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Article ; Online: Aerosolized delivery of ESKAPE pathogens for murine pneumonia models.

Rox, Katharina / Medina, Eva

2024 Volume 14, Issue 1, Page(s) 2558

Abstract: Murine pneumonia models for ESKAPE pathogens serve to evaluate novel antibacterials or to investigate immunological responses. The majority of published models uses intranasal or to a limited extent the intratracheal instillation to challenge animals. In ...

Abstract	Murine pneumonia models for ESKAPE pathogens serve to evaluate novel antibacterials or to investigate immunological responses. The majority of published models uses intranasal or to a limited extent the intratracheal instillation to challenge animals. In this study, we propose the aerosol delivery of pathogens using a nebulizer. Aerosol delivery typically results in homogeneous distribution of the inoculum in the lungs because of lower particle size. This is of particular importance when compounds are assessed for their pharmacokinetic and pharmacodynamic (PK/PD) relationships as it allows to conduct several analysis with the same sample material. Moreover, aerosol delivery has the advantage that it mimics the 'natural route' of respiratory infection. In this short and concise study, we show that aerosol delivery of pathogens resulted in a sustained bacterial burden in the neutropenic lung infection model for five pathogens tested, whereas it gave a similar result in immunocompetent mice for three out of five pathogens. Moreover, a substantial bacterial burden in the lungs was already achieved 2 h post inhalation. Hence, this study constitutes a viable alternative for intranasal administration and a refinement of murine pneumonia models for PK/PD assessments of novel antibacterial compounds allowing to study multiple readouts with the same sample material.
MeSH term(s)	Animals ; Mice ; Respiratory Aerosols and Droplets ; Administration, Inhalation ; Lung ; Pneumonia/drug therapy ; Anti-Bacterial Agents/therapeutic use ; Anti-Bacterial Agents/pharmacokinetics
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2024-01-31
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-52958-9
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Article ; Online: Joint Probabilities Approach to Quantum Games with Noise.

Legón, Alexis R / Medina, Ernesto

Entropy (Basel, Switzerland)

2023 Volume 25, Issue 8

Abstract: A joint probability formalism for quantum games with noise is proposed, inspired by the formalism of non-factorizable probabilities that connects the joint probabilities to quantum games with noise. Using this connection, we show that the joint ... ...

Abstract	A joint probability formalism for quantum games with noise is proposed, inspired by the formalism of non-factorizable probabilities that connects the joint probabilities to quantum games with noise. Using this connection, we show that the joint probabilities are non-factorizable; thus, noise does not generically destroy entanglement. This formalism was applied to the Prisoner's Dilemma, the Chicken Game, and the Battle of the Sexes, where noise is coupled through a single parameter μ. We find that for all the games except for the Battle of the Sexes, the Nash inequalities are maintained up to a threshold value of the noise. Beyond the threshold value, the inequalities no longer hold for quantum and classical strategies. For the Battle of the sexes, the Nash inequalities always hold, no matter the noise strength. This is due to the symmetry and anti-symmetry of the parameters that determine the joint probabilities for that game. Finally, we propose a new correlation measure for the games with classical and quantum strategies, where we obtain that the incorporation of noise, when we have quantum strategies, does not affect entanglement, but classical strategies result in behavior that approximates quantum games with quantum strategies without the need to saturate the system with the maximum value of noise. In this manner, these correlations can be understood as entanglement for our game approach.
Language	English
Publishing date	2023-08-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2014734-X
ISSN	1099-4300 ; 1099-4300
ISSN (online)	1099-4300
ISSN	1099-4300
DOI	10.3390/e25081222
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Article ; Online: Myeloid-derived suppressor cells impair CD4+ T cell responses during chronic Staphylococcus aureus infection via lactate metabolism.

Goldmann, Oliver / Medina, Eva

Cellular and molecular life sciences : CMLS

2023 Volume 80, Issue 8, Page(s) 221

Abstract: Staphylococcus aureus is an important cause of chronic infections resulting from the failure of the host to eliminate the pathogen. Effective S. aureus clearance requires CD4+ T cell-mediated immunity. We previously showed that myeloid-derived suppressor ...

