Miracle-dz/UniFAR-FTUs huggingface dataset:
Proteomic Analysis Reveals a Predominant NFE2L2 (NRF2) Signature in Canonical Pathway and Upstream Regulator Analysis of Leishmania-Infected Macrophages

CBA mice macrophages (MØ) control infection by Leishmania major and are susceptive to Leishmania amazonensis, suggesting that both parasite species induce distinct responses that play important roles in infection outcome. To evaluate the MØ responses to infection arising from these two Leishmania species, a proteomic study using a Multidimensional Protein Identification Technology (MudPIT) approach with liquid chromatography tandem mass spectrometry (LC-MS/MS) was carried out on CBA mice bone-marrow MØ (BMMØ). Following SEQUEST analysis, which revealed 2,838 proteins detected in BMMØ, data mining approach found six proteins significantly associated with the tested conditions. To investigate their biological significance, enrichment analysis was performed using Ingenuity Pathway Analysis (IPA). A three steps IPA approach revealed 4 Canonical Pathways (CP) and 7 Upstream Transcriptional Factors (UTFs) strongly associated with the infection process. NRF2 signatures were present in both CPs and UTFs pathways. Proteins involved in iron metabolism, such as heme oxigenase 1 (HO-1) and ferritin besides sequestosome (SQSMT1 or p62) were found in the NRF2 CPs and the NRF2 UTFs. Differences in the involvement of iron metabolism pathway in Leishmania infection was revealed by the presence of HO-1 and ferritin. Noteworty, HO-1 was strongly associated with L. amazonensis infection, while ferritin was regulated by both species. As expected, higher HO-1 and p62 expressions were validated in L. amazonensis-infected BMMØ, in addition to decreased expression of ferritin and nitric oxide production. Moreover, BMMØ incubated with L. amazonensis LPG also expressed higher levels of HO-1 in comparison to those stimulated with L. major LPG. In addition, L. amazonensis-induced uptake of holoTf was higher than that induced by L. major in BMMØ, and holoTf was also detected at higher levels in vacuoles induced by L. amazonensis. Taken together, these findings indicate that NRF2 pathway activation and increased HO-1 production, together with higher levels of holoTf uptake, may promote permissiveness to L. amazonensis infection. In this context, differences in protein signatures triggered in the host by L. amazonensis and L. major infection could drive the outcomes in distinct clinical forms of leishmaniasis.
The Social Impact of Musical Engagement for Young Adults With Learning Difficulties: A Qualitative Study

There is evidence that music interventions can offer opportunities for creative, psychological, and social developments for individuals with mild to profound learning disabilities, addressing the disadvantages they face in respect of social outcomes. This paper reports on a qualitative study investigating a community music intervention for such a population. Thirty-seven adult service users (12 female, 25 male) took part in weekly music workshops for 10 weeks. Their learning difficulties ranged from mild to profound, and their levels of independence ranged from requiring constant one-to-one care to living alone in sheltered accommodation. Interviews were conducted at multiple time points with music and resource center staff as well as participants and members of their families and other center users; researchers also observed all workshops, taking field notes. Thematic analysis of the data informed understanding of the disadvantages facing participants, their experience of the workshop program and its immediate and wider social outcomes, as well as suggesting key mechanisms for effects. Disadvantages and barriers facing participants included: limited access to enjoying or learning music; boredom, isolation, and limited networks; lack of experience of new social contexts; and an associated lack of confidence, low mood or self-esteem. Participants were found to enjoy and sustain engagement with a program of dedicated group music workshops delivered by staff trained in an empathic and inclusive approach. Impacts included an ongoing enthusiasm to engage in music; wider recognition of musicality; increased self-confidence; being happier, more relaxed, and/or enthusiastic after the workshops; better ability to interact with unfamiliar situations and people; and participation in social activities for an unprecedented length of time. Key factors in achieving those impacts are that participants: had fun and interacted socially; felt secure, welcomed, and involved at all times; exercised choice; worked with others in nonverbal tasks; and encountered challenge while engaging and progressing at their own rate.
Maternal Immune Activation and Related Factors in the Risk of Offspring Psychiatric Disorders

