Fluoxetine Partly Exerts its Actions Through GABA: A Neurochemical Evidence

Fluoxetine, as a serotonin re-uptake inhibitor augments serotonin concentration within the synapse by inhibiting the serotonin transporter. The contribution of amino acids has also been shown in depression. We hypothesized that fluoxetine exerts its actions at least in part by intervening brain signaling operated by amino acid transmitters. Therefore the aim of this study is to supply neurochemical evidence that fluoxetine produces changes in amino acids in cerebrospinal fluid of rats. Sprague-Dawley rats were anesthetized and concentric microdialysis probes were implanted stereotaxically into the right lateral ventricle. Intraperitoneal fluoxetine (2.5 or 5 mg/kg) or physiological saline was administered and the probes were perfused with artificial cerebrospinal fluid at a rate of 1 μl/min. In the chronic fluoxetine group, the rats were treated daily with oral fluoxetine solution or inert syrup for 3 weeks. The microdialysis probes were placed on the 21st day and perfused the next day. Fluoxetine was ineffective in changing the cerebrospinal fluid GABA levels at the dose of 2.5 mg/kg but produced a significant increase in the perfusates following injection of 5 mg/kg of fluoxetine (P < 0.05). Oral fluoxetine administration (5 mg/kg) for 21 days also elevated the CSF GABA levels by approximately 2-fold (P < 0.05). l-glutamic acid levels were not affected in all groups. These neurochemical findings show that fluoxetine, a selective serotonin re-uptake inhibitor affects brain GABA levels indirectly, and our results suggest that acute or chronic effects may be involved in beneficial and/or adverse effects of the drug.     

Pressure-related Increase of Asymmetric Dimethylarginine Caused by Hyperbaric Oxygen in the Rat Brain: A Possible Neuroprotective Mechanism

A decrease in nitric oxide availability in the brain tissue due to the inhibition of nitric oxide synthase (NOS) activity during the early phases of hyperbaric oxygen (HBO) exposure was found to be involved in hyperoxic vasoconstriction leading to reduced regional cerebral blood flow. We hypothesized that the concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), may be an important factor during this hyperoxic vasoconstriction state. Rats were exposed to 1, 2 and 3 atmospheres pure oxygen for two hours. A fourth group of animals served as control. Asymmetric dimethylarginine, L-Arginine and nitrite/nitrate (NO_x) concentrations were measured from deproteinized rat brain cytosols. In rat brains exposed to 3 atmospheres O₂, ADMA and L-Arginine levels were found to be significantly higher and NO_x significantly lower than control levels. Additionally, statistically significant correlations between ADMA and L-Arginine, and ADMA and NO_x concentrations were detected. In conclusion, this is the first study indicating increased ADMA levels in rat brains exposed to HBO. The simultaneously decreased NO_x values suggest that ADMA elevation resulted in NOS inhibition and therefore may be responsible for the early phase hyperoxic vasoconstriction.     

The effects of a low dose of cabergoline on induction of estrus and pregnancy rates in anestrous bitches

