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1.
Glucose/galactose malabsorption (GGM) is an autosomal recessive disease manifesting within the first weeks of life and characterized by a selective failure to absorb dietary glucose and galactose from the intestine. The consequent severe diarrhoea and dehydration are usually fatal unless these sugars are eliminated from the diet. Intestinal biopsies of GGM patients have revealed a specific defect in Na(+)-dependent absorption of glucose in the brush border. Normal glucose absorption is mediated by the Na+/glucose cotransporter in the brush border membrane of the intestinal epithelium. Cellular influx is driven by the transmembrane Na+ electrochemical potential gradient; thereafter the sugar moves to the blood across the basolateral membrane via the facilitated glucose carrier. We have previously cloned and sequenced a Na+/glucose cotransporter from normal human ileum and shown that this gene, SGLT1, resides on the distal q arm of chromosome 22. We have now amplified SGLT1 complementary DNA and genomic DNA from members of a family affected with GGM by the polymerase chain reaction. Sequence analysis of the amplified products has revealed a single missense mutation in SGLT1 which cosegregates with the GGM phenotype and results in a complete loss of Na(+)-dependent glucose transport in Xenopus oocytes injected with this complementary RNA. 相似文献
2.
Zhang J Gray J Wu L Leone G Rowan S Cepko CL Zhu X Craft CM Dyer MA 《Nature genetics》2004,36(4):351-360
The retinoblastoma protein (Rb) regulates proliferation, cell fate specification and differentiation in the developing central nervous system (CNS), but the role of Rb in the developing mouse retina has not been studied, because Rb-deficient embryos die before the retinas are fully formed. We combined several genetic approaches to explore the role of Rb in the mouse retina. During postnatal development, Rb is expressed in proliferating retinal progenitor cells and differentiating rod photoreceptors. In the absence of Rb, progenitor cells continue to divide, and rods do not mature. To determine whether Rb functions in these processes in a cell-autonomous manner, we used a replication-incompetent retrovirus encoding Cre recombinase to inactivate the Rb1(lox) allele in individual retinal progenitor cells in vivo. Combined with data from studies of conditional inactivation of Rb1 using a combination of Cre transgenic mouse lines, these results show that Rb is required in a cell-autonomous manner for appropriate exit from the cell cycle of retinal progenitor cells and for rod development. 相似文献
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Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas 总被引:1,自引:0,他引:1
Wu G Broniscer A McEachron TA Lu C Paugh BS Becksfort J Qu C Ding L Huether R Parker M Zhang J Gajjar A Dyer MA Mullighan CG Gilbertson RJ Mardis ER Wilson RK Downing JR Ellison DW Zhang J Baker SJ;St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project 《Nature genetics》2012,44(3):251-253
To identify somatic mutations in pediatric diffuse intrinsic pontine glioma (DIPG), we performed whole-genome sequencing of DNA from seven DIPGs and matched germline tissue and targeted sequencing of an additional 43 DIPGs and 36 non-brainstem pediatric glioblastomas (non-BS-PGs). We found that 78% of DIPGs and 22% of non-BS-PGs contained a mutation in H3F3A, encoding histone H3.3, or in the related HIST1H3B, encoding histone H3.1, that caused a p.Lys27Met amino acid substitution in each protein. An additional 14% of non-BS-PGs had somatic mutations in H3F3A causing a p.Gly34Arg alteration. 相似文献
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Gordon Dyer 《Systemic Practice and Action Research》2004,17(4):307-321
Contemporary systems activity can be divided into that stressing feasible and practical short-term measures, and that which is more ideal-aware, focussed on mid-longer term futures, and typically involving on-going community or social systems design. The paper highlights the key differences in approach, but then invites closer collaboration in the cause of the possible contribution that systems thinking could make for a longer term future, with Y3K (Year 3000) as a metaphor for this. This analysis, which derives from work undertaken at Asilomar 1995 and Fuschl conversations in 2000 and 2002, finds that contemporary social system design, which is driven by western culture and is action-oriented, needs adaptation before it could contribute to greater future global harmony. A truly comprehensive systems design process must accommodate a wide range of possible parameters in terms of culture, and appreciation of time and progress. An emerging paradigm as basis for thinking and engaging in social systems design work of the future is offered, which also has relevance to general systems practice. 相似文献
6.
