Prior stress promotes the generalization of contextual fear memories: Involvement of the gabaergic signaling within the basolateral amygdala complex.

Fear generalization occurs when a response, previously acquired with a threatening stimulus, is transferred to a similar one. However, it could be maladaptive when stimuli that do not represent a real threat are appraised as dangerous, which is a hallmark of several anxiety disorders. Stress exposure is a major risk factor for the occurrence of anxiety disorders and it is well established that it influences different phases of fear memory; nevertheless, its impact on the generalization of contextual fear memories has been less studied. In the present work, we have characterized the impact of acute restraint stress prior to contextual fear conditioning on the generalization of this fear memory, and the role of the GABAergic signaling within the basolateral amygdala complex (BLA) on the stress modulatory effects. We have found that a single stress exposure promoted the generalization of this memory trace to a different context that was well discriminated in unstressed conditioned animals. Moreover, this effect was dependent on the formation of a contextual associative memory and on the testing order (i.e., conditioning context first vs generalization context first). Furthermore, we observed that increasing GABA-A signaling by intra-BLA midazolam administration prior to the stressful session exposure prevented the generalization of fear memory, whereas intra-BLA administration of the GABA-A antagonist (Bicuculline), prior to fear conditioning, induced the generalization of fear memory in unstressed rats. We concluded that stress exposure, prior to contextual fear conditioning, promotes the generalization of fear memory and that the GABAergic transmission within the BLA has a critical role in this phenomenon.

PD-1 blockade: a therapeutic option for treatment of metastatic Merkel cell carcinoma.

The immune system is extremely important in the development and progression of Merkel cell carcinoma (MCC). Immune checkpoint blockade has recently been shown to enable efficacious treatment of a variety of tumours. We report the use of an anti-programmed death receptor 1 (PD-1) antibody for treatment of a patient with metastatic MCC. An 80-year-old patient with metastatic MCC received off-label treatment with the anti-PD-1 antibody pembrolizumab after the disease had progressed during therapy with oral etoposide. A positron emission tomography (PET) computed tomography scan performed after three cycles of pembrolizumab revealed responses to therapy with reduced size of the adrenal gland metastases and less PET activity in the adrenal gland and lymph node metastases. Treatment was resumed owing to disease progression after a treatment-free interval of > 4 months. During subsequent months of treatment, the size of the metastases stabilized and uptake of nuclide by all tumour sites once again decreased. These results reveal the potential efficacy of an anti-PD-1 antibody for treatment of metastatic MCC. Thus, they contribute to currently limited data on the use of anti-PD-1 antibodies for the treatment of MCC. Moreover, this is the first report of successful resumption of treatment of metastatic MCC with an anti-PD-1 antibody. Results from ongoing trials will contribute to determination of the relevance of PD-1 blockade in metastatic MCC.

Development of a Greenhouse Screening Method for Adult Plant Response in Wheat to Stem Rust.

Screening for adult plant resistance in wheat to stem rust, caused by Puccinia graminis f. sp. tritici, is generally conducted in field plots. Although such evaluations are successful if managed properly, field ratings are time consuming, expensive, weather dependent, and open to inoculum of unwanted races or other confounding diseases. The objective of this study was to develop a dependable system of screening the response of adult plants to stem rust under greenhouse conditions. A comparison of inoculation methods and incubation environments showed that plants inoculated with urediniospores suspended in water, followed by a 24 h dew period in a plastic chamber constructed in a greenhouse, gave the most consistent results. Measurements of response type, stem rust severity, and frequency in follow-up experiments indicated that the most reliable infection was obtained when plants sprayed with 1.25 mg urediniospores per ml water were incubated in the plastic chamber. Using the optimized protocol, a Kariega × Avocet S doubled haploid population was inoculated with two P. graminis f. sp. tritici races. Depending on the race, composite interval mapping showed flag leaf infection type to be significantly influenced by regions on chromosomes 6A, 6D, and 7D. Stem rust severity and reaction type mapped to chromosomes 6D and/or 6A. The Lr34/Yr18/Sr57 gene derived from Kariega on chromosome 7D affected the rust response on flag leaves but not on stems of greenhouse-grown plants. This study showed that phenotyping and genetic analysis of especially major effect stem rust resistance in adult wheat plants is possible and reproducible under controlled conditions in a greenhouse.

