Institutional Funding Research Articles

Agricultural Innovation and Food Security in Sub-Saharan Africa in Nigeria

Purpose: The aim of the study was to analyze the agricultural innovation and food security in Sub-Saharan Africa in Nigeria. Methodology: This study adopted a desk methodology. A desk study research design is commonly known as secondary data collection. This is basically collecting data from existing resources preferably because of its low cost advantage as compared to a field research. Our current study looked into already published studies and reports as the data was easily accessed through online journals and libraries. Findings: In Nigeria, agricultural innovation is vital for improving food security. Research suggests that adopting innovative farming methods and technologies can boost productivity, resilience to climate change, and livelihoods for smallholder farmers. Overcoming challenges like limited access to finance and inadequate infrastructure is essential to fully harnessing the benefits of agricultural innovation for food security in Nigeria. Unique Contribution to Theory, Practice and Policy: Diffusion of innovations theory, social capital theory & political economy theory may be used to anchor future studies on agricultural innovation and food security in Sub-Saharan Africa in Nigeria. Promote farmer-centered innovation platforms - establishing can facilitate knowledge sharing, collaboration, and co-creation of agricultural innovations. Adequate funding for research institutions, agricultural universities, and extension agencies is essential to conduct applied research, develop appropriate technologies, and provide technical assistance to farmers.

Intranasal SARS-CoV-2 Omicron variant vaccines elicit humoral and cellular mucosal immunity in female mice

In order to prevent the emergence and spread of future variants of concern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), developing vaccines capable of stopping transmission is crucial. The SARS-CoV-2 vaccine NDV-HXP-S can be administered live intranasally (IN) and thus induce protective immunity in the upper respiratory tract. The vaccine is based on Newcastle disease virus (NDV) expressing a stabilised SARS-CoV-2 spike protein. NDV-HXP-S can be produced as influenza virus vaccine at low cost in embryonated chicken eggs. The NDV-HXP-S vaccine was genetically engineered to match the Omicron variants of concern (VOC) BA.1 and BA.5 and tested as an IN two or three dose vaccination regimen in female mice. Furthermore, female mice intramuscularly (IM) vaccinated with mRNA-lipid nanoparticles (LNPs) were IN boosted with NDV-HXP-S. Systemic humoral immunity, memory T cell responses in the lungs and spleens as well as immunoglobulin A (IgA) responses in distinct mucosal tissues were characterised. NDV-HXP-S Omicron variant vaccines elicited high mucosal IgA and serum IgG titers against respective SARS-CoV-2 VOC in female mice following IN administration and protected against challenge from matched variants. Additionally, antigen-specific memory B cells and local T cell responses in the lungs were induced. Host immunity against the NDV vector did not interfere with boosting. Intramuscular vaccination with mRNA-LNPs was enhanced by IN NDV-HXP-S boosting resulting in improvement of serum neutralization titers and induction of mucosal immunity. We demonstrate that NDV-HXP-S Omicron variant vaccines utilised for primary immunizations or boosting efficiently elicit humoral and cellular immunity. The described induction of systemic and mucosal immunity has the potential to reduce infection and transmission. This work was partially funded by the NIAIDCenters of Excellence for Influenza Research and Response (CEIRR) and by the NIAID Collaborative Vaccine Innovation Centers and by institutional funding from the Icahn School of Medicine at Mount Sinai. See under Acknowledgements for details.

Adoption of Accounting Information System and Financial Accountability in TVET Institutions in Eastern Region Kenya

