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The life stories can constitute more than simple biographies to remain great lessons of honesty, grit and steadfastness in keeping standards of medical science within a strong moral fiber and flexible wiseness in hard terms like in case of Zygmunt Albert (1908-2001). This eminent pathologist histochemically visualized tissue distribution of gamma-glutamyl transpeptidase in liver and other organs under various conditions. He was also deeply involved in experimental pathology of liver, particularly in his comprehensive studies on chrysoidin-induced hepatoma that should bear eponymic name Albert's hepatoma. As he had both German and Polish roots, he became an eminent personage that wisely and consequently bridged neighboring civilizations in hard terms of escalation of hate in prewar times, during World War II and in postwar period. After he meticulously recorded Nazi crimes in Lvov, he appealed for justice in case of Nazi massive murders of Lvov Professors. He obtained his Associate Professorship in Anatomical Pathology in Lvov (Lemberg) and was one of rebuilders of Medical Faculty in postwar Wrocław (Breslau) to serve as the first Rector Magnificus of Medical Academy of Wrocław.
Powdery mildew is a persistent disease affecting the cultivation of Rosa, a genus of substantial horticultural and economic value worldwide. Despite more than a century of study, the true diversity of powdery mildews infecting roses has remained unclear, largely due to the long-standing and overly broad application of the name Podosphaera pannosa. To reassess this system, we conducted an extensive investigation of powdery mildew specimens infecting Rosa. A total of 112 collections were examined, including recently gathered material from 23 provinces, historical types, representative specimens from the Herbarium Mycologicum Academiae Sinicae (HMAS), China, and a neotype specimen from Germany. Morphological observations combined with phylogenetic analyses (ITS, 28S, and IGS rDNA) resolved several long-standing taxonomic problems and revealed unexpected diversity within the rose powdery mildew complex. Molecular data from Erysiphe rosae provide the first phylogenetic evidence supporting the synonymy of Medusosphaera with Erysiphe. Sphaerotheca rosae, previously treated as a synonym of P. pannosa, is reinstated as a distinct species as Podosphaera rosae comb. nov., and a previously unrecognized lineage is described as Podosphaera rosae-xanthinae sp. nov. In addition, earlier varieties of E. simulans are shown to lack diagnostic morphological or genetic characters and are no longer supported. Taken together, these results demonstrate that powdery mildews on Rosa represent a complex of five species across two genera, structured by host phylogeny. Clear patterns of host preference and distribution indicate a history of co-evolution and ecological differentiation driven by host availability. This study fundamentally revises our understanding of rose powdery mildews, revealing a level of taxonomic and evolutionary complexity much greater than previously recognized and highlighting Rosa as a key host lineage in the diversification of the Erysiphaceae.
The Trichiaceae, a major family of Myxomycetes, has undergone significant taxonomic revision in recent years. Yet, systematic research on this group in China remains limited, resulting in outdated taxonomy and persistent gaps in species diversity and biogeographic understanding. To resolve this, this study performed a comprehensive revision of Chinese Trichiaceae, combining morphological analysis (light and scanning electron microscopy) and multigene phylogenetics (nuclear 18S rDNA, elongation factor-1 alpha, and mitochondrial small subunit ribosomal RNA) based on specimens deposited in the Herbarium of Fungi at Nanjing Normal University and the Herbarium Mycologicum, Academiae Sinicae. We also synthesized published literature to compile an updated checklist of 65 species with detailed Chinese distribution records. This study describes two new species (Metatrichia scintillans and Trichia coronata), revises one species (Oligonema latitubulare), and reports four new records for China (Ophiotheca calongei, Trichia acetocorticola, Trichia pinicola, and Trichia taeniifila). This study addresses key knowledge gaps in China's myxomycete biota and provides a standardized framework for future research on Trichiaceae biodiversity and taxonomy.
Fibroblast growth factor 1 (FGF1), a well-characterized member of the FGF family, effectively lowers blood glucose levels in animal models of type 2 diabetes by stimulating glucose uptake. However, its significant mitogenic potential poses a major challenge for clinical application. Here, we present engineered variants of FGF1 designed to dissociate its potent glucose-lowering effects from its undesired proliferative activity, aiming for a future therapeutic agent for type 2 diabetes. Through a series of rational mutations focused on modulating receptor binding and heparan interactions, coupled with enhanced thermodynamic stability, we developed two lead FGF1 variants. Comprehensive in vitro studies confirmed that these variants exhibit significantly reduced mitogenic potential across various cell types compared to wild-type FGF1. Specifically, one variant showed profound loss of proliferation due to disrupted FGFR binding, while the other displayed attenuated mitogenicity linked to decreased heparin affinity. Critically, both fully maintained potent glucose-lowering properties in db/db mice without inducing hypoglycemia or changes in body weight. Furthermore, these engineered proteins demonstrate superior thermodynamic stability and markedly improved pharmacokinetic profile, critical attributes for drug development. Our findings highlight a successful strategy to uncouple the therapeutic benefits of FGF1 from its mitogenic side effects, offering promising, stable, and safe protein-based drug candidates for type 2 diabetes treatment.
