Maternal telomere length inheritance in the king penguin.

Telomeres are emerging as a biomarker for ageing and survival, and are likely important in shaping life-history trade-offs. In particular, telomere length with which one starts in life has been linked to lifelong survival, suggesting that early telomere dynamics are somehow related to life-history trajectories. This result highlights the importance of determining the extent to which telomere length is inherited, as a crucial factor determining early life telomere length. Given the scarcity of species for which telomere length inheritance has been studied, it is pressing to assess the generality of telomere length inheritance patterns. Further, information on how this pattern changes over the course of growth in individuals living under natural conditions should provide some insight on the extent to which environmental constraints also shape telomere dynamics. To fill this gap partly, we followed telomere inheritance in a population of king penguins (Aptenodytes patagonicus). We tested for paternal and maternal influence on chick initial telomere length (10 days old after hatching), and how these relationships changed with chick age (at 70, 200 and 300 days old). Based on a correlative approach, offspring telomere length was positively associated with maternal telomere length early in life (at 10 days old). However, this relationship was not significant at older ages. These data suggest that telomere length in birds is maternally inherited. Nonetheless, the influence of environmental conditions during growth remained an important factor shaping telomere length, as the maternal link disappeared with chicks' age.

Molecular genetic analysis of bilateral ovarian germ cell tumors.

BACKGROUND: Ovarian germ cell tumors (oGCTs) are rare and highly heterogeneous with regard to their clinical and histologic appearance. The risk of tumor development is higher in children with aberrant sexual differentiation. Development of gonadoblastomas is seen in young women with 46,XY gonadal dysgenesis. At least 50 % of gonadoblastomas may develop into malignant oGCTs, mostly dysgerminomas. In this study, we evaluated bilateral oGCTs in clinically inapparent patients for sex chromosomal aberrations. PATIENTS AND METHODS: We analyzed tumor samples of 15 patients with synchronous bilateral oGCTs enrolled onto the consecutive MAKEI trials for non-testicular GCTs. Paraffin embedded samples from the Kiel German Childhood Tumor Registry were evaluated for the presence of Y-chromosomal sequences. Molecular genetic techniques included comparative genomic hybridization, polymerase chain reaction, and fluorescence in situ hybridization. RESULTS: Among 15 patients with bilateral oGCTs, Y-chromosomal DNA sequences were detected in 6 tumors. Both mature teratomas were negative for Y-chromosomal DNA. Thus, 5 of 12 malignant oGCTs and 1 immature teratoma (with elevated AFP) showed Y-chromosomal material. A 45(X,0) karyotype could not be demonstrated. CONCLUSIONS: These investigations provide additional insight into the development of oGCTs: mature teratomas, which develop from postmeiotic germ cells, are not associated with gonadal dysgenesis. Bilateral immature teratomas, dysgerminomas and mixed malignant oGCTs may frequently show Y-chromosomal DNA, indicating underlying but clinically inapparent gonadal dysgenesis. Thus, the presence of aberrant Y-chromosomal sequences appears to be involved in tumor development in about half of these patients.

Interferon-α stimulates TRAIL expression in human keratinocytes and peripheral blood mononuclear cells: implications for the pathogenesis of cutaneous lupus erythematosus.

BACKGROUND: The tumour necrosis factor-related apoptosis-inducing ligand TRAIL has been shown to participate in the pathogenesis of systemic lupus erythematosus (SLE). The accumulation of apoptotic cell debris has been hypothesized to induce this autoimmune inflammation, and TRAIL may trigger this programmed cell death. Furthermore, TRAIL is among the interferon (IFN)-regulated genes which are typically expressed in the peripheral blood of patients with acute SLE. OBJECTIVES: As an inappropriate activation of the type I IFN system plays an important role in both SLE and cutaneous lupus erythematosus (CLE) subsets, we hypothesized that TRAIL might also participate in the pathogenesis of CLE. METHODS: Immunohistochemistry and immunofluorescence analyses were used to identify and localize TRAIL-expressing cells in CLE skin specimens. TRAIL expression in peripheral blood mononuclear cells (PBMC) isolated from patients with CLE was measured by flow cytometry. The impact of IFN-α treatment on TRAIL expression by keratinocytes and PBMC was evaluated by reverse transcription-polymerase chain reaction and flow cytometry. RESULTS: Keratinocytes are beside CD11c+ and BDCA2+ dendritic cells the major TRAIL-expressing cells in CLE lesions. TRAIL is upregulated on the surface of circulating CD11c+ PBMC isolated from patients with CLE. Treatment of keratinocytes and PBMC with recombinant IFN-α strongly enhances TRAIL expression by these cells. The proapoptotic TRAIL receptor R1 is expressed by keratinocytes in CLE skin lesions. CONCLUSIONS: TRAIL is strongly expressed in the skin and the blood of patients with CLE and may trigger the apoptotic death of kerationcytes in CLE via the TRAIL receptor R1. An IFN-α-induced TRAIL expression may in this way participate in the pathogenesis of CLE.

