Induced pluripotent stem cell derived hepatocytes (IPSC-Heps) have the potential to reduce the demand for a dwindling number of primary cells used in applications ranging from therapeutic cell ...infusions to in vitro toxicology studies. However, current differentiation protocols and culture methods produce cells with reduced functionality and fetal-like properties compared to adult hepatocytes. We report a culture method for the maturation of IPSC-Heps using 3-Dimensional (3D) collagen matrices compatible with high throughput screening. This culture method significantly increases functional maturation of IPSC-Heps towards an adult phenotype when compared to conventional 2D systems. Additionally, this approach spontaneously results in the presence of polarized structures necessary for drug metabolism and improves functional longevity to over 75 days. Overall, this research reveals a method to shift the phenotype of existing IPSC-Heps towards primary adult hepatocytes allowing such cells to be a more relevant replacement for the current primary standard.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Numerous previous studies have constructed models to estimate base flow characteristics from climatic and physiographic characteristics of catchments and applied these to ungauged regions. However, ...these studies generally used streamflow observations from a relatively small number of catchments (<200) located in small, homogeneous study areas, which may have led to less reliable models with limited applicability elsewhere. Here, we use streamflow observations from a highly heterogeneous set of 3394 catchments (<10,000 km2) worldwide to construct reliable, widely applicable models based on 18 climatic and physiographic characteristics to estimate two important base flow characteristics: (1) the base flow index (BFI), defined as the ratio of long‐term mean base flow to total streamflow; and (2) the base flow recession constant (k), defined as the rate of base flow decay. Regression analysis results revealed that BFI and k were related to several climatic and physiographic characteristics, notably mean annual potential evaporation, mean snow water equivalent depth, and abundance of surface water bodies. Ensembles of artificial neural networks (ANNs; obtained by subsampling the original set of catchments) were trained to estimate the base flow characteristics from climatic and physiographic data. The catchment‐scale estimation of the base flow characteristics demonstrated encouraging performance with R2 values of 0.82 for BFI and 0.72 for k. The connection weights of the trained ANNs indicated that climatic characteristics were more important for estimating k than BFI. Global maps of estimated BFI and k were obtained using global climatic and physiographic data as input to the derived models. The resulting global maps are available for free download at http://www.hydrology-amsterdam.nl.
Key Points
We trained neural networks to estimate baseflow index and recession rate
Streamflow observations from 3394 catchments were used for the training
First global maps of baseflow index and recession rate
Chronic obstructive pulmonary disease (COPD) is the third commonest cause of death globally, and manifests as a progressive inflammatory lung disease with no curative treatment. The lung microbiome ...contributes to COPD progression, but the function of the gut microbiome remains unclear. Here we examine the faecal microbiome and metabolome of COPD patients and healthy controls, finding 146 bacterial species differing between the two groups. Several species, including Streptococcus sp000187445, Streptococcus vestibularis and multiple members of the family Lachnospiraceae, also correlate with reduced lung function. Untargeted metabolomics identifies a COPD signature comprising 46% lipid, 20% xenobiotic and 20% amino acid related metabolites. Furthermore, we describe a disease-associated network connecting Streptococcus parasanguinis_B with COPD-associated metabolites, including N-acetylglutamate and its analogue N-carbamoylglutamate. While correlative, our results suggest that the faecal microbiome and metabolome of COPD patients are distinct from those of healthy individuals, and may thus aid in the search for biomarkers for COPD.
Fluorination of conjugated molecules has been established as an effective structural modification strategy to influence properties and has attracted extensive attention in organic solar cells (OSCs). ...Here, we have investigated optoelectronic and photovoltaic property changes of OSCs made of polymer donors with the non-fullerene acceptors (NFAs) ITIC and IEICO and their fluorinated counterparts IT-4F and IEICO-4F. Device studies show that fluorinated NFAs lead to reduced V oc but increased J sc and fill-factor (FF), and therefore, the ultimate influence to efficiency depends on the compensation of V oc loss and gains of J sc and FF. Fluorination lowers energy levels of NFAs, reduces their electronic band gaps, and red-shifts the absorption spectra. The impact of fluorination on the molecular order depends on the specific NFA, and the conversion of ITIC to IT-4F reduces the structural order, which can be reversed after blending with the donor PBDB-T. Contrastingly, IEICO-4F presents stronger π–π stacking after fluorination from IEICO, and this is further strengthened after blending with the donor PTB7-Th. The photovoltaic blends universally present a donor-rich surface region which can promote charge transport and collection toward the anode in inverted OSCs. The fluorination of NFAs, however, reduces the fraction of donors in this donor-rich region, consequently encouraging the intermixing of donor/acceptor for efficient charge generation.
Increasing incidence of inflammatory bowel diseases, such as Crohn's disease, in developed nations is associated with changes to the microbial environment, such as decreased prevalence of helminth ...colonization and alterations to the gut microbiota. We find that helminth infection protects mice deficient in the Crohn's disease susceptibility gene Nod2 from intestinal abnormalities by inhibiting colonization by an inflammatory Bacteroides species. Resistance to Bacteroides colonization was dependent on type 2 immunity, which promoted the establishment of a protective microbiota enriched in Clostridiales. Additionally, we show that individuals from helminth-endemic regions harbor a similar protective microbiota and that deworming treatment reduced levels of Clostridiales and increased Bacteroidales. These results support a model of the hygiene hypothesis in which certain individuals are genetically susceptible to the consequences of a changing microbial environment.
