bluuebunny/crossref_metadata_2025 huggingface dataset:
In silicodesign of DNA sequences forin vivonucleosome positioning
Authors: Routhier Ethienne , Pierre Edgar , Joubert Alexandra , Lancrey Astrid , Boulé Jean-Baptiste , Mozziconacci Julien
Published: May 2023

The computational design of synthetic DNA sequences with desired in vivo properties is gaining traction in the field of synthetic genomics. We propose here a computational method which combines a kinetic Monte Carlo framework with a deep mutational screening based on deep learning predictions. We apply our method to build regular nucleosome arrays with tailored nucleosomal repeat lengths (NRL) in yeast. Our design is validated in vivo by successfully engineering and integrating thousands of kilobases long tandem arrays of computationally optimized sequences which could accommodate NRLs much larger than the yeast natural NRL. This method delineates the key sequence rules for nucleosome positioning in yeast and is readily applicable to other sequence properties and other genomes.
Microhabitat acclimatization shifts physiological baselines and thermal tolerance of the symbiotic anemone,Anthopleura elegantissima
Authors: Ruggeri Maria , Million Wyatt C , Hamilton Lindsey , Kenkel Carly D
Published: May 2023

Contemporary organisms in extreme environments can give insight into how species will respond to environmental change. The intertidal forms an environmental gradient where stress increases with tidal height. Here, we explore the contribution of fixed genotypic and plastic environmental effects on thermal tolerance of the intertidal anemoneAnthopleura elegantissimaand its algal symbionts using a laboratory-based tank experiment. High intertidal anemones had lower baseline symbiont-to-host cell ratios under control conditions, but their symbionts had higher baseline maximum quantum yield compared to low intertidal anemone symbionts, despite identical symbiont communities. High intertidal anemones maintained greater maximum quantum yield and symbiont-to-host cell ratios under heat stress compared to low intertidal anemones, suggesting that high intertidal holobionts have greater thermal tolerance. However, thermal tolerance of clonal anemones acclimatized to different zones was not explained by tidal height alone, indicating emersion duration is not the sole environmental driver of physiological variation. Fixed genotypic effects also influenced physiological baselines, but did not modulate thermal tolerance, demonstrating thermal tolerance is largely driven by environmental history. These results indicate that this symbiosis is highly plastic and may be able to rapidly acclimatize to climate change, defying the convention that symbiotic organisms are more susceptible to environmental stress.
Cognitively Healthy Centenarians are genetically protected against Alzheimer’s disease specifically in immune and endo-lysosomal systems
Authors: Tesi Niccolo’ , van der Lee Sven , Hulsman Marc , van Schoor Natasja M. , Huisman Martijn , Pijnenburg Yolande , van der Flier Wiesje M. , Reinders Marcel , Holstege Henne
Published: May 2023

BACKGROUND

Alzheimer’s Disease (AD) prevalence increases with age, yet a small fraction of the population reaches ages beyond 100 years without cognitive decline. We aimed to uncover the genetic factors associated with such resilience against AD.

METHODS

Genome-Wide-Association-Studies (GWAS) identified 86 single-nucleotide-polymorphisms (SNPs) associated with AD-risk. We studied each SNP in 2,281 AD-cases, 3,165 middle-aged population controls, and 346 cognitively healthy centenarians, and we combined SNPs into Polygenic Risk Scores (PRS) for each individual. Finally, we investigated the functional properties of the SNPs enriched/depleted in centenarians usingsnpXplorer.

RESULTS

Centenarians were depleted with risk-increasing AD-SNPs and enriched with protective AD-SNPs. The PRS was more than 5-fold lower in centenarians compared to AD cases (p=7.69×10−71) and almost 2-fold lower compared to middle-aged population controls (p=5.83×10−17). The strongest protection was found inANKH, GRN, TMEM106B, SORT1, EPDR1, PLCG2, RIN3, CD2AP, andAPOEassociated alleles. As expected, the genetic protection was diluted in the offspring of the centenarians.

DISCUSSION

Becoming a cognitively healthy centenarian is associated with a complex genetic protection against AD, which concentrates on an advantageous functioning of the endo-lysosomal and immune systems, and their effect on amyloid-clearance.
Insights into human health from phenome- and genome-wide analyses of UK Biobank retinal optical coherence tomography phenotypes
Authors: Zekavat Seyedeh Maryam , Jorshery Saman Doroodgar , Shweikh Yusrah , Horn Katrin , Rauscher Franziska G. , Sekimitsu Sayuri , Kayoma Satoshi , Ye Yixuan , Raghu Vineet , Zhao Hongyu , Ghassemi Marzyeh , Elze Tobias , Segrè Ayellet V. , Wiggs Janey L. , Scholz Markus , Del Priore Lucian , Wang Jay C. , Natarajan Pradeep , Zebardast Nazlee
Published: May 2023

The human retina is a complex multi-layered tissue which offers a unique window into systemic health and disease. Optical coherence tomography (OCT) is widely used in eye care and allows the non-invasive, rapid capture of retinal measurements in exquisite detail. We conducted genome- and phenome-wide analyses of retinal layer thicknesses using macular OCT images from 44,823 UK Biobank participants. We performed phenome-wide association analyses, associating retinal thicknesses with 1,866 incident ICD-based conditions (median 10-year follow-up) and 88 quantitative traits and blood biomarkers. We performed genome-wide association analyses, identifying inherited genetic markers which influence the retina, and replicated our associations among 6,313 individuals from the LIFE-Adult Study. And lastly, we performed comparative association of phenome- and genome-wide associations to identify putative causal links between systemic conditions, retinal layer thicknesses, and ocular disease.

