bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-Awareness After Brain Injury: Relation with Emotion Recognition and Effects of Treatment
Authors: Lamberts K.F. , Fasotti L. , Boelen D.H.E. , Spikman J.M.
Published: November 2016

Self-awareness is often impaired after acquired brain injury (ABI) and this hampers rehabilitation, in general: unrealistic reports by patients about their functioning and poor motivation and compliance with treatment. We evaluated a self-awareness treatment that was part of a treatment protocol on executive dysfunction (Spikman, Boelen, Lamberts, Brouwer, & Fasotti, 2010). A total of 63 patients were included, aged 17–70, suffering non-progressive ABI, and minimum time post-onset of 3 months. Self-awareness was measured by comparing the patient's Dysexecutive Questionnaire (Wilson, Alderman, Burgess, Emslie, & Evans, 1996) score with that of an independent other. As emotion recognition is associated with self-awareness and influences the effect of rehabilitation treatment, we assessed this function using the Facial Expressions of Emotion-Stimuli and Tests (Young, Perrett, Calder, Sprengelmeyer, & Ekman, 2002). Results showed that patients in the experimental treatment group (n= 29) had better self-awareness after training than control patients (n= 34). Moreover, our results confirmed that the level of self-awareness before treatment was related to emotion recognition. Hence, self-awareness can improve after neuropsychological treatment fostering self-monitoring. Since neuropsychological treatment involves social learning, impairments in social cognition should be taken into account before starting and during treatment.
Using hypothetical product configurators to measure consumer preferences for nanoparticle size and concentration in sunscreens
Authors: Barnard Amanda S. , Louviere Jordan J. , Wei Edward , Zadorin Leon
Published: November 2016

Although nanoparticles have been shown to have clear technological advantages, their use in some consumer products remains controversial, particularly where these products come in direct contact with our bodies. There has been much discussion about using metal oxide nanoparticles in sunscreens, and numerous technology assessments aimed at predicting the type, size and concentration of nanoparticles and surface treatments that will be best for consumers. Yet, the optimal configuration is ultimately the one that people actually want and are willing to pay for, but until now consumer preferences have not been included in model predictions. We describe and discuss a proof of concept study in which we design and implement a hypothetical sunscreen product configurator to predict how people tradeoff sun protection factor (SPF), product transparency and potential toxicity from reactive oxygen species (ROS) in configuring their most preferred sunscreen. We also show that preferred nanoparticle sizes and concentrations vary across demographic groups. Our results suggest that while consumers choose to reduce or eliminate potential toxicity when possible, they do not automatically sacrifice high SPF and product transparency to avoid the possibility of toxicity from ROS. We discuss some advantages of using product configurators to study potential product designs and suggest some future research possibilities.
SOME NORMALITY CRITERIA AND A COUNTEREXAMPLE TO THE CONVERSE OF BLOCH’S PRINCIPLE
Authors: CHARAK KULDEEP SINGH , SHARMA SHITTAL
Published: November 2016

In this paper, we prove some value distribution results which lead to normality criteria for a family of meromorphic functions involving the sharing of a holomorphic function by more general differential polynomials generated by members of the family, and improve some recent results. In particular, the main result of this paper leads to a counterexample to the converse of Bloch’s principle.
Determinants of microstructural, dimensional and bone mineral changes postpartum in Swedish women
Authors: Brembeck Petra , Winkvist Anna , Ohlsson Claes , Lorentzon Mattias , Augustin Hanna
Published: November 2016

During lactation, areal (a) and volumetric (v) bone mineral density (BMD) are known to temporarily decrease. Factors that affect skeletal changes postpartum are not fully elucidated. The aim was to study determinants of the previously observed changes in aBMD at lumbar spine, and cortical vBMD, microstructure and dimensions at ultra-distal tibia postpartum. Women (25–40 years) were studied longitudinally at 2 weeks (baseline) and 4 months (n81), 12 months (n79) and 18 months (n58) postpartum. At each visit, blood samples were collected, body weight and height were measured and information about lactation habits, oestrogen contraceptives and physical activity was obtained. Ca intake was measured using 4-d food diaries at 4 months postpartum. Serum 25-hydroxyvitamin D (25OHD) was analysed by liquid chromatography-tandem MS. Skeletal changes were assessed with dual-energy X-ray absorptiometry and high-resolution peripheral quantitative computed tomography. Mean baseline BMI was 24·8 (sd3·1) kg/m2. Median (quartiles 1–3) duration of total lactation was 8·1 (6·8–10·4) months. Longer duration of full lactation was associated with larger decreases of lumbar spine aBMD and tibia vBMD and microstructure. Higher baseline body weight was associated with smaller decreases in tibia vBMD and microstructure. Higher Ca intake was associated with smaller decreases in tibia cortical vBMD and thickness. Higher baseline 25OHD was only associated with larger decreases in lumbar spine aBMD. In conclusion, lactation and body weight were the main determinants of skeletal changes during the first 18 months postpartum. Ca intake and serum concentrations of 25OHD appear to have different associations with cortical and trabecular bone.
Long-term spatio-temporal dynamics of the mosquito Aedes aegypti in temperate Argentina
Authors: Fischer S. , De Majo M.S. , Quiroga L. , Paez M. , Schweigmann N.
Published: November 2016

