bluuebunny/crossref_metadata_2025 huggingface dataset:
Immersive Virtual Reality as a Tool to Reduce Anxiety and Distress in Patients With Breast Cancer During Radiotherapy
Authors: Aydin Aydanur , Uslu Gonca Hanedan , Gursoy Ayla
Published: November 2024

Background

Virtual reality (VR) can be an innovative method to reduce patients’ anxiety and support their psychological health.

Objective

To evaluate the anxiety and distress-reducing effects of using immersive VR (IVR) intervention in breast cancer patients undergoing radiotherapy (RT).

Methods

Sixty breast cancer patients undergoing RT were recruited for the quasi-experimental study. The participants were divided into the intervention group and the control group. Anxiety and distress, the primary outcome measures, were assessed before the first and after the last radiation session using reliable scales. Patients in the intervention group watched a tranquil forest view with birdsong and meditation music during each RT session using IVR goggles.

Results

Both group patients had similar levels of anxiety and distress before the start of RT. After the intervention, the anxiety and distress of the patients in the intervention group decreased significantly compared with the control group. In addition, treatment-related comfort was higher in the intervention group. Overall, the majority of patients in the intervention group expressed a high level of satisfaction with this IVR experience.

Conclusion

Patients who experienced an IVR intervention showed less anxiety and distress, greater comfort, and higher satisfaction. This innovative technique can be used as a practical solution to alleviate anxiety and distress in various healthcare settings.

Implications for Practice

Immersive VR can be used in treatment and care interventions that cause anxiety and distress in oncology patients.
Debunking revolutionary paradigm shifts: evidence of cumulative scientific progress across science
Authors: Krauss Alexander
Published: November 2024

How can scientific progress be conceived best? Does science mainly undergo revolutionary paradigm shifts? Or is the evolution of science mainly cumulative? Understanding whether science advances through cumulative evolution or through paradigm shifts can influence how we approach scientific research, education and policy. The most influential and cited account of science was put forth in Thomas Kuhn’s seminal book
The structure of scientific revolutions
. Kuhn argues that science does not advance cumulatively but goes through fundamental paradigm changes in the theories of a scientific field. There is no consensus yet on this core question of the nature and advancement of science that has since been debated across science. Examining over 750 major scientific discoveries (all Nobel Prize and major non-Nobel Prize discoveries), we systematically test this fundamental question about scientific progress here. We find that three key measures of scientific progress—major discoveries, methods and fields—each demonstrate that science evolves cumulatively. First, we show that no major
scientific methods or instruments
used across fields (such as statistical methods, X-ray methods or chromatography) have been completely abandoned, i.e. subject to paradigm shifts. Second, no major
scientific fields
(such as biomedicine, chemistry or computer science) have been completely abandoned. Rather, they have all continuously expanded over time, often over centuries, accumulating extensive bodies of knowledge. Third,
scientific discoveries
including theoretical discoveries are also predominately cumulative, with only 1% of over 750 major discoveries having been abandoned. The continuity of science is most compellingly evidenced by our methods and instruments, which enable the creation of discoveries and fields. We thus offer here a new perspective and answer to this classic question in science and the philosophy and history of science by utilizing methods from statistics and empirical sciences.
Coordination of flux-related leaf and root traits impacts forest community assembly
Authors: Ma Zeqing , Duan Mengcheng , Sack Lawren , Ma Chengen , Li Le , McCormack M. Luke , Lu Mingzhen , Guo Dali
Published: November 2024

Understanding the functions and coordination of plant traits is critical for predicting how diverse species respond to climate change. According to hydraulic and economic theories, leaves and roots—key organs for resource acquisition—are expected to function in coordination, such that species with faster resource utilization would possess leaf and root traits that facilitate rapid carbon, nutrient, and water uptake and fluxes. However, there has been limited evidence supporting leaf-root trait coordination and a role for that coordination on community structure. Here, we measured 13 leaf and root functional traits for 101 woody species from six tropical and subtropical forests, and assessed coordination and its association with community dominance. Hydraulic traits, such as leaf vein density and root vessel density, were coordinated between organs and showed compensation trade-offs between traits within organs, such as, leaf vein density and diameter. Economic traits relating to composition, such as nitrogen concentration, were coordinated between organs, whereas economic structural traits were decoupled, such as leaf mass per area and specific root length. Overall, hydraulic traits and economics traits were partially independent. The coordination of flux-related leaf and root traits was associated with ectomycorrhizal symbiosis and with dominance within the community. These findings indicate how trait organization within and across organs contributes to optimal whole plant function, with implications for performance in natural communities.
SMAC mimetics induce human macrophages to phagocytose live cancer cells
Authors: Liu Samantha Y. , Hulsman Max , Leyendecker Philipp , Chang Eugena , Donovan Katherine A. , Strobel Fabian , Dougan James , Fischer Eric S. , Dougan Michael , Dougan Stephanie K. , Qiang Li
Published: November 2024

