bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis, Computational Docking Study, and Biological Evaluation of a Library of Heterocyclic Curcuminoids with Remarkable Antitumor Activity
Authors: Laali Kenneth K. , Greves William J. , Zwarycz Angela T. , Correa Smits Sebastian J. , Troendle Frederick J. , Borosky Gabriela L. , Akhtar Sharoon , Manna Alak , Paulus Aneel , Chanan‐Khan Asher , Nukaya Manabu , Kennedy Gregory D.
Published: August 2018

In a continuing search for curcuminoid (CUR) compounds with antitumor activity, a novel series of heterocyclic CUR–BF2 adducts and CUR compounds based on indole, benzothiophene, and benzofuran along with their aryl pyrazoles were synthesized. Computational docking studies were performed to compare binding efficiency to target proteins involved in specific cancers, namely HER2, proteasome, VEGFR, BRAF, and Bcl‐2, versus known inhibitor drugs. The majority presented very good binding affinities, similar to, and even more favorable than those of known inhibitors. The indole‐based CUR–BF2 and CUR compounds and their bis‐thiocyanato derivatives exhibited high anti‐proliferative and apoptotic activity by in vitro bioassays against a panel of 60 cancer cell lines, more specifically against multiple myeloma (MM) cell lines (KMS11, MM1.S, and RPMI‐8226) with significantly lower IC50 values versus healthy PBMC cells; they also exhibited higher anti‐proliferative activity in human colorectal cancer cells (HCT116, HT29, DLD‐1, RKO, SW837, and Caco2) than the parent curcumin, while showing notably lower cytotoxicity in normal colon cells (CCD112CoN and CCD841CoN).
Experimental Characterization of the Binding Affinities between Proapoptotic BH3 Peptides and Antiapoptotic Bcl‐2 Proteins
Authors: Kong Wenna , Zhou Mi , Li Qing , Fan Wenjie , Lin Haixia , Wang Renxiao
Published: August 2018

The Bcl‐2 family proteins are key regulators of the intrinsic apoptotic pathway and are among the validated targets for developing anticancer drugs. Protein–protein interactions between the pro‐ and antiapoptotic members of this family determine mitochondrial outer‐membrane permeabilization. Elucidating such protein–protein interactions in a quantitative way is helpful for network pharmacology studies on the Bcl‐2 family, which, in turn, will provide valuable guidance for developing new anticancer therapies. In this study, the binding affinities of the BH3 peptides derived from eight proapoptotic BH3‐only proteins (i.e., Bid, Bim, Puma, Noxa, Bad, Bmf, Bik, Hrk) against five well‐studied antiapoptotic proteins (i.e., Bcl‐xL, Bcl‐2, Mcl‐1, Bcl‐w, Bfl‐1) in the Bcl‐2 family have been measured. Three different types of binding assay (i.e., surface plasmon resonance, fluorescence polarization, and homogeneous time‐resolved fluorescence) were employed for cross‐validation. The results confirmed that each proapoptotic BH3 peptide exhibited a distinct binding profile against the five antiapoptotic proteins. The binding data obtained herein serve as a fresh update or correction to existing knowledge. It is expected that such binding data will be helpful for building more accurate mathematical network models for depicting the complex protein–protein interactions within the Bcl‐2 family.
Development of Potent Inhibitors of Fatty Acid Amide Hydrolase Useful for the Treatment of Neuropathic Pain
Authors: Brindisi Margherita , Borrelli Giuseppe , Brogi Simone , Grillo Alessandro , Maramai Samuele , Paolino Marco , Benedusi Mascia , Pecorelli Alessandra , Valacchi Giuseppe , Di Cesare Mannelli Lorenzo , Ghelardini Carla , Allarà Marco , Ligresti Alessia , Minetti Patrizia , Campiani Giuseppe , di Marzo Vincenzo , Butini Stefania , Gemma Sandra
Published: August 2018

The unique role of fatty acid amide hydrolase (FAAH) in terminating endocannabinoid (EC) signaling supports its relevance as a therapeutic target. Inhibition of EC metabolizing enzymes elicits indirect agonism of cannabinoid receptors (CBRs) and therapeutic efficacy devoid of psychotropic effects. Based on our previous ligands, and aiming at the discovery of new selective FAAH inhibitors, we developed a series of 12 new compounds characterized by functionalized tricyclic scaffolds. All the developed compounds display negligible activity on monoacylglycerol lipase (MAGL) and CBRs. The most potent FAAH inhibitors of the newly developed series, 6‐oxo‐5,6‐dihydro‐4H‐benzo[f]pyrrolo[1,2‐a][1,4]diazepin‐9‐yl‐6‐phenylhexylcarbamate (5 h) and 4‐oxo‐5,6‐dihydro‐4H‐benzo[f]pyrrolo[1,2‐a][1,4]diazepin‐9‐yl‐(6‐phenylhexyl)carbamate (5 i) (nanomolar FAAH inhibitors, the latter of which also shows micromolar affinity at the CB1R), were selected for further studies. Results of cell‐based studies on a neuroblastoma cell line (IMR32) demonstrated 5 h, 5 i, and our reference compound 3 ([3‐(3‐carbamoylpyrrol‐1‐yl)phenyl] N‐(5‐phenylpentyl)carbamate) to lack any cytotoxic effect, while all three showed the ability to decrease oxidative stress by reducing the expression of the redox‐sensitive transcription factor NF‐κB. Encouraged by these data, these compounds were studied in vivo and were dosed orally in a mouse model of neuropathic pain. At 10 mg kg−1 all the compounds were able to relieve the hypersensitivity induced by oxaliplatin.
Childhood trauma is predictive for clinical staging, alcohol consumption, and emotional symptoms in patients with head and neck cancer
Authors: Sarafim‐Silva Bruna Amélia M. , Duarte Gabrielle D. , Sundefeld Maria Lúcia M. M. , Biasoli Éder Ricardo , Miyahara Glauco I. , Bernabé Daniel Galera
Published: August 2018