Electrical stimuli play a crucial role in activating cell signaling pathways and promoting essential functions such as migration, proliferation, and differentiation, while also enabling communication between specific cell types. Bioelectronics aims to modulate the biological activity of living tissues and organs through minimally invasive electrical stimulation. This work aims to develop and validate cytocompatible, subcellular-sized wireless microdevices fabricated through a scalable silicon microtechnology process. These microdevices consist of a micrometer-scale silicon dioxide platform integrating ZnO nanosheets (NSs) as the active piezoelectric material. They establish electromechanical interactions with cells, driven by intrinsic cellular forces or by external ultrasound actuation in the biomedical range. This study demonstrates the underpinning mechanism of this electromechanical interaction. Mechanical forces, whether generated intrinsically by cells or applied through ultrasound, deform the nanostructures and generate localized piezopotentials that depolarize the membrane and trigger calcium transients. Pharmacological studies revealed that calcium entry occurs mainly through voltage-gated calcium channels (VGCCs) and stretch-activated cation channels (SACCs), with a minor contribution from intracellular stores. Membrane potential imaging confirmed dynamic depolarization events, validating direct cell-nanogenerator coupling. Ultrasound actuation further enhanced the effect, with 58% of cells activated, underscoring the promise of piezoelectric nanogenerators for minimally invasive cellular-level bioelectronic interfaces and biomedical applications.
Variational Quantum Algorithms (VQAs) provide a promising framework for solving electronic structure problems using the computational capabilities of quantum computers to explore high-dimensional Hilbert spaces efficiently. This research investigates the performance of VQAs in electronic structure calculations of gallium arsenide (GaAs), a semiconductor with a zinc-blende structure. Utilizing a tight-binding Hamiltonian and a Jordan-Wigner-like transformation, we map the problem to a 10-qubit Hamiltonian. We analyze the impact of quantum circuit architectures, algorithm hyperparameters, and optimization methods on two VQAs: Variational Quantum Deflation (VQD) and Subspace Search Variational Quantum Eigensolver (SSVQE). We observed that while both algorithms offer promising results, the choice of ansatz and hyperparameter tuning were especially critical in achieving reliable outcomes, particularly for higher energy states. Adjusting the hyperparameters in VQD significantly enhanced the accuracy of higher energy state calculations, reducing the error by an order of magnitude, whereas tuning the hyperparameters in SSVQE had minimal impact. Our findings provide insights into optimizing VQAs for electronic structure problems, paving the way for their application to more complex systems on near-term quantum devices.
Modern tissue engineering requires not only degradable materials promoting cell growth and differentiation, but also vascularization of the engineered tissue. Porous polylactide/polycaprolactone (PLA/PCL, ratio 3/5) foam scaffolds were prepared by a combined porogen leaching and freeze-drying technique using NaCl (crystal size 250-500 µm) and a water-soluble cellulose derivative (KlucelTM E; 10-100% w/w relative to the total PLA/PCL concentration) as porogens. Scanning electron microscopy, micro-CT, and Brunauer-Emmett-Teller analysis showed that all scaffolds contained a trimodal range of pore sizes, i.e., macropores (average diameter 298-539 μm), micropores (100 nm to 10 μm), and nanopores (mostly around 3.0 nm). All scaffolds had an open porosity of about 90%, and the pores were interconnected. The size of the macropores and the nanoporosity were higher in the scaffolds prepared with Klucel. Nanoporosity increased water uptake by the scaffolds, while macroporosity promoted cell ingrowth, which was most evident in scaffolds prepared with 25% Klucel. Human adipose-derived stem cells co-cultured with endothelial cells formed pre-vascular structures in the scaffolds, which was further enhanced in a dynamic cell culture system. The scaffolds are promising for the engineering of pre-vascularized soft tissues (relatively pliable 10% Klucel scaffolds) and hard tissues (mechanically stronger 25% and 50% Klucel scaffolds).
