Modulatory Action Research Articles

Mutual action of self-phase modulation and cross-phase modulation on the parametric four-photon mixing. Exact analytical solutions in the form of Jacobi functions

The purpose of this work is to investigate the influence of the self-phase modulation and cross-phase modulation on the parametric interaction between pump signal and idler at few coherent lengths. The coherent length of four-photon mixing process can be quite long, up to 500 m to 1 km, if the spectral separation between the signal waves is relatively small. The problem with generation of new frequencies on distances less than one coherent length in parametric four-photon processes, without including the Raman scatter was solved only in approximation for a fixed electric field or fixed intensity of the pump wave. The overall task which includes the change in intensity and the phase of the pump wave has not been studied in detail in the literature up to now. The main purpose of the present work is to solve the more general problem: the mutual action of all χ(3) nonlinear processes on the parametric four-photon mixing.

Topological Centers and Factorization of Certain Module Actions

Let $A$ be a Banach algebra and $X$ be a Banach $A$-bimodule with the left and right module actions $pi_ell: Atimes Xrightarrow X$ and $pi_r: Xtimes Arightarrow X$, respectively. In this paper, we study the topological centers of the left module action $pi_{ell_n}: Atimes X^{(n)}rightarrow X^{(n)}$ and the right module action $pi_{r_n}:X^{(n)}times Arightarrow X^{(n)}$, which inherit from the module actions $pi_ell$ and $pi_r$, and also the topological centers of their adjoints, from the factorization property point of view, and then, we investigate conditions under which these bilinear maps are Arens regular or strongly Arens irregular.

Genetically-achieved disturbances to the expression levels of TNFSF11 receptors modulate the effects of zoledronic acid on growing mouse skeletons

Zoledronic acid (ZOL), a nitrogen bisphosphonate (N-BP), is currently used to treat and control pediatric osteolytic diseases. Variations in the intensity of the effects and side effects of N-BPs have been reported with no clear explanations regarding their origins. We wonder if such variations could be associated with different levels of RANKL signaling activity in growing bone during and after the treatment with N-BPs. To answer this question, ZOL was injected into neonate C57BL/6J mice with different genetically-determined RANKL signaling activity levels (Opg+/+\\RankTg−, Opg+/+\\RankTg+, Opg+/−\\RankTg−, Opg+/−\\RankTg+, Opg−/−\\RankTg− and Opg−/−\\RankTg+ mice) following a protocol (4 injections from post-natal day 1 to 7 at the dose of 50 μg/kg) that mimics those used in onco-pediatric patients. At the end of pediatric growth (1 and half months) and at an adult age (10 months), the bone morphometric and mineral parameters were measured using μCT in the tibia and skull for the different mice. A histologic analysis of the dental and periodontal tissues was also performed. At the end of pediatric growth, a delay in long bone and skull bone growth, a blockage of tooth eruption, some molar root alterations and a neoplasia-like structure associated with incisor development were found. Interestingly, the magnitude of these side effects was reduced by Opg deficiency (Opg−/−) but increased by Rank overexpression (RankTg). Analysis of the skeletal phenotype at ten months confirmed respectively the beneficial and harmful effects of Opg deficiency and Rank overexpression.These results validated the hypothesis that the RANKL signaling activity level in the bone microenvironment is implicated in the modulation of the response to ZOL. Further studies will be necessary to understand the underlying molecular mechanisms, which will help decipher the variability in the effects of N-BPs reported in the human population. Significant statementsThe present study establishes that in mice the RANKL signaling activity level is a major modulator of the effects and side-effects of bisphosphonates on the individual skeleton during growth. However, the modulatory actions are dependent on the ways in which this level of activity is increased. A decrease in OPG expression is beneficial to the skeletal phenotype observed at the end of growth, while RANK overexpression deteriorates it. Far removed from pediatric treatment, in adults, the skeletal phenotypes initially observed at the end of growth for the different levels of RANKL signaling activity were maintained, although significant improvement was associated only with reductions in OPG expression.

