Predictability of food supply, but not ration, increases exploratory behaviour in zebrafish Danio rerio.

Individual zebrafish Danio rerio were assayed for exploratory tendency in a serial open field test before and after being maintained on one of four diet treatments that differed in ration and in predictability of food delivery. Danio rerio became more exploratory after being maintained on a diet with a predictable delivery schedule. There was no effect of ration. Thus, exploratory behaviour is inducible by environmental influences independent of genetic predisposition or social interactions. These results have implications for management of correlated behavioural syndromes of exploratory and boldness of animals reared in captivity for later release into wild populations.

Outcomes of splenectomy in patients with common variable immunodeficiency (CVID): a survey of 45 patients.

Splenectomy has been used in patients with common variable immunodeficiency disorders (CVID), mainly in the context of refractory autoimmune cytopenia and suspected lymphoma, but there are understandable concerns about the potential of compounding an existing immunodeficiency. With increasing use of rituximab as an alternative treatment for refractory autoimmune cytopenia, the role of splenectomy in CVID needs to be re-examined. This retrospective study provides the largest cohesive data set to date describing the outcome of splenectomy in 45 CVID patients in the past 40 years. Splenectomy proved to be an effective long-term treatment in 75% of CVID patients with autoimmune cytopenia, even in some cases when rituximab had failed. Splenectomy does not worsen mortality in CVID and adequate immunoglobulin replacement therapy appears to play a protective role in overwhelming post-splenectomy infections. Future trials comparing the effectiveness and safety of rituximab and splenectomy are needed to provide clearer guidance on the second-line management of autoimmune cytopenia in CVID.

Skeletal overgrowth and deafness in mice lacking fibroblast growth factor receptor 3.

Fibroblast growth factor receptor 3 (Fgfr3) is a tyrosine kinase receptor expressed in developing bone, cochlea, brain and spinal cord. Achondroplasia, the most common genetic form of dwarfism, is caused by mutations in FGFR3. Here we show that mice homozygous for a targeted disruption of Fgfr3 exhibit skeletal and inner ear defects. Skeletal defects include kyphosis, scoliosis, crooked tails and curvature and overgrowth of long bones and vertebrae. Contrasts between the skeletal phenotype and achondroplasia suggest that activation of FGFR3 causes achondroplasia. Inner ear defects include failure of pillar cell differentiation and tunnel of Corti formation and result in profound deafness. Our results demonstrate that Fgfr3 is essential for normal endochondral ossification and inner ear development.

Defects in neural stem cell proliferation and olfaction in Chd7 deficient mice indicate a mechanism for hyposmia in human CHARGE syndrome.

Mutations in CHD7, a chromodomain gene, are present in a majority of individuals with CHARGE syndrome, a multiple anomaly disorder characterized by ocular Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital hypoplasia and Ear anomalies. The clinical features of CHARGE syndrome are highly variable and incompletely penetrant. Olfactory dysfunction is a common feature in CHARGE syndrome and has been potentially linked to primary olfactory bulb defects, but no data confirming this mechanistic link have been reported. On the basis of these observations, we hypothesized that loss of Chd7 disrupts mammalian olfactory tissue development and function. We found severe defects in olfaction in individuals with CHD7 mutations and CHARGE, and loss of odor evoked electro-olfactogram responses in Chd7 deficient mice, suggesting reduced olfaction is due to a dysfunctional olfactory epithelium. Chd7 expression was high in basal olfactory epithelial neural stem cells and down-regulated in mature olfactory sensory neurons. We observed smaller olfactory bulbs, reduced olfactory sensory neurons, and disorganized epithelial ultrastructure in Chd7 mutant mice, despite apparently normal functional cilia and sustentacular cells. Significant reductions in the proliferation of neural stem cells and regeneration of olfactory sensory neurons in the mature Chd7(Gt/+) olfactory epithelium indicate critical roles for Chd7 in regulating neurogenesis. These studies provide evidence that mammalian olfactory dysfunction due to Chd7 haploinsufficiency is linked to primary defects in olfactory neural stem cell proliferation and may influence olfactory bulb development.

Drosophila APC2 and Armadillo participate in tethering mitotic spindles to cortical actin.

