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were identified in 41% and 69% of the samples, respectively. The prevalence of the identified parasites increased in permanent aviaries on the second sampling date. In contrast, birds kept in seminatural free-flight aviaries in line with the "born to be free" rearing method had a lower prevalence of these parasites. Galliformes housed in seminatural aviaries may be better prepared for reintroduction to their natural habitats.Bone-marrow mesenchymal stromal cells (MSCs) are abnormal in multiple myeloma (MM) and play a critical role by promoting growth, survival and drug resistance of MM cells. We observed higher Toll-like receptor 4 (TLR4) gene expression in MM MSCs than in MSCs from healthy donors. At the clinical level, we highlighted that TLR4 expression in MM MSCs evolves in parallel with the disease stage. Thus, we reasoned that the TLR4 axis is pivotal in MM by increasing the pro-tumor activity of MSCs. Challenging primary MSCs with TLR4 agonists increased the expression of CD54 and interleukin 6, two factors directly implicated in MM MSC-MM cell crosstalk. Then, we evaluated the therapeutic efficacy of a TLR4 antagonist combined or not with conventional treatment in vitro with MSC-MM cell co-culture and in vivo with the Vk*MYC mouse model. Selective inhibition of TLR4 specifically reduced the MM MSC ability to support growth of MM cells in an IL-6-dependent manner and delayed the development of MM in the Vk*MYC mouse model by altering the early disease phase in vivo. For the first time, we demonstrate that specific targeting of the pathological bone-marrow microenvironment via TLR4 signaling could be an innovative approach to alter MM pathology development.The Darwin's fox (Lycalopex fulvipes) is one of the most endangered carnivores worldwide, with the risk of disease spillover from domestic dogs being a major conservation threat. However, lack of epidemiologic information about generalist, non-dog-transmission-dependent protozoal and bacterial pathogens may be a barrier for disease prevention and management. To determine the exposure of some of these agents in Darwin's fox populations, 54 serum samples were collected from 47 Darwin's foxes in Southern Chile during 2013-18 and assessed for the presence of antibodies against Brucella abortus, Brucella canis, Coxiella burnetii, pathogenic Leptospira (serovars Grippotyphosa, Pomona, Canicola, Hardjo, and Copehageni), Toxoplasma gondii, and Neospora caninum. The highest seroprevalence was detected for T. gondii (78%), followed by pathogenic Leptospira (14%). All the studied Leptospira serovars were confirmed in at least one animal. Two foxes seroconverted to Leptospira and one to T. gondii during the study period. No seroconversions were observed for the other pathogens. No risk factors, either intrinsic (sex, age) or extrinsic (season, year, and degree of landscape anthropization), were associated with the probability of being exposed to T. gondii. Our results indicate that T. gondii exposure is widespread in the Darwin's fox population, including in areas with minimal anthropization, and that T. gondii and pathogenic Leptospira might be neglected threats to the species. Further studies identifying the causes of morbidity and mortality in Darwin's fox are needed to determine if these or other pathogens are having individual or population-wide effects in this species.Plasmablastic-lymphoma (PBL) represents a clinically heterogeneous subtype of aggressive-B-cell-non-Hodgkin-lymphoma. Although targeted-sequencing-studies and a single-center whole-exome-sequencing (WES) study in HIV+ patients recently revealed several genes, associated with PBL-pathogenesis, the global mutational-landscape and transcriptional-profile of PBL remain elusive. To inform on disease-associated mutational-drivers, mutational-patterns and perturbed pathways in HIV+ and HIV-PBL we performed WES and transcriptome sequencing (RNA-seq) of 33 PBL-tumors. Integrative analysis of somatic-mutations and gene-expression-profiles were performed to acquire insights into the divergent genotype-phenotype-correlation in EBV+ and EBV-PBL. We describe a significant accumulation of mutations in the Janus-kinase-signal-transducer and transcription-activator (OSMR, STAT3, PIM1, SOCS1) as well as receptor tyrosine-kinase RAS-pathways (ERBB3, NRAS, PDGFRB, NTRK). We provide further evidence of frequent perturbance of nuclear-factor κB (NFκB) signaling (NFKB2, BTK). Induced pathways, identified by RNA-seq closely resemble the mutational-profile regarding alterations accentuated in IL-6/JAK/STAT-signaling, NFκB-activity and MYC-signaling. Moreover, class I-MHC mediated antigen-processing and cell-cycle-regulation were significantly impacted by the EBV-status. An almost exclusive upregulation of PI3K/AKT/MTOR-signaling in EBV+ PBL and a significantly induced expression of NTRK3 in concert with recurrent oncogenic-mutations in EBV- PBL, hints at specific therapeutically targetable-mechanism in PBL-subgroups. Our characterization of a mutational and transcriptomic-landscape in PBL, distinct from DLBCL and MM substantiates the pathobiological-independence of PBL in the spectrum of B-cell-malignancies and thereby refines the taxonomy for aggressive-lymphomas.As of January 2021, the U.S. Food and Drug Administration has approved four radiation exposure medical countermeasures (MCMs) to treat hematological acute effects, but no MCM is yet approved for radiation-induced lung injury (RILI). MCM approval for RILI and other subsyndromes utilizes the FDA Animal Efficacy Rule (Animal Rule), that requires demonstration of MCM efficacy in animal models with well-characterized pathophysiology, therefore, allowing translation to human use. A good animal model replicates the clinical condition and natural history of the disease, while allowing for studying the mechanism of action of the applied MCM and exhibiting clear benefits in terms of primary and secondary endpoints. However, there is much