Enhanced CCR5+/CCR3+ T helper cell ratio in patients with active cutaneous lupus erythematosus.

Cutaneous lupus erythematosus (CLE) is characterized by enhanced interferon α (IFNα) levels in serum and in tissue. Since IFNα promotes a Th1-biased immune response, we hypothesized that a Th1-associated chemokine receptor profile should be a typical finding in patients with active CLE. Therefore, peripheral blood mononuclear cells were isolated from patients with different CLE subsets (n = 15), healthy controls (n = 13) and patients under immunotherapy with IFNα (n = 7). T helper cells were analysed by flow cytometry for the expression of the chemokines receptor CCR5, indicative for Th1 cells, and of CCR3, indicating Th2. In addition, intracellular levels of the type I IFN-inducible MxA protein were measured. Patients with widespread active CLE skin lesions had a significantly increased expression of CCR5, whereas expression of CCR3 was decreased when compared with healthy controls. MxA expression was significantly enhanced in all investigated CLE subtypes, with the highest levels in patients with widespread skin lesions. The enhanced CCR5/CCR3 ratio closely correlated with the MxA levels in peripheral lymphocytes and with disease activity. Our analyses revealed that active CLE is associated with a systemic type I IFN effect that appears to induce a shift towards a Th1-associated chemokine receptor profile. The CCR5/CCR3 T-helper cell ratio might therefore represent an indirect marker for the disease activity in CLE.

[Internet-based approaches in the therapy of eating disorders]. / Internetbasierte Ansätze in der Therapie von Essstörungen.

Recent technological developments of communication media offer new approaches to diagnostic and therapeutic interactions with patients. One major development is Internet-based primary prevention in vulnerable individuals not yet suffering as well as the development of new therapeutic approaches for affected individuals based on the experiences of guided self-help through CD, DVD or bibliotherapy. The eating disorder literature shows several interesting, partly controlled and randomized, studies on bulimia nervosa, a few studies on binge eating disorder and no studies on anorexia nervosa. As part of the German Eating Disorder Network on Psychotherapy (EDNET) a 9-month Internet-based relapse prevention program for patients with anorexia nervosa after inpatient treatment was evaluated. Conception, first experiences and first results of the Internet-based relapse prevention program for anorexia nervosa are reported.

Pathogenesis of cutaneous lupus erythematosus: common and different features in distinct subsets.

The term 'cutaneous lupus erythematosus' (CLE) comprises several related autoimmune skin disorders, defined as 'specific' skin manifestations of lupus erythematosus (LE). The spectrum of clinical presentation of CLE is wide, reaching from mild erythema to disseminated scarring skin lesions. There is increasing knowledge concerning the pathogenesis of LE skin lesions and it has been shown that a complex network of cutaneous cytokines, chemokines and adhesion molecules orchestrate and promote tissue injury observed in LE skin lesions. However, a complete understanding of the diverse pathophysiological mechanisms in the different CLE subsets does not exist. Here we review the main pathological features described in CLE patients against the background of the clinical diversity of different CLE subtypes.

Corticosterone mediates telomere length in raptor chicks exposed to chemical mixture.

Stressors experience early in life by animals may have carry over impacts on life-traits over the life cycle. Accelerated telomere attrition induced by stress during development and growth could play a role in such delayed effects. Among stressors, exposure to chemicals may modify telomere dynamic but, to date, the trends evidenced between exposure and telomere shortening remains inconsistent. Moreover, the role of corticosterone as a possible mediator of chemical impact on telomere is not yet clearly established. Here, we investigated in wild populations of Red kite whether nestling exposure to metals and pesticides was related to corticosterone concentrations in feathers and telomere length measured in 47 individuals. Lead and mercury concentrations in blood ranged from 2.3 to 59.0 µg L-1 and to 1.4 to 115.7 µg L-1, respectively, and were below the toxicity thresholds proposed for wildlife. Rodenticides were detected in 30% of the chicks. Corticosterone increased with mercury and lead in interaction, showing a synergistic effect of these 2 non-essential metals on this stress hormone. Telomere length was not linked to metals and/or rodenticide exposure while it was related negatively to corticosterone. The relationship between telomere and corticosterone was modulated by nestling's age, which suggests that the rate of telomere shortening is higher when corticosterone increases. Our findings propose an effect of low exposure of Red Kite nestlings to mercury and lead mixture to raise baseline corticosterone in feathers. The relationships established suggest the hypothesis that telomere attrition could be an indirect consequence of metal exposure mediated by corticosterone.

