A novel cellular pathway of antigen presentation and CD4 T cell activation in vivo

Dendritic cell activation of CD4 T cells in the lymph node draining a site of infection or vaccination is widely considered the central event in initiating adaptive immunity. The accepted dogma is that this occurs by stimulating local activation and antigen acquisition by dendritic cells, with subsequent lymph node migration, however the generalizability of this mechanism is unclear. Here we show that in some circumstances antigen can bypass the injection site inflammatory response, draining freely and rapidly to the lymph nodes where it interacts with subcapsular sinus (SCS) macrophages resulting in their death. Debris from these dying SCS macrophages is internalized by monocytes recruited from the circulation. This coordinated response leads to antigen presentation by monocytes and interactions with naïve CD4 T cells that can drive the initiation of T cell and B cell responses. These studies demonstrate an entirely novel pathway leading to initiation of adaptive immune responses in vivo

Anthropometric correlates of human anger

This is the post-print version of the final paper published in Evolution and Human Behavior. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2012 Elsevier B.V.The recalibrational theory of human anger predicts positive correlations between aggressive formidability and anger levels in males, and between physical attractiveness and anger levels in females. We tested these predictions by using a three-dimensional body scanner to collect anthropometric data about male aggressive formidability (measures of upper body muscularity and leg–body ratio) and female bodily attractiveness (waist–hip ratio, body mass index, overall body shape femininity, and several other measures). Predictions were partially supported: in males, two of three anger measures correlated significantly positively with several muscularity measures; in females, self-perceived attractiveness correlated significantly positively with two anger measures. However, most of these significant results were observed only after excluding from the sample 27 participants who were older than undergraduate age, leaving a subsample of 40 males and 51 females. Evidence for relationships between anthropometric attractiveness indicators and anger measures was weak, but there was some evidence for relationships between anthropometric attractiveness indicators and self-perceived attractiveness measures. While our results support the recalibrational theory's prediction that anger usage and formidability are positively correlated in males and suggest that this formidability can be assessed via anthropometric measures alone, they also suggest that this prediction may not apply to populations older than undergraduate age. Further, our results suggest that while female anger levels relate positively to self-perceived attractiveness, they are unrelated to most anthropometric measures of bodily attractiveness

Impact of straight to test pathways on time to diagnosis in oesophageal and gastric cancer

Background: Cancer survival in the UK has doubled in the last 40 years; however, 1-year and 5-year survival rates are still lower than other countries. One cause may be a delay between referral into secondary care and subsequent investigation. We set out to evaluate the impact of a straight to test pathway (STTP) on time to diagnosis for upper gastrointestinal (UGI) cancer.Methods: Six hospital Trusts across the East Midlands Clinical Network introduced a STTP enabling general practitioners to refer patients with suspected UGI cancer (oesophageal/gastric) for immediate investigation, without the need to see a hospital specialist first. Data were collected for all patients referred between 2013 and 2015 with suspected UGI cancer and stratified by STTP or traditional referral pathway. Overall time from referral to diagnosis was compared. Data from two Trusts who did not implement STTP acted as control.Results: 340 patients followed the STTP pathway and 495 followed the traditional route. STTP saved a mean of 7 days from referral to treatment (with a 95% CI of 3 to 11 days,

Muscularity and attractiveness as predictors of human egalitarianism

This is the post-print version of the final paper published in Personality and Individual Differences. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2010 Elsevier B.V.In ancestral human environments, muscularity and height (in males) and physical attractiveness (in both sexes) would theoretically have correlated positively with one’s social status, and thus with one’s ability to benefit from social inequality. We therefore hypothesized that individuals who are more characterized by these traits would be less egalitarian (i.e., less likely to believe that resources should be distributed equally in social groups). We used a white-light 3D body scanner to extract anthropometric measurements from 118 participants, and our four egalitarianism measures included social dominance orientation and social value orientation. We found that as hypothesized, muscularity and waist–chest ratio in males, and self-perceived attractiveness in both sexes, tended to associate significantly in the predicted directions with the four egalitarianism measures; most of these correlations were of medium size. Neither height, nor two anthropometrically-assessed attractiveness measures (volume height index and waist–hip ratio), associated significantly with any egalitarianism measure in either sex. Egalitarianism has crucial social repercussions (e.g., taxes, welfare and civil rights), and results from the current study shed light on its origins

Developing a xenograft model of human vasculature in the mouse ear pinna

Humanised xenograft models allow for the analysis of human tissue within a physiological environment in vivo. However, current models often rely on the angiogenesis and ingrowth of recipient vasculature to perfuse tissues, preventing analysis of biological processes and diseases involving human blood vessels. This limits the effectiveness of xenografts in replicating human physiology and may lead to issues with translating findings into human research. We have designed a xenograft model of human vasculature to address this issue. Human subcutaneous fat was cultured in vitro to promote blood vessel outgrowth prior to implantation into immunocompromised mice. We demonstrate that implants survived, retained human vasculature and anastomosed with the circulatory system of the recipient mouse. Significantly, by performing transplants into the ear pinna, this system enabled intravital observation of xenografts by multiphoton microscopy, allowing us to visualise the steps leading to vascular cytoadherence of erythrocytes infected with the human parasite Plasmodium falciparum. This model represents a useful tool for imaging the interactions that occur within human tissues in vivo and permits visualization of blood flow and cellular recruitment in a system which is amenable to intervention for various studies in basic biology together with drug evaluation and mechanism of action studies

