Sporotrichosis is a subcutaneous mycosis caused by pathogenic species of the Sporothrix genus. A new emerging species, Sporothrix brasiliensis, is related to cat-transmitted sporotrichosis and has ...severe clinical manifestations. The cell wall of pathogenic fungi is a unique structure and impacts directly on the host immune response. We reveal and compare the cell wall structures of Sporothrix schenckii and S. brasiliensis using high-pressure freezing electron microscopy to study the cell wall organization of both species. To analyze the components of the cell wall, we also used infrared and 13C and 1H NMR spectroscopy and the sugar composition was determined by quantitative high-performance anion-exchange chromatography. Our ultrastructural data revealed a bi-layered cell wall structure for both species, including an external microfibrillar layer and an inner electron-dense layer. The inner and outer layers of the S. brasiliensis cell wall were thicker than those of S. schenckii, correlating with an increase in the chitin and rhamnose contents. Moreover, the outer microfibrillar layer of the S. brasiliensis cell wall had longer microfibrils interconnecting yeast cells. Distinct from those of other dimorphic fungi, the cell wall of Sporothrix spp. lacked α-glucan component. Interestingly, glycogen α-particles were identified in the cytoplasm close to the cell wall and the plasma membrane. The cell wall structure as well as the presence of glycogen α-particles varied over time during cell culture. The structural differences observed in the cell wall of these Sporothrix species seemed to impact its uptake by monocyte-derived human macrophages. The data presented here show a unique cell wall structure of S. brasiliensis and S. schenckii during the yeast parasitic phase. A new cell wall model for Sporothrix spp. is therefore proposed that suggests that these fungi molt sheets of intact cell wall layers. This observation may have significant effects on localized and disseminated immunopathology.
is a human opportunist pathogen that can grow as yeast, pseudohyphae, or true hyphae
and
, depending on environmental conditions. Reversible cellular morphogenesis is an important virulence factor ...that facilitates invasion of host tissues, escape from phagocytes, and dissemination in the blood stream. The innate immune system is the first line of defense against
infections and is influenced by recognition of wall components that vary in composition in different morphological forms. However, the relationship between cellular morphogenesis and immune recognition of this fungus is not fully understood. We therefore studied various vegetative cell types of
, singly and in combination, to assess the consequences of cellular morphogenesis on selected immune cytokine outputs from human monocytes. Hyphae stimulated proportionally lower levels of certain cytokines from monocytes per unit of cell surface area than yeast cells, but did not suppress cytokine response when copresented with yeast cells. Pseudohyphal cells induced intermediate cytokine responses. Yeast monomorphic mutants had elevated cytokine responses under conditions that otherwise supported filamentous growth and mutants of yeast and hyphal cells that were defective in cell wall mannosylation or lacking certain hypha-specific cell wall proteins could variably unmask or deplete the surface of immunostimulatory ligands. These observations underline the critical importance of
morphology and morphology-associated changes in the cell wall composition that affect both immune recognition and pathogenesis.
The ball-burnishing process involves a surface plastic deformation that improves the physical-mechanical properties of manufactured parts. In this work, was used to study the influence of the main ...parameters of the ball-burnishing process on features such as mean surface roughness and hardness of cylindrical AISI 1045 steel samples. The experimental stage was based on a 33 factorial design and the Response Surface Methodology. An equation was proposed to model the mean roughness in the studied experimental region. Moreover, the polarization technique (Tafel) and electrochemical impedance spectroscopy (EIS) were used to evaluate the burnishing process effect on corrosion resistance of a sample machined with the optimal burnishing parameters obtained herein. Finally, burnishing process effect on the phase change was also evaluated by using X-ray diffraction. As a result, the factor that showed higher influence was the burnishing force for both features, roughness and hardness. The data shows that it is possible to reduce the surface roughness from 3.51 μm to 0.61 μm and to increase the hardness from 202 HB to 236 HB using ball-burnishing process, and to improve the corrosion resistance in AISI-1045 steel.
•Surface mean roughness enhanced 83% on optimal burnished AISI 1045 steel sample.•Hardness on AISI 1045 steel samples improved 14% with optimal burnishing parameters.•A prediction model is presented for the surface mean roughness with an error of 8%.•Tafel and EIS indicate an increase on corrosion resistance in burnished samples.•X-ray diffraction suggests an increase of d-spacing due to burnishing process.
