Cystatin C (Cys C) is a cysteine protease inhibitor produced at a constant rate by nucleated cells, filtered through the glomerular membrane and reabsorbed by kidney tubular cells. Aim of this ...cross-sectional and longitudinal study was to assess serum Cys C and creatinine (Crea) concentrations in thyroid dysfunction. One hundred and eighty-one patients, 26 with untreated non-toxic nodular goiter, 58 with hyperthyroidism, 31 on L-T4 suppressive therapy for non-toxic nodular goiter, 35 with short-term hypothyroidism after L-T4 withdrawal to perform whole body scan for thyroid cancer, 11 with long-term hypothyroidism due to chronic autoimmune thyroiditis and 20 patients with mild hypothyroidism were enrolled in the study. Fifty-seven age- and sex-matched normal subjects served as controls. Serum Cys C, Crea, free T4 (FT4), FT3 and TSH were assessed. Thirty hyperthyroid patients and 35 short-term hypothyroid patients were followed prospectively until euthyroidism was reached by methimazole or L-T4 therapy. The cross-sectional study showed that mean serum Crea concentrations were significantly reduced in overt hyperthyroid or subclinical hyperthyroid patients, while it was increased in overt hypothyroid patients, but not in mild hypothyroidism. Conversely, serum Cys C levels were significantly increased in overt hyperthyroid patients compared to controls (p<0.05), and significantly decreased in short-term, long-term and mild hypothyroids (p<0.05, p<0.05, p<0.01, respectively). However, 36 (62%) hyperthyroid patients and 50 (76%) hypothyroid patients had normal serum Cys C values. In the prospective study, restoration of euthyroidism by either methimazole or L-T4 therapy was associated with normalization of mean serum Cys C concentrations. In conclusion, thyroid dysfunction affects serum Cys C concentration, possibly influencing the production rate of the protein. However, the observation that hyper- or hypothyroid patients have normal serum Cys C levels limits its use as a marker of peripheral thyroid hormone effect.
Obesity represents the single greatest ongoing roadblock to improving cardiovascular health. Prolonged obesity is associated with fundamental changes in the integrative control of energy balance, ...including the development of selective leptin resistance, which is thought to contribute to obesity-associated hypertension, and adaptation of resting metabolic rate (RMR) when excess weight is reduced. Leptin and the melanocortin system within the hypothalamus contribute to the control of both energy balance and blood pressure. While the development of drugs to stimulate RMR and thereby reverse obesity through activation of the melanocortin system has been pursued, most of the resulting compounds simultaneously cause hypertension. Evidence supports the concept that although feeding behaviors, RMR, and blood pressure are controlled through mechanisms that utilize similar molecular mediators, these mechanisms exist in anatomically dissociable networks. New evidence supports a major change in molecular signaling within AgRP (Agouti-related peptide) neurons of the arcuate nucleus of the hypothalamus during prolonged obesity and the existence of multiple distinct subtypes of AgRP neurons that individually contribute to control of feeding, RMR, or blood pressure. Finally, ongoing work by our laboratory and others support a unique role for AT
(angiotensin II type 1 receptor) within one specific subtype of AgRP neuron for the control of RMR. We propose that understanding the unique biology of the AT
-expressing, RMR-controlling subtype of AgRP neurons will help to resolve the selective dysfunctions in RMR control that develop during prolonged obesity and potentially point toward novel druggable antiobesity targets that will not simultaneously cause hypertension.
The present work focuses on the impact of anthropogenic multi-pollutants on modern concrete buildings exposed in two different European urban areas: Centennial Hall in Wroclaw (Poland) and Casa ...Galleria Vichi in Florence (Italy). Through a range of analytical techniques the complete characterization of the damage layer collected from the buildings under study has been achieved for the first time, including quantitative measurements of the carbon content. The experimental results allow the identification and prioritization of the air pollutants responsible for the surface deterioration, finding gypsum to be the main damage product on surfaces sheltered from rain runoff, with embedded particulate matter, especially carbonaceous particles, responsible for darkening of the building walls. The discrimination of carbon fractions shows different concentrations of elemental and organic carbon within the damage layers, depending on the location of the buildings. This step is essential for identifying the anthropogenic sources causing deterioration on the buildings, including the aesthetic impairment of surfaces. The contribution of air pollutants is also reflected by the elements found in the damage layers, while the evaluation of the enrichment factors is useful for identifying the elements of anthropogenic origin.
► The research focused on the impact of multi-pollutants on concrete buildings. ► SO
2 and particles emitted by combustion sources have priority in damage formation. ► Results show the correlation between building location and damage layer composition. ► Carbon fractions analyses was a key in finding pollutant sources causing damage. ► Elemental data processing allowed the identification of the origin of elements.
