bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of net community production and calcification of a coral reef using a boundary layer approach
Authors: Takeshita Yuichiro , McGillis Wade , Briggs Ellen M. , Carter Amanda L. , Donham Emily M. , Martz Todd R. , Price Nichole N. , Smith Jennifer E.
Published: July 2016

Coral reefs are threatened worldwide, and there is a need to develop new approaches to monitor reef health under natural conditions. Because simultaneous measurements of net community production (NCP) and net community calcification (NCC) are used as important indicators of reef health, tools are needed to assess them in situ. Here we present the Benthic Ecosystem and Acidification Measurement System (BEAMS) to provide the first fully autonomous approach capable of sustained, simultaneous measurements of reef NCP and NCC under undisturbed, natural conditions on time scales ranging from tens of minutes to weeks. BEAMS combines the chemical and velocity gradient in the benthic boundary layer to quantify flux from the benthos for a variety of parameters to measure NCP and NCC. Here BEAMS was used to measure these rates from two different sites with different benthic communities on the western reef terrace at Palmyra Atoll for 2 weeks in September 2014. Measurements were made every ∼15 min. The trends in metabolic rates were consistent with the benthic communities between the two sites with one dominated by fleshy organisms and the other dominated by calcifiers (degraded and healthy reefs, respectively). This demonstrates the potential utility of BEAMS as a reef health monitoring tool. NCP and NCC were tightly coupled on time scales of minutes to days, and light was the primary driver for the variability of daily integrated metabolic rates. No correlation between CO2 levels and daily integrated NCC was observed, indicating that NCC at these sites were not significantly affected by CO2.
Revisiting salt marsh resilience to sea level rise: Are ponds responsible for permanent land loss?
Authors: Mariotti G.
Published: July 2016

Ponds are unvegetated rounded depressions commonly present on marsh platforms. The role of ponds on the long‐term morphological evolution of tidal marshes is unclear—at times ponds expand but eventually recover the marsh platform, at other times ponds never recover and lead to permanent marsh loss. Existing field observations indicate that episodic disturbances of the marsh vegetation cause the formation of small (1–10 m) isolated ponds, even if the vegetated platform keeps pace with relative sea level rise (RSLR) and that isolated ponds tend to deepen and enlarge until they eventually connect to the channel network. Here I implement a simple model to study the vertical and planform evolution of a single connected pond. A newly connected pond recovers if its bed lies above the limit for marsh plant growth or if the inorganic deposition rate is larger than the RSLR rate. A pond that cannot accrete faster than RSLR will deepen and enlarge, eventually entering a runaway erosion by wave edge retreat. A large tidal range, a large sediment supply, and a low rate of RSLR favor pond recovery. The model suggests that inorganic sediment deposition alone controls pond recovery, even in marshes where organic matter dominates accretion of the vegetated platform. As such, halting permanent marsh loss by pond collapse requires to increase inorganic sediment deposition. Because pond collapse is possible even if the vegetated platform keeps pace with RSLR, I conclude that marsh resilience to RSLR is less than previously quantified.
Foliage/atmosphere exchange of mercury in a subtropical coniferous forest in south China
Authors: Luo Yao , Duan Lei , Driscoll Charles T. , Xu Guangyi , Shao Mengshu , Taylor Mariah , Wang Shuxiao , Hao Jiming
Published: July 2016

Foliage/atmosphere exchange is an important pathway of deposition and loss in the biogeochemical mercury (Hg) cycle of terrestrial ecosystems. The foliage/atmosphere fluxes of Hg0 were observed over four seasons in a Masson pine (Pinus massoniana) forest in south China. Hg0 exchange showed a bidirectional process but without clear compensation point. Hg0 emissions peaked midday in all four seasons, probably associated with Hg photoreduction on needle surface. Peaks in Hg0 adsorption/deposition often occurred in the morning, especially in spring and autumn. Although current‐year needles accumulated Hg at a rate of 19.4 µg m−2 yr−1, they were a net Hg0 source of 1.7 µg m−2 yr−1 to the atmosphere as their release of Hg exceeded inputs. In addition, previous‐year needles emitted Hg0 at an average rate of 9.2 µg m−2 yr−1. Based on the mass balance of Hg in the forest canopy, the dry deposition of Hg was estimated 52.5 µg m−2 yr−1, much higher than the wet deposition (to 14.4 µg m−2 yr−1). Although Hg in the atmosphere is considered the main source of Hg in folia, soil water may contribute to Hg0 emission by plant transpiration. These processes should be further studied in the future.
K
ranz Anatomy and the

C
4

Pathway
Authors: Garner Drake MG , Mure Christopher M , Yerramsetty Pradeep , Berry James O
Published: July 2016

C
4
photosynthesis incorporates novel leaf anatomy, metabolic specialisations and modified gene expression. C
4
plants typically possess a distinctive Kranz leaf anatomy consisting of two photosynthetic cell types. These are bundle sheath (BS) cells that surround the vascular centres, and mesophyll (M) cells that, in turn, surround the BS cells. A more rare form uses compartmentalisation of dimorphic chloroplasts within a single cell type. In C
4
leaves, these structural frameworks functionally separate two sets of carboxylation and decarboxylation reactions. Selective expression of key photosynthesis genes in BS and M cells leads to specific accumulation of key photosynthetic enzymes which catalyse different sets of cell‐type‐specific reactions, enabling these plants to assimilate atmospheric CO
2
with very high efficiency. For some plants, C
4
photosynthesis has facilitated their adaptation to arid conditions, high temperatures and marginal environments. Understanding the basis of this pathway has applications for improvements in agricultural productivity and alternative fuel development.

