Commissural Axons of the Mouse Cochlear Nucleus

PubMed Central

Brown, M. Christian; Drottar, Marie; Benson, Thane E.; Darrow, Keith

2012-01-01

The axons of commissural neurons that project from one cochlear nucleus to the other were studied after labeling with anterograde tracer. Injections were made into the dorsal subdivision of the cochlear nucleus in order to restrict labeling only to the group of commissural neurons that gave off collaterals to, or were located in, this subdivision. The number of labeled commissural axons in each injection was correlated with the number of labeled radiate multipolar neurons, suggesting radiate neurons as the predominant origin of the axons. The radiate commissural axons are thick and myelinated, and they exit the dorsal acoustic stria of the injected cochlear nucleus to cross the brainstem in the dorsal half, near the crossing position of the olivocochlear bundle. They enter the opposite cochlear nucleus via the dorsal and ventral acoustic stria and at its medial border. Reconstructions of single axons demonstrate that terminations are mostly in the core and typically within a single subdivision of the cochlear nucleus. Extents of termination range from narrow to broad along both the dorso-ventral (i.e. tonotopic) and rostro-caudal dimensions. In the electron microscope, labeled swellings form synapses that are symmetric (in that there is little postsynaptic density), a characteristic of inhibitory synapses. Our labeled axons do not appear to include excitatory commissural axons that end in edge regions of the nucleus. Radiate commissural axons could mediate the broad-band inhibition observed in responses to contralateral sound, and they may balance input from the two ears on a quick time course. PMID:23124982

Development of an integrative algorithm for the treatment of various stages of full-thickness burns of the first commissure of the hand.

PubMed

Yuste, Valentin; Delgado, Julio; Agullo, Alberto; Sampietro, Jose Mauel

2017-06-01

Burns of the first commissure of the hand can evolve into an adduction contracture of the thumb. We decided to conduct a review of the existing literature on the treatment of full-thickness burns of the first commissure in order to develop a treatment algorithm that integrates the various currently available procedures. A search of the existing literature was conducted, focusing on the treatment of a burn of the first commissure in its chronic and acute phases. A total of 29 relevant articles were selected; 24 focused exclusively on the chronic contracture stage, while 3 focused exclusively on the acute burn stage, and 2 articles studied both stages. A therapeutic algorithm for full-thickness burns of the first commissure of the hand was developed. With this algorithm we sought to relate each degree and stage of the burn with a treatment. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

Locomotor damage in rats after X-irradiation in utero

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mullenix, Phyllis; Norton, Stata; Culver, Bruce

1975-08-01

Alterations in gait were found in rats after whole-body irradiation with 125 R on day 14, 15, and 16 of gestation. No effects on locomotion were detected after irradiation on day 17 with 125 R or after irradiation on day 14 with 50 R. A technique was set up for quantitative evaluation of locomotion based on a modification of other methods. Walking patterns of irradiated rats were recorded, when they were adults, by requiring them to walk up a 10$sup 0$ incline through a corridor after their feet had been dipped in ink. Rats irradiated on gestational day 14 hadmore » an in-phase, hopping gait with the sine of the angle between the hind feet and the direction of progression over 0.9. Rats irradiated on gestational days 15 and 16 had an alternating, waddling gait with wider stance and broader angle than control rats. Histologic examination of serial sections of the brains of these rats showed that the 14-day rats lacked all telencephalic commissures except for a few fibers which crossed in some rats. There was a progressive improvement in the condition of the anterior and ventral hippocampal commissures up to day 17, but the corpus callosum and doral hippocampal commissure were lacking or markedly reduced in all day 17 rats. No animals showed damage to the mesencephalic posterior commissure. Since rats which used the in-phase mode of locomotion were never observed to use alternating gait, the possible causal relationship of the commissural damage to the altered locomotor patterns was considered. In view of the restricted period of damage found for the anterior and ventral hippocampal commissures and the restriction of altered locomotion to damage in the same period, primary involvement of the corpus callosum and dorsal hippocampal commissure could be excluded, but a possible role for the other telencephalic commissures remained. (auth)« less

Sema-1a Reverse Signaling Promotes Midline Crossing in Response to Secreted Semaphorins.

PubMed

Hernandez-Fleming, Melissa; Rohrbach, Ethan W; Bashaw, Greg J

2017-01-03

Commissural axons must cross the midline to form functional midline circuits. In the invertebrate nerve cord and vertebrate spinal cord, midline crossing is mediated in part by Netrin-dependent chemoattraction. Loss of crossing, however, is incomplete in mutants for Netrin or its receptor Frazzled/DCC, suggesting the existence of additional pathways. We identified the transmembrane Semaphorin, Sema-1a, as an important regulator of midline crossing in the Drosophila CNS. We show that in response to the secreted Semaphorins Sema-2a and Sema-2b, Sema-1a functions as a receptor to promote crossing independently of Netrin. In contrast to other examples of reverse signaling where Sema1a triggers repulsion through activation of Rho in response to Plexin binding, in commissural neurons Sema-1a acts independently of Plexins to inhibit Rho to promote attraction to the midline. These findings suggest that Sema-1a reverse signaling can elicit distinct axonal responses depending on differential engagement of distinct ligands and signaling effectors. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Mechanisms of Left-Right Coordination in Mammalian Locomotor Pattern Generation Circuits: A Mathematical Modeling View

PubMed Central

Talpalar, Adolfo E.; Rybak, Ilya A.

2015-01-01

The locomotor gait in limbed animals is defined by the left-right leg coordination and locomotor speed. Coordination between left and right neural activities in the spinal cord controlling left and right legs is provided by commissural interneurons (CINs). Several CIN types have been genetically identified, including the excitatory V3 and excitatory and inhibitory V0 types. Recent studies demonstrated that genetic elimination of all V0 CINs caused switching from a normal left-right alternating activity to a left-right synchronized “hopping” pattern. Furthermore, ablation of only the inhibitory V0 CINs (V0D subtype) resulted in a lack of left-right alternation at low locomotor frequencies and retaining this alternation at high frequencies, whereas selective ablation of the excitatory V0 neurons (V0V subtype) maintained the left–right alternation at low frequencies and switched to a hopping pattern at high frequencies. To analyze these findings, we developed a simplified mathematical model of neural circuits consisting of four pacemaker neurons representing left and right, flexor and extensor rhythm-generating centers interacting via commissural pathways representing V3, V0D, and V0V CINs. The locomotor frequency was controlled by a parameter defining the excitation of neurons and commissural pathways mimicking the effects of N-methyl-D-aspartate on locomotor frequency in isolated rodent spinal cord preparations. The model demonstrated a typical left-right alternating pattern under control conditions, switching to a hopping activity at any frequency after removing both V0 connections, a synchronized pattern at low frequencies with alternation at high frequencies after removing only V0D connections, and an alternating pattern at low frequencies with hopping at high frequencies after removing only V0V connections. We used bifurcation theory and fast-slow decomposition methods to analyze network behavior in the above regimes and transitions between them. The model reproduced, and suggested explanation for, a series of experimental phenomena and generated predictions available for experimental testing. PMID:25970489

Rhythm generation, coordination, and initiation in the vocal pathways of male African clawed frogs

PubMed Central

Cavin Barnes, Jessica; Appleby, Todd

2016-01-01

Central pattern generators (CPGs) in the brain stem are considered to underlie vocalizations in many vertebrate species, but the detailed mechanisms underlying how motor rhythms are generated, coordinated, and initiated remain unclear. We addressed these issues using isolated brain preparations of Xenopus laevis from which fictive vocalizations can be elicited. Advertisement calls of male X. laevis that consist of fast and slow trills are generated by vocal CPGs contained in the brain stem. Brain stem central vocal pathways consist of a premotor nucleus [dorsal tegmental area of medulla (DTAM)] and a laryngeal motor nucleus [a homologue of nucleus ambiguus (n.IX-X)] with extensive reciprocal connections between the nuclei. In addition, DTAM receives descending inputs from the extended amygdala. We found that unilateral transection of the projections between DTAM and n.IX-X eliminated premotor fictive fast trill patterns but did not affect fictive slow trills, suggesting that the fast and slow trill CPGs are distinct; the slow trill CPG is contained in n.IX-X, and the fast trill CPG spans DTAM and n.IX-X. Midline transections that eliminated the anterior, posterior, or both commissures caused no change in the temporal structure of fictive calls, but bilateral synchrony was lost, indicating that the vocal CPGs are contained in the lateral halves of the brain stem and that the commissures synchronize the two oscillators. Furthermore, the elimination of the inputs from extended amygdala to DTAM, in addition to the anterior commissure, resulted in autonomous initiation of fictive fast but not slow trills by each hemibrain stem, indicating that the extended amygdala provides a bilateral signal to initiate fast trills. NEW & NOTEWORTHY Central pattern generators (CPGs) are considered to underlie vocalizations in many vertebrate species, but the detailed mechanisms underlying their functions remain unclear. We addressed this question using an isolated brain preparation of African clawed frogs. We discovered that two vocal phases are mediated by anatomically distinct CPGs, that there are a pair of CPGs contained in the left and right half of the brain stem, and that mechanisms underlying initiation of the two vocal phases are distinct. PMID:27760822

Central projections of the nervus terminalis and the nervus praeopticus in the lungfish brain revealed by nitric oxide synthase.

PubMed

Schober, A; Meyer, D L; Von Bartheld, C S

1994-11-01

Lungfishes possess two cranial nerves that are associated with the olfactory system: the nervus terminalis enters the telencephalon with the olfactory nerve, and the nervus praeopticus enters the diencephalon at the level of the optic nerve. We investigated the central projections of the nervus terminalis and the nervus praeopticus in the Australian lungfish (Neoceratodus forsteri) and in the African lungfish (Protopterus dolloi) by NADPH-diaphorase histochemistry (nitric oxide synthase; NOS) and compared them with the projections of the nervus terminalis of the frog (Xenopus laevis). In Neoceratodus, NOS-positive fascicles of the nervus terminalis divide and project with a ventral component through the septum and with a dorsal component through the pallium; fibers of both trajectories extend caudally beyond the anterior commissure and join the lateral forebrain bundle. In the nervus praeopticus, about 300 fibers contain NOS; they innervate the preoptic nucleus and continue their course through the diencephalon; many fibers cross in the commissure of the posterior tuberculum. In Protopterus, ganglion cells of the nervus terminalis and of the nervus praeopticus contain NOS. NOS-positive fibers of the nervus terminalis project through the septal region but not through the pallium. Several major fascicles cross in the rostral part of the anterior commissure, where they are joined by a small number of NOS-containing fibers of the nervus praeopticus. Both nerves innervate the preoptic nucleus. The number and pathways of the fascicles of the nervus terminalis are not always symmetric between the two sides. The nervus terminalis fascicles remain in a ventral position, whereas the nervus praeopticus gives rise to the more dorsal fascicles. Many fibers of the two nerves extend throughout the diencephalon and cross in the commissure of the posterior tuberculum. These findings demonstrate many similarities but also significant differences between the contributions of the nervus terminalis and the nervus praeopticus to forebrain projections in the two lungfishes. They support the view that the nervus praeopticus is part of a nervus terminalis system comparable to that in frogs and other nonmammalian vertebrates.

Percutaneous Mitral Valve Dilatation: Single Balloon versus Double Balloon - A Finite Element Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schievano, Silvia; Kunzelman, Karyn; Nicosia, Mark

2009-01-01

Background: Percutaneous mitral valve (MV) dilatation is performed with either a single balloon (SB) or double balloon (DB) technique. The aim of this study was to compare the two balloon system results using the finite element (FE) method. Methods and Results: An established FE model of the MV was modified by fusing the MV leaflet edges at commissure level to simulate a stenotic valve (orifice area=180mm2). A FE model of a 30mm SB (low-pressure, elastomeric balloon) and an 18mm DB system (high-pressure, non-elastic balloon) was created. Both SB and DB simulations resulted in splitting of the commissures and subsequent stenosismore » dilatation (final MV area=610mm2 and 560mm2 respectively). Stresses induced by the two balloon systems varied across the valve. At the end of inflation, SB showed higher stresses in the central part of the leaflets and at the commissures compared to DB simulation, which demonstrated a more uniform stress distribution. The higher stresses in the SB analysis were due to the mismatch of the round balloon shape with the oval mitral orifice. The commissural split was not easily accomplished with the SB due to its high compliance. The high pressure applied to the DB guaranteed the commissural split even when high forces were required to break the commissure welds. Conclusions: The FE model demonstrated that MV dilatation can be accomplished by both SB and DB techniques. However, the DB method resulted in higher probability of splitting of the fused commissures and less damage caused to the MV leaflets by overstretching.« less

The paired domain-containing nuclear factor pax[b] is expressed in specific commissural interneurons in zebrafish embryos.

PubMed

Mikkola, I; Fjose, A; Kuwada, J Y; Wilson, S; Guddal, P H; Krauss, S

1992-10-01

The zebrafish paired box (Pax) genes are expressed in the early neural tube and are thought to be transcription factors that regulate the differentiation of cells in the central nervous system (CNS). The protein product of one of these Pax genes, pax[b], is detectable as a nuclear antigen in all the regions of the embryo that transcribe the gene including the posterior midbrain, the nephritic primordium, the Wolffian duct, the optic stalk, and, in specific neurons, in the hindbrain and spinal cord. The timing and pattern of axonal outgrowth by the early pax[b]-positive neurons suggest that they are the commissural secondary ascending (CoSA) interneurons in the spinal cord; the primary commissural interneurons (MiD2c and MiD3c) in hindbrain rhombomeres mi2 and mi3; and a previously unclassified set of commissural interneurons that we termed the commissural caudalrhombomere ascending (CoCaA) interneurons in the caudal hindbrain. In contrast, the Mauthner interneurons do not express pax[b] early in development. Shortly after the appearance of the first pax[b]-positive interneurons, additional nuclei adjacent to the first pax[b]-positive interneurons become pax[b] positive. This pattern of expression suggests that the pax[b] protein may be involved in determining the identity of specific commissural interneurons.

Spatial distribution of intermingling pools of projection neurons with distinct targets: A 3D analysis of the commissural ganglia in Cancer borealis.

PubMed

Follmann, Rosangela; Goldsmith, Christopher John; Stein, Wolfgang

2017-06-01

Projection neurons play a key role in carrying long-distance information between spatially distant areas of the nervous system and in controlling motor circuits. Little is known about how projection neurons with distinct anatomical targets are organized, and few studies have addressed their spatial organization at the level of individual cells. In the paired commissural ganglia (CoGs) of the stomatogastric nervous system of the crab Cancer borealis, projection neurons convey sensory, motor, and modulatory information to several distinct anatomical regions. While the functions of descending projection neurons (dPNs) which control downstream motor circuits in the stomatogastric ganglion are well characterized, their anatomical distribution as well as that of neurons projecting to the labrum, brain, and thoracic ganglion have received less attention. Using cell membrane staining, we investigated the spatial distribution of CoG projection neurons in relation to all CoG neurons. Retrograde tracing revealed that somata associated with different axonal projection pathways were not completely spatially segregated, but had distinct preferences within the ganglion. Identified dPNs had diameters larger than 70% of CoG somata and were restricted to the most medial and anterior 25% of the ganglion. They were contained within a cluster of motor neurons projecting through the same nerve to innervate the labrum, indicating that soma position was independent of function and target area. Rather, our findings suggest that CoG neurons projecting to a variety of locations follow a generalized rule: for all nerve pathway origins, the soma cluster centroids in closest proximity are those whose axons project down that pathway. © 2017 Wiley Periodicals, Inc.

Reconstruction of large defects of the lips and commissure using a composite radial forearm palmaris longus free flap associated with a lengthening temporalis myoplasty.

PubMed

Martin, Thomas; Sury, Florent; Goga, Dominique; Parmentier, Jerome; Rozen, Adam; Laure, Boris

2012-08-01

We performed a single-stage operation to reconstruct a large defect of the lips and commissure using a composite radial forearm-palmaris longus free flap. To obtain cranial traction and a voluntary smile, independently from any jaw movement, traction was achieved by using a lengthening temporalis myoplasty. The tendon attached to the coronoid process was fixed to the palmaris longus tendon, recreating a new commissure and a "neo-modiolus." Physical therapy was started on the 21st postoperative day to facilitate progress from a "mandibular smile," to ideally a spontaneous and symmetric smile after 3 months of therapy. This procedure was able to obtain good oral continence and a good commissural movement during smile which has not previously been mentioned in the published literature.

The horseshoe-shaped commissure of Wernekinck or the decussation of the brachium conjunctivum methodological changes in the 1840s.

PubMed

Voogd, Jan; van Baarsen, Kirsten

2014-02-01

Up till the 1840s, gross dissection was the only method available to study the tracts and fascicles of the white matter of the human brain. This changed dramatically with the introduction by Stilling (1842, 1843, 1846) of the microscopy of serial sections and his demonstration of the discriminative power of this method. The decussation of the brachium conjunctivum (the superior cerebellar peduncle) (International Anatomical Terminology (1998)) originally was known as the horseshoe-shaped commissure of Wernekinck. The first use of this name and the first illustrations of this commissure date from a book by Wernekinck’s successor, Wilbrand (1840).Using gross dissection, he concluded that the commissure connects the dentate nucleus with the contralateral inferior olive. A few years later, Stilling (1846), using microscopy of serial sections through the human brain stem, illustrated the entire course of the brachium conjunctivum, its decussation,and its crossed ascending branch, up to the red nucleus. From his work, it became clear that Wernekinck and Wilbrand had included the central tegmental tract in their commissure, and that they had failed to identify its ascending branch.

Testing the connections within face processing circuitry in Capgras delusion with diffusion imaging tractography

PubMed Central

Bobes, Maria A.; Góngora, Daylin; Valdes, Annette; Santos, Yusniel; Acosta, Yanely; Fernandez Garcia, Yuriem; Lage, Agustin; Valdés-Sosa, Mitchell

2016-01-01

Although Capgras delusion (CD) patients are capable of recognizing familiar faces, they present a delusional belief that some relatives have been replaced by impostors. CD has been explained as a selective disruption of a pathway processing affective values of familiar faces. To test the integrity of connections within face processing circuitry, diffusion tensor imaging was performed in a CD patient and 10 age-matched controls. Voxel-based morphometry indicated gray matter damage in right frontal areas. Tractography was used to examine two important tracts of the face processing circuitry: the inferior fronto-occipital fasciculus (IFOF) and the inferior longitudinal (ILF). The superior longitudinal fasciculus (SLF) and commissural tracts were also assessed. CD patient did not differ from controls in the commissural fibers, or the SLF. Right and left ILF, and right IFOF were also equivalent to those of controls. However, the left IFOF was significantly reduced respect to controls, also showing a significant dissociation with the ILF, which represents a selective impairment in the fiber-tract connecting occipital and frontal areas. This suggests a possible involvement of the IFOF in affective processing of faces in typical observers and in covert recognition in some cases with prosopagnosia. PMID:26909325

Masseteric nerve for reanimation of the smile in short-term facial paralysis.

PubMed

Hontanilla, Bernardo; Marre, Diego; Cabello, Alvaro

2014-02-01

Our aim was to describe our experience with the masseteric nerve in the reanimation of short term facial paralysis. We present our outcomes using a quantitative measurement system and discuss its advantages and disadvantages. Between 2000 and 2012, 23 patients had their facial paralysis reanimated by masseteric-facial coaptation. All patients are presented with complete unilateral paralysis. Their background, the aetiology of the paralysis, and the surgical details were recorded. A retrospective study of movement analysis was made using an automatic optical system (Facial Clima). Commissural excursion and commissural contraction velocity were also recorded. The mean age at reanimation was 43(8) years. The aetiology of the facial paralysis included acoustic neurinoma, fracture of the skull base, schwannoma of the facial nerve, resection of a cholesteatoma, and varicella zoster infection. The mean time duration of facial paralysis was 16(5) months. Follow-up was more than 2 years in all patients except 1 in whom it was 12 months. The mean duration to recovery of tone (as reported by the patient) was 67(11) days. Postoperative commissural excursion was 8(4)mm for the reanimated side and 8(3)mm for the healthy side (p=0.4). Likewise, commissural contraction velocity was 38(10)mm/s for the reanimated side and 43(12)mm/s for the healthy side (p=0.23). Mean percentage of recovery was 92(5)mm for commissural excursion and 79(15)mm/s for commissural contraction velocity. Masseteric nerve transposition is a reliable and reproducible option for the reanimation of short term facial paralysis with reduced donor site morbidity and good symmetry with the opposite healthy side. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Comparison of hemihypoglossal nerve versus masseteric nerve transpositions in the rehabilitation of short-term facial paralysis using the Facial Clima evaluating system.

PubMed

Hontanilla, Bernardo; Marré, Diego

2012-11-01

Masseteric and hypoglossal nerve transfers are reliable alternatives for reanimating short-term facial paralysis. To date, few studies exist in the literature comparing these techniques. This work presents a quantitative comparison of masseter-facial transposition versus hemihypoglossal facial transposition with a nerve graft using the Facial Clima system. Forty-six patients with complete unilateral facial paralysis underwent reanimation with either hemihypoglossal transposition with a nerve graft (group I, n = 25) or direct masseteric-facial coaptation (group II, n = 21). Commissural displacement and commissural contraction velocity were measured using the Facial Clima system. Postoperative intragroup commissural displacement and commissural contraction velocity means of the reanimated versus the normal side were first compared using a paired sample t test. Then, mean percentages of recovery of both parameters were compared between the groups using an independent sample t test. Onset of movement was also compared between the groups. Significant differences of mean commissural displacement and commissural contraction velocity between the reanimated side and the normal side were observed in group I but not in group II. Mean percentage of recovery of both parameters did not differ between the groups. Patients in group II showed a significantly faster onset of movement compared with those in group I (62 ± 4.6 days versus 136 ± 7.4 days, p = 0.013). Reanimation of short-term facial paralysis can be satisfactorily addressed by means of either hemihypoglossal transposition with a nerve graft or direct masseteric-facial coaptation. However, with the latter, better symmetry and a faster onset of movement are observed. In addition, masseteric nerve transfer avoids morbidity from nerve graft harvesting. Therapeutic, III.

Comparison of hemihypoglossal-facial nerve transposition with a cross-facial nerve graft and muscle transplant for the rehabilitation of facial paralysis using the facial clima method.

PubMed

Hontanilla, Bernardo; Vila, Antonio

2012-02-01

To compare quantitatively the results obtained after hemihypoglossal nerve transposition and microvascular gracilis transfer associated with a cross facial nerve graft (CFNG) for reanimation of a paralysed face, 66 patients underwent hemihypoglossal transposition (n = 25) or microvascular gracilis transfer and CFNG (n = 41). The commissural displacement (CD) and commissural contraction velocity (CCV) in the two groups were compared using the system known as Facial clima. There was no inter-group variability between the groups (p > 0.10) in either variable. However, intra-group variability was detected between the affected and healthy side in the transposition group (p = 0.036 and p = 0.017, respectively). The transfer group had greater symmetry in displacement of the commissure (CD) and commissural contraction velocity (CCV) than the transposition group and patients were more satisfied. However, the transposition group had correct symmetry at rest but more asymmetry of CCV and CD when smiling.

Netrin1/DCC signaling promotes neuronal migration in the dorsal spinal cord.

PubMed

Junge, Harald J; Yung, Andrea R; Goodrich, Lisa V; Chen, Zhe

2016-10-26

Newborn neurons often migrate before undergoing final differentiation, extending neurites, and forming synaptic connections. Therefore, neuronal migration is crucial for establishing neural circuitry during development. In the developing spinal cord, neuroprogenitors first undergo radial migration within the ventricular zone. Differentiated neurons continue to migrate tangentially before reaching the final positions. The molecular pathways that regulate these migration processes remain largely unknown. Our previous study suggests that the DCC receptor is important for the migration of the dorsal spinal cord progenitors and interneurons. In this study, we determined the involvement of the Netrin1 ligand and the ROBO3 coreceptor in the migration. By pulse labeling neuroprogenitors with electroporation, we examined their radial migration in Netrin1 (Ntn1), Dcc, and Robo3 knockout mice. We found that all three mutants exhibit delayed migration. Furthermore, using immunohistochemistry of the BARHL2 interneuron marker, we found that the mediolateral and dorsoventral migration of differentiated dorsal interneurons is also delayed. Together, our results suggest that Netrin1/DCC signaling induce neuronal migration in the dorsal spinal cord. Netrin1, DCC, and ROBO3 have been extensively studied for their functions in regulating axon guidance in the spinal commissural interneurons. We reveal that during earlier development of dorsal interneurons including commissural neurons, these molecules play an important role in promoting cell migration.

Nkx2.1-derived astrocytes and neurons together with Slit2 are indispensable for anterior commissure formation

PubMed Central

Minocha, Shilpi; Valloton, Delphine; Ypsilanti, Athena R.; Fiumelli, Hubert; Allen, Elizabeth A.; Yanagawa, Yuchio; Marin, Oscar; Chédotal, Alain; Hornung, Jean-Pierre; Lebrand, Cécile

2015-01-01

Guidepost cells present at and surrounding the midline provide guidance cues that orient the growing axons through commissures. Here we show that the transcription factor Nkx2.1 known to control the specification of GABAergic interneurons also regulates the differentiation of astroglia and polydendrocytes within the mouse anterior commissure (AC). Nkx2.1-positive glia were found to originate from three germinal regions of the ventral telencephalon. Nkx2.1-derived glia were observed in and around the AC region by E14.5. Thereafter, a selective cell ablation strategy showed a synergistic role of Nkx2.1-derived cells, both GABAergic interneurons and astroglia, towards the proper formation of the AC. Finally, our results reveal that the Nkx2.1-regulated cells mediate AC axon guidance through the expression of the repellent cue, Slit2. These results bring forth interesting insights about the spatial and temporal origin of midline telencephalic glia, and highlight the importance of neurons and astroglia towards the formation of midline commissures. PMID:25904499

Central control of interlimb coordination and speed‐dependent gait expression in quadrupeds

PubMed Central

Danner, Simon M.; Wilshin, Simon D.; Shevtsova, Natalia A.

2016-01-01

Key points Quadrupeds express different gaits depending on speed of locomotion.Central pattern generators (one per limb) within the spinal cord generate locomotor oscillations and control limb movements. Neural interactions between these generators define interlimb coordination and gait.We present a computational model of spinal circuits representing four rhythm generators with left–right excitatory and inhibitory commissural and fore–hind inhibitory interactions within the cord.Increasing brainstem drive to all rhythm generators and excitatory commissural interneurons induces an increasing frequency of locomotor oscillations accompanied by speed‐dependent gait changes from walk to trot and to gallop and bound.The model closely reproduces and suggests explanations for multiple experimental data, including speed‐dependent gait transitions in intact mice and changes in gait expression in mutants lacking certain types of commissural interneurons. The model suggests the possible circuit organization in the spinal cord and proposes predictions that can be tested experimentally. Abstract As speed of locomotion is increasing, most quadrupeds, including mice, demonstrate sequential gait transitions from walk to trot and to gallop and bound. The neural mechanisms underlying these transitions are poorly understood. We propose that the speed‐dependent expression of different gaits results from speed‐dependent changes in the interactions between spinal circuits controlling different limbs and interlimb coordination. As a result, the expression of each gait depends on (1) left–right interactions within the spinal cord mediated by different commissural interneurons (CINs), (2) fore–hind interactions on each side of the spinal cord and (3) brainstem drives to rhythm‐generating circuits and CIN pathways. We developed a computational model of spinal circuits consisting of four rhythm generators (RGs) with bilateral left–right interactions mediated by V0 CINs (V0D and V0V sub‐types) providing left–right alternation, and conditional V3 CINs promoting left–right synchronization. Fore and hind RGs mutually inhibited each other. We demonstrate that linearly increasing excitatory drives to the RGs and V3 CINs can produce a progressive increase in the locomotor speed accompanied by sequential changes of gaits from walk to trot and to gallop and bound. The model closely reproduces and suggests explanations for the speed‐dependent gait expression observed in vivo in intact mice and in mutants lacking V0V or all V0 CINs. Specifically, trot is not expressed after removal of V0V CINs, and only bound is expressed after removal of all V0 CINs. The model provides important insights into the organization of spinal circuits and neural control of locomotion. PMID:27633893

An experimental model for the study of cognitive disorders: the hippocampus and associative learning in mice.

PubMed

Delgado-García, José M; Gruart, Agnès

2008-12-01

The availability of transgenic mice mimicking selective human neurodegenerative and psychiatric disorders calls for new electrophysiological and microstimulation techniques capable of being applied in vivo in this species. In this article, we will concentrate on experiments and techniques developed in our laboratory during the past few years. Thus we have developed different techniques for the study of learning and memory capabilities of wild-type and transgenic mice with deficits in cognitive functions, using classical conditioning procedures. These techniques include different trace (tone/SHOCK and shock/SHOCK) conditioning procedures ? that is, a classical conditioning task involving the cerebral cortex, including the hippocampus. We have also developed implantation and recording techniques for evoking long-term potentiation (LTP) in behaving mice and for recording the evolution of field excitatory postsynaptic potentials (fEPSP) evoked in the hippocampal CA1 area by the electrical stimulation of the commissural/Schaffer collateral pathway across conditioning sessions. Computer programs have also been developed to quantify the appearance and evolution of eyelid conditioned responses and the slope of evoked fEPSPs. According to the present results, the in vivo recording of the electrical activity of selected hippocampal sites during classical conditioning of eyelid responses appears to be a suitable experimental procedure for studying learning capabilities in genetically modified mice, and an excellent model for the study of selected neuropsychiatric disorders compromising cerebral cortex functioning.

Early glottic cancer involving the anterior commissure treated by transoral laser cordectomy.

PubMed

Hoffmann, Caroline; Cornu, Nicolas; Hans, Stéphane; Sadoughi, Babak; Badoual, Cécile; Brasnu, Daniel

2016-08-01

Anterior commissure involvement is considered to be a risk factor for poorer outcomes after transoral laser cordectomy (TLC) for early glottic cancer. The objective of this study was to determine the outcomes and relevance of the tumor-node-metastasis (TNM) classification in a large series of patients with early glottic cancer involving the anterior commissure treated by TLC. The clinical and surgical parameters, as well as follow-up results, of the patients treated consecutively for early-stage glottic squamous cell carcinoma involving the anterior commissure (Tis, T1a, T1b, and T2) by transoral CO2 laser cordectomy in an urban academic medical center from January 2001 to March 2013 were analyzed retrospectively. The main outcomes measures were: 5-year disease free survival (DFS), ultimate local control with laser alone, laryngeal preservation, overall-survival (OS) rates, and disease-specific survival (DSS) rates (Kaplan-Meier). Ninety-six patients treated from January 2001 to March 2013 were included. The 5-year DFS and ultimate local control with laser alone rates were 61.7% and 74.4%, respectively. The laryngeal preservation rate was 93.4%; and the OS and DSS rates were 79.2% and 91.5%, respectively. Postoperative T classification (pT) status was not found to be a significant predictor of recurrences, but was predictive of more severe recurrences requiring other treatments than laser. TLC is an effective treatment for early stage glottic cancer involving the anterior commissure. The TNM classification is a relevant prognosis factor for severe recurrences. 4. Laryngoscope, 126:1817-1822, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Comparative study of 2 commissural dorsal flap techniques for the treatment of congenital syndactyly.

PubMed

Mallet, Cindy; Ilharreborde, Brice; Jehanno, Pascal; Litzelmann, Estelle; Valenti, Philippe; Mazda, Keyvan; Penneçot, Georges-François; Fitoussi, Franck

2013-03-01

Many commissural reconstruction techniques have been described for the treatment of syndactyly. This study is the first to compare long-term results of 2 commissural dorsal flap procedures (T-flap and omega-flap). Fifty-nine web-spaces in 39 patients, operated on between 1991 and 2008, were retrospectively analyzed. Thirty-six T-flap and 23 omega-flap procedures were performed using full-thickness skin graft in every case for digital resurfacing. Factors that could affect the long-term outcome were collected, including development of web-creep, clinodactyly, and flexion contracture. Patients were reviewed with a mean follow-up of 5 years and 8 months. Preoperative complexity of syndactyly influenced the development of clinodactyly and flexion contracture. Among the patients who developed clinodactyly, 96% had surgery for complex syndactyly. No difference was found between the 2 flap methods concerning digital deformation and mobility. However, web-creep occurred more frequently after T-flap than after omega-flap procedures (17% vs. 5%). The combination of either dorsal commissural T-flaps or omega-flaps with full-thickness graft to resurface digits is a reliable technique for the treatment of syndactyly with satisfactory functional and cosmetic results. Long-term results are not influenced by the type of flap. Nevertheless, the omega-flap technique, using 2 triangular lateral-palmar flaps, avoids use of skin graft to cover lateral-palmar aspects of the new commissure, consequently reducing the incidence of web-creep. In cases of syndactyly, the primary prognostic factor is whether the patient has simple or complex syndactyly. In complex syndactyly, the risk of long-term unfavorable results is higher. When complex complicated syndactyly is involved, postoperative complication rates increase. Level III.

Organization of the sleep-related neural systems in the brain of the harbour porpoise (Phocoena phocoena).

PubMed

Dell, Leigh-Anne; Patzke, Nina; Spocter, Muhammad A; Siegel, Jerome M; Manger, Paul R

2016-07-01

The present study provides the first systematic immunohistochemical neuroanatomical investigation of the systems involved in the control and regulation of sleep in an odontocete cetacean, the harbor porpoise (Phocoena phocoena). The odontocete cetaceans show an unusual form of mammalian sleep, with unihemispheric slow waves, suppressed REM sleep, and continuous bodily movement. All the neural elements involved in sleep regulation and control found in bihemispheric sleeping mammals were present in the harbor porpoise, with no specific nuclei being absent, and no novel nuclei being present. This qualitative similarity of nuclear organization relates to the cholinergic, noradrenergic, serotonergic, and orexinergic systems and is extended to the γ-aminobutyric acid (GABA)ergic elements involved with these nuclei. Quantitative analysis of the cholinergic and noradrenergic nuclei of the pontine region revealed that in comparison with other mammals, the numbers of pontine cholinergic (126,776) and noradrenergic (122,878) neurons are markedly higher than in other large-brained bihemispheric sleeping mammals. The diminutive telencephalic commissures (anterior commissure, corpus callosum, and hippocampal commissure) along with an enlarged posterior commissure and supernumerary pontine cholinergic and noradrenergic neurons indicate that the control of unihemispheric slow-wave sleep is likely to be a function of interpontine competition, facilitated through the posterior commissure, in response to unilateral telencephalic input related to the drive for sleep. In addition, an expanded peripheral division of the dorsal raphe nuclear complex appears likely to play a role in the suppression of REM sleep in odontocete cetaceans. Thus, the current study provides several clues to the understanding of the neural control of the unusual sleep phenomenology present in odontocete cetaceans. J. Comp. Neurol. 524:1999-2017, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Efficacy of treating children with anterior commissure and true vocal fold respiratory papilloma with the 585-nm pulsed-dye laser.

PubMed

Hartnick, Christopher J; Boseley, Mark E; Franco, Ramon A; Cunningham, Michael J; Pransky, Seth

2007-02-01

To report preliminary results regarding the safety and efficacy of the 585-nm pulsed-dye laser (PDL) for the treatment of juvenile-onset recurrent respiratory papillomatosis (JORRP) in the pediatric population. Prospective longitudinal cohort study. Two pediatric otolaryngology referral centers. Twenty-three pediatric patients ranging in age from 6 months to 17 years. The 585-nm PDL was used for at least 1 treatment on each of these patients to treat JORRP of the true vocal folds or anterior commissure. Complications from the use of the 585-nm PDL in the treatment of JORRP. There was no evidence of anterior commissure webbing or true vocal fold scarring in this group of 23 patients followed up for 3 months to 1 year. The 585-nm PDL seems to be a safe instrument for treatment of JORRP. There is the potential that improved voice outcomes may be apparent when compared with traditional therapies because the vocal fold epithelium seems to be unharmed when treated with this method. Furthermore, the lack of epithelial damage incurred by the 585-nm PDL should enable more aggressive surgical excision of anterior commissure disease. Further prospective longitudinal studies examining voice outcomes are needed.

[Valvuloplasty with balloon catheter in biologic prosthesis. Reality or illusion].

PubMed

Ledesma Velasco, M; Verdín Vázquez, R; Acosta Valdez, J L; Munayer Calderón, J; Salgado Escobar, J L; Arias Monroy, L; Flores Mendoza, J

1989-01-01

We performed catheter balloon valvuloplasty (CBV) on 8 stenotic operatively-excised bioprosthetic valves (2 Hancock and 6 Ionescu Shiley). Pathology of valves before CBV included degenerative changes: commissural fusion by mounds of calcific deposits (2 valves), fibrotic and focally calcified leaflets (7 valves) and stiff and thick valves (1 valve). Inflation of the balloon resulted in commissural splitting (2 valves), leaflet cracks and fractures (3 valves). Removal of the deflated balloon catheter was associated with debris dislodgement (3 valves). In one case the valve was unable to close with potential for acute regurgitation. Thus, CBV of bioprosthetic valves can split fused commissures by similar mechanisms as in native valves. CBV may fracture calcific deposits causing acute emboli. It can also disrupt the leaflets causing acute insufficiency. The findings suggest a limited role of CBV in the treatment of stenotic bioprosthetic valves in mitral and aortic position.

Structural and functional characteristics of commissural neurons in the superior colliculus of the hamster.

PubMed

Rhoades, R W; Mooney, R D; Szczepanik, A M; Klein, B G

1986-11-08

Intracellular recording and horseradish peroxidase (HRP) injection techniques were employed to delineate the structural and functional properties of superior collicular (SC) neurons in the hamster that were antidromically activated by electrical stimulation of the contralateral tectum. A total of 39 such cells were completely characterized, injected, and recovered. In ten of these, the axonal filling allowed us to reconstruct at least a portion of the terminal arborization in the SC contralateral to the labelled cell. Two of the recovered neurons were located in the stratum griseum superficiale (SGS), three were in the stratum opticum (SO), ten were in the stratum griseum intermediale (SGI), 11 were in the stratum album intermedium (SAI), 11 were in the stratum griseum profundum (SGP) and two were located in the stratum album profundum (SAP). The recovered cells were highly varied in both their morphological and their physiological characteristics. Somal areas ranged between 74 microns2 and 364 microns2, and the sample of recovered neurons included horizontal cells, narrow field vertical cells, and a variety of other multipolar neurons. Over one-third (38.5%) of the recovered cells were unresponsive, 2.6% were exclusively visual, 33.3% responded only to innocuous cutaneous stimuli, 10.2% were bimodal, 7.7% were specifically nociceptive, and 7.7% had complex (Rhoades, Mooney, and Jacquin: J. Neurosci. 3:1342-1354, '83) somatosensory receptive fields. We observed no clear-cut correlations between the structural and functional characteristics of these neurons. The conduction latencies of the commissural SC neurons ranged between 0.8 and 14.0 ms. The most rapidly conducting cells were located in the SGP and SAP. Conduction latency had a significant negative correlation with soma area. Labelled axons, in many cases, had at least one terminal arbor in a portion of the SC that was mirror symmetric with the location of the cell from which it originated. In several cases, however, commissural axons gave off a number of collaterals across the mediolateral extent of the tectum. commissural axonal terminations were visible only in the laminae ventral to the SO. Several commissural SC neurons also had extensive ipsilateral axon collaterals. Both the ipsilateral and commissural axon branches of these cells gave off en passant and terminal swellings.

Subcortical electrostimulation to identify network subserving motor control.

PubMed

Schucht, Philippe; Moritz-Gasser, Sylvie; Herbet, Guillaume; Raabe, Andreas; Duffau, Hugues

2013-11-01

Recent anatomical-functional studies have transformed our understanding of cerebral motor control away from a hierarchical structure and toward parallel and interconnected specialized circuits. Subcortical electrical stimulation during awake surgery provides a unique opportunity to identify white matter tracts involved in motor control. For the first time, this study reports the findings on motor modulatory responses evoked by subcortical stimulation and investigates the cortico-subcortical connectivity of cerebral motor control. Twenty-one selected patients were operated while awake for frontal, insular, and parietal diffuse low-grade gliomas. Subcortical electrostimulation mapping was used to search for interference with voluntary movements. The corresponding stimulation sites were localized on brain schemas using the anterior and posterior commissures method. Subcortical negative motor responses were evoked in 20/21 patients, whereas acceleration of voluntary movements and positive motor responses were observed in three and five patients, respectively. The majority of the stimulation sites were detected rostral of the corticospinal tract near the vertical anterior-commissural line, and additional sites were seen in the frontal and parietal white matter. The diverse interferences with motor function resulting in inhibition and acceleration imply a modulatory influence of the detected fiber network. The subcortical stimulation sites were distributed veil-like, anterior to the primary motor fibers, suggesting descending pathways originating from premotor areas known for negative motor response characteristics. Further stimulation sites in the parietal white matter as well as in the anterior arm of the internal capsule indicate a large-scale fronto-parietal motor control network. Copyright © 2012 Wiley Periodicals, Inc.

Automatic evaluation of the Valsalva sinuses from cine-MRI

NASA Astrophysics Data System (ADS)

Blanchard, Cédric; Sliwa, Tadeusz; Lalande, Alain; Mohan, Pauliah; Bouchot, Olivier; Voisin, Yvon

2011-03-01

MRI appears to be particularly attractive for the study of the Sinuses of Valsalva (SV), however there is no global consensus on their suitable measurements. In this paper, we propose a new method, based on the mathematical morphology and combining a numerical geodesic reconstruction with an area estimation, to automatically evaluate the SV from a cine-MRI in a cross-sectional orientation. It consists in the extraction of the shape of the SV, the detection of relevant points (commissures, cusps and the centre of the SV), the measurement of relevant distances and in a classification of the valve as bicuspid or tricuspid by a metric evaluation of the SV. Our method was tested on 23 patient examinations and radii calculations were compared with a manual measurement. The classification of the valve as tricuspid or bicuspid was correct for all the cases. Moreover, there are an excellent correlation and an excellent concordance between manual and automatic measurements for images at diastolic phase (r= 0.97; y = x - 0.02; p=NS; mean of differences = -0.1 mm; standard deviation of differences = 2.3 mm) and at systolic phase (r= 0.96; y = 0.97 x + 0.80; p=NS ; mean of differences = -0.1 mm; standard deviation of differences = 2.4 mm). The cross-sectional orientation of the image acquisition plane conjugated with our automatic method provides a reliable morphometric evaluation of the SV, based on the automatic location of the centre of the SV, the commissure and the cusp positions. Measurements of distances between relevant points allow a precise evaluation of the SV.

Effects of suture position on left ventricular fluid mechanics under mitral valve edge-to-edge repair.

PubMed

Du, Dongxing; Jiang, Song; Wang, Ze; Hu, Yingying; He, Zhaoming

2014-01-01

Mitral valve (MV) edge-to-edge repair (ETER) is a surgical procedure for the correction of mitral valve regurgitation by suturing the free edge of the leaflets. The leaflets are often sutured at three different positions: central, lateral and commissural portions. To study the effects of position of suture on left ventricular (LV) fluid mechanics under mitral valve ETER, a parametric model of MV-LV system during diastole was developed. The distribution and development of vortex and atrio-ventricular pressure under different suture position were investigated. Results show that the MV sutured at central and lateral in ETER creates two vortex rings around two jets, compared with single vortex ring around one jet of the MV sutured at commissure. Smaller total orifices lead to a higher pressure difference across the atrio-ventricular leaflets in diastole. The central suture generates smaller wall shear stresses than the lateral suture, while the commissural suture generated the minimum wall shear stresses in ETER.

Suspension string: a new method of aortic valvuloplasty for aortic insufficiency and ventricular septal defect.

PubMed

Huang, Zhixiong

2006-09-01

In a 4-year-old boy with ventricular septal defect, severe aortic insufficiency, and mild infundibular stenosis, a new method was used to reconstruct the prolapsed aortic cusp. Two ends of a pledged stitch were passed through the aorta at each side of the right, noncoronary commissure and then through another pledget, and were then tied repeatedly in a row. The length of the row of knots was equal to that of the free edge of left coronary or noncoronary leaflet. The remainder of the stitch was passed through a pledget and then the aortic wall at each side of the left and right coronary commissure to the extraaortic wall pledget and were tied. A suspension string was formed by the row of knots and supported by a Teflon (Dupont Teflon, Wilmington, DE) felt pledget sandwich at each of two commissures. The free margin of the prolapsed cusp was attached to the suspension string by a continuous suture. The concomitant anomalies were corrected. The result was satisfactory.

Sonic hedgehog regulates its own receptor on postcrossing commissural axons in a glypican1-dependent manner.

PubMed

Wilson, Nicole H; Stoeckli, Esther T

2013-08-07

Upon reaching their intermediate target, the floorplate, commissural axons acquire responsiveness to repulsive guidance cues, allowing the axons to exit the midline and adopt a contralateral, longitudinal trajectory. The molecular mechanisms that regulate this switch from attraction to repulsion remain poorly defined. Here, we show that the heparan sulfate proteoglycan Glypican1 (GPC1) is required as a coreceptor for the Shh-dependent induction of Hedgehog-interacting protein (Hhip) in commissural neurons. In turn, Hhip is required for postcrossing axons to respond to a repulsive anteroposterior Shh gradient. Thus, Shh is a cue with dual function. In precrossing axons it acts as an attractive guidance molecule in a transcription-independent manner. At the same time, Shh binds to GPC1 to induce the expression of its own receptor, Hhip, which mediates the repulsive response of postcrossing axons to Shh. Our study characterizes a molecular mechanism by which navigating axons switch their responsiveness at intermediate targets. Copyright © 2013 Elsevier Inc. All rights reserved.

Integration of shallow gradients of Shh and Netrin-1 guides commissural axons.

PubMed

Sloan, Tyler F W; Qasaimeh, Mohammad A; Juncker, David; Yam, Patricia T; Charron, Frédéric

2015-03-01

During nervous system development, gradients of Sonic Hedgehog (Shh) and Netrin-1 attract growth cones of commissural axons toward the floor plate of the embryonic spinal cord. Mice defective for either Shh or Netrin-1 signaling have commissural axon guidance defects, suggesting that both Shh and Netrin-1 are required for correct axon guidance. However, how Shh and Netrin-1 collaborate to guide axons is not known. We first quantified the steepness of the Shh gradient in the spinal cord and found that it is mostly very shallow. We then developed an in vitro microfluidic guidance assay to simulate these shallow gradients. We found that axons of dissociated commissural neurons respond to steep but not shallow gradients of Shh or Netrin-1. However, when we presented axons with combined Shh and Netrin-1 gradients, they had heightened sensitivity to the guidance cues, turning in response to shallower gradients that were unable to guide axons when only one cue was present. Furthermore, these shallow gradients polarized growth cone Src-family kinase (SFK) activity only when Shh and Netrin-1 were combined, indicating that SFKs can integrate the two guidance cues. Together, our results indicate that Shh and Netrin-1 synergize to enable growth cones to sense shallow gradients in regions of the spinal cord where the steepness of a single guidance cue is insufficient to guide axons, and we identify a novel type of synergy that occurs when the steepness (and not the concentration) of a guidance cue is limiting.

Outcome of a graduated minimally invasive facial reanimation in patients with facial paralysis.

PubMed

Holtmann, Laura C; Eckstein, Anja; Stähr, Kerstin; Xing, Minzhi; Lang, Stephan; Mattheis, Stefan

2017-08-01

Peripheral paralysis of the facial nerve is the most frequent of all cranial nerve disorders. Despite advances in facial surgery, the functional and aesthetic reconstruction of a paralyzed face remains a challenge. Graduated minimally invasive facial reanimation is based on a modular principle. According to the patients' needs, precondition, and expectations, the following modules can be performed: temporalis muscle transposition and facelift, nasal valve suspension, endoscopic brow lift, and eyelid reconstruction. Applying a concept of a graduated minimally invasive facial reanimation may help minimize surgical trauma and reduce morbidity. Twenty patients underwent a graduated minimally invasive facial reanimation. A retrospective chart review was performed with a follow-up examination between 1 and 8 months after surgery. The FACEgram software was used to calculate pre- and postoperative eyelid closure, the level of brows, nasal, and philtral symmetry as well as oral commissure position at rest and oral commissure excursion with smile. As a patient-oriented outcome parameter, the Glasgow Benefit Inventory questionnaire was applied. There was a statistically significant improvement in the postoperative score of eyelid closure, brow asymmetry, nasal asymmetry, philtral asymmetry as well as oral commissure symmetry at rest (p < 0.05). Smile evaluation revealed no significant change of oral commissure excursion. The mean Glasgow Benefit Inventory score indicated substantial improvement in patients' overall quality of life. If a primary facial nerve repair or microneurovascular tissue transfer cannot be applied, graduated minimally invasive facial reanimation is a promising option to restore facial function and symmetry at rest.

Integration of Shallow Gradients of Shh and Netrin-1 Guides Commissural Axons

PubMed Central

Sloan, Tyler F. W.; Qasaimeh, Mohammad A.; Juncker, David; Yam, Patricia T.; Charron, Frédéric

2015-01-01

During nervous system development, gradients of Sonic Hedgehog (Shh) and Netrin-1 attract growth cones of commissural axons toward the floor plate of the embryonic spinal cord. Mice defective for either Shh or Netrin-1 signaling have commissural axon guidance defects, suggesting that both Shh and Netrin-1 are required for correct axon guidance. However, how Shh and Netrin-1 collaborate to guide axons is not known. We first quantified the steepness of the Shh gradient in the spinal cord and found that it is mostly very shallow. We then developed an in vitro microfluidic guidance assay to simulate these shallow gradients. We found that axons of dissociated commissural neurons respond to steep but not shallow gradients of Shh or Netrin-1. However, when we presented axons with combined Shh and Netrin-1 gradients, they had heightened sensitivity to the guidance cues, turning in response to shallower gradients that were unable to guide axons when only one cue was present. Furthermore, these shallow gradients polarized growth cone Src-family kinase (SFK) activity only when Shh and Netrin-1 were combined, indicating that SFKs can integrate the two guidance cues. Together, our results indicate that Shh and Netrin-1 synergize to enable growth cones to sense shallow gradients in regions of the spinal cord where the steepness of a single guidance cue is insufficient to guide axons, and we identify a novel type of synergy that occurs when the steepness (and not the concentration) of a guidance cue is limiting. PMID:25826604

Short-term and long-term memory deficits in handedness learning in mice with absent corpus callosum and reduced hippocampal commissure.

PubMed

Ribeiro, Andre S; Eales, Brenda A; Biddle, Fred G

2013-05-15

The corpus callosum (CC) and hippocampal commissure (HC) are major interhemispheric connections whose role in brain function and behaviors is fascinating and contentious. Paw preference of laboratory mice is a genetically regulated, adaptive behavior, continuously shaped by training and learning. We studied variation with training in paw-preference in mice of the 9XCA/WahBid ('9XCA') recombinant inbred strain, selected for complete absence of the CC and severely reduced HC. We measured sequences of paw choices in 9XCA mice in two training sessions in unbiased test chambers, separated by one-week. We compared them with sequences of paw choices in model non-learner mice that have random unbiased paw choices and with those of C57BL/6JBid ('C57BL/6J') mice that have normal interhemispheric connections and learn a paw preference. Positive autocorrelation between successive paw choices during each session and change in paw-preference bias between sessions indicate that 9XCA mice have weak, but not null, learning skills. We tested the effect of the forebrain commissural defect on paw-preference learning with the independent BTBR T+ tf/J ('BTBR') mouse strain that has a genetically identical, non-complementing commissural trait. BTBR has weak short-term and long-term memory skills, identical to 9XCA. The results provide strong evidence that CC and HC contribute in memory function and formation of paw-preference biases. Copyright © 2013 Elsevier B.V. All rights reserved.

Enhanced Brain Connectivity in Long-term Meditation Practitioners

PubMed Central

Luders, Eileen; Clark, Kristi; Narr, Katherine L.; Toga, Arthur W.

2011-01-01

Very little is currently known about the cerebral characteristics that underlie the complex processes of meditation as only a limited number of studies have addressed this topic. Research exploring structural connectivity in meditation practitioners is particularly rare. We thus acquired diffusion tensor imaging (DTI) data of high angular and spatial resolution and used atlas-based tract mapping methods to investigate white matter fiber characteristics in a well-matched sample of long-term meditators and controls (n=54). A broad field mapping approach estimated the fractional anisotropy (FA) for twenty different fiber tracts (i.e., nine tracts in each hemisphere and two inter-hemispheric tracts) that were subsequently used as dependent measures. Results showed pronounced structural connectivity in meditators compared to controls throughout the entire brain within major projection pathways, commissural pathways, and association pathways. The largest group differences were observed within the corticospinal tract, the temporal component of the superior longitudinal fasciculus, and the uncinate fasciculus. While cross-sectional studies represent a good starting point for elucidating possible links between meditation and white matter fiber characteristics, longitudinal studies will be necessary to determine the relative contribution of nature and nurture to enhanced structural connectivity in long-term meditators. PMID:21664467

Organization of left–right coordination of neuronal activity in the mammalian spinal cord: Insights from computational modelling

PubMed Central

Shevtsova, Natalia A; Talpalar, Adolfo E; Markin, Sergey N; Harris-Warrick, Ronald M; Kiehn, Ole; Rybak, Ilya A

2015-01-01

Different locomotor gaits in mammals, such as walking or galloping, are produced by coordinated activity in neuronal circuits in the spinal cord. Coordination of neuronal activity between left and right sides of the cord is provided by commissural interneurons (CINs), whose axons cross the midline. In this study, we construct and analyse two computational models of spinal locomotor circuits consisting of left and right rhythm generators interacting bilaterally via several neuronal pathways mediated by different CINs. The CIN populations incorporated in the models include the genetically identified inhibitory (V0D) and excitatory (V0V) subtypes of V0 CINs and excitatory V3 CINs. The model also includes the ipsilaterally projecting excitatory V2a interneurons mediating excitatory drive to the V0V CINs. The proposed network architectures and CIN connectivity allow the models to closely reproduce and suggest mechanistic explanations for several experimental observations. These phenomena include: different speed-dependent contributions of V0D and V0V CINs and V2a interneurons to left–right alternation of neural activity, switching gaits between the left–right alternating walking-like activity and the left–right synchronous hopping-like pattern in mutants lacking specific neuron classes, and speed-dependent asymmetric changes of flexor and extensor phase durations. The models provide insights into the architecture of spinal network and the organization of parallel inhibitory and excitatory CIN pathways and suggest explanations for how these pathways maintain alternating and synchronous gaits at different locomotor speeds. The models propose testable predictions about the neural organization and operation of mammalian locomotor circuits. Key points Coordination of neuronal activity between left and right sides of the mammalian spinal cord is provided by several sets of commissural interneurons (CINs) whose axons cross the midline. Genetically identified inhibitory V0D and excitatory V0V CINs and ipsilaterally projecting excitatory V2a interneurons were shown to secure left–right alternation at different locomotor speeds. We have developed computational models of neuronal circuits in the spinal cord that include left and right rhythm-generating centres interacting bilaterally via three parallel pathways mediated by V0D, V2a–V0V and V3 neuron populations. The models reproduce the experimentally observed speed-dependent left–right coordination in normal mice and the changes in coordination seen in mutants lacking specific neuron classes. The models propose an explanation for several experimental results and provide insights into the organization of the spinal locomotor network and parallel CIN pathways involved in gait control at different locomotor speeds. PMID:25820677

The ontogenesis of the forebrain commissures and the determination of brain asymmetries.

PubMed

Lent, R; Schmidt, S L

1993-02-01

We have reviewed the organization and development of the interhemispheric projections through the forebrain commissures, especially those of the CC, in connection with the development of brain asymmetries. Analyzing the available data, we conclude that the developing CC plays an important role in the ontogenesis of brain asymmetries. We have extended a previous hypothesis that the rodent CC may exert a stabilizing effect over the unstable populational asymmetries of cortical size and shape, and that it participates in the developmental stabilization of lateralized motor behaviors.

Interrupted commissural band annuloplasty prevents mitral stenosis.

PubMed

Sawazaki, Masaru; Tomari, Shiro; Zaikokuji, Kenta; Imaeda, Yusuke

2016-09-01

Mitral annuloplasty is an important component of the treatment of degenerative mitral valve disease. However, postoperative echocardiography reveals elevated mitral gradients in some patients. We developed a technique that we termed interrupted commissural band annuloplasty (iCBA), which does not shorten either the anterior or posterior annulus and is not associated with the development of a mitral gradient. We compared the echocardiographic characteristics of patients treated using this method versus Cosgrove ring (COS) placement, both at rest and during exercise. ICBA features placement of three sutures in the commissures using two bands and shortens the commissural annular length by 60 %. We used this method to treat 63 patients and placed Cosgrove bands in 58. Of all patients, 48 who underwent iCBA and 34 with COSs passed the exercise echocardiographic test. The maximal transmitral pressures at rest in the iCBA and Cosgrove groups were 8.04 ± 0.74 and 11.30 ± 0.88 mmHg (P = 0.0029), respectively, and the mean transmitral pressures at rest were 2.46 ± 0.74 and 3.61 ± 0.32 mmHg (P = 0.0037), respectively. The maximal transmitral pressures during exercise were 11.79 ± 0.97 and 18.37 ± 1.16 mmHg (P < 0.0001), and the mean transmitral pressures during exercise were 4.95 ± 0.45 and 7.76 ± 0.53 mmHg (P < 0.0001). ICBA prevents postoperative mitral stenosis both at rest and importantly during exercise.

Three subdivisions of the auditory midbrain in chicks (Gallus gallus) identified by their afferent and commissural projections

PubMed Central

Wang, Yuan; Karten, Harvey J.

2010-01-01

The auditory midbrain is a site of convergence of multiple auditory channels from the brainstem. In birds, two separate ascending channels have been identified, through which time and intensity information is sent to nucleus mesencephalicus lateralis, pars dorsalis (MLd), the homologue of the central nucleus of mammalian inferior colliculus. Using in vivo anterograde and retrograde tracing techniques, the current study provides two lines of anatomical evidence supporting the presence of a third ascending channel to the chick MLd. First, three non-overlapping zones of MLd receive inputs from three distinct cell groups in the caudodorsal brainstem. The projections from nucleus angularis (NA) and nucleus laminaris (NL) are predominately contralateral and may correspond to the time and intensity channels. A rostromedial portion of MLd receives bilateral projections mainly from the Regio Intermedius, an interposed region of cells lying at a caudal level between NL and NA, as well as scattered neurons embedded in 8th nerve tract, and probably a very ventral region of NA. Second, the bilateral zones of MLd on two sides of the brain are reciprocally connected and do not interact with other zones of MLd via commissural connections. In contrast, the NL-recipient zone projects contralaterally upon the NA-recipient zone. The structural separation of the third pathway from the NA and NL projections suggests a third information-processing channel, in parallel with the time and intensity channels. Neurons in the third channel appear to process very low frequency information including infrasound, probably utilizing different mechanisms than that underlying higher frequency processing. PMID:20148439

Plasticity of Interhemispheric Temporal Lobe White Matter Pathways Due to Early Disruption of Corpus Callosum Development in Spina Bifida

PubMed Central

Juranek, Jenifer; Romanowska-Pawliczek, Anna; Hannay, H. Julia; Cirino, Paul T.; Dennis, Maureen; Kramer, Larry A.; Fletcher, Jack M.

2016-01-01

Abstract Spina bifida myelomeningocele (SBM) is commonly associated with anomalous development of the corpus callosum (CC) because of congenital partial hypogenesis and hydrocephalus-related hypoplasia. It represents a model disorder to examine the effects of early disruption of CC neurodevelopment and the plasticity of interhemispheric white matter connections. Diffusion tensor imaging was acquired on 76 individuals with SBM and 27 typically developing individuals, aged 8–36 years. Probabilistic tractography was used to isolate the interhemispheric connections between the posterior superior temporal lobes, which typically traverse the posterior third of the CC. Early disruption of CC development resulted in restructuring of interhemispheric connections through alternate commissures, particularly the anterior commissure (AC). These rerouted fibers were present in people with SBM and both CC hypoplasia and hypogenesis. In addition, microstructural integrity was reduced in the interhemispheric temporal tract in people with SBM, indexed by lower fractional anisotropy, axial diffusivity, and higher radial diffusivity. Interhemispheric temporal tract volume was positively correlated with total volume of the CC, such that more severe underdevelopment of the CC was associated with fewer connections between the posterior temporal lobes. Therefore, both the macrostructure and microstructure of this interhemispheric tract were reduced, presumably as a result of more extensive CC malformation. The current findings suggest that early disruption in CC development reroutes interhemispheric temporal fibers through both the AC and more anterior sections of the CC in support of persistent hypotheses that the AC may serve a compensatory function in atypical CC development. PMID:26798959

Neuronal Basis of Crossed Actions from the Reticular Formation on Feline Hindlimb Motoneurons

PubMed Central

Jankowska, Elzbieta; Hammar, Ingela; Slawinska, Urszula; Maleszak, Katarzyna; Edgley, Stephen A.

2007-01-01

Pathways through which reticulospinal neurons can influence contralateral limb movements were investigated by recording from mo-toneurons innervating hindlimb muscles. Reticulospinal tract fibers were stimulated within the brainstem or in the lateral funiculus of the thoracic spinal cord contralateral to the motoneurons. Effects evoked by ipsilaterally descending reticulospinal tract fibers were eliminated by a spinal hemisection at an upper lumbar level. Stimuli applied in the brainstem evoked EPSPs, IPSPs, or both at latencies of 1.42 ± 0.03 and 1.53 ± 0.04 msec, respectively, from the first components of the descending volleys and with properties indicating a disynaptic linkage, in most contralateral motoneurons: EPSPs in 76% and IPSPs in 26%. EPSPs with characteristics of monosynaptically evoked responses, attributable to direct actions of crossed axon collaterals of reticulospinal fibers, were found in a small proportion of the motoneurons, whether evoked from the brainstem (9%) or from the thoracic cord (12.5%). Commissural neurons, which might mediate the crossed disynaptic actions (i.e., were antidromically activated from contralateral motor nuclei and monosynaptically excited from the ipsilateral reticular formation), were found in Rexed’s lamina VIII in the midlumbar segments (L3–L5). The results reveal that although direct actions of reticulospinal fibers are much more potent on ipsilateral motoneurons, interneuronally mediated actions are as potent contralaterally as ipsilaterally, and midlumbar commissural neurons are likely to contribute to them. They indicate a close coupling between the spinal interneuronal systems used by the reticulospinal neurons to coordinate muscle contractions ipsilaterally and contralaterally. PMID:12629191

Distinct protein domains and expression patterns confer divergent axon guidance functions for Drosophila Robo receptors.

PubMed

Spitzweck, Bettina; Brankatschk, Marko; Dickson, Barry J

2010-02-05

The orthogonal array of axon pathways in the Drosophila CNS is constructed in part under the control of three Robo family axon guidance receptors: Robo1, Robo2 and Robo3. Each of these receptors is responsible for a distinct set of guidance decisions. To determine the molecular basis for these functional specializations, we used homologous recombination to create a series of 9 "robo swap" alleles: expressing each of the three Robo receptors from each of the three robo loci. We demonstrate that the lateral positioning of longitudinal axon pathways relies primarily on differences in gene regulation, not distinct combinations of Robo proteins as previously thought. In contrast, specific features of the Robo1 and Robo2 proteins contribute to their distinct functions in commissure formation. These specializations allow Robo1 to prevent crossing and Robo2 to promote crossing. These data demonstrate how diversification of expression and structure within a single family of guidance receptors can shape complex patterns of neuronal wiring. 2010 Elsevier Inc. All rights reserved.

Early development of the circumferential axonal pathway in mouse and chick spinal cord.

PubMed

Holley, J A

1982-03-10

The early development of the circumferential axonal pathway in the brachial and lumbar spinal cord of mouse and chick embryos was studied by scanning and transmission electron microscopy. The cellular processes which comprise this pathway grow in the transverse plane and along the lateral margin of the marginal zone (i.e., circumferentially oriented), as typified by the early embryonic commissural axons. The first formative event observed was in the ventrolateral margin of the primitive spinal cord ventricular zone. Cellular processes were found near the external limiting membrane that appeared to grow a variable distance either dorsally or ventrally. Later in development, presumptive motor column neurons migrated into the ventrolateral region, distal to these early circumferentially oriented processes. Concurrently, other circumferentially oriented perikarya and processes appeared along the dorsolateral margin. Due to their aligned sites of origin and parallel growth, the circumferential processes formed a more or less continuous line or pathway, which in about 10% of the scanned specimens could be followed along the entire lateral margin of the embryonic spinal cord. Several specimens later in development had two sets of aligned circumferential processes in the ventral region. Large numbers of circumferential axons were then found to follow the preformed pathway by fasciculation, after the primitive motor column had become established. Since the earliest circumferential processes appeared to differentiate into axons and were found nearly 24 hours prior to growth of most circumferential axons, their role in guidance as pioneering axons was suggested.

A novel method to measure mitral valve area in patients with rheumatic mitral stenosis using three-dimensional transesophageal echocardiography: Feasibility and validation.

PubMed

Mahmoud Elsayed, Hani M; Hassan, Mohamed; Nagy, Michael; Amin, Alaaeldin; Elguindy, Ahmed; Wagdy, Kerolos; Yacoub, Magdi

2018-03-01

Neither two- nor three-dimensional (3D) planimetry of the mitral valve (MV) orifice takes the mitral commissures into account. Thus, if the commissures are not completely fused, the MV orifice will not be planar, and MV area (MVA) will be underestimated. The study aimed to validate a novel method for measurement of the MVA using a software that traces the MV orifice including the commissures. The study included 30 patients undergoing percutaneous balloon mitral valvuloplasty for severe rheumatic mitral stenosis. All performed 3D transesophageal echocardiography (TEE) immediately before the procedure. MVA was measured using the mitral valve navigation (MVN) software of the Philips Q-Lab 10.2 in a diastolic frame with maximum diastolic opening of the MV. Regular 3D planimetry of the MV orifice was also performed. Before balloon dilation, the MVA was calculated invasively using the Gorlin's formula. No significant difference was detected between MVN-derived MVA and Gorlin-derived MVA (0.98 cm 2 vs. 1.0 cm 2 , P = .33). A statistically significant difference was detected between Planimetry-derived MVA and Gorlin-derived MVA (0.8 cm 2 vs. 1.0 cm 2 , P < .001). There were significant linear correlations between MVN-derived MVA and Gorlin-derived MVA (r = .84, P < .001). Using Bland-Altman analysis, Gorlin-derived MVA showed better and relatively narrower limits of agreement with MVN-derived MVA than planimetry-derived MVA. Measurement of the MVA using the MVN method is feasible and is more correlated to the invasively measured MVA than the 3D planimetry method. This is the most accurate method of measuring the MVA that takes MV commissures into account. © 2017, Wiley Periodicals, Inc.

A rhythmic modulatory gating system in the stomatogastric nervous system of Homarus gammarus. III. Rhythmic control of the pyloric CPG.

PubMed

Cardi, P; Nagy, F

1994-06-01

1. Two modulatory neurons, P and commissural pyloric (CP), known to be involved in the long-term maintenance of pyloric central pattern generator operation in the rock lobster Homarus gammarus, are members of the commissural pyloric oscillator (CPO), a higher-order oscillator influencing the pyloric network. 2. The CP neuron was endogenously oscillating in approximately 30% of the preparations in which its cell body was impaled. Rhythmic inhibitory feedback from the pyloric pacemaker anterior burster (AB) neuron stabilized the CP neuron's endogenous rhythm. 3. The organization of the CPO is described. Follower commissural neurons, the F cells, and the CP neuron receive a common excitatory postsynaptic potential from another commissural neuron, the large exciter (LE). When in oscillatory state, CP in turn excites the LE neuron. This positive feedback may maintain long episodes of CP oscillations. 4. The pyloric pacemaker neurons follow the CPO rhythm with variable coordination modes (i.e., 1:1, 1:2) and switch among these modes when their membrane potential is modified. The CPO inputs strongly constrain the pyloric period, which as a result may adopt only a few discrete values. This effect is based on mechanisms of entrainment between the CPO and the pyloric oscillator. 5. Pyloric constrictor neurons show differential sensitivity from the pyloric pacemaker neurons with respect to the CPO inputs. Consequently, their bursting period can be a shorter harmonic of the bursting period of the pyloric pacemakers neurons. 6. The CPO neurons seem to be the first example of modulatory gating neurons that also give timing cues to a rhythmic pattern generating network.

A new evaluation of heat distribution on facial skin surface by infrared thermography.

PubMed

Haddad, Denise S; Brioschi, Marcos L; Baladi, Marina G; Arita, Emiko S

2016-01-01

The aim of this study was to identify the facial areas defined by thermal gradient, in individuals compatible with the pattern of normality, and to quantify and describe them anatomically. The sample consisted of 161 volunteers, of both genders, aged between 26 and 84 years (63 ± 15 years). The results demonstrated that the thermal gradient areas suggested for the study were present in at least 95% of the thermograms evaluated and that there is significant difference in temperature between the genders, racial group and variables "odontalgia", "dental prothesis" and "history of migraine" (p < 0.05). Moreover, there was no statistically significant difference in the absolute temperatures between ages, and right and left sides of the face, in individuals compatible with the pattern of normality (ΔT = 0.11°C). The authors concluded that according to the suggested areas of thermal gradients, these were present in at least 95% of all the thermograms evaluated, and the areas of high intensity found in the face were medial palpebral commissure, labial commissure, temporal, supratrochlear and external acoustic meatus, whereas the points of low intensity were inferior labial, lateral palpebral commissure and nasolabial.

Flamingo, a seven-pass transmembrane cadherin, cooperates with Netrin/Frazzled in Drosophila midline guidance.

PubMed

Organisti, Cristina; Hein, Irina; Grunwald Kadow, Ilona C; Suzuki, Takashi

2015-01-01

During central nervous system development, several guidance cues and receptors, as well as cell adhesion molecules, are required for guiding axons across the midline and along the anterior-posterior axis. In Drosophila, commissural axons sense the midline attractants Netrin A and B (Net) through Frazzled (Fra) receptors. Despite their importance, lack of Net or fra affects only some commissures, suggesting that additional molecules can fulfill this function. Recently, planar cell polarity (PCP) proteins have been implicated in midline axon guidance in both vertebrate and invertebrate systems. Here, we report that the atypical cadherin and PCP molecule Flamingo/Starry night (Fmi/Stan) acts jointly with Net/Fra signaling during midline development. Additional removal of fmi strongly increases the guidance defects in Net/fra mutants. Rescue and domain deletion experiments suggest that Fmi signaling facilitates commissural pathfinding potentially by mediating axonal fasciculation in a partly homophilic manner. Altogether, our results indicate that contact-mediated cell adhesion via Fmi acts in addition to the Net/Fra guidance system during axon pathfinding across the midline, underlining the importance of PCP molecules during vertebrates and invertebrates midline development. © 2014 The Authors Genes to Cells © 2014 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

A new evaluation of heat distribution on facial skin surface by infrared thermography

PubMed Central

Brioschi, Marcos L; Baladi, Marina G; Arita, Emiko S

2016-01-01

Objective: The aim of this study was to identify the facial areas defined by thermal gradient, in individuals compatible with the pattern of normality, and to quantify and describe them anatomically. Methods: The sample consisted of 161 volunteers, of both genders, aged between 26 and 84 years (63 ± 15 years). Results: The results demonstrated that the thermal gradient areas suggested for the study were present in at least 95% of the thermograms evaluated and that there is significant difference in temperature between the genders, racial group and variables “odontalgia”, “dental prothesis” and “history of migraine” (p < 0.05). Moreover, there was no statistically significant difference in the absolute temperatures between ages, and right and left sides of the face, in individuals compatible with the pattern of normality (ΔT = 0.11°C). Conclusions: The authors concluded that according to the suggested areas of thermal gradients, these were present in at least 95% of all the thermograms evaluated, and the areas of high intensity found in the face were medial palpebral commissure, labial commissure, temporal, supratrochlear and external acoustic meatus, whereas the points of low intensity were inferior labial, lateral palpebral commissure and nasolabial. PMID:26891669

Lengthening temporalis myoplasty: a surgical tool for dynamic labial commissure reanimation.

PubMed

Guerreschi, Pierre; Labbe, Daniel

2015-04-01

Lengthening temporalis myoplasty (LTM), first described by Labbé in 1997, ensures the transfers of the entire temporal muscle from the coronoid process to the upper half of the lip without interposition of aponeurotic tissue. The temporal muscle changes function because it is entirely mobilized toward another effector: the labial commissure. Thanks to brain plasticity, the muscle loses its chewing function, and after 6 months of speech rehabilitation it acquires its new smiling function. We describe technical points especially the coronoid process approaches both through an upper temporal fossa approach and a lower nasolabial fold approach. Rehabilitation starts 3 weeks after the surgery following a standardized protocol to move from a mandibular smile to a voluntary, then spontaneous, smile in three steps. The LTM is the main part of a one-stage global treatment of the paralyzed face. It constitutes a dynamic palliative treatment usually started at the sequelae stage, 18 month after the outcome of a peripheral facial paralysis. This one-stage procedure is a reproducible and relevant surgical technique in the difficult treatment of peripheral facial paralysis. It allows implementing an active muscle transfer to reanimate the labial commissure and re-create a mobile nasolabial fold. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A robust, efficient and flexible method for staining myelinated axons in blocks of brain tissue.

PubMed

Wahlsten, Douglas; Colbourne, Frederick; Pleus, Richard

2003-03-15

Previous studies have demonstrated the utility of the gold chloride method for en bloc staining of a bisected brain in mice and rats. The present study explores several variations in the method, assesses its reliability, and extends the limits of its application. We conclude that the method is very efficient, highly robust, sufficiently accurate for most purposes, and adaptable to many morphometric measures. We obtained acceptable staining of commissures in every brain, despite a wide variety of fixation methods. One-half could be stained 24 h after the brain was extracted and the other half could be stained months later. When staining failed because of an exhausted solution, the brain could be stained successfully in fresh solution. Relatively small changes were found in the sizes of commissures several weeks after initial fixation or staining. A half brain stained to reveal the mid-sagittal section could then be sectioned coronally and stained again in either gold chloride for myelin or cresyl violet for Nissl substance. Uncertainty, arising from pixelation of digitized images was far less than errors arising from human judgments about the histological limits of major commissures. Useful data for morphometric analysis were obtained by scanning the surface of a gold chloride stained block of brain with an inexpensive flatbed scanner.

Cholinergic, serotoninergic and peptidergic components of the nervous system of Discocotyle sagittata (Monogenea:Polyopisthocotylea).

PubMed

Cable, J; Marks, N J; Halton, D W; Shaw, C; Johnston, C F; Tinsley, R C; Gannicott, A M

1996-12-01

Cholinergic, serotoninergic (5-HT) and peptidergic neuronal pathways have been demonstrated in both central and peripheral nervous systems of adult Discocotyle sagittata, using enzyme histochemistry and indirect immunocytochemistry in conjunction with confocal scanning laser microscopy. Antisera to 2 native flatworm neuropeptides, neuropeptide F and the FMRFamide-related peptide (FaRP), GNFFRFamide, were employed to detect peptide immunoreactivity. The CNS is composed of paired cerebral ganglia and connecting dorsal commissure, together with several paired longitudinal nerve cords. The main longitudinal nerve cords (lateral, ventral and dorsal) are interconnected at intervals by a series of annular cross-connectives, producing a ladder-like arrangement typical of the platyhelminth nervous system. At the level of the haptor, the ventral cords provide nerve roots which innervate each of the 9 clamps. Cholinergic and peptidergic neuronal organisation was similar, but distinct from that of the serotoninergic components. The PNS and reproductive system are predominantly innervated by peptidergic neurones.

Spinal cord neuron classes in embryos of the smooth newt Triturus vulgaris: a horseradish peroxidase and immunocytochemical study.

PubMed

Harper, C E; Roberts, A

1993-04-29

Spinal cord neurons were investigated in embryos of Triturus vulgaris, the smooth newt, just prior to hatching. These embryos can swim if freed from their egg membranes. Horseradish peroxidase (HRP) labelling, together with GABA and glycine immunocytochemistry (ICC), revealed nine distinct anatomical classes of neuron. 1. Ventrolateral motoneurons with mainly dorsal dendrites, sometimes a descending central axon and peripheral axon innervating the trunk muscles. 2. Dorsal primary sensory Rohon-Beard neurons innervating skin and with dorsal ascending and descending axons in spinal cord. 3. Commissural interneurons with mid-cord unipolar soma, glycine-like immunoreactivity, dendrites on initial segment of ventral axon which crosses cord to ascend or branch. 4. Dorsolateral commissural interneurons with multipolar soma in dorsolateral position with dorsal dendrites and ventral axon which crosses and ascends or branches. 5. Giant dorsolateral commissural interneurons with large dorsolateral somata widely spaced (130-250 microns spacing) with process projecting dorsally to other side, dorsolateral dendrites and ventral axon which crosses to ascend and branch. 6. Dorsolateral ascending interneurons in dorsolateral position with multipolar soma and ascending axon on same side. 7. Ascending interneurons with unipolar soma, GABA-like immunoreactivity and ascending axon on same side. 8. Descending interneurons with bi- or multi-polar soma, extensive dorsal and ventral dendrites, and descending axon on same side. They may also have ascending axons. 9. Kolmer-Agduhr cerebrospinal fluid contacting neurons with cilia and microvilli in lateral corners of neural canal. GABA-like immunoreactivity, no dendrites and ascending axon. Eight of the nine cells classes were found to bear a marked resemblance to neurons previously described in zebrafish and Xenopus embryos in terms of their anatomy, distribution and immunoreactivity to GABA and glycine. Homologies and possible functions are discussed. Giant dorsolateral commissural neurons, were not found in Xenopus or teleosts but were present in Ambystoma mexicanum and Neoceratodus. The regular, possibly segmental longitudinal distribution pattern of these cells within the cord is unusual among amphibian spinal neurons.

The Relationship between Neurite Density Measured with Confocal Microscopy in a Cleared Mouse Brain and Metrics Obtained from Diffusion Tensor and Diffusion Kurtosis Imaging

PubMed Central

Irie, Ryusuke; Kamagata, Koji; Kerever, Aurelien; Ueda, Ryo; Yokosawa, Suguru; Otake, Yosuke; Ochi, Hisaaki; Yoshizawa, Hidekazu; Hayashi, Ayato; Tagawa, Kazuhiko; Okazawa, Hitoshi; Takahashi, Kohske; Sato, Kanako; Hori, Masaaki; Arikawa-Hirasawa, Eri; Aoki, Shigeki

2018-01-01

Purpose: Diffusional kurtosis imaging (DKI) enables sensitive measurement of tissue microstructure by quantifying the non-Gaussian diffusion of water. Although DKI is widely applied in many situations, histological correlation with DKI analysis is lacking. The purpose of this study was to determine the relationship between DKI metrics and neurite density measured using confocal microscopy of a cleared mouse brain. Methods: One thy-1 yellow fluorescent protein 16 mouse was deeply anesthetized and perfusion fixation was performed. The brain was carefully dissected out and whole-brain MRI was performed using a 7T animal MRI system. DKI and diffusion tensor imaging (DTI) data were obtained. After the MRI scan, brain sections were prepared and then cleared using aminoalcohols (CUBIC). Confocal microscopy was performed using a two-photon confocal microscope with a laser. Forty-eight ROIs were set on the caudate putamen, seven ROIs on the anterior commissure, and seven ROIs on the ventral hippocampal commissure on the confocal microscopic image and a corresponding MR image. In each ROI, histological neurite density and the metrics of DKI and DTI were calculated. The correlations between diffusion metrics and neurite density were analyzed using Pearson correlation coefficient analysis. Results: Mean kurtosis (MK) (P = 5.2 × 10−9, r = 0.73) and radial kurtosis (P = 2.3 × 10−9, r = 0.74) strongly correlated with neurite density in the caudate putamen. The correlation between fractional anisotropy (FA) and neurite density was moderate (P = 0.0030, r = 0.42). In the anterior commissure and the ventral hippocampal commissure, neurite density and FA are very strongly correlated (P = 1.3 × 10−5, r = 0.90). MK in these areas were very high value and showed no significant correlation (P = 0.48). Conclusion: DKI accurately reflected neurite density in the area with crossing fibers, potentially allowing evaluation of complex microstructures. PMID:29213008

The Relationship between Neurite Density Measured with Confocal Microscopy in a Cleared Mouse Brain and Metrics Obtained from Diffusion Tensor and Diffusion Kurtosis Imaging.

PubMed

Irie, Ryusuke; Kamagata, Koji; Kerever, Aurelien; Ueda, Ryo; Yokosawa, Suguru; Otake, Yosuke; Ochi, Hisaaki; Yoshizawa, Hidekazu; Hayashi, Ayato; Tagawa, Kazuhiko; Okazawa, Hitoshi; Takahashi, Kohske; Sato, Kanako; Hori, Masaaki; Arikawa-Hirasawa, Eri; Aoki, Shigeki

2018-04-10

Diffusional kurtosis imaging (DKI) enables sensitive measurement of tissue microstructure by quantifying the non-Gaussian diffusion of water. Although DKI is widely applied in many situations, histological correlation with DKI analysis is lacking. The purpose of this study was to determine the relationship between DKI metrics and neurite density measured using confocal microscopy of a cleared mouse brain. One thy-1 yellow fluorescent protein 16 mouse was deeply anesthetized and perfusion fixation was performed. The brain was carefully dissected out and whole-brain MRI was performed using a 7T animal MRI system. DKI and diffusion tensor imaging (DTI) data were obtained. After the MRI scan, brain sections were prepared and then cleared using aminoalcohols (CUBIC). Confocal microscopy was performed using a two-photon confocal microscope with a laser. Forty-eight ROIs were set on the caudate putamen, seven ROIs on the anterior commissure, and seven ROIs on the ventral hippocampal commissure on the confocal microscopic image and a corresponding MR image. In each ROI, histological neurite density and the metrics of DKI and DTI were calculated. The correlations between diffusion metrics and neurite density were analyzed using Pearson correlation coefficient analysis. Mean kurtosis (MK) (P = 5.2 × 10 -9 , r = 0.73) and radial kurtosis (P = 2.3 × 10 -9 , r = 0.74) strongly correlated with neurite density in the caudate putamen. The correlation between fractional anisotropy (FA) and neurite density was moderate (P = 0.0030, r = 0.42). In the anterior commissure and the ventral hippocampal commissure, neurite density and FA are very strongly correlated (P = 1.3 × 10 -5 , r = 0.90). MK in these areas were very high value and showed no significant correlation (P = 0.48). DKI accurately reflected neurite density in the area with crossing fibers, potentially allowing evaluation of complex microstructures.

Effects of inhaled anesthetic isoflurane on long-term potentiation of CA3 pyramidal cell afferents in vivo

PubMed Central

Ballesteros, Kristen A; Sikorski, Angela; Orfila, James E; Martinez, Joe L

2012-01-01

Isoflurane is a preferred anesthetic, due to its properties that allow a precise concentration to be delivered continually during in vivo experimentation. The major mechanism of action of isoflurane is modulation of the γ-amino butyric acid (GABAA) receptor-chloride channel, mediating inhibitory synaptic transmission. Animal studies have shown that isoflurane does not cause cell death, but it does inhibit cell growth and causes long-term hippocampal learning deficits. As there are no studies characterizing the effects of isoflurane on electrophysiological aspects of long-term potentiation (LTP) in the hippocampus, it is important to determine whether isoflurane alters the characteristic responses of hippocampal afferents to cornu ammonis region 3 (CA3). We investigated the effects of isoflurane on adult male rats during in vivo induction of LTP, using the mossy fiber pathway, the lateral perforant pathway, the medial perforant pathway, and the commissural CA3 (cCA3) to CA3, with intracranial administration of Ringer’s solution, naloxone, RS-aminoindan-1, 5-dicarboxylic acid (AIDA), or 3-[(R)-2-carboxypiperazin-4-yl]-propo-2-enyl-1-phosphonic acid (CPP). Then, we compared these responses to published electrophysiological data, using sodium pentobarbital as an anesthetic, under similar experimental conditions. Our results showed that LTP was exhibited in animals anesthetized with isoflurane under vehicle conditions. With the exception of AIDA in the lateral perforant pathway, the defining characteristics of the four pathways appeared to remain intact, except for the observation that LTP was markedly reduced in animals anesthetized with isoflurane compared to those anesthetized with sodium pentobarbital. The results suggest that isoflurane may affect amplitude through activation of GABAA receptors or mechanisms important to LTP in CA3 afferent fibers. PMID:23204857

Inter-ethnic differences in valve morphology, valvular dysfunction, and aortopathy between Asian and European patients with bicuspid aortic valve.

