bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and systems characterization of phosphorylation on metabolic enzymes identifies sex-specific metabolic reprogramming in obesity
Authors: Tamir Tigist Y , Chaudhary Shreya , Li Annie X , Trojan Sonia E , Flower Cameron T , Vo Paula , Cui Yufei , Davis Jeffrey C , Mukkamala Rachit S , Venditti Francesca N , Hillis Alissandra L , Toker Alex , Vander Heiden Matthew G , Spinelli Jessica B , Kennedy Norman J , Davis Roger J , White Forest M
Published: August 2024

Coordination of adaptive metabolism through cellular signaling networks and metabolic response is essential for balanced flow of energy and homeostasis. Post-translational modifications such as phosphorylation offer a rapid, efficient, and dynamic mechanism to regulate metabolic networks. Although numerous phosphorylation sites have been identified on metabolic enzymes, much remains unknown about their contribution to enzyme function and systemic metabolism. In this study, we stratify phosphorylation sites on metabolic enzymes based on their location with respect to functional and dimerization domains. Our analysis reveals that the majority of published phosphosites are on oxidoreductases, with particular enrichment of phosphotyrosine (pY) sites in proximity to binding domains for substrates, cofactors, active sites, or dimer interfaces. We identify phosphosites altered in obesity using a high fat diet (HFD) induced obesity model coupled to multiomics, and interrogate the functional impact of pY on hepatic metabolism. HFD induced dysregulation of redox homeostasis and reductive metabolism at the phosphoproteome and metabolome level in a sex-specific manner, which was reversed by supplementing with the antioxidant butylated hydroxyanisole (BHA). Partial least squares regression (PLSR) analysis identified pY sites that predict HFD or BHA induced changes of redox metabolites. We characterize predictive pY sites on glutathione S-transferase pi 1 (GSTP1), isocitrate dehydrogenase 1 (IDH1), and uridine monophosphate synthase (UMPS) using CRISPRi-rescue and stable isotope tracing. Our analysis revealed that sites on GSTP1 and UMPS inhibit enzyme activity while the pY site on IDH1 induces activity to promote reductive carboxylation. Overall, our approach provides insight into the convergence points where cellular signaling fine-tunes metabolism.

Summary Statement

By employing a multi-disciplinary approach we stratify structural features of phosphorylation sites on metabolic enzymes, map the systems level changes induced by obesity, identify key pathways with sex specific phosphoproteomic responses, and validate the functional role of phosphorylation sites for select enzymes.
Extinction burst could be explained by curiosity-driven reinforcement learning
Authors: Yamada Kota , Matsui Hiroshi , Toda Koji
Published: August 2024

Curiosity encourages agents to explore their environment, leading to learning opportunities. Although psychology and neurobiology have tackled how external rewards control behavior, how intrinsic factors control behavior remains unclear. An extinction burst is a behavioral phenomenon in which a sudden increase in the frequency of a behavior immediately follows the omission of a reward. Although the extinction burst is textbook knowledge in psychology, there is little empirical evidence of it in experimental situations. In this study, we show that the extinction burst can be explained by curiosity by combining computational modeling of behavior and empirical demonstrations in mice. First, we built a reinforcement learning model incorporating curiosity, defined as expected reward prediction errors, and the model additively controlled the agent’s behavior to the primary reward. Simulations revealed that the curiosity-driven reinforcement learning model produced an extinction burst and burst intensity depended on the reward probability. Second, we established a behavioral procedure that captured extinction bursts in an experimental setup using mice. We conducted an operant conditioning task with head-fixed mice, in which the reward followed after pressing a lever at a given probability. After the training sessions, we occasionally withheld the reward delivery when the mice performed the task. We found that phasic bursts of responses occurred immediately after reward omission when responses were rewarded with a high probability, suggesting that the magnitude of reward prediction errors controlled the burst. These results provide theoretical and experimental evidence that intrinsic factors control behavior in adapting to an ever-changing environment.

Significance statement

In theories of learning and behavior, primary rewards such as food, water, and sex occupy a dominant position as factors controlling behavior. However, primary rewards are scarce. Experimental investigations in psychology, neuroscience, ethology, and economics have revealed that novelty, uncertainty, and unpredictability drive behavior. How these intrinsic factors affect behavior is essential for a comprehensive understanding of the principles of learning and behavior. This study provides theoretical and experimental evidence that operant responses in mice are directly controlled by external rewards and intrinsic factors such as curiosity. Our study provides a robust example of curiosity-driven behavior and paves the way for understanding the mechanism of curiosity.
Dissociation of putative open loop circuit from ventral putamen to motor cortical areas in humans I: high-resolution connectomics
Authors: Rizor Elizabeth , Dundon Neil M. , Wang Jingyi , Stasiak Joanne , Li Taylor , Bostan Andreea C. , Lapate Regina C. , Grafton Scott T.
Published: August 2024

