PuFFIN--a parameter-free method to build nucleosome maps from paired-end reads.

BackgroundWe introduce a novel method, called PuFFIN, that takes advantage of paired-end short reads to build genome-wide nucleosome maps with larger numbers of detected nucleosomes and higher accuracy than existing tools. In contrast to other approaches that require users to optimize several parameters according to their data (e.g., the maximum allowed nucleosome overlap or legal ranges for the fragment sizes) our algorithm can accurately determine a genome-wide set of non-overlapping nucleosomes without any user-defined parameter. This feature makes PuFFIN significantly easier to use and prevents users from choosing the "wrong" parameters and obtain sub-optimal nucleosome maps.ResultsPuFFIN builds genome-wide nucleosome maps using a multi-scale (or multi-resolution) approach. Our algorithm relies on a set of nucleosome "landscape" functions at different resolution levels: each function represents the likelihood of each genomic location to be occupied by a nucleosome for a particular value of the smoothing parameter. After a set of candidate nucleosomes is computed for each function, PuFFIN produces a consensus set that satisfies non-overlapping constraints and maximizes the number of nucleosomes.ConclusionsWe report comprehensive experimental results that compares PuFFIN with recently published tools (NOrMAL, TEMPLATE FILTERING, and NucPosSimulator) on several synthetic datasets as well as real data for S. cerevisiae and P. falciparum. Experimental results show that our approach produces more accurate nucleosome maps with a higher number of non-overlapping nucleosomes than other tools

Analysis of nucleosome positioning landscapes enables gene discovery in the human malaria parasite Plasmodium falciparum.

BackgroundPlasmodium falciparum, the deadliest malaria-causing parasite, has an extremely AT-rich (80.7 %) genome. Because of high AT-content, sequence-based annotation of genes and functional elements remains challenging. In order to better understand the regulatory network controlling gene expression in the parasite, a more complete genome annotation as well as analysis tools adapted for AT-rich genomes are needed. Recent studies on genome-wide nucleosome positioning in eukaryotes have shown that nucleosome landscapes exhibit regular characteristic patterns at the 5'- and 3'-end of protein and non-protein coding genes. In addition, nucleosome depleted regions can be found near transcription start sites. These unique nucleosome landscape patterns may be exploited for the identification of novel genes. In this paper, we propose a computational approach to discover novel putative genes based exclusively on nucleosome positioning data in the AT-rich genome of P. falciparum.ResultsUsing binary classifiers trained on nucleosome landscapes at the gene boundaries from two independent nucleosome positioning data sets, we were able to detect a total of 231 regions containing putative genes in the genome of Plasmodium falciparum, of which 67 highly confident genes were found in both data sets. Eighty-eight of these 231 newly predicted genes exhibited transcription signal in RNA-Seq data, indicative of active transcription. In addition, 20 out of 21 selected gene candidates were further validated by RT-PCR, and 28 out of the 231 genes showed significant matches using BLASTN against an expressed sequence tag (EST) database. Furthermore, 108 (47%) out of the 231 putative novel genes overlapped with previously identified but unannotated long non-coding RNAs. Collectively, these results provide experimental validation for 163 predicted genes (70.6%). Finally, 73 out of 231 genes were found to be potentially translated based on their signal in polysome-associated RNA-Seq representing transcripts that are actively being translated.ConclusionOur results clearly indicate that nucleosome positioning data contains sufficient information for novel gene discovery. As distinct nucleosome landscapes around genes are found in many other eukaryotic organisms, this methodology could be used to characterize the transcriptome of any organism, especially when coupled with other DNA-based gene finding and experimental methods (e.g., RNA-Seq)

Trans-nasal endoscopic and intra-oral combined approach for odontogenic cysts

Maxillary cysts are a common finding in maxillofacial surgery, dentistry and otolaryngology. Treatment is surgical; a traditional approach includes Caldwell-Luc and other intra-oral approaches. In this article, we analyse the outcomes of 9 patients operated on using a combined intra-oral and trans-nasal approach to the aforementioned disease. Although the number of patients is small, the good results of this study suggest that the combined approach might be a reliable treatment option

DNA-encoded nucleosome occupancy is associated with transcription levels in the human malaria parasite Plasmodium falciparum.

