bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimized tight binding between the S1 segment and KCNE3 is required for the constitutively open nature of the KCNQ1-KCNE3 channel complex
Authors: Kasuya Go , Nakajo Koichi 
Published: April 2021

AbstractTetrameric voltage-gated K+channels have four identical voltage sensor domains, and they regulate channel gating. KCNQ1 (Kv7.1) is a voltage-gated K+channel, and its auxiliary subunit KCNE proteins dramatically regulate its gating. For example, KCNE3 makes KCNQ1 a constitutively open channel at physiological voltages by affecting the voltage sensor movement. However, how KCNE proteins regulate the voltage sensor domain is largely unknown. In this study, by utilizing the KCNQ1-KCNE3-calmodulin complex structure, we thoroughly surveyed amino acid residues on KCNE3 and the S1 segment of the KCNQ1 voltage sensor facing each other. By changing the side-chain bulkiness of these interacting amino acid residues, we found that the distance between the S1 segment and KCNE3 is elaborately optimized to achieve the constitutive activity. In addition, we identified two pairs of KCNQ1 and KCNE3 mutants that partially restored constitutive activity by co-expression. Our work suggests that tight binding of the S1 segment and KCNE3 is crucial for controlling the voltage sensor domains.
Massively parallel pooled screening reveals genomic determinants of nanoparticle-cell interactions
Authors: Boehnke Natalie , Straehla Joelle P. , Safford Hannah C. , Kocak Mustafa , Rees Matthew G. , Ronan Melissa , Rosenberg Danny , Adelmann Charles H. , Chivukula Raghu R. , Nabar Namita , Berger Adam G. , Lamson Nicholas G. , Cheah Jaime H. , Li Hojun , Roth Jennifer A. , Koehler Angela N. , Hammond Paula T. 
Published: April 2021

AbstractTo accelerate the translation of cancer nanomedicine, we hypothesize that integrated genomic screens will improve understanding of the cellular processes governing nanoparticle trafficking. We developed a massively parallel high-throughput screening method leveraging barcoded, pooled cancer cell lines annotated with multi-omic data to investigate cell association patterns across a nanoparticle library spanning a range of formulations with clinical potential. This approach identified both the materials properties and cell-intrinsic features mediating nanoparticle-cell association. Coupling the data with machine learning algorithms, we constructed genomic nanoparticle trafficking networks and identified nanoparticle-specific biomarkers, including gene expression of SLC46A3. We engineered cell lines to validate SLC46A3 as a biomarker whose expression inversely predicts liposomal nanoparticle uptake bothin vitroandin vivo.We further demonstrated the predictive capabilities extend beyond liposomal nanoparticles, regulating both uptake and transfection efficacy of solid lipid nanoparticles. Our work establishes the power of massively parallel pooled cell screens for nanoparticle delivery and enables the identification and utilization of biomarkers to rationally design nanoformulations for specific patient populations.
Latent functional connectivity underlying multiple brain states
Authors: McCormick Ethan M. , Arnemann Katelyn L. , Ito Takuya , Hanson Stephen José , Cole Michael W. 
Published: April 2021

AbstractFunctional connectivity (FC) studies have predominantly focused on resting state, where ongoing dynamics are thought to reflect the brain’s intrinsic network architecture, which is thought to be broadly relevant because it persists across brain states (i.e., is state-general). However, it is unknown whether resting state is the optimal state for measuring intrinsic FC. We propose that latent FC, reflecting shared connectivity patterns across many brain states, better captures state-general intrinsic FC relative to measures derived from resting state alone. We estimated latent FC independently for each connection using leave-one-task-out factor analysis in 7 highly distinct task states (24 conditions) and resting state using fMRI data from the Human Connectome Project. Compared to resting-state connectivity, latent FC improves generalization to held-out brain states, better explaining patterns of connectivity and task-evoked activation. We also found that latent connectivity improved prediction of behavior outside the scanner, indexed by the general intelligence factor (g). Our results suggest that FC patterns shared across many brain states, rather than just resting state, better reflects state-general connectivity. This affirms the notion of “intrinsic” brain network architecture as a set of connectivity properties persistent across brain states, providing an updated conceptual and mathematical framework of intrinsic connectivity as a latent factor.
Comparative analyses of gene expression in common marmoset and human pluripotent stem cells (PSCs) identify factors enhancing homologous recombination efficiency in theHPRTlocus of human PSCs
Authors: Yoshimatsu Sho , Nakajima Mayutaka , Sanosaka Tsukasa , Sato Tsukika , Okano Hideyuki 
Published: April 2021

