Waves of genomic hitchhikers shed light on the evolution of gamebirds (Aves: Galliformes) : research article

Background The phylogenetic tree of Galliformes (gamebirds, including megapodes, currassows, guinea fowl, New and Old World quails, chicken, pheasants, grouse, and turkeys) has been considerably remodeled over the last decades as new data and analytical methods became available. Analyzing presence/absence patterns of retroposed elements avoids the problems of homoplastic characters inherent in other methodologies. In gamebirds, chicken repeats 1 (CR1) are the most prevalent retroposed elements, but little is known about the activity of their various subtypes over time. Ascertaining the fixation patterns of CR1 elements would help unravel the phylogeny of gamebirds and other poorly resolved avian clades. Results We analyzed 1,978 nested CR1 elements and developed a multidimensional approach taking advantage of their transposition in transposition character (TinT) to characterize the fixation patterns of all 22 known chicken CR1 subtypes. The presence/absence patterns of those elements that were active at different periods of gamebird evolution provided evidence for a clade (Cracidae + (Numididae + (Odontophoridae + Phasianidae))) not including Megapodiidae; and for Rollulus as the sister taxon of the other analyzed Phasianidae. Genomic trace sequences of the turkey genome further demonstrated that the endangered African Congo Peafowl (Afropavo congensis) is the sister taxon of the Asian Peafowl (Pavo), rejecting other predominantly morphology-based groupings, and that phasianids are monophyletic, including the sister taxa Tetraoninae and Meleagridinae. Conclusions The TinT information concerning relative fixation times of CR1 subtypes enabled us to efficiently investigate gamebird phylogeny and to reconstruct an unambiguous tree topology. This method should provide a useful tool for investigations in other taxonomic groups as well

Computational Methods in Science and Engineering : Proceedings of the Workshop SimLabs@KIT, November 29 - 30, 2010, Karlsruhe, Germany

In this proceedings volume we provide a compilation of article contributions equally covering applications from different research fields and ranging from capacity up to capability computing. Besides classical computing aspects such as parallelization, the focus of these proceedings is on multi-scale approaches and methods for tackling algorithm and data complexity. Also practical aspects regarding the usage of the HPC infrastructure and available tools and software at the SCC are presented

Dual-RNAseq Analysis Unravels Virus-Host Interactions of MetSV and Methanosarcina mazei

Methanosarcina spherical virus (MetSV), infecting Methanosarcina species, encodes 22 genes, but their role in the infection process in combination with host genes has remained unknown. To study the infection process in detail, infected and uninfected M. mazei cultures were compared using dual-RNAseq, qRT-PCRs, and transmission electron microscopy (TEM). The transcriptome analysis strongly indicates a combined role of virus and host genes in replication, virus assembly, and lysis. Thereby, 285 host and virus genes were significantly regulated. Within these 285 regulated genes, a network of the viral polymerase, MetSVORF6, MetSVORF5, MetSVORF2, and the host genes encoding NrdD, NrdG, a CDC48 family protein, and a SSB protein with a role in viral replication was postulated. Ultrastructural analysis at 180 min p.i. revealed many infected cells with virus particles randomly scattered throughout the cytoplasm or attached at the cell surface, and membrane fragments indicating cell lysis. Dual-RNAseq and qRT-PCR analyses suggested a multifactorial lysis reaction in potential connection to the regulation of a cysteine proteinase, a pirin-like protein and a HicB-solo protein. Our study's results led to the first preliminary infection model of MetSV infecting M. mazei, summarizing the key infection steps as follows: replication, assembly, and host cell lysis

Evaluation of the relationship between hyperinsulinaemia and myocardial ischaemia/reperfusion injury in a rat model of depression

