Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of orally administered zinc oxide nanoparticles on albino rat thymus and spleen

This study aimed to evaluate the toxicological effects of oral intake of Zinc oxide nanoparticles (ZnO NPs) on the structure of thymus and spleen. Twenty‐four young male Wistar albino rats were assigned into two groups: group I (control) and group II (ZnO NPs treated group). The thymus and spleen were analyzed biochemically, histopathologically and immunohistochemically. After ZnO NPs intake, hematologically, the total leucocytic count was significantly increased while the RBCs and platelets counts and Hb % were significantly decreased. Biochemically, a significant decrease in serum total antioxidant capacity and anti‐inflammatory cytokines including interleukin 4 and 10 (IL‐4 and IL‐10) levels was noted. While a significant increase in splenic and thymic malondialdehyde (MDA) and DNA shearing, as well as the studied proinflammatory cytokines; IL‐1β, tumor necrotic factor (TNF‐α) and interferon (INF‐γ) levels was detected. Notably, we noted upregulation of the immunomodulatory [CD3, CD11b, heme oxygenase (HO‐1)] and the inflammatory [toll‐like receptor 4 and 6 (TLR4 and TLR6)] genes. Histopathologically, degenerative changes were detected in thymus and spleen of ZnO NPs treated group. While the immunohistochemical analysis of the ZnO NPs treated group revealed a decrease in the number of cells expressed positive reactions of anti‐PCNA and an increase in the number of cells expressed positive reaction of anti‐p53 in the thymus and spleen. In conclusion, ZnO NPs induced obvious immunotoxicity in the thymus and spleen, where oxidative/inflammatory pathway may be the potential mechanism underlying this immunotoxicity. © 2017 IUBMB Life, 69(7):528–539, 2017
Powerful Genetic Association Analysis for Common or Rare Variants with High-Dimensional Structured Traits

Genetic association studies often collect a wide range of complex traits, including high-dimensional and structured omics measurements. The complex. Many genetic association studies collect a wide range of complex traits. As these traits may be correlated and share a common genetic mechanism, joint analysis can be statistically more powerful and biologically more meaningful. However, most existing tests for multiple traits cannot be used for high-dimensional and possibly structured traits, such as network-structured transcriptomic pathway expressions. To overcome potential limitations, in this article we propose the dual kernel-based association test (DKAT) for testing the association between multiple traits and multiple genetic variants, both common and rare. In DKAT, two individual kernels are used to describe the phenotypic and genotypic similarity, respectively, between pairwise subjects. Using kernels allows for capturing structure while accommodating dimensionality. Then, the association between traits and genetic variants is summarized by a coefficient which measures the association between two kernel matrices. Finally, DKAT evaluates the hypothesis of nonassociation with an analytical P-value calculation without any computationally expensive resampling procedures. By collapsing information in both traits and genetic variants using kernels, the proposed DKAT is shown to have a correct type-I error rate and higher power than other existing methods in both simulation studies and application to a study of genetic regulation of pathway gene expressions.
CRISPR Knockout of the HuR Gene Causes a Xenograft Lethal Phenotype

Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer-related deaths in the United States, whereas colorectal cancer is the third most common cancer. The RNA-binding protein HuR (ELAVL1) supports a pro-oncogenic network in gastrointestinal (GI) cancer cells through enhanced HuR expression. Using a publically available database, HuR expression levels were determined to be increased in primary PDA and colorectal cancer tumor cohorts as compared with normal pancreas and colon tissues, respectively. CRISPR/Cas9 technology was successfully used to delete the HuR gene in both PDA (MIA PaCa-2 and Hs 766T) and colorectal cancer (HCT116) cell lines. HuR deficiency has a mild phenotype, in vitro, as HuR-deficient MIA PaCa-2 (MIA.HuR-KO(−/−)) cells had increased apoptosis when compared with isogenic wild-type (MIA.HuR-WT(+/+)) cells. Using this isogenic system, mRNAs were identified that specifically bound to HuR and were required for transforming a two-dimensional culture into three dimensional (i.e., organoids). Importantly, HuR-deficient MIA PaCa-2 and Hs 766T cells were unable to engraft tumors in vivo compared with control HuR-proficient cells, demonstrating a unique xenograft lethal phenotype. Although not as a dramatic phenotype, CRISPR knockout HuR HCT116 colon cancer cells (HCT.HuR-KO(−/−)) showed significantly reduced in vivo tumor growth compared with controls (HCT.HuR-WT(+/+)). Finally, HuR deletion affects KRAS activity and controls a subset of pro-oncogenic genes. Implications: The work reported here supports the notion that targeting HuR is a promising therapeutic strategy to treat GI malignancies. Mol Cancer Res; 15(6); 696–707. ©2017 AACR.
Modulation of occluding junctions alters the hematopoietic niche to trigger immune activation

