In vivo antihyperglycaemic and antihyperlipidemic activities and chemical constituents of Solanum anomalum

Solanum anomalum is a plant used ethnomedically for the treatment of diabetes. The study was aimed to validate ethnomedical claims in rat model and identify the likely antidiabetic compounds. Leaf extract (70–210 mg/kg/day) and fractions (140 mg/kg/day) of S. anomalum were evaluated in hyperglycaemic rats induced using alloxan for effects on blood glucose, lipids and pancreas histology. Phytochemical characterisation of isolated compounds and their identification were performed using mass spectrometry and NMR spectroscopy. Bioinformatics tool was used to predict the possible protein targets of the identified bioactive compounds. The leaf extract/fractions on administration to diabetic rats caused significant lowering of fasting blood glucose of the diabetic rats during single dose study and on repeated administration of the extract. The hydroethanolic leaf extracts also enhanced glucose utilization capacity of the diabetic rats and caused significant lowering of glycosylated hemoglobin levels and elevation of insulin levels in the serum. Furthermore, triglycerides, LDL-cholesterol, and VLDL-cholesterol levels were lowered significantly, while HDL–cholesterol levels were also elevated in the treated diabetic rats. There was absence or few pathological signs in the treated hyperglycaemic rat pancreas compared to that present in the pancreas of control group. Diosgenin, 25(R)-diosgenin-3-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranoside, uracil, thymine, 1-octacosanol, and octacosane were isolated and identified. Protein phosphatases along with secreted proteins are predicted to be the major targets of diosgenin and the diosgenin glycoside. These results suggest that the leaf extract/fractions of S. anomalum possess antidiabetic and antihyperlipidemic properties, offer protection to the pancreas and stimulate insulin secretion, which can be attributable to the activities of its phytochemical constituents

Streptococcus intermedius causing infective endocarditis and abscesses: a report of three cases and review of the literature

<p>Abstract</p> <p>Background</p> <p><it>Streptococcus intermedius </it>is a member of the Streptococcus anginosus group. Clinical disease with <it>S. intermedius </it>is characterized by abscess formation and rarely endocarditis. Identification of <it>Streptococcus intermedius </it>is difficult, leading to the development of molecular methods to more accurately identify and characterize this organism.</p> <p>Case presentation</p> <p>Over a period of 6 months we encountered three cases of invasive <it>Streptococcus intermedius </it>infection presenting as hepatic abscesses, brain abscess, and endocarditis. We confirmed our microbiologic diagnosis through 16S sequencing and found a common virulence gene in each case.</p> <p>Conclusion</p> <p>Our report illustrates three different clinical manifestations due to <it>Streptococcus intermedius </it>infection that can be encountered in healthy individuals in a community hospital setting. To our knowledge, this is the first case of <it>Streptococcus intermedius </it>endocarditis confirmed by 16S sequencing analysis. The use of molecular methods may allow a better understanding of the epidemiology and pathogenesis of this organism.</p

Harmonics of Circadian Gene Transcription in Mammals

The circadian clock is a molecular and cellular oscillator found in most mammalian tissues that regulates rhythmic physiology and behavior. Numerous investigations have addressed the contribution of circadian rhythmicity to cellular, organ, and organismal physiology. We recently developed a method to look at transcriptional oscillations with unprecedented precision and accuracy using high-density time sampling. Here, we report a comparison of oscillating transcription from mouse liver, NIH3T3, and U2OS cells. Several surprising observations resulted from this study, including a 100-fold difference in the number of cycling transcripts in autonomous cellular models of the oscillator versus tissues harvested from intact mice. Strikingly, we found two clusters of genes that cycle at the second and third harmonic of circadian rhythmicity in liver, but not cultured cells. Validation experiments show that 12-hour oscillatory transcripts occur in several other peripheral tissues as well including heart, kidney, and lungs. These harmonics are lost ex vivo, as well as under restricted feeding conditions. Taken in sum, these studies illustrate the importance of time sampling with respect to multiple testing, suggest caution in use of autonomous cellular models to study clock output, and demonstrate the existence of harmonics of circadian gene expression in the mouse

Adult Circadian Behavior in Drosophila Requires Developmental Expression of cycle, But Not period