Human movement is partly organized and executed by cortico-basal ganglia-thalamic closed-loop circuits (CLCs), wherein motor cortical areas both send inputs to and receive feedback from the basal ganglia, particularly the dorsal putamen (PUTd). These networks are compromised in Parkinson’s disease (PD) due to neurodegeneration of dopaminergic inputs primarily to PUTd. Yet, fluid movement in PD can sporadically occur, especially when induced by emotionally arousing events. Rabies virus tracing in non-human primates has identified a potential alternative motor pathway, wherein the ventral putamen (PUTv) receives inputs from subcortical limbic areas (such as amygdala nuclei) and sends outputs to motor cortical areas putatively via the nucleus basalis of Meynert (NBM). We hypothesize that this separable open loop circuit (OLC) may exist in humans and explain the preservation of movement after CLC degradation. Here, we provide evidence for the normal human OLC with ultra-high field (7T), multi-echo functional magnetic resonance imaging. We acquired resting-state functional connectivity (FC) scans from 21 healthy adults (avg. age = 29, 12M/9F, all right-handed) and mapped left-hemisphere seed-to-voxel connectivity to assess PUTv FC with putative subcortical nodes and motor cortical areas. We found that putative OLC node (basolateral amygdala, NBM) FC was greater with PUTv (p < 0.05), while CLC subcortical seed (ventrolateral nucleus of thalamus) FC was greater with PUTd (p<0.01). Striatal FC patterns varied across cortical motor areas, with cingulate (p < 0.0001) and supplementary (p < 0.0001) motor areas showing greater FC with PUTv vs. nucleus accumbens. SMA had greater FC with PUTd vs. PUTv (p < 0.0001), while cingulate and primary motor areas showed no significant differences in FC between PUTd and PUTv (p > 0.1). Collectively, these results suggest that PUTv is functionally connected to motor cortical areas and may be integrated into a separable motor OLC with subcortical limbic inputs.
DAMP-inducing Peptide Nanofibers and PAMP Combination Adjuvants Boost Functional Lung Tissue-resident Memory CD4+T Cell Responses
Authors: Files Megan A. , Das Anirban , Kim Darren , Buck Jeremy , Endsley Janice J. , Rudra Jai S.
Published: August 2024

Vaccine adjuvants are typically composed of pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) that activate innate immune cells. Advances in basic immunology have demonstrated the need for various ‘types’ of protective immunity, which are difficult to achieve with a single adjuvant. The FDA approval of multiple PAMP-DAMP combinations for clinical use has led to an increased momentum in the area in recent years. Here we report the use of DAMP-inducing peptide nanofibers (PNFs) and CL429 (PAMP) combinations as subunit boosters for Bacille Calmette-Guérin (BCG). We demonstrate that pulmonary boosting with PNFs and CL429 enhances the lung-resident memory phenotype, effector cytokine profiles, and transcription factor bias of antigen-specific CD4+T cell populations compared to PNFs alone. Importantly, the combination significantly improved the frequency of tissue-resident memory T (TRM) cells which, have been shown to provide superior protection compared to circulating memory T cells. Interestingly, the T helper (Th) subset profile was driven in part driven by the route of vaccination resulting in a Th17 bias via a mucosal route or a Th1 bias when delivered intravenously. We show that following pulmonary administration, lung-resident antigen presenting cells (APCs) efficiently internalize PNFs and upregulate important co-stimulatory markers that drive T cell priming and activation. Our findings suggest that heterologous booster vaccines composed of DAMP-inducing PNFs and PAMP combinations can engage innate and adaptive immunity for generating TRMcells that protect against TB and potentially other respiratory diseases.
Benchmarking residue-resolution protein coarse-grained models for simulations of biomolecular condensates
Authors: Feito Alejandro , Sanchez-Burgos Ignacio , Tejero Ignacio , Sanz Eduardo , Rey Antonio , Collepardo-Guevara Rosana , Tejedor Andres R. , Espinosa Jorge R.
Published: August 2024

Intracellular liquid–liquid phase separation (LLPS) of proteins and nucleic acids is a fundamental mechanism by which cells compartmentalize their components and perform essential biological functions. Molecular simulations play a crucial role in providing microscopic insights into the physicochemical processes driving this phenomenon. In this study, we systematically compare six state-of-the-art sequence-dependent, residue-resolution models to evaluate their performance in reproducing the phase behaviour and material properties of condensates formed by seven variants of the low-complexity domain (LCD) of the hnRNPA1 protein (A1-LCD)—a protein implicated in the pathological liquid-to-solid transition of stress granules. Specifically, we assess the HPS, HPS-cation–π, HPS-Urry, CALVADOS2, Mpipi, and Mpipi-Recharged models in their predictions of the condensate saturation concentration, critical solution temperature, and condensate viscosity for the A1-LCD variants. Our analyses demonstrate that, among the tested models, Mpipi, Mpipi-Recharged, and CALVADOS2 provide accurate descriptions of the critical solution temperatures and saturation concentrations for the various A1-LCD variants tested. Regarding the prediction of material properties for condensates of A1-LCD and its variants, Mpipi-Recharged stands out as the most reliable model. Overall, this study benchmarks a range of residue-resolution coarse-grained models for the study of the thermodynamic stability and material properties of condensates and establishes a direct link between their performance and the ranking of intermolecular interactions these models consider.
Region-specific Nucleus Accumbens Dopamine Signals Encode Distinct Aspects of Avoidance Learning
Authors: Lopez Gabriela C. , Van Camp Louis D. , Kovaleski Ryan F. , Schaid Michael D. , Andrés Moreno-Ramos Oscar , Awatramani Rajeshwar , Cox Julia M. , Lerner Talia N.
Published: August 2024