The purpose of the study was to determine the effect of adoption of accounting information system on financial accountability in TVET institutions in Eastern Region Kenya. The target population was 69 participants, encompassing principals, Board of Governors (BOG) chairs, and finance officers from 23 TVET institutions within the Eastern Region. Census method was adopted and a mixed-method approach using a descriptive design was employed in this research. Questionnaires were used to collect primary data while scrutinizing audited financial statements to amass secondary data. The data was processed through a blend of descriptive and inferential statistical methods presented using tables and explanations. The questionnaire findings indicated that 24(41%) respondents strongly agreed and 11(19%) agreed that the adoption of an AIS had facilitated timely financial reporting in my institution (mean of 4.16). Additionally, 12(21%) respondents strongly agreed and 17(29%) agreed that implementing an AIS had augmented the efficiency of financial processes and data capturing in our institution (mean of 3.70). Further, 16(28%) respondents strongly agreed and 14(24%) agreed that an effective AIS improved the accountability of financial resources in the institution (mean of 3.67). The secondary results revealed that expenses had a mean of 4.21 and as well as debtors had a mean of 4.35. Nevertheless, the net profit had a low mean of 2.74. The Pearson correlation coefficient r=0.151** at α < 0.019 and 99% significance level. On accounting information system, the study concluded that there was a significant effect of adoption of accounting information systems on financial accountability in TVET institutions in the Eastern region of Kenya. It was noted that the implementation of AIS had enabled most TVETs to report their financial standings on time due to efficient processing of information when inputted accurately. Therefore, it was considered an enhancer towards financial accountability in regards to the proper utilization of TVETs’ institution. The study thus recommends that TVET management should provide more funding to strengthen the current accounting information systems from cyber-attacks. This will reduce malware attacks and siphoning of institutional funds to facilitate more efficient on bookkeeping and reporting, which are a function of ensuring financial accountability.

An exergy-based analysis of the effects of public incentives on the so-called “energy efficiency” of the residential sector, with emphasis on primary resource use and economics of scale

Improving building efficiency is essential for reducing energy consumption, greenhouse gas emissions, and operational costs. In OECD Countries the average share of the Residential and Commercial Sector for space conditioning accounts for 30–37% of the cumulative final energy use. The current situation is somewhat typical of post-industrialized Countries: while the technology for reducing the external thermal losses and for installing more energy-conscious devices and procedures (including real-time monitoring and better design of the enclosures) is readily available, the cost of such measures is often perceived as excessive for the private user. For this reason, some governments have resolved to launch incentivization campaigns to encourage both private and public actors to invest in building efficiency. This strategy has been successful and its large-scale application -even if enacted on a preliminary basis- led to substantial reductions of the energy load per square meter −50 to 100 kWh/(m2yr)- so that subsidies and incentives are likely to assume a major role in shaping the energy conversion market. Technologies that are deemed “more environmental benign” or “of strategic interest” will receive institutional funding to promote their implementation, the funds being allocated both to design techniques, new materials and less energivorous devices. Since the funding is usually provided in the form of tax rebates, this approach is not devoid of problems: in fact, previous campaigns at regional and national level in the primary Energy Conversion and in the Transportation Sector have resulted in monumental failures. While it is clearly in the interest of a community to enact a reduction of their final energy uses, it is also true that such incentivization plans, if not properly and carefully implemented, may constitute an economic and ecological “doping” of the market (detail price increases, material and components shortages, etc.). This paper is a follow-up of a previous study conducted in 2021–22 that proposed a rational and thermodynamic-based approach to the issue: in that paper we presented an innovative cost/benefit procedure that considers the primary exergy savings of an “energy saving” intervention and the installation/operation costs and combines them with the statistically foreseeable savings in the improvement of the building seismic class. The method is intended to serve as a possible model for future policy decisions, and it makes use of the fundamental principles of Exergy Analysis augmented by a conventional cost/benefit analysis and by basic resilience considerations. The case study analyzed in the previous paper is re-examined here in the light of some recent normative developments the Eco-Sisma-Bonus (“Superbonus”), the incentivization plan launched between 2014 and 2020 by the Italian Government.