PubMed

Kong, William K F; Regeer, Madelien V; Poh, Kian K; Yip, James W; van Rosendael, Philippe J; Yeo, Tiong C; Tay, Edgar; Kamperidis, Vasileios; van der Velde, Enno T; Mertens, Bart; Ajmone Marsan, Nina; Delgado, Victoria; Bax, Jeroen J

2018-04-14

Transcatheter aortic valve replacement (TAVR) has been shown safe and feasible in patients with bicuspid aortic valve (BAV) morphology. Evaluation of inter-ethnic differences in valve morphology and function and aortic root dimensions in patients with BAV is important for the worldwide spread of this therapy in this subgroup of patients. Comparisons between large European and Asian cohorts of patients with BAV have not been performed, and potential differences between populations may have important implications for TAVR. The present study evaluated the differences in valve morphology and function and aortic root dimensions between two large cohorts of European and Asian patients with BAV. Aortic valve morphology was defined on transthoracic echocardiography according to the number of commissures and raphe: type 0 = no raphe and two commissures, type 1 = one raphe and two commissures, type 2 = two raphes and one commissure. Aortic stenosis and regurgitation were graded according to current recommendations. For this study, aortic root dimensions were manually measured on transthoracic echocardiograms at the level of the aortic annulus, sinus of Valsalva (SOV), sinotubular junction (STJ), and ascending aorta (AA). Of 1427 patients with BAV (45.2 ± 18.1 years, 71.9% men), 794 (55.6%) were Europeans and 633 (44.4%) were Asians. The groups were comparable in age and proportion of male sex. Asians had higher prevalence of type 1 BAV with raphe between right and non-coronary cusps than Europeans (19.7% vs. 13.6%, respectively; P < 0.001), whereas the Europeans had higher prevalence of type 0 BAV (two commissures, no raphe) than Asians (14.5% vs. 6.8%, respectively; P < 0.001). The prevalence of moderate and severe aortic regurgitation was higher in Europeans than Asians (44.2% vs. 26.8%, respectively; P < 0.001) whereas there were no differences in BAV with normal function or aortic stenosis. After adjusting for demographics, comorbidities, and valve function, the dimensions of the aortic annulus [mean difference 1.17 mm/m2, 95% confidence interval (CI) 0.96-1.39], SOV (mean difference 1.86 mm/m2, 95% CI 1.47-2.24), STJ (mean difference 0.52 mm/m2, 95% CI 0.14-0.90) and AA (mean difference 1.05 mm/m2, 95% CI 0.57-1.52) were significantly larger among Asians compared with Europeans. This large multicentre registry reports for the first time that Asians with BAV showed more frequently type 1 BAV (with fusion between right and non-coronary cusp) and have larger aortic dimensions than Europeans. These findings have important implications for prosthesis type and size selection for TAVR.

CT predictors of post-procedural aortic regurgitation in patients referred for transcatheter aortic valve implantation: an analysis of 105 patients.

PubMed

Marwan, Mohamed; Achenbach, Stephan; Ensminger, Stefan M; Pflederer, Tobias; Ropers, Dieter; Ludwig, Josef; Weyand, Michael; Daniel, Werner G; Arnold, Martin

2013-06-01

Cardiac computed tomography (CT) allows accurate and detailed analysis of the anatomy of the aortic root and valve, including quantification of calcium. We evaluated the correlation between different CT parameters and the degree of post-procedural aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) using the balloon-expandable Edwards Sapien prosthesis. Pre-intervention contrast-enhanced dual source CT data sets of 105 consecutive patients (48 males, mean age 81 ± 6 years, mean logEuroSCORE 34 ± 13%) with symptomatic severe aortic valve stenosis referred for TAVI using the Edwards Sapien prosthesis (Edwards lifesciences, Inc., CA, USA) were analysed. The degrees of aortic valve commissural calcification and annular calcification were visually assessed on a scale from 0 to 3. Furthermore, the degree of aortic valve calcification as quantified by the Agatston score, aortic annulus eccentricity, aortic diameter at the level of the sinus of valsalva and at the sinotubular junction were assessed. Early post-procedural AR was assessed using aortography. Significant AR was defined as angiographic AR of at least moderate degree (AR ≥ 2). Visual assessment of the degree of aortic annular calcification as well as the Agatston score of aortic valve calcium correlated weakly, yet significantly with the degree of post-procedural AR (r = 0.31 and 0.24, p = 0.001 and 0.013, respectively). Compared to patients with AR < 2, patients with AR ≥ 2 showed more severe calcification of the aortic annulus (mean visual scores 1.9 ± 0.6 vs. 1.5 ± 0.6, p = 0.003) as well as higher aortic valve Agatston scores (1,517 ± 861 vs. 1,062 ± 688, p = 0.005). Visual score for commissural calcification did not differ significantly between both groups (mean scores 2.4 ± 0.5 vs. 2.5 ± 0.5, respectively, p = 0.117). No significant correlation was observed between the degree of AR and commissural calcification, aortic annulus eccentricity index or aortic diameters. The extent of aortic valve annular calcification, but not of commissural calcification, predicts significant post-procedural AR in patients referred for TAVI using the balloon-expandable Edwards Sapiens prosthesis.

Comparison of neuromuscular development in two dinophilid species (Annelida) suggests progenetic origin of Dinophilus gyrociliatus.

PubMed

Kerbl, Alexandra; Fofanova, Elizaveta G; Mayorova, Tatiana D; Voronezhskaya, Elena E; Worsaae, Katrine

2016-01-01

Several independent meiofaunal lineages are suggested to have originated through progenesis, however, morphological support for this heterochronous process is still lacking. Progenesis is defined as an arrest of somatic development (synchronously in various organ systems) due to early maturation, resulting in adults resembling larvae or juveniles of the ancestors. Accordingly, we established a detailed neuromuscular developmental atlas of two closely related Dinophilidae using immunohistochemistry and CLSM. This allows us to test for progenesis, questioning whether i) the adult smaller, dimorphic Dinophilus gyrociliatus resembles a younger developmental stage of the larger, monomorphic D. taeniatus and whether ii) dwarf males of D. gyrociliatus resemble an early developmental stage of D. gyrociliatus females. Both species form longitudinal muscle bundles first, followed by circular muscles, creating a grid of body wall musculature, which is the densest in adult D. taeniatus , while the architecture in adult female D. gyrociliatus resembles that of prehatching D. taeniatus . Both species display a subepidermal ganglionated nervous system with an anterior dorsal brain and five longitudinal ventral nerve bundles with six sets of segmental commissures (associated with paired ganglia). Neural differentiation of D. taeniatus and female D. gyrociliatus commissures occurs before hatching: both species start out forming one transverse neurite bundle per segment, which are thereafter joined by additional thin bundles. Whereas D. gyrociliatus arrests its development at this stage, adult D. taeniatus condenses the thin commissures again into one thick commissural bundle per segment. Generally, D. taeniatus adults demonstrate a seemingly more organized (= segmental) pattern of serotonin-like and FMRFamide-like immunoreactive elements. The dwarf male of D. gyrociliatus displays a highly aberrant neuromuscular system, showing no close resemblance to any early developmental stage of female Dinophilus , although the onset of muscular development mirrors the early myogenesis in females. The apparent synchronous arrest of nervous and muscular development in adult female D. gyrociliatus, resembling the prehatching stage of D. taeniatus, suggests that D. gyrociliatus have originated through progenesis. The synchrony in arrest of three organ systems, which show opposing reduction and addition of elements, presents one of the morphologically best-argued cases of progenesis within Spiralia.

Contralateral Effects and Binaural Interactions in Dorsal Cochlear Nucleus

PubMed Central

2005-01-01

The dorsal cochlear nucleus (DCN) receives afferent input from the auditory nerve and is thus usually thought of as a monaural nucleus, but it also receives inputs from the contralateral cochlear nucleus as well as descending projections from binaural nuclei. Evidence suggests that some of these commissural and efferent projections are excitatory, whereas others are inhibitory. The goals of this study were to investigate the nature and effects of these inputs in the DCN by measuring DCN principal cell (type IV unit) responses to a variety of contralateral monaural and binaural stimuli. As expected, the results of contralateral stimulation demonstrate a mixture of excitatory and inhibitory influences, although inhibitory effects predominate. Most type IV units are weakly, if at all, inhibited by tones but are strongly inhibited by broadband noise (BBN). The inhibition evoked by BBN is also low threshold and short latency. This inhibition is abolished and excitation is revealed when strychnine, a glycine-receptor antagonist, is applied to the DCN; application of bicuculline, a GABAA-receptor antagonist, has similar effects but does not block the onset of inhibition. Manipulations of discrete fiber bundles suggest that the inhibitory, but not excitatory, inputs to DCN principal cells enter the DCN via its output pathway, and that the short latency inhibition is carried by commissural axons. Consistent with their respective monaural effects, responses to binaural tones as a function of interaural level difference are essentially the same as responses to ipsilateral tones, whereas binaural BBN responses decrease with increasing contralateral level. In comparison to monaural responses, binaural responses to virtual space stimuli show enhanced sensitivity to the elevation of a sound source in ipsilateral space but reduced sensitivity in contralateral space. These results show that the contralateral inputs to the DCN are functionally relevant in natural listening conditions, and that one role of these inputs is to enhance DCN processing of spectral sound localization cues produced by the pinna. PMID:16075189

Deactivation of the inferior colliculus by cooling demonstrates intercollicular modulation of neuronal activity

PubMed Central

Orton, Llwyd D.; Poon, Paul W. F.; Rees, Adrian

2012-01-01

The auditory pathways coursing through the brainstem are organized bilaterally in mirror image about the midline and at several levels the two sides are interconnected. One of the most prominent points of interconnection is the commissure of the inferior colliculus (CoIC). Anatomical studies have revealed that these fibers make reciprocal connections which follow the tonotopic organization of the inferior colliculus (IC), and that the commissure contains both excitatory and, albeit fewer, inhibitory fibers. The role of these connections in sound processing is largely unknown. Here we describe a method to address this question in the anaesthetized guinea pig. We used a cryoloop placed on one IC to produce reversible deactivation while recording electrophysiological responses to sounds in both ICs. We recorded single units, multi-unit clusters and local field potentials (LFPs) before, during and after cooling. The degree and spread of cooling was measured with a thermocouple placed in the IC and other auditory structures. Cooling sufficient to eliminate firing was restricted to the IC contacted by the cryoloop. The temperature of other auditory brainstem structures, including the contralateral IC and the cochlea were minimally affected. Cooling below 20°C reduced or eliminated the firing of action potentials in frequency laminae at depths corresponding to characteristic frequencies up to ~8 kHz. Modulation of neural activity also occurred in the un-cooled IC with changes in single unit firing and LFPs. Components of LFPs signaling lemniscal afferent input to the IC showed little change in amplitude or latency with cooling, whereas the later components, which likely reflect inter- and intra-collicular processing, showed marked changes in form and amplitude. We conclude that the cryoloop is an effective method of selectively deactivating one IC in guinea pig, and demonstrate that auditory processing in the IC is strongly influenced by the other. PMID:23248587

[Functional anatomy of the cochlear nerve and the central auditory system].

PubMed

Simon, E; Perrot, X; Mertens, P

2009-04-01

The auditory pathways are a system of afferent fibers (through the cochlear nerve) and efferent fibers (through the vestibular nerve), which are not limited to a simple information transmitting system but create a veritable integration of the sound stimulus at the different levels, by analyzing its three fundamental elements: frequency (pitch), intensity, and spatial localization of the sound source. From the cochlea to the primary auditory cortex, the auditory fibers are organized anatomically in relation to the characteristic frequency of the sound signal that they transmit (tonotopy). Coding the intensity of the sound signal is based on temporal recruitment (the number of action potentials) and spatial recruitment (the number of inner hair cells recruited near the cell of the frequency that is characteristic of the stimulus). Because of binaural hearing, commissural pathways at each level of the auditory system and integration of the phase shift and the difference in intensity between signals coming from both ears, spatial localization of the sound source is possible. Finally, through the efferent fibers in the vestibular nerve, higher centers exercise control over the activity of the cochlea and adjust the peripheral hearing organ to external sound conditions, thus protecting the auditory system or increasing sensitivity by the attention given to the signal.

Termination of supraspinal descending pathways in the spinal cord of the tegu lizard, Tupinambis nigropunctatus.

PubMed

Cruce, W L

1975-01-01

Descending fiber projections to the lizard spinal cord were studied using anterograde axonal degeneration. Following hemisection of the cord at the first spinal segment, degeneration was found in the white and gray matter as far down as the 31st (caudal) segment. Degenerating fibers in the white matter were confined to the ipsilateral side and were found in the medial longitudinal fasiculus and the outer half ot the lateral and ventral funiculi. Degeneration was more intense in the dorsolateral and ventromedial funiculi than in the ventrolateral funiculus. In the gray matter, REXED's criteria were applied to Nissl-stained material to delimit boundaries of ten laminae. Degeneration of suprospinal axons was most intense in the medial part of VII, dorsal and ventral commissures to ramify contralaterally in the medial part of VII, in VII, and in medial IX. No degeneration was present in the lateral part of the spinal gray on the contralateral side. In Golgi-stained material, dendrites of lateral IX cells were seen to extend into lamina VII, the dorsolateral part of VII, and the lateral funiculus. Thus, fibers of the ventromedial supraspinal pathway may make axodendritic contact with motoneurons of lateral IX as well as medial IX, ipsilaterally. In addition, there is a possibility of a crossed connection to contralateral motoneurons.

Effects of failure of development of crossing brainstem pathways on ocular motor control.

PubMed

Jen, Joanna C

2008-01-01

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare, inherited disorder characterized by a congenital absence of conjugate horizontal eye movement with progressive scoliosis developing in childhood in patients who are otherwise neurologically intact. Detailed structural neuroimaging studies demonstrated abducens nerves and the absence of fibrosis in the extraocular muscles, and a remarkably dysmorphic hindbrain, with hypoplasia and flattened, butterfly-like medulla with deep midline cleft. Diffusion tensor imaging further demonstrated a widespread lack of crossing fibres in the brainstem, supported by evoked potential studies showing uncrossed descending motor and ascending sensory pathways in HGPPS patients. In these patients, we identified homozygous or compound heterozygous mutations in a gene we named ROBO3, which shares homology with evolutionarily conserved roundabout genes that are important in neural and vascular wiring. Removal of Robo3 in mice led to the absence of commissural crossing throughout the spinal cord and hindbrain (and death soon after birth). Therefore, ROBO3 is required for hindbrain axon midline crossing and morphogenesis in both human and mouse. We continue to investigate how ROBO3 mutations lead to massive miswiring in the hindbrain and disruption of conjugate horizontal gaze. Elucidation of the full extent of the anatomical abnormalities in HGPPS awaits improved neuroimaging techniques and detailed pathological studies.

Which Factors Affect Dental Esthetics and Smile Attractiveness in Orthodontically Treated Patients?

PubMed

Ahrari, Farzaneh; Heravi, Farzin; Rashed, Roozbeh; Zarrabi, Mohammad Javad; Setayesh, Yasin

2015-07-01

This study aimed to find the factors that affect dental esthetics and smile attractiveness in orthodontically treated patients according to laypeople's judgment, and to determine whether there is any relationship between dental and smile esthetics. Using the Q-sort technique, 60 laypersons (30 males, 30 females) rated dental and smile photographs of 48 orthodontically treated patients based on their degree of attractiveness. Dental and smile parameters of each rated image were measured by Smile Analyzer software. The Student's t-test and chi-square test were used to compare dental and smile parameters between attractive and unattractive images. The logistic regression was used to assess which variables predicted dental and smile esthetics in treated individuals. The philtral to commissural height ratio and gingival display were significantly different in attractive and unattractive smiles (P=0.003 and P=0.02, respectively). None of the dental variables were found to be a determinant of dental esthetics at the end of the orthodontic treatment (P>0.05). According to the judgment of all raters (female and male) and the male raters' judgment, smile attractiveness could be predicted by philtral to commissural height ratio and buccal corridor ratio (P<0.05). There was no statistically significant relationship between dental esthetics and smile attractiveness in orthodontically treated patients (P>0.05). The philtral to commissural height ratio and buccal corridor ratio can be considered as predictors of smile attractiveness in orthodontically treated patients. Achieving dental esthetics at the end of orthodontic treatment does not guarantee smile attractiveness.

Two-year quality of life after free flap reconstruction in tumor-site discrepancy among Taiwanese with moderately advanced oral squamous cell carcinoma.

PubMed

Chang, Kao-Ping; Lai, Chung-Sheng; Hsieh, Tung-Ying; Wu, Yi-Chia; Chang, Chih-Hau

2012-07-13

This study describes 2-year impact on quality of life (QOL) in relation to the anatomical discrepancy among T4a oral cancer patients after free flap reconstruction in Taiwan. Thirty-two patients who underwent tumor ablation with simultaneous microvascular free flap transfer at 2-year follow-up were recruited. They were divided into six subgroups, according to the resected area, consisting of: (1) buccal/retromolar trigone; (2) cheek; (3) commissure; (4) lip; (5) mandible; and (6) tongue. Functional disturbances and daily activity were analyzed using the Version-1 UW QOL Questionnaire with one more specific category: 'Drooling'. Kruskal-Wallis rank sums analysis was used to test differences in average QOL scores between these subgroups. Post-hoc analysis was applied to assess influence of dominant categories between subgroups. The category 'Pain' revealed the highest average score and reached significant statistical difference (P = 0.019) among all the categories, however, the category 'Employment' averaged the lowest score. Regarding 'Pain', there existed a statistical significance (P = 0.0032) between the commissure- and cheek-involved groups, which described the former showed poorer pain quality of life. The commissure-involved group had the lowest average score, which might imply the worst QOL in our study, especially for the categories 'Pain' and 'Drooling'. This present study of T4a patients was the first carried out in Taiwan implementing the QOL questionnaire, and its results may serve for future reference.

Heterogeneous patterns of oligodendroglial differentiation in the forebrain of the opossum Didelphis marsupialis.

PubMed

Barradas, P C; Gomes, S S; Cavalcante, L A

1998-01-01

The differentiation of oligodendrocytes in the forebrain of the opossum (Didelphis marsupialis) has been studied by the immunohistochemical identification of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and by the autoradiographic detection of the uptake of 3H-thymidine. CNPase is expressed early in oligodendroglia somata and fibre sheaths (myelin) in the forebrain and its persistence in the cell bodies is regionally heterogeneous, being ephemeral in cells within the optic pathway, supraoptic decussation, and posterior commissure, of intermediate duration in the mamillo-thalamic fascicle, and stria medullaris, and long-lasting in other diencephalic and in telencephalic tracts. In the cerebral cortex, most CNPase+ cells have small somata and multiple processes (types I and II). CNPase-expressing oligodendrocytes are also regionally heterogeneous in terms of proliferative capability, which could not be detected in forebrain tracts or diencephalon, but has appeared in a small proportion of cells in the neocortical white matter and in the fimbria. Our findings provide additional evidence in favour of the heterogeneity of oligodendrocytes.

Neurochemical phenotype of corticocortical connections in the macaque monkey: quantitative analysis of a subset of neurofilament protein-immunoreactive projection neurons in frontal, parietal, temporal, and cingulate cortices

NASA Technical Reports Server (NTRS)

Hof, P. R.; Nimchinsky, E. A.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

1995-01-01

The neurochemical characteristics of the neuronal subsets that furnish different types of corticocortical connections have been only partially determined. In recent years, several cytoskeletal proteins have emerged as reliable markers to distinguish subsets of pyramidal neurons in the cerebral cortex of primates. In particular, previous studies using an antibody to nonphosphorylated neurofilament protein (SMI-32) have revealed a consistent degree of regional and laminar specificity in the distribution of a subpopulation of pyramidal cells in the primate cerebral cortex. The density of neurofilament protein-immunoreactive neurons was shown to vary across corticocortical pathways in macaque monkeys. In the present study, we have used the antibody SMI-32 to examine further and to quantify the distribution of a subset of corticocortically projecting neurons in a series of long ipsilateral corticocortical pathways in comparison to short corticocortical, commissural, and limbic connections. The results demonstrate that the long association pathways interconnecting the frontal, parietal, and temporal neocortex have a high representation of neurofilament protein-enriched pyramidal neurons (45-90%), whereas short corticocortical, callosal, and limbic pathways are characterized by much lower numbers of such neurons (4-35%). These data suggest that different types of corticocortical connections have differential representation of highly specific neuronal subsets that share common neurochemical characteristics, thereby determining regional and laminar cortical patterns of morphological and molecular heterogeneity. These differences in neuronal neurochemical phenotype among corticocortical circuits may have considerable influence on cortical processing and may be directly related to the type of integrative function subserved by each cortical pathway. Finally, it is worth noting that neurofilament protein-immunoreactive neurons are dramatically affected in the course of Alzheimer's disease. The present results support the hypothesis that neurofilament protein may be crucially linked to the development of selective neuronal vulnerability and subsequent disruption of corticocortical pathways that lead to the severe impairment of cognitive function commonly observed in age-related dementing disorders.

Neurophysiological modification of CA1 pyramidal neurons in a transgenic mouse expressing a truncated form of disrupted-in-schizophrenia 1

PubMed Central

Booth, Clair A; Brown, Jonathan T; Randall, Andrew D

2014-01-01

A t(1;11) balanced chromosomal translocation transects the Disc1 gene in a large Scottish family and produces genome-wide linkage to schizophrenia and recurrent major depressive disorder. This study describes our in vitro investigations into neurophysiological function in hippocampal area CA1 of a transgenic mouse (DISC1tr) that expresses a truncated version of DISC1 designed to reproduce aspects of the genetic situation in the Scottish t(1;11) pedigree. We employed both patch-clamp and extracellular recording methods in vitro to compare intrinsic properties and synaptic function and plasticity between DISC1tr animals and wild-type littermates. Patch-clamp analysis of CA1 pyramidal neurons (CA1-PNs) revealed no genotype dependence in multiple subthreshold parameters, including resting potential, input resistance, hyperpolarization-activated ‘sag’ and resonance properties. Suprathreshold stimuli revealed no alteration to action potential (AP) waveform, although the initial rate of AP production was higher in DISC1tr mice. No difference was observed in afterhyperpolarizing potentials following trains of 5–25 APs at 50 Hz. Patch-clamp analysis of synaptic responses in the Schaffer collateral commissural (SC) pathway indicated no genotype-dependence of paired pulse facilitation, excitatory postsynaptic potential summation or AMPA/NMDA ratio. Extracellular recordings also revealed an absence of changes to SC synaptic responses and indicated input–output and short-term plasticity were also unaltered in the temporoammonic (TA) input. However, in DISC1tr mice theta burst-induced long-term potentiation was enhanced in the SC pathway but completely lost in the TA pathway. These data demonstrate that expressing a truncated form of DISC1 affects intrinsic properties of CA1-PNs and produces pathway-specific effects on long-term synaptic plasticity. PMID:24712988

Which Factors Affect Dental Esthetics and Smile Attractiveness in Orthodontically Treated Patients?

PubMed Central

Heravi, Farzin; Rashed, Roozbeh; Zarrabi, Mohammad Javad; Setayesh, Yasin

2015-01-01

Objectives: This study aimed to find the factors that affect dental esthetics and smile attractiveness in orthodontically treated patients according to laypeople’s judgment, and to determine whether there is any relationship between dental and smile esthetics. Materials and Methods: Using the Q-sort technique, 60 laypersons (30 males, 30 females) rated dental and smile photographs of 48 orthodontically treated patients based on their degree of attractiveness. Dental and smile parameters of each rated image were measured by Smile Analyzer software. The Student’s t-test and chi-square test were used to compare dental and smile parameters between attractive and unattractive images. The logistic regression was used to assess which variables predicted dental and smile esthetics in treated individuals. Results: The philtral to commissural height ratio and gingival display were significantly different in attractive and unattractive smiles (P=0.003 and P=0.02, respectively). None of the dental variables were found to be a determinant of dental esthetics at the end of the orthodontic treatment (P>0.05). According to the judgment of all raters (female and male) and the male raters’ judgment, smile attractiveness could be predicted by philtral to commissural height ratio and buccal corridor ratio (P<0.05). There was no statistically significant relationship between dental esthetics and smile attractiveness in orthodontically treated patients (P>0.05). Conclusion: The philtral to commissural height ratio and buccal corridor ratio can be considered as predictors of smile attractiveness in orthodontically treated patients. Achieving dental esthetics at the end of orthodontic treatment does not guarantee smile attractiveness. PMID:26877739

Canine oral mucosa evaluation as a potential autograft tissue for the treatment of unresponsive keratoconjunctivitis sicca.

PubMed

Cherry, Rose L; Smith, Jodi D; Ben-Shlomo, Gil

2018-01-01

Labial mucosa transplantation for the treatment of canine keratoconjunctivitis sicca (KCS) has been reported recently. Postoperative alleviation of clinical signs was noted and assumed to be the result of labial salivary glands providing lubrication to the ocular tissue. The aim of this study was to evaluate the presence of minor salivary glands (MSG) in the canine oral mucosa. Oral mucosal biopsies were collected from six dogs that died (n = 1) or were euthanized (n = 5) for reasons unrelated to this study. The breeds included were two Doberman Pinschers, one Labrador Retriever, one Portuguese Water Dog, one German Shepherd Dog, and one mixed canine. Three were spayed females, and three were castrated males with the median age of 9 years (range, 6-13 years). Samples were obtained by an 8-mm punch biopsy at the following locations of the canine oral cavity: upper rostral labial mucosa at midline, lower rostral labial mucosa at midline, upper labial mucosa near the commissure, lower labial mucosa near the commissure, and buccal mucosa approximately 1 cm caudal to the commissure. Samples were routinely processed with hematoxylin and eosin, and periodic acid-Schiff stains. Samples were evaluated by light microscopy. At the selected locations, no MSG or other secreting cells were detected. Minor salivary glands are not associated with alleviation of canine KCS symptoms following labial mucosa transplantation. Further studies are needed to determine the mechanism leading to the transient improvement of KCS symptoms in canine patients following labial mucosa transplantation. © 2017 American College of Veterinary Ophthalmologists.

Magnetic resonance findings of the corpus callosum in canine and feline lysosomal storage diseases.

PubMed

Hasegawa, Daisuke; Tamura, Shinji; Nakamoto, Yuya; Matsuki, Naoaki; Takahashi, Kimimasa; Fujita, Michio; Uchida, Kazuyuki; Yamato, Osamu

2013-01-01

Several reports have described magnetic resonance (MR) findings in canine and feline lysosomal storage diseases such as gangliosidoses and neuronal ceroid lipofuscinosis. Although most of those studies described the signal intensities of white matter in the cerebrum, findings of the corpus callosum were not described in detail. A retrospective study was conducted on MR findings of the corpus callosum as well as the rostral commissure and the fornix in 18 cases of canine and feline lysosomal storage diseases. This included 6 Shiba Inu dogs and 2 domestic shorthair cats with GM1 gangliosidosis; 2 domestic shorthair cats, 2 familial toy poodles, and a golden retriever with GM2 gangliosidosis; and 2 border collies and 3 chihuahuas with neuronal ceroid lipofuscinoses, to determine whether changes of the corpus callosum is an imaging indicator of those diseases. The corpus callosum and the rostral commissure were difficult to recognize in all cases of juvenile-onset gangliosidoses (GM1 gangliosidosis in Shiba Inu dogs and domestic shorthair cats and GM2 gangliosidosis in domestic shorthair cats) and GM2 gangliosidosis in toy poodles with late juvenile-onset. In contrast, the corpus callosum and the rostral commissure were confirmed in cases of GM2 gangliosidosis in a golden retriever and canine neuronal ceroid lipofuscinoses with late juvenile- to early adult-onset, but were extremely thin. Abnormal findings of the corpus callosum on midline sagittal images may be a useful imaging indicator for suspecting lysosomal storage diseases, especially hypoplasia (underdevelopment) of the corpus callosum in juvenile-onset gangliosidoses.

Magnetic Resonance Findings of the Corpus Callosum in Canine and Feline Lysosomal Storage Diseases

PubMed Central

Hasegawa, Daisuke; Tamura, Shinji; Nakamoto, Yuya; Matsuki, Naoaki; Takahashi, Kimimasa; Fujita, Michio; Uchida, Kazuyuki; Yamato, Osamu

2013-01-01

Several reports have described magnetic resonance (MR) findings in canine and feline lysosomal storage diseases such as gangliosidoses and neuronal ceroid lipofuscinosis. Although most of those studies described the signal intensities of white matter in the cerebrum, findings of the corpus callosum were not described in detail. A retrospective study was conducted on MR findings of the corpus callosum as well as the rostral commissure and the fornix in 18 cases of canine and feline lysosomal storage diseases. This included 6 Shiba Inu dogs and 2 domestic shorthair cats with GM1 gangliosidosis; 2 domestic shorthair cats, 2 familial toy poodles, and a golden retriever with GM2 gangliosidosis; and 2 border collies and 3 chihuahuas with neuronal ceroid lipofuscinoses, to determine whether changes of the corpus callosum is an imaging indicator of those diseases. The corpus callosum and the rostral commissure were difficult to recognize in all cases of juvenile-onset gangliosidoses (GM1 gangliosidosis in Shiba Inu dogs and domestic shorthair cats and GM2 gangliosidosis in domestic shorthair cats) and GM2 gangliosidosis in toy poodles with late juvenile-onset. In contrast, the corpus callosum and the rostral commissure were confirmed in cases of GM2 gangliosidosis in a golden retriever and canine neuronal ceroid lipofuscinoses with late juvenile- to early adult-onset, but were extremely thin. Abnormal findings of the corpus callosum on midline sagittal images may be a useful imaging indicator for suspecting lysosomal storage diseases, especially hypoplasia (underdevelopment) of the corpus callosum in juvenile-onset gangliosidoses. PMID:24386203

Two-year quality of life after free flap reconstruction in tumor-site discrepancy among Taiwanese with moderately advanced oral squamous cell carcinoma

PubMed Central

2012-01-01

Background This study describes 2-year impact on quality of life (QOL) in relation to the anatomical discrepancy among T4a oral cancer patients after free flap reconstruction in Taiwan. Methods Thirty-two patients who underwent tumor ablation with simultaneous microvascular free flap transfer at 2-year follow-up were recruited. They were divided into six subgroups, according to the resected area, consisting of: (1) buccal/retromolar trigone; (2) cheek; (3) commissure; (4) lip; (5) mandible; and (6) tongue. Functional disturbances and daily activity were analyzed using the Version-1 UW QOL Questionnaire with one more specific category: ‘Drooling’. Kruskal-Wallis rank sums analysis was used to test differences in average QOL scores between these subgroups. Post-hoc analysis was applied to assess influence of dominant categories between subgroups. Results The category ‘Pain’ revealed the highest average score and reached significant statistical difference (P = 0.019) among all the categories, however, the category ‘Employment’ averaged the lowest score. Regarding ‘Pain’, there existed a statistical significance (P = 0.0032) between the commissure- and cheek-involved groups, which described the former showed poorer pain quality of life. Conclusions The commissure-involved group had the lowest average score, which might imply the worst QOL in our study, especially for the categories ‘Pain’ and ‘Drooling’. This present study of T4a patients was the first carried out in Taiwan implementing the QOL questionnaire, and its results may serve for future reference. PMID:22789070

The Brain as "Sexual Organ."

ERIC Educational Resources Information Center

Science, 1991

1991-01-01

The body of data indicating sex differences in the brains of almost every mammalian family examined so far (rodents, birds, monkeys, and human beings) is reviewed. The differences in the hypothalamus, thalamus, corpus callosum, anterior commissure, and the hippocampus are described. (KR)

Treatment outcome and prognostic factor of CO2 laser cordectomy for early glottic cancer

NASA Astrophysics Data System (ADS)

Chung, Phil-Sang; Lee, Sang Joon

2012-02-01

Objectives: Laser cordectomy is very popular nowadays and become one of the treatments of choice for early glottis carcinoma. Transoral laser microsurgery has many advantages comparing conventional open surgery or radiation therapy. In this study, we examined the oncologic results of laser cordectomy for early glottic cancer and analyzed the prognostic impact on the survival of the several tumor-related and treatment-related factors. Methods: Patients who were diagnosed as early glottic squamous cell carcinoma, treated by laser cordectomy with curative intent were analyzed. Patients with preivous radiation therapy were included. From June 1988 to March 2005, 202 patients from five hospitals were analyzed (174 T1, 28 T2). Results: Five-year overall survival and disease-free survival were 98.4% and 84.9%. Twenty two patients developed local recurrence. Total laryngectomy was done in 6 patients and laryngeal preservation rate was 97%. Recurrence was higher in the patients with anterior commissure involvement (9/39) than without anterior commissure involvement (13/163). Recurrence was higher in T1b (4/15) than T1a (13/159). Previous radiation was also highly related to the recurrence (7/20 vs 15/182). Twenty patients with local recurrence after radiation therapy were treated by salvage laser cordectomy. Of them, 7 patients developed local recurrence and 5 year disease-free survival was 57%. Complication was rare with one case of hemorrhage. Tracheotomy was not necessary in all patients. Conclusions: Laser cordectomy for early glottic carcinoma showed high survival, laryngeal preservation rate and low complication rate. The prognostic factors were anterior commissure involvement, both vocal fold involvement and previous radiotherapy.

Analysis of dynamic smile and upper lip curvature in young Chinese

PubMed Central

Liang, Ling-Zhi; Hu, Wen-Jie; Zhang, Yan-Ling; Chung, Kwok-Hung

2013-01-01

During smile evaluation and anterior esthetic construction, the anatomic and racial variations should be considered in order to achieve better matching results. The aims of this study were to validate an objective method for recording spontaneous smile process and to categorize the smile and upper lip curvature of Chinese Han-nationality youth. One hundred and eighty-eight Chinese Han-nationality youths (88 males and 100 females) ranged from 20 to 35 years of age were selected. Spontaneous smiles were elicited by watching comical movies and the dynamics of the spontaneous smile were captured continuously with a digital video camera. All subjects' smiles were categorized into three types: commissure, cuspid and gummy smile based on video editing software and final images. Subjects' upper lip curvatures were also measured and divided into three groups: upward, straight and downward. Reliability analysis was conducted to obtain intra-rater reliabilities on twice measurements. The Pearson Chi-square test was used to compare differences for each parameters (α=0.05). In smile classification, 60.6% commissure smile, 33.5% cuspid smile and 5.9% gummy smile were obtained. In upper lip measurement, 26.1% upward, 39.9% straight and 34.0% downward upper lip curvature were determined. The commissure smile group showed statistically significant higher percentage of straight (46.5%) and upward (40.4%) in upper lip curvatures (P<0.05), while cuspid smile group (65.1%) and gummy smile group (72.7%) showed statistically significant higher frequency in downward upper lip curvature (P<0.05). It is evident that differences in upper lip curvature and smile classification exist based on race, when comparing Chinese subjects with those of Caucasian descent, and gender. PMID:23558343

The pedicled masseter muscle transfer for smile reconstruction in facial paralysis: repositioning the origin and insertion.

PubMed

Matic, Damir B; Yoo, John

2012-08-01

The pedicled masseter muscle transfer (PMMT) is introduced as a new reconstructive option for dynamic smile restoration in patients with facial paralysis. The masseter muscle is detached from both its origin and insertion and transferred to a new position to imitate the function of the native zygomaticus major muscle. Part one of this study consisted of cadaveric dissections of 4 heads (eight sides) in order to determine whether the masseter muscle could be (a) pedicled solely by its dominant neurovascular bundle and (b) repositioned directly over the native zygomaticus major. The second part of the study consisted of clinical assessments in three patients in order to confirm the applicability of this muscle transfer. Commissure excursion and vector of contraction following PMMT were compared to the non-paralyzed side. In all eight sides, the masseter muscles were successfully isolated on their pedicle and transposed on top of and in-line with the ipsilateral zygomaticus major. The mean length of the masseter and its angle from Frankfurt's horizontal line after transposition compared favorably to the native zygomaticus major muscle. In the clinical cases, the mean commissure movements of the paralyzed and normal sides were 7 mm and 12 mm respectively. The mean angles of commissural movement for the paralyzed and normal sides were 62° and 59° respectively. The PMMT can be used as a dynamic reconstruction for patients with permanent facial paralysis. As we gain experience with the PMMT, it may be possible to use it as a first-line option for patients not eligible for free micro-neurovascular reconstruction. Copyright © 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Neural connectivity of the anterior body of the fornix in the human brain: diffusion tensor imaging study.

PubMed

Jang, Sung Ho; Kwon, Hyeok Gyu

2014-01-24

A few studies have reported on the neural connectivity of the fornix in the human brain, however, little is known about the neural connectivity of the anterior body of the fornix. In this study, we used diffusion tensor imaging in investigation of the neural connectivity of the anterior body of the fornix in normal subjects. Forty healthy subjects were recruited for this study. A seed region of interest was placed on the anterior body of the fornix using the FMRIB Software Library. Connectivity was defined as the incidence of connection between the anterior body of the fornix and any neural structure of the brain at the threshold of 5, 25, and 50 streamlines. In all subjects, the anterior body of the fornix showed 100% connectivity to the anterior commissure and hypothalamus at thresholds of 5, 25, and 50. On the other hand, regarding the thresholds of 5, 25, and 50, the anterior body of the fornix showed connectivity to the septal forebrain region (53.8, 23.8, and 15.0%), frontal lobe via anterior commissure (41.3,12.5, and 10.0%), medial temporal lobe (85.0,66.3, and 62.5%), lateral temporal lobe (75.0, 56.3, and 35.0%), occipital lobe (21.3, 5.0, and 1.3%), frontal lobe via septum pellucidum (28.8, 13.8, and 8.8%), tegmentum of midbrain (7.5, 5.0, and 0%), tectum of midbrain (2.5,0, and 0%), and tegmentum of pons (5.0,0, and 0%). The anterior body of the fornix showed high connectivity with the anterior commissure and hypothalamus, and brain areas relevant to cholinergic nuclei (the septal forebrain region and brainstem) and memory function (the medial temporal lobe). Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Development and application of a perioral force measurement system for infants with cleft lip and palate.

PubMed

Zhang, Lixian; Zheng, Yaqi; Rong, Qiong; Wu, Guofeng

2017-11-01

Muscles converge or intertweave around the perioral area, and this can be treated with sequential therapy in infants with cleft lip and palate (CLP). The force of perioral muscles has a great influence on maxillary development and morphology. Perioral force in infants with CLP has not been well studied, and accurate and reliable measurement of perioral force in infants remains a challenge. This study aimed to investigate a new way to accurately and reliably measure perioral force in infants with unilateral CLP (UCLP) and explore the change before and after cheiloplasty. A perioral force measurement system was developed and applied to measure perioral force at labial frenum area and the commissures on both the normal and the cleft sides of four infants with UCLP before and after cheiloplasty. The results were analyzed using the SPSS 19.0 software. The perioral force measurement system appears to produce valid results in infants with UCLP. Before cheiloplasty, the perioral force of labial frenum area was 1.79 ± 0.94 g/cm 2 and that of commissure on the normal and cleft sides was 5.41 ± 1.01 g/cm 2 and 3.12 ± 1.55 g/cm 2 , respectively (P < 0.05). After cheiloplasty, perioral force of labial frenum area was 12.73 ± 3.51 g/cm 2 and that of commissure on the normal and cleft sides was 7.64 ± 1.64 g/cm 2 and 7.27 ± 1.89 g/cm 2 , respectively (P > 0.05). Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Mitral valve morphology assessed by three-dimensional transthoracic echocardiography in healthy dogs and dogs with myxomatous mitral valve disease.

PubMed

Menciotti, G; Borgarelli, M; Aherne, M; Wesselowski, S; Häggström, J; Ljungvall, I; Lahmers, S M; Abbott, J A

2017-04-01

To assess differences in morphology of the mitral valve (MV) between healthy dogs and dogs affected by myxomatous mitral valve disease (MMVD) using real-time transthoracic three-dimensional echocardiography (RT3DE). Thirty-four were normal dogs and 79 dogs were affected by MMVD. Real-time transthoracic three-dimensional echocardiography mitral datasets were digitally recorded and analyzed using dedicated software. The following variables were obtained and compared between healthy dogs and dogs with MMVD at different stages: antero-posterior annulus diameter, anterolateral-posteromedial annulus diameter, commissural diameter, annulus height, annulus circumference, annulus area, anterior leaflet length, anterior leaflet area, posterior leaflet length, posterior leaflet area, non-planar angle, annulus sphericity index, tenting height, tenting area, tenting volume, the ratio of annulus height and commissural diameter. Dogs with MMVD had a more circular MV annulus compared to healthy dogs as demonstrated by an increased annulus sphericity index (p=0.0179). Affected dogs had a less saddle-shaped MV manifest as a decreased annulus height to commissural width ratio (p=0.0004). Tenting height (p<0.0001), area (p<0.0001), and volume (p<0.0001) were less in affected dogs. Real-time transthoracic three-dimensional echocardiography analysis demonstrated that dogs affected by MMVD had a more circular and less saddle-shaped MV annulus, as well as reduced tenting height area and volume, compared to healthy dogs. Multiple variables differed between dogs at different stages of MMVD. Diagnostic and prognostic utility of these variables, and the significance of these changes in the pathogenesis and natural history of MMVD, require further attention. Copyright © 2017 Elsevier B.V. All rights reserved.

Structural-Functional Properties of Identified Excitatory and Inhibitory Interneurons within Pre-Bötzinger Complex Respiratory Microcircuits

PubMed Central

Koizumi, Hidehiko; Koshiya, Naohiro; Chia, Justine X.; Cao, Fang; Nugent, Joseph; Zhang, Ruli

2013-01-01

We comparatively analyzed cellular and circuit properties of identified rhythmic excitatory and inhibitory interneurons within respiratory microcircuits of the neonatal rodent pre-Bötzinger complex (pre-BötC), the structure generating inspiratory rhythm in the brainstem. We combined high-resolution structural–functional imaging, molecular assays for neurotransmitter phenotype identification in conjunction with electrophysiological property phenotyping, and morphological reconstruction of interneurons in neonatal rat and mouse slices in vitro. This approach revealed previously undifferentiated structural–functional features that distinguish excitatory and inhibitory interneuronal populations. We identified distinct subpopulations of pre-BötC glutamatergic, glycinergic, GABAergic, and glycine-GABA coexpressing interneurons. Most commissural pre-BötC inspiratory interneurons were glutamatergic, with a substantial subset exhibiting intrinsic oscillatory bursting properties. Commissural excitatory interneurons projected with nearly planar trajectories to the contralateral pre-BötC, many also with axon collaterals to areas containing inspiratory hypoglossal (XII) premotoneurons and motoneurons. Inhibitory neurons as characterized in the present study did not exhibit intrinsic oscillatory bursting properties, but were electrophysiologically distinguished by more pronounced spike frequency adaptation properties. Axons of many inhibitory neurons projected ipsilaterally also to regions containing inspiratory XII premotoneurons and motoneurons, whereas a minority of inhibitory neurons had commissural axonal projections. Dendrites of both excitatory and inhibitory interneurons were arborized asymmetrically, primarily in the coronal plane. The dendritic fields of inhibitory neurons were more spatially compact than those of excitatory interneurons. Our results are consistent with the concepts of a compartmental circuit organization, a bilaterally coupled excitatory rhythmogenic kernel, and a role of pre-BötC inhibitory neurons in shaping inspiratory pattern as well as coordinating inspiratory and expiratory activity. PMID:23407957

Contributions to Clinical Neuropsychology.

ERIC Educational Resources Information Center

Benton, Arthur L., Ed.

Seven aspects of neuropsychology are discussed including modern trends in neuropsychology by Klaus Poeck, the behavioral effect s of commissural section by George Ettlinger and Colin B. Blakemore, neuropsychological studies of phantom limbs by Sidney Weinstein, and problems in the anatomical understanding of aphasias by Norman Geschwind. Also…

Transoral Laser Microsurgery in Early Glottic Lesions.

PubMed

Sjögren, E V

2017-01-01

To give an overview of the evolvement of transoral laser microsurgery (TLM) in the treatment of early glottic carcinoma and highlight the contribution of recent literature. The indications and limits of TLM have been well specified. Effects on swallowing have been well documented. Introduction of narrow-band imaging (NBI) and diffusion-weighted magnetic resonance has been shown of additional value for outcome. The first reports on transoral robotic surgery show that it may be of added value in the future. TLM for early glottic carcinoma (Tis-T2) has very good oncological outcomes with indications of higher larynx preservation in TLM than that in radiotherapy. The anterior commissure is a risk factor if involved in the cranio-caudal plane, and reduced vocal fold mobility is a risk factor when this is due to arytenoid involvement. The best voice results are achieved when the anterior commissure can be left intact along with part of the vocal fold muscle although even in larger resections, patient self-reported voice handicap is still limited.

A Proposal of New Reference System for the Standard Axial, Sagittal, Coronal Planes of Brain Based on the Serially-Sectioned Images

PubMed Central

Park, Jin Seo; Park, Hyo Seok; Shin, Dong Sun; Har, Dong-Hwan; Cho, Zang-Hee; Kim, Young-Bo; Han, Jae-Yong; Chi, Je-Geun

2010-01-01

Sectional anatomy of human brain is useful to examine the diseased brain as well as normal brain. However, intracerebral reference points for the axial, sagittal, and coronal planes of brain have not been standardized in anatomical sections or radiological images. We made 2,343 serially-sectioned images of a cadaver head with 0.1 mm intervals, 0.1 mm pixel size, and 48 bit color and obtained axial, sagittal, and coronal images based on the proposed reference system. This reference system consists of one principal reference point and two ancillary reference points. The two ancillary reference points are the anterior commissure and the posterior commissure. And the principal reference point is the midpoint of two ancillary reference points. It resides in the center of whole brain. From the principal reference point, Cartesian coordinate of x, y, z could be made to be the standard axial, sagittal, and coronal planes. PMID:20052359

Glutamatergic Receptor Activation in the Commisural Nucleus Tractus Solitarii (cNTS) Mediates Brain Glucose Retention (BGR) Response to Anoxic Carotid Chemoreceptor (CChr) Stimulation in Rats.

PubMed

Cuéllar, R; Montero, S; Luquín, S; García-Estrada, J; Dobrovinskaya, O; Melnikov, V; Lemus, M; de Álvarez-Buylla, E Roces

2015-01-01

Glutamate, released from central terminals of glossopharyngeal nerve, is a major excitatory neurotransmitter of commissural nucleus tractus solitarii (cNTS) afferent terminals, and brain derived neurotrophic factor (BDNF) has been shown to attenuate glutamatergic AMPA currents in NTS neurons. To test the hypothesis that AMPA contributes to glucose regulation in vivo modulating the hyperglycemic reflex with brain glucose retention (BGR), we microinjected AMPA and NBQX (AMPA antagonist) into the cNTS before carotid chemoreceptor stimulation in anesthetized normal Wistar rats, while hyperglycemic reflex an brain glucose retention (BGR) were analyzed. To investigate the underlying mechanisms, GluR2/3 receptor and c-Fos protein expressions in cNTS neurons were determined. We showed that AMPA in the cNTS before CChr stimulation inhibited BGR observed in aCSF group. In contrast, NBQX in similar conditions, did not modify the effects on glucose variables observed in aCSF control group. These experiments suggest that glutamatergic pathways, via AMPA receptors, in the cNTS may play a role in glucose homeostasis.

"Angular" plasma cell cheilitis.

PubMed

da Cunha Filho, Roberto Rheingantz; Tochetto, Lucas Baldissera; Tochetto, Bruno Baldissera; de Almeida, Hiram Larangeira; Lorencette, Nádia Aparecida; Netto, José Fillus

2014-03-17

Plasma cell cheilitis is an extremely rare disease, characterized by erythematous-violaceous, ulcerated and asymptomatic plaques, which evolve slowly. The histological characteristics include dermal infiltrate composed of mature plasmocytes. We report a case of Plasma cell angular cheilitis in a 58-year-old male, localized in the lateral oral commissure.

Development of serotonin-like immunoreactivity in the embryos and larvae of nudibranch mollusks with emphasis on the structure and possible function of the apical sensory organ.

PubMed

Kempf, S C; Page, L R; Pires, A

1997-09-29

This investigation provides a light and electron microscopic examination of the development of serotonin-like immunoreactivity and structure of the apical sensory organ (ASO) in embryos and/or larvae of four nudibranch species: Berghia verrucicornis, Phestilla sibogae, Melibe leonina, and Tritonia diomedea. Serotonin-like immunoreactivity is first expressed in somata, dendrites, and axons of a group of five distinct neurons within the ASO. These neurons extend axons into an apical neuropil, a structure that is situated centrally and immediately dorsal to the cerebral commissure. Three of these neurons possess sensory dendrites that extend through the pretrochal epithelium, each supporting two cilia at their distal ends. Later development of serotonin-like immunoreactivity includes 1) axons from the apical neuropil that extend into each of the velar lobes; 2) neuron perikarya in the cerebral and pedal ganglia; 3) axons that extend through the cerebral commissure, cerebral-pedal connectives, pedal commissure, and possibly the visceral loop connective; and 4) axons extending from each pedal ganglion into the larval foot. Ultrastructurally, the ASO can be seen to be composed of three lobes and an apical neuropil that is separately delineated from the cerebral commissure. Four cell types are present within the ASO: ciliary tuft cells, type I and type II parampullary neurons, and ampullary neurons. Immunofluorescence and 3,3' diaminobenzidine tetrahydrochloride (DAB) labeling verify that the serotonergic neurons of the ASO are type I and type II parampullary neurons. The ampullary and type I parampullary neurons possess dendrites that extend through the pretrochal epithelium. These dendrites are partitioned into three bundles, one on either side of the ciliary tuft cells and a third bundle penetrating the pretrochal epithelium centrally between the ciliary tuft cells. One serotonergic type I parampullary neuron is associated with each of these bundles. Two ampullary neurons are associated with each of the lateral dendritic bundles, while the central bundle includes only one. Ultrastructural analyses of serotonergic axonal innervation arising from the ASO agree with those determined from fluorescently labeled material. The structure of the ASO and its associated serotonergic axons suggest that the serotonergic component of this structure senses environmental stimuli affecting velar function, possibly the contractility of muscle fibers in the velar lobes. Similarities and differences among the ASOs of embryos and larvae from various invertebrate phyla may provide useful data that will assist in the reconstruction of phylogenetic relationships.

The occurrence of oral-mucosal lesions among employees of a steelmill--a preliminary study.

PubMed

Zain, R B; Koh, L S

1988-11-01

A study has been conducted on 198 employees of a steel-mill industry. These participants were examined for mucosal lesions in the oral cavity and including the commissures and vermillion borders of the lips. The prevalences of 16 types of lesions are reported.

Drosophila Neurexin IV Interacts with Roundabout and is Required for Repulsive Midline Axon Guidance

PubMed Central

Banerjee, Swati; Blauth, Kevin; Peters, Kimberly; Rogers, Stephen L.; Fanning, Alan S.; Bhat, Manzoor A.

2010-01-01

Slit/Roundabout (Robo) signaling controls midline repulsive axon guidance. However, proteins that interact with Slit/Robo at the cell surface remain largely uncharacterized. Here, we report that the Drosophila transmembrane septate junction-specific protein, Neurexin IV (Nrx IV), functions in midline repulsive axon guidance. Nrx IV is expressed in the neurons of the developing ventral nerve cord and nrx IV mutants show crossing and circling of ipsilateral axons and fused commissures. Interestingly, the axon guidance defects observed in nrx IV mutants seem independent of its other binding partners such as Contactin and Neuroglian and the midline glia protein Wrapper that interacts in trans with Nrx IV. nrx IV mutants show diffuse Robo localization and dose-dependent genetic interactions between nrx IV/robo and nrx IV/slit indicate that they function in a common pathway. In vivo biochemical studies reveal that Nrx IV associates with Robo, Slit and Syndecan, and interactions between Robo and Slit, or Nrx IV and Slit, are affected in nrx IV and robo mutants, respectively. Coexpression of Nrx IV and Robo in mammalian cells confirms that these proteins retain the ability to interact in a heterologous system. Furthermore, we demonstrate that the extracellular region of Nrx IV is sufficient to rescue Robo localization and axon guidance phenotypes in nrx IV mutants. Together our studies establish that Nrx IV is essential for proper Robo localization, and identify Nrx IV as a novel interacting partner of the Slit/Robo signaling pathway. PMID:20410118

Drosophila neurexin IV interacts with Roundabout and is required for repulsive midline axon guidance.

PubMed

Banerjee, Swati; Blauth, Kevin; Peters, Kimberly; Rogers, Stephen L; Fanning, Alan S; Bhat, Manzoor A

2010-04-21

Slit/Roundabout (Robo) signaling controls midline repulsive axon guidance. However, proteins that interact with Slit/Robo at the cell surface remain largely uncharacterized. Here, we report that the Drosophila transmembrane septate junction-specific protein Neurexin IV (Nrx IV) functions in midline repulsive axon guidance. Nrx IV is expressed in the neurons of the developing ventral nerve cord, and nrx IV mutants show crossing and circling of ipsilateral axons and fused commissures. Interestingly, the axon guidance defects observed in nrx IV mutants seem independent of its other binding partners, such as Contactin and Neuroglian and the midline glia protein Wrapper, which interacts in trans with Nrx IV. nrx IV mutants show diffuse Robo localization, and dose-dependent genetic interactions between nrx IV/robo and nrx IV/slit indicate that they function in a common pathway. In vivo biochemical studies reveal that Nrx IV associates with Robo, Slit, and Syndecan, and interactions between Robo and Slit, or Nrx IV and Slit, are affected in nrx IV and robo mutants, respectively. Coexpression of Nrx IV and Robo in mammalian cells confirms that these proteins retain the ability to interact in a heterologous system. Furthermore, we demonstrate that the extracellular region of Nrx IV is sufficient to rescue Robo localization and axon guidance phenotypes in nrx IV mutants. Together, our studies establish that Nrx IV is essential for proper Robo localization and identify Nrx IV as a novel interacting partner of the Slit/Robo signaling pathway.

Combining tract- and atlas-based analysis reveals microstructural abnormalities in early Tourette syndrome children.

PubMed

Wen, Hongwei; Liu, Yue; Wang, Jieqiong; Rekik, Islem; Zhang, Jishui; Zhang, Yue; Tian, Hongwei; Peng, Yun; He, Huiguang

2016-05-01

Tourette syndrome (TS) is a neurological disorder that causes uncontrolled repetitive motor and vocal tics in children. Examining the neural basis of TS churned out different research studies that advanced our understanding of the brain pathways involved in its development. Particularly, growing evidence points to abnormalities within the fronto-striato-thalamic pathways. In this study, we combined Tract-Based Spatial Statistics (TBSS) and Atlas-based regions of interest (ROI) analysis approach, to investigate the microstructural diffusion changes in both deep and superficial white matter (SWM) in TS children. We then characterized the altered microstructure of white matter in 27 TS children in comparison with 27 age- and gender-matched healthy controls. We found that fractional anisotropy (FA) decreases and radial diffusivity (RD) increases in deep white matter (DWM) tracts in cortico-striato-thalamo-cortical (CSTC) circuit as well as SWM. Furthermore, we found that lower FA values and higher RD values in white matter regions are correlated with more severe tics, but not tics duration. Besides, we also found both axial diffusivity and mean diffusivity increase using Atlas-based ROI analysis. Our work may suggest that microstructural diffusion changes in white matter is not only restricted to the gray matter of CSTC circuit but also affects SWM within the primary motor and somatosensory cortex, commissural and association fibers. Hum Brain Mapp 37:1903-1919, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Structural Changes after Videogame Practice Related to a Brain Network Associated with Intelligence

ERIC Educational Resources Information Center

Colom, Roberto; Quiroga, Ma. Angeles; Solana, Ana Beatriz; Burgaleta, Miguel; Roman, Francisco J.; Privado, Jesus; Escorial, Sergio; Martinez, Kenia; Alvarez-Linera, Juan; Alfayate, Eva; Garcia, Felipe; Lepage, Claude; Hernandez-Tamames, Juan Antonio; Karama, Sherif

2012-01-01

Here gray and white matter changes after four weeks of videogame practice were analyzed using optimized voxel-based morphometry (VBM), cortical surface and cortical thickness indices, and white matter integrity computed from several projection, commissural, and association tracts relevant to cognition. Beginning with a sample of one hundred young…

NO nerves in a tapeworm. NADPH-diaphorase histochemistry in adult Hymenolepis diminuta.

PubMed

Gustafsson, M K; Lindholm, A M; Terenina, N B; Reuter, M

1996-12-01

The free radical nitric oxide (NO), which is synthesized by nitric oxide synthase (NOS), has recently been discovered to function as a neuronal messenger. The presence of NOS was detected in the nervous system of adult Hymenolepis diminuta with NADPH-diaphorase (NADPH-d) histochemistry. The NADPH-d histochemical reaction is regarded as a selective marker for NOS in neuronal tissue. NADPH-d staining was observed in nerve fibres in the main and minor nerve cords and the transverse ring commissures, and in cell bodies in the brain commissure, along the main nerve cords, in the suckers and the rostellar sac. NADPH-d staining was also observed in the wall of the internal seminal vesicle and the genital atrium. The pattern of NADPH-d staining was compared with that of the 5-HT immunoreactive nervous elements. The NADPH-d staining reaction and the 5-HT immunoreactivity occur in separate sets of neurons. This is the first time the NADPH-d reaction has been demonstrated in the nervous system of a flatworm, indicating that NOS is present and that NO can be produced at this level of evolution.

Free gracilis muscle transfer for smile reanimation after treatment for advanced parotid malignancy.

PubMed

Faris, Callum; Heiser, Alyssa; Hadlock, Tessa; Jowett, Nate

2018-03-01

The purpose of this study was to characterize the outcomes of free gracilis muscle transfer for delayed smile reanimation after radical parotidectomy. A retrospective chart review of patients who underwent free gracilis muscle transfer for smile reanimation after radical parotidectomy between 2003 and 2016 was performed. Patient-reported quality of life (Facial Clinimetric Evaluation Scale [FaCE]), physician-reported facial function ("eFACE" facial grading scale), and oral commissure excursion were compared preoperatively and postoperatively. Twelve patients were identified with prior surgery and adjuvant therapy (radiotherapy in 6 cases and chemoradiotherapy in 6 cases). Significant postoperative improvements were demonstrated for ipsilateral commissure excursion with smile (preoperatively: -2.2 mm [SD 2.3 mm] vs postoperatively: 7.9 mm [SD 2.5 mm]; P = .002), with meaningful smile achieved in 11 of 12 cases (91.7%). The average duration of facial paralysis before intervention was 72 months (range 12-204 months). Free gracilis muscle transfer is an option for dynamic smile reanimation in select patients who have undergone treatment for advanced parotid malignancy. © 2017 Wiley Periodicals, Inc.

Iatrogenic left ventricular-right atrial communication after tricuspid annuloplasty; a case report.

PubMed

Tayama, Eiki; Tomita, Yukihiro; Imasaka, Ken-ichi; Kono, Takanori

2014-06-18

A 75-year-old man (Asian, Japanese) was readmitted for examination of a heart murmur and haemolytic anemia 3 months after mitral valve and tricuspid annuloplasties and coronary artery bypass. A new systolic murmur was heard, and echocardiography showed a high-velocity jet originating from the left ventricular outflow tract and extending to the right atrium, a small defect between the left ventricle and the right atrium. No periprosthetic leaks were found in the mitral position. We judged that surgical repair of the defect was essential to treat mechanical haemolysis. At operation, we found a communication (3 mm in diameter) just beneath the detached prosthetic ring at the anteroseptal commissure of the tricuspid valve. After partially removing the tricuspid ring from the anteroseptal commissure area, the defect was closed using a single mattress suture with pledget. In this case, the tricuspid annuloplasty stitch in the atrioventricular region was probably placed on the membranous septum rather than on the tricuspid annulus. A tear then occurred in the atrioventricular membranous septum, leading to left ventricular-right atrial communication.

3D Assessment of Features Associated With Transvalvular Aortic Regurgitation After TAVR: A Real-Time 3D TEE Study.

PubMed

Shibayama, Kentaro; Mihara, Hirotsugu; Jilaihawi, Hasan; Berdejo, Javier; Harada, Kenji; Itabashi, Yuji; Siegel, Robert; Makkar, Raj R; Shiota, Takahiro

2016-02-01

This study of 3-dimensional (3D) transesophageal echocardiography (TEE) aimed to demonstrate features associated with transvalvular aortic regurgitation (AR) after transcatheter aortic valve replacement (TAVR) and to confirm the fact that a gap between the native aortic annulus and prosthesis is associated with paravalvular AR. The mechanism of AR after TAVR, particularly that of transvalvular AR, has not been evaluated adequately. All patients with severe aortic stenosis who underwent TAVR with the Sapien device (Edwards Lifesciences, Irvine, California) had 3D TEE of the pre-procedural native aortic annulus and the post-procedural prosthetic valve. In the 201 patients studied, the total AR was mild in 67 patients (33%), moderate in 21 patients (10%), and severe in no patients. There were 20 patients with transvalvular AR and 82 patients with paravalvular AR. Fourteen patients had both transvalvular and paravalvular AR. Patients with transvalvular AR had larger prosthetic expansion (p <0.05), a more elliptical prosthetic shape at the prosthetic commissure level (p <0.01) and more anti-anatomical position (p <0.001), which was defined as malposition of the prosthetic commissures in relation to the native commissures, than the patients without transvalvular AR. Age (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 1.01 to 1.09; p < 0.05) and effective area oversizing (OR: 0.97; 95% CI: 0.93 to 0.99, p <0.05) were associated with mild or greater paravalvular AR. 3D TEE successfully demonstrated the features associated with transvalvular AR, such as large prosthetic expansion, elliptical prosthetic shape, and anti-anatomical position of prosthesis. Additionally, effective area oversizing was associated with paravalvular AR. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Durability of Aortic Valve Cusp Repair With and Without Annular Support.

PubMed

Zeeshan, Ahmad; Idrees, Jay J; Johnston, Douglas R; Rajeswaran, Jeevanantham; Roselli, Eric E; Soltesz, Edward G; Gillinov, A Marc; Griffin, Brian; Grimm, Richard; Hammer, Donald F; Pettersson, Gösta B; Blackstone, Eugene H; Sabik, Joseph F; Svensson, Lars G

2018-03-01

To determine the value of aortic valve repair rather than replacement for valve dysfunction, we assessed late outcomes of various repair techniques in the contemporary era. From January 2001 to January 2011, aortic valve repair was planned in 1,124 patients. Techniques involved commissural figure-of-8 suspension sutures (n = 63 [6.2%]), cusp repair with commissuroplasty (n = 481 [48%]), debridement (n = 174 [17%]), free-margin plication (n = 271 [27%]) or resection (n = 75) or both, or annulus repair with resuspension (n = 230 [23%]), root reimplantation (n = 252 [25%]), or remodeling (n = 35 [3.5%]). Planned repair was aborted for replacement in 115 patients (10%); risk factors included greater severity of aortic regurgitation (AR; p = 0.0002) and valve calcification (p < 0.0001). In-hospital outcomes for the remaining 1,009 patients included death (12 [1.2%]), stroke (13 [1.3%]), and reoperation for valve dysfunction (14 [1.4%]). Freedom from aortic valve reoperation at 1, 5, and 10 years was 97%, 93%, and 90%, respectively. Figure-of-8 suspension sutures, valve resuspension, and root repair and replacement were least likely to require reoperation; cusp repair with commissural sutures, plication, and commissuroplasty was most likely (p < 0.05). Survival at 1, 5, and 10 years was 96%, 92%, and 83%. Immediate postoperative AR grade was none-mild (94%), moderate (5%), and severe (1%). At 10 years after repair, AR grade was none (20%), mild (33%), moderate (26%), and severe (21%). Patients undergoing root procedures were less likely to have higher-grade postoperative AR (p < 0.0001). Valve repair is effective and durable for treating aortic valve dysfunction. Greater severity of AR preoperatively is associated with higher likelihood of repair failure. Commissural figure-of-8 suspension sutures and repair with annular support have the best long-term durability. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Stent and leaflet stresses in a 26-mm first-generation balloon-expandable transcatheter aortic valve.

PubMed

Xuan, Yue; Krishnan, Kapil; Ye, Jian; Dvir, Danny; Guccione, Julius M; Ge, Liang; Tseng, Elaine E

2017-05-01

Transcatheter aortic valve replacement is established therapy for high-risk and inoperable patients with severe aortic stenosis, but questions remain regarding long-term durability. Valve design influences durability. Increased leaflet stresses in surgical bioprostheses have been correlated with degeneration; however, transcatheter valve leaflet stresses are unknown. From 2007 to 2014, a majority of US patients received first-generation balloon-expandable transcatheter valves. Our goal was to determine stent and leaflet stresses in this valve design using finite element analyses. A 26-mm Sapien Transcatheter Heart Valve (Edwards Lifesciences, Inc, Irvine, Calif) underwent high-resolution microcomputed tomography scanning to develop precise 3-dimensional geometry of the leaflets, the stent, and the polyethylene terephthalate elements. The stent was modeled using 3-dimensional elements and the leaflets were modeled using shell elements. Stent material properties were based on stainless steel, whereas those for leaflets were obtained from surgical bioprostheses. Noncylindrical Sapien valve geometry was also simulated. Pressure loading to 80 mm Hg and 120 mm Hg was performed using ABAQUS finite element software (Dassault Systèmes, Waltham, Mass). At 80 mm Hg, maximum principal stresses on Sapien leaflets were 1.31 megaspascals (MPa). Peak leaflet stress was observed at commissural tips where leaflets connected to the stent. Maximum principal stresses for the stent were 188.91 MPa and located at stent tips where leaflet commissures were attached. Noncylindrical geometry increased peak principal leaflet stresses by 16%. Using exact geometry from high-resolution scans, the 26-mm Sapien Transcatheter Heart Valve showed that peak stresses for both stent and leaflets were present at commissural tips where leaflets were attached. These regions would be prone to leaflet degeneration. Understanding stresses in first-generation transcatheter valves allows comparison to future designs for relative durability. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Effect of Weakening of Ipsilateral Depressor Anguli Oris on Smile Symmetry in Postparalysis Facial Palsy.

PubMed

Jowett, Nate; Malka, Ronit; Hadlock, Tessa A

2017-01-01

Aberrant depressor anguli oris (DAO) activity may arise after recovery from acute facial paralysis and restrict movement of the oral commissure. To quantify the degree to which DAO inhibition affects smile dynamics and perceived emotional state. In this prospective, pretest-posttest study performed at an academic tertiary referral hospital, patients with unilateral postparalysis facial palsy were studied from January 16 through April 30, 2016. Local anesthetic injection into the ipsilateral DAO. Healthy- and paretic-side commissure displacements from the midline lower vermillion border referenced to the horizontal plane were calculated from random-ordered photographs of full-effort smile before and after injection, and random-ordered hemifacial photographs of the paretic side were assessed as expressing positive, negative, or indiscernible emotion. Twenty patients were identified as having unilateral postparalysis facial palsy with marked synkinesis of the ipsilateral DAO. Patient mean age was 46 years (range, 24-67 years), with a male to female ratio of 1:3. Mean paretic-side commissure displacement increased from 27.45 mm at 21.65° above the horizontal plane to 29.35 mm at 23.58° after DAO weakening (mean difference, 1.90 mm; 95% CI, 1.26-2.54 mm; and 1.93°; 95% CI, 0.34°-3.51°; P < .001 and P = .20, respectively). Symmetry of excursion between sides improved by 2.00 mm (95% CI, 1.16-2.83 mm; P < .001) and 2.71° (95% CI, 1.38°-4.03°; P < .001). At baseline, observers assessed 7 of 20 paretic hemifaces (35%) as expressing positive emotion; this proportion increased to 13 of 20 (65%) after DAO weakening (P = .03). Ipsilateral DAO weakening results in significant improvements in smile dynamics and perceived expression of positive emotion on the paretic hemiface in postparalysis facial palsy. A trial of DAO weakening should be offered to patients with this disfiguring complication of Bell palsy and similar facial nerve insults. 3.

Vulvar epithelioid hemangiosarcoma with solar elastosis in a mare.

PubMed

Gumber, Sanjeev; Baia, Petrisor; Wakamatsu, Nobuko

2011-09-01

A 15-year-old female gray Appaloosa horse was presented with history of a mass over the right dorsal commissure of vulva for the past 7 months. Based on histopathological examination, and positive staining with factor VIII-related antigen, vimentin, and Verhoeff-van Gieson stain, the vulvar mass was diagnosed as hemangiosarcoma with marked solar elastosis.

Percutaneous focused force aortic valvuloplasty using the buddy-catheter technique.

PubMed

Tada, Norio; Ootomo, Tatsushi; Meguro, Taiichiro

2012-06-01

Percutaneous transcatheter aortic valvuloplasty is seriously limited by high restenosis rates. We report a case where the use of a buddy-catheter technique during balloon inflation allowed increased focused force onto calcified stiff commissures with an increase in resultant valve area. This technique may result in further valve area enlargement and decrease the restenosis rate.

Comminuted Laryngeal Fracture Following Blunt Trauma: A Need for Strict Legislation on Roads!

PubMed

Jain, Shraddha; Singh, Pragya; Gupta, Minal; Kamble, Bhavna; Phatak, Suresh S

2017-01-01

Laryngeal fracture is a rare condition with potential life-long implications related to airway patency, voice quality, and swallowing. Rarity of the condition leads to lack of consensus on the most suitable way to manage this injury. The mode of injury can be prevented by strict legislation on the roads. We report a case of a 28-year-old Indian male who sustained a comminuted displaced fracture of the thyroid cartilage with disruption of anterior commissure due to blunt trauma caused by the metallic side rod of a ladder projecting from the rear of a vehicle in front of the bike on which he was riding. He presented with breathing difficulty, change in voice, surgical emphysema, and pneumomediastinum, but without any skin changes over the neck. His airway could be restored due to early tracheostomy and open reduction with internal fixation with sutures along with laryngeal stenting. He has no significant swallowing or breathing problem and reasonably good voice 6 months after surgery. This case highlights the need for strict legislation on roads in India and the importance of high level of suspicion for laryngeal fracture in acute trauma patient. Early identification and timely internal fixation not only restore the airway but also improve long-term voice and airway outcomes.

Anatomy and physiology of neurons with processes in the accessory medulla of the cockroach Leucophaea maderae.

PubMed

Loesel, R; Homberg, U

2001-10-15

The accessory medulla (AMe), a small neuropil in the insect optic lobe, has been proposed to serve a circadian pacemaker function analogous to the role of the suprachiasmatic nucleus in mammals. Building upon considerable knowledge of the circadian system of the cockroach Leucophaea maderae, we investigated the properties of AMe neurons in this insect with intracellular recordings combined with dye injections. Responses of neurons with processes in the AMe to visual stimuli, including stationary white light, moving objects, and polarized light were compared with the responses of adjacent medulla tangential neurons. Neurons with processes in the AMe and additional ramifications in the medulla strongly responded to stationary light stimuli and might, therefore, be part of photic entrainment pathways to the clock. Accessory medulla neurons lacking significant processes in the medulla but with projections to the midbrain or to the contralateral optic lobe, in contrast, responded weakly or not at all to light and, thus, seem to be part of the clock's output pathway. Two types of commissural neurons with tangential arborizations in both medullae were sensitive to polarized light, suggesting a role of these neurons in celestial navigation. Sidebranches in the AMae of one of the two cell types are discussed with respect to a possible involvement of the AMe in polarization vision. Finally, neurons responding to movement stimuli did not arborize in the AMe. The results show that the AMe receives photic input and support a role of this neuropil in circadian timekeeping functions. Copyright 2001 Wiley-Liss, Inc.

Elevation of the Corner of the Mouth Using Botulinum Toxin Type A

PubMed Central

Goldman, Alberto; Wollina, Uwe

2010-01-01

Indications for botulinum toxin type A have been constantly evolving, and it can currently be used in virtually any area of the face and neck. The authors present their experience with this neurotoxin in treating the platysmal bands and depressor anguli oris muscle with the purpose of cosmetically improving the anterior neck and lifting the oral commissure. PMID:21430826

Development of a novel constellation based landmark detection algorithm

NASA Astrophysics Data System (ADS)

Ghayoor, Ali; Vaidya, Jatin G.; Johnson, Hans J.

2013-03-01

Anatomical landmarks such as the anterior commissure (AC) and posterior commissure (PC) are commonly used by researchers for co-registration of images. In this paper, we present a novel, automated approach for landmark detection that combines morphometric constraining and statistical shape models to provide accurate estimation of landmark points. This method is made robust to large rotations in initial head orientation by extracting extra information of the eye centers using a radial Hough transform and exploiting the centroid of head mass (CM) using a novel estimation approach. To evaluate the effectiveness of this method, the algorithm is trained on a set of 20 images with manually selected landmarks, and a test dataset is used to compare the automatically detected against the manually detected landmark locations of the AC, PC, midbrain-pons junction (MPJ), and fourth ventricle notch (VN4). The results show that the proposed method is accurate as the average error between the automatically and manually labeled landmark points is less than 1 mm. Also, the algorithm is highly robust as it was successfully run on a large dataset that included different kinds of images with various orientation, spacing, and origin.

Arterial switch: translocation of the intramural coronary artery.

PubMed

Asou, T; Karl, T R; Pawade, A; Mee, R B

1994-02-01

Translocation of an intramural coronary artery is one of the most challenging problems in anatomic correction of transposition of the great arteries. Of 259 patients undergoing arterial switch procedure for transposition of the great arteries in our hospital, 12 (4.6%) were found to have intramural coronary arteries. The diagnosis was made intraoperatively in all patients. There were five different types of intramural coronary anatomy noted, with ostial stenosis present in half. The operative technique consisted of detachment of the posterior commissure of the aortic valve and unroofing of the intramural segment of the coronary artery by excision of a triangular portion of internal aortic wall. The coronary arteries were excised as a single disc, which was divided into two cuffs. The arterial switch was then performed in the usual fashion. The posterior commissure of the aortic valve was resuspended to the pericardial patch used to reconstruct the neopulmonary artery sinus. There were no operative or late deaths over a follow-up of 328 patient-months. Postoperatively, no patient showed ischemic changes on electrocardiogram or abnormal wall motion on echocardiogram. We believe that intramural coronary arteries can be managed satisfactorily with this technique, and that arterial switch will be possible in all cases.

Complete prefrontal lobe isolation surgery for recurrent epilepsy: A case report

PubMed Central

Yin, Shaoya; Jin, Weipeng; Li, Qingyun; Feng, Mei; Feng, Keke; Shao, Hui; Zhang, Xueqing; Wang, Shimin

2016-01-01

Epileptogenic focus resection is less effective for the treatment of frontal lobe epilepsy compared with temporal lobe epilepsy. However, there is currently a lack of effective therapeutic options for patients with frontal lobe epilepsy who are unsuitable for epileptogenic focus resection (such patients with epileptogenic foci in one frontal lobe in which the precise epileptic foci cannot be determined), or who experience recurrent epilepsy following epileptogenic focus resection. The present study reports a patient with frontal lobe epilepsy who underwent successful frontal lobe isolation surgery following a previous unsuccessful epileptogenic focus resection surgery. To ensure complete isolation of the prefrontal lobe, the surgery included division of the anterior commissure and the anterior part of the corpus callosum. The patient was followed-up for 16 months. Although the follow-up electroencephalogram presented a number of sharp waves on the affected side, the patient did not experience any seizures. The results suggest that prefrontal lobe isolation is an effective method of treating frontal lobe epilepsy, as division of the anterior commissure and the anterior part of the corpus callosum ensures disconnection of the prefrontal lobe from other regions of the brain. PMID:27882111

The supraciliary space as a suitable pathway for glaucoma surgery: Ho-hum or home run?

PubMed

Figus, Michele; Posarelli, Chiara; Passani, Andrea; Albert, Timothy G; Oddone, Francesco; Sframeli, Angela Tindara; Nardi, Marco

The supraciliary space is a physiological route for aqueous humor outflow located anteriorly between the outer surface of the ciliary body and the internal surface of the sclera. Posteriorly, the suprachoroidal space is located between the choroid and the internal surface of the sclera. These spaces have been targeted as suitable and helpful pathways for glaucoma treatment, alternatives to the traditional subconjunctival space. The subconjunctival surgical pathway is affected by several limitations such as poor cosmesis, a lifetime risk for endophthalmitis, and an unpredictable wound healing response. Because of these limitations, the supraciliary space has gained growing interest as a possible target for new glaucoma drainage devices such as: Gold Micro Shunt (SOLX Inc.; Waltham, MA, USA), iStent Supra (Glaukos Corporation, Laguna Hills, CA, USA), CyPass Micro-Stent (Transcend Medical Inc., Menlo Park, CA, USA), Aquashunt (OPKO health Inc., Miami, FL, USA), STARflo (iSTAR Medical, Isnes, Belgium), and Esnoper-Clip implant (AJL Ophthalmics, Álava, Spain). We review the current literature concerning the supraciliary space to evaluate its safety and efficacy as a suitable pathway for glaucoma surgical treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

3D echocardiographic location of implantable device leads and mechanism of associated tricuspid regurgitation.

PubMed

Mediratta, Anuj; Addetia, Karima; Yamat, Megan; Moss, Joshua D; Nayak, Hemal M; Burke, Martin C; Weinert, Lynn; Maffessanti, Francesco; Jeevanandam, Valluvan; Mor-Avi, Victor; Lang, Roberto M

2014-04-01

This study sought to: 1) determine the feasibility of using 3-dimensional transthoracic echocardiography (3D TTE) in patients with implantable cardiac resynchronization devices, pacemakers, and defibrillators to visualize the device leads in the right heart and their position relative to the tricuspid valve leaflets; 2) determine the prevalence of different lead positions; and 3) study the relationship between lead location and tricuspid regurgitation (TR) severity. Pacemaker, defibrillator, and cardiac resynchronization device implantation is currently guided by fluoroscopy, not allowing targeted lead positioning relative to the tricuspid valve leaflets. These leads have been reported to cause TR of variable degrees, but echocardiography is not routinely used to elucidate the mechanisms of lead interference with tricuspid valve leaflets in individual patients. 3D TTE full-volume images of the right ventricle and/or zoomed images of the tricuspid valve were obtained in 121 patients with implanted devices. Images were viewed offline to determine the position of the device-lead relative to the tricuspid valve leaflets. Severity of TR was estimated on the basis of vena contracta measurements. 3D TTE clearly depicted lead position in 90% of patients. The right ventricular lead was impinging on either the posterior (20%) or septal (23%) leaflet or was not interfering with leaflet motion (53%) when positioned near the posteroseptal commissure or in the central portion of the tricuspid valve orifice. In the remaining patients, leads were impinging on the anterior leaflet (4%) or positioned in either the anteroposterior or anteroseptal commissure (3%). Leads interfering with normal leaflet mobility were associated with more TR than nonimpinging leads (vena contracta: median 0.62 cm [1st and 3rd quartiles: 0.51, 0.84 cm] vs. 0.27 cm [1st and 3rd quartiles: 0.00, 0.48 cm]; p < 0.001). 3D TTE showed a clear association between device lead position and TR. To minimize TR induced by device-leads, 3D TTE guidance should be considered for placement in a commissural position. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Transient Hypothyroidism During Lactation Arrests Myelination in the Anterior Commissure of Rats. A Magnetic Resonance Image and Electron Microscope Study.

PubMed

Lucia, Federico S; Pacheco-Torres, Jesús; González-Granero, Susana; Canals, Santiago; Obregón, María-Jesús; García-Verdugo, José M; Berbel, Pere

2018-01-01

Thyroid hormone deficiency at early postnatal ages affects the cytoarchitecture and function of neocortical and telencephalic limbic areas, leading to impaired associative memory and in a wide spectrum of neurological and mental diseases. Neocortical areas project interhemispheric axons mostly through the corpus callosum and to a lesser extent through the anterior commissure (AC), while limbic areas mostly project through the AC and hippocampal commissures. Functional magnetic resonance data from children with late diagnosed congenital hypothyroidism and abnormal verbal memory processing, suggest altered ipsilateral and contralateral telencephalic connections. Gestational hypothyroidism affects AC development but the possible effect of transient and chronic postnatal hypothyroidism, as occurs in late diagnosed neonates with congenital hypothyroidism and in children growing up in iodine deficient areas, still remains unknown. We studied AC development using in vivo magnetic resonance imaging and electron microscopy in hypothyroid and control male rats. Four groups of methimazole (MMI) treated rats were studied. One group was MMI-treated from postnatal day (P) 0 to P21; some of these rats were also treated with L-thyroxine (T4) from P15 to P21, as a model for early transient hypothyroidism. Other rats were MMI-treated from P0 to P150 and from embryonic day (E) 10 to P170, as a chronic hypothyroidism group. The results were compared with age paired control rats. The normalized T2 signal using magnetic resonance image was higher in MMI-treated rats and correlated with the number and percentage of myelinated axons. Using electron microscopy, we observed decreased myelinated axon number and density in transient and chronic hypothyroid rats at P150, unmyelinated axon number increased slightly in chronic hypothyroid rats. In MMI-treated rats, the myelinated axon g-ratio and conduction velocity was similar to control rats, but with a decrease in conduction delays. These data show that early postnatal transient and chronic hypothyroidism alters AC maturation that may affect the transfer of information through the AC. The alterations cannot be recovered after delayed T4-treatment. Our data support the neurocognitive delay found in late T4-treated children with congenital hypothyroidism.

Three-dimensional stereophotogrammetric analysis of 50 smiles: A study of dento-facial proportions.

PubMed

Ceinos, R; Lupi, L; Tellier, A; Bertrand, M F

2017-11-12

The purpose of this study was to analyze 50 smiles using 3D stereophotogrammetry (3D-spg)-based facial reconstruction, to calculate ratios involving measurements of the distances between dental and facial landmarks and to compare these ratios with the golden ratio φ (1.618). Fifty subjects with no obvious malocclusion participated in this study. For each subject, 4 photographs were acquired using the LifeViz Mini™, an absolute calibration 3D-spg system. Facial and dental landmarks (based on Farkas' definitions) were fixed, and 8 distances were measured. Four ratios were then calculated and compared with the value of 1.618. The ratio "incisal edge of the maxillary central incisor-lower border of the chin/subnasal point-incisal edge of the maxillary central incisor" (IE-Me/SN-IE) was 1.693 ± 0.190, the ratio "right endocanthion-left endocanthion/right exocanthion-right endocanthion" was 1.582 ± 0.173, the ratio "incisal edge of the maxillary central incisor-distal edge of the right canine/distal edge of the right canine-right labial commissure" was 1.670 ± 0.355, and the ratio "right labial commissure-left labial commissure/distal edge of the right canine-distal edge of the left canine" was 1.602 ± 0.136. In contrast, the vertical ratio IE-Me/SN-IE significantly differed from the golden ratio (1 sample t test, P = .009). This study revealed that the observed ratios were surprisingly close to the golden ratio. Only the vertical ratio differed from the golden ratio, whereas the horizontal ratios appear to be adequately approximated by φ. If the distances from reference points of the face to teeth within a harmonious smile exhibited recurring esthetic proportions, knowledge of such ratios would provide an additional tool for the elaboration of esthetic treatment plans. In addition, this knowledge could provide guidance when planning tooth positions and dental proportions by encouraging consideration of the global nature of the oro-facial sphere. © 2017 Wiley Periodicals, Inc.

Microstructural Correlates of Emotional Attribution Impairment in Non-Demented Patients with Amyotrophic Lateral Sclerosis.

