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Abstract Unregulated, systemic inflammation negatively impacts health and production in dairy cows. Soluble mediators and platelets have been studied for their expansive role in mediating inflammation. Our objectives were to compare the plasma oxylipin and endocannabinoid profiles, and the platelet and plasma proteomic profiles of healthy cows to cows experiencing elevated systemic inflammation as indicated by plasma haptoglobin (Hp) concentrations. Postpartum cows at 3 DIM with plasma Hp concentrations $$\:\ge\:$$ 0.50 g/L and no clinical disease were enrolled into the high-inflammation group (n = 8). Cows with plasma Hp concentrations $$\:\le\:$$ 0.1 g/L and no clinical disease were enrolled into the low-inflammation group (n = 8). Targeted lipidomic analysis revealed differences in the plasma oxylipin and endocannabinoid profile between high- and low-inflammation cows. Cows in the high-inflammation group had increased plasma concentrations of the oxylipins 9(S)-HpOTrE, 9(S)-HOTrE, 13(S)-HpOTrE, and 9,10-EpOME, and the endocannabinoid anandamide. In-depth proteomic analysis of platelets between the high- and low-inflammation groups revealed significant differences in protein categories related to platelet granule release and cellular iron uptake. Proteomic outputs from plasma revealed 24 proteins to be different between high and low-inflammation groups, including proteins involved in autophagy and immune mediation. Together, our results indicate that cows experiencing an exacerbated systemic inflammatory response in the postpartum may have impaired disease resistance, and platelets could be contributors to their inflammatory state.

Exposure to environmental contaminants can result in profound effects on the host immune system. One class of environmental toxicants, known as dioxins, are persistent environmental contaminants termed “forever chemicals”. The archetype toxicant from this group of chemicals is 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), an immunotoxicant that activates the aryl-hydrocarbon receptor pathway leading to a variety of changes in immune cell responses. Immune cell functions are crucial to the development and maintenance of healthy reproduction. Immune cells facilitate tolerance between at the maternal-fetal interface between the parent and the semi-allogenic fetus and help defend the gravid reproductive tract from infectious assault. Epidemiological studies reveal that exposure to environmental contaminants (such as TCDD) are linked to adverse reproductive health outcomes including endometriosis, placental inflammation, and preterm birth. However, little is known about the molecular mechanisms that underpin how environmental toxicant exposures impact immune functions at the maternal-fetal interface or within the reproductive tract in general. This review presents the most recent published work that studies interactions between dioxin or TCDD exposure, the host immune system, and reproduction.

Magnetorotational instability (MRI) is one of the fundamental processes in astrophysics, driving angular momentum transport and mass accretion in a wide variety of cosmic objects. Despite much theoretical/numerical and experimental efforts over the last decades, its saturation mechanism and amplitude, which sets the angular momentum transport rate, remains not well understood, especially in the limit of high resistivity, or small magnetic Prandtl numbers typical to interiors (dead zones) of protoplanetary disks, liquid cores of planets and liquid metals in laboratory. Using direct numerical simulations, in this paper we investigate the nonlinear development and saturation properties of the helical magnetorotational instability (HMRI)—a relative of the standard MRI—in a magnetized Taylor–Couette flow at very low magnetic Prandtl number (correspondingly at low magnetic Reynolds number) relevant to liquid metals. For simplicity, the ratio of azimuthal field to axial field is kept fixed. From the linear theory of HMRI, it is known that the Elsasser number, or interaction parameter determines its growth rate and plays a special role in the dynamics. We show that this parameter is also important in the nonlinear problem. By increasing its value, a sudden transition from weakly nonlinear, where the system is slightly above the linear stability threshold, to strongly nonlinear, or turbulent regime occurs. We calculate the azimuthal and axial energy spectra corresponding to these two regimes and show that they differ qualitatively. Remarkably, the nonlinear state remains in all cases nearly axisymmetric suggesting that this HMRI-driven turbulence is quasi two-dimensional in nature. Although the contribution of non-axisymmetric modes increases moderately with the Elsasser number, their total energy remains much smaller than that of the axisymmetric ones.

