bluuebunny/crossref_metadata_2025 huggingface dataset:
Decoupling gene knockout effects from gene functions by evolutionary analyses
Authors: Liu Li , Liu Mengdi , Zhang Di , Deng Shanjun , Chen Piaopiao , Yang Jing , Xie Yunhan , He Xionglei
Published: July 2019

Genic functions have long been confounded by pleiotropic mutational effects. To understand such genetic effects, we examine HAP4, a well-studied transcription factor inSaccharomyces cerevisiaethat functions by forming a tetramer with HAP2, HAP3, and HAP5. Deletion of HAP4 results in highly pleiotropic gene expression responses, some of which are clustered in related cellular processes (clustered effects) while most are distributed randomly across diverse cellular processes (distributed effects). Strikingly, the distributed effects that account for much of HAP4 pleiotropy tend to be non-heritable in a population, suggesting they have little evolutionary consequences. Indeed, these effects are poorly conserved in closely related yeasts. We further show substantial overlaps of clustered effects, but not distributed effects, among the four genes encoding the HAP2/3/4/5 tetramer. This pattern holds for other biochemically characterized yeast protein complexes or metabolic pathways. Examination of a set of cell morphological traits of the deletion lines yields consistent results. Hence, only some gene deletion effects support related biochemical understandings with the rest being pleiotropic and evolutionarily decoupled from the gene’s normal functions.
Partners in health? Investigating social genetic effects for married and cohabiting couples
Authors: Mandemakers Jornt , Otten Kasper
Published: July 2019

‘Social contagion’ research suggests that health behaviors (BMI, smoking, drinking, etc.) spread through social networks, including dyadic ties such as between married/cohabiting partners. However, separating contagion from assortative mating (‘like seeks like’) and shared environmental factors remains notoriously difficult in observational studies. It is not possible to obtain exogenous variation in long-term partnerships (‘random mating’), but genetic approaches can offer a novel way to examine partner similarity and the role of social contagion. This paper explores possible social genetic effects among partners, i.e., effects of the partner’s genes on one’s own behavior. We use the longitudinal Health and Retirement Study with data on health behavior and genomic data for both ego and his/her partner to examine social genetic effects for BMI, drinking, and smoking behavior. For each outcome, we find support for social genetic effects. Americans of European descent were more overweight if they had partners with higher polygenic scores for BMI net of their own polygenic score. Similar findings were found for the number of drinks per week and cigarettes per day. Longitudinal analyses that conditioned on past health behavior of both spouses confirmed these findings. We further explored whether susceptibility to the partner’s influence differed between men and women, but did not find consistent differences across outcomes. Findings are further discussed in the light of ramifications of social genetic effects for the social and biological sciences.
Bayesian-Maximum-Entropy reweighting of IDP ensembles based on NMR chemical shifts
Authors: Crehuet Ramon , Buigues Pedro J. , Salvatella Xavier , Lindorff-Larsen Kresten
Published: July 2019

Bayesian and Maximum Entropy approaches allow for a statistically sound and systematic fitting of experimental and computational data. Unfortunately, assessing the relative confidence in these two types of data remains difficult as several steps add unknown error. Here we propose the use of a validation-set method to determine the balance, and thus the amount of fitting. We apply the method to synthetic NMR chemical shift data of an intrinsically disordered protein. We show that the method gives consistent results even when other methods to assess the amount of fitting cannot be applied. Finally, we also describe how the errors in the chemical shift predictor can lead to an incorrect fitting and how using secondary chemical shifts could alleviate this problem.
Lake overturn as a key driver for methane oxidation
Authors: Zimmermann M. , Mayr M. J. , Bouffard D. , Eugster W. , Steinsberger T. , Wehrli B. , Brand A. , Bürgmann H.
Published: July 2019

Many seasonally stratified lakes accumulate substantial amounts of the greenhouse gas methane in the anoxic zone. Methane oxidizing bacteria in the water column act as a converter, oxidizing methane into carbon dioxide and biomass before it reaches the atmosphere. Current observations and estimates of this methane oxidation efficiency are diverging, especially for the lake overturn period. Here we combine a model of turbulent mixing, gas exchange and microbial growth with a comprehensive data set for autumn mixing to quantify the relevant physical and microbial processes. We show that the microbial methane converter is effectively transforming the increased methane flux during the overturn period. Only rare events of pronounced surface cooling in combination with persistently strong wind can trigger substantial outgassing. In the context of climate change, these results suggest that changes in the frequency of storms may be even more important for methane emissions from temperate lakes than gradual warming.
Evaluating the ecological impacts of pesticide seed treatments on arthropod communities in a grain crop rotation
Authors: Dubey Aditi , Lewis Margaret T. , Dively Galen P. , Hamby Kelly A.
Published: July 2019

While many studies have investigated non-target impacts of neonicotinoid seed treatments (NSTs), they usually take place within a single crop and focus on specific pest or beneficial arthropod taxa.

We compared the impacts of three seed treatments to an untreated control: imidacloprid + fungicide products, thiamethoxam + fungicide products, and fungicide products alone in a three-year crop rotation of full-season soybean, winter wheat, double-cropped soybean and maize. Specifically, we quantified neonicotinoid residues in the soil and in weedy winter annual flower buds and examined treatment impacts on soil and foliar arthropod communities, and on plant growth and yield.

