Integration of a Phosphatase Cascade with the MAP Kinase Pathway provides for a Novel Signal Processing Function

We mathematically modeled the receptor-activated MAP kinase signaling by incorporating the regulation through cellular phosphatases. Activation induced the alignment of a phosphatase cascade in parallel with the MAP kinase pathway. A novel regulatory motif was thus generated, providing for the combinatorial control of each MAPK intermediate. This ensured a non-linear mode of signal transmission with the output being shaped by the balance between the strength of input signal, and the activity gradient along the phosphatase axis. Shifts in this balance yielded modulations in topology of the motif, thereby expanding the repertoire of output responses. Thus we identify an added dimension to signal processing, wherein the output response to an external stimulus is additionally filtered through indicators that define the phenotypic status of the cell.Comment: Whole Manuscript 33 pages inclduing Main text, 7 Figures and Supporting Informatio

Narrowing the communication gap in internationally distributed teams: the case of software-development teams in Sri Lanka and Japan

Communication between geographically separated subgroups in internationally distributed teams (IDTs) is quite challenging because their communication is relatively sparse and relies heavily on electronic media. In the current study, we employed a grounded theory approach and conducted an in-depth case study of two IDTs with subgroups in Sri Lanka and Japan to investigate why communication problems occur between the subgroups and how these can be solved. The findings indicated that although language fluency did not pose a serious threat, the teams encountered communication problems because they did not develop a well-shared team mental model (TMM). Our study further revealed that project process models (PPMs) play a key role in developing well-shared TMMs in IDTs, and the underlying process is facilitated by bridge individuals. Our findings extend the knowledge-sharing perspective of IDTs by focusing on the role of PPM, TMM, and bridge individuals in the communication process in IDTs

Addressing the Racial Wealth Divide Through Community-Led Social Change with Innovation Works

Within Baltimore, there has been a history of economic disparity, where communities including black, BIPOC, and women led small businesses are historically disenfranchised. Our community partner, Innovation Works, addresses this issue by providing tools and instruments that begin to challenge the systemic racial wealth divide in Baltimore, Maryland. We analyzed ways to enhance the experience for future participants of the Investor Showcase (an Innovation Works hosted event for social entrepreneurs to pitch their business in front of investors). Through surveys, in depth interviews, and a focus group, we assembled a multimethod primary data set. Our respondent pool was comprised of social entrepreneurs (small business leaders looking to solve community based issues), mentors, and investors within Innovation Works’ network. We used a multimethod approach to produce quantitative and qualitative analysis, in which our results indicate that Innovation Works provides necessary skills and resources for local organizations to grow their programs, benefiting marginalized groups. In addition to identifying successful program elements, we also analyzed strategies to improve future resource allocation, participant preparation for external funding, and growth in community networks. Our findings provide Innovation Works with a series of recommendations speaking to continuing current practices and strategies to enhance skill building, specifically developed to aid social entrepreneurs who lack opportunities to develop their business, therefore indirectly addressing the racial wealth gap

How Inpatriates Internalize Corporate Values at Headquarters: The Role of Developmental Job Assignments and Psychosocial Mentoring

Multinational companies (MNCs) often invite foreign subsidiary employees or inpatriates to their headquarters (HQ) to internalize the MNCs’ corporate values and transfer those values to their subsidiaries after repatriation. However, there is a lack of understanding about how and why inpatriates internalize these corporate values during their HQ experiences. By integrating the perspectives of international adjustment and organizational socialization with that of on-the-job learning, we develop a model wherein the job-related and psychosocial factors that inpatriates encounter at HQ promote their internalization of corporate values. Using a sample of 110 foreign subsidiary employee–supervisor dyads from the HQ of a Japanese MNC to which the employees were assigned as inpatriates, we found that developmental job assignments and psychosocial mentoring during inpatriation influenced the internalization of corporate values, which was partially and sequentially mediated by proactive socialization behavior and organizational identification. This study’s findings have significant implications for the theory and practice of inpatriation management, particularly with regard to how MNCs promote the internalization of corporate values among inpatriates

Optogenetic control of apical constriction induces synthetic morphogenesis in mammalian tissues