Major depression is associated with medical comorbidity such as ischaemic heart disease and diabetes but the underlying pathophysiological mechanisms remain unclear. The Flinders Sensitive Line (FSL) rat is a genetic animal model of depression exhibiting features similar to those of depressed individuals. The aim of the present study was to compare the myocardial responsiveness to ischaemia-reperfusion injury and effects of ischaemic preconditioning (IPC) in hearts from FSL rats using Sprague-Dawley (SD) rats as controls and to characterize differences in glucose metabolism and insulin sensitivity between the FSL and SD rats. Hearts were perfused in a Langendorff model and subjected or not to IPC before 40 minutes of global ischaemia followed by 120 minutes of reperfusion. Myocardial infarct size was found to be significantly larger in the FSL rats (I/R: 62.4±4.2 vs. 46.9±2.9%, P<0.05) than in the SD rats. IPC reduced the infarct size (P<0.01) and improved haemodynamic function (P<0.01) in both the FSL and the SD rats. No significant difference was found in blood glucose levels between the two groups measured after 12 hours of fasting but fasting plasma insulin (70.1±8.9 vs. 40.9±4.7 pmol/l, P<0.05) and HOMA (homeostatic model assessment) index (P<0.01) were significantly higher in the FSL rats compared to the SD rats. In conclusion, FSL rats had larger infarct sizes and were found to be hyperinsulinaemic compared to SD rats but seemed to have a maintained cardioprotective mechanism against ischaemia-reperfusion injury as IPC reduced infarct size in these rats. This animal model may be useful in future studies when examining the mechanisms that contribute to the cardiovascular complications associated with depression

Retroposed Elements as Archives for the Evolutionary History of Placental Mammals

Reconstruction of the placental mammalian (eutherian) evolutionary tree has undergone diverse revisions, and numerous aspects remain hotly debated. Initial hierarchical divisions based on morphology contained many misgroupings due to features that evolved independently by similar selection processes. Molecular analyses corrected many of these misgroupings and the superordinal hierarchy of placental mammals was recently assembled into four clades. However, long or rapid evolutionary periods, as well as directional mutation pressure, can produce molecular homoplasies, similar characteristics lacking common ancestors. Retroposed elements, by contrast, integrate randomly into genomes with negligible probabilities of the same element integrating independently into orthologous positions in different species. Thus, presence/absence analyses of these elements are a superior strategy for molecular systematics. By computationally scanning more than 160,000 chromosomal loci and judiciously selecting from only phylogenetically informative retroposons for experimental high-throughput PCR applications, we recovered 28 clear, independent monophyly markers that conclusively verify the earliest divergences in placental mammalian evolution. Using tests that take into account ancestral polymorphisms, multiple long interspersed elements and long terminal repeat element insertions provide highly significant evidence for the monophyletic clades Boreotheria (synonymous with Boreoeutheria), Supraprimates (synonymous with Euarchontoglires), and Laurasiatheria. More importantly, two retropositions provide new support for a prior scenario of early mammalian evolution that places the basal placental divergence between Xenarthra and Epitheria, the latter comprising all remaining placentals. Due to its virtually homoplasy-free nature, the analysis of retroposon presence/absence patterns avoids the pitfalls of other molecular methodologies and provides a rapid, unequivocal means for revealing the evolutionary history of organisms

Acute and short-term administration of a sulfonylurea (gliclazide) increases pulsatile insulin secretion in type 2 diabetes

