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This preliminary study developed a novel cellulose pretreatment method for cost-effective cellulosic utilization using a modified cuprammonium solution as a solvent to dissolve cellulose followed by molecular oxygen/Fenton depolymerization. The modified cuprammonium solution is composed of cuprammonium solution and a special catalyst that could efficiently enhance cellulosic oxygen sensitivity and therefore improve cellulosic depolymerization. The molecular oxygen depolymerization and Fenton depolymerization of cellulosic biomass dissolved in the modified cuprammonium solution were investigated. The results demonstrate that the Fenton reaction efficiently depolymerized the cellulose dissolved in the modified cuprammonium solution and reached the monomers with no loss of organic carbon, and almost all the cellulose maintained solubility without reagglomeration after cuprammonium was removed. Molecular oxygen oxidation reduced the cellulose average degree of polymerization (DP) to approximately 4 with less cost, and the oxygen pre-oxidation increased the H2O2 utilization in the Fenton depolymerization and remarkably reduced the H2O2 requirement.

Process-based land surface models are important tools for estimating global wetland methane (CH4) emissions and projecting their behavior across space and time. So far there are no performance assessments of model responses to drivers at multiple time scales. In this study, we apply wavelet analysis to identify the dominant time scales contributing to model uncertainty in the frequency domain. We evaluate seven wetland models at 23 eddy covariance tower sites. Our study first characterizes site-level patterns of freshwater wetland CH4 fluxes (FCH4) at different time scales. A Monte Carlo approach was developed to incorporate flux observation error to avoid misidentification of the time scales that dominate model error. Our results suggest that (a) significant model-observation disagreements are mainly at multi-day time scales (32 days) for the boreal and Arctic tundra wetland sites but have significant bias in variability at seasonal time scales for temperate and tropical/subtropical sites; (c) model errors exhibit increasing power spectrum as time scale increases, indicating that biases at time scales

Wetlands are responsible for 20%–31% of global methane (CH4) emissions and account for a large source of uncertainty in the global CH4 budget. Data-driven upscaling of CH4 fluxes from eddy covariance measurements can provide new and independent bottom-up estimates of wetland CH4 emissions. Here, we develop a six-predictor random forest upscaling model (UpCH4), trained on 119 site-years of eddy covariance CH4 flux data from 43 freshwater wetland sites in the FLUXNET-CH4 Community Product. Network patterns in site-level annual means and mean seasonal cycles of CH4 fluxes were reproduced accurately in tundra, boreal, and temperate regions (Nash-Sutcliffe Efficiency ∼0.52–0.63 and 0.53). UpCH4 estimated annual global wetland CH4 emissions of 146 ± 43 TgCH4 y−1 for 2001–2018 which agrees closely with current bottom-up land surface models (102–181 TgCH4 y−1) and overlaps with top-down atmospheric inversion models (155–200 TgCH4 y−1). However, UpCH4 diverged from both types of models in the spatial pattern and seasonal dynamics of tropical wetland emissions. We conclude that upscaling of eddy covariance CH4 fluxes has the potential to produce realistic extra-tropical wetland CH4 emissions estimates which will improve with more flux data. To reduce uncertainty in upscaled estimates, researchers could prioritize new wetland flux sites along humid-to-arid tropical climate gradients, from major rainforest basins (Congo, Amazon, and SE Asia), into monsoon (Bangladesh and India) and savannah regions (African Sahel) and be paired with improved knowledge of wetland extent seasonal dynamics in these regions. The monthly wetland methane products gridded at 0.25° from UpCH4 are available via ORNL DAAC (https://doi.org/10.3334/ORNLDAAC/2253).

