An Excess of Jupiter Analogs in Super-Earth Systems

We use radial velocity observations to search for long-period gas giant companions in systems hosting inner super-Earth (1-4 R_Earth, 1-10 M_Earth) planets to constrain formation and migration scenarios for this population. We consistently re-fit published RV datasets for 65 stars and find 9 systems with statistically significant trends indicating the presence of an outer companion. We combine these RV data with AO images to constrain the masses and semi-major axes of these companions. We quantify our sensitivity to the presence of long-period companions by fitting the sample with a power law distribution and find an occurrence rate of 39+/-7% for companions 0.5-20 M_Jup and 1-20 AU. Half of our systems were discovered by the transit method and half were discovered by the RV method. While differences in RV baselines and number of data points between the two samples lead to different sensitivities to distant companions, we find that occurrence rates of gas giant companions in each sample are consistent at the 0.5$\sigma$ level. We compare the frequency of Jupiter analogs in these systems to the equivalent rate from field star surveys and find that Jupiter analogs are more common around stars hosting super-Earths. We conclude that the presence of outer gas giants does not suppress the formation of inner super-Earths, and that these two populations of planets instead appear to be correlated. We also find that the stellar metallicities of systems with gas giant companions are higher than those without companions, in agreement with the well-established metallicity correlation from RV surveys of field stars.Comment: published in A

Qualitative assessment of a Context of Consumption Framework to inform regulation of cigarette pack design in the U.S.

INTRODUCTION Researchers and regulators need to know how changes to cigarette packages can influence population health. We sought to advance research on the role of cigarette packaging by assessing a theory-informed framework from the fields of design and consumer research. The selected Context of Consumption Framework posits cognitive, affective, and behavioral responses to visual design. To assess the Framework’s potential for guiding research on the visual design of cigarette packaging in the U.S., this study seeks to understand to what extent the Context of Consumption Framework converges with how adult smokers think and talk about cigarette pack designs. METHODS Data for this qualitative study came from six telephone-based focus groups conducted in March 2017. Two groups consisted of lesbian, gay, and bisexual participants; two groups of participants with less than four years college education; one group of LGB and straight identity; and one group the general population. All groups were selected for regional, gender, and racial/ethnic diversity. Participants (n=33) represented all nine U.S. Census divisions. We conducted a deductive qualitative analysis. RESULTS Cigarette package designs captured the participants’ attention, suggested the characteristics of the product, and reflected (or could be leveraged to convey) multiple dimensions of consumer identity. Particular to the affective responses to design, our participants shared that cigarette packaging conveyed how the pack could be used to particular ends, created an emotional response to the designs, complied with normative expectations of a cigarette, elicited interest when designs change, and prompted fascination when unique design characteristics are used. CONCLUSIONS Use of the Context of Consumption Framework for cigarette product packaging design can inform regulatory research on tobacco product packaging. Researchers and regulators should consider multiple cognitive, affective, and behavioral responses to cigarette pack design

An Efficient, Green Chemical Synthesis of the Malaria\ud Drug, Piperaquine

To provide a robust, efficient synthesis of the malaria drug piperaquine for potential use in resource-poor settings. We used in-process analytical technologies (IPAT; HPLC) and a program of experiments to develop a synthesis of piperaquine that avoids the presence of a toxic impurity in the API and is optimized for overall yield and operational simplicity. A green-chemical synthesis of piperaquine is described that proceeds in 92 – 93 % overall yield. The chemistry is robust and provides very pure piperaquine tetraphosphate salt (> 99.5 %). The overall process utilizes modest amounts (about 8 kg/kg) of 2-propanol and ethyl acetate as the only organic materials not incorporated into the API; roughly 60 % of this waste can be recycled into the production process. This process also completely avoids the formation of a toxic impurity commonly seen in piperaquine that is otherwise difficult to remove. An efficient synthesis of piperaquine is described that may be useful for application in resource-poor settings as a means of expanding access to and reducing the cost of ACTs

GAD1 Upregulation Programs Aggressive Features of Cancer Cell Metabolism in the Brain Metastatic Microenvironment

The impact of altered amino acid metabolism on cancer progression is not fully understood. We hypothesized that a metabolic transcriptome shift during metastatic evolution is crucial for brain metastasis. Here, we report a powerful impact in this setting caused by epigenetic upregulation of glutamate decarboxylase 1 (GAD1), a regulator of the GABA neurotransmitter metabolic pathway. In cell-based culture and brain metastasis models, we found that downregulation of the DNA methyltransferase DNMT1 induced by the brain microenvironment-derived clusterin resulted in decreased GAD1 promoter methylation and subsequent upregulation of GAD1 expression in brain metastatic tumor cells. In a system to dynamically visualize cellular metabolic responses mediated by GAD1, we monitored the cytosolic NADH:NAD+ equilibrium in tumor cells. Reducing GAD1 in metastatic cells by primary glia cell coculture abolished the capacity of metastatic cells to utilize extracellular glutamine, leading to cytosolic accumulation of NADH and increased oxidative status. Similarly, genetic or pharmacologic disruption of the GABA metabolic pathway decreased the incidence of brain metastasis in vivo Taken together, our results show how epigenetic changes in GAD1 expression alter local glutamate metabolism in the brain metastatic microenvironment, contributing to a metabolic adaption that facilitates metastasis outgrowth in that setting

Sprouty2 in the Dorsal Hippocampus Regulates Neurogenesis and Stress Responsiveness in Rats

