4,530 research outputs found

    MicroRNAs in Pancreatic Ductal Adenocarcinoma: New Approaches For Better Diagnosis And Therapy

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    Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with less than an 8% 5-year survival rate, which has remained unchanged over the last 50 years. Early detection is particularly difficult due to the lack of disease-specific symptoms and reliable diagnostic biomarkers. Multimodality treatment including chemotherapy, radiotherapy (used sparingly) and surgery has become the standard of care for patients with PDAC. Carbohydrate antigen 19-9 (CA 19-9) is the most common diagnostic biomarker; however, it is not specific enough for asymptomatic patients. MicroRNAs (miRs/miRNAs) are small non-encoding RNA molecules, which have been related with PDAC progression and metastasis. In particular, miR-21, miR-221, miR-155 and miR-126 have to date been shown to be highly dysregulated in human malignancies including PDAC and are involved in numerous cancer-related mechanisms such as cell growth, differentiation, metastasis, invasion, and cell death. The aim of this thesis was to examine the mode of action of miR-21, miR-221, miR-155 and miR-126 in vitro for improved diagnosis and treatment of PDAC and specifically, investigate the role of the oncogenic miR-21 in cellular proliferation, migration, invasion, apoptosis, cell cycle arrest, senescence, protein content and mitochondrial function by using CRISPR/Cas9 knockouts. The findings provide promising new insights into the metastatic predisposition of PDAC through the evaluation of specific miR signature profiles (in vitro). Such miR signatures could prompt a pioneer precision medicine approach for individual PDAC cases and allow a more effective early diagnosis and control of PDAC, facilitating more effective treatment

    Comparative study of the effects of Montanide™ ISA 763A VG and ISA 763B VG adjuvants on the immune response against Streptococcus agalactiae in Nile tilapia (Oreochromis niloticus)

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    Acknowledgements We are highly grateful to thank Seppic, France, for providing us with the commercial products of MontanideTM ISA 763A VG and MontanideTM 437 ISA 763B VG. Funding This research project was financially supported by Mahasarakham University (Grant No. 6517022Peer reviewedPostprin

    Regulation of microglia polarization after cerebral ischemia

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    Stroke ranks second as a leading cause of death and permanent disability globally. Microglia, innate immune cells in the brain, respond rapidly to ischemic injury, triggering a robust and persistent neuroinflammatory reaction throughout the disease’s progression. Neuroinflammation plays a critical role in the mechanism of secondary injury in ischemic stroke and is a significant controllable factor. Microglia activation takes on two general phenotypes: the pro-inflammatory M1 type and the anti-inflammatory M2 type, although the reality is more complex. The regulation of microglia phenotype is crucial to controlling the neuroinflammatory response. This review summarized the key molecules and mechanisms of microglia polarization, function, and phenotypic transformation following cerebral ischemia, with a focus on the influence of autophagy on microglia polarization. The goal is to provide a reference for the development of new targets for the treatment for ischemic stroke treatment based on the regulation of microglia polarization

    Uncovering the candidate genes related to sheep body weight using multi-trait genome-wide association analysis

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    In sheep, body weight is an economically important trait. This study sought to map genetic loci related to weaning weight and yearling weight. To this end, a single-trait and multi-trait genome-wide association study (GWAS) was performed using a high-density 600 K single nucleotide polymorphism (SNP) chip. The results showed that 43 and 56 SNPs were significantly associated with weaning weight and yearling weight, respectively. A region associated with both weaning and yearling traits (OARX: 6.74–7.04 Mb) was identified, suggesting that the same genes could play a role in regulating both these traits. This region was found to contain three genes (TBL1X, SHROOM2 and GPR143). The most significant SNP was Affx-281066395, located at 6.94 Mb (p = 1.70 × 10−17), corresponding to the SHROOM2 gene. We also identified 93 novel SNPs elated to sheep weight using multi-trait GWAS analysis. A new genomic region (OAR10: 76.04–77.23 Mb) with 22 significant SNPs were discovered. Combining transcriptomic data from multiple tissues and genomic data in sheep, we found the HINT1, ASB11 and GPR143 genes may involve in sheep body weight. So, multi-omic anlaysis is a valuable strategy identifying candidate genes related to body weight