Avoidance learning – learning to avoid bad outcomes – is an essential survival behavior. Dopamine signals are widely observed in response to aversive stimuli, indicating they could play a role in learning about how to avoid these stimuli. However, it is unclear what computations dopamine signals perform to support avoidance learning. Furthermore, substantial heterogeneity in dopamine responses to aversive stimuli has been observed across nucleus accumbens (NAc) subregions. To understand how heterogeneous dopamine responses to aversive stimuli contribute to avoidance learning, we recorded NAc core (Core) and NAc ventromedial shell (vmShell) dopamine during a task in which mice could avoid a footshock punishment by moving to the opposite side of a 2-chamber apparatus during a five-second warning cue. We found that NAc Core and vmShell dopamine signals responded oppositely during shocks and warning cues. Both signals evolved substantially – but differently – with learning. NAc vmShell dopamine responses to cues and shocks were present during early learning but not sustained during expert performance. NAc Core dopamine responses strengthen with learning and are especially evident during expert performance. Our data support a model in which NAc vmShell dopamine guides initial cue-shock associations by signaling salience, while NAc Core dopamine encodes prediction errors that guide the consolidation of avoidance learning.
Integrative Analysis of Gene Expression, Protein Abundance, and Metabolomic Profiling Elucidates Complex Relationships in Chronic Hyperglycemia-Induced Changes in Human Aortic Smooth Muscle Cells
Authors: Bohara Smriti , Bagheri Atefeh , Ertugral Elif G. , Radzikh Igor , Sandlers Yana , Jiang Peng , Kothapalli Chandrasekhar R.
Published: August 2024

Type 2 diabetes mellitus (T2DM) is a major public health concern with significant cardiovascular complications (CVD). Despite extensive epidemiological data, the molecular mechanisms relating hyperglycemia to CVD remain incompletely understood. We here investigated the impact of chronic hyperglycemia on human aortic smooth muscle cells (HASMCs) cultured under varying glucose conditionsin vitro, mimicking normal (5 mmol/L), pre-diabetic (10 mmol/L), and diabetic (20 mmol/L) conditions, respectively. Patient-derived T2DM-SMCs served as disease phenotype controls. Results showed significant increases in cellular proliferation, area, perimeter, and F-actin expression with increasing glucose concentration (p< 0.01), albeit not exceeding the levels in T2DM cells. Atomic force microscopy analysis revealed significant decreases in Young’s moduli, membrane tether forces, membrane tension, and surface adhesion in SMCs at higher glucose levels (p< 0.001), with T2DM-SMCs being the lowest among all the cases (p< 0.001). T2DM-SMCs exhibited elevated levels of pro-inflammatory markers such as IL-6, IL-8, and MCP-1 compared to glucose-treated SMCs (p< 0.01). Conversely, growth factors such as FGF-2 and TGF-β were higher in SMCs exposed to 10 mmol/L glucose but lower in T2DM-SMCs (p< 0.01). Pathway enrichment analysis showed significant increases in the expression of inflammatory cytokine-associated pathways, especially involving IL-10, IL-4 and IL-13 signaling in genes that are up-regulated by elevated glucose levels. Differentially regulated gene (DGE) analysis showed that compared to normal glucose receiving SMCs, 513 genes were upregulated and 590 genes were downregulated in T2DM-SMCs; fewer genes were differentially expressed in SMCs receiving higher glucose levels. Finally, the altered levels in genes involved in ECM organization, elastic fiber synthesis and formation, laminin interactions, and ECM proteoglycans were identified, which highlight the role of hyperglycemia in vascular remodeling and CVD progression. Our results collectively suggest that chronic hyperglycemia in vascular SMCs leads to morphological, biomechanical, and functional alterations, potentially contributing to the pathogenesis of T2DM-associated CVD. The observed differences in gene expression patterns betweenin vitrohyperglycemic models and patient-derived T2DM-SMCs highlight the complexity of T2DM pathophysiology and underline the need for further studies.
FREQ-NESS Reveals the Dynamic Reconfiguration of Frequency-Resolved Brain Networks During Auditory Stimulation
Authors: Rosso M. , Fernández-Rubio G. , Keller P. , Brattico E. , Vuust P. , Kringelbach M. L. , Bonetti L.
Published: August 2024

The brain is a dynamic system whose network organization is often studied by focusing on specific frequency bands or anatomical regions, leading to fragmented insights, or by employing complex and elaborate methods that hinder straightforward interpretations. To address this issue, a new analytical pipeline namedFREQuency-resolved Network Estimation via Source Separation(FREQ-NESS) is introduced. This is designed to estimate the activation and spatial configuration of simultaneous brain networks across frequencies by analyzing the frequency-resolved multivariate covariance between whole-brain voxel time series. FREQ-NESS is applied to source-reconstructed magnetoencephalography (MEG) data during resting state and isochronous auditory stimulation. Results reveal simultaneous, frequency-specific brain networks during resting state, such as the default mode, alpha-band, and motor-beta networks. During auditory stimulation, FREQ-NESS detects: (1) emergence of networks attuned to the stimulation frequency, (2) spatial reorganization of existing networks, such as alpha-band networks shifting from occipital to sensorimotor areas, (3) stability of networks unaffected by auditory stimuli. Furthermore, auditory stimulation significantly enhances cross-frequency coupling, with the phase of attuned auditory networks modulating the gamma band amplitude of medial temporal lobe networks. In conclusion, FREQ-NESS effectively maps the brain’s spatiotemporal dynamics, providing a comprehensive view of brain function by revealing simultaneous, frequency-resolved networks and their interaction.
Transformations in prefrontal ensemble activity underlying rapid threat avoidance learning
Authors: Gabriel Christopher J. , Gupta Tanya , Sanchez-Fuentes Asai , Zeidler Zachary , Wilke Scott A. , DeNardo Laura A.
Published: August 2024

