Miracle-dz/UniFAR-FTUs huggingface dataset:
Pseudomonas aeruginosa‐derived rhamnolipids subvert the host innate immune response through manipulation of the human beta‐defensin‐2 expression

Pseudomonas aeruginosa is a well‐known cause of infections especially in compromised patients. To neutralize this pathogen, the expression of antimicrobial factors in epithelial cells is crucial. In particular the human beta‐defensin hBD‐2 is especially active against P. aeruginosa. In this study, we identified rhamnolipids in P. aeruginosa culture supernatants that are able to prevent the pathogen‐induced hBD‐2 response in keratinocytes. The presence of rhamnolipids within the host cells and inhibition assays suggest that calcium‐regulated pathways and protein kinase C activation are impaired by rhamnolipids. In consequence, the induction of hBD‐2 in keratinocytes by P. aeruginosa‐derived flagellin as well as the host's own hBD‐2 mediator interleukin IL‐1β is inhibited. Strikingly, rhamnolipids did not affect the release of the proinflammatory mediator interleukin IL‐8 by flagellin. Thus, in addition to their function in establishment and persistence of P. aeruginosa infections, rhamnolipids can be engaged by P. aeruginosa for a targeted attenuation of the innate immunity to manage its survival and colonization on compromised epithelia.
Hypoxia causes glycogenolysis without an increase in percent phosphorylase a in rat skeletal muscle.

Stimulation of skeletal muscle to contract activates phosphorylase b-to-a conversion and glycogenolysis. Despite reversal of the increase in percentage of phosphorylase a after a few minutes, continued glycogen breakdown can occur during strenuous exercise. Hypoxia causes sustained glycogenolysis in skeletal muscle without an increase in percentage of phosphorylase a. We used this model to obtain insights regarding how glycogenolysis is mediated in the absence of an increase in percentage of phosphorylase a. Hypoxia caused a 70% decrease in glycogen in epitrochlearis muscles during an 80-min incubation despite no increase in percentage of phosphorylase a above the basal level of approximately 10%. Muscle Pi concentration increased from 3.8 to 8.6 mumol/g muscle after 5 min and 15.7 mumol/g after 20 min. AMP concentration doubled, attaining a steady state of 0.23 mumol/g in 5 min. Incubation of oxygenated muscles with 0.1 microM epinephrine induced an approximately sixfold increase in percentage of phosphorylase a but resulted in minimal glycogenolysis. Muscle Pi concentration was not altered by epinephrine. Despite no increase in percentage of phosphorylase a, hypoxia resulted in a fivefold greater depletion of glycogen over 20 min than did epinephrine. To evaluate the role of phosphorylase b, muscles were loaded with 2-deoxyglucose 6-phosphate, which inhibits phosphorylase b. The rate of glycogenolysis during 60 min of hypoxia was reduced by only approximately 14% in 2-deoxyglucose 6-phosphate-loaded muscles. (ABSTRACT TRUNCATED AT 250 WORDS)
Enhanced tight junction function in human breast cancer cells by antioxidant, selenium and polyunsaturated lipid

Paracellular permeability (PCP) is governed by tight junctions (TJs) in epithelial cells, acting as cell–cell adhesion structures, the aberration of which is known to be linked to the dissociation and metastasis of breast cancer cells. This study hypothesized that the function of TJs in human breast cancer cells can be augmented by gamma linolenic acid (GLA), selenium (Se), and iodine (I) in the presence of 17‐β‐estradiol, as these molecules are known to increase TJ functions in endothelial cells, using assays of trans‐epithelial resistance (TER), PCP, immunofluorescence, and in vitro invasion and motility models. GLA, I, and Se individually increased TER of MDA‐MB‐231 and MCF‐7 human breast cancer cells. The combination of all three agents also had a significant increase in TER. Addition of GLA/Se/I reduced PCP of both breast cancer cell lines. GLA/Se/I reversed the effect of 17‐β‐estradiol (reduced TER, increased PCP). Immunofluorescence revealed that after treatment with Se/I/GLA over 24 h, there was increasing relocation to breast cancer cell–cell junctions of occludin and ZO‐1 in MCF‐7 cells. Moreover, treatment with GLA/Se/I, alone or in combination, significantly reduced in vitro invasion of MDA‐MB‐231 cells through an endothelial cell barrier (P < 0.0001) and reduced 17‐β‐estradiol induced breast cancer cell motility (P < 0.0001). Our previous work has demonstrated that GLA, I, and Se alone, or in combination are able to strengthen the function of TJs in human endothelial cells; this has now proved to be true of human breast cancer cells. This combination also completely reversed the effect of 17‐β‐estradiol in these cells. J. Cell. Biochem. 101: 155–166, 2007. © 2007 Wiley‐Liss, Inc.
Redox Nanoparticle Therapeutics for Acetaminophen-Induced Hepatotoxicity in Mice

