bluuebunny/crossref_metadata_2025 huggingface dataset:
Uncertainties in coupled regional Arctic climate simulations associated with the used land surface model
Authors: Matthes Heidrun , Rinke Annette , Zhou Xu , Dethloff Klaus
Published: July 2017

Permafrost is one of the most important components of Arctic land. Regional atmosphere‐snow‐permafrost interactions can be best studied with Regional Climate Models (RCMs) due to their higher horizontal resolution compared to global climate models. The development of Arctic RCMs with sophisticated land models is therefore very important. Comparing RCMs with different land surface model (LSM) components then allows the quantification of the uncertainties associated with the LSM. This study analyzes two simulations of coupled atmosphere‐land RCMs over the Arctic, which differ only in their land component, while the atmospheric model component is the same. Specifically, we examine HIRHAM5‐CLM4 (HIRHAM5 coupled with the sophisticated land model CLM4) and HIRHAM5 (HIRHAM5 coupled with the simpler land model of ECHAM5). We discuss the two models' abilities to represent observations on permafrost‐like permafrost extent, active layer thickness (ALT), and soil temperature profiles, as well as on the representation of the Arctic atmosphere, based on simulations over 1979–2014. In comparison to HIRHAM5, HIRHAM5‐CLM4 significantly reduces the simulated bias in ALT and winter soil temperatures. We find that the simulation of soil temperature and subsequently ALT is sensitive to soil thermal and hydraulic parameter representation in the models. The simulation of permafrost extent is sensitive to the initial soil temperature state in the models. Both HIRHAM5 and HIRHAM5‐CLM4 do similarly well in modeling the Arctic 2 m air temperature and atmospheric circulation. Changing the land model impacts the 2 m air temperature significantly over land and the atmospheric circulation predominantly over the Arctic Ocean, associated with changes in baroclinic cyclones.
Epsilon iron oxide: Origin of the high coercivity stable low Curie temperature magnetic phase found in heated archeological materials
Authors: López‐Sánchez J. , McIntosh G. , Osete M. L. , del Campo A. , Villalaín J. J. , Pérez L. , Kovacheva M. , Rodríguez de la Fuente O.
Published: July 2017

The identification of epsilon iron oxide (ɛ‐Fe2O3) as the low Curie temperature high coercivity stable phase (HCSLT) carrying the remanence in heated archeological samples has been achieved in samples from two archeological sites that exhibited the clearest evidence of the presence of the HCSLT. This uncommon iron oxide has been detected by Confocal Raman Spectroscopy (CRS) and characterized by rock magnetic measurements. Large numbers of ɛ‐Fe2O3 microaggregates (in CO) or isolated clusters (in HEL) could be recognized, distributed over the whole sample, and embedded within the ceramic matrix, along with hematite and pseudobrookite and with minor amounts of anatase, rutile, and maghemite. Curie temperature estimates of around 170°C for CO and 190°C for HEL are lower than for pure, synthetic ɛ‐Fe2O3 (227°C). This, together with structural differences between the Raman spectra of the archeologically derived and synthetic samples, is likely due to Ti substitution in the ɛ‐Fe2O3 crystal lattice. The γ‐Fe2O3‐ɛ‐Fe2O3‐α‐Fe2O3 transformation series has been recognized in heated archeological samples, which may have implications in terms of their thermal history and in the factors that govern the formation of ɛ‐Fe2O3.
Contributions of radiative factors to enhanced dryland warming over East Asia
Authors: Zhang Yanting , Guan Xiaodan , Yu Haipeng , Xie Yongkun , Jin Hongchun
Published: July 2017

Enhanced near‐surface atmospheric warming has occurred over East Asia in recent decades, especially in drylands. Although local factors have been confirmed to provide considerable contributions to this warming, such factors have not been sufficiently analyzed. In this study, we extracted the radiatively forced temperature (RFT) associated with the built‐up greenhouse gases, aerosol emission, and various other radiative forcing over East Asia and found a close relationship between RFT and CO2. In addition, using climate model experiments, we explored the responses of temperature changes to black carbon (BC), CO2, and SO4 and found that the enhanced dryland warming induced by CO2 had the largest magnitude and was strengthened by the warming effect of BC. Moreover, the sensitivity of daily maximum and minimum temperature changes to BC, CO2, and SO4 was examined. It showed asymmetric responses of daily maximum and minimum temperature to radiative factors, which led to an obvious change of diurnal temperature range (DTR), especially in drylands. The DTR's response to CO2 is the most significant. Therefore, CO2 not only plays a dominant role in enhanced warming but also greatly affects the decrease of DTR in drylands. However, the mechanisms of these radiative factors' effects in the process of DTR change are not clear and require more investigation.
Escapees from Rhombomeric Lineage Restriction: Extensive Migration Rostral to the r4/r5 Border of Hox‐a3 Expression
Authors: Watson Charles , Leanage Gayeshika , Makki Nadja , Tvrdik Petr
Published: July 2017

The rhombomeric compartments of the hindbrain are characterized by lineage restriction; cells born in one compartment generally remain there and do not migrate to neighboring rhombomeres. Two well‐known exceptions are the substantial migrations of the pontine nuclei and the mammalian facial nucleus. In this study we used Hoxa3‐Cre lineage to permanently mark cells that originate in rhombomeres caudal to r4. We found that cells born caudal to the r4/r5 border migrate forwards to a number of different locations in rhombomeres 1–4; the final locations include the interfascicular trigeminal nucleus, the principal trigeminal nucleus, the pontine nuclei, the reticulotegmental nucleus, the ventral nucleus of the lateral lemniscus, and the lateral and medial vestibular nuclei. We suggest that there are numerous exceptions to the principle of rhombomeric lineage restriction that have previously gone unnoticed. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:1838–1846, 2017. © 2017 Wiley Periodicals, Inc.
Preparation of an Aluminum and Iron‐Based Coagulant From Fly Ash for Industrial Wastewater Treatment
Authors: Hu Kai , Zhao Qing‐Liang , Chen Wei , Tang Feng
Published: July 2017

