Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of Triggerable, Trackable, and Targetable Carbon Monoxide Releasing Molecules.

ConspectusCarbon monoxide (CO) is a gaseous signaling molecule produced in humans via the breakdown of heme in an O2-dependent reaction catalyzed by heme oxygenase enzymes. A long-lived species relative to other signaling molecules (e.g., NO, H2S), CO exerts its physiological effects via binding to low-valent transition metal centers in proteins and enzymes. Studies involving the administration of low doses of CO have shown its potential as a therapeutic agent to produce vasodilation, anti-inflammatory, antiapoptotic, and anticancer effects. In pursuit of developing tools to define better the role and therapeutic potential of CO, carbon monoxide releasing molecules (CORMs) were developed. To date, the vast majority of reported CORMs have been metal carbonyl complexes, with the most well-known being Ru2Cl4(CO)6 (CORM-2), Ru(CO)3Cl(glycinate) (CORM-3), and Mn(CO)4(S2CNMe(CH2CO2H)) (CORM-401). These complexes have been used to probe the effects of CO in hundreds of cell- and animal-based experiments. However, through recent investigations, it has become evident that these reagents exhibit complicated reactivity in biological environments. The interpretation of the effects produced by some of these complexes is obscured by protein binding, such that their formulation is not clear, and by CO leakage and potential redox activity. An additional weakness with regard to CORM-2 and CORM-3 is that these compounds cannot be tracked via fluorescence. Therefore, it is unclear where or when CO release occurs, which confounds the interpretation of experiments using these molecules. To address these weaknesses, our research team has pioneered the development of metal-free CORMs based on structurally tunable extended flavonol or quinolone scaffolds. In addition to being highly controlled, with CO release only occurring upon triggering with visible light (photoCORMs), these CO donors are trackable via fluorescence prior to CO release in cellular environments and can be targeted to specific cellular locations.In the Account, we highlight the development and application of a series of structurally related flavonol photoCORMs that (1) sense characteristics of cellular environments prior to CO release; (2) enable evaluation of the influence of cytosolic versus mitochondrial-localized CO release on cellular bioenergetics; (3) probe the cytotoxicity and anti-inflammatory effects of intracellular versus extracellular CO delivery; and (4) demonstrate that albumin delivery of a photoCORM enables potent anticancer and anti-inflammatory effects. A key advantage of using triggered CO release compounds in these investigations is the ability to examine the effects of the molecular delivery vehicle in the absence and presence of localized CO release, thus providing insight into the independent contributions of CO. Overall, flavonol-based CO delivery molecules offer opportunities for triggerable, trackable, and targetable CO delivery that are unprecedented in terms of previously reported CORMs and, thus, offer significant potential for applications in biological systems.
Decoupling the effects of food and density on life history plasticity of wild animals using field experiments: insights from the steward who sits in the shadow of its tail, the North American red squirrel.

Long-term studies of wild animals provide the opportunity to investigate how phenotypic plasticity is used to cope with environmental fluctuations, and how the relationships between phenotypes and fitness can be dependent upon the ecological context. Most previous studies have only investigated life history plasticity in response to changes in temperature, yet wild animals often experience multiple environmental fluctuations simultaneously. This requires field experiments to decouple which ecological factor induces plasticity in fitness-relevant traits to better understand their population-level responses to those environmental fluctuations. For the past 32 years, we have conducted a long-term integrative study of individually marked North American red squirrels (Tamiasciurus hudsonicus Erxleben) in the Yukon, Canada. We have used multi-year field experiments to examine the physiological and life history responses of individual red squirrels to fluctuations in food abundance and conspecific density. Our long-term observational study and field experiments show that squirrels can anticipate increases in food availability and density, thereby decoupling the usual pattern where animals respond to, rather than anticipate, an ecological change. As in many other study systems, ecological factors that can induce plasticity (such as food and density) co-vary. However, our field experiments that manipulate food availability and social cues of density (frequency of territorial vocalizations) indicate that increases in social (acoustic) cues of density in the absence of additional food can induce similar life history plasticity, as does experimental food supplementation. Changes in the levels of metabolic hormones (glucocorticoids) in response to variation in food and density are one mechanism that seems to induce this adaptive life history plasticity. Although we have not yet investigated the energetic response of squirrels to elevated density or its association with life history plasticity, energetics research in red squirrels has overturned several standard pillars of knowledge in physiological ecology. We show how a tractable model species combined with integrative studies can reveal how animals cope with resource fluctuations through life history plasticity.
PCAmatchR: a flexible R package for optimal case-control matching using weighted principal components