MicroRNA-206 functions as a pleiotropic modulator of cell proliferation, invasion and lymphangiogenesis in pancreatic adenocarcinoma by targeting ANXA2 and KRAS genes.

Recent advances in cancer biology have emerged important roles for microRNAs (miRNAs) in regulating tumor responses. However, their function in mediating intercellular communication within the tumor microenvironment is thus far poorly explored. Here, we found miR-206 to be abrogated in human pancreatic ductal adenocarcinoma (PDAC) specimens and cell lines. We show that miR-206 directly targets the oncogenes KRAS and annexin a2 (ANXA2), thereby acting as tumor suppressor in PDAC cells by blocking cell cycle progression, cell proliferation, migration and invasion. Importantly, we identified miR-206 as a negative regulator of oncogenic KRAS-induced nuclear factor-κB transcriptional activity, resulting in a concomitant reduction of the expression and secretion of pro-angiogenic and pro-inflammatory factors including the cytokine interleukin-8, the chemokines (C-X-C motif) ligand 1 and (C-C motif) ligand 2, and the granulocyte macrophage colony-stimulating factor. We further show that miR-206 abrogates the expression and secretion of the potent pro-lymphangiogenic factor vascular endothelial growth factor C in pancreatic cancer cells through an NF-κB-independent mechanism. By using in vitro and in vivo approaches, we reveal that re-expression of miR-206 in PDAC cells is sufficient to inhibit tumor blood and lymphatic vessel formation, thus leading to a significant delay of tumor growth and progression. Taken together, our study sheds light onto the role of miR-206 as a pleiotropic modulator of different hallmarks of cancer, and as such raising the intriguing possibility that miR-206 may be an attractive candidate for miRNA-based anticancer therapies.

Loss-induced suppression and revival of lasing.

Controlling and reversing the effects of loss are major challenges in optical systems. For lasers, losses need to be overcome by a sufficient amount of gain to reach the lasing threshold. In this work, we show how to turn losses into gain by steering the parameters of a system to the vicinity of an exceptional point (EP), which occurs when the eigenvalues and the corresponding eigenstates of a system coalesce. In our system of coupled microresonators, EPs are manifested as the loss-induced suppression and revival of lasing. Below a critical value, adding loss annihilates an existing Raman laser. Beyond this critical threshold, lasing recovers despite the increasing loss, in stark contrast to what would be expected from conventional laser theory. Our results exemplify the counterintuitive features of EPs and present an innovative method for reversing the effect of loss.

Efficacy of different carrier gases for barrier discharge plasma generation compared to chlorhexidine on the survival of Pseudomonas aeruginosa embedded in biofilm in vitro.

Because of its antimicrobial properties, nonthermal plasma could serve as an alternative to chemical antisepsis in wound treatment. Therefore, this study investigated the inactivation of biofilm-embedded Pseudomonas aeruginosa SG81 by a surface barrier-discharged (SBD) plasma for 30, 60, 150 and 300 s. In order to optimize the efficacy of the plasma, different carrier gases (argon, argon admixed with 1% oxygen, and argon with increased humidity up to approx. 80%) were tested and compared against 0.1% chlorhexidine digluconate (CHG) exposure for 600 s. The antimicrobial efficacy was determined by calculating the difference between the numbers of colony-forming units (CFU) of treated and untreated biofilms. Living bacteria were distinguished from dead by fluorescent staining and confocal laser scanning microscopy. Both SBD plasmas and CHG showed significant antimicrobial effects compared to the untreated control. However, plasma treatment led to a higher antimicrobial reduction (argon plasma 4.9 log10 CFU/cm(2), argon with admixed oxygen 3 log10 CFU/cm(2), and with increased gas humidity 2.7 log10 CFU/cm(2) after 300 s) compared to CHG. In conclusion, SBD plasma is suitable as an alternative to CHG for inactivation of Pseudomonas aeruginosa embedded in biofilm. Further development of SBD plasma sources and research on the role of carrier gases and humidity may allow their clinical application for wound management in the future.

Negative allosteric modulation of metabotropic glutamate receptor 5 results in broad spectrum activity relevant to treatment resistant depression.

