Toward integrated historical climate research: the example of Atmospheric Circulation Reconstructions over the Earth

Climate change has become a key environmental narrative of the 21st century. However, emphasis on the science of climate change has overshadowed studies focusing on human interpretations of climate history, of adaptation and resilience, and of explorations of the institutions and cultural coping strategies that may have helped people adapt to climate changes in the past. Moreover, although the idea of climate change has been subject to considerable scrutiny by the physical sciences, recent climate scholarship has highlighted the need for a re examination of the cultural and spatial dimensions of climate, with contributions from the humanities and social sciences. Establishing a multidisciplinary dialogue and approach to climate research past, present, and future has arguably never been more important. This article outlines developments in historical climatology research and considers examples of integrated multidisciplinary approaches to climate, climatic variability, and climate change research, conducted across the physical sciences, social sciences, humanities, and the arts. We highlight the international Atmospheric Circulation Reconstructions over the Earth (ACRE) initiative as one example of such an integrated approach. Initially, ACRE began as a response from climate science to the needs of the agricultural sector in Queensland, Australia for a longer, more spatially, and temporally-complete database of the weather. ACRE has now evolved to embrace an international group of researchers working together across disciplines to integrate their efforts into a four-dimensional (4D) dynamical global historical climate-quality reanalysis (reconstruction). WIREs Clim Change 2016, 7:164–174. doi:10.1002/wcc.37

What's in a virus? Folk understandings of hepatitis C infection and infectiousness among injecting drug users in Kings Cross, Sydney

BACKGROUND: To explore folk understandings of blood borne virus infection and infectiousness among injecting drug users in Kings Cross, Sydney. METHODS: Observational fieldwork was conducted in Kings Cross over a four month period. In-depth interviews with 24 current injectors and 4 key informants recruited from King Cross were undertaken. RESULTS: Hepatitis C (HCV) generated different meanings from HIV. HIV was considered "the dreaded" and generated fear of infection and dire disease progression. Whereas HCV was considered non-desirable but less threatening than HIV. The risks of transmitting HCV through sharing injecting paraphernalia was poorly understood. Some believed HCV infection was linked to poor hygiene and dirty water. Jaundice was mistakenly thought to indicate HCV infection and was used to gauge infectiousness. Many were confused about their current hepatitis C serostatus. Some participants thought they had a "dormant antibody" or that they had a "mild case" of infection. Participants were unsure what this meant for their own health or for their potential to infect others. CONCLUSION: Participants displayed confusion about transmission risks for hepatitis C, conflating blood awareness and hygiene health promotion messages. Participants' reliance on the symptom of jaundice to gauge serostatus places them at risk of transmitting and contracting HCV. Participants were confused about what a positive HCV diagnosis meant for their own health and their ability to infect others. Education is needed to debunk misconceptions about jaundice and clarify medical terms such as 'antibody' at the time of diagnosis. Further clarification of messages about injecting hygiene and blood awareness are also required

Transmission pathways for sporadic Shiga-toxin producing E. coli infections: A systematic review and meta-analysis

Background: Shiga-toxin E. coli infections remain a public health concern because of the severity of the gastrointestinal illness and associated complications. Transmission pathways are typically elucidated from outbreaks, with foodborne transmission the primary source. However, most STEC cases are sporadic. This systematic review aimed to identify the most common pathways for sporadic STEC transmission and quantify their importance. Methods: We systematically reviewed epidemiological studies of sporadic (non-outbreak) STEC cases that investigated potential risk factors. Searches were run in Medline, EMBASE, and Scopus. Included studies needed to confirm STEC infection and investigate ≥20 cases. Results: 31 studies were included, of which 25 were case-control or case-case studies. 62.5% found consumption of undercooked/raw meat associated with STEC infection while 70.4% found contact with animals or their environment a risk factor. Random-effects meta-analysis provided pooled odds ratios and population attributable fraction (PAF). The PAF was 19% for undercooked/raw meat, followed by person to person transmission at 15%. Contact with animals and visiting farm environments had PAFs of 14% and 12% respectively. Conclusions: Out of potential sources for STEC exposure, undercooked meat and contact with animals and their environment were the most frequently found transmission routes. Decreasing the chances of acquiring the bacteria by these methods would additionally cut down on the other major transmission route, person-to-person spread

