bluuebunny/crossref_metadata_2025 huggingface dataset:
Druggable genome screen identifies new regulators of the abundance and toxicity of ATXN3, the Spinocerebellar Ataxia Type 3 disease protein
Authors: Ashraf Naila S. , Sutton Joanna R. , Yang Yemen , Ranxhi Bedri , Libohova Kozeta , Shaw Emily D. , Barget Anna J. , Todi Sokol V. , Paulson Henry L. , Costa Maria do Carmo
Published: July 2019

Background

Spinocerebellar Ataxia type 3 (SCA3, also known as Machado-Joseph disease) is a neurodegenerative disorder caused by a CAG repeat expansion encoding an abnormally long polyglutamine (polyQ) tract in the disease protein, ataxin-3 (ATXN3). No preventive treatment is yet available for SCA3. Because SCA3 is likely caused by a toxic gain of ATXN3 function, a rational therapeutic strategy is to reduce mutant ATXN3 levels by targeting pathways that control its production or stability. Here, we sought to identify genes that modulate ATXN3 levels as potential therapeutic targets in this fatal disorder.

Methods

We screened a collection of siRNAs targeting 2742 druggable human genes using a cell-based assay based on luminescence readout of polyQ-expanded ATXN3. From 317 candidate genes identified in the primary screen, 100 genes were selected for validation. Among the 33 genes confirmed in secondary assays, 15 were validated in an independent cell model as modulators of pathogenic ATXN3 protein levels. Ten of these genes were then assessed in aDrosophilamodel of SCA3, and one was confirmed as a key modulator of physiological ATXN3 abundance in SCA3 neuronal progenitor cells.

Results

Among the 15 genes shown to modulate ATXN3 in mammalian cells, orthologs ofCHD4,FBXL3,HRandMC3Rregulate mutant ATXN3-mediated toxicity in fly eyes. Further mechanistic studies of one of these genes,FBXL3, encoding a F-box protein that is a component of the SKP1-Cullin-F-box (SCF) ubiquitin ligase complex, showed that it reduces levels of normal and pathogenic ATXN3 in SCA3 neuronal progenitor cells, primarily via a SCF complex-dependent manner. Bioinformatic analysis of the 15 genes revealed a potential molecular network with connections to tumor necrosis factor-α/nuclear factor-kappa B (TNF/NF-kB) and extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathways.

Conclusions

We identified 15 druggable genes with diverse functions to be suppressors or enhancers of pathogenic ATXN3 abundance. Among identified pathways highlighted by this screen, the FBXL3/SCF axis represents a novel molecular pathway that regulates physiological levels of ATXN3 protein.
Slit/Robo signals prevent spinal motor neuron emigration by organizing the spinal cord basement membrane
Authors: Kim Minkyung , Lee Clare H , Barnum Sarah J , Watson Roland CJ , Li Jennifer , Mastick Grant S
Published: July 2019

The developing spinal cord builds a boundary between the CNS and the periphery, in the form of a basement membrane. The spinal cord basement membrane is a barrier that retains CNS neuron cell bodies, while being selectively permeable to specific axon types. Spinal motor neuron cell bodies are located in the ventral neural tube next to the floor plate and project their axons out through the basement membrane to peripheral targets. However, little is known about how spinal motor neuron cell bodies are retained inside the ventral neural tube, while their axons can exit. In previous work, we found that disruption of Slit/Robo signals caused motor neuron emigration outside the spinal cord. In the current study, we investigate how Slit/Robo signals are necessary to keep spinal motor neurons within the neural tube. Our findings show that when Slit/Robo signals were removed from motor neurons, they migrated outside the spinal cord. Furthermore, this emigration was associated with abnormal basement membrane protein expression in the ventral spinal cord. Using Robo2 and Slit2 conditional mutants, we found that motor neuron-derived Slit/Robo signals were required to set up a normal basement membrane in the spinal cord. Together, our results suggest that motor neurons produce Slit signals that are required for the basement membrane assembly to retain motor neuron cell bodies within the spinal cord.
A general strategy to develop cell permeable and fluorogenic probes for multi-colour nanoscopy
Authors: Wang Lu , Tran Mai , D’Este Elisa , Roberti Julia , Koch Birgit , Xue Lin , Johnsson Kai
Published: July 2019

Live-cell fluorescence nanoscopy is a powerful tool to study cellular biology on a molecular scale, yet its use is held back by the paucity of suitable fluorescent probes. Fluorescent probes based on regular fluorophores usually suffer from low cell permeability and unspecific background signal. We report a general strategy to transform regular fluorophores into fluorogenic probes with excellent cell permeability and low unspecific background signal. The strategy is based on the conversion of a carboxyl group found in rhodamines and related fluorophores into an electron-deficient amide. This conversion does not affect the spectroscopic properties of the fluorophore but permits it to exist in a dynamic equilibrium between two different forms: a fluorescent zwitterion and a non-fluorescent, cell permeable spirolactam. Probes based on such fluorophores generally are fluorogenic as the equilibrium shifts towards the fluorescent form when the probe binds to its cellular targets. The resulting increase in fluorescence can be up to 1000-fold. Using this simple design principle we created fluorogenic probes in various colours for different cellular targets for wash-free, multicolour, live-cell nanoscopy. The work establishes a general strategy to develop fluorogenic probes for live-cell bioimaging.
Ingestible Osmotic Pill for In-vivo Sampling of Gut Microbiome
Authors: Nejad Hojatollah Rezaei , Oliveira Bruno C. M. , Sadeqi Aydin , Dehkharghani Amin , Kondova Ivanela , Langermans Jan A.M. , Guasto Jeffrey S. , Tzipori Saul , Widmer Giovanni , Sonkusale Sameer R.
Published: July 2019