Fly ash was investigated to produce a composite coagulant containing aluminum (Al) and iron (Fe) salts through the calcination and leaching processes. The extraction of Al and Fe oxides from fly ash demonstrated similar results for HCl and H2SO4 leaching. Besides, the calcination pretreatment of fly ash (without any additive) was found to be less effective in extraction. However, the conversion efficiencies of Al and Fe were affected greatly by calcination pretreatment with addition of Na2CO3, and leaching conditions of ratio of solution to fly ash (L/S) and H+ concentration. The maximum concentrations of Al and Fe solubilized from fly ash were 0.21 and 0.04 mol/L, respectively, which were attained by calcination pretreatment using an optimal mass ratio (ca. 1:16.7) of Na2CO3 to fly ash at 805°C. These concentrations correspond to conversion efficiencies of 31.2% for Fe and 18.3% for Al in the fly ash. The slurry was filtrated to obtain a solution containing Al‐ and Fe‐sulfates and silicates. The Al/Fe/Si mole ratio indicated the feasibility of further production of inorganic polymer coagulant. The produced coagulant was determined to be effective for treating soybean wastewater and dairy wastewater in terms of COD and SS removal.
In vitro and in vivo gene delivery using chitosan/hyaluronic acid nanoparticles: Influences of molecular mass of hyaluronic acid and lyophilization on transfection efficiency
Authors: Sato Toshinori , Nakata Mitsuhiro , Yang Zhihong , Torizuka Yu , Kishimoto Satoko , Ishihara Masayuki
Published: July 2017

Background

Lyophilization is an effective method for preserving nonviral gene vectors. To improve the stability and transgene expression of lyophilized plasmid DNA (pDNA) complexes, we coated the surfaces of pDNA/chitosan complexes with hyaluronic acid (HA) of varying molecular masses. The transgene expression of pDNA/chitosan/HA ternary complexes was characterized in vitro and in vivo.

Methods

pDNA complexes were lyophilized overnight and the resultant products with spongy, porous consistencies were stored at −30, 4 or 25°C for 2 weeks. Rehydrated complexes were characterized using gel retardation assays, aiming to confirm complex formation, measure particle size and evaluate zeta potential, as well as conduct luciferase gene reporter assays. The anti‐tumor effects of pDNA ternary complexes were evaluated using suicide gene (pTK) coding thymidine kinase in Huh7‐implanted mice.

Results

Transfection efficiencies of pDNA/chitosan/HA ternary complexes were dependent on the average molecular masses of HA. The coating of pDNA/chitosan complexes with HA maintained the cellular transfection efficiencies of lyophilized pDNA ternary complexes. Furthermore, intratumoral injection of lyophilized, rehydrated pDNA ternary complexes into tumor‐bearing mice showed a significant suppression of tumor growth.

Conclusions

The coating of pDNA/chitosan complexes with high‐molecular‐weight HA augmented the stability and cellular transfection ability of the complexes after lyophilization‐rehydration.
A Novel Bola‐Type Rosin‐Based Functional Surfactant and Its Synergistic Effect with Natural Surfactant Saponin
Authors: Lin Hai‐xia , Yang Ming‐sheng , Li Juan , Chen Xiao‐yu , Jiang Jian‐xin , Han Chun‐rui
Published: July 2017

A novel bola‐type acrylic‐modified rosin ester tertiary ammonium salt surfactant (AETAS) with two hydrophilic groups and a rigid hydrophobic group was synthesized through a simple method from rosin acid, which is a natural raw material. The chemical structure of the synthesized surfactant was confirmed by infrared spectroscopy and nuclear magnetic resonance spectroscopy (1H NMR and 13C NMR). The critical micelle concentration (CMC) of the AETAS was 0.44 g/L, and the surface tension at the CMC (γcmc) was 45.02 mN/m. Self‐assembly behavior of the AETAS in aqueous solution was characterized by transmission electron microscopy. The micelle diameter of the AETAS was about 150 nm in aqueous solution. We also explored the synergy of the AETAS and soapnut saponin. The binary surfactant compound systems of the AETAS and soapnut saponin had obvious synergistic effect in enhancing surface activity when the mass ratio of AETAS/soapnut saponin was 1:1. The γcmc of soapnut saponin was 47.70 mN/m when the concentration reached 0.46 g/L, but the γcmc of mixtures decreased to 44.26 mN/m at 0.30 g/L. The emulsification ability of the mixtures was significantly improved and the emulsion performance increased from 245 to 595 s when the mass ratio of AETAS/soapnut saponin was 1:1.
“Ice Axe Wrist”: A Case Report of Intersection Syndrome in 2 Climbers
Authors: Tobin Anna L.
Published: July 2017

