The comparison of a novel continuous cardiac output monitor based on pulse wave transit time and echo Doppler during exercise.

A new technology called estimated continuous cardiac output (esCCO) uses pulse wave transit time (PWTT) obtained from an electrocardiogram and pulse oximeter to measure cardiac output (CO) non-invasively and continuously. This study was performed to evaluate the accuracy of esCCO during exercise testing. We compared esCCO with CO measured by the echo Doppler aortic velocity-time integral (VTIao_CO).

Inhibitory and excitatory subtypes of cochlear nucleus neurons are defined by distinct bHLH transcription factors, Ptf1a and Atoh1.

The cochlear nucleus (CN), which consists of dorsal and ventral cochlear nuclei (DCN and VCN), plays pivotal roles in processing and relaying auditory information to the brain. Although it contains various types of neurons, the origins of the distinct subtypes and their developmental molecular machinery are still elusive. Here we reveal that two basic helix-loop-helix transcription factors play crucial roles in specifying neuron subtypes in the CN.

The p21-activated kinase is required for neuronal migration in the cerebral cortex.

The normal formation and function of the mammalian cerebral cortex depend on the positioning of its neurones, which occurs in a highly organized, layer-specific manner. The correct morphology and movement of neurones rely on synchronized regulation of their actin filaments and microtubules. The p21-activated kinase (Pak1), a key cytoskeletal regulator, controls neuronal polarization, elaboration of axons and dendrites, and the formation of dendritic spines.

Reduction of Ptf1a gene dosage causes pancreatic hypoplasia and diabetes in mice.

Objective: Most pancreatic endocrine cells derive from Ptf1a-expressing progenitor cells. In humans, nonsense mutations in Ptf1a have recently been identified as a cause of permanent neonatal diabetes associated with pancreatic agenesis. The death of Ptf1a-null mice soon after birth has not allowed further insight into the pathogenesis of the disease; it is therefore unclear how much pancreatic endocrine function is dependent on Ptf1a in mammals.

Origin of climbing fiber neurons and their developmental dependence on Ptf1a.

Climbing fiber (CF) neurons in the inferior olivary nucleus (ION) extend their axons to Purkinje cells, playing a crucial role in regulating cerebellar function. However, little is known about their precise place of birth and developmental molecular machinery. Here, we describe the origin of the CF neuron lineage and the involvement of Ptf1a (pancreatic transcription factor 1a) in CF neuron development.

Neurabin-I is phosphorylated by Cdk5: implications for neuronal morphogenesis and cortical migration.

The correct morphology and migration of neurons, which is essential for the normal development of the nervous system, is enabled by the regulation of their cytoskeletal elements. We reveal that Neurabin-I, a neuronal-specific F-actin-binding protein, has an essential function in the developing forebrain. We show that gain and loss of Neurabin-I expression affect neuronal morphology, neurite outgrowth, and radial migration of differentiating cortical and hippocampal neurons, suggesting that tight regulation of Neurabin-I function is required for normal forebrain development.

Localized activation of p21-activated kinase controls neuronal polarity and morphology.

In the developing forebrain, neuronal polarization is a stepwise and initially reversible process that underlies correct migration and axon specification. Many aspects of cytoskeletal changes that accompany polarization are currently molecularly undefined and thus poorly understood. Here we reveal that the p21-activated kinase (Pak1) is essential for the specification of an axon and dendrites.

Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum.

The molecular machinery governing glutamatergic-GABAergic neuronal subtype specification is unclear. Here we describe a cerebellar mutant, cerebelless, which lacks the entire cerebellar cortex in adults. The primary defect of the mutant brains was a specific inhibition of GABAergic neuron production from the cerebellar ventricular zone (VZ), resulting in secondary and complete loss of external germinal layer, pontine, and olivary nuclei during development.

Involvement of a Rac activator,P-Rex1, in neurotrophin-derived signaling and neuronal migration.

Rho-family GTPases play key roles in regulating cytoskeletal reorganization, contributing to many aspects of nervous system development. Their activities are known to be regulated by guanine nucleotide exchange factors (GEFs), in response to various extracellular cues. P-Rex1, a GEF for Rac, has been mainly investigated in neutrophils, in which this molecule contributes to reactive oxygen species formation.

Roles of STEF/Tiam1, guanine nucleotide exchange factors for Rac1, in regulation of growth cone morphology.

Rho family GTPases are suggested to be pivotal for growth cone behavior, but regulation of their activities in response to environmental cues remains elusive. Here, we describe roles of STEF and Tiam1, guanine nucleotide exchange factors for Rac1, in neurite growth and growth cone remodeling. We reveal that, in primary hippocampal neurons, STEF/Tiam1 are localized within growth cones and essential for formation of growth cone lamellipodia, eventually contributing to neurite growth.