bluuebunny/crossref_metadata_2025 huggingface dataset:
On-Farm Genetic Diversity of Wheat (Triticum aestivum spp.) In Digalu Tijo District, Arsi Zone, Ethiopia
Authors: Gelelcha Fekadu , Kumsa Fikadu , Kuma Tolera
Published: March 2022

Introductory

This study was undertaken to assess the on-farm genetic diversity of wheat Landraces (Triticum aestivum spp) in Digalu and Tijo District.

Methods

For this study, three farmer households kebeles were selected by cluster sampling (area sampling) method because they are found in the most dominant wheat landraces growing agro-ecological areas. Data for this study was collected using questionnaires, field observation, interviews, focus group discussion, and document analysis.

Results and Discussions

In total, 27 wheat landraces were reported to be grown before two decades to the present day. Of these, only 9 of wheat landraces are still cultivated by farmers. Among these, ‘Qamadi guracha’ is the most common growing landraces in the study area. The Shannon diversity index (H’) of growing wheat landraces ranges from 1.09 to 1.37 among the groups. The estimated genetic erosion for wheat landraces was found to be 66.7% due to the major factors: improved wheat varieties; the introduction of other more productive crops and wheat landraces low productivity.

Conclusions

Food quality, Pests (example, birds), diseases resistance, market value, and straw quality were factors that initiated the farmers to maintain the genetic diversity of landraces on their farmlands. However, the preservation of wheat landraces are influenced by bottlenecks like the seed selection system, and insufficient crop yield.

Recommendation

Regeneration of soil fertility, restoring of lost landraces, improvement of landraces, on-farm conservation by re-sowing, saving of seeds for future, and ex-situ conservation is suggested for the restoration of wheat landraces diversity in Digalu and Tijo District.
ImputAccur: fast and user-friendly calculation of genotype-imputation accuracy-measures
Authors: Thormann Kolja A , Tozzi Viola , Starke Paula , Bickeböller Heike , Baum Marcus , Rosenberger Albert
Published: March 2022

ImputAccur is a software tool for genotype-imputation accuracy-measures. Imputation of untyped markers is a standard approach in genome-wide association studies to close the gap between directly genotyped and other known DNA variants. However high accuracy for imputed genotypes is fundamental. Several accuracy measures have been proposed, but unfortunately, they are implemented on different platforms, which is impractical. With ImputAccur the accuracy measures info, Iam-hiQ and r²based indices can be derived from standard output-files of imputation software. Sample/probe and marker filtering is possible. This allows e.g. accurate marker filtering ahead of data analysis. A Python code is available but also a stand-alone executable file.

Availability and Implementation

The source code (Python version 3.9.4), a stand-alone executive file, and example data for ImputAccur are freely available at https://gitlab.gwdg.de/kolja.thormann1/imputationquality.git.

Supplementary Information

Supplementary information is available at Bioinformatics online.

Contact

arosenb@gwdg.de or koljaalexander.thormann@uni-goettingen.de
Reconstitution of Kinetochore and Microtubule Dynamics Reveals a Role for a Kinesin-8 in Establishing End-on Attachments
Authors: Torvi Julia R. , Wong Jonathan , Serwas Daniel , Moayed Amir , Drubin David G. , Barnes Georjana
Published: March 2022

During mitosis, individual microtubules make attachments to chromosomes via a specialized protein complex called the kinetochore to faithfully segregate the chromosomes to daughter cells. Translocation of kinetochores on the lateral surface of the microtubule has been proposed to contribute to high fidelity chromosome capture and alignment at the mitotic midzone, but has been difficult to observe in vivo because of spatial and temporal constraints. To overcome these barriers, we used total internal reflection fluorescence (TIRF) microscopy to track the interactions between endogenously tagged tubulin, kinetochore proteins, and other microtubule-associated proteins in lysates from metaphase-arrested Saccharomyces cerevisiae. Using both TIRF microscopy and cryo-correlative light microscopy and electron tomography, we successfully reconstituted microtubule-bound, intact kinetochores. These kinetochores translocate on the lateral microtubule surface toward the microtubule plus end and transition to end-on attachment, whereupon microtubule depolymerization commences. The directional kinetochore movement is dependent on the highly processive kinesin-8, Kip3. We propose that Kip3 facilitates stable kinetochore attachment to microtubule plus ends through its abilities to move the kinetochore laterally on the surface of the microtubule and to regulate microtubule plus end dynamics.
RUNX1 isoform disequilibrium in the development of trisomy 21 associated myeloid leukemia
Authors: Gialesaki Sofia , Bräuer-Hartmann Daniela , Bhayadia Raj , Alejo-Valle Oriol , Issa Hasan , Regenyi Enikő , Beyer Christoph , Labuhn Maurice , Ihling Christian , Sinz Andrea , Glaß Markus , Hüttelmaier Stefan , Matzk Sören , Schmid Lena , Strüwe Farina Josepha , Kadel Sofie-Katrin , Reinhardt Dirk , Yaspo Marie-Laure , Heckl Dirk , Klusmann Jan-Henning
Published: March 2022