The purpose of this study was to evaluate the hepatoprotective effect of an antioxidative nanoparticle (RNPN) recently developed against APAP-induced hepatotoxicity in mice. The effects of oral administration of RNPN to APAP-treated mice were assessed for various biochemical liver function parameters: alanine transaminase (ALT) activity, aspartate transaminase (AST) activity, alkaline phosphatase (ALP) activity, prothrombin time, and serum albumin (ALB) level. The treatment effects were assessed in terms of free radical parameters: malondialdehyde (MDA) accumulation, glutathione peroxidase (GPx) activity, % inhibition of superoxide anion (O2 −∙), and histopathological examination. The N-acetylcysteine (NAC)-treated group exhibited an enhanced prothrombin time relative to the control group, while RNPN did not prolong prothrombin time. The RNPN-treated animals exhibited lower levels of ALT, AST, and ALP, while increased ALB levels were measured in these animals compared to those in the other groups. The RNPN-treated animals furthermore exhibited improved MDA levels, GPx activity, and % inhibition of O2 −∙, which relate to oxidative damage. Histological staining of liver tissues from RNPN-treated animals did not reveal any microscopic changes relative to the other groups. The findings of this study suggest that RNPN possesses effective hepatoprotective properties and does not exhibit the notable adverse effects associated with NAC treatment.
Phospholipase Cϵ Suppresses Integrin Activation*

Phospholipase Cϵ (PLCϵ) is a newly described effector of the small GTP-binding protein H-Ras. Utilizing H-Ras effector mutants, we show that mutants H-Ras(G12V/E37G) and H-Ras(G12V/D38N) suppressed integrin activation in an ERK-independent manner. H-Ras(G12V/D38N) specifically activated the PLCϵ effector pathway and suppressed integrin activation. Inhibition of PLCϵ activation with a kinase-dead PLCϵ mutant prevented H-Ras(G12V/D38N) from suppressing integrin activation, and low level expression of H-Ras(G12V/D38N) could synergize with wild-type PLCϵ to suppress integrins. In addition, knockdown of endogenous PLCϵ with small interfering RNA blocked H-Ras(G12V/D38N)-mediated integrin suppression. Suppressing integrin function with the H-Ras(G12V/D38N) mutant reduced cell adhesion to von Willebrand factor and fibronectin; this reduction in cell adhesion was blocked by coexpression of the kinase-dead PLCϵ mutant. These results show that H-Ras suppresses integrin affinity via independent Raf and PLCϵ signaling pathways and demonstrate a new physiological function for PLCϵ in the regulation of integrin activation.
Racial differences in clinical and pathological associations with PhIP‐DNA adducts in prostate

African–American men have a higher dietary intake of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP), which is the most abundant heterocyclic amine in cooked meats and is carcinogenic in rat prostate through the formation of DNA adducts. To determine the clinical and demographic factors associated with PhIP‐DNA adduct levels, the biologically effective dose of PhIP in human prostate, we immunohistochemically measured PhIP‐DNA adducts in a study of 162 Caucasian and 102 African–American men who underwent radical prostatectomy for prostate cancer. A strong correlation between PhIP‐DNA adduct levels in prostate tumor and adjacent non‐tumor cells was observed (ρ = 0.62; p < 0.0001); however, non‐tumor cells had significantly higher adduct levels compared with tumor (0.167 optical density (OD) units ± 0.043 vs. 0.104 OD ± 0.027; p < 0.0001). Race was not associated with PhIP‐DNA adduct levels in either tumor or non‐tumor cells, but race‐specific associations were observed. In prostate tumor and non‐tumor cells, tumor volume had the strongest association with PhIP‐DNA adducts in Caucasians, whereas in African–Americans prostate volume was most strongly associated with adduct levels in tumor cells and advanced Gleason grade had the strongest association in non‐tumor cells. In race interaction models, while the only statistically significant interaction was between African–American race and advanced Gleason grade in non‐tumor cells (β = 0.029; p = 0.02), in tumor cells we observed opposite effects by race (positive for African–Americans, negative for Caucasians) for older age and high PSA levels at diagnosis. In conclusion, while PhIP‐DNA adduct levels in prostate cells do not vary significantly by race, our results suggest that PhIP exposure may have stronger effects on prostate tumor differentiation in African–American men. © 2007 Wiley‐Liss, Inc.
A6 Peptide Activates CD44 Adhesive Activity, Induces FAK and MEK Phosphorylation, and Inhibits the Migration and Metastasis of CD44-Expressing Cells

