bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose Changes for Long-term Opioid Patients Following a State Opioid Prescribing Policy
Authors: Qiu Sijia , Liu Yan , Adetunji Doyinsola O. , Hartzell Sarah , Larson Madalyn , Friedman Sarah
Published: August 2023

Background:

In 2018, Nevada implemented opioid prescribing legislation (AB474) to support the uptake of CDC pain care guidelines. We studied the law’s association with doses over threshold levels of morphine milligram equivalents (MMEs) and with time to dose increases and decreases, among long-term opioid patients.

Methods:

A difference-in-difference study examined dosing changes across opioid prescription episodes (ie, prescriptions within 30 day and within the same dosing threshold). Patients with at least 120 days supply over 6 months in Nevada and Colorado Medicaid pharmacy claims were included. Using a logistic regression model, we compare the predicted probabilities that opioid episodes exceeded 50 MME before and after implementation of the law, in both states. Adjusted hazard ratios (aHR) from a gap time survival model estimated time to escalate above 50 MME among low-dose episodes (<50 MME), and time to de-escalate below 50 MME among high-dose episodes (≥50 MME).

Results:

Among 453,577 episodes (74,292 patients), the Nevada law was associated with a 2.9% reduction in prescriptions over 50 MME (95% CI: −3.5, −2.3) compared with Colorado. While the law was also associated with slower escalation (Nevada: aHR = 0.75; 95% CI: 0.72, 0.77, Colorado: aHR = 1.04; 95% CI: 1.01, 1.06), it was also associated with slower de-escalation (Nevada: aHR = 0.87; 95% CI: 0.84, 0.89, Colorado: aHR = 0.97; 95% CI: 0.96, 0.99).

Conclusions:

Slower dose escalations, rather than faster dose de-escalation, likely explain post-law reductions in doses over 50 MME. Slower dose de-escalations may be due to longer days supply post-policy.
Lack of Follow-Up for Celiac Disease During Childhood Not Associated With Poor Health Outcomes: A Regional Swedish Cohort Study
Authors: Ulnes Maria , Albrektsson Henrik , Størdal Ketil , Saalman Robert , Ludvigsson Jonas F. , Mårild Karl
Published: August 2023

Objectives:

The objective of the study is to examine the association between the lack of follow-up for celiac disease (CD) during childhood and dietary adherence, disease remission, and health-related quality of life (HRQoL).

Methods:

We invited 243 randomly selected children diagnosed with CD in 2013–2018 in Gothenburg, Sweden, and 162 consented to participate (67%). We retrieved information on clinical follow-up and current wellbeing using medical and laboratory records data, as well as validated questionnaires on symptoms of CD, dietary adherence, and HRQoL. We analyzed tissue-transglutaminase antibodies (tTGA) as a measure of disease remission. We defined lack of follow-up as no CD-related physician/dietician-led visit or measurement of tTGA over the past 24 months of study enrollment.

Results:

The mean age at study enrolment was 12.7 (range 7.8–18.2) years. Out of 162 children with an average disease duration of 5.3 (range 2.3–8.8) years, 23 (14%) lacked follow-up. tTGA had normalized in 94% [95% confidence interval (CI) = 71%–100%] of children without follow-up versus 91% (95% CI: 85%–95%) of children with continued follow-up. Of children without follow-up, 65% (95% CI: 38%–86%) reported a dietary adherence score indicating very good adherence, versus 72% (95% CI: 63%–80%) of those with continued follow-up. Also, lack of follow-up was not significantly associated with growth, symptom scores, or HRQoL.

Conclusions:

In this regional cohort study of mostly older children and adolescents, lack of follow-up for CD was not significantly linked to dietary adherence, disease remission, or HRQoL. How these results hold in larger, unselected samples with longer follow-up, including transition to adult care, warrants further study.
Influence of the Number of Revision Surgeries and Nasal Symmetry After Final Rhinoplasty for Patients With Cleft Lip
Authors: Sakamoto Yoshiaki , Miyamoto Junpei , Kishi Kazuo
Published: August 2023

The effects of operative intervention on vertical nasal growth in patients with unilateral cleft lips (CLs) are well described. However, the factors influencing nasal symmetry have not been sufficiently evaluated. Therefore, this study aimed to study the factors that cause difficulties in obtaining nasal symmetry postoperatively in patients with CLs. We conducted a retrospective analysis using data from patients with CLs who underwent a series of treatments at Keio University Hospital from 1990 to 2000. We collected data on the patients’ sex, cleft type, number and time of revision surgery, palatal fistula incidence, and history of the pharyngeal flap and orthognathic surgery. Nasal symmetry was analyzed as the symmetrical ratio after the final touch-up surgery, and multivariate analysis was conducted using binary logistic regression to determine the factors affecting nasal symmetry. This study included 89 patients with unilateral CL. Multivariate analysis revealed that complete cleft lip and palate (P < 0.05, odds ratio = 4.37) and repeated revision surgery (P < 0.05, odds ratio = 9.28) were significant predictors of the final nasal symmetry. Our study showed that cleft type and the number of revision surgeries were identified as important factors for obtaining nasal symmetry after final touch-up rhinoplasty. Revision surgery may be necessary to relieve patients’ psychological stress due to nasal deformity, suggesting that this dilemma needs to be overcome.
Intracranial Solitary Fibrous Tumor Mimicking Meningioma
Authors: Tao Xiaowei , Yan Xuelei , Zhang Yifei , Qin Shiqiang
Published: August 2023

