Statistical Analysis of Molecular Signal Recording

A molecular device that records time-varying signals would enable new approaches in neuroscience. We have recently proposed such a device, termed a “molecular ticker tape”, in which an engineered DNA polymerase (DNAP) writes time-varying signals into DNA in the form of nucleotide misincorporation patterns. Here, we define a theoretical framework quantifying the expected capabilities of molecular ticker tapes as a function of experimental parameters. We present a decoding algorithm for estimating time-dependent input signals, and DNAP kinetic parameters, directly from misincorporation rates as determined by sequencing. We explore the requirements for accurate signal decoding, particularly the constraints on (1) the polymerase biochemical parameters, and (2) the amplitude, temporal resolution, and duration of the time-varying input signals. Our results suggest that molecular recording devices with kinetic properties similar to natural polymerases could be used to perform experiments in which neural activity is compared across several experimental conditions, and that devices engineered by combining favorable biochemical properties from multiple known polymerases could potentially measure faster phenomena such as slow synchronization of neuronal oscillations. Sophisticated engineering of DNAPs is likely required to achieve molecular recording of neuronal activity with single-spike temporal resolution over experimentally relevant timescales.United States. Defense Advanced Research Projects Agency. Living Foundries ProgramGoogle (Firm)New York Stem Cell Foundation. Robertson Neuroscience Investigator AwardNational Institutes of Health (U.S.) (EUREKA Award 1R01NS075421)National Institutes of Health (U.S.) (Transformative R01 1R01GM104948)National Institutes of Health (U.S.) (Single Cell Grant 1 R01 EY023173)National Institutes of Health (U.S.) (Grant 1R01DA029639)National Institutes of Health (U.S.) (Grant 1R01NS067199)National Science Foundation (U.S.) (CAREER Award CBET 1053233)National Science Foundation (U.S.) (Grant EFRI0835878)National Science Foundation (U.S.) (Grant DMS1042134)Paul G. Allen Family Foundation (Distinguished Investigator in Neuroscience Award

Deviant Peer Affiliation and Antisocial Behavior: Interaction with Monoamine Oxidase A (MAOA) Genotype

Although genetic and environmental factors are separately implicated in the development of antisocial behavior (ASB), interactive models have emerged relatively recently, particularly those incorporating molecular genetic data. Using a large sample of male Caucasian adolescents and young adults from the National Longitudinal Study of Adolescent Health (Add Health), the association of deviant peer affiliation, the 30-base pair variable number tandem repeat polymorphism in promoter region of the monoamine oxidase-A (MAOA) gene, and their interaction, with antisocial behavior (ASB) was investigated. Weighted analyses accounting for over-sampling and clustering within schools as well as controlling for age and wave suggested that deviant peer affiliation and MAOA genotype were each significantly associated with levels of overt ASB across a 6-year period. Only deviant peer affiliation was significantly related to covert ASB, however. Additionally, there was evidence suggestive of a gene-environment interaction (G × E) where the influence of deviant peer affiliation on overt ASB was significantly stronger among individuals with the high-activity MAOA genotype than the low-activity genotype. MAOA was not significantly associated with deviant peer affiliation, thus strengthening the inference of G × E rather than gene-environment correlation (rGE). Different forms of gene-environment interplay and implications for future research on ASB are discussed

Who Laughs at a Rape Joke? Illiberal Responsiveness in Rodrigo Duterte\u27s Philippines

When a presidential contender makes a joke about lusting over a dead Australian missionary, calls the Pope the son of a whore, and confesses to killing criminals during his tenure as city mayor, one could expect that this candidate would not go very far. But not in the year 2016. Dubbed as ‘the year of voting dangerously,’ the Philippines rode the tide of global discontent and gave landslide victory to the controversial Rodrigo Duterte. This chapter examines the discursive underpinnings of Duterte’s rise to power by focusing on the process in which his supporters made ethical calculations from listening to his official speeches, live performance on television debates, and broader discussions in news and social media during the campaign period. We argue that Duterte’s ‘crass politics’ is a push back to the dominant moral politics perpetuated by institutions associated to the Philippines\u27 liberal democratic elite. While we condemn the Duterte regime’s disregard for human rights and due process, especially in the context of his bloody war on drugs, we also advocate a closer look at the ethics of Duterte’s responsiveness to deep-seated injuries endured by his constituencies both among marginalised and middle-class communities. Through a careful yet critical unpacking of his ‘crass politics of responsiveness’ from ethnographic research with Duterte supporters and media analysis of Duterte’s public performances, we hope to put forward a precise understanding of the emerging moral politics that underpins this unorthodox regime

Quantifying the Spatial Ecology of Wide-Ranging Marine Species in the Gulf of California: Implications for Marine Conservation Planning

There is growing interest in systematic establishment of marine protected area (MPA) networks and representative conservation sites. This movement toward networks of no-take zones requires that reserves are deliberately and adequately spaced for connectivity. Here, we test the network functionality of an ecoregional assessment configuration of marine conservation areas by evaluating the habitat protection and connectivity offered to wide-ranging fauna in the Gulf of California (GOC, Mexico). We first use expert opinion to identify representative species of wide-ranging fauna of the GOC. These include leopard grouper, hammerhead sharks, California brown pelicans and green sea turtles. Analyzing habitat models with both structural and functional connectivity indexes, our results indicate that the configuration includes large proportions of biologically important habitat for the four species considered (25–40%), particularly, the best quality habitats (46–57%). Our results also show that connectivity levels offered by the conservation area design for these four species may be similar to connectivity levels offered by the entire Gulf of California, thus indicating that connectivity offered by the areas may resemble natural connectivity. The selected focal species comprise different life histories among marine or marine-related vertebrates and are associated with those habitats holding the most biodiversity values (i.e. coastal habitats); our results thus suggest that the proposed configuration may function as a network for connectivity and may adequately represent the marine megafauna in the GOC, including the potential connectivity among habitat patches. This work highlights the range of approaches that can be used to quantify habitat protection and connectivity for wide-ranging marine species in marine reserve networks

