bluuebunny/crossref_metadata_2025_split huggingface dataset:
Over the rainbow: A practical guide for fluorescent protein selection in plant FRET experiments
Authors: Denay Grégoire , Schultz Patrick , Hänsch Sebastian , Weidtkamp‐Peters Stefanie , Simon Rüdiger 
Published: December 2019

AbstractReceptor‐like kinases (RLK) and receptor‐like proteins (RLP) often interact in a combinatorial manner depending on tissue identity, membrane domains, or endo‐ and exogenous cues, and the same RLKs or RLPs can generate different signaling outputs depending on the composition of the receptor complexes they are involved in. Investigation of their interaction partners in a spatial and dynamic way is therefore of prime interest to understand their functions. This is, however, limited by the technical complexity of assessing it in endogenous conditions. A solution to close this gap is to determine protein interaction directly in the relevant tissues at endogenous expression levels using Förster resonance energy transfer (FRET). The ideal fluorophore pair for FRET must, however, fulfil specific requirements: (a) The emission and excitation spectra of the donor and acceptor, respectively, must overlap; (b) they should not interfere with proper folding, activity, or localization of the fusion proteins; (c) they should be sufficiently photostable in plant cells. Furthermore, the donor must yield sufficient photon counts at near‐endogenous protein expression levels. Although many fluorescent proteins were reported to be suitable for FRET experiments, only a handful were already described for applications in plants. Herein, we compare a range of fluorophores, assess their usability to study RLK interactions by FRET‐based fluorescence lifetime imaging (FLIM) and explore their differences in FRET efficiency. Our analysis will help to select the optimal fluorophore pair for diverse FRET applications.
Structure of galactarate dehydratase, a new fold in an enolase involved in bacterial fitness after antibiotic treatment
Authors: Rosas‐Lemus Monica , Minasov George , Shuvalova Ludmilla , Wawrzak Zdzislaw , Kiryukhina Olga , Mih Nathan , Jaroszewski Lukasz , Palsson Bernhard , Godzik Adam , Satchell Karla J. F. 
Published: December 2019

AbstractGalactarate dehydratase (GarD) is the first enzyme in the galactarate/glucarate pathway and catalyzes the dehydration of galactarate to 3‐keto‐5‐dehydroxygalactarate. This protein is known to increase colonization fitness of intestinal pathogens in antibiotic‐treated mice and to promote bacterial survival during stress. The galactarate/glucarate pathway is widespread in bacteria, but not in humans, and thus could be a target to develop new inhibitors for use in combination therapy to combat antibiotic resistance. The structure of almost all the enzymes of the galactarate/glucarate pathway were solved previously, except for GarD, for which only the structure of the N‐terminal domain was determined previously. Herein, we report the first crystal structure of full‐length GarD solved using a seleno‐methoionine derivative revealing a new protein fold. The protein consists of three domains, each presenting a novel twist as compared to their distant homologs. GarD in the crystal structure forms dimers and each monomer consists of three domains. The N‐terminal domain is comprised of a β‐clip fold, connected to the second domain by a long unstructured linker. The second domain serves as a dimerization interface between two monomers. The C‐terminal domain forms an unusual variant of a Rossmann fold with a crossover and is built around a seven‐stranded parallel β‐sheet supported by nine α‐helices. A metal binding site in the C‐terminal domain is occupied by Ca2+. The activity of GarD was corroborated by the production of 5‐keto‐4‐deoxy‐D‐glucarate under reducing conditions and in the presence of iron. Thus, GarD is an unusual enolase with a novel protein fold never previously seen in this class of enzymes.
Type I fatty acid synthase trapped in the octanoyl‐bound state
Authors: Rittner Alexander , Paithankar Karthik S. , Himmler Aaron , Grininger Martin 
Published: December 2019

