Stochastic dynamics of Francisella tularensis infection and replication

We study the pathogenesis of Francisella tularensis infection with an experimental mouse model, agent-based computation and mathematical analysis. Following inhalational exposure to Francisella tularensis SCHU S4, a small initial number of bacteria enter lung host cells and proliferate inside them, eventually destroying the host cell and releasing numerous copies that infect other cells. Our analysis of disease progression is based on a stochastic model of a population of infectious agents inside one host cell, extending the birth-and-death process by the occurrence of catastrophes: cell rupture events that affect all bacteria in a cell simultaneously. Closed expressions are obtained for the survival function of an infected cell, the number of bacteria released as a function of time after infection, and the total bacterial load. We compare our mathematical analysis with the results of agent-based computation and, making use of approximate Bayesian statistical inference, with experimental measurements carried out after murine aerosol infection with the virulent SCHU S4 strain of the bacterium Francisella tularensis, that infects alveolar macrophages. The posterior distribution of the rate of replication of intracellular bacteria is consistent with the estimate that the time between rounds of bacterial division is less than 6 hours in vivo

Quantifying the phosphorylation timescales of receptor–ligand complexes: a Markovian matrix-analytic approach

Cells interact with the extracellular environment by means of receptor molecules on their surface. Receptors can bind different ligands, leading to the formation of receptor–ligand complexes. For a subset of receptors, called receptor tyrosine kinases, binding to ligand enables sequential phosphorylation of intra-cellular residues, which initiates a signalling cascade that regulates cellular function and fate. Most mathematical modelling approaches employed to analyse receptor signalling are deterministic, especially when studying scenarios of high ligand concentration or large receptor numbers. There exist, however, biological scenarios where low copy numbers of ligands and/or receptors need to be considered, or where signalling by a few bound receptor–ligand complexes is enough to initiate a cellular response. Under these conditions stochastic approaches are appropriate, and in fact, different attempts have been made in the literature to measure the timescales of receptor signalling initiation in receptor–ligand systems. However, these approaches have made use of numerical simulations or approximations, such as moment-closure techniques. In this paper, we study, from an analytical perspective, the stochastic times to reach a given signalling threshold for two receptor–ligand models. We identify this time as an extinction time for a conveniently defined auxiliary absorbing continuous time Markov process, since receptor–ligand association/dissociation events can be analysed in terms of quasi-birth-and-death processes. We implement algorithmic techniques to compute the different order moments of this time, as well as the steady-state probability distribution of the system. A novel feature of the approach introduced here is that it allows one to quantify the role played by each kinetic rate in the timescales of signal initiation, and in the steady-state probability distribution of the system. Finally, we illustrate our approach by carrying out numerical studies for the vascular endothelial growth factor and one of its receptors, the vascular endothelial growth factor receptor of human endothelial cells

An Exploratory Study of Healing Circles as a Strategy to Facilitate Resilience in an Undocumented Community

Within the United States, the COVID-19 pandemic highlighted critical inequalities affecting undocumented communities and resulting in particularly heightened stress for members of these communities. In addition to the stress associated with COVID-19, immigrants in the United States were more than ever subjected to a hostile antiimmigrant climate under Trump’s administration. Given this compounded stress, the impact of the pandemic on mental health is likely to be disproportionately experienced by undocumented immigrants. In response, a group of psychologists partnered with a leading immigrant rights advocacy organization and formed a reciprocal collaboration to support undocumented communities. A major focus of the collaboration is to foster learning, supporting members of the immigrant community to contribute to their own well-being and others in the community. Accordingly, the collaborative developed and delivered a web-based mental health education session to the immigrant community and to practitioners serving this population. The session presented the use of healing circles as a strength-based approach to building resilience and also sought feedback regarding specific features of healing circles that can enhance their effectiveness in managing distress. Survey data and qualitative findings from this study show that those who participated in the web-based program perceived the session as validating and informative. Findings also underscored the need for creating safe spaces for community members to be vulnerable about their lived experiences while promoting ownership of their narratives. We discuss practical implications pertaining to the development and facilitation of social support groups for immigrants led by nonspecialist community members trained for this role. Impact Statement We describe a reciprocal collaboration between psychologists and an immigrant-led advocacy organization for the purposes of supporting undocumented immigrants in tailoring culturally congruent therapeutic approaches for fostering resilience as they face multiple stressors due to interlocking crises, such as the COVID-19 pandemic and antiimmigrant policies. The collaboration led to the development and delivery of a web-based session that provided immigrant community members and practitioners with recommendations for facilitating healing circles as a strength-based and culturally responsive approach to fostering peer-led social support during stressful times. Findings highlight the need for creating such safe spaces for community members to be vulnerable about their lived experiences and feel validated

