bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of inspiratory muscle strength on exercise capacity after lung transplantation
Authors: Sato Tatsuya , Sato Susumu , Oshima Yohei , Yoshioka Yuji , Hamada Ryota , Nankaku Manabu , Ikeda Masaki , Nakajima Daisuke , Chen‐Yoshikawa Toyofumi F. , Date Hiroshi , Matsuda Shuichi , Tabira Kazuyuki 
Published: April 2022

AbstractBackground and PurposeThough inspiratory muscle strength is essential for patients with respiratory disease, it is unclear whether the recovery of inspiratory muscle strength contributes to an exemplary achievement of exercise tolerance after lung transplantation (LTx). We aimed to elucidate the inspiratory muscle strength affects the recovery of exercise capacity after LTx.MethodsRecipients who underwent LTx between June 2017 and September 2018 were enrolled, and 6‐min walking distance (6MWD), quadriceps force, inspiratory muscle strength (maximal inspiratory pressure [MIP]), and spirometry were evaluated at 3, 6, and 12 months after LTx. The relationships between inspiratory muscle strength and changes in physical performance were analyzed.ResultsNineteen recipients (mean age: 44.8 years, male: 32%) who completed all follow‐ups were analyzed. At 3 months after LTx, mean MIP (88.4% predicted) and vital capacity (60.9% predicted), quadriceps force (QF; 2.1 N*m/kg), and 6MWD (504 m) were lower than normal values. After LTx, 6MWD significantly improved up to 12 months. From 3 to 6 months after LTx, changes in MIP were significantly associated with increases in 6MWD by univariate (r = 0.55, p = 0.02) and multivariate (β = 0.59, p = 0.01) regression analyses, whereas changes of QF in place of MIP were significantly associated with the recoveries of 6MWD from 6 to 12 months.DiscussionImprovements in MIP may impact the recovery of exercise capacity in the early phase after LTx. Factors that determine the improvement in exercise capacity following LTx may vary with postoperative time.
Structural insights into DNA binding domain of vancomycin‐resistance‐associated response regulator in complex with its promoter DNA from Staphylococcus aureus
Authors: Kumar Jangam Vikram , Tseng Tien‐Sheng , Lou Yuan‐Chao , Wei Shu‐Yi , Wu Tsung‐Han , Tang Hao‐Cheng , Chiu Yi‐Chih , Hsu Chun‐Hua , Chen Chinpan 
Published: April 2022

AbstractIn Staphylococcus aureus, vancomycin‐resistance‐associated response regulator (VraR) is a part of the VraSR two‐component system, which is responsible for activating a cell wall‐stress stimulon in response to an antibiotic that inhibits cell wall formation. Two VraR‐binding sites have been identified: R1 and R2 in the vraSR operon control region. However, the binding of VraR to a promoter DNA enhancing downstream gene expression remains unclear. VraR contains a conserved N‐terminal receiver domain (VraRN) connected to a C‐terminal DNA binding domain (VraRC) with a flexible linker. Here, we present the crystal structure of VraRC alone and in complex with R1‐DNA in 1.87‐ and 2.0‐Å resolution, respectively. VraRC consisting of four α‐helices forms a dimer when interacting with R1‐DNA. In the VraRC–DNA complex structure, Mg2+ ion is bound to Asp194. Biolayer interferometry experiments revealed that the addition of Mg2+ to VraRC enhanced its DNA binding affinity by eightfold. In addition, interpretation of NMR titrations between VraRC with R1‐ and R2‐DNA revealed the essential residues that might play a crucial role in interacting with DNA of the vraSR operon. The structural information could help in designing and screening potential therapeutics/inhibitors to deal with antibiotic‐resistant S. aureus via targeting VraR.
Desiccation‐tolerance and globular proteins adsorb similar amounts of water
Authors: Brom Julia A. , Pielak Gary J. 
Published: April 2022

AbstractWhen exposed to desiccation stress, extremotolerant organisms from all domains of life produce protective disordered proteins with the potential to inform the design of excipients for formulating biologics and industrial enzymes. However, the mechanism(s) of desiccation protection remain largely unknown. To investigate the role of water sorption in desiccation protection, we use thermogravimetric analysis to study water adsorption by two desiccation‐tolerance proteins, cytosolic abundant heat soluble protein D from tardigrades and late embryogenesis abundant protein 4 from the anhydrobiotic midge Polypedilum vanderplanki, and, as a control, the globular B1 domain of staphylococcal protein G. All samples adsorb similar amounts of water, suggesting that modulated water retention is not responsible for dehydration protection by desiccation‐tolerance proteins.
Structure–function analysis of cysteine residues in the plasmodium falciparum chitinase, PfCHT1
Authors: Kaur Hargobinder , Garber Laine , Murphy James W. , Vinetz Joseph M. 
Published: April 2022