© The Author(s) 2022The emerging field of synthetic developmental biology proposes bottom-up approaches to examine the contribution of each cellular process to complex morphogenesis. However, the shortage of tools to manipulate three-dimensional (3D) shapes of mammalian tissues hinders the progress of the field. Here we report the development of OptoShroom3, an optogenetic tool that achieves fast spatiotemporal control of apical constriction in mammalian epithelia. Activation of OptoShroom3 through illumination in an epithelial Madin-Darby Canine Kidney (MDCK) cell sheet reduces the apical surface of the stimulated cells and causes displacements in the adjacent regions. Light-induced apical constriction provokes the folding of epithelial cell colonies on soft gels. Its application to murine and human neural organoids leads to thickening of neuroepithelia, apical lumen reduction in optic vesicles, and flattening in neuroectodermal tissues. These results show that spatiotemporal control of apical constriction can trigger several types of 3D deformation depending on the initial tissue context.his work was supported by internal grants from RIKEN and EMBL; Grant-in-Aid for Scientific research (KAKENHI) programs from Japanese Ministry of Education, Culture, Sports, Science, and Technology (MEXT) (16H06170 and 18H04769 to M.E.); Research foundation for OptoScience and Technology (to M.E.). X.T. is funded by European Research Council (Adv-883739) and La Caixa Foundation (LCF/PR/HR20/52400004). IBEC is a recipient of a Severo Ochoa Award of Excellence from the MINECO. M.B.-P. is funded by MICINN (FPI grant, PRE2019-088998)Peer ReviewedArticle signat per 10 autors/es: Guillermo Martínez-Ara, Núria Taberner, Mami Takayama, Elissavet Sandaltzopoulou, Casandra E. Villava, Miquel Bosch-Padrós, Nozomu Takata, Xavier Trepat, Mototsugu Eiraku and Miki Ebisuya.Postprint (published version

lincRNAs act in the circuitry controlling pluripotency and differentiation

Although thousands of large intergenic non-coding RNAs (lincRNAs) have been identified in mammals, few have been functionally characterized, leading to debate about their biological role. To address this, we performed loss-of-function studies on most lincRNAs expressed in mouse embryonic stem (ES) cells and characterized the effects on gene expression. Here we show that knockdown of lincRNAs has major consequences on gene expression patterns, comparable to knockdown of well-known ES cell regulators. Notably, lincRNAs primarily affect gene expression in trans. Knockdown of dozens of lincRNAs causes either exit from the pluripotent state or upregulation of lineage commitment programs. We integrate lincRNAs into the molecular circuitry of ES cells and show that lincRNA genes are regulated by key transcription factors and that lincRNA transcripts bind to multiple chromatin regulatory proteins to affect shared gene expression programs. Together, the results demonstrate that lincRNAs have key roles in the circuitry controlling ES cell state.Broad InstituteHarvard UniversityNational Human Genome Research Institute (U.S.)Merkin Family Foundation for Stem Cell Researc

Long non-coding RNAs: spatial amplifiers that control nuclear structure and gene expression

Over the past decade, it has become clear that mammalian genomes encode thousands of long non-coding RNAs (lncRNAs), many of which are now implicated in diverse biological processes. Recent work studying the molecular mechanisms of several key examples — including Xist, which orchestrates X chromosome inactivation — has provided new insights into how lncRNAs can control cellular functions by acting in the nucleus. Here we discuss emerging mechanistic insights into how lncRNAs can regulate gene expression by coordinating regulatory proteins, localizing to target loci and shaping three-dimensional (3D) nuclear organization. We explore these principles to highlight biological challenges in gene regulation, in which lncRNAs are well-suited to perform roles that cannot be carried out by DNA elements or protein regulators alone, such as acting as spatial amplifiers of regulatory signals in the nucleus

Characterization of Transcription Start Sites of Putative Non-coding RNAs by Multifaceted Use of Massively Paralleled Sequencer

On the basis of integrated transcriptome analysis, we show that not all transcriptional start site clusters (TSCs) in the intergenic regions (iTSCs) have the same properties; thus, it is possible to discriminate the iTSCs that are likely to have biological relevance from the other noise-level iTSCs. We used a total of 251 933 381 short-read sequence tags generated from various types of transcriptome analyses in order to characterize 6039 iTSCs, which have significant expression levels. We analyzed and found that 23% of these iTSCs were located in the proximal regions of the RefSeq genes. These RefSeq-linked iTSCs showed similar expression patterns with the neighboring RefSeq genes, had widely fluctuating transcription start sites and lacked ordered nucleosome positioning. These iTSCs seemed not to form independent transcriptional units, simply representing the by-products of the neighboring RefSeq genes, in spite of their significant expression levels. Similar features were also observed for the TSCs located in the antisense regions of the RefSeq genes. Furthermore, for the remaining iTSCs that were not associated with any RefSeq genes, we demonstrate that integrative interpretation of the transcriptome data provides essential information to specify their biological functions in the hypoxic responses of the cells