Abstract Future state prediction for nonlinear dynamical systems is a challenging task. Classical prediction theory is based on a, typically long, sequence of prior observations and is rooted in assumptions on statistical stationarity of the underlying stochastic process. These algorithms have trouble predicting chaotic dynamics, “Black Swans” (events which have never previously been seen in the observed data), or systems where the underlying driving process fundamentally changes. In this paper we develop (1) a global and local prediction algorithm that can handle these types of systems, (2) a method of switching between local and global prediction, and (3) a retouching method that tracks what predictions would have been if the underlying dynamics had not changed and uses these predictions when the underlying process reverts back to the original dynamics. The methodology is rooted in Koopman operator theory from dynamical systems. An advantage is that it is model-free, purely data-driven and adapts organically to changes in the system. While we showcase the algorithms on predicting the number of infected cases for COVID-19 and influenza cases, we emphasize that this is a general prediction methodology that has applications far outside of epidemiology.

The magnetorotational instability (MRI) is thought to be a powerful source of turbulence and momentum transport in astrophysical accretion discs, but obtaining observational evidence of its operation is challenging. Recently, laboratory experiments of Taylor–Couette flow with externally imposed axial and azimuthal magnetic fields have revealed the kinematic and dynamic properties of the MRI close to the instability onset. While good agreement was found with linear stability analyses, little is known about the transition to turbulence and transport properties of the MRI. We here report on a numerical investigation of the MRI with an imposed azimuthal magnetic field. We show that the laminar Taylor–Couette flow becomes unstable to a wave rotating in the azimuthal direction and standing in the axial direction via a supercritical Hopf bifurcation. Subsequently, the flow features a catastrophic transition to spatio-temporal defects which is mediated by a subcritical subharmonic Hopf bifurcation. Our results are in qualitative agreement with the PROMISE experiment and dramatically extend their realizable parameter range. We find that as the Reynolds number increases defects accumulate and grow into turbulence, yet the momentum transport scales weakly.

Leishmaniasis encompasses a group of neglected diseases caused by flagellated protozoa belonging to the Leishmania genus, associated with high morbidity and mortality. The search for compounds with anti-Leishmania activity that exhibit lower toxicity and can overcome the emergence of resistant strains remains a significant goal. In this context, the calpain inhibitor MDL28170 has previously demonstrated deleterious effects against promastigote forms of Leishmania amazonensis, which led us to investigate its role on axenic amastigote forms. The calpain inhibitor MDL28170 was able to decrease the viability of amastigotes in a typically dose-dependent manner. The treatment with the IC50 dose (13.5 μM) for 72 h led to significant amastigote lysis and increased cell-to-cell aggregation. Ultrastructural analysis revealed several cellular alterations, including disruption of the trans-Golgi network and the formation of autophagosomes when treated with MDL28170 at ½ × IC50 dose. Additionally, mitochondrial swelling and the formation of concentric membranous structures inside the mitochondrion were observed after incubation with the IC50 dose. These results reinforce the potential application of the calpain inhibitor MDL28170 against L. amazonensis, highlighting its effectiveness and possible mechanism of action against the parasite.

Wiskott-Aldrich syndrome (WAS) is a severe X-linked primary immunodeficiency resulting from a diversity of mutations distributed across all 12 exons of the WAS gene. WAS encodes a hematopoietic-specific and developmentally regulated cytoplasmic protein (WASp). The objective of this study was to develop a gene correction strategy potentially applicable to most WAS patients by employing nuclease-mediated, site-specific integration of a corrective WAS gene sequence into the endogenous WAS chromosomal locus. In this study, we demonstrate the ability to target the integration of WAS2-12-containing constructs into intron 1 of the endogenous WAS gene of primary CD34+ hematopoietic stem and progenitor cells (HSPCs), as well as WASp-deficient B cell lines and WASp-deficient primary T cells. This intron 1 targeted integration (TI) approach proved to be quite efficient and restored WASp expression in treated cells. Furthermore, TI restored WASp-dependent function to WAS patient T cells. Edited CD34+ HSPCs exhibited the capacity for multipotent differentiation to various hematopoietic lineages in vitro and in transplanted immunodeficient mice. This methodology offers a potential editing approach for treatment of WAS using patient’s CD34+ cells.