Abstract	Staphylococcus aureus is an important cause of chronic infections resulting from the failure of the host to eliminate the pathogen. Effective S. aureus clearance requires CD4+ T cell-mediated immunity. We previously showed that myeloid-derived suppressor cells (MDSC) expand during staphylococcal infections and support infection chronicity by inhibiting CD4+ T cell responses. The aim of this study was to elucidate the mechanisms underlying the suppressive effect exerted by MDSC on CD4+ T cells during chronic S. aureus infection. It is well known that activated CD4+ T cells undergo metabolic reprogramming from oxidative metabolism to aerobic glycolysis to meet their increased bioenergetic requirements. In this process, pyruvate is largely transformed into lactate by lactate dehydrogenase with the concomitant regeneration of NAD+, which is necessary for continued glycolysis. The by-product lactate needs to be excreted to maintain the glycolytic flux. Using SCENITH (single-cell energetic metabolism by profiling translation inhibition), we demonstrated here that MDSC inhibit CD4+ T cell responses by interfering with their metabolic activity. MDSC are highly glycolytic and excrete large amount of lactate in the local environment that alters the transmembrane concentration gradient and prevent removal of lactate by activated CD4+ T. Accumulation of endogenous lactate impedes the regeneration of NAD+, inhibit NAD-dependent glycolytic enzymes and stop glycolysis. Together, the results of this study have uncovered a role for metabolism on MDSC suppression of CD4+ T cell responses. Thus, reestablishment of their metabolic activity may represent a mean to improve the functionality of CD4+ T cells during chronic S. aureus infection.
MeSH term(s)	Humans ; CD4-Positive T-Lymphocytes/metabolism ; Myeloid-Derived Suppressor Cells ; Staphylococcus aureus/metabolism ; NAD/metabolism ; Staphylococcal Infections/metabolism ; Lactates/metabolism
Chemical Substances	NAD (0U46U6E8UK) ; Lactates
Language	English
Publishing date	2023-07-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-023-04875-9
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Article ; Online: Highly Parallelized Screening of Functionally Enhanced XNA Aptamers in Uniform Hydrogel Particles.

Yik, E J / Medina, E / Paegel, B M / Chaput, John C

ACS synthetic biology

2023 Volume 12, Issue 7, Page(s) 2127–2134

Abstract: Xeno-nucleic acid (XNA) aptamers based on evolvable non-natural genetic polymers hold enormous potential as future diagnostic and therapeutic agents. However, time-consuming and costly procedures requiring the purification of individual XNA sequences ... ...

Abstract	Xeno-nucleic acid (XNA) aptamers based on evolvable non-natural genetic polymers hold enormous potential as future diagnostic and therapeutic agents. However, time-consuming and costly procedures requiring the purification of individual XNA sequences produced by large-scale polymerase-mediated primer extension reactions pose a major bottleneck to the discovery of highly active XNA motifs for biomedical applications. Here, we describe a straightforward approach for rapidly surveying the binding properties of XNA aptamers identified by in vitro selection. Our strategy involves preparing XNA aptamer particles in which many copies of the same aptamer sequence are distributed throughout the gel matrix of a polyacrylamide-encapsulated magnetic particle. Aptamer particles are then screened by flow cytometry to assess target binding affinity and deduce structure-activity relationships. This generalizable and highly parallel assay dramatically accelerates the pace of secondary screening by allowing a single researcher to evaluate 48-96 sequences per day.
MeSH term(s)	Nucleic Acids/chemistry ; Aptamers, Nucleotide/genetics ; Hydrogels ; SELEX Aptamer Technique/methods ; Structure-Activity Relationship
Chemical Substances	Nucleic Acids ; Aptamers, Nucleotide ; Hydrogels
Language	English
Publishing date	2023-07-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2161-5063
ISSN (online)	2161-5063
DOI	10.1021/acssynbio.3c00189
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Book ; Online: Merging of Dirac points through uniaxial modulation on an optical lattice

López, A. / Montañes, B. / Medina, E.

2023

Abstract: We analyze the scenario of modulating the potential strength of bound atoms in an optical honeycomb lattice patterned by an electric field to emulate uniaxial strain. This modulation can be achieved by a combination of the strength of the patterned ... ...

Abstract	We analyze the scenario of modulating the potential strength of bound atoms in an optical honeycomb lattice patterned by an electric field to emulate uniaxial strain. This modulation can be achieved by a combination of the strength of the patterned electric field and gauge vector effects using the Floquet approach. We show that such a modulation allows one to follow through a topological transition between a semi-metal and a band insulator, when two non-equivalent $K$ points merge as a function of the electric field strength. We explicitly compute the wavefunctions for the moving $K$ points and the Chern numbers up to the transition. Anisotropic effective masses and the insulating gap are described close to the semimetal-insulator transition. Comment: 12 pages, 5 figures
Keywords	Condensed Matter - Materials Science
Publishing date	2023-03-03
Publishing country	us
Document type	Book ; Online
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Article: Forensic Identification in the Aftermath of Human Rights Crimes in Chile: A Decentered Computer History.

