Curcuma longa-Based Optical Sensor for Hydrochloric Acid and Ammonia Vapor Detection.

In this research, we present a prototype optical system that offers significant advances in detecting hydrochloric acid (HCl) and ammonia (NH3) vapors. The system utilizes a natural pigment sensor based on Curcuma longa that is securely attached to a glass surface support. Through extensive development and testing with HCl (37% aqueous solution) and NH3 (29% aqueous solution) solutions, we have successfully demonstrated the effectiveness of our sensor. To facilitate the detection process, we have developed an injection system that exposes C. longa pigment films to the targeted vapors. The interaction between the vapors and the pigment films triggers a distinct color change, which is then analyzed by the detection system. By capturing the transmission spectra of the pigment film, our system allows a precise comparison of these spectra at different concentrations of the vapors. Our proposed sensor exhibits remarkable sensitivity, allowing the detection of HCl at a concentration of 0.009 ppm using only 100 µL (2.3 mg) of pigment film. In addition, it can detect NH3 at a concentration of 0.03 ppm with a 400 µL (9.2 mg) pigment film. Integrating C. longa as a natural pigment sensor in an optical system opens up new possibilities for detecting hazardous gases. The simplicity and efficiency of our system, combined with its sensitivity, make it an attractive tool in environmental monitoring and industrial safety applications.

A Tailored Approach to Leishmaniases Vaccination: Comparative Evaluation of the Efficacy and Cross-Protection Capacity of DNA vs. Peptide-Based Vaccines in a Murine Model.

Zoonotic leishmaniases are a worldwide public health problem for which the development of effective vaccines remains a challenge. A vaccine against leishmaniases must be safe and affordable and should induce cross-protection against the different disease-causing species. In this context, the DNA vaccine pHisAK70 has been demonstrated to induce, in a murine model, a resistant phenotype against L. major, L. infantum, and L. amazonensis. Moreover, a chimeric multiepitope peptide, HisDTC, has been obtained by in silico analysis from the histone proteins encoded in the DNA vaccine and has showed its ability to activate a potent CD4+ and CD8+ T-cell protective immune response in mice against L. infantum infection. In the present study, we evaluated the plasmid DNA vaccine pHisAK70 in comparison with the peptide HisDTC (with and without saponin) against L. major and L. infantum infection. Our preliminary results showed that both formulations were able to induce a potent cellular response leading to a decrease in parasite load against L. infantum. In addition, the DNA candidate was able to induce better lesion control in mice against L. major. These preliminary results indicate that both strategies are potentially effective candidates for leishmaniases control. Furthermore, it is important to carry out such comparative studies to elucidate which vaccine candidates are the most appropriate for further development.

Transcriptomic Profile of Canine DH82 Macrophages Infected by Leishmania infantum Promastigotes with Different Virulence Behavior.

Zoonotic visceral leishmaniosis caused by Leishmania infantum is an endemic disease in the Mediterranean Basin affecting mainly humans and dogs, the main reservoir. The leishmaniosis outbreak declared in the Community of Madrid (Spain) led to a significant increase in human disease incidence without enhancing canine leishmaniosis prevalence, suggesting a better adaptation of the outbreak's isolates by other host species. One of the isolates obtained in the focus, IPER/ES/2012/BOS1FL1 (BOS1FL1), has previously demonstrated a different phenotype than the reference strain MCAN/ES/1996/BCN150 (BCN150), characterized by a lower infectivity when interacting with canine macrophages. Nevertheless, not enough changes in the cell defensive response were found to support their different behavior. Thus, we decided to investigate the molecular mechanisms involved in the interaction of both parasites with DH82 canine macrophages by studying their transcriptomic profiles developed after infection using RNA sequencing. The results showed a common regulation induced by both parasites in the phosphoinositide-3-kinase-protein kinase B/Akt and NOD-like receptor signaling pathways. However, other pathways, such as phagocytosis and signal transduction, including tumor necrosis factor, mitogen-activated kinases and nuclear factor-κB, were only regulated after infection with BOS1FL1. These differences could contribute to the reduced infection ability of the outbreak isolates in canine cells. Our results open a new avenue to investigate the true role of adaptation of L. infantum isolates in their interaction with their different hosts.