AbstractDe novo fatty acid biosynthesis in humans is accomplished by a multidomain protein, the Type I fatty acid synthase (FAS). Although ubiquitously expressed in all tissues, fatty acid synthesis is not essential in normal healthy cells due to sufficient supply with fatty acids by the diet. However, FAS is overexpressed in cancer cells and correlates with tumor malignancy, which makes FAS an attractive selective therapeutic target in tumorigenesis. Herein, we present a crystal structure of the condensing part of murine FAS, highly homologous to human FAS, with octanoyl moieties covalently bound to the transferase (MAT—malonyl‐/acetyltransferase) and the condensation (KS—β‐ketoacyl synthase) domain. The MAT domain binds the octanoyl moiety in a novel (unique) conformation, which reflects the pronounced conformational dynamics of the substrate‐binding site responsible for the MAT substrate promiscuity. In contrast, the KS binding pocket just subtly adapts to the octanoyl moiety upon substrate binding. Besides the rigid domain structure, we found a positive cooperative effect in the substrate binding of the KS domain by a comprehensive enzyme kinetic study. These structural and mechanistic findings contribute significantly to our understanding of the mode of action of FAS and may guide future rational inhibitor designs.
Deciphering the mechanistic effects of eIF4E phosphorylation on mRNA‐cap recognition
Authors: Lama Dilraj , Verma Chandra S. 
Published: December 2019

AbstractThe mRNA cap‐binding oncoprotein “eIF4E” is phosphorylated at residue S209 by Mnk kinases, and is closely associated with tumor development and progression. Despite being well‐established, mechanistic details at the molecular level of mRNA recognition by eIF4E due to phosphorylation have not been clearly elucidated. We investigated this through molecular modeling and simulations of the S209 phosphorylated derivative of eIF4E and explored the associated implication on the binding of the different variants of mRNA‐cap analogs. A key feature that emerges as a result of eIF4E phosphorylation is a salt‐bridge network between the phosphorylated S209 (pS209) and a specific pair of lysine residues (K159 and K162) within the cap‐binding interface on eIF4E. This interaction linkage stabilizes the otherwise dynamic C‐terminal region of the protein, resulting in the attenuation of the overall plasticity and accessibility of the binding pocket. The pS209‐K159 salt‐bridge also results in an energetically less favorable environment for the bound mRNA‐cap primarily due to electrostatic repulsion between the negative potentials from the phosphates in the cap and those appearing as a result of phosphorylation of S209. These observations collectively imply that the binding of the mRNA‐cap will be adversely affected in the phosphorylated derivative of eIF4E. We propose a mechanistic model highlighting the role of eIF4E phosphorylation as a regulatory tool in modulating eIF4E: mRNA‐cap recognition and its potential impact on translation initiation.
Therapeutic efficacy of hepatitis B virus vaccine in treatment of chronic HBV infections: A systematic review and meta‐analysis
Authors: Ghozy Sherief , Nam Nguyen Hai , Radwan Ibrahim , Karimzadeh Sedighe , Tieu Thuan Minh , Hashan Mohammad Rashidul , Abbas Alzhraa Salah , Eid Peter Samuel , Vuong Nguyen Lam , Khang Nguyen Vinh , Elgabalawy Eman , Sayed Ahmed Kamal , Hoa Pham Thi Le , Huy Nguyen Tien 
Published: December 2019

SummaryThere is a need for improved treatment of patients with chronic hepatitis B (CHB). We reviewed the literature to explore the efficacy of HB vaccines alone or in combination therapy (CT) with antiviral drugs in CHB patients and to meta‐analyze data from randomized controlled trials. We conducted a systematic search in ten databases. All studies investigating the efficacy of HBV vaccine in HBV infected patients were included with no restrictions. Among 1359 studies initially identified, 23 studies (n = 1956 patients) were included for the final analysis. CT showed a significant reduction of HBV DNA compared with analogue monotherapy (AM) at the 12‐month follow‐up period (odds ratio (OR) = 2.835, 95% confidence interval (CI) [1.275, 6.306], p = .011). Additionally, CT also remarkably induce HbsAg loss in comparison with AM (OR = 11.736, 95% CI [1.841, 74.794], p = .009). Our pooled data revealed no difference between treatment and control regarding alanine aminotransferase normalization, HBeAg seroconversion, and HBeAg disappearance. In addition, CT using vaccine and NAs resulted in a statistically significant higher incidence of adverse effects than AM. The therapeutic effects of combination therapy for patients with CHB were encouraging, but future studies need to investigate all possible treatment combinations and assess their cost‐effectiveness.
Anti‐windup design of active disturbance rejection control for sampled systems with input delay
Authors: Geng Xinpeng , Liu Tao , Hao Shoulin , Zhong Chongquan , Wang Qing‐Guo 
Published: December 2019

