Colloidal motility and pattern formation under rectified diffusiophoresis

In this letter, we characterize experimentally the diffusiophoretic motion of colloids and lambda- DNA toward higher concentration of solutes, using microfluidic technology to build spatially- and temporally-controlled concentration gradients. We then demonstrate that segregation and spatial patterning of the particles can be achieved from temporal variations of the solute concentration profile. This segregation takes the form of a strong trapping potential, stemming from an osmotically induced rectification mechanism of the solute time-dependent variations. Depending on the spatial and temporal symmetry of the solute signal, localization patterns with various shapes can be achieved. These results highlight the role of solute contrasts in out-of-equilibrium processes occuring in soft matter

Managing the necessary cross-disciplinary approach to organic farming research programmes: example of an organic bread programme.

This programme was developed within a cross-disciplinary approach resulting from five project proposals focusing on the organic wheat, flour and bread sector. More than 30 researchers from nine academic research laboratories, five technical centres, three development agencies and four industrial firms were involved in the project, covering a large area of expertise (from genetics to sociology). The programme adopted a reverse engineering approach, starting from consumer expectations and travelling, link-by-link, up the food chain. A qualitative study of consumer perception and expectations showed that organic bread was perceived as a natural, nourishing and healthy product, and that although its organoleptic characteristics (volume, texture, etc.) were a determining factor, they in no way totally accounted for the quality of the product. Nutritional value and safety must also be taken into consideration, especially in the case of occasional consumers. Based on this study, work was undertaken to find processing conditions to turn grain into flour and flour into bread, which would meet those expectations. New roller milling diagrams were developed at the industrial scale in order to produce flour with higher fibre and micronutrient contents. Studies of the bread-making process have shown that higher levels of lactic acid bacterium production in millstone flour are probably linked to its mineral content. A more acidic environment, due to sourdough fermentation, increases phytasic activity (improving digestibility) and increases mineral bioavailability, including magnesium. Based on those findings, prototype breads were developed and assessed by two panels of 60 people in two different regions of France. The results showed that it was possible to produce bread that satisfied consumers’ sensory and nutritional expectations by adapting the fractionation processes during bread-making according to the characteristics of the wheat. Finally, this programme resulted in a large number of publications and created a dynamic process between participants. It served as the backbone for several complementary satellite programmes that enhanced the original research while being integrated and supported by the project management committee

Characterization of surface Ag nanoparticles in nanocomposite a-C:Ag coatings by grazing incidence X-ray diffraction at sub-critical angles of incidence

Silver diffusion within nanocomposite films and/or toward the film surface is often observed during annealing of the silver-based nanocomposite films. In order to control and/or minimize this process, it is crucial to characterize the aggregated silver nanoparticles on the films surface. In this paper grazing incidence X-ray diffraction (GIXRD) with both sub-critical and supra-critical angles of incidence is used to characterize the Ag nanoparticles distribution, shape and structure both inside the matrix and on the nanocomposite film surface. The nanocomposite carbon coating containing Ag nanoparticles (a-C:Ag) was deposited by dc magnetron sputtering. The coatings were analyzed by GIXRD using fixed incident angles both below and above the critical angle for total reflection. By using sub-critical angles it was possible to eliminate diffraction from the bulk material allowing to estimate the size distribution of the nanoparticles sitting on the surface. The results obtained by GIXRD analysis were checked through comparison with the observations made by both TEM and SEM analysis. The proposed methodology can be used to characterized nanoparticles deposition on a surface and/or island formation during film growth as long an adequate substrate with high critical angle for total reflection is used.We gratefully acknowledge the financial support provided by the FCT—Fundação para a Ciência e Tecnologia and FSE for the grant SFRH/BD/82472/2011. This research is sponsored by the FEDER funds through the program COMPETE—Programa Operacional Factores de Competitividade and by the national funds through FCT—Fundação para a Ciência e Tecnologia in the framework of the Strategic Projects PEST C/EME/UIO0285/2011

Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca's large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells

Loss of HOP tumour suppressor expression in head and neck squamous cell carcinoma

We report that homeodomain-only protein (HOP) is expressed in the suprabasal layer of normal upper aerodigestive tract epithelium and expression strongly decreases in hypopharyngeal carcinoma. Interestingly, HOP has very recently been shown to be a tumour suppressor involved in differentiation, suggesting that HOP may have a similar role in head and neck squamous cell carcinoma (HNSSC)

Advanced MR techniques for preoperative glioma characterization: part 1 (vol 57, pg 1655, 2023)

Radiolog

Functional Maturation of Induced Pluripotent Stem Cell Hepatocytes in Extracellular Matrix-A Comparative Analysis of Bioartificial Liver Microenvironments

