PCOS is a common and heterogeneous endocrine disorder in women of reproductive age, frequently associated with metabolic abnormalities. It was estimated that about 75% of these subjects have an ...impairment of insulin action, as measured by gold standard methods. While the relationship between insulin resistance and PCOS is consistently shown by a number of studies, the mechanisms underlying its primary origin still remains an unsolved issue. Insulin resistance and the associated hyperinsulinemia can induce both the endocrine and reproductive traits of PCOS. However, androgen excess, in turn, can impair insulin action, directly and/or through several changes occurring in different tissues. Body fat excess, which is another common feature in these women, can contribute to worsening the whole picture. Nevertheless, insulin resistance may also be found in many normal-weight individuals. Endocrine and metabolic abnormalities can develop in different moments, and probably there is fetal programming of these alterations. However, a number of vicious circles, with bidirectional relationships between androgen excess and insulin resistance, and with the contribution of several other factors, make it extremely difficult to understand where this process really originates. This review summarizes available evidence on this topic, in order to better understand the complex relationships linking hyperandrogenism and impaired insulin action in women with PCOS.
The tropomyosin receptor kinase (TRK) family of receptor tyrosine kinases are encoded by NTRK genes and have a role in the development and normal functioning of the nervous system. Since the ...discovery of an oncogenic NTRK gene fusion in colorectal cancer in 1986, over 80 different fusion partner genes have been identified in a wide array of adult and paediatric tumours, providing actionable targets for targeted therapy. This review describes the normal function and physiology of TRK receptors and the biology behind NTRK gene fusions and how they act as oncogenic drivers in cancer. Finally, an overview of the incidence and prevalence of NTRK gene fusions in various types of cancers is discussed.
A new, mild, metal-free, HSiCl3-mediated reduction of both aromatic and aliphatic nitro groups to amines that is of wide general applicability, tolerant of many functional groups, and respectful of ...the stereochemical integrity of stereocenters is reported.
Innate immune responses to infection Tosi, Michael F.
Journal of Allergy and Clinical Immunology,
08/2005, Letnik:
116, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The human host survives many infectious challenges in the absence of preexisting specific (adaptive) immunity because of the existence of a separate set of protective mechanisms that do not depend on ...specific antigenic recognition. These antigen-independent mechanisms constitute innate immunity. Antimicrobial peptides are released at epithelial surfaces and disrupt the membranes of many microbial pathogens. Toll-like receptors on epithelial cells and leukocytes recognize a range of microbial molecular patterns and generate intracellular signals for activation of a range of host responses. Cytokines released from leukocytes and other cells exhibit a vast array of regulatory functions in both adaptive and innate immunity. Chemokines released from infected tissues recruit diverse populations of leukocytes that express distinct chemokine receptors. Natural killer cells recognize and bind virus-infected host cells and tumor cells and induce their apoptosis. Complement, through the alternative and mannose-binding lectin pathways, mediates antibody-independent opsonization, phagocyte recruitment, and microbial lysis. Phagocytes migrate from the microcirculation into infected tissue and ingest and kill invading microbes. These innate immune mechanisms and their interactions in defense against infection provide the host with the time needed to mobilize the more slowly developing mechanisms of adaptive immunity, which might protect against subsequent challenges.
Organic compounds occur in some chondritic meteorites, and their signatures on solar system bodies have been sought for decades. Spectral signatures of organics have not been unambiguously identified ...on the surfaces of asteroids, whereas they have been detected on cometary nuclei. Data returned by the Visible and InfraRed Mapping Spectrometer on board the Dawn spacecraft show a clear detection of an organic absorption feature at 3.4 micrometers on dwarf planet Ceres. This signature is characteristic of aliphatic organic matter and is mainly localized on a broad region of ~1000 square kilometers close to the ~50-kilometer Ernutet crater. The combined presence on Ceres of ammonia-bearing hydrated minerals, water ice, carbonates, salts, and organic material indicates a very complex chemical environment, suggesting favorable environments to prebiotic chemistry.
The physical properties of cometary nuclei observed today relate to their complex history and help to constrain their formation and evolution. In this article, we review some of the main physical ...properties of cometary nuclei and focus in particular on the thermal, mechanical, structural and dielectric properties, emphasising the progress made during the Rosetta mission. Comets have a low density of
480
±
220
kg
m
−
3
and a low permittivity of 1.9–2.0, consistent with a high porosity of 70–80%, are weak with a very low global tensile strength
<
100
Pa, and have a low bulk thermal inertia of
0
–
60
J
K
−
1
m
−
2
s
−
1
/
2
that allowed them to preserve highly volatiles species (e.g. CO, CO
2
, CH
4
, N
2
) into their interior since their formation. As revealed by 67P/Churyumov-Gerasimenko, the above physical properties vary across the nucleus, spatially at its surface but also with depth. The broad picture is that the bulk of the nucleus consists of a weakly bonded, rather homogeneous material that preserved primordial properties under a thin shell of processed material, and possibly covered by a granular material; this cover might in places reach a thickness of several meters. The properties of the top layer (the first meter) are not representative of that of the bulk nucleus. More globally, strong nucleus heterogeneities at a scale of a few meters are ruled out on 67P’s small lobe.