Macrophages engulf apoptotic bodies and cellular debris as part of homeostasis, but they can also phagocytose live cells such as aged red blood cells. Pharmacologic reprogramming with the SMAC mimetic LCL161 in combination with T cell-derived cytokines can induce macrophages to phagocytose live cancer cells in mouse models. Here we extend these findings to encompass a wide range of monovalent and bivalent SMAC mimetic compounds, demonstrating that live cell phagocytosis is a class effect of these agents. We demonstrate robust phagocytosis of live pancreatic and breast cancer cells by primary human macrophages across a range of healthy donors. Unlike mouse macrophages where combination of SMAC mimetics with lymphotoxin enhanced phagocytosis, human macrophages were more efficiently polarized to phagocytose live cells by the combination of SMAC mimetics and IFNψ. We profiled phagocytic macrophages by transcriptional and proteomic methodologies, uncovering a positive feedback loop of autocrine TNFα production.
Covert muscle activity reveals dynamic freezing states and prepares the animal for action
Authors: Hobbiss Anna F. , Franco Mariana C. , Medeiros Alexandra M. , Rosher Charlie , Mendes César S. , Moita Marta A.
Published: November 2024

When an animal detects a threat it must make a split-second choice between fight, flight or freezing (1–3). During freezing, skeletal muscles sustain tension to maintain rigid, sometimes atypical postures, for many minutes at a time (4). Meanwhile the animal must dynamically assess its surroundings to plan future actions and ready its body for movement. The interplay between the neural and somatic systems during freezing remains poorly understood. Here we show that freezingDrosophila melanogasterdisplay a striking novel pattern of leg muscle activation unique to immobility, a rhythmic pulsing in the distal tibia. The muscle, which we show to be a previously undescribed leg accessory heart, displays multiple activity modes and ramps up to movement onset, implying a preparation for movement. The frequency of pulsing is dynamically modulated as the fly integrates external threat or safety cues, and artificially increasing pulse frequency leads to freezing breaks, indicating a causal role in the decision to move. Through the identification of a newDrosophilacardiac organ, this study provides a window into the multiple states which can underlie freezing behaviour, and the physiological changes which the body undergoes to ready the animal to move.
Inhibition of microtubule polymerization and dynein impairs the nuclear localization of the ependymoma-associated ZFTA-RELA fusion protein and NF-κB activation
Authors: Ishii Masaki , Suto Naoki , Katakawa Kazuaki , Makino Kosho , Toma-Fukai Sachiko , Sueki Shunsuke , Anada Masahiro , Kojima Hirotatsu , Ohata Shinya
Published: November 2024

Ependymomas are rare and chemotherapy-resistant gliomas. One subclass of supratentorial ependymomas, ST-EPN-ZFTA, expresses a fusion protein consisting of a nuclear protein, zinc finger translocation associated (ZFTA), andv-relreticuloendotheliosis viral oncogene homolog A (RELA), an effector transcription factor of the nuclear factor-κB (NF-κB) pathway (ZFTA-RELA). Constitutive localization of ZFTA-RELA to the nucleus hyperactivates the oncogenic NF-κB signaling pathway, thereby contributing to the pathogenesis of ST-EPN-ZFTA. To identify compounds that inhibit NF-κB activity induced by ZFTA-RELA, we established a high-throughput screening system using the NF-κB-responsive luciferase reporter cell line 6E8, which expresses ZFTA-RELA in a doxycycline-dependent manner. A chemical library of 9600 compounds selected for their structural diversity was screened, and a colchicine derivative was identified. Among colchicine and six of its derivatives, the IC50on ZFTA-RELA-dependent NF-κB-responsive luciferase activity in 6E8 cells was found to be the lowest for colchicine at 90 nM. Interestingly, microtubule polymerization inhibitors (colchicine and vinblastine) and dynein inhibitors (ciliobrevin D and dynarrestin) impaired ZFTA-RELA’s nuclear localization and NF-κB activity in 6E8 cells. These findings indicate that microtubule polymerization and dynein play pivotal roles in activating the NF-κB pathway in ST-EPN-ZFTA by promoting the nuclear localization of ZFTA-RELA. Consequently, inhibition of microtubule polymerization may be a therapeutic strategy for ST-EPN-ZFTA.
The effect of prolonged elbow pain and rTMS on cortical inhibition: A TMS-EEG study
Authors: Chowdhury Nahian S , Chang Wei-Ju , Cheng Donovan , Manivasagan Naveen , Seminowicz David A , Schabrun Siobhan M
Published: November 2024

Introduction

Recent studies using combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) have shown that pain leads to an increase in the N45 peak of the TMS-evoked potential (TEP), which is mediated by GABAergic inhibition. Conversely, 10Hz repetitive TMS (10Hz-rTMS), which provides pain relief, reduces the N45 peak. However, these studies used brief pain stimuli (lasting minutes), limiting their clinical relevance. The present study determined the effect of pain and 10Hz-rTMS on the N45 peak in a prolonged pain model (lasting several days) induced by nerve growth factor (NGF) injection to the elbow muscle.

Materials and Methods

Experiment 1: TEPs were measured in 22 healthy participants on Day 0 (pre-NGF), Day 2 (peak pain), and Day 7 (pain resolution).Experiment 2: We examined the effect of 5 days of active (n=16) or sham (n=16) rTMS to the left primary motor cortex (M1) on the N45 peak during prolonged NGF-induced pain, with TEPs measured on Day 0 and Day 4 (post-rTMS).

Results

Experiment 1:While no overall change in the N45 peak was seen, a correlation emerged between higher pain severity on Day 2 and a larger increase in the N45 peak.

Experiment 2: Active rTMS reduced the N45 peak on Day 4 vs. Day 0, with no effect in the sham group.

