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PubMed1982

Neuronal architecture in nucleus magnocellularis of the chicken auditory system with observations on nucleus laminaris: a light and electron microscope study.

This report presents the major structural features of neurons and their afferent input in nucleus magnocellularis, the avian homologue of the mammalian anteroventral cochlear nucleus. Results of light-microscope observations, as seen in Golgi, Nissl, and normal fiber preparations, as well as ultrastructural morphology are reported. In addition, cells and axons in nucleus laminaris, the presumed homologue of the mammalian medial superior olivary nucleus, are also described. In Golgi-impregnated material, the mature principal cell in nucleus magnocellularis has an ovoid soma encrusted with somatic spines. A dendrite, when present, emerges from the cell soma, travels for a short distance and breaks into a tuft of stubby terminal branches. Foremost among the afferents to nucleus magnocellularis are auditory nerve axons that terminate in large, axosomatic endings, or end-bulbs, covering a large portion of the somatic surface. Other afferents, which also end in relation to the perikaryon, are of undetermined and perhaps multiple origins. The neurons resemble the bushy cells of the mammalian anteroventral cochlear nucleus. Evidence is presented that individual axons from the nucleus magnocellularis bifurcate and send branches to the nucleus laminaris bilaterally, thus placing constraints on the binaural interactions possibly involved in lateralization functions. In electron micrographs, the end-bulbs appear as large, elongate structures which can cover a third of the cell soma. Multiple sites of synaptic specialization occur along these terminals. The synaptic membrane complexes may form directly on the cell body or on the sides or crests of somatic spines. These complexes are characterized by asymmetric membrane densities with a cluster of clear, spherical vesicles on the axonal side. Other small terminal profiles are also present on the somata receiving the end-bulbs. Dendritic profiles are scarce, in agreement with observations in Golgi impregnations. The structural findings indicate that the medial part of the nucleus magnocellularis is homologous to the anterior part of the mammalian anteroventral cochlear nucleus in that the neurons of nucleus magnocellularis are homologous to the bushy cells of the cat. On this basis, the cells in nucleus magnocellularis could faithfully preserve the acoustic response patterns generated in the auditory nerve. This should, in turn, allow a secure relay of bilateral latency differences essential for binaural interactions in the nucleus laminaris.

Animals↗

PubMed1992

Monoamine innervation of bed nucleus of stria terminalis: an electron microscopic investigation.

Immunocytochemical studies showed distinctive monoamine input to the bed nucleus of the stria terminalis (BST). A comparison of axons immunoreactive (IR) for a catecholamine synthetic enzyme [tyrosine hydroxylase (TH) or dopamine beta-hydroxylase (DBH) or phenylethanolamine-N-methyl transferase (PNMT)] or serotonin (5-HT) was performed. TH-IR axons had a greater density in the lateral BST, but DBH-IR and 5-HT-IR axons had a greater density in the medial BST. PNMT-IR axons were dense in the intermediate BST. TH-IR axons had a greater density than DBH- and PNMT-IR axons in the dorsolateral BST, but DBH-IR axons had the greatest density in the ventrolateral BST. Ultrastructural studies revealed that TH-IR terminals formed synapses with soma, dendrites, spines, and axons in the dorsolateral BST. DBH-IR terminals formed synapses with dendritic shafts and spines, and 5-HT-IR terminals formed synapses with dendrites in the ventrolateral BST. Only some 5-HT-IR axons were myelinated. The medial vs. lateral organization of the noradrenergic and dopaminergic afferents in the BST of the rat brain is now evident and is similar to the human brain. The medial-lateral functional subdivision of the BST is supported by the pattern of dopaminergic, noradrenergic, and serotonergic afferents. This demonstration of epinephrine-producing afferents in the BST is the first detailed description of adrenergic input to the BST and aided the determination that catecholaminergic innervation of the ventrolateral BST is predominantly noradrenergic as has been proposed for many years. However, the additional demonstration of rich dopaminergic innervation of the dorsolateral subnucleus suggests further division of the BST into dorsal and ventral functional subgroups.

Animals↗

PubMed1995

Abnormal laterality in schizophrenics and their parents.

