bluuebunny/crossref_metadata_2025 huggingface dataset:
High-resolution analysis of individual
Drosophila melanogaster
larvae uncovers individual variability in locomotion and its neurogenetic modulation
Authors: Thane Michael , Paisios Emmanouil , Stöter Torsten , Krüger Anna-Rosa , Gläß Sebastian , Dahse Anne-Kristin , Scholz Nicole , Gerber Bertram , Lehmann Dirk J. , Schleyer Michael
Published: April 2023

Neuronally orchestrated muscular movement and locomotion are defining faculties of multicellular animals. Due to its simple brain and genetic accessibility, the larva of the fruit fly
Drosophila melanogaster
allows one to study these processes at tractable levels of complexity. However, although the faculty of locomotion clearly pertains to the individual, most studies of locomotion in larvae use measurements aggregated across animals, or animals tested one by one, an extravagance for larger-scale analyses. This prevents grasping the inter- and intra-individual variability in locomotion and its neurogenetic determinants. Here, we present the IMBA (individual maggot behaviour analyser) for analysing the behaviour of individual larvae within groups, reliably resolving individual identity across collisions. We use the IMBA to systematically describe the inter- and intra-individual variability in locomotion of wild-type animals, and how the variability is reduced by associative learning. We then report a novel locomotion phenotype of an adhesion GPCR mutant. We further investigated the modulation of locomotion across repeated activations of dopamine neurons in individual animals, and the transient backward locomotion induced by brief optogenetic activation of the brain-descending ‘mooncrawler’ neurons. In summary, the IMBA is an easy-to-use toolbox allowing an unprecedentedly rich view of the behaviour and its variability of individual larvae, with utility in multiple biomedical research contexts.
Distance doesn't matter: migration strategy in a seabird has no effect on survival or reproduction
Authors: Kentie Rosemarie , Morgan Brown J. , Camphuysen Kees C. J. , Shamoun-Baranes Judy
Published: April 2023

Migrating animals show remarkable diversity in migration strategies, even between individuals from the same population. Migrating longer distances is usually expected to be costlier in terms of time, energy expenditure and risks with potential repercussions for subsequent stages within the annual cycle. Such costs are expected to be balanced by increased survival, for example due to higher quality wintering areas or lower energy expenditure at lower latitudes. We compared reproductive parameters and apparent survival of lesser black-backed gulls (
Larus fuscus
) breeding in The Netherlands, whose winter range extends from the UK to West Africa, resulting in one-way migration distances that differ by more than 4500 km. Individuals migrating furthest arrived later in the colony than shorter distance migrants, but still laid in synchrony with the colony and consequently had a shorter pre-laying period. This shorter pre-laying period affected neither egg volumes nor hatching success. We found no relationship between migration distance and apparent survival probability, corresponding with previous research showing that annual energy expenditure and distance travelled throughout the year is similar across migration strategies. Combined, our results indicate an equal fitness payoff across migration strategies, suggesting there is no strong selective pressure acting on migration strategy within this population.
Three-dimensional morphology of the biramous appendages in
Isoxys
from the early Cambrian of South China, and its implications for early euarthropod evolution
Authors: Zhang Caixia , Liu Yu , Ortega-Hernández Javier , Wolfe Joanna M. , Jin Changfei , Mai Huijuan , Hou Xianguang , Guo Jin , Zhai Dayou
Published: April 2023

Early euarthropod evolution involved a major transition from lobopodian-like taxa to organisms featuring a segmented, well-sclerotized trunk (arthrodization) and limbs (arthropodization). However, the precise origin of a completely arthrodized trunk and arthropodized ventral biramous appendages remain controversial, as well as the early onset of anterior–posterior limb differentiation in stem-group euarthropods. New fossil material and micro-computed tomography inform the detailed morphology of the arthropodized biramous appendages in the carapace-bearing euarthropod
Isoxys curvirostratus
from the early Cambrian Chengjiang biota. In addition to well-developed grasping frontal appendages,
I. curvirostratus
possesses two batches of morphologically and functionally distinct biramous limbs. The first batch consists of four pairs of short cephalic appendages with robust endites with a feeding function, whereas the second batch has more elongate trunk appendages for locomotion. Critically, our new material shows that the trunk of
I. curvirostratus
was not arthrodized. The results of our phylogenetic analyses recover isoxyids as some of the earliest branching sclerotized euarthropods, and strengthens the hypothesis that arthropodized biramous appendages evolved before full body arthrodization.
Nicotine inhibits lycopene cyclase in Sphingomonas paucimobilis strain B-54, but not in Sphingomonas echinoides strain B-3126
Authors: Viswanathan Vandana , Siddaramappa Shivakumara
Published: April 2023

