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Adenoviruses are commonly utilized as viral vectors for gene therapy, genetic vaccines, and recombinant protein expression. To generate replication-defective adenoviruses, E1-complementing cell lines such as HEK293A are utilized; however, limitations remain. Repeated passage of E1-deleted virus in HEK293A cells increases the occurrence of replication-competent adenoviruses (RCAs). In the present study, we developed a novel cell line originating from human primary cells. L132 cells were transduced two times with E1-encoded retrovirus and three times with E1A-encoded retrovirus. Finally, we selected the most productive L132 cell line for generation of RCA-free adenovirus, GT541. GT541 can serve as an alternative cell line to HEK293A and other adenovirus-producing cells. [ABSTRACT FROM AUTHOR]

Abstract Adenoviruses are commonly utilized as viral vectors for gene therapy, genetic vaccines, and recombinant protein expression. To generate replication-defective adenoviruses, E1-complementing cell lines such as HEK293A are utilized; however, limitations remain. Repeated passage of E1-deleted virus in HEK293A cells increases the occurrence of replication-competent adenoviruses (RCAs). In the present study, we developed a novel cell line originating from human primary cells. L132 cells were transduced two times with E1-encoded retrovirus and three times with E1A-encoded retrovirus. Finally, we selected the most productive L132 cell line for generation of RCA-free adenovirus, GT541. GT541 can serve as an alternative cell line to HEK293A and other adenovirus-producing cells.

Summary: Soybean is a typical short‐day crop, and most commercial soybean cultivars are restricted to a relatively narrow range of latitudes due to photoperiod sensitivity. Photoperiod sensitivity hinders the utilization of soybean germplasms across geographical regions. When grown in temperate regions, tropical soybean responds to prolonged day length by increasing the vegetative growth phase and delaying flowering and maturity, which often pushes the harvest window past the first frost date. In this study, we used CRISPR/LbCas12a to edit a North American subtropical soybean cultivar named 06KG218440 that belongs to maturity group 5.5. By designing one gRNA to edit the nuclear localization signal (NLS) regions of both E1 and E1Lb, we created a series of new germplasms with shortened flowering time and time to maturity and determined their favourable latitudinal zone for cultivation. The novel partial function alleles successfully achieve yield and early maturity trade‐offs and exhibit good agronomic traits and high yields in temperate regions. This work offers a straightforward editing strategy to modify subtropical and tropical soybean cultivars for temperate growing regions, a strategy that could be used to enrich genetic diversity in temperate breeding programmes and facilitate the introduction of important crop traits such as disease tolerance or high yield. [ABSTRACT FROM AUTHOR]

This article proposes a two-country AK model of growth with cross-country knowledge diffusion and endogenous migration to study the relationship between migration, income inequality, and economic growth. In contrast with mainstream AK literature, the article shows that introducing knowledge diffusion from rich to poor countries makes AK models predict conditional convergence, but also that migration tends to cool the catching-up process of poorer economies. When testing the robustness of the policy implications of the AK literature in the presence of migration, we find that subsidizing capital accumulation in frontier countries stimulates migration and worldwide growth, but also that it increases cross-country inequalities in terms of both income and technology. On the contrary, subsidizing capital accumulation in non-frontier countries reduces migration and mitigates inequalities worldwide, but has no effects on the long-run pace of economic growth of the two countries. [ABSTRACT FROM AUTHOR]