Solitary fibrous tumor (SFT) is a clinically rare tumor derived from mesenchymal spindle cells. Central nervous system SFT represents only 0.09% of tumors occurring on the meninges, while intracranial solitary fibrous tumors (ISFT) are even more rare. Due to the similar genetic characteristics it shares with hemangiopericytoma, in 2016, the World Health Organization (WHO) classified it as a single disease called solitary fibrous tumor (SFT)/hemangiopericytoma. We reported a case of a 60-year-old female with an intracranial solitary fibrous tumor (ISFT). The patient’s magnetic resonance imaging showed a mass adhering extensively to the dura mater, with adjacent thickening of the meninges and evidence of a meningeal tail sign. These radiologic findings suggested a meningioma. The tumor was surgically removed and sent for pathologic examination, which confirmed that the tumor was consistent with a solitary fibrous tumor(WHO III). Due to its rarity and similarities with meningioma, ISFT is often misdiagnosed as other types of brain tumors. ISFT is poorly understood and poses a diagnostic challenge. Our case report presents several features suggestive of meningioma, but histopathological examination after surgery confirmed the diagnosis of SFT. Knowledge of these tumors is crucial for neurosurgeons to include them in preoperative differential diagnosis.
Prediction of Biliary Complications After Human Liver Transplantation Using Hyperspectral Imaging and Convolutional Neural Networks: A Proof-of-concept Study
Authors: Fodor Margot , Zelger Philipp , Pallua Johannes D. , Huck Christian W. , Hofmann Julia , Otarashvili Giorgi , Pühringer Marlene , Zelger Bettina , Hermann Martin , Resch Thomas , Cardini Benno , Oberhuber Rupert , Öfner Dietmar , Sucher Robert , Hautz Theresa , Schneeberger Stefan
Published: August 2023

Background.

Biliary complications (BCs) negatively impact the outcome after liver transplantation. We herein tested whether hyperspectral imaging (HSI) generated data from bile ducts (BD) on reperfusion and machine learning techniques for data readout may serve as a novel approach for predicting BC.

Methods.

Tissue-specific data from 136 HSI liver images were integrated into a convolutional neural network (CNN). Fourteen patients undergoing liver transplantation after normothermic machine preservation served as a validation cohort. Assessment of oxygen saturation, organ hemoglobin, and tissue water levels through HSI was performed after completing the biliary anastomosis. Resected BD segments were analyzed by immunohistochemistry and real-time confocal microscopy.

Results.

Immunohistochemistry and real-time confocal microscopy revealed mild (grade I: 1%–40%) BD damage in 8 patients and moderate (grade II: 40%–80%) injury in 1 patient. Donor and recipient data alone had no predictive capacity toward BC. Deep learning-based analysis of HSI data resulted in >90% accuracy of automated detection of BD. The CNN-based analysis yielded a correct classification in 72% and 69% for BC/no BC. The combination of HSI with donor and recipient factors showed 94% accuracy in predicting BC.

Conclusions.

Deep learning-based modeling using CNN of HSI-based tissue property data represents a noninvasive technique for predicting postoperative BC.
Lateral gating mechanism and plasticity of the BAM complex in micelles andE. coli
Authors: Gopinath Aathira , Rath Tobias , Morgner Nina , Joseph Benesh
Published: August 2023

The β-barrel assembly machinery (BAM) mediates folding and insertion of the majority of OMPs in Gram-negative bacteria. BAM is a penta-heterooligomeric complex consisting of the central β-barrel BamA and four interacting lipoproteins BamB, C, D, and E. The conformational switching of BamA between inward-open (IO) and lateral-open (LO) conformations is required for substrate recognition and folding. However, the mechanism for the lateral gating or how the structural details observedin vitrocorrespond with the cellular environment remains elusive. Here we addressed these questions by characterizing the conformational heterogeneity of BamAB, BamACDE and BamABCDE complexes in detergent micelles and orE. coliusing pulsed dipolar electron spin resonance spectroscopy (PDS). We show that the binding of BamB does not induce any visible changes in BamA and the BamAB complex exists in the IO conformation. The BamCDE complex induces an IO to LO transition through a coordinated movement along the BamA barrel. However, the extracellular loop (L6) is unaffected by the presence of lipoproteins and exhibits a large segmental dynamics extending to the exit pore. PDS experiments with BamABCDE complex in intactE. coliconfirmed the dynamic behavior of both the lateral gate and the L6 in the native environment. Our results demonstrate that the BamCDE complex plays a key role for the function by regulating lateral gating in BamA.
A platform for dissecting force sensitivity and multivalency in actin networks
Authors: Levin Joseph T. , Pan Ariel , Barrett Michael T. , Alushin Gregory M.
Published: August 2023