SummaryA novel anti‐windup design of active disturbance rejection control (ADRC) is proposed for industrial sampled systems with input delay and saturation. By using a generalized predictor to estimate the delay‐free system output, a modified extended state observer is designed to simultaneously estimate the system state and disturbance, which could become an anti‐windup compensator when the input saturation occurs. Accordingly, a feedback controller is analytically designed for disturbance rejection. By proposing the desired closed‐loop transfer function for the set‐point tracking, a prefilter is designed to tune the tracking performance while guaranteeing no steady‐state output tracking error. A sufficient condition for the closed‐loop system stability is established with proof for practical application subject to the input delay variation. Illustrative examples from the literature are used to demonstrate the effectiveness and merit of the proposed control design.
Experimental and modeling study on the progressive collapse resistance of a reinforced concrete frame structure under a middle column removal scenario
Authors: Zhang Qiang , Li Yaozhuang 
Published: December 2019

SummaryA reinforced concrete (RC) frame structure is one of the widely used structural system. A localized damage caused by extreme events may lead to progressive collapse of entire structures. In this paper, progressive collapse test of three 1/3‐scaled reinforced concrete frame, including a single‐story without a slab, single‐story with a slab, and double‐story with slabs, are reported. Experimental results show that the progressive collapse process of RC frame consisted of five stages: an elastic stage, yield stage, beam mechanism stage, transient stage and catenary stage. The reinforced concrete slabs contribute to large progressive collapse resistance force compared with the specimen without slab. Furthermore, validation of the test results by using a refined solid finite element model was established. The effect of extensive parameters, including slab thickness, beam section height, seismic design intensity, and so forth, on the progressive collapse performance of RC frame structures was simulated as well. The simulation results indicated that the collapse resistance of RC structures was substantially improved with the increased of the slab thickness and seismic design intensity. Finally, a simplified model is proposed in accordance with experimental and numerical results to calculate the collapse resistance of RC frame structures.
Probabilistic risk assessment on wind turbine towers subjected to cyclone‐induced wind loads
Authors: Jaimes Miguel A. , García‐Soto A. David , Martín del Campo J. Osvaldo , Pozos‐Estrada Adrián 
Published: December 2019

AbstractA probabilistic risk assessment to estimate the economic impact on wind turbine towers subjected to cyclone‐induced wind loads is applied. An event‐based probabilistic framework is used to assess the risk parameters for selected hazard events. The results are integrated considering all uncertainties related to each part of the process in a probabilistic formal way. The hazard is defined by a set of nonoverlapping stochastic events that exhaust the considered sample space, including the spatial distribution, the annual frequency, and the randomness of the hazard intensity. The vulnerability is defined in terms of the first and second statistical moments: the expected damage and its corresponding variance (or standard deviation) for a certain type of wind turbine towers. The vulnerability component of the model is an important contribution of the study; it uses a realistic modeling of the wind field, and instead of one (as in other studies), three failure modes are considered to characterize the vulnerability. The risk is expressed in economic terms, namely, the single‐event expected loss, the average annual loss, the pure premium, and the loss exceedance curve. The approach is applied to a probabilistic tropical cyclone wind risk assessment on 3001 wind turbine towers from 65 wind farms in Mexico. It is concluded that the selected metrics are of especial importance for risk retention (financing), particularly if schemes or risk transfer instruments are to be defined, and therefore, they will be a very valuable contribution to further studies in defining strategies for financial protection of national infrastructure against wind disasters induced by cyclones.
Investigating the role of organic carbon amendments and microbial denitrification gene abundance in nitrogen removal from experimental agricultural drainage ditches with low‐grade weirs
Authors: Faust Derek R. , Kröger Robert , Baker Beth H. , Brooks John P. , Cox Michael S. , Rush Scott A. 
Published: December 2019