Conclusion

Our findings suggest that (i) higher pain severity correlates with an increase in the N45 peak, and (ii) rTMS decreases cortical inhibition in a model of prolonged experimental pain. This study extends previous research by demonstrating a link between pain perception and cortical inhibition within a prolonged pain context.
Rhamnogalacturonan-II dimerization deficiency impairs the coordination between growth and adhesion maintenance in plants
Authors: Baba Abu Imran , Lisica Lucija , Atakhani Asal , Aryal Bibek , Bogdziewiez Léa , Erguvan Özer , Heymans Adrien , Jewaria Pawan Kumar , Smith Richard S. , Bhalerao Rishikesh P. , Verger Stéphane
Published: November 2024

Cell adhesion is a fundamental feature of multicellular organisms. In plants, cell adhesion is mediated by the cell wall, but the control and maintenance of cell adhesion during growth and development remains poorly understood1. Here we uncover the role of a component of the cell wall, rhamnogalacturonan-II (RG-II) and its capacity to crosslink in the presence of Boron2, as a key regulator of plant cell adhesion maintenance. We show that RG-II dimerization deficiency leads to cell adhesion defects. Importantly, the analysis ofmur1mutants with RG-II dimerization defects uncovers a cell adhesion pathway that is distinct from that identified by the analysis of pectin deficient mutants3. We found that mutations in two cell wall integrity sensors, RESISTANCE TO FUSARIUM OXYSPORUM 1 and RECEPTOR-LIKE PROTEIN 44, as well as supplementation with the hormone brassinosteroid can partially rescue the adhesion defects associated with RG-II dimerization deficiency. We also show that adhesion defects associated with RG-II dimerization deficiency are related to increased epidermal tension as well as decreased homogalacturonan levels in the cell wall, which can also be rescued by supplementation with brassinosteroid. Overall, we propose that RG-II dimerization defects alter cell adhesion directly (reduced crosslinks) but also indirectly through cell wall integrity sensing, brassinosteroid signalling, cell wall remodelling and cell layer growth coordination. Thus, our results uncover the involvement of cell wall integrity sensors and hormonal signalling in the coordination between growth and adhesion maintenance in plants, which is a key feature for complex multicellularity.

Highlights

-

RG-II dimerization is required for cell-cell adhesion in plants.

-

Cell wall integrity sensors and brassinosteroid signalling mediate cell adhesion downstream of RG-II dimerization.

-

Cell detachments due to defective RG-II dimerization are caused by weakened middle lamella and higher tissue tension.
Cluster nanoarchitecture and structural diversity of PIEZO1 in intact cells
Authors: Verkest Clement , Roettger Lucas , Zeitzschel Nadja , Lechner Stefan G.
Published: November 2024

The mechanically activated ion channel PIEZO1 confers mechanosensitivity to many cell types and is thus essential for numerous physiological processes triggered by mechanical cues1–4. PIEZO1 channels assemble as propeller-shaped trimers5–7, which supposedly undergo a transition from a curved conformational state into a flattened state upon mechanical activation8–11. Whether this gating model also applies to PIEZO1 clusters and to what extent membrane curvature alters PIEZO1 conformation in living cells, is, however, still unclear. Here, we used MINFLUX nanoscopy to resolve the architecture of PIEZO1 clusters and demonstrate that PIEZO1 channels collectively deform the cell membrane into pit-shaped invaginations, which accommodate multiple channels and flatten in response to mechanical stimulation. Moreover, our data suggests that the deformability of the membrane and thus the conformation and sensitivity of PIEZO1 are altered by the architecture and the rigidity of the cytoskeleton. Together, our data provide previously unrecognized structural details about the subcellular distribution and the conformational variability of PIEZO1 in different cellular compartments, which challenge previously proposed hypotheses derived from studies of isolated channels and thus highlight the importance of examining PIEZO1 in its native environment, where additional factors contribute to channel function and structure.
BPMs regulate Arabidopsis seedling development by promoting auxin-independent degradation of the Aux/IAA protein IAA10
Authors: Ban Zhaonan , Hou Yueh-Ju , Ku Ellyse , Zhu YingLin , Hu Yun , Karadanaian Natalie , Zhao Yunde , Estelle Mark
Published: November 2024

After germination, seedlings undergo etiolated development (skotomorphogenesis), enabling them to grow towards the soil surface. In Arabidopsis, etiolated seedlings exhibit rapid hypocotyl elongation, apical hook formation and closed cotyledons to protect the meristem. In this study, we found that high-order mutants in theBPMgene family displayed defects in seedling development, characterized by a shorter hypocotyl, early apical hook opening, and opened cotyledons in the dark. BPM1, BPM2, BPM4, and BPM5 exhibit distinct expression patterns and subcellular localization in etiolated seedlings. In a hypocotyl segment assay thebpmmutants showed defects in auxin response indicating impaired auxin signaling in the hypocotyl. Expression of the auxin reporterDR5:GFPwas also altered in thebpm1,4,5mutant in various tissues compared to the wild type. Furthermore, we showed that BPM1 and IAA10 interact in yeast two-hybrid, BiFC, and Co-IP assays. Experiments in protoplasts indicated that BPM1 promotes ubiquitylation and degradation of IAA10, and the level of IAA10 protein is greater in thebpm1,4,5mutant. In addition, IAA10 over-expression resulted in phenotypes similar to thebpmmutants. These results indicate that the BPMs target the Aux/IAA proteins for ubiquitylation and degradation. Overall, our findings shed light on the key roles of the BPMs in auxin signaling during seedling development.
Identification of theStaphylococcus aureusEndothelial Cell Surface Interactome by Proximity Labeling
Authors: Rühling Marcel , Schmelz Fabio , Kempf Alicia , Paprotka Kerstin , Fraunholz Martin J.
Published: November 2024

