Titan's latitudinal temperature distribution and seasonal cycle

Voyager IRIS brightness temperature measurements of Titan at a wavelength of 530 cm^(−1) are crudely indicative of ground or lower tropospheric temperatures and indicate 93 K for the equator and 91 K for both northern and southern high latitudes. The symmetry between north and south is unexpected for the time of Voyager encounter (Northern Titan spring). We show that this near-symmetry can arise naturally in a model where the poles are "pinned" year-round at the dew point of CH_4-N_2 lakes or, more probably, a CH_4-N_2 rich surface layer on a deep ethane-rich ocean. For a polar temperature of 91 K, the model implies that the atmosphere contains somewhat less than 8% mole fraction of CH_4

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

Specificity of bispecific T cell receptors and antibodies targeting peptide-HLA

Tumor-associated peptide–human leukocyte antigen complexes (pHLAs) represent the largest pool of cell surface–expressed cancer-specific epitopes, making them attractive targets for cancer therapies. Soluble bispecific molecules that incorporate an anti-CD3 effector function are being developed to redirect T cells against these targets using 2 different approaches. The first achieves pHLA recognition via affinity-enhanced versions of natural TCRs (e.g., immune-mobilizing monoclonal T cell receptors against cancer [ImmTAC] molecules), whereas the second harnesses an antibody-based format (TCR-mimic antibodies). For both classes of reagent, target specificity is vital, considering the vast universe of potential pHLA molecules that can be presented on healthy cells. Here, we made use of structural, biochemical, and computational approaches to investigate the molecular rules underpinning the reactivity patterns of pHLA-targeting bispecifics. We demonstrate that affinity-enhanced TCRs engage pHLA using a comparatively broad and balanced energetic footprint, with interactions distributed over several HLA and peptide side chains. As ImmTAC molecules, these TCRs also retained a greater degree of pHLA selectivity, with less off-target activity in cellular assays. Conversely, TCR-mimic antibodies tended to exhibit binding modes focused more toward hot spots on the HLA surface and exhibited a greater degree of crossreactivity. Our findings extend our understanding of the basic principles that underpin pHLA selectivity and exemplify a number of molecular approaches that can be used to probe the specificity of pHLA-targeting molecules, aiding the development of future reagents

US SOLAS Science Report

The article of record may be found at https://doi.org/10.1575/1912/27821The Surface Ocean – Lower Atmosphere Study (SOLAS) (http://www.solas-int.org/) is an international research initiative focused on understanding the key biogeochemical-physical interactions and feedbacks between the ocean and atmosphere that are critical elements of climate and global biogeochemical cycles. Following the release of the SOLAS Decadal Science Plan (2015-2025) (Brévière et al., 2016), the Ocean-Atmosphere Interaction Committee (OAIC) was formed as a subcommittee of the Ocean Carbon and Biogeochemistry (OCB) Scientific Steering Committee to coordinate US SOLAS efforts and activities, facilitate interactions among atmospheric and ocean scientists, and strengthen US contributions to international SOLAS. In October 2019, with support from OCB, the OAIC convened an open community workshop, Ocean-Atmosphere Interactions: Scoping directions for new research with the goal of fostering new collaborations and identifying knowledge gaps and high-priority science questions to formulate a US SOLAS Science Plan. Based on presentations and discussions at the workshop, the OAIC and workshop participants have developed this US SOLAS Science Plan. The first part of the workshop and this Science Plan were purposefully designed around the five themes of the SOLAS Decadal Science Plan (2015-2025) (Brévière et al., 2016) to provide a common set of research priorities and ensure a more cohesive US contribution to international SOLAS.This report was developed with federal support of NSF (OCE-1558412) and NASA (NNX17AB17G).This report was developed with federal support of NSF (OCE-1558412) and NASA (NNX17AB17G)

US SOLAS Science Report

The Surface Ocean – Lower Atmosphere Study (SOLAS) (http://www.solas-int.org/) is an international research initiative focused on understanding the key biogeochemical-physical interactions and feedbacks between the ocean and atmosphere that are critical elements of climate and global biogeochemical cycles. Following the release of the SOLAS Decadal Science Plan (2015-2025) (Brévière et al., 2016), the Ocean-Atmosphere Interaction Committee (OAIC) was formed as a subcommittee of the Ocean Carbon and Biogeochemistry (OCB) Scientific Steering Committee to coordinate US SOLAS efforts and activities, facilitate interactions among atmospheric and ocean scientists, and strengthen US contributions to international SOLAS. In October 2019, with support from OCB, the OAIC convened an open community workshop, Ocean-Atmosphere Interactions: Scoping directions for new research with the goal of fostering new collaborations and identifying knowledge gaps and high-priority science questions to formulate a US SOLAS Science Plan. Based on presentations and discussions at the workshop, the OAIC and workshop participants have developed this US SOLAS Science Plan. The first part of the workshop and this Science Plan were purposefully designed around the five themes of the SOLAS Decadal Science Plan (2015-2025) (Brévière et al., 2016) to provide a common set of research priorities and ensure a more cohesive US contribution to international SOLAS.This report was developed with federal support of NSF (OCE-1558412) and NASA (NNX17AB17G)