Role of genetic heterogeneity in determining the epidemiological severity of H1N1 influenza

Genetic differences contribute to variations in the immune response mounted by different individuals to a pathogen. Such differential response can influence the spread of infectious disease, indicating why such diseases impact some populations more than others. Here, we study the impact of population-level genetic heterogeneity on the epidemic spread of different strains of H1N1 influenza. For a population with known HLA class-I allele frequency and for a given H1N1 viral strain, we classify individuals into sub-populations according to their level of susceptibility to infection. Our core hypothesis is that the susceptibility of a given individual to a disease such as H1N1 influenza is inversely proportional to the number of high affinity viral epitopes the individual can present. This number can be extracted from the HLA genetic profile of the individual. We use ethnicity-specific HLA class-I allele frequency data, together with genome sequences of various H1N1 viral strains, to obtain susceptibility sub-populations for 61 ethnicities and 81 viral strains isolated in 2009, as well as 85 strains isolated in other years. We incorporate these data into a multi-compartment SIR model to analyse the epidemic dynamics for these (ethnicity, viral strain) epidemic pairs. Our results show that HLA allele profiles which lead to a large spread in individual susceptibility values can act as a protective barrier against the spread of influenza. We predict that populations skewed such that a small number of highly susceptible individuals coexist with a large number of less susceptible ones, should exhibit smaller outbreaks than populations with the same average susceptibility but distributed more uniformly across individuals. Our model tracks some well-known qualitative trends of influenza spread worldwide, suggesting that HLA genetic diversity plays a crucial role in determining the spreading potential of different influenza viral strains across populations

Correlación de la respuesta a antígenos de Mycobacterium tuberculosis y la prueba cutánea de tuberculina en pacientes con artritis reumatoide

