The Impact of Socialist Imprinting and Search for Knowledge on Resource Change: An Empirical Study of Firms in Lithuania

In this paper we examine how firms change their resources in response to exogenous shocks in their business environment. Building on core ideas from the literatures on organizational imprinting and firm resources, we suggest that founding conditions differentially imprint firm resources. These initial imprinting differentials in turn influence the search for knowledge required to adapt or change firm resources in the face of external change in their business environment. We also suggest that the level of imprinting and the location of search independently and jointly influence the success with which firms are able to change their resources. We use survey-based data from a set of firms in Central Europe that experienced an exogenous shock in 1989-1991 to test our arguments. We develop a measure of pre-shock imprinting (called socialist imprinting) on resources and use it to predict where firms will search for knowledge to undertake change in the post-shock period and how successful that change will be. We find that the level of socialist imprinting influences the search location for knowledge to change key resources and activities following the shock. In terms of the success of change undertaken, we see that distant search for knowledge is positively linked to it. We also observe that the level of imprinting and search location jointly impact the success of change; for resources with higher socialist imprinting, distant search was more effective than local search. This research makes three important contributions in the context of existing research on organizational imprinting and firm level change. One, it focuses on firm-level resources to examine the impact of imprinting. Two, we examine how differences in resource level imprinting influence the search for new knowledge required to transform these resources. Three, we demonstrate that the interaction between the level of imprinting and the nature of search has important influences on firm performance. Our findings also provide insights to practitioners and policy makers who deal with firms in transitional economies. Practitioners can better understand how to undertake firm level change more effectively in the context of sudden exogenous shock. For policy makers, both of domestic and international institutions, understanding the change process can help formulate assistance programs more effectively.http://deepblue.lib.umich.edu/bitstream/2027.42/39830/3/wp446.pd

Retrotransposon silencing by DNA methylation can drive mammalian genomic imprinting

Among mammals, only eutherians and marsupials are viviparous and have genomic imprinting that leads to parent-of-origin-specific differential gene expression. We used comparative analysis to investigate the origin of genomic imprinting in mammals. PEG10 (paternally expressed 10) is a retrotransposon-derived imprinted gene that has an essential role for the formation of the placenta of the mouse. Here, we show that an orthologue of PEG10 exists in another therian mammal, the marsupial tammar wallaby (Macropus eugenii), but not in a prototherian mammal, the egg-laying platypus (Ornithorhynchus anatinus), suggesting its close relationship to the origin of placentation in therian mammals. We have discovered a hitherto missing link of the imprinting mechanism between eutherians and marsupials because tammar PEG10 is the first example of a differentially methylated region (DMR) associated with genomic imprinting in marsupials. Surprisingly, the marsupial DMR was strictly limited to the 5′ region of PEG10, unlike the eutherian DMR, which covers the promoter regions of both PEG10 and the adjacent imprinted gene SGCE. These results not only demonstrate a common origin of the DMR-associated imprinting mechanism in therian mammals but provide the first demonstration that DMR-associated genomic imprinting in eutherians can originate from the repression of exogenous DNA sequences and/or retrotransposons by DNA methylation

Telomeric NAP1L4 and OSBPL5 of the KCNQ1 cluster, and the DECORIN gene are not imprinted in human trophoblast stem cells

Background: Genomic imprinting of the largest known cluster, the Kcnq1/KCNQ1 domain on mChr7/hChr11, displays significant differences between mouse and man. Of the fourteen transcripts in this cluster, imprinting of six is ubiquitous in mice and humans, however, imprinted expression of the other eight transcripts is only found in the mouse placenta. The human orthologues of the latter eight transcripts are biallelically expressed, at least from the first trimester onwards. However, as early development is less divergent between species, placental specific imprinting may be present in very early gestation in both mice and humans. Methodology/Principal Findings: Human embryonic stem (hES) cells can be differentiated to embryoid bodies and then to trophoblast stem (EB-TS) cells. Using EB-TS cells as a model of post-implantation invading cytotrophoblast, we analysed allelic expression of two telomeric transcripts whose imprinting is placental specific in the mouse, as well as the ncRNA KCNQ1OT1, whose imprinted expression is ubiquitous in early human and mouse development. KCNQ1OT1 expression was monoallelic in all samples but OSBPL5 and NAP1L4 expression was biallelic in EB-TS cells, as well as undifferentiated hES cells and first trimester human fetal placenta. DCN on hChr12, another gene imprinted in the mouse placenta only, was also biallelically expressed in EB-TS cells. The germline maternal methylation imprint at the KvDMR was maintained in both undifferentiated hES cells and EB-TS cells. Conclusions/Significance: The question of placental specific imprinting in the human has not been answered fully. Using a model of human trophoblast very early in gestation we show a lack of imprinting of two telomeric genes in the KCNQ1 region and of DCN, whose imprinted expression is placental specific in mice, providing further evidence to suggest that humans do not exhibit placental specific imprinting. The maintenance of both differential methylation of the KvDMR and monoallelic expression of KCNQ1OT1 indicates that the region is appropriately regulated epigenetically in vitro. Human gestational load is less than in the mouse, resulting in reduced need for maternal resource competition, and therefore maybe also a lack of placental specific imprinting. If genomic imprinting exists to control fetal acquisition of maternal resources driven by the placenta, placenta-specific imprinting may be less important in the human than the mouse

