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Obscure
Terms modified by Obscure Selected AbstractsAbnormal giant cells in the cerebral lesions of tuberous sclerosis complexCONGENITAL ANOMALIES, Issue 1 2007Masashi Mizuguchi ABSTRACT Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations of either of the two tumor suppressor genes, TSC1 and TSC2, encoding hamartin and tuberin, respectively. TSC is pathologically characterized by the occurrence of multiple hamartias (focal dysplasias) and hamartomas (benign tumors) in the brain and many other organs. Cortical tubers are hamartias in the cerebral cortex responsible for many neuropsychiatric symptoms of TSC. Unlike TSC-associated hamartomas, cortical tubers do not result from second somatic mutations of the TSC gene, and the mechanism by which they occur remains obscure. Histologically, the most conspicuous feature of cortical tubers is the presence of abnormal giant cells, which show abnormal size and differentiation. Recent studies on human TSC and its animal models have elucidated the critical roles of hamartin and tuberin regulating the growth and differentiation of neural cells. [source] Understanding the Causes of Disease in European Freshwater CrayfishCONSERVATION BIOLOGY, Issue 6 2004BRETT F. EDGERTON Aphanomyces astaci; bioseguridad; epizootia; langostinos de agua dulce; patología de langostinos; peste de langostinos Abstract:,Native European freshwater crayfish (Astacida, Decapoda) are under severe pressure from habitat alteration, the introduction of nonindigenous species, and epizootic disease. Crayfish plague, an acute disease of freshwater crayfish caused by the fungus-like agent Aphanomyces astaci, was introduced into Europe in the mid-nineteenth century and is responsible for ongoing widespread epizootic mortality in native European populations. We reviewed recent developments and current practices in the field of crayfish pathology. The severity of crayfish plague has resulted in an overemphasis on it. Diagnostic methods for detecting fungi and fungal-like agents, and sometimes culturing them, are frequently the sole techniques used to investigate disease outbreaks in European freshwater crayfish. Consequently, the causes of a significant proportion of outbreaks are undetermined. Pathogen groups well known for causing disease in other crustaceans, such as viruses and rickettsia-like organisms, are poorly understood or unknown in European freshwater crayfish. Moreover, the pathogenic significance of some long-known pathogens of European freshwater crayfish remains obscure. For effective management of this culturally significant and threatened resource, there is an urgent need for researchers, diagnosticians, and resource managers to address the issue of disease in European freshwater crayfish from a broader perspective than has been applied previously. Resumen:,Los langostinos nativos de Europa (Astacida, Decapada) están bajo severa presión por alteración del hábitat, la introducción de especies no nativas y una enfermedad epizoótica. La peste de langostinos, una enfermedad aguda de langostinos de agua dulce producida por el agente micoide Aphanomyces astaci, fue introducida a Europa a mediados del siglo diecinueve y es responsable de la actual mortalidad epizoótica de poblaciones Europeas nativas. Revisamos acontecimientos recientes y prácticas actuales en el campo de la patología de langostinos. La severidad de la peste de langostinos ha resultado en un excesivo énfasis en ella. Los métodos para diagnosticar, y algunas veces cultivar, hongos y agentes micoides frecuentemente son la única técnica empleada al investigar brotes de la enfermedad en langostinos de agua dulce en Europa. Consecuentemente, no están determinadas las causas de una proporción significativa de los brotes. Grupos patógenos, como virus y organismos similares a rickettsias, bien conocidos por producir enfermedades en otros crustáceos son poco o nada conocidos en langostinos de agua dulce de Europa. Más aún, el significado patogénico de algunos patógenos de langostinos de agua dulce de Europa largamente conocidos es oscuro. Para el manejo efectivo de este recurso culturalmente significativo y amenazado es urgente la necesidad de investigadores, diagnosticadores y gestores de recursos para atender el asunto de la enfermedad en langostinos de agua dulce europeos desde una perspectiva más amplia que la previamente aplicada. [source] Nail Biopsy: Assessment of Indications and OutcomeDERMATOLOGIC SURGERY, Issue 2 2005Chander Grover MD, MNAMS Background For years, nail biopsy has been shunned as a difficult and scarring procedure, which is seldom required in day-to-day practice. Only a few studies with a limited number of patients have been carried out to assess its utility in dermatology. Methods We studied 270 patients with nail disorders (both infectious and noninfectious). In 205 cases, the clinical diagnosis could be confirmed with the help of routine diagnostic aids, in the form of potassium hydroxide preparation, fungal culture, and biopsy of associated skin lesions. In the remaining 65 cases, various types of nail biopsies were carried out after ruling out contraindications to nail surgery. Results Overall, the histopathologic changes were found to be diagnostic in 63% of cases. Findings were more characteristic in infectious disorders of the nail unit. The diagnostic yield varied with the type of biopsy procedure. Side effects in the form of scarring and nail dystrophy were seen in 29.2% of the patients. Discussion Nail biopsy is useful, especially in cases with isolated nail involvement, an absence of skin lesions, and disorders such as twenty-nail dystrophy. It should be advocated in cases in which the routine diagnostic procedures fail to yield results. Proper selection of cases, choice of biopsy technique, and attention to the surgical procedure help in minimizing the side effects associated with the procedure. Conclusion Nail biopsy was found to be a simple, safe, and useful procedure, especially in