Introduction. Rheumatoid arthritis patients under treatment with anti-TNF-α are at a high risk of developing active tuberculosis, and therefore, screening for latent tuberculosis infection is recommended before anti-TNF-α therapy.Objective. To compare the tuberculin test and IFNγ production induced by culture filtrate proteins (CFPs) and Mycobacterium tuberculosis-specific CFP-10 antigens in rheumatoid arthritis patients.Materials and methods. An analytic transversal study was conducted in rheumatoid arthritis patients treated at Hospital Universitario San Vicente Fundación between January and December 2007. IFNγ production in response to CFPs and CFP-10 was measured in the supernatants of whole blood cultures and evaluated for correlations with tuberculin reactivity. The degree of concordance between both tests was also established.Results. Forty-five patients were included, of which 14 (31.1%) had a tuberculin reaction of ≥10 mm of induration, 9 (20%) produced IFNγ in response to CFP-10, and 7 were positive for both tests. The correlation between tests was r=0.53 (IC 95%:0.28-0.72), and the global concordance between tests was 80%, with a Kappa coefficient of 0.48 (IC95%:0.20-0.76).Conclusions. Only two tuberculin (-)/CFP-10+ “anergic” patients were observed. By contrast, six tuberculin +/CFP-10(-) “tuberculin false-positive” patients were observed. These data suggest that the tuberculin test is not an appropriate tool for determining the need for tuberculosis prophylaxis. doi: http://dx.doi.org/10.7705/biomedica.v33i2.694  Introducción. Los pacientes con artritis reumatoide bajo tratamiento con anti-TNFα están en alto riesgo de desarrollar tuberculosis activa, por lo cual se recomienda hacer la tamización para infección latente de tuberculosis, antes de iniciar el tratamiento.Objetivo. Comparar la prueba de tuberculina y la producción de IFNγ inducida por antígenos CFP (Culture Filtrate Protein) y antígenos específicos de Mycobacterium tuberculosis (CFP-10) para el diagnóstico de infección latente de tuberculosis en pacientes con artritis reumatoide.Materiales y métodos. Se llevó a cabo un estudio transversal analítico en pacientes con artritis reumatoide atendidos en el Hospital Universitario San Vicente Fundación, entre enero y diciembrede 2007, a los cuales se les determinó la producción de IFNγ en respuesta a CFP y CFP-10 en sobrenadantes de cultivos de sangre total, y se correlacionó con la reacción en la prueba de tuberculina. Además, se estableció el grado de concordancia entre ambas pruebas.Resultados. Se incluyeron 45 pacientes, de los cuales, 14 (31,1 %) tuvieron un diámetro de induración≥10 mm (tuberculina positiva), nueve (20 %) produjeron IFNγ en respuesta a CFP-10, y siete fueron positivos para ambas pruebas. La correlación entre las pruebas fue de r=0,53 (IC95%: 0,28-0,72) y la concordancia global entre pruebas fue de 80 %, con un coeficiente kappa de 0,48 (IC95%: 0,20-0,76).Conclusiones. Solo se observaron dos pacientes con tuberculina positiva y CFP-10 positivo “anérgicos”y se encontraron seis pacientes con tuberculina positiva y CFP-10 negativa “falsos positivos paratuberculina”, lo cual sugiere que la prueba de la tuberculina no es la más adecuada para indicar profilaxispara tuberculosis. doi: http://dx.doi.org/10.7705/biomedica.v33i2.694

A comprehensive RNA-Seq-based gene expression atlas of the summer squash (Cucurbita pepo) provides insights into fruit morphology and ripening mechanisms

Background: Summer squash (Cucurbita pepo: Cucurbitaceae) are a popular horticultural crop for which there is insufficient genomic and transcriptomic information. Gene expression atlases are crucial for the identification of genes expressed in different tissues at various plant developmental stages. Here, we present the first comprehensive gene expression atlas for a summer squash cultivar, including transcripts obtained from seeds, shoots, leaf stem, young and developed leaves, male and female flowers, fruits of seven developmental stages, as well as primary and lateral roots. Results: In total, 27,868 genes and 2352 novel transcripts were annotated from these 16 tissues, with over 18,000 genes common to all tissue groups. Of these, 3812 were identified as housekeeping genes, half of which assigned to known gene ontologies. Flowers, seeds, and young fruits had the largest number of specific genes, whilst intermediate-age fruits the fewest. There also were genes that were differentially expressed in the various tissues, the male flower being the tissue with the most differentially expressed genes in pair-wise comparisons with the remaining tissues, and the leaf stem the least. The largest expression change during fruit development was early on, from female flower to fruit two days after pollination. A weighted correlation network analysis performed on the global gene expression dataset assigned 25,413 genes to 24 coexpression groups, and some of these groups exhibited strong tissue specificity. Conclusions: These findings enrich our understanding about the transcriptomic events associated with summer squash development and ripening. This comprehensive gene expression atlas is expected not only to provide a global view of gene expression patterns in all major tissues in C. pepo but to also serve as a valuable resource for functional genomics and gene discovery in Cucurbitaceae

Co-ocurrencia de uranio, vanadio y molibdeno en acuíferos chaco-pampeanos (Argentina) : Fuentes, movilidad y procesos de concentración en diversas cuencas