Buenos Aires city is located near the southern limit of the distribution of Aedes aegypti (Diptera: Culicidae). This study aimed to assess long-term variations in the abundance of Ae. aegypti in Buenos Aires in relation to changes in climatic conditions. Ae. aegypti weekly oviposition activity was analyzed and compared through nine warm seasons from 1998 to 2014, with 200 ovitraps placed across the whole extension of the city. The temporal and spatial dynamics of abundances were compared among seasons, and their relation with climatic variables were analyzed. Results showed a trend to higher peak abundances, a higher number of infested sites, and longer duration of the oviposition season through subsequent years, consistent with a long-term colonization process. In contrast, thermal favorability and rainfall pattern did not show a consistent trend of changes. The long-term increase in abundance, and the recently documented expansion of Ae. aegypti to colder areas of Buenos Aires province suggest that local populations might be adapting to lower temperature conditions. The steadily increasing abundances may have implications on the risk of dengue transmission.
The Epistolary Brush: Letter Writing and Power in Chosŏn Korea
Authors: Cho Hwisang
Published: November 2016

This article explores how new modes of writing and reading that developed in epistolary culture brought about intellectual, social, and political changes in Chosŏn society. From the sixteenth century onwards, the diverse uses of letters transformed the lifestyle and the mode of political participation of Confucian intellectuals. Letters became the main reading materials for neo-Confucian studies and self-cultivation as well as a medium for political action, especially for rural scholars, who innovated various epistolary genres to raise their political voices. New epistolary practices facilitated their collective activism, the spread of radical opinions, and the mobilization of new political groups. Toward the end of the dynasty, even nonelites emulated these practices for their activism. In this period, “spiral letters” developed in both vernacular Korean and literary Chinese letters. These new letter forms, used by both male elites and women, reflected and subverted the existing gender dynamics and power relations associated with the norms of reading and writing. The rise and fall of spiral letters demonstrate the mutual influence between the written culture and sociopolitical changes. The versatility and resourcefulness of epistolary practices characterized Chosŏn letter writers' fashionable choice of a radical lifestyle, which geared their social life to yield actual political power.
Markets and Medicine: Adam Smith and John Gregory
Authors: Downie Robin
Published: November 2016

It is generally assumed that transactions in a free market are based on self-interest. It is equally assumed that transactions between doctor and patients are aimed at the interests of the patient and in that sense are benevolent, fiduciary or based on trust. Influential statements of these positions derive from Adam Smith and from Smith's neighbour and contemporary John Gregory. Examining the views of Smith and Gregory but moving the issues into a contemporary context this paper will argue that the opposition of self-interest and benevolence is misleading and that in the modern world medicine and the market have a similar ethical framework.
Understanding second language fluency behavior: The effects of individual differences in first language fluency, cross-linguistic differences, and proficiency over time
Authors: HUENSCH AMANDA , TRACY-VENTURA NICOLE
Published: November 2016

This study examined the extent to which first language (L1) fluency behavior, cross-linguistic differences, and proficiency can predict second language (L2) fluency behavior over time. English L1 Spanish (n= 24) and French (n= 25) majors completed a picture-based oral narrative in the L2 before and after 5 months residing abroad and later in the L1 after returning home. Data were coded for seven measures of speed, breakdown, and repair fluency. The results from multiple regressions indicated that L1 fluency behavior, cross-linguistic differences, and proficiency differentially contributed to explaining L2 fluency behavior prior to and during immersion. These findings suggest that when investigating L1–L2 fluency relationships considerations of mitigating factors such as cross-linguistic differences are necessary, and it is worthwhile to focus on how the contributions of these factors shift during development.
China's Looming Human Capital Crisis: Upper Secondary Educational Attainment Rates and the Middle-income Trap
Authors: Khor Niny , Pang Lihua , Liu Chengfang , Chang Fang , Mo Di , Loyalka Prashant , Rozelle Scott
Published: November 2016

Accumulation of human capital is indispensable to spur economic growth. If students fail to acquire needed skills, not only will they have a hard time finding high-wage employment in the future but the development of the economies in which they work may also stagnate owing to a shortage of human capital. The overall goal of this study is to try to understand if China is ready in terms of the education of its labour force to progress from middle-income to high-income country status. To achieve this goal, we seek to understand the share of the labour force that has attained at least some upper secondary schooling (upper secondary attainment) and to benchmark these educational attainment rates against the rates of the labour forces in other countries (e.g. high-income/OECD countries; a subset of G20 middle-income/BRICS countries). Using the sixth population census data, we are able to show that China's human capital is shockingly poor. In 2010, only 24 per cent of China's entire labour force (individuals aged 25–64) had ever attended upper secondary school. This rate is less than one-third of the average upper secondary attainment rate in OECD countries. China's overall upper secondary attainment rate and the attainment rate of its youngest workers (aged 25–34) is also the lowest of all the BRICS countries (with the exception of India for which data were not available). Our analysis also demonstrates that the statistics on upper secondary education reported by the Ministry of Education (MoE) are overestimated. In the paper, we document when MoE and census-based statistics diverge, and raise three possible policy-based reasons why officials may have begun to have an incentive to misreport in the mid-2000s.
Adaptation and Acceptance: Moses Ḥayim Luzzatto's Sojourn in Amsterdam among Portuguese Jews
Authors: Sclar David
Published: November 2016

Although scholars have written extensively about Moses Ḥayim Luzzatto and his literary oeuvre, there has been virtually no work on his stay in Amsterdam (1735–43). The controversy over his supposed Sabbatianism, which engulfed much of the European rabbinate and led to his self-imposed exile from Padua, did not rage overtly in the Dutch Republic, and historians have generally regarded these years as nothing more than a quiet period for Luzzatto and of little consequence to him personally.

