Polycomb-mediated repression of EphrinA5 promotes growth and invasion of glioblastoma.

Glioblastoma (GBM) is the most common and most aggressive intrinsic brain tumour in adults. Integrated transcriptomic and epigenomic analyses of glioblastoma initiating cells (GIC) in a mouse model uncovered a novel epigenetic regulation of EfnA5. In this model, Bmi1 enhances H3K27me3 at the EfnA5 locus and reinforces repression of selected target genes in a cellular context-dependent fashion. EfnA5 mediates Bmi1-dependent proliferation and invasion in vitro and tumour formation in an allograft model. Importantly, we show that this novel Polycomb feed-forward loop is also active in human GIC and we provide pre-clinical evidence of druggability of the EFNA5 signalling pathway in GBM xenografts overexpressing Bmi1

Reproductive biology and ex situ conservation of the genus Restrepia (Orchidaeae)

The genus Restrepia is well known to orchid enthusiasts but its micromorphology has not been described, and its pollination and breeding systems have not been investigated. The aim of this investigation was, therefore, to add to existing knowledge so that the resultant data could be used to facilitate ex situ conservation initiatives. A detailed electron microscopy study (SEM) of the floral organs was performed. This confirmed the structure of the dorsal sepal and lateral petal osmophores, their secretory nature together with that of the synsepal and the labellum. It was postulated how, by manipulating different labellar surface textures, the flower might use these ‘tactile guides’ to steer the insect (fly) through the flower. The cirrhi were postulated to help by destabilising the pollinator in flight, trapping it and bringing about pollination. The papillate structure of the calli was established and their optical properties investigated. Media comparison investigations established that Western medium supported the highest germination rates and, with the addition of banana supplement, the highest rates for seedling growth and development. This represented the first protocol for axenic germination of Restrepia in the literature (Millner et al., 2008) and provided a tested methodology for investigating breeding systems and producing Restrepia plant material for both scientific and horticultural purposes. Self-pollinations were found to produce fewer embryos compared to cross-pollinations. The operation of self-incompatibility (SI) was confirmed by the study of pollen tube growth which further confirmed the time interval between pollination and fertilisation. A time line from pollination/fertilisation to flowering was established. The type of SI in operation was best explained by gametophytic incompatibility. This demonstrated that it was possible to raise Restrepia hybrids and species from seed, by performing intraspecific crosses so helping to preserve them for posterity and relieve pressure on wild populations. Narrow endemic Restrepia species face combined threats from habitat loss, habitat degradation and problems of viable seed production due to the effects of SI and inbreeding depression (ID). Recently developed online resources, such as GeoCAT, were used to perform a Red List assessment in order to identify the degree of threat individual species faced, both globally and nationally. All species were classified as facing substantial levels of threat; although this was lessened for populations in protected habitats. Conservation is needed for cultivated collections as well as these wild populations by keeping alive existing knowledge and expertise in growing these species.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Minimally invasive versus conventional aortic valve replacement: a propensity-matched study from the UK National Data

Minimally invasive aortic valve replacement (MIAVR) has been demonstrated as a safe and effective option but remains underused. We aimed to evaluate outcomes of isolated MIAVR compared with conventional aortic valve replacement (CAVR).Data from The National Institute for Cardiovascular Outcomes Research (NICOR) were analyzed at seven volunteer centers (2006-2012). Primary outcomes were in-hospital mortality and midterm survival. Secondary outcomes were postoperative length of stay as well as cumulative bypass and cross-clamp times. Propensity modeling with matched cohort analysis was used.Of 307 consecutive MIAVR patients, 151 (49%) were performed during the last 2 years of study with a continued increase in numbers. The 307 MIAVR patients were matched on a 1:1 ratio. In the matched CAVR group, there was no statistically significant difference in in-hospital mortality [MIAVR, 4/307,(1.3%); 95% confidence interval (CI), 0.4%-3.4% vs CAVR, 6/307 (2.0%); 95% CI, 0.8%-4.3%; P = 0.752]. One-year survival rates in the MIAVR and CAVR groups were 94.4% and 94.6%, respectively. There was no statistically significant difference in midterm survival (P = 0.677; hazard ratio, 0.90; 95% CI, 0.56-1.46). Median postoperative length of stay was lower in the MIAVR patients by 1 day (P = 0.009). The mean cumulative bypass time (94.8 vs 91.3 minutes; P = 0.333) and cross-clamp time (74.6 vs 68.4 minutes; P = 0.006) were longer in the MIAVR group; however, this was significant only in the cross-clamp time comparison.Minimally invasive aortic valve replacement is a safe alternative to CAVR with respect to operative and 1-year mortality and is associated with a shorter postoperative stay. Further studies are required in high-risk (logistic EuroSCORE > 10) patients to define the role of MIAVR

