HIV-1 protease inhibition potential of functionalized polyoxometalates

Polyoxometalates (POMs) are interesting biomedical agents due to their versatile anticancer and antiviral properties, such as remarkable anti-HIV activity. Although POMs are tunable and easily accessible inorganic drug prototypes in principle, their full potential can only be tapped by enhancing their biocompatibility, for example, through organic functionalization. We have therefore investigated the HIV-1 protease inhibition potential of functionalized Keggin- and Dawson-type POMs with organic side chains. Their inhibitory performance was furthermore compared to other POM types, and the buffer dependence of the results is discussed. In addition, chemical shift mapping NMR experiments were performed to exclude POM-substrate interactions. Whereas the introduction of organic side chains into POMs is a promising approach in principle, the influence of secondary effects on the reaction system also merits detailed investigation.     

Cancer and cardiovascular diseases nutrition knowledge and dietary intake of medical students

The aims of this study were to determine medical students' knowledge regarding the association between dietary factors and the risk of cancer and cardiovascular diseases and to investigate if this knowledge has an impact on their dietary intakes. Three hundred and ninety medical students (males and females) were included in a study and grouped according to their daily fibre and fat intakes. For diet-disease knowledge, questions from the General Nutrition Knowledge Questionnaire for Adults were used and dietary assessment was done with Food Frequency Questionnaire. The obtained results showed that the students' diet-disease knowledge was generally inadequate. Higher level of diet-disease knowledge was among those with high dietary fibre intake, with slightly better scores for dietary factors and risk for cardiovascular diseases than the risk for cancer. Better diet-disease knowledge positively correlated with higher intake of fish (p = 0.027, p = 0.001) and vegetables (p = 0.019, p = 0.001) in high fibre groups of both gender, and in females additionally with fruit intake (p = 0.038, p = 0.007). A higher dietary fibre intake among studied students seems to be a factor that ensures lower obesity rates, lower intake of energy and lower consumption of coffee, sweets and alcoholic drinks. On the basis of the results of this study, it is clear that medical schools should provide in their nutrition programs the opportunity for students to learn about their own dietary and lifestyle behaviours, in order to more knowledgably and convincingly counsel their future patients.     

Rapid Whisker Movements in Sleeping Newborn Rats

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Highlights? Whiskers twitch rapidly and asynchronously in sleeping infant rats ? Whisker twitches result from activation of dedicated whisker skeletal muscles ? Whisker twitches trigger bursts of neural activity in whisker thalamus ? Barrel cortex exhibits discrete activation during periods of twitching     

piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans

Transgenerational effects have wide-ranging implications for human health, biological adaptation, and evolution; however, their mechanisms and biology remain poorly understood. Here, we demonstrate that a germline nuclear small RNA/chromatin pathway can maintain stable inheritance for many generations when triggered by a piRNA-dependent foreign RNA response in C. elegans. Using forward genetic screens and candidate approaches, we find that a core set of nuclear RNAi and chromatin factors is required for multigenerational inheritance of environmental RNAi and piRNA silencing. These include a germline-specific nuclear Argonaute HRDE1/WAGO-9, a HP1 ortholog HPL-2, and two putative histone methyltransferases, SET-25 and SET-32. piRNAs can trigger highly stable long-term silencing lasting at least 20 generations. Once established, this long-term memory becomes independent of the piRNA trigger but remains dependent on the nuclear RNAi/chromatin pathway. Our data present a multigenerational epigenetic inheritance mechanism induced by piRNAs.     

Inherited phenotype instability of inflorescence and floral organ development in homeotic barley double mutants and its specific modification by auxin inhibitors and 2,4-D

Background and Aims Barley (Hordeum vulgare) double mutants Hv-Hd/tw₂, formed by hybridization, are characterized by inherited phenotypic instability and by several new features, such as bract/leaf-like structures, long naked gaps in the spike, and a wide spectrum of variations in the basic and ectopic flowers, which are absent in single mutants. Several of these features resemble those of mutations in auxin distribution, and thus the aim of this study was to determine whether auxin imbalances are related to phenotypic variations and instability. The effects of auxin inhibitors and 2,4-D (2,4-dichlorophenoxyacetic acid) on variation in basic and ectopic flowers were therefore examined, together with the effects of 2,4-D on spike structure.Methods The character of phenotypic instability and the effects of auxin inhibitors and 2,4-D were compared in callus cultures and intact plants of single homeotic Hv-tw₂ and Hv-Hooded/Kap (in the BKn3 gene) mutants and alternative double mutant lines: offspring from individual plants in distal hybrid generations (F₉–F₁₀) that all had the same BKn3 allele as determined by DNA sequencing. For intact plants, two auxin inhibitors, 9-hydroxyfluorene-9-carboxylic acid (HFCA) and p-chlorophenoxyisobutyric acid (PCIB), were used.Key Results Callus growth and flower/spike structures of the Hv-tw₂ mutant differed in their responses to HFCA and PCIB. An increase in normal basic flowers after exposure to auxin inhibitors and a decrease in their frequencies caused by 2,4-D were observed, and there were also modifications in the spectra of ectopic flowers, especially those with sexual organs, but the effects depended on the genotype. Exposure to 2,4-D decreased the frequency of short gaps and lodicule transformations in Hv-tw₂ and of long naked gaps in double mutants.Conclusions The effects of auxin inhibitors and 2,4-D suggest that ectopic auxin maxima or deficiencies arise in various regions of the inflorescence/flower primordia. Based on the phenotypic instability observed, definite trends in the development of ectopic flower structures may be detected, from insignificant outgrowths on awns to flowers with sterile organs. Phenotypically unstable barley double mutants provide a highly promising genetic system for the investigation of gene expression modules and trend orders.     