PubMed

Crespi, Chiara; Cerami, Chiara; Dodich, Alessandra; Canessa, Nicola; Iannaccone, Sandro; Corbo, Massimo; Lunetta, Christian; Falini, Andrea; Cappa, Stefano F

2016-01-01

Impairments in the ability to recognize and attribute emotional states to others have been described in amyotrophic lateral sclerosis patients and linked to the dysfunction of key nodes of the emotional empathy network. Microstructural correlates of such disorders are still unexplored. We investigated the white-matter substrates of emotional attribution deficits in a sample of amyotrophic lateral sclerosis patients without cognitive decline. Thirteen individuals with either probable or definite amyotrophic lateral sclerosis and 14 healthy controls were enrolled in a Diffusion Tensor Imaging study and administered the Story-based Empathy Task, assessing the ability to attribute mental states to others (i.e., Intention and Emotion attribution conditions). As already reported, a significant global reduction of empathic skills, mainly driven by a failure in Emotion Attribution condition, was found in amyotrophic lateral sclerosis patients compared to healthy subjects. The severity of this deficit was significantly correlated with fractional anisotropy along the forceps minor, genu of corpus callosum, right uncinate and inferior fronto-occipital fasciculi. The involvement of frontal commissural fiber tracts and right ventral associative fronto-limbic pathways is the microstructural hallmark of the impairment of high-order processing of socio-emotional stimuli in amyotrophic lateral sclerosis. These results support the notion of the neurofunctional and neuroanatomical continuum between amyotrophic lateral sclerosis and frontotemporal dementia.

White matter and schizophrenia: A meta-analysis of voxel-based morphometry and diffusion tensor imaging studies.

PubMed

Vitolo, Enrico; Tatu, Mona Karina; Pignolo, Claudia; Cauda, Franco; Costa, Tommaso; Ando', Agata; Zennaro, Alessandro

2017-12-30

Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) are the most implemented methodologies to detect alterations of both gray and white matter (WM). However, the role of WM in mental disorders is still not well defined. We aimed at clarifying the role of WM disruption in schizophrenia and at identifying the most frequently involved brain networks. A systematic literature search was conducted to identify VBM and DTI studies focusing on WM alterations in patients with schizophrenia compared to control subjects. We selected studies reporting the coordinates of WM reductions and we performed the anatomical likelihood estimation (ALE). Moreover, we labeled the WM bundles with an anatomical atlas and compared VBM and DTI ALE-scores of each significant WM tract. A total of 59 studies were eligible for the meta-analysis. WM alterations were reported in 31 and 34 foci with VBM and DTI methods, respectively. The most occurred WM bundles in both VBM and DTI studies and largely involved in schizophrenia were long projection fibers, callosal and commissural fibers, part of motor descending fibers, and fronto-temporal-limbic pathways. The meta-analysis showed a widespread WM disruption in schizophrenia involving specific cerebral circuits instead of well-defined regions. Copyright © 2017 Elsevier B.V. All rights reserved.

Microstructural Correlates of Emotional Attribution Impairment in Non-Demented Patients with Amyotrophic Lateral Sclerosis

PubMed Central

Cerami, Chiara; Dodich, Alessandra; Canessa, Nicola; Iannaccone, Sandro; Corbo, Massimo; Lunetta, Christian; Falini, Andrea; Cappa, Stefano F.

2016-01-01

Impairments in the ability to recognize and attribute emotional states to others have been described in amyotrophic lateral sclerosis patients and linked to the dysfunction of key nodes of the emotional empathy network. Microstructural correlates of such disorders are still unexplored. We investigated the white-matter substrates of emotional attribution deficits in a sample of amyotrophic lateral sclerosis patients without cognitive decline. Thirteen individuals with either probable or definite amyotrophic lateral sclerosis and 14 healthy controls were enrolled in a Diffusion Tensor Imaging study and administered the Story-based Empathy Task, assessing the ability to attribute mental states to others (i.e., Intention and Emotion attribution conditions). As already reported, a significant global reduction of empathic skills, mainly driven by a failure in Emotion Attribution condition, was found in amyotrophic lateral sclerosis patients compared to healthy subjects. The severity of this deficit was significantly correlated with fractional anisotropy along the forceps minor, genu of corpus callosum, right uncinate and inferior fronto-occipital fasciculi. The involvement of frontal commissural fiber tracts and right ventral associative fronto-limbic pathways is the microstructural hallmark of the impairment of high-order processing of socio-emotional stimuli in amyotrophic lateral sclerosis. These results support the notion of the neurofunctional and neuroanatomical continuum between amyotrophic lateral sclerosis and frontotemporal dementia. PMID:27513746

Diversity of layer 5 projection neurons in the mouse motor cortex

PubMed Central

Oswald, Manfred J.; Tantirigama, Malinda L. S.; Sonntag, Ivo; Hughes, Stephanie M.; Empson, Ruth M.

2013-01-01

In the primary motor cortex (M1), layer 5 projection neurons signal directly to distant motor structures to drive movement. Despite their pivotal position and acknowledged diversity these neurons are traditionally separated into broad commissural and corticofugal types, and until now no attempt has been made at resolving the basis for their diversity. We therefore probed the electrophysiological and morphological properties of retrogradely labeled M1 corticospinal (CSp), corticothalamic (CTh), and commissural projecting corticostriatal (CStr) and corticocortical (CC) neurons. An unsupervised cluster analysis established at least four phenotypes with additional differences between lumbar and cervical projecting CSp neurons. Distinguishing parameters included the action potential (AP) waveform, firing behavior, the hyperpolarisation-activated sag potential, sublayer position, and soma and dendrite size. CTh neurons differed from CSp neurons in showing spike frequency acceleration and a greater sag potential. CStr neurons had the lowest AP amplitude and maximum rise rate of all neurons. Temperature influenced spike train behavior in corticofugal neurons. At 26°C CTh neurons fired bursts of APs more often than CSp neurons, but at 36°C both groups fired regular APs. Our findings provide reliable phenotypic fingerprints to identify distinct M1 projection neuron classes as a tool to understand their unique contributions to motor function. PMID:24137110

Allosteric potentiation of quisqualate receptors by a nootropic drug aniracetam.

PubMed

Ito, I; Tanabe, S; Kohda, A; Sugiyama, H

1990-05-01

1. Allosteric potentiation of the ionotropic quisqualate (iQA) receptor by a nootropic drug aniracetam (1-p-anisoyl-2-pyrrolidinone) was investigated using Xenopus oocytes injected with rat brain mRNA and rat hippocampal slices. 2. Aniracetam potentiates the iQA responses induced in Xenopus oocytes by rat brain mRNA in a reversible manner. This effect was observed above the concentrations of 0.1 mM. Kainate. N-methyl-D-aspartate and gamma-aminobutyric acid responses induced in the same oocytes were not affected. 3. The specific potentiation of iQA responses was accompanied by an increase in the conductance change of iQA and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) responses, but the affinity of receptors for agonist and the ion-selectivity of the channels (reversal potentials) were not changed. 4. Aniracetam reversibly potentiated the iQA responses recorded intracellularly from the pyramidal cells in the CA1 region of rat hippocampal slices. The excitatory postsynaptic potentials (EPSPs) in Schaffer collateral-commissural-CA1 synapses were also potentiated by aniracetam. 5. Population EPSPs recorded in the mossy fibre-CA3 synapses as well as Schaffer-commissural synapses were also potentiated by aniracetam. The amplitudes of the potentiation were not changed by the formation of long-term potentiation.

Allosteric potentiation of quisqualate receptors by a nootropic drug aniracetam.

PubMed Central

Ito, I; Tanabe, S; Kohda, A; Sugiyama, H

1990-01-01

1. Allosteric potentiation of the ionotropic quisqualate (iQA) receptor by a nootropic drug aniracetam (1-p-anisoyl-2-pyrrolidinone) was investigated using Xenopus oocytes injected with rat brain mRNA and rat hippocampal slices. 2. Aniracetam potentiates the iQA responses induced in Xenopus oocytes by rat brain mRNA in a reversible manner. This effect was observed above the concentrations of 0.1 mM. Kainate. N-methyl-D-aspartate and gamma-aminobutyric acid responses induced in the same oocytes were not affected. 3. The specific potentiation of iQA responses was accompanied by an increase in the conductance change of iQA and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) responses, but the affinity of receptors for agonist and the ion-selectivity of the channels (reversal potentials) were not changed. 4. Aniracetam reversibly potentiated the iQA responses recorded intracellularly from the pyramidal cells in the CA1 region of rat hippocampal slices. The excitatory postsynaptic potentials (EPSPs) in Schaffer collateral-commissural-CA1 synapses were also potentiated by aniracetam. 5. Population EPSPs recorded in the mossy fibre-CA3 synapses as well as Schaffer-commissural synapses were also potentiated by aniracetam. The amplitudes of the potentiation were not changed by the formation of long-term potentiation. PMID:1975272

Distribution of glycogen phosphorylase and cytochrome oxidase in the central nervous system of the turtle Trachemys dorbigni.

PubMed

Partata, W A; Krepsky, A M; Xavier, L L; Marques, M; Achaval, M

1999-10-01

Glycogen phosphorylase (GP) and cytochrome oxidase (CO) activities were mapped histochemically in the brain of the turtle Trachemys dorbigni. In the telencephalon, both activities occurred in the olfactory bulb, in all cortical areas, in the dorsal ventricular ridge, striatum, primordium hippocampi and olfactory tubercle. In the diencephalon, they were identified in some areas of the hypothalamus, and in rotundus and geniculate nuclei. Both reactions were detected in the oculomotor, trochlear, mesencephalic trigeminal nuclei, the nucleus of the posterior commissure, torus semicircularis, substantia nigra and ruber and isthmic nuclei of the mesencephalon. In all layers of the optic tectum GP activity was found, but CO only labelled the stratum griseum centrale. In the medulla oblonga both enzymes appear in the reticular, raphe and vestibular nuclei, locus coeruleus and nuclei of cranial nerves. In the cerebellum, the granular and molecular layers, and the deep cerebellar nuclei were positive for both enzymes. The Purkinje cells were only reactive for CO. In the spinal cord, motor and commissural neurones exhibited a positive reaction for the two enzymes. However, CO also occurred in the marginal nucleus and in the lateral funiculus. These results may be useful as a basis for subsequent studies on turtle brain metabolism.

Habenular commissure formation in zebrafish is regulated by the pineal gland-specific gene unc119c.

PubMed

Toyama, Reiko; Kim, Mi Ha; Rebbert, Martha L; Gonzales, John; Burgess, Harold; Dawid, Igor B

2013-09-01

The zebrafish pineal gland (epiphysis) is a site of melatonin production, contains photoreceptor cells, and functions as a circadian clock pacemaker. Since it is located on the surface of the forebrain, it is accessible for manipulation and, therefore, is a useful model system to analyze pineal gland function and development. We previously analyzed the pineal transcriptome during development and showed that many genes exhibit a highly dynamic expression pattern in the pineal gland. Among genes preferentially expressed in the zebrafish pineal gland, we identified a tissue-specific form of the unc119 gene family, unc119c, which is highly preferentially expressed in the pineal gland during day and night at all stages examined from embryo to adult. When expression of unc119c was inhibited, the formation of the habenular commissure (HC) was specifically compromised. The Unc119c interacting factors Arl3l1 and Arl3l2 as well as Wnt4a also proved indispensible for HC formation. We suggest that Unc119c, together with Arl3l1/2, plays an important role in modulating Wnt4a production and secretion during HC formation in the forebrain of the zebrafish embryo. Copyright © 2013 Wiley Periodicals, Inc.

Habenular commissure formation in zebrafish is regulated by the pineal gland specific gene unc119c

PubMed Central

Toyama, Reiko; Kim, Mi Ha; Rebbert, Martha L.; Gonzales, John; Burgess, Harold; Dawid, Igor B.

2013-01-01

Background The zebrafish pineal gland (epiphysis) is a site of melatonin production, contains photoreceptor cells, and functions as a circadian clock pacemaker. Since it is located on the surface of the forebrain, it is accessible for manipulation and therefore is a useful model system to analyze pineal gland function and development. We previously analyzed the pineal transcriptome during development and showed that many genes exhibit a highly dynamic expression pattern in the pineal gland. Results Among genes preferentially expressed in the zebrafish pineal gland, we identified a tissue-specific form of the unc119 gene family, unc119c, which is highly preferentially expressed in the pineal gland during day and night at all stages examined from embryo to adult. When expression of unc119c was inhibited, the formation of the habenular commissure (HC) was specifically compromised. The Unc119c interacting factors Arl3l1 and Arl3l2 as well as Wnt4a also proved indispensible for HC formation. Conclusions We suggest that Unc119c, together with Arl3l1/2, plays an important role in modulating Wnt4a production and secretion during HC formation in the forebrain of the zebrafish embryo. PMID:23749482

Subvalvular Pannus Overgrowth after Mosaic Bioprosthesis Implantation in the Aortic Position

PubMed Central

Isomura, Tadashi; Yoshida, Minoru; Katsumata, Chieko; Ito, Fusahiko; Watanabe, Masazumi

2015-01-01

Purpose: Although pannus overgrowth by itself was not the pathology of structural valve deterioration (SVD), it might be related to reoperation for SVD of the bioprostheses. Methods: We retrospectively reviewed patients undergoing reoperation for SVD after implantation of the third-generation Mosaic aortic bioprosthesis and macroscopic appearance of the explanted valves was examined to detect the presence of pannus. Results: There were 10 patients and the age for the initial aortic valve replacement was 72 ± 10 years old. The duration of durability was 9.9 ± 2.0 years. Deteriorated valve presented stenosis (valvular area of 0.96 ± 0.20 cm2; pressure gradient of 60 ± 23 mmHg). Coexisting regurgitant flow was detected in two cases. Macroscopically, subvalvular pannus overgrowth was detected in 8 cases (80%). The proportion of overgrowth from the annulus was almost even and pannus overgrowth created subvalvular membrane, which restricted the area especially for each commissure. In contrast, opening and mobility of each leaflet was not severely limited and pannus overgrowth would restrict the area, especially for each commissure. In other two cases with regurgitation, tear of the leaflet on the stent strut was detected and mild calcification of each leaflet restricted opening. Conclusion: In patients with the Mosaic aortic bioprosthesis, pannus overgrowth was the major cause for reoperation. PMID:26633541

Subvalvular Pannus Overgrowth after Mosaic Bioprosthesis Implantation in the Aortic Position.

PubMed

Hirota, Masanori; Isomura, Tadashi; Yoshida, Minoru; Katsumata, Chieko; Ito, Fusahiko; Watanabe, Masazumi

2016-01-01

Although pannus overgrowth by itself was not the pathology of structural valve deterioration (SVD), it might be related to reoperation for SVD of the bioprostheses. We retrospectively reviewed patients undergoing reoperation for SVD after implantation of the third-generation Mosaic aortic bioprosthesis and macroscopic appearance of the explanted valves was examined to detect the presence of pannus. There were 10 patients and the age for the initial aortic valve replacement was 72 ± 10 years old. The duration of durability was 9.9 ± 2.0 years. Deteriorated valve presented stenosis (valvular area of 0.96 ± 0.20 cm(2); pressure gradient of 60 ± 23 mmHg). Coexisting regurgitant flow was detected in two cases. Macroscopically, subvalvular pannus overgrowth was detected in 8 cases (80%). The proportion of overgrowth from the annulus was almost even and pannus overgrowth created subvalvular membrane, which restricted the area especially for each commissure. In contrast, opening and mobility of each leaflet was not severely limited and pannus overgrowth would restrict the area, especially for each commissure. In other two cases with regurgitation, tear of the leaflet on the stent strut was detected and mild calcification of each leaflet restricted opening. In patients with the Mosaic aortic bioprosthesis, pannus overgrowth was the major cause for reoperation.

When Not to Go SOLO? Contraindications Based on Implant Experience.

PubMed

Wollersheim, Laurens W; Li, Wilson W; Kaya, Abdullah; van Boven, Wim J; van der Meulen, Jan; de Mol, Bas A

2016-11-01

Because of the design and specific implantation technique of the stentless Freedom SOLO bioprosthesis, patient selection is crucial. The aim of the study was to discuss the contraindications to this prosthesis based on the authors' implant experience. Between April 2005 and February 2015, one surgeon at the authors' center performed 292 aortic valve replacements using a bioprosthesis, with the initial intention of implanting a SOLO valve in every patient. A search was conducted for all of these patients and data collected on whether a SOLO valve was used, or not. A SOLO valve was implanted in 238 patients (82%), and a stented bioprosthesis in 54 (18%). The predominant reasons not to implant a SOLO valve were asymmetric commissures (26%) and a large aortic annulus (24%). Only one patient had structural valve deterioration, and none of the patients had to undergo reoperation because of aortic valve insufficiency or paravalvular leakage. Asymmetric commissures, large aortic annulus (>27 mm), calcified aortic sinuses, dilated sinotubular junction, aberrant location of coronary ostia and whenever the stent of a stented bioprosthesis is useful, were contraindications to implant a SOLO valve. When these contraindications were taken into account, a very good durability could be achieved with the SOLO valve during mid-term follow up.

“Partial duplication of lower lip and hemimandible” A rare case

PubMed Central

Nayak, Bibhuti Bhusan; Mohanty, Nilamani

2012-01-01

Duplication of mandible and lower lip is a very rare congenital entity. We report an extremely uncommon case of Congenital Duplication of Lower lip and Mandible in a 3 year old girl, who was treated surgically in a single stage for correction of both lip and mandible. This was a commissure preserving single staged procedure. The Surgical procedure, the problems related to this anomaly and the embryology are discussed. PMID:23450337

Repair of traumatic tricuspid insufficiency via minimally invasive port access.

PubMed

Kasahara, Hirofumi; Kudo, Mikihiko; Kawajiri, Hiroyuki; Yozu, Ryohei

2010-04-01

We report on a successful tricuspid valve plasty using port-access minimally invasive cardiac surgery (MICS) for severe traumatic tricuspid insufficiency caused by blunt chest trauma suffered 15 years previously. A combination repair procedure, consisting of cleft closures, plication of the anteroseptal commissure, and ring annuloplasty, was necessary to achieve valve competence and proved possible via port access without difficulty. Port-access MICS is an alternative approach for tricuspid valve surgery.

Quality-of-life improvement after free gracilis muscle transfer for smile restoration in patients with facial paralysis.

PubMed

Lindsay, Robin W; Bhama, Prabhat; Hadlock, Tessa A

2014-01-01

Facial paralysis can contribute to disfigurement, psychological difficulties, and an inability to convey emotion via facial expression. In patients unable to perform a meaningful smile, free gracilis muscle transfer (FGMT) can often restore smile function. However, little is known about the impact on disease-specific quality of life. To determine quantitatively whether FGMT improves quality of life in patients with facial paralysis. Prospective evaluation of 154 FGMTs performed at a facial nerve center on 148 patients with facial paralysis. The Facial Clinimetric Evaluation (FaCE) survey and Facial Assessment by Computer Evaluation software (FACE-gram) were used to quantify quality-of-life improvement, oral commissure excursion, and symmetry with smile. Free gracilis muscle transfer. Change in FaCE score, oral commissure excursion, and symmetry with smile. There were 127 successful FGMTs on 124 patients and 14 failed procedures on 13 patients. Mean (SD) FaCE score increased significantly after successful FGMT (42.30 [15.9] vs 58.5 [17.60]; paired 2-tailed t test, P < .001). Mean (SD) FACE scores improved significantly in all subgroups (nonflaccid cohort, 37.8 [19.9] vs 52.9 [19.3]; P = .02; flaccid cohort, 43.1 [15.1] vs 59.6 [17.2]; P < .001; trigeminal innervation cohort, 38.9 [14.6] vs 55.2 [18.2]; P < .001; cross-face nerve graft cohort, 47.3 [16.6] vs 61.7 [16.9]; P < .001) except the failure cohort (36.5 [20.8] vs 33.5 [17.9]; Wilcoxon signed-rank test, P = .15). Analysis of 40 patients' photographs revealed a mean (SD) preoperative and postoperative excursion on the affected side of -0.88 (3.79) and 7.68 (3.38), respectively (P < .001); symmetry with smile improved from a mean (SD) of 13.8 (7.46) to 4.88 (3.47) (P < .001). Free gracilis muscle transfer has become a mainstay in the management armamentarium for patients with severe reduction in oral commissure movement after facial nerve insult and recovery. We found a quantitative improvement in quality of life after FGMT in patients who could not recover a meaningful smile after facial nerve insult. Quality-of-life improvement was not statistically different between donor nerve groups or facial paralysis types.

Defining Adverse Outcome Pathways for Effects of the Fungicide Propiconazole of Fish Reproduction

EPA Science Inventory

Adverse outcome pathways (AOPs) are used to describe the linkage of chemical interactions in terms of molecular initiating events to whole organism responses suitable for risk assessment. This study was conducted to develop AOPs for the model fungicide propiconazole relative to r...

Processing of Sequential and Holistic Stimuli in Left and Right Visual Fields,

DTIC Science & Technology

1980-10-01

1 7 A-A091 588 AIR =FORCE ACADEMY CO IF/G 5/10 I PROCESSING OF SEQUENTIAL AND HOLISTIC STIMULI IN LEFT AND RIGHT--ETC( U ) OCT 80 E H GALLUSCIO. D A...neocortical commissures sectioned to reduce grand mal seizures have added significantly to 1.. ... . ....... .......- , l - ’ ’ . .... . .. ’ r U I l...REALISTIC AUTISTIC MASLOW RATIONAL INTUITIVE MILNER VERBAL NON-VERBAL NEISSER SEQUENTIAL MULTIPLE ORNSTEIN ANALYTIC HOLISTIC C. S. PEIRCE EXPLICATIVE

[Convergence nystagmus and vertical gaze palsy of vascular origin].

PubMed

Jouvent, E; Benisty, S; Fenelon, G; Créange, A; Pierrot-Deseilligny, C

2005-05-01

A case of convergence-retraction nystagmus with upward vertical gaze paralysis and skew deviation (right hypotropia), without any other neurological signs, is reported. The probably vascular lesion was located at the mesodiencephalic junction, lying between the right border of the posterior commissure, the right interstitial nucleus of Cajal and the periaqueductal grey matter, accounting for the three ocular motor signs. The particular interest of this case is due to the relative smallness of the lesion.

Multi-tensor investigation of orbitofrontal cortex tracts affected in subcaudate tractotomy.

PubMed

Yang, Jimmy C; Papadimitriou, George; Eckbo, Ryan; Yeterian, Edward H; Liang, Lichen; Dougherty, Darin D; Bouix, Sylvain; Rathi, Yogesh; Shenton, Martha; Kubicki, Marek; Eskandar, Emad N; Makris, Nikos

2015-06-01

Subcaudate tractotomy (SCT) is a neurosurgical lesioning procedure that can reduce symptoms in medically intractable obsessive compulsive disorder (OCD). Due to the putative importance of the orbitofrontal cortex (OFC) in symptomatology, fibers that connect the OFC, SCT lesion, and either the thalamus or brainstem were investigated with two-tensor tractography using an unscented Kalman filter approach. From this dataset, fibers were warped to Montreal Neurological Institute space, and probability maps with center-of-mass analysis were subsequently generated. In comparing fibers from the same OFC region, including medial OFC (mOFC), central OFC (cOFC), and lateral OFC (lOFC), the area of divergence for fibers connected with the thalamus versus the brainstem is posterior to the anterior commissure. At the anterior commissure, fibers connected with the thalamus run dorsal to those connected with the brainstem. As OFC fibers travel through the ventral aspect of the internal capsule, lOFC fibers are dorsal to cOFC and mOFC fibers. Using neuroanatomical comparison, tracts coursing between the OFC and thalamus are likely part of the anterior thalamic radiations, while those between the OFC and brainstem likely belong to the medial forebrain bundle. These data support the involvement of the OFC in OCD and may be relevant to creating differential lesional procedures of specific tracts or to developing deep brain stimulation programming paradigms.

Formation of the spinal network in zebrafish determined by domain-specific Pax genes

PubMed Central

Ikenaga, Takanori; Urban, Jason M.; Gebhart, Nichole; Hatta, Kohei; Kawakami, Koichi; Ono, Fumihito

2012-01-01

In the formation of the spinal network, various transcription factors interact to develop specific cell types. Using a gene trap technique, we established a stable line of zebrafish in which the red fluorescent protein (RFP) was inserted in the pax8 gene. RFP insertion marked putative pax8-lineage cells with fluorescence and inhibited pax8 expression in homozygous embryos. Pax8 homozygous embryos displayed defects in the otic vesicle, as previously reported in studies using morpholinos. The pax8 homozygous embryos survived to adulthood in contrast to mammalian counterparts that die prematurely. RFP is expressed in the dorsal spinal cord. Examination of the axon morphology revealed that RFP (+) neurons include Commissural Bifurcating Longitudinal (CoBL) interneurons, but other inhibitory neurons such as Commissural Local (CoLo) interneurons and Circumferential Ascending (CiA) interneurons do not express RFP. We examined the effect of inhibiting pax2a/pax8 expression on interneuron development. In pax8 homozygous fish, the RFP (+) cells undergo differentiation similar to that of pax8 heterozygous fish, and the swimming behavior remained intact. In contrast, the RFP (+) cells of pax2a/pax8 double mutants displayed altered cell fates. CoBLs were not observed. Instead, RFP (+) cells exhibited axons descending ipsilaterally: a morphology resembling that of V2a/V2b interneurons. PMID:21452218

Formation of the spinal network in zebrafish determined by domain-specific pax genes.

PubMed

Ikenaga, Takanori; Urban, Jason M; Gebhart, Nichole; Hatta, Kohei; Kawakami, Koichi; Ono, Fumihito

2011-06-01

In the formation of the spinal network, various transcription factors interact to develop specific cell types. By using a gene trap technique, we established a stable line of zebrafish in which the red fluorescent protein (RFP) was inserted into the pax8 gene. RFP insertion marked putative pax8-lineage cells with fluorescence and inhibited pax8 expression in homozygous embryos. Pax8 homozygous embryos displayed defects in the otic vesicle, as previously reported in studies with morpholinos. The pax8 homozygous embryos survived to adulthood, in contrast to mammalian counterparts that die prematurely. RFP is expressed in the dorsal spinal cord. Examination of the axon morphology revealed that RFP(+) neurons include commissural bifurcating longitudinal (CoBL) interneurons, but other inhibitory neurons such as commissural local (CoLo) interneurons and circumferential ascending (CiA) interneurons do not express RFP. We examined the effect of inhibiting pax2a/pax8 expression on interneuron development. In pax8 homozygous fish, the RFP(+) cells underwent differentiation similar to that of pax8 heterozygous fish, and the swimming behavior remained intact. In contrast, the RFP(+) cells of pax2a/pax8 double mutants displayed altered cell fates. CoBLs were not observed. Instead, RFP(+) cells exhibited axons descending ipsilaterally, a morphology resembling that of V2a/V2b interneurons. Copyright © 2010 Wiley-Liss, Inc.

Phenotypic Characterization of Speed-Associated Gait Changes in Mice Reveals Modular Organization of Locomotor Networks

PubMed Central

Bellardita, Carmelo; Kiehn, Ole

2015-01-01

SUMMARY Studies of locomotion in mice suggest that circuits controlling the alternating between left and right limbs may have a modular organization with distinct locomotor circuits being recruited at different speeds. It is not clear, however, whether such a modular organization reflects specific behavioral outcomes expressed at different speeds of locomotion. Here, we use detailed kinematic analyses to search for signatures of a modular organization of locomotor circuits in intact and genetically modified mice moving at different speeds of locomotion. We show that wild-type mice display three distinct gaits: two alternating, walk and trot, and one synchronous, bound. Each gait is expressed in distinct ranges of speed with phenotypic inter-limb and intra-limb coordination. A fourth gait, gallop, closely resembled bound in most of the locomotor parameters but expressed diverse inter-limb coordination. Genetic ablation of commissural V0V neurons completely removed the expression of one alternating gait, trot, but left intact walk, gallop, and bound. Ablation of commissural V0V and V0D neurons led to a loss of walk, trot, and gallop, leaving bound as the default gait. Our study provides a benchmark for studies of the neuronal control of locomotion in the full range of speeds. It provides evidence that gait expression depends upon selection of different modules of neuronal ensembles. PMID:25959968

Cross-face nerve grafting for reanimation of incomplete facial paralysis: quantitative outcomes using the FACIAL CLIMA system and patient satisfaction.

PubMed

Hontanilla, Bernardo; Marre, Diego; Cabello, Alvaro

2014-01-01

Although in most cases Bell palsy resolves spontaneously, approximately one-third of patients will present sequela including facial synkinesis and paresis. Currently, the techniques available for reanimation of these patients include hypoglossal nerve transposition, free muscle transfer, and cross-face nerve grafting (CFNG). Between December 2008 and March 2012, eight patients with incomplete unilateral facial paralysis were reanimated with two-stage CFNG. Gender, age at surgery, etiology of paralysis denervation time, donor and recipient nerves, presence of facial synkinesis, and follow-up were registered. Commissural excursion and velocity and patient satisfaction were evaluated with the FACIAL CLIMA and a questionnaire, respectively. Mean age at surgery was 33.8 ± 11.5 years; mean time of denervation was 96.6 ± 109.8 months. No complications requiring surgery were registered. Follow-up period ranged from 7 to 33 months with a mean of 19 ± 9.7 months. FACIAL CLIMA showed improvement of both commissural excursion and velocity greater than 75% in 4 patients, greater than 50% in 2 patients, and less than 50% in the remaining two patients. Qualitative evaluation revealed a high grade of satisfaction in six patients (75%). Two-stage CFNG is a reliable technique for reanimation of incomplete facial paralysis with a high grade of patient satisfaction. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Prevalence of Demodex canis-positive healthy dogs at trichoscopic examination.

PubMed

Fondati, Alessandra; De Lucia, Michela; Furiani, Nicla; Monaco, Moira; Ordeix, Laura; Scarampella, Fabia

2010-04-01

Demodex canis is thought to be present in small numbers in the skin of most healthy dogs; however, available data on the prevalence of normal dogs harbouring D. canis are scarce. The purpose of this study was to investigate, using microscopic examination of plucked hairs, the prevalence of healthy dogs harbouring D. canis. Seventy-eight clinically healthy dogs with no history of dermatological problems and clinically normal skin and hair coat were included in the study. Five areas (perioral skin 2-3mm from both labial commissures, periungual skin of the third digit of both anterior paws and chin) were examined in each dog. Fifty to sixty hairs were plucked from each skin site and microscopically examined. No D. canis mites were observed and only one adult form of Demodex injai was found in the labial commissure of one dog. Based on these results, the estimated prevalence of healthy dogs harbouring D. canis in clinically normal skin should not exceed the threshold of 5.4%, with 95% confidence level. Considering our and previous findings, we propose that, although small numbers of D. canis might inhabit the skin of normal dogs, the probability of finding these mites in normal dogs is low. Consequently, in most cases, the presence of a D. canis mite in the skin should not be considered as indicative of normality.

Shortening of the front vibrating part of the vocal folds in phonation.

PubMed

Pesák, J; Jindra, P

2005-01-01

We have tried to make use of the opportunity of repeated observations through the analysis of the recorded movements of the phonating vocal folds by means of the phonating vocal folds through indirect videolaryngostroboscopic technique. The results of our investigation correspond, among others, with Hála and Sovák's diagrammatic description of continual and gradual changes in the vibration of the vocal folds in an uninterrupted sequence of tones of the human voice. In the initial chapter mention has been made of Hála and Honty's works and of Pressmann's work dealing with the described behaviour of the glottis when phonating high-pitched tones. The conclusions analogous to our findings have also been described by means of stereoscopically measuring the length of the phonating vocal folds. In conclusion, by measuring the distances between the anterior commissure and the junction between the membranous part of the vocal fold and vocal process of the arytenoid and the anterior commissure to the posterior nodal point of the vibrating part of the vocal folds we have verified the correctness of the findings published by Czermak, Hála and Honty, Pressmann, and Sovák, who pointed out the phenomenon of the shortening of the front vibrating part of the vocal folds in phonating high-pitched tones of the human voice. Copyright 2005 S. Karger AG, Basel.

[Lengthening temporalis myoplasty: Technical refinements].

PubMed

Guerreschi, P; Labbé, D

2015-10-01

First described by Labbé in 1997, the lengthening temporalis myoplasty (LTM) ensures the transfer of the entire temporal muscle from the coronoid process to the upper half of the lip without interposition of aponeurotic tissue. Thanks to brain plasticity, the temporal muscle is able to change its function because it is entirely mobilized towards another effector: the labial commissure. After 6 months of speech rehabilitation, the muscle loses its chewing function and it acquires its new smiling function. We describe as far as possible all the technical points to guide surgeons who would like to perform this powerful surgical procedure. We show the coronoid process approaches both through an upper temporal fossa approach and a lower nasolabial fold approach. Rehabilitation starts 3 weeks after the surgery following a standardized protocol to move from a mandibular smile to a voluntary smile, and then a spontaneous smile in 3 steps. The LTM is the main part of a one-stage global treatment of the paralyzed face. It constitutes a dynamic palliative treatment usually started at the sequelae stage, 18 months after the outcome of a peripheral facial paralysis. This one-stage procedure is a reproducible and relevant surgical technique in the difficult treatment of peripheral facial paralysis. An active muscle is transferred to reanimate the labial commissure and to recreate a mobile nasolabial fold. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Network architecture of the cerebral nuclei (basal ganglia) association and commissural connectome.

PubMed

Swanson, Larry W; Sporns, Olaf; Hahn, Joel D

2016-10-04

The cerebral nuclei form the ventral division of the cerebral hemisphere and are thought to play an important role in neural systems controlling somatic movement and motivation. Network analysis was used to define global architectural features of intrinsic cerebral nuclei circuitry in one hemisphere (association connections) and between hemispheres (commissural connections). The analysis was based on more than 4,000 reports of histologically defined axonal connections involving all 45 gray matter regions of the rat cerebral nuclei and revealed the existence of four asymmetrically interconnected modules. The modules form four topographically distinct longitudinal columns that only partly correspond to previous interpretations of cerebral nuclei structure-function organization. The network of connections within and between modules in one hemisphere or the other is quite dense (about 40% of all possible connections), whereas the network of connections between hemispheres is weak and sparse (only about 5% of all possible connections). Particularly highly interconnected regions (rich club and hubs within it) form a topologically continuous band extending through two of the modules. Connection path lengths among numerous pairs of regions, and among some of the network's modules, are relatively long, thus accounting for low global efficiency in network communication. These results provide a starting point for reexamining the connectional organization of the cerebral hemispheres as a whole (right and left cerebral cortex and cerebral nuclei together) and their relation to the rest of the nervous system.

A protocol for identifying suitable biomarkers to assess fish health: A systematic review

PubMed Central

2017-01-01

Background Biomarkers have been used extensively to provide the connection between external levels of contaminant exposure, internal levels of tissue contamination, and early adverse effects in organisms. Objectives To present a three-step protocol for identifying suitable biomarkers to assess fish health in coastal and marine ecosystems, using Gladstone Harbour (Australia) as a case study. Methods Prior to applying our protocol, clear working definitions for biomarkers were developed to ensure consistency with the global literature on fish health assessment. First, contaminants of concern were identified based on the presence of point and diffuse sources of pollution and available monitoring data for the ecosystem of interest. Second, suitable fish species were identified using fisheries dependent and independent data, and prioritised based on potential pathways of exposure to the contaminants of concern. Finally, a systematic and critical literature review was conducted on the use of biomarkers to assess the health of fish exposed to the contaminants of concern. Results/Discussion We present clear working definitions for bioaccumulation markers, biomarkers of exposure, biomarkers of effect and biomarkers of susceptibility. Based on emission and concentration information, seven metals were identified as contaminants of concern for Gladstone Harbour. Twenty out of 232 fish species were abundant enough to be potentially suitable for biomarker studies; five of these were prioritised based on potential pathways of exposure and susceptibility to metals. The literature search on biomarkers yielded 5,035 articles, of which 151met the inclusion criteria. Based on our review, the most suitable biomarkers include bioaccumulation markers, biomarkers of exposure (CYP1A, EROD, SOD, LPOX, HSP, MT, DNA strand breaks, micronuclei, apoptosis), and biomarkers of effect (histopathology, TAG:ST). Conclusion Our protocol outlines a clear pathway to identify suitable biomarkers to assess fish health in coastal and marine ecosystems, which can be applied to biomarker studies in aquatic ecosystems around the world. PMID:28403149

Effects of image distortions originating from susceptibility variations and concomitant fields on diffusion MRI tractography results

PubMed Central

Irfanoglu, M. Okan; Walker, Lindsay; Sarlls, Joelle; Marenco, Stefano; Pierpaoli, Carlo

2013-01-01

In this work we investigate the effects of echo planar imaging (EPI) distortions on diffusion tensor imaging (DTI) based fiber tractography results. We propose a simple experimental framework that would enable assessing the effects of EPI distortions on the accuracy and reproducibility of fiber tractography from a pilot study on a few subjects. We compare trajectories computed from two diffusion datasets collected on each subject that are identical except for the orientation of phase encode direction, either right–left (RL) or anterior–posterior (AP). We define metrics to assess potential discrepancies between RL and AP trajectories in association, commissural, and projection pathways. Results from measurements on a 3 Tesla clinical scanner indicated that the effects of EPI distortions on computed fiber trajectories are statistically significant and large in magnitude, potentially leading to erroneous inferences about brain connectivity. The correction of EPI distortion using an image-based registration approach showed a significant improvement in tract consistency and accuracy. Although obtained in the context of a DTI experiment, our findings are generally applicable to all EPI-based diffusion MRI tractography investigations, including high angular resolution (HARDI) methods. On the basis of our findings, we recommend adding an EPI distortion correction step to the diffusion MRI processing pipeline if the output is to be used for fiber tractography. PMID:22401760

The nervus terminalis in larval and adult Xenopus laevis.

PubMed

Hofmann, M H; Meyer, D L

1989-09-25

Nervus terminalis (nt) projections were studied by HRP injections into one nostril in adult Xenopus and in Xenopus tadpoles. Central nt targets are: medial septum, preoptic nucleus, nucleus of the anterior commissure, and hypothalamus (mainly ipsilaterally). In Xenopus tadpoles, additional fibers reach the ipsilateral dorsal thalamus and the mesencephalic tegmentum, bilaterally; furthermore, hypothalamic projections are bilateral. Xenopus tadpole nt connections resemble those of adult urodeles more closely than the projections of frogs. However, Xenopus tadpoles lack nt innervation of the medial septum.

Building blocks of a fish head: Developmental and variational modularity in a complex system.

PubMed

Lehoux, Caroline; Cloutier, Richard

2015-11-01

Evolution of the vertebrate skull is developmentally constrained by the interactions among its anatomical systems, such as the dermatocranium and the sensory system. The interaction between the dermal bones and lateral line canals has been debated for decades but their morphological integration has never been tested. An ontogenetic series of 97 juvenile and adult Amia calva (Actinopterygii) was used to describe the patterning and modularity of sensory lateral line canals and their integration with supporting cranial bones. Developmental modules were tested for the otic canal and supratemporal commissure by computing correlations in the branching sequence of groups of pores. Landmarks were digitized on 25 specimens to test a priori hypotheses of variational and developmental modularity at the level of canals and dermal bones. Branching sequence suggests a specific patterning supported by significant positive correlations in the sequence of appearance of branches between bilateral sides. Differences in patterning between the otic canal and the supratemporal commissure and tests of modularity with geometric morphometrics suggest that both canals form distinct modules. The integration between bones and canals was insufficient to detect a module. However, both components were not independent. Groups of pores tended to disappear without affecting other groups of pores suggesting that they are quasi-independent units acting as modules. This study provides evidence of a hierarchical organization for the modular sensory system that could explain variation of pattern of canals among species and their association with dermal bones. © 2015 Wiley Periodicals, Inc.

Identification of the kainate receptor subunits underlying modulation of excitatory synaptic transmission in the CA3 region of the hippocampus.

PubMed

Contractor, A; Swanson, G T; Sailer, A; O'Gorman, S; Heinemann, S F

2000-11-15

To understand the physiological role of kainate receptors and their participation in seizure induction in animal models of epilepsy, it will be necessary to develop a comprehensive description of their action in the CA3 region of the hippocampus. Activation of presynaptic kainate receptors depresses excitatory synaptic transmission at mossy fiber and associational-commissural inputs to CA3 pyramidal neurons (Vignes et al., 1998; Bortolotto et al., 1999; Kamiya and Ozawa, 2000). In this study, we use gene-targeted mice lacking glutamate receptor 5 (GluR5) or GluR6 kainate receptor subunits to identify the receptor subunits that comprise the kainate receptors responsible for presynaptic modulation of CA3 transmission. We found that bath application of kainate (3 microm) profoundly reduced EPSCs at mossy fiber and collateral synapses in neurons from wild-type and GluR5(-/-) mice but had no effect on EPSCs in neurons from GluR6(-/-) mice. These results therefore contrast with previous studies that supported a role for GluR5-containing receptors at mossy fiber and associational-commissural synapses (Vignes et al., 1998; Bortolotto et al., 1999). Surprisingly, at perforant path synapses kainate receptor activation enhanced transmission; this potentiation was abolished in both GluR5 and GluR6 knock-out mice. Kainate receptors thus play multiple and complex roles to modulate excitatory synaptic transmission in the CA3 region of the hippocampus.

Estimating Accurate Target Coordinates with Magnetic Resonance Images by Using Multiple Phase-Encoding Directions during Acquisition.

PubMed

Kim, Minsoo; Jung, Na Young; Park, Chang Kyu; Chang, Won Seok; Jung, Hyun Ho; Chang, Jin Woo

2018-06-01

Stereotactic procedures are image guided, often using magnetic resonance (MR) images limited by image distortion, which may influence targets for stereotactic procedures. The aim of this work was to assess methods of identifying target coordinates for stereotactic procedures with MR in multiple phase-encoding directions. In 30 patients undergoing deep brain stimulation, we acquired 5 image sets: stereotactic brain computed tomography (CT), T2-weighted images (T2WI), and T1WI in both right-to-left (RL) and anterior-to-posterior (AP) phase-encoding directions. Using CT coordinates as a reference, we analyzed anterior commissure and posterior commissure coordinates to identify any distortion relating to phase-encoding direction. Compared with CT coordinates, RL-directed images had more positive x-axis values (0.51 mm in T1WI, 0.58 mm in T2WI). AP-directed images had more negative y-axis values (0.44 mm in T1WI, 0.59 mm in T2WI). We adopted 2 methods to predict CT coordinates with MR image sets: parallel translation and selective choice of axes according to phase-encoding direction. Both were equally effective at predicting CT coordinates using only MR; however, the latter may be easier to use in clinical settings. Acquiring MR in multiple phase-encoding directions and selecting axes according to the phase-encoding direction allows identification of more accurate coordinates for stereotactic procedures. © 2018 S. Karger AG, Basel.

Development of the Neurochemical Architecture of the Central Complex

PubMed Central

Boyan, George S.; Liu, Yu

2016-01-01

The central complex represents one of the most conspicuous neuroarchitectures to be found in the insect brain and regulates a wide repertoire of behaviors including locomotion, stridulation, spatial orientation and spatial memory. In this review article, we show that in the grasshopper, a model insect system, the intricate wiring of the fan-shaped body (FB) begins early in embryogenesis when axons from the first progeny of four protocerebral stem cells (called W, X, Y, Z, respectively) in each brain hemisphere establish a set of tracts to the primary commissural system. Decussation of subsets of commissural neurons at stereotypic locations across the brain midline then establishes a columnar neuroarchitecture in the FB which is completed during embryogenesis. Examination of the expression patterns of various neurochemicals in the central complex including neuropeptides, a neurotransmitter and the gas nitric oxide (NO), show that these appear progressively and in a substance-specific manner during embryogenesis. Each neuroactive substance is expressed by neurons located at stereotypic locations in a given central complex lineage, confirming that the stem cells are biochemically multipotent. The organization of axons expressing the various neurochemicals within the central complex is topologically related to the location, and hence birthdate, of the neurons within the lineages. The neurochemical expression patterns within the FB are layered, and so reflect the temporal topology present in the lineages. This principle relates the neuroanatomical to the neurochemical architecture of the central complex and so may provide insights into the development of adaptive behaviors. PMID:27630548

Diffusion tensor imaging of anterior commissural fibers in patients with schizophrenia.

PubMed

Choi, Hongyoon; Kubicki, Marek; Whitford, Thomas J; Alvarado, Jorge L; Terry, Douglas P; Niznikiewicz, Margaret; McCarley, Robert W; Kwon, Jun Soo; Shenton, Martha E

2011-08-01

Alterations in white matter connections in schizophrenia have been investigated using diffusion tensor imaging (DTI). There is also evidence from post-mortem studies as well as from magnetic resonance imaging morphometry studies that the anterior commissure (AC) might be implicated in schizophrenia, but no studies, to date, have investigated the AC using DTI or tractography. DTI scans were analyzed from 25 patients and 23 controls. Mean fractional anisotropy (FA) and trace were measured from the AC tracts. SANS and SAPS were used to evaluate clinical symptoms, and the Iowa Gambling Task, related to decision making, was also examined. Results revealed a significant decrease in mean FA and a significant increase in mean trace of AC tracts in patients compared with controls. In addition, patients, but not controls, showed a negative correlation between age and AC integrity. Statistically significant positive correlations were also found between AC FA and total positive symptom score. Decision making was negatively correlated with FA in patients on the Iowa Gambling Task, but not in controls. This study provides quantitative evidence for a reduction of interhemispheric connectivity in schizophrenia within the AC. Negative correlation between age and AC FA in the patients is consistent with the idea that schizophrenia may be a disorder of white matter maturation. Positive correlation between FA and positive symptom is discussed in the context of white matter's established role in modulating neural conduction velocity. Published by Elsevier B.V.

Network architecture of the cerebral nuclei (basal ganglia) association and commissural connectome

PubMed Central

Swanson, Larry W.; Sporns, Olaf; Hahn, Joel D.

2016-01-01

The cerebral nuclei form the ventral division of the cerebral hemisphere and are thought to play an important role in neural systems controlling somatic movement and motivation. Network analysis was used to define global architectural features of intrinsic cerebral nuclei circuitry in one hemisphere (association connections) and between hemispheres (commissural connections). The analysis was based on more than 4,000 reports of histologically defined axonal connections involving all 45 gray matter regions of the rat cerebral nuclei and revealed the existence of four asymmetrically interconnected modules. The modules form four topographically distinct longitudinal columns that only partly correspond to previous interpretations of cerebral nuclei structure–function organization. The network of connections within and between modules in one hemisphere or the other is quite dense (about 40% of all possible connections), whereas the network of connections between hemispheres is weak and sparse (only about 5% of all possible connections). Particularly highly interconnected regions (rich club and hubs within it) form a topologically continuous band extending through two of the modules. Connection path lengths among numerous pairs of regions, and among some of the network’s modules, are relatively long, thus accounting for low global efficiency in network communication. These results provide a starting point for reexamining the connectional organization of the cerebral hemispheres as a whole (right and left cerebral cortex and cerebral nuclei together) and their relation to the rest of the nervous system. PMID:27647882

Mechanisms of tricuspid regurgitation in patients with hypoplastic left heart syndrome undergoing tricuspid valvuloplasty.

PubMed

Bautista-Hernandez, Victor; Brown, David W; Loyola, Hugo; Myers, Patrick O; Borisuk, Michele; del Nido, Pedro J; Baird, Christopher W

2014-09-01

Tricuspid regurgitation (TR) remains a risk factor for morbidity and mortality through staged palliation in patients with hypoplastic left heart syndrome (HLHS). Reports on the mechanisms associated with TR in patients with HLHS are limited. Thus, we sought to describe our experience with tricuspid valve (TV) repair in these patients, focusing on the mechanisms of TR and corresponding surgical techniques. We performed a retrospective single-center review (January 2000 to December 2012) of patients with HLHS undergoing TV repair and completing Fontan circulation. We evaluated the pre- and postoperative echocardiograms, intraoperative findings, and surgical techniques used. A total of 53 TV repairs were performed in 35 patients with HLHS completing staged palliation. TV repairs were performed at stage II in 15, between stage II and III in 4, at stage III in 27, and after stage III in 7. The surgical techniques for valvuloplasty included annuloplasty (38%), anteroseptal (AS) commissuroplasty (66%), anterior papillary muscle repositioning (11%), multiple commissuroplasties (9%), septal-posterior commissuroplasty (9%), and fenestration closure (4%). The predominant jet of TR emanated along the AS commissure in 68% of the cases. All patients survived the procedure and were discharged. Preoperative echocardiography showed a dilated TV annulus on the lateral dimension, anteroposterior dimension, and area that was significantly reduced after TV repair (P < .0001). The preoperative mean TR, as assessed by lateral (P = .002) and anteroposterior (P = .005) vena contracta, was also significantly reduced after TV repair. TV repair did not significantly affect right ventricular systolic function immediately after surgery (P = .17) or at the most recent follow-up visit (P = .52). Patients with anterior leaflet prolapse were at increased risk of worse outcomes, including moderate or greater right ventricular dysfunction (P = .02). Patients requiring reoperation for TV repair were younger (6.3 vs 28.1 months, P < .0001) at the initial operation. One patient died of heart failure. Freedom from TV replacement and transplant-free survival were both 97% at the most recent follow-up point. TR in patients with HLHS commonly emanates from the AS commissure. The associated mechanisms are often annular dilatation and anterior leaflet prolapse. Preoperative anterior leaflet prolapse was associated with worse outcomes. Annuloplasty, closure of the AS commissure, and repositioning of the anterior papillary muscle are effective in addressing TR in the short- and mid-term in this challenging population. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Brain Responses and Information Processing I. Hemispheric Asymmetries in Event Related Potentials during Signal Detection.

DTIC Science & Technology

1980-11-30

commissures). Figure 1 illustrates this conceptual model . Poffenberger (1912) was the first to use the RT approach to estimate interhemispheric...neutral densilty filter of 1.0 was placed over the shutter to reduce the flash intensity. Two other filters of 0.1 and 0.3 were used to equalize light...intensity in the three visual fields. 14 cEOɘC CLi Q) L0X LLL 0 4-) E L) Ln u- 15 The electroencephalogram (EEG) was recorded on a Grass Model 78

Ulcerative cheilitis in a rhesus macaque.

PubMed

Bailey, C C; Miller, A D

2012-03-01

A 2-year-old, female, simian immunodeficiency virus E543-infected rhesus macaque (Macaca mulatta) was presented for necropsy following euthanasia due to a history of diarrhea, weight loss, and a small, round ulcer along the left labial commissure. Histopathologic examination of the ulcer revealed infiltration by large numbers of degenerate and nondegenerate neutrophils and macrophages admixed with syncytial epithelial cells. Rare epithelial cells contained herpetic inclusion bodies. These cells stained positive for Human herpesvirus 1 via immunohistochemistry, and DNA sequencing confirmed the presence of closely related Macacine herpesvirus 1 (B virus).

Appropriateness of cases presenting in the emergency department following ambulance service secondary telephone triage: a retrospective cohort study

PubMed Central

Eastwood, Kathryn; Smith, Karen; Morgans, Amee; Stoelwinder, Johannes

2017-01-01

Objective To investigate the appropriateness of cases presenting to the emergency department (ED) following ambulance-based secondary telephone triage. Design A pragmatic retrospective cohort analysis of all the planned and unplanned ED presentations within 48 hours of a secondary telephone triage. Setting The secondary telephone triage service, called the Referral Service, and the hospitals were located in metropolitan Melbourne, Australia and operated 24 hours a day, servicing 4.25 million people. The Referral Service provides an in-depth secondary triage of cases classified as low acuity when calling the Australian emergency telephone number. Population Cases triaged by the Referral Service between September 2009 and June 2012 were linked to ED and hospital admission records (N=44,523). Planned ED presentations were cases referred to the ED following the secondary triage, unplanned ED presentations were cases that presented despite being referred to alternative care pathways. Main outcome measures Appropriateness was measured using an ED suitability definition and hospital admission rates. These were compared with mean population data which consisted of all of the ED presentations for the state (termed the ‘average Victorian ED presentation’). Results Planned ED presentations were more likely to be ED suitable than unplanned ED presentations (OR 1.62; 95% CI 1.5 to 1.7; p<0.001) and the average Victorian ED presentation (OR 1.85; 95% CI 1.01 to 3.4; p=0.046). They were also more likely to be admitted to the hospital than the unplanned ED presentation (OR 1.5; 95% CI 1.4 to 1.6; p<0.001) and the average Victorian ED presentation (OR 2.3, 95% CI 2.24 to 2.33; p<0.001). Just under 15% of cases diverted away from the emergency care pathways presented in the ED (unplanned ED attendances), and 9.5% of all the alternative care pathway cases were classified as ED suitable and 6.5% were admitted to hospital. Conclusions Secondary telephone triage was able to appropriately identify many ED suitable cases, and while most cases referred to alternative care pathways did not present in the ED. Further research is required to establish that these were not inappropriately triaged away from the emergency care pathways. PMID:29038180

Zinc release from Schaffer collaterals and its significance.

PubMed

Takeda, Atsushi; Nakajima, Satoko; Fuke, Sayuri; Sakurada, Naomi; Minami, Akira; Oku, Naoto

2006-02-15

On the basis of the evidence that approximately 45% of Schaffer collateral boutons are zinc-positive, zinc release from Schaffer collaterals and its action were examined in hippocampal slices. When zinc release from Schaffer collaterals was examined using ZnAF-2, a membrane-impermeable zinc indicator, ZnAF-2 signal in the stratum radiatum of the CA1 was increased by tetanic stimuli at 100 Hz for 1s, suggesting that zinc is released from Schaffer collaterals in a calcium- and impulse-dependent manner. An in vivo microdialysis experiment indicated that the perfusion with 10 microM zinc significantly decreases extracellular glutamate concentration in the CA1. When tetanic stimuli at 100 Hz for 5s were delivered to the dentate granule cells, the increase in calcium signal in the stratum radiatum of the CA1, as well as in the stratum lucidum of the CA3, was attenuated by addition of 10 microM zinc, while enhanced by addition of 1mM CaEDTA, a membrane-impermeable zinc chelator. The increase in calcium signal in the CA1, in which Schaffer collateral synapses exist, during delivery of tetanic stimuli at 100 Hz for 1s to the Schaffer collateral-commissural pathway was also significantly enhanced by addition of 1mM CaEDTA. These results suggest that zinc released from Schaffer collaterals suppressively modulates presynaptic and postsynaptic calcium signaling in the CA1, followed by the suppression of glutamate release.

Three-dimensional topographic fiber tract anatomy of the cerebrum.

PubMed

Yagmurlu, Kaan; Vlasak, Alexander L; Rhoton, Albert L

2015-06-01

The fiber tracts of the cerebrum may be a more important determinant of resection limits than the cortex. Better knowledge of the 3-dimensional (3-D) anatomic organization of the fiber pathways is important in planning safe and accurate surgery for lesions within the cerebrum. To examine the topographic anatomy of fiber tracts and subcortical gray matter of the human cerebrum and their relationships with consistent cortical, ventricular, and nuclear landmarks. Twenty-five formalin-fixed human brains and 4 whole cadaveric heads were examined by fiber dissection technique and ×6 to ×40 magnification. The fiber tracts and central core structures, including the insula and basal ganglia, were examined and their relationships captured in 3-D photography. The depth between the surface of the cortical gyri and selected fiber tracts was measured. The topographic relationships of the important association, projection, and commissural fasciculi within the cerebrum and superficial cortical landmarks were identified. Important landmarks with consistent relationships to the fiber tracts were the cortical gyri and sulci, limiting sulci of the insula, nuclear masses in the central core, and lateral ventricles. The fiber tracts were also organized in a consistent pattern in relation to each other. The anatomic findings are briefly compared with functional data from clinicoradiological analysis and intraoperative stimulation of fiber tracts. An understanding of the 3-D anatomic organization of the fiber tracts of the brain is essential in planning safe and accurate cerebral surgery.

Choice of Insulin in Type 2 Diabetes: A Southeast Asian Perspective.

PubMed

Kalra, Sanjay; Thai, Hong Quang; Deerochanawong, Chaicharn; Su-Yen, Goh; Mohamed, Mafauzy; Latt, Tint Swe; Aye, Than Than; Latif, Zafar Ahmed; Katulanda, Prasad; Khun, Touch; Satha, Sum; Vongvandy, Vadsana

2017-01-01

Southeast Asia faces a diabetes epidemic, which has created significant challenges for health care. The unique Asian diabetes phenotype, coupled with peculiar lifestyle, diet, and healthcare-seeking behavior, makes it imperative to develop clinical pathways and guidelines which address local needs and requirements. From an insulin-centric viewpoint, the preparations prescribed in such pathways should be effective, safe, well tolerated, nonintrusive, and suitable for the use in multiple clinical situations including initiation and intensification. This brief communication describes the utility of premixed or dual action insulin in such clinical pathways and guidelines.

New graft sizing rings for aortic valve reimplantation procedures.

PubMed

Jelenc, Matija; Jelenc, Blaž; Kneževic, Ivan; Klokocovnik, Tomislav

2018-01-01

The objective was to design sizing rings that would enable proper sizing of the graft in reimplantation procedures and to perform leaflet repair before graft implantation. The rings were designed in Autodesk Fusion 360 (San Rafael, CA, USA) and 3D printed using a commercial online 3D printing service. We designed incomplete rings with a low profile and complete rings with a high profile. The complete rings are best suited for reimplantation procedures, whereas low profile C rings are intended for isolated aortic valve repair, where the ascending aorta is not transected. The rings come in sizes corresponding to Vascutek Gelweave graft sizes (Vascutek Terumo, Renfrewshire, Scotland). The ring internal diameters are 5% larger than the designated ring sizes and account for the 5% stretch of the grafts when pressurized. Blades of the rings are placed at 20° intervals. The slits between the blades are designed in such a way that the commissural U-sutures, when put in place and under tension, will lock the ring in position. The rings were successfully used in 10 of our latest reimplantation procedures. After dissection of the aortic root, the commissures were suspended with U-stitches and then the ring was seated onto them. Complete leaflet repair with plication to achieve adequate effective height was then performed, followed by graft implantation. No additional leaflet repair was needed. The newly designed sizing rings enable proper sizing of the graft in reimplantation procedures and enable complete leaflet repair before graft implantation. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Properties of vestibular neurones projecting to neck segments of the cat spinal cord*

PubMed Central

Rapoport, S.; Susswein, A.; Uchino, Y.; Wilson, V. J.

1977-01-01

1. Vestibular neurones projecting to the upper cervical grey matter (vestibulocollic neurones) were identified by localized microstimulation in the C3 segment of the cat spinal cord. 2. The neurones were found in the lateral (Deiters'), medial and descending nuclei bilaterally and projected to the spinal cord in the lateral and medial vestibulospinal tracts (LVST and MVST). Ipsilateral axons of Deiters' neurones were mostly in the LVST, axons of medial and descending neurones in the MVST; a few Deiters' neurones had axons in the MVST; some descending neurones had axons in the LVST. Most axons of contralateral neurones were in the MVST. 3. The axons of 62% of ipsilateral vestibulocollic Deiters' neurones not only gave off a collateral to C3, but also extended as far as the cervical enlargement (`branching'); some of these neurones projected as far as the upper thoracic cord, almost none to the lumbar cord. Ipsilateral descending nucleus neurones branch in the same fashion, but there is no branching in the relatively small medial nucleus population. 4. A large majority of vestibulocollic neurones receive monosynaptic excitation from the ipsilateral labyrinth and a number are inhibited by stimulation of the contralateral labyrinth (commissural inhibition). It is possible that commissural inhibition acts on a broad population of vestibular neurones involved in the control of eye, head and trunk movement. 5. Vestibulocollic neurones do not make up a homogeneous population acting only on the neck. Instead it is likely that subpopulations, for example branching and non-branching neurones, have different functions. PMID:874918

Comparative study of smile analysis by subjective and computerized methods.

PubMed

Basting, Roberta Tarkany; da Trindade, Rita de Cássia Silva; Flório, Flávia Martão

2006-01-01

This study compared: 1) the subjective analyses of a smile done by specialists with advanced training and by general dentists; 2) the subjective analysis of a smile, or that associated with the face, by specialists with advanced training and general dentists; 3) subjective analysis using a computerized analysis of the smile by specialists with advanced training, verifying the midline, labial line, smile line, the line between commissures and the golden proportion. The sample consisted of 100 adults with natural dentition; 200 photographs were taken (100 of the smile and 100 of the entire face). Computerized analysis using AutoCAD software was performed, together with the subjective analyses of 2 groups of professionals (3 general dentists and 3 specialists with advanced training), using the following assessment factors: the midline, labial line, smile line, line between the commissures and the golden proportion. The smile itself and the smile associated with the entire face were recorded as being agreeable or not agreeable by the professionals. The McNemar test showed a highly significant difference (p=0.0000) among the subjective analyses performed by specialists compared to general dentists. Between the 2 groups of dental professionals, there were highly significant differences (p=0.0000) found between the subjective analyses of the smile and that of the face. The McNemar test showed statistical differences in all factors assessed, with the exception of the midline (p=0.1951), when the computerized analysis and subjective analysis of the specialists were compared. In order to establish harmony of the smile, it was not possible to establish a greater or lesser relevance among the factors analyzed.

Establishment of a new relationship between posed smile width and lower facial height: A cross-sectional study

PubMed Central

Abraham, Aby; George, Jinu; Peter, Elbe; Philip, Koshi; Chankramath, Rajesh; Johns, Dexton Antony; Bhaskar, Anitha

2015-01-01

Objective: The present study is intended to add a new parameter that would be useful in orthodontic clinical evaluation, treatment planning, and determination of vertical dimension (at occlusion). Materials and Methods: Standardized videographic recording of 79 subjects during posed smile was captured. Each video was then cut into 30 photos using the free studio software. The widest commissure-to-commissure posed smile frame (posed smile width [SW]) was selected as one of 10 or more frames showing an identical smile. Lower third of the face is measured from subnasale to soft tissue menton using a digital vernier caliper. Two values were then compared. Ratio between lower facial height and posed SW was calculated. Results: The co-relation between smiling width and lower facial height was found to be statistically significant (P < 0.01). The ratio of lower facial height and smiling width was calculated as 1.0016 with a standard deviation (SD) = 0.04 in males and 1.0301 with an SD = 0.07 in females. The difference between the mean lower facial height in males and females was statistically significant with a t = 10.231 and P = 0.000. The difference between the mean smiling width in males and females was also statistically significant with a t = 5.653 and P = 0.000. Conclusion: In class I subjects with pleasing appearance, normal facial proportions, normal overjet and overbite, and average Frankfort mandibular angle, the lower facial height (subnasale to soft tissue menton) is equal to posed SW. PMID:26430369

Comprehensive 4-stage categorization of bicuspid aortic valve leaflet morphology by cardiac MRI in 386 patients.

PubMed

Murphy, I G; Collins, J; Powell, A; Markl, M; McCarthy, P; Malaisrie, S C; Carr, J C; Barker, A J

2017-08-01

Bicuspid aortic valve (BAV) disease is heterogeneous and related to valve dysfunction and aortopathy. Appropriate follow up and surveillance of patients with BAV may depend on correct phenotypic categorization. There are multiple classification schemes, however a need exists to comprehensively capture commissure fusion, leaflet asymmetry, and valve orifice orientation. Our aim was to develop a BAV classification scheme for use at MRI to ascertain the frequency of different phenotypes and the consistency of BAV classification. The BAV classification scheme builds on the Sievers surgical BAV classification, adding valve orifice orientation, partial leaflet fusion and leaflet asymmetry. A single observer successfully applied this classification to 386 of 398 Cardiac MRI studies. Repeatability of categorization was ascertained with intraobserver and interobserver kappa scores. Sensitivity and specificity of MRI findings was determined from operative reports, where available. Fusion of the right and left leaflets accounted for over half of all cases. Partial leaflet fusion was seen in 46% of patients. Good interobserver agreement was seen for orientation of the valve opening (κ = 0.90), type (κ = 0.72) and presence of partial fusion (κ = 0.83, p < 0.0001). Retrospective review of operative notes showed sensitivity and specificity for orientation (90, 93%) and for Sievers type (73, 87%). The proposed BAV classification schema was assessed by MRI for its reliability to classify valve morphology in addition to illustrating the wide heterogeneity of leaflet size, orifice orientation, and commissural fusion. The classification may be helpful in further understanding the relationship between valve morphology, flow derangement and aortopathy.

Netrin1 establishes multiple boundaries for axon growth in the developing spinal cord.

PubMed

Varadarajan, Supraja G; Butler, Samantha J

2017-10-01

The canonical model for netrin1 function proposed that it acted as a long-range chemotropic axon guidance cue. In the developing spinal cord, floor-plate (FP)-derived netrin1 was thought to act as a diffusible attractant to draw commissural axons to the ventral midline. However, our recent studies have shown that netrin1 is dispensable in the FP for axon guidance. We have rather found that netrin1 acts locally: netrin1 is produced by neural progenitor cells (NPCs) in the ventricular zone (VZ), and deposited on the pial surface as a haptotactic adhesive substrate that guides Dcc + axon growth. Here, we further demonstrate that this netrin1 pial-substrate has an early role orienting pioneering spinal axons, directing them to extend ventrally. However, as development proceeds, commissural axons choose to grow around a boundary of netrin1 expressing cells in VZ, instead of continuing to extend alongside the netrin1 pial-substrate in the ventral spinal cord. This observation suggests netrin1 may supply a more complex activity than pure adhesion, with netrin1-expressing cells also supplying a growth boundary for axons. Supporting this possibility, we have observed that additional domains of netrin1 expression arise adjacent to the dorsal root entry zone (DREZ) in E12.5 mice that are also required to sculpt axonal growth. Together, our studies suggest that netrin1 provides "hederal" boundaries: a local growth substrate that promotes axon extension, while also preventing local innervation of netrin1-expressing domains. Copyright © 2017 Elsevier Inc. All rights reserved.

Masseteric-facial nerve transposition for reanimation of the smile in incomplete facial paralysis.

PubMed

Hontanilla, Bernardo; Marre, Diego

2015-12-01

Incomplete facial paralysis occurs in about a third of patients with Bell's palsy. Although their faces are symmetrical at rest, when they smile they have varying degrees of disfigurement. Currently, cross-face nerve grafting is one of the most useful techniques for reanimation. Transfer of the masseteric nerve, although widely used for complete paralysis, has not to our knowledge been reported for incomplete palsy. Between December 2008 and November 2013, we reanimated the faces of 9 patients (2 men and 7 women) with incomplete unilateral facial paralysis with transposition of the masseteric nerve. Sex, age at operation, cause of paralysis, duration of denervation, recipient nerves used, and duration of follow-up were recorded. Commissural excursion, velocity, and patients' satisfaction were evaluated with the FACIAL CLIMA and a questionnaire, respectively. The mean (SD) age at operation was 39 (±6) years and the duration of denervation was 29 (±19) months. There were no complications that required further intervention. Duration of follow-up ranged from 6-26 months. FACIAL CLIMA showed improvement in both commissural excursion and velocity of more than two thirds in 6 patients, more than one half in 2 patients and less than one half in one. Qualitative evaluation showed a slight or pronounced improvement in 7/9 patients. The masseteric nerve is a reliable alternative for reanimation of the smile in patients with incomplete facial paralysis. Its main advantages include its consistent anatomy, a one-stage operation, and low morbidity at the donor site. Copyright © 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Transcatheter Treatment of Tricuspid Regurgitation Using Edge-to-Edge Repair: Procedural Results, Clinical Implications and Predictors for Success.

PubMed

Lurz, Philipp; Besler, Christian; Noack, Thilo; Forner, Anna Flo; Bevilacqua, Carmine; Seeburger, Joerg; Rommel, Karl-Philipp; Blazek, Stephan; Hartung, Philipp; Zimmer, Marion; Mohr, Friedrich; Schuler, Gerhard; Linke, Axel; Ender, Joerg; Thiele, Holger

2018-04-10

To analyze the feasibility, safety and effectiveness of Tricuspid valve (TV) repair using the MitraClip system in patients at high surgical risk. Forty-two elderly high-risk patients (76.8±7.3 years, EuroScore II 8.1±5.7) with isolated TR or combined TR and mitral regurgitation (MR) underwent edge-to-edge repair of the TV (n=11) or combined edge-to-edge repair of the TV and mitral valve (n=31). Procedural details, success rate, impact on TR severity and predictors for success at 30 day follow-up were analyzed. Successful edge-to-edge repair of TR was achieved in 35/42 patients (83%, 68 clips in total, 94% in the anteroseptal commissure, 6% in the posteroseptal commissure). In 5 patients, grasping of the leaflets was impossible and two patients had no decrease in TR after clipping. In those with procedural success, clipping of the TV led to a reduction in effective regurgitant orifice area by -62,5 % (from 0.8±0.4 to 0.3±0.2 cm2; p<0.0001). In both, patients with isolated TV and combined procedures, 6 minute walking distance improved (from 285±118 to 344±81 and 225±113 to 261±130 m, p=0.02 and 0.03, respectively). Predominant anteroseptal or central TR was identified as predictor of procedural success (p=0.025). Edge-to-edge repair of the TV is feasible with promising reduction in TR, which could result in clinical improvement.

Three-Dimensional Anatomy of the White Matter Fibers of the Temporal Lobe: Surgical Implications.

PubMed

Pescatori, Lorenzo; Tropeano, Maria Pia; Manfreda, Andrea; Delfini, Roberto; Santoro, Antonio

2017-04-01

The aim of this work is to describe in detail the complex 3-dimensional organization of the white matter of the temporal lobe and discuss the surgical implications of the approaches to lesions located into the mesial temporal region and within the temporal horn and the atrium of the lateral ventricles. Sixteen human cerebral hemispheres fixed in a 10% formalin solution for at least 40 days were studied. After removal of the arachnoid membrane, the hemispheres were frozen at -15°C for at least 14 days, and the Klingler technique, which consists of the microscopic dissection and progressive identification of white matter fibers, was performed. The dissection allowed us to appreciate the topographical organization of the white matter of the temporal lobe identifying the most important association, projection, and commissural fasciculi. The dissection from the lateral side allowed the progressive visualization of the superior longitudinal fasciculus and its components, the extreme and external capsule, the uncinate fasciculus, the inferior fronto-occipital fasciculus, the anterior commissure, the internal capsule, and the optic radiations. The dissection was completed from the inferior and medial side for identification of the cingulum and the fornix. The complex 3-dimensional organization of the white matter substance of the temporal lobe is characterized by 2 main systems of boundaries: the sagittal stratum and the temporal stem. Their knowledge is essential for the appropriate treatment of pathologies localized in this region as demonstrated by the 2 clinical cases presented in this work. Copyright © 2017 Elsevier Inc. All rights reserved.

Stress Analysis of Transcatheter Aortic Valve Leaflets Under Dynamic Loading: Effect of Reduced Tissue Thickness.

PubMed

Abbasi, Mostafa; Azadani, Ali N

2017-07-01

In order to accommodate transcatheter valves to miniaturized catheters, the leaflet thickness must be reduced to a value which is typically less than that of surgical bioprostheses. The study aim was to use finite-element simulations to determine the impact of the thickness reduction on stress and strain distribution. A 23 mm transcatheter aortic valve (TAV) was modelled based on the Edwards SAPIEN XT (Edwards Lifesciences, Irvine, CA, USA). Finite-element (FE) analysis was performed using the ABAQUS/Explicit solver. An ensemble-averaged transvalvular pressure waveform measured from in-vitro tests conducted in a pulse duplicator was applied to the leaflets. Through a parametric study, uniform TAV leaflet thickness was reduced from 0.5 to 0.18 mm. By reducing leaflet thickness, significantly higher stress values were found in the leaflet's fixed edge during systole, and in the commissures during diastole. Through dynamic FE simulations, the highest stress values were found during systole in the leaflet fixed edge. In contrast, at the peak of diastole high-stress regions were mainly observed in the commissures. The peak stress was increased by 178% and 507% within the leaflets after reducing the thickness of 0.5 mm to 0.18 mm at the peak of systole and diastole, respectively. The study results indicated that, the smaller the leaflet thickness, the higher the maximum principal stress. Increased mechanical stress on TAV leaflets may lead to accelerated tissue degeneration. By using a thinner leaflet, TAV durability may not atch with that of surgical bioprostheses.

The Drosophila HEM-2/NAP1 homolog KETTE controls axonal pathfinding and cytoskeletal organization.

PubMed

Hummel, T; Leifker, K; Klämbt, C

2000-04-01

In Drosophila, the correct formation of the segmental commissures depends on neuron-glial interactions at the midline. The VUM midline neurons extend axons along which glial cells migrate in between anterior and posterior commissures. Here, we show that the gene kette is required for the normal projection of the VUM axons and subsequently disrupts glial migration. Axonal projection defects are also found for many other moto- and interneurons. In addition, kette affects the cell morphology of mesodermal and epidermal derivatives, which show an abnormal actin cytoskeleton. The KETTE protein is homologous to the transmembrane protein HEM-2/NAP1 evolutionary conserved from worms to vertebrates. In vitro analysis has shown a specific interaction of the vertebrate HEM-2/NAP1 with the SH2-SH3 adapter protein NCK and the small GTPase RAC1, which both have been implicated in regulating cytoskeleton organization and axonal growth. Hypomorphic kette mutations lead to axonal defects similar to mutations in the Drosophila NCK homolog dreadlocks. Furthermore, we show that kette and dock mutants genetically interact. NCK is thought to interact with the small G proteins RAC1 and CDC42, which play a role in axonal growth. In line with these observations, a kette phenocopy can be obtained following directed expression of mutant DCDC42 or DRAC1 in the CNS midline. In addition, the kette mutant phenotype can be partially rescued by expression of an activated DRAC1 transgene. Our data suggest an important role of the HEM-2 protein in cytoskeletal organization during axonal pathfinding.

The Drosophila HEM-2/NAP1 homolog KETTE controls axonal pathfinding and cytoskeletal organization

PubMed Central

Hummel, Thomas; Leifker, Karin; Klämbt, Christian

2000-01-01

In Drosophila, the correct formation of the segmental commissures depends on neuron–glial interactions at the midline. The VUM midline neurons extend axons along which glial cells migrate in between anterior and posterior commissures. Here, we show that the gene kette is required for the normal projection of the VUM axons and subsequently disrupts glial migration. Axonal projection defects are also found for many other moto- and interneurons. In addition, kette affects the cell morphology of mesodermal and epidermal derivatives, which show an abnormal actin cytoskeleton. The KETTE protein is homologous to the transmembrane protein HEM-2/NAP1 evolutionary conserved from worms to vertebrates. In vitro analysis has shown a specific interaction of the vertebrate HEM-2/NAP1 with the SH2–SH3 adapter protein NCK and the small GTPase RAC1, which both have been implicated in regulating cytoskeleton organization and axonal growth. Hypomorphic kette mutations lead to axonal defects similar to mutations in the Drosophila NCK homolog dreadlocks. Furthermore, we show that kette and dock mutants genetically interact. NCK is thought to interact with the small G proteins RAC1 and CDC42, which play a role in axonal growth. In line with these observations, a kette phenocopy can be obtained following directed expression of mutant DCDC42 or DRAC1 in the CNS midline. In addition, the kette mutant phenotype can be partially rescued by expression of an activated DRAC1 transgene. Our data suggest an important role of the HEM-2 protein in cytoskeletal organization during axonal pathfinding. PMID:10766742

Recycling of the pulmonary valve: an elegant solution for secondary pulmonary regurgitation in patients with tetralogy of Fallot.

PubMed

Prêtre, René; Rosser, Barbara; Mueller, Christoph; Kretschmar, Oliver; Dave, Hitendu

2012-09-01

The purpose of this study was to review our experience with recycling of the pulmonary valve in cases of chronic pulmonary insufficiency after a transannular patch procedure as part of a repair of tetralogy of Fallot. Eight patients in whom the technique was used were reviewed. Technically, the valve was reapproximated at the anterior commissure if the valve leaflet was sufficiently developed and of good tissue quality. Additional corrections were performed in 5 patients (resection of an infundibular aneurysm [5 patients], repair of the tricuspid valve [1 patient]). The valve was competent with no or trivial regurgitation in 5 patients and a small regurgitation in 3 patients. There was no significant transvalvular gradient in 5 patients with tricuspid valves and a small gradient in 3 patients with a bicuspid valves (<23 mm Hg). The valve function remained stable over the follow-up period (median time, 32 months). Recycling of the pulmonary valve is an interesting concept that could avoid the necessary reoperations linked with valves or valved prostheses. The repair must be carefully followed in bicuspid valves because of a reduction in the opening area. Valve leaflets of good quality should be preserved during the primary repair of tetralogy of Fallot and the transannular incision should be made across the anterior commissure if possible. These steps should allow a few patients to profit from a recycling of their valves in the future. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Imaging the Effects of Oxygen Saturation Changes in Voluntary Apnea and Hyperventilation on Susceptibility-Weighted Imaging

PubMed Central

Chang, K.; Barnes, S.; Haacke, E.M.; Grossman, R.I.; Ge, Y.

2014-01-01

BACKGROUND AND PURPOSE Cerebrovascular oxygenation changes during respiratory challenges have clinically important implications for brain function, including cerebral autoregulation and the rate of brain metabolism. SWI is sensitive to venous oxygenation level by exploitation of the magnetic susceptibility of deoxygenated blood. We assessed cerebral venous blood oxygenation changes during simple voluntary breath-holding (apnea) and hyperventilation by use of SWI at 3T. MATERIALS AND METHODS We performed SWI scans (3T; acquisition time of 1 minute, 28 seconds; centered on the anterior commissure and the posterior commissure) on 10 healthy male volunteers during baseline breathing as well as during simple voluntary hyperventilation and apnea challenges. The hyperventilation and apnea tasks were separated by a 5-minute resting period. SWI venograms were generated, and the signal changes on SWI before and after the respiratory stress tasks were compared by means of a paired Student t test. RESULTS Changes in venous vasculature visibility caused by the respiratory challenges were directly visualized on the SWI venograms. The venogram segmentation results showed that voluntary apnea decreased the mean venous blood voxel number by 1.6% (P<.0001), and hyperventilation increased the mean venous blood voxel number by 2.7% (P<.0001). These results can be explained by blood CO2 changes secondary to the respiratory challenges, which can alter cerebrovascular tone and cerebral blood flow and ultimately affect venous oxygen levels. CONCLUSIONS These results highlight the sensitivity of SWI to simple and noninvasive respiratory challenges and its potential utility in assessing cerebral hemodynamics and vasomotor responses. PMID:24371029

Imaging the effects of oxygen saturation changes in voluntary apnea and hyperventilation on susceptibility-weighted imaging.

PubMed

Chang, K; Barnes, S; Haacke, E M; Grossman, R I; Ge, Y

2014-06-01

Cerebrovascular oxygenation changes during respiratory challenges have clinically important implications for brain function, including cerebral autoregulation and the rate of brain metabolism. SWI is sensitive to venous oxygenation level by exploitation of the magnetic susceptibility of deoxygenated blood. We assessed cerebral venous blood oxygenation changes during simple voluntary breath-holding (apnea) and hyperventilation by use of SWI at 3T. We performed SWI scans (3T; acquisition time of 1 minute, 28 seconds; centered on the anterior commissure and the posterior commissure) on 10 healthy male volunteers during baseline breathing as well as during simple voluntary hyperventilation and apnea challenges. The hyperventilation and apnea tasks were separated by a 5-minute resting period. SWI venograms were generated, and the signal changes on SWI before and after the respiratory stress tasks were compared by means of a paired Student t test. Changes in venous vasculature visibility caused by the respiratory challenges were directly visualized on the SWI venograms. The venogram segmentation results showed that voluntary apnea decreased the mean venous blood voxel number by 1.6% (P < .0001), and hyperventilation increased the mean venous blood voxel number by 2.7% (P < .0001). These results can be explained by blood CO2 changes secondary to the respiratory challenges, which can alter cerebrovascular tone and cerebral blood flow and ultimately affect venous oxygen levels. These results highlight the sensitivity of SWI to simple and noninvasive respiratory challenges and its potential utility in assessing cerebral hemodynamics and vasomotor responses. © 2014 by American Journal of Neuroradiology.

Regulation of GABAA and Glutamate Receptor Expression, Synaptic Facilitation and Long-Term Potentiation in the Hippocampus of Prion Mutant Mice

PubMed Central

Rangel, Alejandra; Madroñal, Noelia; Massó, Agnès Gruart i.; Gavín, Rosalina; Llorens, Franc; Sumoy, Lauro; Torres, Juan María; Delgado-García, José María; Río, José Antonio Del

2009-01-01

Background Prionopathies are characterized by spongiform brain degeneration, myoclonia, dementia, and periodic electroencephalographic (EEG) disturbances. The hallmark of prioniopathies is the presence of an abnormal conformational isoform (PrPsc) of the natural cellular prion protein (PrPc) encoded by the Prnp gene. Although several roles have been attributed to PrPc, its putative functions in neuronal excitability are unknown. Although early studies of the behavior of Prnp knockout mice described minor changes, later studies report altered behavior. To date, most functional PrPc studies on synaptic plasticity have been performed in vitro. To our knowledge, only one electrophysiological study has been performed in vivo in anesthetized mice, by Curtis and coworkers. They reported no significant differences in paired-pulse facilitation or LTP in the CA1 region after Schaffer collateral/commissural pathway stimulation. Methodology/Principal Findings Here we explore the role of PrPc expression in neurotransmission and neural excitability using wild-type, Prnp −/− and PrPc-overexpressing mice (Tg20 strain). By correlating histopathology with electrophysiology in living behaving mice, we demonstrate that both Prnp −/− mice but, more relevantly Tg20 mice show increased susceptibility to KA, leading to significant cell death in the hippocampus. This finding correlates with enhanced synaptic facilitation in paired-pulse experiments and hippocampal LTP in living behaving mutant mice. Gene expression profiling using Illumina™ microarrays and Ingenuity pathways analysis showed that 129 genes involved in canonical pathways such as Ubiquitination or Neurotransmission were co-regulated in Prnp −/− and Tg20 mice. Lastly, RT-qPCR of neurotransmission-related genes indicated that subunits of GABAA and AMPA-kainate receptors are co-regulated in both Prnp −/− and Tg20 mice. Conclusions/Significance Present results demonstrate that PrPc is necessary for the proper homeostatic functioning of hippocampal circuits, because of its relationships with GABAA and AMPA-Kainate neurotransmission. New PrPc functions have recently been described, which point to PrPc as a target for putative therapies in Alzheimer's disease. However, our results indicate that a “gain of function” strategy in Alzheimer's disease, or a “loss of function” in prionopathies, may impair PrPc function, with devastating effects. In conclusion, we believe that present data should be taken into account in the development of future therapies. PMID:19855845

White Matter Abnormalities in Autism and Unaffected Siblings.

PubMed

Jou, Roger J; Reed, Hannah E; Kaiser, Martha D; Voos, Avery C; Volkmar, Fred R; Pelphrey, Kevin A

2016-01-01

This study was conducted to identify a potential neuroendophenotype for autism using diffusion tensor imaging. Whole-brain, voxel-based analysis of fractional anisotropy was conducted in 50 children: 19 with autism, 20 unaffected siblings, and 11 controls. Relative to controls, participants with autism exhibited bilateral reductions in fractional anisotropy across association, commissure, and projection fibers. The most severely affected tracts included the uncinate fasciculus, forceps minor, and inferior fronto-occipital fasciculus. Unaffected siblings also exhibited reductions in fractional anisotropy, albeit less severe with fewer affected tracts, sparing the uncinate fasciculus and forceps minor. These results suggest the presence of a neuroendophenotype for autism.

Mechanical properties of the vocal fold. Stress-strain studies.

PubMed

Haji, T; Mori, K; Omori, K; Isshiki, N

1992-01-01

The viscoelasticity of the vocal and ventricular folds was experimentally assessed by analyzing the stress-strain relationships obtained using a newly developed measuring system. The degree of stiffness of the mid-membranous portion of the vocal fold was less than that near the anterior commissure or the vocal process. The ventricular fold was much less stiff and significantly more viscous than the vocal fold. At the membranous portion of the vocal fold, the degree of stiffness was less and that of viscosity greater at 2 mm above and below the free margin than at the free margin itself.

Oropharyngeal dysphagia and language delay in partial trisomy 9p: case report.