Maternal immune activation (MIA) at the time of gestation has been linked to increased risk of neurodevelopmental psychiatric disorders. Animal and human models have been used to evaluate the relationship between MIA and these outcomes. Given that each of these two disciplines of study have their benefits and limitations, a translational perspective is expected to illuminate more than by the use of any single approach. In this article, we discuss this translational framework and explore how it may be enhanced by the utilization of epigenetic studies and by investigating the microbiome. In this perspectives piece, we focus on the impact of epidemiologic studies, animal models, and preclinical studies in the literature on MIA as well as the potential for greater integration between fields.
Iron-Dependent Trafficking of 5-Lipoxygenase and Impact on Human Macrophage Activation

5-lipoxygenase (5-LOX) is a non-heme iron-containing dioxygenase expressed in immune cells that catalyzes the two initial steps in the biosynthesis of leukotrienes. It is well known that 5-LOX activation in innate immunity cells is related to different iron-associated pro-inflammatory disorders, including cancer, neurodegenerative diseases, and atherosclerosis. However, the molecular and cellular mechanism(s) underlying the interplay between iron and 5-LOX activation are largely unexplored. In this study, we investigated whether iron (in the form of Fe3+ and hemin) might modulate 5-LOX influencing its membrane binding, subcellular distribution, and functional activity. We proved by fluorescence resonance energy transfer approach that metal removal from the recombinant human 5-LOX, not only altered the catalytic activity of the enzyme, but also impaired its membrane-binding. To ascertain whether iron can modulate the subcellular distribution of 5-LOX in immune cells, we exposed THP-1 macrophages and human primary macrophages to exogenous iron. Cells exposed to increasing amounts of Fe3+ showed a redistribution (ranging from ~45 to 75%) of the cytosolic 5-LOX to the nuclear fraction. Accordingly, confocal microscopy revealed that acute exposure to extracellular Fe3+, as well as hemin, caused an overt increase in the nuclear fluorescence of 5-LOX, accompanied by a co-localization with the 5-LOX activating protein (FLAP) both in THP-1 macrophages and human macrophages. The functional relevance of iron overloading was demonstrated by a marked induction of the expression of interleukin-6 in iron-treated macrophages. Importantly, pre-treatment of cells with the iron-chelating agent deferoxamine completely abolished the hemin-dependent translocation of 5-LOX to the nuclear fraction, and significantly reverted its effect on interleukin-6 overexpression. These results suggest that exogenous iron modulates the biological activity of 5-LOX in macrophages by increasing its ability to bind to nuclear membranes, further supporting a role for iron in inflammation-based diseases where its homeostasis is altered and suggesting further evidence of risks related to iron overload.
Genetic algorithms, their applications and models in nonlinear systems identification

The Genetic Algorithm was used to estimate the hydraulic compliance of the hydraulic system on the UBC teleoperated heavy duty excavator. Using real recorded and simulation data from the excavator, the Genetic Algorithm has successfully identified the compliance of single link and multilink hydraulic system of the excavator. A Parallel GA ( PGA ) was implemented with 16 T800 Transputers. It achieved a speedup factor of 12 over a traditional GA. With such a high speedup factor, real-time monitoring of hydraulic compliance and other hydraulic parameters is becoming possible. New mechanisms such as the distributed fitness function, the active error analysis were used to enhance the performance of a PGA. A PGA which incorporated these mechanisms actually outperformed a traditional GA in key areas such as variance of the estimated parameter and parameter tracking ability. Finally, a physical model that explains the fundamental properties of GAs was introduced. The physical model ( a hypercube ) not only provides an excellent explanation of GAs searching power, but also gives insight to GAs users ways to improve and to predict the performance of GAs in most applications.
MICROPEROXIDASE