Key Concepts

C
4
photosynthesis is a carbon concentration mechanism used by some plants to improve the efficiency of photosynthetic carbon fixation.

C
4
photosynthesis incorporates modified leaf morphology, separation of carboxylation and decarboxylation/refixation steps of carbon assimilation, and specialised patterns of cell‐type‐specific gene expression.

The leaves of most C
4
plants possess a Kranz‐type anatomy consisting of bundle sheath and mesophyll cells. A more rare form of this pathway, called single‐cell C
4
, uses partitioning of dimorphic chloroplasts to separate different sets of reactions within a single leaf cell type.

In C
4
leaves, Rubisco is localised only within internalised bundle sheath cells, or internalised chloroplasts, to protect from atmospheric O
2
and limit the oxygenase activity of this enzyme. The initial carbon assimilation enzyme in these leaves is PEPCase, which incorporates CO
2
but not O
2
.

Reactions of C
4
pathway work as a pump to concentrate CO
2
in the vicinity of the internalised Rubisco enzyme. These reduce or eliminate photorespiration, thereby enhancing photosynthetic efficiency.

C
4
plants are more efficient than C
3
plants under arid conditions, including high temperatures and water stress. C
4
plants show increased efficiency of water and nitrogen use, allowing them to outcompete C
3
plants in marginal environments.

Bioengineering of C
4
characteristics into C
3
species has the potential to improve photosynthetic efficiency in crop plants used for food and biofuel.
Protein Kinases: Physiological Roles in Cell Signalling
Authors: Cormier Kevin W. , Woodgett James R.
Published: July 2016

By catalysing reversible phosphorylation of their substrates, protein kinases play pleiotropic roles in cells and act as predominant arbiters in the coordination of cellular responses to their environment. Despite large variation in biological functions between kinases, there is great structural conservation across the human kinome. Besides structural aspects, substrate specificity relies on dynamic factors such as concentration, activity and localisation. This article discusses these fundamental aspects of protein kinases as related to cellular signalling while also taking note of the less commonly discussed members of the class such as pseudokinases and ectokinases. The complexity of signalling networks is demonstrated by a discussion on the crosstalk involved between the metabolic and signal transduction pathways. By having roles in such processes as cell growth, proliferation and death, protein kinases are at the centre of the regulation of the cell and therefore also at the heart of many human diseases when dysregulated.

Key Concepts

Protein kinases are enzymes that catalyse the phosphorylation of a protein substrate.

Reversible phosphorylation is a key feature of cellular signalling.

There are some highly conserved structural motifs across the human kinome despite great differences in biological functions.

Activation of a kinase is dependent upon assembly of the regulatory spine.

Structural and dynamic factors contribute to substrate selectivity.

Kinases are present both within the cell and in extracellular spaces (ectokinases).

Crosstalk with other post‐translational modifications and between other pathways makes protein kinases participants in nearly every physiological process.
Starch Biosynthesis and Degradation in Plants
Authors: Lloyd James R , Kötting Oliver
Published: July 2016

Starch is the main form in which plants store carbon. Its presence and turnover are important for proper plant growth and productivity. The glucose polymers that constitute the semi‐crystalline starch granule are synthesised by the concerted actions of well‐conserved classes of isoforms of starch synthase and starch‐branching enzyme, via a process that also requires the debranching enzyme isoamylase. The degradation of the granule proceeds via different pathways in different types of starch‐storing tissues. The pathway of starch degradation differs between different plant tissues, but has been elucidated in most detail in leaves. The polymer is first phosphorylated to allow access to the insoluble granule by enzymes that cleave bonds between glucose residues. The main product of this degradation is maltose, which is exported into the cytosol before a series of enzymatic steps convert it to sucrose.

Key Concepts

Starch is the main carbon store of most plants.

It is a glucose polymer that is stored as insoluble granules within plastids.

The polymer is composed of two fractions, branched amylopectin and unbranched amylose.

It is synthesised by a number of enzymes that control the amount made, as well as the amounts of amylose and amylopectin.

Starch is synthesised in leaves during the day and is mobilised at night.

The rate of leaf starch degradation at night is closely controlled by mechanisms linked to the circadian clock so that starch is eliminated just before the beginning of day.

Leaf starch degradation involves many enzymes that lead to the production of soluble sugars, mainly maltose.

Maltose is exported into the cytosol where it is converted to sucrose.

Arabidopsis plants in which starch metabolism is impaired grow poorly.

Starch synthesised in leaves is often termed transitory starch, while that in storage organs can be termed storage starch. They are different in terms of the structure of the amylose and amylopectin within them.
Plant Transposable Elements
Authors: Jiang Ning
Published: July 2016

Transposable elements (TEs) were first discovered by Barbara McClintock in maize. As the most abundant and dynamic component of the plant genomes, the activity of TEs is responsible for genome size expansion, alteration of gene expression, duplication and amplification of normal genes. There are many different types of elements in the plant genomes, with each of them occupying a specific niche, including genic regions, intergenic regions and centromeres. Particularly, the centromere‐specific elements may play critical roles in the formation of new plant species. Most TEs are quiescent in normal development but are turned on by various biotic or abiotic stresses, thus favouring the survival of host organisms under undesirable conditions. In addition to their roles in genome evolution, TEs can be useful tools for gene cloning, mapping and transformation.

