bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Machine Learning Classifier to Identify and Prioritise Genes Associated with Cardiac Development
Authors: Kabir Mitra , Hartill Verity , Farr Gist H. , Shaikh Qureshi Wasay Mohiuddin , Baross Stephanie L. , Doig Andrew J. , Talavera David , Keavney Bernard D. , Maves Lisa , Johnson Colin A. , Hentges Kathryn E. 
Published: November 2024

AbstractCongenital heart disease (CHD) is a major cause of infant mortality and presents life-long challenges to individuals living with these conditions. Genetic causes are known for only a minority of types of CHD. Discovering further genetic causes is limited by challenges in prioritising candidate CHD genes. We examined a wide range of features of mouse genes, including sequence characteristics, protein localisation and interaction data, developmental expression data and gene ontology annotations. Many features differ between cardiac development and non-cardiac genes, suggesting that these two gene types can be distinguished by their attributes. Therefore, we developed a supervised machine learning (ML) method to identifyMus musculusgenes with a high probability of being involved in cardiac development. These genes, when mutated, are candidates for causing human CHD. Our classifier showed a cross-validation accuracy of 81% in detecting cardiac and non-cardiac genes. From our classifier we generated predictions of the cardiac development association status for all protein-coding genes in the mouse genome. We also cross-referenced our predictions with datasets of known human CHD genes, determining which are orthologues of predicted mouse cardiac genes. Our predicted cardiac genes have a high overlap with human CHD genes. Thus, our predictions could inform the prioritisation of genes when evaluating CHD patient sequence data for genetic diagnosis. Knowledge of cardiac developmental genes may speed up reaching a genetic diagnosis for patients born with CHD.Author SummaryCongenital heart disease arises during pregnancy when the heart has formed incorrectly. These malformations affect ∼1% of newborns. Yet, despite their frequency, the underlying causes are still not known in many cases. It is clear that genetic factors contribute to these defects, and increasingly DNA sequencing is used to attempt to determine if an individual has a genetic change causative of their condition. However, analysis of patient sequence data often reveals changes that are difficult to interpret due to a lack of knowledge of the function of the gene harbouring a sequence change. We aimed to facilitate the process of sequence evaluation by predicting which genes of unknown function are likely involved in heart formation. Our predictions agree with novel experimental evidence about genes needed for heart development. We found that when mutated, a high proportion of the predicted cardiac genes do indeed cause heart defects. This result suggests that our predictions may be informative for expanding our understanding of the genetic basis of congenital heart disease.
Physiological stress response to sulfide exposure of freshwater anaerobic methanotrophic archaea
Authors: Echeveste Medrano Maider J. , Lee Sarah , de Graaf Rob , Holohan B. Conall , Sánchez-Andrea Irene , Jetten Mike S. M. , Welte Cornelia U. 
Published: November 2024

AbstractFreshwater wetlands and coastal sediments are becoming hotspots for the emission of the greenhouse gas methane. Eutrophication-induced deposition of organic matter leads to elevated methanogenesis and sulfate reduction, thereby increasing the concentrations of methane and toxic sulfide, respectively. However, the effects of sulfide stress on the anaerobic methanotrophic biofilter have not been well explored. Here, we show how an enrichment culture dominated by the freshwater anaerobic methane-oxidizing archaeon ‘Candidatus(Ca.) Methanoperedens’ responds to short-term and long-term exposure to sulfide in a bioreactor. The methane-oxidizing activity decreased to 45% and 20% but partially recovered to 70% and 30% within 5 days after short- and long-term sulfide exposure, respectively. Metagenomics indicated that ‘Ca.Methanoperedens’ remained dominant in the enrichment throughout the entire experiment. The first short-term sulfide pulse led to increased expression of genes encoding for sulfide detoxification by low abundant community members, whereas long-term exposure resulted in upregulation of ‘Ca.Methanoperedens’ genes encoding sulfite reductases of Group III (Dsr-LP). ‘Ca.Methanoperedens’ consumed Polyhydroxyalkanoates during long-term sulfide exposure, possibly to aid in stress adaptation. Together, these results provide a valuable baseline for understanding fundamental ecophysiological adaptations in sulfate- and nitrate-rich aquatic ecosystems.Short synopsis statementThis study investigated how freshwater anaerobic methanotrophic archaea responded to sulfide exposure, revealing a transient inhibition and physiological adaptation mechanisms.
Donor embryonic stem cells impede host epiblast specification in 8-cell stage chimeras by crowding and FGF4 signalling
Authors: Strawbridge Stanley E. , Schrattel Anna Katharina , Humphreys Peter , Jones Ken A. , Artus Jérôme , Hadjantonakis Anna-Katerina , Fletcher Alexander G. , Nichols Jennifer 
Published: November 2024

