Miracle-dz/UniFAR-FTUs huggingface dataset:
Hepatic Proteome Sensitivity in Rainbow Trout after Chronically Exposed to a Human Pharmaceutical Verapamil*

Verapamil (VRP), a cardiovascular pharmaceutical widely distributed and persistent in the aquatic environment, has potential toxicity to fish and other aquatic organisms. However, the molecular mechanisms that lead to these toxic effects are not well known. In the present study, proteomic analysis has been performed to investigate the protein patterns that are differentially expressed in liver of rainbow trout exposed to sublethal concentrations of VRP (0.5, 27.0, and 270 μg/liter) for 42 days. Two-dimensional electrophoresis coupled with MALDI-TOF/TOF mass spectrometry was employed to detect and identify the protein profiles. The analysis revealed that the expression of six hepatic acidic proteins were markedly altered in the treatment groups compared with the control group; three proteins especially were significantly down-regulated in fish exposed to VRP at environmental related concentration (0.5 μg/liter). These results suggested that the VRP induce mechanisms against oxidative stress (glucose-regulated protein 78 and 94 and protein disulfide-isomerase A3) and adaptive changes in ion transference regulation (calreticulin, hyperosmotic glycine-rich protein). Furthermore, for the first time, protein Canopy-1 was found to be significantly down-regulated in fish by chronic exposure to VRP at environmental related levels. Overall, our work supports that fish hepatic proteomics analysis serves as an in vivo model for monitoring the residual pharmaceuticals in aquatic environment and can provide valuable insight into the molecular events in VRP-induced toxicity in fish and other organisms.
Computed tomography‐based finite element analysis predicts failure loads and fracture patterns for vertebral sections

Computed tomography‐based finite element analysis represents a powerful research tool for investigating the mechanics of skeletal fractures. To provide evidence that this technique can be used to predict failure loads and fracture patterns for bone structures, we compared the observed and predicted failure behaviors of 18 midsagittal sections. 10 mm thick, cut from human vertebral bodies. The specimens were scanned by computed tomography, and finite element models were generated with use of empirically determined density‐property relations to assign element‐specific material properties. The specimens were loaded to failure in uniaxial compression, and the models were analyzed under matching conditions. The models provided predictions of yield load that were strongly correlated with experimentally measured values (r2 > 0.86) and were typically within 25% of measured values. Predicted stiffness values were moderately correlated with measured values, but large absolute differences existed between them. Comparisons between regions of observed fracture and of high predicted strain indicated that strain was an accurate indicator of the pattern of local fracture in more than two‐thirds of the bone specimens. In addition, strain contour plots provided better indicators of local fracture than did stress plots in these heterogeneous bone structures. We conclude that computed tomography‐based finite element analysis can be used successfully to predict both global and local failure behavior of simplified skeletal structures.
In Vitro Treatment of Human Monocytes/Macrophages with Myristoylated Recombinant Nef of Human Immunodeficiency Virus Type 1 Leads to the Activation of Mitogen-Activated Protein Kinases, IκB Kinases, and Interferon Regulatory Factor 3 and to the Release of Beta Interferon

ABSTRACT The viral protein Nef is a virulence factor that plays multiple roles during the early and late phases of human immunodeficiency virus (HIV) replication. Nef regulates the cell surface expression of critical proteins (including down-regulation of CD4 and major histocompatibility complex class I), T-cell receptor signaling, and apoptosis, inducing proapoptotic effects in uninfected bystander cells and antiapoptotic effects in infected cells. It has been proposed that Nef intersects the CD40 ligand signaling pathway in macrophages, leading to modification in the pattern of secreted factors that appear able to recruit and activate T lymphocytes, rendering them susceptible to HIV infection. There is also increasing evidence that in vitro cell treatment with Nef induces signaling effects. Exogenous Nef treatment is able to induce apoptosis in uninfected T cells, maturation in dendritic cells, and suppression of CD40-dependent immunoglobulin class switching in B cells. Previously, we reported that Nef treatment of primary human monocyte-derived macrophages (MDMs) induces a cycloheximide-independent activation of NF-κB and the synthesis and secretion of a set of chemokines/cytokines that activate STAT1 and STAT3. Here, we show that Nef treatment is capable of hijacking cellular signaling pathways, inducing a very rapid regulatory response in MDMs that is characterized by the rapid and transient phosphorylation of the α and β subunits of the IκB kinase complex and of JNK, ERK1/2, and p38 mitogen-activated protein kinase family members. In addition, we have observed the activation of interferon regulatory factor 3, leading to the synthesis of beta interferon mRNA and protein, which in turn induces STAT2 phosphorylation. All of these effects require Nef myristoylation.
Effects of ligand binding upon flexibility of proteins