Key Concepts

Transposable elements are the largest components of plant genomes.

They have target specificity.

Transposable elements play roles in speciation.

Transposition activity is tightly regulated.

Transposable elements influence expression of other genes.

They are genetic and molecular tools.
Early Epigenetic Origins of Adult Disease
Authors: Pinnock Adele G , Ozanne Susan E
Published: July 2016

Our risk of developing traditionally adult‐onset diseases such as type 2 diabetes and heart disease is thought to be determined by a combination of environmental and genetic factors. Epigenetics provides a mechanism by which our genes and the environment interact. Evidence arising from both epidemiological and animal studies has recently demonstrated a significant role for early‐life epigenetic mechanisms in the aetiology of adult diseases. Critically, epigenetic modifications have now been demonstrated to persist over multiple generations, highlighting their stability. This emphasises the role of epigenetic mechanisms in the exponential surge in the prevalence of obesity and metabolic syndrome that has occurred in just one generation in humans. Future studies should focus further on the precise mechanisms leading to adverse epigenetic alterations that promote disease. A deeper understanding of these processes may lead to effective early‐life interventions which prevent adult‐onset diseases and improve the health of future generations.

Key Concepts

Epigenetics provides a mechanism by which our environment can interact with our genes.

Epigenetic modifications in early life are able to influence the metabolism in later life.

The early environment influences our long‐term health and risk of disease.

Epigenetic modifications may be stable and transmitted through multiple generations.

Epigenetic modifications can be modulated by the early environment.
Stoichiometry and Population Growth in Osmotrophs and Non‐Osmotrophs
Authors: Cherif Mehdi
Published: July 2016

Growth is a process fundamental to life. It implies an increase in not only energy and information but also matter content. Recent advances in ecology have demonstrated that the elemental composition of organisms – their stoichiometry – is inextricably linked to their growth rate. Unbalances between the demands of elements for growth and their relative availabilities often result in elemental limitation. Also, different cellular components have different elemental compositions, and thus changes in allocation between uptake and assembly machineries affect both growth rate and elemental composition at the organismal level. Osmotrophs (including autotrophs) acquire essential elements through a vast set of separate molecules, resulting in more flexible stoichiometries compared to non‐osmotrophs that ingest their preys in one package. Relationships between elemental composition and growth rate should be considered differently for individuals and for populations, as processes and mechanisms differ between the two scales, and more generally among the various biological scales.

Key Concepts

Growth for organisms is by nature a stoichiometric process that involves multiple currencies: energy, information and matter, itself made of multiple essential elements.

Most organisms are stoichiometrically homeostatic, that is, they need to keep the ratios of elements in their protoplasm within narrow limits. However, some organisms use storage structures, such as vacuoles, to further modulate their stoichiometry.

According to Liebig's law of the minimum, growth is mostly limited by the element that is in least supply compared to the demand of the growing organism.

Organisms can resort to a set of behavioural and physiological strategies when facing elemental limitation.

Osmotrophs (including autotrophs), which can regulate the stoichiometry of their diet at the uptake level, differ from non‐osmotrophs (including some large protists and all metazoans), which ingest all the essential elements at once.

Another strategy is to adapt the relative investment into cellular machineries that differ in their elemental composition, but this comes with important repercussions on cellular functions.

Excretion of the elements in excess is another strategy, but there are associated costs, too, leading to only a narrow range of diet elemental composition that optimises growth.

A priori, elemental limitation at the level of populations should differ from limitation of individual growth because of demographic processes.

Even if differences between the two biological levels are ignored, including stoichiometry into classical population models yields interesting novel predictions, confirming the importance of stoichiometry to understand the growth process.
Photoinduced Topographical Feature Development in Blueprinted Azobenzene‐Functionalized Liquid Crystalline Elastomers
Authors: Ahn Suk‐kyun , Ware Taylor H. , Lee Kyung Min , Tondiglia Vincent P. , White Timothy J.
Published: July 2016

All‐optical deformation and recovery of complex topographical features is demonstrated within elastic sheets composed of main‐chain type azobenzene‐functionalized liquid crystalline elastomers (azo‐LCEs). The azo‐LCEs are synthesized via an orthogonal, two‐step reaction between commercially available LC monomers and n‐butylamine. By employing surface alignment, the local orientation of the nematic director is spatially complex (“blueprinted”). Exposing the blueprinted LCE films to light as an actinic stimulus generates a photomechanical response which yields reversible shape changes between 2D and 3D shapes. The deformation of azo‐LCEs strongly depends on the azobenzene concentration as well as the network structure (i.e., crosslink density). Blueprinting complex director profiles within azo‐LCEs yield reconfigurable elastic sheets that can be addressed both remotely and selectively which may have benefit in a variety of applications in aerospace, medicine, and optics.
Phenotype, cancer risk, and surveillance in Beckwith–Wiedemann syndrome depending on molecular genetic subgroups
Authors: Maas Saskia M. , Vansenne Fleur , Kadouch Daniel J. M. , Ibrahim Abdulla , Bliek Jet , Hopman Saskia , Mannens Marcel M. , Merks Johannes H. M. , Maher Eamonn R. , Hennekam Raoul C.
Published: July 2016