Technologies capable of non-invasively sampling different locations in the gut upstream of the colon will enable new insights into the role of organ-specific microbiota in human health. We present an ingestible, biocompatible, battery-less, 3D-printed micro-engineered pill with integrated osmotic sampler and microfluidic channels for in vivo sampling of the gut lumen and its microbiome upstream of the colon. The pill’s sampling performance was characterized using realistic in vitro models and validated in vivo in pigs and primates. Our results show that the bacterial populations recovered from the pills’ microfluidic channels closely resemble the bacterial population demographics of the microenvironment to which the pill was exposed. We believe such lab-on-a-pill devices will revolutionize our understanding of the spatial diversity of the gut microbiome and its response to medical conditions and treatments.
Decreased electrocortical temporal complexity distinguishes sleep from wakefulness
Authors: González Joaquín , Cavelli Matias , Mondino Alejandra , Pascovich Claudia , Castro-Zaballa Santiago , Torterolo Pablo , Rubido Nicolás
Published: July 2019

In most mammals, the sleep-wake cycle is constituted by three behavioral states: wakefulness (W), non-NREM (NREM) sleep, and REM sleep. These states are associated with drastic changes in cognitive capacities, mostly determined by the function of the thalamo-cortical system. The intra-cranial electroencephalogram or electocorticogram (ECoG), is an important tool for measuring the changes in the thalamo-cortical activity during W and sleep. In the present study we analyzed broad-band ECoG recordings of the rat by means of a time-series complexity measure that is easy to implement and robust to noise: the Permutation Entropy (PeEn). We found that PeEn is maximal during W and decreases during sleep. These results bring to light the different thalamo-cortical dynamics emerging during sleep-wake states, which are associated with the well-known spectral changes that occur when passing from W to sleep. Moreover, the PeEn analysis allows to determine behavioral states independently of the electrodes’ cortical location, which points to an underlying global pattern in the signal that differs among the cycle states that is missed by classical methods. Consequently, our data suggest that PeEn analysis of a single EEG channel could allow for cheap, easy, and efficient sleep monitoring.
Human POT1 Unfolds G-Quadruplexes by Conformational Selection
Authors: Chaires Jonathan B. , Gray Robert D. , Dean William L. , Monsen Robert , DeLeeuw Lynn W. , Stribinskis Vilius , Trent John O.
Published: July 2019

The reaction mechanism by which shelterin protein POT1 (ProtectionofTelomeres) unfolds human telomeric G-quadruplex structures is not fully understood. We report here kinetic, thermodynamic, hydrodynamic and computational studies that show that a conformational selection mechanism, in which POT1 binding is coupled to an obligatory unfolding reaction, is the most plausible mechanism. We show that binding of the single-strand oligonucleotide d[TTAGGGTTAG] to POT1 is fast, with an apparent relaxation time of 80.0 ± 0.4 ms, and strong, with a binding free energy of −10.1 ± 0.3 kcal mol−1. That favourable free energy arises from a large favourable enthalpy contribution of −38.2 ± 0.3 kcal mol−1. In sharp contrast, the binding of POT1 to an initially folded 24 nt G-quadruplex structure is slow, with an average relaxation time of 2000-3000 s. Fluorescence, circular dichroism and analytical ultracentrifugation studies show that POT1 binding is coupled to quadruplex unfolding with a final stoichiometry of 2 POT1 molecules bound per 24 nt DNA. The binding isotherm for the POT1-quadruplex binding interaction is sigmoidal, indicative of a complex reaction. A conformational selection model that includes equilibrium constants for both G-quadruplex unfolding and POT1 binding to the resultant single-strand provides an excellent quantitative fit to the experimental binding data. The overall favourable free energy of the POT1-quadruplex interaction is −7.1 kcal mol−1, which arises from a balance between unfavourable free energy of +3.4 kcal mol−1for quadruplex unfolding and a large, favorable free energy of −10.5 kcal mol−1for POT1 binding. We show that POT1 can unfold and bind to any conformational form of human telomeric G-quadruplex (antiparallel, hybrid or parallel), but will not interact with duplex DNA or with a parallel G-quadruplex structure formed by a c-myc promoter sequence. Finally, molecular dynamics simulations provide a detailed structural model of a 2:1 POT1:DNA complex that is fully consistent with experimental biophysical results.
Transcription factor NF-κB in a basal metazoan, the sponge, has conserved and unique sequences, activities, and regulation
Authors: Williams Leah M. , Inge Melissa M. , Mansfield Katelyn M. , Rasmussen Anna , Afghani Jamie , Agrba Mikhail , Albert Colleen , Andersson Cecilia , Babaei Milad , Babaei Mohammad , Bagdasaryants Abigail , Bonilla Arianna , Browne Amanda , Carpenter Sheldon , Chen Tiffany , Christie Blake , Cyr Andrew , Dam Katie , Dulock Nicholas , Erdene Galbadrakh , Esau Lindsie , Esonwune Stephanie , Hanchate Anvita , Huang Xinli , Jennings Timothy , Kasabwala Aarti , Kehoe Leanne , Kobayashi Ryan , Lee Migi , LeVan Andre , Liu Yuekun , Murphy Emily , Nambiar Avanti , Olive Meagan , Patel Devansh , Pavesi Flaminio , Petty Christopher A. , Samofalova Yelena , Sanchez Selma , Stejskal Camilla , Tang Yinian , Yapo Alia , Cleary John P. , Yunes Sarah A. , Siggers Trevor , Gilmore Thomas D.
Published: July 2019

