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- Type:
- Article
- Description/Abstract:
- Organisms in the genus Pneumocystis are ubiquitous, opportunistic pathogenic fungi capable of causing a lethal pneumonia in immunocompromised mammalian hosts. Pneumocystis spp. are unique members of the fungal kingdom due to the absence of ergosterol in their cellular membranes. Although these organisms were thought to obtain cholesterol by scavenging, transcriptional analyses indicate that Pneumocystis carinii encodes gene homologs involved in sterol biosynthesis. To better understand the sterol pathway in these uncultivable fungi, yeast deletion strains were used to interrogate the function and localization of P. carinii lanosterol synthase (ERG7). The expression of PcErg7p in an ERG7-null mutant of the yeast Saccharomyces cerevisiae did not alter its growth rate and produced a functional lanosterol synthase, as evidenced by the presence of lanosterol detected by gas chromatographic analysis in levels comparable to that produced by the yeast enzyme. Western blotting and fluorescence microscopy revealed that, like the S. cerevisiae Erg7p, the PcErg7p localized to lipid particles in yeast. Using fluorescence microscopy, we show for the first time the presence of apparent lipid particles in P. carinii and the localization of PcErg7p to lipid particles in P. carinii. The detection of lipid particles in P. carinii and their association with PcErg7p therein provide strong evidence that the enzyme serves a similar function in P. carinii. Moreover, the yeast heterologous system should be a useful tool for further analysis of the P. carinii sterol pathway.
- Creator/Author:
- Grant, Tiffany
- Submitter:
- Tiffany Grant
- Date Uploaded:
- 04/14/2016
- Date Modified:
- 04/14/2016
- License:
- All rights reserved
-
- Type:
- Article
- Description/Abstract:
- Members of the fungal genus Pneumocystis colonize healthy mammalian hosts without causing apparent disease, but colonization in immunocompromised hosts may result in a potentially fatal pneumonia known as Pneumocystis pneumonia. Although Pneumocystis are fungi, this genus has characteristics that make it atypical among other fungi. Pneumocystis do not appear to synthesize the major fungal sterol, ergosterol, and biochemical analyses have shown that they utilize cholesterol rather than ergosterol as the bulk sterol. Pneumocystis carinii appears to scavenge exogenous sterols, including cholesterol, from its mammalian host. As a result, it has long been held that their ability to scavenge cholesterol from their hosts, and their inability to undergo sterol biosynthesis, makes them resistant to antifungal drugs that target ergosterol or ergosterol biosynthesis. However, genome scans and in vitro assays indicate the presence of sterol biosynthetic genes within the P. carinii genome, and targeted inhibition of these enzymes resulted in reduced viability of P. carinii, suggesting that these enzymes are functional within the organism. Heterologous expression of P. carinii sterol genes, along with biochemical analyses of the lipid content of P. carinii cellular membranes, have provided an insight into sterol biosynthesis and the sterol-scavenging mechanisms used by these fungi.
- Creator/Author:
- Grant, Tiffany
- Submitter:
- Tiffany Grant
- Date Uploaded:
- 04/14/2016
- Date Modified:
- 04/14/2016
- License:
- All rights reserved
-
- Type:
- Document
- Description/Abstract:
- Fungi in the genus Pneumocystis are the cause of a potentially life threatening pneumonia, Pneumocystis pneumonia (PCP). The understanding of the lifecycle, metabolism, and drug development has been hindered due to a lack of a long term in vitro culture system. Unlike most other fungi, members of the genus Pneumocystis do not appear to synthesize the major fungal sterol, ergosterol. However, genome scans and in vitro assays suggest the presence of functional genes involved in a sterol pathway. One of the goals of this work was to characterize the P. carinii sterol enzyme, lanosterol synthase (Erg7p), an essential enzyme of the sterol pathway. The activity of P. carinii Erg7p was assessed by heterologous expression of P. carinii Erg7p in a Saccharomyces cerevisiae Erg7p null mutant. Growth rates and lanosterol production were similar between S. cerevisiae expressing the P. carinii enzyme and S. cerevisiae expressing its own Erg7p under the same conditions, indicating that not only does P. carinii produce a functional Erg7p, but also that the enzyme functionally complements the S. cerevisiae enzyme. Western blotting and fluorescent localization studies revealed that P. carinii Erg7p localizes to lipid particles in S. cerevisiae as does S. cerevisiae Erg7p. A novel finding of these studies, was that P. carinii contains lipid particles, and that P. carinii Erg7p localizes to lipid particles in P. carinii. These studies indicate that P. carinii Erg7p functions similar to the S. cerevisiae enzyme, and may perform a similar function in P. carinii. Biochemical analyses of sterols within the membranes of P. carinii have shown that it utilizes cholesterol rather than ergosterol as its bulk sterol. However, P. carinii does not appear to synthesize cholesterol from a de novo pathway, but rather scavenges exogenous sterols from its mammalian host. S. cerevisiae is induced to undergo sterol scavenging under anaerobic conditions. Consequently, another goal of this work was to provide information on the effect of O2 on sterol biosynthesis and sterol scavenging by P. carinii. ATP measurements revealed that the viability of P. carinii is severely decreased when maintained under hypoxic conditions, and this decrease correlated with an increase in drug susceptibility. We show that uptake of exogenous cholesterol by P. carinii occurred under normal O2 tensions, indicating that sterol scavenging is not limited to anaerobic conditions. Microarray analysis indicated that hypoxic maintenance of P. carinii resulted in decreased transcription of several genes involved in sterol and lipid biosynthesis suggesting that while hypoxic conditions down-regulated genes involved in sterol biosynthesis, down-regulation of sterol biosynthesis is not a requirement for sterol scavenging in P. carinii. The ability of P. carinii to scavenge exogenous sterols under normal O2 tensions at which the sterol pathway is unaffected provides evidence that sterol scavenging may be the primary means that P. carinii utilizes to obtain its sterols.