AbstractA previous study assessing the efficiency of the genome editing technology CRISPR-Cas9 for knock-in gene targeting in common marmoset (marmoset;Callithrix jacchus) embryonic stem cells (ESCs) unexpectedly identified innately enhanced homologous recombination (HR) activity in marmoset ESCs (cmESCs). Here, we compared gene expression in marmoset and human pluripotent stem cells (PSCs) using transcriptomic and quantitative PCR (qPCR) analyses and found that five HR-related genes (BRCA1, BRCA2, RAD51C, RAD51DandRAD51) were upregulated in marmoset cells. Four of these upregulated genes enhanced HR efficiency with CRISPR-Cas9 in human pluripotent stem cells. Thus, the present study provides a novel insight into species-specific mechanisms for the choice of DNA repair pathways.
Phenotypic heterogeneity is adaptive for microbial populations under starvation
Authors: Opalek Monika , Smug Bogna , Doebeli Michael , Wloch-Salamon Dominika 
Published: April 2021

AbstractTo persist in variable environments populations of microorganisms have to survive periods of starvation and be able to restart cell division in nutrient-rich conditions. Typically, starvation signals initiate a transition to a quiescent state in a fraction of individual cells, while the rest of the cells remain non-quiescent. It is widely believed that, while quiescent cells (Q) help the population to survive long starvation, the non-quiescent cells (NQ) are a side effect of imperfect transition. We analysed regrowth of starved monocultures of Q and NQ cells compared to mixed, heterogeneous cultures in simple and complex starvation environments. Our experiments, as well as mathematical modelling, demonstrate that Q monocultures benefit from better survival during long starvation, and from a shorter lag phase after resupply of rich medium. However, when the starvation period is very short, the NQ monocultures outperform Q and mixed cultures, due to their short lag phase. In addition, only NQ monocultures benefit from complex starvation environments, where nutrient recycling is possible. Our study suggests that phenotypic heterogeneity in starved populations could be a form of bet hedging, which is adaptive when environmental determinants, such as the length of the starvation period, the length of the regrowth phase, and the complexity of the starvation environment vary over time.ImportanceNon-genetic cell heterogeneity is present in glucose starved yeast populations in the form of quiescent (Q) and nonquiescent (NQ) phenotypes. There is evidence that Q cells help the population to survive long starvation. However, the role of the NQ cell type is not known, and it has been speculated that the NQ phenotype is just a side effect of imperfect transition to the Q phenotype. Here we show that, in contrast, there are ecological scenarios in which NQ cells perform better than monocultures of Q cells or naturally occuring mixed populations containing both Q and NQ. NQ cells benefit when the starvation period is very short and environmental conditions allow nutrient recycling during starvation. Our experimental and mathematical modeling results suggest a novel hypothesis: the presence of both Q and NQ phenotypes within starved yeast populations may reflect a form of bet hedging, where different phenotypes provide fitness advantages depending on environmental conditions.
Genetic and phenotypic heterogeneity inPNPT1,MYO15A,PTPRQandSLC12A2variants detected among hearing impaired assortative mating families in Southern India
Authors: Vanniya. S Paridhy , Chandru Jayasankaran , Jeffrey Justin Margret , Rabinowitz Tom , Brownstein Zippora , Krishnamoorthy Mathuravalli , Avraham Karen B. , Cheng Le , Shomron Noam , Srisailapathy C. R. Srikumari 
Published: April 2021

