The retinoblastoma protein:multitasking to suppress tumorigenesis

Tumor suppressor activity of the retinoblastoma protein pRB is preserved despite loss of interaction with E2F transcription factors (E2F) or proteins harboring a leucine-x-cysteine-x-glutamic acid motif (LxCxE, where x is any amino acid). This indicates that pRB uses several parallel pathways to suppress tumorigenesis, which may also include E2F- and LxCxE-independent interactions

Fauna de mosquitos asociada con Aedes aegypti en Guaduas, Colombia

Seven different species of mosquitoes were found sharing the natural habitat of Aedes aegypti, during a study of the ecology of this vector in Guaduas, Colombia. Low tanks used for laundry a (albercas) were the breeding places where Aedes aegypti exhibited the greatest degree of association with other species. Larvae of Toxorhynchites spp. were found in elevated water reservoirs. The relevante of these findings for the ecology and control of Aedes aegypti is discussed.Durante un estudio sobre la ecología del Aedes aegypti llevado a cabo en el área urbana de Guaduas, Colombia, se hallaron un total de siete especies de mosquitos que compartían hábitats con esta especie. Los criaderos en los cuales se encontró un mayor número de mosquitos asociados con el Aedes aegypti fueron los tanques bajos (albercas). Larvas de Toxorhynchites spp. se encontraron en tanques elevados. Se discute la importancia de estos hallazgos con relación a los aspectos de ecología y control del Aedes aegypti

Detecting critical choke points for achieving Good Environmental Status in European seas

Peer reviewedPublisher PD

“You Might Belong in Gryffindor”: Children’s Courage and Its Relationships to Anxiety Symptoms, Big Five Personality Traits, and Sex Roles

This study describes a first exploration of the construct of courage in youths. Children aged 8–13 years were invited to report on the most courageous action that they had ever performed during their life. In addition, the Courage Measure for Children (CM-C) was construed as an index of children’s level of personal courage, and this scale was administered in two samples of school children (Ns being 168 and 159) along with a number of other questionnaires. Results indicated that children were familiar with the concept of courage as more than 70% reported to have carried out a courageous action during their life. In addition, self-reported courage as indexed by the CM-C was positively correlated with scores on a vignette measure of courage, parent ratings of children’s courage, extraversion, openness/intellect, and a masculine sex role, whereas a negative correlation was observed with anxiety symptoms. The implications of these findings and potential directions for future research are briefly discussed

Is new drug prescribing in primary care specialist induced?

<p>Abstract</p> <p>Background</p> <p>Medical specialists are often seen as the first prescribers of new drugs. However, the extent to which specialists influence new drug prescribing in primary care is largely unknown.</p> <p>Methods</p> <p>This study estimates the influence of medical specialists on new drug prescribing in primary care shortly after market introduction. The influence of medical specialists on prescribing of five new drugs was measured in a cohort of 103 GPs, working in 59 practices, over the period 1999 until 2003. The influence of medical specialists on new drug prescribing in primary care was assessed using three outcome measures. Firstly, the proportion of patients receiving their first prescription for a new or reference drug from a specialist. Secondly, the proportion of GPs prescribing new drugs before any specialist prescribes to their patients. Thirdly, we compared the time until the GP's first own prescribing between GPs who waited for prescriptions from specialists and those who did not.</p> <p>Results</p> <p>The influence of specialists showed considerable differences among the new drugs studied. The proportion of patients receiving their first prescription from a specialist was greatest for the combination salmeterol/fluticasone (60.2%), and lowest for rofecoxib (23.0%). The proportion of GPs prescribing new drugs before waiting for prescriptions from medical specialists ranged from 21.1% in the case of esomeprazole to 32.9% for rofecoxib. Prescribing new drugs by specialists did not shorten the GP's own time to prescribing.</p> <p>Conclusion</p> <p>This study shows that the influence of medical specialists is clearly visible for all new drugs and often greater than for the existing older drugs, but the rapid uptake of new drugs in primary care does not seem specialist induced in all cases. GPs are responsible for a substantial amount of all early prescriptions for new drugs and for a subpopulation specialist endorsement is not a requisite to initiate in new drug prescribing. This contradicts with the idea that the diffusion of newly marketed drugs always follows a two-step model, with medical specialists as the innovators and GPs as the followers.</p

Advances in shape measurement in the digital world

The importance of particle shape in terms of its effects on the behaviour of powders and other particulate systems has long been recognised, but particle shape information has been rather difficult to obtain and use until fairly recently, unlike its better-known counterpart, particle size. However, advances in computing power and 3D image acquisition and analysis techniques have resulted in major progress being made in the measurement, description and application of particle shape information in recent years. Because we are now in a digital era, it is fitting that many of these advanced techniques are based on digital technology. This review article aims to trace the development of these new techniques, highlight their contributions to both academic and practical applications, and present a perspective for future developments

Development of a Two-Phase Scaffold-Nanoparticle System for the Sustained Delivery of Growth Factors in Bone Tissue Engineering Applications