Biological and biochemical functions of immunity transcription factor NF-κB in basal metazoans are largely unknown. Herein, we characterize transcription factor NF-κB from the demosponge Amphimedon queenslandica (Aq), in the phylum Porifera. Structurally and phylogenetically, the Aq-NF-κB protein is most similar to NF-κB p100 and p105 among vertebrate proteins, with an N-terminal DNA-binding/dimerization domain, a C-terminal Ankyrin (ANK) repeat domain, and a DNA binding-site profile more similar to human NF-κB proteins than Rel proteins. Aq-NF-κB also resembles the mammalian NF-κB protein p100 in that C-terminal truncation results in translocation of Aq-NF-κB to the nucleus and increases its transcriptional activation activity. Overexpression of a human or sea anemone IκB kinase (IKK) can induce C-terminal processing of Aq-NF-κB in vivo, and this processing requires C-terminal serine residues in Aq-NF-κB. Unlike human NF-κB p100, however, the C-terminal sequences of Aq-NF-κB do not effectively inhibit its DNA-binding activity when expressed in human cells. Tissue of another demosponge, a black encrusting sponge, contains NF-κB site DNA-binding activity and an NF-κB protein that appears mostly processed and in the nucleus of cells. NF-κB DNA-binding activity and processing is increased by treatment of sponge tissue with LPS. By transcriptomic analysis of A. queenslandica we identified likely homologs to many upstream NF-κB pathway components. These results present a functional characterization of the most ancient metazoan NF-κB protein to date, and show that many characteristics of mammalian NF-κB are conserved in sponge NF-κB, but the mechanism by which NF-κB functions and is regulated in the sponge may be somewhat different.
Topological stress is responsible for the detrimental outcomes of head-on replication-transcription conflicts
Authors: Lang Kevin S. , Merrikh Houra
Published: July 2019

Conflicts between the replication and transcription machineries have profound effects on chromosome duplication, genome organization, as well as evolution across species. Head-on conflicts (lagging strand genes) are significantly more detrimental than co-directional conflicts (leading strand genes). The source of this fundamental difference is unknown. Here, we report that topological stress underlies this difference. We find that head-on conflict resolution requires the relaxation of positive supercoils DNA gyrase and Topo IV. Interestingly, we find that after positive supercoil resolution, gyrase introduces excessive negative supercoils at head-on conflict regions, driving pervasive R-loop formation. The formation of these R-Loops through gyrase activity is most likely caused by the diffusion of negative supercoils through RNA polymerase spinning. Altogether, our results address a longstanding question regarding replication-transcription conflicts by revealing the fundamental mechanistic difference between the two types of encounters.
Salience network atrophy links neuron type-specific pathobiology to loss of empathy in frontotemporal dementia
Authors: Pasquini Lorenzo , Nana Alissa L. , Toller Gianina , Brown Jesse , Deng Jersey , Staffaroni Adam , Kim Eun-Joo , Hwang Ji-Hye L. , Li Libo , Park Youngsoon , Gaus Stephanie E. , Allen Isabel , Sturm Virginia E. , Spina Salvatore , Grinberg Lea T. , Rankin Katherine P. , Kramer Joel , Rosen Howard H. , Miller Bruce L. , Seeley William W.
Published: July 2019

Each neurodegenerative syndrome reflects a stereotyped pattern of cellular, regional, and large-scale brain network degeneration. In behavioral variant frontotemporal dementia (bvFTD), a disorder of social-emotional function, von Economo neurons (VENs) and fork cells are among the initial neuronal targets. These large layer 5 projection neurons are concentrated in the anterior cingulate and frontoinsular (FI) cortices, regions that anchor the salience network, a large-scale system linked to social-emotional function. Here, we studied patients with bvFTD, amyotrophic lateral sclerosis (ALS), or both, given that these syndromes share common pathobiological and genetic factors. Our goal was to determine how neuron type-specific TAR DNA-binding protein of 43 kDa (TDP-43) pathobiology relates to atrophy in specific brain structures and to loss of emotional empathy, a cardinal feature of bvFTD. We combined questionnaire-based empathy assessments, in vivo structural MR imaging, and quantitative histopathological data from 16 patients across the bvFTD/ALS spectrum. We show that TDP-43 pathobiology within right FI VENs and fork cells is associated with salience network atrophy spanning insular, medial frontal, and thalamic regions. Gray matter degeneration within these structures mediated loss of emotional empathy, suggesting a chain of influence linking the cellular, regional/network, and behavioral levels in producing signature bvFTD clinical features.
Associations of waking cortisol with DHEA and testosterone across the pubertal transition: Effects of threat-related early life stress
Authors: King Lucy S. , Graber Madelaine G. , Colich Natalie L. , Gotlib Ian H.
Published: July 2019