Virulence strategies of pathogens depend on interaction with host cells. Binding and activation of receptors located on the plasma membrane is crucial for the attachment to or pathogen internalization by host cells. Identification of host cell receptors often is difficult and hence the identity of many proteins that play important roles during host-pathogen interaction remains elusive. We developed a novel proximity labeling approach, in which we decorated the opportunistic pathogenStaphylococcus aureuswith ascorbate peroxidase 2. Upon addition of hydrogen peroxide the peroxidase initiates proximity biotinylation ofS. aureushost receptors, thereby enabling identification of these proteins. We here demonstrate an endothelial cell surface interactome of 306 proteins of which neuronal adhesion molecule, protein tyrosine kinase PTK7, melanotransferrin, protein-tyrosine kinase Met, CD109 and others constitute novelS. aureusco-receptors. Filtering the interactome for validated surface proteins resulted in a list of 89 receptor candidates of which a 53% were described to interact withS. aureusor other pathogens.
Transcriptome of the murine duodenum during recovery after a lethal dose of total body irradiation
Authors: He Ling , Bhat Kruttika , Pajonk Frank
Published: November 2024

In the aftermath of 9/11, the radiobiology community sought novel radiation mitigators capable of preventing death when administered 24 hours or later after exposure to lethal ionizing radiation. The survival and expansion of normal stem cells are crucial for restoring tissue integrity in time to prevent mortality. While FDA-approved drugs for acute radiation syndrome primarily target the hematopoietic system, restoring the integrity of the intestinal lining is equally important for survival. However, the radiation response of the intestinal stem cell (ISC) population and its niche environment is not as well understood as that of the bone marrow. The aim of this study was to explore early transcriptomic changes in the small intestine after a lethal dose of total body irradiation (TBI), and during subsequent recovery.

C3H/Sed/Kam mice were irradiated with a TBI dose of 16 Gy, the published LD70/10. The compound 1-[(4-Nitrophenyl)sulfonyl]-4-phenylpiperazine (NSPP) was administered 24 hours post-irradiation. RNAs from the proximal duodenum were extracted at 28, 72, and 96 hours post-irradiation and subjected to RNA-sequencing. Differentially expressed genes were analyzed using gene-set enrichment analysis.

Radiation induced significant transcriptomic changes known to precede the death of lymphatic endothelial and epithelial cells. Upregulation ofLgr5+ISC gene signature was observed during recovery. NSPP treatment further amplified the activation of ISC-associated genes and other regenerative markers. Notably, genePsrc1showed strong activation throughout the recovery process, highlighting its potential role in this regenerative response. These findings suggest additional points of intervention for radiation mitigation in the intestines beyond targeting programmed cell death.
Local disorder is associated with enhanced catalysis in an engineered photoswitch
Authors: McCormick James W. , Dinan Jerry C. , Russo Marielle AX , Reynolds Kimberly A.
Published: November 2024

TheA. sativaLOV2 domain is commonly harnessed as a source of light-based regulation in engineered optogenetic switches. In prior work, we used LOV2 to create a light-regulated Dihydrofolate Reductase (DHFR) enzyme and showed that structurally disperse mutations in DHFR were able to tune the allosteric response to light. However, it remained unclear how light allosterically activates DHFR, and how disperse mutations modulate the allosteric effect. A mechanistic understanding of these phenomena would improve our ability to rationally design new light-regulated enzymes. We used a combination of Eyring analysis and CD spectroscopy to quantify the relationship between allostery, catalytic activity, and global thermal stability. We found that the DHFR/LOV2 fusion was marginally stable at physiological temperatures. LOV2 photoactivation simultaneously: (1) thermally destabilized the fusion and (2) lowered the catalytic transition free energy of the lit state relative to the dark state. The energetic effect of light activation on the transition state free energy was composed of two opposing forces: a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty. Allostery-tuning mutations in DHFR acted through this tradeoff, either accentuating the enthalpic benefit or minimizing the entropic penalty but never improving both. Many of the allostery tuning mutations showed a negative correlation between the light induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.
Exploring Neural Dynamics in the Auditory Telencephalon of Crows using Functional Ultrasound Imaging
Authors: Liao Diana A. , Schwarzbach Eva , Nieder Andreas
Published: November 2024