Purpose. Aerobic exercise has been found to be neuroprotective in animal models of retinal degeneration. This study aims to report physical activity levels in patients with RP and investigate the relationship between physical activity and vision-related quality-of-life (QOL). Materials and Methods. A retrospective study of adult patients with RP examined in 2005–2014. Physical activity levels were assessed using the Godin Exercise Questionnaire. The NEI-Visual Function Questionaire-25 (VFQ-25), SF-36 General Health survey, and Pepper Assessment Tool for Disability (PAT-D) were administered. Results. 143 patients participated. 81 (56.6%) patients were classified as “active” and 62 (43.4%) as “insufficiently active” by Godin score. VFQ-25 revealed statistically significant differences between the active and insufficiently active patients, including overall visual function (53.3 versus 45.1, p=0.010), color vision (73.8 versus 52.9, p

Translocation sequencing can be used to assess mechanisms of DNA repair and identify genome-wide double-strand breaks (DSBs) accessible to DNA repair machinery. Here, we present a protocol for mapping double-strand DNA break sites across the genome with translocation capture sequencing. Bait DSBs are introduced using a Cas9 nuclease and repaired by the host cell, connecting bait DSBs to other DSBs. Repair sites are detected by isolating bait site DNA, cleaving normal sequence to enrich off-site repair, and next-generation sequencing. For complete details on the use and execution of this protocol, please refer to Switonski et al. (2021).1.

Recent studies have shown that during unimanual motor tasks, aging adults show bilateral recruitment of primary motor cortex (M1), while younger adults show a suppression of the ipsilateral motor cortex. Additional work has indicated that increased bilateral M1 recruitment in older adults may be deleterious when performing some motor tasks. However, higher levels of physical fitness are associated with improved dexterity and fitness may mitigate the loss of both inhibitory and excitatory communication in aging adults. The goal of this study was to assess dexterity and interhemispheric motor communication in physically fit and sedentary middle-age (40–60 years) right handed participants using tests of hand deftness and transcranial magnetic stimulation (TMS). To behaviorally assess the influence of interhemispheric communication on motor performance, participants also perform the coin rotation deftness task while maintaining pinch force with the opposite hand (bimanual condition). We correlated these behavioral measures with the ipsilateral silent period using TMS to assess interhemispheric inhibition. Our results show that the middle-aged adults who were physically fit had better dexterity of their right hand (finger tapping and peg-board). When performing the coin rotation task the fit group had no between hand differences, but the sedentary group’s left hand performance was inferior to the their right hand. We found that better dexterity correlated with ipsilateral silent period duration (greater inhibition) thereby supporting the postulate that fitness improves interhemispheric motor communication.

The effects of aging on rehabilitation of aging-related diseases are rarely a design consideration in rehabilitation research. In this brief review we present strong coincidental evidence from these two fields suggesting that deficits in aging-related disease or injury are compounded by the interaction between aging-related brain changes and disease-related brain changes. Specifically, we hypothesize that some aphasia, motor, and neglect treatments using repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in stroke patients may address the aging side of this interaction. The importance of testing this hypothesis and addressing the larger aging by aging-related disease interaction is discussed. Underlying mechanisms in aging that most likely are relevant to rehabilitation of aging-related diseases also are covered.

Increasing atmospheric methane (CH _4 ) concentrations have contributed to approximately 20% of anthropogenic climate change. Despite the importance of CH _4 as a greenhouse gas, its atmospheric growth rate and dynamics over the past two decades, which include a stabilization period (1999–2006), followed by renewed growth starting in 2007, remain poorly understood. We provide an updated estimate of CH _4 emissions from wetlands, the largest natural global CH _4 source, for 2000–2012 using an ensemble of biogeochemical models constrained with remote sensing surface inundation and inventory-based wetland area data. Between 2000–2012, boreal wetland CH _4 emissions increased by 1.2 Tg yr ^−1 (−0.2–3.5 Tg yr ^−1 ), tropical emissions decreased by 0.9 Tg yr ^−1 (−3.2−1.1 Tg yr ^−1 ), yet globally, emissions remained unchanged at 184 ± 22 Tg yr ^−1 . Changing air temperature was responsible for increasing high-latitude emissions whereas declines in low-latitude wetland area decreased tropical emissions; both dynamics are consistent with features of predicted centennial-scale climate change impacts on wetland CH _4 emissions. Despite uncertainties in wetland area mapping, our study shows that global wetland CH _4 emissions have not contributed significantly to the period of renewed atmospheric CH _4 growth, and is consistent with findings from studies that indicate some combination of increasing fossil fuel and agriculture-related CH _4 emissions, and a decrease in the atmospheric oxidative sink.

