Reply to Comments of Bassi, Ghirardi, and Tumulka on the Free Will Theorem

We show that the authors in the title have erred in claiming that our axiom FIN is false by conflating it with Bell locality. We also argue that the predictions of quantum mechanics, and in particular EPR, are fully Lorentz invariant, whereas the Free Will Theorem shows that theories with a mechanism of reduction, such as GRW, cannot be made fully invariant.Comment: We sharpen our theorem by replacing axiom FIN by a weaker axiom MIN to answer the above authors' objection

Analysis of Uncharacterized mKiaa1211 Expression during Mouse Development and Cardiovascular Morphogenesis

Mammalian Kiaa1211 and Kiaa1211-like are a homologous pair of uncharacterized, highly conserved genes cloned from fetal and adult brain cDNA libraries. Herein we map the in utero spatiotemporal expression of mKiaa1211 and mKiaa1211L mRNA and their expression patterns in postnatal testis, skin, gastrointestinal, and adipose progenitor tissues. Significantly, mKiaa1211 is present throughout the early stages of mouse heart development, particularly in the second heart field (SHF) lineage as it differentiates from mesenchymal cells into cardiomyocytes. We also show that mKiaa1211 is expressed within several early neuronal tissues destined to give rise to central, peripheral, and sympathetic nervous system structures. Expression profiling revealed that the paralog mKiaa1211L is not expressed during the normal developmental process and that mKiaa1211 expression was noticeably absent from most adult terminally differentiated tissues. Finally, we confirm that a previously uncharacterized CRISPR/CAS-generated mKiaa1211 mouse mutant allele is hypomorphic

Assessment of inhibited alveolar-capillary membrane structural development and function in bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of extreme prematurity and is defined clinically by dependence on supplemental oxygen due to impaired gas exchange. Optimal gas exchange is dependent on the development of a sufficient surface area for diffusion. In the mammalian lung, rapid acquisition of distal lung surface area is accomplished in neonatal and early adult life by means of vascularization and secondary septation of distal lung airspaces. Extreme preterm birth interrupts secondary septation and pulmonary capillary development and ultimately reduces the efficiency of the alveolar-capillary membrane. Although pulmonary health in BPD infants rapidly improves over the first few years, persistent alveolar-capillary membrane dysfunction continues into adolescence and adulthood. Preventative therapies have been largely ineffective, and therapies aimed at promoting normal development of the air-blood barrier in infants with established BPD remain largely unexplored. The purpose of this review will be: (1) to summarize the histological evidence of aberrant alveolar-capillary membrane development associated with extreme preterm birth and BPD, (2) to review the clinical evidence assessing the long-term impact of BPD on alveolar-capillary membrane function, and (3) to discuss the need to develop and incorporate direct measurements of functional gas exchange into clinically relevant animal models of inhibited alveolar development

Origin, development, and differentiation of cardiac fibroblasts

Cardiac fibroblasts are the most abundant cell in the mammalian heart. While they have been historically underappreciated in terms of their functional contributions to cardiac development and physiology, they and their activated form, myofibroblasts, are now known to play key roles in both development and disease through structural, paracrine, and electrical interactions with cardiomyocytes. The lack of specific markers for fibroblasts currently convolutes the study of this dynamic cell lineage, but advances in marker analysis and lineage mapping technologies are continuously being made. Understanding how to best utilize these tools, both individually and in combination, will help to elucidate the functional significance of fibroblast-cardiomyocyte interactions in vivo. Here we review what is currently known about the diverse roles played by cardiac fibroblasts and myofibroblasts throughout development and periods of injury with the intent of emphasizing the duality of their nature

Rib Truncations and Fusions in the Sp2HMouse Reveal a Role for Pax3 in Specification of the Ventro-lateral and Posterior Parts of the Somite

