Possible Association between Suicide Committed under Influence of Ethanol and a Variant in the AUTS2 Gene

Background

rs6943555 in AUTS2 has been shown to modulate ethanol consumption. We hypothesized that rs6943555 might be associated with completed suicide.

Methods

We genotyped rs6943555 in 625 completed suicides and 3861 controls using real-time TaqMan Allelic Discrimination Assay. All individuals were Polish Caucasians.

Results

We detected an association between suicide and rs6943555 A allele (OR = 1.17, P = 0.018 for allelic comparison, OR = 1.24, P = 0.013 for dominant, and OR = 1.18, P = 0.020 for co-dominant model of inheritance). The association remained significant after adjusting for age and gender (co-dominant: P = 0.002 and dominant model: P = 0.001). After stratifying suicides according to blood ethanol concentration (BAC≤ 20 mg/dl and BAC > 20 mg/dl) the association remained significant only for cases who committed suicide under influence of alcohol (co-dominant: OR  =  1.37, P = 0.004 and dominant model: OR = 1.45, P = 0.006). To validate this finding we genotyped another cohort of 132 cases. We reproduced the association between rs6943555 A allele and suicide under influence of ethanol (allelic comparison: OR = 1.55, P = 0.023; co-dominant : OR = 1.54, P = 0.031; dominant model: OR = 1.84, P = 0.015). Analyzing pooled suicides with BAC >20 mg/dl (N = 300) we found the association of rs6943555 A allele not only vs. controls (allelic OR = 1.41, P = 0.00029) but also vs. cases with BAC ≤ 20 mg/dl (N = 449, allelic OR = 1.33, P = 0.019).

Conclusions

In our study rs6943555 A allele is associated with suicide committed after drinking ethanol shortly before death. The rs6943555 A allele may be linked to adverse emotional reaction to ethanol, which could explain the association with lower consumption in general population as well as the predisposition to suicide under influence of ethanol.     

Properties of monocytes generated from haematopoietic CD34+ stem cells from bone marrow of colon cancer patients

Monocytes exhibit direct and indirect antitumour activities and may be potentially useful for various forms of adoptive cellular immunotherapy of cancer. However, blood is a limited source of them. This study explored whether monocytes can be obtained from bone marrow haematopoietic CD34⁺ stem cells of colon cancer patients, using previously described protocol of expansion and differentiation to monocytes of cord blood-derived CD34⁺ haematopoietic progenitors. Data show that in two-step cultures, the yield of cells was increased approximately 200-fold, and among these cells, up to 60 % of CD14⁺ monocytes were found. They consisted of two subpopulations: CD14⁺⁺CD16⁺ and CD14⁺CD16^?, at approximately 1:1 ratio, that differed in HLA-DR expression, being higher on the former. No differences in expression of costimulatory molecules were observed, as CD80 was not detected, while CD86 expression was comparable. These CD14⁺ monocytes showed the ability to present recall antigens (PPD, Candida albicans) and neoantigens expressed on tumour cells and tumour-derived microvesicles (TMV) to autologous CD3⁺ T cells isolated from the peripheral blood. Monocytes also efficiently presented the immunodominant HER-2/neu_369–377 peptide (KIFGSLAFL), resulting in the generation of specific cytotoxic CD8⁺ T lymphocytes (CTL). The CD14⁺⁺CD16⁺ subset exhibited enhanced cytotoxicity, though nonsignificant, towards tumour cells in vitro. These observations indicate that generation of monocytes from CD34⁺ stem cells of cancer patients is feasible. To our knowledge, it is the first demonstration of such approach that may open a way to obtain autologous monocytes for alternative forms of adaptive and adoptive cellular immunotherapy of cancer.     

