Significant Species Differences Research Articles

The Phospholipase D2 Knock Out Mouse Has Ectopic Purkinje Cells and Suffers from Early Adult-Onset Anosmia.

Phospholipase D2 (PLD2) is an enzyme that produces phosphatidic acid (PA), a lipid messenger molecule involved in a number of cellular events including, through its membrane curvature properties, endocytosis. The PLD2 knock out (PLD2KO) mouse has been previously reported to be protected from insult in a model of Alzheimer's disease. We have further analysed a PLD2KO mouse using mass spectrophotometry of its lipids and found significant differences in PA species throughout its brain. We have examined the expression pattern of PLD2 which allowed us to define which region of the brain to analyse for defect, notably PLD2 was not detected in glial-rich regions. The expression pattern lead us to specifically examine the mitral cells of olfactory bulbs, the Cornus Amonis (CA) regions of the hippocampus and the Purkinje cells of the cerebellum. We find that the change to longer PA species correlates with subtle architectural defect in the cerebellum, exemplified by ectopic Purkinje cells and an adult-onset deficit of olfaction. These observations draw parallels to defects in the reelin heterozygote as well as the effect of high fat diet on olfaction.

Comprehensive evaluation of liver microsomal cytochrome P450 3A (CYP3A) inhibition: comparison of cynomolgus monkey and human

1. Members of the cytochrome P450 3A (CYP3A) subfamily metabolize numerous compounds and serve as the loci of drug–drug interactions (DDIs). Because of high amino acid sequence identity with human CYP3A, the cynomolgus monkey has been proposed as a model species to support DDI risk assessment.2. Therefore, the objective of this study was to evaluate 35 known inhibitors of human CYP3A using human (HLM) and cynomolgus monkey (CLM) liver microsomes. Midazolam was employed as substrate to generate IC50 values (concentration of inhibitor rendering 50% inhibition) in the absence and presence of a preincubation (30 mins) with NADPH.3. In the absence of preincubation, the IC50 values generated with CLM were similar to those obtained with HLM (86% within 2-fold; 100% within 3-fold difference). However, significant differences (up to 48-fold) in preincubation IC50 were observed with 17% of the compounds (raloxifene, bergamottin, nicardipine, mibefradil, ritonavir, and diltiazem).4. Our results indicate that in most cases the cynomolgus monkey can be a viable DDI model. However, significant species differences in time-dependent CYP3A inhibition can be observed for some compounds. In the case of raloxifene, such a difference can be ascribed to a specific CYP3A4 amino acid residue.

Metabolic Activation of Rhein: Insights into the Potential Toxicity Induced by Rhein-Containing Herbs

Rhein is a major component of the many medicinal herbs such as rhubarb. Despite wide use, intoxication cases associated with rhein-containing herbs are often reported. The present work aimed to investigate if rhein was subject to metabolic activation leading to toxicity. Upon incubations with different species of liver microsomes, three monoglucuronides were identified, corresponding to two hydroxyl glucuronides and one acyl glucuronide via the carboxyl group, respectively. Further study revealed that rhein acyl glucuronide was chemically reactive, and showed cytotoxicity toward hepatocarcinoma cells. In addition, significant species differences in glucuronidation of rhein were observed between laboratory animals and humans. Reaction phenotyping experiments demonstrated that rhein acyl glucuronide was catalyzed predominantly by uridine 5'-diphospho-glucuronosyltransferase 1A1, 1A9, and 2B7. Taken together, the present study confirmed that rhein could be metabolically activated via the formation of acyl glucuronide, especially in human.

The oxytocin receptor gene, an integral piece of the evolution of Canis familaris from Canis lupus

Previous research in canids has revealed both group (dog versus wolf) and individual differences in object choice task (OCT) performance. These differences might be explained by variation in the oxytocin receptor (OXTR) gene, as intranasally administered oxytocin has recently been shown to improve performance on this task by domestic dogs. This study looked at microsatellites at various distances from the OXTR gene to determine whether there was an association between this gene and: i) species (dog/wolf) and ii) good versus bad OCT performers. Ten primer sets were designed to amplify 10 microsatellites that were identified at various distances from the canine OXTR gene. We used 94 (52 males, 42 females) blood samples from shelter dogs, 75 (33 males, 42 females) saliva samples from pet dogs and 12 (6 males, 6 females) captive wolf saliva samples to carry out our analyses. Significant species differences were found in the two markers closest to the OXTR gene, suggesting that this gene may have played an important part in the domestic dogs’ evolution from the wolf. However, no significant, meaningful differences were found in microsatellites between good versus bad OCT performers, which suggests that other factors, such as different training and socialisation experiences, probably impacted task performance.

