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In plant biology research, X-ray computed tomography (CT) has been demonstrated to be useful for studying the complex tissues of trees qualitatively and quantitatively. The cambium plays a very important role in plant growth and development. However, this tissue is relatively poorly studied due to its complex nature and its localization between layers of xylem and phloem cells. Antecedent environmental conditions may have a substantial impact on plant responses to drought and recovery dynamics. Therefore, this study aimed to investigate the impact of previous drought exposure on the 3D microstructure of two commercial Eucalyptus clones by monitoring the development of the cambium, in the same plant and same area of cambial tissue, during a 4-week trial consisting of well-watered, mild drought, severe drought, and rewatering phases. To track microstructural changes, the plants were imaged weekly with non-destructive X-ray micro-computed tomography (μCT). On the last day of the experiment, X-ray nano-CT was also performed. Our results indicate that trees subjected to earlier well-watered conditions were more affected by the severe drought, compared to those previously exposed to mild drought conditions. Thus, previous exposure to water deficit may provide the benefit of increased drought tolerance during future water deficit. Previous mild drought exposure can facilitate morphological adjustments, which potentially enhances drought tolerance during subsequent drought events. [ABSTRACT FROM AUTHOR]

Though artificial intelligence (AI) is being widely implemented in gastroenterology (GI) and hepatology and has the potential to be paradigm shifting for clinical practice, its pitfalls must be considered along with its advantages. Currently, although the use of AI is limited in practice to supporting clinical judgment, medicine is rapidly heading toward a global environment where AI will be increasingly autonomous. Broader implementation of AI will require careful ethical considerations, specifically related to bias, privacy, and consent. Widespread use of AI raises concerns related to increasing rates of systematic errors, potentially due to bias introduced in training datasets. We propose that a central repository for collection and analysis for training and validation datasets is essential to overcoming potential biases. Since AI does not have built-in concepts of bias and equality, humans involved in AI development and implementation must ensure its ethical use and development. Moreover, ethical concerns regarding data ownership and health information privacy are likely to emerge, obviating traditional methods of obtaining patient consent that cover all possible uses of patient data. The question of liability in case of adverse events related to use of AI in GI must be addressed among the physician, the healthcare institution, and the AI developer. Though the future of AI in GI is very promising, herein we review the ethical considerations in need of additional guidance informed by community experience and collective expertise. [ABSTRACT FROM AUTHOR]

Future climatic scenarios forecast increasingly frequent droughts that will pose substantial consequences on tree mortality. In light of this, drought-tolerant eucalypts have been propagated; however, the severity of these conditions will invoke adaptive responses, impacting the commercially valuable wood properties. To determine what mechanisms govern the wood anatomical adaptive response, highly controlled drought experiments were conducted in Eucalyptus grandis W. Hill ex Maiden, with the tree physiology and transcriptome closely monitored. In response to water deficit, E. grandis displays an isohydric stomatal response to conserve water and enable stem growth to continue, albeit at a reduced rate. Maintaining gaseous exchange is likely a critical short-term response that drives the formation of hydraulically safer xylem. For instance, the development of significantly smaller fibers and vessels was found to increase cellular density, thereby promoting drought tolerance through improved functional redundancy, as well as implosion and cavitation resistance. The transcriptome was explored to identify the molecular mechanisms responsible for controlling xylem cell size during prolonged water deficit. Downregulation of genes associated with cell wall remodeling and the biosynthesis of cellulose, hemicellulose and pectin appeared to coincide with a reduction in cellular enlargement during drought. Furthermore, transcript levels of NAC and MYB transcription factors, vital for cell wall component biosynthesis, were reduced, while those linked to lignification increased. The upregulation of EgCAD and various peroxidases under water deficit did not correlate with an increased lignin composition. However, with the elevated cellular density, a higher lignin content per xylem cross-sectional area was observed, potentially enhancing hydraulic safety. These results support the requirement for higher density, drought-adapted wood as a long-term adaptive response in E. grandis , which is largely influenced by the isohydric stomatal response coupled with cellular expansion-related molecular processes. [ABSTRACT FROM AUTHOR]

Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on colorectal cancer (CRC) risk. We leveraged pooled data from 52 clinical trial, cohort, and case-control studies that included 30,806 CRC cases and 41,861 controls of European ancestry to conduct a genome-wide interaction scan between regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and imputed genetic variants. After adjusting for multiple comparisons, we identified statistically significant interactions between regular aspirin/NSAID use and variants in 6q24.1 (top hit rs72833769), which has evidence of influencing expression of TBC1D7 (a subunit of the TSC1-TSC2 complex, a key regulator of MTOR activity), and variants in 5p13.1 (top hit rs350047), which is associated with expression of PTGER4 (codes a cell surface receptor directly involved in the mode of action of aspirin). Genetic variants with functional impact may modulate the chemopreventive effect of regular aspirin use, and our study identifies putative previously unidentified targets for additional mechanistic interrogation. [ABSTRACT FROM AUTHOR]

Data science can contribute valuable predictions in diverse fields. But I write to express some concerns and red flags. I suggest that data science is being oversold. This article contains three questions that I believe data science must address as this new discipline matures. Is data science significantly different from statistics? This is a question that has haunted the field since the term first was introduced. By creating algorithms based on current societal decision rules that may be biased, even bigoted, does data science lock in and exacerbate inequality? Scholars have identified a continuum from data to information to knowledge to wisdom, with the ultimate goal being wisdom. Data scientists seem to be acting as though data alone are enough. The big data systems are mathematically complex and have predictive power, but can data science contribute significantly to our body of knowledge? [ABSTRACT FROM AUTHOR]

