bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in neural response to extinction recall in young adults with or without history of behavioral inhibition
Authors: Shechner Tomer , Fox Nathan A. , Mash Jamie A. , Jarcho Johanna M. , Chen Gang , Leibenluft Ellen , Pine Daniel S. , Britton Jennifer C.
Published: May 2017

Behavioral inhibition (BI) is a temperament identified in early childhood that is associated with risk for anxiety disorders, yet only about half of behaviorally inhibited children manifest anxiety later in life. We compared brain function and behavior during extinction recall in a sample of nonanxious young adults characterized in childhood with BI (n = 22) or with no BI (n = 28). Three weeks after undergoing fear conditioning and extinction, participants completed a functional magnetic resonance imaging extinction recall task assessing memory and threat differentiation for conditioned stimuli. While self-report and psychophysiological measures of differential conditioning and extinction were similar across groups, BI-related differences in brain function emerged during extinction recall. Childhood BI was associated with greater activation in subgenual anterior cingulate cortex in response to cues signaling safety. This pattern of results may reflect neural correlates that promote resilience against anxiety in a temperamentally at-risk population.
Living on Edge: New Perspectives on Anxiety, Refuge and Colonialism in Southern Africa
Authors: King Rachel
Published: May 2017

Archaeologies of colonialism have have called for exploring the culturally dynamic entanglements of people and objects while acknowledging the violence that accompanied these entanglements. Heeding these calls requires attention to how the state and state power were materialized, particularly in settler colonies where state apparatuses advanced unevenly, insidiously and clumsily. Here, I explore how the (mis)understandings and (mis)apprehensions of people and places that accompanied the halting expansion of colonial frontiers were materialized. Focusing on southern Africa's Highveld and Maloti-Drakensberg Mountains, I offer anxiety as a framework for conceiving of colonialisms as epistemic encounters: processes of ‘making sense’ of new people, things and places based on material practices, empirical experience and desire. Through a narrative of the nineteenth-century Maloti-Drakensberg told with archival, archaeological and ethnographic materials, I revisit a longstanding trope of southern African archaeology and historiography: refugia from social distress. I argue that refuge can be taken as a sense-making practice rather than as reaction to stress. I close with thoughts on what an anxiety framework can offer the still-developing field of African historical archaeology.
PRENATAL PERSONHOOD AND LIFE'S INTRINSIC VALUE: REAPPRAISING DWORKIN ON ABORTION
Authors: Greasley Kate
Published: May 2017

What is at the heart of conflict over abortion? In his celebrated contribution to the topic, Ronald Dworkin argues that disputants in the abortion debate are in fact deeply mistaken about the true terms of their disagreement. Rather than turning on the perennial question of whether or not the fetus is a person, Dworkin claims that abortion argument is, at bottom, an argument about the intrinsic value of all human life and how it is best respected. More than twenty years after Dworkin put forward his novel thesis, this article reassesses his key claims about the crux of abortion argument, partly in light of subsequent developments in the public abortion conflict. Against Dworkin's revisionist account of the abortion problem, I set out to show that his arguments do not successfully displace the primacy of the personhood question in moral and legal constitutional reasoning about abortion. Nor do they convincingly establish that prenatal personhood is not what contestants in the abortion debate are really arguing about.
Inclusion of white clover in strip-grazed perennial ryegrass swards: herbage intake and milk yield of dairy cows at different ages of sward regrowth
Authors: Ribeiro Filho H. M. N. , Delagarde R. , Peyraud J. L.
Published: May 2017

The introduction of legumes in grass-based swards provides some economic and agronomic advantages, often allowing an increase in the performance of grazing ruminants. The aim of this study was to obtain a better quantification of the nutritional benefits to dairy cows after introducing white clover into swards of perennial ryegrass (PRG), using two ages of regrowth. Four treatments were studied in a 2 ✕ 2 factorial design with two sward types and two ages of regrowth. The swards were either a pure perennial ryegrass sward with nitrogen (N) fertilization, or a perennial ryegrass/white clover mixture (GC) with no N fertilization. The regrowth ages were 19 and 35 days (treatments: PRG19, PRG35, GC19 and GC35). The proportion of clover in the GC swards was on average 420 g/kg dry matter (DM). Twelve late-lactation Holstein cows, fistulated at the rumen and duodenum, were used according to a 4 ✕ 4 Latin-square design with four 11-day periods. The pasture was strip-grazed with 12 kg DM per cow of herbage above 5 cm offered daily in all the treatments.

The effects of sward type and regrowth age were often additive, in particular for herbage intake and milk yield. Herbage organic matter (OM) intake, duodenal non-ammonia N (NAN) flow and milk yields were higher on the GC swards and lower on the older regrowths. Finally, the performance of the cows was similar on the PRG19 and GC35 treatments. The OM digestibility of the selected herbage as well as the duodenal nitrogen flux per kg digestible OM intake was not affected by the sward type. Ruminal fermentations were more intense with mixed swards and the youngest regrowths. The daily grazing time and the daily pattern of grazing activities were modified by the type of sward and by regrowth age. The average OM intake rate was higher on the GC swards than on the PRG swards. In this study, the nutritional advantage of introducing white clover into swards of perennial ryegrass was related to an increase in herbage intake and not to any improvement in the nutritive value of the sward.
Association between dietary patterns and adiposity from 4 to 7 years of age
Authors: Durão Catarina , Severo Milton , Oliveira Andreia , Moreira Pedro , Guerra António , Barros Henrique , Lopes Carla
Published: May 2017

Objective

The present study aimed to evaluate the association of 4-year-old children’s dietary patterns with adiposity at 7 years, according to child’s sex, using a conceptual model.

