Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct Immune Responses in Resistant and Susceptible Strains of Mice during Neurovirulent Alphavirus Encephalomyelitis

ABSTRACT Susceptibility to alphavirus encephalomyelitis is dependent on a variety of factors, including the genetic background of the host. Neuroadapted Sindbis virus (NSV) causes uniformly fatal disease in adult C57BL/6 (B6) mice, but adult BALB/c (Bc) mice recover from infection. In B6 mice, fatal encephalomyelitis is immune mediated rather than a direct result of virus infection. To identify the immunological determinants of host susceptibility to fatal NSV-induced encephalomyelitis, we compared virus titers and immune responses in adult B6 and Bc mice infected intranasally with NSV. B6 mice had higher levels of virus replication, higher levels of type I interferon (IFN), and slower virus clearance than did Bc mice. B6 mice had more neuronal apoptosis, more severe neurologic disease, and higher mortality than Bc mice. B6 mice had more infiltration of inflammatory cells and higher levels of IL1b, IL-6, TNFa, Csf2, and CCL2 mRNAs and interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), IFN-γ, and C-C motif ligand 2 (CCL2) protein in brains than Bc mice. However, Bc mice had more brain antibody at day 7 and a higher percentage of CD4+ T cells. CD4+ T cells in the brains of Bc mice included fewer Th17 cells and more regulatory T cells (Tregs) producing IL-10 than B6 mice, accompanied by higher levels of Il2 and Cxcl10 mRNAs. In the absence of IL-10, resistant Bc mice became susceptible to fatal encephalomyelitis after NSV infection. These studies demonstrate the importance of the immune response and its regulation in determining host survival during alphavirus encephalomyelitis. IMPORTANCE Mosquito-borne alphavirus infections are an important cause of encephalomyelitis in humans. The severity of disease is dependent both on the strain of the virus and on the age and genetic background of the host. A neurovirulent strain of Sindbis virus causes immune-mediated fatal encephalomyelitis in adult C57BL/6 mice but not in BALB/c mice. To determine the host-dependent immunological mechanisms underlying the differences in susceptibility between these two strains of mice, we compared their immune responses to infection. Resistance to fatal disease in BALB/c mice was associated with better antibody responses, more-rapid virus clearance, fewer Th17 cells, and more-potent regulatory T cell responses than occurred in susceptible C57BL/6 mice. In the absence of interleukin-10, a component of the regulatory immune response, resistant mice became susceptible to lethal disease. This study demonstrates the importance of the immune response and its regulation for host survival during alphavirus encephalomyelitis.
Targeting and Trafficking of the Human Thiamine Transporter-2 in Epithelial Cells*

Humans lack biochemical pathways for thiamine synthesis, so cellular requirements are met via specific carrier-mediated uptake pathways. Two proteins from the solute carrier SLC19A gene family have been identified as human thiamine transporters (hTHTRs), SLC19A1 (hTHTR1) and SLC19A2 (hTHTR2). Both of these transporters are co-expressed but are differentially targeted in polarized cell types that mediate vectorial thiamine transport (e.g. renal and intestinal epithelia). It is important to understand the domain structure of these proteins, namely which regions within the polypeptide sequence are important for physiological delivery to the cell surface, in order to understand the impact of clinically relevant mutations on thiamine transport. Here we have characterized the mechanisms regulating hTHTR2 distribution by using live cell imaging methods that resolve the targeting and trafficking dynamics of full-length hTHTR2, a series of hTHTR2 truncation mutants, as well as chimeras comprising the hTHTR1 and hTHTR2 sequence. We showed the following: (i) that the cytoplasmic COOH-tail of hTHTR2 is not essential for apical targeting in polarized cells; (ii) that delivery of hTHTR2 to the cell surface is critically dependent on the integrity of the transmembrane backbone of the polypeptide so that minimal truncations abrogate cell surface expression of hTHTR2; and (iii) video rate images of hTHTR2-containing intracellular vesicles displayed rapid bi-directional trafficking events to and from the cell surface impaired by microtubule-disrupting but not microfilament-disrupting agents as well as by overexpression of the dynactin subunit dynamitin (p50). Finally, we compared the behavior of hTHTR2 with that of hTHTR1 and the human reduced folate carrier (SLC19A1) to underscore commonalities in the cell surface targeting mechanisms of the entire SLC19A gene family.
Rodent Immunohistochemistry

