Developmental State Research Articles

Developmental Changes in Genome Replication Progression in Pluripotent versus Differentiated Human Cells.

DNA replication is a fundamental process ensuring the maintenance of the genome each time cells divide. This is particularly relevant early in development when cells divide profusely, later giving rise to entire organs. Here, we analyze and compare the genome replication progression in human embryonic stem cells, induced pluripotent stem cells, and differentiated cells. Using single-cell microscopic approaches, we map the spatio-temporal genome replication as a function of chromatin marks/compaction level. Furthermore, we mapped the replication timing of subchromosomal tandem repeat regions and interspersed repeat sequence elements. Albeit the majority of these genomic repeats did not change their replication timing from pluripotent to differentiated cells, we found developmental changes in the replication timing of rDNA repeats. Comparing single-cell super-resolution microscopic data with data from genome-wide sequencing approaches showed comparable numbers of replicons and large overlap in origins numbers and genomic location among developmental states with a generally higher origin variability in pluripotent cells. Using ratiometric analysis of incorporated nucleotides normalized per replisome in single cells, we uncovered differences in fork speed throughout the S phase in pluripotent cells but not in somatic cells. Altogether, our data define similarities and differences on the replication program and characteristics in human cells at different developmental states.

A transcriptomic time-series reveals differing trajectories during pre-floral development in the apex and leaf in winter and spring varieties of Brassica napus

Oilseed rape (Brassica napus) is an important global oil crop, with spring and winter varieties grown commercially. To understand the transcriptomic differences between these varieties, we collected transcriptomes from apex and leaf tissue from a spring variety, Westar, and a winter variety, Tapidor, before, during, and after vernalisation treatment, until the plants flowered. Large transcriptomic differences were noted in both varieties during the vernalisation treatment because of temperature and day length changes. Transcriptomic alignment revealed that the apex transcriptome reflects developmental state, whereas the leaf transcriptome is more closely aligned to the age of the plant. Similar numbers of copies of genes were expressed in both varieties during the time series, although key flowering time genes exhibited expression pattern differences. BnaFLC copies on A2 and A10 are the best candidates for the increased vernalisation requirement of Tapidor. Other BnaFLC copies show tissue-dependent reactivation of expression post-cold, with these dynamics suggesting some copies have retained or acquired a perennial nature. BnaSOC1 genes, also related to the vernalisation pathway, have expression profiles which suggest tissue subfunctionalisation. This understanding may help to breed varieties with more consistent or robust vernalisation responses, of special importance due to the milder winters resulting from climate change.

The Political Economy of Exchange Rates and Export-Led Industrialization in South Korea*

ABSTRACT South Korea’s economic trajectory has been one of the most successful stories of post-war catch-up industrialization. The Korean developmental state has used various tools, including the exchange rate, to become an export powerhouse in the twenty-first century. However, the export-led growth strategy has had a distributive conflict with Korea’s working class. Based on post-Keynesian and structuralist economics, this paper assesses the political economy of exchange rate depreciation and export-led industrialization in South Korea. I show that exports as a share of GDP have constantly risen to become the most important growth engine in the Korean economy. This long-term trend, however, has coincided with a decline in the labor income share in South Korea. I formulate the structuralist macroeconomic model to explain dynamics of real wages, real exchange rates, exports, and output. I finally use a vector autoregression (VAR) analysis to show that exchange rate depreciations during modern South Korea (1989Q1–2023Q1) are inflationary and contractionary in the short run. Currency depreciations have ambiguous effects on exports, but they clearly reduce output gaps. On the other hand, an increase in nominal wages is expansionary or varies positively with output gaps.

Logical design of synthetic cis-regulatory DNA for genetic tracing of cell identities and state changes.