cases in which the clinical diagnosis is otherwise obscure. CHANDER GROVER, MD, DNB, MNAMS, SONI NANDA, MD, B. S. N. REDDY, MD, MNAMS, AND KRISHNAMOORTHY UMA CHATURVEDI, MD, HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPPORTERS. [source] Characterization and expression of AmphiBMP3,/3b gene in amphioxus Branchiostoma japonicumDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 2 2010Yi Sun Bone morphogenetic proteins (BMPs) are responsible for regulating embryo development and tissue homeostasis beyond osteogenesis. However, the precise biological roles of BMP3 and BMP3b remain obscure to a certain extent. In the present study, we cloned an orthologous gene (AmphiBMP3/3b) from amphioxus (Branchiostoma japonicum) and found its exon/intron organization is highly conserved. Further, in situ hybridization revealed that the gene was strongly expressed in the dorsal neural plate of the embryos. The gene also appeared in Hatschek's left diverticulum, neural tube, preoral ciliated pit and gill slit of larvae, and adult tissues including ovary, neural tube and notochordal sheath. Additionally, real-time quantitative polymerase chain reaction (RTqPCR) analysis revealed that the expression displayed two peaks at gastrula and juvenile stages. These results indicated that AmphiBMP3/3b, a sole orthologue of vertebrate BMP3 and BMP3b, might antagonize ventralizing BMP2 orthologous signaling in embryonic development, play a role in the evolutionary precursors of adenohypophysis, as well as act in female ovary physiology in adult. [source] Rapid accumulation of nucleostemin in nucleolus during newt regenerationDEVELOPMENTAL DYNAMICS, Issue 4 2007Nobuyasu Maki Abstract In newt regeneration, differentiated cells can revert to stem cell,like cells in which the proliferative ability and multipotentiality are restored after dedifferentiation. However, the molecular events that occur during the dedifferentiation still remain obscure. Nucleostemin has been identified in mammals as a nucleolar protein specific to stem cells and cancer cells. In this study, a newt nucleostemin homologue was cloned and its regulation was analyzed. During lens regeneration, the expression of nucleostemin was activated and nucleostemin rapidly accumulated in the nucleoli of dedifferentiating pigmented epithelial cells 2 days before cell cycle reentry. During limb regeneration, nucleostemin also accumulated in the nucleoli of degenerating multinucleate muscle fibers before blastema formation. These findings suggest that nucleostemin plays a role in the dedifferentiation of newt cells and can provide crucial clues for addressing the molecular events at early steps of cellular dedifferentiation in newts. Developmental Dynamics 236:941,950, 2007. © 2006 Wiley-Liss, Inc. [source] Villin: A marker for development of the epithelial pyloric borderDEVELOPMENTAL DYNAMICS, Issue 1 2002Evan M. Braunstein Abstract In the adult gastrointestinal tract, the morphologic borders between esophagus and stomach and between stomach and small intestine are literally one cell thick. The patterning mechanisms that underlie the development of these sharp regional divisions from a once continuous endodermal tube are still obscure. In the embryonic endoderm of the developing gut, region-specific expression of certain genes (e.g., intestine-specific expression of the actin bundling protein villin) can be detected as early as 9.0 days post coitum, although the morphologic differentiation of the gut epithelium proper does not begin until 4 to 5 days later. By using a mouse model in which a ,-galactosidase marker has been inserted into the endogenous villin locus, we examined the development of the stomach/intestinal (pyloric) border during gut organogenesis. The data indicate that the border is not sharp from the outset. Rather, the initial border region is characterized by a decreasing gradient of villin/,-galactosidase expression that extends into the distal stomach. A sharp epithelial border of villin/,-galactosidase expression appears abruptly at day 16 and is further refined over the next 3 weeks to form the distinct one-cell-thick border characteristic of the adult. These results indicate that an important previously unrecognized patterning event occurs in the gut epithelium at 16 days; this event may define an epithelial compartment boundary between the stomach and the intestine. The villin/,-galactosidase mouse model characterized here provides an excellent substrate with which to further dissect the mechanisms involved in this patterning process. © 2002 Wiley-Liss, Inc. [source] Outcome after prolonged convulsive seizures in 186 children: low morbidity, no mortalityDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 1 2004Piia Metsäranta BM Prolonged convulsive seizures are a common neurological emergency and a potential cause of neuronal damage and functional sequelae. We explored the role of seizure duration and various background factors for neurological sequelae in children with prolonged convulsive seizures. The population-base of this study was all children (age < 16 years) who had been admitted to the Tampere University Hospital, Finland between 1993 and 1999 with convulsive seizures lasting more than 5 minutes. Patients were followed up individually (mean length of follow-up 2 years 1 month, range 0 to 7 years 8 months). All available data on the prolonged seizure episodes and clinical follow-up were analyzed retrospectively by a detailed review of all medical charts and records. In 186 children (94 males, 92 females; mean age 4 years 5 months, SD 3 years 10 months, range 1 month to 15 years 4 months) there were 279 separate convulsive seizure episodes lasting over 5 minutes, yielding an annual incidence of 47.5 out of every 100000 episodes. Seizure aetiology was idiopathic in 26.2% of episodes, febrile in 41.9%, remote symptomatic in 28%, and acute symptomatic in 3.9% of episodes. Mean duration of all seizure episodes was 42.5 minutes (SD 46.1 minutes) and was significantly correlated with the