Chronic Isolation Stress Affects Subsequent Crowding Stress-Induced Brain Nitric Oxide Synthase (NOS) Isoforms and Hypothalamic-Pituitary-Adrenal (HPA) Axis Responses

The nitric oxide (NO) pathway in the brain is involved in response to psychosocial stressors. The aim of this study was to elucidate the role of nNOS and iNOS in the prefrontal cortex (PFC), hippocampus (HIP), and hypothalamus (HYPO) during social isolation stress (IS), social crowding stress (CS), and a combined IS + CS. In the PFC, 3 days of CS increased iNOS but not nNOS protein level. In the HIP and HYPO, the levels of nNOS and iNOS significantly increased after 3 days of CS. In the PFC, IS alone (11 days) enhanced iNOS protein level following 3 days of CS and increased nNOS level in the HIP and HYPO after 14 days of CS. By contrast, in the HIP, IS abolished the subsequent CS-induced increase in nNOS in the HIP and strongly elevated iNOS level after 7 days of CS. In the HYPO, prior IS inhibited nNOS protein level induced by subsequent CS for 3 days, but increased nNOS protein level after longer exposure times to CS. Isolation stress strongly upregulated plasma interleukin-1β (IL-1β) and adrenocorticotropic hormone (ACTH) levels while corticosterone (CORT) level declined. We show that the modulatory action of the NO pathway and ACTH/CORT adaptation to chronic social isolation stress is dependent on the brain structure and nature and duration of the stressor. Our results indicate that isolation is a robust natural stressor in social animals; it enhances the NO pathway in the PFC and abolishes subsequent social CS-induced NOS responses in the HIP and HYPO.

Nonlinear dynamics of a two-layer system under the action of spatial temperature modulation of an interfacial heat release

Abstract An influence of a spatial temperature modulation of the heat release/consumption at the interface on nonlinear convective flows in the 47v2 silicone oil–water system, has been investigated. Periodic boundary conditions on the lateral walls, corresponding to an infinite two-layer system, have been considered. Transitions between the flows with different spatial structures, have been studied. It is shown that the spatial modulation can change the sequence of bifurcations and lead to the appearance of new oscillatory regimes. Specifically, pulsating traveling waves changing the direction of propagation, as well as regimes corresponding to period doubling, period-four and period-eight bifurcations, have been obtained.

Localized nonlinear excitations in diffusive memristor-based neuronal networks

We extend the existing ordinary differential equations modeling neural electrical activity to include the memory effect of electromagnetic induction through magnetic flux, used to describe time varying electromagnetic field. Through the multi-scale expansion in the semi-discrete approximation, we show that the neural network dynamical equations can be governed by the complex Ginzburg-Landau equation. The analytical and numerical envelop soliton of this equation are reported. The results obtained suggest the possibility of collective information processing and sharing in the nervous system, operating in both the spatial and temporal domains in the form of localized modulated waves. The effects of memristive synaptic electromagnetic induction coupling and perturbation on the modulated action potential dynamics examined. Large electromagnetic induction coupling strength may contribute to signal block as the amplitude of modulated waves are observed to decrease. This could help in the development of a chemical brain anaesthesia for some brain pathologies.

Acute Atomoxetine Selectively Modulates Encoding of Reward Value in Ventral Medial Prefrontal Cortex.

A recent neurocognitive model of attention-deficit hyperactivity disorder (ADHD) has proposed a primary deficit in reward function as well as in executive function to account for underlying neural substrates of ADHD symptoms. Atomoxetine has been widely used as a non-stimulant medication for ADHD with little abuse liability. Although animal studies have reported that atomoxetine increases extracellular levels of both noradrenaline and dopamine in the prefrontal cortex, which receives input from a mesocorticolimbic pathway involved in reward function, there have been few studies in humans concerning the effects of atomoxetine in terms of reward function. Therefore, we investigated whether a single dose of atomoxetine (acute atomoxetine) affects reward processing in healthy adults. We used functional magnetic resonance imaging and adopted the monetary incentive delay task to separately examine neural responses to monetary reward anticipation in the nucleus accumbens and outcome in the ventral medial prefrontal cortex (vmPFC). The experiment was designed as a randomized, placebo-controlled within-subjects cross-over trial. Fourteen healthy adults completed two series of studies, taking either atomoxetine or placebo. Atomoxetine significantly decreased vmPFC activation during gain outcome compared to placebo. In gain anticipation, however, atomoxetine did not show a significant increase in the nucleus accumbens activation compared with placebo. These results suggest that atomoxetine affects reward value encoding through selective modulation of vmPFC activity related to reward outcome. Therefore, such modulatory action may partly contribute to a therapeutic effect of atomoxetine for a group of ADHD patients with increased activity in vmPFC.