Medina, Eden

Technology and culture

2018 Volume 59, Issue 4S, Page(s) S100–S133

Abstract: As computer historians extend the bounds of what constitutes computer history, they must also take care not to write histories that overstate the importance of these technologies. "Decentering" the computer in computer history provides a way for ... ...

Abstract	As computer historians extend the bounds of what constitutes computer history, they must also take care not to write histories that overstate the importance of these technologies. "Decentering" the computer in computer history provides a way for historians to study the role of computers in more domains without exaggerating their importance. Here I illustrate how the use of a computer system for forensic identification formed part of Chile's complicated history of truth, justice, and reconciliation in the aftermath of the Pinochet dictatorship. While computers are not, and should not be, the central focus of how we understand processes of truth and reconciliation in history, in this case they illuminate the dynamics of how those working within the Chilean government, including its justice system, have approached Chile's history of human rights abuses.
MeSH term(s)	Chile ; Computers/history ; Crime/history ; Crime/statistics & numerical data ; Forensic Sciences/history ; Forensic Sciences/statistics & numerical data ; History, 20th Century ; History, 21st Century ; Human Rights/history ; Humans ; Social Justice/history
Language	English
Publishing date	2018-12-27
Publishing country	United States
Document type	Historical Article ; Journal Article
ZDB-ID	2021131-4
ISSN	1097-3729 ; 0040-165X
ISSN (online)	1097-3729
ISSN	0040-165X
DOI	10.1353/tech.2018.0151
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Article ; Online: Dilemma breaking in quantum games by joint probabilities approach.

Legón, Alexis R / Medina, Ernesto

Scientific reports

2022 Volume 12, Issue 1, Page(s) 13470

Abstract: Classical games get fundamentally modified in the quantum realm because of non-locality and entanglement, that bypass some of the crucial features of the classical problem that define a dilemma. We will analyze how the dilemma can be shunted and even ... ...

Abstract	Classical games get fundamentally modified in the quantum realm because of non-locality and entanglement, that bypass some of the crucial features of the classical problem that define a dilemma. We will analyze how the dilemma can be shunted and even completely eliminated by the players using quantum strategies from the viewpoint of joint probabilities. In this approach, the game information (entropy) needs to be incorporated into the game strategies. We also connect the potential of the formalism of quantum games with the transmission of quantum information in quantum noisy channels and recent considerations of the connection between thermalization mechanisms in statistical mechanics, the many body problem and cooperative games considered here in the quantum regime.
Language	English
Publishing date	2022-08-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-17072-8
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Article ; Online: Mechanisms underlying immunosuppression by regulatory cells.

Goldmann, Oliver / Nwofor, Obiageli Vivian / Chen, Qian / Medina, Eva

Frontiers in immunology

2024 Volume 15, Page(s) 1328193

Abstract: Regulatory cells, such as regulatory T cells (Tregs), regulatory B cells (Bregs), and myeloid-derived suppressor cells (MDSCs), play a crucial role in preserving immune tolerance and controlling immune responses during infections to prevent excessive ... ...

Abstract	Regulatory cells, such as regulatory T cells (Tregs), regulatory B cells (Bregs), and myeloid-derived suppressor cells (MDSCs), play a crucial role in preserving immune tolerance and controlling immune responses during infections to prevent excessive immune activation. However, pathogens have developed strategies to hijack these regulatory cells to decrease the overall effectiveness of the immune response and persist within the host. Consequently, therapeutic targeting of these immunosuppressive mechanisms during infection can reinvigorate the immune response and improve the infection outcome. The suppressive mechanisms of regulatory cells are not only numerous but also redundant, reflecting the complexity of the regulatory network in modulating the immune responses. The context of the immune response, such as the type of pathogen or tissue involved, further influences the regulatory mechanisms involved. Examples of these immunosuppressive mechanisms include the production of inhibitory cytokines such as interleukin 10 (IL-10) and transforming growth factor beta (TGF-β) that inhibit the production of pro-inflammatory cytokines and dampen the activation and proliferation of effector T cells. In addition, regulatory cells utilize inhibitory receptors like cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) to engage with their respective effector cells, thereby suppressing their function. An alternative approach involves the modulation of metabolic reprogramming in effector immune cells to limit their activation and proliferation. In this review, we provide an overview of the major mechanisms mediating the immunosuppressive effect of the different regulatory cell subsets in the context of infection.
MeSH term(s)	T-Lymphocytes, Regulatory ; Immune Tolerance ; Cytokines ; Transforming Growth Factor beta ; Immunosuppression Therapy
Chemical Substances	Cytokines ; Transforming Growth Factor beta
Language	English
Publishing date	2024-02-06
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1328193
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Article ; Online: Health impacts in pathology workforce during mergers and acquisitions (M&A).

