bluuebunny/crossref_metadata_2025 huggingface dataset:
Multicolor fluorescence microscopy for surgical guidance using a chip-scale imager with a low-NA fiber optic plate and a multi-bandpass interference filter
Authors: Roschelle Micah , Rabbani Rozhan , Papageorgiou Efthymios , Zhang Hui , Cooperberg Matthew , Stohr Bradley A. , Niknejad Ali , Anwar Mekhail
Published: October 2023

In curative-intent cancer surgery, intraoperative fluorescence imaging of both diseased and healthy tissue can help to ensure successful removal of all gross and microscopic disease with minimal damage to neighboring critical structures, such as nerves. Current fluorescence-guided surgery (FGS) systems, however, rely on bulky and rigid optics that incur performance-limiting trade-offs between sensitivity and maneuverability. Moreover, many FGS systems are incapable of multiplexed imaging. As a result, clinical FGS is currently limited to millimeter-scale detection of a single fluorescent target. Here we present a scalable, lens-less fluorescence imaging chip, VISION, capable of sensitive and multiplexed detection within a compact form factor. Central to VISION is a novel optical frontend design combining a low-numerical-aperture fiber optic plate (LNA-FOP) and a multi-bandpass interference filter, which is affixed to a custom CMOS image sensor. The LNA-FOP acts as a planar collimator to improve resolution and compensate for the angle-sensitivity of the interference filter, enabling high-resolution and multiplexed fluorescence imaging without lenses. We show VISION is capable of detecting tumor foci of less than 100 cells at near video framerates and, as proof of principle, can simultaneously visualize both tumor and nerves inex vivoprostate tissue.
Angiopoietin-like protein 2 mediates vasculopathy driven fibrogenesis in a mouse model of systemic sclerosis
Authors: Saha Dyuti , Thannimangalath Sujaya , Pincha Neha , Kiran Ravi , Hegde Akshay , Kataria Sunny , Dam Binita , Hiwale Ankita , Ravula Venkatesh , Rahulan Lekshmi Minikumari , Nigam Neha , Singh Neha , Agarwal Vikas , Vemula Praveen K. , Jamora Colin
Published: October 2023

Vasculopathy is a common hallmark of various fibrotic disorders including systemic sclerosis (SSc), yet its underlying etiology and contribution to fibrogenesis remain ill-defined. In SSc the vasculopathy typically precedes the onset of fibrosis and we observed that this phenomenon is recapitulated in the Snail transgenic mouse model of SSc. The vascular anomalies manifest as deformed vessels, endothelial cell dysfunction and vascular leakage. Our investigation into the underlying mechanism of this phenotype revealed that Angiopoietin-like protein 2 (Angptl2), secreted by the Snail transgenic keratinocytes, is a principal driver of fibrotic vasculopathy. In endothelial cells, Angptl2 upregulates pro-fibrotic genes, downregulates the tight junction protein Claudin 5, and prompts the acquisition of mesenchymal characteristics. Inhibiting endothelial cell junctional instability and consequently vascular leakage with a synthetic analog of the microbial metabolite Urolithin A (UAS03) effectively mitigated the vasculopathy and inhibited fibrogenesis. Thus, Angptl2 emerges as a promising early biomarker of the disease and inhibiting the vasculopathy inducing effects of this protein with agents such as UAS03 presents an appealing therapeutic avenue to reduce disease severity. These insights hold the potential to revolutionize the approach to the treatment of fibrotic diseases by targeting the vascular defects.
Instability in computational models of vascular smooth muscle cell contraction
Authors: Giudici Alessandro , Szafron Jason M , Ramachandra Abhay B , Spronck Bart
Published: October 2023

Purpose

Through their contractile and synthetic capacity, vascular smooth muscle cells play a key role in regulating the stiffness and resistance of the circulation. To model the contraction of blood vessels, an active stress component can be added to the (passive) Cauchy stress tensor. Different constitutive formulations have been proposed to describe this active stress component. Notably, however, theex vivomeasurement of the biomechanical behaviour of contacted blood vessels presents several experimental challenges, which complicate the acquisition of comprehensive data sets to inform complex active stress models. In this work, we examine formulations for use with limited experimental contraction data as well as those developed to capture more comprehensive data sets.

Methods

We prove analytically that a subset of these formulations exhibits unstable behaviours (i.e., a non-unique diameter solution for a given pressure) in certain parameter ranges, particularly when contractile deformations are large. Furthermore, using experimental literature data, we present two case studies where these active stress models are used to capture the contractile response of vascular smooth muscle cells in the presence of 1) limited and 2) extensive contraction data.

Results

Our work shows how limited contraction data complicates the selection of an appropriate active stress model for vascular applications, potentially resulting in unrealistic modelled behaviours.

