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Potassium (K) nutrition and drought stress affect soybean (Glycine max (L.) Merr.) vigor and productivity through the combined impacts on water regulation. A study was conducted with soybean grown in 18.9‐L buckets under a rain out shelter to determine how the interaction between these crop stresses at various growth stages influences the crop leaf K concentration, biomass production, total K uptake (TKU), grain yield, and temperature of the uppermost fully expanded trifoliate. Treatments included soybean grown with and without preplant fertilizer K, soil moisture at 50% (drought) or 80% (well‐watered) field capacity, imposed drought during vegetative growth (V3–V7), flowering (R1–R3), pod development (R4–early R6), and seed development (R5–mid‐R6) on two different silt loam soils. Widespread K deficiencies were observed during the study across all treatments. Drought stress significantly (p < 0.05) reduced the TKU, aboveground biomass production, and grain yield. The crop growth stage when drought stress was imposed was a significant factor, with greater reductions in plant response parameters when stress was imposed during reproductive growth. Preplant fertilizer K increased trifoliolate K concentrations and TKU in drought conditions, but did not increase the grain yield of well‐watered soybean. Leaf temperature increased when under drought stress compared to well‐watered soybean (p < 0.0001) but the impact of crop K nutrition status on leaf temperature was inconclusive because of widespread K deficiencies. Results emphasize the complexity of the interactions between K nutrition and drought stress in soybean, as drought stress impeded K uptake, exacerbated K deficiencies, and limited yield. Core Ideas: Drought stress exacerbated the impacts of K deficiency in soybean.Leaf temperature increased when under drought stress across growth stages but was inconclusive when K deficient.Total K uptake and biomass production are affected by both K availability and drought stress across growth stages.Drought stress during reproductive stages reduces total K uptake, biomass, and grain yield to a greater degree. [ABSTRACT FROM AUTHOR]

Antibodies have proven highly valuable for therapeutic development; however, they are typically poor candidates for applications that require activation of G protein‐coupled receptors (GPCRs), the largest collection of targets for clinically approved drugs. Nanobodies (Nbs), the smallest antibody fragments retaining full antigen‐binding capacity, have emerged as promising tools for pharmacologic applications, including GPCR modulation. Past work has shown that conjugation of Nbs with ligands can provide GPCR agonists that exhibit improved activity and selectivity compared to their parent ligands. The neurokinin‐1 receptor (NK1R), a GPCR targeted for the treatment of pain, is activated by peptide agonists such as Substance P (SP) and neurokinin A (NKA), which induce signaling through multiple pathways (Gs, Gq and β‐arrestin). In this study, we investigated whether conjugating NK1R ligands with Nbs that bind to a separate location on the receptor would provide chimeric compounds with distinctive signaling properties. We employed sortase A‐mediated ligation to generate several conjugates consisting of Nbs linked to NK1R ligands. Many of these conjugates exhibited divergent and unexpected signaling properties and transcriptional outputs. For example, some Nb‐NKA conjugates showed enhanced receptor binding capacity, high potency partial agonism, prolonged cAMP production, and an increase in transcriptional output associated with Gs signaling; whereas other conjugates were virtually inactive. Nanobody conjugation caused only minor alterations in ligand‐induced upstream Gq signaling with unexpected enhancements in transcriptional (downstream) responses. Our findings underscore the potential of nanobody conjugation for providing compounds with advantageous properties such as biased agonism, prolonged duration of action, and enhanced transcriptional responses. These compounds hold promise not only for facilitating fundamental research on GPCR signal transduction mechanisms but also for the development of more potent and enduring therapeutics. [ABSTRACT FROM AUTHOR]

Vaccination is considered one of the major milestones in modern medicine, facilitating the control and eradication of life‐threatening infectious diseases. Vaccine adjuvants are a key component of many vaccines, serving to steer antigen‐specific immune responses and increase their magnitude. Despite major advances in the field of adjuvant research over recent decades, our understanding of their mechanism of action remains incomplete. This hinders our capacity to further improve these adjuvant technologies, so addressing how adjuvants induce and control the induction of innate and adaptive immunity is a priority. Investigating how adjuvant physicochemical properties, such as size and charge, exert immunomodulatory effects can provide valuable insights and serve as the foundation for the rational design of vaccine adjuvants. Most clinically applied adjuvants are particulate in nature and polymeric particulate adjuvants present advantages due to stability, biocompatibility profiles, and flexibility in terms of formulation. These properties can impact on antigen release kinetics and biodistribution, cellular uptake and targeting, and drainage to the lymphatics, consequently dictating the induction of innate, cellular, and humoral adaptive immunity. A current focus is to apply rational design principles to the development of adjuvants capable of eliciting robust cellular immune responses including CD8+ cytotoxic T‐cell and Th1‐biased CD4+ T‐cell responses, which are required for vaccines against intracellular pathogens and cancer. This review highlights recent advances in our understanding of how particulate adjuvants, especially polymer‐based particulates, modulate immune responses and how this can be used as a guide for improved adjuvant design. [ABSTRACT FROM AUTHOR]

The spatial variability of soybean [Glycine max (L.) Merr.] leaf‐K (potassium) concentrations must be considered when collecting samples to monitor crop K status. Five commercial soybean fields were sampled at a 0.4‐ha grid resolution at two reproductive growth stages to quantify the trifoliolate tissue‐K concentration. The objectives of this study were to identify the potential field variability of soybean leaf‐K concentrations in typical Mid‐south US soybean production fields, evaluate interpolation methods, and develop a sampling protocol for in‐season soybean tissue monitoring. No consistent spatial dependencies were found in the leaf‐K concentrations across the fields and sample times, indicating that a soybean tissue‐K grid sampling protocol cannot be generalized to a specific area size. Inverse distance weighted (IDW) and rasterization interpolation methods were considered to predict leaf‐K concentrations between the sampled grid points at grid resolutions ranging from 0.4 to 4 ha. The IDW method consistently predicted leaf‐K concentrations between the known values with less error than rasterization. Rather than grid sampling, composite leaf samples should be collected based on management zones to provide a simplified sampling protocol. Within each management zone, a composite sample must consist of uppermost fully expanded trifoliolate leaves collected from at least 18 locations to ensure that the sample measures within the 95% confidence interval of the area average leaf‐K concentration. The developed sampling protocol coupled with the dynamic critical tissue‐K concentration curve will provide producers with the ability to effectively monitor soybean for potential hidden hunger and verify K deficiency symptoms in season. Core Ideas: Soybean leaf‐K (potassium) concentration was not consistently spatially autocorrelated at 0.4‐ha grid resolutions.Inverse distance weighted interpolation consistently predicted leaf‐K values with less error than rasterization.One composite sample should include leaves collected from at least 18 points within the area of interest.Soybean leaf samples should be collected based on management zones to monitor leaf‐K concentrations. [ABSTRACT FROM AUTHOR]

Genetic identity analysis and PIT (passive integrated transponder) tagging were used to examine the freshwater return rates and phenotypic characteristics of n = 1791 downstream migrating juvenile Salmo trutta in the Burrishoole catchment (northwest Ireland) across the period September 2017 to December 2020. In this system, juveniles out‐migrate (move from freshwater into brackish or marine habitats) in every month of the year, with distinct seasonal peaks in spring (March through June; mostly silvered smolts) and autumn (September through December; mostly younger, unsilvered fry or parr). Both types exhibited a sex‐bias towards females, which was stronger in spring (78% females) than in autumn outmigrants (67%). Sixty‐nine returning fish were matched back to previous juvenile outmigrants, and similar return rates were found for spring outmigrants (5.0%), autumn outmigrants (3.3%) and fish that out‐migrated outside of spring or autumn (2.8%). Spring and autumn outmigrants returned at similar dates (typically mid to late July), but autumn fish were away for longer periods (median = 612 days; spring outmigrants = 104 days). Autumn outmigrants were 25% smaller than spring outmigrants at outmigration and 6% smaller on their return, and within both groups smaller/younger outmigrants spent longer away than larger/older outmigrants. Autumn outmigrants were more likely to return unsilvered as "slob" trout (84%) than spring outmigrants (31%), suggesting they make greater use of brackish habitats that might be safer, but less productive, than fully marine habitats. Nonetheless, both types also produced silvered "sea trout" (≥1+ sea‐age), implying neither is locked into a single life‐history strategy. The findings emphasise that autumn outmigrants and the transitional habitats that support their persistence should not be overlooked in salmonid management and conservation. [ABSTRACT FROM AUTHOR]

