Genetics of ocular disease Part 1: Basic concepts: cells, chromosomes and inheritance

This series of articles describes the basic elements of genetics necessary to understand the new advances and the impact these advances will have on the study and treatment of ocular disease. The first article describes the patterns of inheritance of human characteristics, how they are transmitted between the generations and the structure of chromosomes.

In the name of the father, son, and grandson:succession patterns and the Kim dynasty

This paper seeks to understand North Korea’s Kim Il Sung to Kim Jong Il and Kim Jong Il to Kim Jong Un’s hereditary transition by proposing a comparative analysis of several dictatorship families. The paper utilizes totalitarian successions in Nicaragua with García and Debayle, in Haiti with the Duvalier family, in Syria with the al-Assads, in Azerbaijan with the Aliyevs, in Congo with the Kabilas in order to draw parallels and difference with the North Korea. Eventually, North Korea’s control over information and its management of myths are highlighted as factors that have enabled the country’s hereditary transition, though new patterns of domestic governance might lead to a different political environment over the Korean peninsula.

Inheritance of the CENP-A chromatin domain is spatially and temporally constrained at human centromeres.

BACKGROUND: Chromatin containing the histone variant CENP-A (CEN chromatin) exists as an essential domain at every centromere and heritably marks the location of kinetochore assembly. The size of the CEN chromatin domain on alpha satellite DNA in humans has been shown to vary according to underlying array size. However, the average amount of CENP-A reported at human centromeres is largely consistent, implying the genomic extent of CENP-A chromatin domains more likely reflects variations in the number of CENP-A subdomains and/or the density of CENP-A nucleosomes within individual subdomains. Defining the organizational and spatial properties of CEN chromatin would provide insight into centromere inheritance via CENP-A loading in G1 and the dynamics of its distribution between mother and daughter strands during replication. RESULTS: Using a multi-color protein strategy to detect distinct pools of CENP-A over several cell cycles, we show that nascent CENP-A is equally distributed to sister centromeres. CENP-A distribution is independent of previous or subsequent cell cycles in that centromeres showing disproportionately distributed CENP-A in one cycle can equally divide CENP-A nucleosomes in the next cycle. Furthermore, we show using extended chromatin fibers that maintenance of the CENP-A chromatin domain is achieved by a cycle-specific oscillating pattern of new CENP-A nucleosomes next to existing CENP-A nucleosomes over multiple cell cycles. Finally, we demonstrate that the size of the CENP-A domain does not change throughout the cell cycle and is spatially fixed to a similar location within a given alpha satellite DNA array. CONCLUSIONS: We demonstrate that most human chromosomes share similar patterns of CENP-A loading and distribution and that centromere inheritance is achieved through specific placement of new CENP-A near existing CENP-A as assembly occurs each cell cycle. The loading pattern fixes the location and size of the CENP-A domain on individual chromosomes. These results suggest that spatial and temporal dynamics of CENP-A are important for maintaining centromere identity and genome stability.

Epigenetic Basis of Centromere Maintenance and Inheritance

Centromeres are essential chromosomal loci at which kinetochore formation occurs for spindle fiber attachment during mitosis and meiosis, guiding proper segregation of chromosomes. In humans, centromeres are located at large arrays of alpha satellite DNA, contributing to but not defining centromere function. The histone variant CENP-A assembles at alpha satellite DNA, epigenetically defining the centromere. CENP-A containing chromatin exists as an essential domain composed of blocks of CENP-A nucleosomes interspersed with blocks of H3 nucleosomes, and is surrounded by pericentromeric heterochromatin. In order to maintain genomic stability, the CENP-A domain is propagated epigenetically over each cell division; disruption of propagation is associated with chromosome instabilities such as aneuploidy, found in birth defects and in cancer.

The CENP-A chromatin domain occupies 30-45% of the alpha satellite array, varying in genomic distance according to the underlying array size. However, the molecular mechanisms that control assembly and organization of CENP-A chromatin within its genomic context remain unclear. The domain may shift, expand, or contract, as CENP-A is loaded and dispersed each cell cycle. We hypothesized that in order to maintain genome stability, the centromere is inherited as static chromatin domains, maintaining size and position within the pericentric heterochromatin. Utilizing stretched chromatin fibers, I found that CENP-A chromatin is limited to a sub-region of the alpha satellite array that is fixed in size and location through the cell cycle and across populations.

