Miracle-dz/UniFAR-FTUs huggingface dataset:
Adenylate cyclase in£uences¢lamentoushaemagglutinin- mediatedattachmentofBordetella pertussis to epithelial alveolar cells

Attachment to epithelial cells in the respiratory tract is a key event in Bordetella pertussis colonization. Filamentous haemagglutinin (FHA) is an important virulence factor mediating adhesion to host cells. In this study, the relevance of the interaction between FHA and adenylate cyclase toxin (ACT) during bacterial attachment was investigated. Mutants lacking either FHA or ACT showed significantly decreased adherence to epithelial respiratory cells. The use of several ACT-specific monoclonal antibodies and antiserum showed that the decrease in attachment of strains lacking ACT expression could not be explained by the adhesin-like activity of ACT, or a change of any of the biological activities of ACT. Immunoblot analysis showed that the lack of ACTexpression did not interfere with FHA localization. An heparin-inhibitable carbohydrate-binding site is crucial in the process of FHA-mediated bacterial binding to epithelial cells. In the presence of heparin attachment of wild-type B. pertussis, but not of the isogenic ACT defective mutant, to epithelial cells was significantly decreased. These results suggest that ACTenhances the adhesive functions of FHA, and modifies the performance of the FHA heparin-inhibitable carbohydrate binding site. We propose that the presence of ACT in the outer membrane of B. pertussis to play a role in the functionality of FHA.
Evidence for Bluegill Spawning Plasticity Obtained by Disentangling Complex Factors Related to Recruitment

Fishes can exhibit many forms of plasticity to maximize fitness. However, limited information exists on the ability of freshwater fish to adjust spawning behavior and characteristics (e.g., timing, duration, magnitude of spawning events) to minimize mortality of recruits and ultimately maximize fitness. We wanted to test the life history hypothesis for bluegill (Lepomis macrochirus) (i.e., opportunistic strategy) utilizing existing literature and results from our study to further evaluate the potential for spawning plasticity in this species. Our objective was to identify bluegill recruitment bottlenecks (i.e., periods of high mortality) and factors associated with these events in a single lake during 7 consecutive years. Bluegills exhibited shorter spawning durations and fewer spawning pulses (i.e., peaks in larval production) compared with bluegill in previous studies. Late-hatched (compared with early-hatched) bluegills consistently contributed the most to the fall juvenile population; these recruitment patterns were primarily attributed to biotic drivers. Our study suggests that bluegill could exhibit spawning plasticity and extends our current understanding of adaptations that are potentially capable of increasing fitness for a freshwater fish species under a wide range of environmental conditions and uncertainty. Résumé : Les poissons peuvent présenter différentes formes de plasticité leur permettant de maximiser leur aptitude. Peu de renseignements sont toutefois disponibles sur la capacité des poissons d'eau douce d'ajuster leur comportement de frai et les caractéristiques de ce dernier (p. ex. moment, durée, magnitude des évènements de frai) afin de minimiser la mortalité des recrues et, au final, maximiser leur aptitude. Nous voulions tester l'hypothèse du cycle biologique (c.-à-d. stratégie opportuniste) pour le crapet arlequin (Lepomis macrochirus) à la lumière d'études existantes et des résultats de notre étude pour évaluer plus en détail le potentiel de plasticité du frai chez cette espèce. L'objectif consistait à cerner les goulots d'étranglement en ce qui concerne le recrutement de crapets arlequins (c.-à-d. périodes de mortalité élevée) et les facteurs associés à ces évènements dans un seul lac pendant 7 années consécutives. Comparativement aux études antérieures, les crapets arlequins présentaient des durées de frai plus courtes et moins de pointes de frai (ou de production de larves). La contribution à la population juvénile automnale des crapets arlequins à éclosion tardive était uniformément plus importante que celle des individus à éclosion précoce, ces motifs de recrutement étant principalement attribuables à des facteurs biotiques. L'étude donne à penser que les crapets arlequins pourraient présenter une plasticité de frai et elle élargit la compréhension actuelle des adaptations pouvant potentiellement accroître l'aptitude d'une espèce de poissons dulcicoles pour un vaste éventail de conditions ambiantes et de niveaux d'incertitude. [Traduit par la Rédaction]
Human Trafficking and Labour Exploitation in the Casual Construction Industry: An Analysis of Three Major Investigations in the UK Involving Irish Traveller Offending Groups