BACKGROUND

Traumatic events in childhood have been associated with the occurrence of anxiety and depression in adulthood. This relation has been investigated in patients with breast cancer; however, it has been little explored in patients with other types of cancer. The objective of this study was to evaluate the occurrence of childhood trauma in patients with head and neck cancer and its association with clinicopathological variables and anxiety and depression levels.

METHODS

The study included 110 patients with head and neck squamous cell carcinoma (HNSCC) before they started cancer treatment. Clinicopathological and biobehavioral data were collected from patients' medical records. Anxiety and depression levels were assessed with the Beck Anxiety Inventory and the Beck Depression Inventory, respectively. The Childhood Trauma Questionnaire was used to evaluate the occurrence of traumatic events in childhood.

RESULTS

One hundred five patients (95.5%) experienced at least 1 type of childhood trauma. Emotional neglect was the most reported childhood trauma (43.8%), and multiple regression revealed that it was an independent variable for advanced clinical staging (β = 2.15, P = .048) and higher alcohol consumption (β = 2.32, P = .031). Patients with HNSCC who experienced more traumatic events in childhood had an almost 12 times greater chance of increased depression levels during the pretreatment period (β = 11.89; P = .0002). The occurrence of physical child neglect was a predictive factor for increased anxiety levels (β = 4.17, P = 0.029).

CONCLUSIONS

Traumatic events in childhood are predictive for advanced clinical staging, alcohol consumption, and emotional symptoms in patients with HNSCC, and they should be considered in clinical and psychological intervention strategies during cancer treatment. Cancer 2018;000:000‐000. © 2018 American Cancer Society.
Quantifying the Proteolytic Cleavage of Plasma Membrane Proteins in Living Cells
Authors: Calamai Martino , Pavone Francesco Saverio
Published: August 2018

The standard approach to study the activity of proteases consists of lysing cells and measuring the changes in the fluorescence properties of a synthetic substrate after cleavage in vitro. Here, a general protocol that uses a bi‐fluorescent chimeric construct of a known substrate protein that follows the proteolytic processing in living cells is described. This approach is useful, in particular, to search for pharmacological conditions altering the cleavage rate of a certain protease, or to investigate the biological factors influencing a certain proteolytic mechanism. Three different methods (microscopy, flow cytometry, and spectroscopy) to detect fluorescence changes due to alteration in the processing are described. This approach was originally developed for studying conditions affecting the proteolytic activity of the β‐secretase Bace1 on the amyloid precursor protein APP, but can in principle be applied to investigate any membrane protein undergoing ectodomain shedding by proteolytic cleavage. © 2018 by John Wiley & Sons, Inc.
Silicon photonic networks: Signal loss and power challenges
Authors: Crespo Juan‐Jose , Sánchez José L. , Alfaro‐Cortés Francisco J.
Published: August 2018

Exascale systems are in need for alternative interconnection technologies. Electrical interconnects are not likely to scale well to a large number of computing nodes in terms of energy efficiency and latency. Silicon photonic networks stand as the main alternative to solve this problem, but are we there yet? In this paper, we exhibit some challenges to be solved for this technology to become a viable solution. Signal loss sources play a critical role in photonic network designs as they restrict the ability to perform data transmission in an effective way.
Arginine Side‐Chain Hydrogen Exchange: Quantifying Arginine Side‐Chain Interactions in Solution
Authors: Mackenzie Harold W. , Hansen D. Flemming
Published: August 2018

The rate with which labile backbone hydrogen atoms in proteins exchange with the solvent has long been used to probe protein interactions in aqueous solutions. Arginine, an essential amino acid found in many interaction interfaces, is capable of an impressive range of interactions via its guanidinium group. The hydrogen exchange rate of the guanidinium hydrogens therefore becomes an important measure to quantify side‐chain interactions. Herein we present an NMR method to quantify the hydrogen exchange rates of arginine side‐chain 1Hϵ protons and thus present a method to gauge the strength of arginine side‐chain interactions. The method employs 13C‐detection and the one‐bond deuterium isotope shift observed for 15Nϵ to generate two exchanging species in 1H2O/2H2O mixtures. An application to the protein T4 Lysozyme is shown, where protection factors calculated from the obtained exchange rates correlate well with the interactions observed in the crystal structure. The methodology presented provides an important step towards characterising interactions of arginine side‐chains in enzymes, in phase separation, and in protein interaction interfaces in general.
Putting the Disulfide Bridge at Risk: How UV‐C Radiation Leads to Ultrafast Rupture of the S‐S Bond
Authors: Larsen Martin A. B. , Skov Anders B. , Clausen Christian M. , Ruddock Jennifer , Stankus Brian , Weber Peter M. , Sølling Theis I.
Published: August 2018