ABSTRACTDuring mouse embryo compaction, outer cells become trophectoderm, while inner cells form the inner cell mass (ICM), later differentiating into primitive endoderm and epiblast - source of embryonic stem cells (ESCs) - during blastocyst formation. Trophectoderm specification is driven by position-governed polarisation, while primitive endoderm specification is positively regulated by FGF4 signalling from the ICM and epiblast. When injected into an 8-cell stage morula, ESCs can exclude host cells from the epiblast, leading to mice derived entirely from these cells. While evidence suggests roles for ESC-produced FGF4 and physical crowding in host cell displacement from the ICM, the interplay between these possible mechanisms has yet to be dissected, in part due to the lack of studies usingFgf4-/-ESCs. Here, we combine chimaera titration assays with mathematical modelling to study these mechanisms of host cell displacement. BothFgf4+/+andFgf4-/-ESCs displaced host cells from the epiblast, while onlyFgf4-/-injected embryos reduced primitive endoderm and increased trophectoderm, indicating sequential exclusion by displacement crowding followed by FGF4 signalling.SUMMARY STATEMENTIn mouse blastocyst chimeras, donor cells displace host cells from the epiblast by a combination of crowding and FGF4 signalling.
Spatial Proteomics By Parallel Accumulation-Serial Fragmentation Supported MALDI MS/MS Imaging: A First Glance Into Multiplexed and Spatial Peptide Identification
Authors: Li Mujia Jenny , Meyer Larissa Chiara , Meier Nadine , Witte Jannik , Maldacker Maximilian , Seredynska Adrianna , Schueler Julia , Schilling Oliver , Föll Melanie Christine 
Published: November 2024

AbstractRATIONALEIn spatial proteomics, matrix-assisted laser desorption/ionization (MALDI) imaging enables rapid and cost-effective peptide measurements. Yet, in situ peptide identification remains challenging. Therefore, this study aims to integrate the trapped ion mobility spectrometry (TIMS)-based parallel accumulation-serial fragmentation (PASEF) into MALDI imaging of tryptic peptides to enable multiplexed MS/MS imaging.METHODSAn initial MALDI TIMS MS1 survey measurement was performed, followed by a manual generation of a precursor list containing mass over charge values and ion mobility windows. Inside the dual TIMS system, submitted precursors were trapped, separately eluted by their ion mobility and analyzed in a quadrupole time-of-flight device, thereby enabling multiplexed MALDI MS/MS imaging. Finally, precursors were identified by peptide to spectrum matching.RESULTSThis study presents the first multiplexed MALDI TIMS MS/MS imaging (iprm-PASEF) of tryptic peptides. Its applicability was showcased on two histomorphologically distinct tissue specimens in a 4-plex and 5-plex setup. Precursors were successfully identified by the search engine MASCOT in one single MALDI imaging experiment for each respective tissue. Peptide identifications were corroborated by liquid-chromatography tandem mass spectrometry experiments and fragment co-localization analyses.CONCLUSIONSIn this study, we present a novel pipeline, based on iprm-PASEF that allows the multiplexed and spatial identification of tryptic peptides in MALDI imaging. Hence, it marks a first step towards the integration of MALDI imaging into the emerging field of spatial proteomics.
Small molecule oxybutynin rescues proliferative capacity of complex III-defective MPCs
Authors: Qu Yue , Edwards Kaydine , Li Muying , Liu Yang , Tsai Pei-Yin , Cheng Chloe , Blum Jamie , Acor Noel , Oshoe Tenzin , Rooney Kyra , Walter Claire , Thirumalaikumar Venkatesh , Thalacker-Mercer Anna , Skyricz Aleksandra , Barrow Joeva J 
Published: November 2024

