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CRISPR-associated transposases (CASTs) direct DNA integration downstream of target sites using the RNA-guided DNA binding activity of nuclease-deficient CRISPR-Cas systems. Transposition relies on several key protein-protein and protein-DNA interactions, but little is known about the explicit sequence requirements governing efficient transposon DNA integration activity. Here, we exploit pooled library screening and high-throughput sequencing to reveal novel sequence determinants during transposition by the Type I-F Vibrio cholerae CAST system (VchCAST). On the donor DNA, large transposon end libraries revealed binding site nucleotide preferences for the TnsB transposase, as well as an additional conserved region that encoded a consensus binding site for integration host factor (IHF). Remarkably, we found that VchCAST requires IHF for efficient transposition, thus revealing a novel cellular factor involved in CRISPR-associated transpososome assembly. On the target DNA, we uncovered preferred sequence motifs at the integration site that explained previously observed heterogeneity with single-base pair resolution. Finally, we exploited our library data to design modified transposon variants that enable in-frame protein tagging. Collectively, our results provide new clues about the assembly and architecture of the paired-end complex formed between TnsB and the transposon DNA, and inform the design of custom payload sequences for genome engineering applications with CAST systems.

BACKGROUND: We examined patterns in care for individuals treated for latent TB infection (LTBI) in the US Food and Drug Administration´s Sentinel System.METHODS: Using administrative claims data, we identified patients who filled standard LTBI treatment prescriptions during 2008–2019. In these cohorts, we assessed LTBI testing, clinical management, and treatment duration.RESULTS: Among 113,338 patients who filled LTBI prescriptions, 80% (90,377) received isoniazid (INH) only, 19% (21,235) rifampin (RIF) only, and 2% (1,726) INH + rifapentine (RPT). By regimen, the proportion of patients with documented prior testing for TBI was 79%, 54%, and 91%, respectively. Median therapy duration was 84 days (IQR 35–84) for the 3-month once-weekly INH + RPT regimen, 60 days (IQR 30–100) for the 6- to 9-month INH regimen, and 30 days (IQR 2–60) for the 4-month RIF regimen.CONCLUSIONS: Among the cohorts, INH-only was the most commonly prescribed LTBI treatment. Most persons who filled a prescription for LTBI treatment did not have evidence of completing recommended treatment duration. These data further support preferential use of shorter-course regimens such as INH + RPT.

SummaryThe plant metabolome encompasses the biochemical mechanisms through which evolutionary and ecological processes shape plant form and function1,2. However, while the metabolome should thus be an important component of plant life-history variation3, we know little about how it varies across the plant kingdom. Here, we use the plant functional trait concept4– a powerful framework for describing plant form and function5–7– to interpret leaf metabolome variation among 457 tropical and 339 temperate plant species. Distilling metabolite chemistry into five discriminant metabolic functional traits reveals that plants vary along two major axes of leaf metabolic specialization – a leaf chemical defense spectrum and an expression of leaf longevity. These axes are qualitatively consistent for tropical and temperate species, with many trait combinations being viable. However, axes of leaf metabolic specialization vary orthogonally to life-history strategies described by widely used functional traits5–7, while being at least equally important to them. Our findings question classical trait6and plant defense8theory that predicts relationships between the leaf chemical phenotype, plant productivity, and pace of life. Moreover, we show that metabolic functional traits describe unique dimensions of plant life-history variation that are complementary to, and independent from, those captured by existing plant functional traits.

Membrane separation has enjoyed tremendous advances in relevant material and engineering sciences, making it the fastest growing technology in water treatment. Although membranes as a broad-spectrum physical barrier have great advantages over conventional treatment processes in a myriad of applications, the need for higher selectivity and specificity in membrane separation is rising as we move to target contaminants at trace concentrations and to recover valuable chemicals from wastewater with low energy consumption. In this review, we discuss the drivers, fundamental science, and potential enabling materials for high selectivity membranes, as well as their applications in different water treatment processes. Membrane materials and processes that show promise to achieve high selectivity for water, ions, and small molecules—as well as the mechanisms involved—are highlighted. We further identify practical needs, knowledge gaps, and technological barriers in both material development and process design for high selectivity membrane processes. Finally, we discuss research priorities in the context of existing and future water supply paradigms.