conversation regarding the advantages and limitations of individual models, and how to properly apply these models to demonstrate MCM efficacy. On March 20, 2019, the Radiation and Nuclear Countermeasures Program (RNCP) within the National Institute of Allergy and Infectious Diseases (NIAID), Food and Drug Administration (FDA), and the Biomedical Advanced Research and Development Authority (BARDA) sponsored a workshop to identify critical research gaps, discuss current clinical practices for different types of pulmonary diseases, and consider available animal models for RILI.Triple-negative breast cancer (TNBC) is associated with a worse prognosis and higher mortality than other breast cancers, and intensive effort has been made to develop therapies targeting TNBC. TNBC shows higher expression levels of programmed cell death ligand 1 (PD-L1) than other breast cancer types, which leads to a decrease in the killing effects of CD8+ T cells in the tumor microenvironment. Inhibitors of apoptosis proteins (IAPs) could prevent cell death through suppressing caspase activity. Here, Birinapant, an antagonist of IAPs, was found to promote the tumor infiltration of CD8+ T cells via increasing the secretion of the chemokine CXCL9. In addition, Birinapant could inhibit tumor growth via increasing the secretion of and the sensitivity to TNF-α in a TNBC xenotransplantation mouse model. Consequently, liposomes encapsulating Birinapant and siPD-L1 mediated a form of combination therapy based on two drugs to significantly increase the therapeutic effects toward TNBC.Doped silicon nanocrystals (SiNCs) are promising materials that could find use in a wide variety of applications. Realizing methods to tailor the surface chemistry of these particles offers greater tunability of the material properties as well as broader solvent compatibility. Herein, we report organic-soluble B-doped SiNCs prepared via a thermal processing method followed by phosphorus pentachloride etching induced functionalization with alkoxy ligands of varied chain lengths. This approach provides a scalable route to solution processable B-doped SiNCs and establishes a potential avenue for the functionalization of other doped SiNCs.The hydration of amino acids closely correlates the hydration of peptides and proteins and is critical to their biological functions. However, complete and quantitative understanding about the hydration of amino acids is lacking. Here, tightly and loosely bound water of 20 zwitterionic amino acids are quantitatively distinguished and determined by Raman spectroscopy with multivariate curve resolution (Raman-MCR) and differential scanning calorimetry (DSC). The total hydration water obtained from Raman-MCR and the tightly bound water determined by DSC have certain relevance, but they do not exactly correspond. In particular, Pro, Arg and Lys exhibit larger number of tightly bound water molecules (4.02-6.59), showing a significant influence on the onset transition temperature and the melting enthalpy values of water molecules, which provides direct evidence for their unique functions associated with biological water. Asn, Ser, Thr, Met, His and Glu have a smaller number of tightly bound water molecules (0.30-1.31), whilst the other remaining 11 amino acids only contain loosely bound water molecules. Four exceptional amino acids Ile, Leu, Phe and Val show fewer tightly bound water molecules but a higher number of loosely bound water molecules. As for the hydration shell structure, most amino acids except Pro and Trp enhance tetrahedral water structure and H-bonds relative to pure water and at least 1.9% of the hydration water molecules associated with the amino acids show non-hydrogen-bonded OH defects. This work combines two effective experimental techniques to reveal the hydration water structure and quantitatively analyze two kinds of bound water molecules of 20 amino acids.Thermoresponsive microgels are a popular model system to study phase transitions in soft matter, because temperature directly controls their volume fraction. Ionic microgels are additionally pH-responsive and possess a rich phase diagram. Although effective interaction potentials between microgel particles have been proposed, these have never been fully tested, leading to a gap in our understanding of the link between single-particle and collective properties. To help resolve this gap, four sets of ionic microgels with varying crosslinker density were synthesised and characterised using light scattering techniques and confocal microscopy. The resultant structural and dynamical information was used to investigate how particle softness affects the phase behaviour of ionic microgels and to validate the proposed interaction potential. We find that the architecture of the microgel plays a marked role in its phase behaviour. Rather than the ionic charges, it is the dangling ends which drive phase transitions and interactions at low concentration. Comparison to theory underlines the need for a refined theoretical model which takes into consideration these close-contact interactions.It is difficult for the same molecule to self-assemble into stable vesicular particles in water and aliphatic hydrocarbon (oil), respectively. Everolimus in vivo Here we demonstrated that chiral oligo(methylene-p-phenyleneethynylene)s with alternating hydrophilic and hydrophobic side chains were able to self-assemble into vesicular particles independent of solvent polarity. These particles were well dispersed in aliphatic hydrocarbon, alcohol or water for at least one month at room temperature, and readily transferred from organic to aqueous phases via dialysis. They displayed a noticeable response to the acidity of the aqueous phase, and could be used as simple cargos for loading hydrophilic or hydrophobic molecules in aqueous cores, which were different from loading in polymersomes. The vesicular particles loaded with hydrophobic paclitaxel exhibited comparable anti-HeLa cell activity to free paclitaxel in vitro.