Miracle-dz/UniFAR-FTUs huggingface dataset:
MED28 and forkhead box M1 (FOXM1) mediate matrix metalloproteinase 2 (MMP2)‐dependent cellular migration in human nonsmall cell lung cancer (NSCLC) cells

Non‐small‐cell lung cancer (NSCLC) accounts for the majority of the lung cancer cases that have become a leading cause of cancer deaths worldwide. Overexpression of transcription factor forkhead box M1 (FOXM1) is involved in the inauspicious development of several types of cancer, including lung tumor aggressiveness. Our laboratory has previously found that MED28, a Mediator subunit for transcriptional activation, modulates cell growth, epithelial‐mesenchymal transition, migration, and invasion in human breast cancer cells. The objective of the current study is to investigate the potential role of MED28 and FOXM1 in NSCLC. In addition to A549 and PC9 cells, we also used a doxycycline‐inducible system to generate FOXM1‐overexpressed A549‐DN cells, and we explored the connection of MED28 with FOXM1 and their effect on migration. Herein, we report that the increased expression levels of both MED28 and FOXM1 elevated the expression of matrix metalloproteinase 2 (MMP2), a metastasis marker, which enhanced cell migration and matrigel invasion of NSCLC cells. Furthermore, MED28 interacted with FOXM1, and both exhibited a mutual effect on the expression and subcellular localization. Moreover, MED28 small interfering RNA‐mediated MMP2 gene suppression could be attenuated by inducible expression of a constitutively active form of FOXM1, which consequently restored the migration and invasion ability of NSCLC cells. Our data indicate that MED28 interacts with FOXM1, and each affects the expression and localization of the other, and, more importantly, both regulate MMP2‐dependent migration and invasion in human lung cancer cells.
Steerable catheters for minimally invasive surgery: a review and future directions

Abstract The steerable catheter refers to the catheter that is manipulated by a mechanism which may be driven by operators or by actuators. The steerable catheter for minimally invasive surgery has rapidly become a rich and diverse area of research. Many important achievements in design, application and analysis of the steerable catheter have been made in the past decade. This paper aims to provide an overview of the state of arts of steerable catheters. Steerable catheters are classified into four main groups based on the actuation principle: (1) tendon driven catheters, (2) magnetic navigation catheters, (3) soft material driven catheters (shape memory effect catheters, steerable needles, concentric tubes, conducting polymer driven catheters and hydraulic pressure driven catheters), and (4) hybrid actuation catheters. The advantages and limitations of each of them are commented and discussed in this paper. The future directions of research are summarized.
Identification and characterization of GLDC as host susceptibility gene to severe influenza

Glycine decarboxylase (GLDC) was prioritized as a candidate susceptibility gene to severe influenza in humans. The higher expression of GLDC derived from genetic variations may confer a higher risk to H7N9 and severe H1N1 infection. We sought to characterize GLDC as functional susceptibility gene that GLDC may intrinsically regulate antiviral response, thereby impacting viral replication and disease outcome. We demonstrated that GLDC inhibitor AOAA and siRNA depletion boosted IFNβ‐ and IFN‐stimulated genes (ISGs) in combination with PolyI:C stimulation. GLDC inhibition and depletion significantly amplified antiviral response of type I IFNs and ISGs upon viral infection and suppressed the replication of H1N1 and H7N9 viruses. Consistently, GLDC overexpression significantly promoted viral replication due to the attenuated antiviral responses. Moreover, GLDC inhibition in H1N1‐infected BALB/c mice recapitulated the amplified antiviral response and suppressed viral growth. AOAA provided potent protection to the infected mice from lethal infection, comparable to a standard antiviral against influenza viruses. Collectively, GLDC regulates cellular antiviral response and orchestrates viral growth. GLDC is a functional susceptibility gene to severe influenza in humans.
Dietary Protein and Carbohydrates Affect Immune Function and Performance in a Specialist Herbivore Insect (Manduca sexta)

