bluuebunny/crossref_metadata_2025 huggingface dataset:
Field Observations and Physical‐Biogeochemical Modeling Suggest Low Silicon Affinity for Antarctic Fast Ice Diatoms
Authors: Lim S. M. , Moreau S. , Vancoppenolle M. , Deman F. , Roukaerts A. , Meiners K. M. , Janssens J. , Lannuzel D.
Published: September 2019

We use field observations from late spring and a one‐dimensional sea‐ice model to explore a high nutrient, high chlorophyll system in Antarctic land‐fast ice. Lack of variability in chlorophyll a concentration and organic carbon content over the 17‐day sampling period suggests a balance between macronutrient sources and biological uptake. Nitrate, nitrite, phosphate, and ammonium were measured at concentrations well above salinity‐predicted levels, indicating nutrient accumulation fueled by remineralization processes. However, silicic acid (DSi) was depleted relative to seawater and was potentially limiting. One‐dimensional physical‐biogeochemical sea‐ice model simulations at the observation site achieve extremely high algal growth and DSi uptake with a DSi half‐saturation constant used for pelagic diatoms (KSi = 3.9 μM) and are not sufficiently improved by tuning the DSi:carbon ratio or DSi remineralization rate. In contrast, diatom biomass in the bottom ice, which makes up 70% of the observed chlorophyll, is simulated using KSi an order of magnitude higher (50 μM), a value similar to that measured in a few Antarctic diatom cultures. Some sea‐ice diatoms may therefore experience limitation at relatively high ambient DSi concentrations compared to pelagic diatoms. Our study highlights the urgent need for observational data on sea‐ice algal affinity for DSi to further support this hypothesis. A lower algal growth rate increases model predictions of DSi in the upper sea ice to more accurate concentrations. The model currently does not account for the non‐diatom communities that dominate those layers, and thus, modeling diatom communities overpredicts DSi uptake in the upper ice.
Continental‐Scale Landscape Evolution: A History of North American Topography
Authors: Fernandes Victoria M. , Roberts Gareth G. , White Nicky , Whittaker Alexander C.
Published: September 2019

The generation and evolution of continental topography are fundamental geologic and geomorphic concerns. In particular, the history of landscape development might contain useful information about the spatiotemporal evolution of deep Earth processes, such as mantle convection. A significant challenge is to generate observations and theoretical predictions of sufficient fidelity to enable landscape evolution to be constrained at scales of interest. Here, we combine substantial inventories of stratigraphic and geomorphic observations with inverse and forward modeling approaches to determine how the North American landscape evolved. First, stratigraphic markers are used to estimate postdepositional regional uplift. Present‐day elevations of these deposits demonstrate that >2 km of long‐wavelength surface uplift centered on the Colorado‐Rocky‐Mountain plateaus occurred in Cenozoic times. Second, to bridge the gaps between these measurements, an inverse modeling scheme is used to calculate the smoothest spatiotemporal pattern of rock uplift rate that yields the smallest misfit between 4,161 observed and calculated longitudinal river profiles. Our results suggest that Cenozoic regional uplift occurred in a series of stages, in agreement with independent stratigraphic observations. Finally, a landscape evolution model driven by this calculated rock uplift history is used to determine drainage patterns, denudation, and sedimentary flux from Late Cretaceous times until the present day. These patterns are broadly consistent with stratigraphic and thermochronologic observations. We conclude that a calibrated inverse modeling strategy can be used to reliably extract the temporal and spatial evolution of the North American landscape at geodynamically useful scales.
Scientists Praise Urgency, Aggressive Plans in Climate Town Hall
Authors: Duncombe Jenessa , Cartier Kimberly
Published: September 2019

Democratic candidates detailed their plans to address the “existential crisis” of our time. Climate scientists were happy to have a forum—and happier that it was substantive.
The Solar Clock
Authors: Russell C.T. , Jian L.K. , Luhmann J.G.
Published: September 2019

The Sun is powered by a very stable source of fusion energy in its core that radiates that energy outward in a constant flow. Yet it has a cycle of magnetic dynamo activity whose strength and duration are variable. This variability, which affects the Earth's “space climate,” points to temporal changes in the convective and diffusive transport of magnetic flux above the tachocline, where the flux is generated. The longest record we have of this variability is the time series of sunspot numbers. This record suggests that the interior of the Sun follows a clock‐like magnetic flux production cycle with a length of close to 11.05 years. The variations in sunspot cycle duration, as well as the sunspot number rise and fall times, their hemispheric asymmetries, and the maximum sunspot numbers of the individual cycles are likely produced in the process of the magnetic flux transport. Helioseismology continues to shed more light on the convection zone variabilities, including the “torsional oscillations” that seem to have a special connection to the emerging strong magnetic fluxes that produce the sunspots. These new observations may eventually lead to an explanation for the surprisingly good correlation between the rate of sunspot appearance and the maximum sunspot number and to a better understanding of the relationship between the solar dynamo and the sunspot number cycle. Better understanding of the polar regions awaits long‐term monitoring with a polar solar mission. Better predictions of near‐term space weather could be obtained from a permanent L5 monitor.
PDD_GBR: Research on Evaporation Duct Height Prediction Based on Gradient Boosting Regression Algorithm
Authors: Zhao Wenpeng , Li Jincai , Zhao Jun , Zhao Dandan , Zhu Xiaoyu
Published: September 2019

