mTOR: from growth signal integration to cancer, diabetes and ageing

In all eukaryotes, the target of rapamycin (TOR) signalling pathway couples energy and nutrient abundance to the execution of cell growth and division, owing to the ability of TOR protein kinase to simultaneously sense energy, nutrients and stress and, in metazoans, growth factors. Mammalian TOR complex 1 (mTORC1) and mTORC2 exert their actions by regulating other important kinases, such as S6 kinase (S6K) and Akt. In the past few years, a significant advance in our understanding of the regulation and functions of mTOR has revealed the crucial involvement of this signalling pathway in the onset and progression of diabetes, cancer and ageing.National Institutes of Health (U.S.)Howard Hughes Medical InstituteWhitehead Institute for Biomedical ResearchJane Coffin Childs Memorial Fund for Medical Research (Postdoctoral Fellowship)Human Frontier Science Program (Strasbourg, France

Effects of testicular microlithiasis on Doppler parameters: report of three cases

BACKGROUND: Testicular microlithiasis is a rare, usually asymptomatic, non-progressive disease of the testes associated with various genetic anomalies, infertility and testicular tumors. According to our literature search, there is no specific data about Doppler findings in this disease. CASE PRESENTATION: Doppler findings of three cases of testicular microlithiasis during last two years in our institution are presented. CONCLUSIONS: Although our hypothesis was to find increased Doppler parameters due to intratesticular arterial compression, our findings suggest that there are no Doppler findings specific to testicular microlithiasis

Retention Time Variability as a Mechanism for Animal Mediated Long-Distance Dispersal

Long-distance dispersal (LDD) events, although rare for most plant species, can strongly influence population and community dynamics. Animals function as a key biotic vector of seeds and thus, a mechanistic and quantitative understanding of how individual animal behaviors scale to dispersal patterns at different spatial scales is a question of critical importance from both basic and applied perspectives. Using a diffusion-theory based analytical approach for a wide range of animal movement and seed transportation patterns, we show that the scale (a measure of local dispersal) of the seed dispersal kernel increases with the organisms' rate of movement and mean seed retention time. We reveal that variations in seed retention time is a key determinant of various measures of LDD such as kurtosis (or shape) of the kernel, thinkness of tails and the absolute number of seeds falling beyond a threshold distance. Using empirical data sets of frugivores, we illustrate the importance of variability in retention times for predicting the key disperser species that influence LDD. Our study makes testable predictions linking animal movement behaviors and gut retention times to dispersal patterns and, more generally, highlights the potential importance of animal behavioral variability for the LDD of seeds

Parrots Eat Nutritious Foods despite Toxins

Generalist herbivores are challenged not only by the low nitrogen and high indigestibility of their plant foods, but also by physical and chemical defenses of plants. This study investigated the foods of wild parrots in the Peruvian Amazon and asked whether these foods contain dietary components that are limiting for generalist herbivores (protein, lipids, minerals) and in what quantity; whether parrots chose foods based on nutrient content; and whether parrots avoid plants that are chemically defended.We made 224 field observations of free-ranging parrots of 17 species in 8 genera foraging on 102 species of trees in an undisturbed tropical rainforest, in two dry seasons (July-August 1992-1993) and one wet season (January-February1994). We performed laboratory analyses of parts of plants eaten and not eaten by parrots and brine shrimp assays of toxicity as a proxy for vertebrates. Parrots ate seeds, fruits, flowers, leaves, bark, and insect larvae, but up to 70% of their diet comprised seeds of many species of tropical trees, in various stages of ripeness. Plant parts eaten by parrots were rich in protein, lipid, and essential minerals, as well as potentially toxic chemicals. Seeds were higher than other plant materials in protein and lipid and lower in fiber. Large macaws of three species ate foods higher in protein and lipids and lower in fiber compared to plant parts available but not eaten. Macaws ate foods that were lower in phenolic compounds than foods they avoided. Nevertheless, foods eaten by macaws contained measurable levels of toxicity. Macaws did not appear to make dietary selections based on mineral content.Parrots represent a remarkable example of a generalist herbivore that consumes seeds destructively despite plant chemical defenses. With the ability to eat toxic foods, rainforest-dwelling parrots exploited a diversity of nutritious foods, even in the dry season when food was scarce for other frugivores and granivores

Male-like sexual behavior of female mouse lacking fucose mutarotase

<p>Abstract</p> <p>Background</p> <p>Mutarotases are recently characterized family of enzymes that are involved in the anomeric conversions of monosaccharides. The mammalian fucose mutarotase (FucM) was reported in cultured cells to facilitate fucose utilization and incorporation into protein by glycosylation. However, the role of this enzyme in animal has not been elucidated.</p> <p>Results</p> <p>We generated a mutant mouse specifically lacking the fucose mutarotase (FucM) gene. The <it>FucM </it>knockout mice displayed an abnormal sexual receptivity with a drastic reduction in lordosis score, although the animals were fertile due to a rare and forced intromission by a typical male. We examined the anteroventral periventricular nucleus (AVPv) of the preoptic region in brain and found that the mutant females showed a reduction in tyrosine hydoxylase positive neurons compared to that of a normal female. Furthermore, the mutant females exhibited a masculine behavior, such as mounting to a normal female partner as well as showing a preference to female urine. We found a reduction of fucosylated serum alpha-fetoprotein (AFP) in a mutant embryo relative to that of a wild-type embryo.</p> <p>Conclusions</p> <p>The observation that <it>FucM</it>^-/-female mouse exhibits a phenotypic similarity to a wild-type male in terms of its sexual behavior appears to be due to the neurodevelopmental changes in preoptic area of mutant brain resembling a wild-type male. Since the previous studies indicate that AFP plays a role in titrating estradiol that are required to consolidate sexual preference of female mice, we speculate that the reduced level of AFP in <it>FucM</it>^-/-mouse, presumably resulting from the reduced fucosylation, is responsible for the male-like sexual behavior observed in the FucM knock-out mouse.</p