The capacity to learn cues that predict aversive outcomes, and understand how to avoid those outcomes, is critical for adaptive behavior. Naturalistic avoidance often means accessing a safe location, but whether a location is safe depends on the nature of the impending threat. These relationships must be rapidly learned if animals are to survive. The prelimbic subregion (PL) of the medial prefrontal cortex (mPFC) integrates learned associations to influence these threat avoidance strategies. Prior work has focused on the role of PL activity in avoidance behaviors that are fully established, leaving the prefrontal mechanisms that drive rapid avoidance learning poorly understood. To determine when and how these learning-related changes emerge, we recorded PL neural activity using miniscope calcium imaging as mice rapidly learned to avoid a threatening cue by accessing a safe location. Over the course of learning, we observed enhanced modulation of PL activity representing intersections of a threatening cue with safe or risky locations and movements between them. We observed rapid changes in PL population dynamics that preceded changes observable in the encoding of individual neurons. Successful avoidance could be predicted from cue-related population dynamics during early learning. Population dynamics during specific epochs of the conditioned tone period correlated with the modeled learning rates of individual animals. In contrast, changes in single-neuron encoding occurred later, once an avoidance strategy had stabilized. Together, our findings reveal the sequence of PL changes that characterize rapid threat avoidance learning.
Label-free acoustic and optical microscopy of live tumor spheroids in hydrogel for high-throughput 3D In-vitro drug screening
Authors: Ghosh Biswajoy , Agarwal Komal , Habib Anowarul , Agarwal Krishna , Melandsø Frank
Published: August 2024

3D cell cultures, including spheroids, have become essential tools in cancer research and drug discovery due to their ability to more accurately mimic in-vivo tissue environments compared to traditional 2D cultures. However, imaging these thick, complex structures remains a challenge, as conventional optical microscopy techniques are limited by shallow depth penetration. This study explores the complementary use of gradient light interference microscopy (GLIM) and scanning acoustic microscopy (SAM) for label-free imaging of 3D spheroid clusters embedded in hydrogels. GLIM offers high-resolution optical imaging but struggles with depth in dense samples, while SAM provides greater depth penetration and a larger field of view, albeit with lower resolution. By correlating SAM and GLIM imaging, this study demonstrates how the two techniques can be synergistically used to enhance the visualization of spheroids, capturing both large-scale structural features and fine cellular details. The benefits make such a platform suitable for screening high-number multi-well plates and evaluating necrotic and angiogenic features from the core of the thick sample. Such platforms have the potential of combining acoustic and optical imaging modalities for high-throughput screening and physical characterization in 3D cell culture research, advancing our understanding of drug efficacy in complex biological systems.
The SP140-RESIST pathway regulates interferon mRNA stability and antiviral immunity
Authors: Witt Kristen C. , Dziulko Adam , An Joohyun , Pekovic Filip , Cheng Arthur Xiuyuan , Liu Grace Y. , Lee Ophelia Vosshall , Turner David J. , Lari Azra , Gaidt Moritz M. , Chavez Roberto , Fattinger Stefan A. , Abraham Preethy , Dhaliwal Harmandeep , Lee Angus Y. , Kotov Dmitri I. , Coscoy Laurent , Glaunsinger Britt A. , Valkov Eugene , Chuong Edward B. , Vance Russell E.
Published: August 2024

Type I interferons (IFN-Is) are essential for antiviral immunity but must be tightly regulated1–3. The conserved transcriptional repressor SP140 inhibits interferon beta (Ifnb1) expression via an unknown mechanism4,5. Here we report that SP140 does not directly repressIfnb1transcription. Instead, SP140 negatively regulatesIfnb1mRNA stability by directly repressing the expression of a previously uncharacterized regulator we call RESIST (REgulated Stimulator of Interferon via Stabilization of Transcript, previously annotated as Annexin-2 Receptor). RESIST promotesIfnb1mRNA stability by counteractingIfnb1mRNA destabilization mediated by the Tristetraprolin (TTP) family of RNA-binding proteins and the CCR4-NOT deadenylase complex. SP140 localizes within nuclear bodies, punctate structures that play important roles in silencing DNA virus gene expression in the nucleus4. Consistent with this observation, we found that SP140 inhibits replication of the gammaherpesvirus MHV68. The antiviral activity of SP140 was independent of its ability to regulateIfnb1. Our results establish dual antiviral and interferon regulatory functions for SP140. We propose that SP140 and RESIST participate in antiviral effector-triggered immunity6,7.
Design of diverse, functional mitochondrial targeting sequences across eukaryotic organisms using variational autoencoder
Authors: Boob Aashutosh Girish , Tan Shih-I , Zaidi Airah , Singh Nilmani , Xue Xueyi , Zhou Shuaizhen , Martin Teresa A. , Chen Li-Qing , Zhao Huimin
Published: August 2024