Optimizing the translational value of animal models of glomerulonephritis: insights from recent murine prototypes.

Animal models are indispensable for the study of glomerulonephritis, a group of diseases that destroy kidneys but for which specific therapies do not yet exist. Novel interventions are urgently needed, but their rational design requires suitable in vivo platforms to identify and test new candidates. Animal models can recreate the complex immunologic microenvironments that foster human autoimmunity and nephritis and provide access to tissue compartments not readily examined in patients. Study of rat Heymann nephritis identified fundamental disease mechanisms that ultimately revolutionized our understanding of human membranous nephropathy. Significant species differences in expression of a major target antigen, however, and lack of spontaneous autoimmunity in animals remain roadblocks to full exploitation of preclinical models in this disease. For several glomerulonephritides, humanized models have been developed to circumvent cross-species barriers and to study the effects of human genetic risk variants. Herein we review humanized mouse prototypes that provide fresh insight into mediators of IgA nephropathy and origins of antiglomerular basement membrane nephritis and Goodpasture's disease, as well as a means to test novel therapies for ANCA vasculitis. Additional and refined model systems are needed to mirror the full spectrum of human disease in a genetically diverse population, to facilitate development of patient-specific interventions, to determine the origin of nephritogenic autoimmunity, and to define the role of environmental exposures in disease initiation and relapse.

A robust (re-)annotation approach to generate unbiased mapping references for RNA-seq-based analyses of differential expression across closely related species.

BackgroundRNA-seq based on short reads generated by next generation sequencing technologies has become the main approach to study differential gene expression. Until now, the main applications of this technique have been to study the variation of gene expression in a whole organism, tissue or cell type under different conditions or at different developmental stages. However, RNA-seq also has a great potential to be used in evolutionary studies to investigate gene expression divergence in closely related species.ResultsWe show that the published genomes and annotations of the three closely related Drosophila species D. melanogaster, D. simulans and D. mauritiana have limitations for inter-specific gene expression studies. This is due to missing gene models in at least one of the genome annotations, unclear orthology assignments and significant gene length differences in the different species. A comprehensive evaluation of four statistical frameworks (DESeq2, DESeq2 with length correction, RPKM-limma and RPKM-voom-limma) shows that none of these methods sufficiently accounts for inter-specific gene length differences, which inevitably results in false positive candidate genes. We propose that published reference genomes should be re-annotated before using them as references for RNA-seq experiments to include as many genes as possible and to account for a potential length bias. We present a straight-forward reciprocal re-annotation pipeline that allows to reliably compare the expression for nearly all genes annotated in D. melanogaster.ConclusionsWe conclude that our reciprocal re-annotation of previously published genomes facilitates the analysis of significantly more genes in an inter-specific differential gene expression study. We propose that the established pipeline can easily be applied to re-annotate other genomes of closely related animals and plants to improve comparative expression analyses.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2646-x) contains supplementary material, which is available to authorized users.

Species differences in caffeine metabolism in liver microsomes of rats and mice

Caffeine and its metabolic products play an important role in clinical applications. An ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF MS/MS) method was applied to systemically study the caffeine metabolism in liver microsomes of rats and mice, and comprehensively evaluate caffeine metabolites in vitro and metabolism differences between species. The caffeine metabolites and metabolism differences between species in liver microsomes of rats and mice were analyzed by UPLC-Q-TOF-MS/MS high resolution mass spectrometry system and metabolitepolite software. The results showed that in addition to the demethylated and oxidized products in previous analysis, methylated, double oxidized, dehydrated and decarbonylated metabolites were also found in caffeine metabolism in liver microsomes of rats and mice, with significant difference in metabolism in vitro between rats and mice. The demethylated metabolite M2(C7H8N4O2) and decarbonylated metabolite M6(C7H10N4) in metabolism in vitro of mice were not found in rats, and the in vitro metabolite M7(C8H12N4O5) in rats were not found in mice. There was significant species difference in caffeine metabolism in vitro between rats and mice, providing important reference value for the further metabolism study and safety evaluation of caffeine.