Stem cells are regulated by signals from their microenvironment, or niche. During Drosophila hematopoiesis, a niche regulates prohemocytes to control hemocyte production. Immune challenges activate cell-signalling to initiate the cellular and innate immune response. Specifically, certain immune challenges stimulate the niche to produce signals that induce prohemocyte differentiation. However, the mechanisms that promote prohemocyte differentiation subsequent to immune challenges are poorly understood. Here we show that bacterial infection induces the cellular immune response by modulating occluding-junctions at the hematopoietic niche. Occluding-junctions form a permeability barrier that regulates the accessibility of prohemocytes to niche derived signals. The immune response triggered by infection causes barrier breakdown, altering the prohemocyte microenvironment to induce immune cell production. Moreover, genetically induced barrier ablation provides protection against infection by activating the immune response. Our results reveal a novel role for occluding-junctions in regulating niche-hematopoietic progenitor signalling and link this mechanism to immune cell production following infection.
Use of fire-impacted trees for oriented strandboards

This study evaluates the potential use of currently unexploited burnt timber from prescribed burns and wildfires for oriented strandboard (OSB). The research was performed in two phases: in Phase I, the effect of thermal exposure of timber on OSB properties was evaluated. Jack pine (Pinus banksiana) trees variously damaged by a moderately intense prescribed burn in a northern Wisconsin forest were selected. Four fire-damage levels of wood were defined and processed into series of single-layer OSB. The flakes used in Phase I had all char removed. Mechanical and physical properties were evaluated in accordance with ASTM D 1037. Results showed that OSB engineering performance of all four fire-damage levels were similar, and their mechanical properties met the CSA 0437 requirements. In Phase II, we assessed OSB properties from fire-killed, fire-affected and virgin red pine (Pinus resinosa) trees from a central Wisconsin forest exposed to an intense wildfire. The effect of various thermal exposures and varying amounts of char on OSB performance were evaluated. Phase II findings indicate that fire-damage level and bark amount had significant effects on the board properties. Addition of 20 percent charred bark had an adverse effect on bending strength; however, OSB mechanical properties still met the CSA requirements for all fire levels. Conversely, bark addition up to 20 percent was found to improve dimension stability of boards. This study suggests that burnt timber is a promising alternative bio-feedstock for commercial OSB production.
Neuronal gain modulability is determined by dendritic morphology: A computational optogenetic study

The mechanisms by which the gain of the neuronal input-output function may be modulated have been the subject of much investigation. However, little is known of the role of dendrites in neuronal gain control. New optogenetic experimental paradigms based on spatial profiles or patterns of light stimulation offer the prospect of elucidating many aspects of single cell function, including the role of dendrites in gain control. We thus developed a model to investigate how competing excitatory and inhibitory input within the dendritic arbor alters neuronal gain, incorporating kinetic models of opsins into our modeling to ensure it is experimentally testable. To investigate how different topologies of the neuronal dendritic tree affect the neuron’s input-output characteristics we generate branching geometries which replicate morphological features of most common neurons, but keep the number of branches and overall area of dendrites approximately constant. We found a relationship between a neuron’s gain modulability and its dendritic morphology, with neurons with bipolar dendrites with a moderate degree of branching being most receptive to control of the gain of their input-output relationship. The theory was then tested and confirmed on two examples of realistic neurons: 1) layer V pyramidal cells - confirming their role in neural circuits as a regulator of the gain in the circuit in addition to acting as the primary excitatory neurons, and 2) stellate cells. In addition to providing testable predictions and a novel application of dual-opsins, our model suggests that innervation of all dendritic subdomains is required for full gain modulation, revealing the importance of dendritic targeting in the generation of neuronal gain control and the functions that it subserves. Finally, our study also demonstrates that neurophysiological investigations which use direct current injection into the soma and bypass the dendrites may miss some important neuronal functions, such as gain modulation. Author Summary Gain modulability indicated by dendritic morphology Pyramidal cell-like shapes optimally receptive to modulation All dendritic subdomains required for gain modulation, partial illumination is insufficient Computational optogenetic models improve and refine experimental protocols
Affordance Research in Developmental Robotics: A Survey