The physical structure and dynamics of cells are supported by micron-scale actin networks with diverse geometries, protein compositions, and mechanical properties. These networks are composed of actin filaments and numerous actin binding proteins (ABPs), many of which engage multiple filaments simultaneously to crosslink them into specific functional architectures. Mechanical force has been shown to modulate the interactions between several ABPs and individual actin filaments, but it is unclear how this phenomenon contributes to the emergent force-responsive functional dynamics of actin networks. Here, we engineer filament linker complexes and combine them with photo-micropatterning of myosin motor proteins to produce anin vitroreconstitution platform for examining how force impacts the behavior of ABPs within multi-filament assemblies. Our system enables the monitoring of dozens of actin networks with varying architectures simultaneously using total internal reflection fluorescence microscopy, facilitating detailed dissection of the interplay between force-modulated ABP binding and network geometry. We apply our system to study a dimeric form of the critical cell-cell adhesion protein α-catenin, a model force-sensitive ABP. We find that myosin forces increase α-catenin’s engagement of small filament bundles embedded within networks. This activity is absent in a force-sensing deficient mutant, whose binding scales linearly with bundle size in both the presence and absence of force. These data are consistent with filaments in smaller bundles bearing greater per-filament loads that enhance α-catenin binding, a mechanism that could equalize α-catenin’s distribution across actin-myosin networks of varying sizes in cells to regularize their stability and composition.
Virological characteristics of the SARS-CoV-2 XBB.1.5 variant
Authors: Tamura Tomokazu , Irie Takashi , Deguchi Sayaka , Yajima Hisano , Tsuda Masumi , Nasser Hesham , Mizuma Keita , Plianchaisuk Arnon , Suzuki Saori , Uriu Keiya , Begum MST Monira , Shimizu Ryo , Jonathan Michael , Suzuki Rigel , Kondo Takeshi , Ito Hayato , Kamiyama Akifumi , Yoshimatsu Kumiko , Shofa Maya , Hashimoto Rina , Anraku Yuki , Kimura Kanako Terakado , Kita Shunsuke , Sasaki Jiei , Sasaki-Tabata Kaori , Maenaka Katsumi , Nao Naganori , Wang Lei , Oda Yoshitaka ,   The Genotype to Phenotype Japan (G2P-Japan) Consortium, Ikeda Terumasa , Saito Akatsuki , Matsuno Keita , Ito Jumpei , Tanaka Shinya , Sato Kei , Hashiguchi Takao , Takayama Kazuo , Fukuhara Takasuke
Published: August 2023

Circulation of SARS-CoV-2 Omicron XBB has resulted in the emergence of XBB.1.5, a new Variant of Interest. Our phylogenetic analysis suggests that XBB.1.5 evolved from XBB.1 by acquiring the F486P spike (S) mutation, subsequent to the acquisition of a nonsense mutation in ORF8. Neutralization assays showed similar abilities of immune escape between XBB.1.5 and XBB.1. We determined the structural basis for the interaction between human ACE2 and the S protein of XBB.1.5, showing similar overall structures between the S proteins of XBB.1 and XBB.1.5. The intrinsic pathogenicity of XBB.1.5 in hamsters is lower than that of XBB.1. Importantly, we found that the ORF8 nonsense mutation of XBB.1.5 resulted in impairment of MHC expression.In vivoexperiments using recombinant viruses revealed that the XBB.1.5 mutations are involved with reduced virulence of XBB.1.5. Together, these data suggest that the mutations in ORF8 and S could enhance spreading of XBB.1.5 in humans.
Evolution ofE. coliin a mouse model of inflammatory bowel disease leads to a disease-specific bacterial genotype and trade-offs with clinical relevance
Authors: Unni Rahul , Andreani Nadia Andrea , Vallier Marie , Heinzmann Silke S. , Taubenheim Jan , Guggeis Martina A. , Tran Florian , Vogler Olga , Künzel Sven , Hövener Jan-Bernd , Rosenstiel Philip , Kaleta Christoph , Dempfle Astrid , Unterweger Daniel , Baines John F.
Published: August 2023

Inflammatory bowel disease (IBD) is a persistent inflammatory condition that affects the gastrointestinal tract and presents significant challenges in its management and treatment. Despite the knowledge that within-host bacterial evolution occurs in the intestine, the disease has rarely been studied from an evolutionary perspective. In this study, we aimed to investigate the evolution of resident bacteria during intestinal inflammation and whether- and how disease-related bacterial genetic changes may present trade-offs with potential therapeutic importance. Here, we perform anin vivoevolution experiment ofE. coliin a gnotobiotic mouse model of IBD, followed by multiomic analyses to identify disease-specific genetic and phenotypic changes in bacteria that evolved in an inflamed versus a non-inflamed control environment. Our results demonstrate distinct evolutionary changes inE. colispecific to inflammation, including a single nucleotide variant that independently reached high frequency in all inflamed mice. Usingex vivofitness assays, we find that these changes are associated with a higher fitness in an inflamed environment compared to isolates derived from non-inflamed mice. Further, using large-scale phenotypic assays, we show that bacterial adaptation to inflammation results in clinically relevant phenotypes, which intriguingly include collateral sensitivity to antibiotics. Bacterial evolution in an inflamed gut yields specific genetic and phenotypic signatures. These results may serve as a basis for developing novel evolution-informed treatment approaches for patients with intestinal inflammation.
WITHDRAWN: Identification and functional analysis of extrachromosomal circular DNA in plasma extracellular vesicles of liver failure patients
Authors: Xiang Xi , Hong Xiaoning , Yu Yang , Li Jing , Yu Jiaying , Xiao Wenjun , Chen Chen , Huang Defa , Zhong Tianyu , Li Jiang , Qian Yongbing , Li Zhigang
Published: August 2023