Summary: In recent years, the popularity of X-ray computed tomography (CT), as a non-destructive imaging technique, has continued to expand in various research domains. In wood research, X-ray CT has proven to be useful for three-dimensional (3D) structural studies investigating the complex tissues of trees. Wood formation (i.e., xylogenesis) initiates in the cambium and a narrow zone of subsequent differentiation, both of which play key roles in plant growth and development. However, the dynamics of xylogenesis in eucalypts remain relatively poorly understood, in large part due to challenges in sampling, imaging, and characterizing the cambium. Therefore, the aim of this study was to present a workflow to evaluate the feasibility of using X-ray CT to characterize and quantify the structural properties of the cambium in eucalypts. The growth responses of Corymbia hybrid seedlings, exposed to either irrigated or droughted conditions, was investigated by monitoring the structural development of the cambium. To track microstructural changes in the cambium, the same seedlings were imaged with X-ray micro-CT (μ CT) one day before the treatments and again six days after the respective treatments. After the last X-ray μ CT scan, X-ray nano-CT was also applied. Using image analysis techniques, the morphological characteristics of the cambium could be determined. X-ray μ CT displayed a larger, thicker cambial zone in irrigated plants, while a much thinner cambium was visible in droughted seedlings. X-ray nano-CT revealed that droughted plants were associated with a significantly (p ⩽ 0.05) smaller cambium volume containing smaller cells, compared to the cambium of irrigated plants. Light microscopy was used to validate the CT results and demonstrated no significant (p > 0.05) difference in the cambium width and cell diameter obtained from the two respective CT techniques. The findings of this study proved X-ray CT to be a valuable tool for examining the effect of changing environmental conditions on the complex cambium structure of Corymbia hybrid seedlings. [ABSTRACT FROM AUTHOR]

This study explored if and how principal practices from diverse leadership models could be integrated to predict burned out, ineffective, overextended, or engaged teachers. This unique approach produced an actionable blend of practices and the frequency explaining teacher outcomes. A sample of 240 teachers rated frequency of 58 principal principal practices via an online survey. Discriminant function analysis produced two integrated functions which improved prediction of teacher outcomes. The optimal frequency was "sometimes." Function two, "community learning," had optimal impact on teachers when engaged "frequently." Both functions were needed to predict "engaged" teachers. [ABSTRACT FROM AUTHOR]

The frequency and severity of drought events are expected to increase due to climate change, with optimal environmental conditions for forestry likely to shift. Modeling plant responses to a changing climate is therefore vital. We tested the process-based gain–risk model to predict stomatal responses to drought of two Eucalyptus hybrids. The process-based gain-risk model has the advantage that all the parameters used within the model are based on measurable plant traits. The gain-risk model proposes that plants optimize photosynthetic gain while minimizing a hydraulic cost. Previous versions of the model used hydraulic risk as a cost function; however, they did not account for delayed or reduced hydraulic recovery rates from embolism post-drought. Hydraulic recovery has been seen in many species, however it is still unclear how this inclusion of a partial or delayed hydraulic recovery would affect the predictive power of the gain-risk model. Many hydraulic parameters required by the model are also difficult to measure and are not freely available. We therefore tested a simplified gain-risk model that includes a delayed or reduced hydraulic recovery component post-drought. The simplified gain-risk model performed well at predicting stomatal responses in both Eucalyptus grandis × camaldulensis (GC) and Eucalyptus urophylla × grandis (UG). In this study two distinct strategies were seen between GC and UG , with GC being more resistant to embolism formation, however it could not recover hydraulic conductance compared with UG. The inclusion of a delayed or reduced hydraulic recovery component slightly improved model predictions for GC , however not for UG , which can be related to UG being able to recover lost hydraulic conductance and therefore can maintain stomatal conductance regardless of hydraulic risk. Even though the gain-risk model shows promise in predicting plant responses, more information is needed regarding hydraulic recovery after drought. [ABSTRACT FROM AUTHOR]

Lately, much has been written about the importance of amplifying statistics related content in the K-12 curricula. This can be viewed in parallel or as an addendum to the existing mathematics curricula in the United States. Nevertheless, a key component of this debate is the lack of robust and cutting-edge academic programs in statistics education. In this piece, we emphasize the urgent need for investing in creating strong statistics education programs, which would significantly contribute to nurturing quantitative literacy as well as preparing a more informed citizenry in the 21st century. [ABSTRACT FROM AUTHOR]

This study explored whether license-holding mental health professionals exhibit comfort/discomfort in addressing religion and spirituality (RS) in practice. Through snowball sampling, 52 clinicians across different fields were recruited across Southern California. The participants were measured descriptively based on (a) comfort in their ability to integrate clients' RS in treatment and (b) their comfort discussing clients' RS strengths and struggles in treatment. Results revealed that, among practitioners, there was a 15–25% level of discomfort toward integrating and discussing RS in treatment. That is, between 75% and 85% of participants reported comfort in dealing with RS in practice. Licensed clinical social workers reported slightly lower discomfort level than other licensed professionals. However, Mann-Whitney U Test results revealed that field of practice (social workers versus non social workers) does not significantly correlate with comfort addressing and discussing RS in treatment. Implications of the findings were discussed. [ABSTRACT FROM AUTHOR]

The major facilitator superfamily (MFS) is the largest known superfamily of secondary active transporters. MFS transporters are responsible for transporting a broad spectrum of substrates, either down their concentration gradient or uphill using the energy stored in the electrochemical gradients. Over the last 10 years, more than a hundred different MFS transporter structures covering close to 40 members have provided an atomic framework for piecing together the molecular basis of their transport cycles. Here, we summarize the remarkable promiscuity of MFS members in terms of substrate recognition and proton coupling as well as the intricate gating mechanisms undergone in achieving substrate translocation. We outline studies that show how residues far from the substrate binding site can be just as important for fine-tuning substrate recognition and specificity as those residues directly coordinating the substrate, and how a number of MFS transporters have evolved to form unique complexes with chaperone and signaling functions. Through a deeper mechanistic description of glucose (GLUT) transporters and multidrug resistance (MDR) antiporters, we outline novel refinements to the rocker-switch alternating-access model, such as a latch mechanism for proton-coupled monosaccharide transport. We emphasize that a full understanding of transport requires an elucidation of MFS transporter dynamics, energy landscapes, and the determination of how rate transitions are modulated by lipids. [ABSTRACT FROM AUTHOR]

