Gene conversions and unequal crossovers between CYP21 (steroid 21-hydroxylase gene) and CYP21P involve different mechanisms.

Most cases of congenital adrenal hyperplasia, the inherited inability to synthesize cortisol, are caused by mutations in the steroid 21-hydroxylase gene (CYP21). Steroid 21-hydroxylase deficiency is unusual among genetic diseases in that approximately 95% of the mutant alleles have apparently been generated by recombination between a normally active gene (CYP21) and a linked pseudogene (CYP21P). Approximately 20% of mutant alleles carry DNA deletions of 30 kb that have presumably been generated by unequal meiotic crossing-over, whereas 75% carry one or more mutations in CYP21 that are normally found in the CYP21P pseudogene. These latter mutations are termed "gene conversions," although the mechanism by which they are generated is not well understood. To assess the frequency at which these different recombination events occur, we have used PCR to detect de novo deletions and gene conversions in matched sperm and peripheral blood leukocyte DNA samples from normal individuals. Deletions with breakpoints in a 100-bp region in intron 2 and exon 3 were detected in sperm DNA samples with frequencies of approximately 1 in 10(5)-10(6) genomes but were never detected in the matching leukocyte DNA. Gene conversions in the same region occur in approximately 1 in 10(3)-10(5) genomes in both sperm and leukocyte DNA. These data suggest that whereas deletions occur exclusively in meiosis, gene conversions occur during both meiosis and mitosis, or perhaps only during mitosis. Thus, gene conversions must occur by a mechanism distinct from unequal crossing-over.

Y chromosome short arm-Sxr recombination in XSxr/Y males causes deletion of Rbm and XY female sex reversal.

We earlier described three lines of sex-reversed XY female mice deleted for sequences believed close to the testes-determining gene (Sry) on the Y chromosome short arm (Yp). The original sex-reversed females appeared among the offspring of XY males that carried the Yp duplication Sxr on their X chromosome. Earlier cytogenetic observations had suggested that the deletions resulted from asymmetrical meiotic recombination between the Y and the homologous Sxr region, but no direct evidence for this hypothesis was available. We have now analyzed the offspring of XSxr/Y males carrying an evolutionarily divergent Mus musculus domesticus Y chromosome, which permits detection and characterization of such recombination events. This analysis has enabled the derivation of a recombination map of Yp and Sxr, also demonstrating the orientation of Yp with respect to the Y centromere. The mapping data have established that Rbm, the murine homologue of a gene family cloned from the human Y chromosome, lies between Sry and the centromere. Analysis of two additional XY female lines shows that asymmetrical Yp-Sxr recombination leading to XY female sex reversal results in deletion of Rbm sequences. The deletions bring Sry closer to Y centromere, consistent with the hypothesis that position-effect inactivation of Sry is the basis for the sex reversal.

Functional haplodiploidy: a mechanism for the spread of insecticide resistance in an important international insect pest.

The coffee berry borer, Hypothenemus hampei, is the most important insect pest of coffee worldwide and has an unusual life history that ensures a high degree of inbreeding. Individual females lay a predominantly female brood within individual coffee berries and because males are flightless there is almost entirely full sib mating. We investigated the genetics associated with this interesting life history after the important discovery of resistance to the cyclodiene type insecticide endosulfan. Both the inheritance of the resistance phenotype and the resistance-associated point mutation in the gamma-aminobutyric acid receptor gene Rdl were examined. Consistent with haplodiploidy, males failed to express and transmit paternally derived resistance alleles. Furthermore, while cytological examination revealed that males are diploid, one set of chromosomes was condensed, and probably nonfunctional, in the somatic cells of all males examined. Moreover, although two sets of chromosomes were present in primary spermatocytes, the chromosomes failed to pair before the single meiotic division, and only one set was packaged in sperm. Thus, the coffee berry borer is "functionally" haplodiploid. Its genetics and life history may therefore represent an interesting intermediate step in the evolution of true haplodiploidy. The influence of this breeding system on the spread of insecticide resistance is discussed.

