bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel male accessory gland peptide reduces female post-mating receptivity in the brown planthopper
Authors: Zhang Yi-Jie , Zhang Ning , Bu Ruo-Tong , Nässel Dick R. , Gao Cong-Fen , Wu Shun-Fan
Published: October 2024

Mating in insects commonly induces a profound change in the physiology and behavior of the female that serves to secure numerous and viable offspring and to ensure paternity for the male by reducing receptivity of the female to further mating attempts. Here, we set out to characterize the post-mating response (PMR) in a pest insect, the brown planthopper (BPH)Nilaparvata lugensand to identify a functional analog of sex peptide (SP) and/or other seminal fluid factors that contribute to the PMR inDrosophila. We find that BPHs display a distinct PMR that lasts for about 4 days and includes a change in female behavior with decreased receptivity to males and increased oviposition. Extract from male accessory glands (MAG) injected into virgin females triggers a similar PMR, lasting about 24h. Since SP does not exist in BPHs, we screened for candidate mediators by performing a transcriptional and proteomics analysis of MAG extract. We identified a novel 51 amino acid peptide present only in the MAG and not in female BPHs. This peptide, that we designate maccessin (macc), affects the female PMR. Females mated by males withmaccknockdown display receptivity to wild type males in a second mating, which does not occur in controls. However, oviposition is not affected. Injection of recombinant macc reduces female receptivity, with no effect on oviposition. Thus, macc is so far the only candidate seminal fluid peptide that promotes a PMR in BPHs. Our analysis suggests that the gene encoding the macc precursor is restricted to species closely related to BPHs.

Author summary

In insects, mating often induces a long-lasting change in the female behavior and physiology, called a post-mating response (PMR). This ensures numerous and viable offspring, but also serves to secure paternity for the male by inhibiting the female receptivity to further mating attempts. Here, we demonstrate that a pest insect, the brown planthopper (BPH)Nilaparvata lugens, also displays a PMR with decreased receptivity to further mating and increased egg laying. We furthermore find that seminal fluid extracted from the male accessory gland of BPHs injected into females generates a PMR. Next, we identified a novel peptide unique to the male accessory gland (designated maccessin) and demonstrate that this peptide is responsible for the reduced receptivity in the PMR, but does not affect egg laying. The gene encoding maccessin appears unique to close relatives ofN. lugens. This is similar to aDrosophilamale accessory gland factor, sex peptide, which is known to induce a PMR, and occurs only in a limited number ofDrosophilaspecies.
Domain-specific Schema Reuse Supports Flexible Learning to Learn in Primate Brain
Authors: Tian Kaixi , Zhao Zhiping , Chen Yang , Ge Ningling , Cao Shenghao , Han Xinyong , Gu Jianwen , Yu Shan
Published: October 2024

Prior knowledge accelerates subsequent learning of similarly structured problems - a phenomenon termed “learning to learn” - by forming and reusing generalizable neural representations, i.e., the schemas. However, the stability-plasticity dilemma, i.e., how to exploit stable schemas to facilitate learning while remaining flexible towards possible changes, is not well understood. We hypothesize that restricting schemas to specific functional, e.g., decision-making, subspace and making it orthogonal to other subspaces allows the brain to balance stability and plasticity. To test it, we trained three macaques on visuomotor mapping tasks and recorded neural activity in the dorsolateral premotor cortex. By delineating decision and stimulus subspaces, we identified a schema-like manifold within only the decision subspace. The reuse of decision schemas significantly facilitated subsequent learning. In addition, the decision subspace exhibited a trend to be orthogonal to the stimulus subspace, minimizing interference between these two domains. Our results revealed that restricting schemas to specific functional domains can preserve useful knowledge while maintaining orthogonality with other subspaces, allowing for flexible adaptation to new environments, thereby resolving the stability-plasticity dilemma. This finding provides new insights into the mechanisms underlying brain’s capability to learn both fast and flexibly, which can also inspire more efficient learning algorithms for artificial intelligence systems towards working in open, dynamic environments.
Foxi1 regulates multiple steps of mucociliary development and ionocyte specification through transcriptional and epigenetic mechanisms
Authors: Bowden Sarah , Brislinger-Engelhardt Magdalena Maria , Hansen Mona , Temporal-Plo Africa , Weber Damian , Hägele Sandra , Lorenz Fabian , Litwin Tim , Kreutz Clemens , Walentek Peter
Published: October 2024

Foxi1 is a master regulator of ionocytes (ISCs / INCs) across species and organs. Two subtypes of ISCs exist, and both α- and β-ISCs regulate pH- and ion-homeostasis in epithelia. Gain and loss of FOXI1 function are associated with human diseases, including Pendred syndrome, male infertility, renal acidosis and cancers. Foxi1 functions were predominantly studied in the context of ISC specification, however, reports indicate additional functions in early and ectodermal development. Here, we re-investigated the functions of Foxi1 inXenopus laevisembryonic mucociliary epidermis development and found a novel function for Foxi1 in the generation of Notch-ligand expressing mucociliary multipotent progenitors (MPPs). We demonstrate that Foxi1 has multiple concentration-dependent functions: At low levels, Foxi1 confers ectodermal competence through transcriptional and epigenetic mechanisms, while at high levels, Foxi1 induces a multi-step process of ISC specification and differentiation. We further describe howfoxi1expression is affected through auto- and Notch-regulation, how Ubp1 and Dmrt2 regulate ISC subtype differentiation, and how this developmental program affects Notch signaling as well as mucociliary patterning. Together, we reveal novel functions for Foxi1 inXenopusmucociliary epidermis formation, relevant to our understanding of vertebrate development and human disease.
Fibroblast activation protein defines aggressive EMT-associated cancer cell state and prognosis in localized ccRCC
Authors: Pellinen Teijo , Luomala Lassi , Mattila Kalle E , Hemmes Annabrita , Välimäki Katja , Brück Oscar , Paavolainen Lassi , Kankkunen Elisa , Nisén Harry , Järvinen Petrus , Castillon Leticia , Vanharanta Sakari , Vainio Paula , Kallioniemi Olli , Jaakkola Panu M. , Mirtti Tuomas
Published: October 2024