High-quality evidence indicates that regular use of aspirin is effective in reducing the risk for precancerous colorectal neoplasia and colorectal cancer (CRC). This has led to US and international guidelines recommending aspirin for the primary prevention of CRC in specific populations. In this review, we summarize key questions that require addressing prior to broader adoption of aspirin-based chemoprevention, review recent evidence related to the benefits and harms of aspirin use among specific populations, and offer a rationale for precision prevention approaches. We specifically consider the mechanistic implications of evidence showing differences in aspirin's effects according to age, the potential role of modifiable mechanistic biomarkers for personalizing prevention, and emerging evidence that the gut microbiota may offer novel aspirin-associated preventive targets to reduce high-risk neoplasia. [ABSTRACT FROM AUTHOR]

Background: Concentrations of fibroblast growth factor 23 (FGF-23), a hormone that regulates phosphorus and vitamin D metabolism, increase as kidney function declines. Excess fibroblast growth factor 23 may impact brain function through promotion of vascular disease or through direct effects on neuronal tissue. Methods: In the Healthy Aging and Body Composition Study, a longitudinal observational cohort of well-functioning older adults, intact serum FGF-23 was assayed in 2,738 individuals. Cognitive function was assessed at baseline and longitudinally at years 3, 5, and 8 by administration of the Modified Mini Mental State Examination (3MSE), a test of global cognitive function, and the Digit Symbol Substitution Test (DSST), a test primarily of executive function. The associations between FGF-23 and baseline cognitive function and incident cognitive impairment were evaluated using logistic and Poisson regression respectively, and were adjusted for demographics, baseline estimated glomerular filtration rate (eGFR), urine albumin/creatinine ratio, comorbidity, and other measures of mineral metabolism including soluble klotho. Results: The mean (SD) age was 74(3) years, with 51% female, and 39% black. The median (25th, 75th) FGF-23 concentration was 47 pg/mL (37, 60). Three hundred ninety-two individuals had prevalent cognitive impairment by the 3MSE and 461 by the DSST. There was no observed association between FGF-23 and baseline cognitive function for either cognitive test. There were 277 persons with incident cognitive impairment by 3MSE, and 333 persons with incident cognitive impairment by DSST. In fully adjusted models, each two-fold higher concentration of baseline FGF-23 was not associated with incident cognitive impairment by the 3MSE (IRR = 1.02[0.88, 1.19] fully adjusted model) or by the DSST (IRR = 0.98 [0.84, 1.15]. We saw no difference when analyses were stratified by eGFR greater than or less than 60 ml/min/1.73m2. Conclusion: Intact FGF-23 was not associated with baseline cognitive function or incident cognitive impairment in this cohort well-functioning older adults. [ABSTRACT FROM AUTHOR]

The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) pandemic presents challenges to the real-time collection of population-scale data to inform near-term public health needs as well as future investigations. We established the COronavirus Pandemic Epidemiology (COPE) consortium to address this unprecedented crisis on behalf of the epidemiology research community. As a central component of this initiative, we have developed a COVID Symptom Study (previously known as the COVID Symptom Tracker) mobile application as a common data collection tool for epidemiologic cohort studies with active study participants. This mobile application collects information on risk factors, daily symptoms, and outcomes through a user-friendly interface that minimizes participant burden. Combined with our efforts within the general population, data collected from nearly 3 million participants in the United States and United Kingdom are being used to address critical needs in the emergency response, including identifying potential hot spots of disease and clinically actionable risk factors. The linkage of symptom data collected in the app with information and biospecimens already collected in epidemiology cohorts will position us to address key questions related to diet, lifestyle, environmental, and socioeconomic factors on susceptibility to COVID-19, clinical outcomes related to infection, and long-term physical, mental health, and financial sequalae. We call upon additional epidemiology cohorts to join this collective effort to strengthen our impact on the current health crisis and generate a new model for a collaborative and nimble research infrastructure that will lead to more rapid translation of our work for the betterment of public health. [ABSTRACT FROM AUTHOR]

The rapid pace of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents challenges to the robust collection of population-scale data to address this global health crisis. We established the COronavirus Pandemic Epidemiology (COPE) Consortium to unite scientists with expertise in big data research and epidemiology to develop the COVID Symptom Study, previously known as the COVID Symptom Tracker, mobile application. This application—which offers data on risk factors, predictive symptoms, clinical outcomes, and geographical hotspots—was launched in the United Kingdom on 24 March 2020 and the United States on 29 March 2020 and has garnered more than 2.8 million users as of 2 May 2020. Our initiative offers a proof of concept for the repurposing of existing approaches to enable rapidly scalable epidemiologic data collection and analysis, which is critical for a data-driven response to this public health challenge. [ABSTRACT FROM AUTHOR]

Background: Although aspirin is recommended for the prevention of colorectal cancer, the specific individuals for whom the benefits outweigh the risks are not clearly defined. Moreover, the precise mechanisms by which aspirin reduces the risk of cancer are unclear. We recently launched the ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED) trial to address these uncertainties.Methods/design: ASPIRED is a prospective, double-blind, multidose, placebo-controlled, biomarker clinical trial of aspirin use in individuals previously diagnosed with colorectal adenoma. Individuals (n = 180) will be randomized in a 1:1:1 ratio to low-dose (81 mg/day) or standard-dose (325 mg/day) aspirin or placebo. At two study visits, participants will provide lifestyle, dietary and biometric data in addition to urine, saliva and blood specimens. Stool, grossly normal colorectal mucosal biopsies and cytology brushings will be collected during a flexible sigmoidoscopy without bowel preparation. The study will examine the effect of aspirin on urinary prostaglandin metabolites (PGE-M; primary endpoint), plasma inflammatory markers (macrophage inhibitory cytokine-1 (MIC-1)), colonic expression of transcription factor binding (transcription factor 7-like 2 (TCF7L2)), colonocyte gene expression, including hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD) and those that encode Wnt signaling proteins, colonic cellular nanocytology and oral and gut microbial composition and function.Discussion: Aspirin may prevent colorectal cancer through multiple, interrelated mechanisms. The ASPIRED trial will scrutinize these pathways and investigate putative mechanistically based risk-stratification biomarkers.Trial Registration: This protocol is registered with the U.S. National Institutes of Health trial registry, ClinicalTrials.gov, under the identifier NCT02394769 . Registered on 16 March 2015. [ABSTRACT FROM AUTHOR]

