Structural and functional insight into TAF1-TAF7, a subcomplex of transcription factor II D.

Transcription factor II D (TFIID) is a multiprotein complex that nucleates formation of the basal transcription machinery. TATA binding protein-associated factors 1 and 7 (TAF1 and TAF7), two subunits of TFIID, are integral to the regulation of eukaryotic transcription initiation and play key roles in preinitiation complex (PIC) assembly. Current models suggest that TAF7 acts as a dissociable inhibitor of TAF1 histone acetyltransferase activity and that this event ensures appropriate assembly of the RNA polymerase II-mediated PIC before transcriptional initiation.

Leishmaniasis in an era of conflict in the Middle East.

Leishmaniasis is endemic in the Middle East, and both cutaneous and visceral forms are reported from the region ranging from the Levant to Afghanistan. The potential and proven phlebotomine sand fly vectors and reservoir hosts of the Leishmaniases species in Afghanistan, Iran, Iraq, Israel, Jordan, Lebanon, Saudi Arabia, Syria, Turkey, and Yemen are described. This region has seen a movement of populations across the area, due to both military and civilian strife.

The development of artemisinin resistance in malaria: reasons and solutions.

Despite world-wide efforts in fighting malaria, this mosquito-borne infectious disease is a huge burden for the population, especially in tropical and subtropical areas. The WHO recommends artemisinin-based combination therapy for the treatment of uncomplicated Plasmodium falciparum malaria. However, artemisinin resistance cannot now be ignored.

Crystal structure of the three tandem FF domains of the transcription elongation regulator CA150.

FF domains are small protein-protein interaction modules that have two flanking conserved phenylalanine residues. They are present in proteins involved in transcription, RNA splicing, and signal transduction, and often exist in tandem arrays. Although several individual FF domain structures have been determined by NMR, the tandem nature of most FF domains has not been revealed.

Characterization of transcription from TATA-less promoters: identification of a new core promoter element XCPE2 and analysis of factor requirements.

Background: More than 80% of mammalian protein-coding genes are driven by TATA-less promoters which often show multiple transcriptional start sites (TSSs). However, little is known about the core promoter DNA sequences or mechanisms of transcriptional initiation for this class of promoters.

Methodology/principal Findings: Here we identify a new core promoter element XCPE2 (X core promoter element 2) (consensus sequence: A/C/G-C-C/T-C-G/A-T-T-G/A-C-C/A(+1)-C/T) that can direct specific transcription from the second TSS of hepatitis B virus X gene mRNA.

Glycolytic and chitinolytic activities of Phlebotomus papatasi (Diptera: Psychodidae) from diverse ecological habitats.

The sand fly Phlebotomus papatasi Scopoli, 1786, the vector of Leishmania major Yakimoff et Schokhor, 1914, is found in desert areas where sugars are scarce but also in habitats that abound in sugar sources. The sand flies require sugar meals from plant sources for their energy requirements and to hydrolyze these complex sugars, they need a repertoire of glycosidases. We presumed that there are differences in the levels of glycosidase activities in flies from such habitats and also assumed that they may be instrumental in modulating the flies' susceptibility to L.

Gliotoxin production in Aspergillus fumigatus contributes to host-specific differences in virulence.

Background: Gliotoxin is a epipolythiodioxopiperazine toxin that is made by the filamentous fungus Aspergillus fumigatus. Gliotoxin has a wide range of effects on metazoan cells in culture, including induction of apoptosis through inhibition of Nf-kappaB, and inhibition of superoxide production by phagocytes. These activities have led to the proposal that gliotoxin contributes to pathogenesis during invasive aspergillosis.

Dynamic interplay between nitration and phosphorylation of tubulin cofactor B in the control of microtubule dynamics.

Tubulin cofactor B (TCoB) plays an important role in microtubule dynamics by facilitating the dimerization of alpha- and beta-tubulin. Recent evidence suggests that p21-activated kinase 1 (Pak1), a major signaling nodule in eukaryotic cells, phosphorylates TCoB on Ser-65 and Ser-128 and plays an essential role in microtubule regrowth. However, to date, no upstream signaling molecules have been identified to antagonize the functions of TCoB, which might help in maintaining the equilibrium of microtubules.

