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941.
Systems Biology involves the study of the interactions of biological systems and ultimately their functions. Down''s syndrome (DS)
is one of the most common genetic disorders which are caused by complete, or occasionally partial, triplication of chromosome 21,
characterized by cognitive and language dysfunction coupled with sensory and neuromotor deficits. Neural Tube Disorders
(NTDs) are a group of congenital malformations of the central nervous system and neighboring structures related to defective
neural tube closure during the first trimester of pregnancy usually occurring between days 18-29 of gestation. Several studies in the
past have provided considerable evidence that abnormal folate and methyl metabolism are associated with onset of DS & NTDs.
There is a possible common etiological pathway for both NTDs and Down''s syndrome. But, various research studies over the years
have indicated very little evidence for familial link between the two disorders. Our research aimed at the gene expression profiling
of microarray datasets pertaining to the two disorders to identify genes whose expression levels are significantly altered in these
conditions. The genes which were 1.5 fold unregulated and having a p-value <0.05 were filtered out and gene interaction network
were constructed for both NTDs and DS. The top ranked dense clique for both the disorders were recognized and over
representation analysis was carried out for each of the constituent genes. The comprehensive manual analysis of these genes yields
a hypothetical understanding of the lack of familial link between DS and NTDs. There were no genes involved with folic acid
present in the dense cliques. Only – CBL, EGFR genes were commonly present, which makes the allelic variants of these genes –
good candidates for future studies regarding the familial link between DS and NTDs.
Abbreviations
NTD - Neural Tube Disorders, DS - Down''s Syndrome, MTHFR - Methylenetetrahydrofolate reductase, MTRR– 5 - methyltetrahydrofolate-homocysteine methyltransferase reductase. 相似文献942.
Clifford H. Keller Masashi Kawasaki Walter Heiligenberg 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1991,169(4):441-450
Summary Nearly sinusoidal electric organ discharges (EODs) of the weakly electric fish Sternopygus, occur at a regular rate within a range from 50 to 200 Hz and are commanded by a medullary pacemaker nucleus (Pn). During courtship and aggression, the rate of EODs is modulated as smooth EOD-frequency rises or brief EOD-interruptions (Hopkins 1974b). The present study examines the control of such modulations. Rises were elicited by L-glutamate stimulation of the diencephalic prepacemaker nucleus, the only previously known source of input to the Pn. We demonstrate an additional input to the Pn, the sublemniscal prepacemaker nucleus (SPPn). L-glutamate stimulation of this area caused EOD-interruptions.The Pn contains electrotonically coupled pacemaker cells which generate the rhythm of the EODs, as well as relay cells which transmit the command pulse to the spinal motor neurons that innervate the electric organ. Pacemaker cells recorded intracellularly during EOD-interruptions continued firing at their regular frequency but with slightly increased jitter. Relay cells, on the other hand, were strongly depolarized and fired spikelets at a greatly increased frequency during EOD-interruptions. Thus EOD-interruptions were caused by SPPn input to relay cells that caused their massive depolarization, blocking the normal input from pacemaker cells without greatly affecting pacemaker cell firing characteristics.Application to the Pn of an antagonist to NMDA-type glutamate receptors blocked EOD-frequency rises and EOD-interruptions. Antagonists to quisqualate/ kainate receptor-types were ineffective.Abbreviations
EOD
Electric Organ Discharge
-
JAR
Jamming Avoidance Response
-
Pn
pacemaker nucleus
-
PPn
diencephalic prepacemaker nucleus
-
SPPn
sublemniscal prepacemaker nucleus 相似文献
943.