Despite being highly vascularized and immune-rich, the prognostic impact of immune infiltration and tumor microenvironment heterogeneity in localized clear cell renal cell carcinoma (ccRCC) remains unclear. Using 33-marker immunofluorescence imaging, we analyzed spatial distributions in 1,728 tissue cores from 435 localized ccRCC cases. Higher CD45⁺ infiltration correlated with worse survival, establishing CD45⁺ density as a prognostic marker. In CD45hightumors, ccRCC cells losing epithelial markers showed increased expression of mesenchymal markers such as fibroblast activation protein (FAP), secreted protein acidic and rich in cysteine (SPARC), vimentin (VIM), and PD-L1, indicating epithelial-to-mesenchymal transition (EMT). The FAP⁺EMT⁺ state further stratified CD45highpatients toward poorer outcomes and was associated with immunosuppressive elements, including M2 macrophages, exhausted and regulatory T cells, and FAP⁺ cancer-associated fibroblasts. Our study identifies high CD45⁺ infiltration and a FAP⁺EMT⁺ cancer cell state as indicators of poor survival in localized ccRCC, highlighting their potential to refine patient stratification and guide immuno-oncology treatment strategies.
DDO-adjuvanted influenza A virus nucleoprotein mRNA vaccine induces robust humoral and cellular type 1 immune responses and protects mice from challenge
Authors: Gnazzo Victoria , Saleh Hanaa , Castro Ítalo , Boon Adrianus C.M. , Pinto Amelia K , Brien James D. , López Carolina B.
Published: October 2024

A challenge in viral vaccine development is to produce vaccines that generate both neutralizing antibodies to prevent infection and cytotoxic CD8+T-cells that target conserved viral proteins and can eliminate infected cells to control virus spread. mRNA vaccines offer an opportunity to design vaccines based on conserved CD8-targeting epitopes, but achieving robust antigen-specific CD8+T-cells remains a challenge. Here we tested the viral-derived oligonucleotide DDO268 as an adjuvant in the context of a model influenza A virus (IAV) nucleoprotein (NP) mRNA vaccine in C57BL/6 mice. DDO268 safely induced local type I interferon (IFN) production, stimulated dendritic cells type 1 (DC1) activation and migration to the draining lymph nodes, and improved the generation of IgG2c antibodies and antigen-specific effector Th1 CD4+and CD8+T-cells (IFNγ+TNFα+IL2+) when co-packaged with NP mRNA. The DDO268 adjuvanted vaccine provided enhanced protection against lethal IAV challenge and reduced the antigen dose required to achieve this protection. These results highlight the potential of DDO268 as an effective mRNA vaccine adjuvant and show that an IAV NP mRNA/DDO268 vaccine is a promising approach for generating protective immunity against conserved IAV epitopes.

IMPORTANCE

Vaccines that generate neutralizing antibodies and cytotoxic CD8+T-cells targeting conserved epitopes are ideal for effective protection against viruses. mRNA vaccines combined with the right adjuvant offer a promising solution to this challenge. We show that the virus-derived oligonucleotide DDO268 enhances antibody and T cell responses to an influenza A virus (IAV) nucleoprotein (NP) mRNA vaccine in mice. DDO268 safely induces local type I interferon production and stimulates dendritic cell activation providing enhanced protection against IAV challenge. In addition, the adjuvant activity of DDO268 allows for the use of lower antigen doses during vaccination.
VAPOR: Variational autoencoder with transport operators decouples co-occurring biological processes in development
Authors: Sheng Jie , Wang Daifeng
Published: October 2024

Background

Emerging single-cell and spatial transcriptomic data enable the investigation of gene expression dynamics of various biological processes, especially for development. To this end, existing computational methods typically infer trajectories that sequentially order cells for revealing gene expression changes in development, e.g., to assign a pseudotime to each cell indicating the ordering. However, these trajectories can aggregate different biological processes that cells undergo simultaneously–such as maturation for specialized function and differentiation into specific cell types–which do not occur on the same timescale. Therefore, a single pseudotime axis may not distinguish gene expression dynamics from co-occurring processes.

Methods

We introduce a method, VAPOR (variational autoencoder with transport operators), to decouple dynamic patterns from developmental gene expression data. Particularly, VAPOR learns a latent space for gene expression dynamics and decomposes the space into multiple subspaces. The dynamics on each subspace are governed by an ordinary differential equation model, attempting to recapitulate specific biological processes. Furthermore, we can infer the process-specific pseudotimes, revealing multifaceted timescales of distinct processes in which cells may simultaneously be involved during development.