Descriptive data are rapidly expanding in biomedical research. Instead, functional validation methods with sufficient complexity remain underdeveloped. Transcriptional reporters allow experimental characterization and manipulation of developmental and disease cell states, but their design lacks flexibility. Here, we report logical design of synthetic cis-regulatory DNA (LSD), a computational framework leveraging phenotypic biomarkers and trans-regulatory networks as input to design reporters marking the activity of selected cellular states and pathways. LSD uses bulk or single-cell biomarkers and a reference genome or custom cis-regulatory DNA datasets with user-defined boundary regions. By benchmarking validated reporters, we integrate LSD with a computational ranking of phenotypic specificity of putative cis-regulatory DNA. Experimentally, LSD-designed reporters targeting a wide range of cell states are functional without minimal promoters. Applied to broadly expressed genes from human and mouse tissues, LSD generates functional housekeeper-like sLCRs compatible with size constraints of AAV vectors for gene therapy applications. A mesenchymal glioblastoma reporter designed by LSD outperforms previously validated ones and canonical cell surface markers. In genome-scale CRISPRa screens, LSD facilitates the discovery of known and novel bona fide cell-state drivers. Thus, LSD captures core principles of cis-regulation and is broadly applicable to studying complex cell states and mechanisms of transcriptional regulation.

The NMR structure of the Ea22 lysogenic developmental protein from lambda bacteriophage

The ea22 gene resides in a relatively uncharacterized region of the lambda bacteriophage genome between the exo and xis genes and is among the earliest genes transcribed upon infection. In lambda and Shiga toxin-producing phages found in enterohemorrhagic E. coli (EHEC) associated with food poisoning, Ea22 favors a lysogenic over lytic developmental state. The Ea22 protein may be considered in terms of three domains: a short amino-terminal domain, a coiled-coiled domain, and a carboxy-terminal domain (CTD). While the full-length protein is tetrameric, the CTD is dimeric when expressed individually. Here, we report the NMR solution structure of the Ea22 CTD that is described by a mixed alpha–beta fold with a dimer interface reinforced by salt bridges. A conserved mobile loop may serve as a ligand for an unknown host protein that works with Ea22 to promote bacterial survival and the formation of new lysogens. From sequence and structural comparisons, the CTD distinguishes lambda Ea22 from homologs encoded by Shiga toxin-producing bacteriophages.

Allometric equations to calculate living and dead fuel loads in Mediterranean species

Determining the structure and fuel load is key to know the flammability of vegetation in the Mediterranean Basin where forest fires are frequent. Determine which plant structural variable is best related to living and dead fuel to develop allometric equations in nine species in the Western Mediterranean Basin. In the east of the Iberian Peninsula (Valencia Province), we measured four structural variables (basal stem diameter, height, maximum diameter and perpendicular diameter) that were related, by means of allometric equations, to the living and dead fuel separated into different size classes. We also analyze fuel changes across developmental states of the studied species, and the vertical distribution of dead fuel. General equations that consider all development states can be used to determine living fuel. However to obtain dead fuel, we recommend using specific equations for each development state and fuel fraction for better accuracy. The basal stem diameter was the best structural variable in almost all cases for estimating fuel in the studied species. Dead fuel load throughout species’ ontological development is a key factor to manage Mediterranean plant communities.

The diverse colours of money: the country-of-origin effects of foreign direct investment within East Asia

In the existing literature on foreign direct investment, it is often assumed that multinational corporations and their direct investments reduce institutional differences among economies. Building upon this assumption, those influenced by management studies and mainstream economics see multinational corporations as an agent that upgrades local business conventions to global standards. Geographers do not usually accept this convergence theory and claim differences among host economies prevents convergence in business practices. The difference between these groups of scholars is that the non-convergence camp acknowledges the resilience of local business practices while the convergence camp does not. The papers comprising this special issue question this shared assumption of foreign direct investment as a cause of convergence. As outlined in this introductory paper, and explored in detail in the following papers, we pay attention to the simple fact that the foreign direct investment is from a company or individual whose business practices are inherently influenced by their experiences of business in the nation or region of origin, and these experiences indelibly influence, to varying degrees, their local operations in investment destination. Once we accept such an obvious fact, recent debates on variety of capitalism and related literatures on the developmental state, welfare regime and other concepts all become relevant to understanding of the local operation of foreign-owned businesses.