Diurnal periodicity of conidia of aquatic hyphomycetes in water and entrapment on latex-coated slides in two South Indian streams

ABSTRACTAquatic hyphomycete conidial trapping efficiency by the banyan (F. benghalensis L.) latex-coated glass slides was tested diurnally (3 h intervals) in the Western Ghats (Sampaje) and west coast (Konaje) streams in relation to abiotic factors (humidity, air temperature and water temperature). The conidial trapping efficiency of latex-coated slides was compared with plain glass slides and drift conidia in water. Three methods of assessment showed higher species richness, conidial richness and diversity in Sampaje than in Konaje stream. In both streams, species richness, conidial richness and diversity in latex-coated slides were the highest followed by conidia in water and plain slides. Three-way ANOVA revealed significant differences in overall species and conidial richness between the streams, sampling methods and time of sampling (p < 0.001). Multiple comparisons by Holm–Sidak test revealed significant differences in overall species and conidial richness between Sampaje and Konaje (p < 0.001); latex-coated slides and plain slides (p < 0.001); latex-coated slides and water filtration (p < 0.001); plain slides and water filtration (p < 0.001). Total species, total conidia and diversity assessed by the three methods peaked during 12 am–3 am in Sampaje stream, while during 3 am–6 am in Konaje stream. Cooler conditions due to relatively low water temperature favoured higher diversity of aquatic hyphomycetes in Sampaje than in Konaje stream. The three methods employed in the present study were not biased towards scolecoid or stauroid conidia. The top five species in both streams was composed of both types of conidia corroborating earlier annual or biannual studies in Konaje and Sampaje streams. Thus, assessment of population of aquatic hyphomycetes using banyan latex-coated slides will be advantageous over plain slides and drift conidia in streams.

Investigation of Metabolite Profile of YM758, a Novel If Channel Inhibitor.

BackgroundYM758 monophosphate is a novel If channel inhibitor that has an inhibitory action for If current and shows a strong and specific activity, selectively lowering the heart rate and decreasing oxygen consumption by heart muscle.ObjectivesThe objectives of the current study were to investigate the in vivo metabolic profiles of YM758 in mice, rats, rabbits, dogs, and monkeys and to elucidate the structures of YM758 metabolites.MethodsBiological samples were analyzed by liquid chromatography hyphenated with a radiometric detection system and liquid chromatography coupled with a mass spectrometer to clarify their metabolic patterns. To elucidate their structures, metabolites were isolated and analyzed by mass spectrometry and nuclear magnetic resonance spectroscopy.ResultsOur results from in vivo metabolic profiling in humans and animals indicated there is no significant species difference in the metabolism of YM758, and the metabolic pathways of YM758 are considered to be oxidation, hydration, and demethylation followed by sulfate or glucuronide conjugation.

Expression of functional cannabinoid CB2 receptor in VTA dopamine neurons in rats.

We have recently reported the expression of functional cannabinoid CB2 receptors (CB2 Rs) in midbrain dopamine (DA) neurons in mice. However, little is known whether CB2 Rs are similarly expressed in rat brain because significant species differences in CB2 R structures and expression are found. In situ hybridization and immunohistochemical assays detected CB2 gene and receptors in DA neurons of the ventral tegmental area (VTA), which was up-regulated in cocaine self-administration rats. Electrophysiological studies demonstrated that activation of CB2 Rs by JWH133 inhibited VTA DA neuronal firing in single dissociated neurons. Systemic administration of JWH133 failed to alter, while local administration of JWH133 into the nucleus accumbens inhibited cocaine-enhanced extracellular DA and i.v. cocaine self-administration. This effect was blocked by AM630, a selective CB2 R antagonist. These data suggest that CB2 Rs are expressed in VTA DA neurons and functionally modulate DA neuronal activities and cocaine self-administration behavior in rats.