Trace amounts of insecticide were found in winter annual flowers of one species in one site year, which did not correspond with our treatments. Although low levels of insecticide residues were present in the soil, residues were not persistent. Residues were highest in the final year of the study, suggesting some accumulation.

We observed variable impacts of NSTs on the arthropod community; principle response curve analysis, diversity and evenness values exhibited occasional community disturbances, and treatments impacted the abundance of various taxa. Overall, imidacloprid had a greater effect than thiamethoxam, with the fungicide only treatment also occasionally impacting communities and individual taxa.

Pest pressure was low throughout the study, and although pest numbers were reduced by the insecticides no corresponding increases in yield were observed. However, the fungicide products contributed to higher yields in wheat.

Synthesis and applications. Pesticide seed treatments can disturb arthropod communities, even when environmental persistence and active ingredient concentrations are low. The foliar community in wheat and maize exhibited a trend of increasing disturbance throughout the sampling period, suggesting that recovery from the impacts of NSTs is not always rapid. Our study is among the first to demonstrate that seed applied fungicides alone can disrupt arthropod communities in agroecosystems and highlights the need for further investigation into the impacts of seed applied fungicides.
Effects of nicotine on the thermodynamics of the DPPC phase coexistence region
Authors: Vieira Ernanni D. , Costa-Filho A. J. , Basso Luis. G. M.
Published: July 2019

Phase separation plays critical roles in several membrane functions, and reduction or disappearance of phase coexistence by action of membrane-interacting molecules have been implicated in membrane function impairment. Here, we applied differential scanning calorimetry, electron paramagnetic resonance (EPR), and non-linear least-squares (NLLS) spectral simulations to study the effects of nicotine, a parasympathomimetic drug, on the two-phase coexistence of dipalmitoyl phosphatidylcholine (DPPC) lipid membrane. The thermodynamic quantities describing the DPPC phase coexistence are temperature dependent, giving rise to non-linear van’t Hoff behavior. Our results showed that nicotine preferentially binds to the fluid phase and modifies the enthalpy and entropy changes of the DPPC heat capacity profile, while marginally perturbing the homogeneous gel and fluid phases. An EPR/NLLS/van’t Hoff analysis of the DPPC phase coexistence revealed that nicotine significantly modified the temperature dependence of the free energy change of the two-phase equilibrium from a cubic to a parabolic behavior, resulting in an alteration of the thermodynamical driving force and the balance of the non-covalent interactions of the lipids in equilibrium. The thermotropic behavior of the enthalpy, entropy, and heat capacity changes, as determined by EPR, indicated that nicotine modified the relative contributions of hydrogen-bonding, electrostatic interactions, and conformational entropy of the lipids to the thermodynamics of the phase coexistence. The predominantly entropically-driven gel-fluid transition in nicotine-free DPPC changes to a temperature-triggered entropically-driven or enthalpically-driven process in nicotine-bound DPPC. Further applications of this thermodynamic EPR/NLLS/van’t Hoff analysis are discussed.
Delineating the site of interaction on the intracellular domain of 5-HT3A receptors with the chaperone protein RIC-3
Authors: Pirayesh Elham , Stuebler Antonia G. , Pandhare Akash , Jansen Michaela
Published: July 2019

The serotonin type 3A (5-HT3A) receptor is a homopentameric cation-selective member of the pentameric ligand-gated ion channel (pLGIC) superfamily. Members of this superfamily assemble from five subunits, each of which consists of three domains, extracellular (ECD), transmembrane (TMD), and intracellular domain (ICD). Previously, we have also demonstrated that 5-HT3A-ICD is required and sufficient for the interaction between 5-HT3A and RIC-3. Additionally, we have shown that 5-HT3A-ICD fused to maltose binding protein (MBP) directly interacts with the chaperone protein resistance to inhibitors of choline esterase (RIC-3), without the involvement of other protein(s). To elucidate the molecular determinants of this interaction we developed different MBP-fused 5-HT3A-ICD constructs by deletion of large portions of its amino acid sequence. We have expressed seven mutants in Escherichia coli and purified them to homogeneity. Using a RIC-3 affinity pull-down assay, the interaction of MBP-5HT3A-ICD constructs and RIC-3 is investigated. Furthermore, we co-expressed 5-HT3A and 5-HT3AB, a heteromeric form of 5-HT3Rs, with RIC-3 in Xenopus oocytes to compare their interaction with RIC-3 in-vivo by two electrode voltage clamp (TEVC) recordings. Full-length 5-HT3A-and 5-HT3AB mediated currents are significantly reduced when RIC-3 is co-expressed in either condition. In summary, we identify a 24-amino acid long segment of the 5-HT3A-ICD as a molecular determinant for the interaction between the 5-HT3A-ICD and RIC-3.