AbstractExome analysis was used to resolve the etiology of hearing loss (HL) in four South Indian assortative mating families. Six variants, including three novel ones, were identified in four genes:PNPT1p.Ala46Gly and p.Asn540Ser,MYO15Ap.Leu1485Pro and p.Tyr1891*,PTPRQp.Gln1336*, andSLC12A2p.Pro988Ser. Compound heterozygousPNPT1variants were associated with prelingual profound sensorineural hearing loss (SNHL), vestibular dysfunction and unilateral progressive vision loss in one family. In the second family,MYO15Avariants in the myosin motor domain, including a novel variant, were found to be associated with prelingual profound SNHL. A novelPTPRQvariant was associated with postlingual progressive sensorineural/mixed HL and vestibular dysfunction in the third family, with mastoid bone hypopneumatization observed in one family member. In the fourth family, theSLC12A2novel variant was found to segregate with severe-to-profound HL causing DFNA78, across three generations. Our results suggest a high level of allelic, genotypic and phenotypic heterogeneity of HL in these families. This study is the first to report the association ofPNPT1,PTPRQandSLC12A2variants with HL in the Indian population.
The viral vectored vaccine targeting Thymosin β10 controls tumour growth in a murine model of prostate cancer
Authors: Cappuccini Federica , Mueller Julius , Pollock Emily , Hill Adrian VS , Ternette Nicola , Redchenko Irina 
Published: April 2021

AbstractDirect analysis of MHC-presented antigens by mass spectrometry has been successfully applied for the evaluation of the antigenic landscape of different human tissues and malignancies in the past. In the current study, for the first time this approach has been applied to investigate a murine prostate cancer peptidome for the development of next generation prostate cancer vaccines using the TRansgenic Adenocarcinoma of Mouse Prostate, TRAMP, model. We have performed immunopeptidomic analysis of the normal mouse prostate and mouse prostate adenocarcinoma samples and identified a number of peptides overexpressed on tumour tissue compared to the normal prostate. We selected two of these proteins previously reported to play a role in carcinogenesis, thymosin beta 4 (Thyβ4) and thymosin beta 10 (Thyβ10), expressed them in the chimpanzee adenovirus (ChAdOx1) and Modified Vaccinia Ankara (MVA) recombinant viral vectors and evaluated these constructs as a candidate prostate cancer vaccine in a murine prostate cancer model. We have found that the vaccine encoding the Thyβ10 polypeptide tethered to the MHC class II associated invariant chain, CD74, significantly delayed outgrowth of established tumours in an ectopic TRAMP-C1 mouse model of prostate cancer. The observed tumour-protective efficacy was not associated with Thyβ10-specific cellular or antibody responses, suggesting an existence of other mechanisms underlying anti-tumour effect in this model that are yet to be elucidated.
Structure of the Bacteriophage PhiKZ non-Virion RNA Polymerase
Authors: de Martín Garrido Natàlia , Orekhova Mariia , Lai Wan Loong Yuen Ting Emilie , Litvinova Anna , Ramlaul Kailash , Artamonova Tatyana , Melnikov Alexei S. , Serdobintsev Pavel , Aylett Christopher H. S. , Yakunina Maria 
Published: April 2021