Evaporation duct is a special atmospheric stratification that always exists at sea, which has an important influence on electromagnetic wave propagation. Accurate prediction of evaporation duct height is of great significance for radio information system. In the era of big data, machine learning has been widely used in various research work and achieved a series of excellent results. Based on the observation data method, this paper studies the prediction model using Gradient Boosting Regression algorithm (GBR) and proposes the pure data‐driven GBR (PDD_GBR), GBR_Paulus‐Jeske (GBR_PJ), and GBR_Babin‐Young‐Carton (GBR_BYC) evaporation duct prediction models. Simultaneously, traditional Paulus‐Jeske (PJ) model, Babin‐Young‐Carton (BYC) model, and existing SVR_PJ model are introduced into the experiment to make a comparison. The comprehensive performance of PDD_GBR model is optimal among these models with high stability and strong generalization ability, whose prediction accuracy has a great promotion compared with other models.
Exploring the Gender Development Histories of Children and Adolescents Presenting for Gender Affirming Medical Care
Authors: Kuper Laura E. , Lindley Louis , Lopez Ximena
Published: September 2019

Objective: The present study descriptively explores the childhood experiences, social transition and disclosure milestones and trajectories, reactions to disclosure, gender affirmation at school, dissatisfaction with sex characteristics, and desires for gender affirming medical care (GAMC) within a sample of transgender children and adolescents presenting for GAMC. Method: Participants were children and adolescents ( N = 224; Age 6–17 years) who participated in an initial assessment at a multidisciplinary gender affirming program in Dallas, Texas. Data were extracted from assessment notes and participants also completed self-report measures of current depression, anxiety, and body-related dissatisfaction. Results: Most participants reported awareness of their gender identity in childhood or early adolescence and started to take steps in social transition and disclosure during adolescence, prior to presenting for GAMC. However, these milestones were not confined to 1 developmental period, and the specific progression of milestones, degree of dissatisfaction with sex characteristics, and desires for GAMC beyond feminizing/masculinizing hormone therapy were diverse. Gender differences were found in milestones, requests to change name and pronoun at school, dissatisfaction with sex characteristics, and GAMC desires. Dissatisfaction with body shape and voice were associated with greater symptoms of depression. Somewhat surprisingly, most participants did not report any distressing reactions to disclosure (63.6%). However, most were not able to use the bathroom associated with their affirmed gender at school. Conclusions: Clinical approaches sensitive to the diversity of developmental contexts, identities, and desires for GAMC are needed.

Implications for Impact Statement

By descriptively exploring the gender development histories of transgender children and adolescents presenting for gender affirming medical care, the present study assists providers in anticipating the trajectories and associated needs of this rapidly growing population.
Psychological Functioning, Parenting Stress, and Parental Support Among Clinic-Referred Prepubertal Gender-Expansive Children
Authors: Kolbuck Victoria D. , Muldoon Abigail L. , Rychlik Karen , Hidalgo Marco A. , Chen Diane
Published: September 2019

Objective: The purpose of this study was to describe psychological functioning, parenting stress, and parental support of gender expansiveness in prepubertal gender-expansive children presenting to a specialized pediatric gender clinic and to examine relations between parenting factors and child psychological functioning. Method: Standard-of-care questionnaires were completed by parents of all children presenting for services. Data from prepubertal children (i.e., Tanner Stage 1 of pubertal development) seen between August 2013 and April 2018 were extracted from patient charts. Results: Data were analyzed from 71 youth ages 3–11, including 20% ( n = 14) ages 5 and younger. Fourteen percent of the sample ( n = 10) met diagnostic cutoff criteria for generalized anxiety disorder, and 20% ( n = 14) for oppositional defiant disorder. Caregivers reported varying levels of support of their child’s gender expansiveness (female caregivers: M = 78.85, SD = 8.68, range = 56–90; male caregivers: M = 77.32, SD = 10.37, range = 53–90), and only 3% ( n = 2) of caregivers endorsed parenting stress levels in the high range. Parenting stress significantly predicted higher symptom counts across all 8 diagnoses. Unexpectedly, higher levels of parental support predicted more symptoms of major depressive disorder and dysthymia. Parenting stress was a significant moderator of relations between gender nonconformity and attention-deficit/hyperactivity disorder (ADHD) hyperactive–impulsive type and conduct disorder symptoms; higher levels of gender nonconformity were associated with higher symptom counts at moderate and high levels of parenting stress (but not at low levels of parenting stress). Conclusions: Clinical interventions aimed at reducing parenting stress among caregivers of gender-expansive children may have a positive effect on children’s psychological functioning.

Implications for Impact Statement

Higher levels of gender nonconformity were associated with more attention-deficit/hyperactivity disorder (ADHD) hyperactive–impulsive type and conduct disorder symptoms but only at moderate or high (not low) levels of parenting stress. Thus, interventions aimed at reducing parenting stress in caregivers of gender-expansive children may improve children’s psychological functioning.
Childhood Social Gender Transition and Psychosocial Well-Being: A Comparison to Cisgender Gender-Variant Children
Authors: Wong Wang Ivy , van der Miesen Anna I. R. , Li Tjonnie G. F. , MacMullin Laura N. , VanderLaan Doug P.
Published: September 2019

