The Role of Superior Temporal Cortex in Auditory Timing

Recently, there has been upsurge of interest in the neural mechanisms of time perception. A central question is whether the representation of time is distributed over brain regions as a function of stimulus modality, task and length of the duration used or whether it is centralized in a single specific and supramodal network. The answers seem to be converging on the former, and many areas not primarily considered as temporal processing areas remain to be investigated in the temporal domain. Here we asked whether the superior temporal gyrus, an auditory modality specific area, is involved in processing of auditory timing. Repetitive transcranial magnetic stimulation was applied over left and right superior temporal gyri while participants performed either a temporal or a frequency discrimination task of single tones. A significant decrease in performance accuracy was observed after stimulation of the right superior temporal gyrus, in addition to an increase in response uncertainty as measured by the Just Noticeable Difference. The results are specific to auditory temporal processing and performance on the frequency task was not affected. Our results further support the idea of distributed temporal processing and speak in favor of the existence of modality specific temporal regions in the human brain

Controls on gut phosphatisation : the trilobites from the Weeks Formation Lagerstätte (Cambrian; Utah)

Despite being internal organs, digestive structures are frequently preserved in Cambrian Lagerstätten. However, the reasons for their fossilisation and their biological implications remain to be thoroughly explored. This is particularly true with arthropods--typically the most diverse fossilised organisms in Cambrian ecosystems--where digestive structures represent an as-yet underexploited alternative to appendage morphology for inferences on their biology. Here we describe the phosphatised digestive structures of three trilobite species from the Cambrian Weeks Formation Lagerstätte (Utah). Their exquisite, three-dimensional preservation reveals unique details on trilobite internal anatomy, such as the position of the mouth and the absence of a differentiated crop. In addition, the presence of paired pygidial organs of an unknown function is reported for the first time. This exceptional material enables exploration of the relationships between gut phosphatisation and the biology of organisms. Indeed, soft-tissue preservation is unusual in these fossils as it is restricted to the digestive structures, which indicates that the gut played a central role in its own phosphatisation. We hypothesize that the gut provided a microenvironment where special conditions could develop and harboured a source of phosphorus. The fact that gut phosphatization has almost exclusively been observed in arthropods could be explained by their uncommon ability to store ions (including phosphorous) in their digestive tissues. However, in some specimens from the Weeks Formation, the phosphatisation extends to the entire digestive system, suggesting that trilobites might have had some biological particularities not observed in modern arthropods. We speculate that one of them might have been an increased capacity for ion storage in the gut tissues, related to the moulting of their heavily-mineralised carapace

Planetary Dynamics and Habitable Planet Formation In Binary Star Systems

Whether binaries can harbor potentially habitable planets depends on several factors including the physical properties and the orbital characteristics of the binary system. While the former determines the location of the habitable zone (HZ), the latter affects the dynamics of the material from which terrestrial planets are formed (i.e., planetesimals and planetary embryos), and drives the final architecture of the planets assembly. In order for a habitable planet to form in a binary star system, these two factors have to work in harmony. That is, the orbital dynamics of the two stars and their interactions with the planet-forming material have to allow terrestrial planet formation in the habitable zone, and ensure that the orbit of a potentially habitable planet will be stable for long times. We have organized this chapter with the same order in mind. We begin by presenting a general discussion on the motion of planets in binary stars and their stability. We then discuss the stability of terrestrial planets, and the formation of potentially habitable planets in a binary-planetary system.Comment: 56 pages, 29 figures, chapter to appear in the book: Planets in Binary Star Systems (Ed. N. Haghighipour, Springer publishing company

