Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: CELL-MIGRATION ; ACTIN CYTOSKELETON ; EPIDERMAL-GROWTH-FACTOR ; PROTEOMIC ANALYSIS ; TUMOR-SUPPRESSOR ; ALPHA-5-BETA-1 INTEGRIN ; COATED PITS ; RECEPTOR-MEDIATED ENDOCYTOSIS ; MOTOR PROTEINS ; LYSOSOMAL DEGRADATION
    Abstract: alpha2beta1 integrin is one of the most important collagen-binding receptors, and it has been implicated in numerous thrombotic and immune diseases. alpha2beta1 integrin is a potent tumour suppressor, and its downregulation is associated with increased metastasis and poor prognosis in breast cancer. Currently, very little is known about the mechanism that regulates the cell-surface expression and trafficking of alpha2beta1 integrin. Here, using a quantitative fluorescence-microscopy-based RNAi assay, we investigated the impact of 386 cytoskeleton-associated or -regulatory genes on alpha2 integrin endocytosis and found that 122 of these affected the intracellular accumulation of alpha2 integrin. Of these, 83 were found to be putative regulators of alpha2 integrin trafficking and/or expression, with no observed effect on the internalization of epidermal growth factor (EGF) or transferrin. Further interrogation and validation of the siRNA screen revealed a role for KIF15, a microtubule-based molecular motor, as a significant inhibitor of the endocytic trafficking of alpha2 integrin. Our data suggest a novel role for KIF15 in mediating plasma membrane localization of the alternative clathrin adaptor Dab2, thus impinging on pathways that regulate alpha2 integrin internalization.
    Type of Publication: Journal article published
    PubMed ID: 24659801
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: RECEPTOR ; GENES ; NERVOUS-SYSTEM ; MICROTUBULE DYNAMICS ; POLARITY ; MOTILITY ; EGF ; GENOMIC LANDSCAPES ; NEURON NAVIGATOR ; NAV3
    Abstract: Dissemination of primary tumor cells depends on migratory and invasive attributes. Here, we identify Navigator-3 (NAV3), a gene frequently mutated or deleted in human tumors, as a regulator of epithelial migration and invasion. Following induction by growth factors, NAV3 localizes to the plus ends of microtubules and enhances their polarized growth. Accordingly, NAV3 depletion trimmed microtubule growth, prolonged growth factor signaling, prevented apoptosis and enhanced random cell migration. Mathematical modeling suggested that NAV3-depleted cells acquire an advantage in terms of the way they explore their environment. In animal models, silencing NAV3 increased metastasis, whereas ectopic expression of the wild-type form, unlike expression of two, relatively unstable oncogenic mutants from human tumors, inhibited metastasis. Congruently, analyses of 〉 2,500 breast and lung cancer patients associated low NAV3 with shorter survival. We propose that NAV3 inhibits breast cancer progression by regulating microtubule dynamics, biasing directionally persistent rather than random migration, and inhibiting locomotion of initiated cells.
    Type of Publication: Journal article published
    PubMed ID: 25678558
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: INVASION ; PATHWAY ; GROWTH-FACTOR RECEPTOR ; endocytosis ; CELL-MIGRATION ; TUMOR-METASTASIS ; ACTIN ; SRC ; INVADOPODIA FORMATION ; PODOSOMES
    Abstract: Amplified HER2, which encodes a member of the epidermal growth factor receptor (EGFR) family, is a target of effective therapies against breast cancer. In search for similarly targetable genomic aberrations, we identified copy number gains in SYNJ2, which encodes the 5'-inositol lipid phosphatase synaptojanin 2, as well as overexpression in a small fraction of human breast tumors. Copy gain and overexpression correlated with shorter patient survival and a low abundance of the tumor suppressor microRNA miR-31. SYNJ2 promoted cell migration and invasion in culture and lung metastasis of breast tumor xenografts in mice. Knocking down SYNJ2 impaired the endocytic recycling of EGFR and the formation of cellular lamellipodia and invadopodia. Screening compound libraries identified SYNJ2-specific inhibitors that prevented cell migration but did not affect the related neural protein SYNJ1, suggesting that SYNJ2 is a potentially druggable target to block cancer cell migration.
