bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth, sexual and bone development in a boy with bilateral anorchia under testosterone treatment guided by the development of his monozygotic twin
Authors: Vandewalle Sara , Van Caenegem Eva , Craen Margarita , Taes Youri , Kaufman Jean-Marc , T’Sjoen Guy
Published: April 2018

Background:

Sex steroids are essential for sexual maturation, linear growth and bone development. However, there is no consensus on the optimal timing, dosage and dosage interval of testosterone therapy to induce pubertal development and achieve a normal adult height and bone mass in children with hypogonadism.

Case presentation:

A monozygotic monochorial male twin pair, of which one boy was diagnosed with anorchia at birth due to testicular regression syndrome was followed from the age of 3 until the age of 18 years. Low dose testosterone substitution (testosterone esters 25 mg/2 weeks) was initiated in the affected twin based on the start of pubertal development in the healthy twin and then gradually increased accordingly. Both boys were followed until age 18 and were compared as regards to linear growth, sexual maturation, bone maturation and bone development. Before puberty induction both boys had a similar weight and height. During puberty, a slightly faster weight and height gain was observed in the affected twin. Both boys ended up however, with a similar and normal (near) adult height and weight and experienced a normal development of secondary sex characteristics. At the age of 17 and 18 years, bone mineral density, body composition and volumetric bone parameters at the forearm and calf were evaluated in both boys. The affected boy had a higher lean mass and muscle cross-sectional area. The bone mineral density at the lumbar spine and whole body was similar. Trabecular and cortical volumetric bone parameters were comparable. At one cortical site (proximal radius), however, the affected twin had a smaller periosteal and endosteal circumference with a thicker cortex.

Conclusions:

In conclusion, a low dose testosterone substitution in bilateral anorchia led to a normal onset of pubertal development and (near) adult height. Furthermore, there was no difference in bone mineral density at the age of 17 and 18 years.
Burnout among anesthetists and intensive care physicians
Authors: Mikalauskas Audrius , Benetis Rimantas , Širvinskas Edmundas , Andrejaitienė Judita , Kinduris Šarūnas , Macas Andrius , Padaiga Žilvinas
Published: April 2018

Burnout is a syndrome of depersonalization, emotional exhaustion, and low personal accomplishment. Little is known about burnout in physicians. Our objective was to determine the prevalence of burnout among anesthetists and intensive care physicians, and associations between burnout and personal, as well as professional, characteristics.

Methods

In total, 220 anesthetists and intensive care physicians were contacted by email, asking them to participate in the study. For depression screening the PHQ-2 questionnaire, for problem drinking, CAGE items were used. Burnout was measured by the Maslach Burnout Inventory.

Results

Overall, 34% anesthetists and intensive care physicians indicated high levels of emotional exhaustion, 25% indicated high levels of depersonalization, and 38% showed low personal accomplishment. Burnout was found more frequent among subjects with problem drinking (OR 3.2, 95% CI 1.5–6.8), depressiveness (OR 10.2, 95% CI 4.6–22.6), cardiovascular disorders (OR 3.4, 95% CI 1.7-7.1), and digestive disorders (OR 2.2, 95% CI 1.2–4.0). Some favorite after-work activities positively correlated with burnout, such as sedative medications abuse (OR 4.8, 95% CI 1.8–12.5), alcohol abuse (OR 2.4, 95% CI 1.3–4.5), eating more than usual (OR 1.9, 95% CI 1.1–3.5), and transferring the accumulated stress to relatives (OR 2.8, 95% CI 1.4-5.5). In contrast, reading of non-medical literature seemed to have a protective effect (OR 0.5, 95% CI 0.2–0.9).

Conclusions

Burnout was highly prevalent among anesthetists and intensive care physicians with two fifths of them meeting diagnostic criteria. It was strongly correlated with problem drinking, depressiveness, cardiovascular and digestive disorders, use of sedatives and overeating.
Therapeutische Kommunikation im Kontext von Sportorganisationen: Zur Soziologie depressiver Erkrankungen im Spitzensport
Authors: Kühnle Felix
Published: April 2018

Zur therapeutischen Versorgung depressiver Athleten kooperieren die Vereine und Verbände im Spitzensport häufig mit Psychotherapeuten. Der vorliegende Beitrag analysiert die komplexen Sinnvorgaben therapeutischer Kommunikation zur Behandlung depressiver Spitzensportler mit Hilfe der neueren soziologischen Systemtheorie. Die freiwerdenden Erkenntnisse werden unter besonderer Berücksichtigung der spezifischen Kontextbedingungen in Sportorganisationen reflektiert. Aus Sicht der Sportvereine und -verbände erweist sich die psychotherapeutische Intervention bisweilen als ambivalenter Problemlösungsversuch: Indem Psychotherapeuten systemfremde Logiken einbringen und mit inkongruenten Perspektiven arbeiten, um den Leidensdruck des betroffenen Athleten zu beheben, können sie aufseiten der Organisation durchaus Irritationen stiften und neue Probleme erzeugen.
Ganztagsschulen und Sportvereine als außerschulische Partner: Auf der Suche nach organisationstheoretischen Zugängen
Authors: Thieme Lutz
Published: April 2018