Summary: Blumeria graminis f. sp. tritici (Bgt) is a globally important fungal pathogen of wheat that can rapidly evolve to defeat wheat powdery mildew (Pm) resistance genes. Despite periodic regional deployment of the Pm1a resistance gene in US wheat production, Bgt strains that overcome Pm1a have been notably nonpersistent in the United States, while on other continents, they are more widely established.A genome‐wide association study (GWAS) was conducted to map sequence variants associated with Pm1a virulence in 216 Bgt isolates from six countries, including the United States. A virulence variant apparently unique to Bgt isolates from the United States was detected in the previously mapped gene AvrPm1a (BgtE‐5612) on Bgt chromosome 6; an in vitro growth assay suggested no fitness reduction associated with this variant.A gene on Bgt chromosome 8, Bgt‐51526, was shown to function as a second determinant of Pm1a virulence, and despite < 30% amino acid identity, BGT‐51526 and BGTE‐5612 were predicted to share > 85% of their secondary structure. A co‐expression study in Nicotiana benthamiana showed that BGTE‐5612 and BGT‐51526 each produce a PM1A‐dependent hypersensitive response.More than one member of a B. graminis effector family can be recognized by a single wheat immune receptor, and a two‐gene model is necessary to explain virulence to Pm1a. [ABSTRACT FROM AUTHOR]

Objective: Bradykinesia is the major cardinal motor sign of Parkinson disease (PD), but its neural underpinnings are unclear. The goal of this study was to examine whether changes in bradykinesia following long‐term subthalamic nucleus (STN) deep brain stimulation (DBS) are linked to local STN beta (13–30 Hz) dynamics or a wider bilateral network dysfunction. Methods: Twenty‐one individuals with PD implanted with sensing neurostimulators (Activa® PC + S, Medtronic, PLC) in the STN participated in a longitudinal 'washout' therapy study every three to 6 months for an average of 3 years. At each visit, participants were withdrawn from medication (12/24/48 hours) and had DBS turned off (>60 minutes) before completing a repetitive wrist‐flexion extension task, a validated quantitative assessment of bradykinesia, while local field potentials were recorded. Local STN beta dynamics were investigated via beta power and burst duration, while interhemispheric beta synchrony was assessed with STN‐STN beta coherence. Results: Higher interhemispheric STN beta coherence, but not contralateral beta power or burst duration, was significantly associated with worse bradykinesia. Bradykinesia worsened off therapy over time. Interhemispheric STN‐STN beta coherence also increased over time, whereas beta power and burst duration remained stable. The observed change in bradykinesia was related to the change in interhemispheric beta coherence, with greater increases in synchrony associated with further worsening of bradykinesia. Interpretation: Together, these findings implicate interhemispheric beta synchrony as a neural correlate of the progression of bradykinesia following chronic STN DBS. This could imply the existence of a pathological bilateral network contributing to bradykinesia in PD. ANN NEUROL 2023;93:1029–1039 [ABSTRACT FROM AUTHOR]

In this work, the dithiolene complex iron(III) bis‐maleonitriledithiolene [Fe(mnt)2] is characterised and evaluated as a homogeneous CO2 reduction catalyst. Electrochemically the Fe(mnt)2 is reduced twice to the trianionic Fe(mnt)23− state, which is correspondingly found to be active towards CO2. Interestingly, the first reduction event appears to comprise overlapping reversible couples, attributed to the presence of both a dimeric and monomeric form of the dithiolene complex. In acetonitrile Fe(mnt)2 demonstrates a catalytic response to CO2 yielding typical two‐electron reduction products: H2, CO and CHOOH. The product distribution and yield were governed by the proton source. Operating with H2O as the proton source gave only H2 and CO as products, whereas using 2,2,2‐trifluoroethanol gave 38 % CHOOH faradaic efficiency with H2 and CO as minor products. [ABSTRACT FROM AUTHOR]

SARS‐CoV‐2 infection can damage the nervous system with multiple neurological manifestations described. However, there is limited understanding of the mechanisms underlying COVID‐19 neurological injury. This is a cross‐sectional exploratory prospective biomarker cohort study of 21 patients with COVID‐19 neurological syndromes (Guillain–Barre Syndrome [GBS], encephalitis, encephalopathy, acute disseminated encephalomyelitis [ADEM], intracranial hypertension, and central pain syndrome) and 23 healthy COVID‐19 negative controls. We measured cerebrospinal fluid (CSF) and serum biomarkers of amyloid processing, neuronal injury (neurofilament light), astrocyte activation (GFAp), and neuroinflammation (tissue necrosis factor [TNF] ɑ, interleukin [IL]‐6, IL‐1β, IL‐8). Patients with COVID‐19 neurological syndromes had significantly reduced CSF soluble amyloid precursor protein (sAPP)‐ɑ (p = 0.004) and sAPPβ (p = 0.03) as well as amyloid β (Aβ) 40 (p = 5.2 × 10−8), Aβ42 (p = 3.5 × 10−7), and Aβ42/Aβ40 ratio (p = 0.005) compared to controls. Patients with COVID‐19 neurological syndromes showed significantly increased neurofilament light (NfL, p = 0.001) and this negatively correlated with sAPPɑ and sAPPβ. Conversely, GFAp was significantly reduced in COVID‐19 neurological syndromes (p = 0.0001) and this positively correlated with sAPPɑ and sAPPβ. COVID‐19 neurological patients also displayed significantly increased CSF proinflammatory cytokines and these negatively correlated with sAPPɑ and sAPPβ. A sensitivity analysis of COVID‐19‐associated GBS revealed a non‐significant trend toward greater impairment of amyloid processing in COVID‐19 central than peripheral neurological syndromes. This pilot study raises the possibility that patients with COVID‐19‐associated neurological syndromes exhibit impaired amyloid processing. Altered amyloid processing was linked to neuronal injury and neuroinflammation but reduced astrocyte activation. [ABSTRACT FROM AUTHOR]

We performed gene and genome targeted SNP discovery towards the development of a genome‐wide, multispecies genotyping array for tropical pines. Pooled RNA‐seq data from shoots of seedlings from five tropical pine species was used to identify transcript‐based SNPs resulting in 1.3 million candidate Affymetrix SNP probe sets. In addition, we used a custom 40 K probe set to perform capture‐seq in pooled DNA from 81 provenances representing the natural ranges of six tropical pine species in Mexico and Central America resulting in 563 K candidate SNP probe sets. Altogether, 300 K RNA‐seq (72%) and 120 K capture‐seq (28%) derived SNP probe sets were tiled on a 420 K screening array that was used to genotype 576 trees representing the 81 provenances and commercial breeding material. Based on the screening array results, 50 K SNPs were selected for commercial SNP array production including 20 K polymorphic SNPs for P. patula, P. tecunumanii, P. oocarpa and P. caribaea, 15 K for P. greggii and P. maximinoi, 13 K for P. elliottii and 8K for P. pseudostrobus. We included 9.7 K ancestry informative SNPs that will be valuable for species and hybrid discrimination. Of the 50 K SNP markers, 25% are polymorphic in only one species, while 75% are shared by two or more species. The Pitro50K SNP chip will be useful for population genomics and molecular breeding in this group of pine species that, together with their hybrids, represent the majority of fast‐growing tropical and subtropical pine plantations globally. [ABSTRACT FROM AUTHOR]