Approaching the diagnosis of growth-restricted neonates: a cohort study

<p>Abstract</p> <p>Background</p> <p>The consequences of <it>in utero </it>growth restriction have been attracting scholarly attention for the past two decades. Nevertheless, the diagnosis of growth-restricted neonates is as yet an unresolved issue. Aim of this study is the evaluation of the performance of simple, common indicators of nutritional status, which are used in the identification of growth-restricted neonates.</p> <p>Methods</p> <p>In a cohort of 418 consecutively born term and near term neonates, four widely used anthropometric indices of body proportionality and subcutaneous fat accretion were applied, singly and in combination, as diagnostic markers for the detection of growth-restricted babies. The concordance of the indices was assessed in terms of positive and negative percent agreement and of Cohen's kappa.</p> <p>Results</p> <p>The agreement between the anthropometric indices was overall poor with a highest positive percent agreement of 62.5% and a lowest of 27.9% and the κ ranging between 0.19 and 0.58. Moreover, 6% to 32% of babies having abnormal values in just one index were apparently well-grown and the median birth weight centile of babies having abnormal values of either of two indices was found to be as high as the 46^thcentile for gestational age (95%CI 35.5 to 60.4 and 29.8 to 63.9, respectively). On the contrary, the combination of anthropometric indices appeared to have better distinguishing properties among apparently and not apparently well-grown babies. The median birth weight centile of babies having abnormal values in two (or more) indices was the 11^thcentile for gestational age (95%CI 6.3 to 16.3).</p> <p>Conclusions</p> <p>Clinical assessment and anthropometric indices in combination can define a reference standard with better performance compared to the same indices used in isolation. This approach offers an easy-to-use tool for bedside diagnosis of <it>in utero </it>growth restriction.</p

The challenges of long-term invasive mammal management: lessons from the UK

We consider the motivations, strategies, and costs involved in invasive mammal management undertaken in the UK. Widespread established invasive mammals require long‐term management to limit damage or spread, but ongoing management is costly and complex. Long‐term management is most effective where it is applied at a landscape scale, but this requires overarching co‐ordination between multiple stakeholders. Five challenges for successful long‐term management of invasive mammal species are identified as follows: defining landscape‐scale strategies, management co‐ordination, stakeholder and community engagement, sustainable funding, and evidence requirements. We make recommendations on the supportive infrastructure needed for effective landscape‐scale management of invasive mammals to fulfil long‐term conservation aims, as follows. 1. There is a need for evidence‐based Invasive Species Action Plans to provide strategy for the long‐term ongoing management of prioritised species at appropriate scales. 2. Where possible, multispecies approaches to invasive species management should be adopted. 3. Trusted leadership should be identified to take ownership of Action Plans and provide an overarching co‐ordination to bring individuals, organisations, and funders together. 4. Support for a centralised hub for training, data, and knowledge flows will greatly improve scientific outcomes through a searchable evidence base, and via best practice and knowledge sharing

Selenoether oxytocin analogues have analgesic properties in a mouse model of chronic abdominal pain

Poor oral availability and susceptibility to reduction and protease degradation is a major hurdle in peptide drug development. However, drugable receptors in the gut present an attractive niche for peptide therapeutics. Here we demonstrate, in a mouse model of chronic abdominal pain, that oxytocin receptors are significantly upregulated in nociceptors innervating the colon. Correspondingly, we develop chemical strategies to engineer non-reducible and therefore more stable oxytocin analogues. Chemoselective selenide macrocyclization yields stabilized analogues equipotent to native oxytocin. Ultra-high-field nuclear magnetic resonance structural analysis of native oxytocin and the seleno-oxytocin derivatives reveals that oxytocin has a pre-organized structure in solution, in marked contrast to earlier X-ray crystallography studies. Finally, we show that these seleno-oxytocin analogues potently inhibit colonic nociceptors both in vitro and in vivo in mice with chronic visceral hypersensitivity. Our findings have potentially important implications for clinical use of oxytocin analogues and disulphide-rich peptides in general

Phase I dose escalation and pharmacokinetic study of pluronic polymer-bound doxorubicin (SP1049C) in patients with advanced cancer