We investigate the ultrafast photoinduced dynamics of the cyclic disulfide 1,2‐dithiane upon 200 nm excitation by time‐resolved photoelectron spectroscopy and show that the S−S bond breaks on an ultrafast time scale. This stands in stark contrast to excitation at longer wavelengths where the initially excited S1 state evolves as the wavepacket is guided towards a conical intersection with S0 by a torsional motion involving a partially broken bond between the sulfur atoms. This process at lower excitation energy allows for efficient (re‐)population of S0, rendering dithiane intact. At 200 nm, in contrast, the excitation leads to a manifold of higher excited states, Sn, that are primarily of Rydberg character. We are able to follow the gradual transition from the initially excited state to the dissociative receiver state in real time. The Rydberg states are intersected by a repulsive valence state that mediates a transition to the repulsive S2 surface. Therefore, we propose that the resulting diradical will eventually break apart on a longer timescale. The findings imply that upon going from UV−B to UV−C light the structural integrity of the disulfide moiety is compromised and proteins irradiated in this range will not be able to reform the initial tertiary structure, leading to loss of function.
High Exchange Rate Complexes of 129Xe with Water‐Soluble Pillar[5]arenes for Adjustable Magnetization Transfer MRI
Authors: Schnurr Matthias , Joseph Roymon , Naugolny‐Keisar Alissa , Kaizerman‐Kane Dana , Bogdanoff Nils , Schuenke Patrick , Cohen Yoram , Schröder Leif
Published: August 2018

Macrocyclic host structures for generating transiently bound 129Xe have been used in various ultra‐sensitive NMR and MRI applications for molecular sensing of biochemical analytes. They are based on hyperpolarized nuclei chemical exchange saturation transfer (Hyper‐CEST). Here, we tested a set of water‐soluble pillar[5]arenes with different counterions in order to compare their potential contrast agent abilities with that of cryptophane‐A (CrA), the most widely used host for such purposes. The exchange of Xe with such compounds was found to be sensitive to the type of ions present in solution and can be used for switchable magnetization transfer (MT) contrast that arises from off‐resonant pre‐saturation. We demonstrate that the adjustable MT magnitude depends on the interplay of saturation parameters and found that the optimum MT contrast surpasses the CrA CEST performance at moderate saturation power. Since modification of such water‐soluble pillar[5]arenes is straightforward, these compounds can be considered a promising platform for designing various sensors that may complement the field of Xe HyperCEST‐based biosensing MRI.
Tuning the Biradicaloid Nature of Polycyclic Aromatic Hydrocarbons: The Effect of Graphitic Nitrogen Doping in Zethrenes
Authors: Das Anita , Pinheiro Max , Machado Francisco B. C. , Aquino Adélia J. A. , Lischka Hans
Published: August 2018

Zethrenes are interesting polycyclic aromatic hydrocarbons (PAHs), which possess unique optoelectronic and magnetic properties because of their singlet open‐shell biradicaloid character, making them promising candidates for application in organic electronics. Tuning their properties is a key task in order to develop efficient compounds for practical use by balancing the desired biradicaloid character against its chemical instability. In this work, high‐level theoretical multireference methods appropriate for the correct description of polyradicaloid systems are used to develop rules for doping of zethrenes by means of nitrogen taking heptazethrene (HZ) as a benchmark example. The results of the quantum chemical calculations have been concentrated on a series of quantitative descriptors such as unpaired densities and singlet‐triplet (S−T) splittings. They clearly indicate different regions in the HZ where N‐doping can either lead to strong enhancement of the biradicaloid character or to strong quenching towards a closed shell state. A wide scale of varying open‐shell character is accessible from the different doping positions. It is shown that the S−T splittings correlate well with the total number of unpaired electrons in the medium range of biradicaloid character. For pronounced biradical character the S−T splitting decays to about zero with a margin of ±0.15 eV. In the opposite closed‐shell limit, much larger S−T splittings of up to 3 eV are computed.
Interpenetrating Polymer Network Microgels in Water: Effect of Composition on the Structural Properties and Electrosteric Interactions
Authors: Micali Norberto , Bertoldo Monica , Buratti Elena , Nigro Valentina , Angelini Roberta , Villari Valentina
Published: August 2018

Microgels of cross‐linked interpenetrating polymer networks (IPNs) are very versatile systems combining the properties of colloids and polymers. Herein we study IPN microgels composed of poly(N‐isopropylacrylamide) and poly(acrylic acid) to understand how weight composition and reactant concentrations affect their structural, conformational and electrosteric properties in water. The results show that it is possible to drive the formation of microgels with the desired properties by adjusting IPN composition and preparation method during the synthesis. During synthesis, the polymerization of acrylic acid triggers the merging among IPNs via covalent linking, giving rise to microgels with larger mass and size, the effect being larger for higher concentration of the reactants. In addition, a close relation between the microgel internal conformation and the colloidal stability is observed, due to the presence of screened groups inside the microgel.
Chemical Modification toward Long Spin Lifetimes in Organic Conjugated Radicals
Authors: Dai Ya‐Zhong , Dong Bo‐Wei , Kao Yi , Wang Zi‐Yuan , Un Hio‐Ieng , Liu Zheng , Lin Zhi‐Jun , Li Liang , Xie Fang‐Bai , Lu Yang , Xu Mei‐Xing , Lei Ting , Sun Yu‐Jie , Wang Jie‐Yu , Gao Song , Jiang Shang‐Da , Pei Jian
Published: August 2018