Human trafficking and modern slavery are routinely framed as key threats facing society. Despite increased media, policy, and practitioner attention the evidence base remains underdeveloped. The numerous knowledge gaps include a lack of empirical studies and research into labour trafficking. Since labour trafficking is a complex and varied phenomenon, we chose to explore one subset of it in a systematic, detailed, and empirical fashion. Our focus was exploitation in the casual construction industry in the UK perpetrated by Irish Traveller offending groups. We used hard-to-reach data from three major police investigations, namely operational case files and interviews with senior investigating officers. Taking a qualitative approach, we disentangled behaviours and dynamics across three major stages in the trafficking process: recruitment, control, and exploitation. We identified key challenges associated with investigating this crime. In discussing our study’s implications for research, policy, and practice, we also include officers’ recommendations for future cases.
FETAL OUTCOME OF PREGNANCIES IN WOMEN AT THE EXTREMES OF MATERNAL AGE

Background: Extremes of maternal age adversely affect pregnancy outcomes . Teenage pregnancy is regarded as a serious public health problem and often occurs in the context of poor social support and maternal well-being. Teenage pregnancy is known to be associated with adverse pregnancy outcomes such as preterm births, low birth weight deliveries and increased risk of caesarean delivery. Methods: A hospital based prospective study carried out in the Department of Obstetrics and Gynaecology from October 2013 to September 2015 at Owaisi hospital and research centre and Princess Esra Hospital, a tertiary care centre, Deccan College of medical sciences, Hyderabad. Results: Among 8640 antenatal patients who delivered during the 24 months period i.e October 2013 to September 2015 at the hospital out of these 241(2.8%) were teenage primigravida aged 15 to 19 yrs. Conclusions: In India, 10.3% of the female population belongs to the age group of l5-19 years. [19] In 1997, the age specific fertility rate was found to be 52.5 live births per 1000 rural women aged between 15-19 years. [42] Over the years, there has not been much improvement in the country’s scenario as reported by the National Family Health Surveys.
Liquidity Risks Models in Jordanian Commercial Banks

The relatively large size of the commercial banks in Jordan compared to other sectors in the economy as well as the turmoil in the MENA region is the motivation of this study analysed the impact of internal bank factors such as profitability, capital, credit, size and quality of management on liquidity risk for thirteen Jordanian commercial banks while controlling for the regulatory and macroeconomic environment using a panel data model. The econometric results show that profitability has a positive impact on liquidity risk whilst the existence of an efficient management has a negative impact on liquidity risk. Finally, the impact of capital and credit on liquidity risk had an ambiguous effect due to the interactions between the different factors. The breadth of commercial banks’ activities in Jordan as regards financing most of the economic sectors in the country through their role as financial intermediaries marks the importance of shielding them from liquidity risks.
FULL COST ACCOUNTING ON EXISTING AND FUTURE MUNICIPAL SOLID WASTE MANAGEMENT FACILITIES IN GREECE

ABSTRACT In this work, we performed a detailed full cost accounting for 7 types of existing and planned municipal solid waste management facilities (sanitary landfills, anaerobic digestion, biodrying, incineration, aerobic mechanical and biological, material recovery and waste transfer stations) in Greece. We used investment costs (IC), operating costs (OC) and future (restoration) costs (FC) to calculate the actual total unit cost (€/t) of the above types of facilities in 2012 prices. Mathematical cost functions were developed to describe the total cost (€/t) as a function of the MSW input rate (t/y). Actual data from several operating facilities in Greece were used, as well as estimated costs from facilities that are planned or are under construction in Greece. Results showed that the sanitary landfills follow the economy of scale with an average total unit cost of €45/t. The unit cost of the planned anaerobic digestion facilities ranged from €50 to €104/t. The biodrying facilities’ unit cost ranged from €48 to €138/t, whilst the sole MSW incineration facility was found to have a unit cost of €115/t. Aerobic MBT facilities did not follow the economy of scale. The average total unit cost from 23 MRFs was €32/t. The depreciated investment cost of 18 waste transfer stations (WTS) ranged from €0.5/t to €28/t.
Conjunctival Melanoma: Update on Genetics, Epigenetics and Targeted Molecular and Immune-Based Therapies