This paper discusses the risks that businesses face in the tax system from the point of view of the cycle of money. The current research is about the influence of companies that participate in global tax transactions on the tax revenue. The results show that controlled transactions have a negative impact on the GDP and tax revenue, discouraging any uncontrolled investments. The diminished risk increases the tax revenue. The objective of this research is to show that a tax policy of a low tax rate increases uncontrolled transactions, leading to a growth of GDP and tax revenue. This work complies with the theory of the Cycle of Money. The impact of risk on tax revenue has been determined by comparing results with and without this factor. The Q.E. method uses mathematics and programming, allowing the determination of an appropriate equation by a feedback procedure. An econometric analysis is applied to check the results of the model. A special technique is introduced, for the first time, to identify the risk by the sensitivity impact of one factor to another one. Sensitivity is determined as the ability of one factor to counteract instantly the changes of another one. If the counteract is instant, it is considered that the sensitivity is high. If the counteract delays, it is determined that the sensitivity is low. For high sensitivity, the risk is low, and the adjustment is the appropriate one. For low sensitivity, the risk is high, as the adjustment is not adequate.

Simple Summary: The translational gap poses a challenge for therapeutic cancer vaccine development, including HPV-specific therapeutic vaccines. The aim of this study was to evaluate a new human ex vivo PBMC assay that mimics how viral-vectored vaccines induce T-cell responses in vivo. In brief, PBMCs are taken through rounds of stimulation by co-culturing with syngeneic DCs, which have been previously matured and transduced with the viral-vector-based vaccine. We evaluated the assay using a novel HPV16-specific therapeutic vaccine in healthy human donors with pre-existing T-cell responses against HPV16 to simulate a therapeutic setting. The pre-existing T-cell responses were effectively boosted to a larger extent by vaccine-transduced DCs than by peptide-pulsing, and the T cells could specifically recognize and kill HPV16+ human cancer cells. Additionally, this study supports the use of nucleic-acid-based vaccines for optimal cancer recognition and indicates an immunological advantage of targeting the HPV E1 gene. Persistent human papillomavirus (HPV) infection is responsible for practically all cervical and a high proportion of anogenital and oropharyngeal cancers. Therapeutic HPV vaccines in clinical development show great promise in improving outcomes for patients who mount an anti-HPV T-cell response; however, far from all patients elicit a sufficient immunological response. This demonstrates a translational gap between animal models and human patients. Here, we investigated the potential of a new assay consisting of co-culturing vaccine-transduced dendritic cells (DCs) with syngeneic, healthy, human peripheral blood mononuclear cells (PBMCs) to mimic a human in vivo immunization. This new promising human ex vivo PBMC assay was evaluated using an innovative therapeutic adenovirus (Adv)-based HPV vaccine encoding the E1, E2, E6, and E7 HPV16 genes. This new method allowed us to show that vaccine-transduced DCs yielded functional effector T cells and unveiled information on immunohierarchy, showing E1-specific T-cell immunodominance over time. We suggest that this assay can be a valuable translational tool to complement the known animal models, not only for HPV therapeutic vaccines, and supports the use of E1 as an immunotherapeutic target. Nevertheless, the findings reported here need to be validated in a larger number of donors and preferably in patient samples. [ABSTRACT FROM AUTHOR]

El objetivo de este trabajo es cuantificar la relación negativa entre actividad económica y la contención de la COVID-19 mediante la implementación de intervenciones no farmacéuticas en Paraguay. Para esto, calibramos el modelo desarrollado por Eichenbaum, Rebelo y Trabandt con datos de Paraguay. Utilizamos el modelo para simular la trayectoria de la actividad económica, dados distintos escenarios de infección. Consideramos tres casos de estudio. En el primero, consideramos una flexibilización de las medidas de intervención no farmacéuticas aún vigentes. En el segundo, estudiamos el impacto económico de contener una aceleración de la infección. En el tercer caso, analizamos una reducción de la infección y su efecto en la economía. Mediante el estudio de estos casos obtenemos una aproximación del costo económico de contener la infección.

