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Abstract The asymptotic symmetry group of general relativity in asymptotically flat spacetimes can be extended from the Bondi-Metzner-Sachs (BMS) group to the generalized BMS (GMBS) group suggested by Campiglia and Laddha, which includes arbitrary diffeomorphisms of the celestial two-sphere. It can be further extended to the Weyl BMS (BMSW) group suggested by Freidel, Oliveri, Pranzetti and Speziale, which includes general conformal transformations. We compute the action of fully nonlinear BMSW transformations on the leading order Bondi-gauge metric functions: specifically, the induced metric, Bondi mass aspect, angular momentum aspect, and shear. These results generalize previous linearized results in the BMSW context by Freidel et al., and also nonlinear results in the BMS context by Chen, Wang, Wang and Yau. The transformation laws will be useful for exploring implications of the BMSW group.

Background:. Nerve reconstruction techniques for lumbosacral plexus (LSP) injuries vary. There are no clear treatment guidelines available, and summative evaluations of the literature discussing these surgeries are lacking. For these reasons, this investigation aimed to systematically review and consolidate all available literature discussing surgical interventions for LSP injuries and cohesively present patient-reported and objective postoperative outcomes. Methods:. The authors conducted a systematic review using PubMed, Embase, Web of Science, ProQuest Dissertations and Theses Global (via Proquest.com), and ClinicalTrials.gov databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. After title and abstract screening, identified articles were read in full and selected for inclusion based on prespecified criteria. Results:. Our literature search identified 8683 potential citations, and after duplicate removal, abstract screening, and full-text review, 62 studies remained meeting inclusion and exclusion criteria. Outcomes were extracted according to the location of injury and type of surgical repair. Injuries were classified into isolated femoral nerve injuries, isolated obturator nerve injuries, isolated sciatic nerve injuries, and multilevel LSP injuries. Surgical treatment was further classified into exploration with neurolysis, direct repair, nerve grafting, and nerve transfer surgery. Conclusions:. Although results vary based on the location of the injury and the surgical technique used, nerve grafts and transfers demonstrated reasonable success in improving functional and pain outcomes. Overall, isolated femoral and obturator nerve injuries had the best outcomes reported with surgical treatment. Furthermore, incomplete sciatic nerve and multilevel LSP injuries had more reported surgical options and better outcomes than complete sciatic nerve injuries.

Summary:. New developments in targeted muscle reinnervation promise better options for treatment of neuropathic pain and improved prosthetic control. For transhumeral amputations, the traditional approach involves an anterior incision to access the median and ulnar nerves and a second posterior incision to access the radial nerve. This is necessitated as exposure of motor branches of the radial nerve distal to the branch to the long head of the triceps is difficult from the anterior approach. Herein, we describe a technique for transferring the radial nerve proper distal to the long head branch to a motor branch to the medial or lateral head of the triceps through internal neurolysis and fascicular transfer. This allows all surgical steps to be performed through a single incision while preserving native motor branches to the biceps and triceps muscles.

At first glance, it appears there is little difference between the molecular structures of methylenedioxymethamphetamine (MDMA), which has an N-methyl attached to its amino group, and methylenedioxyamphetamine (MDA), a primary amine that is recognized to have hallucinogenic activity. It is known from studies with other hallucinogenic amphetamines that N-methylation of hallucinogenic amphetamines attenuates or abolishes hallucinogenic activity. Nevertheless, MDMA is biologically active and has a potency only slightly less than its MDA parent. Importantly, it is the Ievo-isomer of hallucinogenic phenethylamines that is more biologically active, whereas it is the dextro isomer of MDMA that is more active. This reversal of stereochemistry for the activity of two very closely related molecules is a very powerful clue that their mechanisms of action differ. Finally, extension of the alpha-methyl of hallucinogenic amphetamines to an alpha-ethyl moiety completely abolishes their hallucinogenic activity. Ultimately, we extended the alpha-methyl group of MDMA to an alpha-ethyl to afford a molecule we named (N-Methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB) that retained significant MDMA-like psychoactivity. Hence, there are three structural features that distinguish MDMA from the hallucinogenic amphetamines: (1) the N-methyl on the basic nitrogen, (2) the reversal of stereochemistry and, (3) tolerance of an alpha-ethyl moiety as contrasted with the alpha-methyl of hallucinogenic phenethylamines. Clearly, MDMA is distinct from classical hallucinogenic phenethylamines in its structure, and its psychopharmacology is also unique. Thus, in 1986 I proposed the name “Entactogen” for the pharmacological class of drugs that includes 3,4-methylenedioxymethamphetamine (MDMA) and other substances with a similar psychopharmacological effect. The name is derived from roots that indicate that entactogens produce a “touching within.” Rather than having significant psychostimulant, or hallucinogenic effects, MDMA powerfully promotes affiliative social behavior, has acute anxiolytic effects, and can lead to profound states of introspection and personal reflection. Its mechanism of action is now established as involving transport of MDMA by the neuronal serotonin reuptake carrier followed by carrier-mediated release of stored neuronal serotonin.

