排序方式: 共有22条查询结果,搜索用时 31 毫秒
1.
Florian Villegas Daphné Lehalle Daniela Mayer Melanie Rittirsch Michael B. Stadler Marietta Zinner Daniel Olivieri Pierre Vabres Laurence Duplomb-Jego Eveline S.J.M. De Bont Yannis Duffourd Floor Duijkers Magali Avila David Geneviève Nada Houcinat Thibaud Jouan Paul Kuentz Klaske D. Lichtenbelt Joerg Betschinger 《Cell Stem Cell》2019,24(2):257-270.e8
2.
van den Bos R van der Horst KJ Baars AM Spruijt BM 《Alternatives to laboratory animals : ATLA》2002,30(3):299-304
A study in which the rat social discrimination test was refined is described. This test measures social memory by using, in general, juvenile rats as stimulus animals. Rats are offered a first juvenile to investigate (learning trial), and after a specified interval, the rats are offered the same rat and a second juvenile rat to investigate again (retrieval trial). When the rats sniff the second juvenile in the retrieval trial more than the first, social memory for the second juvenile is said to be present. This test is mainly based on scents from the juvenile. Attempts were made to refine the test to reduce the number of animals used, to enhance the scope of the test, and to improve its validity. Firstly, the stimulus animals were replaced by the scent of juveniles, in the form of cups filled with sawdust taken from cages of juvenile rats. Similar results to those in the original test were obtained when using these scents. Furthermore, male and female scents were tested, and showed the same results as for the juvenile scents. Secondly, rats were also given two cups (one scent-filled and one filled with plain sawdust) in the learning trial, to determine which allowed a more-precise delineation of motivational, discriminatory and memory components. Overall, it is possible to replace stimulus animals by scent-filled cups in the social discrimination test, to enhance the scope of the test, and to draw more-valid conclusions with respect to social memory. 相似文献
3.
Summary Sporulation preceded by meiosis was induced in young, diploid plants of Ulva mutabilis, mutant slender (Föyn). The induction was brought about either by replacement of the old culture medium (sea water plus soil extract) with new, or by the addition of a mixture of seven vitamins to old medium. The new chemical environment seems to induce a shift from presumptive mitosis to presumptive meiosis.Supported by a Danish State scholarship '63/'64 from the Danish Ministry of Education. 相似文献
4.
Sipkema D Schippers K Maalcke WJ Yang Y Salim S Blanch HW 《Applied and environmental microbiology》2011,77(6):2130-2140
Three methods were examined to cultivate bacteria associated with the marine sponge Haliclona (gellius) sp.: agar plate cultures, liquid cultures, and floating filter cultures. A variety of oligotrophic media were employed, including media with aqueous and organic sponge extracts, bacterial signal molecules, and siderophores. More than 3,900 isolates were analyzed, and 205 operational taxonomic units (OTUs) were identified. Media containing low concentrations of mucin or a mixture of peptone and starch were most successful for the isolation of diversity, while the commonly used marine broth did not result in a high diversity among isolates. The addition of antibiotics generally led to a reduced diversity on plates but yielded different bacteria than other media. In addition, diversity patterns of isolates from agar plates, liquid cultures, and floating filters were significantly different. Almost 89% of all isolates were Alphaproteobacteria; however, members of phyla that are less commonly encountered in cultivation studies, such as Planctomycetes, Verrucomicrobia, and Deltaproteobacteria, were isolated as well. The sponge-associated bacteria were categorized into three different groups. The first group represented OTUs that were also obtained in a clone library from previously analyzed sponge tissue (group 1). Furthermore, we distinguished OTUs that were obtained from sponge tissue (in a previous study) but not from sponge isolates (group 2), and there were also OTUs that were not obtained from sponge tissue but were obtained from sponge isolates (group 3). The 17 OTUs categorized into group 1 represented 10 to 14% of all bacterial OTUs that were present in a large clone library previously generated from Haliclona (gellius) sp. sponge tissue, which is higher than previously reported cultivability scores for sponge-associated bacteria. Six of these 17 OTUs were not obtained from agar plates, which underlines that the use of multiple cultivation methods is worthwhile to increase the diversity of the cultivable microorganisms from sponges. 相似文献
5.