Historical Portrait of the Yakut Merchant of the 1st Guild N. D. Everstov

The article is devoted to the study of the economic and social-educational activities of the Yakut merchant of the 1st guild N. D. Everstov. The main purpose of the publication is to reconstruct the historical portrait of N. D. Everstov. The article used the methodology of the civilizational approach formulated by A. Toynbee. The topic has theoretical and applied relevance. The author determined the origin of N. D. Everstov and the original sources of capital accumulation. In 1894, Everstov was the first Yakut to become a merchant of the 1st guild. In 1900, the trading house “N. D. Everstov” was founded in Yakutsk. In 1901, Everstov was awarded the title of commerce advisor and honorary citizen. The article reveals that Everstov organized a wholesale fur trade and an extensive network of agents in the 1860–1870s, entered the fairs of Irbit and Nizhny Novgorod, and had an annual turnover of 200–800 thousand rubles. In 1867–1878 at auctions in Leipzig they sold more than 50 lots of furs, with a total value of 865 thousand rubles. Dynamics of trade with China in 1865–1878 amounted to 50–100 thousand rubles annually, average profit 700 thousand rubles. N. D. Everstov laid the foundations for bill lending to entrepreneurs in North-Eastern Siberia. In 1860–1879, the lending rate was 12–13 % per annum, the total amount of loans was more than 145 thousand rubles. In 1910–1911, the merchant organized a bank with an authorized capital of 50 thousand rubles. A social and educational activity of N. D. Everstov was expressed in the financing of educational institutions, churches, missionary societies of Yakutsk. In 1915, the state of N. D. Everstov was estimated at 1 million rubles. Everstov’s sons continued their father’s trading and financial activities but were unable to create a large enterprise. The Yakut merchant laid the foundations for conducting trade and financial business with large capital in North-Eastern Siberia, organized the wholesale supply of consumer goods to the population of the region through the ports of the Sea of Okhotsk, and formed the trade and transport infrastructure of the macro-region.

Depicting oncologists' perceptions and knowledge of global disparities in conflicts of interest reporting: The ONCOTRUST-1 study.

9002 Background: Conflicts of interest (COI) between oncologists and the pharmaceutical industry might considerably influence how the presentation of the research results is delivered, impacting treatment decisions, and policy-making.While there are regulations on reporting COI in high-income countries (HICs), little is known about their reporting in low- and middle-income countries (LMICs).ONCOlogy TRansparency Under Scrutiny and Tracking (ONCOTRUST-1) is a pilot global survey to explore the knowledge and perceptions of oncologists regarding COI. Methods: We designed an online 27-question-based survey in English language to explore the perceptions and knowledge of oncologists regarding COI, with an emphasis on LMICs.Illustrative examples of COI were proposed, based on definitions from the American Society of Clinical Oncology (ASCO) and published literature. Descriptive statistics and the CROSS guidelines were used to report the findings. Results: ONCOTRUST-1 surveyed 200 oncologists, 70.9% of them practicing in LMICs. Median age of the respondents was 36 (range: 26-84) years; 47.5% of them were women. The median number of years of clinical practice was 9 (range: 1-51). 40.5% of respondents reported weekly visits by pharmaceutical representatives to their institutions. Regarding oncologists’ perceptions of COI that require disclosure, direct financial benefits, such as honoraria ranked highest (58.5%), followed by gifts from pharmaceutical representatives (50%) and support for attending conferences (44.5%). In contrast, personal or institutional research funding, sample drugs, consulting or advisory board, expert testimony, and food and beverage funded by pharmaceutical industry were less frequently considered as COI. Moreover, only 24% of surveyed oncologists could correctly categorize all situations representing a COI. Regarding support received from industry, 51.5% of respondents acknowledged trips to conferences as the most common form of support, followed by sample drugs (20.5%). Despite recognizing these interactions, 15% of respondents admitted feeling pressured to prescribe specific drugs due to their COI. Regarding COI reporting, a notable portion of participants indicated they report COI in their presentations (59%) or when publishing their research (30%). The presence of local regulations to manage COI were reported by 35.5% of respondents. The majority advocated for clearer policies and regulations (65%), training and education (63.5%), and an open COI database (55%) to improve COI reporting in oncology. Conclusions: These findings underscore the importance of clear guidelines, education, and transparency in reporting COI in oncology. This hypothesis-generating pilot survey provided the rationale for ONCOTRUST-2 study which will compare perceptions of COI among oncologists in LMICs and HICs.

