Micronuclei induced by reverse transcriptase inhibitors in mononucleated and binucleated cells as assessed by the cytokinesis-block micronucleus assay

This study evaluated the clastogenic and/or aneugenic potential of three nucleoside reverse transcriptase inhibitors (zidovudine - AZT, lamivudine - 3TC and stavudine - d4T) using the cytokinesis-block micronucleus (CBMN) assay in human lymphocyte cultures. All three inhibitors produced a positive response when tested in binucleated cells. The genotoxicity of AZT and 3TC was restricted to binucleated cells since there was no significant increase in the frequency of micronuclei in mononucleated cells. This finding indicated that AZT and 3TC caused chromosomal breakage and that their genotoxicity was related to a clastogenic action. In addition to the positive response observed with d4T in binucleated cells, this drug also increased the frequency of micronuclei in mononucleated cells, indicating clastogenic and aneugenic actions. Since the structural differences between AZT and 3TC and AZT and d4T involve the 3' position in the 2'-deoxyribonucleoside and in an unsaturated 2',3',dideoxyribose, respectively, we suggest that an unsaturated 2', 3', dideoxyribose is responsible for the clastogenic and aneugenic actions of d4T

Macrofossil evidence for a rapid and severe Cretaceous–Paleogene mass extinction in Antarctica

Debate continues about the nature of the Cretaceous–Paleogene (K–Pg) mass extinction event. An abrupt crisis triggered by a bolide impact contrasts with ideas of a more gradual extinction involving flood volcanism or climatic changes. Evidence from high latitudes has also been used to suggest that the severity of the extinction decreased from low latitudes towards the poles. Here we present a record of the K–Pg extinction based on extensive assemblages of marine macrofossils (primarily new data from benthic molluscs) from a highly expanded Cretaceous–Paleogene succession: the López de Bertodano Formation of Seymour Island, Antarctica. We show that the extinction was rapid and severe in Antarctica, with no significant biotic decline during the latest Cretaceous, contrary to previous studies. These data are consistent with a catastrophic driver for the extinction, such as bolide impact, rather than a significant contribution from Deccan Traps volcanism during the late Maastrichtian

A Mouse Model of Pulmonary Metastasis from Spontaneous Osteosarcoma Monitored In Vivo by Luciferase Imaging

BACKGROUND: Osteosarcoma (OSA) is lethal when metastatic after chemotherapy and/or surgical treatment. Thus animal models are necessary to study the OSA metastatic spread and to validate novel therapies able to control the systemic disease. We report the development of a syngeneic (Balb/c) murine OSA model, using a cell line derived from a spontaneous murine tumor. METHODOLOGY: The tumorigenic and metastatic ability of OSA cell lines were assayed after orthotopic injection in mice distal femur. Expression profiling was carried out to characterize the parental and metastatic cell lines. Cells from metastases were propagated and engineered to express Luciferase, in order to follow metastases in vivo. PRINCIPAL FINDINGS: Luciferase bioluminescence allowed to monitor the primary tumor growth and revealed the appearance of spontaneous pulmonary metastases. In vivo assays showed that metastasis is a stable property of metastatic OSA cell lines after both propagation in culture and luciferase trasduction. When compared to parental cell line, both unmodified and genetically marked metastatic cells, showed comparable and stable differential expression of the enpp4, pfn2 and prkcd genes, already associated to the metastatic phenotype in human cancer. CONCLUSIONS: This OSA animal model faithfully recapitulates some of the most important features of the human malignancy, such as lung metastatization. Moreover, the non-invasive imaging allows monitoring the tumor progression in living mice. A great asset of this model is the metastatic phenotype, which is a stable property, not modifiable after genetic manipulation

Understanding Growth and Malnutrition in Baka Pygmy Children

We determined stunting, wasting, and obesity frequencies in a total 1092 2-to-12 year old Baka Pygmy children from anthropometric and health data gathered in 34 villages in the Djoum-Mintom region in southeastern Cameroon in four health campaigns in 2010 and 2017–9. We compare these to the WHO Child Growth Standards, Amazonian Tsiname growth references for inter-population comparisons and the study population itself. Population-specific growth charts were constructed using GAMLSS modelling. Our results show that Baka children have one of the highest global rates of stunting relative to the WHO child growth standard with 57.8% for 2-to-12 year olds and 64% and 73% for 2-to-4 year old girls and boys, respectively. Frequencies of wasting, overweight, and low BMI were low at 3.4%, 4.6% and 4.3%, respectively, for 2-to-12 year olds. Underweight was at 25.5%, in the upper range for sub-Saharan Africa. Edemas indicated rare severe malnutrition (0.3%). Uncertainties in age estimation had dramatic effects on the reliability of estimated individual z-scores but distributions of z-scores were robust at a population level. In the context of the recent evidence for genetic adaptation of the Pygmies’ small stature to the tropical forest environment we argue that WHO child standards for weight and BMI are applicable. However, standards for height are clearly not adequate for Pygmy people. To achieve UN Sustainable Development Goals, we recommend that Pygmy specific growth standards are developed for the various, genetically differing Pygmy tribes