Design

Prospective cohort study. Diet was assessed using an FFQ. Age- and sex-specific BMI standard deviation scores (Z-scores) were defined according to the WHO. Fat mass percentage (FM%), fat mass index (FMI) and waist-to-height ratio (WHtR) were also considered, converted into Z-scores using sex-specific means and standard deviations of the current sample. Dietary patterns were identified by latent class analysis and their association with adiposity was estimated by linear regression models.

Setting

Population-based birth cohort Generation XXI (Porto, Portugal, 2005–2006).

Subjects

Children (n 3473) evaluated at both 4 and 7 years of age.

Results

Three dietary patterns were identified: high in energy-dense foods (EDF); low in foods typically consumed at main meals and intermediate in snacks (Snacking); and higher in vegetables and fish and lower in EDF (Healthier, reference). The EDF dietary pattern at 4 years of age was positively associated with later BMI only in girls (β=0·075, 95 % CI 0·009, 0·140, P-interaction=0·046). The EDF dietary pattern was also associated with other adiposity indicators only in girls (FMI: β=0·071, 95 % CI 0·000, 0·142; WHtR: β=0·094, 95 % CI 0·023, 0·164). Snacking was not significantly associated with any marker of adiposity in either girls or boys.

Conclusions

Although dietary patterns and adiposity persisted across the two ages in both sexes, EDF at 4 years of age increased adiposity at 7 years of age only in girls.
The epigenetic effects of assisted reproductive technologies: ethical considerations
Authors: Roy M.-C. , Dupras C. , Ravitsky V.
Published: May 2017

The use of assisted reproductive technologies (ART) has increased significantly, allowing many coping with infertility to conceive. However, an emerging body of evidence suggests that ART could carry epigenetic risks for those conceived through the use of these technologies. In accordance with the Developmental Origins of Health and Disease hypothesis, ART could increase the risk of developing late-onset diseases through epigenetic mechanisms, as superovulation, fertilization methods and embryo culture could impair the embryo’s epigenetic reprogramming. Such epigenetic risks raise ethical issues for all stakeholders: prospective parents and children, health professionals and society. This paper focuses on ethical issues raised by the consideration of these risks when using ART. We apply two key ethical principles of North American bioethics (respect for autonomy and non-maleficence) and suggest that an ethical tension may emerge from conflicting duties to promote the reproductive autonomy of prospective parents on one hand, and to minimize risks to prospective children on the other. We argue that this tension is inherent to the entire enterprise of ART and thus cannot be addressed by individual clinicians in individual cases. We also consider the implications of the ‘non-identity problem’ in this context. We call for additional research that would allow a more robust evidence base for policy. We also call upon professional societies to provide clinicians with guidelines and educational resources to facilitate the communication of epigenetic risks associated with ART to patients, taking into consideration the challenges of communicating risk information whose validity is still uncertain.
A tale of two risks: smoking, diabetes and the subgingival microbiome
Authors: Ganesan Sukirth M , Joshi Vinayak , Fellows Megan , Dabdoub Shareef M , Nagaraja Haikady N , O’Donnell Benjamin , Deshpande Neeta Rohit , Kumar Purnima S
Published: May 2017

Although smoking and diabetes have been established as the only two risk factors for periodontitis, their individual and synergistic impacts on the periodontal microbiome are not well studied. The present investigation analyzed 2.7 million 16S sequences from 175 non-smoking normoglycemic individuals (controls), smokers, diabetics and diabetic smokers with periodontitis as well as periodontally healthy controls, smokers and diabetics to assess subgingival bacterial biodiversity and co-occurrence patterns. The microbial signatures of periodontally healthy smokers, but not diabetics, were highly aligned with the disease-associated microbiomes of their respective cohorts. Diabetics were dominated by species belonging to Fusobacterium, Parvimonas, Peptostreptococcus, Gemella, Streptococcus, Leptotrichia, Filifactor, Veillonella, TM7 and Terrahemophilus. These microbiomes exhibited significant clustering based on HbA1c levels (pre-diabetic (<6.5%), diabetic (6.5–9.9%), diabetics >10%). Smokers with periodontitis evidenced a robust core microbiome (species identified in at least 80% of individuals) dominated by anaerobes, with inter-individual differences attributable largely to the ‘rare biosphere’. Diabetics and diabetic smokers, on the other hand, were microbially heterogeneous and enriched for facultative species. In smokers, microbial co-occurrence networks were sparse and predominantly congeneric, while robust inter-generic networks were observed in diabetics and diabetic smokers. Smoking and hyperglycemia impact the subgingival microbiome in distinct ways, and when these perturbations intersect, their synergistic effect is greater than what would be expected from the sum of each effect separately. Thus, this study underscores the importance of early intervention strategies in maintaining health-compatible microbiomes in high-risk individuals, as well as the need to personalize these interventions based on the environmental perturbation.
Light enhances the growth rates of natural populations of aerobic anoxygenic phototrophic bacteria
Authors: Ferrera Isabel , Sánchez Olga , Kolářová Eva , Koblížek Michal , Gasol Josep M
Published: May 2017

