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In this paper we discuss two different existing algorithms for computing topological entropy and we implement one of them in order to compute the isentropes for cubic polynomials.

Background Wearable monitoring devices based on inertial sensors have the potential to be used as a quantitative method in clinical practice for continuous assessment of gait disabilities in Parkinson’s disease (PD). Methods This manuscript introduces a new gait monitoring system adapted to patients with PD, based on a wearable monitoring device. To eliminate inter- and intra-subject variability, the computational method was based on heuristic rules with adaptive thresholds and ranges and a motion compensation strategy. The experimental trials involved repeated measurements of walking trials from two cross-sectional studies: the first study was performed in order to validate the effectiveness of the system against a robust 3D motion analysis with 10 healthy subjects; and the second-one aimed to validate our approach against a well-studied wearable IMU-based system on a hospital environment with 20 patients with PD. Results The proposed system proved to be efficient (Experiment I: sensitivity = 95,09% and accuracy = 93,64%; Experiment II: sensitivity = 99,53% and accuracy = 97,42%), time-effective (Experiment I: earlies = 13,71 ms and delays = 12,91 ms; Experiment II: earlies = 12,94 ms and delays = 12,71 ms), user and user-motion adaptable and a low computational-load strategy for real-time gait events detection. Further, it was measured the percentage of absolute error classified with a good acceptability (Experiment I: 3,02 ≤ e%≤12,94; Experiment II: 2,81 ≤ e%≤13,45). Lastly, regarding the measured gait parameters, it was observed a reflection of the typical levels of motor impairment for the different disease stages. Conclusion The achieved outcomes enabled to verify that the proposed system can be suitable for gait analysis in the assistance and rehabilitation fields.

Coupled oscillator models where N oscillators are identical and symmetrically coupled to all others with full permutation symmetry S N are found in a variety of applications. Much, but not all, work on phase descriptions of such systems consider the special case of pairwise coupling between oscillators. In this paper, we show this is restrictive—and we characterize generic multi-way interactions between oscillators that are typically present, except at the very lowest order near a Hopf bifurcation where the oscillations emerge. We examine a network of identical weakly coupled dynamical systems that are close to a supercritical Hopf bifurcation by considering two parameters, ϵ (the strength of coupling) and λ (an unfolding parameter for the Hopf bifurcation). For small enough λ > 0 there is an attractor that is the product of N stable limit cycles; this persists as a normally hyperbolic invariant torus for sufficiently small ϵ > 0 . Using equivariant normal form theory, we derive a generic normal form for a system of coupled phase oscillators with S N symmetry. For fixed N and taking the limit 0 ϵ ≪ λ ≪ 1 , we show that the attracting dynamics of the system on the torus can be well approximated by a coupled phase oscillator system that, to lowest order, is the well-known Kuramoto–Sakaguchi system of coupled oscillators. The next order of approximation generically includes terms with up to four interacting phases, regardless of N . Using a normalization that maintains nontrivial interactions in the limit N → ∞ , we show that the additional terms can lead to new phenomena in terms of coexistence of two-cluster states with the same phase difference but different cluster size.

International audience; The impact of high hydrostatic pressure (HHP) treatments on the phenolic compounds composition of a red wine was studied after storage in order to evaluate the potential of this technology as an enological practice. Red wines pressurized at 500 and 600 MPa at 20 °C for 5 and 20 min, respectively, showed a lower content of monomeric anthocyanins (13 to 14%), phenolic acids (8 to 11%), and flavonols (14 to 19%) after 5 months of storage, when compared to the unpressurized wine. These results, together with the different degree of tannin polymerization and flavan-3-ol content in the pressurized wines led to propose an effect of HHP in the increase of polymerization and cleavage reactions of proanthocyanidins. The sensorial analysis of pressurized wines showed lower astringency, a higher intensity of cooked fruit aroma and lower intensity of fruity notes, when compared with the unpressurized wine. These effects are associated to those observed during wine aging. Industrial relevance During the last decade, the use of high hydrostatic pressure (HHP) as a non-thermal technology for food preservation and modification has increased substantially. Recently, pressure treatments have shown to influence long term red wine physicochemical and sensorial characteristics, leading to aged wine-like characteristics. Therefore, the use of HHP technology to modify wine composition could benefit the wine industry, especially to improve wines with low aging potential. This work shows that HHP can be potentially used as enological practice, modulating the organoleptic properties of wine by decreasing astringency and increasing pleasant aromas. It seems possible to exploit commercially the production of young red wines with distinct characteristics using this technology, addressing the market and consumer demand.

