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51.
Peter J Brasted Timothy J Bussey Elisabeth A Murray Steven P Wise 《Journal of neurophysiology》2002,87(1):631-633
Rhesus monkeys learned a series of conditional visuomotor associations involving two-dimensional "objects" that instructed one of three responses: tapping a touch screen, steady contact with the screen for a brief period, or steady contact for a longer period. Relative to controls, fornix-transected monkeys were impaired in the acquisition of new associations and in the retention of preoperatively learned ones. These findings challenge the view that the hippocampal system participates in associative learning only when spatial information is relevant to either the stimulus or the response. 相似文献
52.
Doris Škorić‐Milosavljević Fleur V. Y. Tjong Julien Barc Ad P. C. M. Backx Sally‐Ann B. Clur Karin van Spaendonck‐Zwarts Roelof‐Jan Oostra Najim Lahrouchi Leander Beekman Regina Bökenkamp Daniela Q. C. M. Barge‐Schaapveld Barbara J. Mulder Elisabeth M. Lodder Connie R. Bezzina Alex V. Postma 《American journal of medical genetics. Part A》2019,179(9):1836-1845
The first human mutations in GATA6 were described in a cohort of patients with persistent truncus arteriosus, and the phenotypic spectrum has expanded since then. This study underscores the broad phenotypic spectrum by presenting two patients with de novo GATA6 mutations, both exhibiting complex cardiac defects, pancreatic, and other abnormalities. Furthermore, we provided a detailed overview of all published human genetic variation in/near GATA6 published to date and the associated phenotypes (n = 78). We conclude that the most common phenotypes associated with a mutation in GATA6 were structural cardiac and pancreatic abnormalities, with a penetrance of 87 and 60%, respectively. Other common malformations were gallbladder agenesis, congenital diaphragmatic hernia, and neurocognitive abnormalities, mostly developmental delay. Fifty‐eight percent of the mutations were de novo, and these patients more often had an anomaly of intracardiac connections, an anomaly of the great arteries, and hypothyroidism, compared with those with inherited mutations. Functional studies mostly support loss‐of‐function as the pathophysiological mechanism. In conclusion, GATA6 mutations give a wide range of phenotypic defects, most frequently malformations of the heart and pancreas. This highlights the importance of detailed clinical evaluation of identified carriers to evaluate their full phenotypic spectrum. 相似文献
53.
Claus J. M?ller Anne Grete Byskov Jürgen Roth Julio E. Celis Elisabeth Bock 《Anatomy and embryology》1991,184(6):541-548
Summary The expression of theNeuralCell AdhesionMolecule, NCAM, in mouse gonads and ducts was studied from fetal life to maturity. The methods used were immunocytochemical staining and Western blotting. The immunocytochemical studies showed that the only structures that remain NCAM-positive throughout life were the mesonephric-derived rete ovarii and rete testis. Also in the fetal gonads some somatic cell lining the groups of differentiating germ cells were stained. In the immature as well as in the mature ovary the granulosa cells and oocytes of growing and large follicles — but not of small follicles — were stained. A particularly strong staining of the cytoplasm of the oocyte, healthy as well as atretic, was seen. All cells of the testis remained negative except for weakly stained residual bodies and late spermatids. At all ages the male ducts showed only weak staining, whereas in the female Müllerian duct the epithelium became strongly positive at puberty. The stroma of the Müllerian duct was positive during a transitory period around day 16 of fetal life in both sexes. One-dimensional gel immunoblotting of total protein from gonads, rete and ducts from immature and mature mice showed that only the two largest isoforms of NCAM (NCAM-A and NCAM-B) were present. The gonads and the rete of both sexes and the adult uterus expressed only NCAM-B, whereas NCAM-A was also detected in the adult epididymis. The present findings suggest that NCAM may be involved in the normal development and formation of both the gonads and ducts. In particular, NCAM may play a part in sustaining the integrity of the rete testis, thus ensuring the pathway for spermatozoa from the testis to the epididymis. Furthermore this cell adhesion molecule may also be important for follicular growth and differentiation. 相似文献
54.
Molecular determinants of human uveal melanoma invasion and metastasis 总被引:19,自引:0,他引:19
Seftor EA Meltzer PS Kirschmann DA Pe'er J Maniotis AJ Trent JM Folberg R Hendrix MJ 《Clinical & experimental metastasis》2002,19(3):233-246
The molecular analysis of cancer has benefited tremendously from the sequencing of the human genome integrated with the science
of bioinformatics. Microarray analysis technology has the potential to classify tumors based on the differential expression
of genes. In the current study, a collaborative, multidisciplinary approach was utilized to study the molecular determinants
of human uveal melanoma invasion and metastasis. Uveal melanoma is considered the most common primary intraocular cancer in
adults, resulting in the death of approximately 50% of patients affected. Unfortunately, at the time of diagnosis, many patients
already harbor microscopic metastases, thus underscoring a critical need to identify prognostic markers indicative of metastatic
potential. The investigative strategy consisted of isolating highly invasive vs. poorly invasive uveal melanoma cells from
a heterogeneous tumor derived from cells that had metastasized from the eye to the liver. The heterogeneous tissue explant
MUM-2 led to the derivation of two clonal cell lines: MUM-2B and MUM-2C. Further morphological and functional analyses revealed
that the MUM-2B cells were epithelioid, interconverted (expressing mesenchymal and epithelial phenotypes) highly invasive,
and demonstrated vasculogenic mimicry. The MUM-2C cells were spindle-like, expressed only a vimentin mesenchymal phenotype,
poorly invasive, and were incapable of vasculogenic mimicry. The molecular analysis of the MUM-2B vs. the MUM-2C clones resulted
in the differential expression of 210 known genes. Overall, the molecular signature of the MUM-2B cells resembled that of
multiple phenotypes – similar to a pluripotent, embryonic-like genotype. Validation of select genes that were upregulated
and down-regulated was conducted by semiquantitative RT-PCR measurement. This study provides a molecular profile that will
hopefully lead to the development of new molecular targets for therapeutic intervention and possible diagnostic markers to
predict the clinical outcome of patients with uveal melanoma.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
55.