SummaryPlants display an incredible variety of forms and functions, which sustains a vast diversity of ecosystems on Earth. This diversity is the result of two forces: environmental filtering, the selection of phenotypes fit to a specific habitat; and evolutionary history, genetic constraints that determine the potential adaptations that species may evolve. To date, most studies have focused on describing macroecological patterns of trait variation, while the role of evolutionary history in determining these patterns has remained much less explored. Here, we combine a traits dataset including 4,213 vascular plant species with a phylogeny of the plant kingdom, to determine the influence of evolutionary history on the patterns of trait variation. Our results show that commonly used plant traits, such as plant height or leaf nitrogen, are strongly constrained by evolutionary history. Accounting for phylogenetic relationships changes the variance explained by the main axes of trait variation in the Plant Kindgom —the leaf economic spectrum and the plant size and organ axis continuum— with the former explaining more variance than the latter. Moreover, we demonstrate that the plant size continuum is more influenced by evolutionary history than the leaf economics spectrum. These results highlight the influence of evolutionary history in shaping plant life history strategies and the importance of accounting for phylogeny in trait-based studies.

As privileged structures, natural products often display potent biological activities. However, the discovery of novel bioactive scaffolds is often hampered by the chemical complexity of the biological matrices they are found in. Large natural extract collections are thus extremely valuable for their chemical novelty potential but also complicated to exploit in the frame of drug-discovery projects. In the end, it is the pure chemical substances that are desired for structural determination purposes and bioactivity evaluation. Researchers interested in the exploration of large and chemodiverse extract collections should thus establish strategies aiming to efficiently tackle such chemical complexity and access these structures. Establishing carefully crafted digital layers documenting the spectral and chemical complexity as well as bioactivity results of natural extracts collections can help prioritize time-consuming but mandatory isolation efforts. In this note, we report the results of our initial exploration of a collection of 1,600 plant extracts in the frame of a drug-discovery effort. After describing the taxonomic coverage of this collection, we present the results of its liquid chromatography high-resolution mass spectrometric profiling and the exploitation of these profiles using computational solutions. The resulting annotated mass spectral dataset and associated chemical and taxonomic metadata are made available to the community, and data reuse cases are proposed. We are currently continuing our exploration of this plant extract collection for drug-discovery purposes (notably looking for novel antitrypanosomatids, anti-infective and prometabolic compounds) and ecometabolomics insights. We believe that such a dataset can be exploited and reused by researchers interested in computational natural products exploration.

Introduction: Tessier 30 facial cleft is a rare anomaly presenting in the soft and hard tissues over the central lower face. Owing to the rarity of cases and difficulty of treatment, there is no universally accepted surgical management strategy. The last comprehensive literature review of Tessier 30 clefts was in 1996. This report aims to update the literature to inform decision-making on treating Tessier 30 cases. Methodology: A literature search was performed. PubMed, SCOPUS, and OVID databases were searched. A total of 72 cases in 51 articles were analyzed, looking at demographics, extent of cleft, parent health, family history, procedures, follow-up, existence of other anomalies, and stages of repair. Results: Surgeons are increasingly choosing to repair Tessier 30 defects in one rather than multiple stages. Of the 72 cases studied, only 31 had documented the completed repair of the cleft. All completed soft tissue only defects were repaired in 1 stage of repair (n = 11). Where both soft tissue and mandible was involved (n = 20), 55% (n = 11) had undergone 1-stage repair to address the Tessier 30 cleft. Discussion: We argue that a single-stage approach is preferable to multistage. Primary mucogingivoperiosteoplasty should be undertaken in children at the time of management of the soft tissue cleft. The timing of this procedure should be in the latter half of the first year of life, as this is when mandibular symphyseal fusion normally occurs. We have suggested a treatment protocol and we hope that future case reports use our minimum data set.