The average amount of CENP-A at human centromeres is largely consistent, implying that the variation in size of CENP-A domains reflects variations in the number of CENP-A subdomains and/or the density of CENP-A nucleosomes. Multi-color nascent protein labeling experiments were utilized to examine the distribution and incorporation of distinct pools of CENP-A over several cell cycles. I found that in each cell cycle there is independent CENP-A distribution, occurring equally between sister centromeres across all chromosomes, in similar quantities. Furthermore, centromere inheritance is achieved through specific placement of CENP-A, following an oscillating pattern that fixes the location and size of the CENP-A domain. These results suggest that spatial and temporal dynamics of CENP-A are important for maintaining centromere and genome stability.

Mineralogical (bulk rock and clay fraction) and stable isotope composition (d13C, d18O) of Aptian deposits of the Bir Oum Ali succession, central Tunisia

Alternations between siliciclastic, carbonate and evaporitic sedimentary systems, as recorded in the Aptian mixed succession of southern Tunisia, reflect profound palaeoceanographic and palaeoclimatic changes in this area of the southern Tethyan margin. The evolution from Urgonian-type carbonates (Berrani Formation, lower Aptian) at the base of the series, to intervals dominated by gypsum or detrital deposits in the remainder of the Aptian is thought to result from the interplay between climate change and tectonic activity that affected North Africa. Based on the evolution of clay mineral assemblages, the early Aptian is interpreted as having been dominated by slightly humid conditions, since smectitic minerals are observed. Near the early to late Aptian boundary, the onset of a gypsiferous sedimentation is associated with the appearance of palygorskite and sepiolite, which supports the installation of arid conditions in this area of the southern Tethyan margin. The evaporitic sedimentation may have also been promoted by the peculiar tectonic setting of the Bir Oum Ali area during the Aptian, where local subsidence may have been tectonically enhanced linked to the opening of northern and central Atlantic. Stress associated with the west and central African rift systems may have triggered the development of NW-SE, hemi-graben structures. Uplifted areas may have constituted potential new sources for clastic material that has been subsequently deposited during the late Aptian. Chemostratigraphic (d13C) correlation of the Bir Oum Ali succession with other peri-Tethyan regions complements biostratigraphic findings, and indicates that a potential expression of the Oceanic Anoxic Event (OAE) 1a may be preserved in this area of Tunisia. Although the characteristic negative spike at the base of this event is not recognized in the present study, a subsequent, large positive excursion with d13C values is of similar amplitude and absolute values to that reported from other peri-Tethyan regions, thus supporting the identification of isotopic segments C4-C7 of the OAE1a. The absence of the negative spike may be linked to either non preservation or non deposition: the OAE1a occurred in a global transgressive context, and since the Bir Oum Ali region was located in the innermost part of the southern Tethyan margin during most of the Aptian, stratigraphic hiatuses may have been longer than in other regions of the Tethys. This emphasizes the importance of integrating several stratigraphic disciplines (bio-, chemo- and sequence stratigraphy) when performing long-distance correlation.

Strontium isotopes and sedimentology of a marine Triassic succession (upper Ladinian) of the westernmost Tethys, Spain

Chemical Stratigraphy, or the study of the variation of chemical elements within sedimentary sequences, has gradually become an experienced tool in the research and correlation of global geologic events. In this paper 87Sr/ 86Sr ratios of the Triassic marine carbonates (Muschelkalk facies) of southeast Iberian Ranges, Iberian Peninsula, are presented and the representative Sr-isotopic curve constructed for the upper Ladinian interval. The studied stratigraphic succession is 102 meters thick, continuous, and well preserved. Previous paleontological data from macro and micro, ammonites, bivalves, foraminifera, conodonts and palynological assemblages, suggest a Fassanian-Longobardian age (Late Ladinian). Although diagenetic minerals are present in small amounts, the elemental data content of bulk carbonate samples, especially Sr contents, show a major variation that probably reflects palaeoenvironmental changes. The 87Sr/86Sr ratios curve shows a rise from 0.707649 near the base of the section to 0.707741 and then declines rapidly to 0.707624, with a final values rise up to 0.70787 in the upper part. The data up to meter 80 in the studied succession is broadly concurrent with 87Sr/86Sr ratios of sequences of similar age and complements these data. Moreover, the sequence stratigraphic framework and its key surfaces, which are difficult to be recognised just based in the facies analysis, are characterised by combining variations of the Ca, Mg, Mn, Sr and CaCO3 contents

