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Biomedical subjects

A Iacoangeli

Publications and source records attributed to A Iacoangeli.

13 recordsLinked to original sources
PubMed2002

Molecular characterization and action of usnic acid: a drug that inhibits proliferation of mouse polyomavirus in vitro and whose main target is RNA transcription.

Usnic acid is a normal component of lichen cells. This natural compound has shown different biological and physiological activities that might have a great relevance in pharmacology and clinics. For instance, usnic acid is known for its antibacterial and antiparasitic action. Also, the drug has a potential interest in cancer therapy because of its antimitotic and antiproliferative action. The molecular structure of usnic acid has been validated and further explored in this investigation. Many biological properties of this drug are known; however its potential antiviral action has not yet been evaluated. In this paper, we demonstrate that usnic acid is a potent inhibitor of the proliferation of mouse polyomavirus. Its action is not exerted at the level of virion entry into the host cell. Moreover, the abolition of viral DNA replication is an indirect consequence of the drastic inhibition of RNA transcription.

Actins↗
PubMed2001

Cosmology from MAXIMA-1, BOOMERANG, and COBE DMR cosmic microwave background observations.

Recent results from BOOMERANG-98 and MAXIMA-1, taken together with COBE DMR, provide consistent and high signal-to-noise measurements of the cosmic microwave background power spectrum at spherical harmonic multipole bands over 2<l less similar to 800. Analysis of the combined data yields 68% (95%) confidence limits on the total density, Omega(tot) approximately 1.11+/-0.07 (+0.13)(-0.12), the baryon density, Omega(b)h(2) approximately 0.032(+0.005)(-0.004) (+0.009)(-0.008), and the scalar spectral tilt, n(s) approximately 1.01(+0.09)(-0.07) (+0.17)(-0.14). These data are consistent with inflationary initial conditions for structure formation. Taken together with other cosmological observations, they imply the existence of both nonbaryonic dark matter and dark energy in the Universe.

Journal Article↗
PubMed2001

Ubiquitin dependent proteolysis is activated in apoptotic fibroblasts in culture.

The ubiquitin mediated pathway constitutes an early response in cultured cells where apoptosis, assessed by internucleosomal specific DNA fragmentation, was induced by serum withdrawal. Data demonstrate that nuclear ubiquitin proteolytic system, but not cytoplasmic, is activated. This activation is paralleled by a substantial chromatin de-condensation. We suggest that chromatin relaxation is causative of the fragmentation since it exposes the DNA to nucleolytic attack. Finally, maintenance of homeostasis and induction of apoptosis seem to undergo a parallel contemporary pathway with a possible mutual feedback.

Animals↗
PubMed2000

Measurement of a Peak in the Cosmic Microwave Background Power Spectrum from the North American Test Flight of Boomerang.

We describe a measurement of the angular power spectrum of anisotropies in the cosmic microwave background (CMB) at scales of 0&fdg;3 to 5 degrees from the North American test flight of the Boomerang experiment. Boomerang is a balloon-borne telescope with a bolometric receiver designed to map CMB anisotropies on a long-duration balloon flight. During a 6 hr test flight of a prototype system in 1997, we mapped more than 200 deg(2) at high Galactic latitudes in two bands centered at 90 and 150 GHz with a resolution of 26&arcmin; and 16&farcm;5 FWHM, respectively. Analysis of the maps gives a power spectrum with a peak at angular scales of 1 degrees with an amplitude 70 µK(CMB).

Journal Article↗
PubMed2000

A flat Universe from high-resolution maps of the cosmic microwave background radiation

The blackbody radiation left over from the Big Bang has been transformed by the expansion of the Universe into the nearly isotropic 2.73 K cosmic microwave background. Tiny inhomogeneities in the early Universe left their imprint on the microwave background in the form of small anisotropies in its temperature. These anisotropies contain information about basic cosmological parameters, particularly the total energy density and curvature of the Universe. Here we report the first images of resolved structure in the microwave background anisotropies over a significant part of the sky. Maps at four frequencies clearly distinguish the microwave background from foreground emission. We compute the angular power spectrum of the microwave background, and find a peak at Legendre multipole Ipeak = (197 +/- 6), with an amplitude delta T200 = (69 +/- 8) microK. This is consistent with that expected for cold dark matter models in a flat (euclidean) Universe, as favoured by standard inflationary models.

Journal Article↗
PubMed2000

The ionophore monensin inhibits mouse polyomavirus DNA replication and destabilizes viral early mRNAs.

Monensin is a ionophore compound with different biological activities. It raises the intralysosomal pH, it binds the plasma membranes particularly at the level of the cisternal system of the Golgi apparatus. It causes imbalance in the intramembrane ion traffic and inhibits export of secretory proteins at membrane level. Monensin blocks endocytosis and therefore impedes entry of toxic molecules. The drug also inhibits viral proliferation of RNA and DNA viruses such as vesicular stomatitis, influenza and human polyomaviruses. In this report we show that monensin effectively abolishes viral DNA replication of mouse polyomavirus. Results show that the half life of viral early mRNAs is significantly reduced in the presence of the drug. Therefore we suggest that the reduction of viral DNA synthesis is a consequence of the reduced intranuclear pool of viral early antigens.