Septic leach field design in the arid southwestern US requires direct testing of soils to ensure adequate drainage. We propose that direct testing costs can be reduced if electrical geophysical methods are used to determine soil structure that facilitates proper drainage rates. We demonstrate this concept at a residential site where resistivity and induced polarization data were acquired within a desert soil with variable mixtures of clay (Argid) and calcareous (Orthid) components. Electrode arrays were tested to ensure high data quality and minimal workload during inversion modeling. The resulting resistivity structure identified a sharp boundary between the eastern and western halves of the property. The west was more conductive than the east, which could indicate the presence of higher moisture or higher clay content. Chargeability data gathered from the induced polarization survey showed similar stark patterns between east and west halves of the property. The western portion of the survey area was verified to have some clay based on high chargeability values and direct soil testing from pits. Test pits dug to 3.65 m showed transitions between Argid and Othid conditions; the test pits were in locations of moderate resistivity and low chargeability. From this study, we concluded that resistivity and IP were useful in septic design because they reduce the total amount of direct testing needed when testing locations are carefully chosen based on the geophysical results.

PurposeThe aim of this study was to re-evaluate the differentiation of patients with dementia with Lewy bodies (DLB) from Alzheimer’s disease (AD) and Parkinson’s disease (PD) using a quantitative analysis of 123I-FP-CIT SPECT scans.MethodsThirty-six patients with in vivo 123I-FP-CIT SPECT and neuropathological diagnoses were included. Based on neuropathological criteria, patients were further subclassified into nine AD, eight DLB, ten PD and nine with other diagnoses. An additional 16 healthy controls (HC) scanned with 123I-FP-CIT SPECT were also included. All images were visually assessed as normal versus abnormal uptake by consensus of five nuclear medicine physicians. Bihemispheric mean was calculated for caudate binding potential (CBP), putamen binding potential (PBP) and putamen-to-caudate ratio (PCR).ResultsPatients with DLB had significantly lower CBP and PBP than patients with AD and significantly higher PCR than patients with PD. Qualitative visual analysis of the images gave an accuracy of 88% in the evaluation of the status of the nigrostriatal pathway considering all individuals, and 96% considering only the patients with PD, AD and DLB. Quantitative analyses provided a balanced accuracy of 94%, 94% and 100% in binary classifications DLB versus AD, DLB versus PD and PD versus AD, respectively, and an accuracy of 93% in the differentiation among patients with DLB, AD and PD simultaneously. No statistically significant differences were observed between the AD and HC.ConclusionsThis study demonstrates a very high diagnostic accuracy of the quantitative analysis of(123I-FP-CIT SPECT data to differentiate among patients with DLB, PD and AD.

Water matrix composition impacts water treatment performance. However, matrix composition impacts have rarely been studied for electrochemical water treatment processes, and the correlation between the composition and the treatment efficiency is lacking. This work evaluated the electrochemical reduction of nitrate (ERN) using different complex water matrices: groundwater, brackish water, and reverse osmosis (RO) concentrate/brine. The ERN was conducted using a tin (Sn) cathode because of the high selectivity towards nitrogen evolution reported for Sn electrocatalysts. The co-existence of calcium (Ca

