1,768 research outputs found
A land of milk and honey with streets paved with gold: do emigrants have over-optimistic expectations about incomes abroad?
Millions of people emigrate every year in search of better economic and social
opportunities. Anecdotal evidence suggests that emigrants may have over-optimistic
expectations about the incomes they can earn abroad, resulting in excessive
migration pressure, and in disappointment amongst those who do migrate. Yet there
is almost no statistical evidence on how accurately these emigrants predict the
incomes that they will earn working abroad. In this paper we combine a natural
emigration experiment with unique survey data on would-be emigrants’ probabilistic
expectations about employment and incomes in the migration destination. Our
procedure enables us to obtain moments and quantiles of the subjective distribution
of expected earnings in the destination country. We find a significant underestimation
of both unconditional and conditional labor earnings at all points in the
distribution. This under-estimation appears driven in part by potential migrants
placing too much weight on the negative employment experiences of some
migrants, and by inaccurate information flows from extended family, who may be
trying to moderate remittance demands by understating incomes
Replication factor-A from Saccharomyces cerevisiae is encoded by three essential genes coordinately expressed at S phase
Replication factor-A (RF-A) is a three-subunit protein complex originally purified from human cells as an essential component for SV40 DNA replication in vitro. We have previously identified a functionally homologous three-subunit protein complex from the yeast Saccharomyces cerevisiae. Here we report the cloning and characterization of the genes encoding RF-A from S. cerevisiae. Each of the three subunits is encoded by a single essential gene. Cells carrying null mutations in any of the three genes arrest as budded and multiply budded cells. All three genes are expressed in a cell-cycle-dependent manner; the mRNA for each subunit peaks at the G1/S-phase boundary. A comparison of protein sequences indicates that the human p34 subunit is 29% identical to the corresponding RFA2 gene product. However, expression of the human protein fails to rescue the rfa2::TRP1 disruption
The Porcelain Crab Transcriptome and PCAD, the Porcelain Crab Microarray and Sequence Database
BACKGROUND: With the emergence of a completed genome sequence of the freshwater crustacean Daphnia pulex, construction of genomic-scale sequence databases for additional crustacean sequences are important for comparative genomics and annotation. Porcelain crabs, genus Petrolisthes, have been powerful crustacean models for environmental and evolutionary physiology with respect to thermal adaptation and understanding responses of marine organisms to climate change. Here, we present a large-scale EST sequencing and cDNA microarray database project for the porcelain crab Petrolisthes cinctipes. METHODOLOGY/PRINCIPAL FINDINGS: A set of approximately 30K unique sequences (UniSeqs) representing approximately 19K clusters were generated from approximately 98K high quality ESTs from a set of tissue specific non-normalized and mixed-tissue normalized cDNA libraries from the porcelain crab Petrolisthes cinctipes. Homology for each UniSeq was assessed using BLAST, InterProScan, GO and KEGG database searches. Approximately 66% of the UniSeqs had homology in at least one of the databases. All EST and UniSeq sequences along with annotation results and coordinated cDNA microarray datasets have been made publicly accessible at the Porcelain Crab Array Database (PCAD), a feature-enriched version of the Stanford and Longhorn Array Databases. CONCLUSIONS/SIGNIFICANCE: The EST project presented here represents the third largest sequencing effort for any crustacean, and the largest effort for any crab species. Our assembly and clustering results suggest that our porcelain crab EST data set is equally diverse to the much larger EST set generated in the Daphnia pulex genome sequencing project, and thus will be an important resource to the Daphnia research community. Our homology results support the pancrustacea hypothesis and suggest that Malacostraca may be ancestral to Branchiopoda and Hexapoda. Our results also suggest that our cDNA microarrays cover as much of the transcriptome as can reasonably be captured in EST library sequencing approaches, and thus represent a rich resource for studies of environmental genomics
Terahertz Response of Field-Effect Transistors in Saturation Regime
We report on the broadband THz response of InGaAs/GaAs HEMTs operating at
1.63 THz and room temperature deep in the saturation regime. We demonstrate
that responses show linear increase with drain-to-source voltage (or drain bias
current) and reach very high values up to 170V/W. We also develop a
phenomenological theory valid both in the ohmic and in the saturation regimes.Comment: 11 pages, 3 figure
The origin recognition complex in silencing, cell cycle progression, and DNA replication
This report describes the isolation of ORC5, the gene encoding the fifth largest subunit of the origin recognition complex, and the properties of mutants with a defective allele of ORC5. The orc5-1 mutation caused temperature-sensitive growth and, at the restrictive temperature, caused cell cycle arrest. At the permissive temperature, the orc5-1 mutation caused an elevated plasmid loss rate that could be suppressed by additional tandem origins of DNA replication. The sequence of ORC5 revealed a potential ATP binding site, making Orc5p a candidate for a subunit that mediates the ATP-dependent binding of ORC to origins. Genetic interactions among orc2-1 and orc5-1 and other cell cycle genes provided further evidence for a role for the origin recognition complex (ORC) in DNA replication. The silencing defect caused by orc5-1 strengthened previous connections between ORC and silencing, and combined with the phenotypes caused by orc2 mutations, suggested that the complex itself functions in both processes