AbstractLow‐grade weirs placed within agricultural drainage ditches in the Lower Mississippi Alluvial Valley can be used as a management practice to enhance nitrogen removal. The addition of organic carbon amendments within ditches that contain weirs could further increase nitrogen removal. Through repeated trials, changes in ‐N concentration between inflow and outflow were variable in the ditch without weirs, while only decreases in concentration were observed in ditches with weirs. Significant differences in ‐N concentrations were observed between treatments, with greater removal of ‐N observed in dissolved organic carbon treatments compared to control and particulate organic carbon treatments. At medium‐ and high‐flow rates, respectively, dissolved organic carbon treatments resulted in greater ‐N concentration decreases of 31.6% and 27.1% compared to 19% and 11.6% in particulate organic carbon treatments and 18.6% and 17.2% in control treatments. Significant effects of weirs and sampling date on nirS, nirK, nosZ, and 16S rRNA gene abundances were observed. Observed increases in ‐N removal with organic carbon amendments, provides support for continued investigation on improving the efficacy of organic carbon amendments as a best management practice for ‐N removal in agricultural drainage ditches.Practitioner points

Dissolved organic carbon amendments increased nitrate–nitrogen removal.

Only decreases in nitrate–nitrogen concentration were observed in ditches with weirs.

Increasing flow rate did not affect nitrate–nitrogen removal.

Abundance of denitrification‐performing microbes likely did not affect N removal.

Lack of anaerobic soil conditions and short residence time reduced nitrate‐N removal.
Allostasis and the origins of adult-onset diabetes
Authors: Leslie R. David , Vartak Tanwi 
Published: December 2019

AbstractPhysiological plasticity enables homeostasis to be maintained in biological systems, but when such allostasis fails, then disease can develop. In a new population-based study by Rolandsson et al (10.1007/s00125-019-05016-3), autoimmunity, defined by an immunogenotype, predicted adult-onset non-insulin requiring diabetes. Type 1 diabetes is no longer viewed as a disease confined to children, with a significant proportion, maybe the majority, presenting in adulthood. Such cases masquerade as type 2 diabetes and their identification has clinical utility. Nevertheless, in this study, autoimmunity had a limited effect on the overall risk of adults developing diabetes.
Cross-Sectional Associations Between Dietary Antioxidant Vitamins C, E and Carotenoid Intakes and Sarcopenic Indices in Women Aged 18–79 Years
Authors: Welch A. A. , Jennings A. , Kelaiditi E. , Skinner J. , Steves C. J. 
Published: December 2019

AbstractThe prevalence of sarcopenia is increasing in aging populations, so prevention is critical. Vitamins (A, C, E and carotenoids) modify skeletal muscle via protein and collagen synthesis and anti-inflammatory activities. Previous studies have not investigated intake of these vitamins in relation to sarcopenic indices in both younger and older-aged women. Indices of skeletal muscle mass (as fat-free mass (FFM) relative to body size) were measured using DXA and leg explosive power (LEP) using the Nottingham Power Rig in 2570 women aged 18–79 years. Adjusted measures of skeletal muscle were calculated according to quintiles of vitamin C, E, retinol and carotenoid intake, derived from Food Frequency Questionnaires, after stratification by age. Higher vitamin C intake was associated with significantly higher indices of FFM and LEP, (Q5-Q1 = 2.0–12.8%, P < 0.01–0.02). Intakes of total and individual carotenoids were significantly associated with indices of FFM and LEP (Q5-Q1 = 1.0–7.5%). Vitamin E was significantly associated with FFM% and FFMBMI only. In mutually adjusted analysis with vitamin C, total carotene, vitamin E and protein in the model, the strongest associations were with vitamin C. These associations were stronger in younger women (< 65 years). For the first time, our research shows higher dietary intakes of antioxidant vitamins, particularly vitamin C, is associated with higher skeletal muscle mass and power in free-living women. These findings have relevance for the treatment and prevention of frailty and sarcopenia throughout adulthood.
Structural and molecular characteristics of axons in the long head of the biceps tendon
Authors: Blumer Roland , Boesmueller Sandra , Gesslbauer Bernhard , Hirtler Lena , Bormann Daniel , Pastor Angel M. , Streicher Johannes , Mittermayr Rainer 
Published: December 2019

