The conserved FLLL motif is key for glycoprotein expression. We introduced a panel of double point mutations within this FLLL motif in order to determine whether any one amino acid was key for a processed and mature GP complex. The AALL GPC was defective in its ability to allow posttranslational modifications and revealed a dominant negative maturation phenotype, since the addition of wild-type SSP did not rescue glycosylated glycoprotein expression or processing (Fig. 4A; see Fig. S2 in the supplemental material). The ALLA GPC supported precursor GP posttransla- tional modifications but was defective in producing a processed GP2 subunit. The ALLA GPC produced a cleavage GP2 subunit with the in trans addition of wild-type SSP (Fig. 4B). The FALA GPC retaining the conserved phenylalanine encoded by all known rodent arenaviruses and resulted in a reduced level of GP2 cleav- age from the precursor GPC, while levels of GP2 were increased with the cotransfection of the wild-type SSP. Densitometry anal- ysis of the FALA GPC and wild-type SSP cotransfection, from three independent replicates, resulted in an overall increase in the amount of GPC processed to yield the GP2 subunit, while the representative Western blot in Fig. 4A does not highlight this slight rescue in GP2 processing (Fig. 4B). The YALL GPC resulted in the highest percentage of processed glycoprotein of all SSP mu- tants we analyzed, though not at the level of the wild-type GP2 cleavage. Interestingly, the cotransfection of the wild-type SSP with YALL GPC resulted in the reduced expression of the total glycoprotein complex. The final variant we examined, YLAL GPC, was toxic to transfected cells and consistently yielded low levels of detectable glycoprotein. Overall, double point mutations within this conserved SSP motif indicate that this entire motif, and not one residue in particular, plays a dominant role in downstream processes that mediate processing of the precursor into mature glycoprotein subunits.
Figure 6.—A summary of the regulatory elements controlling the transcriptional regulation of Gld and a model of their interac- tions. (Top) Gld regulatory ele- ments controlling Gld tissue-spe- cific regulation are shown in the first row. A plus (⫹) indicates that the element is required to activate expression in the organ shown in the first column. A minus (⫺) in- dicates that the element blocks expression. With the exception of activation of expression in the semi- nal receptacle and repression of oviduct expression, the activity of the SREC complex is composed of the three reproductive organ enhancers, EOE, BCUE, and BMSE, and their interaction among them- selves and with the Gld promoter elements. (Bottom) Model of the interaction of the Gld intronic en- hancers, silencers, the proximal promoter elements, and the pro- moter. The locations of these ele- ments have been mapped as de- scribed herein with the exception of the SEXS element which is only known to map within the 17.5-kb fragment defining the total Gld gene.
Background: Models of cognition propose a hierarchical structure for human cognitive processes, in which the sequences of human action are organized into parts or subunits of analysis that can be grouped into progressively more complex, inclusive higher-order functions. This organizational structure from partial to whole may be refl ected in the neural representations that underlie human behaviour, and in its genetic underpinnings. The objective of the present study was to explore a putative hierarchical organization of the genetic infl uences underlying cognitive domains. Method: Thirty four studies of the heritability of cognition on population-based samples were reviewed, which included measures of intelligence, verbal and performance abilities, memory, working memory and processing speed. Results: Specifi c cognitive domains showed diverse proportions of genetic underpinnings such that higher- order cognitive functions present high heritability estimates, whereas lower-order functions respond to small/moderate heritability estimates. Conclusions: Based on current understanding of the developmental processes of the neurobiological substrates of human cognition, the genetic contributions to cognitive abilities seem to be organized in line with the ontogenic maturation of the brain. We discuss the large genetic control of the combinatory capacity of basic cognitive functions, and its interaction with environmental infl uences.