AbstractThe Plasmodium ookinete uses chitinase activity to penetrate the acellular, chitin‐containing peritrophic matrix to invade the mosquito vector. Plasmodium ookinetes from different parasite clades secrete two structurally distinct forms of chitinase, one, a short form lacking a C‐terminal putative chitin‐binding domain (CBD), the other, a long form with both proenzyme and C‐terminal putative chitin‐binding domains. Here, we structurally and functionally characterize the three cysteines in the short chitinase of the human‐infecting malaria parasite, P. falciparum testing the hypothesis that one unpaired cysteine would not contribute to chitinase‐specific enzymatic activity which would identify this residue as potentially involved in intermolecular disulfide bonding and heteromultimeric invasion complex formation as previously described. To test this hypothesis, we produced and characterized recombinant wild‐type and cysteine‐mutation PfCHT1 proteins in E. coli and used biophysical and enzymatic approaches to examine their enzymatic activities and chitin‐binding affinities. The cysteine‐203 PfCHT1 mutation had no effect on chitinolytic and chitin‐binding functions. The cysteine‐220 and cysteine‐230 mutants were enzymatically inactive and did not bind to chitin. The artificial intelligence‐based protein prediction algorithm, AlphaFold, correctly identified the involvement of cys‐220 and cys‐230 in the intramolecular disulfide linkages key to maintaining properly folded chitinase structural integrity. AlphaFold predicted that cys‐203 cysteine is surface exposed and thus involved in intermolecular protein–protein interaction. Production of the cys‐to‐ser 203 PfCHT1 mutant facilitated recombinant protein production. Future cellular and biochemical studies are needed to further understand details of Plasmodium ookinete mosquito midgut invasion.
Characterization of the glutathione‐dependent reduction of the peroxiredoxin 5 homolog PfAOP from Plasmodium falciparum
Authors: Schumann Robin , Lang Lukas , Deponte Marcel 
Published: April 2022

AbstractPeroxiredoxins use a variety of thiols to rapidly reduce hydroperoxides and peroxynitrite. While the oxidation kinetics of peroxiredoxins have been studied in great detail, enzyme‐specific differences regarding peroxiredoxin reduction and the overall rate‐limiting step under physiological conditions often remain to be deciphered. The 1‐Cys peroxiredoxin 5 homolog PfAOP from the malaria parasite Plasmodium falciparum is an established model enzyme for glutathione/glutaredoxin‐dependent peroxiredoxins. Here, we reconstituted the catalytic cycle of PfAOP in vitro and analyzed the reaction between oxidized PfAOP and reduced glutathione (GSH) using molecular docking and stopped‐flow measurements. Molecular docking revealed that oxidized PfAOP has to adopt a locally unfolded conformation to react with GSH. Furthermore, we determined a second‐order rate constant of 6 × 105 M−1 s−1 at 25°C and thermodynamic activation parameters ΔH‡, ΔS‡, and ΔG‡ of 39.8 kJ/mol, −0.8 J/mol, and 40.0 kJ/mol, respectively. The gain‐of‐function mutant PfAOPL109M had almost identical reaction parameters. Taking into account physiological hydroperoxide and GSH concentrations, we suggest (a) that the reaction between oxidized PfAOP and GSH might be even faster than the formation of the sulfenic acid in vivo, and (b) that conformational changes are likely rate limiting for PfAOP catalysis. In summary, we characterized and quantified the reaction between GSH and the model enzyme PfAOP, thus providing detailed insights regarding the reactivity of its sulfenic acid and the versatile chemistry of peroxiredoxins.
Electrostatic fingerprints of catalytically active amino acids in enzymes
Authors: Iyengar Suhasini M. , Barnsley Kelly K. , Xu Rholee , Prystupa Aleksandr , Ondrechen Mary Jo 
Published: April 2022

