bluuebunny/crossref_metadata_2025 huggingface dataset:
Local anaesthesia and conscious sedation for cochlear implantation: experience with 20 patients
Authors: Pateron B , Bakhos D , LeLouarn A , Bordure P , Bozorg Grayeli A , Godey B , Lescanne E
Published: December 2015

Objective:

Cochlear implantation is mostly performed under general anaesthesia. This study aimed to evaluate cochlear implantation performed under local anaesthesia and sedation.

Method:

Twenty patients had a cochlear implant fitted under combined local anaesthesia (local anaesthesia group) and 41 patients had one fitted under general anaesthesia (general anaesthesia group) for bilateral profound hearing loss, from 2011 to 2014. Surgical duration, period of post-operative hospitalisation and early post-operative symptoms were compared. In the local anaesthesia group, operative symptoms reported during the surgery and by questionnaire were analysed.

Results:

Mean surgical duration was significantly shorter in the local anaesthesia group: 87 versus 122 minutes (p< 0.001). No significant difference was observed between the local anaesthesia and general anaesthesia groups regarding mean post-operative hospitalisation and early post-operative symptoms. Under local anaesthesia, patients had no particular symptoms in 60 per cent of cases. The remaining patients in this group experienced vertigo (10 per cent), pain (20 per cent) and pain-related movement (10 per cent) during the intervention. These symptoms can be controlled with symptomatic treatment.

Conclusion:

Combined local anaesthesia for cochlear implantation is a good alternative to general anaesthesia for co-operating patients.
Depression as a systemic syndrome: mapping the feedback loops of major depressive disorder
Authors: Wittenborn A. K. , Rahmandad H. , Rick J. , Hosseinichimeh N.
Published: December 2015

Background

Depression is a complex public health problem with considerable variation in treatment response. The systemic complexity of depression, or the feedback processes among diverse drivers of the disorder, contribute to the persistence of depression. This paper extends prior attempts to understand the complex causal feedback mechanisms that underlie depression by presenting the first broad boundary causal loop diagram of depression dynamics.

Method

We applied qualitative system dynamics methods to map the broad feedback mechanisms of depression. We used a structured approach to identify candidate causal mechanisms of depression in the literature. We assessed the strength of empirical support for each mechanism and prioritized those with support from validation studies. Through an iterative process, we synthesized the empirical literature and created a conceptual model of major depressive disorder.

Results

The literature review and synthesis resulted in the development of the first causal loop diagram of reinforcing feedback processes of depression. It proposes candidate drivers of illness, or inertial factors, and their temporal functioning, as well as the interactions among drivers of depression. The final causal loop diagram defines 13 key reinforcing feedback loops that involve nine candidate drivers of depression.

Conclusions

Future research is needed to expand upon this initial model of depression dynamics. Quantitative extensions may result in a better understanding of the systemic syndrome of depression and contribute to personalized methods of evaluation, prevention and intervention.
Disruption of effective connectivity from the dorsolateral prefrontal cortex to the orbitofrontal cortex by negative emotional distraction in obsessive–compulsive disorder
Authors: Han H. J. , Jung W. H. , Yun J.-Y. , Park J. W. , Cho K. K. , Hur J.-W. , Shin N. Y. , Lee T. Y. , Kwon J. S.
Published: December 2015

Background

Obsessive–compulsive disorder (OCD) has been associated with abnormal cognitive and emotional functions and these dysfunctions may be dependent on the disruption of dynamic interactions within neuronal circuits associated with emotion regulation. Although several studies have shown the aberrant cognitive–affective processing in OCD patients, little is known about how to characterize effective connectivity of the disrupted neural interactions. In the present study, we applied effective connectivity analysis using dynamic causal modeling to explore the disturbed neural interactions in OCD patients.

Method

A total of 20 patients and 21 matched healthy controls performed a delayed-response working memory task under emotional or non-emotional distraction while undergoing functional magnetic resonance imaging.

Results

During the delay interval under negative emotional distraction, both groups showed similar patterns of activations in the amygdala. However, under negative emotional distraction, the dorsolateral prefrontal cortex (DLPFC) and the orbitofrontal cortex (OFC) exhibited significant differences between groups. Bayesian model averaging indicated that the connection from the DLPFC to the OFC was negatively modulated by negative emotional distraction in patients, when compared with healthy controls (p< 0.05, Bonferroni-corrected).

Conclusions

Exaggerated recruitment of the DLPFC may induce the reduction of top-down prefrontal control input over the OFC, leading to abnormal cortico-cortical interaction. This disrupted cortico-cortical interaction under negative emotional distraction may be responsible for dysfunctions of cognitive and emotional processing in OCD patients and may be a component of the pathophysiology associated with OCD.
The association between childhood relocations and subsequent risk of suicide attempt, psychiatric problems, and low academic achievement
Authors: Bramson L. M. , Rickert M. E. , Class Q. A. , Sariaslan A. , Almqvist C. , Larsson H. , Lichtenstein P. , D'Onofrio B. M.
Published: December 2015

Background

Given the frequency with which families change residences, the effects of childhood relocations have gained increasing research attention. Many researchers have demonstrated that childhood relocations are associated with a variety of adverse outcomes. However, drawing strong causal claims remains problematic due to uncontrolled confounding factors.

