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All-trans-retinoic acid (ATRA), the most biologically active metabolite of vitamin A, controls cell proliferation, apoptosis, and differentiation depending on the cellular context. These activities point to ATRA as a candidate for cancer therapy. A pivotal effect of the molecule is the modulation of p27Kip1, a cyclin-dependent kinase (CDK) inhibitor (CDKI). Here, we investigate the mechanisms by which ATRA regulates p27Kip1 level in LAN-5, a neuroblastoma cell line. When added to the cells, ATRA causes a rapid nuclear increase of p27Kip1, which clearly precedes growth arrest. The early buildup is not due to impairment of the CDKI degradation, in contrast to previous observations. Particularly, we did not detect the down-regulation of Skp2 and Cks1, two proteins involved in the nuclear ubiquitin-dependent p27Kip1 removal. Moreover, the morphogen does not impair the CDKI nuclear export and does not cause CDK2 relocalization. The characterization of CDKI isoforms by two-dimensional PAGE/immunoblotting showed that ATRA induces an early nuclear up-regulation of monophosphorylated p27Kip1. Immunologic studies established that this isoform corresponds to p27Kip1 phosphorylated on S10. The buildup of phospho(S10)p27Kip1 precedes the CDKI accumulation and increases its half-life. Finally, ATRA-treated nuclear LAN-5 extracts showed an enhanced capability of phosphorylating p27Kip1 on S10, thus explaining the nuclear up-regulation of the isoform. In conclusion, our data suggest a novel mechanism of ATRA antiproliferative activity, in which the morphogen rapidly up-regulates a nuclear kinase activity that phosphorylates p27Kip1 on S10. In turn, this event causes the stabilization of p27Kip1 and its accumulation in the nuclear compartment. (Cancer Res 2006; 66(8): 4240-8)

Supplementary Materials and Methods from Retinoic Acid Induces p27Kip1 Nuclear Accumulation by Modulating Its Phosphorylation

Bakgrunn: Innvandrere utgjør 15 % av befolkningen, men representerer 30–40 % av positive tilfeller av covid-19 i Norge. Inngripende smitteverntiltak og nedstengning fører til nedgang i økonomien. Matusikkerhet oppstår i situasjoner med begrenset eller usikker tilgang til ernæringsmessig tilstrekkelig og trygg mat og kan bli påvirket av krisesituasjoner. Målet med prosjektet var å undersøke matusikkerhet blant hele befolkningen og innvandrere under den første fasen av koronapandemien. Metode: I en ekstra runde av Medborgerpanelet (NMP) svarte 4025 personer på spørsmålet «I løpet av koronapandemien, har du vært bekymret for at du vil gå tom for mat før du kan kjøpe igjen?». Samme spørsmål oversatt til fem språk (somalisk, polsk, tamil, arabisk og spansk) ble besvart av 529 innvandrere som del av studien Inncovid.Norge noen uker etter. Hovedfunn: Blant NMP-respondentene hadde 16 % noen gang og 1 % ofte vært bekymret for å gå tom for mat. Tilsvarende prosenter var 31 % og 7 % for innvandrere, men med forskjeller mellom gruppene. Konklusjon: Koronapandemien påvirker matsikkerhet i det norske samfunnet og rammer innvandrere spesielt. Evaluering og dekning av slike basale behov burde bli prioritert av myndighetene.

Background Dying at home is the most frequent preference of patients with advanced chronic conditions, their caregivers, and the general population. However, most deaths continue to occur in hospitals. The objective of this study was to analyse the socioeconomic inequalities in the place of death in urban areas of Mediterranean cities during the period 2010–2015, and to assess if such inequalities are related to palliative or non-palliative conditions. Methods This is a cross-sectional study of the population aged 15 years or over. The response variable was the place of death (home, hospital, residential care). The explanatory variables were: sex, age, marital status, country of birth, basic cause of death coded according to the International Classification of Diseases, 10th revision, and the deprivation level for each census tract based on a deprivation index calculated using 5 socioeconomic indicators. Multinomial logistic regression models were adjusted in order to analyse the association between the place of death and the explanatory variables. Results We analysed a total of 60,748 deaths, 58.5% occurred in hospitals, 32.4% at home, and 9.1% in residential care. Death in hospital was 80% more frequent than at home while death in a nursing home was more than 70% lower than at home. All the variables considered were significantly associated with the place of death, except country of birth, which was not significantly associated with death in residential care. In hospital, the deprivation level of the census tract presented a significant association (p Conclusions The probability of dying in hospital, as compared to dying at home, increases as the socioeconomic deprivation of the urban area of residence rises, both for palliative and non-palliative causes. Further qualitative research is required to explore the needs and preferences of low-income families who have a terminally-ill family member and, in particular, their attitudes towards home-based and hospital-based death.

