bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methods for assessing bee foraging preferences: a short review and a new automated apparatus
Authors: Magner Evin T. , Norris Jeff T. , Snell-Rood Emilie C. , Hegeman Adrian D. , Carter Clay J. 
Published: December 2023

ABSTRACTBees are essential pollinators for many plant species, but multiple threats exist to both managed and wild bee populations. Their innate foraging behaviors and food preferences are subjects of intense research since bee nutrition is essential for maintaining hive and colony health. Multiple approaches have been developed to assess bee foraging behavior and associated preferences, but they are often labor-intensive and provide data on a limited number of parameters. In this manuscript, we provide a short review of these methods and present the design, build, and implementation of a new, inexpensive, and automated feeding apparatus capable of recording: (1) number of visits, (2) total food consumed, (3) photos and videos of bee behavior while inside of the feeder, and (4) environmental conditions. The efficacy of this apparatus is demonstrated through preference tests with artificial nectars, while also acknowledging the relative strengths and limitations of this approach.
DeepPBS: Geometric deep learning for interpretable prediction of protein–DNA binding specificity
Authors: Mitra Raktim , Li Jinsen , Sagendorf Jared M. , Jiang Yibei , Chiu Tsu-Pei , Rohs Remo 
Published: December 2023

AbstractPredicting specificity in protein-DNA interactions is a challenging yet essential task for understanding gene regulation. Here, we present Deep Predictor of Binding Specificity (DeepPBS), a geometric deep-learning model designed to predict binding specificity across protein families based on protein-DNA structures. The DeepPBS architecture allows investigation of different family-specific recognition patterns. DeepPBS can be applied to predicted structures, and can aid in the modeling of protein-DNA complexes. DeepPBS is interpretable and can be used to calculate protein heavy atom-level importance scores, demonstrated as a case-study on p53-DNA interface. When aggregated at the protein residue level, these scores conform well with alanine scanning mutagenesis experimental data. The inference time for DeepPBS is sufficiently fast for analyzing simulation trajectories, as demonstrated on a molecular-dynamics simulation of aDrosophilaHox-DNA tertiary complex with its cofactor. DeepPBS and its corresponding data resources offer a foundation for machine-aided protein-DNA interaction studies, guiding experimental choices and complex design, as well as advancing our understanding of molecular interactions.
Epigenetic disruption of the RARγ complex impairs its function to bookmark AR enhancer interactions required for enzalutamide sensitivity in prostate cancer
Authors: Wani Sajad A , Hussain Shahid , Gray Jaimie S , Nayak Debasis , Tang Hancong , Perez Lillian M , Long Mark D , Siddappa Manjunath , McCabe Christopher J , Sucheston-Campbell Lara E , Freeman Michael R , Campbell Moray J 
Published: December 2023

ABSTRACTThe current study in prostate cancer (PCa) focused on the genomic mechanisms at the cross-roads of pro-differentiation signals and the emergence of lineage plasticity. We explored an understudied cistromic mechanism involving RARγ’s ability to govern AR cistrome-transcriptome relationships, including those associated with more aggressive PCa features. The RARγ complex in PCa cell models was enriched for canonical cofactors, as well as proteins involved in RNA processing and bookmarking. Identifying the repertoire of miR-96 bound and regulated gene targets, including those recognition elements marked by m6A, revealed their significant enrichment in the RARγ complex. RARγ significantly enhanced the AR cistrome, particularly in active enhancers and super-enhancers, and overlapped with the binding of bookmarking factors. Furthermore, RARγ expression led to nucleosome-free chromatin enriched with H3K27ac, and significantly enhanced the AR cistrome in G2/M cells. RARγ functions also antagonized the transcriptional actions of the lineage master regulator ONECUT2. Similarly, gene programs regulated by either miR-96 or antagonized by RARγ were enriched in alternative lineages and more aggressive PCa phenotypes. Together these findings reveal an under-investigated role for RARγ, modulated by miR-96, to bookmark enhancer sites during mitosis. These sites are required by the AR to promote transcriptional competence, and emphasize luminal differentiation, while antagonizing ONECUT2.
Neuropeptide Modulation of Bidirectional Internetwork Synapses
Authors: Fahoum Savanna-Rae H , Blitz Dawn M 
Published: December 2023

