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Background: The gut microbiota impacts on central nervous system (CNS) function via the microbiota-gut-brain axis. Thus, therapeutics targeting the gut microbiota such as probiotics have the potential for improving mental health. This meta-analysis synthesizes the evidence regarding the impacts of probiotics on psychological well-being, psychiatric symptoms and CNS functioning., Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were applied for executing this review using the databases PubMed, Web of Science and Cochrane Library. The data were summarized at qualitative and quantitative level., Results: Fifty-four randomized placebo-controlled studies were included, of which 30 were eligible for meta-analysis. If investigated, the probiotics mostly exerted effects on CNS function. Most probiotics did not affect mood, stress, anxiety, depression and psychiatric distress when compared to placebo at the qualitative level. At quantitative level, depression and psychiatric distress improved slightly in the probiotic condition (depression: mean difference -0.37 (95% CI: -0.55, -0.20); p ≤ 0.0001; psychiatric distress: mean difference -0.33 (95% CI: -0.53, -0.13); p = 0.001)., Conclusions: To date it is unclear to which extent and in which specific areas next generation probiotics selected and developed for their ability to improve psychiatric condition and potentially other CNS functions are promising.

Background: Functional gastrointestinal disorders such as irritable bowel syndrome (IBS) report clinical improvement following probiotic therapy, but whether psychiatric comorbidity and quality-of-life in IBS improves directly or in directly is unknown. This meta-analysis synthesized the evidence regarding the effects of probiotics on quality of life (QoL), anxiety and depression in IBS., Methods: The review was executed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the databases PubMed, Web of Science and Cochrane Library. For QoL, the data were meta-analyzed, and for anxiety and depression a qualitative analysis was performed., Results: Thirty-five placebo-controlled studies were included of which 11 were eligible for meta-analysis. QoL improved with probiotic and placebo similarly, with the probiotic interventions slightly superior (mean QoL difference-0.36 (95% CI: 0.07, 0.64); p = 0.01). Anxiety and depression were similar between placebo and probiotic groups following therapy., Conclusion: For IBS, probiotic therapy improved QoL, but had no effects on anxiety and depression. However, the applied probiotics were not developed for selective effects on psyche and the brain. Therefore, it remains to be shown whether or not patients with IBS would benefit from second generation probiotics developed for these central effects (psychobiotics).

In apple, the first-order branch of a tree has a characteristic architecture constituting three shoot types: bourses (rosettes), bourse shoots, and vegetative shoots. Its overall architecture as well as that of each shoot thus determines the distribution of sources (leaves) and sinks (fruits) and could have an influence on the amount of sugar allocated to fruits. Knowledge of architecture, in particular the position and area of leaves helps to quantify source strength. In order to reconstruct this initial architecture, rules equipped with allometric relations could be used: these allow predicting model parameters that are difficult to measure from simple traits that can be determined easily, non-destructively and directly in the orchard. Once such allometric relations are established they can be used routinely to recreate initial structures. Models based on allometric relations have been established in this study in order to predict the leaf areas of the three different shoot types of three apple cultivars with different branch architectures: "Fuji," "Ariane," and "Rome Beauty." The allometric relations derived from experimental data allowed us to model the total shoot leaf area as well as the individual leaf area for each leaf rank, for each shoot type and each genotype. This was achieved using two easily measurable input variables: total leaf number per shoot and the length of the biggest leaf on the shoot. The models were tested using a different data set, and they were able to accurately predict leaf area of all shoot types and genotypes. Additional focus on internode lengths on spurs contributed to refine the models.

Biolignin, a wheat straw lignin produced by acetic acid/formic acid/water hydrolysis, was characterized by (31)P and (13)C-(1)H 2D NMR spectroscopy and by size-exclusion chromatography. Biolignin is a mixture of low molar mass compounds (Mn = 1660 g/mol) made up of S, G, and H units and of coumaric and ferulic acid units. β-5 and β-O-4 interunit linkages are partially acylated in the γ-position by acetate and p-coumarate groups. Deacylated samples with a low content of contaminants were obtained by combining alkaline hydrolysis and solvent extraction. The high phenolic OH content found by (31)P NMR reflects the presence of condensed aromatic units, such as 5-5 units. Reaction of purified lignin with ethanol and ethane-1,2-diol yielded esterified lignins much more soluble than Biolignin in common organic solvents. During this reaction, the secondary OH of β-O-4 linkages was simultaneously etherified. Phenol hydroxyethylation by 2-chloroethanol yielded samples containing only aliphatic hydroxyl groups.

