NMR Evidence for Charge Inhomogeneity in Stripe Ordered La_{1.8-x}Eu_{0.2}Sr_{x}CuO_4

We report ^{17}O Nuclear Magnetic Resonance (NMR) results in the stripe ordered La_{1.8-x}Eu_{0.2}Sr_{x}CuO_4 system. Below a temperature T_q ~ 80K, the local electric field gradient (EFG) and the absolute intensity of the NMR signal of the planar O site exhibit a dramatic decrease. We interpret these results as microscopic evidence for a spatially inhomogeneous charge distribution, where the NMR signal from O sites in the domain walls of the spin density modulation are wiped out due to large hyperfine fields, and the remaining signal arises from the intervening Mott insulating regions.Comment: 4 pages, to appear in Phys. Rev. Let

Disorder-induced Spin Gap in the Zigzag Spin-1/2 Chain Cuprate Sr_{0.9}Ca_{0.1}CuO_2

We report a comparative study of 63Cu Nuclear Magnetic Resonance spin lattice relaxation rates, T_1^{-1}, on undoped SrCuO_2 and Ca doped Sr_{0.9}Ca_{0.1}CuO_2 spin chain compounds. A temperature independent T_1^{-1} is observed for SrCuO_2 as expected for an S=1/2 Heisenberg chain. Surprisingly, we observe an exponential decrease of T_1^{-1} for T < 90,K in the Ca-doped sample evidencing the opening of a spin gap. The data analysis within the J_1-J_2 Heisenberg model employing density-matrix renormalization group calculations suggests an impurity driven small alternation of the J_2-exchange coupling as a possible cause of the spin gap.Comment: 4 pages, 4 figure

Orexin 2 receptor regulation of the hypothalamic–pituitary–adrenal (HPA) response to acute and repeated stress

Orexins are hypothalamic neuropeptides that have a documented role in mediating the acute stress response. However, their role in habituation to repeated stress, and the role of orexin receptors (OX1R and OX2R) in the stress response, has yet to be defined. Orexin neuronal activation and levels in the cerebrospinal fluid were found to be stimulated with acute restraint, but were significantly reduced by day five of repeated restraint. As certain disease states such as panic disorder are associated with increased central orexin levels and failure to habituate to repeated stress, the effect of activating orexin signaling via Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) on the hypothalamic-pituitary-adrenal (HPA) response was evaluated after repeated restraint. While vehicle-treated rats displayed habituation of Adrenocorticotropic Hormone (ACTH) from day 1 to day 5 of restraint, stimulating orexins did not further increase ACTH beyond vehicle levels for either acute or repeated restraint. We delineated the roles of orexin receptors in acute and repeated stress by using a selective OX2R antagonist (MK-1064). Pretreatment with MK-1064 reduced day 1 ACTH levels, but did not allow further habituation on day 5 compared with vehicle-treated rats, indicating that endogenous OX2R activity plays a role in acute stress, but not in habituation to repeated stress. However, in restrained rats with further stimulated orexins by DREADDs, MK-1064 decreased ACTH levels on day 5. Collectively, these results indicate that the OX2R plays a role in acute stress, and can prevent habituation to repeated stress under conditions of high orexin release

Orexin 2 receptor regulation of the hypothalamic–pituitary–adrenal (HPA) response to acute and repeated stress

Orexins are hypothalamic neuropeptides that have a documented role in mediating the acute stress response. However, their role in habituation to repeated stress, and the role of orexin receptors (OX1R and OX2R) in the stress response, has yet to be defined. Orexin neuronal activation and levels in the cerebrospinal fluid were found to be stimulated with acute restraint, but were significantly reduced by day five of repeated restraint. As certain disease states such as panic disorder are associated with increased central orexin levels and failure to habituate to repeated stress, the effect of activating orexin signaling via Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) on the hypothalamic-pituitary-adrenal (HPA) response was evaluated after repeated restraint. While vehicle-treated rats displayed habituation of Adrenocorticotropic Hormone (ACTH) from day 1 to day 5 of restraint, stimulating orexins did not further increase ACTH beyond vehicle levels for either acute or repeated restraint. We delineated the roles of orexin receptors in acute and repeated stress by using a selective OX2R antagonist (MK-1064). Pretreatment with MK-1064 reduced day 1 ACTH levels, but did not allow further habituation on day 5 compared with vehicle-treated rats, indicating that endogenous OX2R activity plays a role in acute stress, but not in habituation to repeated stress. However, in restrained rats with further stimulated orexins by DREADDs, MK-1064 decreased ACTH levels on day 5. Collectively, these results indicate that the OX2R plays a role in acute stress, and can prevent habituation to repeated stress under conditions of high orexin release

A case of recurrent epilepsy-associated rosette-forming glioneuronal tumor with anaplastic transformation in the absence of therapy.

