Moving in an environment of induced sensorimotor incongruence does not influence pain sensitivity in healthy volunteers: A randomised within-subject experiment

Objectives: It has been proposed that in the same way that conflict between vestibular and visual inputs leads to motion sickness, conflict between motor commands and sensory information associated with these commands may contribute to some chronic pain states. Attempts to test this hypothesis by artificially inducing a state of sensorimotor incongruence and assessing self-reported pain have yielded equivocal results. To help clarify the effect sensorimotor incongruence has on pain we investigated the effect of moving in an environment of induced incongruence on pressure pain thresholds (PPT) and the pain experienced immediately on completion of PPT testing. Methods: Thirty-five healthy subjects performed synchronous and asynchronous upper-limb movements with and without mirror visual feedback in random order. We measured PPT over the elbow and the pain evoked by testing. Generalised linear mixed-models were performed for each outcome. Condition (four levels) and baseline values for each outcome were within-subject factors. Results: There was no effect of condition on PPT (p = 0.887) or pressure-evoked pain (p = 0.771). A sensitivity analysis using only the first PPT measure after each condition confirmed the result (p = 0.867). Discussion: Inducing a state of movement related sensorimotor incongruence in the upper-limb of healthy volunteers does not influence PPT, nor the pain evoked by testing. We found no evidence that sensorimotor incongruence upregulates the nociceptive system in healthy volunteer

Population and Environmental Correlates of Maize Yields in Mesoamerica: a Test of Boserup’s Hypothesis in the Milpa

Using a sample of 40 sources reporting milpa and mucuna-intercropped maize yields in Mesoamerica, we test Boserup’s (1965) prediction that fallow is reduced as a result of growing population density. We further examine direct and indirect effects of population density on yield. We find only mixed support for Boserupian intensification. Fallow periods decrease slightly with increasing population density in this sample, but the relationship is weak. Controlling for other covariates, fallow-unadjusted maize yields first rise then fall with population density. Fallow-adjusted maize yields peak at 390 kg/ha/yr for low population densities (8 persons / km2) and decline to around 280 kg/ha/yr for the highest population densities observed in our dataset. Fallow practices do not appear to mediate the relationship between population density and yield. The multi-level modeling methods we adopt allow for data clustering, accurate estimates of group-level variation, and they generate conditional predictions, all features essential to the comparative study of prehistoric and contemporary agricultural yields

A short history of the 5-HT2C receptor: from the choroid plexus to depression, obesity and addiction treatment

This paper is a personal account on the discovery and characterization of the 5-HT2C receptor (first known as the 5- HT1C receptor) over 30 years ago and how it translated into a number of unsuspected features for a G protein-coupled receptor (GPCR) and a diversity of clinical applications. The 5-HT2C receptor is one of the most intriguing members of the GPCR superfamily. Initially referred to as 5-HT1CR, the 5-HT2CR was discovered while studying the pharmacological features and the distribution of [3H]mesulergine-labelled sites, primarily in the brain using radioligand binding and slice autoradiography. Mesulergine (SDZ CU-085), was, at the time, best defined as a ligand with serotonergic and dopaminergic properties. Autoradiographic studies showed remarkably strong [3H]mesulergine-labelling to the rat choroid plexus. [3H]mesulergine-labelled sites had pharmacological properties different from, at the time, known or purported 5-HT receptors. In spite of similarities with 5-HT2 binding, the new binding site was called 5-HT1C because of its very high affinity for 5-HT itself. Within the following 10 years, the 5-HT1CR (later named 5- HT2C) was extensively characterised pharmacologically, anatomically and functionally: it was one of the first 5-HT receptors to be sequenced and cloned. The 5-HT2CR is a GPCR, with a very complex gene structure. It constitutes a rarity in theGPCR family: many 5-HT2CR variants exist, especially in humans, due to RNA editing, in addition to a few 5-HT2CR splice variants. Intense research led to therapeutically active 5-HT2C receptor ligands, both antagonists (or inverse agonists) and agonists: keeping in mind that a number of antidepressants and antipsychotics are 5- HT2CR antagonists/inverse agonists. Agomelatine, a 5-HT2CR antagonist is registered for the treatment of major depression. The agonist Lorcaserin is registered for the treatment of aspects of obesity and has further potential in addiction, especially nicotine/ smoking. There is good evidence that the 5-HT2CR is involved in spinal cord injury-induced spasms of the lower limbs, which can be treated with 5-HT2CR antagonists/inverse agonists such as cyproheptadine or SB206553. The 5-HT2CR may play a role in schizophrenia and epilepsy. Vabicaserin, a 5-HT2CR agonist has been in development for the treatment of schizophrenia and obesity, but was stopped. As is common, there is potential for further indications for 5-HT2CR ligands, as suggested by a number of preclinical and/or genome-wide association studies (GWAS) on depression, suicide, sexual dysfunction, addictions and obesity. The 5-HT2CR is clearly affected by a number of established antidepressants/antipsychotics and may be one of the culprits in antipsychotic-induced weight gain