The characterization of how entrepreneurial a region or country is, has generally been shaped by a narrow view of what actually constitutes entrepreneurship. In the case of Germany, this has led to a characterization of Germany as not being particularly entrepreneurial. Such a view is at odds with the remarkable, high-performing family business, widely held to be the backbone of the economy. The purpose of this paper is to suggest that the interpretation prevalent in entrepreneurship literature is problematic due to a too narrow operationalization of the entrepreneurship concept. As Zahra (2007; 2014) emphasized, context matters for entrepreneurship, especially on a local or spatial level. One particular organizational manifestation of entrepreneurship, family business, may be congruent in specific spatial and institutional contexts but not in others. Other geographic and institutional contexts may be congruent with the contrasting startups. Thus, an important and novel contribution of this paper is to analyze the geography of family business as distinct from startups: two ends of the entrepreneurship continuum, embedded in different kinds of entrepreneurial ecosystems. We generate innovative maps working with official data, showing the distinct distribution of both kinds of entrepreneurship in different ecosystems. These findings are connected with spatial effects, living conditions and lead to recommendations for policy measures. The paper focuses on Germany, because startups as well as family business are prevalent and can be found in all regions. [ABSTRACT FROM AUTHOR]

The extracellular ubiquitin–proteasome system is involved in sperm binding to and/or penetration of the vitelline coat (VC), a proteinaceous egg coat, during fertilization of the ascidian (Urochordata) Halocynthia roretzi. It is also known that the sperm receptor on the VC, HrVC70, is ubiquitinated and degraded by the sperm proteasome during the sperm penetration of the VC and that a 700-kDa ubiquitin-conjugating enzyme complex is released upon sperm activation on the VC, which is designated the "sperm reaction". However, the de novo function of ubiquitin-activating enzyme (UBA/E1) during fertilization is poorly understood. Here, we show that PYR-41, a UBA inhibitor, strongly inhibited the fertilization of H. roretzi. cDNA cloning of UBA1 and UBA6 from H. roretzi gonads was carried out, and their 3D protein structures were predicted to be very similar to those of human UBA1 and UBA6, respectively, based on AlphaFold2. These two genes were transcribed in the ovary and testis and other organs, among which the expression of both was highest in the ovary. Immunocytochemistry showed that these enzymes are localized on the sperm head around a mitochondrial region and the follicle cells surrounding the VC. These results led us to propose that HrUBA1, HrUBA6, or both in the sperm head mitochondrial region and follicle cells may be involved in the ubiquitination of HrVC70, which is responsible for the fertilization of H. roretzi. [ABSTRACT FROM AUTHOR]

Summary: Soybean (Glycine max) is a major source of protein and edible oil world‐wide and is cultivated in a wide range of latitudes. However, it is extremely sensitive to photoperiod, which influences flowering time, maturity, and yield, and severely limits soybean latitude adaptation.In this study, a genome‐wide association study (GWAS) identified a novel locus in accessions harboring the E1 allele, called Time of flowering 8 (Tof8), which promotes flowering and enhances adaptation to high latitude in cultivated soybean. Gene functional analyses showed that Tof8 is an ortholog of Arabidopsis FKF1.We identified two FKF1 homologs in the soybean genome. Both FKF1 homologs are genetically dependent on E1 by binding to E1 promoter to activate E1 transcription, thus repressing FLOWERING LOCUS T 2a (FT2a) and FT5a transcription, which modulate flowering and maturity through the E1 pathway.We also demonstrate that the natural allele FKF1bH3 facilitated adaptation of soybean to high‐latitude environments and was selected during domestication and improvement, leading to its rapid expansion in cultivated soybean. These findings provide novel insights into the roles of FKF1 in controlling flowering time and maturity in soybean and offer new means to fine‐tune adaptation to high latitudes and increase grain yield. [ABSTRACT FROM AUTHOR]

Summary: Flowering time is one of important agronomic traits determining the crop yield and affected by high temperature. When facing high ambient temperature, plants often initiate early flowering as an adaptive strategy to escape the stress and ensure successful reproduction. However, here we find opposing ways in the short‐day crop soybean to respond to different levels of high temperatures, in which flowering accelerates when temperature changes from 25 to 30 °C, but delays when temperature reaches 35 °C under short day. phyA‐E1, possibly photoperiodic pathway, is crucial for 35 °C‐mediated late flowering, however, does not contribute to promoting flowering at 30 °C. 30 °C‐induced up‐regulation of FT2a and FT5a leads to early flowering, independent of E1. Therefore, distinct responsive mechanisms are adopted by soybean when facing different levels of high temperatures for successful flowering and reproduction. [ABSTRACT FROM AUTHOR]