Organic semiconductors for spin‐based devices require long spin relaxation times. Understanding their spin relaxation mechanisms is critical to organic spintronic devices and applications for quantum information processing. However, reports on the spin relaxation mechanisms of organic conjugated molecules are rare and the research methods are also limited. Herein, we study the molecular design and spin relaxation mechanisms by systematically varying the structure of a conjugated radical. We found that solid‐state relaxation times of organic materials are largely different from that in solution state. We demonstrate that substitution of a lower gyromagnetic ratio nucleus (e. g. D, Cl) on the para‐position of the aryl rings in the triphenylmethyl (TM) radical can significantly improve their coherence times (Tm). Flexible thin films based on such radicals exhibit ultra‐long spin–lattice relaxation times (T1) up to 35.6(6) μs and Tm up to 1.08(4) μs under ambient conditions, which are among the longest values in films. More importantly, using the TM radical derivative (5CM), we observed room‐temperature quantum coherence and Rabi cycles in thin film for the first time, suggesting that organic conjugated radicals have great potentials for spin‐based information processing.
Two‐Photon Absorption Properties and Structures of BODIPY and Its Dyad, Triad and Tetrad
Authors: Yang Jian , Rousselin Yoann , Bucher Léo , Desbois Nicolas , Bolze Frédéric , Xu Hai‐Jun , Gros Claude P.
Published: August 2018

A series consisting of a dyad, a triad and a tetrad containing either two, three and four BODIPY units, respectively, has been synthesized and fully characterized and compared to two mono‐BODIPY analogs (used as references). The one‐ and two‐photon photophysical properties have been measured and the X‐ray structures of four of the BODIPY derivatives have been determined. In the 700–900 nm range, the two‐photon absorption (TPA) cross sections range from 30 GM to 160 GM for these compounds.
Spontaneous Formation of Nanochains from Triangular Silver Nanoplates
Authors: Zhao Jingru , Yang Ming
Published: August 2018

Self‐assembly represents an energy‐efficient way toward the configurable design of functional nanomaterials. In this paper, triangular silver nanoplates are shown to spontaneously form anisotropic assemblies in the solution. Nanochains consisting of face‐to‐face aligned nanoplates can reach hundreds of nanometers long after the dispersion of triangular silver nanoplates is allowed to age at room temperature for 1 week. The preferred face‐to‐face attachment is attributed to the maximized van der Waals attraction for a thermodynamically stable configuration as opposed to side‐by‐side attachment. Time‐dependent UV–vis spectra show a gradual blue‐shift along with the increase of aging time, indicating a likely stepwise growth of nanochains. The peak shift is however found to be much smaller than the results of finite‐difference time‐domain simulations based on the same sized nanoplates with ideally concentric face‐to‐face placement. Such discrepancy may be attributed to the possible misalignment and size variations of stacking nanoplates.
Ligand‐Free Bioinspired Suzuki–Miyaura Coupling Reactions using Aryltrifluoroborates as Effective Partners in Deep Eutectic Solvents
Authors: Dilauro Giuseppe , García Sergio Mata , Tagarelli Donato , Vitale Paola , Perna Filippo M. , Capriati Vito
Published: August 2018

Pd‐catalyzed Suzuki–Miyaura cross‐coupling between (hetero)aryl halides (Cl, Br, I) and versatile, moisture‐stable mono‐ and bifunctional potassium aryltrifluoroborates proceeded efficiently and chemoselectively in air and under generally mild conditions; a catalyst loading as low as 1 mol % combined with Na2CO3 as a base in choline chloride/glycerol (1:2) deep eutectic solvent (DES) was used as a sustainable and environmentally responsible medium. The catalyst, base, and DES were easily and successfully recycled up to six times with an E‐factor as low as 8.74. Valuable biaryls and terphenyl derivatives were furnished in yields of up to 98 %; over 50 reactions were compared and discussed. The methodology was applied for the synthesis of the nonsteroidal anti‐inflammatory drugs Felbinac and Diflunisal.
Key Single‐Atom Electrocatalysis in Metal—Organic Framework (MOF)‐Derived Bifunctional Catalysts
Authors: Zhao Wanpeng , Wan Gang , Peng Chunlei , Sheng Huaping , Wen Jianguo , Chen Hangrong
Published: August 2018

Metal–organic framework (MOF)‐derived materials have attracted increasing interest and show promising catalytic performances in many fields. Intensive efforts have been focused on the structure design and metal‐site integration in MOF‐derived catalysts. However, the key catalytic processes related with the metal sites in MOF‐derived catalysts that dominate the electrocatalytic performance still remain obscure. Herein, we show a neglected but critical issue in the pyrolytic synthesis of MOF‐derived catalysts: the coupled evolution of dual sites, that is, metallic sites and single‐atom metal sites. The identification of active sites of single‐atom sites from the visible particles has been elucidated through the combined X‐ray spectroscopic, electron microscopic, and electrochemical studies. Interestingly, after a total removal of metallic cobalt sites, catalysts with purified single‐atom metal sites show no faltering activity for either the oxygen reduction reaction (ORR) or hydrogen evolution reaction (HER), while significantly enhanced ORR selectivity is achieved; this reveals the dominant activity and selectivity contribution from single‐atom electrocatalysis. The insight of the coupled evolution of dual sites and the as‐demonstrated dual‐site decoupling strategies open up a new routine for the design and synthesis of MOF‐derived catalysts with the optimized single‐atom electrocatalysis towards various electrochemical reactions.
Towards Sustainable High‐Performance Thermoplastics: Synthesis, Characterization, and Enzymatic Hydrolysis of Bisguaiacol‐Based Polyesters
Authors: Curia Silvio , Biundo Antonino , Fischer Isabel , Braunschmid Verena , Gübitz Georg M. , Stanzione Joseph F.
Published: August 2018