Statement of Significance

The chaperone protein RIC-3 is known to modulate the functional surface expression of cation-conducting pentameric ligand-gated ion channels. Previously we have demonstrated that the intracellular domain of serotonin channels mediates this effect. Here we provide experimental evidence for a 24-amino acid long segment within the 115-amino acid long intracellular domain as a determinant for RIC-3 interaction. Recently it was found experimentally that the identified segment contains an alpha helix that has been observed or predicted to be present in other cation-conducting channels. The present work provides novel insights into protein-protein interactions that are likely also relevant for other cation-conducting members of this large ion channel family that includes nACh and 5-HT3 receptors.
Metal bridge in S4 segment supports helix transition inShakerchannel
Authors: Bassetto Carlos A Z , Carvalho-de-Souza João Luis , Bezanilla Francisco
Published: July 2019

Voltage-gated ion channels play important roles in physiological processes, especially in excitable cells, where they shape the action potential. In S4-based voltage sensors voltage-gated channels, a common feature is shared: the transmembrane segment 4 (S4) contains positively charged residues intercalated by hydrophobic residues. Although several advances have been made in understating how S4 moves through a hydrophobic plug upon voltage changes, possible helix transition from α-to 310-helix in S4 during activation process is still unresolved. Here, we have mutated several hydrophobic residues from I360 to F370 in the S4 segment into histidine, ini, i+3andi, i+6ori, i+4andi, i+7pairs, to favor 310- or α-helical conformations, respectively. We have taken advantage that His can be coordinated by Zn+2to promote metal ion bridges and we have found that the histidine introduced at position 366 (L366H) can interact with the introduced histidine at position 370 (stabilizing that portion of the S4 segment in α-helical conformation). In presence of 20 μM of Zn+2, the activation currents of L366H:F370H channels were slowed down by a factor of 3.5, the voltage-dependence is shifted by 10 mV towards depolarized potentials with no change on the deactivation time constant. Our data supports that by stabilizing a region of the S4 segment in α-helical conformation a closed(resting or intermediate)state is stabilized rather than destabilizing the open (active)state. Taken together, our data indicates that the S4 undergoes α-helical conformation to a short-lived different secondary structure transiently before reaching theactivestate in the activation process.

STATEMENT OF SIGNIFICANCE

Conformational transitions between α-helix and 310-helix in the S4 segment ofShakerpotassium channel during gating has been under debate. The present study shows the coordination by Zn2+of a pair of engineered histidine residues (L366H:F370H) in the intermediate region of S4 in Shaker, favoring α-helical conformation. In presence of 20μM of Zn+2the activation currents of L366H:F370H channels become slower, with 10 mV positive shift in the voltage-dependence and no effects on deactivation time constants suggesting a stabilization of a closed state rather than destabilization the open(active)state. Collectively, our data indicate that S4 undergoes secondary structure changes, including a short-lived secondary structure transition, when S4 moves from therestingto theactivestate during activation.
Testis single-cell RNA-seq reveals the dynamics ofde novogene transcription and germline mutational bias inDrosophila
Authors: Witt Evan , Benjamin Sigi , Svetec Nicolas , Zhao Li
Published: July 2019

The testis is a peculiar tissue in many respects. It shows patterns of rapid gene evolution and provides a hotspot for the origination of genetic novelties such asde novogenes, duplications and mutations. To investigate the expression patterns of genetic novelties across cell types, we performed single-cell RNA-sequencing of adultDrosophilatestis. We found that new genes were expressed in various cell types, the patterns of which may be influenced by their mode of origination. In particular, lineage-specificde novogenes are commonly expressed in early spermatocytes, while young duplicated genes are often bimodally expressed. Analysis of germline substitutions suggests that spermatogenesis is a highly reparative process, with the mutational load of germ cells decreasing as spermatogenesis progresses. By elucidating the distribution of genetic novelties across spermatogenesis, this study provides a deeper understanding of how the testis maintains its core reproductive function while being a hotbed of evolutionary innovation.
A popular Indian clove-based mosquito repellent is a false economy
Authors: Tan Kaiming , Faierstein Gabriel B. , Xu Pingxi , Barbosa Rosângela M.R. , Buss Garrison K. , Leal Walter S.
Published: July 2019

Insect repellents are important prophylactic tools for travelers to and populations living in endemic areas of malaria, dengue, encephalitis, and other vector-borne diseases, and the first line of defense against emerging arboviruses. However, the cost of daily applications of even the most affordable and the gold standard of insect repellents, DEET, is still high for low-income populations where repellents are needed the most. An Indian clove-based homemade recipe has been presented as a panacea. We analyzed this homemade repellent and confirmed by behavioral measurements and odorant receptor responses that eugenol is the active ingredient in this formulation. Prepared as advertised, this homemade repellent is ineffective, whereas 5X more concentrated extracts from the brand most enriched in eugenol showed moderate repellency activity against Culex quinquefasciatus and Aedes aegypti. DEET showed higher performance when compared to the 5X concentrated formulation and is available in the same market at a lower price than the cost of the ingredients to prepare the homemade formulation.
A novel metric reveals previously unrecognized distortion in dimensionality reduction of scRNA-seq data
Authors: Cooley Shamus M. , Hamilton Timothy , Aragones Samuel D. , Ray J. Christian J. , Deeds Eric J.
Published: July 2019