Aerobic anoxygenic phototrophic (AAP) bacteria are microorganisms that can harvest light energy using bacteriochlorophyll a to supplement their predominantly organotrophic metabolism. Growth enhancement by light has repeatedly been demonstrated in laboratory experiments with AAP isolates. However, the ecological advantage of light utilization is unclear, as it has never been proven in the natural environment. Here, we conducted manipulation experiments in the NW Mediterranean and found that AAP bacteria display high growth rates which are controlled to a large extent by intense grazing pressure and phosphorous availability. Foremost, we found that, contrarily to the bulk bacterioplakton, AAP bacteria display higher growth rates when incubated under light-dark cycles than in complete darkness. These results represent the first direct evidence that natural populations of marine AAP bacteria can be stimulated by light.
Proteomic analysis of JAK2V617F-induced changes identifies potential new combinatorial therapeutic approaches
Authors: Pearson S , Williamson A J K , Blance R , Somervaille T C P , Taylor S , Azadbakht N , Whetton A D , Pierce A
Published: May 2017

In excess of 90% of patients with polycythaemia vera (PV) express a mutated form of Janus kinase 2 (JAK2), JAK2V617F. Such aberrant proteins offer great potential for the treatment of these diseases; however, inhibitors to JAK2 have had limited success in the clinic in terms of curing the disease. To understand the effects of this oncogene in haematopoietic cells with the aim of improving treatment strategies, we undertook a systematic evaluation of the effects of JAK2V617F expression using proteomics. The effects of JAK2V617F on over 5000 proteins and 2000 nuclear phosphopeptide sites were relatively quantified using either SILAC or eight-channel iTRAQ mass spectrometry. Pathway analysis of the proteins identified as changing indicated disruption to the p53 and MYC signalling pathways. These changes were confirmed using orthogonal approaches. The insight gained from this proteomic analysis led to the formation of hypothesis-driven analysis on inhibitor-mediated effects on primary cells from patients with a JAK2V617F mutation. Simultaneous inhibition of MYC and upregulation of p53 led to the preferential extinction of JAK2V617F-positive CD34+ cells, illustrating a potential therapeutic benefit from combined targeting of p53 and MYC.
Impact of fat mass and distribution on lipid turnover in human adipose tissue
Authors: Spalding Kirsty L. , Bernard Samuel , Näslund Erik , Salehpour Mehran , Possnert Göran , Appelsved Lena , Fu Keng-Yeh , Alkass Kanar , Druid Henrik , Thorell Anders , Rydén Mikael , Arner Peter
Published: May 2017

Differences in white adipose tissue (WAT) lipid turnover between the visceral (vWAT) and subcutaneous (sWAT) depots may cause metabolic complications in obesity. Here we compare triglyceride age and, thereby, triglyceride turnover in vWAT and sWAT biopsies from 346 individuals and find that subcutaneous triglyceride age and storage capacity are increased in overweight or obese individuals. Visceral triglyceride age is only increased in excessively obese individuals and associated with a lower lipid removal capacity. Thus, although triglyceride storage capacity in sWAT is higher than in vWAT, the former plateaus at substantially lower levels of excess WAT mass than vWAT. In individuals with central or visceral obesity, lipid turnover is selectively increased in vWAT. Obese individuals classified as ‘metabolically unhealthy’ (according to ATPIII criteria) who have small subcutaneous adipocytes exhibit reduced triglyceride turnover. We conclude that excess WAT results in depot-specific differences in lipid turnover and increased turnover in vWAT and/or decreased turnover in sWAT may result in metabolic complications of overweight or obesity.
Cis-perturbation of cancer drivers by the HTLV-1/BLV proviruses is an early determinant of leukemogenesis
Authors: Rosewick Nicolas , Durkin Keith , Artesi Maria , Marçais Ambroise , Hahaut Vincent , Griebel Philip , Arsic Natasa , Avettand-Fenoel Véronique , Burny Arsène , Charlier Carole , Hermine Olivier , Georges Michel , Van den Broeke Anne
Published: May 2017

Human T-cell leukaemia virus type-1 (HTLV-1) and bovine leukaemia virus (BLV) infect T- and B-lymphocytes, respectively, provoking a polyclonal expansion that will evolve into an aggressive monoclonal leukaemia in ∼5% of individuals following a protracted latency period. It is generally assumed that early oncogenic changes are largely dependent on virus-encoded products, especially TAX and HBZ, while progression to acute leukaemia/lymphoma involves somatic mutations, yet that both are independent of proviral integration site that has been found to be very variable between tumours. Here, we show that HTLV-1/BLV proviruses are integrated near cancer drivers which they affect either by provirus-dependent transcription termination or as a result of viral antisense RNA-dependent cis-perturbation. The same pattern is observed at polyclonal non-malignant stages, indicating that provirus-dependent host gene perturbation contributes to the initial selection of the multiple clones characterizing the asymptomatic stage, requiring additional alterations in the clone that will evolve into full-blown leukaemia/lymphoma.
Time-compressed preplay of anticipated events in human primary visual cortex
Authors: Ekman Matthias , Kok Peter , de Lange Floris P.
Published: May 2017

Perception is guided by the anticipation of future events. It has been hypothesized that this process may be implemented by pattern completion in early visual cortex, in which a stimulus sequence is recreated after only a subset of the visual input is provided. Here we test this hypothesis using ultra-fast functional magnetic resonance imaging to measure BOLD activity at precisely defined receptive field locations in visual cortex (V1) of human volunteers. We find that after familiarizing subjects with a spatial sequence, flashing only the starting point of the sequence triggers an activity wave in V1 that resembles the full stimulus sequence. This preplay activity is temporally compressed compared to the actual stimulus sequence and remains present even when attention is diverted from the stimulus sequence. Preplay might therefore constitute an automatic prediction mechanism for temporal sequences in V1.
Observed variations in U.S. frost timing linked to atmospheric circulation patterns
Authors: Strong Courtenay , McCabe Gregory J.
Published: May 2017

