Cognitive and neurological outcome of patients in the Dutch pyridoxine-dependent epilepsy (PDE-ALDH7A1) cohort, a cross-sectional study.

BACKGROUND: Pyridoxine monotherapy in PDE-ALDH7A1 often results in adequate seizure control, but neurodevelopmental outcome varies. Detailed long-term neurological outcome is unknown. Here we present the cognitive and neurological features of the Dutch PDE-ALDH7A1 cohort. METHODS: Neurological outcome was assessed in 24 patients (age 1-26 years); classified as normal, complex minor neurological dysfunction (complex MND) or abnormal. Intelligence quotient (IQ) was derived from standardized IQ tests with five severity levels of intellectual disability (ID). MRI's and treatments were assessed. RESULTS: Ten patients (42%) showed unremarkable neurological examination, 11 (46%) complex MND, and 3 (12%) cerebral palsy (CP). Minor coordination problems were identified in 17 (71%), fine motor disability in 11 (46%), posture/muscle tone deviancies in 11 (46%) and abnormal reflexes in 8 (33%). Six patients (25%) had an IQ > 85, 7 (29%) borderline, 7 (29%) mild, 3 (13%) moderate, and 1 severe ID. Cerebral ventriculomegaly on MRI was progressive in 11. Three patients showed normal neurologic exam, IQ, and MRI. Eleven patients were treated with pyridoxine only and 13 by additional lysine reduction therapy (LRT). LRT started at age <3 years demonstrated beneficial effect on IQ results in 3 patients. DISCUSSION: Complex MND and CP occurred more frequently in PDE-ALDH7A1 (46% and 12%) than in general population (7% and 0.2%, Peters et al., 2011, Schaefer et al., 2008). Twenty-five percent had a normal IQ. Although LRT shows potential to improve outcomes, data are heterogeneous in small patient numbers. More research with longer follow-up via the International PDE Registry (www.pdeonline.org) is needed.

Cellulose microfibril deposition: coordinated activity at the plant plasma membrane.

Plant cell wall production is a membrane-bound process. Cell walls are composed of cellulose microfibrils, embedded inside a matrix of other polysaccharides and glycoproteins. The cell wall matrix is extruded into the existing cell wall by exocytosis. This same process also inserts the cellulose synthase complexes into the plasma membrane. These complexes, the nanomachines that produce the cellulose microfibrils, move inside the plasma membrane leaving the cellulose microfibrils in their wake. Cellulose microfibril angle is an important determinant of cell development and of tissue properties and as such relevant for the industrial use of plant material. Here, we provide an integrated view of the events taking place in the not more than 100 nm deep area in and around the plasma membrane, correlating recent results provided by the distinct field of plant cell biology. We discuss the coordinated activities of exocytosis, endocytosis, and movement of cellulose synthase complexes while producing cellulose microfibrils and the link of these processes to the cortical microtubules.

Sphere size distributions from finite thickness sections: a forward approach employing a genetic algorithm.

We formulate, implement and test a robust method of determining sphere size distributions from finite thickness planar sections. The method uses a forward approach in which populations of proposed distributions are tested against the input data and refined using a genetic algorithm. This method is then applied to a real-world data set concerning endo- and exocytotic vesicles in the apical region of tip growing pollen tubes of Arabidopsis thaliana.

Rates of exocytosis and endocytosis in Arabidopsis root hairs and pollen tubes.

Exocytosis and endocytosis are pivotal in many biological processes, but remain difficult to quantify. Here we combine a new algorithm for estimating vesicle size with a detailed morphological analysis of tip-growing cells, in which exocytosis is highly localized and therefore more readily quantified. Cell preservation was rendered as life-like as possible by rapid freezing. This allowed us to produce the first estimates of exocytosis rates in the root hairs and pollen tubes of the model plant Arabidopsis. To quantify exocytosis and endocytosis rates during cell growth, we measured the diameter of vesicles located in the tips of Arabidopsis root hairs and pollen tubes and the widths of cell walls and the cell lumen in longitudinal thin transmission electron microscopic sections. In addition, we measured growth velocities of Arabidopsis root hairs and pollen tubes, using video microscopy. The number of exocytotic vesicles required for cell wall expansion, and the amount of excess membrane inserted into the plasma membrane to be internalized, were estimated from the values that were obtained. The amount of excess membrane that is inserted into the plasma membrane during cell growth was estimated as 86.7% in root hairs and 79% in pollen tubes. This membrane has to be recycled by endocytosis. From counting of the total number of vesicles that is present in thin EM sections through the pollen tube tip, we estimated the average number of vesicles that is present in the tip of pollen tubes. By calculating the total amount of membrane and cell wall material that is required for continued cell growth, assuming that all vesicles are exocytotic, we estimated that pollen tubes continue to grow for 33 s when delivery of vesicles to the tip is inhibited. We arrested vesicle delivery to the tip by application of cytochalasin D. After cytochalasin D application, pollen tubes continued to grow for 30-40 s, which is in the same range as the estimated value of 33 s and shows that in this time frame, the availability of exocytotic vesicles is not a limiting factor.

Spectrin-like proteins in plant nuclei.

We analysed the presence and localization of spectrin-like proteins in nuclei of various plant tissues, using several anti-erythrocyte spectrin antibodies on isolated pea nuclei and nuclei in cells. Western blots of extracted purified pea nuclei show a cross-reactive pair of bands at 220-240 kDa, typical for human erythrocyte spectrin, and a prominent 60 kDa band. Immunolocalization by means of confocal laser scanning microscopy reveals spectrin-like proteins in distinct spots equally distributed in the nucleoplasm and over the nuclear periphery, independent of the origin of the anti-spectrin antibodies used. In some nuclei tracks of spectrin-like proteins are also observed. No signal is present in nucleoli. The amount and intensity of signal increases when nuclei were extracted, successively, with detergents, DNase I and RNase A, and high salt, indicating that the spectrin-like protein is associated with the nuclear matrix. The labelling is similar in nuclei of various plant tissues. These data are the first that show the presence and localization of spectrin-like epitopes in plant nuclei, where they may stabilize specific interchromatin domains.

Personality and susceptibility to positive and negative emotional states.

Gray's (1981) theory suggests that extraverts and neurotics are differentially sensitive to stimuli that generate positive and negative affect, respectively. From this theory it was hypothesized that efficacy of a standard positive-affect induction would be more strongly related to extraversion than to neuroticism scores, whereas efficacy of a standard negative-affect induction would be more strongly related to neuroticism scores. Positive and negative affect was manipulated in a controlled setting, and the effectiveness of the mood induction was assessed using standard mood adjective rating scales. Results are consistent with the hypothesis that neurotic Ss (compared with stable Ss) show heightened emotional reactivity to the negative-mood induction, whereas extraverts (compared with intraverts) show heightened emotional reactivity to the positive-mood induction. Results corroborate and extend previous findings.