Spain&rsquo, s population has changed thanks to recent immigration. Therefore, a new epidemiological and demographic profile has been generated in the country. This study aims to analyze immigrant and native cancer mortality trends in Spain for the period 2000 to 2016. An ecological study of trends was carried out. Age-standardized rates of cancer mortality (ASR) and annual percentage change (APC) between groups and study sub-periods were calculated. Significant decreases in ASR were observed for cancer in both the native and the immigrant populations, in both men and women. However, in 2014&ndash, 2016, there was an increase in ASR in the immigrant population compared to 2011&ndash, 2013, due to the increase in ASR among immigrants from European regions. Differences in ASR by cancer between immigrant and native populations residing in Spain have been identified, both in the rate of decline and magnitude as well as by the birth region of the immigrant population. The increase observed in the cancer mortality trend at the end of the period in some immigrant groups indicates the need to monitor these indicators given the demographic, social, and economic changes.

Many studies have analysed socioeconomic inequalities and its association with mortality in urban areas. However, few of them have differentiated between native and immigrant populations. This study is an ecological study of mortality by overall mortality and analyses the inequalities in mortality in these populations according to the level of deprivation in small areas of large cities in the Valencian Community, from 2009 to 2015. The census tract was classified into five deprivation levels using an index based on socioeconomic indicators from the 2011 census. Rates and relative risks of death were calculated by sex, age, level of deprivation and country of birth. Poisson regression models have been used. In general, there was a higher risk of death in natives at the levels of greatest deprivation, which did not happen in immigrants. During the 2009&ndash, 2015 period, there were socioeconomic inequalities in mortality, particularly in natives, who presented a higher risk of death than immigrants. Future interventions and social policies should be implemented in order to reduce inequalities in mortality amongst socioeconomic levels and to maintain the advantage that the immigrant population enjoys.

Several studies have described a decreasing trend in amenable mortality, as well as the existence of socioeconomic inequalities that affect it. However, their evolution, particularly in small urban areas, has largely been overlooked. The aim of this study is to analyse the socioeconomic inequalities in amenable mortality in three cities of the Valencian Community, namely, Alicante, Castellon, and Valencia, as well as their evolution before and after the start of the economic crisis (2000&ndash, 2007 and 2008&ndash, 2015). The units of analysis have been the census tracts and a deprivation index has been calculated to classify them according to their level of socioeconomic deprivation. Deaths and population were also grouped by sex, age group, period, and five levels of deprivation. The specific rates by sex, age group, deprivation level, and period were calculated for the total number of deaths due to all causes and amenable mortality and Poisson regression models were adjusted in order to estimate the relative risk. This study confirms that the inequalities between areas of greater and lesser deprivation in both all-cause mortality and amenable mortality persisted along the two study periods in the three cities. It also shows that these inequalities appear with greater risk of death in the areas of greatest deprivation, although not uniformly. In general, the risks of death from all causes and amenable mortality have decreased significantly from one period to the other, although not in all the groups studied. The evolution of death risks from before the onset of the crisis to the period after presented, overall, a general pro-cyclical trend. However, there are population subgroups for which the trend was counter-cyclical. The use of the deprivation index has made it possible to identify specific geographical areas with vulnerable populations in all three cities and, at the same time, to identify the change in the level of deprivation (ascending or descending) of the geographical areas throughout the two periods. It is precisely these areas where more attention is needed in order to reduce inequalities.

