bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship of Lutein and Zeaxanthin Levels to Neurocognitive Functioning: An fMRI Study of Older Adults
Authors: Lindbergh Cutter A. , Mewborn Catherine M. , Hammond Billy R. , Renzi-Hammond Lisa M. , Curran-Celentano Joanne M. , Miller L. Stephen
Published: October 2016

Objectives:It is well known that the carotenoids lutein (L) and zeaxanthin (Z) improve eye health and an accumulating evidence base suggests cognitive benefits as well. The present study investigated underlying neural mechanisms using functional magnetic resonance imaging (fMRI). It was hypothesized that lower L and Z concentrations would be associated with neurobiological inefficiency (i.e., increased activation) during cognitive performance.Methods:Forty-three community-dwelling older adults (mean age=72 years; 58% female; 100% Caucasian) were asked to learn and recall pairs of unrelated words in an fMRI-adapted paradigm. L and Z levels were measured in retina (macular pigment optical density) and serum using validated procedures.Results:Following first-level contrasts of encoding and retrieval trials minus control trials (p<.05, family-wise error corrected, minimum voxel cluster=8), L and Z were found to significantly and negatively relate to blood-oxygen-level-dependent signal in central and parietal operculum cortex, inferior frontal gyrus, supramarginal gyrus, planum polare, frontal and middle temporal gyrus, superior parietal lobule, postcentral gyrus, precentral gyrus, occipital cortex bilaterally, and cerebellar regions.Conclusions:To the authors’ knowledge, the present study represents the first attempt to investigate neural mechanisms underlying the relation of L and Z to cognition using fMRI. The observed results suggest that L and Z promote cognitive functioning in old age by enhancing neural efficiency. (JINS, 2017,23, 11–22)
I was sat there talking all night: a corpus-based study on factors governing intra-dialectal variation in British English
Authors: STANGE ULRIKE
Published: October 2016

When it comes to intra-dialectal variation, the factors governing the choice between functionally equivalent variants still require an exhaustive analysis. The construction be sat/be stood with progressive meaning alternates with the standard form be sitting/be standing in a number of British English dialects. The present article investigates to what extent the Complexity Principle (see Rohdenburg 1996) and horror aequi (see Rohdenburg 2003) influence the choice between so-called pseudo-passive and progressive constructions. Empirical analyses of spoken data in the British National Corpus reveal that this variation phenomenon is common in dialects of Northern and Southwest England, and to a lesser degree in the Midlands and in London. Moreover, we find considerable differences in the distribution of these pseudo-passives regarding their relative frequency and the number of dialects that make use of them. Drawing on a total of 106 occurrences for the construction be stood vs be standing and 366 for be sat vs be sitting, the article evaluates how far the principles above can be considered as statistically significant determinants of intra-dialectal variation. To this end, it will be essential to test for other factors potentially influencing the choice of dialectal variants, such as age and gender.
Form does not follow function, but variation does: the origin and early usage of possessive havegot in English
Authors: LORENZ DAVID
Published: October 2016

This article investigates the emergence and early use of possessive havegot in English. Two hypotheses about its emergence are tested on historical data (c.1460–1760). One hypothesis is based on communicative functionality, suggesting that got was inserted as a ‘pattern preserver’ to compensate for the increased reduction of have. The other hypothesis invokes the conventionalization of an invited inference, thus a (non-functional) semantic shift which does not immediately serve to support a communicative function. The diachronic evidence is found to support only the latter hypothesis.

In the second part the early stage of the variation of have and havegot is investigated (c.1720–50). The results show a strong register difference, but also a division of labour between the variants that can be explained by the syntactic and semantic properties of havegot as having emerged out of a present perfect of get. Thus, the variation is organized in a functionally motivated way.

It is concluded that in the development of possessive havegot functional constraints apply to the variation early on, but do not play an evident role in the emergence of the new variant. This suggests that functional motivations are a directing force but not necessarily a driving force in language change.
Variation across two dimensions: testing the Complexity Principle and the Uniform Information Density Principle on adjectival data
Authors: KAATARI HENRIK
Published: October 2016

This study tests the applicability of the Complexity Principle (Rohdenburg 1996) and the Uniform Information Density Principle (Jaeger 2010) on adjectival data as regards the variation between retaining and omitting the complementizer that in English adjectival complementation constructions. More specifically, the study tests the effect of different factors of potential importance on this variation across extraposed (e.g. It was inevitable (that) he should be nicknamed ‘the Ferret’) and post-predicate clauses (e.g. I'm happy (that) we are married). While both the factors concerned with the Complexity Principle and the Uniform Information Density Principle are found to have an effect on post-predicate clauses, less clear effects are found concerning extraposed clauses. I attribute these findings to the difference between the two constructions in terms of their frequency of co-occurrence with different matrix subject types and with different adjectives.
Kant as Both Conceptualist and Nonconceptualist
Authors: Golob Sacha
Published: October 2016

This article advances a new account of Kant’s views on conceptualism. On the one hand, I argue that Kant was a nonconceptualist. On the other hand, my approach accommodates many motivations underlying the conceptualist reading of his work: for example, it is fully compatible with the success of the Transcendental Deduction. I motivate my view by providing a new analysis of both Kant’s theory of perception and of the role of categorical synthesis: I look in particular at the categories of quantity. Locating my interpretation in relation to recent research by Allais, Ginsborg, Tolley and others, I argue that it offers an attractive compromise on this important theoretical and exegetical issue.
‘Total Transformation’: Why Kant Did Not Give up on Education
Authors: Louden Robert B.
Published: October 2016