Immunohistochemistry (IHC) is a common adjunct in pathology for morphologic diagnosis, research pathology, and studying the pathogenesis of the disease. Proper technique and interpretation of an immunohistochemistry assay is of utmost importance. A variety of problems, including the presence of artifacts (nonspecific background or other staining problems) and the differentiation between nonspecific and specific staining, commonly occur. It is essential that antibody quality and IHC technique be optimized. We review the histologic patterns of specific and nonspecific staining after using IHC techniques, as well as basic troubleshooting procedures, and provide some examples of nonspecific staining and other artifacts especially in formalin-fixed, paraffin-embedded tissues (FFPE) of mice.
Good Publication Practice As A Prerequisite for Comparable Enzyme Data?

Systems level investigation of genomic and proteomic scale information requires incomparably higher demands for data quality than in previous decades. Truly integrated databases that deal with heterogeneous data need to be developed to be able to retrieve properties of genes, for kinetics of enzymes, for behaviour of complex networks and for the analysis and modelling of complex biological processes. Despite the fast paced global efforts in biological systems research, the current analyses are limited by the lack of available systematic collections of comparable functional enzyme data. Besides its reliability, these data have to provide defined minimum experimental information, they must be available from the literature along with their accepted enzyme names, and must be as comprehensive as possible. However, the reality reveals a different picture: the quality of experimental data of enzymes is insufficient for the needs of systems level investigations. A 2003 founded working group, called STRENDA, recently published suggestions which intend both to improve the quality of reporting functional enzyme data and to support the comparability of inter alia enzyme kinetics for their application in the in silico investigation of biological systems.
Knowledge gatekeepers and technology districts development: a system dynamics modelling

This paper investigates the role, played by a specific economic actor, namely the knowledge gatekeeper, to improve the technology districts' innovative capability. In particular, a system dynamics model is developed both to analyse the knowledge relationships established by the gatekeeper with the district's actors and to describe how these relationships can affect the development of the whole district. These relationships are analysed according to a proximity-based approach, based on the notions of organisational and Technological Proximity (TP). Finally, a simulation is provided to study the influence of the two proximity dimensions between the gatekeeper and the local actors on the technological knowledge creation and, then, on the district innovative capability.
Use of an ipb-lux Fusion To Study Regulation of the Isopropylbenzene Catabolism Operon of Pseudomonas putida RE204 and To Detect Hydrophobic Pollutants in the Environment

A DNA segment involved in the regulation of the isopropylbenzene (cumene) catabolism operon (ipb) of plasmid pRE4 from Pseudomonas putida RE204 and the Vibrio fischeri luciferase genes, luxCDABE, were used to create an ipbRo/pA(prm1)-luxCDABE reporter fusion plasmid, pOS25. Escherichia coli HMS174(pOS25) produces light in the presence of inducers of the ipb operon. These inducers were shown to be hydrophobic compounds and to include monoalkylbenzenes, substituted benzenes and toluenes, some alkanes and cycloalkanes, chlorinated solvents, and naphthalenes. Complex hydrocarbon mixtures, such as gasoline, diesel fuel, jet fuels (JP-4 and JP-5), and creosote, were also inducers of ipb-lux. Bacteria carrying the ipb-lux reporter may be useful as bioindicators of hydrocarbon pollution in the environment and may be particularly valuable for examining the bioavailability of inducing pollutants.
Consumer Willingness to Pay for Specialty Meats