Evidence suggests that 30-50% of patients suffering from major depressive disorder (MDD) are classified as suffering from treatment resistant depression (TRD) as they have an inadequate response to standard antidepressants. A key feature of this patient population is the increased incidence of co-morbid symptoms like anxiety and pain. Recognizing that current standards of care are largely focused on monoaminergic mechanisms of action (MOAs), innovative approaches to drug discovery for TRD are targeting glutamate hyperfunction. Here we describe the in vitro and in vivo profile of GRN-529, a novel negative allosteric modulator (NAM) of metabotropic glutamate receptor 5 (mGluR5). In cell based pharmacology assays, GRN-529 is a high affinity (Ki 5.4 nM), potent (IC50 3.1 nM) and selective (>1000-fold selective vs mGluR1) mGluR5 NAM. Acute administration of GRN-529 (0.1-30 mg/kg p.o.) had dose-dependent efficacy across a therapeutically relevant battery of animal models, comprising depression (decreased immobility time in tail suspension and forced swim tests) and 2 of the co-morbid symptoms overrepresented in TRD, namely anxiety (attenuation of stress-induced hyperthermia, and increased punished crossings in the four plate test) and pain (reversal of hyperalgesia due to sciatic nerve ligation or inflammation). The potential side effect liability of GRN-529 was also assessed using preclinical models: GRN-529 had no effect on rat sexual behavior or motor co-ordination (rotarod), however it impaired cognition in mice (social odor recognition). Efficacy and side effects of GRN-529 were compared to standard of care agents (antidepressant, anxiolytic or analgesics) and the tool mGluR5 NAM, MTEP. To assess the relationship between target occupancy and efficacy, ex vivo receptor occupancy was measured in parallel with efficacy testing. This revealed a strong correlation between target engagement, exposure and efficacy across behavioral endpoints, which supports the potential translational value of PET imaging to dose selection in patients. Collectively this broad spectrum profile of efficacy of GRN-529 supports our hypothesis that negative allosteric modulation of mGluR5 could represent an innovative therapeutic approach to the treatment of TRD. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.

Clinical use of the antiseptic polihexanide for genital tract infections.

BACKGROUND: In clinical practice, treatment of genital tract infections is based on administration of either antibiotics or antiseptics. While antibiotics may be applied systemically or topically, antiseptics may be applied only topically. In case of bacterial vaginosis (BV), antibiotic therapy may often be limited and side effects due to systemic administration may develop. Polihexanide (PHMB) is a promising option for the topical treatment of genital tract infections, in particular BV and vaginitis. METHOD: A systematic search for publications on the use of PHMB for the treatment of genital infections in two electronic databases was performed. Titles, abstracts and citations were imported into a reference database. Duplicates were removed and two reviewers assessed each identified publication separately. RESULTS: Among a total of 204 references, 3 prospective randomized trials were identified. Two trials treated BV infections with PHMB in comparison to clindamycin as antibiotic standard therapy with no significant differences either in safety or in efficacy. The third controlled trial investigated the clinical efficacy of PHMB compared to placebo in the treatment of human papilloma virus. Patients treated with PHMB daily for up to 16-weeks showed significantly higher (52%) clearance of genital warts as compared to patients treated with placebo (4%). CONCLUSION: PHMB may be a clinically effective alternative for the treatment of BV and human papilloma virus. Although PHMB-based antiseptics are available since the late 90s, controlled trials to investigate its clinical potential for antiseptic treatment are scant. Clinical use of antiseptics for the treatment of infectious diseases should be explored and supported further.

Identification of adult plant resistance to stripe rust in the wheat cultivar Cappelle-Desprez.

Following the appearance of stripe rust in South Africa in 1996, efforts have been made to identify new sources of durable resistance. The French cultivar Cappelle-Desprez has long been considered a source of durable, adult plant resistance (APR) to stripe rust. As Cappelle-Desprez contains the seedling resistance genes Yr3a and Yr4a, wheat lines were developed from which Yr3a and Yr4a had been removed, while selecting for Cappelle-Desprez derived APR effective against South African pathotypes of the stripe rust fungus, Puccinia striiformis f. sp. tritici. Line Yr16DH70, adapted to South African wheat growing conditions, was selected and crossed to the stripe rust susceptible cultivar Palmiet to develop a segregating recombinant inbred line mapping population. A major effect QTL, QYr.ufs-2A was identified on the short arm of chromosome 2A derived from Cappelle-Desprez, along with three QTL of smaller effect, QYr.ufs-2D, QYr.ufs-5B and QYr.ufs-6D. QYr.ufs-2D was located within a region on the short arm of chromosome 2D believed to be the location of the stripe rust resistance gene Yr16. An additional minor effect QTL, QYr.ufs-4B, was identified in the cv. Palmiet. An examination of individual RILs carrying single or combinations of each QTL indicated significant resistance effects when QYr.ufs-2A was combined with the three minor QTL from Cappelle-Desprez, and between QYr.ufs-2D and QYr.ufs-5B.