Dynamics of Cognitive Processes in Middle-Aged Women Treated with a Fraction Derived from Hydroponic Teucrium Polium Lamiaceae

The dynamics of psychoemotional state and cognitive processes were studied in middle-aged women before and after 20-day courses of an ethanolic extract of Teucrium polium L. Use of extract decreased psychoemotional tension, which was linked with the modulatory actions of the flavonoids and terpenoids present in the extract on GABAA receptors. Use of extract was followed by improvements in measures of short-term memory, increases in the productivity and concentration of attention, and simultaneous increases in the speeds of information analysis, synthesis, and processing in the higher segments of the CNS. Improvements in cognitive processes appeared to result from the neurotropic actions of phenylpropanoid glycosides present in the extract.

Effects of Homeopathic Phosphorus on Encephalitozoon cuniculi-Infected Macrophages In-Vitro.

Encephalitozoon cuniculi (E. cuniculi), a fungus that acts as an intracellular pathogen, causes a marked neurological syndrome in many host species and is a zoonotic concern. Although no well-established treatment for this syndrome is known, previous successful clinical experience using homeopathic phosphorus has been described in which symptom remission with no mortality occurred in 40/42 animals by means of unknown immunological mechanisms. The latter observation was the main motivation for this study. To verify, in an in-vitro model, if macrophages infected with E. cuniculi can change in function after treatment with different potencies of phosphorus. RAW 264.7 macrophages were infected with E. cuniculi in-vitro and treated with various homeopathic potencies of phosphorus. The vehicle was used as a control solution (0.06% succussed ethanol). After 1 and 24 hours, the following parameters were analyzed: parasite internalization (by the Calcofluor staining method), lysosome activity (by the acridine orange method), cytokine/chemokine production (by the MAGPIX system), and cell ultrastructure. Automatic image analysis was used when applicable, and the experiments were performed in triplicate. Treatment with vehicle alone increased interleukin (IL)-6, tumor necrosis factor alpha and monocyte chemotactic protein -1 production (p ≤ 0.05) and reduced the number of internalized parasites (p ≤ 0.001). A progressive and time-dependent increase in RANTES (regulated on activation, normal T-cell expressed and secreted) and lysosome activity (p ≤ 0.002) was observed only after treatment with the highest potency of phosphorus (Phos 200cH), together with decreased apoptosis rate, intense parasite digestion, and the presence of non-internalized spores. Phos 200 cH has a modulatory action on the activity of infected macrophages, especially a specific increase in RANTES, a key element in the prognosis of E. cuniculi-infected and of immunosuppressed patients bearing infections.

UPLC-MS-ESI-QTOF characterization and evaluation of the antibacterial and modulatory antibiotic activity of Ziziphus joazeiro Mart. aqueous extracts

Plant extracts are defined as complex heterogeneous mixtures composed of diverse active ingredient categories which characterize their bioactivities. Ziziphus joazeiro Mart., belonging to the Rhamnaceae family, is an endemic caatinga species with a wide economic potential and application in medicine. In the search for new antibacterial drugs, due to the manifestation and development of bacterial antibiotic resistance mechanisms, medicinal plants, with their broad pharmacological aspects, have led to the development of several phytomedicines. With this in mind, the objective of the present study was to identify the chemical composition of the Ziziphus joazeiro leaf and stem bark aqueous extracts through the UPLC–QTOF-MS/MS method, as well as to verify their antibacterial and modulatory action. Cold extract maceration was used to prepare the Z. joazeiro leaf and stem bark aqueous extracts (AEL and AEB). The broth microdilution method was used for the antibacterial and modulatory activity evaluations. This study is the first to report on the Ziziphus joazeiro extract analyzes by ultra-performance liquid chromatography. The UPLC-MS-ESI-QTOF analysis revealed compounds already present in the Ziziphus genus. The extracts did not present antibacterial activity, however, they presented significant modulatory activity when combined with antibiotics. The results highlight the need for further detailed compound identification analysis and toxicity evaluation of these extracts.

Синхронизация в турбулентном сферическом течении Куэтта под действием неравномерного вращения

Turbulent flows of viscous incompressible fluid in rotating spherical layer in the presence of synchronization are under consideration. Numerical results are presented. Synchronization of turbulent flow is due to the action of periodical modulation of the angular velocity of inner spherical boundary. The angular velocity of outer spherical boundary is constant. Obtained results were compared with experimental data. The interval of modulation amplitudes was determined where synchronization is followed by intermittency “chaos – chaos”.