Interleukin-20 plays a critical role in maintenance and development of psoriasis in the human xenograft transplantation model.

BACKGROUND: Interleukin (IL)-20 is a recently discovered cytokine displaying increased levels in psoriatic lesions. Interestingly, IL-20 levels decrease with antipsoriatic treatment, correlating with clinical improvement. However, the role of IL-20 in the aetiology of psoriasis is unknown. OBJECTIVES: In this study, we investigate the effects both of blocking IL-20 signalling in psoriatic plaques and of adding IL-20 to nonlesional psoriasis skin. METHODS: We employed the human skin xenograft transplantation model in which psoriatic plaques and nonlesional keratome skin biopsies obtained from donors with moderate to severe plaque psoriasis were transplanted on to immuno-deficient mice. The transplanted mice were treated with anti-IL-20 antibodies or recombinant human IL-20. RESULTS: We demonstrate that blocking IL-20 signalling with anti-IL-20 antibodies induces psoriasis resolution and inhibits psoriasis induction. We also demonstrate that continuous IL-20 infusion, together with injection of additional nonactivated leucocytes, promotes induction of psoriasis in nonlesional skin from patients with psoriasis. CONCLUSIONS: The results suggest that IL-20 plays a critical role in the induction and maintenance of psoriasis, and IL-20 is suggested as a new possible specific target in psoriasis treatment.

Electron-induced inversion of helical chirality in copper complexes of N,N-dialkylmethionines.

Stereodynamic complexes of copper were found to undergo inversion of a helical chiral element upon oxidation or reduction. The amino acid methionine was derivatized by the attachment of two chromophores to the nitrogen atom. The resultant ligands formed stable complexes with Cu(I) and Cu(II) salts. For a derivative of a given absolute chirality, the complexes afford nearly mirror image circular dichroism spectra. The spectral changes originate from reorientation of the nitrogen-attached chromophores due to a conformation interconversion driven by the exchange of a carboxylate for a sulfide ligand. The electrically induced chirality inversion coupled with strong interactions with polarized light is unique and may lead to novel chiral molecular devices.

Engaging recreational fishers in management and conservation: global case studies.

Globally, the number of recreational fishers is sizeable and increasing in many countries. Associated with this trend is the potential for negative impacts on fish stocks through exploitation or management measures such as stocking and introduction of non-native fishes. Nevertheless, recreational fishers can be instrumental in successful fisheries conservation through active involvement in, or initiation of, conservation projects to reduce both direct and external stressors contributing to fishery declines. Understanding fishers' concerns for sustained access to the resource and developing methods for their meaningful participation can have positive impacts on conservation efforts. We examined a suite of case studies that demonstrate successful involvement of recreational fishers in conservation and management activities that span developed and developing countries, temperate and tropical regions, marine and freshwater systems, and open- and closed-access fisheries. To illustrate potential benefits and challenges of involving recreational fishers in fisheries management and conservation, we examined the socioeconomic and ecological contexts of each case study. We devised a conceptual framework for the engagement of recreational fishers that targets particular types of involvement (enforcement, advocacy, conservation, management design [type and location], research, and monitoring) on the basis of degree of stakeholder stewardship, scale of the fishery, and source of impacts (internal or external). These activities can be enhanced by incorporating local knowledge and traditions, taking advantage of leadership and regional networks, and creating collaborations among various stakeholder groups, scientists, and agencies to maximize the probability of recreational fisher involvement and project success.

Why are ionic liquid ions mainly associated in water? A Car-Parrinello study of 1-ethyl-3-methyl-imidazolium chloride water mixture.

In this study we present the results of a first principles molecular dynamics simulation of a single 1-ethyl-3-methyl-imidazolium chloride [C(2)C(1)im][Cl] ion pair dissolved in 60 water molecules. We observe a preference of the in plane chloride coordination with respect to the cation ring plane as compared to the energetic slightly more demanding on top coordination. Evaluation of the different radial distribution functions demonstrates that the structure of the hydration shell around the ion pair differs significantly from bulk water and that no true ion pair dissociation in terms of completely autonomous solvation shells takes place on the timescale of the simulation. In addition, dipole moment distributions of the solvent in distinct solvation shells around different functional parts of the [C(2)C(1)im][Cl] ion pair are calculated from maximally localized Wannier functions. The analysis of these distributions gives evidence for a depolarization of water molecules close to the hydrophobic parts of the cation as well as close to the anion. Examination of the angular distribution of different OH(H(2)O)-X angles in turn shows a linear coordination of chloride accompanied by a tangential orientation of water molecules around the hydrophobic groups, being a typical feature of hydrophobic hydration. Based on these orientational aspects, a structural model for the obvious preference of ion pair association is developed, which justifies the associating behavior of solvated [C(2)C(1)im][Cl] ions in terms of an energetically favorable interface between the solvation shells of the anion and the hydrophobic parts of the cation.

