First Steps towards Underdominant Genetic Transformation of Insect Populations

The idea of introducing genetic modifications into wild populations of insects to stop them from spreading diseases is more than 40 years old. Synthetic disease refractory genes have been successfully generated for mosquito vectors of dengue fever and human malaria. Equally important is the development of population transformation systems to drive and maintain disease refractory genes at high frequency in populations. We demonstrate an underdominant population transformation system in Drosophila melanogaster that has the property of being both spatially self-limiting and reversible to the original genetic state. Both population transformation and its reversal can be largely achieved within as few as 5 generations. The described genetic construct {Ud} is composed of two genes; (1) a UAS-RpL14.dsRNA targeting RNAi to a haploinsufficient gene RpL14 and (2) an RNAi insensitive RpL14 rescue. In this proof-of-principle system the UAS-RpL14.dsRNA knock-down gene is placed under the control of an Actin5c-GAL4 driver located on a different chromosome to the {Ud} insert. This configuration would not be effective in wild populations without incorporating the Actin5c-GAL4 driver as part of the {Ud} construct (or replacing the UAS promoter with an appropriate direct promoter). It is however anticipated that the approach that underlies this underdominant system could potentially be applied to a number of species. Figure

Rituximab therapy in pulmonary alveolar proteinosis improves alveolar macrophage lipid homeostasis

Rationale Pulmonary Alveolar Proteinosis (PAP) patients exhibit an acquired deficiency of biologically active granulocyte-macrophage colony stimulating factor (GM-CSF) attributable to GM-CSF specific autoantibodies. PAP alveolar macrophages are foamy, lipid-filled cells with impaired surfactant clearance and markedly reduced expression of the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) and the PPARγ-regulated ATP binding cassette (ABC) lipid transporter, ABCG1. An open label proof of concept Phase II clinical trial was conducted in PAP patients using rituximab, a chimeric murine-human monoclonal antibody directed against B lymphocyte specific antigen CD20. Rituximab treatment decreased anti-GM-CSF antibody levels in bronchoalveolar lavage (BAL) fluid, and 7/9 patients completing the trial demonstrated clinical improvement as measured by arterial blood oxygenation. Objectives This study sought to determine whether rituximab therapy would restore lipid metabolism in PAP alveolar macrophages. Methods BAL samples were collected from patients pre- and 6-months post-rituximab infusion for evaluation of mRNA and lipid changes. Results Mean PPARγ and ABCG1 mRNA expression increased 2.8 and 5.3-fold respectively (p ≤ 0.05) after treatment. Lysosomal phospholipase A2 (LPLA2) (a key enzyme in surfactant degradation) mRNA expression was severely deficient in PAP patients pre-treatment but increased 2.8-fold post-treatment. In supplemental animal studies, LPLA2 deficiency was verified in GM-CSF KO mice but was not present in macrophage-specific PPARγ KO mice compared to wild-type controls. Oil Red O intensity of PAP alveolar macrophages decreased after treatment, indicating reduced intracellular lipid while extracellular free cholesterol increased in BAL fluid. Furthermore, total protein and Surfactant protein A were significantly decreased in the BAL fluid post therapy. Conclusions Reduction in GM-CSF autoantibodies by rituximab therapy improves alveolar macrophage lipid metabolism by increasing lipid transport and surfactant catabolism. Mechanisms may involve GM-CSF stimulation of alveolar macrophage ABCG1 and LPLA2 activities by distinct pathways

Extracellular Hsp72 concentration relates to a minimum endogenous criteria during acute exercise-heat exposure

Extracellular heat-shock protein 72 (eHsp72) concentration increases during exercise-heat stress when conditions elicit physiological strain. Differences in severity of environmental and exercise stimuli have elicited varied response to stress. The present study aimed to quantify the extent of increased eHsp72 with increased exogenous heat stress, and determine related endogenous markers of strain in an exercise-heat model. Ten males cycled for 90 min at 50% O2peak in three conditions (TEMP, 20°C/63% RH; HOT, 30.2°C/51%RH; VHOT, 40.0°C/37%RH). Plasma was analysed for eHsp72 pre, immediately post and 24-h post each trial utilising a commercially available ELISA. Increased eHsp72 concentration was observed post VHOT trial (+172.4%) (P<0.05), but not TEMP (-1.9%) or HOT (+25.7%) conditions. eHsp72 returned to baseline values within 24hrs in all conditions. Changes were observed in rectal temperature (Trec), rate of Trec increase, area under the curve for Trec of 38.5°C and 39.0°C, duration Trec ≥ 38.5°C and ≥ 39.0°C, and change in muscle temperature, between VHOT, and TEMP and HOT, but not between TEMP and HOT. Each condition also elicited significantly increasing physiological strain, described by sweat rate, heart rate, physiological strain index, rating of perceived exertion and thermal sensation. Stepwise multiple regression reported rate of Trec increase and change in Trec to be predictors of increased eHsp72 concentration. Data suggests eHsp72 concentration increases once systemic temperature and sympathetic activity exceeds a minimum endogenous criteria elicited during VHOT conditions and is likely to be modulated by large, rapid changes in core temperature

Reinvisioning the Nineteenth Century in Cherie Priest’s Boneshaker : Gender, Ethnicity, and Class