Purpose: To present the molecular mechanisms involved in the pathogenesis of conjunctival melanoma (CM) and review the existing literature on targeted molecular inhibitors as well as immune checkpoint inhibitors for the management of locally advanced and metastatic disease. Methods: A comprehensive review of the literature was performed using the keywords “conjunctival melanoma”, “immune checkpoint inhibitors”, “BRAF inhibitors”, “MEK inhibi-tors”, “CTLA4 inhibitors”, “PD1 inhibitors”, “c-KIT mutations”, “BRAF mutations”, “NRAS mutations”, “dabrafenib”, “trametinib”, “vemurafenib”, “ipilimumab”, “pembrolizumab”, and “nivolumab”. A total of 250 articles were reviewed and 120 were included in this report. Results: Mutations of mediators in the MAP kinase pathway, such as RAS, BRAF, MEK and ERK, and mutations of the PI3K/AKT/mTOR pathway play a major role in the pathogenesis of conjunctival melanoma. In addition, alterations of c-KIT, NF1, TERT, chemokine receptors as well as chromosomal copy number alterations and micro RNAs are thought to have a causative association with CM development. Targeted molecular inhibitors, such as BRAF and MEK inhibitors, are currently being implemented in the therapy of BRAF -mutated CM. Furthermore, immune checkpoint PD-1 and CTLA4 inhibitors with favorable clinical outcomes in the treatment of cutaneous melanoma have increased recurrence-free survival and reduced metastatic spread in CM cases. Conclusion: The complex molecular mechanisms that contribute to the development of CM can be targeted both by molecular inhibitors of oncogenic pathways as well as immune checkpoint inhibitors in order to halt progression of the disease and increase survival.
Electrophysiological heterogeneity in large populations of rabbit ventricular cardiomyocytes

Abstract Aims Cardiac electrophysiological heterogeneity includes: (i) regional differences in action potential (AP) waveform, (ii) AP waveform differences in cells isolated from a single region, (iii) variability of the contribution of individual ion currents in cells with similar AP durations (APDs). The aim of this study is to assess intra-regional AP waveform differences, to quantify the contribution of specific ion channels to the APD via drug responses and to generate a population of mathematical models to investigate the mechanisms underlying heterogeneity in rabbit ventricular cells. Methods and results APD in ∼50 isolated cells from subregions of the LV free wall of rabbit hearts were measured using a voltage-sensitive dye. When stimulated at 2 Hz, average APD90 value in cells from the basal epicardial region was 254 ± 25 ms (mean ± standard deviation) in 17 hearts with a mean interquartile range (IQR) of 53 ± 17 ms. Endo-epicardial and apical-basal APD90 differences accounted for ∼10% of the IQR value. Highly variable changes in APD occurred after IK(r) or ICa(L) block that included a sub-population of cells (HR) with an exaggerated (hyper) response to IK(r) inhibition. A set of 4471 AP models matching the experimental APD90 distribution was generated from a larger population of models created by random variation of the maximum conductances (Gmax) of 8 key ion channels/exchangers/pumps. This set reproduced the pattern of cell-specific responses to ICa(L) and IK(r) block, including the HR sub-population. The models exhibited a wide range of Gmax values with constrained relationships linking ICa(L) with IK(r), ICl, INCX, and INaK. Conclusion Modelling the measured range of inter-cell APDs required a larger range of key Gmax values indicating that ventricular tissue has considerable inter-cell variation in channel/pump/exchanger activity. AP morphology is retained by relationships linking specific ionic conductances. These interrelationships are necessary for stable repolarization despite large inter-cell variation of individual conductances and this explains the variable sensitivity to ion channel block.
Joy, Edward J.M. and Stein, Alexander J. and Young, Scott D. and Ander, E. Louise and Watts, Michael J. and Broadley, Martin R. (2015) Zinc-enriched fertilisers as a potential public health intervention in Africa. Plant

