bluuebunny/crossref_metadata_2025_split huggingface dataset:
LIS1 RNA-binding orchestrates the mechanosensitive properties of embryonic stem cells in AGO2-dependent and independent ways
Authors: Kshirsagar Aditya , Gorelik Anna , Olender Tsviya , Sapir Tamar , Tsuboi Daisuke , Rosenhek-Goldian Irit , Malitsky Sergey , Itkin Maxim , Argoetti Amir , Mandel-Gutfreund Yael , Cohen Sidney R. , Hanna Jacob , Ulitsky Igor , Kaibuchi Kozo , Reiner Orly 
Published: March 2022

AbstractLissencephaly-1(LIS1) is associated with neurodevelopmental diseases and is known to regulate the activity of the molecular motor cytoplasmic dynein. Here we show that LIS1 is essential for the viability of mouse embryonic stem cells (mESCs), and it regulates the physical properties of these cells. LIS1 dosage substantially affects gene expression, and we uncovered an unexpected interaction of LIS1 with RNA and RNA-binding proteins, most prominently the Argonaute complex. We demonstrate that LIS1 overexpression partially rescued the expression of extracellular matrix (ECM) and mechanosensitive genes conferring stiffness to Argonaute null mESCs. Collectively, our data transforms the current perspective on the roles of LIS1 in post- transcriptional regulation underlying development and mechanosensitive processes.
The oxytocin system regulates tearing
Authors: Nakamura Shigeru , Imada Toshihiro , Jin Kai , Shibuya Michiko , Sakaguchi Hisayo , Izumiseki Fumiya , Tanaka Kenji F , Mimura Masaru , Nishimori Kastuhiro , Kambara Natsumi , Hirayama Nozomi , Kamimura Itsuka , Nomoto Kensaku , Mogi Kazutaka , Kikusui Takefumi , Mukai Yasutaka , Yamanaka Akihiro , Tsubota Kazuo 
Published: March 2022

AbstractTears are an exocrine physiological fluid secreted onto the ocular surface from the lacrimal apparatus in all mammals. Limited research has been conducted on the functional neuronal circuitry of tear production. In particular, the neuronal mechanisms of emotional tearing, which is a physiological reaction harmonized with enhanced emotional arousal and assumed to be unique to humans, remain unclear. We identified that the oxytocin neurons in the paraventricular hypothalamus is functionally projected to the oxytocin receptor-expressing neurons in the lacrimation center of the superior salivatory nucleus. Optogenetic activation or inhibition of these neurons and/or receptors can modulate the superior salivatory nucleus dependent tear secretion mediated through oxytocin. Moreover, we identified that maternal behavior, nociceptive behavior stimulation, and aversive memory retrieval are linked to tearing in mice, and that these emotional linked tearing are suppressed by optogenetic inhibition of the corresponding oxytocin system. Thus, tearing could be regulated through functional connections between central oxytocin systems in the paraventricular hypothalamus and the superior salivatory nucleus.
Ontogeny of superorganisms: Social control of queen specialization in ants
Authors: Majidifar Vahideh , Psalti Marina N. , Coulm Martin , Fetzer Ebru , Teggers Eva-Maria , Rotering Frederik , Grünewald Judith , Mannella Luca , Reuter Maxi , Unte Dennis , Libbrecht Romain 
Published: March 2022