PubMed

Rossi, N F; Gatto, A R; Cola, P C; Souza, D H; Moretti-Ferreira, D; Giacheti, C M

2009-09-22

The phenotype of partial trisomy 9p includes global developmental delay, microcephaly, bulbous nose, downturned oral commissures, malformed ears, hypotonia, and severe cognitive and language disorders. We present a case report and a comparative review of clinical findings on this condition, focusing on speech-language development, cognitive abilities and swallowing evaluation. We suggest that oropharyngeal dysphagia should be further investigated, considering that pulmonary and nutritional disorders affect the survival and quality of life of the patient. As far as we know, this is the first study of a patient with partial trisomy 9p described with oropharyngeal dysphagia.

Environmental siting suitability analysis for commercial scale ocean renewable energy: A southeast Florida case study

NASA Astrophysics Data System (ADS)

Mulcan, Amanda

This thesis aims to facilitate the siting and implementation of Florida Atlantic University Southeast National Marine Renewable Energy Center (FAU SNMREC) ocean current energy (OCE) projects offshore southeastern Florida through the analysis of benthic anchoring conditions. Specifically, a suitability analysis considering all presently available biologic and geologic datasets within the legal framework of OCE policy and regulation was done. OCE related literature sources were consulted to assign suitability levels to each dataset, ArcGIS interpolations generated seafloor substrate maps, and existing submarine cable pathways were considered for OCE power cables. The finalized suitability map highlights the eastern study area as most suitable for OCE siting due to its abundance of sand/sediment substrate, existing underwater cable route access, and minimal biologic presence. Higher resolution datasets are necessary to locate specific OCE development locales, better understand their benthic conditions, and minimize potentially negative OCE environmental impacts.

Choice of Insulin in Type 2 Diabetes: A Southeast Asian Perspective

PubMed Central

Kalra, Sanjay; Thai, Hong Quang; Deerochanawong, Chaicharn; Su-Yen, Goh; Mohamed, Mafauzy; Latt, Tint Swe; Aye, Than Than; Latif, Zafar Ahmed; Katulanda, Prasad; Khun, Touch; Satha, Sum; Vongvandy, Vadsana

2017-01-01

Southeast Asia faces a diabetes epidemic, which has created significant challenges for health care. The unique Asian diabetes phenotype, coupled with peculiar lifestyle, diet, and healthcare-seeking behavior, makes it imperative to develop clinical pathways and guidelines which address local needs and requirements. From an insulin-centric viewpoint, the preparations prescribed in such pathways should be effective, safe, well tolerated, nonintrusive, and suitable for the use in multiple clinical situations including initiation and intensification. This brief communication describes the utility of premixed or dual action insulin in such clinical pathways and guidelines. PMID:28553609

Impact of Climate Change on Potential Distribution of Chinese Caterpillar Fungus (Ophiocordyceps sinensis) in Nepal Himalaya

PubMed Central

Shrestha, Uttam Babu; Bawa, Kamaljit S.

2014-01-01

Climate change has already impacted ecosystems and species and substantial impacts of climate change in the future are expected. Species distribution modeling is widely used to map the current potential distribution of species as well as to model the impact of future climate change on distribution of species. Mapping current distribution is useful for conservation planning and understanding the change in distribution impacted by climate change is important for mitigation of future biodiversity losses. However, the current distribution of Chinese caterpillar fungus, a flagship species of the Himalaya with very high economic value, is unknown. Nor do we know the potential changes in suitable habitat of Chinese caterpillar fungus caused by future climate change. We used MaxEnt modeling to predict current distribution and changes in the future distributions of Chinese caterpillar fungus in three future climate change trajectories based on representative concentration pathways (RCPs: RCP 2.6, RCP 4.5, and RCP 6.0) in three different time periods (2030, 2050, and 2070) using species occurrence points, bioclimatic variables, and altitude. About 6.02% (8,989 km2) area of the Nepal Himalaya is suitable for Chinese caterpillar fungus habitat. Our model showed that across all future climate change trajectories over three different time periods, the area of predicted suitable habitat of Chinese caterpillar fungus would expand, with 0.11–4.87% expansion over current suitable habitat. Depending upon the representative concentration pathways, we observed both increase and decrease in average elevation of the suitable habitat range of the species. PMID:25180515

Impact of climate change on potential distribution of Chinese caterpillar fungus (Ophiocordyceps sinensis) in Nepal Himalaya.

PubMed

Shrestha, Uttam Babu; Bawa, Kamaljit S

2014-01-01

Climate change has already impacted ecosystems and species and substantial impacts of climate change in the future are expected. Species distribution modeling is widely used to map the current potential distribution of species as well as to model the impact of future climate change on distribution of species. Mapping current distribution is useful for conservation planning and understanding the change in distribution impacted by climate change is important for mitigation of future biodiversity losses. However, the current distribution of Chinese caterpillar fungus, a flagship species of the Himalaya with very high economic value, is unknown. Nor do we know the potential changes in suitable habitat of Chinese caterpillar fungus caused by future climate change. We used MaxEnt modeling to predict current distribution and changes in the future distributions of Chinese caterpillar fungus in three future climate change trajectories based on representative concentration pathways (RCPs: RCP 2.6, RCP 4.5, and RCP 6.0) in three different time periods (2030, 2050, and 2070) using species occurrence points, bioclimatic variables, and altitude. About 6.02% (8,989 km2) area of the Nepal Himalaya is suitable for Chinese caterpillar fungus habitat. Our model showed that across all future climate change trajectories over three different time periods, the area of predicted suitable habitat of Chinese caterpillar fungus would expand, with 0.11-4.87% expansion over current suitable habitat. Depending upon the representative concentration pathways, we observed both increase and decrease in average elevation of the suitable habitat range of the species.

Development of the septal region in the rat. II. Morphogenesis in normal and x-irradiated embryos

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bayer, S.A.

1979-01-01

Morphogenesis of the septal region was examined in normal rat embryos from embryonic day (E) 10 to E22. The greater part of the septal region is postulated to form from two separate anlagen which can be clearly distinguished in the telencephalon by E13 and E14. One lies in the anterior ventromedial wall and presumably forms the nucleus of the diagonal band, medial, lateral, and triangular septal nuclei. The other lies in the posterior ventrolateral ridge and presumably forms the bed nuclei of the stria terminalis and the anterior commissure. On E15, the early differentiating cells in these anlagen fuse inmore » the same region where the anterior commissure will cross on E17. On E16 and E17, a prominent subependymal zone develops in the anterior septal region and presumably gives rise to the nucleus accumbens. A quantitative analysis was made of three cell zones (neuroepithelium, subependymal zone, differentiating cell zone) at coronal levels through the developing nucleus accumbens and the nucleus of the diagonal band (anterior level) and the medial and lateral septal nuclei (middle and posterior levels). To accurately locate regions of primitive mitotic and migratory cells within the zones at each level, the number of cells surviving a single exposure to 200 R x-rays in embryonic brains (E15 to E22) were compared with controls. Each zone responded differently to x-ray insult. The radiosensitivity of the neuroepithelium decreases significantly after E19; the subependymal zone is highly radiosensitive throughout; the differentiating cell zone is radioresistant throughout. The significance of these findings is discussed in the light of the autoradiographic determination of the time of formation of septal neurons.« less

Distribution of 3H-GABA uptake sites in the nematode Ascaris

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guastella, J.; Stretton, A.O.

1991-05-22

The distribution of uptake sites for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the nematode Ascaris suum was examined by autoradiography of 3H-GABA uptake. Single neural processes in both the ventral and dorsal nerve cords were labeled with 3H-GABA. Serial section analysis identified the cells of origin of these processes as the RMEV-like and RMED-like neurons. These cells belong to a set of four neurons in the nerve ring, all of which are labeled by 3H-GABA. 3H-GABA labeling of at least two other sets of cephalic neurons was seen. One of these pairs consists of medium-sized lateral ganglia neurons, locatedmore » at the level of the amphid commissure bundle. A second pair is located in the lateral ganglia at the level of the deirid commissure bundle. The position and size of these lateral ganglia cells suggest that they are the GABA-immunoreactive lateral ganglia cells frequently seen in whole-mount immunocytochemical preparations. Four neuronal cell bodies located in the retrovesicular ganglion were also labeled with 3H-GABA. These cells, which are probably cholinergic excitatory motor neurons, do not contain detectable GABA-like immunoreactivity. Heavy labeling of muscle cells was also observed. The ventral and dorsal nerve cord inhibitory motor neurons, which are known to contain GABA-like immunoreactivity, were not labeled above background with 3H-GABA. Together with the experiments reported previously, these results define three classes of GABA-associated neurons in Ascaris: (1) neurons that contain endogenous GABA and possess a GABA uptake system; (2) neurons that contain endogenous GABA, but that either lack a GABA uptake system or possess a GABA uptake system of low activity; (3) neurons that possess a GABA uptake system, but that lack endogenous GABA.« less

Organization of the sleep-related neural systems in the brain of the minke whale (Balaenoptera acutorostrata).

PubMed

Dell, Leigh-Anne; Karlsson, Karl Ae; Patzke, Nina; Spocter, Muhammad A; Siegel, Jerome M; Manger, Paul R

2016-07-01

The current study analyzed the nuclear organization of the neural systems related to the control and regulation of sleep and wake in the basal forebrain, diencephalon, midbrain, and pons of the minke whale, a mysticete cetacean. While odontocete cetaceans sleep in an unusual manner, with unihemispheric slow wave sleep (USWS) and suppressed REM sleep, it is unclear whether the mysticete whales show a similar sleep pattern. Previously, we detailed a range of features in the odontocete brain that appear to be related to odontocete-type sleep, and here present our analysis of these features in the minke whale brain. All neural elements involved in sleep regulation and control found in bihemispheric sleeping mammals and the harbor porpoise were present in the minke whale, with no specific nuclei being absent, and no novel nuclei being present. This qualitative similarity relates to the cholinergic, noradrenergic, serotonergic and orexinergic systems, and the GABAergic elements of these nuclei. Quantitative analysis revealed that the numbers of pontine cholinergic (274,242) and noradrenergic (203,686) neurons, and hypothalamic orexinergic neurons (277,604), are markedly higher than other large-brained bihemispheric sleeping mammals. Small telencephalic commissures (anterior, corpus callosum, and hippocampal), an enlarged posterior commissure, supernumerary pontine cholinergic and noradrenergic cells, and an enlarged peripheral division of the dorsal raphe nuclear complex of the minke whale, all indicate that the suite of neural characteristics thought to be involved in the control of USWS and the suppression of REM in the odontocete cetaceans are present in the minke whale. J. Comp. Neurol. 524:2018-2035, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Saddle-shaped mitral valve annuloplasty rings experience lower forces compared with flat rings.

PubMed

Jensen, Morten O; Jensen, Henrik; Smerup, Morten; Levine, Robert A; Yoganathan, Ajit P; Nygaard, Hans; Hasenkam, J Michael; Nielsen, Sten L

2008-09-30

New insight into the 3D dynamic behavior of the mitral valve has prompted a reevaluation of annuloplasty ring designs. Force balance analysis indicates correlation between annulus forces and stresses in leaflets and chords. Improving this stress distribution can intuitively enhance the durability of mitral valve repair. We tested the hypothesis that saddle-shaped annuloplasty rings have superior uniform systolic force distribution compared with a nonuniform force distribution in flat annuloplasty rings. Sixteen 80-kg pigs had a flat (n=8) or saddle-shaped (n=8) mitral annuloplasty ring implanted. Mitral annulus 3D dynamic geometry was obtained with sonomicrometry before ring insertion. Strain gauges mounted on dedicated D-shaped rigid flat and saddle-shaped annuloplasty rings provided the intraoperative force distribution perpendicular to the annular plane. Average systolic annular height to commissural width ratio before ring implantation was 14.0%+/-1.6%. After flat and saddle shaped ring implantation, the annulus was fixed in the diastolic (9.0%+/-1.0%) and systolic (14.3%+/-1.3%) configuration, respectively (P<0.01). Force accumulation was seen from the anterior (0.72N+/-0.14N) and commissural annular segments (average 1.38N+/-0.27N) of the flat rings. In these segments, the difference between the 2 types of rings was statistically significant (P<0.05). The saddle-shaped annuloplasty rings did not experience forces statistically significantly larger than zero in any annular segments. Saddle-shaped annuloplasty rings provide superior uniform annular force distribution compared to flat rings and appear to represent a configuration that minimizes out-of-plane forces that could potentially be transmitted to leaflets and chords. This may have important implications for annuloplasty ring selections.

Impact of different aortic valve calcification patterns on the outcome of transcatheter aortic valve implantation: A finite element study.

PubMed

Sturla, Francesco; Ronzoni, Mattia; Vitali, Mattia; Dimasi, Annalisa; Vismara, Riccardo; Preston-Maher, Georgia; Burriesci, Gaetano; Votta, Emiliano; Redaelli, Alberto

2016-08-16

Transcatheter aortic valve implantation (TAVI) can treat symptomatic patients with calcific aortic stenosis. However, the severity and distribution of the calcification of valve leaflets can impair the TAVI efficacy. Here we tackle this issue from a biomechanical standpoint, by finite element simulation of a widely adopted balloon-expandable TAVI in three models representing the aortic root with different scenarios of calcific aortic stenosis. We developed a modeling approach realistically accounting for aortic root pressurization and complex anatomy, detailed calcification patterns, and for the actual stent deployment through balloon-expansion. Numerical results highlighted the dependency on the specific calcification pattern of the "dog-boning" of the stent. Also, local stent distortions were associated with leaflet calcifications, and led to localized gaps between the TAVI stent and the aortic tissues, with potential implications in terms of paravalvular leakage. High stresses were found on calcium deposits, which may be a risk factor for stroke; their magnitude and the extent of the affected regions substantially increased for the case of an "arc-shaped" calcification, running from commissure to commissure. Moreover, high stresses due to the interaction between the aortic wall and the leaflet calcifications were computed in the annular region, suggesting an increased risk for annular damage. Our analyses suggest a relation between the alteration of the stresses in the native anatomical components and prosthetic implant with the presence and distribution of relevant calcifications. This alteration is dependent on the patient-specific features of the calcific aortic stenosis and may be a relevant indicator of suboptimal TAVI results. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Thyroid gland invasion in advanced squamous cell carcinoma of the larynx and hypopharynx.

PubMed

Mangussi-Gomes, João; Danelon-Leonhardt, Fernando; Moussalem, Guilherme Figner; Ahumada, Nicolas Galat; Oliveira, Cleydson Lucena; Hojaij, Flávio Carneiro

Squamous cell carcinoma of the larynx and hypopharynx has the potential to invade the thyroid gland. Despite this risk, the proposition of either partial or total thyroidectomy as part of the surgical treatment of all such cases remains controversial. To evaluate the frequency of invasion of the thyroid gland in patients with advanced laryngeal or hypopharyngeal squamous cell carcinoma submitted to total laryngectomy or pharyngolaryngectomy and thyroidectomy; to determine whether clinic-pathological characteristics can predict glandular involvement. A retrospective case series with chart review, from January 1998 to July 2013, was undertaken in a tertiary care university medical center. An inception cohort of 83 patients with larynx/hypopharynx squamous cell carcinoma was considered. All patients had advanced stage disease (clinically T3-T4) and underwent total laryngectomy or total pharyngolaryngectomy in association with thyroidectomy. Adjuvant therapy was indicated when tumor or neck conditions required. Frequency of thyroid cartilage invasion was calculated; univariate and multivariate analysis of demographic, clinical and pathological characteristics associated with cartilage invasion were performed. The overall frequency of invasion of the thyroid gland was 18.1%. Glandular involvement was associated with invasion of the following structures: anterior commissure (odds ratio=5.13; 95% confidence interval 1.07-24.5), subglottis (odds ratio=12.44; 95% confidence interval 1.55-100.00) and cricoid cartilage (odds ratio=15.95; 95% confidence interval 4.23-60.11). Invasion of the thyroid gland is uncommon in the context of laryngopharyngeal squamous cell carcinoma. Clinical and pathological features such as invasion of the anterior commissure, subglottis and cricoid cartilage are more associated with glandular invasion. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Geometric differences of the mitral apparatus between ischemic and dilated cardiomyopathy with significant mitral regurgitation: real-time three-dimensional echocardiography study

NASA Technical Reports Server (NTRS)

Kwan, Jun; Shiota, Takahiro; Agler, Deborah A.; Popovic, Zoran B.; Qin, Jian Xin; Gillinov, Marc A.; Stewart, William J.; Cosgrove, Delos M.; McCarthy, Patrick M.; Thomas, James D.

2003-01-01

BACKGROUND: This study was conducted to elucidate the geometric differences of the mitral apparatus in patients with significant mitral regurgitation caused by ischemic cardiomyopathy (ICM-MR) and by idiopathic dilated cardiomyopathy (DCM-MR) by use of real-time 3D echocardiography (RT3DE). METHODS AND RESULTS: Twenty-six patients with ICM-MR caused by posterior infarction, 18 patients with DCM-MR, and 8 control subjects were studied. With the 3D software, commissure-commissure plane and 3 perpendicular anteroposterior (AP) planes were generated for imaging the medial, central, and lateral sides of the mitral valve (MV) during mid systole. In 3 AP planes, the angles between the annular plane and each leaflet (anterior, Aalpha; posterior, Palpha) were measured. In ICM-MR, Aalpha measured in the medial and central planes was significantly larger than that in the lateral plane (39+/-5 degrees, 34+/-6 degrees, and 27+/-5 degrees, respectively; P<0.01), whereas Palpha showed no significant difference in any of the 3 AP planes (61+/-7 degrees, 57+/-7 degrees, and 56+/-7 degrees, P>0.05). In DCM-MR, both Aalpha (38+/-8 degrees, 37+/-9 degrees, and 36+/-7 degrees, P>0.05) and Palpha (59+/-6 degrees, 58+/-5 degrees, and 57+/-6 degrees, P>0.05) revealed no significant differences in the 3 planes. CONCLUSIONS: The pattern of MV deformation from the medial to the lateral side was asymmetrical in ICM-MR, whereas it was symmetrical in DCM-MR. RT3DE is a helpful tool for differentiating the geometry of the mitral apparatus between these 2 different types of functional mitral regurgitation.

Change of signs, symptoms and voice quality evaluations throughout a 3- to 6-month empirical treatment for laryngopharyngeal reflux disease.

PubMed

Lechien, J R; Finck, C; Khalife, M; Huet, K; Delvaux, V; Picalugga, M; Harmegnies, B; Saussez, S

2018-05-16

To assess the usefulness of voice quality measurements as a treatment outcome in patients with laryngopharyngeal reflux (LPR)-related symptoms. Prospective uncontrolled multi-centre study. A total of 80 clinically diagnosed LPR patients with a reflux finding score (RFS)>7 and a reflux symptom index (RSI)>13 were treated with pantoprazole and diet recommendations during 3 or 6 months, according to their evolution. RSI; RFS; blinded Grade, Roughness, Breathiness, Asthenia, Strain and Instability (GRBASI) and aerodynamic and acoustic measurements were evaluated at baseline, 3 months (n = 80), and 6 months (n = 41) post-treatment. We conducted a correlation analysis between the adherence to the diet, and the evolution of both signs and symptoms and between videolaryngostroboscopic signs and acoustic measurements. Reflux symptom index, RFS, perceptual voice quality evaluations (dysphonia, roughness, strain and instability), and aerodynamic and acoustic measurements (ie, percent jitter and percent shimmer) were significantly improved at 3 months post-treatment but not at 6 months. Percent jitter was the most useful outcome for evaluating the clinical evolution of patients throughout the treatment course. A significant relationship between globus sensation and posterior commissure hypertrophy was documented; both seemed to significantly improve from 3 to 6 months. The correlation analysis revealed correlations between adherence to diet recommendations and the improvement of symptoms and between posterior commissure granulation severity and acoustic measurement impairments. Voice quality improved in a manner similar to both signs and symptoms throughout a 6-month empirical treatment with better improvement the 3 first months. Voice quality assessments can be used as indicators of treatment effectiveness in patients with LPR-related symptoms. © 2018 John Wiley & Sons Ltd.

Total ellipse of the heart valve: the impact of eccentric stent distortion on the regional dynamic deformation of pericardial tissue leaflets of a transcatheter aortic valve replacement

PubMed Central

Gunning, Paul S.; Saikrishnan, Neelakantan; Yoganathan, Ajit P.; McNamara, Laoise M.

2015-01-01

Transcatheter aortic valve replacements (TAVRs) are a percutaneous alternative to surgical aortic valve replacements and are used to treat patients with aortic valve stenosis. This minimally invasive procedure relies on expansion of the TAVR stent to radially displace calcified aortic valve leaflets against the aortic root wall. However, these calcium deposits can impede the expansion of the device causing distortion of the valve stent and pericardial tissue leaflets. The objective of this study was to elucidate the impact of eccentric TAVR stent distortion on the dynamic deformation of the tissue leaflets of the prosthesis in vitro. Dual-camera stereophotogrammetry was used to measure the regional variation in strain in a leaflet of a TAVR deployed in nominal circular and eccentric (eccentricity index = 28%) orifices, representative of deployed TAVRs in vivo. It was observed that (i) eccentric stent distortion caused incorrect coaptation of the leaflets at peak diastole resulting in a ‘peel-back’ leaflet geometry that was not present in the circular valve and (ii) adverse bending of the leaflet, arising in the eccentric valve at peak diastole, caused significantly higher commissure strains compared with the circular valve in both normotensive and hypertensive pressure conditions (normotension: eccentric = 13.76 ± 2.04% versus circular = 11.77 ± 1.61%, p = 0.0014, hypertension: eccentric = 15.07 ± 1.13% versus circular = 13.56 ± 0.87%, p = 0.0042). This study reveals that eccentric distortion of a TAVR stent can have a considerable impact on dynamic leaflet deformation, inducing deleterious bending of the leaflet and increasing commissures strains, which might expedite leaflet structural failure compared to leaflets in a circular deployed valve. PMID:26674192

Modified Lengthening Temporalis Myoplasty Involving an Extended Lazy-S Incision to Avoid Facial Scar Formation.

PubMed

Oji, Tomito; Hayashi, Akiteru; Ogino, Akihiro; Onishi, Kiyoshi

2018-05-01

Lengthening temporalis myoplasty is a faster and less invasive alternative to free muscle transfer for smile reconstruction. However, it requires a nasolabial fold incision, which leaves a midfacial scar. Based on esthetic considerations, a modified approach, involving an extended lazy-S (parotidectomy) incision instead of a nasolabial fold incision, was developed. A cadaveric study involving 10 hemifaces was conducted. From February 2013 to March 2016, the modified lengthening temporalis myoplasty procedure was employed in 10 patients. The results were graded from 1 (poor) to 5 (excellent) according to the Terzis grading system. The excursion of the oral commissure was also measured. The extended lazy-S incision provides easy and safe access to the coronoid process and good visibility. The patients' mean age was 56.5 years, and the mean duration of the postoperative follow-up period was 22.2 months. The patients' underlying conditions included acoustic neuroma (n = 2), Bell palsy (n = 3), congenital conditions (n = 2), brain infarction (n = 1), Ramsay Hunt syndrome (n = 1), and malignant parotid lymphoma (n = 1). One patient suffered a surgical site infection, which was successfully treated with irrigation. All the patients achieved improvements in smile symmetry: 2, 5, and 3 patients obtained excellent, good, and moderate results, respectively. The excursion of the oral commissure ranged from 5 to 10 mm. The modified lengthening temporalis myoplasty procedure provides satisfactory functional outcomes without causing significant complications. It does not leave a facial scar and is a preferable option, especially for young and female patients, and patients who have undergone ablative surgery involving the parotid region.

Tricuspid annuloplasty with the MC3 ring and septal plication technique.

PubMed

Isomura, Tadashi; Hirota, Masanori; Hoshino, Joji; Fukada, Yasuhisa; Kondo, Taichi; Takahashi, Yu

2015-01-01

Functional tricuspid regurgitation is caused by annular dilation mainly in the posterior annulus. However, ring annuloplasty does not always prevent the recurrence of tricuspid regurgitation due to dilation of the septal annulus. We developed a septal plication technique with a 3-dimensional MC3 ring. Between 2006 and 2011, 76 patients (male/female 30/46; mean age 68 ± 11 years) with functional tricuspid regurgitation received tricuspid ring annuloplasty. After placement of the annular sutures, the 3 commissural ring portions were fixed on the equivalent commissures to plicate the anterior and posterior annulus. The end of the septal ring portion was fixed at the optimal annular position to obtain minimal tricuspid regurgitation. All patients were followed-up for a mean of 47 ± 18 months; the longest duration was 79 months. Although there was no operative death, one patient died of sepsis during hospitalization (hospital mortality 1.3%). After implantation of the MC3 ring (mean size 31.0 ± 3.3 mm), additional edge-to-edge sutures were required for minor leakage in 5 (7%) patients. The degree of tricuspid regurgitation was significantly reduced at discharge (0.5 ± 0.6) and midterm (0.6 ± 0.6) compared to 2.5 ± 0.7 before the operation (p < 0.0001). The surgical durability of the MC3 ring was satisfactory at early and midterm follow-up, suggesting that correct plication of the septal annulus is effective for tricuspid ring annuloplasty with a 3-dimensional MC3 ring. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Oral candidal species among smokers and non-smokers.

PubMed

Rasool, S; Siar, C H; Ng, K P

2005-11-01

To determine the various oral Candidal species among healthy Malaysian adults. Case-control study. This study was collaborated between the Department of Medical Microbiology, Faculty of Medicine and Department of Oral Pathology, Oral Medicine and Periodontology, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia, between September 2002 till January 2004. One hundred adults (50 smokers and 50 non-smokers), aged between 40 and 70 years were studied. Swabs and carbohydrate assimilation (Saboraud Dextrose Agar, Corn Meal Agar, API 20C AUX System) were performed. Specimens were collected from dorsum of the tongue, buccal mucosa and commissures (right and left each). Colony forms were established by positive colony forming units, on SDA medium (24-48 hours). Germ tube test for (true/pseudohyphae) growth was done on Corn Meal Agar Medium. Candida biotypes were evaluated by API 20C AUX system, which had a numerical 7 digit profile, added to evaluate a definite Candida species. Thirty-five percent of Malaysian adults harbored Candida intraorally. Candidal species identified among 100 subjects had C. albicans (27) 77%, C. glabrata (3) 8%, C. famata, C. tropicalis, C. krusei, C. lusitaniae and C. guilliermondii (1) 3% each. Thirty-three positive cases comprised of 35 species i.e. two cases had two species each. Fifty seven percent of these were smokers and 43% non-smokers. These included 40% Chinese, 36% Malays and 24% Indians. Species were, however, not specified according to intra-oral sites i.e. buccal, commissural mucosa and dorsum of tongue. On this series C. albicans is the most common species found in the oral cavity of Malaysian adults. It is equally frequent in smokers and non-smokers, but showed a predilection for the ethnic Chinese group.

Disorder-Specific Alteration in White Matter Structural Property in Adults With Autism Spectrum Disorder Relative to Adults With ADHD and Adult Controls.

PubMed

Chiang, Huey-Ling; Chen, Yu-Jen; Lin, Hsiang-Yuan; Tseng, Wen-Yih Isaac; Gau, Susan Shur-Fen

2017-01-01

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are not only often comorbid but also overlapped in behavioral and cognitive abnormalities. Little is known about whether these shared phenotypes are based on common or different underlying neuropathologies. Therefore, this study aims to examine the disorder-specific alterations in white matter (WM) structural property. The three comparison groups included 23 male adults with ASD (21.4 ± 3.1 years), 32 male adults with ADHD (23.4 ± 3.3 years), and 29 age-matched healthy male controls (22.4 ± 3.3 years). After acquisition of the diffusion spectrum imaging (DSI), whole brain tractography was reconstructed by a tract-based automatic analysis. Generalized fractional anisotropy (GFA) values were computed to indicate tract-specific WM property with adjusted P value < 0.05 for false discovery rate correction. Post hoc analyses revealed that men with ASD exhibited significant lower GFA values than men with ADHD and male controls in six identified fiber tracts: the right arcuate fasciculus, right cingulum (hippocampal part), anterior commissure, and three callosal fibers (ventrolateral prefrontal cortex part, precentral part, superior temporal part). There was no significant difference in the GFA values of any of the fiber tracts between men with ADHD and controls. In men with ASD, the GFA values of the right arcuate fasciculus and right cingulum (hippocampal part) were negatively associated with autistic social-deficit symptoms, and the anterior commissure GFA value was positively correlated with intelligence. This study highlights the disorder-specific alteration of the microstructural property of WM tracts in male adults with ASD. Hum Brain Mapp 38:384-395, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Three-dimensional Reconstruction of Scar Contracture-bearing Axilla and Digital Webs Using the Square Flap Method.

PubMed

Huang, Chenyu; Ogawa, Rei

2014-05-01

Joint scar contractures are characterized by tight bands of soft tissue that bridge the 2 ends of the joint like a web. Classical treatment methods such as Z-plasties are mainly based on 2-dimensional designs. Our square flap method is an alternative surgical method that restores the span of the web in a stereometric fashion, thereby reconstructing joint function. In total, 20 Japanese patients with joint scar contractures on the axillary (n = 10) or first digital web (n = 10) underwent square flap surgery. The maximum range of motion and commissure length were measured before and after surgery. A theoretical stereometric geometrical model of the square flap was established to compare it to the classical single (60 degree), 4-flap (45 degree), and 5-flap (60 degree) Z-plasties in terms of theoretical web reconstruction efficacy. All cases achieved 100% contracture release. The maximum range of motion and web space improved after square flap surgery (P = 0.001). Stereometric geometrical modeling revealed that the standard square flap (α = 45 degree; β = 90 degree) yields a larger flap area, length/width ratio, and postsurgical commissure length than the Z-plasties. It can also be adapted by varying angles α and β, although certain angle thresholds must be met to obtain the stereometric advantages of this method. When used to treat joint scar contractures, the square flap method can fully span the web space in a stereometric manner, thus yielding a close-to-original shape and function. Compared with the classical Z-plasties, it also provides sufficient anatomical blood supply while imposing the least physiological tension on the adjacent skin.

Three-dimensional Reconstruction of Scar Contracture-bearing Axilla and Digital Webs Using the Square Flap Method

PubMed Central

Huang, Chenyu

2014-01-01

Background: Joint scar contractures are characterized by tight bands of soft tissue that bridge the 2 ends of the joint like a web. Classical treatment methods such as Z-plasties are mainly based on 2-dimensional designs. Our square flap method is an alternative surgical method that restores the span of the web in a stereometric fashion, thereby reconstructing joint function. Methods: In total, 20 Japanese patients with joint scar contractures on the axillary (n = 10) or first digital web (n = 10) underwent square flap surgery. The maximum range of motion and commissure length were measured before and after surgery. A theoretical stereometric geometrical model of the square flap was established to compare it to the classical single (60 degree), 4-flap (45 degree), and 5-flap (60 degree) Z-plasties in terms of theoretical web reconstruction efficacy. Results: All cases achieved 100% contracture release. The maximum range of motion and web space improved after square flap surgery (P = 0.001). Stereometric geometrical modeling revealed that the standard square flap (α = 45 degree; β = 90 degree) yields a larger flap area, length/width ratio, and postsurgical commissure length than the Z-plasties. It can also be adapted by varying angles α and β, although certain angle thresholds must be met to obtain the stereometric advantages of this method. Conclusions: When used to treat joint scar contractures, the square flap method can fully span the web space in a stereometric manner, thus yielding a close-to-original shape and function. Compared with the classical Z-plasties, it also provides sufficient anatomical blood supply while imposing the least physiological tension on the adjacent skin. PMID:25289342

Commissural NTS lesions enhance the pressor response to central cholinergic and adrenergic activation.

PubMed

Vieira, Alexandre A; De Luca, Laurival A; Colombari, Eduardo; Colombari, Debora S A; Menani, José V

2012-07-11

Electrolytic lesions of the commissural nucleus of the solitary tract (commNTS) in rats enhance the pressor response to bilateral carotid occlusion or to intravenous infusion of hypertonic NaCl without changing baroreflex responses. In an opposite direction, commNTS lesions abolish the pressor responses to peripheral chemoreflex activation. These opposite effects of commNTS lesions apparently result from an impairment of sympathetic activation in one case and in a facilitation of vasopressin secretion in the others. In the present study, we investigated the effects of the electrolytic lesions of the commNTS in the pressor responses that depend on sympathetic activation and vasopressin secretion produced by central cholinergic or adrenergic activation with intracerebroventricular (i.c.v.) injections of carbachol or noradrenaline, respectively, in unanesthetized rats. Male Holtzman rats (280-320 g, n=8-15/group) with acute (1 day) or chronic (21 days) sham or commNTS lesions (1 mA×10 s) and a stainless steel cannula implanted in the lateral ventricle were used. Acute commNTS lesions increased the pressor response to i.c.v. injection of carbachol (0.5 nmol/1μ1) (52 ± 2, vs. sham: 37 ± 2mm Hg) or noradrenaline (80 nmol/1μl) (45 ± 6, vs. sham: 30 ± 3 mm Hg), whereas chronic commNTS lesions did not affect the pressor responses to the same treatments. Lesions of the commNTS impaired chemoreflex responses produced by intravenous KCN, without changing baroreflex responses. The results suggest that commNTS-dependent inhibitory signals are involved in the modulation of the pressor responses to central cholinergic and adrenergic activation, probably limiting vasopressin secretion. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Repair of anomalous aortic origin of a coronary artery in 113 patients: a Congenital Heart Surgeons' Society report.

PubMed

Poynter, Jeffrey A; Bondarenko, Igor; Austin, Erle H; DeCampli, William M; Jacobs, Jeffrey P; Ziemer, Gerhard; Kirshbom, Paul M; Tchervenkov, Christo I; Karamlou, Tara; Blackstone, Eugene H; Walters, Henry L; Gaynor, J William; Mery, Carlos M; Pearl, Jeffrey M; Brothers, Julie A; Caldarone, Christopher A; Williams, William G; Jacobs, Marshall L; Mavroudis, Constantine

2014-10-01

Anomalous aortic origin of a coronary artery (AAOCA) encompasses a wide morphologic spectrum, which has impeded consensus regarding indications for the diverse repair strategies. We constructed a profile of current surgical techniques and explore their application to morphologic variants. Patients<30 years old (n=113) with isolated AAOCA who underwent operations at 29 Congenital Heart Surgeons Society (CHSS) institutions from 1998 to 2012 were identified from the CHSS AAOCA Registry. Operative findings were related to surgical techniques at index repairs by cross-tabulation. Anomalous origin of the left main or left anterior descending coronary artery was present in 33 (29%) patients and of the right coronary artery in 78 (69%) patients; 2 arteries originated directly above the commissure between the left and right sinuses. There were 101 (89%) interarterial and intramural (IA/IM) arteries, 10 (9%) were interarterial but not intramural (IA/NIM) and 2 (2%) were neither interarterial nor intramural. Intramural arteries were unroofed in 100 (88%) operations, usually with intimal tacking after incision (n=47) or excision (n=25) of the common wall. Coronary reimplantation (n=11), pulmonary artery relocation (n=7; 5 for IA/NIM), simple ostioplasty (without unroofing; n=3), coronary artery bypass grafting (n=2), and ostial window (n=1) were less common. In 37 (33%) operations, a valvar commissure was taken down; 33 were resuspended. Current surgical repair of AAOCA is individualized to morphology, particularly the presence of intramural and/or interarterial segments. This report is foundational for future planned CHSS studies that will examine interventional and noninterventional outcomes and ultimately guide management of AAOCA. © The Author(s) 2014.

Using "Functional" Target Coordinates of the Subthalamic Nucleus to Assess the Indirect and Direct Methods of the Preoperative Planning: Do the Anatomical and Functional Targets Coincide?

PubMed

Rabie, Ahmed; Verhagen Metman, Leo; Slavin, Konstantin V

2016-12-21

To answer the question of whether the anatomical center of the subthalamic nucleus (STN), as calculated indirectly from stereotactic atlases or by direct visualization on magnetic resonance imaging (MRI), corresponds to the best functional target. Since the neighboring red nucleus (RN) is well visualized on MRI, we studied the relationships of the final target to its different borders. We analyzed the data of 23 PD patients (46 targets) who underwent bilateral frame-based STN deep brain stimulation (DBS) procedure with microelectrode recording guidance. We calculated coordinates of the active contact on DBS electrode on postoperative MRI, which we referred to as the final "functional/optimal" target. The coordinates calculated by the atlas-based "indirect" and "direct" methods, as well as the coordinates of the different RN borders were compared to these final coordinates. The mean ± SD of the final target coordinates was 11.7 ± 1.5 mm lateral (X), 2.4 ± 1.5 mm posterior (Y), and 6.1 ± 1.7 mm inferior to the mid-commissural point (Z). No significant differences were found between the "indirect" X, Z coordinates and those of the final targets. The "indirect" Y coordinate was significantly posterior to Y of the final target, with mean difference of 0.6 mm ( p = 0.014). No significant differences were found between the "direct" X, Y, and Z coordinates and those of the final targets. The functional STN target is located in direct proximity to its anatomical center. During preoperative targeting, we recommend using the "direct" method, and taking into consideration the relationships of the final target to the mid-commissural point (MCP) and the different RN borders.

Modelling and Decision Support of Clinical Pathways

NASA Astrophysics Data System (ADS)

Gabriel, Roland; Lux, Thomas

The German health care market is under a rapid rate of change, forcing especially hospitals to provide high-quality services at low costs. Appropriate measures for more effective and efficient service provision are process orientation and decision support by information technology of clinical pathway of a patient. The essential requirements are adequate modelling of clinical pathways as well as usage of adequate systems, which are capable of assisting the complete path of a patient within a hospital, and preferably also outside of it, in a digital way. To fulfil these specifications the authors present a suitable concept, which meets the challenges of well-structured clinical pathways as well as rather poorly structured diagnostic and therapeutic decisions, by interplay of process-oriented and knowledge-based hospital information systems.

Microbial degradation and toxicity of hexahydro-1,3,5-trinitro-1,3,5-triazine.

PubMed

Khan, Muhammad Imran; Lee, Jaejin; Park, Joonhong

2012-10-01

In the present work, current knowledge on the potential fate, microbial degradation, and toxicity of hexahydro- 1,3,5-trinitro-1,3,5-triazine (RDX) was thoroughly reviewed, focusing on the toxicological assessment of a variety of potential RDX degradation pathways in bacteria and fungi. The present review on microbial degradation pathways and toxicities of degradation intermediates suggests that, among aerobic RDX degradation pathways, the one via denitration may be preferred in a toxicological perspective, and that among anaerobic pathways, those forming 4- nitro-2,4-diazabutanal (NDAB) via ring cleavage of 1-nitroso- 3,5-dinitro-1,3,5-triazinane (MNX) may be toxicologically advantageous owing to its potential mineralization under partial or complete anoxic conditions. These findings provide important information on RDX-degrading microbial pathways, toxicologically most suitable to be stimulated in contaminated fields.

Strategies for engineering plant natural products: the iridoid-derived monoterpene indole alkaloids of Catharanthus roseus.

PubMed

O'Connor, Sarah E

2012-01-01

The manipulation of pathways to make unnatural variants of natural compounds, a process often termed combinatorial biosynthesis, has been robustly successful in prokaryotic systems. The development of approaches to generate new-to-nature compounds from plant-based pathways is, in comparison, much less advanced. Success will depend on the specific chemistry of the pathway, as well as on the suitability of the plant system for transformation and genetic manipulation. As plant pathways are elucidated, and can be heterologously expressed in hosts that are more amenable to genetic manipulation, biosynthetic production of new-to-nature compounds from plant pathways will become more widespread. In this chapter, some of the key strategies that have been developed for metabolic engineering of plant pathways, namely directed biosynthesis, mutasynthesis, and pathway incorporation of engineered enzymes are highlighted. The iridoid-derived monoterpene indole alkaloids from C. roseus, which are the focus of this chapter, provide an excellent system for developing these strategies. Copyright © 2012 Elsevier Inc. All rights reserved.

Overexpressing enzymes of the Ehrlich pathway and deleting genes of the competing pathway in Saccharomyces cerevisiae for increasing 2-phenylethanol production from glucose.

PubMed

Shen, Li; Nishimura, Yuya; Matsuda, Fumio; Ishii, Jun; Kondo, Akihiko

2016-07-01

2-Phenylethanol (2-PE) is a higher aromatic alcohol that is used in the cosmetics and food industries. The budding yeast Saccharomyces cerevisiae is considered to be a suitable host for the industrial production of higher alcohols, including 2-PE. To produce 2-PE from glucose in S. cerevisiae, we searched for suitable 2-keto acid decarboxylase (KDC) and alcohol dehydrogenase (ADH) enzymes of the Ehrlich pathway for overexpression in strain YPH499, and found that overexpression of the ARO10 and/or ADH1 genes increased 2-PE production from glucose. Further, we screened ten BY4741 single-deletion mutants of genes involved in the competing pathways for 2-PE production, and found that strains aro8Δ and aat2Δ displayed increased 2-PE production. Based on these results, we engineered a BY4741 strain that overexpressed ARO10 and contained an aro8Δ deletion, and demonstrated that the strain produced 96 mg/L 2-PE from glucose as the sole carbon source. As this engineered S. cerevisiae strain showed a significant increase in 2-PE production from glucose without the addition of an intermediate carbon substrate, it is a promising candidate for the large-scale production of 2-PE. Copyright © 2016. Published by Elsevier B.V.

Clinical Correlations of Brain Lesion Location in Multiple Sclerosis: Voxel-Based Analysis of a Large Clinical Trial Dataset.

PubMed

Altermatt, Anna; Gaetano, Laura; Magon, Stefano; Häring, Dieter A; Tomic, Davorka; Wuerfel, Jens; Radue, Ernst-Wilhelm; Kappos, Ludwig; Sprenger, Till

2018-05-29

There is a limited correlation between white matter (WM) lesion load as determined by magnetic resonance imaging and disability in multiple sclerosis (MS). The reasons for this so-called clinico-radiological paradox are diverse and may, at least partly, relate to the fact that not just the overall lesion burden, but also the exact anatomical location of lesions predict the severity and type of disability. We aimed at studying the relationship between lesion distribution and disability using a voxel-based lesion probability mapping approach in a very large dataset of MS patients. T2-weighted lesion masks of 2348 relapsing-remitting MS patients were spatially normalized to standard stereotaxic space by non-linear registration. Relations between supratentorial WM lesion locations and disability measures were assessed using a non-parametric ANCOVA (Expanded Disability Status Scale [EDSS]; Multiple Sclerosis Functional Composite, and subscores; Modified Fatigue Impact Scale) or multinomial ordinal logistic regression (EDSS functional subscores). Data from 1907 (81%) patients were included in the analysis because of successful registration. The lesion mapping showed similar areas to be associated with the different disability scales: periventricular regions in temporal, frontal, and limbic lobes were predictive, mainly affecting the posterior thalamic radiation, the anterior, posterior, and superior parts of the corona radiata. In summary, significant associations between lesion location and clinical scores were found in periventricular areas. Such lesion clusters appear to be associated with impairment of different physical and cognitive abilities, probably because they affect commissural and long projection fibers, which are relevant WM pathways supporting many different brain functions.

Differing Presynaptic Contributions to LTP and Associative Learning in Behaving Mice

PubMed Central

Madroñal, Noelia; Gruart, Agnès; Delgado-García, José M.

2009-01-01

The hippocampal CA3-CA1 synapse is an excellent experimental model for studying the interactions between short- and long-term plastic changes taking place following high-frequency stimulation (HFS) of Schaffer collaterals and during the acquisition and extinction of a classical eyeblink conditioning in behaving mice. Input/output curves and a full-range paired-pulse study enabled determining the optimal intensities and inter-stimulus intervals for evoking paired-pulse facilitation (PPF) or depression (PPD) at the CA3-CA1 synapse. Long-term potentiation (LTP) induced by HFS lasted ≈10 days. HFS-induced LTP evoked an initial depression of basal PPF. Recovery of PPF baseline values was a steady and progressive process lasting ≈20 days, i.e., longer than the total duration of the LTP. In a subsequent series of experiments, we checked whether PPF was affected similarly during activity-dependent synaptic changes. Animals were conditioned using a trace paradigm, with a tone as a conditioned stimulus (CS) and an electrical shock to the trigeminal nerve as an unconditioned stimulus (US). A pair of pulses (40 ms interval) was presented to the Schaffer collateral-commissural pathway to evoke field EPSPs (fEPSPs) during the CS-US interval. Basal PPF decreased steadily across conditioning sessions (i.e., in the opposite direction to that during LTP), reaching a minimum value during the 10th conditioning session. Thus, LTP and classical eyeblink conditioning share some presynaptic mechanisms, but with an opposite evolution. Furthermore, PPF and PPD might play a homeostatic role during long-term plastic changes at the CA3-CA1 synapse. PMID:19636387

Network design and analysis for multi-enzyme biocatalysis.

PubMed

Blaß, Lisa Katharina; Weyler, Christian; Heinzle, Elmar

2017-08-10

As more and more biological reaction data become available, the full exploration of the enzymatic potential for the synthesis of valuable products opens up exciting new opportunities but is becoming increasingly complex. The manual design of multi-step biosynthesis routes involving enzymes from different organisms is very challenging. To harness the full enzymatic potential, we developed a computational tool for the directed design of biosynthetic production pathways for multi-step catalysis with in vitro enzyme cascades, cell hydrolysates and permeabilized cells. We present a method which encompasses the reconstruction of a genome-scale pan-organism metabolic network, path-finding and the ranking of the resulting pathway candidates for proposing suitable synthesis pathways. The network is based on reaction and reaction pair data from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the thermodynamics calculator eQuilibrator. The pan-organism network is especially useful for finding the most suitable pathway to a target metabolite from a thermodynamic or economic standpoint. However, our method can be used with any network reconstruction, e.g. for a specific organism. We implemented a path-finding algorithm based on a mixed-integer linear program (MILP) which takes into account both topology and stoichiometry of the underlying network. Unlike other methods we do not specify a single starting metabolite, but our algorithm searches for pathways starting from arbitrary start metabolites to a target product of interest. Using a set of biochemical ranking criteria including pathway length, thermodynamics and other biological characteristics such as number of heterologous enzymes or cofactor requirement, it is possible to obtain well-designed meaningful pathway alternatives. In addition, a thermodynamic profile, the overall reactant balance and potential side reactions as well as an SBML file for visualization are generated for each pathway alternative. We present an in silico tool for the design of multi-enzyme biosynthetic production pathways starting from a pan-organism network. The method is highly customizable and each module can be adapted to the focus of the project at hand. This method is directly applicable for (i) in vitro enzyme cascades, (ii) cell hydrolysates and (iii) permeabilized cells.

Identification of altered pathways in breast cancer based on individualized pathway aberrance score.

PubMed

Shi, Sheng-Hong; Zhang, Wei; Jiang, Jing; Sun, Long

2017-08-01

The objective of the present study was to identify altered pathways in breast cancer based on the individualized pathway aberrance score (iPAS) method combined with the normal reference (nRef). There were 4 steps to identify altered pathways using the iPAS method: Data preprocessing conducted by the robust multi-array average (RMA) algorithm; gene-level statistics based on average Z ; pathway-level statistics according to iPAS; and a significance test dependent on 1 sample Wilcoxon test. The altered pathways were validated by calculating the changed percentage of each pathway in tumor samples and comparing them with pathways from differentially expressed genes (DEGs). A total of 688 altered pathways with P<0.01 were identified, including kinesin (KIF)- and polo-like kinase (PLK)-mediated events. When the percentage of change reached 50%, 310 pathways were involved in the total 688 altered pathways, which may validate the present results. In addition, there were 324 DEGs and 155 common genes between DEGs and pathway genes. DEGs and common genes were enriched in the same 9 significant terms, which also were members of altered pathways. The iPAS method was suitable for identifying altered pathways in breast cancer. Altered pathways (such as KIF and PLK mediated events) were important for understanding breast cancer mechanisms and for the future application of customized therapeutic decisions.

[Cerebral artery thrombosis in pregnancy].

PubMed

Charco Roca, L M; Ortiz Sanchez, V E; Hernandez Gutierrez-Manchon, O; Quesada Villar, J; Bonmatí García, L; Rubio Postigo, G

2015-11-01

A 28 year old woman, ASA I, who, in the final stages of her pregnancy presented with signs of neural deficit that consisted of distortion of the oral commissure, dysphagia, dysarthria, and weakness on the left side of the body. She was diagnosed with thrombosis in a segment of the right middle cerebral artery which led to an ischemic area in the right frontal lobe. Termination of pregnancy and conservative treatment was decided, with good resolution of the symptoms. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Ultrasonic Doppler measurement of renal artery blood flow

NASA Technical Reports Server (NTRS)

Freund, W. R.; Beaver, W. L.; Meindl, J. D.

1976-01-01

Studies were made of (1) blood flow redistribution during lower body negative pressure (LBNP), (2) the profile of blood flow across the mitral annulus of the heart (both perpendicular and parallel to the commissures), (3) testing and evaluation of a number of pulsed Doppler systems, (4) acute calibration of perivascular Doppler transducers, (5) redesign of the mitral flow transducers to improve reliability and ease of construction, and (6) a frequency offset generator designed for use in distinguishing forward and reverse components of blood flow by producing frequencies above and below the offset frequency. Finally methodology was developed and initial results were obtained from a computer analysis of time-varying Doppler spectra.

Purification of Lysosomes Using Supraparamagnetic Iron Oxide Nanoparticles (SPIONs).

PubMed

Rofe, Adam P; Pryor, Paul R

2016-04-01

Lysosomes can be rapidly isolated from tissue culture cells using supraparamagnetic iron oxide particles (SPIONs). In this protocol, colloidal iron dextran (FeDex) particles, a type of SPION, are taken up by cultured mouse macrophage cells via the endocytic pathway. The SPIONs accumulate in lysosomes, the end point of the endocytic pathway, permitting the lysosomes to be isolated magnetically. The purified lysosomes are suitable for in vitro fusion assays or for proteomic analysis. © 2016 Cold Spring Harbor Laboratory Press.

Managed Entry Agreements for Pharmaceuticals in the Context of Adaptive Pathways in Europe.

PubMed

Bouvy, Jacoline C; Sapede, Claudine; Garner, Sarah

2018-01-01

As per the EMA definition, adaptive pathways is a scientific concept for the development of medicines which seeks to facilitate patient access to promising medicines addressing high unmet need through a prospectively planned approach in a sustainable way. This review reports the findings of activities undertaken by the ADAPT-SMART consortium to identify enablers and explore the suitability of managed entry agreements for adaptive pathways products in Europe. We found that during 2006-2016 outcomes-based managed entry agreements were not commonly used for products with a conditional marketing authorization or authorized under exceptional circumstances. The barriers and enablers to develop workable managed entry agreements models for adaptive pathways products were discussed through interviews and a multi-stakeholder workshop with a number of recommendations made in this paper.

Maximizing the efficiency of multienzyme process by stoichiometry optimization.

PubMed

Dvorak, Pavel; Kurumbang, Nagendra P; Bendl, Jaroslav; Brezovsky, Jan; Prokop, Zbynek; Damborsky, Jiri

2014-09-05

Multienzyme processes represent an important area of biocatalysis. Their efficiency can be enhanced by optimization of the stoichiometry of the biocatalysts. Here we present a workflow for maximizing the efficiency of a three-enzyme system catalyzing a five-step chemical conversion. Kinetic models of pathways with wild-type or engineered enzymes were built, and the enzyme stoichiometry of each pathway was optimized. Mathematical modeling and one-pot multienzyme experiments provided detailed insights into pathway dynamics, enabled the selection of a suitable engineered enzyme, and afforded high efficiency while minimizing biocatalyst loadings. Optimizing the stoichiometry in a pathway with an engineered enzyme reduced the total biocatalyst load by an impressive 56 %. Our new workflow represents a broadly applicable strategy for optimizing multienzyme processes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[MRI in congenital nystagmus].

PubMed

Denis, D; Girard, N; Toesca, E; Zanin, E; Gambarelli, N; Lebranchu, P; Mancini, J

2010-03-01

Congenital nystagmus (CN) that is present by the age of 3 months is the most common form of nystagmus in childhood. We present a prospective study (2001-2008) in which we report imaging findings in 48 children with CN. Twenty-six boys and 22 girls with CN underwent a complete ophthalmologic assessment and a cerebral MRI (mean age of examination under general anesthesia: 11 months). Three CN groups were formed: neurologic (n=27), sensory visual disturbance (n=14), and isolated (n=7). Cerebral MRI was interpreted by the same pediatric neuroradiologist (NG). Of the children studied, 98 % were born at term. The MRI abnormalities were classified as morphologic abnormalities (malformative or nonmalformative) and as signal abnormalities. The location of brain abnormalities was within the posterior fossa, (brain stem, cerebellum, dental nuclei, cisterna magna) and the cerebral hemisphere (white matter, perivascular spaces, midline commissures, basal ganglia). Pendular nystagmus was prevalent in sensory and neurologic nystagmus. On fundus examination, optic disc abnormalities were present in 70 % (19) of neurologic CN and associated with white matter abnormalities of the optic radiations in 40 % of cases. On MRI, malformative morphologic abnormalities were present in 27 cases, nonmalformative abnormalities were found in 67, and signal abnormalities in 68. Within the brain stem, signal abnormalities were found as a cockade appearance of the posterior pons in the reticular regions (neurologic n=14, sensory n=6, isolated n=3). Other bright (most frequent) signal abnormalities were found within the dentate nuclei of the posterior fossa (neurologic n=10, sensory n=3, isolated n=3) and the cerebral white matter (neurologic n=17, sensory n=7, isolated n=5) of which 24 (neurologic n=15, sensory n=5, isolated n=4) involved the optic radiations. Most of these abnormalities were related and were seen most frequently in neurologic nystagmus. The most frequent association was signal abnormalities of the white matter, ventricular dilatation, and dilatation of the perivascular spaces (60.4 %) (neurologic n=13, sensory n=6). This study showed the fundamental contribution of the cerebral MRI in CN. Cerebral abnormalities were found at the pathways for ocular motility, particularly at the saccadic pathways.

Managed Entry Agreements for Pharmaceuticals in the Context of Adaptive Pathways in Europe

PubMed Central

Bouvy, Jacoline C.; Sapede, Claudine; Garner, Sarah

2018-01-01

As per the EMA definition, adaptive pathways is a scientific concept for the development of medicines which seeks to facilitate patient access to promising medicines addressing high unmet need through a prospectively planned approach in a sustainable way. This review reports the findings of activities undertaken by the ADAPT-SMART consortium to identify enablers and explore the suitability of managed entry agreements for adaptive pathways products in Europe. We found that during 2006–2016 outcomes-based managed entry agreements were not commonly used for products with a conditional marketing authorization or authorized under exceptional circumstances. The barriers and enablers to develop workable managed entry agreements models for adaptive pathways products were discussed through interviews and a multi-stakeholder workshop with a number of recommendations made in this paper. PMID:29636692

Glycobiology in yeast: production of bio-ative biopolymers and small molecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scheller, Henrik

The accomplished goals of the CRADA were the establishment of a yeast strain capable of producing levels of vanillin suitable for commercial production and the identification of novel glycosyltransferases to construct the biosynthetic pathway of a gum Arabic-variant in yeast.

Anovulvar cleft and vaginal prolapse-hyperplasia in a bitch.

PubMed

Mostachio, G Q; Vicente, W R R; Cardilli, D J; Pires, E A; Toniollo, G H

2007-12-01

This report presents the case of a nine-month-old bitch with incomplete occlusion of the skin and mucosa between the anus and dorsal commissure of the vulva. This anomaly, known as anovulvar cleft, was associated with a vaginal prolapse-hyperplasia. Anovulvar cleft is a rare condition in bitches and is caused by incomplete closure of the dorsal urogenital folds. Anovulvar cleft can lead to clitoritis, abrasion, dryness and devitalisation of the smooth exposed mucosa. Surgery can correct the condition. In the present study, surgical resection of the hyperplasic vaginal tissue associated with perineoplasty using an inverted V-shaped incision showed excellent results. An ovariohysterectomy was also performed to prevent recurrence of the vaginal prolapse-hyperplasia.

Efferent projections of the septum in the Tegu lizard, Tupinambis nigropunctatus.

PubMed

Sligar, C M; Voneida, T J

1981-09-01

A H3 proline or H3 leucine mixture was injected into the septal region of the Tegu lizard in order to determine its efferent projections. The brains were processed according to standard autoradiographic technique and counterstained with cresyl violet. Septal projections were limited to either telencephalic or diencephalic areas. Intratelencephalic projections consisted of efferents to medial pallium, nucleus accumbens, bed nucleus of the anterior commissure, preoptic area and septum itself. Fibers entering the diencephalon projected to medial habenular nucleus, dorsomedial thalamic nucleus, dorsolateral thalamic area, periventricular nucleus of the hypothalamus, lateral hypothalamic area and mammillary nucleus. The results are discussed in relation to the efferent projections of the septum in other vertebrates.

Dentition of the apron ray Discopyge tschudii (Elasmobranchii: Narcinidae).

PubMed

Spath, M C; Deli Antoni, M; Delpiani, G

2017-10-01

The present study provides quantitative and qualitative analyses of the dentition of Discopyge tschudii. Overall, 193 individuals (99 males and 94 females) of D. tschudii were collected on scientific trawl surveys conducted by the National Institute for Fisheries Research and Development (INIDEP) and commercial vessels in Argentina. Discopyge tschudii has rhombic-shaped teeth, arranged in a semipavement-like dentition; each tooth has an erect cusp slightly inclined posteriorly and holaulachorized root. Mature males have greater tooth lengths than females and immature specimens. Discopyge tschudii exhibits dignathic homodonty and gradient monognathic heterodonty where teeth of the commissural row are shorter than those of the symphyseal and internal rows. © 2017 The Fisheries Society of the British Isles.

Novel magnet-retained prosthetic system for facial reconstruction.

PubMed

Ahmed, Mostafa M; Piper, James M; Hansen, Nancy A; Sutton, Alan J; Schmalbach, Cecelia E

2014-01-01

Traumatic facial defects negatively impact speech, mastication, deglutition, dental hygiene, and psychosocial well-being. Reconstruction must address restoration of function and aesthetics to provide quality of life. This report describes soft-tissue reconstruction using a novel magnet-retained facial prosthesis without osseointegrated abutments, performed in a patient after traumatic loss of the entire left lower part of the face, including lips, commissure, and mentum. This reconstructive technique successfully addressed the cosmetic defect while also restoring function with respect to speech and oral nutrition. For this reason, magnet-retained facial prosthesis should be added to free tissue transfer and regional flaps as a reasonable option in the reconstructive algorithm for complex soft-tissue defects of the lower face.

Transcallosal transfer of information and functional asymmetry of the human brain.

PubMed

Nowicka, Anna; Tacikowski, Pawel

2011-01-01

The corpus callosum is the largest commissure in the brain and acts as a "bridge" of nerve fibres connecting the two cerebral hemispheres. It plays a crucial role in interhemispheric integration and is responsible for normal communication and cooperation between the two hemispheres. Evolutionary pressures guiding brain size are accompanied by reduced interhemispheric and enhanced intrahemispheric connectivity. Some lines of evidence suggest that the speed of transcallosal conduction is limited in large brains (e.g., in humans), thus favouring intrahemispheric processing and brain lateralisation. Patterns of directional symmetry/asymmetry of transcallosal transfer time may be related to the degree of brain lateralisation. Neural network modelling and electrophysiological studies on interhemispheric transmission provide data supporting this supposition.

Formate Assimilation: The Metabolic Architecture of Natural and Synthetic Pathways.

PubMed

Bar-Even, Arren

2016-07-19

Formate may become an ideal mediator between the physicochemical and biological realms, as it can be produced efficiently from multiple available sources, such as electricity and biomass, and serve as one of the simplest organic compounds for providing both carbon and energy to living cells. However, limiting the realization of formate as a microbial feedstock is the low diversity of formate-fixing enzymes and thereby the small number of naturally occurring formate-assimilation pathways. Here, the natural enzymes and pathways supporting formate assimilation are presented and discussed together with proposed synthetic routes that could permit growth on formate via existing as well as novel formate-fixing reactions. By considering such synthetic routes, the diversity of metabolic solutions for formate assimilation can be expanded dramatically, such that different host organisms, cultivation conditions, and desired products could be matched with the most suitable pathway. Astute application of old and new formate-assimilation pathways may thus become a cornerstone in the development of sustainable strategies for microbial production of value-added chemicals.

The Biological Connection Markup Language: a SBGN-compliant format for visualization, filtering and analysis of biological pathways.

PubMed

Beltrame, Luca; Calura, Enrica; Popovici, Razvan R; Rizzetto, Lisa; Guedez, Damariz Rivero; Donato, Michele; Romualdi, Chiara; Draghici, Sorin; Cavalieri, Duccio

2011-08-01

Many models and analysis of signaling pathways have been proposed. However, neither of them takes into account that a biological pathway is not a fixed system, but instead it depends on the organism, tissue and cell type as well as on physiological, pathological and experimental conditions. The Biological Connection Markup Language (BCML) is a format to describe, annotate and visualize pathways. BCML is able to store multiple information, permitting a selective view of the pathway as it exists and/or behave in specific organisms, tissues and cells. Furthermore, BCML can be automatically converted into data formats suitable for analysis and into a fully SBGN-compliant graphical representation, making it an important tool that can be used by both computational biologists and 'wet lab' scientists. The XML schema and the BCML software suite are freely available under the LGPL for download at http://bcml.dc-atlas.net. They are implemented in Java and supported on MS Windows, Linux and OS X.

Long-term plasticity in identified hippocampal GABAergic interneurons in the CA1 area in vivo.

PubMed

Lau, Petrina Yau-Pok; Katona, Linda; Saghy, Peter; Newton, Kathryn; Somogyi, Peter; Lamsa, Karri P

2017-05-01

Long-term plasticity is well documented in synapses between glutamatergic principal cells in the cortex both in vitro and in vivo. Long-term potentiation (LTP) and -depression (LTD) have also been reported in glutamatergic connections to hippocampal GABAergic interneurons expressing parvalbumin (PV+) or nitric oxide synthase (NOS+) in brain slices, but plasticity in these cells has not been tested in vivo. We investigated synaptically-evoked suprathreshold excitation of identified hippocampal neurons in the CA1 area of urethane-anaesthetized rats. Neurons were recorded extracellularly with glass microelectrodes, and labelled with neurobiotin for anatomical analyses. Single-shock electrical stimulation of afferents from the contralateral CA1 elicited postsynaptic action potentials with monosynaptic features showing short delay (9.95 ± 0.41 ms) and small jitter in 13 neurons through the commissural pathway. Theta-burst stimulation (TBS) generated LTP of the synaptically-evoked spike probability in pyramidal cells, and in a bistratified cell and two unidentified fast-spiking interneurons. On the contrary, PV+ basket cells and NOS+ ivy cells exhibited either LTD or LTP. An identified axo-axonic cell failed to show long-term change in its response to stimulation. Discharge of the cells did not explain whether LTP or LTD was generated. For the fast-spiking interneurons, as a group, no correlation was found between plasticity and local field potential oscillations (1-3 or 3-6 Hz components) recorded immediately prior to TBS. The results demonstrate activity-induced long-term plasticity in synaptic excitation of hippocampal PV+ and NOS+ interneurons in vivo. Physiological and pathological activity patterns in vivo may generate similar plasticity in these interneurons.

Distribution and physiological effects of B-type allatostatins (myoinhibitory peptides, MIPs) in the stomatogastric nervous system of the crab Cancer borealis.

PubMed

Szabo, Theresa M; Chen, Ruibing; Goeritz, Marie L; Maloney, Ryan T; Tang, Lamont S; Li, Lingjun; Marder, Eve

2011-09-01

The crustacean stomatogastric ganglion (STG) is modulated by a large number of amines and neuropeptides that are found in descending pathways from anterior ganglia or reach the STG via the hemolymph. Among these are the allatostatin (AST) B types, also known as myoinhibitory peptides (MIPs). We used mass spectrometry to determine the sequences of nine members of the AST-B family of peptides that were found in the stomatogastric nervous system of the crab Cancer borealis. We raised an antibody against Cancer borealis allatostatin-B1 (CbAST-B1; VPNDWAHFRGSWa) and used it to map the distribution of CbAST-B1-like immunoreactivity (-LI) in the stomatogastric nervous system. CbAST-B1-LI was found in neurons and neuropil in the commissural ganglia (CoGs), in somata in the esophageal ganglion (OG), in fibers in the stomatogastric nerve (stn), and in neuropilar processes in the STG. CbAST-B1-LI was blocked by preincubation with 10(-6) M CbAST-B1 and was partially blocked by lower concentrations. Electrophysiological recordings of the effects of CbAST-B1, CbAST-B2, and CbAST-B3 on the pyloric rhythm of the STG showed that all three peptides inhibited the pyloric rhythm in a state-dependent manner. Specifically, all three peptides at 10(-8) M significantly decreased the frequency of the pyloric rhythm when the initial frequency of the pyloric rhythm was below 0.6 Hz. These data suggest important neuromodulatory roles for the CbAST-B family in the stomatogastric nervous system. Copyright © 2011 Wiley-Liss, Inc.

Distribution and physiological effects of B-type allatostatins (myoinhibitory peptides, MIPs) in the stomatogastric nervous system of the crab, Cancer borealis

PubMed Central

Szabo, Theresa M.; Chen, Ruibing; Goeritz, Marie L.; Maloney, Ryan T.; Tang, Lamont S.; Li, Lingjun; Marder, Eve

2011-01-01

The crustacean stomatogastric ganglion (STG) is modulated by a large number of amines and neuropeptides that are found in descending pathways from anterior ganglia or reach the STG via the hemolymph. Among these are the allatostatin (AST) – B types also known as myoinhibitory peptides (MIPs). We used mass spectrometry to determine the sequences of nine members of the AST-B family of peptides that were found in the stomatogastric nervous system of the crab, Cancer borealis. We raised an antibody against Cancer borealis Allatostatin-B1 (CbAST-B1) (VPNDWAHFRGSWa) and used it to map the distribution of CbAST-B1-like immunoreactivity (-LI) in the stomatogastric nervous system. CbAST-B1-LI was found in neurons and neuropil in the commissural ganglia (CoGs), in somata in the esophageal ganglion (OG), in fibers in the stomatogastric nerve (stn), and in neuropilar processes in the STG. CbAST-B1-LI was blocked by preincubation with 10-6 M CbAST-B1, and partially blocked by lower concentrations. Electrophysiological recordings of the effects of CbAST-B1, CbAST-B2, and CbAST-B3 on the pyloric rhythm of the STG showed that all three peptides inhibited the pyloric rhythm in a state-dependent manner. Specifically, all three peptides at 10-8 M significantly decreased the frequency of the pyloric rhythm when the initial frequency of the pyloric rhythm was below 0.6 Hz. These data suggest important neuromodulatory roles for the CbAST-B family in the stomatogastric nervous system. PMID:21491432

Special Analysis for the Disposal of the Sandia National Laboratory Classified Macroencapsulated Mixed Waste at the Area 5 Radioactive Waste Management Site, Nevada National Security Site, Nye County, Nevada

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gregory, Louis B.

This special analysis evaluates whether the Sandia National Laboratory (SNL) Classified Macroencapsulated Mixed Waste stream (ASLA000001007, Revision 4) is suitable for disposal by shallow land burial (SLB) at the Area 5 Radioactive Waste Management Site (RWMS) at the Nevada National Security Site (NNSS). The SNL Classified Macroencapsulated Mixed Waste stream consists of debris from classified nuclear weapons components (SNL 2015). The SNL Classified Macroencapsulated Mixed Waste stream required a special analysis due to tritium (3H) exceeding the NNSS Waste Acceptance Criteria (WAC) Action Levels (U.S. Department of Energy, National Nuclear Security Administration Nevada Field Office [NNSA/NFO] 2015). The SNL Classifiedmore » Macroencapsulated Mixed Waste stream had no significant effect on the maximum mean and 95th percentile results for the resident air pathway and all-pathways annual total effective dose (TED). The SNL Classified Macroencapsulated Mixed Waste stream increases the mean air pathway and all-pathways annual TED from approximately 100 to 200 years after closure. Addition of the SNL Classified Macroencapsulated Mixed Waste stream inventory shifts the maximum TED to approximately 100 years after closure and increases the TED for several alternative exposure scenarios. The maximum mean and the 95th percentile 222Rn flux density remain less than the performance objective throughout the compliance period. The SNL Classified Macroencapsulated Mixed Waste stream is suitable for disposal by SLB at the Area 5 RWMS. The waste stream is recommended for approval without conditions.« less

Vulnerability of field crops to midcentury temperature changes and yield effects in the Southwestern USA

USDA-ARS?s Scientific Manuscript database

Increased temperatures in the Southwestern United States will impact future crop production via multiple pathways. We used four methods to provide an illustrative analysis of midcentury temperature impacts to eight field crops. By midcentury, cropland area thermally suitable for maize cultivation is...

Sensitivity of neuroprogenitor cells to chemical-induced apoptosis using a multiplexed assay suitable for high-throughput screening*

EPA Science Inventory

AbstractHigh-throughput methods are useful for rapidly screening large numbers of chemicals for biological activity, including the perturbation of pathways that may lead to adverse cellular effects. In vitro assays for the key events of neurodevelopment, including apoptosis, may ...

Career Pathways of Science, Engineering and Technology Research Postgraduates

ERIC Educational Resources Information Center

Giles, Marnie; Ski, Chantal; Vrdoljak, Davorin

2009-01-01

Suitably qualified scientists and engineers are essential for research and development, innovation and, in turn, the growth of the economy. Science, engineering and technology skills are therefore necessary for Australia to remain competitive in a global market. This article reports findings from a nationwide study investigating the career…

Invasive alien plant species dynamics in the Himalayan region under climate change.

PubMed

Lamsal, Pramod; Kumar, Lalit; Aryal, Achyut; Atreya, Kishor

2018-01-25

Climate change will impact the dynamics of invasive alien plant species (IAPS). However, the ability of IAPS under changing climate to invade mountain ecosystems, particularly the Himalayan region, is less known. This study investigates the current and future habitat of five IAPS of the Himalayan region using MaxEnt and two representative concentration pathways (RCPs). Two invasive species, Ageratum conyzoides and Parthenium hysterophorus, will lose overall suitable area by 2070, while Ageratina adenophora, Chromolaena odorata and Lantana camara will gain suitable areas and all of them will retain most of the current habitat as stable. The southern Himalayan foothills will mostly conserve species ecological niches, while suitability of all the five species will decrease with increasing elevation. Such invasion dynamics in the Himalayan region could have impacts on numerous ecosystems and their biota, ecosystem services and human well-being. Trans-boundary response strategies suitable to the local context of the region could buffer some of the likely invasion impacts.

Shifts of heat availability and stressful temperatures in Russian Federation result in gains and losses of wheat thermal suitability

NASA Astrophysics Data System (ADS)

Di Paola, Arianna; Caporaso, Luca; Santini, Monia; Di Paola, Francesco; Vasenev, Ivan; Valentini, Riccardo

2017-04-01

Climate changes are likely to shift the suitability of lands devoted to cropping systems. We explored the past-to-future thermal suitability of Russian Federation for wheat (Triticum aestivum) culture through an ensemble of bias corrected CMIP5-GCMs outputs considering two representative concentration pathways (RCP 4.5 and 8.5). Thermal suitability assesses where wheat heat requirement, counted from suggested sowing dates, is satisfied without the occurrence of stressful hot and frost temperatures. Thermal requirement was estimated by means of phenological observations on soft wheat involving different wheat cultivar collected in different regions of Russian Federation, Azerbaidhan, Kazakhstan and Tadzhikistan, whilst stressful temperatures were taken from a literature survey. Results showed projected geographical shift of heat resource toward the north-eastern regions, currently mainly covered by forests and croplands, but also an increase of very hot temperatures in the most productive areas of the southern regions. Gains and losses were then quantified and discussed from both agronomical and climatic perspective.

Validation of In utero Tractography of Human Fetal Commissural and Internal Capsule Fibers with Histological Structure Tensor Analysis

PubMed Central

Mitter, Christian; Jakab, András; Brugger, Peter C.; Ricken, Gerda; Gruber, Gerlinde M.; Bettelheim, Dieter; Scharrer, Anke; Langs, Georg; Hainfellner, Johannes A.; Prayer, Daniela; Kasprian, Gregor

2015-01-01

Diffusion tensor imaging (DTI) and tractography offer the unique possibility to visualize the developing white matter macroanatomy of the human fetal brain in vivo and in utero and are currently under investigation for their potential use in the diagnosis of developmental pathologies of the human central nervous system. However, in order to establish in utero DTI as a clinical imaging tool, an independent comparison between macroscopic imaging and microscopic histology data in the same subject is needed. The present study aimed to cross-validate normal as well as abnormal in utero tractography results of commissural and internal capsule fibers in human fetal brains using postmortem histological structure tensor (ST) analysis. In utero tractography findings from two structurally unremarkable and five abnormal fetal brains were compared to the results of postmortem ST analysis applied to digitalized whole hemisphere sections of the same subjects. An approach to perform ST-based deterministic tractography in histological sections was implemented to overcome limitations in correlating in utero tractography to postmortem histology data. ST analysis and histology-based tractography of fetal brain sections enabled the direct assessment of the anisotropic organization and main fiber orientation of fetal telencephalic layers on a micro- and macroscopic scale, and validated in utero tractography results of corpus callosum and internal capsule fiber tracts. Cross-validation of abnormal in utero tractography results could be achieved in four subjects with agenesis of the corpus callosum (ACC) and in two cases with malformations of internal capsule fibers. In addition, potential limitations of current DTI-based in utero tractography could be demonstrated in several brain regions. Combining the three-dimensional nature of DTI-based in utero tractography with the microscopic resolution provided by histological ST analysis may ultimately facilitate a more complete morphologic characterization of axon guidance disorders at prenatal stages of human brain development. PMID:26732460

Skeletal morphology and development of the olfactory region of Spea (Anura: Scaphiopodidae)

PubMed Central

Pugener, L A; Maglia, A M

2007-01-01

The nasal capsules of anurans are formed by an intricate set of sac-like cavities that house the olfactory organ and constitute the beginning of the respiratory system. In tadpoles, nasal capsules do not have a respiratory function, but each is composed of a single soft tissue cavity lined with olfactory epithelium. Our study has revealed that in Spea the nasal cartilages and septomaxillae are de novo adult structures that form dorsal to the larval skeleton of the ethmoid region. The only element of the adult nasal capsule that is partially derived from the larval skeleton is the solum nasi. Development of the nasal skeleton begins at about Gosner Stage 31, with chondrification of the septum nasi and lamina orbitonasalis. The alary cartilage and superior prenasal cartilage are the first of the anterior nasal cartilages to chondrify at Gosner Stage 37. By Gosner Stages 40/41, the ethmoid region is composed of the larval structures ventrally and the adult structures dorsally. By Stage 44, the larval structures have eroded. The adult nasal capsule is characterized by: (1) a septum nasi that projects ventrally beyond the plane of the nasal floor; (2) a paranasal commissure that forms the ventral margin of the fenestra nasolateralis; and (3) a large skeletal support for the eminentia olfactoria formed by the nasal floor and vomer. The timing of chondrification of the anterior nasal cartilages and the development of the postnasal wall, inferior prenasal cartilage, fenestra nasolateralis, and paranasal commissure are discussed and compared with those of other anuran species. This study also includes a discussion of the morphology of the skeletal support for the eminentia olfactoria, a structure best developed in distinctly ground-dwelling frogs such as spadefoot toads. Finally, we propose a more precise restriction of the terminology that is used to designate the posterior structures of the olfactory region of anurans. PMID:18045351

Neurochemical, morphologic, and laminar characterization of cortical projection neurons in the cingulate motor areas of the macaque monkey

NASA Technical Reports Server (NTRS)

Nimchinsky, E. A.; Hof, P. R.; Young, W. G.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

1996-01-01

The primate cingulate gyrus contains multiple cortical areas that can be distinguished by several neurochemical features, including the distribution of neurofilament protein-enriched pyramidal neurons. In addition, connectivity and functional properties indicate that there are multiple motor areas in the cortex lining the cingulate sulcus. These motor areas were targeted for analysis of potential interactions among regional specialization, connectivity, and cellular characteristics such as neurochemical profile and morphology. Specifically, intracortical injections of retrogradely transported dyes and intracellular injection were combined with immunocytochemistry to investigate neurons projecting from the cingulate motor areas to the putative forelimb region of the primary motor cortex, area M1. Two separate groups of neurons projecting to area M1 emanated from the cingulate sulcus, one anterior and one posterior, both of which furnished commissural and ipsilateral connections with area M1. The primary difference between the two populations was laminar origin, with the anterior projection originating largely in deep layers, and the posterior projection taking origin equally in superficial and deep layers. With regard to cellular morphology, the anterior projection exhibited more morphologic diversity than the posterior projection. Commissural projections from both anterior and posterior fields originated largely in layer VI. Neurofilament protein distribution was a reliable tool for localizing the two projections and for discriminating between them. Comparable proportions of the two sets of projection neurons contained neurofilament protein, although the density and distribution of the total population of neurofilament protein-enriched neurons was very different in the two subareas of origin. Within a projection, the participating neurons exhibited a high degree of morphologic heterogeneity, and no correlation was observed between somatodendritic morphology and neurofilament protein content. Thus, although the neurons that provide the anterior and posterior cingulate motor projections to area M1 differ morphologically and in laminar origin, their neurochemical profiles are similar with respect to neurofilament protein. This suggests that neurochemical phenotype may be a more important unifying feature for corticocortical projections than morphology.

Clinical brain MR imaging prescriptions in Talairach space: technologist- and computer-driven methods.

PubMed

Weiss, Kenneth L; Pan, Hai; Storrs, Judd; Strub, William; Weiss, Jane L; Jia, Li; Eldevik, O Petter

2003-05-01

Variability in patient head positioning may yield substantial interstudy image variance in the clinical setting. We describe and test three-step technologist and computer-automated algorithms designed to image the brain in a standard reference system and reduce variance. Triple oblique axial images obtained parallel to the Talairach anterior commissure (AC)-posterior commissure (PC) plane were reviewed in a prospective analysis of 126 consecutive patients. Requisite roll, yaw, and pitch correction, as three authors determined independently and subsequently by consensus, were compared with the technologists' actual graphical prescriptions and those generated by a novel computer automated three-step (CATS) program. Automated pitch determinations generated with Statistical Parametric Mapping '99 (SPM'99) were also compared. Requisite pitch correction (15.2 degrees +/- 10.2 degrees ) far exceeded that for roll (-0.6 degrees +/- 3.7 degrees ) and yaw (-0.9 degrees +/- 4.7 degrees ) in terms of magnitude and variance (P <.001). Technologist and computer-generated prescriptions substantially reduced interpatient image variance with regard to roll (3.4 degrees and 3.9 degrees vs 13.5 degrees ), yaw (0.6 degrees and 2.5 degrees vs 22.3 degrees ), and pitch (28.6 degrees, 18.5 degrees with CATS, and 59.3 degrees with SPM'99 vs 104 degrees ). CATS performed worse than the technologists in yaw prescription, and it was equivalent in roll and pitch prescriptions. Talairach prescriptions better approximated standard CT canthomeatal angulations (9 degrees vs 24 degrees ) and provided more efficient brain coverage than that of routine axial imaging. Brain MR prescriptions corrected for direct roll, yaw, and Talairach AC-PC pitch can be readily achieved by trained technologists or automated computer algorithms. This ability will substantially reduce interpatient variance, allow better approximation of standard CT angulation, and yield more efficient brain coverage than that of routine clinical axial imaging.

Lesion of the commissural nucleus of the solitary tract/A2 noradrenergic neurons facilitates the activation of angiotensinergic mechanisms in response to hemorrhage.

PubMed

Freiria-Oliveira, A H; Blanch, G T; De Paula, P M; Menani, J V; Colombari, D S A

2013-12-19

In the present study, we investigated the effects of lesions of A2 neurons of the commissural nucleus of the solitary tract (cNTS) alone or combined with the blockade of angiotensinergic mechanisms on the recovery of arterial pressure (AP) to hemorrhage in conscious rats. Male Holtzman rats (280-320g) received an injection of anti-dopamine-beta-hydroxylase-saporin (12.6ng/60nl; cNTS/A2-lesion, n=28) or immunoglobulin G (IgG)-saporin (12.6ng/60nl, sham, n=24) into the cNTS and 15-21days later had a stainless steel cannula implanted in the lateral ventricle. After 6days, rats were submitted to hemorrhage (four blood withdrawals, 2ml/300g of body weight every 10min). Both cNTS/A2-lesioned and sham rats had similar hypotension to hemorrhage (-62±7 and -73±7mmHg, respectively), however cNTS/A2-lesioned rats rapidly recovered from hypotension (-5±3mmHg at 30min), whereas sham rats did not completely recover until the end of the recording (-20±3mmHg at 60min). Losartan (angiotensin type 1 receptor antagonist) injected intracerebroventricularly (100μg/1μl) or intravenously (i.v.) (10mg/kg of body weight) impaired the recovery of AP in cNTS/A2-lesioned rats (-24±6 and -35±7mmHg at 30min, respectively). In sham rats, only i.v. losartan affected the recovery of AP (-39±6mmHg at 60min). The results suggest that lesion of the A2 neurons in the cNTS facilitates the activation of the angiotensinergic pressor mechanisms in response to hemorrhage. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Development of the nervous system in Phoronopsis harmeri (Lophotrochozoa, Phoronida) reveals both deuterostome- and trochozoan-like features

PubMed Central

2012-01-01

Background Inferences concerning the evolution of invertebrate nervous systems are often hampered by the lack of a solid data base for little known but phylogenetically crucial taxa. In order to contribute to the discussion concerning the ancestral neural pattern of the Lophotrochozoa (a major clade that includes a number of phyla that exhibit a ciliated larva in their life cycle), we investigated neurogenesis in Phoronopsis harmeri, a member of the poorly studied Phoronida, by using antibody staining against serotonin and FMRFamide in combination with confocal microscopy and 3D reconstruction software. Results The larva of Phoronopsis harmeri exhibits a highly complex nervous system, including an apical organ that consists of four different neural cell types, such as numerous serotonin-like immunoreactive flask-shaped cells. In addition, serotonin- and FMRFamide-like immunoreactive bi- or multipolar perikarya that give rise to a tentacular neurite bundle which innervates the postoral ciliated band are found. The preoral ciliated band is innervated by marginal serotonin-like as well as FMRFamide-like immunoreactive neurite bundles. The telotroch is innervated by two neurite bundles. The oral field is the most densely innervated area and contains ventral and ventro-lateral neurite bundles as well as several groups of perikarya. The digestive system is innervated by both serotonin- and FMRFamide-like immunoreactive neurites and perikarya. Importantly, older larvae of P. harmeri show a paired ventral neurite bundle with serial commissures and perikarya. Conclusions Serotonin-like flask-shaped cells such as the ones described herein for Phoronopsis harmeri are found in the majority of lophotrochozoan larvae and therefore most likely belong to the ground pattern of the last common lophotrochozoan ancestor. The finding of a transitory paired ventral neurite bundle with serially repeated commissures that disappears during metamorphosis suggests that such a structure was part of the “ur-phoronid” nervous system, but was lost in the adult stage, probably due to its acquired sessile benthic lifestyle. PMID:22827441

Adolescent toluene inhalation in rats affects white matter maturation with the potential for recovery following abstinence.