Affordances capture the relationships between a robot and the environment in terms of the actions that the robot is able to perform. The notable characteristic of affordance-based perception is that an object is perceived by what it affords (e.g., graspable and rollable), instead of identities (e.g., name, color, and shape). Affordances play an important role in basic robot capabilities such as recognition, planning, and prediction. The key challenges in affordance research are: (1) how to automatically discover the distinctive features that specify an affordance in an online and incremental manner and (2) how to generalize these features to novel environments. This survey provides an entry point for interested researchers, including: (1) a general overview; (2) classification and critical analysis of existing work; (3) discussion of how affordances are useful in developmental robotics; (4) some open questions about how to use the affordance concept; and (5) a few promising research directions.
Selective Impairment of Hippocampal Gamma Oscillations in Connexin-36 Knock-Out Mouse In Vivo

The physiological roles of neuronal gap junctions in the intact brain are not known. The recent generation of the connexin-36 knock-out (Cx36 KO) mouse has offered a unique opportunity to examine this problem. Recent in vitro recordings in Cx36 KO mice suggested that Cx36 gap junction contributes to various oscillatory patterns in the theta (∼5–10 Hz) and gamma (∼30–80 Hz) frequency ranges and affects certain aspects of high-frequency (>100 Hz) patterns. However, the relevance of these pharmacologically induced patterns to the intact brain is not known. We recorded field potentials and unit activity in the CA1 stratum pyramidale of the hippocampus in the behaving wild-type (WT) and Cx36 KO mice. Fast-field “ripple” oscillations (140–200 Hz) were present in both WT and KO mice and did not differ significantly in power, intraepisode frequency, or probability of occurrence. Thus, fast-field oscillations either may not require electrical synapses or may be mediated by a hitherto unknown class of gap junctions. Theta oscillations, recorded during either wheel running or rapid eye movement sleep, were not different either. However, the power in the gamma frequency band and the magnitude of theta-phase modulation of gamma power were significantly decreased in KO mice compared with WT controls during wheel running. This suggests that Cx36 interneuronal gap junctions selectively contribute to gamma oscillations.
Future Self-Continuity Is Associated With Improved Health and Increases Exercise Behavior

To the extent that people feel more continuity between their present and future selves, they are more likely to make decisions with the future self in mind. The current studies examined future self-continuity in the context of health. In Study 1, people reported the extent to which they felt similar and connected to their future self; people with more present-future continuity reported having better subjective health across a variety of measures. In Study 2, people were randomly assigned to write a letter to themselves either three months or 20 years into the future; people for whom continuity with the distant future self was enhanced exercised more in the days following the writing task. These findings suggest that future self-continuity promotes adaptive long-term health behavior, suggesting the promise of interventions enhancing future self-continuity.
Computational design and fabrication of soft pneumatic objects with desired deformations

We present an end-to-end solution for design and fabrication of soft pneumatic objects with desired deformations. Given a 3D object with its rest and deformed target shapes, our method automatically optimizes the chamber structure and material distribution inside the object volume so that the fabricated object can deform to all the target deformed poses with controlled air injection. To this end, our method models the object volume with a set of chambers separated by material shells. Each chamber has individual channels connected to the object surface and thus can be separately controlled with a pneumatic system, while the shell is comprised of base material with an embedded frame structure. A two-step algorithm is developed to compute the geometric layout of the chambers and frame structure as well as the material properties of the frame structure from the input. The design results can be fabricated with 3D printing and deformed by a controlled pneumatic system. We validate and demonstrate the efficacy of our method with soft pneumatic objects that have different shapes and deformation behaviors.
Fibronectin and cytokines increase JNK, ERK, AP-1 activity, and transin gene expression in rat hepatic stellate cells.