Global crop production rate has exceeded the availability of pollination services provided by managed honeybees, and habitat loss remains a key factor in the loss of wild pollinators. Revegetation of agricultural land and wild pollination may provide a solution; however, the collection of floral trait data that are correlated to pollinator preferences remains an under studied and complex process. Here, we demonstrate a method for scent analysis, ordination [non-metric dimensional scaling (NMDS)], and clustering outputs that provides a fast and reproducible procedure for a broad grouping of flora based on scent and unlocking characteristic inter-floral patterns. We report the floral profiles of 15 unstudied native Australian plant species and the extent to which they match the commonly cultivated seed crops of Daucus carota L and Brassica rapa L. Through solid-phase microextraction (SPME) paired with gas chromatography–mass spectrometry (GC-MS), we identify a set of inter-family shared, common floral volatiles from these plant species as well as unique and characteristic patterns.

Inhaled antibiotics control chronic airway infection and maintain respiratory health in cystic fibrosis (CF). Given variation in patient responses to inhaled antibiotics, the ability to identify distinct responder phenotypes would facilitate the delivery of personalized care. Previously, a 10-gene panel was identified, measured directly from blood leukocytes, which predicted host response to intravenous antibiotic treatment during pulmonary exacerbations. In the current study, we tested whether the same panel predicted clinical response in subjects receiving a month of inhaled antibiotic therapy with aztreonam lysine (AZLI; Cayston®). A small cohort of CF subjects infected with Pseudomonas aeruginosa were enrolled at baseline health, prior to initiating one month's treatment with AZLI using the Altera® nebulizer system. Eighteen CF subjects underwent blood leukocyte gene panel measurements, sputum quantitative microbiology, spirometry, and C-reactive protein (CRP) measurement prior to onset and at completion of 4 weeks of AZLI therapy. Mean absolute improvement in percent predicted Forced Expiratory Volume in one second (ppFEV1) was 3%. Significant reductions in sputum bacterial colony counts were detected with treatment. CRP increased following treatment. While single genes within the panel did not change significantly following treatment, the analysis of multigene panel data demonstrated that HCA112 gene predicted ppFEV1 improvement. Hierarchical clustering based on gene expression yielded two distinctive molecular clusters before and after AZLI therapy. In conclusion, peripheral blood leukocyte genes quantifying inflammation are associated with responses to inhaled antibiotic therapy. Molecular quantification of systemic inflammation may indicate subgroups of CF subjects with variations in underlying inflammation and with variable clinical responses to inhaled antibiotics. Given the size limitation of the study, larger studies are needed in order to evaluate whether molecular measures may add precision to the determination of infectious and inflammatory outcomes following courses of inhaled antimicrobial therapies. Clinical Trials.gov Identifier: NCT01736839.

Globally, both managed and wild pollination services are unable to meet current rates of crop production and pollination demand. Wild pollination services could be improved through the reforestation of agricultural land margins, however plant–pollinator networks remain poorly understood and the collection of key floral traits a complex process. Herein, we consider the merits of pollen as a floral trait and the application of a rapid pollen comparison method in assessing whether pollen traits are conserved at a taxonomic level. Reporting the previously unstudied, pollen fingerprints of 18 Australian plant species, these are compared against the seed crop Daucus carota L. and two naturalised Brassica hybrids. Applying atmospheric solids analysis probe mass spectrometry (ASAP-MS) for rapid pollen fingerprinting, pollens are compared through non-metric multidimensional scaling (NMDS), Jaccard index correlation and hierarchical clustering. Demonstrating the merits of this analytical method for the grouping of potential revegetation flora, we identify key pollen similarities and differences that could correlate with wild pollinator preferences.

