bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the structural basis for differential binding of lapachol with PfHSP70s
Authors: Singh Bikramjit , Kaur Satinder , Sandhu Komalpreet Kaur , Nainani Chanchal , Upadhyay Vipul , Hora Rachna , Mishra Prakash Chandra 
Published: July 2023

AbstractThe 70 kDa heat shock proteins fromPlasmodium falciparum(PfHSP70) are an important family of proteins that may be exploited for antimalarial design. Plant derived inhibitor ‘lapachol’ is reported to efficiently inhibit the exported PfHSP70-x while having poor activity against the parasite PfHSP70-1. In the present study, we have usedin silicotools including molecular docking to understand the molecular basis for the above differences in lapachol inhibition activity against PfHSP70s. We found a significant gap in the binding energies and hence affinity of PfHSP70-1 and PfHSP70-x for lapachol with the latter having a better binding propensity. Our data highlight notable differences in the type of interactions between the two complexes. Detailed molecular analysis of the complexes has helped us to predict specific amino acid residues from both these PfHSP70 homologs that may be involved in lapachol binding. The above information may be utilized for design of PfHSP70 inhibitors with antimalarial potential.
Hundreds of independent midsize deletions mediate DNA loss in wild relatives of Red Jungle Fowl
Authors: Sharma Ashutosh , Shinde Sagar Sharad , Vijay Nagarjun 
Published: July 2023

AbstractSmall and midsize deletions and insertions (InDels) are major events that play a crucial role in the evolution of genome size and contribute to the genetic and phenotypic diversity of species. In recent years, considerable attention has been given to studying small indels associated with various developmental, growth, and production traits in domestic chicken breeds. Additionally, small and midsize indels have been studied between chicken and phylogenetically more distant species such as duck, turkey, rock pigeon, and other passerine birds. However, the investigation of small and midsize deletions in the wild relatives of chickens has been relatively overlooked until now. To address this gap, our study aimed to identify the presence and distribution of midsize deletions (> 1 Kb) in the wild relatives of chickens. We conducted a comparative genomic analysis using high-quality genomic data from four species belonging to theGallusgenus. Our analysis revealed the existence of more than 125 midsize deletions in the three other species compared toGallus gallus(red junglefowl). These midsize deletions were found to be distributed in intergenic regions and within introns of various protein-coding genes but not in the exonic regions of protein-coding genes. Furthermore, we observed a trend between the number of midsize deletions and the phylogenetic distance in the phylogeny of theGallusgenus. The most ancestral species,Gallus varius(green junglefowl), exhibited the highest deletions, followed byGallus lafayettii(Ceylon junglefowl) andGallus sonneratii(grey junglefowl). Some protein-coding genes harboring deletions in their introns and upstream regions were associated with body development, production, growth traits, abdominal fat deposition, behavioral patterns such as stress, fear, anxiety, plumage color, and adaptation to extreme climatic conditions. Our study finds that the midsize deletions identified in wild relatives of red junglefowl contribute less than 1% of DNA loss with a rate of 8-44 Kb/My during the evolution of theGallusgenus.
Impact of Microscopic Quantum Mechanisms on Macroscopic Epigenetic Regulation through Histone Deacetylation
Authors: Yasuda Takeshi , Ogi Tomoo , Nakajima Nakako , Yanaka Tomoko , Tanaka Izumi , Tajima Katsushi 
Published: July 2023

AbstractThe question of whether physical phenomena at a quantum level significantly impact aspects of macroscopic life has long remained unanswered. Histone modification by acetylation regulates the transcriptional activity of genes, and thereby broadly impacts cellular metabolism. In chemical reactions, the quantum tunneling effect is a phenomenon in which a small quantum particle of the reactant can pass through the potential energy barrier, even if it does not have sufficient energy to overcome the barrier. Here, we demonstrated that quantum effects are involved in the enzymatic reaction of histone deacetylation, by monitoring kinetic isotope effects due to hydrogen isotopes of water molecules and their temperature dependence as indicators. Due to the kinetic isotope effects associated with the quantum effects, the reaction rate balance between histone acetylation and deacetylation in cells was altered with heavy water, which changed epigenetic transcription regulation in the cells. Thus, microscopic quantum mechanisms exist in histone deacetylation, thereby broadly impacting macroscopic life phenomena through epigenetic regulation.TeaserQuantum effects in enzymatic reaction of histone deacetylation latently influence life phenomena through epigenetic regulation.
Effects of Alternative Splicing-Specific Knockdown of Tjp1 α+ by Rbm47 on Tight Junctions Assembly during Blastocyst Development
Authors: Jeong Jiyeon , Choi Inchul 
Published: July 2023