Aneuploidy is a hallmark of cancer, but its complex nature limits our understanding of how it drives oncogenesis. Gain of chromosome 21 (Hsa21) is among the most frequent aneuploidies in leukemia and is associated with markedly increased leukemia risk. Here, we propose that disequilibrium of the RUNX1 isoforms is key to the pathogenesis of trisomy 21 (i.e. Down syndrome)-associated myeloid leukemia (ML-DS). Hsa21-focused CRISPR-Cas9 screens uncovered a strong and specific RUNX1 dependency in ML-DS. Mechanistic studies revealed that excess of RUNX1A isoform – as seen in ML-DS patients – synergized with the pathognomonic Gata1s mutation in leukemogenesis by displacing RUNX1C from its endogenous binding sites and inducing oncogenic programs in complex with the MYC cofactor MAX. These effects were reversed by restoring the RUNX1A:RUNX1C equilibrium or pharmacological interference with MYC:MAX dimerization. Our study highlights the importance of alternative splicing in leukemogenesis, even on a background of aneuploidies, and opens new avenues for developing specific and targeted therapies.

Graphical Abstract
Effects of chronic cannabidiol in a mouse model of naturally occurring neuroinflammation, neurodegeneration, and spontaneous seizures
Authors: Dearborn Joshua T. , Nelvagal Hemanth R. , Rensing Nicholas R. , Hughes Stephanie M. , Wishart Thomas M , Cooper Jonathan D. , Wong Michael , Sands Mark S.
Published: March 2022

Cannabidiol (CBD) has gained attention as a therapeutic agent and is purported to have immunomodulatory, neuroprotective, and anti-seizure effects. Here, we determined the effects of chronic CBD administration in a mouse model of CLN1 disease (Cln1-/-) that simultaneously exhibits neuroinflammation, neurodegeneration, and spontaneous seizures. Proteomic analysis showed that putative CBD receptors are expressed at similar levels in the brains ofCln1-/-mice compared to normal animals.Cln1-/-mice received an oral dose (100mg/kg/day) of CBD for six months and were evaluated for changes in pathological markers of disease and seizures. Chronic cannabidiol administration was well-tolerated, high levels of CBD were detected in the brain, and markers of astrocytosis and microgliosis were reduced. However, CBD had no apparent effect on seizure frequency or neuron survival. These data are consistent with CBD having immunomodulatory effects. It is possible that a higher dose of CBD could also reduce neurodegeneration and seizure frequency.
Extensive neutralization against SARS-CoV-2 variants elicited by Omicron-specific subunit vaccine booster
Authors: Peng Pai , Feng Chengqian , Hu Jie , He Chang-long , Deng Hai-jun , Fan Qinghong , Xiang Jin , Tang Guofang , Jiang Mengling , Hu Fengyu , Li Feng , Wang Kai , Tang Ni , Tang Xiaoping , Huang Ai-long
Published: March 2022

The currently dominant variant of SARS-CoV-2 Omicron, carrying a great number of mutations, has been verified its strong capacity of immune escape in COVID-19 convalescents and vaccinated individuals. An increased risk of SARS-CoV-2 reinfection or breakthrough infection should be concerned. Here we reported higher humoral immune response elicited by Delta and Omicron variants after breaking through previous infection and cross-neutralization against VOCs, compared to the ancestral wild-type (WT) virus infection. To overcome the immune escape of Omicron, Omicron-specific vaccine was considered as a novel and potential strategy. Mouse models were used to verify whether Omicron-specific RBD subunit boost immune response by immunizing Omicron-RBD recombinant proteins. Three doses of Omicron-RBD immunization elicit comparable neutralizing antibody (NAb) titers with three doses of WT-RBD immunization, but the neutralizing activity was not cross-active. By contrast, two doses of WT-RBD with an Omicron-RBD booster increased the NAb geometric mean titers against Omicron by 9 folds. Moreover, an additional boost vaccination with Omicron-RBD protein could increase humoral immune response against both WT and current VOCs. These results suggest that the Omicron-specific subunit booster shows its advantages in the immune protection from both WT and current VOCs, and that SARS-CoV-2 vaccines administration using two or more virus lineages as antigens might improve the NAb response.
The importance of environmental parameters and mixing zone in shaping estuarine microbial communities along a freshwater-marine gradient
Authors: Da Silva R.R.P. , White C.A. , Bowman J.P. , Bodrossy L. , Bissett A. , Revill A. , Eriksen R. , Ross D.J.
Published: March 2022