AbstractOscillatory networks underlying rhythmic motor behaviors, and sensory and complex neural processing, are flexible, even in their neuronal composition. Neuromodulatory inputs enable neurons to switch participation between networks, or participate in multiple networks simultaneously. Neuromodulation of internetwork synapses can both recruit and coordinate a switching neuron in a second network. We previously identified an example in which a neuron is recruited into dual-network activity via peptidergic modulation of intrinsic properties. We now ask whether the same neuropeptide also modulates internetwork synapses for internetwork coordination. The crab (Cancer borealis) stomatogastric nervous system contains two well-defined feeding-related networks (pyloric, food filtering, ∼1 Hz; gastric mill, food chewing, ∼0.1 Hz). The projection neuron MCN5 uses the neuropeptide Gly1-SIFamide to recruit the pyloric-only LPG neuron into dual pyloric plus gastric mill-timed bursting via modulation of LPG’s intrinsic properties. Descending input is not required for a coordinated rhythm, thus intra-network synapses between LPG and its second network must underlie coordination among these neurons. However, synapses between LPG and gastric mill neurons have not been documented. Using two-electrode voltage clamp recordings, we found that graded synaptic currents between LPG and gastric mill neurons (LG, IC, DG) were primarily negligible in saline, but were enhanced by Gly1-SIFamide. Further, LPG and gastric mill neurons entrain each other during Gly1-SIFamide application, indicating bidirectional, functional connectivity. Thus, a neuropeptide mediates neuronal switching through parallel actions, modulating intrinsic properties in a switching neuron to recruit it into a second network and as shown here, also modulating bidirectional internetwork synapses for coordination.New and NoteworthyNeuromodulation can enable neurons to be simultaneously coordinated with separate networks. Both recruitment into, and coordination with, a second network can occur via modulation of internetwork synapses. Alternatively, recruitment can occur via modulation of intrinsic ionic currents. We find that the same neuropeptide previously determined to modulate intrinsic currents also modulates bidirectional internetwork synapses that are typically ineffective. Thus, complementary modulatory peptide actions enable recruitment and coordination of a neuron into a second network.
Fully Automated Explainable Abdominal CT Contrast Media Phase Classification Using Organ Segmentation and Machine Learning
Authors: Salimi Yazdan , Mansouri Zahra , Hajianfar Ghasem , Sanaat Amirhossein , Shiri Isaac , Zaidi Habib 
Published: December 2023

AbstractPurposeTo detect contrast media injection phase from CT images by means of organ segmentation and deep learning.Materials and MethodsA total number of 2509 CT images split into four subsets of non-contrast (class #0), arterial (class #1), venous (class #2), and delayed (class #3) after contrast media injection were collected from two CT scanners. Seven organs including the liver, spleen, heart, kidneys, lungs, urinary bladder, and aorta along with body contour masks were generated by pre-trained deep learning algorithms. Subsequently, five first-order statistical features including average, standard deviation, 10, 50, and 90 percentiles extracted from the above-mentioned masks were fed to machine learning models after feature selection and reduction to classify the CT images in one of four above mentioned classes. A ten-fold data split strategy was followed. The performance of our methodology was evaluated in terms of classification accuracy metrics.ResultsThe best performance was achieved by Boruta feature selection and RF model with average area under the curve of more than 0.999 and accuracy of 0.9936 averaged over four classes and ten folds. Boruta feature selection selected all predictor features. The lowest classification was observed for class #2 (0.9888), which is already an excellent result. In the ten-fold strategy, only 33 cases from 2509 cases (∼1.4%) were misclassified.ConclusionWe developed a fast, accurate, reliable, and explainable methodology to classify contrast media phases which may be useful in data curation and annotation in big online datasets or local datasets with non-standard or no series description.Key pointsThe lack of standard series description and information about contrast media phase limits the usability of medical CT data.We developed a twostep deep learning/machine learning solution with excellent performance.This fast, automated, reliable and explainable purposed pipeline can tag every CT images with using only image matrices.
Copper-deficiency is associated with impairments in social behavior and oligodendrocyte development via mTOR signaling pathway
Authors: Usui Noriyoshi , Doi Miyuki , Berto Stefano , Matsuoka Kiwamu , Ishida Rio , Irie Koichiro , Nakama Nanako , Miyauchi Hana , Fujiwara Yuuki , Yamauchi Takahira , Hirai Takaharu , Toritsuka Michihiro , Xie Min-Jue , Kayashima Yoshinori , Umeda Naoko , Iwata Keiko , Okumura Kazuki , Harada Taeko , Yoshimura Takeshi , Katayama Taiichi , Tsujii Masatsugu , Matsuzaki Hideo , Makinodan Manabu , Shimada Shoichi 
Published: December 2023