Independent associations with incident mortality were detected for photoreceptor thinning and ganglion cell complex thinning. Significant phenotypic associations were detected between retinal layer thinning and ocular, neuropsychiatric, cardiometabolic and pulmonary conditions. Genome-wide association of retinal layer thicknesses yielded 259 loci. Consistency between epidemiologic and genetic associations suggested putative causal links between thinning of the retinal nerve fiber layer with glaucoma, photoreceptor segment with AMD, as well as poor cardiometabolic and pulmonary function with PS thinning, among other findings.

In conclusion, retinal layer thinning predicts risk of future ocular and systemic disease. Furthermore, systemic cardio-metabolic-pulmonary conditions promote retinal thinning. Retinal imaging biomarkers, integrated into electronic health records, may inform risk prediction and potential therapeutic strategies.

One Sentence Summary

Phenome- and genome-wide associations of retinal OCT images across nearly 50,000 individuals identifies ocular and systemic phenotypes linked to retinal layer thinning, inherited genetic variants linked to retinal layer thickness, and putative causal links between systemic conditions, retinal layer thickness, and ocular disease.
A comparison between a Random Forest model and the Kidney Failure Risk Equation to predict progression to kidney failure
Authors: Wainstein Marina , Rahimi Amir Kamel , Katz Ivor , Healy Helen , Pirabhahar Saiyini , Turner Kylie , Shrapnel Sally
Published: May 2023

Background

Machine learning may offer a superior alternative to traditional prediction tools when used to model complicated, nonlinear interactions between variables. While modern machine learning methods are tagged as “black boxes”, the random forest (RF) classifier can be interrogated to understand the contribution of input variables (feature importance), thereby improving the interpretability of its predictions. We hypothesized that a random forest (RF) classifier would have equivalent, if not superior, performance to the 4-variable Kidney Failure Risk Equation (KFRE) in predicting progression to end stage kidney disease (ESKD) in a chronic kidney disease (CKD) population and explored the impact of serum creatinine and primary renal disease on prediction accuracy.

Methods

A 2-year risk of ESKD was calculated using the 4-variable KFRE and compared to a RF model using the same four variables (age, gender, eGFR and urine albumin creatinine ratio). Four more RF models were developed using a combination of these as well as serum creatinine and primary renal disease. Performance of the KFRE and RF models was assessed by area under a receiver operating (AUC ROC) curve and feature importance was evaluated for each RF model.

Results

Of 1365 patients with CKD from two renal units included in the analysis, 208 progressed to ESKD in the 2-year follow-up period. The AUC ROC for KFRE was 0.95 (95% confidence interval, 0.93 – 0.96) and for the RF model using the same 4 variables 0.97. The remaining four RF models had similar performance (AUC ROC 0.97 – 0.98). In the RF models, eGFR and serum creatinine had the largest effect on risk prediction while gender had the smallest.

Conclusions

Our findings suggest that RF models provide a potential tool to predict CKD progression with competing accuracy and interpretability to the current benchmark equation. They therefore warrant validation in larger and more diverse populations
Prehospital activation of the cardiac catheterisation laboratory in ST-segment elevation myocardial infarction (STEMI) for primary percutaneous coronary intervention (PCI)
Authors: Savage Michael L , Hay Karen , Volbon William , Doan Tan , Murdoch J Dale , Hammett Christopher , Poulter Rohan , Walters Darren L , Denman Russell , Ranasinghe Isuru , Raffel Owen Christopher
Published: May 2023

Background

Prehospital activation of the cardiac catheter laboratory is associated with significant improvements in ST-segment elevation myocardial infarction (STEMI) performance measures. However, there is equivocal data, particularly within Australia regarding its influence on mortality. We assessed the association of prehospital activation on performance measures and mortality in STEMI patients treated with primary percutaneous coronary intervention (PCI) from the Queensland Cardiac Outcomes Registry (QCOR).

Methods

Consecutive ambulance transported STEMI patients treated with primary PCI were analysed from 1stJanuary 2017 to 31stDecember 2020 from the QCOR. The total and direct effects of prehospital activation on the primary outcomes (30-day and 1-year cardiovascular mortality) were estimated using logistic regression analyses. Secondary outcomes were STEMI performance measures.

Results

Among 2498 patients (mean age: 62.2 ± 12.4 years; 79.2% male), 73% underwent prehospital activation. Median door-to-balloon (DTB) time (34mins [26-46] vs 86 mins [68-113]; p<0.001), first-electrocardiograph-to-balloon (ECGTB) time (83.5 mins [72-98] vs 109 mins [81-139]; p<0.001), and proportion of patients meeting STEMI targets (DTB<60mins 90% vs 16%; p<0.001), ECGTB<90mins (62% vs 33%; p<0.001) were significantly improved with prehospital activation. Prehospital activation was associated with significantly lower 30-day (1.6% vs 6.6%; p<0.001) and 1-year cardiovascular mortality (2.9% vs 9.5%; p<0.001). After adjustment, no prehospital activation was strongly associated with increased 30-day (OR: 3.6; 95%CI: 2.2-6.0, p<0.001) and 1-year cardiovascular mortality (OR: 3.0 (95%CI:2.0-4.6; p<0.001).

Conclusions

Prehospital activation of cardiac catheterisation laboratory for primary PCI was associated with significantly shorter time to reperfusion, achievement of STEMI performance measures and lower 30-day and 1-year cardiovascular mortality.