aetiology: shortest in the febrile group (mean 35.4 minutes) and longest in the acute symptomatic group (mean 88.6 minutes; p < 0.001). There was no mortality related directly to these acute seizure episodes. The most common sequela was an onset of epilepsy in 40 children (22%). Permanent neurological sequelae were noted in only four patients (2.2%; mean seizure duration 16 minutes) and non-permanent sequelae in six patients (3.2%; mean seizure duration 38 minutes). Neurological sequelae of prolonged convulsive seizures in children are rare and are related to aetiological factors rather than the duration of a single seizure. The role of acute seizures in the evolution of epilepsy in children remains obscure. [source] Activity of nAChRs containing ,9 subunits modulates synapse stabilization via bidirectional signaling programsDEVELOPMENTAL NEUROBIOLOGY, Issue 14 2009Vidya Murthy Abstract Although the synaptogenic program for cholinergic synapses of the neuromuscular junction is well known, little is known of the identity or dynamic expression patterns of proteins involved in non-neuromuscular nicotinic synapse development. We have previously demonstrated abnormal presynaptic terminal morphology following loss of nicotinic acetylcholine receptor (nAChR) ,9 subunit expression in adult cochleae. However, the molecular mechanisms underlying these changes have remained obscure. To better understand synapse formation and the role of cholinergic activity in the synaptogenesis of the inner ear, we exploit the nAChR ,9 subunit null mouse. In this mouse, functional acetylcholine (ACh) neurotransmission to the hair cells is completely silenced. Results demonstrate a premature, effusive innervation to the synaptic pole of the outer hair cells in ,9 null mice coinciding with delayed expression of cell adhesion proteins during the period of effusive contact. Collapse of the ectopic innervation coincides with an age-related hyperexpression pattern in the null mice. In addition, we document changes in expression of presynaptic vesicle recycling/trafficking machinery in the ,9 null mice that suggests a bidirectional information flow between the target of the neural innervation (the hair cells) and the presynaptic terminal that is modified by hair cell nAChR activity. Loss of nAChR activity may alter transcriptional activity, as CREB binding protein expression is decreased coincident with the increased expression of N-Cadherin in the adult ,9 null mice. Finally, by using mice expressing the nondesensitizing ,9 L9,T point mutant nAChR subunit, we show that increased nAChR activity drives synaptic hyperinnervation. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009 [source] Pre-/post-otic rhombomeric interactions control the emergence of a fetal-like respiratory rhythm in the mouse embryoDEVELOPMENTAL NEUROBIOLOGY, Issue 12 2006C. Borday Abstract How regional patterning of the neural tube in vertebrate embryos may influence the emergence and the function of neural networks remains elusive. We have begun to address this issue in the embryonic mouse hindbrain by studying rhythmogenic properties of different neural tube segments. We have isolated pre- and post-otic hindbrain segments and spinal segments of the mouse neural tube, when they form at embryonic day (E) 9, and grafted them into the same positions in stage-matched chick hosts. Three days after grafting, in vitro recordings of the activity in the cranial nerves exiting the grafts indicate that a high frequency (HF) rhythm (order: 10 bursts/min) is generated in post-otic segments while more anterior pre-otic and more posterior spinal territories generate a low frequency (LF) rhythm (order: 1 burst/min). Comparison with homo-specific grafting of corresponding chick segments points to conservation in mouse and chick of the link between the patterning of activities and the axial origin of the hindbrain segment. This HF rhythm is reminiscent of the respiratory rhythm known to appear at E15 in mice. We also report on pre-/post-otic interactions. The pre-otic rhombomere 5 prevents the emergence of the HF rhythm at E12. Although the nature of the interaction with r5 remains obscure, we propose that ontogeny of fetal-like respiratory circuits relies on: (i) a selective developmental program enforcing HF rhythm generation, already set at E9 in post-otic segments, and (ii) trans-segmental interactions with pre-otic territories that may control the time when this rhythm appears. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source] Conflict, trade and the medium-term future of food security in SudanDISASTERS, Issue 2007David Keen Recent economic growth and the Comprehensive Peace Agreement (CPA) have both been seen as grounds for optimism about the future of food security in Sudan. However, solving the North- South conflict (if indeed it is solved) does not resolve conflicts within either the North or the South and may even encourage a variety of conflicts. The classic neoliberal prescription of peace, growth and foreign investment may deepen (and obscure) the needs and grievances of those who have historically been left behind in a dysfunctional development process. Historically, some of those marginalised by patterns of development in Sudan have chosen to rebel, while others have had their grievances diverted against those even more marginal than themselves. Dysfunctional and violent processes of development must be reversed. They cannot be adequately compensated for-but may be legitimised-by attempts to use food aid as a ,safety net'. Meanwhile, those who benefited from war may have incentives to derail the peace. [source] Impact of Left Ventricular Function on the Pulmonary Vein Doppler Spectrum:ECHOCARDIOGRAPHY, Issue 1 2003Nonsimultaneous Assessment with Load-Insensitive Indices Pulmonary vein Doppler spectrum is highly load-dependent and thus has been used to estimate left ventricular (LV) filling pressure. However, the impact of LV function on pulmonary vein Doppler spectrum remains obscure because only load-sensitive