Interlocked and interdigitated architectures from self-assembly of long flexible ligands and cadmium salts.
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Cadmium↗
Biomedical subjects
Lin Xu
Publications and source records attributed to Lin Xu.
Properties of the proton-evoked currents and their modulation by Ca2+ and Zn2+ in the acutely dissociated hippocampus CA1 neurons.
The characterization of acid-sensing ion channel (ASIC)-like currents has been reported in hippocampal neurons in primary culture. However, it is suggested that the profile of expression of ASICs changes in culture. In this study, we investigated the properties of proton-activated current and its modulation by extracellular Ca(2+) and Zn(2+) in neurons acutely dissociated from the rat hippocampal CA1 using conventional whole-cell patch-clamp recording. A rapidly decaying inward current and membrane depolarization was induced by exogenous application of acidic solution. The current was sensitive to the extracellular proton with a response threshold of pH 7.0-6.8 and the pH(50) of 6.1, the reversal potential close to the Na(+) equilibrium potential. It had a characteristic of acid-sensing ion channels (ASICs) as demonstrated by its sensitivity to amiloride (IC(50)=19.6+/-2.1 microM). Either low [Ca(2+)](o) or high [Zn(2+)](o) increased the amplitude of the current. All these characteristics are consistent with a current mediated through a mixture of homomeric ASIC1a and heteromeric ASIC1a+2a channels and closely replicate many of the characteristics that have been previously reported for hippocampal neurons cultured for a week or more, indicating that culture artifacts do not necessarily flaw the properties of ASICs. Interestingly, we found that high [Zn(2+)](o) (>10(-4) M) slowed the decay time constant of the ASIC-like current significantly in both acutely dissociated and cultured hippocampal neurons. In addition, the facilitating effects of low [Ca(2+)](o) and high [Zn(2+)](o) on the ASIC-like current were not additive. Since tissue acidosis, extracellular Zn(2+) elevation and/or Ca(2+) reduction occur concurrently under some physiological and/or pathological conditions, the present observations suggest that hippocampal ASICs may offer a novel pharmacological target for therapeutic invention.
Acid Sensing Ion Channels↗
Characterization of acid-sensing ion channels in dorsal horn neurons of rat spinal cord.
Acid-sensing ion channels (ASICs) are ligand-gated cation channels activated by extracellular protons. In periphery, they contribute to sensory transmission, including that of nociception and pain. Here we characterized ASIC-like currents in dorsal horn neurons of the rat spinal cord and their functional modulation in pathological conditions. Reverse transcriptase-nested PCR and Western blotting showed that three ASIC isoforms, ASIC1a, ASIC2a, and ASIC2b, are expressed at a high level in dorsal horn neurons. Electrophysiological and pharmacological properties of the proton-gated currents suggest that homomeric ASIC1a and/or heteromeric ASIC1a + 2b channels are responsible for the proton-induced currents in the majority of dorsal horn neurons. Acidification-induced action potentials in these neurons were compatible in a pH-dependent manner with the pH dependence of ASIC-like current. Furthermore, peripheral complete Freund's adjuvant-induced inflammation resulted in increased expression of both ASIC1a and ASIC2a in dorsal horn. These results support the idea that the ASICs of dorsal horn neurons participate in central sensory transmission/modulation under physiological conditions and may play important roles in inflammation-related persistent pain.
Acid Sensing Ion Channels↗
[The effective analysis on clearance of pararectal lymph nodes for carcinoma of rectum].
OBJECTIVE: To consider the relationship to survival rate and quality of life with pararectal lymphadenectomy for lower carcinoma of rectum. METHODS: The radical operation was performed on 780 cases of progressive cancer located at peritoneal reflection or below it, Among them, 352 cases only cleared in abdominal cavity, 428 cases coupled with extra-peritoneal histopathological type. RESULTS: Urinary function injured, the group cleared in abdominal cavity was 12 cases, accounted for 3.6%; the group coupled with extra-peritoneal clearance was 225 cases, for 52.5% (P < 0.01). Sexual function damaged (only for male), the abdominal cavity group was 23 cases, for 12.6% (23/185); the coupled group was 127 cases, for 53.4% (127/238), (P < 0.01). Local relapse rate, the abdominal cavity group was 15.8% (56/352); the coupled group was 8.6% (41/428), (P < 0.05). 5-year survival rate, the abdominal cavity group was 52.2%; the coupled group was 58.5% (P < 0.05). CONCLUSION: By contrast, although abdominal cavity coupled with extraperitoneal lymphadenectomy acted to cut down local relapse and to elevate 5-year survival rate, the postoperative quality of life appeared to be seriously affected.