Conclusion

As such, the data presented herein provide a useful reference for the selection of an active stress model which balances the trade-off between accuracy and the available biomechanical information.
Identification of the KIF18A alpha-4 helix as a therapeutic target for chromosomally unstable tumor cells
Authors: Schutt Katherine , Queen Katelyn A. , Fisher Kira , Budington Olivia , Mao Weifeng , Liu Wei , Xiao Yisong , Aswad Fred , Joseph James , Stumpff Jason
Published: October 2023

The mitotic kinesin, KIF18A, is required for proliferation of cancer cells that exhibit chromosome instability (CIN), implicating it as a promising target for treatment of a subset of aggressive tumor types. Determining regions of the KIF18A protein to target for inhibition will be important for the design and optimization of effective small molecule inhibitors. In this study, we investigated the effects of mutating S284 within the alpha-4 helix of KIF18A, which was previously identified as a phosphorylated residue. Mutations in S284 cause relocalization of KIF18A from the plus-ends of spindle microtubules to the spindle poles. Furthermore, KIF18A S284 mutants display loss of KIF18A function and fail to support proliferation in CIN tumor cells. Interestingly, similar effects on KIF18A localization and function were seen after treatment of CIN cells with KIF18A inhibitory compounds that are predicted to interact with residues within the alpha-4 helix. These data implicate the KIF18A alpha-4 helix as an effective target for inhibition and demonstrate that small molecules targeting KIF18A selectively limit CIN tumor cell proliferation and result in phenotypically similar effects on mitosis at the single cell level compared to genetic perturbations.
The fitness consequences of genetic divergence between polymorphic gene arrangements
Authors: Charlesworth Brian
Published: October 2023

Inversions restrict recombination when heterozygous with standard arrangements, but often have few noticeable phenotypic effects. Nevertheless, there are several examples of inversions that can be maintained polymorphic by strong selection under laboratory conditions. A long-standing model for the source of such selection is divergence between arrangements with respect to recessive or partially recessive deleterious mutations, resulting in a selective advantage to heterokaryotypic individuals over homokaryotypes. This paper uses a combination of analytical and numerical methods to investigate this model, for the simple case of an autosomal inversion with multiple independent nucleotide sites subject to deleterious mutations. A complete lack of recombination in heterokaryotypes is assumed, as well as constancy of the frequency of the inversion over space and time. It is shown that a significantly higher mutational load will develop for the less frequent arrangement. A selective advantage to heterokaryotypes is only expected when the two alternative arrangements are nearly equal in frequency, so that their mutational loads are very similar in size. The effects of someDrosophila pseudoobscurapolymorphic inversions on fitness traits seem to be too large to be explained by this process, although it may contribute to some of the observed effects. Several population genomic statistics can provide evidence for signatures of a reduced efficacy of selection associated with the rarer of two arrangements, but there is currently little published data that are relevant to the theoretical predictions.
Continuously fluctuating selection reveals extreme granularity and parallelism of adaptive tracking
Authors: Bitter M.C. , Berardi S. , Oken H. , Huynh A. , Schmidt P. , Petrov D.A.
Published: October 2023

Temporally fluctuating environmental conditions are a ubiquitous feature of natural habitats. Yet, how finely natural populations adaptively track fluctuating selection pressures via shifts in standing genetic variation is unknown. We generated high-frequency, genome-wide allele frequency data from a genetically diverse population ofDrosophila melanogasterin extensively replicated field mesocosms from late June to mid-December, a period of ∼12 generations. Adaptation throughout the fundamental ecological phases of population expansion, peak density, and collapse was underpinned by extremely rapid, parallel changes in genomic variation across replicates. Yet, the dominant direction of selection fluctuated repeatedly, even within each of these ecological phases. Comparing patterns of allele frequency change to an independent dataset procured from the same experimental system demonstrated that the targets of selection are predictable across years. In concert, our results reveal fitness-relevance of standing variation that is likely to be masked by inference approaches based on static population sampling, or insufficiently resolved time-series data. We propose such fine-scaled temporally fluctuating selection may be an important force maintaining functional genetic variation in natural populations and an important stochastic force affecting levels of standing genetic variation genome-wide.
Tripod transcranial alternating current stimulation at 5-Hz to alleviate anxiety symptoms: a preliminary report
Authors: Lee Tien-Wen , Li Chiang-Shan R. , Tramontano Gerald
Published: October 2023

Introduction

One of the most common applications of transcranial electrical stimulation (tES) at low current intensity is to induce a relaxed state or reduce anxiety. With technical advancement, different waveforms, montages, and parameters can be incorporated into the treatment regimen. We developed a novel protocol to treat individuals with anxiety disorders by transcranial alternating current stimulation (tACS).

Methods

A total of 27 individuals with anxiety disorders underwent tACS treatment for 12 sessions, with each session lasting 25 minutes. tACS at 5 Hz was applied to F4 (1.0 mA), P4 (1.0 mA), and T8 (2.0 mA) EEG lead positions (tripod), with sinewave oscillation between T8 and F4/P4. We evaluated the primary and secondary outcomes using the Beck Anxiety Inventory (BAI) and neuropsychological assessments.

Results

Of the 27 patients, 19 (70.4%) experienced a reduction in symptom severity greater than 50%, with an average reduction of BAI 58.5%. All reported side effects were mild, with itching or tingling being the most common complaint. No significant differences were noted in attention, linguistic working memory, visuospatial working memory, or long-term memory in neuropsychological assessments.