- Creator/Author:
- Grant, Tiffany
- Submitter:
- Tiffany Grant
- Date Uploaded:
- 04/14/2016
- Date Modified:
- 08/09/2016
- License:
- All rights reserved
-
- Type:
- Article
- Description/Abstract:
- Hyperelastic constitutive models of soft tissue mechanical behavior are extensively used in applications like computer-aided surgery, injury modeling, etc. While numerous constitutive models have been proposed in the literature, an objective method is needed to select a parsimonious model that represents the experimental data well and has good predictive capability. This is an important problem given the large variability in the data inherent to soft tissue mechanical testing. In this work, we discuss a Bayesian approach to this problem based on Bayes factors. We propose a holistic framework for model selection, wherein we consider four different factors to reliably choose a parsimonious model from the candidate set of models. These are the qualitative fit of the model to the experimental data, evidence values, maximum likelihood values, and the landscape of the likelihood function. We consider three hyperelastic constitutive models that are widely used in soft tissue mechanics: Mooney-Rivlin, Ogden and exponential. Three sets of mechanical testing data from the literature for agarose hydrogel, bovine liver tissue, porcine brain tissue are used to calculate the model selection statistics. A nested sampling approach is used to evaluate the evidence integrals. In our results, we highlight the robustness of the proposed Bayesian approach to model selection compared to the likelihood ratio, and discuss the use of the four factors to draw a complete picture of the model selection problem.
- Creator/Author:
- Madireddy, Sandeep; Vemaganti, Kumar, and Sista, Bhargava
- Submitter:
- Kumar Vemaganti
- Date Uploaded:
- 01/21/2015
- Date Modified:
- 05/23/2019
- Date Created:
- 2015-01-21
- License:
- All rights reserved
-
Reading and Writing as Scientists? Text Genres and Literacy Practices in Girls' Middle-Grade Science
- Type:
- Article
- Description/Abstract:
- Science teachers are often charged with providing discipline-specific literacy instruction. However, little is known about the reading and writing genres, or text types, typically found in these classrooms. In particular, there is a lack of knowledge about what opportunities adolescents have to engage with the genres privileged in science to learn the discipline's specialized ways of making meaning and communicating knowledge. This article reports on a case study of the reading and writing genres found within four middle-grade science classrooms in one small all-female school. Results suggest that although a variety of text genres were present, there was little discussion of how and why science content was presented in particular ways. Notably, students also had far more opportunities to read than write extended nonfiction. Teachers can cultivate a more reciprocal relation between reading and writing in science by using genres that students read as models for their writing.
- Creator/Author:
- Faller, S. Elisabeth (Beth)
- Submitter:
- S. Elisabeth (Beth) Faller
- Date Uploaded:
- 09/11/2017
- Date Modified:
- 07/03/2018
- Date Created:
- License:
- All rights reserved
-
- Type:
- Document
- Description/Abstract:
- With the several changes happening every day in societies and in thoughts say knowledge challenges are increasing day by day which is to be faced by business as well as other organizations. To tackle these challenges many tactics are implemented and are in process to further improve. Handling of these challenges requires a system under which one can work and let adaptation to the changes can be done smoothly. Today majority of business organizations have a knowledge management program in one or another form. Indian business organizations are also feeling the need for new business paradigms. Knowledge management is a systematic process for creating, acquiring, synthesizing, learning, sharing and using knowledge and experience to achieve organizational goals. This paper “Handling Knowledge in Indian Information Technology (IT) Organizations” underscores Knowledge Management practices in business organizations at main cities in India. Papers site an overview of the techniques and also include future improvements that can be done to ameliorate the efficiency of Knowledge Management System.