Clinical Perspective

In patients who suffer STEMI, prehospital activation of the cardiac catheter laboratory and initiation of medical therapy is associated with shorter time to reperfusion, greater achievement of performance measures and lower cardiovascular mortality

This study adds to the existing literature and demonstrates that a standardised prehospital activation strategy can be implemented on a large scale

Widespread implementation of standardised prehospital activation strategies may offer opportunity to expedite STEMI care and improve outcomes
Endovascular treatment of ruptured very small intracranial aneurysms: a systematic review and meta-analysis
Authors: Matsukawa Hidetoshi , Elawady Sameh Samir , Sowlat Mohammad Mahdi , Al Kasab Sami , Uchida Kazutaka , Yoshimura Shinichi , Spiotta Alejandro M
Published: May 2023

Background

Endovascular treatment (EVT) is widely accepted for intracranial aneurysms due to its safety and efficacy. However, EVT of ruptured very small intracranial aneurysms (RVSIA) (≤3 mm) is still challenging and the risk-benefit ratio of EVT remains unclear. The aim of this study was to evaluate the safety and efficacy of EVT of RVSIA.

Methods

We performed a systematic review and meta-analysis of the studies on EVT of RVSIA. Pooled prevalence rates were calculated for initial and follow-up complete occlusion rates (Raymond Roy Grade 1), recanalization, retreatment, long-term favorable outcome (modified Rankins scale score 0 to 2 or Glasgow Outcome Scale 4 or 5), procedure-related complications (coil herniation, thromboembolism, and intraprocedural re-rupture), and procedure-related mortality. Pooled odds ratios were calculated to compare these outcomes between simple coiling and stent-assisted coiling (SAC).

Results

Of the 600 studies screened, 24 studies with a total of 1355 RVSIAs treated with EVT were included. The initial and follow-up complete aneurysm occlusion rates were 64% (95% confidence interval [CI]: 52–74%) and 85% (95% CI: 74–92%). The rates of recanalization and retreatment were 6% (95% CI: 3–10%) and 3% (95% CI: 2–4%). The favorable long-term follow-up outcome was observed in 91% (95% CI: 89– 93%) of patients. The rates of coil herniation, thromboembolism, and intraprocedural rupture were 2% (95% CI: 1–8%), 4% (95% CI: 3–6%), and 4% (95% CI: 2–7%), respectively. Mortality was 3% (95% CI: 2–4%). Comparison of outcomes between simple coiling and SAC revealed no significant difference, except for a higher likelihood of recanalization in the coiling group (Odds ratio, 3.51 [95% CI, 1.31–9.45]).

Conclusions

Our meta-analysis demonstrates that EVT for RVSIA is a feasible, effective, and safe approach that is associated with favorable clinical outcomes in both the short and long term.
Prevalence of untreated prediabetes and glucose metabolism disturbances in Mexico: An analysis of nationally representative surveys spanning 2016-2021
Authors: Fermín-Martínez Carlos A. , Paz-Cabrera César Daniel , Basile-Alvarez Martín Roberto , Castro Paulina Sánchez , Núñez-Luna Alejandra , Perezalonso-Espinosa Jerónimo , Ramírez-García Daniel , Antonio-Villa Neftali Eduardo , Vargas-Vázquez Arsenio , Fernández-Chirino Luisa , Carrillo-Herrera Karime Berenice , Cabrera-Quintana Leslie Alitzel , Rojas-Martínez Rosalba , Seiglie Jacqueline A. , Bello-Chavolla Omar Yaxmehen
Published: May 2023

OBJECTIVE

Characterizing prediabetes phenotypes may be useful in guiding diabetes prevention efforts; however, heterogeneous criteria to define prediabetes have led to inconsistent prevalence estimates, particularly in low- and middle-income countries. We estimated trends in untreated prediabetes prevalence in Mexico across different definitions and its association with prevalent cardiometabolic conditions.

METHODS

We conducted a serial cross-sectional analysis of National Health and Nutrition Surveys in Mexico (2016-2021), totaling 21,442 Mexican adults, excluding individuals with diagnosed or undiagnosed diabetes. Prediabetes was defined using ADA (impaired fasting glucose [IFG] 100-125 mg/dL and/or HbA1c 5.7-6.4%), WHO (IFG 110-125 mg/dL), and IEC criteria (HbA1c 6.0-6.4%). Prevalence trends of prediabetes over time were evaluated using Poisson regression and its association with prevalent cardiometabolic conditions with logistic regression.

RESULTS

Prevalence of prediabetes in Mexico in 2021 was 27.3%. Despite an overall downward trend in prediabetes (RR 0.960, 95%CI 0.940-0.979), this decrease was primarily driven by decreases in prediabetes by ADA-IFG (RR 0.883, 95%CI 0.861-0.907) and WHO-IFG criteria (RR 0.878, 95%CI 0.838-0.921), while prediabetes by ADA-HbA1c (RR 1.049, 95%CI 1.022-1.077) and IEC-HbA1C criteria (RR 1.064, 95%CI 1.014-1.115) increased over time. Prediabetes prevalence increased over time in adults >40 years, individuals with central obesity, self-identified as indigenous or living in urban areas. Regardless of the definition, prediabetes was associated with increased risk of cardiometabolic conditions.

