Manipulation of second messengers by ectopic expression of receptors in transgenic Drosophila

The combination of physiology and genetics affords opportunities to perform experiments with greater precision, and with less risk of artefact, than heretofore possible. This is illustrated here by demonstrating the selective manipulation of the second messengers cyclic GMP (cGMP), cyclic AMP (cAMP) and calcium (Ca2+) in the renal (Malpighian) tubule of the genetic model organism, Drosophila melanogaster. The importance of the second messengers cGMP, cAMP and Ca2+ in control of fluid transport makes the Malpighian tubule an ideal testbed for such technology. The actions of known hormones can be compared with the results obtained by manipulating levels of the second messenger through which these are thought to act. Flies were constructed or obtained transgenic for the rat atrial natriuretic peptide receptor, GC-A, the Drosophila 5HT7Dro receptor, and the Drosophila 5HT1ADro receptor, under control of the UAS or heat-shock promoter. Tubules dissected from such flies were then demonstrated to show diuresis induced by application of rANP or 5HT, whereas controls showed no response. Second messenger measurements showed that the rat GC-A receptor acted to raise cGMP levels, the 5HT7Dro receptor to raise cAMP levels, and the 5HT1ADro receptor to raise intracellular calcium. In addition, modulation of both cell-specific cell nucleotide phosphodiesterase activity and cell-specific cyclic nucleotide-dependent kinase activity of tubules with elevated cyclic nucleotide levels was observed, implicating these enzymes as key regulators/effectors of signalling in tubules. Cross-talk between cGMP, cAMP and Ca2+ was also assessed and shown to be variable, depending on the particular cell type in which the signal was generated. This reveals further complexity in the control of tubules and suggests a distinct role for cyclic nucleotide-gated channels in principal cells. This study has validated ectopic transgene expression as a generic technology with potential beyond Malpighian tubules: in principle, such transgenes can be expressed specifically in any population of cells that can be delineated by a GAL4 driver line

The effects of lysophospholipids and oxidised low-density lipoproteins on the L-arginine: Nitric oxide pathways in isolated rabbit and rat aorta

Elevated plasma levels of low-density lipoproteins (LDL) are a major risk factor for the development of atherosclerosis. Atherosclerotic vessels from humans and animals show impaired endothelium-dependent relaxations (EDR) and altered responses to contractile agonists. Recent evidence suggests that oxidation of LDL is a key process in atherogenesis and plays an important role in the alterations in vascular reactivity. This study investigated the effects of a major component of oxidised LDL (OXLDL), lysophosphatidylcholine (LPC), on vascular responses in isolated rabbit and rat aortic rings. In addition, the effects of OXLDL on EDR in rat aortic rings was also examined. Furthermore, the possibility that impaired EDR in atherosclerotic vessels could be restored by L-arginine was investigated. LPC caused immediate, dose dependent and partially reversible inhibition of EDR evoked by ACh, ATP and A23187 in rabbit aortic rings. This inhibition was decreased by serum albumin but not by L-arginine or indomethacin. Relaxations to exogenous NO and glyceryl trinitrate in endothelium-denuded tissues were unaffected by LPC, but responses were inhibited in endothelium-intact rings suggesting the release of an inhibitory factor from the endothelium. LPC also evokes EDR which are mediated by the release of NO. This dual effect of LPC can be demonstrated in the same tissue. Contractile responses to phenylephrine (PE) and 5-HT were unaffected in denuded tissues, but were inhibited in endothelium-intact tissues, again suggesting the release of a factor from the endothelium. Relaxations evoked by L-arginine in isolated rat aortic rings were mediated by an inducible nitric oxide synthase (NOS). At a concentration that inhibited relaxations elicited by ACh, OXLDL did not influence L-arginine-evoked relaxations, whereas LPC potentiated responses. NOS activity induced in vivo by endotoxin injection, was studied ex vivo by observation of PE-evoked contractions. Contractions were attenuated in rings from endotoxin-treated rats. However, the effect of this treatment was unaffected by the presence of OXLDL or LPC. Aortic rings from WHHL rabbits which spontaneously develop atherosclerosis, showed impaired EDR. This impairment was not influenced by incubation of the tissues with L-arginine. Furthermore, rabbits fed a diet supplemented with L-arginine did not show improved endothelium- dependent responses in vitro. In addition, L-arginine feeding did not influence contractile responses to PE. In conclusion, LPC can modulate EDR and contractile responses in isolated tissues although, these effects do not mimic those reported for OXLDL. In contrast, OXLDL and LPC do not inhibit the activity of an inducible form of NOS. Finally, the impairment of EDR observed in atherosclerotic vessels cannot be reversed by the administration of L-arginine

