Probing the influence of the Tp ligand on reactions of Pt(II) and Pt(IV)

Transformations of platinum(II) to platinum(IV) using organic reagents have been studied. A tridentate ligand system, hydridotris(3,5-dimethylpyrazolyl)borate - Tp prime was shown to promote reactions at the platinum center. Three types of organic reagents have been investigated: alkynes, carbon monoxide, and isonitriles. Reaction of the Tp prime PtMe fragment with terminal alkynes results in eta2-binding of the alkyne. Oxidative addition of the alkyne occurs upon gentle heating. Kinetic studies indicate that electron donating groups on the alkyne increase the rate of oxidative addition and that approaching the transition state increases the entropy. The proposed mechanism of oxidative addition proceeds through a transition state in which the third arm of the Tp prime ligand is dechelated, a process that would be made easier by an electron donating group on the alkyne. In contrast, the reaction of alkynes (both terminal and internal) with the Tp prime PtPh fragment does not produce eta2-bound alkyne adducts. Instead, phenyl migration to the alkyne followed by ortho C-H bond activation occurs resulting in formation of unsaturated metallacycles. Conversion of Tp prime Pt(Me)(CO) to the acyl complex, Tp prime Pt(C(Me)=O)MeH has been accomplished by nucleophilic attack with MeLi followed by addition of HCl. The Pt(IV) acyl complex reacts with adventitious water in the presence of CO to produce the acyl dihydride product, Tp prime Pt(C(Me)=O)H2, from a proposed metal mediated water gas shift reaction. Upon addition of acid, formation of dihydrogen is observed. An analogous carboxamido complex, Tp prime Pt((C=O)NHR)Me2, has also been synthesized. Deprotonation of the carboxamido ligand followed by acidification produces Tp prime PtMe2H, presumably after elimination of free isocyanate. Reaction of the Tp prime PtMe fragment with 2,6-dimethylphenyl isonitrile produces a four-coordinate sigma-bound isonitrile complex. This complex is susceptible to nucleophilic attack at the carbon of the isonitrile, producing an iminoacyl moiety. Protonation at the nitrogen of the iminoacyl complex results in an aminocarbene complex. The availability of the lone pair at the nitrogen of the free pyrazole arm of the Tp prime ligand provides access to rare six-coordinate iminoacyl and aminocarbene complexes

Comparison between two analytic strategies to detect linkage to obesity with genetically determined age of onset: the Framingham Heart Study

BACKGROUND: Genes have been found to influence the age of onset of several diseases and traits. The occurrence of many chronic diseases, obesity included, appears to be strongly age-dependent. However, an analysis of potential age of onset genes for obesity has yet to be reported. There are at least two analytic methods for determining an age of onset gene. The first is to consider a person affected if they possess the trait before a certain age (an early age of onset phenotype). The second is to define the phenotype based on the residual from a survival analysis. RESULTS: No regions provided evidence for linkage at the more stringent level of p < 0.001. However, five regions showed consistent suggestive evidence for linkage (one marker with p < 0.01 and a second contiguous marker at p < 0.05). These regions were chromosome 1 (280–294 cM) and chromosome 16 (56–64 cM) for overweight using the survival analysis residual method and chromosome 13 (102–122 cM), chromosome 17 (127–138 cM), and chromosome 19 (23–47 cM) for obese before age 35. CONCLUSION: Only one region (chromosome 19 at 23–47 cM) showed somewhat consistent results between the two analytic methods. Potential reasons for inconsistent results between the two methods, as well as their strengths and weaknesses, are discussed. The use of both methods together to explore the genetics of the age of onset of a trait may prove to be beneficial in determining a gene that is linked only to an early age of onset phenotype versus one that determines age of onset through all age groups

Host and viral determinants for MxB restriction of HIV-1 infection

Background: Interferon-induced cellular proteins play important roles in the host response against viral infection. The Mx family of dynamin-like GTPases, which include MxA and MxB, target a wide variety of viruses. Despite considerable evidence demonstrating the breadth of antiviral activity of MxA, human MxB was only recently discovered to specifically inhibit lentiviruses. Here we assess both host and viral determinants that underlie MxB restriction of HIV-1 infection. Results: Heterologous expression of MxB in human osteosarcoma cells potently inhibited HIV-1 infection (~12-fold), yet had little to no effect on divergent retroviruses. The anti-HIV effect manifested as a partial block in the formation of 2-long terminal repeat circle DNA and hence nuclear import, and we accordingly found evidence for an additional post-nuclear entry block. A large number of previously characterized capsid mutations, as well as mutations that abrogated integrase activity, counteracted MxB restriction. MxB expression suppressed integration into gene-enriched regions of chromosomes, similar to affects observed previously when cells were depleted for nuclear transport factors such as transportin 3. MxB activity did not require predicted GTPase active site residues or a series of unstructured loops within the stalk domain that confer functional oligomerization to related dynamin family proteins. In contrast, we observed an N-terminal stretch of residues in MxB to harbor key determinants. Protein localization conferred by a nuclear localization signal (NLS) within the N-terminal 25 residues, which was critical, was fully rescuable by a heterologous NLS. Consistent with this observation, a heterologous nuclear export sequence (NES) abolished full-length MxB activity. We additionally mapped sub-regions within amino acids 26–90 that contribute to MxB activity, finding sequences present within residues 27–50 particularly important. Conclusions: MxB inhibits HIV-1 by interfering with minimally two steps of infection, nuclear entry and post-nuclear trafficking and/or integration, without destabilizing the inherent catalytic activity of viral preintegration complexes. Putative MxB GTPase active site residues and stalk domain Loop 4 -- both previously shown to be necessary for MxA function -- were dispensable for MxB antiviral activity. Instead, we highlight subcellular localization and a yet-determined function(s) present in the unique MxB N-terminal region to be required for HIV-1 restriction. Electronic supplementary material The online version of this article (doi:10.1186/s12977-014-0090-z) contains supplementary material, which is available to authorized users