AbstractThe innervation of the long head of the biceps tendon (LHBT) is not sufficiently documented. This is a drawback since pathologies of the LHBT are a major source of shoulder pain. Thus, the study aimed to characterize structurally and molecularly nervous elements of the LHBT. The proximal part of 11 LHBTs was harvested intraoperatively. There were 8 female and 3 male specimens. Age ranged from 66 to 86 years. For structural analyses, nervous elements were viewed in the transmission electron microscope. For molecular characterization, we used general neuronal markers including antibodies against neurofilament and protein gene product 9.5 (PGP9.5) as well as specific neuronal markers including antibodies against myelin basic protein (MBP), calcitonin gene-related product (CGRP), substance P (SP), tyrosine hydroxylase (TH), and growth-associated protein 43 (GAP43). Anti-neurofilament and anti-PGP9.5 visualized the overall innervation. Anti-MBP visualized myelination, anti-CGRP and anti-SP nociceptive fibers, anti-TH sympathetic nerve fibers, and anti-GAP43 nerve fibers during development and regeneration. Immunolabeled sections were analyzed in the confocal laser scanning microscope. We show that the LHBT contains unmyelinated as well as myelinated nerve fibers which group in nerve fascicles and follow blood vessels. Manny myelinated and unmyelinated axons exhibit molecular features of nociceptive nerve fibers. Another subpopulation of unmyelinated axons exhibits molecular characteristics of sympathetic nerve fibers. Unmyelinated sympathetic fibers and unmyelinated nociceptive fibers express proteins that are found during development and regeneration. Present findings support the hypothesis that ingrowth of nociceptive fibers are the source of chronic tendon pain.
Extensometer forensics: what can the data really tell us?
Authors: Burbey Thomas J. 
Published: December 2019

AbstractExtensometer data have an advantage over satellite-based data for monitoring land subsidence in that extensometer data provide continuous measurements (hourly or better temporal resolution) at very high precision (several tens of microns) over a known depth interval; the latter is important for isolating groundwater pumping from other causes of land subsidence attributed to tectonics or eustatic adjustments in the Earth’s crust. This investigation aims to identify a semi-analytical procedure for quantifying aquifer and aquitard properties from a single extensometer record in lieu of the time-consuming development of more complex numerical models to quantify and constrain these parameter values. In spite of a limited 12-year record and the fact that water levels both decline and increase on an annual basis, this study successfully and reasonably estimated both aquifer and aquitard parameters at the Lorenzi extensometer site in Las Vegas Valley, Nevada (USA), when compared to the estimates developed numerically. The key factors that allow for estimates of elastic and inelastic skeletal-specific storage and hydraulic conductivity of the aquitards and elastic specific storage and hydraulic conductivity of the intervening aquifers is the presence of pumping cycles at multiple frequencies, and measured heads at all the aquifer units covered in the extensometer record. There is an inherent assumption that the aquitards possess the same hydrologic characteristics and are homogeneous and isotropic. This assumption is also a usual limitation in numerical modeling of these settings because of the complex temporal head relationships occurring within the aquitards that are rarely, if ever, measured.