Calcium dynamics at the neural cell primary cilium regulate Hedgehog signaling-dependent neurogenesis in the embryonic neural tube.

The balance between neural stem cell proliferation and neuronal differentiation is paramount for the appropriate development of the nervous system. Sonic hedgehog (Shh) is known to sequentially promote cell proliferation and specification of neuronal phenotypes, but the signaling mechanisms responsible for the developmental switch from mitogenic to neurogenic have remained unclear. Here, we show that Shh enhances Ca activity at the neural cell primary cilium of developing embryos through Ca influx via transient receptor potential cation channel subfamily C member 3 (TRPC3) and release from intracellular stores in a developmental stage-dependent manner.

Signal amplification in growth cone gradient sensing by a double negative feedback loop among PTEN, PI(3,4,5)P and actomyosin.

Axon guidance during neural wiring involves a series of precisely controlled chemotactic events by the motile axonal tip, the growth cone. A fundamental question is how neuronal growth cones make directional decisions in response to extremely shallow gradients of guidance cues with exquisite sensitivity. Here we report that nerve growth cones possess a signal amplification mechanism during gradient sensing process.

Growth at Cold Temperature Increases the Number of Motor Neurons to Optimize Locomotor Function.

During vertebrate development, spinal neurons differentiate and connect to generate a system that performs sensorimotor functions critical for survival. Spontaneous Ca activity regulates different aspects of spinal neuron differentiation. It is unclear whether environmental factors can modulate this Ca activity in developing spinal neurons to alter their specialization and ultimately adjust sensorimotor behavior to fit the environment.

A successful management after preterm delivery in a patient with severe sepsis during third-trimester pregnancy.

A 33-year-old woman visited the emergency department presenting with fever and dyspnea. She was pregnant with gestational age of 31 weeks and 6 days. She had dysuria for 7 days, and fever and dyspnea for 1 day.

Rapid Response Systems Reduce In-Hospital Cardiopulmonary Arrest: A Pilot Study and Motivation for a Nationwide Survey.

Background: Early recognition of the signs and symptoms of clinical deterioration could diminish the incidence of cardiopulmonary arrest. The present study investigates outcomes with respect to cardiopulmonary arrest rates in institutions with and without rapid response systems (RRSs) and the current level of cardiopulmonary arrest rate in tertiary hospitals.

Methods: This was a retrospective study based on data from 14 tertiary hospitals.

The Many Hats of Sonic Hedgehog Signaling in Nervous System Development and Disease.

Sonic hedgehog (Shh) signaling occurs concurrently with the many processes that constitute nervous system development. Although Shh is mostly known for its proliferative and morphogenic action through its effects on neural stem cells and progenitors, it also contributes to neuronal differentiation, axonal pathfinding and synapse formation and function. To participate in these diverse events, Shh signaling manifests differently depending on the maturational state of the responsive cell, on the other signaling pathways regulating neural cell function and the environmental cues that surround target cells.

Comparison of intubation times using a manikin with an immobilized cervical spine: Macintosh laryngoscope vs. GlideScope vs. fiberoptic bronchoscope.

Objective: Airway management in patients with suspected cervical spine injury is classified as a "difficult airway." The best device for managing difficult airways is not known. Therefore, we conducted an intubation study simulating patients with cervical spine injury using three devices: a conventional Macintosh laryngoscope, a video laryngoscope (GlideScope), and a fiberoptic bronchoscope (MAF-TM).

Spatiotemporal integration of developmental cues in neural development.

Nervous system development relies on the generation of neurons, their differentiation and establishment of synaptic connections. These events exhibit remarkable plasticity and are regulated by many developmental cues. Here, we review the mechanisms of three classes of these cues: morphogenetic proteins, electrical activity, and the environment.

A critical role for STIM1 in filopodial calcium entry and axon guidance.

Background: Stromal interaction molecule 1 (STIM1), a Ca2+ sensor in the endoplasmic reticulum, regulates store-operated Ca2+ entry (SOCE) that is essential for Ca2+ homeostasis in many types of cells. However, if and how STIM1 and SOCE function in nerve growth cones during axon guidance remains to be elucidated.