Withdrawal statement

The authors have withdrawn their manuscript owing to having identified certain issues with the current representation of the data in the manuscript after performing further analyses of the bioinformatics data from their eccDNA sequencing results. Therefore, the authors do not wish this work to be cited as reference for the project. A revised and corrected version will be submitted in the future. If you have any questions, please contact the corresponding authors.
The non-structural proteins NS3 and NS5A of Hepatitis C Virus (HCV) are degraded by two host proteolysis systems
Authors: Mohamed Sara , Soppa Jörg
Published: August 2023

Each lifecycle of the Hepatitis C virus (HCV) produces structural and non-structural (NS) proteins in equimolar. Structural proteins were either assembled or degraded by host proteolysis systems, while NS proteins remain inside the host cells and don’t accumulate. Therefore, they must be degraded. Here, NS3 and NS5A half-lives were quantified in the presence of autolysosome and proteasome different modulators. Inhibitors of both systems increased the half-life, while inducers decreased the half-life. Furthermore, polyubiquitination of NS3 and NS5A was observed. Additionally, their intracellular co-localization with autolysosome (LAMP2) and proteasome (PSMB5) was observed, and inhibitors of both systems increased the degree of co-localization. A better understanding of NS protein degradation might help to improve medical interventions during HCV infections in the future.
Sox21bunderlies the rapid diversification of a novel male genital structure betweenDrosophilaspecies
Authors: Ridgway Amber M. , Hood Emily , Jimenez Javier Figueras , Nunes Maria D. S. , McGregor Alistair P.
Published: August 2023

The emergence and subsequent diversification of morphological novelties is a major feature of animal evolution1–9. However, in most cases little is known about the molecular basis of the evolution of novel structures and the genetic mechanisms underlying their diversification. The epandrial posterior lobes of the male genital arch is a novelty of some species of theDrosophila melanogastersubgroup10–13. The posterior lobes grasp the ovipositor of the female and then integrate between her abdominal tergites, and therefore these structures are important for copulation and species-recognition10–12,14–17. The posterior lobes evolved from co-option of a Hox regulated gene network from the posterior spiracles10and have since diversified in shape and size in theD. simulansclade in particular over the last 240,000 years driven by sexual selection18–21. The genetic basis of this diversification is highly polygenic but to the best of our knowledge none of the causative genes have yet been identified despite extensive mapping22–30. Identifying the genes underlying the diversification of these secondary sexual structures is essential to understanding the basis of changes in their morphology and the evolutionary impact on copulation and species recognition. Here, we show that the transcription factor encoded bySox21bnegatively regulates posterior lobe size during development. This is consistent with higher and expanded expression ofSox21binD. mauritiana, which develops smaller posterior lobes compared toD. simulans. We tested this by generating reciprocal hemizygotes and confirmed that changes inSox21bunderlie posterior lobe evolution between these two species. Furthermore, we found that differences in posterior lobe size caused by the species-specific allele ofSox21bsignificantly affect the duration of copulation. Taken together, our study reveals the genetic basis for the sexual selection driven diversification of a novel morphological structure and its functional impact on copulatory behaviour.

Highlights

Sox21bregulates the development of the epandrial posterior lobes, a recently evolved novel structure of some species of theDrosophila melanogastersubgroup, which has subsequently rapidly diversified in size and shape.

D. mauritianahas smaller posterior lobes thanD. simulansand more expansive expression ofSox21bin the developing genitalia. Using a reciprocal hemizygosity test, we show that variation inSox21bunderlies the diversification of epandrial posterior lobe size and shape betweenD. simulansandD. mauritiana.

Behavioural tests show that the species allele ofSox21bcauses differences in the duration of copulation in otherwise genetically identical backgrounds.

Sox21bhas evolved betweenD. simulansandD. mauritiana, and contributed to the divergence of a morphological novelty and copulatory behaviour between these two species.
IntracellularPseudomonas aeruginosawithin the airway epithelium of Cystic Fibrosis lung tissues
Authors: Malet Karim , Faure Emmanuel , Adam Damien , Donner Jannik , Liu Lin , Pilon Sarah-Jeanne , Fraser Richard , Jorth Peter , Newman Dianne K. , Brochiero Emmanuelle , Rousseau Simon , Nguyen Dao
Published: August 2023

RATIONALE

Pseudomonas aeruginosa(P.a.) is the major bacterial pathogen colonizing the airways of adult cystic fibrosis (CF) patients and causes chronic infections that persist despite antibiotic therapy. Intracellular bacteria may represent an unrecognized reservoir of bacteria that evades the immune system and antibiotic therapy. While the ability ofP.a. to invade and survive within epithelial cells has been describedin vitroin different epithelial cell models, evidence of this intracellular lifestyle in human lung tissues is currently lacking.

OBJECTIVES

To detect and characterize intracellularP.a. in CF airway epithelium from human lung explant tissues.

METHODS

We sampled the lung explant tissues from CF and non-CF patients undergoing lung transplantation and analyzed lung tissue sections for the presence of intracellularP.a. by quantitative culture and microscopy, in parallel to histopathology and airway morphometry.

