Recruitment of katanin p60 by phosphorylated NDEL1, an LIS1 interacting protein, is essential for mitotic cell division and neuronal migration

LIS1 is mutated in the human neuronal migration defect lissencephaly and along with NDEL1 (formerly NUDEL) participates in the regulation of cytoplasmic dynein function during neuronal development. Targeted disruption of Ndel1 suggested that NDEL1 could have other molecular targets that regulate microtubule organization for proper neuronal migration. To further understanding the molecular mechanism of LIS1 and lissencephaly, we identified the katanin p60 microtubule-severing protein as an additional molecular target of NDEL1. We demonstrate that phosphorylation of NDEL1 by Cdk5 facilitates interaction between NDEL1 and p60, suggesting that P-NDEL1 regulates the distribution of katanin p60. Abnormal accumulation of p60 in nucleus of Ndel1 null mutants supports an essential role of NDEL1 in p60 regulation. Complete loss of NDEL1 or expression of dominant negative mutants of p60 in migrating neurons results in defective migration and elongation of nuclear-centrosomal distance. Our results suggest that NDEL1 is essential for mitotic cell division and neuronal migration not only via regulation of cytoplasmic dynein function but also by modulation of katanin p60 localization and function.     

A unique role of dynein and nud family proteins in corticogenesis

Heterozygous LIS1 mutations are the most common cause of human lissencephaly, a human neuronal migration defect, and DCX mutations are the most common cause of X‐linked lissencephaly. Lissencephaly is characterized by a smooth cerebral surface, thick cortex and dilated lateral ventricles associated with mental retardation and seizures due to defective neuronal migration. Lissencephaly due to the heterozygous loss of the gene LIS1 is a good example of a haploinsufficiency disorder. LIS1 was deleted or mutated in a large proportion of patients with lissencephaly in a heterozygous fashion. A series of studies discovered that LIS1 is an essential regulator of cytoplasmic dynein. Notably, the role of LIS1 in regulating dynein activity is highly conserved among eukaryotes. In particular, we reported that LIS1 and NDEL1 are essential for dynein transport to the plus‐end of microtubules by kinesin, which is essential to maintain the proper distribution of cytoplasmic dynein within the cell. In addition, we report that mNUDC (mammalian NUDC) interacts with kinesin‐1 and is required for the anterograde transport of a cytoplasmic dynein complex by kinesin‐1. A microtubule organization and motor proteins are further modulated by post‐translational modifications, including phosphorylation and palmitoylation. These modifications share a common pathway with mitotic cell division. For example, Aurora‐A is activated during neurite elongation, and phosphorylates NDEL1, which facilitates microtubule extension into neurite processes. Elucidations of molecular pathways involving neuronal migrations provide us a chance to design a novel strategy for neurological disorder due to defective neuronal migration. For example, inhibition of calpain protects LIS1 from proteolysis resulting in the augmentation of LIS1 levels, which leads to rescue of the phenotypes that are observed in Lis1+/? mice. Endeavoring to address the regulation of the microtubule network and motor proteins will help in understanding not only corticogenesis but neurodegenerative disorders.     

Natural IVF cycles may be desirable for women with repeated failures by stimulated IVF cycles

Purpose Although many reports support stimulated in vitro fertilization, several patients do not respond to it well. Furthermore, stimulated treatment could be associated with reduced ovarian response. We describe three successful cases involving patients of advanced age from whom dominant follicles were retrieved during the natural cycle. Materials and methods All patients had failed to bear children through stimulated in vitro fertilization. In case 1, a follicle was retrieved after a gonadotropin-releasing hormone agonist was used to induce luteinizing hormone surge. In cases 2 and 3, pregnancy was achieved via completely natural cycles. Results One embryo was transferred every 16 cycles. Ongoing pregnancy—defined as pregnancy progressing beyond gestation week 9—was established in three cycles. The patients successfully delivered and had uneventful neonatal courses. Conclusion Mature oocyte retrieval followed by natural rather than stimulated in vitro fertilization might be a potential treatment for patients of advanced age when stimulated in vitro fertilization has been repeatedly unsuccessful. Capsule We describe three successful pregnancies and deliveries achieved via natural IVF cycles: the patients were older than 37 years with repeated failures by stimulated IVF.     