Introduction: Deposition of abnormally phosphorylated tau (phospho-tau) occurs in Alzheimer's disease but also with brain ageing. The Braak staging scheme focused on neurofibrillary tangles, butabundant p-tau is also present in neuropil threads, and a recent scheme has been proposed by theBrainNet Europe consortium for staging tau pathology based on neuropil threads. We determined therelationship of threads to tangles, and the value of staging for threads in an unselected population-representative ageing brain cohort. We also determined the prevalence of astroglial tau pathologies, and their relationship to neuronal tau. Phospho-tau pathology was determined by immunohistochemistry (AT8 antibody) in the MRC-CFAS neuropathology cohort. Neuropil threads were staged using the BrainNet Europe protocol for tau pathology, and compared with Braak tangle stages. Astroglial tau pathology was assessed in neo-cortical, mesial temporal and subcortical areas. Results: Cases conformed well to the hierarchical neuropil threads staging of the BrainNet Europe protocol and correlated strongly with Braak staging (r=0.84, p < 0.001). Based on the areas under the receiver operator curves (AUC), incorporating either threads or tangle staging significantly improved dementia case identification to a similar degree over age alone (Braak stage χ² (1)=10.1, p=0.002; BNE stage χ² (1)=9.7, p=0.002). Thorn-shaped astrocytes, present in 40 % of cases, were most common in mesial temporal lobe, then brainstem, and were associated with subpial tau-positive neurites (mesial temporal: χ² (1)=61.3, p < 0.001; brainstem: χ² (1)=47.9, p < 0.001). Adding thorn astrocytes did not improve dementia prediction (AUC: χ² (1)=0.77, p=0.381), but there was a weak relationship between numbers of areas involved and staging for threads or tangles (r=0.17, p=0.023). Neuropil threads develop hierarchically in parallel with neurofibrillary tangles. Conclusions: The BrainNet Europe staging protocol is straightforward to apply, and offers similar predictive value for dementia to Braak tangle staging. Astroglial tauopathy, particularly thorn shaped astrocyte formation, does not relate to dementia status, but the association with phospho-tau neurites may suggest a pathogenic relationship to neuronal tau pathology. [ABSTRACT FROM AUTHOR]

The determination of the crystal structures of small-molecule transporters has shed light on the conformational changes that take place during structural isomerization from outward- to inward-facing states. Rather than using a simple rocking movement of two bundles around a central substrate-binding site, it has become clear that even the most simplistic transporters utilize rearrangements of nonrigid bodies. In the most dramatic cases, one bundle is fixed while the other, structurally divergent, bundle carries the substrate some 18 Å across the membrane, which in this review is termed an elevator alternating-access mechanism. Here, we compare and contrast rocker-switch, rocking-bundle, and elevator alternating-access mechanisms to highlight shared features and novel refinements to the basic alternating-access model. [ABSTRACT FROM AUTHOR]

We describe a plan to research and explore opportunities to establish an undergraduate, pre-professional degree program –Bachelor of Arts in Liberal Studies in Engineering – meant to attract students undecided about the choice of a major but who have sufficient interest to enroll in a program that keeps open the possibility that they might pursue a career in engineering. The program's core idea is to  …  take exemplary, substantive content of the traditional undergraduate engineering program – the engineering sciences, the laboratory tests, the design projects – and subject this to study from the perspectives of the humanities, arts, and social sciences as well as engineering. The method is to build on the content and form of instruction in today's engineering program but dramatically transform both content and form to achieve the goals of a liberal arts program while attending to the fundamentals of the traditional engineering course of study. To do this, ‘fundamentals' must necessarily be redefined. We illustrate what we mean by teaching ‘ …  exemplary engineering content from the perspectives of the Humanities and Social Sciences’ with three ‘modules' that students might engage in a liberal studies course or project work. Our work is meant as much to provoke a critical reflection, analysis, and broader discussion about engineering education – its relation to what engineers actually do after they graduate, and about what ought to be taken as fundamental in their education for the profession – as it is to meet the objectives of our proposals to the National Science Foundation (NSF). [ABSTRACT FROM PUBLISHER]

The state-of-the-art interpretation of stem radius changes (DRTotal) for tree water relations is based on knowledge from mostly slow growing tree species. The ratio between diurnal size fluctuations of the rigid xylem (DRXylem) and the respective fluctuations of the elastic bark (DRBark) is known to be small (<0.4) and is of importance for the localisation of water storage dynamics in stems. In this study, fast growing Eucalyptus globulus Labill. in Tasmania were investigated by point dendrometers in order to investigate tree water relations. Unexpectedly, DRXylem was found to be the main driver of DRTotal with the bark acting as a passive layer on top of the fluctuating xylem under most conditions. Accordingly, the ratio between the diurnal fluctuations of the two tissues was found to be much higher (0.6-1.6) than everything reported before. Based on simulations using a hydraulic plant model, the high tissue-specific elasticity of the Eucalyptus xylem was found to explain this atypical response and not osmotically-driven processes or species-specific flow resistances. The wide zone of secondary thickening xylem in various stages of lignification is proposed to be an important component of the high wood elasticity. The tissue acts as additional water storage like the bark and may positively affect the water transport efficiency. [ABSTRACT FROM AUTHOR]

