Miracle-dz/UniFAR-FTUs huggingface dataset:
mTORC2 Regulates Mechanically Induced Cytoskeletal Reorganization and Lineage Selection in Marrow‐Derived Mesenchymal Stem Cells

The cell cytoskeleton interprets and responds to physical cues from the microenvironment. Applying mechanical force to mesenchymal stem cells induces formation of a stiffer cytoskeleton, which biases against adipogenic differentiation and toward osteoblastogenesis. mTORC2, the mTOR complex defined by its binding partner rictor, is implicated in resting cytoskeletal architecture and is activated by mechanical force. We asked if mTORC2 played a role in mechanical adaptation of the cytoskeleton. We found that during bi‐axial strain‐induced cytoskeletal restructuring, mTORC2 and Akt colocalize with newly assembled focal adhesions (FA). Disrupting the function of mTORC2, or that of its downstream substrate Akt, prevented mechanically induced F‐actin stress fiber development. mTORC2 becomes associated with vinculin during strain, and knockdown of vinculin prevents mTORC2 activation. In contrast, mTORC2 is not recruited to the FA complex during its activation by insulin, nor does insulin alter cytoskeletal structure. Further, when rictor was knocked down, the ability of mesenchymal stem cells (MSC) to enter the osteoblastic lineage was reduced, and when cultured in adipogenic medium, rictor‐deficient MSC showed accelerated adipogenesis. This indicated that cytoskeletal remodeling promotes osteogenesis over adipogenesis. In sum, our data show that mTORC2 is involved in stem cell responses to biophysical stimuli, regulating both signaling and cytoskeletal reorganization. As such, mechanical activation of mTORC2 signaling participates in mesenchymal stem cell lineage selection, preventing adipogenesis by preserving β‐catenin and stimulating osteogenesis by generating a stiffer cytoskeleton. © 2014 American Society for Bone and Mineral Research.
Effect of Estradiol on Gene Expression Profile in Cynomolgus Macaque Liver: Implications for Drug-Metabolizing Enzymes

Estrogen regulation of gene expression is essential for physiological function of estrogen-responsive tissues, such as mammary glands, ovaries, and the uterus. In the liver, estrogen is responsible for sex-dependent gene expression of drug-metabolizing enzymes in rodents. However, the influence of estrogen on hepatic gene expression has not been fully investigated in primates, including human. Macaque, including cynomolgus macaque, is an important species for comparative studies aimed at understanding human physiology due to its evolutionary closeness to human. To identify estrogen-responsive genes in primate liver, therefore, hepatic gene expression was compared, by microarray analysis, in ovariectomized cynomolgus macaques treated with estradiol or solvent (control). The analysis identified 98 estradiol-responsive genes; 47 and 51 were up- and down-regulated by estradiol, respectively (≥2.0-fold, P < 0.05). Expression of drug-metabolizing enzyme genes was also influenced by estradiol treatment; estradiol enhanced expression of GSTM5 (3.8-fold, P < 0.05) and CYP3A8(4) (2.7-fold, P < 0.01), but lowered expression of CYP4F12 (2.2-fold, P < 0.01), as verified by quantitative polymerase chain reaction. In particular, CYP3A8(4), orthologous to human CYP3A4, is an essential drug-metabolizing enzyme in cynomolgus macaque liver. These results suggest that expression of hepatic genes, including drug-metabolizing enzyme genes, is at least partly regulated by estradiol in cynomolgus macaque.
The Role of Reciprocity in Verbally Persuasive Robots

The current research examines the persuasive effects of reciprocity in the context of human-robot interaction. This is an important theoretical and practical extension of persuasive robotics by testing (1) if robots can utilize verbal requests and (2) if robots can utilize persuasive mechanisms (e.g., reciprocity) to gain human compliance. Participants played a trivia game with a robot teammate. The ostensibly autonomous robot helped (or failed to help) the participants by providing the correct (vs. incorrect) trivia answers. Then, the robot directly asked participants to complete a 15-minute task for pattern recognition. Compared to no help, results showed that a robot's prior helping behavior significantly increased the likelihood of compliance (60 percent vs. 33 percent). Interestingly, participants' evaluations toward the robot (i.e., competence, warmth, and trustworthiness) did not predict compliance. These results also provided an insightful comparison showing that participants complied at similar rates with the robot and with computer agents. This result documents a clear empirically powerful potential for the role of verbal messages in persuasive robotics.
Anorganic bovine bone (ABB) vs. autologous bone (AB) plus ABB in maxillary sinus grafting. A prospective non-randomized clinical and histomorphometrical trial.