The transcription factor heat shock factor-1 (HSF-1) regulates the heat shock response (HSR), a cytoprotective response induced by proteotoxic stresses. Data from model organisms has shown that HSF-1 also has non-stress biological roles, including roles in the regulation of development and longevity. To better study HSF-1 function, we created a C. elegans strain containing HSF-1 tagged with GFP at its endogenous locus utilizing CRISPR/Cas9-guided transgenesis. We show that the HSF-1::GFP CRISPR worm strain behaves similarly to wildtype worms in response to heat and other stresses, and in other physiological processes. HSF-1 was expressed in all tissues assayed. Immediately following the initiation of reproduction, HSF-1 formed nuclear stress bodies, a hallmark of activation, throughout the germline. Upon the transition to adulthood, of HSF-1 nuclear stress bodies appeared in most somatic cells. Genetic loss of the germline suppressed nuclear stress body formation with age, suggesting that the germline influences HSF-1 activity. Interestingly, we found that various neurons did not form nuclear stress bodies after transitioning to adulthood. Therefore, the formation of HSF-1 nuclear stress bodies upon the transition to adulthood does not occur in a synchronous manner in all cell types. In sum, these studies enhance our knowledge of the expression and activity of the aging and proteostasis factor HSF-1 in a tissue-specific manner with age. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12192-020-01188-9.

Post-treatment of brine produced by reverse osmosis (RO) is a great challenge as it often requires high energy input and works under extreme operating conditions. In this study, brine from a RO plant in El Paso, TX USA was successfully treated using a pilot-scale nanophotonics enhanced solar membrane distillation (NESMD) system. The novel NESMD reactor has a nanophotonic membrane surface area of 0.2 m2 and an internal heat recovery system to recover the latent heat released during vapor condensation. By utilizing a sweeping gas operational mode under real solar irradiation (585–827 W m−2), the NESMD realized successful desalination of RO brine with the membrane flux reaching 0.45–0.65 kg m−2 h−1 and total dissolved solids (TDS) removal greater than 99.5% without an external heat condenser. The decrease in the feed flow rate to the evaporation channel of the NESMD system led to an increase in the gained output ratio (GOR) from 0.35 to 0.62. To the best of our knowledge, this is the largest photothermal reactor utilized for the desalination of real RO brine under practical solar irradiation. Compared with conventional brine treatment processes that require high temperature or pressure, the NESMD desalinates RO brine at near-ambient temperature and pressure with free solar energy, providing a promising approach for water desalination, and RO brine post treatment.

The strongest storm in Philippines history, super-typhoon Haiyan, barreled through central Philippines in 2013 and left a high death toll and extensive destruction in its wake. Past studies have investigated Fading Affect Bias (FAB) in extremely negative situations like the death of a loved one and found that the FAB generally occurs in those extreme situations, but this study is the first to assess FAB in first-hand memories for a natural disaster survival situation. The FAB phenomenon is the tendency for emotional intensity associated with negative memories for events to fade over time and emotional intensity for positive events stays relatively stable over time. Researchers collected memories for the super-typhoon from survivors three years after the event. Results showed that negative emotional intensity for the event faded after the event. Emotion in comparison positive memories for non-typhoon events did not fade, and emotion in comparison negative memories faded, following results in several other FAB studies. The Positive and Negative Affect Scale (PANAS) was used as an initial assessment of mood before the study began, and PANAS scores reliably predicted current emotional intensity scores. Memory vividness and emotional intensity in first-hand accounts of a natural disaster experience behave like vividness and intensity in flashbulb memories, but details in first-hand accounts are similar to the amount of details in memories of near-death experiences. How memory rehearsal behaves in relation to time elapsed since event has yet to be captured for first-hand survival experiences.

The aims of this study were to find out whether scoring in a rose-trellis pattern improved the stretch of mucoperiosteal flaps more than conventional scoring in the horizontal plane, and to consider its application in the closure of oroantral communications. Sixteen sections of cadaveric porcine buccal mucoperiosteum were removed from the molar region of the maxilla and mandible. A three-sided flap was raised in the subperiosteal plane, excised, and pinned to a cork board with the periosteal side facing upwards. Eight samples were scored in the horizontal plane (control) using lines perpendicular to the line of simulated advancement, and eight in a rose-trellis or criss-cross pattern. Scoring using a rose-trellis pattern yielded a mean increase in stretch of 24.3% (p = 0.0003) when compared with the conventional method. Buccal advancement flaps are widely used to close oroantral communications, and scoring of the mucoperiosteum facilitates the stretching of the tissue over the defect. To be successful, defects should be fully closed to prevent contamination, and closure should be tension-free. In this study, scoring in a rose-trellis pattern increased the stretch of the tissue sample more than scoring in the horizontal plane. The rose-trellis technique therefore could aid the effective closure of oroantral communications.