Overcoming complex problems in evolutionary processes will be contributing to reducing transaction costs, and economizing on transaction costs would be a byproduct of solving more fundamental problems of strategic uncertainty. However, reducing the focus to quantitative marginal static equilibration and ‘optimization’ of transaction costs as the unique objective of action, prevents a deeper analysis, including analysis of the causes and sources of transaction costs, particularly when agents are facing coordination and dilemma problems. The perspective remains reduced to one dimension in terms of both the goal indicator (i.e., transaction costs) and resulting organizational forms. Comparative marginal transaction costs and related choice of organizational form determine the degree of vertical integration, or relative lengths of the value-added chains inside vs. outside hierarchy, i.e., the relative size of the firm vs. the market. This appears to fall short of tackling a number of questions that have surged in the real world.
These self-organizing dissipative structures are both persistent and nonlinear. The persistent nature of these dissipative structures could be demonstrated by the complex processes surrounding the chemical reactions involving autocatalytic hyper cycles (Eigen and Schuster, 1979). In autocatalytic hyper cycles an open system that is exchanging mater and energy from the environment such as a continuous feed chemical reactor far away from equilibrium, there can be produced a class of microstate autocatalytic agent that will create temporal oscillations and dissipative structures and it will help furthers the autocatalytic process. This progress of the autocatalytic reaction is controlled by a positive autocatalytic feedback loop where the activator agent or species enforces its own changes which later are counterbalanced by some kind of parallel inhibitory process resulting in a system maintained at far from equilibrium but still delivering the desired chemical kinetics. During this autocatalytic process dissipative entropic structures are formed within the system over space and time as inhibitory system effects diffuse through a complex oscillatory system. Argued to be sensitive to initial condition and the path of their creation, these autocatalytic disruptive structures are able to generate dynamic system behaviour ranging from stable order to complexorganization under chaos or edge of chaos (McKelvey, 1999b). The nonlinearity of dissipative structures is demonstrated by their tendency to either create substantial explosion or a sudden crash of structures. Many such complex, dynamic, self- organizing dissipative structures, similar to the ones generated in autocatalytic process, have been identified in natural phenomenon (Cramer, 1993; Kaye, 1993; Mainzer, 1997), and have been hypothesized to be applicable to the context of firms and organizations (Zimmerman and Hurst, 1993; Levy, 1994; Thiétart and Forgues, 1995; Stacey, 1996).
This tests the sub-hypothesis by using stepwise regression. Chart (4) show the results between the dimensions of the organization agility ( HR agility, IT agility, and Innovation agility) and organizational performance; it's important to comprehend whether the dimensions of organizational agility affects organizational performance or not, and thus, the percentage of the organizational agility dimensions in the recession curve model indicate a partial regression coefficient (Beta) for each dimension. Chart (4) displays that the most effective dimensions are: HR Agility (β=0.371), and Information technology agility (β=0.223), where there was not any effect for the Innovation Agility on the organizational performance.
Given the role of AP-1 in MT organization, we also studied its role in septin localization. Septins are less well characterized GTP-binding proteins, which form hetero-polymers associat- ing into higher order structures, and are thought to play a central role in the spatial regulation and coordination of the actin and MT networks in most eukaryotes (Mostowy and Cossart 2012; Spiliotis 2018). In A. nidulans, ﬁve septins have been under investigation, the four core septins AspA– D, which form hetero-polymers appearing in various shapes, including spots, rings, and ﬁlaments, and a ﬁfth septin of currently unknown function, AspE, not involved in the het- ero-polymer and appearing as dense cortical spots at the proximity of the plasma membrane (Hernández-Rodríguez and Momany 2012; Hernández-Rodríguez et al. 2014; Momany and Talbot 2017). Figure 6E shows that upon AP-1 repression, hetero-polymer forming core septins AspB, AspC, and AspD appear less in the form of ﬁlamentous struc- tures, while distinct bright cortical spots tend to accumulate at the hyphal periphery, several of which possibly mark posi- tions of new septa, in agreement with increased numbers of septa observed in the absence of AP-1. Interestingly, AspE, appears largely unaffected with the exception of the more frequent appearance of septa. All the above observations are in agreement with many other previously described phe- notypes associating with AP-1 repression and suggest an im- plication of AP-1 in the processes regulating septin polymer formation. Noticeably, proper endosomal trafﬁcking of
