N-(3-(4-Hydroxyphenyl)-propenoyl)-amino acid tryptamides as SIRT2 inhibitors

A series of N-(3-(4-hydroxyphenyl)-propenoyl)-amino acid tryptamides was based on a previously reported new SIRT2 inhibitor from our group, and it was designed to study if the molecular size of the compound could be reduced. The most potent compounds, N-(3-(4-hydroxyphenyl)-propenoyl)-2-aminoisobutyric acid tryptamide and N-(3-(4-hydroxyphenyl)-propenoyl)-L-alanine tryptamide, were equipotent, 30% smaller in molecular weight, and slightly more selective (SIRT2/SIRT1) than the parent compound.     

Reverse influence of riparian buffer width on herbivorous and predatory Hemiptera

Insects are major contributors to farmland biodiversity, and their economic roles are also diverse. Many herbivorous species are crop pests, while predatory insects have the potential to act as biological controls against pests. Overall insect diversity has declined as a result of intensified agricultural practices. Riparian buffers may support insect populations in intensively cultivated areas, but their actual impact on the balance between harmful pests and beneficial predators is not known. It can be postulated that this impact may vary depending on the characteristics and location of the riparian buffer itself. We investigated the possibility that the biotic and abiotic attributes of agricultural riparian buffers adjoining crop fields and watercourses can explain the species composition of hemipteran assemblages. In particular, we were interested in the abundances of species belonging to the genus Nabis (generalist predators) and recognized and potential pests of cereal crops. Riparian buffer width and the presence or absence of woody plants were not associated with hemipteran species turnover among riparian buffers. In contrast, differences in the degree of dominance by grasses, in plant species turnover, and in which crop plant was cultivated in the adjacent field, explained a significant proportion of the variance in hemipteran species turnover. The abundance of predatory Nabis species increased with increasing riparian buffer width, whereas the abundance of recognized and potential crop pests decreased. The reverse patterns in the predatory and herbivorous Heteroptera suggest that increasing riparian buffer width might enhance biological control by Nabis predators.     

The Klingon batbugs: Morphological adaptations in the primitive bat bugs,Bucimex chilensis and Primicimex cavernis,including updated phylogeny of Cimicidae

The Cimicidae is a family of blood‐dependent ectoparasites in which dispersion capacity is greatly associated with host movements. Bats are the ancestral and most prevalent hosts for cimicids. Cimicids have a worldwide distribution matching that of their hosts, but the global classification is incomplete, especially for species outside the most common Cimicidae taxa. In this study, we place a little‐studied cimicid species, Bucimex chilensis, within a comprehensive molecular phylogeny of Cimicidae by sequencing the genomic regions of this and other closely related species. For this study, we collected B. chilensis females from Myotis chiloensis in Tierra del Fuego, 1,300 km further south than previously known southernmost distribution boundary. We also sequenced COI regions from Primicimex cavernis, a species which together with B. chilensis comprise the entire subfamily Primiciminae. Using Bayesian posterior probability and maximum‐likelihood approaches, we found that B. chilensis and P. cavernis clustered close to each other in the molecular analyses, receiving support from similar morphological features, agreeing with the morphology‐based taxonomic placement of the two species within the subfamily Primiciminae. We also describe a previously unrecognized morphological adaptation of the tarsal structure, which allows the austral bat ectoparasite, B. chilensis, to cling on to the pelage of its known host, the Chilean myotis (Myotis chiloensis). Through a morphological study and behavioral observation, we elucidate how this tarsal structure operates, and we hypothesize that by clinging in the host pelage, B. chilensis is able to disperse effectively to new areas despite low host density. This is a unique feature shared by P. cavernis, the only other species in Primiciminae.     

Direct observation of mobility state transitions in RNA trajectories by sensitive single molecule feedback tracking

Observation and tracking of fluorescently labeled molecules and particles in living cells reveals detailed information about intracellular processes on the molecular level. Whereas light microscopic particle observation is usually limited to two-dimensional projections of short trajectory segments, we report here image-based real-time three-dimensional single particle tracking in an active feedback loop with single molecule sensitivity. We tracked particles carrying only 1–3 fluorophores deep inside living tissue with high spatio-temporal resolution. Using this approach, we succeeded to acquire trajectories containing several hundred localizations. We present statistical methods to find significant deviations from random Brownian motion in such trajectories. The analysis allowed us to directly observe transitions in the mobility of ribosomal (r)RNA and Balbiani ring (BR) messenger (m)RNA particles in living Chironomus tentans salivary gland cell nuclei. We found that BR mRNA particles displayed phases of reduced mobility, while rRNA particles showed distinct binding events in and near nucleoli.     