As demand for organic and natural foods increases in the U.S., it is important to understand consumer preferences and willingness to pay in terms of premiums for specialty or non-traditional products. This information can assist specialty meat producers, such as organic, natural, and grass-fed producers in selecting sustainable pricing and production management practices, leading to long term profitability.
Targeting of acute myeloid leukaemia by cytokine‐induced killer cells redirected with a novel CD123‐specific chimeric antigen receptor

Current therapeutic regimens for acute myeloid leukaemia (AML) are still associated with high rates of relapse. Immunotherapy with T‐cells genetically modified to express chimeric antigen receptors (CARs) represents an innovative approach. Here we investigated the targeting of the interleukin three receptor alpha (IL3RA; CD123) molecule, which is overexpressed on AML bulk population, CD34+ leukaemia progenitors, and leukaemia stem cells (LSC) compared to normal haematopoietic stem/progenitor cells (HSPCs), and whose overexpression is associated with poor prognosis. Cytokine‐induced killer (CIK) cells were transduced with SFG‐retroviral‐vector encoding an anti‐CD123 CAR. Transduced cells were able to strongly kill CD123+ cell lines, as well as primary AML blasts. Interestingly, secondary colony experiments demonstrated that anti‐CD123.CAR preserved in vitro HSPCs, in contrast to a previously generated anti‐CD33.CAR, while keeping an identical cytotoxicity profile towards AML. Furthermore, limited killing of normal monocytes and CD123‐low‐expressing endothelial cells was noted, thus indicating a low toxicity profile of the anti‐CD123.CAR. Taken together, our results indicate that CD123‐specific CARs strongly enhance anti‐AML CIK functions, while sparing HSPCs and normal low‐expressing antigen cells, paving the way to develop novel immunotherapy approaches for AML treatment.
The Design and Execution of Performance Management Systems at State Level: A Comparative Analysis of Italy and Malaysia

ABSTRACT This comparative study analyses the experience of Italy and Malaysia in the design and execution of performance management systems at the state level. The article investigates how performance management systems have changed over the past decades, the motivations behind their metamorphoses, their common elements across the two countries, and what accounts for the respective progress. It also investigates the role that the institutional framework plays in making performance management systems robust. The study presents policy recommendations on how governments can create more robust performance management systems for enhanced accountability and transparency in an age of resource constraint.
Employment Challenges in Ethiopia

Unemployment (mainly as an urban phenomenon) and underemployment continue to be serious social problems in Ethiopia despite some improvements in recent years. This paper attempts to assess the labor market institutions, evaluate the existing labor market policies and discuss their role in explaining and solving the unemployment problem based on review of policy documents and relevant empirical literature. The study finds out that there are different policies and strategies introduced and implemented by the government for employment generations. Those policies and strategies on the demand side of the labor market include the special incentives and supports provided to private sectors and the public employment generation schemes. On the supply side of the labor market, there are significant efforts to improve labor productivity in both farm and off-farm activities. The potential of these interventions to have significant impact on employment has been constrained by the extensive informal sector in Ethiopia, the low demand for labor and lack of government budget. The Labor market institutions that govern employment relations in Ethiopia are generally found to be weak. This weakness is characterized by limitation of legal framework and lack of social dialogue among institutions.
Repricing and Executive Turnover

We examine whether the threat of executive turnover faced by a firm affects its decision to reprice stock options held by its executives. We estimate a model of voluntary turnover among top executives and show that the predicted turnover from this model is positively related to the probability of repricing. The relationship is robust to the inclusion of several known determinants of repricing. Our results are consistent with a model in which a tight labor market makes executives hard to replace, forcing firms to reprice stock options when they go underwater.
Does Work During Childhood Affect Adult’s Health? An Analysis for Guatemala

The diversity of potential relationships between child labor and health makes the empirical disentanglement of the causal relationship a difficult exercise. This paper examines the long run impact of child labour on health by controlling for unobserved household specific characteristics. In order to control for the unobserved households specific effect, we estimate a conditional fixed effect model using data on siblings constructed from the Guatemalan National Survey of Living Condition. The estimation results reinforce the conventional wisdom that child labor is harmful for health in the long run. The results can be interpreted as a lower bound of the true impact since healthier children are most likely to offer themselves for employment and to be appointed.
Comparison of Radial and Tangential Geometries for Cylindrical Panorama