Intersection syndrome is an inflammatory condition located at the crossing point between the first and second dorsal compartments in the wrist. It is an uncommon presentation but has been recognized as an injury typical of rowers (when it is named oarsman’s wrist) and other sports such as racquet sports, baseball, cycling, hockey, golf, ice hockey, skiing, and softball. It has not been previously described in climbers. This report details 2 cases of intersection associated with the use of an ice axe. The first presentation was in a female climber who was using an ice axe for climbing in the Nepal Himalayas and the second was in a male climber using an ice axe for winter climbing training in the Alps. Both climbers presented with wrist pain, swelling, and crepitus over the dorsum of the wrist, about 5 cm proximal to Lister’s tubercle. Although well documented in other sporting populations, there seems to be limited reporting of intersection syndrome in the climbing population. It may be worth considering a diagnosis of “ice axe wrist” as a differential in patients who have been using ice axes in climbing or mountaineering.
Translational science in chronic kidney disease
Authors: Sanchez-Niño Maria Dolores , Sanz Ana B. , Ramos Adrian M. , Ruiz-Ortega Marta , Ortiz Alberto
Published: July 2017

The KDIGO definition of chronic kidney disease (CKD) allowed a more detailed characterization of CKD causes, epidemiology and consequences. The picture that has emerged is worrisome from the point of view of translation. CKD was among the fastest growing causes of death in the past 20 years in age-adjusted terms. The gap between recent advances and the growing worldwide mortality appears to result from sequential roadblocks that limit the flow from basic research to clinical development (translational research type 1, T1), from clinical development to clinical practice (translational research T2) and result in deficient widespread worldwide implementation of already available medical advances (translational research T3). We now review recent advances and novel concepts that have the potential to change the practice of nephrology in order to improve the outcomes of the maximal number of individuals in the shortest possible interval. These include: (i) updating the CKD concept, shifting the emphasis to the identification, risk stratification and care of early CKD and redefining the concept of aging-associated ‘physiological’ decline of renal function; (ii) advances in the characterization of aetiological factors, including challenging the concept of hypertensive nephropathy, the better definition of the genetic contribution to CKD progression, assessing the role of the liquid biopsy in aetiological diagnosis and characterizing the role of drugs that may be applied to the earliest stages of injury, such as SGLT2 inhibitors in diabetic kidney disease (DKD); (iii) embracing the complexity of CKD as a network disease and (iv) exploring ways to optimize implementation of existing knowledge.
Clinical Science: showcasing the breadth of the journal
Authors: Cooper Mark E. , Touyz Rhian M.
Published: July 2017

This Editorial introduces the review articles published in this issue to showcase the range of subject areas, such as neurology, the respiratory system, kidney disease and oxidative stress, covered by Clinical Science.
Ferromagnetism found in two-dimensional materials
Authors: Miller Johanna L.
Published: July 2017

Whether long-range magnetic order could survive in the 2D limit was an open and fundamental question. The answer is that it can, but it has some surprises in store.
Quantum computing with neutral atoms
Authors: Weiss David S. , Saffman Mark
Published: July 2017

With their hyperfine states serving as two-level qubits, atoms can be packed into closely spaced, laser-cooled arrays and be individually addressed using laser pulses.
Sequential interactions with Mre11-Rad50-Nbs1 activate ATM/Tel1 at DNA double-strand breaks and telomeres
Authors: Limbo Oliver , Yamada Yoshiki , Russell Paul
Published: July 2017

The Mre11-Rad50-Nbs1 (MRN) protein complex, CtIP/Ctp1/Sae2 and ATM/Tel1 kinase protect genome integrity through their functions in DNA double-strand break (DSB) repair, checkpoint signaling, and telomere maintenance. Nbs1 has a conserved C-terminal motif that binds ATM, but the full extent of ATM interactions with MRN are unknown. Here, we show that Tel1 overexpression inSchizosaccharomyces pomberestores Tel1 activity at DSBs and telomeres in the absence of Nbs1. This activity requires Mre11, indicating that Tel1 overexpression drives low affinity binding to the Mre11-Rad50 subcomplex. Mre11-Rad50 binds DSBs innbs1Δ cells, and fusing the Tel1-binding motif of Nbs1 to Mre11 fully restores Tel1 signaling in these cells. Tel1 overexpression does not restore Tel1 signaling in cells carrying therad50-I1192Wmutation, which impairs the ability of Mre11-Rad50 to form the ATP-bound closed conformation. From these findings, we propose that Tel1 activation at DNA ends proceeds by a sequential mechanism initiated by high affinity binding to Nbs1 which recruits Tel1, followed by a low affinity interaction with Mre11-Rad50 in the closed conformation to activate Tel1.
Compressive Temporal Summation in Human Visual Cortex
Authors: Zhou Jingyang , Benson Noah C. , Kay Kendrick , Winawer Jonathan
Published: July 2017

Combining sensory inputs over space and time is fundamental to vision. Population receptive field models have been successful in characterizing spatial encoding throughout the human visual pathways. A parallel question—how visual areas in the human brain process information distributed over time—has received less attention. One challenge is that the most widely used neuroimaging method—fMRI—has coarse temporal resolution compared to the time-scale of neural dynamics. Here, via carefully controlled temporally modulated stimuli, we show that information about temporal processing can be readily derived from fMRI signal amplitudes in male and female subjects. We find that all visual areas exhibit sub-additive summation, whereby responses to longer stimuli are less than the linear prediction from briefer stimuli. We also find fMRI evidence that the neural response to two stimuli is reduced for brief interstimulus intervals (indicating adaptation). These effects are more pronounced in visual areas anterior to V1-V3. Finally, we develop a general model that shows how these effects can be captured with two simple operations: temporal summation followed by a compressive nonlinearity. This model operates for arbitrary temporal stimulation patterns and provides a simple and interpretable set of computations that can be used to characterize neural response properties across the visual hierarchy. Importantly, compressive temporal summation directly parallels earlier findings of compressive spatial summation in visual cortex describing responses to stimuli distributed across space. This indicates that for space and time, cortex uses a similar processing strategy to achieve higher-level and increasingly invariant representations of the visual world.