MEASUREMENTS AND MAIN RESULTS

P.a. was isolated from the lungs of 7 CF patients undergoing lung transplantation. Microscopic assessment revealed the presence of intracellularP.a. within airway epithelial cells in 3 out of the 7 lungs analyzed, at a varying but rare frequency. We observed those events occurring in lung regions with high bacterial burden.

CONCLUSION

This is the first study describing the presence of intracellularP.a. in CF lung tissues. While intracellularP.a. in airway epithelial cells are likely relatively rare events, our findings highlight the plausible occurrence of this intracellular bacterial reservoir in chronic CF infections.
Structural elucidation of recombinantTrichomonas vaginalis20S proteasome bound to covalent inhibitors
Authors: Silhan Jan , Fajtova Pavla , Bartosova Jitka , Hurysz Brianna M. , Almaliti Jehad , Miyamoto Yukiko , Eckmann Lars , Gerwick William H. , O’Donoghue Anthony J. , Boura Evzen
Published: August 2023

Proteasomes are essential for protein homeostasis in mammalian cells1-4and in protozoan parasites such asTrichomonas vaginalis (Tv).5Tvand other protozoan 20S proteasomes have been validated as druggable targets.6-8However, in the case ofTv20S proteasome (Tv20S), biochemical and structural studies were impeded by low yields and purity of the native proteasome. We successfully made recombinantTv20S by expressing all seven α and seven β subunits together with the Ump-1 chaperone in insect cells. We isolated recombinant proteasome and showed that it was biochemically indistinguishable from the native enzyme. We confirmed that the recombinantTv20S is inhibited by the natural product marizomib (MZB)9and the recently developed peptide inhibitor carmaphycin-17 (CP-17)8,10. Specifically, MZB binds to the β1, β2 and β5 subunits, while CP-17 binds the β2 and β5 subunits. Next, we obtained cryo-EM structures ofTv20S in complex with these covalent inhibitors at 2.8Å resolution. The structures revealed the overall fold of theTv20S and the binding mode of MZB and CP-17. Our work explains the low specificity of MZB and higher specificity of CP-17 towardsTv20S as compared to human proteasome and provides the platform for the development ofTv20S inhibitors for treatment of trichomoniasis.
An effector deletion leads to the breakdown of partial grapevine resistance to downy mildew
Authors: Paineau Manon , Minio Andrea , Mestre Pere , Fabre Frédéric , Mazet Isabelle D. , Couture Carole , Legeai Fabrice , Dumartinet Thomas , Cantu Dario , Delmotte François
Published: August 2023

Grapevine downy mildew, caused by the oomycetePlasmopara viticola, is a globally destructive disease that particularly affect the Eurasian wine grapeV. vinifera. While genetically resistant varieties are becoming more accessible, populations ofP. viticolaare demonstrating rapid adaptability, successfully over-coming these resistances. Here we aimed to identify the avirulence genes involved in the interaction with the Rpv3.1-mediated resistance in grapevine. We sequenced the full genome of 136P. viticolastrains sampled in a natural population of Bordeaux (France) and characterized their development on both resistant and sensitive cultivars. The genome-wide association study allowed the identification of a genomic region associated with the breakdown of Rpv3.1 grapevine resistance (avrRpv3.1 locus). A diploid-aware reassembly of theP. viticolaINRA-Pv221 genome allowed to detect structural variations in this locus, including a major 30 Kbp deletion. At the avrRpv3.1 locus, virulentP. viticolastrains presented deletion on both haplotypes indicating that avirulence is recessive. The deletion involves two closely-related genes that encode proteins containing 800-900 amino acids with a signal peptide. The structure of the predicted proteins contains repeats of the LWY-fold structural modules, typical of oomycete effectors. Moreover, when these proteins were transiently expressed, they induced cell death in grapevines carrying Rpv3.1 resistance, confirming their avirulence nature. The first description of candidate effectors ofP. viticolainvolved in the interaction with resistance gene provides valuable insights into the genetic mechanisms that enableP. viticolato adapt to grapevine resistance, laying a foundation for developing strategies to manage this damaging crop pathogen.
Thermodynamic Coupling of the tandem RRM domains of hnRNP A1 underlie its Pleiotropic RNA Binding Functions
Authors: Levengood Jeffrey D. , Potoyan Davit , Penumutchu Srinivas , Kumar Abhishek , Wang Yiqing , Hansen Alexandar L. , Kutluay Sebla , Roche Julien , Tolbert Blanton S.
Published: August 2023

The functional properties of RNA-binding proteins (RBPs) require allosteric regulation through inter-domain communication. Despite the foundational importance of allostery to biological regulation, almost no studies have been conducted to describe the biophysical nature by which inter-domain communication manifests in RBPs. Here, we show through high-pressure studies with hnRNP A1 that inter-domain communication is vital for the unique stability of its N- terminal domain containing a tandem of RNA Recognition Motifs (RRMs). Despite high sequence similarity and nearly identical tertiary structures, the two RRMs exhibit drastically different stability under pressure. RRM2 unfolds completely under high-pressure as an individual domain, but when appended to RRM1, it remains stable. Variants in which inter-domain communication is disrupted between the tandem RRMs show a large decrease in stability under pressure. Carrying these mutations over to the full-length protein forin vivoexperiments revealed that the mutations affected the ability of the disordered C-terminus to engage in protein-protein interactions and more importantly, they also influenced the RNA binding capacity. Collectively, this work reveals that thermodynamic coupling between the tandem RRMs of hnRNP A1 accounts for its allosteric regulatory functions.
Determinants of Gastrointestinal Group BStreptococcusCarriage in Adults
Authors: Cowley Elise S. , Chaves Ibrahim Zuniga , Osman Fauzia , Suen Garret , Anantharaman Karthik , Hryckowian Andrew J.
Published: August 2023