Binding of a ligand on a protein changes the flexibility of certain parts of the protein, which directly affects its function. These changes are not the same at each point, some parts become more flexible and some others become stiffer. Here, an equation is derived that gives the stiffness map for proteins. The model is based on correlations of fluctuations of pairs of points in proteins, which may be evaluated at different levels of refinement, ranging from all atom molecular dynamics to general elastic network models, including the simplest case of isotropic Gaussian Network Model. The latter is used, as an example, to evaluate the changes of stiffness upon dimerization of ACK1. Proteins 2015; 83:805–808. © 2015 Wiley Periodicals, Inc.
An Analysis of the Bacterial Flora Found in the External Auditory Canals of Microtia Patients: Results and Clinical Applications

During the process of auricular reconstruction in cases of microtia patients with external auditory canals (EAC), bacterial contamination from the EAC can cause cartilage infection. In this article, we retrospectively analyzed the data on bacterial flora present in the EAC of these patients. Preoperatively, in 91 microtia patients, culture samples were obtained, and isolates were tested for in vitro susceptibility to antibiotics. One hundred volunteers with no ear abnormalities were also evaluated as part of the control group. Seventy-nine specimens in 91 microtia patients showed growth of bacteria (86.8%): a total of 97 organisms were isolated. Dominating bacteria were of the staphylococci species (85.6%). Fourteen Staphylococcus isolates were resistant to methicillin. The percentage of microtia patients showing a presence of methicillin-resistant staphylococci isolates (15%) was significantly higher than the percentage in the “normal” volunteer group showing a presence of methicillin-resistant staphylococci isolates (2%; P = 0.0009). To decrease the complications that occurred due to cartilage infection during auricular reconstruction in the cases of microtia with EAC, we suggest that bacterial floras of the EAC be routinely examined and the patients be treated with appropriate antibiotics preoperatively.
CQM: Coverage-Constrained Quality Maximization in Crowdsourcing Test

Mobile app testing is challenging since each test needs to be executed in a variety of operating contexts including heterogeneous devices, various wireless networks, and different locations. Crowdsourcing enables a mobile app testing to be distributed as a crowdsourced task to leverage the crowd in a community. However, a high test quality and expected test context coverage are difficult to achieve in crowdsourcing test. Upon distributing a test task, mobile app providers can neither know who will participate and submit a high-qualified test report nor predict whether all expected test contexts can be covered during the test. To address this problem, we put forward a novel research problem called Coverage-constrained Quality Maximization (CQM) for crowdsourcing test. Given a mobile app test task, our objective is to discover and recommend a set of potential workers from available crowd workers such that they can accomplish the task achieving expected test context coverage and the possible highest test quality. We prove that the CQM problem is NP-Complete and then introduce two efficient greedy algorithms. Based on a real dataset of the largest Chinese crowdsourcing test platform, our evaluation shows that the proposed algorithms are effective and efficient, and can be potentially used as online services in practice.
Physicochemical characterization and antibacterial activity of Rajata Bhasma and silver nanoparticle