Strong EGFR signaling in cell line models of ERBB2-amplified breast cancer attenuates response towards ERBB2-targeting drugs.

Increasing the efficacy of targeted cancer therapies requires the identification of robust biomarkers suitable for patient stratification. This study focused on the identification of molecular mechanisms causing resistance against the anti-ERBB2-directed therapeutic antibodies trastuzumab and pertuzumab presently used to treat patients with ERBB2-amplified breast cancer. Immunohistochemistry and clinical data were evaluated and yielded evidence for the existence of ERBB2-amplified breast cancer with high-level epidermal growth-factor receptor (EGFR) expression as a separate tumor entity. Because the proto-oncogene EGFR tightly interacts with ERBB2 on the protein level, the hypothesis that high-level EGFR expression might contribute to resistance against ERBB2-directed therapies was experimentally validated. SKBR3 and HCC1954 cells were chosen as model systems of EGFR-high/ERBB2-amplified breast cancer and exposed to trastuzumab, pertuzumab and erlotinib, respectively, and in combination. Drug impact was quantified in cell viability assays and on the proteomic level using reverse-phase protein arrays. Phosphoprotein dynamics revealed a significant downregulation of AKT signaling after exposure to trastuzumab, pertuzumab or a coapplication of both antibodies in SKBR3 cells but no concomitant impact on ERK1/2, RB or RPS6 phosphorylation. On the other hand, signaling was fully downregulated in SKBR3 cells after coinhibition of EGFR and ERBB2. Inhibitory effects in HCC1954 cells were driven by erlotinib alone, and a significant upregulation of RPS6 and RB phosphorylation was observed after coincubation with pertuzumab and trastuzumab. In summary, proteomic data suggest that high-level expression of EGFR in ERBB2-amplified breast cancer cells attenuates the effect of anti-ERBB2-directed antibodies. In conclusion, EGFR expression may serve as diagnostic and predictive biomarker to advance personalized treatment concepts of patients with ERBB2-amplified breast cancer.

Alcohol-induced neuronal death in central extended amygdala and pyriform cortex during the postnatal period of the rat.

Mothers who consume alcohol during pregnancy may cause a neurotoxic syndrome defined as fetal alcohol spectrum disorder (FASD) in their offspring. This disorder is characterized by reduction in brain size, cognitive deficits and emotional/social disturbances. These alterations are thought to be caused by an alcohol-induced increase in apoptosis during neurodevelopment. Little is known about neuroapoptosis in the central extended amygdala and the pyriform cortex, which are key structures in emotional/social behaviors. The goal of this study was to determine the vulnerability of neuroapoptotic alcohol effects in those areas. Rats were administered alcohol (2.5g/kg s.c. at 0 and 2h) or saline on postnatal day (PND) 7, 15 and 20. The Amino-cupric-silver technique was used to evaluate neurodegeneration and immunohistochemistry to detect activated caspases 3-8 and 9 at 2h, 4, 6, 8, 12 and 24h after drug administration. We measured blood alcohol levels each hour, from 2 to 8h post second administration of alcohol in each of the ages studied. Results showed alcohol induced apoptotic neurodegeneration in the central extended amygdala on PND 7 and 15, and pyriform cortex on PND 7, 15 and 20. These structures showed activation of caspase 3 and 9 but not of caspase 8 suggesting that alcohol-induced apoptosis could occur by the intrinsic pathway. The pharmacokinetic differences between ages did not associate with the neurodegeneration age dependence. In conclusion, these limbic areas are damaged by alcohol, and each one has their own window of vulnerability during the postnatal period. The possible implications in emotional/social features in FASD are discussed.

First Report of a New Wheat Leaf Rust (Puccinia triticina) Race with Virulence for Lr12, 13, and 37 in South Africa.

