New positive patch test reactions on day 7-The additional value of the day 7 patch test reading

Background: Not performing a day (D) 7 patch test reading might result in positive patch test reactions being missed. Objectives: To investigate the added value of the D7 patch test reading for individual allergens, and to identify patient characteristics and allergen groups associated with new positive D7 reactions. Methods: Data from patients patch tested between 2008 and 2018 with the extended European baseline series were analysed. Patch test readings were performed on D3 and D7. Positive reactions were categorized into positive on D3 or new positive on D7. Results: A total of 3292 patients were consecutively patch tested with at least 43 allergens of the TRUE Test panels 1 and 2 supplemented with investigator-loaded allergens. In total, 447 (13.6%) patients showed new positive D7 reactions. In univariable regression analysis, age between 18 and 30 years showed a negative association with new positive D7 reactions. Significantly more D7 positive reactions were seen for topicals (odds ratio [OR] 2.60, 95% confidence interval [CI]: 1.92-3.51) and corticosteroids (OR 1.87, 95% CI: 1.09-3.21). No associations were found between sex, atopic dermatitis and occupational dermatitis and a new positive D7 reaction. Conclusion: A D7 reading to identify new positive patch test reactions is of added value, especially for topicals and corticosteroids

Different crystal morphologies lead to slightly different conformations of light-harvesting complex II as monitored by variations of the intrinsic fluorescence lifetime

In 2005, it was found that the fluorescence of crystals of the major light-harvesting complex LHCII of green plants is significantly quenched when compared to the fluorescence of isolated LHCII (A. A. Pascal et al., Nature, 2005, 436, 134-137). The Raman spectrum of crystallized LHCII was also found to be different from that of isolated LHCII but very similar to that of aggregated LHCII, which has often been considered a good model system for studying nonphotochemical quenching (NPQ), the major protection mechanism of plants against photodamage in high light. It was proposed that in the crystal LHCII adopts a similar (quenching) conformation as during NPQ and indeed similar changes in the Raman spectrum were observed during NPQ in vivo (A. V. Ruban et al., Nature, 2007, 450, 575-579). We now compared the fluorescence of various types of crystals, differing in morphology and age. Each type gave rise to its own characteristic mono-exponential fluorescence lifetime, which was 5 to 10 times shorter than that of isolated LHCII. This indicates that fluorescence is not quenched by random impurities and packing defects (as proposed recently by T. Barros et al., EMBO Journal, 2009, 28, 298-306), but that LHCII adopts a particular structure in each crystal type, that leads to fluorescence quenching. Most interestingly, the extent of quenching appears to depend on the crystal morphology, indicating that also the crystal structure depends on this crystal morphology but at the moment no data are available to correlate the crystals' structural changes to changes in fluorescence lifetime

Complexity galore:3D cultures, biomechanics and systems medicine at the eighth ENBDC workshop "Methods in Mammary Gland Development and Cancer"

The ENBDC workshop “Methods in Mammary Gland Development and Cancer” is an established international forum to showcase the latest technical advances in the field. The eighth meeting focused on emerging concepts and technologies for studying normal and neoplastic breast development

Imagine beyond: recent breakthroughs and next challenges in mammary gland biology and breast cancer research

On 8 December 2022 the organizing committee of the European Network for Breast Development and Cancer labs (ENBDC) held its fifth annual Think Tank meeting in Amsterdam, the Netherlands. Here, we embraced the opportunity to look back to identify the most prominent breakthroughs of the past ten years and to reflect on the main challenges that lie ahead for our field in the years to come. The outcomes of these discussions are presented in this position paper, in the hope that it will serve as a summary of the current state of affairs in mammary gland biology and breast cancer research for early career researchers and other newcomers in the field, and as inspiration for scientists and clinicians to move the field forward

Severe CTE and TDP-43 pathology in a former professional soccer player with dementia: a clinicopathological case report and review of the literature

In the last decades, numerous post-mortem case series have documented chronic traumatic encephalopathy (CTE) in former contact-sport athletes, though reports of CTE pathology in former soccer players are scarce. This study presents a clinicopathological case of a former professional soccer player with young-onset dementia. The patient experienced early onset progressive cognitive decline and developed dementia in his mid-50 s, after playing soccer for 12 years at a professional level. While the clinical picture mimicked Alzheimer's disease, amyloid PET imaging did not provide evidence of elevated beta-amyloid plaque density. After he died in his mid-60 s, brain autopsy showed severe phosphorylated tau (p-tau) abnormalities fulfilling the neuropathological criteria for high-stage CTE, as well as astrocytic and oligodendroglial tau pathology in terms of tufted astrocytes, thorn-shaped astrocytes, and coiled bodies. Additionally, there were TAR DNA-binding protein 43 (TDP-43) positive cytoplasmic inclusions in the frontal lobe and hippocampus, and Amyloid Precursor Protein (APP) positivity in the axons of the white matter. A systematic review of the literature revealed only 13 other soccer players with postmortem diagnosis of CTE. Our report illustrates the complex clinicopathological correlation of CTE and the need for disease-specific biomarkers