Introduction: Cytological samples obtained by endobronchial ultrasound (EBUS) are capital for diagnosis, staging and molecular profile in non-small cell lung carcinoma (NSCLC). Objective: To assess the success rate of complete, partial and individual of molecular analysis in samples obtained by EBUS-guided transbronchial needle aspiration (TBNA) and/or by oesophageal ultrasound-guided fine needle aspiration with an echobronchoscope (EUS-B-FNA) in patients with NSCLC. Methods: Prospective study including 90 patients with non-squamous NSCLC, or non-smoking squamous. Cytological samples were classified into two groups. Group 1: PEN membrane slide and/or cell blocks for the determination of mutations of EGFR, KRAS, ERBB2 and BRAF. Group 2: silane coated slides or cell blocks for rearrangements of ALK, ROS1 and MET amplification. Results: The success rate was 78.6% for 4 molecular alterations (EGFR, KRAS, ALK and ROS1), and 44% for 7 determinations. The individual success rate for EGFR was 97%, KRAS 96.3%, ALK 85%, ROS1 82.3%, ERBB2 71.4%, BRAF 67.7% and MET 81.1%. There were no significant differences (p = 0.489) in the number of molecular analyses (1–3 vs. 4) in group 1, depending on the types of samples (cell block vs. PEN membrane slide vs. cell block and PEN membrane slide). Conclusions: In patients with NSCLC, the cytological material obtained by ultrasound-guided needle aspiration is sufficient for individual and partial molecular analysis in the vast majority of cases. Membrane slides such as cell blocks are valid samples for molecular analysis.

The wide range of symptoms of the coronavirus disease 2019 (COVID-19) makes it challenging to predict the disease evolution using a single parameter. Therefore, to describe the pathophysiological response to SARS-CoV-2 infection in hospitalized patients with severe COVID-19, we compared according to survival or death, the sociodemographic and clinical characteristics, the biochemical and immunological attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectra from saliva samples and their correlation with chemometric findings. Herein, we demonstrate that ATR-FTIR spectroscopy allows the description of the events related to cell damage, such as lipids biogenesis and the secondary structure of proteins associated with lactate dehydrogenase and albumin levels. Moreover, humoral (IgM) and cellular (IFN-γ, TNF-α, IL-10, and IL-6) responses were also increased in patients who died from COVID-19.

Human African trypanosomiasis (also known as sleeping sickness, with Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense as etiological agents), American trypanosomiasis (also known as Chagas disease, with Trypanosoma cruzi as the etiological agent), and leishmaniasis (including cutaneous, mucocutaneous, and visceral forms, with multiple species belonging to the Leishmania genus as etiological agents) are recognized as neglected tropical diseases (NTDs) [...]

Chagas disease is an emerging and neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, estimated to infect 8 to 10 million people worldwide, according to the World Health Organization [...]

Background Previous studies in patients with ST-segment elevation acute myocardial infarction treated with primary angioplasty and supported by the PiCSO® system have shown a modest yet significant absolute reduction in the infarcted myocardial area. However, the simultaneous use of PiCSO® and Impella CP® during high-risk percutaneous coronary intervention (PCI) procedures has not been reported. Case summary A 76-year-old Caucasian man presented with severe and highly calcified left main coronary disease and severely depressed left ventricular function. As coronary bypass surgery was deemed prohibitive, successful PCI was performed with the simultaneous use of PiCSO® and Impella CP® to mitigate damage from distal microembolization and provide mechanical circulatory support to the left ventricle during the high-risk PCI procedure. Discussion Our case exemplifies for the first time the simultaneous use of PiCSO® and Impella CP® during a high-risk PCI. This case suggests the feasibility and safety of combining both devices for mechanical haemodynamic and microcirculatory support simultaneously in specific cases during high-risk PCI, offering hope for reducing post-PCI myocardial damage in a selected population of patients. [ABSTRACT FROM AUTHOR]