Features of forming the enterprise’s balance according to international financial reporting standards

The formation of market relations and the aggravation of the economic situation in Ukraine require new approaches to enterprise management. The basis for decision-making on all issues of the company's activity is financial information necessary for a complete and comprehensive analysis of the state of its assets, liabilities and equity. The main source of information is financial reporting. The value of the balance sheet as the main reporting form cannot be overestimated, as it allows you to have an idea of the property and financial situation of the enterprise. The purpose of the paper is to research the peculiarities of the formation of the enterprise's balance sheet according to international standards. Also, the analysis of the formation of the balance sheet according to the National Accounting Regulations and in accordance with international standards. Therefore, the balance sheet is a system of indicators that characterizes the wide value ratio of the company's funds. The balance reflects the composition, placement, use and sources of funds of enterprises, organizations and budgetary institutions. The paper examines the peculiarities of forming a company's balance sheet in accordance with international standards. Specifically, it focuses on key aspects that define the process of preparing financial statements in accordance with international accounting standards. The authors explore the impact of international standards on balance sheet formation, including aspects such as asset and liability valuation, reporting on current assets, financial instruments, and more. It is noted that the adoption of international standards requires companies not only to comply with new rules but also to review and improve their internal processes and management systems. The study also highlights the advantages and challenges associated with the implementation of international standards in the practice of corporate accounting. The final recommendations of the paper emphasize the importance for companies to study and implement international standards in order to enhance their competitiveness and financial reporting transparency.

ADVANCED FOREIGN EXPERIENCES OF FINANCING HIGHER EDUCATION INSTITUTIONS

Progressed outside encounters of financing higher education institutions, higher education expenses of foreign universities, financing of higher education institutions of foreign countries from budget and extra-budgetary sources, encounters of the USA, Great Britain, Australia Canada and Kazakhstan as illustrations of the approach of fetched assignment, endowment funds of higher education institutions issues such as financing through budgetary assets were considered.

Separation Anxieties: A Comment on Weil’s Penalties for the Violation of Separation

Abstract Professor Weil’s thesis seems largely correct with respect to the United States, whose law on religious establishment I regularly teach. Funding is central to American debates over religious establishment. The fight over religious establishments in Virginia, which inspired both James Madison’s “Memorial and Remonstrance against Religious Assessments” and Thomas Jefferson’s “An Act for Establishing Religious Freedom,” was over whether persons could be forced to pay taxes to support religious instruction. Financial concerns were at the root of church-state debates in the nineteenth century, when Protestants repeatedly rebuffed Catholics who wanted funding for Catholic private schools. Many state constitutions still have what are known as mini-Blaine Amendments that forbid public funding for religious institutions. Whether proponents of a strong separation between church and state in the United States are fighting the same battles as proponents of a strong separation of church and state in France is nevertheless problematic. The French revolutionaries had to subordinate a reactionary church. The American revolutionaries merely had to negotiate peace treaties among the different sects that supported the Declaration of Independence. Separation of church and state in the United States is best conceptualized as a division of labor among liberal institutions rather than a means for purging anti-liberal religion from the liberal public sphere.

Nigeria's Climate Change Act 2021: A pathway to net-zero carbon emission, energy security and sustainability.

The global push for net-zero carbon emissions by 2050 requires countries to adopt sustainable energy sources, address energy poverty and promote energy security. Nigeria is grappling with an energy crisis, and the recently enacted Climate Change Act 2021 offers the prospect of addressing this while advancing energy sustainability. The study evaluates the Act's potential in promoting energy security and global net-zero carbon emissions. Nigeria faces challenges in recovering from the COVID-19 pandemic and combating climate change, prompting countries to take domestic and international measures to reduce greenhouse gas emissions. Through doctrinal legal research and conceptual analysis, the study examines Nigeria's Climate Change Act, proposing solutions to enhance its commitment to global net-zero carbon emissions. It conducts a comparative legal analysis of climate change frameworks in Kenya, Nigeria and the Democratic Republic of Congo, providing insights and suggesting reforms to Nigeria's Act for Energy Security. While the existing laws are adequate, weak enforcement by regulatory agencies and a lack of political will hinder compliance. Public awareness regarding individual contributions to climate change is also lacking. The study recommends increased funding for regulatory institutions and proactive public awareness. Complying with the Paris Agreement and Sustainable Development Goal 13 is vital for a sustainable energy future.