Concentraciones anómalas de uranio (U), vanadio (V) y molibdeno (Mo), asociadas con arsénico en aguas subterráneas de la Llanura Chaco-Pampeana generan toxicidad que limitan su utilización e ingesta. Se muestran resúmenes estadísticos para las cuencas del río Salí y de Burruyacú (Tucumán), la llanura centro-norte de Santa Fe, las llanuras sudoriental de Córdoba, norte de La Pampa y sudeste de Buenos Aires.En acuíferos someros de la cuenca del río Salí, los máximos de U, V y Mo son, respectivamente: 125, 300 y 727 μgL-1; (medianas: 14,2, 77,3 y 10,9 μgL-1, respectivamente). En sedimentos (mg kg-1): 12,4, 99,0 y <2, respectivamente (medianas: 3,88, 85,0 y <2, respectivamente).Estas concentraciones están relacionadas con disolución de vidrio volcánico, lixiviación de sedimentos loésicos, sorción sobre superficie de óxidos y oxi-hidróxidos de Al, Fe y Mn, y desorción a valores de pH más altos, con formación de iones complejos estables, con alta movilidad.Anomalous concentrations of uranium (U), vanadium (V) and molybdenum (Mo), associated to ar senic (As) in groundwater from the Chaco-Pampean Plain causes toxicity, therefore utilization and consumption must be restricted. Statistical summaries from the Salí river and Burruyacú basins (Tucumán), the northern-central plain of Santa Fe, and the southeastern plains of Córdoba, northern La Pampa and southeastern Buenos Aires were shown. In shallow aquifers from the Salí river basin maxima concentrations of U, V and Mo are respectively: 125 μgL-1, 300 μgL-1, 727 μgL-1 (medians: 14.2, 77.3 and 10.9 μgL-1 respectively). In sediments (mg kg-1): 12.4, 99.0 and &lt;2 (medians: 3.88, 85.0 and &lt;2). Such concentrations are related to the volcanic-glass dissolution and leaching of loess-like sediments, sorption onto surface from Al-, Fe- and Mn oxides and oxihydroxides, and desorption at higher pH values and formation of stable complex-ions with high mobility.Universidad Nacional de La Plat

Ultracool dwarfs candidates based on six years of the Dark Energy Survey data

We present a sample of 19,583 ultracool dwarf candidates brighter than z $\leq 23$ selected from the Dark Energy Survey DR2 coadd data matched to VHS DR6, VIKING DR5 and AllWISE covering $\sim$ 4,800 $deg^2$. The ultracool candidates were first pre-selected based on their (i-z), (z-Y), and (Y-J) colours. They were further classified using a method that compares their optical, near-infrared and mid-infrared colours against templates of M, L and T dwarfs. 14,099 objects are presented as new L and T candidates and the remaining objects are from the literature, including 5,342 candidates from our previous work. Using this new and deeper sample of ultracool dwarf candidates we also present: 20 new candidate members to nearby young moving groups (YMG) and associations, variable candidate sources and four new wide binary systems composed of two ultracool dwarfs. Finally, we also show the spectra of twelve new ultracool dwarfs discovered by our group and presented here for the first time. These spectroscopically confirmed objects are a sanity check of our selection of ultracool dwarfs and photometric classification method.Comment: 18 pages, 10 figures, 7 tables. Accepted for publication in MNRA

Ultracool dwarfs candidates based on 6 yr of the Dark Energy Survey data

We present a sample of 19 583 ultracool dwarf candidates brighter than z ≤23 selected from the Dark Energy Survey DR2 coadd data matched to VHS DR6, VIKING DR5, and AllWISE covering ∼ 480 deg2. The ultracool candidates were first pre-selected based on their (i–z), (z–Y), and (Y–J) colours. They were further classified using a method that compares their optical, near-infrared, and mid-infrared colours against templates of M, L, and T dwarfs. 14 099 objects are presented as new L and T candidates and the remaining objects are from the literature, including 5342 candidates from our previous work. Using this new and deeper sample of ultracool dwarf candidates we also present: 20 new candidate members to nearby young moving groups and associations, variable candidate sources and four new wide binary systems composed of two ultracool dwarfs. Finally, we also show the spectra of 12 new ultracool dwarfs discovered by our group and presented here for the first time. These spectroscopically confirmed objects are a sanity check of our selection of ultracool dwarfs and photometric classification method