indices were studied previously. In the present study, measurements of the pulmonary vein Doppler spectrum were correlated with load-insensitive LV systolic (end-systolic elastance [Ees]) and diastolic (relaxation time constant [tau] and beta coefficient of the end-diastolic pressure volume relationship) function indices obtained from an invasive catheterization study nonsimultaneously. The peak velocity, velocity time integral, and duration of systolic forward spectrum were significantly correlated with Ees (r = 0.35, r = 0.36, andr = 0.41, respectively;P < 0.05). The pulmonary vein diastolic velocity time integral (PVDVTI) and duration of the diastolic forward spectrum were significantly correlated with Ees (r = 0.51andr = 0.57, respectively;P < 0.01). PVDVTI was correlated with tau and the end-diastolic pressure-volume relationship (EDPVR) (r = 0.42andr = 0.40respectively,P < 0.05). On the other hand, the systolic fraction of the forward spectrum was significantly correlated with ejection fraction (for peak velocity,r = 0.63, P < 0.01; for velocity time integral,r = 0.37, P < 0.05) but not with Ees, and the diastolic fraction of the forward spectrum was significantly correlated with minimum pressure derivative over time (for peak velocity,r = 0.48, P < 0.05; for velocity time integral,r = 0.44, P < 0.05, respectively) but not with tau or EDPVR. In summary, the systolic and diastolic components of the pulmonary vein Doppler spectrum are affected variably by LV systolic and diastolic function, independent of the loading condition. The systolic and diastolic fraction of pulmonary vein Doppler spectrum appears to depend more on the loading condition than the LV systolic or diastolic function. (ECHOCARDIOGRAPHY, Volume 20, January 2003) [source] Effects of co-culture of amoebae with indoor microbes on their cytotoxic and proinflammatory potentialENVIRONMENTAL TOXICOLOGY, Issue 4 2007Terhi Yli-Pirilä Abstract Free-living amoebae are ubiquitous environmental protozoa found in both natural and man-made environments, including moisture-damaged buildings. Furthermore, the interaction between amoebae and bacteria has been shown to enhance the virulence and pathogenicity of some bacteria. While the inhabitants of moisture damaged buildings are known to be at risk of suffering adverse health effects, the exact causative agents and mechanisms are still obscure. To examine the possible role of amoebae in the health effects associated with moisture damages, the effects of amoebae on the cytotoxicity and proinflammatory potential of nonpathogenic microbes common in moisture-damaged buildings were investigated. First, two bacterial and three fungal strains were cultured both individually and in coculture with Acanthamoeba polyphaga. Then, mouse RAW264.7 macrophages were exposed to the cocultures as well as the individually grown bacteria, fungi, and amoebae. Finally, cell viability and production of proinflammatory mediators, i.e., nitric oxide (NO), tumor necrosis factor , (TNF-,), and interleukin 6 (IL-6), were measured in macrophages after the exposure. The results revealed that cocultivation with amoebae increased the cytotoxicity of the bacterium Streptomyces californicus and the fungus Penicillium spinulosum. Moreover, the macrophages produced up to 10 times higher concentrations of NO after the exposure to these cocultures than after the exposure to individually grown microbes. Finally, the production of the cytokines was up to two orders of magnitude higher (IL-6) and up to four times higher (TNF-,) after exposure to the cocultures when compared to individually grown microbes. We conclude that amoebae are able to potentiate the cytotoxicity and proinflammatory properties of certain microbes associated with moisture damages. © 2007 Wiley Periodicals, Inc. Environ Toxicol 22: 357,367, 2007. [source] Caloric Restriction Inhibits Seizure Susceptibility in Epileptic EL Mice by Reducing Blood GlucoseEPILEPSIA, Issue 11 2001Amanda E. Greene Summary: ,Purpose: Caloric restriction (CR) involves underfeeding and has long been recognized as a dietary therapy that improves health and increases longevity. In contrast to severe fasting or starvation, CR reduces total food intake without causing nutritional deficiencies. Although fasting has been recognized as an effective antiseizure therapy since the time of the ancient Greeks, the mechanism by which fasting inhibits seizures remains obscure. The influence of CR on seizure susceptibility was investigated at both juvenile (30 days) and adult (70 days) ages in the EL mouse, a genetic model of multifactorial idiopathic epilepsy. Methods: The juvenile EL mice were separated into two groups and fed standard lab chow either ad libitum (control, n = 18) or with a 15% CR diet (treated, n = 17). The adult EL mice were separated into three groups; control (n = 15), 15% CR (n = 6), and 30% CR (n = 3). Body weights, seizure susceptibility, and the levels of blood glucose and ketones (,-hydroxybutyrate) were measured over a 10-week treatment period. Simple linear regression and multiple logistic regression were used to analyze the relations among seizures, glucose, and ketones. Results: CR delayed the onset and reduced the incidence of seizures at both juvenile and adult ages and was devoid of adverse side effects. Furthermore, mild CR (15%) had a greater antiepileptogenic effect than the well-established high-fat ketogenic diet in the juvenile mice. The CR-induced changes in blood glucose levels were predictive of both blood ketone levels and seizure susceptibility. Conclusions: We propose that CR may reduce seizure susceptibility in EL mice by reducing brain glycolytic energy. Our preclinical findings suggest that CR may be an effective antiseizure dietary therapy for human seizure disorders. [source] The controversial relationship between NLRP3, alum, danger signals and the next-generation adjuvantsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2010Roberto Spreafico Abstract Alum has been the only adjuvant licensed for