Do good: Strategies for leading an inclusive data science or statistics consulting team

Leading a data science or statistical consulting team in an academic environment can have many challenges, including institutional infrastructure, funding and technical expertise. Even in the most challenging environment, however, leading such a team with inclusive practices can be rewarding for the leader, the team members and collaborators. We describe nine leadership and management practices that are especially relevant to the dynamics of data science or statistics consulting teams and an academic environment: ensuring people get credit, making tacit knowledge explicit, establishing clear performance review processes, championing career development, empowering team members to work autonomously, learning from diverse experiences, supporting team members in navigating power dynamics, having difficult conversations and developing foundational management skills. Active engagement in these areas will help those who lead data science or statistics consulting groups – whether faculty or staff, regardless of title – create and support inclusive teams.

Getting your DUCs in a row - standardising the representation of Digital Use Conditions

Improving patient care and advancing scientific discovery requires responsible sharing of research data, healthcare records, biosamples, and biomedical resources that must also respect applicable use conditions. Defining a standard to structure and manage these use conditions is a complex and challenging task. This is exemplified by a near unlimited range of asset types, a high variability of applicable conditions, and differing applications at the individual or collective level. Furthermore, the specifics and granularity required are likely to vary depending on the ultimate contexts of use. All these factors confound alignment of institutional missions, funding objectives, regulatory and technical requirements to facilitate effective sharing. The presented work highlights the complexity and diversity of the problem, reviews the current state of the art, and emphasises the need for a flexible and adaptable approach. We propose Digital Use Conditions (DUC) as a framework that addresses these needs by leveraging existing standards, striking a balance between expressiveness versus ambiguity, and considering the breadth of applicable information with their context of use.

Dynamic measurements of geographical accessibility considering traffic congestion using open data: a cross-sectional assessment for haemodialysis services in Cali, Colombia

Many cities with traffic congestion lack accessibility assessments accounting for traffic congestion and equity considerations but have disaggregated georeferenced municipal-level open data on health services, populations, and travel times big data. We convened a multistakeholder intersectoral collaborative group that developed a digital, web-based platform integrating open and big data to derive dynamic spatial-temporal accessibility measurements (DSTAM) for haemodialysis services. We worked with stakeholders and data scientists and considered people's places of residence, service locations, and travel time to the service with the shortest travel time. Additionally, we predicted the impacts of strategically introducing haemodialysis services where they optimise accessibility. Cross-sectional analyses of DSTAM, accounting for traffic congestion, were conducted using a web-based platform. This platform integrated traffic analysis zones, public census and health services datasets, and Google Distance Matrix API travel-time data. Predictive and prescriptive analytics identified optimal locations for new haemodialysis services and estimated improvements. Primary outcomes included the percentage of residents within a 20-min car drive of a haemodialysis service during peak and free-flow traffic congestion. Secondary outcomes focused on optimal locations to maximise accessibility with new services and potential improvements. Findings were disaggregated by sociodemographic characteristics, providing an equity perspective. The study in Cali, Colombia, used geographic and disaggregated sociodemographic data from the adjusted 2018 Colombian census. Predicted travel times were obtained for two weeks in2020. There were substantial traffic variations. Congestion reduced accessibility, especially among marginalised groups. For 6-12 July, free-flow and peak-traffic accessibility rates were 95.2% and 45.0%, respectively. For 23-29 November, free-flow and peak traffic accessibility rates were 89.1% and 69.7%. The locations where new services would optimise accessibility had slight variation and would notably enhance accessibility and health equity. Establishing haemodialysis services in targeted areas has significant potential benefits. By increasing accessibility, it would enhance urban health and equity. No external or institutional funding was received.

