Deciphering the SUMO code in the kidney

SUMOylation of proteins is an important regulatory element in modulating protein function and has been implicated in the pathogenesis of numerous human diseases such as cancers, neurodegenerative diseases, brain injuries, diabetes, and familial dilated cardiomyopathy. Growing evidence has pointed to a significant role of SUMO in kidney diseases such as DN, RCC, nephritis, AKI, hypertonic stress and nephrolithiasis. Recently, emerging studies in podocytes demonstrated that SUMO might have a protective role against podocyte apoptosis. However, the SUMO code responsible for beneficial outcome in the kidney remains to be decrypted. Our recent experiments have revealed that the expression of both SUMO and SUMOylated proteins is appreciably elevated in hypoxia‐induced tubular epithelial cells (TECs) as well as in the unilateral ureteric obstruction (UUO) mouse model, suggesting a role of SUMO in TECs injury and renal fibrosis. In this review, we attempt to decipher the SUMO code in the development of kidney diseases by summarizing the defined function of SUMO and looking forward to the potential role of SUMO in kidney diseases, especially in the pathology of renal fibrosis and CKD, with the goal of developing strategies that maximize correct interpretation in clinical therapy and prognosis.     

Variation of phenotype,ploidy level,and organogenic potential of in vitro regenerated polyploids of <Emphasis Type=Italic>Pyrus communis</Emphasis>

A wide range of phenotypic variation was observed among neopolyploids obtained from the diploid pear cultivar ‘Fertility’ by in vitro colchicine treatment. The variant plantlets had alterations in leaf characteristics. Neopolyploids had significantly different ratios of leaf length to leaf width compared to the diploid control. Shoot regeneration from leaf explants and rooting ability from in vitro shoots of neopolyploids was examined. Regeneration frequencies of shoots from leaf explants of seven of the nine neopolyploids were significantly decreased compared to the diploid control. The organogenic potential of neopolyploids was highly genotype-dependent for both shoots and roots. Tetraploid clone 4x − 4 failed to regenerate shoots from leaf explants and the pentaploid clone 5x − 2 failed to root from in vitro shoots. The results suggest that polyploidization caused the decrease in or loss of in vitro organogenic potential. Regenerated shoots derived from neopolyploids showed different phenotypes, depending on the ploidy of the donor plant.     

Establishment of Transfer Functions of the Pollen-Climatic Factors in Northern China and the Quantitative Climatic Reconstruction at DJ Core

The 2.4 meter-long core was extracted from the Diaojiao lake (41º18′N, 112º21′E) at the foot of the northern part of Daqingshan Mts. Pollen analysis from collections subsampled in the laboratory at 2 cm intervals, revealed plentiful pollen and spores from over 10 arboreal genera, including Pinus, Betula, Picea, Abies, Carpinus, Quercus, Ulmus and more than 20 non-arboreal genera, mainly of Artemisia, Labiatae, Nitraria, Polygonaceae, Ranunculus, Thalictrum, Umbel- liferae, Caryophyllaceae and Cyperaceae. Fern spores, aquatic pollen and algae were also observed in some parts of the core. The transfer functions were established by the stepwise regression analysis using the climatic factors and 13 pollen taxa. The different Fl and F2 value were used as the thresh- old value of F test (i. e. used for selecting and deleting factors). Each regressed equation was obtained from 70 times of calculations with a step-wise increase of 0.1 for Fl and F2 and those having the smallest regression deviation and the largest multiple correlation coefficient were the final four transfer functions. Substituting the pre-factor obtained from the stratigraphic sampled into the regression equations, the estimates of temperature and precipitation in January and in July, and annual mean temperature values could be calculated. Some climatic stages were inferred from total pollen influx and pollen percentage from the core using a transfer function: humid-cool (from 10 000 to 7 800 a BP), arid-cold (9 200 to 7 900 a BP), arid-warm (7 900 to 7 100 a BP), humid-warm (7 100 to 4 400 a BP), arid-warm (4 400 to 3 000 a BP), arid-cold (3 000 to 2 100 a BP). The highest annual mean temperature during Holocene was ca. 4 ℃ higher and the lowest was ca. 2 ℃ lower than the present temperature. Annual precipitation was 250 mm higher and 300 mm lower than the present.     

Maintenance of CMV-specific CD8+ T cell responses and the relationship of IL-27 to IFN-γ levels with aging

We investigated whether healthy young (age ? 40) and elderly (age ? 65) people infected with cytomegalovirus (CMV) had similar levels of CD8⁺ T cell cytokine production and proliferation in response to an immunodominant CMV pp65 peptide pool given the role of CD8⁺ T cells in controlling viral infection and the association of CMV with immunosenescence. Plus, we determined the effects of aging and CMV-infectious status on plasma levels of IL-27, an innate immune cytokine with pro- and anti-inflammatory properties, as well as on its relationship to IFN-γ in that IL-27 can promote the production of IFN-γ. The results of our study show that young and elderly people had similar levels of CD8⁺ T cell proliferation, and IFN-γ and TNF-α production in response to CMV pp65 peptides. Plasma levels of IL-27 were similar between the two groups although CMV-infected young and elderly people had a trend toward increased levels of IL-27. Regardless of aging and CMV-infectious status, plasma levels of IL-27 correlated highly with plasma levels of IFN-γ. These findings suggest the maintenance of CMV pp65-specific CD8⁺ T cell proliferation and cytokine production with aging as well as the sustaining of circulatory IL-27 levels and its biological link to IFN-γ in young and elderly people irrespective of CMV infection.     