PubMed

Duncan, Jhodie Rubina; Dick, Alec Lindsay Ward; Egan, Gary; Kolbe, Scott; Gavrilescu, Maria; Wright, David; Lubman, Dan Ian; Lawrence, Andrew John

2012-01-01

Inhalant misuse is common during adolescence, with ongoing chronic misuse associated with neurobiological and cognitive abnormalities. While human imaging studies consistently report white matter abnormalities among long-term inhalant users, longitudinal studies have been lacking with limited data available regarding the progressive nature of such abnormalities, including the potential for recovery following periods of sustained abstinence. We exposed adolescent male Wistar rats (postnatal day 27) to chronic intermittent inhaled toluene (3,000 ppm) for 1 hour/day, 3 times/week for 8 weeks to model abuse patterns observed in adolescent and young adult human users. This dosing regimen resulted in a significant retardation in weight gain during the exposure period (p<0.05). In parallel, we performed longitudinal magnetic resonance imaging (T₂-weighted) and diffusion tensor imaging prior to exposure, and after 4 and 8 weeks, to examine the integrity of white matter tracts, including the anterior commissure and corpus callosum. We also conducted imaging after 8 weeks of abstinence to assess for potential recovery. Chronic intermittent toluene exposure during adolescence and early adulthood resulted in white matter abnormalities, including a decrease in axial (p<0.05) and radial (p<0.05) diffusivity. These abnormalities appeared region-specific, occurring in the anterior commissure but not the corpus callosum and were not present until after at least 4 weeks of exposure. Toluene-induced effects on both body weight and white matter parameters recovered following abstinence. Behaviourally, we observed a progressive decrease in rearing activity following toluene exposure but no difference in motor function, suggesting cognitive function may be more sensitive to the effects of toluene. Furthermore, deficits in rearing were present by 4 weeks suggesting that toluene may affect behaviour prior to detectable white matter abnormalities. Consequently, exposure to inhalants that contain toluene during adolescence and early adulthood appear to differentially affect white matter maturation and behavioural outcomes, although recovery can occur following abstinence.

The ventral nerve cord in Cephalocarida (Crustacea): new insights into the ground pattern of Tetraconata.

PubMed

Stegner, Martin E J; Brenneis, Georg; Richter, Stefan

2014-03-01

Cephalocarida are Crustacea with many anatomical features that have been interpreted as plesiomorphic with respect to crustaceans or Tetraconata. While the ventral nerve cord (VNC) has been investigated in many other arthropods to address phylogenetic and evolutionary questions, the few studies that exist on the cephalocarid VNC date back 20 years, and data pertaining to neuroactive substances in particular are too sparse for comparison. We reinvestigated the VNC of adult Hutchinsoniella macracantha in detail, combining immunolabeling (tubulin, serotonin, RFamide, histamine) and nuclear stains with confocal laser microscopy, complemented by 3D-reconstructions based on serial semithin sections. The subesophageal ganglion in Cephalocarida comprises three segmental neuromeres (Md, Mx1, Mx2), while a separate ganglion occurs in all thoracic segments and abdominal segments 1-8. Abdominal segments 9 and 10 and the telson are free of ganglia. The maxillar neuromere and the thoracic ganglia correspond closely in their limb innervation pattern, their pattern of mostly four segmental commissures and in displaying up to six individually identified serotonin-like immunoreactive neurons per body side, which exceeds the number found in most other tetraconates. Only two commissures and two serotonin-like immunoreactive neurons per side are present in abdominal ganglia. The stomatogastric nervous system in H. macracantha corresponds to that in other crustaceans and includes, among other structures, a pair of lateral neurite bundles. These innervate the gut as well as various trunk muscles and are, uniquely, linked to the unpaired median neurite bundle. We propose that most features of the cephalocarid ventral nerve cord (VNC) are plesiomorphic with respect to the tetraconate ground pattern. Further, we suggest that this ground pattern includes more serotonin-like neurons than hitherto assumed, and argue that a sister-group relationship between Cephalocarida and Remipedia, as favored by recent molecular analyses, finds no neuroanatomical support. Copyright © 2013 Wiley Periodicals, Inc.

Adolescent Toluene Inhalation in Rats Affects White Matter Maturation with the Potential for Recovery Following Abstinence

PubMed Central

Egan, Gary; Kolbe, Scott; Gavrilescu, Maria; Wright, David; Lubman, Dan Ian; Lawrence, Andrew John

2012-01-01

Inhalant misuse is common during adolescence, with ongoing chronic misuse associated with neurobiological and cognitive abnormalities. While human imaging studies consistently report white matter abnormalities among long-term inhalant users, longitudinal studies have been lacking with limited data available regarding the progressive nature of such abnormalities, including the potential for recovery following periods of sustained abstinence. We exposed adolescent male Wistar rats (postnatal day 27) to chronic intermittent inhaled toluene (3,000 ppm) for 1 hour/day, 3 times/week for 8 weeks to model abuse patterns observed in adolescent and young adult human users. This dosing regimen resulted in a significant retardation in weight gain during the exposure period (p<0.05). In parallel, we performed longitudinal magnetic resonance imaging (T2-weighted) and diffusion tensor imaging prior to exposure, and after 4 and 8 weeks, to examine the integrity of white matter tracts, including the anterior commissure and corpus callosum. We also conducted imaging after 8 weeks of abstinence to assess for potential recovery. Chronic intermittent toluene exposure during adolescence and early adulthood resulted in white matter abnormalities, including a decrease in axial (p<0.05) and radial (p<0.05) diffusivity. These abnormalities appeared region-specific, occurring in the anterior commissure but not the corpus callosum and were not present until after at least 4 weeks of exposure. Toluene-induced effects on both body weight and white matter parameters recovered following abstinence. Behaviourally, we observed a progressive decrease in rearing activity following toluene exposure but no difference in motor function, suggesting cognitive function may be more sensitive to the effects of toluene. Furthermore, deficits in rearing were present by 4 weeks suggesting that toluene may affect behaviour prior to detectable white matter abnormalities. Consequently, exposure to inhalants that contain toluene during adolescence and early adulthood appear to differentially affect white matter maturation and behavioural outcomes, although recovery can occur following abstinence. PMID:23028622

Outcomes of radiofrequency ablation (RFA) and CO2 laser for early glottic cancer.

PubMed

Shuang, Yu; Li, Chao; Zhou, Xuan; Huang, Yongwang; Zhang, Lun

2016-01-01

In the present study, the voice and functional outcomes of radiofrequency ablation (RFA) and CO2 laser for early glottic cancer were evaluated. One hundred sixty eight patients with early glottic cancer from October 2007 to June 2015 were included. Ninety-seven patients underwent RFA and seventy-one patients underwent CO2 laser. The operation time and score of visual analog scale (VAS) for pain on the second day after surgery were recorded. The electronic laryngoscopy was performed at one week, one month and three months of postoperation. The operation time in RFA was shorter than that in CO2 laser (8.52±1.43min vs. 11.76±1.67min, P<0.05). There was no statistical difference in VAS scores between two operation methods (2.86±0.52 vs. 2.89±0.68, P>0.05). One month after operation, the mucosal recovery in RFA group was better than that in CO2 laser group (P<0.05). The alterations of acoustic parameters Jitter, Shimmer and HNR at three time points after operation showed statistical significances in both RFA and CO2 laser groups (P<0.05). The significant differences in acoustic parameters between two groups were also observed (P<0.05). There were no differences in three-year survival rate, local recurrence rate, recurrence rate with anterior commissure involvement and postoperative adhesion rate with anterior commissure between the patients with RFA and CO2 laser (P>0.05). No patient underwent tracheotomy and had symptoms of bucking, dyspnea, severe pain, hemoptysis and other serious complications. Both RFA and CO2 laser are safe and effective for the treatment of early glottic cancer. RFA has the advantage of quick voice recovery, low mucosa injury and short operation time, which is worthy for wide clinical application. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of Clinically Relevant Elliptical Deformations on the Damage Patterns of Sagging and Stretched Leaflets in a Bioprosthetic Heart Valve.

PubMed

Sritharan, Deepa; Fathi, Parinaz; Weaver, Jason D; Retta, Stephen M; Wu, Changfu; Duraiswamy, Nandini

2018-06-12

After implantation of a transcatheter bioprosthetic heart valve its original circular circumference may become distorted, which can lead to changes in leaflet coaptation and leaflets that are stretched or sagging. This may lead to early structural deterioration of the valve as seen in some explanted transcatheter heart valves. Our in vitro study evaluates the effect of leaflet deformations seen in elliptical configurations on the damage patterns of the leaflets, with circular valve deformation as the control. Bovine pericardial tissue heart valves were subjected to accelerated wear testing under both circular (N = 2) and elliptical (N = 4) configurations. The elliptical configurations were created by placing the valve inside custom-made elliptical holders, which caused the leaflets to sag or stretch. The hydrodynamic performance of the valves was monitored and high resolution images were acquired to evaluate leaflet damage patterns over time. In the elliptically deformed valves, sagging leaflets experienced more damage from wear compared to stretched leaflets; the undistorted leaflets of the circular valves experienced the least leaflet damage. Free-edge thinning and tearing were the primary modes of damage in the sagging leaflets. Belly region thinning was seen in the undistorted and stretched leaflets. Leaflet and fabric tears at the commissures were seen in all valve configurations. Free-edge tearing and commissure tears were the leading cause of valve hydrodynamic incompetence. Our study shows that mechanical wear affects heart valve pericardial leaflets differently based on whether they are undistorted, stretched, or sagging in a valve configuration. Sagging leaflets are more likely to be subjected to free-edge tear than stretched or undistorted leaflets. Reducing leaflet stress at the free edge of non-circular valve configurations should be an important factor to consider in the design and/or deployment of transcatheter bioprosthetic heart valves to improve their long-term performance.

Coexpression of high-voltage-activated ion channels Kv3.4 and Cav1.2 in pioneer axons during pathfinding in the developing rat forebrain.

PubMed

Huang, Chia-Yi; Chu, Dachen; Hwang, Wei-Chao; Tsaur, Meei-Ling

2012-11-01

Precise axon pathfinding is crucial for establishment of the initial neuronal network during development. Pioneer axons navigate without the help of preexisting axons and pave the way for follower axons that project later. Voltage-gated ion channels make up the intrinsic electrical activity of pioneer axons and regulate axon pathfinding. To elucidate which channel molecules are present in pioneer axons, immunohistochemical analysis was performed to examine 14 voltage-gated ion channels (Kv1.1-Kv1.3, Kv3.1-Kv3.4, Kv4.3, Cav1.2, Cav1.3, Cav2.2, Nav1.2, Nav1.6, and Nav1.9) in nine axonal tracts in the developing rat forebrain, including the optic nerve, corpus callosum, corticofugal fibers, thalamocortical axons, lateral olfactory tract, hippocamposeptal projection, anterior commissure, hippocampal commissure, and medial longitudinal fasciculus. We found A-type K⁺ channel Kv3.4 in both pioneer axons and early follower axons and L-type Ca²⁺ channel Cav1.2 in pioneer axons and early and late follower axons. Spatially, Kv3.4 and Cav1.2 were colocalized with markers of pioneer neurons and pioneer axons, such as deleted in colorectal cancer (DCC), in most fiber tracts examined. Temporally, Kv3.4 and Cav1.2 were expressed abundantly in most fiber tracts during axon pathfinding but were downregulated beginning in synaptogenesis. By contrast, delayed rectifier Kv channels (e.g., Kv1.1) and Nav channels (e.g., Nav1.2) were absent from these fiber tracts (except for the corpus callosum) during pathfinding of pioneer axons. These data suggest that Kv3.4 and Cav1.2, two high-voltage-activated ion channels, may act together to control Ca²⁺ -dependent electrical activity of pioneer axons and play important roles during axon pathfinding. Copyright © 2012 Wiley Periodicals, Inc.

Synergy as design principle for metabolic engineering of 1-propanol production in Escherichia coli.

PubMed

Shen, Claire R; Liao, James C

2013-05-01

Synthesis of a desired product can often be achieved via more than one metabolic pathway. Whether naturally evolved or synthetically engineered, these pathways often exhibit specific properties that are suitable for production under distinct conditions and host organisms. Synergy between pathways arises when the underlying pathway characteristics, such as reducing equivalent demand, ATP requirement, intermediate utilization, and cofactor preferences, are complementary to each other. Utilization of such pathways in combination leads to an increased metabolite productivity and/or yield compared to using each pathway alone. This work illustrates the principle of synergy between two different pathways for 1-propanol production in Escherichia coli. A model-guided design based on maximum theoretical yield calculations identified synergy of the native threonine pathway and the heterologous citramalate pathway in terms of production yield across all flux ratios between the two pathways. Characterization of the individual pathways by host gene deletions demonstrates their distinct metabolic characteristics: the necessity of TCA cycle for threonine pathway and the independence of TCA cycle for the citramalate pathway. The two pathways are also complementary in driving force demands. Production experiments verified the synergistic effects predicted by the yield model, in which the platform with dual pathway for 2-ketobutyrate synthesis achieved higher yield (0.15g/g of glucose) and productivity (0.12g/L/h) of 1-propanol than individual ones alone: the threonine pathway (0.09g/g; 0.04g/L/h) or the citramalate pathway (0.11g/g; 0.04g/L/h). Thus, incorporation of synergy into the design principle of metabolic engineering may improve the production yield and rate of the desired compound. Copyright © 2013 Elsevier Inc. All rights reserved.

One step DNA assembly for combinatorial metabolic engineering.

PubMed

Coussement, Pieter; Maertens, Jo; Beauprez, Joeri; Van Bellegem, Wouter; De Mey, Marjan

2014-05-01

The rapid and efficient assembly of multi-step metabolic pathways for generating microbial strains with desirable phenotypes is a critical procedure for metabolic engineering, and remains a significant challenge in synthetic biology. Although several DNA assembly methods have been developed and applied for metabolic pathway engineering, many of them are limited by their suitability for combinatorial pathway assembly. The introduction of transcriptional (promoters), translational (ribosome binding site (RBS)) and enzyme (mutant genes) variability to modulate pathway expression levels is essential for generating balanced metabolic pathways and maximizing the productivity of a strain. We report a novel, highly reliable and rapid single strand assembly (SSA) method for pathway engineering. The method was successfully optimized and applied to create constructs containing promoter, RBS and/or mutant enzyme libraries. To demonstrate its efficiency and reliability, the method was applied to fine-tune multi-gene pathways. Two promoter libraries were simultaneously introduced in front of two target genes, enabling orthogonal expression as demonstrated by principal component analysis. This shows that SSA will increase our ability to tune multi-gene pathways at all control levels for the biotechnological production of complex metabolites, achievable through the combinatorial modulation of transcription, translation and enzyme activity. Copyright © 2014 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Jupyter and Galaxy: Easing entry barriers into complex data analyses for biomedical researchers.

PubMed

Grüning, Björn A; Rasche, Eric; Rebolledo-Jaramillo, Boris; Eberhard, Carl; Houwaart, Torsten; Chilton, John; Coraor, Nate; Backofen, Rolf; Taylor, James; Nekrutenko, Anton

2017-05-01

What does it take to convert a heap of sequencing data into a publishable result? First, common tools are employed to reduce primary data (sequencing reads) to a form suitable for further analyses (i.e., the list of variable sites). The subsequent exploratory stage is much more ad hoc and requires the development of custom scripts and pipelines, making it problematic for biomedical researchers. Here, we describe a hybrid platform combining common analysis pathways with the ability to explore data interactively. It aims to fully encompass and simplify the "raw data-to-publication" pathway and make it reproducible.

Molecular profiles to biology and pathways: a systems biology approach.

PubMed

Van Laere, Steven; Dirix, Luc; Vermeulen, Peter

2016-06-16

Interpreting molecular profiles in a biological context requires specialized analysis strategies. Initially, lists of relevant genes were screened to identify enriched concepts associated with pathways or specific molecular processes. However, the shortcoming of interpreting gene lists by using predefined sets of genes has resulted in the development of novel methods that heavily rely on network-based concepts. These algorithms have the advantage that they allow a more holistic view of the signaling properties of the condition under study as well as that they are suitable for integrating different data types like gene expression, gene mutation, and even histological parameters.

Adaptation Pathway of Low Impact Development Planning under Climate Change for a Sustainable Rural Community

NASA Astrophysics Data System (ADS)

Chen, P. Y.; Tung, C. P.

2016-12-01

The study focuses on developing the methodology of adaptation pathway for storm water management in a community scale. Following previous results on adaptation procedures including problem and goal setup, current risk assessment and analysis, future risk assessment and analysis, and adaptation options identification and evaluation, the study aims at analyzing adaptation pathway planning and implementation, namely the fifth step, for applying low impact development (LID). Based on the efficacy analyses of the feasible adaptation options, an adaptation pathway map can be build. Each pathway is a combination of the adaptation measures arranged in certain order. The developed adaptation pathway map visualizes the relative effectiveness and the connection of the adaptation measures. In addition, the tipping points of the system can be clearly identified and the triggers can be defined accordingly. There are multiple choices of pathways in an adaptation pathway map, which can be referred as pathway candidates. To ensure the applicability and operability, the methodology of adaptation pathway analysis is applied to a case study. Required information for developing an adaptation pathway map includes the scores of the adaptation options on the criteria, namely the effects, costs, immediacy, and side effect. Feasible adaptation options for the design case are dredging, pipeline expansion, pumping station, LID and detention pond. By ranking the options according to the criteria, LID is found dominating dredging and pumping station in this case. The information of the pathway candidates can be further used by the stakeholders to select the most suitable and promising pathway.

Road Maps for Learning: A Bird's Eye View

ERIC Educational Resources Information Center

Dunne, Timothy T.

2011-01-01

The notion of the road map, advocated by Black, Wilson, and Yao (2011), and the associated minutiae of the construct map have several powerful features. At one level these notions assist the teacher to select and embody a suitable sequence of constructs within a specified curriculum. Whatever disparate sequenced pathways individual learners may…

In situ hybridization of oxytocin messenger RNA: macroscopic distribution and quantitation in rat hypothalamic cell groups

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burbach, J.P.; Voorhuis, T.A.; van Tol, H.H.

1987-05-29

Oxytocin mRNA was detected in the rat hypothalamus by in situ hybridization to a single stranded /sup 35/S-labelled DNA probe and the distribution of oxytocin mRNA-containing cell groups was studied at the macroscopic level. Specificity of hybridization was confirmed by comparison to vasopressin mRNA hybridization in parallel tissue sections. Cell groups containing oxytocin mRNA were confined to a set of hypothalamic cell groups, i.c. the supraoptic, paraventricular, anterior commissural nuclei, nucleus circularis and scattered hypothalamic islets. These cell groups displayed similar densities of autoradiographic signals indicating that the oxytocin gene is expressed at approximately the same average level at thesemore » various sites.« less

A three-dimensional evaluation of human facial asymmetry.

PubMed Central

Ferrario, V F; Sforza, C; Miani, A; Serrao, G

1995-01-01

Soft-tissue facial asymmetry was studied in a group of 80 young healthy white Caucasian adults (40 men, 40 women) with no craniofacial, dental or mandibular disorders. For each subject, the 3-dimensional coordinates of 16 standardised soft-tissue facial landmarks (trichion, nasion, pronasale, subnasale, B point, pogonion, eye lateral canthi, nasal alae, labial commissures, tragi, gonia) were measured by infrared photogrammetry by an automated instrument. The form of the right and left hemifaces was assessed by calculating all the possible linear distances between pairs of landmarks within side. Side differences were tested by using euclidean distance matrix analysis. The mean faces of both groups were significantly asymmetric, i.e. the 2 sides of face showed significant differences in shape, but no differences in size. PMID:7649806

Multiple pathways of commodity crop expansion in tropical forest landscapes

NASA Astrophysics Data System (ADS)

Meyfroidt, Patrick; Carlson, Kimberly M.; Fagan, Matthew E.; Gutiérrez-Vélez, Victor H.; Macedo, Marcia N.; Curran, Lisa M.; DeFries, Ruth S.; Dyer, George A.; Gibbs, Holly K.; Lambin, Eric F.; Morton, Douglas C.; Robiglio, Valentina

2014-07-01

Commodity crop expansion, for both global and domestic urban markets, follows multiple land change pathways entailing direct and indirect deforestation, and results in various social and environmental impacts. Here we compare six published case studies of rapid commodity crop expansion within forested tropical regions. Across cases, between 1.7% and 89.5% of new commodity cropland was sourced from forestlands. Four main factors controlled pathways of commodity crop expansion: (i) the availability of suitable forestland, which is determined by forest area, agroecological or accessibility constraints, and land use policies, (ii) economic and technical characteristics of agricultural systems, (iii) differences in constraints and strategies between small-scale and large-scale actors, and (iv) variable costs and benefits of forest clearing. When remaining forests were unsuitable for agriculture and/or policies restricted forest encroachment, a larger share of commodity crop expansion occurred by conversion of existing agricultural lands, and land use displacement was smaller. Expansion strategies of large-scale actors emerge from context-specific balances between the search for suitable lands; transaction costs or conflicts associated with expanding into forests or other state-owned lands versus smallholder lands; net benefits of forest clearing; and greater access to infrastructure in already-cleared lands. We propose five hypotheses to be tested in further studies: (i) land availability mediates expansion pathways and the likelihood that land use is displaced to distant, rather than to local places; (ii) use of already-cleared lands is favored when commodity crops require access to infrastructure; (iii) in proportion to total agricultural expansion, large-scale actors generate more clearing of mature forests than smallholders; (iv) property rights and land tenure security influence the actors participating in commodity crop expansion, the form of land use displacement, and livelihood outcomes; (v) intensive commodity crops may fail to spare land when inducing displacement. We conclude that understanding pathways of commodity crop expansion is essential to improve land use governance.

Benchmarking organic micropollutants in wastewater, recycled water and drinking water with in vitro bioassays.

PubMed

Escher, Beate I; Allinson, Mayumi; Altenburger, Rolf; Bain, Peter A; Balaguer, Patrick; Busch, Wibke; Crago, Jordan; Denslow, Nancy D; Dopp, Elke; Hilscherova, Klara; Humpage, Andrew R; Kumar, Anu; Grimaldi, Marina; Jayasinghe, B Sumith; Jarosova, Barbora; Jia, Ai; Makarov, Sergei; Maruya, Keith A; Medvedev, Alex; Mehinto, Alvine C; Mendez, Jamie E; Poulsen, Anita; Prochazka, Erik; Richard, Jessica; Schifferli, Andrea; Schlenk, Daniel; Scholz, Stefan; Shiraishi, Fujio; Snyder, Shane; Su, Guanyong; Tang, Janet Y M; van der Burg, Bart; van der Linden, Sander C; Werner, Inge; Westerheide, Sandy D; Wong, Chris K C; Yang, Min; Yeung, Bonnie H Y; Zhang, Xiaowei; Leusch, Frederic D L

2014-01-01

Thousands of organic micropollutants and their transformation products occur in water. Although often present at low concentrations, individual compounds contribute to mixture effects. Cell-based bioassays that target health-relevant biological endpoints may therefore complement chemical analysis for water quality assessment. The objective of this study was to evaluate cell-based bioassays for their suitability to benchmark water quality and to assess efficacy of water treatment processes. The selected bioassays cover relevant steps in the toxicity pathways including induction of xenobiotic metabolism, specific and reactive modes of toxic action, activation of adaptive stress response pathways and system responses. Twenty laboratories applied 103 unique in vitro bioassays to a common set of 10 water samples collected in Australia, including wastewater treatment plant effluent, two types of recycled water (reverse osmosis and ozonation/activated carbon filtration), stormwater, surface water, and drinking water. Sixty-five bioassays (63%) showed positive results in at least one sample, typically in wastewater treatment plant effluent, and only five (5%) were positive in the control (ultrapure water). Each water type had a characteristic bioanalytical profile with particular groups of toxicity pathways either consistently responsive or not responsive across test systems. The most responsive health-relevant endpoints were related to xenobiotic metabolism (pregnane X and aryl hydrocarbon receptors), hormone-mediated modes of action (mainly related to the estrogen, glucocorticoid, and antiandrogen activities), reactive modes of action (genotoxicity) and adaptive stress response pathway (oxidative stress response). This study has demonstrated that selected cell-based bioassays are suitable to benchmark water quality and it is recommended to use a purpose-tailored panel of bioassays for routine monitoring.

Improved Protein Arrays for Quantitative Systems Analysis of the Dynamics of Signaling Pathway Interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Chin-Rang

Astronauts and workers in nuclear plants who repeatedly exposed to low doses of ionizing radiation (IR, <10 cGy) are likely to incur specific changes in signal transduction and gene expression in various tissues of their body. Remarkable advances in high throughput genomics and proteomics technologies enable researchers to broaden their focus from examining single gene/protein kinetics to better understanding global gene/protein expression profiling and biological pathway analyses, namely Systems Biology. An ultimate goal of systems biology is to develop dynamic mathematical models of interacting biological systems capable of simulating living systems in a computer. This Glue Grant is to complementmore » Dr. Boothman’s existing DOE grant (No. DE-FG02-06ER64186) entitled “The IGF1/IGF-1R-MAPK-Secretory Clusterin (sCLU) Pathway: Mediator of a Low Dose IR-Inducible Bystander Effect” to develop sensitive and quantitative proteomic technology that suitable for low dose radiobiology researches. An improved version of quantitative protein array platform utilizing linear Quantum dot signaling for systematically measuring protein levels and phosphorylation states for systems biology modeling is presented. The signals are amplified by a confocal laser Quantum dot scanner resulting in ~1000-fold more sensitivity than traditional Western blots and show the good linearity that is impossible for the signals of HRP-amplification. Therefore this improved protein array technology is suitable to detect weak responses of low dose radiation. Software is developed to facilitate the quantitative readout of signaling network activities. Kinetics of EGFRvIII mutant signaling was analyzed to quantify cross-talks between EGFR and other signaling pathways.« less

Evaluation of the impact of a clinical pathway on the organization of a multidisciplinary dental sleep clinic.

PubMed

Ten Berge, D M; Braem, M J; Altenburg, A; Dieltjens, M; Van de Heyning, P H; Vanhaecht, K; Vanderveken, O M

2014-05-01

Clinical pathways are used to organize complex care processes by providing structure and standardization. The multidisciplinary approach of oral appliance (OA) therapy for sleep-disordered breathing (SDB) is a complex and dynamic process suitable for such a structured pathway approach. A clinical pathway for patients referred for OA therapy was developed and implemented. The aim of this study was to evaluate the impact of this clinical pathway on the time to delivery of the OA and the organization of the multidisciplinary dental sleep clinic (MDSC). The latter was achieved using the care process self-evaluation tool (CPSET). First, development and implementation of the clinical pathway gave structure and shortened the mean time to delivery by 102 days (240 ± 70 vs. 138 ± 33 days) (Mann-Whitney U: P < 0.001). Second, the CPSET scores were obtained in a cohort of 49 healthcare professionals involved in the pathway. Overall, patient-focused organization received the highest scores (80.5 ± 9.0%), whereas cooperation with primary care received the lowest score (66.7 ± 12.4%). This is the first project on clinical pathways in OA therapy for SDB. The implementation of the pathway in our MDSC has created a significant shortening of the time to delivery. A first evaluation of the clinical pathway using the CPSET scores indicates that all disciplines involved should be thoroughly informed in an ongoing approach.

Genome wide transcriptome profiling reveals differential gene expression in secondary metabolite pathway of Cymbopogon winterianus.

PubMed

Devi, Kamalakshi; Mishra, Surajit K; Sahu, Jagajjit; Panda, Debashis; Modi, Mahendra K; Sen, Priyabrata

2016-02-15

Advances in transcriptome sequencing provide fast, cost-effective and reliable approach to generate large expression datasets especially suitable for non-model species to identify putative genes, key pathway and regulatory mechanism. Citronella (Cymbopogon winterianus) is an aromatic medicinal grass used for anti-tumoral, antibacterial, anti-fungal, antiviral, detoxifying and natural insect repellent properties. Despite of having number of utilities, the genes involved in terpenes biosynthetic pathway is not yet clearly elucidated. The present study is a pioneering attempt to generate an exhaustive molecular information of secondary metabolite pathway and to increase genomic resources in Citronella. Using high-throughput RNA-Seq technology, root and leaf transcriptome was analysed at an unprecedented depth (11.7 Gb). Targeted searches identified majority of the genes associated with metabolic pathway and other natural product pathway viz. antibiotics synthesis along with many novel genes. Terpenoid biosynthesis genes comparative expression results were validated for 15 unigenes by RT-PCR and qRT-PCR. Thus the coverage of these transcriptome is comprehensive enough to discover all known genes of major metabolic pathways. This transcriptome dataset can serve as important public information for gene expression, genomics and function genomics studies in Citronella and shall act as a benchmark for future improvement of the crop.

Cell line with endogenous EGFRvIII expression is a suitable model for research and drug development purposes.

PubMed

Stec, Wojciech J; Rosiak, Kamila; Siejka, Paulina; Peciak, Joanna; Popeda, Marta; Banaszczyk, Mateusz; Pawlowska, Roza; Treda, Cezary; Hulas-Bigoszewska, Krystyna; Piaskowski, Sylwester; Stoczynska-Fidelus, Ewelina; Rieske, Piotr

2016-05-31

Glioblastoma is the most common and malignant brain tumor, characterized by high cellular heterogeneity. About 50% of glioblastomas are positive for EGFR amplification, half of which express accompanying EGFR mutation, encoding truncated and constitutively active receptor termed EGFRvIII. Currently, no cell models suitable for development of EGFRvIII-targeting drugs exist, while the available ones lack the intratumoral heterogeneity or extrachromosomal nature of EGFRvIII.The reports regarding the biology of EGFRvIII expressed in the stable cell lines are often contradictory in observations and conclusions. In the present study, we use DK-MG cell line carrying endogenous non-modified EGFRvIII amplicons and derive a sub-line that is near depleted of amplicons, whilst remaining identical on the chromosomal level. By direct comparison of the two lines, we demonstrate positive effects of EGFRvIII on cell invasiveness and populational growth as a result of elevated cell survival but not proliferation rate. Investigation of the PI3K/Akt indicated no differences between the lines, whilst NFκB pathway was over-active in the line strongly expressing EGFRvIII, finding further supported by the effects of NFκB pathway specific inhibitors. Taken together, these results confirm the important role of EGFRvIII in intrinsic and extrinsic regulation of tumor behavior. Moreover, the proposed models are stable, making them suitable for research purposes as well as drug development process utilizing high throughput approach.

Cell line with endogenous EGFRvIII expression is a suitable model for research and drug development purposes

PubMed Central

Stec, Wojciech J.; Rosiak, Kamila; Siejka, Paulina; Peciak, Joanna; Popeda, Marta; Banaszczyk, Mateusz; Pawlowska, Roza; Treda, Cezary; Hulas-Bigoszewska, Krystyna; Piaskowski, Sylwester; Stoczynska-Fidelus, Ewelina; Rieske, Piotr

2016-01-01

Glioblastoma is the most common and malignant brain tumor, characterized by high cellular heterogeneity. About 50% of glioblastomas are positive for EGFR amplification, half of which express accompanying EGFR mutation, encoding truncated and constitutively active receptor termed EGFRvIII. Currently, no cell models suitable for development of EGFRvIII-targeting drugs exist, while the available ones lack the intratumoral heterogeneity or extrachromosomal nature of EGFRvIII. The reports regarding the biology of EGFRvIII expressed in the stable cell lines are often contradictory in observations and conclusions. In the present study, we use DK-MG cell line carrying endogenous non-modified EGFRvIII amplicons and derive a sub-line that is near depleted of amplicons, whilst remaining identical on the chromosomal level. By direct comparison of the two lines, we demonstrate positive effects of EGFRvIII on cell invasiveness and populational growth as a result of elevated cell survival but not proliferation rate. Investigation of the PI3K/Akt indicated no differences between the lines, whilst NFκB pathway was over-active in the line strongly expressing EGFRvIII, finding further supported by the effects of NFκB pathway specific inhibitors. Taken together, these results confirm the important role of EGFRvIII in intrinsic and extrinsic regulation of tumor behavior. Moreover, the proposed models are stable, making them suitable for research purposes as well as drug development process utilizing high throughput approach. PMID:27004406

Cost unit accounting based on a clinical pathway: a practical tool for DRG implementation.

PubMed

Feyrer, R; Rösch, J; Weyand, M; Kunzmann, U

2005-10-01

Setting up a reliable cost unit accounting system in a hospital is a fundamental necessity for economic survival, given the current general conditions in the healthcare system. Definition of a suitable cost unit is a crucial factor for success. We present here the development and use of a clinical pathway as a cost unit as an alternative to the DRG. Elective coronary artery bypass grafting was selected as an example. Development of the clinical pathway was conducted according to a modular concept that mirrored all the treatment processes across various levels and modules. Using service records and analyses the process algorithms of the clinical pathway were developed and visualized with CorelTM iGrafix Process 2003. A detailed process cost record constituted the basis of the pathway costing, in which financial evaluation of the treatment processes was performed. The result of this study was a structured clinical pathway for coronary artery bypass grafting together with a cost calculation in the form of cost unit accounting. The use of a clinical pathway as a cost unit offers considerable advantages compared to the DRG or clinical case. The variance in the diagnoses and procedures within a pathway is minimal, so the consumption of resources is homogeneous. This leads to a considerable improvement in the value of cost unit accounting as a strategic control instrument in hospitals.

MOEX: Solvent extraction approach for recycling enriched 98Mo/ 100Mo material

DOE PAGES

Tkac, Peter; Brown, M. Alex; Momen, Abdul; ...

2017-03-20

Several promising pathways exist for the production of 99Mo/ 99mTc using enriched 98Mo or 100Mo. Use of Mo targets require a major change in current generator technology, and the necessity for an efficient recycle pathway to recover valuable enriched Mo material. High recovery yields, purity, suitable chemical form and particle size are required. Results on the development of the MOEX– molybdenum solvent extraction – approach to recycle enriched Mo material are presented. Furthermore, the advantages of the MOEX process are very high decontamination factors from potassium and other elements, high throughput, easy scalability, automation, and minimal waste generation.

MOEX: Solvent extraction approach for recycling enriched 98Mo/ 100Mo material

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tkac, Peter; Brown, M. Alex; Momen, Abdul

Several promising pathways exist for the production of 99Mo/ 99mTc using enriched 98Mo or 100Mo. Use of Mo targets require a major change in current generator technology, and the necessity for an efficient recycle pathway to recover valuable enriched Mo material. High recovery yields, purity, suitable chemical form and particle size are required. Results on the development of the MOEX– molybdenum solvent extraction – approach to recycle enriched Mo material are presented. Furthermore, the advantages of the MOEX process are very high decontamination factors from potassium and other elements, high throughput, easy scalability, automation, and minimal waste generation.

Whole genome mRNA transcriptomics analysis reveals different modes of action of the diarrheic shellfish poisons okadaic acid and dinophysis toxin-1 versus azaspiracid-1 in Caco-2 cells.

PubMed

Bodero, Marcia; Hoogenboom, Ron L A P; Bovee, Toine F H; Portier, Liza; de Haan, Laura; Peijnenburg, Ad; Hendriksen, Peter J M

2018-02-01

A study with DNA microarrays was performed to investigate the effects of two diarrhetic and one azaspiracid shellfish poison, okadaic acid (OA), dinophysistoxin-1 (DTX-1) and azaspiracid-1 (AZA-1) respectively, on the whole-genome mRNA expression of undifferentiated intestinal Caco-2 cells. Previously, the most responding genes were used to develop a dedicated array tube test to screen shellfish samples on the presence of these toxins. In the present study the whole genome mRNA expression was analyzed in order to reveal modes of action and obtain hints on potential biomarkers suitable to be used in alternative bioassays. Effects on key genes in the most affected pathways and processes were confirmed by qPCR. OA and DTX-1 induced almost identical effects on mRNA expression, which strongly indicates that OA and DTX-1induce similar toxic effects. Biological interpretation of the microarray data indicates that both compounds induce hypoxia related pathways/processes, the unfolded protein response (UPR) and endoplasmic reticulum (ER) stress. The gene expression profile of AZA-1 is different and shows increased mRNA expression of genes involved in cholesterol synthesis and glycolysis, suggesting a different mode of action for this toxin. Future studies should reveal whether identified pathways provide suitable biomarkers for rapid detection of DSPs in shellfish. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

The reaction pathway of membrane-bound rat liver mitochondrial monoamine oxidase

PubMed Central

Houslay, Miles D.; Tipton, Keith F.

1973-01-01

1. A preparation of a partly purified mitochondrial outer-membrane fraction suitable for kinetic investigations of monoamine oxidase is described. 2. An apparatus suitable for varying the O2 concentration in a spectrophotometer cuvette is described. 3. The reaction catalysed by the membrane-bound enzyme is shown to proceed by a double-displacement (Ping Pong) mechanism, and a formal mechanism is proposed. 4. KCN, NaN3, benzyl cyanide and 4-cyanophenol are shown to be reversible inhibitors of the enzyme. 5. The non-linear reciprocal plot obtained with impure preparations of benzylamine, which is typical of high substrate inhibition, is shown to be due to aldehyde contamination of the substrate. PMID:4778271

Pathway to oxide photovoltaics via band-structure engineering of SnO

DOE PAGES

Peng, Haowei; Bikowski, Andre; Zakutayev, Andriy; ...

2016-10-04

All-oxide photovoltaics could open rapidly scalable manufacturing routes, if only oxide materials with suitable electronic and optical properties were developed. SnO has exceptional doping and transport properties among oxides, but suffers from a strongly indirect band gap. Here, we address this shortcoming by band-structure engineering through isovalent but heterostructural alloying with divalent cations (Mg, Ca, Sr, and Zn). Furthermore, using first-principles calculations, we show that suitable band gaps and optical properties close to that of direct semiconductors are achievable, while the comparatively small effective masses are preserved in the alloys. Initial thin film synthesis and characterization support the feasibility ofmore » the approach.« less

An HTRF® Assay for the Protein Kinase ATM.

PubMed

Adams, Phillip; Clark, Jonathan; Hawdon, Simon; Hill, Jennifer; Plater, Andrew

2017-01-01

Ataxia telangiectasia mutated (ATM) is a serine/threonine kinase that plays a key role in the regulation of DNA damage pathways and checkpoint arrest. In recent years, there has been growing interest in ATM as a therapeutic target due to its association with cancer cell survival following genotoxic stress such as radio- and chemotherapy. Large-scale targeted drug screening campaigns have been hampered, however, by technical issues associated with the production of sufficient quantities of purified ATM and the availability of a suitable high-throughput assay. Using a purified, functionally active recombinant ATM and one of its physiological substrates, p53, we have developed an in vitro FRET-based activity assay that is suitable for high-throughput drug screening.

A telencephalospinal projection in the Tegu lizard (Tupinambis teguixin).

PubMed

Follett, K A

1989-09-04

Tegu lizards (Tupinambis teguixin) were studied to determine the presence of a homologue of the mammalian corticospinal tract. The sources of telencephalic efferent projections to the spinal cord were determined by evaluating the localization of retrogradely transported horseradish peroxidase applied in the cervical spinal cord. Labeled cells were present in subtelencephalic sites reported previously by other authors and, in addition, were found in the principal sensory and motor nuclei of the trigeminal nerve and in the nucleus of the posterior commissure. A telencephalospinal projection was identified, originating in the ventral caudal telencephalon. Histochemical staining revealed a high concentration of acetylcholinesterase in cells and neuropil in the same area. This tract is suggested to be homologous to the mammalian amygdalospinal tract. No reptilian homologue of the corticospinal tract was identified.

A 76-year old man with a torn Freedom SOLO bioprosthesis.

PubMed

Wollersheim, Laurens W; Li, Wilson W; van der Meulen, Jan; de Mol, Bas A

2014-01-01

We describe a case of a 76-year old male who presented with progressive dyspnoea. He underwent an aortic valve replacement with a Freedom SOLO bioprosthesis 6 years ago. Transthoracic echocardiography showed a moderate-to-severe leakage of the Freedom SOLO bioprosthesis. During surgical reintervention, a partial tear of the left coronary cusp was seen from the commissure of the right coronary cusp to its base. After radiographic and microscopic examination, no clear cause was found for the failure of this Freedom SOLO bioprosthesis. To our knowledge, this is the third failure of a Freedom SOLO bioprosthesis reported in the literature. When the long-term follow-up of the Freedom SOLO bioprosthesis is available, it has to be compared with other bioprosthesis for long-term durability.

The role of the Hippo pathway in human disease and tumorigenesis

PubMed Central

2014-01-01

Understanding the molecular nature of human cancer is essential to the development of effective and personalized therapies. Several different molecular signal transduction pathways drive tumorigenesis when deregulated and respond to different types of therapeutic interventions. The Hippo signaling pathway has been demonstrated to play a central role in the regulation of tissue and organ size during development. The deregulation of Hippo signaling leads to a concurrent combination of uncontrolled cellular proliferation and inhibition of apoptosis, two key hallmarks in cancer development. The molecular nature of this pathway was first uncovered in Drosophila melanogaster through genetic screens to identify regulators of cell growth and cell division. The pathway is strongly conserved in humans, rendering Drosophila a suitable and efficient model system to better understand the molecular nature of this pathway. In the present study, we review the current understanding of the molecular mechanism and clinical impact of the Hippo pathway. Current studies have demonstrated that a variety of deregulated molecules can alter Hippo signaling, leading to the constitutive activation of the transcriptional activator YAP or its paralog TAZ. Additionally, the Hippo pathway integrates inputs from a number of growth signaling pathways, positioning the Hippo pathway in a central role in the regulation of tissue size. Importantly, deregulated Hippo signaling is frequently observed in human cancers. YAP is commonly activated in a number of in vitro and in vivo models of tumorigenesis, as well as a number of human cancers. The common activation of YAP in many different tumor types provides an attractive target for potential therapeutic intervention. PMID:25097728

Rapid compensatory changes in GABA receptor efficacy in rat vestibular neurones after unilateral labyrinthectomy

PubMed Central

Yamanaka, Toshiaki; Him, Aydin; Cameron, Susan A; Dutia, Mayank B

2000-01-01

The inhibitory effects of the GABAA agonist muscimol and the GABAB agonist baclofen on tonically active medial vestibular nucleus (MVN) neurones were recorded in slices of the rat dorsal brainstem in vitro, to determine whether any changes occurred in the functional efficacy of GABAergic inhibition in these cells during the initial rapid stage of ‘vestibular compensation’, the behavioural recovery that takes place after unilateral labyrinthectomy (UL). These experiments were carried out in preparations where the midline was cut, severing all commissural connections between the two vestibular nuclei. Slices of the MVN were prepared from normal animals and animals that had been unilaterally labyrinthectomised 4 h earlier. The mean in vitro discharge rate of MVN neurones in the rostral region of the ipsi-lesional nucleus after UL was significantly higher than that in control slices, confirming our earlier reports of an increase in intrinsic excitability of these cells in the early stage of vestibular compensation. The in vitro discharge rates of caudal ipsi-lesional MVN cells, and rostral and caudal contra-lesional MVN cells, were not different from controls. Muscimol and baclofen caused reversible, dose-related inhibition of the tonic discharge rate of MVN cells in control slices. In slices prepared from UL animals, MVN cells in the rostral region of the ipsi-lesional nucleus showed a marked downregulation of their response to both muscimol and baclofen, seen as a rightward shift and a decrease in slope of the dose-response relationships for the two agonists. In the contra-lesional nucleus, there was a small but significant upregulation of the responsiveness of both rostral and caudal MVN cells to baclofen, and a marked upregulation of the responsiveness of caudal MVN cells to muscimol. In slices from animals that had undergone bilateral labyrinthectomy 4 h earlier, the downregulation of the functional efficacy of GABA receptors in the rostral MVN cells did not occur. The changes in GABA receptor efficacy after UL are therefore not due to the vestibular de-afferentation itself, but are instead due to the imbalance in excitability of the vestibular nuclei of the lesioned and intact sides, and the enhanced commissural inhibition of the ipsi-lesional MVN cells that follows UL. The downregulation of GABA receptor efficacy in the ipsi-lesional MVN neurones is functionally compensatory, in that their response to commissural and cerebellar inhibitory drive will be significantly reduced after UL. Their intrinsic membrane conductances, and their remaining excitatory synaptic inputs, will consequently be more effective in causing depolarisation and the restoration of resting activity. Simultaneously the upregulation of GABAergic efficacy in the contra-lesional MVN will tend to reduce the hyperactivity on the contralateral side. These adaptive changes therefore represent a plausible cellular mechanism for the recovery of resting discharge in the ipsi-lesional MVN neurones, and the ‘re-balancing’ of the excitability of the vestibular neurones of the lesioned and intact sides, as occurs after UL in vivo. We propose that the adaptive regulation of the functional efficacy of GABA receptors in the MVN neurones may be an important cellular mechanism for the ‘homeostasis of bilateral excitability’ of the vestibular nuclei of the two sides. PMID:10699085

The Biological Connection Markup Language: a SBGN-compliant format for visualization, filtering and analysis of biological pathways

PubMed Central

Rizzetto, Lisa; Guedez, Damariz Rivero; Donato, Michele; Romualdi, Chiara; Draghici, Sorin; Cavalieri, Duccio

2011-01-01

Motivation: Many models and analysis of signaling pathways have been proposed. However, neither of them takes into account that a biological pathway is not a fixed system, but instead it depends on the organism, tissue and cell type as well as on physiological, pathological and experimental conditions. Results: The Biological Connection Markup Language (BCML) is a format to describe, annotate and visualize pathways. BCML is able to store multiple information, permitting a selective view of the pathway as it exists and/or behave in specific organisms, tissues and cells. Furthermore, BCML can be automatically converted into data formats suitable for analysis and into a fully SBGN-compliant graphical representation, making it an important tool that can be used by both computational biologists and ‘wet lab’ scientists. Availability and implementation: The XML schema and the BCML software suite are freely available under the LGPL for download at http://bcml.dc-atlas.net. They are implemented in Java and supported on MS Windows, Linux and OS X. Contact: duccio.cavalieri@unifi.it; sorin@wayne.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:21653523

Deregulated expression of TANK in glioblastomas triggers pro-tumorigenic ERK1/2 and AKT signaling pathways.

PubMed

Stellzig, J; Chariot, A; Shostak, K; Ismail Göktuna, S; Renner, F; Acker, T; Pagenstecher, A; Schmitz, M L

2013-11-11

Signal transmission by the noncanonical IkappaB kinases (IKKs), TANK-binding kinase 1 (TBK1) and IKKɛ, requires interaction with adapter proteins such as TRAF associated NF-κB activator (TANK). Although increased expression or dysregulation of both kinases has been described for a variety of human cancers, this study shows that deregulated expression of the TANK protein is frequently occurring in glioblastomas (GBMs). The functional relevance of TANK was analyzed in a panel of GBM-derived cell lines and revealed that knockdown of TANK arrests cells in the S-phase and prohibits tumor cell migration. Deregulated TANK expression affects several signaling pathways controlling cell proliferation and the inflammatory response. Interference with stoichiometrically assembled signaling complexes by overexpression or silencing of TANK prevented constitutive interferon-regulatory factor 3 (IRF3) phosphorylation. Knockdown of TANK frequently prevents constitutive activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). TANK-mediated ERK1/2 activation is independent from the canonical MAP kinase or ERK kinase (MEK) 1/2-mediated pathway and utilizes an alternative pathway that uses a TBK1/IKKɛ/Akt signaling axis, thus identifying a novel pathway suitable to block constitutive ERK1/2 activity.

Incorporating Topic Assignment Constraint and Topic Correlation Limitation into Clinical Goal Discovering for Clinical Pathway Mining.

PubMed

Xu, Xiao; Jin, Tao; Wei, Zhijie; Wang, Jianmin

2017-01-01

Clinical pathways are widely used around the world for providing quality medical treatment and controlling healthcare cost. However, the expert-designed clinical pathways can hardly deal with the variances among hospitals and patients. It calls for more dynamic and adaptive process, which is derived from various clinical data. Topic-based clinical pathway mining is an effective approach to discover a concise process model. Through this approach, the latent topics found by latent Dirichlet allocation (LDA) represent the clinical goals. And process mining methods are used to extract the temporal relations between these topics. However, the topic quality is usually not desirable due to the low performance of the LDA in clinical data. In this paper, we incorporate topic assignment constraint and topic correlation limitation into the LDA to enhance the ability of discovering high-quality topics. Two real-world datasets are used to evaluate the proposed method. The results show that the topics discovered by our method are with higher coherence, informativeness, and coverage than the original LDA. These quality topics are suitable to represent the clinical goals. Also, we illustrate that our method is effective in generating a comprehensive topic-based clinical pathway model.

Incorporating Topic Assignment Constraint and Topic Correlation Limitation into Clinical Goal Discovering for Clinical Pathway Mining

PubMed Central

Xu, Xiao; Wei, Zhijie

2017-01-01

Clinical pathways are widely used around the world for providing quality medical treatment and controlling healthcare cost. However, the expert-designed clinical pathways can hardly deal with the variances among hospitals and patients. It calls for more dynamic and adaptive process, which is derived from various clinical data. Topic-based clinical pathway mining is an effective approach to discover a concise process model. Through this approach, the latent topics found by latent Dirichlet allocation (LDA) represent the clinical goals. And process mining methods are used to extract the temporal relations between these topics. However, the topic quality is usually not desirable due to the low performance of the LDA in clinical data. In this paper, we incorporate topic assignment constraint and topic correlation limitation into the LDA to enhance the ability of discovering high-quality topics. Two real-world datasets are used to evaluate the proposed method. The results show that the topics discovered by our method are with higher coherence, informativeness, and coverage than the original LDA. These quality topics are suitable to represent the clinical goals. Also, we illustrate that our method is effective in generating a comprehensive topic-based clinical pathway model. PMID:29065617

Deregulated expression of TANK in glioblastomas triggers pro-tumorigenic ERK1/2 and AKT signaling pathways

PubMed Central

Stellzig, J; Chariot, A; Shostak, K; Ismail Göktuna, S; Renner, F; Acker, T; Pagenstecher, A; Schmitz, M L

2013-01-01

Signal transmission by the noncanonical IkappaB kinases (IKKs), TANK-binding kinase 1 (TBK1) and IKKɛ, requires interaction with adapter proteins such as TRAF associated NF-κB activator (TANK). Although increased expression or dysregulation of both kinases has been described for a variety of human cancers, this study shows that deregulated expression of the TANK protein is frequently occurring in glioblastomas (GBMs). The functional relevance of TANK was analyzed in a panel of GBM-derived cell lines and revealed that knockdown of TANK arrests cells in the S-phase and prohibits tumor cell migration. Deregulated TANK expression affects several signaling pathways controlling cell proliferation and the inflammatory response. Interference with stoichiometrically assembled signaling complexes by overexpression or silencing of TANK prevented constitutive interferon-regulatory factor 3 (IRF3) phosphorylation. Knockdown of TANK frequently prevents constitutive activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). TANK-mediated ERK1/2 activation is independent from the canonical MAP kinase or ERK kinase (MEK) 1/2-mediated pathway and utilizes an alternative pathway that uses a TBK1/IKKɛ/Akt signaling axis, thus identifying a novel pathway suitable to block constitutive ERK1/2 activity. PMID:24217713

Design and validation of a critical pathway for hospital management of patients with severe traumatic brain injury.

PubMed

Espinosa-Aguilar, Amilcar; Reyes-Morales, Hortensia; Huerta-Posada, Carlos E; de León, Itzcoatl Limón-Pérez; López-López, Fernando; Mejía-Hernández, Margarita; Mondragón-Martínez, María A; Calderón-Téllez, Ligia M; Amezcua-Cuevas, Rosa L; Rebollar-González, Jorge A

2008-05-01

Critical pathways for the management of patients with severe traumatic brain injury (STBI) may contribute to reducing the incidence of hospital complications, length of hospitalization stay, and cost of care. Such pathways have previously been developed for departments with significant resource availability. In Mexico, STBI is the most important cause of complications and length of stay in neurotrauma services at public hospitals. Although current treatment is designed basically in accordance with the Brain Trauma Foundation guidelines, shortfalls in the availability of local resources make it difficult to comply with these standards, and no critical pathway is available that accords with the resources of public hospitals. The purpose of the present study was to design and to validate a critical pathway for managing STBI patients that would be suitable for implementation in neurotrauma departments of middle-income level countries. The study comprised two phases: design (through literature review and design plan) and validation (content, construct, and appearance) of the critical pathway. The validated critical pathway for managing STBI patients entails four sequential subprocesses summarizing the hospital's care procedures, and includes three components: (1) nodes and criteria (in some cases, indicators are also included); (2) health team members in charge of the patient; (3) maximum estimated time for compliance with recommendations. This validated critical pathway is based on the current scientific evidence and accords with the availability of resources of middle-income countries.

Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities.

PubMed

Menzies, Fiona M; Fleming, Angeleen; Caricasole, Andrea; Bento, Carla F; Andrews, Stephen P; Ashkenazi, Avraham; Füllgrabe, Jens; Jackson, Anne; Jimenez Sanchez, Maria; Karabiyik, Cansu; Licitra, Floriana; Lopez Ramirez, Ana; Pavel, Mariana; Puri, Claudia; Renna, Maurizio; Ricketts, Thomas; Schlotawa, Lars; Vicinanza, Mariella; Won, Hyeran; Zhu, Ye; Skidmore, John; Rubinsztein, David C

2017-03-08

Autophagy is a conserved pathway that delivers cytoplasmic contents to the lysosome for degradation. Here we consider its roles in neuronal health and disease. We review evidence from mouse knockout studies demonstrating the normal functions of autophagy as a protective factor against neurodegeneration associated with intracytoplasmic aggregate-prone protein accumulation as well as other roles, including in neuronal stem cell differentiation. We then describe how autophagy may be affected in a range of neurodegenerative diseases. Finally, we describe how autophagy upregulation may be a therapeutic strategy in a wide range of neurodegenerative conditions and consider possible pathways and druggable targets that may be suitable for this objective. Copyright © 2017 Elsevier Inc. All rights reserved.

Renilla Luciferase-LC3 Based Reporter Assay for Measuring Autophagic Flux.

PubMed

Farkas, T; Jäättelä, M

2017-01-01

Macroautophagy (autophagy) is a dynamic intracellular degradation pathway. Monitoring the flux through the autophagy pathway is experimentally challenging but obviously a prerequisite for the proper investigation of the process. Here, we present an indirect autophagy flux assay based on monitoring the degradation of an autophagosome-associated fusion protein Rluc-LC3 by luminescence detection. The method is suitable for screening purposes with a high number of parallel samples and can be used for measurements in cell lysates as well as in living cells. The Rluc-LC3 assay has proven useful for the identification of genes, miRNAs, and small molecules that regulate autophagy flux in mammalian cells. © 2017 Elsevier Inc. All rights reserved.

Groundwater Pathway Model for the Los Alamos National Laboratory Technical Area 21, Material Disposal Area T

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stauffer, Philip H.; Levitt, Daniel G.; Miller, Terry Ann

2017-02-09

This report consists of four major sections, including this introductory section. Section 2 provides an overview of previous investigations related to the development of the current sitescale model. The methods and data used to develop the 3-D groundwater model and the techniques used to distill that model into a form suitable for use in the GoldSim models are discussed in Section 3. Section 4 presents the results of the model development effort and discusses some of the uncertainties involved. Three attachments that provide details about the components and data used in this groundwater pathway model are also included with thismore » report.« less

Populations of subplate and interstitial neurons in fetal and adult human telencephalon.

PubMed

Judaš, Miloš; Sedmak, Goran; Pletikos, Mihovil; Jovanov-Milošević, Nataša

2010-10-01

In the adult human telencephalon, subcortical (gyral) white matter contains a special population of interstitial neurons considered to be surviving descendants of fetal subplate neurons [Kostovic & Rakic (1980) Cytology and the time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J Neurocytol9, 219]. We designate this population of cells as superficial (gyral) interstitial neurons and describe their morphology and distribution in the postnatal and adult human cerebrum. Human fetal subplate neurons cannot be regarded as interstitial, because the subplate zone is an essential part of the fetal cortex, the major site of synaptogenesis and the 'waiting' compartment for growing cortical afferents, and contains both projection neurons and interneurons with distinct input-output connectivity. However, although the subplate zone is a transient fetal structure, many subplate neurons survive postnatally as superficial (gyral) interstitial neurons. The fetal white matter is represented by the intermediate zone and well-defined deep periventricular tracts of growing axons, such as the corpus callosum, anterior commissure, internal and external capsule, and the fountainhead of the corona radiata. These tracts gradually occupy the territory of transient fetal subventricular and ventricular zones.The human fetal white matter also contains distinct populations of deep fetal interstitial neurons, which, by virtue of their location, morphology, molecular phenotypes and advanced level of dendritic maturation, remain distinct from subplate neurons and neurons in adjacent structures (e.g. basal ganglia, basal forebrain). We describe the morphological, histochemical (nicotinamide-adenine dinucleotide phosphate-diaphorase) and immunocytochemical (neuron-specific nuclear protein, microtubule-associated protein-2, calbindin, calretinin, neuropeptide Y) features of both deep fetal interstitial neurons and deep (periventricular) interstitial neurons in the postnatal and adult deep cerebral white matter (i.e. corpus callosum, anterior commissure, internal and external capsule and the corona radiata/centrum semiovale). Although these deep interstitial neurons are poorly developed or absent in the brains of rodents, they represent a prominent feature of the significantly enlarged white matter of human and non-human primate brains. © 2010 The Authors. Journal of Anatomy © 2010 Anatomical Society of Great Britain and Ireland.

Selective neuronal staining in tardigrades and onychophorans provides insights into the evolution of segmental ganglia in panarthropods

PubMed Central

2013-01-01

Background Although molecular analyses have contributed to a better resolution of the animal tree of life, the phylogenetic position of tardigrades (water bears) is still controversial, as they have been united alternatively with nematodes, arthropods, onychophorans (velvet worms), or onychophorans plus arthropods. Depending on the hypothesis favoured, segmental ganglia in tardigrades and arthropods might either have evolved independently, or they might well be homologous, suggesting that they were either lost in onychophorans or are a synapomorphy of tardigrades and arthropods. To evaluate these alternatives, we analysed the organisation of the nervous system in three tardigrade species using antisera directed against tyrosinated and acetylated tubulin, the amine transmitter serotonin, and the invertebrate neuropeptides FMRFamide, allatostatin and perisulfakinin. In addition, we performed retrograde staining of nerves in the onychophoran Euperipatoides rowelli in order to compare the serial locations of motor neurons within the nervous system relative to the appendages they serve in arthropods, tardigrades and onychophorans. Results Contrary to a previous report from a Macrobiotus species, our immunocytochemical and electron microscopic data revealed contralateral fibres and bundles of neurites in each trunk ganglion of three tardigrade species, including Macrobiotus cf. harmsworthi, Paramacrobiotus richtersi and Hypsibius dujardini. Moreover, we identified additional, extra-ganglionic commissures in the interpedal regions bridging the paired longitudinal connectives. Within the ganglia we found serially repeated sets of serotonin- and RFamid-like immunoreactive neurons. Furthermore, our data show that the trunk ganglia of tardigrades, which include the somata of motor neurons, are shifted anteriorly with respect to each corresponding leg pair, whereas no such shift is evident in the arrangement of motor neurons in the onychophoran nerve cords. Conclusions Taken together, these data reveal three major correspondences between the segmental ganglia of tardigrades and arthropods, including (i) contralateral projections and commissures in each ganglion, (ii) segmentally repeated sets of immunoreactive neurons, and (iii) an anteriorly shifted (parasegmental) position of ganglia. These correspondences support the homology of segmental ganglia in tardigrades and arthropods, suggesting that these structures were either lost in Onychophora or, alternatively, evolved in the tardigrade/arthropod lineage. PMID:24152256

Selective neuronal staining in tardigrades and onychophorans provides insights into the evolution of segmental ganglia in panarthropods.

PubMed

Mayer, Georg; Martin, Christine; Rüdiger, Jan; Kauschke, Susann; Stevenson, Paul A; Poprawa, Izabela; Hohberg, Karin; Schill, Ralph O; Pflüger, Hans-Joachim; Schlegel, Martin

2013-10-24

Although molecular analyses have contributed to a better resolution of the animal tree of life, the phylogenetic position of tardigrades (water bears) is still controversial, as they have been united alternatively with nematodes, arthropods, onychophorans (velvet worms), or onychophorans plus arthropods. Depending on the hypothesis favoured, segmental ganglia in tardigrades and arthropods might either have evolved independently, or they might well be homologous, suggesting that they were either lost in onychophorans or are a synapomorphy of tardigrades and arthropods. To evaluate these alternatives, we analysed the organisation of the nervous system in three tardigrade species using antisera directed against tyrosinated and acetylated tubulin, the amine transmitter serotonin, and the invertebrate neuropeptides FMRFamide, allatostatin and perisulfakinin. In addition, we performed retrograde staining of nerves in the onychophoran Euperipatoides rowelli in order to compare the serial locations of motor neurons within the nervous system relative to the appendages they serve in arthropods, tardigrades and onychophorans. Contrary to a previous report from a Macrobiotus species, our immunocytochemical and electron microscopic data revealed contralateral fibres and bundles of neurites in each trunk ganglion of three tardigrade species, including Macrobiotus cf. harmsworthi, Paramacrobiotus richtersi and Hypsibius dujardini. Moreover, we identified additional, extra-ganglionic commissures in the interpedal regions bridging the paired longitudinal connectives. Within the ganglia we found serially repeated sets of serotonin- and RFamid-like immunoreactive neurons. Furthermore, our data show that the trunk ganglia of tardigrades, which include the somata of motor neurons, are shifted anteriorly with respect to each corresponding leg pair, whereas no such shift is evident in the arrangement of motor neurons in the onychophoran nerve cords. Taken together, these data reveal three major correspondences between the segmental ganglia of tardigrades and arthropods, including (i) contralateral projections and commissures in each ganglion, (ii) segmentally repeated sets of immunoreactive neurons, and (iii) an anteriorly shifted (parasegmental) position of ganglia. These correspondences support the homology of segmental ganglia in tardigrades and arthropods, suggesting that these structures were either lost in Onychophora or, alternatively, evolved in the tardigrade/arthropod lineage.

Study of the Histopathologic Characteristics and Surface Morphologies of Glottic Carcinomas With Anterior Vocal Commissure Involvement.

PubMed

Wu, Jianhui; Zhao, Jing; Wang, Zhangfeng; Li, Zenghong; Luo, Jie; Liao, Bing; Yang, Zhiyun; Liu, Qihong; Wang, Bin; Wen, Weiping; Lei, Wenbin

2015-07-01

This article explores the features and the role of the anterior vocal commissure (AVC) structure and the surface morphologies of glottic carcinomas with AVC involvement to provide a reference for the selection of transoral carbon dioxide (CO2) laser surgery. A total of 31 cases of glottic carcinomas with AVC involvement from May 2012 to January 2014 were included. All patients underwent electronic laryngoscopic examinations and computed tomography scans to determine the surface morphology. After surgery, the tumor specimens were resected integrally, and axial serial sections parallel to the plane of vocal cords were taken to explore the features and possible invasion paths of the glottic carcinomas with AVC involvement. The rates of involvement of the supraglottis and subglottis were 71.4% and 14.8%, respectively, via the AVC. The involvement of the superficial layer of the unilateral or bilateral vocal cords without involvement of the vocal muscle in the AVC region (IVM) or the cartilage was present in 15 cases (48.4%). The involvement of the superficial layer of the unilateral and bilateral vocal cords occurred in 16 cases (51.6%) with the IVM in 13 cases and the involvement of the intermediate lamina of the thyroid cartilage (ITC) in 8 cases. The involvement of the ITC was associated with the involvement of the vocal muscle of the AVC region (P < 0.05). Among the pushing carcinomas, 15 of 21 (71.4%) presented with well-defined tumor mass, and 8 of 10 (80.0%) infiltrating carcinomas presented with multiple tumor nests that were often surrounded by fibrosis (P < 0.05). The AVC is an important path of invasion of subglottic in glottic carcinomas but less so for suparglottic. The Broyles' ligaments acted as a barrier against the spread of the tumors to the thyroid cartilage, but this role was obviously weaken by the involvement of the vocal muscle of the AVC region. The infiltrating carcinomas presented with multiple tumor nests in fibrous tissue. When CO2 laser microsurgery is considered as a treatment option, these facts should be kept in mind.

The role of diffusion tensor imaging tractography for Gamma Knife thalamotomy planning.

PubMed

Gomes, João Gabriel Ribeiro; Gorgulho, Alessandra Augusta; de Oliveira López, Amanda; Saraiva, Crystian Wilian Chagas; Damiani, Lucas Petri; Pássaro, Anderson Martins; Salvajoli, João Victor; de Oliveira Siqueira, Ludmila; Salvajoli, Bernardo Peres; De Salles, Antônio Afonso Ferreira

2016-12-01

OBJECTIVE The role of tractography in Gamma Knife thalamotomy (GK-T) planning is still unclear. Pyramidal tractography might reduce the risk of radiation injury to the pyramidal tract and reduce motor complications. METHODS In this study, the ventralis intermedius nucleus (VIM) targets of 20 patients were bilaterally defined using Iplannet Stereotaxy Software, according to the anterior commissure-posterior commissure (AC-PC) line and considering the localization of the pyramidal tract. The 40 targets and tractography were transferred as objects to the GammaPlan Treatment Planning System (GP-TPS). New targets were defined, according to the AC-PC line in the functional targets section of the GP-TPS. The target offsets required to maintain the internal capsule (IC) constraint of < 15 Gy were evaluated. In addition, the strategies available in GP-TPS to maintain the minimum conventional VIM target dose at > 100 Gy were determined. RESULTS A difference was observed between the positions of both targets and the doses to the IC. The lateral (x) and the vertical (z) coordinates were adjusted 1.9 mm medially and 1.3 mm cranially, respectively. The targets defined considering the position of the pyramidal tract were more medial and superior, based on the constraint of 15 Gy touching the object representing the IC in the GP-TPS. The best strategy to meet the set constraints was 90° Gamma angle (GA) with automatic shaping of dose distribution; this was followed by 110° GA. The worst GA was 70°. Treatment time was substantially increased by the shaping strategy, approximately doubling delivery time. CONCLUSIONS Routine use of DTI pyramidal tractography might be important to fine-tune GK-T planning. DTI tractography, as well as anisotropy showing the VIM, promises to improve Gamma Knife functional procedures. They allow for a more objective definition of dose constraints to the IC and targeting. DTI pyramidal tractography introduced into the treatment planning may reduce the incidence of motor complications and improve efficacy. This needs to be validated in a large clinical series.

Functional correlates of central white matter maturation in perinatal period in rabbits.

PubMed

Drobyshevsky, Alexander; Jiang, Rugang; Derrick, Matthew; Luo, Kehuan; Tan, Sidhartha

2014-11-01

Anisotropy indices derived from diffusion tensor imaging (DTI) are being increasingly used as biomarkers of central WM structural maturation, myelination and even functional development. Our hypothesis was that the rate of functional changes in central WM tracts directly reflects rate of changes in structural development as determined by DTI indices. We examined structural and functional development of four major central WM tracts with different maturational trajectories, including internal capsule (IC), corpus callosum (CC), fimbria hippocampi (FH) and anterior commissure (AC). Rabbits were chosen due to perinatal brain development being similar to humans, and four time points were studied: P1, P11, P18 and adults. Imaging parameters of structural maturation included fractional anisotropy (FA), mean and directional diffusivities derived from DTI, and T2 relaxation time. Axonal composition and degree of myelination were confirmed on electron microscopy. To assess functional maturation, conduction velocity was measured in myelinated and non-myelinated fibers by electrophysiological recordings of compound action potential in perfused brain slices. Diffusion indices and T2 relaxation time in rabbits followed a sigmoid curve during development similar to that for humans, with active changes even at premyelination stage. The shape of the developmental curve was different between the fiber tracts, with later onset but steeper rapid phase of development in IC and FH than in CC. The structural development was not directly related to myelination or to functional development. Functional properties in projection (IC) and limbic tracts (FH) matured earlier than in associative and commissural tracts (CC and AC). The rapid phase of changes in diffusion anisotropy and T2 relaxation time coincided with the development of functional responses and myelination in IC and FH between the second and third weeks of postnatal development in rabbits. In these two tracts, MRI indices could serve as surrogate markers of the early stage of myelination. However, the discordance between developmental change of diffusion indices, myelination and functional properties in CC and AC cautions against equating DTI index changes as biomarkers for myelination in all tracts. Copyright © 2014 Elsevier Inc. All rights reserved.

Gd-based Contrast Enhancement of the Perivascular Spaces in the Basal Ganglia.

PubMed

Naganawa, Shinji; Nakane, Toshiki; Kawai, Hisashi; Taoka, Toshiaki

2017-01-10

In textbooks, the perivascular space (PVS) is described as non-enhancing after the intravenous administration of gadolinium-based contrast agent (IV-GBCA). We noticed that the PVS sometimes has high signal intensity (SI) on heavily T 2 -weighted 3D-FLAIR (hT 2 -FL) images obtained 4 h after IV-GBCA. The purpose of this study was to retrospectively evaluate the contrast enhancement of the PVS. In 8 healthy subjects and 19 patients with suspected endolymphatic hydrops, magnetic resonance cisternography (MRC) and hT 2 -FL images were obtained before and 4 h after a single dose of IV-GBCA. No subjects had renal insufficiency. On axial MRC at the level of the anterior commissure (AC)-posterior commissure (PC) line, 1 cm circular regions of interest (ROIs) were drawn centering on the PVS in the bilateral basal ganglia and thalami. Three-millimeter diameter ROIs were set in the cerebrospinal fluid (CSF) of the bilateral ambient cistern. The ROIs on MRC were copied onto the hT 2 -FL images and the SI was measured. The SI ratio (SIR) was defined as SIR PVS = SI of PVS/SI of the thalami, and SIR CSF = SI of CSF/SI of the thalami. The average of the bilateral values was used for the calculation. The SIR CSF , SIR PVS , and SI of the thalami were compared between before and 4 h after IV-GBCA. The SIR was increased significantly from 1.02 ± 0.37 to 2.65 ± 0.82 in the CSF (P < 0.01) and from 1.20 ± 0.35 to 2.13 ± 1.23 in the PVS at 4 h after IV-GBCA (P < 0.01). The SI of the thalami showed no significant difference. The enhancement of the PVS at 4 h after IV-GBCA was confirmed even in subjects without renal insufficiency. It is possible that the GBCA in the blood vessels might have permeated into the cerebrospinal fluid (CSF) space and the PVS. This might be a first step in the imaging evaluation of the glymphatic system (waste clearance system) of the brain.

Gd-based Contrast Enhancement of the Perivascular Spaces in the Basal Ganglia

PubMed Central

Naganawa, Shinji; Nakane, Toshiki; Kawai, Hisashi; Taoka, Toshiaki

2017-01-01

Purpose: In textbooks, the perivascular space (PVS) is described as non-enhancing after the intravenous administration of gadolinium-based contrast agent (IV-GBCA). We noticed that the PVS sometimes has high signal intensity (SI) on heavily T2-weighted 3D-FLAIR (hT2-FL) images obtained 4 h after IV-GBCA. The purpose of this study was to retrospectively evaluate the contrast enhancement of the PVS. Materials and Methods: In 8 healthy subjects and 19 patients with suspected endolymphatic hydrops, magnetic resonance cisternography (MRC) and hT2-FL images were obtained before and 4 h after a single dose of IV-GBCA. No subjects had renal insufficiency. On axial MRC at the level of the anterior commissure (AC)-posterior commissure (PC) line, 1 cm circular regions of interest (ROIs) were drawn centering on the PVS in the bilateral basal ganglia and thalami. Three-millimeter diameter ROIs were set in the cerebrospinal fluid (CSF) of the bilateral ambient cistern. The ROIs on MRC were copied onto the hT2-FL images and the SI was measured. The SI ratio (SIR) was defined as SIRPVS = SI of PVS/SI of the thalami, and SIRCSF = SI of CSF/SI of the thalami. The average of the bilateral values was used for the calculation. The SIRCSF, SIRPVS, and SI of the thalami were compared between before and 4 h after IV-GBCA. Results: The SIR was increased significantly from 1.02 ± 0.37 to 2.65 ± 0.82 in the CSF (P < 0.01) and from 1.20 ± 0.35 to 2.13 ± 1.23 in the PVS at 4 h after IV-GBCA (P < 0.01). The SI of the thalami showed no significant difference. Conclusion: The enhancement of the PVS at 4 h after IV-GBCA was confirmed even in subjects without renal insufficiency. It is possible that the GBCA in the blood vessels might have permeated into the cerebrospinal fluid (CSF) space and the PVS. This might be a first step in the imaging evaluation of the glymphatic system (waste clearance system) of the brain. PMID:27430361

Study of the Histopathologic Characteristics and Surface Morphologies of Glottic Carcinomas With Anterior Vocal Commissure Involvement

PubMed Central

Wu, Jianhui; Zhao, Jing; Wang, Zhangfeng; Li, Zenghong; Luo, Jie; Liao, Bing; Yang, Zhiyun; Liu, Qihong; Wang, Bin; Wen, Weiping; Lei, Wenbin

2015-01-01

Abstract This article explores the features and the role of the anterior vocal commissure (AVC) structure and the surface morphologies of glottic carcinomas with AVC involvement to provide a reference for the selection of transoral carbon dioxide (CO2) laser surgery. A total of 31 cases of glottic carcinomas with AVC involvement from May 2012 to January 2014 were included. All patients underwent electronic laryngoscopic examinations and computed tomography scans to determine the surface morphology. After surgery, the tumor specimens were resected integrally, and axial serial sections parallel to the plane of vocal cords were taken to explore the features and possible invasion paths of the glottic carcinomas with AVC involvement. The rates of involvement of the supraglottis and subglottis were 71.4% and 14.8%, respectively, via the AVC. The involvement of the superficial layer of the unilateral or bilateral vocal cords without involvement of the vocal muscle in the AVC region (IVM) or the cartilage was present in 15 cases (48.4%). The involvement of the superficial layer of the unilateral and bilateral vocal cords occurred in 16 cases (51.6%) with the IVM in 13 cases and the involvement of the intermediate lamina of the thyroid cartilage (ITC) in 8 cases. The involvement of the ITC was associated with the involvement of the vocal muscle of the AVC region (P < 0.05). Among the pushing carcinomas, 15 of 21 (71.4%) presented with well-defined tumor mass, and 8 of 10 (80.0%) infiltrating carcinomas presented with multiple tumor nests that were often surrounded by fibrosis (P < 0.05). The AVC is an important path of invasion of subglottic in glottic carcinomas but less so for suparglottic. The Broyles’ ligaments acted as a barrier against the spread of the tumors to the thyroid cartilage, but this role was obviously weaken by the involvement of the vocal muscle of the AVC region. The infiltrating carcinomas presented with multiple tumor nests in fibrous tissue. When CO2 laser microsurgery is considered as a treatment option, these facts should be kept in mind. PMID:26200618

Feasibility of a physical activity pathway for Irish primary care physiotherapy services.

PubMed

Barrett, Emer M; Hussey, Juliette; Darker, Catherine D

2017-03-01

To establish consensus on a physical activity pathway suitable for use by physiotherapists in Irish primary care. The physical activity pathway "Let's Get Moving" was examined to agree recruitment criteria and seek consensus on component parts. Modified Delphi approach which attempts to achieve a convergence of opinion, over a series of iterations. Three rounds of questionnaires were used. Primary care. 41 senior physiotherapists working in primary care for a median of 6 years (IQR 3.7 to 8.5). Statements achieving consensus; defined as at least 70% of participants scoring a 6 or a 7, indicating high agreement, on a 7 point Likert scale. The response rate was 98%. There was a high degree of consensus for many components of the pathway. Participants agreed that all patients attending physiotherapy should be eligible for recruitment onto the pathway as well as accepting referrals from other health professionals and direct access from the public. Private physiotherapists highlighted concerns about recruiting fee paying patients onto the pathway. The pathway should be integrated into other preventative and chronic disease programmes in primary care. Modifications to the original pathway included the use of a pedometer in addition to the General Practice Physical Activity Questionnaire. Training needs in physical activity screening and motivational interviewing, as well as additional staffing were identified to support implementation. The Physical Activity Pathway "Let's Get Moving" was accepted as a clinically feasible resource to primary care physiotherapists with some modifications and with the support of additional resources. Copyright © 2016 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Evaluating water management scenarios to support habitat management for the Cape Sable seaside sparrow

USGS Publications Warehouse

Beerens, James M.; Romañach, Stephanie S.; McKelvy, Mark

2016-06-22

The endangered Cape Sable seaside sparrow (Ammodramus maritimus mirabilis) is endemic to south Florida and a key indicator species of marl prairie, a highly diverse freshwater community in the Florida Everglades. Maintenance and creation of suitable habitat is seen as the most important pathway to the persistence of the six existing sparrow subpopulations; however, major uncertainties remain in how to increase suitable habitat within and surrounding these subpopulations, which are vulnerable to environmental stochasticity. Currently, consistently suitable conditions for the Cape Sable seaside sparrow are only present in two of these subpopulations (B and E). The water management scenarios evaluated herein were intended to lower water levels and improve habitat conditions in subpopulation A and D, raise water levels to improve habitat conditions in subpopulations C and F, and minimize impacts to subpopulations B and E. Our objective in this analysis was to compare these scenarios utilizing a set of metrics (short- to long-time scales) that relate habitat suitability to hydrologic conditions. Although hydrologic outputs are similar across scenarios in subpopulation A, scenario R2H reaches the hydroperiod and depth suitability targets more than the other scenarios relative to ECB, while minimizing negative consequences to subpopulation E. However, although R2H hydroperiods are longer than those for ECB during the wet season in subpopulations C and F, depths during the breeding season are predicted to decrease in suitability (less than -50 cm) relative to existing conditions.

Functional Expression of an Orchid Fragrance Gene in Lactococcus lactis

PubMed Central

Song, Adelene Ai Lian; Abdullah, Janna O.; Abdullah, Mohd Puad; Shafee, Norazizah; Rahim, Raha A.

2012-01-01

Vanda Mimi Palmer (VMP), an orchid hybrid of Vanda tesselata and Vanda Tan Chay Yan is a highly scented tropical orchid which blooms all year round. Previous studies revealed that VMP produces a variety of isoprenoid volatiles during daylight. Isoprenoids are well known to contribute significantly to the scent of most fragrant plants. They are a large group of secondary metabolites which may possess valuable characteristics such as flavor, fragrance and toxicity and are produced via two pathways, the mevalonate (MVA) pathway or/and the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway. In this study, a sesquiterpene synthase gene denoted VMPSTS, previously isolated from a floral cDNA library of VMP was cloned and expressed in Lactococcus lactis to characterize the functionality of the protein. L. lactis, a food grade bacterium which utilizes the mevalonate pathway for isoprenoid production was found to be a suitable host for the characterization of plant terpene synthases. Through recombinant expression of VMPSTS, it was revealed that VMPSTS produced multiple sesquiterpenes and germacrene D dominates its profile. PMID:22408409

The endogenous transposable element Tgm9 is suitable for functional analyses of soybean genes and generating novel mutants for genetic improvement of soybean

USDA-ARS?s Scientific Manuscript database

In soybean, variegated flowers can be caused by somatic excision of the CACTA-type transposable element Tgm9 from intron 2 of the DFR2 gene encoding dihydroflavonol-4-reductase in the anthocyanin pigment biosynthetic pathway. DFR2 has been mapped to the W4 locus where the allele containing the elem...

Hole-Accepting-Ligand-Modified CdSe QDs for Dramatic Enhancement of Photocatalytic and Photoelectrochemical Hydrogen Evolution by Solar Energy.

PubMed

Li, Xu-Bing; Liu, Bin; Wen, Min; Gao, Yu-Ji; Wu, Hao-Lin; Huang, Mao-Yong; Li, Zhi-Jun; Chen, Bin; Tung, Chen-Ho; Wu, Li-Zhu

2016-04-01

Solar H 2 evolution of CdSe QDs can be significantly enhanced simply by introducing a suitable hole-accepting-ligand for achieving efficient hole extraction and transfer at the nanoscale interfaces, which opens an effective pathway for dissociation of excitons to generate long-lived charge separation, thus improving the solar-to-fuel conversion efficiency.

Bacterial transformation of terpenoids

NASA Astrophysics Data System (ADS)

Grishko, V. V.; Nogovitsina, Y. M.; Ivshina, I. B.

2014-04-01

Data on the bacterial transformation of terpenoids published in the literature in the past decade are analyzed. Possible pathways for chemo-, regio- and stereoselective modifications of terpenoids are discussed. Considerable attention is given to new technological approaches to the synthesis of terpenoid derivatives suitable for the use in the perfume and food industry and promising as drugs and chiral intermediates for fine organic synthesis. The bibliography includes 246 references.

Technoeconomic and policy drivers of project performance for bioenergy alternatives using biomass from beetle-killed trees

Treesearch

Robert M. Campbell; Nathaniel M. Anderson; Daren E. Daugaard; Helen T. Naughton

2018-01-01

As a result of widespread mortality from beetle infestation in the forests of the western United States, there are substantial stocks of biomass suitable as a feedstock for energy production. This study explored the financial viability of four production pathway scenarios for the conversion of beetle-killed pine to bioenergy and bioproducts in the Rocky Mountains....

Galea and subgalea graft for lip augmentation revision.

PubMed

de Benito, J; Fernández-Sanza, I

1996-01-01

In this paper we will review the results obtained during the last 2 years with the aponeurotic galea and subgalea for vermillion lip augmentation. The survey was carried out on 42 patients who displayed either an absence of or reduction in the vermillion of one or both lips or a senile lip. In all cases the surgical procedure introduced aponeurotic galea and subgalea in the space found between the orbicular lip muscle and the vestibular mucus, just behind the vermillion. All the operations were performed under local anaesthetic. The size of the aponeurotic galea fragment removed varied in length between 10 and 12 cms. and in width between 1 and 2 cms., using the following parameters for its dimensions: the previous volume of the lips, and the distance between the two buccal commissures when in the "smile position."

A potential inhibitory function of draxin in regulating mouse trunk neural crest migration.

PubMed

Zhang, Sanbing; Su, Yuhong; Gao, Jinbao; Zhang, Chenbing; Tanaka, Hideaki

2017-01-01

Draxin is a repulsive axon guidance protein that plays important roles in the formation of three commissures in the central nervous system and dorsal interneuron 3 (dI3) in the chick spinal cord. In the present study, we report the expression pattern of mouse draxin in the embryonic mouse trunk spinal cord. In the presence of draxin, the longest net migration length of a migrating mouse trunk neural crest cell was significantly reduced. In addition, the relative number of apolar neural crest cells increased as the draxin treatment time increased. Draxin caused actin cytoskeleton rearrangement in the migrating trunk neural crest cells. Our data suggest that draxin may regulate mouse trunk neural crest cell migration by the rearrangement of cell actin cytoskeleton and by reducing the polarization activity of these cells subsequently.

[Method to make the tricuspid extracardiac conduit by heterogeneous pericardium].

PubMed

Yamagishi, M; Imai, Y; Koh, Y; Nagatsu, M; Matsuo, K; Kurosawa, H

1992-07-01

We described here, how to make tricuspid extracardiac conduit by heterogeneous pericardium for Rastelli procedure. We have developed some ingenious devices which allow to obtain good hemodynamics. One of the devices is large valvular leaflets as long as 130% of the circumference of the conduit. Another device is the commissural suture as figure of eight. We used 121 tricuspid extracardiac conduits between January 1985 and March 1991. There were two reoperations: One from stenosis at the suture with ventricle and the other from infective endocarditis. This hand-made conduit has the advantages of flexibility, fitness with the pulmonary artery, wide range of size and very little regurgitation. These advantages indicate that the tricuspid extracardiac conduit made by heterogeneous pericardium is a valved conduit substitute of choice for Rastelli procedure. The durability of the conduit is to be further evaluated.

Red blood cells open promising avenues for longitudinal studies of ageing in laboratory, non-model and wild animals.

PubMed

Stier, Antoine; Reichert, Sophie; Criscuolo, Francois; Bize, Pierre

2015-11-01

Ageing is characterized by a progressive deterioration of multiple physiological and molecular pathways, which impair organismal performance and increase risks of death with advancing age. Hence, ageing studies must identify physiological and molecular pathways that show signs of age-related deterioration, and test their association with the risk of death and longevity. This approach necessitates longitudinal sampling of the same individuals, and therefore requires a minimally invasive sampling technique that provides access to the larger spectrum of physiological and molecular pathways that are putatively associated with ageing. The present paper underlines the interest in using red blood cells (RBCs) as a promising target for longitudinal studies of ageing in vertebrates. RBCs provide valuable information on the following six pathways: cell maintenance and turnover (RBC number, size, and heterogeneity), glucose homeostasis (RBC glycated haemoglobin), oxidative stress parameters, membrane composition and integrity, mitochondrial functioning, and telomere dynamics. The last two pathways are specific to RBCs of non-mammalian species, which possess a nucleus and functional mitochondria. We present the current knowledge about RBCs and age-dependent changes in these pathways in non-model and wild species that are especially suitable to address questions related to ageing using longitudinal studies. We discuss how the different pathways relate with survival and lifespan and give information on their genetic and environmental determinants to appraise their evolutionary potential. Copyright © 2015 Elsevier Inc. All rights reserved.

