bluuebunny/crossref_metadata_2025 huggingface dataset:
In-depth phylogenomic analysis of arbuscular mycorrhizal fungi based on a comprehensive set of de novo genome assemblies
Authors: Montoliu-Nerin Merce , Sánchez-García Marisol , Bergin Claudia , Kutschera Verena Esther , Johannesson Hanna , Bever James D. , Rosling Anna
Published: April 2021

Morphological characters and nuclear ribosomal DNA (rDNA) phylogenies have so far been the basis of the current classifications of arbuscular mycorrhizal (AM) fungi. Improved understanding of the phylogeny and evolutionary history of AM fungi requires extensive ortholog sampling and analyses of genome and transcriptome data from a wide range of taxa.

To circumvent the need for axenic culturing of AM fungi we gathered and combined genomic data from single nuclei to generatede novogenome assemblies covering seven families of AM fungi. Comparative analysis of the previously publishedRhizophagus irregularisDAOM197198 assembly confirm that our novel workflow generates high-quality genome assemblies suitable for phylogenomic analysis. Predicted genes of our assemblies, together with published protein sequences of AM fungi and their sister clades, were used for phylogenomic analyses.

Based on analyses of sets of orthologous genes, we highlight three alternative topologies among families of AM fungi. In the main topology, Glomerales is polyphyletic and Claroideoglomeraceae, is the basal sister group to Glomeraceae and Diversisporales.

Our results support family level classification from previous phylogenetic studies. New evolutionary relationships among families where highlighted with phylogenomic analysis using the hitherto most extensive taxon sampling for AM fungi.
Motor usage imprints microtubule stability in the shaft
Authors: Andreu-Carbó Mireia , Fernandes Simon , Velluz Marie-Claire , Kruse Karsten , Aumeier Charlotte
Published: April 2021

Tubulin dimers assemble into dynamic microtubules which are used by molecular motors as tracks for intracellular transport. Organization and dynamics of the microtubule network is commonly thought to be regulated at the polymer ends, where tubulin-dimers can be added or removed. Here we show that molecular motors running on microtubules cause exchange of dimers along the shaft. These sites of dimer exchange act as rescue sites where depolymerising microtubules stop shrinking and start re-growing. Consequently, the average length of microtubules increases depending on how frequently they are used as motor tracks. An increase of motor activity densifies the cellular microtubule network and enhances cell polarity. Running motors leave marks in the shaft serving as traces of microtubule usage to organize the polarity landscape of the cell.
Persistence and expansion of cryptic endangered red wolf genomic ancestry along the American Gulf coast
Authors: vonHoldt Bridgett M. , Brzeski Kristin E. , Aardema Matthew L. , Schell Christopher , Rutledge Linda Y. , Fain Steven R. , Shutt Amy , Linderholm Anna , Murphy William J.
Published: April 2021

Admixture and introgression play a critical role in adaptation and genetic rescue that has only recently gained a deeper appreciation. Here, we explored the geographic and genomic landscape of cryptic ancestry of the endangered red wolf that persists within the genome of a ubiquitous sister taxon, the coyote, all the while the red wolf has been extinct in the wild since the early 1980s. We assessed admixture across 102,621 SNP loci genotyped in 293 canid genomes. We found support for increased red wolf ancestry along an east-to-west gradient across the southern United States that was associated with historical admixture in the past 100 years. Southwestern Louisiana and southeastern Texas, the geographic zone where the last red wolves were known prior to their extinction in the wild, contained the highest and oldest levels of red wolf ancestry. X-linked regions of low recombination rates were depleted of introgression, relative to the autosomes, suggestive of the large X effect and enrichment with loci involved in maintaining reproductive isolation. Recombination rate was positively correlated with red wolf ancestry across coyote genomes, consistent with theoretical predictions. The geographic and genomic extent of cryptic red wolf ancestry can provide novel and variable genomic resources for the survival of the endangered red wolf.
Faster-haplodiploid evolution under divergence-with-gene-flow: simulations and empirical data from pine-feeding hymenopterans
Authors: Bendall Emily E. , Bagley Robin K. , Sousa Vitor C. , Linnen Catherine R.
Published: April 2021

Although haplodiploidy is widespread in nature, the evolutionary consequences of this sex determination mechanism are not well characterized. Here, we examine how genome-wide hemizygosity and a lack of recombination in haploid males affects genomic differentiation in populations that diverge via natural selection while experiencing gene flow. First, we simulated diploid and haplodiploid “genomes” (500-kb loci) evolving under an isolation-with-migration model with mutation, drift, selection, migration, and recombination; and examined differentiation at neutral sites both tightly and loosely linked to a divergently selected site. So long as there is divergent selection and migration, sex-limited hemizygosity and recombination cause elevated differentiation (i.e., produce a “faster-haplodiploid effect”) in haplodiploid populations relative to otherwise equivalent diploid populations, for both recessive and codominant mutations. Second, we used genome-wide SNP data to model divergence history and describe patterns of genomic differentiation between sympatric populations of Neodiprion lecontei and N. pinetum, a pair of pine sawfly species (order: Hymenoptera; family: Diprionidae) that are specialized on different pine hosts. These analyses support a history of continuous gene exchange throughout divergence and reveal a pattern of heterogeneous genomic differentiation that is consistent with divergent selection on many unlinked loci. Third, using simulations of haplodiploid and diploid populations evolving according to the estimated divergence history of N. lecontei and N. pinetum, we found that divergent selection would lead to higher differentiation in haplodiploids. Based on these results, we hypothesize that haplodiploids undergo divergence-with-gene-flow and sympatric speciation more readily than diploids.
Loss of TDP-43 function and rimmed vacuoles persist after T cell depletion in a xenograft model of sporadic inclusion body myositis
Authors: Britson Kyla A. , Ling Jonathan P. , Braunstein Kerstin E. , Montagne Janelle M. , Kastenschmidt Jenna M. , Wilson Andrew , Ikenaga Chiseko , Tsao William , Pinal-Fernandez Iago , Russel Katelyn A. , Reed Nicole , Wagner Kathryn R. , Ostrow Lyle W. , Corse Andrea M. , Mammen Andrew L. , Villalta S. Armando , Larman H. Benjamin , Wong Philip C. , Lloyd Thomas E.
Published: April 2021