Invited for this month's cover is the group of Joseph Stanzione at Rowan University. The Cover Image is an artistic photography effort aiming to show that lignin‐derived compounds can be utilized for the preparation of sustainable, highperformance polyesters susceptible to biodegradation. The Full Paper itself is available at 10.1002/cssc.201801059.
ClearCell® FX, a label‐free microfluidics technology for enrichment of viable circulating tumor cells
Authors: Lee Yifang , Guan Guofeng , Bhagat Ali Asgar
Published: August 2018

Circulating tumor cells (CTCs) dissociate from primary tumor into the bloodstream, and carry with them cancer's fingerprints as well as the potential to turn aggressive and metastasize. In order to understand CTCs and develop clinical utility, different methods of enrichment and isolation of CTCs can be used. Here, we report the use of a label‐free platform, ClearCell® FX which isolates CTCs by their mechanical features and its advantages. The technology utilizes Dean Flow Fractionation (DFF) principle in a spiral microfluidics system to separate the larger CTCs from smaller blood cells. The gentle and fast workflow allows for a range of downstream assays to be performed on the intact CTCs, particularly studies that examine an epithelial cell adhesion molecular (EpCAM)‐independent population. Viable, intact cells are also retrievable for development of culture or in vivo models. © 2018 International Society for Advancement of Cytometry
A rapid single cell sorting verification method using plate‐based image cytometry
Authors: Zigon Eric S. , Purseglove Suzanne M. , Toxavidis Vasilis , Rice William , Tigges John , Chan Leo Li‐Ying
Published: August 2018

Single cell sorting is commonly used for ensuring monoclonality and producing homogenous target cell populations. Current single cell verification methods involve manually confirming the existence of single cells or colonies in a well using a standard light microscope. However, the manual verification method is time‐consuming and highly tedious, which prompts a need for an accurate and rapid detection method for verifying single cell sorting capability. Here, we demonstrate a rapid single cell sorting verification method using the Celigo Image Cytometer. Calcein AM‐stained Jurkat cells and fluorescent beads are sorted into 96‐well half area microplates using the MoFlo Astrios EQ. Whole well bright field and fluorescent images are acquired and analyzed using the image cytometer in less than 8 min. The proposed single cell verification detection method in multi‐well microplates can allow for quick optimization of FACS instruments at flow core laboratories, as well as improvement of downstream biological assays by accurately confirming the presence of single cells in each well.
Navigating snowscapes: scale‐dependent responses of mountain sheep to snowpack properties
Authors: Mahoney Peter J. , Liston Glen E. , LaPoint Scott , Gurarie Eliezer , Mangipane Buck , Wells Adam G. , Brinkman Todd J. , Eitel Jan U. H. , Hebblewhite Mark , Nolin Anne W. , Boelman Natalie , Prugh Laura R.
Published: August 2018

Winters are limiting for many terrestrial animals due to energy deficits brought on by resource scarcity and the increased metabolic costs of thermoregulation and traveling through snow. A better understanding of how animals respond to snow conditions is needed to predict the impacts of climate change on wildlife. We compared the performance of remotely sensed and modeled snow products as predictors of winter movements at multiple spatial and temporal scales using a data set of 20,544 locations from 30 GPS‐collared Dall sheep (Ovis dalli dalli) in Lake Clark National Park and Preserve, Alaska, USA from 2005 to 2008. We used daily 500‐m MODIS normalized difference snow index (NDSI), and multi‐resolution snow depth and density outputs from a snowpack evolution model (SnowModel), as covariates in step selection functions. We predicted that modeled snow depth would perform best across all scales of selection due to more informative spatiotemporal variation and relevance to animal movement. Our results indicated that adding any of the evaluated snow metrics substantially improved model performance and helped characterize winter Dall sheep movements. As expected, SnowModel‐simulated snow depth outperformed NDSI at fine‐to‐moderate scales of selection (step scales < 112 h). At the finest scale, Dall sheep selected for snow depths below mean chest height (<54 cm) when in low‐density snows (100 kg/m3), which may have facilitated access to ground forage and reduced energy expenditure while traveling. However, sheep selected for higher snow densities (>300 kg/m3) at snow depths above chest height, which likely further reduced energy expenditure by limiting hoof penetration in deeper snows. At moderate‐to‐coarse scales (112–896 h step scales), however, NDSI was the best‐performing snow covariate. Thus, the use of publicly available, remotely sensed, snow cover products can substantially improve models of animal movement, particularly in cases where movement distances exceed the MODIS 500‐m grid threshold. However, remote sensing products may require substantial data thinning due to cloud cover, potentially limiting its power in cases where complex models are necessary. Snowpack evolution models such as SnowModel offer users increased flexibility at the expense of added complexity, but can provide critical insights into fine‐scale responses to rapidly changing snow properties.
Cryptic genetic variation and adaptation to waterlogging in Caledonian Scots pine, Pinus sylvestris L.
Authors: Donnelly Kevin , Cavers Stephen , Cottrell Joan E. , Ennos Richard A.
Published: August 2018