Massachusetts College of Art and Design y Universidad de Cuenca. Acuerdo de Intercambio Estudiantil. Memorándum de Acuerdo entre Massachusetts College of Art and Design (Massart), Boston, Massachusetts, U:S:A. y la Universidad de Cuenca, Ecuador

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Family Business Succession in Austria – Satisfaction and the Incumbent-successor Relationship

The transfer of businesses contributes to the dynamics and the development of the economy in Austria. Successful transfers generate numerous positive impacts. Securing both employment and investment, creating new jobs and stimulating growth are some of these effects. Failed transfers can contribute to negative effects, including the loss of jobs and an economic slowdown. Over recent years the number of business handovers in Austria has been rising. The forecasts show that this number will remain high over the next few years. Between 2015 and 2024 more than 42,000 economically sound SMEs will face the challenge of finding an appropriate successor. This means that 26 % of all Austrian SMEs (excluding one-person businesses) and 29 % of all employees in these companies will be affected. The aim of this paper is to provide a multi-faceted discussion of the relevance of affective components in family business transfers. A “good” relationship between the successor and the departing owner fosters the success of a transfer. This relationship involves, among others, the willingness to share relevant information, openness and respect. The satisfaction (with the completed business transfer) is closely interrelated with the relationship between the successor and the departing owner. Consequently, we can assume that affective and emotional components can indeed shape the success of business transfers. Based on that, new future research opportunities are outlined.

Financial Characteristics of Family Businesses and Financial Aspects of Succession

Family businesses are special in many respects. By examining their financial characteristics one can come to unique conclusions/results. This paper explores the general characteristics of the financial behaviour of family businesses, presents the main findings of the INSIST project’s company case studies concerning financing issues and strategies, and intends to identify the financial characteristics of company succession. The whole existence of family businesses is characterized by a duality of the family and business dimensions and this remains the case in their financial affairs. The financial decisions in family businesses (especially SMEs) are affected by aspects involving a duality of goals rather than exclusively profitability, the simultaneous presence of family and business financial needs, and the preferential handling of family needs at the expense of business needs (although it has to be said that there is evidence of family investments being postponed for the sake of business, too. Family businesses, beyond their actual effectiveness, are guided by individual goals like securing living standards, ensuring workplaces for family members, stability of operation, preservation of the company’s good reputation, and keeping the company’s size at a level that the immediate family can control and manage. The INSIST project’s company case studies revealed some interesting traits of family business finances like the importance of financial support from the founder’s family during the establishment of the company, the use of bootstrapping techniques, the financial characteristics of succession, and the role of family members in financial management.

Managing Succession and Knowledge Transfer in Family Businesses: Lessons from a Comparative Research

The most natural mode of family firm succession is the intergenerational ownership transfer. Statistical evidence, however, suggests that in most cases the succession process fails. There can be several reasons as a lot of personal, emotional and structural factors can act as an inhibitor to succession. The effectiveness of the implementation of any succession strategy is strongly dependent on the efficiency of intergenerational knowledge transfer, which is related to the parties’ absorptive capacity and willingness to learn. The paper is based on the experiences learned from the INSIST project. In the framework of the project different aspects of family business succession have been investigated in three participating countries (Hungary, Poland and the United Kingdom). The aim of the paper is to identify the patterns of management, succession, knowledge transfer and learning in family businesses. Issues will be examined in detail such as the succession strategies of companies investigated and the efforts family businesses and their managers make in order to harmonize family goals (such as emotional stability, harmony, and reputation) with business- related objectives (e.g. survival, growth or profitability).