Different methods of fear reduction are supported by distinct cortical substrates

Understanding how learned fear can be reduced is at the heart of treatments for anxiety disorders. Tremendous progress has been made in this regard through extinction training in which the aversive outcome is omitted. However, current progress almost entirely rests on this single paradigm, resulting in a very specialized knowledgebase at the behavioural and neural level of analysis. Here, we used a dual-paradigm approach to show that different methods that lead to reduction in learned fear in rats are dissociated in the cortex. We report that the infralimbic cortex has a very specific role in fear reduction that depends on the omission of aversive events but not on overexpectation. The orbitofrontal cortex, a structure generally overlooked in fear, is critical for downregulating fear when novel predictions about upcoming aversive events are generated, such as when fear is inflated or overexpected, but less so when an expected aversive event is omitted

Unmapped RNA Virus Diversity in Termites and Their Symbionts

Despite their ecological importance, nothing is known about the diversity and abundance of RNA viruses in termites (Termitoidae). We used a metatranscriptomics approach to determine the RNA virome structure of 50 diverse species of termite that differ in both phylogenetic position and colony composition. From these samples, we identified 67 novel RNA viruses, characterized their genomes, quantified their abundance and inferred their evolutionary history. These viruses were found within or similar to those from the Togaviridae, Iflaviridae, Polycipiviridae, Flaviviridae, Leviviridae, Narnaviridae, Mitoviridae, Lispivirdae, Phasmaviridae, Picobirnaviridae and Partitiviridae. However, all viruses identified were novel and divergent, exhibiting only 20% to 45% amino acid identity to previously identified viruses. Our analysis suggested that 17 of the viruses identified were termite-infecting, with the remainder likely associated with the termite microbiome or diet. Unclassified sobemo-like and bunya-like viruses dominated termite viromes, while most of the phylogenetic diversity was provided by the picobirna- and mitovirus-like viruses. Of note was the identification of a novel flavi-like virus most closely related to those found in marine vertebrates and invertebrates. Notably, the sampling procedure had the strongest association with virome composition, with greater RNA virome diversity in libraries prepared from whole termite bodies than those that only sampled heads

SARS-CoV-2 Infects Human Pluripotent Stem Cell-Derived Cardiomyocytes, Impairing Electrical and Mechanical Function

COVID-19 patients often develop severe cardiovascular complications, but it remains unclear if these are caused directly by viral infection or are secondary to a systemic response. Here, we examine the cardiac tropism of SARS-CoV-2 in human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and smooth muscle cells (hPSC-SMCs). We find that that SARS-CoV-2 selectively infects hPSC-CMs through the viral receptor ACE2, whereas in hPSC-SMCs there is minimal viral entry or replication. After entry into cardiomyocytes, SARS-CoV-2 is assembled in lysosome-like vesicles and egresses via bulk exocytosis. The viral transcripts become a large fraction of cellular mRNA while host gene expression shifts from oxidative to glycolytic metabolism and upregulates chromatin modification and RNA splicing pathways. Most importantly, viral infection of hPSC-CMs progressively impairs both their electrophysiological and contractile function, and causes widespread cell death. These data support the hypothesis that COVID-19-related cardiac symptoms can result from a direct cardiotoxic effect of SARS-CoV-2