In vitro and In vivo effects of six Coptidis alkaloids on liver microsomes UGTs and UGT1A1 activities in rats and mice

In the present study, the effects of six Coptidis alkaloids (berberine, epiberberine, coptisine, jatrorrhizine, palmatine and magnoflorine) on liver microsomes UGTs and UGT1A1 activities in rats and mice were investigated in vitro and in vivo to study the mechanism of metabolic drug-drug interactions of Coptidis Rhizoma with other drugs. In vitro rat and mice liver microsomal incubation systems combined with UDPGA were applied, as well as mice liver microsomes after administration of six Coptidis alkaloids. 4-Nitrophenol and β-estradiol were selected as substrates to determine activities of UGTs and UGT1A1 by UV and HPLC, respectively. According to the in vitro rat study, berberine, epiberberine, coptisine and jatrorrhizine significantly inhibited rat liver microsome UGTs activity, particularly epiberberine showed the strongest inhibition. UGT1A1 activity was lowly inhibited by jatrorrhizine, with IC₅₀ at about 227 μmol•L⁻¹, whereas coptisine and magnoflorine significantly activated UGT1A1. According to the in vitro mice study, berberine, coptisine, jatrorrhizine and palmatine significantly inhibited mice liver microsome UGTs activity, and the six alkaloids all significantly activated UGT1A1. According to the in vivo mice study, UGTs activity was significantly activated only in berberine group, while UGT1A1 activity was significantly activated only in jatrorrhizine group. In conclusion, the effects of Coptidis alkaloids on UGT activity showed significant differences in species and between in vitro and in vivo. Meanwhile, the changes in structures of Coptidis alkaloids also have a big impact on UGT activity, which may be one of the causes for the drug-drug interactions between Coptidis Rhizoma and other drugs.

Prostanoid receptors mediating contraction in rat, macaque and human bladder smooth muscle in vitro

Selective prostaglandin EP1 antagonists have been suggested for the treatment of bladder dysfunction. This study assessed the contractile prostanoid receptor subtypes in human and non-human bladder in vitro. Classical tissue bath studies were conducted using bladder strips exposed to prostanoid agonists and antagonists. Prostaglandin E2 (PGE2) contracted rat, macaque and human bladder smooth muscle strips (pEC50 7.91±0.06 (n=7), 6.40±0.13 (n=7), and 6.07±0.11 (n=5), respectively). The EP1 receptor antagonist, PF2907617 (300nM), caused a rightward shift of the PGE2 concentration–response curve in the rat bladder only (pKB 8.40±0.15, n=3). PGE2 responses in rat and macaque bladders, but not human, were antagonised by the EP3 antagonist CJ24979 (1µM). Sulprostone, a mixed EP1/EP3/FP receptor agonist, induced potent contractions of rat bladder muscle (pEC50 7.94±0.31, n=6). The FP receptor agonist, prostaglandin F2α (PGF2α), induced bladder contraction in all species tested, but with a lower potency in rat. The selective FP receptor agonist latanoprost caused potent contractions of macaque and human bladder strips only. SQ29548, a selective TP antagonist, and GW848687X, a mixed EP1/TP antagonist caused rightward shifts of the concentration–response curves to the selective TP agonist, U46619 (pKB estimates 8.53±0.07 and 7.56±0.06, n=3, respectively). Responses to U46619 were absent in rat preparations. These data suggest significant species differences exist in bladder contractile prostanoid receptor subtypes. We conclude that the EP1 subtype does not represent the best approach to the clinical treatment of bladder disorders targeting inhibition of smooth muscle contraction.