BackgroundIn eukaryotic organisms, packaging of DNA into nucleosomes controls gene expression by regulating access of the promoter to transcription factors. The human malaria parasite Plasmodium falciparum encodes relatively few transcription factors, while extensive nucleosome remodeling occurs during its replicative cycle in red blood cells. These observations point towards an important role of the nucleosome landscape in regulating gene expression. However, the relation between nucleosome positioning and transcriptional activity has thus far not been explored in detail in the parasite.ResultsHere, we analyzed nucleosome positioning in the asexual and sexual stages of the parasite's erythrocytic cycle using chromatin immunoprecipitation of MNase-digested chromatin, followed by next-generation sequencing. We observed a relatively open chromatin structure at the trophozoite and gametocyte stages, consistent with high levels of transcriptional activity in these stages. Nucleosome occupancy of genes and promoter regions were subsequently compared to steady-state mRNA expression levels. Transcript abundance showed a strong inverse correlation with nucleosome occupancy levels in promoter regions. In addition, AT-repeat sequences were strongly unfavorable for nucleosome binding in P. falciparum, and were overrepresented in promoters of highly expressed genes.ConclusionsThe connection between chromatin structure and gene expression in P. falciparum shares similarities with other eukaryotes. However, the remarkable nucleosome dynamics during the erythrocytic stages and the absence of a large variety of transcription factors may indicate that nucleosome binding and remodeling are critical regulators of transcript levels. Moreover, the strong dependency between chromatin structure and DNA sequence suggests that the P. falciparum genome may have been shaped by nucleosome binding preferences. Nucleosome remodeling mechanisms in this deadly parasite could thus provide potent novel anti-malarial targets

Tethered balloon measurements during Arctic autumn conditions in the framework of HALO-(AC)3

The BalloonbornE moduLar Utility for profilinG the lower Atmosphere (BELUGA) was deployed in autumn 2021 in the Arctic at the AWIPEV research station in Ny-Ålesund (Svalbard). In-situ profiles of thermodynamic parameters, broadband radiation, turbulence, aerosol particle concentrations, and cloud microphysical structure, were performed. Additionally, samples of ice nucleating particles were collected. Thermal infrared radiation profiles are presented for different cloud conditions. The data provides the base for studying the vertical distribution of cloud radiative effects, and extends the common view of the bi-modal distribution of the Arctic surface energy budget.Das Fesselballonsystem BalloonbornE moduLar Utility for profilinG the lower Atmosphere (BELUGA) wurde im Herbst 2021 an der Forschungsstation Ny-Ålesund in der Arktis eingesetzt. Es wurden In-situ Profile von thermodynamischen Parametern, breitbandiger Strahlung, Turbulenz, Aerosolpartikelkonzentrationen und der mikrophysikalischer Wolkenstruktur erstellt. Zusätzlich wurden Proben von eiskeimbildenden Partikeln gesammelt. Strahlungsprofile wurden unter verschiedenen Wolkenbedeckungen gemessen und quantifizieren die vertikale Verteilung der Wolkenstrahlungseffekte. Die Profilmessungen erweitern damit die für bodennahe Messungen bekannte modale Verteilung des Energiehaushalts der Arktis

Tethered balloon measurements during Arctic spring conditions in Ny-Ålesund in the framework of HALO-(AC)3

The tethered balloon system BELUGA (BalloonbornE moduLar Utility for profilinG the lower Atmosphere) was operated in spring 2022 at the AWIPEV research station (Ny-Ålesund, Svalbard). In-situ profiles of thermodynamic parameters, thermalinfrared radiation, aerosol particle concentrations, and turbulence, were measured and analyzed. Additionally, samples of ice-nucleating particles were collected at various heights. In combination with previous BELUGA datasets, measurements from this campaign provide a solid base for studying the vertical profiles of the radiative energy budget and heating rates in different atmospheric states in the Arctic lower troposphere. Here, example thermal-infrared radiation profiles are presented for a period of persisting cloudless conditions related to a series of marine cold air outbreaks in late March/early April. Measurements in clouds are analyzed for a developing cloud observed on 6 May and display the impact of cloudiness on radiation profiles.Das Fesselballonsystem BELUGA (BalloonbornE moduLar Utility for profilinG the lowerAtmosphere) wurde im Frühjahr 2022 an der Forschungsstation AWIPEVStation (Ny-Ålesund, Svalbard) eingesetzt. In-situ-Profile von thermodynamischen Parametern, terrestrische Strahlung, Aerosolpartikelkonzentrationen und Turbulenz wurden gemessen und ausgewertet. Zusätzlich wurden in verschiedenen Höhen Proben von eiskeimbildenden Partikeln gesammelt. In Kombination mit früheren BELUGA Messungen zu anderen Jahreszeiten und an anderen arktischen Messstandorten bieten die Messungen in Ny-Ålesund eine Grundlage fürweitereUntersuchungen des Strahlungsenergiehaushalts und des Einflusses vonWolken auf atmosphärische Heizraten. Profile der Strahlungsbilanz werden für eine anhaltende Kälteperiode zwischen Ende März bis Anfang April 2022 vorgestellt. Über diesen Zeitraum herrschten vor allem wolkenlose Bedingungen. Weitere Beobachtungen unter einer sich entwickelnden Wolkendecke am 6. Mai 2022 zeigen den Einfluss der Bewölkung auf die Strahlungsprofile