CONCLUSIONS

Prediabetes rates in Mexico from 2016-2021 varied based on defining criteria but consistently increased for HbA1c-based definitions and high-risk subgroups. Regardless of the definition, prediabetes clusters subjects with high cardiometabolic risk.
Engineered bacteria titrate hydrogen sulfide and induce concentration-dependent effects on host in a gut microphysiological system
Authors: Hayes Justin A. , Lunger Anna W. , Sharma Aayushi S. , Fernez Matthew T. , Koppes Abigail N. , Koppes Ryan , Woolston Benjamin M.
Published: May 2023

Hydrogen sulfide (H2S) is a gaseous microbial metabolite whose role in gut diseases is debated, largely due to the difficulty in controlling its concentration and the use of non-representative model systems in previous work. Here, we engineeredE. colito titrate H2S controllably across the physiological range in a gut microphysiological system (chip) supportive of the co-culture of microbes and host cells. The chip was designed to maintain H2S gas tension and enable visualization of co-culture in real-time with confocal microscopy. Engineered strains colonized the chip and were metabolically active for two days, during which they produced H2S across a sixteen-fold range and induced changes in host gene expression and metabolism in an H2S concentration-dependent manner. These results validate a novel platform for studying the mechanisms underlying microbe-host interactions, by enabling experiments that are infeasible with current animal andin vitromodels.
Structural insights into human TFIIIC promoter recognition
Authors: Seifert-Davila Wolfram , Girbig Mathias , Hauptmann Luis , Hoffmann Thomas , Eustermann Sebastian , Müller Christoph W.
Published: May 2023

Transcription factor IIIC (TFIIIC) recruits RNA polymerase (Pol) III to most of its target genes. Recognition of intragenic A- and B-box motifs in tRNA genes by TFIIIC modules τA and τB is the first critical step for tRNA synthesis but is mechanistically poorly understood. Here, we report cryo-EM structures of the human 624 kDa TFIIIC complex unbound and bound to a tRNA gene. The τB module recognizes the B-box via DNA shape and sequence readout through the assembly of multiple winged-helix domains. TFIIIC220 forms an integral part of both τA and τB connecting the two subcomplexes via a ∼550 amino acid residue flexible linker. Our data provide a structural mechanism by which high-affinity B-box recognition anchors TFIIIC to promoter DNA and permits scanning for low-affinity A-boxes and TFIIIB for Pol III activation.
Amino acid supplementation confers protection to red blood cells prior to Plasmodium falciparum bystander stress
Authors: Binns Heather Colvin , Alipour Elmira , Nahid Dinah S. , Whitesides John F. , Cox Anderson O’Brien , Furdui Cristina M. , Marrs Glen S. , Kim-Shapiro Daniel B. , Cordy Regina Joice
Published: May 2023

Malaria is a highly oxidative parasitic disease in which anemia is the most common clinical symptom. A major contributor to malarial anemia pathogenesis is the destruction of bystander, uninfected red blood cells. Metabolic fluctuations are known to occur in the plasma of individuals with acute malaria, emphasizing the role of metabolic changes in disease progression and severity. Here, we report that conditioned media fromPlasmodium falciparumculture induces oxidative stress in healthy uninfected RBCs. Additionally, we show the benefit of amino acid pre-exposure for RBCs and how this pre-treatment intrinsically prepares RBCs to mitigate oxidative stress.

Key points

Intracellular ROS is acquired in red blood cells incubated withPlasmodium falciparumconditioned media

Glutamine, cysteine, and glycine amino acid supplementation increased glutathione biosynthesis and reduced ROS levels in stressed RBCs
Structural basis of TFIIIC-dependent RNA Polymerase III transcription initiation
Authors: Talyzina Anna , Han Yan , Banerjee Chiranjib , Fishbain Susan , Reyes Alexis , Vafabakhsh Reza , He Yuan
Published: May 2023

RNA Polymerase III (Pol III) is responsible for transcribing 5S ribosomal RNA (5S rRNA), tRNAs, and other short non-coding RNAs. Its recruitment to the 5S rRNA promoter requires transcription factors TFIIIA, TFIIIC, and TFIIIB. Here we use cryo-electron microscopy to visualize theS. cerevisiaecomplex of TFIIIA and TFIIIC bound to the promoter. Brf1-TBP binding further stabilizes the DNA, resulting in the full-length 5S rRNA gene wrapping around the complex. Our smFRET study reveals that the DNA undergoes both sharp bending and partial dissociation on a slow timescale, consistent with the model predicted from our cryo-EM results. Our findings provide new insights into the mechanism of how the transcription initiation complex assembles on the 5S rRNA promoter, a crucial step in Pol III transcription regulation.
Serine proteinase inhibitors fromNicotiana benthamiana, a non-preferred host plant, inhibit the growth ofMyzus persicae(green peach aphid)
Authors: Feng Honglin , Jander Georg
Published: May 2023

The green peach aphid (Myzus persicae) is a severe agricultural crop pest that has developed resistance to most current control methods, requiring the urgent development of novel strategies. Plant proteinase inhibitors (PINs) are small proteins that protect plants against pathogens and/or herbivores, likely by preventing efficient protein digestion. We identified 67 protease genes in the transcriptomes of threeM. persicaelineages (USDA-Red, G002, and G006). Comparison of gene expression levels in aphid guts and whole aphids showed that several proteases, including a highly expressed serine protease, are significantly overexpressed in the guts. Furthermore, we identified three genes encoding serine protease inhibitors (SerPIN-II1,2, and3) inNicotiana benthamiana, which is a non-preferred host forM. persicae. Using virus-induced gene silencing (VIGS) with a tobacco rattle virus (TRV) vector and overexpression with a turnip mosaic virus (TuMV) vector, we demonstrated thatN. benthamiana SerPIN-II1andSerPIN-II2cause reduced survival and growth, but do not affect aphid protein content. Similarly,SerPIN-II3overexpression reduced survival and growth, andserpin-II3knockout mutations, which we generated using CRISPR/Cas9, increased survival and growth. Whereas protein content was significantly increased in aphids fed onSerPIN-II3overexpressing plants, it was decreased in aphids fed onserpin-II3mutants. Together, our results show that three PIN-IIs fromN. benthamiana, a non-preferred host plant, effectively inhibitM. persicaesurvival and growth, thereby representing a new resource for the development of aphid-resistant crop plants.
Small cationic cysteine-rich defensin-derived antifungal peptide controls white mold in soybean
Authors: Djami-Tchatchou Arnaud Thierry , Tetorya Meenakshi , Codjoe Jennette M. , Shah Dilip M.
Published: May 2023