Objective: To investigate the progression of neural and motor features of Parkinson's disease in a longitudinal study, after washout of medication and bilateral subthalamic nucleus deep brain stimulation (STN DBS). Methods: Participants with clinically established Parkinson's disease underwent bilateral implantation of DBS leads (18 participants, 13 male) within the STN using standard functional frameless stereotactic technique and multi‐pass microelectrode recording. Both DBS leads were connected to an implanted investigative sensing neurostimulator (Activa™ PC + S, Medtronic, PLC). Resting state STN local field potentials (LFPs) were recorded and motor disability, (the Movement Disorder Society‐Unified Parkinson's Disease Rating Scale – motor subscale, MDS‐UPDRS III) was assessed off therapy at initial programming, and after 6 months, 1 year, and yearly out to 5 years of treatment. The primary endpoint was measured at 3 years. At each visit, medication had been held for over 12/24 h and DBS was turned off for at least 60 min, by which time LFP spectra reached a steady state. Results: After 3 years of chronic DBS, there were no increases in STN beta band dynamics (p = 0.98) but there were increases in alpha band dynamics (p = 0.0027, 25 STNs). Similar results were observed in a smaller cohort out to 5 years. There was no increase in the MDS‐UPDRS III score. Interpretation: These findings provide evidence that the beta oscillopathy does not substantially progress following combined STN DBS plus medication in moderate to advanced Parkinson's disease. [ABSTRACT FROM AUTHOR]

Farmers have been interested in using foliar‐applied nutrient products to increase soybean [Glycine max (L.) Merr.] yield since at least the 1970s, despite limited evidence that these products offer consistent yield increases when used prophylactically. Recently, interest in foliar fertilizer products for soybean production has been renewed, likely related to elevated soybean prices. Over the 2019 and 2020 growing seasons (46 site‐years), agronomists in 16 states collaborated to test six foliar nutrient treatments (commercial mixtures of macro‐ and micro‐nutrients) on soybean grain yield and composition. Soybean grain yield and composition differed among sites but not among foliar fertilizer treatments. Results show that prophylactic foliar fertilization is likely to decrease the profitability of soybean production. Foliar fertilizer products tested in this study and similar products should not be recommended to U.S. soybean farmers in the absence of visual symptoms of nutrient deficiency. Core Ideas: The tested prophylactic foliar fertilizers did not increase soybean yield.Foliar fertilizers did not change grain composition.Prophylactic foliar fertilizers tested decreased profitability. [ABSTRACT FROM AUTHOR]

Objectives: In response to a commissioned research update on dementia during the COVID-19 pandemic, a UK-based working group, comprising dementia researchers from a range of fields and disciplines, aimed to describe the impact of the pandemic on dementia wellbeing and identify priorities for future research.Methods: We supplemented a rapid literature search (including unpublished, non-peer reviewed and ongoing studies/reports) on dementia wellbeing in the context of COVID-19 with expert group members' consensus about future research needs. From this we generated potential research questions the group judged to be relevant that were not covered by the existing literature.Results: Themes emerged from 141 studies within the six domains of the NHS England COVID-19 Dementia Wellbeing Pathway: Preventing Well, Diagnosing Well, Treating Well, Supporting Well, Living Well and Dying Well. We describe current research findings and knowledge gaps relating to the impact on people affected by dementia (individuals with a diagnosis, their carers and social contacts, health and social care practitioners and volunteers), services, research activities and organisations. Broad themes included the potential benefits and risks of new models of working including remote healthcare, the need for population-representative longitudinal studies to monitor longer-term impacts, and the importance of reporting dementia-related findings within broader health and care studies.Conclusions: The COVID-19 pandemic has had a disproportionately negative impact on people affected by dementia. Researchers and funding organisations have responded rapidly to try to understand the impacts. Future research should highlight and resolve outstanding questions to develop evidence-based measures to improve the quality of life of people affected by dementia. [ABSTRACT FROM AUTHOR]

Induced pluripotent stem cell (iPSC) technology enables the generation of human neurons in vitro, which contain the precise genome of the cell donor, therefore permitting the generation of disease models from individuals with a disease‐associated genotype of interest. This approach has been extensively used to model inherited forms of Alzheimer's disease and frontotemporal dementia. The combination of iPSC‐derived neuronal models with targeted mass spectrometry analysis has provided unprecedented insights into the regulation of specific proteins in human neuronal physiology and pathology. For example enabling investigations into tau and APP/Aβ, specifically: protein isoform expression, relative levels of cleavage fragments, aggregated species and functionally critical post‐translational modifications. The use of mass spectrometry has enabled a determination of how closely iPSC‐derived models recapitulate disease profiles observed in the human brain. This review will highlight the progress to date in studies using iPSCs and mass spectrometry to model Alzheimer's disease and dementia. We go on to convey our optimism, as studies in the near future will make use of this precedent, together with novel techniques such as genome editing and stable isotope labelling, to provide real progress towards an in depth understanding of early neurodegenerative processes and development of novel therapeutic agents. [ABSTRACT FROM AUTHOR]

Premise: An informatics approach was used for the construction of an Axiom genotyping array from heterogeneous, high‐throughput sequence data to assess the complex genome of loblolly pine (Pinus taeda). Methods: High‐throughput sequence data, sourced from exome capture and whole genome reduced‐representation approaches from 2698 trees across five sequence populations, were analyzed with the improved genome assembly and annotation for the loblolly pine. A variant detection, filtering, and probe design pipeline was developed to detect true variants across and within populations. From 8.27 million variants, a total of 642,275 were evaluated and 423,695 of those were screened across a range‐wide population. Results: The final informatics and screening approach delivered an Axiom array representing 46,439 high‐confidence variants to the forest tree breeding and genetics community. Based on the annotated reference genome, 34% were located in or directly upstream or downstream of genic regions. Discussion: The Pita50K array represents a genome‐wide resource developed from sequence data for an economically important conifer, loblolly pine. It uniquely integrates independent projects that assessed trees sampled across the native range. The challenges associated with the large and repetitive genome are addressed in the development of this resource. [ABSTRACT FROM AUTHOR]

Background: Cerebrospinal fluid (CSF) neurofilament light (NfL) is a dynamic biomarker of neurodegeneration that is used for supporting clinical diagnosis and monitoring disease‐modifying therapies. Development of new analytical tests has been limited, with quantitation of NfL in biomarker studies largely restricted to immunoassay methods. Targeted mass spectrometry is a highly specific technique that can be easily translated into existing proteomic and clinical pathology laboratories. In this multi‐centre study, we have developed two targeted mass spectrometry assays which were compared to Simoa, the gold standard method for NfL quantitation. The developed methods included immunocapture of intact NfL protein or specific peptides (immune‐peptide capture) prior to targeted proteomic analyses. We discuss the development, validation and merits of each technology to quantitate NfL in CSF from healthy controls and several neurodegenerative diseases. Method: CSF was collected from patients with a range of neurological diseases at the National Hospital for Neurology and Neurosurgery (London, UK). Clinical diagnosis was determined by their treating clinician according to consensus clinical criteria. NfL concentrations were measured by Simoa (Quanterix, USA) and two immunoprecipitation‐targeted mass spectrometry (IP‐MS) assays developed by a collaboration between UCL and Washington University in St Louis. To evaluate replication of results across centres and mass spectrometry approaches, results were compared using Spearman's correlation analysis and Bland‐Altman testing. Results: A high correlation was observed for CSF NfL levels between Simoa and both IP‐MS assays (immune‐peptide capture, r = 0.90, P<0.0001 and immune‐protein capture, r = 0.88, P<0.0001). Relative differences in mean NfL concentration between clinical groups remained the same across the analytical methods, with the highest and lowest NfL concentrations observed in the Huntington's disease and the healthy control groups respectively. Interestingly, differences in the extent of correlation between Simoa and IP‐MS were observed between the different clinical groups (r = 0.37 ‐ 0.94). Conclusion: Immunoprecipitation‐targeted mass spectrometry quantitation of NfL correlates highly with NfL Simoa measures across a range of neurodegenerative and neuroinflammatory diseases, and is replicable between laboratories using different immunoprecipitation‐targeted mass spectrometry approaches. [ABSTRACT FROM AUTHOR]

