Evaluation of interspecific DNA variability in poplars using AFLP and SSR markers

The objective of this paper was to examine interspecific DNA variation in poplars using AFLP and SSR markers. The AFLP and SSR markers polymorphism and its power of discrimination were determinedwithin 13 genotypes of different genetic background (clones, cultivars, hybrids) of two sections (Aigeiros and Tacamahaca) of genus Populus. Twelve sets of PTR and four sets of WPMS microsatellite primers as well as 6 AFLP primer combinations were used in this study. SSR and AFLP markers revealed high power of discrimination, 0.81 and 0.92 respectively. Results obtained using SSR data showed a clear separation of three major clusters, while four major clusters were obtained using AFLP data. Both markers crearly separated two distinct clusters, one included Populus nigra and the other Populus deltoides genotypes. According to both markers, different genetic background were revealed between two clones of Populus trichocarpa. When evaluating polymorphisms within genotypes ofinterest, microsatellite and AFLP DNA markers proved to be a useful tool for distinguishing genetic background of tree clones, cultivars and hybrid genotypes thus grouping them according to their genetic dissimilarity. The results presented in this study could be of significant interest in poplarbreeding programs and could also be used as a valuable annex in new bred clones registration process

Modeling Genomes to Phenomes to Populations in a Changing Climate: The Need for Collaborative Networks

Condensed Abstract Climate is changing globally and its impacts can arise at different levels of biological organization; yet, cross-level consequences of climate change are still poorly understood. Designing effective environmental management and adaptation plans requires implementation of mechanistic models that span the biological hierarchy. Because biological systems are inherently complex and dynamic in nature, dealing with complexities efficiently necessitates simplification of systems or approximation of relevant processes, but there is little consensus on mathematical approaches to scale from genes to populations. Here we present an effort that aims to bring together groups that often do not interact, but that are essential to illuminating the complexities of life: empirical scientists and mathematical modelers, spanning levels of biological organization from genomes to organisms to populations. Through interplay between theory, models, and data, we aim to facilitate the generation of a new synthesis and a conceptual framework for biology across levels

How fast is fast? Eco-evolutionary dynamics and rates of change in populations and phenotypes

It is increasingly recognized that evolution may occur in ecological time. It is not clear, however, how fast evolution – or phenotypic change more generally – may be in comparison with the associated ecology, or whether systems with fast ecological dynamics generally have relatively fast rates of phenotypic change. We developed a new dataset on standardized rates of change in population size and phenotypic traits for a wide range of species and taxonomic groups. We show that rates of change in phenotypes are generally no more than 2/3, and on average about 1/4, the concurrent rates of change in population size. There was no relationship between rates of population change and rates of phenotypic change across systems. We also found that the variance of both phenotypic and ecological rates increased with the mean across studies following a power law with an exponent of two, while temporal variation in phenotypic rates was lower than in ecological rates. Our results are consistent with the view that ecology and evolution may occur at similar time scales, but clarify that only rarely do populations change as fast in traits as they do in abundance

How fast is fast? Eco-evolutionary dynamics and rates of change in populations and phenotypes

It is increasingly recognized that evolution may occur in ecological time. It is not clear, however, how fast evolution – or phenotypic change more generally – may be in comparison with the associated ecology, or whether systems with fast ecological dynamics generally have relatively fast rates of phenotypic change. We developed a new dataset on standardized rates of change in population size and phenotypic traits for a wide range of species and taxonomic groups. We show that rates of change in phenotypes are generally no more than 2/3, and on average about 1/4, the concurrent rates of change in population size. There was no relationship between rates of population change and rates of phenotypic change across systems. We also found that the variance of both phenotypic and ecological rates increased with the mean across studies following a power law with an exponent of two, while temporal variation in phenotypic rates was lower than in ecological rates. Our results are consistent with the view that ecology and evolution may occur at similar time scales, but clarify that only rarely do populations change as fast in traits as they do in abundance

Relativistic two-body system in (1+1)-dimensions

The relativistic two-body system in (1+1)-dimensional quantum electrodynamics is studied. It is proved that the eigenvalue problem for the two-body Hamiltonian without the self-interaction terms reduces to the problem of solving an one-dimensional stationary Schr\"odinger type equation with an energy-dependent effective potential which includes the delta-functional and inverted oscillator parts. The conditions determining the metastable energy spectrum are derived, and the energies and widths of the metastable levels are estimated in the limit of large particle masses. The effects of the self-interaction are discussed.Comment: LATEX file, 21 pp., 4 figure

TCPTP-deficiency in muscle does not alter insulin signalling and glucose homeostasis.