At model scale propellers, conventional turbulence models assume turbulent regimes all over the blade surface, and consequently do not obtain accurate predictions that can be compared to experimental results. Two aspects could be improved in order to produce a better description of the flow complexity generated in these turbulent rotating systems: the inclusion of transition phenomena assumptions that normally take place in these flows and a particular modeling of those transition mechanisms, such as cross flow, that appear at model scale propellers. In this paper, a new modified γ − R e θ correlation-based model for transition prediction, that takes into account crossflow effects is applied to model scale ship propellers for a wide range of advanced ratios, and its results are compared to their corresponding experimental results. The average values of the skin friction coefficients on different parts of the blade and the streamlines distribution are studied and compared between different propellers. The results obtained with these improvements show an agreement of about 1% in terms of efficiency, and below 5% in terms of thrust and torque coefficients when compared to the experimental results at the design point. The dependance of the cross flow mechanism on the Reynolds number is studied by changing the rotating velocity of the different propellers. Results show that the relevance of this mechanism grows when the rotating velocity, the centrifugal forces and Reynolds number increase. Consequently, when the Reynolds numbers grows, the cross flow transition mechanism is stimulated by the action of the centrifugal forces.

All ships acquire a dynamic trim and sinkage when they are in motion. These dynamic parameters depend on the hull shape and the velocity. The ship at rest already has a specific trim, the difference between the draft forward and the draft aft, due to its loading condition. Once in motion, and because of the pressure distribution along the hull, the ship reaches a new equilibrium condition, which is stationary if the ship’s velocity is kept constant and no sea state is considered. Although there are many publications devoted to optimizing the trim to obtain the minimum drag, the same cannot be said regarding the sinkage that appears to have been forgotten from any consideration. This work is dedicated to analyzing the sinkage phenomenon that the ship suffers when it is in motion. The aim is to quantify the prejudicial effect that the sinkage has over the drag resistance, both from the numerical and experimental points of view. Finally, the last purpose is to evaluate the effect of the hull shape on this phenomenon, whose assessment allows for the reaching of a hull shape optimization.

In this work, a coating of chitosan onto alginate hydrogels was realized using the water-soluble hydrochloride form of chitosan (CH-Cl), with the dual purpose of imparting antibacterial activity and delaying the release of hydrophilic molecules from the alginate matrix. Alginate hydrogels with different calcium contents were prepared by the internal setting method and coated by immersion in a CH-Cl solution. Structural analysis by cryo-scanning electron microscopy was carried out to highlight morphological alterations due to the coating layer. Tests in vitro with human mesenchymal stromal cells (MSC) were assessed to check the absence of toxicity of CH-Cl. Swelling, stability in physiological solution and release characteristics using rhodamine B as the hydrophilic model drug were compared to those of relative uncoated hydrogels. Finally, antibacterial activity against Escherichia coli was tested. Results show that alginate hydrogels coated with chitosan hydrochloride described here can be proposed as a novel medicated dressing by associating intrinsic antimicrobial activity with improved sustained release characteristics.

Bone marrow mesenchymal stromal cells (BM-MSCs) are multipotent cells capable of differentiating toward osteoblatic and adipocytic phenotypes. BM-MSCs play several key roles including bone remodeling, establishment of hematopoietic niche and immune tolerance induction. Here, we investigated the effect of resveratrol (RSV), a therapeutically promising natural polyphenol, on the commitment of human BM-MSCs primary cultures. Cell differentiation was evaluated by means of morphological analysis, specific staining and expression of osteogenic and adipocytic master genes (Runx-2, PPARγ). To maintain BM-MSC multipotency, all experiments were performed on cells at very early passages. At any concentration RSV, added to standard medium, did not affect the phenotype of confluent BM-MSCs, while, when added to osteogenic or adipogenic medium, 1 μM RSV enhances the differentiation toward osteoblasts or adipocytes, respectively. Conversely, the addition of higher RSV concentration (25 μM) to both differentiation media resulted exclusively in BM-MSCs adipogenesis. Surprisingly, the analysis of RSV molecular effects demonstrated that the compound completely substitutes insulin, a key component of adipogenic medium. We also observed that RSV treatment is associated to enhanced phosphorylation of CREB, a critical effector of insulin adipogenic activity. Finally, our observations contribute to the mechanistic elucidation of the well-known RSV positive effect on insulin sensitivity and type 2 diabetes mellitus.

In this paper, physico-chemical, mechanical and antimicrobial properties of hydrogels based on alginate/N-succinylchitosan blends crosslinked by calcium or zinc ions containing cellulose microfibers were investigated and discussed. With respect to plain alginate hydrogels, the addition of N-succinylchitosan significantly improved properties such as swelling degree and stability in saline solution. The water vapour transmission rate confirmed that all the hydrogels were able to assure a moist wound environment. Morphological analysis showed a good embedding of fibres within the zinc crosslinked hydrogels. In addition, zinc-crosslinked hydrogels evidenced antimicrobial activity against two common skin pathogenic bacteria, Staphylococcus aureus and Escherichia coli. Cytotoxicity assays proved that the amount of zinc released is slightly over the toxic level. Overall, the characteristics of the zinc-crosslinked hydrogels showed their potential interest as materials for wound dressing.

