bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic and transcriptional regulations prime cell fate before division during human pluripotent stem cell differentiation
Authors: Madrigal Pedro , Deng Siwei , Feng Yuliang , Militi Stefania , Goh Kim Jee , Nibhani Reshma , Grandy Rodrigo , Osnato Anna , Ortmann Daniel , Brown Stephanie , Pauklin Siim 
Published: January 2023

AbstractStem cells undergo cellular division during their differentiation to produce daughter cells with a new cellular identity. However, the epigenetic events and molecular mechanisms occurring between consecutive cell divisions have been insufficiently studied due to technical limitations. Here, using the FUCCI reporter we developed a cell-cycle synchronised human pluripotent stem cell (hPSC) differentiation system for uncovering epigenome and transcriptome dynamics during the first two divisions leading to definitive endoderm. We observed that transcription of key differentiation markers occurs before cell division, while chromatin accessibility analyses revealed the early inhibition of alternative cell fates. We found that Activator protein-1 members controlled by p38/MAPK signalling are necessary for inducing endoderm while blocking cell fate shifting toward mesoderm, and that enhancers are rapidly established and decommissioned between different cell divisions. Our study has practical biomedical utility for producing hPSC-derived patient-specific cell types since p38/MAPK induction increased the differentiation efficiency of insulin-producing pancreatic beta-cells.
The Pga59 cell wall protein is an amyloid forming protein involved in adhesion and biofilm establishment in the pathogenic yeast Candida albicans
Authors: Mourer Thierry , El Ghalid Mennat , Pehau-Arnaudet Gérard , Kauffmann Brice , Loquet Antoine , Brûlé Sébastien , Cabral Vitor , d’Enfert Christophe , Bachellier-Bassi Sophie 
Published: January 2023

AbstractThe human commensal fungusCandida albicanscan attach to epithelia or indwelling medical devices and form biofilms, that are highly tolerant to antifungal drugs and can evade the immune response. The cell surface protein Pga59 has been shown to influence adhesion and biofilm formation. Here, we present evidence that Pga59 displays amyloid properties. Using electron microscopy, staining with an amyloid fibre-specific dye and X-ray diffraction experiments, we showed that the predicted amyloid-forming region of Pga59 is sufficient to build up an amyloid fibre in vitro and that recombinant Pga59 can also adopt a cross-β amyloid fibre architecture. Further, mutations impairing Pga59 amyloid assembly led to diminished adhesion to substrates and reduced biofilm production. Immunogold labelling on amyloid structures extracted fromC. albicansrevealed that Pga59 is used by the fungal cell to assemble amyloids within the cell wall in response to adhesion. Altogether, our results suggest that Pga59 amyloid properties are used by the fungal cell to mediate cell-substrate interactions and biofilm formation.
Chronic low-dose Δ9-tetrahydrocannabinol (THC) treatment stabilizes dendritic spines in 18-month-old mice
Authors: Komorowska-Müller Joanna Agnieszka , Gellner Anne-Kathrin , Ravichandran Kishore Aravind , Bilkei-Gorzo Andras , Zimmer Andreas , Stein Valentin 
Published: January 2023

AbstractCognitive functions decline during aging. This decline could be caused by changes in dendritic spine stability and altered spine dynamics. Previously, we have shown that a low dose chronic THC treatment improves learning abilities in old whereas impairs learning abilities in young mice. The mechanism underlying this age-dependent effect is not known. Dendritic spine stability is a key for memory formation, therefore we hypothesized that THC affects spine dynamics in an age-dependent manner. We applied longitudinal 2-photon in vivo imaging to 3- and 18-month-old mice treated with 3 mg/kg/day of THC for 28 days via an osmotic pump. We imaged the same dendritic segments before, during and after the treatment and assessed changes in spine density and stability. We now show that in old mice THC improved spine stability resulting in a long-lasting increase in spine density. In contrast, in young mice THC transiently increased spine turnover and destabilized the spines.
HDF1, a novel flowering time regulator identified in a mutant suppressing sensitivity to red light reduced 1 early flowering
Authors: Johansson Mikael , Steffen Alexander , Lewinski Martin , Kobi Natalie , Staiger Dorothee 
Published: January 2023