Sporadic inclusion body myositis (IBM) is the most common acquired muscle disease in adults over age 50, yet it remains unclear whether the disease is primarily driven by T cell-mediated autoimmunity. IBM muscle biopsies exhibit nuclear clearance and cytoplasmic aggregation of TDP-43 in muscle cells, a pathologic finding observed initially in neurodegenerative disease, and nuclear loss of TDP-43 in neurons causes aberrant RNA splicing. Here, we show that loss of TDP-43 splicing repression, as determined by inclusion of cryptic exons, occurs in skeletal muscle of IBM patients. Out of 119 muscle biopsies tested, RT-PCR-mediated detection of cryptic exon expression is 84% sensitive and 99% specific for diagnosing IBM, indicating utility as a functional and diagnostic biomarker. To determine the role of T cells in pathogenesis, we generated a novel xenograft model by transplanting human IBM muscle into the hindlimb of immunodeficient mice. Xenografts from IBM patients display robust regeneration of human myofibers and recapitulate both inflammatory and degenerative features of the disease. Myofibers in IBM xenografts are invaded by human, oligoclonal CD8+ T cells and exhibit MHC-I upregulation, rimmed vacuoles, mitochondrial pathology, p62-positive inclusions, and nuclear clearance and cytoplasmic aggregation of TDP-43, resulting in expression of cryptic exons. Depletion of human T cells within IBM xenografts by treating mice intraperitoneally with anti-CD3 (OKT3) suppresses MHC-I upregulation, but rimmed vacuoles and loss of TDP-43 function persist. These data suggest that myofiber degeneration occurs independent of T cells, and muscle cell-intrinsic mechanisms, such as loss of TDP-43 splicing repression, drive IBM pathogenesis.

One Sentence Summary

Depletion of T cells in a xenograft model of sporadic inclusion body myositis suppresses inflammation but not TDP-43 pathology or muscle degeneration.
Integrating Rigidity Analysis into the Exploration of Protein Conformational Pathways using RRT* and MC
Authors: Afrasiabi Fatemeh , Dehghanpoor Ramin , Haspel Nurit
Published: April 2021

To understand how proteins function on a cellular level, it is of paramount importance to understand their structures and dynamics, including the conformational changes they undergo to carry out their function. For the aforementioned reasons, the study of large conformational changes in proteins has been an interest to researchers for years. However, since some proteins experience rapid and transient conformational changes, it is hard to experimentally capture the intermediate structures. Additionally, computational brute force methods are computationally intractable, which makes it impossible to find these pathways which require a search in a high-dimensional, complex space. In our previous work, we implemented a hybrid algorithm that combines Monte-Carlo (MC) sampling and RRT*, a version of the Rapidly Exploring Random Trees (RRT) robotics-based method, to make the conformational exploration more accurate and efficient, and produce smooth conformational pathways. In this work, we integrated the rigidity analysis of proteins into our algorithm to guide the search to explore flexible regions. We demonstrate that rigidity analysis dramatically reduces the run time and accelerates convergence.
Acquisition of cellular properties during alveolar formation requires differential activity and distribution of mitochondria
Authors: Zhang Kuan , Yao Erica , Wong Julia , Wolters Paul J. , Chuang Pao-Tien
Published: April 2021

Alveolar formation requires coordinated movement and interaction between alveolar epithelial cells, mesenchymal myofibroblasts and endothelial cells/pericytes to produce secondary septa. These processes rely on the acquisition of distinct cellular properties to enable ligand secretion for cell-cell signaling and initiate morphogenesis through cell migration and cell shape change. In this study, we showed that mitochondrial activity and distribution play a key role in bestowing cellular functions on both alveolar epithelial cells and mesenchymal myofibroblasts for generating secondary septa to form alveoli. These results suggest that mitochondrial function is tightly regulated to empower cellular machineries in a spatially specific manner. Indeed, such regulation via mitochondria is required for secretion of platelet-derived growth factor from alveolar epithelial cells to influence myofibroblast proliferation and migration. Moreover, mitochondrial function enables myofibroblast migration during alveolar formation. Together, these findings yield novel mechanistic insights into how mitochondria regulate pivotal steps of alveologenesis. They highlight selective utilization of energy and diverse energy demands in different cellular processes during development. Our work serves as a paradigm for studying how mitochondria control tissue patterning.
Discovery of bactericides as an acute mitochondrial membrane damage inducer
Authors: Houston Ryan , Sekine Yusuke , Larsen Mads B , Murakami Kei , Narendra Derek P , Chen Bill B , Sekine Shiori
Published: April 2021