Cells respond to accumulation of misfolded proteins in the endoplasmic reticulum (ER) by activating the unfolded protein response (UPR) signaling pathway. The UPR restores ER homeostasis by degrading misfolded proteins, inhibiting translation, and increasing expression of chaperones that enhance ER protein folding capacity. Although ER stress and protein aggregation have been implicated in aging, the role of UPR signaling in regulating lifespan remains unknown. Here we show that deletion of several UPR target genes significantly increases replicative lifespan in yeast. This extended lifespan depends on a functional ER stress sensor protein, Ire1p, and is associated with constitutive activation of upstream UPR signaling. We applied ribosome profiling coupled with next generation sequencing to quantitatively examine translational changes associated with increased UPR activity and identified a set of stress response factors up-regulated in the long-lived mutants. Besides known UPR targets, we uncovered up-regulation of components of the cell wall and genes involved in cell wall biogenesis that confer resistance to multiple stresses. These findings demonstrate that the UPR is an important determinant of lifespan that governs ER stress and identify a signaling network that couples stress resistance to longevity.

Declines in freshwater quality resulting from anthropogenic nutrient input remain a persistent issue worldwide. Yet, we still have a limited understanding of the magnitude and scale at which most lakes have been affected by human activities, namely Land Use/Land Cover (LULC) alterations. In response, the NSERC Canadian Lake Pulse Network has compiled the first nationwide systematic database of lake quality metrics by surveying 664 lakes across 12 ecozones over 3 years. To assess the influence of catchment development on water quality and its spatial variation, we built generally additive models and multivariate regressions to quantify the association between watershed LULC and lake temperature, Secchi depth, as well as chlorophyll-a, limiting nutrient, and ion concentrations. We found that agricultural and urban land use explained the greatest proportion of variation in water quality among LULC categories ([R.sup.2] = 0.20-0.29). Overall, our study highlights that drivers of water quality are similar across regions; however, baseline conditions vary, so freshwater ecosystem management strategies must consider their geographic context to better predict where water quality thresholds will be surpassed. Key words: agriculture, eutrophication, lake, multivariate regression tree, water quality, Introduction Despite decades of research into the drivers of lake water quality and evolving land management strategies, cultural eutrophication remains one of the leading threats to freshwater ecosystems across the [...]

Physical Fitness has been long associated with maintenance and improvement of motor performance as we age. In particular, measures of psychomotor speed and motor dexterity tend to be higher in physically fit aging adults as compared to their sedentary counterparts. Using functional magnetic resonance imaging and transcranial magnetic stimulation, we explored the patterns of neural activity that may, in part, account for differences between individuals of varying physical fitness levels. In this study, we enrolled both sedentary and physically fit middle age (40-60) and younger (18-30) adults and measured upper extremity motor performance during behavioral testing. In a follow-up session, we employed TMS and fMRI to assess levels of interhemispheric communication during unimanual tasks. Results show that increased physical fitness is associated with better upper extremity motor performance on distal dexterity assessments and increased levels of interhemispheric inhibition in middle-age adults. Further, the functional correlates of changes of ipsilateral activity appears to be restricted to the aging process as younger adults of varying fitness levels do not differ in hemispheric patterns of activity or motor performance. We conclude that sedentary aging confers a loss of interhemispheric inhibition that is deleterious to some aspects of motor function, as early as midlife, but these changes can be mediated by chronic engagement in aerobic exercise.

Research antibodies are used in a wide range of bioscience disciplines, yet it is common to hear dissatisfaction amongst researchers with respect to their quality. Although blame is often attributed to the manufacturers, scientists are not doing all they can to help themselves. One example of this is in the reporting of research antibody use. Publications routinely lack key details, including the host species, code number and even the company who supplied the antibody. Authors also fail to demonstrate that validation of the antibodies has taken place. These omissions make it harder for reviewers to establish the likely reliability of the results and for researchers to reproduce the experiments. The scale of this problem, combined with high profile concerns about experimental reproducibility, has caused the Nature Publishing Group to include a section on antibody information in their recent Reporting Checklist for Life Science Articles. In this commentary we consider the issue of reporting research antibody use and ask what details authors should be including in their publications to improve experimental reproducibility.