Ito H Ishida H Collins BE Fromholt SE Schnaar RL Kiso M 《Carbohydrate research》2003,338(16):1621-1639
Systematic synthesis and myelin-associated glycoprotein (MAG)-binding activity of novel sulfated GM1b analogues structurally related to Chol-1 (alpha-series) gangliosides, high-affinity ligands for neural siglecs, are described. The suitably protected gangliotriose derivatives, 2-(trimethylsilyl)ethyl 2-acetamido-2-deoxy-6-O-levulinoyl-beta-D-galactopyranosyl-(1-->4)-2,3,6-tri-O-benzyl-beta-D-galactopyranosyl-(1-->4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside and 2-(trimethylsilyl)ethyl 2-acetamido-2-deoxy-6-O-levulinoyl-beta-D-galactopyranosyl-(1-->4)-2,6-di-O-benzyl-3-O-levulinoyl-beta-D-galactopyranosyl-(1-->4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside were each glycosylated with alpha-NeuAc-(2-->3)-galactose donor to give the corresponding pentasaccharides in 94% (beta1,3 glycoside only) and 90% (beta1,3:beta1,4 = 2:1), respectively. After proper manipulation of the protecting groups, the pentasaccharides were converted into three novel sulfated GM1b gangliosides by the successive introduction of the ceramide and sulfo groups, followed by complete deprotection. Among the synthetic gangliosides, GSC-338 (II3III6-disulfate of iso-GM1b) was surprisingly found to be the most potent MAG binding structure tested to date. 相似文献
944.
Raymund E. Horch Justus P. Beier Ulrich Kneser Andreas Arkudas 《Journal of cellular and molecular medicine》2014,18(7):1478-1485
Tissue Engineering (TE) and Regenerative Medicine (RM) have gained much popularity because of the tremendous prospects for the care of patients with tissue and organ defects. To overcome the common problem of donor‐site morbidity of standard autologous bone grafts, we successfully combined tissue engineering techniques for the first time with the arteriovenous loop model to generate vascularized large bone grafts. We present two cases of large bone defects after debridement of an osteomyelitis. One of the defects was localized in the radius and one in the tibia. For osseus reconstruction, arteriovenous loops were created as vascular axis, which were placed in the bony defects. In case 1, the bone generation was achieved using cancellous bone from the iliac crest and fibrin glue and in case 2 using a clinically approved β‐tricalciumphosphate/hydroxyapatite (HA), fibrin glue and directly auto‐transplanted bone marrow aspirate from the iliac crest. The following post‐operative courses were uneventful. The final examinations took place after 36 and 72 months after the initial operations. Computer tomogrphy (CT), membrane resonance imaging (MRI) and doppler ultrasound revealed patent arterio‐venous (AV) loops in the bone grafts as well as completely healed bone defects. The patients were pain‐free with normal ranges of motion. This is the first study demonstrating successfully axially vascularized in situ tissue engineered bone generation in large bone defects in a clinical scenario using the arteriovenous loop model without creation of a significant donor‐site defect utilizing TE and RM techniques in human patients with long‐term stability. 相似文献
945.
946.
Wakako Yamada Kenji Nagao Ayako Fujikura Yoshimasa Inagaki Kazuma Tomizuka Toshio Suda Keiyo Takubo 《Biochemical and biophysical research communications》2009,381(3):453-458
In vertebrates, craniofacial formation is accomplished by synergistic interaction of many small elements which are generated independently from distinct germ layers. Because of its complexity, the imbalance of one signaling cascade such as Wnt/β-catenin pathway easily leads to craniofacial malformation, which is the most frequent birth defect in humans. To investigate the developmental role of a newly identified activator of Wnt/β-catenin signaling, Rspo2, we generated and characterized Rspo2−/− mice. We found CLP with mild facial skeletal defects in Rspo2−/− mice. Additionally, Rspo2−/− mice also exhibited distal limb loss and lung hypoplasia, and died immediately after birth with respiratory failure. We showed the apparent reduction of Wnt/β-catenin signaling activity at the branchial arch and the apical ectodermal ridge in Rspo2−/− mice. These findings indicate that Rspo2 regulates midfacial, limb, and lung morphogenesis during development through the Wnt/β-catenin signaling. 相似文献
947.