Lycopene cyclase-mediated conversion of the non-cyclic lycopene to the bicyclic β-carotene is a crucial step in the carotenogenesis pathway of bacteria, including those of Sphingomonas spp. Nicotine is a potent inhibitor of this enzyme (CrtY), but the molecular mechanism of its action remains to be elucidated. Some Sphingomonas spp. are known to be capable of degrading nicotine, but its effect on carotenoid biosynthesis in these bacteria has not been reported. In this study, the ability of nicotine to inhibit CrtY in Sphingomonas paucimobilis strain B-54 and Sphingomonas echinoides strain B-3126 was investigated, and it was found that cyclic carotenoids were produced in the latter strain even in the presence of the alkaloid. Therefore, it is likely that the CrtY of strain B-3126 escapes the inhibitory effect of nicotine. Further studies using mutation, complementation, and structural characterization are required to understand the differential effects of nicotine in strains B-54 and B-3126.
GASTRIC ACIDITY IN DIFFERENT PHENOTYPES OF SYMPTOMATIC GASTROESOPHAGEAL REFLUX DISEASE
Authors: Gardner Jerry D.
Published: April 2023

Background

The present report examines gastric pH from normal subjects and different gastroesophageal reflux disease (GERD) phenotypes to compare the distributions of gastric pH values and of changes in gastric acid concentrations to those reported previously for esophageal pH from the same groups of subjects. I also examined total esophageal acidity as a function of total gastric acidity in the different groups of subjects.

Methods

I analyzed 24-hour gastric and esophageal pH recordings from normal subjects and subjects with a particular GERD phenotype to calculate total integrated acidity and total time pH<4. I also examined gastric pH recordings for the distributions of gastric pH values and the distributions of changes in gastric acidity.

Results

There were different distributions for gastric pH, but virtually identical distributions of changes in gastric acid concentrations in the different groups of subjects. There was a significant positive relationship between total integrated esophageal acidity and total integrated gastric acidity in different GERD phenotypes, but not in normal subjects. The slope of the line relating integrated esophageal acidity to gastric acidity correlated directly with the responses of different GERD phenotypes to PPI treatment reported previously by others.

Conclusions

It seems possible esophageal acidity and gastric acidity can influence each other and by so doing account for the variation in the differences in the distributions of values of pH and acid concentrations among normal subjects and different GERD phenotypes. Furthermore, the strength of the relationship between esophageal and gastric acidity can determine the response to PPI treatment.
Geographical variation in treated psychotic and other mental disorders in Finland by region and urbanicity
Authors: Suokas Kimmo , Kurkela Olli , Nevalainen Jaakko , Suvisaari Jaana , Hakulinen Christian , Kampman Olli , Pirkola Sami
Published: April 2023

Background

In Finland, prevalence of schizophrenia is higher in the eastern and northern regions and co-occurs with the distribution of schizophrenia polygenic risk scores. Both genetic and environmental factors have been hypothesized to contribute to this variation, but its reasons are not fully understood. We aimed to examine the prevalence of psychotic and other mental disorders by region and degree of urbanicity, and the impacts of socio-economic adjustments on these associations.

Methods

Nationwide population registers from 2011 to 2017 and healthcare registers from 1975 to 2017. We used 19 administrative and three aggregate regions, and a seven-level urban-rural classification with 250 × 250 m resolution. Prevalence ratios (PRs) were calculated by Poisson regression models and adjusted for gender, age, and calendar year (basic adjustments), and origin, residential history, urbanicity, household income, economic activity, and physical comorbidity (additional adjustments) on an individual level. Average marginal effects were used to visualize interaction effects between region and urbanicity.

Results

A total of 5 898 180 individuals were observed. All mental disorders were slightly more prevalent (PR 1.03 [95% CI, 1.02-1.03]), and psychotic disorders (1.11 [1.10-1.12]) and schizophrenia (1.19 [1.17-1.21]) considerably more prevalent in eastern and northern than in western coastal regions. After the additional adjustments, however, the PRs were 0.95 (0.95-0.96), 1.00 (0.99-1.01), and 1.03 (1.02-1.04), respectively. Urban residence was associated with increased prevalence of psychotic disorders across all regions (adjusted PR 1.21 [1.20-1.22]).

Conclusions

Socioeconomic and sociodemographic factors modulate the within-country geographical distribution of mental disorders highlighting their truly contextual nature.
Non-Metastatic Axillary Lymph Nodes Have Distinct Morphology and Immunophenotype in Obese Breast Cancer patients at Risk for Metastasis
Authors: Song Qingyuan , Muller Kristen E. , Hondelink Liesbeth M. , diFlorio-Alexander Roberta M. , Karagas Margaret , Hassanpour Saeed
Published: April 2023