SUMMARY A concern when conducting genome-wide association studies (GWAS) is the potential for population stratification, i.e. ancestry based genetic differences between cases and controls, that if not properly accounted for, could lead to biased association results. We developed PCAmatchR as an open source R package for performing optimal case-control matching using principal component analysis (PCA) to aid in selecting controls that are well matched by ancestry to cases. PCAmatchR takes user supplied PCA outputs and selects matching controls for cases by utilizing a weighted Mahalanobis distance metric which weights each principal component by the percent of genetic variation explained. Results from the 1000 Genomes Project data demonstrate both the functionality and performance of PCAmatchR for selecting matching controls for case populations as well as reducing inflation of association test statistics. PCAmatchR improves genomic similarity between matched cases and controls, which minimizes the effects of population stratification in GWAS analyses. AVAILABILITY PCAmatchR is freely available for download on GitHub (https://github.com/machiela-lab/PCAmatchR) or through CRAN (https://cran.r-project.org/web/packages/PCAmatchR/index.html). SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Preparation of PI/PTFE–PAI Composite Nanofiber Aerogels with Hierarchical Structure and High-Filtration Efficiency

Electrospun nanofiber, showing large specific area and high porosity, has attracted much attention across various fields, especially in the field of air filtration. The small diameter contributes to the construction of filters with high-filtration efficiency for fine particulate matter (PM), however, along with an increase in air resistance. Herein, composited nanofiber aerogels (NAs), a truly three-dimensional (3D) derivative of the densely compacted electrospun mat, were constructed with the blocks of polytetrafluoroethylene–polyamideimide (PTFE–PAI) composite nanofiber and polyimide (PI) nanofiber. PI/PTFE–PAI NAs with hierarchically porous architecture and excellent mechanical properties have been obtained by thermally induced crosslink bonding. Results indicated that sintering at 400 °C for 30 min could complete the decomposition of polyethylene (PEO) and imidization of polyamic acid (PAA) into PI, as well as generate sufficient mechanical bonding between adjacent nanofibers in the NAs without extra additive. The well-prepared PI/PTFE–PAI NAs could withstand high temperature up to 500 °C. In addition, the filtration tests illustrated that the composite NAs had an excellent performance in PM filtration. More importantly, the filtration behavior could be adjusted to meet the requirements of various applications. The excellent thermal stability and high-filtration efficiency indicated its great potential in the field of high-temperature air filtration.
A double-blind placebo controlled trial on effectiveness of prophylactic dexamethasone for preventing post- dural puncture headache after spinal anesthesia for cesarean section

Abstract Aim To determine the effect of dexamethasone in reducing post-dural puncture headache (PDPH) after spinal anesthesia for cesarean section (CS). Methods A double blind placebo controlled randomized trial of parturients undergoing CS under spinal anesthesia was conducted. Participants (n = 192) were randomly (1:1 ratio) given either 2mls (8 mg) of dexamethasone (n = 96) intravenously or 2mls of normal saline (n = 96) intravenously as placebo after clamping the umbilical cord. Visual analogue scale was used to assess the incidence and severity of PDPH on the first and fourth post-operative days. The primary outcome measure was incidence of PDPH while the secondary outcome measure was incidence of nausea and vomiting. Analysis was by intention-to-treat. Results Baseline socio-demographic and clinical variables were similar between the two groups and none of the women was lost to follow up. The incidence of PDPH (8.3% vs 25.0%; p = .002) and nausea (11.5% vs 25.0%; p = .015) were significantly lower in dexamethasone group. The severity of headache in the control groups were statistically higher on the first (p < .001) and fourth (p < .001) post-operative days. Conclusion Prophylactic dexamethasone reduces the incidence and severity of PDPH on both the first and fourth post-operative day after spinal anesthesia for CS. There was also an improvement on the incidence of nausea on the dexamethasone group compared to control.
The Role of Co-Occurrence Statistics in Developing Semantic Knowledge

The organization of our knowledge about the world into an interconnected network of concepts linked by relations profoundly impacts many facets of cognition, including attention, memory retrieval, reasoning, and learning. It is therefore crucial to understand how organized semantic representations are acquired. The present experiment investigated the contributions of readily observable environmental statistical regularities to semantic organization in childhood. Specifically, we investigated whether co-occurrence regularities with which entities or their labels more reliably occur together than with others (a) contribute to relations between concepts independently and (b) contribute to relations between concepts belonging to the same taxonomic category. Using child-directed speech corpora to estimate reliable co-occurrences between labels for familiar items, we constructed triads consisting of a target, a related distractor, and an unrelated distractor in which targets and related distractors consistently co-occurred (e.g., sock-foot), belonged to the same taxonomic category (e.g., sock-coat), or both (e.g., sock-shoe). We used an implicit, eye-gaze measure of relations between concepts based on the degree to which children (N = 72, age 4-7 years) looked at related versus unrelated distractors when asked to look for a target. The results indicated that co-occurrence both independently contributes to relations between concepts and contributes to relations between concepts belonging to the same taxonomic category. These findings suggest that sensitivity to the regularity with which different entities co-occur in children's environments shapes the organization of semantic knowledge during development. Implications for theoretical accounts and empirical investigations of semantic organization are discussed.
Foraging Ecology Differentiates Life Stages and Mercury Exposure in Common Terns (Sterna hirundo)