Nutrition structures ecology and evolution across all scales of biological organization. It is well known that nutrition can have direct effects on performance and fitness, but indirect effects on physiological systems that mediate biotic interactions have been studied less frequently. Here, we focus on the interaction between nutrition, performance, and the immune system in a specialist herbivorous insect, Manduca sexta. We used a conceptual framework in nutritional ecology (the geometric framework) to examine how changes in diet quality affect aspects of the immune system used for defense against parasitoids. We raised caterpillars throughout their entire larval development on five different experimental diets that varied in protein and carbohydrate content and measured five aspects of the immune system: encapsulation, phenoloxidase activity, prophenoloxidase activity, total hemolymph protein, and hemocyte density. Overall, different parts of the immune function varied in response to interactions between carbohydrates, protein, and intake, but protein reductions had the largest impacts—mostly detrimental. In addition, our data suggest that diet quality mediates the relationship between performance (growth and survival) and immune function, as well as trade-offs among different components of immune function. Our work is the first to examine the interplay between nutrition, performance, and immune function with the geometric framework in a specialist insect herbivore.
Role of cyclic and pseudo-cyclic electron transport in response to dynamic light changes in Physcomitrella patens.

Photosynthetic organisms support cell metabolism by harvesting sunlight and driving the electron transport chain at the level of thylakoid membranes. Excitation energy and electron flow in the photosynthetic apparatus is continuously modulated in response to dynamic environmental conditions. Alternative electron flow around photosystem I plays a seminal role in this regulation contributing to photoprotection by mitigating overreduction of the electron carriers. Different pathways of alternative electron flow coexist in the moss Physcomitrella patens, including cyclic electron flow mediated by the PGRL1/PGR5 complex and pseudo-cyclic electron flow mediated by the flavodiiron proteins FLV. In this work, we generated P. patens plants carrying both pgrl1 and flva knock-out mutations. A comparative analysis of the WT, pgrl1, flva, and pgrl1 flva lines suggests that cyclic and pseudo-cyclic processes have a synergic role in the regulation of photosynthetic electron transport. However, although both contribute to photosystem I protection from overreduction by modulating electron flow following changes in environmental conditions, FLV activity is particularly relevant in the first seconds after a light change whereas PGRL1 has a major role upon sustained strong illumination.
Peri/epicellular protein disulfide isomerase-A1 acts as an upstream organizer of cytoskeletal mechanoadaptation in vascular smooth muscle cells.

Although redox processes closely interplay with mechanoresponses to control vascular remodeling, redox pathways coupling mechanostimulation to cellular cytoskeletal organization remain unclear. The peri/epicellular pool of protein disulfide isomerase-A1 (pecPDIA1) supports postinjury vessel remodeling. Using distinct models, we investigated whether pecPDIA1 could work as a redox-dependent organizer of cytoskeletal mechanoresponses. In vascular smooth muscle cells (VSMCs), pecPDIA1 immunoneutralization impaired stress fiber assembly in response to equibiaxial stretch and, under uniaxial stretch, significantly perturbed cell repositioning perpendicularly to stretch orientation. During cyclic stretch, pecPDIA1 supported thiol oxidation of the known mechanosensor β1-integrin and promoted polarized compartmentalization of sulfenylated proteins. Using traction force microscopy, we showed that pecPDIA1 organizes intracellular force distribution. The net contractile moment ratio of platelet-derived growth factor-exposed to basal VSMCs decreased from 0.90 ± 0.09 (IgG-exposed controls) to 0.70 ± 0.08 after pecPDI neutralization ( P < 0.05), together with an enhanced coefficient of variation for distribution of force modules, suggesting increased noise. Moreover, in a single cell model, pecPDIA1 neutralization impaired migration persistence without affecting total distance or velocity, whereas siRNA-mediated total PDIA1 silencing disabled all such variables of VSMC migration. Neither expression nor total activity of the master mechanotransmitter/regulator RhoA was affected by pecPDIA1 neutralization. However, cyclic stretch-induced focal distribution of membrane-bound RhoA was disrupted by pecPDI inhibition, which promoted a nonpolarized pattern of RhoA/caveolin-3 cluster colocalization. Accordingly, FRET biosensors showed that pecPDIA1 supports localized RhoA activity at cell protrusions versus perinuclear regions. Thus, pecPDI acts as a thiol redox-dependent organizer and noise reducer mechanism of cytoskeletal repositioning, oxidant generation, and localized RhoA activation during a variety of VSMC mechanoresponses. NEW & NOTEWORTHY Effects of a peri/epicellular pool of protein disulfide isomerase-A1 (pecPDIA1) during mechanoregulation in vascular smooth muscle cells (VSMCs) were highlighted using approaches such as equibiaxial and uniaxial stretch, random single cell migration, and traction force microscopy. pecPDIA1 regulates organization of the cytoskeleton and minimizes the noise of cell alignment, migration directionality, and persistence. pecPDIA1 mechanisms involve redox control of β1-integrin and localized RhoA activation. pecPDIA1 acts as a novel organizer of mechanoadaptation responses in VSMCs.
Introduction to the Special Issue on AI for Long-Term Autonomy