16 17 Background 18 In this review, we examine the potential of Zn-enriched fertilisers to alleviate human dietary Zn 19 deficiency. The focus is on 10 African countries where dietary Zn supply is low and where fertiliser 20 subsidies are routinely deployed on cereal crops. 21 22 Scope 23 Dietary Zn supply and deficiency prevalence were quantified from food supply and composition data. 24 Typical effects of soil (granular) and foliar Zn applications on Zn concentrations in maize (Zea mays 25 L.), rice (Oryza sativa L.) and wheat (Triticum aestivum L.) grains were based on a systematic 26 literature review. Reductions in disease burdens attributable to Zn deficiency and cost-effectiveness 27 were estimated using a disability-adjusted life years (DALYs) approach. 28 29 Conclusions 30 Baseline Zn supply in 2009 ranged from 7.1 (Zambia) to 11.9 (Mali) mg capita -1 d -1 ; prevalence of Zn 31 deficiency ranged from 24 (Nigeria) to 66 % (Zambia). In reviewed studies, soil Zn application led to 32 an increase in median Zn concentration in maize, rice and wheat grains of 23, 7 and 19 %; foliar 33 application led to increases of 30, 25 and 63 %. Enriching granular fertilisers within current subsidy 34 schemes would be most effective in Malawi, reducing DALYs lost due to Zn deficiency by 10 %. The 35 cost per DALY saved ranged from US$ 624 to 5,893 via granular fertilisers and from US$ 46 to 347 36 via foliar fertilisers. Foliar applications are likely to be more cost effective than soil applications due 37 to fixation of Zn in the soil but may be more difficult to deploy. Zinc fertilisation is likely to be less 38 cost-effective than breeding in the longer term although other micronutrients such as selenium could 39 be incorporated. 40 41
Immunostimulatory- Fusogenic and Conventional Liposome Adjuvants Induce Qualitatively and Quantitatively Distinct Innate and Adaptive Immune Responses

An ideal adjuvant should possess both immunostimulatory and antigen delivery properties for simultaneous induction of innate and adaptive immune response to clear pathogens from host. The majority of pharmaceutical based adjuvants currently being used are particle based delivery systems, such as liposome formulations. However, the mechanism of their action is largely unknown. To identify the regulatory gene cascade that triggers the innate immune response following liposome adjuvant injection, we applied microarray based transcriptional profiling of tissue sites (muscle and peritoneum) of mouse injected with conventional (CL) and immunostimulatory fusogenic liposomes (IFL). While CL and IFL induced large number of shared innate immune genes, IFL activated quantitatively and qualitatively stronger immune response than CL. IFL induced upregulation of pro-inflammatory response genes and triggered a rapid influx of antigen presenting cells (APCs) as compared to CL. Comparison of gene interaction network revealed several fold increase of gene interactions at the injection site with IFL as compared to CL. The induction of innate response by IFL was correlated to strong adaptive response against encapsulated antigen ovalbumin (OVA) indicated by strong T cell proliferation and cytokine production. Notably, CL induced a biased Th2 response whereas IFL favored a predominant Th1 or mixed of Th1/ Th2 response. Our data indicate that IFL induced quantitatively and qualitatively distinct and strong innate immune signals which correlated to strong adaptive immune response. These results provide novel insights into understanding the mechanism of action of liposomes and may be utilized for development of improved liposome based vaccines.
Rapid Publication Normalization of Raised Sodium Absorption and Raised Calcium-mediated Chloride Secretion by Adenovirus-mediated Expression of Cystic Fibrosis Transmembrane Conductance Regulator in Primary Human Cystic Fibrosis Airway Epithelial Cells