Objective: There is increasing interest regarding best practice for promoting well-being among gender-variant children. Social gender transition (e.g., name, pronoun, clothing changes) may benefit gender-variant children who desire to be of a gender that does not align with their birth-assigned sex. This study examined psychosocial challenges experienced by socially transitioned children and cisgender (i.e., birth-assigned sex and gender identity align) gender-variant children. Method: We used data from published samples of gender-variant children ( N = 266) reporting psychosocial well-being using the Child Behavior Checklist or similar measures. A statistical bootstrapping approach was used to control for birth-assigned sex, age, and degree of gender variance when comparing cisgender gender-variant (CGV) and socially transitioned children described as being supported in their gender identities. Within the CGV sample, we examined parental attitudes toward childhood gender variance, as well as correlations between these parental attitudes and peer relations with children’s psychological well-being. Results: There was little evidence that psychosocial well-being varied in relation to gender transition status. Parents of CGV children were generally accepting of childhood gender variance, but only poor peer relations predicted lower psychological well-being among these children. Conclusion: Socially transitioned children appear to experience similar levels of psychosocial challenges as CGV children. While further research is needed to evaluate possible effects of childhood social gender transition on well-being, this study suggests experiences of psychosocial challenges among gender-variant children require monitoring irrespective of transition status, and relationships with peers may be especially important to consider.

Implications for Impact Statement

In general, gender-“atypical” children experience more risk of psychosocial challenges, and addressing poor peer relations may be key for ameliorating these risks.
Adherence Knowledge and Education Needs Among Pediatric Psychology Trainees: A Needs Assessment and Recommendations
Authors: Psihogios Alexandra M. , Gutiérrez-Colina Ana M. , Iskander Jeannette M. , Wasserman Rachel M. , Ramsey Rachelle R.
Published: September 2019

Objective: The purpose of this study was to assess pediatric psychology trainees’ perceived knowledge and understanding of clinical and ethical/professional issues in the area of treatment adherence. A secondary goal was to determine trainees’ needs and preferences for additional adherence-related training. Method: Seventy-nine trainees consisting of graduate students (49.4%), doctoral interns (20.2%), and postdoctoral fellows (30.4%) completed the Adherence Training Needs Assessment, a 26-item survey created by Adherence Special Interest Group leaders and approved by the Executive Board of the Society of Pediatric Psychology. This survey assessed trainee’s experiences, perceived competencies, training barriers, and desire and recommendations for additional training in the areas of adherence assessment, intervention, and ethical and professional issues. Results: Findings highlight adherence training gaps across several domains, notably evidence-based assessment, intervention, and theoretical knowledge. The vast majority of trainees endorsed a desire to enhance their adherence competencies through hands-on clinical training and increased access to adherence resources. Conclusions: To continue Society of Pediatric Psychology’s commitment to training pediatric psychologists, this paper highlights current challenges and novel opportunities to provide optimal adherence training.

Implications for Impact Statement

This study suggests that pediatric psychology trainees have unmet educational needs related to adherence and desire additional training in adherence assessment and intervention. Facilitating trainees’ education and training in adherence has important and widespread implications in ultimately addressing this prevalent clinical issue, advancing empirical knowledge, developing and implementing robust interventions, and collaborating with other providers to provide the best care to patients and families.
ALDH7A1 inhibits the intracellular transport pathways during hypoxia and starvation to promote cellular energy homeostasis
Authors: Yang Jia-Shu , Hsu Jia-Wei , Park Seung-Yeol , Lee Stella Y. , Li Jian , Bai Ming , Alves Claudia , Tseng William , Michelet Xavier , Ho I-Cheng , Hsu Victor W.
Published: September 2019

The aldehyde dehydrogenase (ALDH) family of metabolic enzymes converts aldehydes to carboxylates. Here, we find that the reductive consequence of ALDH7A1 activity, which generates NADH (nicotinamide adenine dinucleotide, reduced form) from NAD, underlies how ALDH7A1 coordinates a broad inhibition of the intracellular transport pathways. Studying vesicle formation by the Coat Protein I (COPI) complex, we elucidate that NADH generated by ALDH7A1 targets Brefeldin-A ADP-Ribosylated Substrate (BARS) to inhibit COPI vesicle fission. Moreover, defining a physiologic role for the broad transport inhibition exerted by ALDH7A1, we find that it acts to reduce energy consumption during hypoxia and starvation to promote cellular energy homeostasis. These findings advance the understanding of intracellular transport by revealing how the coordination of multiple pathways can be achieved, and also defining circumstances when such coordination is needed, as well as uncovering an unexpected way that NADH acts in cellular energetics.
Components of genetic associations across 2,138 phenotypes in the UK Biobank highlight adipocyte biology
Authors: Tanigawa Yosuke , Li Jiehan , Justesen Johanne M. , Horn Heiko , Aguirre Matthew , DeBoever Christopher , Chang Chris , Narasimhan Balasubramanian , Lage Kasper , Hastie Trevor , Park Chong Y. , Bejerano Gill , Ingelsson Erik , Rivas Manuel A.
Published: September 2019