Chaos in an Exact Relativistic 3-body Self-Gravitating System

We consider the problem of three body motion for a relativistic one-dimensional self-gravitating system. After describing the canonical decomposition of the action, we find an exact expression for the 3-body Hamiltonian, implicitly determined in terms of the four coordinate and momentum degrees of freedom in the system. Non-relativistically these degrees of freedom can be rewritten in terms of a single particle moving in a two-dimensional hexagonal well. We find the exact relativistic generalization of this potential, along with its post-Newtonian approximation. We then specialize to the equal mass case and numerically solve the equations of motion that follow from the Hamiltonian. Working in hexagonal-well coordinates, we obtaining orbits in both the hexagonal and 3-body representations of the system, and plot the Poincare sections as a function of the relativistic energy parameter $\eta$. We find two broad categories of periodic and quasi-periodic motions that we refer to as the annulus and pretzel patterns, as well as a set of chaotic motions that appear in the region of phase-space between these two types. Despite the high degree of non-linearity in the relativistic system, we find that the the global structure of its phase space remains qualitatively the same as its non-relativisitic counterpart for all values of $\eta$ that we could study. However the relativistic system has a weaker symmetry and so its Poincare section develops an asymmetric distortion that increases with increasing $\eta$. For the post-Newtonian system we find that it experiences a KAM breakdown for $\eta \simeq 0.26$: above which the near integrable regions degenerate into chaos.Comment: latex, 65 pages, 36 figures, high-resolution figures available upon reques

Transmogrifying Fuzzy Vortices

We show that the construction of vortex solitons of the noncommutative Abelian-Higgs model can be extended to a critically coupled gauged linear sigma model with Fayet-Illiopolous D-terms. Like its commutative counterpart, this fuzzy linear sigma model has a rich spectrum of BPS solutions. We offer an explicit construction of the degree$-k$ static semilocal vortex and study in some detail the infinite coupling limit in which it descends to a degree$-k$ \C\Pk^{N} instanton. This relation between the fuzzy vortex and noncommutative lump is used to suggest an interpretation of the noncommutative sigma model soliton as tilted D-strings stretched between an NS5-brane and a stack of D3-branes in type IIB superstring theory.Comment: 21 pages, 4 figures, LaTeX(JHEP3

Prolonged institutional rearing is associated with atypically large amygdala volume and difficulties in emotion regulation

Early adversity, for example poor caregiving, can have profound effects on emotional development. Orphanage rearing, even in the best circumstances, lies outside of the bounds of a species-typical caregiving environment. The long-term effects of this early adversity on the neurobiological development associated with socio-emotional behaviors are not well understood. Seventy-eight children, who include those who have experienced orphanage care and a comparison group, were assessed. Magnetic resonance imaging (MRI) was used to measure volumes of whole brain and limbic structures (e.g. amygdala, hippocampus). Emotion regulation was assessed with an emotional go-nogo paradigm, and anxiety and internalizing behaviors were assessed using the Screen for Child Anxiety Related Emotional Disorders, the Child Behavior Checklist, and a structured clinical interview. Late adoption was associated with larger corrected amygdala volumes, poorer emotion regulation, and increased anxiety. Although more than 50% of the children who experienced orphanage rearing met criteria for a psychiatric disorder, with a third having an anxiety disorder, the group differences observed in amygdala volume were not driven by the presence of an anxiety disorder. The findings are consistent with previous reports describing negative effects of prolonged orphanage care on emotional behavior and with animal models that show long-term changes in the amygdala and emotional behavior following early postnatal stress. These changes in limbic circuitry may underlie residual emotional and social problems experienced by children who have been internationally adopted