Method

We utilized longitudinal, population-based Swedish registers to generate a nationally representative sample of offspring born 1983–1997 (n= 1 510 463). Using Cox regression and logistic regression, we examined the risk for numerous adverse outcomes after childhood relocation while controlling for measured covariates. To account for unmeasured genetic and environmental confounds, we also compared differentially exposed cousins and siblings.

Results

In the cohort baseline model, each annual relocation was associated with risk for the adverse outcomes, including suicide attempt [hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.19–1.20]. However, when accounting for offspring and parental covariates (HR 1.08, 95% CI 1.07–1.09), as well as genetic and environmental confounds shared by cousins (HR 1.07, 95% CI 1.05–1.09) and siblings (HR 1.00, 95% CI 0.97–1.04), the risk for suicide attempt attenuated. We found a commensurate pattern of results for severe mental illness, substance abuse, criminal convictions, and low academic achievement.

Conclusions

Previous research may have overemphasized the independent association between relocations and later adverse outcomes. The results suggest that the association between childhood relocations and suicide attempt, psychiatric problems, and low academic achievement is partially explained by genetic and environmental confounds correlated with relocations. This study demonstrates the importance of using family-based, quasi-experimental designs to test plausible alternate hypotheses when examining causality.
Speech rates converge in scripted turn-taking conversations
Authors: SCHULTZ BENJAMIN G. , O’BRIEN IRENA , PHILLIPS NATALIE , McFARLAND DAVID H. , TITONE DEBRA , PALMER CAROLINE
Published: December 2015

When speakers engage in conversation, acoustic features of their utterances sometimes converge. We examined how the speech rate of participants changed when a confederate spoke at fast or slow rates during readings of scripted dialogues. A beat-tracking algorithm extracted the periodic relations between stressed syllables (beats) from acoustic recordings. The mean interbeat interval (IBI) between successive stressed syllables was compared across speech rates. Participants’ IBIs were smaller in the fast condition than in the slow condition; the difference between participants’ and the confederate's IBIs decreased across utterances. Cross-correlational analyses demonstrated mutual influences between speakers, with greater impact of the confederate on participants’ beat rates than vice versa. Beat rates converged in scripted conversations, suggesting speakers mutually entrain to one another's beat.
Intergenerational inequity arguments and the implications for state-funded financial support of older people
Authors: HURLEY KAREN , BREHENY MARY , TUFFIN KEITH
Published: December 2015

As population demographics shift towards an older population structure in the Western world, concerns about the future costs of pensions are apparent in politics, media and everyday conversations. In New Zealand, the universal state-funded pension paid to all citizens over the age of 65 years is often considered to be unsustainable in the context of population ageing. To examine the arguments surrounding universal superannuation, rhetorical analysis was undertaken on two New Zealand newspaper articles that discussed the future cost of pensions, and the 233 public responses these articles generated. The cost of superannuation was used to emphasise the different characteristics of each generational cohort and the ways that this produced inequity across generations. Claims of intergenerational inequity generated antagonism and widened divisions between generational groups. Foregrounding generational inequity in the discussion of superannuation has profound implications for state-funded income support for older people which relies upon widespread public support. Intergenerational inequity ignores the significant inequity in health and social circumstances in retirement among older New Zealanders and overlooks the significant impact of universal superannuation on protecting older New Zealanders from poverty in later life.
ELLSBERG’S PARADOX AND THE VALUE OF CHANCES
Authors: Bradley Richard
Published: December 2015

What value should we put on our chances of obtaining a good? This paper argues that, contrary to the widely accepted theory of von Neumann and Morgenstern, the value of a chance of some good G may be a non-linear function of the value of G. In particular, chances may have diminishing marginal utility, a property that is termed chance uncertainty aversion. The hypothesis that agents are averse to uncertainy about chances explains a pattern of preferences often observed in the Ellsberg paradox. While these preferences have typically been taken to refute Bayesian decision theory, it is shown that chance risk aversion is perfectly compatible with it.
EXPLOITATION AND DISADVANTAGE
Authors: Ferguson Benjamin
Published: December 2015

According to some accounts of exploitation, most notably Ruth Sample’s (2003) degradation-based account and Robert Goodin’s (1987) vulnerability-based account, exploitation occurs when an advantaged party fails to constrain their advantage in light of another’s disadvantage, regardless of the cause of this disadvantage. Because the duty of constraint in these accounts does not depend on the cause of the disadvantage, the advantaged’s duty of constraint is what I call a ‘come-what-may’ duty. I show that come-what-may duties create moral hazards that can themselves be exploited by the disadvantaged parties. In such cases these accounts of exploitation are either self-frustrating or over-demanding.
Individual status quo modelling for a rural water service in Rwanda: application of a choice experiment
Authors: Uwera Claudine , Stage Jesper
Published: December 2015

In Rwanda, rural water supply is not uniformly distributed. Rural areas are characterized by differences in the distance to the nearest water point and in water quality for domestic water, by watering frequency and water availability for irrigation water, and by the price for both. A household's perception of further improvements in water supply will, therefore, depend heavily on the situation it currently faces. The authors used a choice experiment to model how the individual status quo (SQ) affects preferences. Accounting for individual SQ information improves model significance relative to simply using the generic SQ parameter in the model, and the willingness to pay increases. Not using this information leads to a downward bias – and, in some cases, statistical insignificance – in estimates of households’ valuation of health improvements linked to improved domestic water availability, as well as of increased watering frequency linked to the improved availability of irrigation water.
The indivisibility of the French republic as political theory and constitutional doctrine
Authors: Daly Eoin
Published: December 2015