Results

Initially tested on simulated datasets, VAPOR effectively recovered the topology and decoupled distinct dynamic patterns in the data. We then applied VAPOR to a developmental human brain scRNA-seq dataset across postconceptional weeks and identified gene expression dynamics for several key processes, such as differentiation and maturation. Moreover, our benchmarking analyses also demonstrated the outperformance of VAPOR over other methods. Additionally, we applied VAPOR to spatial transcriptomics data in the human dorsolateral prefrontal cortex. VAPOR captured the ‘inside-out’ pattern across cortical layers, potentially revealing how layers were formed, characterized by their gene expression dynamics.

Conclusion

VAPOR is open source for general use (https://github.com/daifengwanglab/VAPOR) to parameterize and infer developmental gene expression dynamics. It can be further extended for other single-cell and spatial omics such as chromatin accessibility to reveal developmental epigenomic dynamics.
Ribosomal Biogenesis Hyperactivation and ErbB signalling Mediated Network Rewiring Causes Adaptive Resistance to FGFR2 Inhibition
Authors: Zhang Tao , Shin Sung-Young , McCrimmon Callan , Theocharous Mandy , Schittenhelm Ralf B , Jarde Thierry , Daly Roger J , Nguyen Lan K
Published: October 2024

Fibroblast Growth Factor Receptor 2 inhibition presents a promising therapeutic approach for restraining the growth and survival of cancer cells, particularly in breast tumours. However, the emergence of resistance to FGFR2 inhibitors like PD173074 highlights the importance of understanding the molecular mechanisms driving resistance and identifying effective therapeutic strategies. In this study, we employed temporal quantitative proteomics and phosphoproteomics, complemented by computational clustering, PTM-SEA analysis, and kinase activity prediction, to monitor the response of MFM223 triple negative breast cancer cells to FGFR2 inhibition. Strikingly, we observed a marked enrichment of ribosome biogenesis function modules immediately following treatment, a phenomenon not observed with other inhibitors. Additionally, we discovered that CX-5461, an RNA polymerase I inhibitor, synergistically enhanced the growth inhibition induced by PD173074, mechanistically attributed to its significant suppression of rDNA transcription stimulated by PD173074. Moreover, our phosphoproteomics dynamic profiling identified the clustering of kinases within MAPK and ErbB signalling pathways, indicative of their reactivation in response to FGFR2 inhibition. Experimentally validating this finding, we observed a notable rebound in phosphorylation levels of key kinases such as ERK1/2 and ErbB3, and demonstrated a substantial synergistic effect of PD173074 in combination with Trametinib, a MEK inhibitor, in suppressing cancer cell growth. Collectively, our findings provide critical insights into the network rewiring triggered by FGFR2 inhibition and offer a foundation for the rational design of combinatorial therapeutic strategies to overcome resistance mechanisms associated with FGFR2 inhibitors.
Preliminary Findings from an Augmented Reality (AR) App Delivering Recovery-Oriented Cognitive Therapy for Negative Symptoms in Schizophrenia
Authors: Tang Sunny X. , Foroughi Moein , Brinen Aaron P. , Birnbaum Michael L. , Berretta Sarah , Behbehani Leily M. , Kane John M. , Yoon Edward , Cronin William F.
Published: October 2024

Background

Negative symptoms are a primary driver of poor outcomes in schizophrenia spectrum disorders (SSD), but there are no FDA-approved medications or FDA-cleared therapeutics targeting negative symptoms in schizophrenia. NST-SPARK is a novel digital therapeutic targeting negative symptoms in SSD. It is a smartphone application delivering recovery-oriented cognitive therapy (CT-R), via gamified augmented reality (AR) experiences, to provide experiential learning aimed at dismantling maladaptive beliefs. In this study, we assessed a prototype (NST-SPARK v.1.5) in 20 participants with SSD and clinically significant negative symptoms. NST-SPARK v.1.5 delivers a single therapeutic module over a 1-week period. The primary objective was to determine the acceptability and feasibility of this approach. Secondary objectives were to generate descriptive findings for changes in defeatist beliefs, self-esteem, and attitudes toward goal-oriented activities.

Methods

Recruitment and all study procedures were completed online. Twenty participants with schizophrenia or schizoaffective disorder were enrolled, with a range of demographic and socioeconomic status and treatment settings. Participants completed self-reports on the acceptability and feasibility of NST-SPARK v.1.5 and provided open-ended feedback through a semi-structured interview. Self-report scales on defeatist beliefs, self-esteem, and attitudes toward goal-oriented activities were completed before and after participants were introduced to NST-SPARK, and then again at a 1-week follow-up.

Results

In general, participants found NST-SPARK v.1.5 to be feasible and acceptable, responding with an average response of “Agree”, indicating that the intervention was found to meet with the participants’ approval and seemed implementable. Almost all participants (19 of 20) used the app on their own prior to the 1-week follow up despite not being incentivized to do so. In addition, participants responded to open-ended feedback questions in a generally positive way. We also observed shifts in defeatist beliefs (Cohen’s d = 0.12), self-esteem (Cohen’s d = -0.21), and attitudes toward goal attainment consistent (intention: Cohen’s d = 0.13; confidence: Cohen’s d = 0.35) with intended improvements in these targeted areas. Participants were able to make substantive progress toward identified goals in 90% of cases.