Previous studies found that schizophrenics do not show the normal right ear-left hemisphere perceptual advantage on language-related dichotic tests of lateralized cerebral function. We report evidence of a similar abnormality in non-schizophrenic parents of schizophrenic patients. Perceptual asymmetry was first measured with a dichotic word test which had previously yielded differences between schizophrenics and controls. The parents (n = 18) demonstrated a lower right ear advantage (REA) than controls (n = 10) (p = 0.05), but performed similarly to their schizophrenic offspring (n = 10). The same subjects were given two additional tests. Neutral words were paired with words of a positive emotional valence in one test, and with words of a negative emotional valence in the other. On these two tests, the parents were more similar to the controls than to their offspring with the schizophrenics demonstrating a lower REA than their parents (p = 0.005) on the negative test. These results suggest that schizophrenics and their parents have similar abnormalities in hemispheric activation at baseline only, but when listening to words with negative emotional valence, only the schizophrenics demonstrate a further decrease in left hemispheric activation.

Adult↗

PubMed2004

Regioselectivity of taxoid-O-acetyltransferases: heterologous expression and characterization of a new taxadien-5alpha-ol-O-acetyltransferase.

In addition to the anticancer drug Taxol, yew (Taxus) species produce a large variety of other taxane diterpenoids which differ mainly in the type of acyl and aroyl groups appended to the many hydroxyl functions on the taxane core; acetate esters are particularly common. Taxol bears an acetate at C10 and another at C4 thought to originate by intramolecular migration of a C5 acetate function in the process of oxetane ring formation, but many other naturally occurring taxoids bear acetate groups at C1, C2, C7, C9, and C13, in addition to C5 and C10. cDNAs encoding a taxoid 5alpha-O-acetyltransferase (taxadien-5alpha-ol as substrate) and a taxoid 10beta-O-acetyltransferase (10-deacetylbaccatin III as substrate) have been acquired from a recently isolated family of Taxus acyl/aroyltransferase clones. To explore the origins of other acetylated taxoids, the group of recombinant Taxus acyltransferases was investigated with a range of polyhydroxylated taxoids as substrates. From this survey, a new acetyltransferase clone (denoted TAX19) was identified that was capable of acetylating taxadien-5alpha-ol with activity comparable to that of the previously identified 5alpha-O-acetyltransferase (clone TAX1). However, when these two recombinant enzymes were presented with taxadien-triol and tetraol substrates, they exhibited different regiospecificities. The TAX1 enzyme preferentially acetylates the "northern" hemisphere hydroxyls at C9 and C10, whereas the TAX19 enzyme preferentially acetylates the "east-west" pole positions at C5 and C13. The TAX1 enzyme possesses the lowest KM value with taxadien-5alpha-ol (an early pathway metabolite) as substrate, with much higher KM values for the polyhydroxylated taxoid substrates, whereas the TAX19 enzyme possesses lower KM values (than the TAX1 transferase) for all taxoid substrates tested. These results suggest that both TAX1 and TAX19 acyltransferases may function at the early C5 acetylation step of taxoid metabolism, and that the TAX19 acyltransferase, because of its broader specificity for polyhydroxylated taxoids, may also function later in metabolism and be responsible for the production of many other acetylated taxoids.

Acetyl Coenzyme A↗

PubMed2004

Cerebral reserve capacity: implications for alcohol and drug abuse.

Cerebral reserve capacity (or functional reserve) refers to the brain's ability to maintain function when confronted by degenerative processes. Functional reserve can be estimated by several associated measures, including premorbid brain size, premorbid IQ, and level of education attained. There is accumulating evidence that the magnitude of reserve capacity is important in determining the onset and progression of the clinical manifestations of neurodegenerative brain diseases. Normal aging also whittles away at this cerebral reserve, and there may be a consequent unmasking of morbid effects that was not clinically evident when this compensatory reserve was sufficient. We review the evidence supporting this model for a number of degenerative brain processes, including Alzheimer's disease, presenile dementia, HIV dementia, aging, and chronic (multiyear) substance abuse. The concept of cerebral functional reserve has important implications for alcohol and drug abuse morbidity. First, given the high genetic contribution to substance abuse, there is an increased likelihood that the parents of substance abusers were substance abusers themselves. Substance abuse during pregnancy can inhibit brain growth, resulting in reduced brain size and reduced reserve capacity (and therefore less ability to compensate for loss of function later in life). Second, substance abuse is often coupled with poverty, and both substance abuse and poverty are associated with some of the same conditions that reduce brain growth. Finally, we comment on the most important public health implication of the cerebral reserve capacity model (vis-à-vis addiction).