Mitochondria play a key role in energy production and cellular metabolism, making them a promising target for metabolic engineering and disease treatment. However, despite the known influence of passenger proteins on localization efficiency, only a few protein-localization tags have been characterized for mitochondrial targeting. To address this limitation, we exploited Variational Autoencoder (VAE), an unsupervised deep learning framework, to design novel mitochondrial targeting sequences (MTSs).In silicoanalysis revealed that a high fraction of generated peptides are functional and possess features important for mitochondrial targeting. Additionally, we devised a sampling scheme to indirectly address biases arising from the differences in mitochondrial protein import machinery and characterized artificial MTSs in four eukaryotic organisms. These sequences displayed significant diversity, sharing less than 60% sequence identity with MTSs in the UniProt database. Moreover, we trained a separate VAE and employed latent space interpolation to design dual targeting sequences capable of targeting both mitochondria and chloroplasts, shedding light on their evolutionary origins. As a proof-of-concept, we demonstrate the application of these artificial MTSs in increasing titers of 3-hydroxypropionic acid through pathway compartmentalization and improving 5-aminolevulinate synthase delivery by 1.62-fold and 4.76-fold, respectively. Overall, our work not only demonstrates the potential of generative artificial intelligence in designing novel, functional mitochondrial targeting sequences but also highlights their utility in engineering mitochondria for both fundamental research and practical applications in biology.
Multi-scale reactor designs extend the physical limits of CO2fixation
Authors: Akbari Amir , Palsson Bernhard O.
Published: August 2024

CO2valorization is a promising strategy for climate adaptation and transitioning towards a circular carbon economy. Here, we present a multi-scale, integrated systems approach for designing biomanufacturing systems that can utilize CO2as a feedstock, focusing on the Wood–Ljungdahl and reductive glycine pathways. This approach relies on first principles, coupling the optimization of pathway and process variables. We examine the CO2-fixation capacity of both pathways in single- and multi-compartment reactor systems, demonstrating that the reductive glycine pathway has the potential to fix CO2at significantly higher rates than photosynthetic organisms. We show that small differences in the energy-dissipative and stoichiometric structures of carbon-fixation pathways could significantly impact optimal designs and feasible design spaces. Our first-principle, systems-level approach quantifies these differences and uncovers strategies to expand the design space and extend the physical limits of carbon fixation, offering insights into pathway selection and process configurations for efficient biomanufacturing.
Inflammatory reprogramming of the tumor microenvironment by infiltrating clonal hematopoiesis is associated with adverse outcomes in solid cancer
Authors: Buttigieg Marco M. , Vlasschaert Caitlyn , Bick Alexander G. , Vanner Robert J. , Rauh Michael J.
Published: August 2024

Clonal hematopoiesis (CH) – the expansion of somatically-mutated hematopoietic cells in blood – is common in solid cancers. CH is associated with systemic inflammation that may lead to cancer, but its impact on tumor biology is underexplored. Here, we report the effects of CH on the tumor microenvironment (TME) using 1,550 treatment-naïve patient samples from the CPTAC cohort. CH was present in 18.3% of patients, with one-third of CH mutations also detectable in tumor-derived DNA from the same individual (CH-Tum), reflecting CH-mutant leukocyte infiltration. The presence of CH-Tum was associated with worse survival across cancers, particularly for glioblastoma.

Transcriptomics and proteomics revealed that CH drives inflammation in the TME in a cancer- and CH driver-specific manner, and may improve immunotherapy responses. In glioblastoma, CH associated with pronounced macrophage infiltration, inflammation, and an aggressive, mesenchymal phenotype. Our findings demonstrate that CH shapes the TME, with potential applications as a biomarker in precision oncology.
A-Islands: A plant dataset for biodiversity research and species monitoring on Australian islands
Authors: Schrader Julian , Coleman David , Abbott Ian , Bryant Sally , Buckley Ralf , Crayn Darren , Gallagher Rachael V. , Harris Stephen , Heatwole Harold , Jackes Betsy , Kreft Holger , Mills Kevin , Kirkpatrick Jamie , Latz Peter K. , Neldner John , Sattler Cornelia , Visoiu Micah , Wenk Elizabeth H. , Woinarski John C. Z. , Worboys Stuart , Wright Ian J. , Zorn Isabel , Westoby Mark
Published: August 2024