W cukrzycy typu 2 występują zaburzenia rytmu wydzielania insuliny, który w warunkach prawidłowych ma charakter pulsacji o wysokiej częstotliwości. W leczeniu cukrzycy powszechnie stosuje się pochodne sulfonylomocznika, jednak dotychczas nie ustalono ostatecznie ich wpływu na sposób uwalniania hormonu. Celem przedstawionego badania było określenie efektu jednorazowej dawki i 5-tygodniowego podawania pochodnej sulfonylomocznika (gliklazydu) na dynamikę wydzielania insuliny u chorych na cukrzycę typu 2. Badanie było podwójnie ślepą, kontrolowaną placebo, skrzyżowaną próbą prospektywną, do której włączono 10 chorych na cukrzycę typu 2 (wiek 53 &plusmn; 2 lata, BMI 27,5 &plusmn; 1,1 kg/m2, glikemia na czczo 9,8 &plusmn; 0,8 mmol/l, HbA1c 7,5 &plusmn; 0,3%). Otrzymywali oni 40&#8211;80 mg gliklazydu lub placebo 2 razy dziennie przez 5 tygodni, po 6-tygodniowym okresie przerwy w podawaniu leków. Pomiary insulinemii wykonywano w odstępach minutowych przez 75 minut: 1) w warunkach wyjściowych; 2) 3 godziny po podaniu pierwszej dawki leku (80 mg gliklazydu), przy utrzymaniu glikemii na poziomie wyjściowym; 3) po 5 tygodniach podawania leku i 4) po 5 tygodniach podawania leku, przy utrzymaniu glikemii jak w warunkach wyjściowych (wzrost 5-tygodniowy). W celu oceny ilościowej charakteru pulsacji i regularności wydzielania insuliny stężenia insuliny w przedziałach czasowych poddano analizie metodą spektralną, autokorelacji, dekonwolucji oraz entropii przybliżonej (ApEn, approximate entropy). Podane wartości p dotyczą porównania działania gliklazydu i placebo; wyniki przedstawiono jako średnie &plusmn; SE. Glikemia na czczo obniżyła się po leczeniu gliklazydem (poziom wyjściowy vs. 5 tygodni: gliklazyd 10,0 &plusmn; 0,9 vs. 7,8 &plusmn; 0,6 mmol/l; placebo 10,0 &plusmn; 0,8 vs. 11,0 &plusmn; 0,9 mmol/l, p = 0,001). Stężenia wydzielanej insuliny zwiększyły się (wyjściowe vs. jednorazowe podanie: gliklazyd 43,0 &plusmn; 12,0 vs. 61,0 &plusmn;17,0 pmol/l/puls; placebo 36,1 &plusmn; 8,4 vs. 30,3 &plusmn; 7,4 pmol/l/puls, p = 0,047; wzrost 5-tygodniowy: gliklazyd vs. placebo 49,7 &plusmn; 13,3 vs. 37,1 &plusmn; 9,5 pmol/l/puls, p < 0,05) z podobnym wzrostem amplitudy wydzielania. Podstawowe (niepulsacyjne) wydzielanie insuliny również było podwyższone (wyjściowo vs. jednorazowe podanie: gliklazyd 8,5 &plusmn; 2,2 vs. 16,7 &plusmn; 4,3 pmol/l/puls; placebo 5,9 &plusmn; 0,9 vs. 7,2 &plusmn; 0,9 pmol/l/puls, p = 0,03; wzrost 5-tygodniowy: gliklazyd vs. placebo 12,2 &plusmn; 2,5 vs. 9,4 &plusmn; 2,1 pmol/l/puls, p = 0,016). Częstotliwość i regularność pulsów wydzielania insuliny nie zmieniły się istotnie po zastosowaniu terapii. Zaobserwowano jednak poprawę regularności pulsów po jednorazowym podaniu leku przy badaniu poszczególnych chorych, co oznaczano metodą ApEn, oraz zmniejszenie glikemii na czczo w czasie krótkoterminowego, 5-tygodniowego leczenia gliklazydem (r = 0,74, p = 0,014; r = 0,77, p = 0,009, odpowiednio dla szczegółowej i ogólnej ApEn). Podsumowując, należy stwierdzić, że pochodna sulfonylomocznika &#8212; gliklazyd &#8212; zwiększa wydzielanie insuliny, nasilając zarówno pulsacyjną, jak i podstawową sekrecję insuliny bez wpływu na częstotliwość i regularność pulsów. Dane uzyskane w badaniu sugerują, że może istnieć związek między krótkoterminową poprawą