Congenital heart disease (CHD) has, despite significant improvements in patient survival, increasingly become associated with neurological deficits during infancy that persist into adulthood. These ...impairments afflict a wide range of behavioral domains including executive function, motor learning and coordination, social interaction, and language acquisition, reflecting alterations in multiple brain areas. In the past few decades, it has become clear that CHD is highly genetically heterogeneous, with large chromosomal aneuploidies and copy number variants (CNVs) as well as single nucleotide polymorphisms (SNPs) being implicated in CHD pathogenesis. Intriguingly, many of the identified loss-of-function genetic variants occur in genes important for primary cilia integrity and function, hinting at a key role for primary cilia in CHD. Here we review the current evidence for CHD primary cilia associated genetic variants, their independent functions during cardiac and brain development and their influence on behavior. We also highlight the role of environmental exposures in CHD, including stressors such as surgical factors and anesthesia, and how they might interact with ciliary genetic predispositions to determine the final neurodevelopmental outcome. The multifactorial nature of CHD and neurological impairments linked with it will, on one hand, likely necessitate therapeutic targeting of molecular pathways and neurobehavioral deficits shared by disparate forms of CHD. On the other hand, strategies for better CHD patient stratification based on genomic data, gestational and surgical history, and CHD complexity would allow for more precise therapeutic targeting of comorbid neurological deficits.
Elaborating on our previous presentation, where the term dipolar quantization was introduced, we argue here that adopting
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as the ...Hamiltonian instead of
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yields an infinite circumference limit in two-dimensional conformal field theory. The new Hamiltonian leads to dipolar quantization instead of radial quantization. As a result, the new theory exhibits a continuous and strongly degenerated spectrum in addition to the Virasoro algebra with a continuous index. Its Hilbert space exhibits a different inner product than that obtained in the original theory. The idiosyncrasy of this particular Hamiltonian is its relation to the so-called sine-square deformation, which is found in the study of a certain class of quantum statistical systems. The appearance of the infinite circumference explains why the vacuum states of sine-square deformed systems are coincident with those of the respective closed-boundary systems.
Abstract
Every Riemann surface with genus g and n punctures admits a hyperbolic metric, if 2g − 2 + n > 0. Such a surface can be decomposed into pairs of pants whose boundaries are geodesics. We ...construct a string field theory for closed bosonic strings based on this pants decomposition. In order to do so, we derive a recursion relation satisfied by the off-shell amplitudes, using Mirzakhani’s scheme for computing integrals over the moduli space of bordered Riemann surfaces. The recursion relation can be turned into a string field theory via the Fokker–Planck formalism. The Fokker–Planck Hamiltonian consists of kinetic terms and three-string vertices. Unfortunately, the worldsheet BRST symmetry is not manifest in the theory thus constructed. We will show that the invariance can be made manifest by introducing auxiliary fields.
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We study the odd spin structure contributions to the multiloop amplitudes of light-cone gauge superstring field theory. We show that they coincide with the amplitudes in the conformal gauge ...with two of the vertex operators chosen to be in the pictures different from the standard choice, namely (−1, −1) picture in the type II case and −1 picture in the heterotic case. We also show that the contact term divergences can be regularized in the same way as in the amplitudes for the even structures and we get the amplitudes which coincide with those obtained from the first-quantized approach.
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We study profiles and gauge invariant observables of classical solutions corresponding to a constant magnetic field on a torus in open string field theory. We numerically find that the ...profile is not discontinuous on the torus, although the solution describes topologically nontrivial configurations in the context of low energy effective theory. From the gauge invariant observables, we show that the solution provide correct couplings of closed strings to a D-brane with constant magnetic field.
In the past 2 decades, it has become evident that individuals born with congenital heart disease (CHD) are at risk of developing life-long neurological deficits. Multifactorial risk factors ...contributing to neurodevelopmental abnormalities associated with CHD have been identified; however, the underlying causes remain largely unknown, and efforts to address this issue have only recently begun. There has been a dramatic shift in focus from newly acquired brain injuries associated with corrective and palliative heart surgery to antenatal and preoperative factors governing altered brain maturation in CHD. In this review, we describe key time windows of development during which the immature brain is vulnerable to injury. Special emphasis is placed on the dynamic nature of cellular events and how CHD may adversely impact the cellular units and networks necessary for proper cognitive and motor function. In addition, we describe current gaps in knowledge and offer perspectives about what can be done to improve our understanding of neurological deficits in CHD. Ultimately, a multidisciplinary approach will be essential to prevent or improve adverse neurodevelopmental outcomes in individuals surviving CHD.
Highlights • Complex congenital heart disease (CHD) is often associated with developmental delay and behavioral problems. • Currently, the neurological deficits displayed by CHD patients are ...irreversible. • Animal studies offer powerful avenues to understand CHD brain impairments.
The developing brain is under the risk of exposure to a multitude of environmental stressors. While perinatal exposure to excessive levels of environmental stress is responsible for a wide spectrum ...of neurological and psychiatric conditions, the developing brain is equipped with intrinsic cell protection, the mechanisms of which remain unknown. Here we show, using neonatal mouse as a model system, that primary cilia, hair-like protrusions from the neuronal cell body, play an essential role in protecting immature neurons from the negative impacts of exposure to environmental stress. More specifically, we found that primary cilia prevent the degeneration of dendritic arbors upon exposure to alcohol and ketamine, two major cell stressors, by activating cilia-localized insulin-like growth factor 1 receptor and downstream Akt signaling. We also found that activation of this pathway inhibits Caspase-3 activation and caspase-mediated cleavage/fragmentation of cytoskeletal proteins in stress-exposed neurons. These results indicate that primary cilia play an integral role in mitigating adverse impacts of environmental stressors such as drugs on perinatal brain development.
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