Histone acetylations mark origins of polycistronic transcription in Leishmania major

<p>Abstract</p> <p>Background</p> <p>Many components of the RNA polymerase II transcription machinery have been identified in kinetoplastid protozoa, but they diverge substantially from other eukaryotes. Furthermore, protein-coding genes in these organisms lack individual transcriptional regulation, since they are transcribed as long polycistronic units. The transcription initiation sites are assumed to lie within the 'divergent strand-switch' regions at the junction between opposing polycistronic gene clusters. However, the mechanism by which Kinetoplastidae initiate transcription is unclear, and promoter sequences are undefined.</p> <p>Results</p> <p>The chromosomal location of TATA-binding protein (TBP or TRF4), Small Nuclear Activating Protein complex (SNAP₅₀), and H3 histones were assessed in <it>Leishmania major </it>using microarrays hybridized with DNA obtained through chromatin immunoprecipitation (ChIP-chip). The TBP and SNAP₅₀binding patterns were almost identical and high intensity peaks were associated with tRNAs and snRNAs. Only 184 peaks of acetylated H3 histone were found in the entire genome, with substantially higher intensity in rapidly-dividing cells than stationary-phase. The majority of the acetylated H3 peaks were found at divergent strand-switch regions, but some occurred at chromosome ends and within polycistronic gene clusters. Almost all these peaks were associated with lower intensity peaks of TBP/SNAP₅₀binding a few kilobases upstream, evidence that they represent transcription initiation sites.</p> <p>Conclusion</p> <p>The first genome-wide maps of DNA-binding protein occupancy in a kinetoplastid organism suggest that H3 histones at the origins of polycistronic transcription of protein-coding genes are acetylated. Global regulation of transcription initiation may be achieved by modifying the acetylation state of these origins.</p

Spectral library search for improved TMTpro labelled peptide assignment in human plasma proteomics

Funding Information: This work was supported by a research grant from the Danish Cardiovascular Academy, which is funded by the Novo Nordisk Foundation, grant number NNF20SA0067242 and the Danish Heart Foundation. Publisher Copyright: © 2023 The Authors. Proteomics published by Wiley-VCH GmbH.Clinical biomarker discovery is often based on the analysis of human plasma samples. However, the high dynamic range and complexity of plasma pose significant challenges to mass spectrometry-based proteomics. Current methods for improving protein identifications require laborious pre-analytical sample preparation. In this study, we developed and evaluated a TMTpro-specific spectral library for improved protein identification in human plasma proteomics. The library was constructed by LC-MS/MS analysis of highly fractionated TMTpro-tagged human plasma, human cell lysates, and relevant arterial tissues. The library was curated using several quality filters to ensure reliable peptide identifications. Our results show that spectral library searching using the TMTpro spectral library improves the identification of proteins in plasma samples compared to conventional sequence database searching. Protein identifications made by the spectral library search engine demonstrated a high degree of complementarity with the sequence database search engine, indicating the feasibility of increasing the number of protein identifications without additional pre-analytical sample preparation. The TMTpro-specific spectral library provides a resource for future plasma proteomics research and optimization of search algorithms for greater accuracy and speed in protein identifications in human plasma proteomics, and is made publicly available to the research community via ProteomeXchange with identifier PXD042546.publishersversionepub_ahead_of_prin

A posteriori inclusion of parton density functions in NLO QCD final-state calculations at hadron colliders: The APPLGRID Project