Bilijarna funkcija u radnika profesionalno izloženih aluminijskoj prašini i dimu

This study investigated billiary secretory function in workers occupationally exposed to aluminium dust and fumes. It included a group of 34 male workers aged (44.1±7.8) years and exposed up to 4.6 mg m-3 of aluminium dust and fumes in workplace air for (21.6±2.5) years, and a group of 30 unexposed control male workers. Serum and urine aluminium levels were measured in both groups before and after chelating treatment with 1 g deferoxamine by intramuscular injection. Billiary function was assessed by measuring gamma-glutamyl transpeptidase, alkaline phosphatase, 5-nucleotidase, cholesterol and its fractions, total and indirect bilirubin, and bile acids. We then analysed the relationship between Al exposure and billiary function. In the exposed group mean serum aluminium was significantly higher [(4.91±3.86) µg L-1] than in controls. The same was true for urine Al before [(1.57±1.93) µg L-1] and after deferoxamine [(11.51±14.97) µg L-1]. Total and indirect bilirubin and alkaline phosphatase were significantly higher in the exposed than in control workers, and they correlated with urine Al after the chelating treatment. Our findings suggest that chronic occupational exposure to aluminium dust and fumes leads to a significant body retention of aluminium. The impaired biliary secretion in the exposed workers manifested itself in subclinical signs of cholestasis.Eksperimentalna istraživanja na životinjama pokazuju da kronična izloženost aluminiju može izazvati smanjen prijenos organskih aniona preko žučnih kanalića, što ima za posljedicu poremećaje sekrecije žuči i kolestazu. Učinci kronične izloženosti aluminiju na bilijarnu funkciju u ljudi do sada nisu istraživani. Procjenjivali smo učinke na bilijarnu funkciju radnika koji su profesionalno izloženi prašini i dimu aluminija. U izloženoj skupini bila su 34 muškarca, životne dobi (44,1±7,8) godina koji su tijekom (21,6±2,5) godina bili izloženi razini do 4,6 mg m-3 prašine i dima aluminija. Kontrolna skupina sastojala se od 30 neizloženih radnika. Vrijednosti aluminija određene su u serumu i mokraći u obje skupine prije i nakon davanja kelatirajućeg spoja (deferoksamin u dozi od 1 g im.). Za procjenu bilijarne funkcije rabljeni su ovi pokazatelji: γ-glutamil transpeptidaza, alkalna fosfataza, 5-nukleozidaza, kolesterol, ukupni i indirektni bilirubin te žučne kiseline. Analizirana je korelacija između izloženosti aluminiju i bilijarne funkcije. Srednja vrijednost Al u serumu izloženih radnika [(4,91±3,86) µg L-1], kao i koncentracije Al u mokraći prije [(1,57±1,93) µg L-1] i nakon primjene kelatirajućeg spoja [(11,5±15,0) µg L-1] bile su statistički značajno više u odnosu na vrijednosti u kontrolnih ispitanika. Vrijednosti ukupnog i indirektnoog bilirubina te alkalne fosfataze bile su statistički značajno više u izloženih radnika i pozitivno su korelirale s ukupnim Al izlučenim mokraćom nakon primjene kelatora. Može se zaključiti da kronična profesionalna izloženost prašini i dimu aluminija dovodi do tjelesnog opterećenja aluminijem i poremećaja bilijarne funkcije, što se odražava supkliničkim znakovima kolestaze

Nuclei, Superheavy Nuclei and Hypermatter in a chiral SU(3)-Modell

A model based on chiral SU(3)-symmetry in nonlinear realisation is used for the investigation of nuclei, superheavy nuclei, hypernuclei and multistrange nuclear objects (so called MEMOs). The model works very well in the case of nuclei and hypernuclei with one Lambda-particle and rules out MEMOs. Basic observables which are known for nuclei and hypernuclei are reproduced satisfactorily. The model predicts Z=120 and N=172, 184 and 198 as the next shell closures in the region of superheavy nuclei. The calculations have been performed in self-consistent relativistic mean field approximation assuming spherical symmetry. The parameters were adapted to known nuclei.Comment: 19 pages, 11 figure

Incorporating the geometry of dispersal and migration to understand spatial patterns of species distributions

Dispersal and migration can be important drivers of species distributions. Because the paths followed by individuals of many species are curvilinear, spatial statistical models based on rectilinear coordinates systems would fail to predict population connectivity or the ecological consequences of migration or species invasions. I propose that we view migration/dispersal as if organisms were moving along curvilinear geometrical objects called smooth manifolds. In that view, the curvilinear pathways become the ‘shortest realised paths’ arising from the necessity to minimise mortality risks and energy costs. One can then define curvilinear coordinate systems on such manifolds. I describe a procedure to incorporate manifolds and define appropriate coordinate systems, with focus on trajectories (1D manifolds), as parts of mechanistic ecological models. I show how a statistical method, known as ‘manifold learning’, enables one to define the manifold and the appropriate coordinate systems needed to calculate population connectivity or study the effects of migrations (e.g. in aquatic invertebrates, fish, insects and birds). This approach may help in the design of networks of protected areas, in studying the consequences of invasion, range expansions, or transfer of parasites/diseases. Overall, a geometrical view to animal movement gives a novel perspective to the understanding of the ecological role of dispersal and migration