Cytokines, growth factors, and alterations in the extracellular matrix composition may play a role in maintaining hepatic stellate cells (HSC) in the activated state that is responsible for hepatic fibrogenesis. However, the signal transduction pathways that are stimulated by these factors in HSC remain to be fully elucidated. Recent evidence indicates that the mitogen-activated protein kinase (MAPK) family, including c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), plays an important role in the cellular response to stress. The aims of this study were to investigate whether fibronectin (FN) or the inflammatory cytokines interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α) activate JNK, ERK, and AP-1 activity in HSC and induce the gene expression of the matrix metalloproteinase transin. Treatment of HSC with FN resulted in an up to 4.5-fold increase in ERK activity and a 2.1-fold increase in JNK activity. IL-1α and TNF-α produced up to a fourfold increase in JNK activity and a twofold increase in ERK activity. We then compared the effects of FN, IL-1α, and TNF-α on AP-1 activity and metalloproteinase mRNA induction. All three compounds increased AP-1 binding and promoter activity, and transin mRNA levels were increased 1.8-fold by FN, 2.2-fold by IL-1α, and 2.8-fold by TNF-α. Therefore, FN and inflammatory cytokines increase MAPK activity, stimulate AP-1 activity, and increase transin gene expression in HSC. Signal transduction pathways involving the MAPK family may play an important role in the regulation of matrix metalloproteinase expression by cytokines and FN in HSC.
Voltage-dependent K+ currents in smooth muscle cells from mouse gallbladder.

The ionic mechanisms associated with the control of gallbladder contractility are incompletely understood. One type of K+ current, the voltage-dependent K+(KV) current, is relatively uncharacterized in gallbladder cells and may contribute to muscular excitability. The main focus of this study was therefore to determine the voltage dependence and pharmacological nature of this K+ current in isolated myocytes from mouse gallbladder, using the patch-clamp technique. Currents through Ca2+-activated K+ channels were minimized by buffering of intracellular Ca2+(20 nM free Ca2+) and by inclusion of 1 mM tetraethylammonium (TEA+) in the bathing solution. With 140 mM symmetrical K+, membrane depolarization increased K+ currents, independent of driving force, as assessed by tail current analysis. Half-maximal activation of K+ currents occurred at ∼1 mV and increased e-fold per 9 mV. Inactivation also increased on depolarization, with a midpoint of -24 mV. Single KV channels were recorded in the cell-attached configuration, exhibiting a single-channel conductance of 4.9 pS. TEA+ at 10 mM reduced KV currents by 36%. At +50 mV, 1 mM and 10 mM 4-aminopyridine inhibited currents by 18% and 35%, respectively, whereas 1 and 10 mM 3,4-diaminopyridine inhibited currents by 11% and 21%, respectively. Quinine inhibited KV currents (at +50 mV, 100 μM and 1 mM quinine inhibited current by 24% and 70%, respectively). In summary, we describe voltage-activated K+ currents from the mouse gallbladder that are likely to contribute to the control of muscular excitability.
Downregulation of voltage-gated K+ channels in rat heart with right ventricular hypertrophy.