AbstractTjp1 α+ is considered a crucial protein involved in the stepwise assembly of tight junctions (TJs) between compaction and blastocoel cavitation in early development. In this study, we investigated the specific role of Tjp1 α+ in TJ formation by employing an alternative splicing-specific knockdown of the Tjp1 α+ exon. To deplete Tjp1 α+ expression, we used siRNA targeting RNA-binding protein 47 (Rbm47), which induces the inclusion of the α+ exon in Tjp1 mRNA. The knockdown resulted in approximately 85% reduction in Rbm47 mRNA levels and 75% reduction in Tjp1 α+ mRNA levels in blastocysts. Surprisingly, despite this knockdown, blastocyst development and TJ permeability of trophectoderm were unaffected. Additionally, we observed an interaction between Tjp1 α- and Ocln in Rbm47 knockdown blastocysts, suggesting a compensatory role of Tjp1 α-. Overall, our findings indicate that Tjp1 α+ is not essential for the stepwise assembly of TJs and the completion of TJ biogenesis during blastocyst development in mice although a minimal amount of remaining Tjp1 α+ is sufficient for TJs assembly.Summary statementSelective loss of Tjp1 α+ mediated by Rbm47 knockdown did affect mouse blastocyst development, suggesting that Tjp1 α+ may not be crucial for stepwise TJs assembly during blastocyst development
A multistagePlasmodiumCRL4WIG1ubiquitin ligase is critical for the formation of functional microtubule organisation centres in microgametocytes
Authors: Rashpa Ravish , Smith Cameron , Artavanis-Tsakonas Katerina , Brochet Mathieu 
Published: July 2023

AbstractMalaria is a mosquito-borne infectious disease caused by unicellular eukaryotic parasites of thePlasmodiumgenus. Protein ubiquitination by E3 ligases is a critical post-translational modification required for various cellular processes during the lifecycle ofPlasmodiumparasites. However, little is known about the repertoire and function of these enzymes inPlasmodium.Here we show thatPlasmodiumexpresses a conserved cullin RING E3 ligase (CRL) complex that is functionally related to the eukaryotic CRL4. InP. falciparumasexual blood stages, a cullin-4 scaffold interacts with the RING protein RBX1, the adaptor protein DDB1 and a set of putative receptor proteins that may determine substrate specificity for ubiquitination. These receptor proteins contain WD40-repeat domains and includeWD-repeat protein Important forGametogenesis 1 (WIG1). This CRL4-related complex is also expressed inP. bergheigametocytes, with WIG1 being the only putative receptor detected in both schizont and gametocyte stages. While WIG1 is not required for the proliferation ofP. bergheiasexual blood stages, its disruption leads to a complete block in microgamete formation. Proteomic analyses indicate thatWIG1disruption alters proteostasis of ciliary proteins and components of the DNA replication machinery during gametocytogenesis. Further analysis by ultrastructure expansion microscopy (U-ExM) indicates that WIG1-dependent depletion of ciliary proteins is associated with impaired formation of the microtubule organisation centres that coordinate mitosis with axoneme formation and altered DNA replication during microgametogenesis. This work identifies a CRL4-related ubiquitin ligase inPlasmodiumthat is critical for the transmission of malaria parasites by regulating proteostasis of ciliary and DNA replication proteins.
A neuropsychological basis for temptation-resistant voluntary exercise
Authors: Tesmer Alexander L. , Li Xinyang , Schmandt Cyra , Polania Rafael , Peleg-Raibstein Daria , Burdakov Denis 
Published: July 2023