This is the first report of successful induction of normal estrus and ovulation in breeder bitches with as a low dose as 0.6 microg/kg/day of cabergoline formulation marketed for use in women. Sixty-one pure breed bitches from various breeds were used in the study at their already determined periods of anestrus. Twenty-four dogs formed the control group, while 37 bitches were administered with two different doses of cabergoline (recommended dose group, n=10, 5 microg/kg/day and low dose group, n=27, 0.6 microg/kg/day). Induced estrus rates and mean treatment and proestrus durations of dogs in these two dose groups were compared. At the second phase of the study, the effects of 500 IU human chorionic gonadotropin (hCG) administered on days 1 and 3 of estrus induced by the low dose of cabergoline, on the duration of behavioral estrus, ovulation rates, pregnancy rates and the number of offspring were investigated. For this purpose, the dogs with signs of proestrus (22/27) following the treatment in the low dose group were assigned into two subgroups. Five hundred IU of hCG (Pregnyl, Organon, Turkey) was intramuscularly administered to eight of these dogs [low dose (hCG+) group] on days 1 and 3 of estrus. The remaining 14 dogs were not treated with hCG [low dose (hCG-) group]. An aqueous solution of cabergoline (Dostinex, Pharmacia, Italy) was orally administered until 2 day after the onset of proestrus or for a maximum of 42 days. Blood samples were taken daily from all treatment and 11 control bitches during the first five days of behavioral estrus to measure progesterone concentrations. In the recommended dose and low dose groups, estrus was induced between days 8-45 and 4-48 (mean: 23.63+/-14.33 and 24.41+/-14.31 days), in the ratio of 80.0 and 81.5%, respectively (p>0.05). In both dose groups, post-treatment interestrous intervals were significantly shorter than both those of the control group and their own pre-treatment interestrous intervals (p<0.05). Ovulation rates, pregnancy rates and mean number of offspring delivered by the dogs in the recommended dose, low dose (hCG-), low dose (hCG+) and control groups were found to be similar (p>0.05). However, the mean duration of behavioral estrus of the dogs in the low dose (hCG+) group was found to be significantly longer compared to dogs in all other groups (p<0.05). In both dose groups, no correlation could be found between the anestrus stages and treatment durations (p>0.05). Shortly, it has been concluded from the study that (1) normal and fertile estrus can be induced more economically in bitches during different stages of anestrus using as a low dose of 0.6 microg/kg of cabergoline formulation marketed for use in women, and that (2) hCG injections on days 1 and 3 of the estrus induced by this method has no positive effects on the ovulation rates, pregnancy rates and the number of offspring per pregnancy.     

Relationship between bovine fertility and the number of spermatozoa penetrating the cervical mucus within straws

In this study, by using a recently developed test technique, the relationship between the total spermatozoa number penetrating determined sites of bovine cervical mucus in straws and potential fertility of bulls, and other spermatological characteristics were investigated. Furthermore, we aimed to determine the effect on the test results, of two different incubation temperatures (37 and 41 degrees C) and two sperm penetration distance ranges (PDRs). Frozen semen samples of six Holstein bulls were used in the study. The bulls were divided into two fertility groups (high and low fertility) according to the "non-return rates" (NRR). For the penetration test, cervical mucus was drawn into transparent plastic straws and incubated with semen at 37 and 41 degrees C for 15 min. After the incubation, straws were frozen in liquid nitrogen vapour and stored at -20 degrees C. On the evaluation day, concentrations of spermatozoa penetrated to the PDRs, each of which was 2.5 mm, between 32.5 and 35 mm (first penetration distance range, PDR1), and 50 and 52.5 mm (second penetration distance range, PDR2) distance in the straws from the open end, were measured. When compared with the low fertility group, bulls from the high fertility group showed a higher number of spermatozoa at the determined PDRs, and a significant positive correlation was found between the total number of spermatozoa at the penetration distances and the NRR scores of the bulls.     

The effects of boric acid-induced oxidative stress on antioxidant enzymes and survivorship in Galleria mellonella

Larvae of the wax moth, Galleria mellonella (L.), were reared from first instar on a diet supplemented with 156, 620, 1,250, or 2,500 ppm boric acid (BA). The content of malondialdehyde (MDA, an oxidative stress indicator), and activities of the antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glutathione peroxidase (GPx)] were determined in the fat body and hemolymph in the 7th instar larvae and newly emerged pupae. Relative to control larvae, MDA was significantly increased in larval hemolymph, larval and pupal fat body, but decreased in the pupal hemolymph. Insects reared on diets with 156- and 620-ppm BA doses yielded increased SOD activity but 1,250- and 2,500-ppm doses resulted in decreased SOD activity in larval hemolymph. SOD activity was significantly increased but CAT was decreased in the larval fat body. High dietary BA treatments led to significantly decreased GST activity. However, they increased GPx activity in larval hemolymph. Dietary BA also affected larval survival. The 1,250- and 2,500-ppm concentrations led to significantly increased larval and pupal mortality and prolonged development. In contrast, the lowest BA concentration increased longevity and shortened development. We infer that BA toxicity is related, at least in part, to oxidative stress management.     

