Red white and blue – bright light effects in a diurnal rodent model for seasonal affective disorder

Despite the common use of bright light exposure for treatment of seasonal affective disorder (SAD), the underlying biology of the therapeutic effect is not clear. Moreover, there is a debate regarding the most efficacious wavelength of light for treatment. Whereas according to the traditional approach full-spectrum light is used, recent studies suggest that the critical wavelengths are within the range of blue light (460 and 484 nm). Our previous work shows that when diurnal rodents are maintained under short photoperiod they develop depression- and anxiety-like behavioral phenotype that is ameliorated by treatment with wide-spectrum bright light exposure (2500 lux at the cage, 5000 K). Our current study compares the effect of bright wide-spectrum (3,000 lux, wavelength 420- 780 nm, 5487 K), blue (1,300 lux, wavelength 420-530 nm) and red light (1,300 lux, wavelength range 600-780 nm) exposure in the fat sand rat (Psammomys Obesus) model of SAD. We report results of experiments with six groups of sand rats that were kept under various photoperiods and light treatments, and subjected to behavioral tests related to emotions: forced swim test, elevated plus maze and social interactions. Exposure to either intense wide-spectrum white light or to blue light equally ameliorated depression-like behavior whereas red light had no effect. Bright wide-spectrum white light treatment had no effect on animals maintained under neutral photoperiod, meaning that light exposure was only effective in the pathological-like state. The resemblance between the effects of bright white light and blue light suggests that intrinsically photosensitive retinal ganglion cells (ipRGCs) are involved in the underlying biology of SAD and light therapy.     

Enhanced levels of free and protein-bound threonine in transgenic alfalfa (Medicago sativa L.) expressing a bacterial feedback-insensitive aspartate kinase gene

Threonine, lysine, methionine, and tryptophan are essential amino acids for humans and monogastric animals. Many of the commonly used diet formulations, particularly for pigs and poultry, contain limiting amounts of these amino acids. One approach for raising the level of essential amino acids is based on altering the regulation of their biosynthetic pathways in transgenic plants. Here we describe the first production of a transgenic forage plant, alfalfa (Medicago sativa L.) with modified regulation of the aspartate-family amino acid biosynthetic pathway. This was achieved by over-expressing the Escherichia coli feedback-insensitive aspartate kinase (AK) in transgenic plants. These plants showed enhanced levels of both free and protein-bound threonine. In many transgenic plants the rise in free threonine was accompanied by a significant reduction both in aspartate and in glutamate. Our data suggest that in alfalfa, AK might not be the only limiting factor for threonine biosynthesis, and that the free threonine pool in this plant limits its incorporation into plant proteins.     

A hypomethylating variant of MTHFR, 677C>T, blunts the neural response to errors in patients with schizophrenia and healthy individuals

Background

Responding to errors is a critical first step in learning from mistakes, a process that is abnormal in schizophrenia. To gain insight into the neural and molecular mechanisms of error processing, we used functional MRI to examine effects of a genetic variant in methylenetetrahydrofolate reductase (MTHFR 677C>T, rs1801133) that increases risk for schizophrenia and that has been specifically associated with increased perseverative errors among patients. MTHFR is a key regulator of the intracellular one-carbon milieu, including DNA methylation, and each copy of the 677T allele reduces MTHFR activity by 35%.

Methodology/Principal Findings

Using an antisaccade paradigm, we found that the 677T allele induces a dose-dependent blunting of dorsal anterior cingulate cortex (dACC) activation in response to errors, a pattern that was identical in healthy individuals and patients with schizophrenia. Further, the normal relationship between dACC activation and error rate was disrupted among carriers of the 677T allele.

Conclusions/Significance

These findings implicate an epigenetic mechanism in the neural response to errors, and provide insight into normal cognitive variation through a schizophrenia risk gene.     

L'epoca Della Differenziazione Delle Gemme Fiorali Nell'olivo

Abstract

Calcium, as in general for all plants, is very important for fruit trees and a tight correlation between leaf content and cropping efficiency has been found.

The annual removal of calcium oxide of an orchard has been estimated in kg per hectare: pear 200, apple 180, peach 150, grape 60–130, olive 35–70, kiwi 55–60.