In recent years, bone tissue engineering has emerged as a promising strategy to overcome the limitations of current ‘gold standard’ treatment options for bone disorders such as bone autografts and allografts. Bone tissue engineering strategies rely on the development of a scaffold that mimics the extracellular matrix, thereby providing an architecture that guides the natural bone regeneration process. Recently, scaffold systems have been developed to incorporate important extracellular signaling molecules which promote fracture healing and bone formation pathways. Among these signaling molecules, naturally occurring growth factors are of particular interest. This interest is due to their ability to enhance cell recruitment and ingress into the scaffold and promote osteogenic differentiation and angiogenesis, each of which is crucial to successful bone regeneration. However, a key challenge in growth factor delivery is that the molecule must reach the site of injury without losing bioactivity and remain in the location for an extended time in order to effectively aid in the formation of new bone. Among various strategies explored in the literature, incorporation of growth factors into particles can offer both protection of bioactivity and a sustained release profile. However, the particles can easily diffuse through the scaffold macropores and traverse to other areas of the body. In this work, a novel two-phase system for the sustained delivery of BMP-2 growth factors has been developed. The system consists of growth factors encapsulated in degradable nanoparticles (nanocarriers) which are immobilized in a porous scaffold. The nanoparticles incorporate a hydrolytically degradable crosslinker that can be easily tuned to achieve desired sustained release profiles. By chemically conjugating the nanocarriers to the scaffold backbone, this two-phase system is able to protect the growth factor from rapid degradation, improve the release kinetics, and achieve longer-term retention within the scaffold. Ultimately, the tunability of this novel growth factor delivery platform can be adapted to a wide variety of applications. Ultimately, this work shows that two-phase systems consisting of growth factor-loaded nanoparticles covalently bound to scaffolds have great promise, both by providing sustained release over a therapeutically relevant timeframe and the potential to sequentially deliver multiple growth factors

Etiology and early pathogenesis of malignant testicular germ cell tumors: towards possibilities for preinvasive diagnosis

Malignant testicular germ cell tumors (TGCT) are the most frequent cancers in Caucasian males (20-40 years) with an 70% increasing incidence the last 20 years, probably due to combined action of (epi) genetic and (micro) environmental factors. It is expected that TGCT have carcinoma in situ (CIS) as their common precursor, originating from an embryonic germ cell blocked in its maturation process. The overall cure rate of TGCT is more than 90%, however, men surviving TGCT can present long-term side effects of systemic cancer treatment. In contrast, men diagnosed and treated for CIS only continue to live without these long-term side effects. Therefore, early detection of CIS has great health benefits, which will require an informative screening method. This review described the etiology and early pathogenesis of TGCT, as well as the possibilities of early detection and future potential of screening men at risk for TGCT. For screening, a well-defined risk profile based on both genetic and environmental risk factors is needed. Since 2009, several genome wide association studies (GWAS) have been published, reporting on single-nucleotide polymorphisms (SNPs) with significant associations in or near the genes KITLG, SPRY4, BAK1, DMRT1, TERT, ATF7IP, HPGDS, MAD1L1, RFWD3, TEX14, and PPM1E, likely to be related to TGCT development. Prenatal, perinatal, and postnatal environmental factors also influence the onset of CIS. A noninvasive early detection method for CIS would be highly beneficial in a clinical setting, for which specific miRNA detection in semen seems to be very promising. Further research is needed to develop a well-defined TGCT risk profile, based on gene-environment interactions, combined with noninvasive detection method for CIS

Helical chirality induction of expanded porphyrin analogues

Malignant testicular germ cell tumors (TGCT) are the most frequent cancers in Caucasian males (20-40 years) with an 70% increasing incidence the last 20 years, probably due to combined action of (epi)genetic and (micro)environmental factors. It is expected that TGCT have carcinoma in situ(CIS) as their common precursor, originating from an embryonic germ cell blocked in its maturation process. The overall cure rate of TGCT is more than 90%, however, men surviving TGCT can present long-term side effects of systemic cancer treatment. In contrast, men diagnosed and treated for CIS only continue to live without these long-term side effects. Therefore, early detection of CIS has great health benefits, which will require an informative screening method. This review described the etiology and early pathogenesis of TGCT, as well as the possibilities of early detection and future potential of screening men at risk for TGCT. For screening, a well-defined risk profile based on both genetic and environmental risk factors is needed. Since 2009, several genome wide association studies (GWAS) have been published, reporting on single-nucleotide polymorphisms (SNPs) with significant associations in or near the genes KITLG, SPRY4, BAK1, DMRT1, TERT, ATF7IP, HPGDS, MAD1L1, RFWD3, TEX14, and PPM1E, likely to be related to TGCT development. Prenatal, perinatal, and postnatal environmental factors also influence the onset of CIS. A noninvasive early detection method for CIS would be highly beneficial in a clinical setting, for which specific miRNA detection in semen seems to be very promising. Further research is needed to develop a well-defined TGCT risk profile, base