Anhand empirischer Daten zum organisationalem Verhalten von Ganztagsschulen und Sportvereinen wird der Frage nachgegangen, welche allgemeine Organisationstheorie Ansätze zur Erklärung von Kooperationen zwischen Ganztagsschulen und Sportvereinen bereitstellen kann. Nach der kriteriengestützten Identifikation erkenntnisträchtiger Organisationstheorien erfolgt eine explorative hypothesengeleitete empirische Prüfung der Transaktionskostentheorie, der Evolutionstheorie sowie der Theorie der Strukturation mit Längsschnittdaten aus Rheinland-Pfalz. Es zeigt sich, dass der Transaktionskostenansatz das Kooperationsverhalten von Sportvereinen, jedoch nicht von Ganztagsschulen, erklären kann. Die Evolutionstheorie leistet Beiträge zur Erklärung von Stabilität in der Population der Ganztagsschulen sowie zum Wandel bei einem Teil der Kooperationspartner. Das Kooperationsverhalten von Ganztagsschulen kann damit ebenso wie mit der Theorie der Strukturation nicht theoriekonform interpretiert werden.
Digging into the Elusive Localised Solutions of (2+1) Dimensional sine-Gordon Equation
Authors: Radha R. , Senthil Kumar C.
Published: April 2018

In this paper, we revisit the (2+1) dimensional sine-Gordon equation analysed earlier [R. Radha and M. Lakshmanan, J. Phys. A Math. Gen. 29, 1551 (1996)] employing the Truncated Painlevé Approach. We then generate the solutions in terms of lower dimensional arbitrary functions of space and time. By suitably harnessing the arbitrary functions present in the closed form of the solution, we have constructed dromion solutions and studied their collisional dynamics. We have also constructed dromion pairs and shown that the dynamics of the dromion pairs can be turned ON or OFF desirably. In addition, we have also shown that the orientation of the dromion pairs can be changed. Apart from the above classes of solutions, we have also generated compactons, rogue waves and lumps and studied their dynamics.
Effect of sulfur on the scintillation properties of mixed ZnSxSe1–x crystals
Authors: Trubaieva O. G. , Chaika M. A. , Zelenskaya O. V. , Lalayants A. I. , Galkin S. N.
Published: April 2018

ZnSxSe1–x based luminescent materials are promising for use as X-ray and g-ray detectors. The main advantage of ZnSxSe1–x crystals is the possibility of making of solid solutions over an entire X-range. It was found that varying the composition of ZnSxSe1–x crystals can change their luminescent properties. Many studies were focused on obtaining ZnSxSe1–x mixed crystals, most using a vapour phase growth methods, and only some of works used the directional solidification. The directional solidification techniques allow growing large ZnSxSe1–x crystals for high-energy particles detectors. Practical use, however, requires the knowledge about luminescent properties of ZnSxSe1–x bulk crystals.
This study reports the effect of sulfur content on basic properties of ZnSxSe1–xx bulk crystals grown by Bridgman-Stockbarger method. Six different compounds were studied: ZnS0.07Se0.93, ZnS0.15Se0.85, ZnS0.22Se0.78, ZnS0.28Se0.72, ZnS0.32Se0.68, ZnS0.39Se0.61. The ZnSe(Al) and ZnSe(Te) crystals grown at the similar conditions were used as reference. X-ray luminescence was studied using РЕИС-И (REIS-I) X-ray source (Cu, U = 10—45 kV). КСВУ-23 (KSVU-23) spectrophotometer was used to analyse the emission spectra. The afterglow level h(%) was determined by Smiths Heimann AMS-1 spectrophotometer at excitation by such X-ray and g-ray sources as 123Cs and 241Am (59.5 keV).
Light output is one of the main characteristics of the scintillator, which determines its quality as a detector. The ZnSxSe1-x crystals demonstrated increase in the intensity of X-ray induced luminescence spectra with increasing of sulfur content and reached maximum for ZnS0.22Se0.78 composition. Light output of ZnSxSe1–x bulk crystals are higher than those of ZnSe(Te) and ZnSe(Al) commercial crystals. Moreover, thermal stability of scintillation light output of ZnSxSe1–x bulk crystals are also better than those. This investigation has revealed that basic properties of ZnSxSe1–x based scintillation detectors are better than those of ZnSe(Te) and ZnSe(Al).
Application of resettable elements for electrical protection of solar batteries
Authors: Tonkoshkur A. S. , Ivanchenko A. V. , Nakashydze L. V. , Mazurik S. V.
Published: April 2018

The manifestation and formation of various defects in the process of exploitation in real photovoltaic cells and their compounds as well as their work in the regime of changing non-uniform illumination lead to the so-called series and parallel inconsistencies (differences of electrical characteristics) between separate cells and their groups. This results in local overheating and intensifying of degradation processes.
In some cases temporary disconnection (isolation) of the corresponding elements of the solar batteries is more appropriate in order to increase their service life.
In this work additional devices for insulation of overheating cells (and/or components) of solar batteries such as “PolySwith” resettable fuses are proposed to be used as a perspective solution of such problems. These structures are polymer composites with nanosized carbon fillers. Electrical resistance of such a fuse increases abruptly by several orders of magnitude when certain threshold temperature is reached, and when the temperature decreases the fuse returns to its initial high-conductivity state.
This study investigates the possibilities of using the specified type of fuses for electrical insulation of «overheated» photovoltaic cells. Particular attention is paid to the research of the effect of fuses on the working of the solar batteries in the operating temperature range and their functional applicability in emergency situations associated with overheating. The studies were carried out using a model structure of several series of parallel connected photovoltaic cells and specified fuses. Attention is paid to the influence of such factors as the ambient temperature and the drift of the fuses resistance in the conducting state in the process their multiple switching.
It has been established that such protection elements do not influence the work of solar batteries in operating temperature range and are functionally applicable for the electrical isolation of local regions and components of solar batteries with increased temperature.
Report on the National Eye Institute’s Audacious Goals Initiative: Creating a Cellular Environment for Neuroregeneration
Authors: Burns Marie E. , Stevens Beth
Published: April 2018

