Organoids as host models for infection biology – a review of methods

Infectious diseases are a major threat worldwide. With the alarming rise of antimicrobial resistance and emergence of new potential pathogens, a better understanding of the infection process is urgently needed. Over the last century, the development of in vitro and in vivo models has led to remarkable contributions to the current knowledge in the field of infection biology. However, applying recent advances in organoid culture technology to research infectious diseases is now taking the field to a higher level of complexity. Here, we describe the current methods available for the study of infectious diseases using organoid cultures.We thank Rike Zietlow for editing of the manuscript. This work was supported by the European Union’s Horizon 2020 Research and Innovation program under grant agreement No. 857491 to A.S.O., M.Sa., and S.B.; BMBF grant NUM-COVID 19 Organo-Strat 01KX2021 to S.B.; and FCT, grant CEEC, to M.Sa

THE TEACHING OF THE ENGLISH LANGUAGE TO DEAF STUDENTS IN REMOTE EDUCATION: CHALLENGES AND INCLUSION

Undergraduate final work entitled THE TEACHING OF THE ENGLISH LANGUAGE TO DEAF STUDENTS IN REMOTE EDUCATION: challenges and inclusion, is the result of undergraduate research linked to the English Language Course at the Universidade Federal do Pará. The research aimed to investigate the challenges faced by English language teachers in teaching deaf students during remote education, describing what institutional support EL teachers had during the pandemic, the research methodology involved bibliographic research bringing as theoretical segments the Declaration of Salamanca (1994), the Lei da Libras (2002), Skliar (1998), Santos (2020), Spasiani (2018), Tavares and Oliveira (2022), and others, and field research, of the case study type with an approach qualitative, having EL teachers as research subject, from BBS and Leandro Lobão schools, in Bragança-Pará, to collect data an online questionnaire was used. The results showed that the lack of institutional support to assist and train teachers to teach these students in the pandemic were the main challenges encountered.

Measurement of Galactic Logarithmic Spiral Arm Pitch Angle Using Two-Dimensional Fast Fourier Transform Decomposition

A logarithmic spiral is a prominent feature appearing in a majority of observed galaxies. This feature has long been associated with the traditional Hubble classification scheme, but historical quotes of pitch angle of spiral galaxies have been almost exclusively qualitative. We have developed a methodology, utilizing two-dimensional fast Fourier transformations of images of spiral galaxies, in order to isolate and measure the pitch angles of their spiral arms. Our technique provides a quantitative way to measure this morphological feature. This will allow comparison of spiral galaxy pitch angle to other galactic parameters and test spiral arm genesis theories. In this work, we detail our image processing and analysis of spiral galaxy images and discuss the robustness of our analysis techniques.Comment: 23 pages, 22 figures, and 3 Tables; published in ApJS 199, 33 http://iopscience.iop.org/0067-0049/199/2/33/; software available for download at http://dafix.uark.edu/~ages/downloads.html and http://astro.host.ualr.edu/2DFFT

Differential production of type I IFN determines the reciprocal levels of IL-10 and proinflammatory cytokines produced by C57BL/6 and BALB/c macrophages

Pattern recognition receptors detect microbial products and induce cytokines, which shape the immunological response. IL-12, TNF-alpha, and IL-1 beta are proinflammatory cytokines, which are essential for resistance against infection, but when produced at high levels they may contribute to immunopathology. In contrast, IL-10 is an immunosuppressive cytokine, which dampens proinflammatory responses, but it can also lead to defective pathogen clearance. The regulation of these cytokines is therefore central to the generation of an effective but balanced immune response. In this study, we show that macrophages derived from C57BL/6 mice produce low levels of IL-12, TNF-alpha, and IL-1 beta, but high levels of IL-10, in response to TLR4 and TLR2 ligands LPS and Pam3CSK4, as well as Burkholderia pseudomallei, a Gram-negative bacterium that activates TLR2/4. In contrast, macrophages derived from BALB/c mice show a reciprocal pattern of cytokine production. Differential production of IL-10 in B. pseudomallei and LPS-stimulated C57BL/6 and BALB/c macrophages was due to a type I IFN and ERK1/2-dependent, but IL-27-independent, mechanism. Enhanced type I IFN expression in LPS-stimulated C57BL/6 macrophages was accompanied by increased STAT1 and IFN regulatory factor 3 activation. Furthermore, type I IFN contributed to differential IL-1 beta and IL-12 production in B. pseudomallei and LPS-stimulated C57BL/6 and BALB/c macrophages via both IL-10-dependent and -independent mechanisms. These findings highlight key pathways responsible for the regulation of pro- and anti-inflammatory cytokines in macrophages and reveal how they may differ according to the genetic background of the host.his work was supported by The Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001126), the U.K. Medical Research Council (FC001126), and the Wellcome Trust (FC001126) since April 1, 2015 and before that by U.K. Medical Research Council Grant MRC U117565642 and also by European Research Council Grant 294682-TB-PATH (Crick 10127). A.H. was additionally funded by a U.K. Medical Research Council Centenary Award. M.S. was funded by Fundação para a Ciência e Tecnologia, Portugal Grant FCT-ANR/BIM-MEC/ 0007/2013. M.S. is an associate Fundação para a Ciência e Tecnologia, Portugal investigator.info:eu-repo/semantics/publishedVersio