This Letter reports the synthesis and characterization of a new series of water-stable and soluble photosensitizers (PS-CNCs) composed of cellulose nanocrystals (CNCs) bearing polyaminated chlorin p6. With a view to improve cancer cell targeting, these photosensitizers were assayed for their antitumor activity against HaCat cell line. IC(50) values fell within the nanomolar-range, making these photosensitizers promising for further in vitro and in vivo investigations., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A series of polyamine-porphyrin conjugates bearing two (cis or trans position) or four units of spermidine or spermine was synthesized. We studied the binding of these cationic porphyrins to calf thymus DNA by the means of UV-vis spectroscopy and we investigated their ability to cleave plasmid DNA in the presence of light. DNA binding and DNA photocleavage abilities were found to depend on structural characteristics as (a) the relative positions of the side chains on the porphyrin ring and (b) the nature of the attached side chains (spermidine or spermine). DNA cleavage was also studied in the presence of a singlet oxygen quencher (NaN(3)) and in the presence of a hydroxyl radical scavenger (mannitol). Singlet oxygen was the major species responsible for the cleavage of DNA previously observed. Collectively, these data show that polyamine-porphyrin conjugates could be promising phototherapeutic agents.

Allelic exclusion of IgH chain expression is stringently established before or during early B cell maturation. It likely relies both on cellular mechanisms, selecting those cells in which a single receptor allows the best possible Ag response, and on molecular restrictions of gene accessibility to rearrangement. The extent to which transcriptional control may be involved is unclear. Transcripts arising from nonfunctional alleles would undergo nonsense-mediated degradation and their virtual absence in mature cells cannot ensure that transcription per se is down-regulated. By contrast, somatic hypermutation may provide an estimate of primary transcription in Ag-activated cells since both processes are directly correlated. For coding regions, the rate and nature of mutations also depend upon Ag binding constraints. By sequencing intronic sequence downstream mouse VDJ genes, we could show in the absence of such constraints that somatic hypermutation intrinsically targets nonfunctional rearranged alleles at a frequency approaching that of functional alleles, suggesting that transcription also proceeds on both alleles at a similar rate. By contrast and confirming the strong dependency of somatic hypermutation upon transcription, we show that artificial blockade of transcription on the nonfunctional allele by a knock-in neomycin resistance cassette keeps the VDJ region unmutated even when its promoter is intact and when it is fully rearranged.

Four transcriptional enhancers lie downstream of the immunoglobulin heavy chain locus: Calpha3'/hs3a, hs1,2, hs3b, and hs4. Although individually weak, these elements have strong transcriptional synergies when combined and they altogether behave as a locus control region. Previous knockout experiments in the 3' region have shown that both hs3a and hs1,2 are dispensable for normal expression and rearrangement of the IgH locus but that their replacement with a transcribed neo gene severely affects class switch recombination. Here we show that even in the absence of a neo gene, joint deletion of the last two 3' enhancers, hs3b and hs4, severely impairs germline transcription and class switching to most isotypes and may in addition affect mu gene expression in resting B cells.

We studied the hs1,2 transcriptional enhancer identified downstream of the human alpha1 gene of the immunoglobulin H (IgH) locus, for which two different allelic configurations (a and b) were previously reported by Southern blotting. By using a polymerase chain reaction (PCR) method we amplified minisatellites within the hs1,2 core enhancer, with variable numbers of tandem repeats (VNTR) defining three 'PCR alleles' alpha1A, alpha1B and alpha1C (including one, two and three repeats, respectively). Five different alpha1 h1,2 genotypes were encountered in a population of 513 donors, representing 13.8, 34.5, 49.7, 1.3 and 0.6% for the AA, BB, AB, AC and BC genotypes, respectively. Luciferase assays showed that increasing the number of minisatellites increased the transcriptional strength of the alpha1 hs1,2 enhancer. Simultaneous determination of Southern blot alleles and VNTR alleles only showed a partial linkage between both types of polymorphism, altogether defining at least six different allelic forms of the 3'alpha1 region. In conclusion, the present study further demonstrates the genetic instability of the 3'alpha region, for which multiple alleles have been generated through inversions and internal deletions and/or duplications. This study also strengthens the hypothesis that the polymorphism at the IgH 3' regulatory region of the alpha1 gene could play a role in the outcome of diseases involving immunoglobulin secretion.