Key questions in COVID-19 are the duration and determinants of infectious virus shedding. Here, we report that infectious virus shedding is detected by virus cultures in 23 of the 129 patients ...(17.8%) hospitalized with COVID-19. The median duration of shedding infectious virus is 8 days post onset of symptoms (IQR 5-11) and drops below 5% after 15.2 days post onset of symptoms (95% confidence interval (CI) 13.4-17.2). Multivariate analyses identify viral loads above 7 log
RNA copies/mL (odds ratio OR of 14.7 (CI 3.57-58.1; p < 0.001) as independently associated with isolation of infectious SARS-CoV-2 from the respiratory tract. A serum neutralizing antibody titre of at least 1:20 (OR of 0.01 (CI 0.003-0.08; p < 0.001) is independently associated with non-infectious SARS-CoV-2. We conclude that quantitative viral RNA load assays and serological assays could be used in test-based strategies to discontinue or de-escalate infection prevention and control precautions.
Quantum dot (QD) solids are an emerging platform for developing a range of optoelectronic devices. Thus, understanding exciton dynamics is essential towards developing and optimizing QD devices. ...Here, using transient absorption microscopy, we reveal the initial exciton dynamics in QDs with femtosecond timescales. We observe high exciton diffusivity (~10
cm
s
) in lead chalcogenide QDs within the first few hundred femtoseconds after photoexcitation followed by a transition to a slower regime (~10
-1 cm
s
). QD solids with larger interdot distances exhibit higher initial diffusivity and a delayed transition to the slower regime, while higher QD packing density and heterogeneity accelerate this transition. The fast transport regime occurs only in materials with exciton Bohr radii much larger than the QD sizes, suggesting the transport of delocalized excitons in this regime and a transition to slower transport governed by exciton localization. These findings suggest routes to control the optoelectronic properties of QD solids.
Nanocrystal quantum dots are generally coated with an organic ligand layer. These layers are a necessary consequence of their chemical synthesis, and in addition they play a key role in controlling ...the optical and electronic properties of the system. Here we describe a method for quantitative measurement of the ligand layer in 3 nm diameter lead sulfide–oleic acid quantum dots. Complementary small-angle X-ray and neutron scattering (SAXS and SANS) studies give a complete and quantitative picture of the nanoparticle structure. We find greater-than-monolayer coverage of oleic acid and a significant proportion of ligand remaining in solution, and we demonstrate reversible thermal cycling of the oleic acid coverage. We outline the effectiveness of simple purification procedures with applications in preparing dots for efficient ligand exchange. Our method is transferrable to a wide range of colloidal nanocrystals and ligand chemistries, providing the quantitative means to enable the rational design of ligand-exchange procedures.
The phylogenetic composition of the heterotrophic microbial community is depth stratified in the oceanic water column down to abyssopelagic layers. In the layers below the euphotic zone, it has been ...suggested that heterotrophic microbes rely largely on solubilized particulate organic matter as a carbon and energy source rather than on dissolved organic matter. To decipher whether changes in the phylogenetic composition with depth are reflected in changes in the bacterial and archaeal transporter proteins, we generated an extensive metaproteomic and metagenomic dataset of microbial communities collected from 100- to 5,000-m depth in the Atlantic Ocean. By identifying which compounds of the organic matter pool are absorbed, transported, and incorporated into microbial cells, intriguing insights into organic matter transformation in the deep ocean emerged. On average, solute transporters accounted for 23% of identified protein sequences in the lower euphotic and ∼39% in the bathypelagic layer, indicating the central role of heterotrophy in the dark ocean. In the bathypelagic layer, substrate affinities of expressed transporters suggest that, in addition to amino acids, peptides and carbohydrates, carboxylic acids and compatible solutes may be essential substrates for themicrobial community. Key players with highest expression of solute transporters were Alphaproteobacteria, Gammaproteobacteria, and Deltaproteobacteria, accounting for 40%, 11%, and 10%, respectively, of relative protein abundances. The in situ expression of solute transporters indicates that the heterotrophic prokaryotic community is geared toward the utilization of similar organic compounds throughout the water column, with yet higher abundances of transporters targeting aromatic compounds in the bathypelagic realm.
We present N-body simulations of planetary system formation in thermally evolving, viscous disc models. The simulations incorporate type I migration (including corotation torques and their ...saturation), gap formation, type II migration, gas accretion on to planetary cores and gas disc dispersal through photoevaporation. The aim is to examine whether or not the oligarchic growth scenario, when combined with self-consistent disc models and up-to-date prescriptions for disc-driven migration, can produce planetary systems similar to those that have been observed. The results correlate with the initial disc mass. Low-mass discs form close-packed systems of terrestrial-mass planets and super-Earths. Higher mass discs form multiple generations of planets, with masses in the range 10 ≲ m
p ≲ 45 M⊕. These planets generally type I migrate into the inner disc, because of corotation torque saturation, where they open gaps and type II migrate into the central star. Occasionally, a final generation of low- to intermediate-mass planets forms and survives due to gas disc dispersal. No surviving gas giants were formed in our simulations. Analysis shows that these planets can only survive migration if a core forms and experiences runaway gas accretion at orbital radii r ≳ 10 au prior to the onset of type II migration. We conclude that planet growth above masses m
p ≳ 10 M⊕ during the gas disc lifetime leads to corotation torque saturation and rapid inward migration, preventing the formation and survival of gas giants. This result is in contrast to the success in forming gas giant planets displayed by some population synthesis models. This discrepancy arises, in part, because the type II migration prescription adopted in the population synthesis models causes too large a reduction in the migration speed when in the planet-dominated regime.
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