Resilience of Psychotherapists through the Lens of The Primary Capacities of Nossrat Peseschkian’s Positive Psychotherapy

This study explores the correlation between the resilience of therapists and the primary capacities of Nossrat Peseschkian’s Positive Psychotherapy theory. The aim of the study is to examine whether the developmental state of these capacities, related to the emotional aspects of an individual, can work towards increasing the resilience of therapists. A cross-sectional study was conducted to collect and analyze numerical data using questionnaires, to examine the relationship between primary capacities as an independent variable and resilience as a dependent variable. The study included 93 participants, psychotherapists from Greece, Romania, UK, Spain, Poland, Ukraine, Germany and Austria, all of them over 24 years of age with more than 1 year of experience as psychotherapists. A statistically significant correlation was found between the therapists’ primary capacities and resilience. Therapists with a higher level of primary capacities were more likely to be resilient in the face of adversity. This suggests that developing primary capacities can help therapists cope with the challenges of their work and maintain their well-being.

Abstract PR13: Single-cell mapping reveals a common origin for diverse subtypes of pancreatic cancer

Abstract The detailed understanding of the molecular basis of tumor initiation and progression is essential for the effective management and treatment of any cancer, including pancreatic cancer. To determine if the stem and progenitor cells can serve as cells of origin for pancreatic cancer, we have created a new mouse strain in which tamoxifen inducible Cre (CreERT2) is knocked into the endogenous locus encoding the stem cell regulator Musashi2 (Msi2). When crossed to a Cre-regulatable Myc transgenic (CAG-LSL-MycT58A) strain, Msi2-CreERT2 mice develop multiple pancreatic cancer subtypes: pancreatic ductal adenocarcinoma (PDAC), adenosquamous carcinoma of the pancreas (ASCP), and acinar cell carcinoma (ACC) following Myc activation in Msi2+ cells in the adult stage. A combination of single-cell genomics with computational analysis of developmental states and lineage trajectories of tumors in our model suggests that oncogenic Myc preferentially triggers the transformation of the most immature subset of Msi2+ cells, leading to the rise of a common pool of pre-cancer cells with multi-lineage potential. These pre-cancer cells subsequently take distinct fates within the same mice by activation of distinct transcriptional programs and large-scale genomic changes. Additionally, combining transcriptomic and functional genomic approaches, we have identified hyaluronan-mediated motility receptor (HMMR) as a potential novel dependency in mouse and human ASCP cells, providing a framework to develop interception strategies for this lethal disease. In summary, our study shows that multiple pancreatic cancer subtypes can arise from a common pool of Msi2+ cells and provides a powerful framework to understand and control the programs that shape divergent fates in pancreatic cancer. Citation Format: Nirakar Rajbhandari, Michael Hamilton, Tannishtha Reya. Single-cell mapping reveals a common origin for diverse subtypes of pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr PR13.

Decoding Ribosome Heterogeneity: A New Horizon in Cancer Therapy.

The traditional perception of ribosomes as uniform molecular machines has been revolutionized by recent discoveries, revealing a complex landscape of ribosomal heterogeneity. Opposing the conventional belief in interchangeable ribosomal entities, emerging studies underscore the existence of specialized ribosomes, each possessing unique compositions and functions. Factors such as cellular and tissue specificity, developmental and physiological states, and external stimuli, including circadian rhythms, significantly influence ribosome compositions. For instance, muscle cells and neurons are characterized by distinct ribosomal protein sets and dynamic behaviors, respectively. Furthermore, alternative forms of ribosomal RNA (rRNAs) and their post-transcriptional modifications add another dimension to this heterogeneity. These variations, orchestrated by spatial, temporal, and conditional factors, enable the manifestation of a broad spectrum of specialized ribosomes, each tailored for potentially distinct functions. Such specialization not only impacts mRNA translation and gene expression but also holds significant implications for broader biological contexts, notably in the realm of cancer research. As the understanding of ribosomal diversity deepens, it also paves the way for exploring novel avenues in cellular function and offers a fresh perspective on the molecular intricacies of translation.