In this essay I argue that Kant remained committed to the necessity and fundamental importance of education throughout his career. Like Johann Bernhard Basedow (1724–90), Kant holds that a ‘total transformation’ of schools is necessary, and he holds this view not only in the 1770s but in his later years as well. In building my case I try to refute two recent opposing interpretations – Reinhard Brandt’s position that Kant’s early ‘education enthusiasm’ was later replaced by a politics enthusiasm, and Manfred Kuehn’s view that the increasing importance of autonomy in Kant’s mature ethics leads him to de-emphasize education.
The Asymmetry of Space: Kant’s Theory of Absolute Space in 1768
Authors: Rukgaber Matthew S.
Published: October 2016

I propose that we interpret Kant’s argument from incongruent counterparts in the 1768 article ‘Concerning the Ultimate Ground of the Differentiation of Directions in Space’ in light of a theory of dynamic absolute space that he accepted throughout the 1750s and 1760s. This force-based or material conception of space was not an unusual interpretation of the Newtonian notion of absolute space. Nevertheless, commentators have continually argued that Kant’s argument is an utter failure that shifts from the metaphysics of space to its epistemology, because he has no way to connect ‘directionality’ and ‘handedness’ to absolute space. This supposed failure is based on an understanding of absolute space in purely mathematical terms and as an absolute void that lacks any qualitative or dynamic features. If we recognize that Kant held that space had an intrinsic directional asymmetry then his argument successfully connects incongruent counterparts to absolute space. The presence of this notion in Kant’s pre-Critical thought is rarely noted, and its necessity in understanding his incongruence argument is novel.
Empirical Cognition in the Transcendental Deduction: Kant’s Starting Point and his Humean Problem
Authors: Sommerlatte Curtis
Published: October 2016

In this article, I argue that in the sense of greatest epistemological concern for Kant, empirical cognition is ‘rational sensory discrimination’: the identification or differentiation of sensory objects from each other (whether correctly or not), occurring through a capacity of forming judgements (whether correct or not). With this account of empirical cognition, I show how the Transcendental Deduction of the firstCritiqueis most plausibly read as having as its fundamental assumption the thesis that we have empirical cognition, and I provide evidence that Kant understood Hume as granting this assumption.
SOME INFINITE PERMUTATION GROUPS AND RELATED FINITE LINEAR GROUPS
Authors: NEUMANN PETER M. , PRAEGER CHERYL E. , SMITH SIMON M.
Published: October 2016

This article began as a study of the structure of infinite permutation groups $G$ in which point stabilisers are finite and all infinite normal subgroups are transitive. That led to two variations. One is the generalisation in which point stabilisers are merely assumed to satisfy min-n, the minimal condition on normal subgroups. The groups $G$ are then of two kinds. Either they have a maximal finite normal subgroup, modulo which they have either one or two minimal nontrivial normal subgroups, or they have a regular normal subgroup $M$ which is a divisible abelian $p$-group of finite rank. In the latter case the point stabilisers are finite and act irreducibly on a $p$-adic vector space associated with $M$. This leads to our second variation, which is a study of the finite linear groups that can arise.
REPRESENTING CONJUNCTIVE DEDUCTIONS BY DISJUNCTIVE DEDUCTIONS
Authors: DOŠEN KOSTA , PETRIĆ ZORAN
Published: October 2016

A skeleton of the category with finite coproducts${\cal D}$ freely generated by a single object has a subcategory isomorphic to a skeleton of the category with finite products ${\cal C}$ freely generated by a countable set of objects. As a consequence, we obtain that ${\cal D}$ has a subcategory equivalent with ${\cal C}$. From a proof-theoretical point of view, this means that up to some identifications of formulae the deductions of pure conjunctive logic with a countable set of propositional letters can be represented by deductions in pure disjunctive logic with just one propositional letter. By taking opposite categories, one can replace coproduct by product, i.e., disjunction by conjunction, and the other way round, to obtain the dual results.
Validity of recalled v. recorded birth weight: a systematic review and meta-analysis
Authors: Shenkin S. D. , Zhang M. G. , Der G. , Mathur S. , Mina T. H. , Reynolds R. M.
Published: October 2016

Low birth weight is associated with adverse health outcomes. If birth weight records are not available, studies may use recalled birth weight. It is unclear whether this is reliable. We performed a systematic review and meta-analysis of studies comparing recalled with recorded birth weights. We followed the Meta-Analyses of Observational Studies in Epidemiology (MOOSE) statement and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched MEDLINE, EMBASE and Cumulative Index to Nursing and Allied Health Literature (CINAHL) to May 2015. We included studies that reported recalled birth weight and recorded birth weight. We excluded studies investigating a clinical population. Two reviewers independently reviewed citations, extracted data, assessed risk of bias. Data were pooled in a random effects meta-analysis for correlation and mean difference. In total, 40 studies were eligible for qualitative synthesis (n=78,997 births from 78,196 parents). Agreement between recalled and recorded birth weight was high: pooled estimate of correlation in 23 samples from 19 studies (n=7406) was 0.90 [95% confidence interval (CI) 0.87–0.93]. The difference between recalled and recorded birth weight in 29 samples from 26 studies (n=29,293) was small [range −86–129 g; random effects estimate 1.4 g (95% CI −4.0–6.9 g)]. Studies were heterogeneous, with no evidence for an effect of time since birth, person reporting, recall bias, or birth order. In post-hoc subgroup analysis, recall was higher than recorded birth weight by 80 g (95% CI 57–103 g) in low and middle income countries. In conclusion, there is high agreement between recalled and recorded birth weight. If birth weight is recalled, it is suitable for use in epidemiological studies, at least in high income countries.
Twinning and Multiple Birth Rates According to Maternal Age in the City of São Paulo, Brazil: 2003–2014
Authors: Otta Emma , Fernandes Eloisa de S. , Acquaviva Tiziana G. , Lucci Tania K. , Kiehl Leda C. , Varella Marco A. C. , Segal Nancy L. , Valentova Jaroslava V.
Published: October 2016