Background

Streptococcus agalactiae(Group BStreptococcus, GBS) is a commensal Gram-positive bacterium found in the human gastrointestinal and urogenital tracts. Much of what is known about GBS relates to the diseases it causes in pregnant people and neonates. However, GBS is a common cause of disease in the general population with 90% of GBS mortality occurring in non-pregnant people. There are limited data about the predisposing factors for GBS and the reservoirs in the body. To gain an understanding of the determinants of gastrointestinal GBS carriage, we used stool samples and associated metadata to determine the prevalence and abundance of GBS in the gut microbiome of adults and find risk factors for GBS status.

Methods

We used 754 stool samples collected from adults in Wisconsin from 2016-2017 to test for the prevalence and abundance of GBS using a Taqman probe-based qPCR assay targeting two GBS-specific genes:cfpandsip.We compared the microbiome compositions of the stool samples by GBS status using 16S rRNA analysis. We compared associations with GBS status and 557 survey variables collected during sample acquisition (demographics, diet, overall health, and reproductive health) using univariate and multivariate analyses.

Results

We found 137/754 (18%) of participants had detectable GBS in their stool samples with a median abundance of 104 copies per nanogram of starting DNA. There was no difference in GBS status or abundance based on gender. Beta-diversity, Bray-Curtis and Unweighted UniFrac, was significantly different based on carrier status of the participant. Prior to p-value correction, 59/557 (10.6%) survey variables were significantly associated with GBS carrier status and 11/547 (2.0%) variables were significantly associated with abundance (p-value<0.05). After p-value correction, 2/547 (0.4%) variables were associated with GBS abundance: an increased abundance of GBS was associated with a decreased frequency since last dental checkup (p<0.001) and last dental cleaning (p<0.001). Increased GBS abundance was significantly associated with increased frequency of iron consumption (p=0.007) after p-value correction in multivariate models.

Conclusions

GBS is found in stool samples from adults in Wisconsin at similar frequencies as pregnant individuals screened with rectovaginal swabs. We did not find associations between risk factors historically associated with GBS in pregnant people, suggesting that risk factors for GBS carriage in pregnancy may differ from those in the general population. We found that frequency of iron consumption and dental hygiene are risk factors for GBS carriage in Wisconsin adults. Given that these variables were not assayed in previous GBS surveys, it is possible they also influence carriage in pregnant people. Taken together, this work serves as a foundation for future work in developing approaches to decrease GBS abundance in carriers.
Data-Driven Modeling and Analysis of Fatty Acid Desaturase in Plants
Authors: McNaughton Andrew D. , Shanklin John , Raugei Simone , Kumar Neeraj
Published: August 2023

Fatty acids and their derivatives continue to garner attention as sustainable alternatives to petrochemically derived materials. Towards this goal, we examine the plant membrane-bound fatty acid desaturases (FADs) and develop an overview of their 3D structure and phylogenic relationships. Through this effort we developed two plant fatty acid desaturase homology models that we analyzed with substrate docking and molecular dynamics simulations to better understand the diiron binding pocket that is characteristic of these proteins. The comparison between the Omega6 and Delta12 homology models specifically in regards to the binding affinity as a function of carbon chain length indicates that there is a dip in binding affinity near the 18:2 carbon chain length but the rest maintain a rather consistent binding affinity throughout. Furthermore, MD analysis highlights the importance of regions within the cytosolic cap domain on the binding pocket.

PACS:0000, 1111

2000 MSC:0000, 1111

Graphical Abstract

Highlights

Developed pipeline to predict function from protein sequence

Modeled two fatty acid desaturases and predicted their structure and functions

Leveraged docking simulations and molecular dynamics to confirm protein function
Influence of functional and phylogenetic dissimilarity on exotic plant invasion depends on spatial scale
Authors: Perez-Navarro Maria A. , Clark Adam T. , Brian Joshua I. , Shepherd Harry E. R. , Catford Jane A.
Published: August 2023

Darwin’s theory of natural selection provides two seemingly contradictory hypotheses for explaining the success of introduced species: 1) the pre-adaptation hypothesis posits that introduced species that are closely related to native species will be more likely to succeed than distantly related invaders because they already possess relevant characteristics; 2) the limiting-similarity hypothesis posits that invaders that are more similar to resident species will be less likely to succeed due to competitive exclusion. Previous studies assessing this conundrum show mixed results, possibly stemming from variation in study spatial scales and lack of both functional and phylogenetic information.