The papers in this special section focus on the use of artificial intelligence (AI) for long term autonomy. Autonomous systems have a long history in the fields of AI and robotics. However, only through recent advances in technology has it been possible to create autonomous systems capable of operating in long-term, real-world scenarios. Examples include autonomous robots that operate outdoors on land, in air, water, and space; and indoors in offices, care homes, and factories. Designing, developing, and maintaining intelligent autonomous systems that operate in real-world environments over long periods of time, i.e. weeks, months, or years, poses many challenges. This special issue focuses on such challenges and on ways to overcome them using methods from AI. Long-term autonomy can be viewed as both a challenge and an opportunity. The challenge of long-term autonomy requires system designers to ensure that an autonomous system can continue operating successfully according to its real-world application demands in unstructured and semi-structured environments. This means addressing issues related to hardware and software robustness (e.g., gluing in screws and profiling for memory leaks), as well as ensuring that all modules and functions of the system can deal with the variation in the environment and tasks that is expected to occur over its operating time.
Multiple components of the nuclear pore complex interact with the amino-terminus of MX2 to facilitate HIV-1 restriction

Human myxovirus resistance 2 (MX2/MXB) is an interferon-induced post-entry inhibitor of human immunodeficiency virus type-1 (HIV-1) infection. While the precise mechanism of viral inhibition remains unclear, MX2 is localized to the nuclear envelope, and blocks the nuclear import of viral cDNAs. The amino-terminus of MX2 (N-MX2) is essential for anti-viral function, and mutation of a triple arginine motif at residues 11 to 13 abrogates anti-HIV-1 activity. In this study, we sought to investigate the role of N-MX2 in anti-viral activity by identifying functionally relevant host-encoded interaction partners through yeast-two-hybrid screening. Remarkably, five out of seven primary candidate interactors were nucleoporins or nucleoporin-like proteins, though none of these candidates were identified when screening with a mutant RRR11-13A N-MX2 fragment. Interactions were confirmed by co-immunoprecipitation, and RNA silencing experiments in cell lines and primary CD4+ T cells demonstrated that multiple components of the nuclear pore complex and nuclear import machinery can impact MX2 anti-viral activity. In particular, the phenylalanine-glycine (FG) repeat containing cytoplasmic filament nucleoporin NUP214, and transport receptor transportin-1 (TNPO1) were consistently required for full MX2, and interferon-mediated, anti-viral function. Both proteins were shown to interact with the triple arginine motif, and confocal fluorescence microscopy revealed that their simultaneous depletion resulted in diminished MX2 accumulation at the nuclear envelope. We therefore propose a model whereby multiple components of the nuclear import machinery and nuclear pore complex help position MX2 at the nuclear envelope to promote MX2-mediated restriction of HIV-1.
Effect of Remediating Blighted Vacant Land on Shootings: A Citywide Cluster Randomized Trial.