Mitochondria evolved from endosymbiotic bacteria to become essential organelles of eukaryotic cells. The defined lipid composition and structure of mitochondrial membranes are critical for the proper functioning of mitochondria. However, mitochondrial stress responses that help maintain the integrity of mitochondrial membranes against internal or external insults are not well understood. One reason for this lack of insight is the absence of efficient tools to specifically damage mitochondrial membranes. Here, through a compound screen originally aimed at identifying inhibitors of the inner mitochondrial membrane (IMM)-resident protease OMA1, we found that two bis-biguanide compounds, Chlorhexidine and Alexidine, modified OMA1 activity by altering the integrity of the IMM. Interestingly, these compounds are well-known bactericides whose mechanism of action has centered on their damage-inducing activity on bacterial membranes. We found Alexidine binds to the IMM likely through the electrostatic interaction driven by the membrane potential as well as an affinity for anionic phospholipids. Electron microscopic analysis revealed that Alexidine severely perturbated the IMM, especially the cristae structure. Along with this, we observed the altered localization of IMM-resident membrane-shaping proteins, including Mic60. Notably, Alexidine evoked a specific transcriptional/proteostasis signature that was not induced by other typical mitochondrial stressors, highlighting the unique property of Alexidine as a novel mitochondrial membrane stressor. Our findings provide a chemical-biological tool that can induce acute and selective perturbation of the IMM integrity, which should enable the delineation of mitochondrial stress-signaling pathways required to maintain the mitochondrial membrane homeostasis.
The herpes simplex virus 1 protein ICP4 acts as both an activator and repressor of host genome transcription during infection
Authors: Rivas Thomas , Goodrich James A. , Kugel Jennifer F.
Published: April 2021

Infection by Herpes simplex virus 1 (HSV-1) impacts nearly all steps of gene expression in the host cell. The regulatory mechanisms by which this occurs, and the interplay between host and viral factors, have yet to be fully elucidated. Here we investigated how the occupancy of RNA polymerase II (Pol II) on the host genome changes during HSV-1 infection and is impacted by the viral immediate early protein ICP4. Pol II ChIP-seq experiments revealed a reduction of Pol II occupancy across the bodies of hundreds of host genes that was dependent upon ICP4. Concomitantly, Pol II levels increased across the bodies of several hundred genes, the majority of which also depended on ICP4 for activation. Our data suggest ICP4 regulates repression of Pol II at host genes by inhibiting recruitment of Pol II, while it regulates activation by promoting release of Pol II from promoter proximal pausing into productive elongation. Consistent with this, relative levels of the pausing factors NELF-A and Spt5 were reduced on an HSV-1 activated gene in an ICP4 dependent manner. Exogenous expression of ICP4 revealed that ICP4 can activate, but not repress, transcription of some genes in the absence of infection in a manner that correlates with the chromatin state of the gene. Together our data support the model that ICP4 decreases promoter proximal pausing on host genes activated by infection, and ICP4 is necessary, but not sufficient, to repress transcription from host genes during viral infection.
On the mechanical regulation of epithelial tissue homeostasis
Authors: Kaliman Sara , Hubert Maxime , Wollnik Carina , Nuić Lovro , Vurnek Damir , Gehrer Simone , Lovrić Jakov , Dudziak Diana , Rehfeldt Florian , Smith Ana-Sunčana
Published: April 2021

Despite recent efforts to understand homeostasis in epithelial tissues, there are many unknowns surrounding this steady state. It is considered to be regulated by mechanoresponse, but unlike for single cells, this remains heavily debated for tissues. Here, we show that changes in matrix stiffness induce a non-equilibrium transition from tubular to squamous Madin-Darby Canine Kidney II tissues. Nonetheless, despite different cell morphologies and densities, all homeostatic tissues display equivalent topologies, which, hence, must be actively targeted and regulated. On the contrary, the mechanoresponse induces dramatic changes in the large-scale organization of the colonies. On stiff gels, this yields an unreported cooperative state of motile cells displaying higher densities than in the arrested homeostatic state. This suggests a more complex relation between cell density and motility than previously anticipated. Our results unequivocally relate the mechanosensitive properties of individual cells to the evolving macroscopic structures, an effect that could be important for understanding the emergent pathologies of living tissues.
Microvesicles Transfer Mitochondria and Increase Mitochondrial Function in Brain Endothelial Cells
Authors: D’Souza Anisha , Burch Amelia , Dave Kandarp M. , Sreeram Aravind , Reynolds Michael J. , Dobbins Duncan X. , Kamte Yashika S. , Zhao Wanzhu , Sabatelle Courtney , Joy Gina M. , Soman Vishal , Chandran Uma R. , Shiva Sruti S. , Quillinan Nidia , Herson Paco S. , Manickam Devika S
Published: April 2021

We have demonstrated, for the first time that microvesicles, a sub-type of extracellular vesicles (EVs) derived from hCMEC/D3: a human brain endothelial cell (BEC) line transfer polarized mitochondria to recipient BECs in culture and to neurons in mice acute brain cortical and hippocampal slices. This mitochondrial transfer increased ATP levels by 100 to 200-fold (relative to untreated cells) in the recipient BECs exposed to oxygen-glucose deprivation, anin vitromodel of cerebral ischemia. We have also demonstrated that transfer of microvesicles, the larger EV fraction, but not exosomes resulted in increased mitochondrial function in hypoxic endothelial cultures. Gene ontology and pathway enrichment analysis of EVs revealed a very high association to glycolysis-related processes. In comparison to heterotypic macrophage- derived EVs, BEC-derived EVs demonstrated a greater selectivity to transfer mitochondria and increase endothelial cell survival under ischemic conditions.