Inhibition of CDK activity and PCNA-dependent DNA replication by p21 is blocked by interaction with the HPV-16 E7Â oncoprotein
p21 inhibits cyclin-dependent kinase (CDK) activity and proliferating cell nuclear antigen (PCNA)-dependent DNA replication by binding to CDK/cyclin complexes and to PCNA through distinct domains. The human papillomavirus (HPV)-16 E7 oncoprotein (16E7) abrogated a DNA damage-induced cell cycle arrest in vivo, despite high levels of p21. Using cell lysates and purified proteins we show that 16E7 prevented p21 both from inhibiting CDK2/cyclin E activity and PCNA-dependent DNA replication, whereas the nononcogenic HPV-6 E7 had reduced effects. Inactivation of both inhibitory functions of p21 was attained through binding between 16E7 and sequences in the carboxy-terminal end of p21 that overlap with the PCNA-binding site and the second p21 cyclin-binding motif. These data imply that the carboxyl terminus of p21 simultaneously modulates both CDK activity and PCNA-dependent DNA replication and that a single protein, 16E7, can override this modulation to disrupt normal cell cycle control
Epigenetic Chromatin Silencing: Bistability and Front Propagation
The role of post-translational modification of histones in eukaryotic gene
regulation is well recognized. Epigenetic silencing of genes via heritable
chromatin modifications plays a major role in cell fate specification in higher
organisms. We formulate a coarse-grained model of chromatin silencing in yeast
and study the conditions under which the system becomes bistable, allowing for
different epigenetic states. We also study the dynamics of the boundary between
the two locally stable states of chromatin: silenced and unsilenced. The model
could be of use in guiding the discussion on chromatin silencing in general. In
the context of silencing in budding yeast, it helps us understand the phenotype
of various mutants, some of which may be non-trivial to see without the help of
a mathematical model. One such example is a mutation that reduces the rate of
background acetylation of particular histone side-chains that competes with the
deacetylation by Sir2p. The resulting negative feedback due to a Sir protein
depletion effect gives rise to interesting counter-intuitive consequences. Our
mathematical analysis brings forth the different dynamical behaviors possible
within the same molecular model and guides the formulation of more refined
hypotheses that could be addressed experimentally.Comment: 19 pages, 5 figure
Reversible suppression of an essential gene in adult mice using transgenic RNA interference
RNAi has revolutionized loss-of-function genetics by enabling sequence-specific suppression of virtually any gene. Furthermore, tetracycline response elements (TRE) can drive expression of short hairpin RNAs (shRNAs) for inducible and reversible target gene suppression. Here, we demonstrate the feasibility of transgenic inducible RNAi for suppression of essential genes. We set out to directly target cell proliferation by screening an RNAi library against DNA replication factors and identified multiple shRNAs against Replication Protein A, subunit 3 (RPA3). We generated transgenic mice with TRE-driven Rpa3 shRNAs whose expression enforced a reversible cell cycle arrest. In adult mice, the block in cell proliferation caused rapid atrophy of the intestinal epithelium which led to weight loss and lethality within 8-11 d of shRNA induction. Upon shRNA withdrawal, villus atrophy and weight loss were fully reversible. Thus, shRpa3 transgenic mice provide an interesting tool to study tissue maintenance and regeneration. Overall, we have established a robust system that serves the purpose of temperature-sensitive alleles in other model organisms, enabling inducible and reversible suppression of essential genes in a mammalian system
Structural and mechanistic insights into Mcm2-7 double-hexamer assembly and function
Eukaryotic cells license each DNA replication origin during G1 phase by assembling a prereplication complex that contains a Mcm2-7 (minichromosome maintenance proteins 2-7) double hexamer. During S phase, each Mcm2-7 hexamer forms the core of a replicative DNA helicase. However, the mechanisms of origin licensing and helicase activation are poorly understood. The helicase loaders ORC-Cdc6 function to recruit a single Cdt1-Mcm2-7 heptamer to replication origins prior to Cdt1 release and ORC-Cdc6-Mcm2-7 complex formation, but how the second Mcm2-7 hexamer is recruited to promote double-hexamer formation is not well understood. Here, structural evidence for intermediates consisting of an ORC-Cdc6-Mcm2-7 complex and an ORC-Cdc6-Mcm2-7-Mcm2-7 complex are reported, which together provide new insights into DNA licensing. Detailed structural analysis of the loaded Mcm2-7 double-hexamer complex demonstrates that the two hexamers are interlocked and misaligned along the DNA axis and lack ATP hydrolysis activity that is essential for DNA helicase activity. Moreover, we show that the head-to-head juxtaposition of the Mcm2-7 double hexamer generates a new protein interaction surface that creates a multisubunit-binding site for an S-phase protein kinase that is known to activate DNA replication. The data suggest how the double hexamer is assembled and how helicase activity is regulated during DNA licensing, with implications for cell cycle control of DNA replication and genome stability
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