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101.
Jun Wen AJ Harris Yash Kalburgi Ning Zhang Yuan Xu Wei Zheng Stefanie M. Ickert-Bond Gabriel Johnson Elizabeth A. Zimmer 《植物分类学报:英文版》2018,56(4):297-308
Vitis L. (the grape genus) is the economically most important fruit crop, as the source of grapes and wine. Phylogenetic relationships within the genus have been highly controversial. Herein, we employ sequence data from whole plastomes to attempt to enhance Vitis phylogenetic resolution. The results support the New World Vitis subgenus Vitis as monophyletic. Within the clade, V. californica is sister to the remaining New World Vitis subgenus Vitis. Furthermore, within subgenus Vitis, a Eurasian clade is robustly supported and is sister to the New World clade. The clade of Vitis vinifera ssp. vinifera and V. vinifera ssp. sylvestris is sister to the core Asian clade of Vitis. Several widespread species in North America are found to be non‐monophyletic in the plastome tree, for example, the broadly defined Vitis cinerea and V. aestivalis each needs to be split into several species. The non‐monophyly of some species may also be due to common occurrences of hybridizations in North American Vitis. The classification of North American Vitis by Munson into nine series is discussed based on the phylogenetic results. Analyses of divergence times and lineage diversification support a rapid radiation of Vitis in North America beginning in the Neogene. 相似文献
102.
MG Mullender NA Blom M De Kleuver JM Fock WMGC Hitters AMC Horemans CJ Kalkman JEH Pruijs RR Timmer PJ Titarsolej NC Van Haasteren Tol-de MJ Van Jager AJ Van Vught BJ Van Royen 《Scoliosis》2008,3(1):1-14
Background
Children with neuromuscular disorders with a progressive muscle weakness such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy frequently develop a progressive scoliosis. A severe scoliosis compromises respiratory function and makes sitting more difficult. Spinal surgery is considered the primary treatment option for correcting severe scoliosis in neuromuscular disorders. Surgery in this population requires a multidisciplinary approach, careful planning, dedicated surgical procedures, and specialized after care.Methods
The guideline is based on scientific evidence and expert opinions. A multidisciplinary working group representing experts from all relevant specialties performed the research. A literature search was conducted to collect scientific evidence in answer to specific questions posed by the working group. Literature was classified according to the level of evidence.Results
For most aspects of the treatment scientific evidence is scarce and only low level cohort studies were found. Nevertheless, a high degree of consensus was reached about the management of patients with scoliosis in neuromuscular disorders. This was translated into a set of recommendations, which are now officially accepted as a general guideline in the Netherlands.Conclusion
In order to optimize the treatment for scoliosis in neuromuscular disorders a Dutch guideline has been composed. This evidence-based, multidisciplinary guideline addresses conservative treatment, the preoperative, perioperative, and postoperative care of scoliosis in neuromuscular disorders. 相似文献103.
Background
Obligate asexual reproduction is rare in the animal kingdom. Generally, asexuals are considered evolutionary dead ends that are unable to radiate. The phytophagous mite genus Bryobia contains a large number of asexual species. In this study, we investigate the origin and evolution of asexuality using samples from 111 populations in Europe, South Africa and the United States, belonging to eleven Bryobia species. We also examine intraspecific clonal diversity for one species, B. kissophila, by genotyping individuals from 61 different populations. Knowledge on the origin of asexuality and on clonal diversity can contribute to our understanding of the paradox of sex. 相似文献104.
Banfor PN Preusser LC Campbell TJ Marsh KC Polakowski JS Reinhart GA Cox BF Fryer RM 《American journal of physiology. Heart and circulatory physiology》2008,294(1):H238-H248
Levosimendan enhances cardiac contractility via Ca(2+) sensitization and induces vasodilation through the activation of ATP-dependent K(+) and large-conductance Ca(2+)-dependent K(+) channels. However, the hemodynamic effects of levosimendan, as well as its metabolites, OR-1896 and OR-1855, relative to plasma concentrations achieved, are not well defined. Thus levosimendan, OR-1896, OR-1855, or vehicle was infused at 0.01, 0.03, 0.1, and 0.3 mumol.kg(-1).30 min(-1), targeting therapeutic to supratherapeutic concentrations of total levosimendan (62.6 ng/ml). Results were compared with those of the beta(1)-agonist dobutamine and the phosphodiesterase 3 inhibitor milrinone. Peak concentrations of levosimendan, OR-1896, and OR-1855 were 455 +/- 21, 126 +/- 6, and 136 +/- 6 ng/ml, respectively. Levosimendan and OR-1896 produced dose-dependent reductions in mean arterial pressure (-31 +/- 2 and -42 +/- 3 mmHg, respectively) and systemic resistance without affecting pulse pressure, effects paralleled by increases in heart rate; OR-1855 produced no effect at any dose tested. Dobutamine, but not milrinone, increased mean arterial pressure and pulse pressure (17 +/- 2 and 23 +/- 2 mmHg, respectively). Regarding potency to elicit reductions in time to peak pressure and time to systolic pressure recovery: OR-1896 > levosimendan > milrinone > dobutamine. Levosimendan and OR-1896 elicited dose-dependent increases in change in pressure over time (118 +/- 10 and 133 +/- 13%, respectively), concomitant with reductions in left ventricular end-diastolic pressure and ejection time. However, neither levosimendan nor OR-1896 produced increases in myocardial oxygen consumption at inotropic and vasodilatory concentrations, whereas dobutamine increased myocardial oxygen consumption (79% above baseline). Effects of the levosimendan and OR-1896 were limited to the systemic circulation; neither compound produced changes in pulmonary pressure, whereas dobutamine produced profound increases (74 +/- 13%). Thus levosimendan and OR-1896 are hemodynamically active in the anesthetized dog at concentrations observed clinically and elicit cardiovascular effects consistent with activation of both K(+) channels and Ca(2+) sensitization, whereas OR-1855 is inactive on endpoints measured in this study. 相似文献
105.