The β-glucan receptor Dectin-1 is a member of the C-type lectin family and functions as an innate pattern recognition receptor in antifungal immunity. In both mouse and man, Dectin-1 has been found ...to play an essential role in controlling infections with Candida albicans, a normally commensal fungus in man which can cause superficial mucocutaneous infections as well as life-threatening invasive diseases. Here, using in vivo models of infection, we show that the requirement for Dectin-1 in the control of systemic Candida albicans infections is fungal strain-specific; a phenotype that only becomes apparent during infection and cannot be recapitulated in vitro. Transcript analysis revealed that this differential requirement for Dectin-1 is due to variable adaptation of C. albicans strains in vivo, and that this results in substantial differences in the composition and nature of their cell walls. In particular, we established that differences in the levels of cell-wall chitin influence the role of Dectin-1, and that these effects can be modulated by antifungal drug treatment. Our results therefore provide substantial new insights into the interaction between C. albicans and the immune system and have significant implications for our understanding of susceptibility and treatment of human infections with this pathogen.
Chitin is a skeletal cell wall polysaccharide of the inner cell wall of fungal pathogens. As yet, little about its role during fungus-host immune cell interactions is known. We show here that ...ultrapurified chitin from Candida albicans cell walls did not stimulate cytokine production directly but blocked the recognition of C. albicans by human peripheral blood mononuclear cells (PBMCs) and murine macrophages, leading to significant reductions in cytokine production. Chitin did not affect the induction of cytokines stimulated by bacterial cells or lipopolysaccharide (LPS), indicating that blocking was not due to steric masking of specific receptors. Toll-like receptor 2 (TLR2), TLR4, and Mincle (the macrophage-inducible C-type lectin) were not required for interactions with chitin. Dectin-1 was required for immune blocking but did not bind chitin directly. Cytokine stimulation was significantly reduced upon stimulation of PBMCs with heat-killed chitin-deficient C. albicans cells but not with live cells. Therefore, chitin is normally not exposed to cells of the innate immune system but is capable of influencing immune recognition by blocking dectin-1-mediated engagement with fungal cell walls.
La carrera de Ingeniería Industrial de la Universidad Hispanoamericana (UH), luego de obtener su acreditación con el SINAES en mayo del 2022 busca continuar mejorando su oferta y mediante la ...comparación con otros programas académicos homólogos y que poseen la acreditación del Acuerdo de Washington o su equivalente mediante acuerdos de reconocimiento mutuo con otros estándares del mercado; para usar las brechas detectadas y solventarlas. En esta oportunidad la comparación se realiza con dos universidades del TOP5 en el ranking QS del año 2022.
Abstract
Background
Hispanics in the United States are disproportionately affected by the novel coronavirus (COVID-19). While social distancing and quarantining are effective methods to reduce its ...spread, Hispanics, who are more likely to be essential workers and live in multigenerational homes than non-Hispanics, may face challenges that limit their ability to carry out these preventative efforts. We elicited the experiences of Hispanic adults with social distancing and self-quarantining during the COVID-19 pandemic in New York.
Methods
In this qualitative study, Hispanic adults receiving care at a federally qualified community health center in East Harlem, New York, were recruited for remote one-on-one semi-structured interviews from 5/15/2020 to 11/17/2020. Interviews were conducted by a bilingual interviewer in Spanish or English, using a semi-structured topic guide informed by the Health Belief Model. Audio-recordings were professionally transcribed. We used thematic analysis to iteratively code the data. Each transcript was independently coded by two research team members, then reconciled by a third. Major themes and subthemes were identified.
Results
Among 20 participants, four major themes emerged; Hispanics were: (1) fearful of contracting and transmitting COVID-19, (2) engaging in practices to reduce transmission of COVID-19, (3) experiencing barriers to social distancing and quarantining, and (4) facing an enduring psychological and physical toll from COVID-19.
Conclusions
Despite understanding the risks for contracting COVID-19 and taking appropriate precautions, Hispanics faced numerous challenges to social distancing and quarantining, such as living in crowded, multi-generational households, working as essential workers, and providing unpaid care to family members. Such challenges took a toll on their physical, emotional, and financial well-being. Our findings suggest that a tailored approach to public health messaging and interventions for pandemic planning are warranted among members of this community. Further research is needed to understand and mitigate the long term physical and psychological consequences of the pandemic among Hispanics.