    Differential gene expression of Asian citrus psyllids infected with ‘Ca. Liberibacter asiaticus’ reveals hyper-susceptibility to invasion by instar fourth-fifth and teneral adult stages

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    The bacterial pathogen Candidatus Liberibacter asiaticus (CLas) is the causal agent of citrus greening disease. This unusual plant pathogenic bacterium also infects its psyllid host, the Asian citrus psyllid (ACP). To investigate gene expression profiles with a focus on genes involved in infection and circulation within the psyllid host of CLas, RNA-seq libraries were constructed from CLas-infected and CLas-free ACP representing the five different developmental stages, namely, nymphal instars 1-2, 3, and 4-5, and teneral and mature adults. The Gbp paired-end reads (296) representing the transcriptional landscape of ACP across all life stages and the official gene set (OGSv3) were annotated based on the chromosomal-length v3 reference genome and used for de novo transcript discovery resulting in 25,410 genes with 124,177 isoforms. Differential expression analysis across all ACP developmental stages revealed instar-specific responses to CLas infection, with greater overall responses by nymphal instars, compared to mature adults. More genes were over-or under-expressed in the 4-5th nymphal instars and young (teneral) adults than in instars 1-3, or mature adults, indicating that late immature instars and young maturing adults were highly responsive to CLas infection. Genes identified with potential for direct or indirect involvement in the ACP-CLas circulative, propagative transmission pathway were predominantly responsive during early invasion and infection processes and included canonical cytoskeletal remodeling and endo-exocytosis pathway genes. Genes with predicted functions in defense, development, and immunity exhibited the greatest responsiveness to CLas infection. These results shed new light on ACP-CLas interactions essential for pathogenesis of the psyllid host, some that share striking similarities with effector protein-animal host mechanisms reported for other culturable and/or fastidious bacterial- or viral- host pathosystems

    2023-2024 Catalog

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    The 2023-2024 Governors State University Undergraduate and Graduate Catalog is a comprehensive listing of current information regarding:Degree RequirementsCourse OfferingsUndergraduate and Graduate Rules and Regulation

    Cardiovascular Dysfunction and the ATP-Adenosine Axis in Trauma

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    Introduction Trauma is a significant contributor to global mortality and morbidity. Outcomes have improved over the last several decades, but there are still a population of patients who die after surviving their initial injuries. The cardiovascular system is vulnerable to the effects of both shock and inflammation but has not been adequately investigated. The purines ATP and adenosine have critical roles in metabolism, immunity, and the regulation of the cardiovascular system and may be pivotal in understanding why patients still die. Methods A retrospective analysis was used to describe the population with cardiovascular dysfunction. A prospective study design was used in the measurement of ATP and adenosine. Proteomic analysis was performed on samples from a prospectively maintained trauma biobank. Results Cardiovascular dysfunction was the dominant organ system to develop dysfunction following trauma and occurred in one third of trauma patients admitted to critical care. It was associated with a significant mortality and was manifest early in the disease process. ATP was associated with organ dysfunction; however, adenosine did not show any relationship to clinical outcome in this study. Proteomic analysis identified three distinct proteins that were upregulated in CVD; K2013, ATPase WRNIP1, and heat shock 70 kDa protein. K2013 has not yet been characterised and may be a novel biomarker of cardiovascular pathology. The role of heat shock 70 kDa protein in cardiovascular pathology has been documented in other pathologies, but this the first time it has been associated with cardiovascular dysfunction in trauma. 5 Conclusion Cardiovascular dysfunction is a phenotype of organ dysfunction that has not been fully described in the literature. It is associated with poor clinical outcomes, and can be predicted early. The ATP-adenosine axis did not influence the development of cardiovascular dysfunction. There was a distinct pattern of protein upregulation that differentiated patients who developed cardiovascular dysfunction

    Assessing the immunomodulatory and haemostatic role of platelets in the type 2 inflammatory response to Schistosoma mansoni