Australia’s coastline is fringed by more than 8,000 continental islands. These islands feature a diverse array of landforms, rock and soil types and geological origins. Some of these islands are among the least invaded, most pristine habitats in Australia and support high plant diversity. Here, we present a new Australia-wide curated dataset for plant species occurrences on islands. Combining information from 1,349 species lists and floras, A-Islands includes data on >6,500 plant species from 844 islands ranging in size from 18 m2to 4,400 km2, exhibiting different degrees of isolation from the mainland, and spanning all major Australian climate zones. Of these, 251 islands have been repeatedly sampled up to 11 times making it possible to investigate temporal compositional change. A-Islands is open access and will be continuously updated. Its simple data structure consisting of three comma separated files allows easy integration with other Australian and global plant-occurrence databases and can serve as a repository for island research in Australia. Knowing which species occur on Australia′s islands will provide opportunities for future research, including studying changes in biodiversity and species-turnover within and among archipelagos, tests of classical island biogeography theory and as a baseline for ecological monitoring and conservation.
A dual ribosomal system in the zebrafish soma and germline
Authors: Shah Arish N , Leesch Friederike , Lorenzo-Orts Laura , Grundmann Lorenz , Novatchkova Maria , Haselbach David , Calo Eliezer , Pauli Andrea
Published: August 2024

Protein synthesis during vertebrate embryogenesis is driven by ribosomes of two distinct origins: maternal ribosomes synthesized during oogenesis and stored in the egg, and somatic ribosomes, produced by the developing embryo after zygotic genome activation (ZGA). In zebrafish, these two ribosome types are expressed from different genomic loci and also differ in their ribosomal RNA (rRNA) sequence. To characterize this dual ribosome system further, we examined the expression patterns of maternal and somatic rRNAs during embryogenesis and in adult tissues. We found that maternal rRNAs are not only expressed during oogenesis but are continuously produced in the zebrafish germline. Proteomic analyses of maternal and somatic ribosomes unveiled differences in core ribosomal protein composition. Most nucleotide differences between maternal and somatic rRNAs are located in the flexible, structurally not resolved expansion segments. Our in vivo data demonstrated that both maternal and somatic ribosomes can be translationally active in the embryo. Using transgenically tagged maternal or somatic ribosome subunits, we experimentally confirm the presence of hybrid 80S ribosomes composed of 40S and 60S subunits from both origins and demonstrate the preferential in vivo association of maternal ribosomes with germline-specific transcripts. Our study identifies a distinct type of ribosomes in the zebrafish germline and thus presents a foundation for future explorations into possible regulatory mechanisms and functional roles of heterogeneous ribosomes.
The pro-apoptotic effect of chronic contractile activity-induced extracellular vesicles on Lewis Lung Carcinoma cells
Authors: Obi Patience O. , Souza Tamiris F.G. , McManus Kirk J. , West Adrian R. , Gordon Joseph W. , Saleem Ayesha
Published: August 2024

Regular exercise reduces tumor growthin vivoandin vitro, but the exact mechanisms have yet to be fully elucidated. We have previously shown that chronic contractile activity (CCA) increases the concentration of skeletal muscle-derived EVs, and these in turn increased mitochondrial biogenesis in myoblasts. Here, we hypothesized that skeletal muscle-EVs derived post-CCA will mediate the anti-tumorigenic effects associated with chronic exercise. C2C12 myoblasts were differentiated into myotubes, electrically paced, and EVs isolated from conditioned media from control and CCA myotubes using differential ultracentrifugation. Lewis lung carcinoma (LLC) cells were treated with the total number of control-EVs or CCA-EVs isolated after each day of contractile activity for 4 days. Permeabilized CCA-EVs with or without proteinase K before co-culture with LLC cells were used as controls. Effect of EV treatment on cell count, viability, apoptosis, senescence, migration, and mitochondrial content was measured. CCA-EV treatment reduced cell count by 18% and cell viability by 6%vs.control-EVs. CCA-EVs increased the incidence of apoptotic hallmarks: DNA fragmentation by 13%, Annexin V+/PI+ cells by 21%, and the expression of pro-apoptotic Bax (by 25%) and Bax/Bcl-2 ratio (by 60%)vs.control-EVs. CCA-EVs increased number of senescent cells by 29%, and senescence markers, HMGB1 (by 49%) and p16 (by 92%)vs.control-EVs. When CCA-EVs were pretreated with Triton X-100 with or without proteinase-K, the increase in apoptosis and senescence was abrogated, confirming the effect is due to intact EVs and likely through EV membrane-proteins. CCA-EVs did not have any effect on cell migration and mitochondrial contentvs.control-EVs. This study illustrates for the first time the potential of CCA-induced skeletal muscle-EVs in mediating anti-tumorigenic effects traditionally linked with chronic exercise.
Modulating Bacterial Nanocellulose Crystallinity through Post-Transcriptional Repression inKomagataeibacter xylinus
Authors: Mangayil Rahul , Sarlin Essi , Ellis Tom , Santala Ville
Published: August 2024

