bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal identification of single-cell experimental perturbation effects with CINEMA-OT
Authors: Dong Mingze , Wang Bao , Wei Jessica , de O. Fonseca Antonio H. , Perry Curt , Frey Alexander , Ouerghi Feriel , Foxman Ellen F. , Ishizuka Jeffrey J. , Dhodapkar Rahul M. , van Dijk David 
Published: August 2022

AbstractRecent advancements in single-cell technologies allow characterization of experimental perturbations at single-cell resolution. While methods have been developed to analyze such experiments, the application of a strict causal framework has not yet been explored for the inference of treatment effects at the single-cell level. In this work, we present a causal inference based approach to single-cell perturbation analysis, termed CINEMA-OT (Causal INdependent Effect Module Attribution + Optimal Transport). CINEMA-OT separates confounding sources of variation from perturbation effects to obtain an optimal transport matching that reflects counterfactual cell pairs. These cell pairs represent causal perturbation responses permitting a number of novel analyses, such as individual treatment effect analysis, response clustering, attribution analysis, and synergy analysis. We benchmark CINEMA-OT on an array of treatment effect estimation tasks for several simulated and real datasets and show that it outperforms other single-cell perturbation analysis methods. Finally, we perform CINEMA-OT analysis of two newly-generated datasets: (1) rhinovirus and cigarette smoke-exposed airway organoids, and (2) combinatorial cytokine stimulation of immune cells. In these experiments, CINEMA-OT reveals potential mechanisms by which cigarette smoke exposure dulls the airway antiviral response, as well as the logic that governs chemokine secretion and peripheral immune cell recruitment.
CRISPR comparison toolkit (CCTK): Rapid identification, visualization, and analysis of CRISPR array diversity
Authors: Collins Alan J. , Whitaker Rachel J. 
Published: August 2022

AbstractCRISPR-Cas systems provide immunity against mobile genetic elements (MGEs) through sequence-specific targeting by spacer sequences encoded in CRISPR arrays. Spacers are highly variable between microbial strains and can be acquired rapidly, making them well suited for use in strain typing of closely related organisms. However, the historical record of spacer acquisitions and deletions represented by arrays has not previously been used to reconstruct strain histories. We therefore developed the CRISPR Comparison Toolkit (CCTK) to enable analyses of array relationships. CCTK includes tools to identify arrays, analyze relationships between arrays using CRISPRdiff and CRISPRtree, and predict targets of spacers. CRISPRdiff visualizes arrays and highlights the similarities between them. CRISPRtree infers a phylogenetic tree from array relationships and presents a hypothesis of the evolutionary history of the arrays. CCTK unifies several CRISPR analysis tools into a single command line application, including the first tool to infer phylogenies from array relationships.
Comprehensive isotopomer analysis of glutamate and aspartate in small tissue samples
Authors: Cai Feng , Bezwada Divya , Cai Ling , Mahar Rohit , Wu Zheng , Pachnis Panayotis , Yang Chendong , Kelekar Sherwin , Gu Wen , Vu Hieu S. , Mathews Thomas P. , Zacharias Lauren G. , Martin-Sandoval Misty , Do Duyen , Oaxaca K. Celeste , Jin Eunsook S. , Margulis Vitaly , Malloy Craig R. , Merritt Matthew E. , DeBerardinis Ralph J. 
Published: August 2022