Crows, known for advanced cognitive abilities and vocal communication, rely on intricate auditory systems. While the neuroanatomy of corvid auditory pathways is partially explored, the underlying neurophysiological mechanisms are largely unknown. This study used functional ultrasound imaging (fUSi) to investigate sound-induced cerebral blood volume (CBV) changes in the field L complex of the crow’s auditory telencephalon, a functional analogue to the mammalian auditory cortex. FUSi revealed frequency-specific CBV responses, showing a tonotopic organization within the field L complex, with low frequencies in the posterior-dorsal region and high frequencies in the anterior-ventral region, similar to neuronal patterns reported in other songbirds. The responses were more robust when the crows were awake compared to when they were anesthetized. Machine learning analyses showed fUSi signals could be used to classify sound types accurately. Shorter stimuli reliably triggered transient CBV increases, while longer sounds resulted in variable responses, including negative deflections. This variability in CBV responses suggests a delineation of subregions within the field L complex with the central region (L2) as the primary processing hub and outer regions (L1, L3) integrating auditory information. These findings highlight the potential of fUSi for providing high-resolution insights into functional systems in corvids, enabling future exploration of task-related cognitive dynamics.
Population-based metaproteomics reveals functional associations between gut microbiota and phenotypes
Authors: Liang Shuang , Sun Yingying , Miao Zelei , Li Bang-yan , Xing Ziyuan , Xie Yuting , Cai Enci , Li Sainan , Liu Pu , Yang Min , Shuai Menglei , Gou Wanglong , Jiang Wenhao , Wang Youming , Gao Huanhuan , Zhang Ke , Yu Jing , Cai Xue , Wang Xingbing , Chen Yu-ming , Zheng Ju-Sheng , Guo Tiannan
Published: November 2024

The association between gut microbiota and physiological disorders underscores the crucial need to understand its largely unexplored biological functions. In this study, we analyzed 86,876 microbial proteins and 1,277 human proteins from 1,967 Chinese stool samples. Our results indicate that metaproteomic data captures the microbial biodiversity of a population more effectively than metagenomic data, displaying greater variability in microbial functions and providing reliable assessments of microbiota stability. We identified crucial functions of core microbes and discovered 10,714 associations between metaproteomic taxon, microbial function, or human proteins with 39 phenotypes, including 1,381 features related to Type 2 Diabetes (T2D). Importantly,Megasphaera elsdenii’s conversion of lactate to butyric acid appears to lower blood glucose levels, suggesting a protective mechanism against T2D. Our study underscores the power of population-based metaproteomics to offer unique functional insights into the gut microbiota.

Highlights

- The first large-scale population-based metaproteomics landscape.

- Metaproteomics efficiently maps microbial functions, exposing individual functional variation.

- 10,714 associations between metaproteomic taxa, microbial functions, or human proteins with 39 phenotypes.

-Megasphaera elsdeniiprotects against elevated blood glucose levels in the host by degrading lactate to produce butyric acid.
Mycobacterial methionine aminopeptidase type 1c moonlights as an anti-association factor on the 30S ribosomal subunit
Authors: Banerjee Aneek , Srinivasan Krishnamoorthi , Sengupta Jayati
Published: November 2024

Methionine aminopeptidase (MetAP), an essential metalloprotease, binds the 70S ribosome near the exit site of peptide tunnel and cleaves the N-terminal methionine from the nascent polypeptide chains. WhileE. coliexpresses a single subclass of type1 MetAP, mycobacteria possesses two subclasses, namely, MetAP1a and MetAP1c, differentiated by the presence of a 40 amino acid long N-terminal tether in the later. Here we reveal a yet unknown moonlighting role of MetAP1c in mycobacteria. We observe stationary phase-specific enhancement of expression and a unique 30S subunit affinity of MetAP1c. A 5Å cryo-EM map ofMycobacterium smegmatis(Msm) MetAP1c-30S subunit complex manifests for the first time the binding of MetAP1c at the inter-subunit side in the vicinity of proteins S13 and S19. MetAP1c binding and resulting conformational changes make the 30S subunit unfit for association with the 50S subunit, thereby conferring an anti-association property on MetAP1c. We further constructed two N-terminal mutants to establish the pivotal role of the N-terminal extension of MetAP1c in its moonlighting function.
One cannot have it all: trading-off ecosystem services and biodiversity bundles in landscape connectivity restoration
Authors: Margot Neyret , Daniel Richards , Marie-Caroline Prima , Etherington Thomas R. , Sandra Lavorel
Published: November 2024

Countering the impacts of habitat loss and fragmentation on ecosystems requires complementing conservation areas with Other Effective area-based Conservation Measures within landscapes to promote biodiversity and multiple ecosystem services (ES). However, critical knowledge gaps persist in where and how natural elements should be restored to improve landscape connectivity to simultaneously support, and reduce trade-offs between biodiversity and ES. In virtual landscape experiments that allow exploring the effects of spatial pattern systematically, we generated alternative landscape restoration scenarios aimed at fostering ecological connectivity. Scenarios varied in the location and size of restored areas complementing existing natural areas. We analysed the impact of these scenarios on four bundles representing distinct priorities of target ES and biodiversity-related values. As expected, all bundles were favoured by increasing restored area in the landscape, but they were promoted by different spatial configurations. Restoration scenarios that fostered high aggregation of natural habitats promoted biodiversity and cultural value-related bundles, while smaller natural elements dispersed throughout the landscape were more beneficial for the sustainable production and climate adaptation bundles. These contrasts were most pronounced at low restoration efforts, where landscape configuration had greatest impacts on biodiversity and ecosystem processes. Effective spatial planning of restoration initiatives within landscapes should consider these trade-offs, along with context-specific constraints, when prioritizing areas for restoration or conservation. Our findings contribute to a more comprehensive understanding of how protected and restored areas can be integrated within landscapes to jointly support connectivity for both biodiversity and people.