Genome-Wide Search for Gene-Gene Interactions in Colorectal Cancer

Genome-wide association studies (GWAS) have successfully identified a number of single-nucleotide polymorphisms (SNPs) associated with colorectal cancer (CRC) risk. However, these susceptibility loci known today explain only a small fraction of the genetic risk. Gene-gene interaction (GxG) is considered to be one source of the missing heritability. To address this, we performed a genome-wide search for pair-wise GxG associated with CRC risk using 8,380 cases and 10,558 controls in the discovery phase and 2,527 cases and 2,658 controls in the replication phase. We developed a simple, but powerful method for testing interaction, which we term the Average Risk Due to Interaction (ARDI). With this method, we conducted a genome-wide search to identify SNPs showing evidence for GxG with previously identified CRC susceptibility loci from 14 independent regions. We also conducted a genome-wide search for GxG using the marginal association screening and examining interaction among SNPs that pass the screening threshold (p<$10^{−4}$). For the known locus rs10795668 (10p14), we found an interacting SNP rs367615 (5q21) with replication p = 0.01 and combined p = 4.19×$10^{−8}$. Among the top marginal SNPs after LD pruning (n = 163), we identified an interaction between rs1571218 (20p12.3) and rs10879357 (12q21.1) (nominal combined p = 2.51×$10^{−6}$; Bonferroni adjusted p = 0.03). Our study represents the first comprehensive search for GxG in CRC, and our results may provide new insight into the genetic etiology of CRC

Trapping \u3ci\u3ePhyllophaga \u3c/i\u3espp. (Coleoptera: Scarabaeidae: Melolonthinae) in the United States and Canada using sex attractants.

The sex pheromone of the scarab beetle, Phyllophaga anxia, is a blend of the methyl esters of two amino acids, L-valine and L-isoleucine. A field trapping study was conducted, deploying different blends of the two compounds at 59 locations in the United States and Canada. More than 57,000 males of 61 Phyllophaga species (Coleoptera: Scarabaeidae: Melolonthinae) were captured and identified. Three major findings included: (1) widespread use of the two compounds [of the 147 Phyllophaga (sensu stricto) species found in the United States and Canada, males of nearly 40% were captured]; (2) in most species intraspecific male response to the pheromone blends was stable between years and over geography; and (3) an unusual pheromone polymorphism was described from P. anxia. Populations at some locations were captured with L-valine methyl ester alone, whereas populations at other locations were captured with L-isoleucine methyl ester alone. At additional locations, the L-valine methyl ester-responding populations and the L-isoleucine methyl ester-responding populations were both present, producing a bimodal capture curve. In southeastern Massachusetts and in Rhode Island, in the United States, P. anxia males were captured with blends of L-valine methyl ester and L-isoleucine methyl ester

Diet and Energy-Sensing Inputs Affect TorC1-Mediated Axon Misrouting but Not TorC2-Directed Synapse Growth in a Drosophila Model of Tuberous Sclerosis

The Target of Rapamycin (TOR) growth regulatory system is influenced by a number of different inputs, including growth factor signaling, nutrient availability, and cellular energy levels. While the effects of TOR on cell and organismal growth have been well characterized, this pathway also has profound effects on neural development and behavior. Hyperactivation of the TOR pathway by mutations in the upstream TOR inhibitors TSC1 (tuberous sclerosis complex 1) or TSC2 promotes benign tumors and neurological and behavioral deficits, a syndrome known as tuberous sclerosis (TS). In Drosophila, neuron-specific overexpression of Rheb, the direct downstream target inhibited by Tsc1/Tsc2, produced significant synapse overgrowth, axon misrouting, and phototaxis deficits. To understand how misregulation of Tor signaling affects neural and behavioral development, we examined the influence of growth factor, nutrient, and energy sensing inputs on these neurodevelopmental phenotypes. Neural expression of Pi3K, a principal mediator of growth factor inputs to Tor, caused synapse overgrowth similar to Rheb, but did not disrupt axon guidance or phototaxis. Dietary restriction rescued Rheb-mediated behavioral and axon guidance deficits, as did overexpression of AMPK, a component of the cellular energy sensing pathway, but neither was able to rescue synapse overgrowth. While axon guidance and behavioral phenotypes were affected by altering the function of a Tor complex 1 (TorC1) component, Raptor, or a TORC1 downstream element (S6k), synapse overgrowth was only suppressed by reducing the function of Tor complex 2 (TorC2) components (Rictor, Sin1). These findings demonstrate that different inputs to Tor signaling have distinct activities in nervous system development, and that Tor provides an important connection between nutrient-energy sensing systems and patterning of the nervous system

MAVS-Mediated Apoptosis and Its Inhibition by Viral Proteins

BACKGROUND: Host responses to viral infection include both immune activation and programmed cell death. The mitochondrial antiviral signaling adaptor, MAVS (IPS-1, VISA or Cardif) is critical for host defenses to viral infection by inducing type-1 interferons (IFN-I), however its role in virus-induced apoptotic responses has not been elucidated. PRINCIPAL FINDINGS: We show that MAVS causes apoptosis independent of its function in initiating IFN-I production. MAVS-induced cell death requires mitochondrial localization, is caspase dependent, and displays hallmarks of apoptosis. Furthermore, MAVS(-/-) fibroblasts are resistant to Sendai virus-induced apoptosis. A functional screen identifies the hepatitis C virus NS3/4A and the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) nonstructural protein (NSP15) as inhibitors of MAVS-induced apoptosis, possibly as a method of immune evasion. SIGNIFICANCE: This study describes a novel role for MAVS in controlling viral infections through the induction of apoptosis, and identifies viral proteins which inhibit this host response