bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anticancer drug doxorubicin spontaneously reacts with GTP and dGTP
Authors: Mejia German , Su Linjia , Pandey Popular , Dit Fouque Kevin Jeanne , McGoron Anthony , Fernandez-Lima Francisco , He Jin , Mebel Alex , Leng Fenfei 
Published: October 2022

AbstractHere we reported a spontaneous reaction between anticancer drug doxorubicin and GTP or dGTP. Incubation of doxorubicin with GTP or dGTP at 37 °C or above yields a covalent product: the doxorubicin-GTP or -dGTP conjugate where a covalent bond is formed between the C14 position of doxorubicin and the 2-amino group of guanine. Density functional theory calculations show the feasibility of this spontaneous reaction. Fluorescence imaging studies demonstrate that the doxorubicin-GTP and -dGTP conjugates cannot enter nuclei although they rapidly accumulate in human SK-OV-3 and NCI/ADR-RES cells. Consequently, the doxorubicin-GTP and -dGTP conjugates are less cytotoxic than doxorubicin. We also demonstrate that doxorubicin binds to ATP, GTP, and other nucleotides with a dissociation constant (Kd) in the sub-millimolar range. Since human cells contain millimolar levels of ATP and GTP, these results suggest that doxorubicin may target ATP and GTP, energy molecules that support essential processes in living organisms.
Loss of GABA co-transmission from cholinergic neurons impairs behaviors related to hippocampal, striatal, and medial prefrontal cortex functions
Authors: Goral R. Oliver , Harper Kathryn M. , Bernstein Briana J. , Fry Sydney A. , Lamb Patricia W. , Moy Sheryl S. , Cushman Jesse D. , Yakel Jerrel L. 
Published: October 2022

AbstractAltered signaling or function of acetylcholine (ACh) has been reported in various neurological diseases, including Alzheimer’s disease, Tourette syndrome, epilepsy among others. Many neurons that release ACh also co-transmit the neurotransmitter gamma-aminobutyrate (GABA) at synapses in the hippocampus, striatum, and medial prefrontal cortex (mPFC). Although ACh transmission is crucial for higher brain functions such as learning and memory, the role of co-transmitted GABA from ACh neurons in brain function remains unknown. Thus, the overarching goal of this study was to investigate how a systemic loss of GABA co-transmission from ACh neurons affected the behavioral performance of mice. To do this, we used a conditional knock-out mouse of the vesicular GABA transporter (vGAT) crossed with the ChAT-Cre driver line to selectively ablate GABA co-transmission at ACh synapses. In a comprehensive series of standardized behavioral assays, we compared Cre-negative control mice with Cre-positive vGAT knock-out mice of both sexes. Loss of GABA co-transmission from ACh neurons did not disrupt the animal’s sociability, motor skills or sensation. However, in the absence of GABA co-transmission, we found significant alterations in social, spatial and fear memory as well as a reduced reliance on striatum-dependent response strategies in a T-maze. In addition, male CKO mice showed increased locomotion. Taken together, the loss of GABA co-transmission leads to deficits in higher brain functions and behaviors. Therefore, we propose that ACh/GABA co-transmission modulates neural circuitry involved in the affected behaviors.
Scratch-AID: A Deep-learning Based System for Automatic Detection of Mouse Scratching Behavior with High Accuracy
Authors: Yu Huasheng , Xiong Jingwei , Ye Adam Yongxin , Cranfill Suna Li , Cannonier Tariq , Gautam Mayank , Zhang Marina , Bilal Rayan , Park Jong-Eun , Xue Yuji , Polam Vidhur , Vujovic Zora , Dai Daniel , Ong William , Ip Jasper , Hsieh Amanda , Mimouni Nour , Lozada Alejandra , Sosale Medhini , Ahn Alex , Ma Minghong , Ding Long , Arsuaga Javier , Luo Wenqin 
Published: October 2022

