Managing government debt.

To construct a stochastic version of [R. J. Barro, , 940-971 (1979)] normative model of tax rates and debt/GDP dynamics, we add risks and markets for trading them along lines suggested by [K.

Three world wars: Fiscal-monetary consequences.

Directed by a consolidated government budget constraint, we compare US monetary–fiscal responses to World Wars I and II and the War on COVID-19.

Aberrant inflammatory responses to type I interferon in STAT2 or IRF9 deficiency.

Background: Inflammatory phenomena such as hyperinflammation or hemophagocytic lymphohistiocytosis are a frequent yet paradoxical accompaniment to virus susceptibility in patients with impairment of type I interferon (IFN-I) signaling caused by deficiency of signal transducer and activator of transcription 2 (STAT2) or IFN regulatory factor 9 (IRF9).

Objective: We hypothesized that altered and/or prolonged IFN-I signaling contributes to inflammatory complications in these patients.

Methods: We explored the signaling kinetics and residual transcriptional responses of IFN-stimulated primary cells from individuals with complete loss of one of STAT1, STAT2, or IRF9 as well as gene-edited induced pluripotent stem cell-derived macrophages.

Earnings growth and the wealth distribution.

As measured by Gini coefficients, fractile inequalities, and tail power laws, wealth is distributed less equally across people than are labor earnings. We study how luck, attitudes that shape saving decisions, and growth rates of labor earnings balance each other in ways that simultaneously shape joint distributions across people of labor earnings, age, and wealth together with an equilibrium rate of return on savings that plays a pivotal role in balancing contending forces. Strong motives for people to save and for firms to demand capital raise an equilibrium interest rate enough to make wealth grow faster than labor earnings.

Brief history of US debt limits before 1939.

Between 1776 and 1920, the US Congress designed more than 200 distinct securities and stated the maximum amount of each that the Treasury could sell. Between 1917 and 1939, Congress gradually delegated all decisions about designing US debt instruments to the Treasury. In 1939, Congress began imposing a limit on the par value of total federal debt outstanding.

The serine-threonine protein kinase PAK4 is dispensable in zebrafish: identification of a morpholino-generated pseudophenotype.

TALEN-based inactivation of the zebrafish pak4 gene resulted in embryos and adult fish that appear normal and fertile. This is in contrast to our previously published studies which were based on the use of antisense morpholino oligonucleotides (MOs). We have excluded potential explanations such as gene duplication, alternate splicing, cryptic initiation of translation, and translation-independent RNA function.

Maternal pak4 expression is required for primitive myelopoiesis in zebrafish.

Transcripts of pak4, the zebrafish ortholog of p21-activated kinase 4 (PAK4), are most abundant in the egg and fall to low levels by the end of gastrulation, after which expression is essentially ubiquitous. Translation of maternal mRNA into pak4 protein is first detectable at high stage (3.3hpf).

Generation and characterization of a novel neural crest marker allele, Inka1-LacZ, reveals a role for Inka1 in mouse neural tube closure.

Previous studies identified Inka1 as a gene regulated by AP-2alpha in the neural crest required for craniofacial morphogenesis in fish and frog. Here, we extend the analysis of Inka1 function and regulation to the mouse by generating a LacZ knock-in allele. Inka1-LacZ allele expression occurs in the cephalic mesenchyme, heart, and paraxial mesoderm prior to E8.

Myosin-X is required for cranial neural crest cell migration in Xenopus laevis.

Myosin-X (MyoX) belongs to a large family of unconventional, nonmuscle, actin-dependent motor proteins. We show that MyoX is predominantly expressed in cranial neural crest (CNC) cells in embryos of Xenopus laevis and is required for head and jaw cartilage development. Knockdown of MyoX expression using antisense morpholino oligonucleotides resulted in retarded migration of CNC cells into the pharyngeal arches, leading to subsequent hypoplasia of cartilage and inhibited outgrowth of the CNC-derived trigeminal nerve.

Inca: a novel p21-activated kinase-associated protein required for cranial neural crest development.

Inca (induced in neural crest by AP2) is a novel protein discovered in a microarray screen for genes that are upregulated in Xenopus embryos by the transcriptional activator protein Tfap2a. It has no significant similarity to any known protein, but is conserved among vertebrates. In Xenopus, zebrafish and mouse embryos, Inca is expressed predominantly in the premigratory and migrating neural crest (NC).

PCNS: a novel protocadherin required for cranial neural crest migration and somite morphogenesis in Xenopus.