Cell communication systems based on polypeptide ligands use transmembrane receptors to transmit signals across the plasma membrane. In their biogenesis, receptors depend on the endoplasmic reticulum (ER)-Golgi system for folding, maturation, transport and localization to the cell surface. ER stress, caused by protein overproduction and misfolding, is a well-known pathology in neurodegeneration, cancer and numerous other diseases. How ER stress affects cell communication via transmembrane receptors is largely unknown. In disease models of multiple myeloma, chronic lymphocytic leukemia and osteogenesis imperfecta, we show that ER stress leads to loss of the mature transmembrane receptors FGFR3, ROR1, FGFR1, LRP6, FZD5 and PTH1R at the cell surface, resulting in impaired downstream signaling. This is caused by downregulation of receptor production and increased intracellular retention of immature receptor forms. Reduction of ER stress by treatment of cells with the chemical chaperone tauroursodeoxycholic acid or by expression of the chaperone protein BiP resulted in restoration of receptor maturation and signaling. We show a previously unappreciated pathological effect of ER stress; impaired cellular communication due to altered receptor processing. Our findings have implications for disease mechanisms related to ER stress and are particularly important when receptor-based pharmacological approaches are used for treatment.
Perennial herbs of seasonal climates invest carbon into belowground storage organs (e.g. rhizomes) to support growth when photosynthetic acquisition cannot cover demands. An alternative explanation interprets storage allocation as surplus carbon that is undeployable for growth when plants are limited by nutrients/water. We analysed relative investments to rhizomes to see to which of these explanations they align, and asked whether they scale with biomass of aboveground organs in individual species and whether clonal growth traits, phenology or environmental conditions explain investment among populations or species. We measured biomass of rhizomes, aboveground stems and leaves in 20 temperate herbaceous perennial species, each at two localities, establishing allometric relationships for pairs of organs. We correlated relative rhizome investment with clonal traits, environmental gradients and phenology, across species. For pairs of organs, biomass typically scales isometrically. Interspecific allocation differences are largely explained by phenology. Neither interspecific nor intraspecific differences were explained by clonal traits or environment. Storage organs of perennial herbs do not comprise deposition of carbon surplus, but receive greater allocation in capital breeders (early-flowering), than among income breeders (late-flowering) relying on acquisition during growing season. Capital and income breeders in plants deserve further examination of benefits/costs.
Protein synthesis plays a major role in homeostasis and when dysregulated leads to various pathologies including cancer. To this end, imbalanced expression of eukaryotic translation initiation factors (eIFs) is not only a consequence but also a driver of neoplastic growth. eIF3 is the largest, multi-subunit translation initiation complex with a modular assembly, where aberrant expression of one subunit generates only partially functional subcomplexes. To comprehensively study the effects of eIF3 remodeling, we contrasted the impact of eIF3d, eIF3e or eIF3h depletion on the translatome of HeLa cells using Ribo-seq. Depletion of eIF3d or eIF3e, but not eIF3h reduced the levels of multiple components of the MAPK signaling pathways. Surprisingly, however, depletion of all three eIF3 subunits increased MAPK/ERK pathway activity. Depletion of eIF3e and partially eIF3d also increased translation of TOP mRNAs that encode mainly ribosomal proteins and other components of the translational machinery. Moreover, alterations in eIF3 subunit stoichiometry were often associated with changes in translation of mRNAs containing short uORFs, as in the case of the proto-oncogene MDM2 and the transcription factor ATF4. Collectively, perturbations in eIF3 subunit stoichiometry exert specific effect on the translatome comprising signaling and stress-related transcripts with complex 5' UTRs that are implicated in homeostatic adaptation to stress and cancer.
Syncytin-1, a human fusogenic protein of retroviral origin, is crucial for placental syncytiotrophoblast formation. To mediate cell-to-cell fusion, Syncytin-1 requires specific interaction with its cognate receptor. Two trimeric transmembrane proteins, Alanine, Serine, Cysteine Transporters 1 and 2 (ASCT1 and ASCT2), were suggested and widely accepted as Syncytin-1 cellular receptors. To quantitatively assess the individual contributions of human ASCT1 and ASCT2 to the fusogenic activity of Syncytin-1, we developed a model system where the ASCT1 and ASCT2 double knockout was rescued by ectopic expression of either ASCT1 or ASCT2. We demonstrated that ASCT2 was required for Syncytin-1 binding, cellular entry, and cell-to-cell fusion, while ASCT1 was not involved in this receptor interaction. We experimentally validated the ASCT1-ASCT2 heterotrimers as a possible explanation for the previous misidentification of ASCT1 as a receptor for Syncytin-1. This redefinition of receptor specificity is important for proper understanding of Syncytin-1 function in normal and pathological pregnancy.