The cellular environment of the CNS is non-permissive for growth and regeneration. In the retina, transplantation of stem cells has been limited by inefficient survival and integration into existing circuits. In November 2016, as part of the National Eye Institute’s Audacious Goals Initiative (AGI), a diverse collection of investigators gathered for a workshop devoted to articulating the gaps in knowledge, barriers to progress, and ideas for new approaches to understanding cellular environments within the retina and how these environments may be manipulated. In doing so, the group identified the areas of (1) retinal and optic nerve glia, (2) microglia and inflammation, and the (3) extracellular matrix (ECM) and retinal vasculature as key to advancing our understanding and manipulation of the retinal microenvironments. We summarize here the findings of the workshop for the broader scientific community.
Decline of vasopressin immunoreactivity and mRNA levels in the bed nucleus of the stria terminalis following castration
Authors: Miller MA , DeVries GJ , al-Shamma HA , Dorsa DM
Published: April 2018

Vasopressinergic (VP) neurons in the bed nucleus of the stria terminalis (BNST) of the rat are regulated by gonadal steroids. Gonadectomy causes the projections of the BNST to lose their VP immunoreactivity gradually over a period lasting more than 2 months. Here we have compared the rate of decline of VP mRNA and VP immunoreactivity in the BNST of adult male rats following castration. In experiment 1, the peak number of VP-immunoreactive cells and the level of VP gene expression were compared in sham-operated controls and at 1, 3, or 8 weeks postcastration. The number of VP-immunoreactive cells was not decreased at 1 week postcastration but was significantly reduced (p less than 0.0001) at 3 and 8 weeks postcastration. VP gene expression declined more rapidly, and both the total number of labeled cells (p less than 0.0001) and the average number of grains per cell (p less than 0.01) were significantly reduced by 1 week postcastration. No VP-expressing cells were detectable at 3 or 8 weeks. The difference in the rate of decline in the number of cells labeled by the two techniques following castration did not appear to be due to colchicine pretreatment. In experiment 2, VP mRNA in the BNST was compared in sham- operated controls or at 1, 3, or 7 d postcastration. A significant decrease (p less than 0.01) in the average number of grains per cell was detectable by just 1 d following castration, and the number of labeled cells was significantly reduced (p less than 0.001) by 3 d postcastration.(ABSTRACT TRUNCATED AT 250 WORDS)
Segregation of presynaptic inputs on an identified target neuron in vitro: structural remodeling visualized over time
Authors: Bank M , Schacher S
Published: April 2018

Sensory cells of Aplysia form chemical synapses with the motor cell L7 in culture. Under certain conditions, sensory cells will also form electrical connections with each other. Sites of chemical synaptic interaction between the sensory cells and L7 are located at varicosities along sensory cell processes that overlie the main axons of L7, since these structures have been shown ultrastructurally to contain active zones. Previous studies have suggested that the distribution of sensory cell varicosities can be restricted to exclusive regions of the motor cell by the presence of other sensory cells. We wished to investigate (1) how this segregated pattern is generated over time and (2) whether electrical coupling between sensory cells has an effect on this segregated pattern. Using fluorescent dye injection and low-light video microscopy, we visualized the distribution of varicosities for each of two sensory cells growing on L7. In cases in which sensory cells are not electrically coupled, the varicosities from these two cells are spatially segregated on the target after 4 d in culture but not after 2 d in culture. Examination of the varicosity distribution of the same sensory cells on the second and third day of growth indicated both an increased rate in the elimination of varicosities from previously occupied areas and a restriction of varicosity formation in new areas of the target when a second sensory cell is present. For sensory cells that are electrically coupled, varicosities from these cells were not spatially segregated on the target even after 4 d in culture. These observations in vitro suggest that segregation of synaptic inputs by Aplysia sensory cells, which show little spontaneous activity of action potentials, can emerge over time via a process that includes both the elimination of existing sensory varicosities and the restriction of new varicosity formation. Our results also suggest that electrical connections between presynaptic cells can disrupt the segregation of their varicosities on a target, resulting in significant changes in the developing connectivity.
Identification and developmental expression of a novel low molecular weight neuronal intermediate filament protein expressed in Xenopus laevis
Authors: Charnas LR , Szaro BG , Gainer H
Published: April 2018