Validity, Reliability, and Sensitivity to Exercise-Induced Fatigue of a Customer-Friendly Device for the Measurement of the Brain's Direct Current Potential.

ABSTRACT: Valenzuela, PL, Sánchez-Martínez, G, Torrontegi, E, Vázquez-Carrión, J, Montalvo, Z, and Kara, O. Validity, reliability, and sensitivity to exercise-induced fatigue of a customer-friendly device for the measurement of the brain's direct current potential. J Strength Cond Res 36(6): 1605-1609, 2022-This study aimed to determine the validity, reliability, and sensitivity to exercise-induced fatigue of the brain's direct current (DC) potential measured with a commercially available and customer-friendly electroencephalography (EEG) device and Omegawave (OW). The study was composed of 3 different experiments as follows: (a) we compared the DC potential values obtained simultaneously in 31 subjects with both OW and a research-quality EEG system; (b) 3 consecutive DC potential measurements with OW were taken at rest on the same day in 25 subjects for reliability analyses; and (c) sensitivity to fatigue was assessed in 9 elite badminton players through the measurement of the DC potential with OW-as well as other fatigue-related measures (e.g., Hooper's index, heart rate variability, jump ability, and simple and complex reaction times)-24 hours after both a day of rest and of strenuous exercise, which were performed in a crossover and randomized design. The DC potential measured with OW was reliable (intraclass correlation coefficient = 0.97) and significantly correlated to that of EEG (r = 0.55, p = 0.001), although significant differences were observed between systems (p < 0.001). Compared with the rest day, strenuous exercise resulted in an impaired Hooper's index (p = 0.010) and jump ability (p = 0.008), longer simple (p = 0.038) and complex reaction times (p = 0.011), and a trend toward sympathetic dominance (standard deviation of normal to normal R-R intervals, p = 0.042; root mean square of differences between consecutive R-R intervals, p = 0.068). In turn, no significant differences were found between sessions for the DC potential (p = 0.173). In summary, the DC potential measured with OW was reliable and modestly correlated to that measured with EEG, but no differences were observed in response to the delayed fatigue (after 24 hours) elicited by strenuous exercise in elite athletes.

Reference power values for the jump squat exercise in elite athletes: A multicenter study.

The present study aimed to provide reference values for lower-limb muscle power assessed during the incremental jump squat (JS) test in elite athletes (i.e., professional athletes competing at international level). We pooled data from all JS tests performed by elite athletes of different sports in two high-performance centres between 2015 and 2019, and computed reference values (i.e., terciles) for mean power (MP), mean propulsive power (MPP), and peak power (PP). Reference values were obtained from 684 elite athletes (458 male and 226 female) of 16 different sports (boxing, judo, karate, fencing, taekwondo, wrestling, basketball, soccer, futsal, handball, rugby union, badminton, tennis, long distance running, triathlon, and sprinting). Significant differences (p < 0.001) were found between male and female athletes for MP (7.47 ± 1.93 and 6.15 ± 1.68 W·Kg-1, respectively), MPP (10.50 ± 2.75 and 8.63 ± 2.43 W·Kg-1), and PP (23.64 ± 6.12 and 19.35 ± 5.49 W·Kg-1). However, the velocity at which these power measures was attained seemed to be independent of sex (~0.95, 1.00 and 2.00 m·s-1 for mean, mean propulsive, and peak velocity, respectively) and homogeneous across different sport disciplines (coefficient of variation <10%). These data can be used to classify athletes' power capabilities, and the optimum velocity ranges provided here could be useful for training purposes.

The receptor Slamf1 on the surface of myeloid lineage cells controls susceptibility to infection by Trypanosoma cruzi.

Trypanosoma cruzi, the protozoan parasite responsible for Chagas' disease, causes severe myocarditis often resulting in death. Here, we report that Slamf1-/- mice, which lack the hematopoietic cell surface receptor Slamf1, are completely protected from an acute lethal parasite challenge. Cardiac damage was reduced in Slamf1-/- mice compared to wild type mice, infected with the same doses of parasites, as a result of a decrease of the number of parasites in the heart even the parasitemia was only marginally less. Both in vivo and in vitro experiments reveal that Slamf1-defIcient myeloid cells are impaired in their ability to replicate the parasite and show altered production of cytokines. Importantly, IFN-γ production in the heart of Slamf1 deficient mice was much lower than in the heart of wt mice even though the number of infiltrating dendritic cells, macrophages, CD4 and CD8 T lymphocytes were comparable. Administration of an anti-Slamf1 monoclonal antibody also reduced the number of parasites and IFN-γ in the heart. These observations not only explain the reduced susceptibility to in vivo infection by the parasite, but they also suggest human Slamf1 as a potential target for therapeutic target against T. cruzi infection.