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    Beyond their role in haemostasis, platelets have been shown to be strongly immunomodulatory, particularly in type 1 inflammatory responses to bacteria and viruses. However, the role of platelets in type 2 inflammation, that characterises helminth infection and allergy is poorly understood. More than 200 million people globally are chronically infected with schistosome parasites which has a massive burden of >3 million disability adjusted life years. Despite large (~1cm long) worms residing in the vasculature for 5-10 years, they do not induce severe inflammation or coagulation. However, infected individuals display a plethora of debilitating symptoms including hepatosplenomegaly and intestinal haemorrhaging due to thousands of schistosome eggs transiting through and lodging within host tissues. This thesis aims to assess the haemostatic alterations and functional consequences of platelet-immune cell cross-talk in schistosomiasis. We used a murine model of chronic Schistosoma mansoni infection to examine specific platelet-leukocyte interactions and the effect these have on inflammation. Chronic schistosome infection induces thrombocytopenia (~500x10^3/mm^3) that persists after drug-mediated worm clearance. In vivo platelet tracking revealed accelerated hepatic and splenic platelet clearance in schistosome infection, and this occurred in an FcγR-independent manner. Furthermore, there was a significant increase in platelets aggregating with specific hepatic macrophage subsets (Ly6Cˡᵒ MHCIIˡᵒ RELMαʰⁱ). Live cell imaging in vitro experiments revealed that platelets enhanced the phagocytic ability of M2 macrophages without altering MHCII or RELMα expression. Surprisingly, platelets from schistosome-infected mice spontaneously aggregated in the absence of exogenous agonists despite not having an activated platelet phenotype, yet show prolonged clotting time. We used multiple experimental strategies to deplete or increase platelet numbers in schistosome infection, and this highlighted the challenges of separating the haemostatic and immunological roles of platelets in vivo. Work in this thesis demonstrates how schistosome infection disrupts platelet lifespan and functionality, whilst promoting enhanced interactions with immune cells

    Gonads without glp-1: Silencing glp-1 in the Male Somatic Gonad in Caenorhabditis elegans

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    In C. elegans, the gene glp-1 encodes for a Notch receptor called GLP-1, one of two found in C. elegans’ genome. The gene has been previously implicated in the development of the hermaphroditic germline as well as playing a role in the mitosis/meiosis decision. Genetic screening has further identified it as potentially playing a role in the development of the male somatic gonad, making it an ideal candidate for a reverse genetic. We did this by silencing glp-1 and observing if any alterations to the gonad’s phenotype occur. Normally this could be done by performing a gene knockout. However, due to the nature of Notch receptors’ overall role in the regulation of tissue development, it is an essential gene, and silencing it would result in worms dying as embryos, long before a gonad capable of being studied could form. In order to conduct a knockdown study, CRISPR-Cas was used to tag GLP-1 at its C-terminus with green fluorescent protein (GFP). In a separate strain of worms, degron, a method used for targeting proteins tagged with GFP for ubiquination and lysis, was placed under a promoter specific to the gonad. When the two strains are crossed, they will result in a worm that has functional GLP-1 in all tissues except for the gonad. In order to resolve the sex ratio issue and focus on the development of the male gonad, which has been neglected in the literature, a mutant strain of him-8 worms that produced offspring with a ratio of three males for every ten viable was cultivated. The bulk of our work was spent crossing the degron strain with the him-8 strain, resulting in a new strain of worms that express degron in the gonad and are disproportionately likely to be male. By coupling this strain with the use of CRISPR to tag any gene of interest with GFP, a gonad-specific knockdown study can be performed not only for glp-1 but for any gene expressed in the gonad, essential or not. We crossed the new strain with degron and the mutant him-8 with the glp-1::GFP worms, generating both a produce a worm homozygous for all three genes, which should thus contain adult male worms without GLP-1 in their gonads and a strain with him-8 and glp-1::GFP but not degron, allowing us easy access to a source of a male control group. These we will examine for alterations against the N2 male gonad. In doing so, we will hopefully further understand Notch receptors’ role both in the development of the male gonad as well as in general tissue development
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