Conclusions

This preliminary, single-arm, unblinded study of a single-module prototype for NST-SPARK found that the approach is generally acceptable and feasible for people with SSD and negative symptoms. Engagement of the intended target of defeatist beliefs was supported by our findings but require confirmation in future randomized controlled trials. Overall, NST-SPARK is based on a promising approach and further development is warranted.
TaxonGPT: Taxonomic Classification Using Generative Artificial Intelligence
Authors: Huang Haoyuan , Li Teng , Wang Zhixuan , Seldon David , Rodrigo Allen
Published: October 2024

To address the challenges of consistency and quality in taxonomic classifications, we have developed a Python program called TaxonGPT, that utilizes the natural language processing capabilities of generative artificial intelligence (gAI, specifically, ChatGPT-4o) to generate taxonomic descriptions and taxonomic keys. To counter the propensity for large language model gAIs to “hallucinate”, we use knowledge graph semantic representation and an error-checking module to ensure that accurate taxonomic descriptions and keys are obtained. In this paper, we describe how TaxonGPT embeds ChatGPT-4o’s responses as outputs. We also report on benchmark tests for accuracy, efficiency and reproducibility. These tests demonstrate that TaxonGPT excels in generating taxonomic keys and descriptions.
Mesial-to-lateral patterns of epileptiform activity identify the seizure onset zone in mesial temporal lobe epilepsy
Authors: Aguila Carlos A. , Lucas Alfredo , Lavelle Sarah , Pattnaik Akash R. , Kim Juri , Ojemann William K.S. , Ma Devin , Josyula Mariam , Petillo Nina , LaRocque Joshua J. , Sinha Saurabh R. , Ellis Colin A. , Parashos Alexandra , Gleichgerrcht Ezequiel , Davis Kathryn A. , Litt Brian , Conrad Erin C.
Published: October 2024

Mesial temporal lobe epilepsy (mTLE) is a common localization of drug-resistant epilepsy in adults. Patients often undergo intracranial EEG (iEEG) monitoring to confirm localization and determine candidacy for focal ablation or resection. Clinicians primarily base surgical decision-making on seizure onset patterns, with imaging abnormalities and information from interictal epileptiform discharge (spikes) used as ancillary data. How the morphology and timing of spikes within multi-electrode sequences may inform surgical planning is unknown, in part due to the lack of measurement methods for large datasets. We hypothesized that patients with mTLE have a distinct mesial-to-lateral spike pattern that differentiates them from other epilepsy localizations. In a multicenter study at the University of Pennsylvania and the Medical University of South Carolina, we analyzed the timing and morphology of spikes and seizure high frequency energy ratio (HFER) in 75 patients with drug-resistant epilepsy. We compared these features across patients with mTLE, temporal neocortical epilepsy, and other localizations. A logistic regression model combining all features predicted a clinical localization of mTLE in unseen patients with an AUC of 0.82 (compared to an AUC of 0.70 for seizure-only features, DeLong’s testp= 0.08). Spike rate was the most important feature in the combined model. Modeled probability of mTLE was similar between patients who had a good versus a poor 12-month outcome after undergoing a mesial temporal resection or ablation (p= 0.34). These findings support quantitative spike analysis to supplement analysis of seizures for use in surgical planning.
Evaluating the environmental impact of clinical research: a life-cycle analysis of a French academic randomised clinical trial
Authors: Fougerou-Leurent Claire , Forteau Louise , Perrot-Loyer Maëlle , Renault Alain , Mouchel Catherine , Rousseau Chloe , Marion Enora , Cochennec Sabrina , Ganivet Anne , Gervais Marie-Laure , Fin Loïc , Laviolle Bruno
Published: October 2024

Objectives

To assess the environmental impact of an academic clinical trial, by adapting the life-cycle analysis methodology to clinical research.

Design

A retrospective, simplified complete life-cycle analysis (LCA), according to the EF 3.0 methodology. LCA is a standardised (ISO14040/44) method for assessing the environmental impacts of a product over its entire life cycle on several environmental issues. It is the balance of inputs and releases associated with the process, from conception to end-of-life.

Setting

A prospective, double-blind, randomised controlled trial in neurosurgery. The trial included 202 patients in 18 university hospitals across France.

Participants

Not applicable

Intervention

Not applicable

Main outcome measures

Fourteen impact indicators that could be combined into a single score, for the identification of hotspots of interest.

Results

Climate change (or greenhouse gas emissions), was the most important indicator, accounting for almost 30% of the single score. Greenhouse gas emissions were estimated at 31.6 tons of carbon dioxide equivalent. This was followed by the depletion of abiotic resources - fossil fuels (24%), resource use - minerals and metals (12%), and particulate matter emissions (8%). The main hotspots identified were patient’ transport and clinical research assistant travel for source data verification.