Chiou, Paul Zone / Herring, R Patti / Oh, Jisoo / Medina, Ernest

Journal of clinical pathology

2024 Volume 77, Issue 2, Page(s) 98–104

Abstract: Aims: To compare burn-out in laboratory professionals (LPs) with exposure to consolidation to those without, and to investigate the role of social support as a moderator in the exposure to mergers and acquisitions (M&A).: Methods: Surveys were sent ... ...

Abstract	Aims: To compare burn-out in laboratory professionals (LPs) with exposure to consolidation to those without, and to investigate the role of social support as a moderator in the exposure to mergers and acquisitions (M&A). Methods: Surveys were sent to the clinical LPs, including 732 with exposure to M&A and 819 without. The dependent variable was burn-out, and the independent variable was exposure to M&A. In investigating the role of social support in exposure group, a logistic regression was used with education, time since M&A, gender, merger types, practice setting, lab hierarchy and race as covariates. Results: Exposure to M&A was associated with higher levels of burn-out (p<0.05). In logistic regression of the workforce exposed to M&A, the odds for LP developing a high level of burn-out are lowered by 7.1% for every unit of increase in social support (OR 0.93; 95% CI 0.88 to 0.98; p=0.004). Conclusion: LPs exposed to M&A are more likely to experience higher levels of burn-out but having social support can protect against burn-out, which has policy implications for leadership managing laboratories in times of M&A.
MeSH term(s)	Humans ; Lipopolysaccharides ; Health Facility Merger ; Workforce ; Surveys and Questionnaires
Chemical Substances	Lipopolysaccharides
Language	English
Publishing date	2024-01-18
Publishing country	England
Document type	Journal Article
ZDB-ID	80261-x
ISSN	1472-4146 ; 0021-9746
ISSN (online)	1472-4146
ISSN	0021-9746
DOI	10.1136/jcp-2023-209124
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Article ; Online: FSGS and COVID-19 in Non-African American Patients.

Medina, Elba / Rueda, Carlos / Batlle, Daniel

Kidney360

2023 Volume 4, Issue 5, Page(s) 687–699

Abstract: Collapsing Focal Segmental Glomerulosclerosis (FSGS) has been reported relatively frequently in African American (AA) patients with coronavirus disease 2019 (COVID-19), and it is associated almost always with Apolipoprotein L gen 1 (APOL1) high-risk ... ...

Abstract	Collapsing Focal Segmental Glomerulosclerosis (FSGS) has been reported relatively frequently in African American (AA) patients with coronavirus disease 2019 (COVID-19), and it is associated almost always with Apolipoprotein L gen 1 (APOL1) high-risk variants. We reviewed the published literature from April 2020 to November 2022 searching for non-African American (non-AA) patients with FSGS associated with COVID-19 (eight White patients, six Hispanic patients, three Asian patients, one Indian patient, and one Asian Indian patient). The following histologic patterns were found: collapsing (n=11), not otherwise specified (n=5), tip (n=2), and perihilar (n=1). Fifteen of the 19 patients had AKI. The APOL1 genotype was reported in only six of the 19 non-AA patients. Three of them (two Hispanic patients and one White patient) with collapsing FSGS had high-risk APOL1 variants. The other three patients (two White patients and one Hispanic patient with the collapsing variant, tip variant, and not otherwise specified) had low-risk APOL1 variants. Among 53 African American patients with collapsing FSGS associated with COVID-19, 48 had high-risk APOL1 variants and five had low-risk APOL1 variants. We conclude that in non-AA patients, FSGS is a rare complication of COVID-19. FSGS associated with COVID-19 can occur rarely with low-risk APOL1 variants in non-AA and AA patients. Non-AA patients reported to be associated with high-risk APOL1 variants possibly reflect inaccuracy of self-reported race with AA admixture because of unknown ancestry. Given the importance of APOL1 in the pathogenesis of FSGS associated with viral infection and to avoid racial bias, it seems appropriate that APOL1 testing be considered in patients with FSGS associated with COVID-19, regardless of self-reported race.
MeSH term(s)	Humans ; United States/epidemiology ; Glomerulosclerosis, Focal Segmental/genetics ; Glomerulosclerosis, Focal Segmental/pathology ; Apolipoprotein L1/genetics ; COVID-19/genetics ; Genotype
Chemical Substances	Apolipoprotein L1 ; APOL1 protein, human
Language	English
Publishing date	2023-05-25
Publishing country	United States
Document type	Review ; Journal Article
ISSN	2641-7650
ISSN (online)	2641-7650
DOI	10.34067/KID.0000000000000104
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