On the structure of acyclic binary relations

We investigate the structure of acyclic binary relations from different points of view. On the one hand, given a nonempty set we study real-valued bivariate maps that satisfy suitable functional equations, in a way that their associated binary relation is acyclic. On the other hand, we consider acyclic directed graphs as well as their representation by means of incidence matrices. Acyclic binary relations can be extended to the asymmetric part of a linear order, so that, in particular, any directed acyclic graph has a topological sorting.This work has been partially supported by the research projects MTM2012-37894-C02-02, TIN2013-47605-P, ECO2015-65031-R, MTM2015-63608-P (MINECO/FEDER), TIN2016-77356-P and the Research Services of the Public University of Navarre (Spain)

Evolutionary conservation of lampbrush-like loops in drosophilids

<p>Abstract</p> <p>Background</p> <p>Loopin-1 is an abundant, male germ line specific protein of <it>Drosophila melanogaster</it>. The polyclonal antibody T53-F1 specifically recognizes Loopin-1 and enables its visualization on the Y-chromosome lampbrush-like loop named kl-3 during primary spermatocyte development, as well as on sperm tails. In order to test lampbrush-like loop evolutionary conservation, extensive phase-contrast microscopy and immunostaining with T53-F1 antibody was performed in other drosophilids scattered along their genealogical tree.</p> <p>Results</p> <p>In the male germ line of all species tested there are cells showing giant nuclei and intranuclear structures similar to those of <it>Drosophila melanogaster </it>primary spermatocytes. Moreover, the antibody T53-F1 recognizes intranuclear structures in primary spermatocytes of all drosophilids analyzed. Interestingly, the extent and conformation of the staining pattern is species-specific. In addition, the intense staining of sperm tails in all species suggests that the terminal localization of Loopin-1 and its orthologues is conserved. A comparison of these cytological data and the data coming from the literature about sperm length, amount of sperm tail entering the egg during fertilization, shape and extent of both loops and primary spermatocyte nuclei, seems to exclude direct relationships among these parameters.</p> <p>Conclusion</p> <p>Taken together, the data reported strongly suggest that lampbrush-like loops are a conserved feature of primary spermatocyte nuclei in many, if not all, drosophilids. Moreover, the conserved pattern of the T53-F1 immunostaining indicates that a Loopin-1-like protein is present in all the species analyzed, whose localization on lampbrush-like loops and sperm tails during spermatogenesis is evolutionary conserved.</p

Fighting Misconceptions to Improve Compliance with Influenza Vaccination among Health Care Workers: An Educational Project

The compliance with influenza vaccination is poor among health care workers (HCWs) due to misconceptions about safety and effectiveness of influenza vaccine. We proposed an educational prospective study to demonstrate to HCWs that influenza vaccine is safe and that other respiratory viruses (RV) are the cause of respiratory symptoms in the months following influenza vaccination. 398 HCWs were surveyed for adverse events (AE) occurring within 48 h of vaccination. AE were reported by 30% of the HCWs. No severe AE was observed. A subset of 337 HCWs was followed up during four months, twice a week, for the detection of respiratory symptoms. RV was diagnosed by direct immunofluorescent assay (DFA) and real time PCR in symptomatic HCWs. Influenza A was detected in five episodes of respiratory symptoms (5.3%) and other RV in 26 (27.9%) episodes. The incidence density of influenza and other RV was 4.3 and 10.8 episodes per 100 HCW-month, respectively. The educational nature of the present study may persuade HCWs to develop a more positive attitude to influenza vaccination

Microarray identifies ADAM family members as key responders to TGF-β1 in alveolar epithelial cells