Xenopus laevis is a valuable model system for the study of vertebrate neuroembryogenesis. However, very few well-characterized nervous system- specific molecular markers are available for studies in this organism. We screened a X. laevis adult brain cDNA library using a cDNA probe for mouse low molecular weight neurofilament protein (NF-L) in order to identify neuron-specific intermediate filament proteins. Clones for two distinct neuron-specific intermediate filament proteins were isolated and sequenced. One of these encoded for a Xenopus NF-L (XNF-L) and the other for a novel neuron-specific Xenopus intermediate filament protein (XNIF) that was present earlier and more abundantly than XNF-L during development. XNIF contained a central rod domain with multiple sequence features characteristic of IF proteins. The XNF-L was very similar to mouse NF-L, with a 77% sequence identity in the rod domain and the presence of a polyglutamic acid region in the tail domain, characteristic of type IV neurofilament proteins. In contrast, XNIF showed only 60% identity to mouse NF-L in the rod domain and lacked the glutamic acid-rich sequence in the tail domain. XNIF also had a very low (approximately 38%) sequence identity in the head and tail domains as compared to NF-L and other neurofilament proteins (45% identity to the head domain of alpha-internexin). In the adult frog, XNIF mRNA is detected by Northern blots only within the nervous system and by in situ hybridization histochemistry exclusively in neurons, particularly in the medullary reticular system and spinal cord. Antisera raised against the unique tail region of XNIF detected a single distinct 60 kDa band in Western blots of nervous system cytoskeletal preparations, and this XNIF immunoreactivity was concentrated in axons in the PNS and in small perikarya in the dorsal root ganglion. In contrast, NF-L immunoreactivity was principally in the large perikarya in the dorsal root ganglion. In development, XNIF mRNA appears more abundant than XNF- L mRNA in all premetamorphic stages examined. XNIF mRNA is first detectable at stage 24 (26 hr), whereas stable expression of XNF-L is at stage 35/36 (50 hr). XNIF immunoreactivity is detectable within the cement gland, within many neuronal cell bodies and axon tracts within the developing nervous system, and within all cellular layers of the developing retina. The availability of these two distinct neuron- specific intermediate filament proteins, with different temporal and spatial expression patterns, should provide new markers as well as targets for functional perturbation in the developing X. laevis nervous system.
Induction of motor neuron sprouting in vivo by ciliary neurotrophic factor and basic fibroblast growth factor
Authors: Gurney ME , Yamamoto H , Kwon Y
Published: April 2018

Ciliary neurotrophic factor (CNTF) and basic fibroblast growth factor (bFGF) were tested for effects on sprouting by motor neurons innervating the adult mouse gluteus muscle. Factors were delivered by subcutaneous injection directly over the surface of the superior gluteus muscle once daily for 7 d and then end plates and axons were visualized by combined silver and cholinesterase staining. CNTF (500 ng daily) induced sprouting both from end plates and from the subset of nodes of Ranvier that are closest to the end plate. The effect of CNTF was potentiated twofold by coadministration of bFGF at doses of 2-20 ng daily, whereas treatment with bFGF alone failed to induce sprouting from either end plates or nodes of Ranvier. The sprouting stimulus delivered by the factors showed limited penetrance into the muscle and restricted lateral spread from the injection site.
Human rod photoreceptor cGMP-gated channel: amino acid sequence, gene structure, and functional expression
Authors: Dhallan RS , Macke JP , Eddy RL , Shows TB , Reed RR , Yau KW , Nathans J
Published: April 2018

Phototransduction in retinal rods involves a G-protein-mediated signaling cascade that leads to cGMP hydrolysis and the closure of a cGMP-gated channel. This channel has recently been purified from bovine retina and molecularly cloned (Kaupp et al., 1989). We report here the cloning of cDNA and genomic DNA encoding the human rod cGMP-gated channel, based upon its homology to the bovine counterpart. The human mRNA structure differs from the bovine in containing an Alu repetitive element spliced into the 5′ untranslated region. The human cGMP-gated channel gene (CNCG) is located on chromosome 4 and contains at least 10 exons. One large exon encodes the carboxy-terminal two-thirds of the protein, whereas seven small exons encode the amino-terminal one-third of the protein. Alternative splicing removes one of the small exons in a subset of transcripts in the human retina, producing an internal in- frame deletion of 36 codons. When expressed in a human embryonic kidney cell line (293S), the full-length cDNA clone, but not the differentially spliced variant, produced functional ion channels broadly similar to the native channels in vertebrate rods.
Dynamics of terminal arbor formation and target approach of retinotectal axons in living zebrafish embryos: a time-lapse study of single axons
Authors: Kaethner RJ , Stuermer CA
Published: April 2018

In a variety of species, developing retinal axons branch initially more widely in their visual target centers and only gradually restrict their terminal arbors to smaller and defined territories. Retinotectal axons in fish, however, appeared to grow in a directed manner and to arborize only at their retinotopic target sites. To visualize the dynamics of retinal axon growth and arbor formation in fish, time-lapse recordings were made of individual retinal ganglion cell axons in the tectum in live zebrafish embryos. Axons were labeled with the fluorescent carbocyanine dyes Dil or DiO inserted as crystals into defined regions of the retina, viewed with 40x and 100x objectives with an SIT camera, and recorded, with exposure times of 200 msec at 30 or 60 sec intervals, over time periods of up to 13 hr. (1) Growth cones advanced rapidly, but the advance was punctuated by periods of rest. During the rest periods, the growth cones broadened and developed filopodia, but during extension they were more streamlined. (2) Growth cones traveled unerringly into the direction of their retinotopic targets without branching en route. At their target and only there, the axons began to form terminal arborizations, a process that involved the emission and retraction of numerous short side branches. The area that was permanently occupied or touched by transient branches of the terminal arbor--“the exploration field”--was small and almost circular and covered not more than 5.3% of the entire tectal surface area, but represented up to six times the size of the arbor at any one time. These findings are consistent with the idea that retinal axons are guided to their retinotopic target sites by sets of positional markers, with a graded distribution over the axes of the tectum.
Response dynamics and directional properties of nonspiking local interneurons in the cockroach cercal system
Authors: Kondoh Y , Arima T , Okuma J , Hasegawa Y
Published: April 2018

