Hydraulic acclimation in a Mediterranean oak subjected to permanent throughfall exclusion results in increased stem hydraulic capacitance

Stem water storage capacity and hydraulic capacitance (C_S) play a crucial role in tree survival under drought-stress. To investigate whether C_S adjusts to increasing water deficit, variation in stem water content (StWC) was monitored in vivo for 2 years and related to periodical measurements of tree water potential in Mediterranean Quercus ilex trees subjected either to permanent throughfall exclusion (TE) or to control conditions. Seasonal reductions in StWC were larger in TE trees relative to control ones, resulting in greater seasonal C_S (154 and 80 kg m⁻³ MPa⁻¹, respectively), but only during the first phase of the desorption curve, when predawn water potential was above −1.1 MPa. Below this point, C_S decreased substantially and did not differ between treatments (<20 kg m⁻³ MPa⁻¹). The allometric relationship between tree diameter and sapwood area, measured via electrical resistivity tomography, was not affected by TE. Our results suggest that (a) C_S response to water deficit in the drought-tolerant Q. ilex might be more important to optimize carbon gain during well-hydrated periods than to prevent drought-induced embolism formation during severe drought stress, and (b) enhanced C_S during early summer does not result from proportional increases in sapwood volume, but mostly from increased elastic water.     

QCT/FEA predictions of femoral stiffness are strongly affected by boundary condition modeling

Quantitative computed tomography-based finite element models of proximal femora must be validated with cadaveric experiments before using them to assess fracture risk in osteoporotic patients. During validation, it is essential to carefully assess whether the boundary condition (BC) modeling matches the experimental conditions. This study evaluated proximal femur stiffness results predicted by six different BC methods on a sample of 30 cadaveric femora and compared the predictions with experimental data. The average stiffness varied by 280% among the six BCs. Compared with experimental data, the predictions ranged from overestimating the average stiffness by 65% to underestimating it by 41%. In addition, we found that the BC that distributed the load to the contact surfaces similar to the expected contact mechanics predictions had the best agreement with experimental stiffness. We concluded that BC modeling introduced large variations in proximal femora stiffness predictions.     

Microscopic characterization reveals the diversity of EVs secreted by GFP-HAS3 expressing MCF7 cells

We have shown the connection of hyaluronan synthesis activity with the enhanced shedding of extracellular vesicles, but detailed morphological analysis of those hyaluronan-induced EVs is still missing. In this study we utilized a comprehensive set of high-resolution imaging techniques to characterize in high detail the size and morphology of EVs originating from stable MCF7 breast cancer cell line and transiently transfected cells expressing GFP-HAS3. To avoid possible artefacts or loss of EVs resulting from the isolation process, special attention was paid to analysis of EVs in situ in monolayer and in 3D cultures. The results of this study show that GFP-HAS3 expressing MCF7 cells produce morphologically diverse EVs but also demonstrates the variation in results obtained with different experimental setup, which emphasizes the importance of comparison between different methods when interpreting the observations.     

Rapid Stereoselective Hydrolysis of (+)-Cocaine in Baboon Plasma Prevents Its Uptake in the Brain: Implications for Behavioral Studies

The naturally occurring enantiomer of cocaine, (–)-cocaine, has been previously labeled with ¹¹C on the N-methyl group and used in conjunction with positron emission tomography to show that cocaine is rapidly taken up in the striata of human and baboon brain. In the present study, the behaviorally inactive (+)-cocaine was similarly labeled, with a view to its use for measuring the nonspecific binding of cocaine. No brain uptake was seen, although transport of cocaine into the brain is not expected to be stereoselective. The explanation for the lack of uptake was determined to be very rapid metabolism of (+)-cocaine in the blood. By 30s after administration of labeled (+)-cocaine, it was undetectable in plasma. In vitro studies demonstrated that (+)-cocaine is 50% debenzoylated to (+)-ecgonine methyl ester within 5 s of exposure to baboon plasma but not to washed erythrocytes. The hydrolysis of (–)-cocaine is at least 1,000 times slower. Serum butyrylcholinesterase (EC 3.1.1.8) appears to be responsible for this hydrolysis, as evidenced by its inhibition by physostigmine and catalysis by commercially available pseudocholinesterase from horse and human blood.     