Animals↗
PubMed1997

Apoptosis dependent decrease of the intramembrane ion traffic in cultured mouse fibroblasts shown by conductivity dispersion.

We have investigated the intramembranal ion traffic in apoptotic 3T6 cells in culture. Apoptosis was induced by various treatments, such as serum deprivation, high density growth and hydrogen peroxide at subnecrotic doses. Cell death was assessed by nucleosomal DNA fragmentation, single cell electrophoresis, immunofluorescence and histological staining. To study the modifications of membrane structure and function, we adopted a well established biophysical strategy based on the measurement of the electrical conductivity of cell suspensions, as a function of the frequency of the electrical field applied to the sample. A comparison between the conductivity of normal and apoptotic cell suspensions shows that programmed cell death causes a decrease of membrane conductivity which indicates a diminished intramembranal ion traffic. Our results strongly suggest that one of the early events in the triggering of apoptosis is represented by an overall reduction of plasma membrane function. Finally, our results are in agreement with the idea that the nucleus is not the sole target of the apoptotic process.

Animals↗
PubMed1996

Electrical conductivity dispersion as a probe of membrane modifications in mouse polyomavirus infected cells in culture.

In this report we investigate the inhibition of membrane conductivity, due to the murine polyomavirus infection in permissive cells in culture. We define experimental conditions to have reproducible results and demonstrate that the intensity of the effects on the cell membrane, depends upon the virus titer used in the infection. Finally, the virus dependent effects disappear if the infection is performed in the presence of a drug that inhibits polymavirus DNA replication.

Animals↗
PubMed1995

Role of mouse polyomavirus late region in the control of viral DNA replication: a review.

The genome of polyomaviruses is divided into two coding regions: the early and the late region. A relatively short regulatory sequence, encompassing the origin of viral DNA replication (ori), separates the two regions encoding the structural genes. In mouse polyomavirus (Py) in particular, the early DNA codes for three antigens: large, middle and small T-antigen (L-T, M-T and S-T, respectively). Large T antigen binds ori and thus regulates both viral DNA transcription and replication. Middle T antigen has been shown to mediate malignant transformation in non-permissive cells in vitro. No defined function has been assigned to the small T antigen although this gene product is thought to act synergistically both with L- and M-T antigens. The viral late region of Py encodes also three different genes whose products form the viral capsid during the productive infection cycle in permissive cells. Py early region was thought to be the only part of the genome necessary to code for proteins of functional and regulatory significance. The viral late region, on the other hand, was for a long time considered a simple reservoir of structural information, since it codes for capsid proteins and was supposedly devoid of functional control properties. This short review is focused on recent works from our and other laboratories, reporting evidence that in Py also the late region has a functional role since late sequences are involved in the control of viral DNA replication and in capsid assembly. Results indicating that this might be true for the cognate simian virus SV40 will be also reviewed.

Animals↗
PubMedDate not supplied

Variations of telomerase activity in cultured mouse fibroblasts upon proliferation of polyomavirus.

Telomerase plays a central role in various biological phenomena such as cell differentiation and proliferation, apoptosis, malignant transformation and virus infection, for instance HIV and papillomavirus. In addition, it has recently been shown that, in human fibroblasts transformed by monkey polyomavirus SV40, telomeres became stabilized as a consequence of telomerase activation. However, no information exists on the effects of acute infection by murine polyomavirus on the telomeres maintenance and telomerase activity in the host cell. In this paper we report on a differential activity of telomerase in productively infected cells. The results showed a decreased activity of the enzyme as assessed by the TRAP assay. The decrease had already occurred at a non-lytic time of infection and was observed both after infection and naked DNA transfection. Therefore nuclear decapsidation is not involved in the determination of the phenomenon that is attributed to the proliferation of the virus.

Animals↗
PubMedDate not supplied

The diimide drug PIPER has a cytotoxic dose-dependent effect in vitro and inhibits telomere elongation in HELA cells.

It is known that, in vitro, PIPER (N,N'-bis [2-(1-piperidino)ethyl]-3,4,9,10-tetracarboxylic diimide) induces the formation of the Hoogsteen quadruplex structure in telomere DNA, thus inhibiting the polymerisation of telomeric repeats. Since the action of PIPER in vivo has been scarcely investigated, this study was addressed to gain some insight into the effects of this drug on cultured HeLa cells. Vital staining with erythrosine, performed on cells exposed to different PIPER concentrations (from 1 to 50 microM), showed that the drug exerts a dose-dependent cytotoxic effect, clearly evident after a short-term (24 h) treatment. This early cytotoxic effect of PIPER on cultured HeLa cells was confirmed by a spectrophotometric/colorimetric method employing methylthiazoletetrazolium (Mossmann assay). Hematoxylin/eosin staining of cells treated with PIPER for 24 h showed a nuclear condensation and a cytoplasmic vacuolisation, very pronounced at higher drug concentrations. These pictures suggest that PIPER-induced cell death might be of the apoptotic type. Finally, the anti-telomerase activity of PIPER was monitored by TRAP assay, performed on HeLa cell nuclear extracts treated with increasing drug concentrations. It was found that some inhibition of telomerase is apparent even at low concentrations, while at the highest concentration the enzyme is completely inhibited. These results indicate that the cytotoxic power of PIPER is possibly related to its antitelomeric effect.

Dose-Response Relationship, Drug↗