Liquid crystal mediated interactions between nanoparticles in a nematic phase.

A continuum theory is used to study the interactions between nanoparticles suspended in nematic liquid crystals. The free energy functional that describes the system is minimized using an Euler-Lagrange approach and an unsymmetric radial basis function method. It is shown that nanoparticle liquid-crystal mediated interactions can be controlled over a large range of magnitudes through changes of the anchoring energy and the particle diameter. The results presented in this work serve to reconcile past discrepancies between theoretical predictions and experimental observations, and suggest intriguing possibilities for directed nanoparticle self-assembly in liquid crystalline media.

Autism-linked gene FoxP1 selectively regulates the cultural transmission of learned vocalizations.

Autism spectrum disorders (ASDs) are characterized by impaired learning of social skills and language. Memories of how parents and other social models behave are used to guide behavioral learning. How ASD-linked genes affect the intertwined aspects of observational learning and behavioral imitation is not known. Here, we examine how disrupted expression of the ASD gene FOXP1, which causes severe impairments in speech and language learning, affects the cultural transmission of birdsong between adult and juvenile zebra finches. FoxP1 is widely expressed in striatal-projecting forebrain mirror neurons. Knockdown of FoxP1 in this circuit prevents juvenile birds from forming memories of an adult song model but does not interrupt learning how to vocally imitate a previously memorized song. This selective learning deficit is associated with potent disruptions to experience-dependent structural and synaptic plasticity in mirror neurons. Thus, FoxP1 regulates the ability to form memories essential to the cultural transmission of behavior.

Projections of the oval nucleus of the hyperstriatum ventrale in the budgerigar: relationships with the auditory system.

The afferent and efferent projections of a vocal control nucleus, the oval nucleus of the hyperstriatum ventrale (HVo), were mapped out in a parrot, the budgerigar (Melopsittacus undulatus) to determine the relationships of this nucleus to the auditory system. In budgerigars, HVo is connected to both the anterior forebrain pathway as well as to nuclei forming the descending projection system to the brainstem (Durand et al. [1997] J. Comp. Neurol. 377:179-206). Previous studies (Brauth et al. [1997] Proc. N. Y. Acad. Sci. 807:368-385; Durand and Brauth [1998] Neurosci Abstr 24:78.9) indicate that HVo lesions disrupt vocal performance and that HVo neurons show long latency electrophysiologic auditory responses. HVo has also been shown to receive input from neurons in the immediately adjacent HV (Durand et al. [1997] J. Comp. Neurol. 377:179-206). Thus, the focus of the present study was to elucidate relationships between HVo, its immediately adjacent surround and telencephalic auditory nuclei. The results show that, although the lateral and medial portions of HVo are interconnected with one another, inputs to these areas and their surrounds are distinctively different. The most substantial auditory system inputs are derived from the frontal lateral neostriatum (NFl) and supracentral nucleus of the lateral neostriatum (NLs); these project primarily to the lateral HVo and lateral HVo surround. The medial HVo and surround receive only sparse or modest input from auditory nuclei, including the caudomedial neostriatum (NCM), neostriatum intermedium pars lateralis (NIL), Fields L1 and L3, and the neostriatum intermedium pars ventrolateralis (NIVL). Other sources of input to the HVo surround include the hyperstriatum accessorium (HA), the supralaminar area of the frontal neostriatum (NAs), the ventral anterior archistriatum (AAv), the medial archistriatum (Am) and the medial HV. Neurons in the HV immediately medial to HVo project to a shell region around the entire nucleus. Both the ventral paleostriatum (VP) and ventral part of the central nucleus of the lateral neostriatum (NLc) project to HVo but not to the surround. Previously described projections (Durand et al., 1997) from HVo to the NAom, NLc, and the magnicellular nucleus of the lobus parolfactorius (LPOm) were confirmed.

Distribution of tyrosine hydroxylase-containing neurons and fibers in the brain of the budgerigar (Melopsittacus undulatus): general patterns and labeling in vocal control nuclei.