Crystallographic and biochemical analysis of rotavirus NSP2 with nucleotides reveals a nucleoside diphosphate kinase-like activity.

Rotavirus, the major pathogen of infantile gastroenteritis, carries a nonstructural protein, NSP2, essential for viroplasm formation and genome replication/packaging. In addition to RNA-binding and helix-destabilizing properties, NSP2 exhibits nucleoside triphosphatase activity. A conserved histidine (H225) functions as the catalytic residue for this enzymatic activity, and mutation of this residue abrogates genomic double-stranded RNA synthesis without affecting viroplasm formation.

Conserved region I of human coactivator TAF4 binds to a short hydrophobic motif present in transcriptional regulators.

TBP-associated factor 4 (TAF4), an essential subunit of the TFIID complex acts as a coactivator for multiple transcriptional regulators, including Sp1 and CREB. However, little is known regarding the structural properties of the TAF4 subunit that lead to the coactivator function. Here, we report the crystal structure at 2.

The new core promoter element XCPE1 (X Core Promoter Element 1) directs activator-, mediator-, and TATA-binding protein-dependent but TFIID-independent RNA polymerase II transcription from TATA-less promoters.

The core promoter is a critical DNA element required for accurate transcription and regulation of transcription. Several core promoter elements have been previously identified in eukaryotes, but those cannot account for transcription from most RNA polymerase II-transcribed genes. Additional, as-yet-unidentified core promoter elements must be present in eukaryotic genomes.

Genetic and biological diversity among populations of Leishmania major from Central Asia, the Middle East and Africa.

Evidence is provided for genetic and biological variation among Leishmania major strains that correlates with their geographical origin. The host-parasite relationship also appears to be specific. Great gerbils, Rhombomys opimus, and fat sand rats, Psammomys obesus, are the main reservoir hosts in Central Asia and the Middle East, respectively.

Multifarious characterization of leishmania tropica from a Judean desert focus, exposing intraspecific diversity and incriminating phlebotomus sergenti as its vector.

The predominant sand fly species collected inside houses in Kfar Adumim, an Israeli village in the Judean Desert that is a focus of cutaneous leishmaniasis, was Phlebotomus papatasi, which was also caught attempting to bite humans. Phlebotomus sergenti, which is rarely seen inside houses, constituted the predominant sand fly species in caves near the village. Leishmania isolates from Ph.

Leishmania tropica (Kinetoplastida: Trypanosomatidae)--a perplexing parasite.

Leishmania tropica is one of the causative agents of cutaneous leishmaniasis (CL), a disfiguring parasitic disease that recently was found to be viscerotropic. In urban areas it is transmitted from infected individuals by the bite of phlebotomine sand flies to naïve persons (anthroponotic CL). In rural areas animals are thought to be the reservoir, but the full life cycle is still under investigation (zoonotic CL).

Outbreak of cutaneous leishmaniasis in northern Israel.

This study describes a new focus of cutaneous leishmaniasis (CL) due to Leishmania tropica, in the Galilee region of northern Israel. Thirty-three cases from 4 villages (northern part) and from the city of Tiberias (southern part) have been clinically diagnosed since 1996. Parasites from 13 patients and from 6 sand flies were characterized by isoenzyme electrophoresis, 2 immunological methods, and 3 polymerase chain reaction (PCR)-based methods.

Functional inactivation of a transcriptional corepressor by a signaling kinase.

The C-terminal binding protein 1 (CtBP) is a ubiquitous corepressor linking the recruitment of DNA- and histone-modifying proteins to sequence-specific DNA-binding proteins and facilitating gene regulation during development and oncogenesis. We describe here the binding, phosphorylation and functional regulation of CtBP by the p21-activated kinase 1 (Pak1). Pak1 phosphorylates CtBP selectively on Ser158 within a putative regulatory loop, triggering CtBP cellular redistribution and blocking CtBP corepressor functions.