Dinuclear metallodrugs offer much potential in the development of novel anticancer chemotherapeutics as a result of the distinct interactions possible with bio‐macromolecular targets and the unique biological activity that can result. Herein, we describe the development of isostructural homo‐dinuclear OsII–OsII and hetero‐dinuclear OsII–RuII organometallic complexes formed from linking the arene ligands of [M(η6‐arene)(C2O4)(PTA)] units (M=Os/Ru; PTA=1,3,5‐triaza‐7‐phosphaadamantane). Using these complexes together with the known RuII–RuII analogue, a chromatin‐modifying agent, we probed the impact of varying the metal ions on the structure, reactivity and biological activity of these complexes. The complexes were structurally characterised by X‐ray diffraction experiments, their stability and reactivity were examined by using 1H and 31P NMR spectroscopy, and their biological activity was assessed, alongside that of mononuclear analogues, through MTT assays and cell‐cycle analysis (HT‐29 cell line). The results revealed high antiproliferative activity in each case, with cell‐cycle profiles of the dinuclear complexes found to be similar to that for untreated cells, and similar but distinct profiles for the mononuclear complexes. These results indicate these complexes impact on cell viability predominantly through a non‐DNA‐damaging mechanism of action. The new OsII–OsII and OsII–RuII complexes reported here are further examples of a family of compounds operating via mechanisms of action atypical of the majority of metallodrugs, and which have potential as tools in chromatin research. [ABSTRACT FROM AUTHOR]

Understanding the consequences of exotic diseases on native forests is important to evolutionary ecology and conservation biology because exotic pathogens have drastically altered US eastern deciduous forests. Cornus florida L. (flowering dogwood tree) is one such species facing heavy mortality. Characterizing the genetic structure of C. florida populations and identifying the genetic signature of adaptation to dogwood anthracnose (an exotic pathogen responsible for high mortality) remain vital for conservation efforts. By integrating genetic data from genotype by sequencing (GBS) of 289 trees across the host species range and distribution of disease, we evaluated the spatial patterns of genetic variation and population genetic structure of C. florida and compared the pattern to the distribution of dogwood anthracnose. Using genome‐wide association study and gradient forest analysis, we identified genetic loci under selection and associated with ecological and diseased regions. The results revealed signals of weak genetic differentiation of three or more subgroups nested within two clusters—explaining up to 2%–6% of genetic variation. The groups largely corresponded to the regions within and outside the eastern Hot‐Continental ecoregion, which also overlapped with areas within and outside the main distribution of dogwood anthracnose. The fungal sequences contained in the GBS data of sampled trees bolstered visual records of disease at sampled locations and were congruent with the reported range of Discula destructiva, suggesting that fungal sequences within‐host genomic data were informative for detecting or predicting disease. The genetic diversity between populations at diseased vs. disease‐free sites across the range of C. florida showed no significant difference. We identified 72 single‐nucleotide polymorphisms (SNPs) from 68 loci putatively under selection, some of which exhibited abrupt turnover in allele frequencies along the borders of the Hot‐Continental ecoregion and the range of dogwood anthracnose. One such candidate SNP was independently identified in two prior studies as a possible L‐type lectin‐domain containing receptor kinase. Although diseased and disease‐free areas do not significantly differ in genetic diversity, overall there are slight trends to indicate marginally smaller amounts of genetic diversity in disease‐affected areas. Our results were congruent with previous studies that were based on a limited number of genetic markers in revealing high genetic variation and weak population structure in C. florida. [ABSTRACT FROM AUTHOR]

Amelioration of K deficiency during the growing season requires knowledge of critical tissue concentrations and crop yield response to fertilization time. Our objectives were to characterize the yield and uptake responses of K‐deficient irrigated soybean [Glycine max (L.) Merr.] to in‐season fertilizer‐K application time and rate, evaluate fertilizer‐potassium‐recovery efficiency (FKRE), and evaluate how leaflet‐K concentration responds to K‐fertilization time. Six trials were established on silt loam soils. Muriate of potash was applied pre‐plant and compared to an equivalent K rate applied post‐emergence on six or seven dates. Grain yield, trifoliolate‐K concentration, and K uptake were measured. Relative soybean yields were regressed across days after planting (DAP) for two situations of K‐responsive soybean: season‐long K‐deficiency symptoms or few symptoms (hidden hunger). The maximum yield increases from K fertilization ranged from 524 to 1948 kg ha−1 among trials producing relative yields that were 59−90% of the maximum yield produced with the greatest pre‐plant‐applied K rate. A linear‐plateau model showed maximal yields of soybean with hidden hunger could be produced with in‐season fertilizer K applied as late as 83 DAP or 44 d after R1 stage (DAR1). For soybean experiencing season‐long K deficiency, K fertilization from pre‐plant until 60 DAP or about 20 DAR1 produced similar relative yields. The FKRE of pre‐plant‐applied fertilizer K ranged from 36 to 75% among trials. Regardless of the severity of K deficiency, fertilizer K applied post‐emergence into the R2 development stage was taken up efficiently and produced similar yields as equal pre‐plant‐applied K rates. [ABSTRACT FROM AUTHOR]

In this study a bispidine ligand has been applied to the complexation of gallium(III) and radiolabelled with gallium‐68 for the first time. Despite its 5‐coordinate nature, the resulting complex is stable in serum for over two hours, demonstrating a ligand system well matched to the imaging window of gallium‐68 positron emission tomography (PET). To show the versatility of the bispidine ligand and its potential use in PET, the bifunctional chelator was conjugated to a porphyrin, producing a PET/PDT‐theranostic, which showed the same level of stability to serum as the non‐conjugated gallium‐68 complex. The PET/PDT complex killed >90 % of HT‐29 cells upon light irradiation at 50 μm. This study shows bispidines have the versatility to be used as a ligand system for gallium‐68 in PET. [ABSTRACT FROM AUTHOR]

Active targeting strategies are currently being extensively investigated in order to enhance the selectivity of photodynamic therapy. The aim of the present research was to evaluate whether the external decoration of nanopolymeric carriers with targeting peptides could add more value to a photosensitizer formulation and increase antitumor therapeutic efficacy and selectivity. To this end, we assessed PLGA‐PLA‐PEG nanoparticles (NPs) covalently attached to a hydrophilic photosensitizer 5‐[4‐azidophenyl]‐10,15,20‐tri‐(N‐methyl‐4‐pyridinium)porphyrinato zinc (II) trichloride (ZnTriMPyP) and also to c(RGDfK) peptides, in order to target αvβ3 integrin‐expressing cells. In vitro phototoxicity investigations showed that the ZnTriMPyP‐PLGA‐PLA‐PEG‐c(RGDfK) nanosystem is effective at submicromolar concentrations, is devoid of dark toxicity, successfully targets αvβ3 integrin‐expressing cells and is 10‐fold more potent than related nanosystems where the PS is occluded instead of covalently bound. [ABSTRACT FROM AUTHOR]

