Euhaplorchis californiensis Cercariae Exhibit Positive Phototaxis and Negative Geotaxis.

Parasites often use external cues to identify and move toward environments where they are likely to encounter suitable hosts. The trematode parasite Euhaplorchis californiensis produces cercariae that emerge from California horn snails ( Cerithideopsis californica [= Cerithidea californica]) to infect California killifish ( Fundulus parvipinnis) as second intermediate hosts. Based upon work on a congeneric Euhaplorchis species from Florida, and based on the ecology of its killifish host, we hypothesized that E. californiensis cercariae in southern California estuaries are positively phototactic and negatively geotactic, using both sunlight and gravity to guide their movement to the upper water column. To distinguish positive phototaxis from negative geotaxis, we first quantified E. californiensis movement in response to light along a horizontal plane and determined they were positively phototactic. In a second experiment, we quantified E. californiensis movement along a vertical plane in response to an overhead light, a light from below, or no light. We found that E. californiensis exhibit negative geotaxis in the absence of light, but will swim in the direction of gravity to move toward a light source from below. Thus, E. californiensis are both positively phototactic and negatively geotactic, but cercariae prioritize phototactic cues. These results suggest that E. californiensis cercariae aggregate in the open water, indicating that the pelagic zone represents an area of high infection risk for California killifish hosts.

Adolescent bullying, cannabis use and emerging psychotic experiences: a longitudinal general population study.

BACKGROUND: Using longitudinal and prospective measures of psychotic experiences during adolescence, we assessed the risk of developing psychosis in three groups showing low, increasing and elevated psychotic experiences associated with bullying by peers and cannabis use in a UK sample of adolescents. Method Data were collected by self-report from 1098 adolescents (mean age 13.6 years; 60.9% boys) at five separate time points, equally separated by 6 months, across a 24-month period. General growth mixture modelling identified three distinct trajectories of adolescents reporting psychotic experiences: elevated, increasing and low. RESULTS: Controlling for cannabis use, bullying by peers significantly predicted change in psychotic experiences between Time 2 and Time 5 in adolescents belonging to the increasing group. No effect was found for the elevated or low groups. Controlling for bullying, an earlier age of cannabis use and cannabis use more than twice significantly predicted change in psychotic experiences in adolescents belonging to the increasing group. Cannabis use at any age was significantly associated with subsequent change in psychotic experiences in the low group. Reverse causal associations were examined and there was no evidence for psychotic experiences at Time 1 predicting a subsequent change in cannabis use between Times 2 and 5 in any trajectory group. CONCLUSIONS: Bullying by peers and cannabis use are associated with adolescents' reports of increasing psychotic experiences over time. Further research into the longitudinal development of psychosis in adolescence and the associated risk factors would allow for early intervention programmes to be targeted more precisely.

Acute onset of infantile spinal muscular atrophy.

Two patients with acute generalized weakness and areflexia are presented. The electrophysiologic studies in both revealed evidence of decreased conduction velocity and mixed axonal and demyelinating neuropathy, suggestive of the diagnosis of Guillain-Barré syndrome. The young ages of the patients and their failure to respond to immunoglobulin therapy were the major clues to the final diagnosis of spinal muscular atrophy type I. Blood for DNA study revealed homozygous deletion mutation in exons 7 and 8 of the survival motor neuron gene. This diagnosis should be considered in every child under 1 year of age who presents with acute weakness because Guillain-Barré syndrome in this age group is rare.

Elevating the level of Cdc34/Ubc3 ubiquitin-conjugating enzyme in mitosis inhibits association of CENP-E with kinetochores and blocks the metaphase alignment of chromosomes.

Cdc34/Ubc3 is a ubiquitin-conjugating enzyme that functions in targeting proteins for proteasome-mediated degradation at the G1 to S cell cycle transition. Elevation of Cdc34 protein levels by microinjection of bacterially expressed Cdc34 into mammalian cells at prophase inhibited chromosome congression to the metaphase plate with many chromosomes remaining near the spindle poles. Chromosome condensation and nuclear envelope breakdown occurred normally, and chromosomes showed oscillatory movements along mitotic spindle microtubules. Most injected cells arrested in a prometaphase-like state. Kinetochores, even those of chromosomes that failed to congress, possessed the normal trilaminar plate ultrastructure. The elevation of Cdc34 protein levels in early mitosis selectively blocked centromere protein E (CENP-E), a mitotic kinesin, from associating with kinetochores. Other proteins, including two CENP-E-associated proteins, BubR1 and phospho-p42/p44 mitogen-activated protein kinase, and mitotic centromere-associated kinesin, cytoplasmic dynein, Cdc20, and Mad2, all exhibited normal localization to kinetochores. Proteasome inhibitors did not affect the prometaphase arrest induced by Cdc34 injection. These studies suggest that CENP-E targeting to kinetochores is regulated by ubiquitylation not involving proteasome-mediated degradation.