Results: We report that STIM1 and transient receptor potential channel 1 (TRPC1)-dependent SOCE operates in Xenopus spinal growth cones to regulate Ca2+ signaling and guidance responses.

Dynamic localization of G-actin during membrane protrusion in neuronal motility.

Background: Actin-based cell motility is fundamental for development, function, and malignant events in eukaryotic organisms. During neural development, axonal growth cones depend on rapid assembly and disassembly of actin filaments (F-actin) for their guided extension to specific targets for wiring. Monomeric globular actin (G-actin) is the building block for F-actin but is not considered to play a direct role in spatiotemporal control of actin dynamics in cell motility.

Path integral Monte Carlo with importance sampling for excitons interacting with an arbitrary phonon bath.

The reduced density matrix of excitons coupled to a phonon bath at a finite temperature is studied using the path integral Monte Carlo method. Appropriate choices of estimators and importance sampling schemes are crucial to the performance of the Monte Carlo simulation. We show that by choosing the population-normalized estimator for the reduced density matrix, an efficient and physically-meaningful sampling function can be obtained.

Atomistic study of the long-lived quantum coherences in the Fenna-Matthews-Olson complex.

A remarkable amount of theoretical research has been carried out to elucidate the physical origins of the recently observed long-lived quantum coherence in the electronic energy transfer process in biological photosynthetic systems. Although successful in many respects, several widely used descriptions only include an effective treatment of the protein-chromophore interactions. In this work, by combining an all-atom molecular dynamics simulation, time-dependent density functional theory, and open quantum system approaches, we successfully simulate the dynamics of the electronic energy transfer of the Fenna-Matthews-Olson pigment-protein complex.

Postsynaptic TRPC1 function contributes to BDNF-induced synaptic potentiation at the developing neuromuscular junction.

Brain-derived neurotrophic factor (BDNF) induces synaptic potentiation at both neuromuscular junctions (NMJs) and synapses of the CNS through a Ca2+ -dependent pathway. The molecular mechanism underlying BDNF-induced synaptic potentiation, especially the regulation of Ca2+ dynamics, is not well understood. Using the Xenopus NMJ in culture as a model system, we show that pharmacological inhibition or morpholino-mediated knockdown of Xenopus TRPC1 (XTRPC1) significantly attenuated the BDNF-induced potentiation of the frequency of spontaneous synaptic responses at the NMJ.

Simplified Sum-Over-States Approach for Predicting Resonance Raman Spectra. Application to Nucleic Acid Bases.

Resonance Raman spectra provide a valuable probe into molecular excited-state structures and properties. Moreover, resonance enhancement is of importance for the chemical contribution to surface-enhanced Raman scattering. In this work, we introduce a simplified sum-over-states scheme for computing Raman spectra and Raman excitation profiles.

Anti-ganglioside antibody-mediated activation of RhoA induces inhibition of neurite outgrowth.

Anti-ganglioside antibodies (Abs) are strongly associated with axonal forms of Guillain Barré syndrome (GBS). Some studies indicate that these Abs, including those with GD1a reactivity, are associated with poor prognosis and/or incomplete recovery. We recently demonstrated that a disease-relevant anti-ganglioside Ab with GD1a reactivity inhibits axon regeneration after PNS injury in an animal model (Lehmann et al.

Peptidyl-prolyl isomerase FKBP52 controls chemotropic guidance of neuronal growth cones via regulation of TRPC1 channel opening.

Immunophilins, including FK506-binding proteins (FKBPs), are protein chaperones with peptidyl-prolyl isomerase (PPIase) activity. Initially identified as pharmacological receptors for immunosuppressants to regulate immune responses via isomerase-independent mechanisms, FKBPs are most highly expressed in the nervous system, where their physiological function as isomerases remains unknown. We demonstrate that FKBP12 and FKBP52 catalyze cis/trans isomerization of regions of TRPC1 implicated in controlling channel opening.

Roles of channels and receptors in the growth cone during PNS axonal regeneration.