High-dimensional data are becoming increasingly common in nearly all areas of science. Developing approaches to analyze these data and understand their meaning is a pressing issue. This is particularly true for single-cell RNA-seq (scRNA-seq), a technique that simultaneously measures the expression of tens of thousands of genes in thousands to millions of single cells. The emerging consensus for analysis workflows significantly reduces the dimensionality of the dataset before performing downstream analysis, such as assignment of cell types. One problem with this approach is that dimensionality reduction can introduce substantial distortion into the data; consider the familiar example of trying to represent the three-dimensional earth as a two-dimensional map. It is currently unclear if such distortion affects analysis of scRNA-seq data. Here, we introduce a straightforward approach to quantifying this distortion by comparing the local neighborhoods of points before and after dimensionality reduction. We found that popular techniques like t-SNE and UMAP introduce substantial distortion even for relatively simple simulated data sets. For scRNA-seq data, we found the distortion in local neighborhoods was often greater than 95% in the representations typically used for downstream analyses. This level of distortion can introduce errors into cell type identification, pseudotime ordering, and other analyses. We found that principal component analysis can generate accurate embeddings, but only when using dimensionalities that are much higher than typically used in scRNA-seq analysis. Our work suggests the need for a new generation of dimensional reduction algorithms that can accurately embed high dimensional data in its true latent dimension.
Alcohol preferring P rats exhibit aversion resistant drinking of alcohol adulterated with quinine
Authors: Timme Nicholas M. , Linsenbardt David , Timm Maureen , Galbari Taylor , Cornwell Ethan , Lapish Christopher
Published: July 2019

Understanding why some people continue to drink alcohol despite negative consequences and others do not is a central problem in the study of alcohol use disorder (AUD). In this study, we used alcohol preferring P rats (a strain bred to prefer to drink alcohol, a model for genetic risk for AUD) and Wistars (control) to examine drinking despite negative consequences in the form of an aversive bitter taste stimuli produced by quinine. Animals were trained to consume 10% ethanol in a simple Pavlovian conditioning task that paired alcohol access with an auditory stimulus. When the alcohol was adulterated with quinine (0.1 g/L), P rats continued to consume alcohol+quinine at the same rate as unadulterated alcohol, despite a demonstrated aversion to quinine adulterated alcohol when given a choice between adulterated and unadulterated alcohol in the home cage. Conversely, Wistars decreased consumption of quinine adulterated alcohol in the task, but continued to try the alcohol+quinine solution at similar rates to unadulterated alcohol. These results indicate that following about 8 weeks of alcohol consumption P rats exhibit aversion resistant drinking. This model could be used in future work to explore how biological basis of alcohol consumption and genetic risk for excessive drinking lead to drinking that is resistant to devaluation.
Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke
Authors: Abraham Gad , Malik Rainer , Yonova-Doing Ekaterina , Salim Agus , Wang Tingting , Danesh John , Butterworth Adam , Howson Joanna , Inouye Michael , Dichgans Martin
Published: July 2019

Recent genome-wide association studies in stroke have enabled the generation of genomic risk scores (GRS) but the predictive power of these GRS has been modest in comparison to established stroke risk factors. Here, using a meta-scoring approach, we developed a metaGRS for ischaemic stroke (IS) and analysed this score in the UK Biobank (n=395,393; 3075 IS events by age 75). The metaGRS hazard ratio for IS (1.26, 95% CI 1.22-1.31 per standard deviation increase of the score) doubled that of previous GRS, enabling the identification of a subset of individuals at monogenic levels of risk: individuals in the top 0.25% of metaGRS had a three-fold increased risk of IS. The metaGRS was similarly or more predictive when compared to established risk factors, such as family history, blood pressure, body mass index and smoking status. For participants within accepted guideline levels for established stroke risk factors, we found substantial variation in incident stroke rates across genomic risk backgrounds. We further estimated combinations of reductions needed in modifiable risk factors for individuals with different levels of genomic risk and suggest that, for individuals with high metaGRS, achieving currently recommended risk factor levels may be insufficient to mitigate risk.
Cannabidiol attenuates seizures and EEG abnormalities in Angelman syndrome model mice
Authors: Gu Bin , Zhu Manhua , Glass Madison R. , Rougié Marie , Nikolova Viktoriya D. , Moy Sheryl S. , Carney Paul R. , Philpot Benjamin D.
Published: July 2019

Angelman syndrome (AS) is a neurodevelopmental disorder characterized by intellectual disability, lack of speech, ataxia, EEG abnormalities, and epilepsy. Seizures in AS individuals are often refractory to existing antiepileptic medications. Therefore, there is an unmet need for better seizure control, which could potentially improve other symptomatic domains such as cognitive function. Cannabidiol (CBD), a major phytocannabinoid constituent of cannabis, has anti-seizure activity and behavioral benefits in preclinical and clinical studies for some disorders associated with epilepsy, suggesting that the same could be true for AS. Here we show that acute CBD (100 mg/kg) attenuated hyperthermia- and acoustically-induced seizures in a mouse model of AS. However, neither acute CBD nor a two-weeklong course of CBD administered immediately after a kindling protocol could halt the pro-epileptogenic plasticity observed in AS model mice. CBD had a mild sedative effect, but did not have a major impact on motor performance. CBD abrogated the enhanced delta rhythms observed in AS model mice, indicating that CBD administration could also help normalize the EEG deficits observed in individuals with AS. Our results provide critical preclinical evidence supporting CBD treatment of seizures and alleviation of EEG abnormalities in AS, and will thus help guide the rational development of CBD as an AS adjunctive treatment.
Tumor cell phenotype and heterogeneity differences in IDH1 mutant vs wild-type gliomas
Authors: Berens Michael E. , Sood Anup , Barnholtz-Sloan Jill S. , Graf John F. , Cho Sanghee , Kim Seungchan , Kiefer Jeffrey , Byron Sara A. , Halperin Rebecca F. , Nasser Sara , Adkins Jonathan , Cuyugan Lori , Devine Karen , Ostrom Quinn , Couce Marta , Wolansky Leo , McDonough Elizabeth , Schyberg Shannon , Dinn Sean , Sloan Andrew E. , Prados Michael , Phillips Joanna J. , Nelson Sarah J. , Liang Winnie S. , Rusu Mirabela , Zavodszky Maria I. , Ginty Fiona
Published: July 2019

