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Distinct Steps (distinct + step)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	33%

Selected Abstracts

Organ-specific lymphangiectasia, arrested lymphatic sprouting, and maturation defects resulting from gene-targeting of the PI3K regulatory isoforms p85,, p55,, and p50,

DEVELOPMENTAL DYNAMICS, Issue 10 2009
Carla Mouta-Bellum
Abstract The phosphoinositide 3-kinase (PI3K) family has multiple vascular functions, but the specific regulatory isoform supporting lymphangiogenesis remains unidentified. Here, we report that deletion of the Pik3r1 gene, encoding the regulatory subunits p85,, p55,, and p50, impairs lymphatic sprouting and maturation, and causes abnormal lymphatic morphology, without major impact on blood vessels. Pik3r1 deletion had the most severe consequences among gut and diaphragm lymphatics, which share the retroperitoneal anlage, initially suggesting that the Pik3r1 role in this vasculature is anlage-dependent. However, whereas lymphatic sprouting toward the diaphragm was arrested, lymphatics invaded the gut, where remodeling and valve formation were impaired. Thus, cell-origin fails to explain the phenotype. Only the gut showed lymphangiectasia, lymphatic up-regulation of the transforming growth factor-, co-receptor endoglin, and reduced levels of mature vascular endothelial growth factor-C protein. Our data suggest that Pik3r1 isoforms are required for distinct steps of embryonic lymphangiogenesis in different organ microenvironments, whereas they are largely dispensable for hemangiogenesis. Developmental Dynamics 238:2670,2679, 2009. © 2009 Wiley-Liss, Inc. [source]

PI3K-FRAP/mTOR pathway is critical for hepatocyte proliferation whereas MEK/ERK supports both proliferation and survival

HEPATOLOGY, Issue 5 2002
Alexandre Coutant
Growth factors are known to favor both proliferation and survival of hepatocytes. In this work, we investigated the role of 2 main signaling pathways, phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MEK)/extracellular signal,regulated kinase (ERK), in these processes. First, evidence was provided that the PI3K cascade as well as the MEK/ERK cascade is a key transduction pathway controlling hepatocyte proliferation, as ascertained by arrest of DNA synthesis in the presence of LY294002, a specific PI3K inhibitor. Inhibition of FRAP/mTOR by rapamycin also abrogated DNA replication and protein synthesis induced by growth factor. We showed that expression of cyclin D1 at messenger RNA (mRNA) and protein levels was regulated by this pathway. We highlighted that 4E-BP1 phosphorylation was not activated by epidermal growth factor (EGF) but was under an insulin-regulation mechanism through a PI3K-FRAP/mTOR activation that could account for the permissive role of insulin on hepatocyte proliferation. No interference between the MEK/ERK pathway and 4E-BP1 phosphorylation was detected, whereas p70S6K phosphorylation induced by EGF was under a U0126-sensitive regulation. Last, we established that the antiapoptotic function of EGF was dependent on MEK, whereas LY294002 and rapamycin had no direct effect on cell survival. Taken together, these data highlight the regulation and the role of 2 pathways that mediate growth-related response by acting onto distinct steps. In conclusion, hepatocyte progression in late G1 phase induced by EGF generates survival signals depending on MEK activation, whereas PI3K and MEK/ERK cascades are both necessary for hepatocyte replication. [source]

In vitro and in vivo studies on the generation of the primary T-cell receptor repertoire

IMMUNOLOGICAL REVIEWS, Issue 1 2004
Ferenc Livák
Summary:, The primary T-cell receptor repertoire is generated by somatic rearrangement of discontinuous gene segments. The shape of the combinatorial repertoire is stereotypical and, in part, evolutionarily conserved among mammals. Rearrangement is initiated by specific interactions between the recombinase and the recombination signals (RSs) that flank the gene segments. Conserved sequence variations in the RS, which modulate its interactions with the recombinase, appear to be a major factor in shaping the primary repertoire. In vitro, biochemical studies have revealed distinct steps in these complex recombinase,RS interactions that may determine the final frequency of gene segment rearrangement. These studies offer a plausible model to explain gene segment selection, but new, more physiological approaches will have to be developed to verify and refine the mechanism by which the recombinase targets the RS in its endogenous chromosomal context in vivo. [source]

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells.

