During the stress testing session, cortisol responses to two beha

During the stress testing session, cortisol responses to two behavioral selleck compound tasks were assessed. The associations of dispositional optimism with cortisol and subjective appraisal were assessed using hierarchical multiple

regression analysis. Results: The cortisol awakening response, but not the diurnal profile, was negatively associated with optimism independently of age, sex, employment grade, body mass index, smoking status, depressive symptoms, and time of awakening (beta = -0.12, p <= .05). No associations were observed between optimism and stress-induced cortisol changes in the laboratory; however, perceived stress was lower (beta = -0.18, p <= .001), and perception of control was higher (beta = 0.18, p <= .001), in more optimistic participants during the psychophysiological testing session. Conclusions: Dispositional optimism may confer benefits to the individual through attenuated hypothalamic-pituitary-adrenal BTSA1 axis response to waking in everyday life. However, no evidence emerged for an association between optimism and cortisol laboratory stress responses, which suggests that other compensatory mechanisms might

play a role.”
“The t(10;11)(p12;q23) translocation and the t(10;11)(p12;q14) translocation, which encode the MLL (mixed lineage leukemia)-AF10 and CALM (clathrin assembly lymphoid myeloid leukemia)-AF10 fusion oncoproteins, respectively, are two recurrent chromosomal rearrangements

observed in patients with acute myeloid leukemia and acute PAK6 lymphoblastic leukemia. Here, we demonstrate that MLL-AF10 and CALM-AF10-mediated transformation is dependent on the H3K79 methyltransferase Dot1l using genetic and pharmacological approaches in mouse models. Targeted disruption of Dot1l using a conditional knockout mouse model abolished in vitro transformation of murine bone marrow cells and in vivo initiation and maintenance of MLL-AF10 or CALM-AF10 leukemia. The treatment of MLL-AF10 and CALM-AF10 transformed cells with EPZ004777, a specific small-molecule inhibitor of Dot1l, suppressed expression of leukemogenic genes such as Hoxa cluster genes and Meis1, and selectively impaired proliferation of MLL-AF10 and CALM-AF10 transformed cells. Pretreatment with EPZ004777 profoundly decreased the in vivo spleen-colony-forming ability of MLL-AF10 or CALM-AF10 transformed bone marrow cells. These results show that patients with leukemia-bearing chromosomal translocations that involve the AF10 gene may benefit from small-molecule therapeutics that inhibit H3K79 methylation. Leukemia (2013) 27, 813-822;doi:10.1038/leu.2012.327″
“Objective: Psychological stress and sleep disturbances are highly prevalent and are both implicated in the etiology of cardiovascular diseases.

Median followup was 57 weeks (IQR 28, 83)

Results: Th

Median followup was 57 weeks (IQR 28, 83).

Results: The lowest recorded renal temperature during ischemia check details was 14C. Median tumor size was 4.0 cm (IQR 2.7, 6.2). Median estimated blood loss was 150 cc (IQR 100, 275). Median ischemia time was 35 minutes (IQR 26, 41). Doppler echography identified intrarenal arterial

blood flow postoperatively in all cases. The median change in the estimated glomerular filtration rate from preoperatively to postoperative day 2 was 4 ml per minute (IQR -29, 19). Two months postoperative in 20 patients the median change was 3.5 ml per minute (IQR -6, 16.5). At last followup in 31 patients the overall change in the estimated glomerular filtration rate was -0.5 ml per minute (IQR -6, 6). Six complications developed in a total of 5 patients, of which 5 were grade 2 or less. One grade 3 postoperative hemorrhage from an arteriovenous

fistula at the tumor click here resection site was treated with angiography and selective embolization.

Conclusions: Cold intravascular perfusion during laparoscopic partial nephrectomy can achieve renal hypothermia below 15C. It is not associated with an immediate risk of renal vascular injury or thrombosis, as measured by Doppler echography in this series. Early changes in postoperative estimates of renal function appear minimal.”
“Purpose: For the treatment of ureteropelvic junction obstruction laparoscopic dismembered pyeloplasty and open pyeloplasty have similar outcomes. We present our experience with robot assisted laparoscopic dismembered pyeloplasty.