Identification of novel loci for the generation of reporter mice

PubMed Central

Rebecchi, Monica; Levandis, Giovanna

2017-01-01

Abstract Deciphering the etiology of complex pathologies at molecular level requires longitudinal studies encompassing multiple biochemical pathways (apoptosis, proliferation, inflammation, oxidative stress). In vivo imaging of current reporter animals enabled the spatio-temporal analysis of specific molecular events, however, the lack of a multiplicity of loci for the generalized and regulated expression of the integrated transgenes hampers the creation of systems for the simultaneous analysis of more than a biochemical pathways at the time. We here developed and tested an in vivo-based methodology for the identification of multiple insertional loci suitable for the generation of reliable reporter mice. The validity of the methodology was tested with the generation of novel mice useful to report on inflammation and oxidative stress. PMID:27899606

Development of a series of aryl pyrimidine kynurenine monooxygenase inhibitors as potential therapeutic agents for the treatment of Huntington's disease.

PubMed

Toledo-Sherman, Leticia M; Prime, Michael E; Mrzljak, Ladislav; Beconi, Maria G; Beresford, Alan; Brookfield, Frederick A; Brown, Christopher J; Cardaun, Isabell; Courtney, Stephen M; Dijkman, Ulrike; Hamelin-Flegg, Estelle; Johnson, Peter D; Kempf, Valerie; Lyons, Kathy; Matthews, Kimberly; Mitchell, William L; O'Connell, Catherine; Pena, Paula; Powell, Kendall; Rassoulpour, Arash; Reed, Laura; Reindl, Wolfgang; Selvaratnam, Suganathan; Friley, Weslyn Ward; Weddell, Derek A; Went, Naomi E; Wheelan, Patricia; Winkler, Christin; Winkler, Dirk; Wityak, John; Yarnold, Christopher J; Yates, Dawn; Munoz-Sanjuan, Ignacio; Dominguez, Celia

2015-02-12

We report on the development of a series of pyrimidine carboxylic acids that are potent and selective inhibitors of kynurenine monooxygenase and competitive for kynurenine. We describe the SAR for this novel series and report on their inhibition of KMO activity in biochemical and cellular assays and their selectivity against other kynurenine pathway enzymes. We describe the optimization process that led to the identification of a program lead compound with a suitable ADME/PK profile for therapeutic development. We demonstrate that systemic inhibition of KMO in vivo with this lead compound provides pharmacodynamic evidence for modulation of kynurenine pathway metabolites both in the periphery and in the central nervous system.

Phylum-wide analysis of genes/proteins related to the last steps of assembly and export of extracellular polymeric substances (EPS) in cyanobacteria

NASA Astrophysics Data System (ADS)

Pereira, Sara B.; Mota, Rita; Vieira, Cristina P.; Vieira, Jorge; Tamagnini, Paula

2015-10-01

Many cyanobacteria produce extracellular polymeric substances (EPS) with particular characteristics (e.g. anionic nature and presence of sulfate) that make them suitable for industrial processes such as bioremediation of heavy metals or thickening, suspending or emulsifying agents. Nevertheless, their biosynthetic pathway(s) are still largely unknown, limiting their utilization. In this work, a phylum-wide analysis of genes/proteins putatively involved in the assembly and export of EPS in cyanobacteria was performed. Our results demonstrated that most strains harbor genes encoding proteins related to the three main pathways: Wzy-, ABC transporter-, and Synthase-dependent, but often not the complete set defining one pathway. Multiple gene copies are mainly correlated to larger genomes, and the strains with reduced genomes (e.g. the clade of marine unicellular Synechococcus and Prochlorococcus), seem to have lost most of the EPS-related genes. Overall, the distribution of the different genes/proteins within the cyanobacteria phylum raises the hypothesis that cyanobacterial EPS production may not strictly follow one of the pathways previously characterized. Moreover, for the proteins involved in EPS polymerization, amino acid patterns were defined and validated constituting a novel and robust tool to identify proteins with similar functions and giving a first insight to which polymer biosynthesis they are related to.

Metabolic gene clusters encoding the enzymes of two branches of the 3-oxoadipate pathway in the pathogenic yeast Candida albicans.

PubMed

Gérecová, Gabriela; Neboháčová, Martina; Zeman, Igor; Pryszcz, Leszek P; Tomáška, Ľubomír; Gabaldón, Toni; Nosek, Jozef

2015-05-01

The pathogenic yeast Candida albicans utilizes hydroxyderivatives of benzene via the catechol and hydroxyhydroquinone branches of the 3-oxoadipate pathway. The genetic basis and evolutionary origin of this catabolic pathway in yeasts are unknown. In this study, we identified C. albicans genes encoding the enzymes involved in the degradation of hydroxybenzenes. We found that the genes coding for core components of the 3-oxoadipate pathway are arranged into two metabolic gene clusters. Our results demonstrate that C. albicans cells cultivated in media containing hydroxybenzene substrates highly induce the transcription of these genes as well as the corresponding enzymatic activities. We also found that C. albicans cells assimilating hydroxybenzenes cope with the oxidative stress by upregulation of cellular antioxidant systems such as alternative oxidase and catalase. Moreover, we investigated the evolution of the enzymes encoded by these clusters and found that most of them share a particularly sparse phylogenetic distribution among Saccharomycotina, which is likely to have been caused by extensive gene loss. We exploited this fact to find co-evolving proteins that are suitable candidates for the missing enzymes of the pathway. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Targeting Mechanisms of Resistance to Taxane-Based Chemotherapy

DTIC Science & Technology

2007-09-01

gene ; monoamine oxidase A ( MAOA ) was upregulated in patients with PSA relapse (Figure 5A). Quantitative real-time PCR (qRT-PCR) was performed to...resistance and uncover mechanisms or pathways suitable for targeting with the objective of improving tumor responses to chemotherapy. Gene expression...CXCL10 but not IL8 conferring chemoresistance to prostate cancer cells. When using longer term clinical outcome, we found genes correlated with PSA

Microscope-integrated optical coherence tomography for image-aided positioning of glaucoma surgery

NASA Astrophysics Data System (ADS)

Li, Xiqi; Wei, Ling; Dong, Xuechuan; Huang, Ping; Zhang, Chun; He, Yi; Shi, Guohua; Zhang, Yudong

2015-07-01

Most glaucoma surgeries involve creating new aqueous outflow pathways with the use of a small surgical instrument. This article reported a microscope-integrated, real-time, high-speed, swept-source optical coherence tomography system (SS-OCT) with a 1310-nm light source for glaucoma surgery. A special mechanism was designed to produce an adjustable system suitable for use in surgery. A two-graphic processing unit architecture was used to speed up the data processing and real-time volumetric rendering. The position of the surgical instrument can be monitored and measured using the microscope and a grid-inserted image of the SS-OCT. Finally, experiments were simulated to assess the effectiveness of this integrated system. Experimental results show that this system is a suitable positioning tool for glaucoma surgery.

Developing integrated patient pathways using hybrid simulation

NASA Astrophysics Data System (ADS)

Zulkepli, Jafri; Eldabi, Tillal

2016-10-01

Integrated patient pathways includes several departments, i.e. healthcare which includes emergency care and inpatient ward; intermediate care which patient(s) will stay for a maximum of two weeks and at the same time be assessed by assessment team to find the most suitable care; and social care. The reason behind introducing the intermediate care in western countries was to reduce the rate of patients that stays in the hospital especially for elderly patients. This type of care setting has been considered to be set up in some other countries including Malaysia. Therefore, to assess the advantages of introducing this type of integrated healthcare setting, we suggest develop the model using simulation technique. We argue that single simulation technique is not viable enough to represent this type of patient pathways. Therefore, we suggest develop this model using hybrid techniques, i.e. System Dynamics (SD) and Discrete Event Simulation (DES). Based on hybrid model result, we argued that the result is viable to be as references for decision making process.

The ipdC, hisC1 and hisC2 genes involved in indole-3-acetic production used as alternative phylogenetic markers in Azospirillum brasilense.

PubMed

Jijón-Moreno, Saúl; Marcos-Jiménez, Cynthia; Pedraza, Raúl O; Ramírez-Mata, Alberto; de Salamone, I García; Fernández-Scavino, Ana; Vásquez-Hernández, Claudia A; Soto-Urzúa, Lucia; Baca, Beatriz E

2015-06-01

Plant growth-promoting bacteria of the genus Azospirillum are present in the rhizosphere and as endophytes of many crops. In this research we studied 40 Azospirillum strains isolated from different plants and geographic regions. They were first characterized by 16S rDNA restriction analysis, and their phylogenetic position was established by sequencing the genes 16S rDNA, ipdC, hisC1, and hisC2. The latter three genes are involved in the indole-3-pyruvic acid (IPyA) biosynthesis pathway of indole-3-acetic acid (IAA). Furthermore, the suitability of the 16S-23S rDNA intergenic spacer sequence (IGS) for the differentiation of closely related Azospirillum taxa and development of PCR protocols allows for specific detection of strains. The IGS-RFLP analysis enabled intraspecies differentiation, particularly of Azospirillum brasilense and Azospirillum lipoferum strains. Results demonstrated that the ipdC, hisC1, and hisC2 genes are highly conserved in all the assessed A. brasilense isolates, suggesting that these genes can be used as an alternative phylogenetic marker. In addition, IAA production determined by HPLC ranged from 0.17 to 98.2 μg mg(-1) protein. Southern hybridization with the A. brasilense ipdC gene probe did not show, a hybridization signal with A. lipoferum, Azospirillum amazonense, Azospirillum halopreferans and Azospirillum irakense genomic DNA. This suggests that these species produce IAA by other pathways. Because IAA is mainly synthesized via the IPyA pathway in A. brasilense strains, a species that is used worldwide in agriculture, the identification of ipdC, hisC1, and hisC2 genes by PCR may be suitable for selecting exploitable strains.

A rapid method for the extraction and analysis of carotenoids and other hydrophobic substances suitable for systems biology studies with photosynthetic bacteria.

PubMed

Bóna-Lovász, Judit; Bóna, Aron; Ederer, Michael; Sawodny, Oliver; Ghosh, Robin

2013-10-11

A simple, rapid, and inexpensive extraction method for carotenoids and other non-polar compounds present in phototrophic bacteria has been developed. The method, which has been extensively tested on the phototrophic purple non-sulphur bacterium Rhodospirillum rubrum, is suitable for extracting large numbers of samples, which is common in systems biology studies, and yields material suitable for subsequent analysis using HPLC and mass spectroscopy. The procedure is particularly suitable for carotenoids and other terpenoids, including quinones, bacteriochlorophyll a and bacteriopheophytin a, and is also useful for the analysis of polar phospholipids. The extraction procedure requires only a single step extraction with a hexane/methanol/water mixture, followed by HPLC using a Spherisorb C18 column, with a mobile phase consisting of acetone-water and a non-linear gradient of 50%-100% acetone. The method was employed for examining the carotenoid composition observed during microaerophilic growth of R. rubrum strains, and was able to determine 18 carotenoids, 4 isoprenoid-quinones, bacteriochlorophyll a and bacteriopheophytin a as well as four different phosphatidylglycerol species of different acyl chain compositions. The analytical procedure was used to examine the dynamics of carotenoid biosynthesis in the major and minor pathways operating simultaneously in a carotenoid biosynthesis mutant of R. rubrum.

Anticipated effects of development on habitat fragmentation and movement of mammals into and out of the Schoodic District, Acadia National Park, Maine

USGS Publications Warehouse

Rohweder, Jason J.; De Jager, Nathan R.; Guntenspergen, Glenn R.

2012-01-01

Most national parks interact with adjacent lands because their boundaries fail to encompass all regional habitats, species pools, and migration routes. Activities planned for adjacent lands can have adverse effects on park resources and visitor experiences. For example, fragmentation of adjacent habitat into smaller and more isolated remnants may influence the suitability of park habitat for a wide range of species and limit animal dispersal pathways, which may influence visitor experiences and park resources as well as the energy balance and population dynamics of the animals themselves. In this study, we examined habitat fragmentation consequences owing to a planned 1,295 hectare development by Winter Harbor Holding Company (WHHC) adjacent to the Schoodic District of Acadia National Park (ANP), Maine. Specifically, we examined the effects of development on (a) core natural habitat area (a cross-habitat indicator of fragmentation), (b) the suitability of habitat for bobcat, fisher, mink, and moose, and (c) the movement of these four species between ANP and other nearby protected areas (species specific indicators of fragmentation). Our intention was to assist ANP staff in forecasting both the general and specific effects of development on natural habitat area, habitat suitability, and animal movement, which would allow them to develop suitable management alternatives.

Effects of a Protic Ionic Liquid on the Reaction Pathway during Non-Aqueous Sol–Gel Synthesis of Silica: A Raman Spectroscopic Investigation

PubMed Central

Martinelli, Anna

2014-01-01

The reaction pathway during the formation of silica via a two-component “non-aqueou” sol-gel synthesis is studied by in situ time-resolved Raman spectroscopy. This synthetic route is followed with and without the addition of the protic ionic liquid 1-ethylimidazolium bis(trifluoromethanesulfonyl)imide (C2HImTFSI) in order to investigate its effect on the reaction pathway. We demonstrate that Raman spectroscopy is suitable to discriminate between different silica intermediates, which are produced and consumed at different rates with respect to the point of gelation. We find that half-way to gelation monomers and shorter chains are the most abundant silica species, while the formation of silica rings strongly correlates to the sol-to-gel transition. Thus, curling up of linear chains is here proposed as a plausible mechanism for the formation of small rings. These in turn act as nucleation sites for the condensation of larger rings and thus the formation of the open and polymeric silica network. We find that the protic ionic liquid does not change the reaction pathway per se, but accelerates the cyclization process, intermediated by the faster inclusion of monomeric species. PMID:24743891

Evaluation of the pentose phosphate pathway from 14CO2 data. Fallibility of a classic equation when applied to non-homogeneous tissues.

PubMed

Larrabee, M G

1990-11-15

A classic equation that has frequently been used to estimate the fraction of glucose metabolized by the pentose phosphate pathway, using 14CO2 data, is more simply re-derived with careful consideration of the assumptions involved and the conditions under which it is applicable. The equation is shown to be unreliable for non-homogeneous tissues, depending on the fraction of triose phosphate converted to CO2. The formula in question is as follows: ([1]CO2/G-[6]CO2/G)/(1-[6]CO2/G) = 3Fmet./(1 + 2Fmet.) where [1]CO2 and [6]CO2 are output rates of carbons 1 and 6 of glucose respectively to CO2, G is the rate of glucose uptake and Fmet. is the fraction of the glucose that is metabolized to CO2 and triose phosphate by the pentose phosphate pathway, allowing for recycling of an appropriate fraction of the fructose-6-phosphate produced by the pathway. This analysis illustrates the importance of suitably testing any equation that assumes homogeneity before application to non-homogeneous tissues.

Transcriptomic analysis in the developing zebrafish embryo after compound exposure: Individual gene expression and pathway regulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hermsen, Sanne A.B., E-mail: Sanne.Hermsen@rivm.nl; Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht; Institute for Risk Assessment Sciences

2013-10-01

The zebrafish embryotoxicity test is a promising alternative assay for developmental toxicity. Classically, morphological assessment of the embryos is applied to evaluate the effects of compound exposure. However, by applying differential gene expression analysis the sensitivity and predictability of the test may be increased. For defining gene expression signatures of developmental toxicity, we explored the possibility of using gene expression signatures of compound exposures based on commonly expressed individual genes as well as based on regulated gene pathways. Four developmental toxic compounds were tested in concentration-response design, caffeine, carbamazepine, retinoic acid and valproic acid, and two non-embryotoxic compounds, D-mannitol andmore » saccharin, were included. With transcriptomic analyses we were able to identify commonly expressed genes, which were mostly development related, after exposure to the embryotoxicants. We also identified gene pathways regulated by the embryotoxicants, suggestive of their modes of action. Furthermore, whereas pathways may be regulated by all compounds, individual gene expression within these pathways can differ for each compound. Overall, the present study suggests that the use of individual gene expression signatures as well as pathway regulation may be useful starting points for defining gene biomarkers for predicting embryotoxicity. - Highlights: • The zebrafish embryotoxicity test in combination with transcriptomics was used. • We explored two approaches of defining gene biomarkers for developmental toxicity. • Four compounds in concentration-response design were tested. • We identified commonly expressed individual genes as well as regulated gene pathways. • Both approaches seem suitable starting points for defining gene biomarkers.« less

Carcinoma of the larynx: role of laser surgery

NASA Astrophysics Data System (ADS)

Inouye, Tetsuzo; Tanabe, Tetsuya; Nakanoboh, Manabu; Ohmae, Yukio; Ogura, Masami

1995-05-01

68 cases of glottic carcinomas (T1 53 and T2 15 cases) treated with CO2 laser or KTP/532 laser April 1982 through March 1992 were reviewed. The patients were followed up from 13 to 130 months (mean 60 months). The 3-year determinate survival rate was 100% and 5-year determinate survival rate was 100% for T1 and 80% for T2. The voice conservation rate was 97% for T1a, 83% for T1b, and 80% for T2 and vocal function was satisfactorily preserved for daily life. The results led to the following conclusions: (1) Glottic T1 carcinomas can be treated by laser surgery alone. (2) Lesions involving the anterior commissure can be treated by laser excision and vaporization. (3) Laser surgery followed by external radiation therapy for glottic T2 carcinomas improves the voice conservation rate.

Fgfr3 regulates development of the caudal telencephalon.

PubMed

Moldrich, Randal X; Mezzera, Cecilia; Holmes, William M; Goda, Sailaja; Brookfield, Sam J; Rankin, Alastair J; Barr, Emily; Kurniawan, Nyoman; Dewar, Deborah; Richards, Linda J; López-Bendito, Guillermina; Iwata, Tomoko

2011-06-01

The fibroblast growth factor receptor 3 (Fgfr3) is expressed in a rostral(low) to caudal(high) gradient in the developing cerebral cortex. Therefore, we hypothesized that Fgfr3 contributes to the correct morphology and connectivity of the caudal cortex. Overall, the forebrain structures appeared normal in Fgfr3(-/-) mice. However, cortical and hippocampal volumes were reduced by 26.7% and 16.3%, respectively. Hypoplasia was particularly evident in the caudo-ventral region of the telencephalon where proliferation was mildly decreased at embryonic day 18.5. Dysplasia of GABAergic neurons in the amygdala and piriform cortex was seen following GAD67 immunohistochemistry. Dye-tracing studies and diffusion magnetic resonance imaging and tractography detected a subtle thalamocortical tract deficit, and significant decreases in the stria terminalis and lateral arms of the anterior commissure. These results indicate the subtle role of Fgfr3 in formation of caudal regions of the telencephalon affecting some brain projections. Copyright © 2011 Wiley-Liss, Inc.

brother of cdo (umleitung) is cell-autonomously required for Hedgehog-mediated ventral CNS patterning in the zebrafish

PubMed Central

Bergeron, Sadie A.; Tyurina, Oksana V.; Miller, Emily; Bagas, Andrea; Karlstrom, Rolf O.

2011-01-01

The transmembrane protein Brother of Cdo (Boc) has been implicated in Shh-mediated commissural axon guidance, and can both positively and negatively regulate Hedgehog (Hh) target gene transcription, however, little is known about in vivo requirements for Boc during vertebrate embryogenesis. The zebrafish umleitung (umlty54) mutant was identified by defects in retinotectal axon projections. Here, we show that the uml locus encodes Boc and that Boc function is cell-autonomously required for Hh-mediated neural patterning. Our phenotypic analysis suggests that Boc is required as a positive regulator of Hh signaling in the spinal cord, hypothalamus, pituitary, somites and upper jaw, but that Boc might negatively regulate Hh signals in the lower jaw. This study reveals a role for Boc in ventral CNS cells that receive high levels of Hh and uncovers previously unknown roles for Boc in vertebrate embryogenesis. PMID:21115611

Clinical course of acute laryngeal trauma and associated effects on phonation.

PubMed

Brosch, S; Johannsen, H S

1999-01-01

We report the clinical course of blunt laryngeal trauma in three young patients. All three patients underwent several phoniatric examinations as well as indirect microlaryngoscopy and microstroboscopy. The follow-up period ranged from three to eight months. In the first case, there was isolated haemorrhage of the left vocal fold; in the second, dislocation of the arytenoid cartilage with formation of an adhesion in the area of the anterior commissure; and, in the third, non-dislocated fracture of the thyroid cartilage with development of haematoma in the right hemilarynx and transient vocal fold paralysis. One patient required surgical treatment; however, repositioning of the arytenoid cartilage, attempted seven weeks following the injury, proved unsuccessful. In conclusion, all three patients showed significant limitation of vocal fold vibration many months after trauma which was unrelated to the extent of resulting tissue damage. In all three cases, patients developed secondary posttraumatic functional dysphonia requiring treatment.

Dandy Walker Syndrome with Tessier 7 Cleft-a Rare Case Report and a Surgical Note on the Use of Vermilion Flap and Lazy W-Plasty.

PubMed

Dhupar, Vikas; Kumar, Praveen; Akkara, Francis; Kumar, Ananth

2012-09-01

The Dandy-Walker syndrome is a malformation of the brain that involves the mal-development of the cerebellum, associated with a cystic enlargement of this area, and frequently hydrocephalus. This malformation occurs in ~1 in 30,000 babies. It is seen mostly in females. Developmental anomalies like cleft lip, cleft palate, and cardiac malformation, orthopaedic and urinary structural abnormalities may also occur in 30% of the individuals. We report a case of Dandy Walker syndrome with Tessier 7 facial cleft with paramedian cleft palate in a 6 month old child. Surgical methods used to correct this anomaly include commissuroplasty, myoplasty of the orbicularis oris, and closure of the cleft cheek. Authors report a vermilion square flap technique that combines a lower lip mucocutaneous vermilion border flap with a lazy W-plasty to ensure a natural commissure and skin closure.

Staphylococcal dermatitis in quail with a parakeratotic hyperkeratotic dermatosis suggestive of pantothenic acid deficiency.

PubMed

Raidal, S R

1995-09-01

This report describes an outbreak of Staphylococcal dermatitis which occurred in commercial Japanese quail (Coturnix coturnix japonica) with a history and clinico-pathological evidence suggestive of pantothenic acid deficiency. The flock had a low hatchability rate (40 to 43%) and a high percentage (50%) of dead-in-shell embryos. Approximately 5 to 15% of the grower flock developed crusty facial scabs and conjunctivitis from 4 days of age. Culture of eyelid skin yielded pure growths of non-haemolytic, coagulase-negative Staphylococcus spp. Histological examination revealed a generalised hyperkeratosis and parakeratosis of feathers, feather follicles and non-follicular skin. There was invasion of feather follicles by cocci and focal areas of suppurative exudative dermatitis and subcutaneous abscesses particularly in the eyelids and commissures of the beak. Clinical signs were alleviated by treatment with amoxycillin and a change in ration formulation.

Central projections of the nervus terminalis in four species of amphibians.

PubMed

Hofmann, M H; Meyer, D L

1989-01-01

The central projections of the nervus terminalis were investigated in two anuran and two urodele species by means of horseradish peroxidase injections into one nasal cavity. In anurans, the nervus terminalis projects to the medial septum, to the preoptic nucleus, to the nucleus of the anterior commissure and to the hypothalamus. In addition to these structures, the dorsal thalamus, the infundibulum and the mesencephalic tegmentum are innervated in urodeles. The structure containing the highest density of terminals in the amphibians investigated is the hypothalamus. In one anuran and one urodele species, the contralateral hypothalamus is primarily innervated, whereas in the other two species the majority of fibers remain ipsilateral. A comparison with other vertebrates shows that the terminalis system in urodeles has the greatest diversity of connections. Anurans, in contrast, lack some connections that are present in urodeles and fishes. These findings have implications for a possible relation of the nervus terminalis to an aquatic habitat.

Visual interhemispheric communication and callosal connections of the occipital lobes.

PubMed

Berlucchi, Giovanni

2014-07-01

Callosal connections of the occipital lobes, coursing in the splenium of the corpus callosum, have long been thought to be crucial for interactions between the cerebral hemispheres in vision in both experimental animals and humans. Yet the callosal connections of the temporal and parietal lobes appear to have more important roles than those of the occipital callosal connections in at least some high-order interhemispheric visual functions. The partial intermixing and overlap of temporal, parietal and occipital callosal connections within the splenium has made it difficult to attribute the effects of splenial pathological lesions or experimental sections to splenial components specifically related to select cortical areas. The present review describes some current contributions from the modern techniques for the tracking of commissural fibers within the living human brain to the tentative assignation of specific visual functions to specific callosal tracts, either occipital or extraoccipital. Copyright © 2013 Elsevier Ltd. All rights reserved.

Optimizing MR imaging-guided navigation for focused ultrasound interventions in the brain

NASA Astrophysics Data System (ADS)

Werner, B.; Martin, E.; Bauer, R.; O'Gorman, R.

2017-03-01

MR imaging during transcranial MR imaging-guided Focused Ultrasound surgery (tcMRIgFUS) is challenging due to the complex ultrasound transducer setup and the water bolus used for acoustic coupling. Achievable image quality in the tcMRIgFUS setup using the standard body coil is significantly inferior to current neuroradiologic standards. As a consequence, MR image guidance for precise navigation in functional neurosurgical interventions using tcMRIgFUS is basically limited to the acquisition of MR coordinates of salient landmarks such as the anterior and posterior commissure for aligning a stereotactic atlas. Here, we show how improved MR image quality provided by a custom built MR coil and optimized MR imaging sequences can support imaging-guided navigation for functional tcMRIgFUS neurosurgery by visualizing anatomical landmarks that can be integrated into the navigation process to accommodate for patient specific anatomy.

Substance P binding sites in the nucleus tractus solitarius of the cat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maley, B.E.; Sasek, C.A.; Seybold, V.S.

1988-11-01

Substance P binding sites in the nucleus tractus solitarius were visualized with receptor autoradiography using Bolton-Hunter (/sup 125/I)substance P. Substance P binding sites were found to have distinct patterns within the cat nucleus tractus solitarius. The majority of substance P binding sites were present in the medial, intermediate and the peripheral rim of the parvocellular subdivisions. Lower amounts of substance P binding sites were present in the commissural, ventrolateral, interstitial and dorsolateral subdivisions. No substance P binding sites were present in the central region of the parvocellular subdivision or the solitary tract. The localization of substance P binding sites inmore » the nucleus tractus solitarius is very similar to the patterns of substance P immunoreactive fibers previously described for this region. Results of this study add further support for a functional role of substance P in synaptic circuits of the nucleus tractus solitarius.« less

Effects of insulin-like growth factor 1 on pathologic processes in the cuprizone model of multiple sclerosis

NASA Astrophysics Data System (ADS)

Fedorishin, D.; Sorokina, I.; Tolstikova, T.; Akulov, A.; Glazacheva, V.; Nemirovich-Danchenko, N.; Khodanovich, M.; Yarnykh, V.

2017-08-01

The study aims to evaluate the effect of insulin-like growth factor 1 (IGF-1) on the demyelination and astrogliosis using the cuprizone murine model. Demyelination was induced in 14 adult male mice by 0.3% cuprizone in drinking water. Five animals from the cuprizone-treated group received subcutaneous injections of IGF-1. Seven animals were used as a control group. The extent of demyelination was evaluated as a decrease in the size of the corpus callosum on T2-weighted images that were received using an 11.7T animal MRI scanner. Brain sections were immunohistochemically stained for glial fibrillary acidic protein (GFAP), a marker of astrocytes. It was revealed that the cuprizone caused extensive demyelination and astroglyosis. IGF-1 treatment restored the size of the corpus callosum and the number of astrocytes in the corpus callosum and the anterior commissure to the control level.

A rare cause of lateral facial swelling.

PubMed

Mohanty, Sujata; Gulati, Ujjwal; Vandana; Singh, Sapna

2014-01-01

A case of chronic, recurrent and asymptomatic facial swelling in a young male is presented. Swelling extended from lower midface to upper lateral neck and right commissure to anterior massetric border. History, clinical signs and symptoms and examination pointed towards the benign nature of the swelling. Fine-needle aspiration cytology tapered the diagnostic possibilities to a salivary cyst or pseudocyst. Ultrasonography identified the lesion to contain echogenic fluid with irregular borders. "Tail sign" was absent on contrast magnetic resonance imaging, excluding the involvement of the sublingual gland. Surgical excision of the lesion was done along with submandibular gland as both were in continuity via a bottle-neck tract. Final histopathological diagnosis was that of the submandibular gland extravasation phenomenon. As per the best of our knowledge, it is the first case report of a submandibular gland extravasation causing swelling in a retrograde direction onto the face.

A rare cause of lateral facial swelling

PubMed Central

Mohanty, Sujata; Gulati, Ujjwal; Vandana; Singh, Sapna

2014-01-01

A case of chronic, recurrent and asymptomatic facial swelling in a young male is presented. Swelling extended from lower midface to upper lateral neck and right commissure to anterior massetric border. History, clinical signs and symptoms and examination pointed towards the benign nature of the swelling. Fine-needle aspiration cytology tapered the diagnostic possibilities to a salivary cyst or pseudocyst. Ultrasonography identified the lesion to contain echogenic fluid with irregular borders. “Tail sign” was absent on contrast magnetic resonance imaging, excluding the involvement of the sublingual gland. Surgical excision of the lesion was done along with submandibular gland as both were in continuity via a bottle-neck tract. Final histopathological diagnosis was that of the submandibular gland extravasation phenomenon. As per the best of our knowledge, it is the first case report of a submandibular gland extravasation causing swelling in a retrograde direction onto the face. PMID:25593883

An uncommon cause of tricuspid regurgitation: three-dimensional echocardiographic incremental value, surgical and genetic insights.

PubMed

Theron, Alexis; Pinard, Amélie; Riberi, Alberto; Zaffran, Stéphane

2016-07-01

Congenital tricuspid valve disease is a rare defect that includes regurgitation, stenosis and Ebstein's anomaly. We report a case of severe tricuspid regurgitation associated with functional mitral regurgitation in a 47-year-old man with congestive heart failure. Transthoracic echocardiography (TTE) ruled out any Ebstein's anomaly. Three-dimensional TTE revealed a 'tricuspid hole' into the anterior leaflet that was only attached to the tricuspid annulus next to both anteroseptal and anteroposterior commissures. There was no sign of leaflet tear or perforation. The surgical repair of the tricuspid and mitral valves was performed with an optimal result. No sign of endocarditis or rheumatic disease was observed during the intervention. Sequence analysis of GATA4, HEY2 and ZFPM2 genes was performed, but no causative mutation was identified. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

The horizontal optokinetic reflex of the opossum (Didelphis marsupialis aurita): physiological and anatomical studies in normal and early monoenucleated specimens.

PubMed

Nasi, J P; Volchan, E; Tecles, M T; Bernardes, R F; Rocha-Miranda, C E

1997-05-01

In the opossum the symmetrical binocular horizontal optokinetic nystagmus gives way to an asymmetrical monocular reflex: the nasotemporal (NT) stimulation yielding lower gain than the temporonasal (TN). In adults, monocularly enucleated at postnatal days 21-25 (pnd21-25), the gain of NT responses is markedly increased, approaching that of TN. Severe cell loss was detected in the nucleus of the optic tract (NOT) on the deafferented side in early monoenucleated specimens. In normal animals retinal afferents to the NOT are all crossed, while in animals enucleated at pnd21-25 sparse uncrossed retinal elements were observed. Although this abnormal projection might influence the increased NT response in this subgroup, it is argued that the increased symmetry in monoenucleated opossums may be the result of changes mediated by the commissural connection between both NOTs.

The accidental introduction of invasive animals as hitchhikers through inanimate pathways: a New Zealand perspective.

PubMed

Toy, S J; Newfield, M J

2010-04-01

Hitchhiker organisms have been known since the earliest days of international travel, but changes in global trade mean that there are more now than ever before. They include a number of serious invasive species and are among the most difficult of quarantine problems to manage. Invasive animals transported as hitchhikers, other than plant pests, fall largely outside the international frameworks for biosecurity risk analysis. However, this is not necessarily a barrierto either risk analysis or effective management. While there are a number of challenges in managing hitchhiker organisms, the risk analysis tools that are needed already exist. However, opening up access to appropriate information, increasing international cooperation and developing new biosecurity treatments suitable for large-volume pathways will enable significant improvements.

Fluorescence-based high-throughput screening of dicer cleavage activity.

PubMed

Podolska, Katerina; Sedlak, David; Bartunek, Petr; Svoboda, Petr

2014-03-01

Production of small RNAs by ribonuclease III Dicer is a key step in microRNA and RNA interference pathways, which employ Dicer-produced small RNAs as sequence-specific silencing guides. Further studies and manipulations of microRNA and RNA interference pathways would benefit from identification of small-molecule modulators. Here, we report a study of a fluorescence-based in vitro Dicer cleavage assay, which was adapted for high-throughput screening. The kinetic assay can be performed under single-turnover conditions (35 nM substrate and 70 nM Dicer) in a small volume (5 µL), which makes it suitable for high-throughput screening in a 1536-well format. As a proof of principle, a small library of bioactive compounds was analyzed, demonstrating potential of the assay.

The biology of Mur ligases as an antibacterial target.

PubMed

Kouidmi, Imène; Levesque, Roger C; Paradis-Bleau, Catherine

2014-10-01

With antibiotic resistance mechanisms increasing in diversity and spreading among bacterial pathogens, the development of new classes of antibacterial agents against judiciously chosen targets is a high-priority task. The biochemical pathway for peptidoglycan biosynthesis is one of the best sources of antibacterial targets. Within this pathway are the Mur ligases, described in this review as highly suitable targets for the development of new classes of antibacterial agents. The amide ligases MurC, MurD, MurE and MurF function with the same catalytic mechanism and share conserved amino acid regions and structural features that can conceivably be exploited for the design of inhibitors that simultaneously target more than one enzyme. This would provide multi-target antibacterial weapons with minimized likelihood of target-mediated resistance development. © 2014 John Wiley & Sons Ltd.

Gene silencing pathway RNA-dependent RNA polymerase of Neurospora crassa: yeast expression and crystallization of selenomethionated QDE-1 protein.

PubMed

Laurila, Minni R L; Salgado, Paula S; Makeyev, Eugene V; Nettelship, Joanne; Stuart, David I; Grimes, Jonathan M; Bamford, Dennis H

2005-01-01

The RNA-dependent RNA polymerase, QDE-1, is a component of the RNA silencing pathway in Neurospora crassa. The enzymatically active carboxy-terminal fragment QDE-1 DeltaN has been expressed in Saccharomyces cerevisiae in the presence and absence of selenomethionine (SeMet). The level of SeMet incorporation was estimated by mass spectrometry to be approximately 98%. Both native and SeMet proteins were crystallized in space group P2(1) with unit cell parameters a=101.2, b=122.5, c=114.4A, beta=108.9 degrees , and 2 molecules per asymmetric unit. The native and SeMet crystals diffract to 2.3 and 3.2A, respectively, the latter are suitable for MAD structure determination.

METABOLIC ENGINEERING TO DEVELOP A PATHWAY FOR THE SELECTIVE CLEAVAGE OF CARBON-NITROGEN BONDS

DOE Office of Scientific and Technical Information (OSTI.GOV)

John J. Kilbane II

The objective of the project is to develop biochemical pathways for the selective cleavage of C-N bonds in molecules found in petroleum. The initial phase of the project was focused on the isolation or development of an enzyme capable of cleaving the C-N bond in aromatic amides, specifically 2-aminobiphenyl. The objective of the second phase of the research will be to construct a biochemical pathway for the selective removal of nitrogen from carbazole by combining the carA genes from Sphingomonas sp. GTIN11 with the gene(s) encoding an appropriate deaminase. The objective of the final phase of the project will bemore » to develop derivative C-N bond cleaving enzymes that have broader substrate ranges and to demonstrate the use of such strains to selectively remove nitrogen from petroleum. During the first year of the project (October, 2002-September, 2003) enrichment culture experiments resulted in the isolation of microbial cultures that utilize aromatic amides as sole nitrogen sources, several amidase genes were cloned and were included in directed evolution experiments to obtain derivatives that can cleave C-N bonds in aromatic amides, and the carA genes from Sphingomonas sp. GTIN11, and Pseudomonas resinovorans CA10 were cloned in vectors capable of replicating in Escherichia coli. During the second year of the project (October, 2003-September, 2004) enrichment culture experiments succeeded in isolating a mixed bacterial culture that can utilize 2-aminobiphenyl as a sole nitrogen source, directed evolution experiments were focused on the aniline dioxygenase enzyme that is capable of deaminating aniline, and expression vectors were constructed to enable the expression of genes encoding C-N bond cleaving enzymes in Rhodococcus hosts. The construction of a new metabolic pathway to selectively remove nitrogen from carbazole and other molecules typically found in petroleum should lead to the development of a process to improve oil refinery efficiency by reducing the poisoning, by nitrogen, of catalysts used in the hydrotreating and catalytic cracking of petroleum. Aromatic compounds such as carbazole are representative of the difficult-to-treat organonitrogen compounds most commonly encountered in petroleum. There are two C-N bonds in carbazole and the construction of a metabolic pathway for the removal of nitrogen from carbazole will require enzymes capable cleaving both C-N bonds. A multi-component enzyme, carbazole dioxygenase, which can selectively cleave the first C-N bond has been identified and the genes that encode this enzyme have been cloned, sequenced, and are being expressed in Rhodococcus erythropolis, a bacterial culture that tolerates exposure to petroleum. An enzyme capable of selectively cleaving the second C-N bond in carbazole has not yet been identified, but enrichment culture experiments have recently succeeded in isolating a bacterial culture that is a likely candidate and may possess a suitable enzyme. Research in the near future will verify if a suitable enzyme for the cleavage of the second C-N bond in carbazole has indeed been found, then the genes encoding a suitable enzyme will be identified, cloned, and sequenced. Ultimately genes encoding enzymes for selective cleavage of both C-N bonds in carbazole will be assembled into a new metabolic pathway and the ability of the resulting bacterial culture to remove nitrogen from petroleum will be determined.« less

Enhanced sampling molecular dynamics simulation captures experimentally suggested intermediate and unfolded states in the folding pathway of Trp-cage miniprotein.

PubMed

Shao, Qiang; Shi, Jiye; Zhu, Weiliang

2012-09-28

The ability of molecular dynamics simulation to capturing the transient states within the folding pathway of protein is important to the understanding of protein folding mechanism. In the present study, the integrated-tempering-sampling molecular dynamics (ITS-MD) simulation was performed to investigate the transient states including intermediate and unfolded ones in the folding pathway of a miniprotein, Trp-cage. Three force fields (FF03, FF99SB, and FF96) were tested, and both intermediate and unfolded states with their characteristics in good agreement with experiments were observed during the simulations, which supports the hypothesis that observable intermediates might present in the folding pathway of small polypeptides. In addition, it was demonstrated that FF03 force field as combined with ITS-MD is in overall a more proper force field than the others in reproducing experimentally recorded properties in UVRS, ECD, and NMR, Photo-CIDNP NMR, and IR T-jump experiments, and the folding∕unfolding thermodynamics parameters, such as ΔG(U), ΔC(p), and ΔH(U) (T(m)). In summary, the present study showed that using suitable force field and energy sampling method, molecular dynamics simulation could capture the transient states within the folding pathway of protein which are consistent with the experimental measurements, and thus provide information of protein folding mechanism and thermodynamics.

Repair of Parachute and Hammock Valve in Infants and Children: Early and Late Outcomes.

PubMed

Delmo Walter, Eva Maria; Javier, Mariano; Hetzer, Roland

2016-01-01

Parachute and hammock valves in children remain one of the most challenging congenital malformations to correct. We report our institutional experience with valve-preserving repair techniques and the early and late surgical outcomes in parachute and hammock valves in infants and children. From January 1990-June 2014, 20 infants and children with parachute (n = 12, median age = 2.5 years, range: 2 months-13 years) and hammock (n = 8, median age = 7 months, range: 1 month-14.9 years) valves underwent mitral valve (MV) repair. Children with parachute valves have predominant stenosis, whereas those with hammock valves often have predominant insufficiency. Intraoperative findings included fused and shortened chordae with single papillary muscles in children with parachute valves. MV repair was performed using annuloplasty, commissurotomy, leaflet incision toward the body of the papillary muscles, and split toward its base. Children with hammock valves have dysplastic and shortened chordae, absence of papillary muscles with fused and thickened commissures. MV repair consisted of carving off a suitably thick part of the left ventricular wall carrying the rudimentary chordae. The degree and extent of incision and commissurotomy is determined by the minimal age-related acceptable MV diameter to avoid mitral stenosis. During a median duration of follow-up of 9.6 years (range: 6.4-21.4 years), cumulative survival rate and freedom from reoperation in parachute valves were 43.7 ± 1.6% and 53.0 ± 1.8%, respectively. In hammock valves, during a median duration of follow-up of 6.7 years (range: 2.7-19.4 years), cumulative survival rate and freedom from reoperation was 72.9 ± 1.6% and 30.0 ± 1.7%, respectively. Age less than 1 year proved to be a high-risk factor for reoperation and mortality (P < 0.005). In conclusion, children with parachute and hammock valves, repeat MV repair may be necessary during the course of follow-up. Infants have a greater risk for reoperation and mortality. Copyright © 2016 Elsevier Inc. All rights reserved.

Physiological properties of anatomically identified basket and bistratified cells in the CA1 area of the rat hippocampus in vitro.

PubMed

Buhl, E H; Szilágyi, T; Halasy, K; Somogyi, P

1996-01-01

Basket and bistratified cells form two anatomically distinct classes of GABAergic local-circuit neurons in the CA1 region of the rat hippocampus. A physiological comparison was made of intracellularly recorded basket (n = 13) and bistratified neurons (n = 6), all of which had been anatomically defined by their efferent target profile (Halasy et al., 1996). Basket cells had an average resting membrane potential of -64.2 +/- 7.2 vs. -69.2 +/- 4.6 mV in bistratified cells. The latter had considerably higher mean input resistances (60.2 +/- 42.1 vs. 31.3 +/- 10.9 M Ohms) and longer membrane time constants (18.6 +/- 8.1 vs. 9.8 +/- 4.5 ms) than basket cells. Differences were also apparent in the duration of action potentials, those of basket cells being 364 +/- 77 and those of bistratified cells being 527 +/- 138 microseconds at half-amplitude. Action potentials were generally followed by prominent, fast after-hyperpolarizing potentials which in basket cells were 13.5 +/- 6.7 mV in amplitude vs. 10.5 +/- 5.1 in bistratified cells. The differences in membrane time constant, resting membrane potential, and action potential duration reached statistical significance (P < 0.05). Extracellular stimulation of Schaffer collateral/commissural afferents elicited short-latency excitatory postsynaptic potentials (EPSPs) in both cell types. The average 10-90% rise time and duration (at half-amplitude) of subthreshold EPSPs in basket cells were 1.9 +/- 0.5 and 10.7 +/- 5.6 ms, compared to 3.3 +/- 1.3 and 20.1 +/- 9.7 ms in bistratified cells, the difference in EPSP rise times being statistically significant. Basket and bistratified EPSPs were highly sensitive to a bath applied antagonist of non-N-methyl-D-aspartate (NMDA) receptors, whereas the remaining slow-rise EPSP could be abolished by an NMDA receptor antagonist. Increasing stimulation intensity elicited biphasic inhibitory postsynaptic potentials (IPSPs) in both basket and bistratified cells. In conclusion, basket and bistratified cells in the CA1 area show prominent differences in several of their membrane and firing properties. Both cell classes are activated by Schaffer collateral/commissural axons in a feedforward manner and receive inhibitory input from other, as yet unidentified, local-circuit neurons.

Induction of Jasmonic Acid-Associated Defenses by Thrips Alters Host Suitability for Conspecifics and Correlates with Increased Trichome Densities in Tomato

PubMed Central

Klinkhamer, Peter G.L.; Leiss, Kirsten A.

2017-01-01

Plant defenses inducible by herbivorous arthropods can determine performance of subsequent feeding herbivores. We investigated how infestation of tomato (Solanum lycopersicum) plants with the Western flower thrips (Frankliniella occidentalis) alters host plant suitability and foraging decisions of their conspecifics. We explored the role of delayed-induced jasmonic acid (JA)-mediated plant defense responses in thrips preference by using the tomato mutant def-1, impaired in JA biosynthesis. In particular, we investigated the effect of thrips infestation on trichome-associated tomato defenses. The results showed that when offered a choice, thrips preferred non-infested plants over infested wild-type plants, while no differences were observed in def-1. Exogenous application of methyl jasmonate restored the repellency effect in def-1. Gene expression analysis showed induction of the JA defense signaling pathway in wild-type plants, while activating the ethylene signaling pathway in both genotypes. Activation of JA defenses led to increases in type-VI leaf glandular trichome densities in the wild type, augmenting the production of trichome-associated volatiles, i.e. terpenes. Our study revealed that plant-mediated intraspecific interactions between thrips are determined by JA-mediated defenses in tomato. We report that insects can alter not only trichome densities but also the allelochemicals produced therein, and that this response might depend on the magnitude and/or type of the induction. PMID:28158865

Determination of Highly Sensitive Biological Cell Model Systems to Screen BPA-Related Health Hazards Using Pathway Studio.

PubMed

Ryu, Do-Yeal; Rahman, Md Saidur; Pang, Myung-Geol

2017-09-06

Bisphenol-A (BPA) is a ubiquitous endocrine-disrupting chemical. Recently, many issues have arisen surrounding the disease pathogenesis of BPA. Therefore, several studies have been conducted to investigate the proteomic biomarkers of BPA that are associated with disease processes. However, studies on identifying highly sensitive biological cell model systems in determining BPA health risk are lacking. Here, we determined suitable cell model systems and potential biomarkers for predicting BPA-mediated disease using the bioinformatics tool Pathway Studio. We compiled known BPA-mediated diseases in humans, which were categorized into five major types. Subsequently, we investigated the differentially expressed proteins following BPA exposure in several cell types, and analyzed the efficacy of altered proteins to investigate their associations with BPA-mediated diseases. Our results demonstrated that colon cancer cells (SW480), mammary gland, and Sertoli cells were highly sensitive biological model systems, because of the efficacy of predicting the majority of BPA-mediated diseases. We selected glucose-6-phosphate dehydrogenase (G6PD), cytochrome b-c1 complex subunit 1 (UQCRC1), and voltage-dependent anion-selective channel protein 2 (VDAC2) as highly sensitive biomarkers to predict BPA-mediated diseases. Furthermore, we summarized proteomic studies in spermatozoa following BPA exposure, which have recently been considered as another suitable cell type for predicting BPA-mediated diseases.

Determination of Highly Sensitive Biological Cell Model Systems to Screen BPA-Related Health Hazards Using Pathway Studio

PubMed Central

Ryu, Do-Yeal

2017-01-01

Bisphenol-A (BPA) is a ubiquitous endocrine-disrupting chemical. Recently, many issues have arisen surrounding the disease pathogenesis of BPA. Therefore, several studies have been conducted to investigate the proteomic biomarkers of BPA that are associated with disease processes. However, studies on identifying highly sensitive biological cell model systems in determining BPA health risk are lacking. Here, we determined suitable cell model systems and potential biomarkers for predicting BPA-mediated disease using the bioinformatics tool Pathway Studio. We compiled known BPA-mediated diseases in humans, which were categorized into five major types. Subsequently, we investigated the differentially expressed proteins following BPA exposure in several cell types, and analyzed the efficacy of altered proteins to investigate their associations with BPA-mediated diseases. Our results demonstrated that colon cancer cells (SW480), mammary gland, and Sertoli cells were highly sensitive biological model systems, because of the efficacy of predicting the majority of BPA-mediated diseases. We selected glucose-6-phosphate dehydrogenase (G6PD), cytochrome b-c1 complex subunit 1 (UQCRC1), and voltage-dependent anion-selective channel protein 2 (VDAC2) as highly sensitive biomarkers to predict BPA-mediated diseases. Furthermore, we summarized proteomic studies in spermatozoa following BPA exposure, which have recently been considered as another suitable cell type for predicting BPA-mediated diseases. PMID:28878155

Climate change, wine, and conservation.

PubMed

Hannah, Lee; Roehrdanz, Patrick R; Ikegami, Makihiko; Shepard, Anderson V; Shaw, M Rebecca; Tabor, Gary; Zhi, Lu; Marquet, Pablo A; Hijmans, Robert J

2013-04-23

Climate change is expected to impact ecosystems directly, such as through shifting climatic controls on species ranges, and indirectly, for example through changes in human land use that may result in habitat loss. Shifting patterns of agricultural production in response to climate change have received little attention as a potential impact pathway for ecosystems. Wine grape production provides a good test case for measuring indirect impacts mediated by changes in agriculture, because viticulture is sensitive to climate and is concentrated in Mediterranean climate regions that are global biodiversity hotspots. Here we demonstrate that, on a global scale, the impacts of climate change on viticultural suitability are substantial, leading to possible conservation conflicts in land use and freshwater ecosystems. Area suitable for viticulture decreases 25% to 73% in major wine producing regions by 2050 in the higher RCP 8.5 concentration pathway and 19% to 62% in the lower RCP 4.5. Climate change may cause establishment of vineyards at higher elevations that will increase impacts on upland ecosystems and may lead to conversion of natural vegetation as production shifts to higher latitudes in areas such as western North America. Attempts to maintain wine grape productivity and quality in the face of warming may be associated with increased water use for irrigation and to cool grapes through misting or sprinkling, creating potential for freshwater conservation impacts. Agricultural adaptation and conservation efforts are needed that anticipate these multiple possible indirect effects.

Climate change, wine, and conservation

PubMed Central

Hannah, Lee; Roehrdanz, Patrick R.; Ikegami, Makihiko; Shepard, Anderson V.; Shaw, M. Rebecca; Tabor, Gary; Zhi, Lu; Marquet, Pablo A.; Hijmans, Robert J.

2013-01-01

Climate change is expected to impact ecosystems directly, such as through shifting climatic controls on species ranges, and indirectly, for example through changes in human land use that may result in habitat loss. Shifting patterns of agricultural production in response to climate change have received little attention as a potential impact pathway for ecosystems. Wine grape production provides a good test case for measuring indirect impacts mediated by changes in agriculture, because viticulture is sensitive to climate and is concentrated in Mediterranean climate regions that are global biodiversity hotspots. Here we demonstrate that, on a global scale, the impacts of climate change on viticultural suitability are substantial, leading to possible conservation conflicts in land use and freshwater ecosystems. Area suitable for viticulture decreases 25% to 73% in major wine producing regions by 2050 in the higher RCP 8.5 concentration pathway and 19% to 62% in the lower RCP 4.5. Climate change may cause establishment of vineyards at higher elevations that will increase impacts on upland ecosystems and may lead to conversion of natural vegetation as production shifts to higher latitudes in areas such as western North America. Attempts to maintain wine grape productivity and quality in the face of warming may be associated with increased water use for irrigation and to cool grapes through misting or sprinkling, creating potential for freshwater conservation impacts. Agricultural adaptation and conservation efforts are needed that anticipate these multiple possible indirect effects. PMID:23569231

Climate envelope predictions indicate an enlarged suitable wintering distribution for Great Bustards (Otis tarda dybowskii) in China for the 21st century

PubMed Central

Mi, Chunrong; Falk, Huettmann

2016-01-01

The rapidly changing climate makes humans realize that there is a critical need to incorporate climate change adaptation into conservation planning. Whether the wintering habitats of Great Bustards (Otis tarda dybowskii), a globally endangered migratory subspecies whose population is approximately 1,500–2,200 individuals in China, would be still suitable in a changing climate environment, and where this could be found, is an important protection issue. In this study, we selected the most suitable species distribution model for bustards using climate envelopes from four machine learning models, combining two modelling approaches (TreeNet and Random Forest) with two sets of variables (correlated variables removed or not). We used common evaluation methods area under the receiver operating characteristic curves (AUC) and the True Skill Statistic (TSS) as well as independent test data to identify the most suitable model. As often found elsewhere, we found Random Forest with all environmental variables outperformed in all assessment methods. When we projected the best model to the latest IPCC-CMIP5 climate scenarios (Representative Concentration Pathways (RCPs) 2.6, 4.5 and 8.5 in three Global Circulation Models (GCMs)), and averaged the project results of the three models, we found that suitable wintering habitats in the current bustard distribution would increase during the 21st century. The Northeast Plain and the south of North China were projected to become two major wintering areas for bustards. However, the models suggest that some currently suitable habitats will experience a reduction, such as Dongting Lake and Poyang Lake in the Middle and Lower Yangtze River Basin. Although our results suggested that suitable habitats in China would widen with climate change, greater efforts should be undertaken to assess and mitigate unstudied human disturbance, such as pollution, hunting, agricultural development, infrastructure construction, habitat fragmentation, and oil and mine exploitation. All of these are negatively and intensely linked with global change. PMID:26855870

Climate envelope predictions indicate an enlarged suitable wintering distribution for Great Bustards (Otis tarda dybowskii) in China for the 21st century.

PubMed

Mi, Chunrong; Falk, Huettmann; Guo, Yumin

2016-01-01

The rapidly changing climate makes humans realize that there is a critical need to incorporate climate change adaptation into conservation planning. Whether the wintering habitats of Great Bustards (Otis tarda dybowskii), a globally endangered migratory subspecies whose population is approximately 1,500-2,200 individuals in China, would be still suitable in a changing climate environment, and where this could be found, is an important protection issue. In this study, we selected the most suitable species distribution model for bustards using climate envelopes from four machine learning models, combining two modelling approaches (TreeNet and Random Forest) with two sets of variables (correlated variables removed or not). We used common evaluation methods area under the receiver operating characteristic curves (AUC) and the True Skill Statistic (TSS) as well as independent test data to identify the most suitable model. As often found elsewhere, we found Random Forest with all environmental variables outperformed in all assessment methods. When we projected the best model to the latest IPCC-CMIP5 climate scenarios (Representative Concentration Pathways (RCPs) 2.6, 4.5 and 8.5 in three Global Circulation Models (GCMs)), and averaged the project results of the three models, we found that suitable wintering habitats in the current bustard distribution would increase during the 21st century. The Northeast Plain and the south of North China were projected to become two major wintering areas for bustards. However, the models suggest that some currently suitable habitats will experience a reduction, such as Dongting Lake and Poyang Lake in the Middle and Lower Yangtze River Basin. Although our results suggested that suitable habitats in China would widen with climate change, greater efforts should be undertaken to assess and mitigate unstudied human disturbance, such as pollution, hunting, agricultural development, infrastructure construction, habitat fragmentation, and oil and mine exploitation. All of these are negatively and intensely linked with global change.

Deregulation of the COP9 signalosome-cullin-RING ubiquitin-ligase pathway: mechanisms and roles in urological cancers.

PubMed

Gummlich, Linda; Rabien, Anja; Jung, Klaus; Dubiel, Wolfgang

2013-07-01

The COP9 signalosome (CSN)-cullin-RING ubiquitin (Ub)-ligase (CRL) pathway is a prominent segment of the Ub proteasome system (UPS). It specifically ubiquitinates proteins and targets them for proteolytic elimination. As part of the UPS it maintains essential cellular processes including cell cycle progression, DNA repair, antigen processing and signal transduction. The CSN-CRL pathway consists of the CSN possessing eight subunits (CSN1-CSN8) and one CRL consisting of a cullin, a RING-domain protein and a substrate recognition subunit (SRS). In human cells approximately 250 CRLs exist each of which interacting with a specific set of substrates and the CSN. The CSN-CRL interplay determines the activity and specificity of CRL ubiquitination. The removal of the Ub-like protein Nedd8 from the CRL component cullin by the CSN (deneddylation) reduces the ubiquitinating activity and at the same time enables reassembly of CRLs in order to adapt to substrate specificity requirements. On the other hand, CRLs as well as substrates negatively influence the deneddylating activity of the CSN. In recent years evidence accumulated that deregulation of the CSN-CRL pathway can cause cancer. Here we review current knowledge on modifications of CSN and CRL components including CSN subunits, SRSs and cullins causing tumorigenesis with emphasis on urological neoplasia. The CSN-CRL pathway is a target of tumor-viruses as well as of a multitude of miRNAs. Recently evaluated miRNAs altered in urological cancers might have impact on the CSN-CRL pathway which has to be analyzed in future experiments. We propose that the pathway is a suitable target for future tumor therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Reconstruction of the High-Osmolarity Glycerol (HOG) Signaling Pathway from the Halophilic Fungus Wallemia ichthyophaga in Saccharomyces cerevisiae.

PubMed

Konte, Tilen; Terpitz, Ulrich; Plemenitaš, Ana

2016-01-01

The basidiomycetous fungus Wallemia ichthyophaga grows between 1.7 and 5.1 M NaCl and is the most halophilic eukaryote described to date. Like other fungi, W. ichthyophaga detects changes in environmental salinity mainly by the evolutionarily conserved high-osmolarity glycerol (HOG) signaling pathway. In Saccharomyces cerevisiae, the HOG pathway has been extensively studied in connection to osmotic regulation, with a valuable knock-out strain collection established. In the present study, we reconstructed the architecture of the HOG pathway of W. ichthyophaga in suitable S. cerevisiae knock-out strains, through heterologous expression of the W. ichthyophaga HOG pathway proteins. Compared to S. cerevisiae, where the Pbs2 (ScPbs2) kinase of the HOG pathway is activated via the SHO1 and SLN1 branches, the interactions between the W. ichthyophaga Pbs2 (WiPbs2) kinase and the W. ichthyophaga SHO1 branch orthologs are not conserved: as well as evidence of poor interactions between the WiSho1 Src-homology 3 (SH3) domain and the WiPbs2 proline-rich motif, the absence of a considerable part of the osmosensing apparatus in the genome of W. ichthyophaga suggests that the SHO1 branch components are not involved in HOG signaling in this halophilic fungus. In contrast, the conserved activation of WiPbs2 by the S. cerevisiae ScSsk2/ScSsk22 kinase and the sensitivity of W. ichthyophaga cells to fludioxonil, emphasize the significance of two-component (SLN1-like) signaling via Group III histidine kinase. Combined with protein modeling data, our study reveals conserved and non-conserved protein interactions in the HOG signaling pathway of W. ichthyophaga and therefore significantly improves the knowledge of hyperosmotic signal processing in this halophilic fungus.

HBVPathDB: a database of HBV infection-related molecular interaction network.

PubMed

Zhang, Yi; Bo, Xiao-Chen; Yang, Jing; Wang, Sheng-Qi

2005-03-21

To describe molecules or genes interaction between hepatitis B viruses (HBV) and host, for understanding how virus' and host's genes and molecules are networked to form a biological system and for perceiving mechanism of HBV infection. The knowledge of HBV infection-related reactions was organized into various kinds of pathways with carefully drawn graphs in HBVPathDB. Pathway information is stored with relational database management system (DBMS), which is currently the most efficient way to manage large amounts of data and query is implemented with powerful Structured Query Language (SQL). The search engine is written using Personal Home Page (PHP) with SQL embedded and web retrieval interface is developed for searching with Hypertext Markup Language (HTML). We present the first version of HBVPathDB, which is a HBV infection-related molecular interaction network database composed of 306 pathways with 1 050 molecules involved. With carefully drawn graphs, pathway information stored in HBVPathDB can be browsed in an intuitive way. We develop an easy-to-use interface for flexible accesses to the details of database. Convenient software is implemented to query and browse the pathway information of HBVPathDB. Four search page layout options-category search, gene search, description search, unitized search-are supported by the search engine of the database. The database is freely available at http://www.bio-inf.net/HBVPathDB/HBV/. The conventional perspective HBVPathDB have already contained a considerable amount of pathway information with HBV infection related, which is suitable for in-depth analysis of molecular interaction network of virus and host. HBVPathDB integrates pathway data-sets with convenient software for query, browsing, visualization, that provides users more opportunity to identify regulatory key molecules as potential drug targets and to explore the possible mechanism of HBV infection based on gene expression datasets.

Systematic reconstruction of TRANSPATH data into Cell System Markup Language

PubMed Central

Nagasaki, Masao; Saito, Ayumu; Li, Chen; Jeong, Euna; Miyano, Satoru

2008-01-01

Background Many biological repositories store information based on experimental study of the biological processes within a cell, such as protein-protein interactions, metabolic pathways, signal transduction pathways, or regulations of transcription factors and miRNA. Unfortunately, it is difficult to directly use such information when generating simulation-based models. Thus, modeling rules for encoding biological knowledge into system-dynamics-oriented standardized formats would be very useful for fully understanding cellular dynamics at the system level. Results We selected the TRANSPATH database, a manually curated high-quality pathway database, which provides a plentiful source of cellular events in humans, mice, and rats, collected from over 31,500 publications. In this work, we have developed 16 modeling rules based on hybrid functional Petri net with extension (HFPNe), which is suitable for graphical representing and simulating biological processes. In the modeling rules, each Petri net element is incorporated with Cell System Ontology to enable semantic interoperability of models. As a formal ontology for biological pathway modeling with dynamics, CSO also defines biological terminology and corresponding icons. By combining HFPNe with the CSO features, it is possible to make TRANSPATH data to simulation-based and semantically valid models. The results are encoded into a biological pathway format, Cell System Markup Language (CSML), which eases the exchange and integration of biological data and models. Conclusion By using the 16 modeling rules, 97% of the reactions in TRANSPATH are converted into simulation-based models represented in CSML. This reconstruction demonstrates that it is possible to use our rules to generate quantitative models from static pathway descriptions. PMID:18570683

Systematic reconstruction of TRANSPATH data into cell system markup language.

PubMed

Nagasaki, Masao; Saito, Ayumu; Li, Chen; Jeong, Euna; Miyano, Satoru

2008-06-23

Many biological repositories store information based on experimental study of the biological processes within a cell, such as protein-protein interactions, metabolic pathways, signal transduction pathways, or regulations of transcription factors and miRNA. Unfortunately, it is difficult to directly use such information when generating simulation-based models. Thus, modeling rules for encoding biological knowledge into system-dynamics-oriented standardized formats would be very useful for fully understanding cellular dynamics at the system level. We selected the TRANSPATH database, a manually curated high-quality pathway database, which provides a plentiful source of cellular events in humans, mice, and rats, collected from over 31,500 publications. In this work, we have developed 16 modeling rules based on hybrid functional Petri net with extension (HFPNe), which is suitable for graphical representing and simulating biological processes. In the modeling rules, each Petri net element is incorporated with Cell System Ontology to enable semantic interoperability of models. As a formal ontology for biological pathway modeling with dynamics, CSO also defines biological terminology and corresponding icons. By combining HFPNe with the CSO features, it is possible to make TRANSPATH data to simulation-based and semantically valid models. The results are encoded into a biological pathway format, Cell System Markup Language (CSML), which eases the exchange and integration of biological data and models. By using the 16 modeling rules, 97% of the reactions in TRANSPATH are converted into simulation-based models represented in CSML. This reconstruction demonstrates that it is possible to use our rules to generate quantitative models from static pathway descriptions.

The integrated effect of moderate exercise on coronary heart disease.

PubMed

Mathews, Marc J; Mathews, Edward H; Mathews, George E

Moderate exercise is associated with a lower risk for coronary heart disease (CHD). A suitable integrated model of the CHD pathogenetic pathways relevant to moderate exercise may help to elucidate this association. Such a model is currently not available in the literature. An integrated model of CHD was developed and used to investigate pathogenetic pathways of importance between exercise and CHD. Using biomarker relative-risk data, the pathogenetic effects are representable as measurable effects based on changes in biomarkers. The integrated model provides insight into higherorder interactions underlying the associations between CHD and moderate exercise. A novel 'connection graph' was developed, which simplifies these interactions. It quantitatively illustrates the relationship between moderate exercise and various serological biomarkers of CHD. The connection graph of moderate exercise elucidates all the possible integrated actions through which risk reduction may occur. An integrated model of CHD provides a summary of the effects of moderate exercise on CHD. It also shows the importance of each CHD pathway that moderate exercise influences. The CHD risk-reducing effects of exercise appear to be primarily driven by decreased inflammation and altered metabolism.

Understanding bistability in yeast glycolysis using general properties of metabolic pathways.

PubMed

Planqué, Robert; Bruggeman, Frank J; Teusink, Bas; Hulshof, Josephus

2014-09-01

Glycolysis is the central pathway in energy metabolism in the majority of organisms. In a recent paper, van Heerden et al. showed experimentally and computationally that glycolysis can exist in two states, a global steady state and a so-called imbalanced state. In the imbalanced state, intermediary metabolites accumulate at low levels of ATP and inorganic phosphate. It was shown that Baker's yeast uses a peculiar regulatory mechanism--via trehalose metabolism--to ensure that most yeast cells reach the steady state and not the imbalanced state. Here we explore the apparent bistable behaviour in a core model of glycolysis that is based on a well-established detailed model, and study in great detail the bifurcation behaviour of solutions, without using any numerical information on parameter values. We uncover a rich suite of solutions, including so-called imbalanced states, bistability, and oscillatory behaviour. The techniques employed are generic, directly suitable for a wide class of biochemical pathways, and could lead to better analytical treatments of more detailed models. Copyright © 2014 Elsevier Inc. All rights reserved.

Utilization of biodiesel by-product as substrate for high-production of β-farnesene via relatively balanced mevalonate pathway in Escherichia coli.

PubMed

You, Shengping; Yin, Qingdian; Zhang, Jianye; Zhang, Chengyu; Qi, Wei; Gao, Lan; Tao, Zhiping; Su, Rongxin; He, Zhimin

2017-11-01

Farnesene has been identified as suitable jet fuel substitutes and metabolic engineering for microbial production of farnesene is an alternative and attractive route. In this study, due to accumulation of toxic intermediate isopentenyl pyrophosphate (IPP), an engineered Escherichia coli strain harboring heterologous mevalonate pathway produced only 4.11mg/L β-farnesene. Through higher-level expression of isopentenyl diphosphate isomerase and farnesyl diphosphate synthase to minimize the accumulated IPP, another engineered strain with relatively balanced mevalonate pathway was constructed and had the highest production of β-farnesene to date (8.74g/L) by Escherichia coli in a lab bioreactor. Furthermore, this is the first report on utilization of biodiesel by-product (simple purification) as substrate for high-production of β-farnesene by the engineered strain optimized and β-farnesene concentration reached 2.83g/L in a lab bioreactor. Therefore, the engineered strain optimized could be used as a platform host for high-production of other terpenoids using biodiesel by-product as substrate. Copyright © 2017 Elsevier Ltd. All rights reserved.

Unexpected role of the IMD pathway in Drosophila gut defense against Staphylococcus aureus.

PubMed

Hori, Aki; Kurata, Shoichiro; Kuraishi, Takayuki

2018-01-01

In this study, fruit fly of the genus Drosophila is utilized as a suitable model animal to investigate the molecular mechanisms of innate immunity. To combat orally transmitted pathogenic Gram-negative bacteria, the Drosophila gut is armed with the peritrophic matrix, which is a physical barrier composed of chitin and glycoproteins: the Duox system that produces reactive oxygen species (ROS), which in turn sterilize infected microbes, and the IMD pathway that regulates the expression of antimicrobial peptides (AMPs), which in turn control ROS-resistant pathogens. However, little is known about the defense mechanisms against Gram-positive bacteria in the fly gut. Here, we show that the peritrophic matrix protects Drosophila against Gram-positive bacteria S. aureus. We also define the few roles of ROS in response to the infection and show that the IMD pathway is required for the clearance of ingested microbes, possibly independently from AMP expression. These findings provide a new aspect of the gut defense system of Drosophila, and helps to elucidate the processes of gut-microbe symbiosis and pathogenesis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

More arrows in the quiver: new pathways and old problems with heavy alkaline earth metal diphenylmethanides.

PubMed

Alexander, Jacob S; Ruhlandt-Senge, Karin

2004-03-05

Progress in the field of sigma-bonded alkaline earth organometallics has been handicapped by numerous complications, such as high reactivity, low solubility, and the limited availability of suitable starting materials. Here we present two synthetic methods, hydrocarbon elimination and desilylation, as alternative routes into this chemistry. A novel barium diphenylmethanide was prepared using these routes delineating that both methods provide a powerful, versatile synthetic access route to an extended library of organometallic alkaline earth derivatives.

Proceedings of the Workshop on Flight Testing to Identify Pilot Workload and Pilot Dynamics Held at the Edwards AFB, California on 19-21 January 1982

DTIC Science & Technology

1982-05-01

precognitive stages or, in other words, a *Adaptation changes strategy and performance in a new environment, whereas learning or skill development changes...expect the pursuit level of operation to have a lower PML than the compen- satory stage.. 3. Final stage ( precognitive control). At this level of skill...in degraded system performance, if not failure. The compensatory-pursuit- precognitive pathways structure is suitable to represent not only a pilot or

Photoluminescence properties of non-stoichiometric strontium zirconate powder phosphor

NASA Astrophysics Data System (ADS)

Jarý, V.; Boháček, P.; Mihóková, E.; Havlák, L.; Trunda, B.; Nikl, M.

2013-03-01

Excitation and emission spectra and decay kinetics of non-stoichiometric strontium zirconate powder phosphor were measured in the 8-500 K temperature interval. Phenomenological model was applied to extract quantitative parameters of the excited state levels and nonradiative quenching pathways related to the luminescence centre. Delayed recombination integrals measurement was employed to investigate the occurrence of thermally induced ionization of the excited state of the emission centre. The nature of the emission centre itself is suggested. Suitability for phosphor and scintillation application is discussed.

Combined "de novo" and "ex novo" lipid fermentation in a mix-medium of corncob acid hydrolysate and soybean oil by Trichosporon dermatis.

PubMed

Huang, Chao; Luo, Mu-Tan; Chen, Xue-Fang; Qi, Gao-Xiang; Xiong, Lian; Lin, Xiao-Qing; Wang, Can; Li, Hai-Long; Chen, Xin-De

2017-01-01

Microbial oil is one important bio-product for its important function in energy, chemical, and food industry. Finding suitable substrates is one key issue for its industrial application. Both hydrophilic and hydrophobic substrates can be utilized by oleaginous microorganisms with two different bio-pathways (" de novo " lipid fermentation and " ex novo " lipid fermentation). To date, most of the research on lipid fermentation has focused mainly on only one fermentation pathway and little work was carried out on both " de novo " and " ex novo " lipid fermentation simultaneously; thus, the advantages of both lipid fermentation cannot be fulfilled comprehensively. In this study, corncob acid hydrolysate with soybean oil was used as a mix-medium for combined " de novo " and " ex novo " lipid fermentation by oleaginous yeast Trichosporon dermatis . Both hydrophilic and hydrophobic substrates (sugars and soybean oil) in the medium can be utilized simultaneously and efficiently by T. dermatis . Different fermentation modes were compared and the batch mode was the most suitable for the combined fermentation. The influence of soybean oil concentration, inoculum size, and initial pH on the lipid fermentation was evaluated and 20 g/L soybean oil, 5% inoculum size, and initial pH 6.0 were suitable for this bioprocess. By this technology, the lipid composition of extracellular hydrophobic substrate (soybean oil) can be modified. Although adding emulsifier showed little beneficial effect on lipid production, it can modify the intracellular lipid composition of T. dermatis . The present study proves the potential and possibility of combined " de novo " and " ex novo " lipid fermentation. This technology can use hydrophilic and hydrophobic sustainable bio-resources to generate lipid feedstock for the production of biodiesel or other lipid-based chemical compounds and to treat some special wastes such as oil-containing wastewater.

Specific recommendations for accurate and direct use of PET-CT in PET guided radiotherapy for head and neck sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomas, C. M., E-mail: christopher.thomas@gstt.nhs.uk; Convery, D. J.; Greener, A. G.

2014-04-15

Purpose: To provide specific experience-based guidance and recommendations for centers wishing to develop, validate, and implement an accurate and efficient process for directly using positron emission tomography-computed tomography (PET-CT) for the radiotherapy planning of head and neck cancer patients. Methods: A PET-CT system was modified with hard-top couch, external lasers and radiotherapy immobilization and indexing devices and was subject to a commissioning and quality assurance program. PET-CT imaging protocols were developed specifically for radiotherapy planning and the image quality and pathway tested using phantoms and five patients recruited into an in-house study. Security and accuracy of data transfer was testedmore » throughout the whole data pathway. The patient pathway was fully established and tested ready for implementation in a PET-guided dose-escalation trial for head and neck cancer patients. Results: Couch deflection was greater than for departmental CT simulator machines. An area of high attenuation in the couch generated image artifacts and adjustments were made accordingly. Using newly developed protocols CT image quality was suitable to maintain delineation and treatment accuracy. Upon transfer of data to the treatment planning system a half pixel offset between PET and CT was observed and corrected. By taking this into account, PET to CT alignment accuracy was maintained below 1 mm in all systems in the data pathway. Transfer of structures delineated in the PET fusion software to the radiotherapy treatment planning system was validated. Conclusions: A method to perform direct PET-guided radiotherapy planning was successfully validated and specific recommendations were developed to assist other centers. Of major concern is ensuring that the quality of PET and CT data is appropriate for radiotherapy treatment planning and on-treatment verification. Couch movements can be compromised, bore-size can be a limitation for certain immobilization techniques, laser positioning may affect setup accuracy and couch deflection may be greater than scanners dedicated to radiotherapy. The full set of departmental commissioning and routine quality assurance tests applied to radiotherapy CT simulators must be carried out on the PET-CT scanner. CT image quality must be optimized for radiotherapy planning whilst understanding that the appearance will differ between scanners and may affect delineation. PET-CT quality assurance schedules will need to be added to and modified to incorporate radiotherapy quality assurance. Methods of working for radiotherapy and PET staff will change to take into account considerations of both parties. PET to CT alignment must be subject to quality control on a loaded and unloaded couch preferably using a suitable emission phantom, and tested throughout the whole data pathway. Data integrity must be tested throughout the whole pathway and a system included to verify that delineated structures are transferred correctly. Excellent multidisciplinary team communication and working is vital, and key staff members on both sides should be specifically dedicated to the project. Patient pathway should be clearly devised to optimize patient care and the resources of all departments. Recruitment of a cohort of patients into a methodology study is valuable to test the quality assurance methods and pathway.« less

Safe and sustainable increases in day case emergency surgery.

PubMed

Hotchen, Andrew J; Coleman, Grant; O'Callaghan, John M; McWhinnie, Doug

2016-03-01

Selected patients referred to emergency general surgery departments are suitable for day case emergency surgery with no overnight hospital stay. There are no well-described sustainable pathways for these expedited operations and in many hospitals patients undergo unnecessary admissions and experience long waiting times. The authors proposed a new, sustainable, day case emergency surgery pathway which was implemented to streamline the assessment, treatment and discharge of acute surgical referrals. It requires rapid assessment of the patient by a senior clinician, and ready availability of diagnostic services and operating facilities. To assess this pathway, the authors conducted a prospective audit of general surgical referrals to a district general hospital in the UK. During the inclusion period 746 emergency referrals were assessed, 281 (37%) of these underwent an operation. Over a 5-month investigation period, the audit found that approximately 27% of all emergency general surgery patients requiring an operation could be managed with day case emergency surgery. This figure was maintained throughout the duration of the study. Operations included incision and drainage of abscesses, incarcerated hernia repairs and appendicectomies. The average length of stay of all surgical admissions decreased from 5 days to less than 3 days and the median time to senior review was 30 minutes. The authors have developed a pathway involving permanent members of the surgical assessment team that is sustainable over a 5-month period. The pathway has allowed rapid assessment of patients and reduced unnecessary inpatient stay in a sustainable and reproducible manner.

Reaction pathways for the deoxygenation of vegetable oils and related model compounds.

PubMed

Gosselink, Robert W; Hollak, Stefan A W; Chang, Shu-Wei; van Haveren, Jacco; de Jong, Krijn P; Bitter, Johannes H; van Es, Daan S

2013-09-01

Vegetable oil-based feeds are regarded as an alternative source for the production of fuels and chemicals. Paraffins and olefins can be produced from these feeds through catalytic deoxygenation. The fundamentals of this process are mostly studied by using model compounds such as fatty acids, fatty acid esters, and specific triglycerides because of their structural similarity to vegetable oils. In this Review we discuss the impact of feedstock, reaction conditions, and nature of the catalyst on the reaction pathways of the deoxygenation of vegetable oils and its derivatives. As such, we conclude on the suitability of model compounds for this reaction. It is shown that the type of catalyst has a significant effect on the deoxygenation pathway, that is, group 10 metal catalysts are active in decarbonylation/decarboxylation whereas metal sulfide catalysts are more selective to hydrodeoxygenation. Deoxygenation studies performed under H2 showed similar pathways for fatty acids, fatty acid esters, triglycerides, and vegetable oils, as mostly deoxygenation occurs indirectly via the formation of fatty acids. Deoxygenation in the absence of H2 results in significant differences in reaction pathways and selectivities depending on the feedstock. Additionally, using unsaturated feedstocks under inert gas results in a high selectivity to undesired reactions such as cracking and the formation of heavies. Therefore, addition of H2 is proposed to be essential for the catalytic deoxygenation of vegetable oil feeds. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pathway-based identification of biomarkers for targeted therapeutics: personalized oncology with PI3K pathway inhibitors.

PubMed

Andersen, Jannik N; Sathyanarayanan, Sriram; Di Bacco, Alessandra; Chi, An; Zhang, Theresa; Chen, Albert H; Dolinski, Brian; Kraus, Manfred; Roberts, Brian; Arthur, William; Klinghoffer, Rich A; Gargano, Diana; Li, Lixia; Feldman, Igor; Lynch, Bethany; Rush, John; Hendrickson, Ronald C; Blume-Jensen, Peter; Paweletz, Cloud P

2010-08-04

Although we have made great progress in understanding the complex genetic alterations that underlie human cancer, it has proven difficult to identify which molecularly targeted therapeutics will benefit which patients. Drug-specific modulation of oncogenic signaling pathways in specific patient subpopulations can predict responsiveness to targeted therapy. Here, we report a pathway-based phosphoprofiling approach to identify and quantify clinically relevant, drug-specific biomarkers for phosphatidylinositol 3-kinase (PI3K) pathway inhibitors that target AKT, phosphoinositide-dependent kinase 1 (PDK1), and PI3K-mammalian target of rapamycin (mTOR). We quantified 375 nonredundant PI3K pathway-relevant phosphopeptides, all containing AKT, PDK1, or mitogen-activated protein kinase substrate recognition motifs. Of these phosphopeptides, 71 were drug-regulated, 11 of them by all three inhibitors. Drug-modulated phosphoproteins were enriched for involvement in cytoskeletal reorganization (filamin, stathmin, dynamin, PAK4, and PTPN14), vesicle transport (LARP1, VPS13D, and SLC20A1), and protein translation (S6RP and PRAS40). We then generated phosphospecific antibodies against selected, drug-regulated phosphorylation sites that would be suitable as biomarker tools for PI3K pathway inhibitors. As proof of concept, we show clinical translation feasibility for an antibody against phospho-PRAS40(Thr246). Evaluation of binding of this antibody in human cancer cell lines, a PTEN (phosphatase and tensin homolog deleted from chromosome 10)-deficient mouse prostate tumor model, and triple-negative breast tumor tissues showed that phospho-PRAS40(Thr246) positively correlates with PI3K pathway activation and predicts AKT inhibitor sensitivity. In contrast to phosphorylation of AKT(Thr308), the phospho-PRAS40(Thr246) epitope is highly stable in tissue samples and thus is ideal for immunohistochemistry. In summary, our study illustrates a rational approach for discovery of drug-specific biomarkers toward development of patient-tailored treatments.

Suitable Days for Plant Growth Disappear under Projected Climate Change: Potential Human and Biotic Vulnerability

PubMed Central

Mora, Camilo; Caldwell, Iain R.; Caldwell, Jamie M.; Fisher, Micah R.; Genco, Brandon M.; Running, Steven W.

2015-01-01

Ongoing climate change can alter conditions for plant growth, in turn affecting ecological and social systems. While there have been considerable advances in understanding the physical aspects of climate change, comprehensive analyses integrating climate, biological, and social sciences are less common. Here we use climate projections under alternative mitigation scenarios to show how changes in environmental variables that limit plant growth could impact ecosystems and people. We show that although the global mean number of days above freezing will increase by up to 7% by 2100 under “business as usual” (representative concentration pathway [RCP] 8.5), suitable growing days will actually decrease globally by up to 11% when other climatic variables that limit plant growth are considered (i.e., temperature, water availability, and solar radiation). Areas in Russia, China, and Canada are projected to gain suitable plant growing days, but the rest of the world will experience losses. Notably, tropical areas could lose up to 200 suitable plant growing days per year. These changes will impact most of the world’s terrestrial ecosystems, potentially triggering climate feedbacks. Human populations will also be affected, with up to ~2,100 million of the poorest people in the world (~30% of the world’s population) highly vulnerable to changes in the supply of plant-related goods and services. These impacts will be spatially variable, indicating regions where adaptations will be necessary. Changes in suitable plant growing days are projected to be less severe under strong and moderate mitigation scenarios (i.e., RCP 2.6 and RCP 4.5), underscoring the importance of reducing emissions to avoid such disproportionate impacts on ecosystems and people. PMID:26061091

Present and Future Projections of Habitat Suitability of the Asian Tiger Mosquito, a Vector of Viral Pathogens, from Global Climate Simulations.

NASA Astrophysics Data System (ADS)

Proestos, Y.; Christophides, G.; Erguler, K.; Tanarhte, M.; Waldock, J.; Lelieveld, J.

2014-12-01

Climate change can influence the transmission of vector borne diseases (VBDs) through altering the habitat suitability of insect vectors. Here we present global climate model simulations and evaluate the associated uncertainties in view of the main meteorological factors that may affect the distribution of the Asian Tiger mosquito (Aedes albopictus), which can transmit pathogens that cause Chikungunya, Dengue fever, yellow fever and various encephalitides. Using a general circulation model (GCM) at 50 km horizontal resolution to simulate mosquito survival variables including temperature, precipitation and relative humidity, we present both global and regional projections of the habitat suitability up to the middle of the 21st century. The model resolution of 50 km allows evaluation against previous projections for Europe and provides a basis for comparative analyses with other regions. Model uncertainties and performance are addressed in light of the recent CMIP5 ensemble climate model simulations for the RCP8.5 concentration pathway and using meteorological re-analysis data (ERA-Interim/ECMWF) for the recent past. Uncertainty ranges associated with the thresholds of meteorological variables that may affect the distribution of Ae. albopictus are diagnosed using fuzzy-logic methodology, notably to assess the influence of selected meteorological criteria and combinations of criteria that influence mosquito habitat suitability. From the climate projections for 2050, and adopting a habitat suitability index larger than 70%, we estimate that about 2.4 billion individuals in a land area of nearly 20 million square kilometres will potentially be exposed to Ae. albopictus. The synthesis of fuzzy-logic based on mosquito biology and climate change analysis provides new insights into the regional and global spreading of VBDs to support disease control and policy making.

Suitable Days for Plant Growth Disappear under Projected Climate Change: Potential Human and Biotic Vulnerability.