Patients with Beckwith–Wiedemann syndrome (BWS) have an increased risk to develop cancer in childhood, especially Wilms tumor and hepatoblastoma. The risk varies depending on the cause of BWS. We obtained clinical and molecular data in our cohort of children with BWS, including tumor occurrences, and correlated phenotype and genotype. We obtained similar data from larger cohorts reported in the literature. Phenotype, genotype and tumor occurrence were available in 229 of our own patients. Minor differences in phenotype existed depending on genotype/epigenotype, similar to earlier studies. By adding patients from the literature, we obtained data on genotype and tumor occurrence of in total 1,971 BWS patients. Tumor risks were highest in the IC1 (H19/IGF2:IG‐DMR) hypermethylation subgroup (28%) and pUPD subgroup (16%) and were lower in the KCNQ1OT1:TSS‐DMR (IC2) subgroup (2.6%), CDKN1C (6.9%) subgroup, and the group in whom no molecular defect was detectable (6.7%). Wilms tumors (median age 24 months) were frequent in the IC1 (24%) and pUPD (7.9%) subgroups. Hepatoblastoma occurred mostly in the pUPD (3.5%) and IC2 (0.7%) subgroups, never in the IC1 and CDKN1C subgroups, and always before 30 months of age. In the CDKN1C subgroup 2.8% of patients developed neuroblastoma. We conclude tumor risks in BWS differ markedly depending on molecular background. We propose a differentiated surveillance protocol, based on tumor risks in the various molecular subgroups causing BWS. © 2016 Wiley Periodicals, Inc.
Annals of morphology fields and prepatterns. Editorial Festschrift for John C. Carey, MD, MPH
Authors: Opitz John M.
Published: July 2016

The investigation of mammalian malformations began to approach human needs in the 19th century with, for example, Meckel's dissection of sibs with the “Meckel” syndrome, his intimation ofHereditätas cause of the condition, his conclusion as to the common causal origin of this specific combination of congenital anomalies, the clear enunciation of the concept of primary malformations, the recognition that many humanmalformationsarenormaldevelopmental states in other animals, and that some were normal anatomical states in remote ancestors and now still normal in collateral descendants (atavisms, Darwin's “reversions”; for example, four wings in dipterans, normal in dragonflies and their common ancestor). Later in the century, Wilhelm His Sr. had proposed a schematic map of “organ‐forming districts” for prospective chick development, a concept that did not sit well with early workers in developmental biology (e.g., Boveri) until methods became available for a direct experimental “attack” on the embryo. This approach was pioneered by Spemann and Mangold through interspecies transplantation of embryonic rudiments with the spectacular result that set the research stage in developmental biology for the next many years. But it was not until mid‐century that the late, great geneticist, Curt Stern, made the His model of chick development more intellectually and experimentally approachable with his meticulous analysis of cuticular appendages ofDrosophila, one bristle and one bristle group (field) at a time, in mosaics or gynandromorphs, leading to the ingenious concept ofprepatterns. As a basic scientist, Stern did not broaden prepatterns into medicine or to human malformations where it has now found a most gratifying application. This contribution to the Carey Festschrift is to summarize, briefly, field and prepattern theory. © 2016 Wiley Periodicals, Inc.
Dehydromicrosclerodermin B and Microsclerodermin J: Total Synthesis and Structural Revision
Authors: Melikhova Ekaterina Y. , Pullin Robert D. C. , Winter Christian , Donohoe Timothy J.
Published: July 2016

The total synthesis of dehydromicrosclerodermin B and microsclerodermin J is described. Efficient approaches to the unusual amino acids in the target molecules were developed on the basis of a Negishi coupling (for Trp‐2‐CO2H) and Blaise reaction (for Pyrr). An incorrect assignment of the pyrrolidinone stereochemistry of both compounds was confirmed by synthesizing epimers of the proposed structures. The spectroscopic data of these epimers were in complete agreement with those for the naturally derived material.
Dispersion‐Force‐Assisted Disproportionation: A Stable Two‐Coordinate Copper(II) Complex
Authors: Wagner Clifton L. , Tao Lizhi , Thompson Emily J. , Stich Troy A. , Guo Jingdong , Fettinger James C. , Berben Louise A. , Britt R. David , Nagase Shigeru , Power Philip P.
Published: July 2016

The synthesis of the first linear coordinated CuII complex Cu{N(SiMe3)Dipp}2 (1 Dipp=C6H5‐2,6Pri2) and its CuI counterpart [Cu{N(SiMe3)Dipp}2]− (2) is described. The formation of 1 proceeds through a dispersion force‐driven disproportionation, and is the reaction product of a CuI halide and LiN(SiMe3)Dipp in a non‐donor solvent. The synthesis of 2 is accomplished by preventing the disproportionation into 1 by using the complexing agent 15‐crown‐5. EPR spectroscopy of 1 provides the first detailed study of a two‐coordinate transition‐metal complex indicating strong covalency in the Cu−N bonds.
Electrophilic Cyanation of Boron Enolates: Efficient Access to Various β‐Ketonitrile Derivatives
Authors: Kiyokawa Kensuke , Nagata Takaya , Minakata Satoshi
Published: July 2016