Using previously unpublished archival material, this article demonstrates that Luzzatto was highly regarded in Amsterdam's generally insular Portuguese community. He received charity and a regular stipend to study in the Ets Haim Yeshiva, forged relationships with both rabbinic and lay leaders, and arguably influenced the community's religious outlook. However, a comparison of the manuscript and print versions ofMesillat yesharim, his famous Musar treatise composed and published in the city, reveals the limitations under which Luzzatto lived. Research into Luzzatto's time in Amsterdam shows the man's enduring self-assurance and relentless critique of his critics, as well as the Portuguese rabbinate's broadening horizons.
The effect of giving respondents time to think in a choice experiment: a conditional cash transfer programme in South Africa
Authors: Tilley Elizabeth , Logar Ivana , Günther Isabel
Published: November 2016

We conducted a choice experiment (CE) to estimate willingness to accept (WTA) values for a planned conditional cash transfer (CCT) programme designed to increase toilet use in South Africa. The payment is made conditional on using a toilet and bringing urine to a central collection point. In a split-sample approach, a segment of respondents were given time to think (TTT) (24 hours) about their responses, while the remaining respondents had to answer immediately. We found significant differences in the choice behaviour between the subsamples. To validate the stated preferences with actual behaviour, a CCT programme was implemented afterwards. The stated WTA estimates were far below those revealed by actual behaviour for both subsamples. Contrary to our expectations, the TTT group had underestimated their actual WTA values by an even larger margin. The preferences for various attributes were nevertheless useful in informing the design of the real intervention.
The Effects of Menstrual Cycle Phase on Processing of Emotional	Images
Authors: Mačiukaitė Laura , Jarutytė Lina , Rukšėnas Osvaldas
Published: November 2016

Abstract. The ovarian hormone levels can affect subjective ratings and modulate late positive potential (LPP) amplitudes evoked by images of varying appeal. The present study examines how different progesterone levels influence the valence, arousal ratings and mean LPP amplitudes evoked by pleasant, neutral, and unpleasant images. Twenty-three healthy females were grouped by menstrual cycle days (estradiol and progesterone levels): 10 were included in the follicular phase group and 13 were included in the luteal phase group. Each female rated the affective images in terms of valence and arousal while event-related potentials (ERPs) were measured. The valence ratings of pleasant images were higher in follicular phase group than in luteal, but the same effect was not seen in the arousal ratings. The arousal ratings to unpleasant images were higher than those to pleasant in luteal, but not in follicular phase group. However, the mean amplitude of the early LPP (450–700 ms) was significantly greater to pleasant than to neutral and unpleasant stimuli, but did not differ between follicular and luteal phase groups. The mean amplitude of the late LPP (700–950 ms) was significantly larger to pleasant and unpleasant compared to neutral images, but did not differ between menstrual cycle phase groups. Correlation analysis showed a significant negative relationship between progesterone levels and arousal ratings of pleasant and unpleasant images in luteal phase group. Arousal scores for unpleasant images negatively correlated with mean LPP amplitudes to unpleasant images at Pz site in the luteal phase group. The present study provides evidence that subjective ratings of affective images of different attractiveness could be influenced by female menstrual cycle phase, but mean amplitudes of LPP (450–950 ms) are not affected. However, results of correlational analysis suggest that valence, arousal ratings and mean LPP amplitudes are susceptible to the influence of hormone progesterone in luteal phase.
Evaluative and Psychophysiological Responses to Short Film Clips of Different Emotional Content
Authors: Aguado Luis , Fernández-Cahill María , Román Francisco J. , Blanco Iván , de Echegaray Javier
Published: November 2016

Abstract. The study presents self-report and psychophysiological data obtained in response to short film clips representing scenes related to different emotions. This was done in order to obtain evidence on the structure of positive and negative affective states following a combined dimensional/categorical approach to emotion and based on responses to stimuli that are more realistic than the static pictures usually employed in the study of emotion. Affective ratings and self-report measures showed a differential structure of the response to positive and negative films (Experiment 1). While all negative films were rated as low in valence and high in arousal, positive films were differentiated into arousing (happy and pleasure contents) and de-arousing (relax contents) categories. A more complex pattern emerged in Experiment 2, using two psychophysiological measures that are differentially sensitive to the main affective dimensions of valence and arousal, skin conductance response (SCR) and facial electromyography (fEMG). First, high arousal positive and negative films produced larger skin conductance responses. Second, fEMG measures showed differentiated response patterns within the positive and negative film categories. Within the positive category, happy and relaxing films had opposed effects, with happy films increasing and relax films decreasing activity over the zygomaticus muscle region. In the case of negative films, only those eliciting disgust produced a differentiated pattern of fEMG activity characterized by large corrugator responses and a modest increase of zygomatic responses. These results are discussed in relation to the adequacy of the dimensional and categorical approaches to emotion, the usefulness of combining subjective and psychophysiological measures, and the advantages of using realistic, dynamic stimuli for the study of emotion.
Burnout of the Mind – Burnout of the Body?
Authors: Traunmüller Claudia , Gaisbachgrabner Kerstin , Lackner Helmut Karl , Schwerdtfeger Andreas R.
Published: November 2016