Significance statement

Combining sensory inputs over time is fundamental to seeing. Two important temporal phenomena aresummation, the accumulation of sensory inputs over time, andadaptation, a response reduction for repeated or sustained stimuli. We investigated these phenomena in the human visual system using fMRI. We built predictive models that operate on arbitrary temporal patterns of stimulation using two simple computations: temporal summation followed by a compressive nonlinearity. Our new temporal compressive summation model captures (1) subadditive temporal summation, and (2) adaptation. We show that the model accounts for systematic differences in these phenomena across visual areas. Finally, we show that for space and time, the visual system uses a similar strategy to achieve increasingly invariant representations of the visual world.
Analysis of behaviour in the Active Allothetic Place Avoidance task based on cluster analysis of the rat movement motifs
Authors: Gehring Tiago V. , Wesierska Malgorzata J. , Wójcik Daniel K. , Vasilaki Eleni
Published: July 2017

The Active Allothetic Place Avoidance test (AAPA) is a useful tool to study spatial memory in a dynamic world. In this task a rat, freely moving on a rotating circular arena, has to avoid a sector where shocks are presented. The standard analysis of memory performance in the AAPA task relies on evaluating individual performance measures. Here we present a new method of analysis for the AAPA test that focuses on the movement paths of the animals and utilizes a clustering algorithm to automatically extract the stereotypical types of behaviour as reflected in the recorded paths. We apply the method to experiments that study the effect of silver nanoparticles (AgNPs) on the reference memory and identify six major classes of movement motifs not previously described in AAPA tests. The method allows us to analyse the data with no prior expectations about the motion to be seen in the experiments.
Utilizing a resource of enrichment profiles in plasma for the systematic assessment of antibody selectivity
Authors: Fredolini Claudia , Byström Sanna , Sanchez-Rivera Laura , Ioannou Marina , Tamburro Davide , Branca Rui M. , Nilsson Peter , Lehtiö Janne , Schwenk Jochen M.
Published: July 2017

There is a strong need for procedures that enable context and application dependent validation of antibodies. Here we describe the foundation for a resource aiding more detailed assessment antibody selectivity for capturing endogenous proteins from human plasma. In 414 immunoprecipitation (IP) experiments with EDTA plasma, data was generated by mass spectrometry (LC-MS) with 157 antibodies (targeting 120 unique proteins). Out of a total of 1,313 unique proteins, 426 proteins (33%) were detected in > 20% of the assays and indicate a background comprised of mainly proteins from the complement system. For all proteins identified either in heat-treated or untreated EDTA plasma, frequencies of occurrence were derived. We determined z-scores for each IP as a measure of enrichment to annotate the antibodies into four categories (ON-target, CO-target, OFF-target and NO-target). For 45% (70/157) of the tested antibodies, the expected target proteins were enriched (z-score ≥3) above background. There were 84% (59/70) of binders that co-enriched other proteins beside the intended target, either due to OFF-target binding or predicted interactions. Comparing several antibodies raised against IGFBP2, the established library allowed us to describe protein complexes in plasma, and we employed multiplexed sandwich immunoassays to confirm these. In summary, the generated resource of plasma enrichment profiles and background proteins adds a very useful and yet lacking starting point for the assessment of antibody selectivity in this clinically important body fluid. The provided insights will contribute to a more informed use of validated affinity reagents and may lead to further advancements of plasma proteomics assays.
Identification of β-synuclein on secretory granules in chromaffin cells and the effects of α- and β-synuclein on BDNF discharge following fusion
Authors: Bittner Mary A. , Bohannon Kevin P. , Axelrod Daniel , Holz Ronald W.
Published: July 2017

Synuclein is strongly implicated in the pathogenesis of Parkinson’s disease as well as in other neurodegenerative diseases. However, its normal function in cells is not understood. The N-termini of α-, β-, and γ-synuclein are comprised of seven 11-amino acid repeats that are predicted to form amphipathic helices. α-Synuclein binds to negatively charged lipids, especially small vesicles and tubulates and vesiculates lipids. The membrane-binding and membrane-curving abilities raise the possibility that synuclein could alter cellular processes that involve highly curved structures. In the present study we examined the localization of endogenous synuclein in bovine chromaffin cells by immunocytochemistry and its possible function to control protein discharge upon fusion of the granule with the plasma membrane by regulating the fusion pore. We found with quantitative immunocytochemistry that endogenous β-synuclein associates with secretory granules. Endogenous α-synuclein only rarely is found on secretory granules. Overexpression of α-synuclein but not β-synuclein quickened the median duration of the post-fusion discharge of BDNF-pHluorin by 30%, consistent with α-synuclein speeding fusion pore expansion.
Evolutionary Action ofde novoMissense Variants across Pathways Prioritizes Genes Linked to Autism and Predicts Patient Phenotypic Severity
Authors: Koire Amanda , Buchovecky Christie , Katsonis Panagiotis , Kim Young Won , Wilson Stephen J. , Lichtarge Olivier
Published: July 2017