Citrus bioflavonoids are polyphenolic plant-derived pigments found in high levels in oranges, lemons, grapefruits and other citrus fruits. The three most abundant types of citrus bioflavonoids are hesperidin, naringenin and eriocitrin. Citrus bioflavonoids have long been known to possess powerful free radical-scavenging properties and cardioprotective effects. The study involved the analysis of 10 commercially available citrus bioflavonoid supplements from three different countries: Australia, the United States and Canada. The supplements were tested for their citrus bioflavonoid content which varied from 0.8 to 33.3% w/w. The daily bioflavonoid dose varied from 19 mg to 560 mg. Hesperidin was the major citrus bioflavonoid in nine out of ten supplements. One supplement was found to contain less than 10% of the quantity of rutin claimed to have been added. The DPP-4 inhibitory potential, compared through an estimation of rutin equivalence, ranged from 1.9 mg to 400 mg per day. This data highlights the variability between the supplements in their potential to inhibit DPP-4 for subsequent health benefits.

For soilborne pathogens, germination of the resting or dormant propagule that enables persistence within the soil environment is a key point in pathogenesis. Spongospora subterranea is an obligate soilborne protozoan that infects the roots and tubers of potato causing root and powdery scab disease for which there are currently no effective controls. A better understanding of the molecular basis of resting spore germination of S. subterranea could be important for development of novel disease interventions. However, as an obligate biotroph and soil dwelling organism, the application of new omics techniques for the study of the pre-infection process in S. subterranea has been problematic. Here, RNA sequencing was used to analyse the reprogramming of S. subterranea resting spores during the transition to zoospores in an in-vitro model. More than 63 million mean high-quality reads per sample were generated from the resting and germinating spores. By using a combination of reference-based and de novo transcriptome assembly, 6,664 unigenes were identified. The identified unigenes were subsequently annotated based on known proteins using BLAST search. Of 5,448 annotated genes, 570 genes were identified to be differentially expressed during the germination of S. subterranea resting spores, with most of the significant genes belonging to transcription and translation, amino acids biosynthesis, transport, energy metabolic processes, fatty acid metabolism, stress response and DNA repair. The datasets generated in this study provide a basic knowledge of the physiological processes associated with spore germination and will facilitate functional predictions of novel genes in S. subterranea and other plasmodiophorids. We introduce several candidate genes related to the germination of an obligate biotrophic soilborne pathogen which could be applied to the development of antimicrobial agents for soil inoculum management.

This study documents the development of a new MMPI-2 scale, Hopelessness (Hp), designed to identify suicide risk in examinees who, for whatever reason, may be reluctant to endorse items reflecting explicit suicide content. The psychometric and empirical validity characteristics were examined in a sample of 153 Italian psychiatric inpatients, all of whom were administered the MMPI-2, the Beck Hopelessness Scale (BHS), and the Mini International Neuropsychiatric Interview (MINI) shortly following admission.Item analysis suggested that the removal of one of the twelve original Hp items enhanced homogeneity of the scale and Bayesian confirmatory factor analysis (BCFA) indicated the fit of a unidimensional model (PPPs = 0.50 [PPC = -36.42/37.07]) for the 11-item version, with adequate reliability (ordinal alpha = 0.86). A regression analysis, with the MINI scores as criterion, and Hp and BHS scores as independent variables, indicated that only Hp scores (beta = 0.25, t = 2.32, p < 0.05) were independently associated with the MINI suicide risk. These findings indicate that the MMPI-2 Hp scale may be considered a valid and potentially useful measure of pessimistic attitudes toward the future and of potential suicide risk.

The red fox is a highly adaptable mammal that has established itself world-wide in many different environments. Contributing to its success is a social structure based on chemical signalling between individuals. Urine scent marking behaviour has long been known in foxes, but there has not been a recent study of the chemical composition of fox urine. We have used solid-phase microextraction and gas chromatography-mass spectrometry to analyze the urinary volatiles in 15 free-ranging wild foxes (2 female) living in farmlands and bush in Victoria, Australia. Foxes here are routinely culled as feral pests, and the urine was collected by bladder puncture soon after death. Compounds were identified from their mass spectra and Kovats retention indices. There were 53 possible endogenous scent compounds, 10 plant-derived compounds and 5 anthropogenic xenobiotics. Among the plant chemicals were several aromatic apocarotenoids previously found in greater abundance in the fox tail gland. They reflect the dietary consumption of carotenoids, essential for optimal health. One third of all the endogenous volatiles were sulfur compounds, a highly odiferous group which included thiols, methylsulfides and polysulfides. Five of the sulfur compounds (3-isopentenyl thiol, 1- and 2-phenylethyl methyl sulfide, octanethiol and benzyl methyl sulfide) have only been found in foxes, and four others (isopentyl methyl sulfide, 3-isopentenyl methyl sulfide, and 1- and 2-phenylethane thiol) only in some canid, mink and skunk species. This indicates that they are not normal mammalian metabolites and have evolved to serve a specific role. This role is for defence in musteloids and most likely for chemical communication in canids. The total production of sulfur compounds varied greatly between foxes (median 1.2, range 0.4-32.3 μg 'acetophenone equivalents'/mg creatinine) as did the relative abundance of different chemical types. The urinary scent chemistry may represent a highly evolved system of semiochemicals for communication between foxes.