glikemii i poprawą regularności procesu wydzielania insuliny in vivo.The high-frequency oscillatory pattern of insulin release is disturbed in type 2 diabetes. Although sulfonylurea drugs are widely used for the treatment of this disease, their effect on insulin release patterns is not well established. The aim of the present study was to assess the impact of acute treatment and 5 weeks of sulfonylurea (gliclazide) treatment on insulin secretory dynamics in type 2 diabetic patients. To this end, 10 patients with type 2 diabetes (age 53 &plusmn; 2 years, BMI 27.5 &plusmn; 1.1 kg/m2, fasting plasma glucose 9.8 &plusmn; 0.8 mmol/l, HbA1c 7.5 &plusmn; 0.3%) were studied in a double-blind placebo-controlled prospective crossover design. Patients received 40&#8211;80 mg gliclazide/placebo twice daily for 5 weeks with a 6-week washout period intervening. Insulin pulsatility was assessed by 1-min interval blood sampling for 75 min 1) under baseline conditions (baseline), 2) 3 h after the first dose (80 mg) of gliclazide (acute) with the plasma glucose concentration clamped at the baseline value, 3) after 5 weeks of treatment (5 weeks), and 4) after 5 weeks of treatment with the plasma glucose concentration clamped during the sampling at the value of the baseline assessment (5 weeks-elevated). Serum insulin concentration time series were analyzed by deconvolution, approximate entropy (ApEn), and spectral and autocorrelation methods to quantitate pulsatility and regularity. The P values given are gliclazide versus placebo; results are means &plusmn; SE. Fasting plasma glucose was reduced after gliclazide treatment (baseline vs. 5 weeks: gliclazide, 10.0 &plusmn; 0.9 vs. 7.8 &plusmn; 0.6 mmol/l; placebo, 10.0 &plusmn; 0.8 vs. 11.0 &plusmn; 0.9 mmol/l, P = 0.001). Insulin secretory burst mass was increased (baseline vs. acute: gliclazide, 43.0 &plusmn; 12.0 vs. 61.0 &plusmn; 17.0 pmol × l-1 × pulse-1; placebo, 36.1 &plusmn; 8.4 vs. 30.3 &plusmn; 7.4 pmol × l-1 × pulse-1, P = 0.047; 5 weekselevated: gliclazide vs. placebo, 49.7 &plusmn; 13.3 vs. 37.1 &plusmn; 9.5 pmol × l-1 × pulse-1, P < 0.05) with a similar rise in burst amplitude. Basal (i.e., nonoscillatory) insulin secretion also increased (baseline vs. acute: gliclazide, 8.5 &plusmn; 2.2 vs. 16.7 &plusmn; 4.3 pmol × l-1 x pulse&#8211;1; placebo, 5.9 &plusmn; 0.9 vs. 7.2 &plusmn; &plusmn; 0.9 pmol × l-1 × pulse-1, P = 0.03; 5 weeks-elevated: gliclazide vs. placebo, 12.2 &plusmn; 2.5 vs. 9.4 &plusmn; 2.1 pmol × l-1 × pulse-1, P = 0.016). The frequency and regularity of insulin pulses were not modified significantly by the antidiabetic therapy. There was, however, a correlation between individual values for the acute improvement of regularity, as measured by ApEn, and the decrease in fasting plasma glucose during short-term (5-week) gliclazide treatment (r = 0.74, P = 0.014, and r = 0.77, P = 0.009, for fine and coarse ApEn, respectively). In conclusion, the sulfonylurea agent gliclazide augments insulin secretion by concurrently increasing pulse mass and basal insulin secretion without changing secretory burst frequency or regularity. The data suggest a possible relationship between the improvement in short-term glycemic control and the acute improvement of regularity of the in vivo insulin release process