AbstractArabidopsis SENSITIVITY TO RED LIGHT REDUCED 1 (SRR1) delays the transition from vegetative to reproductive development in noninductive conditions. A second-site suppressor screen for novel genes that overcome early flowering of srr1-1 identified a range of suppressor of srr1-1 mutants flowering later than srr1-1 in short photoperiods. Here, we focus on mutants flowering with leaf numbers intermediate between srr1-1 and Col. Ssm67 overcomes srr1-1 early flowering independently of day-length and ambient temperature. Full-genome sequencing and linkage mapping identified a causative SNP in a gene encoding a Haloacid dehalogenase superfamily protein, named HAD-FAMILY REGULATOR OF DEVELOPMENT AND FLOWERING 1 (HDF1). Both, ssm67 and hdf1-1 show increased levels of FLC, indicating that HDF1 is a novel regulator of this floral repressor. HDF1 regulates flowering largely independent of SRR1, as the effect is visible in srr1-1 and in Col, but full activity on FLC may require SRR1. Furthermore, srr1-1 has a delayed leaf initiation rate that is dependent on HDF1, suggesting that SRR1 and HDF1 act together in leaf initiation. Another mutant flowering intermediate between srr1-1 and wt, ssm15, was identified as a new allele of ARABIDOPSIS SUMO PROTEASE 1, previously implicated in the regulation of FLC stability.
Epidemiological role of novel and already known ‘Ca. P. solani’ cixiid vectors in rubbery taproot disease of sugar beet in Serbia
Authors: Kosovac Andrea , Ćurčić Živko , Stepanović Jelena , Rekanović Emil , Duduk Bojan 
Published: January 2023

AbstractRubbery taproot disease (RTD) of sugar beet was recently associated with the plant pathogenic bacterium ‘Candidatus Phytoplasma solani’ (CaPsol) and reported throughout the Pannonian Plain with variations in severity. Tracing CaPsol epidemiological pathways was performed in the experimental sugar beet field in Rimski Šančevi (Serbia) in 2020–2021, where an RTD outbreak was recently recorded. A molecular epidemiology approach was applied to the study of three RTD occurrence scenarios: epidemic, non-epidemic and ‘absence of RTD’. As a result, Hyalesthes obsoletus ex Convolvulus arvensis was detected as a CaPsol vector to sugar beet, while two other cixiids were identified for the first time as vectors of the CaPsol-induced plant disease in crops: Reptalus quinquecostatus and R. cuspidatus. R. quinquecostatus was proposed culpable for the 2020 RTD epidemic outbreak in Rimski Šančevi when dSTOLg CaPsol strain predominated in the RTD-affected sugar beet, whereas R. cuspidatus had a negligible role in RTD occurrence and displayed ambiguous involvement in CaPsol epidemiology on a wider scale. The temporal discrepancy of the offset of CaPsol dissemination and disease occurrence is the main obstacle in predicting CaPsol-induced diseases. Predicting disease occurrence and severity can only be achieved by gaining a better understanding of CaPsol epidemiological pathways and insect vectors involved in disease outbreaks.
N-terminal domain of tyrosyl-DNA phosphodiesterase I regulates topoisomerase I-induced toxicity in cells
Authors: Brettrager Evan J. , Cuya Selma M. , Tibbs Zachary E. , Zhang Jun , Falany Charles N. , Aller Stephen G. , van Waardenburg Robert C. A. M. 
Published: January 2023

AbstractTyrosyl-DNA phosphodiesterase I (Tdp1) hydrolyzes phosphodiester-linked adducts from both ends of DNA. This includes the topoisomerase I (TOP1)-DNA covalent reaction intermediate that is the target of the camptothecin class of chemotherapeutics. Tdp1 two-step catalysis is centered on the formation of a Tdp1-DNA covalent complex (Tdp1cc) using two catalytic histidines. Here, we examined the role of the understudied, structurally undefined, and poorly conserved N-terminal domain (NTD) of Tdp1 in context of full-length protein in its ability to remove TOP1cc in cells. Using toxic Tdp1 mutants, we observed that the NTD is critical for Tdp1’s ability to remove TOP1-DNA adducts in yeast. Full-length and N-terminal truncated Tdp1 mutants showed similar expression levels and cellular distribution yet an inversed TOP1-dependent toxicity. Single turnover catalysis was significantly different between full-length and truncated catalytic mutants but not wild-type enzyme, suggesting that Tdp1 mutants depend on the NTD for catalysis. These observations suggest that the NTD plays a critical role in the regulation of Tdp1 activity and interaction with protein-DNA adducts such as TOP1cc in cells. We propose that the NTD is a regulatory domain and coordinates stabilization of the DNA-adducted end within the catalytic pocket to access the phosphodiester linkage for hydrolysis.
Predicting wind-driven spatial deposition through simulated color images using deep autoencoders
Authors: Fernández-Godino M. Giselle , Lucas Donald D. , Kong Qingkai 
Published: January 2023