Several studies document lengthening of the frost-free season within the conterminous United States (U.S.) over the past century, and report trends in spring and fall frost timing that could stem from hemispheric warming. In the absence of warming, theory and case studies link anomalous frost timing to atmospheric circulation anomalies. However, recent efforts to relate a century of observed changes in U.S. frost timing to various atmospheric circulations yielded only modest correlations, leaving the relative importance of circulation and warming unclear. Here, we objectively partition the U.S. into four regions and uncover atmospheric circulations that account for 25–48% of spring and fall-frost timing. These circulations appear responsive to historical warming, and they consistently account for more frost timing variability than hemispheric or regional temperature indices. Reliable projections of future variations in growing season length depend on the fidelity of these circulation patterns in global climate models.
Quantifying similarity of pore-geometry in nanoporous materials
Authors: Lee Yongjin , Barthel Senja D. , Dłotko Paweł , Moosavi S. Mohamad , Hess Kathryn , Smit Berend
Published: May 2017

In most applications of nanoporous materials the pore structure is as important as the chemical composition as a determinant of performance. For example, one can alter performance in applications like carbon capture or methane storage by orders of magnitude by only modifying the pore structure. For these applications it is therefore important to identify the optimal pore geometry and use this information to find similar materials. However, the mathematical language and tools to identify materials with similar pore structures, but different composition, has been lacking. We develop a pore recognition approach to quantify similarity of pore structures and classify them using topological data analysis. This allows us to identify materials with similar pore geometries, and to screen for materials that are similar to given top-performing structures. Using methane storage as a case study, we also show that materials can be divided into topologically distinct classes requiring different optimization strategies.
Two forms of death in ageing Caenorhabditis elegans
Authors: Zhao Yuan , Gilliat Ann F. , Ziehm Matthias , Turmaine Mark , Wang Hongyuan , Ezcurra Marina , Yang Chenhao , Phillips George , McBay David , Zhang William B. , Partridge Linda , Pincus Zachary , Gems David
Published: May 2017

Ageing generates senescent pathologies, some of which cause death. Interventions that delay or prevent lethal pathologies will extend lifespan. Here we identify life-limiting pathologies inCaenorhabditis eleganswith a necropsy analysis of worms that have died of old age. Our results imply the presence of multiple causes of death. Specifically, we identify two classes of corpse: early deaths with a swollen pharynx (which we call ‘P deaths’), and later deaths with an atrophied pharynx (termed ‘p deaths’). The effects of interventions on lifespan can be broken down into changes in the frequency and/or timing of either form of death. For example,glp-1mutation only delays p death, whileeat-2mutation reduces P death. Combining pathology and mortality analysis allows mortality profiles to be deconvolved, providing biological meaning to complex survival and mortality profiles.
Efficient protein production inspired by how spiders make silk
Authors: Kronqvist Nina , Sarr Médoune , Lindqvist Anton , Nordling Kerstin , Otikovs Martins , Venturi Luca , Pioselli Barbara , Purhonen Pasi , Landreh Michael , Biverstål Henrik , Toleikis Zigmantas , Sjöberg Lisa , Robinson Carol V. , Pelizzi Nicola , Jörnvall Hans , Hebert Hans , Jaudzems Kristaps , Curstedt Tore , Rising Anna , Johansson Jan
Published: May 2017

Membrane proteins are targets of most available pharmaceuticals, but they are difficult to produce recombinantly, like many other aggregation-prone proteins. Spiders can produce silk proteins at huge concentrations by sequestering their aggregation-prone regions in micellar structures, where the very soluble N-terminal domain (NT) forms the shell. We hypothesize that fusion to NT could similarly solubilize non-spidroin proteins, and design a charge-reversed mutant (NT*) that is pH insensitive, stabilized and hypersoluble compared to wild-type NT. NT*-transmembrane protein fusions yield up to eight times more of soluble protein in Escherichia coli than fusions with several conventional tags. NT* enables transmembrane peptide purification to homogeneity without chromatography and manufacture of low-cost synthetic lung surfactant that works in an animal model of respiratory disease. NT* also allows efficient expression and purification of non-transmembrane proteins, which are otherwise refractory to recombinant production, and offers a new tool for reluctant proteins in general.
Airborne observations reveal elevational gradient in tropical forest isoprene emissions
Authors: Gu Dasa , Guenther Alex B. , Shilling John E. , Yu Haofei , Huang Maoyi , Zhao Chun , Yang Qing , Martin Scot T. , Artaxo Paulo , Kim Saewung , Seco Roger , Stavrakou Trissevgeni , Longo Karla M. , Tóta Julio , de Souza Rodrigo Augusto Ferreira , Vega Oscar , Liu Ying , Shrivastava Manish , Alves Eliane G. , Santos Fernando C. , Leng Guoyong , Hu Zhiyuan
Published: May 2017