Neural crest-derived pigment cell development has been used extensively to study cell fate specification, migration, proliferation, survival and differentiation. Many of the genes and regulatory mechanisms required for pigment cell development are conserved across vertebrates. The zebrafish mutant colgate (col)/histone deacetylase1 (hdac1) has reduced numbers, delayed differentiation and decreased migration of neural crest-derived melanophores and their precursors. In hdac1col mutants normal numbers of premigratory neural crest cells are induced. Later, while there is only a slight reduction in the number of neural crest cells in hdac1col mutants, there is a severe reduction in the number of mitfa-positive melanoblasts suggesting that hdac1 is required for melanoblast specification. Concomitantly, there is a significant increase in and prolonged expression of foxd3 in neural crest cells in hdac1col mutants. We found that partially reducing Foxd3 expression in hdac1col mutants rescues mitfa expression and the melanophore defects in hdac1col mutants. Furthermore, we demonstrate the ability of Foxd3 to physically interact at the mitfa promoter. Because mitfa is required for melanoblast specification and development, our results suggest that hdac1 is normally required to suppress neural crest foxd3 expression thus de-repressing mitfa resulting in melanogenesis by a subset of neural crest-derived cells. 相似文献
948.
Jonathan M. Blagburn Rosa E. Blanco Kevin S. J. Thompson Jonathan P. Bacon 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1991,169(5):607-614
Summary Mutant first instar cockroaches (Periplaneta americana) with supernumerary filiform hair sensilla on their cerci were used to study the effects of cell body position on axonal morphology and synaptic connections. The wild-type cercus has two hairs, one lateral (L) and the other medial (M), each with an underlying sensory neuron. Silver-intensified cobalt fills show that the supernumerary lateral neuron (SIN) in the mutant has the same shape of arborization as L, and electrophysiological recording shows that it forms synaptic connections with the same subset of giant interneurons (GIs) as L in the terminal ganglion: GI3 and GI6. The supernumerary medial neuron (SuM) has the same axonal morphology as M and synapses with the same GIs as does M: ipsilateral GIs 1 and 2 and contralateral GIs 1, 2, 3, 5 and 6. In 0.1% of approximately 8000 animals screened, a supernumerary hair arose on the cereal midline (C hair). The C neuron sends its axon to the CNS in the same branch of the cereal nerve as the L and SIN, and has a similar arborization. However, the C neuron forms synapses with the same GIs as do M and SuM. Electron microscopy of horseradish peroxidase-injected neurons was used to confirm that the C afferent forms a monosynaptic connection to GI2. It was concluded that the position of the sensory neuron cell body does control its axonal morphology and synaptic connectivity, but that these characteristics are produced by independent mechanisms.Abbreviations
GI
giant interneuron
-
L
lateral
-
M
medial
-
SI
Space Invader
-
SuM
supernumerary medial
-
C
cereal midline 相似文献
949.
海马记忆功能的神经网络模型 总被引:2,自引:0,他引:2
综合神经心理学,神经生理学、解剖学与神经网络研究的成果,提出一个海马记忆功能的神经网络模型。模型由三个神经网络所组成;海马的CA1和CA3网络和大脑皮层联合区,CA3的功能是将不同感觉输入联合起来,而CA1的作用是将它们结成一个单一的记忆。而大脑皮层则是长期记忆的部位。在VAX11/750上进行计算机仿真,仿真证明模型有近期及长期记忆功能,破坏模拟海马的部分,模型显示出与顺行性遗忘症相似的特性。在 相似文献
950.
Marco Skardelly Anja Glien Claudia Groba Nadine Schlichting Manja Kamprad Juergen Meixensberger Javorina Milosevic 《Experimental cell research》2013,319(20):3170-3181
In allogenic and xenogenic transplantation, adequate immunosuppression plays a major role in graft survival, especially over the long term. The effect of immunosuppressive drugs on neural stem/progenitor cell fate has not been sufficiently explored. The focus of this study is to systematically investigate the effects of the following four different immunotherapeutic strategies on human neural progenitor cell survival/death, proliferation, metabolic activity, differentiation and migration in vitro: (1) cyclosporine A (CsA), a calcineurin inhibitor; (2) everolimus (RAD001), an mTOR-inhibitor; (3) mycophenolic acid (MPA, mycophenolate), an inhibitor of inosine monophosphate dehydrogenase and (4) prednisolone, a steroid. At the minimum effective concentration (MEC), we found a prominent decrease in hNPCs' proliferative capacity (BrdU incorporation), especially for CsA and MPA, and an alteration of the NAD(P)H-dependent metabolic activity. Cell death rate, neurogenesis, gliogenesis and cell migration remained mostly unaffected under these conditions for all four immunosuppressants, except for apoptotic cell death, which was significantly increased by MPA treatment. 相似文献