Use of the Pediatric Symptom Checklist for the detection of psychosocial problems in preventive child healthcare

BACKGROUND: Early detection and treatment of psychosocial problems by preventive child healthcare may lead to considerable health benefits, and a short questionnaire could support this aim. The aim of this study was to assess whether the Dutch version of the US Pediatric Symptom checklist (PSC) is valid and suitable for the early detection of psychosocial problems among children. METHODS: We included 687 children (response 84.3%) aged 7–12 undergoing routine health assessments in nine Preventive Child Health Services across the Netherlands. Child health professionals interviewed and examined children and parents. Before the interview, parents completed an authorised Dutch translation of the PSC and the Child Behavior Checklist (CBCL). The CBCL and data on the child's current treatment status were used as criteria for the validity of the PSC. RESULTS: The consistency of the Dutch PSC was good (Cronbach alpha 0.89). The area under the ROC curve using the CBCL as a criterion was 0.94 (95% confidence interval 0.92 to 0.96). At the US cut-off (28 and above), the prevalence rate of an increased score and sensitivity were lower than in the USA. At a lower cut-off (22 and above), sensitivity and specificity were similar to that of the US version (71.7% and 93.0% respectively). Information on the PSC also helped in the identification of children with elevated CBCL Total Problems Scores, above solely clinical judgment. CONCLUSION: The PSC is also useful for the early detection of psychosocial problems in preventive child healthcare outside the USA, especially with an adjusted cut-off

High Connectivity in the Deepwater Snapper Pristipomoides filamentosus (Lutjanidae) across the Indo-Pacific with Isolation of the Hawaiian Archipelago

In the tropical Indo-Pacific, most phylogeographic studies have focused on the shallow-water taxa that inhabit reefs to approximately 30 m depth. Little is known about the large predatory fishes, primarily snappers (subfamily Etelinae) and groupers (subfamily Epinephelinae) that occur at 100–400 m. These long-lived, slow-growing species support fisheries across the Indo-Pacific, yet no comprehensive genetic surveys within this group have been conducted. Here we contribute the first range-wide survey of a deepwater Indo-Pacific snapper, Pristipomoides filamentosus, with special focus on Hawai'i. We applied mtDNA cytochrome b and 11 microsatellite loci to 26 samples (N = 1,222) collected across 17,000 km from Hawai'i to the western Indian Ocean. Results indicate that P. filamentosus is a highly dispersive species with low but significant population structure (mtDNA ΦST = 0.029, microsatellite FST = 0.029) due entirely to the isolation of Hawai'i. No population structure was detected across 14,000 km of the Indo-Pacific from Tonga in the Central Pacific to the Seychelles in the western Indian Ocean, a pattern rarely observed in reef species. Despite a long pelagic phase (60–180 days), interisland dispersal as adults, and extensive gene flow across the Indo-Pacific, P. filamentosus is unable to maintain population connectivity with Hawai'i. Coalescent analyses indicate that P. filamentosus may have colonized Hawai'i 26 K–52 K y ago against prevailing currents, with dispersal away from Hawai'i dominating migration estimates. P. filamentosus harbors low genetic diversity in Hawai'i, a common pattern in marine fishes, and our data indicate a single archipelago-wide stock. However, like the Hawaiian Grouper, Hyporthodus quernus, this snapper had several significant pairwise comparisons (FST) clustered around the middle of the archipelago (St. Rogatien, Brooks Banks, Gardner) indicating that this region may be isolated or (more likely) receives input from Johnston Atoll to the south

Evaluation of an early detection tool for social-emotional and behavioral problems in toddlers: The Brief Infant Toddler Social and Emotional Assessment - A cluster randomized trial

<p>Abstract</p> <p>Background</p> <p>The prevalence of social-emotional and behavioral problems is estimated to be 8 to 9% among preschool children. Effective early detection tools are needed to promote the provision of adequate care at an early stage. The Brief Infant-Toddler Social and Emotional Assessment (BITSEA) was developed for this purpose. This study evaluates the effectiveness of the BITSEA to enhance social-emotional and behavioral health of preschool children.</p> <p>Methods and Design</p> <p>A cluster randomized controlled trial is set up in youth health care centers in the larger Rotterdam area in the Netherlands, to evaluate the BITSEA. The 31 youth health care centers are randomly allocated to either the control group or the intervention group. The intervention group uses the scores on the BITSEA and cut-off points to evaluate a child's social-emotional and behavioral health and to decide whether or not the child should be referred. The control group provides care as usual, which involves administering a questionnaire that structures the conversation between child health professionals and parents. At a one year follow-up measurement the social-emotional and behavioral health of all children included in the study population will be evaluated.</p> <p>Discussion</p> <p>It is hypothesized that better results will be found, in terms of social-emotional and behavioral health in the intervention group, compared to the control group, due to more adequate early detection, referral and more appropriate and timely care.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2035">NTR2035</a></p