Experimental manipulation of telomere length: does it reveal a corner-stone role for telomerase in the natural variability of individual fitness?

Telomeres, the non-coding ends of linear chromosomes, are thought to be an important mechanism of individual variability in performance. Research suggests that longer telomeres are indicative of better health and increased fitness; however, many of these data are correlational and whether these effects are causal are poorly understood. Experimental tests are emerging in medical and laboratory-based studies, but these types of experiments are rare in natural populations, which precludes conclusions at an evolutionary level. At the crossroads between telomere length and fitness is telomerase, an enzyme that can lengthen telomeres. Experimental modulation of telomerase activity is a powerful tool to manipulate telomere length, and to look at the covariation of telomerase, telomeres and individual life-history traits. Here, we review studies that manipulate telomerase activity in laboratory conditions and emphasize the associated physiological and fitness consequences. We then discuss how telomerase's impact on ageing may go beyond telomere maintenance. Based on this overview, we then propose several research avenues for future studies to explore how individual variability in health, reproduction and survival may have coevolved with different patterns of telomerase activity and expression. Such knowledge is of prime importance to fully understand the role that telomere dynamics play in the evolution of animal ageing.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.

Electronic control of helical chirality.

Chiral phenomena are common in living systems. Despite the fact that development of materials has often been inspired by chemistry from the biological world, materials that take advantage of inherent chirality have found relatively few applications. It is therefore probable that much remains to be gained from novel applications of molecular, macromolecular and supramolecular chirality. Among the most intriguing recent advances in studies of chiral materials is the development of mechanisms to control the shape and properties of chiral molecules. Photo-induced helical chirality inversions have been studied for several years and significant achievements have been reported. Recently, electronically triggered systems have drawn significant attention. These technologies offer the potential for development of novel materials that take advantage of photonic or electronic modulation of molecular recognition, optical or mechanical properties.

Reduction of cyclosporine-induced nephrotoxicity by cilastatin following clinical heart transplantation.

The objective of this prospective, randomized, placebo-controlled, single-blinded study in 28 heart-transplanted patients was to investigate whether the dehydropeptidase inhibitor cilastatin reduces cyclosporine-induced nephrotoxicity. Cilastatin is available only in combination with imipenem, a beta-lactam antibiotic to which it is added for reduction of nephrotoxic side-effects of the antimicrobial agent. Patients received either 100 ml placebo (n = 12) or 100 ml (500 mg) imipenem/cilastatin (n = 16) twice perioperatively, and 4 times daily for the first 7 postoperative days. Serum creatinine and urea, as well as urine concentrations of N-acetyl-beta-D-glucosaminidase, which is directly correlated with tubular cell damage, were used as markers for renal function. Thromboxane B2 and 6-keto-prostaglandin F1-alpha serum concentrations were determined to investigate whether there is an imbalance in synthesis of thromboxane A2 and prostacyclin as a possible mechanism for cyclosporine-induced nephrotoxicity. Two placebo patients and 6 patients receiving imipenem/cilastatin had to be excluded from further analysis. Three of 10 placebo patients required hemofiltration, and 2 of them even required hemodialysis, as compared with none in the imipenem/cilastatin group. Creatinine concentrations increased significantly from the second to the fourth postoperative day in the placebo group, but remained nearly normal in cilastatin patients (P < 0.05 for intergroup comparison on postoperative days 2-4). The same trend was observed in urea and N-acetyl-beta-D-glucosaminidase concentrations, without the difference reaching statistical significance. For thromboxane B2 and 6-keto-prostaglandin F1-alpha no differences between the groups could be found. These results suggest that imipenem/cilastatin can counteract acute cyclosporine-induced nephrotoxicity, which appears to be associated with alterations of tubular cell function. The combined use of cyclosporine and imipenem/cilastatin appears to be advantageous in patients following heart transplantation during the initial postoperative period.

Absolute configurations of N,N-dialkyl alpha-amino acids and beta-amino alcohols from exciton-coupled circular dichroism spectra of Cu(II) complexes.