AbstractBacteriophage ΦKZ is the founding member of a family of massive bacterial viruses. It is considered to have therapeutic potential as its host,Pseudomonas aeruginosa, is an opportunistic, intrinsically antibiotic resistant, pathogen that kills tens of thousands worldwide each year. ΦKZ is an incredibly interesting virus, expressing many systems the host already possesses. On infection, it forms a “nucleus”, erecting a barrier around its massive genome to exclude host restriction endonucleases and CRISPR-Cas systems. ΦKZ infection is independent of the host transcriptional apparatus. It expresses two different multi-subunit RNA polymerases (RNAPs): the virion RNAP (vRNAP) is injected with the viral DNA during infection to transcribe early genes, including those encoding the non-virion RNAP (nvRNAP), which transcribes all further genes. ΦKZ nvRNAP is formed by four polypeptides thought to represent homologues of the eubacterial β/β′ subunits, and a fifth with unclear homology, but essential for transcription. We have resolved the structure of ΦKZ nvRNAP to 3.3 Å, shedding light on its assembly, homology, and the biological role of the fifth subunit: it is an embedded, integral member of the complex, with structural homology and a biochemical role implying that it has evolved from an ancestral homologue to σ-factor.
Aircraft control with the use of model reference adaptive control
Authors: Kopecki Grzegorz Henryk 
Published: April 2021

Purpose
Indirect (fly-by-wire) control systems for general aviation aircraft and unmanned aircraft vehicles (UAV) control systems enable the decoupling of control surfaces. This method of aircraft control is different from classical approach. The purpose of the article is to show the aircraft can be controlled even if the control control surfaces are blocked.

Design/methodology/approach
The concept discussed here relies on model reference adaptive control. The approach presented requires modifications of aircraft linearized model. In this paper, an example of roll angle control is shown.

Findings
During simulations the system worked properly with control surfaces partially blocked, if the blockage appeared close to neutral position. Exemplary simulations are shown in the text.

Practical implications
The solution presented was implemented on a UAV autopilot. Hardware in the loop simulations were performed, which shows the potential of practical usage.

Originality/value
Aircraft control, as discussed in this paper, gives the possibility of aircraft control and stable flight before a fault is detected, which increases the safety level.
Preservation of rare documentary sources in private libraries and religious institutions
Authors: Lone Mohammad Ishaq , Wahid Abdul , Shakoor Abdul 
Published: April 2021

Purpose
The study is an endeavour to find out the preservation status of rare documents in Srinagar. The rare documents, here, mean the manuscripts and rare books, journals, reports, magazines, archival documents, etc. These resources are available in private libraries of individuals and religious institutions in Srinagar. This study aims to find these private libraries of individuals/families and religious institutions, which are unknown to the scholarly world and observe the preservation status of rare documents. The main focus is to document their present preservation status to give an opportunity to the stakeholders, particularly the government organizations, to take appropriate action before they are lost forever.

Design/methodology/approach
Before conducting the survey, the investigator interviewed 114 persons including literary persons, faith leaders, librarians, faculty members from various prominent institutions in Srinagar to get leads regarding the persons/families and religious institutions in possession of rare documents. The investigator gathered data through two different schedules and later analyzed the same in this study after carrying out a pilot study to make necessary changes to the schedules compiled for the study. The investigator visited personally each family/individual and religious institution to gather the data for months together.

Findings
An arduous job was carried out in which around 111 individuals/families and religious institutions were found to be having such rare resources. However, the data gathered reveals a dismal picture of private libraries and religious institutions, in possession of rare documents, as almost all caretakers/ families are devoid of any knowledge regarding the maintenance of these important sources of knowledge. Further, the traditional methods of preservation are still in vogue in some private libraries. These traditional methods have opened new areas of research while at the same time can prove detrimental to the collection if they are useless.

Originality/value
The study is the first of its kind in the summer capital of Jammu and Kashmir i.e. Srinagar. The study gives an idea of preservation status of manuscripts and rare documents including books, magazines, journals, archival documents, etc. so that the same are taken care of for posterity. The study is an eye-opener for the policymakers, conservators, archivists and others interested in historical documents. The study will help in furthering the research process as it needs to be ascertained whether the traditional methods of preservation are fruitful. In short, the study is quite helpful in understanding the nature of collection in Srinagar so that appropriate steps are taken by all particularly the Government in J&K. The paper will surely help in the policy formulation in the future.
Exploring and extending the synergy concept – a study of three acquisitions
Authors: Holtström Johan , Anderson Helén 
Published: April 2021

Purpose
This study aims to contribute with an extended framework on synergy realisation in acquisitions. The study conceptualises synergy realisation after acquisitions, in interaction with other companies in a business network and that synergy can be the result of both intended and not intended actions.

