Q-Elastography in the Presurgical Diagnosis of Thyroid Nodules with Indeterminate Cytology

Quantitative ultrasound (US) elastography (Q-USE), able to evaluate tissue stiffness has been indicated as a new diagnostic tool to differentiate benign from malignant thyroid lesions. Aim of this prospective study, conducted at the Department of Surgical Sciences, of the “Sapienza” University of Rome, was to evaluate the diagnostic accuracy of Q-USE, compared with US parameters, in thyroid nodules with indeterminate cytology (Thy3).The case study included 140 nodules from 140 consecutive patients. Patient’s thyroid nodules were evaluated by Q-USE, measuring the strain ratio (SR) of stiffness between nodular and surrounding normal thyroid tissue, and conventional US parameters prior fine-needle aspiration cytology. Those with Thy3 diagnosis were included in the study. Forty of the nodules analyzed harbored a malignant lesion. Q-USE demonstrated that malignant nodules have a significant higher stiffness with respect to benign one and an optimun SR cut-off value of 2.05 was individuated following ROC analysis. Univariate analysis showed that hypoechogenicity, irregular margins and SR >2.05 associated with malignancy, with an accuracy of 67.2%, 81,0% and 89.8%, respectively. Data were unaffected by nodule size or thyroiditis. These findings were confirmed in multivariate analysis demonstrating a significant association of the SR and the irregular margins with thyroid nodule’s malignancy. In conclusion, we demonstrated the diagnostic utility of Q-USE in the differential diagnosis of thyroid nodules with indeterminate cytology that, if confirmed, could be of major clinical utility in patients’ presurgical selection.     

Effect of methodological and ecological approaches on heterogeneity of nest-site selection of a long-lived vulture

The application of scientific-based conservation measures requires that sampling methodologies in studies modelling similar ecological aspects produce comparable results making easier their interpretation. We aimed to show how the choice of different methodological and ecological approaches can affect conclusions in nest-site selection studies along different Palearctic meta-populations of an indicator species. First, a multivariate analysis of the variables affecting nest-site selection in a breeding colony of cinereous vulture (Aegypius monachus) in central Spain was performed. Then, a meta-analysis was applied to establish how methodological and habitat-type factors determine differences and similarities in the results obtained by previous studies that have modelled the forest breeding habitat of the species. Our results revealed patterns in nesting-habitat modelling by the cinereous vulture throughout its whole range: steep and south-facing slopes, great cover of large trees and distance to human activities were generally selected. The ratio and situation of the studied plots (nests/random), the use of plots vs. polygons as sampling units and the number of years of data set determined the variability explained by the model. Moreover, a greater size of the breeding colony implied that ecological and geomorphological variables at landscape level were more influential. Additionally, human activities affected in greater proportion to colonies situated in Mediterranean forests. For the first time, a meta-analysis regarding the factors determining nest-site selection heterogeneity for a single species at broad scale was achieved. It is essential to homogenize and coordinate experimental design in modelling the selection of species' ecological requirements in order to avoid that differences in results among studies would be due to methodological heterogeneity. This would optimize best conservation and management practices for habitats and species in a global context.     

Circadian-related heteromerization of adrenergic and dopamine D₄ receptors modulates melatonin synthesis and release in the pineal gland

The role of the pineal gland is to translate the rhythmic cycles of night and day encoded by the retina into hormonal signals that are transmitted to the rest of the neuronal system in the form of serotonin and melatonin synthesis and release. Here we describe that the production of both melatonin and serotonin by the pineal gland is regulated by a circadian-related heteromerization of adrenergic and dopamine D₄ receptors. Through α_{1 B}-D₄ and β₁-D₄ receptor heteromers dopamine inhibits adrenergic receptor signaling and blocks the synthesis of melatonin induced by adrenergic receptor ligands. This inhibition was not observed at hours of the day when D₄ was not expressed. These data provide a new perspective on dopamine function and constitute the first example of a circadian-controlled receptor heteromer. The unanticipated heteromerization between adrenergic and dopamine D₄ receptors provides a feedback mechanism for the neuronal hormone system in the form of dopamine to control circadian inputs.     