Abstract Background The family Trypanosomatidae encompasses parasitic flagellates, some of which cause serious vector-transmitted diseases of humans and domestic animals. However, insect-restricted parasites represent the ancestral and most diverse group within the family. They display a range of unusual features and their study can provide insights into the biology of human pathogens. Here we describe Vickermania, a new genus of fly midgut-dwelling parasites that bear two flagella in contrast to other trypanosomatids, which are unambiguously uniflagellate. Results Vickermania has an odd cell cycle, in which shortly after the division the uniflagellate cell starts growing a new flagellum attached to the old one and preserves their contact until the late cytokinesis. The flagella connect to each other throughout their whole length and carry a peculiar seizing structure with a paddle-like apex and two lateral extensions at their tip. In contrast to typical trypanosomatids, which attach to the insect host’s intestinal wall, Vickermania is separated from it by a continuous peritrophic membrane and resides freely in the fly midgut lumen. Conclusions We propose that Vickermania developed a survival strategy that relies on constant movement preventing discharge from the host gut due to intestinal peristalsis. Since these parasites cannot attach to the midgut wall, they were forced to shorten the period of impaired motility when two separate flagella in dividing cells interfere with each other. The connection between the flagella ensures their coordinate movement until the separation of the daughter cells. We propose that Trypanosoma brucei, a severe human pathogen, during its development in the tsetse fly midgut faces the same conditions and follows the same strategy as Vickermania by employing an analogous adaptation, the flagellar connector.

The demands on transportation systems continue to grow while the methods for analyzing and forecasting traffic conditions remain limited. Here the authors show a parameter-independent approach for an accurate description, identification and forecasting of spatio-temporal traffic patterns directly from data.

Phytomonas serpens is a protozoan parasite that alternates its life cycle between two hosts: an invertebrate vector and the tomato fruit. This phytoflagellate is able to synthesize proteins displaying similarity to the cysteine peptidase named cruzipain, an important virulence factor from Trypanosoma cruzi, the etiologic agent of Chagas disease. Herein, the growth of P. serpens in complex medium (BHI) supplemented with natural tomato extract (NTE) resulted in the increased expression of cysteine peptidases, as verified by the hydrolysis of the fluorogenic substrate Z-Phe-Arg-AMC and by gelatin-SDS-PAGE. Phytoflagellates showed no changes in morphology, morphometry and viability, but the proliferation was slightly reduced when cultivated in the presence of NTE. The enhanced proteolytic activity was accompanied by a significant increase in the expression of cruzipain-like molecules, as verified by flow cytometry using anti-cruzipain antibodies. In parallel, parasites incubated under chemically defined conditions (PBS supplemented with glucose) and added of different concentration of NTE revealed an augmentation in the production of cruzipain-like molecules in a typically dose-dependent way. Similarly, P. serpens recovered from the infection of mature tomatoes showed an increase in the expression of molecules homologous to cruzipain; however, cells showed a smaller size compared to parasites grown in BHI medium. Furthermore, phytoflagellates incubated with dissected salivary glands from Oncopeltus fasciatus or recovered from the hemolymph of infected insects also showed a strong enhance in the expression of cruzipain-like molecules that is more relevant in the hemolymph. Collectively, our results showed that cysteine peptidases displaying similarities to cruzipain are more expressed during the life cycle of the phytoflagellate P. serpens both in the invertebrate and plant hosts.