ABSTRACTMitochondrial disease encompasses a group of genetically inherited disorders hallmarked by an inability of the respiratory chain to produce sufficient ATP. These disorders present with multisystemic pathologies that predominantly impact highly energetic tissues such as skeletal muscle. There is no cure or effective treatment for mitochondrial disease. We have discovered a small molecule known as oxybutynin that can bypass Complex III mitochondrial dysfunction in primary murine and human skeletal muscle progenitor cells (MPCs). Oxybutynin administration improves MPC proliferative capacity, enhances cellular glycolytic function, and improves myotube formation. Mechanistically, results from our isothermal shift assay indicates that oxybutynin interacts with a suite of proteins involved in mRNA processing which then trigger the upregulation biological pathways to circumvent CIII mitochondrial dysfunction. Taken together, we provide evidence for the small molecule oxybutynin as a potential therapeutic candidate for the future treatment of CIII mitochondrial dysfunction.
Unequal mitochondrial segregation promotes asymmetric fates during neurogenesis
Authors: Bunel Benjamin , Goiame Rosette , Morin Xavier , Fischer Evelyne 
Published: November 2024

AbstractAsymmetric divisions of vertebrate neural progenitors are critical for generating neurons while preserving the stem cell pool, ensuring proper central nervous system development. It was previously shown that the post-mitotic remodeling of mitochondrial activity in daughter cells influences neural fates. In this study, we demonstrate that unequal distribution of mitochondria during asymmetric mitosis plays a decisive role in triggering this differentiation process. Using live imaging to monitor mitochondrial segregation in individual progenitors and track their progeny’s fate within embryonic neural tissue, we show that daughter cells inheriting fewer mitochondria consistently differentiate into neurons, whereas their sibling receiving more mitochondria retains the progenitor status. Furthermore, experimental displacement of mitochondria during mitosis to force their unequal inheritance was sufficient to drive premature neuronal differentiation. Our findings establish a direct causal relationship between unequal mitochondrial inheritance and the asymmetric fate of sister cellsin vivo, uncovering a key mechanism in neural development.
Projections between the globus pallidus externa and cortex span motor and non-motor regions
Authors: Ferenczi E. A. , Wang W. , Biswas A. , Pottala T. , Dong Y. , Chan A. K. , Albanese M. A. , Sohur R. S. , Jia T. , Mastro K.J. , Sabatini B. L. 
Published: November 2024

AbstractThe globus pallidus externa (GPe) is a heterogenous nucleus of the basal ganglia, with intricate connections to other basal ganglia nuclei, as well as direct connections to the cortex. The anatomic, molecular and electrophysiologic properties of cortex-projecting pallidocortical neurons are not well characterized. Here we show that pallidocortical neurons project to diverse motor and non-motor cortical regions, are organized topographically in the GPe, and segregate into two distinct electrophysiological and molecular phenotypes. In addition, we find that the GPe receives direct synaptic input back from deep layers of diverse motor and non-motor cortical regions, some of which form reciprocal connections onto pallidocortical neurons. These results demonstrate the existence of a fast, closed-loop circuit between the GPe and the cortex which is ideally positioned to integrate information about behavioral goals, internal states, and environmental cues to rapidly modulate behavior.
Challenges in inferring breathing rhythms from olfactory bulb local field potentials
Authors: Rafilson Sidney E. , Hess Nathan , Findley Teresa M. , Smear Matthew C. 
Published: November 2024