SUMMARYStable isotopes are powerful tools to assess metabolism.13C labeling is detected using nuclear magnetic resonance spectroscopy (NMRS) or mass spectrometry (MS). MS has excellent sensitivity but generally cannot discriminate among different13C positions (isotopomers), whereas NMRS is less sensitive but reports some isotopomers. Here, we develop an MS method that reports all 16 aspartate and 32 glutamate isotopomers while requiring 1% of the sample used for NMRS. This method discriminates between pathways that result in the same number of13C labels in aspartate and glutamate, providing enhanced specificity over conventional MS. We demonstrate regional metabolic heterogeneity within human tumors, document the impact of fumarate hydratase deficiency in human renal cancers, and investigate the contributions of TCA cycle turnover and CO2recycling to isotope labeling in vivo. This method can accompany NMRS or standard MS to provide outstanding sensitivity in isotope labeling experiments, particularly in vivo.
Type 17 Follicular Helper T (Tfh17) Cells are Superior for Memory Maintenance
Authors: Gao Xin , Luo Kaiming , Wang Diya , Wei Yunbo , Yao Yin , Deng Jun , Yang Yang , Zeng Qunxiong , Dong Xiaoru , Xiong Le , Gong Dongcheng , Lin Lin , Pohl Kai , Liu Shaoling , Liu Yu , Liu Lu , Nguyen Thi H. O. , Allen Lilith F. , Kedzierska Katherine , Jin Yanliang , Du Meirong , Chen Wanping , Lu Liangjing , Shen Nan , Liu Zheng , Cockburn Ian A. , Luo Wenjing , Yu Di 
Published: August 2022

AbstractA defining feature of successful vaccination is the ability to induce long-lived antigen- specific memory cells. Follicular helper T (Tfh) cells specialize in providing help to B cells in mounting protective humoral immunity in infection and after vaccination. Memory Tfh cells that retain the CXCR5 expression can confer protection through enhancing humoral response upon antigen re-exposure but how they are maintained is poorly understood. CXCR5+memory Tfh cells in human blood are divided into Tfh1, Tfh2 and Tfh17 cells by the expression of chemokine receptors CXCR3 and CCR6 associated with Th1 and Th17 respectively. Here, we developed a new method to induce Tfh1, Tfh2 and Tfh17-like (iTfh1, iTfh2 and iTfh17) cellsin vitro. Although all three iTfh subsets efficiently support antibody responses in recipient mice with immediate immunization, iTfh17 cells are superior to iTfh1 and iTfh2 cells in supporting antibody response to a later immunization after extended restingin vivoto mimic memory maintenance. Notably, the counterpart human Tfh17 cells are selectively enriched in CCR7+central memory Tfh (TfhCM) with survival and proliferative advantages. Furthermore, the analysis of multiple human cohorts that received different vaccines for HBV, influenza virus, tetanus toxin or measles revealed that vaccine-specific Tfh17 cells outcompete Tfh1 or Tfh2 cells for the persistence in memory phase. Therefore, the complementary mouse and human results showing the advantage of Tfh17 cells in maintenance and memory function supports the notion that Tfh17-induced immunization might be preferable in vaccine development to confer long-term protection.
Two shifts in evolutionary lability underlie independent gains and losses of root-nodule symbiosis in a single clade of plants
Authors: Kates Heather R. , O’Meara Brian C. , LaFrance Raphael , Stull Gregory W. , James Euan K. , Conde Daniel , Liu Shuiyin , Tian Qin , Yi Tingshuang , Kirst Matias , Ané Jean-Michel , Soltis Douglas E. , Guralnick Robert P. , Soltis Pamela S. , Folk Ryan A. 
Published: August 2022

AbstractRoot nodule symbiosis (RNS) allows plants to access atmospheric nitrogen converted into usable forms through a mutualistic relationship with soil bacteria. RNS is a complex trait requiring coordination from both the plant host and the bacterial symbiont, and pinpointing the evolutionary origins of root nodules is critical for understanding the genetic basis of RNS. This endeavor is complicated by data limitations and the intermittent presence of RNS in a single clade of ca. 30,000 species of flowering plants, i.e., the nitrogen-fixing clade (NFC). We developed the most extensivede novophylogeny for all major lineages of the NFC and an enhanced root nodule trait database to reconstruct the evolution of RNS. Through identification of the evolutionary pathway to RNS gain, we show that shifts among heterogeneous evolutionary rates can explain how a complex trait such as RNS can arise many times across a large phylogeny. Our analysis identifies a two-step process in which an ancestral precursor state gave rise to a more labile state from which RNS was quickly gained at specific points in the NFC. Our rigorous reconstruction of ancestral states illustrates how a two-step pathway could have led to multiple independent gains and losses of RNS, contrary to recent hypotheses invoking just a single gain and numerous losses. RNS may be an example of multi-level convergent evolution, thus requiring a broader phylogenetic and genetic scope for genome-phenome mapping to elucidate mechanisms enabling fully functional RNS.
Body mass index in parents and their adult offspring: a systematic review and meta-analysis
Authors: Zhang Jie , Clayton Gemma , Overvad Kim , Olsen Anja , Lawlor Deborah A , Dahm Christina C 
Published: August 2022