The present study investigates the twinning rates in the city of São Paulo, Brazil, during the years 2003–2014. The data were drawn from the Brazilian Health Department database ofSistema de Informações de Nascidos Vivos de São Paulo—SINASC(Live Births Information System of São Paulo). In general, more information is available on the incidence of twinning in developed countries than in developing ones. A total of 24,589 twin deliveries and 736 multiple deliveries were registered in 140 hospitals of São Paulo out of a total of 2,056,016 deliveries during the studied time period. The overall average rates of singleton, twin, and multiple births per 1,000 maternities (‰) were 987.43, 11.96 (dizygotic (DZ) rate was 7.15 and monozygotic (MZ) 4.42), and 0.36, respectively. We further regressed maternal age and historical time period on percentage of singleton, twin, and multiple birth rates. Our results indicated that maternal age strongly positively predicted twin and multiple birth rates, and negatively predicted singleton birth rates. The historical time period also positively, although weakly, predicted twin birth rates, and had no effect on singleton or multiple birth rates. Further, after applying Weinberg's differential method, we computed regressions separately for the estimated frequencies of DZ and MZ twin rates. DZ twinning was strongly positively predicted by maternal age and, to a smaller degree, by time period, while MZ twinning increased marginally only with higher maternal age. Factors such as increasing body mass index or air pollution can lead to the slight historical increase in DZ twinning rates. Importantly, consistent with previous cross-cultural and historical research, our results support the existence of an age-dependent physiological mechanism that leads to a strong increase in twinning and multiple births, but not singleton births, among mothers of higher age categories. From the ultimate perspective, twinning and multiple births in later age can lead to higher individual reproductive success near the end of the reproductive career of the mother.
Spencer Receives 2016 Whipple Award
Authors:   AGU
Published: October 2016

John Spencer will receive the 2016 Whipple Award at the 2016 American Geophysical Union Fall Meeting, to be held 12–16 December in San Francisco, Calif. The award recognizes an individual who has made an outstanding contribution in the field of planetary science.
U.S. Winter Outlook Sees No Drought Relief
Authors: Lemonick Sam
Published: October 2016

A weak La Niña is expected to further dry out southwestern and Gulf Coast states.
25-hydroxycholesterol contributes to cerebral inflammation of X-linked adrenoleukodystrophy through activation of the NLRP3 inflammasome
Authors: Jang Jiho , Park Sangjun , Jin Hur Hye , Cho Hyun-Ju , Hwang Inhwa , Pyo Kang Yun , Im Isak , Lee Hyunji , Lee Eunju , Yang Wonsuk , Kang Hoon-Chul , Won Kwon Sung , Yu Je-Wook , Kim Dong-Wook
Published: October 2016

X-linked adrenoleukodystrophy (X-ALD), caused by an ABCD1 mutation, is a progressive neurodegenerative disorder associated with the accumulation of very long-chain fatty acids (VLCFA). Cerebral inflammatory demyelination is the major feature of childhood cerebral ALD (CCALD), the most severe form of ALD, but its underlying mechanism remains poorly understood. Here, we identify the aberrant production of cholesterol 25-hydroxylase (CH25H) and 25-hydroxycholesterol (25-HC) in the cellular context of CCALD based on the analysis of ALD patient-derived induced pluripotent stem cells and ex vivo fibroblasts. Intriguingly, 25-HC, but not VLCFA, promotes robust NLRP3 inflammasome assembly and activation via potassium efflux-, mitochondrial reactive oxygen species (ROS)- and liver X receptor (LXR)-mediated pathways. Furthermore, stereotaxic injection of 25-HC into the corpus callosum of mouse brains induces microglial recruitment, interleukin-1β production, and oligodendrocyte cell death in an NLRP3 inflammasome-dependent manner. Collectively, our results indicate that 25-HC mediates the neuroinflammation of X-ALD via activation of the NLRP3 inflammasome.
Nlrp12 mutation causes C57BL/6J strain-specific defect in neutrophil recruitment
Authors: Ulland Tyler K. , Jain Nidhi , Hornick Emma E. , Elliott Eric I. , Clay Gwendolyn M. , Sadler Jeffrey J. , Mills Kathleen A. M. , Janowski Ann M. , Volk A. Paige Davis , Wang Kai , Legge Kevin L. , Gakhar Lokesh , Bourdi Mohammed , Ferguson Polly J. , Wilson Mary E. , Cassel Suzanne L. , Sutterwala Fayyaz S.
Published: October 2016

The inbred mouse strain C57BL/6J is widely used in models of immunological and infectious diseases. Here we show that C57BL/6J mice have a defect in neutrophil recruitment to a range of inflammatory stimuli compared with the related C57BL/6N substrain. This immune perturbation is associated with a missense mutation in Nlrp12 in C57BL/6J mice. Both C57BL/6J and NLRP12-deficient mice have increased susceptibility to bacterial infection that correlates with defective neutrophil migration. C57BL/6J and NLRP12-deficient macrophages have impaired CXCL1 production and the neutrophil defect observed in C57BL/6J and NLRP12-deficient mice is rescued by restoration of macrophage NLRP12. These results demonstrate that C57BL/6J mice have a functional defect in NLRP12 and that macrophages require NLRP12 expression for effective recruitment of neutrophils to inflammatory sites.
Surface uplift in the Central Andes driven by growth of the Altiplano Puna Magma Body
Authors: Perkins Jonathan P. , Ward Kevin M. , de Silva Shanaka L. , Zandt George , Beck Susan L. , Finnegan Noah J.
Published: October 2016