Leishmaniosis caused by Leishmania infantum is a zoonotic disease endemic in many countries of America, Asia and Europe, including Portugal. Dogs are the major reservoir of L. infantum, but domestic cats may also be infected. Three clinical cases of feline leishmaniosis are described, with ocular clinical signs as the only manifestation of the disease. A case had bilateral anterior uveitis and a granulomatous conjunctivitis, another one presented keratitis and the third case had a nodular blepharitis. All the affected cats had high serum titres of antibodies to L. infantum, while polymerase chain reaction results were positive in two of the cats. Although all cats in the present study improved after treatment with meglumine antimoniate and/or allopurinol, one of them died 6months later apparently due to a systemic L. infantum infection. The prevalence of disease may be underestimated in cats, because leishmaniosis is often not considered in the differential diagnosis of feline diseases. Feline leishmaniosis should be suspected in cats with ocular clinical signs and in those living in or traveling to areas where the zoonosis is endemic.

The impact of high hydrostatic pressure (HHP) treatments on volatile composition of sulphur dioxide-free wines during bottle storage was studied. For this purpose, white and red wines were produced without sulphur dioxide (SO2) and, at the end of the alcoholic fermentation, the wines were pressurised at 500 MPa and 425 MPa for 5 min. Wine with 40 ppm of SO2 and a wine without a preservation treatment were used as controls. More than 160 volatile compounds, distributed over 12 chemical groups, were identified in the wines by an advanced gas chromatography technique. The pressurised wines contained a higher content of furans, aldehydes, ketones, and acetals, compared with unpressurised wines after 9 months of storage. The changes in the volatile composition indicate that HHP treatments accelerated the Maillard reaction, and alcohol and fatty acid oxidation, leading to wines with a volatile composition similar to those of faster aged and/or thermally treated wines.

Nonsurgical sterilization methods are considered alternative tools for the worldwide challenge represented by canine overpopulation control. Intratesticular injection of zinc gluconate associated with DMSO arises as an option because of the effortless diffusion throughout the testicular parenchyma. This study aimed to verify the effectiveness of a double testicular injection of zinc gluconate associated with DMSO as a chemical contraceptive for male dogs. The study was conducted with 22 dogs treated with two intratesticular injections of the chemical solution (treated group; n = 15) or 0.9% NaCl solution (control group; n = 7) on a monthly interval. All animals were submitted to clinical examination, breeding soundness evaluation including morphologic and sonographic examination of the testes, assessment of libido, volume of the sperm-rich fraction, sperm motility, total sperm count, plasma membrane integrity, sperm morphologic abnormalities, and the total number of morphologically normal and motile sperm in the ejaculate. Blood samples were collected for serum testosterone analysis, and testicular tissue was morphologically and histologically evaluated. No clinical alterations and signs of pain or local sensitivity along the experimental period were noticed. However, the injection of zinc gluconate and DMSO significantly reduced libido and testosterone concentrations (even beyond the reference range for intact male dogs). Impairment of sperm quality-related variables was observed 15 days after the first intratesticular administration of zinc gluconate and DMSO (i.e., decrease in sperm count and sperm motility and an increase in major sperm defects and by this a decrease in the total number of morphologically normal and motile sperm). Testicular ultrasonographic analysis revealed reduction of testicular volume and changes of testicular echotexture in treated animals, compatible with tissue degeneration, fibrosis, and calcification of testicular parenchyma on histologic examination. In conclusion, intratesticular administration of zinc gluconate associated with DMSO reduces reproductive potential which may lead to subfertility or infertility in dogs.