Abstract. In the present paper we investigate whether patients with a clinical diagnosis of burnout show physiological signs of burden across multiple physiological systems referred to as allostatic load (AL). Measures of the sympathetic-adrenergic-medullary (SAM) axis and the hypothalamic-pituitary-adrenal (HPA) axis were assessed. We examined patients who had been diagnosed with burnout by their physicians (n = 32) and were also identified as burnout patients based on their score in the Maslach Burnout Inventory-General Survey (MBI-GS) and compared them with a nonclinical control group (n = 19) with regard to indicators of allostatic load (i.e., ambulatory ECG, nocturnal urinary catecholamines, salivary morning cortisol secretion, blood pressure, and waist-to-hip ratio [WHR]). Contrary to expectations, a higher AL index suggesting elevated load in several of the parameters of the HPA and SAM axes was found in the control group but not in the burnout group. The control group showed higher norepinephrine values, higher blood pressure, higher WHR, higher sympathovagal balance, and lower percentage of cortisol increase within the first hour after awakening as compared to the patient group. Burnout was not associated with AL. Results seem to indicate a discrepancy between self-reported burnout symptoms and psychobiological load.
A Name Directory for the Ocean Floor
Authors: Stagpoole Vaughan , Schenke Hans , Ohara Yasuhiko
Published: November 2016

New Web resources enable scientists to standardize the naming of seamounts, trenches, and other undersea features, reducing ambiguity in identification and communication.
VCAM1 acts in parallel with CD69 and is required for the initiation of oligodendrocyte myelination
Authors: Miyamoto Yuki , Torii Tomohiro , Tanoue Akito , Yamauchi Junji
Published: November 2016

Oligodendrocytes differentiate to wrap their plasma membranes around axons, forming the myelin sheath. A neuronal cue is one of the regulator elements controlling this process. Here, we demonstrate that VCAM1, which plays a key role throughout the immune system, is also expressed in oligodendrocytes, where it regulates the initiation of myelination. VCAM1 knockout mice exhibit reduced myelin thickness. Decreased myelin thickness is also observed in mutant mice of α4 integrin, which is a neuronal VCAM1 ligand. Furthermore, CD69 is identified as one of the transcripts downregulated when VCAM1 is knocked down in oligodendrocytes. Knockdown of CD69 in mice indicates its role in myelination. Therefore, VCAM1 contributes not only to the initiation of myelination but also to its regulation through controlling the abundance of CD69, demonstrating that an intercellular molecule whose primary role is in the immune system can also play an unexpected role in the CNS.
Eradication of Pseudomonas aeruginosa biofilms and persister cells using an electrochemical scaffold and enhanced antibiotic susceptibility
Authors: Sultana Sujala T , Call Douglas R , Beyenal Haluk
Published: November 2016

Biofilms in chronic wounds are known to contain a persister subpopulation that exhibits enhanced multidrug tolerance and can quickly rebound after therapeutic treatment. The presence of these “persister cells” is partly responsible for the failure of antibiotic therapies and incomplete elimination of biofilms. Electrochemical methods combined with antibiotics have been suggested as an effective alternative for biofilm and persister cell elimination, yet the mechanism of action for improved antibiotic efficacy remains unclear. In this work, an electrochemical scaffold (e-scaffold) that electrochemically generates a constant concentration of H2O2was investigated as a means of enhancing tobramycin susceptibility in pre-grownPseudomonas aeruginosaPAO1 biofilms and attacking persister cells. Results showed that the e-scaffold enhanced tobramycin susceptibility inP. aeruginosaPAO1 biofilms, which reached a maximum susceptibility at 40 µg/ml tobramycin, with complete elimination (7.8-log reduction vs control biofilm cells,P ≤ 0.001). Moreover, the e-scaffold eradicated persister cells in biofilms, leaving no viable cells (5-log reduction vs control persister cells,P ≤ 0.001). It was observed that the e-scaffold induced the intracellular formation of hydroxyl free radicals and improved membrane permeability in e-scaffold treated biofilm cells, which possibly enhanced antibiotic susceptibility and eradicated persister cells. These results demonstrate a promising advantage of the e-scaffold in the treatment of persistent biofilm infections.
Logic models to predict continuous outputs based on binary inputs with an application to personalized cancer therapy
Authors: Knijnenburg Theo A. , Klau Gunnar W. , Iorio Francesco , Garnett Mathew J. , McDermott Ultan , Shmulevich Ilya , Wessels Lodewyk F. A.
Published: November 2016

Mining large datasets using machine learning approaches often leads to models that are hard to interpret and not amenable to the generation of hypotheses that can be experimentally tested. We present ‘Logic Optimization for Binary Input to Continuous Output’ (LOBICO), a computational approach that infers small and easily interpretable logic models of binary input features that explain a continuous output variable. Applying LOBICO to a large cancer cell line panel, we find that logic combinations of multiple mutations are more predictive of drug response than single gene predictors. Importantly, we show that the use of the continuous information leads to robust and more accurate logic models. LOBICO implements the ability to uncover logic models around predefined operating points in terms of sensitivity and specificity. As such, it represents an important step towards practical application of interpretable logic models.
DDIT4 regulates mesenchymal stem cell fate by mediating between HIF1α and mTOR signalling
Authors: Gharibi Borzo , Ghuman Mandeep , Hughes Francis J.
Published: November 2016