Glioma is recognized to be a highly heterogeneous CNS malignancy, whose diverse cellular composition and cellular interactions have not been well characterized. To gain new clinical- and biological-insights into the genetically-bifurcated IDH1 mutant (mt) vs wildtype (wt) forms of glioma, we integrated multiplexed immunofluorescence single cell data for 43 protein markers across cancer hallmarks, in addition to cell spatial metrics, genomic sequencing and magnetic resonance imaging (MRI) quantitative features. Molecular and spatial heterogeneity scores for angiogenesis and cell invasion differ between IDHmt and wt gliomas irrespective of prior treatment and tumor grade; these differences also persisted in the MR imaging features of peritumoral edema and contrast enhancement volumes. Longer overall survival for IDH1mt glioma patients may reflect generalized altered cellular, molecular, spatial heterogeneity which manifest in discernable radiological manifestations.
Foveal feedback supports peripheral perception of both object color and form
Authors: Weldon Kimberly B. , Woolgar Alexandra , Rich Anina N. , Williams Mark A.
Published: July 2019

Evidence from neuroimaging and brain stimulation studies suggest that visual information about objects in the periphery is fed back to foveal retinotopic cortex in a separate representation that is essential for peripheral perception. The characteristics of this phenomenon has important theoretical implications for the role fovea-specific feedback might play in perception. In this work, we employed a recently developed behavioral paradigm to explore whether late disruption to central visual space impaired perception of color. First, participants performed a shape discrimination task on colored novel objects in the periphery while fixating centrally. Consistent with the results from previous work, a visual distractor presented at fixation ~100ms after presentation of the peripheral stimuli impaired sensitivity to differences in peripheral shapes more than a visual distractor presented at other stimulus onset asynchronies. In a second experiment, participants performed a color discrimination task on the same colored objects. In a third experiment, we further tested for the foveal distractor effect with stimuli restricted to a low-level feature by using homogenous color patches. These two latter experiments resulted in a similar pattern of behavior: a central distractor presented at the critical stimulus onset asynchrony impaired sensitivity to peripheral color differences, but, importantly, the magnitude of the effect depended on whether peripheral objects contained complex shape information. These results taken together suggest that feedback to the foveal confluence is a component of visual processing supporting perception of both object form and color.
Structural comparison of p-hydroxybenzoate hydroxylase (PobA) from Pseudomonas putida with PobA from other Pseudomonas spp. and other monooxygenases
Authors: Lazar John T. , Shuvalova Ludmilla , Rosas-Lemus Monica , Kiryukhina Olga , Satchell Karla J. F. , Minasov George
Published: July 2019

The crystal structure is reported of p-hydroxybenzoate hydroxylase (PobA) from Pseudomonas putida, a possible drug target to combat tetracycline resistance, in complex with flavin adenine dinucleotide (FAD). The structure was refined at 2.2 Å resolution with four polypeptide chains in the asymmetric unit. Based on the results of pairwise structure alignments, PobA from P. putida is structurally very similar to PobA from P. fluorescens and from P. aeruginosa. Key residues in the FAD-binding and substrate-binding sites of PobA are highly conserved spatially across the proteins from all three species. Additionally, the structure was compared with two enzymes from the broader class of oxygenases: 2-hydroxybiphenyl 3-monooxygenase (HbpA) from P. nitroreducens and 2-methyl-3-hydroxypyridine-5-carboxylic acid oxygenase (MHPCO) from Mesorhizobium japonicum. Despite having only 14% similarity in their primary sequences, pairwise structure alignments of PobA from P. putida with HbpA from P. nitroreducens and MHPCO from M. japonicum revealed local similarities between these structures. Key secondary-structure elements important for catalysis, such as the βαβ fold, β-sheet wall and α12 helix, are conserved across this expanded class of oxygenases.
Multicentered hydrogen bonding in 1-[(1-deoxy-β-D-fructopyranos-1-yl)azaniumyl]cyclopentanecarboxylate (`D-fructose-cycloleucine')
Authors: Mossine Valeri V. , Barnes Charles L. , Mawhinney Thomas P.
Published: July 2019