- Creator/Author:
- Ajmera, Himanshu; Agarwal, Ratish, and Pawar, Mahesh
- Submitter:
- Himanshu Ajmera
- Date Uploaded:
- 09/03/2017
- Date Modified:
- 05/23/2019
- Date Created:
- 2016-12-02
- License:
- All rights reserved
-
- Type:
- Article
- Description/Abstract:
- The alternative education field lacks a common definition and has a major divide between the differing philosophies of alternative programs; little empirical evidence is available to identify the components necessary to create effective alternative educational programs. Tremendous growth in the availability of alternative programs in the United States over the past several decades, however, illustrates continuing demand for such programs as well as the need for research on the characteristics that constitute effective alternative programs. In this article, the authors study exemplary alternative programs in 3 racially and economically diverse communities to characterize the school climate as viewed by the students and the staff. At this relatively early stage in the field of alternative education, it is essential to examine the similarities, as well as any differences, in the social climate of highly effective alternative programs and to consider their potential relationship with student academic and behavioral success. Furthermore, it is important to recognize how these findings might be one foundation for future inquiry and research on alternative education. [PUBLICATION ABSTRACT]
- Creator/Author:
- Tonelson, Steven W.; Magee Quinn, Mary; Gable, Robert A.; Faller, S. Elisabeth (Beth), and Poirier, Jeffery M.
- Submitter:
- S. Elisabeth (Beth) Faller
- Date Uploaded:
- 08/23/2017
- Date Modified:
- 08/23/2017
- License:
- All rights reserved
-
- Type:
- Document
- Description/Abstract:
- Teaching Case from the Public Education Leadership Project at Harvard University, A joint initiative of the Harvard Graduate School of Education and the Harvard Business School
- Creator/Author:
- Kim, John J-H; Faller, S. Elisabeth (Beth); Moore Johnson, Susan; Marietta, Geoff, and Noonan, James
- Submitter:
- S. Elisabeth (Beth) Faller
- Date Uploaded:
- 08/23/2017
- Date Modified:
- 10/02/2017
- License:
- All rights reserved
-
- Type:
- Document
- Description/Abstract:
- Teaching Case from the Public Education Leadership Project at Harvard University, A joint initiative of the Harvard Graduate School of Education and the Harvard Business School
- Creator/Author:
- Marietta, Geoff; Faller, S. Elisabeth (Beth); Moore Johnson, Susan, and Grossman, Allen
- Submitter:
- S. Elisabeth (Beth) Faller
- Date Uploaded:
- 08/23/2017
- Date Modified:
- 10/02/2017
- License:
- All rights reserved
-
- Type:
- Article
- Description/Abstract:
- The present study aims to advance the extant research base by evaluating the implementation and effectiveness of an academic vocabulary program designed for use in mainstream middle school classrooms with high proportions of language minority learners. The quasi-experimental, mixed-methods study was conducted in 21 classes (13 treatment matched to 8 control) in seven middle schools in a large district, with 476 sixth-grade students (346 language minority learners, 130 native English speakers). Classroom observations and teacher logs indicated the 18-week program was implemented with good fidelity and that the approach contrasted sharply with the standard district English language arts (ELA) curriculum. Multilevel modeling indicated that the program resulted in significant effects on several aspects of vocabulary knowledge, including meanings of taught words (d = 0.39; p < .0001), morphological awareness (d = 0.20; p = .0003), and the word meanings as presented in expository text (d = 0.20; p = .0227). The program also yielded marginally significant, but promising effects on a depth of word knowledge measure (d = 0.15; p =0.0830) and a norm-referenced measure of reading comprehension (d = 0.15; p = .0568). No effects were found on a norm-referenced vocabulary measure. These effects were comparable for language minority learners and their native-English-speaking classmates. Data from teachers shed light on the challenges of meeting students' diverse instructional needs and the roles of curriculum and professional networks in building instructional capacity. The findings show promise in developing effective multifaceted vocabulary instruction for implementation by ELA teachers in middle school classrooms with high numbers of language minority learners.
- Creator/Author:
- Lesaux, Nonie K.; Kelley, Joan G.; Faller, S. Elisabeth (Beth), and Kieffer, Michael J.
- Submitter:
- S. Elisabeth (Beth) Faller
- Date Uploaded:
- 08/23/2017
- Date Modified:
- 10/02/2017
- License:
- All rights reserved