Myeloid sarcomas can be detected in up to 30% of acute myeloid leukemia cases or occur de-novo without bone marrow involvement. The most frequent localization of myeloid sarcomas in the abdominal cavity is the small intestine, and gastric presentations are infrequent, frequently misdiagnosed, and a high level of suspicion should exist when the characteristic histomorphology features are present. The current review features a case report with gastric presentation of myeloid sarcoma in a patient with a diagnosis of acute myeloid leukemia with trisomy 8. In addition, a review of the literature of intestinal type myeloid sarcomas shows that less than 15% of these cases have been reported in the stomach. The most common molecular aberrancy detected in intestinal myeloid sarcomas is the fusion protein CBFB-MYH11. Review of several large studies demonstrates that the presence of myeloid sarcoma does not constitute an independent prognostic factor. The therapeutic approach will be tailored to the specific genetic abnormalities present, and systemic chemotherapy with hematopoietic stem cell transplant are the most efficient strategies.

HIV-1 is characterized by its ability to mutate and recombine even at polymerase (pol) gene. However, pol-gene diversity is limited due to functional constraints. The aim of this study was to characterize longitudinally, by next-generation sequencing (NGS), HIV-1 variants based on pol-gene sequences, at intra- and inter-host level, from acute/early to chronic stages of infection, in the absence of antiretroviral therapy. Ten men who have sex with men (MSM) were recruited during primary infection and yearly followed for five years. Even after a maximum of a five-year follow-up period, the phylogenetic analysis of HIV-1 pol-gene sequences showed a host-defined structured pattern, with a predominance of purifying selection forces during the follow-up. MSM had been acutely infected by different HIV-1 variants mainly ascribed to pure subtype B, or BF recombinant variants and showed different genetic mosaicism patterns that last until the chronic stage, representing a major challenge for prevention strategies.

Objective To determine the association between endoplasmic reticulum aminopeptidase (ERAP)1 and ERAP2 single-nucleotide polymorphisms (SNPs) and human leukocyte antigens (HLA)-B27+ or HLA-B15+ patients with spondyloarthritis (SpA).Methods 104 patients with SpA according to Assessment of Spondyloarthritis International Society criteria were included in the study. HLA typing was performed by PCR. The polymorphisms were determined by real-time PCR on genomic DNA using customised probes for SNPs rs27044, rs17482078, rs10050860 and rs30187 in ERAP1, and rs2910686, rs2248374 and rs2549782 in ERAP2.Results 70 of the104 patients with SpA were HLA-B27+ and 34 were HLA-B15+. The distribution of ERAP1 and ERAP2 SNPs between the HLA-B15+ and HLA-B27+ patients with SpA did not reveal differences. Likewise, no differences in the frequencies of ERAP1 SNP haplotypes and alleles HLA-B15 or HLA-B27 were found. Interestingly, however, the frequencies of three particular haplotypes formed by ERAP2 SNPs rs2549782/rs2248374/rs2910686 varied between HLA-B15+ and HLA-B27+ patients: the ERAP2 SNPs haplotype TGT was more common in HLA-B15+ patients with SpA (OR 2.943, 95% CI 1.264 to 6.585; P=0.009), whereas the ERAP2 SNP haplotypes TGC and CAT were more associated with HLA-B27+ patients with SpA: (OR 4.483, 95% CI 1.524 to 13.187; p=0.003) and (OR 9.014, 95% CI 1.181 to 68.807; p=0.009), respectively.Conclusion An association was found between HLA-B15+ patients with SpA and haplotype TGT of ERAP2 SNPs. On the other hand, HLA-B27+ patients with SpA were associated with ERAP2 haplotypes TGC and CAT. These associations could be related to the clinical presentation of the disease, specifically with a peripheral or axial predominance, respectively.

