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1.
C L Griffin R P Musselman D B Yeates T N Raju R D Harshbarger R V Lourenco 《Laboratory animal science》1986,36(6):686-690
To conduct laboratory studies in unsedated animals that were similar anatomically and physiologically to man, five full term baboons (four Papio cynocephalus anubis, one Papio cynocephalus cynocephalus) were hand-reared. These infants were used as unsedated animal models in short-term lung clearance studies conducted from birth to 2 years of age. The hand-rearing techniques described here encouraged the formation of an infant-human rearer bond that permitted us to control the level of expressed aggressive behavior as the infant matured. These techniques resulted in baboons which displayed subordinate behavior, showed positive reception to human contact (without evidence of negative stereotypic behavioral anomalies) and remained cooperative subjects for our investigations of short-term pulmonary clearance. The baboons generally were above average in weight in comparison to conspecifically-reared baboons of similar age, sex and species. Representative lung retention curves presented on one baboon demonstrate the feasibility of lung clearance studies in these hand-reared animals. Due to its suitability for unsedated studies, this baboon model may be considered for other types of laboratory investigations. 相似文献
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Meagan E. Valentine Brandon D. Kirby Thomas R. Withers Shannon L. Johnson Timothy E. Long Youai Hao Joseph S. Lam Richard M. Niles Hongwei D. Yu 《Microbial biotechnology》2020,13(1):162-175
Alginate is an important polysaccharide that is commonly used as a gelling agent in foods, cosmetics and healthcare products. Currently, all alginate used commercially is extracted from brown seaweed. However, with environmental changes such as increasing ocean temperature and the increasing number of biotechnological uses of alginates with specific properties, there is an emerging need for more reliable and customizable sources of alginate. An alternative to seaweed for alginate production is Pseudomonas aeruginosa, a common Gram-negative bacterium that can form alginate-containing biofilms. However, P. aeruginosa is an opportunistic pathogen that can cause life-threatening infections in immunocompromised patients. Therefore, we sought to engineer a non-pathogenic P. aeruginosa strain that is safe for commercial production of alginate. Using a homologous recombination strategy, we sequentially deleted five key pathogenicity genes from the P. aeruginosa chromosome, resulting in the marker-free strain PGN5. Intraperitoneal injection of mice with PGN5 resulted in 0% mortality, while injection with wild-type P. aeruginosa resulted in 95% mortality, providing evidence that the systemic virulence of PGN5 is highly attenuated. Importantly, PGN5 produces large amounts of alginate in response to overexpression of MucE, an activator of alginate biosynthesis. The alginate produced by PGN5 is structurally identical to alginate produced by wild-type P. aeruginosa, indicating that the alginate biosynthetic pathway remains functional in this modified strain. The genetic versatility of P. aeruginosa will allow us to further engineer PGN5 to produce alginates with specific chemical compositions and physical properties to meet different industrial and biomedical needs. 相似文献
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Meagan F. Oldfather Matthew M. Kling Seema N. Sheth Nancy C. Emery David D. Ackerly 《Global Change Biology》2020,26(3):1055-1067
The impacts of climate change have re‐energized interest in understanding the role of climate in setting species geographic range edges. Despite the strong focus on species' distributions in ecology and evolution, defining a species range edge is theoretically and empirically difficult. The challenge of determining a range edge and its relationship to climate is in part driven by the nested nature of geography and the multidimensionality of climate, which together generate complex patterns of both climate and biotic distributions across landscapes. Because range‐limiting processes occur in both geographic and climate space, the relationship between these two spaces plays a critical role in setting range limits. With both conceptual and empirical support, we argue that three factors—climate heterogeneity, collinearity among climate variables, and spatial scale—interact to shape the spatial structure of range edges along climate gradients, and we discuss several ways that these factors influence the stability of species range edges with a changing climate. We demonstrate that geographic and climate edges are often not concordant across species ranges. Furthermore, high climate heterogeneity and low climate collinearity across landscapes increase the spectrum of possible relationships between geographic and climatic space, suggesting that geographic range edges and climatic niche limits correspond less frequently than we may expect. More empirical explorations of how the complexity of real landscapes shapes the ecological and evolutionary processes that determine species range edges will advance the development of range limit theory and its applications to biodiversity conservation in the context of changing climate. 相似文献
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Erin P. Price Derek S. Sarovich Jessica R. Webb Jennifer L. Ginther Mark Mayo James M. Cook Meagan L. Seymour Mirjam Kaestli Vanessa Theobald Carina M. Hall Joseph D. Busch Jeffrey T. Foster Paul Keim David M. Wagner Apichai Tuanyok Talima Pearson Bart J. Currie 《PloS one》2013,8(8)