Conclusion

The results suggest the potential of this novel tripod tACS design as a rapid anxiety alleviator and the importance of a clinical trial to verify its efficacy.
GRAMD2+alveolar type I cell plasticity facilitates cell state transitions in organoid culture
Authors: Shen Hua , Chen Weimou , Liu Yixin , Castaldi Alessandra , Castillo Jonathan , Horie Masafumi , Flodby Per , Sundar Shivah , Li Changgong , Ji Yanbin , Minoo Parviz , Marconett Crystal N , Zhou Beiyun , Borok Zea
Published: October 2023

Alveolar epithelial regeneration is critical for normal lung function and becomes dysregulated in disease. While alveolar type 2 (AT2) and club cells are known distal lung epithelial progenitors, determining if alveolar epithelial type 1 (AT1) cells also contribute to alveolar regeneration has been hampered by lack of highly specific mouse models labeling AT1 cells. To address this, theGramd2CreERT2transgenic strain was generated and crossed toRosamTmGmice. Extensive cellular characterization, including distal lung immunofluorescence and cytospin staining, confirmed that GRAMD2+AT1 cells are highly enriched for green fluorescent protein (GFP). Interestingly,Gramd2CreERT2GFP+cells were able to form organoids in organoid co-culture with Mlg fibroblasts. Temporal scRNAseq revealed thatGramd2+AT1 cells transition through numerous intermediate lung epithelial cell states including basal, secretory and AT2 cell in organoids while acquiring proliferative capacity. Our results indicate thatGramd2+AT1 cells are highly plastic suggesting they may contribute to alveolar regeneration.
Encoding of melody in the human auditory cortex
Authors: Sankaran Narayan , Leonard Matthew K. , Theunissen Frederic , Chang Edward F.
Published: October 2023

Melody is a core component of music in which discrete pitches are serially arranged to convey emotion and meaning. Perception of melody varies along several pitch-based dimensions: (1) the absolute pitch of notes, (2) the difference in pitch between successive notes, and (3) the higher-order statistical expectation of each note conditioned on its prior context. While humans readily perceive melody, how these dimensions are collectively represented in the brain and whether their encoding is specialized for music remains unknown. Here, we recorded high-density neurophysiological activity directly from the surface of human auditory cortex while Western participants listened to Western musical phrases. Pitch, pitch-change, and expectation were selectively encoded at different cortical sites, indicating a spatial code for representing distinct dimensions of melody. The same participants listened to spoken English, and we compared evoked responses to music and speech. Cortical sites selective for music were systematically driven by the encoding of expectation. In contrast, sites that encoded pitch and pitch-change used the same neural code to represent equivalent properties of speech. These findings reveal the multidimensional nature of melody encoding, consisting of both music-specific and domain-general sound representations in auditory cortex.

Teaser

The human brain contains both general-purpose and music-specific neural populations for processing distinct attributes of melody.
Diabetes Diagnosis through Machine Learning: Investigating Algorithms and Data Augmentation for Class Imbalanced BRFSS Dataset
Authors: Chowdhury Mohammad Mihrab , Ayon Ragib Shahariar , Hossain Md Sakhawat
Published: October 2023

Diabetes is a prevalent chronic condition that poses significant challenges to early diagnosis and identifying at-risk individuals. Machine learning plays a crucial role in diabetes detection by leveraging its ability to process large volumes of data and identify complex patterns. However, imbalanced data, where the number of diabetic cases is substantially smaller than non-diabetic cases, complicates the identification of individuals with diabetes using machine learning algorithms. Our study focuses on predicting whether a person is at risk of diabetes, considering the individual’s health and socio-economic conditions while mitigating the challenges posed by imbalanced data. To minimize the impact of imbalance data, we employed several data augmentation techniques such as oversampling (SMOTE-N), undersampling (ENN), and hybrid sampling techniques (SMOTE-Tomek and SMOTE-ENN) on training data before applying machine learning algorithms. Our study sheds light on the significance of carefully utilizing data augmentation techniques, without any data leakage, in enhancing the effectiveness of machine learning algorithms. Moreover, it offers a complete machine learning structure for healthcare practitioners, from data obtaining to ML prediction, enabling them to make data-informed strategies.
Dynamic evaluation of spine kinematics in individuals with Parkinson’s disease and freezing of gait
Authors: Palmisano C. , Farinelli V. , Camuncoli F. , Favata A. , Pezzoli G. , Frigo C.A. , Isaias I.U.
Published: October 2023

Background

Freezing of gait (FoG) is an episodic failure of gait exposing people with Parkinson’s disease (PD) to a high risk of falling. Despite growing evidence of the interconnection between impaired trunk control and FoG, a detailed description of spinal kinematics during walking is still lacking in this population.

Research question

Do spinal alterations impact gait performance in individuals with PD and FoG?

Methods

We analyzed kinematic data of 47 PD participants suffering (PD-FOG, N=24) or not suffering from FoG (PD-NFOG, N=23) and 15 healthy controls (HCO) during quiet standing and unperturbed walking. We estimated the main spinal variables (i.e., spinal length, lordosis and kyphosis angles, trunk inclination), the pelvis angles, and the shoulder-pelvis angles during gait and standing. We studied differences across conditions and groups and the relationships between postural and gait parameters using linear regression methods.

Results

During standing and walking, both PD groups showed increased trunk inclination and decreased lordosis angle with respect to HCO, as well as a decreased range in variation of kyphosis angle, pelvic obliquity, and shoulder-pelvis angles. Only PD-FOG participants showed reduced range of lordosis angle and spinal length compared to HCO. PD-FOG individuals were also not able to straighten their spine during walking compared to standing. Stride length and velocity were decreased in both patient groups compared to HCO, while swing duration was reduced only in the PD-FOG group. In individuals with PD-FOG, trunk inclination and lordosis angle showed moderate but significant positive correlations with all gait alterations.