56.
57.
Frequent polymorphism of the mitochondrial DNA polymerase gamma gene (POLG) in patients with normal spermiograms and unexplained subfertility 总被引:4,自引:0,他引:4
Jensen M Leffers H Petersen JH Nyboe Andersen A Jørgensen N Carlsen E Jensen TK Skakkebaek NE Rajpert-De Meyts E 《Human reproduction (Oxford, England)》2004,19(1):65-70
BACKGROUND: Male fertility largely depends on the quality of sperm production, which may be affected by environmental and genetic factors. In this study, we explored a possible role of the polymerase gamma (POLG) gene polymorphism, recently reported to be associated with male infertility in some populations. METHODS: The polymorphic CAG repeat (usually 10 codons long) in the POLG gene was studied in 1298 male subjects: 429 patients with infertility/subfertility, and 869 controls (495 men from the general population with unknown fertility and 374 recent fathers). In all subjects, the POLG polymorphism was assessed in relation to their semen quality, and--in the fertile controls--with biological fecundity measured as waiting time-to-pregnancy (TTP) for the couples. In the patients lacking the common POLG allele, the outcome of the assisted reproductive techniques (ART) for the couples was evaluated. RESULTS: The absence of one (10/ not equal to 10) or both common POLG alleles (not equal to 10/not equal to 10) was more frequent among the subfertile patients than among fertile controls (P=0.021 and P=0.04 respectively). The estimated predictive value for infertility in a man homozygous for the POLG polymorphism was 15.5% (95% CI: 4.8-51%). There was a positive association with sperm concentration: 14.3% of the normospermic subfertile patients were homozygous for the absence of the common POLG allele (not equal to 10/not equal to 10), in comparison with 2.3% of unselected controls (P=0.001) and 0.9% of the fertile men (P=0.0001). No association with sperm motility, morphology and TTP was found. Spermatozoa of the three not equal to 10/not equal to 10 patients treated with IVF retained the ability to penetrate the egg, but the fertilization rate was low. Nine homozygous not equal to 10/ not equal to 10 patients were treated with ICSI, resulting in pregnancy in seven couples. CONCLUSIONS: The POLG gene polymorphism should be considered as a possible contributing factor in patients with unexplained subfertility and normal spermiograms. The oocyte penetration ability of sperm may be partially impaired in the not equal to 10/not equal to 10 patients but most of them can be successfully treated with ICSI. 相似文献
58.
59.
High-frequency reactivation of X-linked genes in chinese hamster × human hybrid cells 总被引:5,自引:0,他引:5
Nathan Ellis Elisabeth Keitges Stanley M. Gartler Mariano Rocchi 《Somatic Cell and Molecular Genetics》1987,13(3):191-204
Three genes on the human inactive X chromosome retained in the Chinese hamster x human hybrid cell line X8/6T2 have been reactivated using the demethylating agent, 5-azacytidine (5-aza-CR). Pulse-labeling and histochemical methods permitted detection and measurement of reactivation rates of the hypoxanthine phosphoribosyltransferase (Hpt) and glucose-6-phosphate dehydrogenase (G6pd) genes within 48 h of treatment. About 50% of the cells became active for these genes, which represents a reactivation rate some 30-fold greater than previously reported in similar systems. The phosphoglycerate kinase (Pgk) gene was not reactivated as frequently as the Hptor G6pdgenes. Segregation analysis of progeny of treated cells showed that enzyme-positive and enzyme-negative cells were produced in proportions supporting the notion that 5-aza-CR causes demethylation by replicative loss and that demethylation leads to reactivation. 相似文献
60.
de Tychey C Spitz E Briançon S Lighezzolo J Girvan F Rosati A Thockler A Vincent S 《Journal of affective disorders》2005,85(3):323-326
BACKGROUND: The assessment of perinatal depressions and coping style. Methods: With depression scales (EPDS, GHQ.12) and Carver's BriefCope, the authors compared the prevalence rates of pre and postnatal depression in a cohort of 277 French women. RESULTS: Their work revealed very high levels of prenatal depression (almost 20%) and less important but nonetheless sizeable rates (11%) of postnatal depression, making such perinatal depressions a major public health concern. The coping styles proposed in Carver's public health BriefCope questionnaire make it possible to significantly differentiate during these two periods between depressive women and their non-depressed counterparts. CONCLUSIONS: This enables us to underline factors of risk and protection suggesting the importance of setting up compensatory and preventive systems and evaluating their pertinence in the framework of future research. 相似文献