Strand specificity in the transcriptional targeting of recombination at immunoglobulin switch sequences.

B-lymphocyte-specific class switch recombination is known to occur between pairs of 2- to 10-kb switch regions located immediately upstream of the immunoglobulin constant heavy-chain genes. Others have shown that the recombination is temporally correlated with the induction of transcription at the targeted switch regions. To determine whether this temporal correlation is due to a mechanistic linkage, we have developed an extrachromosomal recombination assay that closely recapitulates DNA deletional class switch recombination. In this assay, the rate of recombination is measured between 24 and 48 hr posttransfection. We find that recombinants are generated in a switch sequence-dependent manner. Recombination occurs with a predominance within B-cell lines representative of the mature B-cell stage and within a subset of pre-B-cell lines. Transcription stimulates the switch sequence-dependent recombination. Importantly, transcription activates recombination only when directed in the physiologic orientation but has no effect when directed in the nonphysiologic orientation.

Differential subcellular mRNA targeting: deletion of a single nucleotide prevents the transport to axons but not to dendrites of rat hypothalamic magnocellular neurons.

It has previously been shown that mRNA encoding the arginine vasopressin (AVP) precursor is targeted to axons of rat magnocellular neurons of the hypothalamo-neurohypophyseal tract. In the homozygous Brattle-boro rat, which has a G nucleotide deletion in the coding region of the AVP gene, no such targeting is observed although the gene is transcribed. RNase protection and heteroduplex analyses demonstrate that, in heterozygous animals, which express both alleles of the AVP gene, the wild-type but not the mutant transcript is subject to axonal compartmentation. In contrast, wild-type and mutant AVP mRNAs are present in dendrites. These data suggest the existence of different mechanisms for mRNA targeting to the two subcellular compartments. Axonal mRNA localization appears to take place after protein synthesis; the mutant transcript is not available for axonal targeting because it lacks a stop codon preventing its release from ribosomes. Dendritic compartmentation, on the other hand, is likely to precede translation and, thus, would be unable to discriminate between the two mRNAs.

Inflation-Targeting, Flexible Exchange Rates and Macroeconomic Performance since the Great Recession. CEPS Working Document No. 394, March 2014

Has inflation targeting (IT) conferred benefits in terms of economic growth on countries that followed this particular monetary policy strategy during the crisis period 2007-12? This paper answers this question in the affirmative. Countries with an IT monetary regime with flexible exchange rates weathered the crisis much better than countries with other monetary regimes, predominantly countries with fixed exchange rates. Part of this difference in growth performance reflects differences in export performance during the initial years of the crisis, which in turn can be explained by real exchange rate depreciations. However, IT seems also to confer other benefits on the countries above and beyond the effects from currency depreciation.

Assessing US and EU Foreign Targeting Arab Youth: Lessons from Morocco. ACES Working Papers (progress report), August 2009

As stated in the opening sentence of the proposal submitted for the ACES grant in 2009, the research that this seed grant is supporting is ambitious and large in scale. The primary goal is to produce a book-length study that assesses the priorities and impact of European and American foreign aid targeting youth in the Middle East and North Africa (MENA). To date, the research undertaken with the support of the grant has helped in providing some preliminary data for a) testing few hypotheses, b) fine-tuning the research design; and c) pointing to the direction where more conceptual and ethnographic research should be undertaken.

Epigenetic engineering shows H3K4me2 is required for HJURP targeting and CENP-A assembly on a synthetic human kinetochore

Kinetochores assemble on distinct 'centrochromatin' containing the histone H3 variant CENP-A and interspersed nucleosomes dimethylated on H3K4 (H3K4me2). Little is known about how the chromatin environment at active centromeres governs centromeric structure and function. Here, we report that centrochromatin resembles K4-K36 domains found in the body of some actively transcribed housekeeping genes. By tethering the lysine-specific demethylase 1 (LSD1), we specifically depleted H3K4me2, a modification thought to have a role in transcriptional memory, from the kinetochore of a synthetic human artificial chromosome (HAC). H3K4me2 depletion caused kinetochores to suffer a rapid loss of transcription of the underlying α-satellite DNA and to no longer efficiently recruit HJURP, the CENP-A chaperone. Kinetochores depleted of H3K4me2 remained functional in the short term, but were defective in incorporation of CENP-A, and were gradually inactivated. Our data provide a functional link between the centromeric chromatin, α-satellite transcription, maintenance of CENP-A levels and kinetochore stability.