A new race of Puccinia triticina was collected from common wheat (Triticum aestivum) in the Eastern and Western Cape provinces during the annual rust survey in 2009. Six single-pustule isolates from a field collection, which were shown to be a new race in preliminary analyses, were inoculated onto seedlings of 16 Thatcher (Tc) near-isogenic differential lines (1) and other tester lines with known Lr genes. Standard procedures for inoculation, incubation, and rust evaluation were followed (4) and all infection studies were repeated. The low infection type of Lr18 was confirmed at 18°C. All six isolates were avirulent (infection types [ITs] 0; to 2) to Lr1, 2a, 2c, 9, 11, 16, 18, and 24 and virulent (ITs 3 to 4) to Lr3, 3ka, 10, 14a, 17, 26, 30, B, and Tc (control). The new race, named 3SA145 according to the ARC-Small Grain Institute notation, corresponds to race CCPS in the North American system (1). On the basis of seedling ITs of the extended Lr gene set, 3SA145 was avirulent (ITs 0; to 22+) to Lr2b, 19, 21, 23, 25, 28, 29, 32, 36 (E84081), 38, 45, 47 (KS90H450), 50 (KS96WGRC36), 51 (R05), and 52 and virulent to Lr3bg, 15, 20 (Thew), 27+31 (Gatcher), and 33. Lines containing the adult plant resistance (APR) genes Lr12 (RL6011, IT 3++), Lr13 (CT263, IT 3), Lr22b (Tc, IT 4), and Lr37 (RL6081, IT 3) were susceptible in the adult stage to 3SA145, whereas lines with the APR genes Lr22a (RL6044, IT ;1), Lr34 (RL6058, IT Z1), and Lr35 (RL6082, IT ;1) were resistant in controlled infection studies in a greenhouse. A control, the common race (3SA133), was virulent only on Tc adult plants. In seedlings, 3SA133 was avirulent to Lr15, 17, 26, and 27+31, but unlike 3SA145, it was virulent to Lr1, 2c, 11, 18, 24, and 28. Races 3SA133 and 3SA145 did not differ in their virulence to the remaining seedling genes. Virulence to Lr37 has been reported in several countries, including Australia, Canada, Uruguay, and the United States (1,2). Prior to the detection of 3SA145, adult plants of RL6081 were resistant to all wheat leaf rust races in South Africa. In 2009, however, RL6081 showed severity levels of up to 30S at certain Western Cape trap plot sites. Of 124 South African bread wheat cultivars and advanced breeding lines tested at the seedling stage, 3SA145 was virulent to 48, whereas 3SA133 was virulent to 36 entries. A further six entries were heterogeneous in their reaction to 3SA145. In adult plant infection studies of 48 South African spring wheats in a greenhouse, 19 were susceptible (flag leaf IT ≥3) and 22 were resistant to 3SA145. Seven entries showed a Z3 flag leaf IT indicating adult plant resistance. According to a simple sequence repeat (SSR) study using 17 primer-pair combinations described by Szabo and Kolmer (3), 3SA145 showed 30% homology with the dominant South African races. Although virulence to Lr12 and Lr13 has been known in different leaf rust races in South Africa, to our knowledge, this is the first report of combined virulence to Lr12, 13, and 37. The SSR data and unique avirulence/virulence profile suggest that 3SA145 may be an exotic introduction to South Africa. References: (1) J. A. Kolmer et al. Plant Dis. 89:1201, 2005. (2) B. McCallum and P. Seto-Goh. Can. J. Plant Pathol. 31:80, 2009. (3) L. Szabo and J. Kolmer. Mol. Ecol. Notes 7:708, 2007. (4) T. Terefe et al. S. Afr. J. Plant Soil 26:51, 2009.

Efficacy of chlorhexidine, polihexanide and tissue-tolerable plasma against Pseudomonas aeruginosa biofilms grown on polystyrene and silicone materials.