We used species abundances compiled in a 33-year grassland successional survey based at Cedar Creek Ecosystem Science Reserve (USA) to assess the support for the pre-adaptation and limiting similarity hypotheses at two different spatial scales (neighbourhood scale of 0.5m2, site scale of ~40m2). We combined compositional surveys of 303 vascular plant taxa (256 native, 47 introduced) taken across 2700 plots in a chronosequence of abandonment from agriculture with species functional dissimilarities, phylogenetic distances, environmental covariates and information on species origin.

Our results consistently supported the pre-adaptation hypothesis at the site scale but diverged at neighbourhood scale, with functional dissimilarity supporting the limiting similarity hypothesis and phylogenetic distance supporting the pre-adaptation hypothesis. Introduced species with low leaf dry matter content (LDMC), low height and high seed mass tended to be most abundant than rest of species, while relationships between species abundance and specific leaf area (SLA) varied with scale. Introduced species were more abundant than natives at higher concentrations of soil N but were less abundant than natives over time.

Synthesis:Our study highlights the importance of environmental filtering on grassland community assembly at the scale of a site – here 40 m2, a spatial resolution that is usually considered “local”. This influence of environmental filtering might mask effects of limiting similarity at small “local” scales. Our results demonstrate the importance of accounting for both phylogenetic and functional dissimilarity when examining the complex interaction between species biogeographic origin, functional strategies and evolutionary history as considering one alone can lead to different conclusions.
Use of Chitin:DNA ratio to assess growth form in fungal cells
Authors: Kovács-Simon Andrea , Fones Helen N.
Published: August 2023

Dimorphism, the ability to switch between a ‘yeast-like’ and a hyphal growth form, is an important feature of certain fungi, including important plant and human pathogens. The switch to hyphal growth is often associated with virulence, pathogenicity, biofilm formation and stress resistance. Thus, the ability to accurately and efficiently measure fungal growth form is key to research into these fungi, especially for discovery of potential drug targets. To date, fungal growth form has been assessed microscopically, a process that is both labour intensive and costly. Here, we unite quantification of the chitin in fungal cell walls and the DNA in nuclei to produce a methodology that allows fungal cell shape to be estimated by calculation of the ratio between cell wall quantity and number of nuclei present in a sample of fungus or infected host tissue. Using the wheat pathogenZymoseptoria triticias a test case, with confirmation in the distantly relatedFusarium oxysporum, we demonstrate a close, linear relationship between the chitin:DNA ratio and the average polarity index (length/width) of fungal cells. We show the utility of the method for estimating growth form in infected wheat leaves, differentiating between the timing of germination in two differentZ. triticiisolates using this ratio. We also show that the method is robust to the occurence of thick-walled chlamydospores, which show a chitin:DNA ratio that is distinct from either ‘yeast-like’ blastospores or hyphae.
Identifying and exploring the relationship among the critical success factors of sustainability toward consumer behavior
Authors: Zaman Syed Imran , Kusi-Sarpong Simonov
Published: August 2023

Purpose

The purpose of this study is to find out what is the relationship between sustainability toward consumer behavior. Consumer behavior is the method of choosing, buying and using goods and services with an attachment to needs and wants. Now consumers are aware about sustainability, they make purchase decisions according to environmental safety, benefit to the society and increase economic growth.

Design/methodology/approach

This study validates the result through experts in textile industry by using the Decision-Making Trial and Evaluation Laboratory approach. This method has many benefits which provide decision makers and experts to understand the interdependence and influential relation between the criteria by hierarchical approach.

Findings

According to the results, green culture (F8) and green brand (F3) are the most influential (causal) factors and exert a substantial amount of influence over other factors for achieving organizational performance and sustainability. On the other hand, past experience (F14) and time pressure (F12) are the most influenced (effect) factors that are highly influenced by other factors.

Practical implications

The study conducted in Pakistan underscores the significance of maintaining a healthy and pristine environment for future generations. Both consumers and organizations play a vital role in this endeavor. It is imperative that they actively promote and support goods and services that advocate for sustainability.

Social implications

Mangers should use long-term strategies that meet the high product value to enhance the organization’s reputation, so it will have positive consumer perception. If managers make policies to implement natural resources in their raw material, so this policy avoids conflicts and maintains a balance in our society.

Originality/value

This research delves into the complexities and subtleties associated with the identification and examination of the interconnections between the success factors of sustainability and consumer behavior.
Procurement practices in international development projects: trends, networks and performances
Authors: Bakhshi Javad , Mani Saba , Ahmadi Eftekhari Navid , Martek Igor
Published: August 2023

Purpose

International development projects are a dominant means by which aid is distributed to countries. Over the past 70 years, the distribution of trillions of dollars of development aid has been mediated by the United Nations (UN). However, most of this aid has failed to deliver the expected outcomes for which it was assigned. Nevertheless, a significant proportion of projects can be considered successful. Despite the glaring question as to which factors contribute to the success or failure of projects, no study has comprehensively documented the relationship between procurement mechanisms invoked to deliver aid projects and project outcomes. This study aims to assess this relationship.

Design/methodology/approach

Leveraging network analysis methodology, this study examines the World Bank data set of over 247,000 developmental contracts worldwide granted over the past 20 years. It identifies the range of procurement practices used and interrogates their ability to deliver satisfactory project outcomes.

Findings

Eleven prevalent practices are identified covering aid projects across twelve sectors. As might be expected, Africa is the largest recipient of aid, while the Middle East is the least. Overwhelmingly, international competitive bidding (ICB) is the leading procurement procedure, both in terms of contract number and total dollar value. However, ICB does not always deliver the best outcomes, with other, more boutique approaches sometimes doing better.