Hemodynamic actions and mechanisms of systemically administered α-MSH analogs in mice

α-Melanocyte-stimulating hormone (α-MSH) regulates important physiological functions including energy homeostasis and inflammation. Potent analogs of α-MSH, [Nle⁴, d-Phe⁷]-α-MSH (NDP-α-MSH) and melanotan-II (MT-II), are widely used in pharmacological studies, but the hemodynamic effects associated with their systemic administration have not been thoroughly examined. Therefore, we investigated the hemodynamic actions of these compounds in anesthetized and conscious C57Bl/6N mice using peripheral routes of administration. NDP-α-MSH and MT-II induced mild changes in blood pressure and heart rate in anesthetized mice compared to the effects observed in conscious mice, suggesting that anesthesia distorts the hemodynamic actions of α-MSH analogs. In conscious mice, NDP-α-MSH and MT-II increased blood pressure and heart rate in a dose-dependent manner, but the tachycardic effect was more prominent than the pressor effect. Pretreatment with the melanocortin (MC) 3/4 receptor antagonist SHU9119 abolished these hemodynamic effects. Furthermore, the blockade of β₁-adrenoceptors with metoprolol prevented the pressor effect and partly the tachycardic action of α-MSH analogs, while the ganglionic blocker hexamethonium abrogated completely the difference in heart rate between vehicle and α-MSH treatments. These findings suggest that the pressor effect is primarily caused by augmentation of cardiac sympathetic activity, but the tachycardic effect seems to involve withdrawal of vagal tone in addition to sympathetic activation. In conclusion, the present results indicate that systemic administration of α-MSH analogs elevates blood pressure and heart rate via activation of MC_3/4 receptor pathways. These effects and the consequent increase in cardiac workload should be taken into account when using α-MSH analogs via peripheral routes of administration.     

Dynamics and interactions of parvoviral NS1 protein in the nucleus

Nuclear positioning and dynamic interactions of viral proteins with nuclear substructures play essential roles during infection with DNA viruses. Visualization of the intranuclear interactions and motility of the parvovirus replication protein (NS1) in living cells gives insight into specific parvovirus protein-cellular structure interactions. Confocal analysis of highly synchronized infected Norden Laboratory Feline Kidney cells showed accumulation of nuclear NS1 in discrete interchromosomal foci. NS1 fused with enhanced yellow fluorescence protein (NS1-EYFP) provided a marker in live cells for dynamics of NS1 traced by photobleaching techniques. Fluorescence Recovery after Photobleaching suggested that the NS1 protein is not freely diffusing but undergoes transient interactions with nuclear compartments. Fluorescence Loss in Photobleaching demonstrated for the first time the shuttling of a parvoviral protein between the nucleus and the cytoplasm as assayed with NS1-EYFP. Finally, time-lapse imaging of infected cells revealed that the intranuclear distribution of NS1-EYFP evolves dramatically starting from the formation of NS1 foci and proceeding to a homogenous distribution extending throughout the nucleus.     

Changes in Soybean (Glycine max [L.] Merr.) Glycerolipids in Response to Water Stress

Soybean (Glycine max [L.] Merr.) plants with the first trifoliate leaf fully expanded were exposed to 4 and 8 days of water stress. Leaf water potentials dropped from −0.6 megapascal to −1.7 megapascals after 4 days of stress; then to −3.1 megapascals after 8 days without water. All of the plants recovered when rewatered. The effects of short-term drought stress on triacylglycerol, diacylglycerol, phospholipid, and galactolipid metabolism in the first trifoliate leaves was determined. Leaf triacylglycerol and diacylglycerol content increased 2-fold during the first 4 days of stress and returned to control levels 3 days after rewatering. The polar lipid fraction, which contained phospholipids and galactolipids, changed little during this time. The linolenic acid (18:3) content of the triacylglycerol and diacylglycerol increased 25% during stress and the polar lipid 18:3 content decreased 15%. The pattern of glycerolipid labeling, after applying [2-¹⁴C]acetate to intact leaves was altered by water stress. After 4 days of water stress the radioactivity of phosphatidic acid + phosphatidylinositol, phosphatidylcholine, triacylglycerol, and diacylglycerol increased between 4 and 9% (compared to control plans) while radioactivity of phosphatidylethanolamine, monogalactosyldiglyceride, and digalactosyldiglyceride decreased 2 to 11%. These data indicated that increased levels of triacylglycerol and diacylglycerol observed during water stress were attributed to de novo synthesis rather than breakdown or reutilization of existing glycerolipids and fatty acids.     

Measles Virus Antibody in Cerebrospinal Fluids from Patients with Multiple Sclerosis

A strong measles-specific gel precipitation reaction was found in the cerebrospinal fluid (C.S.F.) of two patients with multiple sclerosis (M.S.) (total of 15 tested). The serum and C.S.F. specimens from these two patients were tested for measles antibody by six assay methods. The results were compared with those obtained from serum and C.S.F. specimens of a patient with subacute sclerosing panencephalitis (S.S.P.E.). The gel precipitation line produced by the C.S.F. from the M.S. patients was identical with one of the three lines produced by the C.S.F. from the S.S.P.E. patient. The main antigenic component responsible for measles antibody appearing in the C.S.F. of the S.S.P.E. patient and the M.S. patients was also electrophoretically similar, and the corresponding antibody was associated with IgG. The serum/C.S.F. antibody titre ratios with the various assay methods used suggest that the C.S.F. antibodies are mainly to other than envelope components of measles virus. No complement-fixing antibody against 27 other viruses or Mycoplasma pneumoniae was found in the C.S.F. of the two M.S. patients.