The Altiplano-Puna Magma Body (APMB) in the Central Andes is the largest imaged magma reservoir on Earth, and is located within the second highest orogenic plateau on Earth, the Altiplano-Puna. Although the APMB is a first-order geologic feature similar to the Sierra Nevada batholith, its role in the surface uplift history of the Central Andes remains uncertain. Here we show that a long-wavelength topographic dome overlies the seismically measured extent of the APMB, and gravity data suggest that the uplift is isostatically compensated. Isostatic modelling of the magmatic contribution to dome growth yields melt volumes comparable to those estimated from tomography, and suggests that the APMB growth rate exceeds the peak Cretaceous magmatic flare-up in the Sierran batholith. Our analysis reveals that magmatic addition may provide a contribution to surface uplift on par with lithospheric removal, and illustrates that surface topography may help constrain the magnitude of pluton-scale melt production.
Pan-cancer transcriptomic analysis associates long non-coding RNAs with key mutational driver events
Authors: Ashouri Arghavan , Sayin Volkan I. , Van den Eynden Jimmy , Singh Simranjit X. , Papagiannakopoulos Thales , Larsson Erik
Published: October 2016

Thousands of long non-coding RNAs (lncRNAs) lie interspersed with coding genes across the genome, and a small subset has been implicated as downstream effectors in oncogenic pathways. Here we make use of transcriptome and exome sequencing data from thousands of tumours across 19 cancer types, to identify lncRNAs that are induced or repressed in relation to somatic mutations in key oncogenic driver genes. Our screen confirms known coding and non-coding effectors and also associates many new lncRNAs to relevant pathways. The associations are often highly reproducible across cancer types, and while many lncRNAs are co-expressed with their protein-coding hosts or neighbours, some are intergenic and independent. We highlight lncRNAs with possible functions downstream of the tumour suppressor TP53 and the master antioxidant transcription factor NFE2L2. Our study provides a comprehensive overview of lncRNA transcriptional alterations in relation to key driver mutational events in human cancers.
The role of fivefold symmetry in suppressing crystallization
Authors: Taffs Jade , Patrick Royall C.
Published: October 2016

Although long assumed to have an important role in the suppression of crystallization and the development of glassformers, the effect of local fivefold symmetry has never been directly tested. Here we consider whether such suppression of crystallization has a kinetic or thermodynamic nature and investigate its mechanism. We introduce a model in which the degree of fivefold symmetry can be tuned by favouring arrangements of particles in pentagonal bipyramids. We thus show that fivefold symmetry has both kinetic and thermodynamic effects on the mechanism of crystallization to a face-centred cubic crystal. Our results suggest that the mechanism of crystallization suppression is related to the surface tension between fluid and crystal. Interestingly, the degree of fivefold symmetry has little effect on crystal growth rate, suggesting that growth may be only weakly coupled to fluid structure in hard sphere like systems. Upon increasing the fivefold symmetry, we find a first-order transition to an alternative icosahedra-rich phase. At intermediate bias strengths we find a one-component glassformer.
Robust homology-directed repair within mouse mammary tissue is not specifically affected by Brca2 mutation
Authors: Kass Elizabeth M. , Lim Pei Xin , Helgadottir Hildur R. , Moynahan Mary Ellen , Jasin Maria
Published: October 2016

The mammary gland undergoes significant proliferative stages after birth, but little is known about how the developmental changes impact DNA double-strand break (DSB) repair. Mutations in multiple genes involved in homology-directed repair (HDR), considered a particularly accurate pathway for repairing DSBs, are linked to breast cancer susceptibility, including BRCA2. Using reporter mice that express an inducible endonuclease, we find that HDR is particularly robust in mammary tissue during puberty and pregnancy, accounting for 34–40% of detected repair events, more than in other tissues examined. Brca2 hypomorphic mutation leads to HDR defects in mammary epithelium during puberty and pregnancy, including in different epithelial lineages. Notably, a similar dependence on Brca2 is observed in other proliferative tissues, including small intestine epithelium. Our results suggest that the greater reliance on HDR in the proliferating mammary gland, rather than a specific dependence on BRCA2, may increase its susceptibility to tumorigenesis incurred by BRCA2 mutation.
PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation
Authors: Xie Min , Yu Yan , Kang Rui , Zhu Shan , Yang Liangchun , Zeng Ling , Sun Xiaofang , Yang Minghua , Billiar Timothy R. , Wang Haichao , Cao Lizhi , Jiang Jianxin , Tang Daolin
Published: October 2016

