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opencc-by-4.0Apr 2022View details →

Substrate stiffness reduces particle uptake by epithelial cells and macrophages in a size-dependent manner through mechanoregulation

Cells continuously exert forces on their environment and respond to changes in mechanical forces by altering their behavior. Many pathologies such as cancer and fibrosis are hallmarked by dysregulation in the extracellular matrix, driving aberrant behavior through mechanotransduction pathways. We demonstrate that substrate stiffness can be used to regulate cellular endocytosis of particles in a size-dependent fashion. Culture of A549 epithelial cells and J774A.1 macrophages on polystyrene/glass (stiff) and polydimethylsiloxane (soft) substrates indicated that particle uptake is increased up to six times for A549 and two times for macrophages when cells are grown in softer environments. Furthermore, we altered surface characteristics through the attachment of submicron-sized particles as a method to locally engineer substrate stiffness and topography. To investigate the biomechanical changes which occurred within adherent epithelial cells, i.e. characterization of A549 cell spreading and focal adhesion maturation. Consequently, decreasing substrate rigidity and particle-based topography lead to a reduction of focal adhesion size. Moreover, expression levels of Yes-associated protein were found to correlate with the degree of particle endocytosis. A thorough appreciation of the mechanical cues may lead to improved solutions to optimize nanomedicine approaches for treatment of cancer and other diseases with abnormal mechanosignaling.

A neural substrate for negative affect dictates female parental behavior

Parental behaviors secure the well-being of newborns and concomitantly limit negative affective states in adults, which emerge when coping with neonatal distress becomes challenging. Whether negative-affect-related neuronal circuits orchestrate parental actions is unknown. Here, we identify parental signatures in lateral habenula neurons receiving bed nucleus of stria terminalis innervation (BNSTLHb). We find that LHb neurons of virgin female mice increase their activity following pup distress vocalization and are necessary for pup-call-driven aversive behaviors. LHb activity rises during pup retrieval, a behavior worsened by LHb inactivation. Intersectional cell identification and transcriptional profiling associate BNSTLHb cells to parenting and outline a gene expression in female virgins similar to that in mothers but different from that in non-parental virgin male mice. Finally, tracking and manipulating BNSTLHb cell activity demonstrates their specificity for encoding negative affect and pup retrieval. Thus, a negative affect neural circuit processes newborn distress signals and may limit them by guiding female parenting.

AlphaFold-Multimer (v3) model of a complex of Protein Phosphatase 2A catalytic subunit (PP2A/C), PP2A scaffold subunit (PP2A/A), the B55alpha substrate binding subunit, and FAM122A, a PP2A inhibitor protein.

AlphaFold-Multimer (v3) model structure of a complex of Protein Phosphatase 2A catalytic subunit (PP2A/C), PP2A scaffold subunit (PP2A/A), the B55alpha substrate binding subunit, and FAM122A, a PP2A inhibitor protein. The protein sequences were obtained from UniProt: P67775 · PP2AA_HUMAN P30153 · 2AAA_HUMAN P63151 · 2ABA_HUMAN Q96E09 · PBIR1_HUMAN Coordinates are in mmCIF format. A PyMOL session file is included. Modeling was performed with AlphaFold-Multimer v3, downloaded from DeepMind's github. Structure prediction was performed without templates. The model was relaxed with Amber. FAM122A binds using a short linear motif (SLIM) (residues 84-89) first identified in RBL1 (p107) (Fowle et al., eLife, <a href="https://doi.org/10.7554/eLife.63181">https://doi.org/10.7554/eLife.63181</a> in the form of a short alpha helix (residues 84-92). This is followed by a long alpha helix (residues 96-122) which blocks access to the active site of the catalytic subunit. There are further contacts of FAM122A (residues 150-170) with one of the beta sheets of the B55alpha beta propeller domain. FAM122A regulates PP2A activity during the cell cycle.

Surface acoustic wave resonators on thin film piezoelectric substrates in the quantum regime - data archive

The Archive contains all raw and processed (fitted) data that is used in the manuscript "surface acoustic wave resonators on thin film piezoelectric substrates in the quantum regime" submitted to IOP Materials for quantum technology.