BACKGROUND: The formation of biofilms is crucial in the pathogenesis of many acute and subacute microbial infections, including chronic wounds and foreign-body-related infections. Topical antimicrobial therapy with chemical antiseptics or physical treatment with tissue-tolerable plasma (TTP) may be promising to control bacterial infection. METHODS: We assessed the efficacy of 0.1% chlorhexidine digluconate (CHX), 0.02 and 0.04% polihexanide (polyhexamethylene biguanide, PHMB) and of TTP against Pseudomonas aeruginosa SG81 biofilm grown in microtitre plates (polystyrene) and on silicone materials in an artificial wound fluid. RESULTS: Overall, PHMB was as effective as CHX in reducing the total amount of biofilm (gentian violet assay) and in reducing the bacterial metabolism in biofilms (XTT assay). TTP also led to a significant reduction in colony-forming units. CONCLUSION: The antimicrobial activity of PHMB in biofilms is comparable to that of CHX. TTP could become an interesting physical alternative to chemical antisepsis in the future.

Antiseptic efficacy and tolerance of tissue-tolerable plasma compared with two wound antiseptics on artificially bacterially contaminated eyes from commercially slaughtered pigs.

AIM: To compare the tissue tolerance and efficacy of two wound antiseptics with tissue-tolerable plasma (TTP) on enucleated contaminated eyes from slaughtered pigs in order to draw consequences for the use of TTP on wounds. METHOD: The corneas of extracted eyes were contaminated with Staphylococcus aureus or Pseudomonas aeruginosa. One and 10 min after application of 10% povidone (PVP)-iodine and 0.04% polyhexanide, respectively, the eyes were rinsed with inactivating solution. To test TTP, the plasma pen meandered over the eyes at a speed of 30 mm/s and a distance of 5 mm; the eyes were then rinsed with balanced salt solution. The reduction factor was calculated by the difference between the logarithm of colony-forming units in the rinse before and after antisepsis or TTP application. RESULTS: The efficacy of TTP (reduction factor 2.4-2.9) was significantly higher (p < 0.001) than that of PVP-iodine and polyhexanide (reduction factor 1.7-2.1). CONCLUSION: TTP is more effective than the tested wound antiseptics. The lack of histological damage to the eyes of slaughtered pigs would seem to make its use as a wound antiseptic a viable alternative. In contrast to antiseptics, it supplies additional energy in the form of heat, electric fields and radicals by TTP.

Involvement of AMPA/kainate-excitotoxicity in MK801-induced neuronal death in the retrosplenial cortex.

MK801 is a prototypical non-competitive NMDA receptor-antagonist that induces behavioural changes and reversible toxicity at low doses, while at higher doses triggers neuronal death that mainly affects the retrosplenial cortex (RSC) and to a lesser extent other structures such as the posterolateral cortical amygdaloid nucleus (PLCo). The mechanism of MK801-induced neurodegeneration remains poorly understood. In this study we analysed the participation of GABA-ergic and glutamatergic neurotransmission in MK801-induced neuronal death. We used a single i.p. injection of MK801 (2.5 mg/kg) that induced moderate neuronal death in the RSC and PLCo of female rats, and combined this treatment with the i.p., i.c.v., or intra-RSC infusion of drugs that are selective agonists or antagonists of the GABA-ergic or glutamatergic neurotransmission. We found that neuronal death in the RSC, but not the PLCo, was significantly reduced by the i.p. injection of thiopental, and the i.c.v. application of muscimol, both GABA-A agonists. MK801-toxicity in RSC was abrogated by intra-RSC infusion of muscimol, but the GABA antagonist picrotoxin had no effect. HPLC-analysis showed that levels of glutamate, but not GABA, in the RSC decreased after i.p. treatment with MK801. Intra-RSC infusion of MK801 did not enhance toxicity triggered by the i.p. injection of MK801, indicating that toxicity is not due to direct blockade of NMDA receptors in RSC neurons. MK801-toxicity in the RSC was abrogated by i.c.v. and intra-RSC infusions of the AMPA/kainate antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX). Interestingly, i.c.v. application of neither muscimol or DNQX inhibited MK801-toxicity in the PLCo, suggesting that the mechanism of neuronal death in the RSC and the PLCo might be different. 1-naphthylacetyl spermine trihydrochloride (NASPM), which blocks Ca2+ permeable AMPA/kainate receptors, also reduced MK801-induced toxicity in the RSC. Intra-RSC infusion of AMPA or kainic acid alone promoted death of RSC neurons and was reminiscent of the degeneration induced by the i.p. treatment with MK801. Collectively, these experiments provide evidence for an AMPA/kainate-dependent mechanism of excitotoxicity in the death of RSC neurons after i.p. treatment with MK801.