Indivisibility of the French republic – sovereignty and French republicanism – universalism in French political thought – spatial and social dimensions of the indivisibility doctrine – indivisibility and identity-based classifications – Dilution of the indivisibility doctrine – a crisis of French universalism
Multilevel Constitutionalism and the Crisis of Democracy in Europe
Authors: Pernice Ingolf
Published: December 2015

Misconception of the EU is the reason for increasing scepticism – multilevel constitutionalism: conceptualising the EU as a matter of the citizens – critiques and the defence of multilevel constitutionalism – European treaties as a form of a new supranational social contract – embedded autonomy in a system of divided sovereignty – explaining and enhancing democratic legitimacy of the EU – the legitimising principles of additionality, of voluntariness and of open democracy – taking ownership of the EU and taking subsidiarity seriously – backing the European monetary policy by new competences for a common economic and fiscal policies – engaging in European policies as a way out of the crisis.
An Immigrant's Tale: The Mexican American Southwest 1850 to 1950
Authors: Gratton Brian , Merchant Emily Klancher
Published: December 2015

Recent scholarship on Mexican Americans in the United States, relying largely on qualitative evidence, sees racism and exploitation as the major explanatory factors in their history. Using representative samples of persons of Mexican origin, we argue that immigration is fundamental to their historical experience. A small, beleaguered community in 1850, the Mexican-origin population grew during the late nineteenth century due to greater security under US jurisdiction. However, immigration between 1900 and 1930 created a Southwest broadly identified with persons of Mexican origin. Economic development in Mexico, restriction of European immigration to the United States, and extreme cross-border wage differentials prompted extensive emigration. Despite low human capital, circular migration, and discrimination, immigrant Mexicans earned substantially higher wages than workers in Mexico or native-born Hispanics in the United States. They followed typical immigrant paths toward urban areas with high wages. Prior to 1930, their marked tendency to repatriate was not “constructed” or compelled by the state or employers, but fit a conventional immigrant strategy. During the Depression, many persons of Mexican origin migrated to Mexico; some were deported or coerced, but others followed this well-established repatriation strategy. The remaining Mexican-origin population, increasingly native born, enjoyed extraordinary socioeconomic gains in the 1940s; upward mobility, their family forms, and rising political activity resembled those of previous immigrant-origin communities. In the same decade, however, the Bracero Program prompted mass illegal immigration and mass deportation, a pattern replicated throughout the late twentieth century. These conditions repeatedly replenished ethnicity and reignited nativism, presenting a challenge not faced by any other immigrant group in US history.
Epigenome-Wide Association Study of Wellbeing
Authors: Baselmans Bart M. L. , van Dongen Jenny , Nivard Michel G. , Lin Bochao D. , Consortium BIOS , Zilhão Nuno R. , Boomsma Dorret I. , Bartels Meike
Published: December 2015

Wellbeing (WB) is a major topic of research across several scientific disciplines, partly driven by its strong association with psychological and mental health. Twin-family studies have found that both genotype and environment play an important role in explaining the variance in WB. Epigenetic mechanisms, such as DNA methylation, regulate gene expression, and may mediate genetic and environmental effects on WB. Here, for the first time, we apply an epigenome-wide association study (EWAS) approach to identify differentially methylated sites associated with individual differences in WB. Subjects were part of the longitudinal survey studies of the Netherlands Twin Register (NTR) and participated in the NTR biobank project between 2002 and 2011. WB was assessed by a short inventory that measures satisfaction with life (SAT). DNA methylation was measured in whole blood by the Illumina Infinium HumanMethylation450 BeadChip (HM450k array) and the association between WB and DNA methylation level was tested at 411,169 autosomal sites. Two sites (cg10845147, p = 1.51 * 10−8 and cg01940273, p = 2.34 * 10−8) reached genome-wide significance following Bonferonni correction. Four more sites (cg03329539, p = 2.76* 10−7; cg09716613, p = 3.23 * 10−7; cg04387347, p = 3.95 * 10−7; and cg02290168, p = 5.23 * 10−7) were considered to be genome-wide significant when applying the widely used criterion of a FDR q value < 0.05. Gene ontology (GO) analysis highlighted enrichment of several central nervous system categories among higher-ranking methylation sites. Overall, these results provide a first insight into the epigenetic mechanisms associated with WB and lay the foundations for future work aiming to unravel the biological mechanisms underlying a complex trait like WB.
Does Social Belonging to Primary Groups Protect Young People From the Effects of Pro-Suicide Sites?
Authors: Minkkinen Jaana , Oksanen Atte , Näsi Matti , Keipi Teo , Kaakinen Markus , Räsänen Pekka
Published: December 2015

