Exploring Crystal Phase Switching in GaP Nanowires.

The growth of wurtzite/zincblende (WZ and ZB, respectively) superstructures opens new avenues for band structure engineering and holds the promise of digitally controlling the energy spectrum of quantum confined systems. Here, we study growth kinetics of pure and thus defect-free WZ/ZB homostructures in GaP nanowires with the aim to obtain monolayer control of the ZB and WZ segment lengths. We find that the Ga concentration and the supersaturation in the catalyst particle are the key parameters determining growth kinetics. These parameters can be tuned by the gallium partial pressure and the temperature. The formation of WZ and ZB can be understood with a model based on nucleation either at the triple phase line for the WZ phase or in the center of the solid-liquid interface for the ZB phase. Furthermore, the observed delay/offset time needed to induce WZ and ZB growth after growth of the other phase can be explained within this framework.

The effect of temperature and dot size on the spectral properties of colloidal InP/ZnS core-shell quantum dots.

Visual color changes between 300 and 510 K were observed in the photoluminescence (PL) of colloidal InP/ZnS core-shell nanocrystals. A subsequent study of PL spectra in the range 2-510 K and fitting the temperature dependent line shift and line width to theoretical models show that the dominant (dephasing) interaction is due to scattering by acoustic phonons of about 23 meV. Low temperature photoluminescence excitation measurements show that the excitonic band gap depends approximately inversely linearly on the quantum dot size d, which is distinctly weaker than the dependence predicted by current theories.

Targeted disruption of semaphorin 3C leads to persistent truncus arteriosus and aortic arch interruption.

Semaphorin 3C is a secreted member of the semaphorin gene family. To investigate its function in vivo, we have disrupted the semaphorin 3C locus in mice by targeted mutagenesis. semaphorin 3C mutant mice die within hours after birth from congenital cardiovascular defects consisting of interruption of the aortic arch and improper septation of the cardiac outflow tract. This phenotype is similar to that reported following ablation of the cardiac neural crest in chick embryos and resembles congenital heart defects seen in humans. Semaphorin 3C is expressed in the cardiac outflow tract as neural crest cells migrate into it. Their entry is disrupted in semaphorin 3C mutant mice. These data suggest that semaphorin 3C promotes crest cell migration into the proximal cardiac outflow tract.

PlexinA2 and semaphorin signaling during cardiac neural crest development.

Classic studies using avian model systems have demonstrated that cardiac neural crest cells are required for proper development of the cardiovascular system. Environmental influences that perturb neural crest development cause congenital heart defects in laboratory animals and in man. However, little progress has been made in determining molecular programs specifically regulating cardiac neural crest migration and function. Only recently have complex transgenic tools become available that confirm the presence of cardiac neural crest cells in the mammalian heart. These studies have relied upon the use of transgenic mouse lines and fate-mapping studies using Cre recombinase and neural crest-specific promoters. In this study, we use these techniques to demonstrate that PlexinA2 is expressed by migrating and postmigratory cardiac neural crest cells in the mouse. Plexins function as co-receptors for semaphorin signaling molecules and mediate axon pathfinding in the central nervous system. We demonstrate that PlexinA2-expressing cardiac neural crest cells are patterned abnormally in several mutant mouse lines with congenital heart disease including those lacking the secreted signaling molecule Semaphorin 3C. These data suggest a parallel between the function of semaphorin signaling in the central nervous system and in the patterning of cardiac neural crest in the periphery.

Difference between blocking and Néel temperatures in the exchange biased Fe3O4/CoO system.

The blocking temperature T(B) has been determined as a function of the antiferromagnetic layer thickness in the Fe3O4/CoO exchange biased system. For CoO layers thinner than 50 A, T(B) is reduced below the Néel temperature T(N) of bulk CoO (291 K), independent of crystallographic orientation or film substrate ( alpha-Al2O3, SrTiO3, and MgO). Neutron diffraction studies show that T(B) does not track the CoO ordering temperature and, hence, that this reduction in T(B) does not arise from finite-size scaling. Instead, the ordering temperature of the CoO layers is enhanced above the bulk T(N) for layer thicknesses approximately less than or equal to 100 A due to the proximity of magnetic Fe3O4 layers.

A high-resolution radiation hybrid map of the proximal portion of mouse chromosome 5.