Introduction: Bhasma, an Ayurvedic metallo-mineral preparation, is claimed to be biologically produced nanoparticles. Rajata (silver) is a noble metal known for its antimicrobial activity. Rajata Bhasma (RB) is expected to be composed of nanoparticles. With all these facts in place, this study was conducted to evaluate RB for the presence of silver nanoparticle (SNP) and its antimicrobial effect. Aim: The aim of this study is to analyze the physicochemical characterization, antibacterial activity of RB, and SNP. Materials and Methods: RB was commercially ordered and SNP was prepared by Turkevich method. Characterization of RB was carried out by scanning electron microscopy (SEM) and inductively coupled plasma-atomic emission spectroscopy (ICP-AES). SNP was characterized by ultraviolet (UV)-visible spectroscopy, transmission electron microscopy (TEM), and ICP-AES. Antibacterial activity of RB and SNP was carried out by well-diffusion method. Results: Analysis of RB by SEM revealed particles in range from 10 to 60 nm. UV-visible spectrum of the aqueous medium containing SNPs showed absorption peak at around 423 nm. The TEM analysis showed that SNP was spherical in the range of 5–50 nm and uniformly distributed without significant agglomeration. The content of silver in RB measured with ICP-AES was found to be 70.56% whereas in case of SNP was 65.23%. Staphylococcus aureus was found to be sensitive to both RB and SNP. Escherichia coli, Pseudomonas aeruginosa, and Enterococcus faecalis were found to be resistant to RB as well as SNP. Conclusion: The current study shows that RB does have silver particles in the size of nanometers and also has mild antibacterial activity.
Nonoperatively treated isolated posterior cruciate ligament injuries

To evaluate the theory that isolated posterior cruciate ligament injuries do well when treated nonoperatively, we reviewed 40 patients (mean age, 33 years at fol lowup ; average interval from injury, 6 years) who com pleted a modified Noyes knee questionnaire and were reevaluated by physical examination, radiographs, and isokinetic testing. Thirty of the injuries to the posterior cruciate ligament were sports-related. On the question naire, 65% of the patients revealed that their activity level after injury was limited and 49% stated that the involved knee had not recovered fully despite rehabili tation. Ninety percent complained of knee pain with activity and 43% complained of problems with walking. The longer the interval between injury and this followup, the lower the knee questionnaire score and the greater the radiographic degenerative changes. The patients as a group exhibited excellent muscular strength with a mean isokinetic score of 99% of the contralateral extremity. There was no correlation between isokinetic testing and knee questionnaire score. Patients with greater posterior laxity, as measured by the posterior drawer examination, appeared to have greater subjec tive complaints. Our study suggests that patients with isolated posterior cruciate ligament injuries treated non operatively may maintain excellent muscle strength, but significant symptoms and degenerative changes in crease with increasing interval from injury.
MEF 2 : a transcriptional target for signaling pathways controlling skeletal muscle growth and differentiation

Skeletal muscle development involves a multistep pathway in which mesodermal precursor cells are selected, in response to inductive cues, to form myoblasts that later withdraw from the cell cycle and differentiate. The transcriptional circuitry controlling muscle differentiation is intimately linked to the cell cycle machinery, such that muscle differentiation genes do not become transcribed until myoblasts have exited the cell cycle. Members of the MyoD and MEF2 families of transcription factors associate combinatorially to control myoblast specification, differentiation and proliferation. Recent studies have revealed multiple signaling systems that stimulate and inhibit myogenesis by altering MEF2 phosphorylation and its association with other transcriptional cofactors.
Efficient mesoporous anatase-brookite TiO2 photocatalysts for degradation of ibuprofen

Mesoporous anatase-brookite heterojunction TiO2 photocatalysts with tunable brookite/anatase ratios controlled by glycine assistant were successfully synthesized by facile hydrothermal process. In addition, pure brookite phase was prepared in the absence of glycine. The obtained TiO2 catalysts have been characterized by X-ray diffraction, Brunauer-Emmett-Teller analysis, transmission electron microscope and field emission-scanning electron microscopy. The X-ray diffraction revealed the formation of brookite-phase either in pure form in the absence of glycine or in mixing with anatase in the presence of glycine. The field emission-scanning electron microscopy micrograph of pure brookite indicated the formation of spindle-like structures with particle size ~ 25 nm. The transmission electron microscope image of the optimum sample indicated the formation of small quasi-spherical particles and rod-like particles. N2 isotherm measurements confirmed that anatase/brookite TiO2 materials have mesoporous structure. The photocatalytic degradation of ibuprofen with low concentration was investigated using these novel TiO2 materials under UV irradiation light for water treatment. The anatase/brookite TiO2 samples showed a superior photocatalytic activity compared to pure brookite TiO2 sample. Sample containing 74.4% anatase/25.6 brookite displayed the highest photocatalytic activity for ibuprofen degradation (98.9 %) under UV light for 120 min due to the synergistic effect between anatase and brookite phases, high surface area (72.4 m2 g-1) and mesoporous structure.
Protein Kinase A-dependent Phosphorylation of Rap1 Regulates Its Membrane Localization and Cell Migration*