INTRODUCTION This communication is a report on some physical and chemical properties of MP and on a striking difference between the distribution of MP and that of HRP when the two substances are administered to mice . In particular, MP penetrates into an extracellular compartment from which HRP is largely excluded . This finding is consistent with the smaller molecular size of MP and suggests that MP may be generally useful for demonstrating the existence of channels not revealed in the living state by other tracers . Ultrastructural tracers serve the important purpose of defining tissue or cellular compartments and their interconnecting channels . The ideal tracer substance should be (a) nontoxic and physiologically inert, (b) composed of uniform particles of known size, (c) immobilized in its in vivo position by fixation, (d) capable of being accurately localized when viewed with the electron microscope, and (e) demonstrable at low concentration . In addition, small molecular size is essential for many applications . For example, channels as narrow as 20 A have been demonstrated with colloidal lanthanum (12), a tracer smaller than almost all others now in use . Because of its toxicity, however, colloidal lanthanum must generally be applied to fixed rather than living tissue specimens. This complicates the interpretation of observations made with this tracer, since the effects of fixation on pore size or channel width are almost unknown . Several nontoxic tracers are available for electron microscopy, but they are larger than 20 A in diameter : for example, ferritin (diameter 100120 A, mol wt 900,000), horseradish peroxidase (HRP, diameter 50-60 A, mol wt 40,000), and cytochrome c (diameter around 30 A, mol wt 12,000). (For discussions of these and other tracers, see references 10, 11, 16, 17, and 20 .) Clearly there is a need for an ultrastructural tracer that is small, nontoxic, capable of being accurately localized, and demonstrable at low concentration . I have proposed as a tracer a hemepeptide (Fig . 1) with a molecular weight of only 1900 (9) . This tracer, which was given the name microperoxidase (MP), does not appear to be toxic at the concentrations used in tracer studies . Like HRP and cytochrome c, MP is demonstrated for the electron microscope through its peroxidatic activity, which on a weight basis is about 1 /4 that of HRP and 150 times that of cytochrome c . MP is readily demonstrated at low concentration, and the localization is as good as that obtained with HRP.
Cftr

The goal of the experiments described here was to explore the possible role of fixed charges in determining the conduction properties of CFTR. We focused on transmembrane segment 6 (TM6) which contains four basic residues (R334, K335, R347, and R352) that would be predicted, on the basis of their positions in the primary structure, to span TM6 from near the extracellular (R334, K335) to near the intracellular (R347, R352) end. Cysteines substituted at positions 334 and 335 were readily accessible to thiol reagents, whereas those at positions 347 and 352 were either not accessible or lacked significant functional consequences when modified. The charge at positions 334 and 335 was an important determinant of CFTR channel function. Charge changes at position 334—brought about by covalent modification of engineered cysteine residues, pH titration of cysteine and histidine residues, and amino acid substitution—produced similar effects on macroscopic conductance and the shape of the I-V plot. The effect of charge changes at position 334 on conduction properties could be described by electrodiffusion or rate-theory models in which the charge on this residue lies in an external vestibule of the pore where it functions to increase the concentration of Cl adjacent to the rate-limiting portion of the conduction path. Covalent modification of R334C CFTR increased single-channel conductance determined in detached patches, but did not alter open probability. The results are consistent with the hypothesis that in wild-type CFTR, R334 occupies a position where its charge can influence the distribution of anions near the mouth of the pore.
Exploratory Case Study on Sustainability Analysis with a Startup for Business Models

Start-up businesses are often not primarily concerned with the overall sustainability impact of their business idea. However, designing sustainability into the start-up business idea from the start may improve their long-term impacts and success but requires additional knowledge and time. In this paper, we perform a case study of the start-up Partneur, who are developing an online platform for developing business ideas according to the Business Model Canvas. We show the usage of our artifact-based analysis approach and discuss observations and lessons learned. The approach provided new insights to Partneur, and might, in turn, inform their future users on how to incorporate sustainability into their business idea as well.
A hidden Markov model for matching spatial networks