Penning TD Zhu GD Gandhi VB Gong J Thomas S Lubisch W Grandel R Wernet W Park CH Fry EH Liu X Shi Y Klinghofer V Johnson EF Donawho CK Frost DJ Bontcheva-Diaz V Bouska JJ Olson AM Marsh KC Luo Y Rosenberg SH Giranda VL 《Bioorganic & medicinal chemistry》2008,16(14):6965-6975
We have developed a series of cyclic amine-containing benzimidazole carboxamide poly(ADP-ribose)polymerase (PARP) inhibitors, with good PARP-1 enzyme potency, as well as cellular potency. These efforts led to the identification of a lead preclinical candidate, 10b, 2-(1-propylpiperidin-4-yl)-1H-benzimidazole-4-carboxamide (A-620223). 10b displayed very good potency against both the PARP-1 enzyme with a K(i) of 8nM and in a whole cell assay with an EC(50) of 3nM. 10b is aqueous soluble, orally bioavailable across multiple species, and demonstrated good in vivo efficacy in a B16F10 subcutaneous murine melanoma model in combination with temozolomide (TMZ) and in an MX-1 breast xenograph model in combination with cisplatin. 相似文献
106.
Bas Brinkhof Helena TA van Tol Marian JA Groot Koerkamp Frank M Riemers Sascha G IJzer Kaveh Mashayekhi Henk P Haagsman Bernard AJ Roelen 《BMC genomics》2015,16(1)
Background
Genes and signalling pathways involved in pluripotency have been studied extensively in mouse and human pre-implantation embryos and embryonic stem (ES) cells. The unsuccessful attempts to generate ES cell lines from other species including cattle suggests that other genes and pathways are involved in maintaining pluripotency in these species. To investigate which genes are involved in bovine pluripotency, expression profiles were generated from morula, blastocyst, trophectoderm and inner cell mass (ICM) samples using microarray analysis. As MAPK inhibition can increase the NANOG/GATA6 ratio in the inner cell mass, additionally blastocysts were cultured in the presence of a MAPK inhibitor and changes in gene expression in the inner cell mass were analysed.Results
Between morula and blastocyst 3,774 genes were differentially expressed and the largest differences were found in blastocyst up-regulated genes. Gene ontology (GO) analysis shows lipid metabolic process as the term most enriched with genes expressed at higher levels in blastocysts. Genes with higher expression levels in morulae were enriched in the RNA processing GO term. Of the 497 differentially expressed genes comparing ICM and TE, the expression of NANOG, SOX2 and POU5F1 was increased in the ICM confirming their evolutionary preserved role in pluripotency. Several genes implicated to be involved in differentiation or fate determination were also expressed at higher levels in the ICM. Genes expressed at higher levels in the ICM were enriched in the RNA splicing and regulation of gene expression GO term. Although NANOG expression was elevated upon MAPK inhibition, SOX2 and POU5F1 expression showed little increase. Expression of other genes in the MAPK pathway including DUSP4 and SPRY4, or influenced by MAPK inhibition such as IFNT, was down-regulated.Conclusion
The data obtained from the microarray studies provide further insight in gene expression during bovine embryonic development. They show an expression profile in pluripotent cells that indicates a pluripotent, epiblast-like state. The inability to culture ICM cells as stem cells in the presence of an inhibitor of MAPK activity together with the reported data indicates that MAPK inhibition alone is not sufficient to maintain a pluripotent character in bovine cells.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1448-x) contains supplementary material, which is available to authorized users. 相似文献107.
