Optimization of the photodynamic inactivation of prions by a phthalocyanine photosensitizer: The crucial involvement of singlet oxygen

Prion disorders are fatal neurodegenerative diseases caused by the autocatalytic conversion of a natively occurring prion protein (PrP^C) into its misfolded infectious form (PrP^TSE). The proven resistance of PrP^TSE to common disinfection procedures increases the risk of prion transmission in medical settings. Herein, we present the effective photodynamic inactivation (PDI) of prions by disulfonated hydroxyaluminum phthalocyanine (AlPcOH(SO₃)₂) utilizing two custom‐built red light sources. The treatment eliminates PrP^TSE signal in infectious mouse brain homogenate with efficiency that depends on light intensity but has a low effect on the overall protein content. Importantly, singlet oxygen (O₂(¹Δ_g)) is the only species significantly photogenerated by AlPcOH(SO₃)₂, and it is responsible for the PDI of prions. More intensive light conditions show not only higher O₂(¹Δ_g) production but also decreases in AlPcOH(SO₃)₂ photostability. Our findings suggest that PDI by AlPcOH(SO₃)₂‐generated O₂(¹Δ_g) represents a promising approach for prion inactivation that may be useful in future decontamination strategies for delicate medical tools.     

Arsenic metabolism in multiple myeloma and astrocytoma cells

Arsenic trioxide (As2O3, Trisenox) is used to treat patients with refractory or relapsed acute promyelocytic leukemia (APL). Its ability to induce apoptosis in various malignant cell lines has made it a potential treatment agent for other malignancies and many clinical trials are currently in progress to evaluate its clinical usefulness for multiple myeloma and glioblastoma cancer. In the present study, we investigated the metabolism of As2O3 regarding its cellular biotransformation and interaction with metallothionein (MT) as a possible protective responses of cells to arsenic-induced cytotoxicity. The study was performed on two types of cell treated with As2O3: (1) human astrocytoma (glioblastoma) cell line U87MG treated with 0.6 microM arsenic for 0, 3, 12, 24, and 48 h or 12 microM arsenic for 3, 6, 12, 24, and 48 h and (2) bone marrow cells (BM) from two patients with multiple myeloma (MM) treated with 7 microM arsenic for 0, 43, and 67 h. Cotreatment with vitamin C (1 mg/mL) was tested in longer exposure of MM BM cells. Traces of methylation products (mainly monomethylarsenic acid) were detected in cell lysates of both cell types and in pellets of U87 MG cells, although we found problems with column-sample interactions in cases where methanol pretreatment of the sample was not used. Pentavalent inorganic arsenic (AsV) was identified in both cell types, and up to 80% of total As in MM bone marrow cell lysates was present as AsV. Such an occurrence (generation) of pentavalent arsenic after As2O3 treatment demonstrates the presence of biological oxidation of trivalent arsenic, which could represent an additional protective mechanism of the cell. Vitamin C decreased As cell content and increased the percentage of pentavalent inorganic arsenic (in the growth medium and cells). The presence of metallothionein (MT) and its response to arsenic treatment was checked in all U87 MG cells, in the control, and in one exposed sample of MM BM cells. During 48 h exposure to 0.6 or 12 muM arsenic MTI/II levels increased in U87 MG cells, but with variable Zn levels, increased Cu levels, and As binding observed in traces only. Involvement of the MT-III isoform was negligible. In contrast, 43 h exposure to 7 microMarsenic did not increase MT content in multiple myeloma cells, and the levels even decreased with respect to the control. To evaluate the importance of the observed processes, MTs in U87 and AsIII-AsV conversion in MM BM cells, which could represent a resistance response of cancer cells treated by As2O3, longer-term observation with different arsenic concentrations should be performed.     

Personality,Attentional Biases towards Emotional Faces and Symptoms of Mental Disorders in an Adolescent Sample

Objective

To investigate the role of personality factors and attentional biases towards emotional faces, in establishing concurrent and prospective risk for mental disorder diagnosis in adolescence.

Method

Data were obtained as part of the IMAGEN study, conducted across 8 European sites, with a community sample of 2257 adolescents. At 14 years, participants completed an emotional variant of the dot-probe task, as well two personality measures, namely the Substance Use Risk Profile Scale and the revised NEO Personality Inventory. At 14 and 16 years, participants and their parents were interviewed to determine symptoms of mental disorders.

Results

Personality traits were general and specific risk indicators for mental disorders at 14 years. Increased specificity was obtained when investigating the likelihood of mental disorders over a 2-year period, with the Substance Use Risk Profile Scale showing incremental validity over the NEO Personality Inventory. Attentional biases to emotional faces did not characterise or predict mental disorders examined in the current sample.

Discussion

Personality traits can indicate concurrent and prospective risk for mental disorders in a community youth sample, and identify at-risk youth beyond the impact of baseline symptoms. This study does not support the hypothesis that attentional biases mediate the relationship between personality and psychopathology in a community sample. Task and sample characteristics that contribute to differing results among studies are discussed.     

Ecological differentiation of Central EuropeanBolboschoenus taxa and their relationship to plant communities

The taxa of theBolboschoenus maritimus group occurring in Central Europe were studied with respect to morphological differentiation, plant communities and soil conditions. Four morphological types ofBolboschoenus were distinguished, differing in habitat conditions, dispersal and distribution: type 1 —Bolboschoenus maritimus subsp.maritimus with narrow triangular fruits; type 2 —B. maritimus subsp.maritimus with wider triangular fruits, type 3 —B. maritimus subsp.compactus with round convex fruits; and type 4 —B. planiculmis auct. with concave fruits. Strong ecological differentiation of these types was found compared with relatively weak morphological diagnostic features. High discriminant efficiency appeared in the relationship to soil chemistry. Differences were also found in habitat-type spectra of individualBolboschoenus morphological types, which was reflected in their affinities to plant communities. Nomenclature, taxonomic classification, and distribution of these taxa in Europe need thorough revision.     

A Genealogical Study of Essential Hypertension with and without Obesity in French Canadians

Objectives: To investigate genetic homogeneity in a set of hypertensive families and in subsets chosen for high and low prevalence of obesity; and to compare fasting insulin and lipids, ion transport, and water homeostasis in the obese and lean families. Research Methods and Procedures: The study was carried out in a relative population isolate of the Saguenay/Lac St. Jean region in Canada. Genetic homogeneity was evaluated with the mean coeffigcients of kinship (φ) and inbreeding (F) computed with ascending genealogies. Serum insulin and lipids were measured after overnight fasting. Total body water was estimated with bioelectrical impedance. Sodium‐lithium countertransport and sodium‐potassium co‐transport were determined in freshly isolated erythrocytes. Results: F and φ were increased in hypertensive families compared with families selected at random. F and φ were further increased within the subsets of obese and lean families. In addition, fasting insulin, total body water, sodium‐lithium countertransport, and sodium‐potassium co‐transport were higher in the obese than in the lean families. The two subsets of families did not differ by fasting lipids. Discussion: In the Saguenay/Lac St. Jean population, the degree of genetic homogeneity was increased in families selected for hypertension, and it was further increased in subsets of hypertensive families with high and low prevalence of obesity. This suggests that hypertension in lean and obese individuals may represent, at least in part, separate genetic entities. Some of the extra genes shared in common within the subsets may contribute to their differences in body weight, insulin sensitivity, ion transport, and water homeostasis.