Radiation hybrid (RH) mapping of the mouse genome provides a useful tool in the integration of existing genetic and physical maps, as well as in the ongoing effort to generate a dense map of expressed sequence tags. To facilitate functional analysis of mouse Chromosome 5, we have constructed a high-resolution RH map spanning 75 cM of the chromosome. During the course of these studies, we have developed RHBase, an RH data management program that provides data storage and an interface to several RH mapping programs and databases. We have typed 95 markers on the T31 RH panel and generated an integrated map, pooling data from several sources. The integrated RH map ranges from the most proximal marker, D5Mit331 (Chromosome Committee offset, 3 cM), to D5Mit326, 74.5 cM distal on our genetic map (Chromosome Committee offset, 80 cM), and consists of 138 markers, including 89 simple sequence length polymorphic markers, 11 sequence-tagged sites generated from BAC end sequence, and 38 gene loci, and represents average coverage of approximately one locus per 0.5 cM with some regions more densely mapped. In addition to the RH mapping of markers and genes previously localized on mouse Chromosome 5, this RH map places the alpha-4 GABA(A) receptor subunit gene (Gabra4) in the central portion of the chromosome, in the vicinity of the cluster of three other GABA(A) receptor subunit genes (Gabrg1-Gabra2-Gabrb1). Our mapping effort has also defined a new cluster of four genes in the semaphorin gene family (Sema3a, Sema3c, Sema3d, and Sema3e) and the Wolfram syndrome gene (Wfs1) in this region of the chromosome.

A dominant negative receptor for specific secreted semaphorins is generated by deleting an extracellular domain from neuropilin-1.

Neuropilins have recently been characterized as receptors for secreted semaphorins. Here, we report the generation of a dominant negative form of neuropilin-1 by the deletion of one of its extracellular domains. Expression of this variant in cultured primary sympathetic neurons blocks the paralysis of growth cone motility normally induced by SEMA-3A (collapsin-1, semaphorin III, semaphorin D) and SEMA-3C (collapsin-3, semaphorin E) but not that induced by SEMA-3F (semaphorin IV). A truncated form of neuropilin-1 that is missing its cytoplasmic domain fails to act as a dominant negative receptor component. These results suggest that neuropilin-1 is a necessary component of receptor complexes for some, but not all, secreted semaphorin family members. Overexpression of dominant negative neuropilins should provide a powerful new method of blocking the functions of secreted semaphorins.

Neuropilin-1 mediates collapsin-1/semaphorin III inhibition of endothelial cell motility: functional competition of collapsin-1 and vascular endothelial growth factor-165.

Neuropilin-1 (NRP1) is a receptor for two unrelated ligands with disparate activities, vascular endothelial growth factor-165 (VEGF165), an angiogenesis factor, and semaphorin/collapsins, mediators of neuronal guidance. To determine whether semaphorin/collapsins could interact with NRP1 in nonneuronal cells, the effects of recombinant collapsin-1 on endothelial cells (EC) were examined. Collapsin-1 inhibited the motility of porcine aortic EC (PAEC) expressing NRP1 alone; coexpressing KDR and NRP1 (PAEC/KDR/NRP1), but not parental PAEC; or PAEC expressing KDR alone. The motility of PAEC expressing NRP1 was inhibited by 65-75% and this inhibition was abrogated by anti-NRP1 antibody. In contrast, VEGF165 stimulated the motility of PAEC/KDR/NRP1. When VEGF165 and collapsin-1 were added simultaneously to PAEC/KDR/NRP1, dorsal root ganglia (DRG), and COS-7/NRP1 cells, they competed with each other in EC motility, DRG collapse, and NRP1-binding assays, respectively, suggesting that the two ligands have overlapping NRP1 binding sites. Collapsin-1 rapidly disrupted the formation of lamellipodia and induced depolymerization of F-actin in an NRP1-dependent manner. In an in vitro angiogenesis assay, collapsin-1 inhibited the capillary sprouting of EC from rat aortic ring segments. These results suggest that collapsin-1 can inhibit EC motility as well as axon motility, that these inhibitory effects on motility are mediated by NRP1, and that VEGF165 and collapsin-1 compete for NRP1-binding sites.

A 70 amino acid region within the semaphorin domain activates specific cellular response of semaphorin family members.

The semaphorin family contains secreted and transmembrane signaling proteins that function in the nervous, immune, and cardiovascular systems. Chick collapsin-1 is a repellent for specific growth cones. Two other secreted members of the semaphorin family, collapsin-2 and -3, are structurally similar to collapsin-1 but have different biological activities. Semaphorins contain a 500 amino acid family signature semaphorin domain. We show in this study that (1) the semaphorin domain of collapsin-1 is both necessary and sufficient for biological activity, (2) the semaphorin domain contains a 70 amino acid region that specifies the biological activity of the three family members, and (3) the positively charged carboxy terminus potentiates activity without affecting specificity. We propose that semaphorins interact with their receptors through two independent binding sites: one that mediates the biological response and one that potentiates it.