Introduction: Since the development of the 10 item Purdue Pharmacist Directive Guidance (PPDG) Scale several studies of the psychometric properties of the PPDG have been conducted. Although Cronbach's alpha was calculated as a means of internal consistency reliability, a demonstration of the mean centering of the individual items from the instrument were not explored. Objectives: This study focused on investigating the mean stabilization of items within the PPDG as they pertain to Cronbach's reliability coefficient calculation. Methods: Using item analysis procedures in SPSS, the mean stability of items within the general factor of directive guidance and subscales of instruction and feedback and goal setting were examined for the PPDG. Results: Mean stability scores for entire PPDG scale and the subscales of instruction and feedback and goal setting were strong. Also, corrected item-total correlations and Cronbach's alphas following item deletion were good for the overall PPDG scale and the subscales. Conclusions: The results provide evidence to enhance understanding of the psychometric stability of the PPDG scale and its subscales. Type: Original Research

Embodied/modality-specific theories of semantic memory propose that sensorimotor representations play an important role in perception and action. A large body of evidence supports the notion that concepts involving human motor action (i.e., semantic-motor representations) are processed in both language and motor regions of the brain. However, most studies have focused on perceptual tasks, leaving unanswered questions about language-motor interaction during production tasks. Thus, we investigated the effects of shared semantic-motor representations on concurrent language and motor production tasks in healthy young adults, manipulating the semantic task (motor-related vs. nonmotor-related words) and the motor task (i.e., standing still and finger-tapping). In Experiment 1 (n = 20), we demonstrated that motor-related word generation was sufficient to affect postural control. In Experiment 2 (n = 40), we demonstrated that motor-related word generation was sufficient to facilitate word generation and finger tapping. We conclude that engaging semantic-motor representations can have a reciprocal influence on motor and language production. Our study provides additional support for functional language-motor interaction, as well as embodied/modality-specific theories.

Aging is characterized by the accumulation of damaged cellular macromolecules caused by declining repair and elimination pathways. An integral component employed by cells to counter toxic protein aggregates is the conserved ubiquitin/proteasome system (UPS). Previous studies have described an age-dependent decline of proteasomal function and increased longevity correlates with sustained proteasome capacity in centenarians and in naked mole rats, a long-lived rodent. Proof for a direct impact of enhanced proteasome function on longevity, however, is still lacking. To determine the importance of proteasome function in yeast aging, we established a method to modulate UPS capacity by manipulating levels of the UPS-related transcription factor Rpn4. While cells lacking RPN4 exhibit a decreased non-adaptable proteasome pool, loss of UBR2, an ubiquitin ligase that regulates Rpn4 turnover, results in elevated Rpn4 levels, which upregulates UPS components. Increased UPS capacity significantly enhances replicative lifespan (RLS) and resistance to proteotoxic stress, while reduced UPS capacity has opposing consequences. Despite tight transcriptional co-regulation of the UPS and oxidative detoxification systems, the impact of proteasome capacity on lifespan is independent of the latter, since elimination of Yap1, a key regulator of the oxidative stress response, does not affect lifespan extension of cells with higher proteasome capacity. Moreover, since elevated proteasome capacity results in improved clearance of toxic huntingtin fragments in a yeast model for neurodegenerative diseases, we speculate that the observed lifespan extension originates from prolonged elimination of damaged proteins in old mother cells. Epistasis analyses indicate that proteasome-mediated modulation of lifespan is at least partially distinct from dietary restriction, Tor1, and Sir2. These findings demonstrate that UPS capacity determines yeast RLS by a mechanism that is distinct from known longevity pathways and raise the possibility that interventions to promote enhanced proteasome function will have beneficial effects on longevity and age-related disease in humans.