The molecular mechanisms of Idiopathic Pulmonary Fibrosis (IPF) remain elusive. Transforming Growth Factor beta 1(TGF-β1) is a key effector cytokine in the development of lung fibrosis. We used microarray and computational biology strategies to identify genes whose expression is significantly altered in alveolar epithelial cells (A549) in response to TGF-β1, IL-4 and IL-13 and Epstein Barr virus. A549 cells were exposed to 10 ng/ml TGF-β1, IL-4 and IL-13 at serial time points. Total RNA was used for hybridisation to Affymetrix Human Genome U133A microarrays. Each in vitro time-point was studied in duplicate and an average RMA value computed. Expression data for each time point was compared to control and a signal log ratio of 0.6 or greater taken to identify significant differential regulation. Using normalised RMA values and unsupervised Average Linkage Hierarchical Cluster Analysis, a list of 312 extracellular matrix (ECM) proteins or modulators of matrix turnover was curated via Onto-Compare and Gene-Ontology (GO) databases for baited cluster analysis of ECM associated genes. Interrogation of the dataset using ontological classification focused cluster analysis revealed coordinate differential expression of a large cohort of extracellular matrix associated genes. Of this grouping members of the ADAM (A disintegrin and Metalloproteinase domain containing) family of genes were differentially expressed. ADAM gene expression was also identified in EBV infected A549 cells as well as IL-13 and IL-4 stimulated cells. We probed pathologenomic activities (activation and functional activity) of ADAM19 and ADAMTS9 using siRNA and collagen assays. Knockdown of these genes resulted in diminished production of collagen in A549 cells exposed to TGF-β1, suggesting a potential role for these molecules in ECM accumulation in IPF

Functional assessment of older patients in the emergency department: comparison between standard instruments, medical records and physicians' perceptions

BACKGROUND: We evaluated the accuracy of physician recognition of functional status impairment in older emergency departments (ED) patients. In particular, we evaluated the accuracy of medical records (a comparison of the information in the medical record with the functional status based on proxy interviews), and the accuracy of physician knowledge (a comparison of the information obtained from the responsible physician with the functional status based on proxy interviews). METHODS: Cross-sectional study on 101 frail older patients selected at random from among those attending ED, their ED physicians, and respondents. The study was conducted at ED in four general university teaching hospitals in a city, from July through November 2003. Functional data shown on patients' medical records were compared against functional data obtained from respondents (family members), using Kendall's Tau-b statistic. In addition patients' Katz Indices (which assesses six basic activities of daily living – basic ADL) based on interviews with ED physicians were compared against those obtained from respondents, using the coefficient of concordance weighted kappa (κ). Each patient and his respondent were paired with a single physician. RESULTS: The correlation between information on dependence for basic ADL obtained from medical records and that furnished by respondents, was 0.41 (95% CI 0.27–0.55). Concordance between the respective Katz Indices obtained from physicians and respondents was 0.47 (95% CI 0.38–0.57). CONCLUSION: Older subjects' functional status is not properly assessed by emergency department physicians

HIV-1 Tat protein alter the tight junction integrity and function of retinal pigment epithelium: an in vitro study

<p>Abstract</p> <p>Background</p> <p>How HIV-1 enter into the eyes remains obscure. We postulated that HIV-1 Tat protein can alter the expression of specific tight-junction proteins and disturb the blood retinal barrier, and contributes to HIV trafficking into the eyes. This study is to determine the effects of HIV-1 Tat proteins on the barrier function and tight-junction protein expression of retinal pigment epithelial cell (RPE).</p> <p>Methods</p> <p>A human RPE cell line (D407) cultured on microporous filter-supports was used. After treating with HIV-1 Tat protein, transepithelial electrical resistance (TER) of confluent RPE cells was measured by epithelial voltmeter. The permeability of the RPE cells to sodium fluorescein was measured. The expressions of the occludin and claudins were determined by real-time polymerase chain reaction, immunofluorescence, and Western blot analysis. Activation of ERK1/2 was detected by Western blot analysis with specific antiphospho protein antibodies. NF-κB DNA binding activity was determined by transcription factor assay. Specific pharmacologic inhibitors directed against the MAPKs were used to analyze the signaling involved in barrier destruction of RPE cells exposed to HIV-1 Tat.</p> <p>Results</p> <p>Treating cultured human retinal pigment epithelial cells with 100 nM Tat for 24 hours increased the permeability and decreased the TER of the epithelial monolayer. HIV-1 Tat also disrupted and downregulated the tight-junction proteins claudin-1, claudin-3, and claudin-4 in these cells, whereas claudin-2 was upregulated, and the expression of occludin was unaffected. HIV-1 Tat protein also induced activation of ERK1/2 and NF-κB. HIV-1 Tat protein induced barrier destruction, changes in expression of TJs, and activation of ERK1/2 and NF-κB were abrogated by inhibitor of ERK1/2 and NF-κB.</p> <p>Conclusion</p> <p>HIV-1 Tat protein causes increases in the paracellular permeability of RPE cells in vitro concomitant with changes in expression of certain transmembrane proteins associated with the tight junction. The effects of HIV-1 Tat on barrier function of the RPE may be mediated by ERK MAPK and NF-κB activation, which may represent potential targets for novel therapeutic approaches for the retinopathy induced by HIV infection.</p

Vascular Collagen Type-IV in Hypertension and Cerebral Small Vessel Disease.