Significance

Spine alterations impacted gait performance in individuals with PD suffering from FoG. Excessive trunk inclination and poor mastering of the lordosis spinal region may create an unfavourable postural precondition for forward walking. Physical therapy should target combined spinal and stepping alterations in these individuals.
A proof-of-concept investigation into predicting follicular carcinoma on ultrasound using topological data analysis and radiomics
Authors: Thomas Andrew M , Lin Ann C , Deng Grace , Xu Yuchen , Ranvier Gustavo Fernandez , Taye Aida , Matteson David S , Lee Denise
Published: October 2023

Aims

Sonographic risk patterns identified in established risk stratification systems (RSS) may not accurately stratify follicular carcinoma from adenoma, which share many similar US characteristics. The purpose of this study is to investigate the performance of a multimodal machine learning model utilizing radiomics and topological data analysis (TDA) to predict malignancy in follicular thyroid neoplasms on ultrasound.

Methods

This is a retrospective study of patients who underwent thyroidectomy with pathology confirmed follicular adenoma or carcinoma at a single academic medical center between 2010–2022. Features derived from radiomics and TDA were calculated from processed ultrasound images and high-dimensional features in each modality were projected onto their first two principal components. Logistic regression with L2 penalty was used to predict malignancy and performance was evaluated using leave-one-out cross-validation and area under the curve (AUC).

Results

Patients with follicular adenomas (n=7) and follicular carcinomas (n=11) with available imaging were included. The best multimodal model achieved an AUC of 0.88 (95% CI: [0.85, 1]), whereas the best radiomics model achieved an AUC of 0.68 (95% CI: [0.61, 0.84]).

Conclusions

We demonstrate that inclusion of topological features yields strong improvement over radiomics-based features alone in the prediction of follicular carcinoma on ultrasound. Despite low volume data, the TDA features explicitly capture shape information that likely augments performance of the multimodal machine learning model. This approach suggests that a quantitative based US RSS may contribute to the preoperative prediction of follicular carcinoma.
Biomarkers of bleeding and venous thromboembolism in patients with acute leukemia
Authors: Hisada Yohei , Archibald Sierra J. , Bansal Karan , Chen Yanjun , Dai Chen , Dwarampudi Sindhu , Balas Nora , Hageman Lindsey , Key Nigel S. , Bhatia Smita , Bhatia Ravi , Mackman Nigel , Gangaraju Radhika
Published: October 2023

Background

Coagulopathy and associated bleeding and venous thromboembolism (VTE) are major causes of morbidity and mortality in patients with acute leukemia. The underlying mechanisms of these complications have not been fully elucidated.

Objectives

To evaluate the associations between biomarker levels and bleeding and VTE in acute leukemia patients.

Patients/Method

We examined plasma levels of activators, inhibitors and biomarkers of the coagulation and fibrinolytic pathways in patients ≥18 years with newly diagnosed acute leukemia compared to healthy controls. Multivariable regression models were used to examine the association of biomarkers with bleeding and VTE in acute leukemia patients. The study included 358 patients with acute leukemia (29 acute promyelocytic leukemia [APL], 253 non-APL acute myeloid leukemia [AML] and 76 acute lymphoblastic leukemia [ALL]), and 30 healthy controls.

Results

Patients with acute leukemia had higher levels of extracellular vesicle (EV) tissue factor (TF) activity, phosphatidylserine-positive EVs, plasminogen activator inhibitor-1 (PAI-1), plasmin-antiplasmin complexes, cell-free DNA and lower levels of citrullinated histone H3-DNA complexes compared to healthy controls. APL patients had the highest levels of EVTF activity and the lowest levels of tissue plasminogen activator among the acute leukemia patients. There were 41 bleeding and 37 VTE events in acute leukemia patients. High EVTF activity was associated with increased risk of bleeding (sHR 2.30, 95%CI 0.99-5.31) whereas high PAI-1 was associated with increased risk of VTE (sHR 3.79, 95%CI 1.40-10.28) in these patients.

Conclusions

Our study shows alterations in several biomarkers in acute leukemia and identifies biomarkers associated with risk of bleeding and VTE.

Essentials

The mechanisms of acute leukemia-associated bleeding and thrombosis have not been elucidated.

We measured plasma biomarkers of coagulation and fibrinolysis in acute leukemia patients.

Biomarkers of the coagulation and fibrinolytic pathways are altered in acute leukemia patients.