Retroviruses integrate into the genomes of infected host cells to form proviruses, a genetic platform for stable viral gene expression. Epigenetic silencing can, however, hamper proviral transcriptional activity. As gammaretroviruses (γRVs) preferentially integrate into active promoter and enhancer sites, the high transcriptional activity of γRVs can be attributed to this integration preference. In addition, long terminal repeats (LTRs) of some γRVs were shown to act as potent promoters by themselves. Here, we investigate the capacity of different γRV LTRs to drive stable expression within a non-preferred epigenomic environment in the context of diverse retroviral vectors. We demonstrate that different γRV LTRs are either rapidly silenced or remain active for long periods of time with a predominantly active proviral population under normal and retargeted integration. As an alternative to the established γRV systems, the feline leukemia virus and koala retrovirus LTRs are able to drive stable, albeit intensity-diverse, transgene expression. Overall, we show that despite the occurrence of rapid silencing events, most γRV LTRs can drive stable expression outside of their preferred chromatin landscape after retrovirus integrations.
Diamond-like carbon (DLC) layers are known for their high corrosion and wear resistance, low friction, and high biocompatibility. However, it is often necessary to dope DLC layers with additional chemical elements to strengthen their adhesion to the substrate. Ti-DLC layers (doped with 0.4, 2.1, 3.7, 6.6, and 12.8 at.% of Ti) were prepared by dual pulsed laser deposition, and pure DLC, glass, and polystyrene (PS) were used as controls. In vitro cell-material interactions were investigated with an emphasis on cell adhesion, proliferation, and osteogenic differentiation. We observed slightly increasing roughness and contact angle and decreasing surface free energy on Ti-DLC layers with increasing Ti content. Three-week biological experiments were performed using adipose tissue-derived stem cells (ADSCs) and bone marrow mesenchymal stem cells (bmMSCs) in vitro. The cell proliferation activity was similar or slightly higher on the Ti-doped materials than on glass and PS. Osteogenic cell differentiation on all materials was proved by collagen and osteocalcin production, ALP activity, and Ca deposition. The bmMSCs exhibited greater initial proliferation potential and an earlier onset of osteogenic differentiation than the ADSCs. The ADSCs showed a slightly higher formation of focal adhesions, higher metabolic activity, and Ca deposition with increasing Ti content.
The detection sensitivity of secondary electrospray ionisation mass spectrometry (SESI-MS) is much lower for saturated aldehydes than for unsaturated aldehydes. This needs to be understood in terms of gas phase ion-molecule reaction kinetics and energetics to make SESI-MS analytically more quantitative. Parallel SESI-MS and selected ion flow tube mass spectrometry (SIFT-MS) analyses were carried out of air containing variable accurately determined concentrations of saturated (C5, pentanal; C7, heptanal; C8 octanal) and unsaturated (C5, 2-pentenal; C7, 2-heptenal; C8, 2-octenal) aldehyde vapours. The influence of the source gas humidity and the ion transfer capillary temperature, 250 and 300°C, in a commercial SESI-MS instrument was explored. Separate experiments were carried out using SIFT to determine the rate coefficients, k73 , for the ligand-switching reactions of the H3 O+ (H2 O)3 ions with the six aldehydes. The relative slopes of the plots of SESI-MS ion signal against SIFT-MS concentration were interpreted as the relative SESI-MS sensitivities for these six compounds. The sensitivities for the unsaturated aldehydes were 20 to 60 times greater than for the corresponding C5, C7 and C8 saturated aldehydes. Additionally, the SIFT experiments revealed that the measured k73 are three or four times greater for the unsaturated than for the saturated aldehydes. The trends in SESI-MS sensitivities are rationally explained by differences in the rates of the ligand-switching reactions, which are justified by theoretically calculated equilibrium rate constants derived from thermochemical density functional theory (DFT) calculations of Gibb's free energy changes. The humidity of SESI gas thus favours the reverse reactions of the saturated aldehyde analyte ions, effectively suppressing their signals in contrast to their unsaturated counterparts.