Local adaptation occurs as the result of differential selection among populations. Observations made under common environmental conditions may reveal phenotypic differences between populations with an underlying genetic basis; however, exposure to a contrasting novel environment can trigger release of otherwise unobservable (cryptic) genetic variation. We conducted a waterlogging experiment on a common garden trial of Scots pine, Pinus sylvestris (L.), saplings originating from across a steep rainfall gradient in Scotland. A flood treatment was maintained for approximately 1 year; physiological responses were gauged periodically in terms of photochemical capacity as measured via chlorophyll fluorescence. During the treatment, flooded individuals experienced a reduction in photochemical capacity, Fv/Fm, this reduction being greater for material originating from drier, eastern sites. Phenotypic variance was increased under flooding, and this increase was notably smaller in saplings originating from western sites where precipitation is substantially greater and waterlogging is more common. We conclude that local adaptation has occurred with respect to waterlogging tolerance and that, under the flooding treatment, the greater increase in variability observed in populations originating from drier sites is likely to reflect a relative absence of past selection. In view of a changing climate, we note that comparatively maladapted populations may possess considerable adaptive potential, due to cryptic genetic variation, that should not be overlooked.
Parasitic versus nutritional regulation of natural fish populations
Authors: Frantz Amélie , Perga Marie‐Elodie , Guillard Jean
Published: August 2018

Although parasites are expected to affect their host's fitness, quantitative proof for impacts of parasitism on wild populations is hampered by confounding environmental factors, including dietary resource. Herein, we evaluate whether the physiological conditions of European perch (Perca fluviatilis) in three large peri‐alpine lakes (Geneva, Annecy, and Bourget) depend on (a) the nutritional status of the juvenile fish, as revealed by stable isotope and fatty acid compositions, (b) the prevalence of the tapeworm Triaenophorus nodulosus, a parasite transmitted to perch through copepod preys, or (c) interactive effects of both factors. At the scale of lake populations, the deficit in growth and fat storage of juvenile perch during their first summer coincides with a high parasite prevalence and also a low quality of dietary resource. Yet, at the individual level, parasites had no evident effect on the growth of the juvenile perch, while impacts on fat storage appeared only at the highest prevalence of the most infected lake. Fatty acid and stable isotope analyses of fish tissue do not reveal any impact of T. nodulosus on diet, physiology, and feeding behaviour of fish within lakes. Overall, we found a low impact of parasitism on the physiological condition and trophic status of juvenile perch at the end of their first summer. We find instead that juvenile perch growth and fat storage, both factors tied to their winter survival, are under strong nutritional constraints. However, the coinciding nutritional constraints and parasite prevalence of perch juveniles in these three lakes may result from the indirect effect of lake nutrient concentrations, which, as a major control of zooplankton communities, simultaneously regulate both the dietary quality of fish prey and the host–parasite encounter rates.
Reduced representation sequencing detects only subtle regional structure in a heavily exploited and rapidly recolonizing marine mammal species
Authors: Dussex Nicolas , Taylor Helen R. , Stovall Willam R. , Rutherford Kim , Dodds Ken G. , Clarke Shannon M. , Gemmell Neil J.
Published: August 2018

Next‐generation reduced representation sequencing (RRS) approaches show great potential for resolving the structure of wild populations. However, the population structure of species that have shown rapid demographic recovery following severe population bottlenecks may still prove difficult to resolve due to high gene flow between subpopulations. Here, we tested the effectiveness of theRRSmethod Genotyping‐By‐Sequencing (GBS) for describing the population structure of the New Zealand fur seal (NZFS,Arctocephalus forsteri), a species that was heavily exploited by the 19th century commercial sealing industry and has since rapidly recolonized most of its former range from a few isolated colonies. Using 26,026 neutral single nucleotide polymorphisms (SNPs), we assessed genetic variation within and betweenNZFScolonies. We identified low levels of population differentiation across the species range (<1% of variation explained by regional differences) suggesting a state of near panmixia. Nonetheless, we observed subtle population substructure between West Coast and Southern East Coast colonies and a weak, but significant (p = 0.01), isolation‐by‐distance pattern among the eight colonies studied. Furthermore, our demographic reconstructions supported severe bottlenecks with potential 10‐fold and 250‐fold declines in response to Polynesian and European hunting, respectively. Finally, we were able to assign individuals treated as unknowns to their regions of origin with high confidence (96%) using ourSNPdata. Our results indicate that while it may be difficult to detect population structure in species that have experienced rapid recovery, next‐generation markers and methods are powerful tools for resolving fine‐scale structure and informing conservation and management efforts.
Linking geomorphic change due to floods to spatial hydraulic habitat dynamics
Authors: Tamminga Aaron , Eaton Brett
Published: August 2018

Large flood events have the capacity to induce geomorphic restructuring that can impact riverine ecosystems. However, the detailed morphodynamics associated with infrequent, high‐magnitude floods are variable and difficult to capture, and more research is needed into potential relationships between geomorphic change, flow organization, and aquatic habitat dynamics. In this study, we focus on the reach‐scale response of a gravel bed river to a large flood, employing a combined remote sensing, field measurement, and numerical modelling approach to measure and interpret conditions bracketing the flood. Documented geomorphic turnover was extensive, reworking low‐flow channel patterns and causing widespread bank erosion and sediment deposition. This resulted in a shift to wide, shallow flow conditions in the post‐flood morphology and a loss of hydraulic diversity, particularly in ecologically important pool and riffle units identified using a fuzzy statistical classification method. These impacts are most evident at low flows; higher discharges display relatively similar hydraulic conditions despite geomorphic change. Smaller‐scale adjustments in the year following the flood appear to be driving the reintroduction of hydraulic diversity, which is interpreted as beneficial for in‐stream brown trout. Results from this study highlight the utility of applying flexible and objective remote sensing and modelling methods to measure fluvial change and provide a real‐world example that can inform broader theoretical understanding of large flood ecohydrology.
Spatial heterogeneity in the abundance and fecundity of Arctic mosquitoes
Authors: Culler Lauren E. , Ayres Matthew P. , Virginia Ross A.
Published: August 2018