AbstractAutism spectrum disorder (ASD) is a heterogeneous disorder characterized by impaired social communication and restricted repetitive behaviors, however the biological mechanisms remain unclear. Although trace elements play essential roles in the living body, it is unclear how alterations of trace elements in ASD are involved in pathogenesis. Here we analyzed the plasma metallome and identified the alterations of 11 elements in individuals with ASD. The copper decrease was negatively correlated with ASD symptom scores. A copper-deficient mouse model reflecting the condition showed ASD-like behaviors and impaired oligodendrocyte development. In copper-deficient mice, mechanistic target of rapamycin (mTOR) signaling was reduced, and its activation by agonist improved social impairment and oligodendrocyte developmental defects. Supporting these results, white matter volumes were negatively correlated with social symptoms in individuals with ASD. Our results demonstrate that copper-deficiency contributes to ASD by causing oligodendrocytes impairment via mTOR signaling. Our findings indicate that the effects of copper-deficiency and mTOR imbalance are relevant to the pathogenesis of ASD and are potential therapeutic targets.
Factors influencing referral to maternity models of care in Australian general practice
Authors: Thomas J , Kuliukas L , Frayne J , Bradfield Z 
Published: December 2023

AbstractBackgroundIn the Australian maternity system, general practitioners play a vital role in advising and directing prospective parents to maternity models of care. Optimising model of care discussions and the decision-making process avoids misaligning women with over or under specialised care, reduces the potential for disruptive care transitions and unnecessary healthcare costs, and is critical in ensuring consumer satisfaction. Current literature overwhelmingly focusses on women’s decision-making around model of care discussions and neglects the gatekeeping role of the General Practitioner (GP). This study aimed to explore and describe the factors influencing Australian GPs decision-making when referring pregnant women to maternity models of care.MethodsThis study used a qualitative descriptive approach. General practitioners (N=12) with experience referring women to maternity models of care in Australia participated in a semi-structured interview. Interviews occurred between October and November 2021 by telephone or videoconference. Reflexive thematic analysis was facilitated by NVivo-12 data management software to codify and interpret themes from the data.FindingsTwo broad themes were interpreted from the data. The first theme entitled ‘GP Factors’, incorporated three associated sub-themes including ‘GPs Previous Model of Care Experience’, ‘Gaps in GP Knowledge’ and ‘GP Perception of Models of Care’. The second theme, entitled ‘Woman’s Factors’, encapsulated two associated sub-themes including the ‘Woman’s Preferences’ and ‘Access to Models’.ConclusionsThis study provides novel evidence regarding general practitioner perspectives of the factors influencing model of care decision-making and referral. The exploration and description of factors influencing model of care decisions provide unique insight into the ways that all stakeholders can experience access to a broader range of models of care including midwifery-led continuity of care models aligned with consumer-demand. In addition, the role of national primary health networks is outlined as a means to achieving this.
The Philosophical Perspective in Transculturizing Instrument Tools to Detect Diabetic Foot Ulcer : A Literature Review
Authors: Awaluddin Sri Wahyuni , Rumambo Pandin Moses Glorino , Nursalam  
Published: December 2023