Highlights

Microvesicles transfer mitochondria to endothelial cells and brain slice neurons

Mitochondrial transfer increased ATP in ischemic brain endothelial cells (BECs)

Transfer of microvesicles increased mitochondrial function in hypoxic BECs

Transfer of exosomes did not affect mitochondrial function in hypoxic BECs

Homotypic BEC-derived EVs result in greater ATP levels in the recipient BECs
ADAM17 inhibition prevents neutrophilia and lung injury in a mouse model of Covid-19
Authors: Lartey Nathaniel L. , Valle-Reyes Salvador , Vargas-Robles Hilda , Jiménez-Camacho Karina E. , Guerrero-Fonseca Idaira M. , Castellanos-Martínez Ramón , Montoya-García Armando , García-Cordero Julio , Cedillo-Barrón Leticia , Nava Porfirio , Filisola-Villaseñor Jessica G. , Roa-Velázquez Daniela , Zavala-Vargas Dan I , Morales-Ríos Edgar , Salinas-Lara Citlaltepetl , Vadillo Eduardo , Schnoor Michael
Published: April 2021

Severe coronavirus disease 2019 (Covid-19) is characterized by lung injury, cytokine storm and increased neutrophil-to-lymphocyte ratio (NLR). Current therapies focus on reducing viral replication and inflammatory responses, but no specific treatment exists to prevent the development of severe Covid-19 in infected individuals. Angiotensin-converting enzyme-2 ACE-2) is the receptor for SARS-CoV-2, the virus causing Covid-19, but it is also critical for maintaining the correct functionality of lung epithelium and endothelium. Coronaviruses induce activation of a disintegrin and metalloprotease 17 (ADAM17) and shedding of ACE-2 from the cell surface resulting in exacerbated inflammatory responses. Thus, we hypothesized that ADAM17 inhibition ameliorates Covid-19-related lung inflammation. We employed a pre-clinical mouse model using intra-tracheal instillation of a combination of polyinosinic:polycytidylic acid (poly-I:C) and the receptor-binding domain of the SARS-CoV-2 spike protein (RBD-S) to mimic lung damage associated with Covid-19. Histological analysis of inflamed mice confirmed the expected signs of lung injury including edema, fibrosis, vascular congestion and leukocyte infiltration. Moreover, inflamed mice also showed an increased NLR as observed in critically ill Covid-19 patients. Administration of the ADAM17 inhibitors apratastat and TMI-1 significantly improved lung histology and prevented leukocyte infiltration. Reduced leukocyte recruitment could be explained by reduced production of pro-inflammatory cytokines and lower levels of the endothelial adhesion molecules ICAM-1 and VCAM-1. Additionally, the NLR was significantly reduced by ADAM17 inhibition. Thus, we propose inhibition of ADAM17 as a novel promising treatment strategy in SARS-CoV-2-infected individuals to prevent the progression towards severe Covid-19.
DDN2.0: R and Python packages for differential dependency network analysis of biological systems
Authors: Zhang Bai , Fu Yi , Lu Yingzhou , Zhang Zhen , Clarke Robert , Van Eyk Jennifer E. , Herrington David M. , Wang Yue
Published: April 2021

Data-driven differential dependency network analysis identifies in a complex and often unknown overall molecular circuitry a network of differentially connected molecular entities (pairwise selective coupling or uncoupling depending on the specific phenotypes or experimental conditions) (Herrington, et al. 2018; Zhang, et al., 2009; Zhang and Wang, 2010; Zhang, et al., 2016). Such differential dependency networks are typically used to assist in the inference of potential key pathways. Based on our previously developed Differential Dependency Network (DDN) method, we report here the fully implemented R and Python software tool packages for public use. The DDN2.0 algorithm uses a fused Lasso model and block-wise coordinate descent to estimate both the common and differential edges of dependency networks. The identified DDN can help to provide plausible interpretation of data, gain new insight of disease biology, and generate novel hypotheses for further validation and investigations.