CACERÍA DE SUBSISTENCIA DE MAMÍFEROS EN EL SECTOR ORIENTAL DE LA RESERVA DE BIÓSFERA EL TUPARRO – VICHADA

&lt;p&gt;&lt;strong&gt;RESUMEN&lt;/strong&gt;&lt;/p&gt;&lt;p class="p2"&gt;La cacería de subsistencia ha sido una actividad de vital importancia para las comunidades indígenas como fuente de proteína y venta. Se caracterizó la cacería de subsistencia realizada por comunidades de las etnias Piaroa y Curripaco presentes en la Reserva de Biosfera el Tuparro, por medio de registros de caza durante nueve meses de estudio. Se encontró que no hay diferencias significativas en cuanto a especies y número de individuos cazados entre las dos etnias, siendo Artiodactyla y Rodentia los órdenes con mayor aporte respecto al número de individuos, biomasa y riqueza de especies, lo cual fue similar a otros estudios realizados en el Neotrópico. Los Piaroa cazan más frecuentemente cuando los estudiantes llegan de la ciudad al resguardo, mientras que los Curripaco lo hacen para las reuniones evangélicas. El arte de caza más usado por las comunidades de las dos etnias fue la escopeta. Las etnias estudiadas tienen sus zonas de caza en la Reserva de Biósfera El Tuparro, y en ellas, los Curripaco están aprovechando directamente los recursos de su zona núcleo del Parque Nacional Natural El Tuparro.&lt;/p&gt;&lt;p class="p2"&gt;&lt;strong&gt;ABSTRACT&lt;/strong&gt;&lt;/p&gt;&lt;p class="p2"&gt;Subsistence hunting has been an activity of vital importance to indigenous communities as a source of protein and sale. We characterized subsistence hunting by Curripaco and Piaroa ethnic groups present in the Tuparro Biosphere Reserve, through hunting records over nine months of study. We found no significant differences in species and number of individuals hunted by the two ethnic groups. The orders Rodentia and Artiodactyla contributed the most in terms of number of individuals, biomass and species richness, which was similar to studies to the Neotropics. The Piaroa hunt more frequently when students return to the community lands from the city, while the Curripaco do so for religious gatherings. The hunting method used most often by both ethnic groups was the shotgun. The hunting areas used by ethnic groups are within the RBT, and the Curripaco are utilizing the resources of the Tuparro Natural National Park, the core area.&lt;/p&gt;&lt;p class="p3"&gt; &lt;/p&gt;

No up-regulation of the phosphatidylethanolamine N-methyltransferase pathway and choline production by sex hormones in cats.

BackgroundFeline hepatic lipidosis (FHL) is a common cholestatic disease affecting cats of any breed, age and sex. Both choline deficiency and low hepatic phosphatidylethanolamine N-methyltransferase (PEMT) activity are associated with hepatic lipidosis (HL) in humans, mice and rats. The PEMT expression is known to be upregulated by oestrogens, protecting the females in these species from the development of HL when exposed to choline deficient diets. The aim of the present study was to evaluate the influence of sex hormones on choline synthesis via the PEMT pathway in healthy male and female cats before and after spaying/neutering, when fed a diet with recommended dietary choline content.ResultsFrom six female and six male cats PEMT activity was assayed directly in liver biopsies taken before and after spaying/neutering, and assessed indirectly by analyses of PEMT–specific hepatic phosphatidylcholine (PC) species and plasma choline levels. Hepatic PEMT activity did not differ between intact female and male cats and no changes upon spaying/neutering were observed. Likewise, no significant differences in liver PC content and PEMT-specific polyunsaturated PC species were found between the sexes and before or after spaying/neutering.ConclusionThese results suggest that choline synthesis in cats differs from what is observed in humans, mice and rats. The lack of evident influence of sex hormones on the PEMT pathway makes it unlikely that spaying/neutering predisposes cats for HL by causing PC deficiency as suggested in other species.

Use of physiologically based kinetic (PBK) modeling to study interindividual human variation and species differences in plasma concentrations of quercetin and its metabolites

Biological activities of flavonoids in vivo ultimately depend on the systemic bioavailability of the aglycones and their metabolites. We aimed to develop physiologically based kinetic (PBK) models to predict plasma concentrations of the flavonoid quercetin and its metabolites in individual human subjects and to define species differences compared with male rat. The human models were developed based on in vitro metabolic parameters derived from incubations with pooled and 20 individual human tissue fractions and by fitting kinetic parameters to available in vivo data. The outcomes obtained were compared to a previously developed model for quercetin and its metabolites formation in male rat. Quercetin-3′-O-glucuronide was predicted to be the major circulating metabolite in 19 out of 20 individuals, while in male rat di- and tri-conjugates of quercetin containing a glucuronic acid, sulfate and/or methyl moieties are the major metabolites. Significant species differences occur in major circulating metabolites of quercetin suggesting that rat is not an adequate model to study effects of quercetin in man. The defined PBK models can be used to guide the experimental design of in vitro experiments with flavonoids, especially to better take into account the relevance of metabolism and the contribution of metabolites to the biological activity in humans.