Glial wingless/Wnt regulates glutamate receptor clustering and synaptic physiology at the Drosophila neuromuscular junction

Glial cells are emerging as important regulators of synapse formation, maturation, and plasticity through the release of secreted signaling molecules. Here we use chromatin immunoprecipitation along with Drosophila genomic tiling arrays to define potential targets of the glial transcription factor Reversed polarity (Repo). Unexpectedly, we identified wingless (wg), a secreted morphogen that regulates synaptic growth at the Drosophila larval neuromuscular junction (NMJ), as a potential Repo target gene. We demonstrate that Repo regulates wg expression in vivo and that local glial cells secrete Wg at the NMJ to regulate glutamate receptor clustering and synaptic function. This work identifies Wg as a novel in vivo glial-secreted factor that specifically modulates assembly of the postsynaptic signaling machinery at the Drosophila NMJ

1934: Abilene Christian College Bible Lectures - Full Text

INTRODUCTION The theme for the Lectures for 1934, “The New Testament Church in History,” is a very timely one and follows naturally the theme of the 1933 Lectures, “The Church We Read About in the New Testament.” There is no subject that is so vital in our work as Christians today as a proper understanding of the great spiritual kingdom of our Savior, the church which was built by Jesus Christ. It is a hard lesson to teach because all people are so dull of hearing concerning things spiritual. Just as Nicodemus marveled when the Christ told him of the spiritual kingdom so do people today wonder and marvel when they are told that there is only one great church, the spiritual kingdom of our Lord and Savior Jesus Christ, and that all the saved of earth belong to that church and that belonging to anything else profits little, and is unnecessary. Not only are numbers of denominational churches and people who have no religious affiliation ignorant of the true meaning of the church, but even those who claim to be members of the one body are lacking in understanding concerning the kingdom of Christ. It is therefore the purpose of the Abilene College Lectures last year, this year and next year to arouse a greater interest in the study and the teaching of this very vital matter. In this particular volume much valuable information is brought together on the trials and struggles of the church from its foundations to the present. The speakers have made careful preparation on their subjects and have given lessons that should prove helpful to all who desire to have a better understanding of the church. Our prayer is that these Lectures may be read by many and that they may do much good in the name of the Christ. Jas. F. Cox,President, Abilene Christian College. Nov. 6, 1934

Assessment of murine collagen-induced arthritis by longitudinal non-invasive duplexed molecular optical imaging

In the present study we evaluated the use of four commercially available fluorescent probes to monitor disease activity in murine CIA and its suppression during glucocorticoid therapy.  Arthritis was induced in male DBA/1 mice by immunization with type II collagen in Complete Freund's Adjuvant, followed by a boost of collagen in PBS. Four fluorescent probes from PerkinElmer in combination [ProSense 750 fluorescent activatable sensor technology (FAST) with Neutrophil Elastase 680 FAST and MMPSense 750 FAST with CatK 680 FAST] were used to monitor disease development from day 5 through to day 40 post-immunization. Fluorescence generated in vivo by the probes was correlated with clinical and histological score and paw measurements.  The fluorescence intensity emitted by each probe was shown to correlate with the conventional measurements of disease. The highest degree of correlation was observed with ProSense 750 FAST in combination with Neutrophil Elastase 680 FAST; these probes were then used to successfully assess CIA suppression during dexamethasone treatment.  We have demonstrated that longitudinal non-invasive duplexed optical fluorescence imaging provides a simple assessment of arthritic disease activity within the joints of mice following the induction of CIA and may represent a powerful tool to monitor the efficacy of drug treatments in preclinical studies

Identification of a novel type of spacer element required for imprinting in fission yeast

Asymmetrical segregation of differentiated sister chromatids is thought to be important for cellular differentiation in higher eukaryotes. Similarly, in fission yeast, cellular differentiation involves the asymmetrical segregation of a chromosomal imprint. This imprint has been shown to consist of two ribonucleotides that are incorporated into the DNA during laggingstrand synthesis in response to a replication pause, but the underlying mechanism remains unknown. Here we present key novel discoveries important for unravelling this process. Our data show that cis-acting sequences within the mat1 cassette mediate pausing of replication forks at the proximity of the imprinting site, and the results suggest that this pause dictates specific priming at the position of imprinting in a sequence-independent manner. Also, we identify a novel type of cis-acting spacer region important for the imprinting process that affects where subsequent primers are put down after the replication fork is released from the pause. Thus, our data suggest that the imprint is formed by ligation of a not-fullyprocessed Okazaki fragment to the subsequent fragment. The presented work addresses how differentiated sister chromatids are established during DNA replication through the involvement of replication barriers