Applying supplemental fertilizer N or inoculating soybean [Glycine max (L.) Merr.] seed with Bradyrhizobium japonicum led to mixed yield responses. We assessed the profitability of seed inoculation, fertilizing with N, or both, across different planting dates using maturity group (MG) IV and MG V soybean cultivars under irrigated conditions. Planting dates ranged from late May to late June at Fayetteville, AR, and Pine Tree, AR, from 2017 to 2019. Urea fertilizer was applied at R2 at 0 or 56 kg N ha−1 using inoculated soybean. Similarly, non‐inoculated treatments ranged from 0, 28, 56, 112, to 168 kg N ha−1. Although fertilizer did increase yield, the response varied by planting date, was small, and only significant at p = .141 and.171 for linear and non‐linear effects of N, respectively. Seed inoculation had a small negative impact (89 kg ha−1) on yield (p = .0157). Using historical prices over the last 10 yr, optimal fertilizer rates ranged from 3.6 to 6.6 kg N ha−1 with an attendant average yield increase of 32 kg ha−1 for early planting and from 2.6 to 4.1 kg N ha−1 for late planting with an average yield gain of 24 kg ha−1. Regardless of timing of planting, the added yield less attendant fertilizer cost resulted in an average net gain of US$7.39 and $6.00 ha−1, for early and late planting, respectively. That net gain was insufficient to cover additional custom fertilizer application charges of $17.30 ha−1. Hence, inoculation and fertilizer N are not recommended. [ABSTRACT FROM AUTHOR]

Five metal complexes of the dithiolene ligand maleonitriledithiolate (mnt2−) with M=V, Fe, Co, Ni, Cu were studied as redox‐active materials for nonaqueous redox flow batteries (RFBs). All five complexes exhibit at least two redox processes, making them applicable to symmetric RFBs as single‐species electrolytes, that is, as both negolyte and posolyte. Charge–discharge cycling in a small‐scale RFB gave modest performances for [(tea)2Vmnt], [(tea)2Comnt], and [(tea)2Cumnt] whereas [(tea)Femnt] and [(tea)2Nimnt] (tea=tetraethylammonium) failed to hold any significant capacity, indicating poor stability. Independent negolyte‐ and posolyte‐only battery cycling of a single redox couple, as well as UV/Vis spectroscopy, showed that for [(tea)2Vmnt] the negolyte is stable whereas the posolyte is unstable over multiple charge–discharge cycles; for [(tea)2Comnt], [(tea)2Nimnt], and [(tea)2Cumnt], the negolyte suffers rapid capacity fading although the posolyte is more robust. Identifying a means to stabilize Vmnt3−/2− as a negolyte, and Comnt2−/1−, Nimnt2−/1−, and Cumnt2−/1− as posolytes could lead to their use in asymmetric RFBs. [ABSTRACT FROM AUTHOR]

Introduction: Many infectious diseases display seasonal variation corresponding with particular conditions. In orthopaedics a growing body of evidence has identified surges in post‐operative infection rates during higher temperature periods. The aim of this research was to collate and synthesize the current literature on this topic. Methods: A systematic review and meta‐analysis was performed using five databases (PubMed, Embase, CINAHL, Web of Science and Central (Cochrane)). Study quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation method. Odds ratios (ORs) were calculated from monthly infection rates and a pooled OR was generated using the DerSimonian and Lairds method. A protocol for this review was registered with the National Institute for Health Research International Prospective Register of Systematic Reviews (CRD42017081871). Results: Eighteen studies analysing over 19 000 cases of orthopaedic related infection met inclusion criteria. Data on 6620 cases and 9035 controls from 12 studies were included for meta‐analysis. The pooled OR indicated an overall increased odds of post‐operative infection for patients undergoing orthopaedic procedures during warmer periods of the year (pooled OR 1.16, 95% confidence interval 1.04–1.30). Conclusion: A small but significantly increased odds of post‐operative infection may exist for orthopaedic patients who undergo procedures during higher temperature periods. It is hypothesized that this effect is geographically dependent and confounded by meteorological factors, local cultural variables and hospital staffing cycles. [ABSTRACT FROM AUTHOR]

Burgeoning research investigating the effects of daily stress on romantic relationships has paved the way for identifying a variety of means of buffering the negative effects of stress. This article reviews the literature on stress spillover from outside the relationship (extradyadic) on relationship behaviors for both partners to stress inside the relationship, or intradyadic stress, as well as crossover of stress from one partner to another. Analysis of studies on daily stress spillover and crossover in dyads highlights mediators and moderators that can shape future research. Finally, an area central to the life of many people, religious beliefs and behaviors is considered. A meaning‐making process is identified, partner‐focused petitionary prayer, that could buffer the spillover of extradyadic stress on intradyadic stress, as well as the crossover to partner stress, ultimately having an impact on relationship outcomes. The potential to develop interventions around existing daily behaviors is explored. [ABSTRACT FROM AUTHOR]

Soil testing is the best available technology for making crop fertilizer recommendations, and precision agriculture has increased the demand for soil-testing. Our primary research objectives were to validate the accuracy of soil-test P (STP) and K (STK) availability (Mehlich-3) and trifoliolate leaflet-P and leaflet-K concentration interpretations for predicting irrigated-soybean [Glycine max (L.) Merr.] yield response to P and K fertilization at 22 site-years. Each trial contained six treatments involving two P rates and four K rates including a no fertilizer-P or -K control and the soil-test recommendation. Yield and tissue nutrient concentration responses were assessed at three significance levels (p ≤ 0.05, p ≤ 0.10, or p ≤ 0.25) and identified as correct or incorrect according to the response predicted by soil-test recommendations. The accuracy of soil and tissue analyses to predict the correct plant response to fertilization increased as the significance level moved from conservative (p ≤ 0.05) to liberal (p ≤ 0.25). Mehlich-3 STP accurately identified soils that did not respond to fertilizer P and had an overall accuracy of 40 (p ≤ 0.05) to 48% (p ≤ 0.25) in predicting yield response to fertilization. Existing STK interpretations were 72 (p ≤ 0.05) to 82% (p ≤ 0.25) accurate. Critical leaflet-K concentrations accurately identified soybean response to K fertilization at 46 (p ≤ 0.05) to 60% (p ≤ 0.25) of the sites. Interpretation errors were most common in the very low and low STP levels, low and medium STK levels, and the low tissue-K level. The accuracy of the soil and tissue testing and their interpretation process were reasonably accurate for K but substantial improvements are needed for P. [ABSTRACT FROM AUTHOR]

Background: Neurofilament light (NfL) is a neuronal cytoskeletal protein that is released into the extracellular environment from degenerated axons. As such, NfL levels in cerebrospinal fluid (CSF) and serum have been proposed as a promising biomarker of neurodegeneration, yet the metabolism of NfL in human neurons is unknown. Kinetic protein labelling can provide protein half‐lives and rates of production and clearance in vitro and in vivo. Method: Using a stable isotope tracer (13C6‐leucine), we labelled two lines of pluripotent stem cell‐derived neurons and human study participants with primary tauopathies (n = 9). We collected neuronal lysates and conditioned media every three days during the labelling ("pulse") and post‐labelling ("chase") phases. CSF samples were collected across five visits, scheduled around 4, 14, 20, 60 and 120 days post‐labelling. We measured the ratio of labelled to unlabelled NfL using targeted mass spectrometry workflows to quantitate the rates of protein labelling (fractional synthesis rate) and label loss (fractional clearance rate), together providing the protein turnover rate. Result: The average half‐life of NfL in cell lysates was four days (± 1.06 SD, n = 3 independent biological replicates). The turnover of extracellular NfL in neuronal conditioned media was slower than that found in neuronal lysates, suggesting that NfL is a rather stable protein in the extracellular milieu in vitro. In contrast, analysis of CSF from the in vivo tauopathy cohort detected low labelling of NfL (0.04 – 0.36%) by 120 days (n = 5), indicating that in vivo turnover is exceptionally slower than in vitro and that extended CSF collection and analysis >120 days post‐labelling is crucial to capture NfL production and clearance in vivo. To this end, additional analysis of healthy controls and patients with Alzheimer's disease (control and AD cohorts; n = 24), which include CSF collection up to 219 ‐ 444 days post‐labelling, is ongoing. Conclusion: Tracking of both intracellular and extracellular NfL in neurons derived from healthy control individuals, as well as cells with mutations implicated in neurodegenerative diseases, are expected to shed light into the dynamics of NfL turnover in both physiological and pathological conditions. This will be critical for interpreting NfL in response to disease‐modifying therapies. [ABSTRACT FROM AUTHOR]

