Symmetry in levels of axon-axon homophilic adhesion establishes topography in the corpus callosum and development of connectivity between brain hemispheres.

Specific and highly diverse connectivity between functionally specialized regions of the nervous system is controlled at multiple scales, from anatomically organized connectivity following macroscopic axon tracts to individual axon target-finding and synapse formation. Identifying mechanisms that enable entire subpopulations of related neurons to project their axons with regional specificity within stereotyped tracts to form appropriate long-range connectivity is key to understanding brain development, organization, and function. Here, we investigate how axons of the cerebral cortex form precise connections between the two cortical hemispheres via the corpus callosum.

Inter-axonal molecular crosstalk via Lumican proteoglycan sculpts murine cervical corticospinal innervation by distinct subpopulations.

How CNS circuits sculpt their axonal arbors into spatially and functionally organized domains is not well understood. Segmental specificity of corticospinal connectivity is an exemplar for such regional specificity of many axon projections. Corticospinal neurons (CSN) innervate spinal and brainstem targets with segmental precision, controlling voluntary movement.

Crim1 and Kelch-like 14 exert complementary dual-directional developmental control over segmentally specific corticospinal axon projection targeting.

The cerebral cortex executes highly skilled movement, necessitating that it connects accurately with specific brainstem and spinal motor circuitry. Corticospinal neurons (CSN) must correctly target specific spinal segments, but the basis for this targeting remains unknown. In the accompanying report, we show that segmentally distinct CSN subpopulations are molecularly distinct from early development, identifying candidate molecular controls over segmentally specific axon targeting.

Corticospinal neuron subpopulation-specific developmental genes prospectively indicate mature segmentally specific axon projection targeting.

For precise motor control, distinct subpopulations of corticospinal neurons (CSN) must extend axons to distinct spinal segments, from proximal targets in the brainstem and cervical cord to distal targets in thoracic and lumbar spinal segments. We find that developing CSN subpopulations exhibit striking axon targeting specificity in spinal white matter, which establishes the foundation for durable specificity of adult corticospinal circuitry. Employing developmental retrograde and anterograde labeling, and their distinct neocortical locations, we purified developing CSN subpopulations using fluorescence-activated cell sorting to identify genes differentially expressed between bulbar-cervical and thoracolumbar-projecting CSN subpopulations at critical developmental times.

Monitoring Corticocortical Evoked Potentials During Intracranial Vascular Surgery.

Background: Monitoring of corticocortical evoked potentials (CCEPs) during brain tumor surgery of patients under anesthesia was recently reported to be effective in assisting in preservation of speech function. The aim of this study was to investigate whether CCEPs can be reproducibly measured between the frontal and temporal lobes during standard intracranial vascular surgery under general anesthesia; whether dynamic changes in CCEPs caused by reduced focal cerebral blood flow can be measured; and whether CCEPs can be used to monitor speech function, particularly associated with the left side of the brain.

Methods: We monitored CCEPs during 58 vascular surgeries (42 clipping procedures; 15 bypasses, 1 of which overlapped with clipping; and 2 hematoma removals from the left frontal and temporal lobe) at Kashiwaba Neurosurgical Hospital from October 2016 to January 2018.

Unfolding the Folding Problem of the Cerebral Cortex: Movin' and Groovin'.

The development of reproducible folding in the gyrencephalic cerebral cortex is a topic of great interest to neuroscientists. In a recent paper in Cell, del Toro et al. (2017) show that changing the adhesive properties of neurons in the normally lissencephalic mouse cortex leads to the formation of stereotyped folding.

A balancing Akt: How to fine-tune neuronal migration speed.

In the developing mammalian neocortex, newborn neurons produced deep in the brain from neural stem/progenitor cells set out for a long journey to reach their final destination at the brain surface. This process called radial neuronal migration is prerequisite for the formation of appropriate layers and networks in the cortex, and its dysregulation has been implicated in cortical malformation and neurological diseases. Considering a fine correlation between temporal order of cortical neuronal cell types and their spatial distribution, migration speed needs to be tightly controlled to achieve correct neocortical layering, although the underlying molecular mechanisms remain not fully understood.