The distribution of tyrosine hydroxylase (TH) was mapped out in cells and fibers of the budgerigar (Melopsittacus undulatus) brain. Special attention was given to vocal control and auditory nuclei because budgerigars are a psittacine species in which both males and females are capable of lifelong vocal learning (Farabaugh et al. [1994] J. Comp. Psychol 108:81-92). The results show that TH staining in the central nucleus of the anterior archistriatum (AAc) resembled that of surrounding archistriatal fields, except for portions of the ventral archistriatum, which exhibited substantially more TH+ fibers. Fewer fibers and fiber baskets are present in the central nucleus of the lateral neostriatum (NLc) than in surrounding fields. Both the oval nuclei of the ventral hyperstriatum (HVo) and anterior neostriatum (NAo) exhibit less fiber staining than surrounding fields whereas fiber staining in the medial NAo (NAom) and magnicellular nucleus of the parolfactory lobe (LPOm) resemble that of surrounding fields. Staining in primary telencephalic auditory nuclei was extremely low. The only sex difference observed was slightly increased TH staining in LPOm of females compared with surrounding fields on some tissue sections. These findings are in contrast to previous findings in zebra finch (Poephila guttata), a close ended vocal learning songbird in which TH staining in vocal nuclei increases during development and remains greater than surrounding fields throughout adulthood. The present results therefore support the view that catecholamines act to inhibit vocal plasticity in adult vocal learning species. Several unique features of TH-immunoreactive (ir) cell groups were observed in the brainstem including sparsely scattered TH-ir somata immediately adjacent to the third ventricle, within the tectum, basal forebrain, archistriatum, and caudal neostriatum, and in the hippocampus. These latter populations have not been described in other avian species and resemble features of the catecholamine system generally found in either reptiles or mammals.

A novel reduced intensity regimen for allogeneic hematopoietic stem cell transplantation associated with a reduced incidence of graft-versus-host disease.

SUMMARY: In all, 55 patients at high risk or ineligible for a conventional allogeneic hematopoietic stem cell transplant (HSCT) received a regimen consisting of extracorporeal photopheresis, pentostatin, and reduced dose total body irradiation. The median age was 49 years (18-70 years); 44 received a sibling and 11 an unrelated HSCT; 44% were over the age of 50 years and 31% had undergone a prior HSCT. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. Full donor chimerism was documented in 98% by day +100. The 1000-day nonrelapse mortality was 11%. The median follow-up is 502 days (154-1104 days). The 1- and 2-year overall survival (OS) and event-free survival (EFS) are 67, 58 and 55%, and 47%, respectively. Patients who had not received a prior HSCT or had less than three prior chemotherapy regimens had a 71% OS and 67% EFS at 1 year. Greater than grade II aGVHD developed in 9% and chronic GVHD (cGVHD) in 43%, and extensive in 12% and limited in 31%. Of the patients, 86% who engrafted had a disease response, 72% had complete and 14% partial responses. This novel reduced intensity preparative regimen was well tolerated and associated with a low incidence of transplant-related mortality and serious acute and cGVHD.

Distribution of iron in the parrot brain: conserved (pallidal) and derived (nigral) labeling patterns.

The distribution of iron in the brain of a vocal learning parrot, the budgerigar (Melopsittacus undulatus), was examined using iron histochemistry. In mammals, iron is a highly specific stain for the dorsal and ventral pallidal subdivision as well as specific cell groups in the brainstem, including the substantia nigra pars reticulata [Neuroscience 11 (1984) 595-603]. The purpose of this study was to compare the distribution of iron in the mammalian and avian brain focusing on pallidal and nigral cell groups. The results show that in the avian brain, iron stains oligodendrocytes, neurons and the neuropil. Cell staining changes dramatically along the rostrocaudal axis, with neuronal labeling confined to regions caudal to the thalamus and oligodendrocyte labeling denser in regions rostral to the dorsal thalamus. Many sensory forebrain regions contain appreciable iron labeling, including telencephalic vocal control nuclei. The dorsal and ventral subdivision of the avian pallidum, along with the basal ganglia component of the vocal control circuit, the magnicellular nucleus of the lobus parolfactorius, stain heavily for iron. Several brainstem regions, including nucleus rotundus, the medial spiriform nucleus (SpM), the principle nucleus of the trigeminal nerve, nucleus laminaris and scattered cell groups throughout the isthmus and pontine reticular formation stain intensely for iron. Within SpM neuronal labeling is more intense in the medial division while oligodendrocyte labeling is more intense in the lateral division. surprisingly no nigral iron staining was observed. Our results imply that iron is a conserved marker for the pallidum in birds and mammals, but that patterns of nigral staining have diverged in birds and mammals. Differences in iron staining patterns between birds and mammals may also reflect the relatively greater importance of the collothalamic visual pathways, pretectal-cerebellar pathways and specialized vocal learning circuitry in avian sensory and motor processing.