Cherie Priest’s Boneshaker, an alternate history novel, examines the cultural and political atmosphere in late nineteenth-century America. It focuses on a group of women marginalized from mainstream society because of their race, culture, or class. The novel’s heroine, Briar, a poor working woman, is rejected by society and suffers labor exploitation. In response to her oppressive circumstances, she joins a community of women, and together, they rebel against an oppressive, patriarchal society. My paper explores Priest’s adaptation of the social, historical, and cultural background of the nineteenth-century and the treatment of gender, ethnicity, and class through her characters. Boneshaker examines nineteenth-century standards of motherhood and marriage. I argue that it disrupts the extreme codes that define motherhood and marriage because its women are not defined by their status as wives and Briar creates her own conventions for parenting as a single mother. They are not restricted by conventional, middle class nineteenth-century values regarding marriage and motherhood. I argue that as an alternate history fiction, Boneshaker has the ability to liberate and empower those disenfranchised by race, class, or gender. While Priest succeeds in freeing her female characters from oppressive nineteenth-century gender constraints, she does not respond to anti-Chinese sentiment. Boneshaker offers a historically accurate portrayal of Chinese racism in the nineteenth-century, but it refuses to effectively confront it in the same way it does for gender oppression and Native American racism. The women in Boneshaker are offered gender liberation, and the Native American woman, while she suffers from racist attitudes, is given the power to defend herself from her attackers. Boneshaker’s Chinese reflect nineteenth-century depictions that stereotype them as submissive and passive. In Boneshaker, they are effectively silenced through language barriers or disability, and are never given the opportunity to respond to racism. They continually suffer abuse at the hands of white male characters, but are never given the opportunity to defend themselves. I argue that Boneshaker’s treatment of the Native American princess Angeline is in response to nineteenth-century stereotypes of Native women. Priest refuses to reduce Angeline to stereotypes that liken her to middle class white women. In many nineteenth-century periodicals and literature, Native women were written to appeal to the middle class sensibility of white women readers. To achieve this, the depiction of Native women reflected the white middle class woman in looks and values. The role of the Native woman in popular nineteenth-century fiction was typically reduced to the romantic interest of a white man or she was depicted as the noble savage, willing to deceive her people to save white men. I argue that Boneshaker’s depiction of Princess Angeline as an independent, rebellious, liberated woman, offers readers a historically accurate portrayal of the Native American woman. The alternate history novel offers Boneshaker the ability to reimagine and reinvision the nineteenth-century; however, it does not always take advantage of its genre possibilities. Boneshaker is an example of the limitations and advantages of the genre in its inability to significantly respond to Chinese racism while also demonstrating class and gender liberation. Boneshaker offers women an alternate space in which they are given autonomy and act as active agents in the construction of history

Personality types and value orientations with special reference to the feminine role

The problem of conflict in the feminine role is the result of social and cultural changes of the past several decades. The traditional middle and upper class feminine role expectations were focused upon marriage and the family and the woman's interests, values, and actions were expected to be channeled in the direction of obligation to the family group. The woman's individual needs and interests were expected to be subordinated to the needs and interests of her family. Society left little or no opportunity for the woman of the colonial period to play any role other than this one, so closely connected with her biological role of bearing children. The woman who did not marry was forced to choose between becoming a member of a relative's family as the stereotyped "maiden aunt" and becoming a governess or teacher. The opportunity for individual achievement in this latter role was highly limited

A rhetorical analysis of logos, pathos, and ethos in selected speeches of Terry Sanford

On February 4, 1960, Terry Sanford announced his candidacy for the governorship of North Carolina. This step, the result of fourteen years of strategic career planning, brought Sanford into regional prominence and gave him the opportunity to enunciate the ambitious educational plan with which he has been consistently associated. His successful bid for governor was followed by a vigorous campaign on behalf of the first major legislation of his administration, the B Budget Request. The passage of this budget request assured the implementation of that progressive educational program outlined in his campaign for governor. Most of Sanford's accomplishments are embodied in the B Budget Request. This study focuses on the B Budget Request campaign and specifically on six selected speeches that are representative of Sanford's style and strategy. The study applies Aristotelian principles of artistic proof, i.e., logos, pathos and ethos, to the six selected speeches of Terry Sanford

Leadership styles and teacher involvement in the decision-making process in the small administrative unit

Many traditional models of the managerial process in public school organizations have been autocratic or bureaucratic in nature. The manager makes decisions on matters within his particular area of freedom, issues the directives and orders to his subordinates, and monitors their performance to ensure conformity with the decisions made and the directives issued. In too many instances, administrators have not involved the faculty and staff in the decision-making process. Public schools must develop mechanisms for decision-making that will build trust rather than diminish it, and these mechanisms must involve the willingness to delegate authority and to allow individuals to assume leadership. The key to this process is to develop the proper framework for the decision-making process and to determine the level of teacher involvement which will be most effective. The efforts behind the decision-making process, the implementation of the decision made, and the responsibility for the decisions can be shared. If all who are involved in the sharing process have productive input and cooperative planning is provided, then an effective decision-making mechanism can be established within the school system

The legal aspects of religion in the public school curriculum

The role of religion in the public schools is one of the most controversial issues in American education. The vast number of religious groups and their widely differing opinions contribute to the controversy. In addition, few topics stir human emotions more strongly than the mention of religious activities in the public schools. School officials face challenges in trying to follow the laws of the land, accommodate local religious customs, protect the rights of minority groups, and deal with their own religious beliefs. The purposes of this study were (1) to review the history of religion in the public school curriculum; (2) to determine from current literature the critical legal issues involving religion in the public school curriculum; (3) to review and analyze case law related to religion in the public school curriculum; and (4) to provide guidelines for practicing school administrators who must make decisions on the legality of permitting religious activities as part of the public school curriculum. This study is developed in a factual manner based on the legal issues involved and will not attempt to address the moral values inherent in permitting religious activities in the public school curriculum