Agraïments: The research of AR is supported by the Swedish Research Council (VR Grant 2010/5905). The authors would like to thank the Göran Gustafsson Foundation UU/KTH for financial support. We study the periodic solutions of the following kind of non-autonomous Duffing differential equation y + ay − εy 3 = εh(t, y, y), with a > 0, ε a small parameter and h a C 2 function in its variables.

Thirteen pyrrolidine-based iminosugar derivatives have been synthesized and evaluated for inhibition of α-glucosidase from rat intestine. The compounds studied were the non-hydroxy, mono-hydroxy and dihydroxypyrrolidines. All the compounds were N -benzylated apart from one. Four of the compounds had a carbonyl group in the 2,5-position of the pyrrolidine ring. The most promising iminosugar was the trans -3,4-dihydroxypyrrolidine 5 giving an IC 50 of 2.97 ± 0.046 and a K I of 1.18 mM. Kinetic studies showed that the inhibition was of the mixed type, but predominantly competitive for all the compounds tested. Toxicological assay results showed that the compounds have low toxicity. Docking studies showed that all the compounds occupy the same region as the DNJ inhibitor on the enzyme binding site with the most active compounds establishing similar interactions with key residues. Our studies suggest that a rotation of ∼90° of some compounds inside the binding pocket is responsible for the complete loss of inhibitory activity. Despite the fact that activity was found only in the mM range, these compounds have served as simple molecular tools for probing the structural features of the enzyme, so that inhibition can be improved in further studies.

The application of high hydrostatic pressure (HHP) in winemaking for substitution of the use of sulphurdioxide is still at a very early stage of development, since knowledge about the effect on physicochemicaland sensorial characteristics of the wine during storage is very scarce. In this work, the evolution of col-our, antioxidant activity and total phenolic compounds of SO 2 -free red wines treated by HHP and aged inbottles was followed for 12 months. The pressurised wines were compared with wine samples preparedwith addition of 40 ppm of SO 2 and without any of these two treatments. After 12 months, the pressur-ised wines presented higher values of CIELab parameters (a ⁄ , b ⁄ , and L ⁄ ) and a lower monomeric antho-cyanin content (45–61%) when compared to the unpressurised ones. The pressurised wines showed also abetter global sensorial assessment, with the pressure treatments imparting aged-like characteristics tothe wines. The wine deposits of pressurised wines had higher total phenolic content, namely proantho-cyanidins (3- to 10-fold). The results demonstrate that HHP can influence long term red wine physico-chemical and sensorial characteristics, hypothesised to be due to an increase of condensation reactionsof phenolic compounds, forming compounds with higher degree of polymerisation that became insolublein wine along storage. 2013 Elsevier Ltd. All rights reserved.

The impact of high hydrostatic pressure (HHP) treatments on physicochemical characteristics of sulphur dioxide-free white wines was studied during one year of bottle storage. For this purpose, a white wine was produced without the addition of sulphur dioxide (SO 2 ) and was pressurized at two pressure conditions, 500 and 425 MPa, for 5 min at 20 °C. A wine with 40 ppm of SO 2 and a wine with no preservation treatment were used as controls. Pressurized wines showed, after one year of storage, a more brownish color (higher a * and b * values and lower L *) and a slightly lower antioxidant activity and total content of phenolic compounds compared to the unpressurized wines (wine with SO 2 and wine without any treatment). These results, together with the lower content of free amino acids ( e.g. 87% less of serine) and higher content of furans ( e.g. 10 fold higher of 2-furfural), presented in the pressurized wines after nine months of storage, lead to propose an effect of HHP treatments in the acceleration of Maillard reactions occurring during the wine storage period. Industrial relevance HHP might be used in winemaking as an alternative process for preservation of wine, which can lead to the production of a wine with reduced amounts of SO 2 . Until now, the physicochemical and sensorial properties of wine have been studied only after the pressure treatment, without ever having references on the influence of the treatment in wine properties during storage. Then, the effect of HHP on the physical–chemical characteristics on long term storage of wine is still largely unknown. This work shows that HHP treatments accelerate Maillard reactions during the white wine storage period. This reaction should be taken into consideration in the implementation of HHP treatments to wine conservation as alternative to SO 2 .