AbstractDiabetes foot ulcer (DFU) is one of the main complications of diabetes mellitus (DM) and one of the main causes of death worldwide from non-communicable diseases (NCDs). The development of an instrument tool for the early diagnosis of diabetic foot is crucial since the findings can be used to prioritize clinical examinations for patients who are at risk. This literature review aimed to examine the philosophical viewpoint on transculturalizing instrument instruments to detect DFU from a variety of study reports published in both domestic and foreign journals. The original research publications published between January 2018 and December 2023 were the focus of the literature search. This study used secondary data, which came from 17 credible journal publications obtained from Science Direct, CINAHL, Pubmed, and SCOPUS databases. The PICOS framework was utilized to assess the papers’ suitability after they were selected. Articles meeting the inclusion requirements would be chosen: the studies should show the outcome of DFU detection or intervention for the outcome, and the population should consist of DM patients with or without DFU, with early DFU detection or intervention for Intervention. The studies could use any kind of research design, including descriptive, cross-sectional, observational, quasi-experimental, randomized controlled trials, and mixed methods, and should be written in English. The result of this literature review showed all the newly developed instrument tools to detect DFU have tested the validity and reliability of content, particularly translation to the local language to meet cultural appropriateness. It is important for researchers working on new DFU detection risk tools to consider including transcultural theory in their assessment instruments for DFU early detection.
Cardiac afferent signals can facilitate visual dominance in binocular rivalry
Authors: Veillette John P. , Gao Fan , Nusbaum Howard C. 
Published: December 2023

AbstractSensory signals from the body’s visceral organs (e.g. the heart) can robustly influence the perception of exteroceptive sensations. This interoceptive-exteroceptive interaction has been argued to underlie self-awareness by situating one’s perceptual awareness of exteroceptive stimuli in the context of one’s internal state, but studies probing cardiac influences on visual awareness have yielded conflicting findings. In this study, we presented separate grating stimuli to each of subjects’ eyes as in a classic binocular rivalry paradigm – measuring the duration for which each stimulus dominates in perception. However, we caused the gratings to “pulse” at specific times relative to subjects’ real-time electrocardiogram, manipulating whether pulses occurred during cardiac systole, when baroreceptors signal to the brain that the heart has contracted, or in diastole when baroreceptors are silent. The influential “Baroreceptor Hypothesis” predicts the effect of baroreceptive input on visual perception should be uniformly suppressive. In contrast, we observed that dominance durations increased for systole-entrained stimuli, inconsistent with the Baroreceptor Hypothesis. Further, we show that this cardiac-dependent rivalry effect is preserved in subjects who are at-chance discriminating between systole-entrained and diastole-presented stimuli in a separate interoceptive awareness task, suggesting that our results are not dependent on conscious access to heartbeat sensations.
Differential spatial regulation and activation of integrin nanoclusters inside focal adhesions
Authors: Keary Sarah , Mateos Nicolas , Campelo Felix , Garcia-Parajo Maria F. 
Published: December 2023

Abstractα5β1and αvβ3integrins are core components of focal adhesions (FAs) involved in cell attachment, migration and mechanobiology-dependent processes. Recent works indicate that both integrins organize in nanoclusters inside FAs, with sub-populations of active and inactive β1nanoclusters. However, whether both integrins work in concert or their activities are spatially regulated is not fully understood. Using dual-color super-resolution microscopy we show that integrins α5β1and αvβ3exhibit similar functional nanoscale segregation. Notably, both integrins never mix at the nanoscale indicating that their functions might be spatially regulated. We find a nearly 1:1 stoichiometry between active integrin and adaptor nanoclusters suggesting that coordinated integrin activation occurs via the concurrent engagement of adaptor nanoclusters. Interestingly, α5β1nanoclusters preferentially localize at the FA periphery in close proximity to adaptor nanoclusters, establishing regions of multi-nanocluster enrichment, whereas αvβ3nanoclusters uniformly distribute throughout FAs. Overall, our results show that adhesion proteins arrange as modular nanoscale units that distinctively organize inside FAs to spatially regulate integrin activation and function.
An ancient transcription activator is required for the multiciliogenesis program
Authors: Jiang Haochen , Hua Mengting , Ding Mei , Hu Jiaqi , Zheng Shiqiong , Wang Hanchen , Wang Weihua , Xu Cheng , Xing Junqiao , Liu Hongni , Zhao Xue , Hu Zhangfeng 
Published: December 2023