Background: The choroid plexus secretes protein‐rich cerebrospinal fluid (CSF). CSF turnover is a key mechanism for protein clearance. Neurodegenerative diseases such as AD are characterised by accumulation of excess proteins that form pathological inclusions. CSF flow dysregulation could therefore be involved in the pathophysiology of neurodegenerative diseases (ND) such as Alzheimer's Disease. A method for measuring CSF turnover in vivo may be achieved by quantitating CSF derived protein kinetics, providing a biomarker tool with to interrogate the relationship between CSF flow disequilibrium and neurodegeneration. Method: Using untargeted proteomics we identify the most abundant proteins in a) stem‐cell derived choroid plexus organoids and b) human CSF. We then develop targeted mass spectrometry methods to quantitate protein specific peptides in both matrices. Using a stable isotope (13C6 leucine) we label a) choroid plexus organoids and b) humans with suspected NPH undergoing a 72 hour lumbar drainage protocol. We collect serial samples of the CSF‐like organoid fluid and CSF. We then measure the ratio of labelled to unlabelled peptides to quantitate the rates of protein labelling (fractional synthesis rate) and label loss (fractional clearance rate), defining the protein turnover rate. Result: Highly‐expressed proteins in human CSF from nine individuals were also present in CSF‐like fluid from CP organoids. Of these common proteins, we were able to quantitate the turnover rates of transthyretin, apolipoprotein E, cystatin C and pigment epithelium‐derived factor, and the synthesis rates of serotransferrin and albumin. We will correlate these findings with clinical measures of CSF production. Conclusion: Choroid plexus protein synthesis and clearance can be measured using SILK; choroid plexus organoid fluid protein turnover recapitulates that seen in human CSF. [ABSTRACT FROM AUTHOR]

Background and Aims: Expanded access to naloxone has been identified as a key intervention for reducing opioid‐related morbidity and mortality. It is not known which naloxone device will result in rapid, successful administration when administered by community members. The aims of this study were to estimate and compare (1) the rate of successful administration and (2) time to successful administration for single‐step nasal spray, multi‐step atomized nasal spray and intramuscular simulated naloxone by community members. Design A prospective, single‐site, open‐label, randomized usability assessment of simulated naloxone administration in a convenience sample of community members. Participants were randomized to single‐step nasal spray (SP), multi‐step atomized nasal spray (AT) or intramuscular simulated (IM) naloxone and asked to administer the simulated medication to a mannequin after completing a 2‐minute training video. Setting: New York, USA at a state fair that attracts between 60 000 and 120 000 individuals daily. Participants: A total of 138 participants completed the study over a 2‐day period in September 2016. All participants were at least 18 years of age and had no prior naloxone training. Measurements The rate of successful administration and time to successful administration were recorded for each device. Findings The SP device (100%; P < 0.001) had a higher rate of success compared with the IM device (69.6%). Although success differed between the AT (89.1%) device and IM device, as well as the AT device and SP device, these differences were not significant. The SP device also had a shorter median time to successful administration (34.3 sec) compared with the IM (99.9 sec; P < 0.001) and AT (110.3; P < 0.001) devices. Conclusions: After video training, community members are able to (1) administer single‐step nasal spray naloxone with a higher rate of success than intramuscular naloxone in a simulated overdose setting and (2) administer single‐step nasal spray naloxone more rapidly than both intramuscular and multi‐step atomized nasal spray naloxone. [ABSTRACT FROM AUTHOR]

Trait mindfulness and mindfulness in the context of romantic relationships may not be completely overlapping constructs. This study adapted an existing measure of trait mindfulness to assess the tendency to be mindful in romantic relationships, the Relationship Mindfulness Measure (RMM). Using data from 185 young adults, the results supported the RMM's internal consistency, test-retest reliability, and concurrent and predictive validity. The RMM accounted for a significant portion of variance in positive relationship quality, negative relationship quality, and anxious and avoidant attachment, even after controlling for trait mindfulness. Based on these findings, assessing relationship mindfulness may improve research exploring the role of mindfulness in romantic relations and therefore facilitate the development and refinement of mindfulness training programs for couples. [ABSTRACT FROM AUTHOR]

Abstract: Seventeen cobalt complexes—eleven dinuclear cobalt(II) complexes and three tetranuclear cobalt complexes (two mixed valent) of ditopic ligands, with varying N‐donor aromatic bridging moieties and pendant pyridine side arms, as well as three mononuclear cobalt(II) complexes of Schiff base macrocyclic ligands—have been screened for photocatalytic hydrogen evolution reaction (HER) activity. All 17 complexes are active catalysts for the HER, in both DMF and aqueous solution, in tandem with the [Ru(bpy)3]2+ (bpy=2,2′‐bipyridine) photosensitiser. All are benchmarked to the literature standard [CoIII(dmgH)2(py)Cl] (dmg=dimethylglyoxime, py=pyridine) under identical conditions. Two families of dinuclear cobalt(II) complexes of bis‐tetradentate ligands that provide a triazole bridging moiety and mononuclear cobalt(II) complexes of tetradentate Schiff base macrocycles were found to be the most active catalysts, outperforming [CoIII(dmgH)2(py)Cl] by two‐ to three‐fold. Within these two families, the use of shorter alkyl linkers between the N donors, and hence, smaller chelate ring sizes, was found to significantly enhance catalytic performance, whereas the variation of peripheral functional groups was found to have little effect. This last point will be convenient for subsequent surface immobilisation studies. [ABSTRACT FROM AUTHOR]

Chloride toxicity is a yield limiting problem for soybean [Glycine max (L.) Merr.] production, but limited information is available to accurately diagnose and manage Cl toxicity. The research objective was to determine how incremental additions of Cl affect the yield of Cl excluder and includer cultivars and develop critical leaflet-Cl concentrations that indicate when yield loss from Cl toxicity begins. Six soybean cultivars, three Cl-includer and three Cl-excluder cultivars, were planted at five site-years. Chloride solution containing CaCl2·2H2O and MgCl2·6H2O salts was applied to the soil surface beginning at late vegetative growth with final rates ranging from 0 to 1010 kg Cl ha-1. Tissue Cl concentration was measured by sampling trifoliolate leaflets during reproductive growth. Critical leaflet-Cl concentrations at the R3 stage were developed by regressing relative soybean yield across leaflet-Cl concentration for each cultivar Cl rating. Chloride addition reduced soybean seed yield, on average, by 17% for Cl includer and 5% for excluder cultivars. Leaflet-Cl concentration explained 56% of the variability in relative grain yield for Cl excluders and includers. Relative seed yield declined linearly at 2.6% (1000 mg Cl kg)-1 for cultivars within each Cl rating group with 5% yield loss expected when concentrations exceeded 3923 mg Cl kg-1 for includers and 1885 mg Cl kg-1 for excluders. The ability to predict when potentially toxic amounts of Cl are taken up using tissue analysis is the first step in developing management strategies that may help mitigate yield loss. [ABSTRACT FROM AUTHOR]