SUMMARYDespite well-known health benefits of physical activity, many people under-exercise, and what drives prioritization of exercise over other alternatives is unclear. We implement a novel paradigm allowing to study how freely behaving mice rapidly display such prioritizing between time spent on wheel-running and other temptations such as palatable food. Causal manipulations and correlative analyses of underlying appetitive and consummatory psychobehavioral processes revealed this prioritizing to be instantiated by hypothalamic hypocretin/orexin neurons.
ThePlasmodium falciparumCCCH zinc finger protein MD3 regulates male gametocytogenesis through its interaction with RNA-binding proteins
Authors: Farrukh Afia , Musabyimana Jean Pierre , Distler Ute , Mahlich Vanessa Jil , Mueller Julius , Bick Fabian , Tenzer Stefan , Pradel Gabriele , Ngwa Che Julius 
Published: July 2023

AbstractMalaria transmission to mosquitoes is dependent on the formation of gametocytes. When fully matured, gametocytes are able to transform into gametes in the mosquito’s midgut, a process accompanied with their egress from the enveloping erythrocyte. Gametocyte maturation and gametogenesis require a well-coordinated gene expression programme that involves a wide spectrum of regulatory proteins, ranging from histone modifiers to transcription factors to RNA-binding proteins. Here, we investigated the role of the CCCH-zinc finger protein MD3 inP. falciparumgametocytogenesis. MD3 was originally identified by us as an epigenetically regulated protein of immature gametocytes and recently shown to be involved in male development in a barcode-based screen inP. berghei. We here show that MD3 is mainly present in the cytoplasm of immature maleP. falciparumgametocytes. Parasites deficient of MD3 are impaired in gametocyte maturation and male gametocyte exflagellation. BioID analysis in combination with co-immunoprecipitation assays unveiled an interaction network of MD3 with RNA-binding proteins like PABP1 and ALBA3, with translational initiators, regulators and repressors like elF4G, PUF1, NOT1 and CITH, and with other regulators of gametocytogenesis, including ZNF4, MD1 and GD1. We conclude that MD3 is part of a regulator complex crucial for post-transcriptional fine-tuning of male gametocytogenesis.
Deciphering the spatio-temporal transcriptional and chromatin accessibility of human retinal organoid development at the single cell level
Authors: Dorgau Birthe , Collin Joseph , Rozanska Agata , Boczonadi Veronika , Moya-Molina Marina , Hussain Rafiqul , Coxhead Jonathan , Dhanaseelan Tamil , Armstrong Lyle , Queen Rachel , Lako Majlinda 
Published: July 2023

AbstractMolecular information on the early stages of human retinal development remains scarce due to limitations in obtaining early human eye samples. Pluripotent stem cell-derived retinal organoids provide an unprecedented opportunity for studying early retinogenesis. Using a combination of single cell RNA-Seq and spatial transcriptomics we present for the first-time a single cell spatio-temporal transcriptome of retinal organoid development. Our data demonstrate that retinal organoids recapitulate key events of retinogenesis including optic vesicle/cup formation, formation of a putative ciliary margin zone, emergence of retinal progenitor cells and their orderly differentiation to retinal neurons. Combining the scRNA-with scATAC-Seq data, we were able to reveal cell-type specific transcription factor binding motifs on accessible chromatin at each stage of organoid development and to show that chromatin accessibility is highly correlated to the developing human retina, but with some differences in the temporal emergence and abundance of some of the retinal neurons.
Evaluating the bioactivities of natural and synthetic fungal tropolone sesquiterpenoids in various cell lines
Authors: Bergmann Timna C. , Menssen Max , Schotte Carsten , Cox Russell J. , Lee-Thedieck Cornelia 
Published: July 2023