Electro-driven technologies are viewed as a potential alternative to the current state-of-the-art technology, reverse osmosis, for the desalination of brackish waters. Capacitive deionization (CDI), based on the principle of electrosorption, has been intensively researched under the premise of being energy efficient. However, electrodialysis (ED), despite being a more mature electro-driven technology, has yet to be extensively compared to CDI in terms of energetic performance. In this study, we utilize Nernst-Planck based models for continuous flow ED and constant-current membrane capacitive deionization (MCDI) to systematically evaluate the energy consumption of the two processes. By ensuring equivalently sized ED and MCDI systems-in addition to using the same feed salinity, salt removal, water recovery, and productivity across the two technologies-energy consumption is appropriately compared. We find that ED consumes less energy (has higher energy efficiency) than MCDI for all investigated conditions. Notably, our results indicate that the performance gap between ED and MCDI is substantial for typical brackish water desalination conditions (e.g., 3 g L-1 feed salinity, 0.5 g L-1 product water, 80% water recovery, and 15 L m-2 h-1 productivity), with the energy efficiency of ED often exceeding 30% and being nearly an order of magnitude greater than MCDI. We provide further insights into the inherent limitations of each technology by comparing their respective components of energy consumption, and explain why MCDI is unable to attain the performance of ED, even with ideal and optimized operation.

Climate warming is releasing carbon from soils around the world, constituting a positive climate feedback. Warming is also causing species to expand their ranges into new ecosystems. Yet, in most ecosystems, whether range expanding species will amplify or buffer expected soil carbon loss is unknown. Here, we used two whole-community transplant experiments and a follow-up glasshouse experiment to determine whether the establishment of herbaceous lowland plants in alpine ecosystems influences soil carbon content under warming. We found that warming (transplantation to low elevation) led to a negligible decrease in alpine soil carbon content, but its effects became significant and 52% ± 31% (mean ± 95% confidence intervals) larger after lowland plants were introduced at low density into the ecosystem. We present evidence that decreases in soil carbon content likely occurred via lowland plants increasing rates of root exudation, soil microbial respiration, and CO2 release under warming. Our findings suggest that warming-induced range expansions of herbaceous plants have the potential to alter climate feedbacks from this system, and that plant range expansions among herbaceous communities may be an overlooked mediator of warming effects on carbon dynamics., eLife, 11, ISSN:2050-084X

1. A major aim of ecology is to upscale attributes of individuals to understand processes at population, community and ecosystem scales. Such attributes are typically described using functional traits, that is, standardised characteristics that impact fitness via effects on survival, growth and/or reproduction. However, commonly used functional traits (e.g. wood density, SLA) are becoming increasingly criticized for not being truly mechanistic and for being questionable predictors of ecological processes. 2. This Special Feature reviews and studies how the metabolome (i.e. the thousands of unique metabolites that underpin physiology) can enhance trait-based ecology and our understanding of plant and ecosystem functioning. 3. In this Editorial, we explore how the metabolome relates to plant functional traits, with reference to life-history trade-offs governing fitness between generations and plasticity shaping fitness within generations. We also identify solutions to challenges of acquiring, interpreting and contextualising metabolome data, and propose a roadmap for integrating the metabolome into ecology. 4. We next summarise the seven studies composing the Special Feature, which use the metabolome to examine mechanisms behind plant community assembly, plant-organismal interactions and effects of plants and soil micro-organisms on ecosystem processes. 5. Synthesis. We demonstrate the potential of the metabolome to improve mechanistic and predictive power in ecology by providing a high-resolution coupling between physiology and fitness. However, applying metabolomics to ecological questions is currently limited by a lack of conceptual, technical and data frameworks, which needs to be overcome to realise the full potential of the metabolome for ecology. ISSN:0022-0477

