The Epstein-Barr Virus Episome Maneuvers between Nuclear Chromatin Compartments during Reactivation.

The human genome is structurally organized in three-dimensional space to facilitate functional partitioning of transcription. We learned that the latent episome of the human Epstein-Barr virus (EBV) preferentially associates with gene-poor chromosomes and avoids gene-rich chromosomes. Kaposi's sarcoma-associated herpesvirus behaves similarly, but human papillomavirus does not. Contacts on the EBV side localize to OriP, the latent origin of replication. This genetic element and the EBNA1 protein that binds there are sufficient to reconstitute chromosome association preferences of the entire episome. Contacts on the human side localize to gene-poor and AT-rich regions of chromatin distant from transcription start sites. Upon reactivation from latency, however, the episome moves away from repressive heterochromatin and toward active euchromatin. Our work adds three-dimensional relocalization to the molecular events that occur during reactivation. Involvement of myriad interchromosomal associations also suggests a role for this type of long-range association in gene regulation.IMPORTANCE The human genome is structurally organized in three-dimensional space, and this structure functionally affects transcriptional activity. We set out to investigate whether a double-stranded DNA virus, Epstein-Barr virus (EBV), uses mechanisms similar to those of the human genome to regulate transcription. We found that the EBV genome associates with repressive compartments of the nucleus during latency and with active compartments during reactivation. This study advances our knowledge of the EBV life cycle, adding three-dimensional relocalization as a novel component to the molecular events that occur during reactivation. Furthermore, the data add to our understanding of nuclear compartments, showing that disperse interchromosomal interactions may be important for regulating transcription

Identification of Reissner's fiber-like glycoproteins in two species of freshwater planarians (Tricladida), by use of specific polyclonal and monoclonal antibodies

By using one polyclonal antiserum raised against bovine Reissner's fiber and seven monoclonal antibodies raised against bovine Reissner's fiber and against immunopurified bovine subcommissural organ glycoproteins, we have investigated two freshwater planarian species (Girardia tigrina, Schmidtea mediterranea) by light- and electron-microscopic immunocytochemistry. ELISA probes showed that the monoclonal antibodies recognized different, nonoverlapping, unrepeated, proteinaceous epitopes present in the same compounds of bovine Reissner's fiber. Cells immunoreactive to the polyclonal and monoclonal antibodies were found in the dorsal and ventral integument of both planarian species. Labeled cuboid epidermal cells bore cilia and displayed several types of secretory granules; they were covered by a film of immunoreactive material. Studies on adjacent thin and semithin sections revealed coexistence of label in the same regions and in the same cells when two different monoclonal antibodies were used. These results indicate that a secretory substance immunologically similar to the secretion of the vertebrate subcommissural organ is present in primitive tripoblasts such as planarians, suggesting that these secretions are ancient and well conserved in phylogeny

Gravitino perturbations in Schwarzschild black holes

We consider the time evolution of massless gravitino perturbations in Schwarzschild black holes, and show that as in the case of fields of other values of spin, the evolution comes in three stages, after an initial outburst as a first stage, we observe the damped oscillations characteristic of the quasinormal ringing stage, followed by long time tails. Using the sixth order WKB method and Prony fitting of time domain data we determine the quasinormal frequencies. There is a good correspondence between the results obtained by the above two methods, and we obtain a considerable improvement with respect to the previously obtained third order WKB results. We also show that the response of a black hole depends crucially on the spin class of the perturbing field: the quality factor becomes a decreasing function of the spin for boson perturbations, whereas the opposite situation appears for fermion ones

Quantification of the secretory glycoproteins of the subcommissural organ by a sensitive sandwich ELISA with a polyclonal antibody and a set of monoclonal antibodies against the bovine Reissner's fiber

The subcommissural organ (SCO) is an ependymal brain gland that releases glycoproteins into the ventricular cerebrospinal fluid where they condense to form the Reissner's fiber (RF). We have developed a highly sensitive and specific two-antibody sandwich enzyme-linked immunosorbent assay (ELISA) for the quantification of the bovine SCO secretory material. The assay was based on the use of the IgG fraction of a polyclonal antiserum against the bovine RF as capture antibody and a pool of three peroxidase-labeled monoclonal antibodies that recognize non-overlapping epitopes of the RF glycoproteins as detection antibody. The detection limit was 1 ng/ml and the working range extended from 1 to 4000 ng/ml. The calibration curve, generated with RF glycoproteins, showed two linear segments: one of low sensitivity, ranging from 1 to 125 ng/ml, and the other of high sensitivity between 125 and 4000 ng/ml. This assay was highly reproducible (mean intra- and interassay coefficient of variation 2.2% and 5.3%, respectively) and its detectability and sensitivity were higher than those of ELISAs using exclusively either polyclonal or monoclonal antibodies against RF glycoproteins. The assay succeeded in detecting and measuring secretory material in crude extracts of bovine SCO, culture medium supernatant of SCO explants and incubation medium of bovine RF; however, soluble secretory material was not detected in bovine cerebrospinal fluid

