Individuals generally form their unique memories from shared experiences, yet the neural representational mechanisms underlying this subjectiveness of memory are poorly understood. The current study addressed this important question from the cross-subject neural representational perspective, leveraging a large functional magnetic resonance imaging dataset (n = 415) of a face-name associative memory task. We found that individuals memory abilities were predicted by their synchronization to the group-averaged, canonical trial-by-trial activation level and, to a lesser degree, by their similarity to the group-averaged representational patterns during encoding. More importantly, the memory content shared between pairs of participants could be predicted by their shared local neural activation pattern, particularly in the angular gyrus and ventromedial prefrontal cortex, even after controlling for differences in memory abilities. These results uncover neural representational mechanisms for individualized memory and underscore the constructive nature of episodic memory.

Gemcitabine metabolites cause the termination of DNA replication and induction of apoptosis. We determined whether subtherapeutic "microdoses" of gemcitabine are incorporated into DNA at levels that correlate to drug cytotoxicity. A pair of nearly isogenic bladder cancer cell lines differing in resistance to several chemotherapy drugs were treated with various concentrations of ¹⁴C-labeled gemcitabine for 4-24 h. Drug incorporation into DNA was determined by accelerator mass spectrometry. A mechanistic analysis determined that RRM2, a DNA synthesis protein and a known resistance factor, substantially mediated gemcitabine toxicity. These results support gemcitabine levels in DNA as a potential biomarker of drug cytotoxicity.

Abstract Objective To determine if a human bladder cancer-specific peptide named PLZ4 can target canine bladder cancer cells. Experimental Design The binding of PLZ4 to five established canine invasive transitional cell carcinoma (TCC) cell lines and to normal canine bladder urothelial cells was determined using the whole cell binding assay and an affinitofluorescence assay. The WST-8 assay was performed to determine whether PLZ4 affected cell viability. In vivo tumor-specific homing/targeting property and biodistribution of PLZ4 was performed in a mouse xenograft model via tail vein injection and was confirmed with ex vivo imaging. Results PLZ4 exhibited high affinity and specific dose-dependent binding to canine bladder TCC cell lines, but not to normal canine urothelial cells. No significant changes in cell viability or proliferation were observed upon incubation with PLZ4. The in vivo and ex vivo optical imaging study showed that, when linked with the near-infrared fluorescent dye Cy5.5, PLZ4 substantially accumulated at the canine bladder cancer foci in the mouse xenograft model as compared to the control. Conclusions and Clinical Relevance PLZ4 can specifically bind to canine bladder cancer cells. This suggests that the preclinical studies of PLZ4 as a potential diagnostic and therapeutic agent can be performed in dogs with naturally occurring bladder cancer, and that PLZ4 can possibly be developed in the management of canine bladder cancer.

Perovskite photovoltaics, typically based on a solution-processed perovskite layer with a film thickness of a few hundred nanometres, have emerged as a leading thin-film photovoltaic technology. Nevertheless, many critical issues pose challenges to its commercialization progress, including industrial compatibility, stability, scalability and reliability. A thicker perovskite film on a scale of micrometres could mitigate these issues. However, the efficiencies of thick-film perovskite cells lag behind those with nanometre film thickness. With the mechanism remaining elusive, the community has long been under the impression that the limiting factor lies in the short carrier lifetime as a result of defects. Here, by constructing a perovskite system with extraordinarily long carrier lifetime, we rule out the restrictions of carrier lifetime on the device performance. Through this, we unveil the critical role of the ignored lattice strain in thick films. Our results provide insights into the factors limiting the performance of thick-film perovskite devices.

We report herein the development, functional and molecular characterization of an isogenic, paired bladder cancer cell culture model system for studying platinum drug resistance. The 5637 human bladder cancer cell line was cultured over ten months with stepwise increases in oxaliplatin concentration to generate a drug resistant 5637R sub cell line. The MTT assay was used to measure the cytotoxicity of several bladder cancer drugs. Liquid scintillation counting allowed quantification of cellular drug uptake and efflux of radiolabeled oxaliplatin and carboplatin. The impact of intracellular drug inactivation was assessed by chemical modulation of glutathione levels. Oxaliplatin- and carboplatin-DNA adduct formation and repair was measured using accelerator mass spectrometry. Resistance factors including apoptosis, growth factor signaling and others were assessed with RNAseq of both cell lines and included confirmation of selected transcripts by RT-PCR. Oxaliplatin, carboplatin, cisplatin and gemcitabine were significantly less cytotoxic to 5637R cells compared to the 5637 cells. In contrast, doxorubicin, methotrexate and vinblastine had no cell line dependent difference in cytotoxicity. Upon exposure to therapeutically relevant doses of oxaliplatin, 5637R cells had lower drug-DNA adduct levels than 5637 cells. This difference was partially accounted for by pre-DNA damage mechanisms such as drug uptake and intracellular inactivation by glutathione, as well as faster oxaliplatin-DNA adduct repair. In contrast, both cell lines had no significant differences in carboplatin cell uptake, efflux and drug-DNA adduct formation and repair, suggesting distinct resistance mechanisms for these two closely related drugs. The functional studies were augmented by RNAseq analysis, which demonstrated a significant change in expression of 83 transcripts, including 50 known genes and 22 novel transcripts. Most of the transcripts were not previously associated with bladder cancer chemoresistance. This model system and the associated phenotypic and genotypic data has the potential to identify some novel details of resistance mechanisms of clinical importance to bladder cancer.