"Plants produce many low molecular mass natural compounds endowed with biological activity. Among them, resveratrol (3,5,4'-trihydroxystilbene) has been demonstrated to be able to affect a plethora of pivotal cellular molecular processes, including transduction pathways and gene expression. These activities result, in turn, in several different cell phenotypes. Particularly, frequent effects of resveratrol treatment appear to be the reduction of growth and the activation of programmed cell death. Accordingly, a number of trials are currently under development to evaluate the possibility of using resveratrol in cancer therapy, both as single agent or in association with other anticancer compounds. However, some reports suggest that, at low concentrations, not only resveratrol does not inhibit the proliferation and\/or the survival of cells but, conversely, it induces proliferation and\/or protects cells against toxic agents. On the basis of these biphasic effects, it has been proposed that resveratrol belongs to the so-called hormetic compounds. Hormesis is an expression employed by toxicologists to describe a U-shaped (or J-shaped) dose response characterized by a beneficial effect at low doses and a toxic (or inhibitory) activity at high dose. In this review, we will reappraise data that might suggest or disprove that resveratrol is endowed with clear hormetic properties."

Background Iron overload syndromes include a wide range of diseases frequently associated with increased morbidity and mortality. Several organs are affected in patients with iron overload including liver, heart, joints, endocrine glands, and pancreas. Moreover, severe bone and hemopoietic tissue alterations are observed. Because of the role of bone marrow mesenchymal stromal cells (BM-MSCs) in bone turnover and hematopoiesis, iron effects on primary BM-MSCs cultures were evaluated. Methods Primary human BM-MSCs cultures were prepared and the effects of iron on their proliferation and differentiation were characterized by biochemical analyses and functional approaches. Results Addition of iron to the culture medium strongly increased BM-MSCs proliferation and induced their accelerated S phase entry. Iron enters BM-MSCs through both transferrin-dependent and transferrin-independent mechanisms, inducing the accumulation of cyclins E and A, the decrease of p27 Kip1 , and the activation of MAPK pathway. Conversely, neither apoptotic signs nor up-regulation of reactive oxygen species were observed. Iron inhibited both differentiation of BM-MSCs into osteoblasts and in vitro matrix calcification. These effects result from the merging of inhibitory activities on BM-MSCs osteoblastic commitment and on the ordered matrix calcification process. Conclusions We demonstrated that BM-MSCs are a target of iron overload. Iron accelerates BM-MSCs proliferation and affects BM-MSCs osteoblastic commitment, hampering matrix calcification. General Significance Our study reports, for the first time, that iron, at concentration found in overloaded patient sera, stimulates the growth of BM-MSCs, the BM multipotent stromal cell component. Moreover, iron modulates the physiological differentiation of these cells, affecting bone turnover and remodeling.

The typology and placement of antennal sensilla of the carrion beetles Oxelytrum erythrurum (Blanchard) and Oxelytrum apicalis (Brullé) (Coleoptera: Silphidae) were studied using scanning electron microscopy. Two types of sensilla chaetica, two types of sensilla trichodea, four types of sensilla basiconica, one type of sensilla coeloconica, and an unidentified type of sensillum were found in both species. Sensilla chaetica type 1 are found on the antennomeres proximal to antennal club (A1-A8); chaetica type 2 are found on the club (A9-A11). Sensilla trichodea are found on A9-A11; one type (T1) is found on the proximal portion of the club, the other type (T2) on the apical portion. Basiconica type 1 are found on the dorsal surface of A9-A11; they are much denser on the apical portion of the antennal club than on the proximal. In O. erythrurum, a nocturnal species of the Chaco-Pampean plain, T2 two are found on A10 and A11. In Oxelytrum apicale, a mountain species, probably diurnal, only A11 bears T2, but they are denser than in the other species. It is suggested that O. apicale depends more on contact chemoreception than O. erythrurum. The ventral surface of the antennal clubs shows no remarkable difference between species. © 2012 Sociedade Entomológica do Brasil. Fil: Oliva, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales “Bernardino Rivadavia”; Argentina