ResumoIntroduçãoO sangue é importante recurso em diversas intervenções mantenedoras da vida, como corrigir a anemia e melhorar a capacidade de transporte de oxigênio. Apesar dos avanços, a transfusão de concentrado de hemácias (TCH) ainda envolve riscos. O objetivo deste estudo foi descrever o conhecimento dos anestesiologistas sobre as indicações, os efeitos adversos e as opções ao procedimento de transfusão de concentrado de hemácias no intraoperatório.MétodoEstudo transversal que usou questionário com perguntas de múltipla escolha e casos clínicos, referentes a fatores relevantes na decisão de transfundir concentrado de hemácias, seus efeitos adversos, gatilhos de hemoglobina, suas medidas preventivas e estratégias de conservação de sangue. Respondido sem a presença do pesquisador. Usada a escala de Likert e feito cálculo do ranking médio das respostas. Análise dos dados feita com programa Epi Info 7.ResultadosDos anestesiologistas da instituição, 79% responderam ao questionário e 100% identificaram os principais efeitos adversos relacionados à hemotransfusão. Questionados sobre os fatores que influenciariam na decisão de transfundir, o nível de hemoglobina obteve a maior concordância (RM=4,46), seguido de cardiopatia (RM=4,26), níveis de hematócrito (RM=4,34), idade (RM=4,1) e avaliação da microcirculação (RM=4,22). Dos entrevistados, 82,3% identificaram níveis de Hb=6g/dL como gatilho para transfundir paciente sadio. Quanto às estratégias de conservação de sangue, a hemodiluição hipervolêmica (RM=2,81) e a deliberada por medicamentos (RM=2,95) foram as menos citadas.ConclusãoIdentificou‐se uma boa compreensão dos anestesiologistas a respeito da TCH. No entanto, há necessidade de cursos de atualização sobre o tema.AbstractIntroductionBlood is an important resource in several lifesaving interventions, such as anemia correction and improvement of oxygen transport capacity. Despite advances, packed red blood cell (PRBC) transfusion still involves risks. The aim of this study was to describe the knowledge of anesthesiologists about the indications, adverse effects, and alternatives to red blood cell transfusion intraoperatively.MethodCross‐sectional study using a questionnaire containing multiple choice questions and clinical cases related to relevant factors on the decision whether to perform PRBC transfusion, its adverse effects, hemoglobin triggers, preventive measures, and blood conservation strategies. The questionnaire was filled without the presence of the investigator. Likert scale was used and the average rank of responses was calculated. The Epi Info 7 software was used for data analysis.Results79% of the institution's anesthesiologists answered the questionnaire; 100% identified the main adverse effects related to blood transfusion. When asked about the factors that influence the transfusion decision, hemoglobin level had the highest agreement (MR=4.46) followed by heart disease (MR=4.26); hematocrit (MR=4.34); age (RM=4.1) and microcirculation evaluation (MR=4.22). 82.3% of respondents identified levels of Hb=6g/dL as a trigger to transfuse healthy patient. Regarding blood conservation strategies, hypervolemic hemodilution (MR=2.81) and decided by drugs (MR=2.95) were the least reported.ConclusionWe identify a good understanding of anesthesiologists about PRBC transfusion; however, there is need for refresher courses on the subject.