AbstractThesplotch (Pax3)mouse mutant serves as a model for developmental defects of several types, including defective migration of dermomyotomal cells to form the limb musculature. Here, we describe abnormalities of the ribs, neural arches, and acromion inSp2Hhomozygous embryos, indicating a widespread dependence of lateral somite development onPax3function. Moreover, the intercostal and body wall muscles, derivatives of the ventrolateral myotome, are also abnormal inSp2Hhomozygotes.Pax3is expressed in the dermomyotome, but not in either the sclerotome or the myotome, raising the possibility thatPax3-dependent inductive influences from the dermomyotome are necessary for early specification of lateral sclerotome and myotome. Support for this idea comes from analysis of gene expression markers of lateral sclerotome (tenascin-Candscleraxis) and myotome (myogenin, MyoD,andMyf5). All exhibit ventrally truncated domains of expression inSp2Hhomozygotes, potentially accounting for the rib and intercostal muscle truncations. In contrast, the medial sclerotomal markerPax1is expressed normally in mutant embryos, arguing thatPax3is not required for development of the medial sclerotome. Most of the somitic markers show ectopic expression in anteroposterior and mediolateral dimensions, suggesting a loss of definition of somite boundaries insplotchand explaining the rib and muscle fusions. An exception isMyf5,which is not ectopically expressed inSp2Hhomozygotes, consistent with the previous suggestion thatPax3andMyf5function in different pathways of skeletal myogenesis. PDGFα and its receptor are candidates for mediating signalling between myotome and sclerotome. We find that both genes are misexpressed inSp2Hembryos, suggesting that PDGFα/PDGFRα may function downstream ofPax3,accounting for the close similarities between thesplotchandPatchmutant phenotypes. Our findings point to additional regulatory functions for the Pax3 transcription factor, apart from those already demonstrated for development of the neural tube, neural crest, and dermomyotome

The Influence of Stock Market Listing on Human Resource Managment: Evidence for France and Britain

We use data from REPONSE 2004 and WERS 2004 to analyse whether approaches to HRM differ according to whether an establishment is part of a company with a stock exchange listing. In both countries we find that listing is positively associated with teamworking and performance-related pay, while in France, but not in Britain, it is also linked to worker autonomy and training. Our findings are inconsistent with the claim that shareholder pressure operates as a constraint on the adoption of high-performance workplace practices. The pattern is similar in the two countries, but with a slightly stronger tendency for listing to be associated with high-performance workplace practices in France.corporate governance, human resource management, employment relations

Periostin as a Heterofunctional Regulator of Cardiac Development and Disease

Periostin (Postn) is a heterofunctional secreted extracellular matrix (ECM) protein comprised of four fasciclin domains that promotes cellular adhesion and movement, as well as collagen fibrillogenesis. Postn is expressed in unique growth centers during embryonic development where it facilitates epithelial-mesenchymal transition (EMT) of select cell populations undergoing reorganization. In the heart, Postn is expressed in the developing valves, cardiac fibroblasts and in regions of the outflow track. In the adult, Postn expression is specifically induced in areas of tissue injury or areas with ongoing cellular re-organization. In the adult heart Postn is induced in the ventricles following myocardial infarction, pressure overload stimulation, or generalized cardiomyopathy. Here we will review the functional consequences associated with Postn induction in both the developing and adult heart. The majority of data collected to date suggest a common function for Postn in both development and disease as a potent inducible regulator of cellular reorganization and extracellular matrix homeostasis, although some alternate and controversial functions have also been ascribed to Postn, the validity of which will be discussed here

Phosphoregulation of Twist1 Provides a Mechanism of Cell Fate Control

Basic Helix-loop-Helix (bHLH) factors play a significant role in both development and disease. bHLH factors function as protein dimers where two bHLH factors compose an active transcriptional complex. In various species, the bHLH factor Twist has been shown to play critical roles in diverse developmental systems such as mesoderm formation, neurogenesis, myogenesis, and neural crest cell migration and differentiation. Pathologically, Twist1 is a master regulator of epithelial-to-mesenchymal transition (EMT) and is causative of the autosomal-dominant human disease Saethre Chotzen Syndrome (SCS). Given the wide spectrum of Twist1 expression in the developing embryo and the diverse roles it plays within these forming tissues, the question of how Twist1 fills some of these specific roles has been largely unanswered. Recent work has shown that Twist’s biological function can be regulated by its partner choice within a given cell. Our work has identified a phosphoregulatory circuit where phosphorylation of key residues within the bHLH domain alters partner affinities for Twist1; and more recently, we show that the DNA binding affinity of the complexes that do form is affected in a cis-element dependent manner. Such perturbations are complex as they not only affect direct transcriptional programs of Twist1, but they indirectly affect the transcriptional outcomes of any bHLH factor that can dimerize with Twist1. Thus, the resulting lineage-restricted cell fate defects are a combination of loss-of-function and gain-of-function events. Relating the observed phenotypes of defective Twist function with this complex regulatory mechanism will add insight into our understanding of the critical functions of this complex transcription factor

Special Issue “2020 Feature Papers by JDB’ Editorial Board Members”

For this Special Issue "2020 Feature Papers by JDB' Editorial Board Members," we present a collection of studies, including original research papers, and review articles by our distinguished editorial board members that focus on advances in understanding multicellular organisms' growth, differentiation, and remodeling [...]