Sepsis, severe sepsis and septic shock are the main cause of mortality in non-cardiac intensive care units. Immunometabolism has been linked to sepsis; however, the precise mechanism by which metabolic reprogramming regulates the inflammatory response is unclear. Here we show that aerobic glycolysis contributes to sepsis by modulating inflammasome activation in macrophages. PKM2-mediated glycolysis promotes inflammasome activation by modulating EIF2AK2 phosphorylation in macrophages. Pharmacological and genetic inhibition of PKM2 or EIF2AK2 attenuates NLRP3 and AIM2 inflammasomes activation, and consequently suppresses the release of IL-1β, IL-18 and HMGB1 by macrophages. Pharmacological inhibition of the PKM2–EIF2AK2 pathway protects mice from lethal endotoxemia and polymicrobial sepsis. Moreover, conditional knockout of PKM2 in myeloid cells protects mice from septic death induced by NLRP3 and AIM2 inflammasome activation. These findings define an important role of PKM2 in immunometabolism and guide future development of therapeutic strategies to treat sepsis.
Form, shape and function: segmented blood flow in the choriocapillaris
Authors: Zouache M. A. , Eames I. , Klettner C. A. , Luthert P. J.
Published: October 2016

The development of fluid transport systems was a key event in the evolution of animals and plants. While within vertebrates branched geometries predominate, the choriocapillaris, which is the microvascular bed that is responsible for the maintenance of the outer retina, has evolved a planar topology. Here we examine the flow and mass transfer properties associated with this unusual geometry. We show that as a result of the form of the choriocapillaris, the blood flow is decomposed into a tessellation of functional vascular segments of various shapes delineated by separation surfaces across which there is no flow, and in the vicinity of which the transport of passive substances is diffusion-limited. The shape of each functional segment is determined by the distribution of arterioles and venules and their respective relative flow rates. We also show that, remarkably, the mass exchange with the outer retina is a function of the shape of each functional segment. In addition to introducing a novel framework in which the structure and function of the metabolite delivery system to the outer retina may be investigated in health and disease, the present work provides a general characterisation of the flow and transfers in multipole Hele-Shaw configurations.
Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan
Authors: Chang Sui-Yuan , Lin Pi-Han , Cheng Chien-Lin , Chen Mao-Yuan , Sun Hsin-Yun , Hsieh Szu-Min , Sheng Wang-Huei , Su Yi-Ching , Su Li-Hsin , Chang Shu-Fang , Liu Wen-Chun , Hung Chien-Ching , Chang Shan-Chwen
Published: October 2016

Antiretroviral therapy containing an integrase strand transfer inhibitor (INSTI) plus two NRTIs has become the recommended treatment for antiretroviral-naive HIV-1-infected patients in the updated guidelines. We aimed to determine the prevalence of INSTI-related mutations in Taiwan. Genotypic resistance assays were performed on plasma from ARV-naïve patients (N = 948), ARV-experienced but INSTI-naive patients (N = 359), and raltegravir-experienced patients (N = 63) from 2006 to 2015. Major INSTI mutations were defined according to the IAS-USA list and other substitutions with a Stanford HIVdb score ≧ 10 to at least one INSTI were defined as minor mutations. Of 1307 HIV-1 samples from patients never exposed to INSTIs, the overall prevalence of major resistance mutations to INSTIs was 0.9% (n = 12), with an increase to 1.2% in 2013. Of these 12 sequences, 11 harboured Q148H/K/R, one Y143R, and none N155H. Of 30 sequences (47.6%) with INSTI-resistant mutations from raltegravir-experienced patients, 17 harboured Q148H/K/R, 8 N155H, and 6 Y143C/R. Other than these major mutations, the prevalence of minor mutations were 5.3% and 38.1%, respectively, in ARV-naive and raltegravir-experienced patients. The overall prevalence of INSTI mutations remains low in Taiwan. Surveillance of INSTI resistance is warranted due to circulation of polymorphisms contributing to INSTI resistance and expected increasing use of INSTIs.
Single 5 μm diameter needle electrode block modules for unit recordings in vivo
Authors: Sawahata H. , Yamagiwa S. , Moriya A. , Dong T. , Oi H. , Ando Y. , Numano R. , Ishida M. , Koida K. , Kawano T.
Published: October 2016

Investigations into mechanisms in various cortical areas can be greatly improved and supported by stable recording of single neuronal activity. In this study, fine silicon wire electrodes (diameter 3 μm, length 160 μm) are fabricated by vapor–liquid–solid (VLS) growth with the aim of stabilizing recording and reducing the invasiveness on the measurement procedure. The electrode is fabricated on a modular 1 ×  1 mm2 conductive silicon block that can be assembled into a number of different device packages, for example on rigid or flexible printed circuit boards (PCB). After plating with a 5 μm diameter platinum black, the needle exhibits an electrical impedance of ~100 kΩ at 1 kHz in saline. The in vivo recording capability of the device is demonstrated using mice, and spike signals with peak-to-peak amplitudes of 200−300 μV in the range 0.5−3 kHz are stably detected, including single-unit activities in cortical layer 2/3. In addition, the device packaged with a flexible PCB shows stable unit recordings for 98.5 min (n = 4). Consequently, our modular, low-invasive needle electrode block devices present an effective route for single-unit recordings in vivo, as well as demonstrating adaptability in device design for a diverse range of experiments.
MiR1918 enhances tomato sensitivity to Phytophthora infestans infection
Authors: Luan Yushi , Cui Jun , Wang Weichen , Meng Jun
Published: October 2016