Pharmacokinetic and pharmacodynamic studies of CD19 CAR T cell in human leukaemic xenograft models with dual-modality imaging

In recent years, chimeric antigen receptor T (CAR T)-cell therapy has shown great potential in treating haematologic disease, but no breakthrough has been achieved in solid tumours. In order to clarify the antitumour mechanism of CAR T cell in solid tumours, the pharmacokinetic (PK) and pharmacodynamic (PD) investigations of CD19 CAR T cell were performed in human leukaemic xenograft mouse models. For PK investigation, we radiolabelled CD19 CAR T cell with ⁸⁹Zr and used PET imaging in the CD19-positive and the CD19-negative K562-luc animal models. For PD evaluation, optical imaging, tumour volume measurement and DNA copy-number detection were performed. Unfortunately, the qPCR results of the DNA copy number in the blood were below the detection limit. The tumour-specific uptake was higher in the CD19-positive model than in the CD19-negative model, and this was consistent with the PD results. The preliminary PK and PD studies of CD19 CAR T cell in solid tumours are instructive. Considering the less efficiency of CAR T-cell therapy of solid tumours with the limited number of CAR T cells entering the interior of solid tumours, this study is suggestive for the subsequent CAR T-cell design and evaluation of solid tumour therapy.     

Metal complexes as optical probes for DNA sensing and imaging

Transition and lanthanide metal complexes have rich photophysical properties that can be used for cellular imaging, biosensing and phototherapy. One of the applications of such luminescent compounds is the detection and visualisation of nucleic acids. In this brief review, we survey the recent literature on the use of luminescent metal complexes (including Re^I, Ru^II, Os^II, Ir^III, Pt^II, Eu^III and Tb^III) as DNA optical probes, including examples of compounds that bind selectively to non-duplex DNA topologies such as quadruplex, i-motif and DNA mismatches. We discuss the applications of metal-based luminescent complexes in cellular imaging, including time-resolved microscopy and super-resolution techniques. Their applications in biosensing and phototherapy are briefly mentioned in the relevant sections.     

68Ga-DOTA and analogs: Current status and future perspectives

The construction of the ⁶⁸Ge/⁶⁸Ga generator has increased application of radiopharmaceuticals labeled with this isotope in medicine. ⁶⁸Ga-PET is widely employed in the management of neuroendocrine tumors but favorable chemistry with tri- and tetraaza-ring molecules has opened wide range of ⁶⁸Ga application in other fields of PET imaging. This review covers the radiopharmaceuticals labeled with gallium in molecular imaging and shows perspectives on the use of gallium-68 as a substitute for technetium-99, fluorine-18 and carbon-11 in some applications.     

Genetic trends of conformation traits and genetic correlations to osteochondrosis in boars

The objective of our study was to investigate the heritabilities and genetic correlations between traits from a linear exterior assessment system and osteochondrosis (OC) measured by computed tomography (CT), and in addition, to study the genetic trend in a population where the conformation traits have been included in the breeding goal. The data material consisted of phenotypes from a total of 4571 Norsvin Landrace test boars. At the end of the test period, all boars were subjected to a detailed exterior assessment system. Within 10 days of the assessment, the boars were CT scanned for measuring OC. The total score of osteochondrosis (OCT), used in this study, is the sum of phenotypes from the assessment on the medial and lateral condyles at the distal end of both the humerus and the femur of the right and the left leg of the boar based on images from CT. The exterior assessment traits included in the study were; ‘front leg knee’ (FKNE), ‘front leg pasterns’ (FPAS), ‘front leg stance’ (FSTA), ‘front leg twisted pasterns’ (FFLK), ‘hind leg stance’, ‘hind leg pasterns’ (HPAS), ‘hind leg standing under’ (HSTU), ‘hind leg small inner toe’, ‘dipped back’, ‘arched back’ (ARCH) and ‘waddling hindquarters’ (WADL). The estimation of (co)variance components and breeding values were performed using bivariate animal genetic models. Breeding values for HSTU, HPAS, FPAS, WADL and OCT traits were additional outputs from the same bivariate analyses. The lowest heritability was found for FFLK (h²_FFLK=0.05), whereas FPAS was estimated to have the highest heritability (h²_FPAS=0.36), and OCT demonstrating a heritability of 0.29. Significant genetic correlations were found between several traits; the strongest correlation was between FSTA and FFLK (0.94), which was followed by the correlation between FPAS and FKNE (0.69). The traits ARCH and FSTA had significant genetic correlations to OCT, whereas all other genetic correlations between OCT and the conformation traits were low and not significantly different from 0. Our study shows positive genetic trends for the conformation traits included in the breeding goal. In general, low genetic correlations between conformation traits and OC were observed in our study.