human vaccines for decades and is still widely used, but its mechanism of action remains obscure. Recently, the NLRP3 inflammasome has been linked to the immunostimulatory properties of alum and other particulate adjuvants, although it is disputed to what degree NLRP3 is genuinely essential in vivo. Meanwhile, researchers are testing adjuvants harnessing both the infectious/non-infectious-discriminating TLR and the danger-sensing NLRP3 inflammasome pathways. Could this be the basis of a long-needed rationale in the design of adjuvants? [source] Activating and inhibitory Fc, receptors can differentially modulate T cell-mediated autoimmunityEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2008Mirentxu Abstract The molecular bases responsible for the loss of T cell tolerance to myelin antigens leading to the onset of multiple sclerosis remain obscure. It has been shown that balanced signaling through activating and inhibitory receptors is critical for the maintenance of tolerance to self antigens in autoimmune disorders. However, although Fc,R have been shown to influence experimental autoimmune encephalomyelitis (EAE) development, their role during pathogenesis remains controversial. Here we have evaluated whether relative expression of activating (Fc,RIII) and inhibitory (Fc,RIIb) Fc,R can modulate myelin-specific T cell response, as well as the susceptibility to develop EAE in mice. While Fc,RIIb,/, mice showed a significant increase in EAE severity, an Fc,RIII deficiency protected mice from disease. In addition, Fc,RIIb,/, mice showed enhanced activation of myelin-specific effector T cells, which were significantly more effective at causing EAE in adoptive transfer experiments than were T cells from wild-type mice. In contrast, Fc,RIII,/, mice showed a significantly reduced activation of myelin-specific T cells and these cells failed to adoptively transfer EAE. Consistently, increased expansion of regulatory T cells (Treg) during EAE was observed only for Fc,RIII,/, mice, which were able to suppress disease when adoptively transferred to recipient mice. These findings suggest that the balance between activating and inhibitory Fc,R signaling can contribute to the maintenance of T cell tolerance to myelin antigens and modulate EAE progression. [source] Staying alive , naïve CD4+ T cell homeostasisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2007Jared F. Purton Abstract The immune system must maintain a broad repertoire of naïve T cells in order to respond to the diverse range of pathogens that it will encounter over the course of a lifetime. Although it is known that contact with IL-7 is crucial for the survival of naïve T cells, the precise intracellular signals that mediate its effects remain obscure. An article in this issue of the European Journal of Immunology has found that IL-7 requires the coordinated action of multiple pathways to maintain naïve CD4+ T cells. See accompanying article: http://dx.doi.org/10.1002/eji.200737234 [source] Chronic cocaine sensitizes striatal GABAergic synapses to the stimulation of cannabinoid CB1 receptorsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2007Diego Centonze Abstract Behavioural studies indicate that cannabinoid receptors are implicated in cocaine addiction. The synaptic underpinning of cocaine,cannabinoid receptor interaction is however, obscure. We have studied electrophysiologically the sensitivity of cannabinoid receptors modulating synaptic transmission in the striatum of rats exposed to cocaine. One-day treatment with cocaine did not modify the synaptic response to HU210, a cannabinoid CB1 receptor agonist. Seven days cocaine-treatment, conversely, caused conditioned place preference, and sensitized striatal GABAergic synapses to the presynaptic effect of cannabinoid CB1 receptor stimulation. The cannabinoid receptor-induced modulation of glutamate transmission was unaltered by cocaine. Furthermore, the effects of chronic cocaine on cannabinoid-mediated regulation of striatal GABA synapses were attenuated one week after the discontinuation of cocaine, and absent two weeks later, indicating the progressive reversibility of the adaptations of cannabinoid system during abstinence of drug consumption. Our data support the concept that modulation of cannabinoid receptors might be useful against drug abuse. [source] DIVERSIFICATION OF THE AFRICAN GENUS PROTEA (PROTEACEAE) IN THE CAPE BIODIVERSITY HOTSPOT AND BEYOND: EQUAL RATES IN DIFFERENT BIOMESEVOLUTION, Issue 3 2010Luis M. Valente The Cape region of South Africa is a hotspot of flowering plant biodiversity. However, the reasons why levels of diversity and endemism are so high remain obscure. Here, we reconstructed phylogenetic relationships among species in the genus Protea, which has its center of species richness and endemism in the Cape, but also extends through tropical Africa as far as Eritrea and Angola. Contrary to previous views, the Cape is identified as the ancestral area for the radiation of the extant lineages: most species in subtropical and tropical Africa are derived from a single invasion of that region. Moreover, diversification rates have been similar within and outside the Cape region. Migration out of the Cape has opened up vast areas, but those lineages have not diversified as extensively at fine spatial scales as lineages in the Cape. Therefore, higher net rates of diversification do not explain the high diversity and endemism of Protea in the Cape. Instead, understanding why the Cape is so diverse requires an explanation for how Cape species are able to diverge and persist at such small spatial scales. [source] FMRFamide gene and peptide expression during central nervous system development of the cephalopod mollusk, Idiosepius notoidesEVOLUTION AND DEVELOPMENT, Issue 2 2010Tim Wollesen SUMMARY Mollusks are a showcase of brain evolution represented by several classes with a varying degree of nervous system centralization. Cellular and molecular processes involved in the evolution of the highly complex cephalopod