PDK1-Akt pathway regulates radial neuronal migration and microtubules in the developing mouse neocortex.

Neurons migrate a long radial distance by a process known as locomotion in the developing mammalian neocortex. During locomotion, immature neurons undergo saltatory movement along radial glia fibers. The molecular mechanisms that regulate the speed of locomotion are largely unknown.

High mobility group nucleosome-binding family proteins promote astrocyte differentiation of neural precursor cells.

Astrocytes are the most abundant cell type in the mammalian brain and are important for the functions of the central nervous system. Although previous studies have shown that the STAT signaling pathway or its regulators promote the generation of astrocytes from multipotent neural precursor cells (NPCs) in the developing mammalian brain, the molecular mechanisms that regulate the astrocytic fate decision have still remained largely unclear. Here, we show that the high mobility group nucleosome-binding (HMGN) family proteins, HMGN1, 2, and 3, promote astrocyte differentiation of NPCs during brain development.

Tcf3 represses Wnt-β-catenin signaling and maintains neural stem cell population during neocortical development.

During mouse neocortical development, the Wnt-β-catenin signaling pathway plays essential roles in various phenomena including neuronal differentiation and proliferation of neural precursor cells (NPCs). Production of the appropriate number of neurons without depletion of the NPC population requires precise regulation of the balance between differentiation and maintenance of NPCs. However, the mechanism that suppresses Wnt signaling to prevent premature neuronal differentiation of NPCs is poorly understood.

Transcriptional coupling of neuronal fate commitment and the onset of migration.

During mammalian CNS development, when the neural precursor cells commit to the neuronal fate they must delaminate and migrate toward the pial surface in order to reach the appropriate final location. Thus, the coordination of delamination and fate commitment is important in creating the correct structure. Although previous studies have proposed that spindle orientation during mitosis plays a role in both delamination and fate commitment, thus coordinating these events, subsequent studies have challenged this model.

Scratch regulates neuronal migration onset via an epithelial-mesenchymal transition-like mechanism.

During neocortical development, the neuroepithelial or neural precursor cells that commit to neuronal fate need to delaminate and start migration toward the pial surface. However, the mechanism that couples neuronal fate commitment to detachment from the neuroepithelium remains largely unknown. Here we show that Scratch1 and Scratch2, members of the Snail superfamily of transcription factors, are expressed upon neuronal fate commitment under the control of proneural genes and promote apical process detachment and radial migration in the developing mouse neocortex.

PDK1 regulates the generation of oligodendrocyte precursor cells at an early stage of mouse telencephalic development.

During the development of the mouse telencephalon, multipotent neural precursor cells (NPCs) generate oligodendrocyte precursor cells (OPCs), progenitors restricted to the oligodendrocyte lineage, at various sites in a developmental stage-dependent manner. Although substantial progress has been made in identifying the transcription factors that control the production of OPCs, the signaling pathways that regulate these transcription factors and the spatiotemporal pattern of OPC production have been only partially clarified. Here, we show that the serine-threonine kinase 3-phosphoinositide-dependent kinase 1 (PDK1) contributes to an early wave of OPC production in the developing mouse telencephalon.

α2-chimaerin controls neuronal migration and functioning of the cerebral cortex through CRMP-2.

Disrupted cortical neuronal migration is associated with epileptic seizures and developmental delay. However, the molecular mechanism by which disruptions of early cortical development result in neurological symptoms is poorly understood. Here we report α2-chimaerin as a key regulator of cortical neuronal migration and function.

Deamination role of inducible glutamate dehydrogenase isoenzyme 7 in Brassica napus leaf protoplasts.

Glutamate dehydrogenase (GDH) is a ubiquitous enzyme that catalyzes the reversible amination of 2-oxoglutarate to glutamate. In Brassica napus, GDH isoenzymes 1 and 7 are hexamers of β and α subunits, respectively and the isoenzyme profile in leaves is known to change on wounding. Here, parallels were sought between the effects of wounding and protoplast isolation because of the possible relevance of changes in GDH activity to the perturbed metabolism in recalcitrant B.

