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In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
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Background: Complement proteins and activation products have been found associated with neuropathology in Alzheimer's disease (AD). Recently, a C5a receptor antagonist was shown to suppress neuropathology in two murine models of AD, Tg2576 and 3xTg. Previously, a genetic deficiency of C1q in the Tg2576 mouse model showed an accumulation of fibrillar plaques similar to the complement sufficient Tg2576, but reactive glia were significantly decreased and neuronal integrity was improved suggesting detrimental consequences for complement activation in AD. The goal of this study was to define the role of the classical complement activation pathway in the progression of pathology in the 3xTg mouse that develops tangles in addition to fibrillar plaques (more closely reflecting human AD pathology) and to assess the influence of complement in a model of AD with a higher level of complement hemolytic activity. Methods: 3xTg mice deficient in C1q (3xTgQ-/-) were generated, and both 3xTg and 3xTgQ-/-were backcrossed to the BUB mouse strain which has higher in vitro hemolytic complement activity. Mice were aged and perfused, and brain sections stained for pathological markers or analyzed for proinflammatory marker expression. Results: 3xTgQ-/-mice showed similar amounts of fibrillar amyloid, reactive glia and hyperphosphorylated tau as the C1q-sufficient 3xTg at the ages analyzed. However, 3xTg and 3xTgQ-/-on the BUB background developed pathology earlier than on the original 3xTg background, although the presence of C1q had no effect on neuropathological and pro-inflammatory markers. In contrast to that seen in other transgenic models of AD, C1q, C4 and C3 immunoreactivity was undetectable on the plaques of 3xTg in any background, although C3 was associated with reactive astrocytes surrounding the plaques. Importantly, properdin a component of the alternative complement pathway was associated with plaques in all models. Conclusions: In contrast to previously investigated transgenic models of AD, development of neuropathology in 3xTg mice, which progresses much slower than other murine models, may not be influenced by fibrillar amyloid mediated activation of the classical complement pathway, suggesting that the alternative complement pathway activation or a C3-independent cleavage of C5 could account for the detrimental effects in these mice that are prevented by the C5a receptor antagonist. Furthermore, the paucity of complement activation may be a factor in the slower kinetics of progression of pathology in the 3xTg model of this disease.
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Contribution of complement activation pathways to neuropathology differs among mouse models of Alzheimer's disease


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Collagen-induced arthritis is a B cell-mediated autoimmune disease. Recently published studies have demonstrated that in some rare cases pathogens can confer protection from autoimmunity. Trypanosoma brucei parasites are tsetse fly transmitted extracellular protozoans causing sleeping sickness disease in humans and Nagana in livestock in sub-Saharan endemic areas. In the past, we demonstrated that trypanosome infections impair B cell homeostasis and abolish vaccine-induced protection against unrelated antigens. Hence, here we hypothesized that trypanosome infection can affect the onset of CIA by specifically dampening specific B-cell responses and type II collagen antibody titers in DBA/1 prone mice. We observed a substantial delay in the onset of collagen-induced arthritis in T. brucei-infected DBA/1 mice that correlates with a drastic decrease of type II collagen titers of the different IgG isotypes in the serum. Treatment of infected mice with Berenil, a trypanocidal drug, restored the development of CIA-associated clinical symptoms. Interestingly, these data were confirmed by the challenge of immunized DBA/1 prone mice with T. brucei-infected tsetse flies. Together, these results demonstrate that T. brucei infection is impairing the maintenance of the antigen specific plasma B cell pool driving the development of CIA in DBA/1 prone mice.
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Experimental African Trypanosome Infection by Needle Passage or Natural Tsetse Fly Challenge Thwarts the Development of Collagen-Induced Arthritis in DBA/1 Prone Mice via an Impairment of Antigen Specific B Cell Autoantibody Titers


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Hospitals worldwide are facing an increasing incidence of hard-to-treat infections. Limiting infections and providing patients with optimal drug regimens require timely strain identification as well as virulence and drug-resistance profiling. Additionally, prophylactic interventions based on the identification of environmental sources of recurrent infections (e.g., contaminated sinks) and reconstruction of transmission chains (i.e., who infected whom) could help to reduce the incidence of nosocomial infections. WGS could hold the key to solving these issues. However, uptake in the clinic has been slow. Some major scientific and logistical challenges need to be solved before WGS fulfils its potential in clinical microbial diagnostics. In this review we identify major bottlenecks that need to be resolved for WGS to routinely inform clinical intervention and discuss possible solutions. Thanks to progress in high-throughput sequencing technologies over the last two decades, generating microbial genomes is now considered neither particularly challenging nor expensive. As a result, whole-genome sequencing (WGS) (see Glossary) has been championed as the obvious and inevitable future of diagnostics in multiple reviews and opinion pieces dating back to 2010 [1] [2] [3] [4] . Despite enthusiasm in the community, WGS diagnostics has not yet been widely adopted in clinical microbiology, which may seem at odds with the current suite of applications for which WGS has huge potential, and which are already widely used in the academic literature. Common applications of WGS in diagnostic microbiology include isolate characterization, antimicrobial resistance (AMR) profiling, and establishing the sources of recurrent infections and between-patient transmissions. All of these have obvious clinical relevance and provide case studies where WGS could, in principle, provide additional information and even replace the knowledge obtained through standard clinical microbiology techniques. This review reiterates the potential of WGS for clinical microbiology, but also its current limitations, and suggests possible solutions to some of the main bottlenecks to routine implementation. In particular, we argue that applying existing WGS pipelines developed for fundamental research is unlikely to produce the fast and robust tools required, and that new dedicated approaches are needed for WGS in the clinic. At the most basic level, WGS can be used to characterize a clinical isolate, informing on the likely species and/or subtype and allowing phylogenetic placement of a given sequence relative to an existing set of isolates. WGS-based strain identification gives a far superior resolution Highlights In principle, WGS can provide highly relevant information for clinical microbiology in near-real-time, from phenotype testing to tracking outbreaks. However, despite this promise, the uptake of WGS in the clinic has been limited to date, and future implementation is likely to be a slow process. The increasing information provided by WGS can cause conflict with traditional microbiological concepts and typing schemes. Decreasing raw sequencing costs have not translated into decreasing total costs for bacterial genomes, which have stabilised. Existing research pipelines are not suitable for the clinic, and bespoke clinical pipelines should be developed.
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From Theory to Practice: Translating Whole-Genome Sequencing (WGS) into the Clinic