Abstract. Background: The Internet has facilitated the existence of extreme and pathological communities that share information about ways to complete suicide or to deliberately harm or hurt oneself. This material is user-generated and easily accessible. Aims: The present study analyzed the buffering effect of social belonging to a primary group in the situation of pro-suicide site exposure. Method: Cross-national data were collected from the US, UK, Germany, and Finland in spring 2013 and 2014 from respondents aged 15–30 years (N = 3,567). Data were analyzed by using linear regression separately for women and men for each country. Results: A higher level of belonging to a primary group buffered the negative association of pro-suicide site exposure with mental health, measured as happiness, although the results were not consistent in the subgroups. US male subjects showed a significant buffering effect of the sense of belonging to family while the belonging to friends had a buffering effect among four other subgroups: British female and male subjects and Finnish female and male subjects. Conclusion: The results underline the positive potential of primary groups to shield young people’s mental health in the situation of pro-suicide site exposure.
A genome-wide IR-induced RAD51 foci RNAi screen identifies CDC73 involved in chromatin remodeling for DNA repair
Authors: Herr Patrick , Lundin Cecilia , Evers Bastiaan , Ebner Daniel , Bauerschmidt Christina , Kingham Guy , Palmai-Pallag Timea , Mortusewicz Oliver , Frings Oliver , Sonnhammer Erik , Helleday Thomas
Published: December 2015

To identify new regulators of homologous recombination repair, we carried out a genome-wide short-interfering RNA screen combined with ionizing irradiation using RAD51 foci formation as readout. All candidates were confirmed by independent short-interfering RNAs and validated in secondary assays like recombination repair activity and RPA foci formation. Network analysis of the top modifiers identified gene clusters involved in recombination repair as well as components of the ribosome, the proteasome and the spliceosome, which are known to be required for effective DNA repair. We identified and characterized the RNA polymerase II-associated protein CDC73/Parafibromin as a new player in recombination repair and show that it is critical for genomic stability. CDC73 interacts with components of the SCF/Cullin and INO80/NuA4 chromatin-remodeling complexes to promote Histone ubiquitination. Our findings indicate that CDC73 is involved in local chromatin decondensation at sites of DNA damage to promote DNA repair. This function of CDC73 is related to but independent of its role in transcriptional elongation.
Single‐cell technologies are revolutionizing the approach to rare cells
Authors: Proserpio Valentina , Lönnberg Tapio
Published: December 2015

In the last lustrum single‐cell techniques such as single‐cell quantitative PCR, RNA and DNA sequencing, and the state‐of‐the‐art cytometry by time of flight (CyTOF) mass cytometer have allowed a detailed analysis of the sub‐composition of different organs from the bone marrow hematopoietic compartment to the brain. These fine‐grained analyses have highlighted the great heterogeneity within each cell compartment revealing previously unknown subpopulations of cells. In this review, we analyze how this fast technological evolution has improved our understanding of the biological processes with a particular focus on rare cells of the immune system.
Privatization of cooperative benefits stabilizes mutualistic cross-feeding interactions in spatially structured environments
Authors: Pande Samay , Kaftan Filip , Lang Stefan , Svatoš Aleš , Germerodt Sebastian , Kost Christian
Published: December 2015

Metabolic cross-feeding interactions are ubiquitous in natural microbial communities. However, it remains generally unclear whether the production and exchange of metabolites incurs fitness costs to the producing cells and if so, which ecological mechanisms can facilitate a cooperative exchange of metabolites among unrelated individuals. We hypothesized that positive assortment within structured environments can maintain mutualistic cross-feeding. To test this, we engineered Acinetobacter baylyi and Escherichia coli to reciprocally exchange essential amino acids. Interspecific coculture experiments confirmed that non-cooperating types were selectively favoured in spatially unstructured (liquid culture), yet disfavoured in spatially structured environments (agar plates). Both an individual-based model and experiments with engineered genotypes indicated that a segregation of cross-feeders and non-cooperating auxotrophs stabilized cooperative cross-feeding in spatially structured environments. Chemical imaging confirmed that auxotrophs were spatially excluded from cooperative benefits. Together, these results demonstrate that cooperative cross-feeding between different bacterial species is favoured in structured environments such as bacterial biofilms, suggesting this type of interactions might be common in natural bacterial communities.
ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy
Authors: Albright Ronald A. , Stabach Paul , Cao Wenxiang , Kavanagh Dillon , Mullen Isabelle , Braddock Alexander A. , Covo Mariel S. , Tehan Martin , Yang Guangxiao , Cheng Zhiliang , Bouchard Keith , Yu Zhao-Xue , Thorn Stephanie , Wang Xiangning , Folta-Stogniew Ewa J. , Negrete Alejandro , Sinusas Albert J. , Shiloach Joseph , Zubal George , Madri Joseph A. , De La Cruz Enrique M. , Braddock Demetrios T.
Published: December 2015

Diseases of ectopic calcification of the vascular wall range from lethal orphan diseases such as generalized arterial calcification of infancy (GACI), to common diseases such as hardening of the arteries associated with aging and calciphylaxis of chronic kidney disease (CKD). GACI is a lethal orphan disease in which infants calcify the internal elastic lamina of their medium and large arteries and expire of cardiac failure as neonates, while calciphylaxis of CKD is a ubiquitous vascular calcification in patients with renal failure. Both disorders are characterized by vascular Mönckeburg’s sclerosis accompanied by decreased concentrations of plasma inorganic pyrophosphate (PPi). Here we demonstrate that subcutaneous administration of an ENPP1-Fc fusion protein prevents the mortality, vascular calcifications and sequela of disease in animal models of GACI, and is accompanied by a complete clinical and biomarker response. Our findings have implications for the treatment of rare and common diseases of ectopic vascular calcification.
A redox signalling globin is essential for reproduction in Caenorhabditis elegans
Authors: De Henau Sasha , Tilleman Lesley , Vangheel Matthew , Luyckx Evi , Trashin Stanislav , Pauwels Martje , Germani Francesca , Vlaeminck Caroline , Vanfleteren Jacques R. , Bert Wim , Pesce Alessandra , Nardini Marco , Bolognesi Martino , De Wael Karolien , Moens Luc , Dewilde Sylvia , Braeckman Bart P.
Published: December 2015