OBJECTIVES This investigation focused on histological characteristics and 5-year implant survival after sinus floor augmentation with anorganic bovine bone (ABB, Bio-Oss) and ABB plus autologous bone (AB) with a ratio of 1/1. MATERIAL AND METHODS Nineteen consecutive patients with bony atrophy of the posterior edentulous maxilla and a vertical bone height ≤4 mm were prospectively included in this study. In the first surgical stage, the maxillary sinus was non-randomized either augmented with ABB alone (n = 12) or a 1/1 mixture of ABB and AB (n = 7). After a mean healing period of 167 days, biopsies were harvested in the region of the grafted sinus with a trephine burr and implants were placed simultaneously, ABB n = 18 and ABB + AB n = 12. The samples were microradiographically and histomorphometrically analyzed judging the newly formed bone (bone volume, BV), residual bone substitute material volume (BSMV), and intertrabecular volume (soft tissue volume, ITV) in the region of the augmented maxillary sinus. Implant survival was retrospectively evaluated from patient's records. RESULTS No significant difference in residual bone substitute material (BSMV) in the ABB group (31.21 ± 7.74%) and the group with the mixture of ABB and AB (28.41 ± 8.43%) was histomorphologically determined. Concerning the de novo bone formation, also both groups showed statistically insignificant outcomes; ABB 26.02 ± 5.23% and ABB + AB 27.50 ± 6.31%. In all cases, implants were installed in the augmented sites with sufficient primary stability. After a mean time in function of 5 years and 2 months, implant survival was 93.75% in the ABB and 92.86% in the ABB + AB group with no statistically significant differences. CONCLUSION The usage of ABB plus AB to a 1/1 ratio leads to an amount of newly formed bone comparable with the solitary use of ABB after grafting of the maxillary sinus. Considering that ABB is a non-resorbable bone substitute, it can be hypothesized that this leads to stable bone over time and long-term implant success. Importantly, in the sole use of ABB, bone grafting and therefore donor site morbidities can be avoided.
Excessive zinc intake elevates systemic blood pressure levels in normotensive rats – potential role of superoxide-induced oxidative stress

Objectives The present study was designed to examine whether or not excessive Zn intake affects systemic blood pressure (BP) levels in a normotensive state. Methods Systolic BP (SBP) and mean arterial pressure (MAP) before and after administration of the nitric oxide synthase (NOS) inhibitor, Nω-nitro-L-arginine methyl ester (l-NAME) or the exogenous superoxide scavenger, tempol and the activity of the endogenous superoxide scavenger, Cu/Zn-superoxide dismutase (SOD) and levels of endothelial type (e)NOS mRNA and protein in the thoracic aorta were analyzed in male Sprague–Dawley rats fed a standard diet containing 0.005% Zn or a high Zn diet containing 0.5% Zn for 8 weeks. Results SBP and MAP levels observed at the end of dietary conditioning were significantly elevated in rats fed a high Zn diet relative to rats fed a standard diet. Administration of l-NAME caused an increase in MAP levels in rats fed a standard and a high Zn diet, demonstrating the involvement of the vasodilator, nitric oxide (NO) in the regulation of systemic BP in the two groups of rats. However, the expression of eNOS mRNA and protein in the thoracic aorta was not significantly different between rats fed a standard and a high Zn diet. On the other hand, administration of tempol led to a decrease in MAP levels in rats fed a standard and a high Zn diet, indicating the participation of the oxygen free radical, superoxide in the modification of systemic BP in the two groups of rats. As reported recently, the mechanism involved is due likely to a decrease in the action of the vasodilator, NO through the formation of peroxynitrite based on the non-enzymatic reaction of superoxide and NO. In addition, tempol treatment dramatically restored MAP levels in rats fed a high Zn diet to levels comparable with those observed in rats fed a standard diet, indicating that an elevation in systemic BP levels seen in rats fed a high Zn versus a standard diet is presumably brought by a reduction in the action of the vasodilator, NO resulting from an increase in the action of superoxide. The activity of Cu/Zn-SOD in the thoracic aorta was significantly reduced in rats fed a high Zn diet relative to rats fed a standard diet, appearing to at least in part, play a role in an increase in the action of superoxide in the vessel wall of rats fed a high Zn diet. Conclusions Excessive Zn intake may be a factor to elevate systemic BP levels in a normotensive state presumably through the oxidative stress caused by superoxide.
Conformational Switching in Ezrin Regulates Morphological and Cytoskeletal Changes Required for B Cell Chemotaxis