Population-based biobanks with genomic and dense phenotype data provide opportunities for generating effective therapeutic hypotheses and understanding the genomic role in disease predisposition. To characterize latent components of genetic associations, we apply truncated singular value decomposition (DeGAs) to matrices of summary statistics derived from genome-wide association analyses across 2,138 phenotypes measured in 337,199 White British individuals in the UK Biobank study. We systematically identify key components of genetic associations and the contributions of variants, genes, and phenotypes to each component. As an illustration of the utility of the approach to inform downstream experiments, we report putative loss of function variants, rs114285050 (GPR151) and rs150090666 (PDE3B), that substantially contribute to obesity-related traits and experimentally demonstrate the role of these genes in adipocyte biology. Our approach to dissect components of genetic associations across the human phenome will accelerate biomedical hypothesis generation by providing insights on previously unexplored latent structures.
Human genome-edited hematopoietic stem cells phenotypically correct Mucopolysaccharidosis type I
Authors: Gomez-Ospina Natalia , Scharenberg Samantha G. , Mostrel Nathalie , Bak Rasmus O. , Mantri Sruthi , Quadros Rolen M. , Gurumurthy Channabasavaiah B. , Lee Ciaran , Bao Gang , Suarez Carlos J. , Khan Shaukat , Sawamoto Kazuki , Tomatsu Shunji , Raj Nitin , Attardi Laura D. , Aurelian Laure , Porteus Matthew H.
Published: September 2019

Lysosomal enzyme deficiencies comprise a large group of genetic disorders that generally lack effective treatments. A potential treatment approach is to engineer the patient’s own hematopoietic system to express high levels of the deficient enzyme, thereby correcting the biochemical defect and halting disease progression. Here, we present an efficient ex vivo genome editing approach using CRISPR-Cas9 that targets the lysosomal enzyme iduronidase to the CCR5 safe harbor locus in human CD34+ hematopoietic stem and progenitor cells. The modified cells secrete supra-endogenous enzyme levels, maintain long-term repopulation and multi-lineage differentiation potential, and can improve biochemical and phenotypic abnormalities in an immunocompromised mouse model of Mucopolysaccharidosis type I. These studies provide support for the development of genome-edited CD34+ hematopoietic stem and progenitor cells as a potential treatment for Mucopolysaccharidosis type I. The safe harbor approach constitutes a flexible platform for the expression of lysosomal enzymes making it applicable to other lysosomal storage disorders.
A bioinspired hydrogen bond-triggered ultrasensitive ionic mechanoreceptor skin
Authors: Amoli Vipin , Kim Joo Sung , Jee Eunsong , Chung Yoon Sun , Kim So Young , Koo Jehyoung , Choi Hanbin , Kim Yunah , Kim Do Hwan
Published: September 2019

Biological cellular structures have inspired many scientific disciplines to design synthetic structures that can mimic their functions. Here, we closely emulate biological cellular structures in a rationally designed synthetic multicellular hybrid ion pump, composed of hydrogen-bonded [EMIM+][TFSI−] ion pairs on the surface of silica microstructures (artificial mechanoreceptor cells) embedded into thermoplastic polyurethane elastomeric matrix (artificial extracellular matrix), to fabricate ionic mechanoreceptor skins. Ionic mechanoreceptors engage in hydrogen bond-triggered reversible pumping of ions under external stimulus. Our ionic mechanoreceptor skin is ultrasensitive (48.1–5.77 kPa−1) over a wide spectrum of pressures (0–135 kPa) at an ultra-low voltage (1 mV) and demonstrates the ability to surpass pressure-sensing capabilities of various natural skin mechanoreceptors (i.e., Merkel cells, Meissner’s corpuscles, Pacinian corpuscles). We demonstrate a wearable drone microcontroller by integrating our ionic skin sensor array and flexible printed circuit board, which can control directions and speed simultaneously and selectively in aerial drone flight.
Solvent-triggered reversible interconversion of all-nitrogen-donor-protected silver nanoclusters and their responsive optical properties
Authors: Yuan Shang-Fu , Guan Zong-Jie , Liu Wen-Di , Wang Quan-Ming
Published: September 2019

Surface organic ligands are critical in determining the formation and properties of atomically precise metal nanoclusters. In contrast to the conventionally used thiolate, phosphine and alkynyl ligands, the amine ligand dipyridylamine is applied here as a protecting agent in the synthesis of atomically precise metal nanoclusters. We report two homoleptic amido-protected Ag nanoclusters as examples of all-nitrogen-donor-protected metal nanoclusters: [Ag21(dpa)12]SbF6 (Ag21) and [Ag22(dpa)12](SbF6)2 (Ag22) (dpa = dipyridylamido). Single crystal X-ray structural analysis reveals that both clusters consist of a centered-icosahedron Ag13 core wrapped by 12 dpa ligands. The flexible arrangement of the N donors in dpa facilitates the solvent-triggered reversible interconversion between Ag21 and Ag22 due to their very different solubility. The successful use of dpa in the synthesis of well-defined silver nanoclusters may motivate more studies on metal nanoclusters protected by amido type ligands.
Balancing hydrogen adsorption/desorption by orbital modulation for efficient hydrogen evolution catalysis
Authors: Li Feng , Han Gao-Feng , Noh Hyuk-Jun , Jeon Jong-Pil , Ahmad Ishfaq , Chen Shanshan , Yang Changduk , Bu Yunfei , Fu Zhengping , Lu Yalin , Baek Jong-Beom
Published: September 2019

Hydrogen adsorption/desorption behavior plays a key role in hydrogen evolution reaction (HER) catalysis. The HER reaction rate is a trade-off between hydrogen adsorption and desorption on the catalyst surface. Herein, we report the rational balancing of hydrogen adsorption/desorption by orbital modulation using introduced environmental electronegative carbon/nitrogen (C/N) atoms. Theoretical calculations reveal that the empty d orbitals of iridium (Ir) sites can be reduced by interactions between the environmental electronegative C/N and Ir atoms. This balances the hydrogen adsorption/desorption around the Ir sites, accelerating the related HER process. Remarkably, by anchoring a small amount of Ir nanoparticles (7.16 wt%) in nitrogenated carbon matrixes, the resulting catalyst exhibits significantly enhanced HER performance. This includs the smallest reported overpotential at 10 mA cm−2 (4.5 mV), the highest mass activity at 10 mV (1.12 A mgIr−1) and turnover frequency at 25 mV (4.21 H2 s−1) by far, outperforming Ir nanoparticles and commercial Pt/C.
Production of zosteric acid and other sulfated phenolic biochemicals in microbial cell factories
Authors: Jendresen Christian Bille , Nielsen Alex Toftgaard
Published: September 2019