The highly efficient electrophilic cyanation of boron enolates using readily available cyanating reagents, N‐cyano‐N‐phenyl‐p‐toluenesulfonamide (NCTS) and p‐toluenesulfonyl cyanide (TsCN), is reported. Various β‐ketonitriles were prepared by this new protocol, which has a remarkably broad substrate scope compared to existing methods. The present method also allowed efficient synthesis of β‐ketonitriles containing a quaternary α‐carbon center. In addition, a preliminary result with the use of a chiral boron enolate for the enantioselective cyanation reaction is described.
Method for the synthesis of para‐aramid nanofibers
Authors: Yeager Matthew P. , Hoffman Christopher M. , Xia Zhiyong , Trexler Morgana M.
Published: July 2016

The synthesis and electrospinning of novel N‐substituted aramid nanofibers (ANFs) prepared from basic dispersions of commercial microscale Kevlar fibers are herein reported. The functionalized ANFs were characterized via Fourier transform infrared spectroscopy, 13C solid‐state nuclear magnetic resonance spectroscopy, and X‐ray diffraction to confirm proper N‐substitution of the side groups and to determine changes to the polymer crystallinity and stability. These analyses suggested that the electrospun ANFs consisted of numerous crystalline domains in the transverse fiber direction with large amorphous regions that were void of defects commonly found in commercial Kevlar fibers. A semi‐empirical study of the variations in the solubility parameter due to various side chain moieties was conducted to facilitate solvent selection and to elucidate the enhanced solubility effects with selected organic solvents. These initial findings suggest a promising route for obtaining a new class of nanofibers with ultrahigh strength and stiffness. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44082.
Boundary Control for A Flexible Inverted Pendulum System Based on A Pde Model
Authors: Peng Yawei , Liu Jinkun , He Wei
Published: July 2016

A partial differential equation (PDE) model for a flexible inverted pendulum system (FIPS) is derived by the use of the Hamilton principle. To solve the coupling system model, a singular perturbation method was adopted. The PDE model was divided into a fast subsystem and a slow subsystem using the singular perturbation method. To stabilize the fast subsystem, a boundary control force was applied at the free end of the beam. It then was proven that the closed‐loop subsystem is appropriate and exponentially stable. For the slow subsystem, a sliding mode control method was employed to design a controller and the Linear Matrix Inequality (LMI) method was used to design the sliding surface. It then was shown that the slow subsystem is exponentially stable.
A Family of Robust Simultaneous Controllers With Tuning Parameters Design for a Set of Port‐Controlled Hamiltonian Systems
Authors: Cao Zhong , Hou Xiaorong , Zhao Wenjing
Published: July 2016

This paper investigates the robust simultaneous stabilization (RSS) and robust adaptive simultaneous stabilization (RASS) problem for a set of port‐controlled Hamiltonian (PCH) systems. Some results for designing a family of robust simultaneous controllers with tuning parameters for such systems are proposed. Firstly, using the dissipative Hamiltonian structural properties, these systems are combined to generate an augmented PCH system, and two simultaneous stabilization controllers with parameters are designed for the systems: one is a robust controller and the other is adaptive. Secondly, an algorithm for solving the tuning parameters’ ranges of controller is proposed with symbolic computation. Finally, a numerical example is studied by applying the method obtained in this paper to a set of PCH systems with external disturbance. The effectiveness of the proposed control method is verified by simulations. Compared with conventional simultaneous stabilization control, the controller obtained in this paper not only has strong robustness for a set of systems, but also can optimize the robustness for the systems by adjusting the parameters’ values.
Salivary cortisol and behavioral response to social evaluative threat in adolescents with autism spectrum disorder
Authors: Edmiston E. Kale , Blain Scott D. , Corbett Blythe A.
Published: July 2016

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social behavior. One possible explanation for social communication deficits in ASD could be differences in biological systems that support responses to environmental stimuli. If so, it is unclear if differences in the arousal response to social stimuli in ASD are due to reduced interest in social information, or to an increased stress response. The hypothalamic pituitary adrenal axis facilitates arousal and the stress response to sensory input, including social stimuli. Previous research shows blunted cortisol response to social evaluative threat in children with ASD. The majority of prior work has focused on children with ASD, but adolescents with ASD are understudied. The adolescent period is of interest, as this developmental epoch is associated with increased salience of social evaluative threat in typically developing (TD) populations. In this study, we employed the Trier Social Stress Test (TSST), a laboratory paradigm that involves exposure to social evaluative threat, to study the cortisol and behavioral response to social evaluative threat in ASD and TD adolescents. Salivary cortisol data were collected at six time points before and after the TSST. Behavioral data were collected using video recordings of the TSST, which were then operationalized and coded. Paired sample t‐tests were used to calculate within‐group cortisol response to the TSST. Cortisol significantly increased in response to the TSST in the TD group but not the ASD group. The TD group showed a trend for more self‐soothing behaviors during the stressor than the ASD group. The lack of a cortisol response to the TSST in the ASD group suggests that the TSST is not interpreted as stressful or salient for ASD adolescents. Autism Res 2017, 10: 346–358. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Non‐ASD outcomes at 36 months in siblings at familial risk for autism spectrum disorder (ASD): A baby siblings research consortium (BSRC) study
Authors: Charman Tony , Young Gregory S. , Brian Jessica , Carter Alice , Carver Leslie J. , Chawarska Katarzyna , Curtin Suzanne , Dobkins Karen , Elsabbagh Mayada , Georgiades Stelios , Hertz‐Picciotto Irva , Hutman Ted , Iverson Jana M. , Jones Emily J. , Landa Rebecca , Macari Suzanne , Messinger Daniel S. , Nelson Charles A. , Ozonoff Sally , Saulnier Celine , Stone Wendy L. , Tager‐Flusberg Helen , Webb Sara Jane , Yirmiya Nurit , Zwaigenbaum Lonnie
Published: July 2016