One of the major goals of vascular tissue engineering is to develop much-needed materials that are suitable for use in small-diameter vascular grafts. Poly(1,8-octamethylene citrate) can be considered for manufacturing small blood vessel substitutes, as recent studies have demonstrated that this material is cytocompatible with adipose tissue-derived stem cells (ASCs) and favors their adhesion and viability. The work presented here is focused on modifying this polymer with glutathione (GSH) in order to provide it with antioxidant properties, which are believed to reduce oxidative stress in blood vessels. Cross-linked poly(1,8-octamethylene citrate) (cPOC) was therefore prepared by polycondensation of citric acid and 1,8-octanediol at a 2:3 molar ratio of the reagents, followed by in-bulk modification with 0.4, 0.8, 4 or 8 wt.% of GSH and curing at 80 °C for 10 days. The chemical structure of the obtained samples was examined by FTIR-ATR spectroscopy, which confirmed the presence of GSH in the modified cPOC. The addition of GSH increased the water drop contact angle of the material surface and lowered the surface free energy values. The cytocompatibility of the modified cPOC was evaluated in direct contact with vascular smooth-muscle cells (VSMCs) and ASCs. The cell number, the cell spreading area and the cell aspect ratio were measured. The antioxidant potential of GSH-modified cPOC was measured by a free radical scavenging assay. The results of our investigation indicate the potential of cPOC modified with 0.4 and 0.8 wt.% of GSH to produce small-diameter blood vessels, as the material was found to: (i) have antioxidant properties, (ii) support VSMC and ASC viability and growth and (iii) provide an environment suitable for the initiation of cell differentiation.
The biographical notes of the two municipal physicians of Schweinfurt, Leonhard Bausch (1574 to 1636) and Johann Laurentius Bausch (1605-1665) and another three physicians (Johann Michael Fehr, Georg Balthasar Wohlfarth and Georg Balthasar Metzger) who founded the Academia Naturae Curiosorum together with the younger Bausch in 1652, show that this founding was initiated by a surprisingly homogenous group, sharing the same social, educational and professional background as well as ancestral and acquired experiences. They all had been influenced by the immigration fate of their families, the rapid rise to the politically or academically educated elite in the imperial city of Schweinfurt, worn out by war and plagues. They all had studied at universities in protestant territories of the Holy Roman Empire, finishing with an educational journey (peregrinatio academica), usually to Italy. Experience of the flourishing university life beyond the frontiers of the Holy Roman Empire laid waste by the "Teutsche Krieg", the great variety of academies in Italy, the narrowness of contemporary medicine and the inability of the individual to explore the immense variety of nature: all this leads to the founding of the Academia Naturae Curiosorum and it is the point of reference of the founding documents of 1651/1652, which were first printed in 1662 (Salve Academicum). What is innovative about this is not the establishment of an academy but the desired aim and the way of achieving this. The tenor of these documents--to medically explore the variety of the divine "res naturals" in a cooperative and regulated way for the benefit of medicine and mankind and to publish the results in monographes (utilitas by curiositas)--was condensed by the later Leopoldina to the still used motto "to explore nature for the benefit of mankind". Due to Breslau's municipal physician Philipp Jacob Sachs von Lewenhaimb (1627 - 1672) the publishing activities of the academy came into being. But before the death of BAUSCH only three titles could be published ad normam et formam Academiae Naturae Curiosorum in the context of the work programme: Sachs' Ampelographia (1661), Gammarologia (1665) and Bausch's Haematite et Aetite (1665). The way to international exchange, essentially created by SACHS, led to a new definition of academic tasks by critically reflecting other models (London, Paris, and Florence). Out of this reform process emerged the new Leges with 21 paragraphs (published in 1671). The new concept focussed on the issue of the journal exclusively for medicine and natural science as well as the striving for imperial recognition and privileges. The first volume of the Ephemerides could be presented in 1670: Miscellanea curiosa medico-physica Academiae Naturae Curiosorum sive Ephemeridum medico-physicarum Germanicarum curiosarum annus primus. The new journal, which is still published today under the title Nova Acta Leopoldina, represented the way to a successful future without completely abandoning the original concept of monographes. The imperial privileges (confirmation as imperial academy, confirmation of Leges, privilege to ban reprints) could be achieved in 1677. The privilege of Emperor Leopold I. of 7 August 1687 finally brought the academy, 35 years after it was founded, a coat of arms and imperial title--Sacri Romani Imperii Academia Caesareo-Leopoldina Naturae Curiosorum. President and Director Ephemeridum and their successors were raised to imperial personal physicians and nobility, combined with the title and rights of palatinate court ("Hofpfalzgrafen"), which also included the right to award doctorates.
Glyoxal-linked 2'-deoxyuridine 5'-O-mono- and triphosphates were synthesized through a CuAAC click reaction of 4-azidophenylglyoxal or a Sonogashira reaction of 4-bromophenylglyoxal with 5-ethynyl-dUMP or -dUTP. The triphosphates were used as substrates for enzymatic synthesis of modified DNA probes with KOD XL DNA polymerase. The glyoxal-linked nucleotides reacted with arginine-containing peptides to form stable imizadolone-linked conjugates. This reactive glyoxal modification in DNA was used for efficient bioconjugations and crosslinking with Arg-containing peptides or proteins (e. g., histones) and was found to be more reactive than previously reported 1,3-diketone-linked DNA probes.