brain from a simple, monoplacophoran-like ancestor are still obscure and homologies on the cellular level are poorly established. FMRFamide (Phe-Ile-Arg-Phe-NH2)-related peptides (FaRPs) constitute an evolutionarily conserved and diverse group of neuropeptides in the central nervous system (CNS) of many metazoans. Herein, we provide a detailed description of the developing FMRFamide-like immunoreactive (Fa-lir) CNS of the pygmy squid Idiosepius notoides using gene expression analyses and immunocytochemistry. The open reading frame of the I. notoides FMRFamide gene InFMRF predicts one copy each of FIRFamide, FLRFamide (Phe-Leu-Arg-Phe-NH2), ALSGDAFLRFamide (Ala-Leu-Ser-Gly-Asp-Ala-Phe-Leu-Arg-Phe-NH2), and 11 copies of FMRFamide. Applying matrix-assisted laser desorption/ionization time-of-flight (ToF) mass spectrometry-based peptide profiling, we characterized all predicted FaRPs except ALSGDAFLRFamide. Two cell clusters express InFMRF and show FMRFamide-like-immunoreactivity within the palliovisceral ganglia, that is, the future posterior subesophageal mass, during the lobe differentiation phase. They project neurites via ventral axonal tracts, which form the scaffold of the future subesophageal mass. In the supraesophageal mass, InFMRF is first expressed during mid-embryogenesis in the superior and inferior buccal lobes. A neurite of the peduncle commissure represents the first Fa-lir element. Later, the sub- and supraesophageal mass interconnect via Fa-lir neurites and more brain lobes express InFMRF and FMRFamide-like peptides. InFMRF expression was observed in fewer brain lobes than Fa-lir elements. The early expression of InFMRF and FMRFamide-lir peptides in the visceral system and not the remaining CNS of the cephalopod I. notoides resembles the condition found in the majority of investigated gastropods. [source] The 21st century renaissance of the basophil?EXPERIMENTAL DERMATOLOGY, Issue 11 2006Current insights into its role in allergic responses, innate immunity Abstract:, Basophils and mast cells express all the three subchains of the high-affinity immunoglobulin E (IgE) receptor Fc,RI and contain preformed histamine in the cytoplasmic granules. However, it is increasingly clear that these cells play distinct roles in allergic inflammatory disease. Despite their presence throughout much of the animal kingdom, the physiological function of basophils remains obscure. As rodent mast cells are more numerous than basophils, and generate an assortment of inflammatory cytokines, basophils have often been regarded as minor players in allergic inflammation. In humans, however, basophils are the prime early producers of interleukin (IL)-4 and IL-13, T helper (Th)2-type cytokines crucial for initiating and maintaining allergic responses. Basophils also express CD40 ligand which, in combination with IL-4 and IL-13, facilitates IgE class switching in B cells. They are the main cellular source for early IL-4 production, which is vital for the development of Th2 responses. The localization of basophils in various tissues affected by allergic inflammation has now been clearly demonstrated by using specific staining techniques and the new research is shedding light on their selective recruitment to the tissues. Finally, recent studies have shown that basophil activation is not restricted to antigen-specific IgE crosslinking, but can be caused in non-sensitized individuals by a growing list of parasitic antigens, lectins and viral superantigens, binding to non-specific IgE antibodies. This, together with novel IgE-independent routes of activation, imparts important new insights into the potential role of basophils in both adaptive and innate immunity. [source] The effect of ultraviolet B irradiation on nitric oxide synthase expression in murine keratinocytesEXPERIMENTAL DERMATOLOGY, Issue 6 2000M. Sasaki Abstract: Nitric oxide (NO), which has several physiological functions in skin, is generated by NO synthase (NOS). NOS has at least three isoforms; endothelial NOS (eNOS), brain NOS (bNOS), and inducible NOS (iNOS). Ultraviolet B (UVB) irradiation has been reported to stimulate NO production in skin via induction or activation of NOS, however, the exact mechanism of NOS induction by UVB irradiation remains obscure. In this study, we investigated the direct effect of UVB on the expression of NOS isoforms in murine keratinocytes, and found a significant increase in NO production within 48 h. mRNA and protein expressions of bNOS were both enhanced by UVB irradiation in murine keratinocytes, whereas iNOS mRNA expression was suppressed at 4 and 12 h after UVB irradiation. These results suggest that the enhancement of NO production observed after UVB irradiation in murine keratinocytes may be explained in part by the upregulation of bNOS expression, but not iNOS expression. [source] Women's working wardrobes: a study using card sortsEXPERT SYSTEMS, Issue 3 2005Sue Gerrard Abstract: Picture sorts were used to investigate perceptions of women's office clothes, with a sample of ten male and ten female subjects who normally worked in an office environment. The pictures on the cards were taken from catalogues, and showed women's outfits which might be worn in an office. The subjects sorted the cards repeatedly and generated criteria and categories of their own choice. Some of the criteria and categories had not been previously reported in the clothing research literature. Over half of the male subjects, but none of the female subjects, used ,married/unmarried woman' as a sorting criterion, although only one of the images sorted showed a wedding ring. A significantly higher proportion of male than of female subjects used dichotomous categorization (i.e. sorting the cards into two piles for one or more of the criteria). The reasons for this are obscure, but do not appear to be a simple outcome of males not knowing much about female clothing. Previous research into clothing has tended to involve researcher-centred approaches such as semiotics; the results from this study