Criteria for the emergence and evolution of life in the solar system

During the past years we have explored most of the bodies of the solar system by means of the Apollo, Venera, Viking, Voyager, and other space missions. We are now in a better position to be able to compare the conditions of other planets and satellites with those of the Earth in order to determine what is unique about our planet which permitted the emergence and evolution of life on it. On the basis of this and other available scientific information we have arrived at the conclusion that there are at least some twentyfive specific conditions or requirements which have to be fulfilled in order for life as we know it to appear and evolve in a planetary system such as ours. Most of these necessary conditions or requirements are mutually interdependent, but in order to discuss their role in depth they have been divided into five major general areas which are discussed in some detail herein. Planetary criteria, which relate to the physical properties of the planet as it is formed and as it becomes a differentiated cosmic body and potential abode of life. The mass, orbital characteristics and energetic relationships with the central star as well as the discrete separation of gas, liquid and solid phases of the planet are of utmost importance. Chemical criteria, which are concerned with the composition, availability of effective energy sources, and chemical constrainst (solvent, pH range, redox potential) of the environment(s) where reactions take place for the prebiological formation of biochemical compounds. Protobiological criteria, which relate to the prebiologically synthesized oligomeric and polymeric biomolecules, how they interact cooperatively to form protobiological structures and functions (replication, catalysis, information transfer, etc.) and self-assemble to give rise to a living system. Evolutionary criteria, which are concerned with the processes responsible for the increase in complexity of organisms by genomic multiplication, symbiotic integration and cellular differentiation, as well as with the negentropic ability of organisms to continuously recycle all the volatile biogenic elements. Altogether these processes made possible the development and evolution of life from the simplest prokaryotic cell ancestor to a cognitive and manipulative multicellular organism (man).In order to extend this inquiry to other systems beyond our solar system a fifth set of requirements based on astronomical observations is also discussed, namely, theStellar criteria, which relate to the elemental composition mass, lifetime, and other features of Main Sequence stars which may be surrounded by planetary systems similar to our own. Finally, a brief review is made on the probability of the existence of extraterrestrial life as well as of civilizations capable of interstellar communication in our Galaxy.Paper presented at the 6th College Park Colloquium, October 1981.     

Haptoglobin genotype predicts development of coronary artery calcification in a prospective cohort of patients with type 1 diabetes

Background

Soluble ST2, a member of the of the Toll/IL-1 superfamily, is a novel biomarker with exceptional predictive value in heart failure and myocardial infarction- related mortality as well as in acute dyspneic states. Soluble ST2 is considered a decoy receptor of IL 33 that blocks the protective effects of the cytokine in atherosclerosis and cardiac remodeling. In the present study we investigated the differences in the levels of soluble ST2, BNP and hs-CRP between healthy controls and patients with type 2 diabetes with and without left ventricular diastolic dysfunction. A secondary aim was to investigate correlations between sST2 and other biomarkers of type 2 diabetes, such as HbA1c.

Methods

158 volunteers were recruited and underwent a complete Doppler-echocardiographic evaluation of both systolic & diastolic cardiac function. All subjects with ejection fraction < 50% were excluded. The study population was divided in 4 groups as follows: A: 42 healthy controls, B: 18 subjects without diabetes with LVDD, C: 48 patients with type 2 diabetes without LVDD & D: 50 patients with type 2 diabetes & LVDD. ELISA technique was performed to measure sST2 levels. Statistical analysis was performed with Kruskal-Wallis & Mann-Whitney test (continuous variables), chi squared & Fischer exact test (discrete variables), Spearman coefficient (univariate analysis) and step-wise backward method (multivariate analysis).

Results

Patients with type 2 diabetes with (p < 0.001) or without LVDD (p = 0.007) had higher serum ST2 levels compared to healthy controls, state found also for hs-CRP levels but not for the corresponding BNP levels (p = 0.213 & p = 0.207 respectively). Patients with type 2 diabetes & LVDD had higher serum ST2 in relation to diabetic patients without LVDD (p = 0.001). In multivariate analysis HbA1c positively and independently correlated with sST2 levels in both groups of patients with type 2 diabetes.

Conclusions

Patients with type 2 diabetes exhibit higher sST2 levels compared to healthy controls. The presence of LVDD in patients with type 2 diabetes is associated with even higher sST2 levels. A significant correlation between glycemic control and sST2 levels was also revealed.     