The mineralogy of Vesta, based on data obtained by the Dawn spacecraft's visible and infrared spectrometer, is consistent with howardite-eucrite-diogenite meteorites. There are considerable regional ...and local variations across the asteroid: Spectrally distinct regions include the south-polar Rheasilvia basin, which displays a higher diogenitic component, and equatorial regions, which show a higher eucritic component. The lithologic distribution indicates a deeper diogenitic crust, exposed after excavation by the impact that formed Rheasilvia, and an upper eucritic crust. Evidence for mineralogical stratigraphic layering is observed on crater walls and in ejecta. This is broadly consistent with magma-ocean models, but spectral variability highlights local variations, which suggests that the crust can be a complex assemblage of eucritic basalts and pyroxene cumulates. Overall, Vesta mineralogy indicates a complex magmatic evolution that led to a differentiated crust and mantle.
The typically dark surface of the dwarf planet Ceres is punctuated by areas of much higher albedo, most prominently in the Occator crater. These small bright areas have been tentatively interpreted ...as containing a large amount of hydrated magnesium sulfate, in contrast to the average surface, which is a mixture of low-albedo materials and magnesium phyllosilicates, ammoniated phyllosilicates and carbonates. Here we report high spatial and spectral resolution near-infrared observations of the bright areas in the Occator crater on Ceres. Spectra of these bright areas are consistent with a large amount of sodium carbonate, constituting the most concentrated known extraterrestrial occurrence of carbonate on kilometre-wide scales in the Solar System. The carbonates are mixed with a dark component and small amounts of phyllosilicates, as well as ammonium carbonate or ammonium chloride. Some of these compounds have also been detected in the plume of Saturn’s sixth-largest moon Enceladus. The compounds are endogenous and we propose that they are the solid residue of crystallization of brines and entrained altered solids that reached the surface from below. The heat source may have been transient (triggered by impact heating). Alternatively, internal temperatures may be above the eutectic temperature of subsurface brines, in which case fluids may exist at depth on Ceres today.
Studies of the dwarf planet (1) Ceres using ground-based and orbiting telescopes have concluded that its closest meteoritic analogues are the volatile-rich CI and CM carbonaceous chondrites. Water in ...clay minerals, ammoniated phyllosilicates, or a mixture of Mg(OH)2 (brucite), Mg2CO3 and iron-rich serpentine have all been proposed to exist on the surface. In particular, brucite has been suggested from analysis of the mid-infrared spectrum of Ceres. But the lack of spectral data across telluric absorption bands in the wavelength region 2.5 to 2.9 micrometres--where the OH stretching vibration and the H2O bending overtone are found--has precluded definitive identifications. In addition, water vapour around Ceres has recently been reported, possibly originating from localized sources. Here we report spectra of Ceres from 0.4 to 5 micrometres acquired at distances from ~82,000 to 4,300 kilometres from the surface. Our measurements indicate widespread ammoniated phyllosilicates across the surface, but no detectable water ice. Ammonia, accreted either as organic matter or as ice, may have reacted with phyllosilicates on Ceres during differentiation. This suggests that material from the outer Solar System was incorporated into Ceres, either during its formation at great heliocentric distance or by incorporation of material transported into the main asteroid belt.
The Visible and Infrared Spectrometer (VIR) instrument on the Dawn mission observed Ceres’s surface at different spatial resolutions, revealing a nearly uniform global distribution of surface ...mineralogy. Clearly, Ceres experienced extensive water‐related processes and chemical differentiation. The surface is mainly composed of a dark component (carbon, magnetite?), Mg‐phyllosilicates, ammoniated clays, carbonates, and salts. The observed species suggest endogenous, global‐scale aqueous alteration. While mostly uniform at regional scale, Ceres’s surface shows small localized areas with different species and/or variations in abundances. Few local exposures of water ice are seen, especially at higher latitudes. Sodium carbonates have been identified in several areas on the surface, notably in Occator bright faculae. Organic matter has also been discovered in several places, most conspicuously in a large area close to the Ernutet crater. The observed mineralogies, with the presence of ammoniated species and sodium salts, have a strong resemblance to materials found on other bodies of the outer solar system, such as Enceladus. This poses some questions about the original material from which Ceres accreted, suggesting a colder environment for such material with respect to Ceres’s present position.
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