EVTF activity is associated with bleeding, and PAI-1 is associated with VTE in acute leukemia.
Theta and alpha oscillations in human hippocampus and medial parietal cortex support the formation of location-based representations
Authors: Satish Akul , Keller Vanessa G. , Raza Sumaiyah , Fitzpatrick Shona , Horner Aidan J.
Published: October 2023

Our ability to navigate in a new environment depends on learning new locations. Mental representations of locations are quickly accessible during navigation and allow us to know where we are regardless of our current viewpoint. Recent fMRI research using pattern classification has shown that these location-based representations emerge in the retrosplenial cortex and parahippocampal gyrus, regions theorised to be critically involved in spatial navigation. However, little is currently known about the oscillatory dynamics that support the formation of location-based representations. We used MEG to investigate region-specific oscillatory activity in a task where participants could form location-based representations. Participants viewed videos showing that two perceptually distinct scenes (180° apart) belonged to the same location. This “overlap” video allowed participants to bind the two distinct scenes together into a more coherent location-based representation. Participants also viewed control “non-overlap” videos where two distinct scenes from two different locations were shown, where no location-based representation could be formed. In a post-video behavioural task, participants successfully matched the two viewpoints shown in the overlap videos, but not the non-overlap videos, indicating they successfully learned the locations in the overlap condition. Comparing oscillatory activity between the overlap and non-overlap videos, we found greater theta and alpha/beta power during the overlap relative to non-overlap videos, specifically at time-points when we expected scene integration to occur. These oscillations localised to regions in the medial parietal cortex (precuneus and retrosplenial cortex) and the medial temporal lobe, including the hippocampus. Therefore, we find that theta and alpha/beta oscillations in the hippocampus and medial parietal cortex are likely involved in the formation of location-based representations.
DynaMight: estimating molecular motions with improved reconstruction from cryo-EM images
Authors: Schwab Johannes , Kimanius Dari , Burt Alister , Dendooven Tom , Scheres Sjors H.W.
Published: October 2023

How to deal with continuously flexing molecules is one of the biggest outstanding challenges in single-particle analysis of proteins from cryo-EM images. Here, we present DynaMight, a new software tool that estimates a continuous space of conformations in a cryo-EM data set by learning 3D deformations of a Gaussian pseudo-atomic model of a consensus structure for every particle image. Inversion of the learnt deformations is then used to obtain an improved reconstruction of the consensus structure. We illustrate the performance of DynaMight for several experimental cryo-EM data sets. We also show how error estimates on the deformations may be obtained by independently training two variational autoencoders (VAEs) on half sets of the cryo-EM data, and how regularisation of the 3D deformations through the use of atomic models may lead to important artefacts due to model bias. DynaMight is distributed as free, open-source software, as part of RELION-5.
Stress-induced nucleoid remodeling inDeinococcus radioduransis associated with major changes in HU abundance and dynamics
Authors: Vauclare Pierre , Wulffelé Jip , Lacroix Françoise , Servant Pascale , Confalonieri Fabrice , Kleman Jean-Philippe , Bourgeois Dominique , Timmins Joanna
Published: October 2023

Bacteria have developed a wide range of strategies to respond to stress, one of which is the rapid large-scale reorganization of their nucleoid, which is often associated with a major reprogramming of the gene expression profile. Nucleoid associated proteins (NAPs) are believed to be major actors in this process, but the molecular mechanisms underlying stress-induced nucleoid remodeling remain poorly understood. Here, using the radiation resistant bacterium,D. radiodurans, as a model, and advanced fluorescence microscopy approaches, we examined the changes in nucleoid morphology and compaction induced by either entry into stationary phase or exposure to UV-C light, and characterized the associated changes in abundance and dynamics of the major NAP inD. radiodurans, the heat-unstable (HU) protein. While both types of stress induced a similar macroscopic rearrangement of the nucleoid into a more compact structure, HU diffusion was significantly reduced in stationary phase cells, but was instead dramatically increased following exposure to UV-C, suggesting that the underlying mechanisms of remodeling are distinct. Furthermore, a detailed comparison of the cellular response to sublethal and lethal doses of UV-C light revealed that UV-induced nucleoid remodeling involves a rapid nucleoid condensation step associated with increased HU diffusion and abundance, followed by a slower decompaction phase to restore normal nucleoid morphology and HU dynamics, before cell growth and division can resume. Together, these findings shed light on the diversity and complexity of stressed-induced nucleoid remodeling processes in bacteria.
UGGT1-mediated reglucosylation ofN-glycan competes with ER-associated degradation of unstable and misfolded glycoproteins
Authors: Ninagawa Satoshi , Matsuo Masaki , Ying Deng , Oshita Shuichiro , Aso Shinya , Matsushita Kazutoshi , Taniguchi Mai , Fueki Akane , Yamashiro Moe , Sugasawa Kaoru , Saito Shunsuke , Imami Koshi , Kizuka Yasuhiko , Sakuma Tetsushi , Yamamoto Takashi , Yagi Hirokazu , Kato Koichi , Mori Kazutoshi
Published: October 2023

How the fate (folding versus degradation) of glycoproteins is determined in the endoplasmic reticulum (ER) is an intriguing question. Monoglucosylated glycoproteins are recognized by lectin chaperones to facilitate their folding, whereas glycoproteins exposing well-trimmed mannoses are subjected to glycoprotein ER-associated degradation (gpERAD); we have elucidated how mannoses are sequentially trimmed by EDEM family members (George et al., 2020, 2021 eLife). Although reglucosylation by UGGT was previously reported to have no effect on substrate degradation, here we directly tested this notion using cells with genetically disrupted UGGT1/2. Strikingly, the results showed that UGGT1 delayed the degradation of misfolded substrates and unstable glycoproteins including ATF6α. An experiment with a point mutant of UGGT1 indicated that the glucosylation activity of UGGT1 was required for the inhibition of early glycoprotein degradation. These and overexpression-based competition experiments suggested that the fate of glycoproteins is determined by a tug-of-war between structure formation by UGGT1 and degradation by EDEMs. We further demonstrated the physiological importance of UGGT1, since ATF6α cannot function properly without UGGT1. Thus, our work strongly suggests that UGGT1 is a central factor in ER protein quality control via regulation of both glycoprotein folding and degradation.
ERα mediated gene state switching regulates the extent of the single-cell estrogen response
Authors: Day Christopher R. , Yasar Pelin , Adedoyin Gloria , Bennett Brian D. , Rodriguez Joseph
Published: October 2023