We characterized developmental outcomes of a large sample of siblings at familial high‐risk of autism spectrum disorder (ASD), who themselves did not have ASD (n = 859), and low‐risk controls with no family history of ASD (n = 473). We report outcomes at age 3 years using the Mullen Scales of Early Learning, the Autism Diagnostic Observation Schedule (ADOS), the Autism Diagnostic Interview—Revised (ADI‐R) and adaptive functioning on the Vineland Adaptive Behavior Scales. Around 11% of high‐risk siblings had mild‐to‐moderate levels of developmental delay, a rate higher than the low‐risk controls. The groups did not differ in the proportion of toddlers with mild‐to‐moderate language delay. Thirty percent of high‐risk siblings had elevated scores on the ADOS, double the rate seen in the low‐risk controls. High‐risk siblings also had higher parent reported levels of ASD symptoms on the ADI‐R and lower adaptive functioning on the Vineland. Males were more likely to show higher levels of ASD symptoms and lower levels of developmental ability and adaptive behavior than females across most measures but not mild‐to‐moderate language delay. Lower maternal education was associated with lower developmental and adaptive behavior outcomes. These findings are evidence for early emerging characteristics related to the “broader autism phenotype” (BAP) previously described in older family members of individuals with ASD. There is a need for ongoing clinical monitoring of high‐risk siblings who do not have an ASD by age 3 years, as well as continued follow‐up into school age to determine their developmental and behavioral outcomes. Autism Res 2017, 10: 169–178. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Cover Image, Volume 10, Issue 4
Authors: Ahmad Farah B , Zhang Zhanying , Doherty William OS , O'Hara Ian M
Published: July 2016

The cover image, by Farah Binti Ahmad et al., is based on the Modeling and Analysis Evaluation of oil production from oil palm empty fruit bunch by oleaginous microorganisms, DOI: 10.1002/bbb.1645. Photo Credit: Farah Binti Ahmad.

image
In vivo individual variations in pharmacokinetics of efavirenz in cynomolgus monkeys genotyped for cytochrome P450 2C9
Authors: Iwasaki Kazuhide , Kitsugi Yusuke , Ikeda Kanami , Yoshikawa Takahiro , Hosaka Shinya , Uehara Shotaro , Uno Yasuhiro , Utoh Masahiro , Yamazaki Hiroshi
Published: July 2016

Cynomolgus monkeys are used frequently in preclinical studies for new drug development due to their evolutionary closeness to humans. An antiretroviral drug, efavirenz, is a typical probe substrate for human cytochrome P450 (P450) 2B6, but is mainly metabolized by cynomolgus monkey P450 2C9. In this study, plasma concentrations of efavirenz were assessed in six cynomolgus monkeys genotyped for P450 2C9 c.334 A > C (I112L) (three wild‐type, one heterozygote and two homozygotes) by high performance liquid chromatography with tandem mass spectrometry. After intravenous administration at a dose of 1.0 mg/kg, biphasic plasma elimination curves of efavirenz were seen in these cynomolgus monkeys. The mean plasma concentration of the primary metabolite 8‐hydroxyefavirenz (1 h after treatment, with hydrolysis by β‐glucuronidase) in the wild‐type group was significantly higher (4.0‐fold) than the combined heterozygous and homozygous group mean. The area under the plasma concentration–time curve value of efavirenz in the homozygous group after oral administration at a dose of 2.0 mg/kg was significantly higher (2.0‐fold) than the combined wild‐type and heterozygous group. These results collectively indicated that P450 2C9 c.334 A > C (I112L) variation was associated with efavirenz metabolic clearance in vivo. Cynomolgus P450 2C9 polymorphism might account for interindividual variations of efavirenz metabolism in cynomolgus monkeys. Copyright © 2016 John Wiley & Sons, Ltd.
A 2015 global update on folic acid‐preventable spina bifida and anencephaly
Authors: Arth Annelise , Kancherla Vijaya , Pachón Helena , Zimmerman Sarah , Johnson Quentin , Oakley Godfrey P.
Published: July 2016

Background

Spina bifida and anencephaly are two major neural tube defects. They contribute substantially to perinatal, neonatal, infant, and under‐five mortality and life‐long disability. To monitor the progress toward the total prevention of folic acid‐preventable spina bifida and anencephaly (FAP SBA), we examined their global status in 2015.

Methods

Based on existing data, we modeled the proportion of FAP SBA that are prevented in the year 2015 through mandatory folic acid fortification globally. We included only those countries with mandatory fortification that added at least 1.0 ppm folic acid as a fortificant to wheat and maize flour, and had complete information on coverage. Our model assumed mandatory folic acid fortification at 200 μg/day is fully protective against FAP SBA, and reduces the rate of spina bifida and anencephaly to a minimum of 0.5 per 1000 births.