Вплив ізатізону та наносрібла SS1000 на ростові процеси, зернову продуктивність та фотосинтез вівса сорту незламний

Вплив ізатізону та наносрібла SS1000 на ростові процеси, зернову продуктивність та фотосинтез вівса сорту незламний

On the stability of some preservers

We study some “almost preserver” problems on von Neumann algebra modules. More precisely, we study (1) maps which “almost preserve” the right or left annihilator; (2) the “almost band preservers” – that is, maps which “almost preserve corners”, and (3) “almost centralizers,” which almost preserve module actions. Under certain conditions, we show that maps of these types are automatically continuous, and can be approximated by maps which precisely preserve these relations; often, the operators from the latter class are multiplication operators.

Fruit Bagasse Phytochemicals from Malpighia Emarginata Rich in Enzymatic Inhibitor with Modulatory Action on Hemostatic Processes.

Agro-industrial wastes are promising sources of phytochemicals for the development of products to be used in health promotion and maintenance. In this study, extracts from acerola bagasse (AB) were characterized by HPLC, and evaluated according to its modulatory action on phospholipases A2 and proteases involved in processes such as inflammation and blood clotting. Snake venoms were used as biological tools once they have high functional and structural homology between their enzymes and human enzymes. Two types of extracts were prepared from AB: aqueous and methanolic. These extracts, evaluated at different proportions (venom:extract, w:w), significantly inhibited the phospholipase activity induced by the venoms of Bothrops moojeni, Bothrops atrox (11% to 31%), and Crotalus durissus terrificus (C. d. t.) (11% to 19%). The hemolytic activity induced by the venoms of B. moojeni and C. d. t. was better inhibited by the methanolic extract (inhibition between 23% and 48%). Thrombolysis induced by the venoms of B. moojeni and C. d. t. was inhibited by both extracts, with inhibition ranging from 13% to 63% for the aqueous extract, and from 12% to 92% for the methanolic one. Both extracts increased the time of coagulation induced by the venoms of B. moojeni and Lachesis muta muta in 26 and up to 68 s. These inhibitory actions were related to the following phenolic compounds present in the extract of AB: gallic acid, catechin, epigallocatechin gallate, epicatechin, syringic acid, p-coumaric acid, and quercetin. Additional studies are needed to confirm their potential use for nutraceutical purposes. PRACTICAL APPLICATION: Agro-industrial wastes are promising sources of phytochemicals for the development of products that can be used by pharmaceutical, cosmetics, and food industries. Studies report the use of the acerola bagasse extract in health improvement. However, its toxic-pharmacological characterization is still scarce. In this study, the extracts of acerola bagasse presented phenolic compounds that can modulate the activity of enzymes such as phospholipases A2 and proteases that act on the coagulant/anticoagulant and thrombotic/thrombolytic activities and the break of phospholipids, decreasing the inflammation and platelet aggregation. Although the in vivo effects of the extracts are not fully understood, this study shed light upon the possibilities of their usage.

Dynamics of Gaussian beam modeled by fractional Schrödinger equation with a variable coefficient.

In the paper, we investigate the propagation dynamics of the Gaussian beam modeled by the fractional Schrödinger equation (FSE) with a variable coefficient. In the absence of the beam's chirp, for smaller Lévy index, the Gaussian beam firstly splits into two beams, however under the action of the longitudinal periodic modulation, they exhibit a periodically oscillating behaviour. And with the increasing of the Lévy index, the splitting behaviour gradually diminishes. Until the Lévy index equals to 2, the splitting behaviour is completely replaced by a periodic diffraction behaviour. In the presence of the beam's chirp, one of the splitting beams is gradually suppressed with the increasing of the chirp, while another beam on the opposite direction becomes stronger and exhibits a periodically oscillating behaviour. Also, the oscillating amplitude and period are investigated and the results show that the former is dependent on the modulation frequency, the Lévy index and the beam's chirp, the latter depends only on the modulation frequency. Thus, the evolution of the Gaussian beam can be well manipulated to achieve the beam management in the framework of the FSE by controlling the system parameters and the chirp parameter.