Late blight of tomato is caused by the oomycete pathogen Phytophthora infestans. In our previous work, we identified and characterized a miR1918 in P. infestans (pi-miR1918), and showed that its sequence is similar to the sequence of tomato miR1918 (sly-miR1918). In this study, we used Arabidopsis thaliana pre-miR159a as a backbone to synthesize pi-miR1918 via PCR and mutagenesis. The artificial pi-miR1918 was used to investigate the role of miR1918 in tomato-P. infestans interaction. Trangenic tomato plants that overexpressed the artificial pi-miR1918 displayed more serious disease symptoms than wild-type tomato plants after infection with P. infestans, as shown by increased number of necrotic cells, lesion sizes and number of sporangia per leaf. The target genes of pi-miR1918 and sly-miR1918 were also predicted for tomato and P. infestans, respectively. qPCR analysis of these targets also performed during tomato-P. infestans interaction. The expression of target gene, RING finger were negatively correlated with miR1918 in the all Lines of transgenic tomato plants. In addition, we used the 5′ RACE to determine the cleavage site of miR1918 to RING finger. These results suggested that miR1918 might be involved in the silencing of target genes, thereby enhancing the susceptibility of tomato to P. infestans infection.
Equatorial Pacific forcing of western Amazonian precipitation during Heinrich Stadial 1
Authors: Zhang Yancheng , Zhang Xu , Chiessi Cristiano M. , Mulitza Stefan , Zhang Xiao , Lohmann Gerrit , Prange Matthias , Behling Hermann , Zabel Matthias , Govin Aline , Sawakuchi André O. , Cruz Francisco W. , Wefer Gerold
Published: October 2016

Abundant hydroclimatic evidence from western Amazonia and the adjacent Andes documents wet conditions during Heinrich Stadial 1 (HS1, 18–15 ka), a cold period in the high latitudes of the North Atlantic. This precipitation anomaly was attributed to a strengthening of the South American summer monsoon due to a change in the Atlantic interhemispheric sea surface temperature (SST) gradient. However, the physical viability of this mechanism has never been rigorously tested. We address this issue by combining a thorough compilation of tropical South American paleorecords and a set of atmosphere model sensitivity experiments. Our results show that the Atlantic SST variations alone, although leading to dry conditions in northern South America and wet conditions in northeastern Brazil, cannot produce increased precipitation over western Amazonia and the adjacent Andes during HS1. Instead, an eastern equatorial Pacific SST increase (i.e., 0.5–1.5 °C), in response to the slowdown of the Atlantic Meridional Overturning Circulation during HS1, is crucial to generate the wet conditions in these regions. The mechanism works via anomalous low sea level pressure over the eastern equatorial Pacific, which promotes a regional easterly low-level wind anomaly and moisture recycling from central Amazonia towards the Andes.
Quantitative Relationship between Cadmium Uptake and the Kinetics of Phytochelatin Induction by Cadmium in a Marine Diatom
Authors: Wu Yun , Guo Zhiqiang , Zhang Wei , Tan Qiaoguo , Zhang Li , Ge Xinlei , Chen Mindong
Published: October 2016

Heavy metals activate the synthesis of phytochelatins (PCs), while the induced PCs might affect metal uptake via chelating intracellular free metals. However, the relationship of PCs to metal uptake is poorly understood. In this study, we examined the kinetics of cadmium (Cd) accumulation and the synthesis of PCs in a marine diatom, Thalassiosira weissflogii, under different irradiance levels. Irradiance alone could not change the concentrations of PCs in the Cd-free treatments, while higher irradiance accelerated the induction of intracellular PCs at the same [Cd2+] level. PC-SH (2 × PC2 + 3 × PC3 + 4 × PC4) was bound with Cd at a stoichiometric ratio of 2 to 49 in our short-term uptake experiments, indicating that PC induction is sufficient to serve as the first line of defense against Cd stress. A positive linear correlation between the induction rate of PCs and the Cd uptake rate was observed, while the ratio of the PC content to intracellular Cd varied greatly when the irradiance was increased several fold. Because metal uptake has been successfully used in predicting acute metal toxicity, our findings are helpful for understanding the role of PCs in metal detoxification and developing PCs as biomarkers for metal sensitivity.
ADAMTS-10 and -6 differentially regulate cell-cell junctions and focal adhesions
Authors: Cain Stuart A. , Mularczyk Ewa J. , Singh Mukti , Massam-Wu Teresa , Kielty Cay M.
Published: October 2016

ADAMTS10 and ADAMTS6 are homologous metalloproteinases with ill-defined roles. ADAMTS10 mutations cause Weill-Marchesani syndrome (WMS), implicating it in fibrillin microfibril biology since some fibrillin-1 mutations also cause WMS. However little is known about ADAMTS6 function. ADAMTS10 is resistant to furin cleavage, however we show that ADAMTS6 is effectively processed and active. Using siRNA, over-expression and mutagenesis, it was found ADAMTS6 inhibits and ADAMTS10 is required for focal adhesions, epithelial cell-cell junction formation, and microfibril deposition. Either knockdown of ADAMTS6, or disruption of its furin processing or catalytic sites restores focal adhesions, implicating its enzyme activity acts on targets in the focal adhesion complex. In ADAMTS10-depleted cultures, expression of syndecan-4 rescues focal adhesions and cell-cell junctions. Recombinant C-termini of ADAMTS10 and ADAMTS6, both of which induce focal adhesions, bind heparin and syndecan-4. However, cells overexpressing full-length ADAMTS6 lack heparan sulphate and focal adhesions, whilst depletion of ADAMTS6 induces a prominent glycocalyx. Thus ADAMTS10 and ADAMTS6 oppositely affect heparan sulphate-rich interfaces including focal adhesions. We previously showed that microfibril deposition requires fibronectin-induced focal adhesions, and cell-cell junctions in epithelial cultures. Here we reveal that ADAMTS6 causes a reduction in heparan sulphate-rich interfaces, and its expression is regulated by ADAMTS10.
Specificity Evaluation and Disease Monitoring in Arthritis Imaging with Complement Receptor of the Ig superfamily targeting Nanobodies
Authors: Zheng Fang , Perlman Harris , Matthys Patrick , Wen Yurong , Lahoutte Tony , Muyldermans Serge , Lu Shemin , De Baetselier Patrick , Schoonooghe Steve , Devoogdt Nick , Raes Geert
Published: October 2016