Alcoholism↗

PubMed2006

A tris(2,2'-bipyridyl)cobalt(III)-bovine serum albumin composite membrane for biosensors.

A concept based on a novel redox-biocompatible composite protein membrane fabrication, double enzyme membrane modification technique and antibody immobilization, was exploited to develop a highly sensitive amperometric enzyme immunosensor for detection of carcinoembryonic antigen (CEA). In this concept, a solution of bovine serum albumin (BSA) containing horseradish peroxidase (HRP) is coated on the gold electrode in such a way that the first enzyme membrane is achieved. Then tris(2,2'-bipyridyl) cobalt(III) (Co(bpy)(3)3+), as a mediator, was embedded in BSA-HRP composite membrane vis the electrostatic force and hydrophobe functions. Later a self-assembled conductive nano-Au monolayer was constructed onto the resultant electrode surface by electrostatic interaction between the negatively charged nano-Au and positively charged Co(bpy)3(3+). Protein A is used as a binding material to achieve an adjusted (but not random) orientation of the antibodies surface for efficient combination of antigens. Finally, the HRP, was employed to block the possible remaining active sites and avoid the non-specific adsorption, which acts not only as a blocking reagent instead of the commonly used BSA but also as the conventional enzyme-labeling to amplify the response of the antigen-antibody reaction. The immunosensor constructed with the double layer biocatalytic HRP membranes and the desirable Co(bpy)(3)3+/BSA redox-biocompatible composite membrane performed high sensitivity and a wide linear response to CEA in the range of 0.50-80.00 ng/mL with a limit of detection of 0.14 ng/mL, as well as good stability and long-term life.

Biocompatible Materials↗

PubMed2006

Nutritional antioxidants and age-related cataract and maculopathy.

Loss of vision is the second greatest, next to death, fear among the elderly. Age-related cataract (ARC) and maculopathy (ARM) are two major causes of blindness worldwide. There are several important reasons to study relationships between risk for ARC/ARM and nutrition: (1) because it is likely that the same nutritional practices that are associated with prolonged eye function will also be associated with delayed age-related compromises to other organs, and perhaps, aging in general, (2) surgical resources are insufficient to provide economic and safe surgeries for cataract and do not provide a cure for ARM, and (3) there will be considerable financial savings and improvements in quality of life if health rather than old age is extended, particularly given the rapidly growing elderly segment of our population. It is clear that oxidative stress is associated with compromises to the lens and retina. Recent literature indicates that antioxidants may ameliorate the risk for ARC and ARM. Given the association between oxidative damage and age-related eye debilities, it is not surprising that over 70 studies have attempted to relate antioxidant intake to risk for ARC and ARM. This article will review epidemiological literature about ARC and ARM with emphasis on roles for vitamins C and E and carotenoids. Since glycation and glycoxidation are major molecular insults which involve an oxidative stress component, we also review new literature that relates dietary carbohydrate intake to risk for ARC and ARM. To evaluate dietary effects as a whole, several studies have tried to relate dietary patterns to risk for ARC. We will also give some attention to this emerging research. While data from the observational studies generally support a protective role for antioxidants in foods or supplements, results from intervention trials are less encouraging with respect to limiting risk for ARC/ARM prevalence or progress through antioxidant supplementations, or maintaining higher levels of antioxidants either in diet or blood. Without more information it is difficult to parse these results. It would be worthwhile to determine why the various types of studies are not yielding similar results. However, there are many common insults and mechanistic compromises that are associated with aging, and proper nutrition early in life may address some of these compromises and provide for extended youthful function later in life. Indeed, proper nutrition, possibly including use of antioxidant supplements for the nutritionally impoverished, along with healthy life styles may provide the least costly and most practical means to delay ARC and ARM. Further studies should be devoted to identifying the most effective strategy to prevent or delay the development and progress of ARC/ARM. The efforts should include identifying the right nutrient(s), defining useful levels of the nutrient(s), and determining the age when the supplementation should begin.

Aged↗

PubMed2004

Novel technique for peripheral nerve reconstruction in the absence of an artificial conduit.