Burkholderia ubonensis is an environmental bacterium belonging to the Burkholderia cepacia complex (Bcc), a group of genetically related organisms that are associated with opportunistic but generally nonfatal infections in healthy individuals. In contrast, the near-neighbour species Burkholderia pseudomallei causes melioidosis, a disease that can be fatal in up to 95% of cases if left untreated. B. ubonensis is frequently misidentified as B. pseudomallei from soil samples using selective culturing on Ashdown’s medium, reflecting both the shared environmental niche and morphological similarities of these species. Additionally, B. ubonensis shows potential as an important biocontrol agent in B. pseudomallei-endemic regions as certain strains possess antagonistic properties towards B. pseudomallei. Current methods for characterising B. ubonensis are laborious, time-consuming and costly, and as such this bacterium remains poorly studied. The aim of our study was to develop a rapid and inexpensive real-time PCR-based assay specific for B. ubonensis. We demonstrate that a novel B. ubonensis-specific assay, Bu550, accurately differentiates B. ubonensis from B. pseudomallei and other species that grow on selective Ashdown’s agar. We anticipate that Bu550 will catalyse research on B. ubonensis by enabling rapid identification of this organism from Ashdown’s-positive colonies that are not B. pseudomallei. 相似文献
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Amrita L. Sherlekar Abbey Janssen Meagan S. Siehr Pamela K. Koo Laura Caflisch May Boggess Robyn Lints 《PloS one》2013,8(4)
Background
Mating behaviors in simple invertebrate model organisms represent tractable paradigms for understanding the neural bases of sex-specific behaviors, decision-making and sensorimotor integration. However, there are few examples where such neural circuits have been defined at high resolution or interrogated.Methodology/Principal Findings
Here we exploit the simplicity of the nematode Caenorhabditis elegans to define the neural circuits underlying the male’s decision to initiate mating in response to contact with a mate. Mate contact is sensed by male-specific sensilla of the tail, the rays, which subsequently induce and guide a contact-based search of the hermaphrodite’s surface for the vulva (the vulva search). Atypically, search locomotion has a backward directional bias so its implementation requires overcoming an intrinsic bias for forward movement, set by activity of the sex-shared locomotory system. Using optogenetics, cell-specific ablation- and mutant behavioral analyses, we show that the male makes this shift by manipulating the activity of command cells within this sex-shared locomotory system. The rays control the command interneurons through the male-specific, decision-making interneuron PVY and its auxiliary cell PVX. Unlike many sex-shared pathways, PVY/PVX regulate the command cells via cholinergic, rather than glutamatergic transmission, a feature that likely contributes to response specificity and coordinates directional movement with other cholinergic-dependent motor behaviors of the mating sequence. PVY/PVX preferentially activate the backward, and not forward, command cells because of a bias in synaptic inputs and the distribution of key cholinergic receptors (encoded by the genes acr-18, acr-16 and unc-29) in favor of the backward command cells.Conclusion/Significance
Our interrogation of male neural circuits reveals that a sex-specific response to the opposite sex is conferred by a male-specific pathway that renders subordinate, sex-shared motor programs responsive to mate cues. Circuit modifications of these types may make prominent contributions to natural variations in behavior that ultimately bring about speciation. 相似文献8.
Jo Meagan Garner Meiyun Fan Chuan He Yang Ziyun Du Michelle Sims Andrew M. Davidoff Lawrence M. Pfeffer 《The Journal of biological chemistry》2013,288(36):26167-26176
Malignant gliomas are locally aggressive, highly vascular tumors that have a dismal prognosis, and present therapies provide little improvement in the disease course and outcome. Many types of malignancies, including glioblastoma, originate from a population of cancer stem cells (CSCs) that are able to initiate and maintain tumors. Although CSCs only represent a small fraction of cells within a tumor, their high tumor-initiating capacity and therapeutic resistance drives tumorigenesis. Therefore, it is imperative to identify pathways associated with CSCs to devise strategies to selectively target them. In this study, we describe a novel relationship between glioblastoma CSCs and the Notch pathway, which involves the constitutive activation of STAT3 and NF-κB signaling. Glioma CSCs were isolated and maintained in vitro using an adherent culture system, and the biological properties were compared with the traditional cultures of CSCs grown as multicellular spheres under nonadherent culture conditions. Interestingly, both adherent and spheroid glioma CSCs show constitutive activation of the STAT3/NF-κB signaling pathway and up-regulation of STAT3- and NF-κB-dependent genes. Gene expression profiling also identified components of the Notch pathway as being deregulated in glioma CSCs, and the deregulated expression of these genes was sensitive to treatment with STAT3 and NF-κB inhibitors. This finding is particularly important because Notch signaling appears to play a key role in CSCs in a variety of cancers and controls cell fate determination, survival, proliferation, and the maintenance of stem cells. The constitutive activation of STAT3 and NF-κB signaling pathways that leads to the regulation of Notch pathway genes in glioma CSCs identifies novel therapeutic targets for the treatment of glioma. 相似文献
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Megan J. Agajanian Matthew P. Walker Alison D. Axtman Roberta R. Ruela-de-Sousa D. Stephen Serafin Alex D. Rabinowitz David M. Graham Meagan B. Ryan Tigist Tamir Yuko Nakamichi Melissa V. Gammons James M. Bennett Rafael M. Couñago David H. Drewry Jonathan M. Elkins Carina Gileadi Opher Gileadi Paulo H. Godoi Michael B. Major 《Cell reports》2019,26(1):79-93.e8