The pathogenicity of individualde novomissense mutations in autism spectrum disorder remains difficult to validate. Here we asked in 2,384 probands whether these variants exhibited collective functional impact biases across pathways. As measured with Evolutionary Action (EA) in 368 gene groupings, we found significant biases in axonogenesis, synaptic transmission, and other neurodevelopmental pathways. Strikingly, bothde novoand inherited missense variants in prioritized genes correlated with patient IQ. This general integrative approach thus detects missense variants most likely to contribute to autism pathogenesis and is the first, to our knowledge, to link missense variant impact to autism phenotypic severity.
Whole-exome sequencing identifies an α-globin cluster triplication resulting in increased clinical severity of β-thalassemia
Authors: Steinberg-Shemer Orna , Ulirsch Jacob C. , Noy-Lotan Sharon , Krasnov Tanya , Attias Dina , Dgany Orly , Laor Ruth , Sankaran Vijay G. , Tamary Hannah
Published: July 2017

Whole-exome sequencing (WES) has been increasingly useful for the diagnosis of patients with rare causes of anemia, particularly when there is an atypical clinical presentation or targeted genotyping approaches are inconclusive. Here, we describe a 20-yr-old man with a lifelong moderate-to-severe anemia with accompanying splenomegaly who lacked a definitive diagnosis. After a thorough clinical workup and targeted genetic sequencing, we identified a paternally inherited β-globin mutation (HBB:c.93-21G>A, IVS-I-110:G>A), a known cause of β-thalassemia minor. As this mutation alone was inconsistent with the severity of the anemia, we performed WES. Although we could not identify any relevant pathogenic single-nucleotide variants (SNVs) or small indels, copy-number variant (CNV) analyses revealed a likely triplication of the entire α-globin cluster, which was subsequently confirmed by multiplex ligation-dependent probe amplification. Treatment and follow-up was redefined according to the diagnosis of β-thalassemia intermedia resulting from a single β-thalassemia mutation in combination with an α-globin cluster triplication. Thus, we describe a case where the typical WES-based analysis of SNVs and small indels was unrevealing, but WES-based CNV analysis resulted in a definitive diagnosis that informed clinical decision-making. More generally, this case illustrates the value of performing CNV analysis when WES is otherwise unable to elucidate a clear genetic diagnosis.
Pollen limitation, reproductive success and flowering frequency in single‐flowered plants
Authors: Sun Hai‐Qin , Huang Bao‐Qiang , Yu Xiao‐Hong , Tian Chang‐Bao , Peng Qi‐Xuan , An De‐Jun
Published: July 2017

Flowering plants exhibit striking interspecific and intraspecific variation in flower number, which strongly influences the reproductive success of animal‐pollinated plants. However, the reproductive consequences of producing a single flower are poorly understood.

Here, we test if plants producing a single flower have a reproductive disadvantage compared with plants producing multiple flowers by combining field investigation of five deceptive orchids and a survey of published literature. Pollen limitation was estimated by comparing fruit production between hand pollination and open pollination. Flowering frequency was monitored over years to assess the potential advantage of producing a single flower.

Both single‐ and multiple‐flowered species suffered strong pollen limitation. However, single‐flowered species had significantly lower fruit set and produced fewer seeds per individual, although they had a significantly higher pollen removal than species with multiple flowers. A phylogenetically independent contrast of 28 species representing four of the five subfamilies of Orchidaceae revealed that fruit set was significantly positively associated with flower number. Both pollen removal and fruit set had a positive relationship with flower number within the multiple‐flowered species.

Synthesis. Current data and phylogenetically independent contrast support the hypothesis that producing a single flower has reproductive disadvantages. Single‐flowered species may compensate for low female success through high flowering frequency over years. This study provides insight into costs and benefits of producing a single flower in deceptive orchids.
Austerity Policies, the UK State and the Energy Utilities: a Changing Paradigm or Business as Usual?
Authors: de Carvalho Lucie
Published: July 2017

In 2008, the economic downturn coincided with a major shift in the energy sector paradigm. This state of emergency forced the UK government to try to steer the objectives of its major energy players. This crisis put the UK state's capacity to influence its mostly privately‐owned energy sector to the test. Using the example of energy utilities, this article aims to explore whether the austerity agenda impacted the relationship between the UK state and its public services. The purpose is to determine whether current multiple crises have forced the UK state to adopt an exceptionally interventionist approach that doesn't tally with the austerity agenda, or whether these crises merely revealed dynamics which had been underlying in the management of its energy utilities since the beginning of the neo‐liberal era.
Scrutinizing key steps for reliable metabarcoding of environmental samples
Authors: Alberdi Antton , Aizpurua Ostaizka , Gilbert M. Thomas P. , Bohmann Kristine
Published: July 2017

Metabarcoding of environmental samples has many challenges and limitations that require carefully considered laboratory and analysis workflows to ensure reliable results. We explore how decisions regarding study design, laboratory set‐up, and bioinformatic processing affect the final results, and provide guidelines for reliable study of environmental samples.

We evaluate the performance of four primer sets targeting COI and 16S regions characterizing arthropod diversity in bat faecal samples, and investigate how metabarcoding results are affected by parameters including: (1) number of PCR replicates per sample, (2) sequencing depth, (3) PCR replicate processing strategy (i.e. either additively, by combining the sequences obtained from the PCR replicates, or restrictively, by only retaining sequences that occur in multiple PCR replicates for each sample), (4) minimum copy number for sequences to be retained, (5) chimera removal, and (6) similarity thresholds for Operational Taxonomic Unit (OTU) clustering. Lastly, we measure within‐ and between‐taxa dissimilarities when using sequences from public databases to determine the most appropriate thresholds for OTU clustering and taxonomy assignment.