Bottom and fly ashes coming from the urban wastes incineration represent a by-product nowadays landfilled. By mixing different amount of these residues with others inert materials, such as glass ...cullet and feldspar waste, two vitrifiable mixtures are tailored. Glasses, obtained by means of vitrification process, are chemically stable with low leachability of contaminants and show comparable properties to those of commercial soda-lime glasses. Moreover, from the thermal and mechanical characterisation the tendency of these glasses to crystallise, for their transformation into glass-ceramic materials, has been evidenced.
A comparative evaluation of the corrosion behaviour of a G85 bronze in acid rain solutions was performed. As weathering technique, a wet–dry device was used to simulate a cyclic exposure to stagnant ...rain. The weathering solutions were a collected natural rain and an artificial solution reproducing the natural rain. The solutions were periodically monitored as concerns pH and metallic ion concentrations. On the aged specimens, surface studies were performed through OM, SEM and Raman analyses. At the end of weathering tests (40 days), weight loss measurements were carried out.
The aim of this work was to examine the reproducibility in laboratory of the corrosive conditions determined by a natural acid rain. The final goal of this research is to investigate the dissolution of a quaternary alloy exposed to acid rains.
The results showed slightly different corrosion behaviours as a consequence of the exposure to natural or synthetic rain. Concerning the mechanism of corrosion of G85 bronze, the innovative approach adopted in this study allowed one to point out the contribution of each alloying element to the general corrosion. Actually, while Cu and Pb progressively form insoluble corrosion compounds, Zn continuously dissolves, without forming detectable insoluble products. The absence of dissolved tin is remarkable.
Bird droppings are often quoted as a decay agent for outdoor goods, in particular buildings and statues. Undoubtedly, they represent one of the major causes of aesthetic damage on outdoor materials, ...but the real chemical damage they are able to induce, in particular on metals, is not so well studied. This work focused on the short term role of uric acid, the main constituent of bird urine, with respect to copper, which make such an important contribution to architectural elements of buildings and outdoor sculpture. Preliminary results of laboratory tests and analyses on real exposed samples showed that uric acid chemically affects copper and bronzes: the surface of the metal is modified and copper urates formed. Also natural patina, formed on statues and roof, react with uric acid, even if it seems to afford some protection toward bird droppings. In general, experimental results confirm that the potential chemical damage by bird droppings is significant when considering external cultural heritage such as statues, metal monuments and buildings with historic copper roofs.
Prolonged obesity is associated with blunted feeding and thermogenic autonomic responses to leptin, but cardiovascular responses to leptin are maintained. This state of selective leptin resistance ...is, therefore, proposed to contribute to the pathogenesis and maintenance of obesity-associated hypertension. Cells of the arcuate nucleus of the hypothalamus detect leptin, and although the cellular and molecular mechanisms remain unclear, altered arcuate nucleus biology is hypothesized to contribute to selective leptin resistance. Male C57BL/6J mice were fed a high-fat diet (HFD) or chow from 8 to 18 weeks of age, as this paradigm models selective leptin resistance. Nuclei were then isolated from arcuate nucleus for single-nucleus RNA sequencing. HFD caused expected gains in adiposity and circulating leptin. Twenty-three unique cell-type clusters were identified, and Ingenuity Pathway Analysis was used to explore changes in gene expression patterns due to chronic HFD within each cluster. Notably, gene expression signatures related to leptin signaling exhibited suppression predominantly in neurons identified as the Agouti-related peptide (Agrp) subtype. Ingenuity Pathway Analysis results were also consistent with alterations in CREB (cAMP response element-binding protein) signaling in Agrp neurons after HFD, and reduced phosphorylated CREB was confirmed in arcuate nucleus after prolonged HFD by capillary electrophoresis-based Western blotting. These findings support the concept that prolonged HFD-induced obesity is associated with selective changes in Agrp neuron biology, possibly secondary to altered CREB signaling.
Adaptation of resting metabolic rate (RMR) contributes to the maintenance of human obesity, yet RMR control and how this system changes during obesity remains poorly defined. Desensitization of the ...brain to leptin has been proposed to contribute. Leptin normally suppresses Agouti‐related peptide (AgRP) expression in the arcuate nucleus of the hypothalamus (ARC) to disinhibit (increase) melanocortin‐mediated RMR stimulation. Diet‐induced obesity (DIO) increases leptin, but paradoxically exaggerates Agrp expression and causes RMR adaptation. Thus, something connecting leptin to Agrp control becomes dysfunctional during DIO. Our previous data indicate that within the ARC, disruption in the extracellular signal‐regulated kinase (ERK) cascade occurs during DIO. ERK normally phosphorylates Krüppel‐like factor 4 (KLF4), inactivating it. As KLF4 binds to the AgRP promoter to increase transcription, its inactivation results in reduced Agrp expression. We hypothesize that this mechanism becomes dysfunctional within AgRP neurons during DIO, such that KLF4 binding to the AgRP promoter increases despite increased ERK activity.