Data sets for heat generation and associated contact temperature during an oblique impact of a deformable particle and a rigid substrate

This dataset contains essential data from the Finite Element Method model predicting heat generation due to friction and plastic deformation during the oblique impact of a deformable particle and a rigid substrate. Part of this data was processed and published in a journal article (<a href="https://doi.org/10.1016/j.powtec.2023.118481">https://doi.org/10.1016/j.powtec.2023.118481</a>). The following is the description of the data files and the associated Figure in the original paper. ‘Heat_Elast_Vt.xlsx’ and ‘Temp_Elast_Vt.xlsx’ data for the evolution of heat and nodal contact temperature, respectively, for varying tangential velocity. Data was used in Figs. 7a and 7b in the associated paper ‘Heat_Vt.xlsx’ and Heat_Vn.xlsx’ data for the evolution of heat for various tangential velocities and normal velocities, respectively. Data was used in Figs. 8a and 8b in the associated paper. ‘Heat_YM.xlsx’ and ‘Temp_YM.xlsx’ data for the evolution of heat and nodal contact temperatures, respectively, for varying Young’s moduli. Data was used in Figs. 9 and 10 in the associated paper. ‘Heat_YS.xlsx’ and ‘Temp_YS.xlsx’ data for the evolution of heat and nodal contact temperatures for varying yield strengths. Data was used in Figs. 11 and 12 in the associated paper. ‘Heat_Den.xlsx’ and ‘Temp_Den.xlsx’ data for heat and nodal contact temperature evolution, respectively, for varying yield strengths. Data was used in Figs. 13 and 14 in the associated paper.  ‘Temp_TC.xlsx’ data for the evolution of nodal contact temperatures for varying thermal conductivities. Data was used in Fig. 15 in the associated paper. ‘Temp_HC.xlsx’ data for the evolution of nodal contact temperatures for varying specific heat capacities. Data was used in Fig. 16 in the associated paper.

opencc-zeroMar 2023View details →

Tsetse flies (Glossina m. morsitans) choose birthing sites guided by substrate cues with no evidence for a role of pheromones

Tsetse flies significantly impact public health and economic development in sub-Saharan African countries by transmitting the fatal disease African trypanosomiasis. Unusually, instead of laying eggs, tsetse birth a single larva that immediately burrows into the soil to pupate. Where the female chooses to larviposit is therefore crucial for offspring survival. Previous laboratory studies suggested that a putative larval pheromone, n-pentadecane, attracts gravid female Glossina morsitans morsitans to appropriate larviposition sites. However, this attraction could not be reproduced in field experiments. Here, we resolve this disparity by designing naturalistic laboratory experiments that closely mimic the physical characteristics found in the wild. We show that gravid G. m. morsitans were neither attracted to the putative pheromone nor, interestingly, to pupae placed in the soil. In contrast, females appear to choose larviposition sites based on environmental substrate cues. We conclude that, among the many cues that likely contribute to larviposition choice in nature, substrate features are a main determinant, while we failed to find evidence of a role of pheromones.

opencc-zeroApr 2023View details →

Data for: Body size and substrate use affect ventral, but not dorsal, brightness evolution in lizards

Substrate properties can affect the thermal balance of organisms, and the colored integument, alongside other factors, may influence heat transfer via differential absorption and reflection. Dark coloration may lead to higher heat absorption and could be advantageous when substrates are cool (and vice versa for bright coloration), but these effects are rarely investigated. Here, we examined the effect of substrate reflectance, specific heat capacity (cp), and body size on the dorso-ventral brightness using 276 samples from 12 species of cordylid lizards distributed across 26 sites in South Africa. We predicted, and found, that bright ventral colors occur more frequently in low cp (i.e. drier, with little energy needed for temperature change) substrates, especially in larger body-sized individuals, possibly to better modulate heat transfer with the surrounding environment. By contrast, dorsal brightness was not associated with body size nor any substrate thermal property, suggesting selection pressures other than thermoregulation. Ancestral estimation and evolutionary rate analyses suggest that ventral brightness rapidly differentiated within the Cordylinae starting 25 Mya, coinciding with an aridification period, further hinting at a thermoregulatory role for ventral colors. Our study indicates that substrate properties can have a direct role in shaping the evolution of ventral brightness in ectotherms.

opencc-by-4.0May 2023View details →

Data sets for temperature rise due to frictional heat generation during a sliding contact between an elastic particle and a rigid substrate