The ongoing development of the Global Carbon Project (GCP) global methane (CH4 ) budget shows a continuation of increasing CH4 emissions and CH4 accumulation in the atmosphere during 2000-2017. Here, we decompose the global budget into 19 regions (18 land and 1 oceanic) and five key source sectors to spatially attribute the observed global trends. A comparison of top-down (TD) (atmospheric and transport model-based) and bottom-up (BU) (inventory- and process model-based) CH4 emission estimates demonstrates robust temporal trends with CH4 emissions increasing in 16 of the 19 regions. Five regions-China, Southeast Asia, USA, South Asia, and Brazil-account for >40% of the global total emissions (their anthropogenic and natural sources together totaling >270 Tg CH4  yr-1 in 2008-2017). Two of these regions, China and South Asia, emit predominantly anthropogenic emissions (>75%) and together emit more than 25% of global anthropogenic emissions. China and the Middle East show the largest increases in total emission rates over the 2000 to 2017 period with regional emissions increasing by >20%. In contrast, Europe and Korea and Japan show a steady decline in CH4 emission rates, with total emissions decreasing by ~10% between 2000 and 2017. Coal mining, waste (predominantly solid waste disposal) and livestock (especially enteric fermentation) are dominant drivers of observed emissions increases while declines appear driven by a combination of waste and fossil emission reductions. As such, together these sectors present the greatest risks of further increasing the atmospheric CH4 burden and the greatest opportunities for greenhouse gas abatement.

A common mechanism in inherited ataxia is a vulnerability of DNA damage. Spinocerebellar ataxia type 7 (SCA7) is a CAG-polyglutamine-repeat disorder characterized by cerebellar and retinal degeneration. Polyglutamine-expanded ataxin-7 protein incorporates into STAGA co-activator complex and interferes with transcription by altering histone acetylation. We performed chromatic immunoprecipitation sequencing ChIP-seq on cerebellum from SCA7 mice and observed increased H3K9-promoter acetylation in DNA repair genes, resulting in increased expression. After detecting increased DNA damage in SCA7 cells, mouse primary cerebellar neurons, and patient stem-cell-derived neurons, we documented reduced homology-directed repair (HDR) and single-strand annealing (SSA). To evaluate repair at endogenous DNA in native chromosome context, we modified linear amplification-mediated high-throughput genome-wide translocation sequencing and found that DNA translocations are less frequent in SCA7 models, consistent with decreased HDR and SSA. Altered DNA repair function in SCA7 may predispose the subject to excessive DNA damage, leading to neuron demise and highlights DNA repair as a therapy target.

Ref.: Can. J. Fish. Aquat. Sci. 00:1-13(2023) | dx.doi.org/10.11 39/cjfas-2023-0109. In Fig. 4 of the originally published article, the units for the bottom row of graphs were listed in [micro]g/L, [...]

Introduction: Since the development of the 10 item Purdue Pharmacist Directive Guidance (PPDG) Scale several studies of the psychometric properties of the PPDG have been conducted. Although Cronbach’s alpha was calculated as a means of internal consistency reliability, a demonstration of the mean centering of the individual items from the instrument were not explored.Objectives: This study focused on investigating the mean stabilization of items within the PPDG as they pertain to Cronbach’s reliability coefficient calculation.Methods:Using item analysis procedures in SPSS, the mean stability of items within the general factor of directive guidance and subscales of instruction and feedback and goal setting were examined for the PPDG.Results:Mean stability scores for entire PPDG scale and the subscales of instruction and feedback and goal setting were strong. Also, corrected item-total correlations and Cronbach’s alphas following item deletion were good for the overall PPDG scale and the subscales.Conclusions: The results provide evidence to enhance understanding of the psychometric stability of the PPDG scale and its subscales.

While wetlands are the largest natural source of methane (CH4 ) to the atmosphere, they represent a large source of uncertainty in the global CH4 budget due to the complex biogeochemical controls on CH4 dynamics. Here we present, to our knowledge, the first multi-site synthesis of how predictors of CH4 fluxes (FCH4) in freshwater wetlands vary across wetland types at diel, multiday (synoptic), and seasonal time scales. We used several statistical approaches (correlation analysis, generalized additive modeling, mutual information, and random forests) in a wavelet-based multi-resolution framework to assess the importance of environmental predictors, nonlinearities and lags on FCH4 across 23 eddy covariance sites. Seasonally, soil and air temperature were dominant predictors of FCH4 at sites with smaller seasonal variation in water table depth (WTD). In contrast, WTD was the dominant predictor for wetlands with smaller variations in temperature (e.g., seasonal tropical/subtropical wetlands). Changes in seasonal FCH4 lagged fluctuations in WTD by ~17 ± 11 days, and lagged air and soil temperature by median values of 8 ± 16 and 5 ± 15 days, respectively. Temperature and WTD were also dominant predictors at the multiday scale. Atmospheric pressure (PA) was another important multiday scale predictor for peat-dominated sites, with drops in PA coinciding with synchronous releases of CH4 . At the diel scale, synchronous relationships with latent heat flux and vapor pressure deficit suggest that physical processes controlling evaporation and boundary layer mixing exert similar controls on CH4 volatilization, and suggest the influence of pressurized ventilation in aerenchymatous vegetation. In addition, 1- to 4-h lagged relationships with ecosystem photosynthesis indicate recent carbon substrates, such as root exudates, may also control FCH4. By addressing issues of scale, asynchrony, and nonlinearity, this work improves understanding of the predictors and timing of wetland FCH4 that can inform future studies and models, and help constrain wetland CH4 emissions.