Mesenchymal stem cells contribute to endogenous FVIII:c production

Besides the liver, it has been difficult to identify which organ(s) and/or cellular component(s) contribute significantly to the production of human FVIII:c (FVIII). Thus far, only endothelial cells have been shown to constitute a robust extrahepatic source of FVIII, possibly explaining both the diverse presence of FVIII mRNA in the body, and the observed increase in FVIII levels during liver failure. Here, we investigate whether human mesenchymal stem cells (MSC), ubiquitously present in different organs, could also contribute to FVIII production. MSC isolated from human lung, liver, brain, and bone marrow expressed FVIII message as determined by quantitative‐RT‐PCR. Using an antibody specific for FVIII, confocal microscopy, and umbilical cord‐derived endothelial cells (HUVEC) as a negative control, we demonstrated that, in MSC, FVIII protein was not stored in granules; rather, it localized to the perinuclear region. Furthermore, functional FVIII was detected in MSC supernatants and cell lysates by aPTT and chromogenic assays. These results demonstrate that MSC can contribute at low levels to the functional FVIII pool, and advance the understanding of the physiology of FVIII production and secretion. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.     

From spring sources to springbrook: Changes in environmental characteristics and benthic fauna

Spatial patterns in macroinvertebrate communities and some abiotic factors were examined in three rheocrene springs and their springbrooks (Kraków-Cz?stochowa Upland, southern Poland). The mean discharge of particular springs ranged from 5 to 11 L s^?1, and its annual fluctuations were small. Water temperature was very stable at all sampling sites. In the eucrenon the number of benthic taxa was the smallest (9–14 determined to the family level), but the densities were the highest (approx. 14000 ind. m^?2). The biggest changes in macroinvertebrate composition were observed in the modified hypocrenon, which is an artificial pond. The lowest number of taxa were found in a natural, short springbrook with a nondiversified bottom substrate. The density of crenophilic taxa (Drusus trifidus, Dugesia gonocephala, Elmidae) diminished along the springbrooks, while the opposite trend was observed for ubiquitous taxa (some Oligochaeta, Asellus aquaticus and Chironomidae). Even in a very short natural springbrook (30 m), Drusus trifidus, the only species of Trichoptera found in the springs discussed here, goes through the entire development cycle. The strongest influence of a big river was observed at the outflow of one of the natural springbrooks, where the highest number of riverine oligochaete species were found. The benthic fauna of the springs studied here differed from that found in other springs in this area — the absence of the typical crenophilic species Bithynella austriaca (Gastropoda) and the presence of Gianus aquedulcis (Oligochaeta) may indicate the autonomy of the spring fauna in the Mstów area, possibly resulting from the postglacial geomorphological formation of this region or differences in habitat conditions.     

Interpretation of the invertebrate-based BMWP-PL index in a gravel-bed river: insight from the Polish Carpathians

Like its British prototype (Biological Monitoring Working Party score system), the Polish benthic invertebrate-based BMWP-PL index is commonly regarded as an indicator of river water quality. This interpretation of the index has been verified in a study of the gravel-bed Bia?a River. Benthic macroinvertebrates were sampled at 10 sites and compared in one channelized and one unmanaged cross-section per site. The resulting taxa richness and BMWP-PL index scores were compared with water quality and physical habitat characteristics in the cross-sections. Channelized and unmanaged cross-sections clearly differed in their physical habitat conditions, and water quality characteristics mostly varied in the downstream direction. Particular cross-sections hosted between 3 and 26 invertebrate taxa, with the respective BMWP-PL scores indicating the water in the surveyed cross-sections varied between high and poor quality. However, the BMWP-PL scores were unrelated to physicochemical characteristics of the river water, which consistently pointed to high water quality. Instead, the scores were significantly related to several physical habitat variables, with the number of low-flow channels in a cross-section explaining the largest proportion of the variance in the index values. The relationship of the scores with the complexity of flow pattern in the river and a lack of their dependence on physicochemical water characteristics show that the BMWP-PL index should not be regarded as an indicator of water quality but rather as an indicator of the ecological status of rivers, dependent both on their hydromorphological and water-quality characteristics.     