The response properties and directional receptive fields of nonspiking local interneurons in the cercal system of the cockroach are described. Wind-evoked responses were recorded intracellularly, and then analyzed by means of the Wiener kernel method in which a Gaussian white noise signal was used as a stimulus. Cross-correlation between the response and the white noise signal produced first- (linear) and second-order (nonlinear) kernels that were used to define input-output characteristics of the interneurons. Three sets of interneurons were distinguished on the basis of kernel analysis. First, responses in interneurons 101, 107, 111, and 203 were characterized predominantly by a differentiating first-order kernel, which suggests a linear relationship to the stimulus. The amplitude and waveform of the kernel changed with the change in stimulus angle, indicating that these four cells are directionally sensitive. Second, responses in interneurons 102 and 103 were also directionally sensitive but highly nonlinear. The first-order kernel was biphasic, whereas the second-order kernel had an elongated depolarizing peak on the diagonal. The response dynamics were accounted for by a cascade of two filters, a linear band-pass filter and a static nonlinear filter, in which the nonlinearity is a signal compression (or a rectification). Third, responses in interneurons 104 and 201 consist largely of the second-order nonlinear component. The second-order kernel, which had an elongated depolarizing peak or a hyperpolarizing valley on the diagonal, did not show any directional preference. The second-order nonlinearity was dynamic, and could be modeled by a band-pass linear filter-static nonlinearity-low-pass linear filter cascade, where the static nonlinearity is a full-wave rectification. The band-pass filter would simply reflect the mechanical property of cercal hair sensilla, whereas the low-pass filter represents the transfer at synapses between the cercal afferents and the interneurons. The nonlinear response thus explains the difference in the directional sensitivity while the differentiating first-order kernel explains the velocity sensitivity of the interneurons. We show that 101 and 107 respond most preferentially to wind from the left versus right, whereas 102, 103, 111, and 203 respond to wind from the front versus rear. Thus, it is suggested that there are two subsystems responding maximally to wind displacement along two coordinate directions, one for the longitudinal direction and the other for the transverse direction. On the other hand, the full-wave-rectifier nonlinear interneurons are omnidirectional, and thus suggested to code simply the power of the wind displacement.
Texture perception and afferent coding distorted by cooling the human ulnar nerve
Authors: Phillips JR , Matthews PB
Published: April 2018

The roughness of standardized surfaces (embossed dot arrays or gratings) was compared by scanning them with the little finger of either hand while the ulnar nerve was cooled unilaterally at the elbow; both hands remained warm. Across-hand comparison of roughness showed that a given surface felt smoother on the cooled side. When the surfaces were adjusted to feel equally rough, that on the cooled side would normally have felt appreciably rougher. The effect of the nerve cooling on axonal conduction was monitored during the psychophysical experiments by stimulating the ulnar nerve above the cooled region and recording the EMG of an ulnar-innervated hand muscle. During cooling, large myelinated axons remained unblocked, but prolongation of their absolute refractory period to 5–10 msec left them unable to transmit trains of impulses at high frequencies (Wedensky inhibition). By varying the length of nerve cooled and the cooling temperature, it was shown that the perceptual effects were not due to an increase in the normal temporal dispersion of impulses transmitted by different-sized afferents. The effect of increasing the absolute refractory period on the signals from the various types of cutaneous afferent was modeled mathematically, using earlier human single-fiber responses to dot arrays. It is concluded that the reduction of perceived roughness with nerve cooling is due to Wedensky inhibition, and that the percept of roughness is related to the local contrast in the afferent spatiotemporal image.
Induced cell death in a thalamic nucleus during a restricted period of zebra finch vocal development
Authors: Johnson F , Bottjer SW
Published: April 2018

A discrete network of forebrain nuclei underlies vocal learning and production in male zebra finches. Three nuclei within this network form a neural pathway that is particularly important for vocal learning in juveniles: area X of the avian striatum projects to the medial dorsolateral nucleus of the anterior thalamus (DLM), which in turn projects to the lateral magnocellular nucleus of the anterior neostriatum (IMAN). Lesions of any of these nuclei in juvenile birds disrupt normal vocal development, whereas the same lesions in adult birds have no effect on already-learned song. Because numerous studies have shown that neuronal survival in the developing nervous system depends on access to efferent targets, we have investigated the possibility that the survival of DLM neurons is similarly regulated over the course of vocal learning. Thus, the efferent target of DLM (IMAN) was lesioned electrolytically in male birds at various stages of vocal development (20, 40, 60 d of age and adult) and birds were killed either 2, 4, or 6 d postlesion. Electrolytic lesions of IMAN removed the single identified efferent target of DLM projection neurons and axotomized the terminal arborizations of these neurons. Although DLM does not normally lose neurons during vocal development, IMAN lesions in 20-d-old birds yielded numerous pyknotic cells throughout DLM by 4 d postlesion and a two-thirds reduction in DLM neuron density by 6 d postlesion. In contrast, IMAN lesions in adult birds had little or no effect on neuronal survival in DLM. Analysis of 40-d-old birds revealed significant but less substantial cell loss than in 20-d-old birds, whereas 60-d-old birds were not different from adults. The age-related decline in the vulnerability of DLM cells to IMAN lesion-induced death suggests that factors that regulate DLM neuron survival may also be involved in the acquisition of learned vocal behavior in songbirds.
Detection of NGF-like activity in human brain tissue: increased levels in Alzheimer's disease
Authors: Crutcher KA , Scott SA , Liang S , Everson WV , Weingartner J
Published: April 2018