Microbial communities are important elements in the marine environment, contributing to nutrient cycling and biogeochemical processes. Estuaries comprise environments exhibiting characteristics from freshwater to marine, leading to distinct microbial communities across this environmental gradient. Here, we examine the spatial dynamics of microbial communities in Macquarie Harbour, an estuarine system on the West coast of Tasmania, Australia. Water was sampled along the estuary to explore the structure and composition of the microbial communities using 16S/18S rRNA gene amplicon sequencing. Multivariate analyses showed environmental variables and community compositions varying along a longitudinal (river to adjacent ocean) gradient at the surface. In the harbour, differences in the microbial community were observed between surface (0-1 m) and intermediate depths (4.5-11 m depth). The results of differential abundance, network and Partial Least Square analyses suggest that Macquarie Harbour is a mixing zone, where the distributions of archaeal, bacterial and eukaryotic communities are influenced by oceanic and riverine inputs. Coupled with the natural characteristics of the Harbour, the heterotrophic component of this microbial communities inhabiting the surface and intermediate waters may play important roles in the nutrient cycle in the studied area. These results provide critical insights into the Macquarie Harbour environment and the importance of understanding the role of microbial communities for similar systems elsewhere.
In situ architecture of the lipid transport protein VPS13C at ER-lysosomes membrane contacts
Authors: Cai Shujun , Wu Yumei , Guillen-Samander Andres , Hancock-Cerutti William , Liu Jun , De Camilli Pietro
Published: March 2022

VPS13 is a eukaryotic lipid transport protein localized at membrane contact sites. Previous studies suggested that it may transfer lipids between adjacent bilayers by a bridge-like mechanism. Direct evidence for this hypothesis from a full-length structure and from EM studies in situ, however, is still missing. Here we have capitalized on AlphaFold predictions to complement the structural information already available about VPS13 and to generate a full-length model of human VPS13C, the Parkinson’s disease-linked VPS13 paralog localized at contacts between the ER and endo/lysosomes. Such model predicts a ~30-nm rod with a hydrophobic groove that extends throughout its length. We further investigated whether such a structure can be observed in situ at ER-endo/lysosome contacts. To this aim, we combined genetic approaches with cryo-focused-ion-beam (cryo-FIB) milling and cryo-electron tomography (cryo-ET) to examine HeLa cells overexpressing this protein (either full length or with an internal truncation) along with VAP, its anchoring binding partner at the ER. Using these methods we identified rod-like densities that span the space separating the two adjacent membranes and that match the predicted structures of either full length VPS13C or its shorter truncated mutant, thus providing the first in-situ evidence for a bridge-model of VPS13 in lipid transport. Intriguingly, the majority of the VPS13C rods were separated from the ER membranes by a narrow gap, suggesting that while VAP anchors the protein to the ER, direct contact of the VPS13C rod with the ER bilayer to allow lipid transport may be independently regulated.
CD47-SIRPα controls ADCC killing of primary T cells by PMN through a combination of trogocytosis and NADPH oxidase activation
Authors: Gondois-Rey Françoise , Miller Thomas W. , Nunès Jacques A. , Olive Daniel
Published: March 2022

Immunotherapies targeting the “don’t eat me” myeloid checkpoint constituted by CD47 SIRPα interaction have promising clinical potential but are limited by toxicities associated with the destruction of non-tumor cells. These dose-limiting toxicities demonstrate the need to highlight the mechanisms of anti-CD47-SIRPα therapy effects on non-tumor CD47-bearing cells. Given the increased incidence of lymphopenia in patients receiving anti-CD47 antibodies, and the strong ADCC effector function of Poly Morpho Nuclear Cells (PMNs), we investigated the behavior of primary PMNs cocultured with primary T cells in the presence of anti-CD47 mAbs. PMNs killed T cells in a CD47-mAb-dependent manner and at a remarkably potent PMN to T cell ratio of 1:1. The observed cytotoxicity was produced by a novel combination of both trogocytosis and a strong respiratory burst induced by classical ADCC and CD47-SIRPα checkpoint blockade. The complex effect of the CD47 blocking mAb could be recapitulated by combining its individual mechanistic elements: ADCC, SIRPα blockade and ROS induction. Although previous studies had concluded that disruption of SIRPα signaling in PMNs was limited to trogocytosis-specific cytotoxicity, our results suggest that SIRPα also tightly controls activation of NADPH oxidase, a function demonstrated during differentiation of immature PMNs but not so far in mature PMNs. Together, our results highlight the need to integrate PMNs in the development of molecules targeting the CD47-SIRPα immune checkpoint and to design agents able to enhance myeloid cells function while limiting adverse effects to healthy cells able to participate in the anti-tumor immune response.