India: Domestic Issues, Strategic Dynamics, and U.S. Relations

[Excerpt] President Barack Obama’s Administration has sought to build upon the deepened U.S. engagement with India begun by President Bill Clinton in 2000 and expanded upon during much of the past decade under President G.W. Bush. This “U.S.-India 3.0” diplomacy was most recently on display in July 2011, when the second U.S.-India Strategic Dialogue session saw a large delegation of senior U.S. officials visit New Delhi to discuss a broad range of global and bilateral issues. Many analysts view the U.S.-India relationship as being among the world’s most important in coming decades and see potentially large benefits to be accrued through engagement on many convergent interests. Bilateral initiatives are underway in all areas, although independent analysts in both countries worry that the partnership has lost momentum in recent years. Outstanding areas of bilateral friction include obstacles to bilateral trade and investment, including in the high-technology sector; outsourcing; the status of conflict in Afghanistan; climate change; and stalled efforts to initiate civil nuclear cooperation. India is the world’s most populous democracy and remains firmly committed to representative government and rule of law. Its left-leaning Congress Party-led ruling national coalition has been in power for more than seven years under the leadership of Prime Minister Manmohan Singh, an Oxford-trained economist. New Delhi’s engagement with regional and other states is extensive and reflects its rising geopolitical status. The national economy has been growing rapidly—India’s is projected to be the world’s third-largest economy in the foreseeable future—yet poor infrastructure, booming energy demand, and restrictive trade and investment practices are seen to hamper full economic potential. Despite the growth of a large urban middle-class, India’s remains a largely rural and agriculture-based society, and is home to some 500-600 million people living in poverty. This report will be updated periodically

A Post-intentional Phenomenological Study of a Queer Identified Youth in Jamaica

The paper provides an exploration of glimpses into the life of a Jamaican woman who loves women The research question this paper examines is how societal homonegativity shapes the lived experiences of a young woman who loves women in Jamaica Post-intentional phenomenology methodology was used to capture salient moments of the woman s life through written memory song lyrics and artifacts Results suggested that fear hope care and being perceived as diseased are a daily part of a woman who loves women s life There is a need to tell the stories of women who love in Jamaica to validate their lived experiences and to construct a body of knowledge on this topic Implications for this study can be used to mobilize education research community and support for students with female same-sex caregiver

Mentoring Uncertified Teachers in Guyana

In 2022 Guyana s Ministry of Education began a teacher licensing system highlighting the need for continuous development Teacher quality is a challenge in many developing countries The research question that guided this study was how does a customized professional development intensive mentoring program influence the preparation of uncertified teachers in Guyana as it relates to their lack of pedagogical content knowledge and classroom management skills Data were collected and analyzed using the Delphi Technique a group decision-making method to reach a consensus that identified what a customized professional development solution for uncertified teachers in two high schools in Guyana entailed specifically an intensive mentoring intervention Results from this study showed that a customized professional development intensive mentoring training program could be beneficial for uncertified teachers in Guyana The findings implied the presence of collaboration support and collegially sharing ideas and strategies that address evidence-based teaching practice

Letters between Lora Martin and W. J. Kerr

Letters concerning a position in the shorthand department at Utah Agricultural College

Descriptive research into large-scale user data from an established alcohol identification and brief advice (IBA) intervention website

© 2024 The Author(s). Published online on figshare. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0Alcohol misuse causes significant health harms, including early mortality, increased healthcare and wider governmental costs. Identification and Brief Advice (IBA) interventions can reduce alcohol consumption, prevent alcohol misuse disorder progression, and are cheaper to deliver digitally than in-person. However, high-quality evidence is lacking for delivering IBA interventions, at scale, via publicly available websites. This study uses descriptive data from individuals in the United Kingdom (UK) and some from other countries over a six-year period from DrinkCoach, a website which delivers an IBA intervention developed in the UK delivering tailored interventions based on users’ Alcohol Use Disorders Identification Test (AUDIT) scores. Researchers employed descriptive statistics, double-tailed Z tests and X2 tests for relationships between variables. In 2018, 60,745 IBA interventions were completed, with 86% of these recording AUDIT scores > 7, indicating risky drinking. Significant positive relationships were identified between the AUDIT score and users’ demographics such as gender and age-group which are well-established as well as new insights into relationships between AUDIT score and the time of the year or day the interventions were accessed and delivered, as well as the follow-up options selected by users. The website attracted a disproportionately higher proportion of risky drinkers completing IBA interventions compared with prevalence estimates or identified through in-person IBA approaches in the UK. The research indicates that websites delivering IBA interventions may support help-seeking behaviour for risky drinkers by providing anonymity and low interaction costs. The research results demonstrated a significant cost-benefit at scale when compared to in-person, particularly in specific local authorities who paid to access website data about their populations. This cost-benefit approach should inform alcohol health funding decisions and warrant further, higher-quality research into outcomes from websites delivering IBA interventions