다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Living in an oxygenated environment has required the evolution of effective cellular strategies to detect and detoxify metabolites of molecular oxygen known as reactive oxygen species. Here we review evidence that the appropriate and inappropriate production of oxidants, together with the ability of organisms to respond to oxidative stress, is intricately connected to ageing and life span.

Oxidants, oxidative stress and the biology of ageing.

The transforming growth factor beta (TGF-beta) family of growth factors control the development and homeostasis of most tissues in metazoan organisms. Work over the past few years has led to the elucidation of a TGF-beta signal transduction network. This network involves receptor serine/threonine kinases at the cell surface and their substrates, the SMAD proteins, which move into the nucleus, where they activate target gene transcription in association with DNA-binding partners. Distinct repertoires of receptors, SMAD proteins, and DNA-binding partners seemingly underlie, in a cell-specific manner, the multifunctional nature of TGF-beta and related factors. Mutations in these pathways are the cause of various forms of human cancer and developmental disorders.

TGF-beta signal transduction.

Motivation: Homology models of proteins are of great interest for planning and analysing biological experiments when no experimental three-dimensional structures are available. Building homology models requires specialized programs and up-to-date sequence and structural databases. Integrating all required tools, programs and databases into a single web-based workspace facilitates access to homology modelling from a computer with web connection without the need of downloading and installing large program packages and databases.

Results: SWISS-MODEL workspace is a web-based integrated service dedicated to protein structure homology modelling. It assists and guides the user in building protein homology models at different levels of complexity. A personal working environment is provided for each user where several modelling projects can be carried out in parallel. Protein sequence and structure databases necessary for modelling are accessible from the workspace and are updated in regular intervals. Tools for template selection, model building and structure quality evaluation can be invoked from within the workspace. Workflow and usage of the workspace are illustrated by modelling human Cyclin A1 and human Transmembrane Protease 3.

Availability: The SWISS-MODEL workspace can be accessed freely at http://swissmodel.expasy.org/workspace/

Contact: Torsten.Schwede@unibas.ch

Supplementary information: Supplementary data are available at Bioinformatics online.

/pdf/the-swiss-model-workspace-a-web-based-environment-for-1jba36oddx.pdf

The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling

Growth factors synthesized by ovarian somatic cells directly affect oocyte growth and function, but it is unclear whether oocyte-secreted factors play a reciprocal role in modulating somatic cell functions in vivo. During the functional analysis of members of the transforming growth factor-beta superfamily in mouse development, we have uncovered a new family member, growth differentiation factor-9 (GDF-9), which is required for ovarian folliculogenesis. GDF-9 messenger RNA is synthesized only in the oocyte from the primary one-layer follicle stage until after ovulation. Here we analyse ovaries from GDF-9-deficient female mice and demonstrate that primordial and primary one-layer follicles can be formed, but there is a block in follicular development beyond the primary one-layer follicle stage which leads to complete infertility. Oocyte growth and zona pellucida formation proceed normally, but other aspects of oocyte differentiation are compromised. Thus, GDF-9 is the first oocyte-derived growth factor required for somatic cell function in vivo.

Growth differentiation factor-9 is required during early ovarian folliculogenesis

Follicle stimulating hormone (FSH) is a member of the glycoprotein hormone family that includes luteinzing hormone (LH), thyroid stimulating hormone, and chorionic gonadotropin. These heterodimeric hormones share a common alpha subunit and differ in their hormone-specific beta subunit. The biological activity is conferred only by the heterodimers. FSH and LH are synthesized in the same cells of the pituitary, the gonadotrophs. FSH receptors are localized to Sertoli cells of the testes and granulosa cells of the ovary. Minimal data has been accumulated so far involving human mutations in the FSH beta, LH beta, or the gonadotropin receptor genes. There are no known mouse strains with mutations in the FSH beta gene. To generate animal models for human diseases involving the gonadotropin signal transduction pathway, we produced mice deficient in the FSH beta subunit and therefore in FSH using ES cell technology. FSH-deficient females are infertile due to a block in folliculogenesis prior to antral follicle formation. Although FSH was predicted to be necessary for spermatogenesis and Sertoli cell growth in males, FSH-deficient males are fertile despite having small testes. Our findings have important implications for male contraceptive development in humans.

Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility.

Manganese superoxide dismutase (SOD2) converts superoxide to oxygen plus hydrogen peroxide and serves as the primary defense against mitochondrial superoxide. Impaired SOD2 activity in humans has been associated with several chronic diseases, including ovarian cancer and type I diabetes, and SOD2 overexpression appears to suppress malignancy in cultured cells. We have produced a line of SOD2 knockout mice (SOD2m1BCM/SOD2m1BCM) that survive up to 3 weeks of age and exhibit several novel pathologic phenotypes including severe anemia, degeneration of neurons in the basal ganglia and brainstem, and progressive motor disturbances characterized by weakness, rapid fatigue, and circling behavior. In addition, SOD2m1BCM/SOD2m1BCM mice older than 7 days exhibit extensive mitochondrial injury within degenerating neurons and cardiac myocytes. Approximately 10% of SOD2m1BCM/SOD2m1BCM mice exhibit markedly enlarged and dilated hearts. These observations indicate that SOD2 deficiency causes increased susceptibility to oxidative mitochondrial injury in central nervous system neurons, cardiac myocytes, and other metabolically active tissues after postnatal exposure to ambient oxygen concentrations. Our SOD2-deficient mice differ from a recently described model in which homozygotes die within the first 5 days of life with severe cardiomyopathy and do not exhibit motor disturbances, central nervous system injury, or ultrastructural evidence of mitochondrial injury.

https://www.pnas.org/content/pnas/93/18/9782.full.pdf

Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice.

The development of social familiarity in rodents depends predominantly on olfactory cues and can critically influence reproductive success. Researchers have operationally defined this memory by a reliable decrease in olfactory investigation in repeated or prolonged encounters with a conspecific. Brain oxytocin (OT) and vasopressin (AVP) seem to modulate a range of social behaviour from parental care to mate guarding. Pharmacological studies indicate that AVP administration may enhance social memory, whereas OT administration may either inhibit or facilitate social memory depending on dose, route or paradigm. We found that male mice mutant for the oxytocin gene (Oxt-/-) failed to develop social memory, whereas wild-type (Oxt+/+) mice showed intact social memory. Measurement of both olfactory foraging and olfactory habituation tasks indicated that olfactory detection of non-social stimuli is intact in Oxt-/- mice. Spatial memory and behavioural inhibition measured in a Morris water-maze, Y-maze, or habituation of an acoustic startle also seemed intact. Treatment with OT but not AVP rescued social memory in Oxt-/- mice, and treatment with an OT antagonist produced a social amnesia-like effect in Oxt+/+ mice. Our data indicate that OT is necessary for the normal development of social memory in mice and support the hypothesis that social memory has a neural basis distinct from other forms of memory.

/pdf/social-amnesia-in-mice-lacking-the-oxytocin-gene-3foyz0bav1.pdf

Social amnesia in mice lacking the oxytocin gene.

The inhibins are α:β heterodimeric growth factors that are members of the transforming growth factor-β family To understand the physiological roles of the inhibins in mammalian development and reproduction, a targeted deletion of the α-inhibin gene was generated by homologous recombination in mouse embryonic stem cells Mice homozygous for the null allele (inhibin-deficient) initially develop normally but every mouse ultimately develops mixed or incompletely differentiated gonadal stromal tumours either unilaterally or bilaterally Inhibin is thus a critical negative regulator of gonadal stromal cell proliferation and the first secreted protein identified to have tumour-suppressor activity

Martin M. Matzuk

Papers

Growth differentiation factor-9 is required during early ovarian folliculogenesis

Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility.

Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice.

Social amnesia in mice lacking the oxytocin gene.

Alpha-inhibin is a tumour-suppressor gene with gonadal specificity in mice.