White mold disease caused by a necrotrophic ascomycete pathogenSclerotinia sclerotiorumresults in serious economic losses of soybean yield in the USA. Lack of effective genetic resistance to this disease in soybean germplasm and increasing pathogen resistance to fungicides makes white mold difficult to manage. Small cysteine-rich antifungal peptides with multi-faceted modes of action hold potential for development as sustainable spray-on bio-fungicides. We have previously reported that GMA4CG_V6 peptide, a 17-amino acid variant of the MtDef4 defensin-derived peptide GMA4CG containing the active γ-core motif, exhibits potent antifungal activity against the gray mold fungal pathogenBotrytis cinerea in vitroandin planta. This peptide exhibited antifungal activity against an aggressive field isolate ofS. sclerotiorum 555 in vitro.It markedly reduced white mold disease symptoms when applied to detached soybean leaves, pods, and stems. Spray-application on soybean plants provided robust control of the white mold disease. GMA4CG_V6 at sub-lethal concentrations reduced sclerotia production. It was also non-phytotoxic to soybean plants. Our results demonstrate that GMA4CG_V6 peptide has high potential for development as a bio-fungicide for white mold control in soybean.
CyuR is a Dual Regulator for L-Cysteine Dependent Antimicrobial Resistance inEscherichia coli
Authors: Rodionova Irina A. , Lim Hyun Gyu , Rodionov Dmitry A , Hutchison Ying , Dalldorf Christopher , Gao Ye , Monk Jonathan , Palsson Bernhard O.
Published: May 2023

Hydrogen sulfide (H2S), mainly produced from L-cysteine (Cys), renders bacteria highly resistant to oxidative stress. This mitigation of oxidative stress was suggested to be an important survival mechanism to achieve antimicrobial resistance (AMR) in many pathogenic bacteria. CyuR (known as DecR or YbaO) is a recently characterized Cys-dependent transcription regulator, responsible for the activation of thecyuAPoperon and generation of hydrogen sulfide from Cys. Despite its potential importance, the regulatory network of CyuR remains poorly understood. In this study, we investigated the roles of the CyuR regulon in a Cys-dependent AMR mechanism inE. colistrains. We found: 1) Cys metabolism has a significant role in AMR and its effect is conserved in manyE. colistrains, including clinical isolates; 2) CyuR negatively controls the expression ofmdlABencoding a transporter that exports antibiotics such as cefazolin and vancomycin; 3) CyuR binds to a DNA sequence motif ‘GAAwAAATTGTxGxxATTTsyCC’ in the absence of Cys, confirmed by anin vitrobinding assay; and 4) CyuR may regulate 25 additional genes as suggested byin silicomotif scanning and transcriptome sequencing. Collectively, our findings expanded the understanding of the biological roles of CyuR relevant to antibiotic resistance associated with Cys.
Pangenome analysis reveals the genetic basis for taxonomic classification of the Lactobacillaceae family
Authors: Rajput Akanksha , Chauhan Siddharth M. , Mohite Omkar S. , Hyun Jason C. , Ardalani Omid , Jahn Leonie J. , Sommer Morten OA , Palsson Bernhard O.
Published: May 2023

Lactobacillaceaerepresent a large family of important microbes that are foundational to the food industry. Many genome sequences ofLactobacillaceaestrains are now available, enabling us to conduct a comprehensive pangenome analysis of this family. We collected 3,591 high-quality genomes from public sources and found that: 1) they contained enough genomes for 26 species to perform a pangenomic analysis, 2) the normalized Heap’s coefficient λ (a measure of pangenome openness) was found to have an average value of 0.27 (ranging from 0.07-0.37), 3) the pangenome openness was correlated with the abundance and genomic location of transposons and mobilomes, 4) the pangenome for each species was divided into core, accessory, and rare genomes, that highlight the species-specific properties (such as motility and restriction-modification systems), 5) the pangenome ofLactiplantibacillus plantarum(which contained the highest number of genomes found amongst the 26 species studied) contained nine distinct phylogroups, and 6) genome mining revealed a richness of detected biosynthetic gene clusters, with functions ranging from antimicrobial and probiotic to food preservation, but ∼93% were of unknown function. This study provides the first in-depth comparative pangenomics analysis of theLactobacillaceaefamily.
A DNA Unwinding Equilibrium Serves as a Checkpoint for CRISPR-Cas12a Target Discrimination
Authors: Singh Jaideep , Liu Kevin G. , Allen Aleique , Jiang Wei , Qin Peter Z.
Published: May 2023