Biological production and application of a range of organic compounds is hindered by their limited solubility and toxicity. This work describes a process for functionalization of phenolic compounds that increases solubility and decreases toxicity. We achieve this by screening a wide range of sulfotransferases for their activity towards a range of compounds, including the antioxidant resveratrol. We demonstrate how to engineer cell factories for efficiently creating sulfate esters of phenolic compounds through the use of sulfotransferases and by optimization of sulfate uptake and sulfate nucleotide pathways leading to the 3′-phosphoadenosine 5′-phosphosulfate precursor (PAPS). As an example we produce the antifouling agent zosteric acid, which is the sulfate ester ofp-coumaric acid, reaching a titer of 5 g L−1in fed-batch fermentation. The described approach enables production of sulfate esters that are expected to provide new properties and functionalities to a wide range of application areas.
Spatially clustered loci with multiple enhancers are frequent targets of HIV-1 integration
Authors: Lucic Bojana , Chen Heng-Chang , Kuzman Maja , Zorita Eduard , Wegner Julia , Minneker Vera , Wang Wei , Fronza Raffaele , Laufs Stefanie , Schmidt Manfred , Stadhouders Ralph , Roukos Vassilis , Vlahovicek Kristian , Filion Guillaume J. , Lusic Marina
Published: September 2019

HIV-1 recurrently targets active genes and integrates in the proximity of the nuclear pore compartment in CD4+ T cells. However, the genomic features of these genes and the relevance of their transcriptional activity for HIV-1 integration have so far remained unclear. Here we show that recurrently targeted genes are proximal to super-enhancer genomic elements and that they cluster in specific spatial compartments of the T cell nucleus. We further show that these gene clusters acquire their location during the activation of T cells. The clustering of these genes along with their transcriptional activity are the major determinants of HIV-1 integration in T cells. Our results provide evidence of the relevance of the spatial compartmentalization of the genome for HIV-1 integration, thus further strengthening the role of nuclear architecture in viral infection.
Typhoid toxin exhausts the RPA response to DNA replication stress driving senescence and Salmonella infection
Authors: Ibler Angela E. M. , ElGhazaly Mohamed , Naylor Kathryn L. , Bulgakova Natalia A. , F. El-Khamisy Sherif , Humphreys Daniel
Published: September 2019

Salmonella Typhi activates the host DNA damage response through the typhoid toxin, facilitating typhoid symptoms and chronic infections. Here we reveal a non-canonical DNA damage response, which we call RING (response induced by a genotoxin), characterized by accumulation of phosphorylated histone H2AX (γH2AX) at the nuclear periphery. RING is the result of persistent DNA damage mediated by toxin nuclease activity and is characterized by hyperphosphorylation of RPA, a sensor of single-stranded DNA (ssDNA) and DNA replication stress. The toxin overloads the RPA pathway with ssDNA substrate, causing RPA exhaustion and senescence. Senescence is also induced by canonical γΗ2ΑΧ foci revealing distinct mechanisms. Senescence is transmitted to non-intoxicated bystander cells by an unidentified senescence-associated secreted factor that enhances Salmonella infections. Thus, our work uncovers a mechanism by which genotoxic Salmonella exhausts the RPA response by inducing ssDNA formation, driving host cell senescence and facilitating infection.
Ciliary exclusion of Polycystin-2 promotes kidney cystogenesis in an autosomal dominant polycystic kidney disease model
Authors: Walker Rebecca V. , Keynton Jennifer L. , Grimes Daniel T. , Sreekumar Vrinda , Williams Debbie J. , Esapa Chris , Wu Dongsheng , Knight Martin M. , Norris Dominic P.
Published: September 2019

The human PKD2 locus encodes Polycystin-2 (PC2), a TRPP channel that localises to several distinct cellular compartments, including the cilium. PKD2 mutations cause Autosomal Dominant Polycystic Kidney Disease (ADPKD) and affect many cellular pathways. Data underlining the importance of ciliary PC2 localisation in preventing PKD are limited because PC2 function is ablated throughout the cell in existing model systems. Here, we dissect the ciliary role of PC2 by analysing mice carrying a non-ciliary localising, yet channel-functional, PC2 mutation. Mutants develop embryonic renal cysts that appear indistinguishable from mice completely lacking PC2. Despite not entering the cilium in mutant cells, mutant PC2 accumulates at the ciliary base, forming a ring pattern consistent with distal appendage localisation. This suggests a two-step model of ciliary entry; PC2 first traffics to the cilium base before TOP domain dependent entry. Our results suggest that PC2 localisation to the cilium is necessary to prevent PKD.
Author Correction: Coherent diffractive imaging of microtubules using an X-ray laser
Authors: Brändén Gisela , Hammarin Greger , Harimoorthy Rajiv , Johansson Alexander , Arnlund David , Malmerberg Erik , Barty Anton , Tångefjord Stefan , Berntsen Peter , DePonte Daniel P. , Seuring Carolin , White Thomas A. , Stellato Francesco , Bean Richard , Beyerlein Kenneth R. , Chavas Leonard M. G. , Fleckenstein Holger , Gati Cornelius , Ghoshdastider Umesh , Gumprecht Lars , Oberthür Dominik , Popp David , Seibert Marvin , Tilp Thomas , Messerschmidt Marc , Williams Garth J. , Loh N. Duane , Chapman Henry N. , Zwart Peter , Liang Mengning , Boutet Sébastien , Robinson Robert C. , Neutze Richard
Published: September 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Ab initio investigation of the cyclodehydrogenation process for polyanthrylene transformation to graphene nanoribbons
Authors: Xiao Zhongcan , Ma Chuanxu , Lu Wenchang , Huang Jingsong , Liang Liangbo , Hong Kunlun , Li An-Ping , Sumpter Bobby G. , Bernholc Jerzy
Published: September 2019