Soluble interleukin-2 receptor as a marker for progression of coronary artery calcification in type 1 diabetes

INTRODUCTION: Soluble interleukin-2 receptor (sIL2r), a marker of T cell activation, is elevated in inflammatory processes, such as rheumatoid arthritis, hepatitis and neoplasm. We explored a potential association between plasma sIL2r levels and progression of coronary artery calcification (CAC), a marker for subclinical atherosclerosis, in a prospectively followed cohort of type 1 diabetic and non-diabetic subjects, aged 20-59 years, with no history of coronary artery disease. MATERIALS AND METHODS: CAC progression was assessed by electron beam tomography over 2.6 years (range 1.6-3.2). Plasma sIL2r levels were measured in a nested case-control substudy of 98 subjects (67 diabetic, 31 non-diabetic) with and 173 subjects (84 diabetic, 89 non-diabetic) without significant CAC progression. Log-transformed sIL2r levels were analyzed by conditional logistic regression to compare subjects with and without significant CAC progression. RESULTS: SIL2r was a significant predictor for CAC progression after adjusting for presence of baseline CAC, age, gender, diabetes status, baseline calcium volume score and adiponectin (OR 1.99, 95% CI 1.09-3.61, p = 0.02 for a doubling of sIL2r level). Addition of BMI, LDL, HDL, hypertension, smoking status, HbA1c, CRP, fibrinogen, homocysteine and PAI-1 to regression models weakened but did not remove sIL2r as a predictor of CAC progression. There was no indication that this effect was different by diabetes status (p = 0.6 for diabetes-sIL2r interaction). DISCUSSION: Elevated plasma sIL2r is associated with CAC progression independent of traditional coronary artery disease risk factors in type 1 diabetic and non-diabetic young adults. SIL2r should be considered as a novel marker of inflammation leading to coronary artery disease.     

Endoreduplication in cucumber (Cucumis sativus) seeds during development, after processing and storage, and during germination

Flow cytometry was used to study endoreduplication in developing, stored and germinating seeds of cucumber ( Cucumis sativus ). Fruits growing in a commercial seed production field were collected every 7 days, starting 14 days after pollination (DAP) up to 63 DAP (commercial harvest time). Seeds were isolated and the proportion of nuclei with different DNA contents in the whole seeds and in the embryos was analysed. Germination capacity of fresh and dried seeds at 25°C was established. In addition, the same analyses were performed on the seeds after processing (fermentation, drying and cleaning), following 1 and 2 years of storage, and after imbibition for 3, 6 and 12 h. In the young developing seeds, endoreduplication up to 128C occurred but this decreased to 8C by maturity. The proportion of endosperm nuclei was the highest at 21 DAP (30%) and then decreased to below 14% at harvest and 8% after processing. In the mature processed seeds, the majority of embryo nuclei (about 80%) contained 2C DNA; however, about 2% of endoreduplicated (8C) nuclei were still present. Seeds did not show any germination capacity up to 21 DAP; then it gradually increased to reach 100% as early as 49 DAP, 2 weeks before commercial harvest time. The relationship between seed maturity, germination and cell cycle status is discussed. The mean C-value of the seed cells as well as the (4C + 8C + 16C)/2C ratio are recommended as markers of cucumber seed maturity and the advancement of germination/priming (the stage of germination sensu stricto ).     

Urinary F2-isoprostanes in young healthy children at risk for type 1 diabetes mellitus

Oxidative stress has been linked to many diseases, but little information exists on biomarkers of oxidative stress in healthy children. The purpose of this study was to describe factors that correlate with urinary F2-isoprostanes, an indicator of oxidative stress, and to establish normal concentrations of F2-isoprostanes in children at risk to develop type 1 diabetes mellitus. Creatinine-adjusted urinary F2-isoprostanes were assessed in 342 Denver children under the age of 7 years, from whom we had collected data during 769 clinic visits from August 1997 through January 2001 (mean 2.3 visits per child). Children were identified by newborn screening for HLA-markers, of varying degrees of prediction, for the development of type 1 diabetes. Plasma antioxidants and carotenoids, age at clinic visit, vitamin supplement use, exposure to environmental tobacco smoke, gender, and race were evaluated as correlates to the degree of oxidative stress, using mixed models for longitudinal data. F2-isoprostane levels were highest in infancy and decreased nonlinearly until 7 years. Female gender, HLA-DR3/4 genotype, higher plasma gamma-tocopherol:total lipids ratio, and lower alpha-carotene:total lipids ratio correlated with higher F2-isoprostane levels. Normal values in this healthy population can be used as the basis for future studies of disease mechanisms involving oxidative stress.     

