5-ht inhibition of rat insulin 2 promoter cre recombinase transgene and proopiomelanocortin neuron excitability in the mouse arcuate nucleus

A number of anti-obesity agents have been developed that enhance hypothalamic 5-HT transmission. Various studies have demonstrated that arcuate neurons, which express proopiomelanocortin peptides (POMC neurons), and neuropeptide Y with agouti-related protein (NPY/AgRP) neurons, are components of the hypothalamic circuits responsible for energy homeostasis. An additional arcuate neuron population, rat insulin 2 promoter Cre recombinase transgene (RIPCre) neurons, has recently been implicated in hypothalamic melanocortin circuits involved in energy balance. It is currently unclear how 5-HT modifies neuron excitability in these local arcuate neuronal circuits. We show that 5-HT alters the excitability of the majority of mouse arcuate RIPCre neurons, by either hyperpolarization and inhibition or depolarization and excitation. RIPCre neurons sensitive to 5-HT, predominantly exhibit hyperpolarization and pharmacological studies indicate that inhibition of neuronal firing is likely to be through 5-HT1F receptors increasing current through a voltage-dependent potassium conductance. Indeed, 5-HT1F receptor immunoreactivity co-localizes with RIPCre green fluorescent protein expression. A minority population of POMC neurons also respond to 5-HT by hyperpolarization, and this appears to be mediated by the same receptor-channel mechanism. As neither POMC nor RIPCre neuronal populations display a common electrical response to 5-HT, this may indicate that sub-divisions of POMC and RIPCre neurons exist, perhaps serving different outputs

Keeping creative writing on track: Co-designing a framework to support behavior change

The application of persuasive technology in web-based and mobile phone-based systems is well established, particularly in the health domain. However, a greater understanding of the effectiveness of the techniques deployed is needed to facilitate the successful transfer of research findings into practical applications. The context explored here is that of creative writing and the potential use of persuasive technology to foster and support a productive writing routine. Employing a user-centered design approach, we conducted surveys and a co-creation workshop with writers. Goal setting and regular writing, combined with self-monitoring, were key indicators of an effective writing practice. Group and mentor support were also highlighted. Based on our findings, we developed the architecture for a mobile personal writing coach. We evaluated the architecture against existing frameworks, finding good congruence. This supports our long-term goal of creating a universal framework, applicable to a wider range of behavior change interventions, domains and users. The design considerations reported in this paper go some way towards that goal

Exchange anisotropy, disorder and frustration in diluted, predominantly ferromagnetic, Heisenberg spin systems

Motivated by the recent suggestion of anisotropic effective exchange interactions between Mn spins in Ga$_{1-x}$Mn$_x$As (arising as a result of spin-orbit coupling), we study their effects in diluted Heisenberg spin systems. We perform Monte Carlo simulations on several phenomenological model spin Hamiltonians, and investigate the extent to which frustration induced by anisotropic exchanges can reduce the low temperature magnetization in these models and the interplay of this effect with disorder in the exchange. In a model with low coordination number and purely ferromagnetic (FM) exchanges, we find that the low temperature magnetization is gradually reduced as exchange anisotropy is turned on. However, as the connectivity of the model is increased, the effect of small-to-moderate anisotropy is suppressed, and the magnetization regains its maximum saturation value at low temperatures unless the distribution of exchanges is very wide. To obtain significant suppression of the low temperature magnetization in a model with high connectivity, as is found for long-range interactions, we find it necessary to have both ferromagnetic and antiferromagnetic (AFM) exchanges (e.g. as in the RKKY interaction). This implies that disorder in the sign of the exchange interaction is much more effective in suppressing magnetization at low temperatures than exchange anisotropy.Comment: 9 pages, 8 figure

Constructing proxy records from age models (COPRA)