Background and Aims: Hemodialysis (HD) patients are educated and counseled during the HD procedure. There are few studies assessing whether cognitive performance varies with dialysis. Methods: Using a randomized cross-over design, 40 patients were assigned to one of two sequences: testing 1 h before dialysis followed 1 month later by testing during the first hour of dialysis (n = 21) versus testing during the first hour of dialysis followed 1 month later by 1 h before dialysis (n = 19). Cognitive tests were administered at each testing period. Mixed regression models evaluated for a dialysis effect (difference between test performance before vs. during dialysis) while adjusting for potential learning (difference between first and second tests). Results: In models accounting for period of testing, there was no difference in test performance between 1 h before versus during the first hour of HD for all administered cognitive tests (p > 0.05). A learning effect was detected between first and second test administration in two tests, specifically, the Word List Learning and the Digit Symbol Substitution Test. Conclusions: We found no difference in cognitive performance depending on the time of testing, suggesting that cognitive tests performed during the first hour of dialysis are a valid assessment of cognitive performance. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Although cognitive impairment is common in hemodialysis patients, the etiology of and risk factors for its development remain unclear. Fibroblast growth factor 23 ( FGF-23) levels are elevated in hemodialysis patients and are associated with increased mortality and left ventricular hypertrophy. Despite FGF-23 being found within the brain, there are no prior studies assessing whether FGF-23 levels are associated with cognitive performance. We measured FGF-23 in 263 prevalent hemodialysis patients in whom comprehensive neurocognitive testing was also performed. The cross-sectional association between patient characteristics and FGF-23 levels was assessed. Principal factor analysis was used to derive two factors from cognitive test scores, representing memory and executive function, which carried a mean of 0 and a standard deviation of 1. Multivariable linear regression adjusting for age, sex, education status, and other relevant covariates was used to explore the relationship between FGF-23 and each factor. Mean age was 63 years, 46% were women and 22% were African American. The median FGF-23 level was 3098 RU/mL. Younger age, lower prevalence of diabetes, longer dialysis vintage, and higher calcium and phosphorus were independently associated with higher FGF-23 levels. Higher FGF-23 was independently associated with a lower memory score (per doubling of FGF-23, β = −0.08 SD [95% confidence interval, CI: −0.16, −0.01]) and highest quartile vs. lowest quartile (β = −0.42 SD [−0.82, −0.02]). There was no definite association of FGF 23 with executive function when examined as a continuous variable (β = −0.03 SD [−0.10, 0.04]); however, there was a trend in the quartile analysis (β = −0.28 SD [−0.63, 0.07], P = 0.13, for 4th quartile vs. 1st quartile). FGF-23 was associated with worse performance on a composite memory score, including after adjustment for measures of mineral metabolism. High FGF-23 levels in hemodialysis patients may contribute to cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: The gut microbiome is a critical modulator of host immunity and is linked to the immune response to respiratory viral infections. However, few studies have gone beyond describing broad compositional alterations in severe COVID-19, defined as acute respiratory or other organ failure. Methods: We profiled 127 hospitalized patients with COVID-19 (n = 79 with severe COVID-19 and 48 with moderate) who collectively provided 241 stool samples from April 2020 to May 2021 to identify links between COVID-19 severity and gut microbial taxa, their biochemical pathways, and stool metabolites. Results: Forty-eight species were associated with severe disease after accounting for antibiotic use, age, sex, and various comorbidities. These included significant in-hospital depletions of Fusicatenibacter saccharivorans and Roseburia hominis, each previously linked to post-acute COVID syndrome or "long COVID," suggesting these microbes may serve as early biomarkers for the eventual development of long COVID. A random forest classifier achieved excellent performance when tasked with classifying whether stool was obtained from patients with severe vs. moderate COVID-19, a finding that was externally validated in an independent cohort. Dedicated network analyses demonstrated fragile microbial ecology in severe disease, characterized by fracturing of clusters and reduced negative selection. We also observed shifts in predicted stool metabolite pools, implicating perturbed bile acid metabolism in severe disease. Conclusions: Here, we show that the gut microbiome differentiates individuals with a more severe disease course after infection with COVID-19 and offer several tractable and biologically plausible mechanisms through which gut microbial communities may influence COVID-19 disease course. Further studies are needed to expand upon these observations to better leverage the gut microbiome as a potential biomarker for disease severity and as a target for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Although tree-ring-width chronologies have been widely used for temperature reconstructions, there are many sites around the world at which there is little evidence of a clear climate signal in the ring-width chronologies. This is the case with the long-lived conifer Huon pine (Lagarostrobos franklinii (Hook. F.) Quinn), endemic to Tasmania, Australia, when the species grows at low elevation. In this study, we developed chronologies of several wood properties (e.g., tracheid radial diameter, microfibril angle) from Huon pine growing at a low-elevation site. We found that despite the absence of a climate signal in the ring-width chronologies, there were significant correlations between wood density, tracheid radial diameter and microfibril angle and temperature, stream flow and a drought index, enabling the development of robust chronologies. This novel finding suggests that chronologies based on these wood properties may have important potential for climate reconstructions from sites and species that have not yet been realized. In particular, a relatively extensive resource of ancient, low-elevation Huon pine in western Tasmania, in which climate signals have not been found using ring widths, may now be useful as part of the broader effort to reconstruct Southern Hemisphere climate. [ABSTRACT FROM AUTHOR]

The tropical conifer Callitris intratropica (Cupressaceae) produces clear annual growth rings, and has been shown to be potentially useful for understanding past climate variability in northern Australia. As climate patterns in this region become less predictable, an understanding of plant responses to different weather patterns is of importance. In this paper, we examine tree water relations using a parameter here called tree water deficit (ΔD), determined from de-trended stem size variability in densely grown (‘grove’) and isolated trees. This parameter provides an integrated measure of the trees' response to water supply and demand under constantly changing environmental conditions. The work, conducted over 12 months, found that daily variation in tree water deficit was determined mainly by soil water availability, but temperature and relative humidity contributed more to the variability over some periods. Isolated and grove trees exhibited quite distinct patterns of ΔD development during the year, but particularly during the transition between the dry and wet seasons. The results of this work suggest that the dendrochronological interpretation of tree rings in the context of strongly seasonal water availability should incorporate an understanding of the development of seasonal drought in isolated trees compared with trees experiencing strong intra-specific competition. Different responses based on the ecological situations of the trees will affect their patterns of stem growth, and ultimately the climatic information that is incorporated in ring width variability. [ABSTRACT FROM AUTHOR]