The purpose of this study is to promote nerve regeneration across a peripheral nerve gap, using a biologic, tissue-engineered nerve (TEN), containing a high density of viable Schwann cells (SCs) in the absence of supportive foreign materials and a tubular system. Isolated SCs from adult rat sciatic nerve were seeded onto biodegradable constructs and implanted into the backs of nude mice to create TENs. Six weeks later, the constructs were harvested, implanted into surgically created sciatic nerve gaps in rats without supportive artificial conduits and compared with both an autograft group and a silicone conduit group using SCs. Two months later, functional assessment was evaluated by walking track analysis and the implanted lesions were imaged by transmission electron microscopy. The axonal number and sciatic function index of the TEN were significantly higher than those of the silicone group and achieved a comparable level to the autograft group. The results indicate that the large number of SCs within their own extracellular matrix appeared sufficient to enable neuronal growth across a nerve gap in the absence of an artificial conduit and that these circumstances may have a positive effect on the supplement of growth factors from the surrounding tissues of implanted TEN.

Absorbable Implants↗

PubMed2005

The mammalian RNA polymerase II C-terminal domain interacts with RNA to suppress transcription-coupled 3' end formation.

RNA polymerase II plays a critical role not only in transcription of mRNA precursors but also in their subsequent processing. This later function is mediated primarily by the C-terminal domain (CTD) of the enzyme's largest subunit, a unique, repetitive structure conserved throughout eukaryotes and known to interact with a number of different proteins during the transcription cycle. Here, we show that the mammalian CTD also interacts with RNA in a sequence-specific manner. We use a variety of RNA binding assays, including SELEX, to characterize the interaction in vitro and a modified chromatin immunoprecipitation (ChIP) assay to provide evidence that it also occurs in vivo. Transfection assays with the CTD binding consensus situated downstream of a polyadenylation signal indicate that the sequence can suppress mRNA 3' end formation and transcription termination, and in vitro assays indicate that the inhibition of processing is CTD dependent. Our results provide an unexpected function for CTD in modulating gene expression.

3' Untranslated Regions↗

PubMed2005

Enhancement of amphetamine-induced locomotor response in rats on different regimens of diet restriction and 2-deoxy-D-glucose treatment.

Diet restriction (DR) in rodents increases lifespan, reduces age-related disease and pathology, increases stress responses, and maintains better function later into life compared with conventional ad libitum (AL) feeding. We have been investigating different DR regimens and also DR mimetics that stimulate stress response pathways that are activated by DR. By inhibiting glycolysis, feeding or injection of 2-deoxy-D-glucose (2DG) has been proposed as a DR mimetic and has been shown to provide neuroprotection. In the current study, we examined whether 2DG treatment produces behavioral changes similar to those observed in DR rats following stimulation of the dopaminergic (DA) system by D-amphetamine (AMPH). Male Fischer 344 rats were maintained on different dietary regimens: 40% daily DR (40% DR); every-other-day feeding (EOD); or AL with some groups provided food containing 0.4% 2DG or injected i.p. with 2DG. In addition, we examined the persistence of effects of DR or 2DG feeding after switching rats to AL. When locomotor activity was assessed at different time points following initiation of dietary treatments, we noted that the enhancement of AMPH-induced locomotor responses emerged earlier in DR rats than observed in 2DG fed rats, but 40% DR and EOD rats responded in a similar manner. Enhanced locomotor responses persisted in 2DG fed rats even when returned to normal diet for 1 month and in the case of DR rats even after 2 months of AL feeding. Three weeks of 2DG injections also enhanced AMPH response, but this effect was transient. The most important finding was that 2DG did not affect body weight or diet intake yet had effects similar to DR. Thus, 2DG appears to activate DA pathways in the same direction as DR does but without the necessity of reducing caloric intake.

Amphetamine↗

PubMed2005

Canine awake head-out plethysmography (HOP): characterization of external resistive loading and spontaneous laryngeal paralysis.