AbstractMice are the most commonly used model animals for itch research and for development of antiitch drugs. Most labs manually quantify mouse scratching behavior to assess itch intensity. This process is labor-intensive and limits large-scale genetic or drug screenings. In this study, we developed a new system, Scratch-AID (Automatic Itch Detection), which could automatically identify and quantify mouse scratching behavior with high accuracy. Our system included a custom-designed videotaping box to ensure high-quality and replicable mouse behavior recording and a convolutional recurrent neural network (CRNN) trained with frame-labeled mouse scratching behavior videos, induced by nape injection of chloroquine (CQ). The best trained network achieved 97.6% recall and 96.9% precision on previously unseen test videos. Remarkably, Scratch-AID could reliably identify scratching behavior in other major mouse itch models, including the acute cheek model, the histaminergic model, and a chronic itch model. Moreover, our system detected significant differences in scratching behavior between control and mice treated with an anti-itch drug. Taken together, we have established a novel deep learning-based system that is ready to replace manual quantification for mouse scratching behavior in different itch models and for drug screening.
Activity of tonically active neurons in the primate striatum reflects interaction between time processing and reward prediction
Authors: Martel A.-C , Apicella P. 
Published: October 2022

AbstractThe striatum and its dopaminergic input participate in temporal processing and numerous studies provide evidence that interactions between dopamine and acetylcholine are critical for striatal functioning. However, the role of local cholinergic innervation of the striatum in behaviors requiring precise timing has not been specifically investigated. Here, we recorded from presumed striatal cholinergic interneurons, identified as tonically active neurons (TANs), in two male rhesus monkeys performing self-initiated movements after specified learned time intervals have elapsed since a visual cue. We found that 38% of all recorded TANs responded to the cue with a pause in firing and the strength of these responses could be modulated according to the duration of the interval being timed and the accuracy of time estimates. By examining the TAN response to the reward itself and by recording from TANs during a Pavlovian procedure in which no action was required, we found evidence that TAN activity modulation may potentially reflect differences in the animal’s prediction of reward. Thus, besides their well-known role in predicting and detecting rewarding events, TANs may generate signals related to the processing of time. Our findings suggest a role of the local cholinergic circuitry in the representation of time within the striatum.
Charting the development ofDrosophilaleg sensory organs at single-cell resolution
Authors: Hopkins Ben R. , Barmina Olga , Kopp Artyom 
Published: October 2022

AbstractTo respond to the world around them, animals rely on the input of a network of sensory organs distributed throughout the body. Distinct classes of sensory organ are specialized for the detection of specific stimuli such as strain, pressure, or taste. The features that underlie this specialization relate both to the neurons that innervate sensory organs and the accessory cells that comprise them. This diversity of cell types, both within and between sensory organs, raises two fundamental questions: what makes these cell types distinct from one another, and how is this diversity generated during development? To address these questions, we performed single-cell RNA sequencing on a developing tissue that displays a wide variety of functionally and structurally distinct sensory organs: the first tarsal segment of the pupal maleDrosophila melanogasterforeleg. We characterize the cellular landscape in which the sensory organs reside, identify a novel cell type that contributes to the construction of the neural lamella, and characterize the transcriptomic differences among support cells within and between sensory organs. We identify the genes that distinguish between mechanosensory and chemosensory neurons, resolve a combinatorial transcription factor code that defines four distinct classes of gustatory neuron and several types of mechanosensory neuron, and match the expression of sensory receptors to specific neuron classes. Collectively, our work identifies core genetic features of a variety of sensory organs and provides a rich, annotated resource for studying their development and function.
Structural basis of epitope selectivity and potent protection from malaria by PfCSP antibody L9
Authors: Martin Gregory M. , Fernández Quintero Monica L. , Lee Wen-Hsin , Pholcharee Tossapol , Eshun-Wilson Lisa , Liedl Klaus R. , Pancera Marie , Seder Robert A. , Wilson Ian A. , Ward Andrew B. 
Published: October 2022