Social implications

The breadth of this study, encompassing such a vast data resource, and generating such a rich pool of findings will now empower researchers to take the next important step, which is to progress this study in exploring why it is that certain procurement strategies have worked for some sectors, but not others. Countries, financial institutions, the UN and construction enterprises alike will be very interested in the results.

Originality/value

The spectrum of outcomes identified will be of interest to academics and practitioners alike wishing to investigate further the drivers behind the results described here.
Impact of digital technology usage on firm resilience: a dynamic capability perspective
Authors: Ye Fei , Ke Min , Ouyang You , Li Yina , Li Lixu , Zhan Yuanzhu , Zhang Minhao
Published: August 2023

Purpose

While the usage of digital technology can bring many operational improvements for firms, it is unclear whether it can effectively improve firm resilience to deal with supply chain disruptions caused by emergencies such as COVID-19. From a dynamic capability perspective, this study aims to investigate how digital technology usage can improve firm resilience in a rapidly changing and turbulent environment.

Design/methodology/approach

Based on the survey sample of 237 Chinese firms, the stepwise regression approach was used to examine the proposed research hypotheses.

Findings

The empirical evidence shows that digital technology usage has a U-shaped effect on firm resilience, and that effect is fully achieved by first affecting market acuity and then promoting resource reconfiguration. Moreover, the authors further found that the U-shaped association between digital technology usage and firm resilience is derived from the U-shaped association between digital technology usage and market acuity.

Originality/value

This study enriches the resilience literature by revealing the mechanism of digital technology usage’s effects rather than focusing on the role of specific digital technologies. This study also provides guidance for firms to develop effective digital technology usage strategies.
Employment among older men and women in Vietnam: How their health played a role?
Authors: Giang Long Thanh , Kikkawa Aiko , Park Donghyun , Nguyen Tue Dang
Published: August 2023

Purpose

This study aims to explore the situations and socio-economic and health-related factors associated with employment of older men and women in Vietnam.

Design/methodology/approach

This study used the nationally representative data in 2019 with a sample size of 3,049 older persons (those aged 60 and over). This study applied logistic regression analyses.

Findings

This study found that there were significant differences in employment rates between various groups of older men and women in terms of age group, residential place, marital status and educational level. Controlling for age, education, marital status, place of residence and (in) sufficient income for daily living, the results from logistic models indicated that health issues were strongly associated with lower probability to be employed for both genders. In all tests and regression models, that age and health condition were consistently related with lower employment probability of older persons implied an important consideration in raising normal retirement ages for both men and women.

Research limitations/implications

Due to limitation of the cross-sectional data, this research could not explore how health influences older people’s employment overtime.

Practical implications

Findings of this research provide important and adaptive policy insights for Vietnam to take advantage of older workers for economic growth under an aging population.

Originality/value

To the best of the authors’ knowledge, this has been among the first studies exploring the role of health, which was presented by different indicators, determining employment of older men and women in Vietnam.
Interprofessional obstetric simulation training improves postpartum haemorrhage management and decreases maternal morbidity: a before‐and‐after study
Authors: Lutgendorf Monica A. , Ennen Christopher S. , McGlynn Andrea , Spalding Carmen N. , Deering Shad , Delorey Donald R. , Greer Joy A.
Published: August 2023

Objective

To determine the impact of the Obstetric Simulation Training and Teamwork (OB‐STaT) curriculum on postpartum haemorrhage (PPH) rates and outcomes.

Design

Before‐and‐after study.

Setting

Maternity care hospitals within the USA.

Population

Patients who delivered between February 2018 and November 2019.

Methods

Interprofessional obstetric teamwork training (OB‐STaT) conducted at each hospital. Electronic medical records for deliveries were reviewed for 6 months before and after conducting OB‐STaT at participating hospitals.

Main outcome measures

The PPH rate (blood loss of ≥1000 ml), uterotonic medications used, tranexamic acid use, blood product transfusion, hysterectomy, length of stay and composite maternal morbidity (postpartum haemorrhage, hysterectomy, transfusion of ≥4 units of blood products and intensive care unit admission for PPH).

Results

A total of 9980 deliveries were analysed: 5059 before and 4921 after OB‐STaT. The PPH rates did not change significantly (5.48% before vs 5.14% after, p = 0.46). Composite maternal morbidity decreased significantly by 1.1% (6.35%–5.28%, p = 0.03), massive transfusions decreased by 57% (0.42%–0.18%, p = 0.04) and the mean postpartum length of stay decreased from 2.05 days (1.05 days SD) to 2.01 days (0.91 days SD) (p = 0.04). Following OB‐STaT, haemorrhage medication use increased by 36% (14.8%–51.2%, p = 0.03), the use of tranexamic acid for PPH treatment almost doubled (2.7%–4.8%, p < 0.001) and the rate of hysterectomy significantly increased (0%–0.1%, p = 0.03).

Conclusions

Although the PPH rates did not decrease, OB‐STaT significantly improved maternal morbidity, decreased massive transfusions, and improved PPH management by increasing the utilization of uterotonic medications, tranexamic acid and hysterectomy.