Immunomodulatory effects of extracorporeal photochemotherapy in patients with extensive chronic graft-versus-host disease.

Extracorporeal photochemotherapy (ECP) has been associated with clinical improvement in several patients with acute and chronic graft-versus-host disease (cGVHD) after allogeneic bone marrow transplantation, but the mechanism of action is unknown. This study tested the hypothesis that in patients with cGVHD, ECP modulates alloreactivity by affecting activated lymphocyte populations or by altering the interaction between effector lymphocytes and antigen-presenting cells (APCs). Ten patients who had refractory cGVHD were treated with ECP, and the clinical response to and immunologic effects of this therapy were assessed. Seven patients had a response and 3 had no change in clinical manifestations of cGVHD. One patient died from catheter-related sepsis. Immunologic effects observed after ECP included normalization of inverted ratios of CD4 to CD8 cells, an increase in the number of CD3-CD56+ natural killer (NK) cells, and a decrease in CD80+ and CD123+ circulating dendritic cells. The results suggest that ECP modulates both NK cells and APC populations in patients with cGVHD.

Cytoarchitecture of vocal control nuclei in nestling budgerigars: relationships to call development.

Changes in the cytoarchitecture of vocal control nuclei were investigated in nestling budgerigars (Melopsittacus undulatus) from hatching to fledging (five to six weeks) in relation to changes in vocalizations produced by nestlings during this period. The nuclei investigated were the hypoglossal nucleus, dorsomedial nucleus of the intercollicular midbrain, central nucleus of the archistriatum, central nucleus of the lateral neostriatum, oval nucleus of the hyperstriatum ventrale, medial division of the oval nucleus of the anterior neostriatum, and magnocellular nucleus of the lobus parolfactorius. These nuclei have been shown to form functional circuits in adults related to vocal learning. Consistent with previously reported results, we found that call development could be described in terms of five different phases based on changes in the duration and segmentation of single and multiple segment food begging calls and the appearance of the first socially learned contact calls around the time of fledging. We also found that call segment duration exhibited an inverted U-shaped developmental function during the nestling period, as has been found for total call duration. Cytoarchitectonic studies revealed striking changes in the cellular architecture of vocal control nuclei during the first four weeks posthatching. At hatching the hypoglossal nucleus exhibits adult-like cytoarchitecture, and the central nucleus of the archistriatum and the central nucleus of the lateral neostriatum are distinguishable from surrounding fields. By one week posthatch, the central nucleus of the archistriatum exhibits an adult-like appearance, while other telencephalic vocal control nuclei do not exhibit adult-like cytoarchitecture until three to four weeks posthatching. By two weeks posthatching, the dorsomedial nucleus of the intercollicular midbrain also exhibits adult-like cytoarchitecture. We observed substantial decreases in the thickness of ventricular proliferation zones during this period, with decreases in ventricular zones occurring at about the same point that nuclei at corresponding levels come to exhibit adult-like cytoarchitectonic features. Of interest is the fact that cytoarchitectural development occurs asynchronously in different brain regions, with the appearance of adult-like characteristics in the hindbrain and midbrain occurring before the appearance of adult-like cytoarchitectonic characteristics in telencephalic nuclei. These results are consistent with recent lesion studies indicating that neither auditory feedback nor telencephalic vocal control nuclei are necessary for the production of food begging and other nestling calls until three to four weeks posthatching.