Extensive Copy-Number Variation of Young Genes across Stickleback Populations

MM received funding from the Max Planck innovation funds for this project. PGDF was supported by a Marie Curie European Reintegration Grant (proposal nr 270891). CE was supported by German Science Foundation grants (DFG, EI 841/4-1 and EI 841/6-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

An environmental evaluation of food waste downstream management options: a hybrid LCA approach

Food waste treatment methods have been typically analysed using current energy generation conditions. To correctly evaluate treatment methods, they must be compared under existing and potential decarbonisation scenarios. This paper holistically quantifies the environmental impacts of three food waste downstream management options—incineration, composting, and anaerobic digestion (AD). Methods The assessment was carried out using a novel hybrid input–output-based life cycle assessment method (LCA), for 2014, and in a future decarbonised economy. The method introduces expanded system boundaries which reduced the level of incompleteness, a previous limitation of process-based LCA. Results Using the 2014 UK energy mix, composting achieved the best score for seven of 14 environmental impacts, while AD scored second best for ten. Incineration had the highest environmental burdens in six impacts. Uncertainties in the LCA data made it difficult determine best treatment option. There was significant environmental impact from capital goods, meaning current treatment facilities should be used for their full lifespan. Hybrid IO LCA’s included additional processes and reduced truncation error increasing overall captured environmental impacts of composting, AD, and incineration by 26, 10 and 26%, respectively. Sensitivity and Monte Carlo analysis evaluate the methods robustness and illustrate the uncertainty of current LCA methods. Major implication: hybrid IO-LCA approaches must become the new norm for LCA. Conclusion This study provided a deeper insight of the overall environmental performance of downstream food waste treatment options including ecological burdens associated with capital goods. Keywords Anaerobic digestion Incineration Composting Food waste Hybrid life cycle assessment Capital good

Shedding Light on the Chemical Diversity of Ectopic Calcifications in Kidney Tissues: Diagnostic and Research Aspects

In most industrialized countries, different epidemiologic studies show that chronic renal failure is dramatically increasing. Such major public health problem is a consequence of acquired systemic diseases such as type II diabetes, which is now the first cause for end stage renal failure. Furthermore, lithogenic diseases may also induce intratubular crystallization, which may finally result in end-stage renal failure (ESRF). Up to now, such rare diseases are often misdiagnosed. In this study, based on twenty four biopsies, we show that SR µFTIR (Synchrotron Radiation-µFourier transform infrared) spectroscopy constitutes a significant opportunity to characterize such pathological µcalcifications giving not only their chemical composition but also their spatial distribution in the tissues. This experimental approach offers new opportunities to the clinicians to describe at the cell level the physico-chemical processes leading to the formation of the pathological calcifications which lead to ESRF

Documento de consenso sobre codificação de exames de ressonância magnética cardíaca em Portugal

One of the obstacles to more frequent and appropriate use of cardiac magnetic resonance (CMR) in Portugal has been the lack of specific codes that accurately describe these examinations as they are currently performed. In this consensus document, recommendations are made for updating and standardizing CMR codes in Portugal. Guidance on which techniques and codes should be used in the most common clinical scenarios is also provided

Exposure of Phosphatidylserine on Leishmania amazonensis Isolates Is Associated with Diffuse Cutaneous Leishmaniasis and Parasite Infectivity

Diffuse cutaneous leishmaniasis (DCL) is a rare clinical manifestation of leishmaniasis, characterized by an inefficient parasite-specific cellular response and heavily parasitized macrophages. In Brazil, Leishmania (Leishmania) amazonensis is the main species involved in DCL cases. In the experimental model, recognition of phosphatidylserine (PS) molecules exposed on the surface of amastigotes forms of L. amazonensis inhibits the inflammatory response of infected macrophages as a strategy to evade the host immune surveillance. In this study, we examined whether PS exposure on L. amazonensis isolates from DCL patients operated as a parasite pathogenic factor and as a putative suppression mechanism of immune response during the infection. Peritoneal macrophages from F1 mice (BALB/c×C57BL/6) were infected with different L. amazonensis isolates from patients with localized cutaneous leishmaniasis (LCL) or DCL. DCL isolates showed higher PS exposure than their counterparts from LCL patients. In addition, PS exposure was positively correlated with clinical parameters of the human infection (number of lesions and time of disease) and with characteristics of the experimental infection (macrophage infection and anti-inflammatory cytokine induction). Furthermore, parasites isolated from DCL patients displayed an increased area in parasitophorous vacuoles (PV) when compared to those isolated from LCL patients. Thus, this study shows for the first time that a parasite factor (exposed PS) might be associated with parasite survival/persistence in macrophages and lesion exacerbation during the course of DCL, providing new insights regarding pathogenic mechanism in this rare chronic disease

Two-electron spin correlations in precision placed donors in silicon

Substitutional donor atoms in silicon are promising qubits for quantum computation with extremely long relaxation and dephasing times demonstrated. One of the critical challenges of scaling these systems is determining inter-donor distances to achieve controllable wavefunction overlap while at the same time performing high fidelity spin readout on each qubit. Here we achieve such a device by means of scanning tunnelling microscopy lithography. We measure anti-correlated spin states between two donor-based spin qubits in silicon separated by 16 ± 1 nm. By utilising an asymmetric system with two phosphorus donors at one qubit site and one on the other (2P−1P), we demonstrate that the exchange interaction can be turned on and off via electrical control of two in-plane phosphorus doped detuning gates. We determine the tunnel coupling between the 2P−1P system to be 200 MHz and provide a roadmap for the observation of two-electron coherent exchange oscillations