Female↗
Intracerebral transplantation of carotid body in rats with transient middle cerebral artery occlusion.
Recent laboratory and clinical studies demonstrate therapeutic efficacy of intracerebral transplantation of carotid body (CB) in Parkinson's disease, possibly through secretion of neurotrophic factors. Here, we examined the role of CB in experimental stroke. In the first experiment, we hypothesized that removal of CB would exacerbate cerebral infarction and stroke-related behavioral deficits. Eight-week-old, male Sprague-Dawley rats were randomly divided into two groups: stroke with intact CB and stroke with surgically removed CB. We used the stroke model of temporary middle cerebral artery occlusion. The ipsilateral CB was removed in animals assigned to treatment group exposed to stroke with surgically removed CB. Behavioral tests, using the elevated body swing test, were conducted at days 1-3 after surgery. Cerebral infarction was visualized by TTC staining on day 3 post-surgery. The data revealed no significant differences in behavioral deficits and infarct volumes between the two groups. In the second experiment, CB cell suspension grafts or control adult tissue grafts were intracerebally transplanted into the ischemic penumbra immediately (within 1 h) after stroke surgery. The results revealed significant reduction of behavioral deficits and infarct volumes, accompanied by increased levels of neurotrophic factors, as detected by ELISA, in transplanted ischemic striatum collected from CB-grafted stroke animals. These observations suggest that surgical resection of CB in the periphery did not alter stroke pathology; however, CB when made available in the CNS, via intracerebral transplantation, could protect against stroke possibly through the synergistic release of neurotrophic factors. The present study extends the use of CB as efficacious graft source for transplantation.
Analysis of Variance↗
Photochromic inorganic-organic multilayer films based on polyoxometalates and poly(ethylenimine).
Novel photochromic inorganic-organic multilayers composed of polyoxometalates and poly(ethylenimine) have been prepared by the layer-by-layer (LbL) self-assembly method. The growth process, composition, surface topography, and photochromic properties of the multilayer films were investigated by UV-visible and Fourier transform infrared spectroscopy, atomic force microscopy, electrospin resonance (ESR), and X-ray photoelectron spectroscopy (XPS). Irradiated with ultraviolet light, the transparent films changed from colorless to blue. Moreover, the blue films showed good reversibility of photochromism and could recover the colorless state gradually in air, where oxygen plays an important role in the bleaching process. On account of the ESR and XPS results, parts of W6+ in multilayers were reduced to W5+, which exhibited a characteristic blue; a possible photochromic mechanism can be speculated. This work provides basic guideline for the assembly of multilayers with photochromic properties.
Journal Article↗
From arm-shaped layers to a new type of polythreaded array: a two fold interpenetrated three-dimensional network with a rutile topology.
The self-assembly based on 2D motifs with side arms leads to the formation of a new type of polythreaded network which exhibits a 2-fold interpenetrated 3D array if H-bonds are taken into account.
Journal Article↗
beta-Amyloid directly inhibits human alpha4beta2-nicotinic acetylcholine receptors heterologously expressed in human SH-EP1 cells.
Amyloid-beta (Abeta) accumulation and aggregation are thought to contribute to the pathogenesis of Alzheimer's disease (AD). In AD, there is a selective decrease in the numbers of radioligand binding sites corresponding to the most abundant nicotinic acetylcholine receptor (nAChR) subtype, which contains human alpha4 and beta2 subunits (halpha4beta2-nAChR). However, the relationships between these phenomena are uncertain, and effects of Abeta on halpha4beta2-nAChR function have not been investigated in detail. We first confirmed expression of halpha4 and hbeta2 subunits as messenger RNA in transfected, human SHEP1 cells by reverse transcription-polymerase chain reaction and mRNA fluorescence in situ hybridization analyses. Immunoprecipitation Western analyses confirmed alpha4 and beta2 subunit protein expression and co-assembly. Whole cell current recording demonstrated heterologous expression in SH-EP1-halpha4beta2 cells of functional halpha4beta2-nAChRs with characteristic responses to nicotinic agonists or antagonists. Nicotine-induced whole cell currents were suppressed by Abeta(1-42) in a dose-dependent manner. Functional inhibition was selective for Abeta(1-42) compared with the functionally inactive, control peptide Abeta(40-1).Abeta(1-42)-mediated inhibition of halpha4beta2-nAChR function was non-competitive, voltage-independent, and use-independent. Pre-loading of cells with guanyl-5'-yl thiophosphate failed to prevent Abeta(1-42)-induced inhibition, suggesting that down-regulation of halpha4beta2-nAChR function by Abeta(1-42) is not mediated by nAChR internalization. Sensitivity to Abeta(1-42) antagonism at 1 nm was evident for halpha4beta2-nAChRs, but not for heterologously expressed human alpha7-nAChRs, although both nAChR subtypes were functionally inhibited by 100 nm Abeta(1-42), with the magnitude of functional block being higher for 100 nm Abeta(1-42) acting on halpha7-nAChRs. These findings suggest that halpha4beta2-nAChRs are sensitive and perhaps pathophysiologically relevant targets for Abeta neurotoxicity in AD.
