Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural, mutagenic and in silico studies of xyloglucan fucosylation in Arabidopsis thaliana suggest a water‐mediated mechanism

The mechanistic underpinnings of the complex process of plant polysaccharide biosynthesis are poorly understood, largely because of the resistance of glycosyltransferase (GT) enzymes to structural characterization. In Arabidopsis thaliana, a glycosyl transferase family 37 (GT37) fucosyltransferase 1 (AtFUT1) catalyzes the regiospecific transfer of terminal 1,2-fucosyl residues to xyloglucan side chains - a key step in the biosynthesis of fucosylated sidechains of galactoxyloglucan. We unravel the mechanistic basis for fucosylation by AtFUT1 with a multipronged approach involving protein expression, X-ray crystallography, mutagenesis experiments and molecular simulations. Mammalian cell culture expressions enable the sufficient production of the enzyme for X-ray crystallography, which reveals the structural architecture of AtFUT1 in complex with bound donor and acceptor substrate analogs. The lack of an appropriately positioned active site residue as a catalytic base leads us to propose an atypical water-mediated fucosylation mechanism facilitated by an H-bonded network, which is corroborated by mutagenesis experiments as well as detailed atomistic simulations.
The Survival Advantage of “Supratotal” Resection of Glioblastoma Using Selective Cortical Mapping and the Subpial Technique

BACKGROUND A substantial body of evidence suggests that cytoreductive surgery is a prerequisite to prolonging survival in patients with glioblastoma (GBM). OBJECTIVE To evaluate the safety and impact of "supratotal" resections beyond the zone of enhancement seen on magnetic resonance imaging scans, using a subpial technique. METHODS We retrospectively evaluated 86 consecutive patients with primary GBM, managed by the senior author, using a subpial resection technique with or without carmustine (BCNU) wafer implantation. Multivariate Cox proportional hazards regression was used to analyze clinical, radiological, and outcome variables. Overall impacts of extent of resection (EOR) and BCNU wafer placement were compared using Kaplan-Meier survival analysis. RESULTS Mean patient age was 56 years. The median OS for the group was 18.1 months. Median OS for patients undergoing gross total, near-total, and subtotal resection were 54, 16.5, and 13.2 months, respectively. Patients undergoing near-total resection ( P = .05) or gross total resection ( P < .01) experienced statistically significant longer survival time than patients undergoing subtotal resection as well as patients undergoing ≥95% EOR ( P < .01) when compared to <95% EOR. The addition of BCNU wafers had no survival advantage. CONCLUSIONS The subpial technique extends the resection beyond the contrast enhancement and is associated with an overall survival beyond that seen in similar series where resection of the enhancement portion is performed. The effect of supratotal resection on survival exceeded the effects of age, Karnofsky performance score, and tumor volume. A prospective study would help to quantify the impact of the subpial technique on quality of life and survival as compared to a traditional resection limited to the enhancing tumor.
The protective effect of PFTα on alcohol-induced osteonecrosis of the femoral head