Blue Carbon Science, Management and Policy Across a Tropical Urban Landscape

The ability of vegetated coastal ecosystems to sequester high rates of “blue” carbon over millennial time scales has attracted the interest of national and international policy makers as a tool for climate change mitigation. Whereas focus on blue carbon conservation has been mostly on threatened rural seascapes, there is scope to consider blue carbon dynamics along highly fragmented and developed urban coastlines. The tropical city state of Singapore is used as a case study of urban blue carbon knowledge generation, how blue carbon changes over time with urban development, and how such knowledge can be integrated into urban planning alongside municipal and national climate change obligations. A systematic review of blue carbon studies in Singapore was used to support a qualitative review of Singapore’s blue carbon ecosystems, carbon budget, changes through time and urban planning and policy. Habitat loss across all blue carbon ecosystems is coarsely estimated to have resulted in the release of ∼12.6 million tonnes of carbon dioxide since the beginning of the 20th century. However, Singapore’s remaining blue carbon ecosystems still store an estimated 568,971 – 577,227 tonnes of carbon (equivalent to 2.1 million tonnes of carbon dioxide) nationally, with a small proportion of initial loss offset by habitat restoration. Carbon is now a key topic on the urban development and planning agenda, as well as nationally through Singapore’s contributions to the Paris Agreement. The experiences of Singapore show that coastal ecosystems and their blue carbon stocks can be successfully managed along an urban coastline, and can help inform blue carbon science and management along other rapidly urbanizing coastlines throughout the tropics

Campath, calcineurin inhibitor reduction and chronic allograft nephropathy (3C) study: background, rationale, and study protocol.

BACKGROUND: Kidney transplantation is the best treatment for patients with end-stage renal failure, but uncertainty remains about the best immunosuppression strategy. Long-term graft survival has not improved substantially, and one possible explanation is calcineurin inhibitor (CNI) nephrotoxicity. CNI exposure could be minimized by using more potent induction therapy or alternative maintenance therapy to remove CNIs completely. However, the safety and efficacy of such strategies are unknown. METHODS/DESIGN: The Campath, Calcineurin inhibitor reduction and Chronic allograft nephropathy (3C) Study is a multicentre, open-label, randomized controlled trial with 852 participants which is addressing two important questions in kidney transplantation. The first question is whether a Campath (alemtuzumab)-based induction therapy strategy is superior to basiliximab-based therapy, and the second is whether, from 6 months after transplantation, a sirolimus-based maintenance therapy strategy is superior to tacrolimus-based therapy. Recruitment is complete, and follow-up will continue for around 5 years post-transplant. The primary endpoint for the induction therapy comparison is biopsy-proven acute rejection by 6 months, and the primary endpoint for the maintenance therapy comparison is change in estimated glomerular filtration rate from baseline to 2 years after transplantation. The study is sponsored by the University of Oxford and endorsed by the British Transplantation Society, and 18 centers for adult kidney transplant are participating. DISCUSSION: Late graft failure is a major issue for kidney-transplant recipients. If our hypothesis that minimizing CNI exposure with Campath-based induction therapy and/or an elective conversion to sirolimus-based maintenance therapy can improve long-term graft function and survival is correct, then patients should experience better graft function for longer. A positive outcome could change clinical practice in kidney transplantation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01120028 and ISRCTN88894088.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Quantum Gas Mixtures and Dual-Species Atom Interferometry in Space

The capability to reach ultracold atomic temperatures in compact instruments has recently been extended into space. Ultracold temperatures amplify quantum effects, while free-fall allows further cooling and longer interactions time with gravity - the final force without a quantum description. On Earth, these devices have produced macroscopic quantum phenomena such as Bose-Einstein condensation (BECs), superfluidity, and strongly interacting quantum gases. Quantum sensors interfering the superposition of two ultracold atomic isotopes have tested the Universality of Free Fall (UFF), a core tenet of Einstein's classical gravitational theory, at the $10^{-12}$ level. In space, cooling the elements needed to explore the rich physics of strong interactions and preparing the multiple species required for quantum tests of the UFF has remained elusive. Here, utilizing upgraded capabilities of the multi-user Cold Atom Lab (CAL) instrument within the International Space Station (ISS), we report the first simultaneous production of a dual species Bose-Einstein condensate in space (formed from $^{87}$Rb and $^{41}$K), observation of interspecies interactions, as well as the production of $^{39}$K ultracold gases. We have further achieved the first space-borne demonstration of simultaneous atom interferometry with two atomic species ($^{87}$Rb and $^{41}$K). These results are an important step towards quantum tests of UFF in space, and will allow scientists to investigate aspects of few-body physics, quantum chemistry, and fundamental physics in novel regimes without the perturbing asymmetry of gravity