AbstractA central question in life sciences is to understand the ontogeny of biological systems, which exist at multiple phenotypic scales and function via the cooperation of specialized entities. Examples of such systems include multicellular organisms, which consist of specialized cells, and insect societies (or superorganisms), which are composed of specialized individuals. Both systems are products of major evolutionary transitions, and they share commonalities in their ontogeny, as both develop from a single, pluripotent unit. While the ontogeny of multicellular organisms is well understood, the factors and mechanisms that control the ontogeny of superorganisms remain poorly studied. Here, we report experimental investigations of the process of colony foundation in ants. In most ant species, a new colony is established by a solitary founding queen that expresses behavioral pluripotency to produce the first workers, at which point the queen becomes strictly specialized in egg production. We demonstrate that the presence of workers is necessary and sufficient to induce this specialization of queens. Moreover, workers also maintain the queen specialization in mature colonies, as established queens isolated from their workers revert to expressing behavioral pluripotency. Our results also suggest that this underappreciated social control of queen specialization may be common in ants and regulated by ancestral mechanisms. These findings stand in contrast to the traditional view of social insect queens as being intrinsically specialized in egg production and may reshape our understanding of division of labor in insect societies.Significance statementInsect societies are characterized by division of labor between queens that specialize in producing eggs and workers that perform all non-reproductive tasks. Studies of division of labor traditionally focused on fully established colonies and there is limited information on the factors and mechanisms that initiate division of labor during colony foundation. Here, we report that the presence of workers not only initiates the queen specialization, but also maintains it continually throughout the colony life. Finding such a social control of the specialization of queens contradicts the commonly accepted view of social insect queens as intrinsically specialized egg-laying machines. Our study has the potential to reshape our understanding of the functioning and evolution of insect societies.
Complete identity of the cis-asRNA StfZ and its influence on FtsZ protein level and cell division in Escherichia coli
Authors: Anand Deepak , Jakkala Kishor , Nair Rashmi Ravindran , Sharan Deepti , Pradhan Atul , Mukkayyan Nagaraja , Ajitkumar Parthasarathi 
Published: March 2022

AbstractBacteria regulate FtsZ protein levels through transcriptional and translational mechanisms for proper cell division. A cis-antisense RNA, StfZ, produced from the ftsA-ftsZ intergenic region was proposed to regulate the FtsZ level in Escherichia coli. However, its structural identity remained unknown. In the present study, we determined the complete sequence, identified the promoters, and effects of StfZ on the FtsZ level. We show that StfZ is expressed at 1:6 ratio of StfZ:ftsZ mRNA at all growth phases from three promoters as three isoforms of 366 nt, 474 nt, and 552 nt. Overexpression of StfZ reduces FtsZ level, increases cell size, and blocks cell division. Thus, the cis-encoded StfZ emerges as a novel factor for maintaining the FtsZ level at different growth phases in E. coli.
AlphaFold2 fails to predict protein fold switching
Authors: Chakravarty Devlina , Porter Lauren L. 
Published: March 2022

AbstractAlphaFold2 has revolutionized protein structure prediction by leveraging sequence information to rapidly model protein folds with atomic-level accuracy. Nevertheless, previous work has shown that these predictions tend to be inaccurate for structurally heterogeneous proteins. To systematically assess factors that contribute to this inaccuracy, we tested AlphaFold2’s performance on 98 fold-switching proteins, which assume at least two distinct-yet-stable secondary and tertiary structures. Topological similarities were quantified between five predicted and two experimentally determined structures of each fold-switching protein. Overall, 94% of AlphaFold2 predictions captured one experimentally determined conformation but not the other. Despite these biased results, AlphaFold2’s estimated confidences were moderate-to-high for 74% of fold-switching residues, a result that contrasts with overall low confidences for intrinsically disordered proteins, which are also structurally heterogeneous. To investigate factors contributing to this disparity, we quantified sequence variation within the multiple sequence alignments used to generate AlphaFold2’s predictions of fold-switching and intrinsically disordered proteins. Unlike intrinsically disordered regions, whose sequence alignments show low conservation, fold-switching regions had conservation rates statistically similar to canonical single-fold proteins. Furthermore, intrinsically disordered regions had systematically lower prediction confidences than either fold-switching or single-fold proteins, regardless of sequence conservation. AlphaFold2’s high prediction confidences for one fold-switching conformation corroborate previous work showing that machine-learning-based structure predictors fail to capture other fundamental biophysical features of proteins such as their folding pathways. Our results emphasize the need to look at protein structure as an ensemble and suggest that systematic examination of fold-switching sequences may reveal propensities for multiple stable secondary and tertiary structures.
Efficacy of plasmid-encoded CRISPR-Cas antimicrobial is affected by competitive factors found in wildEnterococcus faecalisisolates
Authors: Araya Dennise Palacios , Islam Moutusee , Moni Shah O. , Ramjee Christine A. , Ngo Tuong-Vi Cindy , Palmer Kelli L. 
Published: March 2022