Moderate levels of reactive oxygen species (ROS) are now recognized as redox signalling molecules. However, thus far, only mitochondria and NADPH oxidases have been identified as cellular sources of ROS in signalling. Here we identify a globin (GLB-12) that produces superoxide, a type of ROS, which serves as an essential signal for reproduction in C. elegans. We find that GLB-12 has an important role in the regulation of multiple aspects in germline development, including germ cell apoptosis. We further describe how GLB-12 displays specific molecular, biochemical and structural properties that allow this globin to act as a superoxide generator. In addition, both an intra- and extracellular superoxide dismutase act as key partners of GLB-12 to create a transmembrane redox signal. Our results show that a globin can function as a driving factor in redox signalling, and how this signal is regulated at the subcellular level by multiple control layers.
The higher order auditory cortex is involved in the assignment of affective value to sensory stimuli
Authors: Grosso Anna , Cambiaghi Marco , Renna Annamaria , Milano Luisella , Roberto Merlo Giorgio , Sacco Tiziana , Sacchetti Benedetto
Published: December 2015

The sensory cortex participates in emotional memory but its role is poorly understood. Here we show that inactivation of the higher order auditory cortex Te2 in rats during early memory consolidation impairs remote first- and second-order fear memories but not the association between two neutral cues. Furthermore, Te2 inactivation prevents changes in the valence of such information. Following the presentation of two auditory cues previously paired with either pleasant or painful stimuli, a large percentage of cells responds to both experiences but also a small fraction of neurons responds exclusively to one of them. The latter type of neurons signals the valence rather than the salience or the motor responses associated with the stimuli, and reflects selective associative processes. Pharmacogenetic silencing of memory-activated neurons causes amnesia. Thus, Te2 represents a crucial node for the assignment of the affective value to sensory stimuli and for the storage of such information.
Social dynamics within decomposer communities lead to nitrogen retention and organic matter build-up in soils
Authors: Kaiser Christina , Franklin Oskar , Richter Andreas , Dieckmann Ulf
Published: December 2015

The chemical structure of organic matter has been shown to be only marginally important for its decomposability by microorganisms. The question of why organic matter does accumulate in the face of powerful microbial degraders is thus key for understanding terrestrial carbon and nitrogen cycling. Here we demonstrate, based on an individual-based microbial community model, that social dynamics among microbes producing extracellular enzymes (‘decomposers’) and microbes exploiting the catalytic activities of others (‘cheaters’) regulate organic matter turnover. We show that the presence of cheaters increases nitrogen retention and organic matter build-up by downregulating the ratio of extracellular enzymes to total microbial biomass, allowing nitrogen-rich microbial necromass to accumulate. Moreover, increasing catalytic efficiencies of enzymes are outbalanced by a strong negative feedback on enzyme producers, leading to less enzymes being produced at the community level. Our results thus reveal a possible control mechanism that may buffer soil CO2 emissions in a future climate.
Ion exchanger in the brain: Quantitative analysis of perineuronally fixed anionic binding sites suggests diffusion barriers with ion sorting properties
Authors: Morawski Markus , Reinert Tilo , Meyer-Klaucke Wolfram , Wagner Friedrich E. , Tröger Wolfgang , Reinert Anja , Jäger Carsten , Brückner Gert , Arendt Thomas
Published: December 2015

Perineuronal nets (PNs) are a specialized form of brain extracellular matrix, consisting of negatively charged glycosaminoglycans, glycoproteins and proteoglycans in the direct microenvironment of neurons. Still, locally immobilized charges in the tissue have not been accessible so far to direct observations and quantifications. Here, we present a new approach to visualize and quantify fixed charge-densities on brain slices using a focused proton-beam microprobe in combination with ionic metallic probes. For the first time, we can provide quantitative data on the distribution and net amount of pericellularly fixed charge-densities, which, determined at 0.4–0.5 M, is much higher than previously assumed. PNs, thus, represent an immobilized ion exchanger with ion sorting properties high enough to partition mobile ions in accord with Donnan-equilibrium. We propose that fixed charge-densities in the brain are involved in regulating ion mobility, the volume fraction of extracellular space and the viscosity of matrix components.
Tuning of nanoparticle biological functionality through controlled surface chemistry and characterisation at the bioconjugated nanoparticle surface
Authors: Hristov Delyan R. , Rocks Louise , Kelly Philip M. , Thomas Steffi S. , Pitek Andrzej S. , Verderio Paolo , Mahon Eugene , Dawson Kenneth A.
Published: December 2015