The A6 peptide (acetyl-KPSSPPEE-amino) has antitumor activity in the absence of significant adverse events in murine tumor models and clinical trials. A6 shares sequence homology with CD44, an adhesion receptor involved in metastasis that is also a marker of cancer stem cells and drug-resistant phenotypes. We investigated the mechanism of action of A6 by examining its effects on CD44 activity, cell migration, and metastasis. A6 inhibited the migration of a subset of ovarian and breast cancer cell lines, exhibiting IC50 values of 5 to 110 nmol/L. The ability of A6 to inhibit migration in vitro correlated with CD44 expression. Immunopreciptation studies showed that CD44 binds A6 and that biotin-tagged A6 can be cross-linked to CD44. The binding of A6 altered the structure of CD44 such that it was no longer recognized by a monoclonal antibody to a specific epitope. Importantly, A6 potentiated the CD44-dependent adhesion of cancer cells to hyaluronic acid and activated CD44-mediated signaling, as evidenced by focal adhesion kinase and MAP/ERK kinase phosphorylation. In vivo, A6 (100 mg/kg delivered s.c. twice daily) reduced the number of lung foci generated by the i.v. injection of B16-F10 melanoma cells by 50% (P = 0.029 in an unpaired t test). We conclude that A6 potently blocks the migration of CD44-positive cells in vitro through an interaction with CD44 that alters its structure and activates CD44 to enhance ligand binding and downstream signaling. The concurrent ability of A6 to agonize the CD44 receptor suggests that CD44 activation may represent a novel strategy for inhibiting metastatic disease. Mol Cancer Ther; 10(11); 2072–82. ©2011 AACR.
Proportional changes in cephalometric distances during Twin Block appliance therapy.

The aim of the study was to evaluate the cephalometric changes produced by the Twin Block appliance. Lateral cephalometric radiographs were taken before and after Twin Block appliance treatment on 30 consecutive patients (14 male, 16 female, mean age 12 years 6 months). Published normative data tables were used to produce control data, which were individually matched to the test group for age, sex, and treatment time. Alteration in shape was assessed by measuring percentage change in linear dimensions as opposed to change in cephalometric angles used in previous investigations. The differential average percentage change was calculated by subtracting the control value from the Twin Block value. Clinically significant changes (2 per cent and greater) were found in lower anterior (6.6 per cent) and posterior (4.6 per cent) face heights, upper incisor to maxillary plane (4.9 per cent), i.e. upper incisor retraction, and increase in mandibular length (Co-B 3.3 per cent, Co-Po 2.6 per cent, Ar-B 3.5 per cent, Ar-Po 2.2 per cent).
Unit Manager's Role with Family Members of Clients in Complex Continuing Care Settings: An Untold Story*