Isoprene dominates global non-methane volatile organic compound emissions, and impacts tropospheric chemistry by influencing oxidants and aerosols. Isoprene emission rates vary over several orders of magnitude for different plants, and characterizing this immense biological chemodiversity is a challenge for estimating isoprene emission from tropical forests. Here we present the isoprene emission estimates from aircraft eddy covariance measurements over the Amazonian forest. We report isoprene emission rates that are three times higher than satellite top-down estimates and 35% higher than model predictions. The results reveal strong correlations between observed isoprene emission rates and terrain elevations, which are confirmed by similar correlations between satellite-derived isoprene emissions and terrain elevations. We propose that the elevational gradient in the Amazonian forest isoprene emission capacity is determined by plant species distributions and can substantially explain isoprene emission variability in tropical forests, and use a model to demonstrate the resulting impacts on regional air quality.
Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1
Authors: Morland Cecilie , Andersson Krister A. , Haugen Øyvind P. , Hadzic Alena , Kleppa Liv , Gille Andreas , Rinholm Johanne E. , Palibrk Vuk , Diget Elisabeth H. , Kennedy Lauritz H. , Stølen Tomas , Hennestad Eivind , Moldestad Olve , Cai Yiqing , Puchades Maja , Offermanns Stefan , Vervaeke Koen , Bjørås Magnar , Wisløff Ulrik , Storm-Mathisen Jon , Bergersen Linda H.
Published: May 2017

Physical exercise can improve brain function and delay neurodegeneration; however, the initial signal from muscle to brain is unknown. Here we show that the lactate receptor (HCAR1) is highly enriched in pial fibroblast-like cells that line the vessels supplying blood to the brain, and in pericyte-like cells along intracerebral microvessels. Activation of HCAR1 enhances cerebral vascular endothelial growth factor A (VEGFA) and cerebral angiogenesis. High-intensity interval exercise (5 days weekly for 7 weeks), as well as L-lactate subcutaneous injection that leads to an increase in blood lactate levels similar to exercise, increases brain VEGFA protein and capillary density in wild-type mice, but not in knockout mice lacking HCAR1. In contrast, skeletal muscle shows no vascular HCAR1 expression and no HCAR1-dependent change in vascularization induced by exercise or lactate. Thus, we demonstrate that a substance released by exercising skeletal muscle induces supportive effects in brain through an identified receptor.
Correction: Corrigendum: An extra-uterine system to physiologically support the extreme premature lamb
Authors: Partridge Emily A. , Davey Marcus G. , Hornick Matthew A. , McGovern Patrick E. , Mejaddam Ali Y. , Vrecenak Jesse D. , Mesas-Burgos Carmen , Olive Aliza , Caskey Robert C. , Weiland Theodore R. , Han Jiancheng , Schupper Alexander J. , Connelly James T. , Dysart Kevin C. , Rychik Jack , Hedrick Holly L. , Peranteau William H. , Flake Alan W.
Published: May 2017

Nature Communications 8: Article number: 15112 (2017); Published 25 April 2017; Updated 23 May 2017 A patent based on the work reported in this Article was inadvertently omitted from the Competing interests section of this article. The Competing interests statement should read: E.M., A.F. and M.D. are co-authors on a patent entitled ‘Extracorporeal life support system and methods of use thereof’ (Patent no.
The relation between human hair follicle density and touch perception
Authors: Jönsson Emma H. , Bendas Johanna , Weidner Kerstin , Wessberg Johan , Olausson Håkan , Wasling Helena Backlund , Croy Ilona
Published: May 2017

Unmyelinated low threshold C-tactile fibers moderate pleasant aspects of touch. These fibers respond optimally to stroking stimulation of the skin with slow velocities (1–10 cm/s). Low threshold mechanoreceptors are arranged around hair follicles in rodent skin. If valid also in humans, hair follicle density (HFD) may relate to the perceived pleasantness of stroking tactile stimulation. We conducted two studies that examined the relation between HFD and affective touch perception in humans. In total, 138 healthy volunteers were stroked on the forearm and rated the pleasantness and intensity. Stimulation was performed by a robotic tactile stimulator delivering C-tactile optimal (1, 3, 10 cm/s) and non-optimal (0.1, 0.3, 30 cm/s) stroking velocities. Additionally, a measure of discriminative touch was applied in study 2. HFD of the same forearm was determined using the Cyanoacrylate Skin Stripping Method (CSSM), which we validated in a pretest. Women had higher HFD than men, which was explained by body size and weight. Furthermore, women rated affective touch stimuli as more pleasant and had higher tactile acuity. Depilation did not affect touch perception. A weak relationship was found between the C-tactile specific aspects of affective touch perception and HFD, and the hypothesis of HFD relating to pleasant aspects of stroking only received weak support.
Working Memory Requires a Combination of Transient and Attractor-Dominated Dynamics to Process Unreliably Timed Inputs
Authors: Nachstedt Timo , Tetzlaff Christian
Published: May 2017

Working memory stores and processes information received as a stream of continuously incoming stimuli. This requires accurate sequencing and it remains puzzling how this can be reliably achieved by the neuronal system as our perceptual inputs show a high degree of temporal variability. One hypothesis is that accurate timing is achieved by purely transient neuronal dynamics; by contrast a second hypothesis states that the underlying network dynamics are dominated by attractor states. In this study, we resolve this contradiction by theoretically investigating the performance of the system using stimuli with differently accurate timing. Interestingly, only the combination of attractor and transient dynamics enables the network to perform with a low error rate. Further analysis reveals that the transient dynamics of the system are used to process information, while the attractor states store it. The interaction between both types of dynamics yields experimentally testable predictions and we show that this way the system can reliably interact with a timing-unreliable Hebbian-network representing long-term memory. Thus, this study provides a potential solution to the long-standing problem of the basic neuronal dynamics underlying working memory.
Requirement for Jagged1-Notch2 signaling in patterning the bones of the mouse and human middle ear
Authors: Teng Camilla S. , Yen Hai-Yun , Barske Lindsey , Smith Bea , Llamas Juan , Segil Neil , Go John , Sanchez-Lara Pedro A. , Maxson Robert E. , Crump J. Gage
Published: May 2017