Stem cell fate decisions to remain quiescent, self-renew or differentiate are largely governed by the interplay between extracellular signals from the niche and the cell intrinsic signal cascades and transcriptional programs. Here we demonstrate that DNA Damage Inducible Transcript 4 (DDIT4) acts as a link between HIF1α and mTOR signalling and regulation of adult stem cell fate. Global gene expression analysis of mesenchymal stem cells (MSC) derived from single clones and live RNA cell sorting showed a direct correlation between DDIT4 and differentiation potentials of MSC. Loss and gain of function analysis demonstrated that DDIT4 activity is directly linked to regulation of mTOR signalling, expression of pluripotency genes and differentiation. Further we demonstrated that DDIT4 exert these effects down-stream to HIF1α. Our findings provide an insight in regulation of adult stem cells homeostasis by two major pathways with opposing functions to coordinate between states of self-renewal and differentiation.
BGRMI: A method for inferring gene regulatory networks from time-course gene expression data and its application in breast cancer research
Authors: Iglesias-Martinez Luis F. , Kolch Walter , Santra Tapesh
Published: November 2016

Reconstructing gene regulatory networks (GRNs) from gene expression data is a challenging problem. Existing GRN reconstruction algorithms can be broadly divided into model-free and model–based methods. Typically, model-free methods have high accuracy but are computation intensive whereas model-based methods are fast but less accurate. We propose Bayesian Gene Regulation Model Inference (BGRMI), a model-based method for inferring GRNs from time-course gene expression data. BGRMI uses a Bayesian framework to calculate the probability of different models of GRNs and a heuristic search strategy to scan the model space efficiently. Using benchmark datasets, we show that BGRMI has higher/comparable accuracy at a fraction of the computational cost of competing algorithms. Additionally, it can incorporate prior knowledge of potential gene regulation mechanisms and TF hetero-dimerization processes in the GRN reconstruction process. We incorporated existing ChIP-seq data and known protein interactions between TFs in BGRMI as sources of prior knowledge to reconstruct transcription regulatory networks of proliferating and differentiating breast cancer (BC) cells from time-course gene expression data. The reconstructed networks revealed key driver genes of proliferation and differentiation in BC cells. Some of these genes were not previously studied in the context of BC, but may have clinical relevance in BC treatment.
An amino acid-based oral rehydration solution (AA-ORS) enhanced intestinal epithelial proliferation in mice exposed to radiation
Authors: Yin Liangjie , Gupta Reshu , Vaught Lauren , Grosche Astrid , Okunieff Paul , Vidyasagar Sadasivan
Published: November 2016

Destruction of clonogenic cells in the crypt following irradiation are thought to cause altered gastrointestinal function. Previously, we found that an amino acid-based oral rehydration solution (AA-ORS) improved gastrointestinal function in irradiated mice. However, the exact mechanisms were unknown. Electrophysiology, immunohistochemistry, qPCR, and Western blot analysis were used to determine that AA-ORS increased proliferation, maturation, and differentiation and improved electrolyte and nutrient absorption in irradiated mice. A single-hit, multi-target crypt survival curve showed a significant increase in crypt progenitors in irradiated mice treated with AA-ORS for six days (8.8 ± 0.4) compared to the saline-treated group (6.1 ± 0.3; P < 0.001) without a change in D0 (4.8 ± 0.1 Gy). The Dq values increased from 8.8 ± 0.4 Gy to 10.5 ± 0.5 Gy with AA-ORS treatment (P < 0.01), indicating an increased radiation tolerance of 1.7 Gy. We also found that AA-ORS treatment (1) increased Lgr5+, without altering Bmi1 positive cells; (2) increased levels of proliferation markers (Ki-67, p-Erk, p-Akt and PCNA); (3) decreased apoptosis markers, such as cleaved caspase-3 and Bcl-2; and (4) increased expression and protein levels of NHE3 and SGLT1 in the brush border membrane. This study shows that AA-ORS increased villus height and improved electrolyte and nutrient absorption.
mTORC1 is Required for Brown Adipose Tissue Recruitment and Metabolic Adaptation to Cold
Authors: Labbé Sébastien M. , Mouchiroud Mathilde , Caron Alexandre , Secco Blandine , Freinkman Elizaveta , Lamoureux Guillaume , Gélinas Yves , Lecomte Roger , Bossé Yohan , Chimin Patricia , Festuccia William T. , Richard Denis , Laplante Mathieu
Published: November 2016

In response to cold, brown adipose tissue (BAT) increases its metabolic rate and expands its mass to produce heat required for survival, a process known as BAT recruitment. The mechanistic target of rapamycin complex 1 (mTORC1) controls metabolism, cell growth and proliferation, but its role in regulating BAT recruitment in response to chronic cold stimulation is unknown. Here, we show that cold activates mTORC1 in BAT, an effect that depends on the sympathetic nervous system. Adipocyte-specific mTORC1 loss in mice completely blocks cold-induced BAT expansion and severely impairs mitochondrial biogenesis. Accordingly, mTORC1 loss reduces oxygen consumption and causes a severe defect in BAT oxidative metabolism upon cold exposure. Using in vivo metabolic imaging, metabolomics and transcriptomics, we show that mTORC1 deletion impairs glucose and lipid oxidation, an effect linked to a defect in tricarboxylic acid (TCA) cycle activity. These analyses also reveal a severe defect in nucleotide synthesis in the absence of mTORC1. Overall, these findings demonstrate an essential role for mTORC1 in the regulation of BAT recruitment and metabolism in response to cold.
The N-terminal loop of IRAK-4 death domain regulates ordered assembly of the Myddosome signalling scaffold
Authors: Dossang Anthony C. G. , Motshwene Precious G. , Yang Yang , Symmons Martyn F. , Bryant Clare E. , Borman Satty , George Julie , Weber Alexander N. R. , Gay Nicholas J.
Published: November 2016