SummaryObesity may track across generations, due to genetics and family environmental factors, or possibly intrauterine programming. However, many studies only assess associations between maternal body mass index (BMI) on offspring obesity in childhood. To determine whether maternal and paternal associations with offspring BMI differ, and whether associations persist into adulthood, a systematic review and meta-analysis was done. MEDLINE, EMBASE and PubMed (to December 2019) were searched. Observational studies reporting associations between maternal or paternal BMI and adult offspring BMI were included. Offspring BMIs were reported as continuous or categorical measures. 46 studies were included in the systematic review. Meta-analyses were conducted using random effects models. Parental BMI was positively associated with offspring BMI in adulthood. The pooled mother-offspring standardized mean difference (SMD) was 0.23 (95% confidence interval (CI): 0.20, 0.26), and father-offspring SMD was similar: 0.22 (95%CI: 0.19, 0.25) in adjusted models. Maternal and paternal overweight and obesity were associated with higher offspring BMI with similar magnitudes. If these associations are causal, they support interventions targeting all family members, rather than focusing solely on mothers, to maintain a healthy weight.
HSDatabase – a database of highly similar duplicate genes from plants, animals, and algae
Authors: Zhang Xi , Hu Yining , Smith David Roy 
Published: August 2022

AbstractGene duplication is an important evolutionary mechanism capable of providing new genetic material, which can help organisms adapt to various environmental conditions. Recent studies, for example, have indicated that highly similar duplicated genes (HSDs) are involved in adaptation to extreme conditions via gene dosage. However, HSDs in most genomes remain uncharacterized. Here, we collected and curated HSDs in nuclear genomes from a diversity of species and indexed them in an online, open-access sequence repository called HSDatabase. Currently, this database contains 117,864 curated HSDs from 40 eukaryotic genomes, and it includes information on the total HSD number, gene copy number/length, and alignments of gene copies. HSDatabase also allows users to download sequences of gene copies, access genome browsers, and link out to other databases, such as Pfam and KEGG. What’s more, a built-in Basic Local Alignment Search Tool (BLAST) option is available to conveniently explore potential homologous sequences of interest within and across species. HSDatabase is presented with a user-friendly interface and provides easy access to the source data. It can be used on its own for comparative analyses of gene duplicates or in conjunction with HSDFinder, a newly developed bioinformatics tool for identifying, annotating, categorizing, and visualizing HSDs.Database URLhttp://hsdfinder.com/database/
Hierarchical Interleaved Bloom Filter: Enabling ultrafast, approximate sequence queries
Authors: Mehringer Svenja , Seiler Enrico , Droop Felix , Darvish Mitra , Rahn René , Vingron Martin , Reinert Knut 
Published: August 2022

AbstractSearching sequences in large, distributed databases is the most widely used bioinformatics analysis done. This basic task is in dire need for solutions that deal with the exponential growth of sequence repositories and perform approximate queries very fast.In this paper, we present a novel data structure: the Hierarchical Interleaved Bloom Filter (HIBF). It is extremely fast and space efficient, yet so general that it has the potential to serve as the underlying engine for many applications.We show that the HIBF is superior in build time, index size and search time while achieving a comparable or better accuracy compared to other state-of-the art tools (Mantis and Bifrost). The HIBF builds an index up to 211 times faster, using up to 14 times less space and can answer approximate membership queries faster by a factor of up to 129. This can be considered a quantum leap that opens the door to indexing complete sequence archives like the European Nucleotide Archive or even larger metagenomics data sets.
Structural Mechanisms of Actin Isoforms
Authors: Arora Amandeep S. , Huang Hsiang-Ling , Singh Ramanpreet , Narui Yoshie , Suchenko Andrejus , Hatano Tomoyuki , Heissler Sarah M. , Balasubramanian Mohan K. , Chinthalapudi Krishna 
Published: August 2022