In vitro antileishmanial effects of Physalis angulata root extract on Leishmania infantum

ObjectiveIn the present study, we evaluated the effects of the aqueous extract of Physalis angulata root (AEPa) on Leishmania infantum proliferation, morphology, and the driving mechanism in leishmanicidal activity and modulatory action on macrophages. MethodsL. infantum promastigotes were treated with 50 and 100 µg/mL AEPa for 72 h and then antipromastigote assay was performed by counts in a Newbauer chamber, morphological changes were analyzed by transmission electron microscopy and the mechanism of the leishmanicidal activity was detected. In addition, macrophages were infected with L. infantum and were used to evaluate anti-amastigote activity of AEPa and effects of AEPa on cytokine secretion after 72-hour treatment. ResultsTreatment with AEPa reduced the numbers of L. infantum promastigotes (50% inhibitory concentration (IC50) = 65.9 μg/mL; selectivity index (SI) = 22.1) and amastigotes (IC50 = 37.9 μg/mL; SI = 38.5) compared with the untreated control. Amphotericin B reduced 100% of the promastigote numbers after 72 h of treatment (IC50 = 0.2 μg/mL). AEPa induced several morphological changes and increased the production of reactive oxygen species and apoptotic death in promastigotes after treating for 72 h. AEPa (100 μg/mL) promoted tumor necrosis factor-α secretion in macrophages infected with L. infantum after 72 h of treatment, but did not induce an increase in this cytokine in noninfected macrophages. In addition, AEPa showed no cytotoxic effect on J774-A1 cells (50% cytotoxic concentration >1000 μg/mL). ConclusionAEPa presented antileishmanial activity against the promastigotes and amastigotes of L. infantum without macrophage cytotoxicity; these results show that natural products such as P. angulata have leishmanicidal potential and in the future may be an alternative treatment for leishmaniasis.

Abstract 534: Modulatory Effect of Nkx2.5+ Cardiomyoblast Secreted Exosomes in Cardiometabolism

It was found cardiac precursors secreted exosomes (CPC-exo) may have anti-apoptotic and anti-fibrotic actions to facilitate cardiac repair in the damaged hearts. It remains unclear the effect of CPC-exo in cardiometabolism. The aim of the study was to assess the modulatory action of CPC-exo in cardiometabolism of cardiomyopathic cardiomyocytes. Nkx2.5+ cardiomyoblasts were enzymatically isolated and were purified by FACS sorter from mouse embryonic stem cells under cardiomyogenic differentiation or transgenic mice hearts (2 weeks old) carrying GFP reporter driven by Nkx2.5-enhancer for the purification of the exosomes (mESC-Nkx2.5+exo and postnatal-Nkx2.5+exo) from the culture medium by ExoQuick-TC. The vesicle size was further measured by Nanosight. The exosomal miRNA profile was characterized by miRNA microarray. It was further compared the different effect of mESC-Nkx2.5+exo and postnatal-Nkx2.5+exo in the mitochondrial function of human cardiomyocytes derived from iPSC of left ventricle non compaction (LVNC) patients (LVNC-hiPSC-CM) by Agilent seahorse XF24 analyzer. Cell shortening was measured by Ionoptix system. It was found the defect of cardiac mitochondrial function associated with the weak cell shortening in LVNC-hiPSC-CM on day 70 after differentiation. With the treatment of mESC-Nkx2.5+exo and postnatal-Nkx2.5+exo during day 50-70, the mitochondrial function and cell shortening of LVNC-hiPSC-CM were significantly improved on day 70. The functional exosomal miRNAs were characterized in advance in this study. In conclusion, CPC-exo may exert the benefit in the improvement of cardiometabolism in cardiomyopathic cardiomyocytes.