Obese patients have worse breast cancer outcomes than normal weight women including a 50% to 80% increased rate of axillary nodal metastasis. Recent studies have shown a potential link between increased lymph node adipose tissue and breast cancer nodal metastasis. Further investigation into potential mechanisms underlying this link may reveal potential prognostic utility of fat-enlarged lymph nodes in breast cancer patients. In this study, a deep learning framework was developed to identify morphological differences of non-metastatic axillary nodes between node-positive and node-negative obese breast cancer patients. Pathology review of the model-selected patches found an increase in the average size of adipocytes (p-value=0.004), an increased amount of white space between lymphocytes (p-value<0.0001), and an increased amount of red blood cells (p-value<0.001) in non-metastatic lymph nodes of node-positive breast cancer patients. Our downstream immunohistology (IHC) analysis showed a decrease of CD3 expression and increase of leptin expression in fat-replaced axillary lymph nodes in obese node-positive patients. In summary, our findings suggest a novel direction to further investigate the crosstalk between lymph node adiposity, lymphatic dysfunction, and breast cancer nodal metastases.
Risk factors for food contamination among children 6-59 months discharged from community management of acute malnutrition (CMAM) programmes for severe acute malnutrition (SAM) in Aweil East, South Sudan
Authors: Wells Joseph , Abugo David Gama , Angong John , Lamwaka Nancy Grace , Gallandat Karin , Hassan Jackson Lwate , Deng Lino , Save Dimple , Braun Laura , Gose Mesfin , Amanya Jacob , Ayoub Khamisa , King Sarah , Stobaugh Heather , Cumming Oliver , D’Mello-Guyett Lauren
Published: April 2023

Children under-five years of age are particularly vulnerable to severe acute malnutrition (SAM), and the risk factors associated with relapse to SAM are poorly understood. Possible causes are asymptomatic or symptomatic infection with enteric pathogens, with contaminated food as a critical transmission route. This cross-sectional study comprised a household survey with samples of child food (n=382) and structured observations of food preparation (n=197) among children aged 6-59 months that were discharged from treatment in community management of acute malnutrition (CMAM) programmes in Aweil East, South Sudan. We quantifiedEscherichia coliand total faecal coliforms (TFCs), measured in colony forming units per g of food (CFU/g), as indicators of microbial contamination of child food. A modified hazard analysis critical control point (HACCP) approach was utilised to determine critical control points (CCPs) followed by multivariate logistic regression analysis to understand the risk factors associated with contamination. Over 40% of samples were contaminated withE. coli(43% >0E. coliCFU/g, 95%CI 38-48%), and 90% had >10 TFCs (CFU/g) (>10TFC CFU/g, 95%CI 87-93%). Risk factors associated (p<0.05) with child food contamination included if the child fed themselves (95% CI 1.16, 3.44, log[odds] = 2.20), exposure to animals (95% CI 0.28, 1.68, log[odds] = 0.97), and protective factors for contamination included feeding with a spoon (95% CI -7.81, -1.54, log[odds] = -4.17). This study highlights strategies that can support interventions that reduce food contamination exposure in young children and help further protect those that are highly vulnerable to recurrent exposure to diarrhoeagenic pathogens.
Factors Associated with Arteriovenous Fistula Maturation Failure among Patients Undergoing Hemodialysis in Hospitals Based in a Low and Middle-Income Country
Authors: Sichona Arlon S , Kyaruzi Victor Meza , Joseph Alex , Mavura Maurice P , Khamis Ramadhani H
Published: April 2023

Introduction

The demand for haemodialysis among patients with end stage renal disease (ESRD) is rising worldwide, arteriovenous fistulas (AVF) are considered the gold standard vascular access modality for hemodialysis (HD) because of its longer patency, enhanced durability, and reduced risk of infection for those that mature compared to grafts and central venous catheters. This study will therefore assess the factors associated with arteriovenous fistula maturation for patients requiring hemodialysis in Dar es Salaam.

Methods

A multi-centre based prospective study conducted among patients with ESRD between April 2021 to May 2022 at Muhimbili National Hospital (MNH), Jakaya Kikwete Cardiac Institute (JKCI), Comprehensive Community Based Rehabilitation in Tanzania (CCBRT),Kairuki hospital (KH) in Dar es Salaam. Patients with End stage renal disease eligible for arteriovenous fistula (AVF) creation and Hemodialysis were included. Socio-demographic data were extracted from the patients, intraoperative and postoperative variables were obtained from medical records. Patients were assessed through eight weeks for maturation and complications. Data analyzed accordingly by IBM-SPSS version 27.0, Univariate and multivariate analysis were used to stratify the factors and control the confounders for the effects on outcome, and p-value of <5% was used to state the level of significance at 95% CI.

Results

Total of 151 fistulas were created, most (80.8%) were created on male, (31.8%) in the age group of less than 50 Years old, 58.9% of the participants had normal Body Mass Index (BMI), with majority (45%) being suffered from Hypertension and 54% of them were using Antihypertensive medication. Brachial cephalic fistulas were the most common type of fistula created 77(51%) and most matured 67(52.7%) among ESRD patients who had AVF creation, while radial cephalic fistulas were the most failed created AVFs 13 (54%). The AVF maturation failure rate was 16%.