The Conundrum of Imported Models in Africa: A Critical Review of the Ethiopian Developmental State and the Neoliberal-Oriented “Homegrown” Economic Reform

Within the framework of critical development theory, this article first reviews the African experience of imitating external development models, focusing on the impact of neoliberalism on the continent, and the case for the developmental state. It then examines whether Ethiopia once again is abandoning an isomorphic emulation of a self-proclaimed developmental state by taking a stride toward neoliberalism with the ongoing reform since 2018. This reform, as witnessed by fast-tracked currency devaluation, privatization, and the removal of state subsidies, indicates a policy shift geared toward traditional neoliberal prescriptions. It argues that it is better to cautiously reform the Ethiopian developmental state to introduce exact features of the model instead of prematurely abandoning it for unbridled neoliberalism in the name of a “homegrown economic reform” that turned out to be an IMF/WB-brewed adjustment rather than a homegrown rebalancing.

The (surprise) return of development policy space in the multilateral trading system: what the WTO Appellate Body blockage means for the developmental state

Since the establishment of the World Trade Organization (WTO) – which led to a dramatic expansion in the scope of global trade rules and made those rules legally binding on states – scholars have highlighted the constraints it has imposed on development policy space. By prohibiting many of the standard tools of the developmental state, the WTO’s rules have been seen as ‘kicking away the ladder’ for developing countries, preventing them from using the trade and industrial policies needed to catch up with more advanced economies. However, since 2019, the US has disabled the WTO’s enforcement mechanism by blocking judicial appointments to the Appellate Body. As a result, this article shows the trade and development landscape has now changed fundamentally: WTO rules – once a powerful constraint on development policy space – are no longer legally enforceable. The article analyzes two recent landmark disputes – Indonesian nickel export restrictions and Indian export subsidies provided through special economic zones – in which developing countries have successfully blocked WTO panel rulings that would force them to repeal developmentalist policies. Ironically, given that the US was originally the dominant force behind the WTO’s anti-developmentalist rules and its binding dispute settlement system, one important consequence of the US Appellate Body blockage has been the re-emergence of development policy space in the multilateral trading system.

A molecular mechanism for embryonic resetting of winter memory and restoration of winter annual growth habit in wheat.

The staple food crop winter bread wheat (Triticum aestivum) acquires competence to flower in late spring after experiencing prolonged cold in temperate winter seasons, through the physiological process of vernalization. Prolonged cold exposure results in transcriptional repression of the floral repressor VERNALIZATION 2 (TaVRN2) and activates the expression of the potent floral promoter VERNALIZATION 1 (TaVRN1). Cold-induced TaVRN1 activation and TaVRN2 repression are maintained in post-cold vegetative growth and development, leading to an epigenetic 'memory of winter cold', enabling spring flowering. When and how the cold memory is reset in wheat is essentially unknown. Here we report that the cold-induced TaVRN1 activation is inherited by early embryos, but reset in subsequent embryo development, whereas TaVRN2 remains silenced through seed development, but is reactivated rapidly by light during seed germination. We further found that a chromatin reader mediates embryonic resetting of TaVRN1 and that chromatin modifications play an important role in the regulation of TaVRN1 expression and thus the floral transition, in response to developmental state and environmental cues. The findings define a two-step molecular mechanism for re-establishing vernalization requirement in common wheat, ensuring that each generation must experience winter cold to acquire competence to flower in spring.

Where is the development in SA’s developmental state?

The ruling party defines South Africa as a ‘developmental state’, but with its rising job losses, growth that is lower than most of its African neighbours and rising inequality can that really apply? What’s missing, asks John Matisonn.

O Estado de bem-estar desenvolvimentista na Coreia do Sul sob a globalização

ABSTRACT This paper analyzes the expansion of social policies in South Korea during the context of globalization, by linking two theoretical approaches: social investment and the New Developmental State. Applying the case study method, I endorse the hypothesis of complementarily between the welfare state and the developmental state. The article shows that between the 1990s and the 2010s, South Korea expanded all sectors of social policies analyzed. Beyond the expansion of passive policies, active policies (including education) were reshaped in an integrated manner with the industrial policy to promote innovation, pursuing the transition to the knowledge-based society; also the family policy became one of the most generous among OECD countries.