The most deadly of the human malaria parasites, Plasmodium falciparum, has different stages special- ized for invasion of hepatocytes, erythrocytes, and the mosquito gut wall. In each case, host cell invasion is powered by an actin-myosin motor complex that is linked to an inner membrane complex (IMC) via a membrane anchor called the glideosome-associated protein 50 (PfGAP50). We generated P. falciparum transfectants expressing green fluorescent protein (GFP) chimeras of PfGAP50 (PfGAP50-GFP). Using immunoprecipitation and fluorescence photobleaching, we show that C-terminally tagged PfGAP50-GFP can form a complex with endogenous copies of the linker protein PfGAP45 and the myosin A tail domain-interacting protein (MTIP). Full-length PfGAP50-GFP is located in the endoplasmic reticulum in early-stage parasites and then redistributes to apical caps during the formation of daughter merozoites. In the final stage of schizogony, the PfGAP50-GFP profile extends further around the merozoite surface. Three-dimensional (3D) structured illumination microscopy reveals the early-stage IMC as a doubly punctured flat ellipsoid that separates to form claw-shaped apposed structures. A GFP fusion of PfGAP50 lacking the C-terminal membrane anchor is misdirected to the parasitophorous vacuole. Replacement of the acid phosphatase homology domain of PfGAP50 with GFP appears to allow correct trafficking of the chimera but confers a growth disadvantage.
The calculation of unknown variables (2) and parameter according to conditions that are formalized by inequalities (3-11), it is recommended to perform optimization task, ensuring minimum or maximum of selected criteria of decision quality of structural self-organization. The main requirements to the optimal criteria on the one hand should be physics of the task, i.e., task of channel distribution in the mesh-network and on the other hand should be the abilities to obtain solutions that can be practically realized. This way, the input conditions and the task itself must not be too complicated. For its solution the effective method must be developed.
Fig.·5. Optical responses in the antennal lobe (AL) elicited by electrical stimulation of the medial nerve (MN) and the lateral nerve (LN). (A) Real image of the moth brain (boxed area of inset). The boxed area in the schematic drawing corresponds to the MOS-type image sensor used by optical recording. Scale bar, 500·µm. OL, optic lobe; PC, protocerebrum. (B) Optical responses in the AL. All optical images were superimposed on the bright real image of the AL. Consistent response patterns in the macroglomerular complex (MGC) were evoked by the electrical stimulation of the medial nerve (MN) or the lateral nerve (LN). The pattern was initially a depolarization of the antennal nerve (AN; 3.6–7.2·ms after the onset of the stimulation) and, subsequently, a depolarization of the MGC (4.8–9.6·ms). At 7.2·ms from the stimulus of the MN, the area strongly (>0.4% of the background fluorescence) responding to stimulation of the MN was restricted to the medial half of the MGC. By contrast, the area strongly (>0.4% of the background fluorescence) responding to stimulation of the LN was restricted to the lateral half of the MGC. (C) Time course of the optical signals in the AL evoked by stimulation of the MN (upper panel) and the LN (lower panel). The optical signal was calculated by averaging signals recorded in areas that had a response of >0.3% (– ∆ F/F) at 7.2·ms from the stimulus onset and filtered at 246·Hz (F c ). The response, evoked in the MGC, had a peak at 7.2·ms after the stimulus onset. The response had another
Botryococcus braunii is a colonial green alga whose cells associate via a complex extracellular matrix (ECM) and produce prodi- gious amounts of liquid hydrocarbons that can be readily converted into conventional combustion engine fuels. We used quick- freeze deep-etch electron microscopy and biochemical/histochemical analysis to elucidate many new features of B. braunii cell/ colony organization and composition. Intracellular lipid bodies associate with the chloroplast and endoplasmic reticulum (ER) but show no evidence of being secreted. The ER displays striking fenestrations and forms a continuous subcortical system in di- rect contact with the cell membrane. The ECM has three distinct components. (i) Each cell is surrounded by a fibrous ␤-1, 4- and/or ␤ -1, 3-glucan-containing cell wall. (ii) The intracolonial ECM space is filled with a cross-linked hydrocarbon network permeated with liquid hydrocarbons. (iii) Colonies are enclosed in a retaining wall festooned with a fibrillar sheath dominated by arabinose-galactose polysaccharides, which sequesters ECM liquid hydrocarbons. Each cell apex associates with the retaining wall and contributes to its synthesis. Retaining-wall domains also form “drapes” between cells, with some folding in on them- selves and penetrating the hydrocarbon interior of a mother colony, partitioning it into daughter colonies. We propose that re- taining-wall components are synthesized in the apical Golgi apparatus, delivered to apical ER fenestrations, and assembled on the surfaces of apical cell walls, where a proteinaceous granular layer apparently participates in fibril morphogenesis. We further propose that hydrocarbons are produced by the nonapical ER, directly delivered to the contiguous cell membrane, and pass across the nonapical cell wall into the hydrocarbon-based ECM.