Conculusion

Failure of newly created AVF is a major barrier to the successful establishment of hemodialysis access, in this study the failure rate of AVF maturation was 16 percent. The major factors associated with failure to mature were; extreme age group (50-59), being suffered with both hypertension and diabetes, long period of alcohol taking and distal location of AVF(radiocephalic fistula).Vascular imaging was not regularly done to assess the status of veins and arteries for AVF creation.
Structural complexity of brain regions in mild cognitive impairment and Alzheimer’s disease
Authors: Tibon Roni , Madan Christopher R. , Vaghari Delshad , Reyes-Aldasoro Constantino Carlos
Published: April 2023

Early detection of Alzheimer’s disease (AD) has been a major focus of current research efforts to guide interventions at the earliest stages of the disease. Subtle changes to the brain might be observed with neuroimaging techniques, even before symptoms surface. We interrogated brain images obtained with Magnetic Resonance Imaging (MRI) from two large-scale dementia datasets (namely, ADNI and BioFIND) to establish the utility of fractal dimensionality (FD)—a relatively understudied measure that estimates the complexity of 3D structures (in this case, brain regions)—for the detection of AD. We show that FD can be used to detect group differences between patients and healthy controls, with the former showing significantly reduced complexity across multiple brain regions. Furthermore, these measures were successful when used as features for individual-based classification and were highly consistent across the two datasets. Finally, the contribution of specific brain regions to individual-based classification adhered to previous literature on the properties of the brain’s memory network. Taken together, the study offers novel and interpretable evidence for the utility of FD for the detection of AD.
Longitudinal alterations in brain microstructure surrounding subcortical ischemic stroke lesions detected by free-water imaging
Authors: Nägele Felix L. , Petersen Marvin , Mayer Carola , Bönstrup Marlene , Schulz Robert , Gerloff Christian , Thomalla Götz , Bastian Cheng
Published: April 2023

Background

Free-water imaging identifies subtle changes in white matter microstructure indicative of cellular and extracellular pathologies not visible on conventional stroke MRI. We explore the spatial extent and temporal trajectory of free-water changes in patients with subcortical stroke and their relationship to symptoms, as well as lesion evolution.

Methods

Twenty-seven patients with isolated subcortical infarct with mean age of 66.73 (SD 11.57) and median initial NIHSS score of 4 (IQR 4) received MRI 3-5 days, 1 month, 3 months and 12 months after symptom-onset. After lesion segmentation, 8 unique tissue shells (2 mm distance) surrounding stroke lesions were created. Extracellular freewater and fractional anisotropy of the tissue (FAT), derived from diffusion-weighted MRI, were averaged within tissue shells/stroke lesions, and normalized to corresponding contralateral regions. Linear mixed-effects models and t-tests were used for statistics. Baseline imaging measures were correlated with clinical outcomes 3 months after stroke.

Results

We found increased free-water and decreased FATin the stroke lesion, as well as the surrounding tissue with a characteristic spatio-temporal distribution. Free-water and FATchanges were most prominent within the lesion and gradually became less with increasing distance from the lesion. Free-water elevations continuously increased over time and peaked after 12 months. In contrast, FATdecreases were most pronounced 1 month after stroke, after which there was a steady increase leading to similarly reduced FATlevels 12 months compared to 3-5 days after stroke. Higher perilesional free-water and higher lesional FATat baseline were correlated with greater reductions in lesion size, while there were no associations with clinical measures.

Conclusions

Both free-water and FATare altered beyond isolated subcortical stroke lesions. The spatial extent of these extracellular and cellular changes varies differentially over time indicating a dynamic parenchymal response to the initial insult characterized by vasogenic edema, cellular damage and white matter atrophy.
IDENTIFYING DIFFERENT PHENOTYPES OF SYMPTOMATIC GASTROESOPHAGEAL REFLUX DISEASE USING ARTIFICIAL INTELLIGENCE
Authors: Gardner Jerry D. , Triadafilopoulos George
Published: April 2023

Introduction

The Lyon Consensus Conference proposed criteria for the clinical diagnosis of three different phenotypes of gastroesophageal reflux disease: nonerosive gastroesophageal reflux disease, Reflux Hypersensitivity, and Functional Heartburn.

Methods

In the present study, we examined the potential of ChatGPT, an artificial intelligence-based conversational large language model to describe how one can identify the different phenotypes as identified by the Lyon Consensus Conference, and to provide a diagnosis when given important clinical findings in a given patient with a particular phenotype.

Results

Although in our analyses ChatGPT captured correct information regarding symptoms, upper gastrointestinal endoscopy findings and response to gastric antisecretory agents when asked to describe different phenotypes, it failed, however, to return correct information on esophageal acid exposure time and the association of symptoms with esophageal reflux episodes. ChatGPT was even less effective in returning the correct diagnosis after being given specific clinical features of a particular phenotype.

Conclusions

Although it seems likely that the ability of ChatGPT to capture information from multiple sources will improve with future use and refinement, presently it is inadequate as a standalone tool for processing information for the description or diagnosis of different clinical disease states. On the other hand, artificial intelligence might prove useful to clinicians in performing tasks that involve obtaining data from a single source such as the electronic medical record and generating a document having a standardized format such as a discharge summary.
Ongoing symptoms and functional impairment 12 weeks after testing positive to SARS-CoV-2 or influenza in Australia: an observational cohort study
Authors: Brown Matthew , Gerrard John , McKinlay Lynne , Marquess John , Sparrow Teneika , Andrews Ross
Published: April 2023

Objective

In a highly vaccinated Australian population we aimed to compare ongoing symptoms and functional impairment 12 weeks after PCR-confirmed COVID-19 infection with PCR-confirmed influenza infection.