Vaccine-associated rubella is a very rare adverse effect after rubella vaccination; we report the characteristics of a young women who, after a vaccination campaign where she received three different vaccines against influenza, tetanus/diphtheria, and measles/rubella, developed a fever and rash consistent with rubella disease that was confirmed by sequencing of the virus. The evolution was favorable. The woman had two close contacts who did not develop the disease. Follow-up of the patient and her contacts was important to detect complications and for epidemiology surveillance. [ABSTRACT FROM AUTHOR]

We develop a generally applicable full‐information inference method for heterogeneous agent models, combining aggregate time series data and repeated cross‐sections of micro data. To handle unobserved aggregate state variables that affect cross‐sectional distributions, we compute a numerically unbiased estimate of the model‐implied likelihood function. Employing the likelihood estimate in a Markov Chain Monte Carlo algorithm, we obtain fully efficient and valid Bayesian inference. Evaluation of the micro part of the likelihood lends itself naturally to parallel computing. Numerical illustrations in models with heterogeneous households or firms demonstrate that the proposed full‐information method substantially sharpens inference relative to using only macro data, and for some parameters micro data is essential for identification. [ABSTRACT FROM AUTHOR]

The distribution of elite soybean (Glycine max) cultivars is limited due to their highly sensitive to photoperiod, which affects the flowering time and plant architecture. The recent emergence of CRISPR/Cas9 technology has uncovered new opportunities for genetic manipulation of soybean. The major maturity gene El of soybean plays a critical role in soybean photoperiod response. Here, we performed CRISPR/Cas9-mediated targeted mutation of E1 gene in soybean cultivar Tianlong1 carrying the dominant E1 to investigate its precise function in photoperiod regulation, especially in plant architecture regulation. Four types of mutations in the E1 coding region were generated. No off-target effects were observed, and homozygous trans-clean mutants without T-DNA were obtained. The photoperiod sensitivity of e1 mutants decreased relative to the wild type plants; however, e1 mutants still responded to photoperiod. Further analysis revealed that the homologs of E1, E1-La, and E1-Lb, were up-regulated in the e1 mutants, indicating a genetic compensation response of E1 and its homologs. The e1 mutants exhibited significant changes in the architecture, including initiation of terminal flowering, formation of determinate stems, and decreased branch numbers. To identify E1-regulated genes related to plant architecture, transcriptome deep sequencing (RNA-seq) was used to compare the gene expression profiles in the stem tip of the wild-type soybean cultivar and the e1 mutants. The expression of shoot identity gene Dt1 was significantly decreased, while Dt2 was significantly upregulated. Also, a set of MADS-box genes was up-regulated in the stem tip of el mutants which might contribute to the determinate stem growth habit. [ABSTRACT FROM AUTHOR]

Foreign direct investment (FDI) is an important driver of countries’ economic development. Factors such as looser environmental regulations may cause dirty FDI to flow mainly to developing countries. This is explained by the Pollution Haven Hypothesis. The paper aims to investigate whether the Pollution Haven Hypothesis is valid in Turkey using the nonlinear autoregressive distributed lag (NARDL) approach for the period 1974–2017. The results show that FDI inflows and carbon emissions have asymmetric effects in both the short and long term for Turkey, supporting the Pollution Haven Hypothesis. Furthermore, there is a link between carbon emissions and trade openness, manufacturing and economic growth. Policymakers should develop the policies necessary to transfer clean technologies to Turkey by providing improvements and technical advances for a more efficient energy use.