AbstractThe computed electrostatic and proton transfer properties are studied for 20 enzymes that represent all six major enzyme commission classes and a variety of different folds. The properties of aspartate, glutamate, and lysine residues that have been previously experimentally determined to be catalytically active are reported. The catalytic aspartate and glutamate residues studied here are strongly coupled to at least one other aspartate or glutamate residue and often to multiple other carboxylate residues with intrinsic pKa differences less than 1 pH unit. Sometimes these catalytic acidic residues are also coupled to a histidine residue, such that the intrinsic pKa of the acidic residue is higher than that of the histidine. All catalytic lysine residues studied here are strongly coupled to tyrosine or cysteine residues, wherein the intrinsic pKa of the anion‐forming residue is higher than that of the lysine. Some catalytic lysines are also coupled to other lysines with intrinsic pKa differences within 1 pH unit. Some evidence of the possible types of interactions that facilitate nucleophilicity is discussed. The interactions reported here provide important clues about how side chain functional groups that are weak Brønsted acids or bases for the free amino acid in solution can achieve catalytic potency and become strong acids, bases or nucleophiles in the enzymatic environment.
Structure and DNA binding analysis of AT‐rich interaction domain present in human BAF‐B specific subunit BAF250b
Authors: Giri Malyasree , Gupta Parul , Maulik Aditi , Gracias Magaly , Singh Mahavir 
Published: April 2022

AbstractBAF250b and its paralog BAF250a are the DNA‐binding central hub proteins present in BAF‐B and BAF‐A classes of SWI/SNF chromatin‐remodeling complexes. BAF250b contains an AT‐rich interaction domain (ARID) and C‐terminal BAF250_C domain, and it is found mutated in several cancers. ARID is a conserved helix‐turn‐helix motif‐containing DNA‐binding domain present in several eukaryotic proteins. The ARID of BAF250b has been proposed to play roles in recruiting SWI/SNF to the target gene promoters for their activation. BAF250b ARID structures had been deposited in the protein data bank by a structural genomics consortium. However, it is not well‐studied for its DNA‐binding and solution dynamic properties. Here, we report complete backbone NMR resonance assignments of human BAF250b ARID. NMR chemical shifts and the backbone dynamics showed that the solution structure of the protein matched the reported crystal structures. The structure and chemical shift indexing revealed the presence of a short β‐sheet in the DNA‐binding region of BAF250b ARID that was absent in the structure of its paralog BAF250a ARID. NMR chemical shift perturbations identified DNA‐binding residues and revealed the DNA‐binding interface on BAF250b ARID. NMR data‐driven HADDOCK models of BAF250b ARID – DNA complexes revealed its plausible mode of DNA‐binding. Isothermal titration calorimetry experiments showed that BAF250b ARID interacts with DNA sequences with moderate affinities like BAF250a ARID. However, distinct thermodynamic signatures were observed for binding of BAF250a ARID and BAF250b ARID to AT‐rich DNA sequence, suggesting that subtle sequence and structural differences in these two proteins influence their DNA‐binding.
Evolutionary origin and sequence signatures of the heterodimeric ABCG5/ABCG8 transporter
Authors: Pei Jimin , Cong Qian 
Published: April 2022

AbstractATP‐binding cassette (ABC) systems, characterized by ABC‐type nucleotide‐binding domains (NBDs), play crucial roles in various aspects of human physiology. Human ABCG5 and ABCG8 form a heterodimeric transporter that functions in the efflux of sterols. We used sequence similarity search, multiple sequence alignment, phylogenetic analysis, and structure comparison to study the evolutionary origin and sequence signatures of ABCG5 and ABCG8. Orthologs of ABCG5 and ABCG8, supported by phylogenetic analysis and signature residues, were identified in bilaterian animals, Filasterea, Fungi, and Amoebozoa. Such a phylogenetic distribution suggests that ABCG5 and ABCG8 could have originated in the last common ancestor of Amorphea (the unikonts), the eukaryotic group including Amoebozoa and Opisthokonta. ABCG5 and ABCG8 were missing in genomes of various lineages such as snakes, jawless vertebrates, non‐vertebrate chordates, echinoderms, and basal metazoan groups. Amino‐acid changes in key positions in ABCG8 Walker A motif and/or ABCG5 C‐loop were observed in most tetrapod organisms, likely resulted in the loss of ATPase activity at one nucleotide‐binding site. ABCG5 and ABCG8 in Ecdysozoa (such as insects) exhibit elevated evolutionary rates and accumulate various changes in their NBD functional motifs. Alignment inspection revealed several residue positions that show different amino‐acid usages in ABCG5/ABCG8 compared to other ABCG subfamily proteins. These residues were mapped to the structural cores of transmembrane domains (TMDs), the NBD‐TMD interface, and the interface between TMDs. They serve as sequence signatures to differentiate ABCG5/ABCG8 from other ABCG subfamily proteins, and some of them may contribute to substrate specificity of the ABCG5/ABCG8 transporter.
Effects of X‐ray irradiation on the fitness of the established invasive pest fall armywormSpodoptera frugiperda
Authors: Jiang Shan , He Li‐Mei , He Wei , Zhao Hui‐Yuan , Yang Xian‐Ming , Yang Xue‐Qing , Wu Kong‐Ming 
Published: April 2022