ABSTRACT Most literature on staff-family relationships has come from studies of long-term care settings, has focused mainly on the families' perspectives on factors affecting their relationships with staff, and has included scant findings from the staff's perspective. No studies that examined staff-family relationships in complex continuing care (CCC) environments from the perspective of staff were found in the literature. A qualitative study that draws on a grounded theory approach was conducted to explore staff-family relationships in CCC, and the findings presented in this article illuminate the unit manager's role. Data were collected through in-depth interviews with nine unit managers and a follow-up focus group with five unit managers who work in three CCC facilities. Three categories reflecting the unit manager's role with family members of clients in CCC settings were derived: establishing supportive entry; building and preserving relationships; and closing the loop. Implications of the findings for practice and future research are presented. RÉSUMÉ Á ce jour, la plupart des écrits scientifiques portant sur les relations entre le personnel et les familles découlent d'études portant sur des soins de longue durée. Ils mettent essentiellement l'accent sur la perspective des familles à l'égard des facteurs qui influencent leur relation avec le personnel, et comportent peu de conclusions liées à la perspective du personnel. Nous n'avons trouvé, dans la documentation spécialisée, aucune étude portant sur les relations entre le personnel et la famille, dans des établissements de soins complexes de longue durée, où l'on partait de la perspective du personnel. Une étude qualitative fondée sur l'approche de la théorie ancrée a été menée afin d'étudier les relations entre le personnel et les familles dans un établissement de soins complexes de longue durée. Les résultats présentés dans cet article permettent de mettre en lumière le rôle du gestionnaire d'unité. Les données ont été recueillies au moyen d'entrevues approfondies menées auprès de neuf gestionnaires d'unité et d'un groupe de discussion composé de cinq gestionnaires d'unité travaillant dans trois établissements de soins complexes de longue durée. Trois catégories, qui reflètent le rôle du gestionnaire d'unité auprès des membres de la famille des patients d'un centre de soins complexes de longue durée, ont été établies : établir un accueil positif; créer des liens et les entretenir; boucler la boucle. L'incidence des résultats de cette recherche, en matière de pratiques et de recherches à venir, est également présentée.
Phytoestrogen α‐Zearalanol exerts Antiapoptotic Effects in Differentiated PC12 Cells via Oestrogen Receptor α

Our previous studies have demonstrated that phytoestrogen α‐zearalanol (α‐ZAL) possesses potential benefits in alleviating cell apoptotic death just like oestrogen. However, the underlying mechanism is not fully understood. This study was designed to test the hypothesis that the neuroprotective effect of α‐ZAL is mediated by oestrogen receptor (ER) as α‐ZAL owns the benzene ring structure may interact with ER. The present results showed a significant increase in apoptosis in differentiated PC12 cells after a 24‐hr exposure to amyloid β‐peptide fragment 25‐35 (Aβ25‐35), accompanied by decreasing of bcl‐2 expression and increasing bax expression, whereas a pre‐treatment with α‐ZAL ameliorated these changes induced by Aβ25‐35. In addition, the α‐ZAL‐mediated cytoprotection was abrogated by ERα antagonist but not by ERβ antagonist. In summary, these data suggest that α‐ZAL intervenes against Aβ‐induced apoptosis via intersecting bcl‐2‐bax apoptotic pathway in an ERα‐sensitive manner.
A review of one year of British Armed Forces mental health hospital admissions

Objectives The paper provides a review of one year of military Mental Health (MH) hospital admissions. This includes an exploration into demographic trends, differences in clinical opinion and how information gained is used to improve the service and ensure appropriate, cost effective care in the optimum environment. Methods The sample group is entitled military MH hospital admissions from 1 April 2005 to 31 March 2006. Data was collected on questionnaires with SPSS used for the management and analysis of the quantitative data, with the information exposed to descriptive and inferential statistical analysis. Results There were 344 admissions. The paper contains a detailed review of a number of variables. Depression was the most common diagnosis resulting in 112 (33%) hospital admissions and Post Traumatic Stress Disorder accounted for 23 (7%). There were statistically significant differences that may be attributable to gender with more women admitted with depression and more men with alcohol related disorders. The average length of stay was 21 days, with 48% of patients discharged within 3 weeks. 45% of all returns included significant events reporting that highlighted written evidence of good and poor practice. Conclusion This study is part of an extensive monitoring programme of military MH hospital admissions. Depression is the most common MH problem leading to hospital admission. The results indicate that Service-personnel have access to a highly responsive service that provides brief assessment and treatment within a safe therapeutic environment. 45% of returns included significant event information that resulted in policy changes, leading to improved patient care and a better interface with the NHS. Bench-marking, both internally between military Departments of Community Mental Health and externally have improved visibility and self awareness leading to better GP induction programmes, PHC educational seminars and the establishment of MH web-pages. The Armed Forces need an effective MH service that is accessible, readily available, non-stigmatised and which positively advocates a duty of care. The results highlight the importance of further studies regarding depression to ensure that the Armed Forces are in a better position to maximise the use of MH resources.
Medium Moderates the Message. How Users Adjust Their Communication Trajectories to Different Media in Collaborative Task Solving

