Coronavirus disease 2019 (COVID-19) is the latest respiratory pandemic caused by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). Although infection initiates in the proximal ...airways, severe and sometimes fatal symptoms of the disease are caused by infection of the alveolar type 2 (AT2) cells of the distal lung and associated inflammation. In this study, we develop primary human lung epithelial infection models to understand initial responses of proximal and distal lung epithelium to SARS-CoV-2 infection. Differentiated air-liquid interface (ALI) cultures of proximal airway epithelium and alveosphere cultures of distal lung AT2 cells are readily infected by SARS-CoV-2, leading to an epithelial cell-autonomous proinflammatory response with increased expression of interferon signaling genes. Studies to validate the efficacy of selected candidate COVID-19 drugs confirm that remdesivir strongly suppresses viral infection/replication. We provide a relevant platform for study of COVID-19 pathobiology and for rapid drug screening against SARS-CoV-2 and emergent respiratory pathogens.
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•Human alveospheres are composed of renewing AT2 cells and AT1-like cells•Alveolar epithelial cells are efficiently infected by SARS-CoV-2 in vitro•Interferon signaling is activated in SARS-CoV-2-infected alveolar epithelial cells•Lung organoid models provide a platform for drug discovery and disease modeling
In vitro models of human lung epithelium, including diverse cell types of the proximo-distal axis, are critical for modeling infection. Mulay et al. show that alveospheres, with epithelial type 2- and type 1-like cells, are infected by SARS-CoV-2, initiating an interferon response, and serve as a platform for screening antiviral drugs.
Coronavirus disease 2019 (COVID-19) is a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is defined by respiratory symptoms, but cardiac complications ...including viral myocarditis are also prevalent. Although ischemic and inflammatory responses caused by COVID-19 can detrimentally affect cardiac function, the direct impact of SARS-CoV-2 infection on human cardiomyocytes is not well understood. Here, we utilize human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as a model to examine the mechanisms of cardiomyocyte-specific infection by SARS-CoV-2. Microscopy and RNA sequencing demonstrate that SARS-CoV-2 can enter hiPSC-CMs via ACE2. Viral replication and cytopathic effect induce hiPSC-CM apoptosis and cessation of beating after 72 h of infection. SARS-CoV-2 infection activates innate immune response and antiviral clearance gene pathways, while inhibiting metabolic pathways and suppressing ACE2 expression. These studies show that SARS-CoV-2 can infect hiPSC-CMs in vitro, establishing a model for elucidating infection mechanisms and potentially a cardiac-specific antiviral drug screening platform.
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Human iPSC-derived cardiomyocytes are susceptible to SARS-CoV-2 infectionACE2 antibody blunts SARS-CoV-2 infection in cardiomyocytesInfected human iPSC-derived cardiomyocytes activate viral clearance pathways
Sharma et al. demonstrate that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are susceptible to SARS-CoV-2 infection. This establishes a platform for understanding the mechanisms of cardiac-specific infection by SARS-CoV-2 in vitro and could potentially be employed to develop antiviral compounds.
Viruses hijack host cell metabolism to acquire the building blocks required for replication. Understanding how SARS-CoV-2 alters host cell metabolism may lead to potential treatments for COVID-19. ...Here we profile metabolic changes conferred by SARS-CoV-2 infection in kidney epithelial cells and lung air-liquid interface (ALI) cultures, and show that SARS-CoV-2 infection increases glucose carbon entry into the TCA cycle via increased pyruvate carboxylase expression. SARS-CoV-2 also reduces oxidative glutamine metabolism while maintaining reductive carboxylation. Consistent with these changes, SARS-CoV-2 infection increases the activity of mTORC1 in cell lines and lung ALI cultures. Lastly, we show evidence of mTORC1 activation in COVID-19 patient lung tissue, and that mTORC1 inhibitors reduce viral replication in kidney epithelial cells and lung ALI cultures. Our results suggest that targeting mTORC1 may be a feasible treatment strategy for COVID-19 patients, although further studies are required to determine the mechanism of inhibition and potential efficacy in patients.
•Neoliberal institutional reforms involve power, not just technical expertise.•Our power in institutions matrix highlights multiple dimensions of power in reforms.•Neoliberalism creates winners and ...losers but also produces new distributive politics.•Citizen groups wield counter-powers to shape elite-dominated institutional reforms.•Access to power is central to institutions for inclusive and sustainable development.