A two-site ELISA and a bioassay were used to detect NGF-like activity in human brain tissue. Both assays detected mouse NGF and recombinant human NGF with approximately equal sensitivity, whereas the antibodies showed little cross-reactivity with the recombinant human proteins NT-3 and brain-derived neurotrophic factor. NGF-like activity was detected in fresh human cortical samples obtained from epileptic patients, with the highest activity observed in the right hemisphere of men. NGF-like activity was subsequently measured in autopsy samples of frontal and occipital cortex from patients with Alzheimer's disease (AD) and from individuals with no history or pathological evidence of AD. Based on both the ELISA and the bioassay measurements, NGF-like activity was significantly elevated in both brain regions in AD. These results demonstrate the feasibility of detecting NGF-like activity in both fresh and postmortem human brain tissue and further suggest that AD is characterized by increased, rather than decreased, levels of cortical beta-NGF. The AD-related increase in NGF may be a consequence of degenerative changes in the basal forebrain cholinergic system.
Mutually exclusive expression of alternatively spliced FMRFamide transcripts in identified neuronal systems of the snail Lymnaea
Authors: Bright K , Kellett E , Saunders SE , Brierley M , Burke JF , Benjamin PR
Published: April 2018

The FMRFamide gene of the snail Lymnaea encodes tetrapeptides (FMRFamide/FLRFamide) and heptapeptides (GDPFLRFamide/SDPFLRFamide) on separate exons. In situ hybridization probes specific to these exons were used to map the expression of the two exons in identified neuronal systems of the CNS. Analysis of more than 200 preparations showed that cytoplasmic expression of mRNA was exclusively of one type, with individual neurons expressing either the tetrapeptide or heptapeptide exon. Of the approximately 340 neurons expressing the two exons, the majority (80%) expressed the tetrapeptide exon. The tetrapeptide exon was more widespread, occurring in neurons from all 11 ganglia of the CNS. The heptapeptide was mainly confined to two ganglia (visceral and right parietal), with a small number of cells in three other ganglia. Mapping studies combined with dye marking of identified neurons showed the presence of the tetrapeptide exon in several behaviorally important networks: heart motoneurons, whole body withdrawal response motoneurons, and probably penis motoneurons as well as giant identified neurons (LP1, RPD1). The heptapeptides were prominent in two main clusters of cells (Bgp and Fgp) together with a smaller number of tetrapeptide-expressing cells.
Correlation between insulin-like growth factor (IGF)-binding protein 5 and IGF-I gene expression during brain development
Authors: Bondy C , Lee WH
Published: April 2018

Insulin-like growth factor (IGF)-binding proteins (IGFBPs) potently modulate the interactions of IGF-I and -II with the IGF-I receptor. Previous studies have shown that IGFBP2 gene expression is localized in astroglia, where it is anatomically and temporally coordinated with neuronal IGF-I expression during postnatal brain development. The present study shows that IGFBP5 gene expression is also highly abundant during brain development and also demonstrates significant spatiotemporal correlation with IGF-I, but exhibits a neuroanatomical distribution that is entirely distinct from IGFBP2. IGFBP5 and IGF-I mRNAs are synchronously coexpressed in principal neurons of sensory relay systems, including the olfactory bulb, medial and dorsal lateral geniculate bodies, and ventral tier, cochlear, lemniscal, and vestibular nuclei. They are also transiently coexpressed in principal neurons of the anterodorsal nucleus, but IGF-I mRNA disappears from this structure shortly after birth, while IGFBP5 mRNA remains highly abundant here in the adult. IGFBP5 and IGF-I gene expression demonstrate a temporally coordinated laminar association in the developing cerebellar cortex and hippocampal formation. IGF-I mRNA is concentrated in Purkinje cells, while IGFBP5 mRNA is localized in the external germinal zone in the developing cerebellar cortex. IGFBP5 mRNA is transiently expressed in the retrosplenial and cingulate cortex, subiculum, Ammon's horn, and amygdala, while IGF-I mRNA is contemporaneously localized in large interneurons distributed throughout the hippocampal formation. IGFBP5 mRNA is localized in the lateral ventricular germinal zone at birth and remains in the subventricular zone into maturity. It is also detected in forebrain white matter tracts and olfactory nerve from the second week after birth into maturity. Thus IGFBP5, in addition to IGFBP2, may be a significant determinant of IGF action in the brain. Colocalization in some sites and paralocalization with IGF-I in other sites suggests the potential for autocrine and paracrine interaction between the binding protein and IGF-I in different settings. Arguments are advanced suggesting a role for IGFBPs in the targeting of IGF action to specific cell addresses during brain development.
Intraseptal galanin potentiates scopolamine impairment of delayed nonmatching to sample
Authors: Robinson JK , Crawley JN
Published: April 2018