B cell chemotaxis occurs in response to specific chemokine gradients and is critical for homeostasis and immune response. The molecular regulation of B cell membrane–actin interactions during migration is poorly understood. In this study, we report a role for ezrin, a member of the membrane-cytoskeleton cross-linking ezrin-radixin-moesin proteins, in the regulation of the earliest steps of B cell polarization and chemotaxis. We visualized chemokine-induced changes in murine B cell morphology using scanning electron microscopy and spatiotemporal dynamics of ezrin in B cells using epifluorescence and total internal reflection microscopy. Upon chemokine stimulation, ezrin is transiently dephosphorylated to assume an inactive conformation and localizes to the lamellipodia. B cells expressing a phosphomimetic conformationally active mutant of ezrin or those in which ezrin dephosphorylation was pharmacologically inhibited displayed impaired microvillar dynamics, morphological polarization, and chemotaxis. Our data suggest a 2-fold involvement of ezrin in B cell migration, whereby it first undergoes chemokine-induced dephosphorylation to facilitate membrane flexibility, followed by relocalization to the actin-rich lamellipodia for dynamic forward protrusion of the cells.
Temperature, Humidity, and Ultraviolet B Radiation Predict Community Respiratory Syncytial Virus Activity

To obtain knowledge of how meteorological conditions affect community epidemics of respiratory syncytial virus (RSV) infection, RSV activity was recorded year-round in 9 cities that differ markedly in geographic location and climate. Local weather conditions were correlated with weekly or monthly RSV cases. Similar reports from other areas varying in climate were also reviewed. Results demonstrated that for all sites combined, weekly RSV activity was related to temperature in a bimodal fashion, with peaks of activity at temperatures more than 24–30°C and at 2–6°C. RSV activity also was greatest at 45-65% relative humidity. RSV activity was inversely related to ultraviolet B (UVB) radiance at 3 sites where this could be analyzed; the fourth site had minimal amounts of annual UVB radiance. At sites with persistently warm temperatures and high humidity, RSV activity was continuous throughout the year, peaking in summer and early autumn. In temperate climates, RSV activity was maximal during winter, correlating with lower temperatures. In areas where temperatures remained cold throughout the year, RSV activity again became nearly continuous. These data led us to conclude that community activity of RSV is substantial when both ambient temperatures and absolute humidity are very high, perhaps reflecting greater stability of RSV in aerosols; transmission of RSV in cooler climates is inversely related to temperature, possibly as a result of increased stability of the virus in secretions in the colder environment; and UVB radiation may inactivate the virus in the environment or influence susceptibility to RSV by altering host resistance.
Single-layer differentially-fed circularly polarized aperture antenna for 60 GHz applications