Materials and Methods: We retrospectively reviewed all adult robot assisted laparoscopic dismembered pyeloplasties

performed at our institution between November 2002 and July 2009. Preoperative evaluation included abdominal computerized tomography angiogram to assess for crossing vessels and diuretic renal scan to quantify the degree of obstruction. Followup with diuretic renal scan and a patient pain analog scale was performed 3, 6 and 12 months after surgery. If the study was normal at 12 months, the patient was followed with ultrasound of the kidneys and bladder to Vasopressin Receptor look for ureteral jets. Absent ureteral jets, worsening hydronephrosis or patient complaint of pain necessitated repeat diuretic renogram.

Results: A total of 61 robot assisted laparoscopic dismembered pyeloplasties were performed in 21 men and 40 women. Followup was available for 57 patients with an average +/- SD age of 35 +/- 16 years and average followup of 18 +/- 15 months. Mean operative time was 335 +/- 88 minutes and estimated blood loss was 61 +/- 48 ml. Average hospitalization time was 2 +/- 0.9 days and the average postoperative analgesia requirement was 13 +/- 9.6 mg morphine sulfate equivalents. The overall success rate was 81% based on a normal diuretic renogram and lack of pain using a validated pain scale. There were 3 grade III Clavien complications for a 4.9% major complication rate.

The present study evaluated in SZ patients, whose brain structura

The present study evaluated in SZ patients, whose brain structural data had been obtained with magnetic resonance imaging (MRI), the possible association between structural brain measures, and 32 DNA polymorphisms,located in 30 genes related to neurogenesis and brain development. DNA was extracted from Pritelivir in vitro peripheral blood cells of 25 patients with schizophrenia, genotyping was performed using diverse procedures, and putative associations were evaluated by standard statistical methods (using the software Statistical Package for Social Sciences – SPSS) with a modified Bonferroni adjustment. For reelin (RELN), a protease that guides neurons in the developing brain

and underlies neurotransmission and synaptic plasticity in adults, an association was found for a non-synonymous polymorphism (Va1997Leu) with left and right ventricular enlargement. A putative association was also found between protocadherin 12 (PCDH12), a cell adhesion molecule involved in axonal guidance and

synaptic specificity, and cortical folding (asymmetry coefficient of gyrification index). Although our results are preliminary, due to the small number of individuals analyzed, such an approach could reveal new candidate genes implicated in anomalous neurodevelopment in schizophrenia. (c) 2007 Elsevier Ireland Ltd. All rights reserved.”
“Fractalkine shedding is believed to occur constitutively and following induction via the activity of two membrane-bound enzymes, ADAM-10 and ADAM-17. However, our GSK458 chemical structure previous work suggested that ADAM-17 is not involved in the proteolytic release of fractalkine under TNF treatment of a human adult brain endothelial cell line, hCMEC/D3. The pro-inflammatory cytokine,

TNF, has previously been shown to be expressed in the perivascular cuffs in multiple sclerosis. Here we sought to identify, using siRNAs to silence the expression of ADAM-10 and ADAM-17, whether ADAM-10 is responsible for TNF-induced shedding of fractalkine from the cell membrane in hCMEC/D3. Our findings suggest that ADAM-10, and not ADAM-17, is the major protease involved in fractalkine release under pro-inflammatory conditions in this human adult brain endothelial Methamphetamine cell model. (C) 2012 Elsevier Ireland Ltd. All rights reserved.”
“Background: Vascular access (VA) complications account for a significant number of hospital admissions in dialysis and have substantial costs. A native arteriovenous fistula (AVF) cannot be successfully obtained in all patients. At our center, we established an autogenous brachial-basilic AVF (BBAVF) in the upper arm in patients with a failed forearm fistula or with superficial vessels that were unsuitable for preparing a good site for VA. In most of these patients, we resort to prosthetic materials for creating a functioning VA as the last strategy.