ABSTRACTEnterococcus faecalisis a leading cause of hospital-acquired infections. These infections are becoming more difficult to treat due to the increasing emergence ofE. faecalisstrains resistant to last resort antibiotics. Over the past decade, multiple groups have engineered the naturally occurring bacterial defense system CRISPR-Cas as a sequence-specific antimicrobial to combat antibiotic-resistant bacteria. We have previously established that the type II CRISPR-Cas system ofE. faecaliscan be reprogrammed as a CRISPR-Cas antimicrobial and delivered to antibiotic-resistant recipients on a conjugative pheromone-responsive plasmid. Using a co-culture system, we showed sequence-specific depletion of antibiotic resistance fromE. faecalismodel strains, bothin vitroandin vivo. Although this and other studies have demonstrated the potential use for CRISPR-Cas as an antimicrobial, most have deployed the system against model bacterial strains. Thus, there is limited knowledge on how effective these potential therapies are against recently isolated and uncharacterized strains with limited laboratory passage, which we refer to here as wild strains. Here, we compare the efficacy of our previously established CRISPR-Cas antimicrobials against bothE. faecalismodel strains and wildE. faecalisfecal isolates. We demonstrate that these wild isolates can antagonize the CRISPR-Cas antimicrobial donor strain via competitive factors like cytolysin. Furthermore, we show that the wild isolates can effectively prevent delivery of the CRISPR-Cas antimicrobial plasmids, consequently avoiding CRISPR-Cas targeting. Our results emphasize the requisite to study CRISPR-Cas antimicrobials against wild strains to understand limitations and develop delivery systems that can endure competitive interspecies interactions in the gut microenvironment and effectively deliver CRISPR-Cas antimicrobials to their intended targets.IMPORTANCEEnterococcus faecalisis a major nosocomial pathogen. Traditional antibiotics continue to lose potency against these opportunistic pathogens as they become increasingly resistant to more antibiotics. We previously showed that our CRISPR-Cas antimicrobials can deplete drug resistance in or killE. faecalismodel strains. Here, we examined the efficacy of CRISPR-Cas antimicrobials against a recent collection ofE. faecalisfecal isolates. We found that CRISPR-Cas delivery and efficacy is affected by competitive factors produced by the wild isolates. Our study emphasizes the need to study CRISPR-Cas antimicrobials in the context of wild bacterial isolates, which are the intended target for this potential therapy, in order to understand limitations and develop CRISPR-enhanced antimicrobials with effective clinical applications.
Mitochondrial Transcription Factor A Regulates Foxp3+ T Cell Mediated Maintenance of CD4+ T Cell Landscapes and Immunological Aging
Authors: Guo Kai , Wang Zhihan , Debnath Trishna , Mehta Het , Abrham Eden , Even Zachery , Rahman Mansib , Da Costa Abby Lund , Jain Shilpi , Wang Xusheng , Hur Junguk , Murugaiyan Gopal , Ting Adrian T. , Brown-Borg Holly , Jurivich Donald A , Khan Nadeem , Mathur Ramkumar 
Published: March 2022

AbstractA decline in mitochondrial activity has been linked to T cell dysfunction and the progression of a variety of diseases. It is unclear whether the mitochondrial function in regulatory T cells (Tregs) determines effector T cell fate decisions and regulates steady-state inflammation. We show that loss of Mitochondrial Transcription Factor A in Foxp3+ Tregs (TFAM cKO) affects the cellular and transcriptional dynamics of CD4+ T cells, resulting in disproportional cellular heterogeneity and prevalence of pathogenic CD4+ T cell subsets. Failure to modulate CD4+ T cell responses results in systemic inflammation, immunological aging, and shortened lifespans in TFAM cKO mice. Furthermore, we found that TFAM heterozygous (Het) mice with 50% allelic restoration had a progressive decrease in physiological, cognitive, and neuromuscular activity starting at 8 months, implying that the TFAM Het mouse model has the potential to be used for in-depth research on age-related inflammatory diseases. Overall, TFAM depletion in Tregs explains the steady-state reduction in Treg function with age. TFAM restoration in Tregs could be a target for preserving the homeostatic CD4+ T cell pool and avoiding cognitive impairments caused by inflammation induced aging (inflammaging).
A spatio-temporally constrained gene regulatory network directed by PBX1/2 acquires limb patterning specificity via HAND2
Authors: Losa Marta , Barozzi Iros , Osterwalder Marco , Zarrineh Peyman , Benazet Jean Denis , Chacon Brandon , Girdziusaite Ausra , Morabito Angela , Zhu Jianjian , Mackem Susan , Capellini Terence D. , Bobola Nicoletta , Dickel Diane , Zuniga Aimee , Visel Axel , Zeller Rolf , Selleri Licia 
Published: March 2022

