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FEMS Immunol Med Microbiol,
2005]
Recently, the use of invertebrate models of infection has given exciting insights into host-pathogen interaction for a number of bacteria. In particular, this has revealed important factors of the host response with remarkable parallels in higher organisms. Here, we review the advances attained in the elucidation of virulence determinants of a major human pathogen, Staphylococcus aureus, in relation to the invertebrate models thus far applied, the silkworm (Bombyx mori), the fruit fly (Drosophila melanogaster) and the roundworm (Caenorhabditis elegans). Also, the major pathways of host defence are covered in light of the response to S. aureus and the similarities and divergences in innate immunity of vertebrates and invertebrates. Consequently, we comparatively consider pathogen recognition receptors, signal transduction pathways (including Toll, Imd and others), and the humoral and cellular antimicrobial effectors. The technically convenient and ethically acceptable invertebrates appear as a valuable first tool to discriminate molecules participating from both sides of the host-S. aureus interaction as well as a high throughput method for antimicrobial screening.
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[
Adv Genet,
2015]
Food availability determines developmental rate, behavior, and survival of animals. Animals that enter diapause or hibernate in response to lack of food have a double advantage: they are able to adapt to environmental and cellular challenges and survive to these challenges for a prolonged time. The metabolic and physiological adaptations that make possible diapause and hibernation also provide a favorable cellular environment for tissue protection. This review highlights the benefits of dormancy on neuronal protection in the model organism Caenorhabditis elegans and small mammals such as squirrels. Additionally, I discuss the link between metabolic restructuring occurring in diapause and changes in gene expression with the increased capacity of diapausing animals to protect neurons from degeneration and potentially foster their regeneration.
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[
International Worm Meeting,
2015]
RUNX transcription factors play pivotal roles in mammalian development and carcinogenesis. Proper expression and regulation of RUNX foster proper organismal development and prevent cancer development. We previously reported that RNT-1, the C. elegans sole RUNX homolog protein, is degraded by ubiquitin-proteasome system (UPS) and is stabilized upon acute oxidative stress response by repressing UPS. Nevertheless, other mechanisms of RNT-1 degradation remain elusive. To solve this question, we tried to find the novel regulator of RNT-1 stability and understand its mechanism. We isolated novel regulator genes involved in RNT-1 stabilization by random mutagenesis. Now we are characterizing RNT-1-stabilized mutants, and investigating the effect of the mutation on RNT-1 stability. Our study will contribute to further understanding of RUNX-involved development and carcinogenesis.
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[
International Worm Meeting,
2017]
High enrollment classes (>50 students) have historically been associated with lower student engagement and higher failure rates than lower enrollment classes. Active learning has been demonstrated to increase student engagement and, indirectly, student persistence. In addition, faculty who use high engagement in their classrooms become pedagogical role models for the future teachers who are enrolled in their courses. By initiating an Active Engagement Academy at Texas Woman's University, faculty who teach large lecture classes have been recruited and trained to use active learning and teaching methods to foster student engagement, academic success, and retention. The Active Engagement Academy model will be self-perpetuating as participating faculty will become role models within their academic departments for other faculty and for the teacher candidates enrolled in their courses. This presentation will provide a model and framework for other instructors who wish to promote active engagement in their institution's classrooms, including the rationale, recruiting information, workshop plans, and designs for active engagement implementations and measurements for intervention success.
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Ageing Res Rev,
2005]
Germline immortality is a topic that has intrigued theoretical biologists interested in aging for over a century. The germ cell lineage can be passed from one generation to the next, indefinitely. In contrast, somatic cells are typically only needed for a single generation and are then discarded. Germ cells may, therefore, harbor rejuvenation mechanisms that enable them to proliferate for eons. Such processes are thought to be either absent from or down-regulated in somatic cells, although cell non-autonomous forms of rejuvenation are formally possible. A thorough description of mechanisms that foster eternal youth in germ cells is lacking. The mysteries of germline immortality are being addressed in the nematode Caenorhabditis elegans by studying mutants that reproduce normally for several generations but eventually become sterile. The mortal germline mutants probably become sterile as a consequence of accumulating various forms of heritable cellular damage. Such mutants are abundant, indicating that several different biochemical pathways are required to rejuvenate the germline. Thus, forward genetics should help to define mechanisms that enable the germline to achieve immortality.
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Dis Model Mech,
2021]
Sarcopenia encompasses a progressive decline in muscle quantity and quality. Given its close association with aging, it may represent a valuable healthspan marker. Given the commonalities with human muscle structure and facile visualization possibilities, C. elegans represents an attractive model for studying the relationship between sarcopenia and healthspan. However, classical visual assessment of muscle architecture is subjective and has low throughput. To resolve this, we have developed an image analysis pipeline for the quantification of muscle integrity in confocal microscopy images from a cohort of aging myosin::GFP reporter worms. We extracted a variety of morphological descriptors and found a subset to scale linearly with age. This allowed establishing a linear model that predicts biological age from a morphological muscle signature. To validate the model, we evaluated muscle architecture in long-lived worms that are known to experience delayed sarcopenia by targeted knockdown of the
daf-2 gene. We conclude that quantitative microscopy allows for staging sarcopenia in C. elegans and may foster the development of image-based screens to identify modulators that mitigate age-related muscle frailty and thus improve healthspan in C. elegans.