Atypical regulation of the hypothalamic-pituitary-adrenal (HPA) axis is a putative mechanism underlying the association between exposure to early life stress (ELS) and the subsequent development of mental and physical health difficulties. Recent research indicates that puberty is a period of HPA-axis plasticity during which the effects of exposure to ELS on cortisol regulation may change. In particular, increases in the sex hormones that drive pubertal maturation, including dehydroepiandrosterone (DHEA) and testosterone, may be implicated in pubertal recalibration of cortisol regulation. In the current study, we examined the associations among levels of objectively-rated threat-related ELS and salivary waking cortisol, DHEA, and testosterone in a sample of 178 adolescents (55% female) who were in early puberty at baseline (Tanner stages 1-3; mean Tanner stage[SD]=1.93[0.64]; mean age[SD]=11.42[1.04]) and were followed up approximately two years later (mean Tanner stage[SD]=3.46[0.86]; mean age[SD]=13.38[1.06]). Using multi-level modeling, we disaggregated the effects of between-individual levels and within-individual increases in pubertal stage and sex hormones on change in cortisol. Controlling for between-individual differences in average pubertal stage, the association between levels of cortisol and DHEA was more strongly positive among adolescents who evidenced greater within-individual increases in pubertal stage across time. Both higher average levels and greater within-individual increases in DHEA and testosterone were associated with increases in cortisol across time, indicating positive coupling of developmental changes in these hormones; however, coupling was attenuated in adolescents who were exposed to more severe threat-related ELS prior to puberty. These findings advance our understanding of the development of the HPA-axis and its association with childhood environmental risk during puberty.
A developmental gene regulatory network for invasive differentiation of theC. elegansanchor cell
Authors: Medwig-Kinney Taylor N. , Smith Jayson J. , Palmisano Nicholas J. , Tank Sujata , Zhang Wan , Matus David Q.
Published: July 2019

Cellular invasion is a key part of development, immunity, and disease. Using thein vivomodel ofC. elegansanchor cell invasion, we characterize the gene regulatory network that promotes invasive differentiation. The anchor cell is initially specified in a stochastic cell fate decision mediated by Notch signaling. Previous research has identified four conserved transcription factors,fos-1a(Fos),egl-43(EVI1/MEL),hlh-2(E/Daughterless) andnhr-67(NR2E1/TLX), that mediate anchor cell specification and/or invasive differentiation. Connections between these transcription factors and the underlying cell biology that they regulate is poorly understood. Here, using genome editing and RNA interference, we examine transcription factor interactions prior to and after anchor cell specification. During invasion we identify thategl-43,hlh-2, andnhr-67function together in a type I coherent feed-forward loop with positive feedback. Conversely, prior to specification, these transcription factors function independent of one another to regulate LIN-12 (Notch) activity. Together, these results demonstrate that, although the same transcription factors can function in fate specification and differentiated cell behavior, a gene regulatory network can be rapidly re-wired to reinforce a post-mitotic, pro-invasive state.

SUMMARY STATEMENT

Basement membrane invasion by theC. elegansanchor cell is coordinated by a dynamic gene regulatory network encompassing cell cycle dependent and independent sub-circuits.
Bacterial communities of herbivores and pollinators that have co-evolved Cucurbita spp
Authors: Shapiro Lori R. , Youngblom Madison , Scully Erin D. , Rocha Jorge , Paulson Joseph Nathaniel , Klepac-Ceraj Vanja , Cibrián-Jaramillo Angélica , López-Uribe Margarita M.
Published: July 2019

Insects, like all animals, are exposed to diverse environmental microbes throughout their life cycle. Yet, we know little about variation in the microbial communities associated with the majority of wild, unmanaged insect species. Here, we use a 16S rRNA gene metabarcoding approach to characterize temporal and geographic variation in the gut bacterial communities of herbivores (Acalymma vittatum and A. trivittatum) and pollinators (Eucera (Peponapis) pruinosa) that have co-evolved with the plant genus Cucurbita (pumpkin, squash, zucchini and gourds). Overall, we find high variability in the composition of bacterial communities in squash bees and beetles collected from different geographic locations and different time points throughout a growing season. Still, many of the most common OTUs are shared in E. (P.) pruinosa, A. vittatum and A. trivittatum. This suggests these insects may be exposed to similar environmental microbial sources while foraging on the same genus of host plants, and that similar microbial taxa may aid in digestion of Cucurbita plant material. The striped cucumber beetle A. vittatum can also transmit Erwinia tracheiphila, the causal agent of bacterial wilt of cucurbits. We find that few field-collected A. vittatum individuals have detectable E. tracheiphila, and when this plant pathogen is detected, it comprises less than 1% of the gut bacterial community. Together, these results are consistent with previous studies showing that plant feeding insects have highly variable gut bacterial communities, and provides a first step towards understanding the spatiotemporal variation in the microbial communities associated with herbivores and pollinators that depend on Cucurbita host plants.
Photosynthetic conversion of CO2to hyaluronic acid by engineered cyanobacteria
Authors: Zhang Lifang , Selão Tiago Toscano , Nixon Peter J. , Norling Birgitta
Published: July 2019