Abstract: Alzheimer's disease (AD) is associated with extensive alterations in grey matter microstructure, but our ability to quantify this in vivo is limited. Neurite orientation dispersion and density imaging (NODDI) is a multi‐shell diffusion MRI technique that estimates neuritic microstructure in the form of orientation dispersion and neurite density indices (ODI/NDI). Mean values for cortical thickness, ODI, and NDI were extracted from predefined regions of interest in the cortical grey matter of 38 patients with young onset AD and 22 healthy controls. Five cortical regions associated with early atrophy in AD (entorhinal cortex, inferior temporal gyrus, middle temporal gyrus, fusiform gyrus, and precuneus) and one region relatively spared from atrophy in AD (precentral gyrus) were investigated. ODI, NDI, and cortical thickness values were compared between controls and patients for each region, and their associations with MMSE score were assessed. NDI values of all regions were significantly lower in patients. Cortical thickness measurements were significantly lower in patients in regions associated with early atrophy in AD, but not in the precentral gyrus. Decreased ODI was evident in patients in the inferior and middle temporal gyri, fusiform gyrus, and precuneus. The majority of AD‐related decreases in cortical ODI and NDI persisted following adjustment for cortical thickness, as well as each other. There was evidence in the patient group that cortical NDI was associated with MMSE performance. These data suggest distinct differences in cortical NDI and ODI occur in AD and these metrics provide pathologically relevant information beyond that of cortical thinning. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Deficits in spatial navigation are characteristic and disabling features of typical Alzheimer's disease (tAD) and posterior cortical atrophy (PCA). Visual cues have been proposed to mitigate such deficits; however, there is currently little empirical evidence for their use. Methods: The effect of visual cues on visually guided navigation was assessed within a simplified real‐world setting in individuals with tAD (n = 10), PCA (n = 8), and healthy controls (n = 12). In a repeated‐measures design comprising 36 trials, participants walked to a visible target destination (an open door within a built environment), with or without the presence of an obstacle. Contrast and motion‐based cues were evaluated; both aimed to facilitate performance by applying perceptual changes to target destinations without carrying explicit information. The primary outcome was completion time; secondary outcomes were measures of fixation position and walking path directness during consecutive task phases, determined using mobile eyetracking and motion capture methods. Results: Results illustrate marked deficits in patients’ navigational ability, with patient groups taking an estimated two to three times longer to reach target destinations than controls and exhibiting tortuous walking paths. There were no significant differences between tAD and PCA task performance. Overall, patients took less time to reach target destinations under cue conditions (contrast‐cue: 11.8%; 95% CI: [2.5, 20.3]) and were more likely initially to fixate on targets. Interpretation: The study evaluated navigation to destinations within a real‐world environment. There is evidence that introducing perceptual changes to the environment may improve patients’ navigational ability. [ABSTRACT FROM AUTHOR]

Abstract: Soya bean [Glycine max (L.) Merr] yields >6719 kg/ha (100 bu/ac) have only recently and infrequently been achieved. Quantifying soil property differences between high‐ and average‐yielding areas can help to further identify non‐plant‐related properties contributing to soya bean yield potential. The objective of this study was to evaluate the effects of region and soil depth on soil property differences between high‐ and average‐yielding areas. In each of the seven regions of the ‘Grow for the Green’ yield contest in Arkansas, prior to or just after harvest in 2014 and 2015, soil samples were collected from the top 20 cm of one contest high‐yield (HY) area that was in close proximity to an average‐yield (AY) area. Across all regions and both years, soya bean yields differed (P < 0.05) between yield areas, averaging 4701 and 5498 kg/ha in AY and HY areas, respectively. Averaged across soil depth and years, numerous soil properties differed (P < 0.05) between HY and AY areas within at least one of seven regions. Total soil C content was at least 20.2% greater in the HY than in the AY area in three of seven regions. Extractable soil P content was, on average, 19.4 kg/ha greater in HY than in AY areas in three of the seven regions. Results from this study have the potential to help producers better understand soil properties that contribute to or hinder achieving ultra‐high (>6719 kg/ha) soya bean yields. [ABSTRACT FROM AUTHOR]

Incorporation of {MX}n+ groups into polyoxometalates (POMs) provides the means not only to introduce reactivity and functionality but also to tune the electronic properties of the oxide framework by varying M, X and n. In order to elucidate the factors responsible for differences in reactivity between {TiW5} and {SnW5} Lindqvist-type hexametalates, a series of alkoxido- and aryloxido-tin substituted POMs (nBu4N)3[(RO)SnW5O18] (R=Me, Et, iPr and tBu) and (nBu4N)3[(ArO)SnW5O18] (Ar=C6H5, 4-MeC6H5, 4-tBuC6H5, 4-HOC6H4, 3-HOC6H4 and 2-CHOC6H4) has been structurally characterised and studied by multinuclear NMR (1H, 13C, 17O, 119Sn and 183W) and FTIR spectroscopy. Spectroscopic and structural parameters were compared with those of titanium-substituted homologues and, when coupled with theoretical studies, indicated that Sn−OR and Sn−OAr bonds are ionic with little π-contribution, whereas Ti−OR and Ti−OAr bonds are more covalent with π-bonding that is more prevalent for Ti−OR than Ti−OAr. This experimental and theoretical analysis of bonding in a homologous series of reactive POMs is the most extensive and detailed to date, and reveals factors which account for significant differences in reactivity between tin and titanium congeners. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To assess whether high levels of cerebrospinal fluid neurogranin are found in atypical as well as typical Alzheimer's disease. Methods: Immunoassays were used to measure cerebrospinal fluid neurogranin in 114 participants including healthy controls (n = 27), biomarker‐proven amnestic Alzheimer's disease (n = 68), and the atypical visual variant of Alzheimer's (n = 19) according to international criteria. CSF total‐tau, Aβ42, and neurofilament light concentrations were investigated using commercially available assays. All affected individuals had T1‐weighted volumetric MR images available for analysis of whole and regional brain volumes. Associations between neurogranin, brain volumes, total‐tau, Aβ42, and neurofilament light were assessed. Results: Median cerebrospinal fluid neurogranin concentrations were higher in typical and atypical Alzheimer's compared to controls (P < 0.001 and P = 0.005). Both neurogranin and total‐tau concentrations, but not neurofilament light and Aβ42, were higher in typical Alzheimer's compared to atypical patients (P = 0.004 and P = 0.03). There were significant differences in the left hippocampus and right and left superior parietal lobules in atypical patients, which were larger (P = 0.03) and smaller (P = 0.001 and P < 0.001), respectively, compared to typical patients. We found no evidence of associations between neurogranin and brain volumes but a strong association with total‐tau (P < 0.001) and a weaker association with neurofilament light (P = 0.005). Interpretation: These results show significant differences in neurogranin and total‐tau between typical and atypical patients, which may relate to factors other than disease topography. The differential relationships between neurogranin, total‐tau and neurofilament light in the Alzheimer's variants, provide evidence for mechanistically distinct and coupled markers of neurodegeneration. [ABSTRACT FROM AUTHOR]

This study examines the role of religious coping in couples' diabetes management processes. Eighty-seven couples where one spouse had type 2 diabetes were surveyed. The relationships between religious coping (positive and negative), shared glycemic control activities (e.g., planning a healthy diet), and glycemic control were examined using repeated measures ANOVA and SEM. Findings show spousal engagement in shared activities is significantly associated with glycemic control. Furthermore, the use of negative religious coping by the diabetic spouse, and positive religious coping by the nondiabetic spouse, related to lower levels and higher levels of shared glycemic control activities, respectively. Religious coping and shared glycemic control activities appear integral to couples managing type 2 diabetes and, may serve as useful points of intervention. [ABSTRACT FROM AUTHOR]

Self-assembly of 1:1:2 MII(BF4)2 (M=Zn or Fe), pyrazine-2,5-dicarbaldehyde ( 1) and 2-(2-aminoethyl)pyridine gave trimetallic triangle architectures rather than the anticipated tetrametallic [2×2] squares. Options for the nontrivial synthesis of 1 are considered, and synthetic details provided for both preferred routes. Rare cyclohelicate triangle architectures are observed for the pair of structurally characterized yellow-brown [Zn3 L3](BF4)6 and dark green [Fe3 L3](BF4)6 complexes of the neutral bis-terdentate Schiff base L. In order to form these pyrazine-edged triangles, the octahedral metal ions-with all 6 N-donors provided by the terdentate binding pockets of two L-are located 0.4-0.5 Å out of the plane of the bridging pyrazines, towards the center of the triangle. Density functional theory calculations confirm that simple particle counting entropic arguments, which predict triangles over squares, are correct here, with the triangles shown to be energetically favored over the corresponding squares. However, importantly, DFT analysis of these and related triangle versus square systems also show that vibrational contributions to entropy dominate and may significantly influence the preferred architecture, such that simple particle counting cannot in general be reliably employed to predict the observed architecture. [ABSTRACT FROM AUTHOR]

