Do telomeres influence pace-of-life-strategies in response to environmental conditions over a lifetime and between generations?

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordEuropean Union Horizon 2020Estonian Research Counci

Oxygenated conditions in the aftermath of the Lomagundi-Jatuli Event : the carbon isotope and rare earth element signatures of the Paleoproterozoic Zaonega Formation, Russia

This study was supported by Estonian Research Council project PRG447, and the Estonian Centre of Analytical Chemistry. K.P. and A.L. were supported by the Research Council of Norway through its Centres of Excellence funding scheme grant No. 223259. K.P. acknowledges the Estonian Research Council grant MOBJD542 and T.M. PUT611.The c. 2.0 Ga Zaonega Formation of the Onega Basin (NW Russia) has been central in efforts to understand what led to the initial rise (Great Oxidation Event, GOE) and postulated fall in free atmospheric oxygen and associated high-amplitude carbon cycle excursions, the Lomagundi-Jatuli Event (LJE) and subsequent Shunga Event during Paleoproterozoic time. The Formation accumulated shortly after the LJE and encompasses both the recovery in the carbon cycle and hypothesised contraction of the oceanic oxidant pool. However, interpreting the correct environmental context recorded by geochemical signatures in the Zaonega rocks is difficult due to a complex depositional and diagenetic history. In order to robustly constrain that history, we undertook a multiproxy study (mineralogy, petrography, carbon isotope and rare earth element composition) of carbonate beds in the upper part of the Zaonega Formation recovered in the 102-m composite section of the OnZap drill-cores. Our findings differentiate primary environmental signatures from secondary overprinting and show that: (i) the best-preserved carbonate beds define an upwards increasing δ13Ccarb trend from c. -5.4‰ to near 0‰; and that (ii) large intra-bed δ13Ccarb variations reflect varying contributions of methanotrophic dissolved inorganic carbon (DIC) to the basinal DIC pool. Rare earth element and yttrium (REYSN) patterns confirm a marine origin of the carbonate beds whereas a consistent positive EuSN anomaly suggests a strong high temperature hydrothermal input during accumulation of the Zaonega Formation. Importantly, the presence of a negative CeSN anomaly in the REYSN pattern indicates an oxygenated atmosphere-ocean system shortly after the LJE and indicates that models invoking a fall in oxygen at that time require reassessment.PostprintPeer reviewe

Complement C3 variant and the risk of age-related macular degeneration

Background: Age-related macular degeneration is the most common cause of blindness in Western populations. Susceptibility is influenced by age and by genetic and environmental factors. Complement activation is implicated in the pathogenesis.Methods: We tested for an association between age-related macular degeneration and 13 single-nucleotide polymorphisms (SNPs) spanning the complement genes C3 and C5 in case subjects and control subjects from the southeastern region of England. All subjects were examined by an ophthalmologist and had independent grading of fundus photographs to confirm their disease status. To test for replication of the most significant findings, we genotyped a set of Scottish cases and controls.Results: The common functional polymorphism rs2230199 (Arg80Gly) in the C3 gene, corresponding to the electrophoretic variants C3S (slow) and C3F (fast), was strongly associated with age-related macular degeneration in both the English group (603 cases and 350 controls, P=5.9 x 10(sup -5)) and the Scottish group (244 cases and 351 controls, P=5.0 x 10(sup -5)). The odds ratio for age-related macular degeneration in C3 S/F heterozygotes as compared with S/S homozygotes was 1.7 (95% confidence interval [CI], 1.3 to 2.1); for F/F homozygotes, the odds ratio was 2.6 (95% CI, 1.6 to 4.1). The estimated population attributable risk for C3F was 22%.Conclusions: Complement C3 is important in the pathogenesis of age-related macular degeneration. This finding further underscores the influence of the complement pathway in the pathogenesis of this disease

Utilizing stimulated Raman scattering microscopy to study intracellular distribution of label-free ponatinib in live cells

Stimulated Raman scattering (SRS) microscopy represents a powerful method for imaging label-free drug dis-tribution with high resolution. SRS was applied to image label-free ponatinib with high sensitivity and speci-ficity in live human chronic myeloid leukemia (CML) cell lines. This was achieved at biologically relevant, na-nomolar concentrations; allowing determination of ponatinib uptake and sequestration into lysosomes during the development of acquired drug resistance and an improved understanding of target engagement