AbstractFor centuries, scientists have observed nature to understand the laws that govern the physical world. The traditional process of turning observations into physical understanding is slow. Imperfect models are constructed and tested to explain relationships in data. Powerful new algorithms can enable computers to learn physics by observing images and videos. Inspired by this idea, instead of training machine learning models using physical quantities, we used images, that is, pixel information. For this work, and as a proof of concept, the physics of interest are wind-driven spatial patterns. These phenomena include features in Aeolian dunes and volcanic ash deposition, wildfire smoke, and air pollution plumes. We use computer model simulations of spatial deposition patterns to approximate images from a hypothetical imaging device whose outputs are red, green, and blue (RGB) color images with channel values ranging from 0 to 255. In this paper, we explore deep convolutional neural network-based autoencoders to exploit relationships in wind-driven spatial patterns, which commonly occur in geosciences, and reduce their dimensionality. Reducing the data dimension size with an encoder enables training deep, fully connected neural network models linking geographic and meteorological scalar input quantities to the encoded space. Once this is achieved, full spatial patterns are reconstructed using the decoder. We demonstrate this approach on images of spatial deposition from a pollution source, where the encoder compresses the dimensionality to 0.02% of the original size, and the full predictive model performance on test data achieves a normalized root mean squared error of 8%, a figure of merit in space of 94% and a precision-recall area under the curve of 0.93.
Asymptotic Pomeranchuk instability of Fermi liquids in half-filled Landau levels
Authors: Quintanilla Jorge , Ciftja Orion 
Published: January 2023

AbstractWe present a theory of spontaneous Fermi surface deformations for half-filled Landau levels (filling factors of the form $$\nu =2 \, n+1/2$$

ν
=
2

n
+
1
/
2

). We assume the half-filled level to be in a compressible, Fermi liquid state with a circular Fermi surface. The Landau level projection is incorporated via a modified effective electron-electron interaction and the resulting band structure is described within the Hartree-Fock approximation. We regulate the infrared divergences in the theory and probe the intrinsic tendency of the Fermi surface to deform through Pomeranchuk instabilities. We find that the corresponding susceptibility never diverges, though the system is asymptotically unstable in the $$n \rightarrow \infty $$

n
→
∞

limit.
Non-task expert physicians benefit from correct explainable AI advice when reviewing X-rays
Authors: Gaube Susanne , Suresh Harini , Raue Martina , Lermer Eva , Koch Timo K. , Hudecek Matthias F. C. , Ackery Alun D. , Grover Samir C. , Coughlin Joseph F. , Frey Dieter , Kitamura Felipe C. , Ghassemi Marzyeh , Colak Errol 
Published: January 2023

AbstractArtificial intelligence (AI)-generated clinical advice is becoming more prevalent in healthcare. However, the impact of AI-generated advice on physicians’ decision-making is underexplored. In this study, physicians received X-rays with correct diagnostic advice and were asked to make a diagnosis, rate the advice’s quality, and judge their own confidence. We manipulated whether the advice came with or without a visual annotation on the X-rays, and whether it was labeled as coming from an AI or a human radiologist. Overall, receiving annotated advice from an AI resulted in the highest diagnostic accuracy. Physicians rated the quality of AI advice higher than human advice. We did not find a strong effect of either manipulation on participants’ confidence. The magnitude of the effects varied between task experts and non-task experts, with the latter benefiting considerably from correct explainable AI advice. These findings raise important considerations for the deployment of diagnostic advice in healthcare.
Design and tribological performance of short S-Glass fibre reinforced biocomposites on the influence of fibre length and concentration
Authors: Raju  , Loy Chee Wah , Cho Kiho , Farrar Paul , Prusty B. Gangadhara 
Published: January 2023