Bacterial nanocellulose (BC), a versatile and biodegradable polymer, has been extensively studied as an alternative biomaterial for various applications. For biomedical and packaging uses, where precise control over nanocellulose structure is essential, existing literature describes BC structural modification processes that involve additives or additional steps. With the aim to develop a programmable method to control the bulk microstructure, we developed sRNA-based post-transcriptional repression cassettes that allows precise regulation of the crystalline phase of BC. Before investigating the effects of post-transcriptional repression ofbcsD, bcsZ, andccpAgenes, known to influence BC crystallinity, we validated the specificity of the sRNA repression cassette by targeting a genome-integrated red fluorescent protein, mRFP1. The observed growth inhibition (>80%) caused by overexpressed Hfq RNA chaperone inKomagataeibacter xylinuswas alleviated (≤ 23%) by its removal, resulting in a 43% reduction in relative mRFP1 expression. By varying the design of the repression cassette and the inducer concentrations, we successfully modulated the repression of the target genes [with relative expression reductions of 6%-34% for bcsD, 8%-24% for bcsZ, and 2%-20% for ccpA, as confirmed by qRT-PCR]. These gene repression levels led to statistically significant changes in the amorphous content of the BC microstructure, as demonstrated by X-ray diffraction and wide-angle X-ray scattering analysis.
PKA prevents resection of DNA double strand breaks and favor non-homologous end-joining
Authors: Khater-Sellou Houaria , Magdalou Indiana , Ogryzko Vasily , Lopez Bernard S.
Published: August 2024

Genome rearrangement is a hallmark of cancer and ageing. DNA double-strand breaks (DSBs) are highly toxic lesions that can generate genome rearrangements. Several pathways compete for DSB repair, and selection of the appropriate repair process is decisive for genetic stability. DSB repair act according to two steps: 1-the choice between nonhomologous end-joining (NHEJ)versusresection of DNA ends, generating single-stranded DNA (ssDNA); 2-on ssDNA, homologous recombination (HR) and sub-processes. Here we show that 53BP1, which plays a prime role at the first step by protecting against resection and fostering NHEJ, physically interacts with the catalytic subunits of the cAMP dependant protein kinase A (PKAcs). PKA favors the recruitment of 53BP1 at DNA damages sites, and consistently, prevents resection, favoring NHEJ. Inhibition of PKA stimulated resection and coherently reduces NHEJ. Reversely, activation of PKA with 8-Bromo-cAMP stimulate NHEJ and reduces HR. These data open new avenues for potential anticancer strategies. More generally, they underline the high complexity of the regulation of DSB repair, identifying PKA as a novel actor of the DNA damage response, acting at the choice of the DSB repair process, which might be essential for genome integrity maintenance.
Muon
g−2
, long-range muon spin force, and neutrino oscillations
Authors: Fang Rundong , Guo Ji-Heng , Liu Jia , Wang Xiao-Ping
Published: August 2024

Recent studies have proposed using a geocentric muon spin force to account for the (g−2)μ anomaly, with the long-range force mediator being a light axionlike particle. The mediator exhibits a CP-violating scalar coupling to nucleons and a normal derivative coupling to muons. Due to the weak symmetry, this axion inevitably couples to neutrinos, providing potential impact on neutrino oscillations. By utilizing neutrino data from BOREXINO, IceCube DeepCore, Super-Kamiokande, and SNO, we have identified that both atmospheric and solar neutrino data can impose stringent constraints on the long-range muon spin force model and the (g−2)μ parameter space. With optimized data analysis techniques and the potential from future experiments, such as JUNO, Hyper-Kamiokande, SNO+, and IceCube PINGU, there exists a promising opportunity to achieve even greater sensitivities. Indeed, neutrino oscillations offer a robust and distinctive cross-check for the model, offering stringent constraints on the (g−2)μ parameter space.

Published by the American Physical Society
2024
Practical courses on advanced methods in macromolecular crystallization: 20 years of history and future perspectives
Authors: Havlickova Petra , Gavira Jose A. , Mesters Jeroen R. , Koutska Anna , Kascakova Barbora , Prudnikova Tatyana , Hilgenfeld Rolf , Garcia-Ruiz Juan Manuel , Rezacova Pavlina , Kuta Smatanova Ivana
Published: August 2024

The first Federation of European Biochemical Societies Advanced Course on macromolecular crystallization was launched in the Czech Republic in October 2004. Over the past two decades, the course has developed into a distinguished event, attracting students, early career postdoctoral researchers and lecturers. The course topics include protein purification, characterization and crystallization, covering the latest advances in the field of structural biology. The many hands-on practical exercises enable a close interaction between students and teachers and offer the opportunity for students to crystallize their own proteins. The course has a broad and lasting impact on the scientific community as participants return to their home laboratories and act as nuclei by communicating and implementing their newly acquired knowledge and skills.
Norfloxacinium nitrate
Authors: Rasulov Abdusamat , Torambetov Batirbay , Alimnazarov Bekmurod , Kadirova Shakhnoza , Suyunov Jabbor , Nazarov Yusufjon , Ashurov Jamshid
Published: August 2024

In the title salt [systematic name: 4-(3-carboxy-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinolin-7-yl)piperazin-1-ium nitrate], C16H19FN3O3
+·NO3
−, proton transfer from nitric acid to the N atom of the piperazine ring of norfloxacin has occurred to form a molecular salt. In the extended structure, N—H...O hydrogen bonds link alternating cations and anions into [100] chains, which are reinforced by aromatic π–π stacking interactions between the quinoline moieties of the norfloxacinium cations.
Sustainability in business education: a systematic review and future research agenda
Authors: Beamond Maria Teresa , Schmitz Marina , Cordova Miguel , Ilieva Maria Vasileva , Zhao Shasha , Panina Daria
Published: August 2024

Purpose

This paper aims to clarify how business education has and should incorporate more resources, policies and stakeholder engagement towards the incorporation of sustainability, by conducting a literature review on sustainability in business and international business education and proposing future opportunities for researchers and practitioners.