We applied a novel head-out plethysmographic (HOP) method to study awake canine responses to external resistive loading and natural laryngeal paralysis. Measurements of inspiratory and expiratory specific airway resistance (sRaw(insp), sRaw(exp)) were obtained before and after uni- and bidirectional loading (R(add) = 5 cmH(2)O/L/s) in large-breed dogs (n = 9). Mean sRaw(insp) after inspiratory, and sRaw(exp) after expiratory loading were 31.4 and 33.3 cmH(2)Os, respectively. Bidirectional loads induced a significantly greater rise in both sRaw(insp) and sRaw(exp) (55.1 and 61.3 cmH(2)Os) compared to unidirectional loading (P < 0.001). Yet, type of loading did not affect flow-volume indices. The mean R(aw) of dogs was 4.81 cmH(2)O/L/s. Expiratory loading resulted in a significant 8.8% increase in functional-residual-capacity (FRC), compared to FRC(baseline) (76.7 ml/kg). Dogs (n = 5) with laryngeal paralysis demonstrated a significant increase in sR(aw) and R(aw) compared to controls without changes in FRC. In conclusion, HOP precisely characterized sR(aw) in response to external resistive loading. Hence, we could accurately quantify airway obstruction in awake dogs with laryngeal paralysis.

Airway Resistance↗

PubMed2006

Premorbid IQ as a predictor for the course of IQ in first onset patients with schizophrenia: a 10-year follow-up study.

The aim of the present study was to examine the longitudinal course of IQ and its heterogeneity in patients with schizophrenia, from the perspective of the two main "subtypes" of schizophrenia described in the literature: progressive cognitive deficit versus cognitive stabilisation or recovery. Premorbid IQ scores and WAIS IQ scores of 100 first onset patients were obtained at first hospitalization (T1) and after 10 years (T2). Significant changes in IQ over time were found, representing (i) at T1, a deterioration compared to premorbid intelligence (B=-6.3, 95% CI -9.5 to -3.0, p<0.0001), followed by (ii) a recovery at T2 where IQ matched premorbid intelligence again (B=0.5, 95% CI -3.1 to 4.0, p=0.79). In addition, a significant interaction was found between course of IQ over time and estimated premorbid IQ, demonstrating that subjects with lower premorbid IQ levels remained stable over time whereas in individuals with higher premorbid IQ levels a pattern of deterioration was evident at T1, followed by a recovery up to premorbid level at T2. The data confirm the importance of estimated premorbid IQ as an indicator of the longitudinal course of cognitive functioning in patients with schizophrenia and add evidence to the hypothesis of heterogeneity or "subtypes" of schizophrenia. The data, however, do not confirm the existence of progressive deterioration of cognitive functioning. Rather, catching up of cognitive function later in the course of the illness may take place in those whose deficits become apparent in the early phases of illness, whereas those with the most severe premorbid impairments remain stable.

Adult↗

PubMed2005

Effects of nutritional restrictions during post-hatching development on adrenocortical function in western scrub-jays (Aphelocoma californica).

Altricial birds grow rapidly during post-hatching period and are developmentally sensitive to variations in food supply. Limited food results in elevated corticosterone levels in chicks of semi-precocial birds but it is not clear whether altricial songbirds show similar adrenocortical stress response to nutritional restrictions during early development. It is also unknown how nutritional stress during early development affects the adrenocortical function later in life in altricial birds which show tremendous variation in the magnitude of adrenocortical stress response. Using western scrub-jays (Aphelocoma californica), we experimentally demonstrated that moderate food restrictions (65% of ad libitum) during post-hatching development caused significant elevation of baseline corticosterone levels in nest-bound chicks. Compared to controls, 1-year-old scrub-jays that experienced nutritional deficits during post-hatching development also showed a marginally significant trend to have stronger adrenocortical stress response and significantly greater degree of fluctuating asymmetry in bone and feather measurements. Thus, our results demonstrated that developing altricial birds show adrenocortical response to nutritional deficits, which might produce long-term changes in responsiveness of the adrenal system. Our study suggests that baseline corticosterone levels are a good indicator of physiological conditions of developing birds and that individual variance in adrenocortical stress response commonly observed in many species might, at least in part, be explained by environmental conditions during early development. Considering that nutritional restrictions during early development are linked to many permanent changes including impaired cognitive abilities, corticosterone levels in developing young might be a reliable predictor of their future fitness.

Adrenal Cortex↗

PubMed2003

Mitochondrial intermembrane proteins in cell death.

