Radiation inactivation analysis of amino acid transport systems in Neurospora crassa

Radiation inactivation analysis of amino acid transport systems in Neurospora crass

Electronic Energy Transfer to the S2 Level of the Acceptor in Functionalised Boron Dipyrromethene Dyes

Taking the high road: Highly efficient electronic energy transfer takes place from a set of appended aryl polycyclic hydrocarbons to an expanded boron dipyrromethene (Bodipy)-based dye (see figure) despite negligible spectral overlap with the lowest-energy excited state localised on the acceptor.A multi-component array has been constructed around an expanded boron dipyrromethene (Bodipy) dye that absorbs and emits in the far-red region. One of the appendages is a perylene-based moiety that is connected to the boron atom of the terminal Bodipy by a 1,4-diethynylphenylene connector. Despite the fact that there is almost negligible spectral overlap between fluorescence from the perylene unit and absorption by the Bodipy residue, electronic energy transfer is rapid and essentially quantitative. It is concluded that at least half of the photons absorbed by perylene are transferred to the upper-lying singlet excited state (S2) associated with the Bodipy-based acceptor. The second appendage is a pyrene unit that is covalently linked to fluorene, through an ethynylene spacer, and to the boron atom of the Bodipy terminus, through a 1,4-diethynylphenylene connector. Pyrene absorbs and emits at higher energy than perylene and there is strong spectral overlap with the Bodipy-based S2 state, and none with the corresponding S1 state. Electronic energy transfer is now very fast and exclusively to the S2 state of the acceptor. It is difficult to compute reasonable estimates for the rates of Coulombic energy transfer, because of uncertainties in the orientation factor, but the principle mechanism is believed to arise from electron exchange. Comparison with an earlier array built around a conventional Bodipy dye indicates that there are comparable electronic coupling matrix elements for the two systems. It is notable that pyrene is more strongly coupled to the Bodipy unit than perylene in both arrays. These new arrays function as highly effective solar concentrators

‘I actually know that things will get better’:The many pathways to resilience of LGBTQIA+ youth in out-of-home care

Research on the lives of lesbian, gay, bisexual, transgender, queer, intersex, asexual and other forms of sexual identities and orientations (LGBTQIA+) youth in care has mainly examined their experiences from a risk-based approach, while few studies have explored their resilience experiences. Using in-depth interviews, the present study aims to illuminate the resilience experiences of 13 LGBTQIA+ young people in out-of-home care in the Netherlands. Four themes emerged from their narratives: relationships that support and empower; construction of a positive identity around their sexual orientation and gender identity and expression (SOGIE); community involvement and self-relying strategies. Our findings support the view of resilience as a complex process that shows at an individual, interpersonal and social level

The relationship between members of the canonical NF-κB pathway, components of tumour microenvironment and survival in patients with invasive ductal breast cancer

The aim of the present study was to examine the relationship between tumour NF-κB activation, tumour microenvironment including local inflammatory response (LIR) and cancer-specific survival in patients with operable ductal breast cancer. Immunohistochemistry (tissue microarray of 376 patients) and western blotting (MCF7 and MDA-MB-231 breast cancer cells) was performed to assess expression of key members of the canonical NF-κB pathway (inhibitory kappa B kinase (IKKβ) and phosphorylated p65 Ser-536 (p-p65)). Following silencing of IKKβ, cell viability and apoptosis was assessed in both MCF7 and MDA-MB-231 cell lines. P-p65 was associated with cancer-specific survival (CSS) (nuclear P=0.042 and total P=0.025). High total p-p65 was associated with increase grade tumour grade (P=0.010), ER positivity (P=0.023), molecular subtype (P=0.005), lower Klintrup- Makinen grade (P=0.013) and decreased CD138 count (P=0.032). On multivariate analysis, total p-p65 expression independently associated with poorer CSS (P=0.020). In vitro work demonstrated that the canonical NF-κB pathway was inducible by exposure to TNFα in ER-positive MCF7 cells and to a lesser extent in ER-negative MDAMB- 231 cells. Reduction of IKKβ expression by siRNA transfection increased levels of apoptosis and reduced cell viability in both MCF7 (P= 0.001, P=0.002, respectively). This is consistent with the hypothesis that canonical IKKβ-NF-κB signalling drives tumour survival. These results suggest that activation of the canonical NF-κB pathway is an important determinant of poor outcome in patients with invasive ductal breast cancer

Genetic background influences tumour development in heterozygous Men1 knockout mice

Multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder caused by MEN1 germline mutations, is characterised by parathyroid, pancreatic and pituitary tumours. MEN1 mutations also cause familial isolated primary hyperparathyroidism (FIHP), a milder condition causing hyperparathyroidism only. Identical mutations can cause either MEN1 or FIHP in different families, thereby implicating a role for genetic modifiers in altering phenotypic expression of tumours. We therefore investigated the effects of genetic background and potential for genetic modifiers on tumour development in adult Men1+/- mice, which develop tumours of the parathyroids, pancreatic islets, anterior pituitary, adrenal cortex and gonads, that had been backcrossed to generate C57BL/6 and 129S6/SvEv congenic strains. A total of 275 Men1+/- mice, aged 5–26 months were macroscopically studied, and this revealed that genetic background significantly influenced the development of pituitary, adrenal and ovarian tumours, which occurred in mice over 12 months of age and more frequently in C57BL/6 females, 129S6/SvEv males and 129S6/SvEv females, respectively. Moreover, pituitary and adrenal tumours developed earlier, in C57BL/6 males and 129S6/SvEv females, respectively, and pancreatic and testicular tumours developed earlier in 129S6/SvEv males. Furthermore, glucagon-positive staining pancreatic tumours occurred more frequently in 129S6/SvEv Men1+/- mice. Whole genome sequence analysis of 129S6/SvEv and C57BL/6 Men1+/- mice revealed >54,000 different variants in >300 genes. These included, Coq7, Dmpk, Ccne2, Kras, Wnt2b, Il3ra and Tnfrsf10a, and qRT-PCR analysis revealed that Kras was significantly higher in pituitaries of male 129S6/SvEv mice. Thus, our results demonstrate that Kras and other genes could represent possible genetic modifiers of Men1

Yours ever (well, maybe): Studies and signposts in letter writing

Electronic mail and other digital communications technologies seemingly threaten to end the era of handwritten and typed letters, now affectionately seen as part of snail mail. In this essay, I analyze a group of popular and scholarly studies about letter writing-including examples of pundits critiquing the use of e-mail, etiquette manuals advising why the handwritten letter still possesses value, historians and literary scholars studying the role of letters in the past and what it tells us about our present attitudes about digital communications technologies, and futurists predicting how we will function as personal archivists maintaining every document including e-mail. These are useful guideposts for archivists, providing both a sense of the present and the past in the role, value and nature of letters and their successors. They also provide insights into how such documents should be studied, expanding our gaze beyond the particular letters, to the tools used to create them and the traditions dictating their form and function. We also can discern a role for archivists, both for contributing to the literature about documents and in using these studies and commentaries, suggesting not a new disciplinary realm but opportunities for new interdisciplinary work. Examining a documentary form makes us more sensitive to both the innovations and traditions as it shifts from the analog to the digital; we can learn not to be caught up in hysteria or nostalgia about one form over another and archivists can learn about what they might expect in their labors to document society and its institutions. At one time, paper was part of an innovative technology, with roles very similar to the Internet and e-mail today. It may be that the shifts are far less revolutionary than is often assumed. Reading such works also suggests, finally, that archivists ought to rethink how they view their own knowledge and how it is constructed and used. © 2010 Springer Science+Business Media B.V