Hyaluronic acid (HA), consisting of alternating N-acetylglucosamine and glucuronic acid units, is a natural polymer with diverse cosmetic and medical applications. Currently, HA is produced by overexpressing HA synthases from gram-negativePasteurella multocida(encoded bypmHAS) or gram-positiveStreptococcus equisimilis(encoded byseHasA) in various heterotrophic microbial production platforms. Here we introduced these two different types of HA synthase into the fast-growing cyanobacteriumSynechococcussp. PCC 7002 (Syn7002) to explore the capacity for producing HA in a photosynthetic system. Our results show that both HA synthases enable Syn7002 to produce HA photoautotrophically, but that overexpression of the soluble HA synthase (PmHAS) is less deleterious to cell growth and results in higher production. Genetic disruption of the competing cellulose biosynthetic pathway increased the HA titer by over 5-fold (from 14 mg/L to 80 mg/L) and the relative proportion of HA with molecular mass greater than 2 MDa. Introduction ofglmSandglmU, coding for enzymes involved in the biosynthesis of the precursor UDP-N-acetylglucosamine, in combination with partial glycogen depletion, allowed photosynthetic production of 112 mg/L of HA in 5 days, an 8-fold increase in comparison to the initial PmHAS expressing strain. Addition oftuaDandgtaB(coding for genes involved in UDP-glucuronic acid biosynthesis) also improved the HA yield, albeit to a lesser extent. Overall our results have shown that cyanobacteria hold promise for sustainable production of pharmaceutically important polysaccharides from sunlight and CO2.
First Adaptation of Quinoa in the Bhutanese Mountain Agriculture Systems
Authors: Katwal Tirtha Bdr , Bazile Didier
Published: July 2019

Bhutan represents typical mountain agriculture farming systems with unique challenges. The topography, agriculture production systems and environmental constraints are typical of small-scale agricultural subsistence systems related to family farming in the Himalayan Mountains with very low level of mechanization, numerous abiotic stresses influenced by climate and other socio-economic constraints. Quinoa was first introduced in 2015 through FAO’s support to Bhutan as a new crop with the objectives to adapt this versatile crop to the local mountain agriculture conditions as a climate resilient crop for diversifying the farmer’s traditional potato, maize, and based cropping systems, and to enhance the food and nutritional security of the Bhutanese people.

Ten quinoa varieties were evaluated at two different sites representing contrasted mountain agro-ecologies in Bhutan and were tested during the two agricultural campaigns 2016 and 2017. Yusipang (2600 m asl) represents the cool temperate agroecological zone, and Lingmethang (640 m asl) the dry subtropical agroecological zone.The sowing time differed depending on the growing season and elevation of the sites. Results indicate that quinoa can be successfully grown in Bhutan for the two different agro-ecological zones. The grain yields varied from 0.61 to 2.68 t ha−1in the high altitude areas where quinoa was seeded in spring and harvested in autumn season. The grain yield in the lower elevation ranged from 1.59 to 2.98 t ha−1where the crop was sown in autumn and harvested in winter season. Depending on genotypes’ characteristics, agro-ecology and elevation of the sites and variety; crop maturity significantly varied from 92 to 197 days with all genotypes maturing much earlier in the lower elevations where mean minimum and maximum temperatures during the growing season were higher. Quinoa is rapidly promoted across different agro-ecological contexts in the country as a new climate resilient and nutrient dense pseudo cereal to diversify the traditional existing cropping system with some necessary adjustments in sowing time, suitable varieties and crop management practices. To fast track the rapid promotion of this new crop, four varieties have also been released in 2018. In just over three years, the cultivation of quinoa as a new cereal has been demonstrated and partially adapted to the maize-potato traditional cropping systems under the Himalayan mountain agriculture environment. Quinoa is also being adapted to the rice based cropping system and rapidly promoted as an alternative food security crop in the current 12thFive Year national development plan of Bhutan.
Longitudinal impact of oral probiotic Lactobacillus acidophilus vaccine strains on the immune response and gut microbiome of mice
Authors: Abdo Zaid , LeCureux Jonathan , LaVoy Alora , Eklund Bridget , Ryan Elizabeth , Dean Gregg
Published: July 2019

The potential role of probiotic bacteria as adjuvants in vaccine trials led to their use as nonparenteral live mucosal vaccine vectors. Yet, interactions between these vectors, the host and the microbiome are poorly understood. This study evaluates impact of three probiotic, Lactobacillus acidophilus, vector strains, and their interactions with the host’s immune response, on the gut microbiome. One strain expressed the membrane proximal external region from HIV-1 (MPER). The other two expressed MPER and either secreted interleukin-1β (IL-1β) or expressed the surface flagellin subunit C (FliC) as adjuvants. We also used MPER with rice bran as prebiotic supplement. We observed a strain dependent, differential effect suggesting that MPER and IL-1β induced a shift of the microbiome while FliC had minimal impact. Joint probiotic and prebiotic use resulted in a compound effect, highlighting a potential synbiotic approach to impact efficacy of vaccination. Careful consideration of constitutive adjuvants and use of prebiotics is needed depending on whether or not to target microbiome modulation to improve vaccine efficacy. No clear associations were observed between total or MPER-specific IgA and the microbiome suggesting a role for other immune mechanisms or a need to focus on IgA-bound, resident microbiota, most affected by an immune response.
Recovery of the type specimen ofAvena breviaristata, an endemic Algerian grass species collected only once (1882): morphology, taxonomy and botanical history
Authors: Gabriel Jennifer , Tkach Natalia , Röser Martin
Published: July 2019

