Automated Region-based Prostate Cancer Cell Nuclei Localization. Part of a Prognostic Modality Tool for Prostate Cancer Patients.

BACKGROUND: Prostate cancer is a disease of disrupted cell genomes. Quantification of DNA from cytology preparations can yield prognostic information about tissue biological behaviors; however, this process is very labor-intensive to perform. Quantitative digital pathology can measure the structural chromatin changes associated with neoplasia and can enable prognostic and predictive assays based on imaging of sectioned prostate tissue. OBJECTIVE: To design an automated system to recognize and localize cell nuclei in images of stained sectioned tissue (first step in enabling quantitative digital pathology). STUDY DESIGN: Images of Feulgen-thionin-stained prostate cancer tissue microarray constructed from the surgical specimens of 33 prostate cancer patients were acquired for this study. We implemented a new image segmentation technique to overcome tissue complexity, cell clusters, background noise, image and tissue inhomogeneities, and other imaging issues that introduce uncertainties into the segmentation method and developed a fully automated system to localized prostate cell nuclei. RESULTS: We applied our algorithm on our dataset and obtained a 96.6% true-positive rate and a 12% false-positive rate. CONCLUSION: In this paper we present a new method to automatically localize thionin-stained prostate cancer cells, enabling the extraction of various nuclear and cell sociology features with high precision.

Energy analyses and greenhouse gas emissions assessment for saffron production cycle.

Population growth and world climate changes are putting high pressure on agri-food production systems. Exacerbating use of energy sources and expanding the environmental damaging symptoms are the results of these difficult situations. This study was conducted to determine the energy balance for saffron production cycle and investigate the corresponding greenhouse gas (GHG) emissions in Iran. Saffron (Crocus sativus L.) is one of the main spice that historically cultivated in Iran. Data were obtained from 127 randomly selected saffron growers using a face to face questionnaire technique. The results revealed that in 5 years of saffron production cycle, the overall input and output energy use were to be 163,912.09 and 184,868.28 MJ ha(-1), respectively. The highest-level of energy consumption belongs to seeds (23.7 %) followed by chemical fertilizers (23.4 %). Energy use efficiency, specific energy, net energy, and energy productivity of saffron production were 1.1, 13.4 MJ kg(-1), 20,956.2 MJ ha(-1), and 0.1 kg MJ(-1), respectively. The result shows that the cultivation of saffron emits 2325.5 kg CO2 eq. ha(-1) greenhouse gas, in which around 46.5 % belonged to electricity followed by chemical fertilizers. In addition the Cobb-Douglas production function was applied into EViews 7 software to define the functional relationship. The results of econometric model estimation showed that the impact of human labor, electricity, and water for irrigation on stigma, human labor, electricity, and seed on corm and also human labor and farmyard manure (FYM) on flower and leaf yield were found to be statistically significant. Sensitivity analysis results of the energy inputs demonstrated that the marginal physical productivity (MPP) worth of electricity energy was the highest for saffron stigma and corm, although saffron flower and leaf had more sensitivity on chemicals energy inputs. Moreover, MPP values of renewable and indirect energies were higher than non-renewable and direct energies, respectively.

Activation of GABA-A receptors during postnatal brain development increases anxiety- and depression-related behaviors in a time- and dose-dependent manner in adult mice.

Disturbances of the gamma-amino butyric acid-ergic (GABAergic) system during postnatal development can have long-lasting consequences for later life behavior, like the individual's response to stress. However, it is unclear which postnatal windows of sensitivity to GABA-ergic modulations are associated with what later-life behavioral outcomes. Therefore, we sought to determine whether neonatal activation of the GABA-A receptor during two postnatal periods, an early window (postnatal day 3-5) and a late window (postnatal day 14-16), can affect anxiety- and depression-related behaviors in male mice in later life. To this end, mice were treated with either saline or muscimol (50, 100, 200, 300 and 500µg/kg) during the early and late postnatal periods. An additional group of mice was treated with the GABA-A receptor antagonist bicuculline+muscimol. When grown to adulthood male mice were exposed to behavioral tests to measure anxiety- and depression-related behaviors. Baseline and stress-induced corticosterone (CORT) levels were also measured. The results indicate that early postnatal and to a lesser extent later postnatal exposure to the GABA-A receptor agonist muscimol increased anxiety-like behavior and stress-induced CORT levels in adults. Moreover, the early postnatal treatment with muscimol increased depression-like behavior with increasing baseline CORT levels. The anxiogenic and depression-like later-life consequences could be antagonized by bicuculline. Our findings suggest that GABA-A receptor signaling during early-life can influence anxiety- and depression-related behaviors in a time- and dose-dependent manner in later life. Our findings help to increase insight in the developmental mechanisms contributing to stress-related disorders.

Neonatal NMDA receptor blockade alters anxiety- and depression-related behaviors in a sex-dependent manner in mice.