Activation of Toll-like receptors induces dimerization and the recruitment of the death domain (DD) adaptor protein MyD88 into an oligomeric post receptor complex termed the Myddosome. The Myddosome is a hub for inflammatory and oncogenic signaling and has a hierarchical arrangement with 6–8 MyD88 molecules assembling with exactly 4 of IRAK-4 and 4 of IRAK-2. Here we show that a conserved motif in IRAK-4 (Ser8-X-X-X-Arg12) is autophosphorylated and that the phosphorylated DD is unable to form Myddosomes. Furthermore a mutant DD with the phospho-mimetic residue Asp at this position is impaired in both signalling and Myddosome assembly. IRAK-4 Arg12 is also essential for Myddosome assembly and signalling and we propose that phosphorylated Ser8 induces the N-terminal loop to fold into an α-helix. This conformer is stabilised by an electrostatic interaction between phospho-Ser8 and Arg12 and would destabilise a critical interface between IRAK-4 and MyD88. Interestingly IRAK-2 does not conserve this motif and has an alternative interface in the Myddosome that requires Arg67, a residue conserved in paralogues, IRAK-1 and 3(M).
Experienced migratory songbirds do not display goal-ward orientation after release following a cross-continental displacement: an automated telemetry study
Authors: Kishkinev Dmitry , Heyers Dominik , Woodworth Bradley K. , Mitchell Greg W. , Hobson Keith A. , Norris D. Ryan
Published: November 2016

The ability to navigate implies that animals have the capability to compensate for geographical displacement and return to their initial goal or target. Although some species are capable of adjusting their direction after displacement, the environmental cues used to achieve this remain elusive. Two possible cues are geomagnetic parameters (magnetic map hypothesis) or atmospheric odour-forming gradients (olfactory map hypothesis). In this study, we examined both of these hypotheses by surgically deactivating either the magnetic or olfactory sensory systems in experienced white-throated sparrows (Zonotrichia albicollis) captured in southern Ontario, Canada, during spring migration. Treated, sham-treated, and intact birds were then displaced 2,200 km west to Saskatchewan, Canada. Tracking their initial post-displacement migration using an array of automated VHF receiving towers, we found no evidence in any of the groups for compensatory directional response towards their expected breeding grounds. Our results suggest that white-throated sparrows may fall back to a simple constant-vector orientation strategy instead of performing true navigation after they have been geographically displaced to an unfamiliar area during spring migration. Such a basic strategy may be more common than currently thought in experienced migratory birds and its occurrence could be determined by habitat preferences or range size.
Multiple crosstalk between TOR and the cell integrity MAPK signaling pathway in fission yeast
Authors: Madrid Marisa , Vázquez-Marín Beatriz , Franco Alejandro , Soto Teresa , Vicente-Soler Jero , Gacto Mariano , Cansado José
Published: November 2016

In eukaryotic cells, the highly conserved Target of Rapamycin (TOR) and the Mitogen Activated Protein Kinase (MAPK) signaling pathways elicit adaptive responses to extra- and intracellular conditions by regulating essential cellular functions. However, the nature of the functional relationships between both pathways is not fully understood. In the fission yeast Schizosaccharomyces pombe the cell integrity MAPK pathway (CIP) regulates morphogenesis, cell wall structure and ionic homeostasis. We show that the Rab GTPase Ryh1, a TORC2 complex activator, cross-activates the CIP and its core member, the MAPK Pmk1, by two distinct mechanisms. The first one involves TORC2 and its downstream effector, Akt ortholog Gad8, which together with TORC1 target Psk1 increase protein levels of the PKC ortholog Pck2 during cell wall stress or glucose starvation. Also, Ryh1 activates Pmk1 in a TORC2-independent fashion by prompting plasma membrane trafficking and stabilization of upstream activators of the MAPK cascade, including PDK ortholog Ksg1 or Rho1 GEF Rgf1. Besides, stress-activated Pmk1 cross-inhibits Ryh1 signaling by decreasing the GTPase activation cycle, and this ensures cell growth during alterations in phosphoinositide metabolism. Our results reveal a highly intricate cross-regulatory relationship between both pathways that warrants adequate cell adaptation and survival in response to environmental changes.
Novel structure in sciaenid fish skulls indicates continuous production of the cephalic neuromast cupula
Authors: Pombo Maíra , Turra Alexander
Published: November 2016

The presence of a conspicuous and frequent but never-described structure in the skull cavities of sciaenid fish was noted during population studies in an urbanized bay. The ultrastructure closely resembles the cupula of neuromasts, an organ associated with the perception of the environment in teleost fish. The bodies were recorded detached in both preserved and freshly sampled individuals and without associated cilia. Prominent characteristics are acellularity, the elliptic-conic shape composed of stack-like protein lamellas, and a mesh-like appearance in cross section. These acellular lamellar cephalic bodies (ALCBs) were more abundant in larger individuals and showed temporal peaks of abundance independently of the fish size. The conic and lamellar features suggest that the deposition of protein layers follows fish growth, and the bimodality of the size of these structures in individuals indicates temporal peaks of production. These results indicate that these ALCBs are a consequence of the accretion of the cupula of neuromasts at a faster rate than they degrade. Given the novelty of this structure and the increasing records of diseases of marine organisms worldwide, an important question is whether these bodies occur subsequently to some environmental change and whether their accumulation in the skull cavities has consequences to fish health.
The measurement of lung volumes using body plethysmography and helium dilution methods in COPD patients: a correlation and diagnosis analysis
Authors: Tang Yongjiang , Zhang Mingke , Feng Yulin , Liang Binmiao
Published: November 2016

