Insights from computational modeling in inflammation and acute rejection in limb transplantation

Acute skin rejection in vascularized composite allotransplantation (VCA) is the major obstacle for wider adoption in clinical practice. This study utilized computational modeling to identify biomarkers for diagnosis and targets for treatment of skin rejection. Protein levels of 14 inflammatory mediators in skin and muscle biopsies from syngeneic grafts [n = 10], allogeneic transplants without immunosuppression [n = 10] and allografts treated with tacrolimus [n = 10] were assessed by multiplexed analysis technology. Hierarchical Clustering Analysis, Principal Component Analysis, Random Forest Classification and Multinomial Logistic Regression models were used to segregate experimental groups. Based on Random Forest Classification, Multinomial Logistic Regression and Hierarchical Clustering Analysis models, IL-4, TNF-α and IL-12p70 were the best predictors of skin rejection and identified rejection well in advance of histopathological alterations. TNF-α and IL-12p70 were the best predictors of muscle rejection and also preceded histopathological alterations. Principal Component Analysis identified IL-1α, IL-18, IL-1β, and IL-4 as principal drivers of transplant rejection. Thus, inflammatory patterns associated with rejection are specific for the individual tissue and may be superior for early detection and targeted treatment of rejection. © 2014 Wolfram et al

Mutualism in museums: A model for engaging undergraduates in biodiversity science

<div><p>Museums have an untapped potential to engage students in hands-on learning. Here, we describe the development of a tiered museum-based program at the University of California, Berkeley as a model for engaging undergraduates in biodiversity science. This decade-long effort to increase student participation in collections demonstrates the mutual benefits of undergraduate involvement. Museums benefit from critical help in collections care and an increased intellectual vitality, while students simultaneously gain essential research skills and an unparalleled exposure to biodiversity. Five first steps to creating a program are: dedicate a coordinator, offer credit, diversify participation, create a tiered structure, and build community.</p></div

Tiered structure.

<p>The stepwise progression of the MVZ Undergraduate Program allows students with no previous experience (e.g., “Open to All” and “Beginner”) to join the MVZ and then advance to more complex positions (e.g., “Intermediate” and “Advanced”) as they gain experience. Advanced students also give back to the program by helping to recruit and train new students. MVZ, Museum of Vertebrate Zoology.</p

Scientific benefits to the museum.

<p>Summary of MVZ curatorial activities performed by undergraduates, both paid and work-for-credit, and their collective output over 10 years (1 June 2005 to 31 May 2015). Because the museum’s specimen data are freely available online (<a href="http://arctosdb.org" target="_blank">http://arctosdb.org</a>, <a href="http://vertnet.org" target="_blank">http://vertnet.org</a>, <a href="http://gbif.org" target="_blank">http://gbif.org</a>, <a href="http://www.idigbio.org" target="_blank">http://www.idigbio.org</a>), these student efforts benefit not just the museum but also the broader scientific community. Data collection details are available in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2003318#pbio.2003318.s003" target="_blank">S1 Text</a>.</p

Undergraduates engaged in active-learning.

<p><b>(A)</b> Members of the MVZ Undergraduate Program involved in curatorial and specimen preparation activities. Clockwise from top left: georeferencing specimen localities, cleaning skeletal material, cataloging bird specimens, and topping off ethanol in jars of fluid specimens. <b>(B)</b> Members of the MVZ Undergraduate Program involved in museum-based research projects. Clockwise from top left: presenting research at a conference, collecting herpetological specimens in the Sierra Nevada, analyzing digital recordings of bird songs, and conducting molecular research in the Evolutionary Genetics Lab. MVZ, Museum of Vertebrate Zoology.</p

Search for high-energy neutrinos from gravitational wave event GW151226 and candidate LVT151012 with ANTARES and IceCube

The Advanced LIGO observatories detected gravitational waves from two binary black hole mergers during their first observation run (O1). We present a high-energy neutrino follow-up search for the second gravitational wave event, GW151226, as well as for gravitational wave candidate LVT151012. We find two and four neutrino candidates detected by IceCube, and one and zero detected by Antares, within �500s around the respective gravitational wave signals, consistent with the expected background rate. None of these neutrino candidates are found to be directionally coincident with GW151226 or LVT151012. We use nondetection to constrain isotropic-equivalent high-energy neutrino emission from GW151226, adopting the GW event�s 3D localization, to less than 2�10^51�2�10^54??ergby Anand Sengupta et al

SARS-CoV-2 lineage dynamics in England from September to November 2021: high diversity of Delta sub-lineages and increased transmissibility of AY.4.2

Abstract Background Since the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Genomic surveillance in regions of high immunity is crucial in detecting emerging variants that can more successfully navigate the immune landscape. Methods We present phylogenetic relationships and lineage dynamics within England (a country with high levels of immunity), as inferred from a random community sample of individuals who provided a self-administered throat and nose swab for rt-PCR testing as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. During round 14 (9 September–27 September 2021) and 15 (19 October–5 November 2021) lineages were determined for 1322 positive individuals, with 27.1% of those which reported their symptom status reporting no symptoms in the previous month. Results We identified 44 unique lineages, all of which were Delta or Delta sub-lineages, and found a reduction in their mutation rate over the study period. The proportion of the Delta sub-lineage AY.4.2 was increasing, with a reproduction number 15% (95% CI 8–23%) greater than the most prevalent lineage, AY.4. Further, AY.4.2 was less associated with the most predictive COVID-19 symptoms (p = 0.029) and had a reduced mutation rate (p = 0.050). Both AY.4.2 and AY.4 were found to be geographically clustered in September but this was no longer the case by late October/early November, with only the lineage AY.6 exhibiting clustering towards the South of England. Conclusions As SARS-CoV-2 moves towards endemicity and new variants emerge, genomic data obtained from random community samples can augment routine surveillance data without the potential biases introduced due to higher sampling rates of symptomatic individuals. </jats:sec