Avena breviaristata, collected only once (1882) in Algeria and never re-collected since, is a very mysterious grass species because unfortunately even the type specimen got lost 60--80 years ago. Morphological information on this species was thus based on a few published descriptions, which made it difficult, however, to correctly infer the genus affiliation of this morphologically odd species.Avena breviaristatabecame affiliated in the past with various oat-like genera (Avenula,Helictotrichon,Tricholemma). Due to the recent rediscovery of the type specimen at the P herbarium and the opportunity to study this specimen, we report here on the morphological characters ofA. breviaristataunderpinned by meaningful illustrations. They are discussed in comparison with the morphology of representative species of the above-mentioned genera. Uncommon characters of the spikelets (type of disarticulation of the rachilla, lemma structure, lodicules) and to some extent of the inflorescences, leaves and leaf sheaths support the inclusion ofA. breviaristatain the North African genusTricholemma. Considering biogeography,T. breviaristatumfrom the arid Hauts Plateaux in Algeria is a highly xeromorphic counterpart of the mesomorphic speciesT. jahandiezii, which is confined to higher altitudes of the rather humid Moyen Atlas in Morocco. This underlines the status ofTricholemmaas a relic endemic. Our morphological survey supports the classification ofAvenula(onlyA. pubescens) as separate fromHelictotrichons.str. andHelictochloa. Moreover, morphological evidence does not support an origin ofA. pubescensby intergeneric hybridization between the latter genera as hypothesized in some prior studies. Especially the glabrous palea, the special shape of the lodicules and the structure of the awn show no intermediacy. The complicated history of the type collection ofT. breviaristatumand the role of botanical authors are given.
Anisotropic azimuthal surface‐wave inversion for a vertically fractured and transverse isotropy medium: Theory and examples from a controlled field experiment
Authors: Gofer Edan , Bachrach Ran
Published: July 2019

Fractures in elastic media add compliance to a rock in the direction normal to the fracture strike. Therefore, elastic wave velocities in a fractured rock will vary as a function of the energy propagation direction relative to the orientation of the aligned fracture set. Anisotropic Thomson–Haskell matrix Rayleigh‐wave equations for a vertically transverse isotropic media can be used to model surface‐wave dispersion along the principal axes of a vertically fractured and transversely isotropic medium. Furthermore, a workflow combining first‐break analysis and azimuthal anisotropic Rayleigh‐wave inversion can be used to estimate P‐wave and S‐wave velocities, Thomsen's ε, and Thomsen's δ along the principal axes of the orthorhombic symmetry. In this work, linear slip theory is used to map our inversion results to the equivalent vertically fractured and transversely isotropic medium coefficients. We carried out this inversion on a synthetic example and a field example. The synthetic data example results show that joint estimation of S‐wave velocities with Thomsen's parameters ε and δ along normal and parallel to the vertical fracture set is reliable and, when mapped to the corresponding vertically fractured and transversely isotropic medium, provides insight into the fracture compliances. When the inversion was carried out on the field data, results indicated that the fractured rock is more compliant in the azimuth normal to the visible fracture set orientation and that the in situ normal fracture compliance to tangential fracture compliance ratio is less than half, which implies some cementation may have occurred along the fractures. Such an observation has significant implications when modelling the transport properties of the rock and its strength. Both synthetic and field examples show the potential of azimuthal anisotropic Rayleigh‐wave inversion as the method can be further expanded to a more general case where the vertical fracture set orientation is not known a priori.
Environmental levels of neonicotinoids reduce prey consumption, mobility and emergence of the damselflyIschnura elegans
Authors: Barmentlo S. Henrik , Vriend Laura M. , van Grunsven Roy H. A. , Vijver Martina G.
Published: July 2019

Freshwaters are among the most endangered ecosystems in the world as a result of anthropogenic interference such as pollution. Pollution in the form of neonicotinoids has been intensively studied, but data thus far is often conflicted by contrasting responses between laboratory and field experiments. In addition, toxicity data are scarce and contradictory for insects such as Odonates (dragonflies and damselflies) and a potential risk to them may therefore be overlooked.

We investigate the potential risk of neonicotinoids to Odonates by exposing nymphs of the blue‐tailed damselflyIschnura elegansto environmentally relevant concentrations of the neonicotinoid thiacloprid. We considerI. elegansas an indicator species for other Odonates as it is an abundant, widespread and eurytopic species. We analyse the effects of thiacloprid on multiple endpoints (survival, consumption, growth, molting, mobility and emergence), using cage‐experiments as well as controlled field observations in naturally colonized experimental ditches. In addition, we assess sensitivity by either feeding the damselfly nymphs with lab‐cultured prey or by letting them feed freely on natural aquatic invertebrates.

All sublethal endpoints ofI. elegansare affected to some degree, and strongly depend on the food offered; free‐feeding nymphs are more sensitive than culture‐fed nymphs. Environmental relevant concentrations of thiacloprid strongly reduce the emergence ofI. elegansand this effect is more substantial in the natural populations compared to the caged damselflies. This is likely explained by exclusion of additional biotic pressures such as predation in the caged experiment.

