Methyl β-lactoside [methyl β-D-galactopyranosyl-(1→4)-β-D-glucopyranoside] monohydrate: a solvomorphism study

Methyl β-lactoside [methyl β-D-galactopyranosyl-(1→4)-β-D-glucopyranoside] monohydrate, C13H24O11·H2O, (I), was obtained via spontaneous transformation of methyl β-lactoside methanol solvate, (II), during air-drying. Cremer–Pople puckering parameters indicate that the β-D-Galp (β-D-galactopyranosyl) and β-D-Glcp (β-D-glucopyranosyl) rings in (I) adopt slightly distorted 4 C 1 chair conformations, with the former distorted towards a boat form (B C1,C4) and the latter towards a twist-boat form (O5 S C2). Puckering parameters for (I) and (II) indicate that the conformation of the βGalp ring is slightly more affected than the βGlcp ring by the solvomorphism. Conformations of the terminal O-glycosidic linkages in (I) and (II) are virtually identical, whereas those of the internal O-glycosidic linkage show torsion-angle changes of 6° in both C—O bonds. The exocyclic hydroxymethyl group in the βGalp residue adopts a gt conformation (C4′ anti to O6′) in both (I) and (II), whereas that in the βGlcp residue adopts a gg (gauche–gauche) conformation (H5 anti to O6) in (II) and a gt (gauche–trans) conformation (C4 anti to O6) in (I). The latter conformational change is critical to the solvomorphism in that it allows water to participate in three hydrogen bonds in (I) as opposed to only two hydrogen bonds in (II), potentially producing a more energetically stable structure for (I) than for (II). Visual inspection of the crystalline lattice of (II) reveals channels in which methanol solvent resides and through which solvent might exchange during solvomorphism. These channels are less apparent in the crystalline lattice of (I).

Organoid and Primary Epithelial Cultures of Human Prostate Show the Key Role of the Epithelial-to-Mesenchymal Transition in Generation of Tissue-Specific Stromal Cells

The prostate gland (PG) is a small organ in the male reproductive system that is currently the focus of biomedical research due to its leading position in morbidity and mortality from the tissue-specific prostate cancer (PC). The PG epithelium, which undergoes a cancerous transformation, is formed and functions under the control of androgens. At the beginning of the disease, epithelial cells produce an androgen receptor (AR) and are sensitive to androgen-deprivation therapy. However, such therapy inevitably leads to the transition of the disease to the castration-resistant prostate cancer (CRPC), which manifests itself in metastasis and rapid mortality. In CRPC, the cells of the prostate epithelium change their phenotype, that may be associated with AR mutation and loss the sensitivity to specific therapy. The mechanism of PG phenotypic transformation may be hidden in the interaction and formation of the stromal and epithelial cells, which are evident during the establishment of the primary cultures. The aim of this study was to investigate the generation of human PG stromal cells in primary stromal and organoid cultures. We found that, in contrast to the rapid appearance and formation of a homogeneous population of mesenchymal cells in primary stromal cultures of most tissues, human PG cell cultures are formed initially from epithelial cells. They appear in the second week of cultivation and produce cytokeratins (CKs). A homogeneous population of mesenchymal cells producing vimentin is formed only at the end of the fourth week of cultivation. It is accompanied by the disappearance of epithelial cells. At the same time, some epithelial cells simultaneously produce CKs and vimentin. In PG organoid cultures, there is often a concomitant growth of epithelial, but not mesenchymal, cells on culture plastic. During the cultivation of epithelial cells arising from the organoid cultures, they, like the cells of the primary epithelium, exhibit the ability to spontaneous transformation into mesenchymal cells and simultaneously produce CKs and vimentin. Our data suggest that in primary and organoid PG cultures, stromal cells can be formed from epithelium due to the epithelial-to-mesenchymal transition (EMT). The tendency of PG epithelium toward spontaneous EMT may contribute to the mechanism of high sensitivity of prostate tissue to malignant transformation and metastasis. Understanding this mechanism may contribute to the development of effective antitumor therapy of prostate cancer.

Optical power limiter in the femtosecond filamentation regime

We present the use of a power limiting apparatus to evaluate ultrafast optical nonlinearities of transparent liquids (water and ethanol) in the femtosecond filamentation regime. The setup has been previously employed for the same purpose, however, in a longer pulsewidth (> 20 ps) regime, which leads to an ambiguous evaluation of the critical power for self-focusing. The uncertainty originates from the existence of a threshold power for optical breakdown well below the critical power for self-focusing within this timeframe. Contrarily, using the proposed apparatus in the femtosecond regime, we observe for the first time a unique optical response, which features the underlying physics of laser filamentation. Importantly, we demonstrate a dependence of the optical transmission of the power limiter on its geometrical, imaging characteristics and the conditions under which a distinct demarcation for the critical power for self-focusing can be determined. The result is supported by numerical simulations, which indicate that the features of the observed power-dependent optical response of the power limiting setup are physically related to the spontaneous transformation of the laser pulses into nonlinear conical waves.