Our results show that the use of multiple primer sets reduces taxonomic biases and increases taxonomic coverage. Taxonomic profiles resulting from each primer set are principally affected by how many PCR replicates are carried out per sample and how sequences are filtered across them, the sequence copy number threshold and the OTU clustering threshold. We also report considerable diversity differences between PCR replicates from each sample. Sequencing depth increases the dissimilarity between PCR replicates unless the bioinformatic strategies to remove allegedly artefactual sequences are adjusted according to the number of analysed sequences. Finally, we show that the appropriate identity thresholds for OTU clustering and taxonomy assignment differ between markers.

Metabarcoding of complex environmental samples ideally requires (1) investigation of whether more than one primer sets targeting the same taxonomic group is needed to offset primer biases, (2) more than one PCR replicate per sample, (3) bioinformatic processing of sequences that balance diversity detection with removal of artefactual sequences, and (4) empirical selection of OTU clustering and taxonomy assignment thresholds tailored to each marker and the obtained taxa.
Heavy alcohol consumption increases the risk of active tuberculosis in Taiwanese adults: a nation‐wide population‐based cohort study
Authors: Yen Yung‐Feng , Hu Hsiao‐Yun , Lee Ya‐Ling , Ku Po‐Wen , Chuang Pei‐Hung , Lai Yun‐Ju , Chu Dachen
Published: July 2017

Aims

To investigate the impact of alcohol exposure on tuberculosis (TB) development in Taiwanese adults.

Design

Participants from the Taiwan National Health Interview Survey. Alcohol consumption and other covariates were collected by in‐person interviews at baseline. Incident cases of active TB were identified from the National Health Insurance database. A multivariable Cox regression model was used to estimate the association between alcohol consumption and active TB, with adjustment for age, sex, smoking, socio‐economic status and other covariates.

Setting

Taiwan National Health Interview Survey.

Participants

A total of 46 196 adult participants aged ≥ 18 years from three rounds (2001, 2005, 2009) of the Taiwan National Health Interview Survey.

Measurements

Alcohol consumption was classified into never, social, regular or heavy alcohol use. Heavy alcohol consumption was defined as intoxication at least once/week.

Findings

Of the 46 196 study subjects, 61.8, 24.2, 13.5 and 0.5% were classified as never, social, regular and heavy alcohol users, respectively. During the 398 443 person‐years of follow‐up, 279 (0.60%) subjects developed new‐onset active TB. After adjusting for the subject demographics and comorbidities, heavy [hazard ratio (HR) = 5.27; 95% confidence interval (CI) = 2.51–11.09] and regular alcohol users (HR = 1.80; 95% CI = 1.32–2.45) had increased risks of incident TB compared to never users. Moreover, a positive trend between increasing levels of alcohol consumption and the risk of active TB was noted (P < 0.001).

Conclusions

In Taiwan, heavy and regular alcohol consumption are associated with higher risks of active tuberculosis.
Hospitalization rates during potentially inappropriate medication use in a large population‐based cohort of older adults
Authors: Varga Stefan , Alcusky Matthew , Keith Scott W. , Hegarty Sarah E. , Del Canale Stefano , Lombardi Marco , Maio Vittorio
Published: July 2017

Background and aims

The temporal relationship between potentially inappropriate medication (PIM) use and hospitalization remains uncertain. We examined whether current PIM use increases the rate of hospitalization and estimated the rate of hospitalization during exposure to individual PIMs.

Methods

A retrospective population‐based cohort study of 1 480 137 older adults was conducted using the 2003–2013 Italian Emilia‐Romagna Regional administrative healthcare database (~4.5 million residents), which includes demographic, hospital and outpatient prescription information. Each day of follow‐up was defined as exposed/unexposed to PIMs that ‘should always be avoided’, according to the Maio criteria, an Italian modified version of the Beers criteria. The study outcome was all‐cause hospitalizations. Crude PIM‐related hospitalization rates were calculated for individual PIMs. Repeated‐events Cox proportional hazards models with time‐dependent covariates estimated adjusted hazard ratios for hospitalization during PIM exposure, as defined by three versions of the Maio criteria (v2007, v2011, v2014).

Results

During >10 million person‐years of follow‐up, 54.2% of individuals used ≥1 PIM and 10.9% of all person‐time was exposed to v2014 PIMs. Among 1 604 901 hospitalizations, 15.6% occurred during v2014 PIM exposure. Crude hospitalization rates during v2014 PIM‐exposed and unexposed person‐time were 228.1 and 152.1 per 1000 person‐years, respectively. The PIM with the highest rate of hospitalization was ketorolac, while nonsteroidal anti‐inflammatory drugs had the most exposure time. The hazard of hospitalization was 16% greater (hazard ratio = 1.16; 95% confidence interval 1.14, 1.18) among patients exposed to v2014 PIMs. The v2007 and v2011 estimates were similar.