Explicit memory bias for positively valenced body-related cues in women with binge eating disorder.

Overweight women with and without binge eating disorder (BED) are characterized by a marked body dissatisfaction, which may in part be due to the negative comments about their weight. Weight-related teasing and discrimination is reported both by healthy overweight women and women with BED, whereas body dissatisfaction is markedly increased among women with BED. Therefore, a memory bias for negatively valenced body-related cues is suspected to occur as a mediating factor in women with BED. In an experimental study, 18 women with BED were compared to 18 overweight healthy female controls (HC) on a free recall task containing four word categories: positively valenced with and without body-related content and negatively valenced with and without body-related content. While both groups showed a bias towards negatively valenced shape-/weight-related words, women with BED retrieved positively valenced shape-/weight-related words significantly less often compared to overweight HC. Findings suggest that it may be the reduced ability to attend to positively valenced shape-/weight-related information, rather than the activation of negative body schemata that differentiates overweight women with BED from overweight women without BED. Results are discussed in the context of cognitive biases in the maintenance of body dissatisfaction.

First Report of Virulence for the Wheat Leaf Rust (Puccinia triticina) Resistance Gene Lr32 in South Africa.

The wheat leaf rust resistance gene Lr32 was transferred from Aegilops tauschii Coss. to bread wheat (Triticum aestivum L.) (1). Despite virulence for Lr32 in some isolates from Bulgaria, Israel, and Turkey, the gene has been reported to be effective in Australia, Mexico, the United States, and South Africa (1,2). A leaf rust isolate that differed in its avirulence/virulence profile from previously recorded races of Puccinia triticina Eriks. in South Africa was collected from triticale (× Triticosecale) in the Western Cape in 2005. According to the South African leaf rust differential set (3), this isolate (UVPt19) was avirulent for Lr3a, 3bg, 3ka, 10, 11, 16, 20, 26, and 30 and virulent for Lr1, 2a, 2b, 2c, 14a, 15, 17, 24, and Thatcher (Tc, control). Except for Lr20 in cv. Thew, all differentials are Tc near-isogenic lines. In comparison with known South African races (3), it differed from race 3SA132 at the Lr10 locus. Using standard rust pathology protocols (3), an expanded set of Lr gene lines (non Tc lines indicated) showed that UVPt19 is avirulent on wheat seedlings containing Lr9, 19, 21, 25, 27+31 (Gatcher), 29, 36 (ER84018), 37, 41 (KS91WGRC10), 44, 45, 47 (KS90H450), 50 (KS96WGRC36), 51 (R05), and 52, and virulent for Lr12, 22a, 23, 28, 32, 33, and 35. In the seedling stage, UVPt19 was virulent for the temperature sensitive genes Lr13, 18, and 34 at 25°C, but produced lower infection types (ITs) on Lr18 and 34 at 14 to 18°C. Seedlings of Pavon 76 (Lr46) were resistant (IT ;1=) to UVPt19. The susceptible response of lines carrying Lr32 was confirmed by high ITs (3++4) on RL5713/2*Mq, RL6086 (TcLr32), and RL5713/2*Mq//6*Palmiet. A control isolate (UVPt9) produced ITs ;1+, ;1+, and ;;1= on these lines, respectively. UVPt19 was virulent on line RL6092 (TcLr20) but avirulent on Thew. When tested on adult plants of lines RL6011 (TcLr12), CT263 (TcLr13), RL6044 (TcLr22a), RL6058 (TcLr34), RL6082 (TcLr35), RL6081 (TcLr37), and Tc (control), UVPt19 was only virulent (IT 3+) on CT263 and Tc. Flag leaves of RL6011 (IT ;1), RL6044 (IT 1), RL6058 (IT Z3-), RL6082 (IT 0;), and RL6081 (IT ;1) were resistant. UVPt19 was virulent on seedlings of 11 of 13 triticale cultivars and lines tested as opposed to UVPt9, which was virulent to only one entry. From a collection of 105 South African bread wheat cultivars and elite breeding lines, UVPt19 was virulent on 13 and five were mixed in their response to this isolate. All IT experiments were repeated. Although virulence has emerged for Lr32 in South Africa, the gene has not been used in local cultivars. Previously, McIntosh et al. (1) also reported that Lr32 has not been exploited in wheat production. On the basis of current evidence, UVPt19 appears to be potentially more damaging to triticale than bread wheat. Furthermore, the race seems rare because it was not collected in a recent wheat leaf rust survey in South Africa (3). References: (1) R. A. McIntosh et al. The Wheat Rusts: An Atlas of Resistance Genes, CSIRO-Kluwer, Dordrecht, the Netherlands, 1995. (2) Z. A. Pretorius. Phytophylactica 21:195, 1989. (3) T. Tarekegn et al. S. Afr. J. Plant Soil 26:51, 2009.