Pneumocephalus caused by failed ventricular tap: case report

OBJECTIVE AND IMPORTANCE: Ventricular tap is one of the most basic and important techniques to neurosurgeon. Brain tap itself usually does not cause symptomatic complication. The authors report an extremely rare complication case of pneumocephalus caused by failed ventricular tap. CLINICAL PRESENTATION AND INTERVENTION: A 79-year-old woman suffered from normal pressure hydrocephalus after subarachnoid hemorrhage (SAH). Ventriculo-peritoneal shunt was performed two month after SAH. In the operation, ventricular taps were failed twice and third tap was successful for ventricular catheterization through the right posterior parietal burr hole. She presented left hemiparesis from three hours after the operation, and her symptom was gradually deteriorated to complete paralysis the next day. Computed tomography scan disclosed the movement of air along the tract of failed ventricular tap from subcortex to internal capsule. CONCLUSION: Failed ventricular tap could cause severe complications. We have to try to perform ventricular tap by only one attempt.     

Transient homonymous hemianopsia due to thrombosis of the confluence of sinuses after occipital transtentorial removal of pineal region tumor

The authors report a case of 74-year-old woman suffering thrombosis of the confluence of sinuses after the left occipital transtentorial removal of a pineal region epidermoid cyst. Four days after the operation, the patient developed left homonymous hemianopsia. Magnetic resonance imaging revealed a venous infarct in the right occipital lobe and magnetic resonance venography disclosed a signal defect of the posterior part of the confluence of sinuses. The patients' neurological symptom recovered soon after anticoagulation treatment, and magnetic resonance venography after the sixth week showed recanalization of the confluence of sinuses. Although it might be rare, thrombosis of the dural sinus should be recognized as a complication of craniotomy.     

Characteristics of left and right scanning in schizophrenia patients using exploratory eye movements: comparison with healthy subjects

To characterize the left and right scanning function and the effect of affection in schizophrenia patients exploratory eye movements as biologic markers were recorded in 44 schizophrenia patients and 72 age-matched healthy controls. The total eye scanning length (TESL) and total number of gaze points (TNGP) in the left and right visual fields were calculated as subjects viewed neutral or affectively charged pictures. TESL of patients was shorter than that of controls when viewing pictures of smiling babies and open circles. TESL of patients was shorter for smiling faces than for crying babies, but TESL of controls was longer for smiling faces than for crying babies. Left TNGP for smiling faces and circles was lower in patients than in controls. In patients, left TNGP for crying babies was higher than for either smiling babies or circles. In controls, left TNGP for smiling babies was higher than crying babies. In patients, left TNGP for smiling babies and circles was smaller than the right TNGP. In controls, left TNGP was larger for smiling than for crying babies. When viewing smiling babies, both TESL and TNGP were negatively correlated with negative symptom scores in patients. Patients' eye movements in the left visual field were clearly different from controls', suggesting that visual cognitive function is impaired in schizophrenia patients. Exploratory eye movements are a useful marker of visual cognitive function, and are a useful tool to evaluate the influence of affection in schizophrenia patients.     

Unusual variant of persistent primitive hypoglossal artery

Here, we present a case of an unusual variant of a persistent primitive hypoglossal artery, which was found incidentally during an examination for a hypertensive thalamic haemorrhage. The anastomotic vessel arose from the external carotid artery and joined the vertebral artery through the hypoglossal canal. The embryology of the anomaly is briefly discussed.     

Intragastric immunization with recombinant Lactobacillus casei expressing flagellar antigen confers antibody-independent protective immunity against Salmonella enterica serovar Enteritidis

A recombinant Lactobacillus casei expressing a flagellar antigen from Salmonella enterica serovar Enteritidis was constructed and evaluated as a mucosal vaccine. Intragastric immunization of the recombinant strain conferred protective immunity against Salmonella infection in mice. This immunization did not result in antigen-specific antibody in either feces or sera but induced the release of IFN-gamma on restimulation of primed lymphocytes ex vivo. The results suggested that the protective efficacy provided by flagellin-expressing L. casei is mainly attributable to cell-mediated immune responses. In addition, an adjuvant-type effect of the antigen delivery system with L. casei was also observed.