Recently, more proteins have been identified that play important

Recently, more proteins have been identified that play important roles in ODV oral infectivity, including PIF4, PIF5, and SF58, which might work in concert with previously known PIFs to facilitate ODV infection. In order to understand the ODV entry mechanism, the identification of all components of the PIF complex is crucial. Hence, the aim of this study was to identify additional Navitoclax cost components of the PIF complex. Coimmunoprecipitation (CoIP) combined with proteomic analysis was used to identify the components of the Autographa californica multiple nucleopolyhedrovirus

(AcMNPV) PIF complex. PIF4 and P95 (AC83) were identified as components of the PIF complex while PIF5 was not, and this was confirmed with blue native PAGE and a second CoIP. Deletion of the pif4 gene impaired complex formation, but deletion of pif5 did not. Differentially denaturing SDS-PAGE further revealed that PIF4 forms a stable complex with PIF1, PIF2, and PIF3. P95 and P74 are more loosely associated with this complex. Three other proteins, AC5, AC68, and AC108 (homologue of SF58),

were also found by the proteomic analysis to be associated with the PIF complex. Finally the functional significance of the PIF protein interactions is discussed.”
“BACKGROUND: In the past 2 decades, intraoperative GW786034 molecular weight navigation technology has changed preoperative and intraoperative strategies and methodology tremendously.

OBJECTIVE: To report our first experiences with a stereoscopic navigation Org 27569 system based on multimodality-derived, patient-specific 3-dimensional (3-D) information displayed on a stereoscopic monitor and controlled by a virtual user interface.

METHODS: For the planning of each case, a 3-D multimodality model was created on the Dextroscope. The 3-D model was transferred to a console in the operating room that was running Dextroscope-compatible software and included a stereoscopic LCD (liquid crystal display) monitor (DexVue). Surgery was carried out with a standard frameless navigation system (VectorVision, BrainLAB) that was linked to DexVue. Making use of the navigational space coordinates

provided by the VectorVision system during surgery, we coregistered the patient’s 3-D model with the actual patient in the operating room. The 3-D model could then be displayed as seen along the axis of a handheld probe or the microscope view. The DexVue data were viewed with polarizing glasses and operated via a 3-D interface controlled by a cordless mouse containing inertial sensors. The navigational value of DexVue was evaluated postoperatively with a questionnaire. A total of 39 evaluations of 21 procedures were available.

RESULTS: In all 21 cases, the connection of VectorVision with DexVue worked reliably, and consistent spatial concordance of the navigational information was displayed on both systems. The questionnaires showed that in all cases the stereoscopic 3-D data were preferred for navigation.

The solubility

The solubility click here of the recombinant congerin II-tagged BPII increased up to >90% in E coli strain JM109 when coexpressed with the molecular chaperones GroEL, GroES, and trigger factor (Tf). The tag protein was cleaved by digestion with restriction protease, such as alpha-thrombin or Microbacterium liquefaciens protease (MLP), to obtain completely active recombinant BPII. Thus, the congerin-tagged fusion systems containing the cleavage recognition site for alpha-thrombin

or MLP were demonstrated to be highly efficient and useful for producing proteins of desired solubility and activity. (C) 2007 Elsevier Inc. All rights reserved.”
“The remarkable collective action of organisms such as swarming ants, schooling fish and flocking birds has long captivated the attention of artists, naturalists, philosophers and scientists.

Despite a long history of scientific investigation, only now are we beginning to decipher the relationship between individuals AG-120 mw and group-level properties. This interdisciplinary effort is beginning to reveal the underlying principles of collective decision-making in animal groups, demonstrating how social interactions, individual state, environmental modification and processes of informational amplification and decay can all play a part in tuning adaptive response. It is proposed that important commonalities exist with the understanding of neuronal processes and that much could be learned by considering collective animal behavior in the framework of cognitive science.”
“Animal models of drug dependence have described both reductions in brain reward processes and potentiation of stress-like (or anti-reward) mechanisms, including a recruitment of corticotropin-releasing factor (CRF) signaling. Accordingly, chronic exposure to opiates often

leads to the development of mechanical hypersensitivity. We measured paw withdrawal thresholds (PWTs) in male Wistar rats allowed limited (short access group: ShA) or extended (long access group: LgA) access to heroin or cocaine self-administration, or in rats made dependent on ethanol via ethanol vapor exposure (ethanol-dependent group). In heroin self-administering animals, after Carnitine palmitoyltransferase II transition to LgA conditions, thresholds were reduced to around 50% of levels observed at baseline, and were also significantly lower than thresholds measured in animals remaining on the ShA schedule. In contrast, thresholds in animals self-administering cocaine under either ShA (1 h) or LgA (6 h) conditions were unaltered. Similar to heroin LgA rats, ethanol-dependent rats also developed mechanical hypersensitivity after eight weeks of ethanol vapor exposure compared to non-dependent animals. Systemic administration of the CRF1R antagonist MPZP significantly alleviated the hypersensitivity observed in rats dependent on heroin or ethanol.