PubMed

Mora, Camilo; Caldwell, Iain R; Caldwell, Jamie M; Fisher, Micah R; Genco, Brandon M; Running, Steven W

2015-06-01

Ongoing climate change can alter conditions for plant growth, in turn affecting ecological and social systems. While there have been considerable advances in understanding the physical aspects of climate change, comprehensive analyses integrating climate, biological, and social sciences are less common. Here we use climate projections under alternative mitigation scenarios to show how changes in environmental variables that limit plant growth could impact ecosystems and people. We show that although the global mean number of days above freezing will increase by up to 7% by 2100 under "business as usual" (representative concentration pathway [RCP] 8.5), suitable growing days will actually decrease globally by up to 11% when other climatic variables that limit plant growth are considered (i.e., temperature, water availability, and solar radiation). Areas in Russia, China, and Canada are projected to gain suitable plant growing days, but the rest of the world will experience losses. Notably, tropical areas could lose up to 200 suitable plant growing days per year. These changes will impact most of the world's terrestrial ecosystems, potentially triggering climate feedbacks. Human populations will also be affected, with up to ~2,100 million of the poorest people in the world (~30% of the world's population) highly vulnerable to changes in the supply of plant-related goods and services. These impacts will be spatially variable, indicating regions where adaptations will be necessary. Changes in suitable plant growing days are projected to be less severe under strong and moderate mitigation scenarios (i.e., RCP 2.6 and RCP 4.5), underscoring the importance of reducing emissions to avoid such disproportionate impacts on ecosystems and people.

Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry.

PubMed

Feng, Xiaodong; Degese, Maria Sol; Iglesias-Bartolome, Ramiro; Vaque, Jose P; Molinolo, Alfredo A; Rodrigues, Murilo; Zaidi, M Raza; Ksander, Bruce R; Merlino, Glenn; Sodhi, Akrit; Chen, Qianming; Gutkind, J Silvio

2014-06-16

Mutually exclusive activating mutations in the GNAQ and GNA11 oncogenes, encoding heterotrimeric Gαq family members, have been identified in ∼ 83% and ∼ 6% of uveal and skin melanomas, respectively. However, the molecular events underlying these GNAQ-driven malignancies are not yet defined, thus limiting the ability to develop cancer-targeted therapies. Here, we focused on the transcriptional coactivator YAP, a critical component of the Hippo signaling pathway that controls organ size. We found that Gαq stimulates YAP through a Trio-Rho/Rac signaling circuitry promoting actin polymerization, independently of phospholipase Cβ and the canonical Hippo pathway. Furthermore, we show that Gαq promotes the YAP-dependent growth of uveal melanoma cells, thereby identifying YAP as a suitable therapeutic target in uveal melanoma, a GNAQ/GNA11-initiated human malignancy. Copyright © 2014 Elsevier Inc. All rights reserved.

Exploring unimolecular dissociation kinetics of ethyl dibromide through electronic structure calculations

NASA Astrophysics Data System (ADS)

Gulvi, Nitin R.; Patel, Priyanka; Badani, Purav M.

2018-04-01

Pathway for dissociation of multihalogenated alkyls is observed to be competitive between molecular and atomic elimination products. Factors such as molecular structure, temperature and pressure are known to influence the same. Hence present work is focussed to explore mechanism and kinetics of atomic (Br) and molecular (HBr and Br2) elimination upon pyrolysis of 1,1- and 1,2-ethyl dibromide (EDB). For this purpose, electronic structure calculations were performed at DFT and CCSD(T) level of theory. In addition to concerted mechanism, an alternate energetically efficient isomerisation pathway has been exploited for molecular elimination. Energy calculations are further complimented by detailed kinetic investigation, over wide range of temperature and pressure, using suitable models like Canonical Transition State Theory, Statistical Adiabatic Channel Model and Troe's formalism. Our calculations suggest high branching ratio for dehydrohalogentation reaction, from both isomers of EDB. Fall off curve depicts good agreement between theoretically estimated and experimentally reported values.

Shape-Dependent Skin Penetration of Silver Nanoparticles: Does It Really Matter?

PubMed Central

Tak, Yu Kyung; Pal, Sukdeb; Naoghare, Pravin K.; Rangasamy, Sabarinathan; Song, Joon Myong

2015-01-01

Advancements in nano-structured materials have facilitated several applications of nanoparticles (NPs). Skin penetration of NPs is a crucial factor for designing suitable topical antibacterial agents with low systemic toxicity. Available reports focus on size-dependent skin penetration of NPs, mainly through follicular pathways. Herein, for the first time, we demonstrate a proof-of-concept study that entails variations in skin permeability and diffusion coefficients, penetration rates and depth-of-penetration of differently shaped silver NPs (AgNPs) via intercellular pathways using both in vitro and in vivo models. The antimicrobial activity of AgNPs is known. Different shapes of AgNPs may exhibit diverse antimicrobial activities and skin penetration capabilities depending upon their active metallic facets. Consideration of the shape dependency of AgNPs in antimicrobial formulations could help developing an ideal topical agent with the highest efficacy and low systemic toxicity. PMID:26584777

Helicases as Prospective Targets for Anti-Cancer Therapy

PubMed Central

Gupta, Rigu; Brosh, Robert M.

2008-01-01

It has been proposed that selective inactivation of a DNA repair pathway may enhance anti-cancer therapies that eliminate cancerous cells through the cytotoxic effects of DNA damaging agents or radiation. Given the unique and critically important roles of DNA helicases in the DNA damage response, DNA repair, and maintenance of genomic stability, a number of strategies currently being explored or in use to combat cancer may be either mediated or enhanced through the modulation of helicase function. The focus of this review will be to examine the roles of helicases in DNA repair that might be suitably targeted by cancer therapeutic approaches. Treatment of cancers with anti-cancer drugs such as small molecule compounds that modulate helicase expression or function is a viable approach to selectively kill cancer cells through the inactivation of helicase-dependent DNA repair pathways, particularly those associated with DNA recombination, replication restart, and cell cycle checkpoint. PMID:18473724

Near-threshold harmonics from a femtosecond enhancement cavity-based EUV source: effects of multiple quantum pathways on spatial profile and yield.

PubMed

Hammond, T J; Mills, Arthur K; Jones, David J

2011-12-05

We investigate the photon flux and far-field spatial profiles for near-threshold harmonics produced with a 66 MHz femtosecond enhancement cavity-based EUV source operating in the tight-focus regime. The effects of multiple quantum pathways in the far-field spatial profile and harmonic yield show a strong dependence on gas jet dynamics, particularly nozzle diameter and position. This simple system, consisting of only a 700 mW Ti:Sapphire oscillator and an enhancement cavity produces harmonics up to 20 eV with an estimated 30-100 μW of power (intracavity) and > 1μW (measured) of power spectrally-resolved and out-coupled from the cavity. While this power is already suitable for applications, a quantum mechanical model of the system indicates substantial improvements should be possible with technical upgrades.

Ab initio genotype–phenotype association reveals intrinsic modularity in genetic networks

PubMed Central

Slonim, Noam; Elemento, Olivier; Tavazoie, Saeed

2006-01-01

Microbial species express an astonishing diversity of phenotypic traits, behaviors, and metabolic capacities. However, our molecular understanding of these phenotypes is based almost entirely on studies in a handful of model organisms that together represent only a small fraction of this phenotypic diversity. Furthermore, many microbial species are not amenable to traditional laboratory analysis because of their exotic lifestyles and/or lack of suitable molecular genetic techniques. As an adjunct to experimental analysis, we have developed a computational information-theoretic framework that produces high-confidence gene–phenotype predictions using cross-species distributions of genes and phenotypes across 202 fully sequenced archaea and eubacteria. In addition to identifying the genetic basis of complex traits, our approach reveals the organization of these genes into generic preferentially co-inherited modules, many of which correspond directly to known enzymatic pathways, molecular complexes, signaling pathways, and molecular machines. PMID:16732191

Molecular and enzymatic characterization of two enzymes BmPCD and BmDHPR involving in the regeneration pathway of tetrahydrobiopterin from the silkworm Bombyx mori.

PubMed

Li, Wentian; Gong, Meixia; Shu, Rui; Li, Xin; Gao, Junshan; Meng, Yan

2015-08-01

Tetrahydrobiopterin (BH4) is an essential cofactor of aromatic amino acid hydroxylases and nitric oxide synthase so that BH4 plays a key role in many biological processes. BH4 deficiency is associated with numerous metabolic syndromes and neuropsychological disorders. BH4 concentration in mammals is maintained through a de novo synthesis pathway and a regeneration pathway. Previous studies showed that the de novo pathway of BH4 is similar between insects and mammals. However, knowledge about the regeneration pathway of BH4 (RPB) is very limited in insects. Several mutants in the silkworm Bombyx mori have been approved to be associated with BH4 deficiency, which are good models to research on the RPB in insects. In this study, homologous genes encoding two enzymes, pterin-4a-carbinolamine dehydratase (PCD) and dihydropteridine reductase (DHPR) involving in RPB have been cloned and identified from B. mori. Enzymatic activity of DHPR was found in the fat body of wild type silkworm larvae. Together with the transcription profiles, it was indicated that BmPcd and BmDhpr might normally act in the RPB of B. mori and the expression of BmDhpr was activated in the brain and sexual glands while BmPcd was expressed in a wider special pattern when the de novo pathway of BH4 was lacked in lemon. Biochemical analyses showed that the recombinant BmDHPR exhibited high enzymatic activity and more suitable parameters to the coenzyme of NADH in vitro. The results in this report give new information about the RPB in B. mori and help in better understanding insect BH4 biosynthetic networks. Copyright © 2015 Elsevier Inc. All rights reserved.

Patterns and variability of projected bioclimatic habitat for Pinus albicaulis in the Greater Yellowstone Area.

PubMed

Chang, Tony; Hansen, Andrew J; Piekielek, Nathan

2014-01-01

Projected climate change at a regional level is expected to shift vegetation habitat distributions over the next century. For the sub-alpine species whitebark pine (Pinus albicaulis), warming temperatures may indirectly result in loss of suitable bioclimatic habitat, reducing its distribution within its historic range. This research focuses on understanding the patterns of spatiotemporal variability for future projected P.albicaulis suitable habitat in the Greater Yellowstone Area (GYA) through a bioclimatic envelope approach. Since intermodel variability from General Circulation Models (GCMs) lead to differing predictions regarding the magnitude and direction of modeled suitable habitat area, nine bias-corrected statistically down-scaled GCMs were utilized to understand the uncertainty associated with modeled projections. P.albicaulis was modeled using a Random Forests algorithm for the 1980-2010 climate period and showed strong presence/absence separations by summer maximum temperatures and springtime snowpack. Patterns of projected habitat change by the end of the century suggested a constant decrease in suitable climate area from the 2010 baseline for both Representative Concentration Pathways (RCPs) 8.5 and 4.5 climate forcing scenarios. Percent suitable climate area estimates ranged from 2-29% and 0.04-10% by 2099 for RCP 8.5 and 4.5 respectively. Habitat projections between GCMs displayed a decrease of variability over the 2010-2099 time period related to consistent warming above the 1910-2010 temperature normal after 2070 for all GCMs. A decreasing pattern of projected P.albicaulis suitable habitat area change was consistent across GCMs, despite strong differences in magnitude. Future ecological research in species distribution modeling should consider a full suite of GCM projections in the analysis to reduce extreme range contractions/expansions predictions. The results suggest that restoration strageties such as planting of seedlings and controlling competing vegetation may be necessary to maintain P.albicaulis in the GYA under the more extreme future climate scenarios.

Patterns and Variability of Projected Bioclimatic Habitat for Pinus albicaulis in the Greater Yellowstone Area

PubMed Central

Chang, Tony; Hansen, Andrew J.; Piekielek, Nathan

2014-01-01

Projected climate change at a regional level is expected to shift vegetation habitat distributions over the next century. For the sub-alpine species whitebark pine (Pinus albicaulis), warming temperatures may indirectly result in loss of suitable bioclimatic habitat, reducing its distribution within its historic range. This research focuses on understanding the patterns of spatiotemporal variability for future projected P.albicaulis suitable habitat in the Greater Yellowstone Area (GYA) through a bioclimatic envelope approach. Since intermodel variability from General Circulation Models (GCMs) lead to differing predictions regarding the magnitude and direction of modeled suitable habitat area, nine bias-corrected statistically down-scaled GCMs were utilized to understand the uncertainty associated with modeled projections. P.albicaulis was modeled using a Random Forests algorithm for the 1980–2010 climate period and showed strong presence/absence separations by summer maximum temperatures and springtime snowpack. Patterns of projected habitat change by the end of the century suggested a constant decrease in suitable climate area from the 2010 baseline for both Representative Concentration Pathways (RCPs) 8.5 and 4.5 climate forcing scenarios. Percent suitable climate area estimates ranged from 2–29% and 0.04–10% by 2099 for RCP 8.5 and 4.5 respectively. Habitat projections between GCMs displayed a decrease of variability over the 2010–2099 time period related to consistent warming above the 1910–2010 temperature normal after 2070 for all GCMs. A decreasing pattern of projected P.albicaulis suitable habitat area change was consistent across GCMs, despite strong differences in magnitude. Future ecological research in species distribution modeling should consider a full suite of GCM projections in the analysis to reduce extreme range contractions/expansions predictions. The results suggest that restoration strageties such as planting of seedlings and controlling competing vegetation may be necessary to maintain P.albicaulis in the GYA under the more extreme future climate scenarios. PMID:25372719

Shifts in the suitable habitat available for brown trout (Salmo trutta L.) under short-term climate change scenarios.

PubMed

Muñoz-Mas, R; Lopez-Nicolas, A; Martínez-Capel, F; Pulido-Velazquez, M

2016-02-15

The impact of climate change on the habitat suitability for large brown trout (Salmo trutta L.) was studied in a segment of the Cabriel River (Iberian Peninsula). The future flow and water temperature patterns were simulated at a daily time step with M5 models' trees (NSE of 0.78 and 0.97 respectively) for two short-term scenarios (2011-2040) under the representative concentration pathways (RCP 4.5 and 8.5). An ensemble of five strongly regularized machine learning techniques (generalized additive models, multilayer perceptron ensembles, random forests, support vector machines and fuzzy rule base systems) was used to model the microhabitat suitability (depth, velocity and substrate) during summertime and to evaluate several flows simulated with River2D©. The simulated flow rate and water temperature were combined with the microhabitat assessment to infer bivariate habitat duration curves (BHDCs) under historical conditions and climate change scenarios using either the weighted usable area (WUA) or the Boolean-based suitable area (SA). The forecasts for both scenarios jointly predicted a significant reduction in the flow rate and an increase in water temperature (mean rate of change of ca. -25% and +4% respectively). The five techniques converged on the modelled suitability and habitat preferences; large brown trout selected relatively high flow velocity, large depth and coarse substrate. However, the model developed with support vector machines presented a significantly trimmed output range (max.: 0.38), and thus its predictions were banned from the WUA-based analyses. The BHDCs based on the WUA and the SA broadly matched, indicating an increase in the number of days with less suitable habitat available (WUA and SA) and/or with higher water temperature (trout will endure impoverished environmental conditions ca. 82% of the days). Finally, our results suggested the potential extirpation of the species from the study site during short time spans. Copyright © 2015 Elsevier B.V. All rights reserved.

Unitary IPSPs evoked by interneurons at the stratum radiatum-stratum lacunosum-moleculare border in the CA1 area of the rat hippocampus in vitro

PubMed Central

Vida, Imre; Halasy, Katalin; Szinyei, Csaba; Somogyi, Peter; Buhl, Eberhard H

1998-01-01

Hippocampal non-principal neurons at the stratum radiatum-stratum lacunosum-moleculare border (R-LM interneurons) of the CA1 area may constitute several cell classes and have been implicated in the generation of GABAergic unitary IPSPs. Using biocytin-filled electrodes we recorded R-LM interneurons intracellularly in vitro and determined their postsynaptic effects in concomitantly recorded pyramidal cells. Light microscopic analysis revealed four populations of R-LM interneurons with distinct axons: (1) basket cells (n= 4) with axons predominantly ramifying in the pyramidal cell layer; (2) Schaffer collateral/commissural pathway-associated interneurons (n= 10) stratifying in stratum radiatum and, to a lesser extent, stratum oriens; (3) perforant pathway-associated interneurons (n= 6) innervating the perforant path termination zone in stratum lacunosum-moleculare of the CA1 area as well as equivalent portions of the dentate gyrus and subiculum; and (4) neurogliaform interneurons (n= 2) characterized by their dense, compact axonal and dendritic arbour. Random electron microscopic sampling of synaptic targets revealed a preponderance of pyramidal neurons as postsynaptic elements. Basket cells had a synaptic target preference for somata and proximal dendrites, whereas the remainder of R-LM interneurons innervated dendritic shafts and spines. The axon of dendrite-targeting cells formed up to six putative contacts with individual postsynaptic pyramidal cells. Anatomically recovered R-LM interneurons (n= 22) had a mean resting membrane potential of -56.7 ± 3.6 mV, a membrane time constant of 12.9 ± 7.7 ms and an input resistance of 86.4 ± 29.2 MΩ. Depolarizing current pulses generally elicited overshooting action potentials (70.8 ± 6.9 mV) which had a mean duration, when measured at half-amplitude, of 0.7 ± 0.1 ms. In response to prolonged (> 200 ms) depolarizing current pulses all R-LM interneurons displayed (a varying degree of) spike frequency adaptation. Basket cells, Schaffer-associated and neurogliaform interneurons elicited small-amplitude (< 2 mV), short-latency IPSPs in postsynaptic pyramids (n= 5, 13 and 1, respectively). Those interactions in which an effect was elicited with the repetitive activation of the presynaptic neuron (n= 13) showed a substantial degree of postsynaptic response summation. Unitary IPSPs had fast kinetics and, whenever tested (n= 5; 1 basket cell and 4 Schaffer-associated interneurons), were abolished by the GABAA receptor antagonist bicuculline. Thus, R-LM interneurons comprise several distinct populations which evoke fast GABAA receptor-mediated IPSPs. The domain-specific innervation of postsynaptic pyramidal cells suggests functionally diverse effects on the integration of afferent information in functionally non-equivalent compartments of pyramidal cells. PMID:9503336

Present and Future of Dengue Fever in Nepal: Mapping Climatic Suitability by Ecological Niche Model

PubMed Central

Cao, Chunxiang; Xu, Min; Pandit, Shreejana

2018-01-01

Both the number of cases of dengue fever and the areas of outbreaks within Nepal have increased significantly in recent years. Further expansion and range shift is expected in the future due to global climate change and other associated factors. However, due to limited spatially-explicit research in Nepal, there is poor understanding about the present spatial distribution patterns of dengue risk areas and the potential range shift due to future climate change. In this context, it is crucial to assess and map dengue fever risk areas in Nepal. Here, we used reported dengue cases and a set of bioclimatic variables on the MaxEnt ecological niche modeling approach to model the climatic niche and map present and future (2050s and 2070s) climatically suitable areas under different representative concentration pathways (RCP2.6, RCP6.0 and RCP8.5). Simulation-based estimates suggest that climatically suitable areas for dengue fever are presently distributed throughout the lowland Tarai from east to west and in river valleys at lower elevations. Under the different climate change scenarios, these areas will be slightly shifted towards higher elevation with varied magnitude and spatial patterns. Population exposed to climatically suitable areas of dengue fever in Nepal is anticipated to further increase in both 2050s and 2070s on all the assumed emission scenarios. These findings could be instrumental to plan and execute the strategic interventions for controlling dengue fever in Nepal. PMID:29360797

Zebrafish CiA interneurons are late-born primary neurons.

PubMed

Yeo, Sang-Yeob

2009-12-11

Pax2 is a neural-related transcription factor downstream of Notch signaling and is expressed in the developing spinal cord of zebrafish, including in CiA interneurons. However, the characteristics of pax2-positive neurons are largely unknown. The goal of this study was to characterize Pax2-positive neurons by examining their expression in embryos in which Notch function had been knocked down by mutation or injection of a morpholino or mRNA. I found that Pax2-positive CiA interneurons were late-differentiating primary neurons. pax2.1 was expressed in CoPA commissural neurons and CiA interneurons at 26 hpf. The number of pax2.1-positive cells increased in mind bomb mutant embryos or embryos injected with Su(H)1-MO, but not in cells injected with Xenopus Delta or Delta(stu) mRNA. These observations imply that Notch signaling plays a role in regulating the number of CiA neurons by preventing uncommitted precursors from acquiring a neuronal fate during vertebrate development.

The characterization of a zebrafish mid-hindbrain mutant, mid-hindbrain gone (mgo).

PubMed

Shima, Takaki; Znosko, Wade; Tsang, Michael

2009-04-01

The vertebrate mid-hindbrain boundary (MHB) is a crucial morphological structure required for patterning and neural differentiation of the midbrain and anterior hindbrain. We isolated a novel zebrafish mutant, MHB gone (mgo), that exhibited a defective MHB. Expression of engrailed3 in the prospective MHB was absent at the 1-somite stage, suggesting that initiation of the isthmic organizer was disrupted in mgo mutants. Complementation test with mgo and noi, in which the pax2a gene is mutated, infer that the mgo mutant may represent a novel noi allele. However, pronephric, otic vesicle, and commissural axonal defects described in noi mutants were not associated with mgo mutants. Genetic mapping revealed that the mgo mutation is linked to the Pax2a locus, but no mutation was detected in pax2a exons or within intron-exon boundaries. Based on these findings, we propose that the mgo mutation genetically interacts with pax2a required for the initiation of MHB formation. Copyright 2009 Wiley-Liss, Inc.

Dynamics of myelin content decrease in the rat stroke model

NASA Astrophysics Data System (ADS)

Kisel, A.; Khodanovich, M.; Atochin, D.; Mustafina, L.; Yarnykh, V.

2017-08-01

The majority of studies were usually focused on neuronal death after brain ischemia; however, stroke affects all cell types including oligodendrocytes that form myelin sheath in the CNS. Our study is focused on the changes of myelin content in the ischemic core and neighbor structures in early terms (1, 3 and 10 days) after stroke. Stroke was modeled with middle cerebral artery occlusion (MCAo) in 15 male rats that were divided into three groups by time points after operation. Brain sections were histologically stained with Luxol Fast Blue (LFB) for myelin quantification. The significant demyelination was found in the ischemic core, corpus callosum, anterior commissure, whereas myelin content was increased in caudoputamen, internal capsule and piriform cortex compared with the contralateral hemisphere. The motor cortex showed a significant increase of myelin content on the 1st day and a significant decrease on the 3rd and 10th days after MCAo. These results suggest that stroke influences myelination not only in the ischemic core but also in distant structures.

Proposal of landmarks for clamping neurovascular elements during endoscopic surgery of the supraglottic region.

PubMed

Souvirón, R; Maranillo, E; Vázquez, T; Patel, N; McHanwell, S; Cobeta, I; Scola, B; Sañudo, J

2013-01-01

Bleeding within the supraglottic region can be a lethal complication after CO(2) laser microsurgery. Our aim was to propose endoluminal anatomical landmarks to locate the superior laryngeal vessels resulting in a safer microsurgery. Endoluminal dissections were made in 22 larynges without laryngeal disease. The neurovascular structures were in the superior third of a triangle defined by the vocal process, the anterior commissure, and the epiglottic attachment of the aryepiglottic fold. They overlapped in 4 different ways: pattern I (70.4%): superior laryngeal vein (SLV), superior laryngeal artery (SLA), and internal laryngeal nerve (ILN); pattern II (13.6%): SLA, SLV, ILN; pattern III (4.6%): SLV, ILN, and SLA; pattern IV (4.6%): SLA, ILN, and SLV. Microsurgery in the supraglottic region may be safer if surgeons are aware of the superior third of the above-defined triangle, "danger area", where the vascular elements of this region are located. Copyright © 2012 Wiley Periodicals, Inc.

Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance

PubMed Central

Tischfield, Max A.; Baris, Hagit N.; Wu, Chen; Rudolph, Guenther; Van Maldergem, Lionel; He, Wei; Chan, Wai-Man; Andrews, Caroline; Demer, Joseph L.; Robertson, Richard L.; Mackey, David A.; Ruddle, Jonathan B.; Bird, Thomas D.; Gottlob, Irene; Pieh, Christina; Traboulsi, Elias I.; Pomeroy, Scott L.; Hunter, David G.; Soul, Janet S.; Newlin, Anna; Sabol, Louise J.; Doherty, Edward J.; de Uzcátegui, Clara E.; de Uzcátegui, Nicolas; Collins, Mary Louise Z.; Sener, Emin C.; Wabbels, Bettina; Hellebrand, Heide; Meitinger, Thomas; de Berardinis, Teresa; Magli, Adriano; Schiavi, Costantino; Pastore-Trossello, Marco; Koc, Feray; Wong, Agnes M.; Levin, Alex V.; Geraghty, Michael T.; Descartes, Maria; Flaherty, Maree; Jamieson, Robyn V.; Møller, H. U.; Meuthen, Ingo; Callen, David F.; Kerwin, Janet; Lindsay, Susan; Meindl, Alfons; Gupta, Mohan L.; Pellman, David; Engle, Elizabeth C.

2011-01-01

We report that eight heterozygous missense mutations in TUBB3, encoding the neuron-specific β-tubulin isotype III, result in a spectrum of human nervous system disorders we now call the TUBB3 syndromes. Each mutation causes the ocular motility disorder CFEOM3, whereas some also result in intellectual and behavioral impairments, facial paralysis, and/or later-onset axonal sensorimotor polyneuropathy. Neuroimaging reveals a spectrum of abnormalities including hypoplasia of oculomotor nerves, and dysgenesis of the corpus callosum, anterior commissure, and corticospinal tracts. A knock-in disease mouse model reveals axon guidance defects without evidence of cortical cell migration abnormalities. We show the disease-associated mutations can impair tubulin heterodimer formation in vitro, although folded mutant heterodimers can still polymerize into microtubules. Modeling each mutation in yeast tubulin demonstrates that all alter dynamic instability whereas a subset disrupts the interaction of microtubules with kinesin motors. These findings demonstrate normal TUBB3 is required for axon guidance and maintenance in mammals. PMID:20074521

An N-methyl-D-aspartate receptor-independent excitatory action of partial reduction of extracellular [Mg2+] in CA1-region of rat hippocampal slices.

PubMed

Hamon, B; Stanton, P K; Heinemann, U

1987-03-31

Partial reduction of [Mg2+]o from 2 to 1 mM markedly enhanced neuronal responses evoked by Schaffer collateral-commissural fiber stimulation in the CA1-region of rat hippocampal slices. The amplitude of extracellular population potentials recorded in the CA1-pyramidal cell layer and maximum dV/dt of extracellular population EPSP's recorded in the CA1-pyramidal apical dendritic layer were both increased. However, unlike findings from slices where Mg2+ was completely removed from the bathing medium, there was no spontaneous or evoked epileptiform activity, and the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (2-APV) did not antagonize the enhancement of evoked responses. These results indicate that, in addition to the participation of NMDA receptors in the epileptiform activity observed when Mg2+ is completely removed from the bathing medium, there is also an NMDA receptor-independent excitatory action of partial reduction of [Mg2+]o in hippocampal slices.

14 year follow-up for a severe electrical burn to mouth and lip: case report.

PubMed

Valencia, Roberto; Garcia, Javier; Espinosa, Roberto; Saadia, Marc; Valencia, Evaristo

2010-01-01

Electrical burns range from 4 to 7% of the total burn accidents and many of them affect primarily children biting on a live wire. Great confusion exists in the literature about the proper management of electrical burns to the mouth in the acute and late phases. 14 year results are shown in a severe electrical burn sustained in a 1 year 2 months old girl, involving 90% of the lips and commissures, tongue, alveolar ridges and teeth (primary central incisors and permanent dental germs). Two weeks after she was out of danger, an active splint expansion device was built and used for 8 months to prevent secondary microstomia. Later a new active splint device was used for a year after lip plastic surgery. At age 13, orthopedics and orthodontics were accomplished with a lip tattoo completed at age 15. No matter how good the final esthetic and occlusal results are, prevention is always the best option.

Echocardiographic Assessment of Mantle Radiation Mitral Stenosis.

PubMed

Bastiaenen, Rachel; Sneddon, James; Sharma, Rajan

2016-02-01

The long-term sequelae of mantle radiotherapy include lung disease and cardiac disorders. Dyspnea on exertion is a common complaint and can be due to one or more pathologies. We describe a case of mantle radiotherapy-induced mitral stenosis, characterized by aorto-mitral continuity calcification and absent commissural fusion which precludes balloon valvotomy. The latency period is long, and this patient presented 42 years after radiotherapy. Importantly, as previously described with radiation-induced valve disease, significant mitral stenosis developed 10 years after surgery for significant aortic stenosis. Two-dimensional and three-dimensional transthoracic and transesophageal echocardiography should be considered during assessment of symptomatic survivors of Hodgkin's disease where the index of suspicion for valvular stenosis increases over time. Given the natural history of mantle radiation valvular disease, a lower threshold for surgical intervention in radiation-induced mitral stenosis may need to be considered if cardiac surgery is planned for other reasons in order to avoid repeated sternotomy in patients with prior irradiation. © 2015, Wiley Periodicals, Inc.

A case of the corpus callosum and alien hand syndrome from a discrete paracallosal lesion.

PubMed

Faber, Raymond; Azad, Alvi; Reinsvold, Richard

2010-08-01

Here we present a patient with an isolated paracallosal brain lesion who exhibited behavioral changes associated with the corpus callosum syndrome (CCS) including features of the alien hand syndrome (AHS). The CCS is also known as the split-brain syndrome, the syndrome of hemisphere disconnection, the syndrome of brain bisection and the syndrome of the cerebral commissures. Because most reported cases of CCS were caused by tumors which extended beyond the corpus callosum (CC) and did not always induce a complete disconnection, there was much controversy about the role of the CC and the existence of a specific CCS. Aside from surgically based cases, the full complement of the CCS is infrequently clinically encountered. The patient described has a classic CCS from natural causes. This case report is unique in exhibiting a complete CCS with AHS secondary to an ischemic event affecting the left pericallosal region. To our knowledge this is the first case report of such a combination.

Craniofacial anthropometry in newborns of Sikkimese origin.

PubMed

Sinha, P; Tamang, B K; Chakraborty, S

2014-06-01

Head and face dimensions vary according to race and geographical zone. Hereditary factors also greatly affect the size and shape of the head. There are important medical applications of craniofacial data specific to different racial and ethnic groups. Various cranial and facial anthropometric parameters were assessed in singleton, healthy, full-term newborns of Sikkimese origin in a tertiary care hospital in Sikkim, India. The data were then analysed to determine statistically significant differences between sexes. Forty-five newborns were included in the study. Both male and female newborns were observed to be hyperbrachycephalic and hyperleptoprosopic. The only significant difference between the sexes was in commissural length, which was observed to be greater in male newborns. Craniofacial parameters in Sikkimese newborns vary in comparison with those of other newborns from around the world. Larger studies are needed in order to reveal sex-related variations. Similar studies on various racial groups in North-East India are needed to establish standards for populations with East Asian features.

Computer ranking of the sequence of appearance of 73 features of the brain and related structures in staged human embryos during the sixth week of development.

PubMed

O'Rahilly, R; Müller, F; Hutchins, G M; Moore, G W

1987-09-01

The sequence of events in the development of the brain in human embryos, already published for stages 8-15, is here continued for stages 16 and 17. With the aid of a computerized bubble-sort algorithm, 71 individual embryos were ranked in ascending order of the features present. Whereas these numbered 100 in the previous study, the increasing structural complexity gave 27 new features in the two stages now under investigation. The chief characteristics of stage 16 (approximately 37 postovulatory days) are protruding basal nuclei, the caudal olfactory elevation (olfactory tubercle), the tectobulbar tracts, and ascending fibers to the cerebellum. The main features of stage 17 (approximately 41 postovulatory days) are the cortical nucleus of the amygdaloid body, an intermediate layer in the tectum mesencephali, the posterior commissure, and the habenulo-interpeduncular tract. In addition, a typical feature at stage 17 is the crescentic shape of the lens cavity.

A cascade of morphogenic signaling initiated by the meninges controls corpus callosum formation.

PubMed

Choe, Youngshik; Siegenthaler, Julie A; Pleasure, Samuel J

2012-02-23

The corpus callosum is the most prominent commissural connection between the cortical hemispheres, and numerous neurodevelopmental disorders are associated with callosal agenesis. By using mice either with meningeal overgrowth or selective loss of meninges, we have identified a cascade of morphogenic signals initiated by the meninges that regulates corpus callosum development. The meninges produce BMP7, an inhibitor of callosal axon outgrowth. This activity is overcome by the induction of expression of Wnt3 by the callosal pathfinding neurons, which antagonize the inhibitory effects of BMP7. Wnt3 expression in the cingulate callosal pathfinding axons is developmentally regulated by another BMP family member, GDF5, which is produced by the adjacent Cajal-Retzius neurons and turns on before outgrowth of the callosal axons. The effects of GDF5 are in turn under the control of a soluble GDF5 inhibitor, Dan, made by the meninges. Thus, the meninges and medial neocortex use a cascade of signals to regulate corpus callosum development. Copyright © 2012 Elsevier Inc. All rights reserved.

A cascade of morphogenic signaling initiated by the meninges controls corpus callosum formation

PubMed Central

Choe, Youngshik; Siegenthaler, Julie A.; Pleasure, Samuel J.

2012-01-01

Summary The corpus callosum is the most prominent commissural connection between the cortical hemispheres, and numerous neurodevelopmental disorders are associated with callosal agenesis. Using mice with either meningeal overgrowth or selective loss of meninges, we’ve identified a cascade of morphogenic signals initiated by the meninges that regulates corpus callosum development. The meninges produce BMP7, an inhibitor of callosal axon outgrowth. This activity is overcome by the induction of expression of Wnt3 by the callosal pathfinding neurons, which antagonizes the inhibitory effects of BMP7. Wnt3 expression in the cingulate callosal pathfinding axons is developmentally regulated by another BMP family member, GDF5, produced by the adjacent Cajal-Retzius neurons and turns on before outgrowth of the callosal axons. The effects of GDF5 are in turn under the control of a soluble GDF5 inhibitor, Dan, made by the meninges. Thus, the meninges and medial neocortex use a cascade of signals to regulate corpus callosum development. PMID:22365545

Altered respiratory response to substance P and reduced NK1 receptor binding in the nucleus of the solitary tract of aged rats.

PubMed

Mazzone, S B; Geraghty, D P

1999-04-24

The respiratory response to microinjection of substance P (SP) into the commissural nucleus of the solitary tract (cNTS) and binding of [125I]-Bolton-Hunter SP ([125I]-BHSP) to brain stem NK1 receptors were compared in young and aged rats. Injection of SP (750 pmol) into the cNTS of young rats (2 months) increased tidal volume (VT) but had no effect on respiratory rate (f). In aged rats (19-21 months), injection of SP had no significant effect on f or VT. The NTS of aged rats displayed significantly lower specific [125I]-BHSP binding than young rats, indicating a reduction in the number in NK1 receptors. These findings show that the respiratory response to microinjection of SP into the cNTS of aged rats is severely blunted and that this phenomenon may be due to a decrease in the number of NK1 receptors in the NTS. Copyright 1999 Elsevier Science B.V.

Design and analysis of metabolic pathways supporting formatotrophic growth for electricity-dependent cultivation of microbes.

PubMed

Bar-Even, Arren; Noor, Elad; Flamholz, Avi; Milo, Ron

2013-01-01

Electrosynthesis is a promising approach that enables the biological production of commodities, like fuels and fine chemicals, using renewably produced electricity. Several techniques have been proposed to mediate the transfer of electrons from the cathode to living cells. Of these, the electroproduction of formate as a mediator seems especially promising: formate is readily soluble, of low toxicity and can be produced at relatively high efficiency and at reasonable current density. While organisms that are capable of formatotrophic growth, i.e. growth on formate, exist naturally, they are generally less suitable for bulk cultivation and industrial needs. Hence, it may be helpful to engineer a model organism of industrial relevance, such as E. coli, for growth on formate. There are numerous metabolic pathways that can potentially support formatotrophic growth. Here we analyze these diverse pathways according to various criteria including biomass yield, thermodynamic favorability, chemical motive force, kinetics and the practical challenges posed by their expression. We find that the reductive glycine pathway, composed of the tetrahydrofolate system, the glycine cleavage system, serine hydroxymethyltransferase and serine deaminase, is a promising candidate to support electrosynthesis in E. coli. The approach presented here exemplifies how combining different computational approaches into a systematic analysis methodology provides assistance in redesigning metabolism. This article is part of a Special Issue entitled: Metals in Bioenergetics and Biomimetics Systems. Copyright © 2012 Elsevier B.V. All rights reserved.

A single-run liquid chromatography mass spectrometry method to quantify neuroactive kynurenine pathway metabolites in rat plasma.

PubMed

Orsatti, Laura; Speziale, Roberto; Orsale, Maria Vittoria; Caretti, Fulvia; Veneziano, Maria; Zini, Matteo; Monteagudo, Edith; Lyons, Kathryn; Beconi, Maria; Chan, Kelvin; Herbst, Todd; Toledo-Sherman, Leticia; Munoz-Sanjuan, Ignacio; Bonelli, Fabio; Dominguez, Celia

2015-03-25

Neuroactive metabolites in the kynurenine pathway of tryptophan catabolism are associated with neurodegenerative disorders. Tryptophan is transported across the blood-brain barrier and converted via the kynurenine pathway to N-formyl-L-kynurenine, which is further degraded to L-kynurenine. This metabolite can then generate a group of metabolites called kynurenines, most of which have neuroactive properties. The association of tryptophan catabolic pathway alterations with various central nervous system (CNS) pathologies has raised interest in analytical methods to accurately quantify kynurenines in body fluids. We here describe a rapid and sensitive reverse-phase HPLC-MS/MS method to quantify L-kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxy-L-kynurenine (3HK) and anthranilic acid (AA) in rat plasma. Our goal was to quantify these metabolites in a single run; given their different physico-chemical properties, major efforts were devoted to develop a chromatography suitable for all metabolites that involves plasma protein precipitation with acetonitrile followed by chromatographic separation by C18 RP chromatography, detected by electrospray mass spectrometry. Quantitation range was 0.098-100 ng/ml for 3HK, 9.8-20,000 ng/ml for KYN, 0.49-1000 ng/ml for KYNA and AA. The method was linear (r>0.9963) and validation parameters were within acceptance range (calibration standards and QC accuracy within ±30%). Copyright © 2015 Elsevier B.V. All rights reserved.

Learning visuomotor transformations for gaze-control and grasping.

PubMed

Hoffmann, Heiko; Schenck, Wolfram; Möller, Ralf

2005-08-01

For reaching to and grasping of an object, visual information about the object must be transformed into motor or postural commands for the arm and hand. In this paper, we present a robot model for visually guided reaching and grasping. The model mimics two alternative processing pathways for grasping, which are also likely to coexist in the human brain. The first pathway directly uses the retinal activation to encode the target position. In the second pathway, a saccade controller makes the eyes (cameras) focus on the target, and the gaze direction is used instead as positional input. For both pathways, an arm controller transforms information on the target's position and orientation into an arm posture suitable for grasping. For the training of the saccade controller, we suggest a novel staged learning method which does not require a teacher that provides the necessary motor commands. The arm controller uses unsupervised learning: it is based on a density model of the sensor and the motor data. Using this density, a mapping is achieved by completing a partially given sensorimotor pattern. The controller can cope with the ambiguity in having a set of redundant arm postures for a given target. The combined model of saccade and arm controller was able to fixate and grasp an elongated object with arbitrary orientation and at arbitrary position on a table in 94% of trials.

Harnessing the complexity of gene expression data from cancer: from single gene to structural pathway methods

PubMed Central

2012-01-01

High-dimensional gene expression data provide a rich source of information because they capture the expression level of genes in dynamic states that reflect the biological functioning of a cell. For this reason, such data are suitable to reveal systems related properties inside a cell, e.g., in order to elucidate molecular mechanisms of complex diseases like breast or prostate cancer. However, this is not only strongly dependent on the sample size and the correlation structure of a data set, but also on the statistical hypotheses tested. Many different approaches have been developed over the years to analyze gene expression data to (I) identify changes in single genes, (II) identify changes in gene sets or pathways, and (III) identify changes in the correlation structure in pathways. In this paper, we review statistical methods for all three types of approaches, including subtypes, in the context of cancer data and provide links to software implementations and tools and address also the general problem of multiple hypotheses testing. Further, we provide recommendations for the selection of such analysis methods. Reviewers This article was reviewed by Arcady Mushegian, Byung-Soo Kim and Joel Bader. PMID:23227854

Improved self-confidence was a mechanism of action in two geriatric trials evaluating physical interventions.

PubMed

Peduzzi, Peter; Guo, Zhenchao; Marottoli, Richard A; Gill, Thomas M; Araujo, Katy; Allore, Heather G

2007-01-01

To evaluate the mechanisms of action in two successful geriatric clinical trials that tested multicomponent physical conditioning programs and to determine whether the pathways for overall benefit were through improvement in physical ability and/or self-confidence. PREHAB and DRIVER were conducted by the Yale Pepper Center. PREHAB participants received an individualized program that focused on the impairments present (standardly tailored design); DRIVER participants received the entire intervention (global design). PREHAB enrolled 188 community-living persons, aged 75 years or older, who were physically frail but ambulatory; DRIVER enrolled 178 drivers aged 70 years or older with physical impairments associated with poor driving performance. The primary outcome for PREHAB was a disability score and for DRIVER it was a driving score; potential mediators were measures of physical ability and self-confidence. In PREHAB, pathways for the intervention were established through improvement in physical ability and self-confidence. In DRIVER, there was some evidence for a pathway through improved driving self-confidence but not through physical ability; however, the intervention effect was largely unexplained. Multicomponent physical interventions may operate through psychological mechanisms, and these mechanisms should be anticipated in trial designs so that the component effects can be suitably evaluated.

Apigenin exhibits protective effects in a mouse model of d-galactose-induced aging via activating the Nrf2 pathway.

PubMed

Sang, Ying; Zhang, Fan; Wang, Heng; Yao, Jianqiao; Chen, Ruichuan; Zhou, Zhengdao; Yang, Kun; Xie, Yan; Wan, Tianfeng; Ding, Hong

2017-06-21

The aim of the present research was to study the protective effects and underlying mechanisms of apigenin on d-galactose-induced aging mice. Firstly, apigenin exhibited a potent antioxidant activity in vitro. Secondly, d-galactose was administered by subcutaneous injection once daily for 8 weeks to establish an aging mouse model to investigate the protective effect of apigenin. We found that apigenin supplementation significantly ameliorated aging-related changes such as behavioral impairment, decreased organic index, histopathological injury, increased senescence-associated β-galactosidase (SAβ-gal) activity and advanced glycation end product (AGE) level. Further data showed that apigenin facilitated Nrf2 nuclear translocation both in aging mice and normal young mice, and the Nrf2 expression of normal young mice was higher than that of natural senile mice. In addition, the expressions of Nrf2 downstream gene targets, including HO-1 and NQO1, were also promoted by apigenin administration. Moreover, apigenin also decreased the MDA level and elevated SOD and CAT activities. In conclusion, focusing on the Nrf2 pathway is a suitable strategy to delay the aging process, and apigenin may exert an anti-senescent effect process via activating the Nrf2 pathway.

Is the secret for a successful aging to keep track of cancer pathways?

PubMed

Tramontano, Donatella; De Amicis, Francesca

2018-06-15

A successful aging could be gained by life satisfaction, social functioning, or psychological resources and, definitely, by increasing resistance to diverse age-related pathologies. Nowadays, cancer can be considered an age-related disease since the incidence of most cancers increases with age, rising more rapidly beginning in midlife. Although adults with extended longevity are less likely to develop cancer, it is now emerging that aging and cancer share common molecular links, and thus targeting these mechanisms may be suitable to treat multiple disorders, for the prolonging of healthy aging. At present, one of the cornerstones of antiaging is hormone-replacement therapy to treat diseases associated with a state of age-related sex-hormone deficiency in women and men; however, many studies question the relationship of hormone replacement to cancer recurrence. Here, we discuss signaling and metabolic molecular crossroad linking aging and cancer. This is useful to argue about the current knowledge of prolongevity and druggable targets and to motivate specific intervention strategies that could modify practices of the aging population, activating multiple longevity pathways but keeping track of cancer pathways, thereby potentially preserving health status. © 2018 Wiley Periodicals, Inc.

Inhibitors of Ras-SOS Interactions.

PubMed

Lu, Shaoyong; Jang, Hyunbum; Zhang, Jian; Nussinov, Ruth

2016-04-19

Activating Ras mutations are found in about 30 % of human cancers. Ras activation is regulated by guanine nucleotide exchange factors, such as the son of sevenless (SOS), which form protein-protein interactions (PPIs) with Ras and catalyze the exchange of GDP by GTP. This is the rate-limiting step in Ras activation. However, Ras surfaces lack any evident suitable pockets where a molecule might bind tightly, rendering Ras proteins still 'undruggable' for over 30 years. Among the alternative approaches is the design of inhibitors that target the Ras-SOS PPI interface, a strategy that is gaining increasing recognition for treating Ras mutant cancers. Herein we focus on data that has accumulated over the past few years pertaining to the design of small-molecule modulators or peptide mimetics aimed at the interface of the Ras-SOS PPI. We emphasize, however, that even if such Ras-SOS therapeutics are potent, drug resistance may emerge. To counteract this development, we propose "pathway drug cocktails", that is, drug combinations aimed at parallel (or compensatory) pathways. A repertoire of classified cancer, cell/tissue, and pathway/protein combinations would be beneficial toward this goal. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Preparation of holo- and malonyl-[acyl-carrier-protein] in a manner suitable for analog development.

PubMed

Marcella, Aaron M; Jing, Fuyuan; Barb, Adam W

2015-11-01

The fatty acid biosynthetic pathway generates highly reduced carbon based molecules. For this reason fatty acid synthesis is a target of pathway engineering to produce novel specialty or commodity chemicals using renewable techniques to supplant molecules currently derived from petroleum. Malonyl-[acyl carrier protein] (malonyl-ACP) is a key metabolite in the fatty acid pathway and donates two carbon units to the growing fatty acid chain during each step of biosynthesis. Attempts to test engineered fatty acid biosynthesis enzymes in vitro will require malonyl-ACP or malonyl-ACP analogs. Malonyl-ACP is challenging to prepare due to the instability of the carboxylate leaving group and the multiple steps of post-translational modification required to activate ACP. Here we report the expression and purification of holo- and malonyl-ACP from Escherichia coli with high yields (>15 mg per L of expression). The malonyl-ACP is efficiently recognized by the E. coli keto-acyl synthase enzyme, FabH. A FabH assay using malonyl-ACP and a coumarin-based fluorescent reagent is described that provides a high throughput alternative to reported radioactive assays. Copyright © 2015 Elsevier Inc. All rights reserved.

Porous liquids: A promising class of media for gas separation

DOE PAGES

Zhang, Jinshui; Chai, Song -Hai; Qiao, Zhen -An; ...

2014-11-17

In porous liquids with empty cavities we successfully has been successfully fabricated by surface engineering of hollow structures with suitable corona and canopy species. By taking advantage of the liquid-like polymeric matrices as a separation medium and the empty cavities as gas transport pathway, this unique porous liquid can function as a promising candidate for gas separation. A facile synthetic strategy can be further extended to other types of nanostructure-based porous liquid fabrication, opening up new opportunities for preparation of porous liquids with attractive properties for specific tasks.

Module Degradation Mechanisms Studied by a Multi-Scale Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnston, Steve; Al-Jassim, Mowafak; Hacke, Peter

2016-11-21

A key pathway to meeting the Department of Energy SunShot 2020 goals is to reduce financing costs by improving investor confidence through improved photovoltaic (PV) module reliability. A comprehensive approach to further understand and improve PV reliability includes characterization techniques and modeling from module to atomic scale. Imaging techniques, which include photoluminescence, electroluminescence, and lock-in thermography, are used to locate localized defects responsible for module degradation. Small area samples containing such defects are prepared using coring techniques and are then suitable and available for microscopic study and specific defect modeling and analysis.

Activation of sorbitol pathway in metabolic syndrome and increased susceptibility to cataract in Wistar-Obese rats

PubMed Central

Giridharan, Nappan Veettil

2012-01-01

Purpose Obesity is a major public health problem worldwide, and of late, epidemiological studies indicate a preponderance of cataracts under obesity conditions. Although cataract is a multifactorial disorder and various biochemical mechanisms have been proposed, the influence of obesity on cataractogenesis has yet to be investigated. In such a scenario, a suitable animal model that develops cataract following the onset of obesity will be a welcome tool for biomedical research. Therefore, we investigated the molecular and biochemical basis for predisposition to cataract in the obese mutant rat models established in our institute because 15%–20% of these rats develop cataracts spontaneously as they reach 12–15 months of age. Methods We analyzed the major biochemical pathways in the normal lenses of different age groups of our obese mutant rat strains, Wistar/Obese (WNIN/Ob) and WNIN/GR-Ob, the former with euglycemia and the latter with an additional impaired glucose tolerance trait. In addition, sorbitol levels were estimated in the cataractous lenses of the obese rats. Results Except for the polyol pathway, all the principal pathways of the lens remained unaltered. Therefore, sorbitol levels were found to be high in the normal eye lenses of obese rats (WNIN/Ob and WNIN/GR-Ob) compared to their lean controls from three months of age onwards. Between WNIN/Ob and WNIN/GR-Ob, the levels of sorbitol were higher in the latter, suggesting a synergistic effect of impaired glucose tolerance along with obesity in the activation of the sorbitol pathway. Either way, an elevated sorbitol pathway seemed to be the predisposing factor responsible for cataract formation in these mutant rats. Conclusions Activation of the sorbitol pathway indeed enhances the risk of cataract development in conditions such as metabolic syndrome. These rat models thus may be valuable tools for investigating obesity-associated cataract and for developing intervention strategies, based on these findings. PMID:22393276

Activation of sorbitol pathway in metabolic syndrome and increased susceptibility to cataract in Wistar-Obese rats.

PubMed

Reddy, Paduru Yadagiri; Giridharan, Nappan Veettil; Reddy, Geereddy Bhanuprakash

2012-01-01

Obesity is a major public health problem worldwide, and of late, epidemiological studies indicate a preponderance of cataracts under obesity conditions. Although cataract is a multifactorial disorder and various biochemical mechanisms have been proposed, the influence of obesity on cataractogenesis has yet to be investigated. In such a scenario, a suitable animal model that develops cataract following the onset of obesity will be a welcome tool for biomedical research. Therefore, we investigated the molecular and biochemical basis for predisposition to cataract in the obese mutant rat models established in our institute because 15%-20% of these rats develop cataracts spontaneously as they reach 12-15 months of age. We analyzed the major biochemical pathways in the normal lenses of different age groups of our obese mutant rat strains, Wistar/Obese (WNIN/Ob) and WNIN/GR-Ob, the former with euglycemia and the latter with an additional impaired glucose tolerance trait. In addition, sorbitol levels were estimated in the cataractous lenses of the obese rats. Except for the polyol pathway, all the principal pathways of the lens remained unaltered. Therefore, sorbitol levels were found to be high in the normal eye lenses of obese rats (WNIN/Ob and WNIN/GR-Ob) compared to their lean controls from three months of age onwards. Between WNIN/Ob and WNIN/GR-Ob, the levels of sorbitol were higher in the latter, suggesting a synergistic effect of impaired glucose tolerance along with obesity in the activation of the sorbitol pathway. Either way, an elevated sorbitol pathway seemed to be the predisposing factor responsible for cataract formation in these mutant rats. Activation of the sorbitol pathway indeed enhances the risk of cataract development in conditions such as metabolic syndrome. These rat models thus may be valuable tools for investigating obesity-associated cataract and for developing intervention strategies, based on these findings.

RiboFACSeq: A new method for investigating metabolic and transport pathways in bacterial cells by combining a riboswitch-based sensor, fluorescence-activated cell sorting and next-generation sequencing

PubMed Central

Li, Yingfu

2017-01-01

The elucidation of the cellular processes involved in vitamin and cofactor biosynthesis is a challenging task. The conventional approaches to these investigations rely on the discovery and purification of the products (i.e proteins and metabolites) of a particular transport or biosynthetic pathway, prior to their subsequent analysis. However, the purification of low-abundance proteins or metabolites is a formidable undertaking that presents considerable technical challenges. As a solution, we present an alternative approach to such studies that circumvents the purification step. The proposed approach takes advantage of: (1) the molecular detection capabilities of a riboswitch-based sensor to detect the cellular levels of its cognate molecule, as a means to probe the integrity of the transport and biosynthetic pathways of the target molecule in cells, (2) the high-throughput screening ability of fluorescence-activated cell sorters to isolate cells in which only these specific pathways are disrupted, and (3) the ability of next-generation sequencing to quickly identify the genes of the FACS-sorted populations. This approach was named “RiboFACSeq”. Following their identification by RiboFACSeq, the role of these genes in the presumed pathway needs to be verified through appropriate functional assays. To demonstrate the utility of our approach, an adenosylcobalamin (AdoCbl)-responsive riboswitch-based sensor was used in this study to demonstrate that RiboFACSeq can be used to track and sort cells carrying genetic mutations in known AdoCbl transport and biosynthesis genes with desirable sensitivity and specificity. This method could potentially be used to elucidate any pathway of interest, as long as a suitable riboswitch-based sensor can be created. We believe that RiboFACSeq would be especially useful for the elucidation of biological pathways in which the proteins and/or their metabolites are present at very low physiological concentrations in cells, as is the case with vitamin and cofactor biosynthesis. PMID:29211762

The effect of pulmonary hypertension on ovine tricuspid annular dynamics.

PubMed

Malinowski, Marcin; Wilton, Penny; Khaghani, Asghar; Langholz, David; Hooker, Victoria; Eberhart, Lenora; Hooker, Robert L; Timek, Tomasz A

2016-01-01

Pulmonary hypertension (PHT) is associated with tricuspid annular dilatation, but the effect of acute increase of pulmonary pressure on three-dimensional (3D) tricuspid annular dynamics and shape is unknown. Better understanding of tricuspid annular dynamics may lead to improved and more durable surgical reparative techniques. In nine open-chest anaesthetized sheep nine sonomicrometry crystals were implanted on the right ventricle while on cardiopulmonary bypass. Additional nine crystals were implanted around the tricuspid annulus (TA) with one crystal at each commissure defining three separate annular regions: anterior, posterior and septal. Two additional equidistant crystals were implanted between each commissure, creating three segments for every region. Pressure transducers were placed in the left ventricular (LV), right ventricular (RV) and right atrium. PHT was induced by acute pulmonary artery constriction with a pneumatic occluder. Sonomicrometry and echocardiographic data were collected before and after induction of PHT. TA area, regional and total perimeter, and 3D annular geometry were calculated from 3D crystal coordinates. Regional annular contraction was defined as the percentage difference between maximal and minimal region length during the cardiac cycle. PHT increased RV pressure from 31 ± 9 mmHg to 46 ± 13 mmHg (P = 0.001) and decreased left ventricular (LV) pressure from 111 ± 24 mmHg to 78 ± 36 mmHg (P = 0.018). There was no significant tricuspid regurgitation observed with PHT. During PHT, the TA area increased by 12 ± 13% from 641 ± 139 mm(2) to 721 ± 177 mm(2) (P = 0.037). The total perimeter increased from 103 ± 11 mm to 109 ± 13 mm (P = 0.02). All annular regions dilated significantly with PHT with 8 ± 10, 5 ± 5 and 5 ± 5% increase in anterior, posterior and septal annular length, respectively (P < 0.05). PHT reduced regional annular contraction in the anterior region only (17 ± 7 vs 14 ± 8%; P = 0.02). The TA had a complex 3D saddle geometry and the shape of the annulus was altered during PHT only in the antero-posterior region. The changes in tricuspid annular conformation, contractility and its 3D geometry observed during acute ovine PHT may help in the design of new pathology-specific tricuspid annular rings. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Threats to North American forests from southern pine beetle with warming winters

NASA Astrophysics Data System (ADS)

Lesk, Corey; Coffel, Ethan; D'Amato, Anthony W.; Dodds, Kevin; Horton, Radley

2017-10-01

In coming decades, warmer winters are likely to ease range constraints on many cold-limited forest insects. Recent unprecedented expansion of the southern pine beetle (SPB, Dendroctonus frontalis) into New Jersey, New York and Connecticut in concert with warming annual temperature minima highlights the risk that this insect pest poses to the pine forests of the northern United States and Canada under continued climate change. Here we present projections of northward expansion in SPB-suitable climates using a statistical bioclimatic range modelling approach and current-generation general circulation model output under Representative Concentration Pathways 4.5 and 8.5. Results show that by the middle of the twenty-first century, the climate is likely to be suitable for SPB expansion into vast areas of previously unaffected forests throughout the northeastern United States and into southeastern Canada. This scenario would pose a significant economic and ecological risk to the affected regions, including disruption of local ecosystem services, shifts in forest structure, and threats to native biodiversity.

Compositional insights and valorization pathways for carbonaceous material deposited during bio-oil thermal treatment.

PubMed

Ochoa, Aitor; Aramburu, Borja; Ibáñez, María; Valle, Beatriz; Bilbao, Javier; Gayubo, Ana G; Castaño, Pedro

2014-09-01

This work analyses the composition, morphology, and thermal behavior of the carbonaceous materials deposited during the thermal treatment of bio-oil (thermal pyrolytic lignin-TPL). The bio-oil was obtained by flash pyrolysis of lignocellulosic biomass (pine sawdust), and the TPLs were obtained in the 400-700 °C range. The TPLs were characterized by performing elemental analysis; (13)C NMR, Raman, FTIR, and X-ray photoelectron spectroscopy; SEM; and temperature-programmed oxidation analyzed by differential thermogravimetry and differential scanning calorimetry. The results are compared to a commercial lignin (CL). The TPLs have lower oxygen and hydrogen contents and a greater aromaticity and structural order than the CL material. Based on these features, different valorization routes are proposed: the TPL obtained at 500 °C is suitable for use as a fuel, and the TPL obtained at 700 °C has a suitable morphology and composition for use as an adsorbent or catalyst support. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Morpho-histology and genotype dependence of in vitro morphogenesis in mature embryo cultures of wheat.

PubMed

Delporte, Fabienne; Pretova, Anna; du Jardin, Patrick; Watillon, Bernard

2014-11-01

Cellular totipotency is one of the basic principles of plant biotechnology. Currently, the success of the procedure used to produce transgenic plants is directly proportional to the successful insertion of foreign DNA into the genome of suitable target tissue/cells that are able to regenerate plants. The mature embryo (ME) is increasingly recognized as a valuable explant for developing regenerable cell lines in wheat biotechnology. We have previously developed a regeneration procedure based on fragmented ME in vitro culture. Before we can use this regeneration system as a model for molecular studies of the morphogenic pathway induced in vitro and investigate the functional links between regenerative capacity and transformation receptiveness, some questions need to be answered. Plant regeneration from cultured tissues is genetically controlled. Factors such as age/degree of differentiation and physiological conditions affect the response of explants to culture conditions. Plant regeneration in culture can be achieved through embryogenesis or organogenesis. In this paper, the suitability of ME tissues for tissue culture and the chronological series of morphological data observed at the macroscopic level are documented. Genetic variability at each step of the regeneration process was evaluated through a varietal comparison of several elite wheat cultivars. A detailed histological analysis of the chronological sequence of morphological events during ontogeny was conducted. Compared with cultures of immature zygotic embryos, we found that the embryogenic pathway occurs slightly earlier and is of a different origin in our model. Cytological, physiological, and some biochemical aspects of somatic embryo formation in wheat ME culture are discussed.

Assessment of two nonnative poeciliid fishes for monitoring selenium exposure in the endangered desert pupfish

USGS Publications Warehouse

Saiki, Michael K.; Martin, Barbara A.; May, Thomas W.; Brumbaugh, William G.

2012-01-01

We assessed the suitability of two nonnative poeciliid fishes—western mosquitofish (Gambusia affinis) and sailfin mollies (Poecilia latipinna)—for monitoring selenium exposure in desert pupfish (Cyprinodon macularius). Our investigation was prompted by a need to avoid lethal take of an endangered species (pupfish) when sampling fish for chemical analysis. Total selenium (SeTot) concentrations in both poeciliids were highly correlated with SeTot concentrations in pupfish. However, mean SeTot concentrations varied among fish species, with higher concentrations measured in mosquitofish than in mollies and pupfish from one of three sampled agricultural drains. Moreover, regression equations describing the relationship of selenomethionine to SeTot differed between mosquitofish and pupfish, but not between mollies and pupfish. Because selenium accumulates in animals primarily through dietary exposure, we examined fish trophic relationships by measuring stable isotopes (δ13C and δ15N) and gut contents. According to δ13C measurements, the trophic pathway leading to mosquitofish was more carbon-depleted than trophic pathways leading to mollies and pupfish, suggesting that energy flow to mosquitofish originated from allochthonous sources (terrestrial vegetation, emergent macrophytes, or both), whereas energy flow to mollies and pupfish originated from autochthonous sources (filamentous algae, submerged macrophytes, or both). The δ15N measurements indicated that mosquitofish and mollies occupied similar trophic levels, whereas pupfish occupied a slightly higher trophic level. Analysis of gut contents showed that mosquitofish consumed mostly winged insects (an indication of terrestrial taxa), whereas mollies and pupfish consumed mostly organic detritus. Judging from our results, only mollies (not mosquitofish) are suitable for monitoring selenium exposure in pupfish.

New methods for clinical pathways-Business Process Modeling Notation (BPMN) and Tangible Business Process Modeling (t.BPM).

PubMed

Scheuerlein, Hubert; Rauchfuss, Falk; Dittmar, Yves; Molle, Rüdiger; Lehmann, Torsten; Pienkos, Nicole; Settmacher, Utz

2012-06-01

Clinical pathways (CP) are nowadays used in numerous institutions, but their real impact is still a matter of debate. The optimal design of a clinical pathway remains unclear and is mainly determined by the expectations of the individual institution. The purpose of the here described pilot project was the development of two CP (colon and rectum carcinoma) according to Business Process Modeling Notation (BPMN) and Tangible Business Process Modeling (t.BPM). BPMN is an established standard for business process modelling in industry and economy. It is, in the broadest sense, a computer programme which enables the description and a relatively easy graphical imaging of complex processes. t.BPM is a modular construction system of the BPMN symbols which enables the creation of an outline or raw model, e.g. by placing the symbols on a spread-out paper sheet. The thus created outline can then be transferred to the computer and further modified as required. CP for the treatment of colon and rectal cancer have been developed with support of an external IT coach. The pathway was developed in an interdisciplinary and interprofessional manner (55 man-days over 15 working days). During this time, necessary interviews with medical, nursing and administrative staffs were conducted as well. Both pathways were developed parallel. Subsequent analysis was focussed on feasibility, expenditure, clarity and suitability for daily clinical practice. The familiarization with BPMN was relatively quick and intuitive. The use of t.BPM enabled the pragmatic, effective and results-directed creation of outlines for the CP. The development of both CP was finished from the diagnostic evaluation to the adjuvant/neoadjuvant therapy and rehabilitation phase. The integration of checklists, guidelines and important medical or other documents is easily accomplished. A direct integration into the hospital computer system is currently not possible for technical reasons. BPMN and t.BPM are sufficiently suitable for the planned modelling and imaging of CP. The application in medicine is new, and transfer from the industrial process management is in principle possible. BPMN-CP may be used for teaching and training, patient information and quality management. The graphical image is clearly structured and appealing. Even though the efficiency in the creation of BPMN-CP increases markedly after the training phase, high amounts of manpower and time are required. The most sensible and consequent application of a BPMN-CP would be the direct integration into the hospital computer system. The integration of a modelling language, such as BPMN, into the hospital computer systems could be a very sensible approach for the development of new hospital information systems in the future.

Molecularly imprinted polymers as a tool for the study of the 4-ethylphenol metabolic pathway in red wines.

PubMed

Garcia, Deiene; Gomez-Caballero, Alberto; Guerreiro, Antonio; Goicolea, M Aranzazu; Barrio, Ramon J

2015-09-04

A molecularly imprinted polymer (MIP) based methodology is described here for the determination of compounds that belong to the 4-ethylphenol (4EP) metabolic pathway in red wines. To this end, two MIP materials have been developed: a 4EP MIP as a class-selective material to extract phenols that belong to the 4EP metabolic pathway and a coumaric acid (CA) imprinted polymer as a MIP-based stationary phase capable of selectively separating these phenols on HPLC analysis, obtaining clean chromatograms. 4-vinyl pyridine and ethylene glycol dimethacrylate were respectively used as functional monomer and cross-linker for both MIPs. Once polymer compositions were optimised, the 4EP MIP was packed into SPE cartridges for wine sample clean-up and CA MIP was packed into HPLC columns to chromatographically separate the compounds present in the eluates obtained after SPE extraction. The accuracy of the proposed method was tested spiking wine samples with known concentrations of target compounds and subsequently, analytes were quantified by the standard addition method. Registered mean recoveries ranged from 95.2 to 109.2% and RSD values were below 10% in most cases. The described methodology was found to be suitable for the selective extraction and quantification of the compounds that belong to the 4EP metabolic pathway in red wines with minimal matrix effects and could be undoubtedly exploited to monitor 4EP and its precursors in wines. Copyright © 2015 Elsevier B.V. All rights reserved.

Plasma metabonomics study of the patients with acute anterior uveitis based on ultra-performance liquid chromatography-mass spectrometry.

PubMed

Guo, Junguo; Yan, Tingqin; Bi, Hongsheng; Xie, Xiaofeng; Wang, Xingrong; Guo, Dadong; Jiang, Haiqiang

2014-06-01

The identification of the biomarkers of patients with acute anterior uveitis (AAU) may allow for a less invasive and more accurate diagnosis, as well as serving as a predictor in AAU progression and treatment response. The aim of this study was to identify the potential biomarkers and the metabolic pathways from plasma in patients with AAU. Both plasma metabolic biomarkers and metabolic pathways in the AAU patients versus healthy volunteers were investigated using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and a metabonomics approach. The principal component analysis (PCA) was used to separate AAU patients from healthy volunteers as well as to identify the different biomarkers between the two groups. Metabolic compounds were matched to the KEGG, METLIN, and HMDB databases, and metabolic pathways associated with AAU were identified. The PCA for UPLC-MS data shows that the metabolites in AAU patients were significantly different from those of healthy volunteers. Of the 4,396 total features detected by UPLC-MS, 102 features were significantly different between AAU patients and healthy volunteers according to the variable importance plot (VIP) values (greater than two) of partial least squares discriminate analysis (PLS-DA). Thirty-three metabolic compounds were identified and were considered as potential biomarkers. Meanwhile, ten metabolic pathways were found that were related to the AAU according to the identified biomarkers. These data suggest that metabolomics study can identify potential metabolites that differ between AAU patients and healthy volunteers. Based on the PCA, PLS-DA, several potential metabolic biomarkers and pathways in AAU patients were found and identified. In addition, the UPLC-MS technique combined with metabonomics could be a suitable systematic biology tool in research in clinical problems in ophthalmology, and can provide further insight into the pathophysiology of AAU.

Metabolomic profiling and genomic analysis of wheat aneuploid lines to identify genes controlling biochemical pathways in mature grain.

PubMed

Francki, Michael G; Hayton, Sarah; Gummer, Joel P A; Rawlinson, Catherine; Trengove, Robert D

2016-02-01

Metabolomics is becoming an increasingly important tool in plant genomics to decipher the function of genes controlling biochemical pathways responsible for trait variation. Although theoretical models can integrate genes and metabolites for trait variation, biological networks require validation using appropriate experimental genetic systems. In this study, we applied an untargeted metabolite analysis to mature grain of wheat homoeologous group 3 ditelosomic lines, selected compounds that showed significant variation between wheat lines Chinese Spring and at least one ditelosomic line, tracked the genes encoding enzymes of their biochemical pathway using the wheat genome survey sequence and determined the genetic components underlying metabolite variation. A total of 412 analytes were resolved in the wheat grain metabolome, and principal component analysis indicated significant differences in metabolite profiles between Chinese Spring and each ditelosomic lines. The grain metabolome identified 55 compounds positively matched against a mass spectral library where the majority showed significant differences between Chinese Spring and at least one ditelosomic line. Trehalose and branched-chain amino acids were selected for detailed investigation, and it was expected that if genes encoding enzymes directly related to their biochemical pathways were located on homoeologous group 3 chromosomes, then corresponding ditelosomic lines would have a significant reduction in metabolites compared with Chinese Spring. Although a proportion showed a reduction, some lines showed significant increases in metabolites, indicating that genes directly and indirectly involved in biosynthetic pathways likely regulate the metabolome. Therefore, this study demonstrated that wheat aneuploid lines are suitable experimental genetic system to validate metabolomics-genomics networks. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Spatial Extent of Charge Repulsion Regulates Assembly Pathways for Lysozyme Amyloid Fibrils

PubMed Central

Hill, Shannon E.; Miti, Tatiana; Richmond, Tyson; Muschol, Martin

2011-01-01

Formation of large protein fibrils with a characteristic cross β-sheet architecture is the key indicator for a wide variety of systemic and neurodegenerative amyloid diseases. Recent experiments have strongly implicated oligomeric intermediates, transiently formed during fibril assembly, as critical contributors to cellular toxicity in amyloid diseases. At the same time, amyloid fibril assembly can proceed along different assembly pathways that might or might not involve such oligomeric intermediates. Elucidating the mechanisms that determine whether fibril formation proceeds along non-oligomeric or oligomeric pathways, therefore, is important not just for understanding amyloid fibril assembly at the molecular level but also for developing new targets for intervening with fibril formation. We have investigated fibril formation by hen egg white lysozyme, an enzyme for which human variants underlie non-neuropathic amyloidosis. Using a combination of static and dynamic light scattering, atomic force microscopy and circular dichroism, we find that amyloidogenic lysozyme monomers switch between three different assembly pathways: from monomeric to oligomeric fibril assembly and, eventually, disordered precipitation as the ionic strength of the solution increases. Fibril assembly only occurred under conditions of net repulsion among the amyloidogenic monomers while net attraction caused precipitation. The transition from monomeric to oligomeric fibril assembly, in turn, occurred as salt-mediated charge screening reduced repulsion among individual charged residues on the same monomer. We suggest a model of amyloid fibril formation in which repulsive charge interactions are a prerequisite for ordered fibril assembly. Furthermore, the spatial extent of non-specific charge screening selects between monomeric and oligomeric assembly pathways by affecting which subset of denatured states can form suitable intermolecular bonds and by altering the energetic and entropic requirements for the initial intermediates emerging along the monomeric vs. oligomeric assembly path. PMID:21483680

A Theoretical Study of 8-Chloro-9-Hydroxy-Aflatoxin B₁, the Conversion Product of Aflatoxin B₁ by Neutral Electrolyzed Water.

PubMed

Escobedo-González, René; Méndez-Albores, Abraham; Villarreal-Barajas, Tania; Aceves-Hernández, Juan Manuel; Miranda-Ruvalcaba, René; Nicolás-Vázquez, Inés

2016-07-21

Theoretical studies of 8-chloro-9-hydroxy-aflatoxin B₁ (2) were carried out by Density Functional Theory (DFT). This molecule is the reaction product of the treatment of aflatoxin B₁ (1) with hypochlorous acid, from neutral electrolyzed water. Determination of the structural, electronic and spectroscopic properties of the reaction product allowed its theoretical characterization. In order to elucidate the formation process of 2, two reaction pathways were evaluated-the first one considering only ionic species (Cl⁺ and OH(-)) and the second one taking into account the entire hypochlorous acid molecule (HOCl). Both pathways were studied theoretically in gas and solution phases. In the first suggested pathway, the reaction involves the addition of chlorenium ion to 1 forming a non-classic carbocation assisted by anchimeric effect of the nearest aromatic system, and then a nucleophilic attack to the intermediate by the hydroxide ion. In the second studied pathway, as a first step, the attack of the double bond from the furanic moiety of 1 to the hypochlorous acid is considered, accomplishing the same non-classical carbocation, and again in the second step, a nucleophilic attack by the hydroxide ion. In order to validate both reaction pathways, the atomic charges, the highest occupied molecular orbital and the lowest unoccupied molecular orbital were obtained for both substrate and product. The corresponding data imply that the C₉ atom is the more suitable site of the substrate to interact with the hydroxide ion. It was demonstrated by theoretical calculations that a vicinal and anti chlorohydrin is produced in the terminal furan ring. Data of the studied compound indicate an important reduction in the cytotoxic and genotoxic potential of the target molecule, as demonstrated previously by our research group using different in vitro assays.

Spatio-temporal Assessment Of The Land Use Implications Of Solar PV And Bioenergy Deployment In The UK TM Energy Model

NASA Astrophysics Data System (ADS)

Sobral Mourao, Z.; Konadu, D. D.; Skelton, S.; Lupton, R.

2015-12-01

The UK TIMES model (UKTM) succeeds the UK MARKAL as the underlying model of the UK Department of Energy and Climate Change (DECC) for long term energy system planning and policy development. It generates energy system pathways which achieve the 80% greenhouse gas (GHG) emissions reduction target by 2050, stipulated in the UK Climate Change Act (2008), at the least possible cost. Some of these pathways prescribe large-scale deployment of solar PV and indigenously sourced bioenergy, which are land intensive and could result in significant land use transitions; but would this create competition and stress for UK land use? To answer the above question, this study uses an integrated spatio-temporal modelling approach, ForeseerTM, which characterises the interdependencies between the energy and land systems by evaluating the land required under each pathways for solar PV and bioenergy, based on scenarios of a range of PV conversion efficiencies, and energy crop yield projections. The outcome is compared with availability of suitable locations for solar PV and sustainable limits of agricultural land appropriation for bioenergy production to assess potential stresses and competition with other land use services. Preliminary results show UKTM pathways could pose significant impact on the UK land use system. Bioenergy deployment could potentially compete with other land services by taking up a significant part of the available UK agricultural land thus competing directly with food production, most notably livestock production. For pathways with significant solar PV deployment, direct competition would not be focussed on the high quality land used for food crop production but rather for land used for livestock production and other ecosystem services.

Vancouver Transcatheter Aortic Valve Replacement Clinical Pathway: Minimalist Approach, Standardized Care, and Discharge Criteria to Reduce Length of Stay.

PubMed

Lauck, Sandra B; Wood, David A; Baumbusch, Jennifer; Kwon, Jae-Yung; Stub, Dion; Achtem, Leslie; Blanke, Philipp; Boone, Robert H; Cheung, Anson; Dvir, Danny; Gibson, Jennifer A; Lee, Bobby; Leipsic, Jonathan; Moss, Robert; Perlman, Gidon; Polderman, Jopie; Ramanathan, Krishnan; Ye, Jian; Webb, John G

2016-05-01

We describe the development, implementation, and evaluation of a standardized clinical pathway to facilitate safe discharge home at the earliest time after transfemoral transcatheter aortic valve replacement. Between May 2012 and October 2014, the Heart Team developed a clinical pathway suited to the unique requirements of transfemoral transcatheter aortic valve replacement in contemporary practice. The components included risk-stratified minimalist periprocedure approach, standardized postprocedure care with early mobilization and reconditioning, and criteria-driven discharge home. Our aim was to reduce variation in care, identify a subgroup of patients suitable for early discharge (≤48 hours), and decrease length of stay for all patients. We addressed barriers related to historical practices, complex multidisciplinary stakeholder engagement, and adoption of length of stay as a quality indicator. We retrospectively reviewed the experiences of 393 consecutive patients; 150 (38.2%) were discharged early. At baseline, early discharge patients had experienced less previous balloon aortic valvuloplasty, had higher left ventricular ejection fraction, better cognitive function, and were less frail than the standard discharge group (>48 hours). Early discharge was associated with the use of local anesthesia, implantation of balloon expandable device, avoidance of urinary catheter, and early removal of temporary pacemaker. Median length of stay was 1 day for early discharge and 3 days for other patients; 97.7% were discharged home. There were no differences in 30-day mortality (1.3%), disabling stroke (0.8%), or readmission (10.7%). The implementation of a transcatheter aortic valve replacement clinical pathway shifted the program's approach to combine standardized processes and individual risk stratification. The Vancouver transcatheter aortic valve replacement clinical pathway requires a rigorous assessment to determine its efficacy, safety, and reproducibility. © 2016 American Heart Association, Inc.

Chemical modification and degradation of atrazine in Medicago sativa through multiple pathways.

PubMed

Zhang, Jing Jing; Lu, Yi Chen; Yang, Hong

2014-10-08

Atrazine is a member of the triazine herbicide family intensively used to control weeds for crop production. In this study, atrazine residues and its degraded products in alfalfa (Medicago sativa) were characterized using UPLC-TOF-MS/MS. Most of atrazine absorbed in plants was found as chemically modified derivatives like deisopropylated atrazine (DIA), dehydrogenated atrazine (DHA), or methylated atrazine (MEA), and some atrazine derivatives were conjugated through different functional groups such as sugar, glutathione, and amino acids. Interestingly, the specific conjugates DHA+hGSH (homoglutathione) and MEA-HCl+hGSH in alfalfa were detected. These results suggest that atrazine in alfalfa can be degraded through different pathways. The increased activities of glycosyltransferase and glutathione S-transferase were determined to support the atrazine degradation models. The outcome of the work uncovered the detailed mechanism for the residual atrazine accumulation and degradation in alfalfa and will help to evaluate whether the crop is suitable to be cultivated in the atrazine-polluted soil.

Signalling and chemosensitivity assays in melanoma: is mutated status a prerequisite for targeted therapy?

PubMed

Passeron, Thierry; Lacour, Jean-Philippe; Allegra, Maryline; Ségalen, Coralie; Deville, Anne; Thyss, Antoine; Giacchero, Damien; Ortonne, Jean-Paul; Bertolotto, Corine; Ballotti, Robert; Bahadoran, Philippe

2011-12-01

Selection for targeted therapies in melanoma is currently based on the search for mutations in selected genes. We aimed at evaluating the interest of signalling and chemosensitivity studies in addition to genotyping for assessing the best suitable treatment in an individual patient. We extracted genomic DNA and melanoma cells from tumor tissue of a skin metastasis of a 17-year-old woman with stage IV melanoma progressing despite three successive lines of treatment. Despite the absence of mutation in BRAF, NRAS cKIT, the MAPK pathway was activated and a significant response to sorafenib, a mitogen-activated protein kinase (MAPK)/RAF inhibitor, was found in signalling and chemosensitivity assays. A treatment combining sorafenib and dacarbazine produced a partial response for 9 months, with marked necrosis in some lesions. Chemosensitivity assays and signalling pathway studies could be of great value in addition to genotyping for assessing the most appropriate treatment in melanoma. © 2011 John Wiley & Sons A/S.

An optimized whole blood assay measuring expression and activity of NLRP3, NLRC4 and AIM2 inflammasomes.

PubMed

Grinstein, Lev; Endter, Kristin; Hedrich, Christian M; Reinke, Sören; Luksch, Hella; Schulze, Felix; Robertson, Avril A B; Cooper, Matthew A; Rösen-Wolff, Angela; Winkler, Stefan

2018-06-01

The proinflammatory protease caspase-1 plays pivotal roles in central pathways of innate immunity, thereby contributing to pathogen clearance. Beside its physiological role, dysregulated activity of caspase-1 is known to contribute to an increasing number of diseases. In this study, we optimized and validated a low-volume human whole blood assay facilitating the measurement of caspase-1 activation and inflammasome-related gene expression upon stimulation of the NLRP3, NLRC4 or AIM2 inflammasome. Using the NLRP3 inflammasome specific inhibitor MCC950, we were able to measure the activity of canonical or alternative NLRP3 pathways, AIM2 and NLRC4 inflammasomes in whole blood. Based on our data we assume a superposition of NLRP3 and NLRC4 inflammasome activities in human whole blood following stimulation with S. typhimurium. The optimized whole blood assay may be suitable for diagnostic and research purposes for pediatric patients who can only donate small amounts of blood. Copyright © 2017 Elsevier Inc. All rights reserved.

A systematic evaluation of the potential effects of trichloroethylene exposure on cardiac development.

PubMed

Makris, Susan L; Scott, Cheryl Siegel; Fox, John; Knudsen, Thomas B; Hotchkiss, Andrew K; Arzuaga, Xabier; Euling, Susan Y; Powers, Christina M; Jinot, Jennifer; Hogan, Karen A; Abbott, Barbara D; Hunter, E Sidney; Narotsky, Michael G

2016-10-01

The 2011 EPA trichloroethylene (TCE) IRIS assessment, used developmental cardiac defects from a controversial drinking water study in rats (Johnson et al. [51]), along with several other studies/endpoints to derive reference values. An updated literature search of TCE-related developmental cardiac defects was conducted. Study quality, strengths, and limitations were assessed. A putative adverse outcome pathway (AOP) construct was developed to explore key events for the most commonly observed cardiac dysmorphologies, particularly those involved with epithelial-mesenchymal transition (EMT) of endothelial origin (EndMT); several candidate pathways were identified. A hypothesis-driven weight-of-evidence analysis of epidemiological, toxicological, in vitro, in ovo, and mechanistic/AOP data concluded that TCE has the potential to cause cardiac defects in humans when exposure occurs at sufficient doses during a sensitive window of fetal development. The study by Johnson et al. [51] was reaffirmed as suitable for hazard characterization and reference value derivation, though acknowledging study limitations and uncertainties. Published by Elsevier Inc.

The Westgate Service and Related Referral, Assessment, and Treatment Processes.

PubMed

Bennett, Alice L

2015-12-01

The formerly named "Dangerous and Severe Personality Disorder" (DSPD) units are no longer standalone services within the criminal justice system in England and Wales. These sites now provide personality disorder treatment services in the high-security prison estate as part of the new national Offender Personality Disorder (OPD) Pathway Strategy. The OPD Pathway intends to take responsibility for the assessment, treatment, and management of offenders who are likely to have a personality disorder and who present a high risk of re-offending (men and women) and serious harm to others (men). Further PD treatment and progression services are being commissioned in lower security prisons and in the community as part of the new PD Strategy. While the suitability criteria for the two male high-security PD treatment sites are the same, the individual units have their own assessment and treatment methods. This article aims to communicate the referral, assessment, and treatment methods employed within the prison-based Westgate Personality Disorder Treatment Service, HMP Frankland. © The Author(s) 2014.

System-based strategies for p53 recovery.

PubMed

Azam, Muhammad Rizwan; Fazal, Sahar; Ullah, Mukhtar; Bhatti, Aamer I

2018-06-01

The authors have proposed a systems theory-based novel drug design approach for the p53 pathway. The pathway is taken as a dynamic system represented by ordinary differential equations-based mathematical model. Using control engineering practices, the system analysis and subsequent controller design is performed for the re-activation of wild-type p53. p53 revival is discussed for both modes of operation, i.e. the sustained and oscillatory. To define the problem in control system paradigm, modification in the existing mathematical model is performed to incorporate the effect of Nutlin. Attractor point analysis is carried out to select the suitable domain of attraction. A two-loop negative feedback control strategy is devised to drag the system trajectories to the attractor point and to regulate cellular concentration of Nutlin, respectively. An integrated framework is constituted to incorporate the pharmacokinetic effects of Nutlin in the cancerous cells. Bifurcation analysis is also performed on the p53 model to see the conditions for p53 oscillation.

Metabolic engineering of microorganisms for the synthesis of plant natural products.

PubMed

Marienhagen, Jan; Bott, Michael

2013-01-20

Of more than 200,000 plant natural products known to date, many demonstrate important pharmacological activities or are of biotechnological significance. However, isolation from natural sources is usually limited by low abundance and environmental, seasonal as well as regional variation, whereas total chemical synthesis is typically commercially unfeasible considering the complex structures of most plant natural products. With advances in DNA sequencing and recombinant DNA technology many of the biosynthetic pathways responsible for the production of these valuable compounds have been elucidated, offering the opportunity of a functional integration of biosynthetic pathways in suitable microorganisms. This approach offers promise to provide sufficient quantities of the desired plant natural products from inexpensive renewable resources. This review covers recent advancements in the metabolic engineering of microorganisms for the production of plant natural products such as isoprenoids, phenylpropanoids and alkaloids, and highlights general approaches and strategies to gain access to the rich biochemical diversity of plants by employing the biosynthetic power of microorganisms. Copyright © 2012 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Chen; Perez, Danny; Voter, Arthur F.

