Exploratory analysis of transposable elements expression in the C. elegans early embryo

Background: Transposable Elements (TE) are mobile sequences that make up large portions of eukaryote genomes. The functions they play within the complex cellular architecture are still not clearly understood, but it is becoming evident that TE have a role in several physiological and pathological processes. In particular, it has been shown that TE transcription is necessary for the correct development of mice embryos and that their expression is able to finely modulate transcription of coding and non-coding genes. Moreover, their activity in the central nervous system (CNS) and other tissues has been correlated with the creation of somatic mosaicisms and with pathologies such as neurodevelopmental and neurodegenerative diseases as well as cancers. Results: We analyzed TE expression among different cell types of the Caenorhabditis elegans (C. elegans) early embryo asking if, where and when TE are expressed and whether their expression is correlated with genes playing a role in early embryo development. To answer these questions, we took advantage of a public C. elegans embryonic single-cell RNA-seq (sc-RNAseq) dataset and developed a bioinformatics pipeline able to quantify reads mapping specifically against TE, avoiding counting reads mapping on TE fragments embedded in coding/non-coding transcripts. Our results suggest that i) canonical TE expression analysis tools, which do not discard reads mapping on TE fragments embedded in annotated transcripts, may over-estimate TE expression levels, ii) Long Terminal Repeats (LTR) elements are mostly expressed in undifferentiated cells and might play a role in pluripotency maintenance and activation of the innate immune response, iii) non-LTR are expressed in differentiated cells, in particular in neurons and nervous system-Associated tissues, and iv) DNA TE are homogenously expressed throughout the C. elegans early embryo development. Conclusions: TE expression appears finely modulated in the C. elegans early embryo and different TE classes are expressed in different cell types and stages, suggesting that TE might play diverse functions during early embryo development

Induction of Isochromanones by Co-Cultivation of the Marine Fungus Cosmospora sp. and the Phytopathogen Magnaporthe oryzae

Microbial co-cultivation is a promising approach for the activation of biosynthetic gene clusters (BGCs) that remain transcriptionally silent under artificial culture conditions. As part of our project aiming at the discovery of marine-derived fungal agrochemicals, we previously used four phytopathogens as model competitors in the co-cultivation of 21 marine fungal strains. Based on comparative untargeted metabolomics analyses and anti-phytopathogenic activities of the co-cultures, we selected the co-culture of marine Cosmospora sp. with the phytopathogen Magnaporthe oryzae for in-depth chemical studies. UPLC-MS/MS-based molecular networking (MN) of the co-culture extract revealed an enhanced diversity of compounds in several molecular families, including isochromanones, specifically induced in the co-culture. Large scale co-cultivation of Cosmospora sp. and M. oryzae resulted in the isolation of five isochromanones from the whole co-culture extract, namely the known soudanones A, E, D (1-3) and their two new derivatives, soudanones H-I (4-5), the known isochromans, pseudoanguillosporins A and B (6, 7), naphtho-γ-pyrones, cephalochromin and ustilaginoidin G (8, 9), and ergosterol (10). Their structures were established by NMR, HR-ESIMS, FT-IR, electronic circular dichroism (ECD) spectroscopy, polarimetry ([α]D), and Mosher’s ester reaction. Bioactivity assays revealed antimicrobial activity of compounds 2 and 3 against the phytopathogens M. oryzae and Phytophthora infestans, while pseudoanguillosporin A (6) showed the broadest and strongest anti-phytopathogenic activity against Pseudomonas syringae, Xanthomonas campestris, M. oryzae and P. infestans. This is the first study assessing the anti-phytopathogenic activities of soudanones

Combined treatment with amphotericin-B and granulocyte transfusion from G-CSF-stimulated donors in an aplastic patient with invasive aspergillosis undergoing bone marrow transplantation.

Granulocyte transfusions from G-CSF stimulated donors were added to standard anti-infective treatment in preparation for and during allogeneic bone marrow transplantation in a young man affected by very severe acute aplastic anemia and invasive aspergillosis. Nine concentrates with a mean neutrophil content of 18.7x109/L (2.6x 108/kg patient b.w.) were transfused before and after marrow infusion. An impressive clinical improvement was noticed after each granulocyte transfusion, although this was not always paralleled by a neutrophil increase in the peripheral blood. Engraftment (N>0.5x109/L and PIt >25x109/L) was verified at +16 and +40 days, respectively. The patient is currently in complete hematological and microbiological remission 14 months after transplantation. Granulocyte apheresis from G-CSF stimulated donors provides a high number of activated neutrophils. At the dose given (300 μg/day) donor tolerance to G-CSF was excellent. This new approach is indicated when life-threatening infections develop in patients exposed to prolonged severe neutropenia

S50-01 Depression and bipolar disorder: Is prevention of mania possible? Critical issues on diagnostic criteria