Crossover and noncrossover recombination during meiosis: timing and pathway relationships.

During meiosis, crossovers occur at a high level, but the level of noncrossover recombinants is even higher. The biological rationale for the existence of the latter events is not known. It has been suggested that a noncrossover-specific pathway exists specifically to mediate chromosome pairing. Using a physical assay that monitors both crossovers and noncrossovers in cultures of yeast undergoing synchronous meiosis, we find that both types of products appear at essentially the same time, after chromosomes are fully synapsed at pachytene. We have also analyzed a situation in which commitment to meiotic recombination and formation of the synaptonemal complex are coordinately suppressed (mer1 versus mer1 MER2++). We find that suppression is due primarily to restoration of meiosis-specific double-strand breaks, a characteristic of the major meiotic recombination pathway. Taken together, the observations presented suggest that there probably is no noncrossover-specific pathway and that restoration of intermediate events in a single pairing/recombination pathway promotes synaptonemal complex formation. The biological significant of noncrossover recombination remains to be determined, however.

Differentiation between homoeologous chromosomes 1A of wheat and 1Am of Triticum monococcum and its recognition by the wheat Ph1 locus.

In most allopolyploid plants, only homogenetic chromosome pairing occurs in meiosis, as a result of the recognition of genome differentiation by the genetic system regulating meiotic chromosome pairing. The nature of differentiation between chromosomes of closely related genomes is examined here by investigating recombination between wheat chromosome 1A and the closely related homoeologous chromosome 1Am of Triticum monococcum. The recognition of the differentiation between these chromosomes by the Ph1 locus, which prevents heterogenetic chromosome pairing in wheat, is also investigated. Chromosomes 1A and 1Am are shown to be colinear, and it is concluded that they are differentiated "substructurally." This substructural differentiation is argued to be recognized by the Ph1 locus. In the absence of Ph1, the distribution and frequencies of crossing over between the 1A and 1Am homoeologues were similar to the distribution and frequencies of crossing over between 1A homologues. The cytogenetic and evolutionary significance of these findings is discussed.

The Ste locus, a component of the parasitic cry-Ste system of Drosophila melanogaster, encodes a protein that forms crystals in primary spermatocytes and mimics properties of the beta subunit of casein kinase 2.

Males of Drosophila melanogaster lacking the Y chromosome-linked crystal locus show multiple meiotic alterations including chromosome disorganization and prominent crystal formation in primary spermatocytes. These alterations are due to the derepression of the X chromosome-linked Stellate sequences. To understand how the derepression of the Stellate elements gives rise to these abnormalities, we have expressed the protein encoded by the Stellate sequences in bacteria and produced an antibody against the fusion protein. Immunostaining of crystal- testes has clearly shown that the Stellate protein is a major component of the crystals. Moreover, in vitro experiments have shown that this protein can interact with the catalytic alpha subunit of casein kinase 2 enzyme, altering its activity.

Efetividade dos instrumentos de políticas públicas nos gastos privados de P&D no Brasil