Conclusions

By using complete LCA approach, our study confirms that conducting a clinical trial has a significant environmental impact, particularly on climate change. The main identified hotspots were related to the transport of patients and clinical research assistants

ARTICLE SUMMARY

Strengths and limitations of this study

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This study describes the first complete life-cycle analysis of a clinical trial

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Fourteen environmental factors were assessed, appraising all trial activities, from conception to close-out

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This study complements those previously published in the process of establishing eco-design as a new paradigm for clinical research

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Only one clinical trial was assessed, limiting the transposability of the conclusions

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Due to the lack of published impact data for some activities, assumptions had to be made to estimate their environmental impact
Proteome-wide and mendelian randomisation analyses of chronic widespread pain: diagnosis, prognosis, and drug target discovery
Authors: Chen Li , Kelleher Eoin , Meng Ruogu , Liu Duanke , Guo Yuchen , Wang Yunhe , Gao Yaoqing , Huang Zhe , Liang Zhu , Yuan Shuai , Zeng Chao , Lei Guanghua , Ma Jun , Dong Yanhui , Irani Anushka , Xie Junqing , Prieto-Alhambra Daniel
Published: October 2024

Chronic widespread pain (CWP) remains challenging due to its heterogenous causes and complex mechanisms. We analysed 2,923 plasma proteins from 29,254 UK Biobank participants. We first identified 811 proteins correlated with the presence of CWP cross- sectionally. We then created a sparse (top 10 proteins) and intricate (all significant proteins) proteomic-based score (ProtS) for CWP, both outperforming and improving the traditional clinical score (AUC: 0.82 and 0.88 vs 0.81 individually, and 0.87 and 0.92 in combination). Prospectively, the ProtS was associated with increased risks of a spectrum of pain traits, including dimensions from pain onset, progression and intensity, up to 13-years of follow-up; More importantly, we identified distinct proteomic signatures for nociplastic pain compared to nociceptive and neuropathic pain. For the individual proteins, carbonic anhydrase 14 (CA14) and leptin appeared as promising casual CWP biomarkers as triangulated by Mendelian randomisation and colocalization analyses. Lastly, our drug-repurposing analysis identified ten potential candidates for CWP therapies, calling for further research including randomised controlled trials. Although no CA14 agonists are currently available, CA14 remains a promising target, warranting further efforts to explore its role in pain modulation.
Antisense DNA acaricide targeting pre-rRNA of two-spotted spider miteTetranychus urticaeas efficacy-enhancing agent of fungusMetarhizium robertsii
Authors: Gavrilova Daria , Grizanova Ekaterina , Novikov Ilia , Laikova Ekaterina , Zenkova Alexandra , Oberemok Vladimir , Dubovskiy Ivan
Published: October 2024

Two-spotted spider miteTetranychus urticaeKoch (Acari: Tetranychidae) is one of the most dangerous pests in the world and one of the most pesticide-resistant species ever. Complex biological preparations are of great interest for the acaricide market because they do not poison ecosystems and do not bioaccumulate in food products, simultaneously, pests more slowly develop resistance to complex preparations. In this study we applied complex bioformulation composed of 11-mer antisense oligonucleotide (oligonucleotide acaricide or DNA acaricide) Tur-3 and fungusMetarhizium robertsiiforT. urticaecontrol. We discovered that joint contact application of DNA acaricide and fungusM. robertsiisignificantly attenuates reproduction rate of the mite. Our results indicate that DNA acaricide Tur-3 and fungusM. robertsiiact synergistically and lead to a significant 7-times elevated mortality rate and 5-times reduced fecundity of the mite. Oligonucleotide acaricide Tur-3 causes 2,5-fold re-duction of expression of the target pre-rRNA ofT. urticaeand suppresses the activity of key players of detoxifying enzymes of its defense system (phenoloxidase, esterase, glutathione-S-transferase), on average, by 2-3 times. Oligonucleotide acaricide Tur-3 interferes with protein biosynthesis causing decrease in production of defense system enzymes of the pest. Obviously, attenuation of defense system enhances fungal infection or/and fungus produces a variety of enzymes that degrade and destroy the integument structure of the pest, aiding the penetration of oligonucleotide acaricide Tur-3. This research article is the first evidence of successful application of oligonucleotide acaricide together with fungusM. robertsiifor efficientT. urticaecontrol. Combined application of oligonucleotide acaricides based on conservative antisense sequences of rDNA of pests and fungi is a potent and selective approach for eco-friendly plant protection.
Soft biocompatible polymer optical fiber tapers for implantable neural devices
Authors: Meneghetti Marcello , Wang Jiachen , Sui Kunyang , Berg Rune W. , Markos Christos
Published: October 2024

Optical fibers are between the most common implantable devices for delivering light in the nervous system for optogenetics and infrared neural stimulation applications. Tapered optical fibers, in particular, can offer homogeneous light delivery to a large volume and spatially resolved illumination compared to standard flat-cleaved fibers while being minimally invasive. However, the use of tapers for neural applications has up to now been limited to silica optical fibers, whose large Young’s modulus can cause detrimental foreign body response in chronic settings. Here, we present the fabrication and optimization of tapered fiber implants based on polymer optical fibers (POFs). After numerically determining the optimal materials and taper geometry, we fabricated two types of POFs by thermal fiber drawing. The fabrication of the taper was achieved by chemical etching of the fibers, for which several solvents previously reported in literature have been tested. The influence of different parameters on the etching process and on the quality of the obtained tapers was also investigated. The large illumination volume of the produced high-quality taper-based implants was finally testedin vitroin a brain phantom.
A Surface-based deep learning approach for cortical shape analysis
Authors: Im Yanghee , Zhao Yuji , Gutman Boris A. , Thomopoulos Sophia I. , Haddad Elizabeth , Zhu Alyssa H. , Jahanshad Neda , Thompson Paul M. , Ching Christopher R. K.
Published: October 2024