BACKGROUND: Cerebral small vessel disease (SVD) is common in older people and causes lacunar stroke and vascular cognitive impairment. Risk factors include old age, hypertension and variants in the genes COL4A1/COL4A2 encoding collagen alpha-1(IV) and alpha-2(IV), here termed collagen-IV, which are core components of the basement membrane. We tested the hypothesis that increased vascular collagen-IV associates with clinical hypertension and with SVD in older persons and with chronic hypertension in young and aged primates and genetically hypertensive rats. METHODS: We quantified vascular collagen-IV immunolabeling in small arteries in a cohort of older persons with minimal Alzheimer's pathology (N=52; 21F/31M, age 82.8±6.95 years). We also studied archive tissue from young (age range 6.2-8.3 years) and older (17.0-22.7 years) primates (M mulatta) and compared chronically hypertensive animals (18 months aortic stenosis) with normotensives. We also compared genetically hypertensive and normotensive rats (aged 10-12 months). RESULTS: Collagen-IV immunolabeling in cerebral small arteries of older persons was negatively associated with radiological SVD severity (ρ: -0.427, P=0.005) but was not related to history of hypertension. General linear models confirmed the negative association of lower collagen-IV with radiological SVD (P<0.017), including age as a covariate and either clinical hypertension (P<0.030) or neuropathological SVD diagnosis (P<0.022) as fixed factors. Reduced vascular collagen-IV was accompanied by accumulation of fibrillar collagens (types I and III) as indicated by immunogold electron microscopy. In young and aged primates, brain collagen-IV was elevated in older normotensive relative to young normotensive animals (P=0.029) but was not associated with hypertension. Genetically hypertensive rats did not differ from normotensive rats in terms of arterial collagen-IV. CONCLUSIONS: Our cross-species data provide novel insight into sporadic SVD pathogenesis, supporting insufficient (rather than excessive) arterial collagen-IV in SVD, accompanied by matrix remodeling with elevated fibrillar collagen deposition. They also indicate that hypertension, a major risk factor for SVD, does not act by causing accumulation of brain vascular collagen-IV

Wellbeing, mental health knowledge and caregiving experiences of siblings of people with psychosis, compared to their peers and parents: An exploratory study

Purpose The wellbeing and caregiving experiences of family carers supporting people with psychosis has garnered increasing interest. Evidence indicates that the burden of caregiving can adversely impact on parents’ wellbeing, few studies have investigated whether this is also the case for siblings, who often take on caregiving responsibilities. This exploratory study investigated the wellbeing, mental health knowledge, and appraisals of caregiving in siblings of individuals with psychosis. Method Using a cross-sectional design, 90 siblings completed three validated questionnaires: Warwick–Edinburgh Mental Wellbeing Scale (WEMWBS), Mental Health Knowledge Schedule (MAKS), and Experience of Caregiving Inventory (ECI). Data obtained were compared to general population norms and parent-carers’ scores. Multi-variable regression analyses were conducted to examine relationships between questionnaire scores and demographic characteristics including age, sex, birth order, marital status, accommodation and educational level. Results Siblings, especially sisters, had significantly poorer mental wellbeing, compared to normative scores. Conversely, they had better mental health knowledge. Siblings and parent-carers had comparable high levels of negative appraisals of caregiving experiences, but siblings reported more satisfaction with personal experiences and relationships. Education level was a significant predictor for better mental health knowledge; there were no other relationships between siblings’ demographic factors and outcomes. Conclusion Study findings suggest that siblings have overlapping as well as distinct needs, compared to parent-carers. Further research is required to better understand siblings’ experiences so as to inform development of targeted interventions that enhance wellbeing and caregiving capacity