The Impact of Real Estate Investment Trusts (REITs) on the Indian Commercial Real Estate Market: A Study of Investor Perception and Market Performance

The introduction of Real Estate Investment Trusts (REITs) in India has marked a significant evolution in the country's commercial real estate landscape. This paper examines the multifaceted impact of REITs on the Indian commercial real estate market, focusing on key dimensions such as liquidity, transparency, investor access, and market development. Firstly, REITs have enhanced liquidity in the commercial real estate sector by providing investors with a liquid avenue to invest in income-generating properties, thereby reducing the traditionally illiquid nature of real estate investments. This increased liquidity has facilitated capital flow into the market and stimulated transaction activity. Secondly, REITs have contributed to greater transparency in the Indian real estate market. By mandating regular disclosures and adherence to stringent governance standards, REITs have improved information symmetry between investors and property developers, leading to a more efficient allocation of capital and reduced investment risk. Thirdly, the introduction of REITs has widened investor access to commercial real estate assets. Individual investors, institutional funds, and foreign investors now have the opportunity to participate in the market through REIT investments, thereby diversifying their portfolios and potentially earning stable returns from rental income and capital appreciation. Furthermore, REITs have played a pivotal role in the development of the Indian commercial real estate market. Their presence has spurred the professionalization of property management practices, encouraged the adoption of international standards, and catalyzed the growth of ancillary industries such as real estate services and financial advisory firms.

Disparities in access to U.S. quantum information education

Driven in large part by the National Quantum Initiative Act of 2018, quantum information science (QIS) coursework and degree programs are rapidly spreading across U.S. institutions. Yet prior work suggests that access to quantum workforce education is unequally distributed, disproportionately benefiting students at private research-focused institutions whose student bodies are unrepresentative of U.S. higher education as a whole. We use regression analysis to analyze the distribution of QIS coursework across 456 institutions of higher learning as of Fall 2022, identifying statistically significant disparities across institutions in particular along the axes of institution classification, funding, and geographic distribution suggesting today’s QIS education programs are largely failing to reach low-income and rural students. We also conduct a brief analysis of the distribution of emerging dedicated QIS degree programs, discovering much the same trends. We conclude with a discussion of implications for educators, policymakers, and education researchers including specific policy recommendations to direct investments in QIS education to schools serving low-income and rural students, leverage existing grassroots diversity and inclusion initiatives that have arisen within the quantum community, and update and modernize procedures for collecting QIS educational data to better track these trends. Published by the American Physical Society 2024

Abstract 2148: Lung Capillary Endothelium To Arterial Endothelium Transition In Pulmonary Arterial Hypertension

Introduction: Pulmonary arterial hypertension (PAH) is characterized by a progressive increase of pulmonary vascular resistance and obliterative pulmonary vascular remodeling that result in right heart hypertrophy, failure, and premature death. The underlying mechanisms of loss of distal capillary endothelial cells (ECs) and obliterative vascular lesion formation remain unclear. Method and Results: Our recent single-cell RNA sequencing, spatial transcriptomics analysis, RNASCOPE, and immunostaining analysis showed that arterial ECs accumulation and loss of capillary ECs were evident in human PAH patients and pulmonary hypertension (PH) rodents. Pseudotime trajectory analysis of the single-cell RNA sequencing data suggests that lung capillary ECs transit to arterial ECs during the development of PH. Our study also identified CXCL12 as the marker for distal arterial ECs in PH. General capillary EC lineage tracing approach using Plvap-DreERT2; Tdtomato mice demonstrated that general capillary ECs gave rise to arterial ECs during PH development. Genetic deletion of HIF-2a or Notch4 neutralized antibodies normalized the arterial programming in PH. Conclusion: In conclusion, our study demonstrates that general capillary endothelium transits to arterial endothelium through the HIF-2a-Notch4 pathway during the development of PAH. Thus, targeting arterial EC transition might be a novel approach for treating PAH patients. Acknowledgment: This work was supported in part by NIH grants R00HL138278, R01HL158596, R01HL62794, R01HL169509, R01HL170096, AHA Career Development Award 20CDA35310084, The Cardiovascular Research and Education Foundation, Arizona Biomedical Research Centre funding (RFGA2022-01-06), and University of Arizona institution funding to Z.D.

