Crystallization and preliminary X-ray crystallographic analysis of SEDL

SEDL (known also as sedlin) is a 140 amino-acid protein with a putative role in endoplasmic reticulum-to-Golgi transport. Several missense mutations and deletion mutations in the SEDL gene, which result in protein truncation by frame shift, are responsible for spondyloepiphyseal dysplasia tarda, a progressive skeletal disorder. The protein is identical to MIP-2A, which was shown to interact physically with c-myc promotor-binding protein 1 (MBP-1) and relieve the regulatory role of MBP-1 as a general transcription repressor. In order to gain insights into the function of SEDL by structural analysis, the protein was overexpressed and crystallized as a first step. SEDL was overexpressed in Escherichia coli and crystallized using the hanging-drop vapour-diffusion method at 298 K. The crystals belong to the orthorhombic space group C2221, with unit-cell parameters a = 46.69, b = 101.30, c = 66.15 A. The unit cell is likely to contain one molecule of SEDL, with a crystal volume per protein mass (VM) of 2.36 A3 Da-1 and a solvent content of about 47.9% by volume. A native data set to 2.8 A resolution was obtained from a flash-cooled crystal using synchrotron radiation.open1

Giant Magnetic Fluctuations at the Critical Endpoint in Insulating HoMnO3

Although abundant research has focused recently on the quantum criticality of itinerant magnets, critical phenomena of insulating magnets in the vicinity of critical endpoints (CEP's) have rarely been revealed. Here we observe an emergent CEP at 2.05 T and 2.2 K with a suppressed thermal conductivity and concomitant strong critical fluctuations evident via a divergent magnetic susceptibility (e.g., ????????(2.05 T,2.2 K)/????????(3 T,2.2 K)≈23,500%, comparable to the critical opalescence in water) in the hexagonal insulating antiferromagnet HoMnO3. © 2013 American Physical Society.open1

NF-κB mediated enhancement of potassium currents by the chemokine CXCL1/growth related oncogene in small diameter rat sensory neurons

<p>Abstract</p> <p>Background</p> <p>Inflammatory processes play important roles in both neuropathic and inflammatory pain states, but the effects of inflammation <it>per se </it>within the sensory ganglia are not well understood. The cytokine growth-related oncogene (GRO/KC; CXCL1) shows strong, rapid upregulation in dorsal root ganglion (DRG) in both nerve injury and inflammatory pain models. We examined the direct effects of GRO/KC on small diameter DRG neurons, which are predominantly nociceptive. Whole cell voltage clamp technique was used to measure voltage-activated potassium (K) currents in acutely cultured adult rat small diameter sensory neurons. Fluorescently labeled isolectin B4 (IB4) was used to classify cells as IB4-positive or IB4-negative.</p> <p>Results</p> <p>In IB4-negative neurons, voltage-activated K current densities of both transient and sustained components were increased after overnight incubation with GRO/KC (1.5 nM), without marked changes in voltage dependence or kinetics. The average values for the slow and fast decay time constants at 20 mV were unchanged by GRO/KC. The amplitude of the fast inactivating component increased significantly with no large shifts in the voltage dependence of inactivation. The increase in K currents was completely blocked by co-incubation with protein synthesis inhibitor cycloheximide (CHX) or NF-κB inhibitors pyrrolidine dithiocarbamate (PDTC) or quinazoline (6-Amino-4-(4-phenoxypheny lethylamino;QNZ). In contrast, the voltage-activated K current of IB4-positive neurons was unchanged by GRO/KC. GRO/KC incubation caused no significant changes in the expression level of eight selected voltage-gated K channel genes in quantitative PCR analysis.</p> <p>Conclusion</p> <p>The results suggest that GRO/KC has important effects in inflammatory processes via its direct actions on sensory neurons, and that activation of NF-κB is involved in the GRO/KC-induced enhancement of K currents.</p

Differential regulation of immune responses and macrophage/neuron interactions in the dorsal root ganglion in young and adult rats following nerve injury