The abundance of mosquitoes is strongly influenced by biotic and abiotic factors that act on the immature (aquatic) and adult (terrestrial) life stages. Rapid changes in land use and climate, which impact aquatic and terrestrial mosquito habitat, necessitate studying the ecological mechanisms, and their interplay with the changing environment, that affect mosquito abundance. These data are crucial for anticipating how environmental change will impact their roles as pests, disease vectors, and in food webs. We studied a population of Arctic mosquitoes (Aedes nigripes, Diptera: Culicidae) in western Greenland, a region experiencing rapid environmental change, to quantify spatial variation in adult abundance and reproduction. Using sweep nets, we collected about sevenfold more mosquitoes within the town of Kangerlussuaq and within a low‐elevation tundra valley compared to three other tundra locations. Dissections of adult female mosquitoes revealed that only 17% were gravid overall, with a range of 7–43% among sites. If gravid, mosquitoes matured an average of 60 eggs per individual—more in larger females. We found no indication of autogenous egg development. Analyses using our field data indicated that spatial variation in adult fecundity and survival of immatures could each account for a 10‐fold range in the per capita growth of mosquito populations. The availability of vertebrate hosts and aquatic habitat is changing in many parts of the Arctic and can be expected to influence Arctic mosquito abundance. In the Arctic, and elsewhere, life‐history data from natural populations of mosquitoes will significantly aid in understanding controls on the abundance of these globally ubiquitous insects.
Dormancy‐defense syndromes and tradeoffs between physical and chemical defenses in seeds of pioneer species
Authors: Zalamea Paul‐Camilo , Dalling James W. , Sarmiento Carolina , Arnold A. Elizabeth , Delevich Carolyn , Berhow Mark A. , Ndobegang Anyangatia , Gripenberg Sofia , Davis Adam S.
Published: August 2018

Seeds of tropical pioneer trees have chemical and physical characteristics that determine their capacity to persist in the soil seed bank. These traits allow seeds to survive in the soil despite diverse predators and pathogens, and to germinate and recruit even decades after dispersal. Defenses in seedlings and adult plants often are described in terms of tradeoffs between chemical and physical defense, but the interplay of defensive strategies has been evaluated only rarely for seeds. Here we evaluated whether classes of seed defenses were negatively correlated across species (consistent with tradeoffs in defense strategies), or whether groups of traits formed associations across species (consistent with seed defense syndromes). Using 16 of the most common pioneer tree species in a neotropical lowland forest in Panama we investigated relationships among four physical traits (seed fracture resistance, seed coat thickness, seed permeability, and seed mass) and two chemical traits (number of phenolic compounds and phenolic peak area), and their association with seed persistence. In addition, seed toxicity was assessed with bioassays in which we evaluated the activity of seed extracts against representative fungal pathogens and a model invertebrate. We did not find univariate tradeoffs between chemical and physical defenses. Instead, we found that seed permeability – a trait that distinguishes physical dormancy from other dormancy types – was positively associated with chemical defense traits and negatively associated with physical defense traits. Using a linear discriminant analysis and a hierarchical cluster analysis we found evidence to distinguish three distinct seed defense syndromes that correspond directly with seed dormancy classes (i.e., quiescent, physical, and physiological). Our data suggest that short and long‐term persistence of seeds can be achieved via two strategies: having permeable seeds that are well defended chemically, corresponding to the physiologically dormant defense syndrome; or having impermeable seeds that are well defended physically, corresponding to the physically dormant defense syndrome. In turn, transient seeds appear to have a lower degree of chemical and physical defenses, corresponding to the quiescent defense syndrome. Overall, we find that seed defense and seed dormancy are linked, suggesting that environmental pressures on seed persistence and for delayed germination can select for trait combinations defining distinct dormancy‐defense syndromes.
Competition for microsites during recruitment in semiarid annual plant communities
Authors: Boeken Bertrand R.
Published: August 2018