Whereas Jagged1-Notch2 signaling is known to pattern the sensorineural components of the inner ear, its role in middle ear development has been less clear. We previously reported a role for Jagged-Notch signaling in shaping skeletal elements derived from the first two pharyngeal arches of zebrafish. Here we show a conserved requirement for Jagged1-Notch2 signaling in patterning the stapes and incus middle ear bones derived from the equivalent pharyngeal arches of mammals. Mice lacking Jagged1 or Notch2 in neural crest-derived cells (NCCs) of the pharyngeal arches display a malformed stapes. Heterozygous Jagged1 knockout mice, a model for Alagille Syndrome (AGS), also display stapes and incus defects. We find that Jagged1-Notch2 signaling functions early to pattern the stapes cartilage template, with stapes malformations correlating with hearing loss across all frequencies. We observe similar stapes defects and hearing loss in one patient with heterozygous JAGGED1 loss, and a diversity of conductive and sensorineural hearing loss in nearly half of AGS patients, many of which carry JAGGED1 mutations. Our findings reveal deep conservation of Jagged1-Notch2 signaling in patterning the pharyngeal arches from fish to mouse to man, despite the very different functions of their skeletal derivatives in jaw support and sound transduction.
Characterization of meta-Cresol Purple for spectrophotometric pH measurements in saline and hypersaline media at sub-zero temperatures
Authors: Loucaides Socratis , Rèrolle Victoire M. C. , Papadimitriou Stathys , Kennedy Hilary , Mowlem Matthew C. , Dickson Andrew G. , Gledhill Martha , Achterberg Eric P.
Published: May 2017

Accurate pH measurements in polar waters and sea ice brines require pH indicator dyes characterized at near-zero and below-zero temperatures and high salinities. We present experimentally determined physical and chemical characteristics of purified meta-Cresol Purple (mCP) pH indicator dye suitable for pH measurements in seawater and conservative seawater-derived brines at salinities (S) between 35 and 100 and temperatures (T) between their freezing point and 298.15 K (25 °C). Within this temperature and salinity range, using purified mCP and a novel thermostated spectrophotometric device, the pH on the total scale (pHT) can be calculated from direct measurements of the absorbance ratio R of the dye in natural samples as$${\boldsymbol{p}}{{\boldsymbol{H}}}_{{\boldsymbol{T}}}{\boldsymbol{=}}{\boldsymbol{-}}{\bf{log}}({{\boldsymbol{k}}}_{{\bf{2}}}^{{\boldsymbol{T}}}{{\boldsymbol{e}}}_{{\bf{2}}}){\boldsymbol{+}}\,{\bf{log}}(\frac{{\boldsymbol{R}}{\boldsymbol{-}}{{\boldsymbol{e}}}_{{\bf{1}}}}{{\bf{1}}{\boldsymbol{-}}{\boldsymbol{R}}\frac{{{\boldsymbol{e}}}_{{\bf{3}}}}{{{\boldsymbol{e}}}_{{\bf{2}}}}})$$
p

H

T

=
−

log

(

k

2

T

e

2

)

+

log

(

R
−

e

1

1
−
R

e

3

e

2

)

Based on the mCP characterization in these extended conditions, the temperature and salinity dependence of the molar absorptivity ratios and − $${\bf{log}}({{\boldsymbol{k}}}_{{\bf{2}}}^{{\boldsymbol{T}}}{{\boldsymbol{e}}}_{{\bf{2}}})$$
log

(

k

2

T

e

2

)

of purified mCP is described by the following functions: e1 = −0.004363 + 3.598 × 10−5T, e3/e2 = −0.016224 + 2.42851 × 10−4T + 5.05663 × 10−5(S − 35), and − $${\bf{log}}({{\boldsymbol{k}}}_{{\bf{2}}}^{{\boldsymbol{T}}}{{\boldsymbol{e}}}_{{\bf{2}}})$$
log

(

k

2

T

e

2

)

= −319.8369 + 0.688159 S −0.00018374 S2 + (10508.724 − 32.9599 S + 0.059082S2) T−1 + (55.54253 − 0.101639 S) ln T −0.08112151T. This work takes the characterisation of mCP beyond the currently available ranges of 278.15 K ≤ T ≤ 308.15 K and 20 ≤ S ≤ 40 in natural seawater, thereby allowing high quality pHT measurements in polar systems.
Glycogen synthase kinase 3β inhibitors prevent hepatitis C virus release/assembly through perturbation of lipid metabolism
Authors: Sarhan Mohammed A. , Abdel-Hakeem Mohamed S. , Mason Andrew L. , Tyrrell D. Lorne , Houghton Michael
Published: May 2017

Direct acting antivirals against hepatitis C virus (HCV) have markedly improved cure rates in the past few years. However, they are expensive, with only few targeting host cell factors, and affecting virus assembly and release. Huh7.5 cells infected with a JFH-1 clone of HCV were treated with two different glycogen synthase kinase (GSK3)-β inhibitors; AR-A014418 and lithium chloride. Intra- and extracellular HCV virions and specific infectivity was determined using real-time RT-PCR and TCID50, and changes in lipid production were identified by enzyme-linked immunoassay and mass spectrometry analyses. Similarly, effect on two HCV replicon cells were identified by the luciferase activity. Although there was limited effect on virus replication in Huh7.5 cells and replicons, Huh7.5 cells treated with GSK3β inhibitors produced significantly less viral particles in comparison to untreated cells. In addition, the treated cells synthesized significantly lower amounts of ApoB and trapped the ApoE lipoproteins in the cells. In conclusion, our study suggests that GSK3β plays a pivotal role in HCV virion assembly and release mediated in part through inhibition of apolipoprotein synthesis.
Merlin is required for coordinating proliferation of two stem cell lineages in the Drosophila testis
Authors: Inaba Mayu , Sorenson Dorothy R. , Kortus Matt , Salzmann Viktoria , Yamashita Yukiko M.
Published: May 2017