Secondary functional restorative surgery was performed in 43% of

Secondary functional restorative surgery was performed in 43% of the patients and helped improve individual outcomes, providing a favorable effect on the general functionality of the arm. Among the restorative operations performed, the Steindler procedure, wrist extension restoration, claw hand correction, and free functional muscle flap transfer to the arm and

forearm were the most rewarding.

CONCLUSION: A combination of primary brachial plexus reconstruction and carefully evaluated, selected, and planned function-restorative secondary procedures might offer favorable outcomes in patients with partial or total brachial plexus lesions.”
“Noroviruses (family Caliciviridae) are the RAD001 order major cause of epidemic nonbacterial gastroenteritis in humans, but the mechanism of antibody neutralization is unknown and no structure of an infectious virion has been reported. Murine

norovirus (MNV) is the only norovirus that can be grown in tissue culture, studied in an animal model, and reverse engineered via an infectious clone and to which neutralizing antibodies have been isolated. Presented here are the cryoelectron microscopy structures of an MNV virion and the virion in complex with neutralizing Fab fragments. The most striking differences between MNV and previous calicivirus structures are that the protruding domain is lifted off the shell domain by similar to 16

angstrom and rotated similar to 40 degrees Wnt inhibitor in a clockwise fashion and forms new interactions at the P1 base that create a cagelike structure engulfing the shell domains. Neutralizing Fab fragments cover the outer surface Ribose-5-phosphate isomerase of each copy of the capsid protein P2 domains without causing any apparent conformational changes. These unique features of MNV suggest that at least some caliciviruses undergo a capsid maturation process akin to that observed with other plant and bacterial viruses.”
“OBJECTIVE: The role of stereotactic radiosurgery for the treatment of intracranial benign tumors is well established. There is less experience and more controversy regarding its use for benign tumors of the spine. This study evaluated the clinical efficacy of radiosurgery as part of the treatment paradigm of selected benign tumors of the spine.

METHODS: Seventy-three benign intradural extramedullary spinal tumors were treated with a radiosurgery technique and prospectively evaluated. Patient ages ranged from 18 to 85 years (mean age, 44 yr); the follow-up period was 8 to 71 months (median, 37 mo). Lesion location included 43 cervical, five thoracic, 19 lumbar, and six sacral. Tumor histology included neurofibroma (25 cases), schwannoma (35 cases), and meningioma (13 cases). Twenty-one cases were associated with neurofibromatosis Type 1, and nine patients had neurofibromatosis Type 2.

The hMSC were isolated from healthy human donors and the identity

The hMSC were isolated from healthy human donors and the identity of the undifferentiated hMSC was confirmed by the detection of MSC specific cells surface markers. The hMSC were differentiated along a glial cell lineage using an established cocktail of growth factors including glial growth factor-2. Following differentiation, the hMSC expressed the key Schwann cell (SC) markers at both the transcriptional and translational level. More importantly, we show the functional effect

of hMSC on neurite outgrowth using an in vitro co-culture model system with rat-derived primary sensory neurons. The number of DRG sprouting neurites was significantly enhanced in the presence of differentiated hMSC; neurite length and density (branching) were also increased. These results provide evidence that hMSC can undergo molecular, morphological and functional changes to adopt a SC-like behaviour and, therefore, could be suitable as SC substitutes AZD1152 order for nerve repair in clinical applications. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.”
“Purpose: We analyzed the

diagnostic value of multidetector computerized tomography urography for transitional Cell carcinoma in patients with gross hematuria.

Materials and Methods: All consecutive adult patients with gross hematuria who underwent multidetector computerized tomography urography in a 23 month period were prospectively enrolled. Transitional cell carcinoma an its location on multidetector computerized tomography urography were recorded at a prospective reading with knowledge of the pertinent history and at a retrospective reading while blinded to all information. click here Histological evidence of transitional cell carcinoma served as the gold standard for final diagnosis. Patients who were lost to followup, refused biopsy/surgery for clinically suspicious neoplasms or had negative diagnostic evaluation but a followup of less than I year were excluded from study. We analyzed

the diagnostic value of multidetector computerized tomography urography for transitional cell carcinoma by location with reference this website to final diagnosis.