ABSTRACTDuring development cell fates are specified by tightly controlled gene expression programs. PBX TALE transcription factors control gene regulatory networks (GRN) that direct vertebrate tissue patterning and organ morphogenesis. How PBX1/2 proteins acquire context-specific functions, despite widespread embryonic expression of Pbx1/2, remains elusive. In mouse limb buds, mesenchymal-specific loss of PBX1/2 or of the transcriptional regulator HAND2 results in similar phenotypes, suggesting that PBX1/2- and HAND2-dependent programs converge to control limb development. To investigate this scenario, we combined tissue-specific and temporally-controlled mutagenesis with multi-omics approaches using the murine hindlimb bud as a model. We reconstructed a GRN collaboratively directed by PBX1/2 and HAND2, demonstrating that Pbx1-Hand2 genetically interact in vivo during hindlimb patterning, with PBX1 concomitantly acting as an upstream regulator of Hand2. At organismal-level resolution the GRN is active within restricted subsets of posterior-proximal hindlimb mesenchymal cells, wherein Pbx1/2 and Hand2 are co-expressed with their target genes. Genome-wide profiling of PBX1 binding across multiple tissues further revealed that HAND2 selects a subset of PBX-bound regions to impart limb patterning functionality. This research elucidates mechanisms underlying limb bud-specific functions by PBX1/2, while informing general principles by which promiscuous transcription factors cooperate with select cofactors to instruct distinct developmental programs.
A happy accident: a novel turfgrass reference genome
Authors: Phillips Alyssa R. , Seetharam Arun S. , Albert Patrice S. , AuBuchon-Elder Taylor , Birchler James A. , Buckler Edward S. , Gillespie Lynn J. , Hufford Matthew B. , Llaca Victor , Romay M. Cinta , Soreng Robert J. , Kellogg Elizabeth A. , Ross-Ibarra Jeffrey 
Published: March 2022

ABSTRACTPoa pratensis, commonly known as Kentucky bluegrass, is a popular cool-season grass species used as turf in lawns and recreation areas globally. Despite its substantial economic value, a reference genome had not previously been assembled due to the genome’s relatively large size and biological complexity that includes apomixis, polyploidy, and interspecific hybridization. We report here a fortuitousde novoassembly and annotation of aP. pratensisgenome. Instead of sequencing the genome of a C4 grass, we accidentally sampled and sequenced tissue from a weedyP. pratensiswhose stolon was intertwined with that of the C4 grass. The draft assembly consists of 6.09 Gbp with an N50 scaffold length of 65.1 Mbp, and a total of 118 scaffolds, generated using PacBio long reads and Bionano optical map technology. We annotated 256K gene models and found 58% of the genome to be composed of transposable elements. To demonstrate the applicability of the reference genome, we evaluated population structure and estimated genetic diversity inP. pratensiscollected from three North American prairies, two in Manitoba, Canada and one in Colorado, USA. Our results support previous studies that found high genetic diversity and population structure within the species. The reference genome and annotation will be an important resource for turfgrass breeding and study of bluegrasses.
Practical implications of Lean, Six Sigma and Lean Six Sigma in the public administration sector: a systematic literature review
Authors: Psomas Evangelos , Keramida Efthalia , Bouranta Nancy 
Published: March 2022

Purpose
The purpose of this study is to identify the practical implications of Lean, Six Sigma (SS) and Lean SS (LSS) in the public administration sector. Determining the key themes of these practical implications is also an aim of the present study.