Gene regulation is complex, involving the coordination of hundreds of proteins that function to control genome accessibility, mediate enhancer-promoter interactions, and initiate transcription. At individual loci, transcriptional initiation is stochastic, resulting in short periods of nascent RNA synthesis known as transcriptional bursts. To understand how altered Estrogen Receptor function and cofactor recruitment regulates transcriptional bursting, we used single molecule imaging of estrogen responsive genes in Bisphenol A (BPA) treated cells. Using live cell imaging of the estrogen responsiveTFF1gene, we observe that cells treated with BPA exhibited burst initiation kinetics and burst sizes which were indistinguishable from cells induced with Estradiol (E2). However, we observed a 50% reduction in the number of active alleles in BPA treated cells. This effect is gene specific, asGREB1was unperturbed. Although we observed no difference in chromatin accessibility, theTFF1promoter exhibited an altered structure which coincided with reduced ERα and cofactor binding. Lastly, deletion of the enhancer locus removed the BPA effect, indicating that enhancer function was perturbed. Our results demonstrate gene specific effects of altered ERα recruitment and function which lead to a reduction of transcriptionally permissive states. Our work supports the model that the early estrogen response occurs from alleles in primed transcriptionally permissive states with additional inactive alleles contributing to the response over time.
Dose-dependent effects of histone methyltransferase NSD2 on site-specific double-strand break repair
Authors: Iwasaki Koh , Tojo Akari , Kobayashi Haruka , Kamimura Yoshitaka , Horikoshi Yasunori , Fukuto Atsuhiko , Sun Jiying , Yasui Manabu , Honma Masamitsu , Okabe Atsushi , Fujiki Ryoji , Kaneda Atsushi , Tashiro Satoshi , Sassa Akira , Ura Kiyoe
Published: October 2023

Histone modifications are catalyzed and recognized by specific proteins to regulate dynamic DNA metabolism processes. NSD2 is a histone H3 lysine 36 (H3K36)-specific methyltransferase that associates both with various transcription regulators and DNA repair factors. Specifically, it has been implicated in the repair of DNA double-strand breaks (DSBs); however, the role of NSD2 during DSB repair remains enigmatic. Here, we show that NSD2 does not accumulate at DSB sites and that the localization of NSD2 at chromatin is maintained even after DSB formation. Using three different DSB repair reporter systems, which contained the endonuclease site in the active thymidine kinase gene (TK) locus, we demonstrated separate dose-dependent effects of NSD2 on HR, canonical-NHEJ (c-NHEJ), and non-canonical-NHEJ (non-c-NHEJ). Endogenous NSD2 has a role in repressing non-c-NHEJ, without affecting DSB repair efficiency by HR or total NHEJ. Furthermore, overexpression of NSD2 promotes c-NHEJ repair suppressing HR repair. Therefore, we propose that NSD2 has functions in chromatin integrity at the active regions during DSB repair.
UPL3 Promotes BZR1 Degradation, Growth Arrest, and Seedling Survival under Starvation Stress inArabidopsis
Authors: Zhang Zhenzhen , Zhang Hongliang , Gonzalez Efren , Grismer Tarabryn , Xu Shou-Ling , Wang Zhi-Yong
Published: October 2023

BRASSINAZONE RESISTANT 1 (BZR1) is a key transcription factor of the brassinosteroid signaling pathway but also a signaling hub that integrates diverse signals that modulate plant growth. Previous studies have shown that starvation causes BZR1 degradation, but the underlying mechanisms are not understood. Here we performed quantitative proteomic analysis of BZR1 interactome under starvation conditions and identified two BZR1-interacting ubiquitin ligases, BAF1 and UPL3. Compared to the wild type, theupl3mutants show long hypocotyl and increased BZR1 levels when grown under sugar starvation conditions but not when grown on sugar-containing media, indicating a role of UPL3 in BZR1 degradation specifically under starvation conditions. Theupl3mutants showed a reduced survival rate after starvation treatment, supporting the importance of UPL3-mediated BZR1 degradation and growth arrest for starvation survival. Treatments with inhibitors of TARGET of RAPAMYCIN (TOR) and autophagy altered BZR1 level in the wild type but were less effective inupl3, suggesting that UPL3 mediates the TOR-regulated and autophagy-dependent degradation of BZR1. Further, the UPL3 protein level is increased posttranscriptionally by starvation but decreased by sugar treatment. Our study identifies UPL3 as a key component that mediates sugar regulation of hormone signaling pathways, important for optimal growth and survival in plants.