A method to facilitate the consistent inclusion of cross-section measurements based on complex final-states from HERA, TEVATRON and the LHC in proton parton density function (PDF) fits has been developed. This can be used to increase the sensitivity of LHC data to deviations from Standard Model predictions. The method stores perturbative coefficients of NLO QCD calculations of final-state observables measured in hadron colliders in look-up tables. This allows the posteriori inclusion of parton density functions (PDFs), and of the strong coupling, as well as the a posteriori variation of the renormalisation and factorisation scales in cross-section calculations. The main novelties in comparison to original work on the subject are the use of higher-order interpolation, which substantially improves the trade-off between accuracy and memory use, and a CPU and computer memory optimised way to construct and store the look-up table using modern software tools. It is demonstrated that a sufficient accuracy on the cross-section calculation can be achieved with reasonably small look-up table size by using the examples of jet production and electro-weak boson (Z, W) production in proton-proton collisions at a center-of-mass energy of 14 TeV at the LHC. The use of this technique in PDF fitting is demonstrated in a PDF-fit to HERA data and simulated LHC jet cross-sections as well as in a study of the jet cross-section uncertainties at various centre-of-mass energies

Community Structure in Congressional Cosponsorship Networks

We study the United States Congress by constructing networks between Members of Congress based on the legislation that they cosponsor. Using the concept of modularity, we identify the community structure of Congressmen, as connected via sponsorship/cosponsorship of the same legislation, to investigate the collaborative communities of legislators in both chambers of Congress. This analysis yields an explicit and conceptually clear measure of political polarization, demonstrating a sharp increase in partisan polarization which preceded and then culminated in the 104th Congress (1995-1996), when Republicans took control of both chambers. Although polarization has since waned in the U.S. Senate, it remains at historically high levels in the House of Representatives.Comment: 8 pages, 4 figures (some with multiple parts), to appear in Physica A; additional background info and explanations added from last versio

Rapid and reversible impairment of episodic memory by a high-fat diet in mice.

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. This work was supported by an EASTBIO BBSRC PhD studentship to F.H.M., L.M.W., C.G., A.C.M., G.W.H. and F.M.C. are supported by Scottish Government’s Rural and Environment Science and Analytical Services Division (RESAS).Peer reviewedPublisher PD

Rapid carbon accumulation in a peatland following Late Holocene tephra deposition, New Zealand

Contemporary measurements of carbon (C) accumulation rates in peatlands around the world often show the C sink to be stronger on average than at times in the past. Alteration of global nutrient cycles could be contributing to elevated carbon accumulation in the present day. Here we examine the effect of volcanic inputs of nutrients on peatland C accumulation in Moanatuatua Bog, New Zealand, by examining a high-resolution Late Holocene C accumulation record during which powerful volcanic eruptions occurred, depositing two visible rhyolitic tephra layers (Taupo, 232 ± 10 CE; Kaharoa, 1314 ± 12 CE). Carbon accumulation rates since c. 50 CE, well before any human presence, increased from a background rate of 23 g C m−2 yr−1 up to 110 g C m−2 yr−1 following the deposition of the Taupo Tephra, and 84 g C m−2 yr−1 following the deposition of the Kaharoa Tephra. Smaller but nevertheless marked increases in C accumulation additionally occurred in association with the deposition of three andesitic-dacitic cryptotephras (each ≤ ∼1 mm thick) of the Tufa Trig Formation between the Taupo and Kaharoa events. These five periods of elevated C uptake, especially those associated with the relatively thick Taupo and Kaharoa tephras, were accompanied by shifts in nutrient stoichiometry, indicating that there was greater availability of phosphorus (P) relative to nitrogen (N) and C during the period of high C uptake. Such P was almost certainly derived from volcanic sources, with P being present in the volcanic glass at Moanatuatua, and many of the eruptions described being associated with the local deposition of the P rich mineral apatite. We found peatland C accumulation to be tightly coupled to N and P accumulation, suggesting nutrient inputs exert a strong control on rates of peat accumulation. Nutrient stoichiometry indicated a strong ability to recover P within the ecosystem, with C:P ratios being higher than most other peatlands in the literature. We conclude that nutrient inputs, deriving from volcanic eruptions, have been very important for C accumulation rates in the past. Therefore, the elevated nutrient inputs occurring in the present day could offer a more plausible explanation, as opposed to a climatic component, for observed high contemporary C accumulation in New Zealand peatlands