Proper positioning of mitotic spindles ensures equal allocation of chromosomes to daughter cells. This often involves interactions between spindle and astral microtubules and cortical actin. In yeast and Caenorhabditis elegans, some of the protein machinery that connects spindles and cortex has been identified but, in most animal cells, this process remains mysterious. Here, we report that the tumour suppressor homologue APC2 and its binding partner Armadillo both play roles in spindle anchoring during the syncytial mitoses of early Drosophila embryos. Armadillo, alpha-catenin and APC2 all localize to sites of cortical spindle attachment. APC2-Armadillo complexes often localize with interphase microtubules. Zeste-white 3 kinase, which can phosphorylate Armadillo and APC, is also crucial for spindle positioning and regulates the localization of APC2-Armadillo complexes. Together, these data suggest that APC2, Armadillo and alpha-catenin provide an important link between spindles and cortical actin, and that this link is regulated by Zeste-white 3 kinase.

Pathotypes, Distribution, and Metalaxyl Sensitivity of Phytophthora sojae from North Dakota.

Phytophthora root rot, caused by Phytophthora sojae, is the most important disease of soybean (Glycine max) in North Dakota. Because of the expansion of soybean hectares and appearance of disease on cultivars with resistance genes, we investigated the pathotypes, distribution, and metalaxyl sensitivity of P. sojae in North Dakota. Soil from 347 soybean fields in 20 counties in eastern North Dakota was collected between 2002 and 2004, and P. sojae was baited from the soil with the susceptible cultivar McCall. The virulence phenotype of each isolate was determined on eight differentials, and all isolates were tested for sensitivity to metalaxyl incorporated into V8 agar. The pathogen was recovered from 80 fields located in five counties. Sixteen pathotypes, which included 14 known races and two previously reported pathotypes that had not been assigned a race, were identified out of 157 isolates. A single pathotype was recovered from 61 fields, 2 pathotypes from 14 fields, 3 pathotypes from 4 fields, and 4 pathotypes from 1 field. Pathotypes with virulence phenotypes 1a,1c,7 (race 4; 39%) and 1a,7 (race 3; 28%) were the most common, representing 67% of the total isolates. One or both of these pathotypes was found in 79% of the fields where P. sojae was recovered. Seven of the 157 isolates showed limited growth on metalaxyl after 14 days of incubation. In the past 10 years, the number of pathotypes of P. sojae in North Dakota has increased from 4 to 16, and pathotypes have developed that can attack the three most common resistance genes found in soybean cultivars for the region.

Wnt signaling: the naked truth?

Frizzled receptors can activate two alternative signal transduction pathways: the canonical Wnt pathway or the planar cell polarity pathway. Recent studies of the Naked cuticle protein suggest a mechanism for the inactivation of the canonical pathway and concomitant activation of the planar cell polarity pathway.

Contactin associates with Na+ channels and increases their functional expression.

Contactin (also known as F3, F11) is a surface glycoprotein that has significant homology with the beta2 subunit of voltage-gated Na(+) channels. Contactin and Na(+) channels can be reciprocally coimmunoprecipitated from brain homogenates, indicating association within a complex. Cells cotransfected with Na(+) channel Na(v)1.2alpha and beta1 subunits and contactin have threefold to fourfold higher peak Na(+) currents than cells with Na(v)1.2alpha alone, Na(v)1.2/beta1, Na(v)1.2/contactin, or Na(v)1.2/beta1/beta2. These cells also have a correspondingly higher saxitoxin binding, suggesting an increased Na(+) channel surface membrane density. Coimmunoprecipitation of different subunits from cell lines shows that contactin interacts specifically with the beta1 subunit. In the PNS, immunocytochemical studies show a transient colocalization of contactin and Na(+) channels at new nodes of Ranvier forming during remyelination. In the CNS, there is a particularly high level of colocalization of Na(+) channels and contactin at nodes both during development and in the adult. Contactin may thus significantly influence the functional expression and distribution of Na(+) channels in neurons.

A novel epilepsy mutation in the sodium channel SCN1A identifies a cytoplasmic domain for beta subunit interaction.