The different metabolism of morusin in various species and its potent inhibition against UDP-glucuronosyltransferase (UGT) and cytochrome p450 (CYP450) enzymes

1. The aim of this study was to investigate the inhibitory effect of morusin on Glucuronosyltransferase (UGT) isoforms and cytochrome P450 enzymes (CYP450s). We also investigated the metabolism of morusin in human, rat, dog, monkey, and minipig liver microsomes.2. 100 μM of morusin exhibited strong inhibition on all UGTs and CYP450s. The half inhibition concentration (IC50) values for CYP3A4, CYP1A2, CYP2C9, CYP2E1, UGT1A6, UGT1A7, and UGT1A8 were 2.13, 1.27, 3.18, 9.28, 4.23, 0.98, and 3.00 μM, and the inhibition kinetic parameters (Ki) were 1.34, 1.16, 2.98, 6.23, 4.09, 0.62, and 2.11 μM, respectively.3. Metabolism of morusin exhibited significant species differences. The quantities of M1 from minipig, monkey, dog, and rat were 7.8, 11.9, 2.0, and 6.3-fold of human levels. The Km values in HLMs, RLMs, MLMs, DLMs, and PLMs were 7.84, 22.77, 14.32, 9.13, and 22.83 μM, and Vmax for these species were 0.09, 1.23, 1.43, 0.15, and 0.75 nmol/min/mg, respectively. CLint (intrinsic clearance) values (Vmax/Km) for morusin obeyed the following order: monkey > rat > minipig > dog > human. CLH (hepatic clearance) values for humans, dogs, and rats were calculated to be 8.28, 17.38, and 35.12 mL/min/kg body weight, respectively.4. This study provided vital information to understand the inhibitory potential and metabolic behavior of morusin among various species.

Implants with an Oxidized Surface Placed Predominately in Soft Bone Quality and Subjected to Immediate Occlusal Loading: Results from an 11-Year Clinical Follow-Up.

The purpose of this clinical follow-up was to document the 11-year outcome of implants with a moderately rough oxidized surface subjected to immediate occlusal loading. Twenty-six of 38 patients enrolled in a 5-year prospective study were available for this follow-up analysis, with 33 restorations supported by 66 slightly tapered implants (Brånemark System MkIV, Nobel Biocare, Gothenburg, Sweden). The majority of implants were placed in posterior regions (88%) and into soft bone (76%). Parameters included cumulative survival rate (CSR), radiographic marginal bone level, bleeding on probing (BOP), intrasulcular counts of perio-pathogenic markers (DNA probes), and total bacterial load (TBL). The CSR was 97.1% at 11.2 years mean follow-up. Mean marginal bone remodeling was 0.47 mm (SD 1.09, n = 65) from 1 year postplacement to 11-year follow-up. BOP was absent at most sites (63.6%). No statistically significant differences in TBL or perio-pathogenic marker species were observed at implants and teeth. The results of the present follow-up show high long-term survival, stable marginal bone levels, and soft tissue outcomes of oxidized surface implants placed predominately in posterior regions and soft bone. The quantity and quality of intrasulcular microbiota were comparable at implants and teeth.

Mechanistic insights revealed by lipid profiling in monogenic insulin resistance syndromes.