[formula: see text] A circular dichroism technique has been applied to the absolute configurational assignment of acyclic alpha-amino acids and beta-amino alcohols with single stereogenic centers via a one-step derivitization procedure requiring microgram quantities of material. Metal ions fix the geometrical relationship of two chromophores, affording CD spectra that agree with theory on the basis of the expected conformation of the ligands in the metal complexes.

Damage to the cochlea following interrupted exposure to low frequency noise.

This study determines how the magnitude and pattern of cochlear damage is altered when exposure to noise is interrupted by regularly spaced rest periods. Groups of chinchillas were exposed for six hours per session to an octave band of noise with a center frequency of 0.5 kHz. The rest interval between successive exposures varied from 18 to 162 hours. The total energy in these exposures was equal to that in a nine-day continuous exposure at 95 dB sound pressure level. The ears of all animals were prepared for histological study so that the extent of cochlear damage could be determined. The pattern of damage produced by interrupted exposure to low frequency noise was the same as that found with continuous exposure, while the magnitude of damage was usually reduced. The amount of protection provided by a particular rest period was found to be different for the low and high frequency regions of the cochlea. The significance of these findings with regard to the mechanisms of noise damage is discussed.

Effects of lung hyperinflation on mean arterial pressure and postsuctioning hypoxemia.

Our purpose was to determine the effect of five different lung hyperinflation volumes (tidal volume, 12 cc/kg, 14 cc/kg, 16 cc/kg, and 18 cc/kg lean body weight) on mean arterial pressure and postsuctioning hypoxemia (arterial blood gases). Subjects received three consecutive lung hyperinflations at one of the five randomly ordered volumes in 15 seconds via a ventilator "sigh" control at a fraction of inspired oxygen of 1.0. The three lung hyperinflations were followed by 10 seconds of continuous suction (flow rate 16 L/min). The procedure was repeated three times. The sample consisted of eight men and women 4 hours after coronary artery bypass graft surgery. Data indicated a statistically significant (by analysis of variance, p = 0.000) mean increase of 15 mm Hg in mean arterial pressure over the three lung hyperinflation sequences that was not volume dependent. There was a significant increase (p = 0.0001) in arterial oxygen pressure at 0 seconds after suctioning that increased with each increasing lung hyperinflation volume.

What keeps ionic liquids in flow?

The elimination of a hydrogen bond in imidazolium based ionic liquids which results in an increased melting point is investigated by means of static quantum chemical and molecular dynamics simulations.

The expression pattern of interferon-inducible proteins reflects the characteristic histological distribution of infiltrating immune cells in different cutaneous lupus erythematosus subsets.

BACKGROUND: Plasmacytoid dendritic cells and type I interferons (IFNs) are supposed to play a central proinflammatory role in the pathogenesis of cutaneous lupus erythematosus (LE). The IFN-inducible chemokines CXCL9 and CXCL10 are involved in recruiting CXCR3+ effector lymphocytes from the peripheral blood into skin lesions of LE. We hypothesized that the expression pattern of IFN-inducible proteins reflects the characteristic distribution of the inflammatory infiltrate in different subsets of cutaneous LE. OBJECTIVES: To test this hypothesis in patients with LE. METHODS: Lesional skin biopsies taken from patients with different subsets of LE [chronic discoid LE (CDLE), n = 12; subacute cutaneous LE (SCLE), n = 5; LE tumidus (LET), n = 4; LE profundus (LEP), n = 6] were investigated by immunohistochemistry using monoclonal antibodies to the lymphocyte surface markers CD3, CD4, CD8, CD20 and CD68, the cytotoxic proteins Tia1 and granzyme B, the chemokine receptor CXCR3, the specifically type I IFN-inducible protein myxovirus protein A (MxA) and the chemokines CXCL9 and CXCL10. RESULTS: The expression pattern of MxA followed the distribution of the inflammatory infiltrate typically seen in the investigated cutaneous LE subsets. In CDLE and SCLE, expression was focused in the epidermis and upper dermis, while in LET a perivascular and in LEP a subcutaneous pattern was found. Similar findings were obtained for CXCL9 and CXCL10. CONCLUSIONS: Our results demonstrate a close morphological association between the expression pattern of IFN-inducible proteins and the distribution of CXCR3+ CD3+ lymphocytes in all investigated subsets of cutaneous LE. This supports the importance of an IFN-driven inflammation in this condition. Infiltrating lymphocytes carrying CXCL10 in their granules might amplify the lesional inflammation and be responsible for the chronic course of this disease.