Conclusions

In this large population‐based cohort of older adults, we found a 16% increased hospitalization risk associated with PIM exposure.
Preparation, characterization, and in vitro evaluation of isoniazid and rifampicin‐loaded archaeosomes
Authors: Attar Azade , Bakir Ceren , Yuce‐Dursun Basak , Demir Serap , Cakmakci Emrah , Danis Ozkan , Birbir Meral , Ogan Ayse
Published: July 2017

The ability of Archaea to adapt their membrane lipid compositions to extreme environments has brought in archaeosomes into consideration for the development of drug delivery systems overcoming the physical, biological blockades that the body exhibits against drug therapies. In this study, we prepared unilamellar archaeosomes, from the polar lipid fraction extracted from Haloarcula 2TK2 strain, and explored its potential as a drug delivery vehicle. Rifampicin and isoniazid which are conventional drugs in tuberculosis medication were loaded separately and together in the same archaeosome formulation for the benefits of the combined therapy. Particle size and zeta potential of archaeosomes were measured by photon correlation spectroscopy, and the morphology was assessed by with an atomic force microscope. Encapsulation efficiency and loading capacities of the drugs were determined, and in vitro drug releases were monitored spectrophotometrically. Our study demonstrates that rifampicin and isoniazid could be successfully loaded separately and together in archaeosomes with reasonable drug‐loading and desired vesicle‐specific characters. Both of the drugs had greater affinity for archaeosomes than a conventional liposome formulation. The results imply that archaeosomes prepared from extremely halophilic archaeon were compatible with the liposomes for the development of stable and sustained release of antituberculosis drugs.
Tuberous sclerosis complex: Recent advances in manifestations and therapy
Authors: Wataya‐Kaneda Mari , Uemura Motohide , Fujita Kazutoshi , Hirata Haruhiko , Osuga Keigo , Kagitani‐Shimono Kuriko , Nonomura Norio ,   the Tuberous Sclerosis Complex Board of Osaka University Hospital
Published: July 2017

Tuberous sclerosis complex is an autosomal dominant inherited disorder characterized by generalized involvement and variable manifestations with a birth incidence of 1:6000. In a quarter of a century, significant progress in tuberous sclerosis complex has been made. Two responsible genes, TSC1 and TSC2, which encode hamartin and tuberin, respectively, were discovered in the 1990s, and their functions were elucidated in the 2000s. Hamartin–Tuberin complex is involved in the phosphoinositide 3‐kinase–protein kinase B–mammalian target of rapamycin signal transduction pathway, and suppresses mammalian target of rapamycin complex 1 activity, which is a center for various functions. Constitutive activation of mammalian target of rapamycin complex 1 causes variable manifestations in tuberous sclerosis complex. Recently, genetic tests were launched to diagnose tuberous sclerosis complex, and mammalian target of rapamycin complex 1 inhibitors are being used to treat tuberous sclerosis complex patients. As a result of these advances, new diagnostic criteria have been established and an indispensable new treatment method; that is, “a cross‐sectional medical examination system,” a system to involve many experts for tuberous sclerosis complex diagnosis and treatments, was also created. Simultaneously, the frequency of genetic tests and advances in diagnostic technology have resulted in new views on symptoms. The numbers of tuberous sclerosis complex patients without neural symptoms are increasing, and for these patients, renal manifestations and pulmonary lymphangioleiomyomatosis have become important manifestations. New concepts of tuberous sclerosis complex‐associated neuropsychiatric disorders or perivascular epithelioid cell tumors are being created. The present review contains a summary of recent advances, significant manifestations and therapy in tuberous sclerosis complex.
The functional variant rs34330 of CDKN1B is associated with risk of neuroblastoma
Authors: Capasso Mario , McDaniel Lee D. , Cimmino Flora , Cirino Andrea , Formicola Daniela , Russell Mike R. , Raman Pichai , Cole Kristina A. , Diskin Sharon J.
Published: July 2017

The genetic aetiology of sporadic neuroblastoma is still largely unknown. We have identified diverse neuroblastoma susceptibility loci by genomewide association studies (GWASs); however, additional SNPs that likely contribute to neuroblastoma susceptibility prompted this investigation for identification of additional variants that are likely hidden among signals discarded by the multiple testing corrections used in the analysis of genomewide data. There is evidence suggesting the CDKN1B, coding for the cycle inhibitor p27Kip1, is involved in neuroblastoma. We thus assess whether genetic variants of CDKN1B are associated with neuroblastoma. We imputed all possible genotypes across CDKN1B locus on a discovery case series of 2101 neuroblastoma patients and 4202 genetically matched controls of European ancestry. The most significantly associated rs34330 was analysed in an independent Italian cohort of 311 cases and 709 controls. In vitro functional analysis was carried out in HEK293T and in neuroblastoma cell line SHEP‐2, both transfected with pGL3‐CDKN1B‐CC or pGL3‐CDKN1B‐TT constructs. We identified an association of the rs34330 T allele (‐79C/T) with the neuroblastoma risk (Pcombined = 0.002; OR = 1.17). The risk allele (T) of this single nucleotide polymorphism led to a lower transcription rate in cells transfected with a luciferase reporter driven by the polymorphic p27Kip1 promoter (P < 0.05). Three independent sets of neuroblastoma tumours carrying ‐79TT genotype showed a tendency towards lower CDKN1B mRNA levels. Our study shows that a functional variant, associated with a reduced CDKN1B gene transcription, influences neuroblastoma susceptibility.
Genotypic diversity in root‐endophytic fungi reflects efficient dispersal and environmental adaptation
Authors: Glynou Kyriaki , Ali Tahir , Kia Sevda Haghi , Thines Marco , Maciá‐Vicente Jose G.
Published: July 2017