Some populations of common terns (Sterna hirundo) breeding at inland lakes in North America are declining, including the Laurentian Great Lakes. Terns nesting at inland colonies forage in freshwater during the breeding season and primarily in coastal marine environments during the nonbreeding season. As piscivores, they are susceptible to dietary Hg exposure. To characterize patterns of Hg exposure in this population, we 1) quantified within and among season differences in total mercury (THg) concentrations (μg/g) in blood and feathers at 2 Lake Superior breeding colonies, and 2) documented spatial and temporal variation in exposure by studying adult foraging ecology using geospatial tracking devices and stable isotopes. We used general linear models to assess the relationship between isotopic composition and THg concentrations in bird tissues relative to sex, age, colony location, and season. The THg concentrations were lowest in winter‐grown feathers (geometric mean [95% confidence limits]): 1.32 (1.09–1.59) μg/g dw (n = 60), higher at the more industrially influenced colony (chick feathers: 4.95 [4.62–5.37] μg/g dw [n = 20]), and increased with a riverine‐based diet. During the breeding season, Hg exposure varied along a gradient from lake to river, with adult females having lower blood THg concentrations than males (females: 0.83 [0.67–1.03]) μg/g ww (n = 7); males: 1.15 (0.92–1.45) μg/g ww (n = 5). Stable isotope values suggested adults obtained 42 ± 12% (n = 12) of their diet from the river during incubation, which was validated with tracking data. During chick‐rearing, chicks obtained 68 ± 19% (n = 44) of their diet from the river. Our results indicate colony location, foraging behavior, and season influenced Hg exposure for these Lake Superior colonies and underscores the importance of local contamination with respect to exposure. Integr Environ Assess Manag 2021;17:398–410. © 2020 SETAC
Learning from errors: students’ and instructors’ practices, attitudes, and beliefs

ABSTRACT In some educational contexts, such as during assessments, it is essential to avoid errors. In other contexts, however, generating an error can foster valuable learning opportunities. For instance, generating errors can improve memory for correct answers. In two surveys conducted at three large public universities in North America, we investigated undergraduate students’ and instructors’ awareness of the pedagogical benefits of generating errors, as well as related practices, attitudes, and beliefs. Surveyed topics included the incorporation of errors into learning activities, opinions about the consequences of studying errors, and approaches to feedback. Many students had an aversion towards making errors during learning and did not use opportunities to engage in errorful generation, yet studied or analysed errors when they occurred. Many instructors had a welcoming attitude towards errors that occur during learning, yet varied in providing students with resources that facilitate errorful generation. Overall, these findings reveal the prevalence of an ambivalent approach to errors: Students and instructors avoid generating errors but prioritise learning from them when they occur. These results have important implications for the implementation of pretesting, productive failure, and other error-focused learning techniques in educational contexts.
Breast Cancer Subtypes Underlying EMT-Mediated Catabolic Metabolism

Efficient catabolic metabolism of adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) is essentially required for cancer cell survival, especially in metastatic cancer progression. Epithelial–mesenchymal transition (EMT) plays an important role in metabolic rewiring of cancer cells as well as in phenotypic conversion and therapeutic resistance. Snail (SNAI1), a well-known inducer of cancer EMT, is critical in providing ATP and NADPH via suppression of several gatekeeper genes involving catabolic metabolism, such as phosphofructokinase 1 (PFK1), fructose-1,6-bisphosphatase 1 (FBP1), and acetyl-CoA carboxylase 2 (ACC2). Paradoxically, PFK1 and FBP1 are counter-opposing and rate-limiting reaction enzymes of glycolysis and gluconeogenesis, respectively. In this study, we report a distinct metabolic circuit of catabolic metabolism in breast cancer subtypes. Interestingly, PFKP and FBP1 are inversely correlated in clinical samples, indicating different metabolic subsets of breast cancer. The luminal types of breast cancer consist of the pentose phosphate pathway (PPP) subset by suppression of PFKP while the basal-like subtype (also known as triple negative breast cancer, TNBC) mainly utilizes glycolysis and mitochondrial fatty acid oxidation (FAO) by loss of FBP1 and ACC2. Notably, PPP remains active via upregulation of TIGAR in the FBP1-loss basal-like subset, indicating the importance of PPP in catabolic cancer metabolism. These results indicate different catabolic metabolic circuits and thus therapeutic strategies in breast cancer subsets.
Chitosan Modified Biochar Increases Soybean (Glycine max L.) Resistance to Salt-Stress by Augmenting Root Morphology, Antioxidant Defense Mechanisms and the Expression of Stress-Responsive Genes