4-(1,3-Benzothiazol-2-yl)thiophene-2-sulfonamide (4a) was found to be a moderately potent inhibitor of cyclin-dependent kinase 5 (cdk5) from a HTS screen. The synthesis and SAR around this hit is described. The X-ray coordinates of ligand 4a with cdk5 are also reported, showing an unusual binding mode to the hinge region via a water molecule.

Cetaceans are difficult to observe in the wild, and demand complex logistics for dedicated collection of biological data. As such, the distribution of most cetacean species is still poorly understood. Ecological niche models are useful in studying species distributions and their ecological determinants, and platforms of opportunity (e.g. commercial nautical operators) can provide an alternative source for that data in cetaceans. In this study, we modelled common dolphin (Delphinus delphis) habitat preferences using ecological niche modelling and presence data obtained from distinct platforms of opportunity in two different areas in the Portuguese coast (west and south mainland Portugal) for the period 2005e2007. Models from southern Portugal were projected to western Portugal and vice-versa, to check for robustness in predicting the species ecological niche. Our results show that data from platforms of opportunity can result in robust ecological models and provide extremely useful information on cetacean ecology. We found that common dolphins exhibit a patchy distribution pattern over the Portuguese coastline, and identified key habitats for their occurrence. The most important variable associated with this species’ distribution was chlorophyll concentration which, given the results from previous research, we hypothesise reflects an ecological specialisation on pelagic schooling fish. Given that the most abundant schooling fish species in Portugal is increasingly overexploited and in constant decline, more attention should be given to the conservation of common dolphin in Portuguese waters.

The Pd 0.15 SiBEA and Co x Pd 0.15 SiBEA zeolites (where x = 1.0 and 3.0 wt.% Co) are prepared by a two-step postsynthesis method which allows to control the introduction of palladium and cobalt into zeolite and thus to obtain catalysts with specific bimetallic Pd and Co sites. The effect of Co content on the catalytic activity of Co x Pd 0.15 SiBEA zeolites in the selective catalytic reduction (SCR) of NO with methane is investigated. The nature of the active sites is characterized by diffuse reflectance UV–vis, H 2 -TPR and XPS. These techniques allow to show that in both Co 1.0 Pd 0.15 SiBEA and Co 3.0 Pd 0.15 SiBEA catalysts the cobalt is present as isolated mononuclear Co(II) species. The catalytic activity of Co x Pd 0.15 SiBEA strongly depends on the content of this particular Co(II) species. When Co content increase from 1.0 to 3.0 wt.% the NO conversion in SCR of NO with methane increase from maximum value of 25% to 55%. The conversion of methane is lower than 15% for Co 1.0 Pd 0.15 SiBEA over a wide temperature range (230–460 °C) but for Co 3.0 Pd 0.15 SiBEA is much higher at temperature range between 400 and 500 °C reaching maximum value of 35% at 500 °C.

RESUMO - Este artigo tem como objetivo fazer uma revisão sobre o marketing de géneros alimentícios dirigido a crianças e sobre a sua possível relação com a obesidade infantil. O marketing de alimentos e bebidas, particularmente de elevada densidade energética e pobres em micronutrientes, pode ser, entre outros, um dos fatores que contribuem para a obesidade infantil pela sua influência negativa nos padrões de consumo alimentar das crianças. Existe alguma evidência de que o marketing influencia as crianças relativamente às suas escolhas, consumos e preferências alimentares, compras de alimentos e bebidas e pedidos que fazem destes produtos aos pais. Apesar dos níveis crescentes da prevalência da obesidade infantil, a maior parte dos alimentos publicitados dirigidos a crianças são ricos em calorias, gordura, açúcar e/ou sal, o que levanta sérias preocupações Éticas e de Saúde Pública, já que as crianças representam um alvo bastante vulnerável pela sua incapacidade de perceção das intenções persuasivas da publicidade. Medidas para controlar o marketing de alimentos dirigido a crianças poderão ser importantes na prevenção da obesidade infantil. ABSTRACT - This article is a review about food marketing directed to children and its possible relation to childhood obesity. Marketing of food and beverages, especially of those high in energy density and poor in micronutrients, can be one factor, among others, that contributes to childhood obesity by its negative influence on food consumption behaviour of children. There is some evidence that marketing influences children’s food choices, preferences and consumption, food and beverage purchases and requests of these products to parents. Although the prevalence of childhood obesity is increasing, most of the advertised foods to children are rich in calories, fat, sugar and/or salt, which is a main concerning of Ethics and Public Health. Children represent a vulnerable target of marketing because of their inability to understand its persuasive intentions. Measures to control food marketing directed to children could be important in preventing childhood obesity. info:eu-repo/semantics/publishedVersion