To address the imbalanced sample group problem, we propose a sample-size normalized formulation to correct systematic bias. To address high computational complexity, we propose four strategies to accelerate DDN2.0 learning. The experimental results show that new DDN2.0+ learning speed with combined four accelerating strategies is hundreds of times faster than that of DDN2.0 algorithm on medium-sized data (Fu, 2019). To detect intra-omics and inter-omics network rewiring, we propose multiDDN using a multi-layer signaling model to integrate multi-omics data. The simulation study shows that the multiDDN method can achieve higher accuracy of detecting network rewiring (Fu, 2019).
Designing a high-resolution, LEGO-based microscope for an educational setting
Authors: Vos Bart E. , Blesa Emil Betz , Betz Timo
Published: April 2021

Microscopy is an essential tool in many fields of science. However, due to their costs and fragility, the usage of microscopes is limited in classroom settings and nearly absent at home. In this article we present the construction of a microscope using LEGO®bricks and low-cost, easily available lenses. We demonstrate that the obtained magnification and resolution are sufficient to resolve micrometer-sized objects and propose a series of experiments that explore various biophysical principles. Finally, a study with students in the age range of 9 to 13 shows that the understanding of microscopy increases significantly after working with the LEGO microscope.
Dorsomedial hypothalamic BDNF neurons integrate thermal afferent signals to control energy expenditure
Authors: Zhou Qian , Bian Hao , Wang Mengting , Ni Xinyan , Yang Wen Z. , Sun Hongbin , Shen Wei L.
Published: April 2021

Mutations in the gene brain-derived neurotrophic factor (BDNF) cause obesity in humans. BDNF signaling and its expressing neurons in the hypothalamus help control feeding, energy expenditure (EE), and physical activity. However, whether the BDNF neurons interact with another EE-regulating system, the thermoregulation circuitry, remains unclear. Here, we show that BDNF neurons in the dorsomedial hypothalamus (DMH) are activated by environmental cooling and sufficient to induce body temperature increases and brown adipose tissue (BAT) thermogenesis. Conversely, blocking these neurons impairs BAT thermogenesis and cold defense, causing body weight gain and glucose intolerance. DMH BDNF neurons are therefore an important type of thermoregulatory neuron, integrating thermal afferent signals to control EE during cold defense. This reveals a critical intersection between the BDNF circuitry and the thermoregulatory system.
The economic order quantity model with inspection policy of zero-defect single sampling
Authors: Nakhaeinejad Mahdi
Published: April 2021

Purpose

This paper proposes a new inventory model with inspection policy because in practice the received orders may contain non- conforming (NC) items. So, a buyer who receive an order from a supplier should use an inspection policy.

Design/methodology/approach

The inspection policy is assumed to be zero-defect single sampling. Under this policy a lot is accepted only if no defect has been identified in the inspected sample. The fraction of NC is assumed to be a random variable following a Binomial distribution and the number of NC items detected by inspection assumed to be a random variable, which follows a hypergeometric distribution. Order quantity and sample size are the two decision variables. A solution procedure is presented for the proposed model. The proposed procedure presents the optimal solution.

Findings

Numerical examples presented to illustrate the procedure outlined for the proposed model and its applicability. The results of numerical examples and comparing them with traditional EOQ model reveal that by the proposed model, the buyer could reduce total cost that shows the efficiency and validity of the proposed model.

Originality/value

The novelty of this paper is the new proposed model that considers inspection policy in inventory management. The proposed model determines sample size as well as order quantity to consider both subject of inventory management and quality control, simultaneously.
Body size determines the thermal coupling between insects and plant surfaces
Authors: Pincebourde Sylvain , Dillon Michael E. , Woods H. Arthur
Published: April 2021

Most studies in global change biology predict biological impacts of warming from information on macroclimates. Most organisms, however, live in microhabitats with physical conditions which are decoupled to varying degrees from those in macroclimates depending partly on organism body size.

Small ectotherms of a few millimetres in length live deep in surface boundary layers such that their heat budgets are dominated by different processes compared to larger ectotherms, whose bodies emerge from surface boundary layers. We therefore hypothesized that the body size relative to surface boundary layer thickness generates different patterns of body temperature variation for organisms in the same nominal habitats.

We tested this hypothesis in a community of arthropods living on a subalpine plant by combining physical models to acquire high‐resolution time series of operative temperatures, thermal imaging to assess the strength of coupling between physical models or arthropod bodies and surrounding leaf temperatures, and a cross‐scale approach to infer the temperature distributions available to small ectotherms.

The size of the physical model strongly influenced operative temperature dynamics: the bigger, the warmer. Small models were just a few degrees warmer than leaf surfaces, whereas large models deviated from leaf temperature by >10°C.

We found similar patterns of body temperature of naturally occurring arthropods. Temperatures of small insects closely tracked leaf surface temperatures even in full sun, whereas larger insects were warmer than leaf surfaces.

At the whole plant scale, the thermal diversity of leaf surfaces was high, especially in the sun, typically generating a range of microclimatic temperatures (for small insects) of >10°C. Larger insects instead could move between shaded and sunny portions of the whole plant to vary body temperatures by a larger extent.

The bulk of animal biodiversity consists of small terrestrial arthropods, the majority of which are associated with plant surfaces at some point in their life cycles. The distribution of body sizes determines how much thermal diversity is available for behavioural thermoregulation, thereby contributing to their potential response to climate change.

A free Plain Language Summary can be found within the Supporting Information of this article.
Potentially peat‐forming biomass of fen sedges increases with increasing nutrient levels
Authors: Hinzke Tjorven , Li Guixiang , Tanneberger Franziska , Seeber Elke , Aggenbach Camiel , Lange Jelena , Kozub Łukasz , Knorr Klaus‐Holger , Kreyling Juergen , Kotowski Wiktor
Published: April 2021

Peat formation is a key carbon sequestration process in the terrestrial biosphere. In temperate fens, peat is mainly formed by below‐ground biomass of vascular plants. Nutrient availability in temperate fens is naturally variable, and nowadays increasing due to atmospheric deposition, runoff from agriculture and mineralization of peat caused by drainage. To maintain or restore peat formation, it is important to understand how increased nutrient availability influences the main controls of peat formation, that is, below‐ground biomass production and decomposition.