Epidemiologic studies have shown alcohol plays a pivotal role in the development of osteonecrosis of the femoral head (ONFH). The aim of this study was to explore the underlying mechanism of alcohol-induced ONFH and the protective effect of pifithrin-α (PFTα). In vitro, we found ethanol treatment significantly activated p53, suppressed Wnt/β-catenin signaling and inhibited osteogenic-related proteins. Furthermore, by separating the cytoplasmic and nuclear proteins, we found ethanol inhibited osteogenesis by impairing the accumulation of β-catenin in both the cytoplasm and nucleus in human bone mesenchymal stem cells (hBMSCs), which resulted from activating glycogen synthase kinase-3β (GSK-3β). Therefore, PFTα, a p53 inhibitor, was introduced in this study to block the ethanol-triggered activation of p53 in hBMSCs and alcohol-induced ONFH in a rat model. In vivo, we established alcohol-induced ONFH in rats and investigated the protective effect of PFTα. Hematoxylin & eosin (H&E) staining combined with TdT-mediated dUTP nick end labeling (TUNEL), cleaved caspase-3 immunohistochemical staining, and micro-CT images revealed substantial ONFH in the alcohol-administered rats, whereas significantly less osteonecrosis developed in the rats injected with PFTα. Osteogenic-related proteins, including osteocalcin, osteopontin and collagen I, were significantly decreased in the alcohol-administered rats, whereas these results were reversed in the PFTα-injected rats. Fluorochrome labeling similarly showed that alcohol significantly reduced the osteogenic activity in the rat femoral head, which was blocked by the injection of PFTα. In conclusion, PFTα had an antagonistic effect against the effects of ethanol on hBMSCs and could be a clinical strategy to prevent the development of alcohol-induced ONFH.
Discovery of a Novel Microsomal Epoxide Hydrolase–Catalyzed Hydration of a Spiro Oxetane

Oxetane moieties are increasingly being used by the pharmaceutical industry as building blocks in drug candidates because of their pronounced ability to improve physicochemical parameters and metabolic stability of drug candidates. The enzymes that catalyze the biotransformation of the oxetane moiety are, however, not well studied. The in vitro metabolism of a spiro oxetane-containing compound AZD1979 [(3-(4-(2-oxa-6-azaspiro[3.3]heptan-6-ylmethyl)phenoxy)azetidin-1-yl)(5-(4-ethoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone] was studied and one of its metabolites, M1, attracted our interest because its formation was NAD(P)H independent. The focus of this work was to elucidate the structure of M1 and to understand the mechanism(s) of its formation. We established that M1 was formed via hydration and ring opening of the oxetanyl moiety of AZD1979. Incubations of AZD1979 using various human liver subcellular fractions revealed that the hydration reaction leading to M1 occurred mainly in the microsomal fraction. The underlying mechanism as a hydration, rather than an oxidation reaction, was supported by the incorporation of 18O from H218O into M1. Enzyme kinetics were performed probing the formation of M1 in human liver microsomes. The formation of M1 was substantially inhibited by progabide, a microsomal epoxide hydrolase inhibitor, but not by trans-4-[4-(1-adamantylcarbamoylamino)cyclohexyloxy]benzoic acid, a soluble epoxide hydrolase inhibitor. On the basis of these results, we propose that microsomal epoxide hydrolase catalyzes the formation of M1. The substrate specificity of microsomal epoxide hydrolase should therefore be expanded to include not only epoxides but also the oxetanyl ring system present in AZD1979.
Frog tendon structure and its relationship with locomotor modes

Tendon collagen fibrils are the basic force‐transmitting units of the tendon. Yet, surprisingly little is known about the diversity in tendon anatomy and ultrastructure, and the possible relationships between this diversity and locomotor modes utilized. Our main objectives were to investigate: (a) the ultra‐structural anatomy of the tendons in the digits of frogs; (b) the diversity of collagen fibril diameters across frogs with different locomotor modes; (c) the relationship between morphology, as expressed by the morphology of collagen fibrils and tendons, and locomotor modes. To assess the relationship between morphology and the locomotor modes of the sampled taxa we performed a principal component analysis considering body length, fibrillar cross sectional area (CSA) and tendon CSA. A MANOVA showed that differences between species with different locomotor modes were significant with collagen fibril diameter being the discriminating factor. Overall, our data related the greatest collagen fibril diameter to the most demanding locomotor modes, conversely, the smallest collagen fibril CSA and the highest tendon CSA were observed in animals showing a hopping locomotion requiring likely little absorption of landing forces given the short jump distances.
Processes and changes experienced by clients during and after naturalistic good-outcome therapies conducted by experienced psychotherapists