RESULTS

Our estimates show that, in 2015, 13.2% (35,500 of approximately 268,700 global cases) of FAP SBA were prevented in 58 countries through mandatory folic acid fortification of wheat and maize flour. Most countries in Europe, Africa, and Asia were not implementing mandatory fortification with folic acid.

Conclusion

Knowledge that folic acid prevents spina bifida and anencephaly has existed for 25 years, yet only a small fraction of FAP SBA is being prevented worldwide. Several countries still have 5‐ to 20‐fold epidemics of FAP SBA. Implementation of mandatory fortification with folic acid offers governments a proven and rapid way to prevent FAP SBA‐associated disability and mortality, and to help achieve health‐related Sustainable Development Goals. Birth Defects Research (Part A) 106:520–529, 2016. © 2016 Wiley Periodicals, Inc.
Transmissible cancers in an evolutionary context
Authors: Ujvari Beata , Papenfuss Anthony T. , Belov Katherine
Published: July 2016

Cancer is an evolutionary and ecological process in which complex interactions between tumour cells and their environment share many similarities with organismal evolution. Tumour cells with highest adaptive potential have a selective advantage over less fit cells. Naturally occurring transmissible cancers provide an ideal model system for investigating the evolutionary arms race between cancer cells and their surrounding micro‐environment and macro‐environment. However, the evolutionary landscapes in which contagious cancers reside have not been subjected to comprehensive investigation. Here, we provide a multifocal analysis of transmissible tumour progression and discuss the selection forces that shape it. We demonstrate that transmissible cancers adapt to both their micro‐environment and macro‐environment, and evolutionary theories applied to organisms are also relevant to these unique diseases. The three naturally occurring transmissible cancers, canine transmissible venereal tumour (CTVT) and Tasmanian devil facial tumour disease (DFTD) and the recently discovered clam leukaemia, exhibit different evolutionary phases: (i) CTVT, the oldest naturally occurring cell line is remarkably stable; (ii) DFTD exhibits the signs of stepwise cancer evolution; and (iii) clam leukaemia shows genetic instability. While all three contagious cancers carry the signature of ongoing and fairly recent adaptations to selective forces, CTVT appears to have reached an evolutionary stalemate with its host, while DFTD and the clam leukaemia appear to be still at a more dynamic phase of their evolution. Parallel investigation of contagious cancer genomes and transcriptomes and of their micro‐environment and macro‐environment could shed light on the selective forces shaping tumour development at different time points: during the progressive phase and at the endpoint. A greater understanding of transmissible cancers from an evolutionary ecology perspective will provide novel avenues for the prevention and treatment of both contagious and non‐communicable cancers.
Mechanisms regulating phosphatase specificity and the removal of individual phosphorylation sites during mitotic exit
Authors: Rogers Samuel , McCloy Rachael , Watkins D Neil , Burgess Andrew
Published: July 2016

Entry into mitosis is driven by the activity of kinases, which phosphorylate over 7000 proteins on multiple sites. For cells to exit mitosis and segregate their genome correctly, these phosphorylations must be removed in a specific temporal order. This raises a critical and important question: how are specific phosphorylation sites on an individual protein removed? Traditionally, the temporal order of dephosphorylation was attributed to decreasing kinase activity. However, recent evidence in human cells has identified unique patterns of dephosphorylation during mammalian mitotic exit that cannot be fully explained by the loss of kinase activity. This suggests that specificity is determined in part by phosphatases. In this review, we explore how the physicochemical properties of an individual phosphosite and its surrounding amino acids can affect interactions with a phosphatase. These positive and negative interactions in turn help determine the specific pattern of dephosphorylation required for correct mitotic exit.
Assessing the Within‐Trial Treatment Integrity of Discrete‐Trial Teaching Programs Using Sequential Analysis
Authors: Brand Denys , Mudford Oliver C. , Arnold‐Saritepe Angela , Elliffe Douglas
Published: July 2016

Discrete‐trial teaching is a strategy frequently used to teach functional skills to individuals with developmental and intellectual disabilities. Research has shown that the within‐trial components of the procedure should be administered with ≥90% treatment integrity to facilitate optimal learning. Usually within‐trial treatment integrity is measured using whole‐session methods such as percentage of trials correctly administered. This study demonstrated one‐step Markov transition matrices as a method of assessing within‐trial treatment integrity. All components of discrete trials were coded and time‐stamped from video recordings of therapist–learner dyads in their typical setting (home or school). Several types of within‐trial treatment integrity errors were identified using the Markov transition matrices, error sequences that could not be identified using a percentage correct analysis. Better identification of errors has the potential both to enhance treatment integrity and to gain efficiency by targeted retraining of therapists. Copyright © 2016 John Wiley & Sons, Ltd.
Nanostructured luminescently labeled nucleic acids
Authors: Kricka Larry J. , Fortina Paolo , Park Jason Y.
Published: July 2016