Diagnostic criteria for bipolar disorder in DSM IV require the occurrence of a manic or hypomanic episode. The scant appropriateness of these criteria compared with Kraepelin"s concept of manic depressive insanity has been repeatedly reported and the concept of bipolar spectrum has been proposed for more than 30 years. The negative consequences of pure adherence to operational diagnostic criteria on clinical needs are presented in terms of community epidemiology results and in terms of clinical evidences and the inadequate treatment of depressive and anxiety episodes and the risk of manic switch with antidepressant drugs are discussed.The epidemiological survey conducted in Sesto Fiorentino showed that depressive episodes in patients with subthreshold mania or hypomania were different from the clinical presentation of pure unipolar depressives episodes confirming not only the numeric impact but also qualitative differences between these groups of patients.Our clinical study where predictors of mania have been prospectively evaluated in a trans nosographic sample of outpatients demonstrated that aspects related to bipolarity predicted manic shift regardless of the diagnosis. DSM IV criteria seem not to be able to detect and describe a group of patients relevant both on epidemiological and on clinical level. These findings underline the need of a careful examination of patients treatment and validate the rule of further research in definition of mood disorders boundaries for prevention strategies

Stable Catechol Keto Tautomers in Cytotoxic Heterodimeric Cyclic Diarylheptanoids from the Seagrass Zostera marina

Two diarylheptanoid heterodimers, zosterabisphenones A (1) and B (2), were isolated from the seagrass Zostera marina. They feature unprecedented catechol keto tautomers, stable because of steric constraints. Their structure elucidation was based on extensive low-temperature NMR studies and ECD and MS data, with the essential aid of DFT prediction of NMR and ECD spectra. Zosterabisphenone B (2) was selectively cytotoxic against the adenocarcinoma colon cancer cell line HCT116 with IC50 3.6 ± 1.1 μM at 48 h

A Reliable and Cost-Efficient PCR-RFLP Tool for the Rapid Identification of Cetaceans in the Mediterranean Sea

Twenty-five species of cetaceans have been reported throughout the Mediterranean Sea, eight of them are commonly distributed in the whole basin and are regularly found beached or adrift in the sea. Stranded animals are frequently found in poor conservation status, preventing reliable identification; identification is thus often based solely on morphological features. Therewith, molecular tools are especially useful to provide taxonomic identification. In this work, a four-enzymes PCR-RFLP in silico protocol, based on a fragment of the mitochondrial gene cytb, has been designed for cetacean species occurring in the Mediterranean Sea. Moreover, beached or floating specimen samples belonging to the eight common species have been tested in the laboratory, providing evidence that this approach represents a reliable, cost- and time-effective tool for their specific identification

Monitoring cyanobacterial blooms during the COVID-19 pandemic in Campania, Italy: The case of lake avernus

Cyanobacteria are ubiquitous photosynthetic microorganisms considered as important contributors to the formation of Earth’s atmosphere and to the process of nitrogen fixation. However, they are also frequently associated with toxic blooms, named cyanobacterial harmful algal blooms (cyanoHABs). This paper reports on an unusual out-of-season cyanoHAB and its dynamics during the COVID-19 pandemic, in Lake Avernus, South Italy. Fast detection strategy (FDS) was used to assess this phenomenon, through the integration of satellite imagery and biomolecular investigation of the environmental samples. Data obtained unveiled a widespread Microcystis sp. bloom in February 2020 (i.e., winter season in Italy), which completely disappeared at the end of the following COVID-19 lockdown, when almost all urban activities were suspended. Due to potential harmfulness of cyanoHABs, crude extracts from the “winter bloom” were evaluated for their cytotoxicity in two different human cell lines, namely normal dermal fibroblasts (NHDF) and breast adenocarcinoma cells (MCF-7). The chloroform extract was shown to exert the highest cytotoxic activity, which has been correlated to the presence of cyanotoxins, i.e., microcystins, micropeptins, anabaenopeptins, and aeruginopeptins, detected by molecular networking analysis of liquid chromatography tandem mass spectrometry (LC-MS/MS) data

Isolation of Isotrichophycin C and Trichophycins G–I from a Collection of Trichodesmium thiebautii

The trichophycin family of compounds are chlorinated polyketides first discovered from environmental collections of a bloom-forming Trichodesmium sp. cyanobacterium. In an effort to fully capture the chemical space of this group of metabolites, the utilization of MS/MS-based molecular networking of a Trichodesmium thiebautii extract revealed a metabolome replete with halogenated compounds. Subsequent MS-guided isolation resulted in the characterization of isotrichophycin C and trichophycins G–I (1–4). These new metabolites had intriguing structural variations from those trichophycins previously characterized, which allowed for a comparative study to examine structural features that are associated with toxicity to murine neuroblastoma cells. Additionally, we propose the absolute configuration of the previously characterized trichophycin A (5). Overall, the metabolome of the Trichodesmium bloom is hallmarked by an unprecedented amount of chlorinated molecules, many of which remain to be structurally characterized