Alterations of epigenetic regulators and P53 mutations in murine mesenchymal stem cell cultures: A possible mechanism of spontaneous transformation

BACKGROUND: Recent studies demonstrated the involvement of mesenchymal stem/stromal cells (MSCs) in carcinogenesis, but the molecular mechanism behind this transformation is still obscured. OBJECTIVE: To screen both the expression levels of polycomb and trithorax epigenetic regulators and TrP53 mutations in early and late MSC culture passages in an attempt to decipher the mechanism of spontaneous transformation. METHODS: The study was conducted on early and late passages of MSC culture model from C57BL/6J mice. The expression profile of 84 epigenetic regulators was examined using RT2 profiler PCR array. TrP53 mutations in the DNA binding domain was screened. Codons, amino acids positions and the corresponding human variants were detected in P53 sequences. RESULTS: Sixty-two epigenetic regulators were dysregulated. Abnormalities were detected starting the third passage. Nine regulators were dysregulated in all passages. (C>G) substitution P53 mutation was detected in passage 3 resulting in Ser152Arg substitution. Passages 6, 9, 12 and the last passage showed T>C substitution resulting in Cys235Arg substitution. The last passage had T deletion and A insertion resulting in frame shift mutations changing the p.Phe286Ser and p.Asn103Lys respectively. CONCLUSION: In vitro expanded MSCs undergo transformation through alteration of epigenetic regulators which results in genomic instability and frequent P53 mutations.

Interfacial Compatibility on the Crystal Transformation of Isotactic Poly (1-Butene)/Herb Residue Composite

Isotactic poly (1-butene) (iPB) has excellent properties which are recognized as a green and energy saving product. However, the most stable and valuable crystal form I had a spontaneous transformation that took as long as seven days to complete. As a special solid waste, the herb residue (HR) is rich in cellulose which has great potential to accelerate the crystal transformation of the iPB. However, the polarity of HR results in the interface compatibility with non-polar iPB. In this study, the HR was modified by silane coupling agent (KH570) to obtain KHR and the iPB/HR composite was prepared. The FTIR spectrum was indicated that the organic functional groups of KH570 successfully graft onto the surface of HR and the water contact angle test was indicated that the hydrophilicity of the KHR was greatly decreased. The complete crystal transformation time is 7 days for iPB, 6 days for iPB+5% HR but only 3 days for iPB+5% KHR. The addition of the HR and KHR improve the thermal stability of the composite and this beneficial effect is more obvious for KHR. After annealing for 5 days, the physical properties value include tensile strength, flexural strength, and HDT of iPB+5% HR reach that of pure iPB after annealing for 7 days, but only 3 days for iPB+5% KHR. The TG analysis and SEM photographs give clear evidence that the beneficial effect of KH570 modified HR on improving the interface compatibility with iPB.

Transformed Canine and Murine Mesenchymal Stem Cells as a Model for Sarcoma with Complex Genomics

Sarcomas are rare mesenchymal tumors with a broad histological spectrum, but they can be divided into two groups based on molecular pathology: sarcomas with simple or complex genomics. Tumors with complex genomics can have aneuploidy and copy number gains and losses, which hampers the detection of early, initiating events in tumorigenesis. Often, no benign precursors are known, which is why good models are essential. The mesenchymal stem cell (MSC) is the presumed cell of origin of sarcoma. In this study, MSCs of murine and canine origin are used as a model to identify driver events for sarcomas with complex genomic alterations as they transform spontaneously after long-term culture. All transformed murine but not canine MSCs formed sarcomas after subcutaneous injection in mice. Using whole genome sequencing, spontaneously transformed murine and canine MSCs displayed a complex karyotype with aneuploidy, point mutations, structural variants, inter-chromosomal translocations, and copy number gains and losses. Cross-species analysis revealed that point mutations in Tp53/Trp53 are common in transformed murine and canine MSCs. Murine MSCs with a cre-recombinase induced deletion of exon 2-10 of Trp53 transformed earlier compared to wild-type murine MSCs, confirming the contribution of loss of p53 to spontaneous transformation. Our comparative approach using transformed murine and canine MSCs points to a crucial role for p53 loss in the formation of sarcomas with complex genomics.