We have used a silica – PEG based bionanoconjugate synthetic scheme to study the subtle connection between cell receptor specific recognition and architecture of surface functionalization chemistry. Extensive physicochemical characterization of the grafted architecture is capable of capturing significant levels of detail of both the linker and grafted organization, allowing for improved reproducibility and ultimately insight into biological functionality. Our data suggest that scaffold details, propagating PEG layer architecture effects, determine not only the rate of uptake of conjugated nanoparticles into cells but also, more significantly, the specificity of pathways via which uptake occurs.
Protein profiling reveals consequences of lifestyle choices on predicted biological aging
Authors: Enroth Stefan , Enroth Sofia Bosdotter , Johansson Åsa , Gyllensten Ulf
Published: December 2015

Ageing is linked to a number of changes in how the body and its organs function. On a molecular level, ageing is associated with a reduction of telomere length, changes in metabolic and gene-transcription profiles and an altered DNA-methylation pattern. Lifestyle factors such as smoking or stress can impact some of these molecular processes and thereby affect the ageing of an individual. Here we demonstrate by analysis of 77 plasma proteins in 976 individuals, that the abundance of circulating proteins accurately predicts chronological age, as well as anthropometrical measurements such as weight, height and hip circumference. The plasma protein profile can also be used to identify lifestyle factors that accelerate and decelerate ageing. We found smoking, high BMI and consumption of sugar-sweetened beverages to increase the predicted chronological age by 2–6 years, while consumption of fatty fish, drinking moderate amounts of coffee and exercising reduced the predicted age by approximately the same amount. This method can be applied to dried blood spots and may thus be useful in forensic medicine to provide basic anthropometrical measures for an individual based on a biological evidence sample.
Deterministic Tractography of the Nigrostriatal-Nigropallidal Pathway in Parkinson’s Disease
Authors: Tan Wen-Qi , Yeoh Chooi-Sum , Rumpel Helmut , Nadkarni Nivedita , Lye Weng-Kit , Tan Eng-King , Chan Ling-Ling
Published: December 2015

We hypothesized that deterministic tractography is practical and sensitive to changes in the complex nigrostriatal and nigropallidal pathway (NSP) in Parkinson’s disease (PD). Using diffusion tensor imaging (DTI) tractography, we investigated the NSP to evaluate differences between PD patients and controls and examined their clinico-radiologic correlation. Structural and DTI brain scans were obtained in 40 subjects (21 PD patients and 19 healthy controls). We isolated the NSP using a user-friendly DTI toolkit based on deterministic brute-force tractography. DTI parameters of fractional anisotropy (FA), mean, axial and radial diffusivity and streamline count of the NSP were measured. Average FA (p < 0.01) and streamline count (p < 0.001) were significantly lower in the PD compared to control group. Mean diffusivity and radial diffusivity were significantly higher in the PD group (p < 0.05). Average streamline count correlated with the United Parkinson’s Disease Rating Scale motor score (p < 0.05). Point-to-point FA profiles of the tract demonstrated peak divergence between PD and control towards the tract midpoint rather than the distal grey matter. Our findings demonstrated a clinically and radiologically practical application of DTI tractography to the NSP in PD, without requiring complex imaging sequences for anatomical localization or segmentation software.
Systolic aortic pressure-time area is a useful index describing arterial wave properties in rats with diabetes
Authors: Chang Ru-Wen , Chang Chun-Yi , Wu Ming-Shiou , Yu Hsi-Yu , Luo Jian-Ming , Chen Yih-Sharng , Lin Fang-Yue , Lai Liang-Chuan , Wang Chih-Hsien , Chang Kuo-Chu
Published: December 2015

The accurate measurement of arterial wave properties in terms of arterial wave transit time (τw) and wave reflection factor (Rf) requires simultaneous records of aortic pressure and flow signals. However, in clinical practice, it will be helpful to describe the pulsatile ventricular afterload using less-invasive parameters if possible. We investigated the possibility of systolic aortic pressure-time area (PTAs), calculated from the measured aortic pressure alone, acting as systolic workload imposed on the rat diabetic heart. Arterial wave reflections were derived using the impulse response function of the filtered aortic input impedance spectra. The cardiovascular condition in the rats with either type 1 or type 2 diabetes was characterized by (1) an elevation in PTAs; and (2) an increase in Rf and decrease in τw. We found that an inverse linear correlation between PTAs and arterial τw reached significance (τw = 38.5462 − 0.0022 × PTAs; r = 0.7708, P < 0.0001). By contrast, as the PTAs increased, the reflection intensity increased: Rf = –0.5439 + 0.0002 × PTAs; r = 0.8701; P <0 .0001. All these findings suggested that as diabetes stiffened aortas, the augmented aortic PTAs might act as a useful index describing the diabetes-related deterioration in systolic ventricular workload.
The potential for carbon bio-sequestration in China’s paddy rice (Oryza sativa L.) as impacted by slag-based silicate fertilizer
Authors: Song Alin , Ning Dongfeng , Fan Fenliang , Li Zhaojun , Provance-Bowley Mary , Liang Yongchao
Published: December 2015