Policy implications. Literature reports that one out of seven Odonates is threatened and 24% of the species have declining populations. Our observations show that current risks of neonicotinoids to Odonates are underestimated in laboratory experiments as the toxicity is governed by multiple biotic factors such as food quantity/quality and predation. Given the widespread abundance of blue‐tailed damselflyIschnura elegans, the observed sensitivity to neonicotinoids and current population trends of this species, these results indicate neonicotinoids play a central role in the Odonate decline in general.
Protecting juveniles, spawners or both: A practical statistical modelling approach for the design of marine protected areas
Authors: Grüss Arnaud , Biggs Christopher R. , Heyman William D. , Erisman Brad
Published: July 2019

Fish populations undertaking ontogenetic or spawning migrations pose challenges to marine protected area (MPA) planning because of the large extent of their distribution areas. There is a need to identify the juvenile and spawner hotspots of these populations that could be set aside as MPAs. Species distribution models making comprehensive use of available monitoring data and predicting the realized juvenile and spawner hotspots of migratory fish populations will assist resource managers with MPA planning.

We developed a statistical modelling approach relying on multiple, regional monitoring datasets for assisting spatial protection efforts targeting the juveniles, spawners, or both life stages, of migratory fish species and species complexes. This approach predicts juvenile and spawner hotspot indices, and critical life stage (CLS) hotspot indices, which integrate both juvenile and spawner hotspot indices. We applied the approach to 11 vulnerable species of the grouper–snapper complex of the U.S. Gulf of Mexico, which all form fish spawning aggregations (FSAs).

The CLS hotspot index was predicted to be highest in the Pulley Ridge and Flower Garden Banks areas, followed by the West Florida Shelf, southwestern Florida waters and portions of the Louisiana‐Mississippi‐Alabama shelf.

The Pulley Ridge Habitat Area of Particular Concern and Flower Garden Banks National Marine Sanctuary are two important existing MPAs of the U.S. Gulf of Mexico, whose possible expansion is being considered. The predicted CLS hotspot indices suggest that expanding these MPAs or increasing harvest regulations within them would offer substantial protection to both the juveniles and spawners of many FSA‐forming species of the grouper–snapper complex.

Synthesis and applications. As the number of marine protected areas (MPAs) continues to increase worldwide, statistical modelling approaches making comprehensive use of available data are urgently needed to support resource managers’ abilities to establish sound and efficient spatial protection plans. The outputs of our statistical models can serve as inputs to conservation planning software packages seeking optimal marine protected areas configurations or can be directly employed by resource managers for formulating spatial protection plans.
Systemic family therapy integrated with attachment interventions for adoptive families. Development of a treatment manual
Authors: Barbato Angelo , D’Avanzo Barbara , Vadilonga Francesco , Cortinovis Matteo , Lombardi Sara , Pili Francesca , Rangone Gloriana , Visconti Anna
Published: July 2019

Manualisation, although to some extent controversial, is an essential requirement for outcome research in family therapy. No manuals are available for therapy of adoptive families. This paper presents the development of a manual of a therapy model with adoptive families, based on the integration of a systems approach and attachment theory. We describe the background and process of development of the manual conducted in collaboration by clinicians and a research team. Twenty‐nine core elements of the model were identified and operationally defined by a focus group of clinicians. All elements except one showed good interrater reliability. The manual provides a tool to address the treatment of adopted families. Since the support to adoptive parents using a family therapy approach remains an under‐researched area, a manual available to clinicians and researchers will promote outcome studies in this area and training of therapists working with adoptive families.

Practitioner points

Adoptive parents often need help to form secure attachment bonds with their adopted children

A manual for family therapy targeted at adoptive families has been developed

The manual presents a model integrating attachment based interventions within a systemic framework
Emergency first aid readiness in Antarctica: Australian Antarctic expeditioners’ first aid credentials and self‐efficacy
Authors: Wallace Jan M , Harris Keith M , Stankovich Jim , Ayton Jeff , Bettiol Silvana S
Published: July 2019

Introduction

To help prevent future morbidity and mortality, this study examined Australian Antarctic expeditioners’ first aid credentials and self‐efficacy in providing emergency first aid in extreme environments.

Methods

A mixed method survey assessed Australian personnel working on Antarctic stations. Volunteer participants (n = 83) provided data on first aid training, self‐confidence of first aid readiness, and first aid preparations. The Extreme Conditions First Aid Confidence Scale (EC‐FACS) was developed and validated for this study. Multivariate analyses tested associations between first aid background, demographics and EC‐FACS. Open‐ended comments were subjected to thematic analysis.

Results

Over one‐third of participants did not hold current first aid certificates at expedition commencement. Factor analysis demonstrated the EC‐FACS was unidimensional, and internal consistency was high (α = 0.94), and showed first aid self‐efficacy was moderately high, but participants’ confidence decreased as first aid scenarios became more complex. Experience providing emergency first aid and level of first aid qualification were the strongest predictors of overall first aid self‐efficacy. Thematic analysis revealed expeditioners support higher first aid qualifications and want Antarctic‐specific wilderness first aid training.