AbstractOdors convey useful navigational and episodic information, yet much of the chemical world remains inaccessible without active sampling through sniffing. To effectively interpret olfactory cues, the brain must unify odor-driven activity with respiratory cycles, making accurate respiratory measurements critical in understanding olfactory bulb (OB) dynamics. Previous studies have shown that behavioral signals are often present in primary sensory areas, and OB local field potentials (LFPs) have long been known to couple with respiration. Here we investigated whether OB LFPs can reliably recover the precise timing and frequency of respiration. Our results indicate that OB LFPs across multiple frequency bands align with respiratory cycles. Using time and frequency domain methods, we show that 2-12 Hz LFP oscillations effectively track respiratory frequency. However, a monotonic relationship between LFP-respiratory delay and sniffing frequency, which varies across animals, renders the recovery of precise respiratory events challenging. This work demonstrates the complex and individualized relationship between rodent respiration and OB LFPs, contributing to our understanding of how respiratory signals are represented in the OB.
Medial prefrontal cortical neurotransmitters reactive to relapse-promoting and relapse-suppressing cues in rats trained to self-administer cocaine or alcohol
Authors: Nedelescu Hermina , Miliano Cristina , Wagner Grant E. , Kerr Tony M. , Gregus Ann M. , Weiss Friedbert , Buczynski Matthew W. , Suto Nobuyoshi 
Published: November 2024

ABSTRACTEnvironmental cues conditioned to signal drug availability (S+) or omission (S-) activate specific neurons (neuronal ensembles/engram cells) within the medial prefrontal cortex (mPFC) to promote and suppress drug relapse in rats. However, the neurochemical source of such cue-specific activation remains unknown. In this study, we determined extracellular neurotransmitter fluctuations reactive to S+ vs. S- in the infralimbic (IL) and prelimbic (PL) cortices of male rats trained to lever-press for cocaine or alcohol self-administration. In cocaine- or alcohol-trained rats exposed to S+, no significant neurotransmitter fluctuations were observed in IL or PL. In cocaine-trained rats exposed to S-, glutamate, serotonin, taurine and adenosine were increased in PL but not in IL. In alcohol-trained rats exposed to S-, glutamate was increased, while dopamine and GABA were decreased, in IL but not in PL. Although S+ reactive neurotransmitters driving neuronal activation in mPFC remains to be elucidated, glutamate is likely the source of such activation by S- in rats trained to self-administer cocaine or alcohol. While drugs used for self-administration and cue-conditioning appear to dictate the type and anatomical specificity of S- evoked neurotransmission within mPFC, glutamate may serve as a common therapeutic target to mimic relapse-suppression by S- across cocaine and alcohol use disorders (CUD and AUD). In contrast, serotonin, taurine and adenosine may serve as the targets in CUD, while dopamine and GABA may serve as the targets in AUD.
Taxes under stress: bank stress tests and corporate tax planning
Authors: Francis Bill B. , García Raffi E. , Harithsa Jyothsna G. 
Published: November 2024