Graphene nanoribbons (GNRs) can be synthesized from molecular precursors with atomic precision. A prominent case is the 7-atom-wide armchair GNR made from 10,10′-dibromo-9,9′-bianthryl (DBBA) precursors on metal substrates through dehalogenation/polymerization followed by cyclodehydrogenation. We investigate the key aspects of the cyclodehydrogenation process by evaluating the energy profiles of various reaction pathways using density functional theory and the nudged elastic band method. The metal substrate plays a critical catalytic role by providing stronger adsorption for products and facilitating H desorption. For polyanthrylene on an extra layer of GNR on Au, the underlying GNR insulates it from the Au substrate and increases the reaction barriers, rendering the polyanthrylene “quasi-freestanding”. However, positive charge injection can induce localized cyclodehydrogenation. We find that this is due to the stabilization of an intermediate state through an arenium ion mechanism and favorable orbital symmetries. These results provide mechanistic insight into the effects of the metal substrate and charge injection on cyclodehydrogenation during GNR synthesis and offer guidance for the design and growth of new graphitic structures.
Variational ansatz-based quantum simulation of imaginary time evolution
Authors: McArdle Sam , Jones Tyson , Endo Suguru , Li Ying , Benjamin Simon C. , Yuan Xiao
Published: September 2019

Imaginary time evolution is a powerful tool for studying quantum systems. While it is possible to simulate with a classical computer, the time and memory requirements generally scale exponentially with the system size. Conversely, quantum computers can efficiently simulate quantum systems, but not non-unitary imaginary time evolution. We propose a variational algorithm for simulating imaginary time evolution on a hybrid quantum computer. We use this algorithm to find the ground-state energy of many-particle systems; specifically molecular hydrogen and lithium hydride, finding the ground state with high probability. Our method can also be applied to general optimisation problems and quantum machine learning. As our algorithm is hybrid, suitable for error mitigation and can exploit shallow quantum circuits, it can be implemented with current quantum computers.
The chemical and attitudinal differences between commercial and artisanal products
Authors: Cirne Cecilia T. , Tunick Michael H. , Trout Rosemary E.
Published: September 2019

Here we report a study of artisanal grain, coffee, ice cream, cheese, and chocolate made in the Philadelphia and New York areas, exploring the chemistry responsible for the differences between artisanal and mass-produced food, the rationale that artisans have toward making their products, and consumer attitudes toward purchasing artisanal food. The contrasting techniques used in manufacturing these two classes of food lead to differences in composition, flavor, and texture. Dairy products made from pasture-fed cows, for instance, display more complex flavor profiles owing to the greater variety of plants the animals consume. Consumers are willing to pay more for artisanal food, feeling that it tastes better, is healthier, and helps support family-owned operations. Producers not only want to be able to control their businesses, but also wish to create better and more-authentic food in an environmentally friendly manner. The psychology surrounding artisanal food is partly based on their chemistry.
Pre-existing yellow fever immunity impairs and modulates the antibody response to tick-borne encephalitis vaccination
Authors: Bradt Victoria , Malafa Stefan , von Braun Amrei , Jarmer Johanna , Tsouchnikas Georgios , Medits Iris , Wanke Kerstin , Karrer Urs , Stiasny Karin , Heinz Franz X.
Published: September 2019

Flaviviruses have an increasing global impact as arthropod-transmitted human pathogens, exemplified by Zika, dengue, yellow fever (YF), West Nile, Japanese encephalitis, and tick-borne encephalitis (TBE) viruses. Since all flaviviruses are antigenically related, they are prone to phenomena of immunological memory (‘original antigenic sin’), which can modulate immune responses in the course of sequential infections and/or vaccinations. In our study, we analyzed the influence of pre-existing YF vaccine-derived immunity on the antibody response to TBE vaccination. By comparing samples from YF pre-vaccinated and flavivirus–naive individuals, we show that YF immunity not only caused a significant impairment of the neutralizing antibody response to TBE vaccination but also a reduction of the specific TBE virus neutralizing activities (NT/ELISA-titer ratios). Our results point to a possible negative effect of pre-existing cross-reactive immunity on the outcome of flavivirus vaccination that may also pertain to other combinations of sequential flavivirus infections and/or vaccinations.
Human hand kinematic data during feeding and cooking tasks
Authors: Roda-Sales Alba , Vergara Margarita , Sancho-Bru Joaquín L. , Gracia-Ibáñez Verónica , Jarque-Bou Néstor J.
Published: September 2019