Although the mechanisms that balance self-renewal and differentiation of a stem cell lineage have been extensively studied, it remains poorly understood how tissues that contain multiple stem cell lineages maintain balanced proliferation among distinct lineages: when stem cells of a particular lineage proliferate, how do the other lineages respond to maintain the correct ratio of cells among linages? Here, we show that Merlin (Mer), a homolog of the human tumor suppressor neurofibromatosis 2, is required to coordinate proliferation of germline stem cells (GSCs) and somatic cyst stem cells (CySCs) in the Drosophila testis. Mer mutant CySCs fail to coordinate their proliferation with that of GSCs in multiple settings, and can be triggered to undergo tumorous overproliferation. Mer executes its function by stabilizing adherens junctions. Given the known role of Mer in contact-dependent inhibition of proliferation, we propose that the proliferation of CySCs are regulated by crowdedness, or confluency, of cells in their lineage with respect to that of germline, thereby coordinating the proliferation of two lineages.
A new, long-term daily satellite-based rainfall dataset for operational monitoring in Africa
Authors: Maidment Ross I , Grimes David , Black Emily , Tarnavsky Elena , Young Matthew , Greatrex Helen , Allan Richard P , Stein Thorwald , Nkonde Edson , Senkunda Samuel , Alcántara Edgar Misael Uribe
Published: May 2017

Rainfall information is essential for many applications in developing countries, and yet, continually updated information at fine temporal and spatial scales is lacking. In Africa, rainfall monitoring is particularly important given the close relationship between climate and livelihoods. To address this information gap, this paper describes two versions (v2.0 and v3.0) of the TAMSAT daily rainfall dataset based on high-resolution thermal-infrared observations, available from 1983 to the present. The datasets are based on the disaggregation of 10-day (v2.0) and 5-day (v3.0) total TAMSAT rainfall estimates to a daily time-step using daily cold cloud duration. This approach provides temporally consistent historic and near-real time daily rainfall information for all of Africa. The estimates have been evaluated using ground-based observations from five countries with contrasting rainfall climates (Mozambique, Niger, Nigeria, Uganda, and Zambia) and compared to other satellite-based rainfall estimates. The results indicate that both versions of the TAMSAT daily estimates reliably detects rainy days, but have less skill in capturing rainfall amount—results that are comparable to the other datasets.
Advancing Precambrian palaeomagnetism with the PALEOMAGIA and PINT(QPI) databases
Authors: Veikkolainen Toni H. , Biggin Andrew J. , Pesonen Lauri J. , Evans David A. , Jarboe Nicholas A.
Published: May 2017

State-of-the-art measurements of the direction and intensity of Earth’s ancient magnetic field have made important contributions to our understanding of the geology and palaeogeography of Precambrian Earth. The PALEOMAGIA and PINT(QPI) databases provide thorough public collections of important palaeomagnetic data of this kind. They comprise more than 4,100 observations in total and have been essential in supporting our international collaborative efforts to understand Earth's magnetic history on a timescale far longer than that of the present Phanerozoic Eon. Here, we provide an overview of the technical structure and applications of both databases, paying particular attention to recent improvements and discoveries.
Unique identifiers for small molecules enable rigorous labeling of their atoms
Authors: Dashti Hesam , Westler William M. , Markley John L. , Eghbalnia Hamid R.
Published: May 2017

Rigorous characterization of small organic molecules in terms of their structural and biological properties is vital to biomedical research. The three-dimensional structure of a molecule, its ‘photo ID’, is inefficient for searching and matching tasks. Instead, identifiers play a key role in accessing compound data. Unique and reproducible molecule and atom identifiers are required to ensure the correct cross-referencing of properties associated with compounds archived in databases. The best approach to this requirement is the International Chemical Identifier (InChI). However, the current implementation of InChI fails to provide a complete standard for atom nomenclature, and incorrect use of the InChI standard has resulted in the proliferation of non-unique identifiers. We propose a methodology and associated software tools, named ALATIS, that overcomes these shortcomings. ALATIS is an adaptation of InChI, which operates fully within the InChI convention to provide unique and reproducible molecule and all atom identifiers. ALATIS includes an InChI extension for unique atom labeling of symmetric molecules. ALATIS forms the basis for improving reproducibility and unifying cross-referencing across databases.
Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial
Authors: Quintana D S , Westlye L T , Hope S , Nærland T , Elvsåshagen T , Dørum E , Rustan Ø , Valstad M , Rezvaya L , Lishaugen H , Stensønes E , Yaqub S , Smerud K T , Mahmoud R A , Djupesland P G , Andreassen O A
Published: May 2017