AbstractMulticiliogenesis is an evolutionarily conserved process required a unique transcriptional program. The mechanisms governing multiciliogenesis are incompletely understood. Here we show that an ancient transcription activator, Edf1, is essential for the multiciliogenesis program. Mice lacking Edf1 exhibit postnatal hydrocephalus and delayed multiciliated cells (MCCs) differentiation. Functional studies reveal that MCCs in Edf1-/-mice have defects in tissue-level polarity and reduced motility. These defects result in abnormal cerebrospinal fluid (CSF) dynamics in vivo, potentially contributing to the development of hydrocephalus. Intriguingly, we found that the expression of pivotal ciliary transcription factors was decreased in Edf1-/-mice. Collectively, our data suggest that Edf1 modulates the multiciliogenesis by regulating the transcription of important ciliary transcription factors required for ciliary gene expression.
Interferon α and β induce differential transcriptional and functional metabolic phenotypes in human monocyte-derived macrophages and blunt glycolysis in response to antigenic stimuli
Authors: Leisching Gina , Yennemadi Anjali , Gogan Karl , Keane Joseph 
Published: December 2023

AbstractIn the context of acute settings, the roles of type I interferons (IFNs), notably subtypes IFNα2a, 2b, and β, in modulating macrophage metabolism and contributing to host defense against viral and bacterial pathogens are well-established. However, the impact of chronic exposure to type I IFNs on macrophage metabolism, intimately linked to macrophage function, remains less understood. This study aimed to unravel the nuanced host responses induced by type I IFN cytokines, offering insights for potential therapeutic approaches in diseases associated with these cytokines.Employing a combination of transcriptional profiling and real-time functional analysis, we delineated the temporal evolution of metabolic reprogramming in response to chronic interferon exposure. Our results reveal distinct transcriptional metabolic profiles between macrophages chronically exposed to IFNα and IFNβ. Agilent Seahorse assays demonstrated that IFNβ significantly diminishes the oxygen consumption rate and glycolytic proton extrusion rate in macrophages. Conversely, IFNα2b decreased parameters of mitochondrial fitness and induced a shift towards glutamine oxidation.Assessing the ability of macrophages to induce glycolysis in response to antigenic stimuli (LPS and iH37Rv), we found that chronic exposure to all IFN subtypes limited glycolytic induction. This study addresses a critical oversight in the literature, where individual roles of IFN subtypes are frequently amalgamated and lack distinction. These findings not only provide novel insights into the divergent effects of interferon α2a, α2b, and β on macrophage metabolism but also highlight their potential implications for developing targeted therapeutic strategies. This is particularly relevant in autoimmune disorders where type I IFNs, particularly IFNα, play a central role. The observed metabolic quiescence induced by chronic IFN exposure underscores its significance in macrophage functionality and its potential contribution to the pathophysiology of autoimmune disorders and susceptibility to infection.
Observation of E-cadherin Adherens Junction Dynamics with Metal-Induced Energy Transfer Imaging and Spectroscopy
Authors: Chen Tao , Karedla Narain , Enderlein Jörg 
Published: December 2023

Epithelial cadherin (E-cad) mediated cell-cell junctions play a crucial role in the establishment and maintenance of tissues and organs. In this study, we employed metal-induced energy transfer imaging and spectroscopy to investigate variations in intermembrane distance during adhesion between two model membranes adorned with E-cad. By correlating the measured intermembrane distances with the distinct E-cad junction states, as determined by their crystal structures, we probed the dynamic behavior and diversity of E-cad junctions across different binding pathways.Our observations led to the identification of a transient intermediate state referred to as the X-dimeric state and enabled a detailed analysis of its kinetics. We discovered that the formation of the X-dimer leads to significant membrane displacement, subsequently impacting the formation of other X-dimers. These direct experimental insights into the subtle dynamics of E-cad-modified membranes and the resultant changes in intermembrane distance provide novel perspectives on the assembly of E-cad junctions between cells. This knowledge en-hances our comprehension of tissue and organ development and may serve as a foundation for the development of innovative therapeutic strategies for diseases linked to cell-cell adhesion abnormalities.Significance StatementIn this study, we employed metal-induced energy transfer (MIET) imaging and spectroscopy to track variations in intermembrane distance during the adhesion of two membranes mediated by epithelial cadherin. Leveraging the high spatial resolution of MIET, we explored the dynamics of cadherins across various binding pathways. Furthermore, we successfully captured a transient intermediate state known as the X-dimer and revealed its ability to communicate with other X-dimers through membrane displacement. These discoveries offer valuable mechanistic insights into the dynamics of cadherin junctions.