Bioelectrochemical desalination is potentially advantageous because of bioenergy production and integrated wastewater treatment and desalination. In this work, the performance and energy benefits of a liter-scale upflow microbial desalination cell (UMDC) were evaluated. The UMDC desalinated both salt solution (NaCl) and artificial seawater, and the removal rate of total dissolved solid (TDS) increased with an increased hydraulic retention time, although TDS reduction in artificial seawater was lower than that in salt solution. Our analysis suggested that electricity generation was a predominant factor in removing TDS (more than 70%), and that other factors, like water osmosis and unknown processes, also contributed to TDS reduction. It was more favorable given the high energy efficiency, when treating salt solution, to operate the UMDC under the condition of high power output compared with that of high current generation because of the amount of energy production; while high current generation was more desired with seawater desalination because of lower salinity in the effluent. Under the condition of the high power output and the assumption of the UMDC as a predesalination in connection with a reversal osmosis (RO) system, the UMDC could produce electrical energy that might potentially account for 58.1% (salt solution) and 16.5% (artificial seawater) of the energy required by the downstream RO system. Our results demonstrated the great potential of bioelectrochemical desalination. [ABSTRACT FROM AUTHOR]

PepT1 and PepT2 are major facilitator superfamily (MFS) transporters that utilize a proton gradient to drive the uptake of di- and tri-peptides in the small intestine and kidney, respectively. They are the major routes by which we absorb dietary nitrogen and many orally administered drugs. Here, we present the crystal structure of PepTSo, a functionally similar prokaryotic homologue of the mammalian peptide transporters from Shewanella oneidensis. This structure, refined using data up to 3.6 Å resolution, reveals a ligand-bound occluded state for the MFS and provides new insights into a general transport mechanism. We have located the peptide-binding site in a central hydrophilic cavity, which occludes a bound ligand from both sides of the membrane. Residues thought to be involved in proton coupling have also been identified near the extracellular gate of the cavity. Based on these findings and associated kinetic data, we propose that PepTSo represents a sound model system for understanding mammalian peptide transport as catalysed by PepT1 and PepT2. [ABSTRACT FROM AUTHOR]

Abstract: Microbial desalination cells (MDCs) hold great promise for drinking water production because of potential energy savings during the desalination process. In this study, we developed a continuously operated MDC – upflow microbial desalination cell (UMDC) for the purpose of salt removal. During the 4-month operation, the UMDC constantly removed salts and generated bio-electricity. At a hydraulic retention time (HRT) of 4days (salt solution) and current production of ∼62mA, the UMDC was able to remove more than 99% of NaCl from the salt solution that had an initial salt concentration of 30g total dissolved solids (TDS)/L. In addition, the TDS removal rate was 7.50g TDSL−1 d−1 (salt solution volume) or 5.25g TDSL−1 d−1 (wastewater volume), and the desalinated water met the drinking water standard, in terms of TDS concentration. A high charge transfer efficiency of 98.6% or 81% was achieved at HRT 1 or 4d. The UMDC produced a maximum power density of 30.8W/m3. The phenomena of bipolar electrodialysis and proton transport in the UMDC were discussed. These results demonstrated the potential of the UMDC as either a sole desalination process or a pre-desalination reactor for downstream desalination processes. [ABSTRACT FROM AUTHOR]

Abstract: In hardwoods such as Eucalyptus spp., xylem (wood) is a heterogeneous tissue consisting of multiple cell types. As such, xylem development involves multiple complex interactions. To describe and understand xylem development, and ultimately predict the resultant wood properties, a process-based approach to modelling wood property variation is potentially very useful. In this paper, a new model (CAMBIUM), which incorporates concepts of these processes, is described. CAMBIUM predicts how wood density and fibre and vessel anatomical properties vary from pith-to-bark at a daily time step as a function of changing environmental conditions and a set of simulated physiological processes. Simulations from an existing process-based model of stand development (CABALA) are used as inputs. A key feature of CAMBIUM is a model of the interaction between different xylem cell types. Some weaknesses were identified in the ability of the model to simulate vessel spatial patterns and frequencies, emphasizing the complexities inherent in this aspect of angiosperm wood formation. The model was, however, able to provide realistic estimates of short-term variation and temporal ranges in eucalypt fibre diameter and secondary wall development and wood density. [Copyright &y& Elsevier]

Using the Parliamentary Communications Allowance, MP David Drew recently conducted a large scale research project into public opinion on the British Constitution. There could not have been a better time to do so. Not only are we in the wake of severe economic and political crises, but also a period of unprecedented legislative interest in the constitution. Coordinated by Ed Leighton (an undergraduate at the LSE), the project consisted of a postal survey of 43,000 households, public debates around the constituency and workshops in local schools. The response from the public was incredible, and the results both interesting and unexpected. This article will outline some of those findings and demonstrate that large scale consultations with the public are both readily achievable and warmly welcomed. That this can all be done within the budget of the Parliamentary Communications Allowance also shows that at its best this fund can be used to genuinely engage with the public. [ABSTRACT FROM AUTHOR]

Gastrointestinal bacteria, like Escherichia coli, must remove bile acid to survive in the gut. Bile acid removal in E. coli is thought to be mediated primarily by the multidrug efflux pump, AcrB. Here, we present the structure of E. coli AcrB in complex with deoxycholate at 3.85 Å resolution. All evidence suggests that bile acid is transported out of the cell via the periplasmic vestibule of the AcrAB-TolC complex. [ABSTRACT FROM AUTHOR]

Optimizing conditions for the overexpression and purification of membrane proteins for functional and structural studies is usually a laborious and time-consuming process. This process can be accelerated using membrane protein—GFP fusions, which allows direct monitoring and visualization of membrane proteins of interest at any stage during overexpression, solubilization and purification (Fig. 1). The exceptionally stable GFP moiety of the fusion protein can be used to detect membrane proteins by observing fluorescence in whole cells during overexpression, with a detection limit as low as 10 μg of GFP per liter of culture, and in solution during solubilization and purification. Notably, the fluorescence of the GFP moiety can also be detected in standard SDS polyacrylamide gels with a detection limit of less than 5 ng of GFP per protein band (Fig. 2). In-gel fluorescence allows assessment of the integrity of membrane protein—GFP fusions and provides a rapid and generic alternative for the notoriously difficult immunoblotting of membrane proteins. With whole-cell and in-gel fluorescence the overexpression potential of many membrane protein—GFP fusions can be rapidly assessed and yields of promising targets can be improved. In this protocol the Escherichia coli BL21(DE3)-pET system—the most widely used (membrane) protein overexpression system—is used as a platform to illustrate the GFP-based method. The methodology described in this protocol can be transferred easily to other systems. [ABSTRACT FROM AUTHOR]