Food allergies and other immune-mediated diseases have become serious health concerns amongst infants and children in developed and developing countries. The absence of available cures limits disease management to allergen avoidance and symptomatic treatments. Research has suggested that the presence of maternal food allergies may expose the offspring to genetic predisposition, making them more susceptible to allergen sensitization. The following review has focused on epidemiologic studies regarding maternal influences of proneness to develop food allergy in offspring. The search strategy was “food allergy OR maternal effects OR offspring OR prevention”. A systematically search from PubMed/MEDLINE, Science Direct and Google Scholar was conducted. Specifically, it discussed the effects of maternal immunity, microbiota, breastfeeding, genotype and allergy exposure on the development of food allergy in offspring. In addition, several commonly utilized prenatal and postpartum strategies to reduce food allergy proneness were presented, including early diagnosis of high-risk infants and various dietary interventions.

The functional adaptive responses of higher plants to biotic interactions with herbivores and fungi have long been topics of research. One constraint to obtaining a comprehensive understanding of the most general plant responses, however, has been the difficulty of studying all plant functional shifts simultaneously due to analytical limitations. Now this is possible with the advent of metabolomics. Using 151 records from the WEB of SCIENCE database, we have analyzed the development and application of metabolomic profiles to ecological studies in the last two decades. We have used meta-analysis and pathway enrichment analyses to assess the whole set of constitutive and inducible defenses. Constitutive defenses against herbivores were mainly based on a significant high level of the metabolism of several amino acids with parallel increases in the concentrations of flavones (phenolics) and saponins (glycosides). Inducible defenses, though, were mainly based on the increases in concentration of methyl-ketone, pantothenate, and Coenzyme A. Butyrate metabolism and the mitochondrial electron-transport chain were upregulated, in agreement with previous reports that herbivory-activated plant chemical defenses were mainly based on jasmonic acid, salicylic acid, and ethylene-associated pathways. The metabolic responses/acclimations to pathogenic fungi were mainly linked with increases in aspartate and pyruvate metabolism, the transfer of acetyl groups within mitochondria, and the upregulation of branched-chain amino acids degradation pathways. These responses/acclimations were accompanied by higher concentrations of the most important groups of secondary metabolites such as phenolics (anthocyanins, flavonoids), quinones, alkaloids, terpenoids, and polyamines and other compounds related to antistress mechanisms such as proline. The leaves of mycorrhized plants accumulated nucleotide sugars, sphingolipids, and methylhistidine. These responses were associated with maintaining the integrity of plant cell membranes under fungal hypha penetration. The responses were accompanied by increases in the concentrations of phenolics, blumenols, and alkaloids and decreases in the concentrations of polyamines, consistent with the mycorrhizal inhibition of polyamines. This summary provides a clear synthesis of the most successful plant strategies selected after millions of years of evolution and will be a very promising tool for the management of crops and ecosystems and for selecting the main lines in breeding studies for future research., Ecosphere, 12 (9), ISSN:2150-8925

Per- and polyfluoroalkyl substances (PFAS), which are present in many waters, have detrimental impacts on human health and the environment. Reverse osmosis (RO) and nanofiltration (NF) have shown excellent PFAS separation performance in water treatment; however, these membrane systems do not destroy PFAS but produce concentrated residual streams that need to be managed. Complete destruction of PFAS in RO and NF concentrate streams is ideal, but long-term sequestration strategies are also employed. Because no single technology is adequate for all situations, a range of processes are reviewed here that hold promise as components of treatment schemes for PFAS-laden membrane system concentrates. Attention is also given to relevant concentration processes because it is beneficial to reduce concentrate volume prior to PFAS destruction or sequestration. Given the costs and challenges of managing PFAS in membrane concentrates, it is critical to evaluate both established and emerging technologies in selecting processes for immediate use and continued research.