Amyloid↗
Synthesis and characterization of ultrathin multilayer films based on molybdenum polyoxometalate (Mo(54)).
The crown-shaped molybdenum polyoxometalate cluster Na(26)[[Na(H(2)O)(2)](6)[(micro(3) -OH)(4) (Mo(20)(V)), (Mo(34)(VI)(O)(164) (micro-CH(3)COO(4)) x 120H(2)O(Mo(54)) was synthesized and first used as a bulk modifier to fabricate a three-dimensional modified WIGE electrode by the layer-by-layer method. The (Mo(54))/PAH)(n) multilayer films have been characterized by X-ray photoelectron spectra (XPS) and atomic force microscopy (AFM). UV-vis measurements reveal regular film growth with each Mo(54) adsorption. The electrochemical method was used to characterize the modified WIGE electrode, which is important for practical applications.
Journal Article↗
Electrophysiological, pharmacological, and molecular evidence for alpha7-nicotinic acetylcholine receptors in rat midbrain dopamine neurons.
Dopamine (DA) neurons located in the mammalian midbrain have been generally implicated in reward and drug reinforcement and more specifically in nicotine dependence. However, roles played by nicotinic acetylcholine receptors, including those composed of alpha7-subunits [alpha7-nicotinic acetylcholine receptors (nAChRs)], in modulation of DA signaling and in nicotine dependence are not clearly understood. Although midbrain slice recording has been used previously to identify functional alpha7-nAChRs, these preparations are not optimally designed for extremely rapid and reproducible drug application, and rapidly desensitized, alpha7-nAChR-mediated currents may have been underestimated or not detected. Here, we use patch-clamp, whole-cell current recordings from single neurons acutely dissociated from midbrain nuclei and having features of DA neurons to characterize acetylcholine-induced, inward currents that rapidly activate and desensitize, are mimicked by the alpha7-nAChR-selective agonist, choline, blocked by the alpha7-nAChR-selective antagonists, methyllycaconitine and alpha-bungarotoxin, and are similar to those of heterologously expressed, human alpha7-nAChRs. We also use reverse transcriptase-polymerase chain reaction, in situ hybridization, and immunocytochemical staining to demonstrate nAChR alpha7 subunit gene expression as message and protein in the rat substantia nigra pars compacta and ventral tegmental area. Expression of alpha7 subunit message and of alpha7-nAChR-mediated responses is developmentally regulated, with both being absent in samples taken from rats at postnatal day 7, but later becoming present and increasing over the next 2 weeks. Collectively, this electrophysiological, pharmacological, and molecular evidence indicates that nAChR alpha7 subunits and functional alpha7-nAChRs are expressed somatodendritically by midbrain DA neurons, where they may play important physiological roles and contribute to nicotine reinforcement and dependence.
Animals↗
Stereoselective synthesis of chirally deuterated (S)-D-(6-(2)H(1))glucose.
Chirally deuterated (S)-D-(6-(2)H(1))glucose has been prepared in good overall yield from d-(6,6'-(2)H(2))glucose by a short, five-step synthesis from D-(6,6-(2)H(2))glucose utilizing (R)-(+)-Alpine-Borane [(R)-9-[(6,6-dimethylbicyclo[3.1.1]hept-2-yl)methyl]-9-borabicyclo[3.3.1]nonane]. Suitably protected methyl 2,3,4-tri-O-benzyl-D-(6,6-(2)H(2))glucopyranoside was prepared and the deuterated O-6 primary alcohol was oxidized to an aldehyde by Swern oxidation. Stereoselective reduction with nondeuterated (R)-(+)-Alpine-Borane gave methyl 2,3,4-tri-O-benzyl-(6S)-D-(6-(2)H(1))glucopyranoside, which was deprotected under standard conditions to afford the title compound. The key stereoselective reduction step was achieved in 90% yield. The preparation uses economical, commercially available starting materials and will be useful for elucidating biosynthetic mechanisms.