Although onion (Allium cepa L.) bulbs are good sources of phenolic compounds, the levels of these secondary metabolites are highly variable, depending on the cultivar, production, metereological conditions and post-harvest practices. The aim of this study was to characterize the interannual variation of flavonoid content in two Portuguese landrace varieties of onion (‘Branca da Povoa’, white, and ‘Vermelha da Povoa’, red), grown in the Spring–Summer of 2004, 2005, 2006, 2007 and 2008. HPLC-DAD was used to determine flavonoid concentration. Quercetin 3,4 0 -diglucoside and quercetin 4 0 -monoglucoside were the main flavonols in both varieties. Additionally, six cyanidin derivatives were identified in the red variety. Total and individual flavonoids levels varied significantly among seasons, with higher levels in 2005, a very dry and hot season. The red onion variety did not accumulate detectable amounts of anthocyanins in 2007, the year with the lowest air and soil temperature and highest soil water content.

Onions are rich in different types of phenolics, mainly flavonols, and in red varieties anthocyanins are also present. This is significant because these classes of phenolics are antioxidants and hence may impart important functional properties to onions. The aim of the present work was to simultaneously determine flavonol and anthocyanin concentrations in different onion varieties, two white (Branca da Povoa and the hybrid SK409) and three red (landrace Vermelha da Povoa, a selected line of Vermelha da Povoa and Red Creole). Flavonols (quercetin 7,4-diglucoside, quercetin 3,4-diglucoside, isorhamnetin 3,4-diglucoside, quercetin 3-glucoside, quercetin 4-glucoside and isorhamnetin 4-glucoside) were the predominant polyphenolic compounds. White cultivars had the lowest total flavonol content, with values of 89.3 ± 38.5 and 101.0 ± 18.9 mg quercetin/kg fresh weight for Branca da Povoa and the hybrid SK409, respectively. The red onions had the highest levels of flavonols, especially the selected population of Vermelha da Povoa and Red Creole, with values of 280.2 ± 41.5 and 304.3 ± 81.2 mg quercetin/kg fresh weight, respectively. Red onions are not only richer in flavonols, but also contain anthocyanins. Four anthocyanins (cyanidin 3-glucoside, cyanidin 3-laminaribioside, cyanidin 3-(6″-malonylglucoside), and cyanidin 3-malonylaminaribioside) were quantified in all red onions, with Red Creole presenting the highest concentration (28.6 ± 8 mg cyanidin/kg fresh weight). Red onions may be recommended for their major potential functional properties. A distinct gradient in total flavonoid content was found between the outer, central and inner edible scales and along the longitudinal axis of the bulb. Differences in flavonol levels between small- and large-sized onions were also found. All of these factors are of paramount importance for sampling and characterizing onions with regard to flavonoids.