The Effect of Nutritional Factors and Plant Growth Regulators on Micropropagation and Production of Phenolic Acids and Saponins from Plantlets and Adventitious Root Cultures of Eryngium maritimum L.

Eryngium maritimum L. is a valuable medicinal species, but since it is protected plant, collection from natural populations is forbidden. Therefore, establishing an efficient system for micropropagation of this species is desirable. To determine the optimal nutritional factors needed for shoot multiplication, root development and secondary metabolites accumulation, different media and plant growth regulators were tested. The highest plant regeneration efficiency (over 96 %), with 4.4 shoots per explant was induced on Murashige and Skoog (MS) medium supplemented with 1.0 mg L^?1 benzyladenine (BA) and 0.1 mg L^?1 indole-3-acetic acid (IAA). The in vitro-regenerated shoots were rooted (83.3–100 %) and transferred to an experimental plot with 62 % efficiency. Flow cytometric analysis revealed no variation in nuclear DNA content in field- and in vitro-delivered plant material. Ultra high performance liquid chromatography (UHPLC) indicated that multiple shoots and roots from in vitro-regenerated plantlets and adventitious root cultures maintained the production of rosmarinic (RA) and chlorogenic (CGA) acids and triterpenoid saponins found in the rosette leaves and roots of E. maritimum intact plants. UHPLC revealed a 12-fold increase of RA and CGA and 3.2-fold higher accumulation of triterpenoid saponins in roots of in vitro-derived plantlets in comparison to roots from field-grown plants. Adventitious root cultures allowed continuous growth of excised root in liquid media with or without exogenous auxins. The roots grown in liquid medium supplemented with 0.1 mg L^?1 IAA showed higher (227-fold) phenolic acids accumulation than those without auxin. Obtained results confirmed that micropropagation is a useful strategy in the protection of endangered species and a renewable source of a high quality plant material for secondary metabolites production.     

Extrapancreatic Autoantibody Profiles in Type I Diabetes

Type I diabetes (T1D) is an autoimmune disease characterized by destruction of insulin-producing β-cells in the pancreas. Although several islet cell autoantigens are known, the breadth and spectrum of autoantibody targets has not been fully explored. Here the luciferase immunoprecipitation systems (LIPS) antibody profiling technology was used to study islet and other organ-specific autoantibody responses in parallel. Examination of an initial cohort of 93 controls and 50 T1D subjects revealed that 16% of the diabetic subjects showed anti-gastric ATPase autoantibodies which did not correlate with autoantibodies against GAD65, IA2, or IA2-β. A more detailed study of a second cohort with 18 potential autoantibody targets revealed marked heterogeneity in autoantibody responses against islet cell autoantigens including two polymorphic variants of ZnT8. A subset of T1D subjects exhibited autoantibodies against several organ-specific targets including gastric ATPase (11%), thyroid peroxidase (14%), and anti-IgA autoantibodies against tissue transglutaminase (12%). Although a few T1D subjects showed autoantibodies against a lung-associated protein KCNRG (6%) and S100-β (8%), no statistically significant autoantibodies were detected against several cytokines. Analysis of the overall autoantibody profiles using a heatmap revealed two major subgroups of approximately similar numbers, consisting of T1D subjects with and without organ-specific autoantibodies. Within the organ-specific subgroup, there was minimal overlap among anti-gastric ATPase, anti-thyroid peroxidase, and anti-transglutaminase seropositivity, and these autoantibodies did not correlate with islet cell autoantibodies. Examination of a third cohort, comprising prospectively collected longitudinal samples from high-risk individuals, revealed that anti-gastric ATPase autoantibodies were present in several individuals prior to detection of islet autoantibodies and before clinical onset of T1D. Taken together, these results suggest that autoantibody portraits derived from islet and organ-specific targets will likely be useful for enhancing the clinical management of T1D.     