ABSTRACTFungal specialized metabolites are known for their potent biological activities, among which tropolone sesquiterpenoids (TS) stand out for their diverse bioactivities. Here, we report bioactive effects of the recently discovered TS compounds 4–hydroxyxenovulene B and 4– dihydroxy norpycnidione, and the structurally related 4-hydroxy norxenovulene B and xenovulene B. Inhibition of metabolic activity after TS treatment was observed in Jurkat, PC–3 and FAIK3–5 cells, whereas MDA-MB-231 cells were unresponsive to treatment. Structurally similar epolones were shown to induce erythropoietin (EPO). Therefore, FAIK3-5 cells, which can naturally produce EPO, were applied to test the compounds in this regard. While no effect on EPO production in FAIK3-5 cells could be demonstrated, effects on their proliferation, viability, and morphology were observed depending on the presence of tropolone moieties in the molecules. Our study underlines the importance of relevant cell models for bioactivity testing of compounds with unknown mechanisms of action.
Multiple objects evoke fluctuating responses in several regions of the visual pathway
Authors: Schmehl Meredith N. , Caruso Valeria C. , Chen Yunran , Jun Na Young , Willett Shawn M. , Mohl Jeff T. , Ruff Douglas A. , Cohen Marlene , Ebihara Akinori F. , Freiwald Winrich , Tokdar Surya T. , Groh Jennifer M. 
Published: July 2023

AbstractHow neural representations preserve information about multiple stimuli is mysterious. Because tuning of individual neurons is coarse (for example, visual receptive field diameters can exceed perceptual resolution), the populations of neurons potentially responsive to each individual stimulus can overlap, raising the question of how information about each item might be segregated and preserved in the population. We recently reported evidence for a potential solution to this problem: when two stimuli were present, some neurons in the macaque visual cortical areas V1 and V4 exhibited fluctuating firing patterns, as if they responded to only one individual stimulus at a time. However, whether such an information encoding strategy is ubiquitous in the visual pathway and thus could constitute a general phenomenon remains unknown. Here we provide new evidence that such fluctuating activity is also evoked by multiple stimuli in visual areas responsible for processing visual motion (middle temporal visual area, MT), and faces (middle fundus and anterolateral face patches in inferotemporal cortex – areas MF and AL), thus extending the scope of circumstances in which fluctuating activity is observed. Furthermore, consistent with our previous results in the early visual area V1, MT exhibits fluctuations between the representations of two stimuli when these form distinguishable objects but not when they fuse into one perceived object, suggesting that fluctuating activity patterns may underlie visual object formation. Taken together, these findings point toward an updated model of how the brain preserves sensory information about multiple stimuli for subsequent processing and behavioral action.Impact StatementWe find neural fluctuations in multiple areas along the visual cortical hierarchy that could allow the brain to represent distinct co-occurring visual stimuli.
Modeling Type 1 Diabetes progression from single-cell transcriptomic measurements in human islets
Authors: Patil Abhijeet R. , Schug Jonathan , Liu Chengyang , Lahori Deeksha , Descamps Hélène C. ,   the Human Pancreas Analysis Consortium, Naji Ali , Kaestner Klaus H. , Faryabi Robert B. , Vahedi Golnaz 
Published: July 2023

AbstractType 1 diabetes (T1D) is a chronic condition in which the insulin-producing beta cells are destroyed by immune cells. Research in the past few decades characterized the immune cells involved in disease pathogenesis and has led to the development of immunotherapies that can delay the onset of T1D by two years. Despite this progress, early detection of autoimmunity in individuals who will develop T1D remains a challenge. Here, we evaluated the potential of combining single-cell genomics and machine learning strategies as a prime approach to tackle this challenge. We used gradient-boosting-based machine learning algorithms and modeled changes in transcriptional profiles of single cells from pancreatic tissues in T1D and nondiabetic organ donors collected by the Human Pancreas Analysis Program. We assessed whether mathematical modelling could predict the likelihood of T1D development in nondiabetic autoantibody-positive organ donors. While the majority of autoantibody-positive organ donors were predicted to be nondiabetic by our model, select donors with unique gene signatures were classified with the T1D group. Remarkably, our strategy also revealed a shared gene signature in distinct T1D associated models based on different cell types including alpha cells, beta cells and acinar cells, suggesting a common effect of the disease on transcriptional outputs of these cells. Together, our strategy presents the first report on the utility of machine learning algorithms in early detection of molecular changes in T1D.
The evolution of service toward automated customer assistance: there is a difference
Authors: Roberts Chris , Maier Thomas 
Published: July 2023

Purpose
The purpose of this paper is to explore the distinction between human-delivered service and technology-based, automated customer assistance.