Microbial Matryoshka: Addressing the Relationship between Pathogenic Flagellated Protozoans and Their RNA Viral Endosymbionts (Family Totiviridae).

Three genera of viruses of the family Totiviridae establish endosymbiotic associations with flagellated protozoa responsible for parasitic diseases of great impact in the context of One Health. Giardiavirus, Trichomonasvirus, and Leishmaniavirus infect the protozoa Giardia sp., Trichomonas vaginalis, and Leishmania sp., respectively. In the present work, we review the characteristics of the endosymbiotic relationships established, the advantages, and the consequences caused in mammalian hosts. Among the common characteristics of these double-stranded RNA viruses are that they do not integrate into the host genome, do not follow a lytic cycle, and do not cause cytopathic effects. However, in cases of endosymbiosis between Leishmaniavirus and Leishmania species from the Americas, and between Trichomonasvirus and Trichomonas vaginalis, it seems that it can alter their virulence (degree of pathogenicity). In a mammalian host, due to TLR3 activation of immune cells upon the recognition of viral RNA, uncontrolled inflammatory signaling responses are triggered, increasing pathological damage and the risk of failure of conventional standard treatment. Endosymbiosis with Giardiavirus can cause the loss of intestinal adherence of the protozoan, resulting in a benign disease. The current knowledge about viruses infecting flagellated protozoans is still fragmentary, and more research is required to unravel the intricacies of this three-way relationship. We need to develop early and effective diagnostic methods for further development in the field of translational medicine. Taking advantage of promising biotechnological advances, the aim is to develop ad hoc therapeutic strategies that focus not only on the disease-causing protozoan but also on the virus.

Solid Lipid Nanoparticles Enhancing the Leishmanicidal Activity of Delamanid.

Leishmaniasis, a zoonotic parasitic disease transmitted by infected sandflies, impacts nearly 1 million people yearly and is endemic in many countries across Asia, Africa, the Americas, and the Mediterranean; despite this, it remains a neglected disease with limited effective treatments, particularly in impoverished communities with limited access to healthcare. This study aims to repurpose approved drugs for an affordable leishmaniasis treatment. After the screening of potential drug candidates by reviewing databases and utilizing molecular docking analysis, delamanid was chosen to be incorporated into solid lipid nanoparticles (SLNPs). Both in cellulo and in vivo tests confirmed the successful payload release within macrophages and through the epidermis following topical application on murine skin. The evaluation of macrophages infected with L. infantum amastigotes showed that the encapsulated delamanid exhibited greater leishmanicidal activity compared with the free drug. The process of encapsulating delamanid in SLNPs, as demonstrated in this study, places a strong emphasis on employing minimal technology, ensuring energy efficiency, cost-effectiveness, and reproducibility. It enables consistent, low-cost production of nanomedicines, even on a small scale, offering a promising step toward more accessible and effective leishmaniasis treatments.

Neglected Zoonotic Diseases: Advances in the Development of Cell-Penetrating and Antimicrobial Peptides against Leishmaniosis and Chagas Disease.

In 2020, the WHO established the road map for neglected tropical diseases 2021-2030, which aims to control and eradicate 20 diseases, including leishmaniosis and Chagas disease. In addition, since 2015, the WHO has been developing a Global Action Plan on Antimicrobial Resistance. In this context, the achievement of innovative strategies as an alternative to replace conventional therapies is a first-order socio-sanitary priority, especially regarding endemic zoonoses in poor regions, such as those caused by Trypanosoma cruzi and Leishmania spp. infections. In this scenario, it is worth highlighting a group of natural peptide molecules (AMPs and CPPs) that are promising strategies for improving therapeutic efficacy against these neglected zoonoses, as they avoid the development of toxicity and resistance of conventional treatments. This review presents the novelties of these peptide molecules and their ability to cross a whole system of cell membranes as well as stimulate host immune defenses or even serve as vectors of molecules. The efforts of the biotechnological sector will make it possible to overcome the limitations of antimicrobial peptides through encapsulation and functionalization methods to obtain approval for these treatments to be used in clinical programs for the eradication of leishmaniosis and Chagas disease.