Rice is a typical silicon-accumulating plant. Silicon (Si), deposited as phytoliths during plant growth, has been shown to occlude organic carbon, which may prove to have significant effects on the biogeochemical sequestration of atmospheric CO2. This study evaluated the effects of silicate fertilization on plant Si uptake and carbon bio-sequestration in field trials on China’s paddy soils. The results showed (1) Increased Si concentrations in rice straw with increasing application rates of silicate fertilizer; (2) Strong positive correlations between phytolith contents and straw SiO2 contents and between phytolith contents and phytolith-occluded carbon (PhytOC) contents in rice straw; (3) Positive correlations between the phytolith production flux and either the above-ground net primary productivity (ANPP) or the PhytOC production rates; (4) Increased plant PhytOC storage with increasing application rates of silicate fertilizer. The average above-ground PhytOC production rates during China’s rice production are estimated at 0.94 × 106 tonnes CO2 yr−1 without silicate fertilizer additions. However, the potential exists to increase PhytOC levels to 1.16–2.17 × 106 tonnes CO2 yr−1 with silicate fertilizer additions. Therefore, providing silicate fertilizer during rice production may serve as an effective tool in improving atmospheric CO2 sequestration in global rice production areas.
Relation between bandgap and resistance drift in amorphous phase change materials
Authors: Rütten Martin , Kaes Matthias , Albert Andreas , Wuttig Matthias , Salinga Martin
Published: December 2015

Memory based on phase change materials is currently the most promising candidate for bridging the gap in access time between memory and storage in traditional memory hierarchy. However, multilevel storage is still hindered by the so-called resistance drift commonly related to structural relaxation of the amorphous phase. Here, we present the temporal evolution of infrared spectra measured on amorphous thin films of the three phase change materials Ag4In3Sb67Te26, GeTe and the most popular Ge2Sb2Te5. A widening of the bandgap upon annealing accompanied by a decrease of the optical dielectric constant ε∞ is observed for all three materials. Quantitative comparison with experimental data for the apparent activation energy of conduction reveals that the temporal evolution of bandgap and activation energy can be decoupled. The case of Ag4In3Sb67Te26, where the increase of activation energy is significantly smaller than the bandgap widening, demonstrates the possibility to identify new phase change materials with reduced resistance drift.
Development of Alendronate-conjugated Poly (lactic-co-glycolic acid)-Dextran Nanoparticles for Active Targeting of Cisplatin in Osteosarcoma
Authors: Liu Ping , Sun Liang , Zhou Dong-sheng , Zhang Peng , Wang Yong-hui , Li Dong , Li Qing-hu , Feng Rong-jie
Published: December 2015

In this study, we developed a novel poly (lactic-co-glycolic acid)-dextran (PLD)-based nanodelivery system to enhance the anticancer potential of cisplatin (CDDP) in osteosarcoma cells. A nanosized CDDP-loaded PLGA-DX nanoparticle (PLD/CDDP) controlled the release rate of CDDP up to 48 h. In vitro cytotoxicity assay showed a superior anticancer effect for PLD/CDDP and with an appreciable cellular uptake via endocytosis-mediated pathways. PLD/CDDP exhibited significant apoptosis of MG63 cancer cells compared to that of free CDDP. Approximately ~25% of cells were in early apoptosis phase after PLD/CDDP treatment comparing to ~15% for free CDDP after 48h incubation. Similarly, PLD/CDDP exhibited ~30% of late apoptosis cells comparing to only ~8% for free drug treatment. PLD/CDDP exhibited significantly higher G2/M phase arrest in MG63 cells than compared to free CDDP with a nearly 2-fold higher arrest in case of PLD/CDDP treated group (~60%). Importantly, PLD/CDDP exhibited a most significant anti-tumor activity with maximum tumor growth inhibition. The superior inhibitory effect was further confirmed by a marked reduction in the number of CD31 stained tumor blood vessels and decrease in the Ki67 staining intensity for PLD/CDDP treated animal group. Overall, CDDP formulations could provide a promising and most effective platform in the treatment of osteosarcoma.
Facile Synthesis of Coaxial CNTs/MnOx-Carbon Hybrid Nanofibers and Their Greatly Enhanced Lithium Storage Performance
Authors: Yang Zunxian , Lv Jun , Pang Haidong , Yan Wenhuan , Qian Kun , Guo Tailiang , Guo Zaiping
Published: December 2015

Carbon nanotubes (CNTs)/MnOx-Carbon hybrid nanofibers have been successfully synthesized by the combination of a liquid chemical redox reaction (LCRR) and a subsequent carbonization heat treatment. The nanostructures exhibit a unique one-dimensional core/shell architecture, with one-dimensional CNTs encapsulated inside and a MnOx-carbon composite nanoparticle layer on the outside. The particular porous characteristics with many meso/micro holes/pores, the highly conductive one-dimensional CNT core, as well as the encapsulating carbon matrix on the outside of the MnOxnanoparticles, lead to excellent electrochemical performance of the electrode. The CNTs/MnOx-Carbon hybrid nanofibers exhibit a high initial reversible capacity of 762.9 mAhg−1, a high reversible specific capacity of 560.5 mAhg−1after 100 cycles and excellent cycling stability and rate capability, with specific capacity of 396.2 mAhg−1when cycled at the current density of 1000 mAg−1, indicating that the CNTs/MnOx-Carbon hybrid nanofibers are a promising anode candidate for Li-ion batteries.
Synthesis of nanocrystals by discharges in liquid nitrogen from Si–Sn sintered electrode
Authors: Kabbara H. , Noël C. , Ghanbaja J. , Hussein K. , Mariotti D. , Švrček V. , Belmonte T.
Published: December 2015