Objectives Lumbar lordosis (LL) is a key adaptation for bipedalism, but factors underlying curvature variations remain unclear. This study tests three biomechanical models to explain LL variability. Materials and methods Thirty adults (15 male, 15 female) were scanned using magnetic resonance imaging (MRI), a standing posture analysis was conducted, and lumbar range of motion (ROM) was assessed. Three measures of LL were compared. The trunk's center of mass was estimated from external markers to calculate hip moments (Mhip) and lumbar flexion moments. Cross-sectional areas of lumbar vertebral bodies and trunk muscles were measured from scans. Regression models tested associations between LL and the Mhip moment arm, a beam bending model, and an interaction between relative trunk strength (RTS) and ROM. Results Hip moments were not associated with LL. Beam bending was moderately predictive of standing but not supine LL (R2 = 0.25). Stronger backs and increased ROM were associated with greater LL, especially when standing (R2 = 0.65). The strength-flexibility model demonstrates the differential influence of RTS depending on ROM: individuals with high ROM exhibited the most LL variation with RTS, while those with low ROM showed reduced LL regardless of RTS. Discussion Hip moments appear constrained suggesting the possibility of selection, and the beam model explains some LL variability due to variations in trunk geometry. The strength-flexibility interaction best predicted LL, suggesting a tradeoff in which ROM limits the effects of back strength on LL. The strength-flexibility model may have clinical relevance for spinal alignment and pathology. This model may also suggest that straight-backed Neanderthals had reduced lumbar mobility. [ABSTRACT FROM AUTHOR]

A biocompatible fluorescent nanoprobe for singlet oxygen (1O2) detection in biological systems was designed, synthesized, and characterized, that circumvents many of the limitations of the molecular probe Singlet Oxygen Sensor Green® (SOSG). This widely used commercial singlet oxygen probe was covalently linked to a polyacrylamide nanoparticle core using different architectures to optimize the response to 1O2. In contrast to its molecular counterpart, the optimum SOSG-based nanoprobe, which we call NanoSOSG, is readily internalized by E. coli cells and does not interact with bovine serum albumin. Furthermore, the spectral characteristics do not change inside cells, and the probe responds to intracellularly generated 1O2 with an increase in fluorescence. [ABSTRACT FROM AUTHOR]

Forest trees are an unparalleled group of organisms in their combined ecological, economic and societal importance. With widespread distributions, predominantly random mating systems and large population sizes, most tree species harbour extensive genetic variation both within and among populations. At the same time, demographic processes associated with Pleistocene climate oscillations and land-use change have affected contemporary range-wide diversity and may impinge on the potential for future adaptation. Understanding how these adaptive and neutral processes have shaped the genomes of trees species is therefore central to their management and conservation. As for many other taxa, the advent of high-throughput sequencing methods is expected to yield an understanding of the interplay between the genome and environment at a level of detail and depth not possible only a few years ago. An international conference entitled 'Genomics and Forest Tree Genetics' was held in May 2016, in Arcachon (France), and brought together forest geneticists with a wide range of research interests to disseminate recent efforts that leverage contemporary genomic tools to probe the population, quantitative and evolutionary genomics of trees. An important goal of the conference was to discuss how such data can be applied to both genome-enabled breeding and the conservation of forest genetic resources under land use and climate change. Here, we report discoveries presented at the meeting and discuss how the ecological genomic toolkit can be used to address both basic and applied questions in tree biology. [ABSTRACT FROM AUTHOR]

Discovering local adaptation, its genetic underpinnings, and environmental drivers is important for conserving forest species. Ecological genomic approaches coupled with next-generation sequencing are useful means to detect local adaptation and uncover its underlying genetic basis in nonmodel species. We report results from a study on flowering dogwood trees ( Cornus florida L.) using genotyping by sequencing ( GBS). This species is ecologically important to eastern US forests but is severely threatened by fungal diseases. We analyzed subpopulations in divergent ecological habitats within North Carolina to uncover loci under local selection and associated with environmental-functional traits or disease infection. At this scale, we tested the effect of incorporating additional sequencing before scaling for a broader examination of the entire range. To test for biases of GBS, we sequenced two similarly sampled libraries independently from six populations of three ecological habitats. We obtained environmental-functional traits for each subpopulation to identify associations with genotypes via latent factor mixed modeling ( LFMM) and gradient forests analysis. To test whether heterogeneity of abiotic pressures resulted in genetic differentiation indicative of local adaptation, we evaluated Fst per locus while accounting for genetic differentiation between coastal subpopulations and Piedmont-Mountain subpopulations. Of the 54 candidate loci with sufficient evidence of being under selection among both libraries, 28-39 were Arlequin-BayeScan Fst outliers. For LFMM, 45 candidates were associated with climate (of 54), 30 were associated with soil properties, and four were associated with plant health. Reanalysis of combined libraries showed that 42 candidate loci still showed evidence of being under selection. We conclude environment-driven selection on specific loci has resulted in local adaptation in response to potassium deficiencies, temperature, precipitation, and (to a marginal extent) disease. High allele turnover along ecological gradients further supports the adaptive significance of loci speculated to be under selection. [ABSTRACT FROM AUTHOR]

To advance the catalytic applications of s-block mixed-metal complexes, sodium magnesiate [NaMg(CH2SiMe3)3] ( 1) is reported as an efficient precatalyst for the guanylation of a variety of anilines and secondary amines with carbodiimides. First examples of hydrophosphination of carbodiimides by using a Mg catalyst are also described. The catalytic ability of the mixed-metal system is much greater than that of its homometallic components [NaCH2SiMe3] and [Mg(CH2SiMe3)2]. Stoichiometric studies suggest that magnesiate amido and guanidinate complexes are intermediates in these catalytic routes. Reactivity and kinetic studies imply that these guanylation reactions occur via (tris)amide intermediates that react with carbodiiimides in insertion steps. The rate law for the guanylation of N, N′-diisopropylcarbodiimide with 4- tert-butylaniline catalyzed by 1 is first order with respect to [amine], [carbodiimide], and [catalyst], and the reaction shows a large kinetic isotopic effect, which is consistent with an amine-assisted rate-determining carbodiimide insertion transition state. Studies to assess the effect of sodium in these transformations denote a secondary role with little involvement in the catalytic cycle. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) has revolutionized the clinical care of late-stage Parkinson's disease and shows promise for improving the treatment of intractable neuropsychiatric disorders. However, after over 25 years of clinical experience, numerous questions still remain on the neurophysiological basis for the therapeutic mechanisms of action. At their fundamental core, the general purpose of electrical stimulation therapies in the nervous system are to use the applied electric field to manipulate the opening and closing of voltage-gated sodium channels on neurons, generate stimulation induced action potentials, and subsequently, control the release of neurotransmitters in targeted pathways. Historically, DBS mechanisms research has focused on characterizing the effects of stimulation on neurons and the resulting impact on neuronal network activity. However, when electrodes are placed within the central nervous system, glia are also being directly (and indirectly) influenced by the stimulation. Mounting evidence shows that non-neuronal tissue can play an important role in modulating the neurochemistry changes induced by DBS. The goal of this review is to evaluate how DBS effects on both neuronal and non-neuronal tissue can potentially work together to suppress oscillatory activity (and/or information transfer) between brain regions. These resulting effects of ~ 100 Hz electrical stimulation help explain how DBS can disrupt pathological network activity in the brain and generate therapeutic effects in patients. [ABSTRACT FROM AUTHOR]