Design/methodology/approach
A systematic literature review (SLR) was conducted based on the databases of six well-known academic publishers, namely, Emerald, Elsevier/Science Direct, Springer Link, Taylor and Francis, Sage and Willey online. The review revealed 56 peer-reviewed journal articles published between 2004 and 2020. The “affinity diagram” was applied to group the practical implications of Lean, SS and LSS into logical themes.

Findings
A plethora of practical implications of Lean, SS and LSS in the public administration sector are identified in the literature, examples of which are analytically presented. The analysis showed that the practical implications identified can be grouped into 14 meaningful themes, and these themes in turn into categories, formulating thus, a conceptual framework. The key themes that are supported in the literature by most references are the following: human factors involved in Lean/SS/LSS, Lean/SS/LSS benefits and Lean/SS/LSS implementation issues.

Research limitations/implications
Although several databases were used, some publishers might have been missed out in this SLR. The subjectivity in applying the “affinity diagram” is also a limitation of this study. Based on these limitations, further literature review studies can be designed.

Practical implications
Twofold implications arise from the present study, meaning from the practitioner and the academic perspective. The practical implications identified as well as their meaningful themes revealed constitute useful guidelines for managers and decision-makers wishing to implement Lean/SS/LSS in the public administration sector and bridge their knowledge gap between theory and practice. Moreover, all the practical dimensions of Lean/SS/LSS included in the comprehensive conceptual framework formulated could serve as research avenues for academics.

Originality/value
The application of Lean/SS/LSS in the public sector has not been widely reviewed, while the stream of literature focuses on limited issues (critical success factors, benefits, challenges, etc.). Moreover, SLRs in services and specifically in the public administration sector are fewer. Stimulated by this gap and the suggestions of other researchers for future studies, to the best of the authors’ knowledge, this study provides the first SLR which analyzes the practical implications of Lean/SS/LSS in the public administration sector and determines their key themes.
Modeling of a wheeled humanoid robot and hybrid algorithm-based path planning of wheel base for the dynamic obstacles avoidance
Authors: Sulaiman Shifa , Sudheer A.P. 
Published: March 2022

Purpose
Most of the conventional humanoid modeling approaches are not successful in coupling different branches of the tree-type humanoid robot. In this paper, a tree-type upper body humanoid robot with mobile base is modeled. The main purpose of this work is to model a non holonomic mobile platform and to develop a hybrid algorithm for avoiding dynamic obstacles. Decoupled Natural Orthogonal Complement methodology effectively combines different branches of the humanoid body during dynamic analysis. Collision avoidance also plays an important role along with modeling methods for successful operation of the upper body wheeled humanoid robot during real-time operations. The majority of path planning algorithms is facing problems in avoiding dynamic obstacles during real-time operations. Hence, a multi-fusion approach using a hybrid algorithm for avoiding dynamic obstacles in real time is introduced.

Design/methodology/approach
The kinematic and dynamic modeling of a humanoid robot with mobile platform is done using screw theory approach and Newton–Euler formulations, respectively. Dynamic obstacle avoidance using a novel hybrid algorithm is carried out and implemented in real time. D star lite and a geometric-based hybrid algorithms are combined to generate the optimized path for avoiding the dynamic obstacles. A weighting factor is added to the D star lite variant to optimize the basic version of D star lite algorithm. Lazy probabilistic road map (PRM) technique is used for creating nodes in configuration space. The dynamic obstacle avoidance is experimentally validated to achieve the optimum path.

Findings
The path obtained using the hybrid algorithm for avoiding dynamic obstacles is optimum. Path length, computational time, number of expanded nodes are analysed for determining the optimality of the path. The weighting function introduced along with the D star lite algorithm decreases computational time by decreasing the number of expanding nodes during path generation. Lazy evaluation technique followed in Lazy PRM algorithm reduces computational time for generating nodes and local paths.

Originality/value
Modeling of a tree-type humanoid robot along with the mobile platform is combinedly developed for the determination of the kinematic and dynamic equations. This paper also aims to develop a novel hybrid algorithm for avoiding collision with dynamic obstacles with minimal computational effort in real-time operations.