AbstractActin isoforms organize into distinct networks that are essential for the normal function of eukaryotic cells. Despite a high level of sequence and structure conservation, subtle changes in their design principles determine the interaction with myosin motors and actin-binding proteins. The functional diversity is further increased by posttranslational modifications (PTMs). Therefore, identifying how the structure of actin isoforms relates to function is important for our understanding of normal cytoskeletal physiology. Here, we report the high-resolution structures of filamentous skeletal α-actin (3.37Å), cardiac α-actin (3.07Å), ß-actin (2.99Å), and γ-actin (3.38Å) in the Mg2+·ADP state with their native PTMs. The structures revealed isoform-specific conformations of the N-terminus that shifts closer to the filament surface upon myosin binding, thereby establishing isoform-specific interfaces. Retropropagated structural changes further show that myosin binding modulates actin filament structure. Further, our structures enabled us to reveal the location of disease-causing mutations and to analyze them with respect to known locations of PTMs. Collectively, the previously unknown structures of single-isotype, posttranslationally modified bare cardiac α-actin, ß-actin, and γ-actin reveal general principles, similarities, and differences between isoforms. They complement the repertoire of known actin structures and allow for a comprehensive understanding of in vitro and in vivo functions of actin isoforms.
On the test of novel constitutive relation of capacitor for electrical circuit analysis: a fractal calculus-based approach
Authors: Banchuin Rawid 
Published: August 2022

Purpose
The purpose of this paper is to test the capability to properly analyze the electrical circuits of a novel constitutive relation of capacitor.

Design/methodology/approach
For ceteris paribus, the constitutive relations of the resistor and inductor have been reformulated by following the novel constitutive relation of capacitor. The responses of RL, RC, LC and RLC circuits defined on the fractal set described by these definitions have been derived by means of the fractal calculus and fractal Laplace transformation. A comparative Hamiltonian formalism-based analysis has been performed where the circuits described by the conventional and the formerly proposed revisited constitutive relations have also been considered.

Findings
This study has found that the novel constitutive relations give unreasonable results unlike the conventional ones. Like such previous revisited constitutive relations, an odd Hamiltonian has been obtained. On the other hand, the conventional constitutive relations give a reasonable Hamiltonian.

Originality/value
To the best of the author’s knowledge, for the first time, the analysis of fractal set defined electrical circuits by means of unconventional constitutive relations has been performed where the deficiency of the tested capacitive constitutive relation has been pointed out.
Combining transaction characteristics and governance mechanisms to suppress opportunism in construction projects: qualitative comparative analysis
Authors: Guo Wenqian , Lu Wenxue , Kang Fei 
Published: August 2022

PurposeThe understanding of how to mitigate opportunism in construction projects is still limited and conflicting. The complexity of causalities and interdependence among antecedents of opportunism (transaction characteristics and governance mechanisms) is the major obstacle to current research. This study takes a holistic perspective to explore the different combinations of conditions that lead to high opportunism and low opportunism in project management.Design/methodology/approachThrough 2 phases of the interview and questionnaire survey, the 91 valid survey data were collected from the buyer–seller relationships in construction projects and analyzed by adopting fuzzy-set qualitative comparative analysis.FindingsA single transaction characteristic is rarely sufficient to explain opportunism, and combinations of different transaction characteristics and governance mechanisms (performance ambiguity, asset specificity, buyer's requirement certainty, informal control, and formal control) have different effects on opportunism. In the case of extremely unsatisfactory transaction characteristics, even the combination of formal and informal control cannot prevent high opportunism. The combination including low-formal control and high-asset specificity easily leads to high opportunism. Besides, performance ambiguity is a vital factor in mitigating high opportunism or achieving low opportunism.Originality/valuePrevious studies have always addressed the role of one or some factors independently and separately. This study is one of the first to explore the different combinations of conditions that result in high opportunism and low opportunism in project management based on transaction costs economics and agency theory.
Does generation matter to innovation development? A new look at entrepreneurial businesses from the perspective of resource-based view (RBV)
Authors: Kariv Dafna , Cisneros Luis , Kashy-Rosenbaum Gaby , Krueger Norris 
Published: August 2022