AbstractA primary objective in malaria vaccine design is the generation of high-quality antibody responses against the circumsporozoite protein of the malaria parasite, Plasmodium falciparum (PfCSP). To enable rational antigen design, we solved a cryo-EM structure of the highly potent anti-PfCSP antibody L9 in complex with recombinant PfCSP. We found that L9 Fab binds multivalently to the CSP minor (NPNV) repeats, which is stabilized by a novel set of affinity-matured homotypic, antibody-antibody contacts. Molecular dynamics simulations revealed a critical role of the L9 light chain in integrity of the homotypic interface, which likely impacts CSP affinity and protective efficacy. These findings reveal the molecular mechanism of the unique NPNV selectivity of L9 and emphasize the importance of anti-homotypic affinity maturation in protective immunity against P. falciparum.One sentence summaryThe L9 light chain is crucial for potency by conferring multivalent, high affinity binding to the NPNV minor repeats of PfCSP.
Novel Context-Specific Genome-Scale Modelling Explores the Potential of Chlamydomonas reinhardtii for Synthetic Biology Applications
Authors: Yao Herbert , Dahal Sanjeev , Yang Laurence 
Published: October 2022

AbstractGene expression data of cell cultures is commonly measured in biological and medical studies to understand cellular decision-making in various conditions. Metabolism, affected but not solely determined by the expression, is much more difficult to measure experimentally. Thus, finding a reliable method to predict cell metabolism for given expression data will greatly benefit model-aided metabolic engineering. We have developed such a pipeline that can explore cellular fluxomics from expression data, using only a high-quality genome-scale metabolic model. This is done through two main steps: first, construct a protein-constrained metabolic model by integrating protein and enzyme information into the metabolic model. Secondly, overlay the expression data onto the modified model using a new two-step non-convex and convex optimization formulation, resulting in context-specific models with optionally calibrated rate constants. The resulting model computes proteomes and intracellular flux states that are consistent with the measured transcriptomes. Therefore, it provides detailed cellular insights that are difficult to glean individually from the omic data or metabolic models alone. As a case study, we apply the pipeline to interpret triacylglycerol (TAG) overproduction by Chlamydomonas reinhardtii, using time-course RNA-Seq data. The pipeline allows us to compute C. reinhardtii metabolism under nitrogen deprivation and metabolic shifts after an acetate boost. We also suggest a list of possible ‘bottlenecking’ proteins that need to be overexpressed to increase the TAG accumulation rate, as well as discussing other TAG-overproduction strategies.
Profiling neurons surrounding subcellular-scale carbon fiber electrode tracts enables modeling recorded signals
Authors: Letner Joseph G. , Patel Paras R. , Hsieh Jung-Chien , Flores Israel M. Smith , Valle Elena della , Walker Logan A. , Weiland James D. , Chestek Cynthia A. , Cai Dawen 
Published: October 2022

SummaryCharacterizing the relationship between neuron spiking and the signals electrodes record is vital to defining the neural circuits driving brain function and informing computational modeling. However, electrode biocompatibility and precisely localizing neurons around the electrodes are critical to defining this relationship. Here, we show the ability to localize post-explant recording tips of subcellular-scale carbon fiber electrodes and surrounding neurons. Immunostaining of astrocyte, microglia, and neuron markers confirmed improved tissue health. While neurons near implants were stretched, their number and distribution were similar to control, suggesting that these minimally invasive electrodes demonstrate the potential to sample naturalistic neural populations. This motivated prediction of the spikes produced by neurons nearest to the electrodes using a model fit with recorded electrophysiology. These simulations show the first direct evidence that neuron placement in the immediate vicinity of the recording site influences how many spike clusters can be reliably identified by spike sorting.
Multi-omic modeling of antidepressant response implicates dynamic immune and inflammatory changes in individuals who respond to treatment
Authors: Fuh Shih-Chieh , Fiori Laura M. , Turecki Gustavo , Nagy Corina , Li Yue 
Published: October 2022