Sulfur and nitrogen nutrition status in flag leaf and shoot samples collected from wheat growing areas in Çukurova,Central Anatolia and GAP regions of Turkey

Sulfur (S) deficiency in soils and plants has been increased in the recent decade which is reducing crop yield and quality. Unfortunately, no extensive study has been conducted on S nutritional status of plants in Turkey. In this study, soil and plant samples were collected from Çukurova, Central Anatolia and GAP regions where wheat is extensively cultivated. Plant samples either as flag leaf or the whole shoot were collected depending on growth stage of wheat crop at sample collection. Similarly, surface (0–20 cm) and sub-surface (20–40 cm) soil samples were collected from plant sampling sites and a total 963 plant and 1947 soil samples were collected during the study. The S concentration in flag leaf samples varied between 0.18 and 0.67%, 0.11–0.59% and 0.17–0.82% for central Anatolia, Çukurova and GAP regions, respectively. According to S concentration in flag leaf samples, 99% of the plants in Çukurova region were found sufficient in S nutrition. However, 49% of the samples collected from central Anatolia and GAP regions were deficient in S. Critical N:S ratio indicating S nutrition status of plants was lower than the widely accepted critical value of 17. This low N:S ratio was a consequence of deficient N nutrition rather than S nutrition. Moreover, it was observed that plant available SO₄-S concentration of soils varied within and among sampled provinces with an average value of 20.6 and 31.6 mg kg^?1 for surface and sub-surface samples, respectively. The SO₄-S concentration increased with increasing soil depth. The results indicate a significantly positive correlation between S concentration in plant shoot and plant available SO₄-S concentration in soils. In conclusion, S-containing fertilizer use in central Anatolia and GAP regions must be considered as an important approach for the prevention of yield and quality losses. Furthermore, rapid and sensitive plant and soil analysis methods are needed, which must also consider the local and site-specific conditions.     

Genomic Analysis of Xanthomonas translucens Pathogenic on Wheat and Barley Reveals Cross-Kingdom Gene Transfer Events and Diverse Protein Delivery Systems

In comparison to dicot-infecting bacteria, only limited numbers of genome sequences are available for monocot-infecting and in particular cereal-infecting bacteria. Herein we report the characterisation and genome sequence of Xanthomonas translucens isolate DAR61454 pathogenic on wheat and barley. Based on phylogenetic analysis of the ATP synthase beta subunit (atpD) gene, DAR61454 is most closely related to other X. translucens strains and the sugarcane- and banana- infecting Xanthomonas strains, but shares a type III secretion system (T3SS) with X. translucens pv. graminis and more distantly related xanthomonads. Assays with an adenylate cyclase reporter protein demonstrate that DAR61454''s T3SS is functional in delivering proteins to wheat cells. X. translucens DAR61454 also encodes two type VI secretion systems with one most closely related to those found in some strains of the rice infecting strain X. oryzae pv. oryzae but not other xanthomonads. Comparative analysis of 18 different Xanthomonas isolates revealed 84 proteins unique to cereal (i.e. rice) infecting isolates and the wheat/barley infecting DAR61454. Genes encoding 60 of these proteins are found in gene clusters in the X. translucens DAR61454 genome, suggesting cereal-specific pathogenicity islands. However, none of the cereal pathogen specific proteins were homologous to known Xanthomonas spp. effectors. Comparative analysis outside of the bacterial kingdom revealed a nucleoside triphosphate pyrophosphohydrolase encoding gene in DAR61454 also present in other bacteria as well as a number of pathogenic Fusarium species, suggesting that this gene may have been transmitted horizontally from bacteria to the Fusarium lineage of pathogenic fungi. This example further highlights the importance of horizontal gene acquisition from bacteria in the evolution of fungi.     

Multitask learning over shared subspaces

This paper uses constructs from machine learning to define pairs of learning tasks that either shared or did not share a common subspace. Human subjects then learnt these tasks using a feedback-based approach and we hypothesised that learning would be boosted for shared subspaces. Our findings broadly supported this hypothesis with either better performance on the second task if it shared the same subspace as the first, or positive correlations over task performance for shared subspaces. These empirical findings were compared to the behaviour of a Neural Network model trained using sequential Bayesian learning and human performance was found to be consistent with a minimal capacity variant of this model. Networks with an increased representational capacity, and networks without Bayesian learning, did not show these transfer effects. We propose that the concept of shared subspaces provides a useful framework for the experimental study of human multitask and transfer learning.