OBJECTIVES To determine if remediating blighted vacant urban land reduced firearm shooting incidents resulting in injury or death. METHODS We conducted a cluster randomized controlled trial in which we assigned 541 randomly selected vacant lots in Philadelphia, Pennsylvania, to 110 geographically contiguous clusters and randomly assigned these clusters to a greening intervention, a less-intensive mowing and trash cleanup intervention, or a no-intervention control condition. The random assignment to the trial occurred in April and June 2013 and lasted until March 2015. In a difference-in-differences analysis, we assessed whether the 2 treatment conditions relative to the control condition reduced firearm shootings around vacant lots. RESULTS During the trial, both the greening intervention, -6.8% (95% confidence interval [CI] = -10.6%, -2.7%), and the mowing and trash cleanup intervention, -9.2% (95% CI = -13.2%, -4.8%), significantly reduced shootings. There was no evidence that the interventions displaced shootings into adjacent areas. CONCLUSIONS Remediating vacant land with inexpensive, scalable methods, including greening or minimal mowing and trash cleanup, significantly reduced shootings that result in serious injury or death. Public Health Implications. Cities should experiment with place-based interventions to develop effective firearm violence-reduction strategies. TRIAL REGISTRATION This trial was registered with the International Standard Randomized Controlled Trial Number (study ID ISRCTN92582209; http://www.isrctn.com/ISRCTN92582209 ). (Am J Public Health. Published online ahead of print November 29, 2018: e1-e5. doi:10.2105/AJPH.2018.304752).
Chemokine-Regulated Recruitment of Antigen-Specific T-Cell Subpopulations to the Liver in Acute and Chronic Hepatitis C Infection.

BACKGROUND In hepatitis C virus (HCV) infection, virus-specific CD8+ T cells are recruited to the liver for antiviral activity. Multiple chemokine ligands are induced by the infection, notably interferon-inducible chemokine, CXCL10. In HCV, intrahepatic T cells express chemokine receptors (CCRs), including CXCR3, CXCR6, CCR1, and CCR5, but CCR expression on antigen-specific effector and memory T cells has not been investigated. METHODS Paired blood and liver samples were collected from subjects with chronic HCV for flow cytometric analysis of CCR expression on CD8+ T cells. Expression of these CCRs was then examined on HCV-specific CD8+ T-cell subpopulations in the blood from subjects with acute or chronic HCV. RESULTS Relative to peripheral blood, the liver was enriched with CD8+ T cells expressing CCR2, CCR5, CXCR3, and CXCR6 either singly or in combinations. CXCR3 was preferentially expressed on HCV-specific CD8+ T cells in both acute and chronic phases of infection in blood. Both CXCR3 and CCR2 were overexpressed on HCV-specific CD8+CCR7+CD45RO+ (central memory) cells, whereas effector memory (CD8+CCR7-CD45RO+) cells expressed more CXCR6. CONCLUSIONS CXCR3-mediated signals support the accumulation of HCV-specific CD8+ memory T cells in the infected liver, and emphasize the importance of the CXCL10/CXCR3 trafficking pathway during acute and chronic HCV infection.
Expression of Vascular Endothelial Growth Factor and Microvessel Density in Psoriatic Skin Lesions

Background: Psoriasis is a common chronic and immune-mediated skin disorder having a significant impact on the patient's quality of life. An analysis of the role of angiogenic vascular endothelial growth factor (VEGF) expression and microvessel density in psoriatic skin lesions may help in better understanding of the disease pathogenesis. The aim of this study was to examine the expression of vascular endothelial growth factor (VEGF) and microvessel density using CD34 antibodies in psoriatic skin lesions by immunohistochemical examination using normal skin of healthy individuals as controls. Materials and Methods: Patients with clinical diagnosis of plaque type of psoriasis (e.g., chronic plaque) (n = 49) were included in the study. 5-mm punch biopsies were taken from the psoriatic skin lesions in these patients. A total of 20 punch biopsies were taken from the control group comprising of 20 healthy volunteers. The biopsies were subjected to histopathological examination for confirmation of diagnosis and grading. Immunohistochemical evaluation was done for the expression of VEGF, and microvessel density was assessed using CD34 and compared with the controls. Results: An increased VEGF expression by keratinocytes (49.80% ± 21.16%) and microvessel density in the papillary dermis (15.302% ± 3.8061%) was observed in patients with psoriasis, which was significantly higher as compared to controls (P < 0.0001). A significant positive correlation was observed between VEGF expression by keratinocytes and the microvessel density in the dermis (r = 0.664, P = 0.01). No significant correlation was observedbetween the histopathological grade of psoriasis and microvessel density, or with the VEGF expression. Conclusion: VEGF expression ascertained to be a significant factor in the pathogenesis of psoriasis.
Effects of Wolbachia/Cardinium Infection on the Mitochondrial Phylogeny of Oligonychus castaneae (Acari: Tetranychidae)