One week's treatment with the long-acting glucagon-like peptide 1 derivate liraglutide (NN2211) markedly improves 24-h glycemia and &#945;- and &#946;-cell function and reduces endogenous glucose release in patients with type 2 diabetes

Glukagonopodobny peptyd 1 (GLP-1, glucagon-like peptide 1) może być bardzo skuteczny w leczeniu cukrzycy typu 2. Autorzy badali wpływ krótkiego (1 tydzień) stosowania pochodnej GLP-1, liraglutydu (NN2211), na 24-godzinny profil glikemii i stężenia krążących wolnych kwasów tłuszczowych, wydzielanie hormonów przez komórki wysp trzustkowych oraz na opróżnianie żołądka podczas posiłków (z użyciem acetaminofenu). Ponadto, oceniali endogenne uwalnianie glukozy na czczo oraz glukoneogenezę (odpowiednio wlew 3-3H-glukozy i wypicie 2H2O), a następnie zbadali funkcję komórek wysp trzustkowych, stosując homeostatyczny model oceny oraz 1. i 2. fazę wydzielania insuliny z użyciem klamry hiperglikemicznej (stężenie glukozy w osoczu wynosiło ok. 16 mmol/l). Na szczycie hiperglikemii wykonano test stymulacji argininą. W badaniu przeprowadzonym jako podwójnie ślepa próba w układzie naprzemiennym z grupą kontrolną placebo wzięło udział 13 chorych na cukrzycę typu 2. Liraglutyd podawano podskórnie raz na dobę (6 &micro;g/kg). Stosowanie leku spowodowało istotne zmniejszenie 24-godzinnego pola pod krzywą dla glukozy (p = 0,01) i glukagonu (p = 0,04), natomiast pole pod krzywą dla krążących wolnych kwasów tłuszczowych nie uległo zmianie. Dobowe wydzielanie insuliny oceniane na podstawie dekonwolucji stężeń C-peptydu w osoczu nie zmieniło się, co wskazuje na jego względny wzrost. Liraglutyd w zastosowanej dawce nie wpłynął na opróżnianie żołądka. Uwalnianie endogennej glukozy na czczo zmniejszyło się (p = 0,04) na skutek zahamowania glikogenolizy (p = 0,01), natomiast nasilenie glukoneogenezy nie uległo zmianie. Pierwsza faza wydzielania insuliny oraz reakcja na argininę w warunkach hiperglikemii wyraźnie się nasiliły (p < 0,001), a współczynnik proinsulina/insulina się zmniejszył (p = 0,001). Wskaźnik podatności (disposition index) (maksymalne stężenie insuliny po dożylnym podaniu bolusa glukozy pomnożone przez insulinowrażliwość obliczoną za pomocą modelu homeostatycznego) niemal podwoił się w czasie leczenia liraglutydem (p < 0,01). W okresie stosowania leku zaobserwowano również zmniejszone wydzielanie glukagonu, zarówno pod wpływem samej hiperglikemii, jak i po podaniu argininy (p < 0,01; p = 0,01). Stosowanie liraglutydu raz na dobę przez 1 tydzień u chorych na cukrzycę typu 2 poprawia 24-godzinną kontrolę glikemii (również po posiłkach i w nocy). Lek ten działa na zasadzie kilku różnych mechanizmów, między innymi poprawia czynność komórek wysp trzustkowych. W badaniu zwrócono uwagę na GLP-1 i jego pochodne jako nowe i obiecujące leki w terapii cukrzycy typu 2.Glucagon-like peptide 1 (GLP-1) is potentially a very attractive agent for treating type 2 diabetes. We explored the effect of short-term (1 week) treatment with a GLP-1 derivative, liraglutide (NN2211), on 24-h dynamics in glycemia and circulating free fatty acids, islet cell hormone profiles, and gastric emptying during meals using acetaminophen. Furthermore, fasting endogenous glucose release and gluconeogenesis (3-3Hglucose infusion and 2H2O ingestion, respectively) were determined, and aspects of pancreatic islet cell function were elucidated on the subsequent day using homeostasis model assessment and first- and second-phase insulin response during a hyperglycemic clamp (plasma glucose ~16 mmol/l), and, finally, on top of hyperglycemia, an arginine stimulation test was performed. For accomplishing this, 13 patients with type 2 diabetes were examined in a double-blind, placebo-controlled crossover design. Liraglutide (6 &#956;g/kg) was administered subcutaneously once daily. Liraglutide significantly reduced the 24-h area under the curve for glucose (P = 0.01) and glucagon (P = 0.04), whereas the area under the curve for circulating free fatty acids was unaltered. Twenty-four-hour insulin secretion rates as assessed by deconvolution of serum C-peptide concentrations were unchanged, indicating a relative increase. Gastric emptying was not influenced at the dose of liraglutide used. Fasting endogenous glucose release was decreased (P = 0.04) as a result of a reduced glycogenolysis (P = 0.01), whereas gluconeogenesis was unaltered. First-phase insulin response and the insulin response to an arginine stimulation test with the presence of hyperglycemia were markedly increased (P < 0.001), whereas the proinsulin/insulin ratio fell (P = 0.001). The disposition index (peak insulin concentration after intravenous bolus of glucose multiplied by insulin sensitivity as assessed by homeostasis model assessment) almost doubled during liraglutide treatment (P < 0.01). Both during hyperglycemia per se and after arginine exposure, the glucagon responses were reduced during liraglutide administration (P < 0.01 and P = 0.01). Thus, 1 week&#8217;s treatment with a single daily dose of the GLP-1 derivative liraglutide, operating through several different mechanisms including an ameliorated pancreatic islet cell function in individuals with type 2 diabetes, improves glycemic control throughout 24 h of daily living, i.e., prandial and nocturnal periods. This study further emphasizes GLP-1 and its derivatives as a promising novel concept for treatment of type 2 diabetes