Chronic obstructive pulmonary disease (COPD) is a chronic airway disease characterized by persistent airflow limitation. Moreover, lung hyperinflation evaluated by lung volumes is also the key pathophysiologic process during COPD progression. Nevertheless, there is still no preferred method to evaluate lung volumes. For this study, we recruited 170 patients with stable COPD to assess lung volumes stratified by airflow limitation severity. Lung volumes including residual volume (RV) and total lung capacity (TLC) were determined by both body plethysmography and helium dilution methods. The discrepancies between these two methods were recorded as ΔRV%pred, ΔTLC%pred, and ΔRV/TLC. We found that ΔRV%pred, ΔTLC%pred, and ΔRV/TLC increased significantly with the severity of COPD. The differences of lung capacity between these two methods were negatively correlated with FEV1%pred, and diffusing capacity for carbon monoxide (DLCO%pred). Moreover, the receiver operating characteristic (ROC) for ΔTLC%pred to distinguish severe COPD from non-severe COPD had an area under curve (AUC) of 0.886. The differences of lung volume parameters measured by body plethysmography and helium dilution methods were associated with airflow limitation and can effectively differentiate COPD severity, which may be a supportive method to assess the lung function of stable COPD patients.
In Silico Exploration for Novel Type-I Inhibitors of Tie-2/TEK: The Performance of Different Selection Strategy in Selecting Virtual Screening Candidates
Authors: Pan Peichen , Sun Huiyong , Liu Hui , Li Dan , Zhou Wenfang , Kong Xiaotian , Li Youyong , Yu Huidong , Hou Tingjun
Published: November 2016

The receptor tyrosine kinase Tie-2 is involved in vessel remodeling and maturation, and has been regarded as a potential target for the treatment of various solid tumors. The absence of novel, potent and selective inhibitors severely hampers the understanding of the therapeutic potential of Tie-2. In the present work, we describe the discovery of novel type-I inhibitors of Tie-2 by structure-based virtual screening. Preliminary SAR was also performed based on one active compound, and several novel inhibitors with low micro-molar affinity were discovered. To directly compare the efficiency between different filtering strategies in selecting VS candidates, two methods were separately carried out to screen the same chemical library, and the selected VS candidates were then experimentally assessed by in vitro enzymatic assays. The results demonstrate that the hit rate is improved when stricter drug-likeness criteria and less number of molecules for clustering analysis are used, and meanwhile, the molecular diversity of the compounds still maintains. As a case study of TIE-2, the information presented in this work underscores the importance of selecting an appropriate selection strategy in VS campaign, and the novel inhibitors identified and the detailed binding modes of action provide a starting point for further hit-to-lead optimization process.
ENSO’s far reaching connection to Indian cold waves
Authors: Ratnam J. V. , Behera Swadhin K. , Annamalai H. , Ratna Satyaban B. , Rajeevan M. , Yamagata Toshio
Published: November 2016

During boreal winters, cold waves over India are primarily due to transport of cold air from higher latitudes. However, the processes associated with these cold waves are not yet clearly understood. Here by diagnosing a suite of datasets, we explore the mechanisms leading to the development and maintenance of these cold waves. Two types of cold waves are identified based on observed minimum surface temperature and statistical analysis. The first type (TYPE1), also the dominant one, depicts colder than normal temperatures covering most parts of the country while the second type (TYPE2) is more regional, with significant cold temperatures only noticeable over northwest India. Quite interestingly the first (second) type is associated with La Niña (El Niño) like conditions, suggesting that both phases of ENSO provide a favorable background for the occurrence of cold waves over India. During TYPE1 cold wave events, a low-level cyclonic anomaly generated over the Indian region as an atmospheric response to the equatorial convective anomalies is seen advecting cold temperatures into India and maintaining the cold waves. In TYPE2 cold waves, a cyclonic anomaly generated over west India anomalously brings cold winds to northwest India causing cold waves only in those parts.
The Reproductive Toxicity of CdSe/ZnS Quantum Dots on the in vivo Ovarian Function and in vitro Fertilization
Authors: Xu Gaixia , Lin Guimiao , Lin Suxia , Wu Na , Deng Yueyue , Feng Gang , Chen Qiang , Qu Junle , Chen Danni , Chen Siping , Niu Hanben , Mei Shujiang , Yong Ken-Tye , Wang Xiaomei
Published: November 2016