Objectives: The aim of this study was to analyse the topographic features of a novel nano-structured oxidized titanium implant surface and to evaluate its effect on the response of human bone marrow mesenchymal stem cells (BM-MSC) compared with a traditional turned surface. Methods: The 10 × 10 × 1 mm turned (control) and oxidized (test) titanium samples (P.H.I. s.r.l.) were examined by scanning electron microscopy (SEM) and atomic force microscopy (AFM) and characterized by height, spatial and hybrid roughness parameters at different dimensional ranges of analysis. Primary cultures of BM-MSC were seeded on titanium samples and cell morphology, adhesion, proliferation and osteogenic differentiation, in terms of alkaline phosphatase activity, osteocalcin synthesis and extracellular matrix mineralization, were evaluated. Results: At SEM and AFM analyses turned samples were grooved, whereas oxidized surfaces showed a more complex micro- and nano-scaled texture, with higher values of roughness parameters. Cell adhesion and osteogenic parameters were greater on oxidized (P

"INTRODUCTION:. Cell division cycle progression is achieved by a sequential and stringently concerted activation of a family of serine-threonine kinases, namely the cyclin-dependent kinases (CDKs). p27(Kip1) is a pivotal CDK inhibitor and a tight modulator of CDK-dependent phenotypes. Thus, p27(Kip1) plays a fundamental role in key cellular processes such as proliferation, differentiation, apoptosis, substrate adhesion and motility. Intriguingly, when p27(Kip1) is localized in the nucleus, it acts as an antiproliferative protein, while, in the cytosol, p27(Kip1) promotes cytoskeleton remodeling and might positively influence metastatization. Downregulation of p27(Kip1) nuclear level or its cytosolic mislocalization are consistently correlated with poor prognosis of numerous types of human epithelial and non-epithelial cancers.. AREAS COVERED:. This review illustrates the basic structural features of p27(Kip1) protein, its metabolism and alterations in human malignancies, along with describing anticancer strategies based on targeting p27(Kip1).. EXPERT OPINION:. Given the role of p27(Kip1) in the control of cell proliferation and its decreased level observed in malignancies with poor outcome, drugs able to handle the protein levels and localization might represent an important goal for novel specific and effective anticancer strategies. Although no convincing proofs have been reported, putative negative consequences of p27(Kip1) targeting might be also conceivable.. "

Objectives: The aim of the present study was to examine the behaviour of human bone marrow-derived mesenchymal stem cells (BM-MSC) to fluoride-modified grit-blasted (F-TiO) titanium surfaces compared with grit-blasted ones (TiO). Material and methods: Implant surfaces were analysed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). BM-MSC were isolated from healthy donors and grown on the implant surfaces. Cell adhesion and proliferation, type I collagen (Col I) synthesis, osteoblastic differentiation (in terms of alkaline phosphatase activity, osteocalcin synthesis and extracellular matrix mineralization) were assessed. Furthermore, the ability to affect the osteoblastic/osteoclastic balance in terms of osteoprotegerin (OPG) and activator of nuclear factor κ B ligand (RANKL) ratio was investigated. Results: F-TiO surface showed higher Sa values (P

Myiasis is the condition resulting from the invasion of tissues or organs of man or animals by dipterous larvae. The blowflies (Calliphoridae) of Argentina comprise several species that may cause myiasis by colonizing wounds or infected body orifices, and one specific parasite: Cochliomyia hominivorax. This species often causes traumatic myiasis in cattle, dogs and cats, and it is not rare in humans. The larvae consume living tissues, so they are dangerous unless speedily removed. Immediate operative exploration along with the removal of larvae and primary defect closure is recommended in every case. Here we report a case of myiasis in a scalp wound caused by blunt force trauma to the area, in a male patient with a case history of alcohol and drug abuse. Seventy-one living larvae were extracted from the wound and determined as C. hominivorax in the Forensic Entomology Laboratory. Given the aggressiveness of these larvae, specific and quick diagnosis as well as the application of appropriate treatment is crucial. Fil: Trombetta, Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Oliva, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; Argentina Fil: Galache, Viviana. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Bava, Javier. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina. Universidad Nacional de La Plata; Argentina Fil: Troncoso, Alcides. Universidad de Buenos Aires. Facultad de Medicina; Argentina

The production of PEEA microspheres with potential as carriers for protein oral delivery is described. PEEAs with different hydrophilicity were synthesized and characterized. Experiments showed that an increase in copolymer hydrophilicity gave particles less prone to cell interaction. BSA release profiles from PEEA microspheres demonstrated that an increase in polymer hydrophilicity was useful in limiting protein burst and modulating drug delivery rate by increasing PEEA degradability. These results show that fine-tuning of the hydrophilic/hydrophobic properties of PCL is essential for the formulation protein-loaded microspheres with specific properties.