IN A NUTSHELL

Background

The coordination between signaling pathways that monitor the levels of photosynthate and growth hormones is crucial for optimizing growth and survival, but the underlying mechanisms are not fully understood. When the sugar level is low, the BZR1 transcription factor of the brassinosteroid (BR) signaling pathway is degraded, and hence growth is attenuated to prevent starvation and enhance survival. When sugar is sufficient, sugar signaling inhibits BZR1 degradation and enables BR promotion of plant growth. The key component that mediates starvation-induced BZR1 degradation remains unknown.

Question

What proteins interact with BZR1 and mediate its degradation under sugar starvation?

Finding

We performed immunoprecipitation mass spectrometry analysis of BZR1 in starvation-treated Arabidopsis and identified many BZR1-interacting proteins, including two E3 ligases UPL3 and BAF1. Genetic analysis showed that UPL3 plays a specific and prominent role in promoting autophagy-dependent BZR1 degradation and plant survival under sugar-starvation conditions.

Next step

How sugar-TOR signaling regulates UPL3 level remains to be studied in the future.
Modulation by NPYR underlies experience-dependent, sexually dimorphic learning
Authors: Peedikayil-Kurien Sonu , Haque Rizwanul , Gat Asaf , Oren-Suissa Meital
Published: October 2023

The evolutionary paths taken by each sex within a given species sometimes diverge, resulting in behavioral differences. Given their distinct needs, the mechanism by which each sex learns from a shared experience is still an open question. Here, we reveal sexual dimorphism in learning:C. elegansmales do not learn to avoid the pathogenic bacteria PA14 as efficiently and rapidly as hermaphrodites. Notably, neuronal activity following pathogen exposure was dimorphic: hermaphrodites generate robust representations, while males, in line with their behavior, exhibit contrasting representations. Transcriptomic and behavioral analysis revealed that the neuropeptide receptornpr-5, an ortholog of the mammalian NPY receptor, regulates male learning by modulating neuronal activity. Furthermore, we show the dependency of the males’ decision-making on their sexual status and demonstrate the pivotal role ofnpr-5as a modulator of incoming sensory cues. Taken together, we portray sex-specific plasticity in behavior toward a shared experience by modulating learning.
Small-angle scattering tensor tomography algorithm for robust reconstruction of complex textures
Authors: Nielsen Leonard C. , Erhart Paul , Guizar-Sicairos Manuel , Liebi Marianne
Published: October 2023

The development of small-angle scattering tensor tomography has enabled the study of anisotropic nanostructures in a volume-resolved manner. It is of great value to have reconstruction methods that can handle many different nanostructural symmetries. For such a method to be employed by researchers from a wide range of backgrounds, it is crucial that its reliance on prior knowledge about the system is minimized, and that it is robust under various conditions. Here, a method is presented that employs band-limited spherical functions to enable the reconstruction of reciprocal-space maps of a wide variety of nanostructures. This method has been thoroughly tested and compared with existing methods in its ability to retrieve known reciprocal-space maps, as well as its robustness to changes in initial conditions, using both simulations and experimental data. It has also been evaluated for its computational performance. The anchoring of this method in a framework of integral geometry and linear algebra highlights its possibilities and limitations.
AI-enabled human capital management (HCM) software adoption using full consistency method (FUCOM): evidence from banking industry
Authors: Yadav Rama Shankar , Kaya Sema Kayapinar , Pant Abhay , Tiwari Anurag
Published: October 2023

Purpose

Artificial intelligence (AI)-based human capital management (HCM) software solutions represent a potentially effective way to leverage and streamline a bank’s human resources. However, despite the attractiveness of AI-based HCM solutions to improve banks’ effectiveness, to the best of the authors’ knowledge, there are no current studies that identify critical success factors (CSFs) for adopting AI-based HCM in the banking sector. This study aims to fill this gap by investigating CSFs for adopting AI-based HCM software solutions in the banking sector.

Design/methodology/approach

Full consistency method methodology and technology–organization–environment, economic and human framework are used for categorizing and ranking CSFs.

Findings

The study identifies the technological and environmental dimensions as the most and least important dimensions for AI-based HCM adoption in banks. Among specific CSFs, compatible technology facilities, sufficient privacy and security and relative advantages of technology over competing technologies were identified as the most important. Implementation of AI-based HCM solutions requires significant outlays of resources, both human and financial, for banks.

Originality/value

The study provides bank administrators a set of objective parameters and criterion to evaluate the feasibility of adopting a particular AI-based HCM solution in banks.
Information governance orientation, supply chain strategy type and performance outcomes
Authors: In Joonhwan , Bradley Randy , Bichescu Bogdan C. , Han Sumin
Published: October 2023

Purpose

This study aims to examine the performance implications of an information governance (IG) framework for managing, controlling access to and securing information, focusing on (1) the performance benefits of an organization's IG orientation and (2) how the configuration of IG orientation and supply chain (SC) strategy type relate to performance outcomes.

Design/methodology/approach

This study leverages multiple secondary sources for US hospitals, serving as the context for the study. It also employs cluster analysis to develop an SC strategy taxonomy, namely sophisticated and delivery-focused SC strategies. The proposed research model is tested using a robust regression to mitigate the influence of outliers and produce more accurate estimates.