Judd AS Souers AJ Wodka D Zhao G Mulhern MM Iyengar RR Gao J Lynch JK Freeman JC Falls HD Brodjian S Dayton BD Reilly RM Gintant G Limberis JT Mikhail A Leitza ST Houseman KA Diaz G Bush EN Shapiro R Knourek-Segel V Hernandez LE Marsh KC Sham HL Collins CA Kym PR 《Bioorganic & medicinal chemistry letters》2007,17(8):2365-2371
A series of potent 2-carboxychromone-based melanin-concentrating hormone receptor 1 (MCHr1) antagonists were synthesized and evaluated for hERG (human Ether-a-go-go Related Gene) channel affinity and functional blockade. Basic dialkylamine-terminated analogs were found to weakly bind the hERG channel and provided marked improvement in a functional patch-clamp assay versus previously reported antagonists of the series. 相似文献
108.
Souers AJ Iyengar RR Judd AS Beno DW Gao J Zhao G Brune ME Napier JJ Mulhern MM Lynch JK Freeman JC Wodka D Chen CJ Falls HD Brodjian S Dayton BD Diaz GJ Bush EN Shapiro R Droz BA Knourek-Segel V Hernandez LE Marsh KC Reilly RM Sham HL Collins CA Kym PR 《Bioorganic & medicinal chemistry letters》2007,17(4):884-889
The incorporation of constrained tertiary amines into an existing class of N-benzyl-4-aminopiperidinyl chromone-based MCHr1 antagonists led to the identification of a series of chiral racemic compounds that displayed good to excellent functional potency, binding affinity, and selectivity over the hERG channel. Further separation of two distinct chiral racemic compounds into their corresponding pairs of enantiomers revealed a considerable selectivity for MCHr1 for one configuration, in addition to a striking difference in oral exposure between one pair of enantiomers in diet-induced obese mice. Oral administration of the most potent compound in this class in the same animal model led to significant reduction of fat mass in a semi-chronic model for weight loss. 相似文献
109.
Gomtsyan A Bayburt EK Keddy R Turner SC Jinkerson TK Didomenico S Perner RJ Koenig JR Drizin I McDonald HA Surowy CS Honore P Mikusa J Marsh KC Wetter JM Faltynek CR Lee CH 《Bioorganic & medicinal chemistry letters》2007,17(14):3894-3899
SAR studies for N-aryl-N'-benzyl urea class of TRPV1 antagonists have been extended to cover alpha-benzyl alkylation. Alkylated compounds showed weaker in vitro potencies in blocking capsaicin activation of TRPV1 receptor, but possessed improved pharmacokinetic properties. Further structural manipulations that included replacement of isoquinoline core with indazole and isolation of single enantiomer led to TRPV1 antagonists like (R)-16a with superior pharmacokinetic properties and greater potency in animal model of inflammatory pain. 相似文献
110.
Blaney Davidson EN Vitters EL van Lent PL van de Loo FA van den Berg WB van der Kraan PM 《Arthritis research & therapy》2007,9(5):R102
Bone morphogenetic protein-2 (BMP-2) has been proposed as a tool for cartilage repair and as a stimulant of chondrogenesis.
In healthy cartilage, BMP-2 is hardly present, whereas it is highly expressed during osteoarthritis. To assess its function
in cartilage, BMP-2 was overexpressed in healthy murine knee joints and the effects on proteoglycan (PG) synthesis and degradation
were evaluated. Moreover, the contribution of BMP in repairing damage induced by interleukin-1 (IL-1) was investigated. Ad-BMP-2
was injected intra-articularly into murine knee joints, which were isolated 3, 7, and 21 days after injection for histology,
immunohistochemistry, and autoradiography. In addition, patellar and tibial cartilage was isolated for RNA isolation or measurement
of PG synthesis by means of 35SO4
2- incorporation. To investigate the role for BMP-2 in cartilage repair, cartilage damage was induced by intra-articular injection
of IL-1. After 2 days, Ad-BMP-2, Ad-BMP-2 + Ad-gremlin, Ad-gremlin, or a control virus was injected. Whole knee joints were
isolated for histology at day 4 or patellae were isolated to measure 35SO4
2- incorporation. BMP-2 stimulated PG synthesis in patellar cartilage on all days and in tibial cartilage on day 21. Aggrecan
mRNA expression had increased on all days in patellar cartilage, with the highest increase on day 7. Collagen type II expression
showed a similar expression pattern. In tibial cartilage, collagen type II and aggrecan mRNA expression had increased on days
7 and 21. BMP-2 overexpression also induced increased aggrecan degradation in cartilage. VDIPEN staining (indicating matrix
metalloproteinase activity) was elevated on day 3 in tibial cartilage and on days 3 and 7 in patellar cartilage, but no longer
was by day 21. Increased NITEGE staining (indicating aggrecanase activity) was found on days 7 and 21. In IL-1-damaged patellar
cartilage, BMP-2 boosted PG synthesis. Blocking of BMP activity resulted in a decreased PG synthesis compared with IL-1 alone.
This decreased PG synthesis was associated with PG depletion in the cartilage. These data show that BMP-2 boosts matrix turnover
in intact and IL-damaged cartilage. Moreover, BMP contributes to the intrinsic repair capacity of damaged cartilage. Increased
matrix turnover might be functional in replacing matrix molecules in the repair of a damaged cartilage matrix. 相似文献