AbstractFibre-reinforced biocomposites usage has gained prominence over the past decade. Although higher fracture toughness was observed when fibres were added to biocomposites, material degradation could occur due to filler and fibre content intolerance in the biocomposite matrix. Optimisation of resin-fibre-filler ratios helps in increasing the tribological performance of high load-bearing applications. However, the tribological performance is less understood due to limited in-vitro studies on the effect of fibre microstructures. A comprehensive investigation of the reciprocating and rotary wear behaviour of different compositions was carried out by varying fibre (0%, 5%, 10% and 15%) to particulate filler (40%, 45%, 50%, and 55%) weight fractions. The investigation aimed to identify the optimal composition of fibre-reinforced biocomposites based on the in-vitro ball-on-disc reciprocating and rotary wear tests in the presence of modified Fusayama solution. The cross-sectional areas of wear tracks were analysed using laser microscopy and scanning electron microscopy techniques to assess the surface morphology and subsurface damage of the wear tracks on biocomposites and the antagonist. The numerical results were statistically analysed using two-way ANOVA followed by a posthoc Tukey’s test (p = 0.05). The results showed a combination of adhesive, abrasive and fatigue wear for all the tested Groups. The friction coefficient had a longer transient period for the 5 wt% and 10 wt% Groups. Based on the surface roughness, coefficient of friction, SEMs, specific wear rate, and ease of manufacturing, the threshold limit for fibre loading was found to be 10 wt%. The rotary test had a considerably lower specific wear rate compared to the reciprocating test. Fibre weight fraction was found to be the influencing factor of the abrasive wear behaviour compared to fibre length for the tested Groups.
Comparing the SARS-CoV-2-specific antibody response in human milk after homologous and heterologous booster vaccinations
Authors: Mulleners Sien J. , Juncker Hannah G. , Ruhé Eliza J. M. , Korosi Aniko , van Goudoever Johannes B. , van Gils Marit J. , van Keulen Britt J. 
Published: January 2023

AbstractHuman milk contains SARS-CoV-2-specific antibodies after COVID-19 vaccination. These milk antibodies decrease several months post-vaccination. Whether booster immunization restores human milk antibody levels, potentially offering prolonged passive immunity for the infant, remains unknown. In this prospective follow-up study, we investigated the longitudinal SARS-CoV-2-specific antibody response in human milk of 26 lactating women who received a COVID-19 booster dose of an mRNA-based vaccine. Moreover, we evaluated whether the booster-induced human milk antibody response differs for participants who received a similar or different vaccine type in their primary vaccination series. All participants (100%) who received a homologous booster vaccination showed SARS-CoV-2-specific immunoglobulin A (IgA) and immunoglobulin G (IgG) in their milk. Heterologous booster vaccination resulted in milk conversion for 9 (69%) and 13 (100%) participants for IgA and IgG respectively. Findings of this study indicate that both homologous and heterologous boosting schedules have the potential to enhance SARS-CoV-2-specific IgA and IgG in human milk.
Emergent behaviour and neural dynamics in artificial agents tracking odour plumes
Authors: Singh Satpreet H. , van Breugel Floris , Rao Rajesh P. N. , Brunton Bingni W. 
Published: January 2023

AbstractTracking an odour plume to locate its source under variable wind and plume statistics is a complex task. Flying insects routinely accomplish such tracking, often over long distances, in pursuit of food or mates. Several aspects of this remarkable behaviour and its underlying neural circuitry have been studied experimentally. Here we take a complementary in silico approach to develop an integrated understanding of their behaviour and neural computations. Specifically, we train artificial recurrent neural network agents using deep reinforcement learning to locate the source of simulated odour plumes that mimic features of plumes in a turbulent flow. Interestingly, the agents’ emergent behaviours resemble those of flying insects, and the recurrent neural networks learn to compute task-relevant variables with distinct dynamic structures in population activity. Our analyses put forward a testable behavioural hypothesis for tracking plumes in changing wind direction, and we provide key intuitions for memory requirements and neural dynamics in odour plume tracking.
Response of cyanobacterial mats to ambient phosphate fluctuations: phosphorus cycling, polyphosphate accumulation and stoichiometric flexibility
Authors: Jentzsch Laura , Grossart Hans-Peter , Plewe Sascha , Schulze-Makuch Dirk , Goldhammer Tobias 
Published: January 2023