Orbital Physics in the Perovskite Ti Oxides

In the perovskite Ti oxide RTiO3 (R=rare-earth ions), the Ti t2g orbitals and spins in the 3d^1 state couple each other through the strong electron correlations, resulting in a rich variety of orbital-spin phases. The origin and nature of orbital-spin states of these Mott insulators have been intensively studied. In this article, we review the studies on orbital physics in the perovskite titanates. We focus on the following three topics: (1) the origin and nature of the ferromagnetism as well as the orbital ordering in the compounds with relatively small R ions such as GdTiO3 and YTiO3, (2) the origin of the G-type antiferromagnetism and the orbital state in LaTiO3, and (3) the orbital-spin structures in other AFM(G) compounds with relatively large R ions (R=Ce, Pr, Nd and Sm). On the basis of these discussions, we discuss the whole phase diagram together with mechanisms of the magnetic phase transition. We also show that the Ti t2g degeneracy is inherently lifted in the titanates, which allows the single-band descriptions of the ground-state and low-energy electronic structures as a good starting point. Our analyses indicate that these compounds offer touchstone materials described by the single-band Hubbard model on the cubic lattice. From this insight, we also reanalyze the hole-doped titanates. Experimentally revealed filling-dependent and bandwidth-dependent properties and the critical behavior of the metal-insulator transitions are discussed in the light of theories based on the single-band Hubbard models.Comment: Review article, 26 pages, to appear in New Journal of Physic

Delayed β-cell response and glucose intolerance in young women with Turner syndrome

<p>Abstract</p> <p>Background</p> <p>To investigate glucose homeostasis in detail in Turner syndrome (TS), where impaired glucose tolerance (IGT) and type 2 diabetes are frequent.</p> <p>Methods</p> <p>Cross sectional study of women with Turner syndrome (TS)(n = 13) and age and body mass index matched controls (C) (n = 13), evaluated by glucose tolerance (oral and intravenous glucose tolerance test (OGTT and IVGTT)), insulin sensitivity (hyperinsulinemic, euglycemic clamp), beta-cell function (hyperglycaemic clamp, arginine and GLP-1 stimulation) and insulin pulsatility.</p> <p>Results</p> <p>Fasting glucose and insulin levels were similar. Higher glucose responses was seen in TS during OGTT and IVGTT, persisting after correction for body weight or muscle mass, while insulin responses were similar in TS and C, despite the higher glucose level in TS, leading to an insufficient increase in insulin response during dynamic testing. Insulin sensitivity was comparable in the two groups (TS vs. control: 8.6 ± 1.8 vs. 8.9 ± 1.8 mg/kg*30 min; p = 0.6), and the insulin responses to dynamic β-cell function tests were similar. Insulin secretion patterns examined by deconvolution analysis, approximate entropy, spectral analysis and autocorrelation analysis were similar. In addition we found low IGF-I, higher levels of cortisol and norepinephrine and an increased waist-hip ratio in TS.</p> <p>Conclusions</p> <p>Young normal weight TS women show significant glucose intolerance in spite of normal insulin secretion during hyperglycaemic clamping and normal insulin sensitivity. We recommend regularly testing for diabetes in TS.</p> <p>Trial Registration</p> <p>Registered with <url>http://clinicaltrials.com</url>, ID nr: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00419107">NCT00419107</a></p