Methods and Analysis

The study commenced upon a positive PCR test for either COVID-19 or influenza in June 2022 during concurrent waves of both viruses. Participants were followed up 12 weeks later in September 2022 and self-reported ongoing symptoms and functional impairment. We conducted a multivariate logistic regression analysis, controlling for age, sex, First Nations status, vaccination status, and socio-economic profile.

Results

There were 2 195 and 951 participants in the COVID-19 and influenza-positive cohorts respectively. After controlling for potential predictor variables, we found no evidence to suggest adults with COVID-19 were more likely to have ongoing symptoms (21.4% vs 23.0%, aOR 1.18; 95% CI 0.92-1.50) or moderate to severe functional impairment (4.1% vs 4.4%, OR 0.81; 95% CI 0.55-1.20) at 12 weeks after their diagnosis than adults who had influenza.

Conclusions

In a highly vaccinated population exposed to the SARS-CoV-2 omicron variant, long COVID may manifest as a post-viral syndrome of no greater severity than seasonal influenza but differing in terms of the volume of people affected and the potential impact on health systems. This study underscores the importance of long COVID research featuring an appropriate comparator group.

What is already known on this subject?

Post-acute infection syndromes are associated with a range of illnesses, including COVID-19 and influenza. “Long COVID” may pose a risk to health systems.

What are the new findings?

In a highly vaccinated population whose primary exposure has been to the Omicron variant, the rates of ongoing symptoms and moderate to severe functional impairment at 12 weeks after COVID-19 are no different to influenza.

How might these results change the focus of research or clinical practice?

The public health impact arising from long COVID may not stem from severity, but from volume. We do not dismiss the validity of long COVID but recommend an appropriate comparator group when researching this condition.
An unsupervised deep clustering for Bone x-ray classification and anomaly detection
Authors: Zhou Guola , Hu Caiping , Zhang Yulin , Jiang Jieru
Published: April 2023

In the medical field, bone abnormality detection is a very important issue. Bone abnormalities include various diseases such as fractures, osteoporosis, bone tumors, and joint diseases. If these diseases are not diagnosed and treated in a timely manner, they can seriously affect the health and quality of life of patients. Artificial intelligence has made remarkable advances in Cluster analysis of medical big data, effectively mining its hidden associations to provide effective information for clinical diagnosis and medical research. However, the effectiveness of deep learning in domains with limited or no labeled data is often limited. To address this issue, we propose a novel and reliable two-stage unsupervised deep clustering framework for skeletal anomaly detection. This framework combines neural network parameters with feature clustering for collaborative learning to detect anomalies. We trained eight separate models, one for classification and seven for anomaly detection, using the MURA dataset, the largest publicly available skeletal imaging dataset. In the first stage, our approach achieved an average sensitivity and specificity of 99.76% and 99.53%, respectively. The second stage performed optimally with an average sensitivity and specificity of 83.28% and 97.56%, respectively. Our method can be easily implemented as software modules and used as a visualization tool for skeletal physicians, making it a promising approach for future development.
Reproducibility of 3D MRSI for imaging human brain glucose metabolism using direct (2H) and indirect (1H) detection of deuterium labeled compounds at 7T and clinical 3T
Authors: Niess Fabian , Strasser Bernhard , Hingerl Lukas , Niess Eva , Motyka Stanislav , Hangel Gilbert , Krššák Martin , Gruber Stephan , Spurny-Dworak Benjamin , Trattnig Siegfried , Scherer Thomas , Lanzenberger Rupert , Bogner Wolfgang
Published: April 2023

Introduction

Deuterium metabolic imaging (DMI) and quantitative exchange label turnover (QELT) are novel MR spectroscopy techniques for non-invasive imaging of human brain glucose and neurotransmitter metabolism with high clinical potential. Following oral or intravenous administration of non-ionizing [6,6’-2H2]-glucose, its uptake and synthesis of downstream metabolites can be mapped via direct or indirect detection of deuterium resonances using2H MRSI (DMI) and1H MRSI (QELT), respectively.

The purpose of this study was to compare the dynamics of spatially resolved brain glucose metabolism, i.e., estimated concentration enrichment of deuterium labeled Glx (glutamate+glutamine) and Glc (glucose) acquired repeatedly in the same cohort of subjects using DMI at 7T and QELT at clinical 3T.

Methods

Five volunteers (4m/1f) were scanned in repeated sessions for 60 min after overnight fasting and 0.8g/kg oral [6,6’-2H2]-glucose administration using time-resolved 3D2H FID-MRSI with elliptical phase encoding at 7T and 3D1H FID-MRSI with a non-Cartesian concentric ring trajectory readout at clinical 3T.

Results

One hour after oral tracer administration regionally averaged deuterium labeled Glx4concentrations and the dynamics were not significantly different over all participants between 7T2H DMI and 3T1H QELT data for GM (1.29±0.15 vs. 1.38±0.26 mM, p=0.65 & 21±3 vs. 26±3 µM/min, p=0.22) and WM (1.10±0.13 vs. 0.91±0.24 mM, p=0.34 & 19±2 vs. 17±3 µM/min, p=0.48). Also, the observed time constants of dynamic Glc6data in GM (24±14 vs. 19±7 min, p=0.65) and WM (28±19 vs. 18±9 min, p=0.43) dominated regions showed no significant differences.