The effects of myocardial hypertrophy on mRNA expression levels of voltage-gated K+ channels were investigated using monocrotaline (MCT)-induced pulmonary hypertensive rats. The ratio of right ventricle weight to left ventricle plus septum weight on day 28 was increased significantly compared with control rats [control vs. MCT: 0.27 ± 0.01 vs. 0.58 ± 0.03 ms ( n = 8-13); P < 0.05]. Electrocardiograms showed that QRS duration [control vs. MCT: 26.4 ± 2.6 ms vs. 31.5 ± 5.8 ms ( n = 6); P < 0.05], Q-T interval [control vs. MCT: 100.8 ± 8.9 ms vs. 110.0 ± 4.2 ms ( n = 6); P < 0.05] and corrected Q-T interval [Q-Tc; control vs. MCT: 8.4 ± 0.7 ms vs. 10.2 ± 0.4 ms ( n = 6); P < 0.05] were prolonged significantly on day 28. mRNA levels of Kv1.2, 1.5, 2.1, 4.2, and 4.3 for day 28 assessed by ribonuclease protection assays were decreased significantly from control by 60 ± 10, 76 ± 3, 58 ± 5, 81 ± 5, and 45 ± 12%, respectively ( n = 3; P < 0.005), and Kv1.4 mRNA level for day 28 was unaffected [Kv1.4, control vs. MCT: 1.0 ± 0.28 vs. 0.88 ± 0.44 (arbitrary units) ( n = 3); not significant (NS)]. On the other hand, there was no significant difference between control and MCT rats in mRNA levels of these Kv channels for day 14 [Kv1.2 (control vs. MCT): 1.0 ± 0.25 vs. 0.87 ± 0.18 ( n = 3), NS; Kv1.4: 1.0 ± 0.22 vs. 1.27 ± 0.37 ( n = 3), NS; Kv1.5: 1.0 ± 0.16 vs. 0.91 ± 0.28 ( n = 3), NS; Kv2.1: 1.0 ± 0.26 vs. 0.99 ± 0.25 ( n = 3), NS; Kv4.2: 1.0 ± 0.15 vs. 1.22 ± 0.28 ( n = 3), NS; Kv4.3: 1.0 ± 0.20 vs. 1.21 ± 0.28 ( n= 3), NS]. These findings suggest that altered ventricular repolarization at the advanced stage of hypertrophy may be the result of an inhibition of gene expression of multiple types of voltage-gated K+ channels.
Modulatory Effects of Guarana (Paullinia cupana) on Adipogenesis

Guarana (Paullinia cupana) is a plant originated in Brazil that presents a beneficial effect on body weight control and metabolic alterations. The aim of this study was to evaluate the effects of guarana on genes and miRNAs related to adipogenesis in 3T3L1 cells. The anti-adipogenic effect of guarana was evaluated by Oil Red-O staining. Gene and miRNA expression levels were determined by real time PCR. The Cebpα and β-catenin nuclear translocation were evaluated using immunocytochemistry. Our data indicated that the triglyceride-reducing effect of guarana was dose-dependent from 100 to 300 µg/mL (−12%, −20%, −24% and −40%, respectively, p < 0.0001). An up-regulation of the anti-adipogenic genes Wnt10b, Wnt3a, Wnt1, Gata3 and Dlk1 and a down-regulation of pro-adipogenic genes Cebpα, Pparγ and Creb1 were also observed. Furthermore, guarana repressed mmu-miR-27b-3p, mmu-miR-34b-5p and mmu-miR-760-5p, that contributed for up-regulation of their molecular targets Wnt3a, Wnt1 and Wnt10b. Additionally, cells treated with guarana presented an increase on β-catenin nuclear translocation (p < 0.0018). In summary, our data indicate that guarana has an anti-adipogenic potential due to its ability to modulate miRNAs and genes related to this process. Together our data demonstrate the important role of guarana as a putative therapeutic agent.
Three-dimensional finite-deformation multiscale modeling of elasto -viscoplastic open -cell foams in the dynamic regime

OF THE DISSERTATION Three-Dimensional Finite-Deformation Multiscale Modeling of Elasto-Viscoplastic Open-Cell Foams in the Dynamic Regime by Pedro A. Romero Dissertation Director: Dr. Alberto M. Cuitiño Cellular materials such as metallic and polymeric open-cell foams resemble a labyrinth of interconnected struts surrounded by air-filled voids however a closer inspection reveals a periodicity where a particular unit cell is repeated throughout a lattice inside a matrix of air. Depending on the loading rate, the specifics of the cellular topology and the material properties of the solid phase, the different stages of deformation can involve elasticity, plasticity, fracture, viscoelasticiy, thermoelasticity, strain rate effects, density (microinertia) etc. This dissertation contributes an approach for modeling dynamically loaded open-cell foam materials where the structure is mimicked with the replication of a periodic unit cell composed of a four ligament tetrahedron inside a dual tetrakaidecahedron volume element. Formulation of the Lagrangian for a representative unit cell comprising an imposed macroscopic deformation and enforcement of the principle of minimum action for dissipative systems results in a relation between the globally applied macroscopic deformation and the motion of the internal unit cell vertex, which uniquely defines the kinematic state of each cell and the effective stress state. By maintaining the history of local non-affine motion along with the global affine