Induced pluripotent stem cells (iPSCs) are new diagnostic and potentially therapeutic tools to model disease and assess the toxicity of pharmaceutical medications. A common limitation of cell lineages derived from iPSCs is a blunted phenotype compared with fully developed, endogenous cells. We examined the influence of novel three-dimensional bioartificial microenvironments on function and maturation of hepatocyte-like cells differentiated from iPSCs and grown within an acellular, liver-derived extracellular matrix (ECM) scaffold. In parallel, we also compared a bioplotted poly-L -lactic acid (PLLA) scaffold that allows for cell growth in three dimensions and formation of cell-cell contacts but is infused with type I collagen (PLLA-collagen scaffold) alone as a "deconstructed" control scaffold with narrowed biological diversity. iPSC-derived hepatocytes cultured within both scaffolds remained viable, became polarized, and formed bile canaliculi-like structures; however, cells grown within ECM scaffolds had significantly higher P450 (CYP2C9, CYP3A4, CYP1A2) mRNA levels and metabolic enzyme activity compared with iPSC hepatocytes grown in either bioplotted PLLA collagen or Matrigel sandwich control culture. Additionally, the rate of albumin synthesis approached the level of primary cryopreserved hepatocytes with lower transcription of fetal-specific genes, alpha-fetoprotein and CYP3A7, compared with either PLLA-collagen scaffolds or sandwich culture. These studies show that two acellular, three-dimensional culture systems increase the function of iPSC-derived hepatocytes. However, scaffolds derived from ECM alone induced further hepatocyte maturation compared with bioplotted PLLA-collagen scaffolds. This effect is likely mediated by the complex composition of ECM scaffolds in contrast to bioplotted scaffolds, suggesting their utility for in vitro hepatocyte assays or drug discovery. SIGNIFICANCE Through the use of novel technology to develop three-dimensional (3D) scaffolds, the present study demonstrated that hepatocyte-like cells derived via induced pluripotent stem cell (iPSC) technology mature on 3D extracellular matrix scaffolds as a result of 3D matrix structure and scaffold biology. The result is an improved hepatic phenotype with increased synthetic and catalytic potency, an improvement on the blunted phenotype of iPSC-derived hepatocytes, a critical limitation of iPSC technology. These findings provide insight into the influence of 3D microenvironments on the viability, proliferation, and function of iPSC hepatocytes to yield a more mature population of cells for cell toxicity studies and disease modeling

Advanced MR techniques for preoperative glioma characterization: part 2 (vol 57, pg 1676, 2023)

Radiolog

Molecular Pathogenesis of Post-Transplant Acute Kidney Injury: Assessment of Whole-Genome mRNA and MiRNA Profiles.

Acute kidney injury (AKI) affects roughly 25% of all recipients of deceased donor organs. The prevention of post-transplant AKI is still an unmet clinical need. We prospectively collected zero-hour, indication as well as protocol kidney biopsies from 166 allografts between 2011 and 2013. In this cohort eight cases with AKI and ten matched allografts without pathology serving as control group were identified with a follow-up biopsy within the first twelve days after engraftment. For this set the zero-hour and follow-up biopsies were subjected to genome wide microRNA and mRNA profiling and analysis, followed by validation in independent expression profiles of 42 AKI and 21 protocol biopsies for strictly controlling the false discovery rate. Follow-up biopsies of AKI allografts compared to time-matched protocol biopsies, further baseline adjustment for zero-hour biopsy expression level and validation in independent datasets, revealed a molecular AKI signature holding 20 mRNAs and two miRNAs (miR-182-5p and miR-21-3p). Next to several established biomarkers such as lipocalin-2 also novel candidates of interest were identified in the signature. In further experimental evaluation the elevated transcript expression level of the secretory leukocyte peptidase inhibitor (SLPI) in AKI allografts was confirmed in plasma and urine on the protein level (p<0.001 and p = 0.003, respectively). miR-182-5p was identified as a molecular regulator of post-transplant AKI, strongly correlated with global gene expression changes during AKI. In summary, we identified an AKI-specific molecular signature providing the ground for novel biomarkers and target candidates such as SLPI and miR-182-5p in addressing AKI

Elevated Incidence of Fractures in Solid-Organ Transplant Recipients on Glucocorticoid-Sparing Immunosuppressive Regimens

This study was conducted to assess the occurrence of fractures in solid-organ transplant recipients. Methods. Medical record review and surveys were performed. Patients received less than 6 months of glucocorticoids. Results. Of 351 transplant patients, 175 patients provided fracture information, with 48 (27.4%) having fractured since transplant (2–6 years). Transplants included 19 kidney/liver (50% male), 47 kidney/pancreas (53% male), 92 liver (65% male), and 17 pancreas transplants (41% male). Age at transplant was 50.8 ± 10.3 years. Fractures were equally seen across both genders and transplant types. Calcium supplementation (n = 94) and bisphosphonate therapy (n = 52) were observed, and an association with a lower risk of fractures was noted for bisphosphonate users (OR = 0.45 95% C.I. 0.24, 0.85). Fracture location included 8 (16.7%) foot, 12 (25.0%) vertebral, 3 (6.3%) hand, 2 (4.2%) humerus, 5 (10.4%) wrist, 10 (20.8%) fractures at other sites, and 7 (14.6%) multiple fractures. The estimated relative risk of fracture was nearly seventeen-times higher in male liver transplant recipients ages 45–64 years compared with the general male population, and comparable to fracture rates on conventional immunosuppressant regimens. Conclusion. We identify a high frequency of fractures in transplant recipients despite limited glucocorticoid use