Studying community structure and dynamics of plant‐associated fungi is the basis for unravelling their interactions with hosts and ecosystem functions. A recent sampling revealed that only a few fungal groups, as defined by internal transcribed spacer region (ITS) sequence similarity, dominate culturable root endophytic communities of nonmycorrhizal Microthlaspi spp. plants across Europe. Strains of these fungi display a broad phenotypic and functional diversity, which suggests a genetic variability masked by ITS clustering into operational taxonomic units (OTUs). The aims of this study were to identify how genetic similarity patterns of these fungi change across environments and to evaluate their ability to disperse and adapt to ecological conditions. A first ITS‐based haplotype analysis of ten widespread OTUs mostly showed a low to moderate genotypic differentiation, with the exception of a group identified as Cadophora sp. that was highly diverse. A multilocus phylogeny based on additional genetic loci (partial translation elongation factor 1α, beta‐tubulin and actin) and amplified fragment length polymorphism profiling of 185 strains representative of the five dominant OTUs revealed a weak association of genetic differences with geography and environmental conditions, including bioclimatic and soil factors. Our findings suggest that dominant culturable root endophytic fungi have efficient dispersal capabilities, and that their distribution is little affected by environmental filtering. Other processes, such as inter‐ and intraspecific biotic interactions, may be more important for the local assembly of their communities.
Self-organization of maze-like structures via guided wrinkling
Authors: Bae Hyung Jong , Bae Sangwook , Yoon Jinsik , Park Cheolheon , Kim Kibeom , Kwon Sunghoon , Park Wook
Published: July 2017

A novel self-organization approach for constructing maze-like structures is presented by controlling wrinkling on a microparticle.
C reactive protein in healthy term newborns during the first 48 hours of life
Authors: Perrone Serafina , Lotti Federica , Longini Mariangela , Rossetti Annalisa , Bindi Ilaria , Bazzini Francesco , Belvisi Elisa , Sarnacchiaro Pasquale , Scapellato Carlo , Buonocore Giuseppe
Published: July 2017

Background

Early-onset neonatal sepsis (EOS) is a serious and potentially life-threatening disease in newborns. C reactive protein (CRP) is the most used laboratory biomarker for the detection of EOS. Little is known about normal reference values of CRP during the perinatal period as several factors are able to influence it.

Objectives

To identify an appropriate range of CRP values in healthy term newborns during the first 48 hours of life.

Design

CRP determination was performed in 859 term newborns at 12, 24 and 48 hours of life. Mode of delivery, maternal vaginal culture results, intrapartum antimicrobial prophylaxis (IAP) and other perinatal variables were recorded.

Results

CRP mean values were significantly higher at 48 hours (4.10 mg/L) than at both 24 (2.30 mg/L) and 12 hours of life (0.80 mg/L). CRP levels were affected by a number of perinatal proinflammatory variables. In particular, CRP mean values were significantly higher in babies born by vaginal delivery (3.80 mg/L) and emergency caesarean section (3.60 mg/L) than in babies born by elective caesarean section (2.10 mg/L). Completed course of IAP led to lower CRP mean values (2.90 mg/L) than IAP not completed (3.80 mg/L) or not performed (4.70 mg/L).

Conclusions

Postnatal age and mode of delivery significantly influence CRP values. Reliable reference values are crucial in order to obtain an adequate diagnostic accuracy.
Listening panel agreement and characteristics of lung sounds digitally recorded from children aged 1–59 months enrolled in the Pneumonia Etiology Research for Child Health (PERCH) case–control study
Authors: McCollum Eric D , Park Daniel E , Watson Nora L , Buck W Chris , Bunthi Charatdao , Devendra Akash , Ebruke Bernard E , Elhilali Mounya , Emmanouilidou Dimitra , Garcia-Prats Anthony J , Githinji Leah , Hossain Lokman , Madhi Shabir A , Moore David P , Mulindwa Justin , Olson Dan , Awori Juliet O , Vandepitte Warunee P , Verwey Charl , West James E , Knoll Maria D , O'Brien Katherine L , Feikin Daniel R , Hammitt Laura L
Published: July 2017

Introduction

Paediatric lung sound recordings can be systematically assessed, but methodological feasibility and validity is unknown, especially from developing countries. We examined the performance of acoustically interpreting recorded paediatric lung sounds and compared sound characteristics between cases and controls.

Methods

Pneumonia Etiology Research for Child Health staff in six African and Asian sites recorded lung sounds with a digital stethoscope in cases and controls. Cases aged 1–59 months had WHO severe or very severe pneumonia; age-matched community controls did not. A listening panel assigned examination results of normal, crackle, wheeze, crackle and wheeze or uninterpretable, with adjudication of discordant interpretations. Classifications were recategorised into any crackle, any wheeze or abnormal (any crackle or wheeze) and primary listener agreement (first two listeners) was analysed among interpretable examinations using the prevalence-adjusted, bias-adjusted kappa (PABAK). We examined predictors of disagreement with logistic regression and compared case and control lung sounds with descriptive statistics.

Results

Primary listeners considered 89.5% of 792 case and 92.4% of 301 control recordings interpretable. Among interpretable recordings, listeners agreed on the presence or absence of any abnormality in 74.9% (PABAK 0.50) of cases and 69.8% (PABAK 0.40) of controls, presence/absence of crackles in 70.6% (PABAK 0.41) of cases and 82.4% (PABAK 0.65) of controls and presence/absence of wheeze in 72.6% (PABAK 0.45) of cases and 73.8% (PABAK 0.48) of controls. Controls, tachypnoea,>3 uninterpretable chest positions, crying, upper airway noises and study site predicted listener disagreement. Among all interpretable examinations, 38.0% of cases and 84.9% of controls were normal (p<0.0001); wheezing was the most common sound (49.9%) in cases.

Conclusions

Listening panel and case–control data suggests our methodology is feasible, likely valid and that small airway inflammation is common in WHO pneumonia. Digital auscultation may be an important future pneumonia diagnostic in developing countries.