Important and emerging trends at the interface of luminescence, nucleic acids and nanotechnology are: (i) the conventional luminescence labeling of nucleic acid nanostructures (e.g. DNA tetrahedron); (ii) the labeling of bulk nucleic acids (e.g. single‐stranded DNA, double‐stranded DNA) with nanostructured luminescent labels (e.g. copper nanoclusters); and (iii) the labeling of nucleic acid nanostructures (e.g. origami DNA) with nanostructured luminescent labels (e.g. silver nanoclusters). This review surveys recent advances in these three different approaches to the generation of nanostructured luminescently labeled nucleic acids, and includes both direct and indirect labeling methods.
Fluorescence colocalization microscopy analysis can be improved by combining object‐recognition with pixel‐intensity‐correlation
Authors: Moser Bernhard , Hochreiter Bernhard , Herbst Ruth , Schmid Johannes A.
Published: July 2016

The question whether two proteins interact with each other or whether a protein localizes to a certain region of the cell is often addressed with fluorescence microscopy and analysis of a potential colocalization of fluorescence markers. Since a mere visual estimation does not allow quantification of the degree of colocalization, different statistical methods of pixel‐intensity correlation are commonly used to score it. We observed that these correlation coefficients are prone to false positive results and tend to show high values even for molecules that reside in different organelles. Our aim was to improve this type of analysis and we developed a novel method combining object‐recognition based colocalization analysis with pixel‐intensity correlation to calculate an object‐corrected Pearson coefficient. We designed a macro for the Fiji‐version of the software ImageJ and tested the performance systematically with various organelle markers revealing an improved robustness of our approach over classical methods. In order to prove that colocalization does not necessarily mean a physical interaction, we performed FRET (fluorescence resonance energy transfer) microscopy. This confirmed that non‐interacting molecules can exhibit a nearly complete colocalization, but that they do not show any significant FRET signal in contrast to proteins that are bound to each other.
Simultaneous determination of four antiepileptic drugs in human plasma samples using an ultra‐high‐performance liquid chromatography tandem mass spectrometry method and its application in therapeutic drug monitoring
Authors: Dupouey Julien , Doudka Natalia , Belo Séphora , Blin Olivier , Guilhaumou Romain
Published: July 2016

Therapeutic drug monitoring of antiepileptic drugs is widely practiced to achieve optimal efficacy and avoid adverse side effects. We describe an ultra‐high‐performance liquid chromatography tandem mass spectrometry (UHPLC/MS/MS) method developed for the monitoring of four frequently prescribed antiepileptic drugs – lamotrigine, levetiracetam, oxcarbazepine and topiramate. The main pharmacologically active metabolite of oxcarbazepine (mono‐hydroxy‐derivative metabolite, MHD) was also quantified. After addition of internal standards and a simple stage of protein precipitation, plasmatic samples were analyzed on a C18 column. All antiepileptic drugs were separated and quantified in 6 min, without interference. A good linearity was observed all over the calibration range (r2 > 0.99), up to 20 μg/mL (40 μg/mL for MHD). The limit of quantification was 0.20 μg/mL (0.40 μg/mL for MHD) with precision and accuracy ranging from 1.0 to 2.1% and from 96.7 to 110.8%, respectively. Intra‐ and inter‐day precision and accuracy values were within 15%. No significant matrix effect was observed for all analytes. Clinical application was successfully evaluated in 259 samples from patients treated for epilepsy or bipolar disorders. In conclusion, a rapid, specific and sensitive UHPLC/MS/MS method was developed and validated for simultaneous quantification of antiepileptic drugs, suitable for therapeutic drug monitoring in neurology and psychiatry.
Adherence to the World Cancer Research Fund/American Institute for Cancer Research lifestyle recommendations in colorectal cancer survivors: results of the PROFILES registry
Authors: Winkels Renate M. , van Lee Linde , Beijer Sandra , Bours Martijn J. , van Duijnhoven Fränzel J. B. , Geelen Anouk , Hoedjes Meeke , Mols Floortje , de Vries Jeanne , Weijenberg Matty P. , Kampman Ellen
Published: July 2016

We examined adherence to the eight The World Cancer Research Foundation/American Institute for Cancer Research (WCRF/AICR) recommendations on diet, physical activity, and body weight among colorectal cancer survivors, and whether adherence was associated with intention to eat healthy and with the need for dietary advice. Adherence to these recommendations may putatively reduce the risk of recurrence and death. Studies on adherence to these recommendations in colorectal cancer (CRC) survivors are lacking. Adherence was assessed in a cross‐sectional study among 1196 CRC survivors and could range between 0 (no adherence) and 8 points (complete adherence). Participants completed questionnaires on dietary intake, physical activity, and body weight. Prevalence Ratios were calculated to assess whether adherence to recommendations were associated with dietary intentions and needs. Twelve percentage of the survivors adhered to 6 or more recommendations; 65% had a score between >4 and 6 points; 23% scored no more than 4 points. The recommendation for to be modest with consumption of meat showed lowest adherence: 8% adhered; whereas the recommendation not to use dietary supplements showed highest adherence (75%). 18% reported a need for dietary advice, but this was not associated with adherence to recommendations. Survivors with higher adherence reported less often that they had received dietary advice, were less likely to have the intention to eat healthier, but reported more often that they had changed their diet since diagnosis. There is ample room for improvement of lifestyle recommendations in virtually all CRC survivors. A minor part of CRC survivors expressed a need for dietary advice which was not associated with adherence to the recommendations.