Single cell RNA-seq identifies developing corneal cell fates in the human cornea organoid

The cornea is a protective and refractive barrier in the eye crucial for vision. Understanding the human cornea in health, disease and cell-based treatments can be greatly advanced with cornea organoids developed in culture from induced pluripotent stem cells. While a limited number of studies have investigated the single-cell transcriptomic composition of the human cornea, its organoids have not been examined similarly. Here we elucidated the transcriptomic cell fate map of 4 month-old human cornea organoids and the central cornea from three donors. The organoids harbor cell clusters representing corneal epithelium, stroma and endothelium with sub populations that capture signatures of early developmental states. Unlike the adult cornea where the largest cell population is stromal, the organoids develop almost equal proportion of the three major cell types. These corneal organoids offer a three-dimensional platform to model corneal diseases and integrated responses of the different cell types to treatments.

Single-cell RNA sequencing of Plasmodium vivax sporozoites reveals stage- and species-specific transcriptomic signatures

Plasmodium vivax sporozoites reside in the salivary glands of a mosquito before infecting a human host. Previous transcriptome-wide studies in populations of these forms were limited in their ability to elucidate cell-to-cell variation, thereby masking cellular states potentially important in understanding transmission outcomes. In this study, we performed transcription profiling on 9,947 P. vivax sporozoites to assess the extent to which they differ at single-cell resolution. We show that sporozoites residing in the mosquito's salivary glands exist in distinct developmental states, as defined by their transcriptomic signatures. Additionally, relative to P. falciparum, P. vivax displays overlapping and unique gene usage patterns, highlighting conserved and species-specific gene programs. Notably, distinguishing P. vivax from P. falciparum were a subset of P. vivax sporozoites expressing genes associated with translational regulation and repression. Finally, our comparison of single-cell transcriptomic data from P. vivax sporozoite and erythrocytic forms reveals gene usage patterns unique to sporozoites. In defining the transcriptomic signatures of individual P. vivax sporozoites, our work provides new insights into the factors driving their developmental trajectory and lays the groundwork for a more comprehensive P. vivax cell atlas.

Rethinking the Political Economy of Development in Mao's China

This article examines two theoretical frameworks used to evaluate Maoist development. The first is based on neoclassical economic theory, and the second is rooted in the idea that the Chinese Communist Party made China into a state capitalist regime. Both these theoretical frameworks presume to know what economic practices the CCP should have engaged in and fault the Party for not conforming to their standards of judgment. This article finds this normative approach to analyzing Maoist development to be wanting for four reasons. In its drive to depict China as acting anomalously, this normative standpoint insufficiently attends to the empirical specificities of economic activities of the Mao era. It does not take enough into account how China's socialist identity shaped the CCP's economic initiatives. Nor does it dig deep enough into how the geopolitical dynamics of the Cold War influenced Chinese development. This way of writing the history of the Mao period also overlooks similarities between China and other developmental states in Cold War East Asia. This article calls on historians to adopt a different approach to the study of Chinese development and scour available documentation with the aim of comprehending the economic practices of Mao's China on their own terms.

Norway spruce deploys tissue-specific responses during acclimation to cold

Cold acclimation in plants is a complex phenomenon involving numerous stress-responsive transcriptional and metabolic pathways. Existing gene expression studies have primarily addressed cold acclimation responses in herbaceous plants, and few have focused on perennial evergreens, such as conifers, that survive extremely low temperatures during winter. Relative to Arabidopsis leaves, the main transcriptional response of Norway spruce (Picea abies (L.) H. Karst) needles exposed to cold was delayed, and this delay was associated with slower development of freezing tolerance. Despite this difference in timing, our results indicate that, similar to herbaceous species, Norway spruce principally utilizes early response transcription factors (TFs) of the APETALA 2/ethylene-responsive element binding factor (AP2/ERF) superfamily and NAM (no apical meristem)/ATAF (Arabidopsis Transcription Factors)/CUC (cup shaped cotyledon) (NACs). The needles and root of Norway spruce showed contrasting results, in keeping with their different metabolic and developmental states. Regulatory network analysis identified conserved TFs, including a root-specific bHLH101 homolog, and other members of the same TF family with a pervasive role in cold regulation, such as homologs of ICE1 and AKS3, and also homologs of the NAC (anac47 and anac28) and AP2/ERF superfamilies (DREB2 and ERF3), providing new functional insights into cold stress response strategies in Norway spruce.