Between individual2H and1H data points a weak to moderate negative correlation was observed for Glx4concentrations in GM (r=-0.52, p<0.001), and WM (r=-0.3, p<0.001) dominated regions, while a strong negative correlation was observed for Glc6data GM (r=- 0.61, p<0.001) and WM (r=-0.70, p<0.001).

Conclusion

This study demonstrates that indirect detection of deuterium labeled compounds using1H QELT MRSI at widely available clinical 3T without additional hardware is able to reproduce absolute concentration estimates of downstream glucose metabolites and the dynamics of glucose uptake compared to2H DMI data acquired at 7T. This suggests significant potential for widespread application in clinical settings especially in environments with limited access to ultra-high field scanners and dedicated RF hardware.
Engineered autocrine signaling eliminates muscle cell FGF2 requirements for cultured meat production
Authors: Stout Andrew J. , Zhang Xiaoli , Letcher Sophia M. , Rittenberg Miriam L. , Shub Michelle , Chai Kristin M. , Kaul Maya , Kaplan David L.
Published: April 2023

Cultured meat is a promising technology that faces substantial cost barriers which are currently driven largely by the price of media components. Growth factors such as fibroblast growth factor 2 (FGF2) drive the cost of serum-free media for relevant cells including muscle satellite cells. Here, we engineered immortalized bovine satellite cells (iBSCs) for inducible expression of FGF2 and/or mutated RasG12Vin order to overcome media growth factor requirements through autocrine signaling. Engineered cells were able to proliferate over multiple passages in FGF2-free medium, thereby eliminating the need for this costly component. Additionally, cells maintained their myogenicity, albeit with reduced differentiation capacity. Ultimately, this offers a proof-of-principle for lower-cost cultured meat production through cell line engineering.
Selectivity filter mutations shift ion permeation mechanism in potassium channels
Authors: Mironenko Andrei , de Groot Bert L , Kopec Wojciech
Published: April 2023

Potassium (K+) channels combine high conductance with high ion selectivity. To explain this efficiency, two molecular mechanisms have been proposed. The 'direct knock-on' mechanism is defined by water-free K+ permeation and formation of direct ion-ion contacts in the highly conserved selectivity filter (SF). The 'soft knock-on' mechanism involves co-permeation of water and separation of K+ by water molecules. With the aim to distinguish between these mechanisms, crystal structures of two SF mutants in the KcsA channel - G77 and T75 - were published, where the arrangements of K+ ions and water display canonical soft knock-on configurations. These data were interpreted as evidence of the soft knock-on mechanism in wild-type channels (C. Tilegenova, et al., Structure, function, and ion-binding properties of a K+ channel stabilized in the 2,4-ion-bound configuration. Proceedings of the National Academy of Sciences 116, 16829-16834 (2019)). Here, we test this interpretation using molecular dynamics simulations of KcsA and its mutants. We show that, while a strictly water-free direct knock-on permeation is observed in the wild-type, conformational changes induced by these mutations lead to distinct ion permeation mechanisms, characterized by a co-permeation of K+ and water. These mechanisms are characterized by reduced conductance and impaired potassium selectivity, supporting the importance of full dehydration of potassium ions for the hallmark high conductance and selectivity of K+ channels. In general, we present a case where mutations introduced at the critical points of the permeation pathway in an ion channel drastically change its permeation mechanism in a non-intuitive manner.
The RNA helicase DDX1 associates with the nuclear RNA exosome and modulates R-loops
Authors: de Amorim Julia L. , Leung Sara W. , Haji-Seyed-Javadi Ramona , Hou Yingzi , Yu David S. , Ghalei Homa , Khoshnevis Sohail , Yao Bing , Corbett Anita H.
Published: April 2023

The RNA exosome is a ribonuclease complex that mediates both RNA processing and degradation. This complex is evolutionarily conserved, ubiquitously expressed, and required for fundamental cellular functions, including rRNA processing. The RNA exosome plays roles in regulating gene expression and protecting the genome, including modulating the accumulation of RNA-DNA hybrids (R-loops). The function of the RNA exosome is facilitated by cofactors, such as the RNA helicase MTR4, which binds/remodels RNAs. Recently, missense mutations in RNA exosome subunit genes have been linked to neurological diseases. One possibility to explain why missense mutations in genes encoding RNA exosome subunits lead to neurological diseases is that the complex may interact with cell- or tissue-specific cofactors that are impacted by these changes. To begin addressing this question, we performed immunoprecipitation of the RNA exosome subunit, EXOSC3, in a neuronal cell line (N2A) followed by proteomic analyses to identify novel interactors. We identified the putative RNA helicase, DDX1, as an interactor. DDX1 plays roles in double-strand break repair, rRNA processing, and R-loop modulation. To explore the functional connections between EXOSC3 and DDX1, we examined the interaction following double-strand breaks, and analyzed changes in R-loops in N2A cells depleted for EXOSC3 or DDX1 by DNA/RNA immunoprecipitation followed by sequencing (DRIP-Seq). We find that EXOSC3 interaction with DDX1 is decreased in the presence of DNA damage and that loss of EXOSC3 or DDX1 alters R-loops. These results suggest EXOSC3 and DDX1 interact during events of cellular homeostasis and potentially suppress unscrupulous expression of genes promoting neuronal projection.
A multi-dimensional selective landscape drives adaptive divergence between and within closely relatedPhloxspecies
Authors: Goulet-Scott Benjamin E. , Farnitano Matthew C. , Brown Andrea L. M. , Hale Charles O. , Blumstein Meghan , Hopkins Robin
Published: April 2023