Northwestern Colombia is located at a convergent plate boundary between the Caribbean plate and the North Andean Block; however, no megathrust earthquakes have been reported during last 500 years. In ...order to evaluate seismic potential in this area, we analyze GPS data during 2007–2018 from GeoRED – the nationwide GPS array in Colombia – to obtain interseismic 3-dimensional velocities. GPS velocity data indicate the northern part of the North Andean Block is differentiated as another block and we name it Macondo Block. The velocity data are then inverted to estimate interplate coupling on the subducting Caribbean plate interface. The result shows an isolated, fully locked patch south of the city of Cartagena extending from 9.0 to 20 km in depth on the subduction interface with an area of ~11,000 km2. The estimated locked patch implies a potential of M-8 class earthquake with an average recurrence time of ~600 years, which is consistent with the absence of such an event in the available historical record. As another possibility, the observed surface deformation may be accommodated inelastically. A comparison of geological and geodetic strain rates in the convergence direction shows that the geological one is smaller by one or two orders of magnitude and does not support such an interpretation though the estimate itself still has a large uncertainty. For improving the evaluation of earthquake/tsunami potential, it is essential to conduct a careful geological investigation to identify recent evidence of crustal shortening or paleotsunami along northwestern Colombia.
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•Newly defined “Macondo block” in the northern North Andean Block.•Slow subduction of the Caribbean plate in northwestern Colombia.•Full interplate coupling on the Caribbean subduction near the city of Cartagena.•Possibility of a M8.0 earthquake with a recurrence time of 600 years is suggested.•Order of magnitude discrepancy between geodetic and geologic strain rate in the San Jacinto Fold Belt.
Recognition of microbial components by germ-line encoded pattern recognition receptors (PRR) initiates immune responses to infectious agents. We and others have proposed that pairs or sets of PRR ...mediate host immunity. One such pair comprises the fungal β-glucan receptor, Dectin-1, which collaborates through an undefined mechanism with Toll-like receptor 2 (TLR2) to induce optimal cytokine responses in macrophages. We show here that Dectin-1 signaling through the spleen tyrosine kinase (Syk) pathway is required for this collaboration, which can also occur with TLR4, 5, 7 and 9. Deficiency of either Syk or the TLR adaptor MyD88 abolished collaborative responses, which include TNF, MIP-1α and MIP-2 production, and which are comparable to the previously described synergy between TLR2 and TLR4. Collaboration of the Syk and TLR/MyD88 pathways results in sustained degradation of the inhibitor of kB (IkB), enhancing NFkB nuclear translocation. These findings establish the first example of Syk- and MyD88-coupled PRR collaboration, further supporting the concept that paired receptors collaborate to control infectious agents.
Motivated behavior can be characterized by behavioral activation and high work output. Moreover, people with depression and other disorders show effort-related motivational symptoms, such as anergia, ...psychomotor retardation, and fatigue. Effort-based decision making is studied using tasks offering choices between high effort options leading to highly valued reinforcers vs low effort/low reward options, and such tasks could be useful as animal models of motivational symptoms. In the present studies the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine (TBZ) were investigated. TBZ blocks vesicular storage and also produces depressive symptoms in humans. Moreover, TBZ alters effort-based choice in rats, biasing animals toward low effort alternatives. The present studies investigated the ability of acute administration of various monoamine uptake inhibitors to reverse the effects of TBZ. Effort-related effects of TBZ were attenuated by the catecholamine uptake inhibitor and antidepressant bupropion, and this effect of bupropion was reversed by either D1 or D2 family antagonism. The effort-related effects of TBZ were also attenuated by the selective dopamine uptake blocker GBR12909. The 5-HT uptake inhibitor fluoxetine and the norepinephrine uptake inhibitor desipramine failed to reverse the effects of TBZ, and higher doses of these drugs, given alone or in combination with TBZ, led to further behavioral impairments. These results indicate that drugs acting on dopamine transmission are relatively effective at reversing the effort-related effects of TBZ, and are consistent with the hypothesis that drugs that enhance dopamine transmission may be effective at treating effort-related psychiatric symptoms in humans.
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