Design/methodology/approach
The study is based on a company involved in acquisitions, being both the acquirer and the acquired. The data for analysis were collected through semi-structured interviews with managers involved in the described acquisition processes. The semi-structured interviews were guided by overarching themes to cover relevant areas of the described acquisitions.

Findings
This study develops a framework in which synergy is used as a concept in business networks. The framework offers a more dynamic perspective on acquisition processes and extends the view of acquisition performance beyond more financial and company internal aspects of acquisition processes. Further, the findings show that related companies such as customers and suppliers, play important roles in synergy realisation.

Practical implications
From a managerial perspective, the study shows the importance of understanding the underlying forces of integration processes.

Originality/value
The concept of synergy used in this study not only includes the companies integrated in an acquisition but also their business networks. Including the integrated companies and their business networks provides a more dynamic perspective from which to plan and realise synergy.
Rural women characteristics and sustainable entrepreneurial intention: a road to economic growth in Bangladesh
Authors: Polas Mohammad Rashed Hasan , Raju Valliappan , Muhibbullah Md , Tabash Mosab I. 
Published: April 2021

PurposeThis study aims to provide a better understanding of the individual-level factors that affect rural women’s sustainable entrepreneurial intention in starting and running a business in Bangladesh and contributing to national economic growth.Design/methodology/approachData from a sample of 297 rural Bangladeshi women were analysed using a quantitative approach with Smart PLS 3.0 (SEM) and SPSS V25. This was to explore the direct influence of perceived capability, social perception and individual competencies on women’s intention to become sustainable entrepreneurs. The indirect consequences of these three variables on perceived opportunity were also evaluated.FindingsThe studies confirmed a positive and significant association between perceived capability and social perception with the intention to become a sustainable entrepreneur. There is no conventional connection between women’s individual competencies and their intention to become an entrepreneur. Moreover, the data confirmed that perceived opportunity mediates the relationship between perceived capability and individual competencies with the intention to become an entrepreneur. However, no mediation role of perceived opportunity in the relationship between social perception and intention was found.Originality/valueThis study is one of very few to explore through empirical analysis the relationship between women’s individual characteristics and their intention to become sustainable entrepreneurs and to investigate whether rural women are motivated to become empowered to contribute to economic development through sustainable entrepreneurial intention.
An AHP analysis of scientometrically derived factors of entrepreneurial intentions of women and constructing a conceptual research framework
Authors: Patra Bhairab Chandra , Lenka Usha 
Published: April 2021

PurposeThe purpose of this study is to analyze the entrepreneurial intentions (EI) of women to better understand the cognition process of women which will help to identify the reason for their inadequate participation in the field of entrepreneurship.Design/methodology/approachThis study follows the method of a traditional literature survey followed by scientometric analysis to identify the primary factors to the EI of women. The factors obtained from the literature review were provided to the nominal group, and the process of nominal group technique (NGT) was carried out to frame a research framework. The factors were then ranked based on their significance using the analytic hierarchy process (AHP), taking into consideration the review of experts.FindingsAmong the primary factors, personal factors were found to be the most influential factors and weighted 54%. Self-efficacy was found to be the most prominent secondary variable and had a global weight of 22.14%.Research limitations/implicationsThe research outcome has implications for policymaking bodies, investors, academicians and potential women entrepreneurs. Future researchers can apply exploratory research methods and confirmatory research methods to test the research framework.Originality/valueVery few researchers have used the technique of scientometric analysis for the review of literature on EI of women, and to the best of the authors’ knowledge, no earlier researcher has attempted to use the technique of NGT or AHP after scientometric analysis.