The necessity of drug combinations to treat leishmaniasis came to the surface mainly because of the toxicity of current treatments and the emergence of resistant strains. The calpain inhibitor MDL28170 has previously shown anti-Leishmania activity, therefore its use in association with standard drugs could provide a new alternative for the treatment strategy against leishmaniasis. In this study, we analyzed the potential of the combination of MDL28170 and the antileishmanial drug amphotericin B against Leishmania amazonensis and Leishmania chagasi. The compounds were tested in the combination of the ½ × IC50 value of MDL28170 plus the ¼ × IC50 value of amphotericin B, which led to an increment in the anti-promastigote activity when compared to the single drug treatments. This drug association revealed several and severe morphophysiological changes on parasite cells, such as loss of plasma membrane integrity, reduced size of flagellum, and depolarization of mitochondrial membrane potential besides increased reactive oxygen species production. In addition, the combination of both drugs had a deleterious effect on the Leishmania–macrophage interaction, reflecting in a significant anti-amastigote action, which achieved a reduction of 50% in the association index. These results indicate that the combination treatment proposed here may represent a new alternative for leishmaniasis chemotherapy.

This article describes a study in which modellers were challenged to compute the wind field at a forested site with moderately complex topography. The task was to model the wind field in stationary conditions with neutral stratification by using the wind velocity measured at 100 m at a metmast as the only reference. Detailed maps of terrain elevation and forest densities were provided as the only inputs, derived from airborne laser scans (ALSs) with a resolution of 10 m × 10 m covering an area of 50 km × 50 km, that closely match the actual forest and elevation of the site. The participants were free to apply their best practices for the simulation to decide the size of the domain, the value of the geostrophic wind, and every other modelling parameter. The comparison of the results with the measurements is shown for the vertical profiles of wind speed, shear, wind direction, and turbulent kinetic energy. The ALS-based data resulted in reasonable agreement of the wind profile and turbulence magnitude. The best performance was found to be that of large-eddy simulations using a very large domain. For the Reynolds-averaged Navier–Stokes type of models, the constants in the turbulence closure were shown to have a great influence on the yielded turbulence level, but were of much less importance for the wind speed profile. Of the variety of closure constants used by the participating modellers, the closure constants from Sogachev and Panferov (2006) proved to agree best with the measurements. Particularly the use of Cμ≈0.03 in the k–ε model obtained better agreement with turbulence level measurements. All except two participating models used the full detailed ground and forest information to model the forest, which is considered significant progress compared to previous conventional approaches. Overall, the article gives an overview of how well different types of models are able to capture the flow physics at a moderately complex forested site.

Mesenchymal stem/stromal cells (MSCs) exhibit multidifferentiation potential, paralleled with immunomodulatory and trophic properties that make them viable alternative tools for the treatment of degenerative disorders, allograft rejection, autoimmune diseases, and tissue regeneration. MSC functional attributes can be modulated by exposing them to inflammatory-stimulating microenvironments (i.e., priming) before their therapeutic use. Granulocyte-colony stimulating factor (G-CSF) is a cytokine that plays key roles in immune response and hematopoiesis modulation through direct effects on hematopoietic progenitors’ proliferation, survival, and mobilization. Despite the established roles of MSCs supporting hematopoiesis, the effects of G-CSF on MSCs biology have not been thoroughly explored. This study reveals that G-CSF has also direct effects on adipose-derived MSCs (ADSCs), modulating their functions. Herein, microarray-based transcriptomic analysis shows that G-CSF stimulation in vitro results in modulation of various signaling pathways including ones related with the metabolism of hyaluronan (HA), conferring a profile of cell mobilization to ADSCs, mediated in a cell-intrinsic fashion in part by reducing CD44 expression and HA synthesis-related genes. Collectively, these data suggest a direct modulatory effect of G-CSF on ADSC function, potentially altering their therapeutic capacity and thus the design of future clinical protocols.