PurposeResearch shows that innovation is imperative for business competitiveness and that entrepreneurs are stimulators of innovation. This is particularly true for younger entrepreneurs, who are recognized as having technological savvy, high dependency on the web, low fear of change and high zeal for challenges. However, not all businesses headed by younger entrepreneurs innovate, and research on younger entrepreneurs' innovation is lacking. This study assessed the main drivers of innovation in a sample of young Canadian entrepreneurs leading businesses in the initiation phase.Design/methodology/approachA sample of young Canadian entrepreneurs leading businesses in the initiation phase has been employed. This study is based on younger entrepreneurs and draws on the definition of generations Y and Z (Taylor and Keeter, 2010). It examines the initial stage of a business, up to 3 years. The sample includes 100 adults (65% female), whose ages ranged from 18 to 34 years. The drivers to innovate included external support (e.g. mentoring, funds, accelerators) and internal factors, including psychological attributes (i.e. risk-taking) and entrepreneurial motivations. Regression and structural equation modeling analyses have been conducted.FindingsThe findings revealed that entrepreneurial motivations for achieving self-fulfillment and contributing to the world, which are prevalent among younger generations, fostered innovation both directly and indirectly through the mediating effect of external support and risk-taking. External support fostered innovation not directly but through the mediating effect of risk-taking; in contrast, internal factors directly propelled innovation. This finding demonstrates the significance younger generations attribute to internal factors over external factors in the quest for innovation.Practical implicationsThis study can be an intriguing starting point for future studies to examine in more depth the intertwined role of external and internal factors in accelerating innovation among younger entrepreneurs. Studies could examine various psychological attributes and professional and business capabilities (Zahra, 2021) as well as external factors.Originality/valueOur findings add to this literature in stressing the need to strengthen risk-taking among younger entrepreneurs, which is affected by external support and produces innovation; and reinforce the relevance of the resource-based view in revealing younger entrepreneurs' avenues to develop innovation, pinpointing external support as contingent on motivation and demonstrating the role of risk-taking in the pursuit of innovation.
Knowledge creation in projects: an interactive research approach for deeper business insight
Authors: Engström Annika , Johansson Anette , Edh Mirzaei Nina , Sollander Kristina , Barry Daved 
Published: August 2022

PurposeThe purpose of this paper is to shed light on different types of knowledge created and how this links to the project design, process, and content.Design/methodology/approachIn this paper the authors investigate participants' experiences from a three-year interactive research project, designed to trigger reflection among the participants. They apply a knowledge creation perspective on experiences expressed by participants as a result of different research project activities.FindingsThe study resulted in five categories of insights with potential for sustainable influence on the participating organizations: an understanding of concepts and theories; an understanding of the impacts of collaborative, reflective work processes; an understanding of the meaning of one's own organizational context; an understanding of the importance of increased organizational self-awareness; and an understanding of the potential for human interaction and communication.Practical implicationsThe author’s findings suggest that it is possible to design a project to promote more profound and sustainable effects on a business beyond the explicit purpose of the project. They advise practitioners to make room for iterative reflection; be mindful to create a trustful and open environment in the team; challenge results with opposing views and theories; and make room for sharing experiences and giving feedback.Originality/valueThis study contributes to unraveling key practices which can nurture conditions for knowledge creation in interactive research projects and business projects alike.