The lower avidity and/or affinity of antibodies generated by an aged immune system could be attributed to two major changes in the antibody repertoire: a shift in germline gene usage and a decrease in the rate of immunoglobulin hypermutation. In an attempt to identify the mechanisms involved in the observed humoral immune deficiency in the elderly, we studied whether differences in the somatic diversity of a particular Vkappa region occurred with ageing. By using the polymerase chain reaction and sequencing, we analysed and compared Vkappa4-Jkappa rearrangements isolated from young (mean age 21 years) and aged (mean age 83 years) healthy adults. Mutations in the Vkappa4 gene compared with the germline sequence were determined as well as the length and structure of the CDR3 sequence. We analysed in detail various mechanisms contributing to CDR3 and Vkappa variability in rearrangements involving the Vkappa4 gene. Our data revealed that, despite strong individual variations, significantly lower levels of somatic mutation were found in the aged group, both for complementarity-determining regions (CDRs) and framework regions (FRs) encoding Vkappa4 sequences. This decrease mostly affected mutations responsible for replacements and thus resulted in a lowered somatic diversification of the encoded Vkappa4 proteins in aged individuals. Moreover, comparison of the CDR3 regions of the Vkappa4-Ckappa cDNA revealed changes in light-chain junctional diversity that correlated with age. Altogether these data suggest an impaired light-chain somatic diversity in connection with human senescence.

Immunosenescence involves modifications of humoral and cellular immunity. Here we report the analysis of human leukocyte antigen (HLA) expression on T lymphocytes, B lymphocytes and monocytes of 58 healthy subjects aged 23-95 years old. Using a double staining immunofluorescence and flow cytometry analysis, we have determined the percentages of cells expressing HLA class-I and HLA-DR antigens. The number of antigenic sites expressed per cell were evaluated for HLA-ABCw, HLA-A, HLA-B, HLA-DR locus with a flow cytometry quantification technique. With advancing age, we observed: (i) a significant decrease of the percentage of T cells and B cells expressing HLA-A products; (ii) a decrease of the number of HLA class-I antigenic sites expressed per cell on the three populations tested, predominantly on B cells and in a locus-dependent fashion; (iii) a decrease of the number of HLA-DR molecules expressed per T cell, although the percentage of T cells expressing DR products was increased; (iv) a significant diminution of the percentage of B cells expressing HLA-DR molecules, without changes of the number of HLA-DR antigenic sites per cells. These changes in HLA expression with increasing age could contribute to the decreased level of immunologic responsiveness observed with ageing and contribute to the modification of antigen recognition.

The susceptibility of fish to disease is partly dependent on their environment, in particular on water temperature. It is generally accepted that lower temperatures adversely affect specific immune responses mediated by T helper cells. The probable mechanisms involved in such suppression in teleost fish are reviewed. Furthermore, the effects of temperature on nonspecific defences, such as phagocytosis and cytotoxicity, are described and total immune competence in teleosts at low environmental temperatures is discussed.

The effect of environmental temperatures on immune competence was investigated in carp which were subjected to changes in water temperature. The activity of non-specific cytotoxic cells (NCC) against P815 target cells, and the anti-DNP antibody response were evaluated until day 56 after transfer. Low environmental temperature (12 +/- 0.5 degrees C) enhanced NCC activity and decreased antibody production. In contrast a high environmental temperature (28 +/- 0.5 degrees C) was without effect on these parameters when compared to the standard temperature (20 +/- 0.5 degrees C). The results showed a maximum effect of low environmental temperature on day 28 and an adaptation in these immune responses 56 days following transfer. Collectively, the results indicated that non-specific immunity tends to offset specific immune suppression at low environmental temperatures. To determine the mechanism(s) by which environmental temperature affects cellular immune function, membrane fluidity measurements and sialic acid titration, as well as stress assessment by plasma cortisol measurement, were determined on day 28. Taken together, the results revealed a direct effect of temperature on cellular immune function which is modulated by membrane fluidity and sugar concentration and not by stress induction.

The effect of environmental temperature on immune competence was investigated in carp subjected to abrupt changes in water temperature. The activity of nonspecific cytotoxic cells (NCC) against P815 target cells and the lymphoproliferation induced by PHA and ConA were evaluated. Low in vivo temperature (12 +/- 0.5 degrees C) enhances NCC activity and decreases the mitogen effect of PHA, respectively; by contrast high in vivo temperature (28 +/- 0.5 degrees C) is without effect on these parameters as compared to the standard temperature (20 +/- 0.5 degrees C). The stress induced by environmental temperature variation was evaluated by plasmatic cortisol measurement. Results indicate a significant increase (p < 0.05) of cortisol levels 2 hours after transfer at low but not at high temperature as compared to the standard thermic control (60.96 +/- 17.08 vs. 16.74 +/- 4.32 ng/mL, respectively). Because only approximately 20 minutes are required before carp body and environmental temperatures are identical, the same experiments were reproduced in vitro. Results show trends similar to those found in vivo. Taken together, these data reveal a direct effect of temperature on immune cellular functions and indicate that nonspecific immunity tends to offset specific immune suppression at low environmental temperature.