Insights on the (Auto)Photocatalysis of Ferritin

Traditionally, ferritin has been considered a photocatalyst capable of photo-oxidizing organic molecules and transferring electrons to external electron acceptors when irradiated by UV–visible light. We have designed new approaches to resolve the uncertainties regarding its photocatalytical mechanism. Experiments with an Fe(II) chelator, an electrochromic indicator, and recombinant ferritin proteins indicate that the excited electrons at the conduction band of the ferritin core do not cross the protein shell. Instead, irradiation causes the electrons to reduce the ferrihydrite core to produce Fe(II) ions. These Fe(II) ions exit the protein shell to reduce electron acceptors. In the absence of electron acceptors or chelators, Fe(II) re-enters ferritin.This work was funded by MINECO and FEDER (CTQ2015-64538). N.S. would like to acknowledge funding from the U.S. Student Fulbright Scholarship

Precursor reaction kinetics control compositional grading and size of CdSe1-xSx nanocrystal heterostructures

We report a method to control the composition and microstructure of CdSe1-xSx nanocrystals by the simultaneous injection of sulfide and selenide precursors into a solution of cadmium oleate and oleic acid at 240 degrees C. Pairs of substituted thio- and selenoureas were selected from a library of compounds with conversion reaction reactivity exponents (k(E)) spanning 1.3 x 10(-5) s(-1) to 2.0 x 10(-1) s(-1). Depending on the relative reactivity (k(Se)/k(S)), core/shell and alloyed architectures were obtained. Growth of a thick outer CdS shell using a syringe pump method provides gram quantities of brightly photoluminescent quantum dots (PLQY = 67 to 90%) in a single reaction vessel. Kinetics simulations predict that relative precursor reactivity ratios of less than 10 result in alloyed compositions, while larger reactivity differences lead to abrupt interfaces. CdSe1-xSx alloys (k(Se)/k(S) = 2.4) display two longitudinal optical phonon modes with composition dependent frequencies characteristic of the alloy microstructure. When one precursor is more reactive than the other, its conversion reactivity and mole fraction control the number of nuclei, the final nanocrystal size at full conversion, and the elemental composition. The utility of controlled reactivity for adjusting alloy microstructure is discussed

Epidermal growth factor receptor expression licenses type-2 helper T cells to function in a T cell receptor-independent fashion

Gastro-intestinal helminth infections trigger the release of interleukin-33 (IL-33), which induces type-2 helper T cells (Th2 cells) at the site of infection to produce IL-13, thereby contributing to host resistance in a T cell receptor (TCR)-independent manner. Here, we show that, as a prerequisite for IL-33-induced IL-13 secretion, Th2 cells required the expression of the epidermal growth factor receptor (EGFR) and of its ligand, amphiregulin, for the formation of a signaling complex between T1/ST2 (the IL-33R) and EGFR. This shared signaling complex allowed IL-33 to induce the EGFR-mediated activation of the MAP-kinase signaling pathway and consequently the expression of IL-13. Lack of EGFR expression on T cells abrogated IL-13 expression in infected tissues and impaired host resistance. EGFR expression on Th2 cells was TCR-signaling dependent, and therefore, our data reveal a mechanism by which antigen presentation controls the innate effector function of Th2 cells at the site of inflammation

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Synthesis and Characterization of Nanoplatelets and Nanoplatelet Heterostructures made with Thiourea and Selone Precursors

In Chapter 1, I give a basic introduction to the scientific background necessary for understanding the rest of the dissertation. I describe semiconductor nanocrystals and quantum confinement, how nanocrystals grow and a brief description of the various characterization methods. Finally, I provide some of the general considerations and chemical sources for the experiments performed in the thesis as a whole. In Chapter 2, I summarize the journey towards working with molecular precursors and show the advances and challenges in modeling and understanding conversion made a step into nanoplatelets more feasible. The chalcogenourea syntheses are not included and the modeling of the spherical nanocrystals is in a fairly summarized form here. This chapter is intended to give a brief overview of the highlights, key conclusions, and resulting questions upon which I designed my own experiments. In Chapter 3, I discuss applying precursor conversion method to nanoplatelets and focus on 3ML CdE growth. I briefly introduce nanoplatelets, explain the new conditions necessary to adapt the chalcogenourea library, demonstrate my efforts in characterizing the kinetics and growth mechanisms, and finally show the relationship of precursor reactivity and final nanoplatelet size. The “kobs catalogue” which summarizes the kinetics and sizing from STEM is an appendix at the end of the chapter. In this chapter, we put to the test the idea that we can control nanocrystal synthesis through precursor reactivity. The synthesis of nanocrystal heterostructures controlled by precursor conversion was discussed in Chapter 2. In Chapter 4, the same theory is applied to nanoplatelet synthetic conditions, but because nanoplatelet nucleation is fast compared to the total reaction time, the precursors should result in something closer to what is modeled without extraneous products. At the end of the chapter, a nanoplatelet alloy catalogue records many of the modeling and alloy experiments. Chapter 5 attempts to gather the various side projects that working with nanoplatelets has brought about. All these projects come together when thinking about how the solute supply and surface ligands might determine nanoplatelet formation, which I hope to shed some insight on. In the end, I hope to have gathered enough information to provide thoughtful answers for why nanoplatelets form, how they are ideal for studying compositional growth, and how nanocrystal alloying changes the structural and optical properties of these materials