The title compound, C12H21NO7, (I), is conformationally unstable; the predominant form present in its solution is the β-pyranose form (74.3%), followed by the β- and α-furanoses (12.1 and 10.2%, respectively), α-pyranose (3.4%), and traces of the acyclic carbohydrate tautomer. In the crystalline state, the carbohydrate part of (I) adopts the2C5β-pyranose conformation, and the amino acid portion exists as a zwitterion, with the side chain cyclopentane ring assuming theE9envelope conformation. All heteroatoms are involved in hydrogen bonding that forms a system of antiparallel infinite chains of fusedR33(6) andR33(8) rings. The molecule features extensive intramolecular hydrogen bonding, which is uniquely multicentered and involves the carboxylate, ammonium and carbohydrate hydroxy groups. In contrast, the contribution of intermolecular O...H/H...O contacts to the Hirshfeld surface is relatively low (38.4%), as compared to structures of other D-fructose-amino acids. The1H NMR data suggest a slow rotation around the C1—C2 bond in (I), indicating that the intramolecular heteroatom contacts survive in aqueous solution of the molecule as well.
Small herbivores slow down species loss up to 22 years but only at early successional stage
Authors: Chen Qingqing , Howison Ruth A. , Bakker Jan P. , Alberti Juan , Kuijper Dries P. J. , Olff Han , Smit Christian
Published: July 2019

The long‐term influence of persistent small herbivores on successional plant community configuration is rarely studied. We used a herbivore exclusion experiment along the successional gradient in a salt‐marsh system, to investigate the effects of hares and geese, and hares alone, on plant diversity at five successional stages (the earliest, two early, the intermediate and the late successional stages) in the short and long term, i.e. 7 and 22 years, respectively.

Plant diversity declined over time at all successional stages except for the earliest one. Small herbivores slowed down species decline, but only at one early successional stage.

Small herbivores slowed down species decline via decreasing dominance of preferred grass Festuca rubra in the short term, and less preferred Elytrigia atherica in the long term. The effects of hares and geese were more pronounced than hares alone, indicating an important additive role of geese, especially in the long term.

Synthesis. Small herbivores can have a strong and long‐lasting impact on plant diversity, but it highly depends on the abundance of small herbivores, which in turn depends on the quality and abundance of forage plants. A diverse herbivore community may have more positive effects on regulating plant communities.
Tree survival and growth responses in the aftermath of a strong earthquake
Authors: Allen Robert B. , MacKenzie Darryl I. , Bellingham Peter J. , Wiser Susan K. , Arnst Elise A. , Coomes David A. , Hurst Jennifer M.
Published: July 2019

The infrequent and unpredictable nature of earthquakes means that their landslide‐generated impacts on forests are rarely investigated. In montane forests, landslides are the main cause of tree death and injury during earthquakes. Landslides range from soil movements that uproot and bury trees over extensive areas to rock falls that strike individual trees. We examined unexplored relationships between tree survival and distance from an epicentre, soil‐available phosphorus (P) as an indicator of soil development and tree diameter. We expected decreased tree growth in damaged forests because of tree injury.

We used a plot network, established in 1974 and resurveyed regularly ever since, to quantify survival and growth responses 6–30 km from the epicentre of a 1994 earthquake in New Zealand's Southern Alps. Our Bayesian analysis used 8,518 trees from 250 plots that representatively sampled a naturally monospecific Nothofagus forest. As the time‐scales over which responses could emerge were unknown, we compared relationships for a pre‐earthquake period with 0–5 years post‐earthquake, and with 5+ years post‐earthquake.

Not all plots were affected by the earthquake. We found that 0–5 years post‐earthquake survival increased logarithmically with distance from the epicentre with lowered survival up to 20 km from the epicentre. Survival was low on plots with high soil‐available P. An inverted U‐shaped relationship between survival and diameter pre‐earthquake was not found 0–5 years post‐earthquake. This was because of surprisingly high survival by large trees. The earthquake most often suppressed 0–5 years post‐earthquake growth up to 15 km from the epicentre, but this was only apparent after accounting for more general growth differences among periods. The positive relationship between growth and soil‐available P pre‐earthquake and 5+ years post‐earthquake reflected enhanced growth on young soils. This contrasted with a negative effect of soil‐available P on growth 0–5 years post‐earthquake.

Synthesis. Soil‐available P, tree diameter and distance from the epicentre independently determined how tree survival and growth responded to an earthquake. The impacts on survival and growth largely occurred 0–5 years post‐earthquake and suggests a level of resilience in mountain beech forests.
Developing an Open Dialogue inspired model of systemic social work assessment in a local authority children's social care department
Authors: Clement Martin , Mc Kenny Richard
Published: July 2019

We outline a new approach to initial social work child and family assessment, focused on listening practices. The wider social context of contemporary children's services and, in particular, public concern about child death inquiries and the impacts of government's austerity policies create significant challenges for the development of listening practices. Our model seeks to develop listening practices which attend to these challenges, while retaining a focus on safe and effective social work practice. Our model develops principles of dialogicity and Open Dialogue, with systemic and narrative practices developed by Fredman and Jenkins. In crisis situations care must be taken to develop contexts for listening, where families and professionals are given opportunities to listen well to each other.