Alberta A.H.J. Thiadens Anneke I. den Hollander Susanne Roosing Renate C. Zekveld-Vroon Elfride De Baere Mary J. van Schooneveld Janneke J.C. van Lith-Verhoeven Norka van Moll-Ramirez L. Ingeborgh van den Born Frans P.M. Cremers Caroline C.W. Klaver 《American journal of human genetics》2009,85(2):240-247
Cone photoreceptor disorders form a clinical spectrum of diseases that include progressive cone dystrophy (CD) and complete and incomplete achromatopsia (ACHM). The underlying disease mechanisms of autosomal recessive (ar)CD are largely unknown. Our aim was to identify causative genes for these disorders by genome-wide homozygosity mapping. We investigated 75 ACHM, 97 arCD, and 20 early-onset arCD probands and excluded the involvement of known genes for ACHM and arCD. Subsequently, we performed high-resolution SNP analysis and identified large homozygous regions spanning the PDE6C gene in one sibling pair with early-onset arCD and one sibling pair with incomplete ACHM. The PDE6C gene encodes the cone α subunit of cyclic guanosine monophosphate (cGMP) phosphodiesterase, which converts cGMP to 5′-GMP, and thereby plays an essential role in cone phototransduction. Sequence analysis of the coding region of PDE6C revealed homozygous missense mutations (p.R29W, p.Y323N) in both sibling pairs. Sequence analysis of 104 probands with arCD and 10 probands with ACHM revealed compound heterozygous PDE6C mutations in three complete ACHM patients from two families. One patient had a frameshift mutation and a splice defect; the other two had a splice defect and a missense variant (p.M455V). Cross-sectional retinal imaging via optical coherence tomography revealed a more pronounced absence of cone photoreceptors in patients with ACHM compared to patients with early-onset arCD. Our findings identify PDE6C as a gene for cone photoreceptor disorders and show that arCD and ACHM constitute genetically and clinically overlapping phenotypes. 相似文献
6.
Maja Hempel Kirsten Cremer Charlotte?W. Ockeloen Klaske?D. Lichtenbelt Johanna?C. Herkert Jonas Denecke Tobias?B. Haack Alexander?M. Zink Jessica Becker Eva Wohlleber Jessika Johannsen Bader Alhaddad Rolph Pfundt Sigrid Fuchs Dagmar Wieczorek Tim?M. Strom Koen?L.I. van?Gassen Tjitske Kleefstra Christian Kubisch Hartmut Engels Davor Lessel 《American journal of human genetics》2015,97(3):493-500
CHAMP1 encodes a protein with a function in kinetochore-microtubule attachment and in the regulation of chromosome segregation, both of which are known to be important for neurodevelopment. By trio whole-exome sequencing, we have identified de novo deleterious mutations in CHAMP1 in five unrelated individuals affected by intellectual disability with severe speech impairment, motor developmental delay, muscular hypotonia, and similar dysmorphic features including short philtrum and a tented upper and everted lover lip. In addition to two frameshift and one nonsense mutations, we found an identical nonsense mutation, c.1192C>T (p.Arg398∗), in two affected individuals. All mutations, if resulting in a stable protein, are predicted to lead to the loss of the functionally important zinc-finger domains in the C terminus of the protein, which regulate CHAMP1 localization to chromosomes and the mitotic spindle, thereby providing a mechanistic understanding for their pathogenicity. We thus establish deleterious de novo mutations in CHAMP1 as a cause of intellectual disability. 相似文献
7.
Jorge Garcia-Martinez Bjorn Bakker Klaske M Schukken Judith E Simon Floris Foijer 《World journal of stem cells》2016,8(6):216-222
Stem cells hold enormous promise for regenerative medicine as well as for engineering of model systems to study diseases and develop new drugs. The discovery of protocols that allow for generating induced pluripotent stem cells(IPSCs) from somatic cells has brought this promise steps closer to reality. However,as somatic cells might have accumulated various chromosomal abnormalities,including aneuploidies throughout their lives,the resulting IPSCs might no longer carry the perfect blueprint for the tissue to be generated,or worse,become at risk of adopting a malignant fate. In this review,we discuss the contribution of aneuploidy to healthy tissues and how aneuploidy can lead to disease. Furthermore,we review the differences between how somatic cells and stem cells respond to aneuploidy. 相似文献
8.
Prognostic significance of tumor-infiltrating T-lymphocytes in primary and metastatic lesions of advanced stage ovarian cancer 总被引:1,自引:0,他引:1
Leffers N Gooden MJ de Jong RA Hoogeboom BN ten Hoor KA Hollema H Boezen HM van der Zee AG Daemen T Nijman HW 《Cancer immunology, immunotherapy : CII》2009,58(3):449-459
Purpose Ovarian cancer patients with intra-tumoral CD3+ T-lymphocytes in primary tumor tissue have a better prognosis. This study aims to analyze the presence and relative influence
of three important T-lymphocyte subsets, tumor-infiltrating CD8+ cytotoxic T-lymphocytes (CTL), CD45R0+ memory T-lymphocytes, and FoxP3+ regulatory T-lymphocytes (Treg), in primary tumor tissue and omental metastases of patients with ovarian cancer.
Experimental design The number of CD8+, CD45R0+, and FoxP3+ T-lymphocytes was determined by immunohistochemistry on a tissue micro array containing ovarian tumor tissue and/or omental
metastases obtained at primary debulking surgery from 306 FIGO stage I–IV ovarian cancer patients. Immunohistochemistry data
were correlated to clinicopathological parameters and survival data.
