Analysis of The Town Officer (1791-1815): The earliest American treatise on municipal accounting?

Recent research has produced the earliest known treatise on Accounting written by an American. Samuel Freeman\u27s The Town Officer [1791] is significant in that it recommended double-entry fund accounting for municipalities. The paper analyzes and compares Freeman\u27s objectives of a plain and regular Method to modem municipal accounting concepts as articulated by the GASB. Additionally, the entries and the accounts recommended by Freeman are analyzed and compared to modern municipal accounting evidenced in current textbook material. These analyses show The Town Officer to be a significant contribution to accounting literature not only for its 1791 publication date, but also for the similarity of its content to present day municipal accounting objectives and requirements

Small RNA changes en route to distinct cellular states of induced pluripotency

MicroRNAs (miRNAs) are critical to somatic cell reprogramming into induced pluripotent stem cells (iPSCs), however, exactly how miRNA expression changes support the transition to pluripotency requires further investigation. Here we use a murine secondary reprogramming system to sample cellular trajectories towards iPSCs or a novel pluripotent ‘F-class’ state and perform small RNA sequencing. We detect sweeping changes in an early and a late wave, revealing that distinct miRNA milieus characterize alternate states of pluripotency. miRNA isoform expression is common but surprisingly varies little between cell states. Referencing other omic data sets generated in parallel, we find that miRNA expression is changed through transcriptional and post-transcriptional mechanisms. miRNA transcription is commonly regulated by dynamic histone modification, while DNA methylation/demethylation consolidates these changes at multiple loci. Importantly, our results suggest that a novel subset of distinctly expressed miRNAs supports pluripotency in the F-class state, substituting for miRNAs that serve such roles in iPSCs

Excited State Vibrations of Isotopically Labeled FMN Free and Bound to a Light–Oxygen–Voltage (LOV) Protein

Flavoproteins are important blue light sensors in photobiology and play a key role in optogenetics. The characterization of their excited state structure and dynamics is thus an important objective. Here, we present a detailed study of excited state vibrational spectra of flavin mononucleotide (FMN), in solution and bound to the LOV-2 (Light-Oxygen-Voltage) domain of Avena sativa phototropin. Vibrational frequencies are determined for the optically excited singlet state and the reactive triplet state, through resonant ultrafast femtosecond stimulated Raman spectroscopy (FSRS). To assign the observed spectra, vibrational frequencies of the excited states are calculated using density functional theory, and both measurement and theory are applied to four different isotopologues of FMN. Excited state mode assignments are refined in both states, and their sensitivity to deuteration and protein environment are investigated. We show that resonant FSRS provides a useful tool for characterizing photoactive flavoproteins and is able to highlight chromophore localized modes and to record hydrogen/deuterium exchange

Prepatterning in the Stem Cell Compartment

The mechanism by which an apparently uniform population of cells can generate a heterogeneous population of differentiated derivatives is a fundamental aspect of pluripotent and multipotent stem cell behaviour. One possibility is that the environment and the differentiation cues to which the cells are exposed are not uniform. An alternative, but not mutually exclusive possibility is that the observed heterogeneity arises from the stem cells themselves through the existence of different interconvertible substates that pre-exist before the cells commit to differentiate. We have tested this hypothesis in the case of apparently homogeneous pluripotent human embryonal carcinoma (EC) stem cells, which do not follow a uniform pattern of differentiation when exposed to retinoic acid. Instead, they produce differentiated progeny that include both neuronal and non-neural phenotypes. Our results suggest that pluripotent NTERA2 stem cells oscillate between functionally distinct substates that are primed to select distinct lineages when differentiation is induced