Rosette-forming glioneuronal tumor (RGNT) most commonly occurs adjacent to the fourth ventricle and therefore rarely presents with epilepsy. Recent reports describe RGNT occurrence in other anatomical locations with considerable morphologic and genetic overlap with the epilepsy-associated dysembryoplastic neuroepithelial tumor (DNET). Examples of RGNT or DNET with anaplastic change are rare, and typically occur in the setting of radiation treatment. We present the case of a 5-year-old girl with seizures, who underwent near total resection of a cystic temporal lobe lesion. Pathology showed morphologic and immunohistochemical features of RGNT, albeit with focally overlapping DNET-like patterns. Resections of residual or recurrent tumor were performed 1 year and 5 years after the initial resection, but no adjuvant radiation or chemotherapy was given. Ten years after the initial resection, surveillance imaging identified new and enhancing nodules, leading to another gross total resection. This specimen showed areas similar to the original tumor, but also high-grade foci with oligodendroglial morphology, increased cellularity, palisading necrosis, microvascular proliferation, and up to 13 mitotic figures per 10 high power fields. Ancillary studies the status by sequencing showed wild-type of the isocitrate dehydrogenase 1 (IDH1), IDH2, and human histone 3.3 (H3F3A) genes, and BRAF studies were negative for mutation or rearrangement. Fluorescence in situ hybridization (FISH) showed codeletion of 1p and 19q limited to the high-grade regions. By immunohistochemistry there was loss of nuclear alpha-thalassemia mental retardation syndrome, X-linked (ATRX) expression only in the high-grade region. Next-generation sequencing showed an fibroblast growth factor receptor receptor 1 (FGFR1) kinase domain internal tandem duplication in three resection specimens. ATRX mutation in the high-grade tumor was confirmed by sequencing which showed a frameshift mutation (p.R1427fs), while the apparent 1p/19q-codeletion by FISH was due to loss of chromosome arm 1p and only partial loss of 19q. Exceptional features of this case include the temporal lobe location, 1p/19q loss by FISH without true whole-arm codeletion, and anaplastic transformation associated with ATRX mutation without radiation or chemotherapy

Orexin signaling during social defeat stress influences subsequent social interaction behaviour and recognition memory

Orexins are neuropeptides synthesized in the lateral hypothalamus that influence arousal, feeding, reward pathways, and the response to stress. However, the role of orexins in repeated stress is not fully characterized. Here, we examined how orexins and their receptors contribute to the coping response during repeated social defeat and subsequent anxiety-like and memory-related behaviors. Specifically, we used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to stimulate orexins prior to each of five consecutive days of social defeat stress in adult male rats. Additionally, we determined the role of the orexin 2 receptor in these behaviors by using a selective orexin 2 receptor antagonist (MK-1064) administered prior to each social defeat. Following the 5 day social defeat conditioning period, rats were evaluated in social interaction and novel object recognition paradigms to assess anxiety-like behavior and recognition memory, respectively. Activation of orexin neurons by DREADDs prior to each social defeat decreased the average latency to become defeated across 5 days, indicative of a passive coping strategy that we have previously linked to a stress vulnerable phenotype. Moreover, stimulation of orexin signaling during defeat conditioning decreased subsequent social interaction and performance in the novel object recognition test indicating increased subsequent anxiety-like behavior and reduced working memory. Blocking the orexin 2 receptor during repeated defeat did not alter these effects. Together, our results suggest that orexin neuron activation produces a passive coping phenotype during social defeat leading to subsequent anxiety-like behaviors and memory deficits

NMR evidence for inhomogeneous glassy behavior driven by nematic fluctuations in iron arsenide superconductors

We present $^{75}$As nuclear magnetic resonance spin-lattice and spin-spin relaxation rate data in Ba(Fe$_{1-x}$Co$_x$)$_2$As$_2$ and Ba(Fe$_{1-x}$Cu$_x$)$_2$As$_2$ as a function of temperature, doping and magnetic field. The relaxation curves exhibit a broad distribution of relaxation rates, consistent with inhomogeneous glassy behavior up to 100 K. The doping and temperature response of the width of the dynamical heterogeneity is similar to that of the nematic susceptibility measured by elastoresistance measurements. We argue that quenched random fields which couple to the nematic order give rise to a nematic glass that is reflected in the spin dynamics.Comment: Accepted to Physical Review