bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractAlveolar 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

AbstractMitochondria 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

AbstractInfection 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

AbstractDespite 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

AbstractWe 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.HighlightsMicrovesicles transfer mitochondria to endothelial cells and brain slice neuronsMitochondrial transfer increased ATP in ischemic brain endothelial cells (BECs)Transfer of microvesicles increased mitochondrial function in hypoxic BECsTransfer of exosomes did not affect mitochondrial function in hypoxic BECsHomotypic 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

AbstractSevere 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

SummaryData-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

AbstractMicroscopy 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

AbstractMutations 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

PurposeThis 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/approachThe 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.FindingsNumerical 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/valueThe 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

Abstract

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

Abstract

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

ABSTRACTA 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.