The bacterium Escherichia coli is one of the most popular model systems to study the assembly of membrane proteins of the so-called helix-bundle class. Here, based on this system, we review and discuss what is currently known about the assembly of these membrane proteins. In addition, we will briefly review and discuss how E. coli has been used as a vehicle for the overexpression of membrane proteins. [Copyright &y& Elsevier]

Presents the approach that allows rapid determination of the topology of Escherichia coli inner-membrane proteins by prediction method and limited fusion-protein analysis. Derivation of topology models for inner-membrane proteins; Characterization of integral membrane protein of the helix bundle class; Validity of the method.

This article presents analyses of attainment variations for five cohorts of school leavers between 1988 and 1995. Social class, ethnicity and gender variations in educational attainment at 16 are examined using data from over 80,000 young people in England and Wales. This is the only representative data set that allows analyses of educational variations in England and Wales across social class, ethnic and gender groups simultaneously. The preliminary analyses showed an underrepresentation of some ethnic and lower social class groups in the independent education sector. The attainment analyses thereafter are for state school pupils only. Between 1988 and 1995, attainment differences relating to social class, ethnicity and gender are all seen to increase. In terms of the percentages leaving compulsory schooling with five or more high grade passes (grade A*–C at General Certificate of Secondary Education), the social class gap of 50 percentage points widened to 56 percentage points, the ethnicity gap from 14 to 20 percentage points and the gender gap from 5 to 10 percentage points. The uneven improvement in educational attainment across ethnic, social class and gender groups is a cause for concern. For certain subgroups there appears to be little or no improvement over the 8 years. These findings relate to a period of considerable political intervention within the British compulsory education system. They suggest that policies focused on raising educational standards may be at variance with the aim of reducing educational inequality. [ABSTRACT FROM AUTHOR]

The Inception Horizon Hypothesis (IHH) postulates that certain stratigraphic horizons in a limestone sequence, combined with structural surfaces such as joints, provide a framework for cave development. Although subsurface and surface karst landforms are fundamentally linked, the IHH has not yet been extended to surface karstification. We tested this extension of the IHH in the world-renowned Burren karst due to its stratigraphic and structural simplicity. We used very high-resolution remote sensing datasets and detailed fieldwork to develop an updated map of the Burren's surface karst features, combined with a 3D geological model containing over 60 km of mapped cave passages. Our analysis shows that karstic connectivity between the surface and subsurface is primarily provided by a suite of vertically-persistent calcite and silica-rich veins, which form a non-stratabound fracture system across the Burren. The flow pathways provided by these veins then intersect the following inception horizons: (i) boundaries between distinct lithological units in the limestone sequence; (ii) crinoidal cycle tops, and more sporadically chert lenses, within one of those units (the Slievenaglasha Formation); (iii) thin horizons of non‑carbonates ('clay wayboards') within another unit (the Aillwee member). At the surface, the same horizons have been preferentially exploited by glacial processes, creating surfaces from which meteoric waters now recharge the subsurface and form new surface karst depressions and other karst landforms. Our new inception framework for karstification thus provides a new basis for understanding surface and subsurface connectivity in the karst critical zone in the Burren landscape, and it provides new geological insight into the functioning of carbonate critical zones more generally. [ABSTRACT FROM AUTHOR]

Represents the first longitudinal investigation of the effects of workshop participation on persistence and achievement of underrepresented minority college students enrolled in mathematics, science and engineering majors. Effect of students' interpretations of the effect of their workshop experience on academic performance and choices; California State Polytechnic University as workshop model.

Presents a study of academic quality in special education based on a survey of every faculty member in the United States in a qualifying special education doctoral program. Reputational rankings; Accounting for the variance in reputation; Ten highest ranked programs based on reputation; University of Kansas as highest ranked institution.

Cognitive impairment is a major cause of morbidity in people with chronic kidney disease (CKD) and is associated with worse survival. Prior data suggest a relationship between vascular disease and cognitive impairment in individuals with CKD. Clinicians should be aware of the high rates of cognitive impairment that occur in all stages of CKD, which, although sometimes subtle, may impact comprehension and decision making and may herald future, more debilitating impairment. [ABSTRACT FROM AUTHOR]

Tripartite ATP-independent periplasmic (TRAP) transporters are secondary-active transporters that receive their substrates via a soluble-binding protein to move bioorganic acids across bacterial or archaeal cell membranes. Recent cryo-electron microscopy (cryo-EM) structures of TRAP transporters provide a broad framework to understand how they work, but the mechanistic details of transport are not yet defined. Here we report the cryo-EM structure of the Haemophilus influenzae N-acetylneuraminate TRAP transporter (HiSiaQM) at 2.99 Å resolution (extending to 2.2 Å at the core), revealing new features. The improved resolution (the previous HiSiaQM structure is 4.7 Å resolution) permits accurate assignment of two Na+ sites and the architecture of the substrate-binding site, consistent with mutagenic and functional data. Moreover, rather than a monomer, the HiSiaQM structure is a homodimer. We observe lipids at the dimer interface, as well as a lipid trapped within the fusion that links the SiaQ and SiaM subunits. We show that the affinity (KD) for the complex between the soluble HiSiaP protein and HiSiaQM is in the micromolar range and that a related SiaP can bind HiSiaQM. This work provides key data that enhances our understanding of the 'elevator-with-an-operator' mechanism of TRAP transporters. [ABSTRACT FROM AUTHOR]