AbstractMajor depressive disorder (MDD) is a leading cause of disability worldwide, and is commonly treated with antidepressant drugs (AD). Although effective, many patients fail to respond to AD treatment, and accordingly identifying factors that can predict AD response would greatly improve treatment outcomes. In this study, we developed a machine learning tool to integrate multi-omic datasets (gene expression, DNA methylation, and genotyping) to identify biomarker profiles associated with AD response in a cohort of individuals with MDD. To address this rich multi-omic dataset with high dimensional features, we developed integrative Geneset-Embedded non-negative Matrix factorization (iGEM), a non-negative matrix factorization (NMF) based model, supplemented with auxiliary information regarding genesets and gene-methylation relationships. Using our model, we identified a number of meta-phenotypes which were related to AD response. By integrating geneset information into the model, we were able to relate these meta-phenotypes to biological processes, including immune and inflammatory functions. This represents both biomarkers to predict response, as well as potential new treatment targets. Our method is applicable to other diseases with multi-omic data, and the software is open source and available on Github (https://github.com/li-lab-mcgill/iGEM).
Inflammation of the retinal pigment epithelium drives early-onset photoreceptor degeneration inMertk-associated retinitis pigmentosa
Authors: Mercau Maria E. , Akalu Yemsratch T. , Mazzoni Francesca , Gyimesi Gavin , Alberto Emily , Kong Yong , Hafler Brian P. , Finnemann Silvia C. , Rothlin Carla V. , Ghosh Sourav 
Published: October 2022

AbstractSevere, early-onset photoreceptor (PR) degeneration associated withMERTKmutations is thought to result from failed phagocytosis by retinal pigment epithelium (RPE). Notwithstanding, the severity and onset of PR degeneration in mouse models ofMertkablation is determined by the hypomorphic expression or the loss of theMertkparalogTyro3. Here we find that loss ofMertkand reduced expression/loss ofTyro3led to RPE inflammation even before eye-opening. Incipient RPE inflammation cascaded to involve microglia activation and PR degeneration with monocyte infiltration. Inhibition of RPE inflammation with the JAK1/2 inhibitor ruxolitinib mitigated PR degeneration inMertk-/-mice. Neither inflammation nor severe, early-onset PR degeneration were observed in mice with defective phagocytosis alone. Thus, inflammation drives severe, early-onset PR degeneration-associated withMertkloss of function.
Screening and diagnosing dementia in people with Down’s syndrome: implications of using the DLD questionnaire
Authors: Perera Bhathika , Kamieniarz Lukasz , Iftikhar Mashal , Solomou Solomis 
Published: October 2022

PurposeThe Dementia Questionnaire for People with Learning Disabilities (DLD) is one of the main screening and monitoring tools for dementia in people with Down’s syndrome (DS). As part of a quality improvement project to improve the care for people with DS and dementia in an intellectual disability service, the authors studied the screening and monitoring process by retrospectively investigating the use of DLD and exploring clinicians’ experience of using it.Design/methodology/approachDLDs completed in the service was retrospectively assessed. Changes in DLD scores were matched against people who received a clinical diagnosis of dementia. Data were analysed to estimate sensitivity, specificity and predictive values of DLD. A questionnaire was used to assess clinicians’ experience.FindingsData for 20 service users was collected. DLD cognitive scores showed 80% sensitivity and 60% specificity for the diagnosis of dementia, with a positive predictive value of 40% and negative predictive value of 90%. Staff found DLD to be easy to perform but time consuming. This led to the preparation of a decision tool for appropriateness of performing a DLD.Originality/valueThe results show that a negative DLD helps to exclude dementia where there is concern over cognitive decline, but a positive result is not specific enough to suggest the possibility of dementia. This shows that DLD may have limitations if used as a screening tool alone but could be used for the monitoring of the disease trajectory of those with a confirmed diagnosis as well as to establish a baseline DLD when a person is screened for dementia first.
Young people’s preferences in public spaces
Authors: Khalifa Sara Ibrahim , Shafik Zeinab , Shehayeb Dina 
Published: October 2022