This work presents a database of human hand kinematics containing data collected during the performance of a wide variety of activities of daily living involving feeding and cooking. The data were recorded using CyberGlove instrumented gloves on both hands measuring 18 degrees of freedom on each. A total of 20 subjects participated in each part of the experiment, and the objects and their arrangement were the same across subjects, although they performed the tasks in a natural non-directed way. This dataset contains a total of 1160 continuous calibrated recordings taken at 100 Hz during the performance of the tasks, with filtered signal. Statistical descriptive analyses from these data are presented. This database can be useful for machine learning purposes and prostheses control, as well as for the characterization of healthy human hand kinematics.
Exploring the reactivity of distinct electron transfer sites at CVD grown monolayer graphene through the selective electrodeposition of MoO2 nanowires
Authors: García-Miranda Ferrari Alejandro , Foster Christopher W. , Brownson Dale A. C. , Whitehead Kathryn A. , Banks Craig E.
Published: September 2019

The origin of electron transfer at Chemical Vapour Deposition (CVD) grown monolayer graphene using a polymer-free transfer methodology is explored through the selective electrodeposition of Molybdenum (di)oxide (MoO2). The electrochemical decoration of CVD monolayer graphene with MoO2 is shown to originate from the edge plane like- sites/defects. Edge plane decoration of MoO2 nanowires upon monolayer graphene is observed via electrochemical deposition over short time periods only (ca. −0.6 V for 1 second (vs. Ag/AgCl)). At more electrochemically negative potentials (ca. −1.0 V) or longer deposition times, a large MoO2 film is created/deposited on the graphene sheet, originating and expanding from the original nucleation points at edge plane like- sites/defects/wrinkles. Nanowire fabrication along the edge plane like- sites/defects of graphene is confirmed with Cyclic Voltammetry, Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM) and Raman Spectroscopy. Monitoring the electrochemical response towards [Ru(NH3)6]3+/2+ and comparing the heterogeneous electron transfer (HET) kinetics at CVD grown monolayer graphene prior and post nanowire fabrication reveals key understandings into the fundamental electrochemical properties of carbon materials. The HET kinetics ($${{\boldsymbol{k}}}_{{\boldsymbol{obs}}}^{{\bf{0}}}$$

k

obs

0

) at MoO2 nanowire decorated monolayer graphene sheets, when edge plane like- sites/defects have been coated/blocked with MoO2, are significantly reduced in comparison to the unmodified graphene alternative. Interestingly, MoO2 nucleation originates on the edge plane like- sites/defects of the graphene sheets, where the basal plane sites remain unaltered until the available edge plane like- sites/defects have been fully utilised; after which MoO2 deposition propagates towards and onto the basal planes, eventually covering the entire surface of the monolayer graphene surface. In such instances, there is no longer an observable electrochemical response. This work demonstrates the distinct electron transfer properties of edge and basal plane sites on CVD grown monolayer graphene, inferring favourable electrochemical reactivity at edge plane like- sites/defects and clarifying the origin of graphene electro-activity.
Modeling spatially and temporally complex range dynamics when detection is imperfect
Authors: Rushing Clark S. , Royle J. Andrew , Ziolkowski David J. , Pardieck Keith L.
Published: September 2019

Species distributions are determined by the interaction of multiple biotic and abiotic factors, which produces complex spatial and temporal patterns of occurrence. As habitats and climate change due to anthropogenic activities, there is a need to develop species distribution models that can quantify these complex range dynamics. In this paper, we develop a dynamic occupancy model that uses a spatial generalized additive model to estimate non-linear spatial variation in occupancy not accounted for by environmental covariates. The model is flexible and can accommodate data from a range of sampling designs that provide information about both occupancy and detection probability. Output from the model can be used to create distribution maps and to estimate indices of temporal range dynamics. We demonstrate the utility of this approach by modeling long-term range dynamics of 10 eastern North American birds using data from the North American Breeding Bird Survey. We anticipate this framework will be particularly useful for modeling species’ distributions over large spatial scales and for quantifying range dynamics over long temporal scales.
Computer Aided Patterning Design for Self-Assembled Microsphere Lithography (SA-MSL)
Authors: Lees Rhiannon , Cooke Michael D. , Balocco Claudio , Gallant Andrew
Published: September 2019

In this paper, we use a finite difference time domain solver to simulate the near field optical properties of self-assembled microsphere arrays when exposed to an incoherent light source. Such arrays are typically used for microsphere lithography where each sphere acts as a ball lens, focusing ultraviolet light into an underlying photoresist layer. It is well known that arrays of circular features can be patterned using this technique. However, here, our simulations show that additional nanometer scale features can be introduced to the pattern by optimising the sphere dimensions and exposure conditions. These features are shown to arise from the contact points between the microspheres which produce paths for light leakage. For hexagonally close packed arrays, the six points of contact lead to star shapes in the photoresist. These star shapes have subfeature sizes comparable to the current achievable resolution of low-cost fabrication techniques.
Extracellular vesicle-coupled miRNA profiles in follicular fluid of cows with divergent post-calving metabolic status
Authors: Hailay Tsige , Hoelker Michael , Poirier Mikhael , Gebremedhn Samuel , Rings Franca , Saeed-Zidane Mohammed , Salilew-Wondim Dessie , Dauben Christina , Tholen Ernst , Neuhoff Christiane , Schellander Karl , Tesfaye Dawit
Published: September 2019