Histone deacetylase inhibitors (HDACIs) represent a new class of targeted anticancer agents. Here, we evaluate the effects of butyrate (BuA) and other HDACIs on p57(Kip2), a cyclin-dependent kinase inhibitor (cki). We observed that inhibitors of class I/II histone deacetylases (HDACs), but not of class III HDACs, induce a remarkable accumulation of p57(Kip2) in several cells. The cki upregulation is associated with an increased gene expression that was not prevented by cycloheximide, indicating that HDACIs affect directly p57(Kip2) transcription. The characterization of p57(Kip2) promoter indicates that the first 165 bp are mostly involved in the BuA effects. Chromatin immunoprecipitation studies demonstrated that the BuA treatment causes the recruitment of Sp1 transcription factor. The Sp1 importance was confirmed by the reduction of BuA effects by mithramycin A (an Sp1 antagonist) and, most stringently, by Sp1 downregulation due to Sp1 siRNA. Moreover, both the treatments reduce the p57(Kip2) transcription in untreated cells, suggesting that Sp1 is required for the constitutive cki expression. Studies employing plasmids containing parts of the 165 bp of p57(Kip2) promoter indicate that the promoter region between -87 and -113 bp, which includes two putative Sp1 consensus sequences, plays a critical role in the response to HDACIs. Since this p57(Kip2) promoter region also embraces the consensus sequence for the transcriptional repressor chicken ovalbumin upstream promoter transcription factor-interacting protein 2 (CTIP2), we evaluated whether this factor is involved into the BuA effect. When CTIP2 was downregulated by a specific siRNA, we observed the enhancement of BuA activity on p57(Kip2) expression suggesting that CTIP2 might also be involved in HDACIs effects.

Frequency and temporal distribution of cadaveric flies (Diptera) in the city of Buenos Aires. Forensic entomology is used to estimate the post-mortem interval (PMI) by determination of the species of insects found on a corpse and their stage of development. The later varies according to environtmental conditions; in temperate climates the occurrence of each species varies seasonally. The Order Diptera is the most important in the early stages of decomposition. Only fragmentary data on temporal distibution in Buenos Aires have been published, and these were only based on trapping and rearing. This paper is based on records of forensic ntomology expertises performed in the year period 1995-2005. The occurrences of Calliphora vicina, e Phaenicia sericata, Cochliomyia macellaria and Chrysomya albiceps (Calliphoridae), Sarcophaga spp (Sarcophagidae), Hydrotaea argentina and Muscina stabulans (Muscidae) and Megaselia scalaris (Phoridae), indoors and outdoors, is recorded. The predominance of C. vicina from autumn to spring and of P. sericata in summer is confirmed. The autochthonous C. macellaria was recorded the whole year, with a peak in the summer months; it proved rare outdoors. A species which may function as primary or secondary is C. albiceps; it is active in summer and early autumn. The species of Sarcophaga are active mainly in summer but they appear along the rest f the year associated with advanced decomposition. No marked seasonal variation was shown by H. argentina, M. stabulans, and M. scalaris.

PLoS one 10(1), 1-17 (2015). doi:10.1371/journal.pone.0116468, Published by PLoS, Lawrence, Kan.