Results High number of CD8+ CTL and a high CD8+/FoxP3+ ratio in ovarian-derived tumor tissue were associated with increased disease-specific survival and proved to be independent
prognostic factors in multivariate analyses. In advanced stage patients, the presence of CD8+ CTL, CD45R0+ memory T-lymphocytes, FoxP3+ Treg or a high CD8+/FoxP3+ ratio in ovarian-derived tumor tissue was associated with an increased disease specific survival in univariate analysis,
as was the presence of CD45R0+ memory T-lymphocytes and FoxP3+ Treg in omental metastases. Furthermore, in advanced stage patients CD8+ cytotoxic and FoxP3+ regulatory T-lymphocytes infiltrating ovarian-derived tumor tissue were independent predictors of increased prognosis.
Conclusions T-lymphocytes infiltrating primary and metastatic ovarian cancer sites are associated with improved prognosis. These associations
are especially distinct in advanced stage patients, underlining the potential for immunotherapy as a broadly applicable therapeutic
strategy.
Ninke Leffers and Marloes J. M. Gooden contributed equally. 相似文献
9.
Stephan J. A. C. Peters Tamara Vanhaecke Peggy Papeleu Vera Rogiers Henk P. Haagsman Klaske van Norren 《Cell and tissue research》2010,340(3):451-457
Three different primary rat hepatocyte culture methods were compared for their ability to allow the secretion of fibrinogen
and albumin under basal and IL-6-stimulated conditions. These culture methods comprised the co-culture of hepatocytes with
rat liver epithelial cells (CC-RLEC), a collagen type I sandwich culture (SW) and a conventional primary hepatocyte monolayer
culture (ML). Basal albumin secretion was most stable over time in SW. Fibrinogen secretion was induced by IL-6 in all cell
culture models. Compared with ML, CC-RLEC showed an almost three-fold higher fibrinogen secretion under both control and IL-6-stimulated
conditions. Induction of fibrinogen release by IL-6 was lowest in SW. Albumin secretion was decreased after IL-6 stimulation
in both ML and CC-RLEC. Thus, cells growing under the various primary hepatocyte cell culture techniques react differently
to IL-6 stimulation with regard to acute-phase protein secretion. CC-RLEC is the preferred method for studying cytokine-mediated
induction of acute-phase proteins, because of the pronounced stimulation of fibrinogen secretion upon IL-6 exposure under
these conditions. 相似文献
10.
Talkowski ME Mullegama SV Rosenfeld JA van Bon BW Shen Y Repnikova EA Gastier-Foster J Thrush DL Kathiresan S Ruderfer DM Chiang C Hanscom C Ernst C Lindgren AM Morton CC An Y Astbury C Brueton LA Lichtenbelt KD Ades LC Fichera M Romano C Innis JW Williams CA Bartholomew D Van Allen MI Parikh A Zhang L Wu BL Pyatt RE Schwartz S Shaffer LG de Vries BB Gusella JF Elsea SH 《American journal of human genetics》2011,(4):551-563
Persons with neurodevelopmental disorders or autism spectrum disorder (ASD) often harbor chromosomal microdeletions, yet the individual genetic contributors within these regions have not been systematically evaluated. We established a consortium of clinical diagnostic and research laboratories to accumulate a large cohort with genetic alterations of chromosomal region 2q23.1 and acquired 65 subjects with microdeletion or translocation. We sequenced translocation breakpoints; aligned microdeletions to determine the critical region; assessed effects on mRNA expression; and examined medical records, photos, and clinical evaluations. We identified a single gene, methyl-CpG-binding domain 5 (MBD5), as the only locus that defined the critical region. Partial or complete deletion of MBD5 was associated with haploinsufficiency of mRNA expression, intellectual disability, epilepsy, and autistic features. Fourteen alterations, including partial deletions of noncoding regions not typically captured or considered pathogenic by current diagnostic screening, disrupted MBD5 alone. Expression profiles and clinical characteristics were largely indistinguishable between MBD5-specific alteration and deletion of the entire 2q23.1 interval. No copy-number alterations of MBD5 were observed in 7878 controls, suggesting MBD5 alterations are highly penetrant. We surveyed MBD5 coding variations among 747 ASD subjects compared to 2043 non-ASD subjects analyzed by whole-exome sequencing and detected an association with a highly conserved methyl-CpG-binding domain missense variant, p.79Gly>Glu (c.236G>A) (p = 0.012). These results suggest that genetic alterations of MBD5 cause features of 2q23.1 microdeletion syndrome and that this epigenetic regulator significantly contributes to ASD risk, warranting further consideration in research and clinical diagnostic screening and highlighting the importance of chromatin remodeling in the etiology of these complex disorders. 相似文献