CRISPR-associated proteins such as Cas9 and Cas12a are programable RNA-guided nucleases that have emerged as powerful tools for genome manipulation and molecular diagnostics. However, these enzymes are prone to cleaving off-target sequences that contain mismatches between the RNA guide and DNA protospacer. In comparison to Cas9, Cas12a has demonstrated distinct sensitivity to protospacer-adjacent-motif (PAM) distal mismatches, and the molecular basis of Cas12a’s enhanced target discrimination is of great interest. In this study, we investigated the mechanism of Cas12a target recognition using a combination of site-directed spin labeling, fluorescent spectroscopy, and enzyme kinetics. With a fully matched RNA guide, the data revealed an inherent equilibrium between a DNA unwound state and a DNA-paired duplex-like state. Experiments with off-target RNA guides and pre-nicked DNA substrates identified the PAM-distal DNA unwinding equilibrium as a mismatch sensing checkpoint prior to the first step of DNA cleavage. The data sheds light on the distinct targeting mechanism of Cas12a and may better inform CRISPR based biotechnology developments.
Expression of transcription factors KLF2 and KLF4 is induced by the mammalian Golgi stress response
Authors: Sasaki Kanae , Sakamoto Miyu , Miyake Iona , Tanaka Reishi , Tanaka Ryuya , Tanaka Azusa , Terami Misaki , Komori Ryota , Taniguchi Mai , Wakabayashi Sadao , Sakurai Hajime Tajima , Yoshida Hiderou
Published: May 2023

The Golgi stress response is a homeostatic mechanism that augments Golgi function when Golgi function becomes insufficient (Golgi stress). Glycosylation of the core proteins of proteoglycans is one of the important functions of the Golgi. If the production of core proteins is increased and the amount of glycosylation enzymes for proteoglycans becomes insufficient (PG-type Golgi stress), the proteoglycan pathway of the Golgi stress response is activated, resulting in the transcriptional induction of glycosylation enzymes, including NDST2, HS6ST1 and GLCE. The transcriptional induction of these glycosylation enzymes is regulated by the enhancer element, PGSE-A; however, transcription factors that induce transcription from PGSE-A have not yet been identified. We herein proposed KLF2 and KLF4 as candidate transcription factors for transcriptional induction from PGSE-A, and revealed that their expression was up-regulated in response to PG-type Golgi stress. These results suggest that KLF2 and KLF4 are important regulators of the proteoglycan pathways of the mammalian Golgi stress response.
Brooding and neuroticism are strongly interrelated manifestations of the phenome of depression
Authors: Vasupanrajit Asara , Jirakran Ketsupar , Tunvirachaisakul Chavit , Maes Michael
Published: May 2023

Neuroticism is a subclinical manifestation of the phenome of depression, comprising depressive and anxiety symptoms, and suicidal behaviors. Rumination is positively associated with depression and neuroticism and may mediate the effects of neuroticism on depression. This study aims to determine whether rumination or its components, including brooding or reflection, mediate the effects of neuroticism on depression, or alternatively, whether both neuroticism and rumination are manifestations of the phenome of depression. This study recruited 74 depressed subjects and 44 healthy controls. The depression group was split into groups with high versus low brooding scores. We used partial least squares (PLS) to examine mediation effects. We found that brooding and reflection scores are significantly higher in depressed patients than in controls. Patients with higher brooding scores have increased severity of depression, anxiety, insomnia, neuroticism, and current suicidal ideation as compared with patients with lower brooding scores and controls. There is a strong positive association between rumination, and neuroticism, depression, anxiety, and lifetime and current suicidal behaviors. PLS analysis shows that brooding does not mediate the effects of neuroticism on the depression phenome, because no discriminant validity could be established between neuroticism and brooding, or between neuroticism and brooding and the depression phenome. We were able to extract one validated latent vector from brooding and neuroticism, insomnia, depression, anxiety, and current suicidal behaviors. Overall, this study supports the theory that rumination and neuroticism are manifestations of the phenome of depression, just like affective symptoms, suicidal behaviors, and insomnia.
Moving forward through consensus: a national Delphi approach to determine the top research priorities in prostate cancer in Uganda
Authors: Ssemata Andrew Sentoogo , Muhumuza Richard , Seeley Janet , Lombe Dorothy Chilambe , Mwamba Monde , Msadabwe Susan , Mwaka Amos Deogratius , Aggarwal Ajay
Published: May 2023

Objective

To describe the health system, socioeconomic and clinical factors that influence access to and outcomes of care for prostate cancer (PC) in Uganda.

Design

Qualitative Delphi technique

Setting

Government and private-not-for-profit hospitals

Methods

We applied a two-stage modified Delphi technique to identify the consensus view across cancer experts. In the first round, experts received a questionnaire containing 22 statements drawn from a systematic review of the literature focusing on identifying the reason for the delay in accessing cancer care. Round 2 comprised 18 statements considered the greatest priority from round 1.

Results

We found that the top five research priority areas arise from challenges including: (i) lack of Diagnostic services - Ultrasound, laboratory tests, and biopsy facilities; (ii) High costs of services e.g., surgery, radiotherapy, hormone therapy are unaffordable to most patients, (iii) Lack of critical surgical supplies and essential/critical medicines, (iv) Lack of awareness of cancer as a disease and low recognition of symptoms, (v) Low Healthcare literacy. The lack of critical surgical supplies, high costs of diagnostic investigations and treatments were ranked highest in order of importance in round one. Round two of the survey also revealed lack of diagnostic services, unavailability of critical medicines, lack of radiotherapy options, high costs of treatments and lack of critical surgical supplies as the top priorities.