In the present work, microporous membranes based on poly(e-caprolactone) (PCL) and PCL functionalized with amine (PCL-DMAEA) or anhydride groups (PCL-MAGMA) were realized by solvent–non solvent phase inversion and proposed for use in Guided Tissue Regeneration (GTR). Nanowhiskers of hydroxyapatite (HA) were also incorporated in the polymer matrix to realize nanocomposite membranes. Scanning Electron Microscopy (SEM) showed improved interfacial adhesion with HA for functionalized polymers, and highlighted substantial differences in the porosity. A relationship between the developed porous structure of the membrane and the chemical nature of grafted groups was proposed. Compared to virgin PCL, hydrophilicity increases for functionalized PCL, while the addition of HA influences significantly the hydrophilic characteristics only in the case of virgin polymer. A significant increase of in vitro degradation rate was found for PCL-MAGMA based membranes, and at lower extent of PCL-DMAEA membranes. The novel materials were investigated regarding their potential as support for cell growth in bone repair using multipotent mesenchymal stromal cells (MSC) as a model. MSC plated onto the various membranes were analyzed in terms of adhesion, proliferation and osteogenic capacity that resulted to be related to chemical as well as porous structure. In particular, PCL-DMAEA and the relative nanocomposite membranes are the most promising in terms of cell-biomaterial interactions.

All-trans-retinoic acid (ATRA), the most biologically active metabolite of vitamin A, controls cell proliferation, apoptosis, and differentiation depending on the cellular context. These activities point to ATRA as a candidate for cancer therapy. A pivotal effect of the molecule is the modulation of p27Kip1, a cyclin-dependent kinase (CDK) inhibitor (CDKI). Here, we investigate the mechanisms by which ATRA regulates p27Kip1 level in LAN-5, a neuroblastoma cell line. When added to the cells, ATRA causes a rapid nuclear increase of p27Kip1, which clearly precedes growth arrest. The early buildup is not due to impairment of the CDKI degradation, in contrast to previous observations. Particularly, we did not detect the down-regulation of Skp2 and Cks1, two proteins involved in the nuclear ubiquitin-dependent p27Kip1 removal. Moreover, the morphogen does not impair the CDKI nuclear export and does not cause CDK2 relocalization. The characterization of CDKI isoforms by two-dimensional PAGE/immunoblotting showed that ATRA induces an early nuclear up-regulation of monophosphorylated p27Kip1. Immunologic studies established that this isoform corresponds to p27Kip1 phosphorylated on S10. The buildup of phospho(S10)p27Kip1 precedes the CDKI accumulation and increases its half-life. Finally, ATRA-treated nuclear LAN-5 extracts showed an enhanced capability of phosphorylating p27Kip1 on S10, thus explaining the nuclear up-regulation of the isoform. In conclusion, our data suggest a novel mechanism of ATRA antiproliferative activity, in which the morphogen rapidly up-regulates a nuclear kinase activity that phosphorylates p27Kip1 on S10. In turn, this event causes the stabilization of p27Kip1 and its accumulation in the nuclear compartment. (Cancer Res 2006; 66(8): 4240-8)

p27Kip1 is a critical modulator of cell proliferation by controlling assembly, localization and activity of cyclin-dependent kinase (CDK). p27Kip1 also plays important roles in malignant transformation, modulating cell movement and interaction with the extracellular matrix. A critical p27Kip1 feature is the lack of a stable tertiary structure that enhances its "adaptability" to different interactors and explains the heterogeneity of its function. The absence of a well-defined folding underlines the importance of p27Kip1 post-translational modifications that might highly impact the protein functions. Here, we characterize the metabolism and CDK interaction of phosphoserine10-p27Kip1 (pS10- p27Kip1), the major phosphoisoform of p27Kip1. By an experimental strategy based on specific immunoprecipitation and bidimensional electrophoresis, we established that pS10-p27Kip1 is mainly bound to cyclin E/CDK2 rather than to cyclin A/CDK2. pS10- p27Kip1 is more stable than non-modified p27Kip1, since it is not (or scarcely) phosphorylated on T187, the post-translational modification required for p27Kip1 removal in the nucleus. pS10-p27Kip1 does not bind CDK1. The lack of this interaction might represent a mechanism for facilitating CDK1 activation and allowing mitosis completion. In conclusion, we suggest that nuclear p27Kip1 follows two almost independent pathways operating at different rates. One pathway involves threonine-187 and tyrosine phosphorylations and drives the protein towards its Skp2-dependent removal. The other involves serine-10 phosphorylation and results in the elongation of p27Kip1 half-life and specific CDK interactions. Thus, pS10-p27Kip1, due to its stability, might be thought as a major responsible for the p27Kip1-dependent arrest of cells in G1/G0 phase.