A mutation in the sodium channel SCN1A was identified in a small Italian family with dominantly inherited generalized epilepsy with febrile seizures plus (GEFS+). The mutation, D1866Y, alters an evolutionarily conserved aspartate residue in the C-terminal cytoplasmic domain of the sodium channel alpha subunit. The mutation decreased modulation of the alpha subunit by beta1, which normally causes a negative shift in the voltage dependence of inactivation in oocytes. There was less of a shift with the mutant channel, resulting in a 10 mV difference between the wild-type and mutant channels in the presence of beta1. This shift increased the magnitude of the window current, which resulted in more persistent current during a voltage ramp. Computational analysis suggests that neurons expressing the mutant channels will fire an action potential with a shorter onset delay in response to a threshold current injection, and that they will fire multiple action potentials with a shorter interspike interval at a higher input stimulus. These results suggest a causal relationship between a positive shift in the voltage dependence of sodium channel inactivation and spontaneous seizure activity. Direct interaction between the cytoplasmic C-terminal domain of the wild-type alpha subunit with the beta1 or beta3 subunit was first demonstrated by yeast two-hybrid analysis. The SCN1A peptide K1846-R1886 is sufficient for beta subunit interaction. Coimmunoprecipitation from transfected mammalian cells confirmed the interaction between the C-terminal domains of the alpha and beta1 subunits. The D1866Y mutation weakens this interaction, demonstrating a novel molecular mechanism leading to seizure susceptibility.

A screen for mutations that suppress the phenotype of Drosophila armadillo, the beta-catenin homolog.

During development signaling pathways coordinate cell fates and regulate the choice between cell survival or programmed cell death. The well-conserved Wingless/Wnt pathway is required for many developmental decisions in all animals. One transducer of the Wingless/Wnt signal is Armadillo/beta-catenin. Drosophila Armadillo not only transduces Wingless signal, but also acts in cell-cell adhesion via its role in the epithelial adherens junction. While many components of both the Wingless/Wnt signaling pathway and adherens junctions are known, both processes are complex, suggesting that unknown components influence signaling and junctions. We carried out a genetic modifier screen to identify some of these components by screening for mutations that can suppress the armadillo mutant phenotype. We identified 12 regions of the genome that have this property. From these regions and from additional candidate genes tested we identified four genes that suppress arm: dTCF, puckered, head involution defective (hid), and Dpresenilin. We further investigated the interaction with hid, a known regulator of programmed cell death. Our data suggest that Wg signaling modulates Hid activity and that Hid regulates programmed cell death in a dose-sensitive fashion.

Subcellular and developmental expression of alternatively spliced forms of fibroblast growth factor 14.

Fibroblast growth factors (FGFs) 11-14 comprise a subfamily of FGFs with poorly defined biological function. Here we characterize two isoforms of FGF14 (FGF14-1a and FGF14-1b) that result from the alternative usage of two different first exons. We demonstrate that these isoforms have differential subcellular localization and that they are differentially expressed in various adult tissues. Using in situ hybridization we show that Fgf14 is widely expressed in brain, spinal cord, major arteries and thymus between 12.5 and 14.5 days of mouse embryonic development. We also show that during cerebellar development, Fgf14 is first observed at postnatal day 1 in post mitotic granule cells, and later in development, in migrating and post migratory granule cells. The developmental expression pattern of Fgf14 in the cerebellum is complementary to that of Math1, a marker for proliferating granule cells in the external germinal layer.

Water Environment Research Foundation (WERF) anaerobic digestion and related processes, odour and health effects study.

Biosolids odour emissions can affect the ability of wastewater utilities to implement beneficial biosolids processing and reuse programs. Communities often become more sensitised and vocal about biosolids issues, once they experience odours emanating from a nearby site. Odour impacts from biosolids, including potential human health effects, have been targeted recently by many national and local newspapers, citizens' groups, and regulatory agencies, who have raised significant concerns, ranging from viable disposal methods/sites to outright bans. Many national and local regulatory agencies in the United States are considering biosolids disposal bans in their communities because of misinformation, poor science, and citizen pressure, but primarily because of odour impact concerns. The wastewater industry has a relatively poor understanding of the operations and treatment parameters that influence biosolids odour emissions. Thus, wastewater treatment plants are often unable to control the odour quality of the biosolids that are delivered into communities. A research study to demonstrate the influence of anaerobic digestion, mechanical dewatering, and storage design and operating parameters on the odour quality of the final product was performed and is the subject of this paper. Established and new sampling and analytical methods were used to measure biosolids odour emissions from 11 test sites in North America. By determining the impacts of these control variables on biosolids odour quality, design and operations of anaerobic digestion systems might be enhanced. This paper also summarises a corollary study performed as part of the WERF research study that addresses the health effects of biosolids odours.