A Comprehensive DNA Barcode Library for the Looper Moths (Lepidoptera: Geometridae) of British Columbia, Canada

The construction of comprehensive reference libraries is essential to foster the development of DNA barcoding as a tool for monitoring biodiversity and detecting invasive species. The looper moths of British Columbia (BC), Canada present a challenging case for species discrimination via DNA barcoding due to their considerable diversity and limited taxonomic maturity.By analyzing specimens held in national and regional natural history collections, we assemble barcode records from representatives of 400 species from BC and surrounding provinces, territories and states. Sequence variation in the barcode region unambiguously discriminates over 93% of these 400 geometrid species. However, a final estimate of resolution success awaits detailed taxonomic analysis of 48 species where patterns of barcode variation suggest cases of cryptic species, unrecognized synonymy as well as young species.A catalog of these taxa meriting further taxonomic investigation is presented as well as the supplemental information needed to facilitate these investigations

A hierarchical algorithm for predicting the linear viscoelastic properties of polymer melts with long-chain branching

The “hierarchical model” proposed earlier [Larson in Macromolecules 34:4556–4571, 2001] is herein modified by inclusion of early time fluctuations and other refinements drawn from the theories of Milner and McLeish for more quantitative prediction. The hierarchical model predictions are then compared with experimental linear viscoelastic data of well-defined long chain branched 1,4-polybutadienes and 1,4-polyisoprenes using a single set of parameter values for each polymer, which are obtained from experimental data for monodisperse linear and star polymers. For a wide range of monodisperse branched polymer melts, the predictions of the hierarchical model for monodisperse melts are very similar to those of the Milner–McLeish theories, and agree well with experimental data for many, but not all, of the branched polymer samples. Since the modified hierarchical model accounts for arbitrary polydispersity in molecular weight and branching distributions, which is not accounted for in the Milner–McLeish theories, the hierarchical algorithm is a promising one for predicting the relaxation of general mixtures of branched polymers.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47217/1/397_2004_Article_415.pd

Ecological Niche Modelling and nDNA Sequencing Support a New, Morphologically Cryptic Beetle Species Unveiled by DNA Barcoding

DNA sequencing techniques used to estimate biodiversity, such as DNA barcoding, may reveal cryptic species. However, disagreements between barcoding and morphological data have already led to controversy. Species delimitation should therefore not be based on mtDNA alone. Here, we explore the use of nDNA and bioclimatic modelling in a new species of aquatic beetle revealed by mtDNA sequence data. The aquatic beetle fauna of Australia is characterised by high degrees of endemism, including local radiations such as the genus Antiporus. Antiporus femoralis was previously considered to exist in two disjunct, but morphologically indistinguishable populations in south-western and south-eastern Australia. We constructed a phylogeny of Antiporus and detected a deep split between these populations. Diagnostic characters from the highly variable nuclear protein encoding arginine kinase gene confirmed the presence of two isolated populations. We then used ecological niche modelling to examine the climatic niche characteristics of the two populations. All results support the status of the two populations as distinct species. We describe the south-western species as Antiporus occidentalis sp.n. In addition to nDNA sequence data and extended use of mitochondrial sequences, ecological niche modelling has great potential for delineating morphologically cryptic species

A randomized, controlled trial of 3.0 mg of liraglutide in weight management

BACKGROUND Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagonlike peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, injected subcutaneously. METHODS We conducted a 56-week, double-blind trial involving 3731 patients who did not have type 2 diabetes and who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension. We randomly assigned patients in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. The coprimary end points were the change in body weight and the proportions of patients losing at least 5% and more than 10% of their initial body weight. RESULTS At baseline, the mean (±SD) age of the patients was 45.1±12.0 years, the mean weight was 106.2±21.4 kg, and the mean BMI was 38.3±6.4; a total of 78.5% of the patients were women and 61.2% had prediabetes. At week 56, patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg (a difference of -5.6 kg; 95% confidence interval, -6.0 to -5.1; P&lt;0.001, with last-observation-carried-forward imputation). A total of 63.2% of the patients in the liraglutide group as compared with 27.1% in the placebo group lost at least 5% of their body weight (P&lt;0.001), and 33.1% and 10.6%, respectively, lost more than 10% of their body weight (P&lt;0.001). The most frequently reported adverse events with liraglutide were mild or moderate nausea and diarrhea. Serious events occurred in 6.2% of the patients in the liraglutide group and in 5.0% of the patients in the placebo group. CONCLUSIONS In this study, 3.0 mg of liraglutide, as an adjunct to diet and exercise, was associated with reduced body weight and improved metabolic control. (Funded by Novo Nordisk; SCALE Obesity and Prediabetes NN8022-1839 ClinicalTrials.gov number, NCT01272219.)