Mitigating an undesirable immune response of inherent susceptibility to cutaneous leishmaniosis in a mouse model: the role of the pathoantigenic HISA70 DNA vaccine.

Leishmania major is the major cause of cutaneous leishmaniosis (CL) outside of the Americas. In the present study we have cloned six Leishmania genes (H2A, H2B, H3, H4, A2 and HSP70) into the eukaryotic expression vector pCMVß-m2a, resulting in pCMV-HISA70m2A, which encodes all six pathoantigenic proteins as a single polyprotein. This expression plasmid has been evaluated as a novel vaccine candidate in the BALB/c mouse model of CL. The DNA vaccine shifted the immune response normally induced by L. major infection away from a Th2-specific pathway to one of basal susceptibility. Immunization with pCMV-HISA70m2A dramatically reduced footpad lesions and lymph node parasite burdens relative to infected control mice. Complete absence of visceral parasite burden was observed in all 12 immunized animals but not in any of the 24 control mice. Moreover, vaccinated mice produced large amounts of IFN-γ, IL-17 and NO at 7 weeks post-infection (pi), and they showed lower arginase activity at the site of infection, lower IL-4 production and a weaker humoral immune response than infected control mice. Taken together, these results demonstrate the ability of the HISA70 vaccine to shift the murine immune response to L. major infection away from an undesirable, Th2-specific pathway to a less susceptible-like pathway involving Th1 and Th17 cytokine profiles.

Subtilase cytotoxin-coding genes in verotoxin-producing Escherichia coli strains from sheep and goats differ from those from cattle.

Subtilase cytotoxin (SubAB) from verotoxin (VT)-producing Escherichia coli (VTEC) strains was first described in the 98NK2 strain and has been associated with human disease. However, SubAB has recently been found in two VT-negative E. coli strains (ED 591 and ED 32). SubAB is encoded by two closely linked, cotranscribed genes (subA and subB). In this study, we investigated the presence of subAB genes in 52 VTEC strains isolated from cattle and 209 strains from small ruminants, using PCR. Most (91.9%) VTEC strains from sheep and goats and 25% of the strains from healthy cattle possessed subAB genes. The presence of subAB in a high percentage of the VTEC strains from small ruminants might increase the pathogenicity of these strains for human beings. Some differences in the results of PCRs and in the association with some virulence genes suggested the existence of different variants of subAB. We therefore sequenced the subA gene in 12 strains and showed that the subA gene in most of the subAB-positive VTEC strains from cattle was almost identical (about 99%) to that in the 98NK2 strain, while the subA gene in most of the subAB-positive VTEC strains from small ruminants was almost identical to that in the ED 591 strain. We propose the terms subAB1 to describe the SubAB-coding genes resembling that in the 98NK2 strain and subAB2 to describe those resembling that in the ED 591 strain.

Mechanisms of resistance and susceptibility to experimental visceral leishmaniosis: BALB/c mouse versus Syrian hamster model.

Several animal models have been established to study visceral leishmaniosis (VL), a worldwide vector-borne disease affecting humans and domestic animals that constitutes a serious public health problem. BALB/c mice and Syrian hamsters are the most widely used experimental models. In this paper, we summarize the advantages and disadvantages of these two experimental models and discuss the results obtained using these models in different studies of VL. Studies using the BALB/c mouse model have underscored differences between the liver and spleen in the course of VL, indicating that pathological evaluation of the visceral organs is essential for understanding the immune mechanisms induced by Leishmania infantum infection. The main goal of this review is to collate the relevant literature on Leishmania pathogenesis into a sequence of events, providing a schematic view of the main components of adaptive and innate immunity in the liver and spleen after experimental infection with L. infantum or L. donovani. This review also presents several viewpoints and reflections about some controversial aspects of Leishmania research, including the choice of experimental model, route of administration, inoculum size and the relevance of pathology (intimately linked to parasite persistence): a thorough understanding of which is essential for future VL research and the successful development of efficient control strategies for Leishmania spp.