    Type of Publication: Journal article published
    PubMed ID: 25605973
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The nucleotide sequence has been determined for the Streptococcus mutans wall-associated protein A (wapA) gene from serotype c strains Ingbritt and GS5. The nucleotide sequence for each wapA gene was virtually identical, although the gene from strain GS5 contained a 24 base pair deletion. A 29 amino acid signal peptide was specified by each wapA gene with a mature protein of 424 amino acids (Mr, 45276) for strain Ingbritt and 416 amino acids (Mr, 44846) for strain GS5. In the C-terminal region of the wall-associated protein A, considerable sequence similarity was found with the membrane anchor region of proteins from other Gram-positive organisms such as the group A streptococcal M protein and the group G streptococcal IgG binding protein. Adjacent to the proposed membrane anchor is a highly hydrophilic region which may span the cell wall; both sequence data and experimental evidence indicate the existence of a region immediately outside the wall at which proteolytic cleavage occurs to release antigen A of Mr 29000 into the culture supernatant. Thus, the wall-associated protein A is a precursor of the 29000 Mr antigen A.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    ISSN: 1432-1076
    Keywords: Mechanical ventilation ; Paediatric intensive care ; Positive end expiratory pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of varying the positive end expiratory pressure (PEEP) level during mechanical ventilation has been assessed in ten children with liver disease, mean age 3.8 years. PEEP was increased 3 cmH2O above the child's original (baseline) PEEP level and then decreased either by 3 cmH2O below the baseline or to 0 cmH2O. In all ten children increasing the PEEP above the baseline improved oxygenation; in the group overall the medianPaO2 increased from 90 mmHg to 97mmHg (P〈0.01). In eight of the ten children decreasing the PEEP level below the baseline resulted in a deterioration in oxygenation; in the group overall the medianPaO2 decreased from 91 mmHg to 82 mmHg (P〈0.05). Changes in PEEP levels, however, did not result in clinically significant alterations inPaCO2, heart rate or blood pressure. We conclude that modest increases in PEEP are well tolerated in children with liver disease and result in an improvement in oxygenation.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    ISSN: 1432-1106
    Keywords: cochlear nucleus ; auditory physiology ; sensory coding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary When poststimulus time histograms are computed for tone-burst stimulation, certain shapes of histograms, or response patterns, were more often observed than others for units in the cochlear nucleus. The shapes of patterns that are observed depend upon stimulus parameters. These response patterns of units in the cochlear nucleus lend themselves to classification into categories; a given group of units has not only response patterns in common but often also other properties.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    ISSN: 1433-2965
    Keywords: Key words:Bisphosphonates – Glucocorticoid-induced osteoporosis – Rheumatoid arthritis – Risedronate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: The aim of the study was to assess risedronate’s effect on bone mineral density in postmenopausal women with rheumatoid arthritis receiving glucocorticoids. We carried out a two center, 2 year, double-masked, placebo-controlled trial with a third year of nontreatment follow-up. We studied 120 women requiring long-term glucocorticoid therapy at 〉2.5 mg/day prednisolone randomized to treatment with daily placebo; daily 2.5 mg risedronate; or cyclical 15 mg risedronate (2 out of 12 weeks). At 97 weeks, bone mineral density was maintained at the lumbar spine (+1.4%) and trochanter (+0.4%) in the daily 2.5 mg risedronate group, while significant bone loss occurred in the placebo group (–1.6%, p= 0.03; and 4.0%, p〈0.005, respectively). At the femoral neck, there was a nonsignificant bone loss in the daily 2.5 mg risedronate group (–1.0%) while in the placebo group bone mass decreased significantly (–3.6%, p〈0.001). The difference between placebo and daily 2.5 mg risedronate groups was significant at the lumbar spine (p= 0.009) and trochanter (p= 0.02) but did not reach statistical significance at the femoral neck. Although not significantly different from placebo at the lumbar spine, the overall effect of the cyclical regimen was similar to that of the daily 2.5 mg risedronate regimen. Treatment withdrawal led to bone loss in the risedronate groups that was significant at the lumbar spine. A similar number of patients experienced adverse events (including upper gastrointestinal events) across treatment groups and risedronate was generally well tolerated. Thus risedronate preserves bone mass in postmenopausal women with rheumatoid arthritis receiving glucocorticoids while patients receiving a placebo have significant bone loss.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    ISSN: 1433-2965
    Keywords: Bone remodelling ; Collagen ; Osteocalcin ; Osteoporosis ; Pyridinium crosslinks
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aims of the study were to evaluate the use of bone-specific biochemical markers of turnover in type I osteoporosis, to test for evidence of heterogeneity of bone turnover in this condition, and to attempt to devise an ‘uncoupling index’ by using the relationship between bone-specific biochemical markers of bone formation and bone resorption. In women with type I osteoporosis (mean age 64 years, SD 5;n=63) the mean level of serum osteocalcin, a specific biochemical marker of bone formation, was 9.9 ng/ml (SD 2.0), which was higher than the level in normal postmenopausal women (mean age 65 years, SD 6;n=8.9 ng/ml (SD 2.0;p〈0.01). The variance of serum osteocalcin levels in the two groups was similar. Compared with this 11% increase in the biochemical marker for bone formation, the markers of bone resorption, total urinary deoxypyridinoline (bone-specific), pyridinoline and hydroxyproline were increased by 40% (p〈0.0001), 61% (p〈0.0001) and 25% (p〈0.01), respectively. Furthermore, these biochemical markers of bone resorption had greater variance in women in type I osteoporosis than in the normal postmenopausal women (p〈0.001). The urinary excretion of the free crosslinks deoxypyridinoline, pyridinoline and glycosylated pyridinoline were increased by 26% (p〈0.001), 17% (p〈0.01) and 13% (NS) respectively. An ‘uncoupling index’ was calculated for the difference between urinary deoxypyridinoline and serum osteocalcin using the results from the normal women and expressed asz-scores. We conclude that the pyridinium crosslinks of collagen enable better discrimination between normal and osteoporotic women than does hydroxyproline. In osteoporosis there appears to be heterogeneity of bone resorption. Finally, an uncoupling index indicated that in osteoporosis bone resorption was increased to a greater extent than bone formation as compared with normal postmenopausal women.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    ISSN: 1433-2965
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    ISSN: 1432-8798
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two serological tests were used to examine the antigenic relationships between murine hepatitis viruses that cause different diseases in mice. Antisera prepared by immunization of mice with the individual viruses were tested for their ability to neutralize both the homologous immunogen and the other viruses. By a plaque reduction neutralization test, each antiserum was found to be specific for the immunizing virus; however, there was substantial cross-reactivity, indicating the viruses were closely related. By kinetic neutralization, two of the viruses tested, MHV-JHM and MHV-2, were found to be antigenically distinct. MHV-3 and MHV-A59 were found to be antigenically very similar but distinct. These data show that kinetic neutralization is a more precise method for determining the antigenic relationships between murine coronaviruses.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...