Search for new tools to combat Gram-negative resistant bacteria among amine derivatives of 5-arylidenehydantoin

A series of amine-alkyl derivatives of 5-arylidenehydantoin 3–21 was evaluated for their ability to improve antibiotic effectiveness in two strains of Gram-negative Enterobacter aerogenes: the reference strain (ATCC-13048) and the chloramphenicol-resistant derivative over-producing the AcrAB-TolC efflux pump (CM-64). Three antibiotics, chloramphenicol, nalidixic acid and sparfloxacin were used as markers of efflux pump activity. New compounds (5–16) were obtained within 3–4 step synthesis using Knoevenagel condensation, Mitsunobu reaction and microwave aided N-alkylation. Molecular modeling based structure–activity relationship (SAR) studies were performed. The most active compounds: (Z)-5-(4-(diethylamino)benzylidene)-3-(2-hydroxy-3-(4-(2-hydroxyethyl)piperazin-1-yl)propyl)imidazolidine-2,4-dione (14) and (Z)-5-(2,4-dimethoxybenzylidene)-3-(2-hydroxy-3-(isopropylamino)propyl)imidazolidine-2,4-dione (15) induced fourfold decrease of minimal inhibition concentration (MIC) of all tested antibiotics in the strain CM-64 overexpressing the AcrAB-TolC pump.     

The role of l-arginine-nitric oxide pathway in bacterial translocation

This study investigated the nitric oxide (NO) role as a mediator of arginine on bacterial translocation (BT) and gut damage in mice after intestinal obstruction (IO). The effects of pretreatment with arginine with or without NO inhibition on the systemic and local immunological response were also assessed. Mice were categorized into four groups. Group ARG received chow containing 2 % arginine, while group ARG + l-NAME received the same diet plus l-NAME (N-nitro-l-arginine methyl ester) by gavage. The IO and Sham groups were fed standard chow. After 7 days, animals were gavaged with radiolabeled Escherichia coli, anesthetized and subjected to IO, except the Sham group. Animals were euthanized after 18 h, and BT was evaluated in the mesenteric lymph nodes, blood, liver, spleen and lungs. In another experiment, the intestinal injury was assessed regarding intestinal permeability and ileum histological analyses. Intestinal secretory immunoglobulin A (sIgA) levels, serum IFN-γ and IL-10 cytokines were assessed. Arginine reduced BT, but NO inhibition enhanced BT compared with the ARG group (p < 0.05). Intestinal permeability in the ARG and ARG + l-NAME groups was similar but decreased when compared with the IO group (p < 0.05). Histological preservation was observed. Arginine treatment increased IL-10 and sIgA levels when compared with the Sham and IO groups (p < 0.05). The cytokines and sIgA concentrations were similar in the ARG + l-NAME and Sham groups. Arginine appeared to reduce BT and its effects on the modulation of cytokines and secretory IgA in mice after IO are mediated by NO production.     

Redox signals as a language of interorganellar communication in plant cells

Plants are redox systems and redox-active compounds control and regulate all aspects of their life. Recent studies have shown that changes in reactive oxygen species (ROS) concentration mediated by enzymatic and non-enzymatic antioxidants are transferred into redox signals used by plants to activate various physiological responses. An overview of the main antioxidants and redox signaling in plant cells is presented. In this review, the biological effects of ROS and related redox signals are discussed in the context of acclimation to changing environmental conditions. Special attention is paid to the role of thiol/disulfide exchange via thioredoxins (Trxs), glutaredoxins (Grxs) and peroxiredoxins (Prxs) in the redox regulatory network. In plants, chloroplasts and mitochondria occupying a chloroplasts and mitochondria play key roles in cellular metabolism as well as in redox regulation and signaling. The integrated redox functions of these organelles are discussed with emphasis on the importance of the chloroplast and mitochondrion to the nucleus retrograde signaling in acclimatory and stress response.