The rootstock affects the calcium uptake from the soil and content of the scion; frequently a higher calcium content is found in trees grafted an dwarfing rootstocks as pear on quince, apple on M9 and M26, peach on Damas.

By the horticultural point of view, calcium is responsible of two main problems: chlorosis due to high active Ca content in the soil and bitter pit, on the apposite, due to a low Ca level in the fruits.

From soil and leaf studies it seems clear that lime-induced Fe chlorosis results from two conditions: a) slow availability of Fe in the soil, and b) immobilization of Fe in the tree in forms that are not available for chlorophyll formation.

Breeding tolerant rootstocks has been the practical solution of chlorosis for most of the susceptible species.

Bitter pit is a physiological disorder of apple fruits, sometime already evident before picking, more frequently after harvesting, during the storage.

The prevention of the disorder is, essentially, a good horticultural practice (pruning, fertilization, irrigation, fruit thinning). Very effective are also Ca sprays as chloride or nitrate, or citrate, or phosphate, starting after setting, 4–5 times every 10–12 days.     

Plasmodium circumsporozoite protein promotes the development of the liver stages of the parasite

The liver stages of malaria are clinically silent but have a central role in the Plasmodium life cycle. Liver stages of the parasite containing thousands of merozoites grow inside hepatocytes for several days without triggering an inflammatory response. We show here that Plasmodium uses a PEXEL/VTS motif to introduce the circumsporozoite (CS) protein into the hepatocyte cytoplasm and a nuclear localization signal (NLS) to enter its nucleus. CS outcompetes NFkappaB nuclear import, thus downregulating the expression of many genes controlled by NFkappaB, including those involved in inflammation. CS also influences the expression of over one thousand host genes involved in diverse metabolic processes to create a favorable niche for the parasite growth. The presence of CS in the hepatocyte enhances parasite growth of the liver stages in vitro and in vivo. These findings have far reaching implications for drug and vaccine development against the liver stages of the malaria parasite.     

Effect of synthetic enantiomeric cannabinoids on platelet aggregation.

The effect of a synthetic pair of enantiomeric cannabinoids on platelet function was evaluated. The nonpsychotropic enantiomer, the 1,1-dimethylheptyl homolog of (+)-(3S,4S)-7-hydroxy-delta-6-tetrahydrocannabinol (HU-211), was found to be more active in inhibiting ADP-induced platelet aggregation than the highly psychotropic (-)-enantiomer (HU-210). The related (+)-(3R,4R) cannabinoid, HU-213, which lacks the 7-hydroxy moiety, exerted its inhibitory effect within a wider range of concentrations. The results indicate a differentiation between psychotropic activity and inhibition of platelet aggregation in the cannabinoid group of compounds.     

Cytokine milieu in renal cavities of immunocompetent mice in response to intravenous challenge of Aspergillus flavus leading to aspergillosis

Investigations in mice have demonstrated that Aspergillus flavus is more virulent than all other Aspergillus species except A. tamari. However, there is a complete lack of information on the immune responses elicited by A. flavus in systemic model. This communication reports the progression of infection and cytokine profile in BALB/c mice in response to intravenous challenge of A. flavus. The pathogenesis of infection was evaluated morphologically and by the analysis of Colony Forming Units (CFUs) in kidney homogenates. The kinetics of regulated cytokines was determined in kidneys by cytokine-specific murine ELISA. During the initial phase of infection the rate of clearance of A. flavus was high, most likely through recruited neutrophils and the resident renal macrophages with concurrent significant release of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-12/IL-23p40, IL-6) indicating antifungal innate immune response to be active at the site. However, at 24 h PI there was a significant rise of IL-17 and IL-23 suggesting the activation of IL-17/IL-23 axis of inflammation resulting in rise of CFU. The lack of significant induction in the anti-inflammatory cytokines like IL-4 and IL-10 confirmed the absence of Th2 type of response. In the late phase, after 3 days post-infection, there was a rise in the number of pathogen in the kidneys as determined by histopathology and CFU counts. The A. flavus hyphae were evident in the renal pelvis and ureter and we propose the production of blastoconidia by metamorphosed hyphae.