suggest that there would be advantages in wider use of subject-centred approaches such as card sorts, both in this domain and elsewhere. It was concluded that card sorts were a useful method and should be more widely used. [source] Oxygen binding and its allosteric control in hemoglobin of the primitive branchiopod crustacean Triops cancriformisFEBS JOURNAL, Issue 13 2007Ralph Pirow Branchiopod crustaceans are endowed with extracellular, high-molecular-mass hemoglobins (Hbs), the functional and allosteric properties of which have largely remained obscure. The Hb of the phylogenetically ancient Triops cancriformis (Notostraca) revealed moderate oxygen affinity, cooperativity and pH dependence (Bohr effect) coefficients: P50 = 13.3 mmHg, n50 = 2.3, and , = ,0.18, at 20 °C and pH 7.44 in Tris buffer. The in vivo hemolymph pH was 7.52. Bivalent cations increased oxygen affinity, Mg2+ exerting a greater effect than Ca2+. Analysis of cooperative oxygen binding in terms of the nested Monod,Wyman,Changeux (MWC) model revealed an allosteric unit of four oxygen-binding sites and functional coupling of two to three allosteric units. The predicted 2 × 4 and 3 × 4 nested structures are in accord with stoichiometric models of the quarternary structure. The allosteric control mechanism of protons comprises a left shift of the upper asymptote of extended Hill plots which is ascribable to the displacement of the equilibrium between (at least) two high-affinity (relaxed) states, similar to that found in extracellular annelid and pulmonate molluscan Hbs. Remarkably, Mg2+ ions increased oxygen affinity solely by displacing the equilibrium between the tense and relaxed conformations towards the relaxed states, which accords with the original MWC concept, but appears to be unique among Hbs. This effect is distinctly different from those of ionic effectors (bivalent cations, protons and organic phosphates) on annelid, pulmonate and vertebrate Hbs, which involve changes in the oxygen affinity of the tense and/or relaxed conformations. [source] A novel Takeout-like protein expressed in the taste and olfactory organs of the blowfly, Phormia reginaFEBS JOURNAL, Issue 18 2006Kazuyo Fujikawa In insects, the functional molecules responsible for the taste system are still obscure. The gene for a 28.5 kDa protein purified from taste sensilla of the blowfly Phormia regina belongs to a gene family that includes takeout of Drosophila melanogaster. Molecular phylogenetic analysis revealed that the Phormia Takeout-like protein is most similar to the protein encoded by a member of the Drosophila takeout gene family, CG14661, whose expression and function have not been identified yet. Western blot analyses revealed that Phormia Takeout-like protein was exclusively expressed in antennae and labellum of the adult blowfly in both sexes. Immunohistochemical experiments demonstrated that Takeout-like protein was localized around the lamella structure of the auxiliary cells and in the sensillar lymph of the labellar taste sensillum. In antennae, Takeout-like protein was distributed at the base of the olfactory sensilla as well. No significant differences in Takeout-like protein expression were found between the sexes. Our results suggest that Phormia Takeout-like protein is involved in some early events concerned with chemoreception in both the taste and olfactory systems. [source] The presence of phosphate at a catalytic site suppresses the formation of the MgADP-inhibited form of F1 -ATPaseFEBS JOURNAL, Issue 1 2002Noriyo Mitome F1 -ATPase is inactivated by entrapment of MgADP in catalytic sites and reactivated by MgATP or Pi. Here, using a mutant ,3,3, complex of thermophilic F1 -ATPase (,W463F/,Y341W) and monitoring nucleotide binding by fluorescence quenching of an introduced tryptophan, we found that Pi interfered with the binding of MgATP to F1 -ATPase, but binding of MgADP was interfered with to a lesser extent. Hydrolysis of MgATP by F1 -ATPase during the experiments did not obscure the interpretation because another mutant, which was able to bind nucleotide but not hydrolyse ATP (,W463F/,E190Q/,Y341W), also gave the same results. The half-maximal concentrations of Pi that suppressed the MgADP-inhibited form and interfered with MgATP binding were both ,,20 mm. It is likely that the presence of Pi at a catalytic site shifts the equilibrium from the MgADP-inhibited form to the enzyme,MgADP,Pi complex, an active intermediate in the catalytic cycle. [source] Acceleration of granulocyte colony-stimulating factor-induced neutrophilic nuclear lobulation by overexpression of Lyn tyrosine kinaseFEBS JOURNAL, Issue 1 2002Tomomi Omura Stimulation with granulocyte colony-stimulating factor (G-CSF) induces myeloid precursor cells to differentiate into neutrophils, and tyrosine phosphorylation of certain cellular proteins is crucial to this process. However, the signaling pathways for neutrophil differentiation are still obscure. As the Src-like tyrosine kinase, Lyn, has been reported to play a role in G-CSF-induced proliferation in avian lymphoid cells, we examined its involvement in G-CSF-induced signal transduction in mammalian cells. Expression plasmids for wild-type Lyn (Lyn) and kinase-negative Lyn (LynKN) were introduced into a murine granulocyte precursor cell line, GM-I62M, that can respond to G-CSF with neutrophil differentiation, and cell lines that overexpressed these molecules (GM-Lyn, GM-LynKN) were established. Upon G-CSF stimulation, both the GM-Lyn and GM-LynKN cells began to differentiate into neutrophils, showing early morphological changes within a few days, much more rapidly than did the parental cells, which started to exhibit nuclear lobulation about 10 days after the cells were transferred to G-CSF-containing medium. However, the time course of expression of the myeloperoxidase gene, another neutrophil differentiation marker, was not affected by the overexpression of Lyn or LynKN. Therefore, in normal cells, protein interactions with Lyn, but not its kinase activity, are important