AbstractBACKGROUNDSpodoptera frugiperdahas spread to Africa, Asia, and Oceania, posing a serious threat to global agriculture. We estimated the appropriate dose of X‐ray sterilization forS. frugiperdausing an X‐ray irradiation instrument to investigate environmentally acceptable control techniques, laying the framework for future applications of sterile insect technology (SIT) to manage the pest environmentally‐friendly.RESULTSThis study is the first to investigate the effects of X‐ray irradiation on the growth, development, survival, reproduction, and flight ofS. frugiperda. The results showed that irradiation with 50–400 Gy had no significant effect on pupal eclosion, but females were more sensitive than males in terms of reproductive parameters, especially when doses of radiation were > 350 Gy. After irradiation with a sub‐sterilizing dose of 250 Gy, the parental sterility rate was > 85%, and the sterility traits could be passed on to their offspring, resulting in a continuous decrease in the population of F1and F2generations.CONCLUSIONOur laboratory experiments theoretically confirmed the feasibility of SIT for controllingS. frugiperdain the field using X‐ray radiation. This study provides a theoretical basis for future regional pest management strategies. © 2022 Society of Chemical Industry.
Screening for insecticide resistance in Australian field populations of Bemisia tabaci (Hemiptera: Aleyrodidae) using bioassays and DNA sequencing
Authors: Fang Cao , Hopkinson Jamie E , Balzer Jacob , Frese Michael , Tay Wee Tek , Walsh Thomas 
Published: April 2022

AbstractBackgroundSpecies within the Bemisia tabaci cryptic species complex can cause significant crop damage. We used high‐throughput amplicon sequencing to identify the species composition and resistance allele genotypes in field populations from cotton fields in Australia. For selected populations, the resistance phenotype was determined in bioassays and compared with sequencing data.ResultsA metabarcoding approach was used to analyse the species composition in 144 field populations collected between 2013 and 2021. Two mixed AUS I and MEAM1 populations were detected, whereas the remaining 142 populations consisted of MEAM1 only. High‐throughput sequencing of organophosphate and pyrethroid resistance gene amplicons showed that the organophosphate resistance allele F331W was fixed (> 99%) in all MEAM1 populations, whereas the pyrethroid resistance allele L925I in the voltage‐gated sodium channel gene was detected at varying frequencies [1.0%–7.0% (43 populations); 27.7% and 42.1% (two populations); 95%–97.5% (three populations)]. Neither organophosphate nor pyrethroid resistance alleles were detected in the AUS I populations. Pyrethroid bioassays of 85 MEAM1 field‐derived populations detected no resistance in 51 populations, whereas 32 populations showed low frequency resistance, and 2 populations were highly resistant.ConclusionsWe demonstrate that high‐throughput sequencing and bioassays are complementary approaches. The detection of target site mutations and the phenotypic provides a comprehensive analysis of the low‐level resistance to pyrethroids that is present in Australian cotton farms. By contrast, a limited survey of whitefly populations from horticulture found evidence of high‐level resistance against pyrethroids. Furthermore, we found that the F331W allele (linked to organophosphate resistance) is ubiquitous in Australian MEAM1. © 2022 Commonwealth of Australia. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
TGF‐β receptor mutations and clinical prognosis in Chinese pediatric patients with idiopathic/hereditary pulmonary arterial hypertension
Authors: Zhang Xinyu , Zhang Chen , Li Qiangqiang , Gu Hong 
Published: April 2022