ThIEF: Finding Genome-wide Trajectories of Epigenetics Marks

We address the problem of comparing multiple genome-wide maps representing nucleosome positions or specific histone marks. These maps can originate from the comparative analysis of ChIP-Seq/MNase-Seq/FAIRE-Seq data for different cell types/tissues or multiple time points. The input to the problem is a set of maps, each of which is a list of genomics locations for nucleosomes or histone marks. The output is an alignment of nucleosomes/histone marks across time points (that we call trajectories), allowing small movements and gaps in some of the maps. We present a tool called ThIEF (TrackIng of Epigenetic Features) that can efficiently compute these trajectories. ThIEF comes into two "flavors": ThIEF:Iterative finds the trajectories progressively using bipartite matching, while ThIEF:LP solves a k-partite matching problem on a hyper graph using linear programming. ThIEF:LP is guaranteed to find the optimal solution, but it is slower than ThIEF:Iterative. We demonstrate the utility of ThIEF by providing an example of applications on the analysis of temporal nucleosome maps for the human malaria parasite. As a surprisingly remarkable result, we show that the output of ThIEF can be used to produce a supervised classifier that can accurately predict the position of stable nucleosomes (i.e., nucleosomes present in all time points) and unstable nucleosomes (i.e., present in at most half of the time points) from the primary DNA sequence. To the best of our knowledge, this is the first result on the prediction of the dynamics of nucleosomes solely based on their DNA binding preference. Software is available at https://github.com/ucrbioinfo/ThIEF

Emetogenicity of Antibody-Drug Conjugates (ADCs) in Solid Tumors with a Focus on Trastuzumab Deruxtecan: Insights from an Italian Expert Panel

In the past decade, nine antibody-drug conjugates (ADCs) have been approved for the treatment of various tumors, four of which specifically for solid malignancies. ADCs deliver the cytotoxic payload to the cancer site, thereby improving chemotherapy efficacy while reducing systemic drug exposure and toxicity. With their high selectivity, ADCs are associated with a manageable side-effect profile, with nausea and vomiting being among the most frequent toxicities, although this may vary according to the respective ADC and the associated payload. Information about the emetic risk of the new ADC compounds is limited. Three virtual focus groups of Italian oncologists were held to raise awareness on the importance of an antiemetic prophylaxis regimen to prevent and mitigate ADC-associated emesis and its sequelae. After reviewing published evidence and guidelines, the three expert panels shared their experience on the early use of ADCs gained through the participation in specific clinical trials and their clinical practice. The following issues were discussed: antiemetic therapy during trastuzumab deruxtecan treatment, with a protocol adopted at the San Raffaele Hospital (Milan, Italy); the use of steroids; the management of anticipatory nausea during trastuzumab deruxtecan therapy; nutritional counselling; and effective doctor\u2013patient communication. The experts acknowledged that recommendations should be drug-specific, and formulated opinion-based advice intended to guide physicians in their daily practice until further evidence emerges

Trans-nasal endoscopic and intra-oral combined approach for odontogenic cysts

Maxillary cysts are a common finding in maxillofacial surgery, dentistry and otolaryngology. Treatment is surgical; a traditional approach includes Caldwell-Luc and other intra-oral approaches. In this article, we analyse the outcomes of 9 patients operated on using a combined intra-oral and trans-nasal approach to the aforementioned disease. Although the number of patients is small, the good results of this study suggest that the combined approach might be a reliable treatment option