Despite the recognition that institutions matter for international development, the debates over institutional reforms tend to obscure the role of power. Neoliberal models of development are often promoted in terms of their technical merits and efficiency gains and rarely account for the multiple ways that social, economic and political power shape institutional design and institutional change. Even recent efforts to address power tend to conceptualize it too narrowly. This special issue seeks to rethink the role of power in institutional creation and change in the context of persistent neoliberalism. In the introduction, we synthesize the literature on the nature of power to develop a new conceptual framework – a power in institutions matrix – that highlights the multiple dimensions of power involved in institutional development and change. We argue that such a theoretically-informed mapping of power in institutions will enable scholars, practitioners, and citizen groups to go beyond the standard critiques in order to analyze the multifaceted effects of neoliberal institutional change. Our introduction draws on an extensive literature review as well as the special issue contributors who examine institutional change in a variety of policy sectors in Africa, South Asia, Latin America, and North America. We find that a range of diverse local, national and transnational actors, with disparate access to power, negotiate institutional changes from above and below through overt imposition of and resistance to new rules, influence of agendas, and promotion of discourses. Neoliberalism thus creates a new distributive politics. The special issue thus offers a theoretically-grounded approach for linking international and domestic power differences to the process of institutional change, with a specific focus on equity and sustainability. In a departure from the current literature’s focus on elite bargains, we showcase the efforts by less powerful groups to gain a foothold in decision-making processes.
Royuela V. and García G. A. Economic and social convergence in Colombia, Regional Studies. Gross domestic product (GDP) has usually been used as a proxy for human well-being. Nevertheless, other ...social aspects should also be considered, such as life expectancy, infant mortality, educational enrolment and crime issues. This paper investigates economic and social convergence between regions in Colombia in the period 1975-2005. The main results confirm that there is convergence in Colombia in key social variables, although not in the classic economic variable, GDP per capita. It is also found that spatial autocorrelation reinforces convergence processes through deepening market and social factors, while isolation condemns regions to non-convergence
•Documents recurrent patterns of elite capture in community forestry associations.•Finds foresters and timber corporations are central actors in these processes.•Links these patterns to power fields, ...shaped by enduring techno-bureaucratic logics.•Neoliberalization tends to further entrench elites’ power.•Shows these patterns are not unchangeable; they are also recurrently contested.
Problems of elite capture continue to present challenges for sustainable and equitable forest governance around the world. Our understanding of elite capture, however, remains limited by conceptual approaches that pay insufficient attention to power in its various dimensions. Drawing on critical institutionalism and political ecology, I analyze how the power veiled in political-economic structures or ‘power fields’, embedded with local institutions and relations of conflict and negotiation, helps (re)produce elite power and persistence. I pay particular attention to the role of foresters as crucial yet understudied elite actors in community forestry. I employ an over-time comparative case study of processes of elite capture in four regional inter-community forestry associations (FAs) in the state of Durango, Mexico. I argue that foresters’ persistent capture of FAs is related to multi-layered power inequalities and persistent democratic deficits reproduced by techno-bureaucratic forestry and authoritarian corporatist logics. At the same time, I posit that this capture is not definite but is continually transformed by social struggles and grassroots institutional innovations.
Studying the stability of hydrogen-bonded nucleobase pairs, at the heart of the genetic code, is of utmost importance for an in-depth understanding of basic mechanisms of life and biomolecular ...evolution. We present here a VUV single photon ionization dynamic study of the nucleobase pair adenine-thymine (AT), revealing its ionization and dissociative ionization thresholds via double imaging electron/ion coincidence spectroscopy. The experimental data, consisting of cluster mass-resolved threshold photoelectron spectra and photon energy-dependent ion kinetic energy release distributions, allow the unambiguous distinction of the dissociation of AT into protonated adenine AH+ and a dehydrogenated thymine radical T(−H) from dissociative ionization processes of other nucleobase clusters. Comparison to high-level ab initio calculations indicates that our experimental observations can be explained by a single hydrogen-bonded conformer present in our molecular beam and allows the estimation of an upper limit of the barrier of the proton transfer in the ionized AT pair.
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