Conclusion

These research priority areas ought to be addressed in future research to improve prompt prostate cancer diagnosis and care in Uganda. There is need to improve the supply of high-quality affordable anticancer medicines provided timely to prostate cancer patients so as to improve the survivorship from the cancer.

Article Summary

Strengths and limitations of this study

This is a novel Delphi study exploring research priorities for prostate cancer research in Uganda from various stakeholders in cancer care.

The study was informed by a recent systematic review which provided insight into the statements explored in the Delphi technique.

Participants were recruited from various clinical, government aided and private settings and geographical locations giving representativeness of the participants.

A limitation to this study was the low response rates in round 1 and round 2 as most stakeholders were not familiar with the Delphi technique, or how it works.
Overlapping representations of food and social stimuli in VTA dopamine neurons
Authors: Willmore Lindsay , Minerva Adelaide R. , Engelhard Ben , Murugan Malavika , McMannon Brenna , Oak Nirja , Thiberge Stephan Y. , Peña Catherine J. , Witten Ilana B.
Published: May 2023

Dopamine neurons of the ventral tegmental area (VTADA) respond to food and social stimuli and contribute to both forms of motivation. However, it is unclear if the same or different VTADAneurons encode these different stimuli. To address this question, we performed 2-photon calcium imaging in mice presented with food and conspecifics, and found statistically significant overlap in the populations responsive to both stimuli. Both hunger and opposite-sex social experience further increased the proportion of neurons that respond to both stimuli, implying that modifying motivation for one stimulus affects responses to both stimuli. In addition, single-nucleus RNA sequencing revealed significant co-expression of feeding- and social-hormone related genes in individual VTADAneurons. Taken together, our functional and transcriptional data suggest overlapping VTADApopulations underlie food and social motivation.
Improving quartet graph construction for scalable and accurate species tree estimation from gene trees
Authors: Han Yunheng , Molloy Erin K.
Published: May 2023

Summary methods are widely used to estimate species trees from genome-scale data. However, they can fail to produce accurate species trees when the input gene trees are highly discordant because of estimation error and biological processes, such as incomplete lineage sorting. Here, we introduce TREE-QMC, a new summary method that offers accuracy and scalability under these challenging scenarios. TREE-QMC builds upon weighted Quartet Max Cut, which takes weighted quartets as input and then constructs a species tree in a divide-and-conquer fashion, at each step forming a graph and seeking its max cut. The wQMC method has been successfully leveraged in the context of species tree estimation by weighting quartets by their frequencies in the gene trees; we improve upon this approach in two ways. First, we address accuracy by normalizing the quartet weights to account for “artificial taxa” introduced during the divide phase so subproblem solutions can be combined during the conquer phase. Second, we address scalability by introducing an algorithm to construct the graph directly from the gene trees; this gives TREE-QMC a time complexity ofO(n3k), wherenis the number of species andkis the number of gene trees, assuming the subproblem decomposition is perfectly balanced. These contributions enable TREE-QMC to be highly competitive in terms of species tree accuracy and empirical runtime with the leading quartet-based methods, even outperforming them on some model conditions explored in our simulation study. We also present the application of these methods to an avian phylogenomics data set.
Sub-second pair distribution function using a broad bandwidth monochromator
Authors: Magnard Nicolas P. L. , Sørensen Daniel R. , Kantor Innokenty , Jensen Kirsten M. Ø. , Jørgensen Mads R. V.
Published: May 2023

Here the use of a broad energy bandwidth monochromator, i.e. a pair of B4C/W multilayer mirrors (MLMs), is demonstrated for X-ray total scattering (TS) measurements and pair distribution function (PDF) analysis. Data are collected both on powder samples and from metal oxo clusters in aqueous solution at various concentrations. A comparison between the MLM PDFs and those obtained using a standard Si(111) double-crystal monochromator shows that the measurements yield MLM PDFs of high quality which are suitable for structure refinement. Moreover, the effects of time resolution and concentration on the quality of the resulting PDFs of the metal oxo clusters are investigated. PDFs of heptamolybdate clusters and tungsten α-Keggin clusters from X-ray TS data were obtained with a time resolution down to 3 ms and still showed a similar level of Fourier ripples to PDFs obtained from 1 s measurements. This type of measurement could thus open up faster time-resolved TS and PDF studies.
Assessing and predicting the quality of peer reviews: a text mining approach
Authors: Meng Jie
Published: May 2023

Purpose

This paper aims to quantify the quality of peer reviews, evaluate them from different perspectives and develop a model to predict the review quality. In addition, this paper investigates effective features to distinguish the reviews' quality. 

Design/methodology/approach

First, a fine-grained data set including peer review data, citations and review conformity scores was constructed. Second, metrics were proposed to evaluate the quality of peer reviews from three aspects. Third, five categories of features were proposed in terms of reviews, submissions and responses using natural language processing (NLP) techniques. Finally, different machine learning models were applied to predict the review quality, and feature analysis was performed to understand effective features.

Findings

The analysis results revealed that reviewers become more conservative and the review quality becomes worse over time in terms of these indicators. Among the three models, random forest model achieves the best performance on all three tasks. Sentiment polarity, review length, response length and readability are important factors that distinguish peer reviews’ quality, which can help meta-reviewers value more worthy reviews when making final decisions.