Cystic fibrosis airway epithelia exhibit a spectrum of ion transport properties that differ from normal, including not only defective cAMP-mediated Clsecretion, but also increased Na+ absorption and increased Ca2"-mediated Clsecretion. In the present study, we examined whether adenovirus-mediated (Ad5) transduction of CFTR can correct all of these CF ion transport abnormalities. Polarized primary cultures of human CF and normal nasal epithelial cells were infected with Ad5-CBCFTR at an moi (104) which transduced virtually all cells or Ad5-CMV lacZ as a control. Consistent with previous reports, Ad5-CBCFTR, but not Ad5CMV lacZ, corrected defective CF cAMP-mediated Cl secretion. Basal Na + transport rates (basal I,q) in CF airway epithelial sheets (-78.5±9.8 puA/cm2) were reduced to levels measured in normal epithelial sheets (-30.0±2.0 pAA/cm2) by Ad5-CBCFTR (-36.9±4.8 1uA/cm2), but not Ad5CMV lacZ ( -65.8±6.1 IAA/cm2). Surprisingly, a signfficant reduction in AIq in response to ionomycin, a measure of Ca2+-mediated Clsecretion, was observed in CFTR-expressing (corrected) CF epithelial sheets (-6.9±11.8 ,uA/ cm2) when compared to uninfected CF epithelial sheets (-76.2±15.1 puA/cm2). Dose response effects of AdSCBCFTR on basal Na+ transport rates and Ca2+-mediated Clsecretion suggest that the mechanism of regulation of these two ion transport functions by CFTR may be different. In conclusion, efficient transduction of CFTR corrects hyperabsorption of Na + in primary CF airway epithelial cells and restores Ca2+-mediated Clsecretion to levels observed in normal airway epithelial cells. Moreover, assessment of these ion transport abnormalities may represent important endpoints for testing the efficacy of gene therapy for cystic Address correspondence to Larry G. Johnson, Division of Pulmonary Diseases and Critical Care Medicine, CB#7020, 724 Bumett-Womack Bldg. , The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7020. Phone: 919-966-2531; FAX: 919-966-7524. Received for publication 31 May 1994 and in revisedform 16 November 1994. fibrosis. (J. Clin. Invest. 1995. 95:1377-1382).
Reconstructing solar magnetic fields from historical observations : IV. Testing the reconstruction method

Abstract Aims. The evolution of the photospheric magnetic field has only been regularly observed since the 1970s. The absence of earlier observations severely limits our ability to understand the long-term evolution of solar magnetic fields, especially the polar fields that are important drivers of space weather. Here, we test the possibility to reconstruct the large-scale solar magnetic fields from Ca II K line observations and sunspot magnetic field observations, and to create synoptic maps of the photospheric magnetic field for times before modern-time magnetographic observations. Methods. We reconstructed active regions from Ca II K line synoptic maps and assigned them magnetic polarities using sunspot magnetic field observations. We used the reconstructed active regions as input in a surface flux transport simulation to produce synoptic maps of the photospheric magnetic field. We compared the simulated field with the observed field in 1975−1985 in order to test and validate our method. Results. The reconstruction very accurately reproduces the long-term evolution of the large-scale field, including the poleward flux surges and the strength of polar fields. The reconstruction has slightly less emerging flux because a few weak active regions are missing, but it includes the large active regions that are the most important for the large-scale evolution of the field. Although our reconstruction method is very robust, individual reconstructed active regions may be slightly inaccurate in terms of area, total flux, or polarity, which leads to some uncertainty in the simulation. However, due to the randomness of these inaccuracies and the lack of long-term memory in the simulation, these problems do not significantly affect the long-term evolution of the large-scale field.
AFLUID January 47/1

Meng, Xianmin, and W. Brian Reeves. Effects of chloride channel inhibitors on H2O2-induced renal epithelial cell injury. Am. J. Physiol. Renal Physiol. 278: F83–F90, 2000. — Oxidative stress contributes to renal epithelial cell injury in certain settings. Chloride influx has also been proposed as an important component of acute renal epithelial cell injury. The present studies examined the role of Cl2 in H2O2-induced injury to LLC-PK1 renal epithelial cells. Exposure of LLCPK1 cells to 1 mM H2O2 resulted in the following: depletion of intracellular ATP content; DNA damage; lipid peroxidation; and a loss of membrane integrity to both small molecules, e.g., trypan blue, and macromolecules, e.g., lactate dehydrogenase (LDH), and cell death. Substitution of Cl2 by isethionate or the inclusion of certain Cl2 channel blockers, e.g., diphenylamine-2-carboxylate (DPC), 5-nitro-2-(3-phenylpropylamino)· benzoate (NPPB), and niflumic acid, prevented the H2O2induced loss of membrane integrity to LDH. In addition, the H2O2-induced loss of membrane integrity was prevented by raising the osmolality of the extracellular solutions, by depletion of cell ATP, and by inhibitors of volume-sensitive Cl2 channels. However, these maneuvers did not prevent the H2O2-induced permeability to small molecules or H2O2induced ATP depletion, DNA damage, lipid peroxidation, or cell death. These results support the view that volumesensitive Cl2 channels play a role in the progressive loss of cell membrane integrity during injury.