We investigated above‐ and below‐ground biomass production and decomposition of five fen sedges (Carex spp.) grown under 12 different nutrient levels (realized with nitrogen amounts increasing exponentially across levels, with addition of phosphorous and potassium to ensure nitrogen limitation in each nutrient level) in a mesocosm experiment, designed to resemble a gradient of very low to very high nutrient availabilities in temperate fens. In addition, we measured nutrient stoichiometry in the biomass and related this to possible growth limitations and to root decomposition.

Our results indicate that higher biomass production at higher nutrient levels was not offset by an increase in decomposition. Increase of above‐ and below‐ground biomass with higher nutrient levels was species‐specific. Decomposition of standardized plant material in mesocosms was not dependent on the species growing in the mesocosms and showed only slight, if any, variation with differing nutrient levels. Decomposition of roots grown under different nutrient levels was mainly correlated with species identity and root lignin:cellulose ratio.

Our study suggests that the Carex spp. potentially peat‐forming root biomass, here defined as the root biomass which is not decomposed during one growing season, increases with increasing nutrient levels: higher root biomass production is not counteracted by increasing decomposition during the growing season. Based on this pattern of positive mass balance in five common sedge species with differing growth characteristics, we propose that sedge communities establishing after rewetting have the potential for renewed peat formation regardless of the prevailing trophic level.

A free Plain Language Summary can be found within the Supporting Information of this article.
Gravity inversion of 2D fault having variable density contrast using particle swarm optimization
Authors: Roy Arka , Kumar Thatikonda Suresh
Published: April 2021

A Matlab‐based optimization algorithm is introduced for inverting fault structures from observed gravity anomalies. A convenient graphical user interface is also presented for incorporating the input parameters without any technical complexity to any users. The inversion code uses particle swarm optimization, and all control parameters are tuned initially for faster convergence. There is no requirement of prior choice of an initial model, that is the advantage of using global optimization. The optimization technique is versatile enough to handle any depth‐varying density distributions. The maximum number of iterations and stopping criterion is fixed initially for getting the best optimized solution. The inverted model's output in terms of fault structure, observed and inverted gravity anomalies and dip, and vertex location of fault plane can be viewed in the graphical user interface at the end of the optimization process. The optimization algorithm is applied to different synthetic models with fixed and depth‐varying density contrasts. All synthetic models are further contaminated with white Gaussian noise for sensitivity analysis, and detailed uncertainty appraisal was also performed for the reliability estimation. Finally, the optimization is implemented for fault structure inversion of the Aswaraopet boundary fault, India, and found that the optimized solution provides a good agreement with the previously published literature. Optimized results indicate that this novel optimization approach demonstrates a robust implementation of fault inversion for any depth‐varying density distributions.
Individual‐based simulations of genome evolution with ancestry: The GenomeAdmixR R package
Authors: Janzen Thijs , Diaz Fernando
Published: April 2021

Hybridization between populations or species results in a mosaic of the two parental genomes. This and other types of genome admixture have received increasing attention for their implications in speciation, human evolution, Evolve and Resequence (E&R) and genetic mapping. However, a thorough understanding of how local ancestry changes after admixture and how selection affects patterns of local ancestry remains elusive. The complexity of these questions limits analytical treatment, but these scenarios are specifically suitable for simulation.

Here, we present the R package GenomeAdmixR, which uses an individual‐based model to simulate genomic patterns following admixture forward in time. GenomeAdmixR provides user‐friendly functions to set up and analyse simulations under evolutionary scenarios with selection, linkage and migration.

We show the flexible functionality of the GenomeAdmixR workflow by demonstrating (a) how to design an E&R simulation using GenomeAdmixR and (b) how to use GenomeAdmixR to verify analytical expectations following from the theory of junctions.

GenomeAdmixR provides a mechanistic approach to explore expected genome responses to realistic admixture scenarios. With this package, we aim to aid researchers in testing specific hypotheses based on empirical findings involving admixing populations.
Iron deficiency anaemia and early childhood caries: a cross‐sectional study
Authors: Mohamed WE , Abou El Fadl RK , Thabet RA , Helmi M , Kamal SH
Published: April 2021

Background

This study aimed to assess the association between iron deficiency anaemia (IDA) and dental caries in early childhood.

Methods

A total of 40 children with proven IDA and another 40 healthy age and sex‐matched children were enrolled in this cross‐sectional study. Legal guardians were interviewed to collect data on oral hygiene measures and dietary habits. Anthropometric measurements were performed for all participants, and blood samples were collected to assess complete blood count and body iron status. Patients were confirmed to have IDA based on haemoglobin level (Hb), red blood cells indices and body iron status. Caries experience was determined based on the number of decayed, missing and filled primary teeth using dmft index.

Results

A statistically significant negative correlation between dmft index scores and haemoglobin level (r = −0.454, P < 0.001) and mean corpuscular haemoglobin (MCH) level (r = −0.380, P = 0.001) was detected, and in accordance there was a positive statistically significant correlation between caries experience and the presence of anaemia (r = −0.60, P < 0.001).