Mitochondrial respiratory thresholds regulate yeast chronological life span and its extension by caloric restriction

We have explored the role of mitochondrial function in aging by genetically and pharmacologically modifying yeast cellular respiration production during the exponential and/or stationary growth phases and determining how this affects chronological life span (CLS). Our results demonstrate that respiration is essential during both growth phases for standard CLS, but that yeast have a large respiratory capacity, and only deficiencies below a threshold (~40% of wild-type) significantly curtail CLS. Extension of CLS by caloric restriction also required respiration above a similar threshold during exponential growth and completely alleviated the need for respiration in the stationary phase. Finally, we show that supplementation of media with 1% trehalose, a storage carbohydrate, restores wild-type CLS to respiratory-null cells. We conclude that mitochondrial respiratory thresholds regulate yeast CLS and its extension by caloric restriction by increasing stress resistance, an important component of which is the optimal accumulation and mobilization of nutrient stores.     

Plant extracellular ATP signalling: new insight from proteomics

Complex signalling systems have evolved in multicellular organisms to enable cell-to-cell communication during growth and development. In plants, cell communication via the extracellular matrix (apoplast) controls many processes vital for plant survival. Secretion of ATP into the extracellular matrix is now recognised as a previously unknown stimulus for cell signalling with a role in many aspects of plant physiology. In the last decade, the secondary messenger molecules in extracellular ATP signalling were identified, but the downstream gene and protein networks that underpin plant responses to extracellular ATP are only beginning to be characterised. Here we review the current status of our knowledge of plant extracellular signalling and demonstrate how applying state-of-the art proteomic technologies is rapidly bringing new discoveries in extracellular ATP research. We discuss how monitoring of the global proteomic profile during responses to modulation of extracellular ATP signalling has led to novel insight into pathogen defence systems and plant programmed cell death regulation. On the basis of extensive proteomic, pharmacological, and reverse genetics data, extracellular ATP has been confirmed to constitute an important molecular switch that tightly controls organellar energy metabolism, reprogramming of primary metabolic pathways, and redirection of resources to protein networks that support adaptation of plants to stress.     

Embryology at the Universities of Lwow and Wroclaw

Embryological research at the University of Wroclaw covers hormonal control of metamorphosis, primarily invertebrate embryology and gametogenesis, vertebrate myogenesis and the developmental impact of external factors. Developmental studies at the University of Wroclaw are a continuation of those conducted at the former Jan Kazimierz (Johannes Casimirus) University in Lwow before World War II. The Wroclaw embryological school is best characterized as comparative embryology which approaches embryonic development experimentally as well as through the analysis of its natural diversity.     

The Socioeconomic Impact of Truffle Cultivation in Rural Spain<Superscript>1</Superscript>

The Socioeconomic Impact of Truffle Cultivation in Rural Spain. Commercial black truffle (Tuber melanosporum) plantations have been promoted in Europe with the intention of benefiting rural economies while conserving biodiversity through the expansion of oak woodlands. In this context, a socioeconomic study was conducted around the town of Sarrión in eastern Spain, where government subsidies have supported oak reforestation and truffle cultivation in unproductive hilly areas since 1987. Currently there are about 4,500 ha of truffle orchards in the surrounding county and 530 members in the local truffle association, which has provided a key forum for truffle cultivators to share technical, financial and administrative experiences. Structured interviews were carried out in 2002 with a number of orchard owners, as well as representatives of financial and governmental institutions. Truffles, which are harvested using trained dogs, typically fetch local cultivators average prices of 220–670 EUR/kg, although retail prices of high-quality specimens may reach twice this amount. In addition to the direct economic impact, an increase in local land prices was also documented, as well as a tendency for continued expansion of truffle orchards, and thus oak reforestation. In conclusion, the promotion of truffle cultivation through autonomous community and provincial government subsidies, in conjunction with support by local banks, a dedicated local truffle association, and growing interest on behalf of local farmers, seems to have achieved the mutual goals of biodiversity conservation and improving the rural economy in this region of Spain.     