Conclusions

These findings revealed that many Antarctic expeditioners may not be adequately prepared for first aid emergencies and have low confidence in handling complex medical situations. Based on these findings, we recommend higher first aid qualifications and training tailored to the Antarctic context. These modest steps can help prevent unnecessary and costly morbidity and mortality for extreme‐condition expeditioners.
Western Australia's Royalties for Regions program: a policy response to growth, regional neglect, and perceived disempowerment
Authors: van Staden Jan‐Willem , Haslam McKenzie Fiona
Published: July 2019

Under the right conditions, compounding socio‐political and economic change can dramatically alter government policy. From 2000, Western Australia, a resource‐rich jurisdiction, experienced significant change owing to a once‐in‐a‐generation resources boom, which forced a break with earlier development approaches. In 2008, regional interventionism returned to the State via the State Government's Royalties for Regions program. Departing from the neo‐liberal tradition, the program allocated 25 per cent of the State's royalty income to non‐metropolitan regions, over and above existing regional allocations, and its success remains disputed. While it is easy to question the program retrospectively, the socio‐economic and political circumstances from 2000 to 2008 reveal a “perfect storm” of conditions enabling the transition from neo‐liberalism to interventionism in regional development. This paper sets out to understand the multi‐faceted conditions that enabled the dramatic paradigm shift embodied by the program. To this end, it examines the State's rural–urban settlement dichotomy, its staples economy, and the policy context leading up to the program. Following that, the paper proposes a causal framework mapping out the factors driving and rationalising the program. These factors are then examined in detail and include perceived rural voter disenchantment, ineffectual regional development policy, the State's mining boom, inadequate regional development funding, the contrasting fortunes of two regions (illustrative of the impact of growth, and the lack thereof), and the political manoeuvring during the 2008 election. Finally, the paper concludes by considering how the conversion of these conditions resulted in the State's most significant regional policy redirection in decades.
The Comparison of Structural, Physicochemical, and Digestibility Properties of Repeatedly and Continuously Annealed Sweet Potato Starch
Authors: Zhang Bo , Wu Hao , Gou Min , Xu Meijuan , Liu Yu , Jing Luzhen , Zhao Kun , Jiang Hao , Li Wenhao
Published: July 2019

In order to investigate the varied effects of repeated annealing treatment (RANN) and continuous annealing treatment (CANN) on the structural, physicochemical, and digestibility properties of the sweet potato. The 75% starch‐water suspensions were prepared and incubated at 65 °C for 8 cycles and 96 hr. The results exhibited that RANN and CANN did not influence the starch granules and polarization cross obviously. The crystal type of RANN and CANN starches still maintained A‐type, while the relative crystallinity increased. The solubility, swelling power, peak viscosity and breakdown of RANN and CANN starches decreased, but the gelatinization transition temperatures, trough viscosity, final viscosity, setback, and pasting temperatures of starches increased after annealing treatments. Furthermore, RANN and CANN decreased the RS and RS + SDS contents with the increase of annealing cycles and time. The RANN was more effective in modification of the crystallinity, solubility, swelling power, pasting, gelatinization transition temperatures and enthalpy, and digestibility of starch before four times compared with the CANN ones. By and large, RANN may be a potential way for modification of structural, physicochemical and digestibility properties.

Practical Application

The described RANN and CANN starch provide new ideas for the study of modified starch. Furthermore, this study revealed the mechanism of annealing treatment and it was concluded that the repeated annealing treatment could provide a new potential way for the modification of starch.
Giant calcinosis revealing systemic sclerosis
Authors: Meriglier Etienne , Lafourcade François , Gombert Bruno , Landron Cedric
Published: July 2019

Calcinosis is a complication of systemic sclerosis, most often occurring more than several years after diagnosis. We report the case of a man who developed severe calcinosis in shoulders and hips occurring before other systemic sclerosis' symptoms.
PGC‐1a integrates a metabolism and growth network linked to caloric restriction
Authors: Miller Karl N. , Clark Josef P. , Martin Stephen A. , Howell Porsha R. , Burhans Maggie S. , Haws Spencer A. , Johnson Nathan B. , Rhoads Timothy W , Pavelec Derek M. , Eliceiri Kevin W. , Roopra Avtar S. , Ntambi James M. , Denu John M. , Parks Brian W. , Anderson Rozalyn M.
Published: July 2019

Deleterious changes in energy metabolism have been linked to aging and disease vulnerability, while activation of mitochondrial pathways has been linked to delayed aging by caloric restriction (CR). The basis for these associations is poorly understood, and the scope of impact of mitochondrial activation on cellular function has yet to be defined. Here, we show that mitochondrial regulator PGC‐1a is induced by CR in multiple tissues, and at the cellular level, CR‐like activation of PGC‐1a impacts a network that integrates mitochondrial status with metabolism and growth parameters. Transcriptional profiling reveals that diverse functions, including immune pathways, growth, structure, and macromolecule homeostasis, are responsive to PGC‐1a. Mechanistically, these changes in gene expression were linked to chromatin remodeling and RNA processing. Metabolic changes implicated in the transcriptional data were confirmed functionally including shifts in NAD metabolism, lipid metabolism, and membrane lipid composition. Delayed cellular proliferation, altered cytoskeleton, and attenuated growth signaling through post‐transcriptional and post‐translational mechanisms were also identified as outcomes of PGC‐1a‐directed mitochondrial activation. Furthermore, in vivo in tissues from a genetically heterogeneous mouse population, endogenous PGC‐1a expression was correlated with this same metabolism and growth network. These data show that small changes in metabolism have broad consequences that arguably would profoundly alter cell function. We suggest that this PGC‐1a sensitive network may be the basis for the association between mitochondrial function and aging where small deficiencies precipitate loss of function across a spectrum of cellular activities.