Juxtaglomerular (JG) cell-specific deletion of the NADPH oxidase accessory protein, NOXA1, decreases pro-renin and proteinuria in vivo in a mouse model of diabetes

A large fraction of patients with diabetes develops diabetic nephropathy. Plasma pro-renin levels are elevated in diabetic patients and thought to contribute to hypertension, renal damage and inflammation. Studying the mechanisms by which diabetes reprograms JG cells to increase pro-renin release could provide new targets for kidney disease. We previously found that JG cells from diabetic mice had higher reactive oxygen species production (superoxide and H2O2), pro-renin expression and pro-renin and renin release. We hypothesized that increased ROS production by specific NADPH oxidases (NOXs) in JG cells is responsible for higher pro-renin release and contributes to glomerular damage in diabetes. Western Blots showed that the NADPH oxidase isoform NOX1 and NOXA1 are upregulated in JG cells from diabetic mice (C57=100%; Akita=147±10%; n=4; p<0.05), whereas NOX2 or NOX4 were not different. Confocal microscopy showed that NOX1 and NOXA1 are present in JG cells and co-localize with renin-containing granules (n=3). Silencing NOX1 in primary cultures of JG cells from diabetic mice decreased renin release to C57 control levels; (n=6; p<0.01) whereas silencing NOX4 had no effect (n=6). To study the role of NOXA1 and NOX1 in JG cells in vivo, we used Cas9 mediated silencing in kidneys of control mice. Adenoviruses expressing Cas9 under control of the Ren1 promoter (AV-Ren1-Cas9) and AAV-gRNA-NOXA1 were loaded into 28-day minipumps and delivered into the renal subcapsular space in C57 mice. After 5 weeks, we obtained control (non-transduced) and Ren-Cas9-NOXA1-edited kidneys and isolated JG cells. NOXA1 expression was reduced by 60±22% in isolated JG cells and pro-renin expression was decreased by 46±19% compared to non-transduced kidneys (n=3). We then specifically deleted NOXA1 from JG cells in diabetic mice by subcapsular delivery of AV-Ren1-Cre in the kidney cortex of transgenic NOXA1 floxed diabetic Akita mice. JG cell-specific deletion of NOXA1 in diabetic mice decreased urinary ROS (8-Isoprostane pg/24hrs: Akita=4091±307; NOXA1 JG/KO=3086 ±137; n=4; p<0.05), and glomerular damage as indicated by decrease proteinuria (24h Ualbumin Akita= 98.6± 9.4; NOXA1 JG/KO= 57.8± 16.4 μg/24h; n=4; p<0.05). We conclude that enhanced NOX1/NOXA1 induced ROS in JG cells drive enhanced pro-renin release from JG cells which contribute to glomerular damage in diabetes. Thus, NOXA1/NOX1 in JG cells are a potential new target for diabetic nephropathy. DK105300-RO3 Henry Ford Hospital Institutional Funds. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Unraveling the Mechanism Behind the Ketogenic Diet-Mediated Reversal of Heart Failure in Mice