Dex-ras1 and Serum- and Glucocorticoid-inducible Protein Kinase 1: Regulation of Expression by Dexamethasone in HEK293 Cells

The molecular and cellular basis of the psychotropic actions of adrenal corticosteroids is poorly understood. Previously, we reported that modulation of large conductance Ca²⁺-activated potassium channel (BK-channel) function by glucocorticoids can be recapitulated in human embryonic kidney293 (HEK293) cells (J Physiol 537:57, 2001). In the present paper, we examined the effect of dexamethasone on the expression of candidate mediator proteins of glucocorticoid action, dex-ras1 and serum and glucocorticoid inducible protein kinase 1 (SGK), in HEK293 cells. Dex-ras1 mRNA was readily detectable under basal conditions however, no changes of dex-ras1 mRNA expression occurred upon exposure to 100 nM of dexamethasone for 2 h. In contrast, a 2.5-fold increase of SGK mRNA was found under similar conditions. Total levels of cellular SGK protein were unaltered upon exposure to dexamethasone, but a marked increase of SGK in a Triton-X100 insoluble fraction was observed. BK-channel α-subunits could not be co-immunoprecipitated with SGK. In summary, SGK, but not dex-ras1, mRNA is rapidly induced by glucocorticoid stimulation in HEK293 cells. However, there appears to be no direct protein-protein interaction between SGK and BK-channel α-subunits. Presented to mark the 70th birthday of Professor George Fink. Special issue article in honor of George Fink.     

Mutations in foregut SOX2+ cells induce efficient proliferation via CXCR2 pathway

Identification of the precise molecular pathways involved in oncogene-induced transformation may help us gain a better understanding of tumor initiation and promotion. Here, we demonstrate that SOX2⁺ foregut epithelial cells are prone to oncogenic transformation upon mutagenic insults, such as Kras^G12D and p53 deletion. GFP-based lineage-tracing experiments indicate that SOX2⁺ cells are the cells-of-origin of esophagus and stomach hyperplasia. Our observations indicate distinct roles for oncogenic KRAS mutation and P53 deletion. p53 homozygous deletion is required for the acquisition of an invasive potential, and Kras^G12D expression, but not p53 deletion, suffices for tumor formation. Global gene expression analysis reveals secreting factors upregulated in the hyperplasia induced by oncogenic KRAS and highlights a crucial role for the CXCR2 pathway in driving hyperplasia. Collectively, the array of genetic models presented here demonstrate that stratified epithelial cells are susceptible to oncogenic insults, which may lead to a better understanding of tumor initiation and aid in the design of new cancer therapeutics.     

Ecology of cavernicolous ciliates from the anchihaline lagoons of Mallorca

On the island of Mallorca, anchihaline lagoons, meromictic in character, are common in the flooded coastal karst. These subterranean lagoons, containing important populations of crustacea, maintain a connection, albeit tenuous, to the sea. Thus, the first truly quantitative study of marine ciliates inhabiting anchihaline lagoons was undertaken between April 1996 and April 1997. Physical and chemical measurements were taken in-situ, together with water samples for faunal analysis in each of four stratified lakes. These lagoons typically displayed a temperature inversion, an increase in conductivity and a decrease in dissolved oxygen concentration with depth. Ciliates were present in all lagoons studied, with a total of nine species recorded. All were assigned to known taxa. Spatial distribution of the trophic cells was noteworthy with populations clearly stratified within the water column, most being found at the waters surface, sometimes in association with rafts of floating calcite crystals, or in the sediment. Only on one occasion were ciliates recorded in mid-water. Abundance was very low, typically <1 ciliate cm^–3. The floating calcite crystals may form a delimitable biotope for ciliate populations. The role of the cyst in maintaining populations of ciliates in these cave waters is discussed.