PurposeFew public places are designed with due consideration to the needs and preferences of teens. Teens in public spaces are often viewed with apprehension from other user groups. Teens hanging out in public spaces are always observed with caution and are sometimes associated with negative behaviour by other community members. In designing public spaces that are suitable for the teens and not alienating them to other members of the community, it is necessary to understand how teens perceive their environment and what they expect from it. The psychological, social and emotional development determines the teens’ preferences regarding public spaces. This research attempts to understand how teens perceive and value those places and the factors that influence teens’ preferences in public spaces. This study aims to deduce some factors that influence teens’ preferences and behaviour from an environmental psychology perspective and then test these factors on a sample of teenagers in an Egyptian setting.Design/methodology/approachAn empirical study was conducted with teens in two districts in Cairo, Egypt: “Dokki” and “Sheikh Zayed,” to understand how teens perceive their neighbourhoods, identify preferred places and discern factors that influence their preferences. A sample of 67 teens, aged between 13 and 19 years old, in which 31 were males, and 36 were females, completed a survey that allowed teens to identify and rate their experiences. This occurred using a map-based mobile application to foster more active engagement by participants, in which they identified their favourite places, the behaviour associated with these places, what teens do there – when, and with whom, as well as their rating of the place.FindingsThe most important conclusion drawn from this study was that teens’ preferences are linked to their cognitive, emotional and social development. They influence and are associated with essential aspects such as the sense of freedom, sense of safety, self-identity, enjoyment, thrill-seeking and peer relationships. Therefore, it is important to adopt a new perspective to the design of public spaces to create teen-friendly places.Originality/valueAdopt a new perspective to public space design to create teen-friendly places by adopting an environmental psychology lens to shed light on the social and psychological dimensions of the built environment.
Towards circular economy practices in food waste management: a retrospective overview and a research agenda
Authors: Alonso-Muñoz Sara , García-Muiña Fernando E. , Medina-Salgado María-Sonia , González-Sánchez Rocío 
Published: October 2022

PurposeThis study aims to offer a research overview of circular food waste management, covering key themes and trends. It analyses state-of-the-art research in this field and proposes an agenda to guide future research.Design/methodology/approachThis study outlines bibliometric analysis from a sample of 349 articles with VOSviewer and SciMat software to identify research trend topics.FindingsThe findings reveal a substantial amount of interest in this field. The main research topics relate to the recovery processes and valorisation of food waste and its conversion into renewable and cleaner materials or energy sources, towards circularity. However, these processes require consideration of social aspects that facilitate their implementation, which are currently under-researched.Practical implicationsCompanies can target their circular food waste management by considering three key aspects. Firstly, the establishment of closer and more sustainable relationships with various stakeholders; Secondly, a regulatory framework and the support of institutions are both required for the correct implementation of circularity. Finally, what is not measured does not exist. It is therefore necessary to establish indicators to measure both the level of development of circularity in waste management and the fulfilment of the established objective.Originality/valueThis bibliometric analysis looks at the application of circularity principles in food waste management from a holistic perspective, considering different areas of knowledge.
Reid & Taylor: the ignominious decline of an iconic brand
Authors: John Kishore Thomas 
Published: October 2022

Learning outcomes
The learning outcomes of this case are in understanding core concepts of brand management and brand dilution. Assessment of macro-economic risks and proper positioning strategies are the key take-away from this case. The case gives an understanding of how brands are built and positioned, and the pitfalls of poor brand planning and assessment that could lead to brand dilution. The case is useful for highlighting the importance of brand management and the challenges of re-positioning. The discussions would shed light on why it is important to plan and manage spending on marketing for brand building activities, and why brands would suffer when spending is reduced. This case is a teaching case and not a research case. It will help participants assimilate available information in combination with existing academic theories and publications to help develop an accurate assessment and prognosis of the events leading until the point of slicing the case.

Case overview/synopsis
Reid & Taylor in 2015 had been reduced to a discounter brand offering extended end-of-season sales when most other competitors have ended their promotions. In the 17 years since its big-budget launch in the Indian market in one of the most memorable brand introductions, Reid & Taylor changed its ambassador twice and repositioned itself thrice. The case would allow participants to delve deeper into aspects of marketing spending, brand management, positioning and advertising effectiveness. The case brings to the fore discussions on marketing, specifically on branding, positioning and its related advertising in the textile sector for a brand that has not been studied in academic literature until the present time. The discussion allows for novelty, involving both forward- and backward-looking assessments and evaluations to help participants better imbibe learnings in brand management and positioning.

Complexity academic level
The case is suitable for a graduate-level (Master’s level) course in marketing and brand management. This case is suitable for elective courses that discuss positioning and brands.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS 8: Marketing