Carbohydrate Conformation↗
Low dose intravenous minocycline is neuroprotective after middle cerebral artery occlusion-reperfusion in rats.
BACKGROUND: Minocycline, a semi-synthetic tetracycline antibiotic, is an effective neuroprotective agent in animal models of cerebral ischemia when given in high doses intraperitoneally. The aim of this study was to determine if minocycline was effective at reducing infarct size in a Temporary Middle Cerebral Artery Occlusion model (TMCAO) when given at lower intravenous (IV) doses that correspond to human clinical exposure regimens. METHODS: Rats underwent 90 minutes of TMCAO. Minocycline or saline placebo was administered IV starting at 4, 5, or 6 hours post TMCAO. Infarct volume and neurofunctional tests were carried out at 24 hr after TMCAO using 2,3,5-triphenyltetrazolium chloride (TTC) brain staining and Neurological Score evaluation. Pharmacokinetic studies and hemodynamic monitoring were performed on minocycline-treated rats. RESULTS: Minocycline at doses of 3 mg/kg and 10 mg/kg IV was effective at reducing infarct size when administered at 4 hours post TMCAO. At doses of 3 mg/kg, minocycline reduced infarct size by 42% while 10 mg/kg reduced infarct size by 56%. Minocycline at a dose of 10 mg/kg significantly reduced infarct size at 5 hours by 40% and the 3 mg/kg dose significantly reduced infarct size by 34%. With a 6 hour time window there was a non-significant trend in infarct reduction. There was a significant difference in neurological scores favoring minocycline in both the 3 mg/kg and 10 mg/kg doses at 4 hours and at the 10 mg/kg dose at 5 hours. Minocycline did not significantly affect hemodynamic and physiological variables. A 3 mg/kg IV dose of minocycline resulted in serum levels similar to that achieved in humans after a standard 200 mg dose. CONCLUSIONS: The neuroprotective action of minocycline at clinically suitable dosing regimens and at a therapeutic time window of at least 4-5 hours merits consideration of phase I trials in humans in view of developing this drug for treatment of stroke.
Animals↗
The effect of acute stress on LTP and LTD induction in the hippocampal CA1 region of anesthetized rats at three different ages.
Not all experiences are memorized equally well. Especially, some types of stress are unavoidable in daily life and the stress experience can be memorized for life. Previous evidence has showed that synaptic plasticity, such as long-term potentiation (LTP) that may be the major cellular model of the mechanism underlying learning and memory, is influenced by behavioral stress. However, the effect of behavioral stress on age-related synaptic plasticity in vivo was primarily known. Here we found that the LTP induction in the hippocampal CA1 region of anesthetized rats obviously showed inverted-U shape related to ages (4, 10 and 74 weeks old rats), but low-frequency stimulation was unable to induce reliable long-term depression (LTD) in these animals. Furthermore, acute elevated platform (EP) stress enabled reliable LTD significantly and completely blocked LTP induction at these ages. Importantly, LTD after exposure to acute EP stress showed similar magnitude over these ages. The present results that stress enables LTD but impairs LTP induction at these three ages strengthen a view that stress experience-dependent LTD (SLTD) may underlie stress form of aberrant memories.
Age Factors↗
Syntheses, structures, and photoluminescence of a novel class of d10 metal complexes constructed from pyridine-3,4-dicarboxylic acid with different coordination architectures.