for the induction of G-CSF-induced neutrophilic nuclear lobulation in mammalian granulopoiesis. [source] Novel domains of the prokaryotic two-component signal transduction systemsFEMS MICROBIOLOGY LETTERS, Issue 1 2001Michael Y. Galperin Abstract The archetypal two-component signal transduction systems include a sensor histidine kinase and a response regulator, which consists of a receiver CheY-like domain and a DNA-binding domain. Sequence analysis of the sensor kinases and response regulators encoded in complete bacterial and archaeal genomes revealed complex domain architectures for many of them and allowed the identification of several novel conserved domains, such as PAS, GAF, HAMP, GGDEF, EAL, and HD-GYP. All of these domains are widely represented in bacteria, including 19 copies of the GGDEF domain and 17 copies of the EAL domain encoded in the Escherichia coli genome. In contrast, these novel signaling domains are much less abundant in bacterial parasites and in archaea, with none at all found in some archaeal species. This skewed phyletic distribution suggests that the newly discovered complexity of signal transduction systems emerged early in the evolution of bacteria, with subsequent massive loss in parasites and some horizontal dissemination among archaea. Only a few proteins containing these domains have been studied experimentally, and their exact biochemical functions remain obscure; they may include transformations of novel signal molecules, such as the recently identified cyclic diguanylate. Recent experimental data provide the first direct evidence of the participation of these domains in signal transduction pathways, including regulation of virulence genes and extracellular enzyme production in the human pathogens Bordetella pertussis and Borrelia burgdorferi and the plant pathogen Xanthomonas campestris. Gene-neighborhood analysis of these new domains suggests their participation in a variety of processes, from mercury and phage resistance to maintenance of virulence plasmids. It appears that the real picture of the complexity of phosphorelay signal transduction in prokaryotes is only beginning to unfold. [source] A microarray model system identifies potential new target genes of the proto-oncogene HOX11GENES, CHROMOSOMES AND CANCER, Issue 4 2004Katrin Hoffmann HOX11 is a homeobox gene originally identified at a chromosomal breakpoint in T-cell acute lymphoblastic leukemia (T-ALL). It is one of the most frequently deregulated genes in T-ALL, although the precise role of HOX11 in leukemogenesis as well as in normal development remains obscure. To gain more insight into the functional role of HOX11, we utilized a microarray model system to characterize the gene expression network that it directs. Using one of our T-ALL cell lines that had been stably transfected to express HOX11 and high-density oligonucleotide HG-U95A arrays, we identified a large number of differentially expressed genes in response to the enforced expression of HOX11. We focused on examining genes found to be up-regulated according to the microarray analysis and selected three putative target genes, NFKB2, SMARCD3, and NR4A3, for further investigation. We could not only confirm the up-regulation of NR4A3 by an independent method in all clones expressing HOX11, but luciferase reporter assays demonstrated that the effect that HOX11 exerted on the proximal promoter of NR4A3 was dependent on the presence of an intact homeodomain, providing support for the idea that HOX11 manifests its regulatory function via its action as a transcription factor. © 2004 Wiley-Liss, Inc. [source] Improved imaging with phase-weighted common conversion point stacks of receiver functionsGEOPHYSICAL JOURNAL INTERNATIONAL, Issue 1 2010A. Frassetto SUMMARY Broad-band array studies frequently stack receiver functions to improve their signal-to-noise ratio while mapping structures in the crust and upper mantle. Noise may produce spurious secondary arrivals that obscure or mimic arrivals produced by P -to- S conversions at large contrasts in seismic impedance such as the Moho. We use a Hilbert transform to calculate phase-weights, which minimize the constructive stacking of erroneous signal in receiver function data sets. We outline this approach and demonstrate its application through synthetic data combined with different types of noise, a previously published example of signal-generated noise, and a large data set from the Sierra Nevada EarthScope Project. These examples show that phase-weighting reduces the presence of signal-generated noise in receiver functions and improves stacked data sets. [source] A Unique Microcracking Process Associated with the Inelastic Deformation of Haversian BoneADVANCED FUNCTIONAL MATERIALS, Issue 1 2009Vincent Ebacher Abstract Since the discovery of the Haversian system in human bone over three hundred years ago, researchers have been wondering about its mechanical advantages. Despite positive experimental evidences on the intervention of Haversian systems in the fracture process, the contributions of Haversian systems to bone fracture have been obscure. Here a unique microcracking process accompanying the inelastic deformation of Haversian bone is reported that may shine light on its structural advantages over other bones. When compressed transversely, the concentric bone lamellae surrounding each Haversian canal allow multiple radial microcracks and arc-shaped cracks to develop intralamellarly. Groups of circumferential arc-shaped microcracks develop in high shear zones and radiate out in oblique directions from each Haversian canal. At the cortical bone level, where the Haversian systems are randomly distributed within the interstitial matrix, multiple nucleations and stable development of such arc-shaped cracks happen to most Haversian systems progressively. As a result, Haversian bone is not sensitive to the presence of Haversian canals and demonstrates high inelastic strains at macroscopic level. [source] | |||||||||||||||||||||||||||||||||||||||||||