Synopsis

Dose-limiting toxicities demonstrate the need to investigate anti-CD47-SIRPα therapy effects on non-tumor CD47-bearing cells. We demonstrate that anti-CD47 mAbs stimulate potent killing of T cells by PMN through a novel combination of trogocytosis and ROS regulated by SIRPα.

Graphical Abstract
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

Lissencephaly-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

Tears 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

A 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 statement

Insect 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

Bacteria 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

AlphaFold2 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

Enterococcus 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.

IMPORTANCE

Enterococcus 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

A 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

During 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

Poa 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.
Responsibility, stress and the well-being of school principals: how principals engaged in self-care during the COVID-19 crisis
Authors: Hayes Sonya D. , Anderson Erin , Carpenter Bradley W.
Published: March 2022

Purpose

This study centers the reflections of principals across the USA as they navigated the overwhelming stress of closing and reopening schools during a global pandemic. Specifically, the authors explored how school principals addressed self-care and their own well-being during the pandemic.

Design/methodology/approach

This research study is part of a broader qualitative study conducted by 20 scholars from across the USA in Spring 2020 and organized by the Consortium for Policy Research in Education (CPRE). This national research team conducted 120 qualitative interviews with public school principals in 19 different states and 100 districts. As part of this team, the authors coded and analyzed all 120 transcripts in NVivo using a self-care framework.

Findings

The responses from the participants capture some of the complexity of self-care during the COVID-19 pandemic. The authors found evidence of both negative and positive sentiments towards self-care that will be described in five major themes. For the tensions with self-care, the authors developed two primary themes: leaders eat last and keep from falling off the cliff. For the demonstrations of self-care, the authors also developed three primary themes: release the endorphins, people need people and unplug from work.

Originality/value

Although researchers have identified the stressors and reactions of principals during the early months of the COVID-19 pandemic, little is known on how principals engaged in self-care practices. This study aims to identify these self-care practices and offer recommendations for principals.
Determinants of public–private partnerships: an empirical analysis of Asia
Authors: Malik Sakshi , Kaur Simrit
Published: March 2022

Purpose

Despite being a global public–private partnerships (PPPs) leader, the Asian region is characterised by a wide PPP-divide, wherein select countries attract majority of PPP projects, while other countries fail to attract the requisite PPP investments. Against this background, the purpose of this study is to investigate the determinants of PPP projects in Asia.

Design/methodology/approach

Using quantitative methods on secondary data, this study analyses the macroeconomic determinants of value and number of PPPs in Asia for the period 2010–2019. The methodology relies on panel fixed effects, random effects, two-step system generalised method of moments and negative binomial regression.

Findings

Results underline the importance of the country’s experience with PPPs, physical infrastructure, financial sector development, market conditions, institutional quality and political stability in attracting PPP projects.

Practical implications

Identification of the determinants of PPPs will assist private investors in making informed decisions related to the selection of countries for PPP investments, thereby increasing the likelihood of a project’s success.

Social implications

The results are expected to enable countries to formulate policies aimed at attracting higher PPP investments, thereby propelling economic development and improvement in the quality of life.

Originality/value

To the best of the authors’ knowledge, this is the first such study that comprehensively analyses the determinants of both value of PPP investments and number of PPP projects for Asian countries.
Uniting the scales of microbial biogeochemistry with trait‐based modelling
Authors: Wan Joe , Crowther Thomas W.
Published: March 2022

Below‐ground microbial communities drive some of Earth's largest biogeochemical fluxes, yet they represent a major source of uncertainty in global biogeochemical models. This review synthesizes recent advances in trait‐based soil carbon modelling in order to identify how empirical observations of microbial traits can inform the next generation of soil carbon models.

We identify four key perspectives from which trait‐based models have investigated the role of microbes in soil carbon fluxes, ranging from the largest to the smallest scales of biological organization: (i) Earth system models, which have recently begun to incorporate microbial traits at a global scale; (ii) ecosystem models, which relate microbial carbon cycling to other trophic levels and element cycles; (iii) models from community ecology, which link theories of species diversity to ecosystem cycles; and (iv) models of fine‐scale physiology, which mechanistically represent traits at the individual level.