The concept of microsites for recruitment is central to plant ecology, but it is unclear whether these sites are abstract constructs or real entities. I hypothesize that, in generally microsite‐limited communities, microsites comprise a limiting physical resource for which different species compete. I tested this hypothesis on winter‐annual communities on biocrust in the semiarid Northern Negev of Israel, in which most species are microsite‐limited, while the dominant grass (Stipa capensis) has overcome this limitation by efficient microsite acquisition and a lack of secondary seed dormancy. I tested whether the dominant suppresses the subordinate species, collectively, during recruitment, rather than during growth. To this end, I conducted a field experiment with three blocks of six plots (6 m × 6 m) with two treatments – mowing in spring 2006 (intershrub, intershrub + shrub patches, and none) and shrub‐patch removal (0% or 50% of the patches). I collected data from four seed traps per plot before spring 2007 and from five plant samples per plot at the end of spring. Mowing significantly reduced both seed and plant density of the dominant species, reflecting seed‐limited recruitment, and increased subordinate plant density by competitive release. Multiple regressions of per‐plant and per‐gram effects and responses showed that competition was a direct effect of the dominant's density. Total and per‐group biomass was proportional to density, implying density‐independent per capita growth. Subordinate species number also increased with their density, due to the sample‐size effect. These findings indicate that the seed‐limited dominant diffusely suppresses the subordinates during recruitment, supporting the microsite competition hypothesis. The shift from growth resources to microsites extends the role of inter‐specific competition along productivity and disturbance gradients, and highlights the asymmetric relationship between the two kinds of competition, as microsite competition is only observable if initial abundances are not overshadowed by density‐dependent growth and mortality. The findings also demonstrate that (1) lacking secondary seed dormancy is an evolutionarily stable strategy in dryland annuals, alongside seed dormancy in microsite‐limited species, and (2) biomass removal (e.g., by herbivory) increases small‐scale biodiversity, enhancing the sustainability of dryland grazing, but without compensatory growth.
A Supramolecular Gel Based on 12‐Hydroxystearic Acid/Virgin Coconut Oil for Injectable Drug Delivery
Authors: Tantishaiyakul Vimon , Ouiyangkul Passaporn , Wajasat Makawan , Pawisat Tasana , Hirun Namon , Sangfai Tanatchaporn
Published: August 2018

A supramolecular organogel based on 3 wt% of 12‐hydroxystearic acid (HSA) and virgin coconut oil (oil) in the presence of a gel inhibitor, 4 wt% ethanol (EtOH), is developed and investigated for injectable implant delivery. Gel formation is observed by the test tube tilting method. The characteristic properties of the sol‐gel system are determined using rheological, thermal, and turbidity analyses. The in vitro releases of piroxicam (PX) and diclofenac acid (DFA), the models for hydrophilic and lipophilic drugs, respectively, are performed. Characterization of the blends from the three methods are comparable and indicate that the systems of HSA/oil, PX/HSA/oil, and DFA/HSA/oil gel at about 36–39 °C upon cooling and the gel turns to a sol at a temperature higher than 50 °C upon heating at a rate of 2 °C min−1. Isothermal measurements reveals that HSA/EtOH/oil, PX/HSA/EtOH/oil, and DFA/HSA/EtOH/oil remain as a sol for about 18 min at room temperature (25 °C). Both PX and DFA show a sustained release from HSA/oil and HSA/EtOH/oil.

Practical Applications: The presence of ethanol which is a hydrophilic molecule can disrupt the interaction between HSA molecules and suppress gel formation at the low temperature that the system normally forms gel. This HSA/EtOH/oil system might be injectable at room temperature and become gels at the site of injection when EtOH is diffused to other tissues in the body. This system is beneficial for use as an injectable implant system for a sustained delivery of both hydrophilic and hydrophobic drugs.

12‐hydroxystearic acid (HSA) and virgin coconut oil (oil) can form gels at body and lower temperatures e.g., room temperatures. The sol‐gel system is characterized using rheological, thermal, and turbidity methods. Ethanol inhibits gel formation at room temperature to facilitate injection. The mixture of HSA, ethanol, and oil might be used as an injectable implantation. Two hydrophobic (diclofenac) and hydrophilic (piroxicam) model drugs show sustained releases from HSA/oil and HSA/ethanol/oil.
Concentration of Gamma‐Linolenic and Stearidonic Acids as Free Fatty Acids and Ethyl Esters from Viper's Bugloss Seed Oil by Urea Complexation
Authors: Rincón‐Cervera Miguel Ángel , Galleguillos‐Fernández Raúl , González‐Barriga Valeria , Valenzuela Rodrigo , Valenzuela Alfonso
Published: August 2018

In this work, gamma‐linolenic acid (GLA) and stearidonic acid (SDA) are successfully concentrated as free fatty acids (FFA) and ethyl esters (EE) using the urea complexation method at room temperature and two sources of these fatty acids: commercial Echium plantagineum seed oil as well as extracted oil from this species which is grown in Chile. Concentration factors (% fatty acid in the concentrate/% fatty acid in the original oil) for both fatty acids are found to be between 2.35 and 2.65, although they are more efficiently concentrated as FFA than as EE using both commercial and extracted oils. This is the first work which reports the use of Echium plantagineum seed oil from Chilean origin to produce GLA and SDA concentrates as FFA and EE, with similar results that those obtained with commercial Echium oil.

Practical Applications: The interest for GLA and SDA as functional ingredients is increasing in the last few years because of their beneficial effects for human health and their plant origin, as they are mainly provided by seed oils from some Boraginaceae species. In this work, GLA and SDA are selectively concentrated from the rest of fatty acids contained in Echium seed oil by the urea method at room temperature, which is a cheap, safe, and easily scalable process. These concentrates, especially as FFA because of their nutritional characteristics versus EE, may become high added‐value ingredients to be incorporated to functional oils or even substrates for the enzymatic synthesis of structured lipids providing GLA and SDA with a higher bioefficiency than currently available oils.

Operational scheme developed in this work which consists of: 1) derivatization of Echium plantagineum oil from two origins (extracted from Chilean seeds and commercial oil) to free fatty acids (FFA) and ethyl esters (EE) and 2) processing of FFA and EE by urea at room temperature to concentrate GLA and SDA.