Highlights

Virtual landscape restoration options effects on four ecosystem services and biodiversity bundles

High aggregation of restored elements promotedbiodiversityandcultural value

Low aggregation promotedsustainable productionandclimate adaptation

These contrasts were most important at low restoration targets

These results highlight the importance of configuration trade-offs in restoration planning
A programmable, selection-free CRISPR interference system inStaphylococcus aureus
Authors: Miah Roni , Johannessen Mona , Kjos Morten , Lentz Christian S.
Published: November 2024

Common dCas9-based CRISPR interference (CRISPRi) system for gene regulation requires antibiotic selection and exogenous inducer molecules, posing significant challenges when applied inin vivobacterial infection models. UsingStaphylococcus aureusas a model organism, we have developed a programmable, plasmid-based, but selection-free (ppsf)-CRISPRi system that is based on the pCM29- plasmid which is stable without antibiotic selection. In this ppsf-CRISPRi system, dCas9 expression is regulated by an endogenous virulence gene promoter, and sgRNA expression is driven by a constitutive promoter eliminating the need for exogenous inducer molecules. The system was programmed to silence the expression of genes encoding the virulence factor coagulase or peptidoglycan hydrolase autolysin, whenever their respective endogenous promoter was activated. The selection-free functionality was confirmed over at least 27 generations and verified by qPCR and phenotypic assays depending on the protein target, including coagulation of rabbit plasma and THP-1 macrophage cell infectionin vitroas well asin vivoinfection ofGalleria mellonellalarvae, in each case phenocopying the observations made using transposon mutant strains. The system is suitable for long-term studies ofS. aureuspathogenesisin vitro orin vivoand represents a blueprint for the development of similar ppsf-CRISPRi systems in other bacterial species.
Rapid Semantic Processing: An MEG Study of Narrative Text Reading
Authors: Neklyudova Anastasia , Soghoyan Gurgen , Martynova Olga , Sysoeva Olga
Published: November 2024

Research has shown that semantic analysis occurs at early stages of word processing (less than 200 ms). While traditional studies have focused on isolated words/sentences, our research explores rapid semantic processing during reading stories using event-related potentials and magnetoencephalography. We employed the rapid serial visual presentation paradigm to present texts word by word. Each word presentation lasted 150 ms, enhancing rapid semantic processing. We computed semantic dissimilarity (SD) values for each word and categorized them into quartiles to investigate their effect on brain responses. Our analysis revealed significant ERP differences within early time windows (120-132 ms). Two distinct clusters were identified: positive in the right occipital region and negative in the left temporal region. In both clusters less pronounced responses were registered for words with lowest SD which corresponds to theories of predictive coding. These findings broaden our understanding of rapid semantic processing and suggest new methodology.
Loss of FIC-1-mediated AMPylation activates the UPRERand upregulates cytosolic HSP70 chaperones to suppress polyglutamine toxicity
Authors: Van Pelt Kate M. , Truttmann Matthias C.
Published: November 2024

Targeted regulation of cellular proteostasis machinery represents a promising strategy for the attenuation of pathological protein aggregation. Recent work suggests that the unfolded protein response in the endoplasmic reticulum (UPRER) directly regulates the aggregation and toxicity of expanded polyglutamine (polyQ) proteins. However, the mechanisms underlying this phenomenon remain poorly understood. In this study, we report that perturbing ER homeostasis inCaenorhabditis elegansthrough the depletion of either BiP ortholog,hsp-3orhsp-4,causes developmental arrest in worms expressing aggregation-prone polyQ proteins. This phenotype is rescued by the genetic deletion of the conserved UPRERregulator, FIC-1. We demonstrate that the beneficial effects offic-1knock-out (KO) extend into adulthood, where the loss of FIC-1-mediated protein AMPylation in polyQ-expressing animals is sufficient to prevent declines in fitness and lifespan. We further show that loss ofhsp-3andhsp-4leads to distinct, but complementary transcriptomic responses to ER stress involving all three UPRERstress sensors (IRE-1, PEK-1, and ATF-6). We identify the cytosolic HSP70 family chaperoneF44E5.4, whose expression is increased infic-1-deficient animals upon ER dysregulation, as a key effector suppressing polyQ toxicity. Over-expression ofF44E5.4, but not other HSP70 family chaperones, is sufficient to rescue developmental arrest in polyQ-expressing embryos uponhsp-3knock-down. Finally, we show that knock-down ofire-1,pek-1, oratf-6blocks the upregulation ofF44E5.4infic-1-deficient worms. Taken together, our findings support a model in which the loss of FIC-1-mediated AMPylation engages UPRERsignaling to upregulate cytosolic chaperone activity in response to polyQ toxicity.
Chemotagging: a chemogenetic approach for identifying cell types within vivocalcium imaging
Authors: Ko BumJin , Bacon Madeline E. , Zaki Yosif , Cai Denise J.
Published: November 2024

The ability to monitor the activity of specific cell typesin vivois critical for understanding the complex interplay between various neuronal populations driving freely moving behavior. Existing methods, such as optogenetic tagging (i.e., Optotagging1), have proven useful for identifying cell types inin vivoelectrophysiological recordings during freely moving behavior. However, electrophysiological recordings are limited in their capacity to track the same neuronal populations across long periods of time (days to weeks). Single-photon miniscope imaging offers the advantage of tracking the same cells across weeks to months; however, it is difficult to distinguish different cell types within the recorded population. Here, we present “chemotagging,” a technique that allows for the identification of specific cell types inin vivocalcium imaging recordings. This protocol offers a method for tagging cell types with chemogenetic tools like Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)2, while simultaneously recording calcium activity from a pan-neuronal population with calcium indicators. We highlight the key advantages and limitations of chemotagging and its potential implications for neuroscience research.
Synergistic Behavioral and Neuroplastic Effects of Psilocybin-NMDAR Modulator Administration
Authors: Ben-Tal Tom , Pogodin Ilana , Botvinnik Alexander , Lifschytz Tzuri , Heresco-Levy Uriel , Lerer Bernard
Published: November 2024