Highlighting the contributions of diverse trait‐based modelling approaches, we caution that this diversity makes it challenging to link perspectives at different scales. The meaning of a trait depends both on the structure of the model in which it occurs and on the scale treated by the model. Thus, reapplying a fine‐scale trait at a broader scale may make incorrect predictions, an issue we illustrate quantitatively using model simulations.

With these challenges in mind, we highlight several ways to synthesize the scales of microbial biogeochemical modelling: (i) quantitatively, using mathematical scaling techniques, (ii) empirically, by applying experiments to test relationships between scales and (iii) conceptually, by identifying key traits and processes across scales.

Taking full advantage of trait‐based modelling, ecologists will thus be able to incorporate multiple perspectives to better predict carbon cycling in a changing world.

Read the free Plain Language Summary for this article on the Journal blog.
Ant body size mediates functional performance and species interactions in carrion decomposer communities
Authors: Nooten Sabine S. , Chan Kin H. , Schultheiss Patrick , Bogar Taylor A. , Guénard Benoit
Published: March 2022

Growing concern over rapid species declines and extinctions has led to considerable interest in the role of biodiversity for maintaining ecological processes. However, the loss of particular species has more pronounced effects on ecosystem services than others, highlighting the importance of key functional species traits and their relationships to ecosystem functioning. Human‐induced disturbances, such as species invasions, land use changes, or abiotic changes, appear to disproportionally impact larger species rather than smaller ones. The loss of large‐bodied species in the community diminishes key ecosystem services like seed dispersal, pest control, pollination and decomposition.

Here, we use carrion, a nutrient‐rich ephemeral resource, to test the hypotheses that ants positively affect decomposition rates and that their role in the necrophilous community—as predator or decomposer—is mediated by body size. We further investigate the relative contribution of maggots versus ants to biomass decomposition.

Our results show that ants contributed positively to the decomposition process. Moreover, decomposition was shaped by an intricate interplay between competition and predation among the guild of decomposer insects. As predicted, larger ants show a double action in increasing decomposition rate and predating on maggots, while small ants are rather inefficient decomposers and did not act as predators on other decomposer species.

Our study shows that differentiating key taxonomic groups in function of their body size is key to untangle the diversity and directions of the various roles they play within complex ecological processes.

Read the free Plain Language Summary for this article on the Journal blog.
Complex community‐wide consequences of consumer sexual dimorphism
Authors: De Lisle Stephen P. , Schrieber Sebastian J. , Bolnick Daniel I.
Published: March 2022

Sexual dimorphism is a ubiquitous source of within‐species variation, yet the community‐level consequences of sex differences remain poorly understood.

Here, we analyse a bitrophic model of two competing resource species and a sexually reproducing consumer species.

We show that consumer sex differences in resource acquisition can have striking consequences for consumer‐resource coexistence, abundance and dynamics.

Under both direct interspecific competition and apparent competition between two resource species, sexual dimorphism in consumers' attack rates can mediate coexistence of the resource species, while in other cases can lead to exclusion when stable coexistence is typically expected. Slight sex differences in total resource acquisition also can reverse competitive outcomes and lead to density cycles. These effects are expected whenever both consumer sexes require different amounts or types of resources to reproduce.

Our results suggest that consumer sexual dimorphism, which is common, has wide‐reaching implications for the assembly and dynamics of natural communities.
Are stress‐related pathways of social status differentiation more important determinants of health inequities in countries with higher levels of income inequality?
Authors: Olstad Dana Lee , Nejatinamini Sara , Vanderlee Lana , Livingstone Katherine M. , Campbell David J. T. , Tang Karen , Minaker Leia M. , Hammond David
Published: March 2022

We explored socioeconomic gradients in self‐rated overall health (SROH) using indicators of materialist (educational attainment and perceived income adequacy) and psychosocial perspectives (subjective social status (SSS)) among adults living in countries with varying levels of income inequality, and the importance of psychosocial stress in mediating these associations. If psychosocial processes at the individual and societal levels correspond, associations between SSS and SROH should be higher among adults in countries with higher income inequality, and psychosocial stress should be a more important mediator of these associations. We used multigroup structural equation models to analyse cross‐sectional data from the International Food Policy Study of adults (n = 22,824) in Australia, Canada, Mexico, the UK and the United States. Associations between SSS and SROH were not higher in more unequal countries, nor was psychosocial stress a more important mediator of these associations. Inequities in SROH in more unequal countries may not predominantly reflect stress‐related pathways of social status differentiation.