Objectives: Platelet-rich plasma is a blood-derived fraction containing high concentrations of platelets and growth factors. Applied in the form of a gel on surgical wounds, it is able to stimulate hard and soft tissue repair and has been proposed for use in the field of periodontal regeneration. However to date, little is known about the biological interactions between platelet-rich plasma and periodontally related cells. In this study, we investigated the effects between platelet-rich plasma and cell populations involved in periodontal regeneration, namely primary human periodontal ligament cells, gingival fibroblasts and keratinocytes. Material and methods: The proliferation of human periodontal ligament cells, gingival fibroblasts and keratinocytes by [3H]thymidine incorporation was assessed. The alkaline phosphatase activity and type I collagen levels of human periodontal ligament cells were also evaluated by a spectrophotometric assay and western blot analysis, respectively. Results: Incubation of human periodontal ligament cells with platelet-rich plasma resulted in time-dependent growth stimulation (up to fourfold of control at 72 h). Likewise, an increase in the specific activity of alkaline phosphatase (fourfold at 6 days) and collagen (twofold at 7 days) was observed. Platelet-rich plasma also enhanced human gingival fibroblasts proliferation by twofold, whereas it inhibited human keratinocytes growth by 40%, with respect to their own controls at 72 h. Conclusion: Cell populations related to periodontal tissue were differently affected by platelet-rich plasma. In fact, a strong stimulation of human periodontal ligament cells proliferation, a minor increase in the growth rate of human gingival fibroblasts and a marked decrease of human keratinocytes proliferation were evident. In addition, in human periodontal ligament cells increased collagen and alkaline phosphatase activity levels were observed. These findings appear interesting in view of platelet-rich plasma utilization in periodontal regeneration.

Hydroxyapatite (Ca-10(PO4)(6)(OH)(2)) is one of the most biocompatible ceramics because it is similar to the mineral constituents of human bone and teeth. Composites of hydroxyapatite (HA) and biodegradable polymers such as polycaprolactone (PCL) are interesting materials for medical applications, especially for bone replacement. With the aim to improve the properties of biodegradable polyester-based devices, we have prepared and characterized novel composites made of polycaprolactone and natural or synthetic hydroxyapatite. The composites were screened for cytocompatibility by a direct contact method, in view of the future application of these hydroxyapatite filled PCL polymers as scaffolds for bone engineering. Primary cultures of human bone marrow mesenchymal stem cells (MSC) were selected as the most appropriate models to study the in vitro performance of these materials. The results showed that all materials have good biocompatibility and allow expression of the osteoblastic features. Scanning electron microscopy provided direct evidence of intense cell adhesion and proliferation on the tested materials.

Differences in the succession of insects and other Arthropoda (invertebrate animals with jointed legs), on domestic pig carcasses placed under a roof and under the open sky have been studied in Buenos Aires Province, Argentina (latitude 34 degrees 45'S) in all the seasons of the year. Faunal associations proved different for each treatment in winter: the common bluebottle Calliphora vicina was found in both, but on the sheltered carcass Cochliomyia macellaria and the rare Phaenicia cluvia were found as well. In the fall, the difference between sheltered and unsheltered carcasses was small (six species on the former and five species on the latter); in spring and summer, the difference was negligible.

Samples of aquatic Coleoptera were taken from 9 sites in subtropical/temperate southern South-America. A new species and several new regional records are reported. The regional affinities of swimming and crawling Hydrophilidae in lentic habitats are discussed in the context of river basins.

Two new formulations of bioactive glasses were used as coatings on titanium alloy (TiAl6V4) implants for prosthetic applications in the orthopaedic field. The biocompatibility of these bioglasses, as well as their osteoconductive properties, were assessed by employing primary cultures of human osteoblasts. A nonbioactive glass, the titanium alloy and polystyrene surface were used as controls. The results obtained demonstrated that the two bioglasses elicited a rapid and strong proliferative response by osteoblasts, which spread, formed a close layer and then expressed the specific osteoblastic marker i.e. osteocalcin. In comparison, cells grew on the nonbioactive glass to a much minor extent, similar to that of polystyrene control, showing individual cellular elements not forming a compact sheet, but expressed levels of osteocalcin clearly higher than both the polystyrene control and the two bioglasses. Finally, a very low proliferative rate of osteoblasts and the synthesis of hardly detectable osteocalcin amounts were observed with the titanium alloy. In conclusion, our studies indicate that the new bioactive glasses are effective in stimulating osteoblast growth and differentiation.