Results: A total of 139 patients were eligible for study, of whom 24 were excluded from analysis. There was no difference in demographic features between included and excluded patients. Of the 115 included patients 60 had a final diagnosis of a total of 77 transitional cell carcinomas in the renal pelvis, ureter or bladder. Overall sensitivity, specificity and accuracy of multidetector computerized tomography urography for diagnosing transitional cell carcinoma were 0.857, 0.980 and 0.963 at the retrospective reading, and 0.961, 0.988 and 0.984 at the prospective reading, respectively. Multidetector computerized tomography urography had the highest accuracy for diagnosing renal transitional cell carcinoma and the lowest sensitivity for detecting ureteral transitional cell carcinoma.

Our results

show that the molecular layer

Our results

show that the molecular layer CCI-779 in vitro dendritic volume fraction is lower than in the neocortex (10% compared to neocortical 29%). The low total volume fraction of dendrites in the molecular layer is best explained by the majority of the afferents to the dendrites being from the very densely packed parallel fibers, which allows the dendritic fields of individual neurons to be smaller and more compact than in the cerebral cortex. However, the MAP2a,b dendritic volume fraction is even lower (5.2%) than the total volume fraction of dendrites in the molecular layer (10%). Analysis of the material shows that this difference between the two results is due to the unexpected finding that there were few MAP2a,b stained

Purkinje cell spiny dendrites. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Most class I fusion proteins exist as trimers of dimers composed of a receptor binding and a fusion subunit. In their postfusion forms, the three fusion subunits form trimers of hairpins consisting of a central coiled coil (formed by the N-terminal helices), an intervening sequence, and a region containing the C helix (and flanking strands) that runs antiparallel to and packs in the grooves of the N-terminal coiled coil. For filoviruses LY2606368 in vitro and most retroviruses, the intervening sequence includes a “”chain reversal region”" consisting of a short stretch

of hydrophobic residues, a Gly-Gly pair, a CX(6)CC motif, and a bulky hydrophobic residue. Maerz and coworkers (A. L. Maerz, R. J. Center, B. E. Kemp, B. Kobe, and P. Poumbourios, J. Virol. 74: 6614-6621, 2000) proposed a model for this region of human T-cell leukemia virus type 1 (HTLV-1) Env in which expulsion of the final http://www.selleck.co.jp/products/Paclitaxel(Taxol).html bulky hydrophobic residue is important for early conformational changes and specific residues in the chain reversal region are important for forming the final, stable trimer of hairpins. Here, we used mutagenesis and pseudovirus entry assays to test this model for the avian retrovirus avian sarcoma/leukosis virus (ASLV) and the filovirus ebolavirus Zaire. Our results are generally consistent with the model proposed for HTLV-1 Env. In addition, we show with ASLV EnvA that the bulky hydrophobic residue following the CX(6)CC motif is required for the step of prehairpin target membrane insertion, whereas other residues are required for the foldback step of fusion. We further found that a His residue that is unique to the chain reversal region of ASLV EnvA controls the pH at which ASLV entry occurs.”
“Increasing evidence suggests that synaptic zinc, found within the axon terminals of a subset of glutamatergic neurons in the cerebral cortex, is intricately involved in cortical plasticity.

OT may mediate the antidepressant effects of mating behavior (C)

OT may mediate the antidepressant effects of mating behavior. (C) 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.”
“Orexin-A is a neuropeptide involved in the control feeding, arousal or sleep behavior in the hypothalamus. In the present study, the cortex and lateral hypothalamus of rats subjected to middle cerebral artery occlusion (MCAO)-reperfusion brain injury were examined by double immunofluorescence staining. The number of orexin-A-expressing

neurons in the non-ischemic side Selumetinib molecular weight was significantly lower than the ischemic side. Next, orexin-A was administered intracerebroventricularly followed by the induction of MCAO-reperfusion injury. Administration of orexin-A at 0.3 nmol significantly reduced the brain infarct area. The results suggested that orexin-A alters the pathological mechanisms involved in brain ischemia and has a neuroprotective effect. (C) 2010 Elsevier Ireland Ltd and the japan Neuroscience Society. All rights reserved.”
“Background. Due to the increasing longevity of human populations worldwide, there is need of

a useful biomarker for the early detection of cognitive impairment in elderly persons. Both high blood pressure (BP) and inflammatory processes have been reported to be involved in cognitive impairment via cerebrovascular atherosclerosis or neuronal cell damage.