Mouse hypothalamic GT1‐7 cells (model of AgRP neurons) were treated with leptin (1 uM, 15 min or 1 hr) and pERK/ERK ratio was measured by Simple WES and Agrp mRNA expression via qPCR, respectively. Leptin was given to chow‐fed adult mice (2 ug/g ip 30 min) and ARC pERK/ERK ratio was measured, as well as RMR assessed by respirometry. To examine consequences of ERK or KLF4 disruption upon cardiometabolic phenotypes, mice harboring a conditional version of endogenous Mapk1 or Klf4 were crossed with mice expressing Cre via the Agrp locus.
In GT1‐7 cells, leptin increased pERK/ERK ratio (1 uM, 15 min leptin n=3, +89% vs vehicle n=2, p<0.05) and suppressed Agrp expression (1 uM, 1 hr leptin n=2, ‐54.1% vs vehicle n=6, p<0.05). In chow‐fed adult mice, leptin injection caused an increase in the ARC pERK/ERK ratio (2 ug/g ip 30 min leptin n=11, +43.8% vs saline n=9, p<0.05). Additionally, leptin stimulated RMR in adult‐chow fed mice (1 ug/g ip leptin n=8, 16.5‐fold of vehicle n=8, p<0.05). DIO caused increases in endogenous plasma leptin and an increase in the ARC pERK/ERK ratio (High Fat Diet (HFD; n=5), +54.4% vs chow n=4, p<0.05), but ARC Agrp expression was not suppressed (HFD n=4, 1.62 fold of chow n=4, p<0.05). There was a possible exaggeration of weight gain in Agrp‐Cre+, Mapk1F/F mice compared to controls following HFD (KOs n=2, +16.8% vs controls n=3). In contrast, weight gain was possibly attenuated in Agrp‐Cre+, Klf4F/F mice compared to controls following HFD (KO n=1, ‐10.7% vs controls n=2). RMR was higher in chow‐fed Agrp‐Cre+, Klf4F/F mice compared to controls (KOs n=5 +8.3% vs controls n=7, p<0.05) and may be exaggerated following HFD (KO n=1 +13.0% vs controls n=3). Together, these findings suggest that ERK and KLF4 within AgRP neurons appear to contribute to the control of AgRP and thus RMR. These findings may identify ERK control of KLF4 and KLF4 as a potential therapeutic target to maintain/restore RMR control after prolonged obesity.
Purpose of Review
Here, we review the current understanding of the functional neuroanatomy of neurons expressing Agouti-related peptide (AgRP) and the angiotensin 1A receptor (AT
1A
) within the ...arcuate nucleus (ARC) in the control of energy balance.
Recent Findings
The development and maintenance of obesity involves suppression of resting metabolic rate (RMR). RMR control is integrated via AgRP and proopiomelanocortin neurons within the ARC. Their projections to other hypothalamic and extrahypothalamic nuclei contribute to RMR control, though relatively little is known about the contributions of individual projections and the neurotransmitters involved. Recent studies highlight a role for AT
1A
, localized to AgRP neurons, but the specific function of AT
1A
within these cells remains unclear.
Summary
AT
1A
functions within AgRP neurons to control RMR, but additional work is required to clarify its role within subpopulations of AgRP neurons projecting to distinct second-order nuclei, and the molecular mediators of its signaling within these cells.
In favourable conditions of low temperature and low oxygen concentration, archaeological waterlogged wooden artefacts, such as shipwrecks, can survive with a good state of preservation. Nevertheless, ...anaerobic bacteria can considerably degrade waterlogged wooden objects with a significant loss in polysaccharidic components. Due to these decay processes, wood porosity and water content increase under ageing. In such conditions, the conservation treatments of archaeological wooden artefacts often involve the replacement of water with substances which fill the cavities and help to prevent collapse and stress during drying. The treatments are very often expensive and technically difficult, and their effectiveness very much depends on the chemical and physical characteristics of the substances used for impregnation. Also important are the degree of cavity-filling, penetration depth and distribution in the structure of the wood. In this study, the distribution in wood cavities of some mixtures based on polyethylene glycols and colophony, used for the conservation of waterlogged archaeological wood, was investigated using synchrotron radiation X-ray computed microtomography (SR-µCT). This non-destructive imaging technique was useful for the study of the degraded waterlogged wood and enabled us to visualise the morphology of the wood and the distribution of the materials used in the wood treatments. The study has shown how deposition is strictly related to the dimension of the wooden cavities. The work is currently proceeding with the comparison of synchrotron observations with the data of the solutions viscosity and with those of the properties imparted to the wood by the treatments.
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