: Datasets of the same geographic space at different scales and temporalities are increasingly abundant, paving the way for new scientiﬁc research. These datasets require data integration, which implies linking homologous entities in a process called data matching that remains a challenging task, despite a quite substantial literature, because of data imperfections and heterogeneities. In this paper, we present an approach for matching spatial networks based on a hidden Markov model (HMM) that takes full beneﬁt of the underlying topology of networks. The approach is assessed using four heterogeneous datasets (streets, roads, railway, and hydrographic networks), showing that the HMM algorithm is robust in regards to data heterogeneities and imperfections (geometric discrepancies and differences in level of details) and adaptable to match any type of spatial networks. It also has the advantage of requiring no mandatory parameters, as proven by a sensitivity exploration, except a distance threshold that ﬁlters potential matching candidates in order to speed-up the process. Finally, a comparison with a commonly cited approach highlights good matching accuracy and completeness.
Gaming at Work to Save Energy - Learnings from Workers Playing a Cooperative Game

Workplaces constitute a substantial part of the world’s energy consumption. In this paper we study how a cooperative game, EnerSpace, could be used to increase energy awareness and support energy conservation. In the study, after a one-week baseline period, 8 workers played EnerSpace for one week. They competed in two teams that each powered a spaceship with their energy saving on a resource exploitation trip to Mars. Each worker also had an avatar in the spaceship that reported personal consumption data using face recognition. The participant efforts and abilities to conserve energy affected the speed of the spaceship and the living condition of their avatars. The results show that workers decreased their overall energy consumption, especially on the weekend. Based on our results we discuss 1) designing for energy conservation when absent from the workplace, 2) how using the coffee room created energy conservation narratives but hampered local experimentation and learning, 3) team formation to support energy conservation and team spirit, and 4) challenges concerning games centered on baseline comparison for energy conservation. Author
The phylogenetic approach for viral infectious disease evolution and epidemiology: An updating review

In the last decade, the phylogenetic approach is recurrent in molecular evolutionary analysis. On 12 May, 2019, about 2 296 213 papers are found, but typing “phylogeny” or “epidemiology AND phylogeny” only 199 804 and 20 133 are retrieved, respectively. Molecular epidemiology in infectious diseases is widely used to define the source of infection as so as the ancestral relationships of individuals sampled from a population. Coalescent theory and phylogeographic analysis have had scientific application in several, recent pandemic events, and nosocomial outbreaks. Hepatitis viruses and immunodeficiency virus (human immunodeficiency virus) have been largely studied. Phylogenetic analysis has been recently applied on Polyomaviruses so as in the more recent outbreaks due to different arboviruses type as Zika and chikungunya viruses discovering the source of infection and the geographic spread. Data on sequences isolated by the microorganism are essential to apply the phylogenetic tools and research in the field of infectious disease phylodinamics is growing up. There is the need to apply molecular phylogenetic and evolutionary methods in areas out of infectious diseases, as translational genomics and personalized medicine. Lastly, the application of these tools in vaccine strategy so as in antibiotic and antiviral researchers are encouraged.
T Regulatory CD4+CD25+FoxP3+ Lymphocytes in the Peripheral Blood of Left-Sided Colorectal Cancer Patients

Background and objectives: T regulatory lymphocytes (Treg) are one of the subsets of T-lymphocytes involved in the interaction of neoplastic tumors and the host immune system, and they may impair the immune reaction against cancer. It has been shown that Treg are increased in the peripheral blood of patients with various cancers. In colorectal cancer, the prognostic role of Treg remains controversial. Colorectal cancer is a heterogenous disease, with many variations stemming from its primary tumor location. The aim of this study is to analyse the relationship between the amount of Treg in the peripheral blood of patients with left-sided colorectal cancer in various stages of disease and long-term survival. Materials and Methods: A prospective analysis of 94 patients with left-sided colorectal cancer and a group of 21 healthy volunteers was carried out. Treg levels in peripheral blood were analysed using flow cytometry. Results: There was a statistically significant difference between the amount of Treg in the Ist and IInd TNM stages (p = 0.047). The number of Treg in the entire study group was significantly lower than in the control group (p = 0.008) and between patients in stages II and III and the control group (p = 0.003 and p = 0.018). The group of pT3+pT4 patients also had significantly lower Treg counts in their peripheral blood than the control group (p = 0.005). In the entire study group, the level of Treg cells in the peripheral blood had no influence on survival. The analysis of the TNM stage subgroups also showed no difference in survival between patients with “low” and “high” Treg counts. Conclusion: The absolute number of Treg in the peripheral blood of patients with left-sided colorectal cancer was significantly decreased in comparison to healthy controls, especially for patients with stage II+III disease. Treg presence in the peripheral blood had no impact on survival.
Lower Back Injuries in National Collegiate Athletic Association Football Players: A 5-Season Epidemiological Study