Circadian clocks have evolved as internal time keeping mechanisms that allow anticipation of daily environmental changes and organization of a daily program of physiological and behavioral rhythms. To better examine the mechanisms underlying circadian clocks in animals and to ask whether clock gene expression and function during development affected subsequent daily time keeping in the adult, we used the genetic tools available in Drosophila to conditionally manipulate the function of the CYCLE component of the positive regulator CLOCK/CYCLE (CLK/CYC) or its negative feedback inhibitor PERIOD (PER). Differential manipulation of clock function during development and in adulthood indicated that there is no developmental requirement for either a running clock mechanism or expression of per. However, conditional suppression of CLK/CYC activity either via per over-expression or cyc depletion during metamorphosis resulted in persistent arrhythmic behavior in the adult. Two distinct mechanisms were identified that may contribute to this developmental function of CLK/CYC and both involve the ventral lateral clock neurons (LNvs) that are crucial to circadian control of locomotor behavior: (1) selective depletion of cyc expression in the LNvs resulted in abnormal peptidergic small-LNv dorsal projections, and (2) PER expression rhythms in the adult LNvs appeared to be affected by developmental inhibition of CLK/CYC activity. Given the conservation of clock genes and circuits among animals, this study provides a rationale for investigating a possible similar developmental role of the homologous mammalian CLOCK/BMAL1 complex

Dopamine Modulates the Rest Period Length without Perturbation of Its Power Law Distribution in Drosophila melanogaster

We analyzed the effects of dopamine signaling on the temporal organization of rest and activity in Drosophila melanogaster. Locomotor behaviors were recorded using a video-monitoring system, and the amounts of movements were quantified by using an image processing program. We, first, confirmed that rest bout durations followed long-tailed (i.e., power-law) distributions, whereas activity bout durations did not with a strict method described by Clauset et al. We also studied the effects of circadian rhythm and ambient temperature on rest bouts and activity bouts. The fraction of activity significantly increased during subjective day and at high temperature, but the power-law exponent of the rest bout distribution was not affected. The reduction in rest was realized by reduction in long rest bouts. The distribution of activity bouts did not change drastically under the above mentioned conditions. We then assessed the effects of dopamine. The distribution of rest bouts became less long-tailed and the time spent in activity significantly increased after the augmentation of dopamine signaling. Administration of a dopamine biosynthesis inhibitor yielded the opposite effects. However, the distribution of activity bouts did not contribute to the changes. These results suggest that the modulation of locomotor behavior by dopamine is predominantly controlled by changing the duration of rest bouts, rather than the duration of activity bouts

Trophic Shifts of a Generalist Consumer in Response to Resource Pulses

Trophic shifts of generalist consumers can have broad food-web and biodiversity consequences through altered trophic flows and vertical diversity. Previous studies have used trophic shifts as indicators of food-web responses to perturbations, such as species invasion, and spatial or temporal subsidies. Resource pulses, as a form of temporal subsidies, have been found to be quite common among various ecosystems, affecting organisms at multiple trophic levels. Although diet switching of generalist consumers in response to resource pulses is well documented, few studies have examined if the switch involves trophic shifts, and if so, the directions and magnitudes of the shifts. In this study, we used stable carbon and nitrogen isotopes with a Bayesian multi-source mixing model to estimate proportional contributions of three trophic groups (i.e. producer, consumer, and fungus-detritivore) to the diets of the White-footed mouse (Peromyscus leucopus) receiving an artificial seed pulse or a naturally-occurring cicadas pulse. Our results demonstrated that resource pulses can drive trophic shifts in the mice. Specifically, the producer contribution to the mouse diets was increased by 32% with the seed pulse at both sites examined. The consumer contribution to the mouse diets was also increased by 29% with the cicadas pulse in one of the two grids examined. However, the pattern was reversed in the second grid, with a 13% decrease in the consumer contribution with the cicadas pulse. These findings suggest that generalist consumers may play different functional roles in food webs under perturbations of resource pulses. This study provides one of the few highly quantitative descriptions on dietary and trophic shifts of a key consumer in forest food webs, which may help future studies to form specific predictions on changes in trophic interactions following resource pulses

Adult Circadian Behavior in Drosophila Requires Developmental Expression of cycle, But Not period

