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931.
Background
Hundreds of thousands of human embryos are cultured yearly at in vitro fertilization (IVF) centers worldwide, yet the vast majority fail to develop in culture or following transfer to the uterus. However, human embryo phenotypes have not been formally defined, and current criteria for embryo transfer largely focus on characteristics of individual embryos. We hypothesized that embryo cohort-specific variables describing sibling embryos as a group may predict developmental competence as measured by IVF cycle outcomes and serve to define human embryo phenotypes.Methodology/Principal Findings
We retrieved data for all 1117 IVF cycles performed in 2005 at Stanford University Medical Center, and further analyzed clinical data from the 665 fresh IVF, non-donor cycles and their associated 4144 embryos. Thirty variables representing patient characteristics, clinical diagnoses, treatment protocol, and embryo parameters were analyzed in an unbiased manner by regression tree models, based on dichotomous pregnancy outcomes defined by positive serum ß-human chorionic gonadotropin (ß-hCG). IVF cycle outcomes were most accurately predicted at ∼70% by four non-redundant, embryo cohort-specific variables that, remarkably, were more informative than any measures of individual, transferred embryos: Total number of embryos, number of 8-cell embryos, rate (percentage) of cleavage arrest in the cohort and day 3 follicle stimulating hormone (FSH) level. While three of these variables captured the effects of other significant variables, only the rate of cleavage arrest was independent of any known variables.Conclusions/Significance
Our findings support defining human embryo phenotypes by non-redundant, prognostic variables that are specific to sibling embryos in a cohort. 相似文献932.
933.
Illig CR Chen J Wall MJ Wilson KJ Ballentine SK Rudolph MJ DesJarlais RL Chen Y Schubert C Petrounia I Crysler CS Molloy CJ Chaikin MA Manthey CL Player MR Tomczuk BE Meegalla SK 《Bioorganic & medicinal chemistry letters》2008,18(5):1642-1648
The optimization of the arylamide lead 2 resulted in identification of a highly potent series of 2,4-disubstituted arylamides. Compound 8 (FMS kinase IC(50)=0.0008 microM) served as a proof-of-concept candidate in a collagen-induced model of arthritis in mice. 相似文献
934.
Winters MP Robinson DJ Khine HH Pullen SS Woska JR Raymond EL Sellati R Cywin CL Snow RJ Kashem MA Wolak JP King J Kaplita PV Liu LH Farrell TM DesJarlais R Roth GP Takahashi H Moriarty KJ 《Bioorganic & medicinal chemistry letters》2008,18(20):5541-5544
A series of novel 5-aminomethyl-1H-benzimidazole based inhibitors of Itk were prepared. Structure-activity relationships, selectivity and cell activity are reported for this series. Compound 2, a potent and selective antagonist of Itk, inhibited anti-CD3 antibody induced IL-2 production in vivo in mice. 相似文献
935.
Drosophila odorant receptors are novel seven transmembrane domain proteins that can signal independently of heterotrimeric G proteins 总被引:3,自引:0,他引:3
Smart R Kiely A Beale M Vargas E Carraher C Kralicek AV Christie DL Chen C Newcomb RD Warr CG 《Insect biochemistry and molecular biology》2008,38(8):770-780
Olfaction in Drosophila is mediated by a large family of membrane-bound odorant receptor proteins (Ors). In heterologous cells, we investigated whether the structural features and signalling mechanisms of ligand-binding Drosophila Ors are consistent with them being G protein-coupled receptors (GPCRs). The detailed membrane topology of Or22a was determined by inserting epitope tags into the termini and predicted loop regions. Immunocytochemistry experiments in Drosophila S2 cells imply that Or22a has seven transmembrane domains but that its membrane topology is opposite to that of GPCRs, with a cytoplasmic N-terminus and extracellular C-terminus. To investigate Or signalling mechanisms, we expressed Or43b in Sf9 and HEK293 cells, and show that inhibitors of heterotrimeric G proteins (GDP-beta-S), adenylate cyclase (SQ22536), guanylyl cyclase (ODQ), cyclic nucleotide phosphodiesterases (IBMX) and phospholipase C (U73122) have negligible impact on Or43b responses. Whole cell patching of Or43b/Or83b-transfected HEK293 cells revealed the opening of plasma membrane cation channels on addition of ligand. The response was blocked by lanthanum and by 2-APB, but not by Ruthenium red or SKF96365. Based on these data, we conclude that Drosophila Ors comprise a novel family of seven transmembrane receptors that in HEK293 cells signal by opening cation channels, through a mechanism that is largely independent of G proteins. 相似文献
936.
James Ashe Abdel El Manira Bambos Kyriacou Stephen F Goodwin Andrew Lumsden Susan Chapman Stefan Jungbluth Esther Bell Ana Coutinho Moheb Costandi Niels Adams Renee Dutton Mark Mayford Barbara Knowlton Michael Husser Venkatesh N Murthy John N Wood John A Assad Morgan Sheng Marie T Filbin Jin Qiu Eugene P Brandon Fred H Gage 《Current opinion in neurobiology》1999,9(6):645
A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in neurobiology. 相似文献
937.