Single-photon emission computed tomography combined with micro-CT (SPECT/μCT) imaging using Nanobodies against complement receptor of the Ig superfamily (CRIg), found on tissue macrophages such as synovial macrophages, has promising potential to visualize joint inflammation in experimental arthritis. Here, we further addressed the specificity and assessed the potential for arthritis monitoring. Signals obtained with 99mTc-labelled NbV4m119 Nanobody were compared in joints of wild type (WT) versus CRIg−/− mice with collagen-induced arthritis (CIA) or K/BxN serum transfer-induced arthritis (STIA). In addition, SPECT/μCT imaging was used to investigate arthritis development in STIA and in CIA under dexamethasone treatment. 99mTc-NbV4m119 accumulated in inflamed joints of WT, but not CRIg−/− mice with CIA and STIA. Development and spontaneous recovery of symptoms in STIA was reflected in initially increased and subsequently reduced joint accumulation of 99mTc-NbV4m119. Dexamethasone treatment of CIA mice reduced 99mTc-NbV4m119 accumulation as compared to saline control in most joints except knees. SPECT/μCT imaging with 99mTc-NbV4m119 allows specific assessment of inflammation in different arthritis models and provides complementary information to clinical scoring for quantitatively and non-invasively monitoring the pathological process and the efficacy of arthritis treatment.
Chitosan Hydrogel Structure Modulated by Metal Ions
Authors: Nie Jingyi , Wang Zhengke , Hu Qiaoling
Published: October 2016

As one of the most important polysaccharide, chitosan (CS) has generated a great deal of interest for its desirable properties and wide applications. In the utilization of CS materials, hydrogel is a major and vital branch. CS has the ability to coordinate with many metal ions by a chelation mechanism. While most researchers focused on the applications of complexes between CS and metal ions, the complexes can also influence gelation process and structure of CS hydrogel. In the present work, such influence was studied with different metal ions, revealing two different kinds of mechanisms. Strong affinity between CS and metal ions leads to structural transition from orientation to multi-layers, while weak affinity leads to composite gel with in-situ formed inorganic particles. The study gave a better understanding of the gelation mechanism and provided strategies for the modulation of hydrogel morphology, which benefited the design of new CS-based materials with hierarchical structure and facilitated the utilization of polysaccharide resources.
LMO2 attenuates tumor growth by targeting the Wnt signaling pathway in breast and colorectal cancer
Authors: Liu Ye , Huang Di , Wang Zhaoyang , Wu Chao , Zhang Zhao , Wang Dan , Li Zongjin , Zhu Tianhui , Yang Shuang , Sun Wei
Published: October 2016

The proto-oncogene LIM-domain only 2 (lmo2) was traditionally considered to be a pivotal transcriptional regulator in hematopoiesis and leukemia. Recently, the cytosolic localization of LMO2 was revealed in multiple epithelial tissues and a variety of solid tumors. However, the function of LMO2 in these epithelia and solid tumors remains largely unclear. The Wnt signaling pathway is a crucial determinant of development, and abnormalities in several key segments of this pathway contribute to oncogenesis. The current study demonstrated that LMO2 participates in the regulation of canonical Wnt signaling in the cytoplasm by binding to Dishevelled-1/2 (DVL-1/2) proteins. These interactions occurred at the PDZ domain of Dishevelled, and LMO2 subsequently attenuated the activation of the key factor β-catenin in the canonical Wnt signaling pathway. Meanwhile, significantly decreased expression of LMO2 was detected in breast and colorectal cancers, and the downregulation of LMO2 in these cells increased cell proliferation and reduced apoptosis. Taken together, the data in this study revealed a novel crosstalk between LMO2 and the Wnt signaling pathway during tumorigenesis and suggested that LMO2 might be a tumor suppressor in certain solid tumors, in contrast to its traditional oncogenic role in the hematopoietic system.
Flaw-induced plastic-flow dynamics in bulk metallic glasses under tension
Authors: Chen S. H. , Yue T. M. , Tsui C. P. , Chan K. C.
Published: October 2016

Inheriting amorphous atomic structures without crystalline lattices, bulk metallic glasses (BMGs) are known to have superior mechanical properties, such as high strength approaching the ideal value, but are susceptible to catastrophic failures. Understanding the plastic-flow dynamics of BMGs is important for achieving stable plastic flow in order to avoid catastrophic failures, especially under tension, where almost all BMGs demonstrate limited plastic flow with catastrophic failure. Previous findings have shown that the plastic flow of BMGs displays critical dynamics under compression tests, however, the plastic-flow dynamics under tension are still unknown. Here we report that power-law critical dynamics can also be achieved in the plastic flow of tensile BMGs by introducing flaws. Differing from the plastic flow under compression, the flaw-induced plastic flow under tension shows an upward trend in the amplitudes of the load drops with time, resulting in a stable plastic-flow stage with a power-law distribution of the load drop. We found that the flaw-induced plastic flow resulted from the stress gradients around the notch roots, and the stable plastic-flow stage increased with the increase of the stress concentration factor ahead of the notch root. The findings are potentially useful for predicting and avoiding the catastrophic failures in tensile BMGs by tailoring the complex stress fields in practical structural-applications.
Modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines
Authors: Frye R E , Rose S , Chacko J , Wynne R , Bennuri S C , Slattery J C , Tippett M , Delhey L , Melnyk S , Kahler S G , MacFabe D F
Published: October 2016