The long non-coding RNA Kcnq1ot1 controls maternal p57 expression in muscle cells by promoting H3K27me3 accumulation to an intragenic MyoD-binding region

BACKGROUND: The cell-cycle inhibitor p57kip2 plays a critical role in mammalian development by coordinating cell proliferation and differentiation in many cell types. p57kip2 expression is finely regulated by several epigenetic mechanisms, including paternal imprinting. Kcnq1ot1, a long non-coding RNA (LncRNA), whose gene maps to the p57Kip2 imprinting domain, is expressed exclusively from the paternal allele and participates in the cis-silencing of the neighboring imprinted genes through chromatin-level regulation. In light of our previous evidence of a functional interaction between myogenic factors and imprinting control elements in the regulation of the maternal p57Kip2 allele during muscle differentiation, we examined the possibility that also Kcnq1ot1 could play an imprinting-independent role in the control of p57Kip2 expression in muscle cells. RESULTS: We found that Kcnq1ot1 depletion by siRNA causes the upregulation of the maternal and functional p57Kip2 allele during differentiation, suggesting a previously undisclosed role for this LncRNA. Consistently, Chromatin Oligo-affinity Precipitation assays showed that Kcnq1ot1 physically interacts not only with the paternal imprinting control region of the locus, as already known, but also with both maternal and paternal alleles of a novel p57Kip2 regulatory region, located intragenically and containing two binding sites for the muscle-specific factor MyoD. Moreover, chromatin immunoprecipitation assays after Kcnq1ot1 depletion demonstrated that the LncRNA is required for the accumulation of H3K27me3, a chromatin modification catalyzed by the histone-methyl-transferase EZH2, at the maternal p57kip2 intragenic region. Finally, upon differentiation, the binding of MyoD to this region and its physical interaction with Kcnq1ot1, analyzed by ChIP and RNA immunoprecipitation assays, correlate with the loss of EZH2 and H3K27me3 from chromatin and with p57Kip2 de-repression. CONCLUSIONS: These findings highlight the existence of an imprinting-independent role of Kcnq1ot1, adding new insights into the biology of a still mysterious LncRNA. Moreover, they expand our knowledge about the molecular mechanisms underlying the tight and fine regulation of p57Kip2 during differentiation and, possibly, its aberrant silencing observed in several pathologic conditions

Differential and Temporal Immunomodulation of alpha4 Integrins on CD4+ Memory Cells by Bordetella pertussis and Bordetella parapertussis

Pertussis, caused by Bordetella pertussis (B. pertussis), is reemerging worldwide due to vaccine inefficacy. The hallmarks of infection are extreme lymphocytosis and delayed recovery, which are partially associated with pertussis toxin. Lymphocytes migrate to infected tissues using trafficking receptors. Specific combinations of these lymphocyte trafficking receptors are identified for skin and gut but are not well established for lung. This study focused on the effect of pertussis toxin on lung-associated trafficking receptors and tested the hypothesis that pertussis toxin alters dendritic cell imprinting of lung trafficking receptors on T cells, thus delaying resolution of the infection. B. pertussis-infected mice were compared with pertussis toxin-deficient strains. Imprinting of trafficking receptors on allogeneic T cells by dendritic cells derived from Bordetella-infected mice was analyzed by flow cytometry. Mice infected with Bordetella strains showed an increase in mature dendritic cells on day 5 post-infection. Despite their mature phenotype, dendritic cells from B. pertussis infection, were compromised in their ability to imprint lung trafficking receptors on allogenic T cells. These results indicated a pertussis toxin-dependent defect in dendritic cell imprinting of lung trafficking receptors on T cells. In conclusion, this study provides important data for future vaccine development against respiratory pathogens

