The Differentiation and Stress Response Factor XBP-1 Drives Multiple Myeloma Pathogenesis

Multiple myeloma (MM) evolves from a highly prevalent premalignant condition termed MGUS. The factors underlying the malignant transformation of MGUS are unknown. We report a MGUS/MM phenotype in transgenic mice with Eμ-directed expression of the XBP-1 spliced isoform (XBP-1s), a factor governing unfolded protein/ER stress response and plasma-cell development. Eμ-XBP-1s elicited elevated serum Ig and skin alterations. With age, Eμ-xbp-1s transgenics develop features diagnostic of human MM, including bone lytic lesions and subendothelial Ig deposition. Furthermore, transcriptional profiles of Eμ-xbp-1s lymphoid and MM cells show aberrant expression of known human MM dysregulated genes. The similarities of this model with the human disease, coupled with documented frequent XBP-1s overexpression in human MM, serve to implicate XBP-1s dysregulation in MM pathogenesis

Simplified Method for <i>Agrobacterium</i>-Mediated Genetic Transformation of <i>Populus</i> x <i>berolinensis</i> K. Koch

The rapid advancement of genetic technologies has made it possible to modify various plants through both genetic transformation and gene editing techniques. Poplar, with its rapid in vitro growth and regeneration enabling high rates of micropropagation, has emerged as a model system for the genetic transformation of woody plants. In this study, Populus × berolinensis K. Koch. (Berlin poplar) was chosen as the model organism due to its narrow leaves and spindle-shaped crown, which make it highly suitable for in vitro manipulations. Various protocols for the Agrobacterium-mediated transformation of poplar species have been developed to date. However, the genetic transformation procedures are often constrained by the complexity of the nutrient media used for plant regeneration and growth, which could potentially be simplified. Our study presents a cheaper, simplified, and relatively fast protocol for the Agrobacterium-mediated transformation of Berlin poplar. The protocol involved using internode sections without axillary buds as explants, which were co-cultivated in 10 µL droplets of bacterial suspension directly on the surface of a solid agar-based medium without rinsing and sterile paper drying after inoculation. We used only one regeneration Murashige and Skoogbased medium supplemented with BA (0.2 mg·L−1), TDZ (0.02 mg·L−1), and NAA (0.01 mg·L−1). Acetosyringone was not used as an induction agent for vir genes during the genetic transformation. Applying our protocol and using the binary plasmid pBI121 carrying the nptII selective and uidA reporter genes, we obtained the six transgenic lines of poplar. Transgenesis was confirmed through a PCR-based screening of kanamycin-selected regenerants for the presence of both mentioned genes, Sanger sequencing, and tests for detecting the maintained activity of both genes. The transformation efficiency, considering the 100 explants taken originally, was 6%

Eranthis Salisb. (Ranunculaceae) in South Siberia: Insights into Phylogeography and Taxonomy

Eranthis Salisb. (Ranunculaceae) is a herbaceous plant genus, including few species disjunctively distributed throughout the temperate zone from Southeastern Europe to Eastern Asia. Until recently, only Eranthis sibirica DC. was known in South Siberia, being considered endemic and tertiary relict. Not long ago, Eranthis tanhoensis Erst was also described in Siberia. We report here a reconstruction of the phylogenetic relationships between the Siberian Eranthis species based on nuclear (ITS) and plastid (trnL + trnL-trnF + trnH-psbA) DNA. The phylogeographic structure of Siberian Eranthis is distinguished by the presence of the two &ldquo;eastern&rdquo; and &ldquo;western&rdquo; supergroups, which most likely formed as a result of disjunction caused by active mountain uplifts during the late Neogene&ndash;early Quaternary and subsequent progressive Pleistocene cooling. The eastern supergroup combines lineage I, containing populations from the eastern Khamar-Daban Ridge, the Eastern Sayan Mountains, and the Tannu-Ola Ridge, and lineage II containing western Khamar-Daban populations. The western supergroup includes only lineage III, containing Western Sayan populations. Our data clearly show that E. tanhoensis is nested in the E. sibirica clade, thereby indicating that its description as a separate species is unjustified, as it compromises the monophyletic status of E. sibirica. Therefore, we suggest here to consider E. tanhoensis as a synonym of E. sibirica

Activity of SQ641, a Capuramycin Analog, in a Murine Model of Tuberculosis ▿

New delivery vehicles and routes of delivery were developed for the capuramycin analogue SQ641. While this compound has remarkable in vitro potency against Mycobacterium tuberculosis, it has low solubility in water and poor intracellular activity. We demonstrate here that SQ641 dissolved in the water-soluble vitamin E analogue α-tocopheryl polyethylene glycol 1000 succinate (TPGS) or incorporated into TPGS-micelles has significant activity in a mouse model of tuberculosis

Lake Baikal's amphipod fauna threatened by climate change, pollutants and invaders?

Lake Baikal is a unique ecosystem being the oldest and deepest freshwater lake on earth. Due to stable conditions over millions of years it is suggested that Baikal endemic amphipods are vulnerable to climate change, pollutants and invading species. In this study we investigated the effects of elevated temperature and cadmium levels on the physiological performances of the Baikal endemic amphipods Eulimnogammarus verrucosus and Eulimnogammarus cyaneus and the ubiquitous Palearctic amphipod Gammarus lacustris. This amphipod is regularly introduced into Lake Baikal and a potential invader. We focused on ion and acid/base regulation, oxygen consumption and ventilatory rates as performance parameters. First results showed that magnesium levels in hemolymph decreased during temperature increase (6-30°C, 1°C h-1) in all species investigated while cadmium did not have any effect. Furthermore, Baikal amphipods are not particularly sensitive to cadmium compared to other amphipod species as demonstrated by mortality experiments. The study revealed that E. verrucosus is living under stress conditions when temperatures exceeded 12-14°C while E. cyaneus is able to compensate for the increased oxygen demand up to 27°C (6-30°C, 0.8°C d-1). Given that E. cyaneus and G. lacustris showed similar resting metabolic rates this cannot explain why G. lacustris is not able to establish in Lake Baikal. Differences in the physiological performance under stress conditions between the two studied Baikal species are large. Hence it is supposed to be species-specific to what extent global change will affect Baikal endemics

Table S6 from Development of a Novel DNA Mono-alkylator Platform for Antibody–Drug Conjugates

Table shows Cytotoxicity comparisons between Biaryl PBD payloads 4 and 20 vs IGN 2</p

Figure S6 from Development of a Novel DNA Mono-alkylator Platform for Antibody–Drug Conjugates

Figure shows comet assay results</p

Table S5 from Development of a Novel DNA Mono-alkylator Platform for Antibody–Drug Conjugates

Table shows TROP2 receptor quantification on DLD1 and HT29 cells</p