Findings

IG orientation is positively associated with financial performance and patient experience, and IG-oriented hospitals with a sophisticated SC strategy realize more financial benefits and achieve better patient care experiences compared to other configurations. Regardless of SC strategy type, IG-oriented hospitals offer better care experiences than non-IG-oriented hospitals.

Practical implications

This paper offers empirical evidence that a hospital's IG orientation and SC strategy jointly affect financial outcomes and patient experience. For hospitals, an organization-wide framework for governing information streamlines both intra- and inter-organizational information flows and improves care delivery throughout a patient's care experience.

Originality/value

This is one of a few studies that empirically examine the performance implications of governance of information in the domain of supply chain management (SCM). This study also develops an SC strategy taxonomy for the healthcare context and offers a springboard for research in service SC strategy.
Green servant leadership and green voice behavior in Qatari higher education: does climate for green initiative matter?
Authors: Aboramadan Mohammed , Barbar Julia , Alhabil Wasim , Alhalbusi Hussam
Published: October 2023

Purpose

Building on the theories of social learning and social information processing, this paper aims to examine the effect of green servant leadership (GSL) on green voice behavior among staff working in Qatari higher education. In this relationship, the climate for green initiative (CFGI) was used to act as a mediating mechanism.

Design/methodology/approach

Data in this study were collected from 275 staff working in Qatari higher education. Structural equation modeling was used to analyze the data.

Findings

The results suggest that GSL positively influences green voice behavior, whereas CFGI mediated this link.

Practical implications

The results can be beneficial to higher education pertaining to the importance of GSL in generating positive green behaviors such as green voice behavior. Furthermore, the results highlight the significant role CFGI plays in motivating such behaviors.

Originality/value

To the best of the authors’ knowledge, this is the first study that examines the link between GSL and green voice behavior in the higher education context. Furthermore, research on CFGI has received limited attention so far.
Taoism and current global crises: insights into ethics and governance
Authors: Reinert Kenneth
Published: October 2023

Purpose

The aim of the study is to assess the extent to which Taoist philosophy offers thematic and ethical insights relevant to current global crises, including climate change, food insecurity, renewed conflict and increased authoritarianism.

Design/methodology/approach

A critical review of specific verses from the Tao Te Ching and research sources relevant to them is carried out.

Findings

Taoist philosophy, of ancient origins, is surprisingly relevant to modern crises. While not offering definitive answers, it does provide thematic and ethical insights for reorienting governance in more productive ways.

Originality/value

While there is a large literature on Taoist philosophy itself, there is a paucity of research articles on the modern relevance of Taoist philosophy to pressing current issues. The article brings together and assesses these sources, considering relevant research.
An efficient thermal model for high-speed angular contact ball bearings based on oil-air two-phase flow and gray-box model
Authors: Zheng De-Xing , Zheng Dateng
Published: October 2023

Purpose

For a lightweight and accurate description of bearing temperature, this paper aims to present an efficient semi-empirical model with oil–air two-phase flow and gray-box model.

Design/methodology/approach

First, the role of lubricant/coolant in bearing temperature was discussed separately, and the gray-box models on the heat convection inside a bearing cavity were also created. Next, the bearing node setting scheme was optimized. Consequently, a novel semi-empirical two-phase flow thermal grid for high-speed angular contact ball bearings was planned. With this model, the thermal network for the selected motored spindle was built, and the numerical solutions for bearing temperature rise were obtained and contrasted with the experimental values for validation. The polynomial interpolation on test data, meanwhile, was also performed to help us observe the temperature change trend. Finally, the simulations based on the current models of bearings were implemented, whose corresponding results were also compared with our research work.

Findings

The validation result indicates that the thermal prediction is more accurate and efficient when the developed semi-empirical oil–air two-phase flow model is employed to assess the thermal change of bearings. Clearly, we provide a more proper model for the thermal assessment of bearing and even spindle heating.

Originality/value

To the best of the authors’ knowledge, this paper introduced the oil–air separation and gray-box model for the first time to describe the heat exchange inside bearing cavities and accordingly presents an efficient semi-empirical oil–air two-phase flow model to evaluate the bearing temperature variation by using thermal network method.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-06-2023-0180/
From vision to reality: how school leaders nurture deeper learning
Authors: Richardson Jayson W. , Bathon Justin , McLeod Scott
Published: October 2023

Purpose

This article details findings on how leaders of deeper learning schools establish, maintain, and propel unique teaching and learning environments. In this case study, the authors present findings from data collected through interviews with 30 leaders of self-proclaimed deeper learning initiatives and site visits to those elementary and secondary schools.

Design/methodology/approach

Using a case study approach, the authors collected data from interviews and observations of 30 school leaders.

Findings

The study's findings indicate how leaders of schools that engage in deeper learning tend to adhere to three core practices. First, the leaders of deeper learning schools in this study intently listened to the community to ascertain needs and desires; this drove the vision. Second, leaders of deeper learning schools created learning spaces that empowered students and gave them voice, agency, and choice. Third, leaders of deeper learning schools sought to humanize the schooling experience.

Practical implications

This study provides actionable examples of what leaders currently do to engage kids and teachers in deeper learning. These leaders offer insights into specific actions and practices that they espoused to make the schooling experience markedly different.

Originality/value

Previous studies focused on the deeper learning of schools and students. This is one of the first studies to focus on the inteplay between deeper learning and school leaders.