MLL gene rearrangements (MLLr) are a common cause of aggressive, incurable acute lymphoblastic leukemias (ALL) in infants and children, most of which originate in utero. The most common MLLr produces an MLL-AF4 fusion protein. MLL-AF4 promotes leukemogenesis by activating key target genes, mainly through recruitment of DOT1L and increased histone H3 lysine-79 methylation (H3K79me2/3). One key MLL-AF4 target gene is PROM1, which encodes CD133 (Prominin-1). CD133 is a pentaspan transmembrane glycoprotein that represents a potential pan-cancer target as it is found on multiple cancer stem cells. Here we demonstrate that aberrant PROM1/CD133 expression is essential for leukemic cell growth, mediated by direct binding of MLL-AF4. Activation is controlled by an intragenic H3K79me2/3 enhancer element (KEE) leading to increased enhancer-promoter interactions between PROM1 and the nearby gene TAPT1. This dual locus regulation is reflected in a strong correlation of expression in leukemia. We find that in PROM1/CD133 non-expressing cells, the PROM1 locus is repressed by polycomb repressive complex 2 (PRC2) binding, associated with reduced expression of TAPT1, partially due to loss of interactions with the PROM1 locus. Together, these results provide the first detailed analysis of PROM1/CD133 regulation that explains CD133 expression in MLLr ALL.

Autophagy, particularly with BECN1, has paradoxically been highlighted as tumor promoting in Ras-driven cancers, but potentially tumor suppressing in breast and ovarian cancers. However, studying the specific role of BECN1 at the genetic level is complicated due to its genomic proximity to BRCA1 on both human (chromosome 17) and murine (chromosome 11) genomes. In human breast and ovarian cancers, the monoallelic deletion of these genes is often co-occurring. To investigate the potential tumor suppressor roles of two of the most commonly deleted autophagy genes in ovarian cancer, BECN1 and MAP1LC3B were knocked-down in atypical (BECN1+/+ and MAP1LC3B+/+) ovarian cancer cells. Ultra-performance liquid chromatography mass-spectrometry metabolomics revealed reduced levels of acetyl-CoA which corresponded with elevated levels of glycerophospholipids and sphingolipids. Migration rates of ovarian cancer cells were increased upon autophagy gene knockdown. Genomic instability was increased, resulting in copy-number alteration patterns which mimicked high grade serous ovarian cancer. We further investigated the causal role of Becn1 haploinsufficiency for oncogenesis in a MISIIR SV40 large T antigen driven spontaneous ovarian cancer mouse model. Tumors were evident earlier among the Becn1+/- mice, and this correlated with an increase in copy-number alterations per chromosome in the Becn1+/- tumors. The results support monoallelic loss of BECN1 as permissive for tumor initiation and potentiating for genomic instability in ovarian cancer.

Recent stroke studies have shown that the ipsi-lesional thalamus longitudinally and significantly decreases after stroke in the acute and subacute stages. However, additional considerations in the chronic stages of stroke require exploration including time since stroke, gender, intracortical volume, aging, and lesion volume to better characterize thalamic differences after cortical infarct. This cross-sectional retrospective study quantified the ipsilesional and contralesional thalamus volume from 69 chronic stroke subjects' anatomical MRI data (age 35-92) and related the thalamus volume to time since stroke, gender, intracortical volume, age, and lesion volume. The ipsi-lesional thalamus volume was significantly smaller than the contra-lesional thalamus volume (t(68) = 13.89, p