Natural selection shapes diversity across micro and macro-evolutionary scales. Selection causes local adaptation across populations within species and is simultaneously responsible for much of the divergence between species. However, it is unclear if either the force of or the response to selection is the same or different across these scales. Here we show that natural selection drives adaptive divergence between closely related species in a pattern that is distinct from local adaptation within a species. We use reciprocal common-garden transplant experiments across three species ofPhloxwildflowers to show widespread adaptive divergence causing species to have highest fitness in their native habitats. Using provenance trials, we also find that one of thesePhloxspecies has strong local adaptation between populations. We compare the axes of divergence and selection between these two scales of diversity and discover that one suite of traits predicts fitness differences between species and that an independent suite of traits predicts fitness variation within species across individuals. Our work reveals how forces of selection can both drive key divergence between species, allowing for and causing speciation, while simultaneously causing extensive diversity that is maintained across populations within a species. The selection landscape is complex and multidimensional
Motif conservation, stability, and host gene expression are the main drivers of snoRNA expression across vertebrates
Authors: Fafard-Couture Étienne , Jacques Pierre-Étienne , Scott Michelle S.
Published: April 2023

Small nucleolar RNAs (snoRNAs) are structured noncoding RNAs present in multiple copies within eukaryotic genomes. snoRNAs guide chemical modifications on their target RNA and regulate processes like ribosome assembly and splicing. Most human snoRNAs are embedded within host gene introns, the remainder being independently expressed from intergenic regions. We recently characterized the abundance of snoRNAs and their host gene across several healthy human tissues and found that the level of most snoRNAs does not correlate with that of their host gene, with the observation that snoRNAs embedded within the same host gene often differ drastically in abundance. To better understand the determinants of snoRNA expression, we trained machine learning models to predict whether snoRNAs are expressed or not in human tissues based on more than 30 collected features related to snoRNAs and their genomic context. By interpreting the models’ predictions, we find that snoRNAs rely on conserved motifs, a stable global structure and terminal stem, and a transcribed locus to be expressed. We observe that these features explain well the varying abundance of snoRNAs embedded within the same host gene. By predicting the expression status of snoRNAs across several vertebrates, we notice that only one-third of all annotated snoRNAs are expressed per genome, as in humans. Our results suggest that ancestral snoRNAs disseminated within vertebrate genomes, sometimes leading to the development of new functions and a probable gain in fitness and thereby conserving features favorable to the expression of these few snoRNAs, the large remainder often degenerating into pseudogenes.
Enhancing employee advocacy of the firm's corporate social responsibility (CSR) activities
Authors: Chomvilailuk Rojanasak , Butcher Ken
Published: April 2023

Purpose

The paper aims to investigate how perceived psychological benefits from employee participation in corporate social responsibility activities affect organizational citizenship behavior across two Asia–Pacific countries with different national cultures.

Design/methodology/approach

A stakeholder relationship model, based on social exchange theory, underpinned the investigation that also tested the mediating role of organizational pride. In a cross-cultural context, data were collected from 319 full-time employees in Thailand and the US and analyzed with SEM-PLS.

Findings

Anticipated psychological benefits of hedonic value and perceived community value were found to be significant antecedents of organizational citizenship behaviors, operationalized as customer-directed CSR advocacy. Organizational pride played a partial mediating role.

Originality/value

This study addresses a lack of micro-level CSR research into the relationship between psychological benefits of employee participation in CSR and organizational citizenship behavior. Specifically, this is the first study to link CSR drivers with customer-directed employee advocacy of the firms CSR activities. The study is also the first to compare relationships between an Asian and Western context for CSR drivers of organizational citizenship behaviors.
Value relevance of earnings and book value of equity in profit versus loss reporting firms: significance of intangible intensity
Authors: Kumari Pooja , Mishra Chandra Sekhar
Published: April 2023

Purpose

This study aims to investigate how the intangible intensive nature of firms affects the value relevance of earnings and the book value of equity between profit- and loss-reporting firms. The study also examines how firms’ intangible intensity affects the value relevance of R&D outlays between profit- and loss-reporting firms.

Design/methodology/approach

An empirical analysis based on Ohlson’s (1995) framework is used. A total of 54,421 firm-year observations of Indian listed firms from financial years 1992–2016 constitute the study sample.