Conclusion

In early childhood, dental caries might coexist with IDA even in its mildest form. All children exhibiting severe early childhood caries should be investigated for IDA and anaemia should be managed if present.
Elective node dissection versus observation for management of patients with early‐stage cT1/T2N0 tongue carcinoma: A systematic review and meta‐analysis of prospective studies
Authors: Alsini Albaraa Y. , Alsubaie Hemail M. , Marzouki Hani Z. , Abu‐Zaid Ahmed , Al‐Qahtani Khalid
Published: April 2021

Objective

To carry out a meta‐analysis of prospective literature comparing the clinical efficacy of elective neck dissection (END) vs observation (OBS) in patients with early‐stage cT1/T2N0 tongue carcinoma.

Design/Setting/Participants/Outcome Measures

We systematically reviewed four databases from inception to 30‐October‐2020. We considered all studies meeting the following PICOS conditions: (a) Patients: early‐stage cT1/T2N0 tongue carcinoma, (b) Intervention: END, (c) Comparator: OBS, (d) Outcomes: local tongue recurrence, cervical nodal recurrence, disease‐specific survival (DSS) rate, and disease‐free survival (DFS) rate and (e) Study design: prospective reports. We pooled dichotomous data as relative risks (RRs) with 95% confidence intervals (CIs).

Results

Four studies (one case‐control study and three randomised controlled trials) met our inclusion criteria. There were 448 eligible patients (225 and 223 patients were treated with END and OBS, respectively). END significantly correlated with improved DSS rate (RR = 1.15, 95% CI: 1.04‐1.27, P = .007). Nonetheless, there were no significant differences between END and OBS groups regarding the rates of local tongue recurrence (RR = 1.23, 95% CI: 0.50‐3.03, P = .65), cervical nodal recurrence (RR = 0.45, 95% CI: 0.16‐1.27, P = .13) and DFS rate (RR = 1.08, 95% CI: 0.91‐1.27, P = .38). Pooled analysis for cervical nodal recurrence was heterogeneous, and sensitivity analysis revealed a significantly lower cervical nodal recurrence rate in favour of END group (RR = 0.30, 95% CI: 0.13‐0.67, P = .004).

Conclusion

END correlated with a significant decrease in cervical nodal recurrence and improved DSS rate. END might be superior to OBS in patients with early‐stage cT1/T2N0 tongue cancer.
Hippocampal glucocorticoid target genes associated with enhancement of memory consolidation
Authors: Buurstede Jacobus C. , van Weert Lisa T.C.M. , Colucci Paola , Gentenaar Max , Viho Eva M.G. , Koorneef Lisa L. , Schoonderwoerd Robin A. , Lanooij Suzanne D. , Moustakas Ioannis , Balog Judit , Mei Hailiang , Kielbasa Szymon M. , Campolongo Patrizia , Roozendaal Benno , Meijer Onno C.
Published: April 2021

Glucocorticoids enhance memory consolidation of emotionally arousing events via largely unknown molecular mechanisms. This glucocorticoid effect on the consolidation process also requires central noradrenergic neurotransmission. The intracellular pathways of these two stress mediators converge on two transcription factors: the glucocorticoid receptor (GR) and phosphorylated cAMP response element‐binding protein (pCREB). We therefore investigated, in male rats, whether glucocorticoid effects on memory are associated with genomic interactions between the GR and pCREB in the hippocampus. In a two‐by‐two design, object exploration training or no training was combined with post‐training administration of a memory‐enhancing dose of corticosterone or vehicle. Genomic effects were studied by chromatin immunoprecipitation followed by sequencing (ChIP‐seq) of GR and pCREB 45 min after training and transcriptome analysis after 3 hr. Corticosterone administration induced differential GR DNA‐binding and regulation of target genes within the hippocampus, largely independent of training. Training alone did not result in long‐term memory nor did it affect GR or pCREB DNA‐binding and gene expression. No strong evidence was found for an interaction between GR and pCREB. Combination of the GR DNA‐binding and transcriptome data identified a set of novel, likely direct, GR target genes that are candidate mediators of corticosterone effects on memory consolidation. Cell‐specific expression of the identified target genes using single‐cell expression data suggests that the effects of corticosterone reflect in part non‐neuronal cells. Together, our data identified new GR targets associated with memory consolidation that reflect effects in both neuronal and non‐neuronal cells.
How does the affordable care act Medicaid expansion affect cigarette consumption?—The mechanism and heterogeneity
Authors: Wang Lingxiao , Zheng Yuqing , Buck Steven C.
Published: April 2021

We examine the average effect of the affordable care act (ACA) Medicaid expansion on cigarette consumption as well as heterogeneous effects by consumer types, depending on whether they use anti‐smoking products and their baseline level of cigarette consumption. Using the Nielsen homescan consumer panel and generalized difference‐in‐differences (GDD) method, we find that anti‐smoking products can induce cigarette smoking among moderate and heavy smokers. However, the ACA Medicaid expansion reduces cigarette smoking through channels other than anti‐smoking products. As a net result, the ACA Medicaid expansion leads to a reduction in smoking. Light smokers are the main beneficiaries of ACA Medicaid expansion—their average cigarette consumption reduces by over one pack per month.
Clinical Performance of CAD/CAM Monolithic Lithium Disilicate Implant‐Supported Single Crowns Using Solid or Predrilled Blocks in a Fully Digital Workflow: A Retrospective Cohort Study With Up To 33 Months of Follow Up
Authors: Bompolaki Despoina , Punj Amit , Fellows Christopher , Truong Christina , Ferracane Jack L.
Published: April 2021

Purpose

To assess the clinical performance of CAD/CAM monolithic implant‐supported restorations manufactured using a fully digital workflow and two different types of ceramic blocks.