This paper presents a new differentially-fed aperture antenna for circularly polarized (CP) radiation. The proposed antenna is simple in structure and is constructed on only a single layer laminate using standard printed-circuit-board (PCB) technology. The antenna is fed using substrate integrated waveguide (SIW), which features low transmission loss and high efficiency. Circular polarization is realized using a dual loop-like strips formation with travelling wave distribution as the radiating element. A cavity that is formed by the SIW metalized vias is adopted to offer favorable unidirectional radiation and higher gain. Measurement results of the antenna show a 3-dB axial ratio (AR) bandwidth of 16.3% (56.5-66.5 GHz), which is within its -10-dB impedance bandwidth. Meanwhile, the right-handed CP (RHCP) gain is stable throughout the operating bandwidth with a peak gain of 12.4 dBi. The proposed antenna is a promising candidate for 60 GHz applications due to its merits of wideband, high efficiency, simple structure, low cost, and easy integration with differential circuits.
Ability of Shiga Toxin-Producing Escherichia coli and Salmonella spp. To Survive in a Desiccation Model System and in Dry Foods

ABSTRACT In order to determine desiccation tolerances of bacterial strains, the survival of 58 diarrheagenic strains (18 salmonellae, 35 Shiga toxin-producing Escherichia coli [STEC], and 5 shigellae) and of 15 nonpathogenic E. coli strains was determined after drying at 35°C for 24 h in paper disks. At an inoculum level of 107 CFU/disk, most of the salmonellae (14/18) and the STEC strains (31/35) survived with a population of 103 to 104 CFU/disk, whereas all of the shigellae (5/5) and the majority of the nonpathogenic E. coli strains (9/15) did not survive (the population was decreased to less than the detection limit of 102 CFU/disk). After 22 to 24 months of subsequent storage at 4°C, all of the selected salmonellae (4/4) and most of the selected STEC strains (12/15) survived, keeping the original populations (103 to 104 CFU/disk). In contrast to the case for storage at 4°C, all of 15 selected strains (5 strains each of Salmonella spp., STEC O157, and STEC O26) died after 35 to 70 days of storage at 25°C and 35°C. The survival rates of all of these 15 strains in paper disks after the 24 h of drying were substantially increased (10 to 79 times) by the presence of sucrose (12% to 36%). All of these 15 desiccated strains in paper disks survived after exposure to 70°C for 5 h. The populations of these 15 strains inoculated in dried foods containing sucrose and/or fat (e.g., chocolate) were 100 times higher than those in the dried paper disks after drying for 24 h at 25°C.
Fast and high-quality regional histogram equalization

In this paper, we propose a novel adaptive histogram equalization method. In our proposed method, an image is divided into several blocks and histogram equalization (HE) is performed for each block. We utilize dynamic range separate histogram equalization (DRSHE) for each block and realize quasi-regional histogram equalization. Experimental results indicate that the performance of our proposed method is very similar to that of the Retinex method, whereas the computation time is much smaller than that of the Retinex method.
Leishmania vaccines: from leishmanization to the era of DNA technology

Leishmania are obligate intracellular vector-borne parasites that cause significant morbidity and mortality in many countries worldwide. There are several species of the parasite which vary according to geographical location and cause a variety of clinical syndromes ranging from self-limiting cutaneous lesions to potentially fatal infection of the viscera. The disease manifested is dependent on both the species of the parasite and the immune response of the host. Depending on the species of the parasite, resistance to infection is generally associated with a T-helper-1 immune response that activates macrophages to kill intracellular Leishmania in a nitric oxide-dependent manner. Conversely, disease progression is generally associated with a T-helper-2 response that activates humoral immunity. Chemotherapeutic treatments for leishmaniasis exist but are expensive, toxic and ineffective against resistant strains. A vaccine against leishmaniasis is feasible since most individuals that were once infected become resistant to clinical infection when later exposed. However, despite the wealth of information regarding the genetics of the parasite and the experimental immunology of the disease, there is currently no vaccine against Leishmania. A multitude of vaccine strategies have been pursued including the use of killed and genetically modified parasites. Immunization with naked plasmid DNA encoding Leishmania antigens represents a new approach to a Leishmania vaccine and confers several advantages over the more traditional vaccination methods. In order to develop an effective vaccine against leishmaniasis, it is important to understand the mechanisms of the immune response to Leishmania infection. This review discusses such immune mechanisms in detail and also explores several of the Leishmania vaccination strategies employed to date, with particular emphasis on DNA vaccines.
Functional characterisation of a natural androgen receptor missense mutation (N771H) causing human androgen insensitivity syndrome