First Report of a Puccinia graminis f. sp. tritici Race Virulent to the Sr24 and Sr31 Wheat Stem Rust Resistance Genes in South Africa.

Isolates of Puccinia graminis f. sp. tritici belonging to the Ug99 race group are virulent to a broad spectrum of resistance genes, rendering most of the world's wheat germplasm susceptible to stem rust (3). Following the initial detection of Ug99 (TTKSK, North American [NA] race notation) in Uganda, virulence to the widely used Sr31 resistance gene has been reported from Kenya, Ethiopia, Sudan, and Iran (2,3). In November 2009, a wheat genotype suspected to carry Sr31 showed a susceptible response to stem rust in a disease nursery (29°08'05.02''S, 30°38'29.18''E), inoculated with race TTKSP, near Greytown in KwaZulu-Natal, South Africa. Inoculation of urediniospores of the field collection (isolate UVPgt60) onto seedlings of line Federation4*/Kavkaz confirmed virulence for Sr31. In three independent, replicated, and comparative seedling tests, eight single-pustule isolates of UVPgt60 all typed to race PTKST following the NA race nomenclature. These isolates produced compatible infection types (ITs) (3+ to 4) on the Sr31 testers Gamtoos, Sr31/6*LMPG, Federation4*/Kavkaz, Kavkaz, and Clement, whereas isolate UVPgt59 (TTKSP) was avirulent (ITs ;1 to 1) on these genotypes. In addition to Sr31 virulence, the new race differed from TTKSP by producing a lower IT (2 to 2++) on Cns_T.mono_ deriv., the accepted entry for Sr21 in the NA differential set. The UVPgt60 isolates were clearly avirulent on Einkorn (Sr21) (IT ;1=), a response that also differed from those produced by BPGSC, TTKSF, and TTKSP (IT 2). With the exception of Sr21, UVPgt60 isolates had a virulence pattern similar to race TTKST (1), notably the virulence combination for Sr24 and Sr31. Isolate UVPgt60.6 was randomly selected for testing on additional Sr genes and South African wheat cultivars and breeding lines. Similar to the race identification experiments seedling tests were duplicated and compared with reactions produced by TTKSP and other races. Greenhouse temperatures for all seedling tests ranged between 18 and 25°C. On the basis of primary leaf responses, PTKST is avirulent (ITs 0; to 2++) for Sr13, 14, 21, 22, 25, 26, 27, 29, 32, 33, 35, 36, 37, 39, 42, 43, 44, Em, Tmp, and Satu and virulent (ITs 3 to 4) for Sr5, 6, 7b, 8a, 8b, 9a, 9b, 9d, 9e, 9g, 10, 11, 16, 17, 24, 30, 31, 34, 38, 41, and McN. From 103 South African wheat cultivars and lines tested as seedlings, 59 and 47 were susceptible (IT ≥ 3) to races PTKST and TTKSP, respectively. Simple-sequence repeat analysis (4) with selected primer pairs showed that PTKST clusters with isolates belonging to the Ug99 lineage. Subsequent to the collection made at Greytown, stem rust sampled in December 2009 from naturally infected breeders' lines at Cedara (29°32'19.59''S, 30°16'03.50''E), KwaZulu-Natal, revealed five isolates with a virulence profile similar to PTKST. On the basis of current evidence it appears that PTKST may be an introduction to South Africa rather than a single-step mutation from local stem rust races. References: (1) Y. Jin et al. Plant Dis. 92:923, 2008. (2) K. Nazari et al. Plant Dis. 93:317, 2009. (3) R. P. Singh et al. Adv. Agron. 98:271, 2008. (4) B. Visser et al. Mol. Plant Pathol. 10:213, 2009.