Despite the usefulness of quantum dots (QDs) in biomedicine and optoelectronics, their toxicity risks remain a major obstacle for clinical usages. Hence, we studied the reproductive toxicity of CdSe/ZnS QDs on two aspects, (i) in vivo ovarian functions and (ii) in vitro fertilization process. The body weight, estrous cycles, biodistribution of QDs, and oocyte maturation are evaluated on female mice treated with QDs. The mRNA level of the follicle-stimulating hormone receptor (FSHr) and luteinizing hormone receptor (LHr) in ovaries are assayed. Then, the matured cumulus-oocyte-complexes are harvested to co-culture with in vitro capacitated sperms, and the in vitro fertilization is performed. The result revealed that QDs are found in the ovaries, but no changes are detected on the behavior and estrous cycle on the female mice. The mRNA downregulations of FSHr and LHr are observed and the number of matured oocytes has shown a significant decrease when the QDs dosage was above 1.0 pmol/day. Additionally, we found the presence of QDs has reduced the in vitro fertilization success rate. This study highly suggests that the exposure of CdSe/ZnS QDs to female mice can cause adverse effects to the ovary functions and such QDs may have limited applications in clinical usage.
Fabrication of functional hollow microspheres constructed from MOF shells: Promising drug delivery systems with high loading capacity and targeted transport
Authors: Gao Xuechuan , Hai Xiao , Baigude Huricha , Guan Weihua , Liu Zhiliang
Published: November 2016

An advanced multifunctional, hollow metal-organic framework (MOF) drug delivery system with a high drug loading level and targeted delivery was designed and fabricated for the first time and applied to inhibit tumour cell growth. This hollow MOF targeting drug delivery system was prepared via a simple post-synthetic surface modification procedure, starting from hollow ZIF-8 successfully obtained for the first time via a mild phase transformation under solvothermal conditions. As a result, the hollow ZIF-8 exhibits a higher loading capacity for the model anticancer drug 5-fluorouracil (5-FU). Subsequently, 5-FU-loaded ZIF-8 was encapsulated into polymer layers (FA-CHI-5-FAM) with three components: a chitosan (CHI) backbone, the imaging agent 5-carboxyfluorescein (5-FAM), and the targeting reagent folic acid (FA). Thus, an advanced drug delivery system, ZIF-8/5-FU@FA-CHI-5-FAM, was fabricated. A cell imaging assay demonstrated that ZIF-8/5-FU@FA-CHI-5-FAM could target and be taken up by MGC-803 cells. Furthermore, the as-prepared ZIF-8/5-FU@FA-CHI-5-FAM exhibited stronger cell growth inhibitory effects on MGC-803 cells because of the release of 5-FU, as confirmed by a cell viability assay. In addition, a drug release experiment in vitro indicated that ZIF-8/5-FU@FA-CHI-5-FAM exhibited high loading capacity (51%) and a sustained drug release behaviour. Therefore, ZIF-8/5-FU@FA-CHI-5-FAM could provide targeted drug transportation, imaging tracking and localized sustained release.
Possible generation of heat from nuclear fusion in Earth’s inner core
Authors: Fukuhara Mikio
Published: November 2016

The cause and source of the heat released from Earth’s interior have not yet been determined. Some research groups have proposed that the heat is supplied by radioactive decay or by a nuclear georeactor. Here we postulate that the generation of heat is the result of three-body nuclear fusion of deuterons confined in hexagonal FeDx core-centre crystals; the reaction rate is enhanced by the combined attraction effects of high-pressure (~364 GPa) and high-temperature (~5700 K) and by the physical catalysis of neutral pions: 2D + 2D + 2D → 21H + 4He + 2 "Equation missing" + 20.85 MeV. The possible heat generation rate can be calculated as 8.12 × 1012 J/m3, based on the assumption that Earth’s primitive heat supply has already been exhausted. The H and He atoms produced and the anti-neutrino "Equation missing" are incorporated as Fe-H based alloys in the H-rich portion of inner core, are released from Earth’s interior to the universe, and pass through Earth, respectively.
Evaluation of the efficacy of Myco/F lytic system, MGIT960 system and Lowenstein-Jensen medium for recovery of Mycobacterium tuberculosis from sterile body fluids
Authors: Wang Guirong , Yang Xinting , Zhu Junping , Dong Weijie , Huang Mailing , Jiang Guanglu , Zhao Liping , Qin Sibing , Chen Xiaoyou , Huang Hairong
Published: November 2016

The diagnosis of extrapulmonary tuberculosis (EPTB) is challenging due to non-specific symptoms, invasive approach for specimen collection and most importantly, the paucibacillary status. The objective of this assay was to evaluate the efficacy of Myco/F lytic system, BACTEC Mycobacteria Growth Indicator Tube (MGIT) 960 system and Lowenstein-Jensen (L-J) medium for recovery of bacilli from sterile body fluids. 214 specimens (114 pleural fluid and 100 pus) from clinically diagnosed EPTB patients were collected and subjected to Ziehl-Neelsen (ZN) smear microscopy, L-J culture, MGIT 960 culture and Myco/F lytic culture.103 out of the 214 sterile body fluid samples yielded positive culture outcomes by any of the three methods. Among all the culture positive specimens, the recovery rate was 86.41% for Myco/F lytic, 75.73% for MGIT 960, and 42.72% for L-J medium. The mean time to positivity (TTP) was 27.06 ± 8.03 days for Myco/F lytic, 22.20 ± 7.84 days for MGIT960 and 42 ± 8.84 days for L-J medium. The rates of contamination were 6.54%, 3.74% and 2.80% for Myco/F lytic, MGIT960 and L-J medium respectively. Both Myco/F lytic and MGIT960 system were superior to L-J medium for recovery of bacilli from sterile body fluids. Myco/F lytic system was more favorable than MGIT960 regarding recovery rate and cost-effectiveness, thus can be considered as a promising alternative to MGIT960 system for diagnosing EPTB.