To date the concept of the bioeconomy - an economy based primarily on biogenic instead
of fossil resources - has largely been associated with visions of "green growth" and the advancement
of ...biotechnology and has been framed from within an industrial perspective. However, there is
no consensus as to what a bioeconomy should effectively look like, and what type of society it
would sustain. In this paper, we identify different types of narratives constructed around this
concept and carve out the techno-political implications they convey. We map these narratives
on a two-dimensional option space, which allows for a rough classification of narratives and
their related imaginaries into four paradigmatic quadrants. We draw the narratives from three
different sources: (i) policy documents of national and supra-national authorities; (ii) stakeholder
interviews; and (iii) scenarios built in a biophysical modelling exercise. Our analysis shows that there
is a considerable gap between official policy papers and visions supported by stakeholders. At least
in the case of Austria there is also a gap between the official strategies and the option space identified
through biophysical modelling. These gaps testify to the highly political nature of the concept of the
bioeconomy and the diverging visions of society arising from it.
We evaluated the prognostic value of Sarcopenia, low precardial adipose-tissue (PAT), and high tumor-volume in the outcome of surgically-treated pleural mesothelioma (PM).
From 2005 to 2020, ...consecutive surgically-treated PM-patients having a pre-operative computed tomography (CT) scan were retrospectively included. Sarcopenia was assessed by CT-based parameters measured at the level of the fifth thoracic vertebra (TH5) by excluding fatty-infiltration based on CT-attenuation. The findings were stratified for gender, and a threshold of the 33rd percentile was set to define sarcopenia. Additionally, tumor volume as well as PAT were measured. The findings were correlated with progression-free survival and long-term mortality.
Two-hundred-seventy-eight PM-patients (252 male; 70.2 ± 9 years) were included. The mean progression-free survival was 18.6 ± 12.2 months, and the mean survival time was 23.3 ± 24 months. Progression was associated with chronic obstructive pulmonary disease (COPD) (
= <0.001), tumor-stage (
= 0.001), and type of surgery (
= 0.026). Three-year mortality was associated with higher patient age (
= 0.005), presence of COPD (
< 0.001), higher tumor-stage (
= 0.015), and higher tumor-volume (
< 0.001). Kaplan-Meier statistics showed that sarcopenic patients have a higher three-year mortality (
= 0.002). While there was a negative correlation of progression-free survival and mortality with tumor volume (r = 0.281,
= 0.001 and r = -0.240,
< 0.001; respectively), a correlation with PAT could only be shown for epithelioid PM (
= 0.040).
Sarcopenia as well as tumor volume are associated with long-term mortality in surgically treated PM-patients. Further, while there was a negative correlation of progression-free survival and mortality with tumor volume, a correlation with PAT could only be shown for epithelioid PM.
Immunotherapies, such as chimeric antigen receptor (CAR) modified T cells and antibody‐drug conjugates (ADCs), have revolutionized the treatment of cancer, especially of lymphoid malignancies. The ...application of targeted immunotherapy to patients with acute myeloid leukemia (AML) has been limited in particular by the lack of a tumor‐specific target antigen. Gemtuzumab ozogamicin (GO), an ADC targeting CD33, is the only approved immunotherapeutic agent in AML. In our study, we introduce a CD33‐directed third‐generation CAR T‐cell product (3G.CAR33‐T) for the treatment of patients with AML. 3G.CAR33‐T cells could be expanded up to the end‐of‐culture, that is, 17 days after transduction, and displayed significant cytokine secretion and robust cytotoxic activity when incubated with CD33‐positive cells including cell lines, drug‐resistant cells, primary blasts as well as normal hematopoietic stem and progenitor cells (HSPCs). When compared to second‐generation CAR33‐T cells, 3G.CAR33‐T cells exhibited higher viability, increased proliferation and stronger cytotoxicity. Also, GO exerted strong antileukemia activity against CD33‐positive AML cells. Upon genomic deletion of CD33 in HSPCs, 3G.CAR33‐T cells and GO preferentially killed wildtype leukemia cells, while sparing CD33‐deficient HSPCs. Our data provide evidence for the applicability of CD33‐targeted immunotherapies in AML and its potential implementation in CD33 genome‐edited stem cell transplantation approaches.
What's new?
In the development of immunotherapy for acute myeloid leukemia (AML), a target of interest is CD33, which is expressed on blast cells in more than 90 percent of AML patients. CD33 is also expressed on healthy myeloid and progenitor cells, however, raising the risk for off‐target effects with CD33 therapies. Here, the authors introduce a CD33‐directed third‐generation chimeric antigen receptor (CAR) T‐cell product (3G.CAR33‐T). 3G.CAR33‐T cells were effective against CD33‐positive cells, including AML blasts, and successfully overcame AML drug resistance. Genomic deletion of CD33 in hematopoietic stem and progenitor cells resulted in preferential killing of leukemia cells by 3G.CAR33‐T cells.
Proteins of the lipocalin family are known to bind small hydrophobic ligands and are involved in various physiological processes ranging from lipid transport to oxidative stress responses. The genome ...of the malaria parasite Plasmodium falciparum contains a single protein PF3D7_0925900 with a lipocalin signature. Using crystallography and small-angle X-ray scattering, we show that the protein has a tetrameric structure of typical lipocalin monomers; hence we name it P. falciparum lipocalin (PfLCN). We show that PfLCN is expressed in the intraerythrocytic stages of the parasite and localizes to the parasitophorous and food vacuoles. Conditional knockdown of PfLCN impairs parasite development, which can be rescued by treatment with the radical scavenger Trolox or by temporal inhibition of hemoglobin digestion. This suggests a key function of PfLCN in counteracting oxidative stress-induced cell damage during multiplication of parasites within erythrocytes.
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•Crystal structure of the malaria parasite lipocalin•Comparative analysis of lipocalin superfamily members in alveolate genomes•Localization of PfLipocalin to the parasitophorous vacuole and food vacuole•Reverse genetics reveal PfLipocalin function in oxidative damage control
Lipocalins are a structurally conserved family of proteins and are known to bind to small hydrophobic molecules. Burda et al. identify a lipocalin in the malaria parasite using structural analysis and show that it has a function in oxidative damage control that is important for parasite growth.
The vibronic properties of two dimeric iron (II) high-spin complexes
5
CpFeX
2
(
5
Cp = Pentaisopropyl-cyclopentadienyl, X = OH-(
1
), Br-(
2
)) have been studied using nuclear inelastic scattering ...(NIS). In order to assign the experimentally observed bands to the particular modes, theoretical calculations using density functional theory (DFT) have been performed based on the structural data obtained by X-ray crystallography. The calculated partial density of vibrational states (pDOS) reproduces the experimental data. Thus, we were able to assign almost each of the experimentally observed NIS bands to their corresponding molecular vibrational modes.
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