Esse trabalho teve como objetivo contribuir para o debate sobre a importância das políticas de incentivo à inovação no Brasil. Os resultados esperados do uso que as empresas fizeram dos diferentes tipos de instrumentos sobre os gastos em pesquisa e desenvolvimento (P&D) foram avaliados pelo método de diferenças em diferenças. O método permitiu obter as diferenças de gastos entre empresas beneficiárias de instrumentos e as não-beneficiárias em três períodos consecutivos: 2005 em relação à 2003; 2008 em relação à 2005 e de 2011 em relação à 2008. Ao fazer isso, foi possível identificar se tais diferenças foram positivas e significativas, podendo ser atribuídas às influências dos instrumentos. Os instrumentos utilizados foram: incentivos fiscais, Lei de Informática, financiamentos em parcerias, financiamentos sem parcerias e subvenção. E a utilização dos mesmos pelas empresas teve maior relevância no âmbito de diversos programas de apoio à inovação vigentes no país a partir da retomada das políticas industriais e tecnológicas, nos anos 2000. O estudo concluiu que os efeitos positivos e significativos são limitados à determinados grupos tecnológicos e à poucos instrumentos, em geral, de caráter fiscal. Além disso, esses efeitos positivos surgem em apenas um período, sendo que para cada grupo tecnológico foram efetuadas estimativas para três períodos. Também não houve evidências de que os instrumentos financeiros exerçam efeitos significativos sobre as decisões de gastos em pesquisa e desenvolvimento, apesar da maior ênfase dada aos mesmos no período estudado. Os resultados sugerem fraca influência dos mecanismos de apoio à P&D no Brasil sobre o aumento dos gastos privados, apesar dos avanços recentes.

A Proper Yield Curve for Greece to Kick-Start Financial Intermediation. ECMI Policy Brief No. 21, 10 December 2013

At present, the market is severely mispricing Greece’s sovereign risk relative to the country’s fundamentals. As a result of the mispricing, financial intermediation in Greece has become dysfunctional and the privatisation of state-owned assets has stalled. This mispricing is partially due to an illiquid and fragmented government yield curve. A well-designed public liability management exercise can lead to a more efficient pricing of Greece’s government bonds and thereby help restore stable and affordable financing for the country’s private sector, which is imperative in order to overcome Greece’s deep recession. This paper proposes three measures to enhance the functioning of the Greek government debt market: i) Greece should issue a new five-year bond, ii) it should consolidate the 20 individual series of government bonds into four liquid securities and iii) it should offer investors a swap of these newly created bonds into dollar-denominated securities. Each of these measures would be beneficial to the Hellenic Republic, since the government would be able to reduce the face value and the net present value of its debt stock. Furthermore, this exercise would facilitate the resumption of market access, which is a necessary condition for continuous multilateral disbursements to Greece.

The fragile ‘reset’. The balance sheet and the prospects for changes in Russian-US relations. OSW Point of View (Policy Brief), April 2011

The ‘reset’ policy proposed by the USA has brought Russia a number of geopolitical, prestigious and economic benefits. The most important of those are: the resumption of arms control, the USA’s withdrawal from plans to locate elements of its strategic missile defence system in Poland and the Czech Republic, and the entry into force of the so-called 123 Agreement. In response, Russia has assisted the United States in resolving the Iranian crisis, and offered help with the Afghanistan operation, covering the transit of supplies and supporting the Afghan government. Moscow has also eased up on its anti-American rhetoric. The changes which have taken place in Russian-US relations are not durable. The two parties have not resolved their major disputes (for example, regarding missile defence), and any differences are hushed up for tactical reasons.

Nagorno-Karabkh - conflict unfreezing. OSW Commentary No. 65, 2011-10-26

The conflict between Armenia and Azerbaijan over Nagorno-Karabakh poses the greatest challenge to the security and stability of the Southern Caucasus. Although a ceasefire has been in place and a peace process under way since 1994, there is growing concern that the threat of the resumption of military action is growing. Proof of that is provided by, for example, the arms race dictated by Azerbaijan and its use of war rhetoric. A major factor, in addition to Azerbaijan’s increasing potential and ambitions, which is destabilising the situation concerning Karabakh seems to be the changing geopolitical situation in this region. Although the outbreak of a new war over Nagorno-Karabakh seems unlikely (as this would be risky to all the actors involved) within the next year, if the current trends continue, this will be difficult to avoid in the future. A further increase in the tension, and especially a military conflict (whatever its outcome), will lead to deep changes in the situation in the Southern Caucasus and in the policies of the countries which are active in this region.