Acute necrotizing encephalopathy presenting as a basal ganglia syndrome.

Acute necrotizing encephalopathy is a relatively new disease. The characteristic clinical findings are of febrile illness followed by rapid deterioration in mental status and seizures. The hallmark of the disease is multifocal bilateral symmetric lesions affecting the thalamus, hypothalamus, brainstem tegmentum, cerebral white matter, and cerebellum. The etiology is unknown, but immune-mediated mechanism was suggested. We present a 12-year-old previously healthy girl who developed increased sleepiness progressing to stupor and coma. Magnetic resonance imaging (MRI) of the brain showed the characteristic findings previously described in acute necrotizing encephalopathy. Her mental status improved dramatically with steroid treatment, and the MRI findings resolved completely within 6 months. Following the acute illness, she developed a complex neuropsychiatric disorder consistent with basal ganglia syndrome.

Cell cycle-regulated proteolysis of mitotic target proteins.

The ubiquitin-dependent proteolysis of mitotic cyclin B, which is catalyzed by the anaphase-promoting complex/cyclosome (APC/C) and ubiquitin-conjugating enzyme H10 (UbcH10), begins around the time of the metaphase-anaphase transition and continues through G1 phase of the next cell cycle. We have used cell-free systems from mammalian somatic cells collected at different cell cycle stages (G0, G1, S, G2, and M) to investigate the regulated degradation of four targets of the mitotic destruction machinery: cyclins A and B, geminin H (an inhibitor of S phase identified in Xenopus), and Cut2p (an inhibitor of anaphase onset identified in fission yeast). All four are degraded by G1 extracts but not by extracts of S phase cells. Maintenance of destruction during G1 requires the activity of a PP2A-like phosphatase. Destruction of each target is dependent on the presence of an N-terminal destruction box motif, is accelerated by additional wild-type UbcH10 and is blocked by dominant negative UbcH10. Destruction of each is terminated by a dominant activity that appears in nuclei near the start of S phase. Previous work indicates that the APC/C-dependent destruction of anaphase inhibitors is activated after chromosome alignment at the metaphase plate. In support of this, we show that addition of dominant negative UbcH10 to G1 extracts blocks destruction of the yeast anaphase inhibitor Cut2p in vitro, and injection of dominant negative UbcH10 blocks anaphase onset in vivo. Finally, we report that injection of dominant negative Ubc3/Cdc34, whose role in G1-S control is well established and has been implicated in kinetochore function during mitosis in yeast, dramatically interferes with congression of chromosomes to the metaphase plate. These results demonstrate that the regulated ubiquitination and destruction of critical mitotic proteins is highly conserved from yeast to humans.

Protein dynamics at the kinetochore: cell cycle regulation of the metaphase to anaphase transition.

The spindle checkpoint blocks the initiation of anaphase in mitosis and meiosis if chromosomes are not aligned at the metaphase plate. The checkpoint functions by preventing a ubiquitin ligase called the anaphase-promoting complex/cyclosome (APC/C) from ubiquitinylating proteins whose destruction is required for anaphase onset. The spindle checkpoint signal originates at the kinetochores of unaligned chromosomes and is broadcast to the rest of the cell. Although the spindle checkpoint is not understood in detail, several components of the checkpoint-signaling pathway have been identified. Many of these components associate transiently with the kinetochores of unaligned chromosomes. We propose a model in which kinetochores that lack stable attachments to the spindle microtubules serve as catalytic staging areas for the assembly of inhibitor complexes. These inhibitor complexes then leave the kinetochores and block activity of the APC/C throughout the cell. We suggest that microtubule occupancy at kinetochores or physical tension induced by microtubule capture turns off the capability of the kinetochore to produce the APC/C inhibitor. Subsequently, the inhibitor concentration in the cell wanes and anaphase initiates.

Congenital aorto-caval fistula in the newborn: a case report.

The authors report a rare case of congenital fistula between the distal aspect of the descending aorta and the inferior vena cava. The clinical features of this aortocaval fistula is being described as well as the preoperative diagnostic workup, the intraoperative findings, and the complicated postoperative course and treatment.