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J Undergrad Neurosci Educ,
2018]
Inquiry based research experiences are thought to increase learning gains in biology, STEM retention, and confidence in students of diverse backgrounds. Furthermore, such research experiences within the first year of college may foster increased student retention and interest in biology. However, providing first year students in biology labs with inquiry-based experiences is challenging given demands of large student enrollments, restricted lab space, and instructor time. Thus, we aimed to integrate a small neurobiology themed research experience within a three-week modular, first-year biology laboratory setting. For this, students first performed a whole class lab examining the effects of ethanol on movement and associative learning. Using skills they acquired, the students devised, executed, and presented their self-designed experiments and results. Using pre-and post-course surveys, we analyzed student attitudes on their experiences, including technical skills, inquiry-based learning styles in which experimental outcomes are often unknown, and research in their first year of biology. Analyzing data collected for three years, we found that students self-reported gains in technical skills and positive attitudes toward inquiry-based learning. In contrast, we found that students did not self-report increased interest in research experiences in general.
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Moraru, Ion, Mohler, William A., Duzy, Glenn, Isaacson, Ariel B., Morgan, Frank, Vasilescu, Dan, Dutton, Jeffrey
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International Worm Meeting,
2011]
All wild-type C. elegans embryos re-enact the same series of cell divisions, deaths, movements and fates within a nearly identical space and time-scale. 4-dimensional recordings of embryos expressing single fluorescent transgenes are, therefore, conceptually superimposable for synchronized comparison and correlation. Technical hurdles that prevent such comparisons from being more commonly useful include diverse image data types, the sheer size of the data, and the likelihood that any single embryo might vary slightly in its spatial dimensions, its rate of development, or stochastic quirks in its cells' positioning and movements. Our system allows anyone in the community to access the contents of multi-gigabyte data sets via a web-facilitated file-sharing interface, downloading only those fragments of 4D movies that are of particular interest to each viewer. Visualized scenes can combine an arbitrary collection of different genotypes presented in synchrony, with interactive controls for fitting each to a common spatiotemporal frame. A variety of public-domain algorithms packaged within the GLOWormJ adaptation of ImageJ permit enhancements, measurements, and annotation of features within each embryo. The saved adjustments and markings for any embryo in the collection can be recalled along with those of other embryos to foster progressively better comparisons and richer insights.
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FASEB J,
2016]
Nematodes lack a heme biosynthetic pathway and must acquire heme from exogenous sources. Given the indispensable role of heme, this auxotrophy may be exploited to develop drugs that interfere with heme uptake in parasites. Although multiple heme-responsive genes (HRGs) have been characterized within the free-living nematode Caenorhabditis elegans, we have undertaken the first study of heme transport in Brugia malayi, a causative agent of lymphatic filariasis. Through functional assays in yeast, as well as heme analog, RNAi, and transcriptomic experiments, we have shown that the heme transporter HRG-1 (BmHRG-1) is indeed functional in B. malayi In addition, BmHRG-1 localizes both to the endocytic compartments and cell membrane when expressed in yeast cells. Transcriptomic sequencing revealed that BmHRG-1, BmHRG-2, and BmMRP-5 (all orthologs of HRGs in C. elegans) are down-regulated in heme-treated B. malayi, as compared to non-heme-treated control worms. Likely because of short gene lengths, multiple exons, other HRGs in B. malayi (BmHRG-3, -4, -5, and -6) remain unidentified. Although the precise mechanisms of heme homeostasis in a nematode with the ability to acquire heme remains unknown, this study clearly demonstrates that the filarial nematode B. malayi is capable of transporting exogenous heme.-Luck, A. N., Yuan, X., Voronin, D., Slatko, B. E., Hamza, I., Foster, J. M. Heme acquisition in the parasitic filarial nematode Brugia malayi.
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Witt S, Paclik D, Brattig NW, Seeberger P, Reinhardt A, Jolodar A, Garcia-Hernandez M, Hansmann J, Anandarajah EM, Ditgen D, Lorenz E, Soblik H, Elshazly Younis A, Liebau E
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Mol Biochem Parasitol,
2018]
Helminths are complex pathogens that ensure their long-term survival by influencing the immune responses of their host. Excretory/secretory products (ESP) can exert immunoregulatory effects which foster parasite survival. Galectins represent a widespread group of -galactoside-binding proteins which are involved in a multitude of biological processes operative in parasite-host interaction. We had earlier identified seven galectins in Strongyloides ratti, four of them detected in the ESP of distinct developmental stages of the parasite. In the present report, we focused on the characterization of two of them, Sr-galectin-1 (Sr-Gal-1) and Sr-galectin-3 (Sr-Gal-3). While Sr-Gal-3 expression was strongest in parasitic females, Sr-Gal-1 was predominantly expressed in free-living females. Both proteins were cloned and recombinantly expressed in an E. coli expression system. Their glycan-binding activity was verified by haemagglutination and glycan array analysis. Furthermore, primary immunological activities of the Sr-galectins were initially investigated by the application of an in vitro mucosal 3D-culture model, comprising of mucosa-associated epithelial and dendritic cells. The Sr-galectins stimulated preferentially the release of the type 2 cytokines thymic stromal lymphopoietin and IL-22, a first indication for immunoregulatory activity. In addition, the Sr-galectins dose-dependently fostered cell migration. Our results confirm the importance of these carbohydrate-binding proteins in host-parasite-interaction by indicating possible interaction with the host mucosa-associated cells.