Nicotinic receptors

Regulation of normal or abnormal behaviour is critically controlled by the central serotonergic systems. Recent evidence has suggested that serotonin (5-HT) neurotransmission dysfunction contributes to a variety of pathological conditions, including depression, anxiety, schizophrenia and Parkinson’s disorders. There is also a great amount of evidence indicating that 5-HT signalling may affect the reinforcing properties of drugs of abuse by the interaction and modulation of dopamine (DA) function. This chapter is focused on one of the more addictive drugs, nicotine. It is widely recognised that the effects of nicotine are strongly associated with the stimulatory action it exhibits on mesolimbic DAergic function. We outline the role of 5-HT and its plethora of receptors, focusing on 5-HT2 subtypes with relation to their involvement in the neurobiology of nicotine addiction. We also explore the novel pharmacological approaches using 5-HT agents for the treatment of nicotine dependence. Compelling evidence shows that 5-HT2C receptor agonists may be possible therapeutic targets for smoking cessation, although further investigation is required.peer-reviewe

Climate change and the rise of the central Asian Silk Roads

The final centuries BCE (Before Common Era) saw the main focus of trade between the Far East and Europe switch from the so called Northern Route across the Asian steppes to the classical silk roads. The cities across central Asia flourished and grew in size and importance. While clearly there were political, economic and cultural drivers for these changes, there may also have been a role for changes in climate in this relatively arid region of Asia. Analysis of a new ensemble of snapshot global climate model simulations, run every 250 years over the last 6000 years, allows us to assess the long term climatological changes seen across the central Asian arid region through which the classical Silk Roads run. While the climate is comparatively stable through the Holocene, the fluctuations seen in these simulations match significant cultural developments in the region. From 1500 BCE the deterioration of climate from a transient precipitation peak, along with technological development and the immigration of Aryan nomads, drove a shift towards urbanization and probably irrigation, culminating in the founding of the major cities of Bukhara and Samarkand around 700–500 BCE. Between 1000 and 250 BCE the modelled precipitation in the central Asian arid region undergoes a transition towards wetter climates. The changes in the Western Disturbances, which is the key weather system for central Asian precipitation, provides 10% more precipitation and the increased hydrological resources may provide the climatological foundation for the golden era of Silk Road trade

Downslope Transport Of Metalliferous Sediments Along The East Pacific Rise During The Late Miocene

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62932/1/316807a0.pd

Harnessing Microbially Generated Power on the Seafloor

In many marine environments, a voltage gradient exists across the water sediment interface resulting from sedimentary microbial activity. Here we show that a fuel cell consisting of an anode embedded in marine sediment and a cathode in overlying seawater can use this voltage gradient to generate electrical power in situ. Fuel cells of this design generated sustained power in a boat basin carved into a salt marsh near Tuckerton, New Jersey, and in the Yaquina Bay Estuary near Newport, Oregon. Retrieval and analysis of the Tuckerton fuel cell indicates that power generation results from at least two anode reactions: oxidation of sediment sulfide (a by-product of microbial oxidation of sedimentary organic carbon) and oxidation of sedimentary organic carbon catalyzed by microorganisms colonizing the anode. These results demonstrate in real marine environments a new form of power generation that uses an immense, renewable energy reservoir (sedimentary organic carbon) and has near-immediate application