Abstract
Cyanobacterial mats inhabit a variety of aquatic habitats, including the most extreme environments on Earth. They can thrive in a wide range of phosphorus (P) levels and are thus important players for ecosystem primary production and P cycling at the sediment-water interface. Polyphosphate (polyP), the major microbial P storage molecule, is assigned a critical role in compensating for phosphate fluctuations in planktonic cyanobacteria, but little is known about potentially analogous mechanisms of mat-forming cyanobacteria. To investigate acclimation strategies of cyanobacterial mats to fluctuating phosphate concentrations, laboratory batch experiments were conducted, in which the cosmopolitan mat-forming, marine cyanobacterium Sodalinema stali was exposed to low dissolved P concentrations, followed by a P pulse. Our results show that the cyanobacteria dynamically adjusted cellular P content to ambient phosphate concentrations and that they had accumulated polyP during periods of high phosphate availability, which was subsequently recycled to sustain growth during phosphate scarcity. However, following the depletion of dispensable cellular P sources, including polyP, we observed a reallocation of P contained in DNA into polyP, accompanied by increasing alkaline phosphatase activity. This suggests a change of the metabolic focus from growth towards maintenance and the attempt to acquire organic P, which would be naturally contained in the sediment. P overplus uptake following a simulated P pulse further suggests that Sodalinema-dominated mats exhibit elaborated mechanisms to cope with severe P fluctuations to overcome unfavourable environmental conditions, and potentially modulate critical P fluxes in the aquatic cycle.
Association of GCK (rs1799884), GCKR (rs780094), and G6PC2 (rs560887) Gene Polymorphisms with Type 2 Diabetes among Malay Ethnics
Authors: Ansari Neda , Ramachandran Vasudevan , Mohamad Nur Afiqah , Salim Elnaz , Ismail Patimah , Hazmi Mohamad , Mat Liyana Najwa Inchee 
Published: January 2023

Abstract
Background Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder, and the underlying causes remain unknown and have not been fully elucidated. Several candidate genes have been associated with T2DM in various populations with conflicting results. The variations found in glucokinase (GCK), glucokinase regulatory protein (GCKR), and glucose-6-phosphatase 2 (G6PC2) genes were not well studied, particularly among Asians.
Aims The main objective of this study was to determine the candidate genetic polymorphisms of GCK (rs1799884), GCKR (rs780094), and G6PC2 (rs560887) genes in T2DM among Malay ethnics.
Methods In this candidate gene association study, a total of 180 T2DM subjects and 180 control subjects were recruited to determine the genotypes using polymerase chain reaction-restriction fragment length polymorphism and Taqman probe assay methods. Genotype and allele frequencies in case and control samples were compared using the chi-squared test to determine a significant difference.
Results The body mass index, fasting blood glucose, hemoglobin A1c, systolic and diastolic blood pressure, and total cholesterol were significantly different (p < 0.05) between T2DM and control subjects. The genotypic and allelic frequencies of GCK (rs1799884), GCKR (rs780094), and G6PC2 (rs560887) gene polymorphisms were significantly different between T2DM and controls (p < 0.05).
Conclusion Hence, rs1799884 of GCK gene and rs780094 of GCKR gene and rs560887 of the G6PC2 gene are possible genetic biomarkers in T2DM development among Malay ethnics in Malaysia.
The Role of the Microbiome in the Etiology of Inflammatory Bowel Diseases
Authors: Halper-Stromberg Ariel , Dalal Sushila R. 
Published: January 2023

AbstractInflammatory bowel diseases (IBDs) result from dysregulated immune responses to environmental and microbial triggers in genetically susceptible hosts. Many clinical observations and animal studies support the role of the microbiome in the pathogenesis of IBD. Restoration of the fecal stream leads to postoperative Crohn's recurrence, while diversion can treat active inflammation. Antibiotics can be effective in prevention of postoperative Crohn's recurrence and in pouch inflammation. Several gene mutations associated with Crohn's risk lead to functional changes in microbial sensing and handling. However, the evidence linking the microbiome to the IBD is largely correlative, given the difficulty in studying the microbiome before disease occurs. Attempts to modify the microbial triggers of inflammation have had modest success to date. Exclusive enteral nutrition can treat Crohn's inflammation though no whole food diet to date has been shown to treat inflammation. Manipulation of the microbiome through fecal microbiota transplant and probiotics have had limited success. Further focus on early changes in the microbiome and functional consequences of microbial changes through the study of metabolomics are needed to help advance the field.