The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin’s dose–response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequence of single-dose sessions, 17 male adults with ASD received 8 international units (IU) oxytocin, 24IU oxytocin or placebo followed by four social-cognitive tasks. We observed an omnibus main effect of treatment on the primary outcome measure of overt emotion salience as measured by emotional ratings of faces (η2=0.18). Compared to placebo, 8IU treatment increased overt emotion salience (P=0.02, d=0.63). There was no statistically significant increase after 24IU treatment (P=0.12, d=0.4). The effects after 8IU oxytocin were observed despite no significant increase in peripheral blood plasma oxytocin concentrations. We found no significant effects for reading the mind in the eyes task performance or secondary outcome social-cognitive tasks (emotional dot probe and face-morphing). To our knowledge, this is the first trial to assess the dose-dependent effects of a single oxytocin administration in autism, with results indicating that a low dose of oxytocin can significantly modulate overt emotion salience despite minimal systemic exposure.
Shifting brain inhibitory balance and connectivity of the prefrontal cortex of adults with autism spectrum disorder
Authors: Ajram L A , Horder J , Mendez M A , Galanopoulos A , Brennan L P , Wichers R H , Robertson D M , Murphy C M , Zinkstok J , Ivin G , Heasman M , Meek D , Tricklebank M D , Barker G J , Lythgoe D J , Edden R A E , Williams S C , Murphy D G M , McAlonan G M
Published: May 2017

Currently, there are no effective pharmacologic treatments for the core symptoms of autism spectrum disorder (ASD). There is, nevertheless, potential for progress. For example, recent evidence suggests that the excitatory (E) glutamate and inhibitory (I) GABA systems may be altered in ASD. However, no prior studies of ASD have examined the ‘responsivity’ of the E–I system to pharmacologic challenge; or whether E–I modulation alters abnormalities in functional connectivity of brain regions implicated in the disorder. Therefore, we used magnetic resonance spectroscopy ([1H]MRS) to measure prefrontal E–I flux in response to the glutamate and GABA acting drug riluzole in adult men with and without ASD. We compared the change in prefrontal ‘Inhibitory Index’—the GABA fraction within the pool of glutamate plus GABA metabolites—post riluzole challenge; and the impact of riluzole on differences in resting-state functional connectivity. Despite no baseline differences in E–I balance, there was a significant group difference in response to pharmacologic challenge. Riluzole increased the prefrontal cortex inhibitory index in ASD but decreased it in controls. There was also a significant group difference in prefrontal functional connectivity at baseline, which was abolished by riluzole within the ASD group. Our results also show, for we believe the first time in ASD, that E–I flux can be ‘shifted’ with a pharmacologic challenge, but that responsivity is significantly different from controls. Further, our initial evidence suggests that abnormalities in functional connectivity can be ‘normalised’ by targeting E–I, even in adults.
Non-biological reduction of Cr(vi) by reacting with humic acids composted from cattle manure
Authors: Wu Min , Li Gongxia , Jiang Xiaolin , Xiao Qianqian , Niu Mingxing , Wang Zhiyuan , Wang Yayi
Published: May 2017

Previous studies on reduction of Cr(vi) by humic acids (HAs) have seldom used the extracts from composted animal manure.
Nanomaterials engineering for drug delivery: a hybridization approach
Authors: Mohammadi M. Rezaa , Nojoomi Amirali , Mozafari Masoud , Dubnika Arita , Inayathullah Mohammed , Rajadas Jayakumar
Published: May 2017

Nanoscale hybridization to fabricate all-in-one nanoparticles for superior targeted delivery systems.
Formation of (PNP)Rh complexes containing covalent rhodium–zinc bonds in studies of potential Rh-catalysed Negishi coupling
Authors: Pell Christopher J. , Shih Wei-Chun , Gatard Sylvain , Ozerov Oleg V.
Published: May 2017

While investigating rhodium-catalyzed Negishi coupling, it was observed that the (PNP)Rh fragment readily inserted into zinc–carbon bonds to form isolable molecules with covalent rhodium–zinc bonds.
Pillar[n]arene-based supramolecular organic frameworks with high hydrocarbon storage and selectivity
Authors: Tan Li-Li , Zhu Youlong , Long Hai , Jin Yinghua , Zhang Wei , Yang Ying-Wei
Published: May 2017

The high hydrocarbon storage capacity and adsorption selectivity of two low-density, solution-processable pillar[n]arene-based SOFs have been investigated for the first time.
Novel magnesium borides and their superconductivity
Authors: Davari Esfahani M. Mahdi , Zhu Qiang , Dong Huafeng , Oganov Artem R. , Wang Shengnan , Rakitin Maksim S. , Zhou Xiang-Feng
Published: May 2017

With the motivation of searching for new superconductors in the Mg–B system, we performed ab initio evolutionary searches for all the stable compounds in this binary system in the pressure range of 0–200 GPa.
Theoretical investigation of energy gap bowing in CdSxSe1−x alloy quantum dots
Authors: Tatikondewar Laxman , Kshirsagar Anjali
Published: May 2017

To investigate energy gap bowing in homogeneously alloyed CdSxSe1−x quantum dots (QDs) and to understand whether it is different from bulk, we perform density functional theory based electronic structure calculations for spherical QDs of different compositions x (0 ≤ x ≤ 1) and of varying sizes (2.2 to 4.6 nm).
Reliable nanometre-range distance distributions from 5-pulse double electron electron resonance
Authors: Breitgoff Frauke D. , Polyhach Yevhen O. , Jeschke Gunnar
Published: May 2017

The partial excitation artefact in 5-pulse DEER data can be eliminated by experimental time shifting and signal processing.
The dynamics of the Hg + Br2 reaction: elucidation of the reaction mechanism for the Br exchange reaction
Authors: Jambrina P. G. , Menéndez M. , Aoiz F. J.
Published: May 2017

The mechanism of the Hg + Br2 abstraction reaction reveals a richer and more complex dynamics that that could be expected.