Abstract A wide range of invertebrates harbor intracellular endosymbiotic bacteria. Within these endosymbionts, Wolbachia and Cardinium, have been attracting particular attention because these bacteria frequently affect the genetic structure and genetic diversity of their hosts. They cause various reproductive alterations such as cytoplasmic incompatibility, parthenogenesis induction, male-killing, and feminization. Through these alterations, they also affect the maternally inherited organelles of their hosts. Mitochondrial DNA (mtDNA) can be used for molecular phylogenetic analysis of invertebrates. However, in Wolbachia- or Cardinium-infected invertebrates, phylogenetic trees based on mtDNA are often inconsistent with those based on nuclear DNA. In the present study, we determined the Wolbachia/Cardinium infection status of 45 populations of the mite, Oligonychus castaneae Ehara & Gotoh (Acari: Tetranychidae), collected throughout Japan. Then, we compared phylogenetic trees of O. castaneae based on both the cytochrome c oxidase subunit I (COI) gene of mtDNA and the 28S rRNA gene of nuclear DNA to clarify the effects of Wolbachia and/or Cardinium infection. We found 106 Wolbachia-infected individuals and 250 Cardiniuminfected individuals in a total of 450 individuals, indicating an infection rate of 79%. No double-infected individuals were observed. In the 28S tree, almost all populations formed a single group. In the COI tree, O. castaneae formed four separate groups that more closely followed Wolbachia/Cardinium infection than geographic distribution. These results strongly suggest that the endosymbionts affected mitochondrial variation of O. castaneae.
Clinical Reasoning in Physical Therapy: A Concept Analysis

BACKGROUND Physical therapy, along with most health professions, struggles to describe clinical reasoning, despite it being a vital skill in effective patient care. This lack of a unified conceptualization of clinical reasoning leads to variable and inconsistent teaching, assessment, and research. OBJECTIVE The objective was to conceptualize a broad description of physical therapists' clinical reasoning grounded in the published literature and to unify understanding for future work related to teaching, assessment, and research. DESIGN/METHODS The design included a systematic concept analysis using Rodgers' evolutionary methodology. A concept analysis is a research methodology in which a concept's characteristics and the relation between features of the concept are clarified. RESULTS Based on findings in the literature, clinical reasoning in physical therapy was conceptualized as integrating cognitive, psychomotor, and affective skills. It is contextual in nature and involves both therapist and client perspectives. It is adaptive, iterative, and collaborative with the intended outcome being a biopsychosocial approach to patient/client management. LIMITATIONS Although a comprehensive approach was intended, it is possible that the search methods or reduction of the literature were incomplete or key sources were mistakenly excluded. CONCLUSIONS A description of clinical reasoning in physical therapy was conceptualized, as it currently exists in representative literature. The intent is for it to contribute to the unification of an understanding of how clinical reasoning has been conceptualized to date by practitioners, academicians, and clinical educators. Substantial work remains to further develop the concept of clinical reasoning for physical therapy, including the role of movement in our reasoning in practice.
An investigation into the effective factors on the acceptance and use of integrated health system in the primary health-care centers

BACKGROUND: The successful application of the information systems in the health-care domain requires a reasonable recognition of the factors affecting the acceptance and use of such systems. The study aimed to investigate the factors affecting the acceptance and use of an integrated health system (IHS) in Isfahan primary health centers. MATERIALS AND METHODS: It was an applied and descriptive–analytical survey conducted in Isfahan, Iran. Research population included all IHS's users in the health centers no. 1 and 2 of Isfahan city from which a sample of 320 individuals were selected in total. Data were collected using a questionnaire developed based on the Unified Theory of Acceptance and Use of Technology model. Data were analyzed using partial least squares (PLS) method and SmartPLS software. RESULTS: The users’ behavioral intention to use the IHS system was influenced by performance expectancy, effort expectancy, and social influence, but it was not significantly related to facilitating conditions. Behavioral intention to use the IHS also had a significant relationship with the use of system. Furthermore, performance expectancy was the most important predictor. CONCLUSIONS: According to the findings, if the system users perceive the positive role of system in performance improvement, its convenience to use, and positive attitude of others toward it, their willingness to accept and use system will increase. Furthermore, it was important for the users that the system helps them in resolving their daily work-related problems and making rational decisions.