In search of a ‘developmental state’

This Special Issue on Economics and Labour is divided into two sections. It pairs contributions on current economic development with three articles presented at a conference marking 50 years since the Durban Strikes of 1973. That said, all of the authors reflect widely on history and on immediate challenges, both for South Africa and the continent at large.

Desenvolvimento econômico de alta qualidade: a conciliação da China entre crescimento econômico e sustentabilidade ambiental

ABSTRACT This paper aims to examine the concept of “high-quality” economic development, as the new strategy adopted by China to reconcile economic growth and environmental sustainability. It will be argued that it is not possible to understand the prospects for the development of the Chinese economy without considering the institutional framework of State action and the conduct of macroeconomic policy - which allows us to define China as a developmental state. In addition, the main goals and achievements of China in regard to energetic transition will be presented. In this paper, China is taken as a successful example from which Brazil could draw lessons for its own development strategy.

Between Pluralism and Objectivism: Reconsidering Ernst Cassirer's Teleology of Culture

abstract: This paper revisits debates on a tension in Cassirer's philosophy of culture. On the one hand, Cassirer describes a plurality of symbolic forms and claims that each needs to be assessed by its own internal standards of validity. On the other hand, he ranks the symbolic forms in terms of a developmental hierarchy and states that one form, mathematical natural science, constitutes the highest achievement of culture. In my paper, I do not seek to resolve this tension. Rather, I aim to arrive at a better understanding of how it arises, and of the different options that it presents for understanding the development of culture. I discuss three recent attempts at resolving the tension, put forward by Sebastian Luft, Samatha Matherne, and Simon Truwant, respectively. Based on a reconstruction of Cassirer's system of symbolic forms that centralizes the concept of function, I show that the most promising of these attempts, formulated by Truwant, is not successful. I then turn to Cassirer's philosophy of the cultural sciences, the implications of which for the present problem have not yet been sufficiently explored. I argue that in this context, Cassirer develops the contours of an alternative to the function-based view of cultural development. I conclude that this alternative does not resolve the tension either, but that it allows for a reconceptualization of the teleology of culture as open.

Isolation of Mouse Germ Cells by FACS Using Hoechst 33342 and SYTO16 Double Staining.

In the adult mouse testis, germ cells of various developmental cell states co-exist. FACS isolation of cells stained with the DNA dye Hoechst 33342 has been used for many years to sub-divide these cells based on their DNA content. This approach provides an efficient way to obtain broad categories of male germ cells: pre-meiotic spermatogonia, meiotic spermatocytes and post-meiotic spermatids. The addition of a red filter for Hoechst staining enables further sub-division of spermatocytes depending on sub-stages of meiotic prophase. However, separation of different stage spermatids using Hoechst staining alone is not possible. We recently reported a methodology, combining Hoechst staining with a second DNA dye (SYTO16) that enables the further separation of these cells into three sub-populations: round, early elongating, and late elongating spermatids (Gill et al., Cytometry A 101:529-536, 2022). This method makes it possible to obtain rapidly and simply pure fractions of male germ cells from multiple developental stages from the same animal.

The rise and fall of national capitalism

AbstractFor three millennia, there has been a conflict between landed military power (the traditional enforcers, now nation‐states) and urban commerce (capitalists, now a lawless global plutocracy). This ancient battle was resumed by the European Renaissance, culminating in industrial revolution around 1800. This seemed at first to be a victory of the money interest over landed power. In the mid‐nineteenth century, however, the capitalists discovered that they could not manage without crowd control by the traditional enforcers, a compromise between money and landed power (business and government) that unleashed “national capitalism” in political revolutions involving the leading powers of the last century. These generated mass production and consumption at home and a global takeover by European colonial empires, both enabled by a bureaucratic revolution first proposed by Hegel. National capitalism—a merger of industrial capitalism and the “nation” by strong states attempting to modify the former's contradictions through central bureaucracies acting in the interest of the citizen body—became the main form of society after the Second World War, first through developmental states varying from socially responsible capitalism in the United States through social democracy in Europe to communism in the Soviet bloc, with the newly independent former colonies divided between the antagonists in the Cold War. Undermined by financial imperialism in the last four decades, this system is now failing, but humanity is far from achieving a world society to replace it.