Diaphragmatic pacing. An option for patients with quadriplegic respiratory paralysis.

Recent advances in design, increased reliability, and computerized pacing provide an exciting alternative to mechanical ventilation for the quadriplegic patient. Research into the development of totally implantable, demand-type respiratory pacemakers is ongoing. Careful patient selection, meticulous surgical technique, adequate training in the use of the device, and conscientious follow-up contribute to a successful outcome--increased mobility and independence for the ventilator-dependent quadriplegic patient.

Arteriovenous fistula. Vascular access for long-term hemodialysis.

Long-term hemodialysis remains the most important support for patients with ESRD, and reliable vascular access is an essential component of this management plan. Recent refinements in AV fistula surgical techniques have produced this dependable, well-tolerated, long-term access route for hemodialysis.

Transsphenoidal adenomectomy.

The pituitary gland is a complex organ controlling many of the body's hormonal and metabolic functions. The gland's complexity and location in the brain have a serious impact on the diagnosis and treatment of pituitary pathology. Several surgical approaches are available to treat pituitary tumors; however, the transsphenoidal approach allows the surgeon to remove the tumor with minimal damage to surrounding intracranial structures. Perioperative nurses should be knowledgeable about pituitary pathology (ie, mass effect, hormonal involvement), patient treatment options, surgical approaches, and possible postoperative complications to provide quality nursing care.

Management of alcoholic cirrhosis of the liver.

Patients with liver disease require skilled, complex management of the inevitable complications associated with hepatic dysfunction. Portal hypertension, a major consequence of cirrhosis of the liver, causes ascites and esophageal variceal hemorrhages. Many clinical and surgical treatment options are available to manage these complications; however, they often produce only temporary symptom control and may beget further morbidity. This article focuses on the etiology, complications, and treatment of alcoholic cirrhosis. Perioperative nursing care of patients with alcoholic cirrhosis is based on an understanding of normal hepatic functions and the systemic effects of cirrhosis.

Surgical treatment of dacryocystitis.

Dacryocystitis is a common infection of the lacrimal sac. In adults, dacryocystitis results from an obstruction (ie, dacryostenosis) of the nasolacrimal duct. Dacryocystitis can be either an acute or chronic infection, and both forms usually are unilateral in nature. The hallmark symptom of both forms of dacryocystitis is epiphora (ie, excessive tearing). An obstruction of the lacrimal duct also can cause dacryocystitis. This article discusses the surgical treatment of dacryocystitis and provides a case study that illustrates perioperative nursing care of a patient who required surgical treatment of this lacrimal duct disorder.

Intraoperative positioning of surgical patients.

All perioperative team members are responsible for the safe positioning of surgical patients. Circulating nurses coordinate the positioning of patients during intraoperative periods of care. Skilled perioperative nursing interventions afford patients safe and comfortable positioning during surgery, ensure optimal exposures of surgical sites, and prevent postoperative complications (e.g., pressure injuries, neuropathies, cardiovascular and respiratory compromises). Perioperative nurses should have a working knowledge of anatomy and physiology, patient risk factors, injury mechanisms, potential complications, and positioning devices before placing patients in required perioperative positions.

Complications associated with excision of a submandibular salivary gland tumor.

Recognition and timely correction of serious postoperative complications is essential for an optimal patient outcome. Rapid assessment and prompt treatment prevent irreversible patient complications. In Mr C's case, he has successfully returned to his full level of preoperative activities. His endocrinologist continues to monitor him on a regular basis for the nonpalpable masses found in his thyroid gland. Mr C considers his symptoms of Frey's syndrome only a minor annoyance.

Surgical treatment for intranasal squamous cell carcinoma.

Surgical treatment for aggressive intranasal squamous cell carcinoma (SCC) requires a multidisciplinary team approach to ensure optimal patient outcomes. Surgical procedures for the removal of intranasal malignancies may include rhinectomy, palatectomy, and maxillectomy. These procedures leave patients with significant facial defects that are corrected with staged surgical reconstructions or applications of facial prostheses. This article describes the etiology of intranasal SCC, discusses treatment options, and presents a case study that chronicles the events from diagnosis through rehabilitation of a patient undergoing rhinectomy, partial bilateral maxillectomy, and partial palatectomy.