Do nonfinancial firms hold risky financial assets? Evidence from Germany

Recent empirical evidence suggests that US industrial firms invest heavily in noncash, risky financial assets. Using hand-collected data on financial portfolios of German firms, we show that risky asset holdings are not an anomaly unique to the US. We find that industrial firms in Germany invest 11.6% of their financial assets in noncash and risky assets. Value-weighted, this percentage increases to 25.4 %. While the equally-weighted average is substantial, it is clearly lower (5 percentage points or 30% in relative terms) than that in the US. After accounting for cross-country compositional differences (especially the dominance of large firms in the US technologysector), this difference in risky financial asset holdings decreases but remains at 3 percentage points. The remaining difference is driven by institutional differences that affect the relationship between firm characteristics and risky financial asset holdings in the two countries. In contrast to the US, German firms largely follow the precautionary savings motive and do not seem to misappropriate their funds when shifting them towards riskier asset allocations. Our results have implications for how asset management by nonfinancial firms should be regulated

Axin2 as regulatory and therapeutic target in newborn brain injury and remyelination.

Permanent damage to white matter tracts, comprising axons and myelinating oligodendrocytes, is an important component of brain injuries of the newborn that cause cerebral palsy and cognitive disabilities, as well as multiple sclerosis in adults. However, regulatory factors relevant in human developmental myelin disorders and in myelin regeneration are unclear. We found that AXIN2 was expressed in immature oligodendrocyte progenitor cells (OLPs) in white matter lesions of human newborns with neonatal hypoxic-ischemic and gliotic brain damage, as well as in active multiple sclerosis lesions in adults. Axin2 is a target of Wnt transcriptional activation that negatively feeds back on the pathway, promoting β-catenin degradation. We found that Axin2 function was essential for normal kinetics of remyelination. The small molecule inhibitor XAV939, which targets the enzymatic activity of tankyrase, acted to stabilize Axin2 levels in OLPs from brain and spinal cord and accelerated their differentiation and myelination after hypoxic and demyelinating injury. Together, these findings indicate that Axin2 is an essential regulator of remyelination and that it might serve as a pharmacological checkpoint in this process

Hedgehog signalling in gut development, physiology and cancer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90081/1/jphysiol.2011.220681.pd

Dynamic touch reduces physiological arousal in preterm infants: A role for c-tactile afferents?

Preterm birth is a significant risk factor for a range of long-term health problems and developmental disabilities. Though touch plays a central role in many perinatal care strategies, the neurobiological basis of these approaches is seldom considered. C-Tactile afferents (CTs) are a class of unmyelinated nerve fibre activated by low force, dynamic touch. Consistent with an interoceptive function, touch specifically targeted to activate CTs activates posterior insular cortex and has been reported to reduce autonomic arousal. The present study compared the effect of 5 min of CT optimal velocity stroking touch to 5 min of static touch on the heart-rate and oxygen saturation levels of preterm infants between 28- & 37-weeks gestational age. CT touch produced a significant decrease in infants' heart-rates and increase in their blood oxygenation levels, which sustained throughout a 5-min post-touch period. In contrast, there was no significant change in heart-rate or blood oxygenation levels of infants receiving static touch. These findings provide support for the hypothesis that CTs signal the affective quality of nurturing touch, providing a neurobiological substrate for the apparent beneficial effects of neonatal tactile interventions and offering insight for their optimisation