Apoptosis is a form of programmed cell death important in the development and tissue homeostasis of multicellular organisms. Mitochondria have, next to their function in respiration, an important role in the apoptotic-signaling pathway. Malfunctioning at any level of the cell is eventually translated in the release of apoptogenic factors from the mitochondrial intermembrane space resulting in the organized demise of the cell. Some of these factors, such as AIF and endonuclease G, appear to be highly conserved during evolution. Other factors, like cytochrome c, have gained their apoptogenic function later during evolution. In this review, we focus on the role of cytochrome c, AIF, endonuclease G, Smac/DIABLO, Omi/HtrA2, Acyl-CoA-binding protein, and polypyrimidine tract-binding protein in the initiation and modulation of cell death in different model organisms. These mitochondrial factors may contribute to both caspase-dependent and caspase-independent processes in apoptotic cell death.

Animals↗

PubMed1986

Subcortical transfer of cognitive information in subjects with complete forebrain commissurotomy.

Three complete commissurotomy subjects were tested for the ability to integrate cognitive information presented for a prolonged duration to opposite visual hemi-fields. A sample stimulus was projected to one hemi-field and a three-choice array to the other, with one choice related to the sample on an abstract or concrete basis. All subjects performed the non-verbal matching task at well above chance level, with scores comparable to those attained when the task was performed completely within one or the other hemisphere. Transfer was equally successful in the two directions, though the pathway originating in the right and terminating in the left hemisphere may be more sensitive to affective components of the stimulus. The information relayed subcortically is neither verbal nor imagic in nature, but appears to correspond to contextual or connotative associates of the stimulus. The results are discussed in terms of a cognitive system common to the two hemispheres and involving associational networks but not lateralized functions such as language and complex visuospatial processes.

Adult↗

PubMed1988

Hemispheric specialization for tactile perception opposed by contralateral noise.

The aim of this study was to investigate the contribution of each cerebral hemisphere in the categorization of tactile information with and without contralateral tactile noise. Two groups of subjects rated the dissimilarity of paired stimuli varying in shape and texture presented to the left or right hand, with contralateral noise in the other hand for one group only. Analysis of variance on derived structured indices showed a general left hand advantage in the treatment of this haptic information. Moreover, a group by hand interaction revealed that noise-exposed subjects showed better differentiation of tactile information for stimuli presented to the left hand. The data suggest a unidirectional interference by the left hemisphere in the processing of tactile information in noise-free conditions and that quality of interhemispheric transfer of information may modulate cerebral functional lateralization.

Adult↗

PubMed1998

Structure and function of the parasitophorous vacuole in Eimeria species.

The intracellular life-cycle of Eimeria are located in the host cell within a membrane-bound parasitophorous vacuole. The invasion process and the formation of the parasitophorous vacuole are mediated by characteristic organelles within the apical complex. During invasion, the parasitophorous-vacuole membrane is manipulated by the parasite and functions later in the development cycle as a molecular sieve, allowing the exchange of metabolites between parasite and host cell. Unlike the cyst-forming coccidia, there is little evidence of parasitophorous-vacuole membrane transformation in the later stages of the lifecycle of Eimeria species. Compared with the human pathogens Plasmodium and Toxoplasma, rather little is known about the parasitophorous vacuole and parasitophorous-vacuole membrane of animal pathogens of the genus Eimeria.

Animals↗

PubMed1997

Effects of uni- and bilateral phrenicotomy on active and passive respiratory mechanics in rats.

Eighteen spontaneously breathing anesthetized rats were selected to belong to three groups: control (C), unilateral (U), and bilateral phrenicotomy (B). Eight days after surgery, the passive and active mechanical properties of the respiratory system, the shape of the occlusion pressure wave, the decay of inspiratory muscle activity during expiration and control of breathing were analysed. Passive and active elastances increased significantly from C to U and from U to B. Passive and active time constants decreased either in uni- or bilateral phrenicotomies. Passive and active resistances remained unaltered. The intensity of respiratory drive increased from C to U and B. In conclusion, uni- and bilateral phrenicotomies increase the elastic load of the respiratory system, because of both its passive and active components, which raised the respiratory neuromuscular drive of the remaining muscles. Consequently, minute ventilation remained unchanged. The higher frequency was allowed for, by a shorter time constant of the respiratory system and by a faster decay of post-inspiratory muscle activity.

Air Pressure↗