The taxonomy and palaeobiogeography of small chorate dinoflagellate cysts from the Late Cretaceous to Quaternary of Antarctica

Small chorate dinoflagellate cysts are common in Upper Cretaceous to Quaternary sedimentary successions around the Antarctic margin. Taxonomic confusion surrounding dinoflagellate cysts and acritarchs of similar morphology throughout the southern high palaeolatitudes has hitherto limited investigation of their palaeoecological significance. This study aims to solve the taxonomic problems, and to allow a new assessment of dinoflagellate cyst acmes. A detailed morphological study of new material from the López de Bertodano Formation of Seymour Island, Antarctic Peninsula, is presented. These dinoflagellate cysts are identified as Impletosphaeridium clavusWrenn & Hart 1988 emend. nov. Their gross morphology and their vast abundances in the James Ross Basin are strongly suggestive of dinoflagellate blooms. This scenario implies similarities to modern dinoflagellate cysts from the polar regions

Population biology of Streptococcus pneumoniae in West Africa: multilocus sequence typing of serotypes that exhibit different predisposition to invasive disease and carriage.

BACKGROUND: Little is known about the population biology of Streptococcus pneumoniae in developing countries, although the majority of pneumococcal infections occur in this setting. The aim of the study was to apply MLST to investigate the population biology of S. pneumoniae in West Africa. METHODS: Seventy three invasive and carriage S. pneumoniae isolates from three West African countries including The Gambia, Nigeria and Ghana were investigated. The isolates covered seven serotypes (1, 3, 5, 6A, 11, 14, 23F) and were subjected to multilocus sequence typing and antibiotic susceptibility testing. RESULTS: Overall, 50 different sequence types (STs) were identified, of which 38% (29) were novel. The most common ST was a novel clone-ST 4012 (6.5%), and some clones including STs 913, 925, 1737, 2160 and 3310 appeared to be specific to the study region. Two STs including ST 63 and ST 4012 were associated with multiple serotypes indicating a history of serotype switching. ST 63 was associated with serotypes 3 and 23F, while ST 4012 was associated with serotypes 6A and 23. eBURST analyses using the stringent 6/7 identical loci definition grouped the 50 STs into 5 clonal complexes and 65 singletons, expressing a high level of genetic diversity among the isolates. Compared to the other serotypes, serotypes 1 and 5 isolates appeared to be more clonal. Internationally recognized antibiotic resistant clones of S. pneumoniae were generally absent in the population investigated and the only multidrug resistant isolate identified (1/66) belong to the Pneumocococcal Epidemiology Network clone ST 63. CONCLUSIONS: The pneumococcal population in West Africa is quite divergent, and serotypes that are common in invasive disease (such as serotypes 1 and 5) are more likely to be clonal than serotypes that are common in carriage

Different miRNA profiles in plasma derived small and large extracellular vesicles of neurodegenerative disease patients.

Identifying biomarkers is essential for early diagnosis of neurodegenerative diseases (NDs). Large (LEVs) and small extracellular vesicles (SEVs) are extracellular vesicles (EVs) of different sizes and biological functions transported in blood and they may be valid biomarkers for NDs. The aim of our study was to investigate common and different miRNA signatures in plasma derived LEVs and SEVs of Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic Lateral Sclerosis (ALS) and Fronto‐Temporal Dementia (FTD) patients. LEVs and SEVs were isolated from plasma of patients and healthy volunteers (CTR) by filtration and differential centrifugation and RNA was extracted. Small RNAs libraries were carried out by Next Generation Sequencing (NGS). MiRNAs discriminate all NDs diseases from CTRs and they can provide a signature for each NDs. Common enriched pathways for SEVs were instead linked to ubiquitin mediated proteolysis and Toll‐like receptor signaling pathways and for LEVs to neurotrophin signaling and Glycosphingolipid biosynthesis pathway. LEVs and SEVs are involved in different pathways and this might give a specificity to their role in the spreading of the disease. The study of common and different miRNAs transported by LEVs and SEVs can be of great interest for biomarker discovery and for pathogenesis studies in neurodegeneration