Selective induction of neocortical GABAergic neurons by the PDK1-Akt pathway through activation of Mash1.

Extracellular stimuli regulate neuronal differentiation and subtype specification during brain development, although the intracellular signaling pathways that mediate these processes remain largely unclear. We now show that the PDK1-Akt pathway regulates differentiation of telencephalic neural precursor cells (NPCs). Active Akt promotes differentiation of NPC into gamma-aminobutyric acid-containing (GABAergic) but not glutamatergic neurons.

Double-chambered right ventricle associated with infective endocarditis complication of the pulmonary valve: surgical management.

Double-chambered right ventricle (DCRV) is a rare congenital heart disease characterized by the presence of anomalous muscle bundles, which divide the right ventricle into two chambers: a high-pressure proximal chamber and a low-pressure distal chamber. Most DCRV patients are diagnosed and treated during childhood, and presentation in adulthood is not common. Many congenital heart diseases are often associated with other complications such as infective endocarditis (IE).

The cyclin-dependent kinase inhibitors p57 and p27 regulate neuronal migration in the developing mouse neocortex.

Neuronal precursors remain in the proliferative zone of the developing mammalian neocortex until after they have undergone neuronal differentiation and cell cycle arrest. The newborn neurons then migrate away from the proliferative zone and enter the cortical plate. The molecules that coordinate migration with neuronal differentiation have been unclear.

A novel ATX-S10(Na) photodynamic therapy for human skin tumors and benign hyperproliferative skin.

Background/purpose: Photodynamic therapy (PDT) is a promising treatment for various skin tumors and other skin diseases. We investigated the potential therapeutic effects of PDT using ATX-S10(Na) ointment and a diode laser in mouse skin models of experimental skin tumors as well as transplanted human samples of superficial skin tumors and lesional psoriatic skin.

Methods: ATX-S10(Na) ointment (1% w/v) was introduced into tape-stripped mouse skin, transplanted squamous cell carcinoma (SCC) samples and human skin diseases after topical application, then PDT was performed.

The Wnt/beta-catenin pathway directs neuronal differentiation of cortical neural precursor cells.

Neural precursor cells (NPCs) have the ability to self-renew and to give rise to neuronal and glial lineages. The fate decision of NPCs between proliferation and differentiation determines the number of differentiated cells and the size of each region of the brain. However, the signals that regulate the timing of neuronal differentiation remain unclear.

Primary signet ring cell carcinoma of the prostate: report and review of 42 cases.

We report a case of primary signet ring cell carcinoma of the prostate in a 75-year-old man. Serum prostate specific antigen (PSA) level at presentation was 9.3 ng/mL.

Activation of two caspase cascades, caspase 8/3/6 and caspase 9/3/6, during photodynamic therapy using a novel photosensitizer, ATX-S10(Na), in normal human keratinocytes.

Background/purpose: Photodynamic therapy (PDT) is a potent treatment for skin tumors. Although the therapeutic effect of PDT is supposed to be due to cellular cytotoxicity, the precise mechanism is still unknown. ATX-S10(Na) [13,17-bis(1-carboxypropionyl)carbamoylethyl-8-ethenyl-2-hydroxy-3-hydroxyiminoethylidene-2,7,12,18-tetramethylporphyrin sodium salt], a novel hydrophilic chlorin photosensitizer, shows good accumulation in tumors and is suitable for use in PDT.

Desmoid tumor in a scar from radical nephrectomy for renal cancer.

Desmoid tumor is a fibroblastic proliferation arising in musculoaponeurotic tissues. We report a case of abdominal desmoid tumor discovered 2 years after radical nephrectomy for right renal cell carcinoma. Surgical extirpation was performed and the patient remained well 2 years later with no evidence of disease.

Effects of type of cognitive demand on bilateral advantage in interhemispheric processing.

The relationship between cognitive task demand and effect of bilateral advantage (BLA) was examined. In Experiment 1, the task demand based upon visual stimulus complexity was manipulated. One-digit and two-digit numbers were presented in the left, right or both visual fields tachistoscopically and subjects were requested to identify the numbers.