Making Climate Change Mitigation and Adaptability Real in Africa with Conservation Agriculture

In this report, the authors have gathered essential information on how the agricultural sector can respond to climate change through Conservation Agriculture (CA). This document aims to serve as a basis for decision-making based on science and agricultural experimentation in Africa

Omics data integration facilitates target selection for new antiparasitic drugs against TriTryp infections

Introduction:Trypanosoma cruzi, Trypanosoma brucei, and Leishmania spp., commonly referred to as TriTryps, are a group of protozoan parasites that cause important human diseases affecting millions of people belonging to the most vulnerable populations worldwide. Current treatments have limited efficiencies and can cause serious side effects, so there is an urgent need to develop new control strategies. Presently, the identification and prioritization of appropriate targets can be aided by integrative genomic and computational approaches.Methods: In this work, we conducted a genome-wide multidimensional data integration strategy to prioritize drug targets. We included genomic, transcriptomic, metabolic, and protein structural data sources, to delineate candidate proteins with relevant features for target selection in drug development.Results and Discussion: Our final ranked list includes proteins shared by TriTryps and covers a range of biological functions including essential proteins for parasite survival or growth, oxidative stress-related enzymes, virulence factors, and proteins that are exclusive to these parasites. Our strategy found previously described candidates, which validates our approach as well as new proteins that can be attractive targets to consider during the initial steps of drug discovery

Branching Fractions for D0 -> K+K- and D0 -> pi+pi-, and a Search for CP Violation in D0 Decays

Using the large hadroproduced charm sample collected in experiment E791 at Fermilab, we have measured ratios of branching fractions for the two-body singly-Cabibbo-suppressed charged decays of the D0: (D0 -> KK)/(D0 -> Kpi) = 0.109 +- 0.003 +- 0.003, (D0 -> pipi)/(D0 -> Kpi) = 0.040 +- 0.002 +- 0.003, and (D0 -> KK)/(D0 -> pipi) = 2.75 +- 0.15 +- 0.16. We have looked for differences in the decay rates of D0 and D0bar to the CP eigenstates K+K- and pi+pi-, and have measured the CP asymmetry parameters A_CP(K+K-) = -0.010 +- 0.049 +- 0.012 and A_CP(pi+pi-) = -0.049 +- 0.078 +- 0.030, both consistent with zero.Comment: 10 Postscript pages, including 2 figures. Submitted to Phys. Lett.

The Hydroxamate Siderophore Rhequichelin Is Required for Virulence of the Pathogenic Actinomycete Rhodococcus equi

We previously showed that the facultative intracellular pathogen Rhodococcus equi produces a nondiffusible and catecholate-containing siderophore (rhequibactin) involved in iron acquisition during saprophytic growth. Here, we provide evidence that the rhbABCDE cluster directs the biosynthesis of a hydroxamate siderophore, rhequichelin, that plays a key role in virulence. The rhbC gene encodes a nonribosomal peptide synthetase that is predicted to produce a tetrapeptide consisting of N(5)-formyl-N(5)-hydroxyornithine, serine, N(5)-hydroxyornithine, and N(5)-acyl-N(5)-hydroxyornithine. The other rhb genes encode putative tailoring enzymes mediating modification of ornithine residues incorporated into the hydroxamate product of RhbC. Transcription of rhbC was upregulated during growth in iron-depleted medium, suggesting that it plays a role in iron acquisition. This was confirmed by deletion of rhbCD, rendering the resulting strain R. equi SID2 unable to grow in the presence of the iron chelator 2,2-dipyridyl. Supernatant of the wild-type strain rescued the phenotype of R. equi SID2. The importance of rhequichelin in virulence was highlighted by the rapid increase in transcription levels of rhbC following infection and the inability of R. equi SID2 to grow within macrophages. Unlike the wild-type strain, R. equi SID2 was unable to replicate in vivo and was rapidly cleared from the lungs of infected mice. Rhequichelin is thus a key virulence-associated factor, although nonpathogenic Rhodococcus species also appear to produce rhequichelin or a structurally closely related compound. Rhequichelin biosynthesis may therefore be considered an example of cooption of a core actinobacterial trait in the evolution of R. equi virulence

Direct measurement of the pion valence quark momentum distribution, the pion light-cone wave function squared

We present the first direct measurements of the pion valence quark momentum distribution which is related to the square of the pion light-cone wave function. The measurements were carried out using data on diffractive dissociation of 500 GeV/c $\pi^-$ into di-jets from a platinum target at Fermilab experiment E791. The results show that the $|q\bar {q}>$ light-cone asymptotic wave function, which was developed using perturbative QCD methods, describes the data well for $Q^2 \sim 10 ~{\rm (GeV/c)^2}$ or more. We also measured the transverse momentum distribution of the diffractive di-jets.Comment: 13 pages, 4 figure