Protocadherins (Pcdhs), a major subfamily of cadherins, play an important role in specific intercellular interactions in development. These molecules are characterized by their unique extracellular domain (EC) with more than 5 cadherin-like repeats, a transmembrane domain (TM) and a variable cytoplasmic domain. PCNS (Protocadherin in Neural crest and Somites), a novel Pcdh in Xenopus, is initially expressed in the mesoderm during gastrulation, followed by expression in the cranial neural crest (CNC) and somites.

Msx1 and Msx2 have shared essential functions in neural crest but may be dispensable in epidermis and axis formation in Xenopus.

The homeodomain factors Msx1 and Msx2 are expressed in essentially identical patterns in the epidermis and neural crest of Xenopus embryos during neurula stages. Disruption of Msx1 and Msx2 RNA splicing with antisense morpholino oligonucleotides shows that both factors are also required for expression of the neural crest gene Slug. Loss of Msx1 can be compensated by overexpression of Msx2 and vice versa.

Expression of TFAP2beta and TFAP2gamma genes in Xenopus laevis.

The embryonic expression patterns of two additional members of the transcription factor TFAP2 family in Xenopus laevis, TFAP2beta and TFAP2gamma, are described. Both genes share overlapping expression domains with the previously characterized TFAP2alpha in this species, although differences exist. All three genes are expressed in the neural crest (NC) region at late gastrula to early neurula stages.

Developmental expression of Xenopus fragile X mental retardation-1 gene.

Dysregulation of Fragile X mental retardation-1 (Fmr1) gene expression results in an inherited form of mental retardation known as the Fragile X syndrome (FXS). Fmr1 is a highly conserved gene with a broad yet distinctive expression pattern during vertebrate development. Here, we examined the expression pattern of Fmr1 during Xenopus embryonic development.

Regulatory targets for transcription factor AP2 in Xenopus embryos.

The transcription factor AP2 (TFAP2) has an important role in regulating gene expression in both epidermis and neural crest cells. In order to further characterize these functions we have used a hormone inducible TFAP2alpha fusion protein in a Xenopus animal cap assay to identify downstream targets of this factor. The most common pattern comprised genes predominantly expressed in the epidermis.

AP-2alpha selectively regulates fragile X mental retardation-1 gene transcription during embryonic development.

Fragile X syndrome (FXS) is almost always caused by silencing of the FMR1 gene. The defects observed in FXS indicate that the normal FMR1 gene has a range of functions and plays a particularly prominent role during development. However, the mechanisms regulating FMR1 expression in vivo are not known.

Specification of the otic placode depends on Sox9 function in Xenopus.

The vertebrate inner ear develops from a thickening of the embryonic ectoderm, adjacent to the hindbrain, known as the otic placode. All components of the inner ear derive from the embryonic otic placode. Sox proteins form a large class of transcriptional regulators implicated in the control of a variety of developmental processes.

A novel TBP-interacting zinc finger protein functions in early development of Xenopus laevis.

A zinc finger protein that interacts with Xenopus TATA-binding protein was previously isolated by a yeast two-hybrid screen and found to serve as a transcriptional repressor. The gene was designated the negatively regulating zinc finger protein gene (NZFP). Herein, NZFP was found to be expressed maternally.

Induction of neural crest in Xenopus by transcription factor AP2alpha.

We report experiments with Xenopus laevis, using both intact embryos and ectodermal explants, showing that the transcription factor AP2alpha is positively regulated by bone morphogenetic protein (BMP) and Wnt signaling, and that this activation is an essential step in the induction of neural crest (NC). Ectopic expression of AP2alpha is sufficient to activate high-level expression of NC-specific genes such as Slug and Sox9, which can occur as isolated domains within the neural plate as well as by expansion of endogenous NC territories. AP2alpha also has the property of inducing NC in isolated ectoderm in which Wnt signaling is provided but BMP signaling is minimized by overexpression of chordin.

Transcription factor AP-2 is an essential and direct regulator of epidermal development in Xenopus.

Expression of the Xenopus homolog of the mammalian transcription factor AP-2alpha (XAP-2) is activated throughout the animal hemisphere shortly after the midblastula transition, and becomes restricted to prospective epidermis by the end of gastrulation, under the control of BMP signal modulation. Elevated expression in the future neural crest region begins at this time. Ectopic expression of XAP-2 can restore transcription of epidermal genes in neuralized ectoderm, both in ectodermal explants and in the intact embryo.