The synthesis feasibility of silicon–tin nanocrystals by discharges in liquid nitrogen is studied using a Si–10 at % Sn sintered electrode. Time-resolved optical emission spectroscopy shows that silicon and tin melt almost simultaneously. The presence of both vapours does not lead to the synthesis of alloyed nanocrystals but to the synthesis of separate nanocrystals of silicon and tin with average sizes of 10 nm. These nanocrystals are transformed into amorphous silicon oxide (am–SiO2) and β–SnO2 by air oxidation, after evaporation of the liquid nitrogen. The synthesis of an am-Si0.95Sn0.05 phase around large silicon crystals (~500 nm) decorated by β–Sn spheroids is achieved if the current flowing through electrodes is high enough. When the sintered electrode is hit by powerful discharges, some grains are heated and tin diffuses in the large silicon crystals. Next, these grains are shelled and fall into the dielectric liquid.
Adaptation to sustained nitrogen starvation by Escherichia coli requires the eukaryote-like serine/threonine kinase YeaG
Authors: Figueira Rita , Brown Daniel R. , Ferreira Delfim , Eldridge Matthew J. G. , Burchell Lynn , Pan Zhensheng , Helaine Sophie , Wigneshweraraj Sivaramesh
Published: December 2015

The Escherichia coli eukaryote-like serine/threonine kinase, encoded by yeaG, is expressed in response to diverse stresses, including nitrogen (N) starvation. A role for yeaG in bacterial stress response is unknown. Here we reveal for the first time that wild-type E. coli displays metabolic heterogeneity following sustained periods of N starvation, with the metabolically active population displaying compromised viability. In contrast, such heterogeneity in metabolic activity is not observed in an E. coli ∆yeaG mutant, which continues to exist as a single and metabolically active population and thus displays an overall compromised ability to survive sustained periods of N starvation. The mechanism by which yeaG acts, involves the transcriptional repression of two toxin/antitoxin modules, mqsR/mqsA and dinJ/yafQ. This, consequently, has a positive effect on the expression of rpoS, the master regulator of the general bacterial stress response. Overall, results indicate that yeaG is required to fully execute the rpoS-dependent gene expression program to allow E. coli to adapt to sustained N starvation and unravels a novel facet to the regulatory basis that underpins adaptive response to N stress.
Inhibition of NF-κB by deoxycholic acid induces miR-21/PDCD4-dependent hepatocellular apoptosis
Authors: Rodrigues Pedro M. , Afonso Marta B. , Simão André L. , Borralho Pedro M. , Rodrigues Cecília M. P. , Castro Rui E.
Published: December 2015

MicroRNAs (miRNAs/miRs) are key regulators of liver metabolism, while toxic bile acids participate in the development of several liver diseases. We previously demonstrated that deoxycholic acid (DCA), a cytotoxic bile acid implicated in the pathogenesis of non-alcoholic fatty liver disease, inhibits miR-21 expression in hepatocytes. Here, we investigated the mechanisms by which DCA modulates miR-21 and whether miR-21 contributes for DCA-induced cytotoxicity. DCA inhibited miR-21 expression in primary rat hepatocytes in a dose-dependent manner and increased miR-21 pro-apoptotic target programmed cell death 4 (PDCD4) and apoptosis. Both miR-21 overexpression and PDCD4 silencing hampered DCA-induced cell death. Further, DCA decreased NF-κB activity, shown to represent an upstream mechanism leading to modulation of the miR-21/PDCD4 pathway. In fact, NF-κB overexpression or constitutive activation halted miR-21-dependent apoptosis by DCA while opposite results were observed upon NF-κB inhibition. In turn, DCA-induced oxidative stress resulted in caspase-2 activation and NF-κB/miR-21 inhibition, in a PIDD-dependent manner. Finally, modulation of the NF-κB/miR-21/PDCD4 pro-apoptotic pathway by DCA was also shown to occur in the rat liverin vivo. These signalling circuits may constitute appealing targets for bile acid-associated liver pathologies.
Influence of age, gender and race on nitric oxide release over acupuncture points-meridians
Authors: Ma Sheng-Xing , Lee Paul C. , Jiang Isabelle , Ma Eva , Hu Jay S. , Li Xi-Yan
Published: December 2015

This study examined the influence of age, gender and race on nitric oxide (NO) release over acupuncture points, meridian without acupoint and non-meridian regions of the Pericardium (PC) and Bladder (BL) meridian as well as aging on LU meridian in 61 healthy subjects. Biocapture tubes were attached to the skin surface and total nitrite and nitrate was biocaptured and quantified using chemiluminescence. In elder ages compared to adults, NO levels over the ventral forearm were significantly decreased over LU on radial regions but not altered over PC on medial regions. Conversely, NO content was elevated over BL regions only in overweight/obesity of elder ages. NO levels over PC regions were marginally elevated in overweight/obese males compared to females but did not alter between races. These results suggest a selective reduction of NO release over LU meridian with aging, which is consistent with a progressive decline in lung function and increase in chronic respiratory disease in elder ages. Increased NO levels along the BL meridian in older obese subjects may reflect a modified NO level along somatic-bladder pathway for counteracting bladder dysfunctions with aging. Both of them support somatic-organ connections in the meridian system associated with potential pathophysiological changes with aging.