This paper presents a new approach which builds 360-degree cylindrical panoramic images from multiple cameras. In order to ensure a perceptually correct result, mosaicing typically requires either a planar or near-planar scene, parallax-free camera motion between source frames, or a dense sampling of the scene. When these conditions are not satisfied, various artifacts may appear. There are many algorithms to overcome these problems. We propose a panoramic setup where cameras are placed evenly around a circle. Instead of looking outward, which is the traditional configuration, we propose to make the optical axes tangent to the camera circle, a "tangential" configuration. We will demonstrate that this configuration is very insensitive to depth estimation, which reduces stitching artifacts. This property is only limited by the fact that tangential cameras usually occlude each other along the circle. Beside an analysis and comparison of radial and tangential geometries, we provide an experimental setup with real panoramas obtained in realistic conditions.
Visual-olfactory immersive environment for product evaluation

Today smells are used for communicating information about products as household cleaners and food. However, smells can be also applied to any kind of products. Several researches have focused on integrating smells in virtual environments. The research questions addressed in this work concern whether Virtual Prototypes, including the sense of smell, can be used for evaluating products as effectively as studies performed in real environments, and whether smells can increase the users' sense of presence in the virtual environment. For this purpose, an experimental framework including a wearable olfactory display has been developed, and experimental tests have been performed.
The Arabidopsis ZINC FINGER PROTEIN3 Interferes with Abscisic Acid and Light Signaling in Seed Germination and Plant Development1[C][W][OPEN]

An Arabidopsis zinc finger protein acts as a negative regulator of ABA-suppressed seed germination and modulates plant development, fertility, and hypocotyl elongation under red light. Seed germination is controlled by environmental signals, including light and endogenous phytohormones. Abscisic acid (ABA) inhibits, whereas gibberellin promotes, germination and early seedling development, respectively. Here, we report that ZFP3, a nuclear C2H2 zinc finger protein, acts as a negative regulator of ABA suppression of seed germination in Arabidopsis (Arabidopsis thaliana). Accordingly, regulated overexpression of ZFP3 and the closely related ZFP1, ZFP4, ZFP6, and ZFP7 zinc finger factors confers ABA insensitivity to seed germination, while the zfp3 zfp4 double mutant displays enhanced ABA susceptibility. Reduced expression of several ABA-induced genes, such as RESPONSIVE TO ABSCISIC ACID18 and transcription factor ABSCISIC ACID-INSENSITIVE4 (ABI4), in ZFP3 overexpression seedlings suggests that ZFP3 negatively regulates ABA signaling. Analysis of ZFP3 overexpression plants revealed multiple phenotypic alterations, such as semidwarf growth habit, defects in fertility, and enhanced sensitivity of hypocotyl elongation to red but not to far-red or blue light. Analysis of genetic interactions with phytochrome and abi mutants indicates that ZFP3 enhances red light signaling by photoreceptors other than phytochrome A and additively increases ABA insensitivity conferred by the abi2, abi4, and abi5 mutations. These data support the conclusion that ZFP3 and the related ZFP subfamily of zinc finger factors regulate light and ABA responses during germination and early seedling development.
Inhibition of Porphyromonas gingivalis Biofilm by Oxantel

ABSTRACT Porphyromonas gingivalis is a major pathogen of chronic periodontitis and exists in a biofilm on the surface of the tooth root. Oxantel, a cholinergic anthelmintic and fumarate reductase inhibitor, significantly inhibited biofilm formation by P. gingivalis and disrupted established biofilms at concentrations below its MIC against planktonic cells. Oxantel was more effective against P. gingivalis in biofilm than metronidazole, a commonly used antibiotic for periodontitis.
Pollination Efficiency of Bumblebee Queens and Workers in the Alpine Shrub Rhododendron aureum