Secreted chick semaphorins bind recombinant neuropilin with similar affinities but bind different subsets of neurons in situ.

Collapsin-1, a member of the semaphorin family, activates receptors on specific growth cones, thereby inhibiting their motility. Neuropilin, a previously cloned transmembrane protein, has recently been identified as a candidate receptor for collapsin-1. We have completed the cloning of chick collapsin-3 and -5 and show that collapsin-1, -2, -3, and -5 bind to overlapping but distinct axon tracts. We infer that in situ, there are distinct receptors with different affinities for collapsin-1, -2, -3, and -5. In contrast, these four collapsins all bind recombinant neuropilin with similar affinities. Strong binding to neuropilin is mediated by the carboxy third of the collapsins, while the semaphorin domain confers their unique binding patterns in situ. We propose that neuropilin is a common component of a semaphorin receptor complex, and that additional differentially expressed receptor components interact with the semaphorin domains to confer binding specificity.

Monoclonal antibody PHF-1 recognizes tau protein phosphorylated at serine residues 396 and 404.

The microtubule-associated protein tau is hyperphosphorylated in the paired helical filaments (PHFs) of Alzheimer's disease. Immunological and direct chemical studies have identified Ser396 and Ser404 as two of the phosphorylated sites. Previously, we have demonstrated, using synthetic tau peptides containing phosphorylated Ser396, that this site is recognized by the monoclonal antibody PHF-1. The present study extends this observation by showing that PHF-1 recognizes tau peptides containing either individually phosphorylated Ser396 or Ser404, but that there is a > 10-fold increase in the sensitivity of detection of tau peptides by PHF-1 when both serines are phosphorylated. The recognition of singly or doubly phosphorylated Ser396 and Ser404 in tau by PHF-1 can also be demonstrated in Chinese hamster ovary cells transfected with full-length wild-type tau constructs or mutant constructs with Ala substituted for Ser396 or Ser404. We conclude that the PHF-1 epitope contains both phosphorylated Ser396 and Ser404.

Optic neuropathy and amiodarone therapy.

Optic neuropathy has been diagnosed in several amiodarone-treated patients, including the 13 patients described in this report. The clinical severity of this drug-related optic neuropathy is milder than that characteristically described in anterior ischemic optic neuropathy. The incidence of occurrence was significantly higher than that found in an age-matched general population sample. Whether this result was due solely to amiodarone therapy, to the underlying poor health of these patients, or to a combination of these two factors is uncertain. The findings in this study prompt us to recommend that all patients who receive amiodarone undergo complete ophthalmologic examinations, including careful evaluation of the ocular fundus regularly during such therapy. Appearance of optic neuropathy is probably a relative indication for discontinuing the use of the drug, in the hopes of avoiding bilateral involvement or perhaps recovering vision. The risks of complications of amiodarone treatment must be weighed against the benefit of therapy in patients whose lives are threatened by cardiac arrhythmias. On the basis of this study, the benefits of treatment seem to outweigh the small risk of optic neuropathy. No randomized study has been undertaken to determine the true incidence of complications associated with this medication and at this time could not be justified.

Progression of pseudovitelliform macular dystrophy.

Pseudovitelliform macular dystrophy is a dominantly inherited macular disorder. It is characterized by the presence of horizontally oval yellowish deposits within the maculas that are approximately one-third disc diameter in size. As classically described, progression of the lesions over a follow-up period of as long as six years has not been described and the prognosis for retention of good visual function is excellent. We report the ophthalmoscopic appearance of six eyes of three patients from a very subtle alteration of macular pigmentation to severe disruption of macular architecture, and demonstrate in one of our patients drastic deterioration in both ophthalmoscopic appearance and visual function over a three-year period of follow-up. The prognosis for retention of good vision in this disorder must include the possibility of the eventual development of severe visual impairment.

Retinal arterial occlusive disease in systemic lupus erythematosus.

Four patients with systemic lupus erythematosus (SLE) developed an unusual form of occlusive retinal arterial disease. The most prominent clinical features of this disorder were deposition of yellow-white material in retinal arterial walls and evidence of multifocal retinal arterial occlusion. Fluorescein angiographic findings included nonperfusion of the obstructed arteries and the retinal capillary beds fed by them, and fluorescein leakage at the sites of involvement of the retinal arteries. This ocular complication of SLE is presumably a manifestation of the widespread systemic vascular problems seen in this disorder. It may be more common in patients with lupus involving the CNS.