A Framework for Implementing Metaheuristic Algorithms Using Intercellular Communication.

Metaheuristics (MH) are Artificial Intelligence procedures that frequently rely on evolution. MH approximate difficult problem solutions, but are computationally costly as they explore large solution spaces. This work pursues to lay the foundations of general mappings for implementing MH using Synthetic Biology constructs in cell colonies. Two advantages of this approach are: harnessing large scale parallelism capability of cell colonies and, using existing cell processes to implement basic dynamics defined in computational versions. We propose a framework that maps MH elements to synthetic circuits in growing cell colonies to replicate MH behavior in cell colonies. Cell-cell communication mechanisms such as quorum sensing (QS), bacterial conjugation, and environmental signals map to evolution operators in MH techniques to adapt to growing colonies. As a proof-of-concept, we implemented the workflow associated to the framework: automated MH simulation generators for the gro simulator and two classes of algorithms (Simple Genetic Algorithms and Simulated Annealing) encoded as synthetic circuits. Implementation tests show that synthetic counterparts mimicking MH are automatically produced, but also that cell colony parallelism speeds up the execution in terms of generations. Furthermore, we show an example of how our framework is extended by implementing a different computational model: The Cellular Automaton.

Properties of virulence emergence of Leishmania infantum isolates from Phlebotomus perniciosus collected during the human leishmaniosis outbreak in Madrid, Spain. Hepatic histopathology and immunological parameters as virulence markers in the mouse model.

Recent anthropic activity related to the construction of the Bosquesur Green Park in a large urban setting in Madrid (Spain) has resulted in the largest reported community outbreak of human leishmaniosis in Europe. Previous phylogenetic and molecular-typing studies of parasite isolates have implicated the Leishmania infantum ITS-Lombardi genotype in this outbreak. In an unusual scenario, visceral leishmaniosis (VL) is affecting a significant number of individuals, suggesting that an increase in parasite virulence has occurred. In this work, using an in vivo BALB/c model of VL, we aimed to investigate the properties of emergent virulence of the L. infantum POL2FL7 and BOS1FL1 isolates obtained from Phlebotomus perniciosus collected in the outbreak area and compare them with those of the well-characterized strain BCN150 MON-1 isolated from a dog. The P. perniciosus specimens were collected during an entomological survey conducted in the transmission season of 2012. We observed a range of virulence phenotypes from moderately to highly aggressive after 5 weeks of infection. IV challenge of mice with outbreak isolates from sand flies induced higher splenic and liver parasite burdens, higher serological titres of specific anti-Leishmania antibodies and impaired capacities to control infection, as revealed by the arginine metabolism and low ratios of Th1/Th2 cytokine profiles analysed, compared with the corresponding measures evaluated in mice infected with the BCN150 strain. The BOS1FL1 isolate showed the highest degree of virulence among the isolates, superior to that of POL2FL7, as evidenced by the analysed biomarkers and the histopathological severity of liver lesions. These results provide insight into how L. infantum isolates from sand flies collected in the outbreak area have been able to affect not only immunosuppressed patients but also middle-aged people with normal immunocompetence in the largest human VL outbreak in Europe.

Raccoons (Procyon lotor) in the Madrid region of Spain are carriers of antimicrobial-resistant Escherichia coli and enteropathogenic E. coli.