There is increasing evidence that N-methyl-D-aspartate (NMDA) receptor blockade in the neonatal period has a long-lasting influence on brain and behavior development and has been linked to an increased risk for neuropsychiatric disorders in later life. We sought to determine whether postnatal NMDA receptor blockade can affect normal development of body weight, corticosterone levels, anxiety- and depression-related behaviors in male and female mice in adulthood. For this purpose, male and female NMRI mice were treated with either saline or phencyclidine (PCP; 5 and 10 mg/kg, s.c.) on postnatal days (PND) 7, 9, and 11, and then subjected to different behavioral tests, including open field, elevated plus-maze, elevated zero-maze, light-dark box, tail suspension test and forced swimming test in adulthood. The results indicated that neonatal PCP treatment reduced body weight during neonatal and adulthood periods, and did not alter baseline corticosterone levels in both male and female mice. Moreover, this study obtained some experimental evidence showing the PCP at dose of 10 mg/kg increases stress-induced corticosterone levels, anxiety- and depression-related behaviors in males, while decreasing levels of anxiety without any significant effect on depression in female mice in adulthood. These data support the argument that neonatal NMDA receptor blockade can lead to behavioral abnormalities and psychiatric diseases in adulthood. Collectively, our findings suggest that neonatal exposure to PCP may have profound effects on the development of anxiety- and depression-related behaviors in a sex- and dose-dependent manner in mice.

Impacts of early intervention with fluoxetine following early neonatal immune activation on depression-like behaviors and body weight in mice.

Several reports have suggested that early neonatal immune activation adversely influences the hypothalamic-pituitary-adrenal (HPA) axis development in humans and animal models. In addition, there have been several studies indicating that early intervention with fluoxetine (FLX) can alter HPA axis development and function, and prevent occurrence of behavioral abnormalities induced by common early-life insults. The present study aims to investigate the effects of early intervention with FLX following early neonatal immune activation on depression-like behaviors and body weight in mice. Neonatal mice in their postnatal days (PNDs) 3 and 5 received either lipopolysaccharide (LPS; 50 µg/kg, s.c.) or saline treatment, then male and female mice of both neonatal intervention groups received oral administration of FLX (5 and 10 mg/kg/day) or water via regular drinking bottles during the periadolescent period (PNDs 35-65). The results showed that neonatal LPS exposure elevated depression-like behaviors accompanied by increasing corticosterone levels in adulthood and decreasing body weight during neonatal and adolescent periods. Furthermore, the periadolescent FLX treatment inhibited the depression-like behaviors induced by neonatal infection in both sexes. This study obtained some experimental evidence indicating the potential adverse impacts of the FLX on normal behavioral development in male control animals. In conclusion, our findings suggest that an early pharmacological intervention with FLX may prevent emergence of depression-like behaviors induced by neonatal immune challenge without any detrimental effect on health in a sex- and dose-dependent manner in mice.

Photothermal release of small molecules from gold nanoparticles in live cells.

The ability of gold (Au) nanoparticles (NPs) to generate heat efficiently by absorbing visible and near-infrared (NIR) light holds great promise as a means to trigger chemical and biochemical events near the NPs. Previous demonstrations show that pulsed laser irradiation can selectively elicit the release of a fluorescent dye covalently anchored to the NP surface through a heat-labile linker without measurably changing the temperature of the surroundings. This article reports that the authors demonstrate the biological efficacy of this approach to photodelivery by showing that the decorated Au NPs are rapidly internalized by cells, are stable under physiological conditions, are nontoxic, and exhibit nonlethal photorelease following exposure to pulsed laser radiation. These observations, further supported by the versatility of our delivery motif, reaffirm the potential for further development of nonlethal photothermal therapeutics and their future relevance to such fields as gene therapy and stem-cell differentiation.

5HT(1A) and 5HT(1B) receptors of medial prefrontal cortex modulate anxiogenic-like behaviors in rats.

Medial prefrontal cortex (MPFC) is one of the brain regions which play an important role in emotional behaviors. The purpose of the present study was to evaluate the role of 5HT(1A) and 5HT(1B) receptors of the MPFC in modulation of anxiety behaviors in rats. The elevated plus maze (EPM) which is a useful test to investigate the effects of anxiogenic or anxiolytic drugs in rodents, was used. Bilateral intra-MPFC administration of 5HT(1A) receptor agonist, 8-OH-DPAT (5, 10, and 50 ng/rat) decreased the percentages of open arm time (OAT%) and open arm entries (OAE%), indicating an anxiogenic response. Moreover, administration of 5HT(1A) receptor antagonist, NAN-190 (0.25, 0.5, and 1 µg/rat) significantly increased OAT% and OAE%. Pre-treatment administration of NAN-190 (0.5 µg/rat), which was injected into the MPFC, reversed the anxiogenic effects of 8-OH-DPAT (5, 10, and 50 ng/rat). Intra-MPFC microinjection of 5HT(1B) receptor agonist, CGS-12066A (0.25, 0.5, and 1 µg/rat) significantly decreased OAT% and OAE%, without any change in locomotor activity, indicating an anxiogenic effect. However, injection of 5HT(1B) receptor antagonist, SB-224289 (0.5, 1, and 2 µg/rat) into the MPFC showed no significant effect. In conclusion, these findings suggest that 5HT(1A) and 5HT(1B) receptors of the MPFC region modulate anxiogenic-like behaviors in rats.

An efficient method based on the photothermal effect for the release of molecules from metal nanoparticle surfaces.

Please release me: The heat generated when metal nanoparticles absorb light results in a significant increase in the temperature of the environment around the particles and is used to selectively break bonds within a molecular system anchored to the nanoparticle surface (see picture). This process represents an advantageous and more universal method to deliver chemicals locally, while avoiding excessive tissue damage.