Design/methodology/approach
This is a conceptual paper. There is no methodology.

Findings
The concept of service is primarily delivered when a human helps another. When technology is infused into the process and becomes the major component of delivering the aid that is requested, the process is automated customer assistance. Thus, “self-service” is not service. It is automated customer assistance.

Research limitations/implications
The definition of service is refined to describe the process of a human helping another person. When technology is used to provide the needed aid, it is no longer a service. Instead, it is automated customer assistance. The implication is that researchers should closely examine how users assess and perceive the two separate approaches to providing the needed aid.

Practical implications
The definition of service is refined to describe the process of a human helping another person. When technology is used to provide the needed aid, it is no longer a service. Instead, it is automated customer assistance. Researchers should closely examine how users assess and perceive the two separate approaches. Industry professionals should be mindful of the distinction between the delivery of service, which requires staff, and the provisioning of technology to provide assistance, which requires little to no staff. Intentionality should drive when customers are better helped by a human or by technology.

Originality/value
The value provided helps both providers create and users express when human-based service is needed versus assistance provided by technology.
Relevance of Stephen Covey's theory on the circle of life in the context of student decision-making to enroll for higher education
Authors: Srivastava Khusboo , Dhamija Somesh 
Published: July 2023

PurposeThis study attempts to elucidate the role of key influencers impacting the student decision-making process of enrollment for higher education in India from the lenses of Stephen Covey's theory on circles of life.Design/methodology/approachA sample of 556 students of Delhi NCR, India was selected based on a multi-staged sampling method. PLS-SEM was subsequently applied for statistical data analysis.FindingsThis quantitative finding voiced the relationships among the constructs in the proposed theoretical framework, i.e. Stephen Covey's circle of life theory. Additionally, it tinted the crucial role of “College attributes” in reconnoitering the relationship dynamics between key influencers (Circle of Influence and Circle of Concern) and student college choice (Circle of Control).Research limitations/implicationsThe present study incorporates only the first-year student population of undergraduate management courses in private universities from Delhi NCR, India limiting the generalization of findings substantially.Practical implicationsThe study garners the attention of education policymakers on the cognizance of the role played by parents and cohorts in driving the student's decision-making process of college choice under the circle of influence.Originality/valueThis study is pioneering research disseminating a comprehensive outlook of the circle of life theory of great Stephen Covey engrained upon a compendious conceptual model which enlightens the landscape of the decision-making process of student on enrollment under the influence of key influencers.
International entrepreneurship: an approach for entrepreneurial skill development
Authors: Sousa Maria José , Moreira Ana , Leão João , Sousa Miguel , Biancone Paolo Pietro , Lanzalonga Federico 
Published: July 2023

PurposeThe research aims to investigate the changing skills required for international entrepreneurship (IE) and the awareness of these skills among students and professionals in four European countries. The study intends to investigate students' and professionals' perceptions of entrepreneurial skills and the potential for educational programs to improve their awareness of these skills.Design/methodology/approachThis quantitative cross-sectional analysis uses an online questionnaire to collect data from 75 university students and 75 entrepreneurs in four European countries. Several tests validate the data, and Cronbach's alpha succeeded in measuring internal consistency. The results showed differences in the perception of skills between students and entrepreneurs.FindingsEntrepreneurs had developed all competencies except access to finance, while students had lower perceptions of their skills, except for collaboration. Students needed to improve significantly in access to finance, business planning, financial skills, knowledge of the labour market and digital marketing. Practitioners only required significant improvement in access to finance and digital marketing.Practical implicationsEducation programs should fit the needs of different groups: a broader program for students and more specific courses on access to finance and digital marketing for practitioners.Originality/valueThe present research's original feature highlights the need to monitor and adapt to the constantly changing skills for IE and the importance of hard and soft skills. The paper provides insights into the subject's awareness and perceived standard, with reflections for policymakers and practitioners.