Remodeling of Cardiac Gap Junctional Cell–Cell Coupling

The heart works as a functional syncytium, which is realized via cell-cell coupling maintained by gap junction channels. These channels connect two adjacent cells, so that action potentials can be transferred. Each cell contributes a hexameric hemichannel (=connexon), formed by protein subuntis named connexins. These hemichannels dock to each other and form the gap junction channel. This channel works as a low ohmic resistor also allowing the passage of small molecules up to 1000 Dalton. Connexins are a protein family comprising of 21 isoforms in humans. In the heart, the main isoforms are Cx43 (the 43 kDa connexin; ubiquitous), Cx40 (mostly in atrium and specific conduction system), and Cx45 (in early developmental states, in the conduction system, and between fibroblasts and cardiomyocytes). These gap junction channels are mainly located at the polar region of the cardiomyocytes and thus contribute to the anisotropic pattern of cardiac electrical conductivity. While in the beginning the cell–cell coupling was considered to be static, similar to an anatomically defined structure, we have learned in the past decades that gap junctions are also subject to cardiac remodeling processes in cardiac disease such as atrial fibrillation, myocardial infarction, or cardiomyopathy. The underlying remodeling processes include the modulation of connexin expression by e.g., angiotensin, endothelin, or catecholamines, as well as the modulation of the localization of the gap junctions e.g., by the direction and strength of local mechanical forces. A reduction in connexin expression can result in a reduced conduction velocity. The alteration of gap junction localization has been shown to result in altered pathways of conduction and altered anisotropy. In particular, it can produce or contribute to non-uniformity of anisotropy, and thereby can pre-form an arrhythmogenic substrate. Interestingly, these remodeling processes seem to be susceptible to certain pharmacological treatment.

Significant β-carboline Alkaloid Harmine in Different Developmental States of Mammals in Vivo: Endogenic or Exogenic?

Background: Several β-carboline alkaloids (βCBs), harmine, harmaline, harmane, and nor-harmane, are effective for Alzheimer’s disease (AD) model mice. They were discovered in some plants, common foodstuffs, and in blank plasma of various mammals. However, whether these compounds in mammals are exogenous or endogenous remained unclear. The exposure levels of these βCBs in plasma and tissues of pup rats, aging rats and volunteer were detected by UPLC-MS/MS.Result: Results showed that harmine was the main compound found in rats, mice, human, and even in newborn rats without consumption. The changes of harmine concentration showed a high dependence with growth (aging), gender and race. And the concentration of harmine in rat plasma showed a decreasing trend during the growth period of 18 months. Conclusion: These results revealed that harmine may be relevant to AD. The exposure level of harmine in plasma indicate that in addition to exogenous ingestion, spontaneous synthesis might be another important source of harmine in mammals.

Global Economic Planning as a Challenge for the Labour Movement

The central line of argument in this contribution is that the urgency of the economic, social and environmental crises demands to go beyond the institutionalist efforts to install more Global Framework Agreements or Decent Work Campaigns that often only come with piecemeal changes, if at all. The social uprisings in various countries around the globe that erupted in 2019 and 2020 underline the emerging pressure towards a broader vision of systemic change. The shift of emphasis towards Global Economic Planning opens up the following perspectives: 1. It allows to study and adapt the methods used by transnational corporations in economic planning for alternative purposes. 2. It allows to retrieve experiences made both in capitalist planning, i.e. in the framework of industrial policy and developmental states, and in socialist planning and to apply enhanced versions of both. 3. It allows to intervene strategically in order to exploit the potentials of renewable energy for which investment is stagnating globally. 4. It offers an avenue for the labour movement to become a reliable partner of environmental initiatives and the global climate movement. 5. It can provide an avenue for mass participation in systemic change with concrete objectives like the conversion of the automobile industry, decentralised renewable energy grids, and public and community based health and care systems.