The role of wildlife in the epidemiology of antimicrobial resistance is unclear. Raccoons in North America can carry a variety of enteric bacteria, with associated antimicrobial resistance, that could infect humans and livestock. The potential for raccoons to carry these bacteria in Europe, where they are an invasive species, has not been explored. Our objectives were to determine the prevalence of Escherichia coli with associated antimicrobial resistance in raccoons from the Madrid region of Spain and to determine whether they are carriers of potential human pathogens, including verotoxin-producing E. coli (VTEC) and enteropathogenic E. coli (EPEC). In total, we tested 237 E. coli isolates from the faeces of 83 euthanized raccoons for susceptibility to 14 antimicrobial agents and the presence of VTEC and EPEC. Antimicrobial resistance to at least one antimicrobial was detected in the faeces of 51% (42/83; 95% CI, 40.1-61.1) of the raccoons tested. A high percentage of raccoons carried, in their faeces, E. coli isolates resistant to ampicillin (33%), streptomycin (33%), tetracycline (30%), sulphafurazole (31%) and trimethoprim-sulphamethoxazole (23%). We detected one isolate of extended-spectrum ß-lactamase-producing E. coli from the faeces of one raccoon. We detected VTEC in the faeces of one raccoon, and EPEC in the faeces of 12% (10/83) of the raccoons. Of the raccoons that carried EPEC in their faeces, 60% (6/10) carried EPEC isolates that exhibited characteristics associated with pathogenicity in humans. Raccoons in Madrid can carry pathogenic and antimicrobial-resistant E. coli in their faeces and may be a risk to public health because of their potential to contaminate food and the environment with their faeces.

Should We Base Training Prescription on the Force-Velocity Profile? Exploratory Study of Its Between-Day Reliability and Differences Between Methods.

PURPOSE: To analyze the differences in the force-velocity (F-v) profile assessed under unconstrained (ie, using free weights) and constrained (ie, on a Smith machine) vertical jumps, as well as to determine the between-day reliability. METHODS: A total of 23 trained participants (18 [1] y) performed an incremental load squat jump test (with ∼35%, 45%, 60%, and 70% of the subjects' body mass) on 2 different days using free weights and a Smith machine. Nine of these participants repeated the tests on 2 other days for an exploratory analysis of between-day reliability. F-v variables (ie, maximum theoretical force [F0], velocity [v0], and power, and the imbalance between the actual and the theoretically optimal F-v profile) were computed from jump height. RESULTS: A poor agreement was observed between the F-v variables assessed under constrained and unconstrained conditions (intraclass correlation coefficient [ICC] < .50 for all). The height attained during each single jump performed under both constrained and unconstrained conditions showed an acceptable reliability (coefficient of variation < 10%, ICC > .70). The F-v variables computed under constrained conditions showed an overall good agreement (ICC = .75-.95 for all variables) and no significant differences between days (P > .05), but a high variability for v0, the imbalance between the actual and the theoretically optimal F-v profile, and maximal theoretical power (coefficient of variation = 17.0%-27.4%). No between-day differences were observed for any F-v variable assessed under unconstrained conditions (P > .05), but all of the variables presented a low between-day reliability (coefficient of variation > 10% and ICC < .70 for all). CONCLUSIONS: F-v variables differed meaningfully when obtained from constrained and unconstrained loaded jumps, and most importantly seemed to present a low between-day reliability.

A further investigation of the leishmaniosis outbreak in Madrid (Spain): low-infectivity phenotype of the Leishmania infantum BOS1FL1 isolate to establish infection in canine cells.

Human leishmaniosis caused by Leishmania infantum is a zoonotic disease, with dogs as the main reservoir in Mediterranean Basin countries. The largest European outbreak of human leishmaniosis declared in the southwestern Madrid region (Spain) is characterized by unusual epidemiological and clinical features, such as the emergence of new wild reservoirs (hares and rabbits), whereas the seroprevalence, infection, and severity of canine leishmaniosis have not substantially changed since the first studies conducted in Madrid before the outbreak. Previous studies reported that L. infantum isolates from the Madrid leishmaniosis focus displayed elevated virulence in in vivo models of infection and increased infectivity in murine target cells. With the aim of studying whether changes in the host-parasite interaction and virulence profile have developed, we first assessed the behaviour of one circulating isolate of the outbreak, IPER/ES/2012/BOS1FL1 (BOS1FL1), compared to that of a well-characterized strain from canine leishmaniosis, MCAN/ES/1996/BCN150 (BCN150), in terms of infection capacity (percentage of infected cells, representing infectivity, and number of amastigotes per infected cell, representing the intensity of infection) in canine monocytes and macrophages. BCN150 displayed significantly higher infectivity (76.82 ±â€¯4.40 vs 38.58 ±â€¯2.19; P <  0.0001) and intensity of infection (3.64 ± 0.13 vs 1.83 ±â€¯0.12; P <  0.0001) than BOS1FL1 when interacting with canine cells. Our ROS induction results did not differ significantly between the two isolates or with the responses previously described for other L. infantum isolates. Paradoxically, increased resilience to hydrogen peroxide exposure was observed for BOS1FL1 (% viability 40.62 ±â€¯5.54 vs 26.37 ±â€¯2.93; P = 0.039). Finally, we demonstrated that a decreased intracellular load of BOS1FL1 was associated with increased IFN-γ (261.21 ±â€¯26.29 vs 69.80 ±â€¯9.02; P = 0.0151) and decreased IL-10 production (165.06 ±â€¯23.87 vs 264.41 ±â€¯30.58; P = 0.0002). In this study, we provide the first detailed insight into the differences between the isolate BOS1FL1 from the outbreak in Madrid and the well-characterized strain BCN150 MON-1 obtained from a dog in their response to interacting with canine cells. However, further studies are necessary to shed light on the immune mechanisms resulting in BOS1FL1 exhibiting less virulent behaviour in canine cells than in cells derived from other host species.