Background: Neuropathic pain is an apparently spontaneous experience triggered by abnormal physiology of the peripheral or central nervous system, which evolves with time. Neuropathic pain arising from peripheral nerve injury is characterized by a combination of spontaneous pain, hyperalgesia and allodynia. There is no evidence of this type of pain in human infants or rat pups; brachial plexus avulsion, which causes intense neuropathic pain in adults, is not painful when the injury is sustained at birth. Since infants are capable of nociception from before birth and display both acute and chronic inflammatory pain behaviour from an early neonatal age, it appears that the mechanisms underlying neuropathic pain are differentially regulated over a prolonged postnatal period.Results: We have performed a microarray analysis of the rat L4/L5 dorsal root ganglia (DRG), 7 days post spared nerve injury, a model of neuropathic pain. Genes that are regulated in adult rats displaying neuropathic behaviour were compared to those regulated in young rats (10 days old) that did not show the same neuropathic behaviour. The results show a set of genes, differentially regulated in the adult DRG, that are principally involved in immune system modulation. A functional consequence of this different immune response to injury is that resident macrophages cluster around the large A sensory neuron bodies in the adult DRG seven days post injury, whereas the macrophages in young DRG remain scattered evenly throughout the ganglion, as in controls.Conclusions: The results show, for the first time, a major difference in the neuroimmune response to nerve injury in the dorsal root ganglion of young and adult rats. Differential analysis reveals a new set of immune related genes in the ganglia, that are differentially regulated in adult neuropathic pain, and that are consistent with the selective activation of macrophages around adult, but not young large A sensory neurons post injury. These differences may contribute to the reduced incidence of neuropathic pain in infants

Glial TNFα in the spinal cord regulates neuropathic pain induced by HIV gp120 application in rats

<p>Abstract</p> <p>Background</p> <p>HIV-associated sensory neuropathy (HIV-SN) is one of the most common forms of peripheral neuropathy, affecting about 30% of people with acquired immune deficiency syndrome (AIDS). The symptoms of HIV-SN are dominated by neuropathic pain. Glia activation in the spinal cord has become an attractive target for attenuating chronic pain. This study will investigate the role of spinal TNFα released from glia in HIV-related neuropathic pain.</p> <p>Results</p> <p>Peripheral gp120 application into the rat sciatic nerve induced mechanical allodynia for more than 7 weeks, and upregulated the expression of spinal TNFα in the mRNA and the protein levels at 2 weeks after gp120 application. Spinal TNFα was colocalized with GFAP (a marker of astrocytes) and Iba1 (a marker of microglia) in immunostaining, suggesting that glia produce TNFα in the spinal cord in this model. Peripheral gp120 application also increased TNFα in the L4/5 DRG. Furthermore, intrathecal administration of TNFα siRNA or soluble TNF receptor reduced gp120 application-induced mechanical allodynia.</p> <p>Conclusions</p> <p>Our results indicate that TNFα in the spinal cord and the DRG are involved in neuropathic pain, following the peripheral HIV gp120 application, and that blockade of the glial product TNFα reverses neuropathic pain induced by HIV gp120 application.</p

Effect of cyclosporine on hepatic cytosolic estrogen and androgen receptor levels before and after partial hepatectomy

Estrogen and androgen receptors within the liver have been reported to modulate the hepatic regenerative response to partial hepatectomy. Moreover, cyclosporine has several untoward effects that might occur as a consequence of alterations in sex hormone activity. To evaluate these questions the following experiments were performed. Estrogen and androgen receptors in cytosol were quantitated in livers of rats treated with cyclosporine or olive oil vehicle before and after partial hepatectomy or a sham operation. Ornithine decarboxylase activity and thymidine kinase activity were assessed as indices of hepatic regeneration. Preoperative levels of estrogen receptor activity in the hepatic cytosol were significantly greater in rats treated with cyclosporine as compared to vehicle treated controls (P<0.01). In contrast, preoperative levels of androgen receptor activity in the cyclosporine-treated and vehicle-treated animals were similar. Following partial hepatectomy, a reduction in the activity of both sex hormone receptors in the hepatic cytosol was observed and was compatible with results described previously in normal animals. Unexpectedly the preoperative levels of ornithine decarboxylase (P<0.01) and thymidine kinase activity (P<0.01) were significantly greater in the rats treated with cyclosporine as compared to the vehicle treated controls. As expected, ornithine decarboxylase activity (at 6 hr) and thymidine kinase activity (at 24 hr) rose and peaked in response to a partial hepatectomy but were significantly greater (P<0.05) in the rats treated with cyclosporine as compared to the vehicle. These results show that cyclosporine treatment causes an increase in the hepatic content of estrogen receptor activity that is associated with an enhanced potential for a regenerative response. These effects of cyclosporine treatment on the sex hormone receptor levels in liver may explain the mechanisms responsible for some of the untoward effects of treatment with this agent. © 1990 Plenum Publishing Corporation