Galanin coexists with ACh in the basal forebrain and medial septal region. The present study investigated the interactions of the muscarinic receptor antagonist scopolamine and the neuropeptide galanin on an operant spatial delayed non-matching to sample task (DNMTS) in rats. Scopolamine administered both intraperitoneally and microinjected into the medial septum impaired performance on DNMTS. Galanin administered alone into the medial septum did not disrupt DNMTS, but potentiated the disruptive effects of intraperitoneal administered scopolamine. These findings raise the possibility that endogenous galanin may exacerbate cognitive impairments associated with forebrain cholinergic deficits.
Developmental variation in the structure of the retina
Authors: Masland RH , Rizzo JF , Sandell JH
Published: April 2018

Events traditionally called “developmental errors” are known to occur in both vertebrate and invertebrate nervous systems. This study was concerned with the frequency and mode of generation of such events in the mammalian retina. We studied three anomalous structures observed in the rabbit's retina after staining of the cell populations that accumulate indoleamines: type 3 cells, stray processes in the optic fiber layer, and displaced cells. They were counted in rabbit retinas prepared as whole-mounts, and in most cases topological maps were made. For comparison, the conventional indoleamine-accumulating amacrine cells and the tyrosine hydroxylase (TH)-positive cells, which are members of the mammalian retina's recognized complement of amacrine cells, were also counted. A further comparison was made with the number and distribution of TH-positive amacrine cells in highly inbred mice. The ordinary amacrine cells did not vary much in number from animal to animal. Especially in inbred mice, the reproducibility was striking: the extreme variation in number of TH amacrine cells between any two of the 14 retinas studied was 22%, and the mean difference between two eyes of individual mice was 2.5 +/- 1.7%. The three anomalous structures were rare and variable. Their numbers varied more than fourfold from animal to animal. However, their numbers in two eyes from the same animal varied by an overall average of only 14 +/- 10%. The anomalous structures were present in all rabbits, and their morphology was the same in all cases: they are under precise control by the developmental program. The anomalous cells share many phenotypic features with the regular amacrine cells of the indoleamine- accumulating class.(ABSTRACT TRUNCATED AT 250 WORDS)
Regulation of dopamine production by genetically modified primary fibroblasts
Authors: Kang UJ , Fisher LJ , Joh TH , O'Malley KL , Gage FH
Published: April 2018

Primary skin fibroblasts were genetically modified with catecholamine- synthesizing enzyme genes and studied as potential syngeneic donor cells to supply catecholamines in animal models of Parkinson's disease. Primary skin fibroblasts obtained from inbred Fischer 344 rats were transduced with tyrosine hydroxylase (TH) or aromatic L-amino acid decarboxylase (AADC) cDNAs using retroviral vector system. The transduced cells were characterized in vitro by enzymatic assay, immunocytochemistry, and HPLC analysis of catecholamine production and release. Accumulation of high levels of dopamine was detected in the media in a time-dependent manner. Secretion of dopamine and its metabolites appeared to be constitutive without significant storage capacity in vesicles or regulation at the level of secretion. The feasibility of regulating the final dopamine production by the AADC- transduced cells was explored in two ways. First, administration of various doses of the precursor, L-dopa, resulted in a controlled production of dopamine by these cells. Second, coculturing AADC- transduced cells with TH-transduced cells in various proportions allowed control of dopamine production. TH-transduced cells served as an endogenous source of precursor. We propose the use of these cells to study the role of AADC in restoring the dopamine-deficient behavior and to compare the effect of dopamine-producing cells with L-dopa-producing cells either by cografting TH-transduced cells with AADC-transduced cells or by grafting TH-transduced cells alone. The role of AADC in vivo will be assessed in future experiments involving animal models of Parkinson's disease.
Development of orientation selectivity in ferret visual cortex and effects of deprivation
Authors: Chapman B , Stryker MP
Published: April 2018

The orientation selectivity of cells in ferret primary visual cortex was studied during normal development and in animals deprived of vision or of visual cortical activity. In normal animals from the age when visual responses were first recorded (postnatal day 23) through postnatal week 5, only about 25% of cells showed orientation-selective responses. By postnatal week 7, cortical responses had matured to an adult-like state, with approximately 75% of cells clearly selective for orientation. This development of orientation selectivity was not merely a reflection of the development of cortical cell responsiveness: at all ages studied, there was no correlation between responsiveness and selectivity. Infusion of TTX into visual cortex to silence neuronal activity completely blocked the maturation of orientation selectivity. Visual deprivation by bilateral lid suture impaired but did not completely block the normal development of orientation selectivity. We conclude that the maturation of orientation-selective responses in ferret primary visual cortex requires cortical neuronal activity, and that normal development requires visually driven activity.
Developmental changes produced in the retinofugal pathways of rats and ferrets by early monocular enucleations: the effects of age and the differences between normal and albino animals
Authors: Chan SO , Guillery RW
Published: April 2018