Multiple roles of GluN2B-containing NMDA receptors in synaptic plasticity in juvenile hippocampus

AbstractIn the CA1 area of the hippocampus N-methyl-d-aspartate receptors (NMDARs) mediate the induction of long-term depression (LTD), short-term potentiation (STP) and long-term potentiation (LTP). All of these forms of synaptic plasticity can be readily studied in juvenile hippocampal slices but the involvement of particular NMDAR subunits in the induction of these different forms of synaptic plasticity is currently unclear. Here, using NVP-AAM077, Ro 25-6981 and UBP145 to target GluN2A-, 2B- and 2D-containing NMDARs respectively, we show that GluN2B-containing NMDARs (GluN2B) are involved in the induction of LTD, STP and LTP in slices prepared from P14 rat hippocampus. A concentration of Ro (1 μM) that selectively blocks GluN2B-containing diheteromers is able to block LTD. It also inhibits a component of STP without affecting LTP. A higher concentration of Ro (10 μM), that also inhibits GluN2A/B triheteromers, blocks LTP. UBP145 selectively inhibits the Ro-sensitive component of STP whereas NVP inhibits LTP. These data are consistent with a role of GluN2B diheretomers in LTD, a role of both GluN2B- and GluN2D- containing NMDARs in STP and a role of GluN2A/B triheteromers in LTP.This article is part of the Special Issue entitled ‘Ionotropic glutamate receptors’

Draxin acts as a molecular rheostat of canonical Wnt signaling to control cranial neural crest EMT

Neural crest cells undergo a spatiotemporally regulated epithelial-to-mesenchymal transition (EMT) that proceeds head to tailward to exit from the neural tube. In this study, we show that the secreted molecule Draxin is expressed in a transient rostrocaudal wave that mirrors this emigration pattern, initiating after neural crest specification and being down-regulated just before delamination. Functional experiments reveal that Draxin regulates the timing of cranial neural crest EMT by transiently inhibiting canonical Wnt signaling. Ectopic maintenance of Draxin in the cranial neural tube blocks full EMT; while cells delaminate, they fail to become mesenchymal and migratory. Loss of Draxin results in premature delamination but also in failure to mesenchymalize. These results suggest that a pulse of intermediate Wnt signaling triggers EMT and is necessary for its completion. Taken together, these data show that transient secreted Draxin mediates proper levels of canonical Wnt signaling required to regulate the precise timing of initiation and completion of cranial neural crest EMT

A common allele in RPGRIP1L is a modifier of retinal degeneration in ciliopathies