This dataset contains essential data from the Finite Element Method model predicting heat generation due to friction during the sliding contact between an elastic particle and a rigid substrate. Part of this data was processed and presented in an article under review for journal publication. The following is the description of the data files and the associated Figure in the original paper. 'Temp_CoeffFric_01_055.xlsx' data for temperature evolution for the nodes in the contacts and along the particle radius for various friction coefficient values (0.1-0.55). 'Temp_Load_001_01.xlsx' data for temperature evolution for the nodes in the contacts and along the particle radius for various normal load values (0.01-0.1 N). 'Temp_Vel_02_1.xlsx' data for temperature evolution for the nodes in the contacts and along the particle radius for various sliding velocity values (0.2-1 m/s). 'Temp_TC_5_100.xlsx' data for temperature evolution for the nodes in the contacts and along the particle radius for various thermal conductivity values. (i.e. 5-100 W/m K). 'Temp_HC_100_1600.xlsx' data for temperature evolution for the nodes in the contacts and along the particle radius for various thermal conductivity values. (i.e. 100-1600 J/kg K).

opencc-by-4.0Jan 2019View details →

Fig. 1 in Effect of temperature and substrate moisture on group survival of Constrictotermes sp. (Isoptera: Termitidae) under laboratory conditions

Fig. 1. Survival of Constrictotermes sp. in different combinations of temperature and substrate moisture (mL of water/7 g of nest substrate). Different letters in each graphic mean significant difference among treatments of humidity.

FIG. 2 in Bryophyte colonization on the monuments of Champaner Pavagadh - UNESCO World Heritage Site and its association with geological substrates

FIG. 2. — Colonizing liverworts on the selected monuments of Champaner Pavagadh: A, Asterella wallichiana (Lehm. & Lindenb.) Grolle; B, Riccia billardieri Mont. & Nees; C, R. discolor Lehm. & Lindenb.; D, R. gangetica Ahmad.; E, R. grollei Udar.; F, Cyathodium cavernarum Kunze ex Lehm.; G, Plagiochasma appendiculatum Lehm. & Lindenb. and P. microcephalum (Steph.) Steph. Scale bars: 10 mm.

FIG. 1 in Bryophyte colonization on the monuments of Champaner Pavagadh - UNESCO World Heritage Site and its association with geological substrates

FIG. 1. — Glimpses of sites showing biological colonization and deterioration of the monuments of Champaner Pavagadh.

FIG. 6 in Bryophyte colonization on the monuments of Champaner Pavagadh - UNESCO World Heritage Site and its association with geological substrates

FIG. 6. — Spectra of the PXRD of the geological substrate samples from the different sites of Champaner Pavagadh. Peaks number: 1, aluminosilicate; 2, calcite; 3, orthoclase; 4, plagioclase; 5, muscovite; 6, hematite and magnetite.

FIG. 5 in Bryophyte colonization on the monuments of Champaner Pavagadh - UNESCO World Heritage Site and its association with geological substrates

FIG. 5. — Microscopic images of geological substrate thin sections of different sites: A-C, Makai Kothar; D-F, antiquity from the surroundings of Jain Temple; G-I, Navlakha Kothar. Scale bars: 500 μm.

opencc-by-4.0Oct 2023View details →

Evaluation of different settlement substrates for field-based collection of Ostrea edulis. Spatial variation in oyster spat settlement along the Swedish west coast was also monitored.

Aim: Evaluate different types of settlement substrates for field-based collection of Ostrea edulis. Document spatial variation in settlement of oyster spat on coupelle collectors along the Swedish west coast. Different types of substrates (shells of different species and materials with different structures) were placed in the sea and the survival and number of spat attached to the substrates were evaluated. Growth and species identification (O. edulis versus M. gigas) were documented. Data was collected from the Swedish west coast in 2020.

opencc-zeroOct 2023View details →

Data from: Reverse plasticity underlies rapid evolution by clonal selection within populations of fibroblasts propagated on a novel soft substrate