Floral colour signals are used by pollinators as predictors of nutritional rewards, such as nectar. But as insect pollinators often need to invest energy to maintain their body temperature above the ambient temperature, floral heat might also be perceived as a reward. Here we show that bumblebees (Bombus terrestris) prefer to visit warmer flowers and that they can learn to use colour to predict floral temperature before landing. In what could be a widespread floral adaptation, plants may modulate their temperature to encourage pollinators to visit. 相似文献
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Rieger syndrome, an autosomal dominant disorder, includes ocular, craniofacial and umbilical abnormalities. The pitx2 homeobox gene, which is mutated in Rieger syndrome, has been proposed to be the effector molecule interpreting left-right axial information from the early embryonic trunk to each organ. Here we have used gene targeting in mice to generate a loss-of-function allele that would be predicted to result in organ randomization or isomerization. Although pitx2-/- embryos had abnormal cardiac morphogenesis, mutant hearts looped in the normal direction. Pitx2-/- embryos had correctly oriented, but arrested, embryonic rotation and right pulmonary isomerism. They also had defective development of the mandibular and maxillary facial prominences, regression of the stomodeum and arrested tooth development. Fgf8 expression was absent, and Bmp4 expression was expanded in the branchial-arch ectoderm. These data reveal a critical role for pitx2 in left-right asymmetry but indicate that pitx2 may function at an intermediate step in cardiac morphogenesis and embryonic rotation. 相似文献
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Gordon Dyer 《Systemic Practice and Action Research》1993,6(4):407-419
Collaboration and cooperation within the systems community require a facility to aid recognition and appreciation of how individual contributions fit into the totality of systems practice. A framework to help in this is suggested, linked to characteristic concepts and techniques of three identified generations of systems approaches-two derived from a management-linked systems practice in the 1970s and late 1980s, the third from new attempts to design a better future. 相似文献
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Sperm competition between Drosophila males involves both displacement and incapacitation. 总被引:4,自引:0,他引:4
Females in almost all animal groups copulate with multiple males. This behaviour allows different males to compete for fertilization and gives females the opportunity to mediate this competition. In many animals and most insects, the second male to copulate with a female typically sires most of her offspring. In Drosophila melanogaster, this second-male sperm precedence has long been studied but, as in most species, its mechanism has remained unknown. Here we show, using labelled sperm in doubly mated females, that males can both physically displace and incapacitate stored sperm from earlier-mating males. Displacement occurs only if the second male transfers sperm to the female, and in only one of her three sperm-storage organs. Incapacitation can be caused by either fertile or spermless second males, but requires extended intervals between matings. Sperm from different males are not 'stratified' in the storage organs but mix freely. Many animal species may have multiple mechanisms of sperm competition like those observed here, and revealing these mechanisms is necessary to understand the genetic and evolutionary basis of second-male sperm precedence in animals. 相似文献
10.
Laurie NA Donovan SL Shih CS Zhang J Mills N Fuller C Teunisse A Lam S Ramos Y Mohan A Johnson D Wilson M Rodriguez-Galindo C Quarto M Francoz S Mendrysa SM Guy RK Marine JC Jochemsen AG Dyer MA 《Nature》2006,444(7115):61-66
Most human tumours have genetic mutations in their Rb and p53 pathways, but retinoblastoma is thought to be an exception. Studies suggest that retinoblastomas, which initiate with mutations in the gene retinoblastoma 1 (RB1), bypass the p53 pathway because they arise from intrinsically death-resistant cells during retinal development. In contrast to this prevailing theory, here we show that the tumour surveillance pathway mediated by Arf, MDM2, MDMX and p53 is activated after loss of RB1 during retinogenesis. RB1-deficient retinoblasts undergo p53-mediated apoptosis and exit the cell cycle. Subsequently, amplification of the MDMX gene and increased expression of MDMX protein are strongly selected for during tumour progression as a mechanism to suppress the p53 response in RB1-deficient retinal cells. Our data provide evidence that the p53 pathway is inactivated in retinoblastoma and that this cancer does not originate from intrinsically death-resistant cells as previously thought. In addition, they support the idea that MDMX is a specific chemotherapeutic target for treating retinoblastoma. 相似文献