The full therapeutic potential of serotonergic psychedelics (SP) in treating neuropsychiatric disorders, such as depression and schizophrenia, is limited by possible adverse effects, including perceptual disturbances and psychosis, which require administration in controlled clinical environments. This study investigates the synergistic benefits of combining psilocybin (PSIL) with N-methyl-D-aspartate receptor (NMDAR) modulators D-serine (DSER) and D-cycloserine (DCS) to enhance both efficacy and safety. Using ICR male mice, we examined head twitch response (HTR), MK-801-induced hyperlocomotion, and neuroplasticity related synaptic protein levels in the frontal cortex, hippocampus, amygdala, and striatum. Our results indicate that PSIL significantly increased HTR—a surrogate measure for hallucinogenic effects—which was reduced by the co-administration of DSER or DCS in a dose-dependent manner. Similarly, combining PSIL with DSER or DCS significantly decreased MK-801-induced hyperactivity, modeling antipsychotic effects. Neuroplasticity-related synaptic protein assays demonstrated that the PSIL-DSER combination enhanced GAP43 expression over all 4 brain examined and overall expression of the 4 assayed synaptic proteins in the hippocampus, while PSIL-DCS elevated PSD95 levels across all 4 brain regions, suggesting a synaptogenic synergy. These findings support the hypothesis that combinations of SP with NMDAR modulators could optimize the therapeutic potential of SP by mitigating adverse effects and enhancing neuroplasticity. Future studies should focus on refining administration protocols and evaluating translational applicability for broader clinical use.
Dorsolateral prefrontal cortex drives strategic aborting by optimizing long-run policy extraction
Authors: Noel Jean-Paul , Zhang Ruiyi , Pitkow Xaq , Angelaki Dora E.
Published: November 2024

Real world choices often involve balancing decisions that are optimized for the short-vs. long-term. Here, we reason that apparently sub-optimal single trial decisions in macaques may in fact reflect long-term, strategic planning. We demonstrate that macaques freely navigating in VR for sequentially presented targets will strategically abort offers, forgoing more immediate rewards on individual trials to maximize session-long returns. This behavior is highly specific to the individual, demonstrating that macaques reason about their own long-run performance. Reinforcement-learning (RL) models suggest this behavior is algorithmically supported by modular actor-critic networks with a policy module not only optimizing long-term value functions, but also informed of specific state-action values allowing for rapid policy optimization. The behavior of artificial networks suggests that changes in policy for a matched offer ought to be evident as soon as offers are made, even if the aborting behavior occurs much later. We confirm this prediction by demonstrating that single units and population dynamics in macaque dorsolateral prefrontal cortex (dlPFC), but not parietal area 7a or dorsomedial superior temporal area (MSTd), reflect the upcoming reward-maximizing aborting behavior upon offer presentation. These results cast dlPFC as a specialized policy module, and stand in contrast to recent work demonstrating the distributed and recurrent nature of belief-networks.
Variable temperature studies of tetrapyridinesilver(I) hexafluorophosphate and tetrapyridinesilver(I) hexafluoroantimonate
Authors: McNelly Alice G. , Christensen Kirsten E. , Thompson Amber L.
Published: November 2024

As part of a larger study into phase transitions, the structures of tetrapyridinesilver(I) hexafluorophosphate, [Ag(C5H5N)4](PF6) or AgPy4PF6, and tetrapyridinesilver(I) hexafluoroantimonate, [Ag(C5H5N)4](SbF6) or AgPy4SbF6, were determined at 300 and 100 K from single-crystal X-ray diffraction. The compounds are isostructural, crystallizing in the space group I\overline{4} with Z′ = 1/4. Over the temperature range studied no evidence of a phase change was found. The dihedral angles between the pyridine rings are compared with similar cations from the literature and discussed.
Syntheses and crystal structures of the imides 4-(2-phenylethyl)- and 4-[2-(4-hydroxyphenyl)ethyl]-4-azatetracyclo[5.3.2.02,6.08,10]dodec-11-ene-3,5-dione
Authors: Bajko Jonathan P. , Staples Richard J. , Biros Shannon M.
Published: November 2024

The syntheses and characterization (NMR and XRD) of two substituted [2.2.2]bicyclooctene ring systems are described here. The cyclohexene rings of these systems adopt a nearly perfect boat conformation according to analysis using Cremer–Pople parameters. Both structures contain a nearly planar imide ring that is oriented endo relative to a bridgehead cyclopropyl ring. 4-(2-Phenylethyl)-4-azatetracyclo[5.3.2.02,6.08,10]dodec-11-ene-3,5-dione, C19H19NO2, is substituted with a phenylethyl group that hosts C—H...π interactions in the crystal. 4-[2-(4-Hydroxyphenyl)ethyl]-4-azatetracyclo[5.3.2.02,6.08,10]dodec-11-ene-3,5-dione, C19H19NO3, bears a 4-hydroxyphenylethyl group on the imide ring and contains O—H...O and C—H...O hydrogen bonds.
Comprehensive structural study of lanthanide(III) chloride hydrates: [RECl3·xH2O (RE = La–Nd, Sm–Lu; x = 6, 7)]
Authors: Kandabadage Thimira , Legnon Beau , Baranets Sviatoslav
Published: November 2024