Advances in deep learning hold promise for predicting clinical factors from human brain images. In this study, we applied a spherical harmonics-based convolutional neural network approach (SPHARM-Net) to MRI-derived brain shape metrics to predict age, sex, and Alzheimer’s disease (AD) diagnosis. MRI-derived brain features included vertex-wise cortical curvature, convexity, thickness, and surface area. SPHARM-Net performs convolutions using the spherical harmonic transforms, eliminating the need to explicitly define neighborhood size, and achieving rotational equivariance. Sex classification and age regression were carried out in a large sample of healthy adults (UK Biobank; N=32,979), and AD classification performance was tested in a large, publicly available sample (ADNI; N=1,213). SPHARM-Net showed strong performance for sex classification (accuracy=0.91; balanced accuracy= 0.91; AUC=0.97), and age regression (average absolute error=2.97 years; R-squared=0.77; Pearson’s coefficient=0.9). AD classification also performed well (accuracy=0.86; balanced accuracy=0.83; AUC=0.9). Our experiments demonstrate promising preliminary performance using the SPHARM-Net for two widely studied benchmarking tasks and for AD classification. Future work will include comparisons of shape-based methods and extending these analysis to more challenging tasks such as mood disorder classification.
Exploiting the inherent promiscuity of the acyl transferase of the stambomycin polyketide synthase for the mutasynthesis of analogues
Authors: Su Li , Souaibou Yaouba , Hôtel Laurence , Jacob Christophe , Grün Peter , Shi Yan-Ni , Chateau Alicia , Pinel Sophie , Bode Helge B. , Aigle Bertrand , Weissman Kira J.
Published: October 2024

The polyketide specialized metabolites of bacteria are attractive targets for generating analogues, with the goal of improving their pharmaceutical properties. Here, we aimed to produce C-26 derivatives of the giant anti-cancer stambomycin macrolides using a mutasynthesis approach, as this position has been shown previously to directly impact bioactivity. For this, we leveraged the intrinsically broad specificity of the acyl transferase domain (AT12) of the modular polyketide synthase (PKS), which is responsible for the alkyl branching functionality at this position. Feeding of a panel of synthetic and commercially available dicarboxylic acid ‘mutasynthons’ to an engineered strain ofStreptomyces ambofaciens(Sa) deficient in synthesis of the native α-carboxyacyl-CoA extender units, resulted in six new series of stambomycin derivatives as judged by LC-HRMS and NMR. Notably, the highest product yields were observed for substrates which were only poorly accepted when AT12was transplanted into a different PKS module, suggesting a critical role for domain context in the overall functioning of PKS proteins. We also demonstrate the superiority of this mutasynthesis approach − both in terms of absolute titers and yields relative to the parental compounds − in comparison to the alternative precursor-directed strategy in which monoacid building blocks are supplied to the wild type strain. We further identify a malonyl-CoA synthetase, MatB_Sa, with specificity distinct from previously identified promiscuous enzymes, making it a useful addition to a mutasynthesis toolbox for generating atypical, CoA activated extender units. Finally, we show that two of the obtained (deoxy)-butyl-stambomycins exhibit antibacterial and antiproliferative activities similar to the parental stambomycins, while an unexpected butyl-demethyl congener is less potent. Overall, this works confirms the interest of biosynthetic pathways which combine a dedicated route to extender unit synthesis and a broad specificity AT domain for producing bioactive derivatives of fully-elaborated complex polyketides.
Targeted therapy of oncomicrobeF. nucleatumwith bioengineered probiotic expressing guided antimicrobial peptide (gAMP)
Authors: Choudhury Ankan , Scano Colin , Barton Allison , Kearney Christopher M. , Greathouse K. Leigh
Published: October 2024

Colorectal cancer (CRC) is a leading cause of cancer-related mortality, withFusobacterium nucleatum(F. nucleatum) identified as a key contributor to its progression. This study explores a novel targeted therapy using bioengineered probiotics expressing guided antimicrobial peptides (gAMPs) to selectively inhibitF. nucleatum. We engineeredLactococcus lactisMG1363 to express gAMPs derived from Ovispirin and Cathelin-related peptide SCF, linked to a Statherin-derived guide peptide (YQPVPE) that binds specifically to theF. nucleatummembrane porin FomA.

Our results demonstrate that the Statherin-derived guide peptide enhances the binding affinity toF. nucleatum, significantly increasing the preferential attachment compared to control peptides. In vitro assays revealed that both unguided and guided AMPs effectively inhibited biofilm formation inF. nucleatum, with gAMPs showing reduced toxicity against non-target bacteria (Bacteroides fragilisandEscherichia coli). The gAMPs were also more effective in modulating growth kinetics, exhibiting selective toxicity towardsF. nucleatumat lower concentrations.

Co-culture experiments in a simulated human gut microbiome demonstrated that the gAMP probiotic maintained microbial diversity while effectively reducingF. nucleatumabundance. Quantitative PCR and 16S rRNA sequencing confirmed that gAMP treatment preserved the richness of the microbiota, contrasting with significant dysbiosis observed in control samples.