GFP-targeting allows visualization of the apicoplast throughout the life cycle of live malaria parasites.

BACKGROUND INFORMATION The Plasmodium parasite, during its life cycle, undergoes three phases of asexual reproduction, these being repeated rounds of erythrocytic schizogony, sporogony within oocysts on the mosquito midgut wall and exo-erythrocytic schizogony within the hepatocyte. During each phase of asexual reproduction, the parasite must ensure that every new daughter cell contains an apicoplast, as this organelle cannot be formed de novo and is essential for parasite survival. To date, studies visualizing the apicoplast in live Plasmodium parasites have been restricted to the blood stages of Plasmodium falciparum. RESULTS In the present study, we have generated Plasmodium berghei parasites in which GFP (green fluorescent protein) is targeted to the apicoplast using the specific targeting sequence of ACP (acyl carrier protein), which has allowed us to visualize this organelle in live Plasmodium parasites. During each phase of asexual reproduction, the apicoplast becomes highly branched, but remains as a single organelle until the completion of nuclear division, whereupon it divides and is rapidly segregated into newly forming daughter cells. We have shown that the antimicrobial agents azithromycin, clindamycin and doxycycline block development of the apicoplast during exo-erythrocytic schizogony in vitro, leading to impaired parasite maturation. CONCLUSIONS Using a range of powerful live microscopy techniques, we show for the first time the development of a Plasmodium organelle through the entire life cycle of the parasite. Evidence is provided that interference with the development of the Plasmodium apicoplast results in the failure to produce red-blood-cell-infective merozoites.

Differences Between Monetary and Multidimensional Poverty in the Lao PDR: Implications for Targeting of Poverty Reduction Policies and Interventions

This study compares monetary and multidimensional poverty measures for the Lao People’s Democratic Republic. Using household data of 2007/2008, we compare the empirical outcomes of the country’s current official monetary poverty measure with those of a multidimensional poverty measure. We analyze which population subgroups are identified as poor by both measures and thus belong to the category of the poorest of the poor; and we look at which subgroups are identified as poor by only one of the measures and belong either to the category of the income-poor (identified as poor only by the monetary measure) or to that of the overlooked poor (identified as poor only by the multidimensional poverty measure). Furthermore, we examined drivers of these differences using a multinomial regression model and found that monetary poverty does not capture the multiple deprivations of ethnic minorities, who are only identified as poor when using a multidimensional poverty measure. We conclude that complementing the monetary poverty measure with a multidimensional poverty index would enable more effective targeting of poverty reduction efforts.

Better targeting of federal funds needed to eliminate unsafe bridges. Comptroller General's report to the Honorable James R. Sasser, United States Senate.

Mode of access: Internet.

Saturation patrols targeting impaired driving - guidelines for community-based alcohol enforcement programs.

Mode of access: Internet.

Use by the Department of the Treasury of the geographic targeting order as a method to combat money laundering : hearing before the Subcommittee on General Oversight and Investigations of the Committee on Banking and Financial Services, House of Representatives, One Hundred Fifth Congress, first session, March 11, 1997.

"Serial no. 105-7."

Saturation patrols targeting imparied driving : guidelines for community-based alcohol enforcement programs.

"DOT HS 807 983"--P. [4] of cover.

An Assessment of local government management motivational programs : performance targeting with and without monetary incentives /

"September 30, 1981."

Farm payments : implications of targeting farm income supports : report to the Honorable Jesse Helms, U.S. Senate /

"GAO/RECD-87-99"-- cover.