Most high-yielding dairy cows enter a state of negative energy balance (NEB) during early lactation. This, in turn, results in changes in the level of various metabolites in the blood and follicular fluid microenvironment which contributes to disturbed fertility. Extracellular vesicles (EVs) are evolutionarily conserved communicasomes that transport cargo of miRNA, proteins and lipids. EV-coupled miRNAs have been reported in follicular fluid. However, the association between postpartum NEB and EV-coupled miRNA signatures in follicular fluid is not yet known. Energy balance analysis in lactating cows shortly after post-calving revealed that the majority of the cows exhibited transiently negative energy balance levels, whereas the remaining cows exhibited either consistently negative or consistently positive energy levels. Metabolic status was associated with EV-coupled miRNA composition in the follicular fluid. Cows experiencing NEB showed reduced expression of a large number of miRNAs while cows with positive energy balances primarily exhibited elevated expression of EV-coupled miRNAs. The miRNAs that were suppressed under NEB were found to be involved in various metabolic pathways. This is the first study to reveal the presence of an association between EV-coupled miRNA in follicular fluid and metabolic stress in dairy cows. The involvement of differentially expressed miRNAs in various pathways associated with follicular growth and oocyte maturation suggest the potential involvement of specific follicular miRNAs in oocyte developmental competence, which may partially explain reduced fertility in cows due to post-calving metabolic stress.
Homeobox code model of heterodont tooth in mammals revised
Authors: Wakamatsu Yoshio , Egawa Shiro , Terashita Yukari , Kawasaki Hiroshi , Tamura Koji , Suzuki Kunihiro
Published: September 2019

Heterodonty is one of the hallmarks of mammals. It has been suggested that, homeobox genes, differentially expressed in the ectomesenchyme of the jaw primordium along the distal-proximal axis, would determine the tooth classes (homeobox code model) based on mouse studies. Because mouse has highly specialized tooth pattern lacking canine and premolars (dental formula: 1003/1003, for upper and lower jaws, respectively), it is unclear if the suggested model could be applied for mammals with all tooth classes, including human. We thus compared the homeobox code gene expressions in various mammals, such as opossum (5134/4134), ferret (3131/3132), as well as mouse. We found that Msx1 and BarX1 expression domains in the jaw primordium of the opossum and ferret embryos show a large overlap, but such overlap is small in mouse. Detailed analyses of gene expressions and subsequent morphogenesis of tooth germ in the opossum indicated that the Msx1/BarX1 double-positive domain will correspond to the premolar region, and Alx3-negative/Msx1-positive/BarX1-negative domain will correspond to canine. This study therefore provides a significant update of the homeobox code model in the mammalian heterodonty. We also show that the modulation of FGF-mediated Msx1 activation contributes to the variation in the proximal Msx1 expression among species.
Systemic delivery and SPECT/CT in vivo imaging of 125I-labelled oncolytic adenoviral mutants in models of pancreatic cancer
Authors: Stella Man Y. K. , Foster Julie , Carapuça Elisabete , Davies James A. , Parker Alan L. , Sosabowski Jane , Halldén Gunnel
Published: September 2019

Early phase clinical trials have demonstrated good therapeutic index for oncolytic adenoviruses in patients with solid tumours when administered intratumorally, resulting in local tumour elimination. Entrapment and binding of adenovirus to erythrocytes, blood factors, and neutralising antibodies have prevented efficient systemic delivery and targeting of distant lesions in the clinic. We previously generated the novel replication-selective Ad-3∆-A20T to improve tumour targeting by increasing the viral dose at distant sites. Here, we developed a protocol to directly radiolabel the virus for rapid and sensitive detection by single-photon emitted computed tomography (SPECT/CT) providing a convenient method for determining biodistribution following intravenous administration in murine models. Longitudinal whole-body scans, demonstrated efficient viral uptake in pancreatic Suit-2 and Panc04.03 xenografts with trace amounts of 125I-Ad-3∆-A20T up to 48 h after tail vein delivery. Hepatic and splenic radioactivity decreased over time. Analysis of tissues harvested at the end of the study, confirmed potency and selectivity of mutant viruses. Ad-3∆-A20T-treated animals showed higher viral genome copy numbers and E1A gene expression in tumors than in liver and spleen compared to Ad5wt. Our direct radiolabeling approach, allows for immediate screening of novel oncolytic adenoviruses and selection of optimal viral genome alterations to generate improved mutants.
Lipocalin 2 Does Not Play A Role in Celastrol-Mediated Reduction in Food Intake and Body Weight
Authors: Feng Xudong , Guan Dongxian , Auen Thomas , Choi Jae Won , Salazar-Hernandez Mario Andres , Faruk Farhana , Copps Kyle D. , Ozcan Umut
Published: September 2019

Celastrol is a leptin-sensitizing agent with profound anti-obesity effects in diet-induced obese (DIO) mice. However, the genes and pathways that mediate celastrol-induced leptin sensitization have not been fully understood. By comparing the hypothalamic transcriptomes of celastrol and vehicle-treated DIO mice, we identified lipocalin-2 (Lcn2) as the gene most strongly upregulated by celastrol. LCN2 was previously suggested as an anorexigenic and anti-obesity agent. Celastrol increased LCN2 protein levels in hypothalamus, liver, fat, muscle, and bone marrow, as well as in the plasma. However, genetic deficiency of LCN2 altered neither the development of diet-induced obesity, nor the ability of celastrol to promote weight loss and improve obesity-associated dyshomeostasis. We conclude that LCN2 is dispensable for both high fat diet-induced obesity and its therapeutic reduction by celastrol.