Identification of Non-HLA Genes Associated with Celiac Disease and Country-Specific Differences in a Large,International Pediatric Cohort

Objectives

There are significant geographical differences in the prevalence and incidence of celiac disease that cannot be explained by HLA alone. More than 40 loci outside of the HLA region have been associated with celiac disease. We investigated the roles of these non-HLA genes in the development of tissue transglutaminase autoantibodies (tTGA) and celiac disease in a large international prospective cohort study.

Methods

A total of 424,788 newborns from the US and European general populations and first-degree relatives with type 1 diabetes were screened for specific HLA genotypes. Of these, 21,589 carried 1 of the 9 HLA genotypes associated with increased risk for type 1 diabetes and celiac disease; we followed 8676 of the children in a 15 y prospective follow-up study. Genotype analyses were performed on 6010 children using the Illumina ImmunoChip. Levels of tTGA were measured in serum samples using radio-ligand binding assays; diagnoses of celiac disease were made based on persistent detection of tTGA and biopsy analysis. Data were analyzed using Cox proportional hazards analyses.

Results

We found 54 single-nucleotide polymorphisms (SNPs) in 5 genes associated with celiac disease (TAGAP, IL18R1, RGS21, PLEK, and CCR9) in time to celiac disease analyses (10⁻⁴>P>5.8x10⁻⁶). The hazard ratios (HR) for the SNPs with the smallest P values in each region were 1.59, 1.45, 2.23, 2.64, and 1.40, respectively. Outside of regions previously associated with celiac disease, we identified 10 SNPs in 8 regions that could also be associated with the disease (P<10⁻⁴). A SNP near PKIA (rs117128341, P = 6.5x10⁻⁸, HR = 2.8) and a SNP near PFKFB3 (rs117139146, P<2.8x10⁻⁷, HR = 4.9) reached the genome-wide association threshold in subjects from Sweden. Analyses of time to detection of tTGA identified 29 SNPs in 2 regions previously associated with celiac disease (CTLA4, P = 1.3x10⁻⁶, HR = 0.76 and LPP, P = 2.8x10⁻⁵, HR = .80) and 6 SNPs in 5 regions not previously associated with celiac disease (P<10⁻⁴); non-HLA genes are therefore involved in development of tTGA.

Conclusions

In conclusion, using a genetic analysis of a large international cohort of children, we associated celiac disease development with 5 non-HLA regions previously associated with the disease and 8 regions not previously associated with celiac disease. We identified 5 regions associated with development of tTGA. Two loci associated with celiac disease progression reached a genome-wide association threshold in subjects from Sweden.     

The Association between IgG4 Antibodies to Dietary Factors,Islet Autoimmunity and Type 1 Diabetes: The Diabetes Autoimmunity Study in the Young

Background

Infant dietary exposures have been linked to type 1 diabetes (T1D) development. IgG4 antibody responses to food antigens are associated with food intolerances but have not been explored prospectively in the period preceding T1D.

Methods

Using a case-cohort design, IgG4 antibodies to ß-lactoglobulin, gluten, and ovalbumin were measured in plasma collected annually from 260 DAISY participants. Of those, 77 developed islet autoimmunity (IA), defined as positive for either insulin, GAD65 or IA-2 autoantibodies on two consecutive visits, and 22 developed T1D.

Results

In mixed model analysis adjusting for HLA-DR status, T1D family history, age and ethnicity, higher ß-lactoglobulin IgG4 concentrations were associated with shorter breastfeeding duration (beta = −0.03, 95% Confidence Interval: −0.05, −0.006) and earlier first cow’s milk exposure (beta = −0.04, 95% Confidence Interval: −0.08, 0.00). Higher gluten IgG4 was associated with older age at gluten introduction (beta = 0.06, 95% Confidence Interval: 0.00, 0.13). In proportional hazards analysis adjusting for HLA-DR status, T1D family history and ethnicity, IgG4 against individual or multiple dietary antigens throughout childhood were not associated with IA. In addition, mean antigen-specific IgG4 concentrations in infancy (age <2 years) were not associated with risk of IA nor progression to T1D. Higher ovalbumin IgG4 at first IA positive visit was marginally associated with progression to T1D (Hazard Ratio: 1.39, 95% Confidence Interval: 1.00, 1.92).

Conclusion

We found no association between the IgG4 response to β-lactoglobulin, gluten, and the development of either IA or T1D. The association between higher ovalbumin and progression to T1D in children with IA should be explored in other populations.