Photoprotection in Plants Involves a Change in Lutein 1 Binding Domain in the Major Light-harvesting Complex of Photosystem II

Nonphotochemical quenching (NPQ) is the fundamental process by which plants exposed to high light intensities dissipate the potentially harmful excess energy as heat. Recently, it has been shown that efficient energy dissipation can be induced in the major light-harvesting complexes of photosystem II (LHCII) in the absence of protein-protein interactions. Spectroscopic measurements on these samples (LHCII gels) in the quenched state revealed specific alterations in the absorption and circular dichroism bands assigned to neoxanthin and lutein 1 molecules. In this work, we investigate the changes in conformation of the pigments involved in NPQ using resonance Raman spectroscopy. By selective excitation we show that, as well as the twisting of neoxanthin that has been reported previously, the lutein 1 pigment also undergoes a significant change in conformation when LHCII switches to the energy dissipative state. Selective two-photon excitation of carotenoid (Car) dark states (Car

Distinct Molecular Evolutionary Mechanisms Underlie the Functional Diversification of the Wnt and TGFβ Signaling Pathways

The canonical Wnt pathway is one of the oldest and most functionally diverse of animal intercellular signaling pathways. Though much is known about loss-of-function phenotypes for Wnt pathway components in several model organisms, the question of how this pathway achieved its current repertoire of functions has not been addressed. Our phylogenetic analyses of 11 multigene families from five species belonging to distinct phyla, as well as additional analyses employing the 12 Drosophila genomes, suggest frequent gene duplications affecting ligands and receptors as well as co-evolution of new ligand–receptor pairs likely facilitated the expansion of this pathway’s capabilities. Further, several examples of recent gene loss are visible in Drosophila when compared to family members in other phyla. By comparison the TGFβ signaling pathway is characterized by ancient gene duplications of ligands, receptors, and signal transducers with recent duplication events restricted to the vertebrate lineage. Overall, the data suggest that two distinct molecular evolutionary mechanisms can create a functionally diverse developmental signaling pathway. These are the recent dynamic generation of new genes and ligand–receptor interactions as seen in the Wnt pathway and the conservative adaptation of ancient pre-existing genes to new roles as seen in the TGFβ pathway. From a practical perspective, the former mechanism limits the investigator’s ability to transfer knowledge of specific pathway functions across species while the latter facilitates knowledge transfer

WNT signalling in prostate cancer

Genome sequencing and gene expression analyses of prostate tumours have highlighted the potential importance of genetic and epigenetic changes observed in WNT signalling pathway components in prostate tumours-particularly in the development of castration-resistant prostate cancer. WNT signalling is also important in the prostate tumour microenvironment, in which WNT proteins secreted by the tumour stroma promote resistance to therapy, and in prostate cancer stem or progenitor cells, in which WNT-β-catenin signals promote self-renewal or expansion. Preclinical studies have demonstrated the potential of inhibitors that target WNT receptor complexes at the cell membrane or that block the interaction of β-catenin with lymphoid enhancer-binding factor 1 and the androgen receptor, in preventing prostate cancer progression. Some WNT signalling inhibitors are in phase I trials, but they have yet to be tested in patients with prostate cancer

VW Hyi: optical spectroscopy and Doppler tomography

We present high quality optical spectroscopy of the SU UMa-subtype dwarf nova, VW Hyi taken while the system was in quiescence. An S-wave is executed by the emission cores of the Hydrogen Balmer lines and by the emission lines of He I, Ca II, Fe II and He II. Using Doppler tomography we show it originates in the accretion stream-disc impact region. The He II emission is strongly phase-dependent, suggesting it originates exclusively within a hot cavity at the initial impact. We map the ionization structure of the stream-disc interaction region. One possible interpretation of this is that the Balmer hotspot lies downstream of the He II hotspot in the outer accretion disc, with the He I and Ca II hotspots at intermediate locations between the two. This suggests that Balmer emission is suppressed until material has cooled somewhat downstream of the impact site and is able to recombine. We favour a phase offset of 0.15+/-0.04 between the photometric ephemeris and inferior conjunction of the mass donor. The white dwarf contributes significantly to the optical continuum, with broad Balmer absorption and narrow Mg II 4481 absorption clearly apparent. This latter feature yields the gravitational redshift: v_grav=38+/-21 km s^-1, so M_1=0.71+0.18-0.26 M_sun. This implies M_2=0.11 +/- 0.03 M_sun and hence the donor is not a brown dwarf. A prominent Balmer jump is also observed. We note that the previously accepted system parameters for both VW Hyi and WX Hyi incoporate an algebraic error, and we provide a recalculated M_1(q) plane for WX Hyi.Comment: 10 pages (mn2e LaTeX), 9 figures, Accepted for publication in Monthly Notices of the Royal Astronomical Societ