Molecular motion in cell membranes: analytic study of fence-hindered random walks

A theoretical calculation is presented to describe the confined motion of transmembrane molecules in cell membranes. The study is analytic, based on Master equations for the probability of the molecules moving as random walkers, and leads to explicit usable solutions including expressions for the molecular mean square displacement and effective diffusion constants. One outcome is a detailed understanding of the dependence of the time variation of the mean square displacement on the initial placement of the molecule within the confined region. How to use the calculations is illustrated by extracting (confinement) compartment sizes from experimentally reported published observations from single particle tracking experiments on the diffusion of gold-tagged G-protein coupled mu-opioid receptors in the normal rat kidney cell membrane, and by further comparing the analytical results to observations on the diffusion of phospholipids, also in normal rat kidney cells.Comment: 10 pages, 5 figure

The Role of Demography in the Transition to Sustainable Societies

Currently, although the global population has surpassed 7.5 billion and continues to increase in about 80 million each year, attention to demography is almost absent in most of the studies and publications related to the current situation of planetary emergency and the necessary transition to sustainable societies. For this reason, our first aim in this paper has been to discuss if this current lack of attention to demography is justified or not. With this purpose, we begin considering the scientific meaning of Sustainability, in order to overlay distorted and impoverish views of this concept that may hinder our study. Then, we analyse the reasons given by experts for and against the incidence of demographic growth in the current unsustainable situation of planetary emergency. Finally, we present proposals to face the ensemble of interconnected socio-environmental problems (including demographic evolution), to make possible an appropriate transition to sustainable societies. Aunque la población mundial ha sobrepasado los 7500 millones y continúa aumentando anualmente en alrededor de 80 millones, la atención a la demografía está hoy prácticamente ausente en la mayoría de los estudios y publicaciones acerca de la actual situación de emergencia planetaria y la necesidad de una transición a sociedades sostenibles. Con el propósito de analizar si esta falta de atención a la demografía está o no justificada, en esta contribución comenzamos discutiendo el significado científico de Sostenibilidad socioambiental, para evitar concepciones distorsionadas y empobrecidas de este concepto que pueden dificultar dicho análisis. A continuación estudiaremos las razones dadas por distintos expertos a favor y en contra de la incidencia del crecimiento demográfico en la insostenible situación actual de emergencia planetaria. Finalmente presentamos propuestas para hacer frente al conjunto de problemas estrechamente interconectados - incluido el problema demográfico - que caracterizan dicha situación, para hacer así posible una adecuada transición a sociedades sostenibles

Mammary Gland Development as a Sensitive End Point after Acute Prenatal Exposure to an Atrazine Metabolite Mixture in Female Long-Evans Rats

BACKGROUND: Atrazine (ATR), a widely used chlorotriazine herbicide, inhibits a number of endocrine-dependent processes, including gonadotrophin surges and mammary gland development in rats. Chlorotriazine herbicides are rapidly metabolized in plants and animals to form a group of metabolites that are detected both in the environment and in exposed animals. The extent to which these metabolites are responsible directly for the observed health effects is not understood. OBJECTIVES: Our goal was to determine if a mixture of ATR metabolites, in proportions found in the environment, might produce developmental effects in Long-Evans rats following exposure late in pregnancy. METHODS: We administered an ATR metabolite mixture (AMM) containing ATR, hydroxyatrazine, diaminochlorotriazine, deethylatrazine, and deisopropylatrazine orally to pregnant Long-Evans rats at 0.09, 0.87, or 8.73 mg/kg body weight (bw)/day, on gestation days 15–19, using 0 and 100 mg ATR/kg bw/day as negative and positive controls, respectively. RESULTS: We observed no significant effect of acute AMM exposure on body weight gain in dams during the dosing period, weight loss in pups on postnatal day (PND)4, or pubertal timing, as is seen with ATR alone. However, as with ATR, we detected delayed mammary gland development, evaluated by whole mount analysis, as early as PND4 in all treatment groups. CONCLUSIONS: Our data suggest that acute exposure to AMM at levels as low as 0.09 mg/kg bw during late pregnancy causes persistent alterations in mammary gland development of female offspring, and that these effects do not appear to be related to bw or associated with pubertal timing

MP753: The Role of Interfering Plants in Regenerating Hardwood Stands of Northeastern North America

An annotated bibliography for American beech (Fagus grandifolia Ehrh.), striped maple (Acer pensylvanicum L.), hobblebush (Viburnum alnifolium Marsh.), hayscented fern (Dennstaedtia punctilobula L.), New York fern (Thelypteris noveborecensis L.), bracken fern (Pteridium aquilinum (L.) Kuhn), raspberries (Rubus spp.), and pin cherry (Prunus pensylvanica L.f.). While accessible literature includes many references to these species, the information remains scattered. No one has previously consolidated the separate reports for easy reference, nor summarized the findings relative to interference with tree regeneration. This annotated bibliography serves that purpose.https://digitalcommons.library.umaine.edu/aes_miscpubs/1023/thumbnail.jp