Abstract Objective: This study explores processes and changes experienced by clients during and after successful naturalistic therapy conducted by experienced psychotherapists. A taxonomy of content is built and presented, before the prevalence, range, and variation of process— and change categories are explored. Method: Sixteen therapies showing reliable improvement (on OQ-45) at treatment termination and having complete follow-up data up to 3–4 years post therapy were selected for this study. Processes and changes were extracted from clients’ reports of important aspects during therapy and semi-structured interviews from termination and follow-up. A procedure allowing for description, organization, and quantification of this material was developed and followed. Results: The totality of processes and changes (36 categories) reported by clients under and after these therapies are described. The most prevalent of these were exploration and more understanding (from session reports); relational quality and ways of thinking/more understanding (from interviews at termination); therapy process continues and situational changes (from follow-up interviews). Conclusions: Findings suggest that the therapies in this privileged sample are operating through a broad range of processes and changes, with all clients appreciating material from a large share of categories.
Water and nutrients alter herbaceous competitive effects on tree seedlings in a semi‐arid savanna

1 Globally, both climatic patterns and nitrogen deposition rates show directional changes over time. It is uncertain how woody seedlings, which coexist with herbaceous plants in savannas, respond to concurrent changes in water and nutrient availability. 2 We investigated competition effects between herbaceous vegetation and tree seedlings (Colophospermum mopane) under changed water and nutrient (fertilized) conditions in a garden experiment situated in a semi‐arid savanna. 3 Herbaceous competition significantly suppressed woody seedling growth. The effect of herbaceous competition on woody seedling growth remained constant with both increasing water and nutrient availability. However, during a wet‐season drought, herbaceous competition apparently caused premature leaf senescence in non‐irrigated treatments. Fertilization exacerbated negative competition effects during the drought, while irrigation prevented leaf loss of tree seedlings in spite of herbaceous competition and fertilization. 4 Based on a conceptual model, we propose that the vigorous response of herbaceous plants to increased nutrient availability leads to faster depletion of soil water, which increasingly causes water stress in woody seedlings if the interval between watering events is prolonged, e.g. during wet‐season droughts. 5 Synthesis. Our data support the notion that changes in drought frequency are of greater importance to woody recruitment success than changes in annual rainfall amount. Based on the water and nutrient interactions observed in our experiment, we suggest that the effect of increased nitrogen deposition on woody seedling recruitment is contingent on water availability.
Measurement of Void Content and Distribution in Composite Materials through Digital Microscopy

The use of digital optical microscopy techniques to measure the volume fraction and spatial distribution of voids in composite materials manufactured by filament winding is presented and discussed. The volume fraction was measured using the usual technique of object measurement from several individual fields and using mosaic images formed by assembling low magnification fields. The results obtained were consistent showing the usefulness of the mosaic image approach that also provides a global view of the complex microstructure of the material. From the mosaic images contour maps of void number and void area fraction were generated providing a semi-quantitative evaluation of void distribution. Using the tessellation technique for neighborhood analysis the coefficient of variation of the distance between nearest neighboring voids was measured. This parameter allows a quantitative measure of void spatial distribution, revealing homogeneity or clustering of the void population.
Investigation on creep behavior of welded joint of advanced 9%Cr steels

The creep behavior of advanced 9%Cr-1 (BM1) and advanced 9%Cr-2 (BM2) dissimilar welded joints was investigated in this paper, and also the microstructures were elaborately characterized. Based on the fitting with MATLAB, a 3-D curved surface describing the primary and steady-state creep stage was achieved. The comparison of the microstructures of the precreep and aftercreep welded joints shows that δ-ferrite distribution in the heat affected zone (HAZ) of BM2 side plays an important role in determining creep rupture strength. Fracture occurred at the overtempered heat affected zone (OT-HAZ) adjacent to BM2 after creep tests at 538 °C under different stress loads. Microhardness tests revealed that the OT-HAZ adjacent to BM2 has the lowest hardness value compared with the whole welded joint. Numerous creep voids occurring around δ-ferrite, carbides, and grain boundaries were observed on the specimen after creep test. They concentrated and grew up to microcracks, and then induced the fracture at OT-HAZ. Many second phases were also observed in the grain boundary after creep, and the tempered martensite boundaries in the HAZ gradually become obscure as the creep time increases.
Structural Characterization of the Intrinsically Disordered Protein p53 Using Raman Spectroscopy