Early monocular enucleations were done in rats, either at embryonic day 16 (E16) or on the day of birth, and the surviving uncrossed pathway was studied either at birth for some of the animals enucleated prenatally, or in the adult for all of the other animals. The uncrossed pathways were studied by using HRP as a retrograde tracer. The neonatal enucleations showed the increase of the surviving uncrossed component previously documented by others. In contrast to this, a prenatal enucleation produced a significant reduction in the surviving uncrossed pathway at birth. If these animals survived to be adults, then the surviving uncrossed pathway was slightly increased relative to normal. We conclude that two quite distinct mechanisms have been exposed by these experiments, one acting prenatally and producing a reduction in the uncrossed pathway, and the other acting postnatally and producing an increase. The postnatal effect, which is due to a decrease of the normally occurring ganglion cell death, thus neutralizes the prenatal effect, so that the most effective demonstration of the prenatal effect is to be seen before the period of cell death (early postnatal in rats and ferrets). The same methods were applied to prenatal ferrets at E26- E28 and, in order to see the maximum prenatal effects, the uncrossed pathways were studied at birth in all of these animals. There was a severe reduction of the uncrossed pathway throughout, and this was greatest in the animals with the earliest enucleations. Since the uncrossed pathway in normally reared albino animals is abnormally small, the effects of an early prenatal enucleation in albino rats and ferrets were compared with the effects in normally pigmented animals in order to determine whether the early enucleation was producing an abnormality comparable to the albino abnormality. Prenatal enucleations reduced the uncrossed pathway not only in normally pigmented but also in albino neonatal rats and ferrets. Further, the characteristic position of the nasal border of the temporal retina, which is abnormal in albino animals, was unaffected by the enucleation in either the albino or the pigmented animals, except where, in ferrets, enucleations produced a complete loss of the temporal concentration of ipsilaterally projecting ganglion cells (the temporal crescent). The earlier enucleations showed a greater tendency to produce such a complete loss of the temporal crescent. We conclude that the developmental mechanisms affected by the early enucleations are distinct from those that act to produce the albino abnormality even though both produce an abnormally small uncrossed pathway.(ABSTRACT TRUNCATED AT 400 WORDS)
Presynaptic inhibition of excitatory synaptic transmission mediated by alpha adrenergic receptors in area CA3 of the rat hippocampus in vitro
Authors: Scanziani M , Gahwiler BH , Thompson SM
Published: April 2018

We have investigated the action of norepinephrine (NE) on excitatory synaptic transmission in the hippocampus by recording from CA3 pyramidal cells in organotypic slice cultures. NE (5 microM) was found to decrease the amplitude of pharmacologically isolated EPSPs elicited with stimulation of mossy fibers or recurrent axon collaterals (mean decrease in EPSP amplitude, 44%). Desensitization was observed with repetitive applications. NE did not affect the sensitivity of CA3 cells to iontophoretically applied AMPA, and did not affect the amplitude distribution of TTX-resistant, miniature excitatory synaptic currents. These data suggest that NE acts at presynaptic receptors to decrease glutamate release. This action of NE was blocked by the alpha receptor antagonist phentolamine and the specific alpha 1 receptor antagonist prazosine, but not by the beta receptor antagonist timolol or the alpha 2 receptor antagonist idazoxan. Inhibition of EPSPs by NE was prevented by pretreatment of cultures with pertussis toxin, indicating that G- proteins couple these receptors to their effectors. Stimulation of protein kinase C with phorbol ester blocked the action of NE on EPSPs. This effect, as well as the desensitization of NE responses, was reduced by application of the protein kinase inhibitor staurosporin. Presynaptic inhibition of excitatory synaptic transmission, mediated by alpha adrenergic receptors, represents a novel modulatory action of NE in the hippocampus.
The striopallidal neuron: a main locus for adenosine-dopamine interactions in the brain
Authors: Ferre S , O'Connor WT , Fuxe K , Ungerstedt U
Published: April 2018

Recent pharmacological data suggest that a receptor-receptor interaction between adenosine A2 and dopamine D2 receptors in the brain underlies the behavioral effects of adenosine agonists and adenosine antagonists, such as caffeine and theophylline. According to this interaction, stimulation of A2 receptors inhibits and their blockade potentiates the effects of D2 receptor stimulation. Furthermore, both A2 and D2 receptors are selectively colocalized on GABAergic striopallidal neurons. In this microdialysis investigation the effect of intrastriatal infusion of adenosine and dopamine agonists and antagonists alone or in combination was studied on the release of GABA from the terminals of the striopallidal neuron in awake, freely moving rats. We report that the GABAergic striopallidal neuron, which is a key component of the indirect striatal efferent pathway, is a main locus for A2-D2 interactions in the brain and possibly a main target for the central actions of adenosine agonists and antagonists.
Two stages in visual texture segregation: a lesion study in the cat
Authors: De Weerd P , Sprague JM , Vandenbussche E , Orban GA
Published: April 2018

We have used five cats to investigate the effects of two distinct visual cortex lesions on the segregation of two different texture stimuli. The ablation of areas 17 and 18 (tier I) severely impaired the segregation between textures made of line elements differing in orientation, but spared the segregation between annulus and dot textures. In contrast, the ablation of those areas receiving direct afferents from areas 17 and 18 (tier II) destroyed the segregation for both texture stimuli. Strong deficits remained up to 1 year after the lesion, although limited recovery was observed after tier II lesions. We suggest that tier I areas are involved in the local filtering of the texture elements, and that tier II areas compute texture differences on the basis of the filtered image provided by tier I areas. The crucial contribution to texture segregation of visual areas belonging to a second level in the cortical hierarchy challenges the notion that texture segregation is entirely an early process in vision.