Chemical dormancy breakers are often used to manipulate floral bud break in sweet cherry production, and their use is increasing due to unpredictable climate effects. The role of plant hormones in regulating the critical transition of floral buds from dormant to opening in deciduous trees is now emerging. By monitoring changes in endogenous hormone levels within floral buds that are undergoing the transition from dormant to the growing state in response to various cues (environmental and/or chemical inducers), we can begin to distinguish the plant hormones that are the drivers of this process. This study sought to identify key hormonal regulators of floral bud break using sweet cherry as a model and modifying timing of bud break through the application of two chemical dormancy breakers, hydrogen cyanamide (HC, Dormex®) and emulsified vegetable oil compound (EVOC, Waiken®), and to determine the effect of these chemicals on fruit growth and quality. Treatments were applied at label rates 35–40 days before estimated bud break. We found that HC-treated tree buds broke earlier, and this was associated with a significant early elevation of the cytokinins dihydrozeatin and dihydrozeatin riboside compared to the control and EVOC-treated tree buds. In contrast, changes in auxin and abscisic acid content did not appear to explain the hastened bud burst induced by hydrogen cyanamide. While HC-treated trees resulted in larger fruit, there was a higher incidence of cracked fruit and the pack-out of A-grade fruit was reduced. The increase in fruit size was attributed to the earlier flowering and hence longer growing period. Harvest assessment of fruit quality showed no treatment effect on most quality parameters, including fruit dry matter content, total soluble solids or malic acid content, but a reduction in fruit compression firmness and stem pull force in EVOC-treated trees was observed. However, all fruit still met the Australian industry fruit quality export market standards. This study offers important insights into bud hormonal activities underpinning the action of these chemical regulators; understanding bud responses is critically important to ensuring consistent and sustainable fruit tree production systems into the future. It also demonstrates that the dormancy-breaking agents HC and EVOC have no detrimental impact on fruit quality at harvest or following storage, however growers need to be aware of the potential for increased fruit cracking when earlier bud break results in a longer growing season which has the potential to increase fruit size. Further studies are required to determine the role of gibberellin in hastening bud break by dormancy breakers.

The interaction between plants and pathogenic microorganisms is a multifaceted process mediated by both plant- and pathogen-derived molecules, including proteins, metabolites, and lipids. Large-scale proteome analysis can quantify the dynamics of proteins, biological pathways, and posttranslational modifications (PTMs) involved in the plant–pathogen interaction. Mass spectrometry (MS)-based proteomics has become the preferred method for characterizing proteins at the proteome and sub-proteome (e.g., the phosphoproteome) levels. MS-based proteomics can reveal changes in the quantitative state of a proteome and provide a foundation for understanding the mechanisms involved in plant–pathogen interactions. This review is intended as a primer for biologists that may be unfamiliar with the diverse range of methodology for MS-based shotgun proteomics, with a focus on techniques that have been used to investigate plant–pathogen interactions. We provide a summary of the essential steps required for shotgun proteomic studies of plants, pathogens and plant–pathogen interactions, including methods for protein digestion, identification, separation, and quantification. Finally, we discuss how protein PTMs may directly participate in the interaction between a pathogen and its host plant.