Human Cutaneous Dendritic Cells Migrate Through Dermal Lymphatic Vessels in a Skin Organ Culture Model

The capacity to migrate from peripheral tissues, where antigen is encountered, to lymphoid organs, where the primary immune response is initiated, is crucial to the immunogenic function of dendritic cells (DC). The skin is a suitable tissue to study migration. DC were observed to gather in distinct nonrandom arrays (“cords”) in the dermis upon culture of murine whole skin explants. It is assumed that cords represent lymphatic vessels. Using a similar organ culture model with human split-thickness skin explants, we investigated migration pathways in human skin.We made the following observations. 1) Spontaneous emigration of Langerhans cells took place in skin cultured for 1–3 d. Nonrandom distribution patterns of strongly major histocompatibility complex class II-expressing DC (cords) occurred in cultured dermis. A variable, yet high (>50%) percentage of these DC coexpressed the Birbeck granule-associated antigen “Lag” Ultrastructurally, the cells corresponded to mature DC. 2) Electron microscopy proved that the dermal structures harboring the accumulations of DC (i.e., cords) were typical lymph vessels. Moreover, markers for blood endothelia (monoclonal antibody PAL-E, Factor VIII-related antigen) and markers for cords (strong major histocompatibility complex class II expression on nonrandomly arranged, hairy-appearing cells) were expressed in a mutually exclusive pattern. 3) On epidermal sheets we failed to detect gross changes in the levels of expression of adhesion molecules (CD44, CD54/ICAM-1, E-cadherin) on keratinocytes in the course of the culture period.The reactivity of a part of the DC in the dermal cords with Birbeck granule-specific monoclonal antibody “Lag” suggests that the migratory population is composed of both epidermal Langerhans cells and dermal DC. We conclude that this organ culture model may prove helpful in resolving pathways and mechanisms of DC migration

Probing scalar particle and unparticle couplings in e+ e- -> t tbar with transversely polarized beams

In searching for indications of new physics scalar particle and unparticle couplings in e^+ e^- \to t\bar t, we consider the role of transversely polarized initial beams at e^+ e^- colliders. By using a general relativistic spin density matrix formalism for describing the particles spin states, we find analytical expressions for the squared amplitude of the process with t or \bar t polarization measured, including the anomalous coupling contributions. Thanks to the transversely polarized initial beams these contributions are first order anomalous coupling corrections to the Standard Model (SM) contributions. We present and analyse the main features of the SM and anomalous coupling contributions. We show how differences between SM and anomalous coupling contributions provide means to search for anomalous coupling manifestations at future e^+ e^- linear colliders.Comment: 28 pages in LaTeX, including 7 encapsulated PostScript figures, published versio

Hydrothermal dedolomitisation of carbonate rocks of the Paleoproterozoic Zaonega Formation, NW Russia — Implications for the preservation of primary C isotope signals

This study was supported by Estonian Science Agency project PUT696 and PRG447, and Estonian Centre of Analytical Chemistry. K.P. and A.L. were supported by the Research Council of Norway through its Centres of Excellence funding scheme grant No. 223259.The Paleoproterozoic Zaonega Formation in Karelia, NW Russia, has played a key role in understanding the environmental conditions postdating the Great Oxidation and Lomagundi-Jatuli Events. Its carbonate- and organic-rich rocks (shungite) define the postulated Shunga Event representing an accumulation of very organic-rich sediments at c. 2 Ga and are central in ideas about changing ocean-atmosphere composition in the wake of those worldwide biogeochemical phenomena. Our work focussed on a key interval of carbonate rocks in the upper part of the Formation to: (i) obtain new high-resolution carbon, oxygen and strontium isotope data complemented by detailed petrography and mineralogical characterisation and (ii) expand upon previous studies by using our data to constrain geochemical modelling and show in greater detail how magmatic hydrothermal fluids induced dedolomitisation and altered geochemical signals. Our findings show that the δ13Ccarb of calcite-rich intervals are the most altered, with values between −16.9 to 0.6‰, whereas the dolomite-dominated parts retain the best-preserved (i.e. most original) values. Those define a trend of steadily increasing δ13Ccarb, from −6 to +0.5‰, which we interpret as a return to normal marine conditions and carbonate‑carbon values following the Lomagundi-Jatuli Event.PostprintPeer reviewe