SP1049C is a novel anticancer agent containing doxorubicin and two nonionic pluronic block copolymers. In preclinical studies, SP1049C demonstrated increased efficacy compared to doxorubicin. The objectives of this first phase I study were to determine the toxicity profile, dose-limiting toxicity, maximum tolerated dose and pharmacokinetic profile of SP1049C, and to document any antitumour activity. The starting dose was 5 mg m−2 (doxorubicin content) as an intravenous infusion once every 3 weeks for up to six cycles. A total of 26 patients received 78 courses at seven dose levels. The dose-limiting toxicity was myelosuppression and DLT was reached at 90 mg m−2. The maximum tolerated dose was 70 mg m−2 and is recommended for future trials. The pharmacokinetic profile of SP1049C showed a slower clearance than has been reported for conventional doxorubicin. Evidence of antitumour activity was seen in some patients with advanced resistant solid tumours. Phase II trials with this agent are now warranted to further define its antitumour activity and safety profile

αA-Crystallin Peptide 66SDRDKFVIFLDVKHF80 Accumulating in Aging Lens Impairs the Function of α-Crystallin and Induces Lens Protein Aggregation

The eye lens is composed of fiber cells that are filled with α-, β- and γ-crystallins. The primary function of crystallins is to maintain the clarity of the lens through ordered interactions as well as through the chaperone-like function of α-crystallin. With aging, the chaperone function of α-crystallin decreases, with the concomitant accumulation of water-insoluble, light-scattering oligomers and crystallin-derived peptides. The role of crystallin-derived peptides in age-related lens protein aggregation and insolubilization is not understood.We found that αA-crystallin-derived peptide, (66)SDRDKFVIFLDVKHF(80), which accumulates in the aging lens, can inhibit the chaperone activity of α-crystallin and cause aggregation and precipitation of lens crystallins. Age-related change in the concentration of αA-(66-80) peptide was estimated by mass spectrometry. The interaction of the peptide with native crystallin was studied by multi-angle light scattering and fluorescence methods. High molar ratios of peptide-to-crystallin were favourable for aggregation and precipitation. Time-lapse recordings showed that, in the presence of αA-(66-80) peptide, α-crystallin aggregates and functions as a nucleus for protein aggregation, attracting aggregation of additional α-, β- and γ-crystallins. Additionally, the αA-(66-80) peptide shares the principal properties of amyloid peptides, such as β-sheet structure and fibril formation.These results suggest that crystallin-derived peptides such as αA-(66-80), generated in vivo, can induce age-related lens changes by disrupting the structure and organization of crystallins, leading to their insolubilization. The accumulation of such peptides in aging lenses may explain a novel mechanism for age-related crystallin aggregation and cataractogenesis

Theta-Burst Stimulation-Induced Plasticity over Primary Somatosensory Cortex Changes Somatosensory Temporal Discrimination in Healthy Humans

BACKGROUND: The somatosensory temporal discrimination threshold (STDT) measures the ability to perceive two stimuli as being sequential. Precisely how the single cerebral structures contribute in controlling the STDT is partially known and no information is available about whether STDT can be modulated by plasticity-inducing protocols. METHODOLOGY/PRINCIPAL FINDINGS: To investigate how the cortical and cerebellar areas contribute to the STDT we used transcranial magnetic stimulation and a neuronavigation system. We enrolled 18 healthy volunteers and 10 of these completed all the experimental sessions, including the control experiments. STDT was measured on the left hand before and after applying continuous theta-burst stimulation (cTBS) on the right primary somatosensory area (S1), pre-supplementary motor area (pre-SMA), right dorsolateral prefrontal cortex (DLPFC) and left cerebellar hemisphere. We then investigated whether intermittent theta-burst stimulation (iTBS) on the right S1 improved the STDT. After right S1 cTBS, STDT values increased whereas after iTBS to the same cortical site they decreased. cTBS over the DLPFC and left lateral cerebellum left the STDT statistically unchanged. cTBS over the pre-SMA also left the STDT statistically unchanged, but it increased the number of errors subjects made in distinguishing trials testing a single stimulus and those testing paired stimuli. CONCLUSIONS/SIGNIFICANCE: Our findings obtained by applying TBS to the cortical areas involved in processing sensory discrimination show that the STDT is encoded in S1, possibly depends on intrinsic S1 neural circuit properties, and can be modulated by plasticity-inducing TBS protocols delivered over S1. Our findings, giving further insight into mechanisms involved in somatosensory temporal discrimination, help interpret STDT abnormalities in movement disorders including dystonia and Parkinson's disease