A global disorder of imprinting in the human female germ line

Imprinted genes are expressed differently depending on whether they are carried by a chromosome of maternal or paternal origin. Correct imprinting is established by germline-specific modifications; failure of this process underlies several inherited human syndromes. All these imprinting control defects are cis-acting, disrupting establishment or maintenance of allele-specific epigenetic modifications across one contiguous segment of the genome. In contrast, we report here an inherited global imprinting defect. This recessive maternal-effect mutation disrupts the specification of imprints at multiple, non-contiguous loci, with the result that genes normally carrying a maternal methylation imprint assume a paternal epigenetic pattern on the maternal allele. The resulting conception is phenotypically indistinguishable from an androgenetic complete hydatidiform mole, in which abnormal extra-embryonic tissue proliferates while development of the embryo is absent or nearly so. This disorder offers a genetic route to the identification of trans-acting oocyte factors that mediate maternal imprint establishment

Low-Shot Learning with Imprinted Weights

Human vision is able to immediately recognize novel visual categories after seeing just one or a few training examples. We describe how to add a similar capability to ConvNet classifiers by directly setting the final layer weights from novel training examples during low-shot learning. We call this process weight imprinting as it directly sets weights for a new category based on an appropriately scaled copy of the embedding layer activations for that training example. The imprinting process provides a valuable complement to training with stochastic gradient descent, as it provides immediate good classification performance and an initialization for any further fine-tuning in the future. We show how this imprinting process is related to proxy-based embeddings. However, it differs in that only a single imprinted weight vector is learned for each novel category, rather than relying on a nearest-neighbor distance to training instances as typically used with embedding methods. Our experiments show that using averaging of imprinted weights provides better generalization than using nearest-neighbor instance embeddings.Comment: CVPR 201

Enhanced selectivity of hydrogel-based molecularly imprinted polymers (HydroMIPs) following buffer conditioning.

We have investigated the effect of buffer solution composition and pH during the preparation, washing and re-loading phases within a family of acrylamide-based molecularly imprinted polymers (MIPs) for bovine haemoglobin (BHb), equine myoglobin (EMb) and bovine catalyse (BCat). We investigated water, phosphate buffer saline (PBS), tris(hydroxymethyl)aminomethane (Tris) buffer and succinate buffer. Throughout the study MIP selectivity was highest for acrylamide, followed by N-hydroxymethylacrylamide, and then N-iso-propylacrylamide MIPs. The selectivity of the MIPs when compared with the NIPs decreased depending on the buffer conditions and pH in the order of Tris>PBS>succinate. The Tris buffer provided optimum imprinting conditions at 50mM and pH 7.4, and MIP selectivities for the imprinting of BHb in polyacrylamide increased from an initial 8:1 to a 128:1 ratio. It was noted that the buffer conditions for the re-loading stage was important for determining MIP selectivity and the buffer conditions for the preparation stage was found to be less critical. We demonstrated that once MIPs are conditioned using Tris or PBS buffers (pH7.4) protein reloading in water should be avoided as negative effects on the MIP's imprinting capability results in low selectivities of 0.8:1. Furthermore, acidifying the pH of the buffer solution below pH 5.9 also has a negative impact on MIP selectivity especially for proteins with high isoelectric points. These buffer conditioning effects have also been successfully demonstrated in terms of MIP efficiency in real biological samples, namely plasma and serum

Molecular Bio-imprinting of Biocatalysts

Energy conservation is the cry of the day. Attempts are made all over the world to occupy and use energy reserves. Increased industrialization and mechanization has led to the depletion of natural energy reserves. Its unavoidable to search for renewable sources of energy, which may be not used now but can be used by future generations. We are using the expertise of our ancestors. Thus exploiting the nature and newer techniques in this area would yield the best results. Bio-imprinting is one of those techniques whereby chemical modification is done in order to achieve highly expressed protein which can be stored in its highly active form in the specific solvent