A comprehensive crystallographic study is presented of the complete series of rare-earth(III) chloride hydrates. Early lanthanides form dimeric [(H2O)7
RE(μ-Cl)2
RE(H2O)7]4+ binuclear complexes in which each RE atom (RE = La3+, Ce3+) is coordinated by seven H2O molecules and two bridging inner-sphere chloride ions. Di-μ-chlorido-bis[heptaaqualanthanide(III)] tetrachloride, [(H2O)7
RE(μ-Cl)2
RE(H2O)7]Cl4, crystallizes in the triclinic space group P
1. Heavier lanthanides exhibit monomeric [RECl2(H2O)6]+ units where each RE atom (RE = Pr3+, Nd3+, Sm3+–Lu3+) is coordinated by six H2O molecules and two inner-sphere chloride ions. Hexaaquadichloridolanthanide(III) chlorides, [RECl2(H2O)6]Cl, adopt the monoclinic space group P2/c. In both structures, the cationic inner-sphere complex is counter-charged by the corresponding number of outer-sphere Cl− anions, in which the metal ion and outer-sphere chloride ion lie on crystallographic twofold axes. Crystal structures for all compounds were determined in high quality with refined H-atom positions and were collected at the same temperature (100 K), providing a uniform structural dataset and addressing discrepancies in previous reports. The crystal structure of [HoCl2(H2O)6]Cl is reported for the first time.
The revival of the ancient technique of pounding spices for contemporary cooking by Zilli’s
Authors: Vyas Pallavi Ghanshyala
Published: November 2024

Learning outcomes

After reading and discussing the case, the students will be able to: apply paid, owned and earned digital marketing tools to Zilli’s, analyze the omnichannel and e-commerce strategy of Zilli’s, evaluate digital marketing strategy of Zilli’s and elaborate resources available to Zilli’s in the context of emerging markets.

Case overview/synopsis

Anubhav Bhatnagar founded Zilli’s – The Spice Company to bring grandma’s recipes to modern kitchens. This case study chronicles the growth and challenges faced by the company. Zilli’s philosophy relied on hand-pounding spices, which retained their aromatic signature, flavor intensity, nutritional value and cultural importance better than their commercially processed counterparts. Bhatnagar started his business during the lockdown. The founder aimed to produce spices that were free of preservatives and had long-lasting aromas. His kitchen trials demonstrated that hand-pounded spice powders simplified cooking and improved flavor. Direct manufacturer ties and a Hyderabad production plant managed by local rural women enabled the firm to expand to India and a few neighboring markets. Zilli’s growth was slow due to heavy competition from well-known brands. E-commerce was Zilli’s only viable option. The prospect sounded great, but the company needed to strategize differently to build an effective digital marketing strategy. Marketing and sales of Zilli’s products presented various constraints as it was difficult to convince consumers of Zilli’s products’ authenticity, quality and pricing. Many retail outlets and e-commerce platforms already sold numerous competitor’s products. The company’s aspiration to establish a global footprint could be hampered by low consumer acceptance of Zilli’s goods due to its limited reach. Thus, Bhatnagar sought digital marketing tactics to promote Zilli’s products and create brand awareness and recall for his spice powders in the competitive spice powder category. This case requires the reader to debate, analyze and propose digital marketing strategies to boost Zilli’s product visibility, acceptability and sales. The readers could identify gaps in Zilli’s existing digital marketing strategy and offer suggestions to Zilli’s for increasing spice powder sales in the online marketplace.

Complexity academic level

This case study applies to a postgraduate-level management course.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 8: Marketing.
Inquisitive case of Paytm buyback
Authors: Agarwal Manish , Kandi V.S. Prasad
Published: November 2024

Learning outcomes

After completion of the case study, the students will be able to assess Paytm’s share buyback in the context of conventional practices, especially for loss-making firms, analyze the influence of initial public offering (IPO) performance on market sentiments and the role of subsequent events in shaping investor confidence, explore the regulatory framework for share buybacks in India and its impact on Paytm’s decision, scrutinize Paytm’s post-IPO financials and evaluate the board’s rationale for the share buyback and examine the factors influencing Paytm shareholders’ decisions amid the buyback, considering market conditions and the company’s outlook.

Case overview/synopsis

This case study discusses the unorthodox choice made by Paytm, a leading Indian digital payments and financial services provider, to begin a share repurchase program just one year after its substantial IPO. Paytm encountered difficulties as its stock price experienced a sharp decline of 74% following the IPO, which raised concerns among shareholders and elicited mistrust from analysts. This case study explores the reasoning for the buyback, the legislative framework of share buybacks in India and the diverse viewpoints of analysts regarding the company’s financial strategy. This case study provides not only ample opportunity to discuss ethical issues around managers’ corporate actions but also brings investors a dilemma.

Complexity academic level

This case study is suited to Master of Business Administration/Master of Science/Bachelor of Business Administration/Bachelor of Science.