Findings

The findings suggest that the difference in the value relevance of earnings and the book value of equity between profit- and loss-reporting firms is more significant in non-intangible intensive firms than in intangible firms. Specifically, earnings are more value relevant in profit-reporting and non-intangible intensive firms, whereas book value of equity is more value relevant in loss-reporting and intangible intensive firms. The results also suggest that the difference in the incremental value relevance of R&D information between profit- and loss-making firms is higher in intangible intensive firms than in non-intangible intensive firms.

Practical implications

The findings of this study can help managers, standard-setters and investors make effective decisions.

Originality/value

This study offers insights into the impact of intangible intensity on the value relevance of aggregated and disaggregated accounting information between profit- and loss-making firms in institutional settings where capitalization of R&D expenditures is allowed.
Why not reprocessed: identifying factors limiting the uptake of reprocessed structural timber
Authors: Tennakoon Gihan Anuradha , Rameezdeen Raufdeen , Chileshe Nicholas
Published: April 2023

Purpose

Timber waste from construction is downcycled into non-structural products, incinerated for energy generation or disposed of in landfills. Existing literature highlights that the use of reprocessed timber for structural purposes is limited. Therefore, this study aims to focus on identifying factors limiting reprocessed structural timber (RST) uptake amongst construction professionals in Australia.

Design/methodology/approach

Current literature shows that the use of reprocessed materials (RMs) depends on user-specific personal factors and broader contextual factors. Therefore, data collection and analysis were based on the attitude-behaviour-context (ABC) theory, which affirms this relationship between personal and contextual factors in determining pro-environmental behaviours (PEBs). A qualitative research approach was adopted, considering limitations with industry expertise and the need for developing an in-depth understanding of limiting factors. Twenty semi-structured interviews were conducted amongst construction professionals experienced in using reprocessed materials, while the thematic analysis technique was used to analyse interview findings.

Findings

Personal factors that limit the uptake of RST include negative cost and quality perceptions, risk appetite, the tendency to maintain the status-quo, limited decision-making capability and lack of skills and expertise, while contextual factors include higher prices, poor and uncertain quality, limitations with information availability, under-developed supply and drawbacks in the regulatory environment.

Originality/value

The current study is amongst the first to explore the uptake of reprocessed timber for structural uses in Australia. The findings can be utilised to create a stronger demand for RST by directly addressing personal and contextual factors that constrain construction professionals from using RST.
Implicit integration of an anisotropic egg-shaped elastoplastic model for saturated soft clay
Authors: Ju Luying , Yan Zihai , Wu Mingming , Zhang Gangping , Yan Jiajia , Yu Tianci , Ding Pan , Xu Riqing
Published: April 2023

Purpose

The purpose of this paper is to suggest an implicit integration method for updating the constitutive relationships in the newly proposed anisotropic egg-shaped elastoplastic (AESE) model and to apply it in ABAQUS.

Design/methodology/approach

The implicit integration algorithm based on the Newton–Raphson method and the closest point projection scheme containing an elastic predictor and plastic corrector are implemented in the AESE model. Then, the integration code for this model is incorporated into the commercial finite element software ABAQUS through the user material subroutine (UMAT) interface to simulate undrained monotonic triaxial tests for various saturated soft clays under different consolidation conditions.

Findings

The comparison between the simulated results from ABAQUS and the experimental results demonstrates the satisfactory performance of this implicit integration algorithm in terms of effectiveness and robustness and the ability of the proposed model to predict the characteristics of soft clay.

Research limitations/implications

The rotational hardening rule in the AESE model together with the implicit integration algorithm cannot be considered.

Originality/value

The singularity problem existing in most elastoplastic models is eliminated by the closed, smooth and flexible anisotropic egg-shaped yield surface form in the AESE model. In addition, this notion leads to an efficient implicit integration algorithm for updating the highly nonlinear constitutive equations for unsaturated soft clay.
Business families do it differently! Navigating cycles and waves of family firm internationalization
Authors: Calabrò Andrea , Mayrhofer Ulrike , Valentino Alfredo
Published: April 2023

Purpose

This paper aims at extending the debate on family firm internationalization by identifying cycles and waves of their internationalization processes with a specific focus on de-internationalization and re-internationalization.

Design/methodology/approach

Building on the Uppsala model and the resource-based view, this study analyzes the cycles and waves of internationalization of 26 German family firms in the Chinese market. Semi-structured interviews with top managers of the selected case firms were conducted, and secondary sources were used to triangulate the collected data.

Findings

The findings highlight the heterogeneity of family firm internationalization processes. Indeed, some family firms follow the sequential approach of the Uppsala model, while others choose to de-internationalize and then re-internationalize their activities. Their cycles and waves of internationalization can be explained by internal and external triggers.

Originality/value

This article contributes to the family firm internationalization literature by investigating how family firm characteristics and environmental factors shape internationalization, de-internationalization and re-internationalization paths. The novel findings enrich theoretical assumptions on family firm internationalization and highlight their varying internationalization processes, which can be explained by firm-specific characteristics, notably their unique family resources and socioemotional wealth, and contextual factors.