Circadian clocks have evolved as internal time keeping mechanisms that allow anticipation of daily environmental changes and organization of a daily program of physiological and behavioral rhythms. To better examine the mechanisms underlying circadian clocks in animals and to ask whether clock gene expression and function during development affected subsequent daily time keeping in the adult, we used the genetic tools available in Drosophila to conditionally manipulate the function of the CYCLE component of the positive regulator CLOCK/CYCLE (CLK/CYC) or its negative feedback inhibitor PERIOD (PER). Differential manipulation of clock function during development and in adulthood indicated that there is no developmental requirement for either a running clock mechanism or expression of per. However, conditional suppression of CLK/CYC activity either via per over-expression or cyc depletion during metamorphosis resulted in persistent arrhythmic behavior in the adult. Two distinct mechanisms were identified that may contribute to this developmental function of CLK/CYC and both involve the ventral lateral clock neurons (LNvs) that are crucial to circadian control of locomotor behavior: (1) selective depletion of cyc expression in the LNvs resulted in abnormal peptidergic small-LNv dorsal projections, and (2) PER expression rhythms in the adult LNvs appeared to be affected by developmental inhibition of CLK/CYC activity. Given the conservation of clock genes and circuits among animals, this study provides a rationale for investigating a possible similar developmental role of the homologous mammalian CLOCK/BMAL1 complex

Genome Features of “Dark-Fly”, a Drosophila Line Reared Long-Term in a Dark Environment

Organisms are remarkably adapted to diverse environments by specialized metabolisms, morphology, or behaviors. To address the molecular mechanisms underlying environmental adaptation, we have utilized a Drosophila melanogaster line, termed “Dark-fly”, which has been maintained in constant dark conditions for 57 years (1400 generations). We found that Dark-fly exhibited higher fecundity in dark than in light conditions, indicating that Dark-fly possesses some traits advantageous in darkness. Using next-generation sequencing technology, we determined the whole genome sequence of Dark-fly and identified approximately 220,000 single nucleotide polymorphisms (SNPs) and 4,700 insertions or deletions (InDels) in the Dark-fly genome compared to the genome of the Oregon-R-S strain, a control strain. 1.8% of SNPs were classified as non-synonymous SNPs (nsSNPs: i.e., they alter the amino acid sequence of gene products). Among them, we detected 28 nonsense mutations (i.e., they produce a stop codon in the protein sequence) in the Dark-fly genome. These included genes encoding an olfactory receptor and a light receptor. We also searched runs of homozygosity (ROH) regions as putative regions selected during the population history, and found 21 ROH regions in the Dark-fly genome. We identified 241 genes carrying nsSNPs or InDels in the ROH regions. These include a cluster of alpha-esterase genes that are involved in detoxification processes. Furthermore, analysis of structural variants in the Dark-fly genome showed the deletion of a gene related to fatty acid metabolism. Our results revealed unique features of the Dark-fly genome and provided a list of potential candidate genes involved in environmental adaptation

Integrated Operational Taxonomic Units (IOTUs) in Echolocating Bats: A Bridge between Molecular and Traditional Taxonomy

Background: Nowadays, molecular techniques are widespread tools for the identification of biological entities. However, until very few years ago, their application to taxonomy provoked intense debates between traditional and molecular taxonomists. To prevent every kind of disagreement, it is essential to standardize taxonomic definitions. Along these lines, we introduced the concept of Integrated Operational Taxonomic Unit (IOTU). IOTUs come from the concept of Operational Taxonomic Unit (OTU) and paralleled the Molecular Operational Taxonomic Unit (MOTU). The latter is largely used as a standard in many molecular-based works (even if not always explicitly formalized). However, while MOTUs are assigned solely on molecular variation criteria, IOTUs are identified from patterns of molecular variation that are supported by at least one more taxonomic characteristic. Methodology/Principal Findings: We tested the use of IOTUs on the widest DNA barcoding dataset of Italian echolocating bats species ever assembled (i.e. 31 species, 209 samples). We identified 31 molecular entities, 26 of which corresponded to the morphologically assigned species, two MOTUs and three IOTUs. Interestingly, we found three IOTUs in Myotis nattereri, one of which is a newly described lineage found only in central and southern Italy. In addition, we found a level of molecular variability within four vespertilionid species deserving further analyses. According to our scheme two of them (i.e. M. bechsteinii and Plecotus auritus) should be ranked as unconfirmed candidate species (UCS). Conclusions/Significance: From a systematic point of view, IOTUs are more informative than the general concept of OTUs and the more recent MOTUs. According to information content, IOTUs are closer to species, although it is important to underline that IOTUs are not species. Overall, the use of a more precise panel of taxonomic entities increases the clarity in the systematic field and has the potential to fill the gaps between modern and traditional taxonomy