Brucellosis is a zoonosis of nearly worldwide distribution. The disease is considered to be endemic in most of the developing countries with a substantial impact on both human and animal health as well as on the economy. The aim of this scoping review is to provide an overview of the brucellosis status in Colombia and the factors associated with its persistence, to highlight the strengths and gaps of the adopted countermeasures and to supply evidence to policy-makers on the best approaches to mitigate the disease burden. Due to the presence of brucellosis in several susceptible production livestock systems scattered throughout the country, a plan for its control, prevention and eradication was established almost 20 years ago. However, despite extensive efforts, brucellosis prevalence has fluctuated over the years without any trend of decreasing. The restricted budget allocated for brucellosis control is a limiting factor for the success of the program. For instance, the absence of indemnities for farmers results in infected animals remaining on farms which potentially increases the risk of disease spread. Likewise, disease surveillance is restricted to Brucella abortus and excludes other Brucella species of importance, such as B. melitensis and B. suis. The countermeasures are mostly focused on cattle and only a few actions are in place for the management of brucellosis in other livestock species. In humans, cases of brucellosis are annually diagnosed, although the disease remains highly underreported. High impact educational and training programs are required to address the disease in a comprehensive manner, including vulnerable groups, such as traditional smallholders and low-productivity regions, as well as other stakeholders, such as healthcare and veterinary authorities. Important financial investments based on sustained cooperation between governmental institutions, industry, and farmers are important for developing affordable and effective strategies to control the disease.

Concurrently, leishmaniasis and AIDS are global public health issues and the overlap between these diseases adds additional treats to the management of co-infected patients. Lopinavir (LPV) has a well characterized anti-HIV and leishmanicidal action, and to analyze its combined action with miltefosine (MFS) could help to envisage strategies to the management of co-infected patients. Here, we evaluate the interaction between LPV and MFS against Leishmania infantum infection by in vitro and in vivo approaches. The effect of the compounds alone or in association was assessed for 72 h in mouse peritoneal macrophages infected with L. infantum by the determination of the IC50s and FICIs. Subsequently, mice were orally treated twice daily during 5 days with the compounds alone or in association and evaluated after 30 days. The in vitro assays revealed an IC50 of 0.24 μM and 9.89 μM of MFS and LPV, respectively, and an additive effect of the compounds (FICI 1.28). The in vivo assays revealed that LPV alone reduced the parasite load in the spleen and liver by 52 and 40%, respectively. The combined treatment of infected BALB/c mice revealed that the compounds alone required at least two times higher doses than when administered in association to virtually eliminate the parasite. Mice plasma biochemical parameters assessed revealed that the combined therapy did not present any relevant hepatotoxicity. In conclusion, the association of MFS with LPV allowed a reduction in each compound concentration to achieve the same outcome in the treatment of visceral leishmaniasis. Although a pronounced synergistic effect was not evidenced, it does not discard that such combination could be useful in humans co-infected with HIV and Leishmania parasites.

Two psychrophilic bacterial samples were isolated from King George Island soil, in Antarctica. The phylogenetic analysis based on the 16S rRNA (rrs) gene led to the correlation with the closest related isolates as Sporosarcina aquimarina (99%) and Algoriphagus antarcticus(99%), with query coverage of 99% and 98%, respectively.The spent culture media from both isolates displayed proteolytic activities detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis containing gelatin as protein substrate. Under the employed conditions, S. aquimarina showed a 55 kDa protease with the best activity detected at pH 7.0 and at 27°C. A. antarcticusalso showed a single extracellular protease, however its molecular mass was around 90kDa and its best activity was detected at pH 9.0 and at 37°C. The proteases from both isolates were inhibited by 1,10-phenanthroline and EDTA, two metalloprotease inhibitors. This is the first record of protease detection in both species, and our results may contribute to broaden the basic knowledge of proteases from the Antarctica environment and may help prospecting future biotechnological applications of these enzymes.

A number of studies have proposed an anti-diabetic effect for tarchonanthuslactone based on its structural similarity with caffeic acid, a compound known for its blood glucose-reducing properties. However, the actual effect of tarchonanthuslactone on blood glucose level has never been tested. Here, we report that, in opposition to the common sense, tarchonanthuslactone has a glucose-increasing effect in a mouse model of obesity and type 2 diabetes mellitus. The effect is acute and non-cumulative and is present only in diabetic mice. In lean, glucose-tolerant mice, despite a slight increase in blood glucose levels, the effect was not significant.