It has become clear that heart failure involves a host of metabolic alterations, and nutritional or pharmacologic modulation of cardiac metabolism can improve heart failure. We previously studied the role of the mitochondrial pyruvate carrier (MPC) in heart failure, and observed that pyruvate transport into the mitochondria of cardiac myocytes was critical for maintenance of normal cardiac size and function. However, we were also able to prevent or reverse heart failure in cardiac-specific MPC2−/− (cs-MPC2−/−) mice by feeding a low carbohydrate, high fat “ketogenic” diet. Intriguingly, while ketosis was associated with this reversal in heart failure, it was observed that cardiac ketone body oxidation enzymes were downregulated in these hearts, and direct administration of ketone bodies without altering dietary fat did not improve heart failure. The objective of this current study was to define whether ketone body oxidation was necessary for improving heart failure with a ketogenic diet. Wildtype mice were subjected to combined transverse aortic constriction and apical myocardial infarction (TAC-MI) to induce heart failure, were imaged by echocardiography two weeks later and randomized to either low fat control or ketogenic diet for an additional two weeks before repeat echocardiography and euthanasia. Cardiac size and function was also assessed in cs-MPC2−/− mice, mice with cardiac deletion of betahydroxybutyrate dehydrogenase 1 (cs-BDH1−/−, the first enzyme in ketone body oxidation), and cs-MPC2/BDH1−/− double KO mice. Mice were aged to 16 weeks, when MPC−/− hearts have developed dilated cardiomyopathy, and then fed either low fat control or ketogenic diet for 3 weeks before echocardiography and euthanasia. Of the WT mice subjected to TAC-MI, being fed a LF control diet led to further cardiac remodeling and worsened contractile function. However, ketogenic diet feeding completely prevented the progression of cardiac remodeling. cs-BDH1−/− hearts maintained normal size and function, suggesting that lack of ketone oxidation has no overt effect on cardiac function or remodeling. However, as previously reported, cs-MPC2−/− hearts developed dilated cardiomyopathy, which was not significantly altered by combined deletion of BDH1. Switching cs-MPC2−/− or cs-MPC2/BDH1−/− mice to a ketogenic diet was able to significantly reverse the heart failure, suggesting that enhanced ketone oxidation is not the mechanism for improved heart failure. Gene expression from these hearts suggests that ketogenic diet suppresses ketolytic gene expression and enhances expression of fat oxidation genes. Altogether, these findings suggest that improving heart failure with a ketogenic diet is due to stimulation of cardiac fat oxidation and not ketone body metabolism. Project was funded by NIH R00 HL136658 and SLU institutional funds. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Lung capillary endothelium to arterial endothelium transition in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is characterized by a progressive increase of pulmonary vascular resistance and obliterative pulmonary vascular remodeling that result in right heart hypertrophy, failure, and premature death. The underlying mechanisms of loss of distal capillary endothelial cells (ECs) and obliterative vascular lesion formation remain unclear. Our recent single-cell RNA sequencing, spatial transcriptomics analysis, RNASCOPE, and immunostaining analysis showed that arterial ECs accumulation and loss of capillary ECs were evident in human PAH patients and pulmonary hypertension (PH) rodents. Pseudotime trajectory analysis of the single-cell RNA sequencing data suggest that lung capillary ECs transit to arterial ECs during the development of PH. Our study also identified CXCL12 as the marker for arterial ECs in PH. General capillary EC lineage tracing approach using Plvap-DreERT2;Tdtomato mice demonstrated that general capillary ECs gave rise to arterial ECs during PH development. Genetic deletion of HIF-2a or pharmacological inhibition of Notch4 normalized the arterial programming in PH. In conclusion, our study demonstrates that general capillary endothelium transits to arterial endothelium through the HIF-2a-Notch4 pathway during the development of PAH. Thus, targeting arterial EC transition might be a novel approach for treating PAH patients. This work was supported in part by NIH grant R00HL138278, R01HL158596, R01HL62794, R01HL169509, R01HL170096, AHA Career Development Award 20CDA35310084, The Cardiovascular Research and Education Foundation, Arizona Biomedical Research Centre funding (RFGA2022-01-06), and University of Arizona institution funding to Z.D. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A BRIEF STUDY ON STOCK MARKET

The Indian stock market has undergone a remarkable transformation over its century-long history, emerging as a dynamic and sophisticated financial ecosystem that plays a pivotal role in driving the nation's economic growth. With securities traded on prominent exchanges like the Bombay Stock Exchange (BSE) and the National Stock Exchange (NSE), the market serves as a vital platform for capital allocation and investment. Regulated by the Securities and Exchange Board of India (SEBI), it exhibits inclusivity, welcoming a diverse spectrum of participants, from retail investors to institutional funds. Despite facing challenges such as volatility and regulatory compliance, the Indian stock market remains resilient, offering ample opportunities for wealth creation and economic development. Through a comprehensive exploration of its historical evolution, regulatory framework, market participants, and performance metrics, this report aims to provide valuable insights for investors and stakeholders, shedding light on emerging trends and opportunities in the Indian financial landscape.