Two novel d(10) metal coordination polymers [Zn(PDB)](n)() (1) and [Cd(3)(PDB)(2)(OH)(2)(H(2)O)(2)](n)() (2) (H(2)PDB = pyridine-3,4-dicarboxylic acid) have been synthesized under hydrothermal conditions and characterized by elemental analysis, IR, TG analysis, and single-crystal X-ray diffraction. Crystal data for 1: C(7)H(3)NO(4)Zn, orthorhombic Pna2(1), a = 8.423(17) A, b = 6.574(13) A, c = 12.899(3) A, Z = 4. Crystal data for 2: C(14)H(12)N(2)O(12)Cd(3), monoclinic C2/c, a= 20.130(4) A, b = 6.692(13) A, c = 13.081(3) A, beta = 102.78(3) degrees, Z = 4. Both compounds exhibit novel three-dimensional frameworks. Compound 1 not only possesses a one-dimensional rectangular channel but also contains infinite double-stranded helical chains. Compound 2 has two different types of channels, one being built up from pyridine rings and [CdO(5)N] and [CdO(6)] building units and the other being constructed from pyridine rings and [CdO(5)N] building units. Furthermore, both compounds show strong photoluminescence properties at room temperature.
Journal Article↗
ERECTA is required for protection against heat-stress in the AS1/ AS2 pathway to regulate adaxial-abaxial leaf polarity in Arabidopsis.
In seed plants, formation of the adaxial-abaxial polarity is of primary importance in leaf patterning. Since Arabidopsis thaliana (L.) Heynh. genes ASYMMETRIC LEAVES1 ( AS1) and ASYMMETRIC LEAVES2 ( AS2) are key regulators in specifying adaxial leaf identity, and ERECTA is involved in the AS1/ AS2 pathway for regulating adaxial-abaxial polarity [L. Xu et al. (2003) Development 130:4097-4107], we studied the physiological functions of the ERECTA protein in plant development. We analyzed the effects of different environmental conditions on a special leaf structure in the as1 and as2 mutants. This structure, called the lotus-leaf, reflects a severe loss of adaxial-abaxial polarity in leaves. Higher concentrations of salt or other osmotic substance and lower temperature severely affected plant growth both in the wild type and the mutants, but did not affect lotus-leaf frequency in the as1 and as2 mutants. as1 and as2 mutants exhibited a very low lotus-leaf frequency at 22 degrees C, a temperature that favors Arabidopsis growth. The lotus-leaf frequency rose significantly with an increase in growth temperature, and only in plants that are in the erecta mutation background. These results suggest that ERECTA function is required for reducing plant sensitivity to heat stress during adaxial-abaxial polarity formation in leaves.
Arabidopsis↗
Stress enables synaptic depression in CA1 synapses by acute and chronic morphine: possible mechanisms for corticosterone on opiate addiction.
The hippocampus, being sensitive to stress and glucocorticoids, plays significant roles in certain types of learning and memory. Therefore, the hippocampus is probably involved in the increasing drug use, drug seeking, and relapse caused by stress. We have studied the effect of stress with morphine on synaptic plasticity in the CA1 region of the hippocampus in vivo and on a delayed-escape paradigm of the Morris water maze. Our results reveal that acute stress enables long-term depression (LTD) induction by low-frequency stimulation (LFS) but acute morphine causes synaptic potentiation. Remarkably, exposure to an acute stressor reverses the effect of morphine from synaptic potentiation (approximately 20%) to synaptic depression (approximately 40%), precluding further LTD induction by LFS. The synaptic depression caused by stress with morphine is blocked either by the glucocorticoid receptor antagonist RU38486 or by the NMDA-receptor antagonist D-APV. Chronic morphine attenuates the ability of acute morphine to cause synaptic potentiation, and stress to enable LTD induction, but not the ability of stress in tandem with morphine to cause synaptic depression. Furthermore, corticosterone with morphine during the initial phase of drug use promotes later delayed-escape behavior, as indicated by the morphine-reinforced longer latencies to escape, leading to persistent morphine-seeking after withdrawal. These results suggest that hippocampal synaptic plasticity may play a significant role in the effects of stress or glucocorticoids on opiate addiction.
Animals↗
Designed double layer assembly: a three-dimensional open framework with two types of cavities by connection of infinite two-dimensional bilayer.
A photoluminescent three-dimensional coordination polymer containing two types of cavities is prepared by the covalent linkage of 2D bilayer motif with linear connecting ligand.
Journal Article↗
Optimal delivery of minocycline to the brain: implication for human studies of acute neuroprotection.
Minocycline is currently under development as a neuroprotective agent in many different brain diseases. In more than a dozen experimental investigations in various models of brain injury, high doses of minocycline have been administered intraperitoneally. This report details new concerns with this route of administration and makes a case for intravenous dosing in experimental animals, particularly for acute neuroprotection, to optimize delivery to the brain and facilitate translation to human studies.
Animals↗