Rhododendron aureum is a weakly self-compatible alpine shrub pollinated by bumblebees. Flower visitation frequency and foraging behavior differed between queen bumblebees and workers. Queens exhibited less frequent flower visits, longer flight distances between inflorescences, and a smaller number of sequential inflorescence visits within patches than did worker bees. Flowering in early-snowmelt populations occurred in June, when only overwintered queens were available, while flowering in late-snowmelt populations occurred from late July to August, when frequent visits by workers were common. The fruit to flower ratio per inflorescence was lower in early-snowmelt populations due to quantitative pollen limitation, while the seed to ovule ratio per fruit was lower in late-snowmelt populations. This is because geitonogamous pollination by workers was common later in the season, which resulted in a high abortion rate of self-pollinated seeds, that is, qualitative pollen limitation. Thus, pollination efficiency, or the type of pollen limitation, shifts during the flowering season, reflecting the seasonal life cycle of bumblebees in the ecosystem. Many of the self-fertilized seeds aborted due to high inbreeding depression, and the outcrossing rate was ∼80% regardless of season.
Genetic risk for primary open-angle glaucoma determined by LMX1B haplotypes.

PURPOSE Primary open-angle glaucoma (POAG) is a common disease requiring early diagnosis and treatment to avoid asymptomatic visual field loss and eventual blindness. LMX1B mutations cause dominantly-inherited Nail-Patella syndrome in which approximately 33% of patients develop glaucoma. This study investigated the wider role of LMX1B in POAG. METHODS The contribution of variation at the LMXIB locus to risk of glaucoma was investigated in a case-control genetic association study in 272 patients with high-tension glaucoma (HTG), 37 patients with normal-tension glaucoma (NTG), 58 patients with ocular hypertension (OHT), and 276 controls. RESULTS Significant SNP associations were found for each patient group: rs7859156 was associated with HTG (P=0.0015; odds ratio [OR], 0.64) and OHT (P=0.0482; OR, 0.59); rs7854658 was associated with NTG (P=0.0041; OR, 0.30). A protective ATG haplotype (including rs7859156) was less prevalent in patients with raised intraocular pressure (22.7% in combined HTG+OHT group vs. 31.7% in controls; P=0.0005), and in patients with glaucoma (22.9% in combined HTG+NTG group vs. 31.7% in controls; P=0.0008). ATG carriers in these combined groups had a decreased risk of developing glaucoma (OR, 0.72 and OR, 0.73, respectively). A GCAGAC haplotype (including rs7854658) was also less prevalent in glaucoma patients (16.5% vs. 24.7%; P=0.0005) and carriers had a decreased risk of developing glaucoma (OR, 0.70). CONCLUSIONS LMX1B haplotypes influence susceptibility to glaucoma in the general population, suggesting altered LMX1B function predisposes to glaucomatous damage and that this role may be independent of raised intraocular pressure.
Social disclosure, legitimacy theory and the role of the state

Purpose - The principal objective of this paper is to expand the scope of legitimacy theory (LT) through a detailed analysis of the links that exist between the legitimising strategies of firms and the characteristics of the political environment in which they are developed. Designs/methodology/approach - A discourse analysis was performed on the social and environmental disclosure (SED) of a multinational in the automotive sector with an established presence in Spain, in the context of the relational dynamics between the firm/society/state. Different channels of information were compared to capture both the official discourse as represented in the annual reports of the multinational and the discourse of employees and the State as represented in the media. Findings - The results of the research show that the firm under study used SED strategically to legitimise a new production process through the manipulation of social perceptions, and that this strategy was supported implicitly and explicitly through ideological alignment with the State. Research limitations/implications - Despite a widely-held assumption of a pluralist political context, the State is presented here as aligning itself with corporate management as opposed to the welfare concerns of employees. Thus, future research calling for regulation of SED should preface such calls with consideration of the orientation of the State. Originality/value - In contrast with the dominant approach to LT that considers the relationship of the firm with its stakeholders, the present study widens the scope of LT to consider the interplay between firm legitimating strategies and state support for such strategies.