Reliable age models are fundamental for any palaeoclimate reconstruction. Available interpolation procedures between age control points are often inadequately reported, and very few translate age uncertainties to proxy uncertainties. Most available modeling algorithms do not allow incorporation of layer counted intervals to improve the confidence limits of the age model in question. We present a framework that allows detection and interactive handling of age reversals and hiatuses, depth-age modeling, and proxy-record reconstruction. Monte Carlo simulation and a translation procedure are used to assign a precise time scale to climate proxies and to translate dating uncertainties to uncertainties in the proxy values. The presented framework allows integration of incremental relative dating information to improve the final age model. The free software package COPRA1.0 facilitates easy interactive usage

Persistent northward North Atlantic tropical cyclone track migration over the past five centuries

Accurately predicting future tropical cyclone risk requires understanding the fundamental controls on tropical cyclone dynamics. Here we present an annually-resolved 450-year reconstruction of western Caribbean tropical cyclone activity developed using a new coupled carbon and oxygen isotope ratio technique in an exceptionally well-dated stalagmite from Belize. Western Caribbean tropical cyclone activity peaked at 1650 A.D., coincident with maximum Little Ice Age cooling, and decreased gradually until the end of the record in 1983. Considered with other reconstructions, the new record suggests that the mean track of Cape Verde tropical cyclones shifted gradually north-eastward from the western Caribbean toward the North American east coast over the last 450 years. Since ~1870 A.D., these shifts were largely driven by anthropogenic greenhouse gas and sulphate aerosol emissions. Our results strongly suggest that future emission scenarios will result in more frequent tropical cyclone impacts on the financial and population centres of the northeastern United States

Population turnover in remote oceania shortly after initial settlement

Ancient DNA from Vanuatu and Tonga dating to about 2,900–2,600 years ago (before present, BP) has revealed that the “First Remote Oceanians” associated with the Lapita archaeological culture were directly descended from the population that, beginning around 5000 BP, spread Austronesian languages from Taiwan to the Philippines, western Melanesia, and eventually Remote Oceania. Thus, ancestors of the First Remote Oceanians must have passed by the Papuan-ancestry populations they encountered in New Guinea, the Bismarck Archipelago, and the Solomon Islands with minimal admixture [1]. However, all present-day populations in Near and Remote Oceania harbor >25% Papuan ancestry, implying that additional eastward migration must have occurred. We generated genome-wide data for 14 ancient individuals from Efate and Epi Islands in Vanuatu from 2900–150 BP, as well as 185 present-day individuals from 18 islands. We find that people of almost entirely Papuan ancestry arrived in Vanuatu by around 2300 BP, most likely reflecting migrations a few hundred years earlier at the end of the Lapita period, when there is also evidence of changes in skeletal morphology and cessation of long-distance trade between Near and Remote Oceania [2, 3]. Papuan ancestry was subsequently diluted through admixture but remains at least 80%–90% in most islands. Through a fine-grained analysis of ancestry profiles, we show that the Papuan ancestry in Vanuatu derives from the Bismarck Archipelago rather than the geographically closer Solomon Islands. However, the Papuan ancestry in Polynesia—the most remote Pacific islands—derives from different sources, documenting a third stream of migration from Near to Remote Oceania

Findings from an in-depth annual tree-ring radiocarbon intercomparison

The radiocarbon (¹⁴C) calibration curve so far contains annually resolved data only for a short period of time. With accelerator mass spectrometry (AMS) matching the precision of decay counting, it is now possible to efficiently produce large datasets of annual resolution for calibration purposes using small amounts of wood. The radiocarbon intercomparison on single-year tree-ring samples presented here is the first to investigate specifically possible offsets between AMS laboratories at high precision. The results show that AMS laboratories are capable of measuring samples of Holocene age with an accuracy and precision that is comparable or even goes beyond what is possible with decay counting, even though they require a thousand times less wood. It also shows that not all AMS laboratories always produce results that are consistent with their stated uncertainties. The long-term benefits of studies of this kind are more accurate radiocarbon measurements with, in the future, better quantified uncertainties