Background: Low back injuries are common in collegiate football players and can frequently lead to persistent pain, reinjuries, and time lost from participation. Purpose: To describe the epidemiology of back injuries in National Collegiate Athletic Association (NCAA) football players during the 2009/2010 through 2013/2014 academic years utilizing the NCAA Injury Surveillance Program (ISP) database. Study Design: Descriptive epidemiology study. Methods: A convenience sample of NCAA varsity football teams was utilized to determine the rates and patterns of back injuries as well as to generate national injury estimates. The rates and distribution of back injuries were identified within the context of mechanism of injury, injury chronicity, and time lost from sport. Injury rates were calculated as the number of injuries divided by the total number of athlete-exposures (AEs). Incidence rate ratios were calculated to compare the rates of injury between season, event type, mechanism of injury, injury chronicity, and time lost from sport. Results: Nationally, there were 267 low back injuries reported in the database. These were used to estimate 7076 back injuries over the 5-year period, approximately 82% of which were new injuries. The injuries occurred at a rate of 2.70 per 10,000 AEs. Overall, injuries were 3.12 times more likely to occur in competitions than in practices. Athletes were 4.67 times more likely to sustain a back injury during the preseason compared with the postseason but were 1.41 times more likely to sustain a low back injury during the preseason compared with the regular season. Both contact and noncontact were reported equally as the mechanism of injury (37.8% and 38.3%, respectively), and unspecified low back pain was the most common injury (64.2%). Only 1.6% of patients required surgery for their injury, and the majority of athletes (59.6%) returned to play within 24 hours. Conclusion: There was a relatively high rate of lumbar back injuries at the collegiate level (2.70/10,000 AEs), the majority of which were new injuries. About 18% of reported injuries were reinjuries. Although very few required surgery, a careful examination and work-up should be conducted to evaluate each injury. Regimented physical therapy and reconditioning programs are recommended to avert reinjuries.
Prevalence of Burnout among Primary Health Care Staff and Its Predictors: A Study in Iran

Burnout, which is an emerging challenge in health systems, is very common among primary health care (PHC) workers. The aim of this study was to investigate the level of burnout among PHC workers, and its predictive factors, in a region in the west of Iran. In this cross-sectional study, all the health network staff (n = 539) were enrolled. The data collection instrument was the Maslach Burnout Inventory (MBI), which consists of 22 items and the three subscales of emotional exhaustion (EE), depersonalization (DP), and personal achievement (PA). High scores in EE and DP and low scores in PA are indicative of high burnout. Logistic regression was used to determine the predictors of high burnout. The data were analyzed using SPSS version 16. The findings showed that 90.5% of the staff had high DP, 55.3% had high EE, and 98.9% had low PA scores. Also, 52.9% (277 people) of the staff suffered from high burnout. Single people (OR = 3.33), less experienced employees (OR = 9.09), people aged over 35 years (OR = 2.35), physicians (OR = 1.72), and staff with permanent employment (OR = 5.0) were more likely to suffer high levels of burnout. We conclude that burnout is a common problem in PHC workers. Less experienced, younger, single employees and physicians were more at risk of suffering from high burnout. Preventive measures, such as strengthening social skills, communication competencies, and coping strategies, and reduction of risk factors such as job stress, are suggested for reducing employees’ risk of burnout.