Despite rapid advances in the identification of genes involved in disease, the predictive power of the genotype remains limited, in part owing to poorly understood effects of second-site modifiers. Here we demonstrate that a polymorphic coding variant of RPGRIP1L (retinitis pigmentosa GTPase regulator-interacting protein-1 like), a ciliary gene mutated in Meckel-Gruber (MKS) and Joubert (JBTS) syndromes, is associated with the development of retinal degeneration in individuals with ciliopathies caused by mutations in other genes. As part of our resequencing efforts of the ciliary proteome, we identified several putative loss-of-function RPGRIP1L mutations, including one common variant, A229T. Multiple genetic lines of evidence showed this allele to be associated with photoreceptor loss in ciliopathies. Moreover, we show that RPGRIP1L interacts biochemically with RPGR, loss of which causes retinal degeneration, and that the Thr229-encoded protein significantly compromises this interaction. Our data represent an example of modification of a discrete phenotype of syndromic disease and highlight the importance of a multifaceted approach for the discovery of modifier alleles of intermediate frequency and effect.This work was supported by grants R01EY007961 from the National Eye Institute (H.K. and A.S.), R01HD04260 from the National Institute of Child Health and Development (N.K.), R01DK072301, R01DK075972 (N.K.), R01DK068306, R01DK064614, R01DK069274 (F.H.), NRSA fellowship F32 DK079541 (E.E.D.) from the National Institute of Diabetes, Digestive and Kidney disorders, Intramural program of NEI (A.S.), the Macular Vision Research Foundation (N.K.), the Foundation for Fighting Blindness (H.K., S.S.B., A.S. and N.K.), the Foundation for Fighting Blindness Canada (R.K.K.), Le Fonds de la recherche en sante du Québec (FRSQ) (R.K.K.), Research to Prevent Blindness (A.S.), Harold Falls Collegiate Professorship (A.S.), the Midwest Eye Banks and Transplantation Center (H.K.), the Searle Scholars Program (M.A.B.), the Deutsche Forschungsgemeinschaft (DFG grant BE 3910/4-1; C.B.) the UK Medical Research Council (grant number G0700073; C.A.J.), NIHR Biomedical Research Centre for Ophthalmology (S.S.B.) and EU-GENORET Grant LSHG-CT-2005-512036 (S.S.B.). F.H. is an investigator of the Howard Hughes Medical Institute (HHMI) and a Doris Duke Distinguished Clinical Scientist (DDCF)

IRR: Grounded in history: Spring 2022, issue 26

This issue in particular has a heavy focus on history. We seek not to rewrite history but to redefine it. Our emerging scholars offer critical analysis on myths, misconceptions, and misinformation. From articles on the Italian mafia, the role of agriculture in the Middle East, to the TRIPS waiver, we use history as a lesson and as a framework to guide the future of diplomacy. At the same time that we’ve engaged with global history, the International Relations Review also has sought to shift our own trajectory. The journal has historically published a print edition every year, but in the 2021 - 2022 academic year, we’ve increased both the quality and quantity of our content. With a team of more than 100 students, the International Relations Review pushes new frontiers with a podcast, blog, and journal

Tumor Endothelial Marker 8 Amplifies Canonical Wnt Signaling in Blood Vessels

Tumor Endothelial Marker 8/Anthrax Toxin Receptor 1 (TEM8/ANTXR1) expression is induced in the vascular compartment of multiple tumors and therefore, is a candidate molecule to target tumor therapies. This cell surface molecule mediates anthrax toxin internalization, however, its physiological function in blood vessels remains largely unknown. We identified the chicken chorioallantoic membrane (CAM) as a model system to study the endogenous function of TEM8 in blood vessels as we found that TEM8 expression was induced transiently between day 10 and 12 of embryonic development, when the vascular tree is undergoing final development and growth. We used the cell-binding component of anthrax toxin, Protective Antigen (PA), to engage endogenous TEM8 receptors and evaluate the effects of PA-TEM8 complexes on vascular development. PA applied at the time of highest TEM8 expression reduced vascular density and disrupted hierarchical branching as revealed by quantitative morphometric analysis of the vascular tree after 48h. PA-dependent reduced branching phenotype was partially mimicked by Wnt3a application and ameliorated by the Wnt antagonist, Dikkopf-1. These results implicate TEM8 expression in endothelial cells in regulating the canonical Wnt signaling pathway at this day of CAM development. Consistent with this model, PA increased beta catenin levels acutely in CAM blood vessels in vivo and in TEM8 transfected primary human endothelial cells in vitro. TEM8 expression in Hek293 cells, which neither express endogenous PA-binding receptors nor Wnt ligands, stabilized beta catenin levels and amplified beta catenin-dependent transcriptional activity induced by Wnt3a. This agonistic function is supported by findings in the CAM, where the increase in TEM8 expression from day 10 to day 12 and PA application correlated with Axin 2 induction, a universal reporter gene for canonical Wnt signaling. We postulate that the developmentally controlled expression of TEM8 modulates endothelial cell response to canonical Wnt signaling to regulate vessel patterning and density