Here, we show that the fundamental discrepancy between models and empirical measurements is rooted in a previously disregarded, yet generic feature of many real networks: their hierarchical topology. Indeed, many networks are fundamen- tally modular: one can easily identify groups of nodes that are highly interconnected with each other, but have only a few or no links to nodes outside of the group to which they belong to. In society, such modules represent groups of friends or co-workers 关 17 兴 ; in the WWW, they denote com- munities with shared interests 关 18,19 兴 ; in the actor network, they characterize specific genres or simply individual mov- ies. Some groups are small and tightly linked, others are larger and somewhat less interconnected. This clearly iden- tifiable modular organization is at the origin of the high clus- tering coefficient seen in many real networks. Yet, models reproducing the scale-free property of real networks 关 1,2 兴 distinguish nodes based only on their degree, and are blind to node characteristics that could lead to a modular topology.
One interesting thing about the Darul Arqam was its ability to appeal to the urban Malays although its approach is retrospective. In a study done by Kamarulnizam (1998), he found that this was due to several reasons. The first is the charismatic leadership of Ustaz Ashaari Muhammad. Secondly, the Darul Arqam guides its members back to basics of Islam, preaching on the importance of one’s relationship with Allah (hablum minaAllah) and self correction. Thirdly, as does the Jamaat Tabligh, the Darul Arqam does not use jargons but simple concepts of iman and taqwa which is easy to follow and understand. Many of its member of the Council of Syuyuks (Syeikhs) are educated and urban-based Malays although there were accusations of kinship domination. The reason being, that Ustaz Ashaari’s sons and son in law were among the high ranking syeikhs of the Darul Arqam. The Darul Arqam also tries to establish its learning activities through classes, sermons, audio tapes, video tapes and some publications, however since it is not a formal organization and does not have official membership, it is quite difficult to see its learning activities in the eyes of a formal organizational learning perspective as purpoted in the LO and OL concept.
The general model of OD, being an integration of the other three models, shares in their strengths, whilst attempting to bridge the gaps in these approaches. Its strengths lie in the following: it fosters collaborative work between the change agent and client, and focuses on both problem identification and development of new and positive ideas and best practices. It also targets change at the organizational (e.g. strategic and structural change), group (e.g. departmental behaviours and norms) and individual (e.g. job descriptions) levels. It emphasizes cycles of research and action until the desired change has been achieved. It also encourages research to promote problem identification/defining. In addition, the general OD model informs change agents not only about the stages of change, but also, provide clear guidance on the sets of activities necessary at each stage to move the organization to the desired state (Cummings & Worley, 2006; Lacey, 1995).
Canadian Journal of Economics, Economics Bulletin, Economics of Innovation and New Technology, European Economic Review, Financial Management, International Journal of Industrial Organization, Journal of Business Venturing, Journal of the European Economic Association, Journal of Economics and Management Strategy, Journal of Empirical Finance, Journal of Industrial Economics, Journal of Labor Economics, Journal of Law Economics and Organization, Journal of Political Economy, Journal of Public Economic Theory, Management Science, Oxford Economic Papers, Public
Executive function; Organization
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