Propionic acid (PPA) is a ubiquitous short-chain fatty acid, which is a major fermentation product of the enteric microbiome. PPA is a normal intermediate of metabolism and is found in foods, either naturally or as a preservative. PPA and its derivatives have been implicated in both health and disease. Whereas PPA is an energy substrate and has many proposed beneficial effects, it is also associated with human disorders involving mitochondrial dysfunction, including propionic acidemia and autism spectrum disorders (ASDs). We aimed to investigate the dichotomy between the health and disease effects of PPA by measuring mitochondrial function in ASD and age- and gender-matched control lymphoblastoid cell lines (LCLs) following incubation with PPA at several concentrations and durations both with and without an in vitro increase in reactive oxygen species (ROS). Mitochondrial function was optimally increased at particular exposure durations and concentrations of PPA with ASD LCLs, demonstrating a greater enhancement. In contrast, increasing ROS negated the positive PPA effect with the ASD LCLs, showing a greater detriment. These data demonstrate that enteric microbiome metabolites such as PPA can have both beneficial and toxic effects on mitochondrial function, depending on concentration, exposure duration and microenvironment redox state with these effects amplified in LCLs derived from individuals with ASD. As PPA, as well as enteric bacteria, which produce PPA, have been implicated in a wide variety of diseases, including ASD, diabetes, obesity and inflammatory diseases, insight into this metabolic modulator from the host microbiome may have wide applications for both health and disease.
A support vector machine model provides an accurate transcript-level-based diagnostic for major depressive disorder
Authors: Yu J S , Xue A Y , Redei E E , Bagheri N
Published: October 2016

Major depressive disorder (MDD) is a critical cause of morbidity and disability with an economic cost of hundreds of billions of dollars each year, necessitating more effective treatment strategies and novel approaches to translational research. A notable barrier in addressing this public health threat involves reliable identification of the disorder, as many affected individuals remain undiagnosed or misdiagnosed. An objective blood-based diagnostic test using transcript levels of a panel of markers would provide an invaluable tool for MDD as the infrastructure—including equipment, trained personnel, billing, and governmental approval—for similar tests is well established in clinics worldwide. Here we present a supervised classification model utilizing support vector machines (SVMs) for the analysis of transcriptomic data readily obtained from a peripheral blood specimen. The model was trained on data from subjects with MDD (n=32) and age- and gender-matched controls (n=32). This SVM model provides a cross-validated sensitivity and specificity of 90.6% for the diagnosis of MDD using a panel of 10 transcripts. We applied a logistic equation on the SVM model and quantified a likelihood of depression score. This score gives the probability of a MDD diagnosis and allows the tuning of specificity and sensitivity for individual patients to bring personalized medicine closer in psychiatry.
Facile synthesis of Ni(OH)2nanoplates on nitrogen-doped carbon foam for nonenzymatic glucose sensors
Authors: Guo Qiaohui , Zhang Man , Liu Shuwu , Zhou Gangyong , Li Xia , Hou Haoqing , Wang Li
Published: October 2016

Ni(OH)2nanoplates are uniformly anchored on nitrogen-doped carbon foam, resulting in 3D hierarchical architectures with application in nonenzymatic glucose biosensing.
Simultaneous determination of nitroimidazoles and amphenicol antibiotics in water samples using ultrasound-assisted dispersive liquid–liquid microextraction coupled with ultra-high-performance liquid chromatography with tandem mass spectrometry
Authors: Ma Shuping , Ye Xiu , Huang Peiting , Zhao Longshan , Liang Ning
Published: October 2016

A method involving UA-DLLME coupled with UHPLC-MS/MS was developed for the determination of four antibiotics in water samples.
Solvent-dependent copper-catalyzed synthesis of pyrazoles under aerobic conditions
Authors: Pünner Florian , Sohtome Yoshihiro , Sodeoka Mikiko
Published: October 2016

We have developed a copper-catalyzed oxidative cyclization of hydrazones under aerobic conditions, enabling solvent-dependent selective synthesis of different pyrazoles.
A new five-coordinated copper compound for efficient degradation of methyl orange and Congo red in the absence of UV–visible radiation
Authors: Han Li-Juan , Kong Ya-Jie , Yan Ting-Jiang , Fan Lu-Tong , Zhang Qi , Zhao Hua-Jun , Zheng He-Gen
Published: October 2016

A five-coordinated compound, Cu2(2,2-bipy)2(pfbz)4, displays excellent properties of degrading methyl orange and Congo red in the absence of UV–visible radiation.
Lanthanide-activated scheelite nanocrystal phosphors prepared by the low-temperature vapor diffusion sol–gel method
Authors: Culver Sean P. , Brutchey Richard L.
Published: October 2016

The high degree of synthetic flexibility inherent to the vapor diffusion sol–gel method has enabled the synthesis of a CaWO4:(Eu,Tb) dual-sensitized white light emitting nanocrystal phosphor.
Solvent-induced structural diversity in tetranuclear Ni(ii) Schiff-base complexes: the first Ni4single-molecule magnet with a defective dicubane-like topology
Authors: Herchel Radovan , Nemec Ivan , Machata Marek , Trávníček Zdeněk
Published: October 2016

The tetranuclear NiIIcomplexes with the Ni4O4cubane-like core (1) and the Ni4O6defective dicubane core (2) were studied, and the latter identified as a first single-molecule magnet with such topology.