Gi/o-protein coupled receptors in the aging brain

Cells translate extracellular signals to regulate processes such as differentiation, metabolism and proliferation, via transmembranar receptors. G protein-coupled receptors (GPCRs) belong to the largest family of transmembrane receptors, with over 800 members in the human species. Given the variety of key physiological functions regulated by GPCRs, these are main targets of existing drugs. During normal aging, alterations in the expression and activity of GPCRs have been observed. The central nervous system (CNS) is particularly affected by these alterations, which results in decreased brain functions, impaired neuroregeneration, and increased vulnerability to neuropathologies, such as Alzheimer's and Parkinson diseases. GPCRs signal via heterotrimeric G proteins, such as Go, the most abundant heterotrimeric G protein in CNS. We here review age-induced effects of GPCR signaling via the Gi/o subfamily at the CNS. During the aging process, a reduction in protein density is observed for almost half of the Gi/o-coupled GPCRs, particularly in age-vulnerable regions such as the frontal cortex, hippocampus, substantia nigra and striatum. Gi/o levels also tend to decrease with aging, particularly in regions such as the frontal cortex. Alterations in the expression and activity of GPCRs and coupled G proteins result from altered proteostasis, peroxidation of membranar lipids and age-associated neuronal degeneration and death, and have impact on aging hallmarks and age-related neuropathologies. Further, due to oligomerization of GPCRs at the membrane and their cooperative signaling, down-regulation of a specific Gi/o-coupled GPCR may affect signaling and drug targeting of other types/subtypes of GPCRs with which it dimerizes. Gi/o-coupled GPCRs receptorsomes are thus the focus of more effective therapeutic drugs aiming to prevent or revert the decline in brain functions and increased risk of neuropathologies at advanced ages.This work was supported by Fundação para a Ciência e Tecnologia, Centro 2020 and Portugal 2020, the COMPETE program, QREN, and the European Union (FEDER program) via the GoBack project (PTDC/CVT-CVT/32261/2017), the pAGE program (Centro-01-0145-FEDER-000003), and Institute for Biomedicine iBiMED (UID/BIM/04501/2013; UID/BIM/04501/2019).publishe

Transcriptional Mechanisms of Oligodendrocyte Development and Their Response to Hypoxia

Oligodendrocytes are the myelinating cells of the central nervous system (CNS). By enabling rapid nerve conduction and in turn the dense packing of relatively small-bore axons into white matter tracts, myelination was essential for the evolution of the complex vertebrate brain. Permanent dysmyelination of the CNS is a central component of injuries that cause cerebral palsy and cognitive disabilities, as well as Multiple Sclerosis. The factors that instruct oligodendrocyte specification, proliferation, maturation and their ultimate matching to axonal partners is thus an essential question of both basic and clinical neuroscience. My dissertation focuses on two distinct transcriptional mechanisms that respectively regulate: (1) the initial allocation oligodendrocytes from multipotent progenitors and (2) the onset of oligodendrocyte maturation and myelination. I first demonstrate that the bHLH transcription factor Olig1 is expressed in radial glia of the ventral telencephalon. Olig1 promotes production of oligodendrocytes and represses production of GABAergic interneurons throughout the mouse brain. Olig1 deletion in mutant mice results in ectopic expression and upregulation of Dlx1/2 genes in the ventral medial ganglionic eminences and adjacent regions of the septum resulting in a ~30% increase in adult cortical interneuron numbers with corresponding diminution of oligodendrocyte lineage cells in the embryo and adult. I show that Olig1 directly represses the Dlx1/2 I12b intergenic enhancer and that Dlx1/2 functions genetically downstream of Olig1. I find that Olig1 is likewise responsible for neuron versus oligodendrocyte specification during repair phases of forebrain Hypoxic-ischemic encephalopathy. These findings build on previous studies that suggest there is common origin of oligodendrocytes and interneurons in the telencephalon. They further establish Olig1 as an essential repressor of Dlx1/2 and interneuron production in developing mammalian brain.In a second set of studies, I have investigated roles for Hypoxia Inducible Factors (HIFs) in regulating oligodendrocyte ontogeny. Though, HIFs are largely dispensable for oligodendrocyte specification, they are essential regulators of postnatal oligodendrocyte maturation. This work has also elucidated a surprising cell intrinsic role for oligodendrocytes in the coordination of myelination and white matter angiogenesis. Here I show that O2 tension, mediated by OPC-encoded Hypoxia-inducible factor (HIF) function, is an essential regulator of postnatal myelination. Constitutive HIF1/2α stabilization resulted in OPC maturation arrest through autocrine activation of canonical Wnt7a/7b. Surprisingly, such OPCs also show paracrine activity that induces excessive postnatal white matter angiogenesis in vivo, and directly stimulates endothelial cell proliferation in vitro. Conversely, OPC-specific HIF1/2α loss-of-function leads to insufficient angiogenesis in corpus callosum and catastrophic axon loss. These findings establish that OPC-intrinsic HIF signaling is essential for postnatal white matter angiogenesis and for synchronizing vascularization with the onset of myelination in the mammalian brain. Taken together these studies reveal novel transcriptional mechanisms involved in broad aspects of oligodendrocyte ontogeny, which play overlapping roles in the pathophysiology of developmental white matter injury