Hyperdynamics is a powerful method to significantly extend the time scales amenable to molecular dynamics simulation of infrequent events. One outstanding challenge, however, is the development of the so-called bias potential required by the method. In this work, we design a bias potential using information about all minimum energy pathways (MEPs) out of the current state. While this approach is not suitable for use in an actual hyperdynamics simulation, because the pathways are generally not known in advance, it allows us to show that it is possible to come very close to the theoretical boost limit of hyperdynamics while maintainingmore » high accuracy. We demonstrate this by applying this MEP-based hyperdynamics (MEP-HD) to metallic surface diffusion systems. In most cases, MEP-HD gives boost factors that are orders of magnitude larger than the best existing bias potential, indicating that further development of hyperdynamics bias potentials could have a significant payoff. Lastly, we discuss potential practical uses of MEP-HD, including the possibility of developing MEP-HD into a true hyperdynamics.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mogi, Makio, E-mail: makio@dpc.aichi-gakuin.ac.jp; Kondo, Ayami

Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor regulates bone mass by inhibiting osteoclastic bone resorption. mTOR, which is the mammalian target of rapamycin, is a kinase and central regulator of cell growth, proliferation, and survival. By using Rapamycin, we studied whether mTOR pathway is associated with OPG protein production in the mouse bone marrow-derived stromal cell line ST2. Rapamycin markedly increased the level of soluble OPG in ST2 cells. This antibiotic treatment resulted in the suppression of phosphorylation of mTOR. Rapamycin had no effects on the proliferation, differentiation, or apoptosis of the cells. Treatment with bone morphogenetic protein-4, which can induce OPG proteinmore » in ST2 cells, also resulted in a decrease in the density of the phospho-mTOR-band, suggesting that the suppression of the phospho-mTOR pathway is necessary for OPG production in ST2 cells. Thus, suitable suppression of mTOR phosphorylation is a necessary requirement for OPG production in bone marrow stromal cells.« less

New trends in encapsulation of liposoluble vitamins.

PubMed

Gonnet, M; Lethuaut, L; Boury, F

2010-09-15

Liposoluble vitamins (A, D, E, and K) and carotenoids have many benefits on health. They are provided mainly by foods. At pharmacological doses, they can also be used to treat skin diseases, several types of cancer or decrease oxidative stress. These molecules are sensitive to oxidation, thus encapsulation might constitute an appropriate mean to preserve their properties during storage and enhance their physiological potencies. Formulation processes have been adapted for sensitive molecule, limiting their exposure to high temperature, light or oxygen. Each administration pathway, oral, systemic, topical, transdermal and local, requires different particle sizes and release profile. Encapsulation can lead to greater efficiency allowing smaller administration doses thus diminishing potential hypervitaminosis syndrome appearance and side effects. Carrier formulation can be based on vitamin dissolution in lipid media and its stabilization by surfactant mixture, on its entrapment in a matrix or molecular system. Suitability of each type of carrier will be discussed for each pathway. 2010 Elsevier B.V. All rights reserved.

Stem Cells in the Trabecular Meshwork for Regulating Intraocular Pressure.

PubMed

Yun, Hongmin; Zhou, Yi; Wills, Andrew; Du, Yiqin

2016-06-01

Intraocular pressure (IOP) is still the main treatment target for glaucoma. Outflow resistance mainly exists at the trabecular meshwork (TM) outflow pathway, which is responsible for IOP regulation. Changes of TM cellularity and TM extracellular matrix turnover may play important roles in IOP regulation. In this article, we review basic anatomy and physiology of the outflow pathway and TM stem cell characteristics regarding the location, isolation, identification and function. TM stem cells are localized at the insert region of the TM and are label-retaining in vivo. They can be isolated by side-population cell sorting, cloning culture, or sphere culture. TM stem cells are multipotent with the ability to home to the TM region and differentiate into TM cells in vivo. Other stem cell types, such as adipose-derived stem cells, mesenchymal stem cells and induced pluripotent stem cells have been discovered for TM cell differentiation and TM regeneration. We also review glaucomatous animal models, which are suitable to study stem cell-based therapies for TM regeneration.

Stem Cells in the Trabecular Meshwork for Regulating Intraocular Pressure

PubMed Central

Yun, Hongmin; Zhou, Yi; Wills, Andrew

2016-01-01

Abstract Intraocular pressure (IOP) is still the main treatment target for glaucoma. Outflow resistance mainly exists at the trabecular meshwork (TM) outflow pathway, which is responsible for IOP regulation. Changes of TM cellularity and TM extracellular matrix turnover may play important roles in IOP regulation. In this article, we review basic anatomy and physiology of the outflow pathway and TM stem cell characteristics regarding the location, isolation, identification and function. TM stem cells are localized at the insert region of the TM and are label-retaining in vivo. They can be isolated by side-population cell sorting, cloning culture, or sphere culture. TM stem cells are multipotent with the ability to home to the TM region and differentiate into TM cells in vivo. Other stem cell types, such as adipose-derived stem cells, mesenchymal stem cells and induced pluripotent stem cells have been discovered for TM cell differentiation and TM regeneration. We also review glaucomatous animal models, which are suitable to study stem cell-based therapies for TM regeneration. PMID:27183473

Engineered microorganisms capable of producing target compounds under anaerobic conditions

DOEpatents

Buelter, Thomas [Denver, CO; Meinhold, Peter [Denver, CO; Feldman, Reid M. Renny [San Francisco, CA; Hawkins, Andrew C [Parker, CO; Urano, Jun [Irvine, CA; Bastian, Sabine [Pasadena, CA; Arnold, Frances [La Canada, CA

2012-01-17

The present invention is generally provides recombinant microorganisms comprising engineered metabolic pathways capable of producing C3-C5 alcohols under aerobic and anaerobic conditions. The invention further provides ketol-acid reductoisomerase enzymes which have been mutated or modified to increase their NADH-dependent activity or to switch the cofactor preference from NADPH to NADH and are expressed in the modified microorganisms. In addition, the invention provides isobutyraldehyde dehydrogenase enzymes expressed in modified microorganisms. Also provided are methods of producing beneficial metabolites under aerobic and anaerobic conditions by contacting a suitable substrate with the modified microorganisms of the present invention.

Synthesis and Reactivity of Backfluorinated NHC Carbene Complexes (Briefing Charts)

DTIC Science & Technology

2015-07-01

Distribution A: Approved for public release 13 Preparation of Perfluoroalkyl Grignard Reagents F(CF2CF2)nCH2CH2I Mg, Et2O ref lux F(CF2CF2)nCH2CH2MgI F...Synthetic Method #1 Grignard Addition/Reduction/Cyclization • Very general reaction pathway: suitable for all Grignard reagents • Attempts at...dialkylation unsuccessful • Slight excess of Grignard reagent ensures complete monoalkylation N N MesMes N N MesMes F2 C MgX Et2O, rt N N MesMes CF2 MgX 2

A convenient method for preparation of 2-amino-4,6-diphenylnicotinonitrile using HBF4 as an efficient catalyst via an anomeric based oxidation: A joint experimental and theoretical study

NASA Astrophysics Data System (ADS)

Zolfigol, Mohammad Ali; Kiafar, Mahya; Yarie, Meysam; Taherpour, Avat(Arman); Fellowes, Thomas; Nicole Hancok, Amber; Yari, Ako

2017-06-01

Experimental and computational studies in the synthesis of 2-amino-4,6-diphenylnicotinonitrile using HBF4 as an oxidizing promoter catalyst under mild and solvent free conditions were carried out. The suggested anomeric based oxidation (ABO) mechanism is supported by experimental and theoretical evidence. The theoretical study shows that the intermediate isomers with 5R- and 5S- chiral positions have suitable structures for the aromatization through an anomeric based oxidation in the final step of the mechanistic pathway.

Climate Change, Northern Birds of Conservation Concern and Matching the Hotspots of Habitat Suitability with the Reserve Network

PubMed Central

Virkkala, Raimo; Heikkinen, Risto K.; Fronzek, Stefan; Leikola, Niko

2013-01-01

National reserve networks are one of the most important means of species conservation, but their efficiency may be diminished due to the projected climatic changes. Using bioclimatic envelope models and spatial data on habitats and conservation areas, we studied how efficient the reserve network will be in preserving 100 forest, mire, marshland, and alpine bird species of conservation concern in Finland in 2051–2080 under three different climate scenarios. The occurrences of the studied bird species were related to the amount of habitat preferred by each species in the different boreal zones. We employed a novel integrated habitat suitability index that takes into account both the species’ probability of occurrence from the bioclimatic models and the availability of suitable habitat. Using this suitability index, the distribution of the topmost 5% suitability squares (“hotspots”) in the four bird species groups in the period 1971–2000 and under the three scenarios were compared with the location of reserves with the highest amounts of the four habitats to study the efficiency of the network. In species of mires, marshlands, and Arctic mountains, a high proportion of protected habitat was included in the 5% hotspots in the scenarios in 2051–2080, showing that protected areas cover a high proportion of occurrences of bird species. In contrast, in forests in the southern and middle boreal zones, only a small proportion of the protected habitat was included in the 5% hotspots, indicating that the efficiency of the protected area network will be insufficient for forest birds in the future. In the northern boreal zone, the efficiency of the reserve network in forests was highly dependent on the strength of climate change varying between the scenarios. Overall, there is no single solution to preserving biodiversity in a changing climate, but several future pathways should be considered. PMID:23700420

Climate change likely to reduce orchid bee abundance even in climatic suitable sites.

PubMed

Faleiro, Frederico Valtuille; Nemésio, André; Loyola, Rafael

2018-06-01

Studies have tested whether model predictions based on species' occurrence can predict the spatial pattern of population abundance. The relationship between predicted environmental suitability and population abundance varies in shape, strength and predictive power. However, little attention has been paid to the congruence in predictions of different models fed with occurrence or abundance data, in particular when comparing metrics of climate change impact. Here, we used the ecological niche modeling fit with presence-absence and abundance data of orchid bees to predict the effect of climate change on species and assembly level distribution patterns. In addition, we assessed whether predictions of presence-absence models can be used as a proxy to abundance patterns. We obtained georeferenced abundance data of orchid bees (Hymenoptera: Apidae: Euglossina) in the Brazilian Atlantic Forest. Sampling method consisted in attracting male orchid bees to baits of at least five different aromatic compounds and collecting the individuals with entomological nets or bait traps. We limited abundance data to those obtained by similar standard sampling protocol to avoid bias in abundance estimation. We used boosted regression trees to model ecological niches and project them into six climate models and two Representative Concentration Pathways. We found that models based on species occurrences worked as a proxy for changes in population abundance when the output of the models were continuous; results were very different when outputs were discretized to binary predictions. We found an overall trend of diminishing abundance in the future, but a clear retention of climatically suitable sites too. Furthermore, geographic distance to gained climatic suitable areas can be very short, although it embraces great variation. Changes in species richness and turnover would be concentrated in western and southern Atlantic Forest. Our findings offer support to the ongoing debate of suitability-abundance models and can be used to support spatial conservation prioritization schemes and species triage in Atlantic Forest. © 2018 John Wiley & Sons Ltd.

Climate change, northern birds of conservation concern and matching the hotspots of habitat suitability with the reserve network.

PubMed

Virkkala, Raimo; Heikkinen, Risto K; Fronzek, Stefan; Leikola, Niko

2013-01-01

National reserve networks are one of the most important means of species conservation, but their efficiency may be diminished due to the projected climatic changes. Using bioclimatic envelope models and spatial data on habitats and conservation areas, we studied how efficient the reserve network will be in preserving 100 forest, mire, marshland, and alpine bird species of conservation concern in Finland in 2051-2080 under three different climate scenarios. The occurrences of the studied bird species were related to the amount of habitat preferred by each species in the different boreal zones. We employed a novel integrated habitat suitability index that takes into account both the species' probability of occurrence from the bioclimatic models and the availability of suitable habitat. Using this suitability index, the distribution of the topmost 5% suitability squares ("hotspots") in the four bird species groups in the period 1971-2000 and under the three scenarios were compared with the location of reserves with the highest amounts of the four habitats to study the efficiency of the network. In species of mires, marshlands, and Arctic mountains, a high proportion of protected habitat was included in the 5% hotspots in the scenarios in 2051-2080, showing that protected areas cover a high proportion of occurrences of bird species. In contrast, in forests in the southern and middle boreal zones, only a small proportion of the protected habitat was included in the 5% hotspots, indicating that the efficiency of the protected area network will be insufficient for forest birds in the future. In the northern boreal zone, the efficiency of the reserve network in forests was highly dependent on the strength of climate change varying between the scenarios. Overall, there is no single solution to preserving biodiversity in a changing climate, but several future pathways should be considered.

Climate suitability for European ticks: assessing species distribution models against null models and projection under AR5 climate.

PubMed

Williams, Hefin Wyn; Cross, Dónall Eoin; Crump, Heather Louise; Drost, Cornelis Jan; Thomas, Christopher James

2015-08-28

There is increasing evidence that the geographic distribution of tick species is changing. Whilst correlative Species Distribution Models (SDMs) have been used to predict areas that are potentially suitable for ticks, models have often been assessed without due consideration for spatial patterns in the data that may inflate the influence of predictor variables on species distributions. This study used null models to rigorously evaluate the role of climate and the potential for climate change to affect future climate suitability for eight European tick species, including several important disease vectors. We undertook a comparative assessment of the performance of Maxent and Mahalanobis Distance SDMs based on observed data against those of null models based on null species distributions or null climate data. This enabled the identification of species whose distributions demonstrate a significant association with climate variables. Latest generation (AR5) climate projections were subsequently used to project future climate suitability under four Representative Concentration Pathways (RCPs). Seven out of eight tick species exhibited strong climatic signals within their observed distributions. Future projections intimate varying degrees of northward shift in climate suitability for these tick species, with the greatest shifts forecasted under the most extreme RCPs. Despite the high performance measure obtained for the observed model of Hyalomma lusitanicum, it did not perform significantly better than null models; this may result from the effects of non-climatic factors on its distribution. By comparing observed SDMs with null models, our results allow confidence that we have identified climate signals in tick distributions that are not simply a consequence of spatial patterns in the data. Observed climate-driven SDMs for seven out of eight species performed significantly better than null models, demonstrating the vulnerability of these tick species to the effects of climate change in the future.

Global decline in suitable habitat for Angiostrongylus ( = Parastrongylus) cantonensis: the role of climate change.

PubMed

York, Emily M; Butler, Christopher J; Lord, Wayne D

2014-01-01

Climate change is implicated in the alteration of the ranges of species worldwide. Such shifts in species distributions may introduce parasites/pathogens, hosts, and vectors associated with disease to new areas. The parasite Angiostrongylus ( = Parastrongylus) cantonensis is an invasive species that causes eosinophilic meningitis in humans and neurological abnormalities in domestic/wild animals. Although native to southeastern Asia, A. cantonensis has now been reported from more than 30 countries worldwide. Given the health risks, it is important to describe areas with potentially favorable climate for the establishment of A. cantonensis, as well as areas where this pathogen might become established in the future. We used the program Maxent to develop an ecological niche model for A. cantonensis based on 86 localities obtained from published literature. We then modeled areas of potential A. cantonensis distribution as well as areas projected to have suitable climatic conditions under four Representative Concentration Pathways (RCP) scenarios by the 2050s and the 2070s. The best model contained three bioclimatic variables: mean diurnal temperature range, minimum temperature of coldest month and precipitation of warmest quarter. Potentially suitable habitat for A. cantonensis was located worldwide in tropical and subtropical regions. Under all climate change RCP scenarios, the center of the projected distribution shifted away from the equator at a rate of 68-152 km per decade. However, the extent of areas with highly suitable habitat (>50%) declined by 10.66-15.66% by the 2050s and 13.11-16.11% by the 2070s. These results conflict with previous studies, which have generally found that the prevalence of tropical pathogens will increase during the 21st century. Moreover, it is likely that A. cantonensis will continue to expand its current range in the near future due to introductions and host expansion, whereas climate change will reduce the total geographic area of most suitable climatic conditions during the coming decades.

Carbon Source-Dependent Inducible Metabolism of Veratryl Alcohol and Ferulic Acid in Pseudomonas putida CSV86

PubMed Central

Mohan, Karishma

2017-01-01

ABSTRACT Pseudomonas putida CSV86 degrades lignin-derived metabolic intermediates, viz., veratryl alcohol, ferulic acid, vanillin, and vanillic acid, as the sole sources of carbon and energy. Strain CSV86 also degraded lignin sulfonate. Cell respiration, enzyme activity, biotransformation, and high-pressure liquid chromatography (HPLC) analyses suggest that veratryl alcohol and ferulic acid are metabolized to vanillic acid by two distinct carbon source-dependent inducible pathways. Vanillic acid was further metabolized to protocatechuic acid and entered the central carbon pathway via the β-ketoadipate route after ortho ring cleavage. Genes encoding putative enzymes involved in the degradation were found to be present at fer, ver, and van loci. The transcriptional analysis suggests a carbon source-dependent cotranscription of these loci, substantiating the metabolic studies. Biochemical and quantitative real-time (qRT)-PCR studies revealed the presence of two distinct O-demethylases, viz., VerAB and VanAB, involved in the oxidative demethylation of veratric acid and vanillic acid, respectively. This report describes the various steps involved in metabolizing lignin-derived aromatic compounds at the biochemical level and identifies the genes involved in degrading veratric acid and the arrangement of phenylpropanoid metabolic genes as three distinct inducible transcription units/operons. This study provides insight into the bacterial degradation of lignin-derived aromatics and the potential of P. putida CSV86 as a suitable candidate for producing valuable products. IMPORTANCE Pseudomonas putida CSV86 metabolizes lignin and its metabolic intermediates as a carbon source. Strain CSV86 displays a unique property of preferential utilization of aromatics, including for phenylpropanoids over glucose. This report unravels veratryl alcohol metabolism and genes encoding veratric acid O-demethylase, hitherto unknown in pseudomonads, thereby providing new insight into the metabolic pathway and gene pool for lignin degradation in bacteria. The biochemical and genetic characterization of phenylpropanoid metabolism makes it a prospective system for its application in producing valuable products, such as vanillin and vanillic acid, from lignocellulose. This study supports the immense potential of P. putida CSV86 as a suitable candidate for bioremediation and biorefinery. PMID:28188206

Gene expression profiling of canine osteosarcoma reveals genes associated with short and long survival times

PubMed Central

Selvarajah, Gayathri T; Kirpensteijn, Jolle; van Wolferen, Monique E; Rao, Nagesha AS; Fieten, Hille; Mol, Jan A

2009-01-01

Background Gene expression profiling of spontaneous tumors in the dog offers a unique translational opportunity to identify prognostic biomarkers and signaling pathways that are common to both canine and human. Osteosarcoma (OS) accounts for approximately 80% of all malignant bone tumors in the dog. Canine OS are highly comparable with their human counterpart with respect to histology, high metastatic rate and poor long-term survival. This study investigates the prognostic gene profile among thirty-two primary canine OS using canine specific cDNA microarrays representing 20,313 genes to identify genes and cellular signaling pathways associated with survival. This, the first report of its kind in dogs with OS, also demonstrates the advantages of cross-species comparison with human OS. Results The 32 tumors were classified into two prognostic groups based on survival time (ST). They were defined as short survivors (dogs with poor prognosis: surviving fewer than 6 months) and long survivors (dogs with better prognosis: surviving 6 months or longer). Fifty-one transcripts were found to be differentially expressed, with common upregulation of these genes in the short survivors. The overexpressed genes in short survivors are associated with possible roles in proliferation, drug resistance or metastasis. Several deregulated pathways identified in the present study, including Wnt signaling, Integrin signaling and Chemokine/cytokine signaling are comparable to the pathway analysis conducted on human OS gene profiles, emphasizing the value of the dog as an excellent model for humans. Conclusion A molecular-based method for discrimination of outcome for short and long survivors is useful for future prognostic stratification at initial diagnosis, where genes and pathways associated with cell cycle/proliferation, drug resistance and metastasis could be potential targets for diagnosis and therapy. The similarities between human and canine OS makes the dog a suitable pre-clinical model for future 'novel' therapeutic approaches where the current research has provided new insights on prognostic genes, molecular pathways and mechanisms involved in OS pathogenesis and disease progression. PMID:19735553

Microarray analysis of gene expression in the cyclooxygenase knockout mice - a connection to autism spectrum disorder.

PubMed

Rai-Bhogal, Ravneet; Ahmad, Eizaaz; Li, Hongyan; Crawford, Dorota A

2018-03-01

The cellular and molecular events that take place during brain development play an important role in governing function of the mature brain. Lipid-signalling molecules such as prostaglandin E 2 (PGE 2 ) play an important role in healthy brain development. Abnormalities along the COX-PGE 2 signalling pathway due to genetic or environmental causes have been linked to autism spectrum disorder (ASD). This study aims to evaluate the effect of altered COX-PGE 2 signalling on development and function of the prenatal brain using male mice lacking cyclooxygenase-1 and cyclooxygenase-2 (COX-1 -/- and COX-2 -/- ) as potential model systems of ASD. Microarray analysis was used to determine global changes in gene expression during embryonic days 16 (E16) and 19 (E19). Gene Ontology: Biological Process (GO:BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were implemented to identify affected developmental genes and cellular processes. We found that in both knockouts the brain at E16 had nearly twice as many differentially expressed genes, and affected biological pathways containing various ASD-associated genes important in neuronal function. Interestingly, using GeneMANIA and Cytoscape we also show that the ASD-risk genes identified in both COX-1 -/- and COX-2 -/- models belong to protein-interaction networks important for brain development despite of different cellular localization of these enzymes. Lastly, we identified eight genes that belong to the Wnt signalling pathways exclusively in the COX-2 -/- mice at E16. The level of PKA-phosphorylated β-catenin (S552), a major activator of the Wnt pathway, was increased in this model, suggesting crosstalk between the COX-2-PGE 2 and Wnt pathways during early brain development. Overall, these results provide further molecular insight into the contribution of the COX-PGE 2 pathways to ASD and demonstrate that COX-1 -/- and COX-2 -/- animals might be suitable new model systems for studying the disorders. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Degradation pathways of aniline in aqueous solutions during electro-oxidation with BDD electrodes and UV/H2O2 treatment.

PubMed

Benito, Aleix; Penadés, Aida; Lliberia, Josep Lluis; Gonzalez-Olmos, Rafael

2017-01-01

In this work, it has been studied the mineralization of aniline, a toxic substance of low biodegradability typically found in many industrial wastewaters, through electro-oxidation using boron doped diamond (BDD) electrodes and photo-oxidation (UV photolysis and UV/H 2 O 2 treatments). It was observed that in electro-oxidation and UV/H 2 O 2 , it was feasible to reach aniline mineralizations higher than 85%. Two different degradation routes have been observed during the aniline oxidation in these two treatments. The first route was the mineralization pathway, in which aniline was oxidized to CO 2 , water and nitrate. The second route was the polyaniline pathway in which polyanilines of high molecular weight are formed. The intermediate compounds involved in both degradation routes are different depending on the treatment used. In the electro-oxidation, denitrification processes were also observed. From an economical point of view, electro-oxidation of aniline using BDD electrodes is more interesting than UV/H 2 O 2 due it has an 87% lower operational cost. So, electro-oxidation using BDD electrodes seems to be a more suitable technique for the mineralization of wastewater containing aniline than UV or H 2 O 2 based technologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Serum Metabolic Profiling Reveals Altered Metabolic Pathways in Patients with Post-traumatic Cognitive Impairments

PubMed Central

Yi, Lunzhao; Shi, Shuting; Wang, Yang; Huang, Wei; Xia, Zi-an; Xing, Zhihua; Peng, Weijun; Wang, Zhe

2016-01-01

Cognitive impairment, the leading cause of traumatic brain injury (TBI)-related disability, adversely affects the quality of life of TBI patients, and exacts a personal and economic cost that is difficult to quantify. The underlying pathophysiological mechanism is currently unknown, and an effective treatment of the disease has not yet been identified. This study aimed to advance our understanding of the mechanism of disease pathogenesis; thus, metabolomics based on gas chromatography/mass spectrometry (GC-MS), coupled with multivariate and univariate statistical methods were used to identify potential biomarkers and the associated metabolic pathways of post-TBI cognitive impairment. A biomarker panel consisting of nine serum metabolites (serine, pyroglutamic acid, phenylalanine, galactose, palmitic acid, arachidonic acid, linoleic acid, citric acid, and 2,3,4-trihydroxybutyrate) was identified to be able to discriminate between TBI patients with cognitive impairment, TBI patients without cognitive impairment and healthy controls. Furthermore, associations between these metabolite markers and the metabolism of amino acids, lipids and carbohydrates were identified. In conclusion, our study is the first to identify several serum metabolite markers and investigate the altered metabolic pathway that is associated with post-TBI cognitive impairment. These markers appear to be suitable for further investigation of the disease mechanisms of post-TBI cognitive impairment. PMID:26883691

Determination of asymmetric Nα-acetyldimethylarginine in humans: a phase II metabolite of asymmetric dimethylarginine.

PubMed

Martens-Lobenhoffer, Jens; Rodionov, Roman N; Bode-Böger, Stefanie M

2014-05-01

Asymmetric dimethylarginine (ADMA) is produced by protein methylation, a common mechanism of posttranslational protein modification. Elevated levels of ADMA lead to impaired endothelial nitric oxide production and subsequently to a range of cardiovascular and other diseases related to decreased nitric oxide production. Knowledge of the elimination pathways of ADMA and the possibility of influencing them is therefore of major clinical interest. One of these pathways is the N-acetylation and subsequent renal elimination of ADMA in the form of asymmetric Nα-acetyldimethylarginine (Ac-ADMA). In this work, we describe the first method to quantitatively determine Ac-ADMA in human plasma and urine. Ac-ADMA was separated by HPLC on a porous graphitic carbon column and selectively analyzed by tandem mass spectrometry. Ac-ADMA and the internal standard D7-Ac-ADMA were synthesized in-house. Precision and accuracy of the method were better than 5% in plasma and urine quality control samples. First results obtained with this method in samples of healthy volunteers showed plasma levels of 0.643±0.454 nmol/L and urine levels of 152.7±76.7 nmol/L or 13.0±8.9 nmol/mmol creatinine. The method is a suitable tool for investigating this currently mostly neglected ADMA elimination pathway. Copyright © 2014 Elsevier Inc. All rights reserved.

A management-oriented framework for selecting metrics used to assess habitat- and path-specific quality in spatially structured populations

USGS Publications Warehouse

Nicol, Sam; Wiederholt, Ruscena; Diffendorfer, James E.; Mattsson, Brady; Thogmartin, Wayne E.; Semmens, Darius J.; Laura Lopez-Hoffman,; Norris, Ryan

2016-01-01

Mobile species with complex spatial dynamics can be difficult to manage because their population distributions vary across space and time, and because the consequences of managing particular habitats are uncertain when evaluated at the level of the entire population. Metrics to assess the importance of habitats and pathways connecting habitats in a network are necessary to guide a variety of management decisions. Given the many metrics developed for spatially structured models, it can be challenging to select the most appropriate one for a particular decision. To guide the management of spatially structured populations, we define three classes of metrics describing habitat and pathway quality based on their data requirements (graph-based, occupancy-based, and demographic-based metrics) and synopsize the ecological literature relating to these classes. Applying the first steps of a formal decision-making approach (problem framing, objectives, and management actions), we assess the utility of metrics for particular types of management decisions. Our framework can help managers with problem framing, choosing metrics of habitat and pathway quality, and to elucidate the data needs for a particular metric. Our goal is to help managers to narrow the range of suitable metrics for a management project, and aid in decision-making to make the best use of limited resources.

Gluconate as suitable potential reduction supplier in Corynebacterium glutamicum: cloning and expression of gntP and gntK in Escherichia coli.

PubMed

Porco, Antonietta; Gamero, Elida E; Mylonás, Elena; Istúriz, Tomás

2008-01-01

Corynebacterium glutamicum is widely used in the industrial production of amino acids. We have found that this bacterium grows exponentially on a mineral medium supplemented with gluconate. Gluconate permease and Gluconokinase are expressed in an inducible form and, 6-phosphogluconate dehydrogenase, although constitutively expressed, shows a 3-fold higher specific level in gluconate grown cells than those grown in fructose under similar conditions. Interestingly, these activities are lower than those detected in the strain Escherichia coli M1-8, cultivated under similar conditions. Additionally, here we also confirmed that this bacterium lacks 6-phosphogluconate dehydratase activity. Thus, gluconate must be metabolized through the pentose phosphate pathway. Genes encoding gluconate transport and its phosphorylation were cloned from C. glutamicum, and expressed in suitable E. coli mutants. Sequence analysis revealed that the amino acid sequences obtained from these genes, denoted as gntP and gntK, were similar to those found in other bacteria. Analysis of both genes by RT-PCR suggested constitutive expression, in disagreement with the inducible character of their corresponding activities. The results suggest that gluconate might be a suitable source of reduction potential for improving the efficiency in cultures engaged in amino acids production. This is the first time that gluconate specific enzymatic activities are reported in C. glutamicum.

Suitable simple and fast methods for selective isolation of phospholipids as a tool for their analysis.

PubMed

Pimentel, Lígia; Fontes, Ana Luiza; Salsinha, Sofia; Machado, Manuela; Correia, Inês; Gomes, Ana Maria; Pintado, Manuela; Rodríguez-Alcalá, Luís Miguel

2018-03-08

Lipids are gaining relevance over the last 20 years, as our knowledge about their role has changed from merely energy/structural molecules to compounds also involved in several biological processes. This led to the creation in 2003 of a new emerging research field: lipidomics. In particular the phospholipids have pharmacological/food applications, participate in cell signalling/homeostatic pathways while their analysis faces some challenges. Their fractionation/purification is, in fact, especially difficult, as they are amphiphilic compounds. Moreover, it usually involves SPE or TLC procedures requiring specific materials hampering their suitableness for routine analysis. Finally, they can interfere with the ionization of other molecules during mass spectrometry analysis. Thus, simple high-throughput reliable methods to selectively isolate these compounds based on the difference between chemical characteristics of lipids would represent valuable tools for their study besides that of other compounds. The current review work aims to describe the state-of-the-art related to the extraction of phospholipids using liquid-liquid methods for their targeted isolation. The technological and biological importance of these compounds and ion suppression phenomena are also reviewed. Methods by precipitation with acetone or isolation using methanol seem to be suitable for selective isolation of phospholipids in both biological and food samples. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ganglioneuritis causing high mortalities in farmed Australian abalone (Haliotis laevigata and Haliotis rubra).

PubMed

Hooper, C; Hardy-Smith, P; Handlinger, J

2007-05-01

To investigate an outbreak of sudden severe mortality in farmed abalone from coastal Victoria. The outbreaks occurred almost simultaneously in three farms following abalone movements from the wild and between farms. The initial on farm investigation identified a number of features that when considered together were highly suggestive of an infectious aetiology. In many cases, dead abalone had no significant gross lesions. Others had swollen mouths and some had prolapse and eversion of the radula. Histologically, the lesions centred on the nerves innervating the labial apparatus, primarily the cerebral and buccal ganglia, cerebral commissure and peripheral nerve branches arising from these. Nervous tissue necrosis and haemocyte infiltration were the dominant lesions seen microscopically in affected nerves. A recent outbreak of mortality in Australian abalone was associated with neurotropic lesions, which have not previously been described in this country. The on farm and between farm pattern of spread of the outbreak, a history of abalone movements linking farms, clinical observation of moribund and dead abalone were all highly suggestive of a virulent infectious agent.

Nervous-Tissue-Specific Elimination of Microtubule-Actin Crosslinking Factor 1a Results in Multiple Developmental Defects in the Mouse Brain

PubMed Central

Goryunov, Dmitry; He, Cui-Zhen; Lin, Chyuan-Sheng; Leung, Conrad L.; Liem, Ronald K. H.

2010-01-01

The microtubule-actin crosslinking factor 1 (MACF1) is a ubiquitous cytoskeletal linker protein with multiple spliced isoforms expressed in different tissues. The MACF1a isoform contains microtubule and actin binding regions and is expressed at high levels in the nervous system. Macf1−/− mice are early embryonic lethal and hence the role of MACF1 in the nervous system could not be determined. We have specifically knocked out MACF1a in the developing mouse nervous system using Cre/loxP technology. Mutant mice died within 24–36 hrs after birth of apparent respiratory distress. Their brains displayed a disorganized cerebral cortex with a mixed layer structure, heterotopia in the pyramidal layer of the hippocampus, disorganized thalamocortical and corticofugal fibers, and aplastic anterior and hippocampal commissures. Embryonic neurons showed a defect in traversing the cortical plate. Our data suggest a critical role for MACF1 in neuronal migration that is dependent on its ability to interact with both microfilaments and microtubules. PMID:20170731

Nervous-tissue-specific elimination of microtubule-actin crosslinking factor 1a results in multiple developmental defects in the mouse brain.

PubMed

Goryunov, Dmitry; He, Cui-Zhen; Lin, Chyuan-Sheng; Leung, Conrad L; Liem, Ronald K H

2010-05-01

The microtubule-actin crosslinking factor 1 (MACF1) is a ubiquitous cytoskeletal linker protein with multiple spliced isoforms expressed in different tissues. The MACF1a isoform contains microtubule and actin-binding regions and is expressed at high levels in the nervous system. Macf1-/- mice are early embryonic lethal and hence the role of MACF1 in the nervous system could not be determined. We have specifically knocked out MACF1a in the developing mouse nervous system using Cre/loxP technology. Mutant mice died within 24-36h after birth of apparent respiratory distress. Their brains displayed a disorganized cerebral cortex with a mixed layer structure, heterotopia in the pyramidal layer of the hippocampus, disorganized thalamocortical and corticofugal fibers, and aplastic anterior and hippocampal commissures. Embryonic neurons showed a defect in traversing the cortical plate. Our data suggest a critical role for MACF1 in neuronal migration that is dependent on its ability to interact with both microfilaments and microtubules. Copyright 2010 Elsevier Inc. All rights reserved.

A case of vesicular cutaneous lupus erythematosus in a Border collie successfully treated with topical tacrolimus and nicotinamide-tetracycline.

PubMed

Lehner, Georg M; Linek, Monika

2013-12-01

Canine vesicular cutaneous lupus erythematosus (VCLE) is an autoimmune skin disease of the Shetland sheepdog and rough collie, which manifests as an erosive dermatitis of sparsely haired skin of the ventrum and concave pinnae. Reported treatment consists of immunosuppression with glucocorticoids alone or in combination with azathioprine, but successful treatment is unpredictable. To report on the treatment of VCLE in a Border collie dog with topical 0.1% tacrolimus and nicotinamide in combination with tetracycline. An 8-year-old male neutered Border collie was presented with multiple coalescing erosions on the ventral abdomen, groin and axillae and ulceration on the oral commissures. Clinical presentation, routine diagnostics, histology and immunohistochemistry were consistent with VCLE. Remission was achieved with topical 0.1% tacrolimus and combination therapy of nicotinamide and tetracycline. This dog responded well to treatment with topical 0.1% tacrolimus, nicotinamide-tetracycline and sun avoidance. Complete remission was achieved after 2.5 months, and the dog was lesion free during a 1 year follow-up period. © 2013 ESVD and ACVD.

On describing human white matter anatomy: the white matter query language.

PubMed

Wassermann, Demian; Makris, Nikos; Rathi, Yogesh; Shenton, Martha; Kikinis, Ron; Kubicki, Marek; Westin, Carl-Fredrik

2013-01-01

The main contribution of this work is the careful syntactical definition of major white matter tracts in the human brain based on a neuroanatomist's expert knowledge. We present a technique to formally describe white matter tracts and to automatically extract them from diffusion MRI data. The framework is based on a novel query language with a near-to-English textual syntax. This query language allows us to construct a dictionary of anatomical definitions describing white matter tracts. The definitions include adjacent gray and white matter regions, and rules for spatial relations. This enables automated coherent labeling of white matter anatomy across subjects. We use our method to encode anatomical knowledge in human white matter describing 10 association and 8 projection tracts per hemisphere and 7 commissural tracts. The technique is shown to be comparable in accuracy to manual labeling. We present results applying this framework to create a white matter atlas from 77 healthy subjects, and we use this atlas in a proof-of-concept study to detect tract changes specific to schizophrenia.

Comparative Study of the Major White Matter Tracts Anatomy in Equine, Feline and Canine Brains by Use of the Fibre Dissection Technique.

PubMed

Pascalau, R; Aldea, C C; Padurean, V A; Szabo, B

2016-10-01

The spatial anatomy of the white matter tracts is a subject of growing interest not only for researchers but also for clinicians. Imagistic methods have some limitations so that they should be confronted with dissection studies. The aim of this paper was to provide a three-dimensional view of the major white matter tracts in equine, feline and canine brains by use of the fibre dissection technique. Twenty cerebral hemispheres (six equine, four feline and 10 canine brains) were prepared according to the Klingler method. Stepwise mediolateral and lateromedial blunt dissections were performed using wooden sticks and spatulas. The lateromedial dissection was followed by the opening of the lateral ventricle. The use of the same multi-stage procedures resulted in a comparable exposure of the major association, projection and commissural fibres and their spatial relation with the lateral ventricle. To conclude, the proposed techniques are reproducible in equine, feline and canine brains and they can be successfully used for teaching, training or research in the field of neurobiology. © 2015 Blackwell Verlag GmbH.

Further studies on the cortical connections of the Tegu lizard.

PubMed

Lohman, A H; Van Woerden-Verkley, I

1976-02-13

The efferent fiber connections of the caudal half of the cerebral cortex, the lateral cortex and the pallial thickening were studied using the Nauta-Gygax and Fink-Heimer techniques. The following observations were made, (1) In the caudal half of the hemisphere corticoseptal and corticohypothalamic fibers originate from the small-celled part of the mediodorsal cortex and the thickened caudal part of the dorsal cortex in its whole mediolateral extent. (2) The dorsal cortex in the middle of the hemisphere projects by way of both the pre- and postcommissural fornices. Its rostral pole distributes its fibers solely to the postcommissural fornix, whereas its caudal part projects via the precommissural fornix. (3) The posterior pallial commissure carries fibers that arise caudally in the small-celled part of the mediodorsal cortex and terminate in the contralateral ventral cortex. (4) Projections to the dorsal striatum originate from the lateral cortex, the dorsal cortex and the superficial portion of the pallial thickening. In addition, the latter two zones project to the nucleus accumbens. (5) The deep portion of the pallial thickening projects to the ventral striatum.

The L1-CAM, Neuroglian, functions in glial cells for Drosophila antennal lobe development.

PubMed

Chen, Weitao; Hing, Huey

2008-07-01

Although considerable progress has been made in understanding the roles of olfactory receptor neurons (ORNs) and projection neurons (PNs) in Drosophila antennal lobe (AL) development, the roles of glia have remained largely mysterious. Here, we show that during Drosophila metamorphosis, a population of midline glial cells in the brain undergoes extensive cellular remodeling and is closely associated with the collateral branches of ORN axons. These glial cells are required for ORN axons to project across the midline and establish the contralateral wiring in the ALs. We find that Neuroglian (Nrg), the Drosophila homolog of the vertebrate cell adhesion molecule, L1, is expressed and functions in the midline glial cells to regulate their proper development. Loss of Nrg causes the disruption in glial morphology and the agenesis of the antennal commissural tract. Our genetic analysis further demonstrates that the functions of Nrg in the midline glia require its ankyrin-binding motif. We propose that Nrg is an important regulator of glial morphogenesis and axon guidance in AL development. (Copyright) 2008 Wiley Periodicals, Inc.

Objective assessment of isotretinoin-associated cheilitis: Isotretinoin Cheilitis Grading Scale.

PubMed

Ornelas, Jennifer; Rosamilia, Lorraine; Larsen, Larissa; Foolad, Negar; Wang, Quinlu; Li, Chin-Shang; Sivamani, Raja K

2016-01-01

Isotretinoin remains an effective treatment for severe acne. Despite its effectiveness, it includes many side effects, of which cheilitis is the most common. To develop an objective grading scale for assessment of isotretinoin-associated cheilitis. Cross-sectional clinical grading study. UC Davis Dermatology clinic. Subjects were older than 18 years old and actively treated with oral isotretinoin. Oral Isotretinoin. We developed an Isotretinoin Cheilitis Grading Scale (ICGS) incorporating the following four characteristics: erythema, scale/crust, fissures and inflammation of the commissures. Three board-certified dermatologists independently graded photographs of the subjects. The Kendall's coefficient of concordance (KCC) for the ICGS was 0.88 (p < 0.0001). The Kendall's coefficient was ≥0.72 (p < 0.0001) for each of the four characteristics included in the grading scale. An image-based measurement for lip roughness statistically significantly correlated with the lip scale/crusting assessment (r = 0.52, p < 0.05). The ICGS is reproducible and relatively simple to use. It can be incorporated as an objective tool to aid in the assessment of isotretinoin associated cheilitis.

Comparative study on the microbiological features of angular cheilitis in HIV seropositive and HIV seronegative patients from South India

PubMed Central

Krishnan, P Anitha; Kannan, Ranganathan

2013-01-01

Objective: This study was designed to compare the microbiological features of angular cheilitis (AC) in human immunodeficiency virus (HIV) seropositive and HIV seronegative individuals, in a group of south Indians. Materials and Methods: Swabs from oral commissures of 46 patients were obtained and inoculated on to Sabouraud's dextrose agar (SDA) supplemented with chloramphenicol, blood agar (BA) and MacConkey's agar (MCA) plates and cultured. α-hemolytic Streptococci, Staphylococcus albus, Staphylococcus aureus, Candida species, Klebsiella species and Pseudomonas species were cultured. Candidal colonies were further speciated by the conventional biotyping technique. Results: In AC of HIV seropositive patients Candida albicans and Staphylococcus aureus were more prevalent than that in HIV seronegative patients. Incidentally in patients with CD4 cell count less than 200 there was an increase in the incidence of Candidal and Staphylococcus aureus colonization when compared to patients with CD4 cell count higher than 200. Conclusion: The present study suggests a definite difference in the microbial flora of AC in HIV seropositive patients than that of HIV seronegative population. PMID:24574650

Effect of postoperative brachytherapy and external beam radiotherapy on functional outcomes of immediate facial nerve repair after radical parotidectomy.

PubMed

Hontanilla, Bernardo; Qiu, Shan-Shan; Marré, Diego

2014-01-01

There is much controversy regarding the effect of radiotherapy on facial nerve regeneration. However, the effect of brachytherapy has not been studied. Fifty-three patients underwent total parotidectomy of which 13 were radical with immediate facial nerve repair with sural nerve grafts. Six patients (group 1) did not receive adjuvant treatment whereas 7 patients (group 2) received postoperative brachytherapy plus radiotherapy. Functional outcomes were compared using Facial Clima. Mean percentage of blink recovery was 92.6 ± 4.2 for group 1 and 90.7 ± 5.2 for group 2 (p = .37). Mean percentage of commissural excursion restoration was 78.1 ± 3.5 for group 1 and 74.9 ± 5.9 for group 2 (p = .17). Mean time from surgery to first movement was 5.7 ± 0.9 months for group 1 and 6.3 ± 0.5 months for group 2 (p = .15). Brachytherapy plus radiotherapy does not affect the functional outcomes of immediate facial nerve repair with nerve grafts. Copyright © 2013 Wiley Periodicals, Inc.

Potential Involvement of Draxin in the Axonal Projection of Cranial Nerves, Especially Cranial Nerve X, in the Chick Hindbrain

PubMed Central

Zhang, Sanbing; Cui, Huixian; Wang, Lei; Kang, Lin; Huang, Guannan; Du, Juan; Li, Sha; Tanaka, Hideaki; Su, Yuhong

2016-01-01

The appropriate projection of axons within the nervous system is a crucial component of the establishment of neural circuitry. Draxin is a repulsive axon guidance protein. Draxin has important functions in the guidance of three commissures in the central nervous system and in the migration of neural crest cells and dI3 interneurons in the chick spinal cord. Here, we report that the distribution of the draxin protein and the location of 23C10-positive areas have a strong temporal and spatial correlation. The overexpression of draxin, especially transmembrane draxin, caused 23C10-positive axon bundles to misproject in the dorsal hindbrain. In addition, the overexpression of transmembrane draxin caused abnormal formation of the ganglion crest of the IX and X cranial nerves, misprojection of some anti-human natural killer-1 (HNK-1)-stained structures in the dorsal roof of the hindbrain, and a simultaneous reduction in the efferent nerves of some motoneuron axons inside the hindbrain. Our data reveal that draxin might be involved in the fascicular projection of cranial nerves in the hindbrain. PMID:27199282

Environmental Suitability of Vibrio Infections in a Warming Climate: An Early Warning System.

PubMed

Semenza, Jan C; Trinanes, Joaquin; Lohr, Wolfgang; Sudre, Bertrand; Löfdahl, Margareta; Martinez-Urtaza, Jaime; Nichols, Gordon L; Rocklöv, Joacim

2017-10-10

Some Vibrio spp. are pathogenic and ubiquitous in marine waters with low to moderate salinity and thrive with elevated sea surface temperature (SST). Our objective was to monitor and project the suitability of marine conditions for Vibrio infections under climate change scenarios. The European Centre for Disease Prevention and Control (ECDC) developed a platform (the ECDC Vibrio Map Viewer) to monitor the environmental suitability of coastal waters for Vibrio spp. using remotely sensed SST and salinity. A case-crossover study of Swedish cases was conducted to ascertain the relationship between SST and Vibrio infection through a conditional logistic regression. Climate change projections for Vibrio infections were developed for Representative Concentration Pathway (RCP) 4.5 and RCP 8.5. The ECDC Vibrio Map Viewer detected environmentally suitable areas for Vibrio spp. in the Baltic Sea in July 2014 that were accompanied by a spike in cases and one death in Sweden. The estimated exposure-response relationship for Vibrio infections at a threshold of 16°C revealed a relative risk (RR)=1.14 (95% CI: 1.02, 1.27; p=0.024) for a lag of 2 wk; the estimated risk increased successively beyond this SST threshold. Climate change projections for SST under the RCP 4.5 and RCP 8.5 scenarios indicate a marked upward trend during the summer months and an increase in the relative risk of these infections in the coming decades. This platform can serve as an early warning system as the risk of further Vibrio infections increases in the 21st century due to climate change. https://doi.org/10.1289/EHP2198.

Environmental Suitability of Vibrio Infections in a Warming Climate: An Early Warning System

PubMed Central

Trinanes, Joaquin; Lohr, Wolfgang; Sudre, Bertrand; Löfdahl, Margareta; Martinez-Urtaza, Jaime; Nichols, Gordon L.; Rocklöv, Joacim

2017-01-01

Background: Some Vibrio spp. are pathogenic and ubiquitous in marine waters with low to moderate salinity and thrive with elevated sea surface temperature (SST). Objectives: Our objective was to monitor and project the suitability of marine conditions for Vibrio infections under climate change scenarios. Methods: The European Centre for Disease Prevention and Control (ECDC) developed a platform (the ECDC Vibrio Map Viewer) to monitor the environmental suitability of coastal waters for Vibrio spp. using remotely sensed SST and salinity. A case-crossover study of Swedish cases was conducted to ascertain the relationship between SST and Vibrio infection through a conditional logistic regression. Climate change projections for Vibrio infections were developed for Representative Concentration Pathway (RCP) 4.5 and RCP 8.5. Results: The ECDC Vibrio Map Viewer detected environmentally suitable areas for Vibrio spp. in the Baltic Sea in July 2014 that were accompanied by a spike in cases and one death in Sweden. The estimated exposure–response relationship for Vibrio infections at a threshold of 16°C revealed a relative risk (RR)=1.14 (95% CI: 1.02, 1.27; p=0.024) for a lag of 2 wk; the estimated risk increased successively beyond this SST threshold. Climate change projections for SST under the RCP 4.5 and RCP 8.5 scenarios indicate a marked upward trend during the summer months and an increase in the relative risk of these infections in the coming decades. Conclusions: This platform can serve as an early warning system as the risk of further Vibrio infections increases in the 21st century due to climate change. https://doi.org/10.1289/EHP2198 PMID:29017986

Carbon-climate feedbacks accelerate ocean acidification

NASA Astrophysics Data System (ADS)

Matear, Richard J.; Lenton, Andrew

2018-03-01

Carbon-climate feedbacks have the potential to significantly impact the future climate by altering atmospheric CO2 concentrations (Zaehle et al. 2010). By modifying the future atmospheric CO2 concentrations, the carbon-climate feedbacks will also influence the future ocean acidification trajectory. Here, we use the CO2 emissions scenarios from four representative concentration pathways (RCPs) with an Earth system model to project the future trajectories of ocean acidification with the inclusion of carbon-climate feedbacks. We show that simulated carbon-climate feedbacks can significantly impact the onset of undersaturated aragonite conditions in the Southern and Arctic oceans, the suitable habitat for tropical coral and the deepwater saturation states. Under the high-emissions scenarios (RCP8.5 and RCP6), the carbon-climate feedbacks advance the onset of surface water under saturation and the decline in suitable coral reef habitat by a decade or more. The impacts of the carbon-climate feedbacks are most significant for the medium- (RCP4.5) and low-emissions (RCP2.6) scenarios. For the RCP4.5 scenario, by 2100 the carbon-climate feedbacks nearly double the area of surface water undersaturated with respect to aragonite and reduce by 50 % the surface water suitable for coral reefs. For the RCP2.6 scenario, by 2100 the carbon-climate feedbacks reduce the area suitable for coral reefs by 40 % and increase the area of undersaturated surface water by 20 %. The sensitivity of ocean acidification to the carbon-climate feedbacks in the low to medium emission scenarios is important because recent CO2 emission reduction commitments are trying to transition emissions to such a scenario. Our study highlights the need to better characterise the carbon-climate feedbacks and ensure we do not underestimate the projected ocean acidification.

All fats are not equal: Considerations when using fatty acid biomarkers in compound-specific stable isotope soil and sediment tracing

NASA Astrophysics Data System (ADS)

Reiffarth, Dominic; Petticrew, Ellen; Owens, Philip; Lobb, David

2013-04-01

The development of cost-effective, convenient and reliable methods for tracing sediment movement will help establish water security. The use of compound-specific stable isotopes (CSSIs) has seen limited, small-scale applications, often in watersheds exhibiting exotic and highly diverse vegetation types. The CSSI tracing technique relies on the detection and transport of naturally occurring organics of plant origin (biomarkers); the biomarkers of interest are produced by flora, deposited on the soil and potentially mobilized along with soil particles. In part, the uniqueness of a biomarker is dependent on its biological pathway. As a plant fixes CO2-its primary source of carbon for building larger organic molecules-discrimination against the heavier 13C isotope leads to an enrichment of 12C. The more complex the biological pathway the biomarker has been subjected to, the more discrimination and unique isotopic signature the biomarker exhibits. Successfully implementing CSSI tracing requires recognizing: (i) factors contributing to the natural variability of the isotopic signature (ii) the suitability of a biomarker and (iii) factors affecting sensitivity during analysis. Considering the relatively low input of suitable organic biomarkers into the soil and degree of signal dispersion, care must be taken to isolate and correctly identify biomarkers, particularly where vegetation types show low variability and where long-range transport occurs. Research is currently being conducted in the Horsefly River (British Columbia, Canada) and South Tobacco Creek (Manitoba, Canada) watersheds; the research seeks to address some of these concerns, particularly in a temperate climate where exotic vegetation types are not common and variability is expected to be low.

Characterization of Brachypodium distachyon as a nonhost model against switchgrass rust pathogen Puccinia emaculata.

PubMed

Gill, Upinder S; Uppalapati, Srinivasa R; Nakashima, Jin; Mysore, Kirankumar S

2015-05-08

Switchgrass rust, caused by Puccinia emaculata, is an important disease of switchgrass, a potential biofuel crop in the United States. In severe cases, switchgrass rust has the potential to significantly affect biomass yield. In an effort to identify novel sources of resistance against switchgrass rust, we explored nonhost resistance against P. emaculata by characterizing its interactions with six monocot nonhost plant species. We also studied the genetic variations for resistance among Brachypodium inbred accessions and the involvement of various defense pathways in nonhost resistance of Brachypodium. We characterized P. emaculata interactions with six monocot nonhost species and identified Brachypodium distachyon (Bd21) as a suitable nonhost model to study switchgrass rust. Interestingly, screening of Brachypodium accessions identified natural variations in resistance to switchgrass rust. Brachypodium inbred accessions Bd3-1 and Bd30-1 were identified as most and least resistant to switchgrass rust, respectively, when compared to tested accessions. Transcript profiling of defense-related genes indicated that the genes which were induced in Bd21after P. emaculata inoculation also had higher basal transcript abundance in Bd3-1 when compared to Bd30-1 and Bd21 indicating their potential involvement in nonhost resistance against switchgrass rust. In the present study, we identified Brachypodium as a suitable nonhost model to study switchgrass rust which exhibit type I nonhost resistance. Variations in resistance response were also observed among tested Brachypodium accessions. Brachypodium nonhost resistance against P. emaculata may involve various defense pathways as indicated by transcript profiling of defense related genes. Overall, this study provides a new avenue to utilize novel sources of nonhost resistance in Brachypodium against switchgrass rust.

Production of functional human insulin-like growth factor binding proteins (IGFBPs) using recombinant expression in HEK293 cells.

PubMed

Wanscher, Anne Sofie Molsted; Williamson, Michael; Ebersole, Tasja Wainani; Streicher, Werner; Wikström, Mats; Cazzamali, Giuseppe

2015-04-01

Insulin-like growth factor binding proteins (IGFBPs) display many functions in humans including regulation of the insulin-like growth factor (IGF) signaling pathway. The various roles of human IGFBPs make them attractive protein candidates in drug discovery. Structural and functional knowledge on human proteins with therapeutic relevance is needed to design and process the next generation of protein therapeutics. In order to conduct structural and functional investigations large quantities of recombinant proteins are needed. However, finding a suitable recombinant production system for proteins such as full-length human IGFBPs, still remains a challenge. Here we present a mammalian HEK293 expression method suitable for over-expression of secretory full-length human IGFBP-1 to -7. Protein purification of full-length human IGFBP-1, -2, -3 and -5 was conducted using a two-step chromatography procedure and the final protein yields were between 1 and 12mg protein per liter culture media. The recombinant IGFBPs contained PTMs and exhibited high-affinity interactions with their natural ligands IGF-1 and IGF-2. Copyright © 2014 Elsevier Inc. All rights reserved.

Involvement of plasma membrane peroxidases and oxylipin pathway in the recovery from phytoplasma disease in apple (Malus domestica).

PubMed

Patui, Sonia; Bertolini, Alberto; Clincon, Luisa; Ermacora, Paolo; Braidot, Enrico; Vianello, Angelo; Zancani, Marco

2013-06-01

Apple trees (Malus domestica Borkh.) may be affected by apple proliferation (AP), caused by 'Candidatus Phytoplasma mali'. Some plants can spontaneously recover from the disease, which implies the disappearance of symptoms through a phenomenon known as recovery. In this article it is shown that NAD(P)H peroxidases of leaf plasma membrane-enriched fractions exhibited a higher activity in samples from both AP-diseased and recovered plants. In addition, an increase in endogenous SA was characteristic of the symptomatic plants, since its content increased in samples obtained from diseased apple trees. In agreement, phenylalanine ammonia lyase (PAL) activity, a key enzyme of the phenylpropanoid pathway, was increased too. Jasmonic acid (JA) increased only during recovery, in a phase subsequent to the pathological state, and in concomitance to a decline of salicylic acid (SA). Oxylipin pathway, responsible for JA synthesis, was not induced during the development of AP-disease, but it appeared to be stimulated when the recovery occurred. Accordingly, lipoxygenase (LOX) activity, detected in plasma membrane-enriched fractions, showed an increase in apple leaves obtained from recovered plants. This enhancement was paralleled by an increase of hydroperoxide lyase (HPL) activity, detected in leaf microsomes, albeit the latter enzyme was activated in either the disease or recovery conditions. Hence, a reciprocal antagonism between SA- and JA-pathways could be suggested as an effective mechanism by which apple plants react to phytoplasma invasions, thereby providing a suitable defense response leading to the establishment of the recovery phenomenon. Copyright © Physiologia Plantarum 2012.

Interleukins and their signaling pathways in the Reactome biological pathway database.

PubMed

Jupe, Steve; Ray, Keith; Roca, Corina Duenas; Varusai, Thawfeek; Shamovsky, Veronica; Stein, Lincoln; D'Eustachio, Peter; Hermjakob, Henning

2018-04-01

There is a wealth of biological pathway information available in the scientific literature, but it is spread across many thousands of publications. Alongside publications that contain definitive experimental discoveries are many others that have been dismissed as spurious, found to be irreproducible, or are contradicted by later results and consequently now considered controversial. Many descriptions and images of pathways are incomplete stylized representations that assume the reader is an expert and familiar with the established details of the process, which are consequently not fully explained. Pathway representations in publications frequently do not represent a complete, detailed, and unambiguous description of the molecules involved; their precise posttranslational state; or a full account of the molecular events they undergo while participating in a process. Although this might be sufficient to be interpreted by an expert reader, the lack of detail makes such pathways less useful and difficult to understand for anyone unfamiliar with the area and of limited use as the basis for computational models. Reactome was established as a freely accessible knowledge base of human biological pathways. It is manually populated with interconnected molecular events that fully detail the molecular participants linked to published experimental data and background material by using a formal and open data structure that facilitates computational reuse. These data are accessible on a Web site in the form of pathway diagrams that have descriptive summaries and annotations and as downloadable data sets in several formats that can be reused with other computational tools. The entire database and all supporting software can be downloaded and reused under a Creative Commons license. Pathways are authored by expert biologists who work with Reactome curators and editorial staff to represent the consensus in the field. Pathways are represented as interactive diagrams that include as much molecular detail as possible and are linked to literature citations that contain supporting experimental details. All newly created events undergo a peer-review process before they are added to the database and made available on the associated Web site. New content is added quarterly. The 63rd release of Reactome in December 2017 contains 10,996 human proteins participating in 11,426 events in 2,179 pathways. In addition, analytic tools allow data set submission for the identification and visualization of pathway enrichment and representation of expression profiles as an overlay on Reactome pathways. Protein-protein and compound-protein interactions from several sources, including custom user data sets, can be added to extend pathways. Pathway diagrams and analytic result displays can be downloaded as editable images, human-readable reports, and files in several standard formats that are suitable for computational reuse. Reactome content is available programmatically through a REpresentational State Transfer (REST)-based content service and as a Neo4J graph database. Signaling pathways for IL-1 to IL-38 are hierarchically classified within the pathway "signaling by interleukins." The classification used is largely derived from Akdis et al. The addition to Reactome of a complete set of the known human interleukins, their receptors, and established signaling pathways linked to annotations of relevant aspects of immune function provides a significant computationally accessible resource of information about this important family. This information can be extended easily as new discoveries become accepted as the consensus in the field. A key aim for the future is to increase coverage of gene expression changes induced by interleukin signaling. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Ligand-directed profiling of organelles with internalizing phage libraries

PubMed Central

Dobroff, Andrey S.; Rangel, Roberto; Guzman-Roja, Liliana; Salmeron, Carolina C.; Gelovani, Juri G.; Sidman, Richard L.; Bologa, Cristian G.; Oprea, Tudor I.; Brinker, C. Jeffrey; Pasqualini, Renata; Arap, Wadih

2015-01-01

Phage display is a resourceful tool to, in an unbiased manner, discover and characterize functional protein-protein interactions, to create vaccines, and to engineer peptides, antibodies, and other proteins as targeted diagnostic and/or therapeutic agents. Recently, our group has developed a new class of internalizing phage (iPhage) for ligand-directed targeting of organelles and/or to identify molecular pathways within live cells. This unique technology is suitable for applications ranging from fundamental cell biology to drug development. Here we describe the method for generating and screening the iPhage display system, and explain how to select and validate candidate internalizing homing peptide. PMID:25640897

Walking over 4 Gya: Chemical Evolution from Photochemistry to Mineral and Organic Chemistries Leading to an RNA World

NASA Astrophysics Data System (ADS)

Kawamura, Kunio; Maurel, Marie-Christine

2017-09-01

Here we overview the chemical evolution of RNA molecules from inorganic material through mineral-mediated RNA formation compatible with the plausible early Earth environments. Pathways from the gas-phase reaction to the formation of nucleotides, activation and oligomerization of nucleotides, seem to be compatible with specific environments. However, how these steps interacted is not clear since the chemical conditions are frequently different and can be incompatible between them; thus the products would have migrated from one place to another, suitable for further chemical evolution. In this review, we summarize certain points to scrutinize the RNA World hypothesis.

Synthetic biology for microbial production of lipid-based biofuels.

PubMed

d'Espaux, Leo; Mendez-Perez, Daniel; Li, Rachel; Keasling, Jay D

2015-12-01

The risks of maintaining current CO2 emission trends have led to interest in producing biofuels using engineered microbes. Microbial biofuels reduce emissions because CO2 produced by fuel combustion is offset by CO2 captured by growing biomass, which is later used as feedstock for biofuel fermentation. Hydrocarbons found in petroleum fuels share striking similarity with biological lipids. Here we review synthetic metabolic pathways based on fatty acid and isoprenoid metabolism to produce alkanes and other molecules suitable as biofuels. We further discuss engineering strategies to optimize engineered biosynthetic routes, as well as the potential of synthetic biology for sustainable manufacturing. Published by Elsevier Ltd.

Preparation of water-soluble magnetic nanocrystals using aryl diazonium salt chemistry.

PubMed

Griffete, Nébéwia; Herbst, Frédéric; Pinson, Jean; Ammar, Souad; Mangeney, Claire

2011-02-16

A novel and facile methodology for the in situ surface functionalization of Fe(3)O(4) nanoparticles is proposed, based on the use of aryl diazonium salts chemistry. The grafting reaction involves the formation of diazoates in a basic medium. These species are unstable and dediazonize along a homolytic pathway to give aryl radicals which further react with the Fe(3)O(4) NPs during their formation and stop their growth. Advantages of the present approach rely not only on the simplicity, rapidity, and efficiency of the procedure but also on the formation of strong Fe(3)O(4)-aryl surface bonds, highly suitable for further applications.

Oxidation of aliphatic, branched chain, and aromatic hydrocarbons by Nocardia cyriacigeorgica isolated from oil-polluted sand samples collected in the Saudi Arabian Desert.

PubMed

Le, Thi Nhi-Cong; Mikolasch, Annett; Awe, Susanne; Sheikhany, Halah; Klenk, Hans-Peter; Schauer, Frieder

2010-06-01

A soil bacterium isolated from oil-polluted sand samples collected in the Saudi Arabian Desert has been determined as Nocardia cyriacigeorgica, which has a high capacity of degrading and utilizing a broad range of hydrocarbons. The metabolic pathways of three classes of hydrocarbons were elucidated by identifying metabolites in cell-free extracts analyzed by GC/MS and HPLC/UV-Vis in comparison with standard compounds. During tetradecane oxidation, tetradecanol; tetradecanoic acid; dodecanoic acid; decanoic acid could be found as metabolites, indicating a monoterminal degradation pathway of n -alkanes. The oxidation of pristane resulted in the presence of pristanoic acid; 2-methylglutaric acid; 4,8-dimethylnonanoic acid; and 2,6-dimethylheptanoic acid, which give rise to a possible mono- and di-terminal oxidation. In case of sec -octylbenzene, eight metabolites were detected including 5-phenylhexanoic acid; 3-phenylbutyric acid; 2-phenylpropionic acid; beta -methylcinnamic acid; acetophenone; beta -hydroxy acetophenone; 2,3-dihydroxy benzoic acid and succinic acid. From these intermediates a new degradation pathway for sec -octylbenzene was investigated. Our results indicate that N. cyriacigeorgica has the ability to degrade aliphatic and branched chain alkanes as well as alkylbenzene effectively and, therefore, N. cyriacigeorgica is probably a suitable bacterium for biodegradation of oil or petroleum products in contaminated soils. ((c) 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).

Cellular Localization and Trafficking of the Human ABCG1 Transporter

PubMed Central

Neufeld, Edward B.; O’Brien, Katherine; Walts, Avram D.; Stonik, John A.; Demosky, Steven J.; Malide, Daniela; Combs, Christian A.; Remaley, Alan T.

2014-01-01

We have developed a suitable heterologous cell expression system to study the localization, trafficking, and site(s) of function of the human ABCG1 transporter. Increased plasma membrane (PM) and late endosomal (LE) cholesterol generated by ABCG1 was removed by lipoproteins and liposomes, but not apoA-I. Delivery of ABCG1 to the PM and LE was required for ABCG1-mediated cellular cholesterol efflux. ABCG1 LEs frequently contacted the PM, providing a collisional mechanism for transfer of ABCG1-mobilized cholesterol, similar to ABCG1-mediated PM cholesterol efflux to lipoproteins. ABCG1-mobilized LE cholesterol also trafficked to the PM by a non-vesicular pathway. Transfer of ABCG1-mobilized cholesterol from the cytoplasmic face of LEs to the PM and concomitant removal of cholesterol from the outer leaflet of the PM bilayer by extracellular acceptors suggests that ABCG1 mobilizes cholesterol on both sides of the lipid bilayer for removal by acceptors. ABCG1 increased uptake of HDL into LEs, consistent with a potential ABCG1-mediated cholesterol efflux pathway involving HDL resecretion. Thus, ABCG1 at the PM mobilizes PM cholesterol and ABCG1 in LE/LYS generates mobile pools of cholesterol that can traffic by both vesicular and non-vesicular pathways to the PM where it can also be transferred to extracellular acceptors with a lipid surface. PMID:25405320

Systematic evaluation of RNA quality, microarray data reliability and pathway analysis in fresh, fresh frozen and formalin-fixed paraffin-embedded tissue samples.

PubMed

Wimmer, Isabella; Tröscher, Anna R; Brunner, Florian; Rubino, Stephen J; Bien, Christian G; Weiner, Howard L; Lassmann, Hans; Bauer, Jan

2018-04-20

Formalin-fixed paraffin-embedded (FFPE) tissues are valuable resources commonly used in pathology. However, formalin fixation modifies nucleic acids challenging the isolation of high-quality RNA for genetic profiling. Here, we assessed feasibility and reliability of microarray studies analysing transcriptome data from fresh, fresh-frozen (FF) and FFPE tissues. We show that reproducible microarray data can be generated from only 2 ng FFPE-derived RNA. For RNA quality assessment, fragment size distribution (DV200) and qPCR proved most suitable. During RNA isolation, extending tissue lysis time to 10 hours reduced high-molecular-weight species, while additional incubation at 70 °C markedly increased RNA yields. Since FF- and FFPE-derived microarrays constitute different data entities, we used indirect measures to investigate gene signal variation and relative gene expression. Whole-genome analyses revealed high concordance rates, while reviewing on single-genes basis showed higher data variation in FFPE than FF arrays. Using an experimental model, gene set enrichment analysis (GSEA) of FFPE-derived microarrays and fresh tissue-derived RNA-Seq datasets yielded similarly affected pathways confirming the applicability of FFPE tissue in global gene expression analysis. Our study provides a workflow comprising RNA isolation, quality assessment and microarray profiling using minimal RNA input, thus enabling hypothesis-generating pathway analyses from limited amounts of precious, pathologically significant FFPE tissues.

Proceedings: international regulatory considerations on development pathways for cell therapies.

PubMed

Feigal, Ellen G; Tsokas, Katherine; Viswanathan, Sowmya; Zhang, Jiwen; Priest, Catherine; Pearce, Jonathan; Mount, Natalie

2014-08-01

Regenerative medicine is a rapidly evolving field that faces novel scientific and regulatory challenges. In September 2013, the International Workshop on Regulatory Pathways for Cell Therapies was convened to discuss the nature of these challenges and potential solutions and to highlight opportunities for potential convergence between different regulatory bodies that might assist the field's development. The workshop discussions generated potentially actionable steps in five main areas that could mitigate cell therapy development pathway risk and accelerate moving promising therapies to patients. These included the need for convergence of regulatory guidelines on donor eligibility and suitability of lines for use in clinical trials and subsequent commercialization for cell therapies to move forward on a global basis; the need to challenge and encourage investigators in the regenerative medicine field to share information and provide examples of comparability studies related to master cell banks; the need for convergence of guidelines across regulatory jurisdictions on requirements for tumorigenicity studies, based on particular cell types and on biodistribution studies; the need to increase transparency in sharing clinical trial information more broadly and disseminating results more rapidly; and the need to establish a forum for sharing the experiences of various approaches being developed to expedite regulatory approvals and access for patients to innovative cell and regenerative therapies in the different regulatory jurisdictions and to assess their potential strengths and weaknesses. ©AlphaMed Press.

Glucose Addiction in Cancer Therapy: Advances and Drawbacks.

PubMed

Granja, Sara; Pinheiro, Céline; Reis, Rui Manuel; Martinho, Olga; Baltazar, Fátima

2015-01-01

While normal differentiated cells primarily use mitochondrial respiration to generate the required energy for cellular processes, most cancer cells rely on glycolysis, even in sufficient oxygen conditions. This phenomenon is known as the "Warburg effect" or aerobic glycolysis and the metabolic reprogramming of cancer cells towards this altered energy metabolism is currently recognized as one of the "hallmarks of cancer". Aerobic glycolysis underlies the rapid growth of tumor cells, with high rates of glucose consumption and lactic acid production, leading to cellular acidosis. Metabolic reprogramming renders cancer cells dependent on specific metabolic enzymes or pathways that could be exploited in cancer therapy. The development of treatments that target tumor glucose metabolism is receiving renewed attention, with several drugs targeting metabolic pathways currently in clinical trials. The search for suitable targets, however, is limited by the high plasticity of the metabolic network that can induce compensatory routes. Deregulated glucose metabolism is a prominent feature associated with resistance to classical chemotherapy or oncogene-targeted therapies, strengthening the clinical potential of combining these therapies with glycolysis inhibitors. The aim of this review is to compare the advances of different therapeutic strategies targeting the glucose "addiction" of tumor cells, highlighting their potential as effective weapons against cancer. We further discuss recent evidence for the involvement of glucose metabolism as a compensatory response to the use of drugs that target different signaling pathways, where the combination with glycolysis inhibitors could prove extraordinarily useful.

Antibiotic Combinations That Enable One-Step, Targeted Mutagenesis of Chromosomal Genes.

PubMed

Lee, Wonsik; Do, Truc; Zhang, Ge; Kahne, Daniel; Meredith, Timothy C; Walker, Suzanne

2018-06-08

Targeted modification of bacterial chromosomes is necessary to understand new drug targets, investigate virulence factors, elucidate cell physiology, and validate results of -omics-based approaches. For some bacteria, reverse genetics remains a major bottleneck to progress in research. Here, we describe a compound-centric strategy that combines new negative selection markers with known positive selection markers to achieve simple, efficient one-step genome engineering of bacterial chromosomes. The method was inspired by the observation that certain nonessential metabolic pathways contain essential late steps, suggesting that antibiotics targeting a late step can be used to select for the absence of genes that control flux into the pathway. Guided by this hypothesis, we have identified antibiotic/counterselectable markers to accelerate reverse engineering of two increasingly antibiotic-resistant pathogens, Staphylococcus aureus and Acinetobacter baumannii. For S. aureus, we used wall teichoic acid biosynthesis inhibitors to select for the absence of tarO and for A. baumannii, we used colistin to select for the absence of lpxC. We have obtained desired gene deletions, gene fusions, and promoter swaps in a single plating step with perfect efficiency. Our method can also be adapted to generate markerless deletions of genes using FLP recombinase. The tools described here will accelerate research on two important pathogens, and the concept we outline can be readily adapted to any organism for which a suitable target pathway can be identified.

Exploring innovative techniques for identifying geochemical elements as fingerprints of sediment sources in an agricultural catchment of Argentina affected by soil erosion.

PubMed

Torres Astorga, Romina; de Los Santos Villalobos, Sergio; Velasco, Hugo; Domínguez-Quintero, Olgioly; Pereira Cardoso, Renan; Meigikos Dos Anjos, Roberto; Diawara, Yacouba; Dercon, Gerd; Mabit, Lionel

2018-05-15

Identification of hot spots of land degradation is strongly related with the selection of soil tracers for sediment pathways. This research proposes the complementary and integrated application of two analytical techniques to select the most suitable fingerprint tracers for identifying the main sources of sediments in an agricultural catchment located in Central Argentina with erosive loess soils. Diffuse reflectance Fourier transformed in the mid-infrared range (DRIFT-MIR) spectroscopy and energy-dispersive X-ray fluorescence (EDXRF) were used for a suitable fingerprint selection. For using DRIFT-MIR spectroscopy as fingerprinting technique, calibration through quantitative parameters is needed to link and correlate DRIFT-MIR spectra with soil tracers. EDXRF was used in this context for determining the concentrations of geochemical elements in soil samples. The selected tracers were confirmed using two artificial mixtures composed of known proportions of soil collected in different sites with distinctive soil uses. These fingerprint elements were used as parameters to build a predictive model with the whole set of DRIFT-MIR spectra. Fingerprint elements such as phosphorus, iron, calcium, barium, and titanium were identified for obtaining a suitable reconstruction of the source proportions in the artificial mixtures. Mid-infrared spectra produced successful prediction models (R 2  = 0.91) for Fe content and moderate useful prediction (R 2  = 0.72) for Ti content. For Ca, P, and Ba, the R 2 were 0.44, 0.58, and 0.59 respectively.

[Study on Precursors for Synthesis of Anthraquinone Metabolites from Rheum tanguticum].

PubMed

Hasi, Qi-mei-ge; Lj, Hai-ling; Cheng, Yan; Menggen, Qi-qi-ge; Zhang, Yang

2015-01-01

To explore the potential precursors of the anthraquinone metabolites from Rheum tanguticum and preliminanly identify the synthesis pathway thereof. Sterile seedlings sprouted from the seeds of Rheum tanguticum were chosen as materials for inducing callus. The effects of different precursors and feeding duration on the callus of Rheum tanguticum and the anthraquinone yield in adult rheum were studied. The greatest improvement of anthraquinone yield was achieved by acetic acid, increasing 43. 9% for the callus and 45. 8% in the adult rheum; the second greatest improvement was achieved by malonic acid, increasing 15. 8% for the callus and only 3. 6% in the adult rheum. The yield of anthraquinone was not influenced significantly by benzoic acid and p-benzoquinone, and in contrast, was inhibited in some degree by shikimic acid and α-ketoglutaric acid. A suitable feeding duration was 36 h, which worked well for the effects of precursors. The precursor for synthesis of anthraquinone metabolites from Rheum tan- guticum is acetic acid, which improves the yields of callus and anthraquinone in adult rheum, concluding that the anthraquinone metabolites are synthesized via polyketone pathway.

Does Thioflavin-T Detect Oligomers Formed During Amyloid Fibril Assembly

NASA Astrophysics Data System (ADS)

Persichilli, Christopher; Hill, Shannon E.; Mast, Jason; Muschol, Martin

2011-03-01

Recent results have shown that oligomeric intermediates of amyloid fibril assembly represent the main toxic species in disorders such as Alzheimer's disease and type II diabetes. Thioflavin-T (ThT) is among the most commonly used indicator dyes for mature amyloid fibrils in vitro. We used ThT to monitor amyloid fibril formation of lysozyme (HEWL), and correlated ThT fluorescence to concurrent dynamic light scattering and atomic force microscopy measurements. Specifically, we tested the ability of ThT to discern among oligomer-free vs. oligomeric fibril assembly pathways. We found that ThT fluorescence did not detect oligomer growth; however, fluorescence increases did coincide with the formation of monomeric filaments in the oligomer-free assembly pathway. This implies that ThT fluorescence is not generally suitable for the detection of oligomeric intermediates. The results further suggest different internal structures for oligomeric vs. monomeric filaments. This research was supported, in part, by funding through the Byrd Alzheimer's Institute (ARG-2007-22) and the BITT-Florida Center of Excellence for M.M., an NSF-REU grant (DMR-1004873) for C. P. and an NSF-IGERT fellowship for S.H.

Reducing Recon 2 for steady-state flux analysis of HEK cell culture.

PubMed

Quek, Lake-Ee; Dietmair, Stefanie; Hanscho, Michael; Martínez, Verónica S; Borth, Nicole; Nielsen, Lars K

2014-08-20

A representative stoichiometric model is essential to perform metabolic flux analysis (MFA) using experimentally measured consumption (or production) rates as constraints. For Human Embryonic Kidney (HEK) cell culture, there is the opportunity to use an extremely well-curated and annotated human genome-scale model Recon 2 for MFA. Performing MFA using Recon 2 without any modification would have implied that cells have access to all functionality encoded by the genome, which is not realistic. The majority of intracellular fluxes are poorly determined as only extracellular exchange rates are measured. This is compounded by the fact that there is no suitable metabolic objective function to suppress non-specific fluxes. We devised a heuristic to systematically reduce Recon 2 to emphasize flux through core metabolic reactions. This implies that cells would engage these dominant metabolic pathways to grow, and any significant changes in gross metabolic phenotypes would have invoked changes in these pathways. The reduced metabolic model becomes a functionalized version of Recon 2 used for identifying significant metabolic changes in cells by flux analysis. Copyright © 2014 Elsevier B.V. All rights reserved.

In search of a viable reaction pathway in the chelation of a metallo-protein

NASA Astrophysics Data System (ADS)

Rose, Frisco; Hodak, Miroslav; Bernholc, Jerry

2010-03-01

Misfolded metallo-proteins are potential causal agents in the onset of neuro-degenerative diseases, such as Alzheimer's and Parkinson's Diseases (PD). Experimental results involving metal chelation have shown significant promise in symptom reduction and misfolding reversal. We explore, through atomistic simulations, potential reaction pathways for the chelation of Cu^2+ from the metal binding site in our representation of a partially misfolded α-synuclein, the protein implicated in PD. Our ab initio simulations use Density Functional Theory (DFT) and nudged elastic band to obtain the minimized energy coordinates of this reaction. Our simulations include ab initio water at the interaction site and in its first solvation shells, while the remainder is fully solvated with orbital-free DFT water representation [1]. Our ongoing studies of viable chelation agents include nicotine, caffeine and other potential reagents, we will review the best case agents in this presentation. [4pt] [1] Hodak M, Lu W, Bernholc J. Hybrid ab initio Kohn-Sham density functional theory/frozen-density orbital-free density functional theory simulation method suitable for biological systems. J. Chem. Phys. 2008 Jan;128(1):014101-9.

Hypoxia-responsive miRNAs target argonaute 1 to promote angiogenesis

PubMed Central

Chen, Zhen; Lai, Tsung-Ching; Jan, Yi-Hua; Lin, Feng-Mao; Wang, Wei-Chi; Xiao, Han; Wang, Yun-Ting; Sun, Wei; Cui, Xiaopei; Li, Ying-Shiuan; Fang, Tzan; Zhao, Hongwei; Padmanabhan, Chellappan; Sun, Ruobai; Wang, Danny Ling; Jin, Hailing; Chau, Gar-Yang; Huang, Hsien-Da; Hsiao, Michael; Shyy, John Y-J.

2013-01-01

Despite a general repression of translation under hypoxia, cells selectively upregulate a set of hypoxia-inducible genes. Results from deep sequencing revealed that Let-7 and miR-103/107 are hypoxia-responsive microRNAs (HRMs) that are strongly induced in vascular endothelial cells. In silico bioinformatics and in vitro validation showed that these HRMs are induced by HIF1α and target argonaute 1 (AGO1), which anchors the microRNA-induced silencing complex (miRISC). HRM targeting of AGO1 resulted in the translational desuppression of VEGF mRNA. Inhibition of HRM or overexpression of AGO1 without the 3′ untranslated region decreased hypoxia-induced angiogenesis. Conversely, AGO1 knockdown increased angiogenesis under normoxia in vivo. In addition, data from tumor xenografts and human cancer specimens indicate that AGO1-mediated translational desuppression of VEGF may be associated with tumor angiogenesis and poor prognosis. These findings provide evidence for an angiogenic pathway involving HRMs that target AGO1 and suggest that this pathway may be a suitable target for anti- or proangiogenesis strategies. PMID:23426184

Ligand-Induced Modulation of the Free-Energy Landscape of G Protein-Coupled Receptors Explored by Adaptive Biasing Techniques

PubMed Central

Provasi, Davide; Artacho, Marta Camacho; Negri, Ana; Mobarec, Juan Carlos; Filizola, Marta

2011-01-01

Extensive experimental information supports the formation of ligand-specific conformations of G protein-coupled receptors (GPCRs) as a possible molecular basis for their functional selectivity for signaling pathways. Taking advantage of the recently published inactive and active crystal structures of GPCRs, we have implemented an all-atom computational strategy that combines different adaptive biasing techniques to identify ligand-specific conformations along pre-determined activation pathways. Using the prototypic GPCR β2-adrenergic receptor as a suitable test case for validation, we show that ligands with different efficacies (either inverse agonists, neutral antagonists, or agonists) modulate the free-energy landscape of the receptor by shifting the conformational equilibrium towards active or inactive conformations depending on their elicited physiological response. Notably, we provide for the first time a quantitative description of the thermodynamics of the receptor in an explicit atomistic environment, which accounts for the receptor basal activity and the stabilization of different active-like states by differently potent agonists. Structural inspection of these metastable states reveals unique conformations of the receptor that may have been difficult to retrieve experimentally. PMID:22022248

Discovery of Regulators of Receptor Internalization with High-Throughput Flow Cytometry

PubMed Central

Tapia, Phillip H.; Fisher, Gregory W.; Simons, Peter C.; Strouse, J. Jacob; Foutz, Terry; Waggoner, Alan S.; Jarvik, Jonathan; Sklar, Larry A.

2012-01-01

We developed a platform combining fluorogen-activating protein (FAP) technology with high-throughput flow cytometry to detect real-time protein trafficking to and from the plasma membrane in living cells. The hybrid platform facilitates drug discovery for trafficking receptors such as G protein-coupled receptors and was validated with the β2-adrenergic receptor (β2AR) system. When a chemical library containing ∼1200 off-patent drugs was screened against cells expressing FAP-tagged β2ARs, all 33 known β2AR-active ligands in the library were successfully identified, together with a number of compounds that might regulate receptor internalization in a nontraditional manner. Results indicated that the platform identified ligands of target proteins regardless of the associated signaling pathway; therefore, this approach presents opportunities to search for biased receptor modulators and is suitable for screening of multiplexed targets for improved efficiency. The results revealed that ligands may be biased with respect to the rate or duration of receptor internalization and that receptor internalization may be independent of activation of the mitogen-activated protein kinase pathway. PMID:22767611

CVD and Oxidative Stress

PubMed Central

Cervantes Gracia, Karla; Llanas-Cornejo, Daniel; Husi, Holger

2017-01-01

Nowadays, it is known that oxidative stress plays at least two roles within the cell, the generation of cellular damage and the involvement in several signaling pathways in its balanced normal state. So far, a substantial amount of time and effort has been expended in the search for a clear link between cardiovascular disease (CVD) and the effects of oxidative stress. Here, we present an overview of the different sources and types of reactive oxygen species in CVD, highlight the relationship between CVD and oxidative stress and discuss the most prominent molecules that play an important role in CVD pathophysiology. Details are given regarding common pharmacological treatments used for cardiovascular distress and how some of them are acting upon ROS-related pathways and molecules. Novel therapies, recently proposed ROS biomarkers, as well as future challenges in the field are addressed. It is apparent that the search for a better understanding of how ROS are contributing to the pathophysiology of CVD is far from over, and new approaches and more suitable biomarkers are needed for the latter to be accomplished. PMID:28230726

Hyperdynamics boost factor achievable with an ideal bias potential

DOE PAGES

Huang, Chen; Perez, Danny; Voter, Arthur F.

2015-08-20

Hyperdynamics is a powerful method to significantly extend the time scales amenable to molecular dynamics simulation of infrequent events. One outstanding challenge, however, is the development of the so-called bias potential required by the method. In this work, we design a bias potential using information about all minimum energy pathways (MEPs) out of the current state. While this approach is not suitable for use in an actual hyperdynamics simulation, because the pathways are generally not known in advance, it allows us to show that it is possible to come very close to the theoretical boost limit of hyperdynamics while maintainingmore » high accuracy. We demonstrate this by applying this MEP-based hyperdynamics (MEP-HD) to metallic surface diffusion systems. In most cases, MEP-HD gives boost factors that are orders of magnitude larger than the best existing bias potential, indicating that further development of hyperdynamics bias potentials could have a significant payoff. Lastly, we discuss potential practical uses of MEP-HD, including the possibility of developing MEP-HD into a true hyperdynamics.« less