Soybean is an important oilseed crop that provides high-quality protein and vegetable oil. Salinity constitutes a negative abiotic factor that reduces soybean plant growth, production, and quality. The adsorption of Na+ by chitosan-modified biochar (CMB) has a significant effect on salinity but the application of CMB is limited in soybean. In the current study, CMB was used for characterization of physiological, biochemical, and molecular responses of soybean under salt stress. Comparison of CMB and unmodified (as-is) biochar (BR) demonstrated a significant difference between them shown by using Fourier transform infrared spectroscopy (FTIR), scan electron microscopy (SEM), Brunauer–Emmett–Teller (BET), elemental analysis and z-potential measurement. Pseudo-first and second-order better suited for the analysis of Na+ adsorption kinetics. The salt-stress reduced the soybean plants growth, root architecture characteristics, biomass yield, nutrients acquisition, chlorophyll contents, soluble protein, and sugar contents, while CMB with salt-stress significantly increased the above parameters. Moreover, CMB also reduced the salinity-induced increase in the Na+, glycine betaine (GB), proline, hydrogen peroxide (H2O2), and malondialdehyde (MDA) levels in plants. The antioxidant activity and gene expression levels triggered by salinity but with the application of CMB significantly further boosted the expression profile of four genes (CAT, APX, POD and SOD) encoding antioxidant enzyme and two salt-tolerant conferring genes (GmSALT3 and CHS). Overall, these findings demonstrate the crucial role of CMB in minimizing the adverse effects of high salinity on soybean growth and efficiency of the mechanisms enabling plant protection from salinity through a shift of the architecture of the root system and enhancing the antioxidant defense systems and stress-responsive genes for achieving sustainable crop production.
Insects in high‐elevation streams: Life in extreme environments imperiled by climate change

Climate change is altering conditions in high‐elevation streams worldwide, with largely unknown effects on resident communities of aquatic insects. Here, we review the challenges of climate change for high‐elevation aquatic insects and how they may respond, focusing on current gaps in knowledge. Understanding current effects and predicting future impacts will depend on progress in three areas. First, we need better descriptions of the multivariate physical challenges and interactions among challenges in high‐elevation streams, which include low but rising temperatures, low oxygen supply and increasing oxygen demand, high and rising exposure to ultraviolet radiation, low ionic strength, and variable but shifting flow regimes. These factors are often studied in isolation even though they covary in nature and interact in space and time. Second, we need a better mechanistic understanding of how physical conditions in streams drive the performance of individual insects. Environment‐performance links are mediated by physiology and behavior, which are poorly known in high‐elevation taxa. Third, we need to define the scope and importance of potential responses across levels of biological organization. Short‐term responses are defined by the tolerances of individuals, their capacities to perform adequately across a range of conditions, and behaviors used to exploit local, fine‐scale variation in abiotic factors. Longer term responses to climate change, however, may include individual plasticity and evolution of populations. Whether high‐elevation aquatic insects can mitigate climatic risks via these pathways is largely unknown.
Prospective evaluation of the lymph node proteome in dogs with multicentric lymphoma supplemented with sulforaphane

Abstract Background Lymphoma (LSA) is a common malignancy in dogs. Epigenetic changes are linked to LSA pathogenesis and poor prognosis in humans, and LSA pathogenesis in dogs. Sulforaphane (SFN), an epigenetic‐targeting compound, has recently gained interest in relation to cancer prevention and therapy. Objective Examine the impact of oral supplementation with SFN on the lymph node proteome of dogs with multicentric LSA. Animals Seven client‐owned dogs with multicentric LSA. Methods Prospective, nonrandomized, noncontrolled study in treatment‐naïve dogs with intermediate or large cell multicentric LSA. Lymph node cell aspirates were obtained before and after 7 days of oral supplementation with SFN, and analyzed via label‐free mass spectrometry, immunoblots, and Gene Set Enrichment Analysis. Results There was no clinical response and no adverse events attributed to SFN. For individual dogs, the expression of up to 650 proteins changed by at least 2‐fold (range, 2‐100) after supplementation with SFN. When all dogs where analyzed together, 14 proteins were significantly downregulated, and 10 proteins were significantly upregulated after supplementation with SFN (P < .05). Proteins and gene sets impacted by SFN were commonly involved in immunity, response to oxidative stress, gene transcription, apoptosis, protein transport, maturation and ubiquitination. Conclusions and Clinical Importance Sulforaphane is associated with major changes in the proteome of neoplastic lymphocytes in dogs.