Aims/Hypothesis: Insulin activates the insulin receptor (IR) protein tyrosine kinase and downstream phosphatidylinositol-3-kinase (PI3K)/Akt signalling in muscle to promote glucose uptake. The IR can serve as a substrate for the protein tyrosine phosphatases (PTP) 1B and TCPTP, which share a striking 74% sequence identity in their catalytic domains. PTP1B is a validated therapeutic target for the alleviation of insulin resistance in type 2 diabetes. PTP1B dephosphorylates the IR in liver and muscle to regulate glucose homeostasis, whereas TCPTP regulates IR signalling and gluconeogenesis in the liver. In this study we have assessed for the first time the role of TCPTP in the regulation of IR signalling in muscle. Methods: We generated muscle-specific TCPTP-deficient (MCK-Cre;Ptpn2lox/lox) mice and assessed the impact on glucose homeostasis and muscle IR signalling in chow versus high fat fed mice. Results: Blood glucose and insulin levels, insulin and glucose tolerances and insulininduced muscle IR activation and downstream PI3K/Akt signalling remained unaltered in chow fe

Facile heterocyclic synthesis and antimicrobial activity of polysubstituted and condensed pyrazolopyranopyrimidine and pyrazolopyranotriazine derivatives

Reaction of 6-amino-3-methyl-4-(substituted phenyl)-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (1) with triethylorthoformate followed by treatment with hydrazine hydrate, formic acid, acetic acid, phenylisocyanate, ammonium thiocyanate and formamide afforded the corresponding pyranopyrimidine derivatives 2–6. Cyclocondensation of 1 with cyclohexanone afforded pyrazolopyranoquinoline 7. One-pot process of diazotation and de-diazochlorination of 1 afforded pyrazolopyranotriazine derivative 8, which upon treatment with secondary amines afforded 9 and 10a-c. Condensation of 2 with aromatic aldehyde gave the corresponding Schiff bases 11a,b, the oxidative cyclization of the hydrazone with appropriate oxidant afforded 11-(4-fluorophenyl))-2-(4-substitutedphenyl)-10-methyl-8,11-dihydropyrazolo-[4\u27,3\u27:5,6]pyrano[3,2-e][1,2,4]triazolo[1,5-c]pyrimidines (12a,b). Structures of the synthesized compounds were confirmed by spectral data and elemental analysis. All synthesized compounds were evaluated for antibacterial and antifungal activities compared to norfloxacin and fluconazole as standard drugs. Compounds 9, 10c, 12a and 15 were found to be the most potent antibacterial agents, with activity equal to that of norfloxacin. On the other hand, compound 5 exhibited higher antifungal activity compared to fluconazole

The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs

AMP-activated protein kinase (AMPK) is a metabolic stress-sensing enzyme responsible for maintaining cellular energy homeostasis. Activation of AMPK by salicylate and the thienopyridone A-769662 is critically dependent on phosphorylation of Ser108 in the β1 regulatory subunit. Here, we show a possible role for Ser108 phosphorylation in cell cycle regulation and promotion of pro-survival pathways in response to energy stress. We identify the autophagy initiator Unc-51-like kinase 1 (ULK1) as a β1-Ser108 kinase in cells. Cellular β1-Ser108 phosphorylation by ULK1 was dependent on AMPK β-subunit myristoylation, metabolic stress associated with elevated AMP/ATP ratio, and the intrinsic energy sensing capacity of AMPK; features consistent with an AMP-induced myristoyl switch mechanism. We further demonstrate cellular AMPK signaling independent of activation loop Thr172 phosphorylation, providing potential insight into physiological roles for Ser108 phosphorylation. These findings uncover new mechanisms by which AMPK could potentially maintain cellular energy homeostasis independently of Thr172 phosphorylation

Adipocyte-specific protein tyrosine phosphatase 1B deletion increases lipogenesis, adipocyte cell size and is a minor regulator of glucose homeostasis

Peer reviewedPublisher PD

Antitumor activity from antigen-specific CD8 T cells generated in vivo from genetically engineered human hematopoietic stem cells

The goal of cancer immunotherapy is the generation of an effective, stable, and self-renewing antitumor T-cell population. One such approach involves the use of high-affinity cancer-specific T-cell receptors in gene-therapy protocols. Here, we present the generation of functional tumor-specific human T cells in vivo from genetically modified human hematopoietic stem cells (hHSC) using a human/mouse chimera model. Transduced hHSC expressing an HLA-A*0201–restricted melanoma-specific T-cell receptor were introduced into humanized mice, resulting in the generation of a sizeable melanoma-specific naïve CD8^+ T-cell population. Following tumor challenge, these transgenic CD8^+ T cells, in the absence of additional manipulation, limited and cleared human melanoma tumors in vivo. Furthermore, the genetically enhanced T cells underwent proper thymic selection, because we did not observe any responses against non–HLA-matched tumors, and no killing of any kind occurred in the absence of a human thymus. Finally, the transduced hHSC established long-term bone marrow engraftment. These studies present a potential therapeutic approach and an important tool to understand better and to optimize the human immune response to melanoma and, potentially, to other types of cancer