PurposeThis paper aims to examine how bank stress tests affect bank tax planning.Design/methodology/approachThe study uses US bank stress test bank size thresholds and a regression discontinuity design to investigate the effect of the Dodd-Frank Act and the instituted bank stress tests on bank tax planning. We use different measures of tax planning, including bank-specific measures and measures of tax avoidance, tax aggressiveness, and effective tax planning from recent literature. Our regression discontinuity and difference-in-differences regression analyses include bank and year fixed-effects and lagged bank characteristics to control for potential endogeneity.FindingsThis study finds that stress tests have the unintended consequences of intensifying tax planning and increasing tax avoidance. Stress-test banks increase tax avoidance by accelerating charge-offs, net interest, and non-interest expenses. However, this increase in tax planning is not optimally maximized, leading to lower effective tax planning compared to non-stress-test banks. Banks with a substantial increase in tax avoidance under the Dodd–Frank Act tend to increase their risk, investing in high-risk-weight assets and lending in riskier loan categories. These findings are consistent with tax minimization conditions under added regulatory attention and policy uncertainty.Originality/valueLiterature on bank tax planning is limited. Most tax avoidance literature excludes financial institutions such as bank holding companies mainly due to differences in business practices and regulatory frameworks. This study is the first to investigate tax planning behavior among US banks. The current study thus extends the research field by examining the effect of bank transparency regulations, such as bank stress tests, on bank tax planning activities. Our findings have a direct bank policy implication. They show that stress testing has the unintended consequences of increasing tax planning activities and consequently increasing risk-taking on banks with high tax avoidance, which goes against the goals of stress testing regulations.
Construction logistics status and actors’ opinions – an industry wide survey in Sweden
Authors: Fredriksson Anna , Sezer Ahmet Anil , Sundquist Viktoria 
Published: November 2024

Purpose
The purpose of this paper is to investigate whether construction logistics services are still carried out mostly in an ad hoc manner, or has advanced to a more standardized, strategically implemented practice and to explore different actors’ attitudes towards construction logistics.

Design/methodology/approach
Unlike previous studies of construction logistics, relying on single or multiple case studies, a survey was designed to deliver a generalizable snapshot of contemporary industry practices and the status of construction logistics. A total of 902 responses from the Swedish construction industry were collected with the help of the industry wide questionnaire.

Findings
The results show that construction logistics setups (CLSs) are only used by 14% of the responding organizations, which confirms that construction logistics services are still mostly carried out in an ad hoc manner. This may change considering that respondents with more experience in the industry claim an increased demand for CLSs. The ad hoc approach is less common among contractors than other types of organizations and large organizations. Furthermore, there is a more positive attitude towards the benefits of construction logistics among the respondents from organizations having a standard CLS.

Originality/value
This is the first industry wide survey presenting the status of implementation level of standardized logistics services in the construction industry and the attitudes among industry actors towards logistics.
Unlocking the buffering role of total quality management: how organisational intangible resources shape innovation performance in dynamic and uncertain environments
Authors: Koomson Samuel 
Published: November 2024

Purpose
The purpose of this paper is to demonstrate how total quality management (TQM) buffers the adverse effect of market dynamism (MKD) on banking industry innovation performance (INP) using resource-based theory.

Design/methodology/approach
This paper creates and explores a conceptual framework by evaluating the perspectives of 260 chief executive officers from the different branches of 21 ISO 27001 and PCI-DSS-accredited banks over two time periods. The product indicator approach was used in the moderation analysis, with a path being significant at 5% (t > 1.96). The study used support for innovation, innovative leadership, strategic agility and slack resources as control variables for INP. The analysis was done using SmartPLS version 4.1.0.6.

Findings
As hypothesised, MKD had a significant and negative influence on the INP (ß = −0.326, t = 5.341). TQM neutralised MKD’s negative impacts on INP in a positive and significant manner (ß = 0.127, t = 2.680).

Research limitations/implications
This study paves the way for upcoming research to explore how TQM may improve INP in the presence of other adverse environmental dynamics like technological dynamism, competitive intensity and government regulation in the banking industry. External trends may have a different impact on other industries, necessitating additional research in these areas.

Practical implications
Bank managers can manipulate the TQM strategy to shape INP, thereby revealing TQM’s strategic value. Top management teams may consider prioritising and allocating more resources to TQM initiatives. Banks that successfully use the TQM methodology are able to turn a dynamic and uncertain environment into opportunities for growth and differentiation.

Originality/value
To the best of the author’s knowledge, this is the first study to display how TQM buffers the detrimental impact of MKD on INP. It offers a first attempt at challenging previous studies that had somewhat assumed that MKD encourages banks to be innovative, proving them otherwise, changing the narrative of the literature and stimulating further debate.