The intrinsically disordered protein p53 has attracted a strong interest for its important role in genome safeguarding and potential therapeutic applications. However, its disordered character makes difficult a full characterization of p53 structural architecture. A deep knowledge of p53 structural motifs could significantly help the understanding of its functional properties, in connection with its complex binding network. We have applied Raman spectroscopy to investigate the structural composition and the conformational heterogeneity of both full-length p53 and its DNA binding domain (DBD), in different solvent environments. In particular, a careful analysis of the Amide I Raman band, which is highly sensitive to protein secondary structure elements such as α-helices, β-sheets and random coils, has revealed the presence of extended random coils in p53 and predominant β-sheet regions in its DBD. In addition, this analysis has allowed us to explore the ensemble of interchanging conformations in both p53 and its DBD, highlighting a higher conformational heterogeneity in p53 than in its DBD. Furthermore, by applying a principal components analysis, we have identified the principal spectral markers in both p53 and DBD samples. The combination of the two approaches could be insightful for the study of intrinsically disordered proteins, by offering increased versatility and wide application as a label-free, real-time and non-invasive detection method.
Effects of flavonoids on intestinal inflammation, barrier integrity and changes in gut microbiota during diet-induced obesity

Abstract Diet-induced obesity is associated with low-grade inflammation, which, in most cases, leads to the development of metabolic disorders, primarily insulin resistance and type 2 diabetes. Although prior studies have implicated the adipose tissue as being primarily responsible for obesity-associated inflammation, the latest discoveries have correlated impairments in intestinal immune homeostasis and the mucosal barrier with increased activation of the inflammatory pathways and the development of insulin resistance. Therefore, it is essential to define the mechanisms underlying the obesity-associated gut alterations to develop therapies to prevent and treat obesity and its associated diseases. Flavonoids appear to be promising candidates among the natural preventive treatments that have been identified to date. They have been shown to protect against several diseases, including CVD and various cancers. Furthermore, they have clear anti-inflammatory properties, which have primarily been evaluated in non-intestinal models. At present, a growing body of evidence suggests that flavonoids could exert a protective role against obesity-associated pathologies by modulating inflammatory-related cellular events in the intestine and/or the composition of the microbiota populations. The present paper will review the literature to date that has described the protective effects of flavonoids on intestinal inflammation, barrier integrity and gut microbiota in studies conducted using in vivo and in vitro models.
Meaningful weight loss in obese postmenopausal women: a pilot study of high-intensity interval training and wearable technology

Objective: Postmenopausal women cite lack of time as their primary barrier to exercise and related weight control behaviors. The purpose of this study was to address this barrier via testing the feasibility and initial outcomes of a short-duration/high-intensity interval training (HIIT)-based weight loss program among obese postmenopausal women, with descriptive comparison to an endurance-focused exercise program. Methods: A 16-week behavioral program incorporated (1) HIIT to limit time necessary to produce health benefits of exercise, and (2) wearable activity sensors to facilitate self-monitoring exercise. Participants (n = 11; MAge = 59 ± 5.33; MBMI = 32.0 ± 2.53 kg/m2) were randomly assigned to HIIT or endurance exercise. Both groups followed a calorie-restricted diet, attended monthly in-person meetings, weekly weigh-ins and electronic check-ins to review behavioral skills, and monitored their exercise with a Fitbit ChargeHR. Adherence to exercise programs, assessed with the Fitbit sensor, was used to determine feasibility. Results: Participants in the HIIT group (6/6) adhered to their program, whereas 3 of 5 adhered to the Endurance program. Participants in the HIIT group lost twice as much weight as those in the Endurance group (8.7% vs 4.3% of initial body weight), and lost an additional 6 in. of body mass. In addition, only the HIIT group significantly changed fat mass, body mass index, and fat-free mass (Ps < 0.04). Conclusions: These findings support the feasibility and potential effectiveness of HIIT for weight loss and body composition changes in obese postmenopausal women, and indicate that additional investigation of this approach is warranted to reduce postmenopausal chronic disease risk.
Modulation of Donor-Acceptor Distance in a Series of Carbazole Push-Pull Dyes; A Spectroscopic and Computational Study