Androgen insensitivity syndrome (AIS) is an X‐linked disorder due to mutations of androgen receptor (AR) gene. Various AR mutations have been identified, and the characterisation of these mutations greatly facilitates our understanding of AR structure–function. In this study, we have analysed an AR missense mutation (N771H) identified in patients with AIS. Functional analysis of the mutant AR was performed by in vitro mutagenesis–cotransfection assays. Compared to the wild‐type AR, the dose–response curve of dihydrotestosterone‐induced transactivation activity in the mutant AR was greatly shifted to the right and significantly decreased. However, the maximal efficacy of transactivation activity in the mutant AR was similar to that of the wild type. Receptor binding assay indicated that the mutant AR had an approximately 2.5‐fold lower binding affinity to dihydrotestosterone compared to the wild type. Western blot analysis showed that the size and the expression level of mutant AR in transfected cells were comparable to the wild type. These data underscore the importance of asparagine at amino acid position 771 of human AR in normal ligand binding and normal receptor function, and a mutation at this position results in androgen insensitivity in affected subjects.
Recommendations on use of biomarkers in alcoholism treatment trials.

BACKGROUND Biochemical markers of heavy drinking are playing increasingly prominent roles in alcohol treatment efficacy studies, especially in those designed to evaluate medications. Among these roles are serving as inclusion or exclusion criteria for research participants, corroboration of self-report of drinking status, assessment of the safety of the agent being evaluated, and determination of treatment outcome. METHODS Recent alcohol medication development trials that included biomarker information were reviewed and critiqued from the perspectives of how biomarker measures were used and how findings on them were reported. RESULTS Although generally the application of biomarkers as inclusion criteria is not recommended, they may aid in exclusion of potential subjects (e.g., elevated liver function measures in trials of agents that could result in liver damage). Biomarkers are most commonly used as indicators of outcome, usually serving as secondary outcome variables. The relationship of outcome findings on biomarker and self-report measures is positive, but only moderate. As used to date, biomarkers of drinking tend to be less sensitive than well-standardized and properly administered self-report measures. Nevertheless, they do provide a useful, unique source of information on drinking status. CONCLUSIONS The contribution of biomarkers to alcoholism clinical research would be enhanced if certain design strategies were incorporated into their application and if critical information were included in the research publication. This article offers a series of recommendations to improve on their use in a research context.
Prevention of Sports Injuries by Marine Omega-3 Fatty Acids

Sport injuries are common and costly for the professional athlete, the “weekend warrior,” and the community. Acute injuries are treated according to current guidelines with the aim of bringing the athlete back into the arena. These guidelines have not taken into account new scientific results of the inflammatory process following a trauma. The 4 hallmarks of inflammation, namely, pain, swelling, redness, and heat, are results of an adequate inflammatory response with the aim of bringing the affected tissue back to restitution (Latin: restitutio ad integrum). Cooling of the affected limb and anti-inflammatory drugs are widely used but may deter healing. The healing process is governed by fatty acids of the omega-3 and omega-6 series. In order to facilitate healing, these fatty acids have to be present in significant amounts in the affected tissues before the trauma occurs. This is particularly relevant for marine omega-3 fatty acids, which are often running low due to insignificant intake of seafood, common in individuals practicing sports. High-energy sports often lead to head and brain trauma. Continuous head traumata may even result in later mental defects. Saturation of brain cells with omega-3 fatty acids, in particular docosahexaenoic acid (DHA), may facilitate healing after brain trauma, thereby counteracting negative long-term results. The present understanding of a normal inflammatory process leading to restitution will be discussed along with data from recent scientific trials.