Neurons in the peripheral nervous system (PNS) are known to maintain a regenerative capacity and will normally regenerate their axons within a permissive growth environment. The success of regeneration in the PNS largely depends on maintenance of the supportive basal lamina membrane, efficient removal of axonal and myelin debris by macrophages and Schwann cells, expression of neurotrophic factors by Schwann cells, and up-regulation of the intrinsic growth program in PNS neurons. The PNS regenerative process is well characterized through initial Wallerian degeneration followed by axonal sprouting, formation of neuronal growth cones, active axonal growth to the target, and finally sensory and motor functional recovery.

First-principles semiclassical initial value representation molecular dynamics.

In this work, we explore the use of the semiclassical initial value representation (SC-IVR) method with first-principles electronic structure approaches to carry out classical molecular dynamics. The proposed approach can extract the vibrational power spectrum of carbon dioxide from a single trajectory providing numerical results that agree with experiment and quantum calculations. The computational demands of the method are comparable to those of classical single-trajectory calculations, while describing uniquely quantum features such as the zero-point energy and Fermi resonances.

A microfluidics-based turning assay reveals complex growth cone responses to integrated gradients of substrate-bound ECM molecules and diffusible guidance cues.

Neuronal growth cones contain sophisticated molecular machinery precisely regulating their migration in response to complex combinatorial gradients of diverse external cues. The details of this regulation are still largely unknown, in part due to limitations of the currently available experimental techniques. Microfluidic devices have been shown to be capable of generating complex, stable and precisely controlled chemical gradients, but their use in studying growth cone migration has been limited in part due to the effects of shear stress.

Identification and expression of XRTN1-A and XRTN1-C in Xenopus laevis.

Reticulon1, also known as neuroendocrine-specific protein, belongs to the reticulon (RTN) family, whose members possess a conserved reticulon domain and are associated with the endoplasmic reticulum (ER) membrane. Here, we report cloning and expression of Xenopus homologues of Reticulon1-A (XRTN1-A) and -C (XRTN1-C). XRTN1-A and -C contain an open reading frame of 752 and 207 amino acids, respectively, each containing a conserved reticulon domain.

Signaling of secreted semaphorins in growth cone steering.

Despite a tremendous amount of progress in the identification and characterization of many new players as components of class 3 secreted semaphorin signaling in growth cone steering (Fig. 1), our understanding of the molecular mechanisms is far from complete. More questions remain to be answered: how are differential cytoskeletal changes within a growth cone achieved in response to semaphorins? What are the target(s) of cyclic nucleotide modulation? How does a growth cone make a reliable decision in response to a shallow gradient? And finally, how does a growth cone maintain its sensitivity to a decreasing concentration ofsemaphorins when it is growing away from the source? With a high degree of interest in the field with the development of novel technologies in analyzing growth cone steering, we expect to see a much more complete picture of semaphoring signaling in the near future.

BMP gradients steer nerve growth cones by a balancing act of LIM kinase and Slingshot phosphatase on ADF/cofilin.

Bone morphogenic proteins (BMPs) are involved in axon pathfinding, but how they guide growth cones remains elusive. In this study, we report that a BMP7 gradient elicits bidirectional turning responses from nerve growth cones by acting through LIM kinase (LIMK) and Slingshot (SSH) phosphatase to regulate actin-depolymerizing factor (ADF)/cofilin-mediated actin dynamics. Xenopus laevis growth cones from 4-8-h cultured neurons are attracted to BMP7 gradients but become repelled by BMP7 after overnight culture.

Isolation of Xenopus FGF-8b and comparison with FGF-8a.

The Xenopus FGF-8a and FGF-8b isoforms have been reported to be neural crest and neuronal inducers, respectively. However, cloning of Xenopus FGF-8b (XFGF-8b) has not been reported previously and the two isoforms do not seem to have been clearly distinguished in Xenopus experiments. Here, we describe the cloning and expression of XFGF-8b and compare the effects of the two isoforms.

XTRPC1-dependent chemotropic guidance of neuronal growth cones.

Calcium arising through release from intracellular stores and from influx across the plasma membrane is essential for signalling by specific guidance cues and by factors that inhibit axon regeneration. The mediators of calcium influx in these cases are largely unknown. Transient receptor potential channels (TRPCs) belong to a superfamily of Ca2+-permeable, receptor-operated channels that have important roles in sensing and responding to changes in the local environment.