Mechanical properties such as substrate stiffness are a ubiquitous feature of a cell's environment. Many types of animal cells exhibit canonical phenotypic plasticity when grown on substrates of differing stiffness, in vitro and in vivo. Whether such plasticity is a multivariate optimum due to hundreds of millions of years of animal evolution, or instead is a compromise between conflicting selective demands, is unknown. We addressed these questions by means of experimental evolution of populations of mouse fibroblasts propagated for approximately 90 cell generations on soft or stiff substrates. The ancestral cells grow twice as fast on stiff substrate as on soft substrate and exhibit the canonical phenotypic plasticity. Soft-selected lines derived from a genetically diverse ancestral population increased growth rate on soft substrate to the ancestral level on stiff substrate and evolved the same multivariate phenotype. The pattern of plasticity in the soft-selected lines was opposite of the ancestral pattern, suggesting that reverse plasticity underlies the observed rapid evolution. Conversely, growth rate and phenotypes did not change in selected lines derived from clonal cells. Overall, our results suggest that the changes were the result of genetic evolution and not phenotypic plasticity per se. Whole-transcriptome analysis revealed consistent differentiation between ancestral and soft-selected populations, and that both emergent phenotypes and gene expression tended to revert in the soft-selected lines. However, the selected populations appear to have achieved the same phenotypic outcome by means of at least two distinct transcriptional architectures related to mechanotransduction and proliferation.

opencc-by-4.0Sep 2023View details →

Dataset for "Control of Substrate Conformation by Hydrogen Bonding in a Retaining β-Endoglycosidase"

This data set contains files related to the article "Control of Substrate Conformation by Hydrogen Bonding in a Retaining β-Endoglycosidase" by Alba Nin-Hill, Albert Ardèvol, Xevi Biarnés, Antoni Planas and Carme Rovira. ABSTRACTBacterial β-glycosidases are hydrolytic enzymes that depolymerize polysaccharides such as β-cellulose, β-glucans and β-xylans from different sources are used in a myriad of biomedical and industrial applications. It has been shown that a conformational change of the substrate, from a relaxed 4C1 conformation to a distorted 1S3/1,4B conformation of the reactive sugar, is necessary for catalysis. However, the molecular determinants that stabilize the substrate's distortion are poorly understood. Here we use quantum mechanics/molecular mechanics (QM/MM)-based molecular dynamics methods to assess the impact of the interaction between the reactive sugar, i.e. the one at subsite -1, and the catalytic nucleophile (a glutamate) on substrate conformation. We show that the hydrogen bond involving the C2 exocyclic group and the nucleophile controls substrate conformation: its presence preserves sugar distortion, whereas its absence (e.g. in an enzyme mutant) knocks it out. We also show that 2-deoxy-2-fluoro derivatives, widely used to trap the reaction intermediates by X-ray crystallography, reproduce the conformation of the hydrolysable substrate at the experimental conditions. These results highlight the importance of the 2-OH···nucleophile interaction in substrate recognition and catalysis in endo-glycosidases and can inform mutational campaigns aimed to search for more efficient enzymes. DESCRIPTION OF THE DATASETThe data is compressed in a .rar file in where we would find the following folders:<ol><li>Model1_WT</li><li>Model2_2deoxy2F_lowpH</li><li>Model3_2deoxy2F_neutralpH</li><li>Model4_Glu105Gln_lowpH</li><li>Model5_Glu105Gln_neutralpH</li><li>Model6_Glu105Asp_neutralpH</li><li>Model7_Glu105Ala_lowpH</li><li>Model8_Glu105Ile_lowpH</li><li>Model8_Glu105Ile_lowpH</li><li>Model10_Glu105Ile_neutralpH</li><li>scripts</li></ol>Each folder contains the first frame of the production phase of the QM/MM MD simulations in a .pdb format and the representative structures of the whole simulation obtained by clustering in a .nc format.In the scripts folder we can find the scripts used to calculate and analyze the QM/MM MD simulations and a README.txt file with their proper descriptions. More data can be made available upon reasonable request.

ClinicalTrials.gov40/100

A Phase 1 Drug-Drug Interaction Study Between Brigatinib and the CYP3A Substrate, Midazolam, in Participants With ALK-Positive or ROS1-Positive Solid Tumors

ClinicalTrials.gov study NCT03420742. IPD Sharing: YES. Countries: 4. Publications: 1.

controlledIPD-YESFeb 2026View details →

ClinicalTrials.gov40/100

Characterizing the Neural Substrates of Irritability in Women: an Experimental Neuroendocrine Model

ClinicalTrials.gov study NCT04051320. IPD Sharing: YES. Countries: 1. Publications: 98.

controlledIPD-YESFeb 2026View details →

ClinicalTrials.gov40/100

Effect of Pexidartinib on the Way the Body Processes CYP3A4 and CYP2C9 Substrates (Pharmacokinetics)

ClinicalTrials.gov study NCT03291288. IPD Sharing: YES. Countries: 4. Publications: 1.

controlledIPD-YESFeb 2026View details →