The stability of the major flavonol glucosides and anthocyanins was studied in two regional varieties of Portuguese onion (a white variety “branca da Povoa” and a red variety “vermelha da Povoa”). White and red onions from 2007 and 2008 harvests were subjected to field curing with and without light, but the red cultivar from 2008 was also subjected to typical domestic processing, including chopping and different cooking treatments. Field curing resulted in increases in quercetin content compared to levels at lifting, especially important for all white bulbs (33–40% increase). Flavonol and anthocyanin levels in onions cured in the dark were similar to those obtained in bulbs cured in the light. The treatments chopping followed by refrigerated storage, oven roasting and frying, did practically not contribute to modify the total levels of flavonols. Moderate microwave cooking did not affect to the flavonol content, but intense microwave treatment cause flavonol losses of 16% and 18% for quercetin 3,4′-diglucoside (QdG) and quercetin 4′-glucoside (QmG), respectively. Boiling onions for 30 min leaded losses of quercetin glycosides, which leached to the boiling water without being degraded at 37% and 29% for QdG and QmG, respectively. Boiling for 60 min had more severe effects, since it caused the degradation of quercetin derivatives at 53% and 44% for QdG and QmG, respectively. For anthocyanins, the severity of the cooking treatments was in the following order: frying > boiling > roasting (microwave roasting > oven roasting).

SummaryCentrioles are microtubule-based cylindrical structures that exhibit 9-fold symmetry and facilitate the organization of centrosomes, flagella, and cilia [1]. Abnormalities in centrosome structure and number occur in many cancers [1, 2]. Despite its importance, very little is known about centriole biogenesis. Recent studies in C. elegans have highlighted a group of molecules necessary for centriole assembly [1, 3]. ZYG-1 kinase recruits a complex of two coiled-coil proteins, SAS-6 and SAS-5, which are necessary to form the C. elegans centriolar tube, a scaffold in centriole formation [4, 5]. This complex also recruits SAS-4, which is required for the assembly of the centriolar microtubules that decorate that tube [4, 5]. Here we show that Drosophila SAS-6 is involved in centriole assembly and cohesion. Overexpression of DSAS-6 in syncitial embryos led to the de novo formation of multiple microtubule-organizing centers (MTOCs). Strikingly, the center of these MTOCs did not contain centrioles, as described previously for SAK/PLK4 overexpression [6]. Instead, tube-like structures were present, supporting the idea that centriolar assembly starts with the formation of a tube-like scaffold, dependent on DSAS-6 [5]. In DSAS-6 loss-of-function mutants, centrioles failed to close and to elongate the structure along all axes of the 9-fold symmetry, suggesting modularity in centriole assembly. We propose that the tube is built from nine subunits fitting together laterally and longitudinally in a modular and sequential fashion, like pieces of a layered “hollow” cake.

In this study we aimed at investigating the incidence and the role of 3p deletions, particularly at the 3p25 approximately pter region, in follicle cell-derived thyroid neoplasms, by using loss of heterozygosity (LOH) analysis. We analyzed 12 follicular adenomas (FA), 13 follicular thyroid carcinomas (FTC), and 15 papillary thyroid carcinomas (PTC) with 11 microsatellite markers for chromosome 3. One additional marker on 3q25.2 was also investigated for assessment of deletion extent on 3q. Microsatellite instability was detected at one locus in 1 of 15 PTC (7%) and at four loci in 1 of 13 FTC (8%). Loss of heterozygosity was found in 8 of 12 cases of FTC (67%), in 6 of 15 cases of PTC (40%), and in 2 of 12 FA (17%). We identified three minimal common deleted regions (CDR) involving significant sites of LOH: two in FTC (a new terminal region, of approximately 8 cM distal to D3S1620 at 3p25.3 approximately pter and the D3S1573-D3S1595 region at 3p21.2 approximately p12) and one in PTC (D3S1304-D3S1263 region at 3p25.3 approximately p24.2). The newly identified 3p25.3 approximately pter CDR seems to be specific for FTC. Our results suggest the existence of at least three distinct regions on 3p that might harbor tumor suppressor genes involved in the carcinogenesis processes of FTC and PTC.