Some properties of $$LUC({\mathcal X},{\mathcal G})^*$$ L U C ( X , G ) ∗ as a banach left $$LUC({\mathcal G})^*$$ L U C ( G ) ∗ -module

Associated with a locally compact group $$\mathcal G$$ and a $$\mathcal G$$ -space $$\mathcal X$$ there is a Banach subspace $$LUC({\mathcal X},{\mathcal G})$$ of $$C_b({\mathcal X})$$ , which has been introduced and studied by Chu and Lau (Math Z 268:649–673, 2011). In this paper, we study some properties of the first dual space of $$LUC({\mathcal X},{\mathcal G})$$ . In particular, we introduce a left action of $$LUC({\mathcal G})^*$$ on $$LUC({\mathcal X},{\mathcal G})^*$$ to make it a Banach left module and then we investigate the Banach subalgebra $${{\mathfrak {Z}}({\mathcal X},{\mathcal G})}$$ of $$LUC({\mathcal G})^*$$ , as the topological centre related to this module action, which contains $$M({\mathcal G})$$ as a closed subalgebra. Also, we show that the faithfulness of this module action is related to the properties of the action of $$\mathcal G$$ on $$\mathcal X$$ and we prove an analogue of the main result of Lau (Math Proc Cambridge Philos Soc 99:273–283, 1986) for $${\mathcal G}$$ -spaces. Sufficient and/or necessary conditions for the equality $${{\mathfrak {Z}}({\mathcal X},{\mathcal G})}=M({\mathcal G})$$ or $$LUC({\mathcal G})^*$$ are given. Finally, we apply our results to some special cases of $$\mathcal G$$ and $$\mathcal X$$ for obtaining various examples whose topological centres $${{\mathfrak {Z}}({\mathcal X},{\mathcal G})}$$ are $$M({\mathcal G})$$ , $$LUC({\mathcal G})^*$$ or neither of them.

TAG synthesis and storage under osmotic stress. A requirement for preserving membrane homeostasis in renal cells

Hyperosmolarity is a controversial signal for renal cells. It can induce cell stress or differentiation and both require an active lipid metabolism. We showed that hyperosmolarity upregulates phospholipid (PL) de novo synthesis in renal cells. PL synthesis requires fatty acids (FA), usually stored as triglycerides (TAG). PL and TAG de novo synthesis utilize the same initial biosynthetic route: sn-glycerol 3P (G3P) → phosphatidic acid (PA) → diacylglycerol (DAG). In the present work, we evaluate how such pathway contributes to PL and TAG synthesis in renal cells subjected to hyperosmolarity. Our results show an increase in PA and DAG formation under hyperosmotic conditions; augmented DAG production, due to lipin enzyme activity, lead to the increase of both TAG and PL. However, at early stages (24 and 48 h), most of the de novo synthesized DAG was directed to PL synthesis; longer treatments downregulated PL synthesis and the DAG formed was mainly driven to TAG synthesis. Hyperosmolarity induced ACC and FASN transcription which mediated FA de novo synthesis. New FA molecules were stored in TAG. Silencing experiments revealed that hyperosmotic-induction of lipin-1 and -2 was mediated by SREBP1. Interestingly, SREBP1 knockdown also dropped SREBP2, indicating a modulatory action between both isoforms. Impairing SREBP activity leads to a decline in TAG levels but not PL. Membrane homeostasis is maintained through the adequate PL synthesis and renewal and constitute a protective mechanism against hyperosmolarity. The present data reveal the relevance of TAG synthesis and storage for PL synthesis in renal cells.

Concentration-dependent protein loading of extracellular vesicles released by Histoplasma capsulatum after antibody treatment and its modulatory action upon macrophages

Diverse pathogenic fungi secrete extracellular vesicles (EV) that contain macromolecules, including virulence factors that can modulate the host immune response. We recently demonstrated that the binding of monoclonal antibodies (mAb) modulates how Histoplasma capsulatum load and releases its extracellular vesicles (EV). In the present paper, we addressed a concentration-dependent impact on the fungus’ EV loading and release with different mAb, as well as the pathophysiological role of these EV during the host-pathogen interaction. We found that the mAbs differentially regulate EV content in concentration-dependent and independent manners. Enzymatic assays demonstrated that laccase activity in EV from H. capsulatum opsonized with 6B7 was reduced, but urease activity was not altered. The uptake of H. capsulatum by macrophages pre-treated with EV, presented an antibody concentration-dependent phenotype. The intracellular killing of yeast cells was potently inhibited in macrophages pre-treated with EV from 7B6 (non-protective) mAb-opsonized H. capsulatum and this inhibition was associated with a decrease in the reactive-oxygen species generated by these macrophages. In summary, our findings show that opsonization quantitatively and qualitatively modifies H. capsulatum EV load and secretion leading to distinct effects on the host’s immune effector mechanisms, supporting the hypothesis that EV sorting and secretion are dynamic mechanisms for a fine-tuned response by fungal cells.