Well-characterized traits important to Candida albicans virulence, such as hyphal formation or secreted proteinase activity, play no known role in Candida glabrata virulence. Likewise, some C. glabrata characteristics, such as chromatin-based regulation of the large telomeric family of lectins encoded by the EPA (epithelial adhesin) genes, have no precise parallels in C. albicans. However, similarities between the two species, for example in population structure, in the large numbers of (putative) adhesins that they encode, and in phenotypic plasticity conferred by phenotypic switching, suggest that they share general strategies in adaptation to an opportunistic lifestyle. 相似文献
938.
Noramly S Zimmerman L Cox A Aloise R Fisher M Grainger RM 《Mechanisms of development》2005,122(3):273-287
In the rapidly developing, diploid amphibian Xenopus tropicalis, genetics can be married to the already powerful tools of the amphibian system to overcome a disability that has hampered Xenopus laevis as a model organism: the difficulties inherent in conducting genetic analyses in a tetraploid organism with a longer generation time. We describe here a gynogenetic screen to uncover naturally occurring recessive mutations in wild X. tropicalis populations, a procedure that is both faster and easier than conventional genetic screens traditionally employed in model organisms to dissect early developmental pathways. During the first round of our screen, gynogenetic diploids from over 160 females comprising four different wild-caught populations were examined. Forty-two potential mutant phenotypes were isolated during this round of gynogenesis. From this group, we describe 10 lines that have genetically heritable recessive mutations. A wide range of developmental defects were obtained in this screen, encompassing effects limited to individual organs as well phenotypes characterized by more global changes in tadpole body morphology. The frequency of recessive mutations detected in our screen appears lower than that seen in other vertebrate genetic screens, but given constraints on the screening procedure used here, is likely to be consistent with rates seen in other animals, and clearly illustrates how wild-caught animals can be a productive source of developmental mutations for experimental study. The development of genetic strategies for the Xenopus system, together with new genomic resources, existing technologies for transgenesis, and other means for manipulating gene expression, as well as the power of performing embryonic manipulations, will provide an impressive set of tools for resolving complex cell and developmental phenomena in the future. 相似文献
939.
Rauch T Hundley HA Pfund C Wegrzyn RD Walter W Kramer G Kim SY Craig EA Deuerling E 《Molecular microbiology》2005,57(2):357-365
Ribosome-tethered chaperones that interact with nascent polypeptide chains have been identified in both prokaryotic and eukaryotic systems. However, these ribosome-associated chaperones share no sequence similarity: bacterial trigger factors (TF) form an independent protein family while the yeast machinery is Hsp70-based. The absence of any component of the yeast machinery results in slow growth at low temperatures and sensitivity to aminoglycoside protein synthesis inhibitors. After establishing that yeast ribosomal protein Rpl25 is able to recruit TF to ribosomes when expressed in place of its Escherichia coli homologue L23, the ribosomal TF tether, we tested whether such divergent ribosome-associated chaperones are functionally interchangeable. E. coli TF was expressed in yeast cells that lacked the endogenous ribosome-bound machinery. TF associated with yeast ribosomes, cross-linked to yeast nascent polypeptides and partially complemented the aminoglycoside sensitivity, demonstrating that ribosome-associated chaperones from divergent organisms share common functions, despite their lack of sequence similarity. 相似文献
940.
The fitness advantage provided by caulinary domatia to myrmecophytes has never been directly demonstrated because most myrmecophytic
species do not present any individual variation in the presence of domatia and the removal of domatia from entire plants is
a destructive process. The semi-myrmecophytic tree, Humboldtia brunonis (Fabaceae: Caesalpinioideae), is an ideal species to investigate the selective advantage conferred by domatia because within
the same population, some plants are devoid of domatia while others bear them. Several ant species patrol the plant for extra-floral
nectar. Fruit production was found to be enhanced in domatia-bearing trees compared to trees devoid of domatia independent
of the ant associate. However, this domatium effect was most conspicuous for trees associated with the populous and nomadic
ant, Technomyrmex albipes. This species is a frequent associate of H. brunonis, inhabiting its domatia or building carton nests on it. Ant exclusion experiments revealed that T. albipes was the only ant to provide efficient anti-herbivore protection to the leaves of its host tree. Measures of ant activity
as well as experiments using caterpillars revealed that the higher efficiency of T. albipes was due to its greater patrolling density and consequent shorter lag time in attacking the larvae. T. albipes also provided efficient anti-herbivore protection to flowers since fruit initiation was greater on ant-patrolled inflorescences
than on those from which ants were excluded. We therefore demonstrated that caulinary domatia provide a selective advantage
to their host-plant and that biotic defence is potentially the main fitness benefit mediated by domatia. However, it is not
the sole advantage. The general positive effect of domatia on fruit set in this ant–plant could reflect other benefits conferred
by domatia-inhabitants, which are not restricted to ants in this myrmecophyte, but comprise a large diversity of other invertebrates.
Our results indicate that mutualisms enhance the evolution of myrmecophytism. 相似文献