BackgroundEvidence from several recent metabolomic studies suggests that increased concentrations of triacylglycerols with shorter (14–16 carbon atoms), saturated fatty acids are associated with insulin resistance and the risk of type 2 diabetes. Although causality cannot be inferred from association studies, patients in whom the primary cause of insulin resistance can be genetically defined offer unique opportunities to address this challenge.MethodsWe compared metabolite profiles in patients with congenital lipodystrophy or loss-of-function insulin resistance (INSR gene) mutations with healthy controls.ResultsThe absence of significant differences in triacylglycerol species in the INSR group suggest that changes previously observed in epidemiological studies are not purely a consequence of insulin resistance. The presence of triacylglycerols with lower carbon numbers and high saturation in patients with lipodystrophy suggests that these metabolite changes may be associated with primary adipose tissue dysfunction. The observed pattern of triacylglycerol species is indicative of increased de novo lipogenesis in the liver. To test this we investigated the distribution of these triacylglycerols in lipoprotein fractions using size exclusion chromatography prior to mass spectrometry. This associated these triacylglycerols with very low-density lipoprotein particles, and hence release of triacylglycerols into the blood from the liver. To test further the hepatic origin of these triacylglycerols we induced de novo lipogenesis in the mouse, comparing ob/ob and wild-type mice on a chow or high fat diet, confirming that de novo lipogenesis induced an increase in relatively shorter, more saturated fatty acids.ConclusionsOverall, these studies highlight hepatic de novo lipogenesis in the pathogenesis of metabolic dyslipidaemia in states where energy intake exceeds the capacity of adipose tissue.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-015-0179-6) contains supplementary material, which is available to authorized users.

Concise Review: Cardiac Disease Modeling Using Induced Pluripotent Stem Cells.

Genetic cardiac diseases are major causes of morbidity and mortality. Although animal models have been created to provide some useful insights into the pathogenesis of genetic cardiac diseases, the significant species differences and the lack of genetic information for complex genetic diseases markedly attenuate the application values of such data. Generation of induced pluripotent stem cells (iPSCs) from patient-specific specimens and subsequent derivation of cardiomyocytes offer novel avenues to study the mechanisms underlying cardiac diseases, to identify new causative genes, and to provide insights into the disease aetiology. In recent years, the list of human iPSC-based models for genetic cardiac diseases has been expanding rapidly, although there are still remaining concerns on the level of functionality of iPSC-derived cardiomyocytes and their ability to be used for modeling complex cardiac diseases in adults. This review focuses on the development of cardiomyocyte induction from pluripotent stem cells, the recent progress in heart disease modeling using iPSC-derived cardiomyocytes, and the challenges associated with understanding complex genetic diseases. To address these issues, we examine the similarity between iPSC-derived cardiomyocytes and their ex vivo counterparts and how this relates to the method used to differentiate the pluripotent stem cells into a cardiomyocyte phenotype. We progress to examine categories of congenital cardiac abnormalities that are suitable for iPSC-based disease modeling.

How important is dead wood for woodpeckers foraging in eastern North American boreal forests?

Dead and decaying trees may be a limited resource for woodpeckers in managed forests, especially for species that rely on dead wood for nesting and foraging. Whereas recent nest web studies greatly increased our understanding of nest tree use by woodpeckers, knowledge on woodpeckers foraging requirements is much less developed. We quantified and compared tree selection patterns and foraging behavior of six bark-foraging woodpeckers – downy woodpecker (Picoides pubescens), hairy woodpecker (Picoides villosus), American three-toed woodpecker (Picoides dorsalis), black-backed woodpecker (Picoides arcticus), yellow-bellied sapsucker (Sphyropicus varius) and pileated woodpecker (Dryocopus pileatus) – that co-occur in eastern boreal forests of North America. A total of 271 observation bouts and more than 600 foraging trees were recorded at three study sites characterized as mixedwood, conifer, and burn. Our results show that dead wood represents an important foraging substrate for most bark-foraging woodpeckers in Canadian eastern boreal forests. However, significant differences in individual species were found with regard to substrate use patterns, foraging behavior and associated prey. Woodpeckers were categorized according to their selection for specific stages of tree degradation, with the yellow-bellied sapsucker and the pileated woodpecker representing opposite ends of this gradient. The black-backed woodpecker showed the highest use of dead wood and was very specific in its tree selection by using mostly recently dead trees. We emphasize that providing foraging substrates for most woodpecker species not only requires maintaining dead wood but also paying heed to the underlying dynamics of dead wood (e.g. recruitment and degradation) in managed boreal forest landscapes.