Adsorption of CO on a Platinum (111) surface - a study within a four-component relativistic density functional approach

We report on results of a theoretical study of the adsorption process of a single carbon oxide molecule on a Platinum (111) surface. A four-component relativistic density functional method was applied to account for a proper description of the strong relativistic effects. A limited number of atoms in the framework of a cluster approach is used to describe the surface. Different adsorption sites are investigated. We found that CO is preferably adsorbed at the top position.Comment: 23 Pages with 4 figure

Entry Into Afferent Lymphatics and Maturation In Situ of Migrating Murine Cutaneous Dendritic Cells

An important property of dendritic cells (DC), which contributes crucially to their strong immunogenic function, is their capacity to migrate from sites of antigen capture to the draining lymphoid organs. Here we studied in detail the migratory pathway and the differentiation of DC during migration in a skin organ culture model and, for comparison, in the conventional contact hypersensitivity system. We report several observations on the capacity of cutaneous DC to migrate in mouse ear skin. (i) Upon application of contact allergens in vivo the density of Langerhans cells in epidermal sheets decreased, as determined by immunostaining for major histocompatibility complex class II, ADPase, F4/80, CD11b, CD32, NLDC-145/DEC-205, and the cytoskeleton protein vimentin. Evaluation was performed by computer assisted morphometry. (ii) Chemically related nonsensitizing or tolerizing compounds left the density of Langerhans cells unchanged. (iii) Immunohistochemical double-staining of dermal sheets from skin organ cultures for major histocompatibility complex class II and CD54 excluded blood vessels as a cutaneous pathway of DC migration. (iv) Electron microscopy of organ cultures revealed dermal accumulations of DC (including Birbeck granule containing Langerhans cells) within typical lymphatic vessels. (v) Populations of migrating DC in organ cultures upregulated markers of maturity (the antigen recognized by monoclonal antibody 2A1, CD86), but retained indicators of immaturity (invariant chain, residual antigen processing function). These data provide additional evidence that during both the induction of contact hypersensitivity and in skin organ culture, Langerhans cells physically leave the epidermis. Both Langerhans cells and dermal DC enter lymphatic vessels. DC mature while they migrate through the skin

MRI plaque imaging reveals high-risk carotid plaques especially in diabetic patients irrespective of the degree of stenosis

<p>Abstract</p> <p>Background</p> <p>Plaque imaging based on magnetic resonance imaging (MRI) represents a new modality for risk assessment in atherosclerosis. It allows classification of carotid plaques in high-risk and low-risk lesion types (I-VIII). Type 2 diabetes mellitus (DM 2) represents a known risk factor for atherosclerosis, but its specific influence on plaque vulnerability is not fully understood. This study investigates whether MRI-plaque imaging can reveal differences in carotid plaque features of diabetic patients compared to nondiabetics.</p> <p>Methods</p> <p>191 patients with moderate to high-grade carotid artery stenosis were enrolled after written informed consent was obtained. Each patient underwent MRI-plaque imaging using a 1.5-T scanner with phased-array carotid coils. The carotid plaques were classified as lesion types I-VIII according to the MRI-modified AHA criteria. For 36 patients histology data was available.</p> <p>Results</p> <p>Eleven patients were excluded because of insufficient MR-image quality. DM 2 was diagnosed in 51 patients (28.3%). Concordance between histology and MRI-classification was 91.7% (33/36) and showed a Cohen's kappa value of 0.81 with a 95% CI of 0.98-1.15. MRI-defined high-risk lesion types were overrepresented in diabetic patients (n = 29; 56.8%). Multiple logistic regression analysis revealed association between DM 2 and MRI-defined high-risk lesion types (OR 2.59; 95% CI [1.15-5.81]), independent of the degree of stenosis.</p> <p>Conclusion</p> <p>DM 2 seems to represent a predictor for the development of vulnerable carotid plaques irrespective of the degree of stenosis and other risk factors. MRI-plaque imaging represents a new tool for risk stratification of diabetic patients.</p> <p>See Commentary: <url>http://www.biomedcentral.com/1741-7015/8/78/abstract</url></p