Simple Summary: Population statistics from recent years have demonstrated that rates of colorectal cancer among younger individuals have been increasing with alarming rates of mortality. This is contradictory to expectations given preventative clinical measures and suggests that there are factors that may cause greater rates of cancer in younger generations that are different than in older populations. Bacteria and other microbial organisms in the gut microbiome are crucial to human health, and research studies are beginning to demonstrate that disruptions to the gut microbiome are tied to recent increasing trends of colorectal cancer in younger populations. Traditionally considered a disease common in the older population, colorectal cancer is increasing in incidence among younger demographics. Evidence suggests that populational- and generational-level shifts in the composition of the human gut microbiome may be tied to the recent trends in gastrointestinal carcinogenesis. This review provides an overview of current research and putative mechanisms behind the rising incidence of colorectal cancer in the younger population, with insight into future interventions that may prevent or reverse the rate of early-onset colorectal carcinoma. [ABSTRACT FROM AUTHOR]

In mammals, glucose transporters (GLUT) control organism-wide blood-glucose homeostasis. In human, this is accomplished by 14 different GLUT isoforms, that transport glucose and other monosaccharides with varying substrate preferences and kinetics. Nevertheless, there is little difference between the sugar-coordinating residues in the GLUT proteins and even the malarial Plasmodium falciparum transporter PfHT1, which is uniquely able to transport a wide range of different sugars. PfHT1 was captured in an intermediate 'occluded' state, revealing how the extracellular gating helix TM7b has moved to break and occlude the sugar-binding site. Sequence difference and kinetics indicated that the TM7b gating helix dynamics and interactions likely evolved to enable substrate promiscuity in PfHT1, rather than the sugar-binding site itself. It was unclear, however, if the TM7b structural transitions observed in PfHT1 would be similar in the other GLUT proteins. Here, using enhanced sampling molecular dynamics simulations, we show that the fructose transporter GLUT5 spontaneously transitions through an occluded state that closely resembles PfHT1. The coordination of D-fructose lowers the energetic barriers between the outward- and inward-facing states, and the observed binding mode for D-fructose is consistent with biochemical analysis. Rather than a substrate-binding site that achieves strict specificity by having a high affinity for the substrate, we conclude GLUT proteins have allosterically coupled sugar binding with an extracellular gate that forms the high-affinity transition-state instead. This substrate-coupling pathway presumably enables the catalysis of fast sugar flux at physiological relevant blood-glucose concentrations. [ABSTRACT FROM AUTHOR]

Sugar porters (SPs) represent the largest group of secondary-active transporters. Some members, such as the glucose transporters (GLUTs), are well known for their role in maintaining blood glucose homeostasis in mammals, with their expression upregulated in many types of cancers. Because only a few sugar porter structures have been determined, mechanistic models have been constructed by piecing together structural states of distantly related proteins. Current GLUT transport models are predominantly descriptive and oversimplified. Here, we have combined coevolution analysis and comparative modeling, to predict structures of the entire sugar porter superfamily in each state of the transport cycle. We have analyzed the state-specific contacts inferred from coevolving residue pairs and shown how this information can be used to rapidly generate free-energy landscapes consistent with experimental estimates, as illustrated here for the mammalian fructose transporter GLUT5. By comparing many different sugar porter models and scrutinizing their sequence, we have been able to define the molecular determinants of the transport cycle, which are conserved throughout the sugar porter superfamily. We have also been able to highlight differences leading to the emergence of proton-coupling, validating, and extending the previously proposed latch mechanism. Our computational approach is transferable to any transporter, and to other protein families in general. [ABSTRACT FROM AUTHOR]

Background: Obesity is an established risk factor for colorectal cancer (CRC); but the evidence for the association is inconsistent across molecular subtypes of the disease.Methods: We pooled data on BMI, tumor microsatellite instability (MSI) status, CpG island methylator phenotype (CIMP) status, BRAF and KRAS mutations, and Jass classification types for 11,872 CRC cases and 11,013 controls from 11 observational studies. We used multinomial logistic regression to estimate odds ratio (OR) and 95% confidence intervals (CI) adjusted for covariables.Results: Higher BMI was associated with increased CRC risk (OR per 5 kg/m2, 1.18, 95%CI: 1.15-1.22). The positive association was stronger for men than women, but similar across tumor subtypes defined by individual molecular markers. In analyses by Jass type, higher BMI was associated with elevated CRC risk for types 1-4 cases but not for type 5 CRC cases (considered familial-like/Lynch syndrome MSI-H, CIMP-low/negative, BRAF-wildtype, KRAS-wildtype, OR, 1.04, 95%CI: 0.90-1.20). This pattern of associations for BMI and Jass types was consistent by sex and design of contributing studies (cohort or case-control).Conclusions: In contrast to previous reports with fewer study participants, we found limited evidence of heterogeneity for the association between BMI and CRC risk according to molecular subtype, suggesting that obesity influences nearly all major pathways involved in colorectal carcinogenesis. The null association observed for the Jass type 5 suggests that BMI is not a risk factor for the development of CRC for individuals with Lynch syndrome. [ABSTRACT FROM AUTHOR]

Introduction: Transplant centers hesitate to transplant patients with cognitive impairment. It is unclear if pre‐kidney transplant (KT) cognitive screening can predict post‐KT cognitive function. Methods: We evaluated pre‐ to post‐KT cognitive function with the Montreal Cognitive Assessment (MoCA) in a cohort of 108 patients. We used an adjusted logistic regression model to assess pre‐ to post‐KT changes in cognitive status (continuous variable) and a linear mixed model to assess changes in MoCA scores (categorical variable) pre‐ to post‐ KT. Results: The average pre‐ and post‐KT MoCA scores were 25.3 ± 3.0 and 26.4 ± 2.8, respectively. Final pre‐KT score did not predict post‐KT cognitive status (OR = 1.08; 95% CI:.92–1.26; P =.35). 32% of the patients with a final pre‐KT score ≥26 had at least one post‐KT score < 26. Conversely, 61% of the patients with a final pre‐KT score < 26 had at least one post KT score ≥26. In the linear mixed model analysis, the final pre‐KT score was associated with a small, clinically insignificant (β =.34; 95% CI:.19–.49; P <.001) effect on the post‐KT score. Conclusion: A low pre‐KT MoCA score is not a strong independent predictor of post‐KT cognitive function and should not preclude patients from receiving a KT. [ABSTRACT FROM AUTHOR]