Efficiency Boost in All-Small-Molecule Organic Solar Cells: Insights from the Re-Ordering Kinetics

Achieving high-performance in all-small-molecule organic solar cells (ASM-OSCs) significantly relies on precise nanoscale phase separation through domain size manipulation in the active layer. Nonetheless, for ASM-OSC systems, forging a clear connection between the tuning of domain size and the intricacies of phase separation proves to be a formidable challenge. This study investigates the intricate interplay between domain size adjustment and the creation of optimal phase separation morphology, crucial for ASM-OSCs’ performance. It is demonstrated that exceptional phase separation in ASM-OSCs’ active layer is achieved by meticulously controlling the continuity and uniformity of domains via re-packing process. A series of halogen-substituted solvents (Fluorobenzene, Chlorobenzene, Bromobenzene, and Iodobenzene) is adopted to tune the re-packing kinetics, the ASM-OSCs treated with CB exhibited an impressive 16.2% power conversion efficiency (PCE). The PCE enhancement can be attributed to the gradual crystallization process, promoting a smoothly interconnected and uniformly distributed domain size. This, in turn, leads to a favorable phase separation morphology, enhanced charge transfer, extended carrier lifetime, and consequently, reduced recombination of free charges. The findings emphasize the pivotal role of re-packing kinetics in achieving optimal phase separation in ASM-OSCs, offering valuable insights for designing high-performance ASM-OSCs fabrication strategies.     

Use of moving aeration membrane bioreactor for the efficient production of tissue type plasminogen activator in serum free medium

A moving aeration-membrane (MAM) bioreactor was employed for the production of 2 μg/mL of tissue type Plasminogen Activator (tPA) in serum free medium from normal human fibroblast cells. This system could maintain high cell density for long periods of steady state conditions in perfusion cultivation. Under normal operating conditions, shear stress was as low as 0.65 dynes/cm² at the agitation speed of 80 rpm. Even though cell density gradually decreased with increasing agitation speed, tPA production increased linearly with increasing shear stress within a moderate range. This culture system allowed production of 2 μg tPA/mL while maintaining a high cell density of 1.0×10⁷ viable cells/mL.     

In Vivo Orientation of Single Myosin Lever Arms in Zebrafish Skeletal Muscle

Cardiac and skeletal myosin assembled in the muscle lattice power contraction by transducing ATP free energy into the mechanical work of moving actin. Myosin catalytic/lever-arm domains comprise the transduction/mechanical coupling machinery that move actin by lever-arm rotation. In vivo, myosin is crowded and constrained by the fiber lattice as side chains are mutated and otherwise modified under normal, diseased, or aging conditions that collectively define the native myosin environment. Single-myosin detection uniquely defines bottom-up characterization of myosin functionality. The marriage of in vivo and single-myosin detection to study zebrafish embryo models of human muscle disease is a multiscaled technology that allows one-to-one registration of a selected myosin molecular alteration with muscle filament-sarcomere-cell-fiber-tissue-organ- and organism level phenotypes. In vivo single-myosin lever-arm orientation was observed at superresolution using a photoactivatable-green-fluorescent-protein (PAGFP)-tagged myosin light chain expressed in zebrafish skeletal muscle. By simultaneous observation of multiphoton excitation fluorescence emission and second harmonic generation from myosin, we demonstrated tag specificity for the lever arm. Single-molecule detection used highly inclined parallel beam illumination and was verified by quantized photoactivation and photobleaching. Single-molecule emission patterns from relaxed muscle in vivo provided extensive superresolved dipole orientation constraints that were modeled using docking scenarios generated for the myosin (S1) and GFP crystal structures. The dipole orientation data provided sufficient constraints to estimate S1/GFP coordination. The S1/GFP coordination in vivo is rigid and the lever-arm orientation distribution is well-ordered in relaxed muscle. For comparison, single myosins in relaxed permeabilized porcine papillary muscle fibers indicated slightly differently oriented lever arms and rigid S1/GFP coordination. Lever arms in both muscles indicated one preferred spherical polar orientation and widely distributed azimuthal orientations relative to the fiber symmetry axis. Cardiac myosin is more radially displaced from the fiber axis. Probe rigidity implies the PAGFP tag reliably indicates cross-bridge orientation in situ and in vivo.