A series of eight carbazole-cyanoacrylate based donor-acceptor dyes were studied. Within the series the influence of modifying the thiophene bridge, linking donor and acceptor and a change in the nature of the acceptor, from acid to ester, was explored. In this joint experimental and computational study we have used electronic absorbance and emission spectroscopies, Raman spectroscopy and computational modeling (density functional theory). From these studies it was found that extending the bridge length allowed the lowest energy transition to be systematically red shifted by 0.12 eV, allowing for limited tuning of the absorption of dyes using this structural motif. Using the aforementioned techniques we demonstrate that this transition is charge transfer in nature. Furthermore, the extent of charge transfer between donor and acceptor decreases with increasing bridge length and the bridge plays a smaller role in electronically mixing with the acceptor as it is extended.
Tree Diversity Mediates the Distribution of Longhorn Beetles (Coleoptera: Cerambycidae) in a Changing Tropical Landscape (Southern Yunnan, SW China)

Longhorn beetles (Coleoptera : Cerambycidae) have been used to identify sites of high biological diversity and conservation value in cultivated landscapes, but were rarely studied in changing landscapes of humid tropics. This study was conducted in a region of southern Yunnan, China, which was dominated by natural rainforest until 30 years ago, but is successively transformed into commercial rubber monoculture plantations since that time. The objectives were to investigate longhorn beetle species diversity and distribution in the major land use types of this landscape and to estimate the effects of an expected expansion of rubber plantations on the longhorn beetle assemblages. The results showed that tree species diversity (181 species in total) and longhorn beetle diversity (220 species in total) were closely related with no significant differences between the tree and longhorn beetles assemblages shown by similarity distance analysis. There was a highly positive relationship between the estimated species richness of longhorn beetles and the number of tree species. Individual numbers of longhorn beetles and trees were also highly positive related at the sampling sites. Non-metric multidimensional scaling revealed that the degree of canopy coverage, succession age and tree diversity explained 78.5% of the total variation in longhorn beetle assemblage composition. Natural forest sites had significantly higher numbers of species and individuals than any other type of habitat. Although young rubber plantations bear the highest longhorn beetle diversity outside forests (half of the total number of longhorn beetle species recorded in total), they can not provide permanent habitats for most of these species, because they develop into closed canopy plantations with less suitable habitat conditions. Therefore, along with an expected expansion of rubber cultivation which largely proceeds at the expense of forest areas, the habitat conditions for longhorn beetles in this region might decrease dramatically in future.
Simulation of Pinus radiata veneer drying : Moisture content and temperature profiles

A mathematical model for timber drying has been extended to the drying of veneer from which the drying curves, moisture content, and temperature profiles in veneerwood are predicted. The simulation results illustrate that the whole drying process can be divided into three periods: a constant drying-rate period followed by two falling-rate periods. The falling-rate curves could be expressed by two segment lines as a function of veneer average moisture content. Industrial-scale drying tests were performed to verify the model. In the tests, 2.6 mm Pinus radiata veneer sheets both of sapwood and heartwood were dried at dry-bulb temperatures of 155°C to 200°C and wet-bulb temperatures of 65°C to 95°C. The average impinging air velocity in drying was 12.3 m/sec. The close agreement between the measured and the predicted moisture contents after drying gives confidence in applying the model in further work to examine the influence of veneer variables and drying conditions on the drying rate.