosis of motor PD. These cells may be present years before the diagnosis of motor PD, suggesting avenues of investigation into PD pathogenesis and potential early diagnosis
Proteomic Analysis of Chikungunya Virus Infected Microgial Cells
Chikungunya virus (CHIKV) is a recently re-emerged public health problem in many countries bordering the Indian Ocean and elsewhere. Chikungunya fever is a relatively self limiting febrile disease, but the consequences of chikungunya fever can include a long lasting, debilitating arthralgia, and occasional neurological involvement has been reported. Macrophages have been implicated as an important cell target of CHIKV with regards to both their role as an immune mediator, as well evidence pointing to long term viral persistence in these cells. Microglial cells are the resident brain macrophages, and so this study sought to define the proteomic changes in a human microglial cell line (CHME-5) in response to CHIKV infection. GeLC-MS/MS analysis of CHIKV infected and mock infected cells identified some 1455 individual proteins, of which 90 proteins, belonging to diverse cellular pathways, were significantly down regulated at a significance level of p<0.01. Analysis of the protein profile in response to infection did not support a global inhibition of either normal or IRES-mediated translation, but was consistent with the targeting of specific cellular pathways including those regulating innate antiviral mechanisms
The TCR repertoire of α-synuclein-specific T cells in Parkinson’s disease is surprisingly diverse
The self-antigen α-synuclein (α-syn) was recently shown to be associated with Parkinson’s disease (PD). Here we mapped the T cell receptor (TCR) repertoire of α-syn-specific T cells from six PD patients. The self-antigen α-syn-specific repertoire was compared to the repertoire of T cells specific for pertussis (PT), as a representative foreign antigen that most individuals are exposed to, revealing that the repertoire for α-syn was as diverse as the repertoire for PT. The diversity of PT-specific clonotypes was similar between individuals with PD diagnosis and age-matched healthy controls. We found that the TCR repertoire was specific to each PD patient, and no shared TCRs among patients were defined, likely due to differences in HLA expression that select for different subsets of epitope-specific TCR rearrangements. This study provides the first characterization of α-syn-specific TCR clonotypes in individuals with PD. Antigen-specific TCRs can serve as immunotherapeutics and diagnostics, and means to track longitudinal changes in specific T cells, and disease progression
Widespread Tau-Specific CD4 T Cell Reactivity in the General Population
Tau protein is found to be aggregated and hyperphosphorylated (p-tau) in many neurologic disorders, including Parkinson disease (PD) and related parkinsonisms, Alzheimer disease, traumatic brain injury, and even in normal aging. Although not known to produce autoimmune responses, we hypothesized that the appearance of aggregated tau and p-tau with disease could activate the immune system. We thus compared T cell responses to tau and p-tau–derived peptides between PD patients, age-matched healthy controls, and young healthy controls (<35 y old; who are less likely to have high levels of tau aggregates). All groups exhibited CD4+ T cell responses to tau-derived peptides, which were associated with secretion of IFN-γ, IL-5, and/or IL-4. The PD and control participants exhibited a similar magnitude and breadth of responses. Some tau-derived epitopes, consisting of both unmodified and p-tau residues, were more highly represented in PD participants. These results were verified in an independent set of PD and control donors (either age-matched or young controls). Thus, T cells recognizing tau epitopes escape central and peripheral tolerance in relatively high numbers, and the magnitude and nature of these responses are not modulated by age or PD disease
Characterization of Chikungunya Virus Induced Host Response in a Mouse Model of Viral Myositis
Virus replicon particle vaccines expressing nucleoprotein of influenza A virus mediate enhanced inflammatory responses in pigs.
Studies in the mouse model indicate that the nucleoprotein of influenza A virus represents an interesting vaccine antigen being well conserved across subtypes of influenza virus but still able to induce protective immune responses. Here we show that immunizations of pigs with vesicular stomatitis virus- and classical swine fever virus-derived replicon (VRP) particles expressing the nucleoprotein (NP) of H1N1 A/swine/Belzig/2/01 induced potent antibody and T-cell responses against influenza A virus. In contrast to a conventional whole inactivated virus vaccine, the VRP vaccines induced both NP-specific CD4 and CD8 T cells responses, including interferon-γ and tumor-necrosis-factor dual-secreting cell. Although T-cells and antibody responses were cross-reactive with the heterologous H1N2 A/swine/Bakum/R757/2010 challenge virus, they did not provide protection against infection. Surprisingly, vaccinated pigs showed enhanced virus shedding, lung inflammation and increased levels of systemic and lung interferon-α as well as elevated lung interleukin-6. In conclusion, our study shows that NP, although efficacious in the mouse model, appears not to be a promising stand-alone vaccine antigen for pigs