Beyond altruism: British football and charity, 1877-1914

Football charity matches and tournaments played a significant part in the development of the sport in Britain, overlapping the era of friendly games and the advent of competitive leagues. The football community prided itself on its contributions to charity, raising more money than any other sport before 1914, and stakeholders within the game – associations, clubs, players and patrons – gained considerable kudos for this perceived altruism. However, this paper will demonstrate that amounts donated, though welcome, were relatively minor sources of revenue for both institutions and individuals, and that the charity match became less important to clubs in a professional, and increasingly commercial, era

Programmable in situ amplification for multiplexed imaging of mRNA expression

In situ hybridization methods enable the mapping of mRNA expression within intact biological samples. With current approaches, it is challenging to simultaneously map multiple target mRNAs within whole-mount vertebrate embryos, representing a significant limitation in attempting to study interacting regulatory elements in systems most relevant to human development and disease. Here, we report a multiplexed fluorescent in situ hybridization method based on orthogonal amplification with hybridization chain reactions (HCR). With this approach, RNA probes complementary to mRNA targets trigger chain reactions in which fluorophore-labeled RNA hairpins self-assemble into tethered fluorescent amplification polymers. The programmability and sequence specificity of these amplification cascades enable multiple HCR amplifiers to operate orthogonally at the same time in the same sample. Robust performance is achieved when imaging five target mRNAs simultaneously in fixed whole-mount and sectioned zebrafish embryos. HCR amplifiers exhibit deep sample penetration, high signal-to-background ratios and sharp signal localization

Variants in autophagy-related genes and clinical characteristics in melanoma: a population-based study

Autophagy has been linked with melanoma risk and survival, but no polymorphisms in autophagy-related (ATG) genes have been investigated in relation to melanoma progression. We examined five single-nucleotide polymorphisms (SNPs) in three ATG genes (ATG5; ATG10; and ATG16L) with known or suspected impact on autophagic flux in an international population-based case-control study of melanoma. DNA from 911 melanoma patients was genotyped. An association was identified between (GG) (rs2241880) and earlier stage at diagnosis (OR 0.47; 95% Confidence Intervals (CI) = 0.27-0.81, P = 0.02) and a decrease in Breslow thickness (P = 0.03). The ATG16L heterozygous genotype (AG) (rs2241880) was associated with younger age at diagnosis (P = 0.02). Two SNPs in ATG5 were found to be associated with increased stage (rs2245214 CG, OR 1.47; 95% CI = 1.11-1.94, P = 0.03; rs510432 CC, OR 1.84; 95% CI = 1.12-3.02, P = 0.05). Finally, we identified inverse associations between ATG5 (GG rs2245214) and melanomas on the scalp or neck (OR 0.20, 95% CI = 0.05-0.86, P = 0.03); ATG10 (CC) (rs1864182) and brisk tumor infiltrating lymphocytes (TILs) (OR 0.42; 95% CI = 0.21-0.88, P = 0.02), and ATG5 (CC) (rs510432) with nonbrisk TILs (OR 0.55; 95% CI = 0.34-0.87, P = 0.01). Our data suggest that ATG SNPs might be differentially associated with specific host and tumor characteristics including age at diagnosis, TILs, and stage. These associations may be critical to understanding the role of autophagy in cancer, and further investigation will help characterize the contribution of these variants to melanoma progression

Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology

Supported by the Office of International Affairs, National Cancer Institute (NCI), the "US-Japan Workshop on Immunological Biomarkers in Oncology" was held in March 2009. The workshop was related to a task force launched by the International Society for the Biological Therapy of Cancer (iSBTc) and the United States Food and Drug Administration (FDA) to identify strategies for biomarker discovery and validation in the field of biotherapy. The effort will culminate on October 28th 2009 in the "iSBTc-FDA-NCI Workshop on Prognostic and Predictive Immunologic Biomarkers in Cancer", which will be held in Washington DC in association with the Annual Meeting. The purposes of the US-Japan workshop were a) to discuss novel approaches to enhance the discovery of predictive and/or prognostic markers in cancer immunotherapy; b) to define the state of the science in biomarker discovery and validation. The participation of Japanese and US scientists provided the opportunity to identify shared or discordant themes across the distinct immune genetic background and the diverse prevalence of disease between the two Nations

In situ hybridization method for localization of mRNA molecules in medicago tissue sections

Here we describe an in situ hybridization (ISH) method using Invitrogen™ ViewRNA™ ISH Tissue Assay (ThermoFisher Scientific) optimized for Medicago root and nodules sections. The method is based on branched (b)DNA signal amplification technology originally developed for use in microplate format and further adapted for detection of (m)RNAs in mammalian tissue sections. Signal amplification is achieved via a series of sequential hybridizations of linking sequences which are anchored to complementary sequences present on specific oligonucleotide probes. The typical (m)RNA probe set contains ~20 synthetic adjacent oligonucleotide pairs. Each probe is composed of a 20bp primary sequence designed to target sequence of interest and a secondary extended sequence serving as a template for hybridization of a preamplifier oligonucleotide. The preamplifier forms a stable hybrid only if it hybridizes to two adjacent probes. By this principle, background is reduced. Other regions on the preamplifier are designed to hybridize to multiple bDNA amplifier molecules that create a branched structure. Finally, alkaline phosphatase (AP)-labeled oligonucleotides, which are complementary to bDNA amplifier sequences, bind to the bDNA molecule by hybridization. By adding Fast Red substrate, red punctuated precipitates are formed that can be detected by light bright and/or fluorescent microscope. ThermoFisher Scientific (https://www.thermofisher.com/nl/en/home.html) designs and synthesizes probe sets for a gene of interest and Invitrogen™ ViewRNA™ ISH Tissue Assay kits include all components required for pretreatment of plant tissues, hybridization and signal amplification.</p