An inexhaustible source of income? The significance of Belarusian refineries and the outlook for the future. OSW Commentary No. 81, 2012-06-20

Belarus generated a surplus at US$1.9 billion in foreign trade in goods and services in the first four months of 2012 as compared to a deficit of US$2.8 billion for the same timeframe a year earlier. Minsk owes this, its highest positive trade balance since 1991, mainly to a significant increase in exports of petroleum products manufactured by the refineries in Navapolatsk and Mazyr. This is a consequence of the favourable contract for supplies of Russian oil until 2015 which Belarus signed in December last year. This contract has resulted in a de facto resumption of Russia subsidising Belarus. The favourable conditions of Russian oil supplies will allow the Belarusian refineries to remain the driving force of the country’s economy, and the Belarusian government will not allow them to be privatised, which Russia has been seeking for years. The two refineries initiated an ambitious modernisation programme, which is aimed at increasing their output and improving the quality of their production. Owing to this, their share in the market of petroleum products in the region, including on the Polish market, may grow within the next few years.

Distinct mechanisms eliminate mother and daughter centrioles in meiosis of starfish oocytes

Centriole elimination is an essential process that occurs in female meiosis of metazoa to reset centriole number in the zygote at fertilization. How centrioles are eliminated remains poorly understood. Here we visualize the entire elimination process live in starfish oocytes. Using specific fluorescent markers, we demonstrate that the two older, mother centrioles are selectively removed from the oocyte by extrusion into polar bodies. We show that this requires specific positioning of the second meiotic spindle, achieved by dynein-driven transport, and anchorage of the mother centriole to the plasma membrane via mother-specific appendages. In contrast, the single daughter centriole remaining in the egg is eliminated before the first embryonic cleavage. We demonstrate that these distinct elimination mechanisms are necessary because if mother centrioles are artificially retained, they cannot be inactivated, resulting in multipolar zygotic spindles. Thus, our findings reveal a dual mechanism to eliminate centrioles: mothers are physically removed, whereas daughters are eliminated in the cytoplasm, preparing the egg for fertilization.

Patterns of Stem Cell Divisions Contribute to Plant Longevity

The lifespan of plants ranges from a few weeks in annuals to thousands of years in trees. It is hard to explain such extreme longevity considering that DNA replication errors inevitably cause mutations. Without purging through meiotic recombination, the accumulation of somatic mutations will eventually result in mutational meltdown, a phenomenon known as Muller’s ratchet. Nevertheless, the lifespan of trees is limited more often by incidental disease or structural damage than by genetic aging. The key determinants of tree architecture are the axillary meristems, which form in the axils of leaves and grow out to form branches. The number of branches is low in annual plants, but in perennial plants iterative branching can result in thousands of terminal branches. Here, we use stem cell ablation and quantitative cell-lineage analysis to show that axillary meristems are set aside early, analogous to the metazoan germline. While neighboring cells divide vigorously, axillary meristem precursors maintain a quiescent state, with only 7–9 cell divisions occurring between the apical and axillary meristem. During iterative branching, the number of branches increases exponentially, while the number of cell divisions increases linearly. Moreover, computational modeling shows that stem cell arrangement and positioning of axillary meristems distribute somatic mutations around the main shoot, preventing their fixation and maximizing genetic heterogeneity. These features slow down Muller’s ratchet and thereby extend lifespan.

Miscellaneous works.

1. The harmony of interest. Letters on international copyright, ed. 2. Money. Letters to the President, on the foreign and domestic policy of the union. Financial crises: their causes and effects. --2. Letters to Schuyler Colfax on the paper, the iron, the farmer's, the railroad and the currency questions. The public debt, local and national. Contraction or expansion? Repudiation or resumption? British free trade. Review of the decade 1857-67. Reconstruction: industrial, financial and political. The finance minister, the currency, and the public debt. Shall we have peace?: Letters to the President elect of the U.S. Review of the report of D. A. Wells. Resumption. Review of the farmer's question. Wealth: of what does it consist? International copyright question considered. Memoir of Stephen Colwell.

Publications of the United States Naval Observatory.

Mode of access: Internet.