Soybean (Glycine max (L.) Merr.), a typical short-day plant, is sensitive to photoperiod, which limits the geographical range for its cultivation. In the flowering pathway regulated by photoperiod, E1, a flowering inhibitor in soybean, plays the dominant role in flowering time regulation. Two E1 homologs, E1-like-a (E1La) and E1-like-b (E1Lb), play overlapping or redundant roles in conjunction with E1. In the present study, E1 and E1La/b were simultaneously silenced via RNA interference (RNAi) in Zigongdongdou (ZGDD), an extremely late-flowering soybean landrace from southern China. As a result, RNAi lines showed a much earlier-flowering phenotype and obvious photoperiod insensitivity compared with wild-type (WT) plants. In RNAi transgenic plants, the expression levels of flowering inhibitor GmFT4 and flowering promoters GmFT2a/GmFT5a were significantly down- and up-regulated, respectively. Further, the maturity group (MG) of the RNAi lines was reduced from WT ZGDD's MG VIII (extremely late-maturity) to MG 000 (super-early maturity), which can even grow in the northernmost village of China located at a latitude of 53.5°N. Our study confirms that E1 and E1La/b can negatively regulate flowering time in soybean. The RNAi lines generated in this study, with early flowering and maturity traits, can serve as valuable materials and a technical foundation for breeding soybeans that are adapted to high-latitude short-season regions.

Distributional extensions of the benchmark AK endogenous growth model and of the Ramsey model are presented in this paper. The resulting geographic growth model - a forward-backward parabolic partial differential equation (PDE) over a bounded spatial domain - is governed by two main driving forces: a spatial friction in the reallocation of physical capital, and a spatial arbitrage driving the reallocation of savings. The spatial AK model solution, starting from an unequal distribution of capital, displays convergence over time to a spatially homogeneous balanced growth path with positive growth rates. The spatial Ramsey model potentially contains both diffusive and agglomerative spatial forces. If there are no agglomerative forces, the solution displays convergence to a spatially homogenous steady state, but if an agglomerative force exists, there is increasing spatial concentration of capital over time. This shows that convergence in the aggregate can be consistent with different distribution profiles over locations. An additional contribution of the paper is to develop a distributive comparative dynamics analysis for a spatially heterogeneous productivity shock. It is shown that, although there is redistribution of consumption across locations, technological inequality is persistent. [ABSTRACT FROM AUTHOR]

Abstract Background The leaf is a determinate organ essential for photosynthesis, whose size and shape determine plant architecture and strongly affect agronomic traits. In soybean, the molecular mechanism of leaf development is not well understood. The flowering repressor gene E1, which encodes a legume-specific B3-like protein, is known to be the gene with the largest influence on soybean flowering and maturity. However, knowledge of its potential other functions remains poor. Results Here, we identified a novel function of E1 protein in leaf development. Unifoliolate leaves of E1-overexpression (E1-OE) lines were smaller and curlier than those of wild type DongNong 50 (DN50) and Williams 82 (W82). Transverse histological sections showed disorganized cells and significantly elevated palisade tissue number, spongy tissue number, and bulliform cell number in E1-OE lines. Our results indicate that E1 binds to the promoters of the leaf- development-related CINCINNATA (CIN)-like TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) transcription factor genes to negatively regulate their expression. Conclusions Our findings identify E1 as an important new factor in soybean leaf development.