AbstractThe relationship between clinical prognosis and transforming growth factor‐β (TGF‐β) receptor mutations in Chinese pediatric patients with idiopathic/hereditary pulmonary arterial hypertension (IPAH/HPAH) remains unclear. We retrospectively studied the clinical characteristics and outcomes of pediatric patients with IPAH/HPAH who visited our Hospital from September 2008 to December 2020. One hundred and five pediatric patients with IPAH/HPAH were included, 46 of whom carried TGF‐β receptor mutations with a mean age at diagnosis of 82.8 ± 52.7 months, and 67 of them underwent right cardiac catheterization examinations and acute vasodilator testing. The result showed that mutation carriers demonstrated higher pulmonary vascular resistance (p = 0.012), higher right atrial pressure (p = 0.026), and lower cardiac index (p = 0.003). The 1‐, 2‐, and 3‐year survival rates of mutation carriers were 79.4%, 61.5% and 55.6%, respectively, compared with 96.6%, 91.1%, and 85.4% for nonmutation carriers (p = 0.0001). The prognosis of mutation carriers was significantly worse than that of nonmutation carriers. TGF‐β receptor gene mutation is an independent risk factor for death (p = 0.049, odd raito = 3.809, 95% confidence interval 1.006−14.429). In conclusion, TGF‐β receptor mutation is an important genetic factor for the onset of IPAH/PAH in Chinese pediatric patients. Those who carrying TGF‐β receptor mutations have a poor clinical prognosis. Therefore, TGF‐β receptor gene screening for pediatric patients with PAH and more aggressive treatment for mutation carriers are recommended.
Maternal and fetal outcomes of pregnant women with pulmonary arterial hypertension associated with congenital heart disease in Beijing, China: A retrospective study
Authors: Liu Yang , Li Yanna , Zhang Jun , Zhang Dawei , Li Jiachen , Zhao Yichen , Liu Kemin , Ma Xiaolong , Bai Chen , Gu Hong , Fan Xiangming , Wang Jiangang 
Published: April 2022

AbstractAs pulmonary arterial hypertension associated with congenital heart disease (PAH‐CHD) may increase maternal and fetal risk, this study explored the pregnancy outcomes of Chinese women with PAH‐CHD. The clinical data of pregnant women with PAH‐CHD admitted to the Beijing Anzhen Hospital from 2010 to 2019 were retrospectively analyzed; these patients and their offspring were followed up, with a mean period of 5.9 ± 2.7 years. Overall, 260 patients with PAH‐CHD were included. The mean maternal age was 27.7 ± 4.1 years, and 205 (78.8%) patients were nulliparous. The estimated systolic pulmonary artery pressure was 40–50 mmHg in 34.6% of the patients, 50–70 mmHg in 23.1%, and >70 mmHg in 42.3%. More than 96% of patients were diagnosed with PAH‐CHD before pregnancy. During pregnancy, heart failure occurred in 19.2% of the patients. Cesarean delivery was performed in 88.1% (15.0% emergency) of the patients. Complications included fetal distress (5.8%), preterm delivery (34.2%), and low birth weight (33.8%). A total of 15 mothers (5.8%) died, with the highest mortality rate in those with Eisenmenger syndrome (10/43, 23.3%), and 10 offspring died (3.8%), two (0.8%) following hospital discharge and eight (3.1%) while in hospital. Although most pregnant women with PAH‐CHD were able to have children, PAH increased the maternal and fetal risk. Thus, an individualized risk‐based approach with shared decision‐making may be more appropriate in pregnant women with PAH‐CHD.
Right heart thrombi (RHT) and clot in transit with concomitant PE management: Approach and considerations
Authors: Khosla Akhil , Mojibian Hamid , Assi Roland , Tantawy Hossam , Singh Inderjit , Pollak Jeffrey 
Published: April 2022

AbstractRight heart thrombi (RHT) continues to pose a clinical dilemma for multiple specialties and is especially concerning when present with concomitant pulmonary embolism (PE). Patients with PE and RHT are at an increased risk of poor outcomes compared to PE without RHT. Although the exact incidence of RHT is unknown, the increasing use of point‐of‐care ultrasound may lead to an increased detection and frequency of RHT. There are multiple treatment strategies available for RHT, including anticoagulation, systemic thrombolysis, and endovascular and surgical therapies. Given that these treatment strategies involve multiple medical specialties, the management of RHT with concomitant PE can be complex. Currently, there is limited clinical data and guidelines on the treatment and management of RHT. We aim to provide a review on RHT with concomitant PE, including risk stratification, treatment considerations, and our approach to the management of RHT.