Practitioner points

Dialogicity principles and Open Dialogue practices can be applied in children's social care assessment contexts

Listening is under‐theorised in children's social care contexts; listening theory can be applied in systemic social work assessment meetings

Systemic practices can make valuable contributions to effective child and family social work

Open Dialogue practices contribute to the development of communities of practice, and can be supported through manualisation
Undermining, defusing or defending European integration? Assessing public communication of European executives in times of EU politicisation
Authors: RAUH CHRISTIAN , BES BART JOACHIM , SCHOONVELDE MARTIJN
Published: July 2019

How do mainstream political executives cue their politicised constituencies on European integration? Moving beyond static expectations that EU politicisation induces executives to either undermine, defuse or defend integration, this article theorises executives’ incentives under different configurations of public and partisan Euroscepticism in their home countries. Expectations are tested on the sentiment and complexity that executives attach to European integration in almost 9,000 public speeches delivered throughout the Euro Crisis. It is found that national leaders faced with sceptical public opinion and low levels of partisan Euroscepticism rhetorically undermine integration, whereas European Commissioners faced with similar conditions are prone to defend it. These responses intensify disproportionally with growing public Euroscepticism, but are moderated by Eurosceptic party strength in surprising ways. When such challenger parties come closer to absorbing the Eurosceptic potential in public opinion, executive communication turns more positive again but also involves less clear rhetorical signals. These findings move beyond existing uniform expectations on mainstream responses to Eurosceptic challenges and highlight the relevance of different domestic configurations of EU politicisation.
Prehospital extracorporeal cardiopulmonary resuscitation for out‐of‐hospital cardiac arrest: A retrospective eligibility study
Authors: Kilner Thomas , Stanton Benjamin L , Mazur Stefan M
Published: July 2019

Objective

We sought to identify out‐of‐hospital cardiac arrest (OOHCA) patients who might benefit from a future prehospital extracorporeal cardiopulmonary resuscitation (ECPR) programme in a moderately sized city. We described the 2014 OOHCA data and identified those who fulfilled hypothetical prehospital ECPR eligibility criteria.

Methods

We identified patients aged 18–65 years in cardiac arrest, where CPR was commenced by paramedics on arrival. Traumatic cardiac arrest and end‐of‐life needs were patient exclusions. Patients were then included in one of three hypothetical ‘ECPR eligible’ groups. Patients were included in an ‘ECPR eligible’ group if they met author agreed criteria. Select patients in refractory VT/VF; pulseless electrical activity (PEA); and non‐refractory VT/VF, or asystole with subsequent VT/VF or transient return of spontaneous circulation (ROSC), were assigned to three separate groups. Descriptive statistics were applied to each group. Outcomes of ECPR eligible patients who developed sustained ROSC after 20 min of conventional CPR were characterised.

Results

A total of 206 patients were included. A significant positive association between initial shockable rhythm (odds ratio [OR] 15.32, confidence interval [CI] 5.4–43.2) and sustained ROSC, and PEA (OR 6.93, CI 2.4–19.8) and sustained ROSC, versus asystole was identified (P < 0.001). Sixty‐eight (33%) patients were eligible for one of the hypothetical ECPR groups. Twelve (17.6%) of the 68 ECPR eligible patients developed sustained ROSC after 20 min of conventional CPR, with only two surviving neurologically intact to hospital discharge.

Conclusion

Sixty‐three (30.6%) patients could have derived benefit from a prehospital ECPR programme. Further analyses of prehospital ECPR logistics and economics are necessary to ensure that any future prehospital ECPR programme is effective and efficient.
Does ambulatory and fast track allocation reduce immersion in acute and resuscitation training, and impair career satisfaction and job longevity for emergency medicine registrars?
Authors: Ting Joseph
Published: July 2019

Although dedicated sections for non‐acute care in the ED is recognised to improve patient flow and reduce ED congestion, there is anecdotal feedback that it detracts from work satisfaction and potentially career longevity and sustainability. Although allocation to fast track shifts reflects contemporary emergency medicine as practiced in Australasia, it may reduce registrar immersion on acute and resuscitation training.
Anxiety and alcohol in the working‐age population are driving a rise in mental health‐related emergency department presentations: 15 year trends in emergency department presentations in Western Australia
Authors: Yap Matthew , Tuson Matthew , Whyatt David , Vickery Alistair
Published: July 2019

Objective

To evaluate age, gender and disease‐specific trends in ED for mental health presentations over 15 years.

Methods

The study population consisted of residents of metropolitan Perth, Western Australia, presenting to Perth ED between 1 July 2002 and 30 June 2017. Population rates of mental health‐related ED presentations per year were calculated.

Results

Rates of mental health ED presentations are significantly increasing in the working‐age population for those with stress and anxiety‐related diagnoses, particularly in younger females, and also for alcohol‐related presentations for those aged 10–49 years, particularly in males.