These findings support the potential of engineered probiotics as a targeted therapeutic approach to combatF. nucleatum-associated CRC. By leveraging the specificity of Statherin-derived peptides, this strategy not only addresses the pathogenicity ofF. nucleatumbut also mitigates the adverse effects of traditional antimicrobial therapies on beneficial gut microbiota. Future studies will explore the clinical applicability of this approach in CRC management and its impact on overall gut health.
Scientific reasoning driven by influential data: resuscitatedfstat!
Authors: Spiess Andrej-Nikolai , Rödiger Stefan , Schaks Matthias , Burdukiewicz Michał , Tellinghuisen Joel
Published: October 2024

In biomedical literature, one of the most widely employed statistical procedures to analyze and visualize the association between two variables is linear regression. Data points that exert influence on the fit and its parameters are routinely, but not as often as required, identified by established influence measures and their corresponding cut-off values. In this work, we are specifically concerned with the presence of influential data points that directly impact hypothesis testing of linear regressions, which none of the established measures describe. Interestingly, the highly overlooked influence measuredfstatand its derived leave-one-outp-value exists exactly for this purpose, unmentioned in the majority of statistical text books as well as absent from all available statistical software packages. Its application for identifying these data points seems pivotal, as scientific reasoning in publications is almost exclusively based on thep-value of the fit, commonly adhering to the α = 0.05 threshold to state significance or not. With this metric, we found for 29 of 100 digitizable papers published inScience, NatureandPNASin 2016, a time when the “reproducibility crisis” was a growing concern, that stated significances (or their absence) are based on the presence of a single influential data point.
Erratum: Optimal Zeno Dragging for Quantum Control: A Shortcut to Zeno with Action-Based Scheduling Optimization [PRX Quantum 5, 020366 (2024)]
Authors: Lewalle Philippe , Zhang Yipei , Whaley K. Birgitta
Published: October 2024

We correct a misleading typo present in two equations of our paper [1]. While the final results in these two expressions and subsequent examples were correct, an important term was missing from a pair of intermediate expressions.

Published by the American Physical Society
2024
Crystal structure of nickel orthovanadate (Ni3V2O8) at 299 (3) K and 1323 (8) K: an X-ray diffraction study
Authors: Aziz Fiza , Paszkowicz Wojciech , Minikayev Roman , Martin Christine , Kozlowski Miroslaw , Teisseyre Henryk
Published: October 2024

Nickel orthovanadate is a promising material with potential applications in energy storage and photocatalytic devices. The crystal structure of Ni3V2O8 at 299 (3) K and 1323 (8) K was studied using X-ray powder diffraction. The sample was a single-phase orthorhombic kagome-staircase-Ni3(VO4)2-type structure (space group Cmca) at both temperatures. The phase purity and morphology was studied using energy-dispersive X-ray spectroscopy and scanning electron microscopy. The refined unit-cell parameters at 299 (3) K are a = 5.93384 (4) Å, b = 11.38318 (7) Å and c = 8.23818 (5) Å, and at 1323 (8) K are a = 6.02077 (7) Å, b = 11.48838 (7) Å and c = 8.32611 (9) Å. The obtained results indicate thermal expansion anisotropy, with a largest expansivity along a. Variations in Ni—O and V—O bonds with temperature are observed. The variation in the Ni—O bond is about one order higher in magnitude than that of the V—O bond, signifying the high rigidity of V—O bonds. The unit-cell size variations with rising effective ionic volume of the divalent A ion in the A
3
B
2O8 family [A = Ni, Mg, Zn, Co, Mn (experimental data) and also A = Cu, Cd (theoretical data), B = V or As] are analyzed. Based on experimental and theoretical data, trends within the family are observed and the unit-cell size for reported solid solution of nickel (87%) and copper (13%) mixture in (Ni1–x
Cu
x
)3V2O8 are predicted. Predictions are also provided for some hypothetical A
3
B
2O8 ternary compound and solid solutions.
Spin reorientation and the interplay of magnetic sublattices in Er2CuMnMn4O12
Authors: Attah-Baah John M. , Khalyavin Dmitry D. , Manuel Pascal , Ferreira Nilson S. , Belik Alexei A. , Johnson Roger D.
Published: October 2024

Through a combination of magnetic susceptibility, specific heat, and neutron powder diffraction measurements we have revealed a sequence of four magnetic phase transitions in the columnar quadruple perovskite Er2CuMnMn4O12. A key feature of the quadruple perovskite structural framework is the complex interplay of multiple magnetic sublattices via frustrated exchange topologies and competing magnetic anisotropies. It is shown that in Er2CuMnMn4O12, this phenomenology gives rise to multiple spin-reorientation transitions driven by the competition of easy-axis single ion anisotropy and the Dzyaloshinskii–Moriya interaction; both within the manganese B-site sublattice. At low temperature, one Er sublattice orders due to a finite f-d exchange field aligned parallel to its Ising axis, while the other Er sublattice remains non-magnetic until a final, symmetry-breaking phase transition into the ground state. This non-trivial low-temperature interplay of transition metal and rare-earth sublattices, as well as an observed k = (0, 0, ½) periodicity in both manganese spin canting and Er ordering, raises future challenges to develop a complete understanding of the R
2CuMnMn4O12 family.
Entrepreneurial alertness and new firm performance: a moderated mediation model
Authors: Montiel-Campos Hector
Published: October 2024

Purpose

Supported by the literature on dynamic capabilities, this study aims to propose a moderated mediation model to examine how entrepreneurial alertness advances new firm performance by identifying strategic flexibility as a pivotal mediator and absorptive capacity as a crucial contingency.