Both the development and relief of stress-related psychiatric conditions such as major depression (MD) and post-traumatic stress disorder (PTSD) have been linked to neuroplastic changes in the brain. One such change involves the birth of new neurons (neurogenesis), which occurs throughout adulthood within discrete areas of the mammalian brain, including the dorsal hippocampus (HIP). Stress can trigger MD and PTSD in humans, and there is considerable evidence that it can decrease HIP neurogenesis in laboratory animals. In contrast, antidepressant treatments increase HIP neurogenesis, and their efficacy is eliminated by ablation of this process. These findings have led to the working hypothesis that HIP neurogenesis serves as a biomarker of neuroplasticity and stress resistance. Here we report that local alterations in the expression of Sprouty2 (SPRY2), an intracellular inhibitor of growth factor function, produces profound effects on both HIP neurogenesis and behaviors that reflect sensitivity to stressors. Viral vector-mediated disruption of endogenous Sprouty2 function (via a dominant negative construct) within the dorsal HIP of adult rats stimulates neurogenesis and produces signs of stress resilience including enhanced extinction of conditioned fear. Conversely, viral vector-mediated elevation of SPRY2 expression intensifies the behavioral consequences of stress. Studies of these manipulations in HIP primary cultures indicate that SPRY2 negatively regulates fibroblast growth factor-2 (FGF2), which has been previously shown to produce antidepressant- and anxiolytic-like effects via actions in the HIP. Our findings strengthen the relationship between HIP plasticity and stress responsiveness, and identify a specific intracellular pathway that could be targeted to study and treat stress-related disorders

Identification of CCR8: A Human Monocyte and Thymus Receptor for the CC Chemokine I-309

The human CC chemokine I-309 is a potent monocyte chemoattractant and inhibits apoptosis in thymic cell lines. Here, we identify a specific human I-309 receptor, and name it CCR8 according to an accepted nomenclature system. The receptor has seven predicted transmembrane domains, is expressed constitutively in monocytes and thymus, and is encoded by a previously reported gene of previously unknown function named, alternatively, CY6, TER1, and CKR-L1. After transfection with the CY6 open reading frame, a mouse pre–B cell line exhibited calcium flux and chemotaxis in response to I-309 (EC50 = 2 nM for each), whereas 20 other chemokines were inactive. Signaling was sensitive to pertussis toxin, suggesting coupling to a Gi-type G protein. These properties parallel those of endogenous I-309 receptors expressed in an HL-60 clone 15 cell line model. The apparent monogamous relationship between I-309 and CCR8 is unusual among known CC chemokines and known CC chemokine receptors. CCR8 may regulate monocyte chemotaxis and thymic cell line apoptosis

An Excess of Jupiter Analogs in Super-Earth Systems

We use radial velocity (RV) observations to search for long-period gas giant companions in systems hosting inner super-Earth (1–4 R⊕, 1–10 M⊕) planets to constrain formation and migration scenarios for this population. We consistently refit published RV data sets for 65 stars and find nine systems with statistically significant trends indicating the presence of an outer companion. We combine these RV data with AO images to constrain the masses and semi-major axes of these companions. We quantify our sensitivity to the presence of long-period companions by fitting the sample with a power-law distribution and find an occurrence rate of 39% ± 7% for companions 0.5–20 M_(Jup) and 1–20 au. Half of our systems were discovered by the transit method, and half were discovered by the RV method. While differences in the RV baselines and number of data points between the two samples lead to different sensitivities to distant companions, we find that occurrence rates of gas giant companions in each sample are consistent at the 0.5σ level. We compare the frequency of Jupiter analogs in these systems to the equivalent rate from field star surveys and find that Jupiter analogs are more common around stars hosting super-Earths. We conclude that the presence of outer gas giants does not suppress the formation of inner super-Earths, and that these two populations of planets instead appear to be correlated. We also find that the stellar metallicities of systems with gas giant companions are higher than those without companions, in agreement with the well-established metallicity correlation from RV surveys of field stars

Cluster M Mycobacteriophages Bongo, PegLeg, and Rey with Unusually Large Repertoires of tRNA Isotopes

Genomic analysis of a large set of phages infecting the common hostMycobacterium smegmatis mc2155 shows that they span considerable genetic diversity. There are more than 20 distinct types that lack nucleotide similarity with each other, and there is considerable diversity within most of the groups. Three newly isolated temperate mycobacteriophages, Bongo, PegLeg, and Rey, constitute a new group (cluster M), with the closely related phages Bongo and PegLeg forming subcluster M1 and the more distantly related Rey forming subcluster M2. The cluster M mycobacteriophages have siphoviral morphologies with unusually long tails, are homoimmune, and have larger than average genomes (80.2 to 83.7 kbp). They exhibit a variety of features not previously described in other mycobacteriophages, including noncanonical genome architectures and several unusual sets of conserved repeated sequences suggesting novel regulatory systems for both transcription and translation. In addition to containing transfer-messenger RNA and RtcB-like RNA ligase genes, their genomes encode 21 to 24 tRNA genes encompassing complete or nearly complete sets of isotypes. We predict that these tRNAs are used in late lytic growth, likely compensating for the degradation or inadequacy of host tRNAs. They may represent a complete set of tRNAs necessary for late lytic growth, especially when taken together with the apparent lack of codons in the same late genes that correspond to tRNAs that the genomes of the phages do not obviously encode

Response to comment on 'Amphibian fungal panzootic causes catastrophic and ongoing loss of biodiversity'

Lambert et al. question our retrospective and holistic epidemiological assessment of the role of chytridiomycosis in amphibian declines. Their alternative assessment is narrow and provides an incomplete evaluation of evidence. Adopting this approach limits understanding of infectious disease impacts and hampers conservation efforts. We reaffirm that our study provides unambiguous evidence that chytridiomycosis has affected at least 501 amphibian species