Ranking candidate genes in rat models of type 2 diabetes

Background  

Rat models are frequently used to find genomic regions that contribute to complex diseases, so called quantitative trait loci (QTLs). In general, the genomic regions found to be associated with a quantitative trait are rather large, covering hundreds of genes. To help selecting appropriate candidate genes from QTLs associated with type 2 diabetes models in rat, we have developed a web tool called Candidate Gene Capture (CGC), specifically adopted for this disorder.     

Increases in intracellular calcium triggered by channelrhodopsin-2 potentiate the response of metabotropic glutamate receptor mGluR7

The metabotropic glutamate receptor 7a (mGluR7a), a heptahelical Galpha(i/o)-coupled protein, has been shown to be important for presynaptic feedback inhibition at central synapses and certain forms of long term potentiation and long term depression. The intracellular C terminus of mGluR7a interacts with calmodulin in a Ca(2+)-dependent manner, and calmodulin antagonists have been found to abolish presynaptic inhibition of glutamate release in neurons and mGluR7a-induced activation of G-protein-activated inwardly rectifying K(+) channel (GIRK) channels in HEK293 cells. Here, we characterized the Ca(2+) dependence of mGluR7a signaling in Xenopus oocytes by using channelrhodopsin-2 (ChR2), a Ca(2+)-permeable, light-activated ion channel for triggering Ca(2+) influx, and a GIRK3.1/3.2 concatemer to monitor mGluR7a responses. Application of the agonist (S)-2-amino-4-phosphonobutanoic acid (l-AP4) (1-100 mum) caused a dose-dependent inward current in high K(+) solutions due to activation of GIRK channels by G-protein betagamma subunits released from mGluR7a. Elevation of intracellular free Ca(2+) by light stimulation of ChR2 markedly increased the amplitude of l-AP4 responses, and this effect was attenuated by the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxymethyl ester). l-AP4 responses were potentiated by submembranous [Ca(2+)] levels within physiological ranges and with a threshold close to resting [Ca(2+)](i) values, as determined by recording the endogenous Xenopus Ca(2+)-activated chloride conductance. Together, these results show that l-AP4-dependent mGluR7a signaling is potentiated by physiological levels of [Ca(2+)](i), consistent with a model in which presynaptic mGluR7a acts as a coincidence detector of Ca(2+) influx and glutamate release.     

Phase shift from a coral to a corallimorph-dominated reef associated with a shipwreck on Palmyra atoll

Coral reefs can undergo relatively rapid changes in the dominant biota, a phenomenon referred to as phase shift. Various reasons have been proposed to explain this phenomenon including increased human disturbance, pollution, or changes in coral reef biota that serve a major ecological function such as depletion of grazers. However, pinpointing the actual factors potentially responsible can be problematic. Here we show a phase shift from coral to the corallimorpharian Rhodactis howesii associated with a long line vessel that wrecked in 1991 on an isolated atoll (Palmyra) in the central Pacific Ocean. We documented high densities of R. howesii near the ship that progressively decreased with distance from the ship whereas R. howesii were rare to absent in other parts of the atoll. We also confirmed high densities of R. howesii around several buoys recently installed on the atoll in 2001. This is the first time that a phase shift on a coral reef has been unambiguously associated with man-made structures. This association was made, in part, because of the remoteness of Palmyra and its recent history of minimal human habitation or impact. Phase shifts can have long-term negative ramification for coral reefs, and eradication of organisms responsible for phase shifts in marine ecosystems can be difficult, particularly if such organisms cover a large area. The extensive R. howesii invasion and subsequent loss of coral reef habitat at Palmyra also highlights the importance of rapid removal of shipwrecks on corals reefs to mitigate the potential of reef overgrowth by invasives.