Background: The small G protein Rap1 is phosphorylated within its carboxyl terminus by the cAMP-dependent protein kinase PKA. Results: This phosphorylation removes Rap1 from the plasma membrane to limit Rap1 signaling. Conclusion: Rap1 phosphorylation switches Rap1 off the membrane and terminates its activation. Significance: Carboxyl-terminal phosphorylation may be common among small G proteins to regulate GTP/GDP cycling and downstream signaling. The small G protein Rap1 can mediate “inside-out signaling” by recruiting effectors to the plasma membrane that signal to pathways involved in cell adhesion and cell migration. This action relies on the membrane association of Rap1, which is dictated by post-translational prenylation as well as by a stretch of basic residues within its carboxyl terminus. One feature of this stretch of acidic residues is that it lies adjacent to a functional phosphorylation site for the cAMP-dependent protein kinase PKA. This phosphorylation has two effects on Rap1 action. One, it decreases the level of Rap1 activity as measured by GTP loading and the coupling of Rap1 to RapL, a Rap1 effector that couples Rap1 GTP loading to integrin activation. Two, it destabilizes the membrane localization of Rap1, promoting its translocation into the cytoplasm. These two actions, decreased GTP loading and decreased membrane localization, are related, as the translocation of Rap1-GTP into the cytoplasm is associated with its increased GTP hydrolysis and inactivation. The consequences of this phosphorylation in Rap1-dependent cell adhesion and cell migration were also examined. Active Rap1 mutants that lack this phosphorylation site had a minimal effect on cell adhesion but strongly reduced cell migration, when compared with an active Rap1 mutant that retained the phosphorylation site. This suggests that optimal cell migration is associated with cycles of Rap1 activation, membrane egress, and inactivation, and requires the regulated phosphorylation of Rap1 by PKA.
Micro-lipid-droplet encapsulation of Bacillus thuringiensis subsp. israelensis delta-endotoxin for control of mosquito larvae

The crystal delta-endotoxin of Bacillus thuringiensis subsp. israelensis is less toxic to larvae of Anopheles freeborni than to larvae of Aedes aegypti. However, when solubilized crystal was used, larvae from both species showed similar sensitivities. This effect presumably was due to the differences in feeding behavior between the two mosquito larvae when crystal preparations are used. A procedure is described whereby both crystal and solubilized B. thuringiensis subsp. israelensis toxin were emulsified with Freund incomplete adjuvant, with retention of toxicity. The use of Freund incomplete adjuvant also allowed one to assay the solubilized toxin at a low nanogram level. Furthermore, coating the toxin with lipophilic material altered the buoyancy of the toxin and reversed the sensitivities of the two mosquito larvae toward the B. thuringiensis subsp. israelensis toxin. This difference in buoyancy was determined by using an enzyme-linked immunosorbent assay that was specific for the toxic peptides. These data indicate that economically feasible buoyant formulations for the B. thuringiensis subsp. israelensis crystal can be developed.
Beneficial Outcomes of Sleeve Gastrectomy in a Morbidly Obese Patient With Bardet-Biedl Syndrome