Design/methodology/approach

This paper collects data from 137 new firms regarding activities that were considered essential during the COVID-19 contingency in Mexico. The hypotheses are tested using hierarchical multiple regression analysis, complemented with the bootstrapping approach to confirm the indirect and conditional effects of entrepreneurial alertness on firm performance through strategic flexibility.

Findings

The results yielded general support for the study hypotheses, suggesting that entrepreneurs’ alertness facilitates the firms’ ability to respond to changes in their context, namely, strategic flexibility; strategic flexibility enables firms make useful changes, leading to better performance; entrepreneurial alertness indirectly affects new firm performance through strategic flexibility; absorptive capacity has a positive moderating impact on the entrepreneurial alertness-strategic flexibility relationship; and the positive influence of entrepreneurial alertness on strategic flexibility and ultimately new firm performance was increased in high rather than in low absorptive capacity.

Practical implications

This study highlights that entrepreneurs’ cognitive mechanisms shape the behaviour of their firms through strategic decisions. This paper studies the influence of entrepreneurs’ alertness on strategic flexibility, examines the interplay between entrepreneurial alertness and environmental conditions via absorptive capacity and proposes a moderated mediation model to understand the effect of entrepreneurs’ alertness on strategic flexibility and new firm performance.

Originality/value

The study investigates the influence of assertive message framing and individual value orientations on the reactance process in the context of environmentally friendly mobility. It finds individual value orientations to be a significant factor in the reactance process, further extending the psychological reactance theory. Moreover, it revalidates reactance as a construct consisting of anger and negative cognition.
Does telemedicine hold the key for reproductive health care? A quantitative examination of women's intentions toward use and accurate information disclosure
Authors: Fox Grace , Lynn Theo , van der Werff Lisa , Kennedy Jennifer
Published: October 2024

Objective

To investigate women's perceptions of telemedicine for reproductive health care services, focusing on how perceived benefits and privacy risks influence their intentions to adopt telemedicine and their willingness to disclose personal health information.

Study Setting and Design

A cross‐sectional survey was conducted. The study applied the privacy calculus theory to the context of telemedicine for reproductive health, using adapted, validated variables to develop the survey. Outcome variables included intentions to adopt telemedicine and willingness to disclose accurate personal health information.

Data Sources and Analytic Sample

Data were collected in May and June 2023 using Qualtrics online panel services, targeting women across the United States who had not used telemedicine for reproductive health. The sample comprised 847 women aged 18 and older. Structural equation modeling was employed using AMOS v28.0 to test the hypothesized relationships between perceived benefits, perceived risks, and adoption intentions. The analysis controlled for age, household income, political affiliation, religious views, and prior births.

Principal Findings

Perceived benefits were positively related to intention to adopt telemedicine for reproductive care (β: 0.600, p < 0.001), and willingness to disclose accurate personal health information (β: 0.453, p < 0.001). Unexpectedly, perceived privacy risks were positively related to adoption intentions (β: 0.128, p < 0.001), but negatively related to willingness to disclose (β: −0.282, p < 0.001). Intentions to adopt were positively associated with willingness to disclose (β: 0.089, p < 0.05). Lastly, older women and women located in states with abortion restrictions expressed lower intentions to adopt. The model explained 40.2% of variance in intention to adopt and 38.3% of variance in willingness to disclose.

Conclusions

The study demonstrates the importance of perceived benefits and privacy risks in driving telemedicine adoption and disclosure intentions among women in the reproductive health context. These findings suggest the need for targeted strategies to address privacy concerns and support telemedicine adoption, particularly in restrictive regulatory environments.
The synergy of renewable energy consumption, green technology, and environmental quality: Designing sustainable development goals policies
Authors: Caglar Abdullah Emre , Daştan Muhammet , Ahmed Zahoor , Mert Mehmet , Avci Salih Bortecine
Published: October 2024

Green technology (GT) and the utilization of renewable energy (RE) are widely acknowledged as a catalyst for energy efficiency, economic growth, and a tool for combating environmental degradation. Although various studies have examined the ecological repercussions of these two improvements, they have primarily used traditional pollution indicators (namely, carbon emissions and ecological footprint) and ignored nations with the highest cleaner energy adoption. To bridge this gap, the present research seeks to analyze the relationship between GT, RE consumption, economic growth, trade, and load capacity factor in the top‐10 renewable economies. In addition to environmental pollution indicators, the study utilizes the load capacity factor as a novel proxy for environmental quality and investigates the load capacity curve hypothesis using the Cross‐sectional‐autoregressive distributed lag model from 1990 to 2021. According to the empirical findings, all explanatory variables have a significant long‐term effect on the load capacity. More precisely, GT and RE consumption contribute to the sustainability of the ecosystem, while trade increases the ecological deficit. Furthermore, the findings do not support the validity of the load capacity curve hypothesis, implying that the environmental restorative benefits of economic well‐being may not manifest in the latter stages of economic growth. Given these findings, policymakers in the top‐10 renewable economies should seize the environmental prospects offered by GT and RE and update trade and growth policies in a way that promotes biocapacity while simultaneously reducing the ecological footprint to reach the long‐term sustainable development goals (SDGs), particularly SDGs 7 and 13.