Conclusion

The present study demonstrates that increased rates of mental health‐related ED presentations are driven by increased rates of presentation for stress and anxiety‐related and alcohol‐related presentations in both genders across the working‐age population.
Genome‐wide characterization and developmental expression profiling of long non‐coding RNAs in Sogatella furcifera
Authors: Chang Zhao‐Xia , Ajayi Olugbenga Emmanuel , Guo Dong‐Yang , Wu Qing‐Fa
Published: July 2019

The genome‐wide characterization of long non‐coding RNA (lncRNA) in insects demonstrates their importance in fundamental biological processes. Essentially, an in‐depth understanding of the functional repertoire of lncRNA in insects is pivotal to insect resources utilization and sustainable pest control. Using a custom bioinformatics pipeline, we identified 1861 lncRNAs encoded by 1852 loci in the Sogatella furcifera genome. We profiled lncRNA expression in different developmental stages and observed that the expression of lncRNAs is more highly temporally restricted compared to protein‐coding genes. More up‐regulated Sogatella furcifera lncRNA expressed in the embryo, 4th and 5th instars, suggesting that increased lncRNA levels may play a role in these developmental stages. We compared the relationship between the expression of Sogatella furcifera lncRNA and its nearest protein gene and found that lncRNAs were more correlated to their downstream coding neighbors on the opposite strand. Our genome‐wide profiling of lncRNAs in Sogatella furcifera identifies exciting candidates for characterization of lncRNAs, and also provides information on lncRNA regulation during insect development.
Determination of Heterocyclic Amines in Meat Matrices Using Enhanced Matrix Removal‐Lipid Extraction and Liquid Chromatography–Tandem Mass Spectrometry
Authors: Linghu Ziyi , Karim Faris , Taghvaei Mostafa , Smith J. Scott
Published: July 2019

A simple, fast, and efficient method, “enhanced matrix removal of lipids” (EMR‐lipid), was proposed, optimized, and validated for identifying five polar heterocyclic amines (HCAs) in meat samples that ranged from high‐protein (beef and chicken) to high‐fat (pork bacon) matrices. The protocol involves an initial solid–liquid phase extraction followed by a rapid dispersive solid‐phase extraction using EMR‐lipid sorbents and salting‐out partitioning. Acetonitrile containing formic acid at two levels (1% and 2%) efficiently extracted HCAs from different meat matrices. Liquid chromatography–tandem mass spectrometry (MS/MS) with selective reaction monitoring mode was developed for qualitative and quantitative analysis. The highest MS/MS responses and better peak separation of analytes were achieved by adjusting mobile phases to pH 3.0 with instrumental detection limits between 0.01 and 0.05 ng/mL. Good linearity of standard curves was obtained in both pure solvents and postspiked meat extracts between 0.5 and 50.0 ng/mL. The validation results showed good precision, accuracy, and sensitivity for detecting HCAs in spiked meat samples. Satisfactory recoveries of four HCAs were achieved: 65% to 111% in beef, 71% to 106% in bacon, and 42% to 77% in chicken. Matrix effects were also assessed and showed less than –20% of ion suppression in bacon extract, while a medium to high signal suppression was observed in beef (–37% to –55%) and chicken (–28% to –52%). This optimized EMR‐lipid method provides acceptable results and advantages for determining trace level HCAs in complex meat matrices.
Fluorescence‐based analysis of the intracytoplasmic membranes of type I methanotrophs
Authors: Whiddon Kyle T. , Gudneppanavar Ravindra , Hammer Theodore J. , West Destiny A. , Konopka Michael C.
Published: July 2019

Most methanotrophic bacteria maintain intracytoplasmic membranes which house the methane‐oxidizing enzyme, particulate methane monooxygenase. Previous studies have primarily used transmission electron microscopy or cryo‐electron microscopy to look at the structure of these membranes or lipid extraction methods to determine the per cent of cell dry weight composed of lipids. We show an alternative approach using lipophilic membrane probes and other fluorescent dyes to assess the extent of intracytoplasmic membrane formation in living cells. This fluorescence method is sensitive enough to show not only the characteristic shift in intracytoplasmic membrane formation that is present when methanotrophs are grown with or without copper, but also differences in intracytoplasmic membrane levels at intermediate copper concentrations. This technique can also be employed to monitor dynamic intracytoplasmic membrane changes in the same cell in real time under changing growth conditions. We anticipate that this approach will be of use to researchers wishing to visualize intracytoplasmic membranes who may not have access to electron microscopes. It will also have the capability to relate membrane changes in individual living cells to other measurements by fluorescence labelling or other single‐cell analysis methods.
Antimicrobial effects of microwave‐induced plasma torch (MiniMIP) treatment on Candida albicans biofilms
Authors: Handorf Oliver , Schnabel Uta , Bösel André , Weihe Thomas , Bekeschus Sander , Graf Alexander Christian , Riedel Katharina , Ehlbeck Jörg
Published: July 2019

The susceptibility of Candida albicans biofilms to a non‐thermal plasma treatment has been investigated in terms of growth, survival and cell viability by a series of in vitro experiments. For different time periods, the C. albicans strain SC5314 was treated with a microwave‐induced plasma torch (MiniMIP). The MiniMIP treatment had a strong effect (reduction factor (RF) = 2.97 after 50 s treatment) at a distance of 3 cm between the nozzle and the superior regions of the biofilms. In addition, a viability reduction of 77% after a 20 s plasma treatment and a metabolism reduction of 90% after a 40 s plasma treatment time were observed for C. albicans. After such a treatment, the biofilms revealed an altered morphology of their cells by atomic force microscopy (AFM). Additionally, fluorescence microscopy and confocal laser scanning microscopy (CLSM) analyses of plasma‐treated biofilms showed that an inactivation of cells mainly appeared on the bottom side of the biofilms. Thus, the plasma inactivation of the overgrown surface reveals a new possibility to combat biofilms.