Context: Severe obesity is one of the major features of Bardet-Biedl syndrome (BBS) and causes reduced life expectancy. Bariatric surgery is an effective treatment of morbid obesity. Data on the effect of bariatric surgery for monogenic obesity is essentially lacking. We present the clinical and metabolic 3-year follow-up of sleeve gastrectomy in a BBS patient. Case Description: A 37-year-old obese woman with BBS (body mass index, 40 kg/m2) was referred to our clinic for uncontrolled diabetes, dyslipidemia, hypertension, and nonalcoholic fatty liver disease (NAFLD). After sleeve gastrectomy, progressive weight loss was observed, with a 32% total weight loss at 3-year follow-up. Glycemic control and NAFLD improved significantly. Blood pressure normalized, and treatment was discontinued 3 months after surgery. Conclusions: Laparoscopic sleeve gastrectomy can be a safe and effective treatment of morbid BBS-related obesity in adult patients. Significant and sustained weight loss leads to the improvement of several obesity-related comorbidities such as diabetes, hypertension, and NAFLD, as in polygenic obesity. Further data are needed to confirm the long-term efficacy and safety of bariatric surgery in BBS.
Safety and dose relationship of recombinant human activated protein C for coagulopathy in severe sepsis

Objectives To assess the safety and effect on coagulopathy of a range of doses of recombinant human activated protein C (rhAPC). To determine an effective dose and duration of rhAPC for use in future clinical trials. Design Double-blind, randomized, placebo-controlled, multicenter, dose-ranging (sequential), phase II clinical trial. Setting Forty community or academic medical institutions in United States and Canada. Patients One hundred thirty-one adult patients with severe sepsis. Interventions Intravenous infusion of rhAPC (12, 18, 24, or 30 &mgr;g/kg/hr) or placebo for 48 or 96 hrs. Measurements and Main Results No significant differences in incidence of serious bleeding events (4% rhAPC, 5% placebo, p > .999) or incidence of serious adverse events (39% rhAPC, 46% placebo, p = 0.422) between rhAPC- and placebo-treated patients were observed. One of 53 rhAPC-treated patients with suitable immunogenicity samples had a low level, transient, non-neutralizing anti-APC antibody response not associated with any clinical adverse event. Significant dose-dependent decreases in both D-dimer (p <0.001) and end of infusion interleukin 6 levels (p = .021) were demonstrated. No statistically significant effects on fibrinogen or platelet counts were observed. A nonstatistically significant 15% relative risk reduction in 28-day all-cause mortality was observed between rhAPC- and placebo-treated patients. Conclusions rhAPC was safe and well-tolerated and demonstrated a dose-dependent reduction in D-dimer and interleukin 6 levels relative to placebo. The dose of 24 &mgr;g/kg/hr for 96 hrs was selected for use in future clinical studies.
A retrospective analysis of mandibular bone height changes associated with 81 screw-retained implant-supported prostheses with distal cantilevers: a long-term follow-up analysis.

PURPOSE The aims of this study were (1) to evaluate long-term changes in bone height beneath mandibular screw-retained implant-supported prostheses with distal cantilevers and (2) to determine whether the reversal of residual ridge resorption in the posterior mandible is temporary or continues over the long term. MATERIALS AND METHODS Panoramic radiographs, obtained at surgery and at two follow-up visits, of 81 patients rehabilitated with mandibular screw-retained implant-supported prostheses with distal cantilevers supported by four, five, or six implants were followed for 5 to 19 years (overall mean follow-up, 9.00 years. Changes and trends in bone height adjacent to the most distal implant were evaluated between each follow up visit as well as from time of surgery (baseline) to the final visit using two-way analysis of variance, a two-sample t test, and piecewise linear regression. RESULTS Average bone height distal to the distal most implant at placement was 10.34 ± 6.87 mm. From baseline to the first follow-up exam, a mean bone gain of 0.68 mm was noticed, and a mean gain of 0.26 mm was observed from baseline to the second follow-up exam. A statistically significant bone gain (0.92 mm) was noticed in women (n = 49) between the first and second exams, compared to 0.33 mm in men (n = 32). Individuals experienced both bone gain and loss during the study, with an overall gain. Patients with lower initial bone height experienced greater growth, but this was not statistically significant. CONCLUSION Bone growth is associated with mandibular screw-retained implant-supported prostheses with distal cantilevers, and both bone loss and bone growth may occur in the same patient over time. Within the diverse population of this study, women experienced 2.5 times more gain in bone height than men. No correlation could be established between initial bone height and overall bone height changes.