Genetic dissection of the glutamatergic neuron system in cerebral cortex.

Diverse types of glutamatergic pyramidal neurons mediate the myriad processing streams and output channels of the cerebral cortex1,2, yet all derive from neural progenitors of the embryonic dorsal telencephalon3,4. Here we establish genetic strategies and tools for dissecting and fate-mapping subpopulations of pyramidal neurons on the basis of their developmental and molecular programs. We leverage key transcription factors and effector genes to systematically target temporal patterning programs in progenitors and differentiation programs in postmitotic neurons. We generated over a dozen temporally inducible mouse Cre and Flp knock-in driver lines to enable the combinatorial targeting of major progenitor types and projection classes. Combinatorial strategies confer viral access to subsets of pyramidal neurons defined by developmental origin, marker expression, anatomical location and projection targets. These strategies establish an experimental framework for understanding the hierarchical organization and developmental trajectory of subpopulations of pyramidal neurons that assemble cortical processing networks and output channels

Cellular anatomy of the mouse primary motor cortex.

An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated and interpreted1. Here, as part of the collaborative Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based anatomical description of one exemplar brain structure, the mouse primary motor cortex, upper limb area (MOp-ul). Using genetic and viral labelling, barcoded anatomy resolved by sequencing, single-neuron reconstruction, whole-brain imaging and cloud-based neuroinformatics tools, we delineated the MOp-ul in 3D and refined its sublaminar organization. We defined around two dozen projection neuron types in the MOp-ul and derived an input-output wiring diagram, which will facilitate future analyses of motor control circuitry across molecular, cellular and system levels. This work provides a roadmap towards a comprehensive cellular-resolution description of mammalian brain architecture

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

Auditor Concentration of Listed Public Companies on International Stock Exchanges

This paper explores the concentration of audit services provided to listed public companies on the Stock Exchanges of Canada, Hong Kong, London, and Singapore. The Canadian and London stock exchanges are chosen as representatives of the North American and European markets, while the Hong Kong and Singapore exchanges represent the newly developed Asia Pacific markets. Public accounting firms have benefited from the globalisation trends by expanding their own markets. The reason frequently mentioned for the mergers of the Big 8 accounting firms to form the Big 6 is that they want to increase their international presence and be in a better position to service multinationals in different markets. However, previous studies of concentration of firms in providing auditing services have all been restricted to the USA or individual countries. This study uses both concentration ratios and Herfindahl indices to examine concentration of audit firms in the international stock exchanges. The results indicate a disparate competition amongst the larger firms in each of the Canadian, Hong Kong, London, and Singapore markets. In all of the four markets, the concentration ratios and Herfindahl indices calculated indicate a lack of competition even at the four firm level. This imbalance was very pronounced when the size of the companies audited is considered using their reported total assets. We also present the market shares of the leading six firms in each exchange and discuss some implications of this disparate competition

Perceived Value of Mandatory Audits of Small Companies

As a territory of the UK (until 1 July 1997), Hong Kong followed the UK accounting and auditing standards quite closely, in most cases mirroring the requirements. However, there was a departure regarding the elimination of the statutory audit of small private companies in the UK in 1994, but this was not followed in Hong Kong. An audit is not required for small private companies in the USA either. This study evaluates the perceived value of the small companies’ audit in the opinion of two interest groups that are most affected by this requirement: small private limited companies and small audit firms. Results indicate that both groups of respondents consider the audit to be a valuable experience. While this result is not unexpected from the partners/proprietors of small audit firms, who benefit most from the mandatory audit requirement, it is a surprise from the small companies’ perspective

An International Study of Cross-sectional Variations in Audit Fees

Most previous studies in the market for auditing services and modeling of audit fees have been limited to either a single country (e.g., Johnson et al. 1995) or a single region (e.g., Simon et al. 1992) or a collection across regions (Haskin & Williams 1988). The main studies to examine cross‐country audit fee models are Taylor and Simon (1999) and Wingate (1994). This study extends their previous work by building an audit fees model for 12 countries in Europe, Africa, and Asia. A more comprehensive model is tested which includes the developing stage of the country, (a variable not yet tested) and industry classifications (a variable not tested by most previous studies). Data were compiled from the annual reports published in the International Accounting and Auditing Trends, Fourth Edition (1995) over 1989–1993 by Center for International Financial Analysis and Research (CIFAR). Our results show that, on average, companies in developed countries pay higher audit fees than companies in developing countries. Companies in manufacturing industries for most of the countries studied have the lowest fees charged to them, as compared to the other four industries, presumably because auditors get more training in auditing manufacturing companies than other companies. As in previous studies, our results show that the Big 6 audit firms charge higher fees than non‐Big 6 auditors. The fee premium may be due to the need for quality‐differentiated audits in the emerging capital markets, or due to the brand name reputation enjoyed by the Big 6

An Experimental Study of Hong Kong and Chinese Auditors\u27 Perceptions of Auditor Independence

The objective of this study is to compare the perceptions of Chinese and Hong Kong auditors towards auditor independence. There is growing concern about auditors\u27 independence in the Peoples Republic of China (PRC) as a result of the rapidly changing business environment. These include the fast economic growth, changes in the accounting and auditing requirements including increases in demand for auditing services, competition and the status of accounting profession in the PRC. The purpose of this study is to investigate whether these changes affect the perceptions of auditor independence. The factors used in this study include the size of audit fee, provision of management advisory services, tenure of services provided and the relationship between the client and the auditor. The data were analyzed using analysis of variance (ANOVA). The overall hypothesis of a difference in the perceptions of Hong Kong and Chinese auditors was found to be significant. The results provide some indications of the stage of development of the accounting profession in China and the directions in harmonizing with international practices. Though there are some limitations of this study, it provides information for limited research in the accounting profession in China and highlights several areas for future study