Methods. In this cross-sectional study of 210 ambulatory elderly hypertensive patients without clinically evident dementia (mean age: 74 years; 44% men), we measured 24-hour BP,

circulatory pentraxin selleckchem 3 (PTX3) and high-sensitivity C-reactive protein (hs-CRP) levels, and cognitive function (Mini-Mental State Examination [MMSE]).

Results. A high plasma PTX3 level was observed in lean subjects, especially in those whose current body weight was lower than that measured 5 years earlier, whereas a high hs-CRP level was associated with obesity (all p < .05). Both PTX3 and hs-CRP levels were significantly associated with the MMSE score (r = .248, p<0.001 and r = -.153, p<0.05, respectively); however, in multiple regression analysis, the Aprepitant PTX3 level, but not the hs-CRP level, was inversely associated with the MMSE score independently of patient demographics, glucose and lipid metabolic parameters, 24-hour systolic BP (SBP) level, and the atherosclerotic burden (all p < .05). Moreover, there was a significant interaction between the PTX3 and 24-hour SBP levels in the determinants of MMSE score (p < .05).

Conclusions. A high plasma PTX3 level in elderly hypertensive patients, particularly in those with a high 24-hour BP level, could be a significant predictor of cognitive impairment. A high PTX3 level may be a marker of frailty in elderly hypertensive patients.”
“Mechanisms of plasticity are important to the astounding capacity of the brain to adapt and learn.

Subjects comprised 78 inpatients with major depression and 78 age

Subjects comprised 78 inpatients with major depression and 78 age-, gender- and handedness- matched healthy volunteers, who were investigated with structural magnetic resonance imaging (MRI). The ACC was subdivided into the subgenual, pre-callosal, rostral-anterior and caudal-anterior ACC. No significant differences were observed for ACC volumes between patients and healthy controls. Left ACC volumes showed a significant negative correlation with the number of hospitalizations. These findings suggest that ACC volumes are not altered in patients with major depression,

but that patients with larger ACC have a better clinical outcome than patients with smaller ACC. (C) 2007 Elsevier Ireland Ltd. All rights reserved.”
“The presence selleck screening library of bilateral iliac aneurysms extending to the iliac bifurcations, in conjunction with an abdominal aortic aneurysm, complicates endovascular repair because of the difficulty of preserving one or both hypogastric arteries. Several open techniques have been suggested for hypogastric preservation, but they usually involve some type of anatomic or extra-anatomic bypass. Endovascular Cilengitide datasheet techniques for hypogastric preservation include branch iliac grafts, chimney grafts, and bellbottom

limbs. We report the use of a Viabahn stent graft (W. L. Gore and Associates, Flagstaff, Ariz) within the iliac limb of a Powerlink device (Endologix, Inc, Irvine, Calif) to preserve a hypogastric artery. (J Vase Surg 2011;54:504-6.)”
“Schizophrenia is a devastating chronic psychotic disorder characterized by positive, negative, and cognitive symptoms. Although the positive symptoms are relatively well controlled by current monoamine-based treatments for schizophrenia, these agents provide only modest efficacy against the negative and cognitive symptoms of the disease. Furthermore serious adverse events have been reported during treatment with antipsychotic drugs. Therefore, novel treatment strategies are needed that provide improved efficacy across the Dichloromethane dehalogenase multiple symptom domains of schizophrenia and have improved tolerability/safety profiles. Glutamate is the primary

excitatory neurotransmitter in the mammalian central nervous system (CNS) and plays an important role in physiological and pathological processes of the CNS. Group II metabotropic glutamate receptors (mGlu receptors), in particular, have been shown to modulate glutamatergic activity in brain synapses thought to be involved in the pathophysiology of schizophrenia. In recent years a number of selective mGlu2/3 receptor agonists and mGlu2 positive allosteric modulators have been disclosed with demonstrated efficacy in multiple animal models for schizophrenia. Consistent with predictions from pre-clinical animal studies, LY2140023 monohydrate, an mGlu2/3 receptor agonist prodrug, recently demonstrated evidence for antipsychotic activity in phase II proof of concept study.