Materials and Methods

One hundred and one patients received single‐unit implant‐supported restorations at a University predoctoral clinic. All restorations were designed and fabricated using either a predrilled LS2 block (group P, n = 59) or a conventional solid LS2 block with an occlusal opening drilled manually prior to crystallization (group M, n = 42). The mean follow‐up time after restoration delivery was 18.4 ± 4.8 months (range 12 to 33 months). Patients with less than a 12‐month follow‐up were excluded. Electronic health records were reviewed to identify number and type of complications during the follow‐up time. Clinical outcomes were classified as success, survival, and failure of the restoration. Chi‐square tests were used to identify differences in success and survival rates between the groups. Nonparametric Mann‐Whitney U tests were used to identify differences in the number of major and minor complications as well as the total number of complications that were observed among groups.

Results

Overall success and survival rates were 80.2% and 97%, respectively. Seventy one restorations (70.3%) were complication‐free. There were no significant differences between the groups with regards to the number of complications or success and survival rates.

Conclusions

Single‐unit CAD/CAM monolithic implant‐supported restorations that are fabricated in a fully digital workflow present relatively high complication rates and moderate short‐term clinical outcomes. Clinical studies with longer follow‐up times are needed to evaluate long‐term outcomes of these restorations.
Substitution of histone H3 arginine 72 to alanine leads to the deregulation of isoleucine biosynthesis in the budding yeast Saccharomyces cerevisiae
Authors: Thakre Pilendra Kumar , Sahu Rakesh Kumar , Tomar Raghuvir Singh
Published: April 2021

Histone residues play an essential role in the regulation of various biological processes. In the present study, we utilized the H3/H4 histone mutant library to probe the functional aspects of histone residues in amino acid biosynthesis. We found that the histone residue H3R72 plays a crucial role in the regulation of isoleucine biosynthesis. Substitution of the arginine residue (H3R72) of histone H3 to alanine (H3R72A) renders yeast cells unable to grow in minimal medium. Histone mutant H3R72A requires external supplementation of either isoleucine, serine, or threonine for growth in minimal medium. We also observed that the H3R72 residue and leucine amino acid in synthetic complete medium might play a crucial role in determining the intake of isoleucine and threonine in yeast. Furthermore, gene deletion analysis of ILV1 and CHA1 in the H3R72A mutant confirmed that isoleucine is the sole requirement for growth in minimal medium. Altogether, we have identified that histone H3R72 residue may be crucial for yeast growth in minimal medium by regulating isoleucine biosynthesis through the Ilv1 enzyme in the budding yeast Saccharomyces cerevisiae.
Stakeholder Analysis in the Feasibility Process of Projects: A Structural Evaluation of the Power-Oriented Relationship
Authors: Sarhadi Mehrdad , Hasanzadeh Sogand , Hoseini Seyed Hosein
Published: April 2021

The feasibility process of public construction projects is under the influence of stakeholders, who give direction to public resource allocation. Therefore, the analysis of stakeholders in this process is critical. An inductive qualitative approach was adopted using the grounded theory method to provide a theoretical explanation of stakeholders’ behaviors. Under the insight of structuration theory, the results indicated that the challenges are derived from various interrelated factors, leading to the emergence of improper participation as a macro-structural phenomenon with multilateral interaction with a power-oriented relationship as a micro behavior in the feasibility process at the agency level.
Characterization of fosfomycin resistance and molecular epidemiology among carbapenem-resistant Klebsiella pneumoniae strains from two tertiary hospitals in China
Authors: Wang Haichen , Min Changhang , Li Jun , Yu Ting , Hu Yongmei , Dou Qingya , Zou Mingxiang
Published: April 2021

Background

Fosfomycin has been proven to be a vital choice to treat infection caused by multidrug resistance bacteria, especially carbapenem-resistant Klebsiella pneumoniae (CRKP). However, fosfomycin resistant cases has been reported gradually. In this study, we reported the fosfomycin-resistant rate in CRKP strains and further revealed the molecular mechanisms in resistance gene dissemination.

Results

A total of 294 non-duplicated CRKP strains were collected. And 55 fosfomyin-resistant strains were detected, 94.5% of which were clustered to sequence type (ST) 11 by PCR followed up sequencing. PFGE further revealed two major groups and four singletons. The positive rates of genes responsible to fosfomycin and carbapenem resistance were 81.8% (fosA3), 12.7% (fosA5) and 94.5% (blaKPC-2), respectively. Genomic analysis confirmed insertion sequence (IS) 26 was the predominant structure surrounding fosA3. The fosA3 genes in six isolates were located on plasmids which were able to transfer to E. coli J53 recipient cells by means of conjugation.

Conclusions

Although the resistant rate of CRKP to fosfomycin is relatively low in our area, considering its gene is located on transferrable plasmid and inserted in IS structure, continuous monitoring is still needed.