Originality/value

This study provides a new perspective for assessing review quality. Another originality of the research lies in the proposal of a novelty task that predict review quality. To address this task, a novel model was proposed which incorporated various of feature sets, thereby deepening the understanding of peer reviews.
A hostile work climate and workplace bullying: reciprocal effects and gender differences
Authors: Rosander Michael , Salin Denise
Published: May 2023

Purpose

In this paper the authors argue that organizational climate and workplace bullying are connected, intertwined and affect each other. More precisely, the focus of the present study is how a hostile climate at work is related to workplace bullying. A hostile work climate is defined as an affective organizational climate permeated by distrust, suspicion and antagonism. The authors tested four hypotheses about the reciprocal effects and possible gender differences.

Design/methodology/approach

The study is based on a longitudinal probability sample of the Swedish workforce (n = 1,095). Controlling for age, the authors used structural equation modelling and cross-lagged structural regression models to assess the reciprocal effects of a hostile work climate on workplace bullying. Gender was added as a moderator to test two of the hypotheses.

Findings

The results showed a strong reciprocal effect, meaning there were significant associations between a hostile work climate and subsequent bullying, β = 0.12, p = 0.007, and between baseline bullying and a subsequent hostile work climate, β = 0.15, p = 0.002. The forward association between a hostile work climate and bullying depended on gender, β = −0.23, p < 0.001.

Originality/value

The findings point to a possible vicious circle where a hostile work climate increases the risk of bullying, which in turn risks creating an even more hostile work climate. Furthermore, the findings point to gender differences in bullying, showing that the effect of a hostile work climate on workplace bullying was stronger for men.
Assessing the transition from mass production to lean manufacturing using a hybrid simulation model of a LEGO® automotive assembly line
Authors: Katsigiannis Michail , Pantelidakis Minas , Mykoniatis Konstantinos
Published: May 2023

Purpose

With hybrid simulation techniques getting popular for systems improvement in multiple fields, this study aims to provide insight on the use of hybrid simulation to assess the effect of lean manufacturing (LM) techniques on manufacturing facilities and the transition of a mass production (MP) facility to incorporating LM techniques.

Design/methodology/approach

In this paper, the authors apply a hybrid simulation approach to improve an educational automotive assembly line and provide guidelines for implementing different LM techniques. Specifically, the authors describe the design, development, verification and validation of a hybrid discrete-event and agent-based simulation model of a LEGO® car assembly line to analyze, improve and assess the system’s performance. The simulation approach examines the base model (MP) and an alternative scenario (just-in-time [JIT] with Heijunka).

Findings

The hybrid simulation approach effectively models the facility. The alternative simulation scenario (implementing JIT and Heijunka LM techniques) improved all examined performance metrics. In more detail, the system’s lead time was reduced by 47.37%, the throughput increased by 5.99% and the work-in-progress for workstations decreased by up to 56.73%.

Originality/value

This novel hybrid simulation approach provides insight and can be potentially extrapolated to model other manufacturing facilities and evaluate transition scenarios from MP to LM.
Organizational maturity models: the leading research fields and opportunities for further studies
Authors: Kucińska-Landwójtowicz Aneta , Czabak-Górska Izabela Dagmara , Domingues Pedro , Sampaio Paulo , Ferradaz de Carvalho Carolina
Published: May 2023

Purpose

The aim of the article is to determine research areas and to recognize the current direction in the development of maturity models, to indicate the key areas of organizational maturity models (OMMs) development and their classification as well as to pinpoint research gaps and areas of potential development of OMMs in the context of scientific research and the needs of management practitioners.

Design/methodology/approach

The research was conducted using the literature review method, bibliometric analysis and visual mappings.

Findings

The empirical classification developed in this paper identified 12 categories based on management areas, constituting the criteria for classifying OMMs models, where OMMs are being developed: Information Technology, Project Management, Business Management and Strategy, Human Resource, Ergonomics, Health and Safety Management, Industry 4.0 concept, Knowledge Management, Process Management, Performance Management, Quality Management, Supply Chain Management, Risk Management and Innovation Management.

Research limitations/implications

The main limitation is the analysis in the scope of topic OMMs including solely the Scopus and Thompson Reuters Web of Science database. Another shortcoming is conducting data analysis and classification based on the abstracts of the selected articles.

Originality/value

This work is a starting point to prospect trends for future revolving around the OMMs crossing different databases.
When does public debt hurt inequality in Africa?
Authors: Andoh Francis Kwaw , Attobrah Emmanuel , Opoku Alexander , Armah Mark Kojo , Dasmani Isaac
Published: May 2023

Purpose

The question of what level of public debt can increase inequality has become crucial in Africa. In this study, the authors examine the effect of public debt on inequality in Africa and estimate the debt-inequality threshold. The authors then examine the moderating role of tax burdens and corruption in the relationship between public debt and inequality.

Design/methodology/approach

Using data from the period 2005 to 2019 in 38 African countries, the generalized method of moment and the dynamic panel threshold regression techniques were employed to achieve the purpose of the study.

Findings

The results reveal that a 1% increase in public debt leads to a rise in inequality by about 0.17%. However, the effects doubles when the public debt ratio hits 57.47%. Tax burden worses the effect of public debt by about 2.9 percentage points, while control of corruption reduces debt effect on inequality by 61 percentage points.

Research limitations/implications

Owing to data availability, the study period was restricted to 2005 to 2019. Moreover, the study could not consider the disagreggation of inequality into different income groups due to pausty of data. While this could narrow the scope of the study, the results provide an important insight for policy makers.

Originality/value

This contributes to the scant literature on the effect of public debt on income inequality in African countries. This study is a novelty because its provides the level of public debt which worsens inequality in Africa, as well as the moderating effects of tax burden and corruption control.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/IJSE-08-2022-0581