Monitoring neuronal differentiation in the embryonal carcinoma cell line NTERA2

NTERA2 embryonal carcinoma cells are pluripotent cells that originated from a metastasis of a testicular cancer. Previous research has demonstrated the ability of NTERA2 cells to reliably differentiate into a neuronal cell fate, upon exposure to retinoic acid. Although this provides a useful tool for the study of neuronal differentiation, until now a thorough investigation of basic in vitro conditions was absent. This study has systematically analysed NTERA2 differentiation as a population and at the single cell level. Prolonged RA exposure and high cell density has been shown to be required for the successful production of neurons, demonstrating that NTERA2 cells follow a nonautonomous path of differentiation towards a neuronal phenotype. Gap junction communication is required for NTERA2 neuronal differentiation and is thought to contribute to the density dependence of neuronal differentiation. The importance of Wnt signalling has also been examined and it has been found that elevated Wnt signalling drives RA mediated cell differentiation to a non-neuronal fate. Single cell analysis has revealed that functional heterogeneity resides within the undifferentiated stem cell population. SSEA3 expression was successfully used to enrich for functional stem cells however examination of SSEA3 expression does not enable the prediction of single cell behaviour. Diversity and instability of chromosomal karyotype in the NTERA2 cell line suggests that single cell heterogeneity is partially derived from karyotypic instability.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Monitoring neuronal differentiation in the embryonal carcinoma cell line NTERA2

NTERA2 embryonal carcinoma cells are pluripotent cells that originated from a metastasis of a testicular cancer. Previous research has demonstrated the ability of NTERA2 cells to reliably differentiate into a neuronal cell fate, upon exposure to retinoic acid. Although this provides a useful tool for the study of neuronal differentiation, until now a thorough investigation of basic in vitro conditions was absent. This study has systematically analysed NTERA2 differentiation as a population and at the single cell level. Prolonged RA exposure and high cell density has been shown to be required for the successful production of neurons, demonstrating that NTERA2 cells follow a nonautonomous path of differentiation towards a neuronal phenotype. Gap junction communication is required for NTERA2 neuronal differentiation and is thought to contribute to the density dependence of neuronal differentiation. The importance of Wnt signalling has also been examined and it has been found that elevated Wnt signalling drives RA mediated cell differentiation to a non-neuronal fate. Single cell analysis has revealed that functional heterogeneity resides within the undifferentiated stem cell population. SSEA3 expression was successfully used to enrich for functional stem cells however examination of SSEA3 expression does not enable the prediction of single cell behaviour. Diversity and instability of chromosomal karyotype in the NTERA2 cell line suggests that single cell heterogeneity is partially derived from karyotypic instability.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Local BMP-SMAD1 Signaling Increases LIF Receptor-Dependent STAT3 Responsiveness and Primed-to-Naive Mouse Pluripotent Stem Cell Conversion Frequency

Conversion of EpiSCs to naive ESCs is a rare event that is driven by the reestablishment of the naive transcription factor network. In mice, STAT3 activation is sufficient to drive conversion of EpiSCs to the naive pluripotent stem cell (PSC) state. However, the lack of responsiveness of EpiSCs to LIF presents a bottleneck in this conversion process. Here, we demonstrate that local accumulation of BMP-SMAD1 signaling, in cooperation with GP130 ligands, enhances the recovery of LIF responsiveness by directly controlling transcription of the LIF receptor (Lif-r). Addition of BMP and LIF to EpiSCs increases both LIF responsiveness and conversion frequencies to naive PSCs. Mechanistically, we show that the transcriptional cofactor P300 plays a critical role by mediating complex formation between STAT3 and SMAD1. This demonstration of how the local microenvironment or stem cell niche reactivates dormant signaling responsiveness and developmental potential may be applicable to other stem cell niche-containing systems

An analysis of The Town Officer (1791-1815): The earliest American treatise on municipal accounting?

Recent research has produced the earliest known treatise on Accounting written by an American. Samuel Freeman’s The Town Officer [1791] is significant in that it recommended double-entry fund accounting for municipalities. The paper analyzes and compares Freeman’s objectives of “a plain and regular Method” to modern municipal accounting concepts as articulated by the GASB. Additionally, the entries and the accounts recommended by Freeman are analyzed and compared to modern municipal accounting evidenced in current textbook material. These analyses show The Town Officer to be a significant contribution to accounting literature not only for its 1791 publication date, but also for the similarity of its content to present day municipal accounting objectives and requirements