The extracellular ubiquitin–proteasome system is involved in sperm binding to and/or penetration of the vitelline coat (VC), a proteinaceous egg coat, during fertilization of the ascidian (Urochordata) Halocynthia roretzi. It is also known that the sperm receptor on the VC, HrVC70, is ubiquitinated and degraded by the sperm proteasome during the sperm penetration of the VC and that a 700-kDa ubiquitin-conjugating enzyme complex is released upon sperm activation on the VC, which is designated the “sperm reaction”. However, the de novo function of ubiquitin-activating enzyme (UBA/E1) during fertilization is poorly understood. Here, we show that PYR-41, a UBA inhibitor, strongly inhibited the fertilization of H. roretzi. cDNA cloning of UBA1 and UBA6 from H. roretzi gonads was carried out, and their 3D protein structures were predicted to be very similar to those of human UBA1 and UBA6, respectively, based on AlphaFold2. These two genes were transcribed in the ovary and testis and other organs, among which the expression of both was highest in the ovary. Immunocytochemistry showed that these enzymes are localized on the sperm head around a mitochondrial region and the follicle cells surrounding the VC. These results led us to propose that HrUBA1, HrUBA6, or both in the sperm head mitochondrial region and follicle cells may be involved in the ubiquitination of HrVC70, which is responsible for the fertilization of H. roretzi.

Phytochromes have a crucial role in the regulation of flowering in many plants, but the underlying molecular mechanisms vary among species. Recently, Lin et al. described a unique phytochrome A (phyA)-controlled photoperiodic flowering pathway in soybean (Glycine max), revealing a novel mechanism for photoperiodic regulation of flowering. [ABSTRACT FROM AUTHOR]

We integrate an epidemiological model, augmented with contact and mobility analyses, with a two‐sector macroeconomic model, to assess the economic costs of labor supply disruptions in a pandemic. The model is designed to capture key characteristics of the U.S. input–output tables with a core sector that produces intermediate inputs not easily replaceable by the other sectors, possibly subject to minimum‐scale requirements. Using epidemiological and mobility data to inform our exercises, we show that the reduction in labor services due to the observed social distancing (spontaneous and mandatory) could explain up to 6–8 percentage points of the roughly 12% U.S. GDP contraction in the second quarter of 2020. We show that public measures designed to protect workers in core industries and occupations with tasks that cannot be performed from home, can flatten the epidemiological curve at reduced economic costs—and contain vulnerabilities to supply disruptions, namely a new surge of infections. Using state‐level data for the United States, we provide econometric evidence that spontaneous social distancing was no less costly than mandated social distancing. [ABSTRACT FROM AUTHOR]

Financialization has been growing importance in macroeconomic perspectives since the finance-dominated capitalist relations have captured many of the specific positions in an aggregate economy. However, the empirical literature has substantially ignored the examination of the link between an increasing scale of financialization and the rising income inequality. In this study, a major hypothesis is based on the fact that the finance-dominated capitalism has a considerable effect on distributional practices through the channels of bargaining power. By applying the Kaleckian approach, the paper investigates the relationship between financialization and the labor share of national income using a panel dataset of 52 countries over the 1992-2012 period. The results suggest that a higher level of stock market development leads to a more unequal distribution of income and, thus, to the decline of wage share in the national income. Other factors such as globalization and technical change can also exacerbate the decline of wages, coupled with a decrease in the bargaining position of labor measured by unemployment rate and labor force participation rate.

Background: The leaf is a determinate organ essential for photosynthesis, whose size and shape determine plant architecture and strongly affect agronomic traits. In soybean, the molecular mechanism of leaf development is not well understood. The flowering repressor gene E1, which encodes a legume-specific B3-like protein, is known to be the gene with the largest influence on soybean flowering and maturity. However, knowledge of its potential other functions remains poor. Results: Here, we identified a novel function of E1 protein in leaf development. Unifoliolate leaves of E1-overexpression (E1-OE) lines were smaller and curlier than those of wild type DongNong 50 (DN50) and Williams 82 (W82). Transverse histological sections showed disorganized cells and significantly elevated palisade tissue number, spongy tissue number, and bulliform cell number in E1-OE lines. Our results indicate that E1 binds to the promoters of the leaf- development-related CINCINNATA (CIN)-like TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) transcription factor genes to negatively regulate their expression. Conclusions: Our findings identify E1 as an important new factor in soybean leaf development. [ABSTRACT FROM AUTHOR]