Epitope Selection for Fighting Visceral Leishmaniosis: Not All Peptides Function the Same Way.

Visceral leishmaniosis (VL) caused by Leishmania infantum is a disease with an increasing prevalence worldwide. Treatments are expensive, toxic, and ineffective. Therefore, vaccination seems to be a promising approach to control VL. Peptide-based vaccination is a useful method due to its stability, absence of local side effects, and ease of scaling up. In this context, bioinformatics seems to facilitate the use of peptides, as this analysis can predict high binding affinity epitopes to MHC class I and II molecules of different species. We have recently reported the use of HisAK70 DNA immunization in mice to induce a resistant phenotype against L. major, L. infantum, and L. amazonensis infections. In the present study, we used bioinformatics tools to select promising multiepitope peptides (HisDTC and AK) from the polyprotein encoded in the HisAK70 DNA to evaluate their immunogenicity in the murine model of VL by L. infantum. Our results revealed that both multiepitope peptides were able to induce the control of VL in mice. Furthermore, HisDTC was able to induce a better cell-mediated immune response in terms of reduced parasite burden, protective cytokine profile, leishmanicidal enzyme modulation, and specific IgG2a isotype production in immunized mice, before and after infectious challenge. Overall, this study indicates that the HisDTC chimera may be considered a satisfactory tool to control VL because it is able to activate a potent CD4+ and CD8+ T-cell protective immune responses.

Cumulative effects of triadic closure and homophily in social networks.

Social network structure has often been attributed to two network evolution mechanisms-triadic closure and choice homophily-which are commonly considered independently or with static models. However, empirical studies suggest that their dynamic interplay generates the observed homophily of real-world social networks. By combining these mechanisms in a dynamic model, we confirm the longheld hypothesis that choice homophily and triadic closure cause induced homophily. We estimate how much observed homophily in friendship and communication networks is amplified due to triadic closure. We find that cumulative effects of homophily amplification can also lead to the widely documented core-periphery structure of networks, and to memory of homophilic constraints (equivalent to hysteresis in physics). The model shows that even small individual bias may prompt network-level changes such as segregation or core group dominance. Our results highlight that individual-level mechanisms should not be analyzed separately without considering the dynamics of society as a whole.

Strength and medium-term impact of HisAK70 immunization in dogs: Vaccine safety and biomarkers of effectiveness for ex vivo Leishmania infantum infection.

HisAK70 candidates have successfully been tested in cutaneous (CL) and visceral leishmaniosis (VL) mouse models. Here, we analyse different biomarkers in dog trials after a heterologous immunization strategy with a HisAK70 candidate (plasmid DNA plus adoptive transfer of peripheral blood-derived dendritic cells (DCs) pulsed with the same pathoantigen and CpG ODN as an adjuvant) to explore the antileishmanial activity in an ex vivo canine co-culture system in the presence of Leishmania infantum parasites. In the canine model, the heterologous HisAK70 vaccine could decrease the infection index in the DC-T cell co-culture system by up to 54% after 30 days and reach almost 67% after 100 days post-immunization, respectively, compared to those obtained in the control group of dogs. The observed security and potential to fight ex vivo L. infantum infection highlight a HisAK70 heterologous immunization strategy as a promising alternative to evaluate its effectiveness against canine VL.