Rapid development of information and communications technologies (ICT) has triggered profound changes in how people manage their social contacts in both informal and professional contexts. ICT mediated communication may seem limited in possibilities compared to face-to-face encounters, but research shows that puzzlingly often it can be just as effective and satisfactory. We posit that ICT users employ specific communication strategies adapted to particular communication channels, which results in a comparable effectiveness of communication. In order to maintain a satisfactory level of conversational intelligibility they calibrate the content of their messages to a given medium’s richness and adjust the whole conversation trajectory so that every stage of the communication process runs fluently. In the current study, we compared complex task solving trajectories in chat, mobile phone and face-to-face dyadic conversations. Media conditions did not influence the quality of decision outcomes or users’ perceptions of the interaction, but they had impact on the amount of time devoted to each of the identified phases of decision development. In face-to-face contacts the evaluation stage of the discussion dominated the conversation; in the texting condition the orientation-evaluation-control phases were evenly distributed; and the phone condition provided a midpoint between these two extremes. The results show that contemporary ICT users adjust their communication behavior to the limitations and opportunities of various media through the regulation of attention directed to each stage of the discussion so that as a whole the communication process remains effective.
Engineering of high yield production of L‐serine in Escherichia coli

L‐serine is a widely used amino acid that has been proposed as a potential building block biochemical. The high theoretical yield from glucose makes a fermentation based production attractive. In order to achieve this goal, serine degradation to pyruvate and glycine in E. coli MG1655 was prevented by deletion of three L‐serine deaminases sdaA, sdaB, and tdcG, as well as serine hydroxyl methyl transferase (SHMT) encoded by glyA. Upon overexpression of the serine production pathway, consisting of a feedback resistant version of serA along with serB and serC, this quadruple deletion strain showed a very high serine production yield (0.45 g/g glucose) during small‐scale batch fermentation in minimal medium. Serine, however, was found to be highly toxic even at low concentrations to this strain, which lead to slow growth and production during fed batch fermentation, resulting in a serine production of 8.3 g/L. The production strain was therefore evolved by random mutagenesis to achieve increased tolerance towards serine. Additionally, overexpression of eamA, a cysteine/homoserine transporter was demonstrated to increase serine tolerance from 1.6 g/L to 25 g/L. During fed batch fermentation, the resulting strain lead to the serine production titer of 11.7 g/L with yield of 0.43 g/g glucose, which is the highest yield reported so far for any organism. Biotechnol. Bioeng. 2016;113: 807–816. © 2015 Wiley Periodicals, Inc.
A Protection Motivation Theory application to date rape education

Date rape risk communication is a key component of education-based Date Rape Prevention Programs, common across colleges. In such programs, risk assessment in date rape is approached cautiously in order to avoid a tone of “victim blaming. ” Since it is important in the assessment of any risk to understand the surrounding social context of the risky situation and the individual's unique relationship with that social context, this study examines Protection Motivation Theory as it applies to handling the risk of date rape without victim blaming. The paper links individual personality and social contexts with risk communication. The study sample comprised 367 undergraduate women enrolled in a large Southern Public University. The study examines the relationships between dating activity, social competency, and type of information provided with the dependents variables of date rape related protection behavior (intent), belief, and knowledge. A factorial multiple analysis of covariance analysis found that the dependent variables had a significant relationship with aspects of social competency and dating activity. The exposure to varying information about date rape was not significantly related to the dependent variables of date rape-related protection behavior (intent), belief, and knowledge. The identification of social competency and dating activity status as protective factors in this study makes a significant contribution to the practice and research efforts in date rape education.
Acute Termination of Human Atrial Fibrillation by Identification and Catheter Ablation of Localized Rotors and Sources: First Multicenter Experience of Focal Impulse and Rotor Modulation (FIRM) Ablation

FIRM Ablation of Human AF Rotors. Introduction: Catheter ablation of atrial fibrillation (AF) currently relies on eliminating triggers, and no reliable method exists to map the arrhythmia itself to identify ablation targets. The aim of this multicenter study was to define the use of Focal Impulse and Rotor Modulation (FIRM) for identifying ablation targets.