Design/methodology/approach

The authors take a systematic, qualitative analysis approach to evaluate multidisciplinary literatures on sustainability in business education. The authors identify 192 qualifying papers published in 68 journals between 2015 and 2023.

Findings

The authors propose five categories of education solutions. Four of them are integrated, in two macro–micro levels: university (stakeholders and shared-mindset change) and student (pedagogical methods and curriculum); and one at meso level: international business (holistic integration) serving to unify the university and student levels.

Research limitations/implications

The review highlights the value of applying a holistic approach and interdisciplinary pedagogical methods in future research on sustainability education in business school to effectively prepare future business leaders to contribute to a more sustainable future.

Practical implications

Insights from this review can usefully guide scholars and programme directors in their future research and administrative efforts towards business curriculum design, stakeholder management and policy-making.

Social implications

The findings highlight how by embracing holistic perspectives, proper policies and self-awareness, business education shapes the mindsets and skill sets of the next generation of socially conscious practitioners.

Originality/value

The review stands out as one of the few that offers a forward-looking trajectory for the adaptation of international business education in response to sustainability challenges, through a holistic perspective.
Harnessing generative AI for self-directed learning: Perspectives from top management
Authors: Jayasinghe Shan
Published: August 2024

Purpose

The purpose of this paper is to explore the potential of generative AI-driven self-directed learning from the perspective of top management in the Sri Lankan software industry. By applying open innovation theory, the study aims to understand how business leaders perceive the integration of generative AI tools in organizational learning processes. The insights gained are intended to inform and encourage top management to promote generative AI-driven self-directed learning within their organizations.

Design/methodology/approach

The research utilized a qualitative approach, conducting semi-structured interviews with eight senior managers from IT companies in Colombo, Sri Lanka. Data was synthesized and analyzed thematically to identify patterns and insights regarding generative AI-driven self-directed learning and its organizational impact.

Findings

The study reveals that top management in Sri Lanka's software industry perceives generative AI-driven self-directed learning positively. This perception is rooted in the alignment of such learning with open innovation principles, emphasizing knowledge sharing, collaboration and the integration of external expertise to drive innovation. Generative AI tools empower employees to access diverse knowledge sources, fostering continuous learning and adaptability. Leaders recognize these tools' potential to enhance organizational innovation ecosystems and competitive advantage. The findings suggest that active support from top management, customized training programs and a culture that embraces continuous learning and innovation are crucial for successful implementation.

Originality/value

This paper uniquely explores generative AI-driven self-directed learning through the lens of top management in Sri Lanka's software industry, integrating open innovation theory to highlight its potential in enhancing organizational knowledge, collaboration and competitive advantage.
User-centred collection metadata: from images as information to facilitating socio-affective connections
Authors: Kist Cassandra , Economou Maria
Published: August 2024

Purpose

As museums and other memory institutions continue to invest considerably in mass-digitising collections and participating in large search portals, it is essential to understand existing and potential users, their motivations and search needs to inform collections’ documentation. In this article, we discuss insights from a collaborative project with National Museums Scotland, set up to enhance the findability of collection images and inform documentation practices by understanding the collections users and their search terms.

Design/methodology/approach

The research involved interviews with National Museums Scotland staff, users and non-users of the Museums’ Search our Collections portal encompassing a concept mapping and card sort activity; online surveys and content analysis of user search queries.

Findings

The project revealed that participants are interested in searching the online collections by terms often not represented in collections metadata, including terms related to identity (their own but also others’) and social context (e.g. through seasonal and social events); emotional and sensory interests (e.g. visual characteristics) and narrative themes (e.g. on under-represented histories).

Originality/value

Based on the findings, we further theorise the semantic gap in online museum collection metadata. To bridge this gap and cater to how users search, we argue for a paradigm shift in documentation practices: suggesting practitioners should not only view collection images as information but also tap into their rich potential for enabling social and affective connections.
Introducing ESG controversies as the polluting factor of banks’ activity: a nonparametric efficiency approach
Authors: Dipierro Anna Rita , Toma Pierluigi , Frittelli Massimo
Published: August 2024

Purpose

Whether environmental, social and governance (ESG) factors are a curse or a blessing in the run for performance is still a burning issue. This is all the more true for banks, as their call for action in ESG dimensions clashes with evidence of scandals. As a more aligned to reality view, we propose to regard the mistreatment of ESG issues, both theoretically and empirically, as an undesirable output of banks' everyday activity. Empirically, we question whether 128 leading banks worldwide neglected the minimisation of ESG controversies (ESGC) in pursuing traditional productive efficiency, over the timespan 2011–2021.

Design/methodology/approach

To our end, we use oriented distance functions according to the nonparametric efficiency approach of data envelopment analysis (DEA). This framework accounts for undesirable outputs.

Findings

Being inefficient in the ESGC domain is not a necessary evil to achieve productive efficiency. Instead, incurring in higher ESGC negatively affects productive efficiency, by causing future decrease of reputation and performance.

Originality/value

We propose a new paradigm of banks’ activity and related efficiency evaluation. In so doing, we favour a real dimension of banks’ engagement in ESG concerns.