An Integrated-Photonics Optical-Frequency Synthesizer

Integrated-photonics microchips now enable a range of advanced functionalities for high-coherence applications such as data transmission, highly optimized physical sensors, and harnessing quantum states, but with cost, efficiency, and portability much beyond tabletop experiments. Through high-volume semiconductor processing built around advanced materials there exists an opportunity for integrated devices to impact applications cutting across disciplines of basic science and technology. Here we show how to synthesize the absolute frequency of a lightwave signal, using integrated photonics to implement lasers, system interconnects, and nonlinear frequency comb generation. The laser frequency output of our synthesizer is programmed by a microwave clock across 4 THz near 1550 nm with 1 Hz resolution and traceability to the SI second. This is accomplished with a heterogeneously integrated III/V-Si tunable laser, which is guided by dual dissipative-Kerr-soliton frequency combs fabricated on silicon chips. Through out-of-loop measurements of the phase-coherent, microwave-to-optical link, we verify that the fractional-frequency instability of the integrated photonics synthesizer matches the $7.0*10^{-13}$ reference-clock instability for a 1 second acquisition, and constrain any synthesis error to $7.7*10^{-15}$ while stepping the synthesizer across the telecommunication C band. Any application of an optical frequency source would be enabled by the precision optical synthesis presented here. Building on the ubiquitous capability in the microwave domain, our results demonstrate a first path to synthesis with integrated photonics, leveraging low-cost, low-power, and compact features that will be critical for its widespread use.Comment: 10 pages, 6 figure

Analysis of different characteristics of smile

Introduction: Analysis of smile is imperative in the diagnosis and treatment planning phases of aesthetic dentistry.Aim: To evaluate the components of smile among students of a dental institution.Methods: Frontal view digital photographs with posed smile of 157 dental students were assessed using Adobe Photoshop7.0. Smile characteristics evaluated included; smile line, smile arc, smile design, upper lip curvature, labiodental relationship and number of teeth displayed. Data were analyzed using SPSS version 23.0. Pearson chi-square test was used to determine the gender based differences for various parameters.Results: Average smile line (43.3%), consonant smile arcs (45.2%), cuspid smiles (45.9%), upward lip curvature (43.9%), maxillary anterior teeth not covered by lower lip (60.5%) and teeth displayed up to first premolars (35.7%). Gender based differences were not statistically significant except for smile arc (p value = 0.02) and number of teeth displayed (p value \u3c 0.001). There was a significant relationship between lip curvature and smile pattern (p value \u3c 0.001) and lip curvature and smile arc (p value = 0.01) revealing that upward lip curvature was associated with commissure type smiles and consonant smile arcs.Conclusions: The smile characteristics should be considered before beginning the aesthetic treatment of the patient to obtain adequate results in oral rehabilitation

Caffeine-induced synaptic potentiation in hippocampal CA2 neurons

Caffeine enhances cognition, but even high non-physiological doses have modest effects on synapses. A 1 adenosine receptors (A 1 Rs) are antagonized by caffeine and are most highly enriched in hippocampal CA2, which has not been studied in this context. We found that physiological doses of caffeine in vivo or A 1 R antagonists in vitro induced robust, long-lasting potentiation of synaptic transmission in rat CA2 without affecting other regions of the hippocampus