MICROSCOPY RESEARCH AND TECHNIQUE, Issue 4 2010
Part 2: Changes in spermatid organelles associated with development of spermatozoa
Abstract Spermiogenesis is a long process whereby haploid spermatids derived from the meiotic divisions of spermatocytes undergo metamorphosis into spermatozoa. It is subdivided into distinct steps with 19 being identified in rats, 16 in mouse and 8 in humans. Spermiogenesis extends over 22.7 days in rats and 21.6 days in humans. In this part, we review several key events that take place during the development of spermatids from a structural and functional point of view. During early spermiogenesis, the Golgi apparatus forms the acrosome, a lysosome-like membrane bound organelle involved in fertilization. The endoplasmic reticulum undergoes several topographical and structural modifications including the formation of the radial body and annulate lamellae. The chromatoid body is fully developed and undergoes structural and functional modifications at this time. It is suspected to be involved in RNA storing and processing. The shape of the spermatid head undergoes extensive structural changes that are species-specific, and the nuclear chromatin becomes compacted to accommodate the stream-lined appearance of the sperm head. Microtubules become organized to form a curtain or manchette that associates with spermatids at specific steps of their development. It is involved in maintenance of the sperm head shape and trafficking of proteins in the spermatid cytoplasm. During spermiogenesis, many genes/proteins have been implicated in the diverse dynamic events occurring at this time of development of germ cells and the absence of some of these have been shown to result in subfertility or infertility. Microsc. Res. Tech., 2010. © 2009 Wiley-Liss, Inc. [source]

Sperm-mediated gene transfer: Applications and implications

BIOESSAYS, Issue 5 2005
Kevin Smith
Recent developments in studies of sperm-mediated gene transfer (SMGT) now provide solid ground for the notion that sperm cells can act as vectors for exogenous genetic sequences. A substantive body of evidence indicates that SMGT is potentially useable in animal transgenesis, but also suggests that the final fate of the exogenous sequences transferred by sperm is not always predictable. The analysis of SMGT-derived offspring has shown the existence of integrated foreign sequences in some cases, while in others stable modifications of the genome are difficult to detect. The appearance of SMGT-derived modified offspring on the one hand and, on the other hand, the rarity of actual modification of the genome, suggest inheritance as extrachromosomal structures. Several specific factors have been identified that mediate distinct steps in SMGT. Among those, a prominent role is played by an endogenous reverse transcriptase of retrotransposon origin. Mature spermatozoa are naturally protected against the intrusion of foreign nucleic acid molecules; however, particular environmental conditions, such as those occurring during human assisted reproduction, can abolish this protection. The possibility that sperm cells under these conditions carry genetic sequences affecting the integrity or identity of the host genome should be critically considered. These considerations further suggest the possibility that SMGT events may occasionally take place in nature, with profound implications for evolutionary processes. BioEssays 27: 551,562, 2005. © 2005 Wiley periodicals, Inc. [source]

Structural and Magnetic Resolution of a Two-Step Full Spin-Crossover Transition in a Dinuclear Iron(II) Pyridyl-Bridged Compound

CHEMISTRY - A EUROPEAN JOURNAL, Issue 32 2006
Jarrod J. M. Amoore
Abstract A dinuclear iron(II) complex containing the new pyridyl bridging ligand, 2,5-di(2,,2,,-dipyridylamino)pyridine (ddpp) has been synthesised and characterised by single-crystal X-ray diffraction, magnetic susceptibility and Mössbauer spectral methods. This compound, [Fe2(ddpp)2(NCS)4],4,CH2Cl2, undergoes a two-step full spin crossover. Structural analysis at each of the three plateau temperatures has revealed a dinuclear molecule with spin states HS,HS, HS,LS and LS,LS (HS: high spin, LS: low spin) for the two iron(II) centres. This is the first time that resolution of the metal centres in a HS,LS ordered state has been achieved in a two-step dinuclear iron(II) spin-crossover compound. Thermogravimetric data show that the dichloromethane solvate molecules can be removed in two distinct steps at 120,°C and 200,°C. The partially de-solvated clathrate, [Fe2(ddpp)2(NCS)4],CH2Cl2, undergoes a one-step transition with an increased transition temperature with respect to the as synthesised material. Structural characterisation of this material reveals subtle changes to the coordination geometries at each of the iron(II) centres and striking changes to the local environment of the dinuclear complex. The fully de-solvated material remains high spin over all temperatures. Interestingly, the solvent can be re-introduced into the monosolvated solid to achieve complete conversion back to the original two-step crossover material, [Fe2(ddpp)2(NCS)4],4,CH2Cl2. [source]