Some aspects of the brain change volume at a fairly constant rate across the life span, i.e., linear maturation rate with respect to age, whereas other aspects of the brain change volume at different rates for younger vs. older age ranges, i.e., non-linear changes. Various forms of non-linear maturation likely reflect different biological mechanisms such that theoretical distinctions between maturation patterns ought to be considered. Simulated data with known maturation patterns and a single critical age characterizing a qualitative change in maturation were used to establish the validity of a non-parametric fitting method, the smoothing spline, combined with processing steps for determining the form of the pattern and the associated critical age. Multiple classes of models were assessed, including model-free, bottom up approaches. Three categories of maturation patterns were explored: U-shaped, with a change in direction; sigmoidal, with an isolated period of change; accelerating, with changes in amplitude but not direction. As noise is a limiting factor in curve fitting, smoothing splines were fit to data with idealized low and realistic noise levels. The smoothing spline was shown to contain the relevant information to extract the critical ages of all maturation patterns in the form of derivative zero points, but the previously proposed method of using third derivative zero points worked only for the accelerating category. Therefore, an additional classification step was included to first determine the category of maturation pattern. Classification accuracy and identification of the calculated critical age within 5 years of the actual critical age was found to be perfect for low noise and high for realistic noise levels. To demonstrate the applicability of the method, a reevaluation of published biological data previously analyzed using third derivative zero points to determine critical ages was carried out for 17 aspects of MRI scans from 1,100 subjects. For a majority of non-linear areas, new critical ages were identified. Further modifications to the analysis procedure could include a wider set of maturation patterns and the inclusion of multiple critical ages to help determine distinctions between brain areas in the timing of developmental or degenerative events that influence their volume.

There is a lack of current research to support the efficacy of a combination of equine-assisted activities (EAA) and brain building activities to influence motor skill competencies in youth with neurodevelopmental disorders (ND). The primary objective of this study was to quantify changes in motor skill proficiency before and after 8 weeks of EAA and brain-building activities in youth with ND. A secondary objective was to quantify changes in motor skill proficiency before and after 1 year of EAA and brain-building activities in youth with ND. Twenty-five youth completed the same 32-week protocol that was separated into 4, 8-week blocks, in the following order: (1) control; (2) EAA-only; (3) washout; (4) GaitWay block (EAA and brain building activities). Before and after each block, motor skills were assessed using the Short Form of the Bruininks-Oseretsky Test of Motor Proficiency-Version 2 (BOT-2). Seven youth continued with the GaitWay intervention for one additional year, and the BOT-2 Short Form was also administered following this intervention. A repeated-measures analysis-of-variance was performed to compare BOT-2 subtest and overall scores between interventions with a significance of 0.05. Manual dexterity was higher at Post-Washout [3.3 (2.4)] vs. Pre-Control [2.2 (2.1); p = 0.018] and Post-Control [2.6 (2.0); p = 0.024], and at Post-GaitWay vs. Pre-Control [3.2 (2.4) vs. 2.2 (2.1); p = 0.037]. Upper-limb coordination was higher at Post-GaitWay vs. Post-Control [6.0 (4.1) vs. 3.9 (3.8); p = 0.050]. When compared to Pre-Control [3.2 (3.0)], strength was higher at Post-EAA [4.9 (3.5); p = 0.028] and at Post-GaitWay [5.2 (2.9); p = 0.015]. Overall scores were higher at Post-GaitWay [39.1 (22.2)] when compared to Pre-Control [32.4 (21.6); p = 0.003] and Post-Control [32.5 (21.9); p = 0.009]. Additionally, motor skills were maintained for 1 year following the Post-GaitWay testing session among seven participants. This is the first known study to include and demonstrate the short-term and long-term effects of a combination of EAA and brain building activities with motor proficiency in youth with ND.Clinical Trial Registration: Motor Skill Proficiency After Equine-Assisted Activities and Brain-building Tasks; www.ClinicalTrials.gov, identifier: NCT04158960.

Spongospora subterranea is an obligate biotrophic pathogen, causing substantial economic loss to potato industries globally. Currently, there are no fully effective management strategies for the control of potato diseases caused by S. subterranea. To further our understanding of S. subterranea biology during infection, we characterized the transcriptome and proteome of the pathogen during the invasion of roots of a susceptible and a resistant potato cultivar. A total of 7650 transcripts from S. subterranea were identified in the transcriptome analysis in which 1377 transcripts were differentially expressed between two cultivars. In proteome analysis, we identified 117 proteins with 42 proteins significantly changed in comparisons between resistant and susceptible cultivars. The functional annotation of transcriptome data indicated that the gene ontology terms related to the transportation and actin processes were induced in the resistant cultivar. The downregulation of enzyme activity and nucleic acid metabolism in the resistant cultivar suggests a probable influence of these processes in the virulence of S. subterranea. The protein analysis results indicated that the majority of differentially expressed proteins were related to the metabolic processes and transporter activity. The present study provides a comprehensive molecular insight into the multiple layers of gene regulation that contribute to S. subterranea infection and development in planta and illuminates the role of host immunity in affecting pathogen responses.